Studies on the reaction of α-chloroformylarylhydrazine hydrochloride1 with N-heterocyclic compounds

Article abstract of DOI:10.1002/jccs.200200037

In addition to pyridines, α-chloroformylarylhydrazine hydrochloride 1 can also react with some N-heterocyclic compounds. The cycloaddition of 1 with isoquinoline was achieved to obtain 3. The production of 4, 5, 6 given by cycloaddition of 1 with pyridazine was dependent on the reaction condition. Some heterocyclic compounds bearing an X-C=N (X:S, N) group on the ring can react with 1 to gain the derivatives of 2,4-dihydro-1,2,4-triazol-3-one. 7, 8, 9 and 10 were given by reaction of 1 with 1,3,5-triazine, 1,4,5,6- tetrahydropyrimidine, 1,3-thiazole and 2-amino-1,3-thiazole, respectively. The reactions for 2-amino-1,3,4-thiadiazole and 3-amino-1,2,4-triazole had the same product 11.

Full text of DOI:10.1002/jccs.200200037

JournaloftheChineseChemicalSociety, 2002, 49, 239-249
239
Studies on the Reaction of a -Chloroformylarylhydrazine Hydrochloride1
with N-heterocyclic Compounds
Chun-Yen Chiua,b
Wen-Fa Kuoa (
(
), Chao-Nan Kuoa (
),
)
) and Mou-Yung Yeha* (
aDepartmentofChemistry,NationalChengKungUniversity,Tainan,Taiwan70101,R.O.C.
bDepartmentofEnvironmentalEngineeringandHealth,TajenInstituteofTechnology,
Pingtung, Tai wan 907, R.O.C.
In ad di tion to py ri dines,a -chloroformylarylhydrazinehydrochloride 1 can also re act with some N-
heterocyclic com pounds. The cycloaddition of 1 with isoquinoline was achieved to ob tain 3.Theproduction
of 4, 5, 6 given by cycloaddition of 1 with pyridazine was de pend ent on the re ac tion con di tion. Some
heterocyclic com pounds bear ing an X-C=N (X:S, N) group on the ring can re act with1togainthederivatives
of 2,4-dihydro-1,2,4-triazol-3-one. 7, 8, 9 and 10 were given by re ac tion of 1 with 1,3,5-triazine, 1,4,5,6-
tetrahydropyrimidine, 1,3-thiazole and 2-amino-1,3-thiazole, re spec tively. The re ac tions for 2-amino-1,3,4-
thiadiazole and 3-amino-1,2,4-triazole had the same prod uct11.
INTRODUCTION
RESULTS AND DISCUSSION
a -Chloroformylarylhydrazinehydrochloride1 1 devel-
oped by our lab was an ac tive com pound pos sess ing both
amino and chloroformyl groups. Many heterocyclic com-
poundsexhibitingbiologicalandpharmacologicalactivities
could be syn the sized through1. In our past re search,2 1 re-
acted with py ri dines to give 2-aryl-2H-[1,2,4]triazolo[4,3-
a]pyridin-3-ones 2 (Scheme I). It was re ported that hetero-
cyclic com pounds bear ing 2,4-dihydro-1,2,4-triazol-3-one
exhibitedvariousmedicalproperties.3,4,6 Most of these com-
poundsareappliedasinsecticides.5 Since the cycloadditon
reactionof1 withpyridineswasdonewithagoodyieldunder
mild con di tions, we thought the re ac tion for some other ar o-
matic com pounds bear ing the C=N group could also take
place in such a re ac tion sys tem. Fo cusing on this as pect, it
was very in ter est ing to study the re ac tion of 1 with many
otherN-heterocycliccompounds. Inthispaper, weproceeded
with the cycloaddition of 1 with many N-heterocyclic com-
pounds in clud ing six-member and five-member rings.
Reactionof a -chloroformylarylhydrazine hy dro chlo-
ride 1 with:
A. isoquinoline
Com pound1 re acted with isoquinoline at 80 °C un der
an open sys tem and when the re ac tion was com pleted, we
foundonlyonemajorcompoundwasobtained. Thestructure
of this prod uct was as cer tained as 2-aryl-2H-[1,2,4]triazolo-
[3,4-a]isoquinolin-3-one 3 shown in Fig. 1 by X-ray spec-
trumanalysis.Accordingtothisresult,wefoundthereaction
was a cycloaddition re ac tion which was sim i lar to that of 1
Scheme I
H
O
C
H
N
N
O
N
N
Ar
N
Cl
Ar
N
Ar
N
.
NH2 HCl
N
Fig. 1. Molecular structure of 2-(p-chlorophenyl)-
2 H-[1,2,4]triazolo[4,3-b]isoquinolin-3-one 3c.
O
1
2

240 J. Chin. Chem. Soc., Vol. 49, No. 2, 2002
Chiu et al.
Scheme II
O
N
O
N
O
N
Ar
N
C
Cl
N
N
N
Ar
NH2
H
Ar
.
NH2 HCl
Cl
H
1
O
N
-2H
N
N
Ar
3
with pyridine and the cycloaddition re ac tion site was at the
num ber 1 car bon of isoquinoline, but not at the num ber 3 car-
bon (Scheme II). This re ac tion se lec tiv ity for isoquinoline
agreed with those re ported in most other re ac tions. The yield
ofthisreactionisdemonstratedinTable1.
fore, when low er ing the con cen tra tion of pyridazine in re ac-
tant mix tures, it was ad van ta geous for1 to pro ceed to two
times cycloaddition with one pyridazine mol e cule to ob tain
5. Be cause 4c was dif fi cult to dis solve in re ac tion sol vent
iPrOH, cycloaddition re ac tion of 1c with pyridazine was
stopped on 4c un der the first con di tion. 4 ob tained from one
B. Pyridazine
The prod ucts of cycloaddition re ac tion of 1with pyr id-
azineweredependentonreactionconditions.Underthefirst
condition:25°C, low ra tio of pyridazine (pyridazine/1 = 1:1),
addingtributylamineandusingiPrOHasreactionsolvent, 1a
and 1b could be con verted to 2,7-diaryl-2,3,3a,5a,6,7-hex-
ahydro-[1,2,4]triazolo[4,3-a]pyridin-3-ones 5; but un der the
sameconditions,2-(p-chlorophenyl)-2,8a-dihydro-1H-[1,2,4]-
triazolo[4,3-b]pyridazin-3-one 4c was pro duced from 1c.
The struc tures of 4c and 5a were con firmed by X-ray spec-
trumanalysis( Fig. 2, Fig. 3).Underthesecondcondition:the
same as the first con di tion but with a high ra tio of pyridazine
(pyridazine/1 = 5:1) and in ab sence of tributylamine, only 4c
was iso lated. Un der the third con di tion: the same as the sec-
ond con di tion but at higher tem per a ture (60 °C), 2-aryl-2H-
[1,2,4]triazolo[4,3-b]pyridazin-3-one 6 was given by 1a, 1b
and 1c. The yield of all re ac tions is shown in Table2. The
abovereactionroutesdemonstratedinScheme III could sug-
gest that 1 re acted with pyridazine to pro duce 4 at first and
then 4 un der went cycloaddition re ac tion with the sec ond
molecule1 to ob tain5 or dehydrogenation to gain 6. There-
Table 1. Reaction of 1 with Isoquinoline
Product
Ar
Yield/ %
3a
3b
3c
C6H5
p-CH3C6H4
p-ClC6H4
76
82
81
Fig. 2. Molecularstructureof2-(p-chlorophenyl)-2,8a-
dihydro-1H-[1,2,4]triazolo[4,3-b]pyridazin-3-
one 4c.

