A facile and effective procedure for synthesis of polyfunctionalized pyrrolines from simultaneously stirring of carbon disulfide, aniline, arylglyoxals and β-enaminocarbonyls

Article abstract of DOI:10.1007/s13738-017-1166-1

An efficient one-pot synthesis of 2H-pyrroline derivatives by a four-component reaction between carbon disulfide, aniline, arylglyoxals and β-enaminocarbonyls in acetonitrile at room temperature under mild reaction conditions is reported. The addition rea

Full text of DOI:10.1007/s13738-017-1166-1

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1166-1
ORIGINAL PAPER
A facile and efective procedure for synthesis of polyfunctionalized
pyrrolines from simultaneously stirring of carbon disulfde,
aniline, arylglyoxals and β‑enaminocarbonyls
Mozhgan Masoudi1 · Mohammad Anary‑Abbasinejad2 · Alireza Maleki1
Received: 26 March 2017 / Accepted: 5 July 2017
© Iranian Chemical Society 2017
Abstract An efcient one-pot synthesis of 2H-pyrroline
derivatives by a four-component reaction between carbon
disulfde, aniline, arylglyoxals and β-enaminocarbonyls in
acetonitrile at room temperature under mild reaction con-
ditions is reported. The addition reaction has been done to
access broad range of 5-hydroxy-4-phenylcarbamodithioate
2-H pyrroline derivatives after about 6 h stirring. All reac-
tions were performed in acetonitrile at room temperature.
Reactions are clean, and products were isolated by simple
fltration.
powerful tools for the generation of chemical libraries, and
they have attracted signifcant attention due to their broad
applications in medicinal chemistry for the production of
diferent structural scafolds, and in combinatorial synthe-
sis [11–13]. N-substituted pyrrolines are an important class
of compounds which exhibit neuritogenic activity [14] and
serve as useful synthetic intermediates [15–17]. Organic
dithiocarbamates are utilized as substrates for radical
chemistry [18–20] and as synthetic intermediates toward
thiourea, guanidines and amidines [21–23]. The impor-
tance of the reactions of carbon disulfde with N-nucleo-
philes involves addition of carbon disulfde to N–H bonds
[24]. The products of these reactions, dithiocarbamate salts,
react with 2-chloro-1,3-dicarbonyl compounds [25], epox-
ides [26, 27], α-haloketones [28], and the other electron
defcient compounds that can be converted to dithiocarba-
mate derivatives. To the best of our knowledge, there has
not been any report on the reaction of carbon disulfde,
aniline, arylglyoxals and β-enaminocarbonyls. As part of
our ongoing project, to develop new synthetic methods for
nitrogen-containing heterocycles, we attempted to develop
a mild and efcient process for the synthesis of multisub-
stituted pyrroline. Herein, this paper reports a one-pot four-
component synthesis of 5-hydroxy-4-phenylcarbamodithio-
ate 2-H pyrroline derivatives from carbon disulfde, aniline,
arylglyoxals and β-enaminocarbonyls as starting materials
without using any catalysts (Scheme 1).
Keywords Four-component reaction · Pyrroline
derivatives · Arylglyoxals · β-Enaminocarbonyls
Introduction
In recent years, multicomponent reactions (MCRs) play
an important role in new primary synthetic chemistry in
the view of the fact that, these reactions increase the ef-
ciency by combination of several functional steps with-
out any changes of the conditions and isolation of inter-
mediates [1–10]. Multicomponent reactions (MCRs) are
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-017-1166-1) contains supplementary
material, which is available to authorized users.
