Thiophene-2-carbaldehyde and benzaldehyde thiosemicarbazones in reactions with propargyl bromide and 1,3-dibromopropyne

Article abstract of DOI:10.1134/S1070428009020122

The reaction of thiophene-2-carbaldehyde and benzaldehyde thiosemicarbazones with propargylbromide in methanol provided S-(2-propyne)thiosemicarbazones hydrobromides of thiophene-2-carbaldehyde and benzaldehyde. Reaction products obtained from thiosemicar

Full text of DOI:10.1134/S1070428009020122

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 2, pp. 226−228. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.N. Elokhina, A.S. Nakhmanovich, L.I. Larina, T.I. Yaroshenko, S.V. Amosova, 2009, published in Zhurnal Organicheskoi
Khimii, 2009, Vol. 45, No. 2, pp. 238−240.
Thiophene -2-carbaldehyde and Benzaldehyde Thiosemicarbazones
in Reactions with Propargyl Bromide and 1,3-Dibromopropyne
V. N. Elokhina,A. S. Nakhmanovich, L. I. Larina, T. I. Yaroshenko, and S. V.Amosova
Faworsky Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences
Irkutsk, 664033 Russia
e-mail: yaroshenko@irioch.irk.ru
Received April 3, 2008
Abstract—The reaction of thiophene-2-carbaldehyde and benzaldehyde thiosemicarbazones with propargyl-
bromide in methanol provided S-(2-propyne)thiosemicarbazones hydrobromides of thiophene-2-carbaldehyde
and benzaldehyde. Reaction products obtained from thiosemicarbazones and 1,3-dibromopropyne in methanol at
heating were 2-thenilydene(benzylidene)azino-4-bromomethylidene-4,5-dihydrothiazol-3-ium bromides.
DOI: 10.1134/S1070428009020122
Thiosemicarbazones of aromatic and heterocyclic
aldehydes and ketones are efficient ligands for complexing
[1–3] and exhibit a high biological activity. Among these
compounds substances were found possessing tuberculo-
cidal [4–6], antimicrobial [7, 8], antibacterial [9], antiviral
[10], antitumor [11], and malaricidal [12] actions.
carboxylate or dimethyl acetylenedicarboxylate in
methanol at heating were substituted 1,3-thiadiazolidin-
4-ones.
In this study we investigated the reaction of thiophene-
2-carbaldehyde and benzaldehyde thiosemicarbazones (I
and II) with propargyl bromide (III) and 1,3-dibromo-
propyne (IV) in anhydrous methanol at heating. In the
reaction with propargyl bromide the only reaction products
were S-(2-propyne)thiosemicarbazone hydrobromides of
thiophene-2-carbaldehyde (V) and benzaldehyde (VI).
In the IR spectra of the compounds appeared the absorp-
tion bands of the acetylene bond at 2120 and 2125 cm–1.
In the 1H NMR spectra the proton signals of the fragment
C≡CH were observed as singlets at 3.46 and 3.51 ppm.
Reactions of thiosemicarbazones with acetylene
compounds up till now remain poorly understood. We
described formerly a synthesis of substituted 1,3-thiazin-
4-ones by a reaction of methyl propiolate with thiosemi-
carbazones in ΜeOH in the presence of triethylamine
[13]. By the reaction of thiosemicarbazones with terminal
α-acetylene ketones in MeCN at 20°C substituted 1,3,4-
thiadiazolines were obtained in 83–97% yields [14].
It was reported in [15] that the reaction products
obtained from thiosemicarbazones and acetylenedi-
Quite differently proceeded the reaction of thiosemi-
carbazones of thiophene-2-carbaldehyde (I) and
HC CCH2Br
R
CH N NH
III
SCH2C
HBr
CH
.
HN
R
CH N NH
V, VI
S
BrC CCH2Br
.
H2N
R
HC N
NH
HBr
R
HC N
NH
IV
I, II
S
S
_
Br
+
HN
:
H2N
CBr
CHBr
A
VII, VIII
R = 2-thienyl (I, V, VII), Ph (II, VI, VIII).
226

