Synthesis of 1,3,4-thiadiazines, bis-1,3,4-thiadiazoles, [1,2,4]triazino[3,4-b][1,3,4]thiadiazine, thiazolines from carbonothioic dihydrazide

Article abstract of DOI:10.1016/j.tet.2012.02.011

A novel and efficient synthesis of 1,3,4-thiadiazines, bis-1,3,4- thiadiazoles, [1,2,4]triazino[3,4-b][1,3,4]thiadiazine, and thiazolines is reported from the reaction of α-haloketo hydrazonoyl halides with carbonothioic dihydrazide or its analogues. The

Full text of DOI:10.1016/j.tet.2012.02.011

Tetrahedron 68 (2012) 2784e2789
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 1,3,4-thiadiazines, bis-1,3,4-thiadiazoles, [1,2,4]triazino[3,4-b][1,3,4]
thiadiazine, thiazolines from carbonothioic dihydrazide
,b,
Abdelwahed R. Sayed a
*
a Department of Chemistry, Faculty of Science, University of Beni Suef, Egypt
b Department of Chemistry, Faculty of Science, KFU, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel and efficient synthesis of 1,3,4-thiadiazines, bis-1,3,4-thiadiazoles, [1,2,4]triazino[3,4-b][1,3,4]
thiadiazine, and thiazolines is reported from the reaction of a-haloketo hydrazonoyl halides with car-
bonothioic dihydrazide or its analogues. The structures were elucidated on the basis of their elemental
analysis, spectral data and an alternative synthetic route.
Received 26 November 2011
Received in revised form 17 January 2012
Accepted 6 February 2012
Available online 10 February 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Hydrazonoyl halides
Carbonothioic dihydrazide
1,3,4-Thiadiazines
1,3,4-Thiadiazoles
[1,2,4]triazino[3,4-b][1,3,4]thiadiazine
Thiazolines
1. Introduction
2. Results and discussion
The most commonly used methods for the synthesis of 1,3,4-
thiadiazines are based on the transformations of compounds
whose structural fragments can be converted into the
SeC2eN3eN4 and C5eC6 moieties of the target thiadiazine ring.
The synthesis of thiadiazoles from the reaction of hydrazonoyl
halides not containing a -haloketone with carbonothioic dihy-
drazide has been previously reported.18 This work is continued by
a
treatment of carbonothioic dihydrazide19 2 with the
a-haloketo
Reactions of thiosemicarbazides with
wide application. Depending on the substituents in the
a
-halo ketones have found
-hal-
hydrazonoyl halide20 1 in DMF under heating and gave a single
a
isolated product in each case. These are similar to the reactions of
ocarbonyl fragment and in the thiosemicarbazide, as well as on
the reaction conditions, the products are thiadiazines,1e3 thia-
zoles,4,5 dihydrothiazoles,6,7 pyrazoles,3,8 or other heterocyclic
systems.7,8
1,3,4-Thiadiazines are efficient antibacterial and antifungal
compounds9 and their use in the treatment of the bacteria Heli-
cobacter pylori and as reverse transcriptase inhibitors of the human
immunodeficiency virus have been reported.10 1,3,4-Thiadiazoles
have been screened for their antibacterial and antifungal
activities,11e14 anti-inflammatory,15 anti-tuberculosis activity.16 It is
well-known that the thiazolyl group is of great importance in bi-
ological systems.17
thiosemicarbazides with a
-halo ketones1e7 and, for example, the
reaction of 1a with 2 in boiling DMF afforded product 3a via the
elimination of HCl and water. The IR spectrum of 3a revealed ab-
sorption bands at 3299, 3282, and 3240 cmꢀ1 due to the NH and
1
NH2 group. The H NMR spectrum showed signals at
d
2.26 (s, 3H,
5.38 (s, 2H, NH2 exchangeable with D2O)
7.11e7.38 (m, 4H, ArHs), [ 10.04 (s, 1H, NH), 10.54 (s, 1H,
CH3), 2.37 (s, 3H, CH3),
and at
d
d
d
d
NH) NH disappeared with D2O], Similarly, compounds 1bee reac-
ted with 2 to afford 1,3,4-thiadiazine 3bee as shown in Scheme 1.
