Synthesis of bis-thiazoles, bis-pyrazoles, bis-hydrazonates, and bis-triazolothiadiazoles based on bis-hydrazonoyl and bis-hydrazones

Article abstract of DOI:10.3906/kim-1412-77

A facile synthesis of bis-thiazoles, bis-pyrazoles, and bis-hydrazonates from the reaction of bis-hydrazonoyl dichlorides with different moieties is described. Bis-triazolothiadiazoles were synthesized via oxidative cyclization of bis-hydrazones. Structures of the final product were elucidated by elemental analyses and spectral data.

Full text of DOI:10.3906/kim-1412-77

Turk J Chem
Turkish Journal of Chemistry
(2015) 39: 600 – 609
¨
http://journals.tubitak.gov.tr/chem/
˙
c
⃝ TUBITAK
doi:10.3906/kim-1412-77
Research Article
Synthesis of bis-thiazoles, bis-pyrazoles, bis-hydrazonates, and
bis-triazolothiadiazoles based on bis-hydrazonoyl and bis-hydrazones
Abdelwahed SAYED1,2,∗
1Department of Chemistry, Faculty of Science, KFU, Hofuf, Saudi Arabia
2Department of Chemistry, Faculty of Science, University of Beni Suef, Egypt
Received: 31.12.2014
•
Accepted/Published Online: 22.03.2015
•
Printed: 30.06.2015
Abstract: A facile synthesis of bis-thiazoles, bis-pyrazoles, and bis-hydrazonates from the reaction of bis-hydrazonoyl
dichlorides with different moieties is described. Bis-triazolothiadiazoles were synthesized via oxidative cyclization of
bis-hydrazones. Structures of the final product were elucidated by elemental analyses and spectral data.
Key words: Bis-hydrazonoyl, bis-thiazoles, bis-pyrazoles, bis-hydrazonates, bis-hydrazones
1. Introduction
The interest in the chemistry of hydrazonoyl halides is a consequence of the fact that they undergo a wide vari-
ety of reactions.1,2 Thiazole compounds can be prepared from hydrazonoyl halides, which act as antibacterial,3
antifungal,4 anti-inflammatory,5 and anthelmintic agents.6 In addition, hydrazonoyl halides are useful precur-
sors of nitrilimines, which can undergo 1,3-dipolar cycloaddition reactions used for both academic and industrial
purposes.7 Moreover, hydrazonoyl halides can be used to prepare pyrazoles with a broad spectrum of important
biological and pharmaceutical activities such as antimicrobial, antihypertensive, antitumor, anti-inflammatory,
antidepressant, and anticonvulsant activities.8−9 In addition, hydrazonoyl halides have proved to be useful
synthons for various hydrazonate and thiohydrazonate esters.10
Efficient syntheses of new bis-thiazoles, bis-pyrazoles, bis-hydrazonates, and triazolothiadiazoles are
reported.
2. Results and discussion
Bis-hydrazonoyl chlorides are highly versatile reagents and useful building blocks for the synthesis of bis-
heterocyclic rings.11 The target compounds 8–17 were synthesized in two steps. In the first step, the thiosemi-
carbazones 3–712 were prepared by condensing equimolar amounts of substituted aldehyde with thiosemicar-
bazide. In the second step, reaction of bis-hydrazonoyl chlorides 1 and 213 with thiosemicarbazone 3–7 in
dioxane in the presence of triethylamine under heating afforded in each case only one product, as examined by
TLC. The reaction provided the desired products in excellent yields. The final products were established by
elemental analyses and spectroscopic data. The mass spectra of the products revealed in each case a molecular
ion peak in agreement with the molecular formula for each compound. The IR spectra showed the absence of
the C=O absorption bands present in the starting bis-hydrazonoyl chlorides 1 and 2 as depicted in Schemes 1
and 2.
∗Correspondence: arsayed@kfu.edu.sa
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Scheme 1. Synthesis of bis-thiazole derivatives 8–12.
