Efficiency in Synthesis of Butyl Acetate via Different Methods Shannon Blanford and Andrew Judson 170 Main Street Aurora NY 13026 Butyl Acetate was synthesized using two different methods: a single aliquot addition of reactant and a drop-wise addition of reactant. Butyl Acetate was observed and qualitative analysis was performed to determine the presence of the desired product; Single aliquot addition was found to produce a more pure product.
INTRODUCTION Butyl Acetate is a simple acetate (C5H10O2) that can be found in many different places in the biosphere. This acetate is distinguished by a scent reminiscent of apples, and can thus be incorporated into many artificial flavorings and scents. One of its more famous uses is for its mimicry of honeybee alarm pheromones. Along with isopentyl acetate, butyl acetate is one of the active components of a pheromone that worker bees release when they sting to warn the rest of the hive of an impending attack1. Pheromones are produced in the Koschewnikow gland of the honeybee, which is a constituent part of the sting sheath. When the stinger is unsheathed, chemical synthesis begins2. Butyl Acetate was found in one experiment to elicit a “medium” response in a majority of bees1. This pheromone could be highly useful in this field, as well as in the more well-known field of artificial scents. Butyl acetate can be easily artificially synthesized via a Fischer Esterification: n-butanol and acetic acid (or acetic anhydride) can be combined, refluxed, and distilled to create a single ester product. The purpose of this experiment is to determine which of two experimental procedures produces a greater percent yield of butyl acetate in order to increase efficiency of synthesis for use in honeybee research and in the field of artificial scents.
MATERIALS AND METHODS Addition of Reactant in 1 aliquot (n-butanol and acetic acid): 6 mL (0.0656 mol) of n-butanol was placed in a roundbottomed flask, to which 3.76 mL (0.0656 mol) of acetic acid and 0.35 mL (0.0066 mol) of sulfuric acid catalyst were added. The solution was allowed to reflux for 30 minutes. Following the reflux, a distillation was performed and the liquid produced between 71°C and 80°C was collected. 5334g (0.046 mol) of product was collected, resulting in a 109% yield. Dropwise Addition of Reactant: 6 mL (0.0656 mol) of n-butanol was placed in a roundbottomed flask and set up in a reflux apparatus. 3.10 mL (0.033 mol) of acetic anhydride was placed in a drop addition flask. The solution was stirred as the acetic anhydride was added to the n-butanol at a rate of 1 drop every 3 seconds.
Stirring continued for the duration of the addition of the acetic anhydride. The resulting solution was allowed to distill. The liquid produced between 71°C and 80°C was collected. 5.784 g (0.050 mol) of product was collected for a 119% yield.
DISCUSSION Qualitative observation suggested that the product of the single aliquot reaction was butyl acetate. The product smelled like true butyl acetate, but the reaction gave a 109% yield, which implies that the observed product was not a pure sample. Similarly, the dropwise addition product was also impure, given that the percent yield was over 100% (119%). However, the product from the drop-wise addition did not smell as distinctly as the product from the single aliquot addition, and so was not as convincingly composed of butyl acetate. The product from the drop-wise addition still had a tinge of acetic anhydride scent, which would indicate a strong presence of unreacted reagent in the distilled substance.
CONCLUSION The two methods of butyl acetate synthesis both produced more than 100% yield. These results would suggest that a more precise method of separation of products might be necessary in order to isolate a purer sample of the desired substance. However, qualitative observations from this experiment suggest that the single aliquot addition would be a more efficient procedure for the production of butyl acetate. The product of the single aliquot addition smelled strongly of apples, which is a telling indicator of the presence of butyl acetate in a product. Given butyl acetate’s importance in biochemical communication in honeybees, theoretically one way to test if the product contained a significant portion of butyl acetate would be to introduce a sample to a hive of honeybees and note if any change in behavior occurred.
Collins , A., & Blum, M. (n.d.). Bioassay of Compounds Derived from the Honeybee Sting. (1982). Journal of Chemical Ecology, 8(2), Breed, M, Guzman-Novoa E, & Hunt, G. Defensive Behavior of Honeybees: Organization, Genetics, and Comparisons with Other Bees. (2004). Annual Review of Entomology 49(271-298).
Figure 1: Mechanism for reaction of Butyl Acetate.
Cost Efficiency of Synthetic Vanillin Blair, Samantha B., Dunster, Lauren P., Fesko, Courtney V. Wells College. 170 Main Street, Aurora, New York 13026 ABSTRACT: Vanillin (4-hydroxy-3-methoxybenzaldehyde) is a commonly used phenolic aldehyde which is known for its aroma and flavoring. Natural vanilla extract is expensive and takes months as opposed to hours to process; therefore alternate methods of producing vanillin are in high demand. Its uses include food flavoring, perfumery, and the starting material in pharmaceutics. The purpose of this research was to synthesize 4-hydroxybenzaldehyde by means of bromination. This yields 3-bromo-4hydroxybenzaldehyde which undergoes copper-mediated coupling with methoxide to produce vanillin. The net loss of experimentally producing vanillin has an approximate cost of $3,473.14 per gram. When processing naturally formed vanilla, the net gain was $0.09 per gram. Ultimately, it is more cost-effective to process natural vanilla as opposed to synthesizing vanillin.
tyrosine into 4-coumaric acid, then into ferulic acid, finally into vanillin(Figure 1).
