Carboxylates substitution reactions

In addition to providing fully alkyl/aryl-substituted polyphosphasenes, the versatility of the process in Figure 2 has allowed the preparation of various functionalized polymers and copolymers. Thus the monomer (10) can be derivatized via deprotonation—substitution, when a P-methyl (or P—CH2—) group is present, to provide new phosphoranimines some of which, in turn, serve as precursors to new polymers (64). In the same vein, polymers containing a P—CH group, for example, poly(methylphenylphosphazene), can also be derivatized by deprotonation—substitution reactions without chain scission. This has produced a number of functionalized polymers (64,71—73), including water-soluble carboxylate salts (11), as well as graft copolymers with styrene (74) and with dimethylsiloxane (12) (75). 

During certain substitution reactions, the carboxyl group is often replaced by the entering group. An example is fuming nitric acid, which results in the formation of trinitrophenol. Another is the bromination of saUcyhc acid in aqueous solution to yield 2,4,6-tribromophenol [25376-38-9] (eq. 6). 

Amides are the least reactive carboxylic acid derivative, and the only nucleophilic acyl substitution reaction they undergo is hydrolysis. Amides are fairly stable in water, but the amide bond is cleaved on heating in the presence of strong acids or bases. Nominally, this cleavage produces an amine and a car boxylic acid. 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

The reaction of wasabi phytoalexin (109) with excess 15% aqueous NaSMe gives methyl 2-methylthioindole-3-carboxylate (184,70%) and 140 (20%). In this reaction, formation of 2-methylthioindole-3-carboxylic acid (185) is not observed under various reaction conditions. The fact indicates that once 140 is formed, it does not undergo nucleophilic substitution reaction. In addition, hydrolysis of the... 

Nucleophilic Acyl Substitution Reactions of Carboxylic Acid Derivatives (Chapter21)... 

As a general rule, nucleophilic addition reactions are characteristic only of aldehydes and ketones, not of carboxylic acid derivatives. The reason for the difference is structural. As discussed previously in A Preview of Carbonyl Compounds and shown in Figure 19.14, the tetrahedral intermediate produced by addition of a nucleophile to a carboxylic acid derivative can eliminate a leaving group, leading to a net nucleophilic acyl substitution reaction. The tetrahedral intermediate... 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

Carboxylic Acid Derivatives Nucleophilic Acyl Substitution Reactions... 

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. 

Carboxylic acid derivatives are among the most widespread of all molecules, both in laboratory chemistry and in biological pathways. Thus, a study of them and their primary reaction—nucleophilic acyl substitution—is fundamental to understanding organic chemistry. We ll begin this chapter by first learning about carboxylic acid derivatives, and then we ll explore the chemistry of acyl substitution reactions. 

The addition of a nucleophile to a polar C=0 bond is the key step in thre< of the four major carbonyl-group reactions. We saw in Chapter 19 that when. nucleophile adds to an aldehyde or ketone, the initially formed tetrahedra intermediate either can be protonated to yield an alcohol or can eliminate th< carbonyl oxygen, leading to a new C=Nu bond. When a nucleophile adds to carboxylic acid derivative, however, a different reaction course is followed. Tin initially formed tetrahedral intermediate eliminates one of the two substituent originally bonded to the carbonyl carbon, leading to a net nucleophilic acy substitution reaction (Figure 21.1. ... 

A nucleophilic acyl substitution reaction involves the substitution of a nucleophile for a leaving group in a carboxylic acid derivative. Identify the leaving group (Cl- in the case of an acid chloride) and the nucleophile (an alcohol in this case), and replace one by the other. The product is isopropyl benzoate. 

Esters can also be synthesized by an acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol, a process called the Fischer esterification reaction. Unfortunately, the need to use an excess of a liquid alcohol as solvent effectively limits the method to the synthesis of methyl, ethyl, propyl, and butyl esters. 

We said in Section 17.4 that carboxylic acids are reduced by L1AIH4 to give primary alcohols, but we deferred a discussion of the reaction mechanism at that time. In fact, the reduction is a nucleophilic acyl substitution reaction in which —H replaces -OH to give an aldehyde, which is further reduced to a primary alcohol by nucleophilic addition. The aldehyde intermediate is much more reactive than the starting acid, so it reacts immediately and is not isolated. 

Conversion of Acid Halides into Anhydrides Nucleophilic acyl substitution reaction of an acid chloride with a carboxylate anion gives an acid anhydride. Both symmetrical and unsymmetrical acid anhydrides can be prepared in this way. 

The chemistry of carboxylic acid derivatives is dominated by the nucleophilic acyl substitution reaction. Mechanistically, these substitutions take place by... 

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