Synthesis and evaluation of antibacterial activity of new derivatives of pyrimido[4,5-e][1,3,4]oxadiazine

Article abstract of DOI:10.1515/HC.2011.009

New derivatives of pyrimido[4,5-e][1,3,4]oxadiazine were prepared and their antibacterial evaluations were performed on four different Gram-negative and Gram-positive bacteria. Copyright by Walter de Gruyter Berlin Boston.

Full text of DOI:10.1515/HC.2011.009

Heterocycl. Commun., Vol. 17(1-2), pp. 49–52, 2011 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/HC.2011.009
Synthesis and evaluation of antibacterial activity of new
derivatives of pyrimido[4,5-e][1,3,4]oxadiazine
Mehdi Bakavoli1,*, Mohammad Rahimizadeh1,
(1999) synthesized some tetrahydro[1,2-d][1,3,4]oxadiazine
derivatives and studied the conformational preference by NMR
spectroscopy and X-ray analysis. More recently, 1,3,4-oxadi-
Ali Shiri1, Hossein Eshghi1, Simin Vaziri-Mehr2,
Parvaneh Pordeli3 and Mohsen Nikpour4
azine-5,10-dione derivatives were also obtained (Shindy et al.,
1 Department of Chemistry, School of Sciences, Ferdowsi
2006). In addition, thiazolo[4,3-b][1,3,4]oxadiazine-6(4H)-
University of Mashhad, 91775-1436 Mashhad, Iran
thiones were synthesized by the reaction of 3-aminorhodanine
2 Department of Chemistry, School of Sciences, Islamic
with 1,1,2,2-ethenetetracarbonitrile (Mourad et al., 2007). In
Azad University, Mashhad Branch, Mashhad, Iran
pursuing our research on the synthesis of fused heterocyclic
3 Department of Biology, School of Sciences, Ferdowsi
compounds with potential biological activities (Bakavoli et
University of Mashhad, Mashhad, Iran
al., 2007, 2008a,b, 2009, 2010) and taking into account the
4 Department of Chemistry, School of Sciences, Islamic
literature reports on biological activities of fused oxadiazines,
Azad University, Ahvaz Branch, Ahvaz, Iran
in this paper we describe the synthesis of new pyrimido[4,5-e]
[1,3,4]oxadiazines and their antibacterial evaluations.
*Corresponding author
e-mail: mbakavoli@yahoo.com
Results and discussion
Chemistry
Abstract
New derivatives of pyrimido[4,5-e][1,3,4]oxadiazine were
prepared and their antibacterial evaluations were performed
on four different Gram-negative and Gram-positive bacteria.
5-Bromo-2-chloro-6-methyl-4-(1-methylhydrazino)pyrimi-
dine (2) was prepared by the reaction of 5-bromo-2,4-dichlo-
ro-6-methyl pyrimidine (1) with methylhydrazine according
to our previously published method (Bakavoli et al., 2006).
Treatment of 2 with aroyl halides in the presence of K2CO3
in boiling acetonirile afforded the new derivatives of the
pyrimido[4,5-e][1,3,4]oxadiazine 3a–h (Scheme 1).
Keywords: antibacterial evaluation; heterocyclization;
pyrimidooxadiazine.
The structures of new compounds were elucidated by their
spectral and micronalytical data. For example, the H NMR
Introduction
1
The synthesis of fused oxadiazines has been a challenging sub-
ject. These compounds with diverse biological activities are
reported to act as inhibitors of bacterial growth (Barbaric et al.,
2003), antimicrobial agents (Berkowitz et al., 1977; Shindy
et al., 2006), useful intermediates in the synthesis of tenidap
prodrugs or β-lactam antibiotics, especially in the synthesis
of carbapenems and penems (Gravestock, 1987; Robinson
and Donahue, 1994), cardiovascular antibacterial and plant
growth regulating agents with miticidal, nematocidal, acri-
cidal, insecticidal and anticonvulsive activities (Kornet, 1996;
Khan et al., 2002). The methods for the synthesis of oxadiaz-
ines, especially [1,3,4]oxadiazine systems, are limited (Elliot
and Gibson, 1980; Kim and Kurasawa, 1998). The treatment
of (-)-2-methyl-2-(α-methyl-β-hydroxyphenyl)benzoic acid
hydrazide with sulfuric acid (Trepanier et al., 1965) or N′-
chloroacetyl salicyl hydrazide with NaOH in DMF (Gaozza
and Lamdan, 1970) leads to the formation of [1,3,4]oxadi-
azine derivatives. Elliot and Gibson (1972) and Shawali and
Hassaneen (1977) reported the synthesis of 1,3,4-benzoxadi-
azines from hydrazidoyl bromides. The reaction of ortho-mer-
captobenzohydrazide with chloroacetyl chloride gave a [1,3,4]
oxadiazine derivative (Freeman et al., 1975). Rosling et al.
