Three-component and one-pot reaction between phenacyl bromide and primary amines in the presence of carbon disulfide

Article abstract of DOI:10.3184/174751912X13568926198645

A three-component and one-pot reaction between phenacyl bromide and primary amines in the presence of carbon disulfide to afford substituted 4-hydroxy-4-phenylthiazolidine-2-thiones in high yields.

Full text of DOI:10.3184/174751912X13568926198645

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 71
FEBRUARY, 71–72
Three-component and one-pot reaction between phenacyl bromide and
primary amines in the presence of carbon disulfide
Alireza Hassanabadi* and Khatereh Khandan-Barani
Department of Chemistry, Islamic Azad University, Zahedan Branch, PO Box 98135-978, Zahedan, Iran
A three-component and one-pot reaction between phenacyl bromide and primary amines in the presence of carbon
disulfide to afford substituted 4-hydroxy-4-phenylthiazolidine-2-thiones in high yields.
Keywords: thiazolidine-2-thiones, phenacyl bromide, carbon disulfide, primary amines
Multi-component reactions (MCRs) have been frequently used
by synthetic chemists as a means to generate molecular diver-
sity from bifunctional substrates that react sequentially in an
intramolecular fashion.1–4 Dithiocarbamates have received
considerable attention due to their numerous biological activi-
ties.5–8 their pivotal role in agriculture,9–11 and as linkers in
solid-phase organic synthesis.12–14 Dithiocarbamates are also
widely used in medicinal chemistry and have found applica-
tion in the treatment of cancer.15,16 Therefore, synthesis of these
compounds has received considerable attention. General
methods for their synthesis involve the reaction of an amine
with costly and toxic reagents, such as thiophosgene or isothio-
cyanate.17 As a part of our current studies on the development
of new routes in organic synthesis,18–21 we report here an effi-
cient one-pot synthesis of thiazolidine-2-thiones employing
readily available starting materials.
For example, the 1H NMR spectrum of 3a exhibited a single
line was observed at δ = 5.22 which arises from the OH proton
and disappeared by addition of D2O to the CDCl3 solution of
3a. Since compounds 3 possess one stereogenic centre, the
hydrogen atoms of the CH2 group are diastereotopic. Thus they
resonate as an AB-quartet. Aromatic protons resonate between
6.85 and 7.52 ppm as multiplets. The C=S group resonance in
13C NMR spectra of 3a appears at 197.2 ppm. The 13C NMR
spectrum of 3a showed 11 distinct resonances in agreement
with the proposed structure. The mass spectrum of 3a dis-
played the molecular ion peak at m/z = 287. The IR spectrum
of compound 3a also supported the suggested structure, strong
absorption bands were observed at 3234 cm−1 for the OH
group. A tentative mechanism for this transformation is
proposed in Scheme 2.
It is reasonable to assume that compound 4 results from the
initial addition of carbon disulfide to the primary amines 2,
which react with phenacyl bromide 1 to produce 5. Intermedi-
ate 5 undergoes HBr elimination and cyclisation reaction to
generate 3.
We now report the three-component reaction between phen-
acyl bromide and primary amines in the presence of carbon
disulfide to afford the thiazolidine-2-thiones in good yields.
This method has the advantage that the reaction is performed
in neutral conditions and the starting materials can be mixed
without any activation nor modification.
Results and discussion
Reaction between phenacyl bromide 1 and primary amines 2
in the presence of carbon disulfide to afford the thiazolidine-2-
thiones 3 in high yields (Scheme 1).
The structures of compounds 3a–g were confirmed by IR,
1H NMR, 13C NMR and mass spectral data. Because of the
presence of an estereogenic centre in these molecules, the
hydrogen atoms of the CH2 group are diastereotopic.
Experimental
All melting points are uncorrected. Elemental analyses were per-
formed using a Heraeus CHN–O–Rapid analyser. Mass spectra were
recorded on a Finnigan-MAT 8430 mass spectrometer operating at an
ionisation potential of 70 eV. IR spectra were recorded on a Shimadzu
1
IR-470 spectrometer. H and 13C spectra were recorded on Bruker
DRX-500 Avance spectrometer in CDCl3 using TMS as the internal
standard or 85% H3PO4 as the external standard. Chemicals were
purchased from Fluka (Buchs, Switzerland) and were used without
further purification.
General procedure
Primary amine (1 mmol) was added dropwise to a magnetically stirred
solution of phenacyl bromide (1 mmol) and carbon disulfide (5 mmol)
at room temperature. The reaction mixture was then stirred for 24 h.
The solvent was removed under reduced pressure and the residue was
purified by silica gel column chromatography using hexane-ethyl
acetate as eluent. The solvent was removed under reduced pressure to
afford the product.
4-Hydroxy-3,4-diphenyl-thiazolidine-2-thione (3a):Yellow powder,
m.p. 137–139 °C, IR (KBr) (νmax cm−1): 3234, 1617, 1518, 1160, 1102.
Anal. Calcd for C15H13NOS2: C, 62.69; H, 4.56; N, 4.87. Found: C,
62.80; H, 4.43; N, 4.75%. MS (m/z, %): 287 (8). 1H NMR (500 MHz,
CDCl3): δ 4.28 (1H, d, 2JHH = 11.5 Hz, CH), 4.40 (1H, d, 2JHH = 11.5 Hz,
CH), 5.22 (1H, s, OH), 6.85–7.52 (10H, m, 10 CH aromatic) ppm.
13C NMR (125.8 MHz, CDCl3): δ 35.1 (CH2), 91.8 (C), 114.1, 119.3,
126.5, 127.2, 128.4, 129.7, 145.4 and 146.5 (aromatic moiety), 197.2
(C=S) ppm.
Scheme 1 Three-component reaction between carbon
disulfide, primary amines and phenacyl bromide.
3-(p-Tolyl)-4-hydroxy-4-phenyl-thiazolidine-2-thione (3b): Yellow
powder, m.p. 132–134 °C, IR (KBr) (νmax cm−1): 3230, 1614, 1511,
1165, 1108. Anal. Calcd for C16H15NOS2: C, 63.76; H, 5.02; N, 4.65.
* Correspondent. E-mail: ar_hasanabadi@yahoo.com

