Crude Crystallization

You know how just a couple of paragraphs ago where the chemist first filtered the crude crystals from the chilled reaction mixture, then washed them with water or acetic acid Well, all that liquid filtrate has a lot of valuable, unreacted piperonal or benzaldehyde in it. To rescue the stuff the chemist dilutes the mixture with 500ml dHaO and extracts it with DCM. The DCM is washed with 100ml 5% NaOH solution then vacuum distilled to give a dark oil which is unreacted aldehyde. Hey That s a lot of good material that can be put through the process again. 

Fig. 3. Typical nitric acid oxidation process. A, reactor B, optional cleanup reactor C, bleacher D, NO absorber E, concentrating stUl F, crude crystallizer G, centrifuge or filter H, refined crystallizer I, centrifuge or filter , dryer K, purge evaporator L, purge crystallizer M, centrifuge or filter N,...

A mixture of 2.0 g (0.064 mol) of 2-fluoromethyl-3-(o-tolyl)-6-nitro-4(3H)-qulnazolinone, Oi g of 5% palladium-carbon and 100 ml of acetic acid is shaken for 30 minutes in hydrogen gas. The initial pressure of hydrogen gas is adjusted to 46 lb and the mixture is heated with an infrared lamp during the reaction. After 30 minutes of this reaction, the pressure of hydrogen gas decreases to 6 lb. After the mixture is cooled, the mixture is filtered to remove the catalyst. The filtrate is evaporated to remove acetic acid, and the residue is dissolved in chloroform. The chloroform solution is washed with 5% aqueous sodium hydroxide and water, successively. Then, the solution is dried and evaporated to remove solvent. The oily residue thus obtained is dissolved in 2 ml of chloroform, and the chloroform solution is passed through a column of 200 g of silica gel. The silica gel column is eluted with ethyl acetate-benzene (1 1). Then, the eluate is evaporated to remove solvent. The crude crystal obtained is washed with isopropylether and recrystallized from isopropanol. 0.95 g of 2-fluoromethyl-3-(o-tolyl)-6-amino-4(3H)-quinazolinone Is obtained. Yield 52.5% MP 195°-196°C. 

The inosine-containing solution, which was obtained by separating the cells from the resulting fermentation liquid, was treated with both decolorizing resins and anion exchange resins by means of a conventional method and then acetone was added to crystallize the inosine. 1.47 g of the crude crystals of inosine were obtained from 3.5 liters of the culture liquid containing 1 g of inosine per liter. 

To a Soiution of 3.0 g of 16/3-ethylestra-4-ene-3,17-dione dissoived in 150 ml of dioxane, are added 15 g of ethyl orthoformate and 0.1 g of p-toluenesuifonic acid, followed by stirring for 2 hours at room temperature. The reaction solution is poured into 300 ml of a 5% aqueous solution of Sodium hydrogen carbonate and the resultant mixture is extracted with ether. The ether layer is washed with water and dried, followed by evaporation of the solvent to give Crude crystals of 3-ethoxy-18/3-ethylestra-3,5-diene-17-one. The crystals are recrystallized from ether to give 30 g of the compound melting at 114°C to 115°C. 

Crude crystals of 3-(2-methylthio-2-piperidinoacetyl -5-phenylisoxazole (1.631 g) are suspended in 20 ml of methanol without being further purified and the suspension is stirred after a portionwise addition (in about 10 minutes) of 143 mg (3.7B mmol) of sodium borohydride at room temperature for about 30 minutes. 

Miyamoto (100) extracted and obtained crude crystals of a germination inhibitor from the bark of Syringa vulgaris (lilac). 

A suspension of tetraphenylphosphonium iodide (2.0 g, 0.0043 mol) in anhydrous ether (5 ml) was combined with a 1 N solution of phenyl lithium (5 ml, 0.005 mol). The reaction mixture was allowed to stand for 8 days, after which the dark red supernatant solution was decanted. (In addition to the lithium salts, it still contained 10% phenyl lithium.) The residue was washed with anhydrous ether under nitrogen. Thereby was precipitated the pentaphe-nylphosphorane as crude crystals. The supernatant turbid suspension was discarded. This purification procedure was repeated until the supernatant ether remained clear. The thus isolated product was recrystallized from cyclohexane under nitrogen to yield the pure pentaphenylphosphorane (1.79 g, 60%) of melting point (mp) 124°C. 

