A facile and efficient method for the selective deacylation of N-arylacetamides and 2-chloro-Narylacetamides catalyzed by SOCl2

Article abstract of DOI:10.1007/s11164-011-0327-6

Thionyl chloride efficiently and selectively promoted the deacylation of N-arylacetamides and 2-chloro-N-arylacetamides, under anhydrous conditions, without effecting the ester group, aminosulfonyl group, or benzyloxyamide group. This method, which has been successfully applied to a variety of substrates including different N-arylacetamides and 2-chloro-N-arylacetamides, has the attractive advantages of inexpensive reagents, satisfactory selectivity, excellent yields, short reaction time, and convenient workup. This new method can probably be used to selectively deacylate between aromatic amides and alkyl amides. Springer Science+Business Media B.V. 2011.

Full text of DOI:10.1007/s11164-011-0327-6

Res Chem Intermed (2012) 38:77–89
DOI 10.1007/s11164-011-0327-6
A facile and efficient method for the selective
deacylation of N-arylacetamides and 2-chloro-N-
arylacetamides catalyzed by SOCl2
•
Gong-Bao Wang Lin-Fa Wang Chao-Zhang Li
•
•
•
Jing Sun Guang-Ming Zhou Da-Cheng Yang
•
Received: 21 January 2011 / Accepted: 15 May 2011 / Published online: 8 June 2011
Ó Springer Science+Business Media B.V. 2011
Abstract Thionyl chloride efficiently and selectively promoted the deacylation of
N-arylacetamides and 2-chloro-N-arylacetamides, under anhydrous conditions,
without effecting the ester group, aminosulfonyl group, or benzyloxyamide group.
This method, which has been successfully applied to a variety of substrates
including different N-arylacetamides and 2-chloro-N-arylacetamides, has the
attractive advantages of inexpensive reagents, satisfactory selectivity, excellent
yields, short reaction time, and convenient workup. This new method can probably
be used to selectively deacylate between aromatic amides and alkyl amides.
Keywords Thionyl chloride Á N-arylacetamides Á 2-chloro-N-arylacetamides Á
Deacylation
Introduction
Amino group protection is of key importance in organic synthesis. Acetylation is
one of the most universal ways of protection of the amino group. The most popular
reagents for acetylation of amino group are CH3COCl and Ac2O, and the acetylated
products are usually obtained in high yields in alkaline media at ambient
temperature.
Various methods have been reported for the deacetylation of aromatic amides,
including:
1. Hydrolysis of the acetyl amino group under basic (NaOH [1–3], KOH [4, 5],
etc.) or acidic (HCl [6, 7], HBr [8], AcOH [9], etc.) conditions;
G.-B. Wang Á L.-F. Wang (&) Á C.-Z. Li Á J. Sun Á G.-M. Zhou Á D.-C. Yang (&)
College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
e-mail: linfa@swu.edu.cn
D.-C. Yang
e-mail: hxydc@swu.edu.cn
123

78
G.-B. Wang et al.
2. Alcoholysis of the acetyl amino group catalyzed by acid (HCl [10]) or alkali
(CH3ONa [11]) in alcohol.
Of the two methods, the first usually requires harsh conditions, for example high
reaction temperature, excessively strong catalysts, or long time. Under such reaction
conditions, the coexisting ester group is usually hydrolyzed more easily than
corresponding amido group. Comparatively, the second method has the advantages
of convenient operation, good yields and shorter reaction time.
Thionyl chloride (SOCl2) is a reactive chemical reagent mainly used in the
industrial production of organochlorine compounds, which are often intermediates
in pharmaceuticals and agrichemicals. It has not been studied as promoter in
deacylation of aryl amides. We report herein a facile and efficient method for
deacylation of N-arylacetamides and 2-chloro-N-arylacetamides catalyzed by
SOCl2. The reactions in shown in Scheme 1.
Results and discussion
To determine the optimum amount of SOCl2 catalyst we initially studied the
reaction of 4-nitroacetanilide (5 mmol) with different amounts of SOCl2 in CH3OH
(13 mL) at room temperature (Scheme 2). It was found that use of less than 0.6
molar ratio of SOCl2 to 4-nitroacetanilide gave a moderate yield of the
corresponding aromatic amine and required a long time (Table 1, entries 1–2),
whereas use of more than 0.8 molar ratio gave an excellent yield in a short time
(Table 1, entries 3–7). Comprehensively taking the amount of SOCl2, reaction time,
and product yields into account, we chose 0.8 as the optimum molar ratio. This
molar ratio is also suitable for other N-arylacetamides.