1,3-Dipolar cycloadditions reactions are important and versatile for constructing five-membered rings
including pyrazoles.11,14 Reaction of bis-hydrazonoyl chlorides 1 and 2 with dimethyl acetylenedicarboxylate
19 in dioxane and in the presence of triethylamine each gave one isolated product, 20 and 22, respectively
(Schemes 3 and 4). In the presence of base bis-hydrazonoyl chlorides 1 and 2 convert into bis-nitrilimines 18 or
21, respectively. This undergoes cycloadditions with dipolarophiles such as dimethyl acetylenedicarboxylate 19
to give pyrazoles. The isolated final products 20 and 22 gave satisfactory elemental analyses and spectroscopic
data (IR, NMR, and MS) consistent with their assigned structures. The IR spectra of the products 20 and 22
showed no NH absorption band.
Previously, the synthesis of arylhydrazonates by reaction of phenols with hydrazonoyl halides was
reported.15 Treatment of bis-hydrazonoyl dichlorides 1 and 2 with 4-bromophenol 23 in NaOMe at room
temperature gave the final products 24 and 25, respectively (Scheme 5). 13 C NMR spectra for 25 could not
be recorded owing to the poor solubility of the products in the available NMR solvents.
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Scheme 2. Synthesis of bis-thiazole derivatives 13–17.
Reaction of bis-hydrazones 27a–c with two equivalent amounts of ferric chloride in ethanol for 30 min gave
crystalline products 29a–c. The compounds 29a–c were elucidated by elemental analyses and spectral data.
Elemental analyses and mass spectra revealed that the isolated products had four hydrogens fewer than the
respective bis-hydrazones 27a–c.16 The 1 H NMR spectra showed the absence of both methine (–N=CH–) and
hydrazone (–NHN=C) protons. Formation of the final products 29a–c was suggested to proceed by oxidative
cyclizations via the formation of the respective bis-nitrilimine 28, which underwent in situ 1,5-electrocyclization
to give 29a–c as depicted in Scheme 6.
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Scheme 3. Synthesis of bis-pyrazole 20.
Scheme 4. Synthesis of bis-pyrazole 22.
3. Experimental section
All the chemicals were purchased from Aldrich and Fluka and used without further purification. Melting points
were measured on an electrothermal Gallenkamp melting point apparatus and are uncorrected. The 1 H and
13 C NMR spectra were recorded in DMSO-d6 with tetramethylsilane (TMS) as an internal standard using a
300 MHz Varian Gemini spectrometer. The IR spectra were measured on Fourier Transform and Pye Unicam
Infrared spectrophotometers using potassium bromide wafers. Mass spectra were recorded on a GCMS-QP
1000 EX spectrometer at an ionizing potential of 70 eV. Elemental microanalyses were carried out at the
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Scheme 5. Synthesis of thiohydrazonate derivatives 24 and 25.
Scheme 6. Synthesis of bis-triazolo[3,4-b]thiadiazole derivatives 29a–c.
Microanalytical Laboratory of Cairo University, Giza, Egypt. The identification of compounds from different
experiments was secured by mixed mp and superimposable IR spectra.
3.1. General procedure for the synthesis of 8–17
A mixture of the appropriate bis-hydrazonoyl chlorides 1 or 2 (5 mmol), the appropriate thiosemicarbazone
derivatives 3–7 (10 mmol), and triethylamine (1 g, 1.5 mL, 10 mmol) in dioxane (20 mL) was heated under
reflux for 3 h and then left to cool. The solid precipitated was collected, washed with water, dried, and finally
crystallized from DMF/MeOH to give the final products 8–17.
3.1.1. 5,5′ -(4,4′ -Diphenylsulphone-4,4′ -diyl)-bis-((2-(p-methylbenzylidenehydrazino)-4-methyl-5-
azo-1,3-thiazole) (8a)
Brown solid; Yield (89%); mp: 252 ◦ C. IR (KBr): νmax 3219 (NH) cm−1
.
1 H NMR (DMSO-d6): 2.38 (s,
6H, 2CH3), 2.57 (s, 6H, 2CH3), 7.39–7.88 (m, 16H, ArH), 8.67 (s, 2H, N=CH), and 10.96 (s, 2H, NH), 13 C
NMR (DMSO-d6): at 16.82, 21.62, 115.20, 129.45, 130.01, 130.45, 132.42, 136.2, 140.06, 141.91, 142.02, 143.18,
160.12, and 171.82 ppm. MS m/z (%): 732 (M+ , 42). Analysis Calcd for C36 H32 N10 O2 S2 (732.19): C, 59.00;
H, 4.40; N, 19.11; Found: C, 59.03; H, 4.39; N, 19.14%.