Reactionofa -Chloroformylarylhydrazine
J. Chin. Chem. Soc., Vol. 49, No. 2, 2002 241
Scheme III
H
N
H
N
O
N
Ar
N
O
N
Ar
N
O
Ar
N
C
Cl
N
N
N
.
N
NH
2 HCl
4
6
1
1
H
H
H
H
N
N
N
N
N
N
Ar
Ar
O
O
5
Table 2. Reaction of 1 with Pyridazine
Product
Ar
25 °C, 1/
25 °C, 1/
60 °C, 1/
pyridazine = 1:1
pyridazine = 1:5
pyridazine = 1:5
Yield/%
Yield/%
Yield/%
4c
5a
5b
6a
6b
6c
p-ClC6H4
C6H5
p-CH3C6H4
C6H5
p-CH3C6H4
p-ClC6H4
80
57
24
-----
-----
-----
85
-----
-----
-----
64
72
78
-----
-----
-----
-----
-----
cycloadditionreactionwasfavoredbyenhancingtheconcen-
tra tion of pyridazine in re ac tant mix tures; but 4a and 4b
couldnotbeisolatedeasily, becausetheirsolubilityinwater
was too good to be sep a rated from pyridazine. When en hanc-
ing the tem per a ture and the con cen tra tion of pyridazine,6
was pro duced through one cycloaddition and then de hy dro-
genationfromintermediate4. This syn thetic route could be-
come true by con vert ing 4c to 6c atahighertemperature(60
°C) and the yield ob tained was ninety two percents.
C. 1,3,5-triazine
Using isopropyl alcohol as reaction solvent, 1 was
stirred with 1,3,5-triazine at room tem per a ture. When the re-
ac tion was com pleted, the re ac tion mix ture was poured into
ice wa ter and the pre cip i tate ob tained was an a lyzed by el e-
mentalanalysis,1H NMR and MASS spec trum anal y sis. We
found this com pound could be as cer tained as 2-aryl-2,4-
dihydro-1,2,4-triazol-3-one 7 by com par ing it with the spec-
trum of the same com pound which had been re ported.7-8 This
re sult was not ex pected for us be cause of the dif fer ence from
theabovetworeactions. ThereactionrouteshowninS cheme
IV, we thought, was that the cycloaddition of 1 with 1,3,5-
triazine was done first and then the 1,3,5-triazine ring of
cycloadduct was bro ken into 7.
D. 1,4,5,6-tetrahydropyrimidine
Fig. 3. Molecular structure of 2,7-diphenyl-
2,3,3a,5a,6,7-hexahydro-2,3,6,7,8a,8b-hexaaz
a-as-indacene-1,8-dione 5a.
When the above sug gested re ac tion route was in ves ti-
gated, it was an interesting guess that the reactions for

242 J. Chin. Chem. Soc., Vol. 49, No. 2, 2002
Chiu et al.
Scheme IV
N
H
N
H
N
N
N
N
N
H
Ar
N
Ar
N
N
N
H
O
O
O
C
7
Ar
N
Cl
.
NH2
HC l
1
N
H
N
H
H
H
N
N
N
N
Ar
N
N
Ar
N
(C H2)3NH2
O
O
1
H
N
Ar
N
O
C
N
(CH2)3NH
N
Ar
O
NH2
8
N
N
No reaction
N-heterocycliccompoundspossessinganN-C=Ngroupwere
in volved in the ring-opening of a cycloadduct in ter me di ate.
Therefore, 1,4,5,6-tetrahydropyrimidine which possesses
one N-C=N group was tested to re act with 1 at 60 °C in the
pres ence of tributylamine. The ma jor prod uct was iso lated
and con firmed as 4-[3-(2-aryl-2,4-dihydro-1,2,4-triazol-3-
on-4-yl)propyl]-2-arylsemicarbazide 8. Ac cord ing to the
struc ture of8, the re ac tion route could be guessed as shown in
Scheme IV and, we found, was also in volved in the ring-
openingofthecycloadductintermediate.Foranothertestfor
pyrimidine,theanticipatedresultwasnotfound.Thereason,
we thought, might be that the ba sic ity of py rim i dine was too
weak for this re ac tion sys tem to pro ceed to cycloaddition
with 1.
Theresultsoftheabovereactionscreated moreinterest
in the re ac tion of 1 with other heterocyclic com pounds pos-
sess ing an X-C=N (X:S, N) group on the ring. In this study,
we searched for some five-member heterocyclic com pounds
bear ing X-C=N (X:S, N) group to un dergo re ac tion with 1.
E. 1,3-thiazole
isopropyl al co hol at 0 °C for 30 min utes. The mix ture was
poured into ice wa ter and the pre cip i tate recrystalized from
THF + isopropyl al co hol was iden ti fied as (1-arylhydrazino)
carboxylic acid (2-(2-aryl-2,4-dihydro-1,2,4-triazol- 3-on-
4-yl)vinyl)thiolate 9 by elementalanalysis, 1H NMR and
MASSspectrumanalysis. Theproposedreactionroutedem-
on strated in Scheme V re sem bled that for 1,4,5,6-tetra hy-
dropyrimidine. As a sul fur atom has better nucleophility, the
secondintermediateinwhichthecycloadductintermediate
wasbrokenintoalsounderwentnucleophilicreactionwith1.
F. 2-amino-1,3-thiazole
Followingtheabovereactionstepsbutatroomtemper-
a ture, we could ob tain (1-arylhydrazino) carboxylic acid (2-
(2-aryl-4-amino-2,4-dihydro-1,2,4-triazol-3-on-4-yl)vinyl)-
thiolate 10. This re sult was sur pris ing be cause the amino
group of 2-amino-1,3-thiazole was re tained over the re ac tion.
The rea son why the re ac tion took place in the C=N not the
NH2 group, we thought, was that the ni tro gen atom of the
C=Ngroupwhichacceptedtheresonanceeffectoftheamino
group was more ba sic than that of the amino group.
1 was stirred with 1,3-thiazole at a ratio of 1/3 in
G. 2-amino-1,3,4-thiadiazole

Reactionofa -Chloroformylarylhydrazine
J. Chin. Chem. Soc., Vol. 49, No. 2, 2002 243
Scheme V
N
H
N
R
N
R
N
R
S
SH
Ar
N
S
Ar
N
N
O
O
1
R
N
O
C
Ar
N
O
N
S
N
Ar
Ar
N
C
Cl
NH
Ar
N
2
O
.
