Recrystallization spontaneous

Cyclohexene (8 g, 0.097 mole) is added to a mixture of 105 g of 98-100% formic acid and 13 g (0.115 mole) of 30 % hydrogen peroxide contained in a 250-ml flask fitted with a reflux condenser. The two layers are shaken together briefly, whereupon spontaneous heating occurs. The mixture becomes homogeneous at 65-70°, this temperature being maintained for 2 hours on a steam bath. The formic acid is removed by distillation under reduced pressure. The residue is mixed with 50 ml of 6 A sodium hydroxide and heated on a steam bath for 45 minutes. The solution is cooled, neutralized with hydrochloric acid and evaporated to dryness under vacuum. The solid residue is distilled, affording about 10 g of the product, bp 128-132°/15 mm. The distillate solidifies and may be recrystallized from acetone, giving about 70% of // a -l,2-cyclohexanediol, mp 102-103°. 

To a solution of 17.2g (0.10 mol) of 3-bromopropionyl chloride in 100 ml of anhydrous benzene was added dropwise with stirring a solution of 8.6 g (0.10 mol) of anhydrous piperazine in 20 ml of dry chloroform over a period of 30 minutes. The temperature rose spontaneously to 45°C during the addition. After the temperature ceased to rise, stirring was continued for another hour. The reaction mixture was then filtered to remove the piperazine hydrochloride by-product. The filtrate was evaporated to dryness and the residue recrystallized from ethanol to obtain the desired N,N -bis-(3-bromopropionyl) piperazine as a white crystalline sol id melting at 103°C to 104°C. The identity of the product was further established by elemental analysis. 

The aqueous layer Is separated and washed with ether, the ether extracted with 5% hydrochloric acid, the acidic solution is made basic with 10% sodium hydroxide and again extracted with ether. Since some spontaneous crystallization occurs in the ether, the solvent is removed without drying under vacuum and the residue is recrystallized from 35 ml of ethanol giving 18.0 g of 1-cyclopropylmethyl-5-phenyl-7-chloro-1 H-1,4-benzodiazepine-2(3H)-one, MP 145° to 146°C (65% yield), according to U.S. Patent 3,192,199. 

Benzoyl-6-deoxy-6-iodo-2,3-0-isopropylidene-a-i, - xylohexulofura-nose (47). A solution of 15 grams (31.3 mmole) of 46 in butanone (200 ml.) containing dry sodium iodide (9.3 grams, 62 mmole) was refluxed for 24 hours. The reaction mixture was cooled, the sodium tosylate removed by filtration, and the filtrate concentrated to dryness. The residue was partitioned between water (50 ml.) and chloroform (2 X 50 ml.) the combined chloroform solutions were washed with water, dried over sodium sulfate and concentrated to a colorless sirup which spontaneously crystallized. Recrystallization from aqueous methanol afforded pure material in two crops (11.6 grams, 85%), m.p. 115°-117°C, [ ]D24 + 36.0° (c, 5.3). Anal Calcd. for C16H1906 C, 44.2 H, 4.4 I, 29.3. Found C, 44.3 H, 4.5 I, 29.4. 

Method B (one-pot procedure)-. 5 g (33 mmol) of L-arabinose. 12 mL of ethanol and 4mL (36.7 mmol) of bcnzylaminc arc heated on a steam bath for 5 to 10 min to give a clear solution. After cooling, 2.5 mL of anliyd hydrogen cyanide are added. Spontaneous crystallization of the product begins within a few minutes. After cooling for 2 h with an ice-bath, the product is isolated by filtration and washed with ethanol yield 7.0-7.5g (79-85%) nip 129-131 C after recrystallization from ethanol mp 130-132 C. 

This liquid was hydrolyzed under conditions similar to those employed with d,L-arabitol pentaacetate and yielded a sirup which crystallized spontaneously on standing, or immediately if seeded with ribitol. The crude product melted at 96-104° upon recrystallization from ethanol the melting point and mixed melting point with an authentic sample of ribitol was 101.5-102°. 

Polymers Polyacrylamide and hydrolyzed polyacrylamide were prepared by the American Cyanamid Company specifically for this project, starting with l C labelled monomer. The radioactivity level of the monomer was kept below 0.20 mC /g in order to avoid significant spontaneous polymerization, utilizing a copper inhibitor. The homopolymer was synthesized by free radical solution polymerization in water at 40°C, using monomer recrystallized from chloroform, an ammonium persulfate-sodium metabisulfite catalyst system, and isopropanol as a chain transfer agent. Sodium... 