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3.1.2. 5,5′ -(4,4′ -Diphenylsulphone-4,4′ -diyl)-bis-((2-(benzylidenehydrazino)-4-methyl-5-azo-1,3-
thiazole) (8b)
Red solid; Yield (89%); mp: 250 ◦ C. IR (KBr): νmax 3222 (NH), 1595 (C=C) cm−1 1 H NMR (DMSO-d6):
.
2.56 (s, 6H, 2CH3), 7.45–7.86 (m, 18H, ArH), 8.65 (s, 2H, N=CH), and 10.97 (s, 2H, NH), 13 C NMR (DMSO-
d6): at 16.59, 114.42, 128.42, 128.91, 128.99, 131.75, 133.70, 134.41, 140.90, 147.39, 160.82, 172.66, and 178.89
ppm. MS m/z (%): 704 (M+ , 82). Analysis Calcd for C34 H28 N10 O2 S3 (704.16): C, 57.94; H, 4.00; N, 19.87;
Found: C, 57.91; H, 4.01; N, 19.85%.
3.1.3. 5,5′ -(4,4′ -Diphenylsulphone-4,4′ -diyl)-bis-((2-(p-bromobenzylidenehydrazino)-4-methyl-5-
azo-1,3-thiazole) (8c).
Red orange solid; Yield (89%); mp: >300 ◦ C. IR (KBr): νmax 3228 (NH) cm−1 1 H NMR (DMSO-d6): 2.58
.
(s, 6H, 2CH3) 7.45–7.86 (m, 16H, ArH), 8.66 (s, 2H, N=CH), and 10.98 (s, 2H, NH), 13 C NMR (DMSO-d6): at
112.02, 127.15, 128.24, 129.21, 132.02, 132.97, 135.62, 141.28, 143.54, 149.01, 153.37, 161.82, and 173.04 ppm.
MS m/z (%): 862 (M+ , 91). Analysis Calcd for C34 H26 Br2 N10 O2 S3 (862.64): C, 47.34; H, 3.04; N, 16.24;
Found: C, 47.31; H, 3.02; N, 16.27%.
3.1.4. 5,5′ -(4,4′ -Diphenylsulphone-4,4′ -diyl)-bis-((2-(o-hydroxybenzylidenehydrazino)-4-methyl-
5-azo-1,3-thiazole) (9)
Red orange solid; Yield (89%); mp: >300 ◦ C. IR (KBr): νmax 3425 (OH), 3205 (NH) cm−1
.
1 H NMR
(DMSO-d6): 2.57 (s, 6H, 2CH3), 6.91–7.89 (m, 16H, ArH), 8.87 (s, 2H, N=CH), 10.75 (s, 2H, OH), and 10.97
(s, 2H, NH). 13 C NMR (DMSO-d6): 16.62, 114.50, 116.69, 118.75, 119.69, 128.94, 129.99, 133.48, 134.22,
140.17, 146.53, 147.32, 158.59, 160.55, 171.74, and 178.88 ppm. MS m/z (%): 736 (M+ , 74). Analysis Calcd
for C34 H28 N10 O4 S3 (736.15): C, 55.42; H, 3.83; N, 19.01; Found: C, 55.42; H, 3.89; N, 19.02%.
3.1.5. 5,5′ -(4,4′ -Diphenylsulphone-4,4′ -diyl)-bis-((2-(furylidenehydrazino)-4-methyl-5-azo-1,3-
thiazole) (10)
Black green solid; Yield (78%); mp >300 ◦ C. IR (KBr): νmax 3179 (NH) cm−1 1 H NMR (DMSO-d6): 2.58
.
(s, 6H, 2CH3), 6.87–7.98 (m, 18H, ArH, Furan-H), 8.71 (s, 2H, N=CH), and 10.88 (s, 2H, NH), 13 C NMR
(DMSO-d6): at 16.79, 113.77, 115.47, 126.88, 128.14, 132.32, 143.25, 145.65, 146.61, 148.97, 158.52, 164.27,
and 170.01 ppm. MS m/z (%): 684 (M+ , 54). Analysis Calcd for C30 H24 N10 O4 S3 (684.77): C, 52.62; H,
3.53; N, 20.45; Found: C, 52.65; H, 3.57; N, 20.49%.
