Reactions with hydrazonoyl halides 63: Synthesis and anticancer activity of some new 1,3,4-thiadiazoles, 1,3,4-selenadiazoles, and 1,2,4-triazolo[4,3-a] pyrimidines

Article abstract of DOI:10.1080/10426500903348013

2,3-Dihydro-1,3,4-thiadiazoles, 2,3-dihydro-1,3,4-selenadiazoles, and triazolino[4,3-a]pyrimidines containing benzoxazole or benzothiazole moieties were prepared from the reaction of each of ethyl 3-aza-3-(benzoxazol-2-ylamino)- 2-chloroprop-2-enoate and ethyl 3-aza-3-(benzothiazolo-2-ylamino)-2-chloroprop- 2-enoate with each of potassium thiocyanate, potassium selenocyanate, alkyl carbodithioate, and pyrmidine-2-thione derivatives. All the newly synthesized compounds were confirmed by elemental analysis, spectral data, and alternative route synthesis whenever possible. Some of the newly synthesized compounds were screened toward certain cancer tumors. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright

Full text of DOI:10.1080/10426500903348013

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Reactions with Hydrazonoyl Halides 63:
Synthesis and Anticancer Activity of
Some New 1,3,4-Thiadiazoles, 1,3,4-
Selenadiazoles, and 1,2,4-Triazolo[4,3-
a]pyrimidines
Eman K. A. Abdelall a , Mahmoud A. Mohamed b & Abdou O.
Abdelhamid c
a Department of Pharmaceutical Organic Chemistry , Faculty of
Pharmacy, Beni-Suef University , Beni-Suef, Egypt
b Department of Textile , Faculty of Industrial Education, Beni-Suef
University , Beni-Suef, Egypt
c Department of Chemistry , Faculty of Science, Cairo University ,
Giza, Egypt
Published online: 25 Aug 2010.
To cite this article: Eman K. A. Abdelall , Mahmoud A. Mohamed & Abdou O. Abdelhamid (2010)
Reactions with Hydrazonoyl Halides 63: Synthesis and Anticancer Activity of Some New 1,3,4-
Thiadiazoles, 1,3,4-Selenadiazoles, and 1,2,4-Triazolo[4,3-a]pyrimidines, Phosphorus, Sulfur, and
Silicon and the Related Elements, 185:9, 1862-1874, DOI: 10.1080/10426500903348013
To link to this article: http://dx.doi.org/10.1080/10426500903348013
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Phosphorus, Sulfur, and Silicon, 185:1862–1874, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903348013
REACTIONS WITH HYDRAZONOYL HALIDES 63:
SYNTHESIS AND ANTICANCER ACTIVITY OF SOME NEW
1,3,4-THIADIAZOLES, 1,3,4-SELENADIAZOLES, AND
1,2,4-TRIAZOLO[4,3-a]PYRIMIDINES
Eman K. A. Abdelall,1 Mahmoud A. Mohamed,2
and Abdou O. Abdelhamid3
1Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy,
Beni-Suef University, Beni-Suef, Egypt
2Department of Textile, Faculty of Industrial Education, Beni-Suef University,
Beni-Suef, Egypt
3Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
2,3-Dihydro-1,3,4-thiadiazoles, 2,3-dihydro-1,3,4-selenadiazoles, and triazolino[4,3-
a]pyrimidines containing benzoxazole or benzothiazole moieties were prepared from
the reaction of each of ethyl 3-aza-3-(benzoxazol-2-ylamino)-2-chloroprop-2-enoate and
ethyl 3-aza-3-(benzothiazolo-2-ylamino)-2-chloroprop-2-enoate with each of potassium
thiocyanate, potassium selenocyanate, alkyl carbodithioate, and pyrmidine-2-thione
derivatives. All the newly synthesized compounds were confirmed by elemental analysis,
spectral data, and alternative route synthesis whenever possible. Some of the newly
synthesized compounds were screened toward certain cancer tumors.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Anticancer activity; hydrazonoyl bromide; 1,3,4-selenadiaziles; 1,3,4-thiadiazoles;
triazolo[4,3-a]pyrimidines
INTRODUCTION
Hydrazonoyl halides have been widely employed for the synthesis of heterocyclic
compounds.1–4 1,3,4-Thiadiazole derivatives have become useful in medicine, agriculture,
and in many fields of technology.5 In addition, 2-(4-aminophenyl)benzothiazole and oxa-
zole and their analogues are a novel class of potent and selective antitumor agents.6–10 As an
extension of our study11–16 and of our synthesis of 1,3,4-thiadiazoles, we report here the syn-
thesis of hydrazonoyl halides containing 4-phenylbenzothiazole and 4-phenylbenzoxazole
moieties and their reactions toward some potassium thiocyanate, potassium selenocyanate,
alkyl carbodithioate, and pyrimidine-2-thione derivatives.
Received 1 June 2009; accepted 18 September 2009.
Address correspondence to Abdou O. Abdelhamid, Department of Chemistry, Faculty of Science, Cairo
University, Giza 12613, Egypt. E-mail: aabdou abdelhamid@yahoo.com
1862

