H. Veisi, R. Azadbakht, M. Ezadifar, and S. Hemmati
Vol 000
Scheme 1. Synthesis of pyrroles from g-diketones and primary amines
using sodium dodecyl sulfate (SDS) in water.
(80%) when the reaction was performed at 100°C in the
presence of SDS. It is found that this condensation reac-
tion gave 3a in moderate yield (50%) under solvent-free
conditions due to the solubility of p-toluenesulfonylhy-
drazide in γ-diketones, and the yields showed significant
improvement with increasing of temperature. In another
case, we changed γ-diketones and the N-(2,5-diphenyl-
1H-pyrrol-1-yl)-4-methylbenzenesulfonamide (3b) was
obtained with decrease of yield (55%), which is most
probably due to the electron-donating and steric effects
of the phenyl groups.
O
SDS
+
RNH2
N
R
3
Water, r.t.
O
1
2
R: alkyl and aryl
RESULTS AND DISCUSSION
In our continued interest in the development of a highly
expedient methodology [24] for the synthesis of fine che-
micals and heterocyclic compounds of biological impor-
tance, we report here a simple and efficient method for
the synthesis of N-substituted pyrroles from reaction of
γ-diketones and primary amines in aqueous micellar media,
using sodium dodecyl sulfate (SDS), which simultaneously
functions as a catalyst to promote the reactions and as a
surfactant to assist in solubilizing the organic substrates
(Scheme 1). SDS was chosen since it forms micelles in water,
can solubilize organic compounds, and has been used
successfully in a number of organic reactions as a catalyst.
We started this synthesis by examining the reaction of
hexan-2,5-dione (1 mmol) with benzylamine (1 mmol)
for the synthesis of 2,5-dimethyl-N-benzylpyrrole as a
model reaction. As shown in Table 1, the use of SDS
allowed the direct synthesis of 2,5-dimethyl-N-benzylpyr-
role in a yield of 98% in water (5 mL) at 25°C (Table 1,
Entry 2). The use of more than 10 mol % of SDS did not
enhance chemical yield.
The catalytic effect of micellar SDS in this reaction can be
explained as follows. In the micellar solution, γ-diketones
and primary amines, which are both hydrophobic, are forced
inside the hydrophobic core of the micelles, thus allowing
the reaction to take place more easily (Fig. 1).
These results promoted us to investigate the scope and
generality of this new protocol for various amines (aliphatic
and aromatic) under optimized conditions. In the same man-
ner, a variety of amines were coupled with hexan-2,5-dione
in the presence of SDS at room temperature to give the
corresponding pyrroles in good to excellent yields (Table 1).
The less basic aromatic amines require only slightly more
time than the more basic amino compounds, and both lead
to high yields of the pyrrole products.
CONCLUSIONS
In summary, a practical and convenient synthetic method
in aqueous media using SDS as the surfactant catalyst
(10 mol %) has been developed for the facile synthesis of
N-substituted pyrroles. The advantages of the method in-
clude (i) absence of organic solvent, (ii) short reaction times,
(iii) high yields, (iv) easy work-up, and furthermore, this pro-
cedure is cheap, safe, and environmentally benign.
EXPERIMENTAL
All commercially available chemicals were obtained from
Merck and Fluka companies, and used without further purifica-
tions unless otherwise stated. 1H-NMR spectra were recorded
on a Jeol 90 MHz FT-NMR spectrometer using tetramethylsilane
as internal standard and chemical shift are in δ (ppm). Infrared
(IR) was conducted on a Perkin-Elmer GX FTIR spectrometer.
All yields refer to isolated products.
General procedure for the synthesis of pyrroles in
the presence of SDS. The amine
1 (1 mmol) and 2,
5-hexanedione 2 (1 mmol) were added to a solution of SDS
(10 mol %, 0.03 g) in H2O (5 mL), and the mixture stirred at
room temperature for the time given (Table 1). The progress of the
reaction was monitored by TLC (eluent: 7:3 n-hexane-acetone).
After completion of the reaction, K2CO3 (0.5 mmol, 0.07 g) was
added to the reaction mixture, and the resulting precipitate of
dodecyl sulfate filtered off. The filtrate was extracted with ethyl
acetate (4 × 10 mL), dried over anhydrous MgSO4, and evaporated
to give analytically pure product. When necessary, further
purification was achieved by thin layer chromatography using
n-hexane/acetone (70:30) as the solvent system to afford the
pyrroles. The spectral and analytical data of some representative
compounds are given below.
Analytical data for selected compounds. Compound
The reaction conditions were also applicable to diamino
or triamino substrates, in giving bipyrrole (Table 1, Entries
4, 11–13, 15, 19, and 20) or tripyrrole compounds (Table 1,
Entry 21) in excellent yields.
Finally, we examined the condensation reactions of
γ-diketones with p-toluenesulfonylhydrazide in the
presence of SDS as catalyst and surfactant in water
(Scheme 2). N-(2,5-Dimethyl-1H-pyrrol-1-yl)-4-methyl-
benzenesulfonamide (3a) was obtained with good yields
(4).
Cream solid, mp 197–198°C; IR (KBr): νmax 1515,
1462, 1410, 1377, 1303, 1019 cm−1
;
1H-NMR (CDCl3, FT-
250 MHz): δ 2.13 (s, CH3, 12H), 4.97 (s, CH2, 4H), 5.84
(s, pyrrolics, 4H), 6.82 (s, PhH, 4H); Found: M+ 292.1939.
C20H24N2 requires M, 292.1946; Anal. Calcd for
C20H24N2.0.5 H2O: C, 78.29; H, 8.54; N, 9.96. Found: C,
79.88; H, 8.16; N, 8.97.
Compound (10). Pale yellow solid, mp 174–175°C; IR
(nujol): νmax 2400–2200, 1678, 1607, 1463, 1377, 1324, 1129,
1106 cm−1 1H-NMR (CDCl3, FT-250 MHz): δ 2.00 (s, CH3,
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet