Crystallization yield

Ewald summation was invented in 1921 [7] to permit the efl5.cient computation of lattice sums arising in solid state physics. PBCs applied to the unit cell of a crystal yield an infinite crystal of the appropriate. symmetry performing... 

The camphorquinone can be purified in either of two ways, (i) To save time, the drained but still damp material can be recrystallised from water containing 10% of acetic acid, the hot filtered solution being cooled and vigorously stirred. The quinone separates as brilliant yellow crystals (yield, 2 5 g.), m.p. 192-194 , increased to 196-197 by a second reciystal-lisation. (ii) The crude camphorquinone can be dried in a vacuum desiccator (weight of dry quinone, 5 g.), and then recrystallised from petroleum (b.p. 100-120 ), the hot solution being filtered through a fluted paper in a pre-heated funnel. The quinone separates in beautiful crystals, m.p. 196-197 , 2 8 g. 

A crystal yields when the force xh (per unit length) exceeds /, the resistance (a force per unit length) opposing the motion of a dislocation. This defines the dislocation yield strength... 

When crystals yield, dislocations move through them. Most crystals have several slip planes the f.c.c. structure, which slips on 111) planes (Chapter 5), has four, for example. Dislocations on these intersecting planes interact, and obstruct each other, and accumulate in the material. 

According to the submitters l-cyano-S-a-naphthylurea is obtained similarly from a-naphthyl isocyanate in 85-90% yields. Crystallization from acetone-petroleum ether (12 and 6 ml., respectively, per gram of crude product recovery approximately 60% per crystallization) yields lustrous prisms, m.p. 148-149 with decomposition. 

Further development of the column with 25% ethyl acetate in benzene produces 2.5 g of material, which on repeated crystallization yields 0.22 g of 17a,21-dihydroxypregn-4-ene-3,ll,20-trione 21-acetate mp 248-251°. Identity with cortisone acetate is established by a comparison of infrared spectra. Elution of the column with 30 % ethyl acetate in benzene gives after crystallization, 0.21 g of ll/9,17a,21-trihydroxypregn-4-ene-3,20-dione 21-acetate mp 219-222°. 

The term solubility thus denotes the extent to which different substances, in whatever state of aggregation, are miscible in each other. The constituent of the resulting solution present in large excess is known as the solvent, the other constituent being the solute. The power of a solvent is usually expressed as the mass of solute that can be dissolved in a given mass of pure solvent at one specified temperature. The solution s temperature coefficient of solubility is another important factor and determines the crystal yield if the coefficient is positive then an increase in temperature will increase solute solubility and so solution saturation. An ideal solution is one in which interactions between solute and solvent molecules are identical with that between the solute molecules and the solvent molecules themselves. A truly ideal solution, however, is unlikely to exist so the concept is only used as a reference condition. 

This relationship, of course, only gives the total mass of solids formed. To reveal how that solid matter is distributed across a crystal population, the other conservation equation considered in Chapter 2 viz. the population balance must be invoked. Firstly, however, the crystal yield is considered a little further. 

The first, and simplest, step in predicting crystallizer performance is the calculation of crystal yield. This can easily be estimated from knowledge of solution concentration and equilibrium conditions permitting calculation of the overall mass balance... 

The mixture was heated to reflux for 24 hours. The chloroformic reaction mixture was washed with water, and then dried over anhydrous sodium sulfate. The chloroform was evaporated off and the oil obtained was fractionally distilled under a pressure of 0.2 mm Hg. The fraction distilling at 140°C to 160°C, being the desired product indicated above, was collected and crystallized. Yield 94 g (32% of theory) MP 7B°C (after recrystallization in petroleum ether). 

The residual solid in the mother liquors is repeatedly and systematically crystallized, yielding a further fraction of 1-a-methylphenethylamine d-tartrate which may be purified by recrystallization. d-a-Methylphenethylamine may be readily recovered from the mother liquors by the addition of tartaric acid thereto for the formation of acid tartrates and separation of d-a-methylphenethylamine d-bitartrate by crystallization. 

