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Chris Myers

CHM 352

Kek project: Hydrolysis of benzonitrile and esterification of benzoic acid

Abstract

The purpose of this experiment was to synthesize naphthalen-2-yl benzoate

(ester) from benzonitrile (nitrile) using a two-step procedure. Acid hydrolysis of

the benzonitrile was carried out by using H2SO4 to produce benzoic acid. After

confirmation by TLC, melting point, and IR benzoic acid was then synthesized into

naphthalen-2-yl benzoate by an esterification reaction with 2-naphthol. TLC,

melting point, IR, and NMR confirmed the final product’s identity .

Introduction

The purpose of this experiment was to synthesize naphthalen-2-yl benzoate

from a given amount of benzonitrile. After reviewing literature it was suggested

that there were several ways to synthesize the product from the specific starting

material. In this experiment a two-step procedure was chosen. The first step of

synthesis involved hydrolysis of the benzonitrile to produce benzoic acid. The

second step of the procedure involved esterification of the benzoic acid with 2 -

naphthol to synthesize the final product napthalen-2-yl benzoate (Figure 1).

Figure 1. Reaction scheme

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The hydrolysis of benzonitrile can occur either under acidic or alkaline

conditions to result in the formation of benzoic acid. When a nitrile is hydrolyzed

the compound is basically reacting with water in a two-step process. During this

process the reaction initially produces an amide. The amide is then hydrolyzed to

ultimately produce a carboxylic acid, in this case benzoic acid. Since the reaction

between water and nitriles is extremely slow, heat is needed along with a catalyst.

As stated earlier this reaction can occur with several different catalysts. Basic

catalysts such as NaOH, or acidic catalysts like HCl1 or H2SO4 are all frequently used

in hydrolysis reactions. In this experiment the acid H2SO4 was the catalyst chosen

for the reaction. H2SO4 was chosen over HCl and NaOH due to a procedure in which

p-nitrophenylacetic acid is produced from p-nitrobenzyl cyanide. This procedure

turned a nitrile into a carboxylic acid under mild conditions with a theoretical yield

higher than any procedure using HCl or NaOH. It was expected that by following

this procedure with benzonitrile and H2SO4, a similar yield of benzoic acid would be

produced2.

The second step of napthalen-2-yl benzoate synthesis called for the

esterification of benzoic acid with 2-naphthol. Esterification, also, is not limited by

one type of catalyst and can make use of several reagents such as H2SO4, HCl,

Me2NSO2Cl with N,N-dimethylamine3, DCC/DMAP4, and TsCl with N-

methylimidazole5 to react with a carboxylic acid and alcohol. Initially Me2NSO2Cl

with N,N-dimethylamine was chosen for synthesis as this was used for an

esterification procedure between 3-phenylpropanoic acid and 1-octanol at

temperatures slightly above room temperature ultimately producing an ester with

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percent yields between 93-973. However, due to chemicals not being ordered, the

procedure switched last minute to using TsCl with N-methylimidazole as the

catalyst. This was chosen over the other reagents due to knowledge that N-

methylimidazole forms an extremely reactive ammonium intermediate by removing

the tosylate ester previously formed between the TsCl and the benzoic acid5. With

the addition of an alcohol (2-naphthol) it was predicted that the product

naphthalene-2-yl benzoate would form.

Results and Discussion

The first part of the experiment began by hydrolyzing the benzonitrile with

H2SO4, H2O, and heat to synthesize the intermediate product benzoic acid. In this

reaction the lone pair of the nitrogen was expected to react with and become

protonated by an H+ from the H2SO4. Next water should attack the carbon

connected directly to the nitrogen as a pi bond between the two gives its electrons

to the nitrogen. A proton transfer was expected and a lone pair on the oxygen forms

a pi bond to the carbon as the pi bond between the nitrogen and carbon gives its

electrons to the nitrogen. Water is expected to attack the non-benzene ring carbon a

second time. Another proton transfer is expected to take place (from the H2O)

making the leaving group NH3+. Oxygen is then expected to use a lone pair to create

a pi bond to the carbon, kicking out the NH3+. Lastly the H on the pi bonded OH+ is

expected to donate its electrons to the oxygen and be removed to form benzoic acid

(Figure2).

