Metal acetate/metal oxide in acetic acid: An efficient reagent for the chemoselective N-acetylation of amines under green conditions

Article abstract of DOI:10.3184/030823410X12746305905926

The use of catalytic amount of metal acetate or metal oxide in acetic acid is a new and highly efficient acetylating system for chemoselective N-acetylation of primary and secondary amines in excellent yields under reflux condition. No other solvent is required. The noted features of this method include mild reaction conditions, use of innocuous reagents, excellent yields, convenient work-up, and reuse of catalyst.

Full text of DOI:10.3184/030823410X12746305905926

288 RESEARCH PAPER
MAY, 288–295
JOURNAL OF CHEMICAL RESEARCH 2010
Metal acetate/metal oxide in acetic acid: an efficient reagent for the
chemoselective N-acetylation of amines under green conditions
Goutam Brahmachari*, Sujay Laskar and Sajal Sarkar
Laboratory of Organic Synthesis and Natural Products, Department of Chemistry, Visva-Bharati University, Santiniketan-731 235,
West Bengal, India
The use of catalytic amount of metal acetate or metal oxide in acetic acid is a new and highly efficient acetylating
system for chemoselective N-acetylation of primary and secondary amines in excellent yields under reflux condition.
No other solvent is required. The noted features of this method include mild reaction conditions, use of innocuous
reagents, excellent yields, convenient work-up, and reuse of catalyst.
Keywords: amines, N-acetylation; chemoselectivity, metal acetates, metal oxides, acetic acid
N-Acetylation of an amino group is one of the most fundamen-
tal as well as useful transformations in organic chemistry.1,2
Because of their nucleophilic and basic character, amines
must be blocked with a protecting group during a multi-step
synthesis, e.g. in the synthesis of a diverse array of biological
molecules such as amino acids, peptides, amino glycosides,
β-lactams, nucleosides and alkaloids. Hence, selective pro-
tection of amino group through acetylation finds immense
significance in organic synthesis. The acetylation of amines
is usually performed employing acid anhydride or acetyl
chloride in the presence of stoichiometric amount of an amine
base, such as triethylamine or pyridine along with 4-
(dimethylamino)pyridine (DMAP), which acts as a co-
catalyst, or 4-pyrrolidinopyridine (PPY).3 Sometimes tribu-
tylphosphine (Bu3P) is also employed as a less basic catalyst
for acylation reactions, particularly for the base sensitive sub-
strates.4,5 Exhaustive literature survey reveals the applications
of a variety of other catalysts also; these include 4-dialkylami-
nopyridine,3 basic alumina,6 perchloric acid adsorbed on silica
gel,7 In(OTf)3,8 ruthenium(III)chloride,9 montmorillonite K-10
and KSF,10 (pyridine)(tetrahydroborato)zinc complex,11 sodium
dodecyl sulfate (SDS),12 acetonyltriphenylphosphonium bro-
mide,13 and many others.14–19 A number of alternative methods
have also been reported for N-acetylation of primary and
secondary amines, where a variety of acetylating agents other
than the conventional acetic anhydride, such as ethyl trifluoro-
acetate,20 ortho-substituted N,N-diacetylaniline,21 dichlorotri-
phenylphosphorane in chloroform,22 imidoylbenzotriazoles,23
poly(3-acyl-2-oxazolone),24 2-acyl-4,5-dichloropyridazine-3-
one,25 N,N-dialkylformamide dimethyl acetal with primary
amides,26 N-acetyl-N-acyl-3-aminoquinazolinones,27 N-methoxy-
diacetamide,28 N-acyl-N-(2,3,4,5,6-pentafluorophenyl)methan
esulphonamides,29 and many others were used.30–32 In spite
of such developments, acetic anhydride (or acetyl chloride) is
still regarded as the key N-acetylating agent, both in com-
mercial and non-commercial sectors. However, both of these
reagents, being corrosive and a lachrymator respectively are
not always ideal.
