Functionalization of p-Tolylsulfonamides
J . Org. Chem., Vol. 66, No. 11, 2001 3667
M), precooled to 0 °C under an Ar atmosphere, was treated
dropwise with n-BuLi in hexanes (2.2 equiv). The resulting
bright yellow solution was stirred at 0 °C for 30 min prior to
quenching with the appropriate electrophile (1.2 equiv, unless
otherwise stated). Following stirring at 0 °C for 1 h, the
reaction mixture was quenched with a satd aq NH4Cl solution
(5 mL), and the reaction mixture was extracted with Et2O (3
× 5 mL). The ether extract was dried (Na2SO4), subjected to
filtration, and concentrated, and the resulting residue was
purified by flash column chromatography (EtOAc/hexanes).
2-Deu ter o-N-eth yl-4-m eth ylben zen esu lfon a m id e (5a ).
Use of the general procedure with the following materials [1
(0.1056 g, 0.53 mmol), n-BuLi (0.43 mL, 2.70 M, 1.2 mmol),
and CD3OD (0.22 mL, 5.4 mmol, precooled to 0 °C) in THF (5
mL)], followed by flash column chromatography (20% EtOAc/
hexanes) afforded 5a as a colorless oil (0.0996 g, 94%); 1H NMR
(300 MHz, CDCl3) 7.75 (d, J ) 8.4 Hz, 1H), 7.32-7.30 (m, 2H),
4.39 (bs, 1H), 3.05-2.96 (m, 2H), 2.43 (s, 3H), 1.10 (t, J ) 7.2
Hz, 3H); 2H NMR (61 MHz, CH2Cl2) 7.76 (s); 13C NMR (75
MHz, CDCl3) 143.2, 136.8, 129.6, 129.4, 127.0, 126.7 (t, J )
24.7 Hz), 38.1, 21.4, 14.8; IR (cm-1) 3261, 1324, 1174; MS (EI)
(m/e) 200 (M+, 2), 185 (24), 156 (50), 92 (100); HRMS calculated
for C9DH12NSO2 200.0730, found 200.0731.
column chromatography (20% EtOAc/hexanes) afforded 5e
(0.5801 g, 78%) as a light yellow solid. Recrystallization from
CH2Cl2/hexanes afforded 5e as fine colorless crystals; mp 71.0-
73.0 °C (CH2Cl2/hexanes); 1H NMR (300 MHz, CDCl3) 8.04 (d,
J ) 8.0 Hz, 1H), 7.89 (s, 1H), 7.28 (dd, J ) 2.0, 8.2 Hz, 1H),
5.14 (s, 1H), 2.98-2.89 (m, 2H), 2.37 (s, 3H), 1.11 (t, J ) 7.2
Hz, 3H); 13C NMR (75 MHz, CDCl3) 144.4, 142.6, 138.9, 131.2,
129.2, 92.1, 38.2, 20.7, 14.9; IR (cm-1) 3304, 1630, 1585, 1314,
1154; MS (EI) (m/e) 325 (M+, 63), 310 (82), 281 (97), 217 (100),
155 (22), 118 (34), 110 (20), 104 (29); HRMS calculated for
C9H12NSO2I 324.9634, found 324.9639.
Syn th eses of N,N-Dieth yl-2-su bstitu ted -4-tolylsu lfon a -
m id es (6). Gen er a l P r oced u r e. A solution of 2 in THF (0.1
M), precooled to -78 °C under Ar atmosphere, was treated
dropwise with n-BuLi in hexanes (1.2 equiv). The resulting
bright yellow solution was stirred at -78 °C for 30 min, unless
otherwise stated, prior to quenching with the appropriate
electrophile (1.1-1.2 equiv). Following stirring at -78 °C for
1 h, the reaction mixture was quenched with a satd aq NH4Cl
solution (5 mL), and the aqueous layer was extracted with CH2-
Cl2 (3 × 5 mL). The ether extract was dried (Na2SO4), subjected
to filtration, and concentrated, and the residue was purified
by flash column chromatography (EtOAc/hexanes or CH2Cl2/
hexanes).
