Carboxylic acids solubility tests

Solubility in sodium carbonate solution. See Section 5 (p. 330), and also Test 2 for carboxylic acids (p. 347). 

Reactions between A -(l-chloroalkyl)pyridinium chlorides 33 and amino acids in organic solvents have a low synthetic value because of the low solubility of the amine partner. A special protocol has been designed and tested in order to circumvent this drawback. Soon after the preparation of the salt, an aqueous solution of the amino acid was introduced in the reaction medium and the two-phase system obtained was heated under reflux for several hours. However, this was not too successful because sulfur dioxide, evolved during the preparation of the salt, was converted into sulfite that acted as an 5-nucleophile. As a result, A -(l-sulfonatoalkyl)pyridinium betaines such as 53 were obtained (Section IV,B,3) (97BSB383). To avoid the formation of such betaines, the salts 33 were isolated and reacted with an aqueous solution of L-cysteine (80) to afford thiazolidine-4-carboxylic acids hydrochlorides 81 (60-80% yields). 

A preliminary test for the biodegradability of the 3-phenyl- and 3-carbamoyl-2(lH)pyridones was conducted in a barnyard humus suspension. The analysis by HPLC showed some loss, and the fluorescent compounds seemed to be adsorbed onto the solid. The 3-carbamoyl-2(lH)pyridone (II) also hydrolyzed to 3-carboxylic acid-2(lH)pyridone both in the slurry test and in water solutions that had been left standing 1-2 weeks. In preliminary tests both the 3-phenyl- and the 3-carbamoyl-2(lH)pyridones apparently adsorbed to some extent on silica sand columns. In addition, the solubility of both 1-H compounds was somewhat low, 1.3 x 10 M for II, and 1.0 x 10 M for IV. 

Hydrogenation of the carbonyl function is an important synthetic transformation and can be catalyzed by complexes of several transition metals including -among others- Co, Rh, Ru, Ir, and Os. In aqueous organometallic catalysis the first examples were given by the hydrogenation of water-soluble 2-oxo-carboxylic acids, 1,3-dihydroxyacetone and fmctose [47-54], later the same substrates were also used for testing new catalysts [29]. 

Solubility in 5 per cent sodium hydrogen carbonate solution. If the compound is soluble in 5 per cent sodium hydroxide solution, test its solubility in a 5 per cent solution of sodium hydrogen carbonate. Observe whether it dissolves and particularly whether carbon dioxide is evolved either immediately (carboxylic acids, sulphonic acids, negatively substituted phenols) or after a short time (some amino acids). 

These acid-base reactions allow a simple way distinguishing between most carboxylic acids, phenols, and alcohols. Since the salts formed from the acid-base reaction are water soluble, compounds containing these functional groups can be distinguished by testing their solubilities in sodium hydrogen carbonate and sodium hydroxide solutions. This solubility test is not valid for low molecular weight structures like methanol or ethanol since these are water soluble and dissolve in basic solution because of their water solubility rather than their ability to form salts. 

Methylation of hydrolyzed or methanolized copolymers. One gram samples of hydrolyzed or methanolized copolymers were suspended or dissolved in dry benzene and the mixtures were treated with diazomethane until methylation was complete. This was indicated by the complete dissolution of the copolymers and by the presence of the yellow color of diazomethane in the reaction mixtures for 8 hrs. The reaction mixtures were poured into methanol to precipitate the products, which were reprecipitated twice from benzene solution into methanol before being dried in vacuo. Completely methylated copolymers were soluble in CCli, but copolymers containing very small amounts of acid units were not. This simple test was employed routinely to ensure the completeness of methylation. The 1H-NMR spectra of the copolymers in C D6 solution were examined for the presence of carboxylic acid proton resonances at 5=11.5 ppm as an additional criterion for the completeness of methylation. 

The test identifies the substance to be examined as either a benzoate salt or a substance that yields benzoic acid upon chemical manipulation. Reference to benzoates is at present made in only three monographs describing benzoic acid (Figure 3.11.1) itself, ifs sodium salt, and benzoyl peroxide, which upon basic hydrolysis yields two benzoic acid equivalents. Being a carboxylic acid, benzoic acid has a water solubility that depends strongly on the pH of the solution. The free acid is sparingly soluble in cold water but significantly more soluble in hot water. It is soluble in alcohol and ether. All common benzoate salts except the salts of silver and basic iron(III) are water soluble. 

The test identifies the substance to be examined as a salt of potassium, K+. As with other alkali metals, potassium is exclusively found as the monovalent cation. Since almost all salts of potassium are water soluble and it is a very inert ion, as a rule these do not contribute to the characteristics of its salt. For this reason its function in the compounds enrolled in the pharmacopoeia is to be an indifferent counter-ion, both for simple inorganic anions but also for anionic active pharmaceutical ingredients. Reference to potassium is made in about twenty-five monographs. In about half of them test (b) is dictated in about one-quarter and in the last quarter both tests have to be performed. The anions in the organic salts are, with the exception of Acesulfame, carboxylic acids. Due to the high water solubility of potassium, sample preparation is in most cases just a simple dilution in water. 

The test ensures that the substance to be examined has a total content of calcium (Ca ), which is below the limit defined in the individual monograph. The calcium is like the rest of the alkaline-earth metals — a divalent cation. It forms soluble halogen and nitrate salts, whereas the carbonate, sulfate, phosphate, and oxalate are insoluble. Calcium is not toxic but on the contrary an essential mineral in the human diet. So, the main reason for limiting its presence in substances used in pharmaceuticals is that it could be used as a marker for insufficient reagent cleanup during synthesis of the substance. Some carboxylic acid, like lactic acid, is first precipitated as calcium salts upon which purification steps are then performed. After this the carboxylic acid can be reprecipitated as whatever salt needed. At the present reference to calcium is given in more than 100 monographs. 

---