Greening the Oxidation of Borneol to Camphor

Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory

Notes to Instructors: Greening the Oxidation of Borneol to Camphor Introduction Oxidation reactions are an essential component of undergraduate organic chemistry laboratory curricula. The oxidation of primary or secondary alcohols, to produce an aldehyde or ketone, is a functional group transformation that can serve as the gateway linking first semester discussions of alkene reactivity to the myriad of transformations possible for carbonyl compounds. Students can begin to solve and propose multistep syntheses once this crucial link is established. While selectivity and strength of various oxidants are of paramount importance in the lecture, such that the desired compound is hypothetically prepared, students are traditionally trained to focus on the effectiveness, percent yield and percent recovery of these oxidations. Students are not being challenged to consider alternate reaction schemes or the energy required, solvent used, waste generated in the organic chemistry laboratory. Considerations of waste, hazards and safety should be as integral to the design of a reaction as issues of selectivity, effectiveness, percent yield, time and money, in the teaching laboratory. The number of chemistry or chemistry related graduates who are ignorant to the ultimate fate of laboratory waste is unacceptable. Greened laboratory experiments, have provided opportunities to present many of the integral but lacking components of chemistry laboratory instruction, however, we argue that students should be challenged further to engage their creativity in the greening process. With this in mind, we describe below a laboratory experience that challenges students to green a procedure in real-time with the 12 principles as their guideline, without adding an additional laboratory exercise to the already full curriculum. It has been our experience that there are two phases of greening a experiment; first the identification of greenest reagent that can accomplish the transformation with desired selectivity, and second all steps involved with the transformation of the starting material to the pure desired product - methods of reaction, isolation, purification and characterization . These two phases are not mutually exclusive as the choice of the reagent dictates the subsequent steps. However, the two phases are distinct and can be separated into two discrete learning experiences. While most students enrolled in Sophomore level Organic Chemistry may lack the knowledge and skills to identify, locate and apply alternate reaction schemes for a desired transformation, most are readily able to successfully evaluate the “greenness” of several procedures with the assistance of a rubric through a guided–inquiry process. Alternatively, at the traditional stage oxidation laboratories are performed - the beginning of second semester, students are able to begin making informed decisions, engage the greening process and test multiple hypotheses in a more open-inquiry experience given a significantly detailed scaffold. One student in a single laboratory period may not be able to accomplish a noticeable greening, several seemingly simplistic ideas from a cohort of students when coupled together, result in the dramatic cumulative greening experience for the entire class. Community based social networking software, such as Wikis, greatly facilitate the sharing of information. Students gain from learning of successful improvements in real-time from their peers, fostering a level of excitement and challenge not often observed in the organic chemistry laboratory. Herein, we describe two inquiry-based laboratory experiences based upon the oxidation of borneol to camphor. The first guided-inquiry, experience leads students through the comparison of three different procedures, using a rubric and other green metrics. Students, first evaluate the ‘greenness’ of the procedures with a rubric that enables the comparison of the oxidant/reactants, as well as the solvent and energies required for the reaction, and the isolation and purification of the final product. The primary benefit of beginning with the simplistic rubric that we have developed is in its ease of use. The rubric serves as an introduction to quantifying the ‘greenness’ of a procedure, before students perform the detailed calculations of the standard green metrics that are currently in use. The guided-inquiry experience can be adopted as a stand alone laboratory or a pre-lab preparation for the second experience. The open-inquiry laboratory experience provides a scaffold for students to become involved within the greening process. The experiment is designed such that a single improvement can drive the learning experience, while simultaneously encouraging the accumulation of data from lab to lab or year to year to approach the greenest method asymptotically. We have experienced that the experiment collectively supplements the learning objectives of the original laboratory exercise, the oxidation of borneol to camphor, without the aid of direct influence of the instructor. Over the course of three years, students independently designed heterogeneous and homogeneous reactions, tested the catalytic nature of the oxidant, questioned and learned the need for in-process monitoring as well as reactor design and alternative energy sources, designed solvent-free reactions, isolations and purifications, without the need for specific detailed instructions. We also share what the collective has deemed the greenest method to oxidize borneol to camphor to date, as well as several iterations of the procedure along the way to facilitate adoption at any stage of development and the creation of any number of

1


guided-inquiry experiences. Our final “greenest” procedure enables the oxidation of borneol to camphor, in the complete absence of solvent throughout the synthesis, isolation and purification steps, while utilizing a less hazardous solid-supported oxidant in less than 15 minutes. While the aforementioned procedure serves as an excellent in-class demonstration, we strongly encourage the adoption of the pedagogy to involve students in the decision making process with a “less-than, green procedure” in the laboratory to have the largest impact and student engagement with the material We have witnessed that the open-inquiry laboratory described herein, encourages students to further explore the field and recognize that informed decisions must be made throughout the entire process of designing not only the reaction itself, but also in the isolation, purification and characterization in the laboratory.

Background Hazardous and inefficient techniques have been applied to perform oxidation reactions in many undergraduate organic laboratories. Organic chemists have showcased the conversion of toluene to benzoic acid using a boiling aqueous solution of KMnO4, a reaction known to produce extremely low yields (15% or less), as recently as 1997. Choosing to work with milder oxidative conditions, many laboratories switched to the oxidation of an alcohol to a ketone, presently a mainstay of the organic laboratory curriculum as delineated by several organic laboratory textbooks. While earlier editions of this experiment use pyridinium chloro chromate, or sodium dichromate as the oxidant more recent versions employ a more environmentallysensitive reagent: sodium hypochlorite (bleach), or calcium hypochlorite. Intermediate versions included the use of alternative oxidants (TEMPO/ KBr/bleach) or hydrogenised chromium reagents. The carcinogenicity and potent toxicity of chromium VI lead to the development of the sodium hypochlorite procedures, however, the process is still far from green. Commercial chlorine bleach contains detectable quantities of mercury and is a corrosive reagent, which may release chlorine upon reaction with acid. As a starting point, we located alternate reaction schemes that utilized a safer oxidant, required minimal solvent and required minimal energy use during the reaction and as such would produce less waste, while being accomplished within a laboratory period. A procedure utilizing a solid-supported oxidant, in which the oxidant is bound to or absorbed upon the surface of a solid support, could eliminate solvent use and safely utilize a better heating system, such as microwave heat. Additionally, solid-supported oxidants are often easier to handle, facile to remove from reaction mixtures by filtration or centrifugation and safer to dispose of as waste. Several more benign solid-supported and phase-transfer oxidants to convert secondary alcohols to ketones are available and have been utilized in teaching laboratories, however, we began with those oxidants used successfully in conjunction with microwave heating, in the absence of solvent. The procedures of Varma, et al. using the following oxidants provided a well established starting point: clayfen, clay-cop/hydrogen peroxide, chromium trioxide impregnated on wet alumina, iodosylbenzene diacetate on alumina and activated manganese dioxide (AMD) on silica. Each of the five identified procedures utilized identical solvents and energy requirements for the reaction, isolation and purification, therefore, the hazards of working with each oxidant/reactant could be qualitatively evaluated and directly compared. The need to compare the greenness of the procedures lead to the development of a rubric to evaluate and compare the hazards, risks, and safety involved in each. Not surprisingly, students were more concerned over hazards, risks and the safety involved in each proposed procedure than they were with the efficiencies. As the current green metrics focus heavily on efficiencies, the students designed a rubric to focus more heavily on the assessment of the hazards involved with a given procedure, before deciding to calculate the standard green metrics. Our student-designed, rubric first requires the calculation of a ‘Green-Index-Value’ for the oxidant, reagents and solvents involved in the reaction, isolation and purification steps, of an experiment. Calculation of the ‘Green-Index-Value’ enables the semi-quantitative ranking of all chemicals based upon the National Fire Protection Association (NFPA) Rating (Health + Fire + Reactivity)) and the number of “Risk” and “Safety Phrases” listed in the Regulatory Information section of a materials safety data sheet (MSDS), see Figure 1 for an example. Second our rubric also considers the energy involved in the reaction, isolation and purification steps, as well as the purification method itself. The flaw in the rubric’s current design is that all risks and safety phrases are given equal weight. Obviously, Risk Phrase 22 (R22) (harmful if swallowed) ideally should not be equated with R45 (may cause cancer) or R46 (may cause heritable genetic damage). More in depth analysis and evaluation should consider the USNLM’s Toxicology Data Network1 and NIOSH’s documentation for immediately dangerous to life or health (IDLH) concentrations.2 The chemicals utilized in each experiment account for 80% of the total rubric evaluation. The remaining 20% pertains to the energy and purification methods used and significantly more qualitative. The higher the overall rubric score the deeper the “shade of green,” for an evaluated reaction scheme. 1 2

United States National Library of Medicine Toxicology Data Network: http://toxnet.nlm.nih.gov/ (accessed June 2007). National Institute for Occupational Health and Safety (NIOSH) documentation for immediately dangerous to life or health concentrations (IDLH): NIOSH Chemical Listing and Documentation of Revised IDLH Values (as of 3/1/95), http://www.cdc.gov/niosh/idlh/ intridl4.html (accessed June 2007).

2

Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory General Rubric: Procedure Oxidant / Reactants* Solvent* reaction isolation purification Energy

reaction isolation purification

Purification Method

Details GIV = 20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements) or GIV-F GIV = 20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements) or GIV-F GIV = 20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements) or GIV-F GIV = 20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements) or GIV-F “Brown” (0 – 1) “Green” (2 – 3) “Greener” (4 – 5) Ceramic hot-plate, heating manifold, Ceramic hot-plate, heating manifold, Microwave energy, minimal or Bunsen-burner: long heating time. Bunsen-burner: short heating time. no heating. Ceramic hot-plate, heating manifold, Ceramic hot-plate, heating manifold, Microwave energy, minimal or Bunsen-burner: long heating time. Bunsen-burner: short heating time. no heating. Ceramic hot-plate, heating manifold, Ceramic hot-plate, heating manifold, Microwave energy, minimal or Bunsen-burner: long heating time. Bunsen-burner: short heating time. no heating. e.g. column chromatography e.g. distillation e.g. crystallization/sublimation

Total Score

Score #/20 #/20 #/20 #/20 #/5 #/5 #/5 #/5 #/100

*The oxidant / reactant / solvent with the lowest number is included in rubric evaluation for that category.

The current form of the rubric is more quantitative than the initial rubric in which the first five alternative procedures were analyzed, however, re-evaluation of each of the five procedures is provided below for the purposes of instruction. The end result of evaluating the procedures with the rubric described above leads to the same conclusion – the active manganese dioxide adsorbed on silica gel is the least hazardous procedure. Five alternative oxidation procedures: 1. Clayfen The experimental procedure involves a simple mixing of neat alcohol with clayfen and irradiating the reaction mixtures in a microwave oven for 1560 seconds in the absence of any solvent. Clayfen (0.125 g) was thoroughly mixed with neat borneol (0.106 g) in the solid state using a vortex mixer and the material was placed in an alumina bath inside the MW oven and irradiated. Upon completion of the reaction, monitored on TLC (CH2Cl2 : CH 3OH), the product was extracted into CH2Cl2 dried over anhydrous sodium sulfate and purified by vacuum sublimation with an aspirator. 2. Claycop (Copper(II) nitrate on clay)/Hydrogen Peroxide: The experimental procedure involves a simple mixing of neat substrates with claycop (0.46 g per mmol of the substrate) followed by the addition of 30% H2O2 (0.1 mL) in an open container. The mixture is placed in an alumina bath inside a microwave oven and is irradiated for 15-90 sec in the solid state. Upon completion of the reaction, monitored on TLC (CH2Cl2 : CH3OH), the product was extracted into CH2Cl2 dried over anhydrous sodium sulfate and purified by vacuum sublimation with an aspirator 3. Wet Alumina Supported Chromium (VI) Oxide: Wet-alumina is prepared by shaking neutral aluminum oxide (10 g, Aldrich, Brockmann I, ~150 mesh) with distilled water (2 mL). The reagent is prepared by mixing CrO3 (0.8 g) with wet-alumina (2.4 g) using pestle and mortar. This reagent is gradually added to the borneol (0.432 g,) and mixed with a spatula. An exothermic reaction ensues with darkening of the orange color of the reagent and is completed almost immediately as confirmed by TLC (hexane: AcOEt, 8:2). In some cases, brief microwave irradiation (inside an alumina bath is an unmodified household microwave oven) completed the reaction. The product is extracted into CH2Cl2 (2x25 mL) and is passed through a small bed of alumina (1 cm) to afford camphor. The CH2Cl2 solution was dried over anhydrous sodium sulfate and purified by vacuum sublimation with an aspirator 4. Iodobenzene Diacetate on Alumina: Borneol (0.108 g) and IBD (0.355 g) doped on neutral alumina (1 g) are mixed thoroughly on a vortex mixer. The reaction mixture is placed in an alumina bath inside an unmodified household microwave oven and irradiated for a period of 1 min. On completion of the reaction, followed by TLC examination (hexane: AcOEt, 9:1, v/v), the product is extracted into dichloromethane and is neutralized with aqueous sodium bicarbonate solution. Upon completion of the reaction, monitored on TLC (CH2Cl2 : CH3OH), the product was extracted into CH2Cl2 dried over anhydrous sodium sulfate and purified by vacuum sublimation with an aspirator

Clayfen Oxidant/Reactants Solvent

reaction isolation purification Energy reaction isolation purification Purification Method Claycop Oxidant/Reactants Solvent

reaction isolation purification Energy reaction isolation purification Purification Method Wet CrO 3 - Al2O 3 Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method IBD - Al2O3 Oxidant/Reactants Solvent

reaction isolation purification Energy reaction isolation purification Purification Method

Details Clayfen (produces NO2 and NO gasses) (20-19) none CH2Cl2 (20-9), anhyd. Na2SO4 (20-4) none microwave none sublimation sublimation Total Score

Score 1/20 20/20 11/20 20/20 5/5 5/5 3/5 5/5 70/100

Details Claycop (produces NO2 and NO gasses) (20-19) 30% H2O2 (20-11) none CH2Cl2 (20-9), anhyd. Na2SO4 (20-4) none microwave none sublimation sublimation Total Score

Score 1/20 20/20 11/20 20/20 5/5 5/5 3/5 5/5 70/100

Details alumina (20-1), CrO3 (20-26) none CH2Cl2 (20-9), anhyd. Na2SO4 (20-4) none room temp. or microwave none sublimation sublimation Total Score

Score -6/20 20/20 11/20 20/20 5/5 5/5 3/5 5/5 63/100

Details iodobenzene diacetate (20-8), alumina (20-1) none CH2Cl2 (20-9), anhyd. Na2SO4 (20-4) none microwave none sublimation sublimation Total Score

Score 12/20 20/20 11/20 20/20 5/5 5/5 3/5 5/5 81/100

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Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory 5. Active Manganese Dioxide on Silica Add “active” MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.154 g, 1 mmol) to a pestle. Grind with the mortar until a homogenous mixture of borneol in AMD-silica is obtained. Transfer this sample into a glass scintillation vial. Cap the vessel and place in the center of a microwave. Microwave at maximal intensity for 100 s. Remove the hot vial carefully. Once the glass is cool remove the cap. Upon completion of the reaction, monitored on TLC (CH2 Cl2 : CH3OH), the product was extracted into CH2Cl2 dried over anhydrous sodium sulfate and purified by vacuum sublimation with an aspirator

AMD on Silica Oxidant/Reactants

Details active manganese dioxide (20-6), silica (20-0) none CH2Cl2 (20-9), anhyd. Na2SO4 (20-4) none microwave none sublimation sublimation Total Score

Solvent

reaction isolation purification Energy reaction isolation purification Purification Method

Score 14/20 20/20 11/20 20/20 5/5 5/5 3/5 5/5 83/100

The complete procedure, estimated lab time, materials, waste collection and disposal, experimental tips and safety concerns and rubric, green metric and economic analysis for the standard sodium dichromate, sodium hypochlorite and two different iterations of the active manganese dioxide on silica experiments are provided below. To calculate the effective mass yield of each synthetic pathway all materials need to be classified as benign or non-benign. We have calculated the ‘Green Index Value’ for all standard laboratory solvents and have used the values to classify each solvent according to four general classes, by the level of hazard and two categories, benign or non-benign. From the set of data on the following page, we suggest that chemicals with a Green Index Value below of 13 or below be considered non-benign for the purposes of the effective mass yield calculation.