Compound 3a reacted with benzaldehyde in DMF to give the
corresponding hydrazone 4a. The 1H NMR spectrum of 4a exhibited
resonances at
d
2.23 (s, 3H, CH3),
d
2.38 (s, 3H, CH3), and
d 7.14e8.36
Herein the synthesis of 1,3,4-thiadiazines, bis-1,3,4-thiadiazoles,
[1,2,4]triazino[3,4-b][1,3,4]thiadiazine, and thiazolines is reported.
(m, 10H, ArH, vinyl CH]), [
d
10.11 (s, 1H, NH), d
10.47 (s, 1H, NH) NH
disappeared with D2O]. Compound 4a was also obtained via the
reaction of 1a with 2-(phenylmethylene)carbonothioic dihy-
drazide21 5 in DMF/triethylamine and was identical in all respects
(mp, mixed mp, and spectra) with that obtained from 3a. Similarly,
* Corresponding author. E-mail address: arashad_2003@yahoo.com
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.011

A.R. Sayed / Tetrahedron 68 (2012) 2784e2789
2785
Scheme 1. Synthesis of 1,3,4-thiadiazine derivatives 3aee and 4aee.
reactions of 1bee with 5 afforded hydrazones 4bee as shown in
Scheme 1.
3. Antimicrobial activity
Also, the reaction of 2 with 1,4-[N,N0-diphenyl(bis-hydrazonoyl
The tested microorganism was Gram þve bacteria, Gram ꢀve
bacteria and some Fungal-plants. The sensitivity of the selected
microorganisms to some synthesized compounds were de-
termined in an in vitro culture that were dissolved in chloroform,
the tests were carried out using the filter paper and hole plate
method.27,28 Studies on the biological activity of compounds in
comparison with Ampicillin and tetracycline showed in Table 1.
In general all tested compounds were capable of a high inhibition
of the growth of Gram positive and Gram negative. Also, in the
Table 1 showed the tested compounds were a high inhibition
toward Candida albicans (Fungus) and negative Aspergillus flavus
(Fungus).
dichloride)]benzene22 6 in DMF gave bis-thiadiazole 7 as the only
product. The molecular formula of 7, C22H18N8S2, was consistent
with the elimination of 2HCl and 2NH2NH2. The structure of 7 was
elucidated by elemental analysis and spectroscopy. The IR spectrum
of 7 revealed absorption bands at 3295 and 3289 cmꢀ1 due to the
NH2 group. The 1H NMR spectrum showed signals at
NH2, exchangeable with D2O) and
d
5.95 (s, 2H,
d
7.23e8.25 (m, 14H, ArHs). Bis-
thiadiazole 7 reacted with benzaldehyde in DMF to give the cor-
responding bis-hydrazone 8, the structure of which was confirmed
by elemental analysis and spectral data. The 1H NMR spectrum of 8
exhibited a multiplet resonance at
d 7.38e8.56 (m, 26H, ArH, and
vinyl CH]) (Scheme 2). Compound 8 was also obtained via the
reaction of
6 with 2-(phenylmethylene)carbonothioic dihy-
4. Conclusion
drazide21 5 in DMF/triethylamine and was identical (mp, mixed mp,
and spectra) with that obtained from 7.
In summary, efficient syntheses and characterization of new
1,3,4-thiadiazines, bis-1,3,4-thiadiazoles, [1,2,4]triazino[3,4-b]
[1,3,4]thiadiazine, and thiazolines from carbonothioic dihydrazide
have been reported.
2-Hydrazono-3,5-diphenyl-2,3-dihydro-1,3,4-thiadiazole23
9
reacted with itself in DMF and triethylamine as catalyst via
nuclueophilic addition followed by elimination of hydrazine to give
a single isolated product 12 as shown in Scheme 3. Compound 12
was also obtained via the reaction of 1124 with bis-thiourea25 10 in
pyridine and was identical (mp, mixed mp, and spectra) with that
obtained from 9.
