Phase-transfer catalyzed alkylation of morpholine with 1,2-dichloroethane

Full text of DOI:10.1134/S1070363212020302

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 2, pp. 344–345. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.J. Markosyan, G.A. Baghdasaryan, G.P. Oganesyan, A.O. Attaryan, G.V. Asratyan, 2012, published in Zhurnal Obshchei Khimii,
2012, Vol. 82, No. 2, pp. 349–350.
LETTERS
TO THE EDITOR
Phase-Transfer Catalyzed Alkylation of Morpholine
with 1,2-Dichloroethane
A. J. Markosyana, G. A. Baghdasaryanb, G. P. Oganesyanb,
A. O. Attaryana, and G. V. Asratyanb
a Institute of Organic Chemistry, of Scientific Technological Centre of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, Azatutyan ave. 26, Yerevan, 0014 Armenia
b Armenian Institute of Applied Chemistry “ARIAC,” Artashat ave. 5/2, Yerevan, 0053 Armenia
e-mail: baghdasaryangayane@rambler.ru
Received July 5, 2011
DOI: 10.1134/S1070363212020302
Piperazine was found to react with 1,2-dichloro-
ethane to give first 1-(2-chloroethyl)piperazine, and
then 3-azonio-6-azospiro[2,5]octane chloride as con-
Our studies on the alkylation of morpholine I with
1,2-dichloroethane showed that the course of this
simple reaction depends on the sequence of the
reagents addition. Thus, when the reagents were added
simultaneously, the alkylation of morpholine I with
1,2-dichloroethane (molar ratio 1:10) results in 1,2-
bismorpholinoethane III in 70% yield. In this case 1-
(2-chloroethyl)morpholine II was not detected in the
reaction mixture. When morpholine was added drop-
wise within several hours at the same reagents ratio the
reaction products were 1-(2-chloroethyl)morpholine II
and 1,2-bismorpholinoethane III (2:1).
1
firmed by experimental data and H, 13C, 15N spec-
troscopy [1]. The 3-azonio-6-azospiro[2,5]octane chlo-
ride reacts with piperazine to form dipiperazinyl-
ethane. This suggests that it would not be possible to
direct the reaction toward the production of the mono-
substituted product while suppressing the formation of
the disubstituted product. This is also observed in the
case of the reaction of 1,2-dichloroethylene with mor-
pholine in aqueous alkaline medium in the presence of
triethylbenzylammonium chloride (TEBACH) to give
1,2-bismorpholinoethylene in 65.5% yield [2].
Based on these data, we can assume that the
reaction of 1-(2-chloroethyl)morpholine II with
morpholine I occurs as a direct nucleophilic substitu-
tion of the chlorine atom by the SN1 mechanism [3],
but not through the formation of an intermediate
compound IV [1, 4].
Aiming at the synthesis of 1-(2-chloroethyl)mor-
pholine II, in the present work we carried out the
alkylation of morpholine I with dichloroethane in a
liquid-liquid system in the presence of triethyl-
benzylammonium chloride as a phase-transfer catalyst.
Cl−
ClCH2CH2Cl
+
O
NH
O
O
N CH2CH2Cl
N
I
II
IV
I
I
O
O
CH2 N
N CH2
344
III

PHASE-TRANSFER CATALYZED ALKYLATION OF MORPHOLINE
345
1-(2-Chloroethyl)morpholine (II). Into a three-
neck flask equipped with a thermometer, a reflux
condenser, and a mechanical stirrer were placed 1 mol
of dichloroethane, 0.5 mol of NaOH in 25 ml of water,
and 2 g of TEBACH. To the mixture 0.05 mol of
morpholine was added dropwise with vigorous stirring.
The reaction mixture was stirred at 70–80°C for 2.5 h.
After cooling, to the reaction mixture was added the
second portion of alkali (0.5 mol of NaOH in 25 ml of
water) and 0.05 mol of morpholine. The stirring was
continued at 70–80°C for 2.5 h. Then the reaction
mixture was cooled, extracted with chloroform, dried
over magnesium sulfate, concentrated, and distilled in
a vacuum. Yield 4.5 g (30%), bp 65°C (2 mm Hg), nD20
roethane and 1 mol of the base. Yield 7 g (70%), bp
110°C (3 mm Hg), mp 63–64°C (hexane). IR spec-
1
trum, ν, cm–1: 1100 (CH2–O–CH2). Н NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 2.38 m [8H, N(CH2)4],
2.40 s [4H, N(CH2)2], 3.56 m [8H, O(CH2)4]. Found,
%: C 59.12; H 9.24; N 13.65. C10H20N2O2. Calculated,
%: C 60.00, H 10.00, N 14.00.
The NMR spectra were registered on a Varian
Mercury-300 spectrometer (300 MHz) in DMSO-d6 or
CDCl3 solution. The IR spectra were obtained on a
Specord 75-IR instrument (thin layer).
REFERENCES
1
1.4789. IR spectrum, ν, cm–1: 1100 (CH2–O–CH2). Н
1. Borisenko, V.S., Bobylev, V.A., and Tereshchenko, G.F.,
NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.50 m
[4H, N(CH2)2], 2.70 t (2H, NCH2, J 7.9), 3.54 t (2H,
CH2Cl, J 7.0), 3.68 m [4H, O(CH2)2]. Found, %: C
47.25; H 7.66; N 9.00; Cl 24.46. C6H12ClNO.
Caclulated, %: C 47.84; H 7.97; N 9.30; Cl 24.25.
Yield of 1,2-bismorpholinoethane III is 2.2 g (22%).
Zh. Obshch. Khim., 1988, vol. 58, no. 1, p. 206.
2. Khachikyan, R. Dzh., Davtyan, S.L., and Indzhi-
kyan, M.G., Khim. Zh. Arm., 2006, vol. 59, no. 1, p. 93.
3. Ingold, K., Teoreticheskiye osnovy organicheskoi khimii
(Theoretical Bases of Organic Chemistry), Moscow:
Mir, 1973, p. 1054.
1,2-Bismorpholinoethane (III) was prepared
similarly from 8.7 g of morpholine I, 1 mol of dichlo-
4. Leonard, N.J. and Paukstelis, J.V., J. Org. Chem., 1965,
vol. 30, p. 821.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012