The synthesis of halcinonide is summarized in Figure 1, starting with 16a-hydroxy-9a-fluorohydrocortisone (A1 -pregnene-9a-fluoro-llg,16a,17a,21-tetrol-3,20-dione dihydrotriamcinolone, I), which is available commercially.10-13 This tetrahydroxy steroid is slurried in acetone, and then 70% perchloric acid is added slowly. The acetonide, II (9a-fluoro-llg, 16a, 17, 21-tetrahydroxypregn-4-ene-3, 20-dione, cyclic 16,17-acetal with acetone dihydrotriamcinolone-acetonide) precipitates spontaneously from solution. Mesyl chloride is added to the acetonide in pyridine to give the 21-mesylate derivative (dihydrotriamcinolone acetonide-21-mesylate, III). Compound III is dissolved in dimethylformamide, lithium chloride is added and the mixture is refluxed to produce halcinonide (IV), which is recrystallized from a solution of ft-propanol in water. 

The dextrose monohydrate obtained today by the foregoing method is a high grade product practically pure chemically. Where higher purity is occasionally desired, this product is recrystallized by essentially the same methods as described earlier.18 The absence of appreciable amounts of impurities renders crystallization somewhat easier. Nevertheless, the tendency for uncontrolled spontaneous crystallization is still encountered so that care is necessary in cooling the mass at the... 

Further variations on the epoxyketone intermediate theme have been reported. In the first (Scheme 9A) [78], limonene oxide was prepared by Sharpless asymmetric epoxidation of commercial (S)-(-)- perillyl alcohol 65 followed by conversion of the alcohol 66 to the crystalline mesylate, recrystallization to remove stereoisomeric impurities, and reduction with LiAlH4 to give (-)-limonene oxide 59. This was converted to the key epoxyketone 60 by phase transfer catalyzed permanganate oxidation. Control of the trisubstituted alkene stereochemistry was achieved by reaction of the ketone with the anion from (4-methyl-3-pentenyl)diphenylphosphine oxide, yielding the isolable erythro adduct 67, and the trisubstituted E-alkene 52a from spontaneous elimination by the threo adduct. Treatment of the erythro adduct with NaH in DMF resulted... 

SYNTHESIS A solution of 0.67 g 5-hydroxyindole (indol-5-ol) in 10 ml dry MeOH was treated with a solution of 0.30 g NaOMe in MeOH, followed by 0.70 g benzyl chloride. The mixture was heated on the steam bath for 0.5 h, and the solvent removed under vacuum. The residue was suspended between H20 and CH2CI2, the organic phase separated and the aqueous phase extracted once with CH2CI2. The combined organics were stripped of solvent under vacuum, and the residue distilled. A colorless fraction came over at 170-190 °C and spontaneously crystallized in the receiver. There was obtained 0.90 g (80%) 5-benzyloxyindole with a mp 81-86 °C which increased, on recrystallization from toluene / hexane, to 94-96 °C. A sample prepared from the decarboxylation of 5-benzyloxyindole-2-carboxylic acid has been reported to have a mp of 102 °C from benzene. 

Although most additives that have been studied retard growth on all faces of the crystal, there are some which definitely promote growth on certain faces. For example, repeated recrystallization of lactose removes growth-promoting trace substances, so that crystal growth is much slower in supersaturated solutions of this lactose than in less purified solutions. The tendency toward spontaneous nucleation is also lowered upon repeated recrystallization. 

To a solution of 13 g 2,5-dimethoxy-4-(n)-propylbenzaldehyde in 100 mL nitromethane, there was added 1.3 g anhydrous ammonium acetate and the mixture held at reflux for 1 h. Removal of the solvent/reactant under vacuum yielded a spontaneously crystallizing mass of orange solids that was removed with the help of a little MeOH. After filtering and air drying there was obtained 7.5 g 2,5-dimethoxy-B-nitro-4-(n)-propylstyrene with a mp of 118-122 °C. Recrystallization from CH3CN gave an analytical sample with a mp 123-124 °C. Anal. (C13Hl7N04) N. 

---