Synthesis of 2,N,N-trisubstituted 1H-indole-1-carbothioamides from 2-(acylmethyl)phenyl isocyanides

Article abstract of DOI:10.1002/hlca.201200236

A convenient procedure for the synthesis of 2,N,N-trisubstituted 1H-indole-1-carbothioamides from 2-(acylmethyl)phenyl isocyanides has been developed. Thus, these isocyanides are converted into (Z)- [1-alkyl (or phenyl)-2-(2-isothiocyanatophenyl)ethenyl] 1,1-dimethylethyl carbonates via an easy two-step sequence. Treatment with secondary amines gave thiourea intermediates which afforded with CF₃COOH (TFA) the desired products in fair-to-good yields. Copyright

Full text of DOI:10.1002/hlca.201200236

Helvetica Chimica Acta – Vol. 96 (2013)
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Synthesis of 2,N,N-Trisubstituted 1H-Indole-1-carbothioamides from
2-(Acylmethyl)phenyl Isocyanides
by Kazuhiro Kobayashi*, Kazuya Yamane, and Shuhei Fukamachi
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of
Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
(phone/fax: þ 81(857)315263; e-mail: kkoba@chem.tottori-u.ac.jp)
A convenient procedure for the synthesis of 2,N,N-trisubstituted 1H-indole-1-carbothioamides from
2-(acylmethyl)phenyl isocyanides has been developed. Thus, these isocyanides are converted into (Z)-
[1-alkyl (or phenyl)-2-(2-isothiocyanatophenyl)ethenyl] 1,1-dimethylethyl carbonates via an easy two-
step sequence. Treatment with secondary amines gave thiourea intermediates which afforded with
CF3COOH (TFA) the desired products in fair-to-good yields.
Introduction. – Undoubtedly, 1H-indole is one of the most important heterocycles.
Therefore, a large numbers of synthetic studies on the synthesis of 1H-indole
derivatives have been reported [1]. However, few general methods have been reported
for the synthesis of 1H-indole-1-carbothioamide derivatives [2][3], whilst some reports
on the biological activity of these 1H-indole derivatives have been published [3]. On
the other hand, we recently reported a convenient method to prepare 3,N,N-
trisubstituted 1H-indole-1-carbothioamides utilizing the HI-mediated cyclization
reaction of the corresponding thiourea intermediates, generated in situ from a-
substituted 2-isothiocyanatophenyl-b-methoxystyrenes and secondary amines [4].
Now, we would like to disclose a facile method for the synthesis of 2,N,N-trisubstituted
1H-indole-1-carbothioamides. Our method is based on CF3COOH (TFA)-mediated
cyclization of the thiourea derivatives 4, derived from (Z)-[1-alkyl(or phenyl)-2-(2-
isothiocyanatophenyl)ethenyl] 1,1-dimethylethyl carbonates 3 and secondary amines.
It should be noted that, after completion of our work, we became aware of the report by
Kaname and Sashida, who described the formation of 2,N,N-trisubstituted 1H-indole-
1-carbothioamides along with 2-imino-4-methylidene-1H-1,3-benzothiazines by silver
trifluoromethanesulfonate (AgOTf)-promoted cyclization of the N-(2-ethynylphen-
yl)thioureas, derived from 2-ethynylphenyl isothiocyanates and secondary amines [5].
Results and Discussion – The procedure outlined in Scheme 1 illustrates our
synthesis of 2,N,N-trisubstituted 1H-indole-1-carbothioamides 5 from 2-(acylmethyl)-
phenyl isocyanides 1. Treatment of 1 with di(tert-butyl) dicarbonate ((Boc)2O) in
pyridine afforded (Z)-2-[1-alkyl(or phenyl)-2-(2-isocyanophenyl)ethenyl] 1,1-dime-
thylethyl carbonates 2. First, this conversion was conducted at 808 for several hours, and
the yields of 2 were low-to-moderate. Subsequently, the reaction proved to proceed
smoothly even at room temperature by using a catalytic amount of 4-(dimethylami-
no)pyridine (DMAP) to provide fair-to-good yields of 2. The transformation of 2 into
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 96 (2013)
Scheme
the corresponding isothiocyanates 3 on treatment with S8 in the presence of a catalytic
amount of Se was successfully achieved in good yields according to the procedure of
Fujiwara et al. [6].
