Primary and secondary alkyl chlorides have been conveniently prepared by the reaction of tri-noctylphosphine with carbon tetrachloride solutions of the corresponding alcohols. This rapid, high yield reaction proceeds with inversion of configuration. By using carbon tetrabromide the method has been extended to the synthesis of alkyl bromides.Canadian Journal of Chemistry, 46, 86 (1968) The formation of ylid 1 (R = C6H5) and trivhenvlvhosvhine dihalide (2) from the inter-[41aciion o i trip~ienylphosphine with carbon tetra-Accordingly, we have found that phosphines halides (eq. [l]) was simultaneously and inde-snloothly convert alcohols to chlorides (eq.[5]). pendently discovered by Rabinowitz and Marcus (1) and Ramirez and co-workers (2). An ionic mechanism iilvolving nucleophilic displacement on halogen has been invoked (3) to account for the formation of these products (eqs.[2] and [3]).Ylids of structure 1 (R = C6Hj) possess considerable syntlietic potential since they provide a route to otherwise difficultly accessible 1,l-dihaloalkenes on reaction with carbonyl compounds (1,2,4). Reagents of the type R3PX2 (R = C6H5 or 12-C4H9) have been demonstrated to perinit the conversion of alcol~ols to alkyl halides to proceed generally without complication of elii1liilation or rearrangement (5, 6); in addition, they convert phenols to aryl ha!ides (6,7) without formation of position isomers.The present study arose out of a consideration that intermediates of structure 3 (or 4) C O L I~~ be trapped by reaction with alcohols to provide 5 (or 6), e.g.The anticipated collapse of 6 to alkyl halide and tertiary phosphine oxide finds ample analogy in a related study (8).[5] R3P + R'OH + CCI4 + R'C1 + R 3 P 0 + HCC13 where R = t1-C8Hl7 or C6H5Using tri-12-octylphosphine (TOP) and primary alcohols, conversions are of the order 90-100 % in favorable cases. Tripl~enylphospl~ine may also be used at longer reaction times.1 Although no attempts at optin~ization have been made, we find that this facile transformation is conveniently accomplished (for chlorides) by adding a slight excess over one inole equivalent of TOP to a solution of alcohol in carbon tetracl~loride as solvent. A vigorous reaction ensues which is con~plete, in the case of primary alcohols, in ca. 5 min. The product is readily isolated by standard methods of distillation and chromatograpl~y (cf. Experimental).Typical results are the formation of i2-C5H1 lC1 (94%), C6H5CH2CI (loo%), rz-C8HI7Cl (93 %), and C6H5CH2CH2C1 (66 %).2 Secondary alcohols also react. Thus, after ca. 5 mill reaction time, sec-butyl chloride and 2-chlorooctane were formed in 60 % and 80 % yields,

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Gupte has developed a much more convenient synthesis: ethyl N-aminocarbamate, made by warming diethy1 carbonate and hYdrazine* is added to phenyl isocyanate, and the product treated with alkali.

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Several brominated androgen derivatives were tested for their ability to inactivate microsomal aromatase from term human placenta. In the experimental protocol, the microsomal homogenate was incubated either with androstenedione or a brominated derivative of androstenedione (16alpha-bromo-6-ketoandrostenedione, 16alpha-bromoandrostenedione, 7alpha-(3'-bromoacetoxypropyl)androstenedione, 6alpha-bromoandrostenedione, or 6beta-bromoandrostenedione) and reduced nicotinamide adenine dinucleotide phosphate in a nitrogen saturated buffer composed of glycerol, ethylenediaminetetraacetic acid, and dithiothreitol in tris(hydroxymethyl)aminomethane hydrochloride (pH 7.4) under nitrogen at 4 degrees C with shaking. After the incubation period, the microsomes were recovered by centrifugation and washed once before determining aromatase specific activity. The brominated androgen derivatives which inactivated aromatase were 7alpha-(3'-bromoacetoxypropyl)androstenedione and 6alpha-bromoandrostenedione. The structures of 6alpha- and 6beta-bromoandrostenedione were unequivocally established by single crystal x-ray diffraction techniques. The extent of the enzyme inactivation by 6alpha-bromoandrostenedione was linearly proportional to the logarithm of its concentration. The evidence that this inactivation occurs at the aromatase active site is that androstenedione, when coincubated with 6alpha-bromoandrostenedione, protected aromatase from this inactivation. Progesterone provided much less protection than androstenedione. Furthermore, both 6alpha- and 6beta-bromoandrostenedione are competitive inhibitors of androstenedione aromatization, as determined by a Lineweaver-Burk plot, and 6alpha-bromoandrostenedione gives the same type I cytochrome P-450 binding spectrum with placental microsomes as androstenedione. These data suggest that 6alpha-bromandrostenedione is effective as an active-site-directed inhibitor of placental microsomal aromatase.