Carboxylic acids, solvent partition

Carboxylic acids, solvent partition, 29 145-147 and dimerization, 29 145-147 Carboxypeptidase A, 22 409-421 active site, 22 418 catalytic mechanism, 22 416-421 chemical properties vs. Structure, 22 417-419... 

ABA is a carboxylic acid which at pH 3.0 partitions readily into organic solvents such as diethyl ether and ethyl acetate. The molecule has one asymmetric carbon atom at C-l and exhibits therefore optical activity. The naturally occurring enantiomer is dextrorotatory and has a sinister (S) configuration (Figure 1). 

To a solution of 5-hydroxy-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid methyl ester (4 g, 23.5 mmol) in CH2CI2 (100 ml) was added N,N -diisopropylethylamine (12.3 ml, 70.5 mmol) followed by chloromethyl methyl ether (3.6 ml, 47 mmol, distilled from tech, grade). The solution was refluxed for 3.5 h and the solvent was evaporated. The residue was partitioned between ethyl acetate (200 ml) and water (200 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic extracts were washed with saturated NaCI (100 ml), dried (MgS04), filtered, and evaporated to afford 4.9 g of a solid residue of 5-methoxymethoxy-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid methyl ester which was of suitable purity to use directly in the next step melting point 62°-65°C (crude) melting point 64°-66°C (diethyl ether/hexane). 

In the solvent extraction of metal ions with carboxylic acids, it is indispensable to have information about the partition of the carboxylic acid between the aqueous and organic phases. The carboxylic acid is known to dimerize in nonsolvating solvents. 

The partition of a carboxylic acid HA into an organic solvent is written as... 

Values of log Kv increase with increasing carbon number in carboxylic acids. The increment of log KD for an added methylene group is mainly due to the volume contribution of the methylene group to the partition, and thus it varies little from solvent to solvent, i.e., A log tfD/CH2 = 0.56-0.64 (21, 31, 141). The different AlogifD/CH2 values for different solvents are ascribable to the different solute-solvent interactions, and have been discussed elsewhere in more detail (31). 

The dimerization constants of carboxylic acids determined by the partition method are usually lower than the values obtained by IR spectroscopy, cryoscopy, or dielectric measurements (100). The correction for hydration gives dimerization constants expected from values in dry solvents by spectroscopic or dielectric measurements (29, 30). 

Reversed-phase high-performance liquid chromatography (RP-HPLC) is the usual method of choice for the separation of anthocyanins combined with an ultraviolet-visible (UV-Vis) or diode-array detector (DAD)(Hebrero et al., 1988 Hong et ah, 1990). With reversed-phase columns the elution pattern of anthocyanins is mainly dependent on the partition coefficients between the mobile phase and the Cjg stationary phase, and on the polarity of the analytes. The mobile phase consists normally of an aqueous solvent (water/carboxylic acid) and an organic solvent (methanol or acetonitrile/carboxylic acid). Typically the amount of carboxylic acid has been up to 10%, but with the addition of a mass spectrometer as a detector, the amount of acid has been decreased to as low as 1 % with a shift from trifluoroacetic acid to formic acid to prevent quenching of the ionization process that may occur with trifluoroacetic acid. The acidic media allows for the complete displacement of the equilibrium to the fiavylium cation, resulting in better resolution and a characteristic absorbance between 515 and 540 nm. HPLC separation methods, combined with electrochemical or DAD, are effective tools for anthocyanin analysis. The weakness of these detection methods is a lack of structural information and some nonspecificity leading to misattribution of peaks, particularly with electrochemical... 

In addition to intramolecular effects, intermolecular interactions have been shown to modify the observed partition coefficient. These include association of polar molecules in apolar systems, or dissociation of acids (e.g., carboxylic acids or pro-tonated forms of amines, which are the conjugated acids of the amines). The analysis of these effects has been presented in an explicit form (136, 149, 150). A distinction has to be made however, between the types of intermolecular interactions. Association of neutral polar molecules in apolar solvents may influence the observed partition coefficient, but there is little doubt that the monomer is the compound that influences the biological activity through its interaction with the biological system. 

Some exceptions have been encountered where partition coefficients, between water and two non-aqueous solvents, do not run parallel. A common example is the solute that forms a hydrogen bond with one non-aqueous solvent but not with the other, e.g. phenol with oleyl alcohol but not with dodecane (Burton, Clarke and Gray, 1964). Similarly, carboxylic acids form dimers in hydrocarbons, but not in moist alcohols (Biagi, etal., 1974). 

Most essential oils are complex mixtures of terpenic and sesquiterpenic hydrocarbons and their oxygenated terpenoid and sesquiterpenoid derivatives (alcohols, aldehydes, ketones, esters, and occasionally carboxylic acids), as well as aromatic (benzenoid) compounds such as phenols, phenolic ethers, and aromatic esters. So-called terpeneless and sesquiterpeneless essential oils are commonly used in the avor industry. Many terpenes are bitter in taste, and many, particularly the terpenic hydrocarbons, are poorly soluble or even completely insoluble in water-ethanol mixtures. Since the hydrocarbons rarely contribute aitything of importance to their avoring properties, their removal is a commercial necessity. They are removed by the so called washing process, a method used mostly for the treatment of citrus oils. This process takes advantage of the different polarities of individual essential oil constituents. The essential oil is added to a carefully selected solvent (usually a water-ethanol solution) and the mixture partitioned by prolonged stirring. This removes some of the more polar oil constituents into the water-ethanol phase (e.g., the solvent phase). Since... 

In modem medicine, mily the purified opium alkaloids and their derivatives are commonly employed. Although the ripe poppy capsule can contain up to 0.5 % total alkaloids, opium represents a much concentrated form and up to 25 % of its mass is composed of alkaloids. Of the many (>40) alkaloids identified, some six represent almost all of the total alkaloid content. Actual amounts vary widely, e.g., morphine (4-21 %), codeine (0.8-2.5 %), thebaine (0.5-2.0 %), papaverine (0.5-2.5 %), noscapine (narcotine) (4—8 %), and narceine (0.1-2 %). A t3q>ical commercial sample of opium would probably have a morphine content of about 12 %. Powdered opium is standardized to contain 10 % of anhydrous morphine, usually by dilution with an approved diluent, e.g., lactose or cocoa husk powder. The alkaloids are largely combined in salt form with meconic acid, opium containing some 3-5 % of this material. Meconic acid is invariably found in opium but, apart from its presence in other Papaver species, has not been detected elsewhere. It gives a deep red-colored complex with ferric chloride, and this has thus been used as a rapid and reasonably specific test for opium. Of the main opium alkaloids, only morphine and narceine display acidic properties, as well as the basic properties due to the tertiary amine. Narceine has a carboxylic acid function, while morphine is acidic due to its phenolic hydroxyl. This acidity can be exploited for the preferential extraction of these alkaloids (principally morphine) from an organic solvent by partitioning with aqueous base (Table 15.6). 

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