E
C. R. Asquith et al.
Letter
Synlett
(23) (a) Konstantinova, L. S.; Rakitin, O. A.; Rees, C. W.; Amelichev, S.
A. Mendeleev Commun. 2004, 91. (b) Konstantinova, L. S.;
Rakitin, O. A. Mendeleev Commun. 2009, 55.
(24) Konstantinova, L. S.; Lysov, K. A.; Amelichev, S. A.;
Obruchnikova, N. V.; Rakitin, O. A. Tetrahedron 2009, 65, 2178.
(25) CCDC 1517984–1517999 contain the supplementary crystallo-
graphic data for 14a,b,e–m and 14o–s. The data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
(26) Sambiagio, C.; Marsden, S. P.; Blacker, A. J.; McGowan, P. C.
Chem. Soc. Rev. 2014, Recent Ullman Coupling review: 10, 3525.
(27) Cremlyn, R. J. An Introduction to Organosulfur Chemistry; John
Wiley and Sons: Chichester, 1996.
(28) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.;
Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.;
Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;
Montgomery, J. A. Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.;
Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.;
Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.;
Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam,
J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin,
A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.;
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09,
Revision E.01,; Gaussian, Inc: Wallingford, CT, 2009.
13C NMR (100 MHz, CDCl3): = 139.6 (CAr), 136.9 (CAr), 136.1
(CAr), 131.2 (CHAr), 130.4 (CHAr), 129.7 (CHAr), 129.5 (CHAr), 128.3
(CAr), 121.2 (CHAr), 120.1 (CHAr), 120.0 (CHAr), 118.5 (CAr), 113.1
(C≡N), 108.8 (CHAr), 101.3 (CHAr), 45.7 (CH2), 12.7 (CH3).
Method B
Sodium hydride (0.5 g of a 60% dispersion in mineral oil, 12.5
mmol) was added portionwise to a solution of 2-methylindole
(1.31 g, 10.0 mmol) in dry THF (20 mL). The mixture was stirred
for 30 min, and then 2-(bromomethyl)benzonitrile (1.96 g, 10.0
mmol) was added in one portion, in addition to NaI (1.50 g, 10.0
mmol). The reaction became exothermic and was cooled in an
ice bath and after stirring for 48 h at r.t., it was concentrated in
vacuo and the residue taken up in EtOAc. The solution was
washed with water, brine, dried (MgSO4), and concentrated to
dryness in vacuo. Purification via flash column chromatography
on silica gel (hexanes/EtOAc, 1:1) to afford 2-[(2-methyl-1H-
indol-1-yl)methyl]benzonitrile (12j, 1.28 g, 5.2 mmol, 52%
yield) as colorless crystals; mp 124–125 °C. HMRS: m/z calcd for
C
17H15N2 [M + H]+: 247.1235; found: 247.1233. IR (film): max
=
3055 m (C–H), 2920 m (C–H), 2851 m (C–H), 2220 s (C≡N), 1460
m (C=C), 1396 w, 747 s, 703 s cm–1. 1H NMR (400 MHz, CDCl3):
= 7.74 (1 H, dd, J = 1.2, 7.0 Hz, CHAr), 7.62–7.59 (1 H, m, CHAr),
7.40–7.34 (2 H, m, CHAr), 7.16–7.12 (3 H, m, CHAr), 6.52 (1 H, d,
J = 6.3, CHAr), 6.41 (1 H, s, CHAr), 5.55 (2 H, s, CH2), 2.39 (3 H, s,
CH3). 13C NMR (100 MHz, CDCl3): = 141.7 (CAr), 137.0 (CAr),
136.4 (CAr), 133.5 (CHAr), 132.9 (CHAr), 128.3 (CAr), 127.8 (CHAr),
126.5 (CHAr), 121.2 (CHAr), 120.0 (CHAr), 117.1 (CAr), 110.1 (C≡N),
108.9 (CHAr), 101.2 (CHAr), 44.7(CH2), 12.6 (CH3).
