Functionally substituted isocyanurates with heteroatoms (O, S) in the N-alkyl chain

Article abstract of DOI:10.1023/A:1013281230316

Alkylation of disodium benzyl and disodium methyl isocyanurates with β,β′-dichlorodiethyl and β,β′-dibromodiethyl ethers was used to prepare 1-benzyl and 1-methyl 3,5-bis[2-(2-haloethoxy)ethyl] isocyanurates whose reaction with thiourea followed by hydrol

Full text of DOI:10.1023/A:1013281230316

Russian Journal of General Chemistry, Vol. 71, No. 8, 2001, pp. 1261 1265. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 8, 2001,
pp. 1335 1338.
Original Russian Text Copyright
2001 by Fattakhov, Shulaeva, Reznik.
Functionally Substituted Isocyanurates with Heteroatoms (O, S)
in the N-Alkyl Chain
S. G. Fattakhov, M. M. Shulaeva, and V. S. Reznik
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center,
Russian Academy of Sciences, Kazan, Tatarstan, Russia
Received May 4, 2000
Abstract Alkylation of disodium benzyl and disodium methyl isocyanurates with , -dichlorodiethyl and
, -dibromodiethyl ethers was used to prepare 1-benzyl and 1-methyl 3,5-bis[2-(2-haloethoxy)ethyl] iso-
cyanurates whose reaction with thiourea followed by hydrolysis gave the corresponding 1-alkyl 3,5-bis[2-
(2-mercaptoethoxy)ethyl] isocyanurates. 1-Benzyl and 1-methyl 3,5-bis[2-(2-chloroethyl)ethyl] isocyanurates
were reacted with NaSCH2CH2OH to obtain the corresponding 1-alkyl 3,5-bis[2-(2-hydroxyethylthio)ethyl]
isocyanurates. Treatment of the latter two esters with thionyl chloride gave 1-benzyl and 1-methyl 3,5-bis-
[2-(2-chloroethylthio)ethyl] isocyanurates, respectively.
Earlier [1] we reported the synthesis of a series of
1-alkyl 3,5-bis( -haloalkyl)-1,3,5-triazine-2,4,6-
O
(1H,3H,5H)-triones whose reaction with thiourea
followed by hydrolysis of the resulting isothiuronium
salts gave rise to 1-alkyl 3,5-bis( -mercaptoalkyl)
isocyanurates [2]. Proceeding with these studies, we
developed in the present work methods for synthesis
of a series of -functionally substituted isocyanurates
with heteroatoms (O, S) in the N-alkyl chain, which
are of interest as starting materials for subsequent
syntheses and as building blocks for constructing
macrorings with isocyanurate fragments [3].
RN
N(CH2)2X(CH2)2Y
O
O
N
(CH2)2X(CH2)2Y
I X
R = C6H5CH2, CH3; X = O, S; Y = Cl, Br, OH, SH (for R,
X, Y, see Table 1).
bis(2-chloroethyl) sulfide (yperite) [4], but we con-
sidered this approach hardly practicable because of
the high toxicity of yperite. Therefore, 1-alkyl 3,5-bis-
[2-(2-chloethylthio)ethyl] isocyanurates V and VI
were obtained by reaction of 1-alkyl 3,5-bis(2-chloro-
ethyl) isocyanurates XI and XII with NaSCH2CH2OH
with subsequent treatment of the resulting 1-alkyl
1-Benzyl and 1-methyl 3,5-bis[2-(2-haloethoxy)-
ethyl] isocyanurates I IV in yields of 46 71% were
prepared similarly to bis( -haloalkyl) isocyanurates
[1] by alkylation of anhydrous disodium alkyl iso-
cyanurates with excess , -dichlorodiethyl or , -di-
bromodiethyl ethers (Chlorex and Bromex) (Table 1).
