Crystallized from ethanol

In spite of their easy interconversion in solution a and p forms of carbohydrates are capable of independent existence and many have been isolated m pure form as crys talline solids When crystallized from ethanol d glucose yields a d glucopyranose mp 146°C [a]o +112 2° Crystallization from a water-ethanol mixture produces p d glucopyranose mp 148-155°C [aj +18 7° In the solid state the two forms do not mterconvert and are stable indefinitely Their structures have been unambiguously con firmed by X ray crystallography... 

Glipi de. GHpi2ide (l-cyclohexyl-3[ -[2-(5-methylpyra2inecarboxamido)eth5l]phenyl]sulfonyl]urea), mol wt 445.55, forms crystals from ethanol, mp 208—209°C. It is known commercially as Glucotrol. 

Amino-2-hydroxybenZOiC acid. This derivative (18) more commonly known as 4-aminosa1icy1ic acid, forms white crystals from ethanol, melts with effervescence and darkens on exposure to light and air. A reddish-brown crystalline powder is obtained on recrystallization from ethanol —diethyl ether. The compound is soluble ia dilute solutioas of nitric acid and sodium hydroxide, ethanol, and acetone slightly soluble in water and diethyl ether and virtually insoluble in benzene, chloroform or carbon tetrachloride. It is unstable in aqueous solution and decarboxylates to form 3-amiaophenol. Because of the instabihty of the free acid, it is usually prepared as the hydrochloride salt, mp 224 °C (dec), dissociation constant p 3.25. 

A solution of hydrazoic acid (prepared from about 30 g sodium azide) in ca. 200 ml chloroform is prepared in a well-ventilated hood. Cholesterol (15 g) is dissolved in the hydrazoic acid solution and 3.5 ml of triethylamine is added. The reaction mixture is then stirred at room temperature while 7 g of A-chlorosuccinimide is added. The reaction mixture is allowed to stand overnight and then the chloroform solution is washed successively with dilute sodium bisulfite, dilute soldium bicarbonate solutions and finally with water. The chloroform extract is then dried (Na2S04) and the solvent removed in vacuo. The residue is crystallized from ethanol to yield ca. 8.5 g of (101) in colorless needles mp 138-139°. The chloro azide is reduced to the aziridine by lithium aluminum hydride according to the foregoing procedure. 

A total of 222 g of 3)5-acetoxy-5a-pregn-9(l l)-en-20-one-[17a,16a-c]-A -pyrazoline is added portionwise and with stirring during a period of 25 min to 880 ml of diethylene glycol held at 165°. When nitrogen evolution ceases the mixture is cooled to 100° and 3 liters of water is added. The crude product is crystallized from ethanol to yield 146 g (71%) of 3 -acetoxy-16-methyl-5a-pregna-9(ll),16-dien-20-one mp 139-142° [aj 53° (CHCI3) 249 mf.1 (e 8,600). 

The reaction mixture is stirred at 0° for 3 hr and is then allowed to stand at room temperature for 24 hr. The precipitated product is collected by filtration and crystallized from ethanol to give 3-methoxy-D-homo-estra-l,3,5(10)-trien-17a-one (96 1.0 g) mp 138.5-139.5°. Goldberg and Studer report mp 138.5-139.5°." ... 

In spite of theii easy interconversion in solution, a and p fonns of carbohydrates are capable of independent existence, and many have been isolated in pure fonn as crystalline solids. When crystallized from ethanol, D-glucose yields a-D-glucopyianose, mp 146°C, [a]o -1-112.2°. Crystallization from a water-ethanol mixture produces P-d-glucopyranose, mp 148-155°C, +18.7°. In the solid state the two fonns do not... 

