Alkylation, mechanism with alcohols

The resulting mechanism is therefore the usual one allowing, e.g., the Williamson ether synthesis through alkylation of alkyl halides with alcohols in the presence of 50% NaOH and Bu4N HS04 as catalyst [27]. 

Alcohols. Toussaint and Hennion alkylated benzene with alcohols, using boron trifluoride as the acid catalyst and ph( phorus pentoxide, sulfuric acid, and benzenesulfonic acid as assistants. They explained the mechanism on the basis of a dehydration of the alcohol to an olefin ... 

While developing the connections between structure reaction and mechanism we will also extend the fundamentals of lUPAC nomenclature to functional group families beginning with alcohols and alkyl halides... 

The mechanism of the alkylation reaction is similar to curing. The methylo1 group becomes protonated and dissociates to form a carbonium ion intermediate which may react with alcohol to produce an alkoxymethyl group or with water to revert to the starting material. The amount of water in the reaction mixture should be kept to a minimum since the relative amounts of alcohol and water determine the final equiHbrium. 

A considerable amount of hydrobromic acid is consumed in the manufacture of inorganic bromides, as well as in the synthesis of alkyl bromides from alcohols. The acid can also be used to hydrobrominate olefins (qv). The addition can take place by an ionic mechanism, usually in a polar solvent, according to Markownikoff s rule to yield a secondary alkyl bromide. Under the influence of a free-radical catalyst, in aprotic, nonpolar solvents, dry hydrogen bromide reacts with an a-olefin to produce a primary alkyl bromide as the predominant product. Primary alkyl bromides are useful in synthesizing other compounds and are 40—60 times as reactive as the corresponding chlorides (6). 

Evidence for this mechanism is as follows The addition of pyridine to the mixture of alcohol and thionyl chloride results in the formation of alkyl halide with inverted configuration. Inversion results because the pyridine reacts with ROSOCl to give ROSONC5H5 before anything further can take place. The Cl freed in this process now attacks from the rear. The reaction between alcohols and thionyl chloride is second order, which is predicted by this mechanism, but the decomposition by simple heating of ROSOCl is first order. ... 

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). 

A mechanism proposed 87) for the alkaline hydrolysis of tetraethyl pyrophosphate, which is markedly accelerated by HPO e ions, has been substantiated by isotopic labeling 88). The nucleophilic attack by HPOJp on the symmetrical pyrophosphate 131 is considered to lead initially to the unsymmetrical P P1-diethyl pyrophosphate dianion 132 which decomposes spontaneously under the conditions of reaction to give the diethyl phosphate anion and POf 102. The latter reacts with water to form inorganic phosphate and with alcohols suclj as methanol and ethylene glycol to produce alkyl phosphates. 

Figure 8.17 Reaction of an alkyl halide with hydroxide ion. (a) A primary halide reacts by an SN2 mechanism, causing Walden inversion about the central, chiral carbon, (b) A tertiary halide reacts by an SN1 mechanism (the rate-determining step of which is unimolecular dissociation, minimizing the extent of Walden inversion and maximizing the extent of racemization). Secondary alcohols often react with both Sn 1 and SN2 mechanistic pathways proceeding concurrently...

In the alkoxycarbonylation, the hydride mechanism initiates through the olefin insertion into a Pd - H bond, followed by the insertion of CO into the resulting Pd-alkyl bond with formation of an acyl intermediate, which undergoes nucleophilic attack of the alkanol to give the ester and the Pd - H+ species, which initiates the next catalytic cycle [35,40,57,118]. Alternatively, it has been proposed that a ketene intermediate forms from the acyl complex via /3-hydride elimination, followed by rapid addition of the alcohol [119]. In principle the alkyl intermediate may form also by protonation of the olefin coordinated to a Pd(0) complex [120,121]. 

The need for great care to avoid the possibility of detonation of perchloryl compounds by exposure to shock, overheating or sparks is stressed. The compounds are generally more sensitive to impact than mercury fulminate and are of comparable sensitivity to lead azide [1], A range of highly explosive alkyl perchlorates [2] and perchlorylamines [3] have been prepared by interaction of dichlorine heptaoxide with alcohols or amines in carbon tetrachloride solution. The solutions of the products were not sensitive to mechanical shock and could... 

In what appears, initially, to be a closely similar reaction, acid chlorides react with alkyl halides under solidtliquid two-phase conditions using sodium hydrogen carbonate in the presence of sodium iodide and tetra-n-butylammonium bromide [45]. Although the mechanism is not clear, it has been proposed that the acid chloride is initially converted into the carboxylate anion. It is also probable that the halogen interchange between the sodium iodide and the alkyl halides enhances their reactivity. Although the yields are high, the availability of the alkyl halides and alcohols are usually similar and there appears to be little to commend this process over the catalysed reaction of the acid chlorides with the alcohols. 

A possible mechanism for the P-alkylation of secondary alcohols with primary alcohols catalyzed by a 1/base system is illustrated in Scheme 5.28. The first step of the reaction involves oxidation of the primary and secondary alcohols to aldehydes and ketones, accompanied by the transitory generation of a hydrido iridium species. A base-mediated cross-aldol condensation then occurs to give an a,P-unsaturated ketone. Finally, successive transfer hydrogenation of the C=C and C=0 double bonds of the a,P-unsaturated ketone by the hydrido iridium species occurs to give the product. 

