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.
Introduction:

Nitration is an example of an electrophilic aromatic substitution reaction, where a

nitro (NO2) group is being substituted for a hydrogen on an aromatic compound. This is

achieved by the formation of the nitronium ion via protonation of nitric acid from sulfuric

acid. The nitronium ion is a strong enough electrophile, and can react with the aromatic

compound (in this experiment Methyl benzoate) to form an arenium ion intermediate. 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.

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). In a study published in 2001 in the Journal of the

American Chemical Society, aromatic ether linkages can be effectively created using

nucleophilic aromatic substitution (SNAr).3 Polyarylene ethers are examples of aromatic

ether linkages that are found in nature and can be synthesized using aromatic substitution.

The most common use of polyarylene ethers are in high-performance engineering plastics.

Another example of electrophilic aromatic substitution is the Kolbe reaction, where

carbon dioxide is used as the electrophile (instead of the nitro group, which would be

nitration).2 This reaction is used in the synthesis of aspirin. The Kolbe reaction creates

salicylic acid when sodium phenoxide attacks a carbon dioxide molecule, then undergoes

tautomerization to form sodium salicylate, which is then protonated to form the salicylic

acid. The salicylic acid is then reacted with acetic anhydride to synthesize acetylsalicylic

acid, or aspirin. Aspirin is a high selling commercial drug that utilizes electrophilic
aromatic substitution reactions, and various other forms of substitution reactions are used for

a variety of syntheses.

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 reaction mixture was warmed to room temperature and reacted

for 15 minutes.

The reaction was stopped when poured over 50g of crushed ice which also

precipitated our product. Crystals were isolated using vacuum filtration with a Büchner

Funnel. The crystals were washed twice with 25 mL cold water followed by two washes

with 10 mL ice cold methanol. The dry product was weighed for recovery.

Three grams of acetanilide was mixed with 5 mL of concentrated sulfuric acid. The

acetanilide was dissolved swirling and stirring the mixture. After the flask was cooled in an

ice bath, a mixture consisting 1.8 mL of concentrated nitric acid and 5 mL of concentrated

sulfuric acid was added dropwise using a disposable pipet. The reaction was cooled after

each addition of acid by swirling in the ice bath.

After 20 minutes, including the time required for adding the nitric-sulfuric acid

mixture, 25 mL of ice water was added. A suspension of nitroacetanilide isomers resulted.

To hydrolyze the nitroacetanilides to their corresponding nitroanilines, the mixture was

heated. The dilute sulfuric acid already present in the flask served as the hydrolyzing

medium. Heating the mixture allows the solids to dissolve. The flask was cooled in an ice

bath and 30 mL of concentrated aqueous ammonium hydroxide was added. The nitroaniline

isomers precipitated during this step. The precipitated nitroaniline was collected using a
Büchner funnel. The solid was washed with small amounts of water (total about 50 mL).

The sample was then air dried.

The dry material was added to hot ethanol and dissolved. After boiling, when the

first crystals appeared, the flask was placed in an ice bath to complete the crystallizaiton.

Crystals of p-nitroaniline were collect by vacuum filtration. The crystals were wash with a

minimum amount of cold ethanol and allowed to dry. Crude p-nitroaniline was dissolved in

15 mL ethanol for each gram of p-nitroaniline and the solution warmed to dissolve the solid.

About 0.5g of activated charcoal was added to the solution and swirled for a few minutes.

The charcoal was removed by gravity filtration. The filtrate was concentrated to about 1/3 of

its original volume by heating on a hot plate. When the solution cooled, and the first crystals

appeared, the flask was placed in an ice bath. After the crystals were collected, they were

dried in air and weighed.

Add 2.8 g of anhydrous aluminum chloride to the 5 mL methylene chloride in a 100

mL round bottom flask. After adding all the dichloromethane, the flask was stoppered.The

cooled suspension of aluminum chloride and methylene chloride was stirred using a stirring

bar. 1.6g of acetyl chloride, along with 4 mL of dichloromethane, was added to the reaction

apparatus over a 15 minute period. After addition was complete, 1.4g of toluene was

dissolved in 3 mL of dichloromethane. Addition of the toluene mixture occured over 20

minutes. After this addition, reaction was allowed to proceed for 30 minutes, swirling

frequently.

The reaction mixture was poured into a mixture of 10g of ice and 5 mL of

concentrated hydrochloric. This solution was mixed thoroughly for 10 to 15 minutes. Using

a separatory funnel, the organic layer was collected and saved. The aqueous layer was
extracted with 6 mL of dichloromethane. The two organic layers were combined. The

organic layers were washed with 10 mL of saturated sodium bicarbonate solution and then

dried with anhydrous magnesium sulfate.

Results and Discussion:

In this experiment, methyl benzoate underwent an electrophilic substitution reaction

to form Methyl-m-nitrobenzoate, where a nitro (NO2) group was added to the methyl

benzoate in the meta position.

The Methyl Benzoate (1) was first mixed with concentrated sulfuric acid (2), then a

mixture of concentrated sulfuric acid and concentrated nitric acid (3) was added.1 The

sulfuric acid /nitric acid mixture was necessary to form the nitronium ion from the nitric

acid. Nitric acid isn’t a strong enough electrophile to react with the aromatic benzene ring,

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.

