Preparation of Methyl m-nitrobenzoate via Nitration

Amber Iverson Department of Chemistry Pacific Lutheran University Tacoma, WA 98447 iversoai@plu.edu Submitted 11/22/2006

Abstract: Nitration is an example of electrophilic aromatic substitution, and in this experiment the goal was to successful add a nitro group to methyl benzoate using nitric acid and sulfuric acid as a reagents, and vacuum filtration and centrifugation for isolation. The percent yield from the original reagents was 26%, and the nitro group was successfully added to the aromatic structure, which can be seen in the IR spectra of the final product.

The arenium ion is then deprotonated to reform the aromatic ring and yield the final product (Methyl-m-nitrobenzoate) with the newly attached nitro group. and can react with the aromatic compound (in this experiment Methyl benzoate) to form an arenium ion intermediate. or aspirin. aromatic ether linkages can be effectively created using nucleophilic aromatic substitution (SNAr). Another example of electrophilic aromatic substitution is the Kolbe reaction. where a nitro (NO2) group is being substituted for a hydrogen on an aromatic compound.2 This reaction is used in the synthesis of aspirin. The most common use of polyarylene ethers are in high-performance engineering plastics. which is then protonated to form the salicylic acid. Aspirin is a high selling commercial drug that utilizes electrophilic . The Kolbe reaction creates salicylic acid when sodium phenoxide attacks a carbon dioxide molecule.3 Polyarylene ethers are examples of aromatic ether linkages that are found in nature and can be synthesized using aromatic substitution. Aromatic substitution reactions are important synthetic reactions that are used to make a variety of products including high-performance plastics and acetylsalicylic acid (more commonly known as aspirin). then undergoes tautomerization to form sodium salicylate. The nitronium ion is a strong enough electrophile. This is achieved by the formation of the nitronium ion via protonation of nitric acid from sulfuric acid. In a study published in 2001 in the Journal of the American Chemical Society.Introduction: Nitration is an example of an electrophilic aromatic substitution reaction. which would be nitration). The salicylic acid is then reacted with acetic anhydride to synthesize acetylsalicylic acid. where carbon dioxide is used as the electrophile (instead of the nitro group.

and various other forms of substitution reactions are used for a variety of syntheses. The nitroaniline isomers precipitated during this step. a mixture consisting 1.aromatic substitution reactions. Three grams of acetanilide was mixed with 5 mL of concentrated sulfuric acid. The precipitated nitroaniline was collected using a . The dry product was weighed for recovery. The reaction mixture was warmed to room temperature and reacted for 15 minutes. After 20 minutes. Crystals were isolated using vacuum filtration with a Büchner Funnel. After the flask was cooled in an ice bath. The dilute sulfuric acid already present in the flask served as the hydrolyzing medium. A suspension of nitroacetanilide isomers resulted. The reaction was stopped when poured over 50g of crushed ice which also precipitated our product. the mixture was heated. The crystals were washed twice with 25 mL cold water followed by two washes with 10 mL ice cold methanol. 25 mL of ice water was added. Heating the mixture allows the solids to dissolve. including the time required for adding the nitric-sulfuric acid mixture. The reaction was cooled after each addition of acid by swirling in the ice bath. The acetanilide was dissolved swirling and stirring the mixture.8 mL of concentrated nitric acid and 5 mL of concentrated sulfuric acid was added dropwise using a disposable pipet. To hydrolyze the nitroacetanilides to their corresponding nitroanilines. Methodology: In a beaker I combined 6.1g methyl benzoate with 12 mL concentrated sulfuric acid. The mixture was cooled to 0C prior to the addition of 8 mL of an equal volume mixture of sulfuric and nitric acids. The flask was cooled in an ice bath and 30 mL of concentrated aqueous ammonium hydroxide was added.

along with 4 mL of dichloromethane. was added to the reaction apparatus over a 15 minute period. After boiling. they were dried in air and weighed.Büchner funnel. when the first crystals appeared. and the first crystals appeared. 1. The dry material was added to hot ethanol and dissolved. swirling frequently. The solid was washed with small amounts of water (total about 50 mL). reaction was allowed to proceed for 30 minutes. The crystals were wash with a minimum amount of cold ethanol and allowed to dry. the flask was placed in an ice bath. The aqueous layer was . After this addition. Add 2. After addition was complete. 1. The charcoal was removed by gravity filtration.The cooled suspension of aluminum chloride and methylene chloride was stirred using a stirring bar. The reaction mixture was poured into a mixture of 10g of ice and 5 mL of concentrated hydrochloric. Using a separatory funnel. This solution was mixed thoroughly for 10 to 15 minutes. Crude p-nitroaniline was dissolved in 15 mL ethanol for each gram of p-nitroaniline and the solution warmed to dissolve the solid.8 g of anhydrous aluminum chloride to the 5 mL methylene chloride in a 100 mL round bottom flask. the flask was stoppered. The sample was then air dried.4g of toluene was dissolved in 3 mL of dichloromethane.5g of activated charcoal was added to the solution and swirled for a few minutes. the organic layer was collected and saved. The filtrate was concentrated to about 1/3 of its original volume by heating on a hot plate. the flask was placed in an ice bath to complete the crystallizaiton. When the solution cooled. Addition of the toluene mixture occured over 20 minutes. After the crystals were collected. Crystals of p-nitroaniline were collect by vacuum filtration.6g of acetyl chloride. About 0. After adding all the dichloromethane.

