MICROWAVES IN ORGANIC AND ORGANOMETALLIC SYNTHESIS R. Gedye, F. Smith, and K. Westaway This study shows that chemical reactions in polar solvents can be carried out rapidly and conveniently using microwave heating in sealed Teflon containers, Reactions of organic and organometallic compounds are reported, and rate enhancements of up to 1,240 times have been observed. The acceleration of reactions (compared to normal reflux conditions) occurs because the increased pressure developed inthereaction vessels causes superheating of the solvent. The rate of absorption of microwave radiation is affected by the Polarity and the volume of the reaction mixture. The heating rate is also influenced by the presence of ions in solution. The yields of relatively slow reactions can be increased byprogramming the power levels of the microwaveoven. This technique allows the reactions to be carried out more safely andto be scaled up to.some extent. Microwave heating results in considerable energy savings compared with conventional heating methods. The energy efficiency can be further increased by power programming. Microwave heating has not been found to alter the composition of products of a chemical reaction appreciably. While small differences in product ratios are observed in reactions carried out under microwave and conventional heating, this appears to be merely athermal effect and can be atiributed to the higher temperatures achieved in microwave reactions. Key Words: Microwave, Synthesis, Organic, Organometallic, Rate en- hancement. ABOUT THE AUTHORS: RIN. Gedye, F.E. Smith, and K.C. Westaway are affiliated with Laurentian University, Ramsey Lake Road, Sudbury, Ontario, Canada P3E 2C6. © Intemational Microwave Power Institute 1991 International Microwave Power Institute T he use of microwave ovens for the rapid synthesis of | ‘organic compounds was first reported by Gedye et al. [1986]. It was observed in our laboratories that organic reactions were dramatically accelerated by irradiating the reaction miature in sealed Teflon containers with microwaves, Thiscouldbe exploited in the rapid synthesis ofa wide variety of compounds. Some examples of these reactions included the hydrolysis of amides and esters to carboxylic acids, the esterification of carboxylic acids with alcohols, and the conversion of alkyl halides to ethers [Gedye et al.,1986]. Shortly after our initial communication, Giguere etal. [1986], reported substantial reductions in reaction times in syntheses using the Diels-Alder, Claisen and ene reactions using a microwave oven. ‘This rapid and convenient method has since attracted a _greatdeal of attention and anumber of synthetic andanalytical applications of microwave heating of organic reactions have been reported during the last unree years [Agod et a., 1989; Alloum etal., 1989; Chiou, 1989; Gedye, etal., 1988a; Gedye, etal., 1988b; Giguere et al., 1987; Gutierrez, et al., 1989; Jie and Yankit, 1988; Linders et al., 1988; Straathofetal., 1988; Stroop and Schaefer, 1989; Takanoetal., 1989; Yuetal., 1988}. ‘The field has recently been reviewed by Giguere [1989]. ‘This paper describes our research on the application of this new microwave technique to the synthesis of organic and ‘organometallic compounds, and includes astudy ofthe factors which affect the rate increases in these reactions. In addition, our attempts at scaling-up and reducing the energy requirements of these syntheses are presented, Experimental Apparatus Unless otherwise stated, the reactions were carried outin 150 ml PFA Teflon containers manufactured by the Savillex Corporation (Minnetonka, Minnesota, USA]. A domestic Toshiba model ER-8000 BTC microwave oven with9 power settings, starting at 72 watts and increasing by 81 watt increments to 720 watts, was used to provide the energy. ‘The output power of the oven at power setting 9 was ‘measured using the IEC 705 (1988, 2nd edition) power rating test, and was found to be 698 watts,General Procedure i) Microwavereactions- the reaction mixture wasplaced ina 150 ml Savillex Teflon vessel and the lid screwed on tightly. The sealed vessel was then placed in the. microwave oven and heated at the appropriate power level for the specified time. Afterallowing to stand for 2minutes to reduce the pressure, the vessel, which was stil! hot, was removed from the oven andcooledin ice- water for 5 minutes before the top was unscrewed. ii) Conventional reactions - the reaction mixture was refluxed under atmospheric pressure for the specified time (measured from the time boiling commenced). Reaction products for both types of reaction were iden- tified by their melting or boiling points and by nmr and ir spectroscopy. Pressure and Temperature Measurements Pressure measurements were carried out by connecting the cap of a 150 ml Savillex bottle to a