3.1.6. 5,5′ -(4,4′ -Diphenylsulphone-4,4′ -diyl)-bis-((2-(pyridylidenehydrazino)-4-methyl-5-azo-1,3
-thiazole) (11)
Red brown solid; Yield (89%); mp: 280 ◦ C. IR (KBr): νmax 3246 (NH) cm−1 1 H NMR (DMSO-d6): 2.59 (s,
.
6H, 2CH3), 7.01–7.99 (m, 16H, ArH, Pyridine-H), 8.74 (s, 2H, N=CH), and 10.76 (s, 2H, NH) ppm; m/z (%):
706 (M+ , 69). Analysis Calcd for C32 H26 N12 O2 S3 (706.15): C, 54.38; H, 3.71; N, 23.78; Found: C, 54.41; H,
3.74; N, 23.74%.
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3.1.7. 5,5′ -((Sulfonylbis(4,1-phenylene))bis(diazene-2,1-diyl))bis(4-methyl-2-(2-(1-(thiophen-2-yl)
ethylidene)hydrazinyl)thiazole) (12)
Red solid; Yield (83%); mp: 240 ◦ C. IR (KBr): νmax 3206 (NH), 1592 (C=C) cm−1 1 H NMR (DMSO-d6):
.
2.23 (s, 6H, 2CH3), 2.58 (s, 6H, 2CH3), 7.11–8.19 (m, 14H, ArH, Thiophene-H), and 10.91 (s, 2H, NH), 13 C
NMR (DMSO-d6): at 15.98, 16.81, 114.2, 125.91, 127.78, 129.28, 129.45, 130.29, 134.90, 143.37, 146.59, 162.04,
169.61, and 177.88 ppm. MS m/z (%): 744 (M+ , 75); Anal. Calcd for C32 H28 N10 O2 S5 (744.96): C, 51.59;
H, 3.79; N, 18.80; Found: C, 51.59; H, 3.76; N, 18.83%.
3.1.8. 5,5′ -(Phenyl-1,3-diyl)-bis-((2-(p-methylbenzylidenehydrazino)-4-methyl-5-azo-1,3-thiazole)
(13a)
Red solid; Yield (68%); mp: 178 ◦ C. IR (KBr): νmax 3154 (NH), 1595 (C=C) cm−1 1 H NMR (DMSO-d6):
.
2.38 (s, 6H, 2CH3), 2.50 (s, 6H, 2CH3), 7.14–7.81 (m, 12H, ArH), 8.52 (s, 2H, N=CH), and 10.68 (s, 2H, NH),
13 C NMR (DMSO-d6): at 18.02, 21.60, 113.89, 125.97, 126.86, 127.46, 129.38, 130.44, 132.15, 133.91, 144.12,
150.14, 160.71, and 167.13 ppm. MS m/z (%): 592 (M+ , 90). Analysis Calcd for C30 H28 N10 S2 (592.74): C,
60.79; H, 4.76; N, 23.63; Found: C, 60.75; H, 4.79; N, 23.61%.
3.1.9. 5,5′ -(Phenyl-1,3-diyl)-bis-((2-(benzylidenehydrazino)-4-methyl-5-azo-1,3-thiazole) (13b)
Red solid; Yield (91%); mp: 200 ◦ C. IR (KBr): νmax 3165 (NH), 1608 (C=N) cm−1 1 H NMR (DMSO-d6):
.
2.51 (s, 6H, 2CH3) 7.03–7.84 (m, 14H, ArH), 8.55 (s, 2H, N=CH), and 10.86 (s, 2H, NH), 13 C NMR (DMSO-
d6): at 21.01, 112.19, 115.38, 126.27, 127.24, 128.62, 129.99, 130.62, 131.24, 138.23, 139.32, 149.63, and 166.62
ppm; m/z (%): 564 (M+ , 29). Analysis Calcd for C28 H24 N10 S2 (564.69): C, 59.56; H, 4.28; N, 24.80; Found:
C, 59.52; H, 4.27; N, 24.83%.