3,5-bis[2-(2-hydroxyethylthio)ethyl]
isocyanurates
The disodium salts could also be alkylated with
VII and VIII with thionyl chloride.
O
O
+ 2NaSCH2CH2OH
RN
N(CH2)2S(CH2)2OH
O
RN
N(CH2)2Cl
O
O
O
N
N
(CH2)2S(CH2)2OH
(CH2)2Cl
XI, XII
O
N
VII, VIII
SOCl2
RN
N(CH2)2S(CH2)2Cl
O
O
(CH2)2S(CH2)2Cl
V, VI
1070-3632/01/7108-1261$25.00 2001 MAIK Nauka/Interperiodica

1262
FATTAKHOV et al.
Table 1. Yields, Rf values, and elemental analyses of compounds I X
Found, %
Hlg
Comp.
no.
Yield,
%
Rf (solvent
for crystallization)
R
X
Y
C
H
N
S
I
II
C6H5CH2
CH3
C6H5CH2
CH3
C6H5CH2
CH3
C6H5CH2
O
O
O
O
S
Cl
Cl
Br
Br
Cl
70
49
71
46
61
65
60
0.33 (benzene ethyl acetate, 10: 1)
0.20 (benzene ethyl acetate, 10: 1)
0.33 (benzene ethyl acetate, 10: 1)
0.39 (benzene ethyl acetate, 5: 1)
0.50 ( benzene ethyl acetate, 1: 1)
0.35 (diethyl ether hexane, 1: 1)
0.38 (benzene methanol, 5: 1)
0.29 (ethyl acetate)
49.84
40.29
41.47
32.86
46.29
37.45
49.79
5.24
5.04
4.47
4.43
5.01
5.00
6.33
15.91
11.47 19.68
30.63
35.64
14.85
9.66
III
IV
V
VI
VII
8.03
9.24
9.37 14.02
S
S
Cl
OH
18.18 10.85 16.77
10.16 15.25
VIII
IX
X
CH3
C6H5CH2
CH3
S
O
O
OH
SH
SH
85
50
57
0.39 (benzene methanol, 5: 1)
0.31 (benzene ethyl acetate , 5: 1)
0.31 (diethyl ether hexane, 2: 1)
0.71 (diethyl ether)
40.79
50.00
40.36
6.03
6.32
6.10
12.23 18.46
9.37 14.98
11.26 18.58
Calculated, %
Hlg
Compound no.
Formula
C
H
N
S
I
II
C18H23Cl2N3O5
C12H19Cl2N3O5
C18H23Br2N3O5
C12H19Br2N3O5
C18H23Cl2N3O5S2
C12H19Cl2N3O5S2
C18H25N3O5S2
C12H21N3O5S2
C18H25N3O5S2
C12H21N3O5S2
50.01
40.46
41.48
32.38
46.55
37.12
50.57
41.01
50.57
41.01
5.36
5.38
4.45
4.30
4.99
4.93
5.89
6.02
5.89
6.02
16.40
11.18
30.66
35.90
15.28
18.26
9.66
19.91
8.06
9.44
9.05
10.82
9.83
11.96
9.83
III
IV
V
VI
VII
VIII
IX
X
13.81
16.51
15.00
18.25
15.00
18.25
11.96
O
C6H5CH2N
O
VII +
N(CH2)2Cl
MeOH, 6 h
O
XI + 2NaSCH2CH2OH
N
(CH2)2S(CH2)2OH
XIII
R = C6H5CH2 (XI), CH3 (XII).
