Derivatives of imidazo-sym-triazine

Article abstract of DOI:10.1007/s10593-008-0143-0

2-Dimethylamino-4,6,7,8-tetrahydroimidazo[1,2-a]-sym-triazin-4-one synthesized by us previously is converted by the action of aryl isocyanates and arenesulfonyl chlorides into the corresponding derivatives of urea and N-arenesulfonyl-substituted imidazo-sym-triazinones. It was shown that 6-(2-chloroethoxy)-2-dimethylamino-4-(methoxycarbonylmethylamino)-sym-triazine is converted by thermolysis into 2-dimethylamino-8-methoxycarbonylmethyl-4,6,7, 8-tetrahydroimidazo[1,2-a]-1,3,5-triazin-4-one, which is also obtained by the action of methyl bromoacetate on the imidazo-sym-triazinone.

Full text of DOI:10.1007/s10593-008-0143-0

Chemistry of Heterocyclic Compounds, Vol. 44, No. 8, 2008
DERIVATIVES OF IMIDAZO-sym-TRIAZINE
V. V. Dovlatyan*, K. A. Eliazyan, V. A. Pivazyan, and A. P. Yengoyan
2-Dimethylamino-4,6,7,8-tetrahydroimidazo[1,2-a]-sym-triazin-4-one synthesized by us previously is
converted by the action of aryl isocyanates and arenesulfonyl chlorides into the corresponding
derivatives of urea and N-arenesulfonyl-substituted imidazo-sym-triazinones. It was shown that 6-(2-
chloroethoxy)-2-dimethylamino-4-(methoxycarbonylmethylamino)-sym-triazine
is
converted
by
thermolysis into 2-dimethylamino-8-methoxycarbonylmethyl-4,6,7,8-tetrahydroimidazo[1,2-a]-1,3,5-
triazin-4-one, which is also obtained by the action of methyl bromoacetate on the imidazo-sym-
triazinone.
Keywords: imidazo-sym-triazines, rearrangement-cyclization.
Within the framework of investigations of the rearrangement-cyclization reaction, discovered recently
by us, of chloroethoxy-sym-triazines into annelated sym-triazinones [1] it was found that on thermolysis 4-alkyl-
2-(2-chloroethoxy)-6-dialkylamino-sym-triazines split off hydrogen chloride or are subject to dechloro-
alkylation with the formation of 8-alkyl-4,6,7,8-tetrahydroimidazo[1,2-a]-1,3,5-triazin-4-ones [2]. The high
phyto and fungal activity of oxazole derivatives [3-5] directed the search for new pesticides towards the series of
8-substituted derivatives of imidazo-sym-triazinones. Using the basic approaches of the indicated procedure the
corresponding chloroethoxy derivative 2 was obtained from the quaternary ammonium salt 1. On thermolysis and
subsequent alkaline treatment compound 2 is converted into the methyl ester of (2-dimethylamino-4-oxo-
6,7-dihydro-4H-imidazo[1,2-a]-1,3,5-triazin-8-yl)acetic acid (3) and then into the corresponding hydrazide 4 (Table
1). In place of the triplet signals of the chloroethoxy group of compound 2 a multiplet is observed characteristic of
the methylene groups of the imidazole ring of compounds 3 and 4 (Table 2).
In addition, a simpler and more effective procedure for the synthesis of a series of 8-alkyl-substituted
imidazo-sym-triazinones was, in our opinion, the use of 2-substituted 7,8-dihydro-6H-imidazo[1,2-a]-1,3,5-
triazin-4-one as starting material. As an example, 2-dimethylamino-7,8-dihydro-6H-imidazo[1,2-a]-sym-triazin-
4-one 5 was synthesized by a similar cyclization procedure from 6-chloroethylamino-4-dimethylamino-
2-methoxy-sym-triazine [6]. It was shown that compound 3 is also formed on alkylation of compound 5 with
methyl bromoacetate in DMF and in the presence of potassium hydroxide (Tables 1, 2).
Urea derivatives 6a-d were formed on boiling a toluene solution of compound 5 with aryl isocyanates.
N-Acetyl (7) and N-arenesulfonyl (8a-c) derivatives were obtained by acetylation and arenesulfonylation of
compound 5.
_______
* Deceased.
__________________________________________________________________________________________
Armenian State Agrarian University, Erevan 375009; e-mail: ayengoyan@mail.ru. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1230-1235, August, 2008. Original article submitted April
6, 2006; revision submitted July 4, 2008.
0009-3122/08/4408-0991©2008 Springer Science+Business Media, Inc.
991