NH HCl
2
R: H
NH
9
1
10
2
H
N
N
NH
NH
N
2
2
X
N
N
NH
2
N
XH
X
N
Ar
N
N
N
O
X: S , NH
O
1
O
O
N H
2
NH
2
N
Ar
Ar
N
N
N
N
N
N
N
N
Ar
Ar
N
N
O
O
H
HX
H
11
2-Amino-1,3,4-thiadiazolewhosestructurewassimilar
to 2-amino-1,3-thiazole was tested to re act with1 by the same
reactionsteps.Theisolatedproductwasverifiedas5-amino-
bis(2-aryl-2,4-dihydro-1,2,4-triazol-3-on-4-yl) 11 by el e-
mentalanalysis,1HNMRandMASSspectrumanalysis.This
re sult was dif fer ent from that for 2-amino-1,3-thiazole. As
the pro posed syn thetic route (Scheme V) in di cated, the sec-
ond in ter me di ate un der went cycloaddition but not nucleo-
philicsubstitutionwiththesecondmolecule1.
Table 3. Reaction of 1 with 1,3,5-Triazine (A); 1,4,5,6-
Tetrahydropyrimidine (B); 1,3-Thiazole (C); 2-Amino-
1,3-thiazole (D); 2-Amino-1,3,4-thiadiazole (E); 3-
Amino-1,2,4-triazole (F)
Product
Ar
Reagent
Yield/%
7a
7b
7c
8a
8b
8c
9a
9b
10a
10b
11a
11b
11c
11a
11b
11c
C6H5
p-CH3C6H4
p-ClC6H4
C6H5
p-CH3C6H4
p-ClC6H4
C6H5
p-ClC6H4
p-CH3C6H4
p-ClC6H4
C6H5
p-CH3C6H4
p-ClC6H4
C6H5
A
A
A
B
B
B
C
C
D
D
E
E
E
F
87
84
88
72
78
77
88
92
85
91
78
84
73
67
65
54
H. 3-amino-1,2,4-triazole
3-Amino-1,2,4-triazole,anothercompoundresembling
2-amino-1,3,4-thiadiazole in struc ture, was cho sen to re act
with 1. The ob tained prod uct was the same as 11.According
to this re sult, we thought this re ac tion fol lowed the same re-
ac tion route as that for 2-amino-1,3,4-thiadiazole (Scheme
V). The yields of the re ac tions for 1,3,5-triazine, 1,4,5,6-
tetra hydropyrimidine, 1,3-thiazole, 2-amino-1,3-thiazole,
2-amino-1,3,4-thiadiazole and 3-amino-1,2,4-triazole are
demonstratedinTable3.
p-CH3C6H4
p-ClC6H4
F
F

244 J. Chin. Chem. Soc., Vol. 49, No. 2, 2002
Chiu et al.
CONCLUSION
(3a): col or less nee dles; mp 139-139.5 °C; IR (KBr) 1703
1
cm-1; H NMR (DMSO-d6) d 8.28-6.98 (m, 11H); EIMS (70
In ad di tion to py ri dines,a -chloroformylarylhydrazine
hydrochloride 1 can also re act with some N-heterocyclic
compounds.3 was ob tained through cycloaddition of 1 with
isoquinoline. Ac cord ing to the struc ture of 3analyzedbyX-
ray spec trum, the re ac tion site of isoquinoline was at the
number1carbonwhichagreedwithmostotherreactions.The
pro duc tion of4, 5, 6 given by cycloaddition of 1 with pyrid-
azine was de pend ent on the re ac tion con di tions. 4 was fa-
vored at lower tem per a tures and a high ra tio of pyridazine. 5
wasobtainedatlowertemperaturesandratioofpyridazine.6
wasgivenathighertemperaturesandratioofpyridazine, and
also ob tained through 4 byenchancingthetemperature. Some
heterocyclic com pounds bear ing a X-C=N (X:S, N) group on
the ring could re act with 1 to gain the de riv a tives of 2,4-
dihydro-1,2,4-triazol-3-one.7, 8, 9 and 10 were given by re-
actionof1 with 1,3,5-triazine, 1,4,5,6-tetrahydropyrimidine,
1,3-thiazole and 2-amino-1,3-thiazole, re spec tively. The re-
ac tions for 2-amino-1,3,4-thiadiazole and 3-amino- 1,2,4-
triazole had the same prod uct11 .
eV) m/z: 261 (M+, 40), 204 (23), 190 (12), 111 (25), 91 (100),
77 (69). Anal. Calcd for C16H11N3O: C, 73.56; H, 4.21; N,
16.09. Found: C, 73.50; H, 4.23; N, 16.01.
2-(p-Methylphenyl)-2H-[1,2,4]triazolo[3,4-a]isoquino-
lin-3-one (3b): col or less nee dles; mp 152-153°C; IR (KBr)
1705 cm-1; 1H NMR (DMSO-d6) d 8.28-6.98 (m, 10H), 2.33
(s, 3H); EIMS (70 eV) m/z: 275 (M+, 100), 218 (20), 204 (10),
128 (23), 91 (42). Anal. Calcd for C17H13N3O: C, 74.18; H,
4.72; N, 15.27. Found: C, 74.15; H, 4.70; N, 15.31.
2-(p-Chlorophenyl)-2H-[1,2,4]triazolo[3,4-a]isoquino-
lin-3-one ( 3c): col or less nee dles; mp 183-183.5°C; IR (KBr)
1708 cm-1; 1H NMR (DMSO-d6) d 8.29-6.99 (m, 10H); EIMS
(70 eV) m/z: 297 (M++2, 31), 295 (M+, 100), 240 (6), 238
(18), 128 (37), 111 (35). Anal. Calcd for C16H10ClN3O: C,
64.98; H, 3.41; Cl, 11.9; N, 14.21. Found: C, 65.04; H, 3.37;
Cl, 11.92; N, 14.24.
Synthesis of 4, 5, 6 from Cycloaddition of 1 with
Pyridazine
Synthesis of 4
EXPERIMENTALSECTION
0.6 g (2.48 mmol)1c and 0.25 g (2.48 mmol) pyridazine
were dis solved in 6 mL isopropyl al co hol and then 0.5 mL
n-Bu3N was added in an ice bath. The mix ture was stirred at
room tem per a ture for 1 hour and then was poured into 150
mL of ice wa ter. The pre cip i tate was dried and recrystalized
from EtOAc + THF to ob tain4c.
2-(p-Chlorophenyl)-2,8a-dihydro-1H-[1,2,4]triazolo-
[4,3-b]pyridazin-3-one (4c): colorless needles; mp 210-
210.5°C; IR (KBr) 3190, 1716 cm-1; 1H NMR (DMSO-d6) d
7.68 (d, J = 9.0 Hz, 2H), 7.42 (d, J = 9.0 Hz, 2H), 7.31-7.28
(m, 1H), 6.78 (d, J = 14.4 Hz, 1H), 6.37-6.17 (m, 2H), 5.22
(dd, J = 2.0, 14.4 Hz, 1H); EIMS (70eV)m/z: 250 (M++2, 15),
248 (M+, 52), 246 (22), 193 (2), 191 (5), 181 (1), 179 (4), 155
(9), 141 (5), 139 (14), 127 (6), 125 (16), 113 (14), 111 (44), 90
(18), 81 (100). Anal. Calcd for C11H9ClN4O: C, 53.13; H,
3.65; Cl, 14.26; N, 22.53. Found: C, 53.14; H, 3.71; Cl,
14.28; N, 22.55.
General
Melting points (Buchi 535 ap pa ra tus) are un cor rected.