REACTIONS WITH HYDRAZONOYL HALIDES
1863
RESULTS AND DISCUSSION
Treatment of the appropriate diazotized [4-(1,3-benzoxazol-2-yl)phenyl]amine6
(1a) and diazotized [4-(1,3-benzothiazol-2-yl)phenyl]amine10 (1b) with ethyl 2-
chloro-3-oxobutanoate in ethanolic sodium acetate gave ethyl 3-aza-3-[(benzoxazol-
2-ylphenyl)amino]-2-chloroprop-2-enoate (2a) and ethyl 3-aza-3-(benzothiazolo-2-
ylphenyl)amino]-2-chloroprop-2-enoate (2b), respectively. Structure 2 was elucidated
1
by elemental analysis and spectral data. The H NMR spectrum of 2a showed signals
at δ = 1.37 (t, 3H, J = 7.5 Hz, CH2CH3), 4.35 (q, 2H, J = 7.5 Hz, CH2CH3),
7.40 (d, 2H, J = 8Hz, ArH’s), 7.50 (d, 2H, J = 8Hz, ArH’s), 8.00 (d, 2H, J = 8Hz,
ArH’s), 8.07 (d, 2H, J = 8Hz, ArH’s), and 10.89 (s, br., 1H, NH). Treatment of the
appropriate 2a with each of potassium thiocyanate and potassium selenocyanate gave
ethyl 3-(4-(benzoxazol-2-ylphenyl)-2-imino-1,3,4-thiadiazoline-5-carboxylate (4a) and
ethyl 3-(4-(benzoxazol-2-ylphenyl)-2-imino-1,3,4-selenadiazoline-5-carboxylate (4c),
respectively (Scheme 1). The structure of 4 was elucidated on the basis of elemental
analyses, spectral data, alternative synthetic route, and its nitrosation and acylation
reactions.
N
Y
+
C2H5O2C
Cl
-
CH3COCH(Cl)CO2C2H5
+
N2 Cl
Ar =
N
2
NH
Ar
1a, Y = O
1b, Y = S
1,2a, Ar = 4-benzoxazol-2-ylphenyl
b, Ar = 4-benzothiazol-2-ylphenyl
O
O
XCN
2 + KXCN
O
X
O
O
N-N=O
N
X
N
O
O
NH
Ar
N
O
(NH2)CS
O
N
X
Ar
5a-c
N
3a-c
Ar
S
NH2
NH
7a-c
O
O
N
NH
6
X
O
NH
O
NR
N
Ar
N
N
N
- NH3
Ar
Ar
4a,b
4a, X = S
4b, X = S
4c, X = Se
8,9(a-c)
(3-9)a, Ar = 4-benzoxazol-2-ylphenyl, X = S
(3-9)b, Ar = 4-benzothiazol-2-ylphenyl, X = S
(3-9)c, Ar = 4-benzoxazol-2-ylphenyl, X = Se
8, R = COCH3
9, R = COC6H4CH3-p
Scheme 1
In addition, treatment of the appropriate 2a with thiourea in boiling ethanol gave
a product identical in all respects (mp, mixed mp, and spectra) with 4a. These results
indicate that hydrazone 3a and amidiazone 6a are not the final products, and that 3a and
6a readily gave 4a either by cyclization or by elimination of one molecule of ammonia
(Scheme 1). Acylation of 4a with acetic anhydride or with 4-methylbenzoyl chloride
in pyridine afforded ethyl 2-(1-aza-2-oxopropylidene)-3-(4-benzoxazol-2-ylphenyl)-1,3,4-
thiadiazoline-5-carboxylate (8a) and ethyl 2-[1-aza-2-(4-methylphenyl)-2-oxoethylidene]-
3-(4-benzoxazol-2-ylphenyl)-1,3,4-thiadiazoline-5-carboxylate (9a), respectively. Spectral
1
data and elemental analyses confirmed their structures. H NMR spectrum of 8a showed

1864
E. K. A. ABDELALL ET AL.
signals at δ = 1.45 (t, 3H, J = 7.5 Hz, CH2CH3), 2.41 (s, 3H, CH3CON ), 4.47(q, 2H,
J = 7.5 Hz, CH2CH3), 7.40 (d, 2H, J = 8Hz, ArH’s), 7.50 (d, 2H, J = 8Hz, ArH’s), and
8.44 (d, 2H, J = 8Hz, ArH’s).
Analogously, acylation of each of 4b and 4c gave 8b,c and 9b,c, respectively.
Nitrosation of each 4a and 4c with saturated sodium nitrite in acetic acid at 0–5◦C
gave ethyl 2-(azanitrosomethylene)-3-(benzoxazol-2-ylphenyl)-1,3,4-thiadiazoline-5-
carboxylate (5a) and ethyl 2-(azanitrosomethylene)-3-(benzoxazol-2-ylphenyl)-1,3,
4-selenadiazoline-5-arboxylate (5c), respectively. Ethyl 3-(4-benzoxazol-2-ylphenyl)-2-
oxo-1,3,4-thia/selenadiazoline-5-carboxylate 7a,c and 3-(4-benzothiazol-2-ylphenyl)-2-
oxo-1,3,4-thiadiazoline-5-carboxylate 7b were prepared by thermolysis of 5a,c and 5b in
boiling xylene. The IR spectrum of 7 revealed a band near ν = 1685 cm−1 (CO).
Compound 2a reacted with the methyl carbodithioates18,19 10a to give the 1,3,4-
thiadiazoline derivative 13a. The structure of 13a was confirmed by elemental analysis,
1
spectral data, and alternative synthetic route. H NMR of 13a showed signals at δ =
1.36(t, 3H, CH3CH2), 4.39 (q, 2H, CH2CH3), 7.54–8.33 (m, 13H, ArH’s), and 8.57 CH
(vinyl)). Also, treatment of 2a with ethyl carbodithioates 11a in ethanolic triethylamine
gave a product identical in all respects (mp, mixed mp, and spectra) with 13a. Product 13a
was assumed to be formed via elimination of alkanethiol (R1SH) from the corresponding
cycloadduct 15, which formed from 1,3-dipolar cycloaddition (or 1,3-addition) of nitrile
imide 16 (generated in situ from hydrazonoyl chlorides 2 and triethylamine) to C S 14
(Scheme 2). Analogously, treatment of the appropriate 2a,b with the appropriate 10a–g (or
11a–g) in ethanolic triethylamie gave the thiadiazolines 13a–g and 14 a–g, respectively
(Scheme 2).
Next, treatment of ethyl 4-methyl-6-phenyl-2-thioxo-1,3,6-trihydro-pyrimidine-5-
carboxylate (17a) with 2a in chloroform and triethylamine gave the 1,2,4-triazolo[4,3-
a]pyrimidine-5-carboxylates 20a. The structure of 20a was elucidated by elemental analy-
sis, spectra, and alternative synthesis. The 1H NMR spectrum of 20a showed signals at δ =
1.23 (t, 3H, CH3CH2), 1.12 (t, 3H, CH3CH2), 2.88 (s, 3H, CH3), 4.02 (q, 2H, CH2CH3),
4.11 (q, 2H, CH2CH3), 6.67 (s, 1H, CH), and 6.8–8.43 (m, 13H, ArH). Its IR spectrum
revealed bands at ν = 1735 cm−1 (CO). Ethyl 6-methyl-4-[4-phenyl-2-methylthio-3,4-
dihydropyrimidine-5-carboxylate (22a) reacted with 2a in boiling ethanolic sodium ethox-
ide solution gave products identical in all aspects (mp, mixed mp, and spectra) with the
corresponding 20a. Analogously, treatment of each 2a with the appropriate 17b,c and 2b
with the appropriate 17a–c gave triazolo[4,3-a]pyrimidines 20b,c and 21a–c, respectively
(Scheme 3).
The formation of 20 can be explained via 1,3-dipolar cycloaddition or 1,3-addition
of nitrile imide 16 (prepared in situ from hydrazonoyl chlorides 2 with triethylamine or
sodium ethoxide) to C S of 16 (or NH of 22) to give intermediate 18 (or 23), with ring
opening and ring closure to afford the final products 20 by elimination of hydrogen sulfide
from 19 (or methyl mercaptan from 23) (Scheme 3).
Treatment of 2a with methyl benzoylhydrazinecarbodithioate (24) in ethanolic tri-
ethylamine gave 2,3-dihydro-1,3,4-thiadiazole 26 (Scheme 4). Its structure was elucidated
by elemental analysis, spectral data, and alternative synthetic route. The 1H NMR spectrum
showed signals at δ = 1.39 (t, 3H, CH3CH2), 4.42 (q, 2H, CH3CH2), 7.42–8.35 (m, 13H,
ArH), and 11.42 (s, br, 1H, NH). Thus, treatment of 2a with 5-phenyl-1,3,4-oxadiazole-
2-thiol (27) gave products identical in all respects (mp, mixed mp, and spectra) with 26a
(Scheme 4). Similarly, treatment of the appropriate 2a,b with 28 gave thiadiazolines 29a
and 29b, respectively.

