N-Bromosuccinimide (NBS) as Promoter for Acylation of Sydnones in the Presence of Acetic Anhydride under Neutral Conditions

Article abstract of DOI:10.3987/COM-07-11185

Various 4 - acetyl sydnones (2) can be prepared by reaction of the corresponding 3-aryl sydnones (1) with acetic anhydride at ~110 °C promoted by N-Bromosuccinimide (NBS) as an effective reagent for acylation of sydnones under neutral conditions in satisf

Full text of DOI:10.3987/COM-07-11185

HETEROCYCLES, Vol. 75, No. 2, 2008
391
HETEROCYCLES, Vol. 75, No. 2, 2008, pp. 391 - 395. © The Japan Institute of Heterocyclic Chemistry
Received, 26th July, 2007, Accepted, 17th October, 2007, Published online, 23rd October, 2007. COM-07-11185
N-BROMOSUCCINIMIDE (NBS) AS PROMOTER FOR ACYLATION
OF SYDNONES IN THE PRESENCE OF ACETIC ANHYDRIDE
UNDER NEUTRAL CONDITIONS
Hassan Ghasemnejad-Bosra,* Mina Haghdadi, and Issa Gholampour-Azizi
Islamic Azad University-Babol Branch, School of Science, P.O. Box 755, Babol.
Iran *Corresponding author; Email: h_ghasem2000@yahoo.it
Abstract – Various 4 – acetyl sydnones (2) can be prepared by reaction of the
o
corresponding 3–aryl sydnones (1) with acetic anhydride at ~110 C promoted
by N-Bromosuccinimide (NBS) as an effective reagent for acylation of
sydnones under neutral conditions in satisfactory yields.
Sydnones (1) are archetypal members of the class of compounds known as mesoionic which were first
prepared by Earl and his co-workers in 1935.1
They undergo a variety of transformations including electrophilic aromatic substitution (at the
4–position),2 cleavage with HCl to form hydrazines,3 or heterocycles4 and 1,3 – dipolar cycloadditions to
form pyrazoles or related species.5 Perhaps the biological activity: inter alia sydnone; have been used
efficaciously as antibacterial,6 antitumor,7 antimalarial,8 anti-inflammatory,9 and antihyhypertensive
agents.10 Their activity as MAO (monoamine oxidase) inhibitors has also been reported.11
Acylation occurs, with various acylation mixtures and with a large variety of 3-aryl substituents,
exclusively at the sydnone 4-position.12-16 It had been reported17 that it was not possible to acetyl-3-aryl-
sydnone with either acetic anhydride or benzoyl chloride in the presence of a lewis acid catalyst and
Friedel-Craftes conditions to obtain the 4-acetylsydnone because the difficulties stem from the fact that
using the standard Friedel-Craftes conditions (acid chloride/aluminum chloride) the sydnones do not react,
presumably due to coordination of the lewis acid with the exocyclic oxygen atom in the sydnone.18
Successful acylation has relied on the use of alkyl anhydrides and acids such as perchloric,19 phosphoric20
or boron trifluoride or alkyl carboxylicacids and phosphorus pentoxide.21 More recently, Montmorillonite
K-1022 and HClO4 under high powered ultrasonic bath23 have been reported as efficient catalysts for
acylation of 3- substituted sydnones in the presence acetic anhydride.

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HETEROCYCLES, Vol. 75, No. 2, 2008
Ar
Ar
N +
N +
O
N
O
N
O
NBS , Ac2O, reflux
Me
O-
O-
2a-j
1a-j
Ar: (a) C6H5 , (b) 2-MeC6H4 , (s) 4-MeC6H4 ,(d) 2-MeOC6H4 , (e) 4-MeOC6H4
(f) 2-NO2C6H4 , (g) 4-NO2C6H4 , (h) 4-ClC6H4 , (i) 2,4-Cl2C6H3 , (j) 4-Br-C6H4
Scheme 1
In this work, we have observed that NBS 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 (Table 1).
Table 1: Acetylation of the 3-arylsydnones 1a-j to the corresponding 4-acetyl-
sydnones 2a-j by NBS in Ac2O under reflux
Entry
Product a
Yield (%) b
Mp(oC)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
95
90
91
90
93
90
92
93
90
94
143-145
105-107
119-120
104-105
97-98
151-152
208-210
129-131
98-99
10
2j
169-170
aAll the isolated products were characterized on the basis of their physical and
1H-NMR, 13C-NMR, IR spectral analysis and by direct comparison with literature
data.17, 19, 24, 25
bPurified Yields.
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 occur when equimolar amounts of 3-arylsydnones and NBS are used in the
reactions. Longer reaction times are required when lesser amounts of NBS are employed. It is also
important to note that, no acetylated products were afforded when the reactions were carried out in the
absence of NBS. This substantiates the vitality of N-bromosuccinimide in promoting the reactions
probably by converting acetic anhydride into a more reactive acetylating reagent. The advantages or the
characteristic aspects of the described method in this paper in comparison with other previously reported
are the following: The yields of acylated products are better than the pervious reported yields. In addition,
the catalyst NBS is inexpensive, no moisture sensitivity, no large amount of NBS required, and no special
efforts are required for the reaction.