The conversion of carbonates 3 to the desired products 5 could be conducted as a
one-pot reaction. Thus, secondary amines were added to the solutions of 3 in CH2Cl2 at
room temperature, and the attack of the amines on the isothiocyanate C-atom of 3 was
complete immediately to give the corresponding thiourea derivatives 4. After removal
of CH2Cl2 under reduced pressure, TFA was added. TFA-Mediated cyclization of 4
proceeded smoothly at room temperature to provide 5. The results compiled in the
Table indicate that generally good yields of 5 were obtained. However, when the
substrate 3 with R3 ¼ Ph (i.e., 3c and 3d) was used, the yields of the products 5g – 5i were
somewhat lower (Entries 7 – 9) than those of 3 with R3 ¼ Me or Et.
Table. Preparation of 2,N,N-Trisubstituted 1H-Indole-2-carbothioamides 5
Entry
3
R4R5NH
5
Yielda) [%]
1
2
3
4
5
6
7
8
9
3a (R1 ¼ R2 ¼ H, R3 ¼ Me)
Pyrrolidine
Morpholine
Et2NH
Piperidine
Et2NH
MeNHPh
Pyrrolidine
Piperidine
Pyrrolidine
Pyrrolidine
5a
5b
5c
5d
5e
5f
5g
5h
5i
86
84
85
90
85
77
66
64
55
84
3a
3a
3b (R1 ¼ R2 ¼ H, R3 ¼ Et)
3b
3b
3c (R1 ¼ R2 ¼ H, R3 ¼ Ph)
3c
3d (R1 ¼ H, R2 ¼ Me, R3 ¼ Ph)
10
3e (R1 ¼ OMe, R2 ¼ H, R3 ¼ Et)
5j
a) Yields of isolated products.

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In conclusion, the developed procedure provides a convenient access to 2,N,N-
trisubstituted 1H-indole-1-carbothioamides, which are difficult to prepare by previous
methods. Since the method is operationally simple, and the starting materials are
readily available, it may be of value in organic synthesis.
Experimental Part
General. All of the org. solvents used in this study were dried over appropriate drying agents and
distilled prior to use. TLC: Merck silica gel 60 PF254. Column chromatography (CC): Wako Gel C-200E.
M.p.: Laboratory Devices MEL-TEMP II melting point apparatus; uncorrected. IR Spectra:
PerkinꢀElmer Spectrum65 FTIR spectrophotometer. 1H-NMR Spectra: in CDCl3 with TMS as an
internal reference with Bruker Biospin AVANCE II 600 spectrometer, at 600 MHz, JEOL ECP500 FT
NMR spectrometer, at 500 MHz, or a JEOL LA400 FT NMR spectrometer, at 400 MHz. 13C-NMR
Spectra: in CDCl3 with TMS as an internal reference with Bruker Biospin AVANCE II 600, at 150 MHz,
JEOL ECP500 FT NMR spectrometer, at 125 MHz, or a JEOL LA400FT NMR spectrometer, 100 MHz.
LR-MS (EI, 70 eV): with JEOL JMS AX505 HA spectrometer. HR-MS (DART, pos.-ion mode):
Thermo Scientific Exactive spectrometer.
2-Methylphenyl isocyanides were prepared as described in [7]. BuLi was supplied by Asia Lithium
Corporation. All other chemicals used in this study were commercially available.
(2-Isocyanophenyl)methyl ketones 1 were prepared from 2-methylphenyl isocyanides as described in
[8]. The physical, spectroscopic, and anal. data for new compounds are given below.
1-(2-Isocyanophenyl)butan-2-one (1b). Yield: 0.88 g (51%). Pale-yellow liquid. Rf (AcOEt/hexane
1
1:5) 0.46. IR (neat): 2121, 1722, 1623. H-NMR (400 MHz): 1.12 (t, J ¼ 7.4, 3 H); 2.60 (q, J ¼ 7.4, 2 H);
3.88 (s, 2 H); 7.26 (d, J ¼ 7.8, 1 H); 7.31 (dd, J ¼ 7.8, 6.9, 1 H); 7.36 (d, J ¼ 7.8, 1 H); 7.39 (dd, J ¼ 7.8, 6.9,
