Part 1: Synthesis of polyfused heterocyclic systems derived from 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazepine-6,8- dione

Article abstract of DOI:10.1080/10426500214876

3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6,8- dione (1) was condensed with o-aminothiophenol, 2-amino-ethanol or cystamine to afford compounds 2-4 respectively. Treatment of compound 1 with dimethylthiomethylenemalononitrile yielded the corresponding pyrano[3,2-f][1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine derivative 5. 7-[5-Amino-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4] triazolo[3,4-b][1,3,4]thiadiazepine-6,8-dione (6) was obtained by treating compound 1 with CS₂ and chloroacetonitrile. Thiation of compound 1 gave the corresponding thioanalog 7, which in turn was condensed with malononitrile to give 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6-one- 8-ylidenemalononitrile (8). On treating compound 8 with benzaldehyde or p-nitrobenzaldehyde, pyrano[1,2,4]triazolo[1,3,4]thiadiazepin derivatives 9a,b, respectively, were obtained. Compound 8 was treated with CS₂ and methyl iodid to give the corresponding dithiomethyl-methylene derivative 10 which was subjected to react with aniline to give pyrido[1,2,4]triazolo[1,3,4]thiadiazepine derivative 11. Compound 8 was treated with 3-aminopyridine, o-aminothiophenol, or o-phenylenediamene to yield compounds 12 and 13a,b respectively. Finally, tertiary amines or activated phenols were condensed with compound 8 to yield compounds 14 and 15a,b respectively.

Full text of DOI:10.1080/10426500214876

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Phosphorus, Sulfur, and Silicon and the Related
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Part 1: Synthesis of Polyfused Heterocyclic
Systems Derived From 3-Phenyl-5,6,7,8-
tetrahydro[1,2,4]triazolo[3,4- b ]
[1,3,4]thiadiazepine-6,8-dione
O. A. Abd Allah a
a Chemistry Department, Faculty of Science , South Valley University , Sohag, Egypt
Published online: 27 Oct 2010.
To cite this article: O. A. Abd Allah (2002) Part 1: Synthesis of Polyfused Heterocyclic Systems Derived From 3-Phenyl-5,6,7,8-
tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione, Phosphorus, Sulfur, and Silicon and the Related Elements,
177:12, 2871-2881, DOI: 10.1080/10426500214876
To link to this article: http://dx.doi.org/10.1080/10426500214876
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2871–2881
C
Copyright 2002 Taylor & Francis
1042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290146910
PART 1: SYNTHESIS OF POLYFUSED
HETEROCYCLIC SYSTEMS DERIVED FROM
3-PHENYL-5,6,7,8-TETRAHYDRO[1,2,4]TRIAZOLO-
[3,4-b][1,3,4]THIADIAZEPINE-6,8-DIONE
O. A. Abd Allah
Chemistry Department, Faculty of Science, South Valley
University, Sohag, Egypt
(Received January 27, 2002; accepted April 2, 2002)
3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-
6,8-dione (1) was condensed with o-aminothiophenol, 2-amino-ethanol
or cystamine to afford compounds 2–4 respectively. Treatment of
compound 1 with dimethylthiomethylenemalononitrile yielded the
corresponding pyrano[3,2-f][1,2,4]triazolo[3,4-b]-[1,3,4]thiadiazepine
derivative 5. 7-[5-Amino-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-
tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6,8-dione (6) was
obtained by treating compound 1 with CS2 and chloroacetoni-
trile. Thiation of compound 1 gave the corresponding thioanalog
7, which in turn was condensed with malononitrile to give 3-phenyl-
5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6-one-8-
ylidenemalononitrile (8). On treating compound 8 with benzaldehyde
or
p-nitrobenzaldehyde,
pyrano[1,2,4]triazolo[1,3,4]thiadiazepin
derivatives 9a,b, respectively, were obtained. Compound 8 was treated
with CS2 and methyl iodid to give the corresponding dithiomethyl-
methylene derivative 10 which was subjected to react with aniline
to give pyrido[1,2,4]triazolo[1,3,4]thiadiazepine derivative 11. Com-
pound 8 was treated with 3-aminopyridine, o-aminothiophenol, or
o-phenylenediamene to yield compounds 12 and 13a,b respectively.
Finally, tertiary amines or activated phenols were condensed with
compound 8 to yield compounds 14 and 15a,b respectively.
Keywords: CS2; malonyl dichloride; PTC; thiadiazepine; triazole
INTRODUCTION
It has been reported that free and fused s-triazoles constitute an im-
4
portant class of compounds with a wide biological activities.1 1,2,
4-Triazolo[3,4-b][1,3,4]thiadiazole derivatives have anti-bacterial5,6
Address correspondence to O. A. Abd Allah, Department of Chemistry, Faculty of
Science, Sohag, Egypt. E-mail: omymatif@yahoo.com
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O. A. Abd Allah
and anti-inflammatory7 activities, an interesting CNS depressant ac-
tion,8 and moderate anti-malarial and anti-tumor activities.9 The s-
triazolo(3,4-b) 1,3,4-thiadiazepines showed significant antimicrobial
properties.10,11 From this view and in the extention of our previous
work12–14 in the synthesis of free and fused s-triazole derivatives, it
is reported here in the synthesis of a new series of polyfused 1,2,4-
triazolo[3,4-b][1,3,4]thiadiazepines.
RESULTS AND DISCUSSION
3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-
6,8-dione (1) was prepared in a good yield via the reaction of
4-amino-5-phenyl-1,2,4-triazole-3-thione with malonyl dichloride and
TEA in 1:1:2 molar ratio at room temperature. The structural assign-
ment of this compound was established by elemental and spectral
analyses (Scheme 1, Table I).
Compound 1 was condensed with o-aminothiophenol, 2-amino-
ethanol, or cystamine in refluxing diphenyl ether through intermolec-
ular cyclization with the elimination of two water molecules to give the
polyfused derivatives 2–4, respectively.
Also, compound 1 was reacted in boiling DMF with dimethylthio-
methylenemalononitrile, which was prepared via the reaction of
malononitrile and CS2 with two equivalents of methyl iodid in a one-
pot reaction using liquid-liquid phase-transfer catalysis (PTC) tech-
nique [NaOH/dioxane/tetrabutylammonium bromide (TBAB)], to give
8-cyano-9-imino-7-methylthio-6-oxo-3-phenyl-5,6,8,9-tetrahydro-7H-
pyrano[3,2-f ][1,2,4]-triazolo[3,4-b][1,3,4]thiadiazepine (5) (Scheme 1,
Table I).
The 7-[5-amino-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6,8-dione (6) was obtained
through the intermediate M by treating compound 1 with CS2 and
chloroacetonitrile in one-pot reaction under PTC experimental condi-
tions [DMF/K2CO3/TBAB] (Scheme 1, Table I).
Thiation of compound 1 was performed with P2S5 in boil-
ing pyridine to give the corresponding thioanalog 3-phenyl-5,6,7,8-
tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6-oxo-8-thione (7).
The IR spectra for this compound showed the absence of a signal cor-
1
responding to C O and the presence of a C S signal at 1115 cm
(Scheme 2, Table I). The condensation of compound 7 with malonon-
itrile in boiling DMF gave the dicyanomethylene derivative 8. The
1
IR and H-nmr spectral data are consistent with the proposed struc-
tures (Scheme 2, Table I).

