Acetolysis halides

The systematic study of nucleophilic substitutions of steroid alcohols and halides, pursued by Shoppee since 1946 [47], has yielded many examples of reactions which proceed with stereochemical inversion (Walden Inversion) [48] at the reaction centre. Acetolysis of the epimeric 3-chloro-5a- [4 ] and 3-chloro-5/ -cholestanes [4g] with potassium acetate in acetic acid gives 3-acetoxy derivatives of inverted configurations (Fig. 14) cholestenes, derived by elimination reactions, are... 

The apparent contradiction to symbiosis during acetolysis of hex-5-enyl derivatives (95) is inferred from the observation that more double-bond participation products arise from the arenesulfonates than the softer halides. Pearson (96) argues that the solvolysis may be more complex than a simple Sfsj2 type displacement and as such there is no reason for symbiosis to be the dominant factor. 

Nucleophilic substitution reactions that occur under conditions of amine deamination often differ significantly in stereochemistry, compared with that seen in halide or arenesulfonate solvolysis. The results of four key substrates are summarized in Table 5.13. It can be seen (entry 1) that displacement of nitrogen on the 1-butyldiazonium ion is much less stereospecific than the 100% inversion observed on acetolysis of the corresponding brosylate. Similarly, the secondary system (entry 2) affords 2-butyl acetate with only 28% inversion of configuration. Furthermore, a crossover to net retention of configuration is observed as the alkyl group becomes better able to stabilize a carbonium ion. The small net retention (10%) observed in deamination of 1-phenylethylamine increases to 28% retention in the tertiary benzylic system 2-phenyl-2-butylamine. 

Solvolysis of the inseparable mixture of (203) and its allylically related isomer has previously been shown to give the acetates (205), (206), and (207) (R = Ac), (206) predominating. It is now shown that solvolysis of (204) (also a mixture of isomers) likewise gives mainly or exclusively (206) (R = H, Me, or Ac) plus some (205) and (207). The dihalogeno-analogue (208) on acetolysis in the presence of Ag" ions yields (211) in 50% yield. Presumably loss of the first halide leads to (209), which is an analogue of (206). Loss of the second halide ion yields a bishomotropylium ion (210) which captures acetate ion to give (211). ... 

The discussion and experiments presented below illustrate methods of studying chemical kinetics and determining the effects of structure on reactivity, as exemplified by the solvolysis of tertiary alkyl halides. The term "solvolysis" describes a substitution reaction in which the solvent, HOS, functions as the nucleophile (Eq. 14.30). In principle, solvolyses may be performed in any nucleophilic solvent such as water (hydrolysis), alcohols (alcoholysis), and carboxylic acids (for example, acetolysis with acetic acid). However, a practical limitation in choosing a solvent is the solubility of the substrate in the solvent because the reaction mixture must be homogeneous if it is not, surface effects at the interface of the phases will make the kinetic results difficult to interpret and probably nonreproducible as well. In the experiment described here, you will explore solvolyses in mixtures of 2-propanol and water. 

A useful halide was encountered by Hudson and co-workers 29) in the partial acetolysis of methyl tri-0-acetyl-/8-D-arabinopyranoside and was shown to have the structure R—CH(OMe)Cl. It was obtainable in two forms and its halogen was replaceable by methoxyl and acetoxyl groups. Other and more general methods for preparing these halides were devised by Wolfrom and co-workers 84) and the products were utilized in the preparation of acetals and thioacetals, as shown below 85),... 

Bridgehead olefins (834 n = 3 or 4) are formed in the solvolysis of the dibromo-propellanes (833 n = 3 or 4) by loss of halide anion, electrocyclic cleavage of the cyclopropane ring, and solvent capture/ The products isolated depend upon the precise reaction conditions in the case of (833 n = 3) acetolysis affords (835 53%) and (836 18 %) provided that water is not present. The details of the mechanism of the Ag" "-assisted solvolysis of (833 n = 4) have been elucidated with the aid of labelling. " ... 

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