N -E t h y l-4-m e t h y l-2-t r im e t h y ls ily lb e n ze n e s u lfo n -
a m id e (5b). Use of the general procedure with the following
materials [1 (1.01 g, 5.07 mmol), n-BuLi (4.36 mL, 2.56 M,
11.2 mmol), and TMSCl (2.57 mL, 20.2 mmol) in THF (50 mL)],
followed by flash column chromatography (10% EtOAc/hex-
anes) afforded 5b (1.32 g, 96%) as a colorless oil; 1H NMR (300
MHz, CDCl3) 7.84 (d, J ) 8.1 Hz, 1H), 7.56 (d, J ) 1.1 Hz,
1H), 7.31 (dd, J ) 1.1, 8.1 Hz, 1H), 4.43 (t, J ) 5.8 Hz, 1H),
3.04-2.95 (m, 2H), 2.43 (s, 3H), 1.10 (t, J ) 7.2 Hz, 3H), 0.43
(s, 9H); 13C NMR (75 MHz, CDCl3) 142.4, 142.1, 139.8, 137.8,
130.3, 129.0, 38.6, 22.0, 15.5, 1.5; IR (cm-1) 3292, 1424, S1321,
1160; MS (FAB) (m/e) 272 (MH+, 100), 256 (16); HRMS
2-Deu t er o-N,N-d iet h yl-4-m et h ylb en zen esu lfon a m id e
(6a ). Using the general procedure with the following materials
[2 (0.1021 g, 0.45 mmol), n-BuLi (0.22 mL, 2.50 M, 0.55 mmol),
and CD3OD (0.18 mL, 4.4 mmol, precooled to 0 °C) in THF (5
mL)] and the following modification [metalation at -78 °C for
40 s], followed by flash column chromatography (20% EtOAc/
hexanes) afforded 6a as a light yellow solid (0.1024 g, >99%).
Recrystallization from EtOH/H2O gave 6a as colorless
1
needles: mp 40.5-41.0 °C (EtOH/H2O); H NMR (300 MHz,
CDCl3) 7.69 (d, J ) 8.4 Hz, 1H), 7.30-7.27 (m, 2H), 3.22 (q, J
) 7.1 Hz, 4H), 2.42 (s, 3H), 1.12 (t, J ) 7.1 Hz, 6H); 13C NMR
(75 MHz, CDCl3) 142.8, 137.1, 129.5, 129.4, 126.9, 126.6 (t, J
) 25.0 Hz), 41.9, 21.3, 14.0; IR (cm-1) 1636, 1334, 1160; MS
(EI) (m/e) 228 (M+, 6), 213 (63), 156 (93), 92 (100); HRMS
calculated for C11DH16NSO2 228.1060, found 228.1061.
N,N-Dieth yl-4-m eth yl-2-tr im eth ylsilylben zen esu lfon -
a m id e (6b). Using the general procedure with the following
materials [2 (1.0219 g, 4.50 mmol), n-BuLi (2.02 mL, 2.67 M,
5.39 mmol), and TMSCl (1.14 mL, 8.98 mmol) in THF (40 mL)]
and the following modification [metalation at -78 °C for 1 h],
followed by flash column chromatography (50% CH2Cl2/hex-
calculated for
256.0857.
C
11H18NSO2Si (M+ - 15) 256.0844, found
N-Eth yl-2,4-d im eth ylben zen esu lfon a m id e (5c). Using
the general procedure with the following materials [1 (0.1084
g, 0.54 mmol), n-BuLi (0.46 mL, 2.58 M, 1.2 mmol), and MeI
(0.04 mL, 0.6 mmol) in THF (5 mL)], followed by flash column
chromatography (20% EtOAc/hexanes) afforded 5c (0.1055 g,
92%) as a light yellow oil; 1H NMR (300 MHz, CDCl3) 7.86 (d,
J ) 8.4 Hz, 1H), 7.12-7.10 (m, 2H), 4.37 (bs, 1H), 3.03-2.94
(m, 2H), 2.61 (s, 3H), 2.37 (s, 3H), 1.09 (t, J ) 7.2 Hz, 3H); 13
C
1
NMR (75 MHz, CDCl3) 143.2, 136.8, 134.9, 133.1, 129.6, 126.6,
37.8, 21.1, 20.1, 15.0; IR (cm-1) 3301, 1452, 1421, 1318, 1154,
1062; MS (EI) (m/e) 213 (M+, 5), 198 (4), 169 (22), 105 (100),
91 (18), 77 (51); HRMS calculated for C10H15NSO2 213.0824,
found 213.0821.
anes) afforded 6b (1.1601 g, 86%) as a light yellow liquid; H
NMR (300 MHz, CDCl3) 7.58-7.53 (m, 2H), 7.26 (d, J ) 8.0
Hz, 1H), 3.31 (q, J ) 7.1 Hz, 4H), 2.38 (s, 3H), 1.16 (t, J ) 7.1
Hz, 6H), 0.42 (s, 9H); 13C NMR (75 MHz, CDCl3) 143.2, 140.9,
139.6, 136.8, 129.7, 126.7, 41.7, 21.2, 14.1, 1.0; IR (cm-1) 1321,
1147; MS (EI) (m/e) 299 (M+, 1), 284 (100); HRMS calculated
for C14H25NSO2Si 299.1375, found 299.1378.
