A non-isothiocyanate route to synthesize trisubstituted thioureas of arylamines using in situ generated dithiocarbamates

Article abstract of DOI:10.1039/c2ra23257j

A novel, user-friendly, and convenient method for the synthesis of trisubstituted thioureas of arylamines is presented, for the first time, using in situ generated dithiocarbamates of secondary amines. This strategy provides an excellent opportunity to access thioureas containing primary aryl amines. A non-isothiocyanate route to obtain thioureas is the advantage of this strategy, which may provide a useful route to synthesize a variety of biologically active derivatives of thioureas.

Full text of DOI:10.1039/c2ra23257j

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A non-isothiocyanate route to synthesize trisubstituted
thioureas of arylamines using in situ generated
dithiocarbamates3
Cite this: RSC Advances, 2013, 3,
3079
Begur Vasanthkumar Varun and Kandikere Ramaiah Prabhu*
A novel, user-friendly, and convenient method for the synthesis of trisubstituted thioureas of arylamines is
Received 14th September 2012,
Accepted 12th December 2012
presented, for the first time, using in situ generated dithiocarbamates of secondary amines. This strategy
provides an excellent opportunity to access thioureas containing primary aryl amines.
A non-
DOI: 10.1039/c2ra23257j
isothiocyanate route to obtain thioureas is the advantage of this strategy, which may provide a useful
route to synthesize a variety of biologically active derivatives of thioureas.
www.rsc.org/advances
on developing a strategy to synthesize trisubstituted thioureas
of arylamines using in situ generated dithiocarbamates of
Introduction
Thioureas are a potentially useful class of molecules which are
biologically active1 and serve as precursors for a variety of
biologically active heterocyclic compounds.2 Their utility as
organocatalysts, for asymmetric transformations, has led to a
variety of synthetic protocols to accomplish a large number of
thioureas.2 Di-substituted thioureas are useful as catalysts for
asymmetric reactions through their hydrogen bonding cap-
abilities.3 Whereas, trisubstituted thioureas find their applica-
tions in medicinal chemistry as they are biologically active
compounds4 as well as precursors (especially trisubstituted
thioureas of aryl amines) for useful biologically active
molecules such as 2-aminobenzothiazole derivatives, amidines
etc.5 As trisubstituted thioureas are synthesized using iso-
thiocyanates, it is important to develop methods to access
these useful compounds by employing non-isothiocyanate
routes. In this context, even today thioureas are synthesized
using hazardous precursors such as thiophosgene and
isothiocyanates.5,6 Therefore, there are few attempts to
develop safer protocols to access thioureas.7 In this direction,
we have developed strategies to synthesize thioureas by
reacting amines with molybdenum dithiocarbamate8 or
dithiocarbamates.9 But the aryl amines were unreacted under
these conditions. Therefore, these methods9 were useful in
synthesizing alkyl substituted thioureas, but were not success-
ful for the synthesis of aryl trisubstituted thioureas. In view of
the importance of aryl substituted trisubstituted thioureas,
and continuation of our expedition in developing user-friendly
methods to access thioureas, herein we report a detailed study
secondary amines.
Results and discussion
Earlier, we have reported the synthesis of trisubstituted
thioureas by reaction of secondary amines with molybdenum
xanthate.8 Further, we reported an improved method to access
thioureas using sodium dialkyldithiocarbamates and second-
ary amines in water.9 In these methods the aryl amines were
unreacted, but it was noticed that solubility of dithiocarba-
mates and amines in water are limiting factors in obtaining
the thioureas. However the reactions with aryl amines or alkyl
amines in organic solvents resulted in the formation of a
mixture of thioureas or no reactions were observed with aryl
amines in water (Scheme 1; previous work).
Unreactivity of aromatic amines under the reaction condi-
tions may be attributed to the poor nucleophilicity and
insolubility of aromatic amines in water. Further, dithiocarba-
Department of Organic chemistry, Indian Institute of Science, Bangalore, 560 012,
Karnataka, India. E-mail: prabhu@orgchem.iisc.ernet.in; Fax: +91-80-23600529;
Tel: +91-80-22932887
Electronic supplementary information (ESI) available. See DOI: 10.1039/
3
Scheme 1 Methods to synthesise trisubstituted thioureas.
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mates being poor electrophiles makes it difficult to force the
reaction between them and aromatic amines. To overcome
this problem, it is essential to modify the counter ion of
dithiocarbamate to make it compatible with organic solvents.
However, the reaction of dithiocarbamate of aromatic amines
with secondary amines in H2O or CH3CN led to the formation
of a mixture of aromatic symmetrical thioureas and unsym-
Table 1 Screening studies
metrical thioureas (Scheme 2a, also see ESI-Scheme 1, ESI ).
3
Entry 1a (equiv.)a Solvent
T (uC) Time (h) 3aa Conversionb
Nevertheless, the reaction of 1 equiv. dithiocarbamate of 1a
with 1 equiv. of 2a in CH3CN furnished 30% of 3aa and the
formation of aromatic symmetrical thiourea was not observed
(Scheme 2b). Whereas, the reaction of 2 equiv. dithiocarba-
mate of 1a with 1 equiv. of arylamine (2a) in CH3CN furnished
80% of 3aa (Scheme 2c). Then, we thought it would be
appropriate to design an in situ method to synthesize
trisubstituted thioureas of aryl amines such as 3aa.
1
2
3
4
5
1
1
1
1.5
2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
RT
80
80
80
80
80
24
6
12
6
6
6
nd
31
67
51
.98
48c
48
6
2
7
8
2
2
Dioxane 80
EtOH
6
80
80
6
6
6
47
26
51
9
10
11
2
2
2
EtOAc
Toluene 80
H2O 80
To optimize the reaction conditions, piperidine (1a) and
3-bromoaniline (2a) were used as the secondary amine and
aromatic amine (Table 1).10 Reaction of equimolar amounts of
2a with in situ generated dithiocarbamate of 1a (using CS2 and
triethylamine) in CH3CN at room temperature did not furnish
the expected thiourea (entry 1). Whereas the reactions at
elevated temperature (80 uC) resulted in the formation of the
corresponding unsymmetrical thiourea 3aa in 31% yield (entry
2, Table 1). Extending the reaction time to 12 h resulted in
better yields (67%, entry 3, Table 1). Further extension of the
reaction time did not result in any improvements of the yield.