Reagents

GIV-F

Level of Hazard

Benign / Non-Benign

tert-butyl alcohol, ethylene glycol

17

minimal

benign

DMSO, ethanol

16

minimal

benign

ethyl acetate, ethyl methyl ketone

15

minimal

benign

acetone, HMPA

14

minimal

benign

diglyme, N,N-dimethylacetamide, 2-propanol, THF, xylenes

13

moderate

non-benign

acetonitrile, chlorobenzene, diethyl ether, DMF, hexanes, methyl isobutyl ketone, nitromethane, pyridine

12

moderate

non-benign

BHT, 1,2-dichloroethane, 1,2-dimethoxyethane, n-pentane

11

moderate

non-benign

acetic acid (glacial), chloroform, dichloromethane

10

moderate

non-benign

cyclohexane, heptane

9

moderate

non-benign

1,4-dioxane, methanol, toluene

8

moderate

non-benign

benzene, petroleum ether, triethylamine

7

extreme

non-benign

ethylene diamine

6

extreme

non-benign

n-hexane

5

extreme

non-benign

formaldehyde

4

extreme

non-benign

3

extreme

non-benign

2

maximum

non-benign

carbon tetrachloride

4


3 4

Reagents

CAS #

https://fscimage.fishersci.com/msds/

GIV

GIV-F

acetone

[67-64-1]

00140.htm

20-(1-3-0)-(4)-(3)=9

20-(1-×-0)-(3)-(2)=14

acetic acid (glacial)

[64-19-7]

00120.htm

20-(3-2-0)-(2)-(3)=10

acetonitrile

[75-05-8]

00170.htm

20-(2-3-0)-(5)-(3)=7

benzene

[71-43-2]

02610.htm

20-(2-3-0)-(10)-(2)=3

20-(2-×-0)-(9)-(2)=7

tert-butyl alcohol

[75-65-0]

22630.htm

20-(1-3-0)-(2)-(2)=12

20-(1-×-0)-(1)-(1)=17

BHT3

[128-37-0]

96012.htm

20-(2-1-0)-(4)-(2)=11

20-(2-×-0)-(4)-(2)=11

carbon tetrachloride

[56-23-5]

90116.htm

20-(3-0-0)-(9)-(6)=2

chlorobenzene

[108-90-7]

04730.htm

20-(2-3-0)-(4)-(3)=8

chloroform

[67-66-3]

04770.htm

20-(2-0-0)-(6)-(2)=10

cyclohexane

[110-82-7]

05870.htm

20-(1-3-0)-(6)-(7)=3

20-(1-×-0)-(5)-(5)=9

1,2-dichloroethane

[107-06-2]

09390.htm

20-(2-3-0)-(6)-(2)=7

20-(2-×-0)-(5)-(2)=11

dichloromethane

[75-09-2]

89820.htm

20-(2-1-0)-(1)-(5)=11

20-(2-×-0)-(1)-(5)=10

diethyl ether

[60-29-7]

90868.htm

20-(1-4-1)-(5)-(4)=5

20-(1-×-1)-(4)-(2)=12

diglyme

[111-96-6]

07320.htm

20-(1-2-1)-(4)-(2)=10

20-(1-×-1)-(3)-(2)=13

1,2-dimethoxyethane

[110-71-4]

09450.htm

20-(2-3-0)-(5)-(5)=5

20-(2-×-0)-(4)-(3)=11

N,N-dimethylacetamide

[127-19-5]

07680.htm

20-(2-2-0)-(3)-(2)=11

20-(2-×-0)-(3)-(2)=13

dimethylformamide

[68-12-2]

07860.htm

20-(2-2-0)-(4)-(2)=10

20-(2-×-0)-(4)-(2)=12

dimethylsulfoxide

[67-68-5]

07770.htm

20-(2-2-0)-(0)-(2)=14

20-(2-×-0)-(0)-(2)=16

1,4-dioxane

[123-91-1]

26970.htm

20-(2-3-1)-(6)-(5)=3

20-(2-×-1)-(5)-(4)=8

ethanol

[64-17-5]

89308.htm

20-(2-3-0)-(1)-(4)=10

20-(2-×-0)-(0)-(2)=16

ethyl acetate

[141-78-6]

08750.htm

20-(1-3-0)-(4)-(3)=9

20-(1-×-0)-(3)-(1)=15

ethyl methyl ketone

[78-93-3]

14460.htm

20-(1-3-0)-(4)-(2)=10

20-(1-×-0)-(3)-(1)=15

ethylene diamine

[107-15-3]

96094.htm

20-(3-3-0)-(6)-(6)=2

20-(3-×-0)-(5)-(6)=6

ethylene glycol

[107-21-1]

95630.htm

20-(1-1-0)-(1)-(1)=16

20-(1-×-0)-(1)-(1)=17

formaldehyde

[50-00-0]

96726.htm

20-(3-2-0)-(7)-(9)= -1

20-(3-×-0)-(6)-(7)=4

heptane

[142-82-5]

10680.htm

20-(1-3-0)-(6)-(7)=3

20-(1-×-0)-(5)-(5)=9

n-hexane

[110-54-3]

00235.htm

20-(1-3-0)-(9)-(8)= -1

20-(1-×-0)-(8)-(6)=5

hexanes

[110-54-3]

98123.htm

20-(1-3-0)-(3)-(6)=7

20-(1-×-0)-(2)-(5)=12

HMPA 4

[680-31-9]

22774.htm

20-(2-1-0)-(2)-(2)=13

20-(2-×-0)-(2)-(2)=14

methanol

[67-56-1]

14280.htm

20-(1-3-0)-(8)-(5)=3

20-(1-×-0)-(7)-(4)=8

methyl isobutyl ketone

[108-10-1]

14550.htm

20-(2-3-0)-(5)-(3)=7

20-(2-×-0)-(4)-(2)=12

nitromethane

[75-52-5]

16690.htm

20-(1-3-4)-(3)-(1)=8

20-(1-×-4)-(2)-(1)=12

n-pentane

[109-66-0]

18210.htm

20-(1-4-0)-(6)-(5)=4

20-(1-×-0)-(5)-(3)=11

petroleum ether

[68476-50-6]

18330.htm

20-(1-3-0)-(9)-(6)=1

20-(1-×-0)-(8)-(4)=7

2-propanol

[67-63-0]

12090.htm

20-(1-3-0)-(3)-(5)=8

20-(1-×-0)-(2)-(4)=13

pyridine

[110-86-1]

19990.htm

20-(3-3-0)-(4)-(2)=8

20-(3-×-0)-(3)-(2)=12

tetrahydrofuran

[109-99-9]

23011.htm

20-(2-3-1)-(4)-(3)=7

20-(2-×-1)-(3)-(1)=13

toluene

[108-88-3]

23590.htm

20-(2-3-0)-(7)-(4)=4

20-(2-×-0)-(6)-(4)=8

triethylamine

[121-44-8]

23990.htm

20-(3-3-0)-(5)-(8)=1

20-(3-×-0)-(4)-(7)=7

xylenes

[1330-20-7]

25150.htm

20-(2-3-0)-(5)-(1)=9

20-(2-×-0)-(4)-(1)=13

20-(2-×-0)-(4)-(2)=12

20-(2-×-0)-(3)-(3)=12

2,6-Dimethyl-4-tert-butylphenol hexamethylphosphoramide

5


Standard and solid-supported oxidation procedures: Oxidation of borneol with sodium dichromate5 Procedure Dissolve 2.0g of sodium dichromate dihydrate in 8 mL of water, and carefully add 1.6 mL of concentrated sulfuric acid with an eyedropper. Place the oxidizing solution in an ice bath. While this solution is cooling, dissolve 1.0g of racemic borneol in 4 mL of ether in a 25-mL Erlenmeyer flask and cool it in an ice bath. Remove 6 mL of the sodium dichromate oxidizing mixture you have prepared, and slowly add it with an eyedropper to the cold ether solution over 10 minutes. Swirl the reaction mixture in the ice bath between additions and continue swirling for an additional 5 minutes following the final addition of oxidation. Pour the mixture into a separatory funnel and rinse the Erlenmeyer flask, first with a 10-mL portion of ether and then with 10 mL of water. Add both the rinsings to the separatory funnel. Complete the removal of the aqueous phase and pour the ether layer into a storage vessel. Return the aqueous layer to the separatory funnel and extract it with two successive 10-mL portions of ether. Each time add the ether phase to the storage vessel and return the aqueous layer to the separatory funnel. Return the combined either extracts to the separatory funnel and extract them with 10 mL of 5% sodium bicarbonate. A small amount of solid material may be produced at the interface. Carefully remove the lower aqueous layer and as much of this solid as possible without losing the ether layer. Finally, wash the ether layer with 10 mL of water and drain the lower aqueous layer. The ether layer contains the desired camphor. Pour it out of the top of the separatory funnel, decanting it away from any solids. Dry the ether layer thoroughly with a small amount (about 1g) of anhydrous magnesium sulfate in a stoppered Erlenmeyer flask. Swirl the flask gently until the ether phase is clear. Decant the dry ether phase into a beaker and evaporate the solvent in the hood on a steam bath (using a boiling stone) or with a stream of dry air. When the ether has evaporated and a solid has appeared, remove the flask from the heat source immediately, otherwise the product may sublime prematurely and be lost. Weigh the product. At least 0.4g of crude camphor should be obtained. Purify the material by vacuum (aspirator) sublimation.

Estimated Lab Time - Approximately 2.5 hours Materials Item

CAS #

borneol

[464-45-9]

Hazards

Quantity/Student

Flammable; eye, skin and respiratory irritant

1.0g

Extreme Health Risks; eye, skin and respiratory irritant. Fatal if inhaled or swallowed. Extreme Health Risks; Eye, skin and respiratory irritant. Fatal if inhaled or swallowed. Highly flammable; eye, skin and respiratory irritant

sodium dichromate

[7789-12-0]

sulfuric acid (concd.)

[7664-93-9]

diethyl ether

[60-29-7]

5% sodium bicarbonate

[144-55-8]

10mL

magnesium sulfate

[7487-88-9]

1.0g

20mL dram vial

2.0g 1.6mL 34mL

1

Waste Collection and Disposal Chemical waste generators must determine whether a discarded chemical is classified as a hazardous waste. US EPA guidelines for the classification determination are listed in 40 CFR Parts 261.3. Additionally, waste generators must consult state and local hazardous waste regulations to ensure complete and accurate classification. The following guidelines may be of assistance.

Waste

Hazard Class

borneol, sodium dichromate, sulfuric acid, sodium bicarbonate, water

~5L

corrosive, strong oxidant chromium

diethyl ether

~3L

flammable

magnesium sulfate powder traces of diethyl ether and camphor

5

Quantity Generated / 100 students

~ 100 g

basic, flammable

Notes The aqueous reaction phase and subsequent aqueous washes contain chromium and should be labeled and a strong oxidant and corrosive. Addition of the sodium bicarbonate washes to the aqueous reaction phase in the waste jar will generate heat and CO2 gas, therefore, the cap should be loosely tightened during the combination of aqueous wastes. Be sure to keep the flammable waste container tightly closed. Reacted magnesium sulfate should be collected in a wide-mouth jar.

Pavia, D. L.; Lampman, G. M.; Kriz, G. S. Introduction to Organic Laboratory Techniques; Saunders Golden Sunburst Series; Saunders College Publishing: Fort Worth, TX, 1990.

6


Experiment Tips and Safety Concerns With the hazards and risks associated with sodium dichromate, we do not recommend students to perform this procedure. The information is provided for comparison purposes only. Rubric Evaluation sodium dichromate Oxidant / Reactants Solvent Reaction Isolation Purification Energy Reaction Isolation Purification Purification Method

Details sodium dichromate (20-19), sulfuric acid (20-9), water diethyl ether (20-15) diethyl ether (20-15), sodium bicarbonate, magnesium sulfate none ice room temperature water purification if a water aspirator is used and heat sublimation Total Score

Score 1/20 5/20 5/20 20/20 5/5 5/5 3/5 5/5 49/100

Green Metric Evaluation A balanced equation for the reaction: CH3 CH3

CH3 CH3

CH3 CH3

H + CrO4-2 + H3O+

H

+ H3O+ + CrO3H

O H

H OH

CH3

O CrO3H

CH3

O

CH3

Calculation of Atom Economy: Atom economy considers the amount of starting materials incorporated into the desired final product # MW & # & MW camphor products % ( )100 = % (( % % " MW ( $ MW borneol + MW NaCr2O7 ' reagents ' $ # & 152.23 % ( )100 = 33.6% $154.25 + 298.02 '

Calculation of Effective Mass Yield: Effective mass yield accounts for the relative toxicity as well as the reaction ! efficiency by focusing only on the hazardous components of the waste. It uses the actual masses of reagents used and products generated in the reaction. NOTE: Calculate effective mass yield assuming 100% yield (0.986 g) # & # & Masscamphor % Massproduct ( (( % Mass ( )100 = %% Mass %" Na 2Cr2O7 + MassC 4 H10O + Mass H 2 SO 4 ' nonbenign ( $ material ' $ # & 0.986 % ( )100 = 3.8% $ 2.0 + 2.94 + 21.0 '

Calculation of E-Factor: E-Factor is defined as the g of byproduct divided by the grams of product. The E-Factor provides a chemist with a measure of how many grams of waste is produced for every gram of product. ! Item

Product in grams

camphor

0.986g

Byproduct in grams

sodium dichromate

2.00g

sulfuric acid (concd.) diethyl ether

2.94g 21.0g

sodium bicarbonate anhyd. magnesium sulfate

0.500g 1.00g

water

38.0g

Total

0.986g

65.4 g

E-Factor

65.4 / 0.986 = 66.3

7


Summary: Reagents

https://fscimage. fishersci.com/ msds/

CAS #

(grams) nonbenign

GIV-F

% atom economy

% effective mass yield

E-Factor

33

3.8

66.3

sodium dichromate sodium dichromate

[7789-12-0]

21195.htm

20-(3-0-0)-(12)-(4)=1

2.0


[7664-93-9]

22350.htm

20-(3-0-2)-(1)-(3)=11

2.94

diethyl ether

[60-29-7]

90868.htm

20-(1-X-1)-(4)-(2)=12

21

sodium bicarbonate

[144-55-8]

20970.htm

20-(2-0-0)-(0)-(2)=16

-

magnesium sulfate

[7487-88-9]

13525.htm

20-(1-0-0)-(0)-(2)=17

-

Economic Evaluation Cost

Cost / g or mL

Cost / student

1.00g

$156.00/500g

$0.312/g

$0.312

[7789-12-0]

2.00g

$101.00/500g

$0.202/g

$0.404


[7664-93-9]

1.6mL

$28.30/500mL

$0.057/mL

$0.091

diethyl ether

[60-29-7]

34.0mL

$41.9/L

$0.042/mL

$1.42

sodium bicarbonate

[144-55-8]

0.50g

$17.10/500g

$0.0342/g

$0.017

anhyd. magnesium sulfate

[7487-88-9]

1.0g

$53.20/500g

$0.1064/g

$0.11

water

[7732-18-5]

38mL

-

-

-

Item

CAS #

Quantity

borneol

[464-45-9]

sodium dichromate

Total cost to perform the experiment Total Cost to perform the experiment per gram borneol oxidized

$2.35 $2.35 / 1g = $2.35

Quantity / student

Cost of Disposal


[464-45-9], [7789-12-0], [7664-93-9], [144-55-8], [7732-18-5]

50 mL

X/5L

TBA

diethyl ether

flammable

[60-29-7]

30 mL

X /5L

TBA

magnesium sulfate powder traces of diethyl ether and camphor

basic, flammable

[7487-88-9]

1.0 g

X / 500g

TBA

Item

Hazard Class

CAS #’s


Cost / g or mL

Cost / student

Total cost to dispose of the waste produced in the experiment Total cost to dispose of the waste produced in the experiment per gram borneol oxidized

Final Economic Analysis Educational Experience A. Cost of laboratory experience (per student) (cost to perform / student) + (cost to dispose / student) = $2.35 + $X.XX = B. Total cost of waste based on choice of pathway (per student) (initial cost purchasing “waste-to-be”) + (cost to dispose / student) = ($0.312+$0.404+$0.091+$1.42+$0.017+$0.11= $2.038) + $X.XX = “Industrial Scale” To calculate the cost per gram scale (to normalize microscale and normal scale reactions): A. Cost of oxidizing 1 gram of material through this procedure (cost to perform / gram oxidized) + (cost to dispose / gram oxidized) = $2.35 + $X.XX = B. Total cost of waste to oxidize 1 gram of borneol through this procedure (initial cost purchasing “waste-to-be” / gram oxidized) + (cost to dispose / gram oxidized) = ($2.35 - $0.312 = $2.038) + $X = C. Economic Efficiency of this pathway per gram of oxidized material: (total cost of waste to oxidize 1 gram of borneol / cost of 1 gram borneol) ( $X.XX / $0.312 )