5. Experimental
5.1. General
Treatment of hydrazonoyl chlorides20 1a and 3a in CH3Cl/DMF
and triethylamine under heating gave the final product 13 via the
elimination of HCl and water. The IR spectrum of 13 revealed an
absorbtion band at 3311 (NH),1360 (CH3), 1593 (C]N). The 1H NMR
All melting points were determined on an electrothermal ap-
paratus and are uncorrected. IR spectra were recorded (KBr discs)
on a Shimadzu FT-IR 8201 PC spectrophotometer. 1H NMR spectra
were recorded in CDCl3 and (CD3)2SO solutions on a Varian Gemini
300 MHz spectrometer and chemical shifts are expressed in
of 13 exhibited a multiplet resonance at
d¼2.25 and 2.46 (s, 6H,
2CH3), 7.09e7.95 (m, 8H, ArHs), 10.02 (br, 2H, 2NH) ppm as shown
in Scheme 4.
Treatment of carbonothioic dihydrazone26 14 with the appro-
priate hydrazonoyl halide20 1 in DMF under heating gave a single
isolated product in each case. For example, the reaction of 1a with
14 in boiling DMF afforded product 3a via the elimination of HCl
and water (Scheme 5).
d units using TMS as an internal reference. Mass spectra were
recorded on a GCeMS QP 1000 EX Shimadzu. The prepared
compounds were subjected to CHN elemental analyses using 2400
elemental analyzed at the Microanalytical center of the Cairo
University.

2786
A.R. Sayed / Tetrahedron 68 (2012) 2784e2789
Scheme 2. Synthesis of bis(1,3,4-thiadiazole)derivatives 7 and 8.
Scheme 3. Synthesis of bis(1,3,4-thiadiazole) 12.
5.2. Hydrazines 3aee and 7
benzene 6 (1.91 g, 5 mmol) with carbonothioic dihydrazide 2
(0.53 g, 5 mmol) in DMF (50 mL) were refluxed for 12 h. The
resulting solids were collected and recrystallized from an appro-
priate solvent to give yellow brown crystals 3aee and 7.
An equimolar amount of the appropriate hydrazonoyl halides
1aee (5 mmol) or 4-[N,N0-diphenyl(bis-hydrazonoyl dichloride)]

A.R. Sayed / Tetrahedron 68 (2012) 2784e2789
2787
Scheme 4. Synthesis of [1,2,4]triazino[3,4-b][1,3,4]thiadiazine 13.
Scheme 5. Synthesis of thiazoline derivatives 15.
Table 1
Response of various microorganisms to some synthesized compounds in vitro (culture)
Sample
Inhibition zone diameter (mm/mg sample)
Escherichia coli (Gꢀ
)
Staphylococcus albus (Gþ)
Aspergillus flavus (Fungus)
Candida albicans (Fungus)
Control: DMSO
Standard
0.0
33
0.0
12
17
0.0
0.0
0.0
30
0.0
13
19
0.0
0.0
0.0
0.0
19
0.0
0.0
0.0
0.0
0.0
0.0
20
12
14
0.0
0.0
Tetracycline antibacterial agent
Amphotericin B antifungal agent
3a
3d
4a
13
St. Reference standard; Chloramphenicol was used as a standard antibacterial agent; Terbinafin was used as a standard antifungal agent. Values show zone of inhibition in mm.
Diameter of the inhibition zones were: high (above 11 mm), negative (0).
