Recrystallizations

In principle, then, small crystals should show a higher solubility in a given solvent than should large ones. A corollary is that a mass of small crystals should eventually recrystallize to a single crystal (see Ostwald ripening. Section IX-4). 

Frequently the recrystallized azobenzeno has m.p. 61°, which is unaffected by recrystallisation from alcohol. Upon distillation from a. 50 ml. distilling flask fitted with a short air condenser, the m.p. is raised to 67-5° and the recovery is about 90 per cent. one recrystallisation from diluted alcohol (as above) then gives perfectly pure azobenzene of m.p. 68-5°. 

Phenylacetic acid. Use 5 0 g. of magnesium, 25 g, (23 ml.) of redistilled benzyl chloride (Section IV,22) and 75 ml. of sodium-dried ether. Allow the reaction mixture to warm to 15° and then decompose it with dilute hydrochloric or sulphuric acid. Filter off the crude acid and recrystallize it from water. The yield of pure phenylacetic acid, m.p. 76-77°, is 11 g. 

It was originally separated from zirconium by repeated recrystallization of the double ammonium or potassium fluorides by von Hevesey and Jantzen. Metallic hafnium was first prepared by van Arkel and deBoer by passing the vapor of the tetraiodide over a heated tungsten filament. Almost all hafnium metal now produced is made by reducing the tetrachloride with magnesium or with sodium (Kroll Process). 

Once the reaction mix has cooled after reflux, 500mL of room temperature dHsO can be added and the whole solution extracted with DCM. The DCM layer is separated and the solvent removed by distillation to give the li-nitropropene as an oil of all things. This oil can then be recrystallized in hot methanol just like the crystalline form was [38]. 

They isolated their products after conversion into the solid semi-carbazone, which included recrystallizations (more losses). This and the fact that they distilled those tiny amounts make me believe that yield will be even higher (at least with the HgCl2 route). 

Phenylpropanolamine. - With catalyst prepared as previously described from 0.5g of palladium chloride and 3g of charcoal, it was possible to reduce two portions of 9.8g of isonitrosopropio-phenone (0.06 mol), dissolved in 150 cc. of absolute alcohol containing 7. Og of hydrogen chloride, to phenylpropanolamine in from 145 - 190 minutes with yields of the isolated chloride from 9.4g to 11. Og, or 84 to 98% of the theoretical. After recrystallization from absolute alcohol the salt melted at 191°. The free base was obtained by treating an aqueous solution of the hydrochloride with alkali on cooling, the liberated amino alcohol solidified and after recrystallization from water melted at 103°."... 

The way the chemist knows that she has methylamine and not ammonium chloride is that she compares the look of the two types of crystals. Ammonium chloride crystals that come from this reaction are white, tiny and fuzzy. The methylamine hydrochloride crystals are longer, more crystalline in nature and are a lot more sparkly. The chemist leaves the methylamine crystals in the Buchner funnel of the vacuum filtration apparatus and returns the filtrate to the distillation set up so it can be reduced one last time to afford a second crop. The combined methylamine hydrochloride filter cake is washed with a little chloroform, scraped into a beaker of hot ethanol and chilled. The methylamine hydrochloride that recrystallizes in the cold ethanol is vacuum filtered to afford clean, happy product (yield=50%). 

Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative bydroboration yielded the dienone with a propanol group in porlactone ring were irons in the product as expected (see p. 275). Treatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(or-naphthyl)ethylamine. This was recrystallized to constant rotation. 

Bromo-2-nitrophenylacetic acid (26 g, 0.10 mol) was dissolved in a mixture of 50% HjSO (400 ml) and ethanol (600 ml) and heated to 90°C. Over a period of 1 h, zinc dust (26.2 g, 0.40 mol) was added. slowly and then heating was continued for 2 h. The excess ethanol was removed by distillation. The solution was cooled and filtered. The filtrate was extracted with EtOAc. The filtered product and extract were combined, washed with 5% NaCOj and brine and then dried (MgSO ). The solvent was removed in vacuo and the residue recrystallized from methanol to give 20.5 g (97% yield) of the oxindole. 

Sodium hydride (9.3 g, 0.22 mol) was washed with petroleum ether and DMSO (200 ml) was added and the mixture was heated to 100°C. A solution of diethyl malonate (35.2 g, 0.22mol) in DMSO (50 ml) was then added and stirred for 10 min to give a clear solution. A solution of 4-bromo-3-nitrobenzophenone (30.6 g, 0.10 mol) in DMSO (100 ml) was added and the resulting dark solution kept at 100 C for 1 h. The solution was poured into water (3 1) and extracted (2x) with ether. The extract was washed with water, dried (NajSOj and concentrated in vacuo to give an oil which crystallized. The solid was recrystallized from isopropyl alcohol to give 35.4 g (92% yield) of the product. 

