Synthesis of heterobicyclic nitrogen compounds as molluscicide agents derived from 6-methyl-5-styryl-1,2,4-triazin-3-thiol: Part I

Article abstract of DOI:10.1080/10426500307944

Some new heterocyclic nitrogen compounds 1-14 have been synthesized from cyclization of 5-styryl-3-mercapto-6-methyl-1,2,4-triazines 1 with active methylene and/or nitrogen compounds and were evaluated as molluscicidal agents. Significant molluscicidal activities for some of the products towards Biomophalaria Alexandrina snails were observed.

Full text of DOI:10.1080/10426500307944

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Phosphorus, Sulfur, and Silicon and the Related
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Synthesis of Heterobicyclic Nitrogen Compounds
as Molluscicide Agents Derived from 6-Methyl-5-
styryl-1,2,4-triazin-3-thiol: Part I
T. M. Abdel-Rahman a , A. A. Shalaby b & I. F. Nassar a
a Faculty of Specific Education, Ain Shams University, Cairo, Egypt
b Faculty of Science, Ain Shams University, Cairo, Egypt
Published online: 27 Oct 2010.
To cite this article: T. M. Abdel-Rahman , A. A. Shalaby & I. F. Nassar (2003): Synthesis of Heterobicyclic Nitrogen Compounds
as Molluscicide Agents Derived from 6-Methyl-5-styryl-1,2,4-triazin-3-thiol: Part I, Phosphorus, Sulfur, and Silicon and the
Related Elements, 178:2, 279-292
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:279–292
C
Copyright 2003 Taylor & Francis
1042-6507/03 $12.00 + .00
DOI: 10.1080/10426500390170390
SYNTHESIS OF HETEROBICYCLIC NITROGEN
COMPOUNDS AS MOLLUSCICIDE AGENTS
DERIVED FROM 6-METHYL-5-STYRYL-
1,2,4-TRIAZIN-3-THIOL: PART I
T. M. Abdel-Rahman,a A. A. Shalaby,b and I. F. Nassara
Faculty of Specific Education,a Faculty of Science,b
Ain Shams University, Cairo, Egypt
(Received November 8, 2001; accepted March 19, 2002)
Some new heterocyclic nitrogen compounds 1–14 have been synthesized
from cyclization of 5-styryl-3-mercapto-6-methyl-1,2,4-triazines 1 with
active methylene and/or nitrogen compounds and were evaluated as
molluscicidal agents. Significant molluscicidal activities for some of the
products towards Biomophalaria Alexandrina snails were observed.
Keywords: Molluscicide activity; substituted 1,2,4-triazines
INTRODUCTION
The structural diversity and biological significance of 1,2,4-triazines
have received much attention owing to the wide range of biological ac-
8
tivities of these compounds.1 In the present work we describe a con-
venient one-pot procedure for the synthesis of some new heterobicyclic
nitrogen systems bearing a 1,2,4-triazine moiety. The molluscicide ac-
tivities of some of these compounds also are described.
RESULTS AND DISCUSSION
The required 6-methyl-5-[substituted styryl]-2H-[1,2,4]triazine-3-
thiones(1a–j) were obtained from condensation of 5,6-dimethyl-1,2,4-
triazin-3(2H)thione with various aldehydes in glacial acetic acid with
fused sodium acetate (Scheme 1).9,10
Refluxing compound 1j with MeOH-HCHO and/or MeOH-HCHO
in the presence of piperidine led to the formation of the
Address correspondence to T. M. Abdel-Rahman, Faculty of Specific Education, Ain
Shams University, Cairo, Egypt. E-mail: taha mahmood48@hotmail.com
279

280
T. M. Abdel-Rahman et al.
N-hydroxymethylderivative 2 and the N-Mannich’s base compound
3 respectively (Scheme 1). On the other hand, refluxing 1b–f with
monochloroacetic acid in DMF produced 3-[Carboxymethylthio]-6-
methyl-5-[substituted styryl][1,2,4]triazines (4a–e) (Scheme 1).
SCHEME 1
The chemistry of pyrimidines has received much attention in re-
14
cent years11
due to the unique physical and chemical proper-
ties of such derivatives, which have gained wide applications in bi-
ological activity. This together with our interest in the synthesis of
1,2,4-triazine derivatives prompted us to investigate the synthesis