IR spec tra were re corded on a Hitachi 270-30 in fra red spectro-
photometer. NMR spec tra were mea sured on a Bruker AMX-
200 NMR spec trom e ter with tetramethylsilane as in ter nal
stan dard. The mass spec tra were reg is tered on a Finnigan
MAT TSQ-46C spec trom e ter at an ion iz ing po ten tial of 70
eV.ElementalanalyseswereperformedonHeraeusCHN-O-
Rapid and Tacussel Coulomax 78 an a lyz ers. X-ray anal y ses
were made with a Nonius CAD-4 diffractometer. Col umn
chromatographywascarriedoutonsilicagel(Kieselgel100,
70-230 mesh, E. Merck).
Synthesis of 3 from Cycloaddition of 1 with Isoquinoline
Isoquinoline was heated to melt ing in hot wa ter and
then the mol ten liq uid (6 mL) was stirred with 0.6 g (2.9
mmol) 1a at 80 °C un der an open sys tem for 2 hours. The re-
action mixture was poured into a 100 mL HCl solution
(HCl/H2O:1/10V/V). Theprecipitatewasrecrystalizedfrom
THF + EtOAc to ob tain 3a. Ac cord ing to this pro ce dure,
cycloaddition re ac tion of var i ous forms of1 with isoquino-
line was achieved.
Synthesis of 5
0.6 g (2.90 mmol) 1a and 0.30 g (2.90 mmol) pyrid-
azine were dis solved in 6 mL isopropyl al co hol and then 0.5
mL n-Bu3N was added in an ice bath. The mix ture was stirred
at 25 °C for 1 hour and then was poured into 150 mL of ice
wa ter. The pre cip i tate was recrystalized from EtOAc + THF
to ob tain5a.Accordingtothisprocedure,cycloadditionreac-
2-Phenyl-2H-[1,2,4]triazolo[3,4-a]isoquinolin-3-one

Reactionofa -Chloroformylarylhydrazine
J. Chin. Chem. Soc., Vol. 49, No. 2, 2002 245
tion of 1b with pyridazine was achieved to give 5b.
C11H7ClN4O: C, 53.56; H, 2.86; Cl, 14.37; N, 22.71. Found:
C, 53.55; H, 2.84; Cl, 14.39; N, 22.66.
2,7-Diphenyl-2,3,3a,5a,6,7-hexahydro-2,3,6,7,8a,8b-
hexaaza-as-indacene-1,8-dione (5a):colorlessneedles;mp
201-201.5 °C; IR (KBr) 3208, 1740 cm -1 ; 1H NMR (DMSO-
d6) d 7.64-7.06 (m, 10H), 7.04 (d, J = 6.4 Hz, 2H), 6.03 (s,
2H), 5.14 (d, J = 6.4 Hz, 2H); EIMS (70 eV) m/z: 348 (M+,
35), 157 (20), 145 (12), 119 (28), 105 (21), 80 (43), 77 (100).
Anal. Calcd for C18H16N6O2: C, 62.06; H, 4.63; N, 24.12.
Found: C, 62.06; H, 4.69; N, 24.10.
Synthesis of 7 from Reaction of 1 with 1,3,5-Triazine
0.6 g (2.90 mmol) 1a and 1.08 g (5.8 mmol) 1,3,5-
triazine were stirred in 6 mL isopropyl al co hol at room tem-
peraturefor2hoursandthenthereactionmixturewaspoured
into 100 mL of ice wa ter. The pre cip i tate was dried and sub-
jected to col umn sep a ra tion (elu tion; EtOAc/hex ane = 1/1).
The isolated compound was recrystalized from EtOAc +
isopropyl al co hol to ob tain7a.Accordingtothisprocedure,
reactionofvariousformsof1 with 1,3,5-triazine was achieved
to give the ex pected prod uct.
2,7-Di(p-methylphenyl)-2,3,3a,5a,6,7-hexahydro-
2,3,6,7,8a,8b-hexaaza-as-indacene-1,8-dione (5b):colorless
nee dles; mp 233-233.5 °C; IR (KBr) 3214, 1731 cm-1; H
1
NMR (DMSO-d6) d 7.48 (d, J = 8.5 Hz, 4H), 7.14 (d, J = 8.5
Hz, 4H), 7.02 (d, J = 6.7 Hz, 2H), 6.01 (s, 2H), 5.09 (d,J = 6.5
Hz, 2H), 2.27 (s, 6H); EIMS (70 eV) m/z: 376 (M+, 50), 171
(30), 159 (19), 105 (45), 91 (100). Anal. Calcd for C20H20N6O2:
C, 63.82; H, 5.36; N, 22.33. Found: C, 63.74; H, 5.37; N,
22.10.
2-Phenyl-2,4-dihydro-1,2,4-triazol-3-one (7a): col or-
less nee dles; mp 178-179 °C; IR (KBr) 3166, 1707, 1683
1
cm-1; H NMR (DMSO-d6) d 11.92 (s, 1H), 8.05 (s, 1H),
7.79-7.23 (m, 5H); EIMS (70 eV)m/z: 161 (M+, 72), 118 (20),
91 (100), 77 (18). Anal. Calcd for C8H7N3O: C, 59.63; H,
4.35; N, 26.09. Found: C, 59.67; H, 4.34; N, 26.14.
Synthesis of 6
2-(p-Methylphenyl)-2,4-dihydro-1,2,4-triazol-3-one
(7b):colorlessneedles;mp164-165°C; IR (KBr) 3154, 1695
cm-1; 1H NMR (DMSO-d6) d 11.90 (s, 1H), 8.07 (s, 1H), 7.74
(d, J = 8.6 Hz, 2H), 7.22 (d, J = 8.6 Hz, 2H), 2.29 (s, 3H);
EIMS (70 eV) m/z: 175 (M+, 53), 132 (11), 105 (100), 91 (18).
0.6 g (2.90 mmol) 1a and 1.16 g (14.5 mmol) pyrid-
azine were stirred in 10 mL isopropyl al co hol at 60 °C for 1
day and then the re ac tion mix ture was poured into 150 mL of
ice wa ter. The pre cip i tate was dried and recrystalized from
EtOAc + THF to ob tain 6a. Ac cord ing to this pro ce dure,
cycloadditionreactionofvariousformsof 1 with pyridazine
was achieved.
Anal. Calcd for C H9N3O: C, 61.70; H, 5.18; N, 23.99.
9
Found: C, 61.74; H, 5.19; N, 23.93.
2-(p-Chlorophenyl)-2,4-dihydro-1,2,4-triazol-3-one
(7c): col or less nee dles; mp > 250 °C; IR (KBr) 3154, 3052,
1695 cm-1; 1H NMR (DMSO-d6) d 12.02 (s, 1H), 8.13 (s, 1H),
7.93 (d, J = 9.0 Hz, 2H), 7.49 (d, J = 9.0 Hz, 2H); EIMS (70
eV) m/z: 197 (M++2, 16), 195 (M+, 50), 154 (3), 152 (9), 127
(31), 125 (100), 113 (5), 111 (16), 90 (38). Anal. Calcd for
C8H6ClN3O: C, 49.12; H, 3.09; Cl, 18.12; N, 21.48. Found: C,
49.12; H, 3.09; Cl, 18.22; N, 21.52.