3.1.10. 5,5′ -(Phenyl-1,3-diyl)-bis-((2-(p-bromobenzylidenehydrazino)-4-methyl-5-azo-1,3-thiazole)
(13c)
Red solid; Yield (88%); mp: >300 ◦ C. IR (KBr): νmax 3194 (NH), 1593 (C=C) cm−1 1 H NMR (DMSO-d6):
.
2.64 (s, 6H, 2CH3), 7.23–7.95 (m, 12H, ArH), 8.71 (s, 2H, N=CH), and 10.98 (s, 2H, NH), 13 C NMR (DMSO-
d6): at 20.06, 112.01, 113.65, 126.45, 127.32, 128.61, 129.84, 132.70, 138.66, 142.12, 143.06, 151.64, and 167.11
ppm. MS m/z (%): 722 (M+ , 27). Analysis Calcd for C28 H22 Br2 N10 S2 (722.48): C, 46.55; H, 3.07; N, 19.39;
Found: C, 46.51; H, 3.04; N, 19.41%.
3.1.11. 5,5′ -(Phenyl-1,3-diyl)-bis-((2-(o-hydroxybenzylidenehydrazino)-4-methyl-5-azo-1,3-thia-
zole) (14)
Red brown solid; Yield (75%); mp: >300 ◦ C. IR (KBr): νmax 3433 (OH), 3182 (NH), 1609 (C=N) cm−1 1 H
.
NMR (DMSO-d6): 2.66 (s, 6H, 2CH3), 7.43–7.96 (m, 12H, ArH), 8.81 (s, 2H, N=CH), 10.77 (s, 2H, NH), and
10.97 (s, 2H, NH) ppm. MS m/z (%): 596 (M+ , 88). Analysis Calcd for C28 H24 N10 O2 S2 (596.69): C, 56.36;
H, 4.05; N, 23.47; Found: C, 56.39; H, 4.03; N, 23.49%.
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3.1.12. 5,5′ -(Phenyl-1,3-diyl)-bis-((2-(furylidenehydrazino)-4-methyl-5-azo-1,3-thiazole) (15)
Deep green solid; Yield (63%); mp: >300 ◦ C. IR (KBr): νmax 3198 (NH), 1613 (C=N) cm−1
.
1 H NMR
(DMSO-d6): 2.71 (s, 6H, 2CH3), 6.84–8.02 (m, 10H, ArH), 8.73 (s, 2H, N=CH), and 10.88 (s, 2H, NH) ppm.
MS m/z (%): 544 (M+ , 19). Analysis Calcd for C24 H20 N10 O2 S2 (544.61): C, 52.93; H, 3.70; N, 25.72; Found:
C, 52.95; H, 3.72; N, 25.75%.
3.1.13. 5,5′ -(Phenyl-1,3-diyl)-bis-((2-(pyridylidenehydrazino)-4-methyl-5-azo-1,3-thiazole) (16)
Red brown solid; Yield (79%); mp: >300 ◦ C. IR (KBr): νmax 3181 (NH), 1603 (C=N) cm−1
;
1 H NMR
(DMSO-d6): 2.78 (s, 6H, 2CH3), 6.78–7.99 (m, 12H, ArH), 8.75 (s, 2H, N=CH), and 10.86 (s, 2H, NH) ppm.
MS m/z (%) = 566 (M+ , 22). Analysis Calcd for C26 H22 N12 S2 (566.66): C, 55.11; H, 3.91; N, 29.66; Found:
C, 55.14; H, 3.93; N, 29.68%.
3.1.14. 1,3-Bis((4-methyl-2-(2-(1-(thiophen-2-yl)ethylidene)hydrazinyl)thiazol-5-yl)diazenyl)ben-
zene (17)
Red solid; Yield (91%); mp: 185 ◦ C. IR (KBr): νmax 3177 (NH), 1596 (C=C) cm−1 1 H NMR (DMSO-d6):
.
2.25 (s, 6H, 2CH3), 2.74 (s, 6H, 2CH3), 6.99–8.01 (m, 10H, ArH), and 10.97 (s, 2H, NH), 13 C NMR (DMSO-
d6): at 16.73, 21.59, 114.18, 123.87, 127.25, 128.45, 128.72, 130.49, 132.46, 134.32, 142.32, 157.23, 159.84, and
171.24 ppm. MS m/z (%): 604 (M+ , 88). Analysis Calcd for C26 H24 N10 S4 (604.8): C, 51.63; H, 4.00; N,
23.16; Found: C, 51.65; H, 4.03; N, 23.19%.