Synthesis of Heterobicyclic Nitrogen Compounds
281
of heterobicyclic systems that combind both pyrimidine and 1,2,4-
triazines. Thus, the reactions of compounds 1c,g with malonic acid
in the presence of sodium ethoxide gave the dibasic acids 5a,b
which upon heterocyclization by refluxing with thiourea in methanol
furnished 6-methyl-5-[substituted styryl]-3-[4,6-dioxo-2-thioxo-1,3,5-
trihydropyrimidin-5-yl][1,2,4]triazines (6a,b) (Scheme 2).
SCHEME 2
The target heterobicyclic nitrogen systems 6-methyl-5-[substituted
styryl]-3-[N-substituted thiourea][1,2,4] triazines (7a–h) 6-methyl-
5-[substituted styryl]-3-[5-dihydro-4,6-dioxo-1-substituted-2-thioxopy-
rimidin-3-yl][1,2,4]triazines (8a–h) and/or 4,7-dimethyl-8-[2-ethenyl

282
T. M. Abdel-Rahman et al.
furan]-2-thioxo-1,3,5 triazino[5,6-b][1,2,4]triazine (9) have been syn-
thesized from the reaction of 1b,d,f,g with thiourea or acetyl thiourea15
to give the N,N0-disubstituted thioureas (7a–h). Upon cyclization of
these compounds with malonic acid15 in the presence of glacial acetic
acid and/or refluxing compound 7d with glacial acetic acid with fused
sodium acetate, the compounds 8a–h and 9 were obtained respectively
(Scheme 2).
Similarly, reaction of compound 1b,d,f with acetamidine hydrochlo-
ride via loss of H2S, afforded the amidines 10a–c which on reflux-
ing with malonic acid and a few drops of acetyl chloride yielded
6-methyl-5-[substituted styryl]-3-[5-dihydro-4,6-dioxo-2-methylpyri-
midin-3-yl][1,2,4]triazines (11a–c) (Scheme 3).
SCHEME 3
Amination of compound 1b,d using cyanamide yielded 3-cyano-
amino-6-methyl-5-[substituted styryl][1,2,4]triazines (12a,b), which
on addition with hydrazine hydrate produced the N4-substituted

Synthesis of Heterobicyclic Nitrogen Compounds
283
aminoguanidines (13a,b). Ring closure of 13a,b with ethyl pyruvate16
led to the formation of 3-[3-ethylpropionate imino]-6-methyl-5-
oxo-[1,2,4]triazin-4-yl)-6-methyl-5-[substituted styryl][1,2,4]triazines
(14a,b) (Scheme 3).
MOLLUSCICIDE EVALUATION
A wide variety of chemical compounds containing N C S moiety have
been found to be biologicaly active.17,18 Cyclic structure containing the
22
N C S group have a range of biological activities.19
On the other
hand, several enzymes contain thiol groups, often in the apoenzyme
or protein part of the molecule, which is essential for their activity.
Consequently any reagent that reacts readily with the thiol group of
such systems can destroy their function and may inhibit the reactivity
of such enzymes.
The compounds listed in Table I were tested for their effect on some
snails, especially Biomphalaria alexandrina (average shell diameter
6–8 mm) the intermediate host of Schistosoma mausoni in Giza gov-
ernestate, that were not treated with molluscicides. The snails were
adapted to laboratory conditions three weeks before being used in tox-
icity tests to be sure that they were strong and healthy. Snails were
kept in a plastic aguaria filled with dechlorinated tap water at room
temperature, 25–27 C. Dried lettuce leaves were added daily and the
water was changed weekly.
TABLE I The Molluscicidal Acivity of Some Prepared
Compounds Against Biomphalaria alexandrina Snails
Mortality % of snails at concentration
Compd.
100 ppm
50 ppm
25 ppm
1d
1f
1g
1i
1j
2
100
0
0
80
0
0
0
0
50
100
0
100
0
0
20
0
0
0
0
0
30
0
50
0
0
0
0
0
0
0
0
0
0
0
0
0
3
4b
7b
7g
10b
11c
12b
14a
0
0
0
0
0
0

