A general method is developed using *H and 13C NMR chemical shifts to determine unambiguously the predominant tautomeric form of many known aryl cyclic amidines and guanidines, 2-aminoimidazoles, 2-imino(amino)thiazines, and related tautomeric systems. In the case of 2-aryliminopyrrolidines, evidence for geometrical isomerism was found in both and 13C NMR experiments. These results support the conclusion that, in all these potentially tautomeric systems under the present studies, the predominant tautomer is in the imino form [ArN=C(NHR)R'] rather than the amino form [ArNHC(=NR)R'].

A series of 1-(substituted phenoxy)-3-(tert-butylamino)-2-propanols in which the ring substituents were 3,4-dihydroxy (6f), 3- and 4-hydroxy (6g and 6h, respectively), 3-hydroxy-4-methylsulfonamido (6i), its 3,4-transposed isomer (6j), and 4-methylsulfonylmethyl (6k) was prepared and examined for beta-adrenergic agonist and/or antagonist properties. Two of these compounds, 6f and 6j, were potent beta-adrenoreceptor agonists in in vitro tests that measure a compound's ability to relax guinea pig tracheal smooth muscle and to increase the rate of contraction of guinea pig right atria. Several compounds had a dose-dependent effect. Although they produced potent beta-adrenergic agonist activity at low concentrations, 6g, 6h, and 6j antagonized the effects of a standard beta-adrenoreceptor agonist at higher concentrations. The methylsulfonylmethyl derivative 6k produced beta-adrenergic blocking effects as demonstrated by attenuation of isoproterenol-induced increases in the rate of contraction of an isolated rabbit heart preparation. On the basis of these pharmacological results, coupled with NMR spectral data, it appears that the previous suggestion that aryloxypropanolamines interact with beta-adrenocreceptors as a consequence of their ability to assume an orientation in which the benzene ring the ethanolamine moieties can be superimposed on those of corresponding adrenergic phenylethanolamines is invalid. An alternative "bicyclic" rigid conformation involving two intramolecular hydrogen bonds in the protonated form of the aryloxypropanolamines is suggested to account for the similar beta-adrenoreceptor activity of these compounds and related phenylethanolamines.

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A method for introducing the C-6(7) methoxy group on penicillins and cephalosporins via a route using presumably both carbanion and carbonium ion intermediates is described. Treatment of esters of C-6(7) benzylideneaminopenicillin and -cephalosporin with NaH and MeSSOzMe gave the corresponding C-6(7) methylthio derivatives. Hydrolytic removal of the benzylidene group of the above derivatives followed by treatment with HgClz in methanol afforded benzyl 6-amino-6-methoxypenicillanate and iert-butyl 7-amino-7-methoxydeacetoxycephalosporanate. These compounds were converted to the appropriate penicillin and cephalosporin analogs by acylation and removal of the ester groups. Assignment of a Configuration to the methoxy group is discussed.