Reactions of diphenacylaniline and diphenacyl sulfide under Gewald conditions: Generation of enamines and thioamides

Article abstract of DOI:10.1039/c3ra21556c

The 1,5-diketone, diphenacylaniline, yielded an enamine under Gewald conditions, while another 1,5-diketone, diphenacyl sulfide, resulted in thioamide formation under identical conditions. 2-Amino-4-(3-oxo-1,3- diphenylpropyl)-4,5,6,7-tetrahydrobenzo[b]th

Full text of DOI:10.1039/c3ra21556c

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Reactions of diphenacylaniline and diphenacyl sulfide
under Gewald conditions: generation of enamines and
thioamides3
Cite this: DOI: 10.1039/c3ra21556c
Nidhin Paul, Ramalingam Sathishkumar, Chellathurai Anuba
and Shanmugam Muthusubramanian*
Received 25th July 2012,
The 1,5-diketone, diphenacylaniline, yielded an enamine under Gewald conditions, while another 1,5-
diketone, diphenacyl sulfide, resulted in thioamide formation under identical conditions. 2-Amino-4-(3-
oxo-1,3-diphenylpropyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile was obtained from the 1,5-
diketone 2-(3-oxo-1,3-diphenylpropyl)-1-cyclohexanone under the same conditions.
Accepted 13th March 2013
DOI: 10.1039/c3ra21556c
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3 connected by an N-aryl group, and/or the monothiophene 4
(Scheme 1). Accordingly, targeting the bisthiophene 3, a
Introduction
The Gewald reaction is the most convenient and well-
established protocol for the synthesis of 2-aminothiophenes,1
and it involves the three-component domino reaction of a
ketone with an activated nitrile and elemental sulfur in the
presence of a base. 2-Aminothiophenes serve as important
intermediates in dye preparation, in the pharmaceutical
industry and as the basic framework for a variety of natural
products.2 In addition, this transformation is remarkable, as it
is among the few organic reactions which involve the
incorporation of elemental sulfur at ambient temperature.
The plan of this investigation was to generate bis-thiophene
linked by a heteroatom X (X = S or NAr) from the Gewald
reaction of appropriate 1,5-diketones and the interesting
results of this investigation are described in this article.
mixture of diphenacyl aniline 1, malononitrile and sulfur
was formed in a 1 : 2 : 2 ratio and treated with a small amount
of piperidine. On completion of the reaction, the base was
removed and the product was extracted with dichloromethane.
The generality of the reaction was tested with differently
substituted diphenacylanilines and in all the cases, only one
product (5) was obtained in 50–65% yield (Scheme 1, Table 1).
It should be mentioned that the monophenacylaniline, on
treatment with base at elevated temperatures, was found to
yield the enamine 5. But at room temperature, only in the
presence of malononitrile and sulfur does 1 undergo the
reaction to produce 5.
Preliminary elemental analysis indicates the presence of
nitrogen and the absence of sulfur in 5, and the structural
identity of 5 has been established by NMR and single crystal
X-ray analysis (Fig. 1).7
Results and discussion
The formation of 5 from the reaction of diphenacylaniline
with malononitrile and sulfur is surprising as neither is
incorporated into the product. A closer analysis indicates that
Heterocycles with one or more heteroatoms are traditionally
synthesised from their acyclic counterparts.3 In continuation
of our interest in generating heterocycles from acyclic
systems,4 especially from 1,5-diketones, we planned to
synthesize compounds with two thiophene nuclei joined by
an intervening nitrogen or sulfur atom from substituted
diphenacylanilines 1 and diphenacyl sulfides 2 respectively.
Attempted Gewald reaction of diphenacylanilines 1: The
Gewald reaction of 1 is expected to generate the bis-thiophene
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj
University, Madurai 625 021, India. E-mail: muthumanian2001@yahoo.com;
Fax: +91-452-2459845; Tel: +91-452-2459845
Electronic supplementary information (ESI) available. CCDC reference number
3
Scheme 1 Reaction of 1 under Gewald conditions.