Japanese scientist, Mayu Yamamoto, won the 2007 Ig Nobel Prize for Chemistry for extracting lignin from cow dung, which could then be converted to vanillin. This was regarded as a great discovery as vanillin is in high demand synthesis alone cannot support the needed supply. This demand results from the many widespread uses of vanillin. It is most commonly found in vanilla plants, and is known for its distinct flavoring and aroma. These qualities make it a prime ingredient for food markets. The chocolate and ice cream industries comprise approximately 75% of the use of vanillin for flavoring, while other food uses include baked goods, vinegars, sodas, wines, and spirits. The aroma of vanillin also makes it desirable in perfumes and cleaning products. In the science community, it serves a different purpose- it is used in reactions by chemists and drug development by pharmaceutical companies. Several drugs that utilize vanillin include Ldopa, the Parkinsonâ€™s disease drug, the antibacterial compound Trimethoprin, and the heart drug Papaverin (Cotton, 2012). Vanillin is also used to develop thin layer chromatography plates. There are numerous ways to obtain vanillin; naturally, biosynthetically, and chemically. Naturally, vanillin is found in Leptotes bicolor, an orchid native to Paraguay and southern Brazil. Vanillin can also be extracted naturally from the seed pods of Vanilla planifola, a plant grown in tropical areas around the globe. Cured vanilla pods contain approximately 2% by dry weight vanillin in the form of the Î˛-D-glucoside (Cotton, 2012). For this process the seed pods are sunned during the day and wrapped in cloth at night to then be packed in airtight boxes to sweat. This lasts for approximately 1-2 weeks. The pods are then dried and aged for several months for premium aroma and flavor. The disadvantage of this process is the amount of time it takes to produce the final product (Dignum, 2001). Due to the length of the natural process, an alternate method of vanillin production has been sought. Biosynthetically, vanillin is produced by converting
Figure 1: Pathway showing Tyrosine converting to 4-coumaric acid, then to ferulic acid then vanillin. (Kumar, 2012)
Ferulic acid is converted to vanillin by converting the carboxylic acid to a thioester with acetyl-CoA. The feruloyl CoA is then hydrated to give 4-hydroxy-3-methoxyphenyl-Î˛ydroxypropionyl-CoA (HMPHP-CoA). There are two possible pathways to convert HMPHP-CoA into vanillin. One pathway begins with oxidation of the hydroxyl group, followed by cleavage to release acetyl-CoA to form a thioester. This then leads to cleavage of the thioester into an aldehyde. The other pathway contains one enzyme that would simultaneously oxidize the hydroxylgroup along with the release of acetylCoA (Figure 2) (Walton, 2003).
aqueous mixture was extracted with three 20mL portions of diethyl ether before being dried with Na2SO4 and gravity filtered (Taber, 2002-2006). The mass of the vanillin product was 1.45g (7.41x10-3 moles) prior to performing the column chromatography. After purifying the sample, there was a final mass of 0.07g (3.57x10-4 moles).
Figure 2. Pathway showing Ferulic Acid converting to FeruloylCoA and then to HMPHP-CoA. From there there are two possible pathways. One shown in red, shows oxidation of the hydroxyl group, then cleaved to release acetyl-CoA to form a thioester and then an aldehyde. The blue pathway shows simultaneous oxidation of the hydroxyl group and release of acetyl-CoA. Both pathways have the end result of vanillin shown in black. (Kumar, 2012).
Chemically, vanillin can be synthesized from guaiacol. In this process, guaiacol reacts with glyoxylic acid by electrophilic aromatic substitution. The result is vanillylmandelic acid, which is converted to vanillin via 4-hydroxy-3methoxyphenylglyoxylic by oxidative decarboxylation (Figure 3)(Walton, 2003).
The product of the gravity filtration was purified by column chromatography using ethyl acetate to elute the vanillin. 10:1 hexanes to ethyl acetate and finally was used as the solvent. The vanillin was rotary evaporated to give 0.07g of a yellow oil. The ‘H NMR indicated δ 4.0ppm, s, 3H; δ 6.3ppm, s, 1H; δ 7.1ppm, m, 1H; δ 7.4ppm, m, 2H; δ 9.8ppm, s, 1H.
DISCUSSION The ‘H NMR results indicate the presence of pure vanillin, with a singlet at 3.8ppm, 6.4ppm, and 9.8ppm, and multiplets at 7.1ppm and 7.4ppm. These values correspond with the -O-CH3 group, as well as the -OH and the –C=O group, all three of which come off of the benzene ring. The values from 7-8ppm indicate aromatic protons.
Figure 3. Guaiacol(1) undergoing electrophilic aromatic substitution resulting in vanillylmandelic acid(2). This is converted to 4-hydroxy-3-methoxyphenylglyoxylic(3), which then goes through oxidative decarboxylation to finally result in vanillin(4). (Kumar, 2012) For this experiment, Vanillin was also synthesized chemically, however by a different means.