THIOPHENE -2-CARBALDEHYDE AND BENZALDEHYDE THIOSEMICARBAZONES
227
benzaldehyde (II) with 1,3-dibromopropyne (IV) in
anhydrous methanol at heating. Presumably intermediately
S-(1-bromo-2-propyne)thiosemicarbazone hydrobromides
formed of thiophene-2-carbaldehyde and benzaldehyde
that under the synthesis conditions underwent the
intramolecular cyclization into 2-thenilydeneazino-4-
bromomethylidene-4,5-dihydrothiazol-3-ium bromide
(VII) and 2-benzylideneazino-4-bromomethylidene-4,5-
dihydrothiazol-3-ium bromide (VIII).
S-(2-Propyne)thiosemicarbazone hydrobromide
of thiophene-2-carbaldehyde (V). To a solution of
0.93 g (5 mmol) of thiophene-2-carbaldehyde thiosemi-
carbazone (I) in 20 ml of anhydrous methanol was added
at stirring a solution of 0.6 g (5 mmol) of propargyl bromide
(III) in 15 ml of anhydrous methanol. The reaction mixture
was brought to boiling, it was stirred for 2 h, the solvent
was partially evaporated, the solution was cooled to 0°C,
the precipitated crystals were filtered off, washed on the
filter with cold methanol, and dried in a vacuum. Yield
1.03 g (67%), colorless crystals, mp 189–191°C. IR
spectrum, ν, cm–1: 590 (C–S), 1420 (CH2, bend.), 1580,
1635 (C=N, C=C), 2120 (C≡C), 2940 (CH2), 3220 (NH2).
1H NMR spectrum, δ, ppm: 3.46 s (1H, a”CH), 4.27 s
(2H, CH2), 7.18–7.70 m (3H, C4H3S), 8.61 s (1H,
CH=N), 9.65 s (2H, NH2). 13C NMR spectrum, δ, ppm:
20.32 (CH2), 76.10 (≡CH), 77.93 (CH2C≡), 128.39,
132.23, 134.47, 136.59 (Carom), 148.11 (CH=N), 161.71
(N=CS). 15N NMR spectrum, δ, ppm: –76.2 (CH=N),
–206.2 (NH). Found, %: C 35.15; H 3.19; Br 26.39;
N 13.55; S 20.74. C9H10BrN3S2. Calculated, %: C 35.53;
H 3.29; Br 26.32; N 13.82; S 21.05.
S-(2-Propyne)thiosemicarbazone hydrobromide
of benzaldehyde (VI) was obtained similarly to
compound V from 0.6 g (5 mmol) of benzaldehyde
thiosemicarbazone (II) and 0.6 g (5 mmol) of propargyl
bromide (III) in anhydrous methanol at 65°C. Yield
1.22 g (82%), colorless crystals, mp 206–208°C. IR
spectrum, ν, cm–1: 585 (CS), 1420 (CH2, bend.), 1585,
1640 (C=N, C=C), 2125 (C≡C), 2945 (CH2), 3245 (NH2).
1H NMR spectrum, δ, ppm: 3.51 s (1H, ≡CH), 4.39 s
(2H, CH2), 7.47–7.96 m (5H, C6H5), 8.50 s (1H, CH=N),
9.98 br.s (2H, NH2). 13C NMR spectrum, δ, ppm: 20.44
(CH2), 76.09 (≡CH), 77.70 (CH2C≡), 128.54, 128.80,
131.78, 132.37 (Carom), 152.99 (CH=N), 162.58 (N=CS).
15N NMR spectrum, δ, ppm: –70.2 (CH=N), –207.3
(NH). Found, %: C 44.12; H 3.89; Br 26.76; N 14.24;
S 11.07. C11H12BrN3S. Calculated, %: C 44.30, H 4.03;
Br 26.85; N 14.09; S 10.74.
The composition and structure of synthesized
compounds V–VIII were proved by elemental analysis
and IR and 1H,13C, 15N NMR spectra. The IR spectra of
compounds VII and VIII lack the absorption bands of
the acetylene bond. In the 1H NMR spectra the signals
of the protons from the fragment =CHBr give rise to
singlets at 6.53 and 6.69 ppm, the signals from the NH
group of the ring and HN appear as broad singlets at
10.08 and 11.00 ppm. In the 13C NMR spectra of
compounds VII and VIII the carbon atoms of the group
=CHBr are observed at 87.68 and 90.06 ppm.
In 2D 1H–15N HMBC spectra of compounds V–VIII
only two nitrogen signals are observed: of imine nitrogen
atom (CH=N) in the region – 70–82 ppm and amine
nitrogen atom (–NH–) in the region –204–207 ppm. The
imine atom N1 gives a cross-peak with the proton CH=N,
whereas the amine nitrogen atom gives cross-peaks with
the protons of fragments CH2, =CHBr, and CH=N.
Therefore it is presumable that the atoms N2 and N3 are
structurally equivalent, and the structure of the
compounds may be depicted as follows:
1
2
NH.
R
CH N
2
NH.
1
.
.
.
HBr
SCH2C
R
CH N
.
+
S
.
.
Br_
.
.
.
CH
.
HN
.
3
HN
3
CHBr
VII, VIII
V, VI
The reaction carried out in dioxane at microwave
activation (4 min, power 360 W) gave the product in 55%
yield, mp 208°C. The microwave activation significantly
reduced the reaction time, but the yield was smaller due
to the tarring of the reaction mixture.
2-Thenylideneazino-4-bromomethylidene-4,5-
dihydrothiazol-3-ium bromide (VII). To a solution of
0.93 g (5 mmol)of thiophene-2-carbaldehyde thiosemi-
carbazone (I) in 15 ml of anhydrous methanol added at
stirring 0.99 g (5 mmol) of 1,3-dibromopropyne (IV) in
15 ml of anhydrous methanol. The reaction mixture was
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Specord 75IR from KBr pellets. 1H, 13C, and 15N NMR
spectra were registered from solutions of compounds in
DMSO-d6 at 20OC on a spectrometer Bruker DPX-400
(at operating frequencies 400.13, 100.62, and 40.54 MHz
respectively). As internal reference for 1H and 13C NMR
spectra was used HMDS, for 15N NMR spectra,
MeNO2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

