Sodium Hydroxide: A Mild and Inexpensive Catalyst for the Regioselective Synthesis of 2-Substituted 5-Methylthiazolo[3,2-A]-s-triazoles

Article abstract of DOI:10.1039/a802038h

The facile and regioselective synthesis of 2-substituted 5-methylthiazolo[3,2-b]-s-triazoles has been performed by the catalytic action of NaOH on 3-propynylthio-s-triazoles.

Full text of DOI:10.1039/a802038h

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488 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 488±489$
Sodium Hydroxide: a Mild and Inexpensive Catalyst
for the Regioselective Synthesis of 2-Substituted
5-Methylthiazolo[3,2-b]-s-triazoles$%
Majid. M. Heravi*a and Mahmood Tajbakhshb
aChemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Iran
bDepartment of Chemistry, University of Mazandaran, Iran
The facile and regioselective synthesis of 2-substituted 5-methylthiazolo[3,2-b]-s-triazoles has been performed by the
catalytic action of NaOH on 3-propynylthio-s-triazoles.
Thiazolo[3,2-b]-s-triazoles 3 were ®rst synthesized by Potts
Table 1 Synthesis of prop-3-ynylthio-s-triazoles (2a±g)
and Hussain1 via the reaction of 1 with chloroacetone and
Yield
(%)
Recrystallisation
solvent
subsequent dehydration of the corresponding ketone in the
presence of POCl3. In 1978, Srinvasan and co-workers2
reported the synthesis of 5-arylprop-3-ynlthio-s-triazoles 2 in
moderate yields, through the reaction of 1 with propynyl
bromide, in the presence of sodium acetate. Further annula-
tion of 2 to give thiazolo [3,2-b]-s-triazoles has been also
reported under mercury(II) acetate catalysis in poor to
moderate yields.2
Product
R
Mpa/8C
2a
2b
2c
2d
2e
2f
H
Me
Ph
o-MeC6H4
p-MeC6H4
o-ClC6H4
p-ClC6H4
68
59
72
71
68
75
67
109
126
ethanol
ethanol
benzene
benzene
benzene
benzene
benzene
127 (128)
144 (145)
92 (90)
85 (84)
144 (145)
2g
a1st values, 2nd in parentheses.
with subsequent neutralization a single (TLC) compound
was obtained. Its 1H NMR showed signals at d 2.5 (d,
J ˆ 1.5 Hz 3 H, Me), 2.6 (s, 3 H, Me), 6.5 (q, J ˆ 1.5 Hz,
CH of thiazole).
Although fusion of thiazole and the triazole nuclei
can occur in two di€erent ways to give thiazolo[3,2-b]-s-
triazole 3 and thiazolo[2,3-c]-s-triazole 4, from analytical,
spectral and melting point data as well as by comparison
with an authentic sample, the product was identi®ed as
2,5-dimethylthiazolo[3,2-b]-s-triazole 3 (R ˆ Me). This indi-
cates that sodium hydroxide has smoothly catalyzed regio-
selective cyclization and isomerization of the acetylenic
moiety of the propynylthio group. The reaction proceeds via
5-exo-diagonal cyclization3 followed by isomerization and
aromatization4±6 A mechanism is suggested in Scheme 1.
Various prop-3-ynylthio-s-triazoles 2 were employed in
order to prepare condensed thiazoles and to establish the
generality of method. We found that one-pot cyclization
and aromatization of 2 to 3 can be carried out in high
regioselectivity and excellent yields. Melting points are
reported in Table 2.
In conclusion in comparison with the presently available
synthetic methods1,2 which show drawback's from the stand
point of yields, price and limited availability of catalyst or
low regioselectivity, the eciency of the present method
is apparent from the availability of inexpensive sodium
hydroxide and the unique regioselectivity as well as high
yield with lack of side products. Owing to the simplicity of
the conditions and use of inexpensive catalyst this method-
ology should ®nd utility in organic synthesis.
In the above attempt to prepare 22, through use of 1,
propynyl bromide and alkali, the moderate yields obtained
perhaps is due to formation of 3-allenylthio substituted
s-triazole derivatives via the intermediacy of an s-propynyl
derivative 2.
Here, we report
a simple and ecient synthesis of
3-propynylthio-s-triazoles 2 and regioselective cyclization of
the latter to give 3 in moderate to high yields.
When compound
1
(R ˆ Me) was condensed with
propynyl bromide in re¯uxing absolute ethanol in the
absence of base, prop-3-ynylthio-s-triazole 2 (R ˆ Me) was
obtained, mp ˆ 126 8C. In the 1H NMR spectrum of this
compound methylene protons appear as a doublet and
the acetylenic proton as triplet showing a long range
coupling (J ˆ 2.4 Hz). To establish the generality of method,
several 5-substituted 3-thio-s-triazoles 1 were employed and
condensed with propynyl bromide to a€ord 2 in good to
excellent yields (Table 1).
For cyclization of
2
(R ˆ Ph) in moderate yield,
Srinvasan and co-workers used mercury(II) acetate which
is poisonous and expensive. However the use of 1 M
sodium hydroxide solution for cyclization obviated these
disadvantages and regioselective cyclization occurred to give
the desired products in much better yield. Thus when 2
(R ˆ Me) was re¯uxed in 1 M sodium hydroxide solution
Experimental
Melting points (uncorrected) were obtained on a Ko‚er Hazbank
Rischart type 4841 apparatus. The 1H NMR spectra were obtained
on a Varian 60A spectrometer and mass spectra were scanned on a
Varian Mat CH-7 instrument at 70 eV.
Preparation of 5-Substituted 3-Propynylthio-s-triazoles (2) (Typical
Procedure).ÐAn appropriate 3-thioxo-s-triazole (5 mmol) was dis-
solved in ethanol (50 ml) to which was added propynyl bromide
(5 mmol) dropwise. This mixture was re¯uxed for 3 h. After evapor-
ation of solvent and pouring the residue into crushed ice, the solid
that separated was ®ltered and crystallized from a suitable solvent
(see Table 1).
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
%This paper is dedicated to Professor A. Sha®ee on the occasion of
his 60th birthday.