* Mozhgan Masoudi
m.masoudi@iaurafsanjan.ac.ir;
masoudimozhgan@yahoo.co.in
Experimental procedures
1
Materials and characterization techniques
Young Researchers and Elite Club, Rafsanjan Branch,
Islamic Azad University, Rafsanjan, Iran
2
All the utilized arylglyoxals were synthesized by the
SeO2-oxidation of the related arylmethyl ketones on the
Department of Chemistry, Vali-e-Asr University,
Rafsanjan 77176, Iran
Vol.:(0123456789)
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J IRAN CHEM SOC
Scheme 1 Reaction between
carbon disulfde, aniline, arylg-
lyoxals and β-enaminocarbonyls
O
O
O
NHAr2
CH3CN
OH
or
PhNH2
+
+
CS2
Ar1
+
H3C
H3C
NHAr2
rt, 6h
OH
1
2
4m
4a-l
H3C
3
CH3
O
CH3
N Ar2
Ar1
O
S
H3C
N Ar2
HO Ar1
or
S
PhHN
S
PhHN
HO
5a-l
S
5m
basis of the reported procedure and used as their mono-
hydrates [29]. IR spectra were obtained on a Shimadzu
IR-470 spectrometer. The proton and carbon-13 NMR
spectra were recorded on Bruker DRX-400 Avance spec-
trometer at 400 and 100 MHz, respectively, with Me4Si as
an internal standard in DMSO. Elemental analyses (C, H,
N) were performed with a Heracus CHN-O-Rapid analyzer.
The chemicals used in this work purchased from Fluka
(Buchs, Switzerland) and were used without further purif-
cation. All the products were characterized using NMR and
IR spectral and analytical data.
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑phenyl‑4‑(phenylcar
bamodithioate)‑5‑(4‑nitrophenyl)‑1H‑pyrrol‑3yl)ethanone
(5b) Yield: 64%; yellow powder; m.p. 140–142 °C. IR
(KBr) (ῡmax, cm−1): 3372 (NH), 1598 (C=O). Calcd. for
(C26H23N3O4S2): C, 61.76; H, 4.59; N, 8.31%. Found: C,
1
61.69; H, 4.32; N, 8.15%. H NMR (CDCl3, 400 MHz):
δ = 2.12 (3H, s, CH3), 2.36 (3 H, s, CH3), 4.06 (1H, s, CH),
4.54 (1H, s, NH), 5.91 (1H, s, OH), 6.56–8.29 (m, aro-
matic hydrogens), 13C NMR (CDCl3, 100 MHz): δ = 15.4
(CH3), 29.9 (CH3), 51.3 (SCH), 70.5 (C–OH), 93.0, 147.0
(C=C), 110.7, 115.1, 120.8, 124.1, 126.3, 128.1, 128.8,
129.1, 129.6, 135.9 (aromatic carbons), 162.6 (C=S), 192.8
(C=O).
General procedure for synthesis of compounds 5a–m
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑phenyl‑4‑(phenylca
rbamodithioate)‑5‑(4‑fluorophenyl)‑1H‑pyrrol‑3yl)etha-
none (5c) Yield: 68%; white powder; m.p. 139–140 °C.
IR (KBr) (ῡmax, cm−1): 3276 (NH), 1603 (C=O). Calcd.
for (C26H23FN2O2S2): C, 65.25; H, 4.84; N, 5.85%. Found:
C, 65.39; H, 4.72; N, 5.75%. 1H NMR (CDCl3, 400 MHz):
δ = 2.10 (3H, s, CH3), 2.35 (3 H, s, CH3), 4.01 (1H, s, CH),
4.51 (1H, s, NH), 5.73 (1H, s, OH), 6.60–7.55 (m, aromatic
hydrogens), 13C NMR (CDCl3, 100 MHz): δ = 15.4 (CH3),
29.1 (CH3), 49.6 (SCH), 70.6 (C–OH), 93.4, 147.5 (C=C),
107.6, 115.1, 120.4, 127.0, 127.8, 128.9, 129.4, 136.3,
138.5 (aromatic carbons), 163.9 (C=S), 192.8 (C=O).
A solution of carbon disulfde (1 mmol), aniline (1 mmol),
β-enaminocarbonyls (1 mmol) and arylglyoxal monohy-
drates (1 mmol) in acetonitrile (3 ml) was stirred at room
temperature. After 6 h stirring, the resulting precipitate was
fltered, washed with acetonitrile (20 mL) to aford the pure
product.