pressure gauge outside the microwave oven. The bottle was connected to the pressure gauge by a 1/4 in, to 1/8 in. Swagelok reducing adapter, a 1/8 in, Teflon tube that passed through a small hole drilled inthe back of the oven, and a Swagelok fitting. The pressure was recorded at regular intervals (usually every 30 sec.) for the duration of the heating period. The final temperature in the sealed vessel was estimated by pointinga Williamson 600 infrared sensor atthe mixture in the vessel immediately after the heating was completed, The temperature readings from the sensor were in good agreement with those predicted from the pressure in the Teflon bottles (Foust et al., 1980). Safety Precautions Increasing the volume of the reaction mixture can cause an increase in pressure and temperature which can lead to deformation ofthe Teflon vessel. Toensureasafeexperiment, the solvent volume should not exceed 10% of the volume of the container, When volatile solvents are used, power levels of greater than 560 watts should be avoided, except for very short periods of time, Alternatively, the pressure can be ‘monitored and the power level reduced tomaintain the pressure atasafe value, Savillex vessels containing pressure releasing caps (designedto ventat 100 psi) can also be used. Theboiling of flammable solvents in open vessels is not recommended, Experiments in microwave ovens should be carried out in a fume hood. 4 Journal of Microwave Power and Electromagnetic Energy Programming Thistechnique involves heating the reaction mixture at power evel 9 (720 watts) until the pressure in the vessel reaches 60 psi. For the remainder of the reaction time, the pressure is ‘kept constant (between 55-65 psi) by reducing the powerlevel to 1-3 (depending on the volatility of the solvent) or by irradiating the reaction mixture for shortintervals.t’720 watts Rate Enhancements ‘The rate enhancement for comparable microwave and con- ventionally heated (reflux) reactions, using identical con- centrations of reactants, were calculated in the following manner: Rate enhancement = (Reflux time / Microwave time) where the reflux time and the microwave time are the times equiredtotakeareactiontothe same state of completion under reflux conditions and in the microwave oven, respectively. ‘The reflux times quoted do not include the time taken for the solvent to reach the boiling point. Energy Savings ‘The percent energy saving for a microwave reaction over an identical reflux reaction was calculated using the formula Es = 100(1-[EM/ERI) where Eg is the percent energy saving, EM is the energy required for the microwave reaction, and ER is the energy required for the reflux reaction, Results and Discussion ‘Anumber of differenttypes of organic reactions were carried out both in sealed Teflon containers in microwave ovens and under conventional reflux conditions. Substantial reductions in reaction times were observed in the microwave reactions and rate enhancements, varying from 6 times in the hy- drolysis of benzamide to 240 times in the Sy2 reaction of 4-cyanophenoxide ion with benzyl chloride in methanol, were achieved using the normal technique. A rate en- hancement of 1200 times was achieved when the latter re- action was carried out in a 50ml Teflon bomb [Gedye, etal., 1986, 1988a].. The results of some representative reactions are shown in Table 1. Vol. 26 No. 1, 1991TABLE 1 Reaction times and yields in representative syntheses using microwave and reflux techniques. Compound Procedure Reaction Average Solvent Rate synthesised followed time yield(%) enhancement (CeHHs)3SnCi Microwave 7 min 81 none 26 (CeHs)3SnC1 Reflux 3h 82 (Colis)3$n08 Microwave 4 min 0 CoHsOH 15 (C6Hs)3Sn0H Reflux thr 6 Hydrolysis of benzamide C6HsCOOH Microwave 10 min 99 #0 6 CoHisCOOH Reflux Lhe 90 Hydrolysis of methyl benzoate C6HsCOOH Microwave 2.5 min 8 20 4 CeHsCOOH Reflux The 95 Esterification of benzoic acid with methanol CoHisCOOCH3 Microwave S min 16 (CHO 96 CeHsCOOCH3 Reflux She 4 Conversion of benzophenone to oxime (Cotls)2C:NOH Microwave 2min n CoHsOH 60 (CoHls)2C:NOH Reflux 2he 68 pyridine ‘Sy2 reaction of 4-cyanophenoxide ion with benzyl chloride NCCéHsOCH2CéHs Microwave 4 min 89 HOH 240 NCCgHsOCH2CgUs Reflux 16 he 8 Forsafety reasons, themicrowave method wasonlyused Effect of the Solvent for preparing relatively small amounts (up to 2-3 grams) of products, since our early attempts at using larger reaction volumes resulted in very high pressures being produced. On one occasion, a violent explosion occurred when ap- proximately 40 ml of a mixture containing toluene, KMnO4, and aqueous KOH was heated in a 50 ml Teflon bomb, Microwave heating was found to be particularly useful for preparing derivatives for the identification of organic ‘compounds [Gedye etal, 1988b] where only small amounts, of