8


Oxidation of borneol with sodium hypochlorite6 Procedure To a 5-mL conical vial add 0.180g of racemic borneol, 0.50 mL of acetone, and 0.15 mL of glacial acetic acid. After adding a spin vane to the vial, attach an air condenser and place the conical vial in a water bath at about 45 ˚C. It is important that the temperature of the water bath remain between 40-50˚C during the entire reaction period. Stir the mixture until the borneol is dissolved. While continuing to stir the reaction mixture, add drop wise 2.0 mL of a bleach solution (5.25% sodium hypochlorite) through the top of the air condenser over a period of about 30 minutes. When the addition is complete, stop stirring the mixture and remove a few drops of the bottom aqueous layer with a Pasteur pipette. Transfer this liquid onto a wet piece of starch-iodide indicator paper to determine if a sufficient amount of bleach has been added. A blue-black color due to the formation of the starch-iodine complex indicates that an excess of hypochlorite is present. If there is no color change, add an additional 0.2 mL of bleach to the reaction mixture, stir for several minutes, and repeat the starch-iodide test. Continue this process until the paper turns blue. Stir the mixture for 10 minutes after the last addition of bleach and repeat the starch-iodide test. If it is negative (absence of blue-black color), add an additional 0.2 mL of bleach. Whether additional bleach was added or not, allow the reaction to continue for 10 minutes more. When the reaction time is complete, allow the mixture to cool to room temperature. Remove the air condenser and add 1.0 mL of CH2Cl2 to extract the camphor. Cap the vial and shake well with venting. Remove the spin vane with forceps and rinse the spin vane and forceps with a few drops of CH2Cl2. Using a filter tip pipette, transfer the lower CH2Cl2 layer into another 5-mL conical vial. Extract the aqueous layer with a second 1.0-mL portion of CH2Cl2 layers with 1.0 mL of saturated sodium bicarbonate solution. Stir the liquid with a stirring rod or spatula until bubbling produced by the formation of carbon dioxide ceases. Cap the vial and shake with frequent venting to release any pressure produced. Transfer the lower CH2Cl2 layer to another container and remove the aqueous layer. Return the CH2Cl2 layer to the vial and wash this solution successively with 1.0 mL of saturated sodium bisulfite and 1.0 mL of water. Using a dry filter tip pipette, transfer the CH2Cl2 to a dry test tube or conical vial. Add three to four microspatula-fulls of granular anhydrous sodium sulfate and let dry for 10-15 minutes with occasional shaking. After tareing a 10-mL Erlenmeyer flask, transfer the CH2Cl2 solution to the flask. Evaporate the solvent in the hood with a gentle stream of dry air or nitrogen gas while heating the Erlenmeyer flask in a sand bath at 40-50 ˚C. As an alternative, leave the flask in the hood until the CH2Cl2 has evaporated. When all the liquid has evaporated and a solid has appeared weigh the flask to determine the weight of your crude product and calculate the percentage yield. Purify all material by vacuum (aspirator) sublimation. Determine the melting point in a sealed capillary tube to prevent sublimation.

Estimated Lab Time - Approximately 2.5 hours Materials Item

CAS #

Hazards

Quantity/Student

borneol

[464-45-9]

Flammable; eye, skin and respiratory irritant

0.180g

acetone

[67-64-1]

Highly flammable; minor eye, skin and respiratory irritant

0.50mL

glacial acetic acid

[64-19-7]

sodium hypochlorite

[7681-52-9]

Causes severe eye, skin, digestive and respiratory tract burns. Flammable. May cause skin, eye, digestive, or respiratory burns

dichloromethane

[75-09-2]

Eye, skin and respiratory irritant

sodium bicarbonate

[144-55-8]

sodium bisulfite

[10034-88-5]

sodium sulfate (anhyd.)

[7757-82-6]

0.15mL 2.4mL 2mL 1.0mL

Eye, skin and respiratory irritant

1.0mL 0.50g

5-mL conical vial

3

air condenser

1

starch-iodide indicator paper

3


6

Pavia, D. L.; Lampman, G. M.; Kriz, G. S.; Engel, R. G. Introduction to Organic Laboratory Techniques, a Small Scale Approach; Third Edition; Saunders College Publishing: Fort Worth, TX, 1999.

9

Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory Quantity Generated / 100 Students

Item

Hazard Class

borneol, acetone, glacial acetic acid, sodium hypochlorite, sodium bicarbonate, sodium bisulfite

1L

corrosive, strong oxidant, flammable

dichloromethane

300 mL

halogenated organic

sodium sulfate, camphor

120 g

basic

Notes The aqueous reaction phase and subsequent aqueous washes contain various chlorine species and a strong acid (and traces of mercury if commercial bleach is used) and should be labeled as an oxidant and corrosive. Addition of the sodium bicarbonate washes to the aqueous reaction phase in the waste jar will generate heat and CO2 gas, therefore, the cap should be loosely tightened during the combination of aqueous wastes. Ideally, all dichloromethane should be collected and disposed of in a waste container labeled halogenated organic solvent waste. Reacted sodium sulfate and camphor should be collected in a widemouth jar.

Experiment Tips and Safety Concerns If this experiment is performed we recommend that mercury free bleach be used. Mercury-free commercial sources of bleach: (a) Spectrowax Elite Bleach, Spectrowax Corp., 155 N Beacon St., Brighton MA, 02135-2049, 617-2542800, 6, 1-gallon bottles $8.50. (b) Valtech Bleach, Fisher Scientific, SR5900, 15L/$73.05. Rubric Evaluation Sodium hypochlorite Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details sodium hypochlorite (20-7), glacial acetic acid (20-10), water acetone (20-11) CH2Cl2 (20-9), sodium bicarbonate (20-2), sodium bisulfite (20-9), anhydrous sodium sulfate (20-4) none 40-50˚C - hot water bath room temperature water purification if water aspirator is used and heat sublimation Total Score

Score 10/20 9/20 11/20 20/20 3/5 5/5 3/5 5/5 66/100


CH3 CH3

CH3 CH3

H +

+ NaClO + H3O

H

+ H3O+ + Cl

O H

H OH

CH3

O

CH3

O

CH3

Cl

Calculation of Atom Economy: Atom economy considers the amount of starting materials incorporated into the desired final product. # MW & # & MW camphor products % ( )100 = % ( % " MW ( $ MW borneol + MW NaOCl ' reagents ' $ # & 152.23 % ( )100 = 66.5% $154.25 + 74.44 '

!

Calculation of Effective Mass Yield: Effective mass yield accounts for the relative toxicity as well as the reaction efficiency by focusing only on the hazardous components of the waste. It uses the actual masses of reagents used and products generated in the reaction. NOTE: Calculate effective mass yield assuming 100% yield (0.178 g)

10


# & # & Masscamphor % Massproduct ( (( % Mass ( )100 = %% Mass %" NaOCl + MassCH 3COOH + MassCH 2Cl 2 ' $ nonbenign ( material ' $ # & 0.178 % ( )100 = 3.1% $ 2.8 + 0.158 + 2.65 '

!

Calculation of E-Factor: E-Factor is defined as the g of byproduct divided by the grams of product. The E-Factor provides a chemist with a measure of how many grams of waste is produced for every gram of product. Item

Product in grams

camphor

0.178

Byproduct in grams

acetone glacial acetic acid

0.396 0.158

sodium hypochlorite

2.80

dichloromethane sat. sodium bicarbonate

2.65 0.164

sat. sodium bisulfite

1.00

water sodium sulfate anhydrous

3.00 0.500

Total

0.178

10.7

E-Factor

10.7 / 0.178 = 60.1

Summary

CAS #


GIV-F

(grams) if non-benign

[67-64-1] [64-19-7]

00140.htm 00120.htm

20-(1-X-0)-(3)-(2)=14 20-(3-2-0)-(2)-(3)=10

0.158

sodium hypochlorite

[7681-52-9]

40179.htm

20-(0-0-0)-(2)-(3)=15

2.8

commercial bleach with mercury

[7681-52-9] [7439-97-6]

96252.htm

20-(0-0-0)-(2)-(3)=15 15-(3-0-0)-(2)-(2)=8

2.8

dichloromethane

[75-09-2]

89820.htm

20-(2-1-0)-(1)-(5)=11

2.65

sodium bicarbonate sodium bisulfite

[144-55-8] [10034-88-5]

20970.htm 20995.htm

20-(2-0-0)-(0)-(2)=16 20-(3-0-0)-(1)-(2)=14

-

sodium sulfate anhydrous

[7757-82-6]

21630.htm

20-(1-0-1)-(0)-(2)=16

-

Reagents sodium hypochlorite acetone glacial acetic acid

% atom economy 66.5

% effective mass yield 3.1

E-Factor 60.1

Economic Evaluation Item

CAS #

Quantity

Cost

Cost / g or mL

Cost / student

borneol

[464-45-9]

0.180g

$156.00/500g

$0.312/g

$0.0562

acetone

[67-64-1]

0.500mL

$25.30/L

$0.0253/mL

$0.0127

glacial acetic acid

[64-19-7]

0.150mL

$27.20/500mL

$0.054/mL

$0.00816

sodium hypochlorite

[7681-52-9]

2.40mL

$32.30/500mL

$0.0646/mL

$0.155

dichloromethane

[75-09-2]

2.0mL

$24.20/500mL

$0.0484/mL

$0.0968

sodium bicarbonate

[144-55-8]

0.164g

$17.10/500g

$0.0342/g

$0.00561

sodium bisulfite

[10034-88-5]

1.0g

$16.70/500g

$0.0334/g

$0.033


[7757-82-6]

0.50g

$30.20/500g

$0.0604/g

$0.030

Water

[7732-18-5]

3mL

-

-


$0.397 $0.397 / 0.180 g =$2.21

11


Quantity / student

Cost of Disposal

[464-45-9], [67-64-1], [64-19-7], [7681-52-9], [144-55-8], [10034-88-5]

10 mL

X/5 Liters

TBA

[75-09-2]

3 mL

X /5 Liters

TBA

[7757-82-6]

1g

X / 500g

Item

Hazard Class

CAS #’s

borneol, acetone, glacial acetic acid, sodium hypochlorite, sodium bicarbonate, sodium bisulfite


dichloromethane

halogenated organic

sodium sulfate anhydrous, camphor

basic

Cost / g or mL

Cost / student

TBA

Total cost to dispose of the waste produced in the experiment Total cost to dispose of the waste produced in the experiment per gram borneol oxidized Quantity / student

Cost of Disposal

[464-45-9], [67-64-1], [64-19-7], [7681-52-9], [144-55-8], [10034-88-5]

10 mL

X/5 Liters

TBA

[75-09-2]

3 mL

X /5 Liters

TBA

[7757-82-6]

1g

X / 500g

TBA

Item

Hazard Class

CAS #’s

borneol, acetone, glacial acetic acid, sodium hypochlorite, sodium bicarbonate, sodium bisulfite, with traces of mercury

corrosive, strong oxidant, flammable, mercury

dichloromethane

halogenated organic


basic

Cost / g or mL

Cost / student


Final Economic Analysis Educational Experience A. Cost of laboratory experience (per student) (cost to perform / student) + (cost to dispose / student) = $0.397 + $X.XX = B. Total cost of waste based on choice of pathway (per student) (initial cost purchasing “waste-to-be”) + (cost to dispose / student) = ($0.0127+$0.00816+$0.155+$0.0968+$0.00561+$0.033+$0.030 = $0.341) + $X.XX = “Industrial Scale” To calculate the cost per gram scale (to normalize microscale and normal scale reactions): A. Cost of oxidizing 1 gram of material through this procedure (cost to perform / gram oxidized) + (cost to dispose / gram oxidized) = $2.21 + $X.XX = B. Total cost of waste to oxidize 1 gram of borneol through this procedure (initial cost purchasing “waste-to-be” / gram oxidized) + (cost to dispose / gram oxidized) = ($2.21 - $0.312 = $1.90) + $X. C. Economic Efficiency of this pathway per gram of oxidized material: (total cost of waste to oxidize 1 gram of borneol / cost of 1 gram borneol) ( $X.XX / $0.312 )

12


Oxidation of Borneol with active Manganese Dioxide on Silica – Year #1 Start

7

Procedure

Add “active” MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.154 g, 1 mmol) to a pestle. Grind with the mortar until a homogenous mixture of borneol in AMD-silica is obtained, generally 5 to 7 minutes. Transfer this sample via weighing paper into a glass scintillation vial. Cap the vessel and place in the center of a microwave. Microwave on high power for 5 intervals of 20 seconds each, turning the microwave off for 20 seconds in between each interval. Carefully, remove the hot vial. Once the glass is cool, stir the solid in the vial and transfer a small spatula full to a second vial and add 10 drops of diethyl ether. Mix thoroughly and let the solids settle to the bottom. Spot a TLC plate with a) 2% of borneol in diethyl ether, b) 2% of camphor in diethyl ether, and c) your diethyl ether extract. Develop the TLC plate using CH2Cl2 / CH3OH (2:1) as the developing solvent. Use an iodine chamber to observe the spots on the TLC plate. If borneol is still present in your reaction mixture, grind your reaction mixture again in the mortar with the pestle and begin the microwave heating process again. Once the reaction appears to be complete add 5 mL of CH2Cl2 to the reaction mixture and mix thoroughly to extract the camphor product. Separate the organic layer by vacuum filtration. Dry the CH2Cl2 solution over a small amount of anhydrous sodium sulfate and re-filter to remove the solid. Remove the solvent by rotary evaporation to obtain crude product. Redissolve crude product in a minimum amount of diethyl ether to transfer to a sublimation chamber. Purify the material by vacuum (aspirator) sublimation. Transfer your product to a sealed vial and measure the IR spectrum of your product.

Estimated Lab Time - Approximately 1 hour Materials CAS #

borneol (1mmol)

[464-45-9]

active MnO2 (4mmol)

[1313-13-9]

0.348g

silica gel (230-400 mesh with large surface area of 600m2/g)

[112926-00-8]

0.652g

diethyl ether

[60-29-7]

dichloromethane

[75-09-2]

methanol

[67-56-1]


[7757-82-6]

Hazards Flammable, eye, skin and respiratory irritant

Quantity/ Student

Item

Highly flammable, eye, skin and respiratory irritant Eye, skin and respiratory irritant Highly flammable, eye, skin and respiratory irritant

0.154g

20mL 35mL 10mL 0.25g

mortar with pestle

1

glass scintillation vial

2

sublimation chamber

1

standard silica TLC plates

2 or 3


Item borneol, manganese dioxide, silica gel, sodium sulfate, TLC plates diethyl ether, dichloromethane

7

Quantity Generated / 100 Students ~150g

7.5 L

Hazard Class

Notes


Reacted AMD-silica and the used TLC plates can be collected in a wide mouth jar.

halogenated organic

Ideally, all dichloromethane, methanol and ether should be collected and disposed of in a waste container labeled halogenated organic solvent waste.

Varma, R. S.; Saini, R. K.; Dahiya, R. Tetrahedron Letters, 1997, 38, 7823 - 7824

13


Experiment Tips and Safety Concerns A standard household microwave can be used safely for this procedure. Operation of the microwave in a fume hood is recommended. Microwave irradiation can be inhomogeneous. Care must be taken so that the microwave does not overheat; beakers of alumina, sand, silica gel, or dry ice have been used successfully to absorb excess microwave energy. A beaker of water is not recommended as it interferes with the characterization of the product. Rubric Evaluation Active Manganese Dioxide on Silica Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details

Score

active manganese dioxide (20-6), silica (20-0) none CH2Cl2 (20-9), anhydrous sodium sulfate (20-4) diethyl ether (20-15) microwave room temperature water purification if water aspirator is used and heat sublimation

14/20 20/20 11/20 5/20 5/5 5/5 3/5 5/5 68/100

Total Score


CH3 CH3

CH3 CH3

+ MnO2 + silica gel + HSiO2+ + MnOH

SiO2 H

H OH

CH3

O MnOH

CH3 O

CH3

Calculation of Atom Economy: Atom economy considers the amount of starting materials incorporated into the desired final product. # MW & # & MW camphor products % ( )100 = % (( % % " MW ( $ MW borneol + MW MnO2 ' reagents ' $ # & 152.23 % ( )100 = 63.1% $154.25 + 86.94 '

!

Calculation of Effective Mass Yield: Effective mass yield accounts for the relative toxicity as well as the reaction efficiency by focusing only on the hazardous components of the waste. It uses the actual masses of reagents used and products generated in the reaction. Calculate effective mass yield assuming 100% yield (0.152 g). # & # Mass & % Massproduct ( camphor (( % Mass ( )100 = %% Mass %" CH 2Cl 2 ' $ nonbenign ( material ' $ # 0.152 & % ( )100 = 2.3% $ 6.63 '

!

Diethyl ether was not considered in this calculation because it was only used to test the progress of the reaction. It could have also been used in the other procedures and it was not, therefore, it was not counted here.