1 H). HR-MS: 174.0915 ([M þ H]þ, C11H12NOþ; calc. 174.0919).
2-(2-Isocyano-4-methylphenyl)-1-phenylethanone (1d). Yield: 0.74 g (63%). Yellow solid. M.p. 108 –
1108 (hexane/Et2O). IR (KBr): 2127, 1686. 1H-NMR (400 MHz): 2.36 (s, 3 H); 4.42 (s, 2 H); 7.19 (s, 2 H);
7.25 (s, 1 H); 7.50 (dd, J ¼ 7.8, 7.3, 2 H); 7.60 (t, J ¼ 7.3, 1 H); 8.04 (d, J ¼ 7.8, 2 H). Anal. calc. for C16H13NO
(235.28): C 81.68, H 5.57, N 5.95; found: C 81.50, H 5.59, N 5.91.
1-(2-Isocyano-5-methoxyphenyl)butan-2-one (1e). Pale-yellow liquid. Rf (AcOEt/hexane 1:5) 0.41.
IR (neat): 2119, 1722, 1606. 1H-NMR (400 MHz): 1.11 (t, J ¼ 7.4, 3 H); 2.59 (q, J ¼ 7.4, 2 H); 3.81 (s, 3 H);
3.83 (s, 2 H); 6.75 (d, J ¼ 2.9, 1 H); 6.79 (dd, J ¼ 8.8, 2.9, 1 H); 7.32 (d, J ¼ 8.8, 1 H). HR-MS: 204.1044
([M þ H]þ, C12H14NOþ2 ; calc. 204.1025).
tert-Butyl (1Z)-1-(2-Isocyanophenyl)prop-1-en-2-yl Carbonate (2a). General Procedure. A soln. of
1a (0.44 g, 2.8 mmol) and (Boc)2O (0.60 g, 2.8 mmol) in pyridine (1 ml) containing DMAP (0.10 g,
0.83 mmol) was stirred at r.t. until disappearance of 1a (TLC (SiO2; AcOEt/hexane 1:2; ca. 15 min)).
H2O (15 ml) was added, and the mixture was extracted with AcOEt (3 ꢁ 10 ml). The combined extracts
were washed with sat. aq. NH4Cl (4 ꢁ 10 ml) and brine (10 ml), and dried (Na2SO4). Evaporation of the
solvent gave a residue, which was purified by CC (SiO2) to give 2a (0.43 g, 60%). Pale-yellow oil. Rf
(CHCl3/hexane 1:1) 0.43. IR (neat): 2119, 1756, 1676. 1H-NMR (500 MHz): 1.46 (s, 9 H); 2.18 (d, J ¼ 1.1,
3 H); 6.19 (br. s, 1 H); 7.24 (ddd, J ¼ 8.0, 7.4, 1.1, 1 H); 7.35 (ddd, J ¼ 8.0, 7.4, 1.1, 1 H); 7.36 (d, J ¼ 8.0,
1 H); 7.69 (d, J ¼ 8.0, 1 H). Anal. calc. for C15H17NO3 (259.30): C 69.48, H 6.61, N 5.40; found: C 69.40, H
6.65, N 5.47.
tert-Butyl (1Z)-1-(2-Isocyanophenyl)but-1-en-2-yl Carbonate (2b). Yellow oil. Rf (AcOEt/hexane
1:10) 0.43. IR (neat): 2119, 1757, 1675. 1H-NMR (500 MHz): 1.21 (t, J ¼ 7.4, 3 H); 1.42 (s, 9 H); 2.48 (q,
J ¼ 7.4, 2 H); 6.19 (s, 1 H); 7.22 (t, J ¼ 7.4, 1 H); 7.32 – 7.37 (m, 2 H); 7.68 (d, J ¼ 7.4, 1 H). Anal. calc. for
C16H19NO3 (273.33): C 70.31, H 7.01, N 5.12; found: C 70.36, H 7.07, N 4.95.
tert-Butyl (Z)-2-(2-Isocyanophenyl)-1-phenylethenyl Carbonate (2c). Pale-yellow solid. M.p. 74 –
1
768 (hexane/Et2O). IR (KBr): 2119, 1762, 1647. H-NMR (600 MHz): 1.40 (s, 9 H); 6.89 (s, 1 H); 7.28
(td, J ¼ 7.7, 1.4, 1 H); 7.40 – 7.44 (m, 5 H); 7.63 (dd, J ¼ 7.9, 1.4, 2 H); 7.90 (d, J ¼ 8.0, 1 H). Anal. calc. for
C20H19NO3 (321.37): C 74.75, H 5.96, N 4.36; found: C 74.74, H 5.99, N 4.06.

