Reactions of Secondary Amines with Dichlorocarbene Generated in Aqueous–Alkaline Medium in the Presence of N-Methylmorpholine N-Oxide

Article abstract of DOI:10.1134/S1070428018060258

Dichlorocarbene generated from chloroform in aqueous–alkaline medium in the presence of N-methylmorpholine N-oxide is converted to phosgene which reacts in situ with secondary amines to afford tetrasubstituted ureas.

Full text of DOI:10.1134/S1070428018060258

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 6, pp. 959–960. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © A.G. Hasratyan, G.A. Bagdasaryan, S.S. Hayotsyan, H.S. Attaryan, 2018, published in Zhurnal Organicheskoi Khimii, 2018,
Vol. 54, No. 6, pp. 951–952.
SHORT
COMMUNICATIONS
Reactions of Secondary Amines with Dichlorocarbene
Generated in Aqueous–Alkaline Medium in the Presence
of N-Methylmorpholine N-Oxide
A. G. Hasratyana, G. A. Bagdasaryana, S. S. Hayotsyana, and H. S. Attaryana*
a Institute of Organic Chemistry, Scientific Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, pr. Azatutyan 26, Yerevan, 0014 Armenia
*e-mail: hovelenatt@mail.ru
Received December 14, 2017
Abstract—Dichlorocarbene generated from chloroform in aqueous–alkaline medium in the presence of
N-methylmorpholine N-oxide is converted to phosgene which reacts in situ with secondary amines to afford
tetrasubstituted ureas.
DOI: 10.1134/S1070428018060258
We have recently proposed a novel medium for the
alkylation of secondary amines, a 50% aqueous solu-
tion of N-methylmorpholine N-oxide (NMMO) [1–3].
In order to explore the scope of application of this
system, we have studied formylation of secondary
amines 1–4 by reaction with dichlorocarbene generated
in the presence of NMMO. It has long been known
[4–6] that insertion of dichlorocarbene into the NH
bond of secondary amines under conditions of phase-
transfer catalysis (PTC) leads to the formation of the
corresponding N,N-dialkylformamides as the major
products.
Unlike PTC conditions [6], dichlorocarbene gen-
erated in aqueous NMMO from chloroform in the pres-
ence of sodium hydroxide reacts with NMMO to give
phosgene. Reaction of the latter with secondary amines
1–4 afforded N,N,N′,N′-tetraalkylureas 5–8 in 25–55%
yield. The structure of 5–8 was confirmed by IR and
1H and 13C NMR spectra and elemental analyses.
zwitterionic intermediate which is converted to phos-
gene while NMMO is reduced to morpholine [7].
Di(morpholin-4-yl)methanone (5). a. A solution
of 20.0 g (0.4 mol) of sodium hydroxide in 30 mL of
water was added dropwise to a mixture of 8.7 g
(0.1 mol) of morpholine, 50 mL of chloroform, and
50 mL of 50% aqueous NMMO, heated to 50°C. The
mixture was stirred for 1 h at 50°C, cooled, and treated
with chloroform, and the extract was evaporated. Yield
3.5 g (35%), mp 143–145°C (from EtOAc); published
data [8]: mp 142.2°C. IR spectrum: ν 1643 cm–1
1
(C=O). H NMR spectrum, δ, ppm: 3.14–3.19 m (8H,
CH2), 3.55–3.69 m (8H, CH2). 13C NMR spectrum,
δC, ppm: 46.60, 65.66, 162.38.
b. Following an analogous procedure, from 8.7 g
(0.1 mol) of morpholine, 50 mL of chloroform, and
50 mL of 70% aqueous NMMO we obtained 5.5 g
(55%) of 5 with mp 144–145°C.
Compounds 6–8 were synthesized in a similar way.
Di(piperidin-1-yl)methanone (6) was synthesized
A probable reaction mechanism involves addition
of dichlorocarbene to the N-oxide oxygen atom to give
from 8.5 g (0.1 mol) of piperidine. Yield 2.2 g (22%),
PTC
R2NCHO
O
CHCl3, NaOH
R2NH
NMMO
1–4
R2N
NR2
5–8
1, 5, R2N = morpholin-4-yl; 2, 6, R2N = piperidin-1-yl; 3, 7, R = Me; 4, 8, R = Et; NMMO stands for N-methylmorpholine N-oxide.
959

HASRATYAN et al.
960
bp 130°C (1 mm), n2D0 = 1.5000; published data:
bp 120–122°C (0.02 mm) [9], nD28 = 1.5055 [10]. IR
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 6 2018