5.2.1. [6-(4-Tolylhydrazo)-5-methyl-6H-1,3,4-thiadiazin-2-yl]hydra-
CH3); 5.38 (s, 2H, NH2), 7.11e7.38 (m, 4H, phenyl protons),10.04 (s,
1H, NH), 10.54 (s, 1H, NH) ppm; m/z (%)¼262 (37). Anal. Calcd for
C11H14N6S: C, 50.36; H, 5.38; N, 32.04. Found: C, 50.29; H, 5.33; N,
32.11%.
zine (3a). Yellow brown from EtOH/DMF, Yield (80%); mp 240 ꢁC;
IR: 399, 3282, 3240 (NH and NH2), 1606 (C]N), 1362 (CH3) cmꢀ1
;
1H NMR (dimethyl sulfoxide-d6):
d
¼2.26 (s, 3H, CH3); 2.37 (s, 3H,

2788
A.R. Sayed / Tetrahedron 68 (2012) 2784e2789
5.2.2. [6-(Phenylhydrazo)-5-methyl-6H-1,3,4-thiadiazin-2-yl]hydꢁra-
(s, 1H, NH), 10.47 (s, 1H, NH) ppm; m/z (%)¼350 (12). Anal. Calcd for
18H18N6S: C, 61.69; H, 5.18; N, 23.98. Found: C, 61.61; H, 5.23; N,
23.92%.
zine (3b). Yellow brown from EtOH/DMF, Yield (77%); mp 235 C;
C
IR: 3389, 3325, 3212 (NH and NH2), 1597 (C]N), 1434 (CH3) cmꢀ1
;
1H NMR (dimethyl sulfoxide-d6):
NH2), 6.90e7.26 (m, 5H, phenyl protons), 10.11(s, 1H, NH), 10.63 (s,
1H, NH) ppm; 13C NMR (dimethyl sulfoxide-d6):
d
¼2.25 (s, 3H, CH3); 5.31(s, 2H,
5.3.2. N-Benzylidene-N0-(6-phenylhydrazono-5-methyl-6H-[1,3,4]
d
¼15.12, 114.82,
thiadiazine-2-yl)-hydrazine (4b). Brown from EtOH/DMF, Yield
122.25, 124.30, 130.02, 144.81, 176.98; 177.02; m/z (%)¼248 (15).
Anal. Calcd for C10H12N6S: C, 48.37; H, 4.87; N, 33.85. Found: C,
48.35; H, 4.83; N, 33.89%.
(67%); mp 190ꢁC; IR: 3258, 3163(NH),1608 (C]N); 1368 (CH3) cmꢀ1
;
1H NMR (dimethyl sulfoxide-d6):
10H, phenyl protons), 8.37 (s,1H, ]CH),10.15 (s,1H, NH),10.63 (s,1H,
NH) ppm; m/z (%)¼336 (22). Anal. Calcd for C17H16N6S: C, 60.69; H,
4.79; N, 24.98. Found: C, 60.45; H, 4.77; N, 24.88%.
d
¼2.39 (s, 3H, CH3), 6.89e7.56 (m,
5.2.3. [6-(4-Chloro-phenylhydrazo)-5-methyl-6H-1,3,4-thiadiazin-2-
yl]hydrazine (3c). Yellow brown from EtOH/DMF, Yield (84%); mp
238 ꢁC; IR: 3290, 3275, 3229 (NH and NH2), 11,593 (C]N), 1362
5.3.3. N-Benzylidene-N0-(6-p-chlorophenylhydrazono-5-methyl-6H-
[1,3,4]thiadiazine-2-yl)-hydrazine (4c). Brown from EtOH/DMF,
Yield (87%); mp 195 ꢁC; IR: 3259, 3165 (NH), 1597 (C]N); 1371
(CH3) cmꢀ1
;
1H NMR (dimethyl sulfoxide-d6):
d
¼2.39 (s, 3H, CH3);
5.34 (s, 2H, NH2), 7.15e7.51 (m, 4H, phenyl protons), 10.11(s, 1H,
NH), 10.89 (s, 1H, NH) ppm; m/z (%)¼282 (40). Anal. Calcd for
C10H11ClN6S: C, 42.48; H, 3.92; N, 29.72. Found: C, 42.55; H, 3.99; N,
29.67%.