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Helvetica Chimica Acta – Vol. 96 (2013)
tert-Butyl (Z)-2-(2-Isocyano-4-methylphenyl)-1-phenylethenyl Carbonate (2d). Pale-yellow solid.
M.p. 110 – 1128 (hexane/Et2O). IR (KBr): 2117, 1762, 1650. 1H-NMR (500 MHz): 1.40 (s, 9 H); 2.36 (s,
3 H); 6.85 (s, 1 H); 7.21 – 7.23 (m, 2 H); 7.37 – 7.43 (m, 3 H); 7.62 (dd, J ¼ 8.0, 1.7, 2 H); 7.79 (d, J ¼ 8.6,
1 H). Anal. calc. for C21H21NO3 (335.40): C 75.20, H 6.31, N 4.18; found: C 75.26, H 6.44, N 4.09.
tert-Butyl (1Z)-1-(2-Isocyano-5-methoxyphenyl)but-1-en-2-yl Carbonate (2e). Pale-yellow oil. Rf
(AcOEt/hexane 1:5) 0.56. IR (neat): 2117, 1759, 1674, 1603. 1H-NMR (500 MHz): 1.21 (t, J ¼ 7.4, 3 H);
1.42 (s, 9 H); 2.48 (qd, J ¼ 7.4, 1.1, 2 H); 3.81 (s, 3 H); 6.17 (s, 1 H); 6.74 (dd, J ¼ 8.6, 2.2, 1 H); 7.24 (d, J ¼
2.9, 1 H); 7.28 (d, J ¼ 8.6, 1 H). Anal. calc. for C17H21NO4 (303.35): C 67.31, H 6.98, N 4.62; found: C 67.28,
H 7.08, N 4.51.
tert-Butyl (1Z)-1-(2-isothiocyanatophenyl)alk-1-en-2-yl] carbonates 3 were prepared by treating 2
with S8 in the presence of Se under conditions reported in [6].
tert-Butyl (1Z)-1-(2-isothiocyanatophenyl)prop-1-en-2-yl carbonate (3a). Pale-yellow oil. Rf
(AcOEt/hexane 1:40) 0.29. IR (neat): 2101, 1755, 1678. 1H-NMR (500 MHz): 1.44 (s, 9 H); 2.16 (d,
J ¼ 1.1, 3 H); 6.11 (s, 1 H); 7.18 – 7.23 (m, 3 H); 7.58 (dd, J ¼ 8.0, 2.3, 1 H). Anal. calc. for C15H17NO3S
(291.37): C 61.83, H 5.88, N 4.81; found: C 61.82, H 5.93, N 4.73.
tert-Butyl (1Z)-1-(2-Isothiocyanatophenyl)but-1-en-2-yl Carbonate (3b). Pale-yellow oil. Rf
(AcOEt/hexane 1:30) 0.34. IR (neat): 2078, 1756, 1674. 1H-NMR (500 MHz): 1.21 (t, J ¼ 7.4, 3 H);
1.41 (s, 9 H); 2.46 (q, J ¼ 7.4, 2 H); 6.13 (s, 1 H); 7.19 – 7.21 (m, 3 H); 7.57 (dd, J ¼ 8.0, 1.7, 1 H). Anal. calc.
for C16H19NO3S (305.39): C 62.93, H 6.27, N 4.59; found: C 62.80, H 6.36, N 4.59.
tert-Butyl (Z)-2-(2-Isothiocyanatophenyl)-1-phenylethenyl Carbonate (3c). Pale-yellow oil. Rf
1
(THF/hexane 1:4) 0.53. IR (neat): 2081, 1762, 1646. H-NMR (600 MHz): 1.39 (s, 9 H); 6.83 (s, 1 H);
7.25 – 7.30 (m, 3 H); 7.38 (tt, J ¼ 7.3, 0.9, 1 H); 7.42 (dd, J ¼ 7.8, 7.3, 2 H); 7.64 (dd, J ¼ 7.8, 0.9, 2 H); 7.81
(dd, J ¼ 7.5, 2.0, 1 H). Anal. calc. for C20H19NO3S (353.43): C 67.97, H 5.42, N 3.96; found: C 67.80, H 5.27,
N 3.92.
