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DOI: 10.1055/s-2008-1072582
An Expedient Three-Component Approach to the Synthesis of α,α-Disubstituted Amines under Barbier-like Conditions
Publikationsverlauf
Publikationsdatum:
31. März 2008 (online)
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Abstract
A series of α,α-disubstituted amines such as diarylmethylamines, 1,2-diarylethylamines, and amino esters have been prepared in acetonitrile using a simple and expedient three-component Mannich-type procedure involving organic halides, aldehyde derivatives, and amines. Reactions are conducted under Barbier-like conditions using simple organic halides and zinc dust for the in situ generation of organozinc reagents.
Key words
amines - halides - multicomponent reactions - organometallic reagents - zinc
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References and Notes
During the course of a previous work dealing with the synthesis of benzylzinc bromide (nonpublished results), we could observe that the reaction is more rapid in MeCN than in THF (>2 times faster). Additionally, it was observed by Gosmini et al. that the solvent is of crucial importance in the cobalt-catalyzed synthesis of arylzinc halides, which cannot be conducted in THF (see ref. 13 for details).
11This is consistent with previous works demonstrating that organozinc reagents have to be used in sufficient excess (>2 equiv) to react efficiently with aldehydes and amines (see ref. 9 for details).
12Coupling products were characterized using 1H NMR (400 MHz, CDCl3), 13C NMR (100 MHz, CDCl3), mass spectrometry, and when useful 19F NMR (376 MHz, CDCl3), and IR spectroscopy.
Data for Selected Compounds N
-(1-Phenyloctan-2-yl)-aniline (1)
Colorless oil; yield 2.21 g (79%). ATR-FTIR (neat): 3405, 3025, 2926, 2855, 1600, 1504, 792, 691 cm-1. 1H NMR: δ = 7.41-7.29 (m, 7 H), 6.79 (t, J = 7.3 Hz, 1 H), 6.72 (d, J = 8.0 Hz, 2 H), 3.75-3.73 (m, 1 H), 3.58 (br s, 1 H), 2.97 (dd, J = 13.6,4.6 Hz, 1 H), 2.91 (dd, J = 13.6, 6.4 Hz, 1 H), 1.69-1.40 (m, 10 H), 0.97 (t, J = 7.0 Hz, 3 H). 13C NMR: δ = 147.7, 138.7, 129.7, 129.5, 128.4, 126.3, 117.0, 113.2, 53.7, 40.2, 34.2, 31.9 29.4, 26.2, 22.7, 14.2. MS: m/z (%) = 191 (13), 190 (100), 118 (9), 106 (39), 91 (6), 55 (6). Anal. Calcd for C20H27N: C, 85.35; H, 9.67; N, 4.98. Found: C, 85.68; H, 9.99; N, 4.57.
Allyl-[2-(4-bromo-phenyl)-1-phenyl-ethyl]-amine (5)
Yellow oil; yield 2.05 g (65%). ATR-FTIR (neat): 3324, 3062, 3025, 2919, 2833, 1642, 1487, 1453, 1071, 1011, 915, 803, 756, 699 cm-1. 1H NMR: δ = 7.40-7.26 (m, 7 H), 6.99 (d, J = 7.9 Hz, 2 H), 5.76-5.88 (m, 1 H), 5.09-5.05 (m, 2 H), 3.90 (t, J = 7.0 Hz, 1 H), 3.14 (dd, J = 14.2, 4.7 Hz, 1 H), 3.01 (dd, J = 14.2, 6.5 Hz, 1 H), 2.92 (d, J = 6.8 Hz, 2 H), 1.50 (br s, 1 H). 13C NMR: δ = 143.1, 137.7, 136.7, 131.4, 131.1, 128.4, 127.3, 127.2, 120.2, 115.8, 63.7, 50.0, 44.5. MS: m/z (%) = 179 (5), 178 (6), 165 (5), 147 (11), 146 (100), 129 (8), 104 (7), 91 (35), 90 (8), 89 (5). Anal. Calcd for C17H18BrN: C, 64.57; H, 5.74; N, 4.43. Found: C, 64.30; H, 5.75; N, 4.30.
Ethyl (
N
-Phenylamino)-3-phenylpropionate (7)
Pale yellow solid; yield 1.48 g (55%); mp 71-73 °C. ATR-FTIR (neat, cm-1): 3384, 3025, 2980, 2925, 1712, 1602, 1218, 760, 689. 1H NMR: δ = 7.42 (d, J = 7.5 Hz, 2 H), 7.36 (t, J = 7.3 Hz, 2 H), 7.28 (t, J = 7.0 Hz, 1 H), 7.14 (t, J = 7.6 Hz, 2 H), 6.71 (t, J = 7.3 Hz, 1 H), 6.60 (d, J = 7.8 Hz, 2 H), 4.87 (t, J = 6.6 Hz, 1 H), 4.64 (br s, 1 H), 4.14 (q, J = 7.1 Hz, 2 H), 2.84 (d, J = 6.2 Hz, 2 H), 1.23 (t, J = 7.1 Hz, 3 H). 13C NMR: δ = 171.2, 146.8, 142.2, 129.2, 128.8, 127.5, 126.3, 117.8, 113.7, 60.8, 55.0, 42.9, 14.2. MS: m/z (%) = 269 (20), 183 (14), 182 (100), 180 (9), 104 (17), 77 (6). Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20. Found: C, 75.65; H, 7.05; N, 5.07.
This constitutes nonoptimized reaction conditions, which may likely be improved during the course of a separate study.