Solvent extraction equilibria neutral extractants

The fermentation broth typically contains 20-30 mg/L of antibiotics, which is to say 30 parts per billion, and must be extracted into concentrated form using solvent extraction. The solvent extraction method was developed by Shell Oil and by Podbielniack and is based on the principle that penicillin is hydrolyzed in aqueous medium to H+ and RCOO ions. Thus, equilibrium in an acidic medium (i.e., one with low pH or high H+ concentration) is favored by the neutral RCOOH form, whereas equilibrium in an alkaline medium (i.e., one with high pH or low H+ concentration) is favored by the RCOO ionic form. The neutral form is more soluble in an organic medium, and the ionic form is more soluble in an aqueous medium. Thus, with amyl acetate as the organic solvent the partition coefficient of penicillin between solvent and water is about 100 at pH 3 and about 1 at pH 6. In the industrial process, the aqueous broth was acidified to pH 3 for the extraction into the organic solvent, and alkalized to a pH 6 for reverse extraction back into an aqueous medium. 

The thermodynamic data for the adduct formation equilibrium between uranyl chelates and neutral donors (Eq. 17) were evaluated from the solvent extraction data90,91 obtained at different temperatures and these are given in Table 23. It is seen that these adducts are mainly enthalpy stabilized and this is expected when the neutral donor is directly coordinated to the metal ion. However, caution should be exercised in interpreting such data since the diluent used is known to influence thermodynamic parameters appreciably215. ... 

Bisulfite addition products are readily formed at wine pHs (1, 23, 24). The bisulfite addition product is thought to be a more sensory-neutral compound and may be exploited by winemakers as a means of decreasing the aldehydic character of wines (1). Bisulfite addition has also been used to mask the stale flavor of beer which is thought to be largely due to the formation of trans-l-noneml (25). Kaneda et al. (25) used HPLC with fluorescent detection of an o-phthalaldehyde derivative to quantitate and identify individual aldehyde-bisulfite products, however, only acetaldehyde-bisulfite adducts were observed in commercial beers with this method. Hydrolysis of the adducts occurs at pHs greater than 8, therefore by adjusting the pH prior to analysis, total aldehydes (free plus bisulfite bound) can be estimated. At low pHs accurate estimation of free aldehydes is complicated however, by analysis conditions which alter the equilibrium between bound and free forms (temperature, dilution, solvent extraction, analysis time, etc.). 

The complex compounds formed by the metal cations in solvent extraction systems are illustrated first by the formation of complex compounds between cations and neutral molecules in aqueous solution. An example of an equilibrium reaction involving such formation is [P2]... 

Neutral extractants constitute the third important class of solvent extraction reagents for the rare-earth elements. Since they have no charge, neutral extractants only extract neutral complexes or charge-balanced ion pairs. They also tend to extract ion-paired acid molecules such as HNO3. Solvating extractants may be dissolved in an organic diluent, or they may be the organic diluent itself (e.g., diethylether, methylisobutylketone, tributyl-phosphate). Phase transfer is accomplished by solvation of the complex by the extractant, and a typical equilibrium can be written as... 

Generally, it has been found that the organic acids and bases do exist in aqueous solution as equilibrium mixtures of their respective neutral as well as ionic forms. Thus, these neutral and ionic forms may not have the same identical partition coefficients in a second solvent therefore, the quantity of a substance being extracted solely depends upon the position of the acid-base equilibrium and ultimately upon the pH of the resulting solution. Hence, extraction coefficient (E) may be defined as the ratio of the concentrations of the substance in all its forms in the two respective phases in the presence of equilibria and it can be expressed as follows ... 