The reaction of 1-benzyl 3,5-bis(2-chloroethyl)
isocyanurate (XI) with NaSCH2CH2OH in methanol
(boiling, 6 h) gave, along with compound VII, a
monosubstitution product, 1-benzyl 3-(2-chloroethyl)
5-[2-(2-hydroxyethylthio)ethyl] isocyanurate (XIII) in
19% yield. The same reaction in DMF resulted in
exclusive formation of a disubstitution product
(Table 1, compound VIII). Treatment of compound
XIII with thionyl chloride provided 1-benzyl 3-(2-
O
C6H5CH2N
O
N(CH2)2Cl
SOCl2
XIII
O
N
(CH2)2S(CH2)2Cl
XIV
chloroethyl) 5-[2-(2-chloroethylthio)ethyl] isocyanu-
rate (XIV).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 8 2001

FUNCTIONALLY SUBSTITUTED ISOCYANURATES WITH HETEROATOMS (O, S)
1263
Table 2. IR and 1H NMR spectra of compounds I X
1
IR spectruma (thin layer), , cm
Compound no.
triazine ring [5]
C=O
CO
OH
SH
I
II
753 s
755 s
750 s
750 s
750 s
745 s
745 s
750 s
750 s
745 s
1740 m, 1675 s
1740 s, 1675 s
1740 m, 1675 s
1750 m, 1686 s
1690 s
1740 m, 1675 s
1664 s
1740 m, 1673 s
1675 s
1115 s
1110 s
1114 s
1114 s
III
IV
V
VI
VII
VIII
IX
X
1033 s
1040 s
1100 s
1100 s
3340 s
3350 s
2557 m
2557 m
1748 m, 1686 s
1H NMR spectrum (CCl4), , ppmb
Comp.
no.
CH3
C6H5 C6H5CH2
NCH2
OCH2
CH2Hlg
SCH2
SH
(3JHH 6 Hz)
(3JHH 8 Hz)
I
II
7.16 m 4.92 s
7.21 m 4.95 s
7.21 m 4.95 s
7.28 m 5.03 s
4.00 t
4.02 t
4.03 t
4.04 t
4.00 t
4.00 t
4.08 t
3.30 3.72 m
3.26 3.75 m
3.30 s
3.27 s
3.30 s
III
IV
V
VI
VII
3.58 3.80 m
3.53 3.83 m
3.26 t (3JHH 6 Hz)
3.26 t (3JHH 6 Hz)
3.74 t (3JHH 8 Hz)
3.60 t (3JHH 8 Hz)
2.95 m
3.00 m
2.65 2.95 m
3.73 t
(3JHH 5.5 Hz)
3.81 t
VIII 3.37 s
4.14 t
4.00 t
4.00 t
2.68 2.95 m
(3JHH 5.5 Hz)
3.37 3.83 m
IX
7.27 m 4.95 s
2.50 q
1.38 t
1.40 t
(4JHH 7 Hz)
2.40 2.83 m
X
3.28 s
3.43 3.68 m
a
1
Along with the listed bands, the spectra of compounds I X contain strong bands at, cm , 2960 2860 [ (CH)] and 1450
[ (CH )], as well as 3030 m, 1600 w, 1570 w, 694 s (benzene ring) or 1370 1360 s [ (CH )].
2
3
b
1
The H NMR spectra of compounds VII and VIII were obtained in CDCl .
3
Compounds III and IV were reacted with thiourea,
1-Benzyl and 1-methyl 3,5-bis[2-(2-chloro-
ethoxy)ethyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-
triones (I, II). Benzyl isocyanurate VII or methyl
isocyanurate VIII, 0.05 mol, was added with stirring
to sodium butylate obtained from 0.1 mol of sodium
in 300 ml of absolute butanol, and the mixture was
boiled for 8 h. The butanol was distilled off in a
vacuum, the residual solvent was removed by azeo-
tropic distillation with toluene, and the residual
toluene was distilled off in a vacuum. The dry di-
sodium salt that remained was treated with 300 ml of
absolute DMF and 0.5 mol (5-fold excess) of
Cl(CH2)2O(CH2)2Cl, the mixture was stirred at 85
90 C for 4 5 h (to pH 7), and the precipitate was
filtered off. The DMF and Chlorex were removed in a
and the resulting isothiuronium salts were hydrolyzed
to obtain thiols IX and X in 50 60% yields (Table 1).