However, increasing the amount of amine 1a (1.5 equiv.) and
performing the reaction for 6 h was not very useful as the
product 3aa was obtained in 51% (entry 4, Table 1). The
reaction of 2 equiv. of 1a with 1 equiv. of 2a at 80 uC was
pleasing as it resulted in the formation of 3aa exclusively in
quantitative yield (entry 5, Table 1). Using K2CO3 as a base or
different solvents such as dioxane, EtOH, EtOAc, toluene or
water resulted in lower yield of the product (entries 6–11,
Table 1).10 Therefore, it was decided to use 2 equiv. of
secondary amine, 2.2 equiv. of triethylamine, and 2.4 equiv. of
CS2 and carry out the further reactions in CH3CN at 80 uC.11
The scope and limitation of the reaction was further
established by carrying out reactions of a variety of secondary
amines with substituted anilines and the results are presented
in Table 2. Halosubstituted anilines such as, 4-bromoaniline,
24
nd
a
CS2 and triethylamine are used 1.2 equiv. and 1.1 equiv. with
respect to 1a. Determined by 1H NMR. Base is K2CO3. nd = Not
detected
b
c
3-bromoaniline, 2-fluoroaniline reacted with piperidine to
yield corresponding thioureas 3aa, 3ab, and 3ac in 97%, 81%
and 69% respectively (Table 2). 3,5-Bis(trifluoromethyl)aniline
under the optimal conditions reacted well with piperidine to
furnish the corresponding thiourea 3ad in 61% yield. Alkoxy
substituted anilines such as 3-methoxyaniline, 4-methoxyani-
line, and 2-methoxyaniline reacted well with piperidine to
afford their corresponding thioureas 3ae, 3af and 3ag in
excellent yields (93%, 82%, 82%, respectively, Table 2). The
reaction of aniline with piperidine under the optimal condi-
tions resulted in the formation of 3ah in good yield (83%,
Table 2). Piperidine underwent a smooth reaction with a
variety of substituted anilines such as p-toluidine, o-toluidine,
2,6-dimethylaniline, 3,5-dimethylaniline to furnish correspond-
ing thioureas 3ai, 3aj, 3ak, and 3al in excellent yields (Table 2).
Acetyl, amide and sulfonamide substituted arylamines are good
substrates for this reaction as 1-(4-aminophenyl)ethanone,
4-aminobenzamide, 4-aminobenzenesulfonamide reacted with
piperidine to produce the corresponding thioureas 3am, 3an
and 3ao in 61%, 76% and 76% respectively (Table 2). The
versatility of this methodology to access a variety of trisub-
stituted thiourea was examined with a variety of dialkylamines
and substituted anilines. As seen in Table 2, morpholine
reacted well with a variety of aromatic amines such as aniline,
2,6-dimethylaniline, 3,5-dimethylaniline, and 2,6-diisopropyla-
niline to furnish the corresponding thioureas 3bh, 3bk, 3bl, and
3bp in good to excellent yields (Table 2). As noticed earlier with
piperidine, morpholine also reacted well with aromatic amines
containing carboxylic acid, carbonyl and nitro functionalities to
furnish the corresponding thioureas 3bm, 3bq, and 3br in 63%,
85%, and 72% respectively (Table 2). Similarly, thiomorpholine
reacted well with 3-methoxy aniline and 4-bromoaniline to
furnish corresponding thioureas 3ce and 3cb in excellent yields
Scheme 2 Reactions of aryl dithiocarbamates and dialkyl dithiocarbamates.
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Table 2 Scope of the reaction
a
b
c
Isolated yields. Heated at 80 uC for 12 h. Used 3 equiv. of secondary amine.
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(90% and 88%, Table 2). Tetrahydroisoquinoline reacted well
with amines such as 4-methoxy aniline and 4-bromoaniline
under the optimal conditions to provide the corresponding
thioureas 3de and 3db in excellent yields 91% and 85%,
Table 2). 1-Benzhydrylpiperazine reacted well with 2-methylani-
line and 4-aminobenzenesulfonamide to yield the correspond-
ing trisubstituted thioureas 3ej and 3eo in good yields (93% and
62%, Table 2). 4-Benzylpiperidine reacted well with 4-bromoani-
line and 2-methoxyaniline to furnish their corresponding
thioureas 3fb and 3fg in good yields. N,N-Diethylamine reacted
smoothly with 2,6-dimethylaniline and 4-aminobenzoic acid to
afford the corresponding thioureas 3gk and 3gq in 91% and
86% respectively. Similarly, tetrahydropyrrole reacted well with
3-bromoxyaniline to afford the corresponding thioureas 3ha in
70% (Table 2). Looking at the wide spectrum of the reactivity
presented here, this reaction appeared to be versatile as electron
withdrawing or electron donating substituents on phenyl ring
has no effect on the outcome of the reaction. Additionally, the
reaction tolerates a variety of functionality such as acid, ketone,
halide, amide, nitro, and sulfonamide. The wide scope of this
reaction is established using a number of secondary amines
such as piperidine, morpholine, thiomorpholine, substituted
piperidines, pyrrolidine etc. Apart from this, many of the
products presented in the Table 2 have features of biologically
active molecules. Therefore, this method may pave way for a
new avenue to access a wide variety of useful thioureas.
To examine the application of this methodology, the scaling
up experiments of 3-bromoaniline or 4-bromoaniline (20
mmol) with piperidine under the optimal conditions were
performed. As can be seen in the Scheme 3, these reaction
proceeded well to afford the expected thioureas 3aa and 3ab in
good yields (Scheme 3).12
Scheme 4 Possible applications of trisubstituted thioureas.
Conclusion
In summary, we have demonstrated a facile and convenient
method to access trisubstituted thioureas by reacting in situ
generated dithiocarbamate of secondary amines with aryl
amines. To the best of our knowledge, this is the first report of
the reaction of in situ generated dithiocarbamate of secondary
amines with aryl amines to accomplish trisubstituted thiour-
eas of aryl amines. One of the salient features of this method is
that it does not employ isothiocyanate. Apart from these
advantages, it has been shown that the reaction is versatile
and works with a variety of substrates.
Experimental
NMR spectra were recorded on a JEOL LA-300, BRUKER-AV400
Trisubstituted thioureas can be transformed in to ami-
dines, 2-aminobenzothiazole derivatives, guanidines and
ureas (in one step), which are useful as biologically active
molecules (Scheme 4).5 Therefore, we believe that this non-
isothiocyanate route is important in small scale (academia)
and large scale (industry) preparations as it avoids phosgene
and thiophosgene.
The formation of trisubstituted thioureas of arylamines can
be explained based on our earlier observation and reports,8,9
which is presented in Scheme 5.
spectrometer in CDCl3, Tetramethylsilane (TMS; d = 0.00 ppm)
served as internal standards for H NMR. The corresponding
1
residual non-deuterated solvent signal (CDCl3: d = 77.00 ppm)
was used as internal standards for 13C NMR. IR spectra were
measured using a JASCO FT/IR-410 spectrometer, and Perkin-
Elmer FT/IR Spectrum BX, GX. Mass spectra were measured
with Micromass Q-Tof (ESI-HRMS). Column chromatography
was conducted on Silica gel 230–400 mesh (Merck) and
preparative thin-layer chromatography was carried out using
SILICA GEL GF-254.
Scheme 3 Scaling up experiment.
Scheme 5 Tentative mechanism.
