PART I: SOLID STATE DECARBOXYLATION OF MOXALACTAM AND 2-PHENYLPROPANEDIOIC ACID MODEL COMPOUNDS. PART II: SOLID STATE DESOLVATION OF CEFACLOR AND CEFAZOLIN

HERIBERTO MARTINEZ, Purdue University

Abstract

Part 1. The solid state decarboxylation of the diammonium salt of moxalactam hydrate was studied. During degradation, this compound lost water followed by the simultaneous loss of ammonia and carbon dioxide. The proposed mechanism is postulated to involve a carbanion intermediate. The solid state decarboxylation of several phenylpropanedioic acid model compounds was also studied. The X-ray crystal structures of 2-phenylpropanedioic acid, 4'-methyl-2-phenylpropanedioic acid, 2-methyl-2-phenylpropanedioic acid, 4'-hydroxy-2-phenylpropanedioic acid, 2-phenylpropanedioic acid monosodium salt monohydrate, 2-phenylpropanedioic acid monosodium salt, 2-phenylpropanedioic acid monopotassium salt, 4'-hydroxy-2-phenylpropanedioic acid monosodium salt, 4'-hydroxy-2-phenylpropanedioic acid monopotassium salt, 5-methyl-2-furoic acid and 5-tetradecyloxy-2-furoic acid were determined. The TGA threshold temperature was used as a stability indicator for these acids. This temperature was shown to increase as the electron donating ability of the group in the (alpha)-position or in the 4'-position of the phenyl ring increased. Also, the half salts were shown to be more stable than the free acid. The solvent of crystalization was shown to play an important role in the degradation of the monosodium salt of 2-phenylpropanedioic acid. The desolvation of the 0.5 benzene solvate of 4'-hydroxy-2-phenylpropanedioic acid was studied using DSC. Benzene was shown to be held very loosely in the solvent tunnel. Part II. The crystal structure of the cefaclor dihydrate was determined. The two water molecules were held differently in the crystal lattice. This dihydrate desolvated readily under low relative humidities to form the monohydrate which had a different diffraction pattern. The monohydrate desolvated with no major differences in the powder pattern. The solid state ('13)C NMR and the IR-spectra of the dihydrate and monohydrate were very similar. The crystal structure of cefazolin pentahydrate was determined by X-ray crystallography. This structure was solved originally in a monoclinic space group (P2(,1), Z = 4) and the packing of the molecules was shown to be identical with that reported by Van Meersche for the sodium chloride monohydrate of cefazolin. The water and sodium atoms of the Van Meersche structure were reassigned and the correct assignments are reported. The different forms of cefazolin (monohydrate, sesquihydrate, pentahydrate and amorphous) were analyzed and differentiated by TGA, DSC, x-ray powder diffraction, IR and ('13)C solid state NMR.

Degree

Ph.D.

Subject Area

Analytical chemistry

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