Stirred crystallization

Hydrolysis of benzyl cyanide to phenylacetamide. In a 1500 ml. three-necked flask, provided with a thermometer, reflux condenser and efficient mechanical stirrer, place 100 g. (98 ml.) of benzyl]cyanide and 400 ml. of concentrated hydrochloric acid. Immerse the flask in a water bath at 40°. and stir the mixture vigorously the benzyl cyanide passes into solution within 20-40 minutes and the temperature of the reaction mixture rises to about 50°, Continue the stirring for an additional 20-30 minutes after the mixture is homogeneous. Replace the warm water in the bath by tap water at 15°, replace the thermometer by a dropping funnel charged with 400 ml. of cold distilled water, and add the latter with stirring crystals commence to separate after about 50-75 ml. have been introduced. When all the water has been run in, cool the mixture externally with ice water for 30 minutes (1), and collect the crude phenylacetamide by filtration at the pump. Remove traces of phenylacetic acid by stirring the wet sohd for about 30 minutes with two 50 ml. portions of cold water dry the crystals at 50-80°. The yield of phenylacetamide, m.p. 154-155°, is 95 g. RecrystaUisation from benzene or rectified spirit raises the m.p. to 156°. 

Qui, Yangeng and Rasmusen, A.C., 1991. Nucleation and growth of succinic acid crystals in a batch stirred crystallizer. American Institute of Chemical Engineers Journal, 36, 665-676. 

Later, Thangaraj et al. (275,281) developed a novel, improved route (prehydrolysis method) for the preparation of good quality TS-1 samples. In this method the silica source (tetraethyl orthosilicate TEOS) in Ao-propanol was first hydrolyzed with 20% aqueous TPAOH solution prior to the (dropwise) addition of titanium butoxide in dry iso-propanol under vigorous stirring. Crystallization was done statically at 443 K for 1-5 days and the solid was calcined at 823 K for 10 h. The TS-1 samples thus obtained exhibited high catalytic activity in hydroxylation reactions. 

To a mixture of 10.5 g N-methyl formanilide and 11.9 g POCI3 that had incubated at room temperature for 0.5 h (it had become quite red in color) there was added 6.4 g of the solid ether, 1,2,4-triethoxybenzene. The mixture was heated on the steam bath for 2.5 h, then poured into 500 mL of shaved ice. After a few minutes stirring, crystals appeared. The reaction was allowed to stand for a few h, then... 

Kondepudi and McBride indicate that stirred crystallization is effective to accelerate the enantiomeric excess (ee) of crystals in the recrystallization step. [7] Kondepudi reported that the ee of the crystal greater than 95% can easily be obtained in stirred crystallization of achiral materials that crystallize in chiral form, such as sodium... 

Fig. 14 Histograms of the crystal enantiomeric excess cee = (NL - Nd)/(Nl + ND) of L-crystals for spontaneous chiral symmetry breaking in NaCICb crystallization a 63 independent unstirred crystallizations b 60 independent stirred crystallizations (Reproduced from [22]. Copyright 2001, American Chemical Society)...

Figure 9. Potential sources of contact nuclei in a stirred crystallizer (4).

Recrystallization. The suspension of crystals obtained above is centrifuged (20,000 r.p.m. at 0°) and the crystals are dissolved in M/30 phosphate buffer, pH 6.0, containing 5% of sodium chloride, to a concentration of about 30 mg. of protein/ ml. The protein dissolves slowly, but completely, in 1-2 hours. The concentration of ammonium sulfate is estimated with Nessler reagent." By adding a saturated solution of ammonium sulfate as above, the concentration is raised to s 0.23. The solution is then nucleated with /3-galactosidase crystals, and is further stirred. Crystals begin to appear after H hour, and the process is complete in 24-36 hours. The product has a specific activity of 575,000 yield, 65%. 

Very impure compounds typically do not crystallize well. Additionally, the target compound can oil out of solution if the solution reaches saturation above the melting point. Crystallizations for purification should be stirred. Crystallizations benefit by seeding with crystalline material therefore, it may be beneficial to purify a small amount of material by column chromatography to determine the melting point, and to have seeds before proceeding with a crystallization. 

Nonchiral cytosine when crystallized from methanol with stirring and without any seed yields powder-like crystals that either show a plus or minus Cotton-effect in the circular dichroism spectra (Kawasaki et al. 2008) Out of 55 stirred crystallizations, (+) cytosine formed 24 times, (—) cytosine 21 times, and ten samples were below the detection level (Fig. 3.5). 

Kondepudi D.K. Laudadio J. and Asakura K. (1999) Chiral symmetry breaking in stirred crystallization of 1,1 -binaphthyl melt, J. Amer. Chem. Soc. 121, 1448-1451. 

The induction time in homogeneous nucleation of a or p polymorphs of quizalofop-ethyl, i.e. the time the crystals first appeared in a supersaturated solution of quizalofop-e yl-ethanol mixtures was measured at temperatures between 293 and 31 IK in a batch stirred crystallizer. Experimental equations on the induction time have been derived semiquantitatively on the basis of an equation of classical nucleation rate. In addition, the concentration of supersaturated... 

The authors attribute the observed selectivity to an autocatalytic effect arising from the rapid production of secondary nuclei from a single primary nucleus in the stirred system. In essence, they propose that the first crystal to form will be either an L-crystal or o-crystal, each with 50% probability. When the solution is stirred, this ur-crystal (i.e., original crystal) serves as the template or the source for the formation of other crystals from solute brought to it by the stirring-induced transport in the supersaturated solution. In the absence of stirring, crystals form independently—there is no communication between crystals already formed and the rest of the solution, except for that provided by the relatively slow process of diffusion. 

Kondepudi, D. K. Sabanayagam, C. 1994. Secondary Nucleation that Leads to Chiral Symmetry Breaking in Stirred Crystallization, Chem. Phys. Lett. 217, 364-368. 

The crystals of naphthamide 3 used for the asymmetric reaction were prepared by stirred crystallization from the melt.22) The samples were completely melted at 120°C, which greatly exceeds their melting points (mp of 3b 110-112°C), cooled and solidified by lowering the temperature by stirring to 100°C. High reproducibility of both the chiral crystallization and asymmetric reaction was achieved by this method however, the direction of the optical rotation of the photoproduct was inconsistent and appeared randomly. Of course, the... 

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