A highly convenient, efficient, and selective process for preparation of esters and amides from carboxylic acids using Fe3+-K-10 montmorillonite clay

Article abstract of DOI:10.1021/jo0204202

In the presence of Fe³⁺-K-10 montmorillonite clay as a catalyst, aliphatic carboxylic acids selectively produced the corresponding esters in the presence of aromatic carboxylic acids by treatment with alcohols. Both the aliphatic and aromatic carboxylic acids formed the amides by reacting with the aliphatic amines, but only the aliphatic carboxylic acids yielded the anilides by treatment with aromatic amines. The catalyst is recoverable and recyclable.

Full text of DOI:10.1021/jo0204202

observed that Fe3+-K-10 montmorillonite clay is a highly
efficient catalyst for the esterification of aliphatic car-
boxylic acids in the presence of aromatic carboxylic acids.
Different aliphatic carboxylic acids, both conjugated and
nonconjugated, were treated with various alcohols in the
presence of the catalyst under reflux to obtain the
corresponding esters in high yields (Table 1). The aro-
matic carboxylic acids underwent no conversion under
similar conditions. The selectivity of the esterification of
aliphatic carboxylic acids has been demonstrated by
taking molecules with both types of carboxylic groups as
well as by competition experiments (Table 1). The
products were characterized from their analytical and
A High ly Con ven ien t, Efficien t, a n d
Selective P r ocess for P r ep a r a tion of Ester s
a n d Am id es fr om Ca r boxylic Acid s Usin g
F e3+-K-10 Mon tm or illon ite Cla y1
K. V. N. S. Srinivas and Biswanath Das*
Organic Chemistry Division I, Indian Institute of
Chemical Technology, Hyderabad 500 007, India
biswanathdas@yahoo.com
Received J une 20, 2002
1
spectral (IR, H NMR, and MS) data.
Abstr a ct: In the presence of Fe3+-K-10 montmorillonite
clay as a catalyst, aliphatic carboxylic acids selectively
produced the corresponding esters in the presence of aro-
matic carboxylic acids by treatment with alcohols. Both the
aliphatic and aromatic carboxylic acids formed the amides
by reacting with the aliphatic amines, but only the aliphatic
carboxylic acids yielded the anilides by treatment with
aromatic amines. The catalyst is recoverable and recyclable.
The catalyst used here can easily be prepared4 from
the readily available and inexpensive FeCl3 and K-10
montmorillonite clay. It can be safely handled. It can also
be recovered and reused. When K-10 montmorillonite
clay was used alone, the yields of the products were
somewhat lower (10-20%).
The catalyst, Fe3+-K-10 montmorillonite clay, is also
efficient for the preparation of amides from carboxylic
acids. There are some reagents that can be applied for
the one-step conversion of carboxylic acids into amides;2d,5
however, many of these reagents are not easily available
and expensive. Their preparations are also hard tasks.
Selectivity of the amide formation by using these re-
agents has been studied only in a few cases.2d Moreover,
complex experimental procedures, long reaction times,
and unsatisfactory yields are also certain drawbacks in
applying some of these reagents. Recovery of the catalyst
also creates a problem. However, Fe3+-K-10 montmoril-
lonite clay can conveniently be used for the preparation
of amides from carboxylic acids. Various aliphatic and
aromatic carboxylic acids were treated with aliphatic
amines in the presence of the catalyst to prepare different
amides (Table 2). The same catalyst also catalyzed the
reaction of aliphatic carboxylic acids and aniline (and its
derivatives) to form anilides. However, the aromatic
carboxylic acids did not form anilides by reacting with
aromatic amines under similar experimental conditions,
and they remained unchanged. Under the activity of the
catalyst for amide formation at least one of either the
acid or the amine should be aliphatic, but if both are
aromatic, the reaction will not occur. The selectivity of
the amide formation was readily observed by performing
reactions with compounds containing both types of car-
boxylic groups and also by competition experiments
(Table 2). The selectivity is summarized in Chart 1. Also,
in this case, the yields of the amides were found to be
somewhat lower (10-20%) when K-10 montmorillonite
clay was used alone instead of Fe3+-K-10 clay.
