Novel, Simple, and Efficient Synthesis of 3-(2-(5-(Benzylideneamino)-3-phenyl-1H-pyrazol-1-yl)thiazol-4-yl)-4-hydroxy-6-methyl-2H-pyran-2-one Derivatives via a One-Pot, Four-Component Condensation Reaction

Abstract The synthesis of 3-(2-(5-(benzylideneamino)-3-phenyl-1H-pyrazol-1-yl)thiazol-4-yl)-4-hydroxy-6-methyl-2H-pyran-2-one derivatives was achieved through a one-pot, four-component reaction involving condensation of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, thiosemicarbazide, phenacylcyanaide, and various aryl aldehydes in dry alcohol and few drops of acetic acid under reflux condition. This four-component reaction has some advantages such as ease of handling, good yields, and easy workup. All structures of newly prepared compounds were confirmed by analytical and spectral data. GRAPHICAL ABSTRACT


INTRODUCTION
Pyrazole and thiazole derivatives are used in medicine because of their large number of pharmacological activities. [1] Pyrazole and its derivatives constitute an important class of compounds and attract widespread attention because of pharmacological properties such as analgesic and anti-inflammatory properties. [2,3] The pyrazole moiety has an important role in some drug structures; for example, some arylpyrazole derivatives have anti-HIV-1 activity. [4][5][6] Thiazoles are an important class of natural and synthetic compounds. Thiazoles and their derivatives have been reported to possess antibacterial, [7] antifungal, [8] antioxidant, [9] anti-HIV, [10] and antiallergic [11] activities.
Recently, multicomponent reactions (MCRs) [12] have played a significant role in modern synthetic organic chemistry wherein three or more reactants are added together in one pot to result in diverse bioactive heterocyclic compounds. Multicomponent reactions have emerged as an important tool for building diverse and complex organic molecules through carbon-carbon and carbon-heteroatom bond formation, which takes place in a tandem manner. [13] We designed the synthesis of novel substituted pyrazolo thiazolyl derivatives starting from bromodehydroacetic acid, phenacylcyanaide, thiosemicarbazide, and various araldehydes.

RESULTS AND DISCUSSION
This is a one-pot, four-component synthesis of substituted pyrazolo thiazole derivatives. Refluxing an equimolar mixture of 3-(2-bromoacetyl)-4-hydroxy-6methyl-2H-pyran-2-one, thiosemicarbazide and phenacylcyanaide in absolute ethanol and few drops of glacial acetic acid for 4 h resulted in the formation of amino derivatives. These undergo condensation with various benzaldehydes to give the final products 3-(2-(5-(benzylideneamino)-3-phenyl-1H-pyrazol-1-yl)thiazol-4-yl)-4hydroxy-6-methyl-2H-pyran-2-one derivatives 5 (Scheme 1). The importance of this reaction is that two rings like thiazole and pyrazole are formed simultaneously, wherein the first step is Hantzsch thiazole synthesis and the next step is formation of a pyrazole ring at the second position of the thiazole ring. This is a novel observation and new heterocyclization reactions form many bonds at a time.

PYRAZOLO-THIAZOLYL DERIVATIVES 2351
with various benzaldehydes to give corresponding title compound 5 as shown in Scheme 2.
In the IR spectrum of 5a, the OH appeared at 3422 cm À1 , lactone carbonyl at 1721 cm À1 , and C=N at 1607 cm À1 , respectively. The 1 H NMR spectrum of 5a showed five singlets at d ¼ 2.23, 6.17, 6.89, 8.26, and 12.32 ppm, which were due to methyl, pyran, pyrazole, -ArCH=N, hydroxy protons, and multiplets at d ¼ 7.24-7.71 ppm for nine aromatic protons and one thiazole proton respectively. In the mass spectrum 5a showed at [M þH] þ ion at m=z 489.

EXPERIMENTAL
All the reagents, solvents, and 3-oxo-3-phenylpropanenitrile were purchased from commercial sources and were used without any further purification unless otherwise stated. 3-(2-Bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one [14] was prepared The reaction mixture was refluxed for 4 h and then cooled to room temperature. The solid obtained was filtered, washed with water, and recrystallized from methanol to give excellent yields of products (Table 1)

FUNDING
The authors are thankful to the director of the National Institute of Technology, Warangal, India, for providing financial support and facilities.

SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher's website.