Carboxy groups

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). 

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

Most xanthene dyes are classified as basic dyes by their method of appHcation acid dyes can be produced by introduction of sulfonic acid groups. The fluoresceins, which contain carboxy and hydroxy substituents, are also acid dyes for coloration of silk. Some of the fluoresceins in which the carboxy group has been esterified, are soluble in alcohol or other organic solvents and can be classified as solvent dyes. Mordant dyes can be produced by introducing o-dihydroxy or sahcyhc acid groups (2), which when metallised can have very good lightfastness. 

Polymer Solvent. Sulfolane is a solvent for a variety of polymers, including polyacrylonitrile (PAN), poly(vinyhdene cyanide), poly(vinyl chloride) (PVC), poly(vinyl fluoride), and polysulfones (124—129). Sulfolane solutions of PAN, poly(vinyhdene cyanide), and PVC have been patented for fiber-spinning processes, in which the relatively low solution viscosity, good thermal stabiUty, and comparatively low solvent toxicity of sulfolane are advantageous. Powdered perfluorocarbon copolymers bearing sulfo or carboxy groups have been prepared by precipitation from sulfolane solution with toluene at temperatures below 300°C. Particle sizes of 0.5—100 p.m result. 

Reactions. Although carbapenems are extremely sensitive to many reaction conditions, a wide variety of chemical modifications have been carried out. Many derivatives of the amino, hydroxy, and carboxy group of thienamycin (2) have been prepared primarily to study stmcture—activity relationships (24). The most interesting class of A/-derivatives are the amidines which are usually obtained in good yield by reaction of thienamycin with an imidate ester at pH 8.3. Introduction of this basic but less nucleophilic moiety maintains or improves the potency of the natural material while greatiy increasing the chemical stabiUty. Thus /V-formimidoyl thienamycin [64221-86-9] (MK 0787) (18), C 2H yN204S, (25) was chosen for clinical evaluation and... 

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

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. 

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-... 

Apparently a substantial spacer is also allowable between I he aromatic ring and the carboxy group. Gemfibrozi 1 (52), a iiypotriglyceridemic agent which decreases the influx of steroid into the liver, is a cl ofibrate homologue. It is made readily liy lithium di isopropyl amide-promoted alkylation of sodium iso-propionate with alkyl bromide 51. 

Because of resonance stabilization of the anion, a tet-nazolyl moiety is often employed successfully as a bioisosteric replacement for a carboxy group. An example in this subclass is provided by azosemide (27). Benzonitrile analogue is prepared by phosphorus oxychloride dehydration of the corresponding benzamide. Next, a nucleophilic aromatic displacement reaction of the fluorine atom leads to The synthesis concludes with the 1,3-dipolar addition of azide to the nitrile liinction to produce the diuretic azosemi de (27). ... 

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

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

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... 

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. 

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