Synthesis and Bioactivity of Pyrazole Acyl Thiourea Derivatives

Abstract

Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, 1 H-NMR, 13 C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.

Characterization of some amino acid derivatives of benzoyl isothiocyanate: Crystal structures and theoretical prediction of their reactivity

“…The product was recrystallized from ethanol:toluene (1:1) and obtained as a brown solid. Yield ¼ 55e68%, Mp ¼ 240e242 C. 1 …”

“…The isothiocyanates can be generated by a reaction of the acylated intermediates with ammonium thiocyanate in the presence of polyethylene gylcol 400 (PEG 400) [1], and then reacted with amines to generate the thiourea derivatives. Thiourea derivatives have been synthesized through several ways.…”

“…A series of thiourea derivatives containing the quinazolinee4(3H) framework have been synthesized by Saeed et al [4]. Pyrazole acyl thiourea derivatives have also been synthesized from monomethylhydrazine (or phenylhydrazine) and ethyl acetoacetate [1]. N-(5-Aryl-2-furonyl) thiourea derivatives containing substituted pyrimidine rings have been synthesized in good yield using PEGe400 as a phase transfer catalyst under ultrasonic irradiation [5].…”

A review on the chemistry, coordination, structure and biological properties of 1-(acyl/aroyl)-3-(substituted) thioureas

“…This reaction is usually carried out in dry acetone or acetonitrile; however, other conditions have also been used including ionic liquids like 1-butyl-3-methylimidazolium tetrafluoroborate-, [18] PEG-400 [19] or solvent-free conditions. [ Scheme 2.…”

Green synthesis of pyrazole systems under solvent-free conditions

“…In most of these methods, diverse organic solvents such as ethanol, toluene, CH 2 Cl 2 , acetone and acetonitrile have been used (22)(23)(24)(25)(26)(27)(28)(29)(30)(31). The obtained product yields of most of these reactions are significant, but the solvents used are not compatible with the environment or cost savings.…”