3.2. General procedure for the synthesis of 20 and 22
A mixture of bis-hydrazoyl halides 1 or 2 (5 mmol) and dimethyl acetylenedicarboxylate 19 (1.42 mL, 10 mmol)
in dioxane (20 mL) and triethylamine (1 g, 1.5 mL, 10 mmol) was boiled under reflux for 4 h. The reaction
mixture was then poured into ice-cold hydrochloric acid with stirring. The solid that precipitated was collected.
The resulting solid, which formed after cooling, was collected and crystallized from DMF/EtOH to give 20 and
22 elucidated by elemental spectral analyses.
3.2.1. Tetramethyl-1,1′ -(sulfonylbis(4,1-phenylene))bis(3-acetyl-1H-pyrazole-4,5-dicarboxylates)
(20).
Brown solid; Yield (65%); mp: 173 ◦ C. IR (KBr): νmax 1741, 1661 (C=O), 1597 (C=C) cm−1
.
1 H NMR
(DMSO-d6): 2.49 (s, 6H, CH3), 3.88 (s, 6H, CO2 CH3), 4.08 (s, 6H, CO2 CH3), 7.02–8.23 (m, 8H, ArH), 13
C
NMR (DMSO-d6): at 26.62, 52.15, 53.64, 122.65, 127.69, 128.24, 138.06, 139.28, 145.68, 152.02, 160.01, 163.25,
and 195.27 ppm. MS m/z (%): 666 (M+ , 17). Analysis Calcd for C30 H26 N4 O12 S (666.60): C, 54.05; H, 3.93;
N, 8.40; Found: C, 54.02; H, 3.95; N, 8.44%.
3.2.2. Tetramethyl-1,1′ -(1,3-phenylene)bis(3-acetyl-1H-pyrazole-4,5-dicarboxylates) (22)
Brown solid; Yield (54%); mp 120 ◦ C. IR: νmax 1739, 1671 (C=O), 1594 (C=C) cm−1
.
1 H NMR (DMSO-
d6): 2.52 (s, 6H, CH3), 3.93 (s, 6H, CO2 CH3), 4.15 (s, 6H, CO2 CH3), 7.36–8.02 (m, 4H, ArH), 13 C NMR
(DMSO-d6): at 26.74, 52.98, 53.31, 107.69, 124.93, 128.07, 130.29, 138.09, 140.68, 148.71, 158.69, 163.76, and
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192.31 ppm; m/z (%): 526 (M+ , 23); Anal. Calcd for C24 H22 N4 O10 (526.50): C, 54.75; H, 4.21; N, 10.64;
Found: C, 54.79; H, 4.24; N, 10.61%.
3.3. Synthesis of thiohydrazonate derivatives 24 and 25
A mixture of bis-hydrazonoyl dichlorides 1 or 2 (5 mmol) and 4-bromophenol 23 (1.881 g, 11 mmol) in NaOMe
(20 mL, 11 mmol) was stirred at room temperature for 30 h. The solid that precipitated was collected. The
resulting solids filtered, washed with water, and recrystallized from DMF/MeOH.
3.3.1. N,N′ -(Sulfonyl)-bis-(1,4-phenylene)-bis-(4-bromophenyl-2-oxopropanehydrazonoate) (24)
Black green solid; Yield (83%); mp: >300 ◦ C. IR (KBr): νmax 3228 (NH), 1661 (C=O), 1591 (C=C) cm−1
.
1 H NMR (DMSO-d6): 2.49 (s, 6H, 2CH3), 7.21–8.18 (m, 16H, ArH), 9.64 (s, 2H, NH), 13 C NMR (DMSO-d6):
at 26.70, 96.76, 119.01, 126.67, 128.81, 129.21, 129.64, 141.03, 142.17, 163.58, and 208.11 ppm. MS m/z (%):
728 (M+ , 19). Analysis Calcd for C30 H24 Br2 N4 O6 S (728.40): C, 49.47; H, 3.32; N, 7.69; Found: C, 49.49;
H, 3.35; N, 7.72%.
