Alcohols 0-halo

Formation of Alkyl Halides from Alcohols Halo-de-hydroxylation... 

Annulation by Halo Alcohols, Halo Phenols, and Phenols. 158... 

It is frequently advisable in the routine examination of an ester, and before any derivatives are considered, to determine the saponification equivalent of the ester. In order to ensure that complete hydrolysis takes place in a comparatively short time, the quantitative saponi fication is conducted with a standardised alcoholic solution of caustic alkali—preferably potassium hydroxide since the potassium salts of organic acids are usuaUy more soluble than the sodium salts. A knowledge of the b.p. and the saponification equivalent of the unknown ester would provide the basis for a fairly accurate approximation of the size of the ester molecule. It must, however, be borne in mind that certain structures may effect the values of the equivalent thus aliphatic halo genated esters may consume alkali because of hydrolysis of part of the halogen during the determination, nitro esters may be reduced by the alkaline hydrolysis medium, etc. 

Halo- and dihalobismuthines are crystalline soHds, most of which have melting poiats above 100°C. They are, ia general, very reactive compounds and are decomposed by moisture, alcohols, and ammonia (118). Dialkylhalobismuthines are especially sensitive substances. They are spontaneously indammable ia air and may decompose even when water and oxygen are excluded. The diaryl compounds are more stable, but they should also be handled with caution. Some of them are powerhil stemutators (119). 

Many other reactions of ethylene oxide are only of laboratory significance. These iaclude nucleophilic additions of amides, alkaU metal organic compounds, and pyridinyl alcohols (93), and electrophilic reactions with orthoformates, acetals, titanium tetrachloride, sulfenyl chlorides, halo-silanes, and dinitrogen tetroxide (94). 

Oxiranes react with iodotrimethylsilane to give silylated halo alcohols e.g. 60) which can be converted to allylic alcohols (Scheme 53) (80JOC2579, 80TL2329) cf. other syntheses of allylic alcohols (Sections 5.05.3.2.2, 5.05.3.4.3(0 and Hi)). 

A large variety of methods is applicable to the formation of isolated double bonds. This permits selection of reagents compatible with other functionality present. Alcohol dehydration, ester elimination and other nonreductive p eliminations are the most common methods. Reductive elimination of halo-hydrins, vic-dihalides, etc., and of a variety of ketone derivatives has also been used. 

The reductive elimination of halohydrins provides a means of introduction of double bonds in specific locations, particularly as the halohydrin may be obtained from the corresponding a-halo ketone. This route is one way of converting a ketone into an olefin. (The elimination of alcohols obtainable by reduction has been covered above, and other routes will be discussed in sections IX and X.) An advantage of this method is that it is unnecessary to separate the epimeric alcohols obtained on reduction of the a-bromo ketone, since both cis- and tran -bromohydrins give olefins (ref. 185, p. 251, 271 cf. ref. 272). Many examples of this approach have been recorded. (For recent examples, see ref. 176, 227, 228, 242, 273.) The preparation of an-drost-16-ene (123) is illustrative, although there are better routes to this compound. 

Borohydrides reduce a-substituted ketones to the corresponding a-substituted alcohols, and such products can be further reduced to olefins (see section VIII). Other reagents serve, through participation of the carbonyl group, to remove the substituent while leaving the ketone intact. The zinc or chromous ion reduction of a-halo ketones is an example of this second type, which is not normally useful for double bond introduction. However, when the derivative being reduced is an a,jS-epoxy ketone, the primary product is a -hydroxy ketone which readily dehydrates to the a,jS-unsaturated ketone. Since... 

The accelerative effect of quaternization on the reactivity of 1-halo groups toward water, alcohol, or ammonia has been reported. ... 

The rearrangement with ring contraction probably is the most important synthetic application of the Favorskii reaction it is for example used in the synthesis of steroids. Yields can vary from good to moderate. As solvents diethyl ether or alcohols are often used. With acyclic a-halo ketones bearing voluminous substituents in a -position, yields can be low a tcrt-butyl substituent will prevent the rearrangement. 

Yet another example of an electrophilic addition is the reaction of alkenes with the hypohalous acids HO—Cl or HO-Br to yield 1,2-halo alcohols, called halohydrins. Halohydrin formation doesn t take place by direct reaction of an alkene with HOBr or HOC1, however. Rather, the addition is done indirectly by reaction of the alkene with either Br2 or Cl2 in the presence of water. 

To now solve the problem posed at the beginning of this section, it s possible to use a halo alcohol in a Grignard reaction by employing a protection sequence. For example, we can add 3-bromo-l-propanol to acetaldehyde by the route shown in Figure 17.9. 

Halo-l-benzothiepins 4 can be synthesized by the treatment of 7a-halobenzo[fe]cyclopropa-[e]thiopyran-7-ols 2 with hydrogen bromide and subsequent hydrogen bromide elimination from the 2,4-dihalo-2,3-dihydro-l-benzothiepins 3 by l,5-diazabicyclo[4.3.0]non-5-ene (DBN).9 The alcohols 2 are prepared by Grignard reaction of the corresponding 7a-halobenzo[ft]cyclopropa[c]thiopyran-7-ones l18 and are used for the synthesis without purification. The intermediate dihalodihydro-l-benzothiepins 3 are not isolated due to their thermal lability related and more stable compounds are described in Section 2.1.2.1. 

Corey used a chiral bromoborane 75 (1.1 equiv.) to promote the addition of tert-butyl bromoacetate (76) to aromatic, aliphatic, and a,P-unsaturated aldehydes to give the halo alcohols 77 with high enantio- and diastereoselectivities (Table 1.10) [35]. 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

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 imidazole nucleus is often found in biologically active molecules,3 and a large variety of methods have been employed for their synthesis.4 We recently needed to develop a more viable process for the preparation of kilogram quantities of 2,4-disubstituted imidazoles. The condensation of amidines, which are readily accessible from nitriles,5 with a-halo ketones has become a widely used method for the synthesis of 2,4-disubstituted imidazoles. A literature survey indicated that chloroform was the most commonly used solvent for this reaction.6 In addition to the use of a toxic solvent, yields of the reaction varied from poor to moderate, and column chromatography was often required for product isolation. Use of other solvents such as alcohols,7 DMF,8 and acetonitrile9 have also been utilized in this reaction, but yields are also frequently been reported as poor. 

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. °... 

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