Normal Carboxylic Acids

In concentrated solution 7-methylisatin-4-carboxvlic acid exhibits normal carboxylic acid dimerization, but in the solid state the lactol form 58 is present.228 Infrared studies indicate that hydrogen bonding as shown in 59 best represents the structure and mode of association of... 

In the second step, a nucleophile (such as Br or a water molecule) attacks an electron-deficient carbon of the hybrid 16. Attack at the carboxyl carbon may occur but does not lead to a stable product. Attack of the nucleophile at the /3 carbon, however, produces the enol form of the -substituted acid, which then is converted rapidly to the normal carboxylic acid ... 

GC Retention time indices (Ig) The Ig values were calculated by linear interpolation of the unknown between retention times of a series of methyl esters of normal carboxylic acids under the GC conditions cited for OV-17 column and nitrogen as carrier gas. The method was similar to the one suggested by Van den Dool and Kratz (4j. The I value of each standard was arbitrarily given the carbon number of the acid of the ester thus hexanoate was given a value of 6.0. The IF values of the various peaks in the total extracts (SDE method) of all the three samples and of various authentic compounds were determined under corresponding GC conditions using the same column. 

Fig. 7.5. Application of the reaction principle underlying Figure 7.4 for the conversion of tertiary carboxylic acid amides into acylating agents for alcohols. Very mild workup conditions lead to the orthoesters D, while the normal carboxylic acid esters B are obtained with aqueous standard workup.

This latter thought has an important consequence if compounds with C=0 double bonds are sorted in decreasing order of resonance stabilization of their C=0 group they are at the same time sorted according to their increasing propensity to enolization. So as the resonance stabilization of the C=0 double bond decreases from 22 kcal/mol to somewhere near zero in the order carboxylic acid amide > carboxylic acid ester/carboxylic acid > ketone > aldehyde > carboxylic acid chloride/-bromide, the enol content increases in this same order (Figure 12.2). These circumstances immediately explain why no enol reactions whatsoever are known of carboxylic acid amides, virtually none of normal carboxylic acid esters/carboxylic acids, but are commonly encountered with ketones, aldehydes and carboxylic acid halides. 

Fig. 13.51. a-Methylenation of a lactone via Mannich reaction (cf. Figure 12.14 and 12.15) of the a-carboxylated lactone enolate or lactone enol derived thereof. Another approach to a-methylenation of not only lactones, but normal carboxylic acid esters, is presented in Figure 13.50. 

Many carboxy derivatives are available by primary syntheses. Otherwise the best route to simple pyrimidinecarboxylic acid derivatives is oxidative. This statement is even more applicable to our present situation with readily available acyl-, alkenyl-, or alkynylpyrimidine substrates from the coupling procedures, which serve as excellent substrates for oxidative reactions. The normal carboxylic acid reactions are observed ester formation, ester hydrolysis, aminolysis, acid chloride formation and reactions. A carboxy group in an electrophilic position may readily be lost when the pyrimidine ring is further depleted of 7t-electrons by its substitution pattern selective decarboxylation can be effected in pyrimidinedicarboxylic acids. 

It is apparent that the Lewis-acid solvents (alcohols, carboxylic acids, and chlorinated hydrocarbons) provide much better selectivity for a given capacity than do the Lewis-base solvents (ketones, esters, amines, phosphoryls). Furthermore, branching of the solvent molecule is important, as shown In Fig. 15.2-7. The dashed lines relate selectivity so KD for normal carboxylic acids (solid points) and normal alcohols (open points). Branched carboxylic acids give substantially higher selectivities than do straight-chain acids for a given value of K0. The same is liue for alcohols. 

Orthoesters can be regarded as ketals of carboxylic esters and can be hydrolysed analogously to ketals. This fission has no preparative value since it leads to the normal carboxylic acids which can, without exception, be prepared more conveniently in other ways. 

As mentioned above (page 1018), thermal decarbonylation of non-enolizable a>oxo carboxylic acids is preferably carried out with their anils, but it can also be effected by concentrated sulfuric acid. For example, phenylglyoxylic acid is cleaved to benzoic acid and carbon monoxide when gently warmed in concentrated sulfuric acid. Such decarbonylations catalysed by protonic acids are known also for normal carboxylic acids such as triphenylacetic59 and... 

These observations suggested a cyclic intermediate (I) in which parts of the two reacting molecules supply the bulk of the stabilisation for the charged intermediates. The normal carboxylic acid formed in the oxidation was not... 

The three p/C.,s for citric acid are 3.1,4.7, and 5.4. Explain why the first pK is lower than for normal carboxylic acids, and why the third pK, is higher than normal. 

And then there are the normal carboxylic acids, both straight chain and branched chain, which are found in sweat... 

The Ka value is about 10 . By applying this relation and from thepK values of normal protonated aliphatic amines (8.5-10.5) and of normal carboxylic acids (3.6-5.0), it is clear that the microscopic constant 12 imposes its value quasi-exclusively to the macroscopic constant Ka. It is clear also that if the amine function disappears after a chemical reaction, the only acid that remains is the carboxylic function. The macroscopic constant Ka value must tend then to that of the microscopic constant k22 and its titration by a sodium hydroxide solution must become possible. 

In one of the components of the mixture, the acidity is brought by a carboxylic rest, while in the other, it is one of the protonated amines that is acidic. This mixture is globally represented by the symbol H2Y . The composition of this mixture is constant regardless of the pH value (see the problem with the microconstants— Chap. 5). Moreover, pKa = 1.99 and even pKai =2.67 are values that are too low to belong to normal carboxylic acids, but this point cannot be explained by the occurrence of several protonation sites. They probably should be ascribed to structural factors, such as, for example, the withdrawing inductive effect of the protonated amino group located at the proximity of the carboxylic groups of interest. pK 4 = 10.26 seems to be a normal value for a protonated amine. The structure of the HY form should probably be written as... 

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