Other Carboxylic Acid Derivatives

There has been little success with derivatives other than the unsaturated ones referred to above. The main exception is with amino adds, which, as discussed later, are very successful coupling agents for nanolayer silicates into some polyamides. There has also been some interest in hydroxy adds, such as hydroxy stearic add and its derivatives. The main use for these products currently seems to be as high-efficiency dispersants, espedally for inorganic pigments. 

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Conversion of Acyl Chlorides to Other Carboxylic Acid Derivatives... 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

Mechanistically amide hydrolysis is similar to the hydrolysis of other carboxylic acid derivatives The mechanism of the hydrolysis m acid is presented m Figure 20 7 It proceeds m two stages a tetrahedral intermediate is formed m the first stage and disso ciates m the second... 

Esters undergo the same kinds of reactions that we ve seen for other carboxylic acid derivatives, but they are less reactive toward nucleophiles than either acid chlorides or anhydrides. All their reactions are equally applicable to both acyclic and cyclic esters, called lactones. 

Conversion of Amides into Amines Reduction Like other carboxylic acid derivatives, amides can be reduced by LiAlH.4. The product of the reduction, however, is an amine rather than an alcohol. The net effect of an amide reduction reaction is thus the conversion of the amide carbonyl group into a methylene group (C=0 —> CTbV This kind of reaction is specific for amides and does not occur with other carboxylic acid derivatives. 

Mlerenes at 6 pM and white light to produce growth inhibition in human HeLa cancer cells. However, these same authors later reported that other carboxylic acid derivatives of C60 and C70 were completely without any photoactivity as PDT agents at 50pM (Irie et al., 1996). 

Amides behave differently towards LAH than the other carboxylic acid derivatives, and the overall reaction observed is reduction of the carhonyl to a methylene group, with retention of the amino group. 

As befits the euhauced uucleophilicity of hydroxylamiues (cf. the a effect), the reactiou of hydroxylamiue itself with esters, aud a variety of other carboxylic acid derivatives, readily produce the correspoudiug hydroxamic acid (equatiou 4),... 

Amides are the least reactive carboxylic acid derivatives, and are easily obtained from any of the other carboxylic acid derivatives. Carboxylic acids react with ammonia and 1° and 2° amines to give 1°, 2° and 3° amides. 

Acid chlorides are easy to reduce than carboxylic acids and other carboxylic acid derivatives. They are reduced conveniently all the way to 1° alcohols by metal hydride reagents (NaBH4 or LiAlH4), as well as by catalytic hydrogenation (H2/Pd—C). 

Amides, azides and nitriles are reduced to amines by catalytic hydrogenation (H2/Pd—C or H2/Pt—C) as well as metal hydride reduction (LiAlH4). They are less reactive towards the metal hydride reduction, and cannot be reduced by NaBITj. Unlike the LiAlIU reduction of all other carboxylic acid derivatives, which affords 1° alcohols, the LiAlIU reduction of amides, azides and nitriles yields amines. Acid is not used in the work-up step, since amines are basic. Thus, hydrolytic work-up is employed to afford amines. When the nitrile group is reduced, an NH2 and an extra CH2 are introduced into the molecule. 

In summary, therefore, the detailed mechanism of the hydrolysis of carboxylic anhydrides is still in doubt and we must hope for further experimental evidence to clarify the position. As for the hydrolysis of the other carboxylic acid derivatives dealt with in this chapter, none of the mechanistic criteria, that have been used to interpret the kinetic data, gives an unambiguous interpretation, resulting in a situation where details of mechanism are open to argument. This is particularly the case for solvolysis reactions where uncertainty as to the structure and effect of the solvent preclude a firm assignment of transition state structures. This is not to say that the mechanisms are not... 