284
T. M. Abdel-Rahman et al.
Stock solutions of the investigated compounds (500 ppm) were dis-
solved in the least amount of ethanol and diluted with dechlorinated
tap water on the basis of weight/volume series of dilutions of each com-
pound were prepared.
The number of snails in each experiment and control was ten. The
exposure time was 24 h followed by 24 h as recovery period. Standard
procedures were followed according to the methods recommended by
WHO.23,24 Table I indicates that under the employed experimental con-
ditions the quantitative structure activity relationship studies of these
compounds showed that:
1. At concentration 25 ppm only one compound 1d showed an antis-
nail activity which could be attributed to the p-dimethylaminostyryl
moiety.
2. At concentration 50 ppm the compounds 1d, 1i, and 7g showed an
antisnail activity in the order 1d > 7g > 1i, which was attributed
to the presence of the p-dimethylamino 1d, -naphthol (7g) and 2,4-
dichloro phenyl (1i) moieties.
3. At concentration 100 ppm the compounds 1d, 1i, 7b and 7g showed
an antisnail activity in the order 1d = 7g > 7b > 1i.
Conclusion: Only compounds 1d, 1i, 7b, and 7g showed antisnail
activity.
EXPERIMENTAL
The reported m.p. were uncorrected. IR spectra in KBr were recorded on
a Perkin-Elmer 293 FT spectrophotometer (˜ in cm 1), UV absorption
spectra in DMF were recorded on a Perkin-Elmer, Lambda 4B contro-
lar accessory interface, UV-VIS spectrophotometer ( in nm), 1H-NMR
spectra were recorded on a EM NMR spectrometer 200 MHz PMR us-
ing DMSO as a solvent and TMS as an internal reference (chemical
shifts in ppm), and mass spectra were recorded on a gas chromato-
graphic GCMS qp 1000cx Shimadzu instrument at 70 eV. Compound
5,6-dimethyl-1,2,4-triazin-3(2H) thione was prepared following a re-
ported procedure.11 The physical data of the synthesized compounds
are given in (Table II).
6-Methyl-5-propenyl-2H-[1,2,4]triazin-3-thione (1a)
A mixture of 5,6-dimethyl-1,2,4-triazin-3(2H) thione (0.01 mmol) and
acetaldehyde (0.01 mmol) in AcOH (20 ml)-AcONa (5 g) was refluxed for
2 h and poured onto ice. The solid obtained was filtered and crystallized
to give 1a (Table II).