tert-Butyl (Z)-2-(2-Isothiocyanato-4-methylphenyl)-1-phenylethenyl Carbonate (3d). Pale-yellow
solid. M.p. 114 – 1168 (hexane/Et2O). IR (KBr): 2114, 1755, 1650. 1H-NMR (500 MHz): 1.40 (s, 9 H); 2.34
(s, 3 H); 6.80 (s, 1 H); 7.09 (d, J ¼ 8.0, 1 H); 7.10 (s, 1 H); 7.36 (t, J ¼ 7.4, 1 H); 7.42 (t, J ¼ 7.4, 2 H); 7.62 (d,
J ¼ 7.4, 2 H); 7.70 (d, J ¼ 8.0, 1 H). Anal. calc. for C21H21NO3S (367.46): C 68.64, H 5.76, N 3.81; found: C
68.46, H 5.83, N 3.70.
tert-Butyl (1Z)-1-(2-Isothiocyanato-5-methoxyphenyl)but-1-en-2-yl Carbonate (3e). Pale-yellow oil.
1
Rf (AcOEt/hexane 1:40) 0.39. IR (neat): 2088, 1756, 1674, 1600. H-NMR (400 MHz): 1.21 (t, J ¼ 7.3,
3 H); 1.42 (s, 9 H); 2.46 (q, J ¼ 7.3, 2 H); 3.79 (s, 3 H); 6.10 (s, 1 H); 6.73 (dd, J ¼ 8.8, 2.9, 1 H); 7.13 (d, J ¼
8.8, 1 H); 7.16 (d, J ¼ 2.9, 1 H). Anal. calc. for C17H21NO4S (335.42): C 60.87, H 6.31, N 4.18; found: C
60.87, H 6.34, N 4.10.
(2-Methyl-1H-indol-1-yl)(pyrrolidin-1-yl)methanethione (5a). General Procedure. To a stirred soln.
of 3a (0.27 g, 0.81 mmol) in CH2Cl2 (1 ml) at r.t. was added pyrrolidine (58 mg, 0.81 mmol). After
confirmation of complete consumption of 3a (TLC (SiO2; THF/hexane 1:5; within 5 min)), the solvent
was removed under reduced pressure. Then, the residual thiourea precursor was dissolved in TFA (1 ml),
and the soln. was stirred at r.t. until TLC analyses (SiO2; AcOEt/hexane 1:2) indicated that the thiourea
precursor had disappeared (ca. 10 min). Sat. aq. NaHCO3 (20 ml) was added, and the mixture was
extracted with CH2Cl2 (3 ꢁ 10 ml). The combined extracts were washed with sat. aq. NaHCO3 (10 ml)
and H2O (10 ml), and dried (Na2SO4). After evaporation of the solvent, the residue was purified by prep.
TLC (SiO2) to give 5a (0.20 g, 86%). Pale-yellow oil. Rf (AcOEt/hexane 1:2) 0.66. IR (neat) 1488, 1451,
1205. 1H-NMR (400 MHz): 1.92 – 1.98 (m, 2 H); 2.10 – 2.13 (m, 2 H); 2.46 (s, 3 H); 3.20 – 3.24 (m, 1 H);
3.27 – 3.31 (m, 1 H); 4.00 – 4.04 (m, 2 H); 6.34 (s, 1 H); 7.10 (ddd, J ¼ 8.0, 7.3, 2.3, 1 H); 7.13 – 7.18 (m,
2 H); 7.49 (d, J ¼ 7.4, 1 H). 13C-NMR (125 MHz): 13.2; 24.8; 25.9; 51.5; 53.5; 103.5; 110.1; 120.0; 120.8;
122.0; 128.5; 134.8 (two overlapped Cs); 178.4. HR-MS: 245.1096 ([M þ H]þ, C14H17N2Sþ; calc.
245.1112). Anal. calc. for C14H16N2S (244.36): C 68.81, H 6.60, N 11.46; found: C 68.94, H 6.68, N 11.52.
