Synthesis and characterization of new compounds derived from 2-hydrazinobenzothiazole and evaluated their antibacterial activity

A series of new benzothiazole hydrazide derivatives starting from 2-mercaptobenzothiazole have been synthesized. 2-hydrazinobenzothiazole [M1] was prepared by refluxing of a mixture of hydrazine hydrate. H2O (80%) with 2-mercaptobenzothiazole. The reaction of the compound [M1] with the synthesized esters and amino esters [M2-M7 afforded benzothiazole hydrazide derivatives [M8-M13]. Compounds [M2-M7] were prepared from the reaction of different amino acids and carboxylic acids with absolute ethanol in presence of concentrated sulfuric acid. The structures of all synthesized compounds were established on the basis of FT-IR and some of them by 1H-NMR. The synthesized compounds have been evaluated for antimicrobial activity against Gram-positive and Gram-negative bacteria. Among thirteen synthesized compounds, in which four compounds (M8-M12) exhibited promising antibacterial activity.


Introduction
2-Hydrazine benzothiazole is a bicyclic ring system [1,2] bonded to the hydrazide group. Benzothiazole derivatives have been studied overall and take much interest. Its consider a core structure for the synthesis of new benzothiazole derivatives [3], this due to their several chemical reactivities and the potent broad spectrum of biological activity [4,5,6] such as anti-nociceptive [7], antitumor agents [8], antimicrobial [9], anti-inflammatory [10], anticancer [11,12], antibacterial [13,14], antifungal [15] and anti-HIV [16] and effective animal growth stimulators [17]. Furthermore, many of the benzothiazole derivatives and their metal complexes showed significant antibacterial and antifungal activity [18]. It was found that the action of many drugs increasing when managed as metal complexes than are free ligands [19].

Materials and measurements
2.1.1. Chemicals: All the chemicals and solvents used in this study were purchased from commercial sources (Merck, Fluka, and BDH-Chemical) Companies.  [20]: A mixture of 2-Mercaptobenzothiazole (0.0119 moles, 2 gram) and (8 ml) of hydrazine hydrate H 2 O (80%) was refluxed for 4 hours. The mixture cooled at room temperature, then (5 ml) of ethanol was added. The separated precipitate was filtered and washed with cold water. The green crystals obtained, P. yield 92%, M.P. (202 ℃).

Synthesis of ester derivatives [M2-M7]:
A mixture of (1 mole) of various carboxylic acids dissolved in (5 ml) of absolute ethanol and (2.5 ml) of the concentrated sulfuric acid, was refluxed for 4 hours. After the reaction was completed it neutralized by addition of bicarbonate, then (5 ml) of ether was added until the precipitate formed. The precipitate was filtered and dried.

Antimicrobial Activity test:
The synthesized derivatives [M2, M6, M8, and M12] have been screened in vitro for their antibacterial activity against gram positive bacteria (Staphylococcus aureus) and gram negative bacteria (Escherichia coli) using the disk diffusion method [21] and DMSO as a solvent. The bacterial strains incubated at 37 0C for 24 hours. A standard 6mm diameter sterilizing filter paper impregnates with the above compounds were placed on agar with the tested microorganisms. The concentration of the tested compounds used was: 50, 100, 150, and 200 µL. The inhibition zone was measured in mm. The obtained results are listed in Tables 2a and 2b.

Result and Discussion:
The present work included the synthesis of new benzothiazole hydrazide derivatives. 2hydrazinobenzothiazole prepared from the reaction of 2-mercabtobenzothiazole (MBT) with hydrazine hydrate under refluxing conditions. The synthesis of the desire compounds was accomplished according to the representation in scheme 1.  figure 1 shown bands at 3342asym, 3232sym cm-1 for ʋ (NH2 str.) [23] and absorptions at 3101 which characterized for ʋ (NH str.), strong absorption at 1590 cm-1 for ν (N-H bending), absorption at 1622 cm-1 was due to ν (C=N str.). The sharp bands at 1417 cm-1 due to the ʋ (C=C str.), stretching band at 3062 cm-1 refer to ν (C-H aromatic), and 711 cm-1 for ν (C-S) [24].       (10)(11)(12)(13)(14)(15) were showed disappearance band of (C=O) carbonyl group of ester and appearance a new stratching band for (C=O) of amid group, appearance bands for (NHNH str.) group at about ( 31100-3200) Cm -1 Other bands shown in Table ( (150 and 200 µL), as compared to compounds (M2 and M6). The professional antibacterial activity of compounds M8 and M12 we can attribute may be to the presence of benzothiazole fragment in the structure of these compounds. Eventually, we can conclude that the compounds with benzothiazole hydrazide groups (M8 and M12) can inhibit the growth of the tested bacterial more than the compounds (M2 and M6).