Purification, general acids

The first hypothesis of an in-situ reduction of acetonitrile and propionitrile in the presence of 1 to 4 and 5 suggested that one might be able to use this approach as a new synthetic route to this class of heterocyclics. Hexahydropyrimidines are conventionally prepared by condensation of aldehydes or ketones with 1,3-diamines (4). Water is a by-product in these reactions and must be removed either to favor the imine or enamine equilibrium or for product purification. Generally, the condensation is acid or base catalyzed and run in solvents (6). In some cases... 

The major disadvantage of solid-phase peptide synthesis is the fact that ail the by-products attached to the resin can only be removed at the final stages of synthesis. Another problem is the relatively low local concentration of peptide which can be obtained on the polymer, and this limits the turnover of all other educts. Preparation of large quantities (> 1 g) is therefore difficult. Thirdly, the racemization-safe methods for acid activation, e.g. with azides, are too mild (= slow) for solid-phase synthesis. For these reasons the convenient Menifield procedures are quite generally used for syntheses of small peptides, whereas for larger polypeptides many research groups adhere to classic solution methods and purification after each condensation step (F.M. Finn, 1976). 

Manufacture and Uses. Acetoacetic esters are generally made from diketene and the corresponding alcohol as a solvent ia the presence of a catalyst. In the case of Hquid alcohols, manufacturiag is carried out by continuous reaction ia a tubular reactor with carefully adjusted feeds of diketene, alcohol, and catalyst, or alcohol—catalyst blend followed by continuous purification (Fig. 3). For soHd alcohols, an iaert solvent is used. Catalysts used iaclude strong acids, tertiary amines, salts such as sodium acetate [127-09-3], organophosphoms compounds, and organometaHic compounds (5). 

Modem commercial wet-acid purification processes (see Fig. 4) are based on solvents such as C to Cg alcohols, ethers, ketones, amines, and phosphate esters (10—12). Organic-phase extraction of phosphoric acid is accompHshed in one or more extraction columns or, less frequently, in a series of countercurrent mixer—settlers. Generally, 60—75% of the feed acid P2 s content is extracted into the organic phase as H PO. The residual phosphoric acid phase (raffinate), containing 25—40% of the original P2O5 value, is typically used for fertilizer manufacture such as triple superphosphate. For this reason, wet-acid purification units are almost always located within or next to fertilizer complexes. 

The cmde dimethyl terephthalate is recovered and purified by distillation in most processes. Although distillation (qv) is generally a powerful separation technique, the mode of production of the terephthaHc acid determines its impurity content, which in turn may make purification by distillation difficult. Processes resulting in the alteration of the impurities by catalytic treatment have been developed so that distillation can perform the necessary purification. 

In general, plants using SO2 gas derived from metallic sulfides, spent acids, or gypsum anhydrite purify the gas stream before drying it by cold, ie, wet, gas purification. Various equipment combinations including humidification towers, reverse jet scmbbers, packed gas cooling towers, impingement tray columns and electrostatic precipitators are used to clean the gas. 

In the case of low temperature tar, the aqueous Hquor that accompanies the cmde tar contains between 1 and 1.5% by weight of soluble tar acids, eg, phenol, cresols, and dihydroxybenzenes. Both for the sake of economics and effluent purification, it is necessary to recover these, usually by the Lurgi Phenosolvan process based on the selective extraction of the tar acids with butyl or isobutyl acetate. The recovered phenols are separated by fractional distillation into monohydroxybenzenes, mainly phenol and cresols, and dihydroxybenzenes, mainly (9-dihydroxybenzene (catechol), methyl (9-dihydtoxybenzene, (methyl catechol), and y -dihydroxybenzene (resorcinol). The monohydric phenol fraction is added to the cmde tar acids extracted from the tar for further refining, whereas the dihydric phenol fraction is incorporated in wood-preservation creosote or sold to adhesive manufacturers. Naphthalene Oils. Naphthalene is the principal component of coke-oven tats and the only component that can be concentrated to a reasonably high content on primary distillation. Naphthalene oils from coke-oven tars distilled in a modem pipe stiU generally contain 60—65% of naphthalene. They are further upgraded by a number of methods. 

Because of their zwitterionic nature, amino acids are generally soluble in water. Their solubility in organic solvents rises as the fat-soluble portion of the molecule increases. The likeliest impurities are traces of salts, heavy metal ions, proteins and other amino acids. Purification of these is usually easy, by recrystallisation from water or ethanol/water mixtures. The amino acid is dissolved in the boiling solvent, decolorised if necessary by boiling with Ig of acid-washed charcoal/lOOg amino acid, then filtered hot, chilled, and set aside for several hours to crystallise. The crystals are filtered off, washed with ethanol, then ether, and dried. 

Amino acids have high melting or decomposition points and are best examined for purity by paper or thin layer chromatography. The spots are developed with ninhydrin. Customary methods for the purification of small quantities of amino acids obtained from natural sources (i.e. l-5g) are ion-exchange chromatography (see Chapter 1). For general treatment of amino acids see Greenstein and Winitz [The Amino Acids, Vols 1-3, J.Wiley Sons, New York 1961] and individual amino acids in Chapters 4 and 6. 

The most common method of purification of inorganic species is by recrystallisation, usually from water. However, especially with salts of weak acids or of cations other than the alkaline and alkaline earth metals, care must be taken to minimise the effect of hydrolysis. This can be achieved, for example, by recrystallising acetates in the presence of dilute acetic acid. Nevertheless, there are many inorganic chemicals that are too insoluble or are hydrolysed by water so that no general purification method can be given. It is convenient that many inorganic substances have large temperature coefficients for their solubility in water, but in other cases recrystallisation is still possible by partial solvent evaporation. 

Polypeptides. These are a string of a-amino acids usually with the natural 5(L) [L-cysteine is an exception and has the R absolute configuration] or sometimes "unnatural" 7f(D) configuration at the a-carbon atom. They generally have less than -100 amino acid residues. They can be naturally occurring or, because of their small size, can be synthesised chemically from the desired amino acids. Their properties can be very similar to those of small proteins. Many are commercially available, can be custom made commercially or locally with a peptide synthesiser. They are purified by HPLC and can be used without further purification. Their purity can be checked as described under proteins. 

---