Carboxylic acid derivatives anhydrides Esters Nitriles

The six common groups derived from carboxylic acids are, in decreasing priority after carboxylic acids salts, anhydrides, esters, acyl halides, amides, and nitriles. 

This chapter concerns the preparation and reactions of acyl chlorides acid anhydrides thioesters esters amides and nitriles These com pounds are generally classified as carboxylic acid derivatives and their nomenclature is based on that of carboxylic acids... 

Closely related to the carboxylic acids and nitriles discussed in the previous chapter are the carboxylic acid derivatives, compounds in which an acyl group is bonded to an electronegative atom or substituent that can net as a leaving group in a substitution reaction. Many kinds of acid derivatives are known, but we ll be concerned primarily with four of the more common ones acid halides, acid anhydrides, esters, and amides. Esters and amides are common in both laboratory and biological chemistry, while acid halides and acid anhydrides are used only in the laboratory. Thioesters and acyl phosphates are encountered primarily in biological chemistry. Note the structural similarity between acid anhydrides and acy) phosphates. 

Formally related reactions are observed when anthracene [210] or arylole-fines [211-213] are reduced in the presence of carboxylic acid derivatives such as anhydrides, esters, amides, or nitriles. Under these conditions, mono- or diacylated compounds are obtained. It is interesting to note that the yield of acylated products largely depends on the counterion of the reduced hydrocarbon species. It is especially high when lithium is used, which is supposed to prevent hydrodimerization of the carboxylic acid by ion-pair formation. In contrast to alkylation, acylation is assumed to prefer an Sn2 mechanism. However, it is not clear if the radical anion or the dianion are the reactive species. The addition of nitriles is usually followed by hydrolysis of the resulting ketimines [211-213]. 

Carboxylic acid derivatives are compounds that possess an acyl group (R—C=0) linked to an electronegative atom, e.g. —Cl, —CO2 R, —OR or —NH2. They can be converted to carboxylic acids via simple acidic or basic hydrolysis. The important acid derivatives are acid chlorides, acid anhydrides, esters and amides. Usually nitriles are also considered as carboxylic acid derivatives. Although nitriles are not directly carboxylic acid derivatives, they are conveniently hydrolysed to carboxylic acids by acid or base catalysts. Moreover, nitriles can be easily prepared through dehydration of amides, which are carboxylic acid derivatives. 

Because C-H bonds are usually less reactive towards dioxirane oxidation than heteroatoms and C-C multiple bonds, it is instructive to give a few general guidelines on the compatibility of functional groups within the substrate to be submitted to oxidative C-H insertion Substances with low-valent heteroatoms (N, P, S, Se, I, etc.), C-C multiple bonds, and C=X groups (where X is a N or S heteroatom) are normally not suitable for C-H insertions, because these functionalities react preferably. Even heteroarenes are more susceptible to dioxirane oxidation than C-H bonds, whereas electron-rich and polycyclic arenes are only moderately tolerant, but electron-poor arenes usually resist oxidation by dioxiranes. N-oxides and N-oxyl radicals are not compatible because they catalyze the decomposition of the dioxirane. Oxygen insertion into Si-H bonds by dioxirane is more facile than into C-H bonds and, therefore, silanes are not compatible. Substance classes normally resistant towards dioxirane oxidation include the carboxylic acids and their derivatives (anhydrides, esters, amides, and nitriles), sulfonic acids and their de-... 

This reagent also reduces nitro, nitrile, and amide derivatives to amines, and carboxylic acids and anhydrides to alcohols. The yields of these reductions arc nearly quantitative. Esters and halobenzene derivatives are not reduced. 

L22,13 and L24.12,14 Many carboxylic acid derivatives such as esters, amides, and chlorides or anhydrides may also be used. The same reaction conditions can be applied to the condensation reaction of aromatic nitriles with o-phenylenediamine for the synthesis of H2L8,15 H2L13, and L13a.16,17... 