Synthesis of Heterobicyclic Nitrogen Compounds
285
TABLE II Characterizing Data of the Prepared Compounds
Molecular
formula
(mol. wt.)
Analysis % calculated (found)
Cl S
m.p.
C
Compd. Solvent (yield)
C
H
N
1a
1b
1c
1d
1e
1f
AcOH
EtOH
MeOH
115–116
(55)
276–277
(40)
190–191
(50)
172–173
(55)
C7H9N3S
(167.24)
12H10N3ClS
(263.75)
C13H13N3S
(243.33)
C14H16N4S
(272.38)
12H10N4O2S
(274.31)
C10H9N3OS
(219.92)
C16H13N3OS
(295.97)
50.28 5.42
(50.04) (5.38)
54.65 3.82 13.44 15.93 12.16
(54.37) (3.66) (13.08) (15.48) (11.87)
25.13 19.17
(24.96) (18.81)
C
64.17 5.38
(65.09) (5.17)
61.74 5.92
(61.88) (6.01)
52.55 3.68
(52.98) (3.64)
54.62 4.42
(54.47) (4.38)
64.93 4.43
(64.91) (4.28)
56.71 4.76
(56.45) (4.81)
17.27 13.18
(17.08) (13.51)
20.57 11.77
(20.83) (11.47)
20.42 11.69
(20.61) (11.52)
19.11 14.58
(19.23) (14.52)
14.20 10.83
(14.17) (10.70)
15.26 11.65
(15.09) (11.51)
Pet.
Ether
Benzene 180–181
(52)
Benzene 207–208
(45)
C
1g
1h
1i
AcOH
EtOH
EtOH
EtOH
EtOH
EtOH
AcOH
EtOH
AcOH
AcOH
AcOH
276–278
(40)
213–215
(50)
175–176
(55)
214–215 C15H17N3O3S
(48)
180–181
(30)
196–198
(22)
C
13H13N3O2S
(275.34)
12H9N3Cl2S
(298.85)
C
48.23 3.25 23.97 14.20 10.84
(48.20) (3.38) (23.73) (13.33) (10.71)
1j
56.41 5.37
(56.25) (5.42)
55.00 5.48
(54.83) (5.35)
60.55 6.78
(60.72) (6.65)
13.16 10.04
(13.27) (9.92)
(319.39)
16H19N3O4S
(349.42)
21H28N4O3S
(416.55)
2
C
C
12.03
(11.97) (8.96)
13.45 7.70
(13.23) (7.33)
9.96
(52.17) (3.87) (10.90) (12.89) (10.01)
9.18
3
4a
4b
4c
4d
4e
5a
5b
6a
6b
7a
270–271 C14H12N3O2ClS 52.26 3.76 11.02 13.06
(28)
256–258
(25)
(321.79)
15H15N3O2S
(301.38)
C
59.78 5.02
(59.66) (4.96)
58.16 5.49
(58.22) (5.37)
50.60 3.64
(50.54) (3.56)
51.98 4.00
(51.87) (4.11)
61.34 4.83
(61.76) (4.72)
62.46 4.14
(62.35) (3.97)
57.78 4.28
(57.66) (4.17)
59.25 3.73
(59.15) (3.81)
13.94 10.64
(13.88) (10.50)
280–281 C16H18N4O2S
16.99
(17.07) (9.53)
16.86 9.65
9.70
(30)
190–192
(35)
230–231
(33)
220–222
(32)
271–272
(22)
(330.42)
14H12N4O4S
(332.35)
12H11N3O3S
(277.31)
C16H15N3O4
(313.32)
19H15N3O5
(365.36)
C
C
(16.78) (9.55)
15.15 11.56
(15.22) (11.73)
13.41
(13.33)
11.50
Pet.
Eter
EtOH
C
(11.69)
Pet.
Ether
210–212 C17H15N5O2S
(21) (353.41)
19.82
(20.01) (8.93)
17.27 7.91
(16.96) (7.87)
9.07
Benzene 260–261 C20H15N5O3S
(31) (405.45)
190–192 C13H12N5ClS
(33) (305.80)
EtOH
51.06 3.96 11.59 22.90 10.49
(50.98) (4.03) (11.52) (23.07) (10.33)
(Continued on next page)

