A convenient synthesis of new [1,2,4]triazolo[3′,4′:2,3][1,3] thiazolo[4,5-b]quinoxalines

Article abstract of DOI:10.1080/104265090969018

New derivatives of 3-substitued [1,2,4]triazolo[3′,4′;2,3][1,3] triazolo[4,5-b]quinoxalines 6 have been prepared by the cyclocondensation of [1,3]thiazolo[4,5-b]quinoxaline-2(3H) one hydrazone 5 with aroyl chlorides, trimethylorthoformate, or triethylorthoacetate. Copyright Taylor & Francis LLC.

Full text of DOI:10.1080/104265090969018

Phosphorus, Sulfur, and Silicon, 181:99–104, 2006
Copyright © Taylor & Francis LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090969018
A Convenient Synthesis of New
[1,2,4]Triazolo[3ꢀ,4ꢀ:2,3][1,3]thiazolo [4,5-b]quinoxalines
M. Bakavoli
B. Reihani
M. Rahimizadeh
M. Nikpour
Department of Chemistry, Ferdowsi University of Mashhad,
Mashhad, Iran
New derivatives of 3-substitued [1,2,4]triazolo[3ꢀ,4ꢀ;2,3][1,3]triazolo[4,5-b]quin-
oxalines 6 have been prepared by the cyclocondensation of [1,3]thiazolo[4,5-
b]quinoxaline-2(3H) one hydrazone 5 with aroyl chlorides, trimethylorthoformate,
or triethylorthoacetate.
Keywords 2,3-Dichloroquinoxaline; thiazoloquinoxaline; triazolothiazoloquinoxaline
Starting from biological considerations and due to our interest in
the synthesis of polycyclic N-heterocycles,1,2 it was decided to synthe-
size [1,2,4]triazolo [3ꢀ,4ꢀ:3][1,3]thiazolo[4,5-b] quinoxaline derivatives
6(a–e). A literature search provided only one example describing this
ring system.3
We reacted Nꢀ-butyl-2(1-methylethylidene)-1-hydrazine carbothio-
mide 1 with 2,3-dichloroquinoxaline 2, similar to what had already been
reported in the literature4,5 (Scheme 1). Structure 3 was proposed for
the product characterized by its spectral data. When this compound
was subjected to diazotization at room temperature, the 3-amino moi-
ety was removed to produce 4. Subsequent treatment of this compound
with hydrazine hydrochloride produced the desired intermediate 5. The
structures assigned to compounds 4 and 5 were substantiated by their
1
spectral data (Table I). For example, the H−NMR spectrum of com-
pound 4 was devoid of the signal at δ 4.7 ppm for NH2 group of the
precursor 3, but showed further downfield a peak at 9.3 ppm for the
N-H ring proton, while 5 showed a signal at δ 10.5 ppm for the N-H
Received November 30, 2004; in final form January 11, 2005.
Address correspondence to M. Bakavoli, Department of Chemistry, School of Sciences,
Ferdowsi University, Mashhad 91775-1436, Iran. E-mail: mbakavoli@yahoo.com
99

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M. Bakavoli et al.
TABLE I Physical and Spectral Data of Thiaolo[4,5-b]quinoxalines
Reaction time Yield
M.P.
(◦C)
Entry
1
(h)
(%)
Spectral data
2
62
59–61 1H NMR: (CDCl3), 8.4 (s, 1H, NH), 7.51 (s, 1H,
NH), 3.5 (t, 2H, N-CH2); 1.5 (m, 4H, (CH2)2
(d, 6H, 2CH3), 1 (t, 3H, CH3) IR (KBr disk). v,
3250, 3200, 1640, 1200, m/z, 187 (M)
3
4
60
42
70
1H NMR: (CDCl3), 7.5–8 (m, 4H, NH, aromatic),
4.7 (s, 2H, NH2), 3.4 (t, 2H, NCH2), 1.6 (m,
4H, CH2), IR (KBr disk): v 1600, 475, 3350,
m/z, 273
4
5
3
5
80
1H NMR: (CDCl3), 7.55–8 (m, 4H, aromatic) 3.75
(t, 2H, I-Ch2); IR (KBr disk); v, 3300–3500,
100, 1650, m/z, 258 (M)
47 230–235 1H NMR: (DMSO-d6), 10.5 (s, 1H, NH, 7.8 (m,
4H, C6H4), 5.5 (s, 2H, NH2; IR (KBr disk); v
3300–3500, 3050, 1650, m/z, 217 (M)
SCHEME 1