HN
H2N
ClCH2COCl
K2CO3
Cl
R1
R1
O
3
1
K2CO3
CH3COCl
SOCl2 CH3OH
HN
O
HCl.H2N
SOCl2
R1
R1
CH3OH
2
4
R1= 4-OEt, 4-OMe, 4-Me, H, 3-Br, 4-Br, 4-Cl, 3,4-diCl, 3-Cl-4-F, 2-NO2, 3-NO2, 4-NO2,4-CF3,4-CO2Me,
4-CONHEt, 4CONHOH, 4-SO2NH2, 4-SO2NHMe, 4-(N-(5-methylisoxazol-3-yl)sulfamoyl),
4-(N-(4-(methoxycarbonyl)phenyl)sulfamoyl), and/or 4-(N-pyrimidin-2-ylsulfamoyl).
O
ClCH2COCl
K2CO3
Cl
SOCl2
N
H.HCl
N
H
N
CH3OH
4
1
3
N
N
N
N
N
N
NH
,
N
=
N N
,
,
N
S
Scheme 1 Deacylation of N-arylacetamides and 2-chloro-N-arylacetamides
123

A facile and efficient method
79
NO2
NO2
NO2
O
aq.
K2CO3
H2N
SOCl2
N
H
HCl H2N
Scheme 2 Model reaction
Table 1 Catalytic effect of
SOCl2 on the deacetylation of
4-nitroacetanilide in CH3OH
Entry
SOCl2 (mmol)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
1.0
2.0
3.0
4.0
5.0
6.0
7.0
16
14
5
41.1
83.2
99.1
99.6
99.7
99.8
99.8
2.5
2
Reaction conditions:
4-nitroacetanilide (5.0 mmol),
CH3OH (13.0 mL); 29 °C
1.1
0.7
a
Isolated yield
Table 2 Deacetylation of
4-nitroacetanilide in the
presence of SOCl2 with different
solvents
Entry
Solvent
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
CH2Cl2
CHCl3
12
12
12
12
12
2.3
7
Trace
Trace
Trace
Trace
Trace
99.4
CH3CN
THF
(CH3)2CO
CH3OH
C2H5OH
n-C3H7OH
Reaction conditions:
4-nitroacetanilide (5.0 mmol),
SOCl2 (4.0 mmol), solvent
(13.0 mL); 30 °C
98.7
11.5
99.1
a
Isolated yield
The next work was to evaluate the solvent effect (Table 2). Different solvents, for
example dichloromethane, chloroform, acetonitrile, tetrahydrofuran (THF), acetone,
methanol, ethanol, and propanol, were used for transformation of 4-nitroacetanilide
with SOCl2 at ambient temperature. The experimental results showed that CH3OH
was the best solvent, with the highest yield and shortest reaction time (Table 2,
entry 6). It was also worthy of note that alcohols, for example CH3OH, C2H5OH,
and n-C3H7OH, promoted deacetylation of aromatic amides (Table 2, entries 6–8),
thus deacetylation of the model molecule may be a type of alcoholysis reaction.
We used a variety of catalysts to determine which was the most effective for
deacetylation of 4-nitroacetanilide (5.0 mmol) at room temperature. The results
obtained (Table 3) showed SOCl2 was more efficient than conc. HCl, conc. H2SO4
and conc. HNO3 for deacetylation of 4-nitroacetanilide under these conditions.
Finally the effect of temperature on the reaction was investigated (Table 4).
Selecting the same model reaction, we examined the deacetylation of 4-nitroace-
tanilide (5.0 mmol) with SOCl2 (4.0 mmol) at different temperatures in CH3OH. As
can be seen from Table 4, reaction rate and yield increased as the reaction
123

80
G.-B. Wang et al.
