Synthesis of amino derivatives of 1,3,5-triazines containing hetero- and carbocyclic moieties

Article abstract of DOI:10.1134/S1070427212020139

Reactions of chloro-sim-triazines with secondary amines containing 1,3-dioxolane and hemdichlorocyclopropane moieties were studied. Structures of amino derivatives of 1,3,5-triazines containing cyclic acetal and cyclopropane moieties were examined. Pleiad

Full text of DOI:10.1134/S1070427212020139

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2012, Vol. 85, No. 2, pp. 239−243. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © S.A. Timofeeva, G.Z. Raskil’dina, L.V. Spirikhin, S.S. Zlotskii, 2012, published in Zhurnal Prikladnoi Khimii, 2012, Vol. 85, No. 2,
pp. 250−254.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Synthesis of Amino Derivatives of 1,3,5-Triazines Containing
Hetero- and Carbocyclic Moieties
S. A. Timofeevaa, G. Z. Raskil’dinab, L. V. Spirikhinc, and S. S. Zlotskiid
aUfa State Academy of Economics and Services, Ufa, Bashkortostan, Russia
bResearch Institute of Herbicides and Plant Growth Regulators, with a Pilot Plant,
Academy of Sciences of the Republic of Bashkortostan, Ufa, Bashkortostan, Russia
cInstitute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, Bashkortostan, Russia
dUfa State Technical University of Oil, Ufa, Bashkortostan, Russia
e-mail: Timofeeva_s_a@mail.ru
Received July 11, 2011
Abstract—Reactions of chloro-sim-triazines with secondary amines containing 1,3-dioxolane and hem-
dichlorocyclopropane moieties were studied. Structures of amino derivatives of 1,3,5-triazines containing cyclic
acetal and cyclopropane moieties were examined.
DOI: 10.1134/S1070427212020139
Cyanuric chloride (I) and other chloro-sim-triazines
are widely used to manufacture biologically active sub-
stances, additives, and various small-tonnage products
with wide spectrum of useful action [1, 2]. It is known
that substitution of a chlorine atom in a trichloride with
amino groups occurs in steps [3], with mono- and disub-
stituted derivatives formed.
To obtain hetero- and carbocyclic amino derivatives
of triazines, we studied the reaction of cyanuric chloride
(I) with secondary amines containing 1,3-dioxolane
Scheme.
Cl
N
Cl
R
N
N
N
N
N
R
+
H
Cl
N
Cl
N
Cl
I
IIa, IIb
IIIa, IIIb
Cl
N
N
N
R
R
R
N
N
N
+
H
IVa, IVb
Cl
Cl
O
IIa, IIIa, IVa;
O
R =
IIb, IIIb, IVb;
239

240
TIMOFEEVA et al.
(IIa) and hem-dichlorocyclopropane (IIb) moieties.
As a result, the corresponding mono- and disubstituted
derivatives IIIa, IIIb and IVa, IVb were obtained
according to the scheme.
from protons of the aromatic ring.
A characteristic feature of 13C NMR spectra of the
synthesized compounds IIIa, IIIb and IVa, IVb is
the presence of signals in the weak-field part of the
spectrum, which correspond to carbon atoms of the
triazine ring. The chemical shifts of 165.49 (IIIa),
165.42 (IIIb), 165.09 (IVb), 165.39 and 165.61 ppm
(IVa) correspond to carbons C–N bonded to the amine,
and those of 170.59 (IIIb), 167.7 (IVa), 170.16 (IVb),
170.32 and 170.49 ppm (IIIa), to carbon atoms of the
triazine ring with a C–Cl bond.
Atanequimolarratiobetweenthereagents(secondary
amine : triazine = 1 : 1), the corresponding mono amino
derivatives are formed in anhydrous 1,4-dioxane. As
the molar ratio between a secondary amine and triazine
increases from 1 : 1 to 2 : 1, disubstituted triazines IVa,
IVb become the main reaction products (see the table).
