Synlett 2010(3): 483-487  
DOI: 10.1055/s-0029-1219190
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Facile C-N Bond Formation: One-Pot Reaction of Phenols and Amines via Smiles Rearrangement

Hao Yanga, Zhu-Bo Lib, Dong-Soo Shinc, Li-Ying Wangb, Jia-Zhou Zhoub, Hong-Bo Qiaob, Xiao Tianb, Xiao-Yan Mab, Hua Zuo*b
a College of Horticulture and Landscape Architecture, Southwest University, Chongqing 400715, P. R. of China
b College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, P. R. of China
Fax: +86(23)68251225; e-Mail: zuohua@swu.edu.cn;
c Department of Chemistry, Changwon National University, Changwon, 641-773, South Korea
Further Information

Publication History

Received 23 October 2009
Publication Date:
13 January 2010 (online)

Abstract

Diarylamines and arylalkylamines were synthesized in high yields from 2-chlorophenols and amines, activated by chloroacetyl chloride under microwave irradiation (20-60 min) or conventional thermal conditions (3-6 h). The key transformation is believed to proceed via Smiles rearrangement by initial O-alkylation and subsequent cyclization.

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General Procedure of One-Pot Reaction for the C-N Bond Formation (8)
To a magnetically stirred solution of the appropriate primary amine 7 (1.0 mmol) and Cs2CO3 (3.2 mmol) in dry DMF cooled by ice bath were added chloroacetyl chloride (1.2 mmol) and 6 (1.1 mmol). The reaction mixture was then stirred for 30 min at r.t. and placed into microwave oven (600 W, 120 ˚C) and irradiated for 20-60 min or under conventional heating for 3-6 h. The solvent was removed under vacuum and H2O (20 mL) was added into the residue. It was then extracted by EtOAc. The combined organic layers were dried over anhyd MgSO4 and evaporated under vacuum to obtain the crude product. Pure product was obtained by column chromatography on silica gel.

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2-Chloro- N -(4-methoxyphenyl)-5-methylaniline (8l) Orange oil. IR (KBr): ν = 3402, 3038, 2999, 2952, 2930, 2850, 2834, 1600, 1580, 1513, 1455, 1441, 1398, 1294, 1245, 1180, 1044, 829, 794 cm. ¹H NMR (300 MHz, CDCl3): δ = 2.20 (s, 3 H, CH3), 3.81 (s, 3H, OCH3), 5.88 (br s , 1 H, NH), 6.53 (d, J = 8.1 Hz, 1 H, ArH), 6.89 (d, J = 8.7 Hz, 1 H, ArH), 7.12 (d, J = 8.7 Hz, 1 H, ArH), 7.17 (d, J = 8.1 Hz, 1 H, ArH) ppm. ¹³C NMR (75 MHz, CDCl3): δ = 21.3 (CH3), 55.5 (OCH3), 114.4 (CH), 114.7 (CH), 117.1 (C), 120.0 (CH), 124.6 (CH), 129.1 (CH), 134.2 (C), 137.5 (C), 141.7 (C), 156.3 (C) ppm. ESI-MS: m/z (%) = 248 (6) [M + 1], 213 (18), 198 (21), 140 (35), 123 (100), 113 (24), 108 (39).

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2-Chloro- N -(4-methoxyphenyl)acetamide (10) [³7]
White solid; mp 120-122 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 3.81 (s, 3 H, OCH3), 4.19 (s, 2 H, CH2), 6.89 (d, J = 8.8 Hz, 2 H, ArH), 7.44 (d, J = 8.8 Hz, 2 H, ArH), 8.15 (s, 1 H, NH) ppm. ¹³C NMR (75 MHz, CDCl3): δ = 42.8 (OCH3), 55.5 (CH2), 114.2 (CH), 122.0 (CH), 129.6 (C), 157.1 (C), 163.6 (C) ppm.

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2-(2-Chloro-5-methylphenoxy)- N -(4-methoxyphenyl)acetamide (11) White solid; mp 134-136 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 2.35 (s, 3 H, CH3), 3.81 (s, 3 H, OCH3), 4.64 (s, 2 H, CH2), 6.78 (s, 1 H, ArH), 6.82 (d, J = 8.1 Hz, 1 H, ArH), 6.90 (d, J = 8.8 Hz, 2 H, ArH), 7.29 (d, J = 14.0 Hz, 1 H, ArH), 7.52 (d, J = 8.8 Hz, 2 H, ArH), 8.75 (s, 1 H, NH) ppm. ¹³C NMR (75 MHz, CDCl3): δ = 21.3 (CH3), 55.5 (OCH3), 68.3 (CH2), 114.2 (CH), 115.1 (C), 119.8 (C), 121.6 (CH), 123.8 (C), 130.0 (C), 138.6 (C), 152.5 (C), 161.8 (C), 165.3 (C) ppm.

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4-Phenethyl-2 H -benzo[ b ][1,4]oxazin-3 (4 H )-one (9b) White solid. IR (KBr): ν = 3421, 2930, 1682, 1409, 1058, 743 cm. ¹H NMR (300 MHz, CDCl3): δ = 2.96 (t, J = 9.0 Hz, 2 H, CH2), 4.14 (t, J = 9.0 Hz, 2 H, CH2), 4.58 (s, 2 H, OCH2CO), 7.00-7.02 (m, 4 H, ArH), 7.25-7.34 (m, 5 H, ArH) ppm. ¹³C NMR (75 MHz, CDCl3): δ = 33.5 (CH2), 42.7 (CH2), 67.7 (OCH2CO), 114.9 (CH), 117.4 (CH), 123.0 (CH), 124.0 (CH), 126.9 (CH), 128.5 CH), 128.7 (CH), 128.9 (CH), 138.2 (C), 145.5 (C), 164.3 (CO) ppm.