N,N,N′,N′-Tetrabromobenzene-1,3-disolfonamide (TBBDS) as an efficient promoter for one-pot conversion of N-arylglycines to sydnones in the presence of NaNO2/Ac2O under neutral conditions

Article abstract of DOI:10.3987/COM-06-10859

N,N,N′,N′-Tetrabromobenzene-1,3-disolfonamide (TBBDS)-promoted one-pot conversion of various N-arylglycines to sydnones using a combination of NaNO₂ and Ac₂O has been achieved efficiently through N-nitrosation followed by cyclization

Full text of DOI:10.3987/COM-06-10859

HETEROCYCLES, Vol. 68, No. 11, 2006
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HETEROCYCLES, Vol. 68, No. 11, 2006, pp. 2343 - 2347. © The Japan Institute of Heterocyclic Chemistry
Received, 7th August, 2006, Accepted, 20th September, 2006, Published online, 22nd September, 2006. COM-06-10859
N,N,N',N'-TETRABROMOBENZENE-1,3-DISOLFONAMIDE (TBBDS) AS
AN EFFICIENT PROMOTER FOR ONE-POT CONVERSION OF N-
ARYLGLYCINES TO SYDNONES IN THE PRESENCE OF NaNO2/Ac2O
UNDER NEUTRAL CONDITIONS
Davood Azarifar,*a Hassan Ghasemnejad-Bosra,a Ramin Ghorbani-Vaghei,a
and Mahmood Tajbakshb
aDepartment of Chemistry, School of Science, Bu-Ali Sina University, Postal
b
Code 65174, Hamadan, Iran. Department of Chemistry, Faculty of Science,
Mazandaran University, Babolsar, Iran. *Corresponding author; Fax
+98(811)8272404; E-mail: azarifar@basu.ac.ir
Abstract– N,N,N',N'-Tetrabromobenzene-1,3-disolfonamide (TBBDS)-promoted
one-pot conversion of various N-arylglycines to sydnones using a combination of
NaNO2 and Ac2O has been achieved efficiently through N-nitrosation followed
by cyclization in high yields (85-95%) under mild and neutral conditions.
Sydnones (cf. 2) are unique members of the class of heterocyclic compounds known as mesoionic.1
Sydnones were first prepared by Earl and Mackney in 1935,2 and the greatest interest in them, ever since,
stems from their biological activity as antibacterial,3 antitumour,4 antimalarial,5 anti-inflammatory,6 and
antihypertensive7 agents. Sydnones also undergo a variety of transformations including electrophilic
aromatic substitution (at the 4-position),8 1,3-dipolar cycloaddition reactions to form pyrazoles or related
species,9 and cleavage to hydrazines2 or heterocycles10 when treated with HCl.
Sydnones are intrinsically neutral substances that are normally prepared by dehydrative cyclization of
N-nitrosamino acids.11 N-Nitrosamino acids used in the synthesis of sydnones are themselves prepared
from N-nitrosation of amino acids. N-Nitrosation is a well-known reaction in organic synthesis12 that is
usually accomplished by nitrous acid generated from the treatment of sodium nitrite with an aqueous
mineral acid.13
In continuation of our research on various transformations by halogenating agents14-16 and sydnones,17-19
and also in order to avoid the drawbacks generally caused by the use of strong acidic media in nitrosation
reactions, we wish, herein, to report on the N,N,N',N'-tetrabromobenzene-1,3-disolfonamide (TBBDS) as

