Carboxy groups

A 2-carboxy group can be easily replaced by a hydrogen upon heating (11, 12, 14-16). 

With a carboxy group on the alkyl chain of the alkylthio substituent. C-4 may be involved in an intramolecular nucleophilic substitution to give 159 (Scheme 84). 

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- 

From this, the A -methyl and carboxy groups are in as positions whereas the carboxy and methoxy groups are trans and so tra s -A -methy]-4-methoxyproline, G, is the structure implied. The NMR measurements do not provide an answer as to which enantiomer it is, 2R,4S as shown or the mirror image 2S,4R. 

Saponification next frees the carboxy group for condensation with -butyl 7-aminocephalosporinate mediated by dicyclohexyl-carbodiimide and 1-hydroxybenzotriazole. The synthesis is 

Reference to the deshielding of a ring proton by an ortho carboxy group clarifies the assignment. 

Sarpicillin (10) is a double prodrug of ampicillin in that not only is the carboxy group masked as an ester, but a 

The attractive properties of cromolyn as an inhibitor of the release of mediators of anaphylaxis has inspired many attempts to improve on the antiasthmatic characteristics of that substance. One such agent is cromitrile (6). In this case, a tetrazolyl unit is introduced as a carboxy group 

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