Alkyl hahde reaction with alcohols

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. 

The esters of sahcyhc acid account for an increasing fraction of the sahcyhc acid produced, about 15% in the 1990s. Typically, the esters are commercially produced by esterification of sahcyhc acid with the appropriate alcohol using a strong mineral acid such as sulfuric as a catalyst. To complete the esterification, the excess alcohol and water are distilled away and recovered. The cmde product is further purified, generally by distillation. For the manufacture of higher esters of sahcyhc acid, transestetification of methyl sahcylate with the appropriate alcohol is the usual route of choice. However, another reaction method uses sodium sahcylate and the corresponding alkyl hahde to form the desired ester. 

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 oxidation of phenylhydrazine and 1,2-disubstituted hydrazines to hydrazones and diazenes by CI2C proceeds via formation of imstable azomethine imines. The conversion of alcohols into alkyl hahdes is achieved by reaction with CCI4 (or CBr4) in DMF under electrochemical reduction. The reaction of dihalocarbene X2C with DMF to form a VUsmaier reagent (93) is proposed as the key process. The reaction of simple isocyanates (RNCO) with dimethoxycarbene normally gives hydantoin-type products. In the reaction with vinyhsocyanates such as (94), however, hydroindoles (95) are formed in good yields. ... 

The photochemical reaction of ArgSb with styrenes in the presence of Oy results in the formation of 1,2-diarylethanols via peroxyantimony(V) intermediates (Scheme 14.54) [122]. The irradiation of a mixture of Ph2SbSbPh2 and iodoalkaries in air produces alcohols via alkyl diphenylstibonates [123]. Alkyl aryl sulfones are obtained by the BugSb-promoted reaction of tosyl chloride with alkyl hahdes [124]. 

Clearly, the steric crowding that influences reaction rates in Sn2 processes plays no role in SnI reactions. The order of alkyl hahde reactivity in SnI reactions is the same as the order of carbocation stability the more stable the carbocation, the more reactive the alkyl halide. We have seen this situation before in the reaction of alcohols with hydrogen halides (Section 4.12), in the acid-catalyzed dehydration of alcohols (Section 5.9), and in the conversion of alkyl hahdes to alkenes by the El mechanism (Section 5.17). As in these other reactions, an electronic effect, specifically, the stabilization of the carbocation intermediate by alkyl substiments, is the decisive factor. 

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]. 

If the solvent is water or if it contains water, the bimolecular (collision) processes between a neutral substrate and a charged nucleophile (such as nucleophilic acyl addition reactions and nucleophilic displacement with alkyl hahdes) are slower due to solvation effects. On the other hand, water is an excellent solvent for the solvation and separation of ions, so unimolecular processes (which involve ionization to carbocations see Chapter 11, Section 11.6) may be competitive. If the solvent is protic (ethanol, acetic acid, methanol), ionization is possible, but much slower than in water. However, ionization can occiu- if the reaction is given sufficient time to react. In other words, ionization is slow, but not impossible. An example of this statement is the solvolysis of alcohols presented in Chapter 6 (Section 6.4.2). Based on this observation, assume that ionization (unimolecular reactions) will be competitive in water, but not in other solvents, leading to the assumption that bimolecular reactions should be dominant in solvents other than water. This statement is clearly an assumption, and it is not entirely correct because ionization can occur in ethanol, acetic acid, and so on however, the assumption is remarkably accurate in many simple reactions and it allows one to begin making predictions about nucleophilic reactions. 

When simple primary alkyl halides are permitted to react with alkoxide anions, substitution of the alkoxide for the halide occurs or, alternatively, the alkyl group has been substituted for the hydrogen which was on oxygen. Variants of this reaction, the Williamson ether synthesis, have been seen before as a substitution reaction at carbon (of the alkyl hahde) and will be seen again as an addition reaction of alcohols. 

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. 

The most generally useful method of preparing ethers is by the Williamson ether synthesis, in which an alkoxide ion reacts with a primary alkyl hahde or tosylate in an Sn2 reaction. As we saw earlier in Section 13.2, the alkoxide ion is normally prepared hy reaction of an alcohol with a strong base such as sodium hydride, NaH. 

Another way a primary or secondary alcohol can be activated for a subsequent reaction with a nucleophile—instead of converting it into an alkyl hahde—is to convert it into a sulfonate ester. A sulfonate ester is formed when an alcohol reacts with a sulfonyl... 

Solution Conversion of the alcohol to the ether hy way of an alkyl halide requires two successive 8 2 reactions (1) attack of Br on the hromophosphite and (2) attack of CH3O on the alkyl hahde. Each 8 2 reaction takes place with inversion of configuration, so the final product has the same configuration as the starting material. 

The reduction of alkyl hahdes has been important in many syntheses. Sodium cyanoborohydride in HMPA will reduce alkyl iodides, bromides, and tosylates selectively in the presence of ester, amide, nitro, chloro, cyano, alkene, epoxide, and aldehyde groups [118]. Tri-n-butyltin hydride will replace chloro, bromo, or iodo groups with hydrogen via a free radical chain reaction initiated by thermal decomposition of AIBN [119]. Other functionality such as ketones, esters, amides, ethers, and alcohols survive unchanged. The less toxic tris(trimethylsilyl) silane can be used similarly [120]. 

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. 

Elimination reactions of primary alcohols occurs by an E2 mechanism in an acid-cataly2ed reaction. First, the acid protonates the oxygen of a primary alcohol to give a primary alkyl oxonium ion. Then, water is lost by an E2 mechanism because a primary carbocation is too unstable to form in an El process. This concerted step resembles the reaction of primary alkyl hahdes with a base. The proton of the alkyl oxonium ion is deprotonated by a Lewis base, which is water in the dehydration of alcohols. The electron pair in the C—H bond moves to form a carbon-carbon double bond, and the electron pair of the C—O bond is retained by the oxygen atom. The reaction with ethanol illustrates the process. In both the El process and the E2 dehydration reaction, the acid serves only as a catalyst. It is regenerated in the last step of the reaction. 

Alkynide ions react with carbonyl groups in much the same way as Grignard reagents do. We recall that these ions are effective nucleophiles that will displace a hahde ion ftom an alkyl halide to give an alkylated alkyne. The alkynides are prepared in an acid-base reaction with acetylene or a terminal alkyne using sodium amide in ammonia. If a carbonyl compound is then added to the reagent, an alcohol forms after acid work-up. If the alkynide is derived ftom acetylene, an acetylenic alcohol forms. 

A mechanistically related reaction occurs when epoxides react with Grignard reagents to produce alcohols. The carbon skeleton contains two more carbon atoms than the starting alkyl hahde. The sequence of reactions is shown below. 

Heating the adduct of ethylene oxide and sulfur dioxide with primary alcohols in the presence of alkaH hydhdes or a transition-metal haHde yields dialkyl sulfites (107). Another method for the preparation of methyl alkyl sulfites consists of the reaction of diazomethane with alcohoHc solutions of sulfur dioxide (108). 

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). 

When we convert an alcohol to an alkyl halide, we carry out the reaction in the presence of acid and in the presence of halide ions, and not at elevated temperature. Hahde ions are good nucleophiles (they are much stronger nucleophiles than water), and since halide ions are present in high concentration, most of the carbocations react with an electron pair of a halide ion to form a more stable species, the alkyl halide product. The overall result is an S l reaction. 

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