Functional group equivalents carboxylic acids

The polyprotic acid, para-hydroxybenzoic acid, has two functional groups, a carboxylic acid and a phenolic group. Each group has an ionizable proton. Given just two basic pieces of titration data, we used concepts from this and the preceding chapter to determine the pK values for both ionizable groups as well as the pH at the two equivalence points. As a check, note that the pK values of these groups are comparable to the values for their parent compounds, acetic add and... 

Many other examples of synthetic equivalent groups have been developed. For example, in Chapter 6 we discussed the use of diene and dienophiles with masked functionality in the Diels-Alder reaction. It should be recognized that there is no absolute difference between what is termed a reagent and a synthetic equivalent group. For example, we think of potassium cyanide as a reagent, but the cyanide ion is a nucleophilic equivalent of a carboxy group. This reactivity is evident in the classical preparation of carboxylic acids from alkyl halides via nitrile intermediates. 

Examples of this approach to the synthesis of ketones and carboxylic acids are presented in Scheme 1.6. In these procedures, an ester group is removed by hydrolysis and decarboxylation after the alkylation step. The malonate and acetoacetate carbanions are the synthetic equivalents of the simpler carbanions lacking the ester substituents. In the preparation of 2-heptanone (entries 1, Schemes 1.5 and 1.6), for example, ethyl acetoacetate functions as the synthetic equivalent of acetone. It is also possible to use the dilithium derivative of acetoacetic acid as the synthetic equivalent of acetone enolate.29 In this case, the hydrolysis step is unnecessary, and decarboxylation can be done directly on the alkylation product. 

The reactions catalyzed by Lewis acids are conducted for 10-20 hours at — 20 C to give hypochlorites in almost quantitative yield.82 Chlorine monofluoride activated by hydrogen fluoride to enhance its electrophilicity transforms the carbonyl function in esters of carboxylic acids to a difluoromethyl group. The reactions are carried out by passing 2molar equivalents of chlorine monofluoride gas through a solution of the ester in an equal volume of hydrogen fluoride at - 70 to - 30°C.83... 

The oxazoles and their derivatives have played a variety of fascinating roles in the preparation of new molecular systems. Much of this chemistry stems from their ability to serve as diene components (azabutadiene equivalents) in reactions with a variety of dienophilic agents, to undergo nuclear metallation, to activate attached aryl or alkyl groups to deprotonation (thus functioning as masked aldehydes, ketones or carboxylic acid groups), and to serve as useful electrophiles on conversion to AT-alkylated salts. 

DCCI, the modified polymers were found to contain considerable amounts of N-acy-lureic groups originating from side reactions between DCCI and the y-carboxylic acid functions. The formation of N-acylureic groups was completely suppressed when the modification reactions were carried out in the presence of one equivalent of hydroxy-benzotriazole.[21,22]... 

Primary alcohols afforded the corresponding carboxylic acids via further oxidation of the aldehyde intermediate, e.g. 1-hexanol afforded 1-hexanoic acid in 95% yield. It is important to note, however, that this was achieved without the requirement of one equivalent of base to neutralize the carboxylic acid product (which is the case with supported noble metal catalysts). In contrast, when 1 mol% TEMPO (4 equivalents per Pd) was added, the aldehyde was obtained in high yield, e.g. 1-hexanol afforded 1-hexanal in 97% yield. Under cosolvent conditions using water/ethylene carbonate, Pd-neocuproine was found to be even more active (Fig. 4.65) [174]. This system is exceptional because of its activity (TOF 500h-1 could be reached for 2-octanol) and functional group tolerance, such as C=C bonds, C = C bonds, halides, a-carbonyls, ethers, amines etc. Thereby this system is expected to have a broad synthetic utility. 

Pivaloyloxymethyl (Pom) esters are useful as prodrugs of penicillin and other 0-lactam antibiotics owing to their easy hydrolysis in vivo by ubiquitous non-specific esterases. Mascaretti and co-workers showed that Pom esters can also by cleaved under mild conditions with 2 equivalents of bis(tri-/i-butyltin)oxide as shown in Scheme 6.32. The intermediate tributylstannyl esters are readily hydrolysed on treatment with water to release the carboxylic acid. Functional groups such as aldehydes, thioacetals, amides, vinyl bromides, and nitro compounds are compatible.22... 

There are several other reactions pertinent to functional groups present in pyridazine iV -oxides. The cyano group of 6-cyano-3-methylpyridazine 1-oxide is normally hydrolyzed to the carboxyl in concentrated sulfuric acid, whereas heating 5-chloro-6-cyano-3-methylpyridazine 1-oxide with 2 equivalents of sodium methoxide in a sealed tube gave 6-carbamoyl-5-hydroxy-3-methylpyridazine... 

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