Alcohols preparation from carboxylic acids

Esters are usually prepared from carboxylic acids by the methods already discussed. Thus, carboxylic acids are converted directly into esters by SK2 reaction of a carboxyfate ion with a primary alkyl halide or by Fischer esterification of a carboxylic acid with an alcohol in the presence of a mineral acid catalyst. In addition, acid chlorides are converted into esters by treatment with an alcohol in the presence of base (Section 21.4). 

Table 3-1. Monoesters prepared from carboxylic acids and alcohols or phenols using AyV -carbonyldiimid-azole (CDI), N-acylimidazole (RCOIm), or AyV -sulfinyldiimidazole (ImSOIm).

Table 3-2. Diesters prepared from carboxylic acids and alcohols using A -carbonyldiimidazole (CDI).

The esterification of support-bound carboxylic acids has not been investigated as thoroughly as the esterification of support-bound alcohols. Resin-bound activated acid derivatives that are well suited to the preparation of esters include O-acylisoureas (formed from acids and carbodiimides), acyl halides [23,226-228], and mixed anhydrides (Table 13.15). A-Acylurea formation does not compete with esterifications as efficiently as it does with the formation of amides from support-bound acids. Esters can also be prepared from carboxylic acids on insoluble supports by acid-catalyzed esterification [152,229]. Alternatively, support-bound carboxylic acids can be esteri-fied by O-alkylation, either with primary or secondary aliphatic alcohols under Mitsu-nobu conditions or with reactive alkyl halides or sulfonates (Table 13.15). 

Support-bound isocyanates can be conveniently prepared from carboxylic acids by Curtius degradation. Because the reaction of the intermediate acyl azides with alcohols to yield esters is slow, Curtius degradation can be conducted in the presence of alcohols to yield carbamates directly (Entries 4 and 5, Table 14.8). 

Esters can be prepared from carboxylic acids and alcohols provided an acidic catalyst is present,... 

Esters of tertiary alcohols may not be prepared from carboxylic acids containing acidic a-protons using this modified procedure, since deprotonation and subsequent condensation, competes. However, the use of stoichiometric 1,8-Diazabicyclo[5.4.0]-undec-7-ene as base has been shown to provide good yields of i-butyl esters even for acids with acidic a-protons (eq 3). This procedure was unsuccessful for pivaUc acid or for IV-acyl-a-amino acids. 

Esters can be prepared by acid-catalyzed esterification or by reaction of the acid chloride with the alcohol. In small-scale syntheses, it is often more convenient to prepare the ester by reaction of the carboxylic acid with the appropriate diazo compound. Diazomethane is routinely used for making methyl esters, but more highly substituted esters can be prepared if the corresponding diazo compound is available. Benzhydryl esters, for example, are readily prepared from carboxylic acids by reaction with diphenyldiazomethane ... 

The structure and nomenclature of sulfonate esters (see 113, 114, or 115) are described in Chapter 20 (Section 20.11.2). It is also true that sulfonate esters are good leaving groups in the substitution reactions described in this chapter (see Section 11.2.4). Sulfonate esters are prepared by the reaction of sulfonic acids with alcohols—much the way that carboxylic acid esters are prepared from carboxylic acids and alcohols (described in Chapter 20, Section 20.11.2). More commonly, sulfonate esters are prepared by the reaction of a sulfonyl chloride (see 112) with an alcohol. This reaction is also described in Chapter 20. This section presents only a simple preview of that chemistry, with the goal of showing that it is easy to convert alcohols into sulfonate esters, which are then useful as leaving groups in substitution reactions. The formal mechanism of these reactions will be discussed in Chapter 20. 

Esters are prepared from carboxylic acids by the reaction between an acid chloride and an alcohol or between a carboxylic acid and an alcohol under acidic conditions. Both sulfonic acids and sulfonyl chlorides react with alcohols to form sulfonate esters. When butanesulfonyl chloride (177) reacts with propanol, usually in the presence of a base such as triethylamine, propyl butanesulfonate (180) is formed. A wide range of sulfonyl esters can be formed this way from an alcohol and a sulfonic acid. 