286
T. M. Abdel-Rahman et al.
TABLE II Characterizing Data of the Prepared Compounds (Continued)
Molecular
formula
(mol. wt.)
Analysis % calculated (found)
Cl
m.p.
C
Compd. Solvent (yield)
C
H
N
S
7b
7c
Benzene 240–242 C15H14N5OSCI 51.80 4.06 10.19 20.13
9.22
(30)
236–238
(37)
265–266 C13H13N5O2S
(35)
(347.834)
11H11N5OS
(261.311)
(51.66) (4.21) (10.44) (20.33) (9.04)
EtOH
EtOH
C
50.56 4.24
(51.00) (4.06)
51.48 4.32
(51.33) (4.27)
57.30 5.77
(57.09) (5.56)
57.28 5.66
(57.17) (5.71)
60.52 4.48
(60.34) (4.38)
60.15 4.52
(60.28) (4.43)
26.80 12.27
(26.72) (11.97)
23.09 10.57
(22.95) (10.5)
26.73 10.20
(26.61) (10.03)
7d
7e
(303.35)
C15H18N6S
(314.421)
Benzene 280–281
(20)
285–286
(20)
Benzene 260–261
(24)
7f
DMF
C
17H20N6OS
23.58
(23.42) (8.94)
20.76 9.50
(21.00) (9.41)
18.46 8.45
(18.40) (8.32)
9.48 18.73 8.58
(51.52) (3.13) (9.27) (18.87) (8.32)
18H14N5O3ClS 51.95 3.39 8.52 16.90 7.71
(416.17) (51.79) (3.23) (8.37) (16.67) (7.63)
9.00
(356.46)
7g
C17H15N5OS
(337.412)
7h
8a
Pet.
Ether
EtOH
220–221 C19H17N5O2S
(32)
250–252
(30)
(379.45)
C
16H12N5O2ClS 51.41 3.24
(373.83)
8b
8c
Benzene 286–287
(31)
C
EtOH
275–277 C14H11N5O3S
51.06 3.37
(51.56) (3.52)
51.75 3.53
(52.00) (3.48)
56.53 4.74
(56.46) (4.87)
56.59 4.75
(59.32) (4.67)
59.05 3.83
(58.89) (3.72)
59.25 3.73
(59.06) (3.62)
54.72 3.89
(54.38) (4.01)
21.26
(21.38) (9.47)
18.86 8.63
(18.71) (8.59)
21.97 8.38
(22.12) (8.25)
19.80 7.55
(20.03) (7.32)
15.65 7.17
(15.44) (6.92)
17.27 7.91
9.74
(24)
270–272
(48)
265–266
(25)
(329.35)
16H13N5O4S
(371.382)
18H18N6O2S
(382.45)
8d
8e
EtOH
C
C
Pet.
Ether
Pet.
Ether
EtOH
8f
210–212 C20H20N6O3S
(22)
286–287
(32)
(424.49)
22H17N5O4S
(447.48)
8g
C
8h
9
EtOH
EtOH
EtOH
246–248 C20H15N5O3S
(36)
260–261
(21)
(405.45)
13H11N5OS
(285.34)
(17.03) (8.01)
24.54 11.24
(24.35) (11.43)
C
10a
10b
10c
11a
11b
11c
270–271
(45)
C
14H14N5Cl
(287.76)
58.44 4.90 12.32 24.34
(58.63) (4.72) (11.92) (24.55)
Pet.
Ether
AcOH
255–257
(40)
296–297
(31)
C16H20N6
(296.38)
64.84 6.80
(64.72) (6.88)
59.25 5.39
(59.12) (5.23)
28.36
(28.17)
28.79
C
12H13N5O
(243.28)
(28.64)
MeOH
230–231 C17H14N5O2Cl 57.39 3.97
9.97 19.68
(32)
133–135
(50)
280–282
(55)
(355.79)
C19H20N6O2
(364.42)
C15H13N5O3
(311.31)
(57.22) (3.81) (9.53) (19.52)
Pet.
Ether
AcOH
62.63 5.53
(62.70) (5.38)
57.88 4.21
(57.75) (4.09)
23.06
(23.30)
22.50
(22.38)
(Continued)

Synthesis of Heterobicyclic Nitrogen Compounds
287
TABLE II Characterizing Data of the Prepared Compounds (Continued)
Molecular
formula
Analysis % calculated (found)
m.p.
C
Compd. Solvent
(yield)
(mol. wt.)
C
H
Cl
N
S
12a
12b
13a
13b
14a
14b
DMF
235–236
(53)
C13H10N5Cl
(271.72)
57.47
3.71
13.05
25.77
(57.29) (3.58) (12.86) (25.91)
Pet. Ether 230–231
(54)
C15H16N6
64.27
(63.89) (5.81)
51.41 4.65
5.75
29.98
(29.59)
32.28
(280.34)
C13H14N7Cl
(303.76)
C15H20N8
(312.39)
DMF
EtOH
DMF
247–249
(55)
185–186
(53)
230–231
(35)
11.67
(51.50) (4.54) (11.43) (32.09)
57.68
(57.57) (6.53)
4.65
(55.72) (4.51)
59.73 5.67
(60.01) (5.59)
6.45
35.87
(35.78)
21.55
C21H20N7O3Cl 55.45
7.79
(7.70) (21.95)
24.23
(454.91)
C23H26N8O3
(462.52)
Pet. Ether 190–191
(33)
(24.18)
6-Methyl-5-[substituted styryl]-2H-[1,2,4]triazin-
3-thiones (1b–j)
A mixture of 5,6-dimethyl-1,2,4-triazin-3(2H) thione (0.01 mmol) and
an aromatic aldehyde such as acetaldehyde, 4-chlorobenzaldehyde,
4-methylbenzaldehyde, 4-(dimethylamino)benzaldehyde, 3-nitrobenza-
ldehyde, furfural, 2-hydroxynaphthaldehyde, vanilline, 2,4-dichloro-
benzaldehyde, and 3,4,5-trimethoxybenzaldehyde (0.01 mmol) in AcOH
(20 ml)-AcONa (5 g) was refluxed for 2 h, cooled, and poured onto
ice. The resultant solids were filtered and crystallized to give (1b–j)
(Table II). UV (1i): 245 (3.00). IR (1e): 3102 (NH); 3061 (aromatic CH);
2981 (aliphatic CH); 1654 (CH CH); 1593 (C N); 1526 (assy. NO2);
1474, 1459 (def. Me); 1166 (C S); 810, 735 (Phenyl group). (1j); 3200
(NH); 3050 (aromatic CH); 2880 (aliphatic CH); 1640 (CH CH); 1610
(C N); 1480 (defm. CH3); 1350 (NCSN); 1160 (C-S); 1040 (C O C); 800
(aryl group). 1H-NMR (1j): 1.5 (s, 3H, CH3); 4.5 (s, 9H, 3OCH3); 7.1–7.3
(dv, 2H, CH CH); 7.5–7.7 (m, 2H, aromatic protons); 8.7 (s, 1H, NH).
MS (Int.%) (1a): m/z 167.24 (8.44); 152 (19.01); 138.9 (100); 124 (11.17);
113 (17.33); 54 (22.05). (1b): m/z 263.75; 116 (35.38); 143 (100); (1f): m/z
219.916; 132 (7.48); 116 (48.38); 99 (6.67); 60 (100) (1j): m/z 319.39; 138
(9.39) 112 (6.11) and 60 (100).
2-Hydroxymethyl-6-methyl-5-[3,4,5-
trimethoxystyryl][1,2,4]triazin-3-thione (2)
A mixture of 1j (0.01 mmol) and formaldehyde (0.01 mmol) in methanol
(20 ml) was refluxed for 4 h, cooled, and poured onto ice. The formed

