Download PDF
Synlett 2007(1): 0151-0155  
DOI: 10.1055/s-2006-958438
LETTER
© Georg Thieme Verlag Stuttgart · New York

NaOH-Promoted Thiolysis of Oxiranes Using 2-[Bis(alkylthio)methylene]-3-oxo-N-o-tolylbutanamides as Odorless Thiol Equivalents

Haifeng Yua,b, Dewen Dong*a, Yan Ouyanga, Yan Wanga, Qun Liu*a
a Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. of China
Fax: +86(431)5098635; e-Mail: dongdw663@nenu.edu.cn;
b Department of Chemistry, Anshan Normal College, Anshan 114007, P. R. of China
Further Information

Publication History

Received 30 September 2006
Publication Date:
20 December 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

A convenient and efficient protocol for the thiolysis of oxiranes using 2-[bis(alkylthio)methylene]-3-oxo-N-o-tolylbutan­amides as thiol equivalents has been developed. Promoted by sodium hydroxide (NaOH) in ethanol at room temperature, the cleavage commences and the generated thiolate anions undergo nucleophilic addition in situ. β-Hydroxy sulfides were obtained in high yields along with good β-regioselectivity, and trans β-hydroxy sulfides were also isolated. The thiolysis of one α,β-epoxyketone product with the thiol equivalents was accomplished to afford the corresponding α-carbonyl sulfides in excellent yields. In all the cases, 3-oxo-N-o-tolylbutanamide, the precursor of the thiol equivalents, could be recovered in the novel thiolysis process as a byproduct in good yield.

Key words

α-carbonyl sulfides - epoxides - β-hydroxy sulfides - α-oxo ketene-S,S-acetals - thiolysis