836390. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3ra21556c
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Table 1 Yields and melting points of 5
Entry
Ar
Ar9
Yielda (%)
m.p. (uC)
5a
5b
5c
5d
5e
5f
5g
5h
5i
C6H5
C6H5
C6H5
C6H5
4-Me-C6H4
4-Me-C6H4
4-Me-C6H4
4-Cl-C6H4
4-Cl-C6H4
C6H5
52
42
59
43
45
54
40
61
45
126 (126–127)5
145 (144–145)5
162
4-Me-C6H4
4-F-C6H4
4-Cl-C6H4
C6H5
4-F-C6H4
4-Me-C6H4
C6H5
183 (149–150)6
140 (141–142)5
189
161
Scheme 3 Reaction of 2 under Gewald conditions.
166 (170–171)6
171
4-Me-C6H4
a
Isolated yield after purification by column chromatography.
(41%) in the case of 5a, when ethyl cyanoacetate was used
instead of malononitrile. It is worth mentioning that 1,4-
diaryl-2-(arylamino)but-2-ene-1,4-diones 5 are important pre-
cursors for the synthesis of heterocyclic compounds, and
several methods for their preparation are reported in the
literature.8
Attempted Gewald reaction of diphenacyl sulfides 2: Having
observed an interesting rearrangement in the case of 1 under
Gewald conditions, our attention was shifted to another
related system, diphenacylsulfide 2, a 1,5-diketone with an
intervening sulfur. 2 is expected to generate the bis-thiophene
6 connected by a sulfur atom, or the monothiophene 7
(Scheme 3).
Fig. 1 ORTEP diagram of 5b showing the atom numbering scheme and
displacement ellipsoids drawn at the 50% probability level.
Accordingly, one mole of diphenacyl sulfide 2, two moles of
malononitrile and elemental sulfur were mixed together, along
with piperidine. The course of the reaction was monitored by
TLC and it was found that an increase in the proportion of
piperidine reflected in an increase in the disappearance of 2,
and 2 reacted completely with one equivalent of the base. The
reaction mass was extracted with dichloromethane and
purified through column chromatography to obtain two
products, thioamide 8 as the major product and thiophene 9
as the minor product (Scheme 3).
The reaction did not proceed in the absence of malononi-
trile, even with a higher proportion of base or on heating. In
order to generalise this reaction, different organic bases such
as pyrrolidine and morpholine were used, and quantitative
yields of thioamides incorporating the corresponding bases
were obtained (Table 2). The reaction did not proceed when
diethylamine or sodium ethoxide were used. The minor
product, thiophene 9, was separated and characterized only
in the parent diphenacyl sulfide and found to be present in
other cases in trace amounts, as evidenced from the crude
NMR spectra. The nonequivalence of the C2 and C6 (and the
C3 and C5) carbons in 8a suggests that the restricted rotation
of the amide bond, although ring flipping makes the
methylene hydrogens equivalent.
the reaction has ultimately led to
compound 1 with the loss of a hydrogen molecule.
a rearrangement of
Interestingly, in the absence of sulfur or malononitrile, the
reaction does not proceed. It is clear that both sulfur and
malononitrile are involved in the reaction, but are not
incorporated into the product. It is worth mentioning that
monophenacylaniline does not undergo any reaction under
identical conditions. Based on these facts, a mechanism can
be suggested, in which the initially formed Knoevenagel
adduct increases the acidity of the a-H (Scheme 2). Once the
carbon is thiolated, instead of attacking the cyanide, it is
displaced by an internal nucleophilic displacement. A sub-
sequent ring opening leads to the product 5. In the course of
the reaction, the Knoevenagel adduct hydrolyses back to the
carbonyl compound. The reaction proceeded with a lower yield
A tentative mechanism has been proposed for the forma-
tion of the thioamide and the simple thiophene (Scheme 4).10
As the mechanism suggests PhCOCH2S2 to be a leaving group
during the reaction (Scheme 4),11 it can be anticipated that any
–SR group could leave, yielding the thioamide. Therefore, we
planned to carry out the reaction with different PhCOCH2SX
species in place of diphenacyl sulfide. In each case, as
Scheme 2 Proposed mechanism for the formation of 5.