288
T. M. Abdel-Rahman et al.
solid was filtered and crystallized to give 2 (Table II). IR: 3450 (OH);
3100–3080 (aromatic CH); 2980 (aliphatic CH); 1610 (CH CH); 1480–
1440 (def. CH3); 1150 (C-S); 1030 (C O C); 830 (aryl group). 1H-NMR:
2.5 (s, 2H, CH2); 3.7–4.0 (s, 9H, 3OCH3), 7.35–7.85 (m, 4H, styryl and
aromatic protons); 8.6 (s, 1H, OH).
6-Methyl-2-[piperidin-1-ylmethyl]-5-[3,4,5-
trimethoxystyryl]-2H-[1,2,4]triazin-3-thione (3)
A mixture of 1j (0.01 mmol) and formaldehyde (0.01 mmol) in methanol
(20 ml) and piperidine (0.01 mmol) was refluxed for 4 h, cooled, and
poured onto ice. The resultant solid was filtered and crystallized to give
3 (Table II). 1H-NMR. 1.5 (s, 3H, CH3); 1.9–2.2 (m, 10H, piperidine); 2.5
(s, 2H, CH2); 3.5 (s, 3H, OCH3); 7.6–7.9 (m, 2H, CH CH, 2H, aromatic).
MS (Int.%): m/z 416.55 (0.04); 390.2 (36.98); 388.2 (100); 373.1 (54.48);
329 (12.87); 195 (11.23).
3-[Carboxymethylthio]-6-methyl-5-[substituted
styryl][1,2,4]triazines (4a--e)
A mixture of 1b, 1c, 1d, 1e, 1f (0.01 mmol) and monochloroacetic acid
(0.01 mmol) in DMF (20 ml) was refluxed for 2 h); cooled, and poured
onto ice. The solid obtained was filtered and crystallized to give 4a–e
1
(Table II). H-NMR (4a): 1.5 (s, 3H, CH3); 2.2 (s, 2H, CH2); 7.2–7.4
(dv, 2H, CH CH); 7.6–7.8 (m, 4H, aromatic protons); 10.5 (s, 1H, OH).
2-(2,3-Dihydro-6-methyl-5-[substituted
styryl][1,2,4]triazin-3-yl)malonic acid (5a,b)
A mixture of 1c,1g (0.01 mmol) and malonic acid (0.01 mmol) in DMF
(20 ml) was refluxed for 2 h, cooled, and poured onto ice. The solid
obtained was filtered and crystallized to give 5a,b (Table II). IR (5a):
3446 (OH); 3469 (OH); 3010 (aromatic CH); 2923 (aliphatic CH); 1697
(C O); 1606 (CH CH); 1456 (def. CH3); 806 (aryl group). 1H-NMR (5a):
1.2 (s, 3H, CH3); 1.5 (s, 3H, CH3); 4.5 (s, 2H, CH CH); 7.4–7.6 (d, 2H,
CH CH); 7.7–7.9 (m, 4H, aromatic protons); 8.5–8.9 (s, 1H, OH).
6-Methyl-5-[substituted styryl]-3-[4,6-dioxo-2-thioxo-
1,3,5-trihydroPyrimidin-5-yl][1,2,4]triazines (6a,b)
Compound 5a or 5b (0.01 mmol) and thiourea (0.01 mmol) in AcOH
(20 ml) was refluxed for 4 h, cooled, and poured onto ice. The solid

