Hydrogen-nuclear magnetic resonance titrations

The results of degradative studies, together with data provided by infrared spectra, nuclear magnetic resonance spectra, and electrometric titrations, led Abraham and Newton s to propose the structure VII for cephalosporin C. An X-ray crystallographic study by Hodgkin and Maslen led to the same structure and showed that the hydrogen atoms on the /S-lactam ring are cis, as they are in the penicillins . 

The effectiveness of these chiral host compounds has been shown in highly enantioselective [2+2]-and [4+4]-cycloadditions of prochiral lactams. Prochiral lactams such as 2-quinolone derivatives are expected to coordinate to lactam 21 with its NH-group as the hydrogen donor and the carbonyl group as the hydrogen acceptor, as depicted in Scheme 9. In this complex, any intra- or intermolecular attack at the quinolone double bond can occur exclusively from the Re-face relative to carbon atom C3. The other face of the molecule is shielded by the bulky tetrahydronaphthalene unit. Following H nuclear magnetic resonance ( H-NMR) titration experiments, the association constant of 2-quinolone 22 and host 21 in toluene was determined as IQ = 500 AT at 30°C, and a 1 1 complex stoichiometry was proved. Because the complex formation was found to be exothermic, an enhanced association was expected at lower temperatures. 

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