Preparation of Sulfonylureas from N,N′-Sulfuryldiimidazoles
cooled at 0 °C was slowly added a solution of sulfuryl chloride
t, J ) 6.2 Hz), 3.83 (2 H, t, J ) 6.2 Hz), 4.70 (3 H, s), 4.88 (2
H, s), 7.15-7.24 (4 H, m), 7.70 (1 H, s), 8.06 (1 H, s), 9.62 (1
H, s). IR (KBr): 3144, 3120, 3081, 1644, 1583, 1528, 1457,
2 2
(8.2 mL, 102 mmol) in CH Cl (45 mL). The reaction was
warmed to room temperature and stirred overnight. The
mixture was concentrated, and the resulting solid was recrys-
tallized from isopropyl alcohol. The crystals were filtered and
washed with cold isopropyl alcohol and dried under high
-
1
1416, 1281, 1197, 1161, 1122, 1094, 1077, 1033 cm . Anal.
Calcd for C14 : C, 39.34; H, 3.77; N, 9.83. Found:
C, 39.15; H, 3.57; N, 9.56.
16 3 3 5 2
H F N O S
vacuum to give 3b (9.8 g, 42%) as a white crystalline solid.
Typ ica l P r oced u r e for th e P r ep a r a tion of Su lfon yl-
u r ea s Exem p lified by 3,4-Dih yd r o-1H-isoqu in olin e-2-
su lfon ic Acid P h en yla m id e (7a ). A solution of triflate salt
6a (175 mg, 0.41 mmol) and aniline (38 mg, 0.41 mmol) in
MeCN (2 mL) was stirred at 80 °C for 18 h. The reaction
mixture was concentrated under reduced pressure. The residue
was dissolved in EtOAc (20 mL), washed with 1 N HCl, 1 N
NaOH, H O, and saturated NaCl, and dried over Na SO .
1
Mp: 90-91 °C. H NMR (300 MHz, CDCl
3
): δ 2.53 (6 H, s),
6
3
.96 (2 H, d, J ) 1.7 Hz), 7.38 (2 H, d, J ) 1.7 Hz). IR (KBr):
145, 3118, 3005, 1756, 1555, 1422, 1378, 1354, 1267, 1056
-
1
cm . Anal. Calcd for C
Found: C, 42.56; H, 4.54; N, 24.89.
-(Im id a zole-1-su lfon yl)-1-m et h yl-3H -im id a zol-1-iu m
8 10 4 2
H N O S: C, 42.47; H, 4.45; N, 24.76.
3
1
2
Tr ifla te (4a ). To a solution of N,N ′-sulfuryldiimidazole 3a
5.95 g, 30.0 mmol) in CH Cl (120 mL) at 0 °C was added
dropwise 4 mL (30.0 mmol) of methyl triflate over a period of
0 min. After 3 h at 0 °C, the solid was filtered and dried under
high vacuum to give triflate salt 4a (10.19 g, 94%) as a white
2
2
4
(
2
2
Purification by silica gel chromatography (hexanes/EtOAc 9:1)
1
gave 7a (110 mg, 94%) as a white solid. Mp: 104-105 °C. H
1
NMR (300 MHz, CDCl ): δ 2.82 (2 H, t, J ) 5.9 Hz), 3.57 (2
3
1
3
H, t, J ) 5.9 Hz), 4.51 (2 H, s), 7.02-7.29 (9 H, m). C NMR
(75 MHz, CDCl ): δ 28.83, 44.25, 47.65, 120.40, 124.69, 126.35,
1
solid. Mp: 85 °C dec. H NMR (300 MHz, CD
3
OD): δ 4.01 (3
3
H, s), 7.21 (1 H, s), 7.85-7.88 (2 H, m), 8.38 (1 H, t, J ) 2.1
Hz), 8.51 (1 H, s), 10.05 (1 H, s). IR (KBr): 3144, 3120, 3081,
126.42, 126.82, 128.93, 129.38, 131.85, 133.33, 137.15. IR
(KBr): 3271, 2896, 2836, 1603, 1487, 1423, 1353, 1320, 1147,
-
1
1
1
538, 1528, 1457, 1416, 1281, 1197, 1161, 1122, 1094, 1077,
15 16 2 2
1073, 1024 cm . Anal. Calcd for C H N O S: C, 62.48; H,
-
1
033 cm . Anal. Calcd for C
8
H
9
F
3
N
4
O
5
S
2
: C, 26.52; H, 2.50;
5.59; N, 9.71. Found: C, 62.42; H, 5.63; N, 9.65.
N, 15.46. Found: C, 26.23; H, 2.62; N, 15.18.
-(Im id a zole-1-su lfon yl)-1,2,3,4-t et r a h yd r oisoq u in o-
lin e (5a ). To a solution of triflate salt (4a ) (2.5 g, 6.9 mmol)
2
Ack n ow led gm en t . We thank Professor Henry
Rapoport for the many chemistry discussions from
which this paper is inspired and Dr. Kerry Spear and
Dr. Brian Marron for their assistance in the manuscript
preparation.
in MeCN (27 mL) was added 1,2,3,4-tetrahydroisoquinoline
(576 µL, 4.6 mmol). After being stirred at room temperature
overnight, the reaction mixture was concentrated and the
residue purified using FC on silica gel (1:1 hexane/ethyl
acetate) to give 5a (675 mg, 56%) as a tan solid. Mp: 118-
1
Note Ad d ed a fter ASAP P ostin g. The table of
contents graphic had an incorrect structure in the version
posted November 23, 2002; the correct version was posted
December 4, 2002.
1
19 °C. H NMR (300 MHz, CDCl
3
): δ 2.93 (2 H, t, J ) 6.1
Hz), 3.55 (2 H, t, J ) 6.1 Hz), 4.43 (2 H, s), 7.04-7.21 (6 H,
m), 7.99 (1 H, s). IR (KBr): 3145, 3121, 3081, 1583, 1528, 1416,
1
281, 1224, 1197, 1161, 1123, 1094, 1078, 1033 cm-1. Anal.
Calcd for C12
C, 54.79; H, 5.02; N, 16.17.
-(3-Meth yl-im idazole-1-su lfon yl)-1,2,3,4-tetr ah ydr oiso-
qu in olin e Tr ifla te (6a ). To a solution of isoquinoline 5a (1.11
g, 4.22 mmol) in CH Cl (14 mL) cooled at 0 °C was added
.52 mL (4.63 mmol) of methyl triflate. After being stirred for
h at 0 °C, the reaction mixture was concentrated under
13 3 2
H N O S: C, 54.74; H, 4.98; N, 15.96. Found:
Su p p or tin g In for m a tion Ava ila ble: Full characteriza-
tion for compounds 4b, 5b, 6b, 7b-m , 8a -g, 9a -e, 16a -d ,
2
1
H NMR spectra for compounds 1-9e and 16a -d , and LC/
2
2
MS traces of the crude reaction for the preparation of 9a ,d ,x
and 16d using 6a . This material is available free of charge
via the Internet at http://pubs.acs.org.
0
2
reduced pressure to give 6a (1.80 g, 100%) as a beige solid.
1
Mp: 111-113 °C. H NMR (300 MHz, CD
3
OD): δ 3.00 (2 H,
J O026505K
J . Org. Chem, Vol. 68, No. 1, 2003 119