Halides, benzylic, from alcohols

Hydrolysis of alkyl halides is severely limited as a method of synthesizing alcohols, since alcohols are usually more available than the corresponding halides indeed, the best general preparation of halides is from alcohols. The synthesis of benzyl alcohol from toluene, however, is an example of a useful application of this method. 

Alkyl halides can be hydrolyzed to alcohols. Hydroxide ion is usually required, except that especially active substrates such as allylic or benzylic types can be hydrolyzed by water. Ordinary halides can also be hydrolyzed by water, if the solvent is HMPA or A-methyl-2-pyrrolidinone." In contrast to most nucleophilic substitutions at saturated carbons, this reaction can be performed on tertiary substrates without significant interference from elimination side reactions. Tertiary alkyl a-halocarbonyl compounds can be converted to the corresponding alcohol with silver oxide in aqueous acetonitrile." The reaction is not frequently used for synthetic purposes, because alkyl halides are usually obtained from alcohols. 

Benzylic and allylic positions are hydroxylated by CPO in halide-dependent catalytic transformations. Toluene and p-xylene are oxidized to the respective aldehydes and carboxylic acids [247, 248]. Ethylbenzene and other substrates with longer alkyl chains form the respective benzylic/allylic alcohols with high enantio-selectivity. Straight-chain aliphatic and cyclic (Z)-alkenes are hydroxylated, favoring small unsubstituted substrates in which the double bond is not more than two carbon atoms from the terminus. Steric control is observed for benzylic hydroxylations. 

Benzyl glycosides may be prepared by the Koeiiigs-Knorr glycoside synthesis from benzyl alcohol plus a glycosyl halide, or from benzyl alcohol and the sugar in the presence of an acid. ... 

The nucleophilicity of O2 - toward primary alkyl halides (Scheme 7-2) results in an Sn2 displacement of halide ion from the carbon center. The normal reactivity order, benzyl>primary>secondary>tertiary, and leaving-group order, I>Br>OTs>Cl, are observed, as are the expected stereoselectivity and inversion at the carbon center. In dimethylformamide the final product is the dialkyl peroxide. The peroxy radical (ROO), which is produced in the primary step and has been detected by spin trapping,25 is an oxidant that is readily reduced by O2 -to form the peroxy anion (ROO ). Because the latter can oxygenate Me2SO to its sulphone, the main product in this solvent is the alcohol (ROH) rather than the dialkyl peroxide. 

Meerwein-Ponndorf-Verley type asymmetric reduction has also been accomplished with alkyloxy magnesium halides prepared from optically active alcohols. Optically active 2-octyloxy-2-d magnesium bromide reduced butyraldehyde to optically active n-butyl-1-d alcohol (Streitwieser, 1953). Reduction of benzaldehyde with 1-deuteroisobornyloxy magnesium halide produced optically active benzyl-l-d alcohol (Streitwieser and Wolfe, 1957 Streitwieser et al, 1959). 

The alternative synthetic route using the sodium salt of benzyl alcohol and an isopropyl halide would be much less effective because of increased competition from elimination as the alkyl halide becomes more sterically hindered... 

C ( propyl) N phenylmtrone to N phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami noacetone hydiochlonde, 46,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47, 1 /3-chloro a,0 unsaturated, from ke tones and dimethylformamide-phosphorus oxy chloride, 46, 20 from alky 1 halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodumide, and pyndimum tnfluoroacetate, 47, 27 Alkylation, of 2 carbomethoxycyclo pentanone with benzyl chloride 45,7... 

A very similar reagent is benzyl t-butyl imidodicarboxy late 27, which is prepared from benzyl alcohol and benzoyl isocyanate, followed by exhaustive acylation with t-butoxycarbonyl chloride. Aminolysis of the resulting triacylamine yields 27. Treatment of the sodium salt of compound 27 with alkyl halides, followed by hydrolysis, gives primary amines53. 

Mechanistic aspects of the reduction of benzyl halides at mercury have been extensively investigated [35, 38]. From the reduction of benzyl iodide at platinum, Koch and coworkers [39] obtained toluene, bibenzyl, and hydrocinnamonitrile. Electrolysis of benzyl chloride in the presence of acyl chlorides can be used to synthesize alkyl benzyl ketones [40], whereas alcohols are formed by electrolysis of... 

Because of the special structural requirements of the resin-bound substrate, this type of cleavage reaction lacks general applicability. Some of the few examples that have been reported are listed in Table 3.19. Lactones have also been obtained by acid-catalyzed lactonization of resin-bound 4-hydroxy or 3-oxiranyl carboxylic acids [399]. Treatment of polystyrene-bound cyclic acetals with Jones reagent also leads to the release of lactones into solution (Entry 5, Table 3.19). Resin-bound benzylic aryl or alkyl carbonates have been converted into esters by treatment with acyl halides and Lewis acids (Entry 6, Table 3.19). Similarly, alcohols bound to insoluble supports as benzyl ethers can be cleaved from the support and simultaneously converted into esters by treatment with acyl halides [400]. Esters have also been prepared by treatment of carboxylic acids with an excess of polystyrene-bound triazenes here, diazo-nium salts are released into solution, which serve to O-alkylate the acid (Entry 7, Table 3.19). This strategy can also be used to prepare sulfonates [401]. 

Reduction of halides.1 The reagent prepared from NaBH3CN and SnCl2 in a 2 1 ratio does not reduce primary or secondary alkyl halides or aryl halides in ether at 25°, but does reduce tertiary, allyl, and benzyl halides. It is thus comparable to NaBH3CN-ZnCl2 (12, 446). Aldehydes, ketones, and acid chlorides are reduced to alcohols, but esters and amides are inert. 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

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