Synthesis of Polyfused Heterocyclic Systems
2873
SCHEME 1

2874

2875

2876

Synthesis of Polyfused Heterocyclic Systems
2877
SCHEME 2
Compound 8 was allowed to react with benzaldehyde or p-
nitrobenzaldehyde to afford the corresponding 10-cyano-9-imino-6-oxo-
3-phenyl-7-phenyl( p-nitrophenyl)-5,6,9,10-tetrahydro-7H-pyrano[3,
4-f]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepines (9a,b) respectively. The

2878
O. A. Abd Allah
reaction mechanism was postulated to proceed through the nucleophilic
attack of the active CH2 group of compound 8 at the carbonyl group
of the aromatic aldehyde producing the corresponding aldol adduct,
followed by intramolecular cyclization via the nucleophilic addition of
the formed OH group at the CN group. The IR spectra of compounds
9a,b showed the absence of a band corresponding to one CN group and
the presence of the adsorption bands corresponding to NH, CN and
C Oamidic groups at 3421, 2204 and 1650 cm 1, respectively (Scheme 2,
Table I).
Compound 8 was treated with an equimolar ratio of CS2 and double
molarity of methyl iodide to yield the corresponding s-methyl deriva-
tive 10; the latter, in turn, underwent cyclization when treated with
aniline in 1:1 or 1:2 molar ratio, affording 3,8-diphenyl-5,6,7,8,9,10-
hexahydropyrido-9-imino-7-methylthio-6-oxo[3,4-f ][1,2,4]triazolo[3,4-
b][1,3,4]-thiadiazepine (11).
The behaviour of compound 8 toward amines and phenols was in-
vestigated. The products resulted from initial attack of the nucle-
ophile at the C- of the dicyanomethylene moiety.15 Thus, compound
8 was condensed with 3-aminopyridine in a 1:3 molar ratio through
the hydrogen cyanide elimination to yield the condensed product 12.
Also treatment of compound 8 with o-aminothiophenol or o-phenylene-
diamine in refluxing DMF yielded the cyclized products 13a,b via elim-
ination of two HCN molecules. Moreover, compound 8 was allowed
to react with N,N-dimethylaniline or activated phenols, namely re-
sorcinol or o-cresol, to furnish the desired compounds 14 or 15a,b
respectively.
The structures of all products were established by using elemental
and spectral analyses.
EXPERIMENTAL
Synthesis of 3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo
[3,4-b][1,3,4]thiadiazepine-6,8-dione (1)
To a solution of 4-amino-5-phenyl-1,2,4-triazole-3-thione (0.01 mol) in
dry p-xylene (30 ml) were added triethylamine (0.02 mol) and malonyl
dichloride (0.01 mol) dropwise. The reaction mixture was stirred for 8 h
at room temperature. The reaction mixture was then filtered off, dried,
and washed with water. The precipitate was dried and crystallized from
dioxane (Table I).

