Synthesis and characterization of new pyrazole-based thiazoles

Article abstract of DOI:10.1080/00397911.2017.1330961

A series of new 5-(heteroaryldiazenyl)thiazole incorporating pyrazole moiety have been synthesized through coupling of the thiazole with the appropriate heteroaryldiazonium salts. The newly synthesized compounds were characterized by elemental analysis, s

Full text of DOI:10.1080/00397911.2017.1330961

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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Synthesis and Characterization of New Pyrazole
Based Thiazoles
Abdou O. Abdelhamid & Sobhi M. Gomha
To cite this article: Abdou O. Abdelhamid & Sobhi M. Gomha (2017): Synthesis and
Characterization of New Pyrazole Based Thiazoles, Synthetic Communications, DOI:
10.1080/00397911.2017.1330961
To link to this article: http://dx.doi.org/10.1080/00397911.2017.1330961
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Date: 25 May 2017, At: 12:26

SYNTHESIS AND CHARACTERIZATION OF NEW PYRAZOLE BASED
THIAZOLES
Abdou O. Abdelhamid1, Sobhi M. Gomha1
1Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
Correspondence: Sobhi M. Gomha. E-mail: s.m.gomha@gmail.com
Abstract
A series of new 5-(heteroaryldiazenyl)thiazole incorporating pyrazole moiety have been
synthesized via coupling of the thiazole with the appropriate heteroaryldiazonium salts.
The newly synthesized compounds were characterized by elemental analysis,
spectroscopic (IR, 1H NMR, and Mass) data and alternative synthesis whenever possible.
GRAPHICAL ABSTRACT
KEYWORDS: Thiazoles; pyrazoles; coupling reaction; thiosemicarbazide.
INTRODUCTION
Pyrazoles and their variously substituted derivatives are important biological agents and a
significant amount of research activity has been directed towards this class. In particular,
1

they are used as antitumor, antibacterial and antifungal, antiviral, antiparasitic, anti-
tubercular, insecticidal, anti-inflammatory, anti-diabetic, anesthetic and analgesic
agents.[1–13] Also, thiazoles are important class of heterocyclic compounds, found in many
potent biologically active molecules such as Sulfathiazol (antimicrobial drug), Ritonavir
(antiretroviral drug), Abafungin (antifungal drug) with trade name Abasol cream and
Bleomycine and Tiazofurin (antineoplastic drug). It has been noticed continuously over
the years that interesting biological activities[14,15] were associated with thiazole
derivatives. Recently, the applications of thiazoles were found in drug development for
the treatment of allergies, inflammation, schizophrenia, bacterial, hypnotics and more
recently for the treatment of pain, as fibrinogen receptor antagonists with antithrombotic
activity and as new inhibitors of bacterial DNA gyrase B.[16-27] In continuation to our
interest in the chemical and pharmacological properties of pyrazole and thiazole
derivatives,[28-37] we report herein a facile synthetic strategy for preparation of some new
thiazole derivatives linked to pyrazole moiety. The biological activities of the synthesized
products will be reported in extended work.
RESULTS AND DISCUSSION
The required 2-(1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethylidene)hydrazine-1-
carbothioamide (1) was prepared following the literature method. [38] Compound 1 used
as useful intermediate for synthesis of different heterocyclic compounds, thus, cyclization
of 1 with various α-bromoketones in ethanol under reflux yielded the respective thiazole
derivatives 3a-e (Scheme 1). The elemental analysis together with the data derived from
IR, 1H NMR and mass spectra are in agreement with the proposed structure 3. 1H NMR
2

of compound 3b, taken as a typical example, showed signals at δ 2.31 (s, 3H, CH3), 2.50
(s, 3H, CH3), 7.42-8.07 (m, 12H, Ar-H and thiazole H-5), 8.12 (s, 1H, pyrazole H-3),
8.42 (s, 1H, naphthalene H-1), 10.28 (s, br, 1H, NH). The mass spectrum of each of
products 3 revealed the presence of a molecular ion peak (m/z) which is consistent with
the structure of the respective compound (see experimental section). Coupling of thiazole
derivatives 3a-e with arenediazonium chlorides in ethanol containing sodium acetate at 0-
5 oC, yielded 5-arylazothiazole derivatives 4a-h. Structures 4a-h were confirmed by
elemental analysis, spectral data and alternative synthesis. Thus, reaction of
thiosemicarbazone derivative 1 with (Z)-2-oxo-N,2-diphenylacetohydrazonoyl bromide
(5)[39] in dioxane in the presence of triethylamine as a basic catalyst gave a product
identical in all aspects (mp., mixed mp., and spectra) with 4a.
Analogously, reaction of compound 1 with chloroacetone 6 in refluxing ethanol, gave
thiazole derivative 7 based on elemental analysis and spectral data. Coupling of the latter
compound with arenediazonium chloride in ethanolic sodium acetate afforded thiazoles
derivatives 4i-n, respectively(Scheme 2). The structures of the latter products 4i-n were
evidenced by microanalysis and spectral (IR, 1H NMR, Mass) data. For example, 1H
NMR displayed in each case five singlet signals near δ 2.18, 2.48, 8.73, 7.96 and 10.36
assigned for the three methyl groups, pyrazole-H3 and NH proton, in addition to the
expected signals characteristic for the aryl protons (see experimental). Also, the mass
spectra of products 4i-n revealed in each case a molecular ion peak which consistent with
the molecular formula of the assigned structure.
3

