An Exceedingly Efficient and Chemoselective Esterification with Activated Alcohols Using AlCl3/NaI/CH3CN System

Article abstract of DOI:10.1081/SCC-120027277

A combination of hard Lewis acid AlCl₃ and a soft nucleophile NaI in acetonitrile has been used as an efficient system for the selective esterification reaction between aromatic carboxylic acid and alcohol.

Full text of DOI:10.1081/SCC-120027277

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An Exceedingly Efficient and Chemoselective
Esterification with Activated Alcohols Using AlCl3/
NaI/CH3CN System
N. N. Karade a , S. G. Shirodkar b , R. A. Potrekar a & H. N. Karade a
a School of Chemical Sciences, S. R. T. M. University, Nanded, 431606, India
b Netaji Subhash Chandra Bose College, Nanded, India
Version of record first published: 16 Aug 2006.
To cite this article: N. N. Karade, S. G. Shirodkar, R. A. Potrekar & H. N. Karade (2004): An Exceedingly Efficient and
Chemoselective Esterification with Activated Alcohols Using AlCl3/NaI/CH3CN System, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:3, 391-396
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 3, pp. 391–396, 2004
An Exceedingly Efficient and
Chemoselective Esterification
with Activated Alcohols Using
AlCl3/NaI/CH3CN System
2
1
N. N. Karade,1, S. G. Shirodkar, R. A. Potrekar,
*
and H. N. Karade1
1School of Chemical Sciences, S. R. T. M. University, Nanded, India
2Netaji Subhash Chandra Bose College, Nanded, India
ABSTRACT
A combination of hard Lewis acid AlCl3 and a soft nucleophile NaI in
acetonitrile has been used as an efficient system for the selective esteri-
fication reaction between aromatic carboxylic acid and alcohol.
Key Words: Esterification; AlCl3; NaI; Lewis acid; Catalysis; Alcohols;
Chemoselectivity.
*
Correspondence: N. N. Karade, School of Chemical Sciences, S. R. T. M. University,
Nanded 431606, India; E-mail: nnkarade@rediffmail.com.
391
DOI: 10.1081/SCC-120027277
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Karade et al.
INTRODUCTION
The carboxyl group is most frequently and popularly protected as the
benzyl, allyl, propargyl and t-butyl esters.[1,2] The advantages of these
activated esters over the corresponding methyl or ethyl ester derivatives are
attributed to its relative resistance to nucleophilic attack and its ready removal
under various mild condititions.[3,4] A number of papers and reviews have
been published on the synthesis of esters.[5–7] This reveals that the simple
condensation between carboxylic acid and alcohol in the presence of protic
and Lewis acids is a very useful and straightforward approach of all.[8,9] But
this strategy is extremely rare in the preparation of activated esters. As a
consequence, the preparation of activated esters include the use of less readily
available reagents/intermediates such a O-benzyl-S-propargyl xanthates,[10]
benzyl, ally, 2-phenyl-O-benzyl-isourea[13,14] and phenyldiazomethane.[15]
The major problem of handling isobutylene in the preparation of t-butyl esters
is recently overcome by using anhydrous magnesium sulphate and catalytic
sulphuric acid.[16] Although all of these methodologies afford the activated
ester in good yield, they suffer from drawbacks such as use of hazardous
reagents, vigorous functional group manipulation involving less readily
available reagents, long reaction time and incompatibility with other func-
tional groups. Herein we would like to report an efficient and selective method
for the esterification of aromatic carboxylic acid with activated alcohols using
a combination of hard Lewis acid (AlCl3) and a soft nucleophile (NaI) in
acetonitrile.
RESULTS AND DISCUSSION
The chemistry of AlCl3–NaI in acetonitrille has been widely studied
because it can be used in the selective demethylation of aliphatic methyl
ethers[17], regioselective ring opening of unsymmetrical cyclic ethers[18] and
in the conversion of oximes and amides to nitriles.[19,20] In the course of our
study to extend the scope of the AlCl3–NaI-acetonitrile system in organic
synthesis, we have found that aromatic carboxylic acids are effectively
esterified with stoichiometric amount of activated alcohols (Sch. 1).
Scheme 1.