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Table 2 Yields and melting points for thioamide
Entry
X
YH
Yielda (%)
m.p. (uC)
Scheme 5 Gewald reaction of 10.
8a
8b
8c
8d
8e
8f
8g
8h
8i
H
Piperidine
Piperidine
Piperidine
Piperidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Morpholine
Morpholine
Morpholine
84
77
87
85
80
88
84
78
87
79
86
78
4-Me
4-OMe
4-Cl
H
4-Me
4-Cl
4-OMe
H
86 (88–89)9a
97
121 (121–124)9a
117
124
118
110
addition of cyclohexanone with substituted chalcones by a
known method.15 Preliminary TLC analysis of the crude
mixture indicates the formation of a single product. The one
and two dimensional NMR analysis of the isolated product
indicates the formation of the monothiophene, 2-amino-4-(3-
oxo-1,3-diphenylpropyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-
3-carbonitrile 11 in 74% yield (Scheme 5). The fact that the free
carbonyl carbon at 198.6 ppm has a HMBC contour with the
aryl hydrogens at 7.89 ppm clearly shows that the thiophene
formation has occurred at the cyclohexyl system, leaving the
side chain unaffected. The mass spectrum of 11 has a
molecular ion at m/z 409.33 [M + 23] (calcd. 386.14 [M+]).
It should be mentioned that 1,3,5-triphenyl-1,5-pentadione
was subjected to identical reaction conditions, but neither the
bis- nor the monothiophene were formed, resulting in the
recovery of the starting material.
Thus it is observed that 1,5-diketones with methylene
groups only at the 2 and 4 positions are not reactive enough
towards Gewald cyclisation. The initially formed Knoevenagel
adduct fails to undergo subsequent reaction, leaving the
adduct to be in equilibrium with the diketone. In 10, it can be
seen that it is not the methylene at the 2 or 4 positions that has
been involved in the reaction, but that at the 6 position. If
steric reasons are attributed to the failure of the methylene at
the 2 or 4 positions to participate in the reaction, it is not clear
why formation of the monothiophene is also not favored. It is
probable that the attacks outlined in Schemes 2 and 4 may be
competent enough in the cases of 1 and 2, preventing the
system from undergoing the conventional Gewald reaction,
ultimately yielding the abnormal products.
111 (112–113)9b
116
8j
8k
4-Me
4-OMe
120 (122–124)9c
a
Isolated yield after purification by column chromatography.
expected, the thioamide 8a was obtained in a very good yield
(the yields for the different chosen X groups: phenyl (80%),
cyclohexyl (76%), benzimidazoyl (80%), benzoxazolyl (78%) or
2-phenyltetrazolyl (83%)), supporting the mechanism.
Thioamides are a special group of compounds with varied
chemical reactivity and biological activity.12 Even though
several methods for the preparation of thioamides are
available in the literature,13 reports related to a-ketothioa-
mides are limited.9,14
Attempted Gewald reaction on 2-(3-oxo-1,3-diphenylpropyl)-1-
cyclohexanone 10: The unexpected reactions leading to
different products with two different 1,5-diketones prompted
us to apply the same reaction conditions to another diketone,
a diastereomerically pure, racemic 2-(3-oxo-1,3-diphenylpro-
pyl)-1-cyclohexanone 10, obtained via
a simple Michael
Conclusion
In conclusion, it is shown that different diketones under
Gewald reaction conditions unexpectedly give a wide variety of
products. The diketones with nitrogen at the 3 position under
Gewald conditions rearrange to 1,4-diketones, while those
with sulfur provide thioamides. Diketones without any
heteroatom provide an aminothiophene at one end, while
keeping the other keto group intact.
Scheme 4 Mechanism for the formation of thioamide 8 and thiophene 9.
