Alkylation by alcohols

Compounds containing active methylene groups can be alkylated by alcohols with loss of hydrogen from that position. For example, in the presence of boron trifluoride, isopropyl alcohol and ethyl acetoacetate give ethyl 2-iso-propylacetoacetate in 60-70% yield 643 the isopropyl group can be introduced in the same way into acetylacetone (2,4-pentanedione) 644 and reactions of xanthhydrol with malonic esters have also been recorded in the literature.645 

The loss of the elements of water between an alcohol and an aromatic hydrocarbon is a smooth reaction, particularly when the alcohol is of benzyl type or an alkanol with a chain length of at least three carbon atoms (see also page 970). 

Benzyl alcohol and benzene in a mixture of glacial acetic acid and sulfuric acid give diphenylmethane even at room temperature,646 and diphenyl-methanol gives an almost theoretical yield of diphenyl-p-tolylmethane when boiled with toluene and phosphoric oxide 647 diphenylacetic acid is formed in yields up to 96% on reaction of mandelic acid with benzene in the presence of aluminum chloride.648 

In such reactions aliphatic alcohols do not give straight-chain products branched-chain compounds are always produced, as in Friedel-Crafts syntheses with alkyl chlorides. Various alkylaromatic compounds are produced 

Cumene Benzene (50g) is heated with isopropyl alcohol (19 g) and 80% sulfuric acid (400 ml) for 3-4 h at 65°. The usual working up then gives a 65 % yield of cumene. 

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Reductive alkylation by alcohol solvents may occur as an unwanted side reaction 22,39), and it is to avoid this reaction that Freifelder (20) recom mends ruthenium instead of nickel in pyridine hydrogenation. Alkylation by alcohols may occur with surprising ease 67). Reduction of 18 in ethanol over 10% palladium-on carbon to an amino acid, followed bycyclization with /V,/V-dicyclohexylcarbodiimide gave a mixture of 19 and 20 wiih the major product being the /V-ethyl derivative 49,50). By carrying out the reduction in acetic acid, 20 was obtained as the sole cyclized product 40). 

Alkylations. The 0-alkylation of ai MTO, and thus, both symmetrical and uns>i are also alkylated by alcohols. 

C-Alkylations. Triethyl methanetricarboxylate is readily alkylated by alcohols. Propargylic alcohols are homologated to give 3-alkynenitriles with acetone cyanohydrin to supply the cyano group. ... 

With sulphuric acid, phenols are readily alkylated by alcohols and olefins (12.273), and with pyridine carbodiitnides can be prepared (12.274). 

The alkoxide pathway occurs by initial insertion of CO into a palladium alkoxide, followed by insertion of the alkene into the bond between the metal and the alkoxycarbonyl group to form a paUadium-alkyl complex (Scheme 17.18). Protonation of this metal alkyl by alcohol would form the free organic product and regenerate the paUadium alkoxide. This mechanism has now been ruled out for the reactions of ethylene to form methyl propanoate. Although each of these steps has precedent, the absence of reduction products from the alkoxide argues against this pathway. Moreover, the alkyl generated from insertion of ethylene into the palladium-alkoxycarbonyl complex (Scheme 17.18) is chelated to the metal, and metha-nolysis of this species is slower than the steps of the alternative hydride mechanism. ... 

Some of the most commonly reported C-alkylation methods involving the transition-metal-catalyzed transfer hydrogenation of alcohols can be described as follows (1) the a-alkylation of ketones and carbonyl compounds (2) alcohol-alcohol coupling reactions to afford ketones and (3) P-alkylation by alcohol dimerization, which is also referred to as a Guerbet reaction. 

Scheme 5 Metal-catalyzed ( -alkylation by alcohol dimerization (Guerbet reaction)...

Koren AO, Gaponik PN (1990) Regioselective of tetrazole and 5-substituted tetrazoles N2 alkylation by alcohols. Chem Heterocycl Compd 26 1366-1370... 

Both Ir and Ru NHC eomplexes were successfully used for transfer-hydrogenation reactions, wherein an alcohol or amine is oxidized, followed by reaction of the oxidized species and hydrogenation to give the final product. Both Crabtree and Peris reported the use of Ir carbene complexes as catalysts in reactions of this type, sueh as the A -alkylation by alcohols (Equations... 

