H4), 6.56-6.58 (1H, m, H3), 6.92-6.94 (1H, m, H5), 8.67 (1H,
d, J 10, ArH), 8.72 (1H, dd, J 10, 2, ArH), 8.92 (1H, br s, NH),
9.03 (1H, d, J 2, ArH); δC(CDCl3) 111.0 (C4), 113.0 (C3), 120.9,
123.1 (C5), 127.4, 129.3, 127.2, 145.1, 147.2, 151.1; δC (DMSO-
d6) 109.8, 113.6, 121.2, 124.4, 128.7, 130.0, 130.2, 145.2, 149.1,
149.6; m/z 281 (M+, 100), 82 (23).
with the observation that oxidation of 10 to give 11
proceeds readily but that oxidation of 6 to give 7 proceeds
extremely sluggishly.
2-(2,4-Dinitrobenzenesulfonyl)pyrrole (7). To glacial ace-
tic acid (10 mL) at 40 °C was added 2-(2,4-dinitrobenzenesulfe-
nyl)pyrrole (6) (100 mg, 0.377 mmol). After 10 min, 30%
hydrogen peroxide (0.500 mL, 4.41 mmol) was added to the
reaction flask. The reaction mixture was stirred for 27 h and
then poured into distilled water, followed by the addition of satd
NaHCO3. The aqueous reaction mixture was then washed twice
with ethyl acetate. The combined organic layers were dried over
MgSO4, and then the solvent was removed in vacuo to yield the
crude product as an oily yellow residue. Careful crystallization
from CH2Cl2 and hexanes gave the title product as a bright
yellow crystalline solid (8 mg, 7%): mp 132-134 °C; Rf (1:19
EtOAc/hexanes) 0.24; δH (CDCl3) 6.38-6.40 (1H, m, H4), 7.08-
7.10 (1H, m, H3), 7.16-7.18 (1H, m, H5), 8.45 (1H, d, J 10),
8.52-8.55 (2 H, m), 9.49 (1H, br s, NH); δC (CDCl3) 112.0 (C4),
119.4 (C3), 120.2, 125.3 (C2), 126.2 (C5), 127.2, 132.8, 141.3,
148.7, 150.2; m/z 297 (M+, 100), 82 (53) (found M+, 297.0064,
C10H7N3SO6 requires 297.0055).
2-(4-Nitrobenzenesulfenyl)pyrrole (9). Following the pro-
cedure for the preparation of 2-(2,4-dinitrobenzenesulfenyl)-
pyrrole (5), the title compound (57%) was prepared as a yellow
crystalline solid from pyrrole and 2-(4-nitrobenzene)sulfenyl
chloride: mp 76-77 °C; Rf (1:1 hexanes/CH2Cl2) 0.24; δH (CDCl3)
6.38-6.40 (1H, m, H4), 6.61-6.63 (1H, m, H3), 7.01 (1H, d, J
10), 7.04-7.06 (1H, m, H5), 7.99 (1H, d, J 10), 8.37 (1H, br s,
NH); δC (CDCl3) 111.3 (C4), 112.7 (C2), 119.9 (C3), 123.2 (C5),
124.2, 125.1, 145.4, 149.9; m/z EI+ 220 (M+, trace); m/z APCI+
221 (MH+, 100), 205 (16).
2-(4-Nitrobenzenesulfinyl)pyrrole (10). Following the pro-
cedure for the preparation of 2-(2,4-dinitrobenzenesulfinyl)-
pyrrole, the title compound (88%) was prepared as a light yellow
crystalline solid from 2-(4-nitrobenzenesulfenyl)pyrrole: mp 154
°C; Rf (1:1 EtOAc/CH2Cl2) 0.17; δH (CDCl3) 6.32-6.33 (1H, m,
H4), 6.78-6.80 (1H, m, H3), 7.02-7.04 (1H, m, H5), 7.81 (1H,
d, J 10), 8.36 (1H, d, J 10), 9.42 (1H, br s, NH); δC (CDCl3) 110.2
(C4), 115.9 (C3), 124.2, 125.2 (C5), 125.9, 128.2 (C2), 149.4, 151.2;
m/z APCI+ 237 (MH+, 100), 220 (37).