REACTIONS WITH HYDRAZONOYL HALIDES
1865
R'''
O
N
N
R''
Et3N
R''
S
2a,b
+
NNHCSSR'
O
R'''
SR'
N
NH
Ar
10a-g, R' = CH3
11a-g, R' = C2H5
O
11
+
O
- R'SH
O
O
10
-
N
N
O
S
SR'
16
Ar
R'''
S
N
N
O
N
- R'SH
NHN=CR"R"'
N
N
R''
N
Ar
Ar
13, 14
11a, R'' = H, R''' = C6H5, R' = C2H5
15
10a, R'' = H, R''' = C6H5 , R' = CH3
b, R'' = H, R''' = 2,3-(OCH2O)C6H3, R' = C2H5
c, R'' = H, R''' = 4-(CH3)2CHC6H4, R' = C2H5
d, R'' = CH3, R''' = C6H5, R' = C2H5
b, R'' = H, R''' = 2,3-(OCH2O)C6H3, R' = CH3
c, R'' = H, R''' = 4-(CH3)2CHC6H4, R' = CH3
d, R'' = CH3, R''' = C6H5, R' = CH3,
e, R'' = CH3, R''' = 2-C4H3O, R' = C2H5
f, R''-R''' = 1,2-C6H4(NHCOC=), R' = C2H5
g, R''-R''' =1,2-C6H4(COC=CO), R' = C2H5
e, R'' = CH3, R''' = 2-C4H3O, R' = CH3
f, R''-R''' = 1,2-C6H4(NHCOC=), R' = CH3
g, R''-R''' =1,2-C6H4(COC=CO), R' = CH3
13a, R'' = H, R''' = C6H5, Ar = 4-benzoxazol-2-ylphenyl
b, R'' = H, R''' = 2,3-(OCH2O)C6H3, Ar = 4-benzoxazol-2-ylphenyl
c, R'' = H, R''' = 4-(CH3)2CHC6H4, Ar = 4-benzoxazol-2-ylphenyl
d, R'' = CH3, R''' = C6H5, Ar, Ar = 4-benzoxazol-2-ylphenyl
e, R'' = CH3, R''' = 2-C4H3O, Ar = 4-benzoxazol-2-ylphenyl
f, R''-R''' = 1,2-C6H4(NHCOC=), Ar = 4-benzoxazol-2-ylphenyl
g, R''-R''' = 1,2-C6H4(COC=CO), Ar = 4-benzoxazol-2-ylphenyl
14a, R'' = H, R''' = C6H5, Ar = 4-benzothiazol-2-ylphenyl
b, R'' = H, R''' = 2,3-(OCH2O)C6H3, Ar = 4-benzothiazol-2-ylphenyl
c, R'' = H, R''' = 4-(CH3)2CHC6H4, Ar, Ar = 4-benzothiazol-2-ylphenyl
d, R'' = CH3, R''' = C6H5, Ar, Ar = 4-benzothiazol-2-ylphenyl
e, R'' = CH3, R''' = 2-C4H3O, Ar = 4-benzothiazol-2-ylphenyl
f, R''-R''' = 1,2-C6H4(NHCOC=), Ar = 4-benzothiazol-2-ylphenyl
g, R''-R''' =1,2-C6H4(COC=CO), Ar = 4-benzothiazol-2-ylphenyl
Scheme 2
ANTICANCER AND CYTOTOXIC ACTIVITY
Twelve of the synthesized compounds were subjected to anticancer screening, and
some of these compounds showed a cytotoxic effect. Female Swiss albino mice from the
Animal House of the Egyptian Cancer Institute were maintained on standard pellet diet and
water, and in vitro test for cytotoxic effect was operated using Ehrlich ascites carcinoma
(EAC)17 induced through interperitonial transplantation in female Swiss albino mice. (See
the Supplemental Materials, available online, for full details.)
EXPERIMENTAL
All melting points were determined on an electrothermal apparatus and are uncor-
rected. IR spectra were recorded (KBr discs) on a Shimadzu FT-IR 8201 PC spectropho-
1
tometer. H NMR spectra were recorded in CDCl3 and (CD3)2SO solutions on a Varian

