Optical active halides

This is, of course, the Wurtz reaction, and support for such a mechanism involving carbanions (radicals may be involved under some conditions, however) is provided by the observation that in some cases it is possible, with optically active halides, to demonstrate inversion of configuration at the carbon atom undergoing nucleophilic attack. The carbanion, e.g. (61), can also act as a base and promote elimination ... 

Although the tin hydride reductions of alkyl halides seem simple, one must be careful because these reactions occur by a free radical mechanism. This is important, because the carbon radical produced in the reaction can isomerize68,78 and one often obtains two different stereoisomers from the synthesis. Another problem is that chiral centres can be lost in tin hydride reductions when an optically active halide is reduced. One example of this is the reduction of benzyl-6-isocyanopenicillanate with tributyltin deuteride78 (Scheme 14). The amount of isomerization depends on the temperature, the concentration of the tin hydride and the presence of and /-substituents78-82. However, some authors have reported tin hydride reductions where no racemization was observed78. 

Thus. S 2 reactions of optically active halides are accompanied by Inversion of configuration. 

Optically active halides also can be racemized by an SN2 mechanism. A solution of active 2-chlorobutane in 2-propanone containing dissolved lithium chloride becomes racemic. Displacement of the chloride of the halide by chloride ion inverts configuration at the atom undergoing substitution (see Section 8-5). A second substitution regenerates the original enantiomer. Eventually, this back-and-forth process produces equal numbers of the D and l forms the substance then is racemic ... 

Evidence of both types of potential intermediate in reduction by Sml2, the alkyl radical and the ketyl radical 27, has been provided by radical cyclisation reactions. Mechanism 4, which involves an Sjj2 substitution, has been eliminated because optically active halides are completely racemised. The rate of addition of alkyl radicals to ketones is very slow (<102 dm3 mol-1 s-1) the resulting alkoxy radicals (26) are very reactive and could not... 

This means that water can attack this carbocation in the second step with equal probability from either side of the carbon atom. This has no effect on the products of this reaction, because the starting material is not optically active. But what would happen if we started with an optically active halide, such as 2-bromobutane ... 

The racemization of optically active halides in the coupling process may, however, also be a result of the configurational lability of organoiron intermediates. 

The Sn2 mechanism is a one step process involving both the alkyl halide and nucleophile simultaneously. The nucleophile enters as the halide leaves, attacking the carbon from the side opposite to that from which the halide departs. The reaction is bimolecular this means the reaction rate depends on the concentrations of both the alkyl halide and the nucleophile. The reaction involving optically active halides occurs with inversion of configuration. 

Stereochemistry SN2 reactions involving optically active halides produce optically active products but with inversion of configuration of the chiral carbon atom bearing the halogen attack by the nucleophile occurs on the opposite side from that the halide is leaving. SN1 reactions proceed by a carbocation intermediate that can be attacked by the nucleophile from either side a racemic mixture results. 

Such reactions should proceed with inversion of configuration if an optically active halide is used. However, a claim to have established inversion in one case has been shown to be erroneous14 and definitive proof is as yet lacking. 

In the only reported examples (107) of the Michaelis-Arbuzov reaction with optically active halides (2-halooctane and 1-halophenyl-ethane), results were inconclusive. The halides underwent extensive racemization in preference to furnishing the expected phosphonate. The stereochemical nature of the attack by phosphite on alkyl halides could perhaps be clarified by the use of optically active primary deutero-halides (RC DHX), wherein steric hindrance is at a minimum, and one could more easily obtain phosphonate products. No experiments of this type have been reported. 

The use of the same optically active halide 97 demonstrated predominant inversion of configuration in its reaction with ammonia. It is highly likely that for most simple phos-phono- and phosphino-thioic halides a reaction with a secondary amine proceeds with inversion of phosphorus configuration on the other hand, the stereochemical outcome of a displacement reaction which involves a halide of the type (R NH)R P(S)C1 and an amine depends on the basicity of the attacking amine and would appear to occur through an initial elimination of HCl. Such differences in mechanisms will again be referred to later. 

Although Sn2 reactions are stereospecific and proceed with inversion of configuration at carbon, the situation is not as clear-cut for SnI. When the leaving group departs from a chirality center of an optically active halide, the positively charged carbon that results is 577 -hybridized and cannot be a chirahty center. The three bonds to that carbon define a plane of symmetry. 

Reduction of ketones with Grignard reagents prepared from certain optically active halides yields optically active secondary alcohols. Mosher and his associates (Burrows et al., 1960 Birtwistle et al., 1964 and references therein) have studied both the qualitative and quantitative aspects of such asymmetric reductions. 

ABSTRACT The gas-solid halogenation and hydrohalogenation using micro-crystalline cyclodextrin complexes are found to be efficient for production of the optical active halides of ethyl trans-cinnamate in moderate optical yields On exposure to HBr at 2QOC for 15-20 hr, the cinnamate in solid a- and S-cyclodextrin complexes yields ethyl R-(+)-3-bromo-3-phenylpropanoate in 46% e.e., and S-(-)-enantiomer in 31% e.e., respectively. No addition nor substitution products are obtained with HCl vapor at 0-50°C for 15-65 hr. Bromination of the B-cyclodextrin complex results in the formation of optical active ethyl erz/t/zrc>-2,3-dibromo-3-phenylpropanoate, while chlorination gives the optical active mixture of trans and cis addition products, ethyl erythro- and threo-2,3-di-chloro-3-phenylpropanoates in 60-80% yields. Mechanism of chiral induction in the present gas-solid reaction has been proposed on the basis of the crystal structure of the complex. 

Concerted reactions are usually stereospecific, and this becomes evident when a suitably substituted molecule is employed in the reaction as the starting material. The classical Sn 2 reaction is a good example of a thoroughly concerted stereospecific chemical process, reaction (3.1). Non-concerted reactions are not usually stereospecific simply because the stereochemical integrity may be lost in the formation of the reactive intermediate. A suitable example is given by the Sn 1 hydrolysis of an optically active halide, reaction (3.2). 

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