Indian Journal of Chemistry Vol. 50A, June 2011, pp. 788-792
Notes Eutectic mixture-directed kinetics of Diels-Alder reaction Amit S Nagare & Anil Kumar* Physical Chemistry Division, National Chemical Laboratory, Pune 411 008, India Email:
[email protected] Received 29 April 2011; revised and accepted 18 May 2011 In the search for environmentally benign solvent media, a new class of solvents composed of mixtures of carbohydrates with urea or methylated urea has been noted to be effective in enhancing the reaction rates of a bimolecular organic reaction like the Diels-Alder reaction of cyclopentadiene with methyl acrylate. The viscosity of these media appears to be an important parameter in controlling the second order kinetics. Keywords: Cycloaddition, Diels-Alder reaction, Solvent effects, Kinetics, Reaction rates, Viscosity, Carbohydrates, Urea, Dimethylurea
Kinetics of a bimolecular organic reaction like DielsAlder reaction is generally not affected in conventional organic solvents due to the presence of an isopolar activated complex.1 However, due to environment pollution caused by the use of volatile organic solvents or compounds, there is a constant search for alternate solvents and techniques to carry out these reactions in environmentally benign conditions. In an interesting discovery, water proved to be an important solvent to enhance the reaction rates and stereoselectivity of Diels-Alder reaction.2,3 It was Rideout and Breslow,4 who showed that a simple Diels-Alder reaction was several times faster in water than in a non-polar solvent like 2,2,4-triethylpentane. After Breslow’s pioneering work on accelerating Diels-Alder reactions in water, an upsurge in research activities related to bondmaking bimolecular reactions in water and its solutions with salts has been witnessed. The rate enhancement of such reactions in water and aqueous salt solutions has been ascribed to polarity,5-11 hydrophobic packing12,13, hydrogen bond, hydrophobic hydration14,15 and Lewis acid catalysis.16,17 Of these, the hydrophobic packing of substrates in aqueous environment has led to the enhanced reaction rates, yields and stereoselectivity values.
Salts like LiCl, NaCl, CaCl2, etc., that increase the rates of the reactions are called salting-out agents, while those like guanidinium chloride, LiClO4, etc., which inhibit the reaction rates are called salting-in agents. Breslow and Connors18 have noted that the salts which increase the reaction rates can be called as prohydrophobic and the rate inhibiting salts as antihydrophobic. It has further been noted by Breslow and Guo19 that salts influence the rates of these reactions when their solutions are prepared in “water-like” high structured solvents like ethylene glycol, formamide, etc. It has also been possible to use an appropriate combination of these compounds for this purpose. The carbohydrate-urea mixtures used as novel alternative solvents are recyclable and environment-friendly and can help in improving the performance of organic reaction processes, both economically as well as ecologically.20 In this work, an effort has been made to quantify the physical-organic aspects in terms of kinetic parameters of a simple Diels-Alder reaction in the mixtures of urea or its derivatives with carbohydrates. Also, the utility of this special class of compounds, which is often a mixture of carbohydrate with another organic compound, for Diels-Alder reaction has been explored. Experimental Maltose, mannitol, citric acid and fructose of AR grade were purchased from Thomas Baker (Mumbai, India). Cyclopentadiene, dextrose (anhydrous), calcium chloride and urea of GR grade were used as obtained from Merck. Ammonium chloride (lab. grade) was purchased from Loba Chemie. N, N′-dimethylurea (DMU) and methyl acrylate were purchased from Spectrochem. An initial screening was carried out to identify stable and low melting mixtures of bulk carbohydrates, urea and inorganic salts. Table 1 summarizes the most suitable melts in terms of stability and melting temperature. Thermal stability of the melts (all mixtures) was analyzed by differential scanning calorimetry, through three heating-cooling cycles, which showed no thermal decay. In addition, the mixtures were heated for 4 h to 95 °C without any evident decomposition.