(CH3) cmꢀ1
;
1H NMR (dimethyl sulfoxide-d6):
d
2.34¼(s, 3H, CH3),
(m, 9H, phenyl protons), 8.54 (s,1H, ]CH), 9.99 (s,1H, NH),11. 54 (s,
1H, NH) ppm; m/z (%)¼370 (15). Anal. Calcd for C17H15ClN6S: C,
55.06; H, 4.08; N, 22.66. Found: C, 55.12; H, 3.98; N, 22.59%.
5.2.4. [6-(3-Chloro-phenylhydrazo)-5-methyl-6H-1,3,4-thiadiazin-2-
yl]hydrazine (3d). Yellow brown from EtOH/DMF, Yield (76%); mp
243 ꢁC; IR: 3298, 3268, 3153 (NH and NH2), 1595 (C]N), 1362 (CH3)
5.3.4. N-Benzylidene-N0-(6-m-chlorophenylhydrazono-5-methyl-6H-
[1,3,4]thiadiazine-2-yl)-hydrazine (4d). Brown from EtOH/DMF,
Yield (87%); mp 185 ꢁC; IR: 3261, 3164 (NH), 1618 (C]N), 1347 (CH3)
cmꢀ1; 1H NMR (dimethyl sulfoxide-d6):
d
¼2.34 (s, 3H, CH3); 5.28 (s,
2H, NH2), 7.07e7.44 (m, 4H, phenyl protons),10.08 (s,1H, NH),10.81
(s, 1H, NH) ppm; m/z (%)¼282 (36). Anal. Calcd for C10H11ClN6S: C,
42.48; H 3.92; N, 29.72. Found: C, 42.51; H, 4.03; N, 29.75%.
cmꢀ1
;
1H NMR (dimethyl sulfoxide-d6):
d¼2.49 (s, 3H, CH3),
7.24e8.06 (m, 9H, phenyl protons), 8.48 (1,1H, ]CH), 9.96 (s,1H, NH),
11.65 (s,1H, NH) ppm; m/z (%)¼370 (10). Anal. Calcd for C17H15ClN6S:
C, 55.06; H, 4.08; N, 22.66. Found: C, 55.09; H, 4.11; N, 22.71%.
5.2.5. [6-(3-Nitro-phenylhydrazo)-5-methyl-6H-1,3,4-thiadiazin-2-
yl]hydrazine (3e). Yellow brown from EtOH/DMF, Yield (79%); mp
245 ꢁC; IR: 3296, 3269, 3234 (NH and NH2),1603 (C]N),1369 (CH3)
5.3.5. N-Benzylidene-N0-(6-m-nitrophenylhydrazono-5-methyl-6H-
[1,3,4]thiadiazine-2-yl)-hydrazine (4e). Brown from EtOH/DMF,
Yield (76%); mp 219 ꢁC; IR: 3261, 3171 (NH), 1618 (C]N),1347 (CH3)
cmꢀ1; 1H NMR (dimethyl sulfoxide-d6):
d
¼2.37 (s, 3H, CH3); 5.38 (s,
2H, NH2), 7.17e7.64 (m, 4H, phenyl protons), 10.11 (s, 1H, NH), 10.89
(s, 1H, NH) ppm; m/z (%)¼293 (3). Anal. Calcd for C10H11N7O2S: C,
40.95; H, 3.78; N, 33.43. Found: C, 40.89; H, 3.69; N, 33.51%.
cmꢀ1
;
1H NMR (dimethyl sulfoxide-d6):
d
¼2.43 (s, 3H, CH3),
7.46e7.81 (m, 9H, phenyl protons), 8.53 (s, 1H, ]CH), 10.23 (s, 1H,
NH), 11.69 (s, 1H, NH) ppm; m/z (%)¼381 (37). Anal. Calcd For
C17H15N7O2S: C, 53.53; H, 3.96; N, 25.71. Found: C, 53.67; H, 4.02; N,
25.68%.