18

Thiolysis of 2 with 1 (4a as Example); Typical Procedure: To a 25 mL flask containing NaOH (1.0 mmol) in EtOH (5 mL) were added 1a (1.0 mmol) and 2a (2.0 mmol) under stirring. The mixture was stirred at r.t. for about 50 min, after which time the reaction was complete as indicated by TLC. The resulting mixture was neutralized with aq HCl (0.1 N, 10 mL), and extracted with Et2O (3 × 15 mL). The combined organic extracts were washed with H2O (3 × 15 mL), dried over MgSO4, filtered and concentrated in vacuo. Separation was carried out by silica gel chromatography using PE-Et2O (10:1) as eluent to afford product 4a in 90% yield. Selected Data for Compounds 4-6: Compounds 4a, 4d, 4i and 5d are known, and were identified by 1H NMR, IR spectroscopy and elemental analyses, the data for these compounds are in good agreement with those in literature (refs. 6e-g).
1-(Butylthio)propan-2-ol (4b): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 0.83-0.86 (m, 3 H), 1.17-1.20 (m, 3 H), 1.31-1.37 (m, 2 H), 1.48-1.51 (m, 2 H), 2.36-2.42 (m, 1 H), 2.45-2.49 (m, 2 H), 2.61-2.65 (m, 1 H), 2.91 (br, 1 H), 3.77 (br, 1 H). 13C NMR (125 MHz, CDCl3): δ = 13.5, 21.8 (2 × C), 31.7, 31.8, 41.5, 65.3. IR (KBr, neat): 3340, 2925, 1734, 1539, 1459, 1284 cm-1. Anal. Calcd for C7H16OS: C, 56.71; H, 10.88. Found: C, 56.82; H, 10.96.
1-(Ethylthio)propan-2-ol (4c): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 0.80-0.86 (m, 3 H), 1.25-1.28 (m, 3 H), 2.41-2.46 (m, 1 H), 2.54-2.58 (m, 2 H), 2.63 (br, 1 H), 2.73-2.76 (m, 1 H), 3.83-3.85 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ = 15.8, 21.7, 31.6, 41.2, 65.4. IR (KBr, neat): 2955, 2869, 1458, 1247, 1200 cm-1. Anal. Calcd for C5H12OS: C, 49.96; H, 10.06. Found: C, 49.81; H, 10.14.
2-(Butylthio)-1-phenylethanol (4e): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 0.91-0.94 (m, 3 H), 1.38-1.45 (m, 2 H), 1.56-1.62 (m, 2 H), 2.53-2.56 (m, 2 H), 2.70-2.74 (m, 1 H), 2.91-2.94 (m, 1 H), 3.10 (br, 1 H), 4.72-4.74 (m, 1 H), 7.28-7.31 (m, 1 H), 7.31-7.39 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 13.9, 22.2, 31.9, 32.0, 42.3, 71.8, 126.1 (2 × C), 128.1, 128.8 (2 × C), 142.8. IR (KBr, neat): 3426, 3029, 2926, 1740, 1456, 1274 cm-1. Anal. Calcd for C12H18OS: C, 68.52; H, 8.63. Found: C, 68.64; H, 8.72.
2-(Butylthio)-2-phenylethanol (5e): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 0.84-0.87 (m, 3 H), 1.31-1.39 (m, 2 H), 1.48-1.54 (m, 2 H), 2.09 (br, 1 H), 2.42-2.45 (m, 2 H), 3.83-3.87 (m, 2 H), 3.94-3.97 (m, 1 H), 7.26-7.28 (m, 1 H), 7.29-7.38 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 13.9, 22.2, 31.1, 31.8, 53.2, 65.8, 127.9, 128.2 (2 × C), 129.0 (2 × C), 139.1. IR (KBr, neat): 3386, 3028, 2927, 1713, 1538, 1456, 1276 cm-1. Anal. Calcd for C12H18OS: C, 68.52; H, 8.63. Found: C, 68.67; H, 8.58.
2-(Ethylthio)-1-phenylethanol (4f): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 1.25-1.30 (m, 3 H), 2.53-2.58 (m, 2 H), 2.70-2.75 (m, 1 H), 2.90-2.94 (m, 1 H), 4.71-4.73 (m, 1 H), 7.26-7.30 (m, 1 H), 7.31-7.38 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 15.1, 26.3, 41.8, 71.9, 126.1 (2 × C), 128.1, 128.8 (2 × C), 142.7. IR (KBr, neat): 3424, 3029, 2921, 1720, 1540, 1451, 1265 cm-1. Anal. Calcd for C10H14OS: C, 65.89; H, 7.74. Found: C, 65.73; H, 7.62.
2-(Ethylthio)-2-phenylethanol (5f ): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 1.19-1.22 (m, 3 H), 2.04-2.07 (m, 1 H), 2.42-2.49 (m, 2 H), 3.84-3.89 (m, 2 H), 3.97-4.00 (m, 1 H), 7.26-7.28 (m, 1 H), 7.28-7.35 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 15.0, 25.4, 52.8, 65.8, 127.9, 128.3 (2 × C), 129.0 (2 × C), 140.0. IR (KBr, neat): 3334, 3028, 2924, 1712, 1540, 1453, 1265 cm-1. Anal. Calcd for C10H14OS: C, 65.89; H, 7.74. Found: C, 65.77; H, 7.81.
2-(Methylthio)-1-phenylethanol (4g): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 2.13 (s, 3 H), 2.71-2.76 (m, 1 H), 2.86-2.89 (m, 1 H), 3.02 (br, 1 H), 4.76-4.78 (m, 1 H), 7.29-7.31 (m, 1 H), 7.32-7.38 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 15.4, 44.0, 71.1, 125.7 (2 × C), 127.8, 128.4 (2 × C), 142.4. IR (KBr, neat): 3421, 3029, 2915, 1721, 1540, 1449, 1235 cm-1. Anal. Calcd for C9H12OS: C, 64.25; H, 7.19. Found: C, 64.13; H, 7.24.
