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DOI: 10.1055/s-0029-1219190
A Facile C-N Bond Formation: One-Pot Reaction of Phenols and Amines via Smiles Rearrangement
Publication History
Publication Date:
13 January 2010 (online)
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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
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
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.
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.
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.
364-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.