Elimination from alkyl halides

Q Show how alkenes can be synthesized by eliminations from alkyl halides and alcohols. 

At the center of the spectrum is the transition state wc have described before for elimination from alkyl halides both C- H and C X bonds are broken to a considerable extent, the transition state has considerable alkene character, and orientation is SaytzefT. 

In eliminations from alkyl halides, an increase in the proportion of the 1-alkene (Hofmann product) is often accompanied by a decrease in the ( )/(Z) 2-aIkene ratio as the base/solvent system is changed from EtOK/EtOH to Bu OK/Bu OH (see Table 7). ... 

One of the most commoidy used methods for forming carbon-carbon double bonds is by -elimination reactions of the types shown in Scheme 2.1, where X = e.g. OH, OCOR, halogen, OSO2R, NRa, etc. Included among these reactions are acid-catalysed dehydrations of alcohols, solvolytic and base-induced eliminations from alkyl halides or sulfonates and the Hofmann elimination from quaternary ammonium salts. They proceed by both E2 (elimination bimolecular) and E1 (elimination... 

The potassium complex of mono-aza-18-crown-6 (80) is a self-solvating base potentially useful for performing clean E2 eliminations from alkyl halides in non-polar solvents,whilst avoiding the loss of reactivity and changes in product distribution sometimes observed in such media due to base-cation association. 

One of the likeliest explanations for the formation of the less stable carbon-carbon double bond is that Hofmann elimination is governed largely by steric factors, namely the bulk of the — NR3+ group. The hydroxide ion preferentially approaches and removes the least hindered a-hydrogen and gives the least substituted alkene as product. Eor the same reason, bulky bases such as (CH3)3CO"K+ also give Hofmann elimination from alkyl halides. 

Alkynes can be prepared by the elimination of HX from alkyl halides in much the same manner as alkenes (Section 7.1). Treatment of a 1,2-dihaloaJkane (a vicinal dihalide) with excess strong base such as KOH or NaNH2 results in a twofold elimination of HX and formation of an alkyne. As with the elimination of HX to form an alkene, we ll defer a discussion of the mechanism until Chapter 11. 

In 1,2-eliminations involving carbon atoms (i.e. most), the atom from which Y is lost is usually designated as the l-(a-) carbon and that losing (usually) H as the 2-(/ -) carbon in the older a/J-terminology, the a- is commonly omitted, and the reactions are referred to as p-eliminations. Among the most familiar examples are base-induced elimination of hydrogen halide from alkyl halides—this almost certainly the most common elimination of all—particularly from bromides (1) ... 

Much evidence supports the conclusion that the elimination of the group HX from alkyl halides by bases is a trans elimination reaction. This means that the atoms H and X leave from the opposite site of the incipient double bond. It is mostly explained by assuming that the electrons which are left by the leaving proton and which will form the double bond prefer to attack the leaving group X from the rear (50). The transition state for the elimination, if it is concerted, is most stable if H, X, and the carbon atoms 1 and 2 lie on one plane, which in most molecules is best realized in the trans position (51). ... 

Consideration of the oxidation level reveals diat while one carbon is reduced (the one to which hydrogen adds), die other is oxidized (die one to which the oxygen adds). There is no net change in oxidation level of the alkene functional group. Likewise die reverse processes of these addition reactions, namely, elimination of HX from alkyl halides and dehydration of alcohols to give alkenes, are not redox processes. Additions of water to alkynes is analogous. In this case, however, the product is a ketone, the oxidation level of the ketone is seen to be the same as the alkyne, and so no net change in oxidation level has occurred. 

The target is now cyclopentanol. Alcohols can be prepared from alkyl halides by reaction with hydroxide ion as the nucleophile. Again, however, the combination of a strongly basic nucleophile and a secondary alkyl halide will result in an unacceptable amount of elimination. A better plan is to treat bromocyclopentane with acetate ion in an aprotic solvent such as DM SO. followed by cleavage of the ester to cyclopentanol ... 

DBU or DBN will generally eliminate HX from alkyl halides to give alkenes. In these two examples, the products were intermediates in the synthesis of natural products. 

You saw in Chapter 19 that elimination reactions can be used to make alkenes from alcohols using acid or from alkyl halides using base. The acid-catalysed dehydration of tertiary butanol works well... 

The reductive elimination product from alkyl halide complexes L M(X)yR2 is usually the alkane R—R. In some cases, however, C—X bond formation may compete with C—C elimination, as in (dppe)Pt(I)Me3 101... 

Recall from Chapters 8 and 9 that alkenes can be prepared from alkyl halides and alcohols via elimination reactions. For example, dehydrohalogenation of alkyl halides with strong base yields alkenes via an E2 mechanism (Sections 8.4 and 8.5). 

Sodium sulfhydride (NaSH) is a much better reagent for the formation of thiols (mercaptans) from alkyl halides than H2S and is used much more often. It is easily prepared by bubbling H2S into an alkaline solution, but hydrosulfide on a supported polymer resin has also been used. " The reaction is most useful for primary halides. Secondary substrates give much lower yields, and the reaction fails completely for tertiary halides because elimination predominates. Sulfuric and sulfonic esters can be used instead of halides. Thioethers (RSR) are often side products. The conversion can also be accomplished under neutral conditions by treatment of a primary halide with F and a tin sulfide, such as PhsSnSSnPhs. An indirect method for the preparation of a thiol is the reaction of an alkyl halide with thiourea to give an isothiuronium salt (119), and subsequent treatment with alkali or a... 

Since sodium acetylide is the salt of the extremely weak acid, acetylene, the acetylide ion is an extremely strong base, stronger in fact than hydroxide ion. In our discussion of the synthesis of alkenes from alkyl halides (Sec. 5.13), we saw that the basic hydroxide ion causes elimination by abstracting a hydrogen ion. It is not surprising that the even more basic acetylide ion can also cause elimination. 

Alkenes are prepared from alcohols either by direct dehydration or by de-hydrohalogenation of intermediate alkyl halides to avoid rearrangement we often select dehydrohalogenation of halides even though this route involves an extra step. (Or, sometimes better, we use elimination from alkyl sulfonates.)... 

You saw in Chapter 19 that elimination reactions can be used to make alkenes from alcohols using acid or from alkyl halides using base. The acid-catalysed dehydration of tertiary butanol works well because the double bond has no choice about where to form. But the same reaction on s-butanol is quite unselective—as you would expect, the more substituted alkene is formed (almost solely, as it happens) but even then it s a mixture of geometrical isomers. 

The synthesis of stereodefined acyclic alkenes via 3-elimination reactions—such as (1) dehydration of alcohols, (2) base-induced eliminations of alkyl halides or sulfonates (tosyl or mesyl esters), and (3) Hofmann eliminations of quaternary ammonium salts—often suffers from a lack of regio- and stereoselectivity, producing mixtures of isomeric alkenes. 

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