1866
E. K. A. ABDELALL ET AL.
R'
R'
C2H5O2C
Ar
N
NH
C2H5O2C
N
NH
or
2
15
+
N
H
S
N
H
S
18
CO2C2H5
17a-c
O
R'
N
R'
CO2C2H5
NNHAr
R'
N
C
S
OC2H5
C2H5O2C
C2H5O2C
C2H5O2C
NH
NH
+
2
N
NH
SCH3
N
N
SCH3
Ar
22
19
23
17a, R' = C6H5
b, R' = 3,4-(OCH3)2C6H3
c, R' = 2,3-(O-CH2-O)2C6H3
- H2S
R'
CO2C2H5
C2H5O2C
20a, R' = C6H5, Ar = 4-benzoxazol-2-ylphenyl
b, R' = 3,4-(OCH3)2C6H3, Ar = 4-benzoxazol-2-ylphenyl
c, R' = 2,3-(O-CH2-O)C6H3, Ar = 4-benzoxazol-2-ylphenyl
N
N
N
N
Ar
20, 21
21a, R' = C6H5, Ar = 4-benzothiazol-2-ylphenyl
b, R' = 3,4-(OCH3)2C6H3, Ar = 4-benzothiazol-2-ylphenyl
c, R' = 2,3-(O-CH2-O)C6H3, Ar = 4-benzothiazol-2-ylphenyl
Scheme 3
Gemini 300 MHz spectrometer, and chemical shifts were expressed in δ units using TMS
as internal reference. Elemental analyses were carried out at the Microanalytical Center of
the Cairo University. Alkyl carbodithioates18,19 were prepared as previously reported.
Synthesis of Ethyl 3-Aza-3-(benzoxazol-2-ylamino)-2-chloroprop-2-
enoate (2a) and Ethyl 3-Aza-3-(benzothiazolo-2-ylamino)-2-
chloroprop-2-enoate (2b)
The appropriate amount of diazotized [4-(1,3-benzoxazol-2-yl)phenyl]amine (1a)
and diazotized [4-(1,3-benzothiazol-2-yl)phenyl]amine (1b) (0.005 mol) were added drop-
wise to cold solution (0◦C) of ethyl 2-chlorobutanoate (1.65 g, 0.005 mol) and sodium
acetate trihydrate (0.65 g, 0.005 mol) while stirring. The yellow precipitate was collected
and recrystallized from ethanol to give 2a and 2b, respectively (Tables I and II).
C2H5O2C
S
C2H5O2C
- CH3SH
NHNHCOPh
SCH3
Et3N
S
2 +
PhCONHNHCSSCH3
N
NNHCOPh
N
N
14
N
Ar
Ar
25
C6H5NHC(S)SCH3 / Et3N
26
Ar, a = 4-benzoxazol-2-ylphenyl
Ar, b = 4-benzothiazol-2-ylphenyl
28
2 / Et3N
C2H5O2C
S
NH
N
NC6H5
N
S
N
O
Ph
Ar
27
29
Scheme 4

REACTIONS WITH HYDRAZONOYL HALIDES
1867
Table I Characterization data of the newly synthesized compounds
% Analyses, Calcd./Found
Mol. Formula
Mol. Wt.
Yielda%
Color
Mp, ◦C
Solvent
Compound
no.
S
N
H
C
—
12.22
12.02
11.68
11.79
15.29
15.32
14.65
14.65
13.56
13.50
17.71
17.65
17.02
16.99
15.83
15.75
11.44
11.41
10.96
11.01
10.14
9.86
13.72
13.69
13.20
13.30
12.30
12.36
11.56
11.39
11.19
11.22
10.54
10.39
14.92
14.79
13.64
13.59
13.69
13.66
14.48
14.45
14.79
14.66
16.46
16.33
13.38
13.31
14.42
14.31
4.10
3.99
3.92
3.99
3.85
3.77
3.69
3.80
3.41
3.32
3.31
3.22
3.18
3.10
2.96
3.01
3.57
3.77
3.42
3.32
3.16
3.11
3.95
3.79
3.80
3.87
3.54
3.44
4.16
4.17
4.03
4.11
3.79
3.63
4.08
4.01
3.73
3.66
4.93
4.90
4.38
4.33
4.04
4.00
3.55
3.49
3.27
3.11
3.94
3.79
59.40
59.23
56.74
56.59
59.01
59.12
56.53
56.66
52.31
52.32
54.68
54.60
52.54
52.44
48.88
48.75
58.85
58.77
56.38
56.30
52.19
52.09
58.81
58.79
56.59
56.55
52.76
52.59
64.45
64.39
62.38
62.40
58.76
58.59
63.95
63.75
60.81
60.77
65.74
65.59
64.58
64.52
60.88
60.95
61.17
61.09
61.94
61.70
61.84
61.77
C17H14ClN3O3
343.76
82
Yellow
80
Orange
60
Brown
60
Brown
65
Brown
85
Red
80
Pale rose
80
Pale rose
60
Shiny yellow
65
Shiny yellow
60
Shiny yellow
85
Buff
80
Buff
80
Buff
90
Buff
85
Buff
85
Buff
75
Yellow
76
Yellow
75
Yellow
65
Yellow
70
Yellow
72
199–201
EtOH
172–174
EtOH
170–174
EtOH
165–168
EtOH
2a
2b
8.91
9.01
8.75
8.59
16.77
16.70
—
C
17H14ClN3O2S
359.83
18H14N4O3S
366.39
18H14N4O2S2
382.46
18H14N4O3Se
413.29
18H13N5O4S
395.39
18H13N5O3S2
411.46
18H13N5O4Se
442.29
18H13N3O4S
367.38
18H13N3O3S2
383.44
18H13N3O4Se
414.27
20H16N4O4S
408.43
20H16N4O3S2
C
4a
C
4b
C
169–170
EtOH
4c
8.11
8.01
15.59
15.48
—
C
134–137
Acetone
128–131
Acetone
134–137
Acetone
155–157
EtOH
151–155
EtOH
124–125
DMF/EtOH
164–166
EtOH
155–156
DMF/EtOH
152–154
Aq. EtOH
202–204
DMF/EtOH
207–209
DMF/EtOH
175–177
DMF/EtOH
213–214
DMF/EtOH
236–238
DMSO
187–189
DMF
170–173
DMF/EtOH
220–222
DMF
5a
C
5b
C
5c
8.73
8.70
16.72
16.66
—
C
7a
C
7b
C
7c
7.85
7.69
15.11
1501
—
C
8a
C
424.5
C20H16N4O4Se
455.33
8b
8c
6.62
6.55
12.81
12.69
—
C
26H20N4O4S
484.53
26H20N4O3S2
500.59
26H20N4O4Se
531.42
25H19N5O3S
469.52
26H19N5O5S
513.52
28H25N5O3S
511.59
26H21N5O3S
483.54
24H19N5O4S
9a
C
9b
C
9c
6.83
6.72
6.24
6.20
6.27
6.20
6.63
6.55
6.77
6.71
6.28
6.21
6.12
6.00
13.21
13.09
C
13a
13b
13c
13d
13e
13f
13g
14a
C
C
C
C
473.5
C26H18N6O4S
510.52
289–290
DMF/EtOH
234–236
DMF/EtOH
245–247
DMF/EtOH
Orange
78
Red
72
Orange
C
27H17N5O5S
523.52
25H19N5O2S2
485.58
C
(Continued on next page)