It is noteworthy that, judging from the yields of the
triazines formed, secondary amines IIa and IIb are
close in activity.
In the mass spectra of the synthesized compounds
IIIa, IIIb and IVa, IVb , molecular ions are
characterized by low-intensity peaks (<<1%). In all
The structure of the synthesized and isolated amino
substituted triazines was confirmed by 1H and 13C NMR
spectroscopic and chromato-mass-spectrometric data.
the spectra, the maximum intensity is observed for the
+
[ArCH
2] . ion with m/z = 91 (100%). Under the electron
1
impact, molecular ions of amino derivatives of triazine
form high-intensity ions of N-benzyl-N-(1,3-dioxolan-
4-yl)methylamine or N-benzyl-4,6-dichloro-N-[(2,2-
dichlorocyclopropyl)methylamine substituents, which
further decompose.
An analysis of the H NMR spectrum of compound
IIIa demonstrated that Hb1’ and Hb protons in the trans
5
position with respect to the proton of the C4H group of
the dioxolane ring have a chemical shift (CS) at 3.50
and 3.56 ppm in the form of doublet-doublets with spin-
spin coupling constants (SSCCs) (Hz): 2J1' = 14.4, 2J5 =
The content of ions corresponding to the presence
of a triazine ring in the spectrum does not exceed
10% for IIIa, IIIb and 5% for IVa, IVb. Destruction
of the triazine ring in the molecular ion M+. of the
compounds occurs with loss of HNCCl and formation
of [C4H7O2NHCNCH2Cl]+ moiety (m/z = 176/178) for
IIIa and IVa and [ArCH2C4H7O2NCNCCl]+. (m/z =
266/268) for (IVa).
3
3
5
8.4, J1'b-4 = 8.1, and J5b-4 = 5.7. The protons Ha and
Ha in the cis-position to the C4H proton are observed
1'
2
with CS 3.80 and 3.88 ppm (SSCC, Hz: J1' = 14.4,
2J4 = 8.4, J1'a-4 = 3.1, J5a-4 = 6.2). The proton of the
CH group of the cyclic acetal appears as four doublets at
4.36 ppm, with SSCCs (Hz): 3J1'b-4 = 8.1, 3J1'a-4, 3J5a-4
6.2, 3J5b-4 = 5.7. Atoms of the CH2 group of the second
atom have CS = 4.85 and 5.06 ppm in the form of two
high-intensity singlets. Signals of methylene protons of
the benzyl group form two doublets with CS = 4.7 and
5.53 ppm (SSCC 2J = 15.4 Hz) and a multiplet in the
range 7.2–7.4 ppm from protons of the aromatic ring.
The structure of compound IVa was determined in
a similar way.
3
3
=
EXPERIMENTAL
1H and 13C NMR spectra were recorded with
a Bruker AM-300 spectrometer (300.13 and 75.43MHz,
respectively) in CDCl3 with Me4Si as internal standard;
and chromato-mass spectra, with a Shimadzu GCMS-
QP2010 Plus (electron impact, 70 eV, ion source tem-
perature 200°C, direct input temperature 40–290°C,
heating rate 12 deg min–1). A GLC analysis was made
on an LKhM-8MD chromatograph with a heat-conduc-
tivity detector, helium as carrier-gas with a flow rate of
1.5 l h–1, and 2-m-long column packed with 5% SE-30
on Chromaton N-AW. A TLC analysis was made on
alufol Merck chromatographic plates (20 : 1 benzene–
methanol mixture as eluent). A preparative separation
was performed by column chromatography on alumi-
num oxide, with the role of eluent played by benzene
with a methanol content increasing from 5 to 100%.
