Number of recrystallizations

Fig. 4a. Resolution of racemic (67) by column chromatography on microcrystalline cellulose triacetate (column B) and by recrystallization 35) C = crystals M = mother liquor the index following C or M gives the number of recrystallizations the fraction has undergone. The value of [ot] ° is given, followed by the quantity obtained...

Figure 2.9 Response surface showing an inherently continuous response (percent purity of a protein) as a function of an inherently discrete factor (number of recrystallizations).

The discrete factor number of recrystallizations is naturally ordered (see Figure 2.9). It obviously makes sense to plot yield against the number of recrystallizations in the order 1, 2, 3, 4, 5, 6, 7, 8, 9 it would not make sense to plot the yield against a different ordering of the number of recrystallizations, say 3, 7, 5, 8, 2, 1, 4, 9, 6. Other discrete factors are not always as meaningfully ordered, especially if they are... 

Laboratory Record. The working directions, in the section entitled procedure, are to be kept at hand while carrying out the manipulations. These directions do not need to be copied in the laboratory note book but it is essential, nevertheless, to keep a laboratory record in which are entered all important observations and data, such, for example, as appearance of solutions (color, turbidity) appearance of precipitates or crystals (color, size of grains, crystalline form) results of all weighings or measurements number of recrystallizations results of test for purity of materials and products, etc. 

Target/fu notion Resolving agent (number of recrystallization steps) Yield of crystalline diastereomeric salt (%) Configuration or optical rotation sign of resolved enantiomer ee or optical purity (op) (%) Reference... 

The total overall )deld of pure acid form the crude depends on the amount of crude acid taken, the care exercised to avoid material losses, and the number of recrystallizations required to attain the desired purity. Without recoveries from mother liquors, 100 g. of crude add, after conversion to the ammonium salt, and three recrystallizations of the latter, gave 40-45 g. of pure acid. Overall recovery of pure acid from 100 g. of the crude gave 50 g. of pure acid melting at 187-188°, 10 g. of less pure acid melting at 184-186°, and about 10 g. of a tarry solid residue. 

The effects of the preparation methods and the number of recrystallization were examined experimentally by the use of the threonine (TTir.) - water system. The supersaturation of D-77tr., for example, will slightly increase during the crystallization of L-Thr since for this system a < 2. This may lead to a conclusion that the possibility of primary nucleation to occur would also slightly increase as the progress of the resolution. Small stirred tank crystallizers were used both for preparation of... 

Fig.ll Effects of the number of recrystallization on purity drop occurrence... 

Amino alcohols can be resolved by a number of pathways including hydrolysis, esterification, and transesterification. For example, hydrolysis of Ai,0-diacet5l-2-amino-l-butanol with PPL followed by recrystallization results in (80a) with 95% ee (108). Hydrolysis of racemic acetates or butyrates of 2-[(aLkoxycarbonyl)amino]-l-aLkanols with PFL gives (R)-alcohol (81) with 95% ee (109). (3)-(81) can be obtained by transesterification of the racemic (81) with ethyl acetate which also serves as the reaction medium (109). 

The p-methoxybenzylidene ketal can be prepared by DDQ oxidation of a p-methoxybenzyl group that has a neighboring hydroxyl. This methodology has been used to advantage in a number of syntheses. " In one case, to prevent an unwanted acid-catalyzed acetal isomerization, it was necessary to recrystallize the DDQ and use molecular sieves. The following examples serve to illustrate the reaction " ... 

The filtrates are combined, cooled, and extracted with three successive 200 cc portions of ether. The pH of the filtrate is then raised to 3.5 with sodium hydroxide and the filtrate extracted with six successive 200 cc portions of ether to yield the balance of the product. The crude para-aminobenzoic acid product is recovered by evaporation of ether and is suspended in hot benzene, cooled and filtered to remove benzoic and toluic acids together with small amounts of impurities soluble in the filtrate. Recrystallization of the product from 200 cc of water yields 14.5 grams of light tan needles of para-aminobenzoic acid having an acid number of 411 (theoretical value 409). 

This is separated, washed with petroleum ether, and dried in vacuo. After some time it hardens into a whitish solid, which if it was prepared from a 1-bromo-pentane which had some of its isomer 3-bromo-pentane copresent with it has a melting point of about 80° to 83°C. However, by using a pure 2-bromo-pentane, and/or by recrystallizing a number of times from dilute alcohol, the melting point may be raised to 98° to 100°C, corrected. 

Proton magnetic resonance (CDC13) 8, number of protons, multiplicity, coupling constant J in Hz. 1.5-2.2 (2, multiple ), 2.7-3.0 (4, multiplct), 7.0 (1, doublet, J = 2.5), 7.1-7.5 (6, multiplet), 7.7-8.2 (4, multiplet). A sample recrystallized from methanol-chloroform melted at 183-185°. The submitters also obtained pure product, m.p. 181-183°, after chromatography on basic alumina with 20% petroleum ether in dichloromethane as eluent. 

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