ELOKHINA et al.
228
brought to boiling, it was stirred for 2.5 h, methanol was
partly evaporated, the solution was cooled to 0°C, the
precipitated crystals were filtered off, washed on the filter
with cold methanol, and dried in a vacuum. Yield 1.74 g
(91%), colorless crystals, mp 162–164°C. IR spectrum,
ν, cm–1: 585 (CS), 1430 (CH2, bend.), 1590, 1630 (C=N,
C=C), 2930 (CH2), 3440 (NH, HN+). 1H NMR spectrum,
δ, ppm: 4.38 s (2H, CH2), 6.53 s (1H, =CHBr), 7.29–
8.04 m (3H, C4H3S), 8.86 s (1H, CH=N), 10.00 br.s (1H,
NH), 10.80 br.s (1H, NH in the ring). 13C NMR spectrum,
δ, ppm: 34.62 (CH2), 87.68 (=CHBr), 128.58, 134.37,
135.25, 136.72 (Carom), 136.46 (C=CHBr), 162.04
(CH=N), 169.11 (N=CS). 15N NMR spectrum, δ, ppm:
–82.8 (CH=N), –204.0 (NH). Found, %: C 28.54; H 2.12;
Br 42.05; N 10.71; S 16.54. C9H9Br2N3S2. Calculated,
%: C 28.20; H 2.35; Br 41.78; N 10.97; S 16.71.
The reaction carried out in dioxane at microwave
activation in 4 min gave the product in 48% yield.
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2-Benzylideneazino-4-bromomethylidene-4,5-
dihydrothiazol-3-ium bromide (VIII) was obtained
similarly to compound VII from 3 g (5 mmol) of benz-
aldehyde thiosemicarbazone (II) and 0.99 g (5 mmol) of
1,3-dibromopropyne in anhydrous methanol at heating.
Yield 1.45 g (77%), colorless crystals, mp 189–190°C.
IR spectrum, ν, cm–1: 580 (CS), 1435 (CH2, bend.), 1585,
1
1640 (C=N, C=C), 2935 (CH2), 3150 (NH). H NMR
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spectrum, δ, ppm: 4.02 s (2H, CH2), 6.69 s (1H, =CHBr),
7.52–8.03 m (5H, C6H5), 8.53 s (1H, CH=N), 10.20 br.s
(1H, HN), 11.00 br.s (1H, NH in the ring). 13C NMR
spectrum, δ, ppm: 35.20 (CH2), 90.06 (=CHBr), 129.09,
129.38, 131.69, 132.82 (Carom), 135.94 (C=CHBr), 164.39
(CH=N), 169.99 (N=CS). 15N NMR spectrum, δ, ppm:
–78.3 (CH=N), –204.6 (NH). Found, %: C 35.40; H 2.98;
Br 42.34; N 10.98; S 8.30. C11H11Br2N3S. Calculated,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009