Synthesis of 5-aryloxymethyl-2-bromo-5,6-dihydrothiazolo-[3,2-b]-1,2,4- triazoles

Full text of DOI:10.1134/S1070428013050321

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 5, pp. 782−783. © Pleiades Publishing, Ltd., 2013.
Original English Text © F.A. Khaliullin, E.E. Klen, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 5, pp. 797−798.
SHORT
COMMUNICATIONS
Synthesis of 5-Aryloxymethyl-2-bromo-5,6-dihydrothiazolo-
[3,2-b]-1,2,4-triazoles
F. A. Khaliullin and E. E. Klen
Bashkir State Medical University, Ufa, 450000 Russia
e-mail: khaliullin_ufa@yahoo.com
Received December 26, 2012
DOI: 10.1134/S1070428013050321
Derivatives of thiazolo[3,2-b]-1,2,4-triazole exhibit
versatile kinds of biological activity, in particular, anti-
phlogistic [1], antibacterial [2], anticonvulsant [3], anti-
cancer [4], and are promising objects for the search for
new biologically active substances. However the informa-
tion on the procedures of the synthesis of 5-substituted
5,6-dihydrothiazolo[3,2-b]-1,2,4-triazoles is limited
to the description of the preparation of 5-substituted
5,6-dihydrothiazolo[3,2-b]-1,2,4-triazol-6-ones and
5-arylidenethiazolo[3,2-b]-1,2,4-triazol-6-ones [3–5].
sium phenolates formed in situ in the reaction mixture
was carried out at boiling in ethanol or butanol. Similar
to the reaction with amines, thiirane (I) under the action
of the phenolates opened at the side of the less substituted
carbon atom in keeping with Krasusky rule [9] affording
5-aryloxymethyl-2-bromo-5,6-dihydrothiazolo[3,2-b]-
1,2,4-triazoles IIа–IId.
The composition and structure of obtained compounds
IIа–IId were confirmed by the elemental analysis, IR,
1Н and 13С NMR spectra.
We showed formerly that in the synthesis of
5-substituted 5,6-dihydrothiazolo[3,2-b]-1,2,4-triazoles
iit is possible to utilize the reactions of 3,5-dibromo-
1,2,4-triazole with monofunctional thiiranes [6] or with
3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole (I)
with amines [7, 8]. In extension of these studies we exam-
ined the reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-
1,2,4-triazole (I) with phenols.
The presence in the 1Н NMR spectra of compounds
IIb, IId in C6D6 of the characteristic signals of the
protons of NCH2 group in the form of two doublets
of doublets in the range 3.3–3.4 and 3.6–3.9 ppm and
of a multiplet of the proton of SСН group in the range
3.3–3.6 ppm confirms the formation of the fused sys-
tem of dihydrothiazolo[3,2-b]-1,2,4-triazole [7, 8]. In
1
the Н NMR spectra of compounds IIa, IIc in CDCl3
the proton signals of the dihydrothiazole ring are shifted
Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-
downfield by 1 ppm, therewith the signals of the protons
1,2,4-triazole (I) with 1.2–3-fold molar excess of potas-
N
N
N
N
OAr
ArOH
KOH
S
SH
Br
N
Br
Br
N
Br
I
N
N
S
Br
OAr
N
IIа_IId
Ar = C6H5 (а), C6H3Cl2-2,4 (b), C6H3Br2-2,4 (c), C6H2Cl3-2,4,6 (d).
782

