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SYNTHESIS, STRUCTURE AND BIOACTIVITY OF SOME THIAZAHETEROCYCLES

Saeed, Sadaf (2008) SYNTHESIS, STRUCTURE AND BIOACTIVITY OF SOME THIAZAHETEROCYCLES. PhD thesis, Quaid-i-Azam University, Islamabad.

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Abstract

The work described in this thesis consists of synthesis. structure and bioactivity of some new heterocyclic compounds. The compounds included in this thesis are seven membered ring compounds, which contain heteroatoms nitrogen, oxygen and sulphur. Few six membered ring compounds were also synthesized which contain nitrogen and oxygen atoms. The seven membered compounds include different 3-substituted phenyl- 5,6-dihydro-7 H-1,4,2- oxathiazepin-7-one (78-97), 4,I,3-benzoxathiazepin-5-one (123-137), pyrido[2,3e][I,4,2]oxathiazepin-5-one (161-173), 5,6-dihydro-7H-1,,4,2-oxathiazepin-7-one(188-192), 6-[(acetyloxy)amino]-3-(4-substitutedphenyl)-5,5-dimethyl-5,6-dihydro-7 H-1,4,2 oxathiazepin-7-one (197-198). These compounds were prepared by treating hydroximinoyl chlorides with different mercapto acids. These acids included 3-mercaptopropanoic acid, 2mercaptosalicylic acid. 2-mercaptonicotinic acid. cysteine and penicilamine. The first step in the synthesis of these compounds was the formation of oximes by treating aldehydes with hydroxylamine hydrochloride. The variety of aldehydes was selected for this work with aromatic and heteroaromatic nuclei. The second step was the conversion of these oximes to the hydroximinoyl chlorides. This step was carried out by treating oximes with different chlorinating agents, NCS and BTMAICI4. These hydroximinoyl chlorides in the next step were treated with different mercapto acids to give oxime acids. The reaction was carried out in the presence of base, triethyl amine. The last step was cyclization and carried out by adding DCC as cyclizing agent to the reaction mixture. The chemical reactivity of these compounds was investigated by carrying out different reactions. Thus oxathiazepines were treated with phosphorus pentasulphide, primary and secondary amines, LiAlH4 and alcohol to get thiones. amides, alcohols and esters respectively. It was found that the same ring cleaved product was obtained under both acidic and basic conditions. Ring also cleaved in case of reaction with amine, alcohol and LiAlH4. The synthesis of another class of six membered ring compounds i.e. 1,2,4-oxadiazin-5-one and 6,6-dimethyl-1,2,4-oxadiazin-5-one (217-221) was also carried out by treating amidoximes with chloroacetyl chloride and 2-bromo-2-methylpropanoyl bromide. The amidoximes were prepared by treating hydroximinoyl chloride with different primary and secondary amines which include benzylamine, 2-aminopyridine, 2-chloroaminobenzene, 1-naphthylamine, 4-aminopyridine, cyclopropylamine, dibenzylamine and diisopropylamine. 7,7-dimethyl-3,5-disubstituteddihydro-1H-[1 ,3]thiazolo[3,4-c][1,3]oxazol-l-one(199-201) were also synthesized by the reaction of aldehydes with Penicillamine. The compounds thus formed were characterized by different spectroscopic techniques like UV, IR, 1H, 13C NMR, COSY, HMQC, DNMR and mass spectral analysis. NOE experiments were performed to confirm the stereochemistry of the hydroximinoyl chlorides, oxime acids and amidoximes. These compounds were found to have Z- configuration. Elemental analysis and X-ray crystal analysis was also carried out in many cases. The synthesized compounds after characterization were subjected to biological activity testing; antibacterial, antifungal, antioxidant and antidiabetic activities. Some of the compounds were found to exhibit excellent antibacterial and antifungal activity. The oxime acids proved to be good antioxidants while a few oxathiazepines have also shown good antidiabetic activity.

Item Type:Thesis (PhD)
Subjects:Physical Sciences (f) > Chemistry(f2) > Inorganic Chemistry (f2.4)
ID Code:2597
Deposited By:Mr. Javed Memon
Deposited On:08 Jul 2009 12:13
Last Modified:08 Jul 2009 12:13

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