Method C
Disulfur dichloride (0.4 mL, 5 mmol) was added dropwise at
–35 °C to a stirred solution of DABCO (1.12 g, 10 mmol) in chlo-
roform (25 mL) under nitrogen. The mixture was stirred at r.t.
for 1 h. 3-[(2-Methyl-1H-indol-1-yl)methyl]benzonitrile (12j,
0.239 g, 1 mmol) in chloroform (5 mL) was added, and the
mixture was stirred at r.t. for 48 h under nitrogen. Triethyl-
amine (1.4 mL, 10 mmol) was then added to the resultant
mixture at 0 °C, the mixture stirred at r.t. for 2 h, heated at
reflux for 3 h, filtered, and solvents evaporated. Purification via
flash column chromatography on silica gel (hexanes/CH2Cl2) to
afford 3-{(3-thioxo-[1,2]dithiolo[4,3-b]indol-4(3H)-yl)methyl}-
benzonitrile (14l) (0.277 g, 0.82 mmol, 82% yield) as orange
crystals; mp 190–191 °C. HMRS: m/z calcd for C17H11N2S3 [M +
H]+: 339.0079; found: 339.0077. IR (film): max = 3054 m (C–H),
2952 m (C–H), 2921 m (C–H), 2872 w (C–H), 2851 w (C–H),
2226 s (C≡N), 1472 s (C=C), 1330 s, 1258 w, 1122 w, 1060 s, 685
m cm–1. (400 MHz, CDCl3): = 7.77 (1 H, dt, J = 1.0, 8.0 Hz, CHAr),
7.46 (2 H, ddd, J = 1.0, 4.8, 5.9 Hz, CHAr), 7.40–7.32 (3 H, m,
CHAr), 7.24–7.19 (2 H, m, CHAr), 6.15 (2 H, s, CHAr). 13C NMR (100
MHz, CDCl3): = 195.9 (C=S), 146.9 (CAr), 142.2 (CAr), 149.4 (CAr),
139.0 (CAr), 131.4 (CHAr), 131.3 (CAr), 130.3 (CHAr), 129.6 (CHAr),
125.5 (CAr), 121.9 (CHAr), 121.7 (CHAr), 120.6 (CHAr), 114.3
(CHAr),113.0 (C≡N), 111.8 (CHAr), 44.0 (CH2).
(29) Schmitt, J.; Lespagnol, A. Bull. Soc. Chim. Fr. 1950, 459.
(30) General Procedures
Method A
2-Methylindole (1.31 g, 10.0 mmol) in dry DMF (15 mL) was
treated with powdered KOH (0.67 g, 12.0 mmol) and the
mixture stirred for 30 min, where upon 3-(bromomethyl)ben-
zonitrile (1.99 g, 10.0 mmol) was added in one portion. The
reaction became exothermic and was cooled in an ice bath and
after stirring for 96 h at r.t., the mixture was concentrated under
vacuum and the residue taken up in EtOAc. The solution was
washed with water, brine, dried (MgSO4), and concentrated to
dryness in vacuo. Purification via flash column chromatography
on silica gel (hexanes/EtOAc, 1:1) to afford 3-[(2-methyl-1H-
indol-1-yl)methyl]benzonitrile (12k, 1.95 g, 7.4 mmol, 74%
yield) as colorless crystals; mp 120–121 °C. HMRS: m/z calcd for
C
17H14N2 [M + H]+: 247.1235; found 247.1231. IR (film): max
=
3019 m (C–H), 2945 m (C–H), 2915 m (C–H), 2224 s (C≡N), 1552
m (C=C), 1457 m, 1426 w, 1395 w, 1136 w, 783 m 744 s, 686 m
cm–1 1H NMR (400 MHz, CDCl3): = 7.60–7.57 (1 H, m, CHAr),
.
7.54 (1 H, d, J = 8.1 Hz, CHAr), 7.38 (1 H, t, J = 7.8 Hz, CHAr), 7.28
(1 H, s, CHAr), 7.17 (1 H, dq, J = 1.0, 8.1 Hz, CHAr), 7.14–7.11 (3 H,
m, CHAr), 6.38 (1 H, s, CHAr), 5.43 (2 H, s, CH2), 2.37 (3 H, s, CH3).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E