1
The H NMR spectrum of compound IIIb demon-
strated that the proton of the CH group of the cyclo-
propane ring appears at CS = 1.9 ppm as four doublets
with SSCCs (Hz): 3J2a-3 = 10.7, 3J2b-3 = 7.6, 3J1'a-3 = 7.7,
3J1'b-1 = 5.8. Protons of the CH2 groups bonded to the ni-
trogen atom are characterized by the presence of a dou-
blet-doublet signal with CS = 3.5 ppm (SSCC, Hz: 2J =
14.6, 3J1'a-1 = 7.7) for C1'Ha and 4.00 ppm (2J = 14.7 Hz,
3J1'b-1 = 5.8 Hz) for C1'Hb. As also in compound IIIa, to
the benzyl group belong two doublets with CS = 4.8 and
5.3 ppm (SSCC 2J = 15.4 Hz), which correspond to sig-
nals from the CH2 group, and a multiplet at 7.2–7.4 ppm
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SYNTHESIS OF AMINO DERIVATIVES OF 1,3,5-TRIAZINES
241
Interaction of secondary amines containing 1,3-dioxolane and hem-dichlorocyclopropane moieties with chloro-sim-triazines.
A : B molar ratio 0.007 : 0.007, 20 ml of 1,4-dioxane. T = 80–90°C, 2 h
Yield,
%
(C:D)
Reac-
Starting compound
Product
tants
ratio
A
B
C
D
Cl
N
N
N
N
1 : 1
73
Cl
O
O
Ph
O
IIIa
H
O
N
Ph
Cl
N
Cl
N
IIa
N
N
N
N
86
1 : 2
N'
Ph
N
Cl
N
(1 : 8)
O
O
O
O
O
O
Ph
Cl
N
Ph
IIIa
IVa
N
N
Cl
Cl
Cl
N
N
I
1 : 1
80
Cl
N
N
Ph
Cl Cl
IIIb
H
N
Cl
Cl
Ph
Cl
Cl
N
IIb
N
N
N
N
85
(1 :
16)
1 : 2
Cl
N
N
N'
N
Ph
Ph
Ph
Cl Cl
Cl Cl
Cl Cl
IIIb
IVb
N-Benzyl-(1,3-dioxolan-4-yl)methylamine (IIa).
microwave irradiation zone).After the reaction was
complete, the mixture was cooled to 20–25°C, washed
with a twofold amount of water, and twice extracted
with diethyl ether. The ether extract was shaken with
a 10% solution of NaOH, washed with water to neutral
reaction, dried with K2CO3, and ether was evaporated in
a rotor evaporator. The residue was subjected to vacuum
distillation in the atmosphere of nitrogen.
A 50-ml reactor equipped with a mechanical stirrer,
reflux condenser, and thermometer was charged with
0.08 mol (8.56 g) of benzylamine, 0.12 mol (6.72 g) of
solid KOH, 0.05 mol (6.15 g) of 4-chloromethyl-1,3-
dioxolane, 0.24 g of TEBAC, and 20 ml of DMSO. The
reaction mixture was agitated and irradiated in a Sanyo
EM-S1073W microwave oven (power 250 W) for 0.5 h.
The temperature was 20–25°C at the beginning of a run
and increased in the process to 35–40°C (outside the
Mass spectrum (electron impact, 70 eV), m/z (Jrel,
%): 193 [M+] (0), 192 (0.5), 162 (2), 148 (7), 120 (100),
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 85 No. 2 2012

242
TIMOFEEVA et al.
91 (100), 77 (3), 65 (10). 1H NMR spectrum (CDCl3, δ,
ppm, J, Hz): 2.75 s (2N, C1’N2), 3.63 t (1N, C5Nb, 2J 9.0,
(3/1), 211 (5), 207 (4), 182 (7), 183 (3) , 176/178/180
(6/3/0.5), 157 (11), 150 (11), 148 (7), 132 (4), 131 (42),
125 (13), 116 (8), 104 (57), 91 (100) , 79 (35), 65 (50),
62/64 (42/20.5). 1H NMR spectrum (CDCl3, δ, ppm, J,
Hz): 3.50 d.d (1H, C1'Hb, 2J 14.4, 3J 8.1), 3.56 d.d (1H,
C5Hb, 2J 8.4, 3J 5.7), 3.80 d.d (1H, C1'Ha, 2J 14.4, 3J 3.1),
2
3J 9.0), 3.84 s (1N, C1’’Na), 3.95 t (1N, C5Nb, J 9.0,
3
3J 9.0), 4.20 kV (1H, C5H, J 9.0), 4.86 s (1H, C2Ha),
5.01 s (1H, C2Hb), 7.20–7.40 m (5H, Ph–).