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CDCl3): dC 95.6, 122.9, 127.4, 128.5, 128.8, 129.3, 129.7, 130.4,
132.1, 134.5, 134.6, 137.4, 138.8 156.3, 191.2, 191.9.
Experimental section
Melting points were measured in open capillary tubes and are
1
uncorrected. The H, 13C and 2D NMR spectra were recorded
2-(Phenylamino)-1,4-di-p-tolylbut-2-ene-1,4-dione (5e)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.37 (s, 3H), 2.39 (s, 3H), 6.07 (s, 1H), 6.98–7.00 (m, 3H), 7.12–
7.30 (m, 7H), 7.81–7.92 (m, 3H), 12.59 (s, 1H); 13C NMR (75
MHz, CDCl3): dC 21.5, 21.7, 94.8, 121.5, 124.8, 127.4, 127.9,
129.2, 129.5, 129.9, 132.2, 136.4, 138.8, 142.5, 145.5, 156.7,
190.7, 191.8.
on a Bruker (Avance) 300 MHz NMR instrument using TMS as
an internal standard and CDCl3 as the solvent. Standard
Bruker software was used throughout. Chemical shifts are
given in parts per million (d-scale) and the coupling constants
are given in Hertz. Silica gel-G plates (Merck) were used for
TLC analysis with a mixture of petroleum ether (60–80 uC) and
ethylacetate as the eluant. Electrospray ionisation mass
spectrometry (ESI-MS) analysis was performed in the positive
ion mode on a liquid chromatography-ion trap mass spectro-
meter (LCQ Fleet, Thermo Fisher Instruments Limited, US).
Elemental analyses were performed on a Perkin Elmer 2400
Series II Elemental CHNS analyzer.
2-(4-Fluorophenylamino)-1,4-di-p-tolylbut-2-ene-1,4-dione (5f)
Isolated as colorless solid; 1H NMR (300 MHz, CDCl3): dH 2.38
(s, 3H), 2.40 (s, 3H), 6.07 (s, 1H), 6.81–6.87 (m, 2H), 6.92–6.97
(m, 2H), 7.20–7.26 (m, 4H), 7.81–7.87 (m, 4H), 12.49 (s, 1H);
13C NMR (75 MHz, CDCl3): dC 21.5, 21.8, 94.8, 116.0 (d, J = 22.5
Hz), 123.7 (d, J = 7.5 Hz), 127.5, 129.2, 129.5, 129.8, 132.3,
135.1, 136.4, 142.6, 145.6, 157.1, 159.0 (d, J = 240.0 Hz), 190.9,
191.6. Anal. calcd for C24H20FNO2: C, 77.19; H, 5.40%; N, 3.75.
Found C, 77.16; H, 5.37; N, 3.71%.
General procedure for the synthesis of 1,4-diaryl-2-
(arylamino)but-2-ene-1,4-diones (5)
1,4-Diaryl-2-(arylamino)but-2-ene-1,4-diones (5) were prepared
by mixing substituted 2-[(2-oxo-2-arylethyl)anilino]-1-aryl-1-
ethanones (1), elemental sulfur and malononitrile in a molar
ratio of 1 : 2 : 2, and then adding a few drops of piperidine
and leaving the reaction mixture at room temperature without
any solvent for five minutes. On completion of the reaction, as
indicated by TLC, the mixture was washed with cold water and
the residue was extracted with dichloromethane in order to
remove the excess sulfur. The extract was dried and purified by
column chromatography (petroleum ether–ethylacetate) using
(60–120 mesh) silica gel.
1,4-Di-p-tolyl-2-(p-tolylamino)but-2-ene-1,4-dione (5g)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.23 (s, 3H), 2.38 (s, 3H), 2.39 (s, 3H), 6.02 (s, 1H), 6.86–6.96
(m, 4H), 7.20–7.26 (m, 4H), 7.81–7.90 (m, 4H), 12.55 (s, 1H);
13C NMR (75 MHz, CDCl3): dC 20.7, 21.5, 21.8, 94.2, 121.6,
127.4, 129.1, 129.4, 129.8, 129.9, 132.2, 134.6, 136.2, 136.5,
142.4, 145.5, 157.0, 190.5, 191.8. Anal. calcd for C25H23NO2: C,
81.27; H, 6.27; N, 3.79%. Found C, 81.23; H, 6.22; N, 3.75%.
