Mechanochemical Activation of the Reaction of Tetraacetylglycoluril with Some Cyclic Primary Amines. Synthesis of Acetamides

Article abstract of DOI:10.1134/S1070428018040292

A new mechanochemical method has been proposed for the synthesis of some acetamides containing a cyclic fragment by reaction of primary cyclic amines with tetraacetylglycoluril.

Full text of DOI:10.1134/S1070428018040292

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 4, pp. 668–669. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © A.A. Bakibaev, N.F. Khoang, V.V. Mamontov, 2018, published in Zhurnal Organicheskoi Khimii, 2018, Vol. 54, No. 4, pp. 663–664.
SHORT
COMMUNICATIONS
Mechanochemical Activation of the Reaction of
Tetraacetylglycoluril with Some Cyclic Primary Amines.
Synthesis of Acetamides
A. A. Bakibaeva,* N. F. Khoangb, and V. V. Mamontovb
a Tomsk National Research State University, pr. Lenina 36, Tomsk, 634050 Russia
*e-mail: bakibaev@mail.ru
b Tomsk National Research Polytechnic University, pr. Lenina 30, Tomsk, 634050 Russia
Received May 10, 2017
Abstract—A new mechanochemical method has been proposed for the synthesis of some acetamides con-
taining a cyclic fragment by reaction of primary cyclic amines with tetraacetylglycoluril.
DOI: 10.1134/S1070428018040292
Derivatives of bicyclic bisureas are polyfunctional
compounds that have found wide application in vari-
ous fields of human activity (disinfecting agents, medi-
cines, components of explosives, etc.) [1, 2]. Among
these, a particular position is occupied by N-acetyl
derivatives, some of which are efficient bleaching
activators for detergents [3]. The main methods of
synthesis of N-substituted bicyclic bis-ureas have been
reviewed in [4, 5].
73% of acetanilide (3a) in 90 h; this procedure is less
efficient than the mechanochemical synthesis because
of long reaction time. Acetamides 3a–3d were also
prepared independently by acylation of the correspond-
ing amines with acetic anhydride; the products ob-
tained by the two methods were identical, and their
properties were in agreement with published data.
2-Amino-5-chlorobenzhydrol, 5-chloro-2-methyl-
aminobenzhydrol, 5-aminosalicylic acid, anthranilic
acid, and 5-aminoquinoline failed to undergo acetyla-
tion with glycoluril 2 under mechanochemical activa-
There are limited published data on the use of the
parent N-acetylated bicyclic bisurea, tetraacetylglyco-
luril 2, as acetylating agent in the synthesis of proteins
[6] and acylamines [7], and these data are scanty and
non-systematic. Mechanochemical synthesis provides
a convenient method for the preparation of organic
compounds [8, 9]. However, the behavior of N-acyl
derivatives of bicyclic bisureas toward amines under
mechanochemical activation has not been studied
previously.
O
O
Me
O
Me
O
H
N
N
N
Me
R
2
2 RNH2
+
N
N
O
Me
Me
O
O
1a–1e
2
3a–3e
Taking into account the above stated, we were the
first to accomplish mechanochemical reactions of
some primary amines 1a–1e with tetraacetylglycoluril
2. Simple grinding of a mixture of amine 1a–1e and
bisurea 2 in a porcelain mortar for 5 min at room tem-
perature afforded 74–90% of the corresponding acet-
amides 3a–3c and 3e; in the synthesis of compound 3d
from 4-aminoantipirine 1d, the reaction mixture was
heated for 1 h at 110°C, and the yield of 3d was as low
as 33%. According to [10], the reaction of 2 with
aniline (1a) in chloroform at room temperature yields
O
Me
O
H
N
N
+
O
N
N
H
Me
O
4
R = Ph (a), PhCH2 (b), cyclohexyl (c), 1,5-dimethyl-3-oxo-
2-phenyl-2,3-dihydro-1H-pyrazol-4-yl (d), 4-phenyl-4,5-di-
hydro-1,3-thiazol-2-yl (e).
668