products are required, For example, oximes of aldehydes and ketones could be prepared in good yieldin only 2 minutes, compared witha reflux time of 2 hours (Shriner etal, 1980} Once ithad been shown that microwave heating could be useful in the rapid synthesis of a wide range of compounds, attention was turned to a study of the factors which affected the rates of the reactions as well as the safety of the method. International Microwave Power Institute ‘An important factor that affects the rate of a reaction carried out in a microwave oven is the polarity of the solvent. It has been known for some time that polar molecules absorb microwaves, resulting in increased rotation. This causes heating of the substance through frictional effects [Copson, 1975; Watkins, 1983)._ It would follow that the rate at which a solvent absorbs microwave irradiation depends on its polarity, i.. its dielectric constant. An experiment was performed to determine the increase in temperature when equal amounts (0.5 mol) of a number of liquids were heated for 15 seconds in the microwave oven. twas found that strongly polar compounds suchas water, alcohols, and ketones heated up most rapidly, whereas less polar liquids, e.g. ethers, amines, and alkyl halides showed smaller temperature increases. Asexpected, little orno heatingoccurred with nonpolar liquids, e.g. carbon tetrachloride and hydrocarbons. ‘The data in Table 2 and Figure 1 show that temperature increase isrelated tothe dielectricconstant ofthe liquid, since 11 outof 13 polar organic liquids are close to the best straight line through the temperature increase vs. dielectric constant plot. ‘Thus, microwave heating should produce the most dra- ‘matic rate increases in solvents of high dielectric constant. ‘Theresults in Table 1 show thatthe greatestrate enhancements were obtained for reactions in methanol. Reactions in water and higher boiling alcohols, on the other hand, showed smaller rate increases. Since the shorterchain alcohols produce more water (on a weight basis) during the esterification, some of the rate enhancements noted in these instances may be due to microwave absorption by this extra water. The results in Table 3 show that in the esterification of benzoic acid, the rate enhancement is greatest for methanol and decreases as the chain length of the alcohol increases. The dielectric constants of alcohols decrease only ‘gradually asthe chain length increases. Thus, the heating rates for all these alcohols in the microwave oven are similar. A ‘more important factor affecting the rate enhancements is that the rate of the reflux reaction increases with the boiling point ofthealcohol. These resultsmightsuggestthat the microwave technique produces significantrateincreasesonly in reactions TABLE 2 ‘The increase in temperature found when 0.5 mol of liquids are heated for 15 sec. at 560 watts in an open vessel in a microwave oven. ‘Compound ‘Temp. increase after 15 sec. 1,4-dioxane u ‘Tripropylamine 10 Propanoic acid 19 Chloroform Py n-propyl acetate 28 Ethyl acetate 29 Acetic acid 38 | -Hexanol 45 1 -Pentanol 31 2-Pentanone 49 1-Butanol 56 2-Butanone 4 1-Propanol o Methanol . Ethanol . Water 44 * liquid boiled before 15 seconds had elapsed 6 Journal of Microwave Power and Electromagnetic Energy Boiling point Dielectric ic} constant 101 22 156 24 141 33 oe 48 102 56 n 60 18 62 158 138 137 139 102 154 7 178 80 18.5 7 20.1 4 326 B 243 100 785 Vol. 26 No. 1, 1991in low boiling solvents, However, the rate of reactions in higher boiling solvents can be increased significantly by using a higher power level in the microwave oven. For example, the rate enhancement for the esterification of benzoic acid with 1-pentanol was increased from 1.3 10 6.1 by a small increase in power from 560 watts to 630 watts, Effect of Pressure In our earlier experiments it was observed that very high pressures were generated in microwave-heated reactions if low-boiling solvents, such as methanol, were used. In some of these reactions, deformations of the Teflon Duar sca containersorevenexplosions occurred. The increased rates ofreactionarebelieved tobe the result of rapid superheating FIGURE 1: Effect of dielectric constant on of the solvent. This leads to the substantial increase in the heating rate of various organic liquids. pressure that is observed. Since the effect of pressure TABLE 3 Reaction times and rate enhancements for the esterification of benzoic acid with different alcohols under conventional and microwave heating Alcohol Approx. Reaction % yield Rate reaction time Enhance- temp. °C ‘ment Methanol 65 8 hr (reflux) 4 134 5 min (M-wave) 16 96 1-Propanol 7 4 hr (reflux) B 135 6 min (M-wave) ” 40 1-Butanol 7 The (reflux) 82 135 7.5 min (M-Wave) 9 8 1-Pentanol 137 10 min (reflux) 83 137 7.5 min (M-wave) 9 13 1-Pentanol at 630 watts 