Purification, general carboxylic

Analyses for the Saxitoxins. Early methods for analysis of the saxitoxins evolved from those used for toxin isolation and purification. The principal landmarks in the development of preparative separation techniques for the saxitoxins were 1) the employment of carboxylate cation exchange resins by Schantz et al. (82) 2) the use of the polyacrylamide gel Bio-Gel P2 by Buckley and by Shimizu (5,78) and 3) the development by Buckley of an effective TLC system, including a new solvent mixture and a new visualization technique (83). The solvent mixture, designated by Buckley as "E", remains the best for general resolution of the saxitoxins. The visualization method, oxidation of the saxitoxins on silica gel TLC plates to fluorescent degradation products with hydrogen peroxide and heat, is an adaptation of the Bates and Rapoport fluorescence assay for saxitoxin in solution. Curiously, while peroxide oxidation in solution provides little or no response for the N-l-hydroxy saxitoxins, peroxide spray on TLC plates is a sensitive test for all saxitoxin derivatives with the C-12 gemdiol intact. 

Liquid-liquid partitioning constitutes the most popular cleanup approach used for purification of residues of monobasic -lactam antibiotics. Such residues are generally extracted from the primary aqueous sample extracts by dichloromethane or chloroform under acidic conditions in which the ionization of their carboxylate moiety is suppressed, and then back-extracted into pH 7 phosphate buffers (84, 85, 89, 92, 95, 97, 99). In these instances, however, all analytical steps involving contact of the analytes with acids should be performed in a highly reproducible fashion and for a minimum length of time due to the instability of these compounds, especially penicillin G, in the acidic media employed. 

Physical Properties. The molecular weight of dalbaheptides ranges from about 1150 to 2200. Pure dalbaheptides are obtained as colorless or whitish amorphous powders that usually retain water and solvents. Dalbaheptides are generally water-soluble. Teicoplanin can be obtained as an internal sail or as a partial monoalkaline (sodium) salt depending on tile pH of the aqueous solution in the final purification step. Other dalbaheptides arc obtained as acidic salts, such as hydrochlorides (vancomycin, actaplanin) or sulfates (ristocetin A, avoparcin, eiemomycin). The presence of amino, carboxyl, benzylic, and phenolic hydroxyl functions, sugars, and aliphatic chains influences both water solubility and total charge. 

Application of halogenides under the same conditions results inMHal/OR), which does not decompose in excess of M OR or under refluxing. The patent [833] describes the general method of preparation of the stable metal alkoxide solutions (which are used in technology) it comprises a heterogeneous reaction of Zn, Cd, Y, Ln, In, Pb, Sn, Zr, Sb, Bi and Mn carboxylates in alcohol solutions with NH3 or amines with subsequent purification by ionic exchange. 

In practical terms, the purification of aqueous solutions of XX on Rohm and Haas macroreticular resin XAD-16 proved to be very efficient (95-98% recovery of material with a purity of approximately 95%) and economical to carry out. This chromatographic purification step removes salts (especially phosphates) introduced at earlier processing steps in Antibioticos plant (Schemes 1 and 2), thereby enabling us to minimize the amount of DDM needed to fully esterify both carboxyl groups of XX 2.3 to 2.5 moles DDM per mole of XX generally proved sufficient.31 Although DDM is a relatively stable molecule (see footnote 20), its separate preparation does introduce some safety concerns. In practical terms, it should be possible to prepare... 

Barton Esterification Reductive Decarboxylation. O-Acyl thiohydroxamates or Barton esters are useful precursors of carbon-centered radicals via thermolysis or photolysis. Several different methods are available for converting carboxylic acids into Barton esters (eq 1). These reactions generally proceed via the attack of a 2-mercaptopyridine-N-oxide salt on an activated carboxylic acid that has either been preformed (acid chloride, mixed anhydride) or generated in situ (with 1,3-dicyclohexylcarbodiimide or tri-n-butylphosphine + 2,2 -dithiodipyridine-l,r-dioxide). However, HOTT has the distinct advantages of (1) being easy to prepare and handle without the need for any special precautions, (2) facilitates efficient Barton esterification of carboxylic acids, and (3) simplifies subsequent work-up and purifications by avoiding the need to remove by-products like 1,3-dicyclohexylurea. 

The described two-step procedure is uncomplicated and can be carried out in 1 day to give in good yield a product that does not require any further purification. This procedure has been used for the preparation of 3-methyl-, 9-methyl-, and 6-methoxy-l,2,3,4-tetrahydro-j3-carboline and has been modified to obtain 9-phenyl-l,2,3,4-tetrahydro-j3-carboline. The method is generally applicable to the preparation of other 1-unsubstituted tetrahydro-/3-carbolines providing the 1-carboxylic acid precursor is not insoluble in the hot acid used to effect decarboxylation. 

When treated with concentrated alkali, acetoacetic ester is converted into two moles of sodium acetate, (a) Outline all steps in a likely mechanism for this reaction. (Hint See Sec. 21.11 and Problem 5.8, p. 170.) (b) Substituted acetoacetic esters also undergo this reaction. Outline the steps in a general synthetic route from acetoacetic ester to carboxylic acids, (c) Outline the steps in the synthesis of 2-hexanone via acetoacetic ester. What acids will be formed as by-products Outline a procedure for purification of the desired ketone. (Remember that the alkylation is carried out in alcohol that NaBr is formed that aqueous base is used for hydrolysis and that ethyl alcohol is a product of the hydrolysis.)... 

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