spectrum of compound 3d does not exhibit the signal at δ 4.21
belonging to the NH2 moiety of the precursor 2 but shows two
singlets at δ 2.22 and 3.21 for the methyl signals of the pyrim-
idine and oxadiazine rings, respectively. The spectrum also
shows two doublets at δ 7.33 and 7.74 (J=8 Hz) for the aro-
matic ring protons. The IR spectrum is devoid of the stretch-
ing vibration bands at 3360 and 3280 cm-1 for the NH2 moiety
that is observed in the spectrum of the precursor 2. The band
at 1660 cm-1 for the carbonyl group of 2 is also absent in the
spectrum of 3d. In the mass spectrum of 3d the molecular ion
peaks are observed at m/z 319 and 321, which is consistent
with the presence of a chlorine atom in the molecule. These
results together with the microanalytical data fully support
the molecular formula C13H10Cl2N4O. Further treatment of
compound 3a, as an example, with selected secondary amines
in boiling ethanol led to the displacement of the chlorine atom
and gave the substituted products 4a–e (Scheme 2).
Biological activities
The newly synthesized compounds 3a–h and 4a–e
were screened for the antibacterial activity against
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50 M. Bakavoli et al.
CH3
N
CH3
N
Cl
N
Cl
Br
Cl
N
Cl
N
NH2
N
ArCOCl
MeNHNH2
CHCl3
N
N
N
Br
O
K2CO3, CH3CN
CH3
1
CH3
2
CH3
R
3a-h
3a: Ar=C6H5-, 3b: Ar=2-Cl-C6H4-, 3c: Ar=3-Cl-C6H4-,
3d: Ar=4-Cl-C6H4-, 3e: Ar=4-Br-C6H4-, 3f: Ar=3-NO2-
C6H4-, 3g: Ar=4-NO2-C6H4-, 3h: Ar=4-CH3-C6H4-,
Scheme 1 Synthesis of compounds 3a–h.
CH3
CH3
Cl
N
N
R'2N
N
N
R'2NH
N
N
N
N
EtOH (reflux)
O
O
CH3
3a
CH3
4a-e
R'2NH: 4a:
4b:
4c:
4d:
4e:
O
NH
NH
Me N
NH
Et N
NH
NH
Scheme 2 Synthesis of compounds 4a–e.
several pathogenic representative Gram-positive bacteria
(Staphylococcus aureus PTCC 1074 and Bacillus subtilis
PTCC 1365) and Gram-negative bacteria (Escherichia coli
BA 7601C and Pseudomonas aeruginosa PTCC 1431) using
the disc diffusion sensitivity test (Cruickshank et al., 1975;
Collins, 1976). Mueller-Hinton agar media were sterilized for
15 min at 120°C and poured into the plates to a uniform depth
of 5 mm and allowed to solidify. The microbial suspension
(1.2×108 CFU/ml) (0.5 McFarland Nephelometery Standards)
was streaked over the surface of media using a sterile cot-
ton swab (15 min at 180°C) to ensure confluent growth of
the organisms. The tested compounds were dissolved in
N,N-dimethylformamide (DMF) and diluted with ethanol to
obtain a solution of 100–500 µg/ml concentration. The discs
measuring 6.25 mm in diameter (Whatman no. 1 filter paper)
were impregnated with the prepared solution of compounds
3a–h and 4a–e, and placed on Muller-Hinton agar media pre-
viously inoculated with bacterial suspension. The inhibition
zones as a criterion for antimicrobial activity were measured
at the end of an incubation period of 24 h at 37°C. The results
of these evaluations are given in Table 1. Streptomycin was
chosen as a standard drug at a concentration of 10 µg/ml.
