S1

Supporting Information

Direct Amination of Azoles via Catalytic C−H, N−H Coupling

Daiki Monguchi, Taiki Fujiwara, Hirotoshi Furukawa, and Atsunori Mori*

Department of Chemical Science and Engineering, Kobe University, 1-1

Rokkodai, Nada, Kobe 657-8501, Japan

Experimental Section

General. 1H NMR (500 MHz) and 13C NMR (125 MHz) spectra were measured on a

Brucker Avence 500 spectrometer. The chemical shifts were expressed in ppm with

CHCl3 (7.26 ppm for 1H) or CDCl3 (77.0 ppm for 13C) as internal standards. IR spectra

were recorded on PERKIN ELMER FT-IR Spectrometer SPECTRUM 1000. High

resolution mass spectra (HRMS, EI) were measured by JEOL JMS-700 MStation at the

Graduate School of Material Science, Nara Institute of Science and Technology. For

thin layer chromatoraphy (TLC) analyses throughout this work, Merck precorted TLC

plates (silica gel 60 F254) were used.

General procedure for the oxidative copper-catalyzed amination of heteroaromatic

compounds.

A solution of Cu(OAc)2 (7.3 mg, 0.04 mmol), PPh3 (21 mg, 0.08 mmol), benzothiazole

1a (22 μL, 0.2 mmol), N-methylaniline 2a (88 μL, 0.8 mmol) and NaOAc (66 mg, 0.8 mmol) in 1 mL of xylene was stirred at 140 ºC for 20 h under O2. After cooling to room

temperature, the mixture was passed through a Celite pad, which was washed with

chloroform repeatedly. The filtrate was washed with water three times. The organic

layer was concentrated under reduced pressure to leave a crude oil, which was purified

by column chromatography on silica gel to afford 39 mg of 3a as a colorless oil (81%).

N-Benzothiazol-2-yl-N-propyl-4-methylbenzenesulfonamide (3c): 1H NMR (500 MHz, CDCl3) δ 0.98 (t, J = 7.5 Hz, 3H), 1.78-1.86 (m,

2H), 2.37 (s, 3H), 4.00-4.03 (m, 2H), 7.24-7.29 (m, 3H), 7.36-7.39 (m,

1H), 7.74 (d, J = 9.1 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ

11.2, 21.7, 21.9, 51.8, 120.9, 121.7, 124.3, 126.1, 127.3, 130.1, 133.4, 135.6, 144.9,

N

SN

Ts

nPr

S2

149.7, 160.2; IR (neat) 1011, 1088, 1172, 1186, 1224, 1225, 1307, 1361, 1443, 1457,

1496, 1596, 1699, 2873, 2965, 3062 cm-1; HRMS found: m/z 346.0811. Calcd for

346.0810.

N-(4,5-Dimethyl-thiazol-2yl)-N-methylaniline (5a): 1H NMR (500

MHz, CDCl3) δ 2.14 (d, J = 0.6 Hz, 3H), 2.18 (d, J = 0.6 Hz, 3H),

3.48 (s, 3H), 7.16-7.23 (m, 1H), 7.33-7.43 (m, 4H); 13C NMR (125

MHz, CDCl3) δ 11.1, 14.9, 40.0, 114.4, 124.7, 125.9, 129.7, 147.0, 166.4; IR (neat)

1131, 1287, 1374, 1410, 1516, 1597, 1678, 2851, 2917, 3035 cm-1; HRMS found: m/z

218.0878. Calcd for 218.0878.

N-Benzoxazol-2-yl-diphenylamine (7b): 1H NMR (500 MHz,

CDCl3) δ 7.03 (t, J = 7.6 Hz, 1H), 7.14 (t, J = 7.7 Hz, 1H), 7.18-7.22

(m, 3H), 7.27-7.37 (m, 8H), 7.41 (d, J = 7.6 Hz, 1H); 13C NMR (125

MHz, CDCl3) δ 109.4, 117.7, 122.2, 124.4, 126.2, 126.6, 129.6, 142.2, 142.8, 148.6,

160.3; IR (neat) 1006, 1209, 1242, 1366, 1456, 1495, 1557, 1625, 2852, 2922, 3057

cm-1; HRMS found: m/z 286.1106. Calcd for 286.1103.

Ethyl 4-[2-(Methyl(phenyl)amino)-thiazol-5-yl] benzoate

(14a): 1H NMR (500 MHz, CDCl3) δ 1.38 (t, J = 7.0 Hz, 3H),

3.57 (s, 3H), 4.36 (q, J = 7.2 Hz, 2H), 7.29-7.33 (m, 1H), 7.39-7.48 (m, 6H), 7.57 (s,

1H), 7.95 (d, J = 8.8 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 14.5, 40.3, 61.0, 124.8,

125.4, 126.5, 127.1, 128.3, 130.1, 130.3, 136.9, 137.0, 146.2, 166.4, 170.5; IR (neat)

1023, 1107, 1183, 1275, 1366, 1404, 1452, 1564, 1605, 1709, 2927, 3035, 3056 cm-1;

HRMS found: m/z 338.1089. Calcd for 338.1092.

Ethyl 4-(2-Diphenylaminothiazol-5-yl)-benzoate (14b): 1H NMR (500 MHz, CDCl3) δ 1.39 (t, J = 7.0 Hz, 3H), 4.37

(q, J = 7.3 Hz, 2H), 7.26-7.30 (m, 2H), 7.38-7.46 (m, 10H),

7.62 (s, 1H), 7.98 (d, J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 14.5, 61.2, 125.2,

126.2, 127.3, 128.2, 129.3, 130.2, 130.4, 134.5, 135.8, 144.4, 166.2, 169.2; IR (neat)

1021, 1107, 1184, 1274, 1366, 1409, 1446, 1477, 1605, 1711, 2927, 2978, 3062 cm-1;

HRMS found: m/z 400.1245. Calcd for 400.1250.

N

ONPh2

N

Sp-EtO2CC6H4 NPh2

N

Sp-EtO2CC6H4 N

Me

Ph

N

SN

Me

PhMe

Me

S3

Other coupling products 3a1), 3b2), 7a3), 7d4), 7e3) and 9a1) are known in the literature.

References

1 Hooper, M. W.; Utsunomiya, M.; Hartwig, J. F. J. Org. Chem. 2003, 68, 2861-2873.

2 Muthusamy, S.; Pharmasivam, R.; Ramakrishnan, V. T. J. Heterocyclic. Chem.

1991, 28, 759-763.

3 Khalaf, A. I.; Alvarez, R. G.; Suckling, C. J.; Waigh, R. D. Tetrahedron 2000, 56,

8567-8571.

4 Hwang, J. Y.; Gong, Y.-D. J. Comb. Chem., 2006, 8, 297-303.

S4

1H NMR spectrum of 3c

13C NMR spectrum of 3c

N

SN

Ts

nPr

N

SN

Ts

nPr

S5

1H NMR spectrum of 5a

13C NMR spectrum of 5a

N

SN

Me

PhMe

Me

N

SN

Me

PhMe

Me

S6

1H NMR spectrum of 7b

13C NMR spectrum of 7b

N

ONPh2

N

ONPh2

S7

1H NMR spectrum of 14a

13C NMR spectrum of 14a

N

Sp-EtO2CC6H4 N

Me

Ph

N

Sp-EtO2CC6H4 N

Me

Ph

S8

1H NMR spectrum of 14b

13C NMR spectrum of 14b

N

Sp-EtO2CC6H4 NPh2

N

Sp-EtO2CC6H4 NPh2