992

TABLE 1. Physicochemical Characteristics of Compounds 1-9
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °C
Yield, %
Cl
N
S
1
2
3
C11H21ClN6O2
12.03
11.66
12.41
12.26
27.83
27.58
24.49
24.18
27.36
27.67
—
—
—
155-156
118-119
92
89
90
C10H16ClN5O3
C10H15N5O3
—
Viscous
liquid
4
C9H15N7O2
C14H16N6O2
—
—
35.00
38.74
27.53
28.00
—
—
239–241
79
89
6a
220-222
6b
6c
C14H15ClN6O2
C14H15ClN6O2
11.00
10.61
10.22
10.61
25.53
25.11
24.79
25.11
—
—
205-207
240-242
83
90
6d
7
C14H14Cl2N6O2
C9H13N5O2
19.58
19.24
23.11
22.76
31.65
31.39
21.27
20.90
10.32
9.99
21.95
22.22
23.30
23.73
—
—
236-238
210-212
226-228
223-225
228-229
>300
83
94
70
73
70
88
—
—
—
—
—
8a
8b
8c
9
C14H17N5O3S
C13H14ClN5O3S
C15H18N6O4S
C8H10KN5OS2
10.00
9.55
19.31
19.69
8.11
8.47
22.00
21.69
TABLE 2. 1H NMR Spectra of Compounds 1-9
Com-
pound
Chemical shifts, δ, ppm (J, Hz)
1
3.35 [6Н, s, N(СН3)2]; 3.65 [9Н, s, N+(СН3)3]; 3.82 (3H, s, OCH3);
4.08 (2Н, s, NCH2CO); 9.78 (1H, br. s, NH)
2
3.16 and 3.20 [both 3Н, s, N(CH3)2]; 3.65 (2H, t, J = 6.7, CH2Cl); 3.78 (3H, s, OCH3);
4.05 (2Н, s, NCH2CO); 4.27 (2H, t, J = 6.7, OCH2); 9.62 (1H, br. s, NH)
3
3.22 and 3.24 [both 3Н, s, N(СН3)2]; 3.75 (3Н, s, ОСН3);
3.90-4.12 (4Н, m, NCH2CH2N); 4.37 (2Н, s, NCH2CO)
4
3.10 and 3.15 [both 3Н, s, N(CH3)2]; 3.63-3.95 (4Н, m, NCH2CH2N);
3.98 (2Н, s, NCH2CO); 4.10 (2H, v. br. s, NH2); 9.28 (1H, br. s, NH)
6a
3.20 and 3.28 [both 3Н, s, N(СН3)2]; 3.90-4.12 (4H, m, NCH2CH2N);
7.13-7.50 (5H, m, C6H5); 10.52 (1H, s, NH)
6b
6c
6d
7
3.22 and 3.28 [both 3Н, s, N(СН3)2]; 3.92-4.13 (4H, m, NCH2CH2N);
7.27-7.54 (4H, m, C6H4); 10.58 (1H, s, NH)
3.16 and 3.18 [both 3Н, s, N(СН3)2]; 3.70-4.08 (4H, m, NCH2CH2N);
7.25-7.50 (4H, m, C6H4); 9.38 (1H, br. s, NH)
3.18 and 3.22 [both 3Н, s, N(СН3)2]; 3.90-4.05 (4H, m, NCH2CH2N);
7.30-7.58 (4H, m, C6H3); 10.12 (1H, s, NH)
2.58 (3H, s, COCH3); 3.15 and 3.17 [both 3Н, s, N(СН3)2];
3.85-4.00 (4H, m, NCH2CH2N)
8a
8b
8c
9
2.47 (3H, s, CH3); 3.08 and 3.17 [both 3Н, s, N(СН3)2]; 3.85-4.18 (4H, m, NCH2CH2N);
7.35-7.97 (4H, m, C6H4)
3.12 and 3.18 [both 3Н, s, N(СН3)2]; 3.82-4.15 (4H, m, NCH2CH2N);
7.40-8.00 (4H, m, C6H4)
2.27 (3H, s, COCH3); 3.15 and 3.20 [both 3Н, s, N(СН3)2];
3.80-4.12 (4H, m, NCH2CH2N); 7.48-8.10 (4H, m, C6H4)
3.12 and 3.17 [both 3Н, s, N(СН3)2]; 3.80-4.05 (4H, m, NCH2CH2N)
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The corresponding potassium dithiocarbamate 9 was synthesized as a compound with potential
fungicidal activity.
1
In the H NMR spectra of the synthesized compounds 6-9 signals were displayed corresponding to the
protons of the 8-substituent, in place of the signal of the NH group proton in compound 5 (Table 2).
EXPERIMENTAL
1
The H NMR spectra were taken on a Mercury-300 (300 MHz) NMR spectrometer in DMSO-d6,
internal standard was TMS. TLC was carried out on Silufol UV-254 plates in the system acetone–hexane, 1:2.
(2-Dimethylamino-6-methoxycarbonylmethylamino-sym-triazin-4-yl)trimethylammonium Chloride
(1) was obtained by the procedure described in [2]. Yield was 92%; mp 155-156°C. Found, %: Cl 11.37;
N 27.80. C11H21ClN6O2. Calculated, %: Cl 11.65; N 27.58.