side reactions (rearrangement, dehydration, etc.) with acid-
sensitive substrates requiring the use of a large excess of acetic
anhydride and low temperature; the reagents are expensive and
some of them are difficult to handle.34–40 Bis(cyclopentadienyl)
zirconium dichloride was found to be a good catalyst,41 but
was used with acetic anhydride and the reaction was not a che-
moselective one; similarly with acetonyltriphenylphospho-
nium bromide (ATPB).42 Kulkarni et al.43 reported the use of
zeolite catalysed acetylation with acetic acid under microwave
irradiation, but this method is not also chemoselective; the
reagent acetylates both alcohols and amines. However, there
are two recent separate reports on the chemoselective acetyla-
tion of amines, alcohols and phenols, but both of the methods
involve the use of acetic anhydride/acetyl chloride as the
acetylating agent in the presence of catalysts.44,45
Although there are numerous methods known for the con-
version of amines into N-acetylated products in good yields,
there is to the best of our knowledge no report on a reliable
methodology which is at same time environmentally benign
and chemoselective in nature. Hence, there is a demand for a
mild as well as an effective and environmentally benign reagent
applicable for chemoselective N-acetylation reactions for a
wide variety of amine substrates. In general, most of the acetyl
transfer reagents are expensive and are obtained by acetylation
with acetylating agents making them unsuitable for large-scale
reactions. Some of these reagents and catalysts lead to waste
and some reactions involve organic solvents, often toxic and
polluting, both unacceptable in these environmentally con-
scious days. A crucial factor for green chemical processes
involves the choice of cheap, safe, efficient and nontoxic
reagents. In continuation of our work on the development of
green methodologies for carbon–heteroatom bond-forming
reactions,46 we have now developed a novel and environmen-
tally benign alternative method for chemoselective N-acetyla-
tion of amines; here we report that metal acetate(s) or metal
oxide(s) in acetic acid act as useful reagents for chemoselec-
tive N-acetylation of structurally diverse amines under reflux
condition (Scheme 1). Metal acetates or metal oxides used in
this reaction act as precatalysts; the process is highly efficient,
cost-effective and environmentally safe with excellent yields.
No other solvent is required for carrying out the reaction. This
alternative method for N-acetylation of amines avoids the use
of conventional acetylating agents (acetyl chloride or acetic
anhydride) and amine additives, and employs instead a cata-
lytic (and reusable) amount of a metal acetate/metal oxide in
acetic acid without the addition of any more solvent. We have
also found for the first time that metal acetate (e.g. zinc acetate,
a benign and inexpensive chemical) alone can act as a selective
N-acetylating agent in the absence of acetic acid with
moderate yields (Table 3).
Thorough inspection into all these reported methods reveals
that although they have certain advantages, they also bear
many drawbacks; such advantages and disadvantages were
extensively described recently by Katritzky.33 The major draw-
backs in some of the above described methods include harsh
reaction conditions, use of hazardous materials, use of excess
acetylating agent and scope for possible side reactions with
acid-sensitive substrates. Pyridine derivatives, such as DMAP
and PPY are highly toxic, while tributylphosphine (Bu3P) is
flammable and air sensitive. Metal triflates lead to potential
For this present protocol, six metal acetates CH3COONa,
Ca(CH3COO)2, Mg(CH3COO)2.4H2O, Mn(CH3COO)2.4H2O,
* Correspondent. E-mail: brahmg2001@yahoo.co.in; brahmg2001@
gmail.com

JOURNAL OF CHEMICAL RESEARCH 2010 289
Scheme 1 Chemoselective N-acetylation of amines.
