Synthesis and antifungal study of novel fluoro-benzothiazole derivatives

N-{6-fluoro-7-[(substituted)-amino] 1, 3-benzothiazole-2-yl}-2-nitrobenzamides; N-{6-fluoro-7-[(substituted)-amino] 1, 3-benzothiazole-2-yl}-3-nitrobenzamides and N-{6-fluoro-7-[(substituted)-amino] 1, 3-benzothiazole-2-yl}-4-nitrobenzamides derivatives were synthesized. The synthesized compounds were screened for antifungal activity at two different concentrations (50μg/ml, 100μg/ml) against Candida albicans and Aspergillus niger by cup plate method (diffusion technique) using Griseoflavin as standard.RESULTAND DISCUSSTIONIn present work, fluorochloro aniline was treated with potassium thiocynate in presence of bromine in glacial acetic acid and ammonia to get 2-amino-6-fluro-7-chloro (1, 3)-benzothiazole which was condensed with 2 (3 or 4)-nitrobenzoylchloride acid in presence of dry pyridine and acetone to get N-(7-chloro-6-fluoro-1, 3-benzothiazole-2-yl)-2 (3 or 4)-nitrobenzamides. To the above product 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, o-toludine,m-toludine, p-toludine, 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, 2- aminophenol, 3-aminophenol, 4-aminophenol, 2-anisidine, 3-anisidine and 4-anisidine in presence of DMF were treated to get newly synthesized N-{6-fluoro-7-[(substituted)-amino] 1, 3-benzothiazole-2-yl}-4-nitrobenzamides derivatives through replacing at 7th position chlorine. Reaction progress was monitored by thin layer chromatography.Melting points of the synthesized compounds were determined in open capillaries and showed a minute change after recrystallisation. IR spectra (KBr pellet technique) were recorded using a SHIMADZU (8400S), spectrophotometer.

N-{6-氟-7-[(取代)氨基]-1,3-苯并噻唑-2-基}-2-硝基苯甲酰胺、N-{6-氟-7-[(取代)氨基]-1,3-苯并噻唑-2-基}-3-硝基苯甲酰胺以及N-{6-氟-7-[(取代)氨基]-1,3-苯并噻唑-2-基}-4-硝基苯甲酰胺衍生物已成功合成。所合成的化合物采用杯碟法（扩散技术，Cup Plate Method），以灰黄霉素（Griseoflavin）为标准对照品，设置50μg/ml、100μg/ml两个浓度，针对白色念珠菌（Candida albicans）与黑曲霉（Aspergillus niger）开展抗真菌活性筛选。
结果与讨论
本研究中，将氟氯苯胺与硫氰酸钾在冰乙酸、氨水及溴素存在的体系中反应，得到2-氨基-6-氟-7-氯-(1,3)-苯并噻唑；随后将该产物与2(3或4)-硝基苯甲酰氯在干燥吡啶与丙酮的混合溶剂中缩合，得到N-(7-氯-6-氟-1,3-苯并噻唑-2-基)-2(3或4)-硝基苯甲酰胺。将上述产物分别与2-氯苯胺、3-氯苯胺、4-氯苯胺、邻甲苯胺、间甲苯胺、对甲苯胺、2-硝基苯胺、3-硝基苯胺、4-硝基苯胺、2-氨基苯酚、3-氨基苯酚、4-氨基苯酚、2-茴香胺、3-茴香胺及4-茴香胺在N,N-二甲基甲酰胺（DMF）中反应，通过取代7位的氯原子，得到系列新型N-{6-氟-7-[(取代)氨基]-1,3-苯并噻唑-2-基}-4-硝基苯甲酰胺衍生物。反应进程通过薄层色谱法（Thin Layer Chromatography, TLC）进行监测。所合成化合物的熔点采用开口毛细管法测定，重结晶后熔点仅发生微小变化。红外光谱（IR）采用溴化钾压片法（KBr pellet technique），通过岛津（SHIMADZU）8400S型分光光度计完成采集。