Table 3 Deacetylation of
4-nitroacetanilide in the
presence of different catalysts
with CH3OH as solvent
Entry
Catalyst
Amount
of catalyst
(mmol)
Time (h)
Yielda (%)
1
2
3
4
conc. HCl
conc. H2SO4
conc. HNO3
SOCl2
4.0
4.0
4.0
4.0
9.5
14
51.6
45.3
34.3
99.6
Reaction conditions:
4-nitroacetanilide (5.0 mmol),
CH3OH (13.0 mL), 29 °C
20
2.5
a
Isolated yield
Table 4 Deacetylation of 4-nitroacetanilide in the presence of SOCl2 at different temperatures
Entry
Temp (°)
Time (h)
Yielda (%)
1
2
3
4
29
2.5
1.0
0.4
0.1
99.2
99.1
99.4
99.6
40
50
Reflux
Reaction conditions: 4-nitroacetanilide (5.0 mmol), SOCl2 (4.0 mmol), CH3OH (13.0 mL)
a
Isolated yield
temperature was increased from 29 °C to reflux temperature. Hence reflux
temperature was optimum because of its highest yield and shortest reaction time.
To evaluate the scope of this procedure, the deacetylation of other
N-arylacetamides (Table 5) was also investigated under the optimum reaction
conditions (Table 6). As shown, deacetylation of N-arylacetamides with the aid of
SOCl2 proceeded with excellent yields in CH3OH solution at reflux temperature
(Table 6, entries 1–19). In addition, N-arylacetamides with electron-withdrawing
groups in the aromatic ring (Table 6, entries 5–19) were somewhat more reactive,
with shorter reaction time (all less than 3.0 h) than those with electron-donating
groups (Table 6, entries 1–3, all more than 8.0 h). In particular, deacetylation of
substrates with an NO2 group in the aromatic ring required less than 0.2 h only, with
excellent yields (Table 6, entry 14–15), because of the strong electrophilic effect of
the NO2 group.
To expand the scope of this new method, we explored the deacylation of a variety
of 2-chloro-N-aryl-acetamides (Table 7) in the presence of SOCl2 (Table 8). It was
of interest to note that deacylation of 2-chloro-N-arylacetamides (Table 8, entries 1,
2, 4–7, 9, 10) was completed much more quickly and with much better yields than
deacylation of N-arylacetamides with the same substituent groups in the aromatic
ring (Table 6, entries 2, 3, 6–9, 10, 14). Furthermore, deacylation of 2-chloro-N-aryl
acetamides containing electron-donating groups, for example OCH3, CH3, in the
aromatic ring (Table 8, entries 1, 2) was achieved within 2 h, whereas deacylation
of those with electron-withdrawing groups, for example NO2 (Table 8, entries
10–11), required 0.05 h only. This difference indicated that electrophilic substit-
uents in the aromatic ring has a fundamental effect on the rate of deacylation.
Compared with 2-chloro-N-arylacetamides bearing a benzene ring (Table 8, entries
123

A facile and efficient method
81
Table 5 Preparation of N-arylacetamides
M.p. (°C)
Ref.
[12]
Entry
1
Compound 1a
Product 2b
Time(h) Yieldc(%)
131.2-135.7
(134.4)
11
11
13
11
15
17
13
13
77.2
74.3
96.0
68.0
64.1
66.4
91.9
77.8
EtO
NH2