Cu(CH3COO)2.H2O and Zn(CH3COO)2.2H2O, and five metal
oxides such as MgO, CaO, Al2O3, Cr2O3 and ZnO were used as
precatalysts; all these chemicals are cheap, readily available
and environmentally safe [Pd(CH3COO)2 was also found as a
useful precatalyst for this reaction but was studied in two cases
only because it is a costly chemical]. A variety of structurally
diverse amines (as shown in Table 1) were screened for the
present type of reaction; treatment of the substrates with acetic
acid separately in the presence of catalytic amount of each
of the metal acetates, and each of the metal oxides at reflux
temperature afforded the corresponding N-acetyl derivatives
in excellent yields. No other solvent was required for smooth
running of the reaction. The results of the selective N-acetyla-
tion of amines using a catalytic amount of metal acetates
and also of metal oxides in acetic acid (Scheme 1) are shown
in Table 1 and Table 2, respectively; the overall observations
amply demonstrate the generality and scope of the reaction
with regard to structurally diverse amines. The reaction course
was monitored by thin layer chromatography (TLC) and IR
spectra. The work-up and isolation of the acetylated products
were easy; in most of the cases a chromatographic technique
for isolation of the products was not required. All the acety-
lated products were characterised on the basis of elemental
analyses and physical as well as spectroscopic properties;
For better understanding of the role of metal acetate in this
present reaction, we studied whether such acetylation of
amines could be carried out using a metal acetate only, in the
absence of acetic acid or any other solvent; we have chosen
zinc acetate for this purpose. A mixture of amine and zinc
acetate (1:1 mol ratio) in finely ground form was placed in a
properly sealed container, and heated in an oil-bath (see Exper-
imental). The experimental results revealed that zinc acetate
alone is capable of carrying out the desired transformation;
a number of amino compounds were converted into the corre-
sponding N-acetyl derivatives retaining the chemoselectivity
intact with moderate yields. The reaction course and yields of
the products are summarised in Table 3.
Thus, zinc acetate can act as an acetylating agent for selec-
tive N-acetylation of amines. From the reaction course, we
assume that the relatively more nucleophilic amino group
within the substrate molecules makes a nucleophilic attack
at the metal-bound carbonyl carbon (Scheme 2) resulting the
corresponding N-acetyl derivative and zinc oxide. This mecha-
nism was supported by the isolation of zinc oxide from the
resulting reaction mixture.
It has earlier been mentioned that a catalytic amount of
metal acetate in acetic acid is sufficient enough to bring out the
conversion. Now, we are interested to look into the exact role
of metal acetate in the presence of acetic acid under the reac-
tion condition. For this purpose also, zinc acetate was selected.
Interestingly, on completion of the reaction (with aniline) we
isolated the product along with zinc acetate derivative from the
reaction mixture, and this recovered metal acetate derivative
can successfully be reused for carrying out the transformation
(for three times; Table 4). As per Scheme 2, metal acetate (e.g.
zinc acetate) is converted into a metal oxide (e.g. zinc oxide)
during reaction; but in the presence of acetic acid, it is the
metal acetate that is isolated. Hence, we may assume that the
metal oxide, formed initially, is converted into a metal acetate
derivative in the presence of excess acetic acid under the reac-
tion conditions; consequently, a minute amount of metal ace-
tate is sufficient enough to carry on the reaction following a
catalytic cycle. If this assumption is correct, then a metal oxide
in the presence of acetic acid can also act as an acetylating
system. Such presumption motivated us to carry out the reac-
tion with amines in the presence of a catalytic amount of zinc
oxide in acetic acid; the experimental observations (Table 2)
revealed that the reaction course is almost comparable to that
with zinc acetate in the acetic acid system (Table 1). Success-
ful chemoselective N-acetylation of amines was also achieved
under this metal oxide/acetic acid system (Table 2). During
isolation of the acetylated products, we also recovered zinc
acetate instead of zinc oxide from the resulting reaction mix-
ture, which can be reused. Thus, it may be concluded that the
metal oxide is definitely converted to the metal acetate in
the presence of acetic acid under the reaction condition as per
our mechanistic assumption. To establish the generality of the
reaction, we used six metal acetates as well as five metal oxides
as pre-catalysts (Tables 1 and 2). We also carried out control
experiments with a variety of amines by refluxing them in
acetic acid in the absence of any metal salt – in all these cases
1
the observed melting points/boiling points, IR and H NMR
spectral data were in full agreement with the values reported
for authentic samples, and also with those reported in the
literature (as referred to in Table 1).
