Ceric ammonium nitrate (CAN) - A useful catalyst for the rapid and high-yield esterification of carboxylic acids and alcohols with special reference to steroid and other multi-functional natural products

Article abstract of DOI:10.1039/b005908k

Ceric ammonium nitrate (CAN) acts as a versatile catalyst for the esterification of carboxylic acids and alcohols, including steroids and other multi-functional natural products, in excellent yields under mild and convenient reaction conditions.

Full text of DOI:10.1039/b005908k

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Ceric ammonium nitrate (CAN)Èa useful catalyst for the rapid and
high-yield esteriÐcation of carboxylic acids and alcohols with special
reference to steroid and other multi-functional natural products
Papori Goswami and Pritish Chowdhury*
L e t t e r
Organic Chemistry Division (Natural Products), Regional Research L aboratory,
Jorhat, 785 006, India. E-mail: pritishchowdhury=yahoo.com
Received (in Montpellier, France) 21st July 2000, Accepted 21st August 2000
First published as an Advance Article on the web 13th November 2000
Ceric ammonium nitrate (CAN) acts as a versatile catalyst for
the esteriÐcation of carboxylic acids and alcohols, including
steroids and other multi-functional natural products, in excel-
lent yields under mild and convenient reaction conditions.
Scheme 1, can be rationalised on the basis of some experimen-
tal Ðndings: (i) catalytic amounts only of CAN are sufficient
for completion of the reaction and (ii) under our experimental
conditions, when an alcohol (1È11) was heated (55È60 ¡C) with
CAN in chloroform for a considerable period of time, no reac-
tion was observed and both reactants were recovered
unchanged. Further work on the action of CAN in a BaeyerÈ
Villiger type oxidation is in progress.
The method of protection of hydroxyl and carboxyl groups by
making their esters is an important reaction in synthetic
organic chemistry.1,2 Although a number of esteriÐcation
techniques have been reported in the literature, a great need
still exists for a simple and mild procedure for this transform-
ation,3,4 since most of these methods involve the use of toxic
reagents and catalysts, viz., acid chlorides, acid anhydrides
and catalysts like pyridine and its derivatives: DMAP,5h7 etc.
All the esters gave satisfactory IR, NMR and mass spectral
data. In the IR spectra all the alcohols (1È11) after ester-
iÐcation [to give 1(aÈe)È11(aÈe)] exhibited an additional band
at 1725È1735 cm~1 corresponding to the ester function
formed. In the 1H NMR spectra, all the formate esters (1aÈ
11a) exhibited a singlet at 7.8È8.1 ppm for the HCO proton,
all acetates (1bÈ11b) displayed an additional three-proton
singlet at 1.9È2.1 ppm for the ester protons, all the propionate
esters (1cÈ11c) showed an additional multiplet at 2.25È2.35
Some other catalysts used in esteriÐcation are BunN`F~,8
4
DBU,9 (C H ) N`MeCl~,10 Ph P(OSO CF ) 11 and tribu-
8
17 3
3
2
3 2
tylphosphine.12 Besides these examples, recent work on ester-
iÐcation includes the application of various metal triÑates, viz.,
Sc(OTf) ,13,14 Yb(Otf) ,15 TMSOTf,16 etc.
ppm for the OCH protons and a methyl signal at 1.1È1.25
2
3
3
ppm, while all the butyric acid esters (1dÈ11d) exhibited an
Recently, the development of new synthetic methods and
reactions using new and environmental friendly reagents is
becoming more attractive. We describe here a very simple
method of esteriÐcation of carboxylic acids using ceric
ammonium nitrate (CAN) as the catalyst, which eliminates the
use of various toxic and costly catalysts and reagents generally
used in esteriÐcation processes. The reaction can be carried
out simply under mild heating of a mixture of a carboxylic
acid and an alcohol as such, or in an organic solvent in the
presence of a catalytic amount of CAN, giving excellent yield
of the ester. The results obtained for various alcohols (1È11)
with a number of di†erent carboxylic acids (AÈE) using CAN
are given in Table 1. The esteriÐcation of both primary and
secondary alcohols based on steroid and other multi-
functional natural products, as shown in Table 1, proceeded
smoothly and the yields of all the esters [1(aÈe)È11(aÈe)],
including the sterically hindered macrolide 6, were very high.
Therefore, ceric ammonium nitrate can be regarded as an effi-
cient catalyst for the rapid and high-yield esteriÐcation of car-
boxylic acids with primary and secondary alcohols. Under
similar reaction conditions tertiary alcohols and aromatic
acids are not esteriÐed. Thus, when tertiary alcohol 9 was
treated with carboxylic acids AÈE, or when the aromatic acid
6@ was subjected to esteriÐcation with methanol or ethanol, no
reaction took place and the starting materials were recovered
quantitatively.
additional multiplet at 2.20È2.35 ppm for the OCH protons,
2
a methylene signal at 1.20È1.25 ppm and a methyl signal at
0.95È1.1 ppm. In addition, all the esters [1(a-e)È11(a-e)] dis-
played the correct molecular ion (M`) in the mass spectra.
Experimental
Melting points were determined in capillaries and are uncor-
rected. IR spectra were recorded in a PerkinÈElmer 237 B
grating spectrophotometer on chloroform solutions. 1H NMR
spectra were recorded on a Varian T-60 NMR instrument in
deuterio-chloroform using TMS as the internal standard.
Mass spectra were scanned on an INCOS 50 GC-MS instru-
ment. TLC was performed on silica gel (E. Merck) and the
plates were activated at 100 ¡C before use.
CAN is known for e†ectuating various chemical transform-
ations, such as nitration,23 nitroacetamidation,24 cleavage of
acetals and ketals,25,26 formation of the ““red complexÏÏ with
alcohols by co-ordination with oxygen,27 etc. Although the
actual mechanistic details of the present esteriÐcation process
are not known, a possible path for this reaction, as given in
Scheme 1
DOI: 10.1039/b005908k
New J. Chem., 2000, 24, 955È957
955
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Table 1 EsteriÐcation of steroid and other natural product based alcohols with carboxylic acids AÈEa catalysed by ceric ammonium nitrate
(CAN)
Alcohola
Estera
Yieldb (%)
m/zb
mpb/¡C
95
98
90
90
95
414
428
442
456
112
114
113
97
1
1aÈe
530, 532c
130
90
98
90
92
96
416
430
444
458
117
110
109
99
2
2aÈe
3aÈe
532, 534c
130
95
98
92
90
95
342
356
370
384
180
170
168
150
201
317
458, 460c
90
98
90
88
95
378
392
406
420
157
154
150
135
180
418
518
4aÈe
5aÈe
494, 496c
95
98
93
90
95
376
390
404
418
È
È
È
È
È
492, 494c
98
93
90
92
95
508
522
536
550
100
98
92
80
130
619 R \ H, R@ \ Me
6@ R \ OAc, R@ \ H
6aÈed
624, 626c
90
98
95
92
90
278
306
334
362
È
È
È
È
È
7e, 20
7aÈe
570, 572c
95
98
95
92
95
136
156
164
178
È
È
È
È
È
8
8aÈe
Èd
252, 254c
È
È
È
921
956
New J. Chem., 2000, 24, 955È957