NH2
NH2
EtO
MeO
Me
NHAc
137.6-139.2
(130-132)
154.4-155.1
(151-154)
118.7-123.2
(114-116)
174.4-178.4
(173-174)
123.1-126.9
(127)
[13]
[14]
[15]
[16]
[17]
[18]
[19]
2
3
4
5
6
7
8
MeO
Me
NHAc
NHAc
NH2
NHAc
Br
NH2
CO2Me
NH2
Br
AcHN
Cl
NHAc
CO2Me
NHAc
NHAc
H2
N
131.5-134.2
(172-174)
161.2-163.0
(153-155)
Cl
F3C
NH2
F3C
Cl
Cl
122.7-127.2
[20]
9
17
89.3
Cl
NH2
Cl
NHAc
NHAc
(121.9-123.3)
O
S
156.4-159.0
(165-166)
O
S
[21]
[22]
[23]
10
11
H2
N
NH2
18
22
80.8
71.9
H2N
O
O
O
S
O
S
160.2-163.5
(220-221)
N
N
O
H
N
H
N
O
NH2
NHAc
O
O
Me
Me
157.5-159.7
(152-153)
O
O
12
13
16
16
72.4
77.6
Me HN
S
NH2
Me HN
S
NHAc
O
O
O
S
O
S
HN
NH2
171.1-172.8
HN
NHAc
O
O
O2
N
O2
N
144.5-145.8
[24]
[25]
14
15
67.8
NH2
NHAc
(147.3-147.5)
215.1-216.5
(215-216)
15
16
15
16
64.2
78.4
O2
N
NH2
O2
N
NHAc
O
O
184.2-186.7
NH2
NHAc
NHAc
Et NH
Et NH
O
O
17
18
16
16
79.0
75.4
175.6-179.5
172.4-175.8
NH2
HO NH
HO NH
O
O
S
CO2Me
CO2Me
H2
N
S
NH
AcHN
NH
O
O
O
S
O
257.4-261.5
(257-258)
N
N
N
[26]
19
HN
NH2
16
73.6
HN
S
NHAc
N
O
O
a
The substrate(4 mmol) was treated with acetyl chloride (24 mmol) in the presence of 24 mmol K2CO3
in acetone at room temperature
b
All products were identified by IR and 1H NMR spectra
c
Yields refer to pure isolated products
123

82
G.-B. Wang et al.
Table 6 SOCl2-catalyzed deacylation of N-arylacetamides
Entry
1
Time(h) Yieldc(%)
M.p. (°C)
Ref.
[27]
Compound 2a
Product 4b
233.3-235.2
(233-234)
NH2.HCl
10.5
10.0
8.0
4.0
3.0
3.0
2.5
2.5
92.9
97.5
91.9
98.5
94.7
98.8
93.1
91.6
EtO
NHAc
NHAc
NHAc
EtO
MeO
Me
186.5-187.4
(185-186)
NH2.HCl
NH2.HCl
2
3
4
5
6
7
8
[28]
[29]
MeO
Me
232.3-235.4
(232-235)
NH2.HCl
196.8-198.9
NHAc
165.2-167.0
(165.5)
NH2.HCl
[30]
[33]
[31]
Br
AcHN
Cl
NHAc
CO2Me
NHAc
NHAc
Br
HCl.H2
Cl
270.1-272.5
(272)
N
CO2Me
249.1-251.3
(253)
NH2.HCl
NH2.HCl
201.2-203.8
F3
C
F3C
Cl
Cl
163.5-164.9
(164)
9
2.5
96.1
[32]
[34]
Cl
NHAc
NHAc
Cl
NH2.HCl
NH2.HCl
O
S
O
S
263.1-265.5
(264)
10
11
12
13
2.5
2.0
2.0
2.5
99
5
H2N
H2N
O
O
O
S
O
S
N
N
O
H
N
H
N
O
NHAc
NH2.HCl
97.6
98.5
98.0
186.4-187.8
215.7-218.9
205.4-206.3
O
O
Me
Me
O
O
Me HN
S
NHAc
HN
S
NH2.HCl
Me
O
O
O
S
O
S
HN
NHAc
HN
NH2.HCl
O
O
O2
N
O2N
225.1-227.3
(225-227)
14
0.2
98.7
[35]
[36]
NHAc
NH2.HCl
145.1-147.5
(145-146)
15
16
17
18
19
0.1
2.5
2.6
2.7
2.4
99.8
97.6
98.0
96.7
95.4
O2
N
NHAc
O2
N
NH2.HCl
NH2.HCl
O
Et NH
O
O
220.4-222.5
230.1-232.3
190.6-192.7
215.3-217.4
NHAc
NHAc
Et NH
O
.
NH2 HCl
HO NH
HO NH
O
S
O
S
HCl.H2
N
NH
CO2Me
AcHN
NH
CO2Me
O
O
O
O
N
N
N
NH2.HCl
HN
S
NHAc
HN
S
N
O
O
a
b
c
The substrates (3 mmol) were treated with SOCl2 (2.4 mmol) in CH3OH at reflux temperature
All products were identified by IR and 1H NMR spectra
Yields refer to pure isolated products
123

A facile and efficient method
83
Table 7 Preparation of 2-chloro-N-arylacetamides
Entry
1
Compound 1a
Product 3b
Time(h)
18
Yieldc(%)
96.2
M.p. (°C)
134.2-136.5
(125-127)
Ref.