The addition of the mixture allowed the nucelophile (methyl benzoate) to attack the electrophilic nitronium ion forming the arenium carbocation intermediate. Nitric acid isn’t a strong enough electrophile to react with the aromatic benzene ring. then a mixture of concentrated sulfuric acid and concentrated nitric acid (3) was added. Then the conjugate base from the deprotonation of the sulfuric acid (HSO4-). but the nitronium ion with the positive charge on the nitrogen is a strong electrophile and can react with the double bond of the methyl benzoate. The two organic layers were combined. methyl benzoate underwent an electrophilic substitution reaction to form Methyl-m-nitrobenzoate.1 The sulfuric acid /nitric acid mixture was necessary to form the nitronium ion from the nitric acid. The organic layers were washed with 10 mL of saturated sodium bicarbonate solution and then dried with anhydrous magnesium sulfate.Nitronium Ion Formation The addition of the nitric/sulfuric acid mixture was added drop-wise over a period of 15 minutes to reduce the amount of by-product that could be formed in the reaction. where a nitro (NO2) group was added to the methyl benzoate in the meta position. removes a proton from the meta-intermediate . Scheme 01.extracted with 6 mL of dichloromethane. The Methyl Benzoate (1) was first mixed with concentrated sulfuric acid (2). Results and Discussion: In this experiment.

and at 1525. then impurities were removed using hot methanol and centrifugation.1 The IR spectra also shows the characteristic aromatic ring stretches (3092.84 the nitro group stretch which indicates that the experiment was successful in adding the nitro group. and yielding the final product. Percent Yield Calculations: .51. 1500-700. and 670). The melting point of the final product was 76. the mixture was cooled without stirring. The crude product was isolated via vacuum filtration.to reform the aromatic ring structure. and calculations are shown at the end of the paragraph. Scheme 02. then added to crushed ice to stop the reaction.9°C. which compared to the literature value (78°C) was close enough to suggest a successful addition of the nitro group. Methyl-mnitrobenzoate.6°C-78.Nitronium addition to Methyl benzoate Once the acid was added. The percent yield of the experiment was 26%.

and the centrifuge machine in the open lab were also used. there are 3 resonance arenium carbocation intermediates. Methyl-m-nitrobenzoate. which was a successful learning opportunity to see “nature’s laziness”.From the lab manual. the melting point apparatus.15 ml (. and then weighed to determine the actual weight of the methyl benzoate.1 . the procedure was followed and .002 mol) . The vial and air condenser were then submersed in a 250-ml beaker icebath. Additional reading on the subject allowed for the defense of the meta attack as opposed to the ortho or para attack of the nitro group.As seen in Scheme 02. Experimental Section: All chemicals used in this experiment were provided by the PLU stockroom.008 mol) concentrated sulfuric acid was added to the vial and the vial was then attached to an air condenser (to help hold the vial in place).210 (.45 ml (. para.0016 mol) methyl benzoate was added to a tared 3-ml conical vial. A vacuum filtration system was also assembled and used to isolate the product. so the meta attack is the most resonance stabilized (compared to the attack at either the ortho or para positions). While the percent yield was a little low for the experiment. with the positive charge at either the ortho. A chilled mixture of .0033 mol) concentrated nitric acid and . The meta attack on the methyl benzoate is the only attack that doesn’t yield have a resonance structure that isn’t highly unstable. The major product is the meta product due to the carboxyl and nitro groups both being powerful electron withdrawing groups. the melting point data and the IR spectra both support the notion that the nitro group was successfully added to the methyl benzoate. and the infrared spectrometer.15 ml (. or the desire to form the structure with the most stability and lowest energy of activation. or meta position.

methanol was boiled using an Erlenmeyer flask on a hot plate and then 4 drops of methanol was used to dissolve the crude product in the Craig tube. the mixture sat at room temperature for approximately 5 minutes and then was submersed in an ice-water bath for another 5 minutes for crystallization to occur.87 carbonyl-ester stretch. from 1500-700 aromatic ring stretching. 2961. CH3 (C-H) stretching.51. was weighed using a watch glass. The ice was allowed to melt and then the mixture (white and chunky consistency) was vacuum filtered using a Hirsch funnel wand washed with two 1-ml portions of cold water and two 0.0g crushed ice. C-H aromatic stretch. For recrystallization. Once dried. Final weight: .3-ml portions of ice cold methanol. aromatic C-H stretching References: . Methyl-m-nitrobenzoate. the reaction mixture was allowed to acclimate to room temperature in a 250-ml beaker with a water bath at room temperature for 15 minutes unstirred. it was transferred via Pasteur pipette into a 20-ml beaker containing 2. through the air condenser into the vial. melting point measured.84. 1715. 1525.08g Percent Yield: 26% Melting Point: 76. percent yield was calculated.9°C Infrared Spectra Frequencies: 3092. the crude product was weighed and then added to a Craig tube for recrystallization. Once the acid was added.sulfuric acid was added drop wise via a Pasteur pipette over a period of 15 minutes. and an infrared reading was taken. 670. After being dissolved. nitro-group stretch.21. After the mixture had sat. The final product.6°C-78. The Craig tube was then placed in the centrifuge machine to isolate the crystals from the mother liquor.

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1999. D.M.L. Kriz. R. Solomons. Graham. Sik Im and Kim. G. 2001. Craig B. 11071-11072 . CA.G.. T. Pavia. Lampman. 2004.S.. 2) Fryhle. G. Snag Youl.” Journal of the American Chemical Society.. Third Edition. NJ. Organic Chemistry: Eighth Edition.1) Engel. Introduction to Organic Laboratory Techniques: A Mircroscale Approach.: Hoboken.. Brooks/Cole: Pacific Grove. John Wiley & Sons Inc. “Meta-Activated Nucleophilic Aromatic Substitution Reaction: Poly(biphenylene oxide)s with Triflouromethyl Pendent Groups via Nitro Displacement.W. 3) Chung.

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