2-(Methylthio)-2-phenylethanol (5g): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 1.99 (s, 3 H), 2.06 (br, 1 H), 3.87-3.90 (m, 3 H), 7.26-7.29 (m, 1 H), 7.30-7.37 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 13.7, 54.0, 64.8, 127.6, 127.9 (2 × C), 128.6 (2 × C), 139.0. IR (KBr, neat): 3358, 3027, 2923, 1722, 1597, 1458, 1269 cm-1. Anal. Calcd for C9H12OS: C, 64.25; H, 7.19. Found: C, 64.36; H, 7.15.
2-(Allylthio)-1-phenylethanol (4h): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 2.66-2.71 (m, 1 H), 2.86-2.90 (m, 1 H), 2.94 (br, 1 H), 3.10-3.19 (m, 2 H), 4.72-4.74 (m, 1 H), 5.10-5.15 (m, 2 H), 5.75-5.83 (m, 1 H), 7.28-7.31 (m, 1 H), 7.32-7.37 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 34.9, 40.2, 72.0, 118.0, 126.1 (2 × C), 128.1, 128.8 (2 × C), 134.3, 142.9. IR (KBr, neat): 3425, 3030, 2914, 1715, 1540, 1452, 1228 cm-1. Anal. Calcd for C11H14OS: C, 68.00; H, 7.26. Found: C, 68.21; H, 7.21.
2-(Allylthio)-2-phenylethanol (5h): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 1.94-1.96 (m, 1 H), 2.98-3.02 (m, 1 H), 3.11-3.15 (m, 1 H), 3.85-3.88 (m, 2 H), 3.94-3.97 (m, 1 H), 5.05-5.12 (m, 2 H), 5.75-5.81 (m, 1 H), 7.27-7.29 (m, 1 H), 7.30-7.37 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 34.3, 51.6, 65.9, 117.8, 127.9, 128.5 (2 × C), 129.0 (2 × C), 134.4, 139.7. IR (KBr, neat): 3388, 3028, 2919, 1711, 1538, 1454, 1230 cm-1. Anal. Calcd for C11H14OS: C, 68.00; H, 7.26. Found: C, 68.12; H, 7.19. 2-(Butylthio)cyclohexanol (4j): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 0.89 (t, J = 7.5 Hz, 3 H), 1.22-1.29 (m, 3 H), 1.36-1.44 (m, 3 H), 1.51-1.57 (m, 2 H), 1.68-1.73 (m, 2 H), 2.04-2.10 (m, 2 H), 2.31-2.37 (ddd, J = 4.0, 9.5, 12.5 Hz, 1 H), 2.53 (m, 2 H), 3.03 (br, 1 H), 3.25-3.27 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ = 13.6, 22.0, 24.4, 26.2, 29.4, 32.3, 32.9, 33.7, 53.4, 72.0. IR (KBr, neat): 3450, 2930, 1449, 1227 cm-1. Anal. Calcd for C10H20OS: C, 63.77; H, 10.70. Found: C, 63.89; H, 10.62.
2-(Benzylthio)-1-phenylethanone (6a): colorless crystal; mp 68-70 °C. 1H NMR (500 MHz, CDCl3): δ = 3.68 (s, 2 H), 3.76 (s, 2 H), 7.25-7.27 (m, 2 H), 7.32-7.48 (m, 3 H), 7.47-7.49 (m, 2 H), 7.51-7.53 (m, 1 H), 7.93-7.95 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 35.6, 35.8, 127.0, 128.3 (2 × C), 128.4 (2 × C), 128.5 (2 × C), 129.0 (2 × C), 133.0, 135.1, 137.0, 194.2. IR (KBr, neat): 3058, 2923, 1672, 1545, 1450, 1200 cm-1. Anal. Calcd for C15H14OS: C, 74.34; H, 5.82. Found: C, 74.48; H, 5.77.
2-(Butylthio)-1-phenylethanone (6b): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 0.82-0.92 (m, 3 H), 1.34-1.42 (m, 2 H), 1.54-1.60 (m, 2 H), 2.54-2.57 (m, 2 H), 3.78 (s, 2 H), 7.45-7.48 (m, 2 H), 7.55-7.58 (m, 1 H), 7.95-7.98 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 12.7, 20.9, 30.0, 31.0, 36.1, 127.6 (2 × C), 127.8 (2 × C), 132.3, 134.2, 193.5. IR (KBr, neat): 3021, 2950, 1739, 1687, 1511, 1461, 1274 cm-1. Anal. Calcd for C12H16OS: C, 69.19; H, 7.74. Found: C, 69.38; H, 7.67.
2-(Ethylthio)-1-phenylethanone (6c): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 1.27 (t, J = 7.5 Hz, 3 H), 2.59 (q, J = 7.5 Hz, 2 H), 3.80 (s, 2 H), 7.46-7.49 (m, 2 H), 7.56-7.59 (m, 1 H), 7.98 (d, 2 H). 13C NMR (125 MHz, CDCl3): δ = 13.1, 25.3, 35.7, 127.3, 127.7 (2 × C), 127.8 (2 × C), 132.3, 193.5. IR (KBr, neat): 3061, 2967, 1675, 1450, 1276 cm-1. Anal. Calcd for C10H12OS: C, 66.63; H, 6.71. Found: C, 66.51; H, 6.65.
2-(Methylthio)-1-phenylethanone (6d): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 2.13 (s, 3 H), 3.76 (s, 2 H), 7.45-7.48 (m, 2 H), 7.56-7.59 (m, 1 H), 7.95-7.98 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 14.9, 38.0, 127.7, 127.8, 127.9 (2 × C), 132.4, 134.1, 193.0. IR (KBr, neat): 3060, 2918, 1672, 1579, 1447, 1278 cm-1. Anal. Calcd for C9H10OS: C, 65.02; H, 6.06. Found: C, 65.20; H, 6.12.
2-(Allylthio)-1-phenylethanone (6e): colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 3.18 (d, J = 7.5 Hz, 2 H), 3.76 (s, 2 H), 5.15-5.21 (m, 2 H), 5.74-5.80 (m, 1 H), 7.45-7.48 (m, 2 H), 7.55-7.58 (m, 1 H), 7.96 (d, J = 7.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 34.9, 35.7, 118.8, 128.9, 129.0, 129.1, 129.2, 133.2, 133.6, 134.2, 194.7. IR (KBr, neat): 3061, 2917, 1676, 1540, 1449, 1275 cm-1. Anal. Calcd for C11H12OS: C, 68.71; H, 6.29. Found: C, 68.58; H, 6.37.