Esterification is an important method for the protection
of a carboxylic acid group. The selective esterification of
an aliphatic carboxylic acid in the presence of an aromatic
carboxylic acid is a useful procedure in organic synthesis.
Different methods are known2 for selective esterification
of aliphatic carboxylic acids. All of these methods have
some degree of general applicability, but most of them
are associated with several drawbacks such as complex,
expensive, and hazardous reagents; tedious experimental
procedures; harsh reaction conditions; long conversion
times; and incompatibility with other functions in the
molecules. The catalyst, NiCl2‚6H2O, has recently been
applied2f for selective esterification, but it is applicable
to aliphatic nonconjugated carboxylic acids. 2,2-Dimeth-
ylpropane, MeOH, and a catalytic amount of HCl have
been employed2g only for the preparation of the methyl
esters of aliphatic carboxylic acids. We have also
introduced2h the catalyst, sodium hydrogen sulfate, ad-
sorbed on silica gel (NaHSO4‚SiO2) for the selective
esterification of aliphatic carboxylic acids, but the catalyst
has to be prepared at the time of use. Moreover, the
recovery of the catalyst in the reported methods is also
a problem.
In a continuation of our work on the development of
useful synthetic methodologies,2h,3 we have recently
(1) Part 17 in the series “Studies on Novel Synthetic Methodologies”.
IICT Communication No. 4331.
(2) (a) Bertin, J .; Kagan, H. B.; Luche, J . L.; Setton, R. J . Am. Chem.
Soc. 1974, 96, 8113. (b) Rehn, D.; Ugi, I. J . Chem. Res., Synop. 1977,
119. (c) Banerjee, A.; Sengupta, S.; Adak, M. M.; Banerjee, G. C. J .
Org. Chem. 1983, 48, 3106. (d) Ogaura, T.; Hikasa, T.; Ikegami, T.;
Ono, N.; Suzuki, H. J . Chem. Soc., Perkin Trans. 1 1994, 3473. (e)
Sharma, A.; Chattopadhyay, S.; Mamdapur, V. R. Biotechnol. Lett.
1995, 17, 939. (f) Ram, R. N.; Charles, I. Tetrahedron 1997, 53, 7335.
(g) Rodriguez, A.; Nomen, M.; Spur, B. W.; Godfroid, J . J . Tetrahedron
Lett. 1998, 39, 8563. (h) Das, B.; Venkataiah, B.; Madhusudhan, P.
Synlett 2000, 59.
(3) (a) Das, B.; Madhusudhan, P.; Venkataiah, B. Synlett 1999, 1569.
(b) Das, B.; Venkataiah, B. Synthesis 2000, 1671. (c) Ravindranath,
N.; Ramesh, C.; Das, B. Synlett 2001, 1777. (d) Srinivas, K. V. N. S.;
Reddy, E. B.; Das, B. Synlett 2002, 625.
In conclusion, a simple, highly efficient, and selective
method has been developed for the preparation of esters
(4) Laszlo, P.; Mathy, A. Helv. Chim. Acta 1987, 70, 557.
(5) (a) Barstow, L. E.; Hruby, V. J . J . Org. Chem. 1971, 36, 1305.
(b) Gorecka, A.; Leplawy, M.; Zabrocki, J .; Zwierzak, A. Synthesis 1978,
474. (c) Kubota, T.; Miyashita, S.; Kitazume, T.; Ishikawa, N. J . Org.
