Carboxylic acids, conversion exchange with acid

Conversion of the carboxylic acid to the diethyl amide interestingly leads to an agent that exhibits the properties of a respiratory stimulant. One synthesis of this agent starts with the preparation of the mixed anhydride of nicotinic and benzene-sulfonic acid (4). An exchange reaction between the anhydride and diethyl benzenesulfonamide affords nikethemide (5). ... 

One of the earliest attempts to prepare analogues of FA as potential inhibitors involved the synthesis of 2-amino-4,7-dihydroxypteridine-6-carboxylyl-p-ami-nobenzoic acid (612) (in which the change from the structure of FA itself is exchange of the methylene bridge for a carbonyl group, and oxidation of position 7 to a lactam). This compound, which was a surprisingly effective inhibitor, was prepared from isoxanthopterin carboxylic acid (611) by in situ conversion to its acid chloride with a mixture of phosphorus oxychloride and phosphorus pentachloride, followed by addition of p-aminobenzoylglutamic acid (Scheme 3.132) [115]. 

Dess-Martin A5-iodane 44 is an extremely useful reagent for the conversion of primary and secondary alcohols to aldehydes and ketones at 25 °C [70]. It does not oxidize aldehydes to carboxylic acids under these conditions. It selectively oxidizes alcohols in the presence of furans, sulfides, and vinyl ethers. The oxidation mechanism involves a facile ligand exchange with alcohols, followed by reductive /1-elimination. 

An acyl bromide can readily exist in the end form, and this tautomer is rapidly brominated at the a-carbon. The monobrominated compound is much less nucleophilic, so the reaction stops at this stage. This acyl intermediate compound can undergo bromide exchange with unreacted carboxylic acid via the anhydride, which allows the catalytic cycle to continue until the conversion is complete. 

Lundquist et al. (76) reported a method for the analysis of the metabolite 2-aminothiazoline-4-carboxylic acid (18) in urine using LC with fluorescence detection after conversion to N-carbamylcysteine by heating with alkali. The analyte was concentrated from urine by cation exchange resin and further processed to remove interfering thiols and disulfides. The LOD was rather high at 0.3 xM. 

Diaryl Tellurium Dicarboxylates4 5g of Amberlite IR45 resin in the OHe-form (theoretical exchange capacity 2 mequiv/ml) are placed in a 10 mm ID glass tube. A 4% ethanolic solution of the carboxylic acid in ethanol is slowly passed through the resin until the conversion to the carboxylate form is complete. The resin is washed with ethanol to remove excess carboxylic acid and dried in a stream of nitrogen. 1 mmol of the diaryl tellurium dichloride is dissolved in 20 ml of THF/ethanol (1/1, v/v) and this solution is slowly passed through the resin. The resin is rinsed with 50 ml of the solvent mixture, the combined effluents are evaporated in a rotary evaporator, and the crude dicarboxylates, obtained in 100% yield, arc recrystallized from benzene/petroleum ether. 

With simple carboxylic acids and amines, direct conversion to amides takes place at elevated temperatures (equation 1). Generally, this reaction may be catalyzed by acid ° or by cation exchange resin. Addition of ammonium carbonate or urea as a source of ammonia reduces reaction temperatures and improves yields. 

The conversion of carboxyl groups into trifluoromethyl groups proceeds in two steps. The first step, exchange of the hydroxy group by fluorine, can be accomplished easily by use of less potent fluorination agents such as a-fluoroenamines or DAST. Subsequent conversion of the carboxylic acid fluoride into the trifluoromethyl group requires more drastic conditions and can be achieved only with SF4. The most convenient procedure is the one-step direct reaction of carboxylic acids with SF4 in aHF as solvent (Scheme 2.66). For most aliphatic and aromatic carboxylic acids, excellent yields can be obtained even at room temperature or below. 

Cyanide can be regenerated from methaemo-globin by treatment with acid. There are many methods for detecting free and bound cyanide, and thiocyanate in blood these have recently been reviewed (Black and Muir, 2003 Black and Noort, 2005). They have been applied mostly to the determination of cyanide levels in smokers and fire victims rather than cases of deliberate poisoning. 2-Aminothiazoline-4-carboxylic acid has been analysed in urine using LC with fluorescence detection after conversion to N -carbamylcysteine (Lundquist et al, 1995), and by GC-MS after conversion to its tris-trimethylsilyl derivative (Logue etal., 2005). The analyte was concentrated from urine on a cation exchange resin. 

Ion exchange papers. A combination of the specificity of ion exchange with the convenience of paper chromatography is afforded by ion exchange papers. There are two kinds. One consists of cellulose where acidic groups have been introduced by chemical modification of the -OH groups, e.g. conversion to carboxylic, phosphoric and sulphonic acids and to A,A-dialkylamines. These papers are suitable for the separation of cations, amines and amino acids. 

Characterization. Polymer composition was determined by a variety of classical analytical techniques that included elemental analysis and NMR. The carboxyl content of the polymers was determined by potentiometric titration following conversion to the acid form with an ion-exchange column. Analysis of the sodium content in the polymers gave carboxyl values within a few percent of those found by the titration technique. The number of hydrophobic groups in the polymers in this study was too low to allow quantification by conventional analytical techniques. The levels cited in this chapter refer to amounts added to the reactor and complete incorporation into the polymer was assumed. A recent study (8) using a UV spectroscopic technique on model hydrophobic monomers indicated that this was a fairly good assumption. 

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