The Journal of Organic Chemistry
Note
in the NMR solvents (CDCl3: 7.26 ppm, 13C NMR solvents CDCl3:
77.0 ppm). The APCI-MS, ESI-MS, and LC-MS analysis were
recorded on a triple-stage quadrupole mass spectrometer; the HRMS
spectra were recorded as ESI-HRMS on a LC-Q-TOF (UHD) mass
spectrometer. IR spectra were recorded on an FTIR spectropho-
tometer. Melting points were measured in a digital melting point
apparatus.
[M + H]+ Calcd for C16H21O2S 277.0, found 277.0; HRMS (ESI) m/z
[M + H]+ Calcd for C16H21O2S 277.1257, found 277.1262.
S-Cyclohexyl 2-(3-Nitrophenyl)-2-oxoethanethioate 4g. Yellow
1
gummy solid, yield: 122 mg (71%); H NMR (400 MHz, CDCl3) δ
8.20 (m, 2H), 7.19 (t, 2H), 3.70 (m, 1H), 2.20 (m, 2H), 1.78 (m, 2H),
1.53 (m, 4H), 1.35 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 192.6,
184.9, 167.8, 165.7, 133.72, 133.70, 133.65, 133.62, 116.26, 116.24,
116.08, 116.06, 42.7, 32.7, 25.8, 25.4; IR (CHCl3, cm−1) ν 1679, 1597;
LC-MS (APCI) m/z [M + H]+ Calcd for C14H16NO4S 294.0, found
294.0; HRMS (ESI) m/z [M + H]+ Calcd for C14H16NO4S 294.0795,
found 294.0789.
S-Cyclohexyl 2-(Benzo[d][1,3]dioxol-5-yl)-2-oxoethanethioate
4h. Yellow solid (mp: 74−76); yield: 123 mg (72%); 1H NMR
(400 MHz, CDCl3) δ 7.80 (d, J = 8.0 Hz, 2H), 7.56 (s, 1H), 6.89 (d, J
= 8.4 Hz, 1H), 6.07 (s, 2H), 3.66 (m, 1H), 2.01−1.99 (m, 2H), 1.77−
1.74 (m, 2H), 1.54−1.46 (m, 4H), 1.36−1.29 (m, 2H); 13C NMR
(125 MHz, CDCl3) δ 193.0, 184.9, 153.5, 148.4, 128.5, 126.1, 109.5,
108.3, 102.2, 42.6, 32.8, 25.9, 25.4; IR (CHCl3, cm−1) ν 1664, 1599;
LC-MS (APCI) m/z [M + H]+ Calcd for C15H17O4S 293.0, found
293.0; HRMS (ESI) m/z [M + H]+ Calcd for C15H17O4S 293.0842,
found 293.0835.
S-Cyclohexyl 2-Oxo-2-(p-tolyl)ethanethioate 4i. Yellow gummy
solid, yield: 116 mg (76%); 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J
= 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 3.70 (m, 1H), 2.43 (s, 3H),
2.20−2.00 (m, 2H), 1.77−1.75 (m, 2H), 1.52−1.47 (m, 4H), 1.34 (m,
2H); 13C NMR (125 MHz, CDCl3) δ 193.0, 186.4, 146.1, 130.8,
129.5, 129.1, 42.6, 32.86, 32.82, 25.9, 25.4, 21.9; IR (CHCl3, cm−1) ν
1678, 1606; LC-MS (APCI) m/z [M − H]− Calcd for C15H19O2S
263.0, found 263.0; HRMS (ESI) m/z [M + H]+ Calcd for C15H19O2S
263.1100, found 263.1104.
General Procedure for Synthesis of α-Ketothioesters (4). A
reaction vessel was charged with 2-oxoaldehyde 1 (0.592 mmol),9b
pyrrolidine 2a (50 mol %), and the respective thiol 3 (0.888 mmol) in
2 mL of toluene solvent. The reaction mixture was allowed to stir at
room temperature (30 °C) for 2 h. After completion of the reaction,
solvent was removed under reduced pressure. The crude product was
purified by column chromatography on silica gel (100−200#) using
hexane and ethyl acetate (99.5:0.5) as eluent. It afforded the
corresponding product 4 in good yields (55−76%).
