Novel one-pot synthesis of aziridines containing sydnone moiety

Article abstract of DOI:10.1080/00397910701397227

A novel series of 1,1a-dihydro-1-aryl-2-(3-aryl-sydnone-4-yl)-azirino[1,2- a] quinoxalines were prepared in a one-pot reaction of 2,3-dibromo-1-(3- arylsydnone-4-yl-)-3-arylpropan-1-one with o-phenylenediamine employing triethylamine in ethanol. The new c

Full text of DOI:10.1080/00397910701397227

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Novel One‐Pot Synthesis of Aziridines
Containing Sydnone Moiety
N. Satheesha Rai a , Balakrishna Kalluraya a & B. Lingappa a
a Department of Studies in Chemistry , Mangalore University ,
Mangalagangothri, Karnataka, India
Published online: 03 Jul 2007.
To cite this article: N. Satheesha Rai , Balakrishna Kalluraya & B. Lingappa (2007) Novel One‐Pot Synthesis
of Aziridines Containing Sydnone Moiety, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:13, 2267-2273, DOI: 10.1080/00397910701397227
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Synthetic Communicationsw, 37: 2267–2273, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701397227
Novel One-Pot Synthesis of Aziridines
Containing Sydnone Moiety
N. Satheesha Rai, Balakrishna Kalluraya, and B. Lingappa
Department of Studies in Chemistry, Mangalore University,
Mangalagangothri, Karnataka, India
Abstract: A novel series of 1,1a-dihydro-1-aryl-2-(3-aryl-sydnone-4-yl)-azirino[1,2-a]
quinoxalines were prepared in a one-pot reaction of 2,3-dibromo-1-(3-arylsydnone-
4-yl-)-3-arylpropan-1-one with o-phenylenediamine employing triethylamine in
ethanol. The new compounds were well characterized by IR,1H NMR, mass spectra,
and C,H,N analysis.
Keywords: aziridines, dibromochalcones, quinoxalines, sydnone derivatives
INTRODUCTION
The aziridine moiety represents one of the most valuable three-membered ring
systems in organic chemistry because of its versatile building-block nature for
the synthesis of many nitrogen-containing biologically active molecules.[1–4]
The aziridine moiety is present in a wide variety of natural biologically active
compounds, such as antitumor and antibiotic agents.[5] Synthetic aziridines
exhibit multiple biological properties such as enzyme inhibitors and DNA
alkylation agents.[6]
Sydnones are a novel class of mesoionic aromatic heterocycles that serve
as versatile synthetic intermediates with a masked azomethine imine unit.[7,8]
Because of their mesoionic character, they have been the subject of continual
study since their discovery. Interest in sydnone derivatives has been
Received December 1, 2006
Address correspondence to Balakrishna Kalluraya, Department of Studies in
Chemistry, Mangalore University, Mangalagangothri 574 199, Karnataka, India.
E-mail: bkalluraya_2001@yahoo.com
2267

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N. S. Rai, B. Kalluraya, and B. Lingappa
encouraged by the discovery that they exhibit various pharmacological
activities.[9,10]
Prompted by the these observations and in continuation of our research in
sydnone chemistry,[11–13] a project was undertaken to synthesize a novel
series of aziridines containing the sydnone moiety.
RESULTS AND DISCUSSION
The reaction between 2,3-dibromo-1-(3-arylsydnone-4-yl-)-3-arylpropan-1-
one 1a–f and o-phenylenediamine 2 in the presence of triethyl amine in
ethyl alcohol resulted in the formation of 1,1a-dihydro-1-aryl-2-(3-aryl-
sydnone-4-yl)-azirino[1,2-a] quinoxalines 3a–i Scheme 1. The generality of
this method with respect to various precursors is summarized in Table 1.
Scheme 1.

Table 1. Characterization data of 1,1a-dihydro-1-aryl-2-(3-aryl-sydnone-4-yl)-azirino[1,2-a] quinoxalines 3a–i
Analysis (%) found (calculated)
Yield
(%)
Nature of the
solid
Compounds
R1
R2
Mol. formula
Mol. wt.
Mp (8C)
C
H
N
3a
3b
3c
3d
3e
p-Br
p-Br
p-Br
H
Me C24H17N4O2Br 472/474
OMe C24H17N4O3Br 488/490
74
68
65
69
70
159–161 Orange crystals
144–146 Orange
60.86 (60.88) 3.52 (3.59) 11.81 (11.83)
58.84 (58.89) 3.42 (3.47) 11.51 (11.45)
60.10 (60.13) 3.25 (3.26) 12.19 (12.20)
73.10 (73.09) 4.54 (4.56) 14.20 (14.21)
H
C23H15N4O2Br 458/460
153–155 Reddish orange
138–140 Light orange
Me C24H18N4O2
394
C23H14N4O2Cl2 448/450/
452
2,6-dichloro H
162–164 Brownish orange 61.45 (61.48) 3.10 (3.11) 12.45 (12.47)
crystals
3f
3,4-methyl- OMe C25H18N4O5
ene dioxy
454
58
237–239 Light orange
66.10 (66.07) 3.94 (3.96) 12.32 (12.33)
3g
3h
3i
p-OMe
p-OMe
p-Cl
H
OMe C25H20N4O4
C24H18N4O3
410
440
55
58
69
203–205 Brownish, shining 70.21 (70.24) 4.38 (4.39) 13.64 (13.65)
184–186 Light yellowish
147–149 Orange crystals
68.17 (68.18) 4.53 (4.54) 12.71 (12.72)
67.19 (67.21) 3.95 (3.96) 13.06 (13.07)
Me C24H17N4O2Cl 428/430
Note: Solvent for recrystallization was EtOH.