72 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 2 Suggested mechanism for formation of compound 3.
Found: C, 63.90; H, 5.15; N, 4.54%. MS (m/z, %): 301 (5). 1H NMR
(500 MHz, CDCl3): δ 2.34 (3H, s, Me), 3.95 (1H, d, 2JHH = 11.5 Hz,
CH), 4.15 (1H, d, 2JHH = 11.5 Hz, CH), 4.98 (1H, s, OH), 7.05 (2H, d,
3JHH= 8.1 Hz, 2CH), 7.24 (2H, d, 3JHH= 8.1 Hz, 2CH), 7.32–7.46 (5H,
m, 5CH aromatic) ppm. 13C NMR (125.8 MHz, CDCl3): δ 20.9 (CH3),
36.9 (CH2), 93.8 (C), 122.1, 126.4, 127.5, 129.3, 129.6, 133.5, 136.5
and 146.2 (aromatic moiety), 198.4 (C=S) ppm.
1196, 1158. Anal. Calcd for C10H11NOS2: C, 53.30; H, 4.92; N, 6.22.
Found: C, 53.22; H, 4.80; N, 6.15%. MS (m/z, %): 225 (7). 1H NMR
(500 MHz, CDCl3): δ 2.94 (3H, s, CH3N), 3.34 (1H, d, 2JHH = 11.5 Hz,
2
CH), 3.72 (1H, d, JHH = 11.5 Hz, CH), 5.60 (1H, s, OH), 7.31–7.62
(5H, m, 5CH aromatic) ppm. 13C NMR (125.8 MHz, CDCl3): δ 28.5
(NCH3), 37.4 (CH2), 95.1 (C), 126.7, 127.7, 129.3 and 146.1
(aromatic moiety), 196.4 (C=S) ppm.
3-(4-Nitrophenyl)-4-hydroxy-4-phenyl-thiazolidine-2-thione (3c):
Yellow powder, m.p. 140–142 °C, IR (KBr) (νmax cm−1): 3238, 1617,
1542, 1510, 1367, 1162, 1101. Anal. Calcd for C15H12N2O3S2:
C, 54.20; H, 3.64; N, 8.43. Found: C, 54.28; H, 3.50; N, 8.53%.
We gratefully acknowledge financial support from the Research
Council of Islamic Azad University of Zahedan of Iran.
1
MS (m/z, %): 332 (7). H NMR (500 MHz, CDCl3): δ 4.11 (1H, d,
2
2JHH = 11.5 Hz, CH), 4.35 (1H, d, JHH = 11.5 Hz, CH), 5.17 (1H, s,
Received 28 October 2012; accepted 5 December 2012
Paper 1201593 doi: 10.3184/174751912X13568926198645
Published online: 13 February 2013
3
3
OH), 7.56 (2H, d, JHH= 8.1 Hz, 2CH), 8.22 (2H, d, JHH= 8.1 Hz,
2CH), 7.3–7.40 (5H, m, 5CH aromatic) ppm. 13C NMR (125.8 MHz,
CDCl3): δ 37.4 (CH2), 94.6 (C), 119.8, 125.1, 126.2, 127.4, 129.3,
142.6, 146.2 and 148.7 (aromatic moiety), 198.8 (C=S) ppm.
References
3-(4-Bromophenyl)-4-hydroxy-4-phenyl-thiazolidine-2-thione (3d):