New [1,2,4]triazolo[3ꢀ,4ꢀ:2,3][1,3]thiazolo[4,5-b]quinoxalines
101
ring proton and a broad signal at 5.5 ppm for the NH2 group, for which
both were removed on deuteration.
The interaction of the intermediate 5 with aroyl chlorides, trimethy-
lorthoformate, or triethylorthoacetate led to the tetracyclic com-
pounds 6, [1,2,4]triazolo[3ꢀ4ꢀ:2,3]thiazolo[4,5-b]quinoxalines. Assign-
ment of structure 6 is supported by their analytical and spectral data
(Table II, Scheme 1).
In conclusion, we have developed a convenient method for the con-
version of Nꢀ-butyl-2(1-methylethyliden)-1-hydraziecarbothioamide
into 3-substituded [1,2,4]triazolo[3ꢀ,4ꢀ;2,3][1,3]thiazolo[4,5-b]quino-
xalines through cyclocondensation with aroyl chlorides and orthoesters.
EXPERIMENTAL SECTION
Melting points were recorded on an Electrothermal type 9100 melting
point apparatus. The IR Spectra were obtained on a 4300 Shimadzu
Spectrometers as KBr disks. The 1H-NMR (100 MHz) spectra were
recorded on a Bruker AC 100 Spectrometer in d6 DMSO and CDCl3
solution. Mass spectra were obtained from a Varian CH-7 instrument
at 70 ev. Elemental analysis was obtained on a Thermo Finnigan Flash
EA microanalyzer.
Nꢀ-Butyl-2-(1-methyl ethyliden)-1-hydrazine-carbothioamid (1)
A mixture of n-butyl thiosemicarbazide (5.2 g, 35 mmol), and acetone
(5.1 mL, 70 mmol) in absolute ethanol (20 mL) was heated under reflux
for 2 h. The reaction mixture was then cooled to room temperature
2–3 drops of water were added, and it was allowed to stand at room
temperature and gave a while crystalline solid (4 g, 62%, yield) m.p
59–61◦C.
N-(3-Amino [1-3]thiazolo[4,5-b]quinoxaline-2-yliden)-2-
yliden)-N-butylamine (3)
To a solution of compound 1 (1.78 g, 10 mmol) in absolute ethanol (50
mL), 2,3-dichloroquinoxaline (2 g, 10 mmol) was added. The solution
was heated under reflux for 4 h then water (5 mL) was added and heat-
ing was continued for a further hour. The mixture then was allowed to
cool to room temperature. To the reaction mixture, sodium hydroxide
(5 g) in 10 mL, of H2O was added and it was stirred for 8 h. The pre-
cipitate was filtered and washed with warm water to give an orange
powder (1.23 g, 47% yield, m.p. 100–103).

102

New [1,2,4]triazolo[3ꢀ,4ꢀ:2,3][1,3]thiazolo[4,5-b]quinoxalines
103
N-(Butyl-N-[1,3]thiazolo[4,5-b]quinoxaline-2(3H)-
ylidenamine (4)
To a solution of the foregoing, compound 3 (2.73 g, 10 mmol) in conc.
HCl (37.5 mL) a solution of sodium nitrite (2.5 M, 50 mL) was added
dropwise at 0–5◦C for 2–3 h. The reaction mixture was stirred at room
temperature for a further 2 h. The solution was poured onto crushed
ice; the precipitate was filtered off and washed with warm water to give
the title compound (2.0 g, 77% yield, m.p. 86–90◦C.)
[1,3]Thiazolo[4,5-b]quinoxalin-2(3H)-one Hydrazone (5)
A solution of hydrazine monohydrochloride (0.5 g), compound 4 (0.5 g,
2 mmol), and hydrazine monohydrate (1 mL) in methanol (15 mL) was
heated under reflux for 5 h. The solution was reduced in volume under
reduced pressure, then water was added (30 mL) and the precipitate
was collected after 0.5 h as a green powder (0.2 g, 47% yield, m.p. 230–
235◦C).
Unsubstituted or 3-Substituted [1,2,4]triazolo[3ꢀ4ꢀ:2,3][1,3]-
thiazolo[4,5-b]quinoxalione (6)
Method A
Compound 5 (0.217 g, 1 mmol) and aroyl chloride (6.0 mL) was heated
under reflux for 5 h. After completion of the reaction, which was moni-
tored by TLC, an oily mixture was obtained. Sodium hydroxide (0.5 M)
was added with stirring at room temperature to pH 6–7 for 0.5 h. The
mixture then was extracted with chloroform (2 × 10 mL); the solvent
was evaporated to dryness to get the desired compound 6 (a–c) (data in
Table 1).
Method B
Compound 5 (0.217 g, 1 mmol) was heated under reflux either with
triethyl orthoacetate (6 mL) in acetic acid for 8 h or with trimethyl
orthoformate (6 mL) for 4–5 h. The solvent was removed in vaccu to
obtain the desired product as yellow powder (data in Table I).
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(2004).
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