5.2.6. 1,4-Bis-(3-phenyl-3H[1,3,4]thiadiazol-2-hydrazino)
(7). Yellow brown from EtOH/DMF, Yield (64%); mp >300 ꢁC; IR:
3295, 3289 (NH2), 1635 (C]C, ArH), 1598 (C]N) cmꢀ1 1H NMR
(dimethyl sulfoxide-d6):
¼5.95 (s, 4H, 2NH2), 7.23e8.25 (m, 14H,
phenyl protons) ppm, 13C NMR:
benzene
;
5.3.6. 1,4-Bis-(3-phenyl-3H[1,3,4]thiadiazol-2-hydrazono)benzene
d
(8). Brown from EtOH/DMF, Yield (60%); mp >300 ꢁC; IR: 1590 (C]
d
¼122.96, 127.15, 130.19, 131.97,
N); 1H NMR (dimethyl sulfoxide-d6):
protons and vinyl CH¼) ppm; m/z (%)¼382 (100). Anal. Calcd. for
C36H26N8S2: C, 68.12; H, 4.13; N, 17.65. Found: C, 68.31; H, 4.09; N,
17.85%.
d
¼7.38e8.56 (m, 26H, phenyl
134.12, 139.67, 147.67, and 156.58 ppm; m/z (%)¼382 (100). Anal.
Calcd. for C22H18N8S2: C, 57.62; H, 3.96; N, 24.44. Found: C, 57.69; H,
3.88; N, 24.51%.
5.3. Hydrazones 4 and bis-hydrazone (8)
5.3.7. N,N0-Bis-(3,5-diphenyl-3H-[1,3,4]thiadiazol-2-ylidene)-hydra-
zine (12). Method A. The appropriate 1,3,4-thiadiazole derivative 9
(1.34 g, 5 mmol) was dissolved in DMF (30 mL) containing trie-
thylamine (0.502 g, 5 mmol) as catalyst and then refluxed for 6 h.
The resulting solids were collected by cooling and crystallized from
ethanol/DMF to give 12.
Method B. An equimolar amount of the appropriate hydrazonoyl
bromide 11 (1.375 g, 5 mmol), bis-thiourea 10 (0.075 g, 5 mmol
each) in pyridine (20 mL) were refluxed for 3 h. The excess solvent
was distilled until dryness and the residue was triturated with
a few drops of methanol or petroleum ether (40e60 ꢁC) where it
solidified. The solid product was filtered and crystallized from
ethanol/DMF to give final product (12). Yellow brown from EtOH/
DMF, Yield (91%); mp 275 ꢁC(Lit mp. 273); IR: 1573 (C]N) cmꢀ1; 1H
Method A. An equimolar amount of the appropriate hydrazonoyl
halides 1aee (5 mmol) or diphenyl(bis-hydrazonoyl dichloride)]
benzene 6 (1.91 g, 5 mmol) and 2-(phenylmethylene)-carbon-
othioic dihydrazide 5 (0.97 g, 5 mmol each) in DMF (40 mL), and
triethylamine (0.51 g, 5 mmol) were refluxed for 6 h at boiling
point. The resulting solids were collected during hot by filtration
and crystallized from an appropriate solvent to give 4 and 8.
Method B. An equimolar amount of the appropriate 1,3,4-
thiadiazine derivatives 3aee (5 mmol) or 1,4-bis-(3-phenyl-3H
[1,3,4]thiadiazol-2-hydrazino). Benzene 7 (2.29 g, 5 mmol) and
benzaldehyde (0.53 g, 5 mmol) in DMF (30 mL) containing two
drops of HCl as catalyst and then refluxed for 6 h. The resulting
solids were collected by cooling and crystallized from an appro-
priate solvent to give 4 and 8.
NMR (dimethyl sulfoxide-d6):
d
¼7.47e8.08 (m, 20H, phenyl pro-
tons) ppm; m/z (%)¼504 (35). Anal. Calcd For C28H20N6S2: C, 66.64;
H, 3.99; N, 16.65. Found: C, 66.58; H 4.05,; N, 16.60%.
