Synthesis, Crystal Structure And Biological Activity Of (E)-N-benzylidene-4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine

A series of thiazole Schiff bases with different functional groups were designed and synthesized. All new compounds were comfirmed by1H NMR and underwent biological activity tests.Schiff base, which was first discovered by Schiff in 1864, is synthesized by aldehyde or ketone carbonyl and primary amine, hydrazine or its derivatives of the-NH2 group. Because of its special structure, Schiff base can form complexes with most metal ions, which have important applications in medicine, catalysis, analytical chemistry, anti-corrosion and photochromic. Schiff bases also have bacteriostatic, bactericidal, anti-tumor, anti-viral biological activity. As the heterocyclic compounds, thiazole compounds are widely used as local anesthetic, antibiotics, antitumor drugs, etc. Similarly, Thiazole compounds has very good pesticide activity. There are more than 40 fungicides with thiazole ring.The Compound 3,3-dimethyl-l-(1H-1,2,4-triazol-1-yl)butan-2-one was synthesized by 2-(chloromethyl)-4-methylpent-l-ene reacted with 1,2,4-triazole to give then through the reactions of bromination with Br2 and cyclization with thiourea, finally, antacided with ammonia to give the (E)-N-benzylidene-4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine (1). The salicylaldehyde through halogenation or nitration give 5 kinds of salicylaldehyde derivatives. Nine (E)-N-benzylidene-4-(tert-butyl)-5-(1H-1,2,4-triazol-l-yl) thiazol-2-amine derivatives were designed and synthesized by 1 reacting with Aromatic aldehyde. Twenty five of 5-benzyl 4-tert-butyl-2-benzyl sub-aminothiazole were designed and synthesized. The influence of 2-amine-thiazol was investigated.The crystal structure of 1、2 and 10 was determined by single-crystal X-ray. The molecular and crystal structures of 1 are stabilized by an intermolecular N-H…N hydrogen bond. Intramolecular O-H…N hydrogen bond between the Schiff base and hydroxy group was observed in the crystal of 2. The molecular and crystal structures of 10 are stabilized by van der vaals force.The biological anti-tumor activity and fungicidal activity test of the new compouds were carried. The results of preliminary bioassay indicated that the title compound possesses potential anti-tumor activity toward HELA cell, BEL 7402 cell, CNE 2 cell. The preliminary bioassay of compound 2-10 showed that 4,5 and 6 have good fungicidal activity. The EC50 of 6 to Gibberella zeae, Rhizoctonia solani and Sclerotonia sclerotiorum are 1.16 mg/L,1.47 mg/L and 1.38 mg/L resprctively.