2-(4-Nitrobenzenesulfonyl)pyrrole (11). Following the
procedure for the preparation of 2-(2,4-dinitrobenzenesulfinyl)-
pyrrole, the title compound (84%) was prepared as a very pale
yellow crystalline solid from 2-(4-nitrobenzenesulfenyl)pyrrole
and excess m-CPBA: mp 271-272 °C; Rf (1:1 EtOAc/CH2Cl2)
0.90; δH (CDCl3) 6.40-6.42 (1H, m, H4), 6.99-7.01 (1H, m, H3),
7.09-7.11 (1H, m, H5), 8.12 (1H, d, J 10), 8.36 (1H, d, J 10),
9.15 (1H, br s, NH); δC (CDCl3) 112.3 (C4), 117.2 (C3), 124.7,
124.8 (C5), 126.6 (C2), 128.2, 148.3, 150.3; m/z APCI+ 253 (100),
156 (18).
This research shows that alternative protecting groups
to carboxylates may be considered for pyrroles, thus
expanding the synthetic scope of pyrrole chemistry. Our
proof-of-principle studies show that 2,4-dinitrobenzene-
sulfinyl and sulfonyl groups are sufficiently electron-
withdrawing to effectively stabilize pyrroles and that they
may be efficiently removed using thiols and thiolates. The
mononitrobenzenesulfinyl and sulfonyl pyrroles also
stabilize the pyrrole ring, but deprotection of these
functional groups is accompanied by reduction. Our
research is now focusing on the efficient synthesis, from
acyclic materials, of functionalized pyrroles with 2,4-
dinitrobenzenesulfonyl protecting groups in the 2-position
and assessing the robustness of these functionalized
pyrroles.
Experimental Section
Dimethyl(2-pyrrolyl)sulfonium chloride and 2-(methylthio)-
pyrrole were prepared as previously reported.28 2-(Methylsulfi-
nyl)pyrrole21 was prepared according to the method used by
Carmona et al.27 for the synthesis of 2-(butylsulfinyl)pyrrole.
2-(Methylsulfonyl)pyrrole21 was prepared from 2-(methylthio)-
pyrrole according to the method used by Beveridge and Harris45
for the synthesis of 2-(2-nitrobenzenesulfonyl)pyrrole.
2-(2,4-Dinitrobenzenesulfenyl)pyrrole (5).26 Freshly dis-
tilled pyrrole (4.0 mL, 57.7 mmol) was added to a solution of
2-(2,4-dinitrobenzene)sulfenyl chloride (12.91 g, 55.0 mmol) in
dry CH2Cl2 (500 mL), under nitrogen. The reaction mixture was
stirred for 16 h at room temperature and then the solvent
removed in vacuo. The crude product was then purified by
column chromatography (dry-loaded) eluting with 2:3 CH2Cl2/
hexanes, followed by crystallization from CH2Cl2 and hexanes,
giving the title compound as a yellow crystalline solid (10.2 g,
70%): mp 149-150 °C; Rf (4:1 CH2Cl2/hexanes) 0.37; δH (CDCl3)
6.44-6.48 (1H, m, H4), 6.70-6.74 (1H, m, H3), 6.92 (1H, d, J
10, ArH), 7.34-7.39 (1H, m, H5), 8.29 (1H, dd, J 10, 2, ArH),
8.45 (1H, br s, NH), 9.15 (1H, d, J 2, ArH); δC (CDCl3) 111.8
(C4), 112.2 (C2), 120.8 (C3), 121.3, 127.2, 124.0 (C5), 128.9, 143.7,
144.7, 149.2; m/z 265 (M+, 12), 82 (100) (found M+, 265.0142,
Acknowledgment. This work was supported by
Dalhousie University and The Natural Sciences and
Engineering Research Council of Canada.
C
10H7N3SO4 requires 265.0157).
2-(2,4-Dinitrobenzenesulfinyl)pyrrole (6). 2-(2,4-Dini-
trobenzenesulfenyl)pyrrole (5) (2.0 g, 7.5 mmol) was dissolved
in CH2Cl2. A solution of 50% m-CPBA (2.85 g, 8.25 mmol) was
added and the reaction mixture stirred for 2 h. The precipitate
was then filtered off and purified by column chromatography
(dry loaded) eluting with 1:49 MeOH/CH2Cl2 to give the title
compound as green/yellow solid (1.20 g, 57%): mp 157-158 °C
dec; Rf (1:19 MeOH/CH2Cl2) 0.24; δH (CDCl3) 6.21-6.23 (1H, m,
Supporting Information Available: X-ray crystallo-
graphic data and ORTEP diagrams for 1, 4, 5, and 7. This
material is available free of charge via the Internet at
JO050077B
3756 J. Org. Chem., Vol. 70, No. 9, 2005