1,4-Bis(4-chlorophenyl)-2-(phenylamino)-but-2-ene-1,4-dione
(5h)
1,4-Diphenyl-2-(phenylamino) but-2-ene-1,4-dione (5a)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
6.11 (s, 1H), 6.96–7.01 (m, 3H), 7.12–7.17 (m, 2H), 7.38–7.57
(m, 6H), 7.92–7.99 (m, 4H), 12.60 (s, 1H); 13C NMR (75 MHz,
CDCl3): dC 94.9, 121.7, 125.0, 127.3, 128.4, 128.7, 129.2, 129.6,
131.9, 134.3, 134.6, 138.5, 138.8, 156.7, 190.9, 192.1.
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
6.05 (s, 1H), 6.94–7.03 (m, 3H), 7.13–7.18 (m, 2H), 7.34–7.42
(m, 4H), 7.85–7.89 (m, 4H), 12.56 (s, 1H); 13C NMR (75 MHz,
CDCl3): dC 94.5, 121.8, 125.4, 128.7 (2C), 128.8, 129.1, 129.4,
130.8, 132.8, 137.0, 138.3, 140.9, 156.5, 189.7, 190.9.
1,4-Diphenyl-2-(p-tolylamino)but-2-ene-1,4-dione (5b)
1,4-Bis(4-chlorophenyl)-2-(p-tolylamino)but-2-ene-1,4-dione
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.19 (s, 3H), 6.07 (s, 1H), 6.86–6.95 (m, 4H), 7.38–7.57 (m, 6H),
7.91–7.99 (m, 4H), 12.52 (s, 1H); 13C NMR (75 MHz, CDCl3): dC
20.7, 94.3, 121.9, 127.3, 128.4, 128.7, 129.7, 129.8, 131.8, 134.2,
134.7, 134.9, 136.0, 139.0, 157.1, 190.8, 192.2.
(5i)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.38 (s, 3H), 5.99 (s, 1H), 7.24–7.46 (m, 6H), 7.82–8.04 (m, 6H),
12.48 (s, 1H); 13C NMR (75 MHz, CDCl3): dC 23.7, 94.0, 120.0,
122.0, 127.8, 128.7, 129.2, 129.7, 129.9, 130.9, 131.3, 132.9,
140.1, 141.2, 157.1, 190.9, 191.8. Anal. calcd for C23H17Cl2NO2:
C, 67.33; H, 4.18; N, 3.41%. Found C, 67.30; H, 4.14; N, 3.38%.
2-(4-Fluorophenylamino)-1,4-diphenylbut-2-ene-1,4-dione (5c)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
6.12 (s, 1H), 6.80–6.85 (m, 2H), 6.93–6.97 (m, 2H), 7.37–7.57
(m, 6H), 7.91–7.96 (m, 4H), 12.65 (s, 1H); 13C NMR (75 MHz,
CDCl3): dC 94.7, 116.0 (d, J = 22.5 Hz), 123.8 (d, J = 7.5 Hz),
127.3, 128.4, 128.7, 129.5, 131.9, 134.4, 134.5, 134.7, 138.7,
156.9, 160.0 (d, J = 240.0 Hz), 191.0, 192.0. Anal. calcd for
C22H16FNO2: C, 76.51; H, 4.67; N, 4.06%. Found C, 76.47; H,
4.63; N, 4.03%.
General procedure for the synthesis of 1-aryl-2-piperidino/
pyrrolyl/morpholino-2-thioxo-1-ethanone (8)
Thioamides (8) were prepared by mixing the substituted 2,2’-
thiobis(1-arylethanone) (2), elemental sulfur and malononi-
trile in a molar ratio of 1 : 2 : 2 and then adding piperidine/
pyrrolidine/morpholine in drops. The reaction mixture was left
at room temperature for a few minutes and extracted with
dichloromethane, and the sulfur was filtered off. The extract
was purified by column chromatography using (60–120 mesh)
silica gel.