N-Benzyl-1,1-(2,2-dichlorocyclopropyl)methyl-
amine (IIb). To a mixture of 0.1 mol (10.7 g) of
benzylamine, 0.025 mol of 2-chloromethyl-1,1-
dichlorocyclopropane was poured 30 ml of DMSO. The
reaction mixture was agitated for 4 h at 70–75°C. On
being cooled, it was washed with a 20% NaOH solution
and extracted with ether; the extract was washed with
water to neutral reaction and dried with K2CO3. After
the solvent, ether, was evaporated, the residue was
distilled in a vacuum in the atmosphere of nitrogen.
Mass spectrum (electron impact, 70 eV), m/z (Jrel, %):
228/230/232 [M+] (12/8/3), 194/196 (5/1), 165 (2), 151
(6), 147 (8), 146 (68), 133 (14), 132 (37), 120 (42), 118
(7), 104/106/108 (18/14/3), 91 (43), 90/92 (100/25), 89
(11), 77 (6), 65 (30). 1H NMR spectrum (CDCl3, δ, ppm,
2
3
3.98 d.d (1H, C5Hb, J 8.4, J 6.2), 4.36 d.d.d.d (1H,
C4H, 3J 8.1, 3.1, 5.7, 6.2), 4.85 s (1H, C2Ha), 5.06 s (1H,
2
C2Hb), 4.79 d (1H, C1''Ha, J 15.1), 5.3 d (1H, C1''Hb,
2J 15.1), 7.20–7.40 m (5H, Ph–). 13C NMR spectrum
(CDCl3, δ, ppm): 48.39 (1'C); 51.54 (1''C); 67.54 (5C);
73.92 (4C); 95.15 (2C); 128.07 (6'''C); 128.02 (3'''C, 5'''C);
128.89 (2'''C, 4'''C); 135.63(1'''C); 165.49 (2''''C); 170.32,
170.49 (5''''C, 4''''C).
N-Benzyl-4,6-dichloro-N-[(2,2-dichlorocyclo-
propyl)methyl]-1,3,5-triazine-2-amine (IIIb). Yield
80%, isolated by column chromatography (Rf = 0.78,
20 : 1 benzene–methanol as eluent). Mass spectrum, m/z
(Jrel, %): 376/378/380/382 [M+] (0), 268/270 (0.3/0.2),
242/244/246 (3.5/1.8/0.3), 207 (1), 192/194 (0.8/0.4),
132 (2), 104 (5), 92 (3), 91 (100) , 87 (8.5), 65 (11).
1H NMR spectrum (CDCl3, δ, ppm, J, Hz): 1.2 t (1H,
C2Hb, 2J 7.6, 3J 7.6), 1.7 d.d (1H, C2Ha, 2J 7.6, 3J 10.7),
2
3
J, Hz): 1.17 t (1H, C2Hb , J 7.4, J 7.4), 1.65 d.d (1H,
C2Ha, J 7.4, J 10.4), 1.85 d.d.d.d (1H, C3H, J 7.4,
10.4, 8.3, 5.6), 2.75 d.d (1H, C1'Ha, 2J 12.8, 3J 8.3), 2.9
d.d (1H, C1'Hb, 2J 12.8, 3J 5.6), 3.85 s (2H, C1''H2), 7.20–
7.40 m (5H, Ph–).