Selected spectral data
1 ‑ ( 4 , 5 ‑ D i h y d ro ‑ 5 ‑ h y d rox y ‑ 2 ‑ m e t h y l ‑ 1 ‑ p h e -
nyl‑4‑(phenylcarbamodithioate)‑5‑phenyl‑1H‑pyrrol‑3yl)
ethanone (5a) Yield: 67%; yellow powder; m.p. 130–
132 °C. IR (KBr) (ῡmax, cm−1): 3374 (NH), 1594 (C=O).
Calcd. for (C26H24N2O2S2): C, 67.80; H, 5.25; N, 6.08%.
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑p‑tolyl‑4‑(phenylc
arbamodithioate)‑5‑(4‑fuorophenyl)‑1H‑pyrrol‑3yl)etha-
none (5d) Yield: 70%; gray powder; m.p. 150–152 °C.
IR (KBr) (ῡmax, cm−1): 3275 (NH), 1621 (C=O). Calcd.
for (C27H25FN2O2S2): C, 65.83; H, 5.12; N, 5.69%. Found:
C, 65.72; H, 5.02; N, 5.75%. 1H NMR (CDCl3, 400 MHz):
δ = 2.09 (3H, s, CH3), 2.31 (3 H, s, CH3), 2.33 (3 H, s,
CH3), 3.99 (1H, s, CH), 4.50 (1H, s, NH), 5.70 (1H, s, OH),
6.59–7.56 (m, aromatic hydrogens), 13C NMR (CDCl3,
100 MHz): δ = 14.8 (CH3), 20.6 (CH3), 28.5 (CH3), 50.0
(SCH), 70.1 (C–OH), 92.8, 146.9 (C=C), 106.8, 114.6,
1
Found: C, 67.69; H, 5.12; N, 6.15%. H NMR (d6-DMSO,
400 MHz): δ = 1.98 (3H, s, CH3), 2.27 (3 H, s, CH3), 4.60
(1H, s, CH), 5.76 (1H, s, NH), 6.34 (1H, s, OH), 6.75–7.40
(m, aromatic hydrogens), 13C NMR (d6-DMSO, 100 MHz):
δ = 15.4 (CH3), 29.9 (CH3), 52.5 (SCH), 68.0 (C–OH),
97.6, 148.9 (C=C), 110.9, 112.3, 112.4, 113.9, 115.6,
116.3, 128.4, 128.7, 129.1, 137.1 (aromatic carbons), 159.9
(C=S), 194.5 (C=O).
1 3

J IRAN CHEM SOC
1
114.9, 115.2, 120.0, 126.5, 126.6, 128.2, 128.9, 129.1,
133.0, 137.4 (aromatic carbons), 163.4 (C=S), 192.0
(C=O).
68.75; H, 5.65; N, 5.65%. H NMR (CDCl3, 400 MHz):
δ = 1.97 (3H, s, CH3), 2.42 (3H, s, CH3), 2.44 (3H, s, CH3),
3.96 (1H, d, 3JHH = 4 Hz, CH), 4.34 (1H, s, CH2), 4.36 (1H,
s, NH), 5.53 (1H, s, OH), 6.68–7.45 (m, aromatic). 13C
NMR (d6-DMSO, 100 MHz): δ = 8.8 (CH3), 16.0 (CH3),
23.5 (CH3), 49.0 (CH2), 64.2 (SCH), 71.6 (C–OH), 101.0,
142.5 (C=C), 109.7, 114.9, 119.9, 121.4, 122.0, 123.4,
124.2, 124.4, 132.9, 133.3, 133.5 (aromatic carbons), 159.2
(C=S), 187.0 (C=O).
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑p‑tolyl‑4‑(phenylcar
bamodithioate)‑5‑(4‑nitrophenyl)‑1H‑pyrrol‑3yl)ethanone
(5e) Yield: 65%; yellow powder; m.p. 155–157 °C. IR
(KBr) (ῡmax, cm−1): 3339 (NH), 1602 (C=O). Calcd. for
(C27H25N3O4S2): C, 62.41; H, 4.85; N, 8.09%. Found: C,
62.32; H, 5.02; N, 8.15%. 1H NMR (d6-DMSO, 400 MHz):
δ = 1.99 (3H, s, CH3), 2.17 (3 H, s, CH3), 2.24 (3 H, s,
CH3), 4.87 (1H, s, CH), 5.92 (1H, d, s, NH), 6.29 (1H,
s, OH), 6.77–7.78 (m, aromatic hydrogens), 13C NMR
(d6-DMSO, 100 MHz): δ = 15.3 (CH3), 20.9 (CH3), 28.7
(CH3), 52.6 (SCH), 68.5 (C–OH), 97.2, 147.4 (C=C),
108.6, 112.4, 116.1, 121.6, 128.3, 128.6, 129.7, 135.1,
136.4, 146.3, 146.7 (aromatic carbons), 160.0 (C=S), 193.3
(C=O).