The present method is very simple in nature involving no
drastic reaction conditions; the reagents used are also not haz-
ardous and toxic. As shown in Table 1, the process affords
excellent yields within a reasonable reaction time-frame; the
newly developed methodology is not only efficient and envi-
ronmentally benign, but also offers a cheap as well as a readily
available acetylating agent. Hence, our present methodology is
anticipated to draw attention for its immense application in
large scale production as well. In most of the cases, the reac-
tion was completed within 0.25–4.5 h with more than 90% of
yield. The reaction is applicable to both aromatic and aliphatic
amines; the most fascinating feature of this present reaction
scheme is its chemoselectivity — the process is selective for
amines in the presence of alcohols (both aliphatic and aro-
matic), thiols, and also tolerant of some other functionality
as evidenced from the experimental results shown in Table 1.
The aminoalcohols and aminophenols (entries 17,18,38–40)
underwent smooth acetylation under the reaction procedure
only at the amino group. Like hydroxy groups, thiols did not
get acetylated under the reaction condition (entries 14–16).
Amino-acetic acid (glycine), a natural aminoacid, was also
found to be acylated effectively at the amino group following
this procedure (entry 19). In one case (entry 30), this reaction
was also applied to a hydrazine substrate successfully with
N-acetylation only at the primary amino group; thus for hydra-
zine derivatives where both 10- and 20-amino groups are pres-
ent, it appears that it is only the 10- amino group that will
undergo acetylation under this reaction. This is also a notable
feature of this present procedure.

290 JOURNAL OF CHEMICAL RESEARCH 2010
N
N
N
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N
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N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
n
n
o
p

JOURNAL OF CHEMICAL RESEARCH 2010 291
N
N
N
N
N
N
N
,
N
N
N
Ctoinued

292 JOURNAL OF CHEMICAL RESEARCH 2010
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JOURNAL OF CHEMICAL RESEARCH 2010 293
Table 3 N-Acetylation of amines with zinc acetate without
anhydrous sodium sulfate and the solvents were removed in a rotary
evaporator under reduced pressure. Reactions were monitored by TLC
on silica-gel 60 F254 (Merck). A water condenser having a CaCl2
guard-tube was used for refluxing the reaction mixture. A sealed tube
(15 mL) from Tensil Pvt. Ltd was used in solid phase reactions.
acetic acid
Entry
Amines
Time/h
% Yielda
1
2
n-Propylamine
2.75
3.0
3.0
3.15
3.0
3.5
3.5
3
58
60
60
60
66
62
68
64
54
53
61
63
62
69
Aniline
3
1-Phenylethylamine
4-Aminobenzenethiol
2-Aminoethanol
1-(4-Aminophenyl)ethanol
Aminoacetic acid
p-Tolylamine
2-Chlorophenylamine
4-Chlorophenylamine
4-Bromophenylamine
1-(4-Aminophenyl)-ethanone
4-Aminobenzoic acid
3-Nitrophenylamine
Caution: 2-Naphthylamine (β-naphthylamine, naphthalene-
2-amine) is a known potent human carcinogen. In the United
Kingdom it appears in Schedule 2 of the Control of Sub-
stances Hazardous to Health Regulations (COSSH) 1999
which prohibits its “manufacture and use for all purposes”.
4
5
6
7
8
9
3.5
1.5
3
10
11
12
13
14
Acetylation of amines using metal acetates as precatalysts; general
procedure
4
To a mixture of CH3COOH (1.2 mL) and metal acetate (0.25 mmol),
an amine (1 mmol) was added and then the reaction mixture was
refluxed with gentle heating for a length of time as indicated in
Table 1. The progress of the reaction was monitored by TLC. After the
reaction was complete, CH2Cl2 or EtOAc was added to the reaction
mixture, and the metal acetate was removed by filtration. The organic
solution was then washed with a saturated solution of NaHCO3 and
also with H2O (2 × 10 mL), and then dried over anhydrous Na2SO4.
After removal of the solvent (in a rotary evaporator under reduced
pressure), the product was obtained; it was then purified by recrystal-
lisation with a suitable solvent. Column chromatographic techniques
were used to purify the product whenever required. The structure of
the products was confirmed by physical and spectral studies (IR and
1H NMR) in addition to comparison with authentic samples obtained
commercially or prepared by reported methods.
