Alkyl hahde from alcohols

Grignard reagents react with ethylene oxide to yield primary alcohols containing two more carbon atoms than the alkyl hahde from which the organometallic componnd was prepared. 

Examples are given of common operations such as absorption of ammonia to make fertihzers and of carbon dioxide to make soda ash. Also of recoveiy of phosphine from offgases of phosphorous plants recoveiy of HE oxidation, halogenation, and hydrogenation of various organics hydration of olefins to alcohols oxo reaction for higher aldehydes and alcohols ozonolysis of oleic acid absorption of carbon monoxide to make sodium formate alkylation of acetic acid with isobutylene to make teti-h ty acetate, absorption of olefins to make various products HCl and HBr plus higher alcohols to make alkyl hahdes and so on. 

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 alkyloxoninm ions derived from tertiary alcohols have a lower energy of activation for dissociation and are converted to their corresponding carbocations faster than those derived from secondary and primary alcohols. Figure 4.14 depicts the effect of alkyloxonium ion stmctnre 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 hahde formation is governed by the rate of carbocation formation. 

A more efficient and more generahy applicable cobalt-catalysed Mizoroki-Heck-type reaction with aliphatic halides was elegantly developed by Oshima and coworkers. A catalytic system comprising C0CI2 (62), l,6-bis(diphenylphosphino)hexane (dpph 73)) and Mc3 SiCH2MgCl (74) allowed for intermolecular subshtution reactions of alkenes with primary, secondary and tertiary alkyl hahdes (Scheme 10.25) [51, 53]. The protocol was subsequently applied to a cobalt-catalysed synthesis of homocinnamyl alcohols starting from epoxides and styrene (2) [54]. 

Scheme 8.27. A representation of the Lncas test showing that in a mixtnre of aqneous HCI and ZnCl2 tertiary alcohols react qnickly to provide tertiary alkyl chlorides, secondary alcohols react more slowly and primary alcohols not at all. The alkyl hahde separates from the aqneous solution as a distinct phase.

The physical properties of alcohols are quite different from the physical properties of alkanes or alkyl hahdes. For example, compare the boiUng points for ethane, chloroethane, and ethanol. 

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl hahdes, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom undergoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

The El dehydration of 2° and 3° alcohols with acid gives clean elimination products without by-products formed from an SnI reaction. This makes the El dehydration of alcohols much more synthetically useful than the El dehydrohalogenation of alkyl hahdes (Section 8.7). Clean elimination takes place because the reaction mixture contains no good nucleophile to react with the intermediate carbocation, so no competing SnI reaction occurs. 

Primary and secondary alcohols, which react only slowly with HBr and HCl, react readily with thionyl chloride and phosphorus trihalides, such as phosphorus tribromide, to give the corresponding alkyl hahdes. The products of these reactions are easily separated ftom the inorganic by-products. Thionyl chloride produces hydrogen chloride and sulfur dioxide, which are released from the reaction as gases. The chloroaUtane remains in solution. 

In Chapter 9, we saw that we can prepare alkenes by dehydrohalogenation. The dehydration of alcohols also gives alkenes, but this reaction occurs with rearrangement of the carbocation, and gives mixtures of products having different carbon skeletons. The elimination of a hydrogen hahde from an alkyl halide is a complex process. We must consider both rcgiochemistry and stereoelectronic effects. These effects are related to the mechanism of the reaction, which may be either E2 or El. 

What are the hmitations of this nvo-step procedure to produce alcohols from alkyl halides First, we need an appropriate alkyl halide. Second, the displacement of halide ion by acetate occurs by an Sj 2 process, which is efficient for primary alkyl hahdes, but occurs at a slower rate for secondary alkyl halides. The process fails for tertiary alkyl halides, which are too sterically hindered to react. 

In light of these significant challenges, Evans and Leahy reexamined the rhodium-catalyzed allylic alkylation using copper(I) enolates, which should be softer and less basic nucleophiles [23]. The copper(I) enolates were expected to circumvent the problems typically associated with enolate nucleophiles in metal-allyl chemistry, namely ehmina-tion of the metal-aUyl intermediate and polyalkylation as well as poor regio- and stereocontrol. Hence, the transmetallation of the lithium enolate derived from acetophenone with a copper(I) hahde salt affords the requisite copper] I) enolate, which permits the efficient regio- and enantiospecific rhodium-catalyzed allylic alkylation reaction of a variety of unsymmetrical acychc alcohol derivatives (Tab. 10.3). 

The reactivities of alkyl halides are in the sequence RI > RBr > RCl and MeX > EtX > PrX. Benzyl hahde reactions with tin do not require catalysts (equation 2). For less reactive halides, the catalysts and promoters employed include metals (sodium, magnesium, zinc, or copper), Lewis bases (amines, triorganophosphines and -stibines, alcohols, or ethers), iodides, and onium salts (R4MX). The use of tin-sodimn alloys can result in tri- or tetraorganotin products. Electrochemical synthesis has also been reported, e.g. the formation of R2SnX2 from the oxidation of anodic tin by RX in benzene solution and the formation of ILtSn from RI (R = Me or NCCH2CH2) and cathodic tin. 

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