Chem. 1980, 45, 5052. (d) Kunieda, T.; Abe, Y.; Higuchi, T.; Hirobe,
M. Tetrahedron Lett. 1981, 22, 1257. (e) Trapani, G.; Reho, A.; Latrofa,
A. Synthesis 1983, 1013.
10.1021/jo0204202 CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/07/2003
J . Org. Chem. 2003, 68, 1165-1167
1165

TABLE 1. P r ep a r a tion of Ester s Usin g F e3+-K-10 Mon tm or illon ite Cla y a s th e Ca ta lyst
yield (%)a
entry
acid
alcohol
CH3OH
CH3CH2OH
CH3OH
CH3CH2OH
(CH3)2CHOH
CH3OH
CH3CH2OH
CH3OH
time (h)
A
B
ref
1
2
3
4
5
6
7
8
C6H5CH2CO2H
C6H5CH2CO2H
7
7
7.5
7.5
8
7
7.5
8
8.5
8
9
7
7.5
8
8.5
8
8.5
9
9.5
7
8
7.5
8
7
96
93
94
91
90
94
92
6a,b
6a,b
6a,c
6a,c
6a
4-(OH)C6H4CH2CO2H
4-(OH)C6H4CH2CO2H
4-(OH)C6H4CH2CO2H
3,4-(CH3O)2C6H3CH2CO2H
3,4-(CH3O)2C6H3CH2CO2H
C6H5CO2H
6d
6c,d
0
0
0
9
4-(OH)C6H4CO2H
3-(Cl)C6H4CO2H
C6H5CH2CO2H
CH3COCO2H
CH3(CH2)16CO2H
CH3(CH2)16CO2H
CH3(CH2)16CO2H
CH3OH
CH3OH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
C6H5CH2OH
C6H5CH2OH
CH3OH
CH3CH2OH
(CH3)2CHOH
CH3OH
CH3CH2OH
CH3OH
CH3CH2OH
CH3OH
CH3CH2OH
CH3OH
CH3CH2OH
CH3OH
CH3OH
CH3CH2OH
84
86
94
92
89
92
87
76
72
94
93
95
93
94
92
91
6a
6a
6a,b
6a,b
6e
6b,e
6b
6a,b
6a,b
6a
6a
6a
6a
6a,b
6a,b
6c,d
CH3(CH2)7CHdCH(CH2)7CO2H
CH3(CH2)7CHdCH(CH2)7CO2H
C6H5CHdCHCO2H
C6H5CHdCHCO2H
2-(CO2H)C6H4CH2CO2H
2-(CO2H)C6H4CH2CO2H
2-(CO2H)C6H4CH2CH2CO2H
2-(CO2H)C6H4CH2CH2CO2H
C6H5CH2CO2H and C6H5CO2H
C6H5CH2CO2H and 3-(Cl)C6H4CO2H
3,4-(CH3O)2C6H3CH2CO2H and C6H5CO2H
0
0
0
0
0
0
0
7.5
8
a
Calculated on the basis of the amount of the isolated product. A: Ester derived from an aliphatic carboxylic acid group. B: Ester
derived from an aromatic carboxylic acid group.
TABLE 2. P r ep a r a tion of Am id es Usin g F e3+-K-10 Mon tm or illon ite Cla y a s th e Ca ta lyst
yield (%)a
entry
acid
amine
time (h)
A
B
ref
7a
7b
7c
7d
1
2
3
4
5
6
7
8
C6H5CH2CO2H
C6H5CH2CO2H
C6H5CH2CO2H
C6H5NH2
7
97
95
92
93
91
95
93
92
4-(CH3O)C6H4NH2
4-(Cl)C6H4NH2
7.5
7.0
8
7.5
8
8.5
9
8
8.5
7
7.5
8
8
9
8
8.5
8
8
8
8.5
9
7
7
8.5
7
4-(OH)C6H4CH2CO2H
4-(OH)C6H4CH2CO2H
3,4-(CH3O)2C6H3CH2CO2H
C6H5CH2CO2H
3,4-(CH3O)2C6H3CH2CO2H
C6H5CO2H
C6H5NH2
4-(CH3O)C6H4NH2
4-(CH3O)C6H4NH2
C6H5NHCH3
7e
7f
7e
C6H5NHCH3
C6H5NH2
C6H5NH2
C6H5CH2NH2
9
0
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
4-(OH)C6H4CO2H
C6H5CO2H
C6H5CO2H
C6H5CO2H
95
93
92
87
78
95
89
92
93
91
90
88
95
93
93
94
92
93
7a,g
7h
7a,i
7a
7a
7a
4-(CH3O)C6H4CH2NH2
C6H5CH2CH2NH2
C6H5CH2NH2
CH3CH2CO2H
C6H5CHdCHCO2H
C6H5CH2CO2H and C6H5CO2H
4-(OH)C6H5CH2CO2H and C6H5CO2H
3,4-(CH3O)2C6H3CH2CO2H and C6H5CO2H
C6H5CO2H
C6H5NH2
C6H5NH2
0
0
0
0
0
4-(CH3O)C6H4NH2
4-(CH3O)C6H4NH2
C6H5NH2 and C6H5CH2NH2
C6H5NH2 and 4-(CH3O)C6H4CH2NH2
C6H5NH2 and C6H5CH2CH2NH2
C6H5NH2
7e
7a,g
7h
C6H5CO2H
3,4-(CH3O)2C6H3CH2CO2H
2-(CO2H)C6H4CH2CH2CO2H
C6H5CH2CO2H
7j,k
0
C6H5CH2NH2