Synthesis of Heterobicyclic Nitrogen Compounds
289
obtained was filtered and crystallized to give 6a or b (Table II). UV
(6b): 305 (3.0); 290 (3.8) nm. IR (6b): 3451, 3444 (OH); 3168 (NH);
3016 (aromatic CH); 2958 (aliphatic CH); 1606 (CH CH); 1494 (def.
1
Me); 1338 (NCSN); 1160 (C-S); 804, 767 (aryl group) cm 1. H-NMR
(6b): 2.1 (s, 3H, CH3); 3.5 (s, 1H, CH); 7.1–7.9 (m, 6H, aryl and 2H,
CH CH protons); 9.8 (s, H, OH) and 12.6 (s, 2H, NH). MS (Int.%)
(6b): m/z 405.45; 341.1 (36.58); 340.1 (100); 170 (36.42); 154 (3.02); 115
(9.21).
6-Methyl-5-[substituted styryl]-3-[N-substituted
thiourea][1,2,4]triazines (7a–h)
A mixture of 1b, 1d, 1f, or 1g (0.01 mmol) and thiourea or acetyl
thiourea (0.01 mmol) in DMF (20 ml) was refluxed for 2 h, cooled, and
poured onto ice. The solid obtained was filtered and crystallized to give
7a–h (Table II). IR (7h) 3450 (OH); 3150 (NH); 3050 (aromatic CH);
2950 aliphatic CH); 1650 (COMe); 1500–1450 (def. Me); 1380 (NCSN);
1160 (C S); 830, 780 (Phenyl groups). 1H-NMR (7h): 1.2 (s, 3H, CH3);
2.5 (s, 3H, CH3CO); 7.5–7.9 (m, 6H, aromatic; 2H, CH CH); 9.5 (s, 1H,
OH); 12.6, 13 (s, 1H, NH, NH).
6-Methyl-5-[substituted styryl]-3-[5-dihydro-4,6,-dioxo-1-
substituted-2-thioxo-pyrimidin-3-yl[1,2,4]triazines
(8a–h)
A mixture of 7a–h (0.01 mmol) and malonic acid (0.01 mmol) in AcOH
(20 ml) was refluxed for 4 h, cooled, and poured onto ice. The solid was
filtered and crystallized to give 8a–h (Table II). IR (8b): 3414 (OH); 3100
(aromatic CH); 2922, 2854 (aliphatic CH); 1725 (C O); 1609 (C C);
1
1463 (def. Me); 1166 (C-S), 780 (aryl group). H-NMR (8b): 3.2 (s, 3H,
CH3CO); 2.4–4.6 (s, 6H, 2CH3); 7.2–7.8 (m, 6H, CH CH, and aromatic
protons); 12.5 (s, 1H, OH).
4,7-Dimethyl-8-[2-ethenyl furan]-2-thioxo-1,3,5 triazino
[5,6-b][1,2,4]triazine (9)
A mixture of 7d (0.01 mmol) and gl.AcOH (20 ml) fused AcONa (1 g)
was refluxed for 2 h, cooled, and poured onto ice. The resultant solid
was filtered and crystallized to give 9 (Table II). MS (Int.%): m/z,
285.34; 167 (17.26); 149 (48.03); 93 (8.11); 71 (66.16); 57 (100); 55
(59.01). 1H-NMR 1.1, 1.5 (s, 6H, 2CH3); 7.6–8 (m, 2H, CH CH, 4H furyl
protons).