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Pale brown solid; yield 97% (290 mg); mp: 165–167 uC; (lit.13
166 uC); Rf (20% EtOAc/hexane) 0.3; IR (KBr, cm21): 3449, 3249,
2946, 2922, 2854, 1583, 1534, 1487, 1420, 1282, 1326, 1236,
Typical experimental procedure
To a well stirred solution of dialkyl amine (2 mmol) and
triethylamine (222 mg, 2.2 mmol) in CH3CN (3 mL) was added
CS2 (182 mg, 2.4 mmol) drop-wise during 5 min at 0 uC, and
the stirring was continued for 10 min at 0 uC. After allowing
the reaction mixture to warm to room temperature, the stirring
was continued for additional 10 min (to expel the excess CS2).
Then was added aryl amine (1 mmol), and the reaction mixture
was heated at 80 uC until the completion of the reaction
(monitored by TLC). The evaporation of the solvent under
vacuum, followed by the addition of 2 N HCl (5 mL) resulted in
the precipitation of brown solid, which was filtered, washed
with hexane (10 mL) and dried to furnish a pale brown solid.
For the compounds 3ej and 3eo the work up procedure is as
follows: after the completion of the reaction, the crude
material was partitioned between EtOAc (10 mL)/water (30
mL). The aqueous layer was extracted with EtOAc (10 mL 6 3),
the combined organic layer was dried over anhydrous Na2SO4,
purified on a silica gel column.
1
1009, 827, 716; H NMR (400 MHz, CDCl3): d (ppm) 7.41 (2H,
d, J = 8.2 Hz), 7.18 (1H, bs), 7.01 (2H, d, J = 8.16 Hz) (3.77 (4H,
s), 1.66 (6H, s); 13C NMR (100 MHz, CDCl3): d (ppm) 182.2,
139.3, 131.9, 124.6, 117.8, 50.65, 25.5, 24.0; HRMS (ESI) (m/z):
Calculated for C12H15N2SBr (M+Na): 321.0037, found (M+Na):
321.0039.
N-(2-Fluorophenyl)piperidine-1-carbothioamide (3ac).
Prepared as described in the general experimental procedure
and purified on a silica gel column (EtOAc/hexane 5 : 95–
10 : 90): Brown semi-solid; Yield 69% (164 mg); Rf (20% EtOAc/
hexane) 0.3; IR (KBr, cm21): 3233, 2935, 2855, 1638, 1522,
1406, 1315, 1261, 1237, 1125, 1102, 1018, 853, 756; 1H NMR
(400 MHz, CDCl3): d (ppm) 7.55–7.50 (1H, m), 7.13–7.05 (4H,
m), 3.84–3.83 (4H, m), 1.68 (6H, s); 13C NMR (100 MHz,
CDCl3): d (ppm) 181.6, 154.8 (d, 1J (CF) = 243.8 Hz), 128.0 (d, 3J
3
4
(CF) = 11.1 Hz), 125.9 (d, J (CF) = 7.7 Hz), 125.7, 123.9 (d, J
(CF) = 3.8 Hz), 115.5 (2J (CF) = 19.4 Hz); HRMS (ESI) (m/z):
Calculated for C12H15N2SF (M+H): 239.1018, found (M+H):
239.1018.
Preparation of triethylammonium dithiocarbamate of
piperidine and aniline
N-(3,5-Bis(trifluoromethyl)phenyl)piperidine-1-carbothioa-
mide (3ad). Prepared as described in the general experimental
procedure: Pale brown solid; Yield 61% (217 mg); mp: 176–178
uC (lit.14 182–184 uC); (recrystallized from EtOAc/hot hexane
1 : 20), Rf (20% EtOAc/hexane) 0.3; IR (KBr, cm21): 3442, 3141,
2936, 1540, 1379, 1280, 1238, 1188, 1129, 887; 1H NMR (400
MHz, CDCl3): d (ppm) 7.65 (2H, s), 7.59 (1H, s), 7.29 (1H, br)
3.86–3.85 (4H, m), 1.72 (6H, s); 13C NMR (100 MHz, CDCl3): d
(ppm) 181.3, 141.6, 131.9 (2J3,5 (CF) = 33.3 Hz), 123.0 (q, 1J (CF)
= 271.1 Hz), 122.6 (3J4 (CF) = 3.4 Hz) , 117.6 (3J2 (CF) = 4 Hz)
50.6, 25.5, 24.0; HRMS (ESI) (m/z): Calculated for C14H14N2SF6
(M+H): 357.0860, found (M+H): 357.0850.
Triethylammonium dithiocarbamate of piperidine. To a
well-stirred solution of piperidine (2 mmol), and triethylamine
(2 mmol) in diethyl ether (3 mL) was added CS2 (2.2 mmol)
drop-wise over 2 mins at room temperature and stirred for 10
mins. The white solid precipitated was filtered, dried and used
(yield: quantitative, 524 mg). 1H NMR (400 MHz, CDCl3): d
(ppm) 917–8.97 (1H, br, m), 4.38 (4H, m), 7.23 (1H, d, J = 8 Hz),
3.15 (6H, q, J = 7.3 Hz), 1.64 (6H, s), 1.33 (9H, t, J = 7.3 Hz); 13
C
NMR (100 MHz, CDCl3): d (ppm) 208.8, 51.6, 45.6, 25.8, 24.3,
9.04 (a small amount of disulfirum was observed as impurity)
Triethylammonium dithiocarbamate of aniline. To a well-
stirred solution of aniline (2 mmol), and triethyl amine (2
mmol) in diethyl ether (3 mL) was added CS2 (2.2 mmol) drop-
wise over 2 mins at room temperature and stirred for 1 h. The
yellow solid precipitated was filtered, dried and used (yield;
N-(3-Methoxyphenyl)piperidine-1-carbothioamide (3ae).
Prepared as described in the general experimental procedure:
The crude compound was extracted with EtOAc (10 mL 6 3)
and washed with 1N HCl (30 mL), the combined organic
fractions were evaporated under reduced pressure and then
crystalized from EtOAc/hot hexane 1 : 20 to give white solid;
Yield 93% (232 mg); mp: 88–90 uC; Rf (20% EtOAc/hexane) 0.3;
IR (KBr, cm21): 3645, 3182, 2939, 2853, 1605, 1597, 1493, 1537,
1531, 1434, 1327, 1319, 1238, 1011 ,778, 713; 1H NMR (400
MHz, DMSO-d6): d (ppm) 9.15 (1H, bs), 7.17 (1H, t, J = 8.04),
6.88–6.84 (2H, m), 6.66–6.64 (1H m), 3.85–3.84 (4H, m) 3.72
(3H, s), 1.63–1.55 (6H, m); 13C NMR (100 MHz, DMSO-d6): d
(ppm) 180.7, 159.0, 142.4, 128.6, 116.9, 110.3, 109.4, 55.0, 49.3,
25.4, 23.9; HRMS (ESI) (m/z): Calculated for C13H18N2OS
(M+Na): 273.1038, found (M+Na): 273.1038.
