Phthalazinone in heterocyclic synthesis: Synthesis of some s-triazole, s-triazolothiadiazine, s-triazolothiadiazine, and s-triazolothiadiazole derivatives as pharmaceutical interest

Article abstract of DOI:10.1080/10426500390228666

1(2H)-Oxophthalazine-2-acetic acid ethyl ester was allowed to react with various reagents under different conditions to yield compounds 2-[(4-substituted-5-mercaptotriazol-3-yl) methyl]-1(2H)-oxophthalzines 5 and 7 which acted as starting materials for the preparation of some new s-triazolo[5,1-b][1,3]thiazine (8), s-triazolo[3,4-b][1,3,4]thiadiazine 9,12,14,20, and s-triazolo[3,4-b][1,3,4]thiadiazole 18,21 derivatives.

Full text of DOI:10.1080/10426500390228666

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Phthalazinone in Heterocyclic Synthesis: Synthesis
of Some s-Triazole, s-Triazolothiadiazine, s-
Triazolothiadiazine, and s-Triazolothiadiazole
Derivatives as Pharmaceutical Interest
a
Abu Zeid Abd El-Baset Hassanien
a
Suez Canal University, Arish, Egypt
Published online: 23 Aug 2006.
To cite this article: Abu Zeid Abd El-Baset Hassanien (2003) Phthalazinone in Heterocyclic Synthesis: Synthesis of Some
s-Triazole, s-Triazolothiadiazine, s-Triazolothiadiazine, and s-Triazolothiadiazole Derivatives as Pharmaceutical Interest,
Phosphorus, Sulfur, and Silicon and the Related Elements, 178:9, 1987-1997, DOI: 10.1080/10426500390228666
To link to this article: http://dx.doi.org/10.1080/10426500390228666
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Phosphorus, Sulfur, and Silicon, 178:1987–1997, 2003
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390228666
PHTHALAZINONE IN HETEROCYCLIC SYNTHESIS:
SYNTHESIS OF SOME s-TRIAZOLE,
s-TRIAZOLOTHIADIAZINE, s-TRIAZOLOTHIADIAZINE,
AND s-TRIAZOLOTHIADIAZOLE DERIVATIVES
AS PHARMACEUTICAL INTEREST
Abu Zeid Abd El-Baset Hassanien
Suez Canal University, Arish, Egypt
(
Received December 13, 2002; accepted April 5, 2003)
1
(2H)-Oxophthalazine-2-acetic acid ethyl ester was allowed to
react with various reagents under different conditions to yield
compounds 2-[(4-substituted-5-mercaptotriazol-3-yl) methyl]-1(2H)-
oxophthalzines 5 and 7 which acted as starting materials for
the preparation of some new s-triazolo[5,1-b][1,3]thiazine (8),
s-triazolo[3,4-b][1,3,4]thiadiazine 9,12,14,20, and s-triazolo[3,4-
b][1,3,4]thiadiazole 18,21 derivatives.
Keywords: 1(2H)Phthalazinone,2,4-dichloroanthraquinone; bromoma-
lononitrile
1
Some phthalazine derivatives exhibit potent antihypertensive,
antipyretic, and tuberculostatic3 activities. Various s-triazoles, s-
triazolo[3,4-b][1,3,4]thiadiazoles, and thiadiazines have been re-
2
4
ported to possess diveres biological activities such as antifungal,
5
6
7,8
antibacterial, antiinflammatory, and herpicidal. Also, the arylazo
group is known to be important in pormoting antinewplastic activity.9
In view of the aforesaid versatile benefits and in connection with
our previous efforts directed toward the facile synthesis of hetero-
cyclic ring systems,1
0−13
we aimed at incorporating the phthalazinone
moiety into a variety of s-triazoles, s-triazolo[3,4-b][1,3,4]thiadiazoles,
and arylazo-s-triazolo[3,4-b][1,3,4]thiadizine moieties to obtain new
The author sincerely thank Dr. Ahmed A. El-Beih, Department of Natural and
Microbial Products, National Research Center, Cairo, Egypt for antimicrobial data.
Address correspondence to Abu Zeid Abd El-Baset Hassanien, Department of
Chemistry, Faculty of Education, Suez Canal University, Arish, Egypt. E-mail: abuzeid5@
hotmail.com
1
987

