10.1002/ejoc.201900503
European Journal of Organic Chemistry
FULL PAPER
NH2), 7.98 (s, 1H, ArH), 12.73 (bs, 1H, NH). 13C NMR (101 MHz,
DMSO-d6) δ 13.6, 116.0, 138.1, 151.2, 155.2, 163.7. HRMS calcd for
C6H8N5S, 182.0500; found, 182.0504.
1H NMR (400 MHz, CDCl3) δ 2.13 (s, 6H, SCH3), 4.99 (s, 1H, CH), 7.54
(ddd, J = 8.1, 6.9, 1.2 Hz, 1H, ArH), 7.70 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H,
ArH), 7.81 (ddd, J = 8.2, 1.7, 0.8 Hz, 1H, ArH), 8.09 (dd, J = 8.5, 0.9
Hz, 1H, ArH), 8.15 (d, J = 2.2 Hz, 1H, ArH), 8.96 (d, J = 2.3 Hz, 1H,
ArH). 13C NMR (101 MHz, CDCl3) δ 14.9, 54.1, 127.1, 127.5, 127.9,
129.3, 129.7, 132.6, 133.9, 147.7, 150.8. HRMS calcd for C12H14NS2,
236.0568; found, 236.0564.
2-(methylthio)benzo[d]thiazole (2m):60 white solid (79.6 mg, 88 %).
1H NMR (400 MHz, CDCl3) δ 2.78 (s, 3H, SCH3), 7.27 (ddd, J = 8.0, 7.3,
1.2 Hz, 1H, ArH), 7.41 (ddd, J = 8.3, 7.3, 1.3 Hz, 1H, ArH), 7.74 (ddd,
J = 7.9, 1.3, 0.6 Hz, 1H, ArH), 7.88 (ddd, J = 8.2, 1.2, 0.6 Hz, 1H, ArH).
13C NMR (101 MHz, CDCl3) δ 16.0, 121.0, 121.4, 124.1, 126.1, 135.2,
153.4, 168.1.
Supporting Information
1
6-chloropyridin-3-amine (6a):61 light brown solid (19 mg, 30 %) H
NMR (400 MHz, CDCl3) δ 3.67 (bs, 2H, NH2), 6.95 (dd, J = 8.5, 3.0 Hz,
1H, ArH), 7.07 (d, J = 8.5 Hz, 1H, ArH), 7.84 (d, J = 3.0 Hz, 1H, ArH).
13C NMR (101 MHz, CDCl3) δ 124.3, 125.0, 136.4, 140.3, 141.8.
Addtional experimental details and copies of 1H and 13C NMR
spectra for all products are provided in the supporting information.
6-chloro-2-(methylthio)pyridin-3-amine (7a):62 light brown solid
(30 mg, 35%) 1H NMR (400 MHz, CDCl3) δ 2.61 (s, 3H, SCH3) 3.63
(bs, 2H, NH2), 6.81 (d, J = 8.1 Hz, 1H, ArH), 6.86 (d, J = 8.1 Hz, 1H,
ArH). 13C NMR (101 MHz, CDCl3) δ 13.5, 120.0, 122.9, 139.0, 139.8,
144.5. HRMS calcd for C6H8N2SCl, 175.0097; found, 175.0104.
Acknowledgments
The authors would like to thank Dr Mohammadreza Shariatgorji
and Dr. Anna Nilsson (Uppsala University) as well as Dr. Lisa
Haigh (Imperial College London, U.K.) for assistance with accu-
rate mass determination. The research was supported by Upp-
sala University and the Swedish Research Council (Veten-
skapsrådet 2018-05133).
1
2-chloropyridin-3-amine (6b):63 tan solid (32.5 mg, 51 %) H NMR
(400 MHz, CDCl3) δ 4.06 (bs, 2H, NH2), 7.06–7.01 (m, 2H, ArH), 7.82–
7.75 (m, 1H, ArH). 13C NMR (101 MHz, CDCl3) δ 122.6, 123.5, 137.0,
138.6, 139.8.
2-chloro-6-(methylthio)pyridin-3-amine (7b): light brown solid,
m.p. 55-57 °C (18.5 mg, 21 %). 1H NMR (400 MHz, DMSO-d6) δ 2.42
(s, 3H, SCH3), 5.39 (br s, 2H, NH2), 7.04 (d, J = 8.2 Hz, 1H, ArH), 7.10
(d, J = 8.2 Hz, 1H, ArH). 13C NMR (101 MHz, DMSO-d6) δ 13.7, 121.7,
123.9, 134.3, 138.4, 143.4. HRMS Calcd for C6H8N2SCl, 175.0097;
found, 175.0099.
Keywords: heterocycles • thiomethylation • reduction • nucleo-
philic substitution •
[1]
[2]
M. Feng, B. Tang, S. H. Liang, X. Jiang. Curr. Top. Med. Chem. 2016,
16, 1200–1216.
S. Montanari, C. Paradisi, G. Scorrano. J. Org. Chem. 1991, 56,
4274–4279.
3-aminopyridine (6c):64 light brown solid (25.6 mg, 54 %). 1H NMR
(400 MHz, CDCl3) δ 3.67 (bs, 2H, NH2), 6.95 (ddd, J = 8.2, 2.8, 1.4 Hz,
1H, ArH), 7.05 (ddd, J = 8.2, 4.7, 0.8 Hz, 1H, ArH), 7.99 (dd, J = 4.7,
1.4 Hz, 1H, ArH), 8.08 (dd, J = 2.9, 0.8 Hz, 1H, ArH). 13C NMR (101
MHz, CDCl3) δ 121.6, 123.8, 137.5, 140.0, 142.7.