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑benzyl‑4‑(phenylca
rbamodithioate)‑5‑(4‑fluorophenyl)‑1H‑pyrrol‑3yl)etha-
none (5i) Yield: 64%; gray powder; m.p. 121–122 °C.
IR (KBr) (ῡmax, cm−1): 3286 (NH), 1601 (C=O). Calcd.
for (C27H25FN2O2S2): C, 65.83; H, 5.12; N, 5.69%. Found:
C, 65.65; H, 5.34; N, 5.75%. 1H NMR (CDCl3, 400 MHz):
δ = 1.99 (3H, s, CH3), 2.43 (3H, s, CH3), 3.87 (1H, s, CH),
4.33 (1H, s, NH), 4.35 (1H, s, CH2), 5.58 (1H, s, OH),
6.63–7.55 (m, aromatic). 13C NMR (d6-DMSO, 100 MHz):
δ = 8.8 (CH3), 23.6 (CH3), 49.3 (CH2), 64.4 (SCH), 71.8
(C–OH), 108.7, 142.1 (C=C), 109.7, 109.9, 110.5, 110.7,
115.3, 120.1, 121.4, 121.8, 121.9, 122.1, 123.4, 124.3,
132.6 (aromatic carbons), 158.9 (C=S), 186.9 (C=O).
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑p‑tolyl‑4‑(phenylcarba
modithioate)‑5‑phenyl‑1H‑pyrrol‑3yl)ethanone (5f) Yield:
62%; white powder; m.p. 120–121 °C. IR (KBr) (ῡmax
,
cm−1): 3279 (NH), 1619 (C=O). Calcd. for (C27H26N2O2S2):
C, 68.32; H, 5.52; N, 5.90%. Found: C, 68.20; H, 5.43; N,
1
5.81%. H NMR (d6-DMSO, 400 MHz): δ = 2.08 (3H, s,
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑phenyl‑4‑(phenylca
rbamodithioate)‑5‑(2‑naphthyl)‑1H‑pyrrol‑3yl)ethanone
(5j) Yield: 64%; brown powder; m.p. 130–132 °C. IR
(KBr) (ῡmax, cm−1): 3286 (NH), 1624 (C = O). Calcd. for
(C30H26N2O2S2): C, 70.56; H, 5.13; N, 5.49%. Found: C,
CH3), 2.30 (3 H, s, CH3), 2.35 (3 H, s, CH3), 3.92 (1H, s,
CH), 4.51 (1H, s, NH), 5.64 (1H, s, OH), 6.61–7.56 (m, aro-
matic hydrogens), 13C NMR (d6-DMSO, 100 MHz): δ = 10.1
(CH3), 15.8 (CH3), 23.7 (CH3), 65.3 (SCH), 71.8 (C–OH),
105.7, 142.1 (C=C), 109.9, 115.2, 119.8, 121.7, 122.6, 122.7,
122.9, 123.0, 123.3, 123.5, 124.2, 124.3, 132.5 (aromatic car-
bons), 157.8 (C=S), 187.3 (C=O).
1
70.62; H, 5.24; N, 5.65%. H NMR (CDCl3, 400 MHz):
δ = 2.11 (3H, s, CH3), 2.42 (3H, s, CH3), 4.03 (1H, s, CH),
4.62 (1H, s, NH), 5.83 (1H, s, OH), 6.63–8.08 (m, aro-
matic). 13C NMR (CDCl3, 100 MHz): δ = 14.2 (CH3), 27.6
(CH3), 46.3 (CH2), 53.4 (SCH), 71.2 (C–OH), 96.7, 141.1
(C = C), 108.7, 109.3, 110.4, 110.6, 113.3, 115.8, 118.4,
119.9, 120.9, 121.1, 121.5, 122.3, 122.7, 123.4, 125.8 (aro-
matic carbons), 160.4 (C = S), 193.9 (C = O).