METHODS AND MATERIALS 1.96g (0.025moles) of bromine was added to 25mL of methanol. 8.3 mL of this solution of was added to a separate flask, swirled and cooled in an ice-water bath for approximately five minutes. (0.004moles) of 4hydroxybenzaldehyde was added to the flask and swirled. The solution was quenched after 30 seconds by adding aqueous sodium bisulfite. The aqueous mixture was extracted with three 25mL portions of diethyl ether. This was dried over sodium sulfate, and then gravity filtered. In order to produce the crude product of 3-bromo-4hydroxybenzaldehyde, the resulting material was rotary evaporated to a pink powdered state. 0.2g of crude 3-bromo-4-hydroxybenzaldehyde and 2.3mL of sodium methoxide were placed in a 5mL reaction vial, mixed, and heated in a 100ᵒC oil bath for an hour. The solution was cooled to room temperature and acidified with 10mL 3M aqueous HCl until the solid was dissolved. The
Figure 3: Pure vanillin NMR. The amount produced was worth approximately $0.92 in the current market (assuming that the product was pure). For an equal sample of vanilla, the cost would be less than one cent. These values disregard the cost of the reactants necessary for production. Using current market values, it was determined that the cost of all chemical materials for this lab was $244.04 (2013). There was a net loss of $243.12, while vanilla samples produce a net gain of $0.09 per gram. The significant difference in these values contrasts with our original theory that synthesizing vanillin would be more cost effective than processing natural vanilla. However, pricing differences based on bulk value have not been factored into these calculations. More economically based research would be necessary for more accurate results.
CONCLUSION Although the chemical pathway explored in this experiment did not prove to be economically resourceful, it is im-
portant to explore other pathways to meet the high demand of vanillin, with economic feasibility.
ACKNOWLEDGMENT We would like to thank Dr. O’Neil and her assistants Heidi Schlager and Lorelei Meier for their guidance in the lab. We would also like to express our gratitude towards Wells College for the use of their laboratory, as well as the Department of Chemistry and Biochemistry at the University of Delaware for providing us with the steps necessary for the synthesis of vanillin.
(2013). Product Results. Sigma-Aldrich. Retrieved From http://www.sigmaaldrich.com/unitedsta tes.html Cotton, S. Chemistry in its element: Compounds. 2012. Retrieved from http://www.rsc.org/chemistryworld/podcast Dignum, Mark J. W.; Josef Kerlera, and Rob Verpoorte (2001). "Vanilla Production: Technological, Chemical, and Biosytheic Aspects". Food Reviews International 17 (2): 119–120. doi:10.1081/FRI-100000269. Kumar, R. (2012). A review on the vanillin derivatives showing vari ous biological activities. International Journal of PharmTech Research, 4(1), 266-279.
Taber, D.F. (2002-2006) Synthesis of Vanillin. Retrieved from http://valhalla.chem.udel.edu/vanillin.html Walton, Nicholas J.; Melinda J. Mayer, and Arjan Narbad (July 2003). "Vanillin". Phytochemistry 63 (5): 505–515. doi:10.1016/S0031-9422(03)00149-3.
The Production of Propyl Hexanoate Through Fisher Esterification and the Reaction of 1-propanol with Hexanoic Anhydride Melena R. Hagstrom, Ashley K. Roser Wells College, 170 Main Street, Aurora, NY 13026 ABSTRACT: Esters contain a carbonyl group attached to a singly-bonded oxygen that is also bonded to an alkyl group. These compounds are useful in the production of scents and flavors for modern commercial usage. This study compares two methods of producing propyl hexanoate, an ester that has the scent of blackberries: 1) Fisher esterification, and 2) the reaction of 1propanol and hexanoic anhydride. Production of the propyl hexanoate through Fisher esterification was found to be more efficient, producing a 58.50% yield, while the reaction of 1-propanol and hexanoic anhydride produced only a 25.36% yield.
Esters are compounds containing a carbonyl group and an ether bonded directly to the carbonyl carbon, and are used extensively as a source of scents in perfumes and as flavoring1. Propyl hexanoate is an ester produced naturally by yeast fermentation and found in wine, but can be artificially produced to provide a blackberry flavor for commercial product2. There are multiple ways in which esters can be synthesized, including Fisher esterification, and the reaction of an alcohol with an anhydride. This study examines the formation of propyl hexanoate via these two methods and compares the percent yield and purity of the propyl hexanoate synthesized. Fisher esterfication involves the reaction of 1-propanol and hexanoic acid in the presence of an acid catalyst (sulfuric acid).
Scheme 1. Formation of propyl hexanoate through the reaction of 1-propanol and hexanoic acid. (a) the oxygen is protonated to make the carbonyl carbon more electrophilic (b) 1-propanol performs a nucleophilic attack on the carbonyl carbon (c) the conjugate base of the acid catalyst deprotonates the 1-propanol oxygen. (d) the alcohol oxygen is protonated, allowing it to leave as water in (e). (f) the conjugate base of the acid catalyst deprotonates the oxygen, resulting in product (g).
Another method involves reacting 1-propanol with hexanoic anhydride, which does not require a sulfuric acid catalyst, as 1-propanol is a strong enough nucleophile to attack the activated carbonyl contained within the hexanoic anhydride and the hexanoate ion is a stable leaving group.
Scheme 2. Formation of propyl hexanoate by the reaction of 1propanol and hexanoic anhydride. (a) 1-propanol performs a nucleophilic attack on the carbonyl carbon. (b) hexanoate ion leaves. (c) the hexanoate performs a nucleophilic attack and deprotonates the oxygen, forming the final product (d).