4
4
a Yields are of pure isolated products characterised by their
physical constants, spectroscopic characteristics (FT-IR, 1H
NMR) as compared with those of authentic samples (commer-
cially available or prepared as per reported methods) as well as
with reported values in the literature.
the reactions were found to be unsatisfactory; minor amounts
of conversion are observed only after prolonged heating (see
Experimental).
In conclusion, we have demonstrated metal acetate or metal
oxide in acetic acid as a novel and highly efficient acetylating
system for the chemoselective N-acetylation of primary and
secondary amines in excellent yields at reflux temperature; it
has also been shown that metal acetate alone can act as a selec-
tive N-acetylating agent in the absence of acetic acid. To
the best of our knowledge, this is the first report on chemose-
lective N-acetylation of all types of amines under green condi-
tions. This newly developed chemoselective procedure for the
N-acetylation of a wide variety of structurally diverse amines
by the use of a catalytic amount of metal acetate or metal oxide
(as pre-catalyst) in acetic acid represents a tremendous oppor-
tunity for the practice of green chemistry. The major advan-
tages of this environmentally benign and safe protocol include
a simple reaction setup, mild reaction condition, high effi-
ciency, moderate reaction times, the possibility for reusing the
catalyst, chemoselectivity, and obviously use of innocuous,
cost-effective and readily available reagents. Hence, we are
optimistic that this present methodology as a whole would find
itself as a useful alternative for large scale production in the
future.
Alternative procedure
To a mixture of CH3COOH (1.2 mL) and metal acetate (0.25 mmol)
was added an amine (1 mmol) and then the reaction mixture was
refluxed with gentle heating for the length of time indicated in
Table 1. The progress of the reaction was monitored by TLC. After the
reaction was complete, the reaction mixture was added in 20 mL ice
cold water with vigorous stirring. The acetylated product precipitated
within 5-10 min. The precipitated product was filtered, washed with
water (2 × 10 mL), dried by pressing between folds of filter paper and
finally dried in a vacuum desiccator. In cases where the product did
not precipitate, the reaction mixture was extracted with ethyl acetate
(2 × 25 mL). The organic solvent was then washed with a saturated
solution of NaHCO3 and also with H2O (2 × 10 mL), and after then
dried over anhydrous Na2SO4. After removal of the solvent under
reduced pressure, the product was obtained with almost identical
yields as recorded for the earlier procedure; it was then purified by
recrystallisation with a suitable solvent. A column chromatographic
technique was used to purify the product whenever required.
The structure of the products was confirmed by physical and spectral
1
studies (IR and H NMR) in addition to comparison with authentic
samples obtained commercially or prepared by reported methods.
Experimental
General remarks
Acetylation of amines using metal oxides as precatalysts; general
procedure
All the reagents and the solvents (analytical grade) as used were pur-
chased from reputed commercial suppliers. All the solvents were dried
before use. IR spectra were recorded in KBr discs on a Shimadzu
8201 PC–IR spectrophotometer. 1H NMR spectra were recorded on a
Bruker DRX-400 NMR spectrometer in CDCl3/acetone-d6 with TMS
as internal reference. Melting points were recorded on a Vego melting
point apparatus and were uncorrected. Column chromatographic
separations were carried out on SRL silica gel (60–120 mesh) using
EtOAc/petroleum ether as eluent. Organic extracts were dried with
To a mixture of CH3COOH (1.2 mL) and metal oxide (0.3 mmol) was
added an amine (1 mmol), and then the reaction mixture was refluxed
with gentle heating for a length of time indicated in Table 2. On com-
pletion of the reaction as monitored by TLC, CH2Cl2 or EtOAc was
added to the reaction mixture and metal acetate was removed by filtra-
tion. The organic solvent was then washed with a saturated solution of
NaHCO3 and also with H2O (2 × 10 mL), and after then dried over
anhydrous Na2SO4. After removal of the solvent (with the help of
rotary evaporator under reduced pressure), the product was obtained;
Scheme 2 Nucleophilic attack of amino group at the metal-bound carbonyl carbon.