2-(4-Chlorophenylamino)-1,4-diphenylbut-2-ene-1,4-dione (5d)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
6.13 (s, 1H), 6.88–6.93 (m, 2H), 7.09–7.13 (m, 2H), 7.37–7.60
(m, 6H), 7.91–7.98 (m, 4H), 12.55 (s, 1H); 13C NMR (75 MHz,
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23] (calcd. 276.03 [M + 23]). Anal. calcd for C12H12ClNOS: C,
56.80; H, 4.77; N, 5.52%. Found C, 56.77; H, 4.72; N, 5.47%.
1-Phenyl-2-piperidino-2-thioxo-1-ethanone (8a)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
1.62–1.83 (m, 6H, 3CH2), 3.54 (t, 2H, J = 5.4 Hz, CH2), 4.24 (t,
2H, J = 6.0 Hz, CH2), 7.49 (t, 2H, J = 7.2 Hz, Ar–H), 7.59 (t, 1H, J
= 7.2 Hz, Ar–H), 7.99 (d, 2H, J = 7.2 Hz, Ar–H); 13C NMR (75
MHz, CDCl3): dC 23.9, 25.3, 26.3, 48.0, 52.9, 128.7, 129.7, 133.3,
134.1, 187.9, 194.2. Anal. calcd for C13H15NOS: C, 66.92; H,
6.48; N, 6.00%. Found C, 66.88; H, 6.44; N, 5.97%.
1-(4-Methoxyphenyl)-2-tetrahydro-1H-1-pyrrolyl-2-thioxo-1-
ethanone (8h)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.02–2.10 (m, 4H, 2CH2), 3.54 (t, 2H, J = 6.9 Hz, CH2), 3.88 (s,
3H, OCH3), 3.95 (t, 2H, J = 6.9 Hz, CH2), 6.95 (d, 2H, J = 9 Hz,
Ar–H), 7.97 (d, 2H, J = 9 Hz, Ar–H); 13C NMR (75 MHz, CDCl3):
dC 23.9, 26.1, 51.0, 51.2, 55.6, 114.1, 126.1, 132.5, 164.5, 188.1,
193.3. Anal. calcd for C13H15NO2S: C, 62.62; H, 6.06; N, 5.62%.
Found C, 62.59; H, 6.02; N, 5.59%.
1-(4-Methylphenyl)-2-piperidino-2-thioxo-1-ethanone (8b)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
1.61–1.80 (m, 6H, 3CH2), 2.46 (s, 3H, CH3), 3.51 (br s, 2H,
CH2), 4.24 (br s, 2H, CH2), 7.28 (d, 2H, J = 8.1 Hz, Ar–H), 7.88
(d, 2H, J = 8.1 Hz, Ar–H); 13C NMR (75 MHz, CDCl3): dC 21.7,
23.9, 25.2, 26.3, 47.9, 52.8, 129.4, 129.8, 130.8, 145.2, 187.9,
194.5.
2-Morpholino-1-phenyl-2-thioxo-1-ethanone (8i)
Isolated as colorless solid; 1H NMR (300 MHz, CDCl3): dH 3.61
(t, 2H, J = 5.1, CH2), 3.69 (t, 2H, J = 5.1, CH2), 3.91 (t, 2H, J = 5.1
Hz, CH2), 4.34 (t, 2H, J = 5.1 Hz, CH2), 7.51 (t, 2H, J = 8.1 Hz,
Ar–H), 7.62 (t, 1H, J = 8.1 Hz, Ar–H), 7.99 (d, 2H, J = 8.4 Hz, Ar–
H); 13C NMR (75 MHz, CDCl3): dC 47.1, 51.9, 66.3, 66.4, 128.9,
129.8, 133.2, 134.4, 187.8, 195.7.