3
2
3
3
1.9 d.d.d.d (1H, C3H, J 7.6, 10.7, 7.7, 5.8), 3.50 d.d
(1H, C1’Ha, 2J 14.6, 3J 7.7), 4.00 d.d (1H, C1’Hb, 2J 14.6,
3J 5.8), 4.80 d (1H, C1’’Ha, 2J 15.3), 5.30 d (1H, C1’’Hb,
2J 15.3), 7.20–7.40 m (5H, Ph–). 13C NMR spectrum
(CDCl3, δ, ppm, J, Hz): 25.71 (2C), 28.52 (3C), 47.10
(1'C), 50.55 (1''C), 59.80 (1C), 128.31 (4'''C), 127.76 (3'''C,
5'''C), 128.97 (2'''C, 4'''C), 135.52 (1'''C), 165.42 (2''''C),
170.59 (4''''C, 6''''C).
Interaction of secondary amines with chloro-
sim-triazine (1 : 1). A mixture of 0.007 mol (1.29 g) of
cyanuric chloride (Ia) and 0.007 mol of amine IIa, IIb
[1.35 g of N-benzyl-(1,3-dioxolan-4-yl)methylamine
or 1.61 g of N-benzyl-1-1-(2,2-dichlorocyclopropyl)
methylamine] in 20 ml of dioxane was boiled under
agitation for 3 h, then cooled to 20°C, a solution of
0.39 g (0.007 g-mol) of KOH in 5 ml of water was added,
and the mixture was boiled under agitation for 1 h. The
mixture was cooled to 10–15°C, 100 ml of icy water
was added, and the resulting mixture was washed with
benzene (3 Ч 30 ml). The extract was dried over Na2SO4,
concentrated to a volume of 5 ml, and chromatographed
on a column with Al2O3 (H = 20 cm, d = 4.5 cm), with
elution by a 20 : 1 mixture of benzene and methanol.
This procedure was used to obtain compounds IIIa and
IIIb.
Interaction of secondary amines with chloro-
sim-triazines (2 : 1). A mixture of 0.007 mol (1.29 g)
of cyanuric chloride Ia and 0.014 g-mol of amine IIa,
IIb [3.1 g of N-benzyl-(1,3-dioxolan-4-yl)methylamine
or 3.22 g of N-benzyl-1-1-(2,2-dichlorocyclopropyl)
methylamine] in 20 mL of 1,4-dioxane was boiled under
agitation for 3 h, then it was cooled to 20°C, a solution
of 0.78 g (0.014 g-mol) of KOH in 5 mL of water was
added, and the mixture was boiled under agitation for
1 h. Then the mixture was cooled to 10–15°C, 100 ml
of icy water was added, and washed the resulting
mixture with benzene (3 Ч 30 ml). The extract was dried
over Na2SO4, concentrated to a volume of 5 ml, and
chromatographed on a column with Al2O3 (H = 20 cm,
d = 4.5 cm), with elution by a 40 : 1 benzene–ethanol
mixture. This procedure was used to obtain compounds
IVa and IVb.
N-Benzyl-4,6-dichloro-N-(1,3-dioxolan-4-
ylmethyl)-1,3,5-triazine-2-amine (IIIa). Yield 73%,
isolated by column chromatography (Rf = 0.65) (20 : 1
benzene–methanol as eluent). Mass spectrum (electron
impact, 70 eV), m/z (Jrel, %): 340/342/343 [M+] (0),
254/256/258 (24/14/3), 252/254/256 (10/7/4), 219/221
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 85 No. 2 2012

SYNTHESIS OF AMINO DERIVATIVES OF 1,3,5-TRIAZINES
243
1H, C1'''''Ha, 2J 15.4), 5.30 d (1H, C1''''Hb, 2J 15.4, d, 1H,
C1'''''Hb, 2J 15.4), 7.20–7.40 m (5H, Ph''''''–, 5H, Ph''''''–).