The reactions of chloro derivatives I and II with thio-
rea (boiling in isopropanol, 16 18 h) gave no iso-
thiuronium salts.
EXPERIMENTAL
The IR spectra were recorded on a Specord IR-75
instrument in thin film or in suspensions in mineral
1
oil. The H NMR spectra were measured on a Varian
T-60 at 60 MHz, internal reference tetramethylsilane.
1
The H NMR and IR spectra of compounds I X
are given in Table 2.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 8 2001

1264
FATTAKHOV et al.
vacuum, and the residue was subjected to column
chromatography on silica gel, eluent benzene ethyl
acetate, 10:1. Compounds I and II are transparent
yellowish thick oils.
694 s, 670 s (benzene ring), 2906 s, 2940 s (CH),
1740 m, 1680 s (C=O), 1440 s [ (CH2)], 1040 m
(CO), 750 m (triazine ring). 1H NMR spectrum
(CDCl3), , ppm: 2.53 2.83 m (4H, SCH2), 3.53
3.73 m (4H, CH2Cl and CH2O), 4.00 t (4H, NCH2,
3JHH 6 Hz), 4.93 s (2H, C6H5CH2), 7.18 m (5H,
C6H5). Found, %: C 50.01; H 5.13; Cl 8.95; N 10.45;
S 8.41. C16H20ClN3O4S. Calculated, %: C 49.80; H
5.22; Cl 9.19; N 10.89; S 8.31.
1-Benzyl and 1-methyl 3,5-bis[2-(2-bromoeth-
oxy)ethyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-triones
(III, IV) were obtained in a similar way. The reac-
tions were performed at 45 50 C. Compounds III and
IV are transparent yellowish thick oils.
From the benzene methanol fraction we isolated
3.15 g (60%) of compound VII as an oil that crystal-
lized on standing.
1-Benzyl and 1-methyl 3,5-bis[2-(2-chloroethyl-
thio)ethyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-triones
(V, VI). Thionyl chloride, a 5-fold molar excess, was
slowly added at 10 15 C to a solution of compound
VII or VIII in absolute 1,2-dichloroethane, and the
mixture was boiled for 3 h. After cooling, it was
treated with water, the organic layer was dried with
MgSO4, the solvent was removed, and the residue was
subjected to column chromatography on silica gel,
1-Methyl-3,5-bis[2-(2-hydroxyethylthio)ethyl]-
1,3,5-triazine-2,4,6(1H,3H,5H)-trione (VIII).
2-Mercaptoethanol, 1.1 g, was added to sodium me-
thylate obtained from 0.31 g of sodium in 40 ml of
absolute methanol, and the mixture was stirred for
15 min. The methanol was removed in a vacuum, and
eluent benzene ethyl acetate (first 10:1 and then 5:1). the residue was treated with 30 ml of absolute DMF
Compounds V and VI were isolated as transparent
oils, and compound V crystallized on standing.
and 1.8 g of 1-methyl-3,5-bis(2-chloroethyl)-1,3,5-tri-
azine-2,4,6(1H,3H,5H)-trione (XII). The mixture
was stirred for 1 h at 30 C, cooled, the precipitate was
filtered off, the DMF was removed in a vacuum, and
the residue was subjected to column chromatography
in the above-described conditions to isolate 2 g (85%)
of compound VIII as a transparent thick oil.