14



Product in grams

camphor

0.152g

Byproduct in grams

active MnO2

0.348

silica gel dichloromethane

0.652 6.625

anhydrous sodium sulfate

E-Factor

0.25

Total

0.152

7.875

51.8

Summary:

Reagents CAS # active manganese dioxide – Year #1 Start


GIV-F


active MnO2

[1313-13-9]

13610.htm

20-(0-0-0)-(2)-(1)=17

-

silica gel

[112926-00-8]

20665.htm

20-(0-0-0)-(0)-(0)=20

-

diethyl ether

[60-29-7]

90868.htm

20-(1-X-1)-(4)-(2)=12

0.28

dichloromethane

[75-09-2]

89820.htm

20-(2-1-0)-(1)-(5)=11

6.625

% atom economy 63.1


E-Factor 51.8


CAS #

Quantity

Cost

Cost / g or mL

Cost / student

borneol (1mmol)

[464-45-9]

0.154g

$156.00/500g

$0.312/g

$0.048

active MnO2 (4mmol)

[1313-13-9]

0.348g

$165.50/500g

$0.331/g

$0.115


[112926-00-8]

0.652g

$47.70/100g

$0.477/g

$0.311

diethyl ether

[60-29-7]

20mL

$41.9/L

$0.0419/mL

$0.838

dichloromethane

[75-09-2]

35mL

$24.20/500mL

$0.0484/mL

$1.69

methanol

[67-56-1]

10mL

$18.70/500mL

$0.0374/mL

$0.374


[7757-82-6]

0.25g

$30.20/500g

$0.0604/g

$0.0151

Total cost to perform the experiment Total Cost to perform the experiment per gram borneol oxidized Quantity / student

Cost of Disposal

[464-45-9], [1313-13-9], [112926-00-8]

1.2 g

X / 500g

TBA

halogenated organic

[60-29-7], [75-09-2], [67-56-1]

75 mL

X /5 Liters

TBA

basic

[7757-82-6]

0.25g

X / 500g

TBA

Item

Hazard Class

CAS #’s

borneol, manganese dioxide, silica gel


diethyl ether, dichloromethane sodium sulfate anhydrous

Cost / g or mL

$3.39 $22.01

Cost / student


15


Final Economic Analysis Educational Experience A. Cost of laboratory experience (per student) (cost to perform / student) + (cost to dispose / student) = $3.39 + $X.XX = B. Total cost of waste based on choice of pathway (per student) (initial cost purchasing “waste-to-be”) + (cost to dispose / student) = ($0.115 + $0.311 + $0.838 + $1.69 + $0.374 + $0.0151 = $3.342) + $X.XX = “Industrial Scale” To calculate the cost per gram scale (to normalize microscale and normal scale reactions): A. Cost of oxidizing 1 gram of material through this procedure (cost to perform / gram oxidized) + (cost to dispose / gram oxidized) = $22.01 + $X.XX = B. Total cost of waste to oxidize 1 gram of borneol through this procedure (initial cost purchasing “waste-to-be” / gram oxidized) + (cost to dispose / gram oxidized) = ($22.01- $0.312 = $21.70) + $X. C. Economic Efficiency of this pathway per gram of oxidized material: (total cost of waste to oxidize 1 gram of borneol / cost of 1 gram borneol) ( $X.XX / $0.312 )

16


Oxidation of Borneol with active Manganese Dioxide on Silica – Final ‘Greenest’ Method

8

Procedure

Mix 'active' MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.31 g, 2 mmol) with a spatula for 5 minutes in a small beaker. Transfer this sample into a pile in the center of a large watch glass. Place an inverted glass powder funnel on top with a small watch glass covering the end and place on top of the warm hot plate. Best temperature “program”: 25oC to 165oC over ~5 min.; hold at 165oC for 10 min.; ramp up to 200oC over 5 min. and hold at 200oC for 10 min.). Weigh the funnel and the small watch glass separately. The combined result is your yield. Run TLC/IR/NMR/GC on your product to check the purity. The melting point of the product can be determined by a sealed capillary tube melting point determination

Estimated Lab Time - Approximately 1 hour Materials CAS #

borneol (2 mmol)

[464-45-9]

active MnO2 (4mmol)

[1313-13-9]

0.348g


[112926-00-8]

0.652g

Thick watch glass works better than thin watch glass

1

Watch glass Glass Powder Funnel Small watch glass Vial Plastic Powder funnel

Hazards Flammable, eye, skin and respiratory irritant

Quantity/ Student

Item

1 1 1 1

To collect product Good for putting reagents in a pile To remove glassware from the hotplate.

Tongs Hotplate Thermocouple

0.31g

1 Can cause burns if touched.

To monitor the temperature of hotplate. Ensures better product.

1 1

Waste Collection and Disposal Chemical waste generators must determine whether a discarded chemical is classified as a hazardous waste. US EPA guidelines for the classification determination are listed in 40 CFR Parts 261.3. Additionally, waste generators must consult state and local hazardous waste regulations to ensure complete and accurate classification. The following guidelines may be of assistance. Item borneol, manganese dioxide, silica gel

Quantity Generated / 100 Students 120 g

Hazard Class corrosive, strong oxidant

Notes Reacted AMD-silica, borneol and camphor can be collected in a wide mouth jar.

Experiment Tips and Safety Concerns A standard household microwave can be used safely for this procedure. Operation of the microwave in a fume hood is recommended. Microwave irradiation can be inhomogeneous. Care must be taken so that the microwave does not overheat; beakers of alumina, sand, silica gel, or dry ice have been used successfully to absorb excess microwave energy. A beaker of water is not recommended as it interferes with the characterization of the product. As relatively low yields are obtained from this reaction in the microwave, it is recommended that the reaction take place on a hotplate as described in the procedure. Students can compare the energy saved in using a microwave as compared to the hotplate and then consider whether the savings justifies the low yields they obtain in the microwave.

8

Varma, R. S.; Saini, R. K.; Dahiya, R. Tetrahedron Letters, 1997, 38, 7823 - 7824.

17


Rubric Evaluation AMD on Silica Final Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details active manganese dioxide (20-6), silica (20-0) none none none hot plate – 15 minutes hot plate – 15 minutes hot plate – 15 minutes sublimation Total Score

Score 14/20 20/20 20/20 20/20 3/5 3/5 3/5 5/5 87/100


CH3 CH3

CH3 CH3


SiO2 H

H OH

CH3

O MnOH

CH3 O

CH3

Calculation of Atom Economy: Atom economy considers the amount of starting materials incorporated into the desired final product. # MW & # & MW camphor products % ( )100 = % (( % MW % " MW ( borneol + MW MnO2 ' $ reagents ' $ # & 152.23 % ( )100 = 63.1% $154.25 + 86.9368 '

!

Calculation of Effective Mass Yield: Effective mass yield accounts for the relative toxicity as well as the reaction efficiency by focusing only on the hazardous components of the waste. It uses the actual masses of reagents used and products generated in the reaction. Calculate effective mass yield assuming 100% yield (0.306 g). # & # & % Masscamphor ( % Massproduct ( ( % Mass ( )100 = % Mass %" no*nonbenign ( % nonbenign ( material material ' $ $ ' # 0.306 & % ( )100 = 100% $ 0 '

!


Product in grams

camphor

0.306

active MnO2 silica gel Total

Byproduct in grams

E-Factor

0.348 0.652 0.306

1

3.27

18


Summary

Reagents CAS # active manganese dioxide – Final


GIV-F


active MnO2

[1313-13-9]

13610.htm

20-(0-0-0)-(2)-(1)=17

-

silica gel

[112926-00-8]

20665.htm

20-(0-0-0)-(0)-(0)=20

-

% atom economy 63.1

% effective mass yield 100

E-Factor 3.27


CAS #

Quantity

Cost

Cost / g or mL

Cost / student

borneol (1mmol)

[464-45-9]

0.31g

$156.00/500g

$0.312/g

$0.097

active MnO2 (4mmol)

[1313-13-9]

0.348g

$165.50/500g

$0.331/g

$0.115


[112926-00-8]

0.652g

$47.70/100g

$0.477/g

$0.311


$0.523 $1.69

Amount of initial cost purchasing “waste-to-be”- materials that must be disposed of per gram borneol oxidized: $0.426 / 0.31 = $1.37 Item

Hazard Class

CAS #’s



[464-45-9], [1313-13-9], [112926-00-8]

Quantity / student

Cost of Disposal

1.2 g

X / 500g

Cost / g or mL

Cost / student TBA


Final Economic Analysis Educational Experience A. Cost of laboratory experience (per student) (cost to perform / student) + (cost to dispose / student) = $0.523 + $X.XX = B. Total cost of waste based on choice of pathway (per student) (initial cost purchasing “waste-to-be”) + (cost to dispose / student) = ($0.115 + $0.311 = $0.426) + $X.XX = “Industrial Scale” To calculate the cost per gram scale (to normalize microscale and normal scale reactions): A. Cost of oxidizing 1 gram of material through this procedure (cost to perform / gram oxidized) + (cost to dispose / gram oxidized) = $1.69 + $X.XX = B. Total cost of waste to oxidize 1 gram of borneol through this procedure (initial cost purchasing “waste-to-be” / gram oxidized) + (cost to dispose / gram oxidized) = ($1.69 - $0.312 = $1.38) + $X. C. Economic Efficiency of this pathway per gram of oxidized material: (total cost of waste to oxidize 1 gram of borneol / cost of 1 gram borneol) ( $X.XX / $0.312 )

19


Instructor Solution Manual Greening the Oxidation of Borneol to Camphor 1. A Guided-Inquiry Investigation into Green Metrics What is the toxicity of all of the chemicals used in the synthetic transformation? Which of the 12 Principles of Green Chemistry and associated with the discussion above?___Principles 1 & 3____ Are catalytic or stoichiometric reagents being used? Which of the 12 Principles of Green Chemistry and associated with the discussion above?___Principle 9______ What auxiliary substances, such as solvents, drying agents, etc., are needed? Which of the 12 Principles of Green Chemistry and associated with the discussion above?____ Principle 5_______ Can we minimize the energy required in the transformation? Which of the 12 Principles of Green Chemistry and associated with the discussion above?____ Principle 6______ Reagents ethanol

CAS # [64-17-5]

Green Index Value 20-(2-3-0)-(1)-(4)=10

Reagents ethanol

CAS # [64-17-5]

Green Index Value w/o flammability 20-(2-×-0)-(0)-(2)=16

Evaluating the “Greenness” of a Reaction Reagents sodium dichromate

https://fscimage.fishersci.com/ msds/

green-index-value

CAS #

*considering flammability


sodium dichromate

[7789-12-0]

21195.htm

20-(3-0-0)-(12)-(4)=1

2.0


[7664-93-9]

22350.htm

20-(3-0-2)-(1)-(3)=11

2.94

diethyl ether

[60-29-7]

90868.htm

20-(1-4-1)-(5)-(4)=5* 20-(1-X-1)-(4)-(2)=12

21

sodium bicarbonate

[144-55-8]

20970.htm

20-(2-0-0)-(0)-(2)=16

-

magnesium sulfate

[7487-88-9]

13525.htm

20-(1-0-0)-(0)-(2)=17

-

[67-64-1]

00140.htm

20-(1-3-0)-(4)-(3)=9* 20-(1-X-0)-(3)-(2)=14

-

sodium hypochlorite acetone glacial acetic acid

[64-19-7]

00120.htm

20-(3-2-0)-(2)-(3)=10

0.158

sodium hypochlorite

[7681-52-9]

40179.htm

20-(0-0-0)-(2)-(3)=15

2.8

commercial bleach Hgo

[7681-52-9]

dichloromethane

[75-09-2]

89820.htm

20-(2-1-0)-(1)-(5)=11

2.65

sodium bicarbonate

[144-55-8]

20970.htm

20-(2-0-0)-(0)-(2)=16

-

sodium bisulfite

[10034-88-5]

20995.htm

20-(3-0-0)-(1)-(2)=14

-

sodium sulfate

[7757-82-6]

21630.htm

20-(1-0-1)-(0)-(2)=16

-

[7439-97-6]

96252.htm

20-(0-0-0)-(2)-(3)=15 15-(3-0-0)-(2)-(2)=8

2.8

active manganese dioxide – Year #1 Start active MnO2

[1313-13-9]

13610.htm

20-(0-0-0)-(2)-(1)=17

-

silica gel

[112926-00-8]

20665.htm

20-(0-0-0)-(0)-(0)=20

0.28

diethyl ether

[60-29-7]

90868.htm

20-(1-4-1)-(5)-(4)=5* 20-(1-X-1)-(4)-(2)=12

dichloromethane

[75-09-2]

89820.htm

20-(2-1-0)-(1)-(5)=11

6.625

active MnO2

[1313-13-9]

13610.htm

20-(0-0-0)-(2)-(1)=17

-

silica gel

[112926-00-8]

20665.htm

20-(0-0-0)-(0)-(0)=20

-

active manganese dioxide – Final

20

Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory Sodium hypochlorite Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Active Manganese Dioxide on Silica Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details sodium hypochlorite (20-7), glacial acetic acid (20-10), water acetone (20-11) CH2Cl2 (20-9), sodium bicarbonate (20-2), sodium bisulfite (20-9), anhydrous sodium sulfate (20-4) none 40-50˚C room temperature water purification and heat sublimation Total Score

Score 10/20 9/20 11/20 20/20 3/5 5/5 3/5 5/5 66/100

Details

Score

active manganese dioxide (20-6), silica (20-0) none CH2Cl2 (20-9), anhydrous sodium sulfate (20-4) none microwave none recrystalization sublimation

14/20 20/20 11/20 20/20 5/5 5/5 4/5 5/5 84/100

Total Score

Assessing the efficiency of Oxidation reactions using green metrics 1.Write a balanced equation for each reaction. a) sodium dichromate: CH3 CH3

CH3 CH3

CH3 CH3

H + CrO4-2 + H3O+

H

+ H3O+ + CrO3H

O H

H OH

CH3

O CrO3H

CH3

CH3

O

b) sodium hypochlorite: CH3 CH3

CH3 CH3

CH3 CH3 H +

+ NaClO + H3O

H

+ H3O+ + Cl

O H

H OH

CH3

O

CH3

O

CH3

Cl

c) active manganese dioxide on silica: CH3 CH3

CH3 CH3

CH3 CH3


SiO2 H

H OH

CH3

O MnOH

CH3 O

CH3

21


2. Calculate the atom economy for all three reactions. How do they compare? a) sodium dichromate:

# MW & # & MW camphor products % ( )100 = % (( % % " MW ( $ MW borneol + MW NaCr2O7 ' reagents ' $ # & 152.23 % ( )100 = 33.6% $154.25 + 298.02 '

! b) sodium hypochlorite:

# MW & # & MW camphor products % ( )100 = % ( % " MW ( MW + MW $ borneol NaOCl ' reagents ' $ # & 152.23 % ( )100 = 66.5% $154.25 + 74.44 '

! dioxide on silica: c) active manganese

# MW & # & MW camphor products % ( )100 = % (( % MW % " MW ( borneol + MW MnO2 ' $ reagents ' $ # & 152.23 % ( )100 = 63.1% $154.25 + 86.9368 '

3. Effective mass yield accounts for the relative toxicity as well as the reaction efficiency by focusing ! of the waste. It uses the actual masses of reagents used and products only on the hazardous components generated in the reaction. Calculate the effective mass yield for all the reactions. How do they compare? a) sodium dichromate: NOTE: Calculate effective mass yield assuming 100% yield (0.986 g) # & # & Masscamphor % Massproduct ( (( % Mass ( )100 = %% Mass %" Na 2Cr2O7 + MassC 4 H10O + Mass H 2 SO 4 ' nonbenign ( $ material ' $ # & 0.986 % ( )100 = 3.8% $ 2.0 + 2.94 + 21.0 '

b) sodium hypochlorite: NOTE: Calculate effective mass yield assuming 100% yield (0.178 g) !

# & # & Masscamphor % Massproduct ( (( % Mass ( )100 = %% Mass %" NaOCl + MassCH 3COOH + MassCH 2Cl 2 ' $ nonbenign ( material ' $ # & 0.178 % ( )100 = 3.1% $ 2.8 + 0.158 + 2.65 '

c) active MnO2 on silica (Year #1 Start): NOTE: Calculate effective mass yield assuming 100% yield g)

! (0.152

# & # Mass & % Massproduct ( camphor (( % Mass ( )100 = %% Mass %" CH 2Cl 2 ' $ nonbenign ( material ' $ # 0.152 & % ( )100 = 2.3% $ 6.625 '

!

22


4. Calculation of E-Factor: E-Factor is defined as the g of byproduct divided by the grams of product. The E-Factor provides a chemist with a measure of how many grams of waste is produced for every gram of product.

a) sodium dichromate: Item

Product in grams

camphor

0.986g

Byproduct in grams

sodium dichromate sulfuric acid (concd.)