Streptomycin is an antibiotic that inhibits both Gram-positive
and Gram-negative bacteria and is, therefore, a useful broad
spectrum antibiotic (Table 1).
Experimental
Melting points were recorded on an Electrothermal type 9100 melt-
ing point apparatus and were not corrected. The H NMR spectra
1
were recorded in CDCl3 at 100 MHz on a Bruker AC 100 spectrom-
eter. Chemical shifts are reported in ppm downfield from TMS as
internal standard; coupling constants J are given in Hertz. The IR
spectra were recorded in KBr pellets. The mass spectra were scanned
on a Varian Mat CH-7 at 70 eV. Elemental analysis was performed on
a Thermo Finnigan Flash EA microanalyzer.
General procedure for the synthesis of 3-aryl-7-
chloro-1,5-dimethyl-1H-pyrimido[4,5-e][1,3,4]
oxadiazines 3a–h
To a magnetically stirred solution of 5-bromo-2-chloro-6-methyl-4-
(1-methylhydrazino)pyrimidine (2, 1 mmol, 0.25 g) and an appropri-
ate acyl halide (1 mmol) in dry acetonitrile (20 ml), K2CO3 (2 mmol,
0.28 g) was added and the mixture was stirred at room temperature
for 1 h. Then, the mixture was refluxed for 6–7 h and the progress
of the reaction was monitored by TLC using petroleum ether/ethyl
acetate (7:3). After the completion of the reaction the mixture was
cooled and the solvent was removed under reduced pressure. Water
(5 ml) was added to the residue and the mixture was neutralized with
0.1 m HCl solution. The crude solid was filtered and crystallized
from aqueous ethanol.
It can be concluded from the data in Table 1 that compounds
3d and 3g show the highest sensitivity against E. coli and are
moderately sensitive against other organisms. Compound 3e
exhibits the highest activity against B. subtilis, whereas com-
pound 4a shows activity against S. aureus. All the other com-
pounds were found to exhibit slight to moderate sensitivity
against the mentioned organisms.
7-Chloro-1,5-dimethyl-3-phenyl-1H-pyrimido[4,5-e][1,3,4]
oxadiazine (3a) This compound was obtained as yellow nee-
dles; yield 70%; m.p. 156–157°C; 1H NMR: δ 2.22 (s, 3H, CH3-
pyrimidine), 3.21 (s, 3H, CH3-N), 7.1–7.8 (m, 5H, phenyl); IR: ν
3010, 2950, 1154 cm-1 (C-O); MS: (m/z) 274 (M+), 276 (M++2).
Anal. calcd. for C13H11ClN4O: C, 56.84; H, 4.04; N, 20.39. Found:
C, 55.48; H, 3.20; N, 21.97.
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Pyrimido[4,5-e][1,3,4]οxadiazines 51
Table 1 Antibacterial activity data for compounds 3a–h and 4a–e.
Compound
Gram-positive bacteria
Gram-negative bacteria
Staphylococcus
Bacillus subtilis
Escherichia coli
Pseudomonas aeruginosa
aureus PTCC 1074
PTCC 1365
HB101 BA 7601C
PTCC 1431
3a
3b
3c
3d
3e
3f
3g
3h
4a
4b
4c
4d
14 (+)
10 (-)
11 (-)
13 (+)
11 (-)
10 (-)
12 (+)
12 (+)
15 (++)
9 (-)
11 (-)
11 (-)
11 (-)
12 (+)
15 (++)
11 (-)
10.5 (-)
12 (+)
12 (+)
11 (-)
9 (-)
10 (-)
12 (+)
12 (+)
15 (++)
12 (+)
11 (-)
16 (++)
12 (+)
12 (+)
11 (-)
12 (+)
12 (+)
11 (-)
13
11 (-)
10.5 (-)
12 (+)
12 (+)
10 (-)
11 (-)
10.5 (-)
12 (+)
13 (+)
11 (-)
8 (-)
9 (-)
10 (-)
10 (-)
13
13 (+)
11 (-)
10
8 (-)
9 (-)
15
4e
Streptomycin
(standard)
Zones of inhibition are given in millimeters (mm). (++) Highly sensitive, (+) moderately sensitive, (-) slightly sensitive.