Analytical Data for Compound 4. S-Cyclohexyl 2-Oxo-2-
phenylethanethioate 4a. Yellow gummy solid, yield: 105 mg
1
(72%); H NMR (400 MHz, CDCl3) δ 8.11(d, J = 7.2 Hz, 2H),
7.66 (t, J = 7.2 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 3.77 (m, 1H), 2.03
(m, 2H), 1.78 (m, 2H), 1.53 (m, 4H), 1.37 (m, 2H); 13C NMR (125
MHz, CDCl3) δ 191.3, 185.3, 133.3, 133.2, 129.29, 129.27, 127.37,
127.35, 41.2, 31.3, 24.4, 24.0; IR (CHCl3, cm-1) ν 1673, 1596; LC-MS
(APCI) m/z [M + H]+ Calcd for C14H17O2S 249.0, found 249.0;
HRMS (ESI) m/z [M + H]+ Calcd for C14H17O2S 249.0944, found
249.0948.
S-Cyclohexyl 2-(4-Bromophenyl)-2-oxoethanethioate 4b. Yellow
solid (mp: 80−83); yield: 124 mg (65%); 1H NMR (400 MHz,
CDCl3) δ 8.00 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H), 3.70 (m,
1H), 2.02−1.99 (m, 2H), 1.78−1.76 (m, 2H), 1.56−1.47 (m, 4H),
1.34−1.39 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 192.0, 185.3,
131.97, 131.94, 130.3, 130.2, 42.5, 32.4, 25.6, 25.3. IR (CHCl3, cm−1)
ν 1673, 1583; LC-MS (APCI) m/z [M + H]+ Calcd for C14H16BrO2S
327.0, found 327.0; HRMS (ESI) m/z [M + H]+ Calcd for
C14H16BrO2S 327.0049, found 327.0047.
S-Butyl 2-Oxo-2-(p-tolyl)ethanethioate 4j. Yellow gummy solid,
1
yield: 75 mg (54%); H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0
Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 3.06 (t, J = 7.2 Hz, 2H), 2.43 (s,
3H), 1.68 (m, 2H), 1.48 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H); 13C NMR
(125 MHz, CDCl3) δ 193.3, 186.1, 146.1, 130.8, 129.5, 129.1, 31.1,
28.5, 22.0, 21.8, 13.5; IR (CHCl3, cm−1) ν 1677, 1605; LC-MS
(APCI) m/z [M + H]+ Calcd for C13H17O2S 237.0, found 237.0;
HRMS (ESI) m/z [M + H]+ Calcd for C13H17O2S 237.0944, found
237.0949.
S-Cyclohexyl 2-(4-Fluorophenyl)-2-oxoethanethioate 4c. Yellow
1
gummy solid, yield: 106 mg (68%); H NMR (400 MHz, CDCl3) δ
8.20 (dd, J = 5.2, 7.6 Hz, 2H), 7.19 (t, J = 8.4 Hz, 2H), 3.70 (m, 1H),
2.02−1.99 (m, 2H), 1.77−1.75 (m, 2H), 1.56−1.47 (m, 4H), 1.34−
1.31 (m, 2H); 13C NMR (125 MHz, CDCl3), δ 192.6, 184.9, 167.2,
165.7, 133.7, 133.6, 42.7, 32.7, 25.9, 25.4; IR (CHCl3, cm−1) ν 1679,
1597; LC-MS (APCI) m/z [M + H]+ Calcd for C14H16FO2S 267.0,
found 267.0; HRMS (ESI) m/z [M + H]+ Calcd for C14H16FO2S
267.0850, found 267.0852.
S-Cyclohexyl 2-(4-Chlorophenyl)-2-oxoethanethioate 4d. Yellow
solid (mp: 73−75); yield: 103 mg (62%); 1H NMR (400 MHz,
CDCl3) δ 8.08 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 3.70 (m,
1H), 2.02−1.99 (m, 2H), 1.78−1.74 (m, 2H), 1.55−1.47 (m, 4H),
1.37−1.31 (m, 2H); 13C NMR (125 MHz, CDCl3), δ 191.3, 184.2,
140.5, 131.0, 130.2, 128.1, 41.7, 31.7, 24.8, 24.0; IR (CHCl3, cm-1) ν
1674, 1587; LC-MS (APCI) m/z [M + H]+ Calcd for C14H16ClO2S
283.0, found 283.0; HRMS (ESI) m/z [M + H]+ Calcd for
C14H16ClO2S 283.0554, found 283.0562.