[3]
[4]
Y.-J. Cherng. Tetrahedron. 2002, 58, 4931–4935.
L.-K. Huang, Y.-C. Cherng, Y.-R. Cheng, J.-P. Jang, Y.-L. Chao, Y.-
J. Cherng. Tetrahedron. 2007, 63, 5323–5327.
D. Sieb, K. Schuhen, M. Morgen, H. Herrmann, H. Wadepohl, N. T.
Lucas, R. W. Baker, M. Enders. Organometallics. 2012, 31, 356–364.
A. K. Pathak, V. Pathak, L. E. Seitz, W. J. Suling, R. C. Reynolds.
Bioorg. Med. Chem. 2013, 21, 1685–1695.
[5]
[6]
[7]
K. Čapková, Y. Yoneda, T. J. Dickerson, K. D. Janda. Bioorg. Med.
Chem. Lett. 2007, 17, 6463–6466.
N. W. Johnson, M. Semones, J. L. Adams, M. Hansbury, J. Winkler.
Bioorg. Med. Chem. Lett. 2007, 17, 5514–5517.
L. Testaferri, M. Tiecco, M. Tingoli, D. Bartoli, A. Massoli.
Tetrahedron. 1985, 41, 1373–1384.
E. Jones-Mensah, J. Magolan. Tetrahedron Lett. 2014, 55, 5323–
5326.
C. E. Hoyle, A. B. Lowe, C. N. Bowman. Chem. Soc. Rev. 2010, 39,
1355–1387.
W. Zhao, P. Xie, Z. Bian, A. Zhou, H. Ge, M. Zhang, Y. Ding, L. Zheng.
J. Org. Chem. 2015, 80, 9167–9175.
Q. Qiao, R. Dominique, A. Sidduri, J. Lou, R. A. Goodnow. Synth.
Commun. 2010, 40, 3691–3698.
J. Heidebrecht, C. Gendy, B. S. Gelfand, R. Roesler. Polyhedron.
2018, 143, 138–143.
J. M. Serrano-Becerra, H. Valdés, D. Canseco-González, V. Gómez-
Benítez, S. Hernández-Ortega, D. Morales-Morales. Tetrahedron
Lett. 2018, 59, 3377–3380.
V. Gómez-Benítez, H. Valdés, S. Hernández-Ortega, J. Manuel
German-Acacio, D. Morales-Morales. Polyhedron. 2018, 143, 144–
148.
V. Gómez-Benítez, O. Baldovino-Pantaleón, C. Herrera-Álvarez, R.
A. Toscano, D. Morales-Morales. Tetrahedron Lett. 2006, 47, 5059–
5062.
N. Taniguchi. J. Org. Chem. 2004, 69, 6904-6906.
O. Baldovino-Pantaleón, S. Hernández-Ortega, D. Morales-Morales.
Adv. Synth. Catal. 2006, 348, 236–242.
5-chloropyridin-2-amine (6d):65 white solid (46.2 mg, 72 %). 1H
NMR (400 MHz, CDCl3) δ 4.50 (bs, 2H, NH2), 6.44 (d, J = 8.7, 0.7 Hz,
1H, ArH), 7.36 (dd, J = 8.7, 2.6 Hz, 1H, ArH), 7.99 (d, J = 2.5 Hz, 1H,
ArH). 13C NMR (101 MHz, CDCl3) δ 109.6, 121.0, 137.7, 146.4, 156.9.
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
1
2-aminopyridine (6e):66 white solid (21.1 mg, 47 %). H NMR (400
MHz, CDCl3) δ 4.39 (bs, 2H, NH2), 6.50 (dd, J = 8.3, 0.9 Hz, 1H, ArH),
6.63 (ddd, J = 7.2, 5.1, 1.0 Hz, 1H, ArH), 7.42 (ddd, J = 8.3, 7.2, 1.9
Hz, 1H, ArH), 8.05 (ddd, J = 5.1, 1.9, 0.9 Hz, 1H, ArH). 13C NMR (101
MHz, CDCl3) δ 108.9, 114.1, 138.0, 147.9, 158.4.
1
6-chloropyridin-2(1H)-one (8a):67 white solid (52.5 mg, 79 %). H
NMR (400 MHz, CDCl3) δ 6.68 (dd, J = 8.5, 0.8 Hz, 1H, ArH), 6.73 (dd,
J = 7.5, 0.8 Hz, 1H, ArH), 7.54 (dd, J = 8.5, 7.5 Hz, 1H, ArH), 12.04 (bs,
1H, NH). 13C NMR (101 MHz, CDCl3) δ 111.8, 113.5, 142.4, 144.2,
165.1. HRMS calcd for C5H5NOCl, 130.0060; found, 130.0059.
[16]
[17]
nicotinic acid (8b):68 white solid (41.5 mg, 67 %). 1H NMR (400 MHz,
DMSO-d6) δ 7.52 (ddd, J = 7.9, 4.9, 0.9 Hz, 1H, ArH), 8.25 (dd, J = 7.9,
2.0 Hz, 1H, ArH), 8.77 (dd, J = 4.9, 1.8 Hz, 1H, ArH), 9.07 (dd, J = 2.2,
0.9 Hz, 1H, ArH). 13C NMR (101 MHz, DMSO-d6) δ 123.8, 126.8,
137.0, 150.3, 153.3, 166.4.
[18]
[19]
[20]
O. Baldovino-Pantaleón, S. Hernández-Ortega, D. Morales-Morales.
Inorg. Chem. Commun. 2005, 8, 955–959.
3-(bis(methylthio)methyl)quinoline (8c): yellow oil (48 mg, 41 %).
This article is protected by copyright. All rights reserved.