Alcohols free carboxylic acids

Expulsion of alcohol yields the free carboxylic acid product and regenerates the acid catalyst. 

Because Me3SiCl 14 is almost inert to lithium organic compounds or Grignard reagents in non-polar solvents, formation of tertiary alcohols on addition of MeLi or n-BuLi to free carboxylic acids [127] or their methyl or ethyl esters [128] in THF... 

Polycarboxylated polyalkoxylates and their sulfate derivatives may be prepared by reacting an ethoxylated or propoxylated alcohol with a water-soluble, alkali or earth alkali metal salt of an unsaturated carboxylic acid [339]. The reaction occurs in aqueous solution in the presence of a free radical initiator and gives products of enhanced yield and reduced impurity levels, compared with the essentially anhydrous reactions with free carboxylic acids, which have been used otherwise. The method provides products that give solutions that are clear on neutralization, remain clear and homogeneous on dilution, and are useful as cleaning agents in drilling and other oil field operations. 

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

Scheme 25.—Photochemical Release of Free Carboxylic Acid from a 2-Nitrobenzyl-substituted Poly(vinyl Alcohol).

Esters of 2-(2-azidophenyl)ethyl alcohol are photolyzed under a high-pressure mercury lamp to a reactive nitrene intermediate which, following insertion into the alkyl side-chain, undergoes elimination to give the free carboxylic acid (up to 32%) and producing indole. The photochemical release was somewhat improved (65-80%) when 5-azido-4-(hydroxy-methyl)-l-methoxy naphthalene was used (see Scheme 27). 

Use of ruthenium catalysts [41] and rhenium heptoxide [42] is rare. Their specialty is reduction of free carboxylic acids to alcohols. 

Free acids require still an additional hydride equivalent because their acidic hydrogens combine with one hydride ion of lithium aluminum hydride forming acyloxy trihydroaluminate ion. Complete reduction of free carboxylic acids to alcohols requires 0.75 mol of lithium aluminum hydride. The same amount is needed for reduction of monosubstituted amides to secondary amines. Unsubstituted amides require one full mole of lithium aluminum hydride since one half reacts with two acidic hydrogens while the second half achieves the reduction. 

Reduction of aromatic carboxylic acids to alcohols can be achieved by hydrides and complex hydrides, e.g. lithium aluminum hydride 968], sodium aluminum hydride [55] and sodium bis 2-methoxyethoxy)aluminum hydride [544, 969, 970], and with borane (diborane) [976] prepared from sodium borohydride and boron trifluoride etherate [971, 977] or aluminum chloride [755, 975] in diglyme. Sodium borohydride alone does not reduce free carboxylic acids. Anthranilic acid was reduced to the corresponding alcohol by electroreduction in sulfuric acid at 20-30° in 69-78% yield [979],... 

Complete reduction of acyl chlorides to primary alcohols is not nearly as important as the reduction to aldehydes since alcohols are readily obtained by reduction of more accessible compounds such as aldehydes, free carboxylic acids or their esters [83,968]. Because aldehydes are the primary products of the reduction of acyl chlorides strong reducing agents convert acyl chlorides directly to alcohols. 

A process based on the use of an immobilized C. antarctica lipase (Novozym 435) has been developed in order to perform direct esterification of natural alcohols with carboxylic acids in a solvent-free system. Based on the system represented in Figure 11.2, the process had to overcome the problem of recycling the nitrogen, once the reaction was over. 

The next structural formula illustrates the course of a transesterification which proceeds smoothly and quickly if it is catalyzed with soluble aluminum salts found in the reaction medium, for instance, with basic aluminum stearate. In contrast to the conventionally catalyzed transesterifications by alkali alcoholate, the presence of free carboxylic acid does not have a negative effect. The catalyst... 

Consider the formation of an ester (or of an amide) from a free carboxylic acid and an alcohol (or amine) by elimination of a molecule of water (Eq. 17-35). 

Acidic Hydrolysis. Hydrolysis of esters by use of water and a mineral acid leads to an equilibrium mixture of ester, alcohol, and free carboxylic acid. Complete reaction can only be achieved by removal of alcohol or acid from the equilibrium. Because esters have poor solubility in water, the reaction rate in dilute acids is fairly low. Therefore, emulsifiers such as sulfonated oleic acid or sulfonated aromatic compounds (Twitchell reagent) are added to facilitate the reaction. 

It is possible to oxidize alcohols in the presence of free carboxylic acids.206 Nevertheless, sometimes better results are obtained if the acid is protected, for example by methylation.207 Sometimes, free carboxylic acids have a low solubility in cold CH2C12. In such cases, an in situ protection with the silylating agent, bis(trimethylsilyl)acetamide (BSA) normally allows the solubilization of the acid as trimethylsilyl ester, and an easy Swern oxidation. The resulting silylated acid is easily deprotected during the work-up.208... 

Normally, it is possible to perform selective oxidation of allylic and benzylic alcohols with M11O2 in the presence of free carboxylic acids.54 a-Hydroxycarboxylic acids suffer an oxidative breakage on contact with active Mn02.55... 

Asymmetric aikyiation of imide etiolates.1 The sodium enolates of 3 and 7 are alkylated with marked but opposite diastereoselectivity by alkyl halides. The selectivity is improved by an increase in the size of the electrophile, with methylation being the least stereoselective process. The asymmetric induction results from formation of (Z)-enolates (chelation) with the diastereoselectivity determined by the chirality of the C4-substituent on the oxazolidone ring (equations I and II). The products can be hydrolyzed to the free carboxylic acids or reduced by LiAlH4 to the corresponding primary alcohols and the unreduced oxazolidone (1 or 2). 

Many compounds will undergo dimerization reactions those containing thiols (e.g., disulfide formation) olefins, alcohols, and carboxylic acids (or other carbonyl chemistry e.g., aldol condensation reactions). Indoles have been shown to dimerize under acidic conditions. The dimerization is presumed to occur as shown in Figure 120 via protonation at C3 and nucleophilic attack of a second indole on C2. Phenols have been shown to dimerize under free radical initiated oxidative conditions, usually to ortho phenols. Nalidixic acid API undergoes dimerization under thermolysis conditions to decarboxylate and produce a dimeric structure (Fig. 121) (172). 

Hydrolytic enzymes such as lipases and proteases catalyze readily reversible reactions and will often promote reverse hydrolysis at reduced water activities. Water can be removed with desiccants, as an azeotrope with a solvent or through application of a vacuum. Lipases have proven particularly useful in this regard, allowing the formation of esters from alcohols and either free carboxylic acids or esters (see Figure 31.12). 

Elimination of carbon dioxide from carboxyl, water from alcoholic hydroxyl, carboxylic acid from alkanoate, and hydrogen chloride from chlorine side groups or chain ends are typical thermal decomposition reactions in the temperature range 250-350°C. Hydrogen chloride is an important product of poly(vinyl chloride) because every second carbon atom of the hydrocarbon polymer chain is chlorine substituted. But hydroxyl, alkanoate and free carboxylic acid groups normally occur only at the ends of the macromolecular chains in customary plastics, thus the contribution of their elimination to the volatile pyrolysis products is negligible. 

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