Exp t 84 A Floral Fragrance Methyl Benzoate from K L Williamson Macroscale and Microscale Organic Experiments 2nd Ed 1994 Houghton Mifflin Boston p385 Revised 10 18 06 Prelab Exercise Give the detailed mechanism for the synthesis of methyl benzoate by Fischer Esterification Introduction The ester group is an important functional group that can be synthesized in a number of different ways The low molecular weight esters have very pleasant odors and indeed are the major components of the flavor and odor aspects of a number of fruits Although the natural flavor may contain nearly a hundred different compounds single esters approximate the natural odors and are often used in the food industry for artificial flavors and fragrances see table below In snapdragon flowers the volatile ester methyl benzoate is the most abundant scent compound It is synthesized by and emitted from only the upper and lower lobes of petals where pollinators bumblebees come in contact with the flower Emission of methyl benzoate occurs in a rhythmic manner with maximum emission during the day which correlates with pollinator activity Taken from http www plantcell org cgi content abstract 13 10 2333 In this experiment you will be synthesizing methyl benzoate via Fischer esterification Esters can be prepared by the reaction of a carboxylic acid with an alcohol in the presence of a catalyst such as concentrated sulfuric acid hydrogen chloride p toluenesulfonic acid or the acid form of an ion exchange resin O C H3C CH OH 3 OH O H H3C O CH3 H O 2 This Fischer esterification reaction reaches equilibrium after a few hours of refluxing The position of the equilibrium can be shifted by adding more of the acid or of the alcohol depending on cost or availability The mechanism of the reaction involves initial protonation of the carboxyl group attack by the nucleophilic hydroxyl a proton transfer and loss of water followed by loss of the catalyzing proton to give the ester Because each of these steps is completely reversible this process is also in reverse the mechanism for the hydrolysis of an ester Refer to your lecture textbook for the Fisher esterification mechanism scheme Other methods are available for the synthesis of esters most of them more expensive but readily carried out on a small scale For example alcohols react with acid anhydrides to form esters CH3CH2OH Ethanol O O O C C H3C H3C CH3 O Acetic anhydride O CH2CH3 CH3COOH Ethyl acetate Acetic acid Acid chlorides form esters by reaction with alcohols O CH3CH2CH2OH C H3C Cl Acetyl chloride 1 Propanol H3C O C O CH2CH2CH3 HCl n Propyl acetate In the latter reaction an organic base such as pyridine is usually added to react with the hydrogen chloride A number of other methods can be used to synthesize the ester group Among these are the addition of 2 methylpropene to an acid to form t butyl esters the addition of ketene to make acetates and the reaction of a silver salt with an alkyl halide See scheme below O H O OH O 2 Methylpropene Propionic acid H 2C C O Ketene t Butyl propionate O CH2O C CH3 CH2OH Benzyl alcohol Benzyl acetate O O O Ag Silver acetate O Br 1 bromo 3 methylbutane Isoamyl acetate As noted above Fischer esterification is an equilibrium process Consider the reaction of acetic acid with 1 butanol to give n butyl acetate O H3C C OH Acetic acid HOCH2CH2CH2CH3 n Butanol H O CH2CH2CH2CH3 C H2O O H3C n Butylacetate The equilibrium expression for this reaction is shown below O H3C C Keq O CH2 CH2CH2 CH3 O H3C C OH H2O HOCH2CH2CH2CH3 For primary alcohols reacting with unhindered carboxylic acids Keq 4 If equal quantities of 1butanol and acetic acid are allowed to react the theoretical yield of ester is only 67 at equilibrium To upset the equilibrium we can by Le Chatelier s principle increase the concentration of either the alcohol or acid as noted above If either one is doubled the theoretical yield increases to 85 When one is tripled it goes to 90 But note that in the example cited the boiling point of the relatively nonpolar ester is only about 8 C higher than the boiling points of the polar acetic acid and 1 butanol so a difficult separation problem exists if either starting material is increased in concentration and the product is isolated by distillation Another way to upset the equilibrium is to remove water This can be done by adding to the reaction mixture molecular sieves an artificial zeolite which preferentially adsorb water Most other drying agents such as anhydrous sodium sulfate or calcium chloride will not remove water at the temperatures used to make esters A third way to upset the equilibrium is to preferentially remove the water as an azeotrope Water can form an azeotrope with certain alcohols at specific concentrations A special apparatus called a Dean Stark apparatus or trap can be used to distill off the water as as an azeotrope while the ester being is formed Removing water from the reaction in this way will favor ester formation Synthesis of Methyl Benzoate by Fisher Esterification O OH O Benzoic acid mp 122 C MW 122 12 CH3OH Methanol bp 64 6 C MW 32 04 OCH3 H H2O Methyl Benzoate bp 198 199 C d 1 094 MW 136 15 Use the set up shown below this paragraph for this synthesis Place 5 0 g of benzoic acid and 25 mL of methanol in a 100 mL round bottomed flask cool the mixture in ice pour 1 5 mL of concentrated sulfuric acid slowly and carefully down the walls of the flask and then swirl to mix the components Attach a reflux condenser fitted with water inlet tubing add 3 boiling chips and reflux the mixture gently for 1 hr Isolation and Purification Cool the solution to room temperature then decant it into a separatory funnel containing 25 mL of water and rinse the flask with 25 mL of diethyl ether use wet ether found in a supply bottle in each hood Add this ether to the separatory funnel shake thoroughly and drain off the water layer which contains the sulfuric acid and the bulk of the methanol Wash the ether in the separatory funnel with 25 mL of water followed by 25 mL of 10 sodium bicarbonate to remove unreacted benzoic acid Again shake with frequent release of pressure by inverting the separatory funnel and opening the stopcock until no further reaction is apparent then drain off the bicarbonate layer into a beaker Wash the ether layer in the separatory funnel with saturated sodium chloride solution separate the ether solution and dry the ether solution over anhydrous calcium chloride in a 125 mL Erlenmeyer flask Add sufficient