1
988
A. A. Hassanien
heterocyclic compounds with expected wide spectrum of potential
applications.
The key precursor 1(2H)-oxophthalazin-2-acetic acid ethyl ester (1)
1
4
was prepared according to the reported method. Compound 1 under-
went hydrolysis with HCl and hydrazinolysis with hydrazine hydrate
and gave 1(2H)-oxophthalazine-2-acetic acid derivatives 2 and 4 respec-
1
tively. Structure 2 was confirmed on the basis of its H NMR spectrum
which revealed, in addition to the expected signals, the absence of the
ester group. Now we discribe a facile one step synthesis 2-[(4-amino-5-
mercapto-s-triazol-3-yl)methyl]-1(2H)-oxophthalazine (5) via reaction
of 2 with equimolar amounts of thiocarbohydrazide 3 under fusion con-
ditions. This method led to higher yields and shorter working times in
comparison with the reported method15 via reaction of 4 with carbon
disulfide and hydrazine hydrate.
SCHEME 1
On the other hand, reaction of 4 with KSCN (6) in refluxing ethanol
with drops of HCl gave the salt which was converted directly to 7 in
poor yield by heating in aqueous KOH followed by acidification with
HCl (Scheme 1).
Reaction of each 7 and 5 with dimethylacetylene dicarboxylate
DMAD] in refluxing methanol in the presence of a trace of acetic acid
[
gave the corresponding 1:1 adducts. Such products were formulated
as 2-[1(2H)-oxophthalizin-2-yl)methyl]-7-carbomethoxy-s-triazolo[5,1-
b][1,3]thiazine derivatives 8 and 9 respectively. Both elemental and
spectral data for 8 and 9 were consistent with the assigned structure.

Phthalazinone in Heterocyclic Synthesis
1989
Its assumed that the reaction proceeds via an addition followed by a
cyclocondensation to yield 8 and 9.
SCHEME 2
Similarly, compound 5 reacted with a variety of methyl N-aryl-
2
-oxopropanehydrazonyl chloride10 (10a–c) in ethanol in the pres-
ence of NaOC2H5 to afford the respective 7-arylhydrazono-3 [(1(2H)-
oxophthalazin-2-yl)methyl]-s-triazolo[3,4-b][1,3,4]thiadiazine 12 via
an in situ dehydrative-cyclization of the initially formed thiohydra-
zonate 11a–c under the reaction conditions (Scheme 2). The structures
of 12a–c were established on the basis of their elemental analysis and
1
1
spectral data (MS, H NMR, IR). Thus, the H NMR of 12a–c revealed in
each case the presence of only one NH proton signal at δ 10.54, besides
the expected signals. The molecular ion peak of 12a [m/z = 416 (100%)]
corresponded to the molecular formula C20H16N8OS. The intermedi-
ate 5 condensed with alkyl halides such as 4-chloroacetyl antipyrine,10
phenacylbromide, and chloroacetone 13a–c, respectively, in refluxing
ethanol in the presence of triethylamine as a catalyst to yield the cor-
responding s-triazolo[3,4-b][1,3,4]thiadiazines 14a–c respectively. The
analytical and spectral data of 14a–c were in accordance with the pro-
1
posed structures. The IR and H NMR spectra of the dicycles show the
absence of signals due to NH2 or NH group, and the presence of signals
in the region of δ 4.13–4.30 were attributed to the protons adjacent
to sulfur atom, in addition to the expected signals. Coupling attempts
of 14c with aryldiazonium chlorides to obtain 12 were unsuccessful
(
Scheme 3).
The intermediate 5 reacted with arylisothiocyanates1
4−18
16a in re-
fluxing ethanol and 16b in dry acetone to produce 18a,b, respectively,
via the nonisolable intermediate 17 by loss of one mole of H2S. The
proposed structure was in agreement with the analytical and spectral
data (Scheme 4).
In addition, reaction of 5 with 2,3-dichloronaphthoquinone ef-
fected a cyclization to furnish the corresponding s-triazolo[3,4-b][1,3,

