Acid-base salts

While basic drugs are protonated with a broad range of different acids, the bases used to deprotonate acidic drugs have far less variety. Carboxylic acids, with a pKa in the 4 to 5 range, are almost always converted into sodium salts. Potassium and calcium are also occasionally encountered. Carboxylate salts do not have any general chemical stability advantages as found with protonated amines. 

The following Case Study demonstrates some of the advantages that can be gained by converting a neutral drug into a salt. 

RPR 200,735 is a weak base. Its conjugate acid has a pA a of 5.3. Only strong acids are able to form a stable salt with RPR 200,735. Investigated acids include hydrochloric acid, hydrobromic acid, and methanesulfonic acid (Table 13.2). The methanesulfonate salt was found to be superior to the other salts in all aspects water solubility, hygroscopy (absorption of moisture from air), and rate of dissolving. Furthermore, the flow properties of the methanesulfonate salt facilitated capsule and tablet preparation. 

Test Methanesulfonate Salt Chloride Salt Bromide Salt 

Hygroscopy Nonhygroscopic stable, monohydrate Hygroscopic, multiple hydrated forms Hygroscopic, multiple hydrated forms 

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The chemistry of amines ts dominated by the lone pair of electrons on nitrogen, which makes amines both basic and nucleophilic. They react with acids to form acid-base salts, and they react with electrophiles in many of the polar reactions seen in past chapters. Note in the following electrostatic potential map of trimethylamine how the negative (red) region corresponds to the lone-pair of electrons on nitrogen. 

More recently considered candidates are large molecular anions with delocalized anionic charge, which offer low lattice energies, relatively small ion-ion interaction, and hence sufficient solubility and relatively large conductivity. Delocalization of the charge is achieved by electron-with drawing substituents such as -F or - CF3. Furthermore, these anions show a good electrochemical stability to oxidation. In contrast to Lewis acid-based salts they are chemically more stable with various solvents and often also show excellent thermal stability. 

Alkaline chemical, opposite of acid, as in the equation Acid + Base - Salt + Water. 

Inorganic solvents (acids, bases, salt solutions, mixtures of acids bases, and their salts). 

VIII. Acid + Base — Salt + Water (Neutralization)... 

During manufacture, many reagents are exposed to metal. It is recommended that the highest-purity acids, bases, salts, ligands, chelates, and other reagents be used. It is best if none of the extracting solutions contain the analyte of interest. If this is not possible, then care must be taken to make sure that the appropriate blanks are used during analysis. 

Examples are residual organic amines, organic and inorganic acidic and basic impurities (acids, bases, salts ), and detergents. ... 

Acid + Base Salt + Water but it was soon noticed that the treatment was not perfect because it required a balance of one to one molecule of the reagents and the exothermic character of the reaction was ignored. 

Mass intensity measures the amount of material needed to synthesize the desired product. It takes into account yield, reaction stoichiometry, solvents, and reagents in a reaction mixture, and this covers everything that is put into a reaction vessel. It also includes all mass used in acid, base, salt and organic solvent washes, and organic solvents used in extractions, crystallizahons, or solvent switching. 

Scheme 5.15 Acid-base-salt turning cycle in the one-pot process.

Stage II Selection of acid/base/salt form (3-25)... 

ELECTROLYTE IMBALANCE Improper proportions of acids, bases, salts, and fluids in the body. Electrolytes include the salts sodium, potassium, magnesium, chloride chlorine. They can conduct electricity, and therefore are essential in nerve, muscle, and heart function. 

Acid-Base Salts Principles of Green Chemistry... 

Then the reactivity of the tetracarboxylic acid-based salt monomers was compared with that of the salts consisting of tetracarboxylic acid half diesters. The P-XPM series polyimides were prepared by the high-pressure polycondensation of salt monomers XPME derived from the aliphatic diamines and pyromellitic acid half diethyl ester (see Eq. 5, Ar=PM and R=ethyl) [20], in addition to the polymers obtained from the pyromellitic acid-based salt monomer XPMA [24] already shown in Table 1. The polycondensation of salts XPME proceeded readily under high pressure of 250 MPa at 240 °C for 15 h, even with the elimination of ethanol and water as the by-products in the closed reaction vessel, and this afforded the polyimides with inherent viscosities up to 1.6 dL/g. Therefore, the reactivity of salt monomers XPME was found to be almost comparable to that of the parent salt XPMA, and the properties of the resultant P-XPM series polyimides from XPME were the same as those obtained from salts XPMA. 

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