1868
E. K. A. ABDELALL ET AL.
Table I Characterization data of the newly synthesized compounds (Continued)
% Analyses, Calcd./Found
Mol. Formula
Mol. Wt.
Yielda%
Color
Mp, ◦C
Solvent
Compound
no.
S
N
H
C
12.11
12.00
12.15
12.01
12.84
12.90
13.10
13.01
12.18
12.09
11.89
11.79
—
13.22
13.09
13.27
13.09
14.02
14.21
14.31
14.19
15.96
16.02
12.98
12.78
12.74
12.69
11.49
11.33
11.80
11.77
12.38
12.49
11.19
11.30
11.49
11.36
14.42
14.53
12.66
12.73
12.22
12.00
3.62
3.69
4.78
4.71
4.24
4.05
3.91
3.82
3.45
3.33
3.18
3.01
4.95
4.79
5.13
5.23
4.58
4.66
4.81
4.78
4.99
4.89
4.46
4.33
3.94
3.81
4.10
4.00
3.96
3.82
58.97
58.89
63.73
63.66
62.50
62.41
58.88
58.69
59.30
59.49
60.10
60.00
67.75
67.69
65.02
64.92
64.75
64.96
65.82
65.69
63.35
63.46
63.04
63.22
61.85
61.79
65.14
65.01
62.86
62.89
C26H19N5O4S2
529.59
70
247–249
DMF
181–184
DMF
267–269
DMF
251–253
DMF
> 300
DMF/EtOH
241–243
DMF/EtOH
267–269
CHCl3/MeOH
244–246
CHCl3/MeOH
252–254
CHCl3/MeOH
260–263
CHCl3/MeOH
181–182
CHCl3/MeOH
267–269
14b
14c
14d
14e
14f
Pale orange
70
Pale orange
74
Orange
76
Yellow
78
Pale orange
80
Red
66
Yellow
64
Orange
60
Orange
61
Orange
62
Orange
66
Orange
78
Yellow
68
Yellow
65
Yellow
C
28H25N5O2S2
527.66
26H21N5O2S2
499.61
24H19N5O3S2
489.57
26H18N6O3S2
526.59
27H17N5O4S2
539.58
31H27N5O5
549.58
33H31N5O7
609.63
32H27N5O7
593.59
31H27N5O4S
565.64
33H31N5O6S
625.69
32H27N5O6S
609.65
25H19N5O4S
C
C
C
C
14g
20a
20b
20c
21a
21b
21c
26a
29a
29b
C
—
—
C
C
5.67
5.61
5.12
5.00
5.26
5.16
6.60
6.67
7.25
7.16
13.99
13.82
C
C
C
CHCl3/MeOH
251–253
EtOH
228–231
Acetic acid
221–223
C
485.51
C24H18N4O3S
442.49
C
24H18N4O2S2
458.56
Acetic acid
Synthesis of Ethyl 3-(4-(Benzoxazol-2-ylphenyl)-2-imino-1,3,4-
thiadiazoline-5-carboxylate (4a), Ethyl 3-(4-(Benzothiazol-2-ylphenyl)-
2-imino-1,3,4-thiadiazoline-5-carboxylate (4b), and Ethyl
3-(4-(Benzoxazol-2-ylphenyl)-2-imino-1,3,4-selenadiazoline-
5-carboxylate (4c)
Method A. A mixture of the appropriate 2a,b (0.005 mol) and the appropriate
amount of potassium thiocyanate (or potassium selenocyanate) (0.006 mol) in ethanol (25
mL) was stirred at room temperature for 24 h. The resulting solid was collected, washed
with water, and crystallized from ethanol to give 4a,b and 4c, respectively (Tables I and II).
Method B. A mixture of the appropriate 2a,b (0.005 mol) and thiourea (0.38 g,
0.005 mol) in ethanol (25 mL) was refluxed for 3 h. The solid product that formed after
cooling was collected and crystallized from ethanol to give products identical in all respects
(mp, mixed mp, and spectra) with 4a and 4b, respectively.