294 JOURNAL OF CHEMICAL RESEARCH 2010
7
8
9
A.K.Chakraborti and R. Gulhane, Chem. Commun., 2003, 1896.
K.K. Chauhan and C.G. Frost, J. Chem. Soc. Perkin Trans., 2000, 3015.
S.K. De, Tetrahedron Lett., 2004, 45, 2919.
Table 4 Reuse of zinc acetate
10 A. Li, T. Li and T. Ding, Chem. Commun., 1997, 1389.
11 B. Zeynizadeh and K. Zahmatkesh, J. Chin. Chem. Soc., 2004, 51, 801.
12 S. Naik, G. Bhattacharjya, B. Talukdar and B.K. Patel, Euro. J. Org. Chem.,
2004, 1254.
No. of uses
Product yield /% Recovery of zinc acetate /%
13 A.T. Khan, L.H. Choudry and S. Ghosh, Eur. J. Org. Chem., 2005, 2782.
14 P. Saravanan and V.K. Singh, Tetrahedron Lett., 1999, 40, 2611.
15 E.F.V. Scriven, Chem. Soc. Rev., 1983, 12, 129.
16 S.P. Chavan, R. Anand, K. Pasupathy and B.S. Rao, Green Chem., 2001, 3,
320.
1
2
3
96
92
89
98
93
91
17 P. Lidstrom, J. Tierney, B. Wathey and J. Westman, Tetrahedron, 2001, 57,
9225.
18 A.K. Chakraborti, R. Gulhane and Shivani, Synthesis, 2004, 111.
19 A.T. Khan, S. Islam, A. Majee, T. Chattopadhyay and S. Ghosh, J. Mol.
Cat. A, 2005, 239, 158.
it was then purified by recrystallisation with a suitable solvent. A
column chromatographic technique was used to purify the product
whenever required. The structure of the products was confirmed by
physical and spectral studies (IR and H NMR) in addition to com-
parison with authentic samples obtained commercially or prepared by
reported methods
1
20 D. Xu, K. Prasad, O. Repic and T.J. Blacklock, Tetrahedron Lett., 1995, 36,
7357.
21 Y. Murakami, K. Kondo, K. Miki, Y. Akiyama, T. Watanabe and Y.
Acetylation of amines with zinc acetate without using acetic acid;
general procedure
Yokoyama, Tetrahedron Lett., 1997, 38, 3751.
22 I. Azumaya, T. Okamoto, F. Imabeppu and H. Takayanagi, Tetrahedron,
2003, 59, 2325.
23 A.R. Katrizky, C. Cai and S.K. Singh, J. Org. Chem., 2006, 71, 3375.
24 T. Kunieda, T. Higuchi,Y. Abe and M. Hirobe, Tetrahedron Lett., 1982, 23,
1159.
25 Y.-J. Kang, H.-A. Chung, J.-J. Kim and Y.-J. Yoon, Synthesis, 2002, 733.
26 T.A. Dineen, M.A. Zajac and A.G. Myers, J. Am. Chem. Soc., 2006, 128,
16406.
27 R.S. Atkinson, E. Barker and M.J. Sutcliffe, Chem. Commun., 1996, 1051.
28 Y. Kikugawa, K. Mitsui, T. Sakamoto, M. Kawase and H. Tamiya,
Tetrahedron Lett., 1990, 31, 243.
29 K. Kondo, E. Sekimoto, J. Nakao andY. Murakami, Tetrahedron, 2000, 56,
5843.
30 M.-J. Kim, W.-H. Kim, K. Han, Y.K. Choi and J. Park, Org. Lett., 2007, 9,
1157.
31 W.-J. Yoo and C.-J. Li, J. Am. Chem. Soc., 2006, 128, 13064.
32 L. Kisfaludy, T. Mohacsi, M. Low and F. Drexler, J. Org. Chem., 1979, 44,
654.
Finely ground amine (1 mmol) and zinc acetate dihydrate (1 mmol)
was placed in a 25 mL tube which was then sealed. This was heated
in an oil bath at 150 °C and stirred with a magnetic stirrer for 3–4 h
(Table 3). On completion of reaction, the sealed tube was cooled
and then the reaction mixture was extracted with EtOAc (2 × 25 mL).