162 1.5 min (M-wave) 1 61 9 Allreactions were done using 10 ml of the alcohol in a 300 ml Berghof bottle. A ten-fold molar excess of the alcohol to benzoic acid was used. With the exception of the I-pentanol reaction at 630 watts, all the reactions were carried out at 560 watts International Microwave Power Institute 7appeared to play a significant role in the rate enhancements, the effect of pressure on the rate of the Syy2 reaction of 4- cyanophenoxide ion with benzyl chloride in methanol was investigated. ‘The rate enhancements of this reaction when identical amounts of reagents were reacted 065% completion in 50 ml, 120ml, and 300 mi Teflon vessels were determined. ‘The results in Table 4 show that the rate of reaction increased markedly when the volume of the Teflon container was reduced. A plotof I/volume of the vessel vs. I/reaction time, Figure2, waslinearand thus the rate of reaction variesinversely with the volume of the vessel. Hence, the rate of reaction is, proportional to the pressure developed. Initially, the microwave energy is used to bring the reaction mixture to a boil. If one assumes that all of the microwave energy added othe ovenisabsorbedby thereaction ‘mixture, extra energy will presumably be used to convert Ln solvent molecules to the vapor state and the pressure inside the vessel will increase. If a smaller vessel is used, higher pressures will result. Since the boiling point ofthe solvent is higher at higher pressures, the reaction occurs at a higher temperature, and therefore faster, in smallerreaction vessels. Pressure Measurements, Power Levels ‘The above observations demonstrated that the rate en hhancements were theresult ofa pressure increase in the action vessel. Thepressure, and hence the lemperature, inthe reaction vessel dependson theamount of microwave energyabsorbed. For this reason, as well as for safety considerations, it was considered important to determine the factors that affected the absorption of microwave energy by organic compounds in Teflon containers. The first experiment was done to determine the effect of the power level on the amount of microwave radiation that is absorbed by a fixed amount of liquidin the Teflon containers. Asexpected, theresults, shown in Figure 3, indicate that the pressure increases more rapidly ‘when the power level is higher. Thenextsetofexperimentsinvolved examining theeffect, of the volume of the solvent on the heating rate. Different ‘volumes ofsolvents wereheated at 560 watts in he same Teflon vessel and the pressures determined at various times. "The results are shown in Figures 4-6. When the volume of the oa ess 3.8 solvent is small, the pressure increases as the volume of the 2/vol of container (1) solvent increases. However, as the volume of the solvent increases, a point is reached where a larger volume of the solvent is not heated more quickly. In fact, this pattern was FIGURE 2: Effect of volume of con- found withall the solvents tested. [tis worth noting, however, tainer on the rate of an Sy2 reaction. that the final pressure reached with the larger volumes of TABLE 4 Time required to obtain 65% yield of benzyl-4-cyanophenyl ether using equal amounts of sodium 4-cyanophenoxide, benyl chloride and methanol in vessels of different sizes. Volume of Time for the Teflon 65% vessel (ml) reaction 30 35 secs 120 13 min 300 3.0 min Journal of Microwave Power and Electromagnetic Energy 1Wolume 1/time Rate (liter) (/min) enhancement 20.0 im 1240 83 0.75 540 33 033 240 Vol. 26 No. 1, 1991FIGURE: Effectofpower setting on the microwave heating of I-propanol. FIGURE 4: Effect of he volume of water ina sealed 150 ml Savillex bottle on heating rate. solvent is atleast as high as that found with smaller amounts of solvent, asshown in Figure 5. This probably occurs because ittakes longer to heat the larger volume of solvent tothe same. temperature at the same power level. The volume of solvent which heats most rapidly is different for different solvents. For example, the most rapid pressure (temperature) increase is found with 15 ml of water, 20 ml of 1-propanol, and 30 ml of both 1- and 2-butanol ina 150 ml Savillex bottle. Thus, it would be expected that the greatest rate enhancements in microwave reactions would International Microwave Power Institute FIGURE 5: Effect of volume of !