2-Phenyl-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one
(6a): col or less nee dles; mp 195.5-196°C; IR (KBr) 1725
1
cm-1; H NMR (DMSO-d6) d 8.32 (d, J = 4.0 Hz, 1H), 8.07-
7.28 (m, 5H), 7.91 (d, J = 8.8 Hz, 1H), 7.21 (dd, J = 4.0, 8.8
Hz, 1H); EIMS (70 eV) m/z: 212 (M+, 100), 156 (15), 119 (4),
105 (11), 91 (16), 77 (89). Anal. Calcd for C11H8N4O: C,
62.26; H, 3.77; N, 26.41. Found: C, 62.36; H, 3.79; N, 26.47.
2-p-Methylphenyl-2H-[1,2,4]triazolo[4,3-b]pyridazin-
3-one (6b): col or less nee dles; mp 195-195.5 °C; IR (KBr)
1719 cm-1; 1H NMR (DMSO-d6) d 8.29 (dd, J = 1.3, 4.0 Hz,
1H), 7.93-7.85 (m, 3H), 7.31 (dd,J = 4.0, 9.6 Hz, 1H), 2.33 (s,
3H); EIMS (70 eV) m/z: 226 (M+, 100), 169 (18), 155 (15),
105 (64), 91 (87). Anal. Calcd for C12H10N4O: C, 63.71; H,
4.46; N, 24.76. Found: C, 63.69; H, 4.43; N, 24.73.
Synthesis of 8 from Reaction of 1 with 1,4,5,6-
Tetrahydropyrimidine
0.6 g (2.90 mmol) 1a and 0.24 g (2.90 mmol) 1,4,5,6-
tetrahydropyrimidine were dis solved in 10 mL isopropyl al-
co hol and then 1.62 g (8.70 mmol) n-Bu3N was added. The
mix ture was stirred at 60 °C for 1 hour and then poured into
100 mL of ice wa ter. The pre cip i tate was recrystalized from
EtOAc + isopropyl al co hol to ob tain 8a. Ac cord ing to this
procedure,reactionofvariousformsof 1 with 1,4,5,6- tetra-
hydropyrimidine was achieved.
2-p-Chlorophenyl-2H-[1,2,4]triazolo[4,3-b]pyridazin-
3-one (6c): col or less nee dles; mp 132.5-133°C; IR (KBr)
1
1731 cm-1; H NMR (DMSO-d6) d 8.32 (d, J = 4.0 Hz, 1H),
8.07 (d, J = 9.0 Hz, 2H), 7.89 (d,J = 8.8 Hz, 1H), 7.58 (d, J =
9.0 Hz, 2H), 7.23 (dd,J = 4.0, 8.8 Hz, 1H); EIMS (70 eV) m/z:
248 (M++2, 32), 246 (M+, 100), 155 (39), 141 (3), 139 (12),
127 (6), 125 (19), 113 (24), 111 (75), 91 (15). Anal. Calcd for
4-[3-(2-Phenyl-2,4-dihydro-1,2,4-triazol-3-on-4-yl)-
propyl]-2-phenylsemicarbazide (8a):colorlessneedles;mp
224-225 °C; IR (KBr) 3406, 3322, 3214, 3148, 1692, 1659

246 J. Chin. Chem. Soc., Vol. 49, No. 2, 2002
Chiu et al.
1
cm-1; H NMR (DMSO-d6) d 8.31 (s, 1H), 7.91-6.99 (m,
3328, 1707, 1674 cm-1; 1H NMR (DMSO-d6) d 8.51 (s, 1H),
7.92 (d,J = 9.0 Hz, 2H), 7.66 (d, J = 9.0 Hz, 2H), 7.55 (d, J =
9.0 Hz, 2H), 7.48 (d,J = 9.0 Hz, 2H), 6.80 (d, J = 8.4 Hz, 1H),
6.73 (d,J = 8.4 Hz, 1H), 5.89 (s, 2H); EIMS (70 eV)m/z: 425
(M++4, 2), 423 (M++2, 8), 421 (M+, 11), 365 (4), 363 (25),
361 (37), 282 (3), 280 (8), 256 (5), 254 (36), 252 (72), 197
(4), 195 (9), 171 (6), 169 (17), 155 (16), 153 (48), 143 (30),
141 (100), 113 (20), 111 (60), 90 (20). Anal. Calcd for
C17H13Cl2N5O2S: C, 48.35; H, 3.10; Cl, 16.79; N, 16.58; S,
7.59. Found: C, 48.36; H, 3.20; Cl, 16.79; N, 16.58; S, 7.49.
11H), 5.18 (s, 2H), 3.69 (t, J = 6.3 Hz, 2H), 3.20-3.10 (m,
2H), 1.88-1.82 (m, 2H); EIMS (70 eV) m/z: 352 (M+, 5), 247
(12), 201 (21), 119 (13), 108 (100), 91 (21), 77 (23). Anal.
Calcd for C 18H20N6O2: C, 61.36; H, 5.68; N, 23.86. Found: C,
61.40; H, 5.64; N, 23.82.
4-[3-(2-p-Methylphenyl-2,4-dihydro-1,2,4-triazol-3-
on-4-yl)propyl]-2-p-methylphenylsemicarbazide (8b): col-
or less nee dles; mp > 240 °C; IR (KBr) 3412, 3364, 1683,
1662 cm-1; 1H NMR (DMSO-d6) d 8.27 (s, 1H), 7.62 (d, J =
8.4 Hz, 2H), 7.46-7.40 (m, 3H), 7.24 (d, J = 8.4 Hz, 2H), 7.05
(d, J = 8.4 Hz, 2H), 5.10 (s, 2H), 3.68 (t, J = 6.8 Hz, 2H),
3.18-3.10 (m, 2H), 1.90-1.83 (m, 2H); EIMS (70 eV) m/z: 380
(M+, 7), 258 (30), 203 (43), 175 (15), 122 (100), 105 (40), 91
(35). Anal. Calcd for C20H24N6O2: C, 63.14; H, 6.35; N,
22.09. Found: C, 63.12; H, 6.29; N, 22.14.
4-[3-(2-p-Chlorophenyl-2,4-dihydro-1,2,4-triazol-3-
on-4-yl)propyl]-2-p-chlorophenylsemicarbazide (8c): col or-
less nee dles; mp > 240 °C; IR (KBr) 3400, 3340, 1698, 1662
cm-1; 1H NMR (DMSO-d6) d 8.34 (s, 1H), 7.92 (d, J = 9.0 Hz,
2H), 7.62 (d, J = 9.0 Hz, 2H), 7.60 (br, 1H), 7.51 (d, J = 9.0
Hz, 2H), 7.30 (d,J = 9.0 Hz, 2H), 5.22 (s, 2H), 3.68 (t, J = 6.8
Hz, 2H), 3.19-3.10 (m, 2H), 1.88-1.82 (m, 2H); EIMS (70
eV) m/z: 422 (M++2, 2), 420 (M+, 4), 282 (5), 280 (35), 278
(80), 238 (14), 236 (43), 225 (43), 223 (100), 197 (8), 195
(25), 155 (9), 153 (27), 144 (32), 142 (100), 127 (39), 125 (78),
113 (11), 111 (32), 90 (31). Anal. Calcd for C18H18Cl2N6O2:
C, 51.32; H, 4.31; Cl, 16.83; N, 19.95. Found: C, 51.34; H,
4.36; Cl, 16.86; N, 19.91.