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑benzyl‑4‑(phenylcar
bamodithioate)‑5‑(4‑nitrophenyl)‑1H‑pyrrol‑3yl)ethanone
(5g) Yield: 66%; cream powder; m.p. 135–136 °C. IR
(KBr) (ῡmax, cm−1): 3280 (NH), 1617 (C=O). Calcd. for
(C27H25N3O4S2): C, 62.41; H, 4.85; N, 8.09%. Found: C,
1
62.35; H, 4.65; N, 8.15%. H NMR (CDCl3, 400 MHz):
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑butyl‑4‑(phenylcar
bamodithioate)‑5‑(4‑nitrophenyl)‑1H‑pyrrol‑3yl)ethanone
(5k) Yield: 71%; yellow powder; m.p. 110–112 °C. IR
(KBr) (ῡmax, cm−1): 3416 (NH), 1606 (C = O). Calcd. for
(C24H27N3O4S2): C, 59.36; H, 5.60; N, 8.65%. Found: C,
δ = 1.98 (3H, s, CH3), 2.44 (3H, s, CH3), 3.93 (1H, d,
3
3JHH = 4 Hz, CH), 4.35 (1H, d, JHH = 4 Hz, CH2), 4.38
(1H, s, NH), 5.57 (1H, s, OH), 6.67–7.41 (m, aromatic).
13C NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 28.8 (CH3),
46.0 (CH2), 47.9 (SCH), 69.4 (C–OH), 93.7, 141.7 (C=C),
106.2, 115.0, 120.2, 125.2, 126.7, 127.3, 128.6, 128.7,
129.0, 129.4, 138.1 (aromatic carbons), 164.4 (C=S), 192.3
(C=O).
1
59.48; H, 5.49; N, 8.45%. H NMR (CDCl3, 400 MHz):
3
δ = 0.78 (3H, t, JHH = 8 Hz, CH3), 1.21 (2H, m,
3JHH = 8 Hz, CH2), 1.51 (2H, m, JHH = 8 Hz, CH2), 2.08
3
3
(3H, s, CH3), 2.56 (3H, s, CH3), 2.75 (2H, t, JHH = 8 Hz,
CH2), 4.48 (1H, s, CH), 6.55 (1H, s, NH), 6.88 (1H, s, OH),
7.27–8.30 (m, aromatic). 13C NMR (CDCl3, 100 MHz):
δ = 12.2 (CH3), 13.6 (CH2), 16.3 (CH3), 19.4 (CH3), 31.1
(CH2), 44.2 (CH2), 60.7 (SCH), 73.7 (C–OH), 101.0, 145.3
(C = C), 110.0, 123.1, 123.8, 124.4, 127.5, 129.7, 132.6,
136.9 (aromatic carbons), 164.5 (C = S), 194.5 (C = O).