-propanol in asealed 150 ml Savillex bottle on heating rate. FIGURE 6: Effect of volume of 1-butanol in a sealed 150 ml Savillex bottle on heating rate. occur using these volumes of solvent. However, itwas found later (vide infra) thatthe volume of reaction mixture that heats the fastest isalsoaffected by the presence of other substances in the reaction mixture, such as ion-producing compounds. ‘The volume for which the maximum heating rate is observed seems to depend on the molecular weight and the heat capacity of the solvent. In water, the greatest increase in pressure occurs at 15 ml (0.83 mol) and a smaller rate of increase occurs at 20 ml (1.11 mol) (see Figure 4). Because 15 ml of 1-propanol and the butanols are only 0.20 mol and0.16 mol, respectively, the greatest heating rate occurs with larger volumes of these solvents. In fact, the most rapid increase in pressure for 1-propanol and the butanols occurs at 20 ml (0.27 mol) and 30 ml (0.32 mol), respectively. The ‘maximum heating rate for 1-butanol, for example, occurs at only 0.32mol rather than the0.83 mol found for water because the heat capacity of 1-butanol is approximately twice that of ‘water. Thus the amount of energy which is required to heat 15 mlof water and 30 ml of 1-butanol is almost identical and, hence, these volumes have the maximum heating rates. Optimization of Conditions ‘The information collected was used to try to increase the rate enhancement observed in the esterification of benzoic acid with l-propanol. The results in Table 5 show that the rate enhancement was increased from 18 to 60 when the volume of the reaction mixture and that of the Teflon vessel was changed to maximize the heating rate. Increasing the power level from 560 watts to 630 watts further increased the rate enhancement to 180. Thus, the rate of this reaction can be increased 10 times by optimizing the conditions. Power Programming and Scaling Up Initial attempts to scale-up the reactions resulted in slower reactions. This isto be expected since the maximum heating rates for the solvents investigated varied between 15 ml and 30 mi, and a further increase in volume decreases the heating rate and hence the rate of reaction, Reaction times can, of course, be reduced by using higher power levels (greater than 560 watts), but dangerously high pressures are produced, particularly with low-boiling solvents,e.g. methanol and water (Vide supra). The high temperatures of the reaction mixtures at these high pressures soften the Teflon. ‘This can cause ‘deformation of the vessels and even explosions. ‘A useful approach to carrying out reactions on a larger scale more safely is to use programming of the power levels. Thereaction mixtures initially heated atthe maximum power level, or 720 watts, until the maximum safe pressure (lemperature) is attained. The power level is then reduced to a lower level, which will maintain the pressure close to that value, The Savillex vessels used in the present study are designedto be safe up to 100 psi, buttoeliminate the possibility of vessel deformation or explosion, a pressure of approximately 60 psi waschosen. Programmablemicrowave ‘ovens should therefore be suitable for these experiments, However, maintaining the pressureatthis safe level was found to be difficult using a set power program. It was found that the type of program required to maintain the proper pressure varied according to the volatility of the solvent. Even when the same solvent was used, the program had to be changed for different reactionsas wellas when different volumes of solvent were used in the samereaction. It was therefore necessary to ‘monitor the pressure during the reaction andto vary the power level manually to maintain the pressure at the desired (safe) value. Using this technique, reactions could be heated for ‘comparatively long periods of time (up to 40 minutes) if necessary. Programming proved useful in obtaining good yields from slow reactions. ‘These reactions normally could not be driven to completion in a one-stage heating process at constant power level of 560 watts since excessive pressures ‘would build up. ‘A number of experiments were carried out in order to selectstow reactions where the programming technique would be useful in driving thereaction tocompletion. Thereactions selected for this study, shown below, included the acid- catalysed hydrolysis of N-phenylbenzamide (1), the esterification of benzoic acid with 2-butanol (2), and the solvolysis of benzyl chloride with water (3). The acid-catalyzed hydrolysis of N-phenylbenzamide was carried out by heating the mixture at power level 9 (720 waits) until the pressure reached 60 psi and then keeping the pressure constant by reducing the power level. Using programming, good yields of products were obtained. In addition, rate enhancements of 50-100 times were obtained even when larger volumes of solventare used (vide infra). The results are summarized in Table 6, HySO4 CoHsCONHCgHs + HO > CHsCOOH + CgHsNHp @ HyS04 C6HsCOOH + CH3CHCH,CH3, —> CeHsCOOCHCHCHs +H)0 @ oH CHy C6HsCH Cl + Hy0. > (C6HsCH20H + HCL @) 10 Journal of Microwave Power and Electromagnetic Energy Vol. 26 No. 1, 1991Another concern was that only small volumes had been used in the syntheses investigated previously. Although it proved possible to scale up the reaction, the results in Table 6 show that the rate enhancement decreases as the reaction is scaled up or if the volume of the solvent is increased. ‘The acid-catalysed esterification of benzoic acid with alcoholsusing microwave heating at 560 wattshad previously been shown to give cate enhancements decreasing with increasing chain length of the alcohol. In fact, the rate enhancement decreased from 96 for the reaction with methanol to 1.3 with 1-pemtanol (Table 3). It was found that the esterifications with primary alcohols reached equilibrium in avery short time at power level 9 (720 watts) and were therefore unsuitable for studying the effect of programming. The reaction of the secondary alcoho! 