3015, 2965, 1101 cm-1 (C-O); MS: (m/z) 319 (M+), 321 (M++2).
7-Chloro-3-(2-chlorophenyl)-1,5-dimethyl-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (3b) This compound was obtained as yellow
needles; yield 60%; m.p. 165–166°C; 1H NMR: δ 2.21 (s, 3H, CH3-
pyrimidine), 3.20 (s, 3H, CH3-N), 7.3–7.7 (4H, m, phenyl); IR: ν
3020, 2980, 1207 cm-1 (C-O); MS: (m/z) 308 (M+), 310 (M++2), 312
(M++4). Anal. calcd. for C13H10Cl2N4O: C, 50.51; H, 3.26; N, 18.12.
Found: C, 50.42; H, 3.19; N, 18.03.
Anal. calcd. for C13H10ClN5O3: C, 48.84; H, 3.15; N, 21.91. Found:
C, 48.89; H, 3.18; N, 21.98.
7-Chloro-1,5-dimethyl-3-(4-nitrophenyl)-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (3g) This compound was obtained as yellow
needles; yield 70%; m.p. 208–210°C; 1H NMR: δ 2.23 (s, 3H, CH3-
pyrimidine), 3.22 (s, 3H, CH3-N), 7.91 (d, J=9 Hz, 2H, phenyl) 8.23
(d, J=9 Hz, 2H, phenyl); IR: ν 3045, 2925, 1107 cm-1 (C-O); MS:
(m/z) 319 (M+), 321 (M++2). Anal. calcd. for C13H10ClN5O3: C,
48.84; H, 3.15; N, 21.91. Found: C, 48.94; H, 3.17; N, 22.02.
7-Chloro-3-(3-chlorophenyl)-1,5-dimethyl-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (3c) This compound was obtained as yellow
needles; yield 65%; m.p. 172–173°C; 1H NMR (CDCl3, ppm) δ 2.21
(s, 3H, CH3-pyrimidine), 3.20 (s, 3H, CH3-N), 7.2–7.6 (4H, m, phe-
nyl); IR: ν 3020, 2940, 1202 cm-1 (C-O); MS: (m/z) 308 (M+), 310
(M++2), 312 (M++4). Anal. calcd. for C13H10Cl2N4O: C, 50.51; H,
3.26; N, 18.12. Found: C, 50.40; H, 3.20; N, 18.07.
7-Chloro-1,5-dimethyl-3-(4-methylphenyl)-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (3h) This compound was obtained as yellow
needles; yield 60%; m.p. 150–151°C; 1H NMR: δ 2.23 (s, 3H, CH3-
pyrimidine), 2.40 (s, 3H, CH3-phenyl), 3.21 (s, 3H, CH3-N), 7.33 (d,
J=7 Hz, 2H, phenyl), 7.82 (d, J=7 Hz, 2H, phenyl); IR: ν 3015, 2930,
1152 cm-1 (C-O); MS: (m/z) 288 (M+), 290 (M++2). Anal. calcd. for
C14H13ClN4O: C, 58.24; H, 4.54; N, 19.40. Found: C, 58.32; H, 4.60;
N, 19.61.
7-Chloro-3-(4-chlorophenyl)-1,5-dimethyl-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (3d) This compound was obtained as yel-
1
low needles; yield 50%; m.p. 175–176°C; H NMR: δ 2.22 (s, 3H,
CH3-pyrimidine), 3.21 (s, 3H, CH3-N), 7.33 (d, J=8 Hz, 2H, phe-
nyl), 7.74 (d, J=8 Hz, 2H, phenyl); IR: ν 3060, 2950, 1153 cm-1
(C-O); MS: (m/z) 308 (M+), 310 (M++2), 312 (M++4). Anal. calcd.
for C13H10Cl2N4O: C, 50.51; H, 3.26; N, 18.12. Found: C, 50.60; H,
3.23; N, 18.15.