Synthesis of 10 from Reaction of 1 with
2-Amino-1,3-thiazole
0.6 g (2.90 mmol) 1a and 0.87 g (8.70 mmol) 2- amino-
1,3-thiazole were stirred in 6 mL isopropyl al co hol at room
temperaturefor2hoursandthenthemixturewaspouredinto
100 mL of ice wa ter. The pre cip i tate was recrystalized from
EtOAc + isopropyl al co hol to ob tain10a. Ac cord ing to this
procedure, reactionofvariousformsof 1 with 2-amino-1,3-
thiazole was achieved.
(1-p-Methylphenylhydrazino) carboxylic acid (2-(2-p-
methylphenyl-4-amino-2,4-dihydro-1,2,4-triazol-3-on-4-yl)-
vinyl)thiolate (10a): col or less nee dles; mp > 250 °C; IR
(KBr) 3466, 3364, 3304, 3208, 1710, 1671, 1644 cm-1; 1H
NMR (DMSO-d6) d 7.71 (d, J = 8.5 Hz, 2H), 7.46 (d, J = 8.5
Hz, 2H), 7.21-7.17 (m, 4H), 7.01 (d, J = 7.8 Hz, 1H), 6.38 (d,
J = 7.8 Hz, 1H), 6.24 (s, 2H), 5.71 (s, 2H), 2.28 (s, 6H); EIMS
(70 eV) m/z: 396 (M+, 41), 247 (26), 190 (38), 147 (18), 121
(34), 91 (100), 77 (34). Anal. Calcd for C19H20N6O2S: C,
57.56; H, 5.08; N, 21.20; S, 8.09. Found: C, 57.58; H, 5.04;
N, 21.21; S, 8.05.
Synthesis of 9 from Reaction of 1 with 1,3-Thiazole
0.74 g (8.70 mmol) 1,3-thiazole dis solved in 6 mL iso-
propyl al co hol was stirred with 0.6 g (2.90 mmol)1ain an ice
bath for 0.5 hour and then the mix ture was poured into 100
mL of ice wa ter. The pre cip i tate was recrystalized from THF
+isopropylalcoholtoobtain9a.Accordingtothisprocedure,
reactionofvariousformsof1 with 1,3-thiazole was achieved.
(1-Phenylhydrazino) carboxylic acid (2-(2-phenyl-
2,4-dihydro-1,2,4-triazol-3-on-4-yl)vinyl)thiolate(9a): col-
or less nee dles; mp > 250 °C; IR (KBr) 3340, 3274, 3214,
(1-p-Chlorophenylhydrazino) carboxylic acid (2-(2-p-
chlorophenyl-4-amino-2,4-dihydro-1,2,4-triazol-3-on-4-yl)-
vinyl)thiolate (10b): colorless needles; mp > 250 °C; IR
(KBr) 3466, 3346, 3208, 1713, 1647 cm-1; 1H NMR (DMSO-
d6) d 7.86 (d, J = 9.0 Hz, 2H), 7.64 (d,J = 9.0 Hz, 2H), 7.46 (d,
J = 9.0 Hz, 2H), 7.45 (d,J = 9.0 Hz, 2H), 7.01 (d, J = 5.8 Hz,
1H), 6.41 (d, J= 5.8 Hz, 1H), 6.38 (s, 2H), 5.81 (s, 2H); EIMS
(70 eV) m/z: 440 (M++4, 1), 438 (M++2, 5), 436 (M+, 9), 269
(9), 267 (20), 212 (4), 210 (14), 155 (7), 153 (23), 143 (14),
141 (55), 127 (13), 125 (38), 113 (32), 111 (100), 90 (33), 77
(84). Anal. Calcd for C17H14Cl2N6O2S: C, 46.70; H, 3.23; Cl,
16.21; N, 19.22; S, 7.33. Found: C, 46.69; H, 3.22; Cl, 16.21;
N, 19.22; S, 7.30.
1725, 1677 cm-1; H NMR (DMSO-d6) d 8.14 (s, 1H), 7.92-
1
7.13 (m, 10H), 6.81 (d, J = 8.5 Hz, 1H), 6.73 (d, J = 8.5 Hz,
1H), 5.86 (s, 2H); EIMS (70 eV) m/z: 353 (M+, 7), 293 (15),
248 (22), 161 (40), 135 (12), 105 (80), 77 (100). Anal. Calcd
for C 17H15N5O2S: C, 57.78; H, 4.28; N, 19.82; S, 9.07. Found:
C, 57.77; H, 4.30; N, 19.78; S, 9.16.
Synthesis of 11 from Reaction of 1 with
2-Amino-1,3,4-thiadiazole
0.6 g (2.71 mmol) 1b and 0.82 g (8.10 mmol) 2-amino-
1,3,4-thiadiazole were stirred in 6 mL isopropyl al co hol at 60
(1-p-Chlorophenylhydrazino) carboxylic acid (2-(2-
chlorophenyl-2,4-dihydro-1,2,4-triazol-3-on-4-yl)vinyl)-
thiolate (9b): col or less nee dles; mp 224-225 °C; IR (KBr)

Reactionofa -Chloroformylarylhydrazine
J. Chin. Chem. Soc., Vol. 49, No. 2, 2002 247
Table 4. Crystal Data for 3c, 5a, 4c
Compound
3c
5a
C18H16N6O2
348.36
4c
Formula
Fw
C16H10ClN3O
295.73
C11H9ClN4O
248.67
diffractometer used
cryst system
space group
a, Å
b, Å
c, Å
Nonius CAD4
Monoclinic
P21/n
6.1067(21)
16.143(3)
13.8118(20)
-
102.294(17)
-
1330.4(5)
4
Rigaku AFC6S
Triclinic
Rigaku AFC6S
Monoclinic
#
#
P1 ( 2)
P21/c ( 14)
8.6475(9)
10.041(1)
11.115(1)
93.91(1)
110.46(1)
109.45(1)
833.9(2)
2
12.464(2)
11.363(3)
7.759(3)
-
101.33(2)
-
1077.5(5)
4
1.533
a , deg
b, deg
g
, deg
V, Å3
Z
Dcalcd, g cm-3
l (Ka ), Å
F (000)
1.476
0.70930 (Mo)
607.88
1.387
1.54178 (Cu)
364.00
1.54178 (Cu)
512.00
q
no. 2 range, deg
24,12.44-25.42
49.8
25, 78.8-79.9
120.2
25, 78.1-80.1
120.4
2qmax ,deg
scan type
q-2q
w-2q
w- 2q
(K )
0.28mm-1 (Mo)
0.09 ´ 0.12 ´ 0.52
0.891-0.935
298
7.86cm-1 (Cu)