Synthesis of Polyfused Heterocyclic Systems
2879
Synthesis of Compounds 2 4
General Procedure
To a solution of compound 1 (0.01 mol) in diphenyl ether (15 ml),
was added o-aminothiophenol, 2-aminoethanol, or cystamine (0.01 mol).
The reaction mixture was refluxed for 3 h, concentrated, and cooled.
The precipitate was filtered off and crystallized from suitable solvent
(Table I).
Synthesis of Compound 5
A mixture of compound 1 (0.005 mol) and dimethylthiomethylene mal-
ononitrile (0.005 mol) was refluxed in n-butanol (15 ml) untill elimina-
tion of MeSH ceased ('10 h). The reaction mixture was concentrated
and cooled. The separated solid was filtered off and crystallized from
n-butanol (Table I).
Synthesis of Compound 6
A mixture of 4 g anhydrous potassium carbonate, compound 1
(0.004 mol) in DMF (20 ml), and catalytic amount of TBAB was treated
with 0.004 mol of CS2 and stirred for 4 h at 60 C. After that, chloroace-
tonitrile (0.004 mol) was added, and the mixture was stirred for addi-
tional 16 h at 70 C. The reaction mixture was filtered, and the filtrate
was added to ice-cold water. The separated solid was filtered off and
crystallized from DMF/H2O to give compound 6 (Table I).
Synthesis of Compound 7
To a solution of compound 1 (0.01 mol) in dry pyridine (30 ml), was
added phosphorus pentasulphide (0.01 mol). The reaction mixture was
refluxed for 7 h, filtered while hot, and concentrated. The precipitate
was filtered off and crystallized from pyridine/H2O (Table I).
Synthesis of Compound 8
A mixture of compound 7 (0.01 mol), and malononitrile (0.01 mol) in
DMF (20 ml) was refluxed. The evalution of H2S was ceased ('20 h). The
reaction mixture was cooled to room temperature and poured into ice-
cold water (100 ml). The separated solid was filtered off and crystallized
from DMF/H2O (Table I).

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O. A. Abd Allah
Synthesis of Compounds 9a,b
General Procedure
A mixture of compound 8 (0.004 mol), benzaldehyde or p-nitro-
benzaldehyde (0.004 mol), and a catalytic amount of anhydrous sodium
acetate in DMF (20 ml) was refluxed for 7 h. The reaction mixture was
poured into ice-cold water (100 ml). The solid product was filtered off
and crystallized from the suitable solvent (Table I).
Synthesis of Compound 10
A mixture of 4 g anhydrous potassium carbonate, compound 8 (0.006
mol), and catalytic amount of TBAB in DMF (20 ml) was treated with
0.006 mol of CS2 and stirred for 4 h at room temperature. Methyl iodide
(0.012 mol) was added, and the mixture was stirred for an additional
4 h at room temperature. The reaction mixture was filtered off, and the
filtered was added into ice-cold water. The product was filtered off and
crystallized from DMF/H2O (Table I).
Synthesis of Compound 11
A mixture of compound 10 (0.002 mol) and aniline (0.002 mol) in DMF
(15 ml) was refluxed for 3 h. The reaction mixture was poured into ice-
cold water (100 ml) containing a few drops of dil. HCl. The separated
solid was filtered off, washed with water, dried, and crystallized from
DMF/H2O (Table I).
Synthesis of Compounds 12 15a,b
General Procedure
To a solution of compound 8 (0.002 mol) in DMF (20 ml) was added in
portions the amine or phenol (0.006 mol) in DMF (20 ml). The mixture
was refluxed for 2 h. The reaction mixture was added into ice-cold water
(100 ml). The precipitate was filtered off, dried, and crystallized from
the proper solvent (Table I).
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Synthesis of Polyfused Heterocyclic Systems
2881
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