Yellow powder, m.p. 121–123 °C, IR (KBr) (νmax cm−1): 3218, 1605,
1514, 1162, 1100. Anal. Calcd for C15H12BrNOS2: C, 49.19; H, 3.30;
N, 3.82. Found: C, 49.30; H, 3.38; N, 3.71%. MS (m/z, %): 366 (4).
1
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94.5 (C), 119.4, 125.7, 126.4, 127.5, 129.3, 129.6, 135.6 and 145.7
(aromatic moiety), 198.5 (C=S) ppm.
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3-Benzyl-4-hydroxy-4-phenyl-thiazolidine-2-thione (3e): White
powder, m.p. 115–117 °C, IR (KBr) (νmax cm−1): 3205, 1598, 1487,
1152. Anal. Calcd for C16H15NOS2: C, 63.76; H, 5.02; N, 4.65.
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(500 MHz, CDCl3): δ 3.38 (1H, d, 2JHH = 11.5 Hz, CH), 3.67 (1H, d,
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2
2JHH = 11.5 Hz, CH), 4.42 (1H, d, JHH = 15.5 Hz, CH), 5.03 (1H, s,
2
OH), 5.44 (1H, d, JHH = 15.5 Hz, CH), 7.14–7.95 (10H, m, 10 CH
aromatic) ppm. 13C NMR (125.8 MHz, CDCl3): δ 37.2 (CH2), 48.4
(CH2), 94.5 (C), 126.4, 127.3, 127.8, 128.3, 128.9, 129.5, 135.3 and
145.7 (aromatic moiety), 198.6 (C=S) ppm.
3-Butyl-4-hydroxy-4-phenyl-thiazolidine-2-thione (3f): Yellow
powder, m.p. 112–114 °C, IR (KBr) (νmax cm−1): 3226, 1612, 1535,
1190, 1152. Anal. Calcd for C13H17NOS2: C, 58.39; H, 6.41; N, 5.24.
Found: C, 58.50; H, 6.55; N, 5.11%. MS (m/z, %): 267 (5). 1H NMR
(500 MHz, CDCl3): δ 1.31 (2H, m, CH2), 1.44 (3H, t, 3JHH= 7.05 Hz,
2
CH3), 1.51 (2H, m, CH2), 3.07 (1H, m, CHN), 3.36 (1H, d, JHH
=
11.5 Hz, CH), 3.70 (1H, d, 2JHH = 11.5 Hz, CH), 3.78 (1H, m, CHN),
5.67 (1H, s, OH), 7.28–7.55 (5H, m, 5 CH aromatic) ppm. 13C
NMR (125.8 MHz, CDCl3): δ 15.1 (CH3), 19.3 (CH2), 29.3 (CH2),
37.6 (CH2), 41.1 (NCH2), 95.4 (C), 126.8, 127.5, 129.1 and 146.2
(aromatic moiety), 196.7 (C=S) ppm.
3-Methyl-4-hydroxy-4-phenyl-thiazolidine-2-thione (3g): Yellow
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powder, m.p. 116–118 °C, IR (KBr) (νmax cm−1): 3195, 1610, 1537,