REACTIONS WITH HYDRAZONOYL HALIDES
1869
Table II 1H NMR spectroscopic data of some synthesized compounds
Spectral data
Compound
IR: 3258 (NH), 3055 (CH, aromatic), 2981 (CH, aliphatic), 1747 (CO), 1605 (C C), 1476
(CH2), 1363 (CH3)
2a
1H NMR: δ = 1.37 (t, 3H, J = 7.5 Hz, CH2CH3), 4.35 (q, 2H, J = 7.5 Hz, CH2CH3), 7.40 (d,
2H, J = 8Hz, ArH’s), 7.50 (d, 2H, J = 8Hz, ArH’s), 8.00 (d, 2H, J = 8Hz, ArH’s), 8.07 (d,
2H, J = 8Hz, ArH’s) and 10.89 (s, br., 1H, NH).
IR: 3132 (NH), 3055 (CH, aromatic), 2926 (CH, aliphatic), 1743 (CO), 1605 (C C), 1476
(CH2), 1355 (CH3)
2b
1H NMR: δ = 1.37 (t, 3H, J = 7.5 Hz, CH2CH3), 4.35 (q, 2H, J = 7.5 Hz, CH2CH3), 7.40 (d,
2H, J = 8Hz, ArH’s), 7.50 (d, 2H, J = 8Hz, ArH’s), 8.00 (d, 2H, J = 8Hz, ArH’s), 8.07 (d,
2H, J = 8Hz, ArH’s) and 10.89 (s, br., 1H, NH).
IR: 3462 (NH), 3057 (CH,aromatic), 2983 (CH, aliphatic), 1725 (CO, ester), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
4a
4b
4c
5a
5b
5c
7a
7b
7c
8a
8b
1H NMR: δ = 1.41(t, 3H, J = 7.5 Hz, CH2CH3), 4.35 (q, 2H, J = 7.5 Hz, CH2CH3), 7.36–8.36
(m, 9H, ArH’s and NH protons)
IR: 3460 (NH), 30.55 (CH,aromatic), 2981 (CH, aliphatic), 1729 (CO, ester), 1636 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.41(t, 3H, J = 7.5 Hz, CH2CH3), 4.34 (q, 2H, J = 7.5 Hz, CH2CH3), 7.36–8.36
(m, 9H, ArH’s and NH protons)
IR: 3463 (NH), 30.55 (CH,aromatic), 2981 (CH, aliphatic), 1725 (CO, ester), 1636 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.26 (t, 3H, J = 7.5 Hz, CH2CH3), 4.31 (q, 2H, J = 7.5 Hz, CH2CH3), 7.38–8.28
(m, 8H, ArH’s), 9.85 (s, br., 1H, NH, exchangable)
IR: 3055 (CH,aromatic), 2984 (CH, aliphatic), 1720 (CO, ester), 1636 (C N), 1550 (NO), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.41(t, 3H, J = 7.5 Hz, CH2CH3), 4.35 (q, 2H, J = 7.5 Hz, CH2CH3), 7.36–8.36
(m, 8H, ArH’s)
IR: 3055 (CH,aromatic), 2980 (CH, aliphatic), 1722 (CO, ester), 1636 (C N), 1603 (C C),
1535 (NO), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.41(t, 3H, J = 7.5 Hz, CH2CH3), 4.35 (q, 2H, J = 7.5 Hz, CH2CH3), 7.36–8.36
(m, 8H, ArH’s)
IR: 3057 (CH,aromatic), 2983 (CH, aliphatic), 1725 (CO, ester), 1628 (C N), 1603 (C C),
1537 (NO), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.35 (t, 3H, J = 7.5 Hz, CH2CH3), 4.38 (q, 2H, J = 7.5 Hz, CH2CH3), 7.39–8.36
(m, 8H, ArH’s)
IR: 3055 (CH,aromatic), 2981 (CH, aliphatic), 1725 (CO, ester), 1685 (CO), 1660 (CO,
conjugated), 1636 (C N), 1603 (C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.44 (t, 3H, J = 7.5 Hz, CH2CH3), 4.47 (q, 2H, J = 7.5 Hz, CH2CH3), 7.27–8.36
(m, 8H, ArH’s)
IR: 3055 (CH,aromatic), 2981 (CH, aliphatic), 1725 (CO, ester), 1683 (CO), 1636 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.44 (t, 3H, J = 7.5 Hz, CH2CH3), 4.47 (q, 2H, J = 7.5 Hz, CH2CH3), 7.27–8.38
(m, 8H, ArH’s)
IR: 3057 (CH,aromatic), 2983 (CH, aliphatic), 1725 (CO, ester), 1685 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.44 (t, 3H, J = 7.5 Hz, CH2CH3), 4.47 (q, 2H, J = 7.5 Hz, CH2CH3), 7.27–8.36
(m, 8H, ArH’s)
IR: 3057 (CH,aromatic), 2983 (CH, aliphatic), 1725 (CO, ester), 1685 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.45 (t, 3H, J = 7.5 Hz, CH2CH3), 2.41 (s, 3H, CH3CO N), 4.47 (q, 2H, J = 7.5
Hz, CH2CH3), 7.27–8.44 (m, 8H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1683 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.45 (t, 3H, J = 7.5 Hz, CH2CH3), 2.41 (s, 3H, CH3CO N), 4.47 (q, 2H, J = 7.5
Hz, CH2CH3), 7.27–8.44 (m, 8H, ArH’s)
(Continued on next page)

1870
E. K. A. ABDELALL ET AL.
Table II 1H NMR spectroscopic data of some synthesized compounds (Continued)
Spectral data
Compound
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1683 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
8c
1H NMR: δ = 1.45 (t, 3H, J = 7.5 Hz, CH2CH3), 2.32 (s, 3H, CH3CO N), 4.41 (q, 2H, J = 7.5
Hz, CH2CH3), 7.44–8.42 (m, 8H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1675 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
9a
9b
1H NMR: δ = 1.46 (t, 3H, J = 7.5 Hz, CH2CH3), 2.43 (s, 3H, 4-CH3C6H4), 4.53 (q, 2H, J = 7.5
Hz, CH2CH3), 7.26–8.50 (m, 12H, ArH’s)
IR: 3050 (CH,aromatic), 2981 (CH, aliphatic), 1725 (CO, ester), 1678 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.46 (t, 3H, J = 7.5 Hz, CH2CH3), 2.43 (s, 3H, 4-CH3C6H4), 4.53 (q, 2H, J = 7.5
Hz, CH2CH3), 7.26–8.50 (m, 12H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1674 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
9c
1H NMR: δ = 1.34 (t, 3H, J = 7.5 Hz, CH2CH3), 2.36 (s, 3H, 4-CH3C6H4), 4.41 (q, 2H, J = 7.5
Hz, CH2CH3), 7.32–8.48 (m, 12H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
13a
13b
13c
1H NMR: δ = 1.36 (t, 3H, J = 7.5 Hz, CH2CH3), 4.39 (q, 2H, J = 7.5 Hz, CH2CH3), 7.48–8.33
(m, 13H, ArH’s), 8.57 (s, 1H, CH
)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1466 (CH2), 1653 (CH3).
1H NMR: δ = 1.37 (t, 3H, J = 7.5 Hz, CH2CH3), 4.41 (q, 2H, J = 7.5 Hz, CH2CH3), 6.10 (s,
2H, OCH2O), 7.01–8.30 (m, 11H, ArH’s), 8.44 (s, 1H, CH
)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.28 (d, 6H, (CH3)2CH, 1.36 (t, 3H, J = 7.5 Hz, CH2CH3), 2.99 (sex, 1H,
(CH3)2CH, 4.39 (q, 2H, J = 7.5 Hz, CH2CH3), 7.23–8.35 (m, 12H, ArH’s), 8.46 (s, 1H, CH
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
)
13d
13e
1H NMR: insoluble
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.37 (t, 3H, J = 7.5 Hz, CH3CH2), 2.35 (s, 3H, CH3), 4.35 (q, 2H, J = 7.5 Hz,
CH2CH3), 6.35 (s, 1H, furan H-4), 7.48–8.38 (m, 10H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1680 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
13f
13g
14a
14b
14c
1H NMR: δ = 1.36 (t, 3H, CH3CH2, 4.42 (q, 2H, J = 7.5 Hz, CH2CH3), 6.85–8.38 (m, 12H,
ArH’s), 8.46 (s, br., 1H, NH)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1695 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.35 (t, 3H, J = 7.5 Hz, CH2CH3), 4.38 (q, 2H, J = 7.5 Hz, CH2CH3), 7.42–8.51
(m, 12H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.36 (t, 3H, J = 7.5 Hz, CH2CH3), 4.39 (q, 2H, J = 7.5 Hz, CH2CH3), 7.48–8.33
(m, 13H, ArH’s), 8.57 (s, 1H, CH
)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.35 (t, 3H, J = 7.5 Hz, CH2CH3), 4.41 (q, 2H, J = 7.5 Hz, CH2CH3), 6.10 (s,
2H, OCH2O), 6.98–8.23 (m, 11H, ArH’s), 8.42 (s, 1H, CH
)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.28 (d, 6H, (CH3)2CH), 1.36 (t, 3H, J = 7.5 Hz, CH2CH3), 2.99 (sex, 1H,
(CH3)2CH, 4.39 (q, 2H, J = 7.5 Hz, CH2CH3), 7.23–8.35 (m, 12H, ArH’s), 8.46 (s, 1H, CH
)