1
990
A. A. Hassanien
SCHEME 3
4
]-thiadiazine derivative 19 via elimination of two mmol of HCl. Its
IR spectrum showed bands at 3290 (NH), 1685 and 1668 (2 C O). The
mass spectrum of 19 revealed a molecular ion peak m/z 428 (M , 100%).
+
Furthermore, the triazolo[3,4-b][1,3,4]thiadiazine derivative 20 also
was prepared by reaction of 5 with bromomalononitrile. Both elemental
analysis and spectral data are consistent with the assigned structure.
Thus, the IR spectrum showed bands at 3320, 3200 (NH, NH2), and
−1
+
2
192 cm (C N). The mass spectrum revealed m/z 338 (M , 100%)
corresponding to the molecular formula C14H10N8OS .
Finally, the dicyanotriazolothiadiazole derivative 21 was obtained by
reaction of 5 with ketene dithioacetale.11 The IR spectrum of 20 showed
−
1
−1
1
bands at 3380 (NH), 3219 (C N), and 1668 cm (C O) cm . Its H-
NMR spectrum exhibited a singlet at δ 12.9 (NH) besides the expected
signals.
Antimicrobial Activity
Preliminary biological activity screening of some synthesized com-
pounds has been performed against microorganisms representing
gram-positive bacteria (Bacillus subtills), gram-negative bacteria (E.
coli), yeast (Candida albican), and fungi (Aspergillus niger), using the

Phthalazinone in Heterocyclic Synthesis
1991
SCHEME 4
bioassay technique of antibiotics19 specified in U.S. pharmacopoeia.
Ampicillin and chloramphenicol were used as standards. The results
obtained are summarized in Table I.
EXPERIMENTALS
Melting points are uncorrected. IR spectra were recorded with a FTIR-
1
8
201 PC spectrophotometer Shimadzu. H-NMR spectra were obtained
TABLE I Antimicrobial Activity of Some Newly
Synthesized Compounds
Candida
albican
Asp.
niger
Comp. no.
B. subtillis
E. coli
7
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
−
−
−
−
+
+
+
+
1
1
1
2c
4a
9
Ampicillin
Chloramphenicol

1
992
A. A. Hassanien
on a Varian Germini 200 MHz spectrometer in DMSO-d6 as solvent
and TMS as an internal reference. Mass spectra were performed on a
Shimadzu GCMS-QP-1000 EX using the direct inlet system and EI + QI
MSLMRUPLR. Microanalysis were performed by the Microanalytical
Unit at Cairo University. Thin layer chromatography was carried out
on 5 × 20 cm sheets coated with silica gel GF 254 type 60, mesh size
50–250.
1
(2H)-Oxophthalazine-2-acetic Acid (2)
A mixture of 1 (0.2 mmol) and HCl (200 ml, 5%) was refluxed for 2 h,
and the solid obtained after cooling was filtered and recrystallized from
◦
acetic acid to yield pale yellow crystals, yield 80%, m.p. 248 C. IR: 3450
(
−
1 1
OH), 1700 (C O), 1658 (C O) cm . HNMR (DMSO-d6) δ 4.93 (s, 2H,
CH2), 7.41–7.93 (m, 5H, H Ar + H4-phthalazine), 11.63 (br, 1H, OH)
ppm.
MS: m/z 204 (M+, 45%). Anal. calcd. for C10H8N2O3: C, 58.82; H,
3
.92; N, 13.72; Found: C, 58.90; H, 3.80; N, 13.90.
1
(2H)-Oxophthalazine-2-acetic Acid Hydrazide (4)
To a solution of 1-phthalazone-2-acetic acid ethyl ester (1), (0.01 mmol)
in ethanol (30 ml) was added hydrazine hydrate (0.05 mmol). The re-
action mixture was heated under reflux for 1 h. The precipitate ob-
tained was filtered, dried, and recrystallized from DMF, to yield color-
◦
less crystals, m.p. 185 C; IR: 3300 (NH2), 3160 (NH), 1685 (C O), 16510
(
−1
+
C O) cm ; MS: m/z = 218 (M , 82%), Anal. Calcd. for C10H10N4O2:
C, 55.04; H, 4.58; N, 25.68. Found: C, 55.10; H, 4.60; N, 26.10.
2
[(4-Amino-5-mercapto-s-triazol-3-yl)]methyl]-1(2H)-
phthalazinone (5)
Method 1: The method of Reid and Heindel15 was followed. The solid
◦
obtained was crystallized from ethanol, m.p. 243 C. IR: 3301 (NH2),
2
−
1
1
931 (CH2), 2769 (SH), 1656 (CO) cm ; H NMR (DMSO-d6) δ 5.10
(
(
s, 2H, CH2), 6.1 (s, 2H, NH2), 7.2–7.91 (m, 5H, H Ar + H4-phth) 13.46
+
s, 1H, SH)ppm; MS: m/z 274 (62.4%, M ), 132 (100), 89 (33). Anal.
Calcd. for C11H10N6OS: C, 48.17; H, 3.64; N, 30.65; S, 11.67. Found: C,
4
8.00; H, 3.60; N, 30.80; S, 11.60.
Method 2: A mixture of thiocarbohydrazide 3 (0.01 mmol) and 2
◦
(
0.01 mmol) was fused at 190–200 C in an oil bath for 15 min. After
cooling, the reaction mixture was triturated with ethanol, and the solid