1
90%, 486 mg). H NMR (400 MHz, CDCl3): d (ppm) 9.36 (1H,
bs), 7.65 (2H, d, J = 9.2 Hz), 7.30 (2H, t, J = 7.8 Hz), 7.11 (1H, t, J
= 7.3 Hz), 3.21 (6H, q, J = 8.0 Hz), 1.35 (9H, t, J = 8.0 Hz); 13C
NMR (100 MHz, CDCl3): d (ppm) 214.2, 140.8, 128.1, 124.5,
123.5, 45.7, 8.7.
Characterization data
N-(3-Bromophenyl)piperidine-1-carbothioamide (3aa).
Prepared as described in the general experimental procedure;
Pale brown solid; Yield 81% (242 mg); mp: 129–131 uC
(recrystallized from EtOAc/hot hexane 1 : 20); Rf (10% EtOAc/
hexane) 0.1; IR (KBr, cm21): 3442, 3190, 2935, 2919, 2853,
1585, 1591, 1537, 1438, 1315, 1232, 772, 712. 1H NMR (400
MHz, CDCl3): d (ppm) 7.36 (1H, bs), 7.27 (1H, s), 7.23 (1H, d, J
= 8 Hz), 7.16 (1H, t, J = 7.92 Hz), 7.06 (1H, d, J = 7.92 Hz), 3.78–
3.77 (4H, m), 1.66 (6H, s); 13C NMR (100 MHz, CDCl3): d (ppm)
182.0, 141.5, 130.1, 127.5, 125.5, 122.3, 121.3, 50.8, 25.4, 24.0.
HRMS (ESI) (m/z): Calculated for C12H15BrN2S (M+Na):
321.0037, found (M+Na): 321.0036.
N-(4-Methoxyphenyl)piperidine-1-carbothioamide (3af)15
.
Prepared as shown in the general experimental procedure;
Pale yellow solid. Yield 82% (205 mg); mp: 145–148 uC; (lit.16
141–144 uC); Rf (50% EtOAc/hexane) 0.4; IR (KBr, cm21): 3444,
3201, 2935, 2853, 1627, 1528, 1425, 1320, 1242, 1035, 1010,
837, 729. 1H NMR (400 MHz, CDCl3): d (ppm) 7.15 (1H, br),
7.08 (2H, d, J = 8.8 Hz), 6.85 (2H, d, J = 8.8 Hz), 3.79–3.78 (7H,
m), 1.65 (6H s); 13C NMR (100 MHz, CDCl3): d (ppm) 182.6,
157.2, 133.2, 125.9, 114.1, 55.4, 50.3, 25.4, 24.1; HRMS (ESI)
N-(4-Bromophenyl)piperidine-1-carbothioamide (3ab).
Prepared as described in the general experimental procedure;
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(m/z): Calculated for C13H18N2OS (M+Na): 273.1038, found
(M+Na): 273.1039.
13C NMR (100 MHz, DMSO-d6): d (ppm) 180.1, 138.6, 136.2,
127.5, 126.3, 49.0, 25.5, 24.0, 18.0; HRMS (ESI) (m/z):
Calculated for C14H20N2S (M+Na): 271.1245, found (M+Na):
271.1244.
N-(3,5-Dimethylphenyl)piperidine-1-carbothioamide (3al).
Prepared as described in the general experimental procedure:
Pale brown solid; Yield 89% (220 mg); mp: 133–135 uC; Rf (20%
EtOAc/hexane) 0.4; IR (KBr, cm21): 3188, 2929, 2848, 1604,
1534, 1474, 1433, 1326,S 1233, 1126,847, 721, 603; 1H NMR
(400 MHz, CDCl3): d (ppm) 7.14 (1H, bs), 6.76 (1H, s), 6.70 (2H,
s), 3.75–3.74 (m, 4H), 2.28 (6H, s), 1.64 (6H, s); 13C NMR (100
MHz, CDCl3): 182.8, 140.2, 138.7, 126.5, 120.2, 50.9, 25.4, 24.1,
21.2; HRMS (ESI) (m/z): Calculated for C14H20N2S (M+Na):
271.1245 found (M+Na): 271.1242.
N-(2-Methoxyphenyl)piperidine-1-carbothioamide (3ag).
Prepared as shown in the general experimental procedure
and purified on a silica gel column (EtOAc/hexane 5 : 95–
10 : 90). Yellow liquid: Yield 82% (206 mg); Rf (20% EtOAc/
hexane) 0.3; IR (neat): 3398, 2936, 2853, 1601, 1522, 1399,
1
1352, 1286, 1328, 1227, 1128, 1115, 1108, 1022, 852, 746; H
NMR (400 MHz, CDCl3): d (ppm) 7.72 (1H, d, J = 7.9 Hz), 7.39
(1H, bs), 7.05 (1H, t J = 8 Hz), 6.93 (1H, t, J = 7.7 Hz), 6.87 (1H, d
J = 8.2 Hz), 3.84–3.82 (7H, m), 1.67 (6H s); 13C NMR (100 MHz,
CDCl3): d (ppm) 181.1, 149.4, 128.9, 124.1, 122.1, 120.1, 110.3,
55.5, 50.1, 25.3, 24.0. HRMS (ESI) (m/z): Calculated for
C13H18N2OS (M+Na): 273.1038, found (M+Na): 273.1036.
N-Phenylpiperidine-1-carbothioamide (3ah)17. Prepared as
described in the general experimental procedure and purified
on silica gel column (EtOAc/hexane 5 : 95-10 : 90): White
crystalline solid : Yield 83% (182 mg); mp: 98–100 uC (lit.16 99–
101 uC); Rf (20% EtOAc/hexane) 0.3; IR (KBr, cm21): 3480, 3259,
3119, 3045, 2931, 2913, 2847, 2884, 2949, 1593, 1534, 1499,
1411, 1324, 1313, 1228, 1133, 1004, 753, 691; 1H NMR (400
MHz, CDCl3): d (ppm) 7.33–7.27 (3H, m), 7.14–7.09 (3H, m),
3.77–3.75 (4H, m), 1.65 (6H, m); 13C NMR (100 MHz, CDCl3): d
(ppm) 182.5, 140.3, 129.0, 124.7, 122.7, 50.8, 25.4, 24.0; HRMS
(ESI) (m/z): Calculated for C12H16N2S (M+Na): 243.0932, found
(M+Na): 243.0933.
N-(4-Acetylphenyl)piperidine-1-carbothioamide (3am).
