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Synlett 2006(2): 283-287  
DOI: 10.1055/s-2005-923602
LETTER
© Georg Thieme Verlag Stuttgart · New York

Thia-Michael Addition Reactions Using 2-[Bis(alkylthio)methylene]-3-oxo-N-o-tolylbutanamides as Odorless and Efficient Thiol Equivalents

Dewen Dong*, Haifeng Yu, Yan Ouyang, Qun Liu*, Xihe Bi, Yumei Lu
Department of Chemistry, Northeast Normal University, Changchun, 130024, P. R. of China
Fax: +86(431)5098635; e-Mail: dongdw663@nenu.edu.cn;
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Publication History

Received 22 October 2005
Publication Date:
23 December 2005 (online)

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Abstract

A series of 2-[bis(alkylthio)methylene]-3-oxo-N-o-tolylbutanamides 1 have been investigated as nonthiolic and odorless thiol equivalents in thia-Michael addition reactions. The cleavage of compounds 1 is initiated by NaOH in EtOH; the in situ generated thiolate anions undergo facile conjugate addition to α,β-unsaturated carbonyl compounds 2 affording the corresponding β-keto sulfides 3 in very high yields. Meanwhile, 3-oxo-N-o-tolylbutanamide 4, the precursor of compounds 1, can be recovered from the novel thia-Michael addition reactions as a byproduct in good yield.

Key words

β-keto sulfide - Michael addition - α,β-unsaturated carbonyl compound - α-oxo ketene-S,S-acetal - thiol equivalent

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Selected data for compounds 1: 2-[Bis(methylthio)meth-ylene]-3-oxo- N - o -tolylbutanamide ( 1a) Yellow solid; mp 102-104 °C. IR (KBr, neat): 3361, 2980, 1647, 1523, 1453 cm-1. 1H NMR (500 MHz, CDCl3): δ = 2.31 (s, 3 H), 2.48 (s, 6 H), 2.52 (s, 3 H), 7.06-7.09 (m, 1 H), 7.18-7.25 (m, 2 H), 8.05 (d, J = 8.0 Hz, 1 H), 8.21 (br, 1 H). Anal. Calcd for C14H17NO2S2: C, 56.92; H, 5.80; N, 4.74. Found: C, 56.84; H, 5.77; N, 4.76. 2-[Bis(butylthio)methylene]-3-oxo- N - o -tolylbutanamide ( 1c) Yellow solid; mp 48-50 °C. IR (KBr, neat): 3345, 2957, 1650, 1526, 1454 cm-1. 1H NMR (500 MHz, CDCl3): δ = 0.90-0.93 (m, 6 H), 1.39-1.46 (m, 4 H), 1.60-1.66 (m, 4 H), 2.31 (s, 3 H), 2.53 (s, 3 H), 2.92-2.95 (m, 4 H), 7.06-7.09 (m, 1 H), 7.18-7.24 (m, 2 H), 8.02 (d, J = 8.0 Hz, 1 H), 8.23 (br, 1 H). Anal. Calcd for C20H29NO2S2: C, 63.28; H, 7.70; N, 3.69. Found: C, 63.36; H, 7.67; N, 3.64.

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Selected data for compounds 3: 3-(Methylthio)-1,3-di-phenylpropan-1-one (3a) White crystals, mp 55-57 °C. IR (KBr, neat): 3059, 2912, 1685, 1595, 1494, 1225 cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.93 (s, 3 H), 3.55 (m, 2 H), 4.47 (m, 1 H), 7.21-7.24 (m, 1 H), 7.30-7.33 (m, 2 H), 7.40-7.46 (m, 4 H), 7.51-7.57 (m, 1 H), 7.92 (d, J = 8.0 Hz, 2 H). Anal. Calcd for C16H16OS: C, 74.96; H, 6.29. Found: C, 74.85; H, 6.33. Ethyl 3-(methylthio)-3-phenylpropanoate (3r) Colorless liquid. IR (KBr, neat): 3028, 2980, 1736, 1601, 1490, 1215 cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.14-1.16 (m, 3 H), 1.90 (s, 3 H), 2.82-2.93 (m, 2 H), 4.03-4.09 (m, 2 H), 4.18-4.21 (m, 1 H), 7.21-7.24 (m, 1 H), 7.25-7.33 (m, 4 H). Anal. Calcd for C12H16O2S: C, 64.25, H, 7.19. Found: C, 64.34, H 7.13. Ethyl 3-(ethylthio)-3-phenyl-propanoate ( 3s) Colorless liquid. IR (KBr, neat): 3061, 2976, 1732, 1601, 1492, 1213 cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.13-1.17 (m, 6 H), 2.30-2.36 (m, 2 H), 2.81-2.90 (m, 2 H), 4.04-4.30 (m, 2 H), 4.28-4.32 (m, 1 H), 7.21-7.24 (m, 1 H), 7.28-7.35 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 13.8, 14.1, 24.9, 41.3, 44.7, 60.4, 127.1, 127.4 (2 C), 128.2 (2 C), 141.2, 170.5. Anal. Calcd for C13H18O2S: C, 65.51; H, 7.61. Found: C, 65.59; H, 7.57. Ethyl 3-(butyl-thio)-3-phenylpropanoate ( 3t) Colorless liquid. IR (KBr, neat): 3061, 2958, 1737, 1602, 1489, 1214 cm-1. 1H NMR (500 MHz, CDCl3): δ = 0.84 (t, 3 H), 1.15 (t, 3 H), 1.27-1.36 (m, 2 H), 1.44-1.51 (m, 2 H), 2.27-2.37 (m, 2 H), 2.81-2.91 (m, 2 H), 4.02-4.09 (m, 2 H), 4.25-4.28 (m, 1 H), 7.21-7.24 (m, 1 H), 7.29-7.35 (m, 4 H). Anal. Calcd for C15H22O2S: C, 67.63; H, 8.32. Found: C, 67.55; H, 8.34. Ethyl 3-(allylthio)-3-phenylpropanoate ( 3u): Colorless liquid. IR (KBr, neat): 3079, 2958, 1737, 1599, 1454, 1249 cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.14-1.17 (m, 3 H), 2.81-2.93 (m, 3 H), 3.00-3.03 (m, 1 H), 4.04-4.08 (m, 2 H), 4.25-4.28 (m, 1 H), 5.04-5.11 (m, 2 H), 5.72-5.80 (m, 1 H), 7.22-7.25 (m, 1 H), 7.30-7.35 (m, 4 H). Anal. Calcd for C14H18O2S: C, 67.16; H, 7.25. Found: C, 67.25; H, 7.19. Ethyl 3-(benzyl-thio)-3-phenylpropanoate ( 3v) Colorless liquid. IR (KBr, neat): 3061, 2980, 1735, 1601, 1584, 1493, 1370 cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.10-1.14 (m, 3 H), 2.81-2.88 (m, 2 H), 3.46 (d, J = 13 Hz, 1 H), 3.56 (d, J = 13 Hz, 1 H), 4.00-4.06 (m, 2 H), 4.15-4.18 (m, 1 H), 7.21-7.35 (m, 10 H). 13C NMR (125 MHz, CDCl3): δ = 13.8, 35.4, 41.2, 44.7, 60.4, 126.8, 127.2, 127.7 (2 C), 128.2 (2 C), 128.3 (2 C), 128.7 (2 C), 137.5, 140.8, 170.3. Anal. Calcd for C18H20O2S: C, 71.96; H, 6.71. Found: C, 71.87; H, 6.75.