Precipitate with aq. ammonia. Evaporate the soln. down to about 100 c.c., and filter the ot liquid so as to remove calcium sulphate. The cone. soln. is sat. with ammonium alum and allowed to stand for some time. The mixed crystals of potassium, rubidium, and oeesium alums and of lithium salt are dissolved in 100 c.c. of distilled water and recrystal-lized. The recrystallization is repeated until the crystals show no spectroscopic reaction for potassium or lithium. The yield naturally depends on the variety of lepidolite employed. 100. grms of an average sample gives about 10 grms. of crude crystals and about 3 grms. of the purified caesium and rubidium alums. For the purification of caesium and rubidium salts, see the chlorides. The mother-liquors are treated with an excess of barium carbonate, boiled, and filtered. The filtrate is acidified with hydrochloric acid, and evaporated to dryness. The residue is extracted with absolute alcohol in which lithium chloride is soluble, and the other alkali chlorides are sparingly soluble. 

Filter the solution through a folded filter and set it aside in a quiet place to crystallize. The crystals are glassy in appearance and should not be too large or grown together. Drain them on a Witte plate and evaporate the mother liquor for a second crop. They may be obtained as needles as lath-shaped crystals or in a compact, many-sided form. The last named is the most desirable form, and conditions should be varied to avoid supersaturation (Exercise 6) until such crystals are obtained. Meanwhile, prepare some effloresced sodium sulfate by gently warming about 100 g. of the crude crystals until they fall into white powder. Place this powder in the bottom of an empty desiccator and... 

To prepare the corresponding chloride, the crude crystals from the oxidation are dissolved in hot water (slightly acidified with acetic add) allowing 400ml of water for each 20g of solid. This solution is then treated with 40g of ammonium chloride and cooled immediately. Hie salt is isolated as described previously. 

When all the chlorine has been added, the flask and contents (Note 2) are cooled to —78° and held at this temperature for 30 minutes. The white crystalline product which separates is collected on a sintered-glass funnel, 160-170 g. (45-48%) of crude crystals, m p 53-55°, is obtained. The crude product when... 

H2 gas was bubbled through a soln of EtMe2COC(0)-Pro-Pro-OBzl in the presence of Pd for several hours. The solvent was removed by concentration and the residual product purified by washing with EtOAc and 5% NaHC03. Crude crystals were obtained by acidifying the 5% NaHC03 soln of the product with 6 M HC1. The product was recrystallized (hexanes) yield was not reported. 

To ail equivalent mixture of resorcinol la (1.1 g, 10.0 mmol) and ethyl acetoace-tate 2a (1.3 g, 10.0 mmol) was added TsOH (0.3 g, 1.5 mmol) in a mortar and ground well with a pestle at room temperature. The mixture was heated at 60 °C for 10 min under atmosphere. After cooling, water was added to the reaction mixture and the crystalline products were collected by filtration to give 7-hydro-xy-4-methylcoumarin 3a (1.73 g) in 98% yield. The crude crystals thus obtained were recrystallized from EtOH to give pure 3a as colorless prisms (mp 185-187 °C). 

A suspension of the powdered 1 1 inclusion compound of (-)-l and 2a (3.21 g) in water (120 mL) containing sodium alkylsulfate as a surfactant was irradiated for 12 h while being stirred at room temperature. The reaction mixture was filtered to give crude crystals and an aqueous solution. The crude crystals were purified by column chromatography on silica gel followed by recrystallization from AcOEt to give (+)-3a of 98% ee (0.42 g, 59% yield) and recovered (-)-l (0.24 g, 25% yield). 

