1,3-Dibromo-5,5-dimethylhydantoin (DBH) as an efficient promoter for acetylation of 3-arylsydnones in the presence of acetic anhydride under neutral conditions

Article abstract of DOI:10.1002/jhet.5570440231

(Chemical Equation Presented) 1,3-Dibromo-5,5-dimethylhydantoin (DBH) has been found to efficiently promote the conversion of various 3-arylsydnones to their 4-acetyl congeners in the presence of acetic anhydride under neutral conditions in satisfactory y

Full text of DOI:10.1002/jhet.5570440231

Mar-Apr 2007
467
1,3-Dibromo-5,5-dimethylhydantoin (DBH) as an Efficient
Promoter for Acetylation of 3-Arylsydnones in the presence of
Acetic Anhydride under Neutral Conditions
Davood Azarifar,*a Hassan Ghasemnejad Bosraa and Mahmood Tajbakshb
aChemistry Department, School of Science, Bu-Ali Sina University, Postal Code 65174, Hamadan, Iran.
bChemistry Department, Faculty of Science, Mazandaran University, Babolsar, Iran. *Corresponding Author;
E-mail: azarifar@basu.ac.ir
Received April 12, 2006
Ar
N
+
Ar
N
+
O
H
DBH, Ac2O
reflux
N
N
O
O
O
O
1,3-Dibromo-5,5-dimethylhydantoin (DBH) has been found to efficiently promote the conversion of
various 3-arylsydnones to their 4-acetyl congeners in the presence of acetic anhydride under neutral
conditions in satisfactory yields.
J. Heterocyclic Chem., 44, 467 (2007).
Sydnones such as 1 belong to a class of heterocyclic
substituted sydnones in the presence of acetic anhydride
[22].
In connection with our ongoing research on 1,3-
dibromo-5,5-dimethylhydantoin (DBH) as a versatile and
convenient reagent used in various transformations [23-
27], and also in order to avoid the drawbacks related to
compounds known as mesoionic [1-2], were first prepared
by Earl and Mackney in 1935 [3]. Sydnones are normally
prepared by dehydrative cyclization of N-nitrosamino
acids [4] regarded as dipolar structures. Sydnones have
attracted an inordinately large research effort over the
years owing to their biological value as antibacterial [5],
antitumour [6], antimalarial [7], anti-inflammatory [8],
and antihypertensive [9] agents. Among various
transformations that sydnones undergo, are electrophilic
substitution reactions that normally occur at the 4-position
(if unsubstituted) [1,10]. Also, the dipolar nature of
sydnones leads to reactions in which they serve as 1,3-
dipoles in cycloadditions to form pyrazoles or related
species [11].
Scheme I
Ar
N
+
Ar
N
+
O
DBH, Ac2O
reflux
H
N
N
O
O
O
O
1a-j
2a-j
Ar:
(a) C6H5, (b) 2-MeC6H4, (c) 4-MeC6H4, (d) 2-MeOC6H4,
(e) 4-MeOC6H4, (f) 2-O2NC6H4, (g) 4-O2NC6H4, (h)
4-ClC6H4, (i) 2,4-Cl2C6H3, (j) 4-BrC6H4
3-Arylsydnones have been subjected to substitution
with the vast majority of electrophiles. This can be
accounted for by the deactivation of the aryl substituent
due to the electron-withdrawing effect of the sydnone
ring N-3 position that bears a substantial fractional
positive charge [12,13]. Acylation of sydnones, among
other aromatic substitution reactions, is of considerable
interest in organic synthesis that has been implemented
by various reagents exclusively at the sydnone 4-
positions as already mentioned [14-16]. It has been
reported that the Lewis acid-catalyzed acylation of 3-
arylsydnones with either acetic anhydride or benzyl
chloride under Friedel-Crafts conditions fails to produce
4-acylsydnones [17], presumably due to coordination of
a Lewis acid catalyst with the negatively charged
exocyclic oxygen atom bonded to the sydnone ring [18].
However, successful acylations of sydnones by alkyl
anhydrides using different acids have been reported [19-
21]. More recently, Montmorillonite K-10 has been
reported as an efficient catalyst for acylation of 3-
the previously reported methods such as the use of acidic
media, low reaction yields and troublesome extraction and
purification of the products from reaction mixtures, we
wish, herein, to report on the reagent DBH as a more
robust and efficient promoter for the acetylation of
sydnones to their corresponding 4-acetyl derivatives. A
similar protocol for the acetylation of alcohols by using
acetic anhydride and 1,3-dibromo-5,5-dimethylhydantoin
has recently been reported by Zolfigol and his co-workers
[28]. In this work, we have observed that 1,3-dibromo-
5,5-dimethylhydantoin can efficiently enhance the
conversion of the 3-arylsydnones 1a-j to their 4-acetyl
congeners 2a-j in the presence of acetic anhydride under
reflux (Scheme I, Table 1). According to the results
shown in the table 1, the reactions proceed within few
hours at 100 °C in satisfactory yields. Numerous
repetitions of the reactions under different molar
conditions indicated that, the most effective conversions

