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Title of Thesis

Sheikh Shaukat Ali
Institute/University/Department Details
Institute of Chemistry University of the Punjab, Lahore
Number of Pages
Keywords (Extracted from title, table of contents and abstract of thesis)
ethyl acetoacetate, Ÿ-keto compounds, amino compounds, hydroxylamine hydrochloride, ethyl acetoacetate, cyclocondensation products, aldehydes, ketones, hexamethylenetetramine

Hydroxylamine hydrochloride is known to react with ethyl acetoacetate to yield different condensation and cyclocondensation products, the formation of which depends upon the reaction conditions. This reaction has been studied by various research workers. However, there are certain aspects of this reaction which have been reported to yield quite conflicting results, and the reports of the past researchers portrait quite confusing situation as to the nature of products obtained in this reaction. Therefore, the reaction of ethyl acetoacetate and hydroxylamine hydrochloride has been thoroughly. investigated particularly in the aqueous medium. Effects of variations of parameters like molar concentration, pH changes and temperature variation, have been studied. Optimum conditions for the formation of 4-isopropylidene-3-methylisoxazol-5-one. 3-methylisoxazol-5-one anhydride and 2,2-di(3-methylisoxazol-5-one-4-yl)propane have been determined. The maximum yields of these compounds , were 67, 58 and 63 % respectively. A plausible reaction scheme for the formation of these compounds has also been suggested.

Hydroxylamine ,hydrochloride reacts with ethyl acetoacetate in presence of aliphatic and aromatic aldehydes and ketones to yield 4-substituted 3-methylisoxazol-5-ones. These isoxazolone derivatives are an important class of heterocyclic compounds which find many uses in industry. agriculture. and medicine. These derivatives have also been use as analytical reagents . In ,view of the importance of , these' compounds, the reactions of ethyl acetoacetate and hydroxylamine hydrochloride in presence of various aliphat- ic/aromatic aldehydes, and ketones. leading, to the formation of 4-substituted alkylidene/arylidene-3-methylisoxazol-5-ones have been thoroughly investigated. The present work describes the synthesis of -several 4-alkylidene/arylidene-3-methylisoxazol-5-ones and 4,4€™-alkylidene/arylidenne-bis (3-methylisoxazol-5-one)s. the comparison of previous methods on the subject reveals that the present method offers simple route for the Syntheses of arylidene/alky1idene 3-methylisoxazo1-5-ones in yields varying from 49-96 %. A cursery view of the different routes for their formation has also been presented. The following isoxazolones have been synthesized:

4-Benzylidene-3-methylisoxazol-5-one(73 %) 4-Salicylidene-3-methylisoxazol-5-one (87 %) 4-(3-Hydroxylbenzylidene)-3-methylisoxazol-5-one (86 %) 4-(4-Hydroxylbenzylidene)-3-methylisoxazol-5-one(72%) 4-(2-Methoxybenzaldehyde)-3-methylisoxazol-5-one(77%) 4-Anisalidene-3-methylisoxazol-5-one (80 %) 4-Vanillidene-3-methylisoxazol-5-one(96%) 4-(3,4-Dimethoxybenzylidene)-3-methylisoxazol-5-one(79%) 4-(P-Dimethylaminobenzylidene)-3-methylisoxazol-5- one (75 %) 4-Cinnamyl1dene-3-methylisoxazol-5-one (73 %) 4-Isopropylidene-3-methylisoxazol-5-one(41%) 4-4€™-Benzylidene-bis(3-methylisoxazol-5-one) (49 %) Di(3-methylisoxazol-5-one-4-yl)methane(86%) l,l-Di(3-methylisoxazol-5-one-4-yl)ethane(58%) l,l-Di(3-methylisoxazol-5-one-4-yl)propane(77%) 2,2-Di(3-methylisoxazol-5-one-4-yl)propane(64 %)