After filtration and recrystallization from ethanol, there are obtained 5-(2-chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-cl -pyridine hydrochloride crystals (yield 60%) having a melting point (Koefler block) of 190°C. 

A mixture of 4.0 grams of N-methyl-3-toluidine and 2.8 grams of sodium hydrogencarbon-ate in 50 cc of acetone was stirred at 0° to 10°C and 7.4 grams of 2-naphthyl chlorothiono-formate was added in small portions thereto and the mixture was heated under reflux for 30 minutes. The cooled mixture was poured into about 150 cc of cold water and 2-naphthvl-N-methvl-N-(3-tolyl)thionocarbamate was obtained as white crystals. Yield is 9.1 grams (90 o). Recrystallization from alcohol gave colorless needle crystals, MP 110.5° to 111.5°C. 

A solution of 2-bromo-4-chloro-5-phenyl-2,3-dihydro-1-benzothiepin (1.02 g, 2.84 mmol) in THF (3 mL) was added in one portion to a solution of DBN (0.52 g, 4.2 mmol) in THF (3 mL) at rt. After stirring for 2h, the red mixture, containing some precipitate, was poured into 10% aq HC1 (20 mL) and the aqueous solution was extracted with CHCl, (2x15 mL). The combined extracts were washed with H20, dried (MgS04) and carefully concentrated in vacuo at subambient temperature. The yellow oil, which solidified on cooling, was chromatographed [alumina (Merck 71707,25 g), hexane] to give colorless crystals yield 0.58 g (76%) mp 87-88 °C. 

A mixture of 6-mesyl-6,7-dihydro-5/f-dibenz[ ,c]azepine (29, R = Ms 13.67 g, 50 mmol) in anhyd DMSO (160 mL) and t-BuOK (18.7 g, 165 mmol) was stirred for 45 min at 20 C under N2. Another portion of /-BuOK (2.65 g, 25 mmol) was added and stirring was continued for a further 45 min. The mixture was transferred to a separating funnel with ice-cold H20 (1.1 L) and extracted with Et20 (700 mL). The aqueous phase was extracted again with Et,0 (200 mL) and the combined ethereal extracts were then dried for 2 h (CaCl2) and evaporated to give the crude product as a pale-yellow oil (9.61 g, 99 %). which was purified bv distillation (bp 125 126/0.01 Torr) to give the product as colorless crystals yield 8.25 g (85 %) mp 84-85 C. 

Acridine-9-carbonitrile 10-oxide (la 3.00g, 13.6 mmol) in benzene (1.8 L) in a quartz immersion well was irradiated for 3 h with a Hanovia high-pressure 450-W Hg lamp equipped with a Pyrex filter. The resulting solution was evaporated under reduced pressure and the residue was extracted with pentane (3 x 50 mL). The combined extracts were evaporated under reduced pressure at 20 C to give orange crystals yield 1.8 g (60%) mp 105-109 C (Et20/pentane). 

Method B 2-Amino-4-tolyl 2-(methoxycarbonyl)phenyl sulfide (273 g, 1 mol) was heated at 215-230JC for 1 h under N2 and MeOII was allowed to distill off. The mixture was heated at this temperature under vacuum for a further 30 min, cooled to 100°C, diluted with EtOH (400 mL) and refluxed for 1 h. The mixture was cooled and the solid product was collected and recrystallized (EtOH, 400 mL), giving colorless crystals yield 217 g (90%) mp 288 -290 C. 

A mixture of the nitroso compound 39 (3.3 g. 10 mmol), hydrazine hydrate (3 mL, large excess), MeOH (30 mL) and THF (30 mL) was kept at 20 C for 1 h and then concentrated in vacuo. The residue was dissolved in warm CH2C12 and the solution was dried (Na2S04) and evaporated under reduced pressure to leave the product as pale-yellow crystals yield 2.5 g (83%) mp 288-290 C (CH2C12/Et20). 

A suspension of compound 10 (0.3 g, 1 mmol) in i-PrOH (2mL) containing TsOH (trace) was heated under reflux for 25 min. The product separated on cooling as pale-yellow crystals yield 0.2 g (70%) nip 129-133 C (i-PrOH). 

