Reaction of carboxylation

The most general synthetic route to ketones uses the reaction of carboxylic acids (or their derivatives) or nitriles with organometallic compounds (M.J. Jorgenson, 1970). Lithium car-boxylates react with organolithium compounds to give stable gem-diolates, which are decom-... 

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... 

Summary of Reactions of Carboxylic Acids Discussed in Earlier Chapters... 

Section 19 13 Among the reactions of carboxylic acids their conversions to acyl chlo rides primary alcohols and esters were introduced m earlier chapters and were reviewed m Table 19 5... 

Reaction of carboxylate ion with nitrophenyl sulfites gives the carboxylate -nitrophenyl esters. If the -nitrophenyl sulfite is unsymmethcal (02NCgH40S(0)0R, where R is ethyl or phenyl), carboxylate attacks the -nitrophenyl side (69). Some amino acids react with methyl and benzyl sulfites in the presence of -toluenesulfonic acid to give methyl and benzyl esters of the amino acids as -toluenesulfonate salts (70). With alcohols, the conversion of henzil to a monoacetal upon addition of sulfuric acid to the henzil in methanol and dimethyl sulfite proceeds in high yield (71). 

Fig. 8. Crosslinking reactions of carboxylated waterborne polyurethane dispersions.

The haloalkane dehydrogenase is believed to act by using one of its side-chain carboxylates to displace chloride by an Sn2 mechanism. (Recall the reaction of carboxylate ions with alkyl halides from Table 8.1.)... 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

In the following the reaction is outlined for an a-bromination. The reaction mechanism involves formation of the corresponding acyl bromide 3 by reaction of carboxylic acid 1 with phosphorus tribromide PBr3. The acyl bromide 3 is in equilibrium with the enol derivative 4, which further reacts with bromine to give the a -bromoacyl bromide 5 ... 

Reaction of carboxylic acids, aldehydes or ketones with hydrazoic acid... 

The reaction of carboxylic acids, aldehydes or ketones with hydrazoic acid in the presence of a strong acid is known as the Schmidt reaction A common application is the conversion of a carboxylic acid 1 into an amine 2 with concomitant chain degradation by one carbon atom. The reaction of hydrazoic acid with a ketone 3 does not lead to chain degradation, but rather to formation of an amide 4 by formal insertion of an NH-group. 

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

Figure 20.2 Some general reactions of carboxylic acids.

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. 

Perhaps the most useful reaction of carboxylic acids is their conversion into esters. There are many methods for accomplishing the transformation, including the S -2 reaction of a carboxylate anion with a primary alkyl halide that we saw in Section 11.3. 

The most common reactions of carboxylic acid derivatives are substitution by water (hydrolysis) to yield an acid, by an alcohol (alcoholysis) to yield an ester, by an amine (aminolysis) to yield an amide, by hydride ion to yield an alcohol (reduction), and by an organometallic reagent to yield an alcohol (Grignard reaction). 

Reactions of carboxylic acids (Section 21.3) (a) Conversion into acid chlorides... 

One frequently used method for preparing methyl esters is by reaction of carboxylic acids with diazomethane, CH2N2. 

Decarboxylation is not a general reaction of carboxylic acids. Rather, it is unique to compounds that have a second carbonyl group two atoms away from the —COoH. That is, only substituted malonic acids and /3-keto acids undergo loss of CC>2 on heating. The decarboxylation reaction occurs by a cyclic mechanism and involves initial formation of an enol, thereby accounting for the need to have a second carbonyl group appropriately positioned. 

Studying the reaction of carboxylic oligoesters with monohydric alcohols, Sorokina and Barshtein2231 found the reaction orders 1 and 0.5 with respect to acid and alcohol. However, they did not determine the reaction order relative to catalyst. According to these authors, the most important steps are ... 

This chapter covers not only nuclear and extranuclear quinoxahnecarboxylic acids (and anhydrides) but also the carboxylic esters, acyl halides, carboxamides, carbohydrazides, carbonitriles, carbaldehydes, and (ketonic) acyl derivatives of quinoxaline a few related speceis are also included. To avoid repetition, the interconversions of these quinoxaline derivatives are discussed only at the first opportunity thus the esterification of quinoxalinecarboxylic acids in covered 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, appropriate cross-references have been inserted. 

The above results pertain to reactions in solution. In the gas phase reactions can take a different course, as illustrated by the reaction of carboxylic esters with MeO, which in the gas phase was shown to take place only by the Bal2 mech-anism, ° even with aryl esters, ° where this means that an Sn2 mechanism takes place at an aryl substrate. However, when the gas-phase reaction of aryl esters was carried out with MeO ions, each of which was solvated with a single molecule of MeOH or H2O, the Bac2 mechanism was observed. 

For a review of Sn2 reactions of carboxylic esters, where the leaving group is OCOR, see McMurry, J.E. Org. React., 1976, 24, 187. 

---