[37]
MeO
NH2
MeO
NHCOCH2Cl
116.5-119.8
(130)
2
3
12
13
74.1
91.4
[38]
[39]
Me
Br
NH2
Me
Br
NHCOCH2Cl
130.6-132.4
(113-114)
NH2
NHCOCH2Cl
NHCOCH2Cl
NHCOCH2Cl
NHCOCH2Cl
119.6-122.6
(144-146)
153.2-155.4
(150-155)
153.6-156.8
(158-160)
4
5
6
20
19
20
88.9
76.6
92.2
[40]
[41]
[42]
MeO2
Cl
C
H2N
CO2Me
NH2
Cl
F3C
NH2
F3C
Cl
Cl
99.6-101.1
(105-106)
7
8
20
13
86.7
47.7
[43]
Cl
NH2
Cl
NHCOCH2Cl
Cl
Cl
88.4-90.1
F
NH2
NH2
NH2
F
NHCOCH2Cl
NHCOCH2Cl
NHCOCH2Cl
O
S
O
S
236.1-239.3
(217)
9
12
15
20
78.2
84.5
50.4
[44]
[45]
[39]
H2N
H2N
O
O
193.7-196.5
(189-191)
10
11
O2
N
O2N
NO2
NH2
NO2
84.4-86.0
(87-89)
NHCOCH2Cl
NHCOCH2Cl
N
N
N
N
116.8-118.1
(182)
12
13
18
20
66.5
52.8
[46]
[47]
NH2
79.4-81.1
(92-94)
NH
N
NCOCH2Cl
N
N
N
COCH2Cl
N
H
N
121.1-124.2
(115-117)
14
15
20
16
56.5
81.4
[48]
S
S
COCH2Cl
H
N
N
N
N
184.9-187.1
N
N
N
N
a
The substrate(10 mmol) was treated with chloroacetyl chloride (12 mmol) in the presence of 12 mmol
K2CO3 in acetone at 15 °C
b
All products were identified by IR and 1H NMR spectra
c
Yields refer to pure isolated products
1–12), those with a aromatic heterocyclic ring (Table 8, entries 12–15) were, to
some extent, less reactive and needed more than 3 h for completion of the reaction,
but still afforded the corresponding products in excellent yields. We also found that
both N-p-tolyl benzamide and N-benzyloxycarbonyl-benzamide could not be
deacylated (not reported in this paper). Further applications of this new method
to other substrates are still in progress.
The possible mechanism for this transformation is shown in Scheme 3. It is
reasonable to assume that nucleophilic attack of alcohol on SOCl2 produces HCl.
Therefore, the mechanism proceeds through alcoholysis of N-arylacetamides (1)
123

84
G.-B. Wang et al.
Table 8 SOCl2-catalyzed deacylation of 2-chloro-N-arylacetamides
Entry
1
Compound 3a
Product 4b
Time(h) Yieldc(%)
Ref.
M.p. (°C)
185.0-186.5
(185-186)
232.1-234.2
(232-235)
2.0
2.0
99.4
99.5
[28]
MeO
NH2.HCl
MeO
NHCOCH2Cl
2
3
[29]
Me
Br
NHCOCH2Cl
Me
Br
NH2.HCl
2.0
99.6
230.1-231.9
NHCOCH2Cl
NHCOCH2Cl
NHCOCH2Cl
NHCOCH2Cl
NH2.HCl
271.6-273.0
[33]
HCl.H2N
Cl
CO2Me
4
5
6
2.0
1.2
1.0
99.9
97.9
91.4
MeO2
Cl
C
(272)
253.1-254.8
(253)
NH2.HCl
[31]
.
199.7-201.5
F3C
F3C
Cl
NH2 HCl
Cl
164.1-166.0
[32]
7
8
1.0
1.0
99.5
99.2
NH2.HCl
(164)
Cl
NHCOCH2Cl
Cl
Cl
Cl
193.2-195.0
NH2.HCl
NH2.HCl
NH2.HCl
F
NHCOCH2Cl
NHCOCH2Cl
NHCOCH2Cl
F
O
O
S
264.5-267.2
[34]
9
0.5
99.5
99.8
H2N
H2N
S
(264)
O
O
145.7-147.8
[36]
10
0.05
O2N
O2N
(145-146)
NO2
NO2
11
12
13
0.05
4.0
99.6
99.6
99.5
159.7-162.1
204.2-206.0
142.1-144.0
.