Numerous solid-phase preparations of quinazolinones have been reported. The main synthetic strategies used are summarized in Figure 15.16. Quinazolin-2,4-diones can be prepared from anthranilic acid derived ureas or from N-(alkoxycarbonyl)-anthranilamides. These reactions have been performed on insoluble supports either in such a way that the cyclized product remains linked to the support, or such that it is simultaneously cleaved from the support upon ring formation. Quinazolin-4-ones can be prepared by cyclocondensation of anthranilamides with aldehydes, orthoesters [342], or other carboxylic acid derivatives [343]. The selection of examples listed in Table 15.29 illustrates the variety of substitution patterns accessible by means of these cyclizations. 

A particularly large a effect of about 33 ppm characterizes the carboxylic acid chloride function [317], while the fi and y effects are similar to those of other carboxylic acid derivatives. 

The discovery of this behavior was of great importance because a single product was converted into a variety of products. The conversion into primary amides or other carboxylic acid derivatives depended upon the structure of the Ugi adducts. An electron-rich N-acyl moiety was required for the formation of munch -nones, otherwise the primary amide was obtained [7]. The conversion of cydo-... 

Like other carboxylic acid derivatives, amides can be reduced by lithium aluminum hydride. The product of this reduction is an amine. 

The same mechanism is true for nucleophilic substitutions of other carboxylic acid derivatives with neutral nucleophiles (Following fig.). In practice, acids or bases are generally added to improve yields. 

When a nucleophile containing a heteroatom reacts at a carboxyl carbon SN, reactions occur that convert carboxylic acid derivatives into other carboxylic acid derivatives, or they convert carbonic acid derivatives into other carbonic acid derivatives. When an organometallic compound is used as the nucleophile, SN reactions at the carboxyl carbon make it possible to synthesize aldehydes (from derivatives of formic acid), ketones (from derivatives of higher carboxylic acids), or—starting from carbonic acid derivatives—carboxylic acid derivatives. Similarly, when using a hydride transfer agent as the nucleophile, SN reactions at a carboxyl carbon allow the conversion of carboxylic acid derivatives into aldehydes. 

All other carboxylic acid derivatives in Table 6.1, in which the leaving group is bound to the carboxyl carbon through an O atom, are increasingly better acylating agents than carboxylic acid alkyl esters (entry 3) in the order carboxylic acid phenyl ester (entry 4) < acyl isourea (entry 7) < mixed carboxylic acid/carbonic acid anhydride (entry 8) < carboxylic acid anhydride (entry 9) < mixed carboxylic acid anhydride (entry 10). 

Most other carboxylic acid derivatives can acylate only ketone enolates that are formed quantitatively. In these reactions, the acylation product is a /J-diketone, i.e., an active-methylene compound. As a consequence it is so acidic that it will be deprotonated quantitatively. This deprotonation will be effected by the ketone enolate. Therefore, a complete acylation of this type can be achieved only if two equivalents of the ketone enolate are reacted with one equivalent of the acylating agent. Of course, proceeding in that manner would mean an unacceptable waste in the case of a valuable ketone. 

The major use for acyl chlorides is as starting materials for the preparation of the other carboxylic acid derivatives. Acyl fluorides, bromides, and iodides could potentially be employed to prepare the other derivatives also. However, because they offer no advantages over the acyl chlorides, they are seldom used. 

By using the reactions described in Sections 19.2 through 19.6, it is possible to convert one carboxylic acid derivative to any other carboxylic acid derivative. Now let s examine the reactions of these compounds with hydride and organometallic nucleophiles. In these cases the products are no longer carboxylic acid derivatives. 

PC13 or PCI,) used to prepare other carboxylic acid derivatives. 

Amides Simple amides have much lower carbonyl stretching frequencies than the other carboxylic acid derivatives, absorbing around 1640 to 1680 cm-1 (often a close doublet). This low-frequency absorption agrees with the resonance picture of the amide. The C=0 bond of the amide carbonyl is somewhat less than a full double bond. Because it is not as strong as the C=0 bond in a simple ketone or carboxylic acid, the amide C=0 has a lower stretching frequency. 

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