N-haloalkylation reaction in the presence of trichloroacetic acid

Full text of DOI:10.1007/s11178-006-0028-6

Russian Journal of Organic Chemistry, Vol. 41, No. 11, 2005, pp. 1716−1717. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 11, 2005,
pp. 1750−1751.
Original Russian Text Copyright  2005 by Kurbanova.
SHORT
COMMUNICATIONS
N-Haloalkylation Reaction in the Presence
of Trichloroacetic Acid
M.M. Kurbanova
Baku State University, Baku, AZ-1073 Azerbaidzhan
e-mail: kurbanova1972@rambler.ru
Received November 11, 2004
N-Substituted ureas, thioureas, and related compounds
find applications in industry, engineering, agriculture, and
medicine, therefore the interest of researchers is still
attracted by the synthesis of these substances.
The reaction progress was monitored by TLC follow-
ing the disappearance of the initial substrate.
The results of the study show that application of
trichloroacetic acid instead of sulfuric acid prevents
sulfonation and oxidation processes in the course of the
synthesis of N-substituted compounds.
We formerly investigated the nucleophilic substitution
of a hydroxy group in alkoxy- and alkylthio-substituted
1,2-chlorohydrins by weak N-nucleophiles, like urea and
thiourea, in the presence of trifluoroacetic acid [1, 2] and
in a mixture of sulfuric and acetic acids [3]. From these
reactions resulted various alkoxy- and alkylthio-substituted
carbamides and thiocarbamides.
N-(2-Chloroethyl)piperidine (I). A solution of 3.4
g (0.04 mol) of piperidine, and 3.22 g (0.04 mol) of
ethylenechlorohydrin in 9 ml of trichloroacetic acid was
stirred with a magnetic stirrer at room temperature for
2 h. On completion of the reaction the excess tri-
chloroacetic acid was distilled off in a vacuum, the residue
was treated with water and chloroform. The organic
phase was washed with water, dried over Na2SO4, and
the solvent was distilled off. The product was purified by
recrystallization from a mixture hexane–ethyl acetate,
3:1. Yield 65%, mp 189–190°C. IR spectrum, ν, cm–1:
690 (C–Cl). 1H NMR spectrum, δ, ppm: 1.6–1.9 m (6H,
3CH2), 2.9 m (4H, 2CH2), 3.2 t (2H, N–CH2), 3.7 t (2H,
CH2Cl). 13C NMR spectrum, δ, ppm: 54.78 (CH2), 24.56
(CH2), 23.12 (CH2), 58.97 (NCH2), 40.93 (CH2Cl).
Found, %: C 57.01; H 9.52; Cl 24.15; N 9.48.
C7H14ClN. Calculated, %: C 56.94; H 9.49; Cl 24.06;
N 9.49.
The practical value of N-alkylation reactions used
nowadays is limited by the requirement to perform them
in the concentrated mineral acids. The processes of this
type in the presence of trichloroacetic acid were not
described in the literature.
It turned out that the piperidine, a stronger base than
urea, reacted with ethylene chlorohydrin in the presence
of trichloroacetic acid affording in a 65% yield N-(2-
chloroethyl)piperidine (I).
CCl3COOH
NCH2CH2Cl
NH + HOCH2CH2Cl
I
N-(2-Chloroethyl)urea (II). A solution of 2.4 g
(0.04 mol) of urea, and 3.22 g (0.04 mol) of ethylene
chlorohydrin in 9 ml of trichloroacetic acid was stirred
with a magnetic stirrer at 50–60°C for 6 h.On completion
of the reaction the excess trichloroacetic acid was distilled
off in a vacuum, the residue was treated with water and
chloroform. The organic phase was washed with water,
dried over Na2SO4, and the solvent was distilled off. The
product was purified by recrystallization from a mixture
hexane–ethyl acetate, 1:1. Yield 60%, mp 206–207°C.
With the less nucleophilic urea the reaction occurred
at heating to 50–60°C giving N-(2-chloro-ethyl)urea (II)
in a 60%C yield.
NH2CNH2 + HOCH2CH2Cl
O
CCl3COOH
NH2CNHCH2CH2Cl
O
II
1070-4280/05/4111-17162005 Pleiades Publishing, Inc.

N-HALOALKYLATION REACTION
1717
IR spectrum, ν, cm–1: 3490 (NH2), 3340 (NH), 1635
REFERENCES
(C=O), 700 (C–Cl). 1H NMR spectrum, δ, ppm: 6.85 s
(1H, NH), 5.75 s (2H, NH2), 3.5 t (2H, N–CH2), 3.9 t
(2H, CH2–Cl). Found, %: C 29.44; H 5.69; Cl 29.01;
N 22.81. C3H7ClN2O. Calculated, %: C 29.38; H 5.71;
Cl 28.97; N 22.85.
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and Allakhverdiev, M.A., 10th IUPAC International
Symposium on Macromolecule−Metal Complexes, 2003,
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3. Abdinbekova, R.T., Zamanova, A.V., Akhmedova, Kh.A.,
Kurbanov, A.V., Kurbanova, M.M., Magerramov, A.M., and
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1H and 13C NMR spectra from solutions in DMSO-
d6 were registered on spectrometer Bruker-300 (300
ΜHz) at 25°C. IR spectra were recorded on
spectrophotometer Specord 75IR from mulls in mineral
oil. The reaction progress was monitored and the purity
of compounds obtained was checked by TLC on Silufol
UV-254 plates.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005