2-butanol with benzoic acid ‘was studied since this reaction occurred more slowly than those of the primary alcohols. Although the yield of ester was only '53%after8 minutes of microwave heating using programming, it was increased to 70% after 30 minutes, as shown in Table 7, Rate enhancements of 30-40 times were achieved. In both ‘of the above reactions, the yield of products in a given time was greatest when 0 mLof the solvent wasused and decreased asthe reaction was scaled up. These results were unexpecied since ithad been shown previously (Figures4-6 )that the pure solvents, i.e. waterandalcohols, had specific volumes greater than 10 ml, whereamaximum heating rate was observed. This suggested thatthe addition of HSOq (which ispresent in both reaction mixtures) might affect their heating rates. TABLES Optimization of reaction rates in the formation of n-propyl benzoate from benzoic acid and 1-propanol. Volume Power Volume % yield Time (reflux) Rate of of — enhancement propanol (watts) vessel Time (microwave) (ml) (ml) 10 560 300 46 180/10 18 20 360 150 4 180/3, 60 20 630 150 40 180/1 180 TABLE 6 Rate enhancements for the reaction between N-phenylbenzamide and 20% H2S04, using programming in the microwave oven. Reaction Time (min) 1g amide in 12 10 ml acid 2.5 g amide in 16 25 ml acid 1g amide in 8 25 ml acid International Microwave Power Institute Seyield 4 90 52. 68. 67 4 ulTABLET Yields, rate enhancements, and energy savings for the esterification of benzoic acid with 2-butanol using programming? Volume of Heating Time 2-butanol ‘method (min) (ml) 10 microwave 8 20 microwave 8 30 microwave 8 10 microwave 30 30 microwave 30 20 reflux 285 30 reflux 285 % yield of ester Rate Enhancement 33 - 49 36 42 36 70 a - 47 44 The same concentrations of reagents were used in each reaction, the relative amounts being: 0.01 mol of benzoic acid, 0.10 mol of 2-butanol and 10 drops of cone. H2SO4. It was considered possible that the presence of ions in a solvent might affect its heating rate and might alter the relationship between the volume and maximum heating rate of the solvent. The heating rates of different volumesof various solutions containing ions were therefore investigated. The results indicated that 20% sulfuric acid in water, 10% NaOH inwater, and 10% NaClin water, all heated more rapidly when smaller volumes were heated in sealed reaction vessels in the ‘microwave oven. The effectof the volume on the heating rate of 20% H2S04 is shown in Figure 7 ‘The highest yield of product in the hydrolysis of N- phenylbenzamide in20 % sulfuricacid using different volumes of solvent was obtained when the smallest volume (10 ml) of acid was used. Thus, the rates of reaction (yields) were consistent with the heating rates of ionic solutions rather than those of the pure solvent water which had amaximum heating rate at 15 ml, Because the HySOq catalyst would form ions in the solution, itwasexpected that the esterification of benzoic acid with2-butanol should occur most rapidly (give higher yields) when the volume of the alcohol was 10 ml rather than 25 ml to 30 ml (the volume of 2-butanol which had the greatest heating rate). This, in fact, was found to be the case. However,adifferent behavior wasobserved when HySOq ‘was added to different volumes of 2-butanol, The pressures 2 Journal of Microwave Power and Electromagnetic Energy (temperatures) foundat various times when different volumes of 2-butanol were heated with and without HSO4 at 560 watts ina 150 mt Savillex vessel are shown graphically in Figures Sand9. The maximum heating ate of -butanolalone occurred ata volume of 30 ml. When 20 drops of conc. HySO4 were added to each sample, the same trend was found, except that the time required toreach 60 psi was much shorter. While the acid obviously affects the heating rate, the smallest volume of the solvent does not heat up the fastest, as was found for the reaction mixture, Once ithad been discovered that ion-forming compounds altered the heating rates of solvents, it was important to determine the heating rate of reaction mixtures which did not contain ions, i..,to