To a solution of 112 (2.0 g, 43.0 mmol) in 50 mL of dry THF at -65°C was added a solution of 111 (4.45 g, 34.0 mmol) in 100 mL of absolute ethanol containing 5 mL of acetic acid cooled to - 65°C in one portion. After stirring for 15 min., dry triethylamine (4.8 g, 510 mmol) was added. The reaction continued for 24 h with slow warming to room temperature before reducing the volume to 10 mL. The crude 113 was brought to pH 10 with potassium carbonate. The aqueous solution was continuously extracted with chloroform, dried (K2CO3), evaporated onto neutral alumina, placed on a column of neutral alumina (50 g) and eluted with chloroform. The solvent was evaporated and the residue crystallized from ethanol to yield 113 (2.86 g 55%). The yellow solid had a mp = 72.5-73.8°C. 

A solution of 10 g (0.023 mole) of cholesteryl acetate (mp 112-114°) in ether (50 ml) is mixed with a solution containing 8.4 g (0.046 mole) of monoperphthalic acid (Chapter 17, Section II) in 250 ml of ether. The solution is maintained at reflux for 6 hours, following which the solvent is removed by distillation (steam bath). The residue is dried under vacuum and digested with 250 ml of dry chloroform. Filtration of the mixture gives 6.7 g of phthalic acid (87% recovery). The solvent is evaporated from the filtrate under reduced pressure and the residue is crystallized from 30 ml of methanol, giving 6.0 g (58% yield) of -cholesteryl oxide acetate. Recrystallization affords the pure product, mp 111-112°. Concentration of the filtrate yields 1.55 g (15% yield) of a-cholesteryl oxide acetate which has a mp of 101-103° after crystallization from ethanol. 

Hydrocortisone (25 g) and Bendazac chloride (21 g) are suspended in anhydrous dioxane (250 ml). Pyridine (6 ml) is added and the solution is kept under stirring for 2 hours at room temperature, Pyridine hydrochloride which separates is filtered and the clear dioxane solution is added, under strong stirring, to a solution of sodium bicarbonate (20 g) in distilled water (2,500 ml). The colorless precipitate which is formed is filtered, washed with water and dried on a porous plate. The substance crystallizes from ethanol. Needles. MP 174°-176 t Yield 75%. 

Example 2 65 grams of sodium N-acetyl-p-aminophenol were slurried with 500 grams of dry benzene and 80 grams of acetyl salicoyl chloride added. The mixture was heated under reflux for four hours and filtered hot. The excess benzene was removed under vacuum and the crude acetyl salicyclic acid ester of N-acetyl-p-aminophenol crystallized from ethanol. 

Another route is described in U.S. Patent 3,345,365 A mixture containing 10 grams of orthoanilamide, 10 cc of pyridine and 20 cc of acetic anhydride is heated for 3 hours at 50°-60°C and allowed to stand overnight. The solids obtained are filtered and crystallized from ethanol to yield 10.73 grams of N,N -diacetyl-o-anilamide, MP 199°-200°C. 

The filtrate mentioned above consisted of 3 layers. An oily layer which was present between the aqueous and benzene layers was separated, acidified and extracted with ether. The aqueous layer was likewise separated, acidified and extracted with ether. The extracts were combined, dried and evaporated to yield a heavy gum which was crystallized from ethanol to give an additional 2.5 grams of product which melted at 146°-147 C. The total yield of 2-diphenylacetyl-1,3-indandione was 12.7 grams (37%). 

The reaction mixture is refluxed for 1 hour, then the solvent Is slowly distilled off, the distillation being completed in vacuo. The solid residue so obtained is dissolved in 400 ml of water and washed with ether. The solution is acidified with 10% HCI and the 1,2-diphenyl-3,5-dioxo-4-(3 -methyl-2 -butenyl)-pyrazolidlne which separates is purified by crystallization from ethanol (MP 155°Cto 156°C). 

A sample of this product was crystallized from ethanol to show a melting point of 216°C. 

A Preparation of a-Ethyl-m-Nitrocinnamic Acid This acid is prepared from 100 g of m-nitrobenzaldehyde, 210 g of butyric anhydride and 73 g of sodium butyrate. The crude a-ethyl-m-nitrocinnamic acid is crystallized from ethanol giving about 105 g, MP 140° to 142°C. From the filtrates there may be isolated a small amount of a stereoisomer, which when pure melts at 105° to 106°C. 