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N. S. Rai, B. Kalluraya, and B. Lingappa
The starting material 2,3-dibromo-1-(3-arylsydnone-4-yl-)-3-arylpropan-1-
one 1a–f was prepared by the direct bromination of 1-(3-arylsydnone-4-yl)-
3-aryl-2-propene-1-one. These propenones were in turn obtained by the
condensation of an appropriate aldehyde with 3-substituted-4-acetyl
sydnones.[14] 3-Substituted-4-acetylsydnone was prepared according to the
procedures reported in literature.[15] A probable mechanistic pathway for
the formation of aziridine quinoxaline 3 is shown in Scheme 2.
In conclusion, we studied the reaction of sydnone dibromides with
o-phenylene diamine to get aziridines 3a–i in a one-pot reaction, and the
yields ranged from 55 to 74%.
Scheme 2. Probable mechanistic pathway.

Aziridines Containing Sydnone Moiety
EXPERIMENTAL
General
2271
Melting points were determined by the open capillary method and are uncor-
rected. All compounds were analyzed satisfactorily for C, H, and N. IR spectra
(KBr disc) were recorded on a Jasco FT IR 430 spectrophotometer. 1H NMR
spectra were recorded on Bruker AC 300F (300 MHz or 400 MHz) NMR
spectrometer using DMSO-d6 as solvent and TMS as internal standard. The
chemical shifts are expressed in d scale downfield from TMS, and proton
signals are indicated as s, singlet; d, doublet; and m, multiplet. Mass spectra
were recorded either on a Jeol JMS-D 300 mass spectrometer or API 3000
LCMS instrument operating at 70eV.
General Procedure
Preparation of 2,3-Dibromo-1-(3-arylsydnone-4-yl-)-3-arylpropan-
1-one 1a–f
1-(3-Arylsydnone-4-yl)-3-aryl-2-propene-1-one (0.1 mol) was dissolved in
glacial acetic acid (25–30 ml) by gentle warming. A solution of bromine in
glacial acetic acid (30% w/v) was added to it with constant stirring till
the yellow color of bromine persisted. The reaction mixture was stirred at
room temperature for 1–2 h. The separated solid was filtered, washed with
petroleum ether, and dried. Further purification was done by recrystallization
from ethanol.
Preparation of 1,1a-Dihydro-1-aryl-2-(3-aryl-sydnone-4-yl)-
azirino[1,2-a] Quinoxalines 3a–i
A
mixture of 2,3-dibromo-1-(3-arylsydnone-4-yl-)3-arylpropan-1-one
(0.01 mol), o-phenylene diamine (0.01 mol), and triethylamine (0.05 mol)
was dissolved in 15 ml ethanol by heating. The clear solution was allowed
to stand at room temperature for 24 h. The solid obtained was collected by fil-
tration. It was recrystallized from ethanol to afford 3a–i in 55–74% yield.
The characterization data of the compounds 3a–i are given in Table 1.
Spectral Data for Compounds 3a–i
1
3a: IR (KBr, cm21)g 1772 cm21 (Sydnone C55O), 1617 cm21(C55N). H
NMR (CDCL3, 400 MHz) d 2.49 (s, 3H, CH3); d 2.91 (d, 1H, Aziridne
C2-H); 3.67 (d, 1H, Aziridne C3-H); 6.73 (d,d,1H, Quinoxaline C4-H); 7.23
(d,d,1H, Quinoxaline C7-H); d 7.02–7.11 (m, 2H, Quinoxaline C5-H and