NHCOCH2Cl
NHCOCH2Cl
NH2 HCl
N
N
N
N
NH2.HCl
NCOCH2Cl
N
NH.HCl
N
5.0
N
N
H.HCl
N
COCH2Cl
N
14
15
3.5
3.0
99.4
99.6
173.5-175.0
223.2-225.1
S
S
H.HCl
COCH2Cl
N
N
N
N
N
N
N
N
a
b
c
The substrates (3 mmol) were treated with SOCl2 in CH3OH (2.4 mmol) at reflux temperature
All products were identified by IR and 1H NMR spectra
Yields refer to pure isolated products
leading to the formation of aromatic amides, which then furnish the corresponding
aromatic amine hydrochlorides (3). We tried direct use of conc. HCl as the catalyst
but yields were moderate only and longer reaction times were needed compared
with use of SOCl2 as catalyst.
Conclusion
SOCl2 in alcohol is an extremely efficient reagent system for selective deacylation
of aromatic amides. Facile conversion of aromatic amides to aromatic amine
hydrochlorides has been achieved, with the remarkable advantages of excellent
123

A facile and efficient method
85
O
S
ROH
O
+
SOCl2
RO
OH
CH3
Cl +
HCl
H
R
O
C
ROH
HCl
-Cl
Ar
N
H
CH3
Ar
N
H
Ar
N
H
CH3
1
OH
OR
H
OH
C
transfer
transfer
H
H
ArNH2
HCl
Ar
N
H
C
CH3
+
RO
CH3
OH
O
H
+
ArNH2.HCl
RO
C CH3
3
Scheme 3 Proposed mechanism for alcoholysis of N-aryl-acetamides catalyzed by SOCl2
yields, short reaction times, convenient workup, and satisfactory selectivity. The
reaction is especially suitable when aromatic amido groups are present with ester
groups, aminosulfonyl groups, or benzyloxyamide groups. We believe this reaction
could be an important addition to existing methods.
Experimental
General method
Melting points were determined by use of an X-6 sophisticated micro-melting point
apparatus and are uncorrected. The 1H NMR spectra were recorded in DMSO-d6 or
CDCl3 on a Bruker AV-300 spectrometer; chemical shifts (d) are expressed in ppm
downfield from TMS, which was used as internal standard. Coupling constant
(J) values are in Hz. The progress of the reactions was monitored by thin-layer
chromatography (TLC) using several mobile phases of different polarity. All
solvents and reagents were of chemical grade or analytical grade.
General procedure for synthesis of N-arylacetamides
To a solution of arylamine (6.0 mmol) and K2CO3 (36 mmol) in acetone (20 mL),
acetyl chloride (36 mmol) was added dropwise and the reaction mixture was stirred
at 0 °C for 0.25 h then left to warm to ambient temperature (approx. 30 °C). The
progress of the reaction was monitored by TLC. On completion, the reaction
mixture was filtered and the filtrate was evaporated with vacuum distillation to
afford the crude product, which was dispersed in a mixture of petroleum ether (PE)
and Et2O to afford analytically pure product.
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General procedure for synthesis of 2-chloro-N-arylacetamides
To a solution of arylamine (10 mmol) and K2CO3 (12 mmol) in acetone (20 mL),
2-chloroacetyl chloride (12 mmol) was added dropwise and the reaction mixture
was stirred at 0 °C for 0.5 h then left to warm to 15 °C. The progress of the
reaction was monitored by TLC. On completion, the reaction mixture was filtered
and the filtrate was evaporated with vacuum distillation to afford the crude
product, which was dispersed in a mixture of PE and Et2O to afford analytically
pure product.
General procedure for deacylation of N-arylacetamides
A mixture of N-arylacetamide (3 mmol) and thionyl chloride (2.4 mmol) was stirred
magnetically in 6 mL methanol at reflux temperature and the progress of the
reaction was monitored by TLC. The reaction mixture was evaporated with vacuum
distillation to afford the crude product. Pure product was obtained by dispersion of
the crude product in Et2O.
