Esters reactions with alcohol

Zn, TiCl4, CH2Br2, THF, CH2CI2 methylenation of aldehydes, ketones no reaction with esters, THP-ethers, TBS-ethers, carboxylic acids, alcohols [716,717]... 

While the alkyl group switching reaction is not observed in the gas phase, secondary and tertiary alcohols give rise to a totally different reaction with esters. Typical examples are shown in (79) and (80). These reactions display a reverse reactivity compared to the acids, viz., t-C4H9OH > i-C3H7OH > primary alcohols (Table 9). In fact, these reactions have not been detected for primary alcohols. 

The reactions of Grignard reagents with aldehydes and ketones give alcohols, reaction with acid chlorides and esters give tertiary alcohols, reaction with carbon dioxide to give carboxylic acids, reaction with nitriles give ketones, and reaction with epoxides give alcohols. 

Ester synthesis (acid + alcohol) Reaction preferably with primary alcohols Reaction with primary and secondary alcohols... 

It should finally be pointed out that trimethylsilyl ethers can also be transformed directly into other functionalities. Oxidation with NBS leads to ketones and aldehydes, treatment with LiAllWAlCb results in deoxygenation of the alcohol, reaction with carboxylic acid anhydrides in the presence of BF3-OEt2 produces esters and on treatment with PhsP Brj acid bromides are foimed directly from TMS esters. ss... 

Alcohol derivatives 1.155 (Y = CHOHR) are useful as auxiliaries in a-keto-ester reductions [540] or [4+2] cycloadditions of aciylates [548]. 6-Lactams are obtained from imines 1.155 (Y = CH=NAr) with a high enantiomeric excess after reaction with ester enolates and decomplexation [549]. Alkylations of benzylimine 1.155 (Y = Ph2N=CH) give interesting results [539], and some 1,3-dipdar cycloaddition reactions with nitrones have been described [550],... 

Benzil, 4,4 -bis(di- -propylamino)-, 41, 3 Benzoic acid, dithio-, carboxymethyl ester, 42,100 Benzopyrazole, 42, 69 N-Benzylacetamide, 42,18 n-Benzylacrylamide, 42,16 Benzyl alcohol, reaction with acrylonitrile, 42,16... 

Virtually all of the vast number of methanesulfonate, or mesylate , esters prepared to facilitate elimination or substitution of a hydroxyl function have been prepared from sulfene the standard procedure using methanesulfonyl chloride and triethylamine in dichloromethane has been described by Crossland and Servis138. To be sure, sulfene intermediacy is not required for alkanesulfonate ester formation the reaction, as has been noted (in Section IV.A.2), will proceed without base promotion via the direct displacement route, but it is usually sufficiently sluggish, however, that the further reaction of the ester with the alcohol competes with ester formation139. This makes the procedure a poor one for most practical purposes, although we recently encountered an instance, namely the preparation of neopentyl 2-chloroethanesulfonate87, in which the direct reaction of the alcohol and sulfonyl chloride without base was the method of choice this arose because (a) the product is stable and (b) 2-chloroethanesulfonyl chloride does not yield the corresponding sulfene with tertiary amines (Section IV.A.2). 

The reversible reaction of alcohols and carboxylic acids to make organic esters is presented here only to alert you to Ihe major connection alcohols have with esters. Esters arc the most common and most important carboxylic acid derivatives, and their chemistry will be explored in dolail in. several places during the last third of the course. 

Compound 310 has been used in a stereoselective synthesis of (iS)-4,5-dihydro-4-methyl-2(3//)turanone (315) (Scheme 42), an important chiral building block. After reduction of the ester, protection of the primary alcohol, removal of the EE group, and tosylation of the secondary alcohol, reaction with di- er butyl malonate gives 313 with 97% inversion of configuration [107]. Hydrolysis, debenzylation, lactonization, and decarboxylation furnishes the product 315 (93% ee). 

Secondary and tertiary alcohols can be prepared by reacting a Grignard reagent with aldehydes and ketones, respectively, but these are not the only electrophiles that can be used with a Grignard. Grignards also have useful reactions with esters and epoxides. These reactions also give alcohol products, but they lead to alternate retrosynthetic strategies for certain alcohol TMs. 

Notes The reaction is suitable for the detection of alcohols of Cs and higher. A positive reaction is also given by hydroaromatic alcohols, phenols, and all compoimds with a double bond in the chain or in the ring, as well as compounds with a three-membered ring. Some ketones (acetone, methyl ethyl ketone, cyclohexanone) and aldehydes (acetaldehyde, propionaldehyde, isovaleraldehyde) also react positively. As regards the reaction with esters of acids and glycols, the data in the literature are conflicting. 

The reaction with sodium is by no means an infallible practical test for alcohols since, strictly speaking, it is applicable only to pure anhydrous liquids. Traces of water, present as impurities, would give an initial evolution of hydrogen, but reaction would stop after a time if an alcohol is absent furthermore, certain esters and ketones also evolve hydrogen when treated with sodium (compare Section XI,7,6). It may, however, be assumed that if no hydrogen is evolved in the test, the substance is not an alcohol. 

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