Unexpected formation of 2,4,6-triphenylpyridine in the synthesis of 2,5-diphenyl-pyrrole from acetophenone oxime and phenylacetylene

Full text of DOI:10.1007/s10593-009-0345-0

Chemistry of Heterocyclic Compounds, Vol. 45, No. 7, 2009
UNEXPECTED FORMATION OF
2,4,6-TRIPHENYLPYRIDINE IN
THE SYNTHESIS OF 2,5-DIPHENYL-
PYRROLE FROM ACETOPHENONE
OXIME AND PHENYLACETYLENE
E. Yu. Schmidt1, N. V. Zorina1, I. A. Ushakov1, E. V. Skital'tseva1,
A. I. Mikhaleva1, and B. A. Trofimov1*
Keywords: acetophenone oxime, 2,5-diphenylpyrrole, 2,4,6-triphenylpyridine, phenylacetylene.
The synthesis of 2,5-diphenylpyrrole (1) [1, 2] (in special cases, 2,4-diphenylpyrrole [3]) from
acetophenone oxime 2 and phenylacetylene in MOH–DMSO superbase systems (M = Li, Na, K) by means of
the Trofimov reaction has gained preparative significance despite low yields of the desired product because the
pyrrole obtained is a promising chemical intermediate. Further optimization of this synthesis will involve
determining the structure of the sideproducts as well as reducing both the number and amount of such
side-products. However, at present, we only know that a significant amount of acetophenone 3 [1] is formed
during the reaction. In essence, acetophenone 3 is not a sideproduct since it may be reused after oximation in the
same synthesis. Other components of the reaction mixture have not yet been identified.
In a study of this reaction in the 1:1 molar ratio LiOH–DMSO system at 130°C for 5 h, we unexpectedly
isolated 2,4,6-triphenylpyridine (4) in 2.5% yield along with the expected 2,5-diphenylpyrrole 1 and
acetophenone 3.
p"
m"
o"
i"
Ph
4
Ph
Me
Ph
O
3
2
5
+
+
Ph
Ph
N
OH
N
H
Me
6
LiOH–DMSO
130C, 5 °h
N
2
3
i'
i
o
1
p
o'
p'
m
m'
4
_______
* To whom correspondence should be addressed, e-mail: boris_trofimov@irioch.irk.ru.
1A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, Irkutsk
664033, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1089-1091, July, 2009. Original
article submitted April 29, 2009.
868
0009-3122/09/4507-0868©2009 Springer Science+Business Media, Inc.

Intermediate O-vinyl oxime 5 rearranges to give nitrone 6 [4], which then condenses with
acetophenone 3 to give trienic nitrone 7. The electrocyclization of 7 leads to dihydropyridine N-oxide 8, which
rearranges to give N-hydroxydihydropyridine 9. The 1,4-elimination of methanol through 1,4-diradical 10 (an
analog of the 1,4-benzoid Bergman diradical [5, 6]) leads to pyridine 4. Examples of the aromatization of
dihydropyridines with the loss of methanol have been reported by Nedolya et al. [7, 8].
The formation of pyridine 4 may be shown by the following scheme:
Ph
Ph
Me
O
Ph
Me
Ph
Me
Ph
Me
–
N
N
Ph
N
Ph
O
Ph
B
O
6
5
O
7
Ph
Ph
Ph
Me
Ph
Me
.
.
.
.
OH
CH3
Ph
N
Ph
Ph
N
Ph
N
O
Ph
Ph
Ph
N
Ph
MeOH
.
}
OH
10
8
4
9
This reaction expands the basic chemistry of oximes and acetylenes and may stimulate further synthetic
investigations.
1
The H, 13C, and 13N NMR spectra were taken on a Bruker 400DPX spectrometer at 400, 100, and
40 MHz, respectively, in CDCl3 with HMDS (δ 0.05 ppm) as the internal standard. The IR spectra were taken on
a Bruker ISF-25 spectrometer. The mass spectrum was taken on a Shimadzu QP5050-A mass spectrometer.
Synthesis of 2,5-Diphenylpyrrole (1), Acetophenone (3) and 2,4,6-triphenylpyridine (4). A mixture
of acetophenone oxime 2 (5.00 g, 37 mmol) and phenylacetylene (4.16 g, 42 mmol) was dissolved in DMSO
(50 ml) and LiOH (0.88 g, 37 mmol) was added. The mixture was heated for 5 h at 130°C and then cooled.
Water (100 ml) was added and the mixture was extracted with five 25 ml ether portions. The ethereal extracts
were washed with water and dried over K2CO3. After removal of the ether, the residue was subjected to
chromatography on an alumina column using gradient elution from hexane to 1:1 hexane–ether to give 1.08 g
(13.3%) 2,5-diphenylpyrrole 1, 1.24 g (28.0%) acetophenone 3, and 0.28 g (2.5%) pyridine 4.
2,4,6-Triphenylpyridine (4) was obtained as pale-yellow crystals, mp 132-134°C (hexane,
1
135-136°C [9]). IR spectrum (KBr), ν, cm-1: 1594, 1550, 1527, 1494, 1398, 1361, 865, 757, 692. H NMR
spectrum, δ, ppm (J, Hz): 8.20 (4H, m, H-o'); 7.88 (2H, s, H-3, H-5); 7.74 (2H, m, H-o"); 7.54-7.43 (9H, m,
H-m', H-p', H-m", H-p"). 13C NMR spectrum, δ, ppm: 157.59 (C-2, C-6); 150.27 (C-4); 139.68 (C-i, C-i');
139.17 (C-i"); 129.18, 129.10, 129.04, 128.99, (C-p", C-p', C-p, 2C-m"); 128.77 (2C-m', 2C-m); 127.36, 127.26,
15
127.20 (2C-o", 2C-o', 2C-o); 117.18 (C-3, C-5). N NMR spectrum, δ, ppm: -83 (N-1). Mass spectrum, m/z:
307. Found, %: C 89.79; H 5.55; N 4.58. C23H17N. Calculated, %: C 89.87; H 5.57; N 4.56.
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