7a,l
7m
7a,l
7n
7k
7e
C6H5CH2CO2H
C6H5CH2CO2H
4-(CH3O)C6H4CH2NH2
C6H5CH2CH2NH2
C6H5CH2NH2
C6H5CH2CH2NH2
4-(CH3O)C6H4CH2NH2
3,4-(CH3O)2C6H3CH2CO2H
3,4-(CH3O)2C6H3CH2CO2H
3,4-(CH3O)2C6H3CH2CO2H
7.5
8
a
Calculated on the basis of the amount of the isolated product. A: Amide derived from an aliphatic or aromatic carboxylic acid group
and an aliphatic amine or from an aliphatic carboxylic acid group and an aromatic amine. B: Amide derived from an aromatic carboxylic
acid group and an aromatic amine.
and amides by using an inexpensive, nonhazardous, and
easily available catalyst. Both conjugated and noncon-
jugated aliphatic carboxylic acids formed the esters in
the presence of aromatic carboxylic acids. The catalyst
was successfully applied for the one-step conversion of
the aliphatic as well as aromatic acids into the corre-
sponding amides by treatment with aliphatic amines.
However, only the aliphatic carboxylic acids (and not the
1166 J . Org. Chem., Vol. 68, No. 3, 2003

gel using hexane-EtOAc (4:1) as the eluent to afford pure ethyl-
2-carboxyphenyl propionate (178 mg, 92%; Table 1, entry 23).
IR (KBr): 3080, 1720, 1692, 1598 cm-1. 1H NMR (CDCl3): δ 8.10
(1H, d, J ) 8.0 Hz), 7.52-7.26 (3H, m), 4.11 (2H, q, J ) 7.0 Hz),
3.35 (2H, t, J ) 7.0 Hz), 2.68 (2H, t, J ) 7.0 Hz), 1.22 (3H, t, J
) 7.0 Hz). MS (m/z): 204 (M•+ - H2O). Anal. Calcd for C12H14O4:
C, 64.86; H, 6.30. Found: C, 64.94; H, 6.28.
CHART 1. Selectivity of Am id e F or m a tion
The spectral and analytical data of the other two representa-
tive esters are given below.
Isop r op yl-4-h yd r oxyp h en yla ceta te (Ta ble 1, En tr y 5). IR
(KBr): 3458, 1726, 1684, 1592 cm-1 1H NMR (CDCl3): δ 7.12
.
(2H, d, J ) 8.0 Hz), 6.75 (2H, d, J ) 8.0 Hz), 6.25 (1H, brs), 5.10
(1H, m), 3.55 (2H, s), 1.32 (6H, d, J ) 7.0 Hz). MS (m/z): 194
(M•+). Anal. Calcd for C11H14O3: C, 68.04; H, 7.22. Found: C,
68.22; H, 7.36.
aromatic carboxylic acids) yielded the anilides by reacting
with aniline and its derivatives. The yields of the esters
and amides are high. For the preparation of the esters
both the primary and secondary alcohols and for prepa-
ration of the amides both the primary and secondary
amines can be used. All the prepared esters are known
compounds,6 while among the amides two compounds
(Table 2, entries 5, 17, and 22) are new.7 The experimen-
tal procedure of the present method is very simple. The
greatest advantage is that the catalyst can be recovered
and reused. The developed method can be applied for the
separation of aromatic carboxylic acids from a mixture
containing aliphatic carboxylic acids and of aromatic
amines from a mixture containing aliphatic amines. We
feel the present process will find important applications
in synthetic organic chemistry.