A) A mixture of 333 parts of 4-(1 -piperazinyDphenol dihydrobromide, 11.2 parts of acetic acid anhydride, 42 parts of potassium carbonate and 300 parts of 1,4-dioxane is stirred and refluxed for 3 days. The reaction mixture is filtered and the filtrate is evaporated. The solid residue is stirred in water and sodium hydrogen carbonate is added. The whole is stirred for 30 minutes. The precipitated product is filtered off and dissolved in a diluted hydrochloric acid solution. The solution is extracted with trichloromethane. The acid aqueous phase is separated and neutralized with ammonium hydroxide. The product is filtered off and crystallized from ethanol, yielding 5.7 parts of 1 acetyl-4-(4-hydroxyphenyl)piperazine MP 181.3°C. 

Diethyl sodium phthalimidomalonate (Barger and Weichselbaum, Organic Syntheses, 1943, Coll. Vol. II, 3B4) (6.52 g) was dissolved in boiling methyl ethyl ketone (BO ml) and a solution of p-nitrobenzyl chloride (3.44 g 1.0 mol) in the same solvent (20 ml) was added. Sodium iodide (ca 0.5 g) dissolved in hot methyl ethyl ketone (10 ml) was introduced, and produced an immediate precipitation. The mixture was refluxed for 1.5 hours, cooled, filtered, evaporated under vacuum and the residual gum crystallized from ethanol. The di-ethyl-p-nitrobenzyl-phthalimidomalonate formed colorless prisms (B8%), MP 103° to 105°C, sharpening to 104° to 105°C on recrystallizing from ethanol. 

After cooling, distilled water (75 cc) is added. The aqueous phase is decanted. The toluene solution is washed with distilled water (25 cc) and then extracted with N-hydrochloric acid (40 cc). The hydrochloric acid solution is made alkaline to phenolphthalein with sodium hydroxide (d = 1.33). The base which separates is extracted with chloroform (50 cc). The chloroform solution is dried over anhydrous sodium sulfate and then evaporated to dryness. There are obtained 5-[3-(4-/3-hydroxyethylpiperazino)propyll-dibenzazepine (7.95 g),thedi-hydrochloride of which, crystallized from ethanol, melts at about 210°C. 

Preparation of Di-(0-Pheny/-a,a-Dimethylethyl)Urea 3.5 grams of a,a-dimethyl-(3-phenyl-propionamide in 420 cc of water was added to a solution of 87.5 grams of potassium hydroxide and 35 grams of bromine in 350 cc of water. After 2 hours at 60°C, the product was obtained on crystallization from ethanol, melting at 184°C. 

After allowing the mixture to evaporate to dryness, water was added and the sulfonamide filtered, washed with water, and dried in vacuo. The crude product (32.5 grams, 96%) obtained melts at 163.5° to 165°C. One crystallization from ethanol chloroform yielded an analytical sample, MP 164.5 to 166.5°C. 

The mixture of the all trans and mainly 9,10-cis vitamin A acid may be separated by fractional crystallization from ethanol. All trans vitamin A acid has a melting point of 180° to 182°C and 9,10-cis vitamin A acid, which crystallized in the form of pale yellow fine needles collected into clusters, has a melting point of 189° to 190°C. 

To 5 grams of N,N -bis[1-methyi-3-(2,2,6-trimethylcyclohexyl)propyl]-N,N -dimethyl-1,6-hexanediamine dissolved in 100 ml of methanol, at 4°C, were added 100 ml methanol containing 10 grams of methyl chloride. The solution was heated in a closed vessel at 60°C for 15 hours. The colorless solution was concentrated and the resulting white solid crystallized from ethanol-acetonitrile-ether to obtain N,N -bis[1-methyl-3-(2,2,6-trimethylcyclo-hexyOpropyl] -N,N -dimethyl-1,6-hexanediamine bis(methochloride) hemihydrate. 

Yield 230.6 g (quantitative). 7-Acetoxy-6-(2, 3 -dibromopropyl)-4,8-dimethylcoumarin was crystallized from ethanol as colorless prisms, MP 141.5° to 142.5°C. 