Phthalazinone in Heterocyclic Synthesis
1993
obtained was crystallized from ethanol to give a single product which
was found to be identical in all aspects (m.p., mixed m.p. and IR data)
with a product from Method 1.
2
-[(5-Mercapto-s-triazol-3-yl)methyl]-1(2H)-
phthalazinone (7)
A mixture of 4 (0.01 mmol) and KSCN 6 (0.05 mmol) was refluxed in
20 ml EtOH containing few drops of conc. HCl for 3 h. The precipitate
formed was collected by filtration and dried to give the salt which was
used without further purification. A mixture of the salt (0.01 mmol) and
KOH (0.013 mmol) was refluxed in 25 ml of H2O for 3 h. The reaction
mixture was cooled and then acidified with HCl. The solid formed was
collected and recrystallized from ethanol to give 7 (35%) as a white
◦
−1
1
crystals, m.p. 280 C; IR (KBr): 3200 (NH), 1668 (CO) cm ; H NMR
DMSO-d6): δ 5.89 (s, 2H, CH2), 7.84–7.97 (m, 5H, Ar H + H4-phth.),
3.3 (s, 1H, NH), 13.91 (s, 1H, SH) ppm. Anal. Calcd. for C11H9N5OS:
C, 50.96; H, 3.47; N, 27.02. Found: C, 50.80; H, 3.60; N, 27.10.
(
1
2
-[(1(2H)-Oxophthalazin-2-yl)methyl]-7-carbomethoxy-s-
triazolo[5,1-b][1,3]thiazine-5-one (8)
To 7 (0.005 mmol) and DMAD (0.008 mmol) dissolved in methanol
(
30 ml) was added, a trace glacial acetic acid, and the mixture refluxed
for 6 h. Upon cooling, a product separated out, was collected and re-
crystallized from methanol to give a white crystals, m.p. 193 C. IR:
1
◦
−
1 1
730 (C O, ester), 1705 (C O), 1663 (C O) cm ; H NMR (DMSO-d6)
δ: 3.72 (s, 3H, CH3), 5.46 (s, 2H, CH2), 7.1–8.01 (m, 6H, H Ar + H4-
+
phtha. + H-5-thiazole) ppm; MS: m/z = 369 (M , 80%). Anal. Calcd. for
C16H11N5O4S: C, 52.03; H, 2.98; N, 18.97; S, 8.67. Found: C, 52.20; H,
3.10; N, 19.20; S 8.80.
2
-[(1(2H)-Oxophthalazin-2-yl)methyl]-7-
carbomethoxymethylene-s-triazolo[3,4-b][1,3]-
thiadiazine-6-one (9)
This compound similarly prepared as mentioned in the previous exper-
iment from 5 (0.005 mmol) and DMAD (0.008 mmol) and was isolated
◦
as white crystals, m.p. 265 C. IR: 3350 (OH), 1725 (C O, ester), 1700
(
−1 1
C O), 1662 (C O) cm ; H NMR (DMSO-d6) δ: 3.81 (s, 3H, CH3), 5.63
(
s, 2H, CH2), 7.10 (s, 1H, olefinic proton), 7.34–8.1 (m, 5H, H Ar + H4-
+
phtha.), 10.64 (s, 1H, NH) ppm; MS: m/z = 384 (M , 63%), Anal. Calcd.