Ben zyl P yr u va te (Ta ble 1, En tr y 12). IR (neat): 1736,
1652, 1543 cm-1 1H NMR (CDCl3): δ 7.42-7.26 (5H, m), 5.24
.
(2H, s), 2.45 (3H, s). MS (m/z): 178 (M•+). Anal. Calcd for
C10H10O3: C, 67.41; H, 5.62. Found: C, 67.64; H, 5.84.
(B) P r ep a r a tion of Am id e. To a solution of phenylacetic acid
(136 mg, 1 mmol) and aniline (93 mg, 1 mmol) in CHCl3 (10
mL) was added Fe3+-K-10 montmorillonite clay (100 mg). The
mixture was refluxed for 7 h under an N2 atmosphere, cooled,
and filtered. The concentrated filtrate was subjected to column
chromatography over silica gel using hexane-EtOAc (3:2) as the
eluent to obtain pure phenyl acetanilide (N,2-diphenylacetamide;
204 mg, 97%; Table 2, entry 1). IR (KBr): 3447, 3031, 1645, 1600,
1547, 1496 cm-1. 1H NMR (CDCl3): δ 7.18-7.28 (5H, m), 6.98-
7.04 (2H, m), 6.48-6.62 (3H, m), 6.78 (1H, brs), 3.52 (2H, s).
MS (m/z): 211 (M•+). Anal. Calcd for C14H13NO: C, 79.62; H, 6.16;
N, 6.63. Found: C, 79.84; H, 6.18; N, 6.72.
The spectral and analytical data of the unknown amides
(Table 2, entries 5, 17, and 22) and the other two representative
amides are given below.
N-(4-Methoxyphenyl)-2-(4-hydroxyphenyl)acetamide (Table
2, En tr ies 5 a n d 17). IR (KBr): 3291, 1651, 1596, 1514, 1468
cm-1. 1H NMR (CDCl3 + DMSO-d6): δ 7.20 (2H, d, J ) 8.0 Hz),
6.82 (2H, d, J ) 8.0 Hz), 6.64 (2H, d, J ) 8.0 Hz), 6.56 (2H, d,
J ) 8.0 Hz), 6.12 (1H, brs), 3.78 (3H, s), 3.46 (2H, s). MS (m/z):
257 (M•+). Anal. Calcd for C15H15NO3: C, 70.04; H, 5.84; N, 5.45.
Found: C, 70.12; H, 5.78; N, 5.41.
Exp er im en ta l Section
Gen er a l Rem a r k s. All the acids and amines were available
commercially. K-10 montmorillonite clay was obtained from
Fluka Chemicals.
Typ ica l E xp er im en t a l P r oced u r e. (A) P r ep a r a t ion of
Ester . To a solution of 2-carboxyphenyl propanoic acid (194 mg,
1 mmol) in EtOH (10 mL) was added Fe3+-K-10 montmorillonite
clay (100 mg, prepared by reported method4). The mixture was
refluxed for 8 h and cooled. After filtration, the filtrate was
concentrated and purified by column chromatography over silica
N-Ben zylben za m id e (Ta ble 2, En tr y 11). IR (KBr): 3412,
3032, 1631, 1523, 1456 cm-1 1H NMR (CDCl3 + DMSO-d6): δ
.
7.82-7.96 (2H, m), 7.18-7.42 (8H, m), 6.44 (1H, brs), 3.98 (2H,
s). MS (m/z): 211 (M•+). Anal. Calcd for C14H13NO: C, 79.62; H,
6.16; N, 6.63. Found: C, 79.88; H, 6.22; N, 6.77.