6-(2-Chloroethoxy)-2-dimethylamino-4-methoxycarbonylmethylamino-sym-triazine (2). Ethylene
chlorohydrin (3.2 g, 40 mmol) was added to a suspension of 84% KOH (powder) (0.7 g, 10 mmol) in dry CHCl3
(10 ml) at 0°C, then compound 1 (3.0 g, 10 mmol) was added in portions. The reaction mixture was stirred for
30 min at 0°C, then for 4 h at 20°C. The mixture was filtered, the filtrate evaporated, the residue was treated
with water (10 ml), and compound 2 was filtered off.
(2-Dimethylamino-4-oxo-6,7-dihydro-4H-imidazo[1,2-a]-1,3,5-triazin-8-yl)acetic Acid Methyl
Ester (3). A. A solution of compound 2 (1.45 g, 5 mmol) in absolute benzene (15 ml) was boiled for 10 h. The
benzene was decanted, and the glassy mass was triturated sequentially with hexane and with petroleum ether,
filtered, and rapidly transferred to a desiccator over H2SO4. Compound 3 hydrochloride (1.0 g, 69%) was
obtained of decomposition point 96-97°C. A suspension of the latter in dry acetone (10 ml) was then neutralized
with K2CO3 powder (0.24 g, 1.7 mmol). After 3 h the KCl was filtered off, and compound 3 was isolated (0.6 g,
69%) from the filtrate as a readily water-soluble viscous liquid.
B. Compound 5 (0.9 g, 5 mmol) was added to a suspension of 84% KOH powder (0.35 g, 5 mmol) in
DMF (10 ml) and the mixture was stirred for 2 h at 20°C. Methyl bromoacetate (0.8 g, 5 mmol) was added and
the mixture heated for 6 h at 75-80°C, cooled, the KBr filtered off, and DMF was distilled from the filtrate at
68-70°C (40 mm Hg), the residue was triturated with hexane, and the latter decanted. Compound 3 (1.1 g, 88%)
was obtained in the residue as a viscous liquid, readily soluble in water.
(2-Dimethylamino-4-oxo-6,7-dihydro-4H-imidazo[1,2-a]-1,3,5-triazin-8-yl)acetic Acid Hydrazide
(4). Hydrazine hydrate (63%, 2 ml) was added to a solution of compound 3 (0.76 g, 3 mmol) in water (2 ml) and
the mixture maintained at 20°C during 3 h. Compound 4 was filtered off and dried in the air.
2-Dimethylamino-7,8-dihydro-6H-imidazo[1,2-a]-1,3,5-triazin-4-one (5) was obtained by the method
1
described in [6]. H NMR spectrum, δ, ppm: 3.08 [6H, s, N(CH3)2]; 3.57-3.95 (4H, m, NCH2CH2N); 8.10 (1H,
br. s, NH).
(2-Dimethylamino-4-oxo-6,7-dihydro-4H-imidazo[1,2-a]-1,3,5-triazin-8-yl)carboxylic Acid Phenyl-
amide (6a). A mixture of compound 1 (1.8 g, 10 mmol) and freshly distilled phenyl isocyanate (1.19 g,
10 mmol) in absolute toluene (10 ml) was boiled in the presence of catalytic quantities of pyridine for 5 h. The
precipitate of compound 6a was filtered off and washed on the filter with benzene (10 ml).
Compounds 6b-d were obtained analogously.
8-Acetyl-2-dimethylamino-7,8-dihydro-6H-imidazo[1,2-a]-1,3,5-triazin-4-one (7). A mixture of
compound 5 (1.8 g, 10 mmol) in acetic anhydride (10 ml) was boiled for 8 h. The solution was evaporated, the
solid triturated under hexane, then boiled with petroleum ether, and solid compound 7, which dissolved well in
water, was filtered off.
2-Dimethylamino-8-tosyl-7,8-dihydro-6H-imidazo[1,2-a]-1,3,5-triazin-4-one (8a). A suspension of
compound 5 (1.8 g, 10 mmol) and 84% KOH powder (0.7 g, 10 mmol) in DMF (10 ml) was stirred for 2 h at
994