2272
N. S. Rai, B. Kalluraya, and B. Lingappa
C6-H); 7.24 (d, 2H, ortho protons of p-tolyl); 7.34 (d, meta protons of p-tolyl);
7.45 (d, meta protons of p-bromophenyl); 7.49 (d, ortho protons of p-bromom-
phenyl). MS, m/z, 472/474 for C24H17N4O2Br.
3b: 1H NMR (CDCl3, 300 MHz) d 3.11 (d, 1H, Aziridine C2-H); 3.41 (d, 1H,
Aziridne C3-H); 3.79 (s, 3H, OCH3); 6.81 (d, d, 1H, Quinoxaline C4-H); 7.01
(d, 2H, ortho protons of p-anisyl); 7.52 (d, 2H, meta protons of p-bromophe-
nyl); 7.68 (d, 2H, ortho protons of p- bromophenyl); 7.03–7.16 (m, 5H, Qui-
noxaline C5-H,C6-H,C7-H and meta protons of p-anisyl. MS, m/z, 488/490
for C24H17N4O3Br.
1
3c: IR (KBr, cm21) g 1749 cm21 (Sydnone C55O), 1599 cm21(C55N); H
NMR (CDCl3, 300 MHz) d 3.17 (d, 1H, Aziridine C2-H); 3.57 (d, 1H,
Aziridne C3-H); 6.54 (d, d, 1H, Quinoxaline C4-H); 7.16 (d, d, 1H, Quinoxa-
line C7-H); 7.01–7.12 (m, 2H, Quinoxaline C5-H and C6-H); 7.22 (d, 2H, meta
protons of p-bromophenyl); 7.55–7.64 (m, 5H, ArH); 7.76 (d, 2H, ortho
protons of p-bromophenyl). MS, m/z, 458/460 for C23H15N4O2Br.
1
3d: IR (KBr, cm21) g 1747 cm21 (Sydnone C55O), 1611 cm21(C55N); H
NMR (CDCL3, 300 MHz) d 2.33 (s, 3H, CH3); 3.07 (d, 1H, Aziridine
C2-H); 3.48 (d, 1H, Aziridne C3-H), 6.70 (d, d, 1H, Quinoxaline C4-H);
7.06–7.21 (m, 3H, quinaoxaline C5-H, C6-H and C7-H); 7.20 (d, 2H, ortho
protons of p-tolyl); 7.30–7.36 (m, 5H, Ar-H), 7.62 (d, 2H, meta protons of
p-tolyl). MS, m/z, 395 (Mþ þ 1) for C24H18N4O2.
3e: 1H NMR (CDCL3, 400 MHz) d 3.03 (d, 1H, Aziridne C2-H); 3.51 (d, 1H,
Aziridne C3-H); 6.78 (d, d, 1H, Quinoxaline C4-H); 7.19 (d, d, 1H, Quinoxa-
line C7-H); 7.96–7.16 (m, 2H, Quinoxaline C5-H and C6-H); 7.24–7.48
(m, 8H, Ar-H). MS, m/z, 448/450/452 for C23H14N4O2Cl2.
3f: 1H NMR (CDCl3, 400 MHz) d 2.86 (d, 1H, Aziridine C2-H); 3.61
(d, 1H, Aziridne C3-H), 3.74 (s, 3H, p-OCH3), 5.41 (s, 2H, O-CH2-O); 6.73
(d, d, 1H, Quinoxaline C4-H); 7.21 (d, d, 1H, Quinoxaline C7-H); 6.89–
7.14 (m, 2H, Quinoxaline C5-H and C6-H); 7.16 (d, 1H, C5-H of 3,4-methyle-
nedioxyphenyl); 7.27 (d, 1H, C2-H of 3,4-methylenedioxyphenyl); 7.31
(d, 1H, C6-H of methylenedioxyphenyl); 7.24 (d, 2H, ortho protons of
p-anisyl), 7.48 (d, 2H, meta protons of p-anisyl). MS, m/z, 455 (Mþ þ 1)
for C25H18N4O5.
3g: 1H NMR (CDCL3, 400 MHz) d 2.87 (d, 1H, Aziridne C2-H); 3.57 (d, 1H,
Aziridne C3-H); 3.91 (s, 3H, p-OCH3), 6.68 (d, d, 1H, Quinoxaline C4-H);
7.16 (d, d, 1H, Quinoxaline C7-H); 6.79–7.08 (m, 2H, Quinoxaline C5-H
and C6-H); 7.32 (d, 2H, ortho protons of p-anisyl); 7.51 (d, 2H, meta
protons of p-anisyl); 7.04–7.29 (m, 5H, Ar-H). MS, m/z, 411 (Mþ þ 1) for
C24H18N4O3.

Aziridines Containing Sydnone Moiety
2273
3h: MS, m/z; 441 (Mþ þ 1) for C25H20N4O4.
3i: 1H NMR (CDCL3, 400 MHz) d 2.48 (s, 3H, p-CH3); 2.92 (d, 1H, Aziridne
C2-H); 3.68 (d, 1H, Aziridne C3-H); 6.72 (d, d, 1H, Quinoxaline C4-H); 7.22
(d, d, 1H, Quinoxaline C7-H); 6.98–7.14 (m, 2H, Quinoxaline C5-H and
C6-H); 7.27–7.46 (m, 8H, ArH of p-chlorophenyl and p-tolyl). MS, m/z,
428/430 for C24H17N4O2Cl.
ACKNOWLEDGMENTS
The authors thank the head of Regional Sophisticated Instrumentation Centre
(RSIC), Chandigarh, and Central Drug Research Institute (CDRI) Lucknow
for spectral and analytical data. The authors are also thankful to University
Grants Commission (UGC), New Delhi, for the financial assistance in the
form of a major research project.
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