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N-(6-Methyl-5-[substituted styryl][1,2,4]triazin-
3yl)acetamidines (10a–c)
A mixture of 1b, 1d, or 1f (0.01 mmol) and acetamidine (0.01 mmol)
in DMF (20 ml) was refluxed for 2 h, cooled, and poured onto ice. The
solid obtained was filtered and crystallized to give 10a–c (Table II). IR
(10b): 3164 (NH); 2926 (aliphatic CH); 1603 (CH CH); 1535 (C N);
1
1475; 1442 (def. Me); 1364 (NCN); 819; 764 (Phenyl group). H-NMR
(10b): 0.9, 1.2, 1.6 (s, 9H, 3CH3); 7.4–7.8 (m, 6H, 2H, CH CH, 4H,
aromatic protons); 8.5, 11.5 (s, 2H, NH , NH).
6-Methyl-5-[substituted styryl]-3-[5-dihydro-4,6-dioxo-
2-methylPyrimidin-3-yl][1,2,4]triazines (11a–c)
A mixture of 10a–c (0.01 mmol) and malonic acid (0.01 mmol) in AcOH
(20 ml) was refluxed for 4 h, cooled, and poured onto ice. The yielded
solid was filtered and crystallized to give 11a–c (Table II). UV (11a):
255 (2.0). IR (11a): 3364 (OH); 3080 (aromatic CH); 2923 (aliphatic
CH); 1740 (C O); 1609 (C N); 800 (phenyl group); 700 (C-Cl). 1H-NMR
(11a): 1.4, 1.6 (s, 6H, 2CH3); 7.2–8 (m, 7H, 1H, CH , 2H, CH CH,
4H, aromatic protons); 10.5 (s, 1H, OH). MS (Int.%) (11a): m/z 355.79;
342.25 (26.95); 167 (40.41); 149 (100).
3-Cyanoamino-6-methyl-5-[substituted styryl]-
[1,2,4]triazines (12a,b)
A mixture of 1b, 1d (0.01 mmol) and cyanamide (0.01 mmol) in isopropyl
alcohol (20 ml) was refluxed for 6 h, cooled, and poured onto ice. The
resultant solid was filtered and crystallized to give 12a,b (Table II). IR
(12a): 3125 (NH); 3050 (aromatic CH); 2922, 2854 (aliphatic CH); 2271
1
(CN); 1640 (CH CH); 800 (phenyl group); 720 (C-Cl). H-NMR (12a):
1.5 (s, 3H, CH3); 7.5–7.9 (m, 6H, 2H, CH CH, 4H, aromatic protons);
8.5 (s, 1H, NH-CN).
N4-(6-Methyl-5[substituted styryl][1,2,4]triazin-
3-yl)amino Guanidine (13a,b)
A mixture of 12a,b (0.01 mmol) and hydrazine hydrate (0.01 mmol)
in isopropyl alcohol (20 ml) was refluxed for 12 h, cooled, and poured
onto ice. The solid produced was filtered and crystallized to give 13a,b
(Table II). IR (13a): 3400 (NH2); 3220–3150 (NH-NH); 1700–1600 (def.
NH2, CH CH); 1520 (N CH); 780 (phenyl group); 690 (C-Cl). 1H-NMR
(13a): 1.2 (s, 3H, CH3); 2.5 (s, 2H, NH2); 7.4–8 (m, 6H, 2H, CH CH,
4H, aromatic protons); 8.5, 11 and 12.2 (each s, 3NH).

Synthesis of Heterobicyclic Nitrogen Compounds
291
3-[3-ethyl propionate Imino]-6-methyl-
5-oxo-[1,2,4]triazin-4-yl)-6-methyl-5-[substituted
Styryl][1,2,4]triazines (14a,b)
A mixture of 13a,b (0.01 mmol) and ethylbyravate (0.01 mmol) in AcOH
(20 ml) was refluxed for 4 h, cooled, and poured onto ice. The resultant
solid was filtered and crystallized to give 14a,b (Table II). IR (14b): 3100
(aromatic CH); 2917 (aliphatic CH); 1678 (C O); 1606 (C N); 1437 (def.
1
Me); 817 (phenyl group). H-NMR (14b): 0.8–1.5 (m, 15H, 5CH3); 2.2
(q, 2H, CH2); 7.4–7.7 (m, 6H, 2H, CH CH, 4H, aromatic protons). M
(Int.%): (14b): m/z 462 (52); 393 (9.36); 239 (19.42); 148.9 (100) 146
(8.65); 95 (9.36).
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