EXPERIMENTAL DETAILS To a round bottom flask 150mmoles (11.22mL) of 1propanol, 136mmoles (17mL) of hexanoic acid, and 1mL of concentrated sulfuric acid were added with continuous stirring. The mixture was refluxed for one hour. After cooling to room temperature the mixture was transferred to a separatory funnel and washed with 50mL of deionized water. The aqueous layer was drained, and the organic layer was washed with two 5mL portions of 5% aqueous sodium bicarbonate. The product was dried with sodium sulfate to give 19.10 grams of crude product. The solution was rotary evaporated for ten minutes to give 17.96 grams of purified product. 'H NMR analysis revealed that 12.59 grams of this purified product was propyl hexanoate. To a round bottom flask 150mmoles (11.22mL) of 1propanol and 75mmoles (17.36mL) of hexanoic anhydride were added with continuous stirring. The mixture was refluxed for one hour. After cooling to room temperature the solution was rotary evaporated for ten minutes, to give 22.44 grams of crude product. The mixture was transferred to a separatory funnel and washed with 50mL of water. The aqueous layer was drained, and the organic layer was washed with two 5mL portions of 5% aqueous sodium bicarbonate. The product was dried with sodium sulfate but circumstances made it illogical to weigh the product. 'H NMR analysis revealed that 6.02 grams of this purified product was propyl hexanoate.
RESULTS From the solution of Fisher esterification 12.59 grams (79.56mmoles) of propyl hexanoate were obtained, the percent yield being 58.50%. From the reaction of 1-propanol with hexanoic anhydride 6.02 grams (38.04mmoles) of propyl hexanoate were obtained, the percent yield being 25.36%.
DISCUSSION AND CONCLUSION By analyzing 'H NMR spectra of the products of both methods, it was found that the Fisher esterification produced a greater percent yield of propyl hexanoate (58.50%) than the reaction between 1-propanol and hexanoic anhydride (26.77%). The Fisher esterification produced propyl hexanoate with twice the efficiency of the other method. This could be due to the fact that the substitution site on the
hexanonic acid where the alcohol was protonated (allowing it to leave as water while the 1-propanol performed a nucleophilic attack) was a less sterically hindered reaction site (Scheme 1). Another factor could be that the hexanoate ion is a worse leaving group than water. The carbon on the water molecule prompts it to leave to seek a more favorable, neutral structure, while the hexanoate ion gains a negative charge when it leaves (Scheme 2). Perhaps the most important factor to consider is the acid catalyst. The Fisher esterification required an acid catalyst to proceed, even under reflux. This is because the carbonyl carbon becomes more electrophilic, allowing nucleophilic attack by the 1-propanol. The acid was used to protonate the carbonyl oxygen, resulting in an oxygen with a positive charge and, through the inductive effect and resonance, increases the partial positive charge on the carbon, making it more electrophilic. The reaction between 1propanol and the hexanoic anhydride did not require an acid catalyst to proceed. Without the use of an acid catalyst, the carbonyl carbon was electrophilic enough to be attacked by a nucleophile. However, even though an acid catalyst was not needed, the reaction still produced less product than the Fisher esterification. It is possible that the reaction with the hexanoic anhydride would would result in more product than the Fisher esterification if an acid catalyst was used, as this acid would protonate the carbonyl oxygen. This would place two positively charged oxygens next to the carbonyl carbon, one through protonation and one through resonance. The carbonyl carbon would be extremely electrophilic and the reaction may proceed more to completion than without the catalyst. This would be another avenue for experimentation. The Fisher esterification may have a lower percent yield than was intended. 136 mmoles of hexanoic acid was used while 150 mmoles of 1-propanol was added. Since these two compounds react in a 1:1 ratio, only 136 mmoles of the 1-propanol would be used in the reaction. This may explain the excess of propanol seen in the 'H NMR spectrum of the Fisher esterification product, as 14 mmoles of excess 1propanol would be left in the solution. Using equa-mmolar of 1-propanol and hexanoic acid may have avoided this problem. The percent yield of the propyl hexanoate produced by the reaction of 1-propanol and hexanoic anhydride may have been unrealistically high. This would reveal an even greater difference in percent yield between the two methods. Overall, the Fisher esterification produced a higher percent yield than the reaction of 1-propanol and hexanoic anhydride. There were several possible explanations for this difference: an acid catalyst was used in the Fisher esterification but not in the anhydride reaction, and the hexanoic anhydride offered a more sterically hindered electrophile than the hexanoic acid.
ACKNOWLEDGMENT Acknowledgment should be given to Dr. Lauren O'Neil for her assistance in the planning, preparation, and execution of this experiment.
Kanna, Bhishm (n.d.). What are the Uses of Esters? Preserve Articles. Web. Accessed 20 April, 2013. <http://www.preservearticles.com/ 201101032308/uses-of-esters.html> Yeast Metabolome Database. Canadian Institutes of Health Research. Web. Accessed 29 April, 2013. <http://www.ymdb.ca/compounds/YMDB01347>
Determination of SN1 or SN2 Mechanism Based on ΔG Tim Lambert, Chris Ferraro Wells College, Aurora, NY 13026 ABSTRACT: Computational chemistry was utilized to determine the mechanism of substitution on several substrates. The substitution mechanism is either SN1, producing a carbocation intermediate, or SN2, which occurs in a concerted fashion without intermediates. It is known that when a large energy difference exists between a carbocation intermediate and the starting product, the mechanism will be SN2, as the intermediate is too energetically costly. When there is a small energy difference between the carbocation and the starting material, the mechanism will be S N1. This study also compares leaving group stability’s and how this effects the reaction mechanism
INTRODUCTION Mechanics calculations in chemistry use Newtonian physics or Quantum Physics to describe bonds, bond angles, and rotations. For this Reaction quantum chemistry studies the ground state of individual atoms and molecules, the excited states, and the transition states that occur during chemical reactions.
