J. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 8133–8135
8135
Toluene appears to be the best choice of solvents. This
reaction proceeded smoothly in commercial toluene
IV; (b) Leonid, I.; Belen, K. Heterocycles 1994, 37,
2029–2049; (c) Reinecke, M. G.; Johnson, H. M.; Sebas-
tian, J. F. J. Am. Chem. Soc. 1963, 85, 2859–2860.
9. (a) Yadav, J. S.; Srinivas, D.; Reddy, G. S.; Bindu, K.
H. Tetrahedron Lett. 1997, 38, 8745–8748; (b) Yadav, J.
S.; Reddy, B. V. S.; Reddy, G. S. K. K. Tetrahedron
Lett. 2000, 41, 2695–2697; (c) Kumar, H. M. S.;
Anjeneyulu, S.; Reddy, B. V. S.; Yadav, J. S. Synlett
1999, 551–552; (d) Yadav, J. S.; Reddy, B. V. S.; Reddy,
M. M. Tetrahedron Lett. 2000, 41, 2663–2665; (e)
Yadav, J. S.; Reddy, B. V. S.; Reddy, G. S. K. K. New
J. Chem. 2000, 24, 571–573; (f) Kumar, H. M. S.;
Reddy, B. V. S.; Anjaneyulu, S.; Yadav, J. S. Tetra-
hedron Lett. 1999, 40, 8305–8306.
(
containing 0.1% water) but the attempted reaction in
water alone was not successful. All products were
characterized by H NMR, IR and mass spectroscopic
1
data and also by comparison with known 2-acyl sub-
8
stituted pyrrole derivatives. The reactions were clean
and complete within 1–3 h. Among the various metals
such as zinc, indium, samarium, and yttrium studied
for this transformation, zinc was found to be more
10
effective in terms of selectivity and conversion. This
method is equally effective for the sulfonation of
pyrrole with sulfonyl chlorides to afford the corre-
sponding 2-sulfonyl pyrroles (entries b, c, g, Table 1).
The scope and generality of this process is illustrated
with respect to various acid chlorides, sulfonyl chlo-
rides and N-substituted pyrrole derivatives and the
results are summarized in the Table 1.
1
0. General procedure: A mixture of pyrrole (5 mmol), acid
chloride (7.5 mmol), zinc powder (10 mmol) in toluene
(
10 mL) was stirred at room temperature for the appro-
priate time (Table 1). After completion of the reaction
as indicated by TLC, the reaction mixture was quenched
with saturated sodium bicarbonate solution (15 mL) and
extracted with ethyl acetate (2×15 mL). Evaporation of
the solvent followed by purification on silica gel (Merck,
In summary, we have demonstrated a novel and highly
efficient method for the acylation and sulfonation of
pyrrole and its derivatives using zinc metal under mild
and neutral reaction conditions. The method offers
several advantages including high yields of products,
cleaner reaction profiles, greater regioselectivity, and
simple experimental/product isolation procedures,
which make it a useful and attractive strategy for the
acylation and sulfonation of pyrrole and its derivatives
of synthetic importance.
100–200 mesh, ethyl acetate/hexane, 0.5–9.5) afforded
the pure 2-acyl pyrrole derivative.
Spectroscopic data for selected products: 3a: Solid, mp
1
1
18°C, H NMR (200 MHz, CDCl ) l: 1.34 (s, 3H),
3
1.42 (s, 3H), 2.32 (dd, 1H, J=8.1, 8.5 Hz), 2.78 (d, 1H,
J=8.1 Hz), 6.29 (dd, 1H, J=2.5, 3.7 Hz), 6.90 (dd, 1H,
J=2.9, 3.7 Hz), 7.0 (d, 1H, J=2.9 Hz), 7.20 (d, 1H,
J=8.5 Hz), 10.40 (brs, NH, 1H).
13
C NMR (CDCl , proton decoupled, 50 MHz) l: 14.7,
3
Acknowledgements
2
1
1
2
3
8.6, 30.9, 33.1, 37.0, 110.7, 116.5, 123.2, 124.9, 130.7,
30.8, 133.4, 186.5. IR (KBr) w: 3285, 3089, 1622, 1416,
−
1
+
295, 1108, 963, 777 cm . EI MS: m/z: 291 M , 258,
B.V.S., G.K., R.S.R. thank CSIR, New Delhi for the
award of fellowships.
00, 179, 95, 66, 39.
1
c: H NMR (200 MHz, CDCl ) l: 2.40 (s, 3H), 6.18
3
(
6
(
dd, 1H, J=2.5, 3.7 Hz), 6.75 (dd, 1H, J=2.9, 3.7 Hz),
.90 (d, 1H, J=2.9 Hz), 7.20 (d, 2H, J=8.0 Hz), 7.80
d, 2H, J=8.0 Hz), 11.80 (brs, NH, 1H).
IR (KBr) w: 3324, 1578, 1445, 1380, 1296, 1226, 1141,
References
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6
784–6786; (b) Liu, C. M.; Hermann, T. E.; Liu, M.;
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(
3
m, 2H), 2.80 (t, 2H, J=6.7 Hz), 6.20 (dd, 1H, J=2.7,
.7 Hz), 6.80 (dd, 1H, J=2.7, 3.5 Hz), 7.0 (d, 1H,
2
13
J=2.7 Hz), 9.40 (brs, NH, 1H). C NMR (CDCl3,
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2
3
(b) Silverstein, R. M.; Ryskiewiez, E. E.; Willard, C.;
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−
1
+
cm . EI MS: m/z: 305 M , 122, 109, 94, 43, 36.
3
6
Hz), 7.10 (dd, 1H, J=8.0, 2.1 Hz), 7.15 (d, 1H, J=2.7
Hz), 7.30 (d, 1H J=8.0 Hz), 7.40 (d, 1H, J=2.1 Hz),
7
NMR (CDCl , proton decoupled, 50 MHz) l: 55.3,
1
1
j: Liquid, H NMR (200 MHz, CDCl ) l: 3.80 (s, 3H),
4
3
.24 (dd, 1H, J=2.7, 3.7 Hz), 6.80 (dd, 1H, J=2.7, 3.5
2
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6
. Beon, G. P. J. Heterocycl. Chem. 1965, 2, 473–474.
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13
.50 (dd, 1H, J=8.0, 2.1 Hz), 10.6 (brs, NH, 1H).
C
3
10.9, 113.6, 118.0, 119.7, 121.5, 125.6, 129.2, 131.0,
7
8
. Kozikowski, A. P.; Ames, A. J. Am. Chem. Soc. 1980,
1
02, 860–862.
139.6, 159.4, 184.6. IR (KBr) w: 3276, 1604, 1577, 1420,
1395, 1252, 1041, 913, 771 cm . EI MS: m/z: 201 M ,
186, 170, 158, 135, 130, 107, 94, 66, 39.
−
1
+
. (a) Livingstone, R. In Rodd’s Chemistry of Carbon Com-
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