(6) (a) Das, B.; Venkataiah, B.; Madhusudhan, P. Synlett 2000, 59.
(b) Commercially available, Aldrich Chemicals. (c) Commercially
available, Lancaster Chemicals. (d) Desmaele, D. Tetrahedron Lett.
1996, 37, 1233. (e) Ramalinga, K.; Vijayalakshmi, P.; Kaimal, T. N. B.
Tetrahedron Lett. 2002, 43, 879.
N-P h en yl-3-(2-ca r b oxyp h en yl)p r op ion a m id e (Ta b le 2,
En tr y 22). IR (KBr): 3375, 3222, 1724, 1631, 1543, 1440 cm-1
.
(7) (a) Buch Staller, H.-P.; Ebert, H. M.; Anlauf, U. Synth. Commun.
2001, 31, 1001. (b) Gazit, A.; App, H.; McMahon, G.; Chen, J .; Lavitzki,
A.; Bohner, F. D. J . Med. Chem. 1996, 39, 2170. (c) Vidya, J .; Sarma,
R. K. J . Indian Chem. Soc. 1988, 65, 564. (d) Ramanarayan, S. R.;
Mona, A. M.; Ahmed, S. M.; Abraham, D. J . J . Med. Chem. 1991, 34,
752. (e) Commercially available, Exploratory Laboratories. (f) Wakita,
Y.; Kobayashi, T.; Maeda, M.; Kojima, M. Chem. Pharm. Bull. 1982,
30, 3395. (g) Commercially available, Aldrich Chemicals. (h) Sampath
Kumar, H. M.; Subba Reddy, B. V.; Anjaneyulu, S.; J agan Reddy, E.;
Yadav, J . S. New. J . Chem. 1999, 23, 955. (i) Laurence, P.; Andre, L.;
Francois, V. Tetrahedron 2002, 58, 2155. (j) Nagarajan, K.; Talwalker,
P. K.; Kulkarni, C. L.; Shah, R. K.; Shenoy, S. J .; Prabhu, S. S. Indian
J . Chem. 1985, 24B, 83. (k) Pridgen, L. N.; Killmer, L. B.; Leewebb,
R. J . Org. Chem. 1982, 47, 1985. (l) Thomas, J . B.; Fall, M. J .; Cooper,
J . B.; Burgess, J . P.; Carroll, I. F. Tetrahedron Lett. 1997, 38, 5099.
(m) Cabaret, D.; Gonzalez, G. M.; Walkselmen, M.; Adediran, S. A.;
Pratt, R. F. Eur. J . Org. Chem. 2001, 141. (n) Vazquez-Tato, P. M.
Synlett 1993, 506.
1H NMR (CDCl3 + DMSO-d6): δ 7.98 (1H, d, J ) 8.0 Hz), 7.40-
6.74 (8H, m), 5.87 (1H, brs), 2.98 (2H, t, J ) 7.0 Hz), 2.64 (2H,
t, J ) 7.0 Hz). MS (m/z): 269 (M•+). Anal. Calcd for C16H15NO3:
C, 71.37; H, 5.57; N, 5.20. Found: C, 71.42; H, 5.51; N, 5.24.
N-Ben zyl-2-(3,4-d im eth oxyp h en yl)a ceta m id e (Ta ble 2,
En tr y 26). IR (KBr): 3398, 1638, 1513, 1452, 1230, 1150 cm-1
.
1H NMR (CDCl3 + DMSO-d6): δ 7.30 (5H, s), 6.79 (1H, s), 6.69
(2H, s), 6.54 (1H, brs), 3.78 (6H, s), 3.69 (2H, s), 3.29 (2H, s).
MS (m/z): 285 (M•+). Anal. Calcd for C17H19NO3: C, 71.57; H,
6.66; N, 4.91. Found: C, 7.64; H, 6.82; N, 4.87.
Ack n ow led gm en t. The authors thank CSIR, New
Delhi, for financial assistance.
J O0204202
J . Org. Chem, Vol. 68, No. 3, 2003 1167