The organic solvent (separated by filtration) was then washed with a
saturated solution of NaHCO3 and also with H2O (2 × 10 mL) and then
dried over anhydrous Na2SO4. After removal of the solvent, the pro-
duct was obtained which was purified by recrystallisation with a
suitable solvent. A column chromatographic technique was used to
purify the product. The structure of each of the products was con-
firmed by IR and 1H NMR spectra as well as by TLC comparison with
authenticated samples.
Control experiment with amines
A mixture of an amine (1 mmol) and CH3COOH (1.2 mL) in the
absence of any metal salt (metal acetate/metal oxide) was refluxed for
a prolonged length of time (14–16 h), and then worked-up following
the same procedure as discussed in earlier sections. The percentage
of isolated yields (obtained after column chromatographic resolution)
of the corresponding N-acetylated products were found to be very
poor in comparison to those obtained in the newly developed method
(Tables 1 and 2). Representative entries : n-propylamine (yield, 16%;
refluxing period, 12 h); N-methylaniline (yield, 19%; refluxing
period, 14 h); p-methoxylaniline (yield, 24%; refluxing period, 12 h);
4-nitroaniline (yield, 21%; refluxing period, 16 h).
33 A.R. Katritzky, H.-Y. He and K. Suzuki, J. Org. Chem., 2000, 65, 8210.
34 K. Ishihara, M. Kubota, H. Kurihara and H. Yamamoto, J. Org. Chem.,
1996, 61, 4560.
35 P.A. Procopiou, S.P.D. Baugh, S.S. Flack and G.G.A. Inglis, J. Org. Chem.,
1998, 63, 2342.
36 K.K. Chauhan, C.G. Frost, I. Love and D. Waite, Synlett., 1999, 1743.
37 P. Saravanan and V.K. Singh, Tetrahedron Lett., 1999, 40, 2611.
38 K.L.Chandra, P. Saravanan, R.K. Singh and V.K. Singh, Tetrahedron, 2002,
58, 1369.
39 R. Dalpozzo, A.D. Nino, L. Maiuolo, A. Procopio, M. Nardi, G.I. Bartol
and R. Romeo, Tetrahedron Lett., 2003, 44, 5621.
40 A. Orita, C. Tanahashi, A. Kakuda and J. Otera, Angew. Chem. Int. Ed.,
2000, 39, 2877.
41 M.L. Kantam, K. Aziz and P.R. Likhar, Catal. Commun., 2006, 7, 484.
42 A.T. Khan, L.H. Choudhury and S. Ghosh, Eur. J. Org. Chem., 2005,
2782.
43 K.V.V. Krishna Mohan, N. Narender and S.J. Kulkarni, Green Chem.,
2006, 8, 368.
Reuse of metal acetate
On completion of the reaction with aniline, the reaction mixture was
extracted with ethyl acetate; the metal acetate was filtered off, washed
with dichloromethane, dried for 1 h at 110 °C, and then reused in
another reaction (Table 4).
44 S. Farhadi and M. Zaidi, J. Mol. Catal. A, 2009, 299, 18.
45 B. Das, P. Thirupathi, R.A. Kumar and K. Laxminarayana, Adv. Synth.
Catal., 2007, 349, 2677.
46 G. Brahmachari and S. Laskar, Tetrahedron Lett., 2010, 51, 2319.
47 Dictionary of organic compounds, 4th edn, Chapmann and Hall, London,
1965, Vol. 5, p 2790.
48 B. Das and P. Thirupathi, J. Mol Cat. A., 2007, 269, 12.
49 J.R. Salim, Synth. Commun., 1989, 19, 1181.
50 H. Eshghi, J. Chem. Res., 2004, No. 12, 802.
51 B.S. Furniss, A.J. Hannaford, P.W.G. Smith, A.R. Tatchell, Vogel’s textbook
of practical organic chemistry, 5th edn, Longman: ELBS, 1991, pp. 1370.
