Aqueous dilution solubility method

Saponification of esters. Aqueous sodium hydroxide method. To hydrolyse an ester of an alcohol, reflux 5-6 g. with 50 ml. of 20 per cent, sodium hydroxide solution for 1-2 hours or until the ester layer disappears. Distil the alkahne mixture and collect about 6 ml. of distillate. This will contain any volatile alcohol formed in the saponification. If the alcohol does not separate, i.e., is water-soluble, saturate the distillate with sohd potassium carbonate an upper layer of alcohol is then usually formed. (The alcohol may be subsequently identified as the 3 5-dinitrobenzoate see Section 111,27,2.) Cool the residual alkahne mixture, and acidify it with dilute sulphuric acid. If no crystalline acid is precipitated, the acid may frequently be isolated by ether extraction, or it may be distilled from the acidified solution and isolated from (or investigated in) the distfllate. (The acid may be subsequently identified, e.g., as the S benzyl wo-thiuronium salt see Section 111,85,2.)... 

It is not only the solid state of a drug that suffers from ambiguities, but also the aqueous state. The state relevant for the intrinsic solubility is the state of the saturated solution of the neutral species. Since most aqueous drug solubilities are small, direct interactions of the drug molecules are usually rare. Hence, this state is usually very similar to the state of the drug at infinite dilution in water. Most computational methods disregard saturation effects. Usually this is a good approximation, but one should keep in mind that this approximation may result in some moderate, but systematic errors at the upper end of the solubility scale. 

Where the compounds have extremely low solubility, pKa values may be measured by the solubility method. An aqueous solution of a substance is titrated in the direction of its neutral species tmtil the free base or free acid is precipitated. pfCa can then be calculated from the solubility product. This method is not very accurate but may be used on very dilute solutions. 

Early classical extraction methods for PAs were applied without much consideration of the range of chemical structures of the alkaloids and in particular were not optimized to obtain the maximum yields of both the tertiary and oxide forms. In fact few publications even today describe the recovery achieved with the extraction procedure used. PAs have either a reduced tertiary nitrogen atom with a characteristic basic function or an oxidized form (PANO). Both forms have little solubility in non-polar solvents such as hexane and are best extracted with polar solvents such as methanol or with aqueous dilute acid. These solvents dissolve both the PAs and the PANOs with relative ease. 

Since the silver salts of the carboxylic acids are usually soluble in dilute nitric acid, they must be prepared by treating an aqueous solution of a neutral salt of the acid (and not the free acid itself) with silver nitrate solution. It is not practicable to attempt to neutralise the acid with sodium or potassium hydroxide solution, because the least excess of alkali would subsequently cause the white silver salt to be contaminated with brown silver oxide. The general method used therefore to obtain a neutral solution j to dissolve the acid in a small excess of ammonia solution, and then to boil the solution until all free... 

Method 2. Place a 3 0 g. sample of the mixture of amines in a flask, add 6g. (4-5 ml.) of benzenesulphonyl chloride (or 6 g. of p-toluenesulphonyl chloride) and 100 ml. of a 5 per cent, solution of sodium hydroxide. Stopper the flask and shake vigorously until the odour of the acid chloride has disappeared open the flask occasionally to release the pressure developed by the heat of the reaction. AUow the mixture to cool, and dissolve any insoluble material in 60-75 ml. of ether. If a solid insoluble in both the aqueous and ether layer appears at this point (it is probably the sparingly soluble salt of a primary amine, e.g., a long chain compound of the type CjH5(CH2) NHj), add 25 ml. of water and shake if it does not dissolve, filter it off. Separate the ether and aqueous layers. The ether layer will contain the unchanged tertiary amine and the sulphonamide of the secondary amine. Acidify the alkaline aqueous layer with dilute hydrochloric acid, filter off the sulphonamide of the primary amine, and recrystaUise it from dilute alcohol. Extract the ether layer with sufficient 5 per cent, hydrochloric acid to remove all the tertiary amine present. Evaporate the ether to obtain the sulphonamide of the secondary amine recrystaUise it from alcohol or dilute alcohol. FinaUy, render the hydrochloric acid extract alkaline by the addition of dilute sodium hydroxide solution, and isolate the tertiary amine. 

Niobic Acid. Niobic acid, Nb20 XH2O, includes all hydrated forms of niobium pentoxide, where the degree of hydration depends on the method of preparation, age, etc. It is a white insoluble precipitate formed by acid hydrolysis of niobates that are prepared by alkaH pyrosulfate, carbonate, or hydroxide fusion base hydrolysis of niobium fluoride solutions or aqueous hydrolysis of chlorides or bromides. When it is formed in the presence of tannin, a volurninous red complex forms. Freshly precipitated niobic acid usually is coUoidal and is peptized by water washing, thus it is difficult to free from traces of electrolyte. Its properties vary with age and reactivity is noticeably diminished on standing for even a few days. It is soluble in concentrated hydrochloric and sulfuric acids but is reprecipitated on dilution and boiling and can be complexed when it is freshly made with oxaHc or tartaric acid. It is soluble in hydrofluoric acid of any concentration. 

Dilution with water reverses the reaction, and heating the solution Hberates sulfur dioxide. Upon being added to a solution of teUurides, teUurium forms colored polyteUurides. Unlike selenium, teUurium is not soluble in aqueous sodium sulfite. This difference offers a method of separating the two elements. Like selenium, teUurium is soluble in hot alkaline solutions except for ammonium hydroxide solutions. Cooling reverses the reaction. Because teUurium forms solutions of anions, Te , and cations, Te" ", teUurium films can be deposited on inert electrodes of either sign. 