468
D. Azarifar, H. G. Bosra and M. Tajbaksh
Vol 44
occur when equimolar amounts of 3-arylsydnones and
DBH are used in the reactions. Longer reaction times are
required when lesser amounts of DBH are employed. It is
also important to note that, no acetylated products were
afforded when the reactions were carried out in the
absence of DBH. This substantiates the vitality of DBH in
promoting the reactions probably by converting acetic
anhydride into a more reactive acetylating reagent.
EXPERIMENTAL
Chemicals were obtained from Merck and Fluka chemical
companies. IR spectra were recorded using a Shimadzu 435-U-
04 spectrophotometer (KBr pellets) and NMR spectra were
obtained in CDCl3 using a 90 MHz JEOl FT NMR spectrometer.
Mass spectra were recorded on
a
GCMS-QP1100EX
spectrometer. All melting points were determined on a Büchi
530 melting point apparatus, and are reported uncorrected.
General Procedure for Acetylation of 3-Arylsydnones 1a-j
to the corresponding 4-Acetyl Derivatives 2a-j. To a stirred
solution of 3-arylsydnone 1a-j (1 mmol) in acetic anhydride (2
mmol) was added DBH (0.29 g, 1 mmol), and the mixture was
refluxed at 100 °C for 7 h. After complete conversion of the
substrates as indicated by TLC using ethylacetate/hexane
mixture (1:1), the resulting reaction mixture was poured into ice
water to destroy the excess acetic anhydride and neutralized with
sodium carbonate. The resulting mixture was filtered, the filtrate
was extracted with CH2Cl2 (2x25 mL), and then dried with
anhydrous MgSO4. After filtration, the solvent was evaporated
under reduced pressure to leave a solid brown residue, which
was recrystallized from warm ethanol (95%) to yield pure
crystals of the products 2a-j in 80-92% yield (Table 1). The
products were characterized on the basis of their physical and
spectral analysis (Table 2) and by direct comparison with
literature data [20,22,29].
Table 1
Acetylation of the 3-aryl sydnones 1a-j to the
corresponding 4-acetyl sydnones 2a-j by DBH in Ac2O
under reflux
Entry
Product
Yield (%) a
Mp (°C)
1
2
2a
2b
2c
2d
2e
2f
92
83
87
81
85
80
82
90
80
89
143-145
105-107
119-120
104-105
97-98
3
4
5
6
151-152
208-210
129-131
98-99
7
2g
2h
2i
8
9
Acknowledgement. We wish to thank the University of Bu-
Ali Sina, Hamadan, Iran, for financial support to carry out this
research.
10
2j
169-170
a Purified Yields.
Table 2
IR, 1H-NMR, 13C-NMR and MS (ET) spectral data of the 4-acetyl sydnones 2a-j
1H-NMR (CDCl3) (ppm) 13C-NMR (CDCl3) (ppm)
Product
IR (KBr) (cm-1)
MS (m/z)
2a
3060, 1763, 1665, 2.36 (s, 3H, COMe), 8.01-8.39 (m, 5H, Ar)
1426, 1053, 770