52 P.J. Garratt, S. Travard, S. Vonhoff, A. Tsotinis and D. Sugden, J. Med.
Chem., 1996, 39, 1797.
We are thankful to the Bose Institute, Kolkata and CDRI,
Lucknow for spectroscopic measurements. Financial supports
from UGC, New Delhi and also from Visva-Bharati University
are gratefully acknowledged.
Received 21 January 2010; accepted 10 April 2010
Paper 100971 doi: 10.3184/030823410X12746305905926
Published online: 8 June 2010
References
53 F. Tamaddon, M. Khoobi and E. Keshavarz, Tetrahedron Lett., 2007, 48,
3643.
54 P. Salehi and A.R. Motlagh, Syn. Commun., 2000, 30, 671.
55 K. Kondo, E. Sekimoto, J. Nakao andY. Murakami, Tetrahedron, 2000, 56,
5843.
1
T.W. Greene and P.G.M. Wuts, Protective groups in organic synthesis, 3rd
edn, Wiley, New York, 1999, pp.150.
2
L. Pearson, W.J. Roush, Handbook of reagents for organic synthesis:
activating agents and protecting groups, John Wiley and Sons, Chichester,
UK, 1999, pp 9–16.
56 Y. Jiang, Org. Lett., 2009, 11, 5250.
57 R.S. Sengar, New J. Chem., 2003, 27, 1115.
58 H. Wenker, J. Am. Chem Soc., 1935, 57, 1079.
59 S. Nagamine, T. Otawa, H. Nakae and S. Asada, Chem. Pharm. Bull., 1988,
36, 4612.
60 S. Inui and S. Asada, Yakugawa Zasshi, 1987, 107, 904.
61 R. Taylor, G.G. Smith and W.H. Wetzell, J. Am. Chem. Soc., 1962, 84,
4817.
3
G. Hofle, W. Steglich and H. Vorbruggen, Angew. Chem. Int. Ed., 1978, 17,
569.
4
5
E. Vedejs and S.T. Diver, J. Am. Chem. Soc., 1993, 115, 3358.
E. Vedejs, N.S. Bennet, L.M. Conn, S. T. Diver, M. Gingras, S. Lin, P. A.
Oliver and M.J. Peterson, J. Org. Chem., 1993, 58, 7286.
S. Paul, P. Nanda, R. Gutpa and A. Loupy, Tetrahedron Lett., 2002, 43,
4261.
6

JOURNAL OF CHEMICAL RESEARCH 2010 295
62 J. Wettergren, A. Bogevig, M. Portier and H. Adolfsson, Adv. Synth. Catal.,
2006, 348, 1277.
63 Dictionary of organic compounds, 4th edn, Chapmann and Hall, London,
1965, Vol.1, p 21.
64 H. Dakin, J. Biol. Chem., 1929, 82, 439.
65 S.J. Tremont and H.U. Rahman, J. Am. Chem. Soc., 1984, 106, 5759.
66 R. Gupta, V. Kumar, M. Gupta, S. Paul and R. Gupta, Indian J. Chem.,
2008, 47B, 1739.
67 B.T. Gowda, I. Svoboda and H. Fuess, Acta Crystallogr., 2007, E63, 3267
(doi:10.1107/S1600536807028991).
68 G.K. Chip and J.S. Grossert, Can. J. Chem., 1972, 50, 1233.
69 S.C. Bisarya and R. Rao, Synth. Commun., 1993, 23, 779.
70 Dictionary of organic compounds, 5th edn, Chapmann and Hall, London,
1982, Vol. 1, pp 304-305.
71 W.S. Fones, J. Org. Chem., 1949, 14, 1099.
72 M.M. Heravi, F.K. Behbahani, R.H. Shoar and H.A. Oskooie, Cat.
Commun., 2006, 7, 136.
73 B.P. Bandgar, S.P. Kasture and V.T. Kamble, Synth. Commun., 2001, 31,
2255.
74 T. Higuchi and M. Hirobe, Tetrahedron Lett., 1981, 22, 1257.
75 M. Freifelder, J. Org. Chem., 1962, 27, 1092.

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