(2-Methyl-1H-indol-1-yl)(morpholin-4-yl)methanethione (5b). Pale-yellow solid. M.p. 66 – 728
(hexane/Et2O). IR (KBr): 1483, 1455, 1236. 1H-NMR (500 MHz): 2.46 (s, 3 H); 3.27 (br. s, 2 H);
3.54 – 3.58 (m, 2 H); 3.94 – 3.96 (m, 2 H); 4.39 – 4.42 (m, 2 H); 6.37 (s, 1 H); 7.13 (ddd, J ¼ 7.4, 6.9, 1.1,
1 H); 7.18 (ddd, J ¼ 8.0, 6.9, 1.1, 1 H); 7.24 (d, J ¼ 8.0, 1 H); 7.49 (d, J ¼ 7.4, 1 H). 13C-NMR (125 MHz):
13.3; 50.5; 50.8; 66.3; 66.6; 104.3; 110.2; 120.1; 121.3; 122.4; 128.5; 135.5; 135.7; 180.9. HR-MS: 261.1066

Helvetica Chimica Acta – Vol. 96 (2013)
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([M þ H]þ, C14H17N2OSþ; calc. 261.1061). Anal. calc. for C14H16N2OS (260.35): C 64.58, H 6.19, N 10.76;
found: C 64.50, H 6.33, N 10.66.
N,N-Diethyl-2-methyl-1H-indole-1-carbothioamide (5c). Pale-yellow oil. Rf (AcOEt/hexane 1:5)
0.56. IR (neat): 1501, 1456, 1214. 1H-NMR (500 MHz): 1.08 (t, J ¼ 7.4, 3 H); 1.51 (t, J ¼ 7.4, 3 H); 2.46 (s,
3 H); 3.22 – 3.29 (m, 1 H); 3.35 – 3.42 (m, 1 H); 4.10 – 4.17 (m, 1 H); 4.23 – 4.29 (m, 1 H); 6.37 (s, 1 H);
7.10 – 7.20 (m, 3 H); 7.51 (d, J ¼ 8.0, 1 H). 13C-NMR (125 MHz): 11.2; 13.0; 13.9; 46.7; 47.5; 103.5; 110.0;
119.9; 120.8; 122.1; 128.5; 135.3; 135.9; 181.0. HR-MS: 247.1263 ([M þ H]þ, C14H19N2Sþ; calc. 247.1269).
Anal. calc. for C14H18N2S (246.37): C 68.25, H 7.36, N 11.37; found: C 68.20, H 7.48, N 11.36.
(2-Ethyl-1H-indol-1-yl)(piperidin-1-yl)methanethione (5d). Pale-yellow oil. Rf (AcOEt/hexane
1:10) 0.40. IR (neat): 1489, 1454, 1240. 1H-NMR (500 MHz): 1.33 (t, J ¼ 7.4, 3 H); 1.43 – 1.53 (m,
2 H); 1.70 – 1.75 (m, 2 H); 1.89 – 1.91 (m, 2 H); 2.73 – 2.80 (m, 1 H); 2.91 – 2.99 (m, 1 H); 2.99 – 3.27 (m,
2 H); 4.29 – 4.38 (m, 2 H); 6.38 (s, 1 H); 7.11 (dd, J ¼ 8.0, 6.9, 1 H); 7.16 (dd, J ¼ 8.0, 6.9, 1 H); 7.20 (d, J ¼
8.0, 1 H); 7.51 (d, J ¼ 8.0, 1 H). 13C-NMR (125 MHz): 12.7; 20.4; 24.0; 25.3; 26.9; 51.4; 51.6; 101.9; 110.2;
120.0; 120.9; 122.1; 128.3; 135.7; 141.9; 180.1. HR-MS: 273.1415 ([M þ H]þ, C16H21N2Sþ; calc. 273.1425).
Anal. calc. for C16H20N2S (272.41): C 70.55, H 7.40, N 10.28; found: C 70.53, H 7.48, N 10.07.
