2- , with alkoxide ions

5-Dicyano-3,6-dimethylpyrazine shaken with sodium ethoxide at room temperature gave 2-cyano-5-ethoxy-3,6-dimethylpyrazine and 2-cyano-5-hydroxy-3,6-dimethylpyrazine (288). Reactions of 2-chloro-6-cyanopyrazine with sodium methoxide have been described in Sections 1 A(2)(c). 

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Chloro-5-arylisoxazoles undergo nucleophilic displacement with alkoxide ion. Halogen atoms in the 5-position of the isoxazole nucleus are readily displaced if an activating group is present in the 4-position (63AHC(2)365). 

This group has also developed two ring-contraction systems of potential use in crown synthesis. In the first of these, extrusion of a phenylphosphine oxide unit results from treatment with alkoxide ion. In the second, similar conditions initiated decarbonyla-tion of a bis-pyridyl ketone Despite the apparent potential of these methods for crown synthesis, direct formation of crowns by processes which involve them do not appear to have enjoyed great success thus far. 

The reaction of chlorodifluorotnethane with alkoxide ions generated in low concentration from halide ions and epoxides [28, 29] is an interesting, higher temperature method that gives good to excellent yields of gem-difluorocyclo-propanes from just moderately nucleophilic olefins (equation 9)... 

The indirect deactivation in 2-amino-4-chloroquinoline (187) requires vigorous conditions (potassium hydroxide in hot ethylene glycol, or boiling propanolic propoxide for 16 hr) to displace the chloro group, which is stable to aqueous alkali and to hydriodic acid. The direct deactivation in 5-amino-2-chloro-3-cyano-6-methyl-pyridine (188) prevents reaction with alkoxide ion under conditions which produce smooth reaction of the des-amino analog. 

The net effect of nucleophilic acyl substitution is the replacement of the leaving group by the entering nucleophile. We ll see in Chapter 21, for instance, that acid chlorides are rapidly converted into esters by treatment with alkoxide ions (Figure 4). 

The reaction of alkyl sulfates with alkoxide ions is quite similar to 10-12 in mechanism and scope. Other inorganic esters can also be used. One of the most common usages of the reaction is the formation of methyl ethers of alcohols and phenols by treatment of alkoxides or aroxides with methyl sulfate. The alcohol or phenol can be methylated directly, by treatment with dimethyl sulfate and alumina in cyclohexane. Carboxylic esters sometimes give ethers when treated with alkoxides (Bal2 mechanism, p. 473) in a very similar process (see also 10-24). 

The reaction of oc-halo ketones (chloro, bromo, or iodo) with alkoxide ions rearranged esters is called the Favorskii rearrangement. 

Now that we have seen how to deprotonate an alcohol (to form an alkoxide), the obvious question is what can we do with alkoxide ions We have already seen that alkoxide ions can be used as strong bases. But alkoxides can also function as strong nucleophiles. For example, consider the following Sn2 reaction ... 

The coordinated macrocycle readily reacts with alkoxide ions to yield products of type (71) (Taylor, Urbach Busch, 1969). In so doing additional flexibility is imparted to the ring which may reduce ring strain and, in part, provide a driving force for the reaction. Thus the coordinated imine carbons appear predisposed to attack by such nucleophiles. Based on this knowledge, elegant template syntheses of three-dimensional derivatives have been performed. The syntheses involved the reaction of [M(taab)]2+ (M = Ni, Cu) with the dialkoxide ions derived from bis(2-hydroxyethyl)sulphide or bis(2-hydroxyethyl)methylamine (Katovic, Taylor Busch, 1969). The products were demonstrated to be monomeric square-pyramidal complexes of type (72). The condensation... 

There has been a useful review of phase-transfer catalysis in nucleophilic aromatic substimtion. A comparison has been reported of the reactions with nucleophiles of l-chloro-2,4-dinitrobenzene (substimtion) and 4-nitrophenyl diphenyl phosphate (dephosphorylation) in neutral micelles of dodecyl (10) and (23) polyoxyethylene glycol. In the substimtion reaction considerable amounts of ether may be formed by reaction with alkoxide ions at the micellar surface. Differences in reactivity of the two substrates are probably due to differences in their location in the micellar structures. ... 

The 0ew-N3P3(NH2)2Cl4 when allowed to react with alkoxide ion in the corresponding alcohol gives rearranged cis and trans alkoxy derivatives, non-gem-N3P3(NH2)2(OR)4 (R = Me, Et, Pr" or Bu") (Eq. 29) [168-170]. However,... 

The reaction of a-haloketones (chloro, bromo or iodo) with alkoxide ions to give rearranged esters is called Favorskii rearrangement. For example, 2-chlorocyclohexanone is converted to the methyl ester of cyclopentane carboxylic acid by treatment with sodium methoxide in ether. 

Several 1,1-disubstituted olefins with electrophilic groups react with alcohols to undergo addition reactions, and with alkoxide ions to undergo substitution reactions to afford ortho esters [120a-c, 125a, b, 130-137] (Eq. 37). 

The exchange of one alkoxy group for another is very rare for ethers, though it has been accomplished with reactive R, for example, diphenylmethyl with p-toluenesulfonic acid as a catalyst,611 and by treatment of alkyl aryl ethers with alkoxide ions ROAr + R O — ROR + ArO. 612 However, acetals and ortho esters undergo transetherification readily,613 for example,614... 

The requisite haJohydrm anion intermediate is normally secured by the treatment of an appropriate ah ioketone or a-halosldehyde with alkoxide ion under suitable conditions. 

This electrophilic assistance could account for the observed solvent and counterion effects. The stereochemistry of substitution of alkoxy, mercapto and fluorosilanes with alkoxide ion depends dramatically on the composition of the solvent4. As the percentage... 

The monosubstitution of vinyl bromide (Truce et al., 1956b) probably occurs via elimination-addition owing to the low reactivity of the halo-olefin. Acetylene is the only product formed with alkoxide ions or aniline. 

That the substitution mechanism depends on the nature of the nucleophile is shown by the formation of the ketene acetals (151) from the reaction of vinylidene chloride with alkoxide ions. It was suggested that two consecutive eliminations-additions take place, and that in both cases the alkoxide attacks the acetylene at the substituted carbon (Kuryla and Leis, 1964). Since chloroacetylene (132) is also an inter-... 

Many examples of double bond migration appear in the reactions of dihalocyclo-propanes with alkoxide ion, in which the halocyclopropene is a presumed intermediate. Thus dehydrohalogenation of 2,3-dialkyl-l,l-dichlorocyclopropanes provides a very simple route to methylenecyclopropanes, which often rearrange on heating,... 

Allylic halides may be readily converted into ethers by reaction with alkoxide ion in refluxing DMF. In the case of a bis-haloallyl compound, a reasonable yield of mono alkoxy-lated product may be formed in some instances (equation 30)246. The product may then be further elaborated by formation of a Grignard reagent at the remaining halogen atom. 

Ethers can be prepared by using an alcohol or its conjugate base, an alkoxide ion. as the nucleophile. A general equation for the reaction with alkoxide ion is... 

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