It has been reported that 3,5-disubstituted pyrazole and pyrazolone .derivatives possess hypoglycemic and anti-microbial activities. They are also used as corrosion inhibitors and antifogging agents in photographic systems, and their metal complexes are useful chemical reagents. Therefore, in view of the importance of these products, the. reactions of semicarbazide hydrochloride and hydrazine monohydrate with ethyl acetoacetate, acetylacetone, benzoylacetone and dibenzoylmethane leading to the formation of pyrazole and pyrazolone derivatives have been intensively studied in the aqueous as well as in the ,non-aqueous medium under various sets of conditions. This has resulted in the development of simple and convenient methods for the synthesis of pure ethyl acetoacetate semicarbazone,3-methyl-pyrazol-5-one-1-carboxamide, 3-methylpyrazol-5-one, hydra zine-1,2-diamide, 3,5-dimethylpyrazol-1-carboxamide, 3,5-dimethypyrazole, 3-phenyl-5-methylpyrazole-1-carboxamide,3-phenyl-5-methylpyrazole and 3,5-diphenylpyrazole. The yields of the sufficiently pure compounds were 81, 56, 93, 37, 88, 71, 68, 99 and 78 % respectively. It has been suggested that the reaction of semicarbazide hydrochloride with β-diketo compounds proceeds through four stages. A reaction scheme has been proposed to explain the formation of different products.

Hexamine reacts with β-diketo compounds in presence of ammonia to form dihydropyridine derivatives, which find utility in medicine. These derivatives are quite , expensive. Their present methods of preparation are quite lengthy and involve different steps. In order to use hexamine as a dual source of formaldehyde and ammonia, reactions of ,hexamethylenetetramine with active methylene compounds like ethyl acetoacetate, acetylacetone, dimedone and dibenzoylmethane have been thoroughly investigated. These investigations have led to the successful development of simple, convenient and economical methods for the synthesis of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxy-late,3,5-diacetyl-l,4-dihydro-2,6-dimethylpyridine,and 1,8-dioxo-3,3,6,6-tetramethyl-l,2,3,4,5,6,7,8,9,10-decahydroa-cridin in 75, 59 yield 46 % yields respectively. The conditions for the preparation of bis (2,6-dioxo-4,4-dimethylcy-clohexyl)methane (49 %), α,α,γ,γ-tetrabenzoylpropane and (58 %) have also been determined.

The structures of various compounds obtained have been established usually by combustion analysis, infrared, nuclear magnetic resonance and mass spectra. In case of dihydropyridine derivatives, their tautomeric nature has been established by spectroscopic and chromatographic analysis

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
73.9 KB
2 1 Introduction 1
173.19 KB
  1.1 Introduction 01
  1.2 Introduction to present work 25
3 2 Experimental 32
282.12 KB
  2.1 Material and methods 32
  2.2 Reaction of hydroxylamine hydrochloride with ethyl acetoacetate 35
  2.3 Reactions of hydroxylamine hydrochloride with ethyl acetoacetate 8in presence of aldehydes and ketones 47
  2.4 Reactions of hydrazine and its derivatives with β-Keto ester and β-Diketones 60
  2.5 Reactions of hexamethylenetetramine with β-Keto ester and β-Diketones 77
4 3 Results and discussion 82
273.67 KB
  3.1 Reaction of hydroxylamine hydrochloride with ethyl acetoacetate 82
  3.2 Reactions of hydroxylamine hydrochloride with ethyl acetoacetate in presence of aldehydes and ketones 97
  3.3 Reactions of hydrazine and its derivatives with β-Keto ester and β-Diketones 104
  3.4 Reactions of hexamethylenetetramine 118
5 4 Spectroscopic and chromatographic evidence for the formation of tautomeric dihydropyridines in the reaction of β-Diketo compounds and hexamethylenetetramine
147.82 KB
  4.1 Introduction 136
  4.2 Experimental 137
  4.3 Results and discussion 139
  5 References 161
  5.1 Publications 169