3.3.2. N,N′ -(1,3-Phenylene)-bis-(4-bromophenyl-2-oxopropanehydrazonoate) (25)
Red brown solid; Yield (72%); mp: >300 ◦ C. IR (KBr): 3194 (NH), 1672 (C=O), 1603 (C=N) cm−1
.
1 H
NMR (DMSO-d6): 2.50 (s, 6H, 2CH3), 7.41–7.99 (m, 12H, ArH), 9.73 (s, 2H, NH) ppm. MS m/z (%): 588
(M+ , 18). Analysis Calcd for C24 H20 Br2 N4 O4 (588.2): C, 49.00; H, 3.43; N, 9.52; Found: C, 49.03; H, 3.46;
N, 9.49%.
3.4. Synthesis of bis-triazolo[3,4-b]thiadiazole (29a–c)
To a solution of the bis-hydrazones 27 (2.5 mmol) in ethanol (40 mL) was added a solution of iron(III) chloride
(5 mL, 2 M). The reaction mixture was heated at reflux for 30 min and then left to stir overnight at room
temperature. The excess solvent was distilled under reduced pressure and the solid residue left was collected
and washed with water several times, dried, and finally crystallized from methanol to give the respective
compounds 29a–c.
3.4.1. 3,6-Di(4-methyphenyl)-bis-triazolo[3,4-b]thiadiazole (29a)
Brown solid, Yield (65%); mp: 225 ◦ C. IR (KBr): νmax 1604 (C=N) cm−1 . 1 H NMR (DMSO-d6): δ 2.38 (s,
6H, 2CH3), 7.11–8.05 (4d, J8 Hz, 8H, ArH), 13 C NMR (DMSO-d6): at 21.16, 128.14, 129.49, 129.74, 130.74,
143.34, and 162.01 ppm. MS m/z (%): 346 (M+ , 46). Analysis Calcd for C18 H14 N6 S (346.41): C, 62.41; H,
4.07; N, 24.26. Found: C, 62.39; H, 4.06; N, 24.21%.
3.4.2. 3,6-Di(diphenyl)-bis-triazolo[3,4-b]thiadiazole (29b)
Red brown solid, Yield (72%); mp: 199 ◦ C. IR (KBr): νmax 1602 (C=N) cm−1
.
1 H NMR (DMSO-d6): δ
7.38–8.01 (m, 10H, ArH), 13 C NMR (DMSO-d6): at 128.46, 128.87, 129.46, 132.80, 144.12, and 163.24 ppm;
m/z (%): 318 (M+ , 31). Analysis Calcd for C16 H10 N6 S (318.07): C, 60.36; H, 3.17; N, 26.40. Found: C,
60.34; H, 3.21; N, 26.42%.
608

SAYED/Turk J Chem
3.4.3. 3,6-Di(4-chlorophenyl)-bis-triazolo[3,4-b]thiadiazole (29c)
Yellow brown solid, Yield (86%); mp: 207 ◦ C. IR (KBr): νmax 1593 (C=C) cm−1
.
1 H NMR (DMSO-d6): δ
7.24–8.13 (m, 8H, ArH), 13 C NMR (DMSO-d6): at 128.68, 128.45, 129.94, 134.97, 152.14, and 168.01 ppm.
MS m/z (%): 385 (M+ , 43). Analysis Calcd for C16 H8 Cl2 N6 S (385.99): C, 49.63; H, 2.08; N, 21.70. Found:
C, 49.65; H, 2.11; N, 21.68%.
4. Conclusion
In summary, thiazoles derivatives were prepared from thiosemicarbazone with α-halocarbonyl hydrazonoyl.
The synthesis of pyrazoles was achieved by reaction of dimethyl acetylenedicarboxylate with bis-hydrazonoyl
chlorides. Thiohydrazonates 24 and 25 were also prepared via reaction of 4-bromophenol with bis-hydrazonoyl
chlorides. In addition, bis-triazolothiadiazoles were synthesized via oxidative cyclization of bis-hydrazones.
Acknowledgment
The financial support from the Deanship of Scientific Research (Project Number 140093), King Faisal University,
Saudi Arabia, is gratefully acknowledged.
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