18715-92-9

Upstream product

• 5321-32-4 hetacillin potassium 
• 3511-16-8 hetacillin 
• 40439-01-8 hetacillin 

Downstream Products

• 69-53-4 6-epi-ampicillin 
• 217644-25-2 (4S)-2t-((2S)-3,6-dioxo-5c-phenyl-piperazin-2r-yl)-5,5-dimethyl-thiazolidine-4r-carboxylic acid 
• 49841-95-4 6α-((R)-2-amino-2-phenyl-acetylamino)-penicillanic acid 
• 65058-91-5 6α-((R)-2,2-dimethyl-3-nitroso-5-oxo-4-phenyl-imidazolidin-1-yl)-penicillanic acid 
• 49841-97-6 (4S)-2t-((2S)-3,6-dioxo-5c-phenyl-piperazin-2r-yl)-5,5-dimethyl-thiazolidine-4r-carboxylic acid methyl ester 
• 22888-48-8 6β-((R)-2-benzylamino-2-phenyl-acetylamino)-penicillanic acid benzyl ester 
• 21794-95-6 6α-(2-phenyl-acetylamino)-penicillanic acid methyl ester 
• 47294-44-0 6α-(2-phenyl-acetylamino)-penicillanic acid 
• 18715-93-0 6α-((R)-2,2-dimethyl-5-oxo-4-phenyl-imidazolidin-1-yl)-penicillanic acid methyl ester 
• 94595-14-9 2-(3,6-dioxo-5-phenylpiperazine-2-yl)-5,5-dimethylthiazolidine-4-carboxylic acid 

Relevant academic research and scientific papers

Hydrolysis and epimerization kinetics of hetacillin in aqueous solution

Methods were developed for quantitating epimerization to epihetacillin and hydrolysis to ampicillin in the alkaline degradation of hetacillin, and both rates in deuterium oxide at 35° and in water at various temperatures were determined. In each case, plots of log k for the epimerization against pH or pD yielded straight lines with a positive slope, which verified the first-order dependence on the hydroxide ion or deuteroxide ion. The activation energy of the epimerization process was 21.2 kcal/mole. In aqueous solution at high pH, epimerization rather than conversion to ampicillin represents a major pathway of hetacillin degradation, although the β-lactam ring of the hetacillin molecule is highly resistant to attack by the hydroxide ion.

Chemical reactivity of penicillins and cephalosporins. Intramolecular involvement of the acyl-amido side chain

The rate of degradation of 6-epi-ampicillin in acidic, neutral, and alkaline aqueous solutions was followed at 35 °C and an ionic strength of 0.5 mol dm-3 (KCl) by high-performance liquid chromatography (HPLC) and spectrophotometric assays. Pseudo-first-order rate constants were determined in a variety of buffer solutions, and the overall pH-rate profile was obtained by extrapolation to zero buffer concentration. The hydrolysis of 6- epi-ampicillin is subject to acid and hydroxide-ion catalysis and, for a penicillin, an unusual pH-independent reaction. Intramolecular general base- catalyzed hydrolysis by the side chain amido group is proposed to explain the enhanced rate of neutral hydrolysis of 6-epi-ampicillin and cephalosporins. The β-lactam of 6-epi-ampicillin also undergoes intramolecular aminolysis by nucleophilic attack of the 6-α side chain amino group to give a stable piperazine-2,5-dione derivative. The low effective molarity for intramolecular aminolysis of only 40 M is partly attributed to the unfavorable trans to cis isomerization about the 6-amide side chain required for ring closure. Theoretical calculations show that the intramolecular aminolysis of 6-epi-ampicillin nucleophilic attack occurs from the α-face of the β-lactam ring with an activation energy of 14.4 kcal/mol.