1
994
A. A. Hassanien
for C16H12N6O4S: C, 50.00; H, 3.13; N, 21.87; S 8.33. Found: C, 50.10;
H, 3.20; N, 22.10; S 8.60.
N-aryl-2-oxo-propanehydrazonyl Chlorides 10a---c were
Prepared Accordance to Hassanien10
7
-Arylhydrazono-3-[(1(2H)-oxophthalazin-2-yl)methyl]-6-
methyl-5H-s-triazolo-[3,4-b][1,3,4]thiadiazines (12a---c)
General Procedure. To a mixture of equimolar quantities of the ap-
propriate hydrazonyl chloride 10 and compound 5 (0.01 mmol) in abso-
lute ethanol (30 ml) was added gradually triethyl amine (0.01 mmol).
The reaction mixture was refluxed for 3–4 h. After cooling the solid
product was filtered and recrystallized from EtOH.
7
-Phenylhydrazino-3-[(1(2H)-oxophthalazin-2-yl)methyl]-
-methyl-5H-s-triazolo-[3,4-b][1,3,4]thiadiazines (12a)
6
M.p. 296.8 C. IR: 3178 (NH), 2954 (CH-aliph.), 1651 (CO) cm−1; 1H
◦
NMR (DMSO-d6) δ 1.2 (s, 3H, CH3), 5.98 (s, 2H, CH2), 7.10–7.89 (m,
1
0H, H Ar + H4-phthala.), 10.5 (s, 1H, NH) ppm; MS: m/z 416 (100%,
+
M ), 283 (14%), 171 (25%), 132 (43.7%). Anal. Calcd. for C20H16N8OS:
C, 57.69; H, 3.84; N, 26.92; S, 7.69. Found: C, 57.50; H, 3.80; N, 27.10;
S, 8.00.
7
-(p-Tolyl)hydrazino-3-[(1(2H)-oxophthalazin-2-yl)-
methyl]-6-methyl-5H-s-triazolo[3,4-b]-
[
1,3,4]thiadiazines (12b)
◦
−1
1
M.p. 305 C. IR: 3209 (NH), 2981 (CH-aliph.), 1655 (CO) cm ; H
NMR (DMSO-d6) δ 1.27 (s, 3H, CH3), 2.31 (s, 3H, CH3), 5.81 (s, 2H,
CH2), 7.01–7.84 (m, 9H, H Ar + H4-phthal.), 10.61 (s, 1H, NH) ppm.
Anal. Calcd. for C21H18N8OS: C, 58.60; H, 4.18; N, 26.04; S, 7.44. Found:
C, 58.30; H, 4.30; N, 25.80; S, 7.60.
7
-(p-Sulphonamidophenyl)hydrazino-3-[(1(2H)-
oxophthalazin-2-yl)methyl]-6-methyl-5H-s-triazolo[3,4-b]-
1,3,4]thiadiazines (12c)
[
M.p. 290 C. IR: 3302 (SO2NH2), 3180 (NH), 1656 (CO) cm−1; 1H NMR
DMSO-d6) δ 1.34 (s, 3H, CH3), 5.91 (s, 2H, CH2), 7.01–7.98 (m, 11H,
H Ar + SO2NH2 + H-4-phthala.), 10.63 (s, 1H, NH) ppm; MS: m/z
495, 100%), 418 (26%), 289 (30%). Anal. Calcd. for C20H17N9O3S2: C,
◦
(
(
4
1
8.48; H, 3.43; N, 25.45; S, 12.92. Found: C, 48.70; H, 3.60; N, 25.10; S,
3.20.