METHODS The experiment utilized the web-based computational chemistry package, WebMo. Each molecule was optimized at the B3LYP/6-31g* levels of theory to test examine the energy difference between the structure and its carbocation. For each test case, the neutral molecule, its carbocation and the free leaving group were all subjected to optimization and energy calculation. The energies were then compared to predict the reaction mechanism, SN1 or SN2.
RESULTS A chart was made displaying the differences between the energy of the neutral molecule, and the energies of the carbocation intermediate as well as the leaving group. It was determined that from 0 kcal/mol to ~162 kcal/mol the reaction will undergo SN1. Once the energy difference is greater than 162 kcal/mol, the molecule will begin to undergo SN2. Table 1 shows the raw data obtained from Webmo as well as calculations to find ΔG. It displays the molecule along with the energy in calculated kcal/mol. Table 1 also displays the structure of the carbocation intermediate along with the energy in calculated kcal/mol, as well as the energy of the leaving group and ΔG. (ΔG = (Energy of carbocation + Energy of leaving group) – Energy of molecule). Figure 1 arranges the molecules into a linear scale based on ΔG. Those molecules to the left of the bold line at 162 kcal/mol are expected to undergo SN1 while those to the right of that line are expected to undergo SN2.
DISCUSSION Substitution can take place in multiple steps or in one step. An SN1 reaction involves a molecule that takes two steps to complete the substitution mechanism. Since two steps are involved, there is a period in which the carbocation is formed. An SN2 reaction takes place in only one step, with the leaving group and the nucleophilic group switching without the carbocation ever being formed. The difference between these two mechanisms is due to energy differences between the carbocation and the starting molecule, what kind of carbon the leaving group is on (primary, secondary, or tertiary), and how good the leaving group is. The main factor in determining whether or not these molecules underwent SN1 or SN2 was whether the carbon was primary, secondary, or tertiary. The lowest calculated ΔG was that of compound 6. Compound 6 displays the leaving group on a secondary carbon and is in the benzyllic position (1 carbon away from the aromatic benzene). Compound 6 had such a small energy difference (-21.15 kcal/mol) that it was not displayed in Figure 1. All other molecules tested yielded energy differences much greater than that found in this molecule. The greatest energy difference was found in compound 7 which displays the leaving group on a primary carbon. The fact that compound 7 also has a good leaving group F3CCOO- makes the carbocation very unstable and unlikely to form the carbocation intermediate. The energy differences of all other compounds fell in between compounds 6 and 7. The energy difference at which substitution goes from SN1 to SN2 was determined to be at 162 kcal/mol. By computing the energy of a molecule, the energy of the carbocation, and the energy of the leaving group, it is possible to determine at which energy level carbocation is too unstable to be formed. Being able to predict whether or not a molecule will undergo SN1 or SN2 is important because molecules that undergo SN2 will keep their stereochemistry while those that undergo SN1 will not and a racemic mixture will be formed. Since the carbocation is formed, the mole-
cule is able to rearrange. This rearrangement makes it impossible to produce a pure substance. In some instances such as medicine production, that rearrangement can take a helpful medicine and turn it into a deadly poison. For that reason, being able to predict the type of substitution that will occur is
very important. A simple mistake such as producing a racemic mixture instead of a pure substance can lose people millions of dollars and they can have lawsuits on their hands.
ΔG(kcal/mol) Figure 1: The ΔG (energy difference between the carbocation intermediate and original molecule) is displayed for each molecule evaluated in the study, with blue-shaded region representing molecules that under-went SN1 reaction and the red-shaded region representing molecules that underwent SN2.
Table 1. Structures of reactant and products and the calculated ΔG (kcal/mol)
Diels-Alder Reaction of 2,4-Hexadien-1-ol with Maleic Anhydride Angelo Papagelos, Lindsey Guzewicz & Lauren Oâ€™Neil Wells College 170 Maine Street Aurora, NY, 13026 KEYWORDS (Diels-Alder, Undergraduate Organic Laboratory, 2,4-hexadien-1-ol, maleic anhydride, lactone, nuclear magnetic resonance, correlation spectroscopy) ABSTRACT: A reaction between 2,4-hexadien-1-ol and maleic anhydride in toluene was performed to yield a white crystalline product. This product was prepared with dueterated acetone to perform 1H-NMR, 13C-MNR and COSY experiments showing that the product of this reaction was not the predicted Diels-Alder adduct, but instead underwent intermolecular rearrangement to produce a lactone (cyclic ester compound).
INTRODUCTION Since the discovery of the Diels-Alder reaction between conjugated dienes and dienophiles, this form type of reaction has been used as a common demonstration on many graduate, and undergraduate levels. On the undergraduate level, the Diels-Alder reaction is mainly studied by mechanistic means; with little time spent in the laboratory, this can lead to conceptual misunderstandings as to what the structure of the actual products of the reaction. The only way to truly see what happens over the course of a Diels-Alder experiment is to run it in the laboratory, and analyzing the products. For a reaction between trans,trans-2,4-hexadien-1-ol (1) and maleic anhydride (2), the expected Diels-Alder adduct (3) is not observed as the final product, instead, the observed product is a lactone (4), the product of intermolecular rearrangement
Scheme 1. Rearrangement of Diels-Alder adduct
A lactone is defined as a cyclic ester compound, and is formed in this case by cleavage of the anhydride by the alcohol group of the Diels-Alder product (McDaniel & Weekly, 1997). By analyzing the product of this reaction using 1HNMR, 13C-NMR and COSY this intermolecular rearrangement is verified.
