Reactions of 2-cyano-2-nitrosomethylbenzthiazole: One-pot synthesis of new polyfunctional pyrazine derivatives

Article abstract of DOI:10.1080/10426500214131

2-Cyano-2-nitrosomethylbenzthiazole reacts with some active methylene and nucleophile derivatives to yield new fused and isolated polyfunctional pyrazine, -[1,2,4]triazine, -[1,4,5]benzoxadiazepin, -[1,4, 5]benzothiadiazepine, [1,4,5]benzotriazepine, -triazole and -triazolo-[3,2-c]triazine derivatives in one-pot reaction. The structures were based on IR, MS, and ¹H NMR spectra and elemental data.

Full text of DOI:10.1080/10426500214131

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Reactions of 2-Cyano-2-nitrosomethylbenzthiazole:
One-Pot Synthesis of New Polyfunctional Pyrazine
Derivatives
Fawi M. Abd El Latif a , Eman A. Ei Rady a & Mohamed A. Khalil a
a Chemistry Department, Faculty of Science, South Valley University, Aswan, Egypt
Version of record first published: 27 Oct 2010.
To cite this article: Fawi M. Abd El Latif , Eman A. Ei Rady & Mohamed A. Khalil (2002): Reactions of 2-Cyano-2-
nitrosomethylbenzthiazole: One-Pot Synthesis of New Polyfunctional Pyrazine Derivatives, Phosphorus, Sulfur, and Silicon and
the Related Elements, 177:10, 2497-2505
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2497–2505
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DOI: 10.1080/10426500290110658
REACTIONS OF
2-CYANO-2-NITROSOMETHYLBENZTHIAZOLE:
ONE-POT SYNTHESIS OF NEW POLYFUNCTIONAL
PYRAZINE DERIVATIVES
Fawi M. Abd El Latif, Eman A. Ei Rady,
and Mohamed A. Khalil
Chemistry Department, Faculty of Science, South Valley
University, Aswan, Egypt
(Accepted December 31, 2001)
2-Cyano-2-nitrosomethylbenzthiazole reacts with some active methyl-
ene and nucleophile derivatives to yield new fused and isolated
polyfunctional pyrazine, -[1,2,4]triazine, -[1,4,5]benzoxadiazepin, -[1,4,
5]benzothiadiazepine, [1,4,5]benzotriazepine, -triazole and -triazolo-
[3,2-c]triazine derivatives in one-pot reaction. The structures were
based on IR, MS, and 1H NMR spectra and elemental data.
Keywords: -[1,4,5]Benzothiadiazepine; 2-cyano-2-nitrosomethylbenzo-
thiazole; benzothia[2,3-a]pyrazine
Azolylacetonitriles are readily obtainable compounds that have been
extensively utilized as intermediates in heterocyclic synthesis.1–4 In
connection with our interest in the synthesis of condensed azines,5–10
we report herein a new and simple route for the synthesis of benzthia-
zole derivatives of polyfunctional pyrazine and other azine compounds
that may have pharmaceutical effects.
Thus, nitrozation of 2-cyanomethylbenzthiazole by sodium ni-
trite in ethanolic hydrochloric acid mixture yielded the 2-cyano-2-
nitrosomethylbenzthiazole 1 in quantitative yield. The MS of 1 showed
m/z at 203 (M+, 70), 173 (M NO, 100), 145 (173-N2, 71). The nitroso
compound 1 reacts readily with malononitrile 2a, ethyl cyanoacetate 2b
and benzoylacetonitrile 2c in boiled ethanol containing triethylamine
to yield the corresponding benzothiazolo[2,3-a]pyrazine derivatives
4a–c in 75–80% yields. The formation of 4 was assumed to proceed via
Address correspondence to Fawi M. Abd Latif, Chemistry Department, Faculty of
Science, South Valley University, Aswan, Egypt. E-mail: Latif72001@yahoo.com
2497

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F. M. Abd El Latif et al.
SCHEME 1
the intermediate 3, which cyclizes to 4, (c. f. Scheme 1). The IR spec-
1
trum of 4b showed bands at 3125, 2215, 1720 cm due to NH, CN,
1
and CO groups. The MS of 4b showed m/z at 298 (M+, 10) and the H
NMR spectrum (DMSO) of 4b showed triplet and quartet at 1.2 and
4.2 ppm assignable to the protons of the ester, and at 7.1–7.9 due to NH
and aromatic protons. However, the nitroso compound 1 reacts directly
with cyanoacetamide 5a in ethanol containing triethylamine at reflux
temperature to yield a product its mass spectrum showed m/z = 269