2,N,N-Triethyl-1H-indole-1-carbothioamide (5e). Pale-yellow oil. Rf (AcOEt/hexane 1:10) 0.39. IR
(neat): 1500, 1455, 1211. 1H-NMR (500 MHz): 1.05 (t, J ¼ 7.4, 3 H); 1.35 (t, J ¼ 7.4, 3 H); 1.49 (t, J ¼ 7.4,
3 H); 2.61 – 2.69 (m, 1 H); 2.91 – 2.99 (m, 1 H); 3.19 – 3.26 (m, 1 H); 3.28 – 3.35 (m, 1 H); 4.10 – 4.24 (m,
2 H); 6.38 (s, 1 H); 7.09 – 7.17 (m, 3 H); 7.51 (d, J ¼ 7.4, 1 H). 13C-NMR (125 MHz): 11.1; 12.3; 13.9; 20.2;
46.7; 47.3; 101.5; 109.9; 120.1; 120.8; 122.1; 128.4; 135.8; 141.6; 181.1. HR-MS. 261.1435 ([M þ H]þ,
C15H21N2Sþ; calc. 261.1425). Anal. calc. for C15H20N2S (260.40): C 69.19, H 7.74, N 10.76; found: C 69.12,
H 7.89, N 10.61.
2-Ethyl-N-methyl-N-phenyl-1H-indole-1-carbothioamide (5f). Pale-yellow solid. M.p. 98 – 998 (hex-
ane/CH2Cl2). IR (KBr): 1492, 1454, 1194. 1H-NMR (500 MHz): 1.28 (t, J ¼ 7.4, 3 H); 2.59 – 2.67 (m, 1 H);
2.89 – 2.97 (m, 1 H); 3.95 (s, 3 H); 6.13 (s, 1 H); 6.96 – 7.34 (m, 8 H); 7.46 (d, J ¼ 8.0, 1 H). 13C-NMR
(125 MHz): 12.4; 20.7; 39.3; 102.2; 104.0; 111.0; 119.8; 120.8; 121.9; 123.7; 127.4; 128.4; 128.9; 134.9; 141.7;
179.7. HR-MS: 295.1261 ([M þ H]þ, C18H19N2Sþ; calc. 295.1269). Anal. calc. for C18H18N2S (294.41): C
73.43, H 6.16, N 9.51; found: C 73.44, H 6.37, N 9.40.
(2-Phenyl-1H-indol-1-yl)(pyrrolidin-1-yl)methanethione (5g). Pale-yellow solid. M.p. 172 – 1738
(hexane/CH2Cl2). IR (KBr): 1603, 1488, 1450, 1209. 1H-NMR (600 MHz): 1.61 – 1.77 (m, 3 H); 1.94 – 1.99
(m, 1 H); 2.96 – 2.98 (m, 2 H); 3.71 – 3.76 (m, 1 H); 3.92 – 3.97 (m, 1 H); 6.75 (s, 1 H); 7.19 (td, J ¼ 7.9, 0.9,
1 H); 7.27 (ddd, J ¼ 8.2, 7.9, 0.9, 1 H); 7.35 (tt, J ¼ 7.4, 1.2, 1 H); 7.40 (dd, J ¼ 7.8, 7.4, 2 H); 7.61 (d, J ¼ 7.9,
1 H); 7.69 (dd, J ¼ 8.2, 0.9, 2 H); 7.75 (dd, J ¼ 8.2, 0.9, 1 H). 13C-NMR (150 MHz): 24.4; 25.7; 51.6; 53.4;
104.7; 112.0; 120.6; 121.6; 123.3; 127.3; 128.1; 128.7; 128.8; 132.2; 136.6; 138.5; 178.0. HR-MS: 307.1265
([M þ H]þ, C19H19N2Sþ; calc. 307.1269). Anal. calc. for C19H18N2S (306.42): C 74.47, H 5.92, N 9.14;
found: C 74.47, H 5.82, N 9.05.