General procedure for deacylation of 2-chloro-N-arylacetamides
A mixture of 2-chloro-N-arylacetamide (2 mmol) and thionyl chloride (1.6 mmol)
was stirred magnetically in 6 mL methanol at reflux temperature and the progress of
the reaction was monitored by TLC. The reaction mixture was evaporated with
vacuum distillation to afford the crude product. The crude product was dispersed in
Et2O for 3 h to obtain the pure product.
Spectral data of some products
1
2-Chloro-N-(2-nitrophenyl)acetamide. H NMR (300 MHz, DMSO-d6): 10.69 (s,
1H, CONH), 8.02 (d, 1H, J = 8.1 Hz, Ar–H), 7.72–7.81 (m, 2H, Ar–H) 7.42 (t, 1H,
J = 7.7 Hz, Ar–H), 4.38 (s, 2H, CH2).
1
2-Chloro-N-(3-nitrophenyl)acetamide. H NMR (300 MHz, CDCl3): 8.44–8.46
(m, 2H, CONH and Ar–H), 8.04 (d, 1H, J = 8.7 Hz, Ar–H), 7.97 (d, 1H,
J = 8.1 Hz, Ar–H), 7.55 (t, 1H, J = 8.0 Hz, Ar–H), 4.25 (s, 2H, CH2).
1
2-Chloro-N-(4-(trifluoromethyl)phenyl)acetamide. H NMR (300 MHz, CDCl3):
8.39 (s, 1H, CONH), 7.70 (d, 2H, J = 9.0 Hz, Ar–H), 7.62 (d, 2H, J = 9.0 Hz, Ar–
H), 4.22 (s, 2H, CH2).
1
2-Chloro-N-(3,4-dichlorophenyl)acetamide. H NMR (300 MHz, CDCl3): 8.25
(s, 1H, CONH), 7.80 (s, 1H, Ar–H), 7.37–7.44 (m, 2H, Ar–H), 4.19 (s, 2H, CH2).
1
2-Chloro-N-(3-chloro-4-fluorophenyl)acetamide. H NMR (300 MHz, CDCl3):
8.25 (s, 1H, CONH), 7.72–7.75 (m, 1H, Ar–H), 7.35–7.41 (m, 1H, Ar–H), 7.13 (t,
1H, J = 9.0 Hz, Ar–H), 4.19 (s, 2H, CH2).
1
2-Chloro-N-(4-chlorophenyl)acetamide. H NMR (300 MHz, CDCl3): 8.24 (s,
1H, CONH), 7.51 (d, 2H, J = 8.7 Hz, Ar–H), 7.33 (d, 2H, J = 9.0 Hz, Ar–H), 4.19
(s, 2H, CH2).
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A facile and efficient method
87
1
N-(3-Bromophenyl)-2-chloroacetamide. H NMR (300 MHz, CDCl3): 8.22 (s,
1H, CONH), 8.01 (s, 1H, Ar–H), 7.47 (d, 1H, J = 8.7 Hz, Ar–H), 7.31 (d, 1H,
J = 8.7 Hz, Ar–H), 7.22 (t, 1H, J = 8.1 Hz, Ar–H), 4.19 (s, 2H, CH2).
Ethyl 4-(2-chloroacetamido)benzoate. 1H NMR (300 MHz, DMSO-d6): 10.67 (s,
1H, CONH), 7.93 (d, 2H, J = 9.0 Hz, Ar–H), 7.73 (d, 2H, J = 8.2 Hz, Ar–H),
4.25–4.32 (m, 4H, CH2O and CH2Cl), 1.30 (t, 3H, J = 7.1 Hz, CH3).
2-Chloro-N-(4-methoxyphenyl)acetamide. 1H NMR (300 MHz, DMSO-d6): 8.15
(s, 1H, CONH), 7.50 (d, 2H, J = 6.3 Hz, Ar–H), 6.90 (d, 2H, J = 6.3 Hz, Ar–H),
4.19 (s, 2H, CH2), 3.81 (s, 3H, CH3).