Prepared as described in the general experimental procedure:
Pale brown solid: Yield 81% (212 mg); mp: 157–159 uC; Rf (30%
EtOAc/hexane) 0.2; IR (KBr, cm21): 3448, 3158, 2999, 2918,
2846, 1677, 1602, 1524, 1508, 1432, 1360, 1303, 1264, 1238,
1
1176, 1133, 1004, 960, 854, 835, 747, 705, 599; H NMR (400
MHz, CDCl3): d (ppm) 7.88 (2H, d, J = 8.6 Hz), 7.65 (1H, br),
7.16 (2H, d, J = 8.5 Hz), 3.79 (4H, s) 2.56 (3H s) 1.68 (6H s); 13
C
NMR (100 MHz, CDCl3): d (ppm) 197.1, 182.0, 144.8, 132.7,
129.8, 120.8, 51.3, 26.6, 25.7, 24.2; HRMS (ESI) (m/z):
Calculated for C14H18N2SO (M+Na): 285.1038, found (M+Na):
285.1041.
N-(4-Methylphenyl)piperidine-1-carbothioamide (3ai)18
.
4-(Piperidine-1-carbothioamido)benzamide (3an). Prepared
as shown in the general experimental procedure; Pale brown
solid: Yield 76% (200 mg); mp: 188–190 uC; Rf (100% EtOAC)
0.3; IR (KBr, cm21): 3798, 3611, 3396, 3177, 2938, 2840, 1695,
1604, 1517, 1418, 1300, 1231, 1131, 1031, 844, 718, 515; 1H
NMR (400 MHz, DMSO-d6): d (ppm) 9.35 (1H, br), 7.86 (1H, br),
7.78 (2H, d, J = 8.5 Hz), 7.34 (2H, d, J = 8.5 Hz), 7.23 (1H, br),
3.87–3.86 (4H, m), 1.64–1.56 (6H m); 13C NMR (100 MHz,
DMSO-d6): d (ppm) 180.5, 167.5, 144.0, 129.1, 127.4, 123.2,
49.4, 25.5, 23.8; HRMS (ESI) (m/z): Calculated for C13H17N3OS
(M+Na): 286.0990, found (M+Na): 286.0991.
Prepared as shown in the general experimental procedure:
Pale yellow solid: Yield 90% (210 mg); 130–132 uC (lit.18 132–
133 uC) (recrystallized from EtOAc/hot hexane 1 : 20); Rf (20%
EtOAc/hexane) 0.3; IR (KBr, cm21): 3208, 2923, 2855, 2022,
1519, 1324, 1233, 818, 701; 1H NMR (400 MHz, CDCl3): d (ppm)
7.25 (1H, br), 7.10 (2H, d, J = 8 Hz), 6.99 (2H, d, J = 8.1 Hz),
3.76–3.74 (4H, m), 2.31 (3H, s), 1.64 (6H, s); 13C NMR (100
MHz, CDCl3): d (ppm) 182.5, 137.6, 134.7, 129.4, 123.3, 50.5,
25.4, 24.0, 20.8. HRMS (ESI) (m/z): Calculated for C12H16N2S
(M+Na 257.1088), found (M+Na): 257.1084.
N-(2-Methylphenyl)piperidine-1-carbothioamide (3aj).
Prepared as shown in the general experimental procedure;
Pale yellow needle like crystals; Yield 88% (205 mg); mp: 97–99
uC (lit.13 98 uC) (recrystallized from EtOAc/hot hexane 1 : 20);
Rf (20% EtOAc/hexane) 0.5; IR (KBr, cm21): 3219, 2949, 2936,
1524, 1409, 1332, 1324, 1253, 1235, 1005, 762, 722; 1H NMR
(400 MHz, CDCl3): d (ppm) 7.20–7.15 (2H, m), 7.12–7.05 (2H,
m), 6.90 (1H, bs), 3.74–3.73 (4H, m), 2.25 (3H, s), 1.63–1.61
(6H, m); 13C NMR (100 MHz, CDCl3): d (ppm) 182.9, 138.8,
132.3, 130.7, 126.5, 125.9, 124.9, 50.6, 25.34, 24.0, 17.9. HRMS
(ESI) (m/z): Calculated for C13H18N2S (M+Na): 257.1088, found
(M+Na): 257.1089.
N-(4-Sulfamoylphenyl)piperidine-1-carbothioamide (3ao).
Prepared as described in the general experimental procedure;
Pale brown solid: Yield 76% (227 mg); mp: 196–199 uC; Rf (50%
EtOAc/hexane) 0.2; IR (KBr, cm21): 3796, 3721, 3557, 3333,
3244, 3158, 2932, 2849, 2244, 1598, 1531, 1428, 1285, 1242,
1302, 1156, 1133, 1009, 897, 729, 541; 1H NMR (400 MHz,
DMSO-d6): d (ppm) 9.44 (1H, br), 7.70 (2H, d, J = 8.5 Hz), 7.44
(2H, d, J = 8.5 Hz), 3.87 (4H, s), 1.64–1.57 (6H, m); 13C NMR
(100 MHz, DMSO): d (ppm) 180.4, 144.5, 138.5, 125.7, 123.6,
49.5, 25.5, 23.8; HRMS (ESI) (m/z): Calculated for
C
12H17N3O2S2 (M+Na): 322.0660, found (M+Na): 322.0662.
N-Phenylmorpholine-4-carbothioamide (3bh)19. Prepared as
N-(2,6-Dimethylphenyl)piperidine-1-carbothioamide (3ak).
Prepared as described in the general experimental procedure:
The brown solid was dissolved in 0.5 mL of DMSO, followed by
the addition of cold water (20 mL) furnished white precipitate,
which was filtered and dried. Yield 95% (235 mg); mp: 159–161
uC; Rf (20% EtOAc/hexane) 0.3; IR (KBr, cm21): 3448, 3231,
2938, 2855, 1638, 1518, 1330,1320, 1243, 1225, 1131, 1007, 854,
described in the general experimental procedure and purified
on silica gel column (EtOAc/hexane 5 : 95–10 : 90); White
solid: Yield 79% (175 mg); mp: 132–134 uC; (lit.19 136–137); Rf
(20% EtOAc/hexane) 0.1; IR (KBr, cm21): 3196, 2935, 2875,
1612, 1533, 1446, 1324, 1219, 1115, 1002, 845, 715. 1H NMR
(400 MHz, CDCl3): d (ppm) 7.47 (1H, bs), 7.35–7.31 (2H, m),
7.18–7.12 (3H, m), 3.80–3.78 (4H, m), 3.72–3.69 (4H, m); 13C
NMR (100 MHz, CDCl3): d (ppm) 183.5, 139.8, 129.1, 125.3,
1
781; H NMR (400 MHz, DMSO-d6): d (ppm) 8.77 (1H, broad),
7.05 (3H, s), 3.91–3.89 (4H, m), 2.14 (6H, s) 1.67–1.55 (6H, m);
3084 | RSC Adv., 2013, 3, 3079–3087
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123.1, 66.0, 49.5; HRMS (ESI) (m/z): Calculated for C11H14N2OS
(M+H): 223.0905, found (M+H): 223.0906.
65.8, 48.8; HRMS (ESI) (m/z): Calculated for C12H14N2O3S
(M+H): 267.0803, found (M+H) 267.0808.