(2-Phenyl-1H-indol-1-yl)(piperidin-1-yl)methanethione (5h). Colorless crystals. M.p. 106 – 1078
1
(hexane/Et2O). IR (KBr): 1604, 1488, 1452, 1247. H-NMR (500 MHz): 0.99 – 1.02 (m, 1 H); 1.21 –
1.27 (m, 1 H); 1.40 – 1.43 (m, 1 H); 1.54 – 1.57 (m, 2 H); 1.74 – 1.80 (m, 1 H); 2.77 – 2.82 (m, 1 H);
3.00 – 3.06 (m, 1 H); 3.82 – 3.87 (m, 1 H); 4.29 – 4.33 (m, 1 H); 6.73 (s, 1 H); 7.19 (d, J ¼ 8.0, 7.4, 1 H); 7.26
(dd, J ¼ 8.0, 7.4, 1 H); 7.35 (t, J ¼ 7.4, 1 H); 7.42 (t, J ¼ 7.4, 2 H); 7.60 (d, J ¼ 8.0, 1 H); 7.68 (d, J ¼ 7.4, 2 H);
7.75 (d, J ¼ 8.0, 1 H). 13C-NMR (150 MHz): 23.8; 24.9; 26.1; 51.1; 51.6; 104.6; 112.2; 120.6; 121.6; 123.3;
127.8; 128.1; 128.5; 128.7; 131.9; 137.5; 139.1; 179.9. HR-MS: 321.1414 ([M þ H]þ, C20H21N2Sþ; calc.
321.1425). Anal. calc. for C20H20N2S (320.45): C 74.96, H 6.29, N 8.74; found: C 74.81, H 6.30, N 8.64.
(6-Methyl-2-phenyl-1H-indol-1-yl)(pyrrolidin-1-yl)methanethione (5i). Pale-yellow solid. M.p. 80 –
1
848 (hexane/Et2O). IR (KBr): 1603, 1494, 1447, 1261. H-NMR (500 MHz): 1.56 – 1.75 (m, 3 H); 1.95 –
1.97 (m, 1 H); 2.48 (s, 3 H); 2.94 – 2.97 (m, 2 H); 3.70 – 3.75 (m, 1 H); 3.92 – 3.97 (m, 1 H); 6.69 (s,
1 H); 7.01 (d, J ¼ 8.0, 1 H); 7.32 (t, J ¼ 7.4, 1 H); 7.40 (dd, J ¼ 8.0, 7.4, 2 H); 7.48 (d, J ¼ 8.0, 1 H); 7.55 (s,
1 H); 7.67 (d, J ¼ 8.0, 2 H). 13C-NMR (150 MHz): 22.0; 24.4; 25.7; 51.5; 53.4; 104.5; 112.0; 120.2; 123.3;
126.6; 127.2; 127.8; 128.6; 132.4; 133.3; 137.0; 137.9; 178.2. HR-MS: 321.1416 ([M þ H]þ, C20H21N2Sþ; calc.
321.1425). Anal. calc. for C20H20N2S (320.45): C 74.96, H 6.29, N 8.74; found: C 74.90, H 6.45, N 8.65.
(2-Ethyl-5-methoxy-1H-indol-1-yl)(pyrrolidin-1-yl)methanethione (5j). Pale-yellow oil. Rf (AcOEt/
hexane 1:4) 0.40. IR (neat): 1616, 1476, 1448, 1205. 1H-NMR (500 MHz): 1.30 (t, J ¼ 7.4, 3 H); 1.91 – 1.97

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Helvetica Chimica Acta – Vol. 96 (2013)
(m, 2 H); 2.04 – 2.14 (m, 2 H); 2.74 – 2.81 (m, 1 H); 2.90 – 2.98 (m, 1 H); 3.20 – 3.25 (m, 1 H); 3.28 – 3.24
(m, 1 H); 3.83 (s, 3 H); 3.96 – 4.05 (m, 2 H); 6.30 (s, 1 H); 6.80 (dd, J ¼ 9.2, 2.3, 1 H); 7.00 (d, J ¼ 2.3, 1 H);
7.02 (d, J ¼ 9.2, 1 H). 13C-NMR (100 MHz): 12.7; 20.6; 24.8; 25.9; 51.5; 53.5; 55.9; 101.8; 102.7; 110.7;
111.5; 129.0; 130.0; 142.0; 154.9; 178.7. HR-MS: 289.1373 ([M þ H]þ, C16H21N2OSþ; calc. 289.1374).
Anal. calc. for C16H20N2OS (288.41): C 66.63, H 6.99, N 9.71; found: C 66.52, H 6.87, N, 9.67.
This work was supported in part by a Grant-in-Aid for Scientific Research (C) 22550035 from Japan
Society for the Promotion of Science. Assistance in recording mass spectra and performing combustion
analyses by Mrs. Miyuki Tanmatsu of our university is gratefully acknowledged.
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Received May 8, 2012