0.20 ´ 0.20 ´ 0.58
0.9184-0.9980
296
30.56cm-1 (Cu)
0.41 ´ 0.41 ´ 0.55
0.7516-0.9980
296
m
a
cryst size, mm
transm factor
temp, K
no. of measd reflns
no. of unique reflns
no. of obsd reflns (No)
2565
2334
1482 (> 2.5 )
0.040, 0.045
1.67
unit weights
0.150
-0.170
2655
2463
2166 (> 3 )
1836
1684
1241 (>3 )
s
s
s
a
Ra, Rw
0.042, 0.051
5.72
0.061, 0.045
6.20
GOFa
weighting scheme
(DQ)max, e-Å-3
(DQ)min, e-Å-3
s 2
s 2
(Fo)]-1
[
(Fo)]-1
[
0.17
-0.28
0.23
-0.31
Table 6. Bond Angles/deg of 2-(p-Chlorophenyl)-2H-
[1,2,4]triazolo[4,3-b]isoquinolin-3-one 3c
°C for 2 hours and then the mix ture was poured into 150 mL
of ice wa ter. The pre cip i tate was recrystalized from THF +
isopropylalcoholtoobtain11a.Accordingtothisprocedure,
reactionofvariousformsof1 with 2-amino-1,3,4-thiadiazole
C(2)-C(1)-C(6)
C(2)-C(1)-Cl
121.0(3)
119.2(3)
119.9(3)
120.0(3)
119.9(3)
119.3(3)
120.4(3)
120.3(3)
120.9(3)
118.9(3)
102.5(3)
130.6(3)
126.9(3)
118.7(3)
129.2(3)
112.1(3)
117.0(3)
122.1(3)
C(10)-C(9)-C(16)
C(9)-C(10)-C(11)
C(9)-C(10)-C(13)
120.9(3)
120.6(3)
117.8(3)
C(6)-C(1)-Cl
C(1)-C(2)-C(3)
C(2)-C(3)-C(4)
C(3)-C(4)-C(5)
C(3)-C(4)-N(1)
C(5)-C(4)-N(1)
C(4)-C(5)-C(6)
C(1)-C(6)-C(5)
N(1)-C(7)-N(2)
N(1)-C(7)-O(7)
N(2)-C(7)-O(7)
C(9)-C(8)-N(2)
C(9)-C(8)-N(3)
N(2)-C(8)-N(3)
C(8)-C(9)-C(10)
C(8)-C(9)-C(16)
C(11)-C(10)-C(13) 121.6(3)
C(10)-C(11)-C(12) 120.6(3)
C(11)-C(12)-N(2)
C(10)-C(13)-C(14) 120.6(4)
C(13)-C(14)-C(15) 121.0(4)
C(14)-C(15)-C(16) 119.9(4)
C(9)-C(16)-C(15)
C(4)-N(1)-C(7)
C(4)-N(1)-N(3)
C(7)-N(1)-N(3)
C(7)-N(2)-C(8)
C(7)-N(2)-C(12)
C(8)-N(2)-C(12)
C(8)-N(3)-N(1)
Table 5. Bond Distances/Å of 2-(p-Chlorophenyl)-2H-
[1,2,4]triazolo[4,3-b]isoquinolin-3-one 3c
119.0(4)
C(1)-C(2)
C(1)-C(6)
C(1)-Cl
1.367(5)
1.388(5)
1.739(3)
1.376(5)
1.394(5)
1.380(5)
1.413(4)
1.376(5)
1.372(4)
1.390(4)
1.217(4)
1.449(4)
C(8)-N(2)
C(8)-N(3)
1.371(4)
1.299(4)
1.407(4)
1.389(5)
1.453(5)
1.409(5)
1.332(6)
1.392(4)
1.369(7)
1.384(6)
1.382(5)
1.398(3)
C(9)-C(10)
C(9)-C(16)
C(10)-C(11)
C(10)-C(13)
C(11)-C(12)
C(12)-N(2)
C(13)-C(14)
C(14)-C(15)
C(15)-C(16)
N(1)-N(3)
119.9(3)
127.5(3)
119.6(2)
112.9(2)
108.6(2)
127.3(3)
124.0(3)
103.9(2)
C(2)-C(3)
C(3)-C(4)
C(4)-C(5)
C(4)-N(1)
C(5)-C(6)
C(7)-N(1)
C(7)-N(2)
C(7)-O(7)
C(8)-C(9)

248 J. Chin. Chem. Soc., Vol. 49, No. 2, 2002
Chiu et al.
Table 7. Bond Lengths/Å of 2-(p-Chlorophenyl)-2,8a-dihydro-
1H-[1,2,4]triazolo[4,3-b]pyridazin-3-one 4c
Table 9. Bond Lengths/Å of 2,7-Diphenyl-2,3,3a,5a,6,7-
hexahydro-2,3,6,7,8a,8b-hexaaza-as-indacene-1,8-dione
5a
Cl(1)-C(9)
N(1)-N(2)
N(1)-C(6)
N(3)-C(1)
N(4)-C(5)
C(6)-C(7)
C(7)-C(8)
C(8)-C(9)
C(9)-C(10)
O(1)-C(1)
1.748(4)
1.438(5)
1.424(5)
1.357(5)
1.283(6)
1.389(6)
1.396(6)
1.367(6)
1.358(7)
1.226(5)
N(1)-C(1)
N(2)-C(2)
N(3)-N(4)
N(3)-C(2)
C(2)-C(3)
C(3)-C(4)
C(4)-C(5)
C(6)-C(11)
C(10)-C(11)
1.360(5)
1.442(5)
1.358(4)
1.454(6)
1.477(6)
1.318(6)
1.435(8)
1.377(6)
1.389(6)
O(1)-C(1)
N(1)-N(2)
N(1)-C(7)
N(3)-C(1)
N(4)-N(5)
N(4)-C(13)
N(6)-C(6)
C(7)-C(8)
C(8)-C(9)
C(9)-C(10)
C(10)-C(11)
C(11)-C(12)
C(13)-C(18)
O(2)-C(2)
N(1)-C(1)
1.213(3)
1.443(3)
1.413(3)
1.406(3)
1.446(3)
1.413(3)
1.471(3)
1.380(4)
1.386(4)
1.367(4)
1.371(4)
1.385(4)
1.382(4)
1.213(3)
1.353(3)
N(2)-C(3)
N(3)-N(6)
N(3)-C(3)
N(4)-C(2)
N(5)-C(6)
N(6)-C(2)
C(3)-C(4)
C(4)-C(5)
C(5)-C(6)
C(7)-C(12)
C(13)-C(14)
C(14)-C(15)
C(15)-C(16)
C(16)-C(17)
C(17)-C(18)
1.469(3)
1.404(3)
1.471(3)
1.353(3)
1.464(3)
1.398(3)
1.492(4)
1.321(4)
1.492(4)
1.383(4)
1.392(4)
1.382(4)
1.374(5)
1.377(5)
1.384(4)
Table 8. Bond Angles/deg of 2-(p-Chlorophenyl)-2,8a-dihydro-
1H-[1,2,4]triazolo[4,3-b]pyridazin-3-one 4c
N(2)-N(1)-C(1)
C(1)-N(1)-C(6)
N(4)-N(3)-C(1)
C(1)-N(3)-C(2)
O(1)-C(1)-N(1)
N(1)-C(1)-N(3)
N(2)-C(2)-C(3)
N(3)-C(2)-C(3)
C(3)-C(4)-C(5)
N(1)-C(6)-C(7)
C(7)-C(6)-C(11)
C(7)-C(8)-C(9)
Cl(1)-C(9)-C(10)
117.3(3)
129.4(4)
123.9(4)
110.8(4)
127.8(4)
105.1(4)
117.2(4)
108.6(4)
120.1(5)
120.4(4)
119.8(4)
119.7(5)
119.3(4)
N(2)-N(1)-C(6)
N(1)-N(2)-C(2)
N(4)-N(3)-C(2)
N(3)-N(4)-C(5)
O(1)-C(1)-N(3)