1-Benzyl-3-(2-chloroethyl)-5-[2-(2-chloroethyl-
thio)ethyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione
(XIV) was obtained in a similar way by treatment
with thionyl chloride of compound XIII. The eluent
for chromatography was benzene. Yield 65%, trans-
parent tar. Rf 0.33 (ether hexane, 1:1). IR spectrum
1-Benzyl and 1-methyl-3,5-bis[2-(2-mercapto-
ethoxy)ethyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-tri-
ones (IX, X). Equimolar amounts of compound III or
IV and thiourea were boiled in isopropanol for 4
12 h. The alcohol was removed in a vacuum, and the
residue was treated with aqueous K2CO3, stirred for
90 C (on a water bath) for 2 h, and extracted with
methylene chloride. The aqueous layer was acidified
with HCl, and extracted with methylene chloride. The
extract was dried with MgSO4 and purified on a
column of silica gel. Compound IX: eluent benzene
ethyl acetate, 10:1. Yield 50%, transparent yellowish
oil. Compound X: eluent benzene ethyl acetate,
7.5:1. Yield 57%, transparent yellowish oil, crystal-
lizes on standing, mp 103 105 C (from benzene).
1
(thin film), , cm : 3030 m, 1580 w, 1600 w, 700 s,
680 s (benzene ring), 2960 s, 2920 s (CH), 1690 s
1
(C=O), 1464 s [ (CH2)], 747 m (triazine ring). H
NMR spectrum (CCl4), , ppm: 2.63 2.95 m (4H,
SCH2), 3.42 3.73 m (4H, CH2Cl), 4.00 t (4H, NCH2,
3JHH 6 Hz), 4.95 s (2H, C6H5CH2), 7.22 m (5H,
C6H5). Found, %: C 47.68; H 4.81; Cl 17.36; N 10.18;
S 8.08. C16H19Cl2N3O3S. Calculated, %: C 47.53; H
4.74; Cl 17.54; N 10.39; S 7.93.
1-Benzyl-3,5-bis[2-(2-hydroxyethylthio)ethyl]-
1,3,5-triazine-2,4,6(1H,3H,5H)-trione (VII).
2-Mercaptoethanol, 2 g, and 4.3 g of 1-benzyl-3,5-bis-
(2-chloroethyl)-1,3,5-triazine-2,4,6(1H,31H,51H)-
trione (XI) were added to sodium methylate obtained
from 0.57 g of sodium in 50 ml of absolute methanol,
and the mixture was boiled for 6 h. The precipitate
1-Methyl-3,5-bis(2-chloroethyl)-1,3,5-triazine-
2,4,6(1H,3H,5H)-trione (XII) was obtained by
was filtered off, and the filtrate was evaporated in a treatment with thionyl chloride of 1-methyl 3,5-bis-
vacuum. The residue was subjected to column chro-
matography on silica gel, eluents benzene ethyl
acetate, 5:1, and benzene methanol, 5:1, in succes-
sion. From the benzene ethyl acetate fraction we ob-
tained 1 g (19%) of 1-benzyl-3-(2-chloroethyl)-5-[2-
(2-hydroxyethylthio)ethyl]-1,3,5-triazine-2,4,6(1H,
3H,5H)-trione (XIII) as a transparent oil. Rf 0.45
(benzene ethyl acetate, 1:1). IR spectrum (thin film),
(2-hydroxyethyl) isocyanurate similarly to compound
XIII [1]. Yield 56%, mp 114 115 C (from benzene).
Rf 0.25 (ether hexane, 1:1). IR spectrum (Vaseline),
1
, cm : 1750 m, 1665 v.s (C=O), 747 m (triazine
ring). 1H NMR spectrum (CDCl3), , ppm: 3.32 s (3H,
3
CH3), 3.68 t (4H, CH2Cl, JHH 7 Hz), 4.21 t (4H,
3
NCH2, JHH 6.5 Hz). Found, %: C 35.80; H 4.06; Cl
25.15; N 15.52. C8H11Cl2N3O3. Calculated, %: C
35.84; H 4.14; Cl 25.45; N 15.67.
1
, cm : 3425 m (OH), 3030 m, 1580 w, 1600 w,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 8 2001

FUNCTIONALLY SUBSTITUTED ISOCYANURATES WITH HETEROATOMS (O, S)
1265
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 8 2001