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In order to make the benzonitrile the limiting reagent high molar

concentrations of H2SO4 were used. It was suggested that such a high concentration

would possibly restrict the amount of water accessible for hydrolysis, ultimately

causing less benzoic acid formation. Therefore, water was added to the mixture

with a molar concentration four times higher than that of H2SO4 in order for

conditions to be favorable for hydrolysis and collisions with water to occur.

Confirmation of the benzoic acid product was based mainly off of three

pieces of evidence: TLC, melting point, and IR. When examining the R f values of the

TLC containing the standard benzoic acid (0.125) to the experimental (0.187) they

matched much more closely than to that of the experimental and standard

benzonitrile (0.750). In the second evaluation of the product, the experimental

melting point (118°-119° C) also matched closely to the benzoic acid’s literature

value melting point (122° C). The IR spectrum also showed significant evidence for

the synthesis of the desired product as there was a very broad peak from ~3500 cm-

Figure 2. Hydrolysis of benzonitrile (mechanism)

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1 to ~2500 cm-1 indicating a presence of a carboxylic acid OH group. A strong peak

at 1677.71 cm-1 was also observed, indicating the presence of a carbonyl C=O group

(IR attached). Lastly the product’s appearance was noted as a white/colorless

crystalline solid. This fell into the expectations of the known appearance of benzoic

acid. When combined, these pieces of evidence strongly suggest that the

benzonitrile had successfully been converted to benzoic acid.

The second part of the experiment involved the esterification of the benzoic

acid and the 2-naphthol to produce the final product naphthalene-2-yl benzoate. In

this reaction the catalyst amounts were based off of the molar equivalent of benzoic

acid (1 molar equivalent) produced in the first step. In respect to this amount the

TsCl had a molar equivalent of 1.2 and the N-methylimidazole had a molar

equivalent of 3. What was expected in this reaction was to form a tosylate as a lo ne

pair on the benzoic acid’s OH to attacks the sulfur on the TsCl, ultimately kicking out

the Cl-. Next the unmethylated nitrogen on the N-methylimidazole was expected to

form a tetrahedral intermediate by attacking the carbonyl carbon, as electrons from

the pi bond between the carbon and oxygen go to the oxygen. As a lone pair from

this oxygen was donated to form the pi bond again to the carbonyl carbon, it was

expected for the leaving group –OTs to be kicked out. As 2-naphthol was added to

the reaction it was expected for the a lone pair on the alcohol’s OH to attack the

carbonyl carbon, as electrons from the pi bond between the carbon and oxygen once

again go to the oxygen. A proton transfer was then expected to occur subsequently

kicking out the N-methylimidazole as a lone pair on the oxygen formed a pi bond to

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the carbon. This ultimately produces the desired final product of naphthalene -2-yl

benzoate (Figure 3).

Confirmation of the final product as naphthalene-2-yl benzoate was based off

of four pieces of evidence: TLC, melting point, IR and NMR. When examining the Rf

values of the TLC containing the naphthalene-2-yl benzoate (0.29) to the

experimental (0.30) they matched closely. In the second evaluation of the product,

obtaining a melting point was somewhat difficult as different melting point

instruments gave melting points that differed by as much as 15° C. However, after

finding one instrument that gave multiple measurements at the same temperature it

was found that the experimental product’s melting point (100°-101° C) matched

closely to the naphthalene-2-yl benzoate’s literature value melting point (105° C).

The IR spectrum also showed significant evidence for the successful synthesis of the

final product as the broad peak from ~3500 cm-1 to ~2500 cm-1, indicative of a

carboxylic acid, disappeared along with the 1677 cm-1. The spectrum also showed

Figure 3. Esterification of benzoic acid (mechanism)

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the appearance of a peak at 1730.11 cm-1 indicating the presence of an ester bond

(IR attached). When examining the 1H NMR spectrum no peaks were observed in

the 10-13 ppm range indicating presence of benzoic acid. Acetonitrile and 2-

naphthol peaks were also absent from the spectrum confidently suggesting that the

product formed was indeed a relatively pure naphthalene-2-yl benzoate (NMR

attached).