1-(4-Methoxyphenyl)-2-piperidino-2-thioxo-1-ethanone (8c)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
1.62–1.80 (m, 6H, 3CH2), 3.53 (br s, 2H, CH2), 3.88 (s, 3H,
OCH3), 4.25 (br s, 2H, CH2), 6.95 (d, 2H, J = 8.7 Hz, Ar–H), 7.96
(d, 2H, J = 8.7 Hz, Ar–H); 13C NMR (75 MHz, CDCl3): dC 24.0,
25.3, 26.4, 48.1, 52.9, 55.6, 114.1, 126.1, 132.1, 164.4, 187.4,
194.7. Anal. calcd for C14H17NO2S: C, 63.85; H, 6.51; N, 5.32%.
Found C, 63.81; H, 6.48; N, 5.28%.
1-(4-Methylphenyl)-2-morpholino-2-thioxo-1-ethanone (8j)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.42 (s, 3H, CH3), 3.58 (t, 2H, J = 4.5 Hz,CH2), 3.67 (t, 2H, J = 4.8
Hz, CH2), 3.89 (t, 2H, J = 4.8 Hz, CH2), 4.31 (t, 2H, J = 4.5 Hz,
CH2), 7.28 (d, 2H, J = 8.1 Hz, Ar–H), 7.87 (d, 2H, J = 8.1 Hz, Ar–
H); 13C NMR (75 MHz, CDCl3): dC 21.6, 46.8, 51.6, 66.1, 66.2,
129.4, 129.7, 130.5, 145.4, 187.6, 195.6; m/z 272.17 [M + 23]
(calcd. 272.08 [M + 23]); Anal. calcd for C13H15NO2S: C, 62.62;
H, 6.06; N, 5.62%. Found C, 62.59; H, 6.02; N, 5.58%.
1-(4-Chlorophenyl)-2-piperidino-2-thioxo-1-ethanone (8d)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
1.62–1.83 (m, 6H, 3CH2), 3.53 (br s, 2H, CH2), 4.26 (br s, 2H,
CH2), 7.26 (d, 2H, J = 8.4 Hz, Ar–H), 7.98 (d, 2H, J = 8.4 Hz, Ar–
H); 13C NMR (75 MHz, CDCl3): dC 23.8, 25.4, 26.3, 48.1, 52.8,
128.9, 129.8, 133.5, 134.5, 187.6, 194.5.
1-(4-Methoxyphenyl)-2-morpholino-2-thioxo-1-ethanone (8k)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
3.61 (br s, 2H, CH2), 3.69 (br s, 2H, CH2), 3.88 (br s, 5H, CH2,
OCH3), 4.33 (t, 2H, J = 4.2 Hz, CH2), 6.96 (d, 2H, J = 8.7 Hz, Ar–
H), 7.96 (d, 2H, J = 8.7 Hz, Ar–H); 13C NMR (75 MHz, CDCl3): dC
47.1, 51.9, 55.6, 66.4, 66.5, 114.3, 126.1, 132.3, 164.6, 187.2,
196.2.
1-Phenyl-2-tetrahydro-1H-1-pyrrolyl-2-thioxo-1-ethanone (8e)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.02–2.10 (m, 4H, 2CH2), 3.55 (t, 2H, J = 6 Hz, CH2), 3.94 (t, 2H,
J = 6 Hz, CH2), 7.49 (t, 2H, J = 7.5 Hz, Ar–H), 7.59 (t, 1H, J = 7.5
Hz, Ar–H), 7.99 (d, 2H, J = 7.5 Hz, Ar–H); 13C NMR (75 MHz,
CDCl3): dC 23.7, 26.0, 51.0, 51.2, 128.7, 130.0, 132.7, 134.1,
188.7, 192.5. Anal. calcd for C12H13NOS: C, 65.72; H, 5.97; N,
6.39%. Found C, 65.68; H, 5.94; N, 6.35%.