METHODS AND MATERIALS 2.01g (20.4 mmol) of Maleic Anhydride was dissolved in 12.8mL of Toluene in a 50mL round bottom flask and heated until all the Maleic Anhydride was dissolved. To this solution 2.00g (20.4 mmol) of 2,4-hexadien-1-ol was added, and refluxed for approximately 90 minutes. At forty-five minutes, one hour, and one hour and fifteen minutes fluorescent TLCâ€™s with ethyl acetate were taken to compare the presence of Maleic Anhydride, 2,4-hexadien-1-ol, and the product to ensure that all the reactants were used in the reaction. Rf values were calculated (Table 1). The product was placed in an ice bath until a precipitate formed. The solution was vacuum filtered with cold toluene and the melting point was taken. The product was dissolved in D6-acetone, and Proton NMR, Carbon NMR, and COSY experiments were run (Figures 1,2 &3).
Compounds TLC - 45 Minutes Maleic Anhydride 2,4-hexadien-1-ol Product
Rf Values Rf (cm) 0 and 0.71 0.56 and .75 0 and 0.79
TLC - 60 Minutes Maleic Anhydride 2.4-hexadien-1-ol Product
Rf (cm) 0 and 0.82 .02 and .62 and .73 0 and 0.42
TLC - 75 Minutes Maleic Anhydride 2,4-hexadien-1-ol Product
Rf (cm) 0 and .75 .03 and .55 0 and .4
Table 1. Calculated Rf values.
From the reaction 2.4093g of product were obtained. The melting point of the product was measured at 138-140˚C. Rf values were calculated (Table 1). From the 1H-NMR spectra 8 proton environments were observed (Fig 1). Coupling between protons was also observed within the COSY spectra (Fig 2) and from the 13C-NMR spectra 9 distinct carbons were found (Fig 3). DISCUSSION From analysis of the melting point obtained (138-140˚C) it can be concluded that the product was impure, seeing as the reported melting point of the product should be (161˚C). This agrees with the TLC that was performed at forty-five, sixty, and seventy-five minutes, which show through Rf values that not all of the reactants were used up in the reaction, and some remained (Table1). From the 1H-NMR spectrum obtained assignments can be given to the doublet at 1.2ppm, which correspond to the methyl group protons, the peak at 2.0 ppm corresponds to the proton alpha to the methyl group, the peak at 4.1-4.4ppm correspond to the protons on the alkene, and finally the peak at 5.8ppm corresponds to the protons alpha to the cyclic ester (Figure1). Upon analysis of the COSY spectra obtained coupling between the proton alpha to the methyl group, and the methyl group protons can be seen (Figure 2). From the 13 C-NMR the peak at 205.134ppm corresponds to the carbonyl carbon of the carboxylic acid and the cyclic ester, the peak at 133.423ppm and 124.502ppm correspond to the alkene carbons, the peak at 70.491ppm corresponds to the carbon alpha to the ester, and the peak at 15.731ppm corresponds to the methyl group (Figure 3).
Figure 1. H-NMR spectra.
Conclusion: From the obtained spectra it can be concluded that the product of this Diels-Alder reaction has undergone an intermolecular rearrangement to form a lactone. By studying this reaction through the Diels-Alder style mechanism only, this conclusion could not be reached, only by doing the reaction, and analyzing the obtained spectra prove that sometimes there is more going on than would originally meet the eye. ACKNOWLEDGMENT We would like to thank Dr. O’Neil once again for providing the opportunity, and guidance through this laboratory experiment.
ABBREVIATIONS NMR, nuclear magnetic resonance. TLC, thin layer chromatography. COSY, correlation spectroscopy.
REFERENCES McDaniel, K. F., & Weekly, R. M. (1997). The diels-alder reaction of 2,4-hexadien-1-ol with maleic anhydride.Journal of Chemical Education, 74(12), 1465-1467. doi: 10.1021/ed074p1465
Figure 2. COSY spectra
The Diels-Alder Reaction, an Attempt to Obtain the EndoAdduct Savannah Tucker and Jamyra Young Wells College, 170 Main Street, Aurora, NY, 13026 ABSTRACT: In an attempt to isolate the endo product of a Diels Alder reaction, a reaction was observed over different time periods. The endo product could not be isolated or observed due to its instability caused by steric strain. The exo product forms regardless of the reaction time.
INTRODUCTION Conjugated dienes undergo addition reactions with alkenes that produce cyclohexene products. This reaction is called a Diels-Alder cycloaddition reaction; it forms two Carbon- Carbon bonds in one step and it is one of the few methods that can make cyclic molecules. This reaction occurs more rapidly when the dienophile has an electron withdrawing group because it draws electrons away from the reaction center. This gives the dieneophile of the reaction electron poor. When this reaction occurs an exo and an endo product can be formed. These two compounds are stereoisomers. The exo compound corresponds with the trans substituent’s and the endo compound with the cis substituent’s. Furan is a heterocyclic aromatic compound that undergoes a Diels Alder reaction as a diene. It forms a bicyclic compound with maleic anhydride, and the possible products produced are the exo (A) and/or endo (B) products mentioned previously. The endo product forms first, favored by kinetics, however it is the higher energy product. because of the instability caused by steric strain . The endo product forms the fastest; making it more favorable under kinetic control, but its instability forces it to for the more stable exo product. After a longer period of time the exo product is formed and completes the reaction because of its more stable conformation. In contrast, under thermodynamic control, the exo product is favored because of its stability. In order to observe the endo product the time span for the reaction to occur was altered to attempt to trap the endo adduct.
filtration and air dried. The product was recrystallized from hexanes and ethyl acetate, this product was weighed and the melting point was determined. This procedure was repeated two more times with reaction times of one day and 2.5 hours. The 1‘HNMR of the one week was obtained.1’HNMR: 6.5ppm, m(2.0H), 5.3ppm, m(2.0H), and 3.2ppm, s(2.0H).