N-(2,6-Dimethylphenyl)morpholine-4-carbothioamide (3bk).
Prepared as described in the general experimental procedure;
Pale brown solid; Yield 94% (235 mg); mp: 138–140 uC; Rf (30%
EtOAc/hexane) 0.3; IR (KBr, cm21): 3210, 2923, 2860, 1671,
1517, 1399, 1339, 1275, 1235, 1119, 1029, 942, 781; 1H NMR
(400 MHz, DMSO-d6): d (ppm) 8.95 (1H, bs), 7.07 (3H, s), 3.92–
3.90 (4H, m), 3.66–3.64 (4H, m), 2.14 (6H, s); 13C NMR (100
MHz, DMSO-d6): d (ppm) 181.3, 138.2, 136.1, 127.6, 126.5,
65.9, 48.2, 17.9 HRMS (ESI) (m/z): Calculated for C13H18N2OS
(M+Na): 273.1038, found (M+Na): 273.1035.
N-(3,5-Dimethylphenyl)morpholine-4-carbothioamide
(3bl)20. Prepared as described in the general experimental
procedure; White solid; Yield 88% (220 mg); mp: 155–157u;
(lit.20 153–154 uC); Rf (20% EtOAc/hexane) 0.3; IR (KBr, cm21):
3451, 3216, 2966, 2854, 2917, 1612, 1542, 1535, 1332, 1230,
1212, 1115, 1025, 843, 722; 1H NMR (400 MHz, CDCl3): d (ppm)
7.27 (1H, broad), 6.80 (1H, s), 6.72 (2H, s), 3.80–3.78 (4H, m),
3.72–3.71 (4H, m), 2.3 (6H, s); 13C NMR (100 MHz, CDCl3): d
(ppm) 183.8, 139.6, 139.0, 127.1, 120.4, 66.1, 49.8, 21.3 HRMS
(ESI) (m/z): Calculated for C13H18N2OS (M+Na): 273.1038,
found (M+Na): 273.1037.
N-(2,6-Diisopropylphenyl)morpholine-4-carbothioamide
(3bp). Prepared as described in the general experimental
procedure; pale yellow solid; Yield 72% (220 mg); mp: 175–177
uC; Rf (20% EtOAc/hexane) 0.2; IR (KBr, cm21): 3271, 2926,
2962, 2865, 1513, 1302, 1339, 1322, 1273, 1229, 1120, 1028,
802, 678. 1H NMR (400 MHz, DMSO-d6): d (ppm) 8.83 (1H, bs),
7.23 (1H, t, J = 7.46), 7.13 (2H, t, J = 7.36 Hz), 3.94 (4H, s), 3.66
(4H, s), 3.02–3.2.95 (2H, m), 1.44 (6H, d, J = 6.64 Hz), 1.13 (6H,
d, J = 6.6 Hz); 13C NMR (100 MHz, DMSO-d6): d (ppm) 182.7,
146.2, 135.6, 127.3, 122.9, 65.9, 48.4, 27.9, 23.4, 23.2. HRMS
(ESI) (m/z): Calculated for C17H26N2OS (M+Na): 329.1664,
found (M+Na): 329.1660.
N-(4-Acetylphenyl)morpholine-4-carbothioamide (3bm).
Prepared as described in the general experimental procedure;
Pale yellow solid: Yield 63% (166 mg); mp: 87–89 uC; Rf (50%
EtOAc/hexane) 0.1; IR (KBr, cm21): 3448, 3151, 3091, 2977,
2894, 2856, 1682, 1672, 1603, 1587, 1525, 1421, 1358, 1316,
1302, 1219, 1178, 1066, 1028, 861, 834, 742, 589; 1H NMR (400
MHz, CDCl3); d (ppm) 7.90 (2H, d, J = 8.5 Hz), 7.75 (1H, br),
7.22 (2H, d, J = 8.5 Hz), 3.87–3.85 (4H, m), 3.76–3.74 (4H, m),
2.56 (3H s); 13C NMR (100 MHz, CDCl3): d (ppm) 197.0, 182.8,
144.1, 133.0, 129.5, 121.3, 66.0, 49.8, 26.4; HRMS (ESI) (m/z):
Calculated for C13H16N2O2S (M+Na): 287.0830, found (M+Na):
287.0841.
N-(3-Nitrophenyl)morpholine-4-carbothioamide (3br).
Prepared as described in the general experimental procedure;
pale brown solid; Yield 73% (195 mg); mp: 200–202 uC; (the
crude compound was recrystallized from EtOAc/hexane 1 : 20).
Rf (50% EtOAc/hexane) 0.25; IR (KBr, cm21): 3440, 3149, 2982,
2849, 1589, 1560, 1524, 1474, 1347, 1314, 1301, 1229, 1119,
1030, 811, 723; 1H NMR (400 MHz, DMSO-d6): d (ppm) 9.7 (1H,
br), 8.27 (1H, s), 7.93 (1H, d, J = 8.12 Hz), 7.81 (1H, d, J = 8 Hz),
7.57 (1H, t, J = 8 Hz), 3.92–3.91 (4H, m), 3.66 (4H, m); 13C NMR
(100 MHz, DMSO-d6): d (ppm) 180.7, 146.8, 141.8, 130.3, 128.6,
118.3, 118.0, 65.2, 48.1. HRMS (ESI) (m/z): Calculated for
C11H13N3O3S (M+Na): 290.0575, found (M+ Na): 290.0579.
N-(4-Bromophenyl)thiomorpholine-4-carbothioamide (3cb).
Prepared as described in the general experimental procedure
and purified on silica gel column (EtOAc/hexane 5 : 95–
10 : 90); White crystalline solid: Yield 86% (273 mg); mp:
188–190 uC (lit.21 189.5–190.5 uC); Rf (20% EtOAc/hexane) 0.3;
IR (KBr, cm21): 3436, 3179, 3150, 3084, 3003, 2909, 1586, 1525,
1486, 1423, 1308, 1290, 1186, 1164, 957, 823, 729; 1H NMR (400
MHz, DMSO-d6): d (ppm) 9.35 (1H, bs), 7.46 (2H, d, J = 8.6 Hz),
7.23 (2H, d, J = 8.6 Hz), 4.17 (4H, s), 2.67 (4H, s); 13C NMR (100
MHz, DMSO-d6): d (ppm) 180.7, 140.0, 130.5, 127.4, 116.5,
50.7, 26.0; HRMS (ESI) (m/z): Calculated for C16H15N2SBr
(M+Na): C11H13N2S2Br (M+Na): 338.9601, found (M+Na):
338.9602.