A stirred solution of o-methylpivalanilide (50 mmol) in dry THE (100 ml) was maintained at 15°C under a nitrogen atmosphere. A 1.5 M solution of n-butyllithium in hexane (3 equiv.) was added dropwise. The solution was then maintained at room temperature for 16h. The solution was cooled in an ice-bath and treated with 2 N HCl (60 ml). The organic layer was separated and the aqueous layer was further extracted with benzene. The combined layers were dried (MgS04). The product was obtained in 87% yield and recrystallized from ether-cyclohexane. 

The cinnamate ester prepared as above (23.2 g. 79 mmol) was added as a solid slowly to refluxing xylene (500 ml) over a period of 3 h at a rate that prevented accumulation of unreacted azidocinnamate in the solution (monitored by gas evolution through a gas bubbler). The solution was refluxed for an additional 2 h after gas evolution ceased. The reaction mixture was cooled and the solvent removed in vacuo. The residue was recrystallized from methanol to give pure product (20.7 g, 99% yield). 

Phenyl-3-oxopropanoic acid (25 mmol) and EtjN (87.5 mmol) were dissolved in THF (150 ml) and cooled to —40°C. Ethyl chloroformate (27.5 mmol) was added dropwise to this solution and then the reaction mixture was stirred for 30 min at —20°C. Di-n-hexylamine (27.5 mmol) was added to the suspension and it was stirred at room temperature for an additional hour. The reaction mixture was diluted with water (100 ml) and extracted with ether (400 ml). The extract was washed with aq. 5% HCl (100 ml) and brine (2 X 100 ml) and dried over NajSO. The crude amide was obtained by removal of the solvent in vacuo and phenylhydrazine (25 mmol) was added. The mixture was heated to 100°C for 30 min. The residue was held in vacuo to remove the water formed and then powdered ZnCl2 (125 mmol) was added. The mixture was heated at 170"C with manual stirring for 5 min. The cooled residue was dissolved in acetone (100 ml) and diluted with ether (500 ml). Water (100 ml) was added. The organic layer was separated and washed successively with 5% aq. HCl (100 ml) and brine (2 x 100 ml) and dried over NajSO. The solvent was removed in vacuo, and the residue was recrystallized from EtOAc-hexane. The yield was 79%. 

The hydrazone prepared above (153 g. 0.42 mol) was heated at reflux for 5 h in 5% H2SO4 (750ml). The solution was cooled to 4 "C and after 12h the precipitate was collected by filtration. Recrystallization from MeOH/water (70 30) gave the product (145 g, 99%). 

The above intermediate (8 g, 0.03 mol) in THF (80 ml) was stirred with Raney nickel (40g) for 2h and then carefully filtered. [CAUTION Raney nickel can ignite during filtrationf Cone. HCl (2 drops) was added to the filtrate and it was evaporated in vacuo. Recrystallization of the residue from 2-propanol gave the product (6,0 g) in 89% yield. 

A solution of 2,3-dibromo-5-methoxyaniline (32 g, 0.17 mol) in CHjClj (300 ml) was stirred and cooled in an icc bath. Boron trichloride (1 M in CH2CI2, 180 ml, 0.18 mol), chloroacetonitrile (14.3 g, 0.19 mol) and TiC (1 M in CH CIj, 190ml, 0.19 mol) were added. The resulting mixture was refluxed for 1.5 h. The solution was cooled to room temperature and poured carefully on to a mixture of icc and 20% aq. HCl (700 ml). The organic layer was separated and the CH Clj removed by distillation. The residue was heated to 90°C on a water bath for 30 min. The solution was cooled and the solid collected by filtration. It was partitioned between ether (1.41) and 1 N NaOH (500 ml). The ether layer was washed with brine, dried over Na2S04 and evaporated. The residue was recrystallized from ethanol to give 2-amino-3,4-dibromo-6-methoxy-a-chloroacetophenone (55 g) in 90% yield. 

The above product (24 g, 0.067 mol) was dissolved in 90 10 dioxane-water (300 ml) and sodium borohydride (92.5 g, 0.067 mol) was added. The mixture was refluxed for 4h. The cooled solution was poured into 0.1 N HCl (1.11). A solid precipitated and was collected by filtration, dried and recrystallized from ether hexane to give 6,7-dibromo-4-methoxyindole (18.5 g, 90%). 

Phenylmagnesium bromide (2.8 mol) was prepared in anhydrous ether (21) from bromobenzene (440 g, 2.9 mol) and magnesium turnings (68.0 g 2.8 g-atom). To this solution was added dropwise a solution of indole (328 g, 2.8 mol) in benzene (8(X)ml). The resulting solution was stirred for 10 min and then a solution of cyclopentanoyl chloride (322 g, 2.4 mol) in benzene (800 ml) was added dropwise. The solution was stirred for 1 h and then water (11) was added carefully. The precipitate which formed was collected by filtration and dried to give 169 g of crude product. Additional product (97 g) was obtained by evaporation of the organic layer of the filtrate. The combined products were recrystallized from toluene to give 250 g (49% yield) of pure product. 

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