Carboxylic acid chlorides. See Acyl chlorides Carboxylic acid derivatives, 774—830. See also Acyl chlorides Amides Carboxylic acid anhydrides Esters Nitriles... 

Carboxylic acid derivatives are compounds with functional groups that can be converted to carboxylic acids by a simple acidic or basic hydrolysis. The most important acid derivatives are esters, amides, and nitriles. Acid halides and anhydrides are also included in this group, although we often think of them as activated forms of the parent acids rather than completely different compounds. 

This chapter will discuss methods for the preparation of esters, acid chlorides, anhydrides, and amides from carboxylic acids, based on acyl substitution reactions. Acyl substitution reactions of carboxylic acid derivatives will include hydrolysis, interconversion of one acid derivative into another, and reactions with strong nucleophiles such as organometallic reagents. In addition, the chemistry of dicarboxylic acid derivatives will be discussed, as well as cyclic esters, amides, and anhydrides. Sulfonic acid derivatives will be introduced as well as sulfate esters and phosphate esters. Finally, nitriles will be shown to be acid derivatives by virtue of their reactivity. 

We did not see a method for directly converting a carboxylic acid into either an amide or a nitrile. All other carboxylic acid derivatives (acid chlorides, acid anhydrides, and esters) can be made directly from a carboxylic acid. 

The most direct synthesis of 2-acylbenzo[6]thiophenes involves reaction of the readily available 2-lithio derivative with acylating agents, such as nitriles, acid anhydrides, etc. (equation 19). Benzo[f>]thiophene-2-carboxylic acids are available by a variety of cyclization reactions (Section 3.15.9.2.4) and the acid chlorides or esters can be used to synthesize 2-acyl derivatives by conventional means. 

Thermal dehydration of o- (acylamino)phenols is the method of choice for the preparation of benzoxazoles (equation 96) and other annulated oxazoles. 0,iV-Diacyl derivatives of o-aminophenols cyclize at lower temperatures than do the monoacyl compounds. The synthesis is often carried out by heating the aminophenol with the carboxylic acid or a derivative, such as the acid chloride, anhydride, an ester, amide or nitrile. The Beckmann rearrangement of oximes of o-hydroxybenzophenones leads directly to benzoxazoles (equation 97). 

This chapter includes not only nuclear and extranuclear pyrazinecarboxylic acids and anhydrides, but also the related esters, acyl halides, amides, hydrazides, nitriles, aldehydes, ketones, and any of their thio analogues a few rare isothiocyanatopy-razines and pyrazinecarbonitrile oxides are also included. To avoid repetition, interconversions of these pyrazine derivatives are discussed only at the first opportunity for example, the esterification of carboxylic acids is discussed as a reaction of carboxylic acids rather than as a preparative route to carboxylic esters, simply because the section on carboxylic acids precedes that on carboxylic esters. To minimize any confusion, many cross-references have been inserted. 

Hydrolysis of acid chlorides, acid anhydrides, esters and carboxamides leads to the carboxylic acid, although these compounds are often derived from a carboxylic acid group in the first place (Scheme 5.5). Nitriles are usually derived from amines via diazotization and reaction with copper(I) cyanide (see Chapter 8) and so the hydrolysis of a nitrile group is of more value. In all cases, alkaline hydrolysis gives the salt of the acid, from which the free acid is obtained by addition of mineral acid. 

This chapter is concerned with the cathodic reduction of carboxylic acids and their derivatives, that is, esters, amides, anhydrides, acyl halides, hydrazides, nitriles, and corresponding thio derivatives. Cyclic derivatives of substituted carboxylic and polycarboxylic acids, such as lactones, lactams, imides, and anhydrides, are also included. Only those transformations in which the functional group itself is involved are discussed. Reductive coupling of carboxylic acids and derivatives is covered in Chapter 22, and there is some overlap with reduction of heterocycles in Chapter 18. 

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