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Chemoselective Esterification
393
We initiated the study by investigating the reaction of benzoic acid with
benzyl alcohol in the presence of AlCl3/NaI/CH3CN. When the above
reaction mixture is refluxed for 1 hour, benzyl benzoate was indeed formed in
69% yield.
Table 1 shows the representative results for the conversion of aromatic
carboxylic acids to the corresponding esters by using AlCl3–NaI reagent. The
present protocol for the esterification of aromatic carboxylic acids seems to be
very much general and flexible as it can accommodate a variety of alcohols
ranging from primary, secondary, tertiary and benzyl alcohols (entry 1–4).
Table 1. Esterification of aromatic carboxylic acid with alcohols using AlCl3/NaI
acetonitrile system.
Sr.
No.
Time Yielda,b
Acid
Alcohol
Ester
(h)
(%)
1
2
3
4
5
2
71
1
1.5
1
68
62
69
73
2
6
2
71
(continued)

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Karade et al.
Table 1. Continued.
Sr.
No.
Time Yielda,b
Acid
Alcohol
Ester
(h)
(%)
7
8
2
77
2
59
9
1
66
64
10
1.5
11
1.5
71
12
13
13
14
1
24
24
2
68
—
—
58
No reaction
No reaction
aYields refer to isolated products.
bAll the products were characterized by IR and H1-NMR.

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Chemoselective Esterification
395
The reaction of substituted aromatic carboxylic acid with allyl and propargyl
alcohol (entry 5–7) is also demonstrated to yield the corresponding esters in
good to high yields. The esterification of cinnamic and salicylic acid has also
not troubled in anyway by side reactions originating from participation of
double bond and 22OH group respectively (entry 10–12). Further investiga-
tion has established an important finding of chemoselectivity of the esterifica-
tion protocol because aliphatic carboxylic acid (entry 13–14) was found to be
inert under the same reaction conditions. Thus aromatic carboxylic acid can be
selectively esterified in the presence of aliphatic carboxylic acid.
EXPERIMENTAL
Typical experimental procedure: Aluminium chloride (2 mmol) and
sodium iodide (6 mmol) was added to dry acetonitrile (25 mL) and the mixture
was stirred magnetically for half hour at room temperature. Then stoichio-
metric amount of benzoic acid (1 mmol) and benzyl alcohol (1 mmol) was
added to the above reaction mixture and subjected to reflux for one hour. The
progress of the reaction was monitored by TLC. After completion of reaction
with respect to benzyl alcohol, water (25 mL) was added, extracted with
dichloromethane (2 Â 20 mL) and dried over anhydrous sodium sulphate. The
product was further purified by column chromatography over silica gel using
pet ether and ethyl acetate (9 : 1) to afford benzyl benzoate in 69% yield.
CONCLUSION
In conclusion, we have successfully demonstrated the role of AlCl3/NaI/
CH3CN system for an efficient and selective esterification process.
ACKNOWLEDGMENTS
We are thankful to the UGC, New Delhi for financial assistance.
REFERENCES
1. Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis;
John Wiley and Sons, Inc: New York, 1991.
2. Kocienski, P.J. Protecting Group; Gearg Thieme Verlag: New York,
1994.

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Karade et al.
3. Bergmann, M.; Zervas, L.; Salzmann, L.Ber. 1933, 66, 1288.
4. Johansson, R.; Samuelsson, B. J. Chem. Soc., Perkin Tran. I 1984, 2371.
5. Junzo, Otera Angew. Chem. Int. Ed. 2001, 40 (11), 2044 (and references
therein).
6. Lee, A.S.Y.; Yang, Hui-Chun; Su, F. Tetrahedron Lett. 2001, 42, 301.
7. Otera.. J. Chem. Rev. 1991, 93, 1449.
8. Haslam, E. Tetrahedron 1980, 36, 2409.
9. Dyke, C.A.; Bryson, T.A. Tetrahedron Lett. 2001, 42, 3959.
10. Tromeur, M.F.; Zard, S.Z. Tetrahedron Lett. 1998, 39, 7301.
11. Kokotos, G.; Chiou, A. Synthesis 1997, 168.
12. Thierry, J.; Yue, C.; Potier, P. Tetrahedron Lett. 1998, 39, 1557.
13. Vowinkel, E. Chem. Ber. 1967, 16, 100.
14. Wang, M.F.; Golding, B.T.; Potter, G.A. Synth. Commun. 2002, 30 (23),
4197.
15. Klemm, H.P.; Hintze, U.; Gercken, G. J. Chromatog. 1973, 19, 75.
16. Wright, S.W.; Hageman, D.L.; Wright, A.S.; McClure, L.D. Tetrahedron
Lett. 1997, 42, 7345 (and references therein).
17. Node, M.; Ohta, K.; Kajimoto, T.; Nishide, K.; Fujita, E.; Fuji, K. Chem.
Pharm. Bull. Japan 1983, 31, 4176.
18. Node, M.; Kajimoto, T.; Nishida, K.; Fujita, E.; Fuji, K. Tetrahedron Lett.
1984, 25, 219.
19. Konwar, D.; Boruah, M.; Sarmah, G.K.; Bhattacharyya, N.K.;
Borthakur, N.; Goswami, B.N.; Boruah, K.R. J. Chem. Research (S)
2001, 490.
20. Boruah, M.; Konwar, D. J. Org. Chem. 2002, 67, 7138.
Received in India July 31, 2003

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