Phthalazinone in Heterocyclic Synthesis
1995
3
-[(1(2H)-Oxophthalazin-2-yl)Methyl]-6-substituted-7H-
s-triazolo[3,4-b][1,3,4]thiadiazines (14a---c)
A mixture of 5 (0.01 mmol), proper α-haloketones 13a–c (0.01 mmol),
and fused potassium carbonate (0.04 mmol) in absolute ethanol (80 ml)
was refluxed for 8–10 h. After the removal of EtOH under reduced
presseure, the resulting solid was washed with water, filtered, and re-
crystallized from EtOH.
3
-[(1(2H)-Oxophthalazin-2-yl)Methyl]-6-phenyl-7H-s-
triazolo[3,4-b][1,3,4]thiadiazines (14a)
M.p. 258 C. IR: 2981 (CH-aliph.), 1666 (C O) 726 (C S C) cm−1; 1H
◦
NMR (DMSO-d6) δ 4.39 (s, 2H, CH2), 5.81 (s, 2H, CH2), 7.41–8.48 (m,
+
1
0H, Ar H) ppm; MS: m/z 374 (100%, M ), 272 (24%), 216 (13%), 132
(
2
77%), 77 (99.1%). Anal. Calcd. for C19H14N6OS: C, 60.96; H, 3.74; N,
2.45; S, 8.55. Found: C, 61.30; H, 3.80; N, 22.50; S, 9.10.
3
-[(1(2H)-Oxophthalazin-2-yl)Methyl]-6-(antipyrin-4yl)-
H-s-triazolo[3,4-b][1,3,4]thiadiazines (14b)
7
M.p. 315 C. IR: 2988 (CH-aliph.), 1665, 1657 (2CO) cm−1; 1H NMR
◦
(
(
DMSO-d6) δ 1.36 (s, 3H, CH3), 2.45 (s, 3H, CH3), 4.13 (s, 2H, CH2), 5.95
s, 2H2, CH2) 7.61–8.10 (m, 10H, H Ar + H4-phth.) ppm. Anal. Calcd.
for C24H20N8O2S: C, 59.50; H, 4.13; N, 23.14; S, 6.61. Found: C, 59.60;
H, 4.30; N, 23.30; S, 6.70.
3
-[(1(2H)-Oxophthalazin-2-yl)Methyl]-6-methyl-7H-s-
triazolo[3,4-b][1,3,4]thiadiazines (14c)
M.p. 229 C. IR: 2980, 2895 (CH-aliph.), 1658, (C O) cm−1; 1H-NMR
◦
(
7
DMSO-d6) δ 1.12 (s, 3H, CH3), 4.31 (s, 2H, CH2), 5.64 (s, 2H, CH2),
.1–7.93 (m, 5H, H Ar + H4-phth.). MS: m/z 312 (100%). Anal. Calcd.
for C14H12N6OS: C, 53.84; H, 3.84; N, 26.92; S, 10.25. Found: C, 54.10;
H, 4.00; N, 27.10; S, 9.90.
6
-Phenylamino-3-[(1(2H)-oxophthalazin-2-yl)methyl]-s-
triazolo[3,4-b][1,3,4]thiadiazole (18a)
A mixture of 5 (0.01 mmol), arylisothiocyanates 16 (0.01 mmol) and
absolute ethanol (30 ml) was refluxed for 7 h. The solid so formed was
◦
collected and crystallized from ethanol. m.p. 180 C. IR: 3425 (NH), 3047
(
7
−1
1
H Ar), 1660 (C O) cm . H NMR (DMSO-d6) δ 5.86 (s, 2H, CH2),
.61–7.98 (m, 10H, H Ar + H4-phtha), 10.61 (s, 1H, NH) ppm; MS
m/z: 375 (100%), 245 (89%), 118 (43%), 77 (49.7%). Anal. Calcd. for