REACTIONS WITH HYDRAZONOYL HALIDES
1871
Table II 1H NMR spectroscopic data of some synthesized compounds (Continued)
Spectral data
Compound
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: insoluble
14d
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
14e
14f
14g
20a
1H NMR: δ = 1.37 (t, 3H, J = 7.5 Hz, (CH3CH2), 2.35 (s, 3H, CH3), 4.35 (q, 2H, J = 7.5 Hz,
CH2CH3), 6.35 (s, 1H, furan H-4), 7.48–8.38 (m, 10H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1682 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.36 (t, 3H, J = 7.5 Hz, CH3CH2), 4.42 (q, 2H, J = 7.5 Hz, CH2CH3), 6.85–8.38
(m, 12H, ArH’s), 8.46 (s, br., 1H, NH)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1690 (CO), 1628 (C N), 1603
(C C), 1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.30 (t, 3H, J = 7.5 Hz, CH3CH2), 4.29 (q, 2H, J = 7.5 Hz, CH2CH3), 7.48–8.48
(m, 12H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.23 (t, 3H, J = 7.5 Hz, CH3CH2), 1.42 (t, 3H, J = 7.5 Hz, CH3CH2), 2.88 (s, 3H,
CH3), 4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 4.45 (q, 2H, J = 7.5 Hz, CH2CH3), 6.67 (s, 1H,
pyrimidine H-4), 6.89–8.43 (m, 13H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
20b
20c
21a
21b
21c
1H NMR: δ = 1.23 (t, 3H, J = 7.5 Hz, CH3CH2), 1.42 (t, 3H, J = 7.5 Hz, CH3CH2), 2.88 (s, 3H,
CH3), 3.47 (s, 3H, OCH3), 3.72(s, 3H, OCH3), 4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 4.45 (q,
2H, J = 7.5 Hz, CH2CH3), 6.67 (s, 1H, pyrimidine H-4), 6.89–8.43 (m, 11H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.23 (t, 3H, J = 7.5 Hz, CH3CH2), 1.42 (t, 3H, J = 7.5 Hz, CH3CH2), 2.88 (s, 3H,
CH3), 4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 4.45 (q, 2H, J = 7.5 Hz, CH2CH3), 5.91 (s, 2H,
OCH2O), 6.67 (s, 1H, pyrimidine H-4), 6.89–8.43 (m, 11H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.23 (t, 3H, J = 7.5 Hz, CH3CH2), 1.42 (t, 3H, J = 7.5 Hz, CH3CH2), 2.88 (s, 3H,
CH3), 4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 4.45 (q, 2H, J = 7.5 Hz, CH2CH3), 6.67 (s, 1H,
pyrimidine H-4), 6.89–8.43 (m, 13H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.23 (t, 3H, J = 7.5 Hz, CH3CH2), 1.42 (t, 3H, J = 7.5 Hz, CH3CH2), 2.88 (s, 3H,
CH3), 3.47 (s, 3H, OCH3), 3.72(s, 3H, OCH3), 4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 4.45 (q,
2H, J = 7.5 Hz, CH2CH3), 6.67 (s, 1H, pyrimidine H-4), 6.89–8.43 (m, 11H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.23 (t, 3H, J = 7.5 Hz, CH3CH2), 1.42 (t, 3H, J = 7.5 Hz, CH3CH2), 2.88 (s, 3H,
CH3), 4.11 (q, 2H, J = 7.5 Hz, CH2CH3), 4.45 (q, 2H, J = 7.5 Hz, CH2CH3), 5.91 (s, 2H,
OCH2O), 6.67 (s, 1H, pyrimidine H-4), 6.89–8.43 (m, 11H, ArH’s)
IR: 3382 (NH), 3050 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1682 (CO), 1628
(C N), 1603 (C C), 1476 (CH2), 1663 (CH3).
26
1H NMR: δ = 1.39 (t, 3H, J = 7.5 Hz, CH3CH2), 4.42 (q, 2H, J = 7.5 Hz, CH2CH3), 7.42–8.35
(m, 13H, ArH’s), 11.42 (s, br., 1H, NH)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
29a
29b
1H NMR: δ = 1.39 (t, 3H, J = 7.5 Hz, CH3CH2), 4.42 (q, 2H, J = 7.5 Hz, CH2CH3), 7.06–8.38
(m, 13H, ArH’s)
IR: 3055 (CH,aromatic), 2983 (CH, aliphatic), 1728 (CO, ester), 1628 (C N), 1603 (C C),
1476 (CH2), 1663 (CH3).
1H NMR: δ = 1.39 (t, 3H, J = 7.5 Hz, CH3CH2), 4.44 (q, 2H, J = 7.5 Hz, CH2CH3), 7.08–8.23
(m, 13H, ArH’s)