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Table 1 Continued
Alcohola
Estera
Yieldb (%)
m/zb
mpb/¡C
98
93
90
92
95
266
280
294
308
È
È
È
È
È
1022
11e
10aÈe
11aÈe
382, 384c
98
93
90
92
95
118
146
174
202
È
È
È
È
È
350, 352c
a The reactant carboxylic acids and alcohols, along with the product esters, are deÐned on Scheme 1. b Yields of the pure isolated esters, their
molecular ions [M]` and the melting point of all solid esters are given in the order NaÈe within each group corresponding to the reaction of
alcohol N with the 5 carboxylic acids AÈE. c The e esters show two molecular ion peaks due to the 35Cl and 37Cl isotopes. d No reaction was
observed with 6@ or with 9. e The diester was formed in all cases.
8
9
S. L. Beaukage and K. K. Ogilvie, T etrahedron L ett., 1977, 1691.
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10 V. Bocchi, G. Casanti, A. Dossena and R. Marchelli, Synthesis,
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11 J. B. Hendrickson and S. M. Schwartzman, T etrahedron L ett.,
A mixture of an alcohol (1.5 mmol) and a carboxylic acid (1.5
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the presence of ceric ammonium nitrate (0.10 mmol) for a
period of 30È60 min. The reaction was followed by TLC.
Chloroform was added if necessary to dissolve the acid or
alcohol used in the reaction. To work up the reaction the
mixture was poured into cold water (100 ml) and extracted
with petroleum ether (2 ] 100 ml). The organic extract, after
drying over anhydrous sodium sulfate, was evaporated under
reduced pressure to obtain the product ester, which was
further puriÐed by preparative TLC. Since the reactions with
all the substrates were carried out on a small scale with a
minimum amount of CAN, the catalyst could not be recycled
and went into the aqueous phase during work-up.
1975, 277.
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Acknowledgements
The authors thank the Director, RRL Jorhat, for providing
facilities necessary for this work. One of us (P.G.) thanks
CSIR, New Delhi, for a Senior Research Fellowship. The
Quality Control Management Centre of this laboratory is also
gratefully acknowledged for IR, NMR and mass spectral data.
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