RESULTS The mass of the one week reaction product was 0.82g (0.005 mol) and its melting point was 114-116°C, resulting in a 69.68% yield. This indicates that the exo adduct was the major product that formed. This result was repeated for the 24 hour reaction time, which had a mass of 0.0444g (0.00027 mol), a melting point of 116-117°C, and a 3.71% yield. The two and a half hour reaction produced no product, 0% yield.
CONCLUSION In conclusion, the results of the experiment all proved that the exo-product is favored in the Diels-Alder reaction regardless of time span. The melting points of both the one-week and one-day reactions were approximately 114.5 degrees Celsius which is the literature melting point for the exproduct. The 1‘H NMR showed peaks that correspond to the structure of the exo-product. The singlet peak at 3.2 shows two hydrogens containing no neighbors which is only found in the exo-product (A). The hydrogens of the endo-products each contain at least one neighbor.
EXPERIMENTAL DETAILS 1.20g (0.0122 mol) of finely divided maleic anhydride was dissolved in 10mL of anhydrous ethyl ether by warming in a water bath. Once cool, 1.00mL of furan (0.0157 mol) was added. This solution was covered, capped, and left to react for a week. The crystallized adduct was collected by vacuum
McMurry, J. Conjugated Compound and Ultraviolet Spectroscopy. Organic Chemistry Hybrid Edition, 8th ed.; Brooks/Cole Cengage Learning: California, 2012; pp 410-415. O’Neil, L. Diels-Alder Reaction of Maleic Anhydride and Furan, experiment #4.; Chemistry 214L: New York, 2012; p 1.
Synthesis of Benzyl Acetate Alexander E. Lamphear and Josalyn R. Ceroalo Wells College 170 Main Street Aurora New York, 13026 Aromatic Esters, Carboxylic Acids, Benzyl Alcohol, Benzyl Acetate, Esterification, Jasmine ABSTRACT: Esters are the source of many scents and flavors. They can be synthesized by Fisher Esterification, the reaction of a carboxylic acid with an alcohol in the presence of a catalyst. The synthesis of benzyl acetate, a compound that produces a jasmine scent, comes from the synthesis of benzyl alcohol and acetic acid. The role of the ratio of alcohol to acid was investigated. The results obtained were not conclusive.
INTRODUCTION Simple esters are among the numerous organic compounds that can be artificially synthesized. Many are found naturally in plants and animals and are responsible for the odor of a variety of fruits and flowers. Synthetic esters are manufactured for commercial use as artificial fruit essences in products like perfume1. These odors and flavors can be produced by a process called Fisher Esterification in which a carboxylic acid is heated with an alcohol in the presence of an acid catalyst (Scheme 1). The type of acid and alcohol determine what ester and smell or flavor is produced. For example, the banana scent is produced by isopentyl acetate, methyl butanoate smells like pineapples and octyl acetate smells like oranges.
using a pipette. The pH was tested and acid was added until the solution achieved a pH of approximately 3. To the remaining layer, 18 mL of toluene was added. The mixture was agitated and the aqueous layer removed. The product was purified by rotary evaporation and a 1H NMR was taken of the remaining product. The procedure was repeated increasing the amount of acetic acid from 100mmol to 300mmol. No product was isolated from this trial, so an NMR was unattainable.
Not all esters are used merely for their smell however. Ethyl acetate is a key component in nail polish remover and many other esters have medical uses1. This study uses benzyl alcohol and acetic acid to synthesize benzyl acetate, an ester found in many flowers and known to produce a pleasant aroma reminiscent of jasmine. The Fisher Esterification used to synthesize benzyl acetate is reversible. Adding acid pushes the reaction towards the products and increases the efficiency of the reaction. It is claimed that starting with an equimolar amount of alcohol and acetic acid would produce at most a 67% yield of benzyl acetate. Therefore, an excess of acetic acid is needed to produce a higher yield. This experiment tests the validity of this claim. If an equimolar amount of acid and alcohol produces just as much yield as using an excess of acid, the amount of acid used in synthesizing esters can be reduced, making the esters cheaper to produce.
EXPERIMENTAL DETAILS Using a reflux condenser (Figure 1), a solution of 100 mmol of benzyl alcohol, 100mmol glacial acetic acid and 1.0 mL of concentrated sulfuric acid were refluxed for one hour then cooled to room temperature. The mixture was washed with 50mL of deionized water and the aqueous layer was removed
Figure 1. Heating under reflux
RESULTS The reaction between benzyl alcohol and acetic acid in equimolar amounts yielded 12.58% product. The resulting compound was a translucent yellow liquid that smelled somewhat of jasmine, the desired scent. It can be assumed that some acetic acid and toluene were included in the 1.89 grams of product. The aroma was not of pure jasmine, but smelled slightly of vinegar and toluene suggesting the product was impure.