Pertechnetate in neutral and alkaline media can be extracted into solutions of tetra-alkylammonium iodides in benzene or chloroform. With tetra-n-heptylammo-nium iodide (7.5 x 10 M) in benzene distribution coefficients up to 18 can be obtained . A solution of fV-benzoyl-iV-phenylhydroxylamine (10 M) in chloroform can be used to extract pertechnetate from perchloric acid solution with a distribution coefficient of more than 200, if the concentration of HCIO is higher than 6 M The distribution of TcO between solutions of trilauryl-ammonium nitrate in o-xylene and aqueous solutions of nitrate has been measured. In 1 M (H, Li) NOj and 0.015 M trilaurylammonium nitrate the overall equilibrium constant has been found to be log K = 2.20 at 25 °C. The experiments support an ion exchange reaction . Pertechnetate can also be extracted with rhodamine-B hydrochloride into organic solvents. The extraction coefficient of Tc (VII) between nitrobenzene containing 0.005 %of rhodamine-B hydrochloride and aqueous alcoholic " Tc solution containing 0.0025 % of the hydrochloride, amounts to more than 5x10 at pH 4.7 . 

Liquid-liquid extraction (LLE) has been around for a long time and has been used extensively as an analytical sample pretreatment to remove unwanted matrix components [16,17]. It is based on the principles of differential solubility and partitioning equilibrium of analyte molecules between aqueous (the original sample) and organic phases. Depicted in Fig. 5, LLE initially involves pH adjustment of the sample with an appropriate buffer. This pH adjustment is intended to neutralize the molecule, making it more amenable to extraction. The next step is the addition of an immiscible organic extraction solvent, followed by agitation... 

As if the low distribution coefficient does not present enough of an obstacle, extraction of acetic acid from fermentation broths is made still more unattractive by the high pH of the solutions. For the bioprocesses being evaluated, acetic acid will be produced in a solution with a pH of about 6.0. The pK of acetic acid is 4.8 and thus, at a pH of 6.0, virtually all the acetic acid produced in solution exists as an acetate ion. Current extraction/recovery schemes entail acidification (with HCl, for example) to convert the acetate ion to free acetic acid. Then the free acid can be extracted with an organic solvent. If CO2 IS used as the extractant, HCl is not required. Carbonic acid from the C02-water equilibrium will neutralize part, but not all, of the acetate ion this can be determined from a material and charge balance of species in solution. 

The five solvents just discussed extract uranium in the form of neutral complexes of uranyl nitrate. With TBP the complex-forming equilibrium is... 

Only the unionized form of a drug is extracted into the organic solvent. Therefore acidic drugs, which are unionized imder acidic conditions are extracted from acidified matrices into organic solvents basic drugs are likewise extracted from basified matrices. The optimal pH for acidic species is 1-2 pH units below their pK values, and for basic species it is 1-2 pH units above their pK values. Extraction can be difficult for compoimds which are soluble in water at all pH values, for example water-soluble amphoteric and neutral drugs. In some cases, the addition of buffer salts to the aqueous solution increases its ionic strength and hence its polarity. This tends to decrease the affinity of polar compoimds for the aqueous phase, and thus shifts the partition equilibrium in favor of extraction. 

Liquid-Liquid Extraction (LLE) The principle of LLE is based on the differential solubility and partitioning equilibrium of drug molecules between aqueous (sample) and organic phases. In many cases, pH adjustment with appropriate acids, bases, or buffer is necessary to neutralize the analyte molecules and enables a more efficient extraction. An immiscible organic solvent is added to the aqueous sample matrix, followed by vortex mixing to facilitate equilibrium partitioning of analyte molecules between the two phases. When the... 

The reaction is very efficient. If the hydrolysis is continuously titrated to pH 7.8 with sodium hydroxide about 96% of the penicillin G is hydrolysed to 6-AP A. This is close to the equilibrium position for a dilute solution (33 g dm ) of penicillin G. After the hydrolysis the enzyme is removed and the solution is acidified (pH 2.5). The phenylacetic acid released is extracted into a solvent (methylisobutylketone) and is recycled to the penicillin G fermentation (section 6.3.1). The crude solution of 6-APA which remains is then neutralized and concentrated until its concentration is between 120 and 150 g cm " At its isoelectric point (pH 4.3) it precipitates from this concentrate and the crystals are washed and dried. The overall yield of 6-APA is about 90% of theory. 

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