Halo-ethers

Rearrangement of a,/B-epoxy ketones to ftdicarbonyl isomers, 307 Reductive alkylation, 97 Reductive cleavage of halo ethers, 264 Reductive degradation of 19-substitutional steroids, 277, 278 Reformatsky reaction, 139 Removal of the C-10 substituent in steroids. 272... 

In general the Stork reaction gives moderate yields with simple alkyl halides better yields of alkylated product are obtained with more electrophilic reactants such like allylic, benzylic or propargylic halides or an a-halo ether, a-halo ester or a-halo ketone. An example is the reaction of 1-pyrrolidino-l-cyclohexene 6 with allyl bromide, followed by aqueous acidic workup, to yield 2-allylcyclohexanone ... 

This procedure illustrates a general method for the stereoselective synthesis of ( P)-disubstitnted alkenyl alcohols. The reductive elimination of cyclic /3-halo-ethers with metals was first introduced by Paul3 and one example, the conversion of tetrahydrofurfuryl chloride [2-(chloromethyl)tetrahydrofuran] to 4-penten-l-ol, is described in an earlier volume of this series.4 In 1947 Paul and Riobe5 prepared 4-nonen-l-ol by this method, and the general method has subsequently been applied to obtain alkenyl alcohols with other substitution patterns.2,6-8 (I )-4-Hexen-l-ol has been prepared by this method9 and in lower yield by an analogous reaction with 3-bromo-2-methyltetra-hydropyran.10... 

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

Halo-ethers can be formed by the reaction of alkenyl alcohols with various reagents. Hept-6-en-l-ol reacts with (collidine)2l PFg, for example, to form 2-iodomethyl-1 -oxacycloheptane. ... 

In a related process, a-halo ethers can be prepared by treatment of aldehydes and ketones with an alcohol and HX. The reaction is applicable to aliphatic aldehydes and ketones and to primary and secondary alcohols. The addition of HX to an aldehyde or ketone gives tx-halo alcohols, which are usually unstable, though exceptions are known, especially with perfluoro and perchloro species. °... 

The elimination of OR and halogen from P-halo ethers is called the Boord reaction. It can be carried out with zinc, magnesium, sodium, or certain other reagents.The... 

See Ref. 150, p. 136, for reagents that produce alkenes from p-halo ethers and esters, and from halohydrins. 

Alkylation of enamines requires relatively reactive alkylating agents for good results. Methyl iodide, allyl and benzyl halides, a-halo esters, a-halo ethers, and a-halo ketones are the most successful alkylating agents. The use of enamines for selective alkylation has largely been supplanted by the methods for kinetic enolate formation described in Section 1.2. 

There are very few precedents for the reaction of cyclic a-halo ethers with carbanions. Zelinski and coworkers114 and Schudel and Rice115 reported the preparation of diethyl DL-tetrahydropyran-2-ylmalonate (137) by treatment of 2-bromo- or 2-chloro-tetrahydropyran (136) with diethyl sodiomalonate. The product was subsequently converted into the malonic and acetic acid derivatives, 138 and 139, respectively. The same sequence has also been reported by other workers.116... 

Determination of Certain Halo Ethers in Municipal and Industrial Discharges using LLE and GC... 

Drew, R.T., Laskin, S., Kuschner, M., and Nelson, N. Inhalation carcinogenicity of alpha halo ethers. I. The acute inhalation toxicity of chloromethyl methyl ether and bis(chloromethyl)ether, Arch. Environ. Health, 30(2) 61-69, 1975. 

Reaction of Metallated Acetylenes with Alkyl Halides, a-Halo-ethers, Epoxides and Alkyl Orthoformates... 

Iron-acyl enolates, such as 2, prepared by x-deprotonation of the corresponding acyl complexes with lithium amides or alkyllithiums, are nearly always generated as fs-enolates which suffer stereoselective alkylation while existing as the crmt-conformer which places the carbon monoxide oxygen anti to the enolate oxygen (see Section 1.1.1.3.4.1.). These enolates react readily with strong electrophiles, such as primary iodoalkanes, primary alkyl sulfonates, 3-bromopropenes, (bromomethyl)benzenes and 3-bromopropynes, a-halo ethers and a-halo carbonyl compounds (Houben-Weyl, Volume 13/9 a, p 413) (see Table 6 for examples). 

Reaction between alkoxides and gwt-dihalides (Williamson) or ot-halo ethers... 

Cl—H, ROH I Cl—C—OR I acidic catalysts Section 16-4D, synthesis of a-halo ethers... 

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