Expt. 3: Radical-Initiated Synthesis Name(s): Matt Smith & Jackie Bedsaul Date: February 11, 2012 Introduction: NBS has been frequently used by chemists to initiate ...
Expt. 3: Radical-Initiated Synthesis Name(s): Matt Smith & Jackie Bedsaul Date: February 11, 2012 Introduction: NBS has been frequently used by chemists to initiate bromination among a variety of compounds. As seen in Rajesh’s experiment, entitled, “Bromination of Deactivated Aromatics: A Simple and Efficient Method,” deactivated aromatic compounds were monobromiated using NBS. In particular, bromobenzene was selected as an intended product of interest based on wide pharmaceutical use.
Along with NBS, smaller quantities of H2SO4 were used based on
excellent yields using NBS. 2-nitrobenzaldehyde was observed to create 4-bromo-2nitrobenzaldehyde in a regioselective bromination process. Compounds such as this are capable precursors in the synthesis of pharmaceutical ingredients including ‘Bromperidol’ and ‘Ambroxol.’ These highly deactivated aromatic compounds are chosen for the synthesis due to high yields, simple procedure, and lessened need for harsh additives when using NBS. Purpose: The purpose of this experiment is to perform a benzylic bromination using NBS and ptoluic acid. Benzoyl peroxide will be used as a radical initiator to assist in breaking apart NBS to create an initial bromine radical. Due to carcinogenic properties of carbon tetrachloride, used in previous reactions, chlorobenzene will be used instead as a safe solvent. Success will be determined by characterization of mass/melting point; percent yield of the final product, and IR interpretation to conclude the correct identity of the expected product. Reaction:
Physical Properties Substance
Structure
Molecular
MW
Formula
(g/mol)
MP (°C)
BP
Density
(°C)
(g/mL)
p-Toluic Acid C8H8O2
136.15
180-181
N/A
N/A
C4H4BrNO2
177.98
175-178
N/A
N/A
C14H10O4
242.23
103-105
N/A
N/A
C6H5Cl
112.56
N/A
131
1.11
C5H12
72.15
N/A
36
626
C8H7BrO2
215.05
223-227
N/A
N/A
N-bromosuccinimide
Benzoyl peroxide Chlorobenzene
Pentane α-Bromo-p-toluic acid References: Sigma Aldrich
K. Rajesh,M. Somasundaram,R. Saiganesh,* and, and K. K. Balasubramanian Bromination of Deactivated Aromatics: A Simple and Efficient Method The Journal of Organic Chemistry 2007 72 (15), 5867-5869 Diagrams: Use ChemDraw to build Figure 3.1: Reflux Set-up and paste here.
Experimental Procedure: 1.365 grams of p-toluic acid and 1.8001 grams of NBS were added to the 100mL RBF with stir bar.
0.2038 g benzyl bromide was added to reaction along with 15mL of
chlorobenzene. Reflux started at 6:50PM and ended at 7:20PM. Heat was reduced from 4 to 2 as reaction began to bubble violently. Yellow slurry was apparent upon entry into ice bath. After 5 minutes, slurry was broken apart and vacuum filtered with 3 5mL portions of pentane. Solid was combined with 50mL of deionized water and mixed until dissolved completely. Slurry was vacuum filtered and dried. 10mL of ethyl acetate was added to dry product in separate flask and heated until dissolved. Flask was submerged in ice for recrystallization for 10 minutes. Crystals were collected and massed along with melting point analysis. Calculations: (Try using “Equation Editor” to make this section look neat). mmols of p-toluic acid: (grams of p-toluic acid x 1/MW of p-toluic acid x conversion factor)
mmol of N-bromosuccinimide: (grams of N-bromosuccinimide x 1/MW of N-bromosuccinimide x conversion factor)
mmol of benzoyl peroxide: Used in a catalytic amount Limiting Reagent: p-toluic acid Theoretical Yield of α -Bromo-p-toluic acid (mmols of LR x MW of product x conversion factor = theoretical grams of product)
Percent Yield for α -Bromo-p-toluic acid: Percent Yield =
Actual Yield Theoretical Yield
x 100%
Data: 1. Lab Partner’s Name Jackie Bedsaul 2. Mass of product 0.6649g 3. Appearance of product pale, yellow powder 4. Melting point of product 162 degrees Celsius Conclusion: Overall, this experiment achieved the intended reaction, although not at the intended yield. The obtained mass of the final product measured in at 0.6649 grams, equaling out to 30.39% yield. Low percent yield may be due to measurement errors of the actual NBS into the reaction. Lower amounts of Bromine availability may cause lowered yields. Also, this may be caused by the simple explanation of the regioselectivity of the bromination placement onto the primary carbon. Other products may have been formed in other yields. Appearance was as expected, showing a pale, yellow color, indicating the initiation of the reaction. However, the melting point remained much lower than expected at 162 degrees Celsius. Around 60 degrees away from the normal temperature range, the product may have been contaminated with excess starting material, lowering the melting point. For success in the future, more accurate amounts of each reagent should be identified and used in the reaction. The total time of reflux should span over another 30 minutes over lower heat, to ensure the reaction takes place in good yield.