2-Chloro-N-(4-sulfamoylphenyl)acetamide. 1H NMR (300 MHz, DMSO-d6):
10.71 (s, 1H, CONH), 7.74–7.84 (m, 4H, Ar–H), 7.28 (s, 2H, SO2NH2), 4.32 (s,
2H, CH2).
1
2-Chloro-N-(4-(N-(5-methylisoxazol-3-yl)sulfamoyl)phenyl)acetamide. H NMR
(300 MHz, CDCl3): 8.42 (s, 1H, SO2NH), 8.24 (s, 1H, CONH), 7.70–7.85 (m, 2H,
Ar–H), 7.61 (d, 2H, J = 8.7 Hz, Ar–H), 6.23 (s, 1H, CH), 4.21 (s, 2H, CH2), 2.36
(s, 3H, CH3).
2-Chloro-N-(4-nitrophenyl)acetamide. 1H NMR (300 MHz, CDCl3): 8.50 (s, 1H,
CONH), 8.26 (d, 2H, J = 9.0 Hz, Ar–H), 7.77 (d, 2H, J = 9.0 Hz, Ar–H), 4.24 (s,
2H, CH2).
The following spectral data were obtained from aromatic amines (converted from
the corresponding aromatic amine hydrochlorides).
4-Amino-N-methylbenzenesulfonamide. IR (KBr): 3462, 3373, 1629, 1597, 1540,
1400,1295, 1150, 1092, 828, 680, 554 cm-1. 1H NMR (300 MHz, DMSO-d6, ppm):
7.40 (d, 2H, J = 8.4 Hz, Ar–H), 6.89–6.94 (m, 1H, SO2NH), 6.62 (d, 2H,
J = 8.7 Hz, Ar–H), 5.91 (s, 2H, NH2), 2.33 (d, 2H, J = 4.5 Hz, CH3)
4-Amino-N-cyclopropylbenzenesulfonamide. 1H NMR (300 MHz, DMSO-d6,
ppm): 7.40–7.44 (m, 3H, SO2NH and Ar–H), 6.61 (d, 2H, J = 9.0 Hz, Ar–H), 5.94
(s, 2H, NH2), 1.99–2.05 (m, 1H, CH), 0.41 (t, 2H, J = 5.3 Hz, CH2), 0.34 (t, 2H,
J = 3.6 Hz, CH2)
1
4-Amino-N-ethylbenzamide. H NMR (300 MHz, CDCl3, ppm): 7.60 (d, 2H,
J = 8.4 Hz, Ar–H), 6.65 (d, 2H, J = 8.1 Hz, Ar–H), 6.03 (s, 1H, CONH), 3.96 (s,
2H, NH2), 3.42 * 3.51 (m, 2H, CH2), 1.23 (t, 3H, J = 7.4 Hz, CH3)
4-Amino-N-hydroxybenzamide. H NMR (300 MHz, DMSO-d6, ppm): 7.62 (d,
1
1H, J = 7.5 Hz, CONH), 7.24 (d, 2H, J = 8.1 Hz, Ar–H), 6.46 (d, 2H, J = 8.7 Hz,
Ar–H), 5.54 (s, 2H, NH2), 4.13 (d, 1H, J = 6.6 Hz, OH)
Methyl 4-(4-aminophenylsulfonamido)benzoate. 1H NMR (300 MHz, DMSO-d6,
ppm): 10.46 (s, 1H, SO2NH), 7.80 (d, 2H, J = 9.0 Hz, Ar–H), 7.45 (d, 2H,
J = 8.7 Hz, Ar–H), 7.17 (d, 2H, J = 9.0 Hz, Ar–H), 6.54 (d, 2H, J = 9.0 Hz, Ar–
H), 6.05 (s, 2H, NH2), 3.78 (s, 3H, CH3)
4-Amino-N-(pyrimidin-2-yl)benzenesulfonamide. 1H NMR (300 MHz, DMSO-
d6, ppm): 11.23 (s, 1H, SO2NH), 8.47 (d, 2H, J = 4.8 Hz, Ar–H), 7.60 (d, 2H,
J = 8.7 Hz, Ar–H), 7.01 (t, 1H, J = 5.0 Hz, Ar–H), 6.54 (d, 2H, J = 8.7 Hz, Ar–
H), 5.99 (s, 2H, NH2)
123

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G.-B. Wang et al.
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