28.14 (COMe), 108.3 (C4), 126.21, 204, 161, 149, 147, 145,
131.25, 136.72, 144.63 (Ar), 166.7 (C5), 105, 104, 77, 76, 63, 51,
183.80 (CO)
3053, 1780, 1660, 2.39 (s, 3H, COMe), 2.69 (s, 3H, Me), 7.93 - 16.30 (Me), 28.32 (COMe), 108.40 (C4), 218, 175, 161, 160, 138,
1425, 1250, 795 8.30 (m, 3H, Ar), 8.73 - 9.00 (m, 1H, Ar) 115.19, 132.46, 134.57, 138.30, 138.60, 118, 90, 89, 77, 64, 50,
143.30 (Ar), 165.40 (C5), 184.30 (CO) 43
3058, 2933, 1783, 2.38 (s, 3H, COMe), 2.61 (s, 3H, Me), 7.47 - 21.30 (Me), 28.32 (COMe), 107.40 (C4), 218, 175, 160, 159, 138,
50, 43
2b
2c
2d
2e
2f
1678, 1509, 1316, 7.93 (m, 4H, Ar)
1050, 827
124.97, 128.59, 140.27 (Ar), 165.80 118, 90, 89, 77, 64, 63,
(C5), 184.10 (CO) 51, 50, 43
3080, 1780, 1680, 2.58 (s, 3H, COMe), 3.84 (s, 3H, OMe), 7.80 - 28.23 (COMe), 56.50 (OMe), 108.74 234, 218, 191, 178, 176,
1489, 1431, 1038, 8.45 (dd, 4H, Ar)
770
(C4), 118.07, 124.78, 132.11, 132.32, 134, 107, 92, 90, 64, 53,
149.10 (Ar), 166.70 (C5), 184.42 (CO) 43
3085, 1786, 1675, 2.63 (s, 3H, COMe), 3.94 (s, 3H, OMe ), 7.22 28.41 (COMe), 55.72 (OMe), 107.30 234, 219, 191, 176, 134,
1491, 1442, 1055, -7.822 (m, 4H, Ar)
485
(C4), 126.57, 129.50, 139.69, 158.32 107, 89, 92, 64, 52, 43
(Ar), 166.20 (C5), 184.20 (CO)
3098, 1788, 1672, 2.47 (s, 3H, COMe), 7.56 - 8.44 (m, 4H, Ar)
1537, 1359, 1052,
27.50 (COMe), 106.90 (C4), 126.10, 249, 206, 191, 149, 103,
128.20, 128.80, 133.40, 133.90, 143.30 92, 77, 75, 64, 63, 52,
848, 788
3100, 1795, 1670, 2.58 (s, 3H, COMe), 8.26 - 8.80 (m, 4H, Ar)
1530, 1350, 1055,
(Ar), 165.10 (C5), 184.80 (CO)
28.20 (COMe), 106.70 (C4), 126.87, 249, 206, 191, 149, 122,
130.80, 139.29, 148.26 (Ar), 165.80 103, 92, 77, 75, 64, 63,
50, 45, 43
2g
2h
2i
850, 792
(C5), 184.30 (CO)
27.90 (COMe), 106.60 (C4), 127.01, 240, 238, 182, 180, 149,
52, 50, 45, 43
3100, 1786, 1663, 2.60 (s, 3H, COMe), 7.92 - 8.56 (m, 4H, Ar)
1438, 1090, 838
137.80, 140.27, 148.86 (Ar), 165.80 140, 138, 133, 110, 77,
(C5), 184.10 (CO)
27.20 (COMe), 107.50 (C4), 123.98, 276, 274, 272, 229, 214,
64, 52, 43
3110, 1790, 1660, 2.40 (s, 3H, COMe), 7.86 - 8.98 (m, 3H, Ar)
1440, 1100, 840
127.43, 132.96, 141.56, 142.42, 145.33 172, 145, 125, 110, 78,
(Ar), 165.60 (C5), 184.80 (CO)
27.50 (COMe), 106.80 (C4), 126.90, 284, 282, 241, 239, 226,
75, 63, 49, 43
2j
3095, 1770, 1675, 2.58 (s, 3H, COMe), 7.81- 8.61 (m, 4H, Ar)
1428, 1035, 1039,
770
128.50, 133.20, 134.80 (Ar), 165.90 224, 184, 182, 158, 156,
(C5), 184.00 (CO)
146, 77, 76, 66, 52, 43

Mar-Apr 2007
1,3-Dibromo-5,5-dimethylhydantoin (DBH) as an Efficient Promoter for Acetylation
469
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