N(2)-C(2)-N(3)
C(2)-C(3)-C(4)
N(4)-C(5)-C(4)
N(1)-C(6)-C(11)
C(6)-C(7)-C(8)
Cl(11)-C(9)-C(8)
C(8)-C(9)-C(10)
118.8(4))
102.4(3)
124.4(4)
112.5(4)
127.0(4)
102.2(4)
117.0(5)
125.3(5)
119.7(5)
118.9(5)
118.7(4)
122.0(4)
Table 10. Bond Angles/deg of 2,7-Diphenyl-2,3,3a,5a,6,7-
hexahydro-2,3,6,7,8a,8b-hexaaza-as-indacene-1,8-
dione 5a
N(2)-N(1)-C(1)
C(1)-N(1)-C(7)
N(6)-N(3)-C(1)
C(1)-N(3)-C(3)
N(5)-N(4)-C(13)
N(4)-N(5)-C(6)
N(3)-N(6)-C(6)
O(1)-C(1)-N(1)
N(1)-C(1)-N(3)
O(2)-C(2)-N(6)
N(2)-C(3)-N(3)
C(3)-C(4)-C(5)
N(5)-C(6)-N(6)
N(1)-C(7)-C(8)
C(8)-C(7)-C(12)
C(8)-C(9)-C(10)
111.8(2) N(1)-N(2)-C(3)
128.3(2) N(6)-N(3)-C(3)
112.9(2) N(5)-N(4)-C(2)
107.0(2) C(2)-N(4)-C(13)
118.2(2) N(3)-N(6)-C(2)
102.4(2) C(2)-N(6)-C(6)
116.3(2) O(1)-C(1)-N(3)
128.0(3) O(2)-C(2)-N(4)
106.9(2) N(4)-C(2)-N(6)
125.1(2) N(2)-C(3)-C(4)
102.8(2) N(3)-C(3)-C(4)
123.2(3) C(4)-C(5)-C(6)
102.8(2) N(5)-C(6)-C(5)
120.8(2) N(6)-C(6)-C(5)
120.2(2) N(1)-C(7)-C(12)
121.1(3) C(7)-C(8)-C(9)
102.6(2)
116.9(2)
111.9(2)
129.3(2)
115.4(2)
107.5(2)
125.1(2)
128.1(2)
106.7(2)
113.4(2)
111.8(2)
122.8(3)
113.1(2)
111.5(2)
119.0(2)
119.1(3)
119.4(3)
119.4(3)
119.2(3)
C(6)-C(11)-C(10) 120.8(5)
C(9)-C(10)-C(11) 118.7(5)
was achieved.
Synthesis of 11 from Reactionof 1 with
3-Amino-1,2,4-triazole
0.6 g (2.90 mmol) 1a and 0.69 g (8.10 mmol) 3-amino-
1,2,4-triazole were stirred in 6 mL isopropyl al co hol at 60°C
for 2 hours and then the mix ture was poured into 150 mL of
ice water. The precipitate was recrystalized from THF +
isopropylalcoholtoobtain11a.Accordingtothisprocedure,
re ac tion of var i ous forms of 1 with 3-amino-1,2,4-triazole
was achieved.
C(10)-C(11)-C(12) 120.7(3) C(9)-C(10)-C(11)
N(4)-C(13)-C(14) 120.4(2) C(7)-C(12)-C(11)
C(14)-C(13)-C(18) 120.4(3) N(4)-C(13)-C(18)
C(14)-C(15)-C(16) 120.9(3) C(13)-C(14)-C(15) 119.2(3)
N(2)-N(1)-C(7) 119.7(2) C(15)-C(16)-C(17) 119.4(3)
C(16)-C(17)-C(18) 121.1(3) C(13)-C(18)-C(17) 119.1(3)
5-Amino-bis(2-phenyl-2,4-dihydro-1,2,4-triazol-3-on-
4-yl) (11a): col or less nee dles; mp > 250 °C; IR (KBr) 3340,
3184, 1716 cm-1; 1H NMR (DMSO-d6) d 8.76(s, 1H), 7.90-
7.14 (m, 10H), 7.02 (s, 2H); EIMS (70 eV)m/z: 335 (M+, 40),
175 (20), 119 (11), 105 (23), 91 (21), 77 (100). Anal. Calcd
for C16H13N7O22: C, 57.31; H, 3.88; N, 29.25. Found: C,
57.36; H, 3.86; N, 29.31.
(KBr) 3352, 3184, 1716 cm-1; 1H NMR (DMSO-d6) d 8.76 (s,
1H), 7.75 (d, J= 8.4 Hz, 2H), 7.68 (d,J = 8.4 Hz, 2H), 7.32 (d,
J = 8.4 Hz, 2H), 7.24 (d,J = 8.4 Hz, 2H), 6.97 (s, 2H), 2.33 (s,
3H), 2.29 (s, 3H); EIMS (70 eV) m/z: 363 (M+, 20), 189 (12),
175 (12), 119 (31), 91 (100). Anal. Calcd for C18H17N7O2: C,
59.60; H, 4.72; N, 26.98. Found: C, 59.41; H, 4.76; N, 26.89.
5-Amino-bis(2-p-chlorophenyl-2,4-dihydro-1,2,4-
triazol-3-on-4-yl) (11c): col or less nee dles; mp > 250°C; IR
5-Amino-bis(2-p-methylphenyl-2,4-dihydro-1,2,4-
triazol-3-on-4-yl) (11b): col or less nee dles; mp > 250°C; IR

Reactionofa -Chloroformylarylhydrazine
J. Chin. Chem. Soc., Vol. 49, No. 2, 2002 249
(KBr) 3352, 3184, 1719, 1668 cm-1; 1H NMR (DMSO-d6) d
8.79 (s, 1H), 7.91 (d, J= 9.0 Hz, 2H), 7.82 (d,J = 9.0 Hz, 2H),
7.60 (d, J = 9.0 Hz, 2H), 7.51 (d, J = 9.0 Hz, 2H), 7.09 (s, 2H);
EIMS (70 eV) m/z: 394 (M++4, 12), 392 (M++2, 72), 390 (M+,
98), 211 (10), 209 (31), 155 (2), 153 (7), 127 (8), 125 (25),
113 (34), 111 (100). Anal. Calcd for C16H11Cl2N7O2: C,
47.54; H, 2.74; Cl, 17.54; N, 24.26. Found: C, 47.58; H, 2.71;
Cl, 17.52; N, 24.29.
1,4,5,6-Tetrahydropyrimidine; 1,3-Thiazole;
2-Amino-1,3-thiazole; 2-Amino-1,3,4-thiadiazole;
3-Amino-1,2,4-triazole.
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ACKNOWLEDGMENT
WethanktheNationalScienceCounciloftheRepublic
of China for fi nan cial sup port of this study.
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Key Words
a -Chloroformylarylhydrazine hydrochloride;
Pyridines; 2-Aryl-2H-[1,2,4]triazolo[4,3-a]pyridin-
3-ones; Cycloaddition; N-heterocyclic compounds;
Isoquinoline; Pyridazine; 1,3,5-Triazine;