General procedure for the synthesis of 7-substituted-1,5-dim-
ethyl-3-phenyl-1H-pyrimido[4,5-e][1,3,4]oxadiazines 4a–e
A
mixture of 7-chloro-1,5-dimethyl-3-phenyl-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (3a, 1 mmol, 0.27 g) and appropriate secondary
amine (4a–e, 2.2 mmol) in ethanol (5 ml) was heated under reflux for
approximately 2–3 h. After cooling to room temperature, water was
added to the solution. The resulting solid was collected by filtration,
washed with water and dried.
3-(4-Bromophenyl)-7-chloro-1,5-dimethyl-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (3e) This compound was obtained as yellow
needles; yield 75%; m.p. 178–180°C; 1H NMR: δ 2.19 (s, 3H, CH3-
pyrimidine), 3.19 (s, 3H, CH3-N), 7.51–7.72 (AB quartet, 4H, phe-
nyl); IR: ν 3030, 2930, 1154 cm-1 (C-O); MS: (m/z) 352 (M+), 354
(M++2), 356 (M++4). Anal. calcd. for C13H10BrClN4O: C, 44.16; H,
2.85; N, 15.84. Found: C, 44.01; H, 2.81; N, 15.79.
1,5-Dimethyl-7-morpholino-3-phenyl-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (4a) This compound was obtained as yel-
1
low plates; yield 70%; m.p. 189°C; H NMR: δ 2.18 (s, 3H, CH3-
7-Chloro-1,5-dimethyl-3-(3-nitrophenyl)-1H-pyrimido[4,5-e]
[1,3,4]oxadiazine (3f) This compound was obtained as yellow
needles; yield 50%; m.p. 180–181°C; 1H NMR: δ 2.24 (s, 3H, CH3-
pyrimidine), 3.23 (s, 3H, CH3-N), 7.2–8.5 (m, 4H, phenyl); IR: ν
pyrimidine), 3.21 (s, 3H, CH3-oxadiazine), 3.70 (m, 8H, CH2),
7.3–7.8 (m, 5H, phenyl); IR: ν 3945, 2930, 1154 cm-1 (C-O); MS:
(m/z) 325 (M+). Anal. calcd. for C17H19N5O2: C, 62.75; H, 5.89; N,
21.52. Found: C, 62.43; H, 5.50; N, 21.11.
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52 M. Bakavoli et al.
1,5-Dimethyl-7-piperidino-3-phenyl-1H-pyrimido[4,5-e][1,3,4]
oxadiazine (4b) This compound was obtained as yellow plates;
yield 75%; m.p. 180°C; 1H NMR: δ 1.60 (m, 6H, CH2), 2.19 (s, 3H,
CH3-pyrimidine), 3.23 (s, 3H, CH3-oxadiazine), 3.66 (m, 4H, CH2),
7.3–7.9 (m, 5H, phenyl); IR: ν 3055, 2940, 1155 cm-1 (C-O); MS:
(m/z) 323 (M+). Anal. calcd. for C18H21N5O: C, 66.85; H, 6.55; N,
21.66. Found: C, 66.75; H, 6.50; N, 21.32.
Barbaric, M.; Kraljvic, S.; Grce, M.; Zorc, B. Novel 1,2,5-oxadiaz-
ine derivatives – synthesis and in vitro biological studies. Acta
Pharm. 2003, 53, 175–186.
Berkowitz, P. T.; Long, R. A.; Dea, P.; Robins, R. K.; Mathews, T. R.
Synthesis and antimicrobial activity of certain 6H-1,2,4-oxadiaz-
in-3(2H)-one. J. Med. Chem. 1977, 20, 134–138.
Collins, A. H. Microbiological Methods; Butterworth: London,
1976.