2.00g 2.94g

diethyl ether sodium bicarbonate

21.0g 0.500g


1.00g

water

E-Factor

38.0g

Total

0.986g

65.4 g

65.4 / 0.986 = 66.3

Item

Product in grams

Byproduct in grams

E-Factor

camphor

0.178

b) sodium hypochlorite acetone glacial acetic acid

0.396

sodium hypochlorite dichloromethane

2.80 2.65

sat. sodium bicarbonate sat. sodium bisulfite

0.164 1.00

0.158

water

3.00


0.500

Total

0.178

10.7

10.7 / 0.178 = 60.1

Item

Product in grams

Byproduct in grams

E-Factor

camphor

0.152g

c) active MnO2 on silica (Year #1 Start): active MnO2

0.348

silica gel dichloromethane

0.652 6.625

anhydrous sodium sulfate

0.25

Total

0.152

7.875

51.8

Economic Evaluation

a) sodium dichromate: Cost

Cost / g or mL

Cost / student

1.00g

$156.00/500g

$0.312/g

$0.312

[7789-12-0]

2.00g

$101.00/500g

$0.202/g

$0.404


[7664-93-9]

1.6mL

$28.30/500mL

$0.057/mL

$0.091

diethyl ether

[60-29-7]

34.0mL

$41.9/L

$0.042/mL

$1.42

sodium bicarbonate

[144-55-8]

0.50g

$17.10/500g

$0.0342/g

$0.017


[7487-88-9]

1.0g

$53.20/500g

$0.1064/g

$0.11

water

[7732-18-5]

38mL

-

-

Item

CAS #

Quantity

borneol

[464-45-9]

sodium dichromate


$2.35 $2.35 / 1g = $2.35

23


b) sodium hypochlorite Item

CAS #

Quantity

Cost

Cost / g or mL

Cost / student

borneol

[464-45-9]

0.180g

$156.00/500g

$0.312/g

$0.0562

acetone

[67-64-1]

0.500mL

$25.30/L

$0.0253/mL

$0.0127

glacial acetic acid

[64-19-7]

0.150mL

$27.20/500mL

$0.054/mL

$0.00816

sodium hypochlorite

[7681-52-9]

2.40mL

$32.30/500mL

$0.0646/mL

$0.155

dichloromethane

[75-09-2]

2.0mL

$24.20/500mL

$0.0484/mL

$0.0968

sodium bicarbonate

[144-55-8]

0.164g

$17.10/500g

$0.0342/g

$0.00561

sodium bisulfite

[10034-88-5]

1.0g

$16.70/500g

$0.0334/g

$0.033


[7757-82-6]

0.50g

$30.20/500g

$0.0604/g

$0.030

Water

[7732-18-5]

3mL

-

-

-


$0.397 $0.397 / 0.180 g =$2.21

c) active MnO2 on silica (Year #1 Start): Item

CAS #

Quantity

Cost

Cost / g or mL

Cost / student

borneol (1mmol)

[464-45-9]

0.154g

$156.00/500g

$0.312/g

$0.048

active MnO2 (4mmol)

[1313-13-9]

0.348g

$165.50/500g

$0.331/g

$0.115


[112926-00-8]

0.652g

$47.70/100g

$0.477/g

$0.311

diethyl ether

[60-29-7]

20mL

$41.9/L

$0.0419/mL

$0.838

dichloromethane

[75-09-2]

35mL

$24.20/500mL

$0.0484/mL

$1.69

methanol

[67-56-1]

10mL

$18.70/500mL

$0.0374/mL

$0.374


[7757-82-6]

0.25g

$30.20/500g

$0.0604/g

$0.0151


$3.39 $22.01

24


Summary

CAS #


*considering flammability


sodium dichromate

[7789-12-0]

21195.htm

20-(3-0-0)-(12)-(4)=1

2.0


[7664-93-9]

22350.htm

20-(3-0-2)-(1)-(3)=11

2.94

diethyl ether

[60-29-7]

90868.htm

20-(1-4-1)-(5)-(4)=5* 20-(1-X-1)-(4)-(2)=12

21

sodium bicarbonate

[144-55-8]

20970.htm

20-(2-0-0)-(0)-(2)=16

-

magnesium sulfate

[7487-88-9]

13525.htm

20-(1-0-0)-(0)-(2)=17

-

Reagents sodium dichromate

Green Index Value

sodium hypochlorite [67-64-1]

00140.htm

20-(1-3-0)-(4)-(3)=9* 20-(1-X-0)-(3)-(2)=14

-

[64-19-7]

00120.htm

20-(3-2-0)-(2)-(3)=10

0.158

sodium hypochlorite

[7681-52-9]

40179.htm

20-(0-0-0)-(2)-(3)=15

2.8


[7681-52-9] [7439-97-6]

96252.htm

20-(0-0-0)-(2)-(3)=15 15-(3-0-0)-(2)-(2)=8

2.8

dichloromethane

[75-09-2]

89820.htm

20-(2-1-0)-(1)-(5)=11

1.3

sodium bicarbonate

[144-55-8]

20970.htm

20-(2-0-0)-(0)-(2)=16

-

sodium bisulfite

[10034-88-5]

20995.htm

20-(3-0-0)-(1)-(2)=14

-


[7757-82-6]

21630.htm

20-(1-0-1)-(0)-(2)=16

-

acetone glacial acetic acid

active manganese dioxide – Year #1 Start active MnO2

[1313-13-9]

13610.htm

20-(0-0-0)-(2)-(1)=17

-

silica gel

[112926-00-8]

20665.htm

20-(0-0-0)-(0)-(0)=20

-

diethyl ether

[60-29-7]

90868.htm

20-(1-4-1)-(5)-(4)=5* 20-(1-X-1)-(4)-(2)=12

0.28

dichloromethane

[75-09-2]

89820.htm

20-(2-1-0)-(1)-(5)=11

6.5

active manganese dioxide – Final active MnO2

[1313-13-9]

13610.htm

20-(0-0-0)-(2)-(1)=17

-

silica gel

[112926-00-8]

20665.htm

20-(0-0-0)-(0)-(0)=20

-

% atom economy 33.6

E-Factor 66.3


66.5

59.9

3.1

63.1

51.8

2.3

63.1

3.27

100

25


Instructor Solution Manual Greening the Oxidation of Borneol to Camphor 2. An Open-Inquiry Experiment Spectroscopic Data: NMR- 1H NMR can be prepared in CDCl3. 5% borneol can be observed in a predominately camphor sample on an Anasazi EFT 90 MHz NMR. Ratios of borneol to camphor in the sample can be quantitatively determined by comparing the intensity of the 1H NMR signal of Ha in borneol (~4.0 ppm) to that of Hb in camphor (~2.3 ppm). Hb in both borneol and camphor resonates at ~2.3 ppm and, therefore, should always integrate as 1 as compared to Ha which is unique to borneol. The 1H NMR spectrum and peak assignments for (1S-endo)-borneol and both (+-)-camphor and (+)-camphor can be found at the Spectral Data Base for Organic Compounds at the following URL: http://www.aist.go.jp/RIODB/SDBS/cgi-bin/cre_index.cgi (accessed June 2007) CH3

CH3

Hb

CH3

CH3

O

CH3

Hb

Hc Ha OH

CH3

Hc

IR- Infrared spectrum of neat product can be collected using sliver halide plates and agrees with literature spectrum for camphor. The most important peaks appear at 2961, 2874, and 1744. Peaks appearing at 2961 and 2874 are the sp3 C-H stretches while the peak at 1744 is the C=O stretch of the ketone functional group. GC - The reaction product ratio can be followed by GC using a standard GowMac GC using temperature settings typically suited for the separation of cyclohexane and toluene.

Procedural Introduction: The procedure given in the student handout corresponds to the “Year #1 (Actual Procedure below). Herein, the questions students raised, as well as the answers they obtained and the new problems they encountered are described. This information is provided to guide instructors in the methods of greening and overall procedure development. The final modified procedure incorporating all of the changes adopted in Year #1 is also provided. The rubric evaluation before and after the Year #1 improvements is also provided for comparison. Two additional iterations for subsequent years is also provided to show the progression of the procedural changes. The final ‘greenest’ procedure after three years of student research can be found below.

Procedures:

(Directly adapted from procedures of Rajender Varma, et al.1: Add “active” MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.154 g, 1 mmol) to a pestle. Grind with the mortar until a homogenous mixture of borneol in AMD-silica is obtained. Transfer this sample into a glass scintillation vial. Cap the vessel and place in the center of a microwave. Microwave at maximal intensity for 100 s. Remove the hot vial carefully. Once the glass is cool, remove the cap and add 5 mL of CH2Cl2. Separate the organic layer by filtering in vacuo (if desired, this layer may be dried and refiltered), and remove the solvent to obtain crude product. Year #1 (Summary) - Grind active MnO2, silica gel, and borneol in a mortar and pestle, until a homogenous mixture is obtained. Transfer this sample into a capped glass scintillation vial. Place in the center of a household microwave. Microwave at maximum intensity for 100 s. Remove the hot vial carefully. Follow the reaction, by TLC (CH2Cl2) of a 1 mL diethyl ether extract of a spatula of the reaction material. Repeat the microwave heating as necessary. Once the reaction is complete by TLC and the reaction material is cooled to room temperature add 5 mL of CH2Cl2. Separate the organic layer by vacuum filtration and remove the solvent to obtain crude product. Redissolve crude product in a minimum amount of diethyl ether to transfer to a sublimation chamber. Sublime product. Characterize final product by TLC (CH2Cl2). Year #1 (Actual Procedure) - Add “active” MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.154 g, 1 mmol) to a pestle. Grind with the mortar until a homogenous mixture of borneol in AMD-silica is obtained, generally 5 to 7 minutes. Transfer this sample via weighing paper into a glass scintillation vial. Cap the vessel and place in the center of a microwave. Microwave on high power for 5 intervals of 20 seconds each, turning the microwave off for 20 seconds in between each interval. Carefully, remove the hot vial. Once the glass is cool, stir the solid in the vial and transfer a small spatula full to a second vial and add 10 drops of diethyl ether. Mix thoroughly and let the solids settle to the bottom. Spot a TLC plate with a) 2% of borneol in diethyl ether, b) 2% of camphor in diethyl ether, and c) your diethyl ether extract. Develop the TLC plate using CH2Cl2 / CH3OH (2:1) as the developing solvent. Use an iodine chamber to observe the spots on the TLC plate. If borneol is still present in your reaction mixture, grind your reaction mixture again in the mortar with the pestle and begin the microwave heating process again. Once the reaction appears to be complete and add 5 mL of CH2Cl2 to the reaction mixture and mix thoroughly to extract the camphor product. Separate the organic layer by vacuum filtration. Dry the CH2Cl2 solution over a 1

Varma, R. S.; Saini, R. K.; Dahiya, R.; “Active manganese dioxide on silica: oxidation of alcohols under solvent-free conditions using microwaves.” Tetrahedron Lett. 1997, 38(45), 7823-7824.

26

Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory small amount of anhydrous sodium sulfate and re-filter to remove the solid. Remove the solvent by rotary evaporation to obtain crude product. Redissolve crude product in a minimum amount of diethyl ether to transfer to a sublimation chamber. Purify the material by vacuum (aspirator) sublimation. Transfer your product to a sealed vial and measure the IR spectrum of your product. WASTE DISPOSAL: Dispose ether solutions from in the Hazardous Organic Waste Container. Dispose the CH2Cl2/CH3OH developing solvent in the Halogenated Organic Waste Container. Dispose of all solid MnO2/silica gel and used TLC plates in the Solid Waste Container. Active Manganese Dioxide on Silica Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details

Score

active manganese dioxide (20-6), silica (20-0) none CH2Cl2 (20-9), anhydrous sodium sulfate (20-4) diethyl ether (20-15) microwave room temperature water purification if water aspirator is used and heat sublimation

14/20 20/20 11/20 5/20 5/5 5/5 3/5 5/5 68/100

Total Score

Year #1 Student questions, answers and new problems. Can we find a better TLC solvent system to replace CH2Cl2? + (10:1, hexane:EtOAc) works perfectly. Can the Et2O for TLC extract be replaced with a better solvent? – hexanes - NO, EtOAc - no, EtOH - no, iPrOH - no. Can we eliminate the final extraction solvent (CH2Cl2 / Et2O)? + place the glass vial in a heated sand bath, product camphor sublimes directly from the reaction mixture. – product collects in the cap. – introduction of new heat source, hot plate / sand bath. Can a test-tube replace the glass vial for final sublimation? + camphor sublimes toward the top of the tube, easier to collect. – product falls back onto the reaction materials. How long is too long? Can we heat the reaction for a longer period and obviate the need to follow the reaction? + 20 sec, 40 sec, 60 sec, 120 sec, camphor to borneol ratio increasing. – brown/white film climbing the side of the glass vial, top most rim of vessel. – white crystals form. + white crystals are product! – microwave oven can overheat. Can we eliminate the separate sublimation step and thereby eliminate the energy required for heating the sand? + upon further heating in the microwave, the camphor sublimes directly in the reaction vessel from the reaction mixture. – yield low due to difficulty in isolating the product from the glass vial. Can a corked test-tube replace the glass vial? + camphor sublimes toward the top of the tube, easier to collect. – product falls back onto the reaction materials. Can a Petri-Dish replace the corked test-tube? + camphor sublimes on top dish, which is easily removed from the bottom, and product isolation is greatly facilitated. How green is the characterization of the final product? Is TLC the best method of analysis? + IR Spectroscopy can be used to easily distinguish borneol from camphor. – the final product is often contaminated with traces of water, which can be misinterpreted as an alcohol. Year #1 (General Procedure – After Improvements) - Grind active MnO2, silica gel, and borneol in a mortar and pestle, until a homogenous mixture is obtained. Transfer this sample into aaa cccaaappppppeeeddd ggglllaaassssss sssccciiinnntttiiillllllaaatttiiiooonnn vvviiiaaalll the bottom of a Petri-dish. Replace Petri dish w cover and place in the center of a household microwave. Microwave at maximum intensity for 100 s. Remove the hot dish carefully. FFFooollllllooow w ttthhheee rrreeeaaaccctttiiiooonnn,,, bbbyyy T T L C C H C m L m R m w TL LC C (((C CH H222C Clll222))) ooofff aaa 111 m mL L dddiiieeettthhhyyylll eeettthhheeerrr eeexxxtttrrraaacccttt ooofff aaa ssspppaaatttuuulllaaa ooofff ttthhheee rrreeeaaaccctttiiiooonnn m maaattteeerrriiiaaalll... R Reeepppeeeaaattt ttthhheee m miiicccrrrooow waaavvveee hhheeeaaatttiiinnnggg aaasss nnneeeccceeessssssaaarrryyy... O O m T L C m m m m L C H C Onnnccceee ttthhheee rrreeeaaaccctttiiiooonnn iiisss cccooom mpppllleeettteee bbbyyy T TL LC C aaannnddd ttthhheee rrreeeaaaccctttiiiooonnn m maaattteeerrriiiaaalll iiisss cccoooooollleeeddd tttooo rrroooooom m ttteeem mpppeeerrraaatttuuurrreee aaadddddd 555 m mL L ooofff C CH H222C Clll222... SSSeeepppaaarrraaattteee ttthhheee ooorrrgggaaannniiiccc lllaaayyyeeerrr bbbyyy vvvaaacccuuuuuum m m R m m m m m fffiiillltttrrraaatttiiiooonnn aaannnddd rrreeem mooovvveee ttthhheee sssooolllvvveeennnttt tttooo ooobbbtttaaaiiinnn cccrrruuudddeee ppprrroooddduuucccttt... R Reeedddiiissssssooolllvvveee cccrrruuudddeee ppprrroooddduuucccttt iiinnn aaa m miiinnniiim muuum m aaam mooouuunnnttt ooofff dddiiieeettthhhyyylll eeettthhheeerrr tttooo tttrrraaannnsssfffeeerrr tttooo aaa sssuuubbbllliiim m m m maaatttiiiooonnn ccchhhaaam mbbbeeerrr... SSSuuubbbllliiim meee ppprrroooddduuucccttt... Recover the sublimed camphor from the Petri-dish cover with a razor blade. C C T L C C H C Chhhaaarrraaacccttteeerrriiizzzeee fffiiinnnaaalllppprrroooddduuucccttt bbbyyy T TL LC C (((C CH H222C Clll222)))... Characterize final product by IR Spectroscopy. Year #1 (Final Procedure) Grind active MnO2, silica gel, and borneol in a mortar and pestle, until a homogenous mixture is obtained. Transfer this sample into the bottom of a Petri-dish. Replace Petri-Dish cover and place in the center of a microwave. Microwave at maximum intensity for 100 s. Remove the hot dish carefully. Recover the sublimed camphor from the Petri-dish cover with a razor blade. Characterize final product by IR Spectroscopy. AMD on Silica Year #1 Final Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details active manganese dioxide (20-6), silica (20-0) none none none microwave microwave water purification and heat sublimation Total Score

