Thiobenzohydrazides and dithiocarbazates in the synthesis of new 1,3,4-thiadiazine and 1,3,4-thiadiazole derivatives

Full text of DOI:10.1134/S1070363209070263

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 7, pp. 1583–1584. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © N.N. Kuz’mich, B.Yu. Lalaev, I.P. Yakovlev, T.L. Semakova, V.E. Zakhs, 2009, published in Zhurnal Obshchei Khimii, 2009,
Vol. 79, No. 7, pp. 1226–1227.
LETTERS
TO THE EDITOR
Thiobenzohydrazides and Dithiocarbazates in the Synthesis
of New 1,3,4-Thiadiazine and 1,3,4-Thiadiazole Derivatives
N. N. Kuz’mich, B. Yu. Lalaev, I. P. Yakovlev, T. L. Semakova, and V. E. Zakhs
St. Petersburg State Chemical and Pharmaceutical Academy, ul. Professora Popova 14, St. Petersburg, 197376 Russia
e-mail: nnkuzmich@mail.ru
Received April 24, 2009
DOI: 10.1134/S1070363209070263
We previously reported on reactions of aromatic
and heteroaromatic acid hydrazides with oxalyl
chloride in boiling benzene, which afforded 80–90% of
the corresponding 2-aryl(hetaryl)-4H-1,3,4-oxadiazine-
5,6-diones [1]. Analogous 4H-1,3,4-thiadiazine-5,6-
diones IIIa–IIIf were synthesized by reaction of
carbothiohydrazides Ia–Ie and S-methyl-3-phenyldi-
thiocarbazate (If) with 10–15% excess of oxalyl
chloride (II) in anhydrous inert solvents (benzene,
chloroform, carbon tetrachloride). The yields of
thiadiazines IIIa–IIIf were 80–94%.
tion pattern with formation of 1,3,4-thiadiazine ring,
whereas the reaction in fairly polar coordinating
medium (THF) at different temperatures occurs as
[4+1]-condensation with formation of five-membered
1,3,4-thiadiazole derivatives.
The structure of compounds IIIa–IIIf and IV was
1
confirmed by H and 13C NMR, IR, UV, and mass
spectra.
2-Phenyl-4H-1,3,4-thiadiazine-5,6-dione (IIIa). A
solution of 2.92 g of oxalyl chloride (II) in 50 ml of
anhydrous chloroform was cooled to 0°C, 3.04 g of
thiobenzohydrazide (Ia) was added under stirring, and
the mixture was heated for 3 h under reflux. The
mixture was cooled, and the precipitate was filtered off
and recrystallized twice from acetonitrile. Yield 3.38 g
However, the reaction of thiobenzohydrazide (Ia)
with oxalyl chloride (II) in tetrahydrofuran in the
temperature range from 15–65°C gave 72% of 5,5'-
diphenyl-2,2'-bi-1,3,4-thiadiazole (IV). The reaction
temperature strongly affected the reaction rate. The
reaction in boiling THF was complete in 2 h, and it
took 8 h at 15°C. Thus thiobenzohydrazides Ia–Ie and
S-methyl-3-phenyldithiocarbazate (If) react with
oxalyl chloride in weakly polar solvents (benzene,
chloroform, etc.), following the [4+2]-cyclo-condensa-
(82%), mp 225–227°C (decomp.). UV spectrum, λmax
,
nm: 207, 233, 270. IR spectrum, ν, cm–1: 3190, 1695,
1
1675, 1450. H NMR spectrum (DMSO-d6), δ, ppm:
7.51–7.68 m (5H), 12.90 s (1H). 13C NMR spectrum
(DMSO-d6): δC, ppm: 125.8, 129.2, 130.9, 133.7, 141.6,
148.6, 176.4. Mass spectrum: m/z 206 [M]+.
R2
R2
CHCl3, CCl4 or
C6H6, 60−80oC
NH
S
N
O
Cl
Cl
O
O
HN
N
+
R1
R1
S
O
Iа−If
II
IIIа−IIIf
S
Cl
Cl
O
O
N
N
S
THF, 15−65oC
Ph
NH
NH2
N
N
+
S
Ph
Ph
Iа
II
IV
R1 = Ph (а, c, e), 4-FC6H4 (b, d), CH3S (е); R2 = H (а, b), Ph (c, d, f) PhCH2 (e).
1583