1
996
A. A. Hassanien
C18H13N7OS: C, 57.60; H, 3.46; N, 26.13; S, 8.53. Found: C, 57.90; H,
.40; N, 26.30; S, 8.80.
3
6
-Benzoylamino-3-[(1(2H)-oxophthalazin-2-yl)methyl]-s-
triazolo[3,4-b][1,3,4]thiadiazole (18b)
To a solution of benzoylisothiocyanate [prepared from (1.5 ml,
0
.01 mmol) benzoyl chloride, and (0.98 g, 0.01 mmol) potassium thio-
cyanate in dry acetone in situ] was added (0.01 mmol) of compound 5,
after boiling for 2 h, the reaction mixture was cooled, the solid was sep-
arated, and crystallized from ethanol to give pale yellow crystals, m.p.
◦
−1
1
193–5 C. IR: 3278 (NH), 1695, 1670 (2C O) cm ; H NMR (DMSO-d6)
δ 5.69 (s, 2H, CH2), 7.01–7.89 (m, 10H, H Ar + H4-phtha), 12.5 (s, 1H,
NH) ppm; MS: m/z 403 (100%), 217 (24%), 77 (43%). Anal. Calcd. for
C19H13N7O2S: C, 56.57; H, 3.22; N, 24.31; S, 7.94. Found: C, 56.80; H,
3.10; N, 24.30; S, 8.10.
3
-[(1(2H)-Oxophthalazin-2-yl)methyl]-6,11-dioxo-5H-
naphtho[2,3-e]-s-triazolo[3,4-b][1,3,4]thiadiazine (19)
A
mixture of (0.01 mmol) and 2,3-dichloronaphthoquinone
5
(
0.01 mmol) in dimethylformamide (20 ml) containing (0.01 mmol) of
triethylamine was refluxed for 18 h. The precipitate formed was col-
◦
lected by filtration and recrystallized from ethanol, m.p. > 300 C. IR:
3
−
1 1
290 (NH), 1685, 1668 (C O) cm . H NMR (DMSO-d6) δ 5.93 (s, 2H,
CH2), 7.01–8.1 (m, 9H, H Ar + H4-phtha), 12.31 (s, 1H, NH) ppm; MS:
m/z 428 (100%), 304 (24%), 246 (18%). Anal. Calcd. for C21H12N6O3S:
C, 58.87; H, 2.80; N, 19.62; S, 7.47. Found: C, 58.90; H, 2.90; N, 19.90;
S, 7.60.
3
-[(1(2H)-Oxophthalazin-2-yl)methyl]-6-amino-5H-s-
triazolo[3‘,4‘-b][1,3,4]thiadiazine-7-carbonitrile (20)
A mixture of 5 (0.01 mmol), bromomalononitrile (0.01 mmol), and potas-
sium hydroxide (0.01 mmol) in ethanol (30 ml) was refluxed for 2 h.
The solid obtained was collected by filtration and recrystallized from
◦
−1
ethanol, m.p. 282 C. IR: 3320, 3290 (NH2, NH), 2192 (C N) cm
;
1
H NMR (DMSO-d6) δ 5.81 (s, 2H, CH2), 6.98 (br, 2H, NH2), 7.41–
7
.89 (m, 5H, H Ar + H4-phtha), 12.84 (s, 1H, NH) ppm; MS: m/z 338
+
(
M , 100%), 248 (13%), 175 (33%), Anal. Calcd. for C14H10N8OS: C,
4
9
9.70; H, 2.95; N, 33.13; S, 9.46. Found: C, 49.60; H, 3.10; N, 33.20; S,
.60.

Phthalazinone in Heterocyclic Synthesis
1997
6
-Dicyanoethylidine-3-[1(2H)-oxophthalazin-2-yl)-
methyl]-5H-s-triazolo[3,4-b][1,3,4]thiadiazole (21)
A mixture of 5 (0.01 mmol), ketene dithioacetale (0.01 mmol), and tri-
ethylamine (0.01 mmol) in dimethylformamide (20 ml) was refluxed for
1
5 h. The obtained solid was collected by filtration and recrystallized
◦
−1
from ethanol, m.p. 292 C. IR: 3380 (NH), 2219 (C N), 1668 (C O) cm
;
1
H NMR (DMSO-d6) δ 5.78 (s, 2H, CH2), 7.1–7.89 (m, 5H, H Ar + H4-
phtha), 12.9 (s, 1H, NH) ppm; Anal. Calcd. for C15H8N8OS: C, 51.72; H,
2.29; N, 32.18; S, 9.19. Found: C, 51.90; H, 2.30; N, 32.20; S, 9.30.
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