Score 14/20 20/20 20/20 20/20 5/5 5/5 3/5 5/5 92/100

27

Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory Year #2 (Summary) - Grind active MnO2, silica gel, and borneol in a mortar and pestle, until a homogenous mixture is obtained. Transfer this sample into the bottom of a Petri-dish. Replace Petri-Dish cover and place in the center of a microwave. Microwave at maximum intensity for 100 s. Remove the hot dish carefully. Recover the sublimed camphor from the Petri-dish cover with a razor blade. Characterize final product by IR Spectroscopy. Year #2 (Actual Procedure) - Add 'active' MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.31 g, 1 mmol) to a pestle. Grind with the mortar until a homogenous mixture of borneol in AMD-silica is obtained, generally 5 to 7 minutes. Transfer this sample via weighing paper into a pile in the center of a glass Petri dish Bottom. Place the Petri Dish Cover on top and place in the center of a microwave. Microwave on high power for 5 intervals of 20 seconds each, turning the microwave off for 20 seconds in between each interval. Open the microwave oven and allow the hot Petri Dish to cool undisturbed and covered for 3 to 4 minutes. Once the Petri Dish cover is cool to the touch carefully lift the cover, turn it upside down in one hand and remove the Petri Dish bottom from the microwave with the other hand. Do you observe sublimed product on the Petri Dish Cover? How can you determine the purity of the material you collected? Are there 1, 2, 3 or more components in the isolated material? How many would you expect? Is borneol still present in your reaction mixture? If you material is a single component, how can you determine the identity of the material you collected? If borneol is still present in your reaction mixture, grind your reaction mixture again in the mortar with the pestle and begin the microwave heating process again. AMD on Silica Year #2 Start Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details active manganese dioxide (20-6), silica (20-0) none none none microwave microwave water purification and heat sublimation Total Score

Score 14/20 20/20 20/20 20/20 5/5 5/5 3/5 5/5 92/100

Year #2 Student questions, solutions and new problems. Can we prevent the microwave from overheating? + a beaker of water absorbs excess energy in the microwave. – but increases the -OH stretch in the IR spectrum of the product. Can we prevent the microwave from overheating? + a beaker of alumina absorbs excess energy and does not increase the water content in the camphor product. Can we diminish the water signal in the IR of the camphor product? + drying the silica gel and the MnO2 before use decreases water in the camphor product. Can we maximize the yield of camphor by placing an ice cold Erlenmeyer on top of the Petri-dish cover?– ice cold Erlenmeyer does not appear to increase % yield, but increases the –OH stretch in the IR spectrum of the product. Can we maximize the yield of camphor by using a Petri-dish with a smaller thickness to decrease the distance between the reaction medium and the product collection vessel? – decreasing the distance increases the amount of MnO2 that is “carried-up” with the sublimed camphor product. Can we increase the purity of the sublimed camphor by increasing the distance between the reaction medium and the product collection vessel? + increasing the distance decreases the amount of MnO2 in the product + appears to increase the yield. Can we decrease the amount of MnO2 that is “carried-up” with the sublimed camphor product, by adding a thin layer of pure silica gel over the reaction medium? + sublimed material slightly cleaner, – yield decreases. Can we minimize the amount of MnO2 that is “carried-up” with the sublimed camphor product, by increasing the particle size? Can we simply shake the reagents together instead of grinding them? – the sublimed material is predominantly borneol instead of camphor when the reagents are shaken together instead of ground. Can we create a semi-continuous reaction vessel by layering the MnO2-silica over the borneol? – no camphor is isolated. Can the same reaction be used for the conversion of other alcohols? + norborneol can be converted to norcamphor Does freshly prepared MnO2 “work better” than “store bought” MnO2? – MnO2 from Aldrich behaves identically to freshly prepared MnO2 Can we increase the yield of camphor by spreading out the reaction medium on the bottom Petri-dish? Results inconclusive - yield improves, yield decreases, yield remained the same Can we increase the yield of camphor by piling the reaction medium in the center of the Petri-dish? Results inconclusive - yield improves, yield decreases, yield remained the same? Questions remaining after lab concluded Year #2: Is the reaction stoichiometric or catalytic? If the reaction is catalytic, can the reaction medium be used again to produce more camphor if more borneol is added? If the reaction is not catalytic, can the oxidant be regenerated? If the reaction is catalytic, how many times can the reaction medium be reused? What is the optimal heating time to produce camphor, while minimizing the sublimation of the starting borneol? Does the particle size of the silica gel matter? Can the reaction product ratio be followed by GC/MS? Can the reaction product ratio be determined by 1H NMR? How can we improve the percent yield of the reaction? The yields are low, but the microwave keeps overheating. Can we use a microwave with adjustable energy levels? Can the reaction be followed by GC/MS?

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Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory Year #3 Conclusions: + A beaker of dry ice atop the Petri Dishes, increases condensation of product by cooling the surface without addition of water. + Reaction is not catalytic. + Adding a drying agent such as anhydrous magnesium sulfate to the reaction mixture decreases yields but eliminates water in the product. + Used manganese dioxide silica mixture, can not be reused. + Many different reactor designs can be used effectively. + The particle size of the silica gel does not cause a statistically significant increase in yield or purity of camphor. + The reaction product ratio can be followed by GC/MS using a standard GowMac GC using temperature settings typically suited for the separation of cyclohexane and toluene. + The presence of borneol in the camphor product down to a 5% can be observed by 1H NMR (90 MHz, EFT Anasazi). + The yield of camphor can increase from 12 - 15% to 85 - 92% while still maintaining a 90 - 95% purity level by heating the reactor directly on a hotplate, by carefully monitoring the temperature. (Best temperature “program”: 25oC to 165oC over ~5 min.; hold at 165oC for 10 min.; ramp up to 200oC over 5 min. and hold at 200oC for 10 min.). + Better reactor can be designed for hotplate reaction. Year #3 (Final Procedure) - Mix 'active' MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.31 g, 1 mmol) with a spatula for 5 minutes in a small beaker. Transfer this sample into a pile in the center of a large watch glass. Place an inverted glass powder funnel on top with a small watch glass covering the end and place on top of the warm hot plate. Best temperature “program”: 25oC to 165oC over ~5 min.; hold at 165oC for 10 min.; ramp up to 200oC over 5 min. and hold at 200oC for 10 min.). Weigh the funnel and the small watch glass separately. The combined result is your yield. Run TLC/IR/NMR/GC on your product to check the purity. The melting point of the product can be determined by a sealed capillary tube melting point determination AMD on Silica Final Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details active manganese dioxide (20-6), silica (20-0) none none none hot plate – 15 minutes hot plate – 15 minutes hot plate – 15 minutes sublimation Total Score

Score 14/20 20/20 20/20 20/20 3/5 3/5 3/5 5/5 87/100

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Student Handout: Greening the Oxidation of Borneol to Camphor 1. A Guided-Inquiry Investigation into Green Metrics Concepts: Oxidation, catalysts, solid-phase synthesis, solvent-free synthesis, sublimation, green chemistry, microwave-assisted reactions, conservation of reagents, conservation of energy, materials safety data sheet. Goals: In this guided-inquiry investigation you will be introduced to the field of green chemistry and the metrics developed thus far to evaluate the “greenness” three different methods to convert a secondary alcohol, borneol, to a ketone, camphor. Introduction: Concepts of environmental stewardship pervade our culture and society but are often noticeably absent in our chemistry curriculum. By the mid 1970's, the notion that 'the solution to pollution was dilution,' gained widespread acceptance. Nearly 30 years later, the implications of our actions are widely apparent, and a number of chemists are finally adopting practices that are 'greener' or more environmentally friendly. Green Chemistry, or chemistry that is more 'benign-by-design,' can be best understood by considering the 'Twelve Principles of Green Chemistry, as outlined by Paul Anastas and John Warner in 1998.2 THE 12 PRINCIPLES OF GREEN CHEMISTRY 1. 2. 3.

It is better to prevent waste than to treat or clean up waste after it is formed. Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product. Wherever practicable, synthetic methodologies should be designed to use and generate substances that possess little or no toxicity to human health and the environment. 4. Chemical products should be designed to preserve efficacy of function while reducing toxicity. 5. The use of auxiliary substances (e.g. solvents, separation agents, etc.) should be made unnecessary wherever possible and, innocuous when used. 6. Energy requirements should be recognized for their environmental and economic impacts and should be minimized. Synthetic methods should be conducted at ambient temperature and pressure. 7. A raw material of feedstock should be renewable rather than depleting wherever technically and economically practicable. 8. Unnecessary derivatization (blocking group, protection/deprotection, temporary modification of physical/chemical processes) should be avoided whenever possible. 9. Catalytic reagents (as selective as possible) are superior to stoichiometric reagents. 10. Chemical products should be designed so that at the end of their function they do not persist in the environment and break down into innocuous degradation products. 11. Analytical methodologies need to be further developed to allow for real-time, in- process monitoring and control prior to the formation of hazardous substances. 12. Substances and the form of a substance used in a chemical process should be chosen so as to minimize the potential for chemical accidents, including releases, explosions, and fires

As a student in a classroom laboratory, most of the experiments are fully prepared to perform in a cookbook fashion. These expository-based laboratories, which only encourage students to reproduce results, do not adequately train chemistry professionals. Most of the research in chemistry is far from 'cookbook;' the majority of time is spent planning and making decisions about the chemical transformations that are to be done. While you are learning the tools of organic chemistry, by studying various chemical transformations, you must realize that you must concomitantly make informed decisions on how to apply these tools, specifically by choosing the reactions and conditions that are 'best' for a given transformation. Of course, 'best' is an entirely subjective qualifier and herein we will learn yet another set of tools (the 12 Principles of Green Chemistry) to evaluate conditions for a given chemical transformation.

2

Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford University Press: New York, 1998.

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For example, herein, we wish to explore the chemistry of the reaction sequence shown in Scheme 1, but how do we decide on the exact experimental conditions to use for this transformation? What factors do we need to consider? Take a moment to list the most important factors you should consider in the transformation below. CH3

CH3

CH3

CH3

O

CH3

oxidation H OH

CH3

camphor

borneol

Scheme 1. Oxidation of borneol to camphor. Chromic acid, sodium dichromate, potassium permanganate, manganese dioxide and sodium hypochlorite are just a few of the oxidizing agents that have been routinely used to convert alcohols to carbonyl compounds. Typically, choosing the 'best' reagent depends on such factors as the starting alcohol, specificity of the reagent, efficiency, cost, convenience, and the associated hazards involved. For example, one might choose an oxidant because it is highly specific for one of the alcoholic functionalities present in a polyfunctional molecule, even though the oxidant may be very expensive. On the other hand, a very inexpensive nonspecific oxidant may be more suitable for the bulk oxidation of an inexpensive and abundant alcohol that is commercially available. While cost and efficiency has often been the bottom line, one must also consider all of the implications of the pathway that is chosen. Lets consider three different schemes and procedures that could be used to oxidize borneol to camphor, and see how the 12 Principles of Green Chemistry could impact our decision of which pathway to choose: NaCr 2O7 a.)

borneol

H2SO 4

camphor

a.) Sodium dichromate:3 Dissolve 2.0g of sodium dichromate dihydrate in 8 mL of water, and carefully add 1.6 mL of concentrated sulfuric acid with an eyedropper. Place the oxidizing solution in an ice bath. While this solution is cooling, dissolve 1.0g of racemic borneol in 4 mL of ether in a 25-mL NaOCl Erlenmeyer flask and cool it in an ice bath. Remove mL of the sodium dichromate oxidizing mixture you have prepared, and slowly add it b.) 6 borneol camphor with an eyedropper to the cold ether solution over 10 minutes. SwirlCH the3COOH reaction mixture in the ice bath between additions and continue swirling for an additional 5 minutes following the final addition of oxidation. Pour the mixture into a separatory funnel and rinse the Erlenmeyer flask, first with a 10-mL portion of ether and then with 10 mL of water. Add both the rinsings to the separatory funnel. Complete the removal of the aqueous phase and pour the ether layer into a storage vessel. Return the aqueous layer to the separatory funnel and extract MnO it with two successive 10-mL portions of ether. Each time add the ether phase 2 to the storage vessel and return the aqueous layer to the camphor c.) borneol separatory funnel. Return the combined either extracts to the separatory funnel and extract them with 10 mL of 5% sodium bicarbonate. A silica gel small amount of solid material may be produced at the interface. Carefully remove the lower aqueous layer and as much of this solid as possible without losing the ether layer. Finally, wash the ether layer with 10 mL of water and drain the lower aqueous layer. The ether layer contains the desired camphor. Pour it out of the top of the separatory funnel, decanting it away from any solids. Dry the ether layer thoroughly with a small amount (about 1g) of anhydrous magnesiumNaCr sulfateO in a stoppered Erlenmeyer flask. Swirl the flask gently until the 2 7 ether phase is clear. Decant the dry ether phase into a beaker and evaporate the solvent in the hood on a steam bath (using a boiling stone) or camphor a.)evaporated borneoland a solid has appeared, with a stream of dry air. When the ether has remove the flask from the heat source immediately, H2SO 4 otherwise the product may sublime prematurely and be lost. Weigh the product. At least 0.4g of crude camphor should be obtained. Purify the material by vacuum (aspirator) sublimation.

NaOCl b.)

borneol

camphor CH3COOH

b.) sodium hypochlorite:4 To a 5-mL conical vial add 0.180g of racemic borneol, 0.50 mL of acetone, and 0.15 mL of glacial acetic acid. After adding a spin vane to the MnO 2 vial, attach an air condenser and place the conical vial in a water bath at about 45 ˚C. It is important that the temperature of the water bath camphor

c.)

3

borneol

silica gel

Pavia, D. L.; Lampman, G. M.; Kriz, G. S. Introduction to Organic Laboratory Techniques; Saunders Golden Sunburst Series; Saunders College Publishing: Fort Worth, TX, 1990. 4 Pavia, D. L.; Lampman, G. M.; Kriz, G. S.; Engel, R. G. Introduction to Organic Laboratory Techniques, a Small Scale Approach; Third Edition; Saunders College Publishing: Fort Worth, TX, 1999.

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Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory remain between 40-50˚C during the entire reaction period. Stir the mixture until the borneol is dissolved. While continuing to stir the reaction mixture, add drop wise 2.0 mL of a bleach solution (5.25% sodium hypochlorite) through the top of the air condenser over a period of about 30 minutes. When the addition is complete, stop stirring the mixture and remove a few drops of the bottom aqueous layer with a Pasteur pipette. Transfer this liquid onto a wet piece of starch-iodide indicator paper to determine if a sufficient amount of bleach has been added. A blue-black color due to the formation of the starch-iodine complex indicates that an excess of hypochlorite is present. If there is no color change, add an additional 0.2 mL of bleach to the reaction mixture, stir for several minutes, and repeat the starch-iodide test. Continue this process until the paper turns blue. Stir the mixture for 10 minutes after the last addition of bleach and repeat the starch-iodide test. If it is negative (absence of blue-black color), add an additional 0.2 mL of bleach. Whether additional bleach was added or not, allow the reaction to continue for 10 minutes more. When the reaction time is complete, allow the mixture to cool to room temperature. Remove the air condenser and add 1.0 mL of CH2Cl2 to extract the camphor. Cap the vial and shake well with venting. Remove the spin vane with forceps and rinse the spin vane and forceps with a few drops of CH2Cl2. Using a filter tipNaCr pipette, the lower CH2Cl2 layer into another 5-mL conical vial. 2Otransfer 7 Extract the aqueous layer with a second 1.0-mL of CH2Cl2 layers with 1.0 mLcamphor of saturated sodium bicarbonate solution. Stir the liquid a.) portion borneol with a stirring rod or spatula until bubbling produced by the formationHof2SO carbon 4 dioxide ceases. Cap the vial and shake with frequent venting to release any pressure produced. Transfer the lower CH2Cl2 layer to another container and remove the aqueous layer. Return the CH2Cl2 layer to the vial and wash this solution successively with 1.0 mL of saturated sodium bisulfite and 1.0 mL of water. Using a dry filter tip pipette, transfer the CH2Cl2 to a dry test tube or conical vial. Add three to four microspatula-fulls of granular anhydrous sodium sulfate and let dry for NaOClflask, transfer the CH2Cl2 solution to the flask. Evaporate the 10-15 minutes with occasional shaking. After taring a 10-mL Erlenmeyer camphor solvent in the hood with a gentle stream of b.) dry airborneol or nitrogen gas while heating the Erlenmeyer flask in a sand bath at 40-50 ˚C. As an CH3When COOH alternative, leave the flask in the hood until the CH2Cl2 has evaporated. all the liquid has evaporated and a solid has appeared weigh the flask to determine the weight of your crude product and calculate the percentage yield. Purify all material by vacuum (aspirator) sublimation. Determine the melting point in a sealed capillary tube to prevent sublimation.

c.)

borneol

MnO 2

camphor

silica gel c.) active manganese dioxide on silica Add “active” MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.154 g, 1 mmol) to a pestle. Grind with the mortar until a homogenous mixture of borneol in AMD-silica is obtained, generally 5 to 7 minutes. Transfer this sample via weighing paper into a glass scintillation vial. Cap the vessel and place in the center of a microwave. Microwave on high power for 5 intervals of 20 seconds each, turning the microwave off for 20 seconds in between each interval. Carefully, remove the hot vial. Once the glass is cool, stir the solid in the vial and transfer a small spatula full to a second vial and add 10 drops of diethyl ether. Mix thoroughly and let the solids settle to the bottom. Spot a TLC plate with a) 2% of borneol in diethyl ether, b) 2% of camphor in diethyl ether, and c) your diethyl ether extract. Develop the TLC plate using CH2Cl2 / CH3OH (2:1) as the developing solvent. Use an iodine chamber to observe the spots on the TLC plate. If borneol is still present in your reaction mixture, grind your reaction mixture again in the mortar with the pestle and begin the microwave heating process again. Once the reaction appears to be complete and add 5 mL of CH2Cl2 to the reaction mixture and mix thoroughly to extract the camphor product. Separate the organic layer by vacuum filtration. Dry the CH2Cl2 solution over a small amount of anhydrous sodium sulfate and re-filter to remove the solid. Remove the solvent by rotary evaporation to obtain crude product. Redissolve crude product in a minimum amount of diethyl ether to transfer to a sublimation chamber. Purify the material by vacuum (aspirator) sublimation. Transfer your product to a sealed vial and measure the IR spectrum of your product. WASTE DISPOSAL: Dispose ether solutions from in the Hazardous Organic Waste Container. Dispose the CH2Cl2/CH3OH developing solvent in the Halogenated Organic Waste Container. Dispose of all solid MnO2/silica gel and used TLC plates in the Solid Waste Container.