S-Cyclohexyl 2-(4-Methoxyphenyl)-2-oxoethanethioate 4e. Yel-
low gummy solid, yield: 91 mg (56%); 1H NMR (400 MHz, CDCl3) δ
8.13 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 3.87
(s, 3H), 3.69−3.64 (m, 1H), 2.02−1.99 (m, 2H), 1.78−1.75 (m, 2H),
1.52−1.44 (m, 4H), 1.33−1.29 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 193.3, 185.1, 164.9, 133.3, 124.5, 114.2, 55.6, 42.5, 32.8,
25.9, 25.9; IR (CHCl3, cm−1) ν 1672, 1596; LC-MS (APCI) m/z [M +
H]+ Calcd for C15H19O3S 279.0, found 279.0; HRMS (ESI) m/z [M +
H]+ Calcd for C15H19O3S 279.1049, found 279.1054.
S-Cyclohexyl 2-(3,4-Dimethylphenyl)-2-oxoethanethioate 4f. Yel-
low gummy solid, yield: 93 mg (58%); 1H NMR (400 MHz, CDCl3) δ
7.86 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.23 (s, 1H), 3.71 (m, 1H), 2.33
(s, 3H), 2.31 (s, 3H), 2.02−2.00 (m, 2H), 1.75−1.73 (m, 2H), 1.52−
1.44 (m, 4H), 1.37−1.29 (m, 2H); 13C NMR (125 MHz, CDCl3) δ
193.1, 186.7, 144.9, 137.3, 131.5, 130.0, 129.4, 128.6, 42.6, 32.8, 25.9,
25.4, 20.3, 19.7; IR (CHCl3, cm−1) ν 1664, 1599; LC-MS (APCI) m/z
S-Pentyl 2-Oxo-2-(p-tolyl)ethanethioate 4k. Yellow gummy solid,
1
yield: 85 mg (58%); H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0
Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 3.05 (t, J = 7.6 Hz, 2H), 2.43 (s,
3H), 1.72−1.65 (m, 2H), 1.43−1.33 (m, 4H), 0.93 (t, J = 6.4 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 193.3, 186.1, 146.1, 130.8, 129.5,
129.1, 31.0, 28.85, 28.83, 22.1, 21.9, 13.9; IR (CHCl3, cm−1) ν 1679,
1606; LC-MS (APCI) m/z [M + H]+ Calcd for C14H19O2S 251.0,
found 251.0; HRMS (ESI) m/z [M + H]+ Calcd for C14H19O2S
251.1100, found 251.1112.
S-Hexyl 2-Oxo-2-(p-tolyl)ethanethioate 4l. Yellow gummy solid,
1
yield: 96 mg (62%); H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0
Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 3.05 (t, J = 7.6 Hz, 2H), 2.43 (s,
3H), 1.71 (m, 2H), 1.44 (m, 2H), 1.33 (m, 4H), 0.91 (t, J = 6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 193.3, 186.1, 146.1, 130.8,
129.5, 129.1, 31.2, 29.1, 28.8, 28.5, 22.5, 21.9,14.0; IR (CHCl3, cm−1)
ν 1679, 1606; LC-MS (APCI) m/z [M + H]+ Calcd for C15H21O2S
265.0, found 265.0; HRMS (ESI) m/z [M + H]+ Calcd for C15H21O2S
265.1257, found 265.1262.
S-Octyl 2-Oxo-2-(p-tolyl)ethanethioate 4m. Yellow gummy solid,
yield: 110 mg (64%); 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0
Hz, 2H), 7.30 (d, J = 7.6 Hz, 2H), 3.05 (t, J = 7.6 Hz, 2H), 2.43 (s,
3H), 1.69 (m, 2H), 1.44 (m, 2H), 1.29 (m, 12H), 0.89 (t, J = 7.2 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 193.3, 186.1, 146.1, 130.89,
130.88, 129.58, 129.56, 31.78, 31.76, 29.14, 29.12, 29.07, 29.05, 28.8,
22.64, 22.62, 14.1, 14.07, 14.06; IR (CHCl3, cm−1) ν 1679, 1606; LC-
MS (APCI) m/z [M + H]+ Calcd for C17H25O2S 293.0, found 293.0;
HRMS (ESI) m/z [M + H]+ Calcd for C17H25O2S 293.1570, found
293.1578.
S-Cyclohexyl 2-(3,4-Dimethoxyphenyl)-2-oxoethanethioate 4n.
Yellow gummy solid, yield: 81 mg (45%); 1H NMR (400 MHz,
CDCl3) δ 7.78 (dd, J = 1.6, 6.8 Hz, 1H), 7.57 (s, 1H), 6.85 (d, J = 6.8,
D
J. Org. Chem. XXXX, XXX, XXX−XXX