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

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.

Key words

C-N coupling - one pot - amine - Smiles rearrangement - synthesis

References and Notes

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32

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.

33

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^-¹. ^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).

34

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.

35

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.

36

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^-¹. ^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.