Scheme 01- 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. The

addition of the mixture allowed the nucelophile (methyl benzoate) to attack the electrophilic

nitronium ion forming the arenium carbocation intermediate. Then the conjugate base from

the deprotonation of the sulfuric acid (HSO4-), removes a proton from the meta-intermediate
to reform the aromatic ring structure, and yielding the final product, Methyl-m-

nitrobenzoate.

Scheme 02- Nitronium addition to Methyl benzoate

Once the acid was added, the mixture was cooled without stirring, then added to

crushed ice to stop the reaction. The crude product was isolated via vacuum filtration, then

impurities were removed using hot methanol and centrifugation. The percent yield of the

experiment was 26%, and calculations are shown at the end of the paragraph. The melting

point of the final product was 76.6°C-78.9°C, which compared to the literature value (78°C)

was close enough to suggest a successful addition of the nitro group.1 The IR spectra also

shows the characteristic aromatic ring stretches (3092.51, 1500-700, and 670), and at

1525.84 the nitro group stretch which indicates that the experiment was successful in adding

the nitro group.

Percent Yield Calculations:

 As seen in Scheme 02, there are 3 resonance arenium carbocation intermediates, with

the positive charge at either the ortho, para, or meta position. The major product is the meta

product due to the carboxyl and nitro groups both being powerful electron withdrawing

groups. The meta attack on the methyl benzoate is the only attack that doesn’t yield have a

resonance structure that isn’t highly unstable, 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, the melting point data

and the IR spectra both support the notion that the nitro group was successfully added to the

methyl benzoate. 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, which was a successful

learning opportunity to see “nature’s laziness”, or the desire to form the structure with the

most stability and lowest energy of activation.

Experimental Section:

All chemicals used in this experiment were provided by the PLU stockroom, and the

infrared spectrometer, the melting point apparatus, and the centrifuge machine in the open

lab were also used. A vacuum filtration system was also assembled and used to isolate the

product.

Methyl-m-nitrobenzoate- From the lab manual, the procedure was followed and .210

(.0016 mol) methyl benzoate was added to a tared 3-ml conical vial, and then weighed to

determine the actual weight of the methyl benzoate.1 .45 ml (.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). The vial and air condenser were then submersed in a 250-ml beaker ice-

bath. A chilled mixture of .15 ml (.0033 mol) concentrated nitric acid and .15 ml (.002 mol)
sulfuric acid was added drop wise via a Pasteur pipette over a period of 15 minutes, through

the air condenser into the vial. Once the acid was added, 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. After the mixture had sat, it was transferred via Pasteur pipette into a

20-ml beaker containing 2.0g crushed ice. 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 0.3-ml portions of ice cold methanol. Once

dried, the crude product was weighed and then added to a Craig tube for recrystallization.

For recrystallization, 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. After

being dissolved, 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. The

Craig tube was then placed in the centrifuge machine to isolate the crystals from the mother

liquor. The final product, Methyl-m-nitrobenzoate, was weighed using a watch glass, percent

yield was calculated, melting point measured, and an infrared reading was taken.

Final weight: .08g

Percent Yield: 26%

Melting Point: 76.6°C-78.9°C

Infrared Spectra Frequencies: 3092.51, C-H aromatic stretch; 2961.21, CH3 (C-H)

stretching; 1715.87 carbonyl-ester stretch; 1525.84, nitro-group stretch; from 1500-700

aromatic ring stretching; 670, aromatic C-H stretching

References:
 1) Engel, R.G.; Kriz, G.S.; Lampman, G.M.; Pavia, D.L. (1999). Introduction to

Organic Laboratory Techniques: A Mircroscale Approach, Third Edition.

Pacific Grove, California: Brooks/Cole.

2) Fryhle, Craig B., Solomons, T.W. Graham. (2004). Organic Chemistry:

Eighth Edition. Hoboken, New Jersey: John Wiley & Sons Inc.

3) Chung, Sik Im and Kim, Snag Youl. (2001). Meta-Activated Nucleophilic

Aromatic Substitution Reaction: Poly(biphenylene oxide)s with

Triflouromethyl Pendent Groups via Nitro Displacement. Journal of the

American Chemical Society, 11071-11072.

References:
1) Engel, R.G.; Kriz, G.S.; Lampman, G.M.; Pavia, D.L. Introduction to

Organic Laboratory Techniques: A Mircroscale Approach, Third Edition;

Brooks/Cole: Pacific Grove, CA, 1999.

2) Fryhle, Craig B., Solomons, T.W. Graham. Organic Chemistry: Eighth

Edition; John Wiley & Sons Inc.: Hoboken, NJ, 2004.

3) Chung, Sik Im and Kim, Snag Youl. “Meta-Activated Nucleophilic

Aromatic Substitution Reaction: Poly(biphenylene oxide)s with

Triflouromethyl Pendent Groups via Nitro Displacement.” Journal of the

American Chemical Society, 2001. 11071-11072