NOTES
Table 1 − Stable melts of carbohydrates, urea and inorganic salts M. pt. (K) 353.15 363.15 363.15 358.15 348.15
Carbohydrate
Ureaa
Salt
Fructose Maltose Dextrose Mannitol Citric acid
DMU DMU Urea DMU DMU
NH4Cl NH4Cl -
a
DMU = N, N′-dimethylurea
Viscosity measurements were made on a Brookfield Ultra-Rheometer (LV III). The viscosities were obtained using the equation, η = (100/RPM) × TK × Torque × SMC, where RPM, TK (0.09373) and SMC (0.327) are the speed, viscometer torque constant and spindle multiplier constant, respectively. Calibration of the instrument was carried out against the viscosity data of water and aqueous CaCl2 solutions. Temperature of the solution was maintained to within ± 0.01 K using a Julabo constant temperature thermostat bath. The viscosities were measured with an accuracy of 1 %. Each measurement reported here is an average of triplicate reading with a precision of 0.3 %. In a standard kinetic run, 1 mL of the dienophile was added to 10 mL melt of fructose and DMU, and the reaction mixture was allowed to equilibrate at the desired temperature. The reaction was initiated by addition of the diene (1 mol in 10 mL). Progress of the reaction was monitored at appropriate time intervals by extraction of aliquots with ether followed by appropriate dilution and GC analysis on a Varian CP-3800 gas chromatograph. The reaction mixture was magnetically stirred for about 5 h. The process of severance of product was carried out by extraction, in which hot water was added to the reaction mixture and the product was extracted from aqueous phase with pet. ether. The crude product obtained in this sequence was run through the column of Silica of mesh 80-90 size with elute of 3 % of ethyl acetate and pet. ether. The GC configuration consisted of CPSIL 5CB column of length 15 m and diameter 0.25 mm with a flow rate of 0.8 mL/min of nitrogen. The injector and the detector temperatures were maintained at 200 °C and 250 °C, respectively. The total run time was 20.56 min with chlorobenzene as the internal standard. The GC method was calibrated with respect to the product concentration; the amount of product formed as a function of time gave the extent of the reaction. A plot of x/a(x-a) against time t, where a and x are the initial concentration of
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reactants and the concentration at time interval t, respectively offered a linear relationship. The rate constants thus determined were accurate to within 6 %. The precision of the rate constants as determined from an average of triplicate measurements under identical conditions was better than 3 %. The endo- and exo- stereoselectivities were analyzed using 1 H NMR spectroscopy with an accuracy of 5 %. Results and discussion The melting points of fructose and N, N′-dimethylurea (DMU) are 103 °C and 180 °C, respectively. On heating the mixtures of fructose and DMU with a definite composition, the fructose-DMU mixture offers a clear viscous melt at 80 °C, while for mannitol, addition of NH4Cl was necessary to achieve such a low melting temperature. In the case of the fructose-DMU (40:60) mixture, a blend of 0.12 mol of DMU and 0.03 mol of fructose led to a stable melt at 80 °C. Diels-Alder reaction of cyclopentadiene with methyl acrylate (Scheme 1) was carried out in the carbohydrate-urea mixtures as solvent in this reaction. The kinetic results of the studied Diels-Alder reaction are reported in Table 2. The reaction was carried out in the solutions of carbohydrates and DMU to yield a value of k2 as 23.6 × 10-5 M-1s-1. As seen from results in Table 2, mixture of citric acid with DMU is not an effective solvent medium to carry out this reaction as the reaction becomes very slow with poor yield.
Scheme 1
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Table 2 − Kinetic and viscosity data for the Diels-Alder reaction of cyclopentadiene with methyl acrylate in carbohydrate-ureasalt eutectic melts Comp. of melt Fructose/DMU (40:60) Dextrose/urea (50:50) Citric acid/DMU (40:60) Maltose/ DMU/NH4Cl (60:40:10) Mannitol/ DMU/NH4Cl (50:50:10) a
React. temp. (K)
105k2 (M-1s-1)
Yielda (%)
η (mPa S)
353.15
23.6
65
35.3
358.15
4.04
65
24.9
348.15
3.17
-
289.6
363.15
0.335
79
1732.7
363.15
1.43
74
-
Isolated yields after extraction.
While the mixture of dextrose with urea offered 65 % yield, the reaction did not proceed well in this mixture either. The reaction was noted to be nearly twice as fast in the mixture of 60 % DMU with fructose as compared to its 49 % mixture with fructose. Similar increase in the rate constants has been observed while moving from urea/DMU-poor mixtures to its rich mixtures. This effect is demonstrated in Fig. 1, in which the second order rate constant k2 are plotted against percentage of urea or DMU in the of carbohydrateurea melts. These data demonstrate that the value of k2 is strongly dependent on the percentage composition of urea in the solvent media. Further, the reaction was also carried out in ternary mixtures of DMU-NH4Cl with maltose or mannitol. The reaction was again noted to be slow but the products were in comparably high amounts. Mannitol/DMU/NH4Cl (50:50:10) yields 74 % product at 90 °C with k2 as 1.43 × 10-5 M-1s-1, while solvent mixture like dextrose/urea (50:50) at 85 °C gives 65 % of the product. On the other hand, citric acid/DMU (40:60) gives the melt at 75 °C with the product in traces with k2 = 3.17 × 10-5 M-1s-1. An array of data on k2 of the reaction in different solvent media of eutectic type having different compositions of urea is given in Table 3. The melting points of the different solvents mixtures are different for the formation of a stable melt (fructose/DMU: 80 °C; maltose/DMU/NH4Cl: 90 °C; mannitol/DMU/NH4Cl: 90 °C, glucose/urea: 85 °C; citric acid/DMU: 75 °C). As the percentage composition of DMU in fructose/DMU melt increases,
Fig. 1 − The plot of k2 versus composition of binary mixtures of carbohydrate-urea for Diels-Alder reaction. [(a) fructose/DMU; (b) dextrose/urea; (c) maltose/DMU/NH4Cl (○), mannitol/DMU/NH4Cl (∆), citric acid/DMU (□)].