13C NMR spectrum (CDCl3, δ, ppm, J, Hz): 25.31, 25.03
(2C, 2'C); 29.07, 28.61 (3C, 2'C); 46.20, 47.14 (1'C, 1'''C);
49.72, 50.49 (1'''C, 1''''C); 60.05, 60.13 (1C, 1'C); 127.01,
127.42 (4'''''C, 4''''''C); 127.49, 127.58 (3'''''C, 3''''''C, 5'''''C,
5''''''C); 127.96, 128.33 (2'''''C, 2''''''C, 6'''''C, 6''''''C), 136.97
N,N'-Dibenzyl-6-chloro-N,N'-bis(1,3-dioxolan-
4-ylmethyl)-1,3,5-triazine-2,4-diamine (IVa). Yield
76%, isolated by column chromatography (Rf = 0.55, 40 :
1 benzene–methanol mixture as eluent. Mass spectrum
(electron impact, 70 eV), m/z (Jrel, %): 496/498 [M+]
(0), 266/268 (1.4/0.9), 218/220 (0.4/9.2), 207 (4), 190
(0.3), 176/178 (0,5/0.3), 131 (0.9), 104/106 (1.9/1), 91
(100), 92 (7), 87 (1.7), 65 (11), 62/64 (2/1.1). 1H NMR
spectrum (CDCl3, δ, ppm, J, Hz): 3.20–4.10 m (8H,
C1''H2, C1'''H2, C5H2, C5'H2); 4.35 m (2H, C4H, C4'H),
4.85 s (1H, C2Ha, s, 1H, C2'Ha); 5.02 s (1H, C2Hb, s,
(
1'''''C, 1''''''C); 165.09 (2'''''''C, 4'''''''C); 170.16 (6'''''''C).
CONCLUSIONS
2
1H, C2'Hb); 4.79 d (2H, C1'''Ha, C1''''Ha, J 15.6); 5.15,
(1) The reaction of chloro-sim-triazines with
2
2
5.20 d (1H, C1''''Hb, d, 1H, C1'''Hb, J 13.5, J 15.1);
7.20–7.40 m (10H, Ph–). 13C NMR spectrum (CDCl3,
δ, ppm, J, Hz): 48.21, 48.79 (1'C, 1'''C); 50.86, 51.32
secondary amines containing 1,3-dioxolane and hem-
dichlorocyclopropane moieties was used to obtain the
corresponding mono- and disubstituted derivatives.
5'
(1'''C, 1''''C); 67.32, 67.63 (5C, C); 74.91, 75.03 (4C,
(2) The structure of the synthesized amino derivatives
4'C); 94.85, 95.00 (2C, 2'C); 128.09 (4'''''C, 4''''''C); 127.59,
127.48 (3'''''C, 3''''''C, 5'''''C, 5''''''C); 127.70, 128.61 (2'''''C,
2''''''C, 6'''''C, 6''''''C), 137.44, 137.59 (1'''''C, 1''''''C); 165.39,
165.61 (2'''''''C, 4'''''''C); 167.71 (6'''''''C).
1
of 1,3,5-triazines was confirmed by H and 13C NMR
spectroscopy, and the disubstituted structure of the
compounds, by chromato-mass spectrometry.
(3) It was demonstrated that reactions of amines
with chloro-sim-triazines in anhydrous 1,4-dioxane are
a convenient way to synthesize the corresponding amino
derivatives of triazines.
N,N'-Dibenzyl-6-chloro-N.N'-bis[(2,2-dichloro-
cyclopropyl)methyl]-1,3,5-triazine-2,4-diamine
(IVb). Yield 80%, isolated by column chromatography
(Rf = 0.62, benzene as eluent. Mass spectrum, m/z (Jrel,
%): 569/571/573/575/577/579 [M+] (0), 280/282/284
(2.6/1.7/0.3), 278/280/282 (3.7/2.7/1.7), 252/254/256
(2.2/1.6/0.3), 207 (0.5), 188/190/192 (3.7/2.8/0.7), 131
(3.7), 128/130 (4/2.1), 125/127 (2.5/1.7), 104 (6), 92
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RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 85 No. 2 2012