Experimental

Benzoic Acid: Benzonitrile (5.1157 g, 0.0419 mol), H2SO4 (20.17 mL, 0.365 mol), DI

water (26.00 mL, 1.46 mol) and a boiling chip were all added to a round bottom

flask and refluxed for 20 minutes. The reddish/brown mixture was then diluted

with 45.00 mL of DI water and cooled to 0° C. The solution was then suction filtered

and washed several times with ice water to recover solid product (5.21 g, 0.043 mol,

102.6% yield). Rf = 0.188 (chloroform).

IR 3072 2827 2554 1678 1601 1583 1497 1453 1420 1324 1288 1180 1128 1101

1073 1027 1000 931 805 683 666 cm-1

Naphthalen-2-yl benzoate: TsCl (9.59 g, 0.0503 mol) in CH3CN (70 mL) and a stir

bar were added to a benzoic acid solution (5.21 g, 0.043 mol) and N-

methylimidazole (10.0 mL, 0.1257 mol) in CH3CN (20 mL). This solution was then

cooled in an ice bath and stirred for 30 minutes. Dissolved in 20ml of CH3CN 2-

naphthol (6.9 g, .048 mol) was then added chilled mixture and stirred for 2 hours.

After mixing the CH3CN was removed by the rotary evaporator and the solid was

dissolved in 150 mL of a 1:1 mixture of water and 5% NaOH solution. This solution

was then mixed with a 1:1 volume amount of ether to extract the ester. This

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extraction was done three times with the total volume of ether used being 450 mL.

Next the organic phase was then washed with 500 mL of brine. To absorb all of the

water from the solution Na2SO4 was added to the mixture until clumps stopped

forming and powder Na2SO4 freely moved around the solution. The solution was

decanted into a round bottom and then rotary evaporated to remove the ether. This

left a very light pink/brown powdery solid behind (9.401 g, 0.038 mol, 90.7% yield).

Many tests were done to confirm product, thus mass will be lighter. Also the scale

used throughout entire experiment measures about 85% of actual mass. R f = 0.188

(chloroform).

IR 1730 1627 1597 1510 1451 1377 1354 1317 1272 1264 1238 1206 1176 1154

1136 1122 1078 1062 1024 1002 958 902 893 878 818 801 746 737 684 673 662

cm-1

1H NMR (resolution poor) 8.249 8.179 7.984 7.868 7.770 7.669 7.567

References

1Organic Syntheses; Wiley & Sons: New York, 1941; Collect. Vol. No. I, 406

2Organic Syntheses; Wiley & Sons: New York, 1941; Collect. Vol. No. I, 36

3Wakasugi, K.; Nakamura, A.; Tanabe, Y. N,N-dimethylamines; a novel and efficient

agent for esterification, amidation between carboxylic acids, and

equimolar amounts of alcohols and amines. Tetrahedron Letters, 2001, 42,

7427-7430.

4Wakasugi, K.; Nakamura, A.; Iida, A.; Nishii, Y.; Nakatani, N.; Fukushima, S.; Tanabe,

Y. Novel and efficient method for esterification, amidation between

carboxylic acids and equimolar amounts of alcohols, and amines utilizing

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Me2NSO2Cl and N,N-dimethylamines; its application to the synthesis of

coumaperine,a natural chemopreventive dieneamide. Tetrahedron Letters,

2003, 43, 5337-5345.

5Wakasugi, K.; Nakamura, A.; Iida, A.; Nishii, Y.; Tanabe, Y. Simple, mild, and

practical esterification, thioesterification, and amide formation utilizing p-

toluenesulfonyl chloride and N-methylimidazole. Adv. Synth. Catal. 2003,

345, 1209-1214