Synthesis and Bioactivity of Pyrazole Acyl Thiourea Derivatives

Jian Wu,Ming He,Zhuo Chen,Linhong Jin,Qing Shi,Deyu Hu

doi:10.3390/molecules17055139

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, 1H-NMR, 13C-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.

Highlights

Many acyl thiourea derivatives are well known to possess a wide range of bioactivities and are often employed as fungicidal, antiviral and regulating activities for plant protection in agriculture [1,2,3].Some of them are employed as commercial insecticides [4], herbicides [5,6] and fungicides [7,8]
PEG-400 as a phase transfer catalyst is indispensable for these reactions; it can react with NH4SCN to form a
[PEG-400-NH4+] SCN−complex, which make it possible for SCN− to readily react with 5-chloro-1,3dimethyl-1H-pyrazole-4-carbonyl chloride and lead to the formation of intermediates 5a

Summary

Introduction

Many acyl thiourea derivatives are well known to possess a wide range of bioactivities and are often employed as fungicidal, antiviral and regulating activities for plant protection in agriculture [1,2,3].Some of them are employed as commercial insecticides [4], herbicides [5,6] and fungicides [7,8]. Many acyl thiourea derivatives are well known to possess a wide range of bioactivities and are often employed as fungicidal, antiviral and regulating activities for plant protection in agriculture [1,2,3]. Several novel N'-(substituted pyrimidin-2-yl)-N-chrysanthemoylthiourea derivatives were synthesized by Xu’s group in 2005, and preliminary biological indicated that compounds I (Figure 1) exhibited 90% and. Compounds II and III (Figure 1), arylthioureas containing 1,3,4-thiadiazole moieties, were found to show good plant growth regulator activity at 10 μg/mL [10,11]; Wang et al [12] reported that acyl thiourea derivatives. Compound VI (Figure 1) that can be prepared by a multi-step reaction sequence using 2-chloro-5-(chloromethyl) pyridine, displayed 96.4% and 85.3% activities against rape root and barnyard root at 10 μg/mL, respectively [14]

Methods

Results

Conclusion