ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 10, pp. 1571−1572. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © N.N. Yusubov, V.M. Ismailov, Z.A. Mamedova, 2007, Vol. 43, No. 10, pp. 1573−1574.
SHORT
COMMUNICATIONS
Synthesis and Transformations of γ-Chlorobutanoic Acid
Phenyl(ethyl)amide
N. N. Yusubov, V. M. Ismailov, and Z. A. Mamedova
Baku State University, Baku, AZ-1148, Azerbajdzhan
e-mail: niftali-yusubov@rambler.ru
Received October 11, 2006
DOI: 10.1134/S1070428007100314
Trimethylenecarbonyl fragment is a structural base
of many biologically active compounds [1, 2]. A con-
venient synthon for introducing this fragment is γ-chloro-
butyryl chloride. It was previously established [3, 4] that
alkoxybenzenes acylation with γ-chlorobutyryl chloride
Et
Et
N CO(CH2)3Cl
N C
O
Na
III
led to the formation of heterocyclic compounds
.
γ-Chlorobutyric acid N-ethyl-N-phenylamide (I).
To 24.0 g (0.2 mol) of N-ethylaniline in 100 ml of ether
at cooling (0°C) while stirring was gradually added
14.51 g (0.1 mol) of γ-chlorobutyryl chloride. The mix-
ture was stirred for 2 h, then it was treated with water
and extracted with ether. The ether extract was dried with
Na2SO4, ether was distilled off, the residue was distilled
in a vacuum. Yield 14 g (62%), bp 125°C (0.05 mm Hg),
In this study we investigated the acylation of N-ethyl-
aniline with γ-chlorobutyryl chloride that proceeded with
the formation of the corresponding N-acylated product,
γ-chlorobutyric acid ethylphenylamide (I).
Et
N CO(CH2)3Cl
NHEt
ClCO(CH2)3Cl
Ether, 0oC
d240 1.0990, n20 1.5386. MRD 64.21, calc. 64.24. H NMR
1
spectrum, δ,Dppm: 1.0 t (3H, CH3), 1.2 m (2H, CCH2C),
1.97 m (2H, CH2CO), 3.4 q (2H, NCH2), 3.5 t (2H,
CH2Cl), 7.25 m (5H, C6H5). Found, %: Cl 15.52; N 6.08.
C12H16ClNO. Calculated, %: Cl 15.74; N 6.20.
I
In the presence of alkaline and acidic catalysts amide
I suffered a number of interesting transformations. The
boiling of compound I in hexane in the presence ofAlCl3
resulted in intramolecular alkylation into the ortho-
position of the aromatic ring giving a bicyclic compound
1-ethyl-2,3-benzazepin-7-one (II).
1-Ethyl-2,3-benzazepin-7-one (II). To 4.50 g (0.02 mol)
of amide I in 50 ml of heptane at cooling while stirring
was gradually added 7.98 g (0.06 mol) of AlCl3. The
mixture was heated for 2 h at 60–70°C. On cooling the
mixture was poured on a mixture of 100 g of ice and
10 ml of concn. HCl, the reaction product was extracted
into heptane, and the extract was dried over Na2SO4.
Yield 1.0 g (26%), bp 135°C (0.03 mm Hg), d240 1.0701,
Et
O
N
nD20 1.5428. MRD 55.63, calc. 55.76. H NMR spectrum,
1
AlCl3
I
δ, ppm: 1.0 t and 3.5 q (5H, N–Et), 2.2 m (2H, CH2Ph),
1.1 m (2H, CCH2C), 2.6 m (CH2CO), 6.8–7.0 m
(4H,C6H5). Found, %: C 75.95; N 7.13. C12H15NO.
Calculated, %: C 76.19; N 7.60.
II
In the presence of sodium metal amide I is alkylated
yielding a cyclopropane derivative, N-ethyl-N-phenyl-
cyclopropylamide (III).
N-Ethyl-N-phenylcyclopropylamide (III). A mix-
ture of finely dispersed sodium metal and 4.5 g (0.02 mol)
1571
Yusubov