Reactions of 2-Cyano-2-nitrosomethylbenzthiazole
2499
(M+, 15). Several isomeric structures (7–11) seemed possible for this
product (Scheme 1). Structure 11 was preferred over structure 9 based
on mass and IR spectra, structure 9, however assumed to be formed by
elimination of amoina from its precursor 8. On the other hand, IR spec-
trum of 11a revealed characteristic absorption bands at 3345, 3218,
1
2215, and 1690 cm assigned for NH2, NH, CN, and C O groups, re-
spectively. If the product was 7, lower absorption frequencies for amidic
C O should observed, and an expected hydrogen bond would revealed
1
a broad NH absorption band. The H NMR (DMSO) of 11a revealed
signals at 7.1–7.8 assigned to aromatic, NH and at 8.2 ppm due to
NH2 protons. In analogy, compound 1 reacts with 5b to give 11b.
The reactivity of the nitroso function in 1 was also explored via its
reaction with some laboratory available nucleophiles reagents. Thus,
the reaction with thiourea 12a and urea 12b yielded the substituted
[1,2,4]triazines 16a,b. Again, two theoretical possible structures 14 and
16 can be considered (c.f. Scheme 2). Structure 16 was suggested for
SCHEME 2

2500
F. M. Abd El Latif et al.
this product based on the MS of 16a which showed m/z at 263 (M +
2, 15), 245 (M NH2, 14), 229 (M S, 11), 213 (M S NH2, 15), 203
(34), and 173 (53%). The IR spectrum of 16a revealed bands at 3325,
1
3215 cm (NH2, NH) and IR spectrum of 16b showed characteristic
1
absorption bands at 3325, 3215, and 1685 cm for NH2, NH, and
CO groups. However, the nitroso compound 1 reacted with 17a,b to
afford substituted triazolo[3,2-c][1,2,4]triazine 19a and pyrazolo[3,2-
c][1,2,4]triazine 19b via condensation intermediate 18, which then cy-
clizes to 19. The 1H NMR (DMSO) spectrum of 19a revealed signals at
7.1–7.9 and 8.1 ppm due to the aromatic and NH2 protons. Similarly,
the nitroso compound 1 reacts with hydrazine hydrate 20a, phenylhy-
drazine 20b to give 5-amino-4-(benzthiazole-2-yl)-1,2,3-triazole 22a,b
(c.f. Scheme 3). The IR spectrum of 22a showed bands at 3345 and 3125
1
cm assignable to NH2 and NH groups, with the disappearance of the
characteristic absorption due to cyano function. The MS of 22a showed
m/z at 219 (M + 2, 3), 217 (M+, 5), 203 (M N, 8), 177 (M N CN, 7),
173 (M N2 NH2), and 146 (M N2 NH2 HCN, 13%).
SCHEME 3

Reactions of 2-Cyano-2-nitrosomethylbenzthiazole
2501
SCHEME 4
Finally, o-aminothiophenol 23a, o-aminophenol 23b and o-phenyl-
enediamine 23c reacted easily with compound 1 in refluxing ethanol
containing triethylamine to yield the new 2-amino-3-(benzthiazole-
2-yl)-[1,4,5]thiadiazepine 25a, -[1,4,5]-oxadiazepine 25b and -[1,4,5]-
triazepine 25c in 65–75 % yields. The fused tetracyclic structure 27
1
was ruled out based on the IR, H NMR, MS and elemental analysis
1
(Scheme 4). The IR spectra of 25 revealed bands at 3325–3245 cm
attributed to the NH2 group. The MS of 25a showed m/z at 311
(M + 1, 93), 294 (M NH2, 5), 282 (M N2, 82), 268 (M N2 N, 22), 248
(M N NH2 S, 76), and 173 (100%). The MS of 25c showed m/z at 294
(M + 1, 40), 264 (M H N2, 30), 248 (M N2 H NH2, 5), and 173 (65%).
EXPERIMENTAL
All melting points are uncorrected. The IR spectra were recorded (KBR,
= cm 1) on a Shimadzu 408 and a Pye Unicam Spectrophotometer.
1H NMR spectra (DMSO-d6 = ppm) were recorded on a Varian EM

