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triphenylphosphonium chloride in 15 ml of MeOH. After 2 hr of stirring at ambient temp, the mixt was poured into 300 ml of HoO. H20 was decanted from the yellow solid which was digested in 100 ml of hot HoO. After 2 digests, the yellow solid was collected by filtration and recrystd from EtOH-H>0 to give 1.75 g (91%) of light yellow needles, mp 115-116°: lit.26 mp 116°, prepd by an alternate route.4-(3-Methylphenethyl)pyridine ( 45) p-Toluenesulfonate.-A mixt of 2.0 g (10.3 mmoles) of 12 as the free base and 50 mg of 10% Pd/C was reduced as described for 14. After filtration of the catalyst and evapn of the solvent, 2.0 g (10.4 mmoles) of TsOH in 100 ml of Et20 was added to the residue. The salt was collected and recrvstd twice from EtOAc; yield, 3.46 g (02%), mp 112-113°. Ami (CnH»NO»8) C, , N.' 4-(3-Methylphenethyl)pyridinium Methiodide (46).-A mixt of 6.14 g (31 mmoles) of 45 and 10 ml of Mel was heated on a steam bath for 30 sec when it solidified. The solid was heated 5 min more, than recrystd from MeoCO-petr ether (bp 65-110°)-MeOH: vield, 8.37 g (81% ), mp 166-167°. Anal. (CisHisIN) C, , N.Preparation of Enzyme and Assay Methods.-The enzyme prepn was a modification of the method of Potter, et al.,li used for rat brain. A mixt of 2.0 g of rabbit brain Me2CO powder and 40 ml of ice-cold 0.1 mM Versene was homogenized in a pre-(26) G. Drefahl and H. Luckert, J. Prakt. Chem., 9, 302 (1959), Fuller, Mills, and Marsh cooled head of a Waring blender for 2 min. After the addition of 50 gl of 1

Molecular orbital calculations by the CNDO/2 method are used to study the molecular and electronic details involved in the initial phases of the opening of the beta-lactam ring of a model cephalosporin structure, 7-amino-3-acetoxymethyl-3-cephem. The effect of a simple nucleophile, OH-, approaching the carbonyl carbon center of the beta-lactam ring is monitored by following the charge redistributions that occur in the bicyclic system and in the 3 side chain. A migration of electron density to the ester oxygen of the CH2OAc group is observed with concomitant weakening of the CH2-OAc bond. The results are discussed in relation to the mechanism of acylation of bacterial cell wall enzymes by beta-lactam antibiotics and in relation to the hydrolysis of these molecules. The results indicate that the ability of the 3' substituent of cephalosporins to stabilize electron density transferred to it, i.e., the leavability of the 3' moiety, can be an important factor in activating the beta-lactam toward nucleophilic attack.

2957Brief illustrative experimental procedures serve to demonstrate the utility of these methods. First, treatment of 35 mmol of 5 with 50 mmol of LDA in 50 mL of THF for 2 h at 0 OC and hydrolytic workup gave a 96% yield of a 45:55 mixture of the cis and trans isomers of diphenyl-l-propenylamine (I 1). Although stoichiometric amounts of LDA are employed in this case, such isomerizations can be effected by catalytic amounts of LDA as well. Second, treatment of 20 mmol of 5 with 22 mmol of n-BuLi in 100 mL of THF at 0 OC for 1 h gave a deep red solution; then, 20 mmol of PhCHzCl were added and al-(6) A number of allylic diphenylamines, such as CH&H= CHCHPNPhl and PhC€h=CHCH2NPh2, have been prepared in thie manner. Eiech, J. J.; Chiu, C. S.; Shah, J. H. Unpublished studies.lowed to react for 6 h at 25 OC; hydrolytic workup and column chromatography of the dried and evaporated organic layer on silica gel (hexane:CHzClz = 8 2 as eluent) gave, separately, 4-phenylbutanal (75%) and recovered diphenylamine (95%). Third, treatment of 20 mmol of 5 with 22 mmol of n-BuLi in 100 mL of THF at 0 "C for 3 h and the subsequent addition of 20 mmol of benzophenone gave upon the usual hydrolytic workup a crude product that was recrystallized from ethanol to yield 65% of 2-(diphenylamino)-5,5-diphenyltetrahydrofuran, mp 124-125 OC. Treating this with dilute, aqueous HC1 eliminates diphenylamine and forms 2,2-diphenyl-2,3-dihydrofuran.Summary: Oxidation of synthetic manganese(II1) porphyrins attached to steroidal substrates at C(17) (cf. 2 and 3) gives rise to hydrogen atom abstraction at C(9) and/or C(12), thereby leading to hydroxyl incorporation at these sites. The use of more robust metalloporphyrins (cf. 9) results in substantial increases in the yields of hydroxylated 5cu-androstanes.