N-(3-Methoxyphenyl)thiomorpholine-4-carbothioamide
(3ce). Prepared as shown in the general experimental
procedure and purified on silica gel column (EtOAc/hexane
5 : 95–10 : 90); White solid; Yield 90% (241 mg); mp: 126–128
uC; Rf (20% EtOAc/hexane) 0.5; IR (KBr, cm21): 3443.9, 3193,
2915, 1598, 1528, 1490, 1417, 1336, 1231, 1155, 1181, 1043,
1
967, 952, 861, 782, 710; H NMR (400 MHz, CDCl3): d (ppm)
7.36 (1H, br), 7.22 (1H, t, J = 8.4 Hz), 6.70–6.65 (3H, m), 4.08–
4.06 (4H, m), 3.79 (3H, s), 2.71–2.68 (4H, m); 13C NMR (100
MHz, CDCl3): d (ppm) 183.6, 160.2, 141.0, 129.9, 114.8, 110.5,
108.6, 55.3, 52.5, 26.9. HRMS (ESI) (m/z): Calculated for
C12H16N2OS2 (M+Na): 291.0602, found (M+Na): 291.0605.
N-(4-Bromophenyl)-3,4-dihydroisoquinoline-2(1H)-car-
bothioamide (3db). Prepared as described in the general
experimental procedure and purified on silica gel column
(EtOAc/hexane 5 : 95–10 : 90); White solid: Yield 85% (298
mg); mp: 168–170 uC; Rf (20% EtOAc/hexane) 0.5; IR (KBr,
cm21): 3448, 3200, 3031, 2967, 2906, 1584, 1528, 1489, 1451,
1425, 1316, 1305, 1211, 1176, 748, 722; 1H NMR (400 MHz,
CDCl3): d (ppm) 7.40 (2H, d, J = 8.6 Hz), 7.26–7.18 (4H, m),
7.12–7.10 (3H, m), 4.92 (2H, s) 3.98 (2H, t, J = 5.8 Hz), 2.96 (2H,
t, J = 5.8 Hz); 13C NMR (100 MHz, CDCl3): d (ppm) 181.8, 138.8,
134.7, 132.4, 131.8, 127.9, 127.3, 126.8, 126.4, 126.2, 118.6,
50.7, 46.9, 28.6. HRMS (ESI) (m/z): Calculated for C16H15N2SBr
(M+Na): 369.0037, found (M+Na): 369.0039.
4-(Morpholine-4-carbothioamido)benzoic acid (3bq).
Prepared as described in the general experimental procedure;
pale brown solid: Yield 85% (226 mg); mp: 193–195 uC; (the
crude compound was recrystallized from EtOAc/hexane 1 : 15).
Rf (5% MeOH/DCM) 0.2; IR (KBr, cm21): 3427, 3152, 2963,
2865, 2534, 1702, 1609, 1522, 1420, 1291, 1265, 124, 1170,
1120, 1029, 864, 771, 722; 1H NMR (400 MHz, DMSO-d6): d
(ppm) 12.71 (1H, br), 9.58 (1H, br), 7.86 (2H, d, J = 8 Hz), 7.45
(2H, d, J = 8 Hz), 3.89 (4H, s), 3.65 (4H, s); 13C NMR (100 MHz,
DMSO-d6): d (ppm) 181.3, 167.0, 145.3, 129.5, 125.5, 123.2,
N-(3-Methoxyphenyl)-3,4-dihydroisoquinoline-2(1H)-car-
bothioamide (3de). Prepared as described in the general
experimental procedure and purified on silica gel column
(EtOAc/hexane 5 : 95–10 : 90); White solid: Yield 91% (271
mg); mp: 104–106 uC; Rf (20% EtOAc/hexane) 0.2; IR (KBr,
cm21): 3271, 2923, 2852, 1605, 1557, 1525, 1494, 1455, 1435,
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1318, 1198, 1043, 1018, 749, 707; 1H NMR (400 MHz, CDCl3): d
(ppm) 7.29 (1H, bs), 7.26–7.16 (4H, m), 7.11–7.09 (1H, m),
6.79–6.70 (2H, m), 6.68 (1H, d , J = 1.76), 4.89 (2H, s), 3.99 (2H,
t, J = 5.8), 3.75 (3H s), 2.96 (2H, t, J = 5.8 Hz); 13C NMR (100
MHz, CDCl3): d (ppm) 182.4, 160.0, 141.0, 134.7, 132.6, 129.6,
128.0, 127.1, 126.6, 126.3, 115.9, 110.9, 109.6, 55.3, 51.1, 47.3,
28.6; HRMS (ESI) (m/z): Calculated for C17H18N2OS (M+Na):
321.1038, found (M+Na): 321.1036.
Hz), 7.39 (1H, br), 7.30–7.25 (2H, m), 7.19 (1H , t, J = 7.1 Hz),
7.13 (2H, d, J = 7.4 Hz), 7.04 (1H, t, J = 78 Hz), 6.92 (1H, t, J = 7.7
Hz), 6.86 (1H, d, J = 8.2 Hz), 4.61 (2H, d, J = 13.2 Hz), 3.83 (3H,
s), 3.03–2.97 (2H, m), 2.56 (2H, d, J = 7.2 Hz), 1.87–1.79 (1H,
m), 1.71 (2H, d, J = 13.3 Hz), 1.41–1.31 (2H, m); 13C NMR (100
MHz, CDCl3): d (ppm) 181.4, 149.4, 139.7, 129.0, 128.9, 128.2,
126.0, 124.3, 122.1, 120.3, 110.4, 55.6, 49.5, 42.6, 37.9, 31.6;
HRMS (ESI) (m/z): Calculated for
C20H24N2OS (M+Na):
363.1507, found (M+Na): 363.1506.
4-Benzhydryl-N-(o-tolyl)piperazine-1-carbothioamide (3ej).
Prepared as described in the general experimental procedure
and purified on silica gel column (EtOAc/hexane 5 : 95–
10 : 90); White solid: Yield 93% (372 mg); mp: 216–218 uC; Rf
(20% EtOAc/hexane) 0.5; purified on silica gel. IR (KBr, cm21):
3449, 3219, 3024, 2812, 1582, 1451, 1519, 1399, 1333, 1231,
1145, 1028, 997, 722, 704; 1H NMR (400 MHz, CDCl3): d (ppm)
7.39 (4H, d, J = 7.4 Hz), 7.28–7.24 (4H, m), 7.19–7.14 (4H, m),
7.09 (1H ,d, J = 7.36 Hz), 7.06–704 (1H, m), 6.91 (1H, br), 4.22
(1H, s), 3.76–3.74 (4H, m), 2.41 (4H, t, J = 5.0 Hz), 2.2 (3H, s);
13C NMR (100 MHz, CDCl3): d (ppm) 183.7, 141.9, 138.7, 131.9,
130.9, 128.6, 127.8, 127.2, 126.7, 126.0, 124.6, 75.7, 51.2, 49.6,
17.9; HRMS (ESI) (m/z): Calculated for C25H27N3S (M +H):
402.2004, found (M+H): 402.2006.