When a solution of 3 and two molar equivalents of rac-26a in ether-light petroleum was kept at room temperature for 12 h, a crystalline 1 1 inclusion complex of 3 and (+)-26a was obtained. Two recrystallizations of the crude crystals from ether-light petroleum gave pure crystals which upon distillation in vacuo gave (+)-26a of 55% ee. Decomposition of (+)-26a with hydrazine gave (+)-27a of 55% ee in 40% yield. By the same procedure, (-)-27b of 30% ee, (+)-27c of 30% ee, and (-)-27d (ee was not determined) were obtained.15... 

Purification of the product 330.5 mg of crude crystals were dissolved in a mixed solvent of 50 vol. parts of cyclohexane and 10 vol. parts of ethyl acetate. The solution was slowly passed through a column filling 40 g of silica gel and the product was gradually separated to obtain 188.2 mg (yield 62.86%) of pure product. It was confirmed that the product was 3-hydroxy-... 

The residue was subjected to azeotropic operation with toluene two times, and ether was added to the residue. The precipitate derived from trioxane was removed by filtration and washed with ether, and the combined ethereal solutions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with water and aqueous saturated solution of sodium chloride, was dried, and was concentrated to give 4 g of an oily material. The oily material was dissolved in 20 ml of methanol and to the solution was added 20 ml of aqueous 1 N solution of sodium hydroxide, and the mixture was stirred for 14 hours at room temperature. After removal of methanol under reduced pressure, water was added to the mixture, and this solution was acidified to pH 3 with aqueous 2 N hydrochloric acid. The mixture was extracted five times with ethyl acetate, and the ethyl acetate extract was dried and concentrated to give 3.5 g of crude crystals. After addition of ethanol to the crude crystals, the crude crystals were filtered. The filtrate was concentrated, and to the residue was added ethanol and ethyl acetate, and precipitate was collected by filtration. The combined amount of the crude crystals was 1.6 g. After the combined crude crystals were methylated with diazomethane, the reaction product was dissolved in 20 ml of ethyl acetate. To this solution was added 1.5 g of sodium acetate and 300 mg of 10% palladium-carbon, and the mixture was stirred for 2 hours under hydrogen. Then, the reaction product was filtered, and after addition of aqueous saturated solution of sodium hydrogen carbonate to the filtrate, the mixture was extracted two times with ethyl acetate. The extract was washed with an aqueous saturated solution of sodium chloride, dried, and concentrated to give 1.3 g of crude crystals. The crude crystals were recrystallized from ethyl acetate to yield 765 mg of the title compound (melting point 134-135°C, yield 43%). 

To a suspension of 1 g of lithium aluminum hydride in 10 ml of anhydrous tetrahydrofuran cooled in an ice bath was added dropwise a solution of 1.94 g of methyl 3-methyl-trans-4a-cisoid-4a,5a-cis-5a-l,4a,5,5a,10b,10c-hexahydro-7-dioxino[5,4-a]cyclopenta[b]benzofurancarboxylate in 40 ml of anhydrous tetrahydrofuran. After being stirred for 30 min at room temperature, the reaction mixture was cooled in an ice bath. The excess of lithium aluminum hydride was decomposed by the addition of ethyl acetate, and aqueous saturated solution of potassium sodium tartarate was added to the reaction mixture. After filtration of the mixture, the filtrate was concentrated and the residue was dissolved in 10 ml of methanol. After addition of 2 g of potassium carbonate to the solution, the mixture was stirred for 3 hours at room temperature and was concentrated. After water was added to the residue, the aqueous mixture was extracted 3 times with ethyl acetate. The combined organic layers were washed with water and saturated aqueous solution of sodium chloride, dried, and concentrated to give 2 g of crude crystals. The crude crystals were recrystallized from ethyl acetate-hexane to yield 1.49 g of the pure crystals of the titled compound (m.p. 124-125°C, yield 85%). 