Thiourea has been S-alkylated by alcohols. By refluxing mixtures of thiourea and a primary or secondary alcohol with toluene-p-sulphonic acid in dioxan, Nakano and his co-workers obtained salts of the type (321)." Thiols were produced by the basic hydrolysis of these salts." ... 

A special apparatus (Fig. Ill, 40,1) renders the preparation of iodides from alcohols a very simple operation. The special features of the apparatus are —(i) a wide bored (3-4 mm.) stopcock A which considerably reduces the danger of crystallisation in the bore of the tap of the iodine from the hot alcoholic solution (ii) a reservoir B for the solid iodine and possessing a capacity sufficiently large to hold all the alkyl iodide produced (iii) a wide tube C which permits the alcohol vapour fix)m the flask D to pass rapidly into the reservoir B, thus ensuring that the iodine is dissolved by alcohol which is almost at the boiling point. An improved apparatus is shown in Fig. Ill, 40, 2, a and b here a... 

Picrates of p-naphthyl alkyl ethers. Alkyl halides react with the sodium or potassium derivative of p-naphthol in alcoholic solution to yield the corresponding alkyl p-naphthyl ethers (which are usually low m.p. solids) and the latter are converted by alcoholic picric acid into the crystalline picrates ... 

The mono-alkyl malonic ester may be hydrolysed by alcoholic potassium... 

Protonolysis. Simple trialkylboranes are resistant to protonolysis by alcohols, water, aqueous bases, and mineral acids. In contrast, carboxyUc acids react readily with trialkylboranes, removing the first alkyl group at room temperature and the third one at elevated temperatures. Acetic and propionic acids are most often used. The reaction proceeds with retention of configuration of the alkyl group via a cycHc, six-membered transition state (206). 

The uses of propylene may be loosely categorized as refinery or chemical purpose. In the refinery, propylene occurs in varying concentrations in fuel-gas streams. As a refinery feedstock, propylene is alkylated by isobutane or dimerized to produce polymer gasoHne for gasoHne blending. Commercial chemical derivatives include polypropylene, acrylonitrile, propylene oxide, isopropyl alcohol, and others. In 1992, ca 64% of U.S. propylene suppHes were consumed in the production of chemicals (74). Polypropylene has been the largest consumer of propylene since the early 1970s and is likely to dominate propylene utilization for some time. 

Pyrrohdinone can be alkylated by reaction with an alkyl haUde or sulfate and an alkaline acid acceptor (63,64). This reaction can be advantageously carried out with a phase-transfer catalyst (65). Alkylation can also be accompHshed with alcohols and either copper chromite or heterogenous acid catalysts... 

The hetero ring in 4-(l -hydroxyalkylidene)-5-oxazolones is cleaved by alcoholic HCl to form alkyl a-acylaminoacylacetates, which cyclize to oxazole-4-carboxylates [Eq. (25)]. This rearrangement occurs directly in alkali, and a carbon-14 tracer study has substantiated a mechanism involving ring opening followed by the alternative ring closure. ... 

Thiols, the sulfur analogs of alcohols, are usually prepared by Sjv 2 reaction of an alkyl halide with thiourea. Mild oxidation of a thiol yields a disulfide, and mild reduction of a disulfide gives back the thiol. Sulfides, the sulfur analogs of ethers, are prepared by an Sk2 reaction between a thiolate anion and a primary or secondary alkyl halide. Sulfides are much more nucleophilic than ethers and can be oxidized to sulfoxides and to sulfones. Sulfides can also be alkylated by reaction with a primary alkyl halide to yield sulfonium ions. 

This reaction is illustrative of a general procedure for the alkylation of active methylene functions in the presence of concentrated aqueous alkali catalyzed by tetraalkylammonium salts. This catalytic method has been used to alkylate arylacetonitriles with monohaloalkanes,2 dihaloalkanes,3 a-chloroethers,4 chloronitriles,.5 haloacetic acid esters,6 and halonitro aromatic compounds.7 It has also been used to alkylate ketones,8 lf/ indene,9 9i/-fluorene,ll) and the Reissert compound.11 The reaction is inhibited by alcohols and by iodide ion.2... 

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