4-Benzhydryl-N-(4-sulfamoylphenyl)piperazine-1-carbothioa-
mide (3eo). Prepared as described in the general experimental
procedure and purified on silica gel column (EtOAc/hexane
5 : 95–10 : 90); White solid: Yield 62% (289 mg); mp: 210–212;
Rf (50% EtOAc/hexane) 0.4; IR (KBr, cm21): 3794, 3387, 3136,
2896, 2801, 2349, 1760, 1529, 1431, 1327, 1300, 1239, 1225,
1161, 1150, 1006, 923, 747, 708; 1H NMR (400 MHz, DMSO-d6):
d (ppm) 9.51 (1H, br), 7.71 (2H, d, J = 8.4 Hz), 7.46–7.44 (6H,
m), 7.31 (4H, t, J = 7.4 Hz), 7.23 (2H, br), 7.21 (2H, t, J = 7.08
Hz), 4.40 (1H, s), 3.92 (4H, s), 2.39 (4H, s); 13C NMR (100 MHz,
DMSO-d6): d (ppm) 190.0, 144.2, 142.3, 138.8, 128.6, 127.7,
127.0, 125.7, 123.8, 74.4, 51.2, 48.2; HRMS (ESI) (m/z):
Calculated for C24H26N4O2S2 (M+Na): 489.1395, found
(M+Na): 489.1392.
3-(2,6-Dimethylphenyl)-1,1-diethylthiourea (3gk). Prepared
as described in the general experimental procedure: pale
brown solid. Yield 91% (215 mg); mp: 124–126 uC (the crude
black solid obtained by filtration was dissolved in 1 mL of
DMSO followed by the addition of cold water (20 mL) resulted
in the pale brown solid precipitate). Rf (20% EtOAc/hexane)
0.3; IR (KBr, cm21): 3195, 2923, 1514, 1257, 905. H NMR (400
1
MHz, CDCl3) 7.14–7.04 (3H, m), 6.58 (1H, br), 3.77 (4H, q, J =
6.8 Hz), 2.24 (6H, s), 1.31 (6H, t, J = 7.1 Hz); 13C NMR (100
MHz, CDCl3): d (ppm) 180.2, 137.1, 136.6, 128.1, 127.4, 45.4,
18.43, 12.8; HRMS (ESI) (m/z): Calculated for C13H20N2S
(M+Na) 259.1245, found (M+Na): 259.1249.
4-(3,3-Diethylthioureido)benzoic acid (3gq). Prepared as
described in the general experimental procedure: pale brown
solid; Yield 86% (216 mg); 155–157 uC; (the crude compound
was recrystallized from EtOAc/hexane 1 : 15), Rf (20% EtOAc/
hexane) 0.07; Yield 86%; mp: 135–138; Rf (5% MeOH/CH2Cl2)
0.05; IR (KBr, cm21): 3197, 2979, 2934, 2906, 2543, 1702, 1609,
1523, 1422, 1319, 1281, 1244, 1171, 1137, 905, 792, 723; 1H
NMR (400 MHz, DMSO-d6) 12.69 (1H, br), 9.08 (1H, s), 7.85
(2H, d, J = 8.4 Hz), 7.46 (2H, d, J = 8.5 Hz), 3.77 (4H, q, J = 6.9
Hz), 1.17 (6H, t, J = 6.9 Hz); 13C NMR (100 MHz, DMSO-d6): d
(ppm) 179.4, 167.1, 145.4, 129.1, 125.9, 124.8, 45.04, 12.7;
HRMS (ESI) (m/z): Calculated for C12H16N2O2S (M+Na):
275.0830, found (M+Na): 275.0834.
N-(3-Bromophenyl)pyrrolidine-1-carbothioamide (3ha).
Prepared as described in the general experimental procedure
and purified on silica gel column (EtOAc/hexane 10 : 90–
20 : 80); White solid; Yield 70% (200 mg); 155–157 uC; Rf (20%
EtOAc/hexane) 0.07; IR (KBr, cm21): 3255, 2968, 1719, 1526,
1436, 1342, 1298, 864, 701. 1H NMR (400 MHz, DMSO-d6) 8.94
(1H, br), 7.66 (1H, s), 7.41 (1H, d, J = 7.4 Hz), 7.79–7.22 (2H, m),
3.61 (4H, br), 1.92 (4H, br); 13C NMR (100 MHz, DMSO-d6): d
(ppm) 177.2, 142.3, 129.8, 127.8, 126.8, 124.3, 120.4, 48.7, 24.7.
4-Benzyl-N-(4-bromophenyl)piperidine-1-carbothioamide
(3fb). Prepared as described in the general experimental
procedure and purified on silica gel column (EtOAc/hexane
5 : 95–10 : 90); White solid: Yield 86% (334 mg); mp: 174–176
uC; Rf (20% EtOAc/hexane) 0.3; IR (KBr, cm21): 3754, 3438,
3200, 2939, 2913, 2872, 2847, 1523, 1321, 1277, 1212, 747, 716,
1
702; H NMR (400 MHz, CDCl3): d (ppm) 7.40 (2H, d, J = 8.4
HRMS (ESI) (m/z): Calculated for
C11H13N2SBr (M+Na):
Hz), 7.30–7.26 (2H, m), 7.22–7.18 (2H, m), 7.13 (2H, d, J = 7.4
Hz), 7.00 (2H, d, J = 8.4 Hz), 4.54 (2H, d, J = 12.8 Hz), 2.93 (2H,
t, J = 12.2 Hz), 2.56 (2H, d, J = 7.08 Hz), 1.84–1.79 (1H m), 1.70
(2H, d, J = 13.1 Hz), 1.37–1.25 (2H, m); 13C NMR (100 MHz,
CDCl3): d (ppm) 182.1, 139.6, 139.2, 131.9, 129.0, 128.3, 126.1,
124.7, 117.9, 49.9, 42.5, 37.8, 31.6; HRMS (ESI) (m/z):
Calculated for C19H21BrN2S (M+Na): 411.0507, found (M+Na):
411.0506.
4-Benzyl-N-(2-methoxyphenyl)piperidine-1-carbothioamide
(3fg). Prepared as described in the general experimental
procedure and purified on silica gel column (EtOAc/hexane
5 : 95–10 : 90); yellow liquid: Yield —81% (275 mg); Rf (20%
EtOAc/hexane) 0.4; IR (neat): 3501, 3208, 2926, 2656, 2255,
1994, 1910, 1618, 1600, 1495, 1411, 1320, 1227, 1194, 1022,
769, 751; 1H NMR (400 MHz, CDCl3): d (ppm) 7.71 (1H, d, J = 8
306.9881, found (M+Na): 306.9881.
Acknowledgements
The financial assistant from CSIR (No. 01/2415/10-EMR-II) is
acknowledged with thanks. Thanks are due to Dr A. R.
Ramesha and Prof. S. Chandrasekhar for useful suggestions.
BVV thanks CSIR for a fellowship.
Notes and references
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