A solution of phenol (188 mg, 2 mmol) and benzonitrile (2.06 g, 20 mmol) in McCN (20 mL) was degassed by bubbling nitrogen through it and irradiated with a 16-W low-pressure mercury arc lamp (Applied Photophysics Ltd, APQ40) for 24h. The crude product was separated by flash chromatography (EtOAc/ petroleum ether 1 5) to give yellow crystals yield 79 mg (20%) mp 53-55 C. 

To the crude product 2 (1.1 g, 3.8 mmol) was added excess t-BuOK in t-BuOH (150mL). The mixture was warmed on a steam bath for 15 min, poured into H20 (300 mL), then extracted with Et20. The Et20 extract was washed with H20, dried (K2C03), and evaporated to dryness. Recrystallization of the residue from EtOH (20 mL) afforded 3 as yellow crystals yield 313 mg (39%) mp 135-138 C. 

A solution of dibenzo[c,g][l,2]diazocine (206 mg, 1 mmol) and barium hydroxide octahydrate (0.5 g, 1.68 mmol) inluxing EtOH (50 mL) was treated with powdered zinc (0.5 g). Afterluxing for a few minutes, the solution became colorless and heating was discontinued. Dry ice (ca. 5 g) was added in small portions and the resulting suspension was filtered. The filtrate was evaporated to 20 mL and cooled to 0 C to afford colorless crystals yield 82 ing (40%) mp 168-169 C (dec.). 

As an example for continuous process design, 2-keto-3-deoxy-D lycero-D-galacto-nonosouate (KDN) (S) has been produced on a 100-g scale from D-mannose and pyruvate using a pilot-scale EMR at a space-time yield of 375 gl d and an overall crystallized yield of 75% (Figure 10.6) [47]. Similarly, L-KDO (6) can be synthesized from L-arabinose [48]. 

Our approach for chiral resolution is quite systematic. Instead of randomly screening different chiral acids with racemic 7, optically pure N-pMB 19 was prepared from 2, provided to us from Medicinal Chemistry. With 19, several salts with both enantiomers of chiral acids were prepared for evaluation of their crystallinity and solubility in various solvent systems. This is a more systematic way to discover an efficient classical resolution. First, a (+)-camphorsulfonic acid salt of 19 crystallized from EtOAc. One month later, a diastereomeric (-)-camphorsulfonic acid salt of 19 also crystallized. After several investigations on the two diastereomeric crystalline salts, it was determined that racemic 7 could be resolved nicely with (+)-camphorsulfonic acid from n-BuOAc kinetically. In practice, by heating racemic 7 with 1.3equiv (+)-camphorsulfonic acid in n-BuOAc under reflux for 30 min then slowly cooling to room temperature, a cmde diastereomeric mixture of the salt (59% ee) was obtained as a first crop. The first crop was recrystallized from n-BuOAc providing 95% ee salt 20 in 43% isolated yield. (The optical purity was further improved to -100% ee by additional recrystallization from n-BuOAc and the overall crystallization yield was 41%). This chiral resolution method was more efficient and economical than the original bis-camphanyl amide method. 

Wayne Genck (7 8) has recently published several useful articles about batch crystallization. Often lab filtration after crystallization is done with a thin cake and no problem is observed. But when taken to the plant, this operation takes days to build and wash a cake. To avoid this problem it is best to operate a crystallizer that is properly seeded and cooled according to a profile that follows the equation in reference (7), slow at first and fastest at the end. The other reference (8) discusses the challenges without seeding. Experience by the author confirms that a large amount of seed crystal is required, about 1-2 % wt of the final crystal yield. 

The fragment ions at m/z 571,557,526,512,498, and 484 correspond to consecutive cleavages of 45 (COOIF), 59 (CHT OOIF) or 73 (CH2CH2COOH ) from M+ that are directly correlated with the heme structure. Hemin, synthetic (l-hematin (heme crystals), and parasite-derived heme crystals yield... 

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