2502

Reactions of 2-Cyano-2-nitrosomethylbenzthiazole
2503
390 90 MHz spectrometer. TMS was used as internal reference. Mass
spectra were recorded on a mass spectrometer MS 9 (AET) EI Mode.
Elemental analysis were carried out at Microanalytical Center, Cairo
University, Egypt.
2-Cyanomethylbenzthiazole was prepared according to the proce-
dure described in literature.11
2-Cyano-2-nitrosomethylbenzothiazole (1)
2-Cyanomethylbenzothiazole (1.7 g, 0.01 mol) was dissolved in a mix-
ture of 10 ml of hydrochloric acid and 30 ml of ethanol, then cooled in
an ice bath at 0 C. A cold solution of sodium nitrite (2.07 g, 0.03 mol)
was added dropwise throughout a period of 30 min. The reaction mix-
ture was allowed to stand for 24 h in a refrigerator; the solid product so
formed was filtered, washed with water, dried, and recrystallized from
ethanol to give pale yellow (Table I).
General Procedure for the Synthesis of 2.10-Dicyano-
3-imino-benzthiazolo[2,3-a]pyrazine (4a) and its
Derivative (4b)
A mixture of 1 (0.5 g, 0.01 mol), malononitrile 2a (0.16 g, 0.01 mol), and
0.1 ml of triethylamine was refluxed in 30 ml of absolute ethanol for
2 h. The colorless crystalls (4a) which deposit during the reaction are
isolated by vacuum filtration, washed with methanol, and recrystallized
from ethanol. The nitroso compound 1 reacted analogously with ethyl
cyanoacetate 2b (0.28 g, 0.01 mol) to give 4b. The spectral, physical,
and elemental analytical data are listed in Table I.
General Procedure for the Synthesis of 2-Amino-3-
(benzthiazole-2-yl)-5-cyano-1,6-dihydropyrazin-6-one
(11a) and its 6-Thione Isomer (11b)
A mixture of 1 (0.5 g, 0.01 mol), cyanooacetamide 2a (0.2 g, 0.01 mol),
and 0.1 ml of triethylamine was refluxed in 40 ml of absolute ethanol for
5 h. The solution was concentrated under reduce pressure. The residue
was treated with methanol and the crude product 11a was filtered,
washed with methanol, and recrystallized from ethanol. Similarly, the
nitroso 1 was reacted with cyanothioacetamide 5b (0.25 g, 0.01 mol)
under the same reaction conditions to give the corresponding pyrazine-
6-thione 11b. The spectral, physical, and elemental analytical data are
listed in Table I.

2504
F. M. Abd El Latif et al.
General Procedure for the Synthesis of 2-Amino-3-
(benzthiazole-2-yl)-1,6-dihydropyrazine-6-thione (16a)
and its Derivative (16b)
A mixture of 1 (0.5 g, 0.01 mol), thiourea 12a (0.19 g, 0.01 mol), and
0.1 ml of triethylamine was refluxed in 30 ml of absolute ethanol for
6 h. The solution was concentrated under reduce pressure and the solid
product 16a so formed was filtered, washed with ethanol, and recrystal-
lized from ethanol. The nitroso compound 1 reacted analogously with
urea 12b (0.14 g, 0.01 mol) to give 16b (Table I).
General Procedure for the Synthesis of 5-Amino-6-
(benzthiazole-2-yl)[1,2,4]triazolo[3,2-c][1,2,4]triazine
(19a) and 7-Phenylpyrazolo[3,2-c][1,2,4]triazine (19b)
A mixture of 1 (0.5 g, 0.01 mol), 5-amino-1H-1,2,4-triazole 17a (0.20 g,
0.01 mol), and 0.1 ml of triethylamine was refluxed in 30 ml of ab-
solute ethanol for 10 h. The solution was concentrated under reduce
pressure and the solid product 19a so formed was filtered, washed,
with ethanol and recrystallized from methanol. The nitroso compound
1 reacted analogously with 5-amino-3-phenyl-1H-pyrazole 17b (0.39 g,
0.01 mol) to give the corresponding title compounds 19b. The spectral,
physical, and elemental analytical data are listed in Table I.
General Procedure for the Synthesis of 5-Amino-
4-(benzthiazole-2-yl)1,2,3-triazole (22a) and its
Derivative (22b)
A mixture of 1 (0.5 g, 0.01 mol), hydrazine hydrate 20a (0.12 g, 0.01 mol),
and 0.1 ml of triethylamine was refluxed in 30 ml of absolute ethanol
for 2 h. The colorless crystals formed during the reaction were filtered,
washed with methanol, and recrystallized from ethanol. The nitroso
compound 1 reacted analogously with phenylhydrazine 20b (0.27 g,
0.01 mol) to give the corresponding title compound 22b. The spectral,
physical, and elemental analytical data are listed in Table I.
General Procedure for the Synthesis of 2-Amino-3-
(benzthiazole-2-yl)[1,4,5]benzothiadiazepine (25a),
-[1,4,5]Benzoxadiazepine (25b) and
-[1,4,5]Benzotriazepine (25c)
A mixture of 1 (0.5 g, 0.01 mol), o-aminothiophenol 23a (0.30 g,
0.01 mol), and 0.1 ml of triethylamine was refluxed in 30 ml of absolute

Reactions of 2-Cyano-2-nitrosomethylbenzthiazole
2505
ethanol for 3 h. The green crystalls separated during reflux were col-
lected by vacuum filtration, washed with methanol, and recrystal-
lized from DMF. The nitroso compound 1 reacted analogously with
o-aminophenol 23b (0.27 g, 0.01 mol) and o-phenylenediamine 23c
(0.27 g, 0.01 mol) to give the title compounds 25b,c. The spectral, phys-
ical, and elemental analytical data are listed in Table I.
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