Acyl chlorides esterification

The mechanisms of the Fischer esterification and the reactions of alcohols with acyl chlorides and acid anhydrides will be discussed m detail m Chapters 19 and 20 after some fundamental principles of carbonyl group reactivity have been developed For the present it is sufficient to point out that most of the reactions that convert alcohols to esters leave the C—O bond of the alcohol intact... 

The acyl group of the carboxylic acid acyl chloride or acid anhydride is trans ferred to the oxygen of the alcohol This fact is most clearly evident m the esterification of chiral alcohols where because none of the bonds to the chirality center is broken m the process retention of configuration is observed... 

Esterification with acyl chlorides (Section 15 8) Acyl chlorides react with alcohols to give esters The reaction is usually carried out in the presence of pyridine... 

The most apparent chemical property of carboxylic acids their acidity has already been examined m earlier sections of this chapter Three reactions of carboxylic acids—con version to acyl chlorides reduction and esterification—have been encountered m pre vious chapters and are reviewed m Table 19 5 Acid catalyzed esterification of carboxylic acids IS one of the fundamental reactions of organic chemistry and this portion of the chapter begins with an examination of the mechanism by which it occurs Later m Sec tions 19 16 and 19 17 two new reactions of carboxylic acids that are of synthetic value will be described... 

As a dibasic acid, malic acid forms the usual salts, esters, amides, and acyl chlorides. Monoesters can be prepared easily by refluxing malic acid, an alcohol, and boron trifluoride as a catalyst (9). With polyhydric alcohols and polycarboxyUc aromatic acids, malic acid yields alkyd polyester resins (10) (see Alcohols, polyhydric Alkyd resins). Complete esterification results from the reaction of the diester of maUc acid with an acid chloride, eg, acetyl or stearoyl chloride (11). 

Esterification with carboxylic acid anhydrides (Section 15.8) Carboxylic acid anhydrides react with alcohols to form esters in the same way that acyl chlorides do. 

Section 20.7 Esters occur naturally or are prepared from alcohols by Fischer esterification or by acylation with acyl chlorides or acid anhydrides (see Table 20.3). 

As noted in the preceding section, one of the most general methods of synthesis of esters is by reaction of alcohols with an acyl chloride or other activated carboxylic acid derivative. Section 3.2.5 dealt with two other important methods, namely, reactions with diazoalkanes and reactions of carboxylate salts with alkyl halides or sulfonate esters. There is also the acid-catalyzed reaction of carboxylic acids with alcohols, which is called the Fischer esterification. 

As a historical note, SAI for Dove was made by this acyl chloride process until a commercial process for direct esterification of fatty acid and sodium isethionate was developed by Lever Brothers Co. in the late 1950 s. The SAI made by direct esterification is generally termed DEFI, an acronym for directly esterified fatty isethionate . The DEFI reaction is follows ... 

The carboxylic functionalities inserted onto the tubes can be used as platforms to obtain further transformations (Fig. 3.5). A commonly utilized route is the reaction of carboxylic groups with thionyl chloride or oxalyl chloride to prepare the corresponding acyl chlorides, which are useful intermediates for amidation or esterification reactions. Amides can also be prepared directly from the acids by means of standard solution chemistry conditions, using carbodiimide derivatives in the presence of the selected amine. 

Esterification constitutes a valuable alternative to the amidation strategy. As with amidation, the formation of the ester bond is performed following a first reaction step with acyl chloride. The ester bond has been extensively utilized to attach many organic and inorganic moieties. Porphyrins are a classic example of substrates covalently bound via esterification strategies their photoinduced electron transfer to the nanotube has been studied for applications in molecular electronics and photovoltaic devices (Fig. 3.6) [21]. 

There are several chemical reactions that can be used as an alternative to achieve covalent functionalization of CNTs. Two of them are amidation and/or esterification reactions. Both reactions take advantage of the carboxylic groups sitting on the side-walls and tips of CNTs. In particular, they are converted to acyl chloride groups (-C0-C1) via a reaction with thionyl (SO) or oxalyl chloride before adding an alcohol or an amine. This procedure is very versatile and allows the functionalization of CNTs with different entities such as biomolecules [154-156], polymers [157], and organic compounds [158,159] among others. 

When an aminoacyl-tRNA synthetase catalyzes the esterification of tRNA with an amino acid, the amino acid is activated by formation of an enzyme-bound mixed anhydride with AMP (equation 2.67) in the same way that an organic chemist activates a carboxylic acid by forming an acyl chloride or a mixed anhydride. (Note that in equation 2.67 the substrate is the magnesium complex of ATP, with the metal ion acting as an electrophilic catalyst. The Mg2+ binds primarily to the /3,y-phosphates.50 51)... 

Reactions at the carbonyl carbon—most of which involve attack by a nucleophile Nu on the carbonyl carbon with subsequent cleavage of a C-O bond. Examples are esterification, acyl chloride formation, and reduction with hydrides. 

Examples of the use of these methods are given in Expts 5.148 and 5.149. The use of an acyl chloride or acid anhydride is the method of choice for the synthesis of phenyl esters (e.g. phenyl cinnamate see also Section 9.6.6), which cannot be prepared by the direct esterification methods described above. 

Acyl chloride-functionalized SWCNTs are also susceptible to reactions with other nucleophiles, e.g. alcohols. Haddorfs group reported the preparation of soluble ester-functionalized carbon nanotubes SWCNT-COO(CH2)17CH3 (Fig. 1.6a) obtained by esterification with octadecanol [134]. The syntheses of soluble polymer-bound and dendritic ester-functionalized SWCNTs have been reported by Riggs et al. by attaching poly(vinyl acetate-co-vinyl alcohol) (Fig. 1.6b) [135] and hydrophilic and lipophilic dendron-type benzyl alcohols [119], respectively, to SWCNT-COC1 (Fig. 1.6c). These functional groups could be removed under basic and acidic hydrolysis conditions and thus additional evidence for the nature of the attachment was provided [119, 136]. 

Because the acidic hydrogen is the usual cause of undesired reactivity, carboxylic acids are commonly protected as esters. Most often, simple methyl esters are used. The ester can be prepared via the acyl chloride or by Fischer esterification (see Section 19.4). The ester group can be converted back to the carboxylic acid by hydrolysis under acidic or basic (saponification) conditions (see Section 19.5). 

The Schotten-Baumann esterification procedure is used with benzoyl chloride and other aroyl chlorides that are relatively stable to water. In this procedure the alcohol is shaken with the acyl chloride in the presence of aqueous sodium hydroxide. This method is particularly useful with phenols (Scheme 3.67). 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

Often, the carboxylic acid groups are converted to acyl chlorides with SOCI2109 110 prior to esterification with various alcohols and reaction with other nucleophiles.111 Both mono- and difunctional ester-substituted bipyridines have been generated in moderate yield by palladium(O)-catalyzed carboalkoxylation of halo- or triflate-substituted precursors in the presence of CO, an alcohol, and a tertiary amine.112... 

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