Iodide is a good nucleophile. It attacks the least substituted carbon of the oxonlum ion formed in step 1 and displaces an alcohol molecule by S 2 mechanism. Thus, in the cleavage of mixed ethers with two different alkyl groups, the alcohol and alkyl Iodide formed, depend on the nature of alkyl groups. When primary or secondary alkyl groups are present. It Is the lower alkyl group that forms kyl Iodide (Sn2 reaction). 

The mechanism of the photochemical alkylation shows particular characteristics as regards the formation of alkyl radicals, the reaction of these radicals with the heteroaromatic substrates, and the rearomatization of the intermediate products. A variety of alkylating agents (hydrocarbons, alcohols, amines, carboxylic acids, amino acids) have been used for photochemical and y-ray-induced alkylation. " ... 

The reaction of halogenotriphenylphosphonium halides (triphenyl-phosphine dihalides) with alcohols is a useful method for the synthesis of alkyl halides (see Section II,2b p. 239). It has been found88 that (alkoxymethylene)dimethyliminium halides are formed in the reactions of these reagents with alcohols in N,N-dimethylformamide a possible mechanism is shown. Hydrolysis of the (alkoxymethylene)-dimethyliminium halide intermediate affords a formic ester, whereas... 

Evidence for this mechanism is as follows the addition of pyridine to the mixture of alcohol and thionyl chloride results in the formation of alkyl halide with inverted configu-... 

Alkyl halides are often used as substrates instead of alcohols. In such cases the salt of the inorganic acid is usually used and the mechanism is nucleophilic substitution at the carbon atom. An important example is the treatment of alkyl halides with silver nitrate to form alkyl nitrates. This is used as a test for alkyl halides. In some cases there is competition from the central atom. Thus nitrite ion is an ambident nucleophile that can give nitrites or nitro compounds (see 0-60).731 Dialkyl or aryl alkyl ethers can be cleaved with anhydrous sulfonic acids.732... 

Thioethers (sulfides) can be prepared by treatment of alkyl halides with salts of thiols (thiolate ions).7S2 R may be alkyl or aryl. As in 0-35, RX cannot be a tertiary halide, and sulfuric and sulfonic esters can be used instead of halides. As in the Williamson reaction (0-12), yields are improved by phase-transfer catalysis.753 Instead of RS ions, thiols themselves can be used, if the reaction is run in benzene in the presence of DBU (p. 1023).754 Neopentyl bromide was converted to Me3CCH2SPh in good yield by treatment with PhS in liquid NH3 at -33°C under the influence of light.755 This probably takes place by an SrnI mechanism (see p. 648). Vinylic sulfides can be prepared by treating vinylic bromides with PhS in the presence of a nickel complex,756 and with R3SnPh in the presence of Pd(PPh3)4.757 R can be tertiary if an alcohol is the substrate, e.g,758... 

In fact, the reaction of alkoxides with alkyl halides or alkyl sulfates is an important general method for the preparation of ethers, and is known as the Williamson synthesis. Complications can occur because the increase of nucleo-philicity associated with the conversion of an alcohol to an alkoxide ion always is accompanied by an even greater increase in eliminating power by the E2 mechanism. The reaction of an alkyl halide with alkoxide then may be one of elimination rather than substitution, depending on the temperature, the structure of the halide, and the alkoxide (Section 8-8). For example, if we wish to prepare isopropyl methyl ether, better yields would be obtained if we were to... 

At lower temperatures the oxonium salt or the alkyl hydrogen sulfate may react by an SN displacement mechanism with excess alcohol in the reaction mixture, thereby forming a dialkyl ether. Although each step in the reaction is reversible, ether formation can be enhanced by distilling away the ether as fast as it forms. Diethyl ether is made commercially by this process ... 

Although detailed mechanisms have not been established, the first step is thought to be formation of an unstable mixed anhydride, which then extrudes S02 and collapses with attack of chloride at the carbonyl carbon. A similar mechanism occurs in the formation of alkyl chlorides from alcohols and thionyl chloride (Section 15-5A) ... 

Addition of hydrogen sulfide and thiols is qualitatively similar to reaction with alcohols in that there are two stages, formation of hemithioacetal (or hemithio-ketal) followed by acid-catalyzed elimination of the hydroxy group and substitution of a second —SR (Equations 8.47 and 8.48). The transformation has been studied less extensively than hydration and acetal formation, and relatively little information on mechanism is available. The initial addition appears to be specific base-catalyzed, an observation that implies that RS is the species that adds. The situation is thus similar to cyanide addition. General acid catalysis has, however, been found at pH 1 to 2 for addition of weakly acidic alkyl thiols, and the reaction rate as a function of pH has a minimum and rises both on the... 

Alcohols can also be converted to alkyl halides by phosphorus halides such as PCI PBr3, and PI via an 5 2 mechanism resulting in poor yields with tertiary alcohols. Another reagent for producing alkyl halides from alcohols is thionvl chloride, OCl2, resulting in sulfur dioxide and hydrochloric acid. 

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