1584
KUZ’MICH et al.
2-(4-Fluorophenyl)-4H-1,3,4-thiadiazine-5,6-dione
(IIIb) was synthesized in a similar way. Yield 4.13 g
anhydrous carbon tetrachloride was cooled to 0°C, a
solution of 5.88 g of oxalyl chloride (II) in 15 ml of
the same solvent was added under stirring, and the
mixture was heated for 4 h under reflux, cooled, and
evaporated to dryness under reduced pressure. The
residue was treated with ~30 ml of n-heptane–carbon
tetrachloride (3:1), the mixture was heated to the
boiling point and kept boiling for 3 min, and the
yellow solution was separated by decanting from the
undissolved material. This procedure was repeated 3–4
times. The extracts were combined and cooled to 0°C,
and the precipitate was filtered off, washed with cold
hexane, and dried. Yield 1.79 g (87%), mp 80–82°C.
UV spectrum, λmax, nm: 208.0, 247.0, 281.0. IR
(92%), mp 232–234°C (decomp.). UV spectrum, λmax
,
nm: 207, 233, 270. IR spectrum, ν, cm–1: 3120, 1685,
1
1655, 1595. H NMR spectrum (DMSO-d6), δ, ppm:
7.51 t (2H), 7.71 d.d (2H), 12.96 s (1H). 13C NMR
spectrum (DMSO-d6), δC, ppm: 114.5, 114.9, 129.5,
129.7, 135.1, 143.2, 148.7, 160.8, 170.4, 176.5. Mass
spectrum: m/z 224 [M]+.
2,4-Diphenyl-4H-1,3,4-thiadiazine-5,6-dione (IIIc).
A solution of 2.79 g of oxalyl chloride (II) in 5 ml of
anhydrous benzene was added under stirring to a
solution of 4.56 g of thiohydrazide Ic in 30 ml of
anhydrous benzene. The mixture was heated for 4 h
under reflux and cooled, and the mixture was filtered
off and recrystallized from benzene–acetonitrile (2:1).
Yield 5.25 g (93%), mp 212–214°C. UV spectrum,
λmax, nm: 208.0, 242.5, 337.5. IR spectrum, ν, cm–1:
1
spectrum, ν, cm–1: 3060, 2930, 1695, 1670, 1550. H
NMR spectrum (DMSO-d6), δ, ppm: 2.51 s (3H),
7.39–7.54 m (5H). 13C NMR spectrum (CDCl3), δC,
ppm: 15.19, 125.5, 128.2, 128.9, 140.6, 141.7, 148.0,
175.6. Mass spectrum: m/z 252 [M]+.
1
3150, 1680, 1660, 1610. H NMR spectrum (DMSO-
d6): δ 7.34–7.72 ppm, m (10H). 13C NMR spectrum
(DMSO-d6), δC, ppm: 125.1, 126.0, 128.0, 128.3,
128.8, 131.2, 133.3, 140.9, 141.1, 147.8, 175.4. Mass
spectrum: m/z 282 [M]+.
5,5′-Diphenyl-2,2′-bi-1,3,4-thiadiazole (IV). A
solution of 2.02 g of thiobenzohydrazide (Ia) in 11.0
ml of anhydrous THF was cooled to 0°C, a solution of
1.85 g of oxalyl chloride in 5.5 ml of the same solvent
was added, and the mixture was heated for 2 h under
reflux. The precipitate was filtered off and washed
with cold methylene chloride, and the filtrate was
concentrated under reduced pressure to isolate an
additional amount of the product. Recrystallization
from dimethylformamide gave pure compound IV as
fine needles. Yield 1.54 g (72%), mp 256–258°C. UV
spectrum, λmax, nm: 205.0, 231.5, 337.0. IR spectrum,
2-(4-Fluorophenyl)-4-phenyl-4H-1,3,4-thiadiazine-
5,6-dione (IIId) was synthesized in a similar way.
Yield 5.11 g (85%), mp 181–183°C. UV spectrum,
λmax, nm: 208.0, 243.0, 334.0. IR spectrum, ν, cm–1:
1
3065, 1695, 1665, 1595, 1510. H NMR spectrum
(DMSO-d6), δ, ppm: 7.35 t (2H), 7.41–7.60 m (5H),
7.77 d.d (2H). 13C NMR spectrum (DMSO-d6), δC,
ppm: 115.4, 116.6, 123.8, 126.4, 129.2, 132.3, 135.3,
140.2, 148.7, 160.8, 170.2, 177.3. Mass spectrum: m/z
300 [M]+.
1
ν, cm–1: 3065, 1620, 1455, 1415. H NMR spectrum
(CF3COOD): δ 7.47–7.89 ppm, m (10H). 13C NMR
spectrum (CF3COOD), δC, ppm: 126.3, 131.2, 132.7,
138.3, 160.1, 180.0. Mass spectrum: m/z 322 [M]+.
4-Benzyl-2-phenyl-4H-1,3,4-thiadiazine-5,6-dione
(IIIe). A solution of 2.79 g of oxalyl chloride (II) in
5 ml of anhydrous benzene was added under stirring to
a suspension of 4.84 g of thiohydrazide Ie in 30 ml of
anhydrous benzene. The mixture was heated for 3.5 h
under reflux and cooled, the solvent was removed
under reduced pressure, and the precipitate was filtered
off and recrystallized twice from benzene–hexane
(2:3). Yield 5.57 g (85%), mp 134–136°C. UV
spectrum, λmax, nm: 206.5, 244.0, 285.0. IR spectrum,
1
13
The H and C NMR spectra were recorded from
solutions in DMSO-d6, CDCl3, or CF3COOD on
Bruker WM-400 (1H, 400 MHz) and Bruker AC-200
spectrometers (13C, 50 MHz) using hexamethyldi-
siloxane as internal reference. The UV spectra were
measured from solutions in 96% ethanol on an SF-
2000 spectrophotometer. The IR spectra were recorded
in KBr on an FSM-1201 spectrometer with Fourier
transform. The mass spectra (electron impact, 70 eV)
were obtained on an MKh-1321 instrument (direct
sample admission into the ion source heated to 200°C).
1
ν, cm–1: 3065, 2960, 1690, 1660, 1490. H NMR
spectrum (CDCl3), δ, ppm: 5.23 s (2H), 7.30–7.65 m
(10H). 13C NMR spectrum (CDCl3), δC, ppm: 56.6,
126.2, 128.4, 128.7, 129.1, 129.2, 131.4, 133.6, 135.2,
141.5, 148.1, 175.0. Mass spectrum: m/z 296 [M]+.
REFERENCE
2-Methylsulfanyl-4-phenyl-4H-1,3,4-thiadiazine-
5,6-dione (IIIf). A suspension of 8.34 g of methyl 2-
phenylhydrazinecarbodithioate (If) in 75 ml of
1. Kuz’mich, N.N., Lalaev, B.Yu., Yakovlev, I.P., Peti-
na, O.A., Strelkova, L.F., and Zakhs, V.E., Russ. J. Gen.
Chem., 2007, vol. 77, no. 6, p. 1100.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 7 2009