Synthesis of 3-Carbethoxycoumarin, A Heterocyclic Compound

Janet Smith

Introduction

3-carbethoxycoumarin is a heterocylcic compound in the coumarin class.1

Although 3-carbethoxycoumarin is not widely used today for any specific processes,

coumarin compounds are used in many different processes today. The base compound of

this class of heterocyclic compounds, coumarin, occurs naturally in plants such as tonka

beans, lavender, cinnamon, and certain fruits such as strawberries and cherries. Coumarin

was discovered in the 1820s and was first synthesized in a laboratory in 1868.2 Today,

coumarin has practical uses in medicine.3 It has the ability to act as a blood thinner and

inhibit the growth of fungi and tumors.3 Coumarin derivatives, such as warafin, can also

be used as rodent poison.2

The synthesis of the coumarin compound, 3-carbethoxycoumarin that was done in

this experiment occurs through a transesterification, followed by an aldol condensation

reaction. A transesterification replaces a group attached to an ester with a different group

attached to an alcohol and an aldol condensation combines an enol and a carbonyl

compound to create a conjugated enone.4 The combination of diethyl malonate and

salicylaldehyde in piperidine and and ethanol under the correct conditions results in the

transesterification product:

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This transesterification product treated with ethanol, then results in the final product, 3-

carbethoxycoumarin:

The purpose of this experiment was to synthesize 3-carbethoxycoumarin from

salicylaldehyde and diethyl malonate. In order to isolate this compound the experiment

called for the use of refluxing and cooling for crystallization to occur. Infared

Spectroscopy analysis and 1H Nuclear Magnetic Resonance analysis was then called for

in order to confirm the identity of the product, 3-carbethoxycoumarin.

Experimental

3-Carethoxycoumarin. Salicylaldehyde (1.1mL), diethyl malonate (1.7mL), ethanol

(4mL), piperidine (20 drops), and glacial acetic acid (4 drops), were placed in a round-

bottomed flask (25mL) and stirred. The flask was connected to a water condenser, which

was connected to a plastic drying tube filled with Drierite and plugged at each end with

glass wool. The flask and attached apparatus was placed in a sand bath for heating on a

magnetic stirrer. The flask was refluxed for just under two hours. The flask was finally

cooled to room temperature and then was cooled in an ice bath. Once crystals appeared,

the contents of the flask were stirred for five minutes. The solid was then filtered off

using a Buchner funnel and allowed to dry. 1.496g of product was recovered. The

melting range, taken from a MelTemp device, for the product was 88°C to 91°C. In order

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to confirm the identity of the product, assumed to be 3-carbethoxycoumarin, an Infared

Spectroscopy analysis and 1H Nuclear Magnetic Resonance analysis were performed.

IR Data (see attached): Data of recovered product, 3-carbethoxycoumarin.

Significant Peaks
Observed Bond Strength
1449.7 cm-1 Aromatic ring
1602.6 cm-1
1754.2 cm-1 Ester

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H-NMR Data (see attached): Obtained using 35mg of product in deuterated chloroform
solvent on a 60MHz spectrometer.
Significant Peaks
Observed Splitting Pattern, Type of Hydrogen
1.415 ppm Triplet, —C-H3

4.49 ppm Quartet, —O—CH2—CH3

7.264 ppm Too difficult to determine because of many

different sets of overlapping equivalent
hydrogen atoms, Aromatic ring—H

Results and Discussion

The IR spectrum for 3-carbethoxycoumarin showed significant peaks at 1449.7

cm-1, 1602.6 cm-1, and 1754.2 cm-1. The peaks at 1449.7 cm-1 and 1602.6 cm-1 are a result

of the aromatic ring in the structure of 3-carbethoxycoumarin. The peak at 1754.2 cm-1

corresponds to the ester group in the structure. Both of these are condusive to the

structure of 3-carbethoxycoumarin. Other peaks seen on the spectrum may be a result of

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the complex structure of 3-carbethoxycoumarin or may be results of impurities formed in

the reaction.

The 1H-NMR spectrum showed significant peaks at 1.415 ppm, 4.49 ppm, and

7.264 ppm. All of these significant peaks showed that the product isolated is 3-

carbethoxycoumarin. The peak at 1.415 ppm was a triplet with an integral value set at

3.00. This peak corresponded to the methyl group in 3-carbethoxycoumarin. Another

significant peak, a quartet with an integral value of 1.43, was seen at 4.49 ppm, which

corresponded to the secondary hydrogens connected to the ester group in 3-

carbethoxycoumarin. The final significant peak was seen at 7.264 ppm corresponding to

the hydrogen atoms attached to the aromatic ring. The integral value of 3.81 ppm was

probably inaccurate due to the fact that there are four different sets of equivalent protons

attached to the aromatic ring and all of the equivalent protons had overlapping peaks seen

in the area. A small peak was seen at 8.5 ppm, which could have corresponded to the

indicated hydrogen:

Since this hydrogen was not seen in the spectrum and was placed in a fairly difficult

place to interpret where it would be on the 1H-NMR spectrum, it could have

corresponded to the indicated hydrogen, or it could have been an impurity.

The theoretical yield of 3-carbethoxycoumarin calculated from the amount of

salicylaldehyde (the limiting reactant) used, was 2.25g. Only 1.496g of 3-

carbethoxycoumarin was recovered however, resulting in a percent yield of 66.5%. Some

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of the reason for this error may have been loss of product in the Buchner funnel filtration,

an uncomplete reaction occurred due to too short of a reflux period, or human and

machine errors. The product had a melting range of 88°C to 91°C, which was comparable

to the actual melting point of, 92°C to 94°C.

Overall the synthesis of 3-carbethoxycoumarin was fairly successful. The sample

was fairly pure based both on the melting range, IR analysis, and 1H-NMR analysis. A

66.5% yield was recovered, which is fairly high for synthetic experiments.

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 References
1
“Synthesis of 3-Carbethoxycoumarin, A Heterocyclic Compound” handout. From

Al-awar, R., Wahl Jr., J. ‘Microscale Syntheses of Heterocyclic Compounds. J.

Chem Ed. 1990, 67, 265.

2
Coumarin. (2004, March 4). Retrieved from http://www.microscopy.fsu.edu/

phytochemicals/pages/coumarin.html
3
Phytochemicals. (n.d.). Retrieved from http://www.phytochemicals.info/phytochemicals/

coumarin.php
4
McMurry, J. (2008). Organic chemistry. Belmont, CA: Brooks/Cole, Cengage Learning.

Pages 808-813, 877-880.