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑benzyl‑4‑(phenylca
rbamodithioate)‑5‑p‑tolyl‑1H‑pyrrol‑3yl)ethanone
(5h) Yield: 60%; white powder; m.p. 120–122 °C. IR
(KBr) (ῡmax, cm−1): 3273 (NH), 1600 (C=O). Calcd. for
(C28H28N2O2S2): C, 68.82; H, 5.78; N, 5.73%. Found: C,
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J IRAN CHEM SOC
Table 1 Reaction between carbon disulfde, aniline, arylglyoxals and
β-enaminocarbonyls
1‑(4,5‑Dihydro‑5‑hydroxy‑2‑methyl‑1‑butyl‑4‑(phenylca
rbamodithioate)‑5‑(4‑phenyl)‑1H‑pyrrol‑3yl)ethanone
(5l) Yield: 69%; white powder; m.p. 90–93 °C. IR
(KBr) (ῡmax, cm−1): 3417 (NH), 1584 (C = O). Calcd. for
(C24H28N2O2S2): C, 65.42; H, 6.41; N, 6.36%. Found: C,
5
Ar1
Ar2
Yielda (%)
a
b
c
d
e
f
C6H5
C6H5
C6H5
C6H5
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
C6H4CH2
C6H4CH2
C6H4CH2
C6H5
67
64
68
70
65
62
66
60
64
64
71
69
62
4-NO2C6H4
4-FC6H4
4-FC6H4
4-NO2C6H4
C6H5
4-NO2C6H4
4-CH3C6H4
4-FC6H4
2-Naphtyl
4-NO2C6H4
C6H5
1
66.58; H, 6.23; N, 6.25%. H NMR (CDCl3, 400 MHz):
3
δ = 0.77 (3H, t, JHH = 8 Hz, CH3), 0.90 (2H, m,
3JHH = 8 Hz, CH2), 1.85 (3H, s, CH3), 2.08 (3H, s, CH3),
2.33 (2H, m, 3JHH = 8 Hz, CH2), 4.66 (2H, t, 3JHH = 8 Hz,
CH2), 4.76 (1H, s, CH), 6.63 (1H, s, NH), 7.14 (1H, s, OH),
7.28–7.48 (m, aromatic). 13C NMR (CDCl3, 100 MHz):
δ = 13.7 (CH3), 16.1 (CH2), 19.5 (CH3), 20.0 (CH3), 29.0
(CH2), 31.5 (CH2), 44.0 (SCH), 64.1 (C–OH), 102.1, 135.6
(C = C), 125.8, 127.7, 128.3, 128.6, 128.8, 129.1, 129.3,
129.4, 129.5 (aromatic carbons), 164.5 (C = S), 194.5
(C = O).
g
h
i
j
k
l
C4H9
C4H9
4-CH3C6H4
m
4-CH3C6H4
2 , 3 , 4 , 5 , 6 , 7 ‑ H ex a h y d ro ‑ 2 ‑ h y d rox y ‑ 6 , 6 ‑ d i m e -
thyl‑4‑oxo‑1,2‑dip‑tolyl‑1H‑indol‑3‑ylphenylcarbamodith-
ioate (5m) Yield: 62%; pink powder; m.p. 140–142 °C.
IR (KBr) (ῡmax, cm−1): 3300 (NH), 1606 (C = O). Calcd.
for (C31H32N2O2S2): C, 70.42; H, 6.10; N, 5.30%. Found:
C, 70.53; H, 5.24; N, 5.42%. 1H NMR (CDCl3, 400 MHz):
δ = 0.66, 0.98, 2.36, 2.40 (12H, s, 4CH3), 1.12, 1.13
(4H, s, 2CH2), 3.65 (1H, s, CH), 4.97 (1H, s, NH), 5.48
(1H, s, OH), 6.64–7.31 (m, aromatic). 13C NMR (CDCl3,
100 MHz): δ = 21.0, 26.9, 28.9, 29.0 (4CH3), 28.2 (C),
32.2, 34.3 (2CH2), 50.1 (SCH), 69.3 (C–OH), 96.5, 144.6
(C = C), 125.1, 125.6, 127.4, 128.6, 129.1, 129.2, 129.5,
129.8, 131.9, 133.8, 135.1 (aromatic carbons), 162.3
(C = S), 193.1 (C = O).
