New method for the synthesis of pyrroles [1]

Full text of DOI:10.1023/A:1019529717407

Chemistry of Heterocyclic Compounds, Vol. 38, No. 5, 2002
LETTERS TO THE EDITOR
NEW METHOD FOR THE
SYNTHESIS OF PYRROLES
S. A. Vizer, E. Kh. Dedeshko, and K. B. Erzhanov
Keywords: 1-acetyl-3-butynyl methyl ketone, 3-acetyl-2,5-dimethylpyrrole, cyclization.
NH-Pyrroles have been prepared from esters of α-amino-β-keto acids and ketones (Knorr synthesis),
from 1,4-diketones and ammonia by the reaction of β-keto acids with ammonia and a chlorinated ketone
(Hantsch method) [1], by the heterocyclization of ketoximes with acetylene (Trofimov reaction), and by the
reaction of ketoximes with vinyl halides, with 1,2-dichloroethane, or 1,2-dibromoethane [2].
We are the first to report that 3-acyl-2,5-dimethylpyrrole (2) may be obtained by the reaction of 1-acyl-
3-butynyl methyl ketone (1) with ammonium chloride in aqueous ethanol at 50-60°C catalyzed by freshly
prepared Cu2Cl2 with continuous air bubbling and heating.
Me
O
O
O
Me
NH4Cl
CH2
CH
C
Cu2Cl2, O2
EtOH, H2O
Me
Me
CH
N
H
Me
Me
1
2
H
O
C
CH2
CH2
C
CH
+
H2N
H2N
Me
Me
4
3
The greatest yield of pyrrole 2 (49%) was achieved using a three-fold excess of Cu2Cl2 and 10-fold
1
excess of NH4Cl. Pyrrole 2, whose structure was confirmed by elemental analysis, IR and H NMR
spectroscopy, is a rather stable compound, which darkens upon exposure to light. This compound may be stored
for a long period in a refrigerator in the dark but undergoes partial decomposition to an enamine and the starting
ketone upon chromatography on silica gel.
The reaction of 1 with ammonia in aqueous ethanol at 50-60°C leads to the formation of only a 4:1
mixture of enamines 3 and 4. Pyrrole 2 is also not formed in the reaction of diketone 1 with NH4Cl in aqueous
ethanol taking CuCl2 as the catalyst.
__________________________________________________________________________________________
A. B. Bekturov Institute of Chemical Sciences, Ministry of Education and Science of the Republic of
Kazakhstan, 480100 Almaty, Kazakhstan; e-mail: vizer@astel.kz. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 5, pp. 702-203, May, 2002. Original article submitted March 13, 2001.
616
0009-3122/02/3805-0616$27.00©2002 Plenum Publishing Corporation

1-Acetyl-3-butynyl Methyl Ketone (1) was obtained from acetylacetone and propargyl bromide [3].
3-Acetyl-2,5-dimethylpyrrole (2). A solution of diketone 1 (1.32 g, 0.01 mol) in ethanol (15 ml) was
added with vigorous stirring and air bubbling to a solution of NH4Cl (5.35 g, 0.1 mol) and freshly prepared
Cu2Cl2 (2.97 g, 0.03 mol) in water (25 ml). The mixture was heated at 50-60°C for 2 h. After cooling, a
saturated solution of NaCl and aqueous ammonia were added. The mixture was extracted with benzene. The
benzene solvent was distilled off. The residue was subjected to chromatography on a column packed with
Silpearl silica gel (d 40 mm, h 130 mm) using 10:1 benzene–acetone and then 10:2 benzene–acetone as the
eluent to give 0.67 g (49%) pyrrole 2 as a light orange powder; mp 81-82°C, Rf 0.69 (on Silufol UV-254 with
5:1 benzene–acetone as the eluent). IR spectrum in KBr pellet, ν, cm-1: 1360, 1376, 1448, 1524, 1592 (C=C–N
1
pyrrole), 1620 (C=O), 3160 (N–H). H NMR spectrum (CDCl3), δ, ppm: 2.18 (3H, s, 5-CH3); 2.36 (3H, s,
2-CH3); 2.48 (3H, s, –C(O)–CH3); 6.14 (1H, s, 4-H); 9.21 (1H, s, N–H). Found: m/z 137 [M]+. Calculated:
M 137. Found, %: C 70.01; H 8.54. C8H11NO. Calculated, %: C 70.04; H 8.08.
REFERENCES
1.
2.
Chemical Handbook [in Russian], Khimiya, Leningrad (1975).
B. A. Trofimov and A. I. Mikhaleva, N-Vinylpyrroles [in Russian], Nauka (Siberian Branch),
Novosibirsk (1984).
3.
J. Houben, Methods in Organic Synthesis [Russian translation], ONTI, Moscow (1935), Vol. 3(2),
p. 439.
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