Cruickshank, R.; Duguid, J. P.; Marion, B. P.; Swain, R. H. A.
Medicinal Microbiology; Churchill Livingstone: London, 1975;
Vol. II, pp. 196–202.
Elliot, A. J.; Gibson, M. S. A new synthesis of 4H-1,3,4-benzoxadi-
azines. J. Chem. Soc. Perkin Trans. 1972, 1, 2915–2917.
Elliot, A. J.; Gibson, M. S. Hydrazides and thiohydrazides as sources
of condensed oxadiazines and thiadiazines, including novel
azo derivatives based on dithizone. J. Org. Chem. 1980, 45,
3677–3681.
1,5-Dimethyl-7-(4-methylpiperazino)-3-phenyl-1H-
pyrimido[4,5-e][1,3,4]oxadiazine (4c) This compound was ob-
tained as yellow plates; yield 70%; m.p. 177°C; H NMR: δ 2.18
(s, 3H, CH3-pyrimidine), 2.34 (s, 3H, CH3-piperazine), 2.43 (t, 4H,
CH2), 3.22 (s, 3H, CH3-oxadiazine), 3.72 (t, 4H, CH2), 7.4–7.9 (m,
5H, phenyl); IR: ν 3035, 2930, 1150 cm-1 (C-O); MS: (m/z) 338 (M+).
Anal. calcd. for C18H22N6O: C, 63.89; H, 6.55; N, 24.83. Found: C,
63.82; H, 6.44; N, 24.66.
1
Freeman, J. P.; Kassner, J. A.; Grabiak, R. C. Heterocyclic N-oxides
as synthetic intermediates. Conversion of 1,3,4-oxadiazin-6-one
4-oxides to substituted butenolides. J. Org. Chem. 1975, 40,
3402–3407.
Gaozza, C. H.; Lamdan, S. Intramolecular cyclization of N′-
chloroacetylsalicylhydrazide. J. Heterocycl. Chem. 1970, 7,
927–930.
Gravestock, M. B. Oxadiazines and related compounds. Eur. Pat.
Appl. EP 265169, 1987 (Chem. Abstr. 1988, 109, 110e).
Khan, K. M.; Rahat, S.; Choudhary, M. I.; Rahman, A.; Ghani, U.;
Perveen, S. Effect of supramolecular inclusion on the 1,2-rear-
rangement of free radicals. Helv. Chim. Acta 2002, 85, 559–570.
Kim, H. S.; Kurasawa, Y. Synthesis of 1,3,4-thiadiazines and 1,3,4-
oxadiazines. Heterocycles 1998, 49, 557–586.
Kornet, M. J. Synthesis and anticonvulsant activity of 2-aryl-3,4-
dialkyltetrahydro-1,3,4-oxadiazines and 2-aryl-3,4-dialkyltetra-
hydro-1,3,4-oxadiazin-5-ones. J. Heterocycl. Chem. 1996, 33,
2047–2049.
7-(4-Ethylpiperazino)-1,5-dimethyl-3-phenyl-1H-pyrimido[4,5-
e][1,3,4]oxadiazine (4d) This compound was obtained as yellow
plates; yield 70%; m.p. 190°C; 1H NMR: δ 1.11 (t, J=5 Hz, 3H, CH3
of ethyl), 2.17 (s, 3H, CH3-pyrimidine), 2.41 (t, 6H, CH2), 3.21 (s,
3H, CH3-oxadiazine), 3.74 (t, 4H, CH2), 7.4–7.9 (m, 5H, phenyl); IR
(KBr disc) ν 3055, 2950, 1140 cm-1 (C-O), ms (m/z) 352 (M+). Anal.
calcd. for C19H24N6O: C, 64.75; H, 6.86; N, 23.85. Found: C, 64.69;
H, 6.80; N, 23.71.