MECHANOCHEMICAL ACTIVATION
669
Table 1. Conditions of synthesis, yields, melting points, and 1H NMR data of compounds 3a–3e
Reaction Temperature,
Product
(yield, %)
1H NMR spectrum,
Initial amine
mp, °C
time, min
°C
δNH, ppm
Aniline (1a)
05
05
05
60
20
025
005
025
110
150
3a (74)
3b (81)
3c (79)
3d (33)
3e (90)
116–117
60–62
07.94
07.78
05.98
09.09
12.24
Benzylamine (1b)
Cyclohexylamine (1c)
103–105
197–201
206–208
4-Aminoantipyrine (1d)
4-Phenyl-4,5-dihydro-1,3-thiazol-2-amine (1e)
tion. In these cases, compound 2 was converted to
diacetylglycoluril 4, as reported previously for the
reaction of 2 with diamines [11]. The reaction of di-
acetylglycoluril 4 with aniline under mechanochemical
activation gave only traces of acetanilide (3a).
zene, 1:4), following the disappearance of the initial
amine; spots were visualized by treatment with
Ehrlich’s reagent.
REFERENCES
The reaction of 2 with benzylamine (1b) was
accompanied by vigorous evolution of heat, so that it
was necessary to cool the reaction mixture to 5°C
(Table 1); obviously, this is related to the high basicity
of amine 1b compared to other amines. Poor solubility
of diacetylglycoluril 4 provides an additional advan-
tage to the mechanochemical procedure of synthesis of
acetamides 3a–3d which can be readily extracted with
an appropriate solvent. Diacetylglycoluril 4 isolated
from the reaction mixture can be used to regenerate
tetraacetyl derivative 2 according to [12], and the latter
can be reused.
1. Bakibaev, A.A., Yagovkin, A.Yu., and Vostretsov, S.N.,
Russ. Chem. Rev., 1998, vol. 67, p. 295.
2. Petersen, H., Synthesis, 1973, p. 243.
3. Zavel’skaya, V.D. and Zamchuk, Z.S., Prikladnaya
khimiya: Obzornaya informatsiya (Applied Chemistry.
Review Data), Moscow: NIITEKhIM, 1988, p. 1.
4. Bakibaev, A.A., Yagovkin, A.Yu., and Korol’ko-
va, S.M., Izv. Vyssh. Uchebn. Zaved., Khim. Khim.
Tekhnol., 2000, vol. 43, no. 3, p. 43.
5. Kravchenko, A.N. and Chikunov, I.E., Russ. Chem.
Rev., 2006, vol. 75, p. 191.
6. Kuhling, D., Justus Liebigs Ann. Chem., 1973, p. 263.
Acetylanilide (3a). A mixture of 2 mL (22 mmol)
of aniline (1a) and 1.55 g (5 mmol) of tetraacetyl-
glycoluril 2 was ground in a porcelain mortar for 5 min
at 25°C. The mixture was treated with 25 mL of
ethanol, the undissolved material was filtered off, and
the filtrate was evaporated to give 1 g (74%) of 3a.
7. Hase, Ch. and Kuhling, D., Justus Liebigs Ann. Chem.,
1975, p. 95.
8. Wang, G.W., Chem. Soc. Rev., 2013, vol. 42, p. 7668.
9. James, S.L. and Friscic, T., Chem. Soc. Rev., 2013,
vol. 42, p. 7494.
10. Kuhling, D. and Hase, Ch., FRG Patent Appl.
no. 2220690, 1973.
Acetamides 3b–3e were synthesized in a similar
way; the reaction temperatures, times, and yields are
given in Table 1.
11. Vladimir, M.S.A. and Sindelar, V., Tetrahedron, 2011,
vol. 67, p. 8937.
12. Bakibaev, A.A., Mamaeva, E.A., Yanovskii, V.A., Bys-
tritskii, E.L., and Yagovkin, A.Yu., Preparativnye
metody sinteza azotsoderzhashchikh soedinenii na
osnove mochevin (Preparative Methods of Synthesis of
Nitrogen-Containing Compounds on the Basis of
Ureas), Tomsk: Agraf-Press, 2007, p. 124.
1
The H NMR spectra were recorded on a Bruker
Avance III HD spectrometer at 400 MHz using
DMSO-d6 as solvent and tetramethylsilane as internal
standard. The progress of reactions was monitored by
TLC on Silufol UV-254 plates (eluent ethanol–ben-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 4 2018