Carboxy group, electronic effects

COOR Penicillins Esterification of the C(3) carboxy group Electron-withdrawing effect makes /3-lactam carbonyl C-atom more electrophilic, and intramolecular acylamido participation (see Fig. 5.9) Increased ca. 16-fold [91]... 

The effect of a carboxy group is illustrated by the reactivity of 2-bromopyridine-3- and 6-carboxylic acids (resonance and inductive activation, respectively) (cf. 166) to aqueous acid under conditions which do not give hydroxy-debromination of 2-bromopyridine and also by the hydroxy-dechlorination of 3-chloropyridine-4-car-boxylic acid. The intervention of intermolecular bifunctional autocatalysis by the carboxy group (cf. 237) is quite possible. In the amino-dechlorination (80°, 4 hr, petroleum ether) of 5-carbethoxy-4-chloropyrimidine there is opportunity for built-in solvation (167) in addition to electronic activation. This effect of the carboxylate ion, ester, and acid and its variation with charge on the nucleophile are discussed in Sections I,D,2,a, I,D,2,b, and II,B, 1. A 5-amidino group activates 2-methylsulfonylpyridine toward methanolic am-... 

HMO calculations have been ultilized in the search for substituted thiepins liable to be good candidates for synthesis due to electronic substituent effects.7 Based on these results, the presence of at least two carboxy groups and one fluorine group give an increased resonance energy per electron to positive values, indicating at least some thermal stability. 

The presence of the electron-withdrawing trifluoromethyl substituent in the a-position has a dramatic effect on the reactivity of both the carboxy and the amino groups. The latter, in particular, shows a very marked decrease ( 4 units) in the pK.t value with respect to the corresponding natural amino acids, whereas the carboxy group experiences a more limited deviation (0.3-1.1 units) 111 As a consequence, activation of the carboxy group of... 

A carboxy group is a rather weak electron-withdrawing substitutent and its electronic effect on the adjacent double bond is negligible. The fact that the straightforward synthesis of cyclo-propanecarboxylic acids via the addition of dichlorocarbene to alk-2-enoic acids has met with a little success is, therefore, due to the acidic properties of this substituent. 

Section 19.4 Carboxylic acids are weak acids and, in the absence of electron-attracting substiments, have dissociation constants of approximately 10 (pA a = 5). Carboxylic acids are much stronger acids than alcohols because of the electron-withdrawing power of the carbonyl group (inductive effect) and its ability to delocalize negative charge in the carboxy-late anion (resonance effect). 

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. 

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