SYNTHESIS OF 5-ARYLOXYMETHYL-2-BROMO-5,6-DIHYDROTHIAZOLO-[3,2-b]-1,2,4-TRIAZOLES
783
of the NCH2 group have a pattern of two АВ subspectra.
3J 8.7 Hz), 7.68 d (1Н, 3'-СНarom, 4J 2.3 Hz). 13С NMR
spectrum (CDCl3), δ, ppm: 49.01 (SCH), 49.49 (NCH2),
70.43 (5-CH2), 113.50 (C2 of phenol), 114.85 (C4 of
phenol), 115.15 (C6 of phenol), 131.56 (C5 of phenol),
135.93 (C3 of phenol), 142.91 (С2), 153.48 (C1 phenolа),
158.25 (С3а). Found, %: С 28.39; Н 1.92; N 8.74.
C11H8Br3N3OS. Calculated, %: С 28.11; Н 1.72; N 8.94.
The 13С NMR spectrum of dihydrothiazolotriazole
IIc contains the signals of carbon atoms at 49.01 (SCH)
and 49.49 (NCH2) ppm confirming the presence of the
dihydrothiazole ring [6]. The carbon atom signal from the
5-СН2 group appears at 70.43 ppm.
Thus the reaction of thiirane I with potassium
phenolates results in the formation of difficultly available
5-aryloxymethyl-2-bromo-5,6-dihydrothiazolo[3,2-b]-
1,2,4-triazoles.
2-Bromo-5-(2,4,6-trichlorophenoxy)methyl-5,6-
dihydrothiazolo[3,2-b]-1,2,4-triazole (IId) was obtained
using 2,4,6-trichlorophenol. Yield 0.33 g (80%), mp
1
87–89°С (EtOH–water), Rf 0.85. Н NMR spectrum
2-Bromo-5-phenoxymethyl-5,6-dihydrothiazolo-
[3,2-b]-1,2,4-triazole (IIа). To a solution of 0.13 g
(2.4 mmol) of KOH in 15 ml of ethanol was added 0.23 g
(2.4 mmol) of phenol, 0.60 g (2 mmol) of thiirane I, and
the mixture was boiled for 1.5 h. The solvent was distilled
off in a vacuum. The residue was washed with water and
triturated with ether. Yield 0.11 g (17%), mp 88–91°С
(C6D6), δ, ppm: 3.22–3.37 m (1Н, NCH2 and 2Н, 5-CH2),
3
3.50–3.62 m (1Н, SСН), 3.87 d.d (1Н, NСН2, J 4.1,
2J 11.0 Hz), 6.84 s (2Н, 3',5'-СНarom). Found, %: С 31.64;
Н 1.89; N 10.01. C11H7BrCl3N3OS. Calculated, %:
С 31.80; Н 1.70; N 10.11.
1Н and 13С NMR spectra were registered on a spec-
trometer BrukerAM-300 at operating frequencies 300 and
75 MHz respectively using as internal reference the residual
proton signals of the solvents [7.26 (CDCl3), 7.16 ppm
(C6D6)]. IR spectrum was recorded on a spectrophotom-
eter Infralyum FT-02. The individuality of compounds
obtained was checked by TLC on Silufol UV-254 plates
(eluent hexane–ethanol, 1 : 4). Thiirane I was obtained
by procedure [7].
1
(2-PrOH–water), Rf 0.76. Н NMR spectrum (CDCl3),
δ, ppm: 4.16–4.30 m (2Н, NСН2), 4.43–4.51 m (2Н,
5-СН2), 4.67–4.78 m (1Н, SСН), 6.90 d (2Н, 2',6'-СНarom
,
3J 7.8 Hz), 7.03 t (1Н, 4'-СНarom, 3J 7.4 Hz), 7.25–7.36 m
(2Н, 3',5'-СНarom). Found, %: С 42.13; Н 3.50; N 13.39.
C11H10BrN3OS., %: С 42.32; Н 3.23; N 13.46.
2-Bromo-5-(2,4-dichlorophenoxy)methyl-5,6-
dihydrothiazolo[3,2-b]-1,2,4-triazole (IIb). To a solution
of 0.17 g (3 mmol) of KОН in 15 ml of butanol was added
0.49 g (3 mmol) of 2,4-dichlorophenol, 0.30 g (1 mmol) of
thiirane I, and the mixture was boiled for 2 h. The solvent
was distilled off in a vacuum. Water was added to the resi-
due, the precipitate was filtered off and washed with water.
Yield 0.35 g (92%), mp 113–115°С (EtOH–water), Rf 0.78.
1Н NMR spectrum (C6D6), δ, ppm: 2.94 d (2Н, 5-СН2,
3J 6.9 Hz), 3.27 d.d (1Н, NСН2,3J 7.9, 2J 11.0 Hz), 3.56 d.d
(1Н, NСН2, 3J 3.3, 2J 11.0 Hz), 3.31–3.41 m (1Н, SСН),
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4
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Compounds IIc, IId were similarly obtained.
2-Bromo-5-(2,4-dibromophenoxy)methyl-5,6-
dihydro-thiazolo[3,2-b]-1,2,4-triazole (IIc) was ob-
tained using 2,4-dibromophenol. Yield 0.38 g (81%),
mp 118–120°С (EtOH–water), Rf 0.61. IR spectrum (KBr),
ν, cm–1: 3080.5, 2929.2, 2866.3 (С–Н); 1480.8, 1433.1,
1
1287.8, 1250.6, 1218.8 (С–N, С=N, С=С). Н NMR
spectrum (CDCl3), δ, ppm: 4.14–4.33 m (2Н, NСН2),
4.43–4.62 m (2Н, 5-СН2), 4.69–4.82 m (1Н, SСН), 6.79 d
(1Н, 6'-СНarom,3J 8.7 Hz), 7.38 d.d (1Н, 5'-СНarom,4J 2.3,
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