What is the toxicity of all of the chemicals used in the synthetic transformation? Typically, a.) sodium dichromate or b.) sodium hypochlorite (bleach) to used in the oxidation of borneol to camphor. Chromium (VI) is a recognized carcinogen and a high priority persistent, bioaccumulative, toxic (PBT) chemical. According to the US EPA, PBT's do not readily break down in the environment, are not easily metabolized, may accumulate in human or ecological food-chains through consumption or uptake and may be hazardous to human health or the environment. (Not all forms of chromium are hazardous. Chromium (III) is an essential nutrient that helps the human body utilize sugar, protein and fat, by activating insulin in tissues.) While, chromium wastes can be carefully collected and treated, waste production should always be reduced or completely avoided if possible, especially when proven hazardous to humans or the environment. Our choice to use sodium dichromate also necessitates that it be produced, shipped and eventually treated or stored afterward. Therefore, we are dictating not only our but also several other people's potential exposure to the chemical. While route b is a much better alternative than route a, primarily because sodium hypochlorite (bleach) is much more innocuous than sodium dichromate, it is not without its potential problems and hazards. Notably, small amounts of chlorine gas can be emitted from the reaction mixture, the reaction must be carried out in a well-ventilated area, and commercial bleach, the source of sodium hypochlorite, contains measurable amounts of mercury. Which of the 12 Principles of Green Chemistry and associated with the discussion above?_____________________ Are catalytic or stoichiometric reagents being used? Sodium dichromate and sodium hypochlorite are both stoichiometric not catalytic reagents - a reagent that increases the effective rate of the reaction without being itself consumed. As catalysts are not consumed in the

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reaction, only a catalytic amount (often less than 1% / mol) is needed. Manganese dioxide supported on silica gel has been reported to be catalytic in certain reactions, but not yet for the oxidation of alcohols.5 Furthermore, manganese dioxide supported on silica gel is also a solid-supported reagent, which, in general has the advantage over solution phase reagents because the isolation of the product is often facile and the reagent may then be reused easily if it can be regenerated. Both of these properties add to the greenness of a process by reducing solvents and chemical waste. Which of the 12 Principles of Green Chemistry and associated with the discussion above?_______ What auxiliary substances, such as solvents, drying agents, etc., are needed? The sodium dichromate procedure uses ether as the solvent during the reaction and uses several washes of fresh ether and sodium bicarbonate during workup. If the sodium hypochlorite method is used, acetone and acetic acid are used during the reaction period and the product is extracted with CH2Cl2, washed with sodium bicarbonate, and dried over sodium bisulfate. The activated manganese dioxide route, is accomplished completely in the solid state in the absence of solvent, however, CH2Cl2 is utilized to extract the product from the reaction mixture and diethyl ether is utilized to test whether the reaction is complete. Which of the 12 Principles of Green Chemistry and associated with the discussion above?_____________________ Can we minimize the energy required in the transformation? Energy use also has environmental and economical costs. The sodium dichromate procedure requires the use of ice and the hypochlorite experiment uses a conventional heating source (40-50°C) for 50 minutes. Heating and cooling requirements are a form of energy expenditure and should be reduced when possible. The activated manganese dioxide route requires much less energy than a conventional heating source, because it is run in a microwave oven. In microwaves, thermal boundary layers are minimized while internal heating is maximized, homogenous heating optimizes the purity of the reaction, and the heat source may be started and ceased instantaneously. Microwaves can decrease the reaction time of an experiment and therefore decrease its energy requirement. Which of the 12 Principles of Green Chemistry and associated with the discussion above?_____________________ With the above considerations, the activated manganese dioxide route qualitatively appears more favorable than either the sodium dichromate or sodium hypochlorite procedures. However, we can begin to quantify and compare the procedures with the aid of a rubric, a systematic tool that can guide the qualitative critique and analysis of the various methods used, and achieve a deeper shade of green, without stipulating the absolute goal. A rubric is also able to constantly evolve with the greening process. procedure Oxidant / Reactants* Solvent* reaction isolation purification

Details

GIV = (20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements)) or GIV-F GIV = (20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements)) or GIV-F GIV = (20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements)) or GIV-F GIV = (20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements)) or GIV-F “Brown” (0 – 1) “Green” (2 – 3) “Greener” (4 – 5) Ceramic hot-plate, heating manifold, Ceramic hot-plate, heating manifold, Microwave energy, Energy reaction Bunsen-burner: long heating time. Bunsen-burner: short heating time. minimal or no heating. Ceramic hot-plate, heating manifold, Ceramic hot-plate, heating manifold, Microwave energy, isolation Bunsen-burner: long heating time. Bunsen-burner: short heating time. minimal or no heating. Ceramic hot-plate, heating manifold, Microwave energy, purification Ceramic hot-plate, heating manifold, Bunsen-burner: long heating time. Bunsen-burner: short heating time. minimal or no heating. e.g. column chromatography e.g. distillation e.g. crystallization / Purification Method sublimation *The oxidant / reactant / solvent with the lowest number is included in rubric evaluation for that category. Total Score

score #/20 #/20 #/20 #/20 #/5 #/5 #/5 #/5 #/100

Table 1. A generalized rubric for evaluating the greenness of a procedure. The higher the total score the “greener” the procedure.

The 12 principles of Green Chemistry guide the process of greening an experiment, but do not provide a quantitative measure of green. Metrics 6 have been developed, thus far, to provide a tool to compare the theoretical reaction efficiency (percent atom economy),7 amount of waste generated (E Factor),8 and reaction efficiency with 5

Stavrescu, R.; Kimura, T.; Fujita, M.; Vinatoru, M.; Ando, T. Synth Commun. 1999, 29(10), 1719 – 1726. D. J. C. Constable, A. D. Curzons, V. L. Cunningham, Green Chem. 2002, 4, 521 – 527. 7 B. M. Trost, Science, 1991, 254, 1471 – 1477; B. M. Trost, Acc. Chem. Res., 2002, 35, 695 – 705. 8 R. A. Sheldon, Chemtech, 1994, 24, 38 – 47. 6

33


relative hazards of the waste stream included (effective mass yield)9 of all potential procedures that are considered. However, these metrics focus heavily on efficiency by measuring atoms incorporated, waste generated or desired product produced versus hazardous waste generated, respectively. These metrics, while informative and necessary, are cumbersome for a novice green chemist and not easily applied to the process of greening an experiment The rubric above evaluates the oxidant/reagents, the solvents and energy involved in the reaction, isolation and purification steps as well as the general purification method, Figure 1. Oxidants, reagents and solvents are rated semi-quantitatively and are based upon the “scale” National Fire Protection Association (NFPA) Rating (Health + Fire + Reactivity)) and the number of “Risk” and “Safety Phrases” listed in the Regulatory Information section of a materials safety data sheet (MSDS). The flaw in the rubric’s current design is that all risks and safety phrases are given equal weight. Obviously, Risk Phrase 22 (R22) (harmful if swallowed) ideally should not be equated with R45 (may cause cancer) or R46 (may cause heritable genetic damage). More in depth analysis and evaluation should consider the USNLM’s Toxicology Data Network10 and NIOSH’s documentation for immediately dangerous to life or health (IDLH) concentrations.11 The chemicals utilized in each experiment account for 80% of the total rubric evaluation. The remaining 20% pertains to the energy and purification methods used and significantly more qualitative. The higher the overall rubric-score the deeper the “shade of green,” for an evaluated reaction scheme. The rubric outlined above requires the assignment of a “green-index-value” for all chemicals used. The higher the “green-index-value” the greener the reagent. “Green-index-values” are calculated according to the formula below: 20 – (NFPA Rating Total (H+F+R)) – (#Risk Statements) – (# of Safety Statements) Calculate how hazardous ethanol is to work with in the laboratory, by calculating its green-index-value. You will need to find the Materials Safety Data Sheet (MSDS) for ethanol. A MSDS can be found for every chemical manufactured. Those produced by Fischer Scientific on the WWW are highly recommended. The Fisher MSDS for ethanol can be found on the WWW at: https://fscimage.fishersci.com/msds/89308.htm Reagents ethanol

CAS # [64-17-5]

Green Index Value

Even though ethanol is considered a green solvent, the green-index-value falls below 14, a breaking point in the hazard scale separating hazardous and less hazardous chemicals. Recalculate the green-index-value removing all NFPA ratings, risk statements, and safety statements that involve the flammability of ethanol. You should notice a dramatic increase in the green-index-value for ethanol. Reagents ethanol

CAS # [64-17-5]

Green Index Value

9

T. Hudlicky, D. A. Frey, L. Koroniak, C. D. Claeboe, L. E. Brammer, Green Chem., 1999, 1, 57 – 59. United States National Library of Medicine Toxicology Data Network: http://toxnet.nlm.nih.gov/ (accessed June 2007). 11 National Institute for Occupational Health and Safety (NIOSH) documentation for immediately dangerous to life or health concentrations (IDLH): NIOSH Chemical Listing and Documentation of Revised IDLH Values (as of 3/1/95), http://www.cdc.gov/niosh/idlh/intridl4.html (accessed June 2007). 10

34


Evaluating the “Greenness” of a Reaction Step 1. Calculate all of the green-index-values for all chemicals involved. Review each of the three procedures for the oxidation of borneol to camphor and calculate all of the green index values (GIV) for all chemicals involved. As flammability in the laboratory is one hazard that can be more easily controlled, you might consider calculating the hazard value with and without the flammability values, GIV-F. For example ethanol is considered a “green” solvent, but as noted above the hazard value we calculate is quite low, indicating a hazardous reagent. Step 2. If the green GIV or GIV-F is below 14 we must consider that the chemical is non-benign and we need to consider the grams used in a reaction to calculate the % effective mass yield later on.

GIV

CAS #


*considering flammability (GIV-F)


sodium dichromate

[7789-12-0]

21195.htm

20-(3-0-0)-(12)-(4)=1

2.0


[7664-93-9]

22350.htm

diethyl ether

[60-29-7]

90868.htm

sodium bicarbonate

[144-55-8]

20970.htm

magnesium sulfate

[7487-88-9]

13525.htm

[67-64-1]

00140.htm

[64-19-7]

00120.htm

sodium hypochlorite

[7681-52-9]

40179.htm


[7681-52-9] [7439-97-6]

96252.htm

dichloromethane

[75-09-2]

89820.htm

sodium bicarbonate

[144-55-8]

20970.htm

sodium bisulfite

[10034-88-5]

20995.htm


[7757-82-6]

21630.htm

Reagents sodium dichromate

sodium hypochlorite acetone glacial acetic acid

20-(1-3-0)-(4)-(3)=9* 20-(1-X-0)-(3)(2)=14

20-(0-0-0)-(2)-(3)=15 15-(3-0-0)-(2)-(2)=8

active manganese dioxide active MnO2

[1313-13-9]

13610.htm

silica gel

[112926-00-8]

20665.htm

diethyl ether

[60-29-7]

90868.htm

dichloromethane

[75-09-2]

89820.htm

20-(1-4-1)-(5)-(4)=5* 20-(1-X-1)-(4)-(2)=12

Table 2. GIV-F values for all chemicals used in the three oxidation procedures.

35


Step 3. Evaluating the “Greenness” of a Reaction Use the GIV-F data to determine which procedure, as written, is the greenest using the rubrics below, Table 3. The rubric for the sodium dichromate procedure has been completed to act as a guide. The overall “score” for a given category is determined by the lowest green-index-value for that category. For example, in the sodium dichromate procedure the Oxidant/Reactants include sodium dichromate (1), concentrated sulfuric acid (11) and water (20). The overall score for the Oxidant/Reactants category for the sodium dichromate procedure, therefore, would be 1/20.

sodium dichromate Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details Score sodium dichromate (20-19), sulfuric acid (20-9), water 1/20 diethyl ether (20-15) 5/20 diethyl ether (20-15), sodium bicarbonate, magnesium sulfate 5/20 none 20/20 ice 5/5 room temperature 5/5 materials used for water purification (if water aspirator is used) and heat 5/5 sublimation 3/5 Total Score 49/100

sodium hypochlorite Oxidant/Reactants Solvent Reaction Isolation purification Energy Reaction Isolation purification Purification Method

Details

Total Score active manganese dioxide on silica Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details

Score /20 /20 /20 /20 /5 /5 /5 /5 /100 Score

Total Score

/20 /20 /20 /20 /5 /5 /5 /5 /100

36


Step 4: Assessing the efficiency of Oxidation reactions using green metrics Green metrics provide a tool to compare the theoretical reaction efficiency (percent atom economy), amount of waste generated (E Factor), and reaction efficiency with relative hazards of the waste stream (effective mass yield) of all potential procedures. 1. Begin by writing a balanced equation for each reaction. a) sodium dichromate:

b) sodium hypochlorite:

c) active manganese dioxide on silica:

2. Atom economy is measure of the efficiency of your planned reaction. Unlike percent yield or percent recovery, atom economy is a theoretical calculation that does not require the reaction to be run. To calculate atom economy the molecular weight of the products are divided by the molecular weight of all of the reagents / starting materials used to produce the product, see the formulas below. Calculate the percent atom economy for all three reactions. a) sodium dichromate: # MW & products % ( )100 = % " MW ( reagents ' $

! b) sodium hypochlorite: # MW & products % ( )100 = % " MW ( reagents ' $

!

37


c) active manganese dioxide on silica: # MW & products % ( )100 = % " MW ( reagents $ '

!

d) Given the formula above, which is more desirable percent atom economy – a high percent or a low percent? Explain.

e) What are the theoretical limits of atom economy? Can you ever achieve 0% or 100% atom economy?

f) How does the percent atom economy for all three reactions compare?

g) Which reaction pathway is most ‘atom economical?’

h) Using specific information above explain the following question: What does it mean for a reaction to be atom economical?

i) The formula for percent atom economy does not include solvents or other chemicals used in the isolation and purification of the desired product? In your opinion, should these chemicals be included when calculating the percent atom economy? If so, propose a new formula for percent atom economy to include them.

38


3. Effective mass yield accounts for the relative toxicity as well as the reaction efficiency by focusing only on the hazardous components of the waste. Unlike percent atom economy, which is based upon the molecular, effective mass yield, uses the actual masses of reagents used and products generated in the reaction. Similar to percent atom economy effective mass yield also assumes that you will generate a 100% yield. Calculate the effective mass yield for all the reactions. a) sodium dichromate: NOTE: Calculate effective mass yield assuming 100% yield.

# & % Massproduct ( % Mass ( )100 = %" nonbenign ( material ' $

! b) sodium hypochlorite: NOTE: Calculate effective mass yield assuming 100% yield. # & % Massproduct ( % Mass ( )100 = %" nonbenign ( material ' $

! c) active manganese dioxide on silica: NOTE: Calculate effective mass yield assuming 100% yield. # & % Massproduct ( % Mass ( )100 = %" nonbenign ( material ' $

! d) How does the effective mass yield for all three reactions compare?

e) Which reaction pathway is most ‘effective,’ based upon your calculation of effective mass yield?