Hydrolysis 10 mmol of the phosphate salt are dissolved by swirling with Dowex AG50W-X8 (H ) in 200 mL of water. After filtration, the pH is adjusted to 6.0, acid phosphatase (150 U EC 3.1.3.2) is added and the mixture is incubated at 25 CC until complete conversion, as monitored by TLC (48 h). The solution is desalted by ion exchange, concentrated in vacuo, and the residue is crystallized from ethanol to give colorless crystals of D-sorbosc yield 1.6g (89%). 

A mixture of p-chloroanisole (0.5 mol) and PhLi (0.5 mol, prepared from PhBr and Li in ether) in ether (600 ml) was stirred at ambient temperature for 50 h. A solution of TMSCI (0.5 mol) in ether (50 ml) was added with stirring, which was continued for a further 24 h. The mixture was poured into saturated ammonium chloride solution, the layers were separated, and the ethereal layer was dried. Concentration and fractional distillation gave 4-chloro-2-trimethylsilylanisole, b.p. 84°C/2mmHg. which crystallized in the receiver. Three crystallizations from ethanol gave the pure silane (0.3mol, 60%). m.p. 51-51.5°C. 

SiCL. 57 (1.2 rtiL, 10 mmol) is added slowly by syringe, at 20 °C, to a stirred solution of 4-methoxyacetoplienone (1.5 g, 10 mmol) in 10 mb dry ethanol. After stirring for 6 h the mixture is poured into 20 mb water, extracted with CH2CI2 (2x25 mb), dried (MgS04), filtered, and concentrated. Crystallization from ethanol gives 1.162 g (88%) 1484, m.p. 142 °C [37] (Scheme 9.53). 

Rhodium(III) chloride trihydrate (2 g.) is dissolved in 70 ml. of ethanol (95%) in a 500-ml. round-bottomed flask fitted with gas inlet tube, reflux condenser, and gas exit bubbler. A solution of 12 g. of triphenylphosphine (freshly crystallized from ethanol to remove triphenylphosphine oxide) in 350 ml. of hot ethanol is added and the flask purged with nitrogen. The solution is refluxed for about 2 hours, and the crystalline product which forms is collected from the hot solution on a Buchner funnel or sintered-glass filter. The product is washed with small portions of 50 ml. of anhydrous ether yield 6.25 g. (88% based on Rh). This crystalline product is deep red in color. 

Olesen and Szabo obtained crystals from ethanol and acetone53. They found the crystals to have different solubility, melting point and x-ray diffraction patterns. Since acetone is retained in the crystalline lattice, it was indicated that the forms are pseudopolymorphs. 

Sodium fluoroacetate.1 To methyl fluoroacetate (46-0 g., 0-5 mol.) suspended in water (100 c.c. containing a few drops of phenolphthalein) sodium hydroxide (0-5 mol., 20 g. in 100 c.c. water) is added slowly. The mixture is kept well stirred, and the rate of addition governed by the disappearance of the red coloration. When the addition of sodium hydroxide is complete, a few more drops of M.F.A. are added to render the solution acid. It is then evaporated on the water-bath until crystallization starts, cooled and the solid filtered off. More solid is obtained from the filtrate by the addition of alcohol total yield 45-5g. (91-0 per cent). (Found F, 19-0. Calc, for C2H202FNa F, 19-0 per cent.) This is characterized as p-nitrobenzyl fluoroacetate as follows. p-Nitrobenzyl bromide (0-9 g.), dissolved in alcohol (10 c.c.), is added to a solution of sodium fluoroacetate (0-3 g.) in the minimum amount of water. The mixture is heated under a reflux condenser for 2 hr. and allowed to cool the solid is collected by filtration, and crystallized from ethanol as long needles, m.p. 76°. 

Benzamide (43,51) crystallizes from ethanol in space group Pljc. The main features of the crystal structure (52) (Figure 5) are similar to those found in cinnamide. Hydrogen-bonded cyclic dimers are interlinked along the 5.0-A b axis to form ribbons. The ribbons are stacked along the 5.6-A a axis, in an... 

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