5.3.1. N-Benzylidene-N0-(6-p-tolylhydrazono-5-methyl-6H-[1,3,4]
thiadiazine-2-yl)-hydrazine (4a). Brown from EtOH/DMF, Yield
(87%); mp 178 ꢁC; IR: 3277, 3145 (NH), 1612 (C]N) 1355 (CH3)
5.3.8. 4,8-Di(tolylhydrazo)-3,7-dimethyl-[1,2,4]triazino[3,4-b][1,3,4]
thiadiazine (13). To
a solution of hydrazonoyl chlorides 1a
cmꢀ1; 1H NMR (dimethyl sulfoxide-d6):
3H, CH3), 7.14e7.35 (m, 9H, phenyl protons), 8.36 (s,1H, ]CH),10.11
d
¼2.23 (s, 3H, CH3); 2.38 (s,
(0.005 mol) and 3a (0.005 mol) in chloroform (40 mL) and DMF
(10 mL), was added triethylamine (0.7 mL, 0.007 mol). The resulting

A.R. Sayed / Tetrahedron 68 (2012) 2784e2789
2789
mixture was refluxed for 16 h, and then cooled. The excess solvent
References and notes
was distilled until dryness and the residue was triturated with
a few drops of methanol or petroleum ether (40e60 ꢁC) where it
solidified. The solid product was filtered and crystallized from
ethanol/DMF to give final product (13). Red brown from EtOH/DMF,
Yield (64%); mp 220 ꢁC; IR: 3311 (NH), 1360 (CH3), 1593 (C]N)
1. Bose, P. K.; Nandi, B. K. J. Indian Chem. Soc. 1930, 733; Chem. Abstr. 1931, 25, 1532.
2. Campaigne, E.; Selby, T. P. J. Heterocycl. Chem. 1978, 15, 401.
3. Mamedov, V. A.; Krokhina, L. V.; Berdnikov, E. A.; Levin, Y. A. Khim. Geterotsikl.
Soedin. 1996, 1266.
4. Postovskii, I. Y.; Novikova, A. P.; Chechulina, L. A.; Sidorova, L. P. Khim. Geter-
otsikl. Soedin. 1976, 1051.
5. Mamedov, V. A.; Berdnikov, E. A.; Valeeva, V. N.; Ismaev, I. E.; Rizvanov, I. K. h.;
Antokhina, L. A.; Nuretdinov, I. A.; Chernov, P. P. Izv. Akad. Nauk, Ser. Khim. 1993,
1962.
cmꢀ1
;
1H NMR (dimethyl sulfoxide-d6):
d¼2.25 (s, 6H, 2CH3); 2.46
(s, 6H, 2CH3); 7.09e7.95 (m, 8H, phenyl protons); 10.02 (br, 2H,
2NH) ppm; m/z (%)¼418 (7). Anal. Calcd for C21H22N8S: C, 60.27; H,
5.30; N, 26.77. Found: C, 60.32; H, 5.23; N, 26.80%.
6. Beyer, H. Z. Chem. 1969, 9, 361.
7. Usol’tseva, S. V.; Andronnikova, G. P.; Mokrushin, V. S. Khim. Geterotsikl. Soedin.
1991, 435.
8. Beyer, H.; Honenck, H.; Reichelt, L. Justus Liebigs Ann. Chem. 1970, 741, 45.
9. Costin, J. C. U.S. Patent 6,555,534, 2003.
5.4. Thiazoline (15)
10. Witvrouw, M; Arranz, M. E.; Pannecouque, C.; Declercq, R.; Jonckheere, H.;
Schmit, J.-C.; Vandamme, A.-M.; Diaz, J. A.; Ingate, S. T.; Desmyter, J.; Esnouf, R.;
Van Meervelt, L.; Vega, S.; Balzarini, J.; De Clercq, E. Antimicrob. Agents Che-
mother. 1998, 42, 618.
