Alkyl halides formation

Alkyl halide formation from an alcohol and a hydrogen halide affords an important example of a reaction wherein the C-O bond of the alcohol is broken ... 

The reaction is closely related to alkyl halide formation under strongly acidic conditions, whereby conversion of the alcohol to an oxonium salt is a first step ... 

This effect of solvent polarity on the product distribution is in agreement with the proposed reaction scheme. A solvent such as acetone favors a reaction involving charge destruction, such as the alkyl halide formation from the aziridinium ion with the counter ion. Thus acetone favors piperazine formation. A solvent of high polarity favors charge stabilization or charge transfer such as the polymerization steps. Therefore, polymer or piperazine derivatives can be prepared by the proper choice of solvent. 

The transition state for carbocation formation begins to resemble the carbocation. If we assume that structural features that stabilize carbocations also stabilize transition states that have carbocation character, it follows that alkyloxonium ions derived from tertiary alcohols have a lower energy of activation for dissociation and are converted to then-corresponding carbocations faster than those derived from secondary and primary alcohols. Figure 4.14 depicts the effect of alkyloxonium ion structure on the activation energy for, and thus the rate of, carbocation formation. Once the carbocation is formed, it is rapidly captured by halide ion, so that the rate of alkyl halide formation is governed by the rate of carbocation formation. 

The preparation of acetophenone (p. 255) is a modification of this method, the alkyl halide being replaced by an acid chloride, with the consequent formation of a ketone. 

Formation of 2 naphthyl ethers. Alkyl halides and aryl-alkyl halides (e.g. benzyl chloride) are converted into 2-naphthyl ethers thus ... 

Strictly speaking the alkyl halides are esters of the halogen acids, but since they enter into many reactions (t.g., formation of Grignard reagents, reaction with potassium cyanide to yield nitriles, etc.) which cannot be brought about by the other eaters, the alkyl halides are usually distinguished from the esters of the other inorganic acids. The preparation of a number of these is described below. 

Higher alcohols (> C3) react comparatively slowly with sodium because of the slight solubility of the sodium alkoxide in the alcohol a large excess (say, 8 mols) is therefore employed. The mixed ether is distilled off, and the process (formation of alkoxide and its reaction with the alkyl halide) may be repeated several times. The excess of alcohol can be recovered. cj/cloAliphatic alcohols form sodio compounds with difficulty if small pieces... 

The rate at which alcohols are converted to alkyl halides depends on the rate of carbocation formation tertiary alcohols are most reactive primary alcohols and methanol are least reactive... 

In addition to being regioselective dehydrohalogenation of alkyl halides is stereo selective and favors formation of the more stable stereoisomer Usually as m the case of 5 bromononane the trans (or E) alkene is formed m greater amounts than its cis (or Z) stereoisomer... 

We now have a new problem Where does the necessary alkene come from Alkenes are prepared from alcohols by acid catalyzed dehydration (Section 5 9) or from alkyl halides by dehydrohalogenation (Section 5 14) Because our designated starting material is tert butyl alcohol we can combine its dehydration with bromohydrm formation to give the correct sequence of steps... 

When It IS necessary to prepare secondary alkyl halides with assurance that no trace of rearrangement accompanies their formation the corresponding alcohol is first converted to its p toluenesulfonate ester and this ester is then allowed to react with sodium chloride bromide or iodide as described m Section 8 14... 

Dienes with isolated double bonds can be formed when the structure of the alkyl halide doesn t permit the formation of a conjugated diene... 

Alkyl halides by themselves are insufficiently electrophilic to react with benzene Aluminum chloride serves as a Lewis acid catalyst to enhance the electrophihcity of the alkylating agent With tertiary and secondary alkyl halides the addition of aluminum chlonde leads to the formation of carbocations which then attack the aromatic ring... 

Lithium dialkylcuprates react with alkyl halides to produce alkanes by carbon-carbon bond formation between the alkyl group of the alkyl halide and the alkyl group of the dialkylcuprate... 

The most frequently used organocuprates are those m which the alkyl group is pri mary Steric hindrance makes secondary and tertiary dialkylcuprates less reactive and they tend to decompose before they react with the alkyl halide The reaction of cuprate reagents with alkyl halides follows the usual 8 2 order CH3 > primary > secondary > tertiary and I > Br > Cl > F p Toluenesulfonates are somewhat more reactive than halides Because the alkyl halide and dialkylcuprate reagent should both be primary m order to produce satisfactory yields of coupled products the reaction is limited to the formation of RCH2—CH2R and RCH2—CH3 bonds m alkanes... 

A method that achieves the same end result as that desired by alkylation of ammonia but which avoids the formation of secondary and tertiary amines as byproducts is the Gabriel synthesis Alkyl halides are converted to primary alkylamines without contam mation by secondary or tertiary amines The key reagent is the potassium salt of phthal imide prepared by the reaction... 

Among compounds other than simple alkyl halides a halo ketones and a halo esters have been employed as substrates m the Gabriel synthesis Alkyl p toluenesul fonate esters have also been used Because phthalimide can undergo only a single alkyl ation the formation of secondary and tertiary amines does not occur and the Gabriel synthesis is a valuable procedure for the laboratory preparation of primary amines... 

Mazur " obtained 2a-alkyl-5a-H (3) or 4 -alkyl-5 -H products (6) by direct alkylation of either 5a-H (1) or 5 -H-3-keto steroids (4) with alkyl halides under basic conditions. In general, formation and alkylation of the more stable enolate ion is observed in this procedure. 

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