Methyl-l-piperazinyl)benzimididazole (5.00 g) prepared as above is dissolved in N,N-dimethylformamide (50 ml) and thereto is added sodium hydride (concentration 50%) (1.50 g) at room temperature, and the mixture is stirred for 30 minutes. To the mixture is added 2-bromoethyl ethyl ether (4.00 g), and the mixture is stirred at 70°C for 10 hours. To the reaction mixture is added water (150 ml), and the mixture is extracted with ethyl acetate. The extract is washed with water, dried over anhydrous magnesium sulfate and then concentrated to give a brown oily substance (5.40 g). The brown oily substance is treated with fumaric acid (3.26 g) in hot ethanol. The crude crystals thus obtained are recrystallized from ethyl acetate-ethanol to give l-[2-(ethoxy)ethyl]-2-(4-methyl-l-piperazinyl)benzimidazole 3/2 fumarate (6.31 g) as colorless plates, melting point 167.5°-168.5°C. Elementary analysis for C22H30N4O7 Calcd. (%) C, 57.13 H, 6.54 N, 12.11 Found (%) C, 57.04 H, 6.44 N, 12.02. 

After removal of such tar or gum, the concentrate is further evaporated at a temperature below about 50°C to about one-fourth the volume, i.e., 70 gallons is concentrated to about 15 to 20 gallons. This concentrate is cooled to a temperature of about 0°C to 5°C and allowed to stand for an extended period, such as overnight, whereupon there is a separation of crude crystalline glaucarubin therefrom. The crude crystals thus formed are removed by filtration and the mother liquors again concentrated to about one-half volume and cooled to permit separation of a second batch of crude glaucarubin crystals. The two batches of crude glaucarubin crystals are combined and dried preparatory to further purification. 

A solution of 642 mg of thioacetic acid in 14 ml of dried dimethylformamide was added to a suspension of 374 mg of 50% sodium hydride in 13 ml of dried dimethylformamide in a nitrogen stream, followed by stirring at room temperature for 25 minutes. To the mixture were added 975 mg of sodium iodide and then a solution of 2.52 g of trans-l-(p-nitrobenzyloxycarbonyl)-4-methanesulfonyloxy-L-prolineamide in 12 ml of dried dimethylformamide, and the resulting mixture was heated to 70°C for 6 hours while stirring. The reaction mixture was poured into a cool aqueous solution of sodium chloride and extracted with benzene. The extract was washed successively with a 10% aqueous solution of sodium sulfate and a sodium chloride aqueous solution, dried over sodium sulfate and distilled off to remove the solvent. The resulting crude crystals were washed with a warm mixed solvent of tetrahydrofuran and benzene to obtain (2S,4S)-l-(p-nitrobenzyloxycarbonyl)- 2-carbamoyl-4-acetylthio-L-prolineamide. Melting point 168.5-169.5°C. 

Cone, sulfuric acid (11 ml) was added to 4-(N,N-dimethylamino)-2-phenyl-2-(2-pyridyl)-valeronitrile (6.3 g) at 0°C. Then water (1 ml) was added thereto. After being heated at 90°C for 3 hours, the mixture was poured into ice-water, adjusted to pH 10 with 10% aqueous sodium hydroxide and extracted with ethyl acetate (3x50ml). The extracts were combined, and washed with water, dried over magnesium sulfate and evaporated under reduced pressure. The obtained crude crystal was recrystallized from diethyl ether to give 4-(N,N-dimethylamino)-2-phenyl-2-(2-pyridyl)-valeramide (1.89 g). MP 132-134°C. 

The mother liquor from the crude crystals is evaporated to dryness on the water bath and the residue extracted with 6 ml. of alcohol. The alcoholic extract in turn is evaporated to dryness and washed three times with 4 ml. of anhydrous ether. The additional yield thus obtained is 1.8 g., while the total yield is 3.67 g. (63%). Anal. Calcd. for [Co(C6H5C2N5H6) 3]C13-2.5H20 N, 28.32 Cl, 14.36 Co, 7.96. Found N, 28.13 Cl, 14.40 Co, 7.98. 

When all the bromine has been added, the flask is cooled in ice-water and the product filtered with suction. The crude crystals are washed with 50 per cent ethyl alcohol until colorless (about 100 cc. is required). The material so obtained, when air-dried, melts at 106-108° and weighs 55-60 g. It is recrystallized from 400 cc. of 95 per cent ethyl alcohol, from which it separates as colorless needles melting at 108-109 °. The yield (Note 1) is 48-50 g. (69-72 per cent of the theoretical amount). 

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