Compound 3a was reacted with diazotized benzidine 8 in ethanolic sodium acetate
afforded 4,4'-bis (2-(2-(1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethylidene)hydrazinyl)-4-
phenylthiazol-5-yl)diazenyl)-1,1'-biphenyl (9) (Scheme 3). Structure 9 was elucidated by
elemental analysis, spectral data. 1H NMR spectra of 9 showed signals at δ 2.33 (s, 6H,
CH3), 2.64 (s, 6H, CH3), 7.19-7.66 (m, 28H, Ar-H), 8.10 (s, 2H, pyrazole H-3), 10.38 (s,
br, 2H, NH).
Finally, compound 3a was coupled with diazotized 3-amino-4-cyanopyrazole 10 in
ethanolic sodium acetate solution gave pyrazolyl-azothiazole derivative 11 (Scheme 4).
Structure 11 was elucidated via elemental analysis and spectral data. IR (cm-1) spectrum
of 11 revealed peaks at 3427, 3312 (2NH), 2227 (CN) and its 1H NMR showed signals at
δ 2.22, 2.62 (2s, 6H, 2CH3), 7.13-7.65 (m, 10H, Ar-H), 7.88 (s, H, pyrazole H-3), 8.04 (s,
H, pyrazole H3), 9.23 (s, br, 1H, NH), 10.33 (s, br, 1H, NH).
Analogously, the appropriate diazotized heterocyclic amines 12, 14, 16 were coupled
with 3a afforded triazolyl-azothiazole derivative 13, benzoimidazolyl-azothiazole
derivative 15 and pyrazolopyridyl-azothiazole derivative 17, respectively (Scheme 4).
The structures assigned for the products 13, 15 and 17 were confirmed based on
elemental analysis and spectroscopic data (see experimental).
General Procedure For Synthesis Of Thiazoles 3a-E
To a solution of thiosemicarbazone 1 (0.273 g, 1 mmol) in ethanol (20 mL), bromoacetyl
derivatives 2a-e (l0 mmol) were added. The mixture was refluxed for 4-8 h (monitored
4

by TLC), then left to cool. The solid product was filtered off, washed with ethanol and
recrystalized from ethanol or dioxane to afford the thiazole derivatives 3a-e, respectively.
The products 3a-e together with their physical constants are listed below.
2-(2-(1-(5-Methyl-1-Phenyl-1H-Pyrazol-4-Yl)Ethylidene)Hydrazinyl)-4-
(Naphthalen-2-Yl)Thiazole (3b)
White solid, (72% yield); mp 170-172 °C; IR (KBr) υ 3196 (NH), 1600 (C=N) cm-1; 1H
NMR (300 MHz, DMSO-d6) δ 2.31 (s, 3H, CH3), 2.50 (s, 3H, CH3), 7.42-8.07 (m, 12H,
Ar-H and thiazole H-5), 8.12 (s, 1H, pyrazole-H3), 8.42 (s, 1H, naphthalene-H1), 10.28
(s, br, 1H, NH); MS, m/z (%) 424 (M++1, 34), 423 (M+, 42), 256 (73), 167 (61), 112 (30),
77 (100), 57 (78). Anal. calcd for C25H21N5S (423.53): C, 70.90; H, 5.00; N, 16.54;
found: C, 70.97; H, 4.92; N, 16.43%.
CONCLUSIONS
We have developed a simple and convenient method for the synthesis of 4-substituted-2-
(2-(1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethylidene)hydrazinyl)-5-
(heteroaryldiazenyl)thiazole and 4,4'-bis(2-(2-(1-(5-methyl-1-phenyl-1H-pyrazol-4-
yl)ethylidene)hydrazinyl)-4-phenylthiazol-5-yl)diazenyl)-1,1'-biphenyl via coupling of
thiazole derivatives with the appropriate heteroaryldiazonium salts. Also, the structures of
all the newly synthesized products were confirmed based on elemental analysis, spectral
data and by alternative methods.
SUPPLEMENTAL MATERIAL
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Supplemental data for this article can be accessed on the publisher’s website.
CONFLICTS OF INTEREST
The authors declare no conflict of interest.
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Scheme 1. Synthesis of thiazoles 3a-e and its azo derivatives 4a-h
10

Scheme 2. Synthesis of thiazole 7 and its azo derivatives 4i-n
11

Scheme 3. Synthesis of bis-thiazole 9
12

Scheme 4. Synthesis of thiazoles 11, 13, 15 and 17
13