NOTES
the k2 value also increases from 13.68 × 10-5 M-1s-1 to 23.59 × 10-5 M-1s-1.The value of k2 increases from 1.89 × 10-5 to 3.17 × 10-5 M-1s-1 in the citric acid-DMU mixture. The glucose/urea melt offers an array of second order rate constant from k2 = 1.34 × 10-5 M-1s-1 to 4.04 × 10-5 M-1s-1. About 8-fold increase in rates is observed in the Table 3 − Second order rate constants (k2) for Diels-Alder reaction of cyclopentadiene with methyl acrylate in carbohydrate-urea-salt melts DMUa or urea (%)
105k2 (M-1s-1)
η (mPa S)
Fructose/DMU at 353.15 K 40 45 50 60
13.68 20.94 22.09 23.59
318.4 195.3 134.5 35.3
Citric acid/DMU at 348.15 K 40 50 55 60
1.89 2.75 3.04 3.17
2863 990 584 289.6
Dextrose/Urea at 358.15 K 30 40 45 50
1.34 2.83 3.14 4.04
461.3 101.2 60.5 24.9
Maltose/DMU/NH4Cl at 363.15 K 40 0.33 50 1.68 60 2.38 70 2.62
1732.7 313.4 187.4 80.9
Mannitol/DMU/NH4Cl at 363.15 K 40 0.29 45 0.33 50 1.43 60 3.06
-
a
DMU = N,N′-dimethylurea
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maltose/DMU/NH4Cl melt while in mannitol/DMU/NH4Cl, it is about 21-times. Since these solvent media are composed of two or more solutes and are clearly melts, the rates of the reaction are expected to depend upon the viscosities of the media. While the role of viscosity on the kinetics of organic reactions has been a subject of controversy, studies from this laboratory have confirmed that the viscosity of organic solvents has a profound influence on the rates of Diels-Alder reactions.21,22 Initially, the k2 values increase with increase in viscosity up to 1 cP and then decrease with viscosity above 1 cP. The increase in rate up to the 1 cP range is ascribed to the vibrational activation theory, according to which an increase in viscosity facilitates the bond making phenomenon. In this region, the vibrational modes are enhanced at the expense of the translational modes. However, the rates are lowered in solvents possessing high viscosities. Since the reactants cannot “see each other” in such a highly dense and viscous environment, the rates decrease in such a region. From the viscosity data given in Table 3, it is observed that the viscosity of the respective melt decreases with a decrease in the percentage of urea or DMU. These results show that viscosity plays a significant role in determining the rate of the reaction. This observation is shown in Fig. 2, in which the ln k2 values are plotted against η for the citric acid-DMU and glucose-urea mixtures, showing a strong correlation between ln k2 and η. Temperature dependant kinetics of Diels-Alder reaction was also investigated. An Arrhenius plot for the reaction in citric acid-DMU for the ratio (40:60) at varying temperatures (Fig. 3) gives a value of activation energy as 108.28 kJ mol-1.
Fig. 2 − Representative plots for ln k2 versus η for Diels-Alder reaction in (a) citric acid-DMU and (b) glucose-urea mixtures.
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solvent molecules. Carbohydrate-urea melts are highly ordered reaction media and the activation energies for reactions carried out in these melts can be high because it is necessary to break the order of the medium to bring together all the components to the reaction site. Therefore, the rate constants are better correlated with solvent viscosity. In summary, in the present study we have attempted to demonstrate that the eutectic mixtures consisting of carbohydrate and urea can be potential solvent media to accelerate a bimolecular organic reaction.
Fig. 3 − The plot of ln k2 versus 1000/T for citric acid-DMU mixture (40:60).
The role of polarity of these highly viscous solvents needs to be emphasized. In perspective of the reaction studied herein, the carbohydrate-urea melts used as media possess very high viscosity when compared with that of water, which will decrease with increasing percentage of urea in the melt. In the present solvent media the viscosity decreases with increasing rate of reaction (Table 3). In other words, we can say that the order of magnitude of the diffusion coefficients contrasts with the viscosity of the solvent melt. The relationship between the self-diffusion coefficient and viscosity was analyzed in terms of Stokes–Einstein equation, D = kT/6πrη, where k = Boltzmann constant (1.38 × 10-23 J/K), η = solvent viscosity (cP), T = temperature in K, r = radius of solute molecule related to molecular weight. From the data given in Table 3 we observe that the experimental rate constants for the carbohydrate melt used for Diels-Alder reaction are low when the percentage of urea in melt is low. This suggests that the carbohydrate-urea melts employed herein do not behave as highly polar solvents. Therefore, on the basis of the above results, we suggest that polarity is not the sole parameter that determines the solvent effect on rate constant in Diels-Alder reaction since the reaction requires separation and reassembly of
Acknowledgement This research is supported by a J C Bose National Fellowship awarded to one of us (AK). References 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
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