All stated pK values in this book are for data in dilute aqueous solutions unless otherwise stated, although the dielectric constants, ionic strengths of the solutions and the method of measurement, e.g. potentiometric, spectrophotometric etc, are not given. Estimated values are also for dilute aqueous solutions whether or not the material is soluble enough in water. Generally the more dilute the solution the closer is the pK to the real thermodynamic value. The pK in mixed aqueous solvents can vary considerably with the relative concentrations and with the nature of the solvents. For example the pK values for V-benzylpenicillin are 2.76 and 4.84 in H2O and H20/EtOH (20 80) respectively the pK values for (-)-ephedrine are 9.58 and 8.84 in H2O and H20/Me0CH2CH20H (20 80) respectively and for cyclopentylamine the pK values are 10.65 and 4.05 in H2O and H20/EtOH (50 50) respectively. pK values in acetic acid or aqueous acetic acid are generally lower than in H2O. 

Most organic substances can be dissolved readily in a suitable organic solvent and some are directly soluble in water or can be dissolved in aqueous solutions of acids (basic materials) or of alkalis (acidic materials). Many inorganic substances can be dissolved directly in water or in dilute acids, but materials such as minerals, refractories, and alloys must usually be treated with a variety of reagents in order to discover a suitable solvent in such cases the preliminary qualitative analysis will have revealed the best procedure to adopt. Each case must be considered on its merits no attempt at generalisation will therefore be made. It is however of value to discuss the experimental technique of the simple process of solution of a sample in water or in acids, and also the method of treatment of insoluble substances. 

With chemical treatment, the natural surfactants in crude oil can be activated [1384]. This method has been shown to be effective for highly viscous crude oil from the Orinoco Belt that has been traditionally transported either by heating or diluting. The precursors to the surfactants are preferably the carboxylic acids that occur in the crude oil. The activation occurs by adding an aqueous buffer solution [1382,1383]. The buffer additive is either sodium hydroxide in combination with sodium bicarbonate or sodium silicate. Water-soluble amines also have been found to be suitable [1506]. 

Polycarboxylated polyalkoxylates and their sulfate derivatives may be prepared by reacting an ethoxylated or propoxylated alcohol with a water-soluble, alkali or earth alkali metal salt of an unsaturated carboxylic acid [339]. The reaction occurs in aqueous solution in the presence of a free radical initiator and gives products of enhanced yield and reduced impurity levels, compared with the essentially anhydrous reactions with free carboxylic acids, which have been used otherwise. The method provides products that give solutions that are clear on neutralization, remain clear and homogeneous on dilution, and are useful as cleaning agents in drilling and other oil field operations. 

Since many new substances of interest are very poorly soluble in water, the assessment of the pKa in aqueous solution can be difficult and problematic. Potentiometry can be a quick technique for such assessment, provided the solubility of the substance is at least 100 pM. (Solutions as dilute as 10 pM can still be analyzed, but special attention must be given to electrode calibration, and ambient carbon dioxide must be excluded.) If the substance is soluble to only 1-10 pM and possesses a pH-sensitive UV chromophore, then spectrophotometry can be applied. CE methods may also be useful since very small sample quantities are required, and detection methods are generally quite sensitive. 

These dyes have affinity for one or, usually, more types of hydrophobic fibre and they are normally applied by exhaustion from fine aqueous dispersion. Although pure disperse dyes have extremely low solubility in cold water, such dyes nevertheless do dissolve to a limited extent in aqueous surfactant solutions at typical dyeing temperatures. The fibre is believed to sorb dye from this dilute aqueous solution phase, which is continuously replenished by rapid dissolution of particles from suspension. Alternatively, hydrophobic fibres can absorb disperse dyes from the vapour phase. This mechanism is the basis of many continuous dyeing and printing methods of application of these dyes. The requirements and limitations of disperse dyes on cellulose acetate, triacetate, polyester, nylon and other synthetic fibres will be discussed more fully in Chapter 3. Similar products have been employed in the surface coloration of certain thermoplastics, including cellulose acetate, poly(methyl methacrylate) and polystyrene. 

Hexammino - cobaltic Chloride, or Luteo-cobaltic Chloride, [Co(NH3)8]Cl3.—Several methods of preparation have been described. The best method is that of Jorgensen,1 whereby the salt is prepared by warming chloro-pentammino-cobaltic chloride, [Co(NH3)5C l]Cl2. in a pressure flask with 20 per cent, aqueous ammonia and ammonium chloride for several hours with constant shaking. After cooling, the mixture is removed from the flask and ammonia allowed to evaporate. The liquid is then diluted, hydrochloric acid added, and the whole heated on the water-bath, thus changing any aquo-pentammino-chloride into ehloro-pentammino-ehloride. More concentrated hydrochloric acid is added and the mixture cooled and filtered. The residue on the filter consists of ammonium chloride, chloro-pentammino-chloride, and hexammino-cobaltic chloride. Ammonium chloride is removed by treating with a 20 per cent, solution of hydrochloric acid, and the residue is then treated on a filter with cold water in which chloro-pentammino-cobaltic chloride is insoluble and hexammino-cobaltic chloride soluble. The salt is precipitated from its warm solution by the addition of half its volume of concentrated hydrochloric acid. 

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