determine if amaximum heating rate was atthe same volume as was observed for the pure solvent. The hydrolysis of benzyl chloride, where one ofthe reactants was water and the polar alkyl halides do not form ionsiin solution, was used for this study. ‘The hydrolysis of benzyl chloride also occurred ata rate which was appropriate for scaling up studies. Different amounts of benzyl chloride were reacted with different volumes of water (keeping the concentration of the alkyl halide constant) with programming in the microwave oven, The results in Table 8 show that for a reaction time of 5 minutes the highest yield was obtained, i, the reaction occurred the Vol. 26 No. 1, 1991FIGURE?: Heatingratesfor various volumes of 20% sulfuricacid ina 150 ml Savillex vessel «at $60 watts in a microwave oven. RESSURE (9!) 0 3 THME (oee 9 35 3eE aR aa 5a PIGURE 8: Heating ratesfor various volumes of 2-butanol ina 150 ml Savillex vessel at 560 watts ina microwave oven. omy 3 # a g FIGURE 9: Heating rates of various volumes of 2-butanol with conc. sulfuric acid in a 150 mi Savillex vessel at 560 watts in a microwave oven. fastest, when the volume of water was 15 ml. This was to be expected because the heating rate for pure water was a maximum at 15 ml. If one assumes that the reflux reaction would occurat the same rate forthe 10 mi, the 15 ml, and the 20 mi reactions, the rate enhancement for the 10 ml and the 20 ml reactions are both 12. Since a higher yield of product ‘was obtained after 5 min. in the 15 ml reaction, this reaction had the greatest rate enhancementasexpected. Thisis different from the results obtained with thereactions thatcontained ions, ‘in which the rate of reaction decreased asthereaction volume increased. Tt would appear that, for reactions which do not contain appreciable amounts of ions, the rate enhancement follows the heating rate for the pure solvent. TABLE 8 Yields and rate enhancements for the reaction of benzyl chloride with water using programming. Volume of benzyl Heating chloride/votume method of water 05 my/iomt microwave 0.5 mi/10 mi microwave 0.5 mi/10 ml reflux 0.75 my/15 mt microwave 0.75 mv/iSml microwave 1.0 mY20 mt microwave 1.0 mi20 mi microwave International Microwave Power Institute Time % yield Rate (min) enhancement 3 50 5 14 12 60 n 3 59 5 85 >i2 3 59 5 8 2Energy Savings ‘Any energy savings associated with the microwave heating of chemical reactions would be an important consideration for industrial applications. Considerable energy savings are expected over conventional heating methods because of the dramatic reduction in thereactiontimes of microwave-heated reactions, particularly when programming is used. Initial investigationsataconstant power level of S60 watts {Duhaime et al, 1987) indicated that significant amounts of the energy required for a reflux reaction could be saved by using microwave heating, ‘The effect of scaling up the reaction on the energy consumption for both microwave and conventional heating (reflux using a heating mantle) was investigated for three differentreactions (see Table9). Noions were present in the firstreaction (hydrolysis of benzylchloride). Thesecond and third reactions were done in dilute sulfuric acid solutions and therefore had ions in the reaction mixture. Each of the microwave reactions was done using programming (vide supra). Theenergy consumption has been based on theamount of product to demonstrate how the energy consumption would affect production costs. ‘When the reaction volume in the benzyl chloride hy- rolysis was increased, four trends were observed. First, the yield was initially constant, then decreased markedly when the reaction volume wasmore than 30ml. Second, theenergy uused/gram of product isolated from the reaction decreased as the volume increased for all reaction volumes up to 50 ml, ‘Thisoccurredeven though the percent yield decreased, because the weightof the product increased when the volume (amount of reactants) was increased. Third, the energy savings/gram ofproductseemedtodecrease gradually asthe reaction volume increased. Although the energy savings/gram of product was expected to increase when the energy/ gram of product decreased, this was not observed because when our reflux reactions were scaledup, thesame amountofenergy wasused. Finally, the rate enhancement decreased as the volume of the reaction mixture increased beyond 15 ml (vide supra). This presumably occurred because it takes longer to heat the larger volume to the same pressure (temperature). Itis interesting to note that the percent yield decreases, and the energy used/gram of product formed increases markedly when larger volumes are used. This presumably happens because it takes longer to heat up and maintain the large volume at the reaction temperature, ‘The same trends were confirmed by an