20°C. p-Toluenesulfonyl chloride (1.9 g, 10 mmol) was then added and the reaction mixture heated at 70-80°C
for 4 h. The KCl was filtered off, DMF was distilled from the filtrate at 70-72°C (40 mm Hg), the residue was
boiled with benzene, and compound 8a was filtered off.
Compounds 8b,c were obtained analogously.
Potassium Salt of 2-Dimethylamino-4-oxo-6,7-dihydro-4H-imidazo[1,2-a]-1,3,5-triazine-8-di-
thiocarbonic Acid (9). 84% KOH powder (0.7 g, 10 mmol) was added to compound 5 (1.8 g, 10 mmol) in
absolute ethanol (10 ml) and the mixture was stirred for 30 min. Carbon disulfide (0.8 g, 10 mmol) was added
dropwise at 0°C and the reaction mixture was maintained at 20°C for 24 h. The solid compound 9 was filtered
off, and washed on the filter with absolute ether (10 ml).
REFERENCES
1.
2.
V. V. Dovlatyan, Khim. Geterotsikl. Soedin., 435 (1996). [Chem. Heterocycl. Comp., 32, 375 (1996)].
V. V. Dovlatyan, K. A. Eliazyan, and L. G. Agadzhanyan, Khim. Geterotsikl. Soedin., 262 (1977).
[Chem. Heterocycl. Comp., 13, 210 (1977)].
3.
N. N. Mel′nikov, Chemistry and Technology of Pesticides [in Russian], Khimiya, Moscow (1974),
665 pp.
4.
5.
6.
R. K. Robins, J. B. Allen, G. R. Rewenkaz, US Patent 246408 (1980); Chem. Abs., 95, 25544 (1981).
J. B. Holtwick and N. J. Leonard, J. Org. Chem., 46, 3681 (1981).
K. A. Eliazyan, A. M. Akopyan, V. A. Pivazyan, A. G. Akopyan, and V. V. Dovlatyan, Khim.
Geterotsikl. Soedin., 228 (1992). [Chem. Heterocycl. Comp., 28, 188 (1992)].
995