1872
E. K. A. ABDELALL ET AL.
Synthesis of Ethyl 2-(Azanitrosomethylene)-3-(benzoxazol-2-ylphenyl)-
1,3,4-thiadiazoline-5-carboxylate (5a), Ethyl 2-(Azanitrosomethylene)-3-
(benzothiazol-2-ylphenyl)-1,3,4-thiadiazoline-5-carboxylate (5b), and Ethyl
2-(Azanitrosomethylene)-3-(benzoxazol-2-ylphenyl)-1,3,4-selenadiazoline-
5-arboxylate (5c)
A cold saturated solution of sodium nitrite (10 mL) was added dropwise to a solution
of the appropriate 4a–c (1 g) in acetic acid (20 mL) in an ice bath while stirring. The
reaction mixture was stirred for 30 min. The resulting solid was collected, washed with
water, and crystallized from acetone to give 5a–c, respectively (Tables I and II).
Synthesis of Ethyl 3-(4-Benzoxazol-2-ylphenyl)-
2-oxo-1,3,4-thiadiazoline-5-carboxylate (7a,) 3-(4-Benzothiazol-2-ylphenyl)-
2-oxo-1,3,4-thiadiazoline-5-carboxylate (7b), and Ethyl
3-(4-Benzoxazol-2-ylphenyl)-2-oxo-1,3,4-selenadiazoline-5-carboxylate (7c)
A solution of the appropriate 5a–c (0.5 g) in xylene (20 mL) was refluxed for 15 min.
Then the solvent was evaporated under reduced pressure. The residue oil was triturated
with petroleum ether (40–60◦C), and the solid formed was collected and crystallized from
the proper solvent to give 1,3,4-thiadiazolinone 7a,b and 1,3,4- selenadiazolinone 7c,
respectively (Tables I and II).
Acylation of 4a–c
Acetylation. A mixture of the appropriate 4a–c (1 g) in acetic acid (10 mL) and
acetic anhydride (5 mL) was warmed for 5 min at 70◦C. The reaction mixture was poured
onto ice water (40 mL). The solid was collected and crystallized to give the N-acetyl
derivatives 8a–c, respectively (Tables I and II).
Benzoylation. 4-Methybenzoyl chloride (1 mL) was added to a solution of the
appropriate 4a–c (0.5 g) in pyridine (15 mL), and the mixture was refluxed for 10 min, then
poured onto ice water (50 mL) and acidified with hydrochloric acid. The resulting product
was collected and washed several times with boiling water. The solid was recrystallized
from N,N-dimethylformamide to give the N-4-methylbenzoyl derivatives 9a–c, respectively
(Tables I and II).
Synthesis of Thiadiazolines 13a–g and 14a–g
Triethylamine (0.75 mL, 0.005 mol) was added dropwise with stirring to a mixture of
the appropriate alkyl carbodithioates 10a–g(a,b) or 101a–g(a,b) (0.005 mol) and compound
2 (1.8 g, 0.005 mol) in ethanol (20 mL). The resulting solid, which formed after 30
min, was collected and recrystallized from the proper solvent and gave the corresponding
thiadiazolines 13a–g and 14a–g, respectively, in a good yield (Tables I and II).
Synthesis of 1,2,4-Triazolo[4,3-a]pyrimidines 20a–c and 21a–c
Method A. A mixture of the appropriate hydrazonoyl chlorides 2a,b (0.005 mol)
and the appropriate 17a–c (1.9 g, 0.005 mol) in chloroform (20 mL) containing triethylamine
(0.75 mL, 0.005 mol) was refluxed for 10 h. Chloroform was evaporated under reduced

REACTIONS WITH HYDRAZONOYL HALIDES
1873
pressure, and the residue solid was recrystallized from chloroform/methanol mixture to
give 20a–c and 21a–c, respectively (Tables I and II).
Method B. Equimolar amounts of the appropriate hydrazonoyl chlorides 2a,b,
22a–c, and sodium ethoxide (0.005 mol each) in ethanol (20 mL) were refluxed for 3 h. The
reaction mixture was cooled, and the resulting solid was collected and recrystallized from
the proper solvent to give products identical in all respects (mp, mixed mp, and spectra)
with corresponding products obtained by method A.
Synthesis of Ethyl 4-(4-(Benzo[d]oxazol-2-yl)phenyl)-5-
(benzoylimino)-4,5-dihydro-1,3,4-thiadiazole-2-carboxylate (26)
Method A. Triethylamine (0.75 mL, 0.005 mol) was added dropwise with stirring
to a mixture of methyl benzoylcarbodithioate (24) (0.005 mol) and compound 2a (1.8
g, 0.005 mol) in ethanol (20 mL). The resulting solid, which formed after 30 min, was
collected and recrystallized from ethanol to give 26 (Tables I and II).
Method B. Triethylamine (0.75 mL, 0.005 mol) was added dropwise with stirring
to a mixture of 5-phenyl-1,3,4-oxadiazole-2-thiol (27) (0.005 mol) and compound 2a (1.8
g, 0.005 mol) in ethanol (20 mL). The resulting solid, which formed after 30 min, was
collected and recrystallized from ethanol to give 26 (Tables I and II).
Synthesis of Ethyl 4-(4-(Benzo[d]oxazol-2-yl)phenyl)-4,5-dihydro-5-
(phenylimino)-1,3,4-thiadiazole-2-carboxylate (29a) and Ethyl
4-(4-(Benzo[d]thiazol-2-yl)phenyl)-4,5-dihydro-5-(phenylimino)-
1,3,4-thiadiazole-2-carboxylate (29b)
Method A. Triethylamine (0.75 mL, 0.005 mol) was added dropwise with stirring to
a mixture of methyl phenylcarbamodithioate (28) (0.005 mol) and the appropriate amount
of hydrazonoyl chlorides 2a and 2b (1.8 g, 0.005 mol) in ethanol (20 mL) for 30 min.
The resulting solid was collected and recrystallized from acetic acid to give 29a and 29b,
respectively (Tables I and II).
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