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J. CHEM. RESEARCH (S), 1998 489
Table 2 Synthesis of 2-substituted 5-methylthiazolo[3,2-b]-s-triazoles (3a±g)
Product
R
Yield (%)
Mp/8C
Recrystallisation solvent
3a
3b
3c
3d
3e
3f
H
Me
Ph
o-MeC6H4
p-MeC6H4
o-ClC6H4
p-ClC6H4
95
92
90
85
80
90
80
66±70
ethanol
ethanol
69±70 (lit.,1 68±69)
124±125 (lit.,1 123)
84±85 (lit.,2 85)
142 (lit.,2 141)
84±85 (lit.,2 82)
117±118 (lit.,2 118)
chloroform
chloroform
methanol
chloroform
chloroform
3g
Selected Data for 2a.ÐꢀH ([2H6]DMSO) 3.05 (t, J ˆ 2.4 Hz, 1 H,
2CH), 3.9 (d, J ˆ 2.4 Hz, 2 H, CH2), 8.45 (s, 1 H, CH of triazole).
IR (KBr disc), v 3240, 2850, 2500, 2110 cm 1; m/z (%) 139(4),
138(6), 137(48), 110(76), 84(51), 38(80), 32(67), 28(100).
Selected Data for 3b.ÐꢀH (CDCl3) 2.5 (d, J ˆ 1.5 Hz, 3 H, CH3),
2.6 (s, 3 H, CH3), 6.55 (q, J ˆ 1.5 Hz, 1 H, CH of thiazole ring). IR
(KBr disc), v 3070, 3020, 3000, 1580, 1500 cm 1; m/z (%) 153 (5),
152 (10), 151 (100), 110 (32), 70 (23), 66 (56), 44 (23), 28 (23).
Selected Data for 3c.ÐꢀH(CDCl3) 2.55 (d, J ˆ 1.5 Hz, 3 H, CH3),
6.55 (q, J ˆ 1.5 Hz, 1 H, CH of thiazole ring), 7.3±7.6 (m, 3 H of
Ph), 8.83 (m, 2 H of Ph). IR (KBr disc), v 3100, 1475, 1450, 1320,
1280, 710 cm 1; m/z (%) 215 (4), 212 (100), 142 (35), 101 (46), 70
(95), 32 (54).
Selected Data for 2b.ÐꢀH ([2H6]DMSO) 2.5 (t, J ˆ 2.4 Hz, 1 H,
2CH), 2.7 (s, 3 H, CH3), 4.0 (d, J ˆ 2.4 Hz, 2 H, CH2). IR (KBr
disc), v 3230, 2500, 2850, 2100 cm 1; m/z (%) 153 (4), 159(20), 150
(79), 149 (65), 110 (70), 84 (54), 28 (100).
Selected Data for 2c.ÐꢀH (CDCl3), 2.35 (t, J ˆ 2.4 Hz, 1 H,
2CH), 4.0 (d, J ˆ 2.4 Hz, 2 H, CH2), 7.45±7.70 (m, 5 H, Ph). IR
(KBr disc), v 3300, 2500, 2850 cm 1; m/z (%) 215 (10), 213 (3), 212
(18), 211 (18), 102 (19), 32 (27), 28 (100).
Received, 13th March 1998; Accepted, 11th May 1998
Paper E/8/02038H
Preparation of 2-Substituted 5-Methylthiazolo[3,2-b]-s-triazoles (3)
(Typical Procedure).ÐAn appropriate prop-3-ynylthio compound 2
(0.01 mol) was dissolved in 1 M NaOH (20 ml) and the mixture
re¯uxed for 2 h. The reaction mixture was cooled to room tempera-
ture and neutralized by addition of HCl. The solid was ®ltered o€
and crystallized from suitable solvent (see Table 2).
Selected Data for 3a.ÐꢀH (CDCl3), 2.6 (d, J ˆ 1.5 Hz, 3 H,
CH3), 6.7 (q, J ˆ 1.5 Hz, 1 H, CH of thiazole ring), 8.25 (s, 1 H,
CH of triazole ring). IR (KBr disc), v 3050, 1480, 1400, 1180,
650 cm 1; m/z (%) 139 (2), 138 (13), 136 (100), 110 (70), 66 (67), 32
(39), 27 (25), 28 (98), 16 (30).
References
1 K. T. Potts and S. Hussain, J. Org. Chem., 1971, 36, 10.
2 Pramod Upadhyaya, T. G. Surendra Nath and V. R. Srinvasan,
Synthesis, 1978, 288.
3 J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976, 434.
4 M. M. Heravi and M. Bakavoli, J. Chem. Res. (S), 1995, 11, 480.
5 M. M. Heravi, M. Shafaie, M. Bakavoli, M. M. Sadeghi and
A. R. Khoshdast, Indian J. Chem., Sect. B, 1996, 35, 1260; Chem.
Abstr., 1996, 126, 1442,44a.
6 M. M. Heravi, K. Aghapoor, M. A. Nooshabadi and M. M.
Mojtahedi, Monatsh. Chem., 1997, 128, 1143.