Ralph R. Pfeiffer

Solid-state investigation of the tautomerism of acetohexamide

Polymorphism of the anti-diabetic drug acetohexamide has been investigated by numerous techniques. On the basis of Fourier-transform infrared (FT-IR) data, one of the most common forms, form A, has been proposed to exist in the enol-tautomeric state, whereas form B has been proposed to be in the keto-tautomeric state. The following article examines the solid-state tautomerism of acetohexamide using the techniques of X-ray crystallography and 13 C solid-state nuclear magnetic resonance (NMR) spectroscopy. In the NMR spectra, resonances associated with the acetyl carbonyl and amide carbonyl groups are well resolved. By comparison of the spectra of acetohexamide with those of the related compounds chlorpropamide and tolbutamide, whose crystallographic structures have been determined, it is firmly established that both of the acetohexamide polymorphic forms are in the keto-form. The crystal structure of acetohexamide form A was solved and is reported herein. The structure not only shows the keto-tautomeric state of form A, but also confirms the NMR resonance assignments.

Solid-State Chemistry and Crystal Structure of Cefaclor Dihydrate

Cefaclor [7-(D-2-amino-2-phenylacetamido)-3-chloro-3-cepham-4-carboxylic acid] crystallizes as the dihydrate. Crystals belong to space group P21, with a = 10.626(3), b = 7.1288(9), c = 14.124(3), and β = 121.6(2). The structure was solved using direct methods and refined to an R of 0.0535. The bond lengths, angles, and conformation determined are as expected for cephalosporins. The two water molecules are held in the crystal differently. The 13C solid-state NMR spectrum of cefaclor dihydrate is also reported and is consistent with its crystal structure.

Stable Antibiotic Sensitivity Disks

Two methods of preparing sensitivity disks were compared for their effect on disk stability at 25 and 37 C. One method consisted of applying a solution of the antibiotic to blank disks by the conventional procedure; the second method consisted of applying the antibiotic to the disks as a suspension of crystals. Of the four β-lactam antibiotics that were studied, disks made with suspended crystals were substantially more stable than corresponding disks made by the conventional method. The increased stability is related to the greater chemical stability of the antibiotics in the crystalline versus the amorphous state. Images

The solid-state decarboxylation of the diammonium salt of moxalactam

This paper reports studies of the solid-state chemistry of the diammonium salt of moxalactam. The methods employed include X-ray crystallography, molecular mechanics calculations, thermogravimetric analysis, and high-pressure liquid chromatography. The crystal structure shows that the malonic acid amide functionality in crystals of the diammonium salt is not planar. If the common decarboxylation mechanism is operating, then considerable rotation would be required for this functionality to attain coplanarity. Simultaneous HPLC and thermogravimetric analysis studies indicate that the decarboxylation of the diammonium salt of moxalactam is preceded by desolvation. Molecular mechanics calculations indicate that the barrier to rotation of the malonic acid amide functionality is relatively small in the dehydrated crystals, perhaps explaining the facile decarboxylation of this antibiotic. Alternatively, the amorphous desolvated crystals may allow enough molecular freedom for the malonic acid amide functionality to attain coplanarity and decarboxylate.