earlier set of experiments on benzylchloride hydrolysis. The percent yield increased and then remained constants the reaction volume increased. Unfortunately, the reaction volume was not taken above 20 ml where the decrease in yield was observed in the 14 Journal of Microwave Power and Electromagnetic Energy above experiments. Also, the energy used/ gram of product formed in the reaction decreased as the reaction volume increased. Similar results were obtained in the hydrolysis of N- phenylbenzamideand inthe esterification ofbenzoic acid with 2-butanol. In both of these reactions, which had ions in the reaction solution, the percent yield decreased when the volume of the reaction mixture increased for all volumes. Theenergy used/gram of productalso decreased forall increased reaction volumes. Product Composition Tthas been reported [Giguere, 1989] thatthe use of high pres- sure in organic reactions can influence not only the rae ofthe reaction butalso the product composition. Although the same products were produced using either microwave or con- ‘ventional heating in the reactions described earlier, itis of interest to determine whether microwave heating can affect ‘the composition in reactions where more than one product is produced. ‘Two typesof reactions were selected for this study. The first was the reaction of alkoxides with alkyl halides, which can giveboth substitution and elimination products; the second was the Diels-Alder reaction in whicha mixture of endo- and exo-isomers of the adduct can be produced. ‘The results in Table 10 indicate that the product com- position isnot altered significantly when the heating method for the reactions is changed from the normal reflux to the microwave technique. While small differences in product ratios are observed in reactions carried out under microwave and conventional heating, this appears to be merely a thermal effect and can be attributed to the higher temperatures used in microwave reactions. Conclusion Chemical reactionsinpolarsolventscanbe carried outrapidly ‘and conveniently using microwave heating in sealed Teflon containers, The acceleration of reactions occurs because the increased pressure developed in the reaction vessels causes superheating of the solvent. ‘The rate of absorption of ‘microwaveradiationis affected by the polarity andthe volume of the reaction mixture, The heating rateisalso influenced by the presence of ions in solution. ‘The yields of relatively slow reactions can be increased by programming the powerlevelsof the microwaveoven. This technique allows the reactions to be carried out more safely andtobescaled uptosomeextent, Microwave heatingresults in considerable energy savings compared with conventional Vol. 26 No. 1, 1991TABLE 9 ‘The reaction times, yields, energy savings, and rate enhancements for different microwave reactions with programming. Wat(g) reactant Reaction Energy (J) energy Rate Time (sec) Time yield used savings enhance- 1060 psi Volume % ment solvent, g of g of (ml) product product HYDROLYSIS OF BENZYL CHLORIDE o2sns a 89 140 80 20 37 1.0720 3 95 145 B 10 2 1255 3s 96 us 1% 9 n 1.50 ES 7 96 B n 15 25140 Eo 66 Ba 31 16 100 35/50 * 4“ 149 : 106 osno 3 50 295 o2sns 3 39 24 1.070 3 39 144 HYDROLYSIS OF N-PHENYLBENZAMIDE o5)s 8 6 21 Loto 8 ar 246 2525 8 35 199 ESTERIFICATION OF BENZOIC ACID WITH 2-BUTANOL** 100 8 3 233 2.020 8 49 n 3.080 8 2 32 ‘+ “These reactions were done by heating the reaction mixture at power level 9 (720 watts) until the pressure in the vessel reached 60 psi. Then, the pressure was kept constant by heating the mixture for short intervals at 720 watts. ** The same concentrations of reagents were used in each reaction, the relative amounts being: 0.01 mol of benzoic acid, 0.10 mol of 2-butanol, and 10 drops of conc. HoSO4. International Microwave Power Institute 15TABLE 10 Product composition for reactions carried out under reflux and microwave conditions. Starting Materials Heating Method 1-bromooctane + microwave CH3ONa |L-bromooctane + reflux CH3ONa 1-bromooctane + microwave t-BuONa_ 1 -bromooctane + reflux t-BuONa 2-bromooctane + microwave CH3ONa 2-bromooetane + reflux CH3ONa cyclopentadiene + microwave methylacrylate cyclopentadiene + reflux methylacrylate heating methods. The energy efficiency can be further increased by power programming. Microwave heating has not been found to alter the composition of products of a chemical reaction appreciably. ‘While small differences in product ratios are observed in reactions carried out under microwave and conventional heating, this appears to be merely a thermal effect and can be attributed to the higher temperatures used in microwave reactions, References god, S.,Gyoker, I, Bene, G.,Puskas,A., Vari,J.,Pinter, A., and Takacs,S. 1989. 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