39


f) The formula for effective mass yield does not include solvents or other chemicals used in the isolation and purification of the desired product? In your opinion, should these chemicals be included when calculating the effective mass yield? If so, propose a formula for effective mass yield to include them.

g) In your opinion, does the calculation for effective mass yield, really reflect the effective mass yield of a reaction?

h) In your opinion, which is a better measure of the ‘greenness’ of a reaction, percent atom economy or effective mass yield? Justify your answer.

4. Calculation of E-Factor: E-Factor is defined as the grams of byproduct divided by the grams of product. The E-Factor provides a chemist with a measure of how many grams of waste is produced for every gram of product. Using the tables below, calculate the E-Factor for all the reactions. a) sodium dichromate: Item

Product in grams

Byproduct in grams

E-Factor

camphor sodium dichromate sulfuric acid (concd.) diethyl ether sodium bicarbonate anhyd. magnesium sulfate water Total

b) sodium hypochlorite 40

Supplemental Information – Involve students in the decision making process: oxidation of borneol to camphor in the teaching laboratory Item

Product in grams

Byproduct in grams

E-Factor

Product in grams

Byproduct in grams

E-Factor

camphor acetone glacial acetic acid sodium hypochlorite dichloromethane sat. sodium bicarbonate sat. sodium bisulfite water sodium sulfate anhydrous Total

c) active MnO2 on silica: Item camphor active MnO2 silica gel dichloromethane anhydrous sodium sulfate Total

d) Given two reactions that have E-Factors of 65 and 6.5, which reaction is more benign or ‘greener?’

e) Based upon your calculation of the E-Factor for all three reactions, discuss which reaction is ‘greener.’

f) In your opinion, which is a better measure of the ‘greenness’ of a reaction, percent atom economy, effective mass yield, or the E-Factor? Justify your answer.

g) Which metric will give you the best measure of the greenness for your reaction next week?

41


5. Economic Evaluation – When was the last time you considered the cost of a reaction you performed in the laboratory? As students in academia, it is perhaps the least of your considerations when performing an experiment in the laboratory. However, economics is perhaps one of the most crucial considerations for a chemist in industry when choosing between several different reaction schemes. Using the cost of the reagents for all three reactions provided below (from the 2007 Aldrich Catalog), first calculate the cost of purchasing the chemicals for each reaction as they are written in the procedures above. a) sodium dichromate: Item

CAS #

Quantity

Cost

Cost / g or mL

borneol

[464-45-9]

$156.00/500g

sodium dichromate

[7789-12-0]

$101.00/500g


[7664-93-9]

$28.30/500mL

diethyl ether

[60-29-7]

$41.9/L

sodium bicarbonate

[144-55-8]

$17.10/500g


[7487-88-9]

$53.20/500g

water

[7732-18-5]

Cost / reaction

Total cost to perform the experiment

b) sodium hypochlorite Item

CAS #

Quantity

Cost

borneol

[464-45-9]

$156.00/500g

acetone

[67-64-1]

$25.30/L

glacial acetic acid

[64-19-7]

$27.20/500mL

sodium hypochlorite

[7681-52-9]

$32.30/500mL

dichloromethane

[75-09-2]

$24.20/500mL

sodium bicarbonate

[144-55-8]

$17.10/500g

sodium bisulfite

[10034-88-5]

$16.70/500g


[7757-82-6]

$30.20/500g

Water

[7732-18-5]

-

Cost / g or mL

Cost / reaction

-

-


c) active MnO2 on silica: Item

CAS #

Quantity

Cost

borneol (1mmol)

[464-45-9]

$156.00/500g

active MnO2 (4mmol)

[1313-13-9]

$165.50/500g


[112926-00-8]

$47.70/100g

diethyl ether

[60-29-7]

$41.9/L

dichloromethane

[75-09-2]

$24.20/500mL

methanol

[67-56-1]

$18.70/500mL


[7757-82-6]

$30.20/500g

Cost / g or mL

Cost / reaction


d) Based upon your calculations which pathway is the most cost effective method to convert borneol to camphor?

42


e) As the reactions are all performed at different scales, the costs are not directly comparable. Normalize cost of each experiment by calculating the Total Cost to perform the experiment per gram borneol oxidized. Which pathway is the most cost effective method to covert 1 gram of borneol to camphor?

f.) The true cost of an experiment must also consider the cost of waste disposal, which often accounts for more than 50% of the cost of manufacturing. Given the following information calculate the total cost to dispose of the waste produced in the experiment and the total cost to dispose of the waste produced in the experiment per gram of borneol oxidized. a) sodium dichromate Quantity / student

Cost of Disposal

[464-45-9], [7789-12-0], [7664-93-9], [144-55-8], [7732-18-5]

50 mL

X/5L

flammable

[60-29-7]

30 mL

X /5L

basic, flammable

[7487-88-9]

1.0 g

X / 500g

Item

Hazard Class

CAS #’s



diethyl ether magnesium sulfate powder traces of diethyl ether and camphor

Cost / g or mL

Cost / reaction


b) sodium hypochlorite Quantity / student

Cost of Disposal

[464-45-9], [67-64-1], [64-19-7], [7681-52-9], [144-55-8], [10034-88-5]

10 mL

X/5 Liters

[75-09-2]

3 mL

X /5 Liters

[7757-82-6]

1g

X / 500g

Item

Hazard Class

CAS #’s

borneol, acetone, glacial acetic acid, sodium hypochlorite, sodium bicarbonate, sodium bisulfite, with traces of mercury

corrosive, strong oxidant, flammable, mercury

dichloromethane

halogenated organic


basic

Cost / g or mL

Cost / student


c) active MnO2 on silica: Quantity / student

Cost of Disposal

[464-45-9], [1313-13-9], [112926-00-8]

1.2 g

X / 500g

halogenated organic

[60-29-7], [75-09-2], [67-56-1]

75 mL

X /5 Liters

basic

[7757-82-6]

0.25g

X / 500g

Item

Hazard Class

CAS #’s



diethyl ether, dichloromethane sodium sulfate anhydrous

Cost / g or mL

Cost / student


43


Final Economic Analysis A. Cost of laboratory experience (per student) (cost to perform / student) + (cost to dispose / student) = B. Total cost of waste based on choice of pathway (per student) (initial cost purchasing “waste-to-be”) + (cost to dispose / student) = “Industrial Scale” To calculate the cost per gram scale (to normalize microscale and normal scale reactions): C. Cost of oxidizing 1 gram of material through this procedure (cost to perform / gram oxidized) + (cost to dispose / gram oxidized) = D. Total cost of waste to oxidize 1 gram of borneol through this procedure (initial cost purchasing “waste-to-be” / gram oxidized) + (cost to dispose / gram oxidized) = E. Economic Efficiency of this pathway per gram of oxidized material: (total cost of waste to oxidize 1 gram of borneol / cost of 1 gram borneol) g) Using the calculations above as your guide to consider both the purchasing of chemicals but also their disposal: • •

identify which reaction pathway is the most cost effective manner to perform the oxidation experiment as a student in the laboratory? identify which reaction pathway is the most cost effective manner to oxidize 1 gram of borneol to camphor?

44


Student Handout: Greening the Oxidation of Borneol to Camphor 2. An Open-Inquiry Experiment Required Reading: Review oxidations of alcohols to aldehydes and ketones in your textbook. Concepts: Oxidation, catalysts, solid-phase synthesis, solvent-free synthesis, sublimation, green chemistry, microwave-assisted reactions, conservation of reagents, conservation of energy, materials safety data sheet. Goals: In this open-inquiry investigation you will use your knowledge of green chemistry and the results of the metrics you calculated in Part 1 to propose one method to green the oxidation of borneol using active manganese dioxide as the oxidant.

oxidation HO borneol

H

reduction O camphor

+ H

OH

isoborneol

HO

H

borneol

Scheme 1. Oxidation of borneol to camphor. 1. Using the 12 principles think of three ways in which you could green the active manganese dioxide on silica procedure. For each of the three examples outline the following: (An example is provided below.) a. What is your idea? Formulate a question or hypothesis you can test. b. How can you test your hypothesis? Outline a procedure that will test your hypothesis. c. What controls will you use to test your hypothesis? d. What data will you collect? e. How will you analyze your data? f. In hindsight, what is your purpose for performing your experiment? g. How will you determine whether your procedure was successful? Example #1: If the manganese dioxide on silica is catalytic, I could reuse the oxidant a second time to prevent waste. (Associated green principles 1 and 9.) a. If the oxidant is catalytic it can used a second, third or fourth time to perform the same reaction. b. If I can reuse the oxidant to perform a second oxidation after completing the reaction the first time with a stoichiometric amount of oxidant and borneol, the experiment suggests the oxidant is catalytic. c. The product of the reaction the first and second time should both produce camphor when the oxidant is reused. d. I must determine the percent yield, purity and identity of the product from the first and second oxidation. e. I can use the product weight to determine the yield, TLC or GC to determine the purity, and IR spectroscopy to determine the identity of the product. f. The purpose of this experiment will be to determine if the oxidant is stoichiometric or catalytic. g. Assuming the product in both the first and second reaction is camphor and the percent yield and purity of the camphor is not radically diminished after the second reaction, it is likely that the product is catalytic. Example #2: In the oxidation of borneol to camphor with active manganese dioxide on silica less energy is expended in the microwave, however, a lower yield of camphor is routinely observed. Can the identical procedure be accomplished by heating the reactants in a loosely capped glass scintillation vial or in a covered Petri dish on a hotplate at 100oC for 20 min? (Associated green principles 1, 2 and 6.) a. A microwave expends less energy, however, the use of a hotplate may increase the percent yield. If the procedure is performed with a hotplate as compared to a microwave, is the percent yield and purity higher?

45


b. If I perform the identical reaction in both the microwave and on the hotplate I can directly compare the percent yield and purity of the product. c. I must use identical amounts of reagents and reactors (vial or Petri dish) so that I may directly compare the percent yield and purity of the product. d. I must determine the percent yield, purity and identity of the product using both a hotplate and a microwave as the heating source. e. I can use the product weight to determine the yield, TLC or GC to determine the purity, and IR spectroscopy to NaCr 2O7 determine the identity of the product. camphor a.)willborneol f. The purpose of this experiment be to determine if a hotplate can produce the same or better percent yields H2SO 4 and purities as compared to a microwave. g. Assuming the product in both reactions is camphor and the percent yield and purity of the camphor is not identical, one heating source produces a better yield and a higher purity of camphor. NaOCl

b.)

borneol

camphor

2. Using the generalized active manganese dioxide CH on silica procedure below, write a complete procedure to test 3COOH one of your three hypotheses that can be completed in one lab period.

c.)

borneol

MnO 2

camphor

silica gel

Add “active” MnO2 (0.348 g, 4 mmol), silica gel (230-400 mesh w/ 600 m2/g, 0.652 g), and borneol (0.154 g, 1 mmol) to a pestle. Grind with the mortar until a homogenous mixture of borneol in AMD-silica is obtained, generally 5 to 7 minutes. Transfer this sample via weighing paper into a glass scintillation vial. Cap the vessel and place in the center of a microwave. Microwave on high power for 5 intervals of 20 seconds each, turning the microwave off for 20 seconds in between each interval. Carefully, remove the hot vial. Once the glass is cool, stir the solid in the vial and transfer a small spatula full to a second vial and add 10 drops of diethyl ether. Mix thoroughly and let the solids settle to the bottom. Spot a TLC plate with a) 2% of borneol in diethyl ether, b) 2% of camphor in diethyl ether, and c) your diethyl ether extract. Develop the TLC plate using CH2 Cl2 / CH3 OH (2:1) as the developing solvent. Use an iodine chamber to observe the spots on the TLC plate. If borneol is still present in your reaction mixture, grind your reaction mixture again in the mortar with the pestle and begin the microwave heating process again. Once the reaction appears to be complete and add 5 mL of CH2 Cl2 to the reaction mixture and mix thoroughly to extract the camphor product. Separate the organic layer by vacuum filtration. Dry the CH2Cl2 solution over a small amount of anhydrous sodium sulfate and re-filter to remove the solid. Remove the solvent by rotary evaporation to obtain crude product. Redissolve crude product in a minimum amount of diethyl ether to transfer to a sublimation chamber. Purify the material by vacuum (aspirator) sublimation. Transfer your product to a sealed vial and measure the IR spectrum of your product. WASTE DISPOSAL: Dispose ether solutions from in the Hazardous Organic Waste Container. Dispose the CH2Cl2/CH3OH developing solvent in the Halogenated Organic Waste Container. Dispose of all solid MnO2/silica gel and used TLC plates in the Solid Waste Container. Pre-Lab Preparation: Review the techniques in your lab manual regarding: thin-layer chromatography (TLC), IR spectroscopy, gas chromatography (GC) and materials safety data sheets MSDS. Write a one-page description (in your own words) summarizing in detail how to use a and b or c: a. TLC to follow the oxidation of borneol to camphor. A satisfactory description would detail the: i. best method for spotting the TLC plate; ii. materials you will spot on the TLC plate; iii. method you would determine the optimal solvent or solvent system to develop the TLC plate; iv. method you will visualize the developed TLC plate; v. method by which you will determine if the oxidation is complete. What controls will you use? b. IR spectroscopy to follow the course of the oxidation of borneol to camphor. A satisfactory description: i. predicts the IR spectrum of the starting material, product and impurities that may form; ii. predicts the IR spectrum of a mixture of the starting material and product; iii. specifies IR cm-1 that can differentiate the starting material, product or impurities; iv. outlines the method by which you will determine if the oxidation is complete.

46


c. GC to follow the course of the oxidation of borneol to camphor. A satisfactory description would: i. describe the melting, boiling or sublimation temperatures of borneol and camphor; ii. describe your reasoning behind the choice of column temperature; iii. describe which compound, borneol or camphor will elute from the column first; iv. describe how you will determine the percentage of borneol and camphor present in the gas chromatogram of a mixture of both; v. provide a sample calculation; vi. briefly describe how gas chromatography can be used to determine if the oxidation is complete. What controls will you use? Procedure In this experiment you will test your hypothesis by performing the oxidation of borneol to camphor using your detailed procedure. Hazards MnO2 is listed as being only harmful if it is inhaled or digested. Given that the reagent is bound to a solid-support the probability of harmful exposure decreases significantly. Minimize the inhalation risk by working in your fume hood. Post-Lab Questions: Evaluating the “Greenness” of Your Reaction Step 1. Calculate all of the green-index-values for all chemicals involved. Calculate all of the green-index-values for all chemicals involved. As flammability in the laboratory is one hazard that can be more easily controlled, you might consider calculating the hazard value with and without the flammability values. For example ethanol is considered a “green” solvent, but as noted above the hazard value we calculate is quite low, indicating a hazardous reagent.

Reagents CAS # your active manganese dioxide procedure


active MnO2

[1313-13-9]

13610.htm

silica gel

[112926-00-8]

20665.htm

green-index-value *considering flammability


Step 2. If the green-index-value is below 14 we must consider that the chemical is non-benign and we need to consider the grams used in a reaction to calculate the % effective mass yield later on.

47


Step 3. Evaluating the “Greenness” of a Reaction Use the green-index-value data to determine which procedure, as written, is the greenest using the rubrics below, Table 3. The rubric for the sodium dichromate procedure has been completed to act as a guide. Remember: The overall “score” for a given category is determined by the lowest green-index-value for that category. active manganese dioxide on silica Oxidant/Reactants Solvent reaction isolation purification Energy reaction isolation purification Purification Method

Details

Score

Total Score

/20 /20 /20 /20 /5 /5 /5 /5 /100

Step 4: Assessing the efficiency of Oxidation reactions using green metrics Green metrics provide a tool to compare the theoretical reaction efficiency (percent atom economy), amount of waste generated (E Factor), and reaction efficiency with relative hazards of the waste stream (effective mass yield) of all potential procedures. 1a. Write a balanced equation for the reaction before your modifications.

1b.Write a balanced equation for the reaction you performed.

2. Calculate the atom economy for the reaction before your modifications and for your reaction. How do they compare?

# MW & # & MWCamphor products % ( )100 = % (( % MW % " MW ( borneol + MW MnO2 ' $ reagents ' $ # & 152.23 % ( )100 = 63.1% $154.25 ' for the relative toxicity as well as the reaction efficiency by focusing only on the 86.9368 3. Effective mass +yield accounts hazardous components of the waste. It uses the actual masses of reagents used and products generated in the reaction. Calculate the effective mass yield for the reaction before your modifications and for your reaction. How do they compare?

! NOTE: Calculate effective mass yield assuming 100% yield.

# & # & MassCamphor % Massproduct ( % (( )100 = % Mass ( % Mass %" C 4 H10O + MassCH 2Cl 2 ' $ nonbenign ( material ' $ # 0.152 & % ( )100 = 100% $ 0 '

48