2-Amino-4-phenyl-3-thienyl cyanide (9)
Isolated as a colorless solid; m.p. 102–105 uC; 1H NMR (300
MHz, CDCl3): dH 4.93 (s, 2H, NH2), 6.35 (s, 1H, CH), 7.35–7.44
(m, 3H, Ar–H), 7.56–7.59 (m, 2H, Ar–H); 13C NMR (75 MHz,
CDCl3): dC 88.5, 105.9, 115.8, 127.1, 128.2, 128.8, 134.1, 140.0,
163.5. Anal. calcd for C11H8N2S: C, 65.97; H, 4.03; N, 13.99%.
Found C, 65.93; H, 4.00; N, 14.04%.
1-(4-Methylphenyl)-2-tetrahydro-1H-1-pyrrolyl-2-thioxo-1-
ethanone (8f)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.02–2.11 (m, 4H, 2CH2), 2.43 (s, 3H, CH3), 3.54 (t, 2H, J = 6.3
Hz, CH2), 3.95 (t, 2H, J = 6.3 Hz, CH2), 7.28 (d, 2H, J = 8.1 Hz,
Ar–H), 7.89 (d, 2H, J = 8.1 Hz, Ar–H); 13C NMR (75 MHz,
CDCl3): dC 21.8, 23.8, 26.0, 51.0, 51.1, 129.5, 130.2, 130.3,
145.3, 188.7, 193.0. Anal. calcd for C13H15NOS: C, 66.92; H,
6.48; N, 6.00%. Found C, 66.88; H, 6.44; N, 5.97%.
Spectroscopic data for compound 11
Isolated as a colorless solid; m.p. 126–127 uC; 1H NMR (300
MHz, CDCl3): dH 1.43 (tt, 1H, J = 13.5, 3.6 Hz), 1.57–1.61 (m,
1H), 1.73–1.79 (m, 1H), 2.00–2.12 (m, 1H), 2.48 (ddd, 1H, J =
16.8, 9.9, 7.5 Hz), 2.61 (ddd, 1H, J = 16.8, 6.9, 2.1 Hz), 3.00–3.03
(m, 1H), 3.35 (dd, 1H, J = 15.9, 4.2 Hz), 3.65 (td, 1H, J = 9.6, 4.2
Hz), 3.74 (dd, 1H, J = 15.9, 9.6 Hz), 4.60 (s, 2H, NH2), 7.16 (tt,
1H, J = 6.3, 1.2 Hz), 7.24–7.41 (m, 6H), 7.49 (tt, 1H, J = 7.2, 2.4
Hz), 7.88 (dd, 2H, J = 7.2, 1.2 Hz); 13C NMR (75 MHz, CDCl3): dC
17.8, 23.9, 24.7, 39.2, 43.3, 45.1, 89.7, 116.6, 122.9, 126.4,
127.9, 128.3, 128.4 (2C), 132.7, 134.1, 137.1, 143.6, 160.5, 198.6;
m/z 409.33 [M + 23] (calcd. 409.14 [M + 23]); Anal. calcd for
1-(4-Chlorophenyl)-2-tetrahydro-1H-1-pyrrolyl-2-thioxo-1-
ethanone (8g)
Isolated as a colorless solid; 1H NMR (300 MHz, CDCl3): dH
2.06–2.11 (m, 4H, 2CH2), 3.54 (t, 2H, J = 5.7 Hz, CH2), 3.65 (t,
2H, J = 5.7 Hz, CH2), 7.45 (d, 2H, J = 8.4 Hz, Ar–H), 7.94 (d, 2H, J
= 8.4 Hz, Ar–H); 13C NMR (75 MHz, CDCl3): dC 23.7, 26.0, 51.0,
51.2, 128.6, 129.0, 131.3, 140.6, 187.1, 191.8; m/z 276.17 [M +
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C24H22N2OS: C, 74.58; H, 5.74; N, 7.25%. Found C, 74.55; H,
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Acknowledgements
The authors thank DST for funds under the IRHPA program
towards the high resolution NMR spectrometer and Prof. J.
Jeyakanthan of Alagappa University, Karaikudi, India for the
X-ray diffraction study. Financial support from UGC, New
Delhi to NP is gratefully acknowledged.
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