HETEROCYCLES, Vol. 75, No. 2, 2008
393
Table 2: IR, 1H-NMR and 13C-NMR spectral data of the 4-acetyl sydnones 2a-j
Product a
IR (KBr) (cm-1)
1H-NMR (CDCl3) (ppm)
13C-NMR (CDCl3) (ppm)
2a
3060,1763,1665,1426 2.39 (s, Me, 3H), 8.01-8.39 (m, 5H)
1053,770
28.14 (COMe), 108.3 (C4), 126.21,
131.25, 136.72, 144.63 (Ar), 166.7
(C5), 183.80 (CO)
2b
3053,1780,1660,1425 2.36 (s, Me, 3H ), 2.69 (s, 3H), 7.93 – 16.30 (Me), 28.32 (COMe), 108.40
8.30 (m, 3H), 8.69-8.73 (m, 1H)
(C4), 115.19, 132.46, 134.57, 138.30,
138.60, 143.30 (Ar), 165.40 (C5),
184.30 (CO)
1250,795
2c
2d
2e
2f
3058,2933,1783,1678 2.38 (s, Me, 3H), 2.61 (s, 3H), 7.50 - 21.30 (Me), 28.32 (COMe), 107.40
7.55 (dd, 2H), 7.85 -7.90 (dd, 2H)
(C4), 124.97, 128.59, 140.27 (Ar),
165.80 (C5), 184.10 (CO)
1509,1316,1050,827
3080,1780,1680,1489 2.58 (s, Me, 3H), 3.84 (s, 3H), 7.80- 28.23 (COMe), 56.50 (OMe), 108.74
7.86 (m, 2H),8.45-8.56 (m, 2H)
(C4), 118.07, 124.78, 132.11, 132.32,
149.10 (Ar), 166.70 (C5), 184.42 (CO)
1431,1038,770
3085,1786,1675,1491 2.63 (s, Me, 3H), 3.94 (s, 3H), 7.22-
28.41 (COMe), 55.72 (OMe), 107.30
(C4), 126.57, 129.50, 139.69, 158.32
(Ar), 166.20 (C5), 184.20 (CO)
7.26(dd, 2H),7.82-7.86 (dd, 2H)
1442,1055,485
3098,1788,1672,1537 2.47 (s, Me, 3H), 7.56 (m, 1H),
27.50 (COMe), 106.90 (C4), 126.10,
128.20, 128.80, 133.40, 133.90, 143.30
(Ar), 165.10 (C5), 184.80 (CO)
7.92(m, 2H), 8.44 (m, 1H)
1359,1052,848,788
2g
2h
2i
3100,1795,1670,1530 2.58 (s, Me, 3H), 8.26-8.29 (dd, 2H)
28.20 (COMe), 106.70 (C4), 126.87,
130.80, 139.29, 148.26 (Ar), 165.80
(C5), 184.30 (CO)
8.80-8.85 (dd, 2H)
1350,1055,850,792
3100,1786,1663,1438 2.60 (s, Me,3H),7.92-7.95 (m, 2H)
27.90 (COMe), 106.60 (C4), 127.01,
137.80, 140.27, 148.86 (Ar), 165.80
(C5), 184.10 (CO)
8.52-8.56 (m, 2H)
1090,838
3110,1790,1660,1440 2.40 (s, Me, 3H),7.86-.88 (q, 1H),
27.20 (COMe), 107.50 (C4), 123.98,
127.43, 132.96, 141.56, 142.42, 145.33
(Ar), 165.60 (C5), 184.80 (CO)
8.48 -8.50 (q, 1H),8.98 (q, 1H)
1100,840
2j
3095,1770,1675,1428 2.58 (s, Me, 3H), 7.81-7.86 (dd,
27.50 (COMe), 106.80 (C4), 126.90,
128.50, 133.20, 134.80 (Ar), 165.90
(C5), 184.00 (CO)
2H) , 8.61-8.66 (dd, 2H)
1035,1039,770
aAll the isolated products were characterized on the basis of their physical and 1H-NMR, 13C-NMR, IR spectral analysis
and by direct comparison with literature data.17, 19, 24, 25
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. All melting points were determined on Büchi 530 melting point
apparatus, and 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 (1 mmol) was added NBS
o
(0.018 g, 1 mmol), and the mixture was refluxed at ~110 C for 4 h. After complete conversion of the
substrates as indicated by TLC using EtOAc/hexane mixture (1:1), the resulting reaction mixture was

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HETEROCYCLES, Vol. 75, No. 2, 2008
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 EtOH (95%) to yield pure crystals of the products
(2a-j) in 90-95% 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.17, 19, 24, 25
ACKNOWLEDGEMENTS
We wish to thank the Islamic Azad University-Babol Branch, Babol, Iran, for financial support to carry
out this research.
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