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HETEROCYCLES, Vol. 68, No. 11, 2006
a more robust and efficient promoter for one-pot conversion of N-arylglycines to sydnones under neutral
conditions. In this work we have observed that N,N,N',N'-tetrabromobenzene-1,3-disolfonamide
(TBBDS) can efficiently enhance the conversion of the N-arylglycines (1a-j) to the sydnones (2a-j)
using sodium nitrite and acetic anhydride in CH2Cl2 in satisfactory yields (85-95 %) (Scheme 1, Table
1). As shown in the table, the reactions occur satisfactorily within 5-8 h at 0-5 ˚C. The experimental
results indicated that the most effective conversion occurs if the molar N-arylglycines/TBBDS ratio is
maintained at 4. Longer reaction times are required when lesser amounts of TBBDS are employed. It is
important to note that no sydnones were afforded when the reactions were carried out without using any
TBBDS in the reaction. In accordance with the previously reported action of acetic anhydride in the
cyclization of N-nitrosoglycines to sydnones,2 and also the crucial role of the acetyl hypobromite,
generated from the reaction of acetic anhydride with hypobromous acid during the reaction, in
N-bromination of sulfonamide,20 we propose a possible mechanism for these reactions as shown in
Scheme 2, in which the cyclization of the intermediate N-nitrosoglycines is, probably, activated by
TBBDS.
A
r
N
TBBDS, NaNO2 , Ac2O
in CH2Cl2, 0-5
ArNHCH CO H
2
2
+
C
N
O
O
1a-j
2a-j
Scheme 1
Table 1 Conversion of the N-arylglycines (1a-j) to the sydnones (2a-j) with a combination of
NaNO2 /Ac2O in CH2Cl2 promoted by TBBDS.
Entry
Producta
Ar
Time (h)
Yield (%)b
mp (˚C)
Reported20,21
Found
98
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
o-CH3C6H4
p-CH3C6H4
o-CH3OC6H4
p-CH3OC6H4
p-NO2C6H4
o-NO2C6H4
p-ClC6H4
7.0
6.0
6.0
5.5
6.0
8.0
7.0
7.8
6.2
5.0
92
90
93
89
88
85
91
85
93
95
97
145
97
143
96
126
147
184
114
94
125
148
184
113
96
2g
2h
2i
2,4-Cl2C6H3
p-BrC6H4
138
134
137
135
10
2j
C6H5
a
All the isolated products were characterized on the basis of their physical properties and H NMR, 13C NMR
and IR spectra and by direct comparison with literature data.2,8,21,22
1
b
Isolated yields.

HETEROCYCLES, Vol. 68, No. 11, 2006
2345
O
O
O
O
O
Na
Br
O
Na
O
S
Br
S
O
Br
N
O
S
S
+
N
Br
N
Br
Br
N
+
N
Br
N
Br
O
O
O
O
O
O
+
Br
N O
Br
N
O
O
Br
S
S
N
Br
H
N
H
O
O
O
O
Ar
O
Ar
O
O
O
Br
N
N
Br
N
N
+
N
O
S
S
N
+
N
Ar
HN
Br
OH
Br
OH
O
OH
O
O
O
Br
Br
Ac2O
O
+
AcO
+
O
S
O
O
O
O
O
O
Br
Br
Br
H
S
S
S
+
+
N
Br
N
Br
H
Br
N
Br
N
Br
O
O
O
O
O
O
Ar
O
H
O
O
O
Ar
O
Br
N
S
N
N
S
S
+
S
OBr
OH
N
Br
Br
N
N
Br
Br
N
O
N
O
O
O
OH
O
O
Br
Br
-
Br
O
Ar
N
Ar
N
O
O
Br
- H
S
+
S
N
HN
Br
N
Br
N
O
OH
O
O
O
O
Scheme 2
EXPERIMENTAL
Chemicals were obtained from Merck and Fluka Chemical Companies. IR spectra were recorded using a
Shimadzu 435-U-04 spectrophotometer (KBr pellets) and 1H NMR and 13C NMR spectra were obtained
in CDCl3 using 90 MHz JEOL FT NMR spectrometer. All melting points were determined on a Büchi
530 melting point apparatus, and reported uncorrected.
Conversion of the N-Arylglycines (1a-j) to the Sydnones (2a-j) with NaNO2/Ac2O using TBBDS;
General Procedure
To a magnetically stirred solution of N-arylglycine (1) (2 mmol) in CH2Cl2 (40 mL), was added
N,N,N',N'-tetrabromobenzene-1,3-disolfonamide (TBBDS) (0.5 mmol), NaNO2 (0.17 g, 2.5 mmol) and
Ac2O (0.31 g, 3 mmol) at 0-5 ْC. After the complete conversion of the substrate in 5-8 h (Table 1) as
monitored by TLC using AcOEt/hexane mixture (1:1), the reaction mixture was poured into water (5
mL), and then solid NaHCO3 was added cautiously with stirring to remove the remaining glycines. The
resulting mixture was filtered, the filtrate was extracted with CH2Cl2, and then the organic layer was
separated, dried and evaporated in vacuo to leave the solid product (2), which was further purified by

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HETEROCYCLES, Vol. 68, No. 11, 2006
recrystallization from EtOH. These products were characterized on the basis of their physical properties
and also their IR and NMR spectra with direct comparison with literature data.2,8,21,22
ACKNOWLEDGEMENT
We wish to thank the University of Bu-Ali Sina, Hamadan, Iran, for financial support to carry out this
research.
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