N-E t h yl-2-(h yd r oxyp h en ylm et h yl)-4-m et h ylb en zen e-
su lfon a m id e (5d ). Using the general procedure with the
following materials [1 (0.1090 g, 0.55 mmol), n-BuLi (0.47 mL,
2.58 M, 1.2 mmol), and benzaldehyde (0.06 mL, 0.6 mmol) in
THF (5 mL)], followed by flash column chromatography (20%
EtOAc/hexanes) afforded 5d (0.1607 g, 96%) as a light yellow
solid. Recrystallization from EtOAc/hexanes afforded 5d as
colorless crystals; mp 152.5-153.0 °C (EtOAc/hexanes); 1H
NMR (300 MHz, CDCl3) 7.88 (d, J ) 8.0 Hz, 1H), 7.40-7.34
(m, 6H), 7.26-7.22 (m, 1H), 6.57 (s, 1H), 3.62 (bs, 1H-
exchanges with D2O), 3.40 (bs, 1H- exchanges with D2O), 2.67
N,N-Dieth yl-2,4-d im eth ylben zen esu lfon a m id e (6c). Us-
ing the general procedure with the following materials [2
(0.1076 g, 0.47 mmol), n-BuLi (0.23 mL, 2.50 M, 0.58 mmol),
and MeI (0.04 mL, 0.6 mmol) in THF (5 mL)], followed by flash
column chromatography (10% EtOAc/hexanes) afforded 6c
(0.1045 g, 92%) as a colorless liquid; 1H NMR (300 MHz,
CDCl3) 7.80 (d, J ) 8.4 Hz, 1H), 7.10-7.07 (m, 2H), 3.30 (q, J
) 7.1 Hz, 4H), 2.55 (s, 3H), 2.36 (s, 3H), 1.12 (t, J ) 7.1 Hz,
6H); 13C NMR (75 MHz, CDCl3) 142.9, 137.4, 135.3, 133.2,
129.7, 126.4, 40.5, 21.1, 20.1, 13.6; IR (cm-1) 1456, 1378, 1314,
1134; MS (EI) (m/e) 241 (M+, 2), 226 (25), 169 (47), 105 (100);
HRMS calculated for C12H19NO2S 241.1137, found 241.1133.
N,N-Diet h yl-2-(h yd r oxyp h en ylm et h yl)-4-m et h ylb en -
zen esu lfon a m id e (6d ). Using the general procedure with the
following materials [2 (0.1096 g, 0.48 mmol), n-BuLi (0.23 mL,
2.50 M, 0.58 mmol), and benzaldehyde (0.07 mL, 0.7 mmol) in
THF (5 mL)], followed by flash column chromatography (20%
EtOAc/hexanes) afforded 6d (0.1490 g, 93%) as a colorless
(bd, J ) 6.5 Hz, 2H), 2.40 (s, 3H), 0.82 (t, J ) 7.2 Hz, 3H); 13
C
NMR (75 MHz, CDCl3) 143.7, 142.0, 141.5, 133.8, 130.8, 130.3,
128.4, 128.2, 127.7, 126.9, 71.6, 38.0, 21.4, 14.4; IR (cm-1) 3434,
3203, 1293, 1148, 1063; MS (CI) (m/e) 305 (M+, 2), 288 (100);
HRMS calculated for C16H17NSO2 (M+ - H2O) 287.0980, found
287.0972.
N-Eth yl-2-iod o-4-m eth yl-ben zen esu lfon a m id e (5e). Use
of the general procedure with the following materials [1
(0.4585 g, 2.30 mmol), n-BuLi (2.39 mL, 2.02 M, 4.83 mmol),
and I2 (0.6670 g, 2.63 mmol) in THF (5 mL)] and the following
modifications [metalation at 0 °C for 30 min followed by
warming to room temperature and cooling to -78 °C prior to
I2 quench; removal of excess I2 with a satd aqueous solution
of Na2S2O3 (10 mL) prior to NH4Cl quench], followed by flash
1
liquid; H NMR (300 MHz, CDCl3) 7.77 (d, J ) 8.1 Hz, 1H),
7.44-7.30 (m, 5H), 7.17 (d, J ) 8.1 Hz, 1H), 7.05 (s, 1H), 6.68
(s, 1H), 3.45-3.25 (m, 5H), 3.29 (s, 3H), 1.18 (t, J ) 7.2 Hz,
6H); 13C NMR (75 MHz, CDCl3) 143.7, 143.3, 141.8, 135.1,
131.2, 128.9, 128.2, 128.1, 127.1, 126.4, 69.8, 41.1, 21.4, 13.7;