11. Hussain, S.; Sharma, J.; Amir, M. E-J. Chem. 2008, 5, 963.
12. Qandil, A. M.; Tumah, H. N.; Hassan, M. A. Acta Pharm. Sci. 2006, 48, 95.
13. Dogan, H. N.; Rollas, S.; Erdeniz, H. IL Farmaco 1998, 53, 462.
14. Dogan, H. N.; Duran, A.; Rollas, S.; Sener, G.; Uysal, M. K.; Gulen, D. Bioorg. Med.
Chem. 2002, 10, 2893.
An equimolar amount of the appropriate hydrazonoyl chlorides
1a,c (5 mmol), bis-hydrazone 14 in DMF (40 mL) were refluxed for
12 h. The resulting solids were collected and recrystallized from an
appropriate solvent to give yellow brown crystals.
5.4.1. Benzylidene-[2-(benzildene-azo)-4-methyl-5-p-tolylazo-thia-
zol-3-yl]-amine (15a). Brown from EtOH/DMF, Yield (82%); mp
200 ꢁC; IR: 3054 (CH]aromatic) 1600 (C]C); 1353, 1312 (2 CH3);
15. Palaska, E.; Sahin, G.; Kelicen, P.; Turlu, N. T.; Altinok, G. IL Farmaco 2002, 57,
101.
16. Karakus, S.; Rollas, S. IL Farmaco 2002, 57, 577.
1H NMR (dimethyl sulfoxide-d6):
7.01e8.34 (m, 16H, phenyl protons and 2¼CH) ppm; m/z (%)¼438
(32). Anal. Calcd for C25H22NS: C, 68.47; H, 5.06; N, 19.16. Found: C,
68.51; H, 5.12; N, 19.13%.
d
¼2.08 and 2.25 (s, 6H, 2CH3),
17. Srivastava, P. N.; Rai, S. K. Eur. J. Med. Chem. Chim. Ther. 1980, 15, 274.
1
8. Sayed, A. R. Tetrahedron Lett. 2010, 51, 4490.
19. Autenrieth, W.; Hefner, H. Ber. Dtsch. Chem. Ges. 1925, 58B, 2151.
20. Shawali, A. S.; Mosselhi, M. A. N.; Tawfik, N. M. J. Org. Chem. 2001, 66, 4055.
21. Kabashima, S.; Okawara, T.; Yamasaki, T.; Furukawa, M. Heterocycles 1990, 31,
1129.
22. Stille, J. K.; Harris, F. W. J. Polym. Sci., Part A: Polym. Chem. 1968, 6, 2317.
23. Hussein, A. E.; Hussein, F. Z.; Abdelhamid, A. O. J. Chem. Res., Synop. 1998, 12; J.
Chem. Res., Miniprint 1998, 0169.
24. Shawali, A. S.; Abdallah, M. A.; Zayed, M. M. J. Heterocycl. Chem. 2002, 39, 45.
25. Fusco, R. R. Ist. Lomb. Sci. 1938, 71, 425.
26. Badawy, M. A.; Abdel-Hady, S. A.; Ibrahim, Y. A. Liebigs Ann. Chem. 1990, 393.
27. Solomons, W. E.; Doorenbos, N. J. J. Pharm. Sci. 1974, 63, 19.
28. Lefert, C. R.; Siripumchidbouree, H.; Hamspons, S.; Workman, S.; Sigee, D.;
Epton, HA. S.; Harbour, A. J. Appl. Bacteriol. 1955, 78, 97.
5.4.2. Benzylidene-[2-(benzildene-azo)-4-methyl-5-p-chlropheny-
lazo-thiazol-3-yl]-amine (15c). Brown from EtOH/DMF, Yield (82%);
mp 170 ꢁC; IR: 3027 (CH]aromatic) 1610 (C]C); 1346 (CH3); 1H
NMR (dimethyl sulfoxide-d6):
d¼2.34 (s, 3H, 1CH3), 7.11e8.36 (m,
16H, phenyl protons and 2]CH) ppm; m/z (%)¼458 (18). Anal.
Calcd for C24H19ClN6S: C, 62.81; H, 4.17; N, 18.31. Found: C, 62.79; H,
4.21; N, 18.39%.