Conditions: MeCN, rt, 6 h
aIsolated yield
We also examined the reaction in the presence of 2 ml
ethanol instead of acetonitrile, but the expected 5-hydroxy-
4-phenylcarbamodithioate 2-H pyrroline derivatives were
not obtained in good yields. When aliphatic amines such
as benzyl amine were used instead of aniline as amine
component, it was observed that the reaction was done in
this style after 3 h; however, due to the formation of by-
products, the corresponding 5-hydroxy-4-phenylcarbamo-
dithioate 2-H pyrrolines were obtained in low yields, and
the removal of impurities was very difcult. We tried to
investigate the reaction in the presence of substituted ani-
lines such as 2,4-xylidine instead of aniline in the reaction
conditions, but product is not obtained in good yield. So,
the reaction was investigated with aniline instead of ali-
phatic amines or substituted anilines. Then, we examined
the infuence of diferent temperatures on a typical reaction
for synthesis of 5a. To our satisfaction, when the reaction
was carried out at room temperature in 6 h, the product
was 67% yield but at refux conditions in the same time
the product was 30% yield. To investigate the generality of
the reaction, diferent arylglyoxals with electron donor and
electron withdrawing groups were treated with aromatic
and aliphatic enaminocarbonyls and the related 5-hydroxy-
4-phenylcarbamodithioate 2-H pyrroline derivatives were
Results and discussion
In a typical reaction, at frst carbon disulfde was reacted
with aniline in acetonitrile. After 2 min stirring, phenyl-
glyoxal and 4-phenylamino-3-pentene-2-one were added
to it. The reaction course was monitored by TLC. After
6 h stirring, the starting materials were disappeared on
TLC and one-pot appeared which identifed to be the pyr-
roline derivative 5a. Compound 5a was isolated as a yel-
low solid in 67% yield to ofer the highly pure product
(Scheme 2).
Scheme 2 A typical reac-
tion between carbon disulfde,
aniline, 3a and 4a
O
S
CH3
O
H3C
PhHN
O
NHPh
CH3CN
rt, 6h
N Ph
Ph
OH
PhNH2
+
+
CS2
+
Ph
HO
5a
OH
S
1
2
4a
3a
1 3

J IRAN CHEM SOC
O
SH
S
SH
O
PhHN
S C S
+
NHAr2
PhNH2
PhHN
Ar1
S
6
2
1
S
PhHN
O
8
O
O
NHAr2
O
O
O
S
NAr2
-H2O
NHAr2
OH
Ar1
+
Ar1
O
Ar1
OH
OH
NHAr2
Ar1
4a-l
7
3
S
HO
5a-l
PhHN
S
Scheme 3 Suggested mechanism for formation of 5-hydroxy-4-phenylcarbamodithioate 2-H pyrroline derivatives 5a–l
obtained in acetonitrile at room temperature after 6 h stir-
ring and the products were simply isolated by fltration and
washing with acetonitrile. All the reactions were observed
to produce good yields (60–71%) compared to other exist-
ing procedures. The outcome was listed in Table 1. This
process has many advantages such as high efciency, selec-
tivity, easy separation, purifcation, and mild reaction con-
ditions. They are not only environmentally benign, but also
economically benefcial because toxic wastes can be mini-
mized or eliminated. All these facts have prompted us to
achieve the multicomponent synthesis of 5-hydroxy-4-phe-
nylcarbamodithioate 2-H pyrrolines 5a–m at room temper-
ature by the mentioned method. All the products shown in
Table 1 are stable solids, and the structure of compounds
5a–m was deduced from their spectral and analytical data.
closure by intramolecular attack of nitrogen to carbonyl
group of arylglyoxal to aford the related pyrroline ring 5.
Conclusions
In summary, we report herein the reaction between carbon
disulfde, aniline, arylglyoxals and β-enaminocarbonyls in
the absence of any catalysts to aford 5-hydroxy-4-phenyl-
carbamodithioate 2-H pyrroline derivatives in good yields.
The advantages of this method are readily available starting
materials, neutral reaction conditions, catalyst-free, simple
isolation and purifcation of products.
Acknowledgements We gratefully acknowledge, Islamic Azad Uni-
versity, Rafsanjan branch for fnancial support.
1
For example, the H NMR spectrum of 5a exhibited two
singlets at 1.98 and 2.27 ppm for two methyl groups. The
CH of pyrroline ring was observed as a singlet at 4.60 ppm.
Two singlets at 5.76, and 6.34 ppm are for NH and OH pro-
tons, respectively. The aromatic protons resonated between
6.75 and 7.40 ppm. 13C NMR spectrum of 5a showed ten
distinct signals for aromatic carbons in consistent with the
proposed structure, thiocarbonyl and carbonyl resonating at
159.9 and 194.5 ppm, respectively. The structure of com-
pound 5a was also confrmed by its IR spectrum, which
exhibited two absorption bands at 1594 and 3374 cm−1 are
for C = O and NH groups, respectively.
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