Synthesis and Biological activity of 1,3-Thiazolylidenehydrazinylidene ethylpyridiniumbromide monohydrate, 1,3- Thiazolylidenehydraziniumbromide and 1,3-Thiazolylidenehydrazine derivatives

3357 | P a g e F e b r u a r y 0 6 , 2 0 1 5 Synthesis and Biological activity of 1,3-Thiazolylidenehydrazinylidene ethylpyridiniumbromide monohydrate, 1,3Thiazolylidenehydraziniumbromide and 1,3-Thiazolylidenehydrazine derivatives Alaa A. Hassan, Shaaban K. Mohamed, Nasr K. Mohamed*, Kamal M. A. El-Shaieb, Ahmed T. Abdel-Aziz and Marwa Rageh Abdel Rahman a Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt. b Chemistry and Environment Division, Manchester Metropolitan University, Manchester, MI5GD. England. shaabankamel@yahoo.com c Botany Department, Faculty of Science, Sohag University, 82524 Sohag, Egypt ABSTRACT 1,3-Thiazolylidenehydrazinylidene ethylpyridinium bromide monohydrate, 1,3-thiazolylidenehydrazinium bromide and 1,3thiazolylidenehydrazine derivatives were synthesized by heterocyclization of 2-(1-substituted ethylidene)hydrazinecarbothioamides, characterized and screened for their anti-bacterial activities. 3h showed the highest inhibitory effect against all types of bacterial compared to Moxifloxacin. The structures of synthesized compounds were established by spectroscopic (IR, 1 H, 13 C-NMR, Mass) and X-ray analyses.


INTRODUCTION
Compounds possessing Schiff bases are well known for their pharmacological properties as antifungal, anti -cancer and anti-viral agents [1,2].
A NBS-mediated sequential one-pot synthesis of multi-functionalized thiazoles from 1,3-dicarbonyl compounds and mercaptonitrile salts has been developed under mild conditions [7].
The most frequently used synthetic method of generating thiazoles is the Hantzsch process [25], in which α-haloketone is condensed with thioamides. Several methods for the synthesis of tri -substituted thiazoles have been reported [26][27][28][29].
In view of these, it was thought of interest to combine both pharmacophoric moieties 1,3 -thiazole and aromatic compounds (with donating and withdrawing groups) as well as heterocyclic ring (such as pyridine).
A series of substituted 1,3-thiazole derivatives were synthesized and evaluated for their antibacterial activity.
A detailed interpretation of IR bands of 3a is discussed. The IR spectrum of 3a shows a broad band at 3361cm -1 which can be attributed to NH. The (N-N) stretching band in thiazole derivative 3a observed at 1567 cm -1 . The IR of 3a revealed strong band at 1619 cm -1 due to (C=N), the (C-S-C) band was observed at 767 cm -1 [6]. A broad band at 3448 due to the OH of H2O molecule.
The 1 H NMR of 3a chosen as prototype showed that the pyridine-nitrogen still had a proton and pyr-NH resonance at 9.17 ppm, four proton multiplets at 8.20-8.28 due to pyridine-CH, two singlets at 2.32 and 6.42 because the proton of CH3 and thiazole-CH, respectively. A broad signal at 1.6 ppm due to OH of one molecule of H2O. Multiplets at 7.12-7.78 accounting for ten aromatic protons. The molecular structure of 3a was established by single crystal X-ray analysis ( Fig. 1) [35]. The dihedral angle between S1/N1C1-C3 thiazolylidene and N4/C18-C22 pyridinium rings is 14.73 C(3)o while that between the phenyl groups C4 -C9 and C10-C15 and the mean plane of the thiazolylidene ring are 34.69 (13)     H NMR spectrum of 3c, two broad signals at 9.51 and 9.20 ppm due to phenolic-OH, and hydrazinium-NH respectively. In the 13 C NMR spectrum of 3c signals at δC= 157.10, 168.53 and 148.79 ppm were assigned to acyclic C=N, thiazole-C2 and thiazole-C4, respectively. The following additional remarks are necessary: The 1 H NMR spectrum of 3c shows the presence of one singlet at δH= 2.31ppm due to CH3, multiplets at 6.84-7.77 due to aromatic protons. The 13 C N MR shows the CH3 group at 14.15 and thiazole-CH at 102.83 ppm.

Fig. 3. Single crystal x-ray structure of 3c
Substitution the p-hydrogen atom of benzene ring attached to thiazole-C4 by bromide afforded the title compound 3d. For further elucidation the structure of 3d, the single crystal X-ray diffraction has carried out and showed that the bromophenyl, phenyl and phenol rings make dihedral angles of 46.5 (1), 66.78 (8) and 15.4 (2), respectively, with the mean squares plane of the thiazolidene ring. In the crystal, the lattice water molecule is hydrogen bonded to the phenol group and makes a weaker O-H···N connection (Fig. 4) [38].

Fig. 4 Cr ystal structure of 3d
The structures of the third type of the products containing compounds 3e-h were assigned using spectroscopic tools such as IR, NMR ( 1 H-, 13 C) and mass spectrometry as well as single crystal X-ray analyses.

Conclusion
In summary, we have described the synthesis for four types of thi azolylidenhydrazine derivatives via heterocyclization of 2-(1-substituted ethylidene)hydrazinecarbothio-amides by the reaction with 1-aryl-2-bromoethanones. The first type of products is substituted 1,3-thiazolylidene-hydrazonylidene ethylpyridinium bromide monohydrate, whereas substituted 1,3thiazolylidenehydrazinium bromide is the second type of products. The third, is the hemihydrate of 1,3 -thiazolylidene hydrazine derivatives in addition to the derivatives of 1,3 -thiazolylidene hydrazine as the fourth type. Among all types of 1,3-thiazolylidene hydrazines, 3h showed the highest inhibitory effect against all gram positive and gram negative bacterial strains compared to the standard broad spectrum antibiotic Moxifloxacin.

Experimental
Melting points were determined using open glass capillaries on a Gallenkamp melting point apparatus (Weiss -Gallenkamp, loughborough, UK) and are uncorrected. Infrared spectra (υ/cm -1 ) were recorded from potassium bromide disks with a Shimadzu 408 (Shimadzu corporation, Kyoto, Japan).

Anti-bacterial Activity
The synthesized compounds 3a-h were dissolved in DMSO. In order to ensure that the solvent had no effect on bacterial growth or enzymatic activity, negative control tests were performed using DMSO at the same concentrations.
The inhibitory effect of tested compounds 3a-h on the in vitro growth of four different types of bacteria Bacillus cereus and Micrococcus lutues as gram positive bacteria (+ve) and Psedomonas aureginosa and Serratia marcescens as gram negative bacteria (-ve) was evaluated using agar diffusion method (cup and plate method) [45 -48]. All plates were incubated at 37±0.5 ºC for 24 h. The inhibition zone of active compounds was measur ed in cm scale. The results shown in table 1 revealed that compounds 3h and 3f showed the highest inhibitory effect against the two types of bacteria at the three used concentrations, while compounds 3d and 3e, showed moderate activity compared to the standard Moxifloxacin as a broad spectrum antibiotic. Compound 3h exhibited the highest inhibitory effect against the gram positive Bacillus cereus at high concentration while 3c showed high inhibition zone against the gram positive bacteria Micrococcus lutues at low concentration. On the other hand, compounds 3a-c, 3e and 3g showed no bactericidal activity against the gram negative bacterial Psedomonas aureginosa (table 1). F e b r u a r y 0 6 , 2 0 1 5