In the second reaction containing a 3:1 ratio of acetic acid to benzyl alcohol respectively, did not produce the expected product. The result was a thick, dark substance that smelled nothing of jasmine.
Scheme 1. Mechanism of the Fisher Esterification
CONCLUSION The results obtained in this experiment were not strong enough to prove that one reaction yielded more of the desired product than the other. The 3:1 acetic acid to benzyl alcohol reaction did not perform as planned and it is unclear what the end products were. The results obtained from the 1:1 reaction only gave a 12.58% yield and an NMR of the end product showed that it was impure. The source of the problem was believed to be the fact that the benzyl acetate did not form correctly. Rather than being a solid, like expected, the product was a hydrophobic liquid. The 1H NMR taken of the product of the 1:1 reaction suggested that it is possible that benzyl acetate was a component of the product but that there were too many impurities to be sure. In a future experiment, gas chromatography would be helpful in order to help determine the percent composition of benzyl acetate in the product.
AUTHOR INFORMATION All authors contributed equally.
ACKNOWLEDGMENT We would like to thank and acknowledge Dr. Lauren O’Neil for her guidance, encouragement and patience during this experiment. We would also like to thank the Wells College BCS Department for providing us with the lab and equipment necessary for our research.
REFERENCES 1. Fischer, W.H., A. G. Craig. “Microscale Esterfication of Peptides and Analysis by MALDI-ME.” http://www.salk.edu/LABS/pbl/brukeran1.htm. 10-02-2001. 2. http://www.chem.wisc.edu/areas/organic/orglab/tech/reflux.htm
The Cost Analysis of the Synthesis of Wintergreen and Pineapple Oil Levi M. Christman, Paige D. Fralick Wells College, 170 Main Street, Aurora, NY 13026 ABSTRACT: This report compares two esters; methyl salicylate (wintergreen oil) and ethyl butyrate (pineapple oil), to determine which ester was more cost effective for a chemist to synthesize. Seeing which ester is more cost effective can result in saving money for the Lifesaver company make more profit off of one other the esters. Results revealed that methyl salicylate was found to be the more cost effective ester compared to the ethyl butyrate, as it was only a 2-cent loss per mL rather than 25-cents loss per mL.
INTRODUCTION Esters are found in nature and are widely used in industry. Esters are responsible for the aroma of many fruits, including apples, pears, bananas, pineapples, and strawberries. Esterification is the process that is used to produce these esters. An ester is produced when a carboxylic acid is heated with an alcohol in the presence of an acid catalyst. The catalyst is usually a concentrated acid. Dry hydrogen chloride gas is used in some cases, but these tend to involve aromatic esters (ones containing a benzene ring). The esterification reaction is both slow and reversible. The equation for the reaction between an acid RCOOH and an alcohol R'OH (where R and R' can be the same or different) is as follows (see Scheme 1). These two esters are common and well known smells in Lifesaver candies and both appeal to the common consumer.
Scheme 1: The equilibrium reaction of general esterification.
METHODS Synthesis of Methyl Salicylate (Wintergreen oil) 0.8012 grams (0.0053 mol) of salicylic acid was added to a 25.0ml Erlenmeyer flask. 1.20mL (0.0297 mol) of methanol and 0.20mL of 3.0M Sulfuric Acid were added to the same flask. The contents were stirred briefly and heated in a water bath for 3 minutes. The flask was removed from the water bath and 3.00mL of water was added. The solution was gravity filtered and 0.2872g of solid was obtained. An 1H NMR of the methyl salicylate was obtained. Synthesis of Ethyl Butyrate (Pineapple oil)
1.20mL of ethanol (0.0206 mol) was added to a 25.0mL Erlenmeyer flask. 0.40mL (0.0042 mol) of butyric acid and 0.20mL of 3.0M sulfuric acid were added to the flask containing the ethanol. The contents were stirred briefly and heated in a water bath for 3 minutes. The flask was removed from the water bath and 4.0mL of water was added to the flask. The solution was distilled via simple distillation and 0.2971g of a clear liquid was obtained. A proton NMR spectrum was collected of the ethyl butyrate. Results and Conclusion The calculated percent yield of methyl salicylate was 31%. The calculated percent yield of ethyl butyrate was 9.66%. A cost analysis of the methyl salicylate and the ethyl butyrate was calculated. According to Sigma Aldrich, 2.6077g of ethyl butyrate was worth $0.09 and 2.8765g of methyl salicylate was worth $0.22. The starting materials for the ethyl butyrate ($0.34) were also more expensive than the starting materials used in the synthesis of methyl salicylate ($0.24). Thus it is more cost effective to synthesize methyl salicylate than ethyl butyrate because there is a 23-cent increase in profit.
ACKNOWLEDGMENT We would like to thank Dr. O’Neil for her assistance and guidance in our research, along with Heidi Schlager and Lorelei Meier for their laboratory assistance. We would also like to thank the Wells College Chemistry Department for access to the laboratory and provision of materials.
REFERENCES Clark, Jim. 2003.“Making esters from carboxylic acids and alcohols .The chemistry of the reaction “ <http://www.chemguide.co.uk/organicprops/alcohols/esterification. html>. Prices listed according to http://www.sigmaaldrich.com/unitedstates.htm