The reaction of trivalent carbocations with carbon monoxide giving acyl cations is the key step in the well-known and industrially used Koch-Haaf reaction of preparing branched carboxylic acids from al-kenes or alcohols. For example, in this way, isobutylene or tert-hutyi alcohol is converted into pivalic acid. In contrast, based on the superacidic activation of electrophiles leading the superelectrophiles (see Chapter 12), we found it possible to formylate isoalkanes to aldehydes, which subsequently rearrange to their corresponding branched ketones. 

Me3SiCH2CH=CH2i TsOH, CH3CN, 70-80°, 1-2 h, 90-95% yield. This silylating reagent is stable to moisture. Allylsilanes can be used to protect alcohols, phenols, and carboxylic acids there is no reaction with thiophenol except when CF3S03H is used as a catalyst. The method is also applicable to the formation of r-butyldimethylsilyl derivatives the silyl ether of cyclohexanol was prepared in 95% yield from allyl-/-butyldi-methylsilane. Iodine, bromine, trimethylsilyl bromide, and trimethylsilyl iodide have also been used as catalysts. Nafion-H has been shown to be an effective catalyst. 

This tertiary ester was developed to reduce aspartimide and piperidide formation during the Fmoc-based peptide synthesis by increasing the steric bulk around the carboxyl carbon. A twofold improvement was achieved over the the standard Fbutyl ester. The Mpe ester is prepared from the acid chloride and the alcohol and can be cleaved under conditions similar to those used for the r-butyl ester. ... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

The classification is unaffected by allylic, vinylic, or acetylenic unsaturation appearing in both starting material and product, or by increases or decreases in the length of carbon chains for example, the reactions f-BuOH f-BuCOOH, PhCHgOH - PhCOOH, and PhCH=CHCH20H -PhCH=CHCOOH would all be considered as preparations of carboxylic acids from alcohols. Conjugate reduction and alkylation of unsaturated... 

The main drawback to this reaction is the toxicity of diazomethane and some of its precursors. Diazomethane is also potentially explosive. Trimethylsilyldia-zomethane is an alternative reagent,42 which is safer and frequently used in preparation of methyl esters from carboxylic acids.43 Trimethylsilyldiazomethane also O-methylates alcohols.44 The latter reactions occur in the presence of fluoroboric acid in dichloromethane. 

Due to excellent yields, mild reaction conditions, and a fast reaction rate, the azolide method is well suited to the synthesis of isotopically labeled esters, even ones with very short half-lives, just as it is always useful for the esterification of sensitive carboxylic acids, alcohols, and phenols under mild conditions. An example is provided by the synthesis of [nC]-quinuclidinyl benzilate prepared from benzilic acid, CDI, and nC-labeled quinuclidinol.[147]... 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

Preparation of carboxylic esters from carboxylic acids and alcohols H+ R-C-OH + R OH R-C-OR +H20 II II 0 0... 

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (see Section 5.5.5). 

Esters, RC02R, are named as salts are the R group is named first, followed by the name of the carboxylate group (for example, CH3CO2CH2CH3 is ethyl acetate). Esters can be prepared from an acid and an alcohol, with a mineral acid catalyst (Fischer esterification). The key step of the mechanism is nucleophilic attack by the alcohol on the protonated carbonyl group of the acid. Many esters are used as flavors and perfumes. 

Vapor pressure selectivity and other phase-specific reactions might be useful for achieving selectivity not possible by conventional means. The method makes reactive radicals such as H atoms available in preparatively useful amounts using only inexpensive apparatus. Alkanes can be functionalized in a variety of ways. Several unusual compounds are also available in this way from a variety of alcohols, alkenes, amines, carboxylic acids, ethers, and fluorocarbons. 

Examples of alkylation, dealkylation, homologation, isomerization, and transposition are found in Sections 1, 17, 33, and so on, lying close to a diagonal of the index. These sections correspond to such topics as the preparation of acetylenes from acetylenes carboxylic acids from carboxylic acids and alcohols, thiols, and phenols from alcohols, thiols, and phenols. Alkylations that involve conjugate additions across a double bond are found in Section 74 (alkyls, methylenes, and aryls from olefins). 

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