1,5-Dimethyl-3-phenyl-7-pyrrolidino-1H-pyrimido[4,5-e][1,3,4]
oxadiazine (4e) This compound was obtained as yellow plates;
yield 79%; m.p. 168°C; 1H NMR: δ 1.93 (t, J=4 Hz, 4H, CH2), 2.21
(s, 3H, CH3-pyrimidine), 3.24 (s, 3H, CH3-oxadiazine), 3.51 (t, 4H,
CH2), 7.4–7.8 (m, 5H, phenyl); IR: ν 3065, 2940, 1155 cm-1 (C-O);
MS: (m/z) 309 (M+). Anal. calcd. for C17H19N5O: C, 66.00; H, 6.19;
N, 22.64. Found: C, 65.79; H, 6.12; N, 22.50.
Mourad, A. E.; Hassan, A. A.; Aly, A. A.; Mohamed, N. K.; Ali, B.
A. Rhodanine in fused-heterocycles syntheses. Phosphor. Sulfur
Silicon 2007, 182, 321–331.
References
Robinson, R. P.; Donahue, K. M. Synthesis of N-alkoxycarbonyl and
N-carboxamide derivatives of anti-inflammatory oxindoles. J.
Heterocycl. Chem. 1994, 31, 1541–1544.
Bakavoli, M.; Nikpour, M.; Rahimizadeh, M. New access to
thiazolo[4,5-d]pyrimidine derivatives. J. Heterocycl. Chem.
2006, 43, 1327–1329.
Rosling, A.; Klika, K.; Fulop, F.; Sillanpaa, R.; Mattinen, J. The con-
formational preference of some tetrahydropyrrolo[1,2-d][1,3,4]
oxadiazine derivatives as studied by NMR spectroscopy and
X-ray analysis. Heterocycles 1999, 51, 2575–2588.
Shawali, A. S.; Hassaneen, H. M. Aryl alkanehydrazonates and
their thio analogs. Synthesis of some 2-alkyl derivatives of 4H-
1,3,4-benzoxadiazines and 4H-1,3,4-benzothiadiazines. Bull.
Chem. Soc. Jpn. 1977, 50, 2827–2828.
Shindy, H. A.; El-Maghraby, M. A.; Eissa, F. M. Synthesis, photo-
sensitization and antimicrobial activity of certain oxadiazine cya-
nine dyes. Dyes Pigm. 2006, 70, 110–116.
Trepanier, D. L.; Spramanis, V.; Tharpe, D. S.; Krieger, P. E. 5,6-
Dihydro-4H-1,3,4-oxadiazines. J. Heterocycl. Chem. 1965, 2,
403–409.
Bakavoli, M.; Nikpour, M.; Rahimizadeh, M. Design and synthesis of
pyrimido[4,5-b][1,4]benzothiazinederivatives,aspotent15-lipox-
ygenase inhibitors. Bioorg. Med. Chem. 2007, 15, 2120–2126.
Bakavoli,M.;Sadeghian,H.;Tabatabaei,Z.;Rezaei,E.;Rahimizadeh,
M.; Nikpour, M. SAR comparative studies on pyrimido[4,5-b]
[1,4] benzothiazine derivatives as 15-lipoxygenase inhibitors
using ab initio calculations. J. Mol. Mod. 2008a, 14, 471–478.
Bakavoli, M.; Rahimizadeh, M.; Shiri, A.; Eshghi, H.; Nikpour, M.
Facile synthesis of 2-anilino-pyrimido[4,5-e][1,3,4] thiadiazines.
Heterocycles, 2008b, 75, 1745–1748.
Bakavoli, M.; Bagherzadeh, G.; Vaseghifar, M.; Shiri, A.; Pordeli,
P. Iodine catalyzed synthesis and antibacterial evaluation of
thieno[2,3-d]pyrimidine derivatives. J. Chem. Res. 2009, 653–655.
Bakavoli, M.; Bagherzadeh, G.; Vaseghifar, M.; Shiri, A.; Pordel, M.;
Mashreghi, M.; Pordeli, P.;Araghi, M. Molecular iodine promoted
synthesis of new pyrazolo[3,4-d]pyrimidine derivatives as poten-
tial antibacterial agents. Eur. J. Med. Chem. 2010, 45, 647–650.
Received April 18, 2011; accepted May 5, 2011
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