Triturating

Place 1 0 g. of the monobasic acid and 2 g. of aniline or p-toluidine in a dry test-tube, attach a short air condenser and heat the mixture in an oil bath at 140-160° for 2 hours do not reflux too vigorously an acid that boils below this temperature range and only allow steam to escape from the top of the condenser. For a sodium salt, use the proportions of 1 g. of salt to 1 5 g. of the base. If the acid is dibasic, employ double the quantity of amine and a reaction temperature of 180-200° incidentally, the procedure is recommended for dibasic acids since the latter frequently give anhydrides with thionyl chloride. Powder the cold reaction mixture, triturate it with 20-30 ml. of 10 per cent, hydrochloric acid, and recrystallise from dilute alcohol. 

Triturate 20 g. of dry o-toluidine hydrochloride and 35 5 g. of powdered iodine in a mortar and then grind in 17 -5 g. of precipitated calcium carbonate. Transfer the mixture to a conical flask, and add 100 ml. of distilled water with vigorous shaking of the flask. Allow the mixture to stand for 45 minutes with occasional agitation, then heat gradually to 60-70° for 5 minutes, and cool. Transfer the contents of the flask to a separatory funnel, extract the base with three 80 ml. portions of ether, diy the extract with anhydrous calcium chloride or magnesium sulphate, and remove the excess of solvent. The crude 5-iodo-2-aminotoluene separates in dark crystals. The yield is 32 g. Recrystallise from 50 per cent, alcohol nearly white crystals, m.p. 87°, are obtained. 

A solution of 2-aminobenzophenone (98 g, 0.50 mol) and methyl 2-(methyl-thio)propanoate (74 g, 0,50 mol) in CH Clj (21) was cooled to —70 C and 95% 7-butyl hypochlorite (56 g, 0.5 mol) was added dropwise at such a rate that the temperature did not rise above — 65 C. One hour after the addition was complete, EtjN was added and the mixture was allowed to come to room temperature. The solution w as mixed with 3 N HCl (800 ml) and stirred for 1 h. The organic layer was separated, dried (Na2S04 ) and filtered. The solution was evaporated in vacuo and the residue triturated with ether. Filtration gave the 3-(methylthio)oxindole intermediate (92 g) in 62% yield. 

Cochineal (indicator) triturate 1 g with 75 mL alcohol and 75 mL water, let stand for two days and filter pH range red 4.8-6.2 violet. 

Also reported as commercial products are selenium amino acid chelate, selenium ascorbate, selenium aspartate, and selenium citrate triturations, as well as selenium dibromide, selenium dichloride, selenium lysinate, and selenium sulfide bentonite. 

The biotin market is divided between agricultural and human use, with —90% of biotin used in the animal health care market and —10% for the human nutritional market. The major producers of biotin are Hoffmann-La Roche, Lon2a, E. Merck-Darmstadt, Rhc ne-Poulenc, Sumitomo Pharmaceutical, E. Sung, and Tanabe Seiyaku (100). Worldwide production of biotin in 1994 was approximately 60 metric tons. The Hst price for pure biotin in 1995 was — 7.00/g whereas, the Hst price for technical feed-grade biotin was — 5.50/g. Biotin is used in various pharmaceutical, food, and special dietary products, including multivitamin preparations in Hquid, tablet, capsule, or powder forms. One of the commercially available products of i7-biotin is Britrit-1, which is a 1% biotin trituration used in food premixes. 

In the human market, oral and parenteral dosage forms are prepared from the crystal. However, because of the extremely high potency, more dilute (0.1—10%) forms are avabable. These include dilutions with mannitol, triturations on dicalcium phosphate or resins, and spray-dried forms. Prices for these forms are driven by that of the crystal, which in early 1996 was ca 9.50/gram (95). Prices for the vitamin have risen during the first half of the 1990s. However, Htde growth in price beyond inflation is anticipated. 

Copper(II) sulfate monohydrate [10257-54-2] CuS04-H2 0, which is almost white in color, is hygroscopic and packaging must contain moisture barriers. This product is produced by dehydration of the pentahydrate at 120—150°C. Trituration of stoichiometric quantities of copper(II) oxide and sulfuric acid can be used to prepare a material of limited purity. The advantages of the monohydrate as opposed to the pentahydrate are lowered freight cost and quickness of solubilization. However, these advantages are offset by the dustiness of the product and probably less than one percent of copper sulfate is used in the monohydrate form. 

A solution of 7-chloro-2.3-dlhydro-1-acetyl-S-phenyl-1H-1,4-benzodlazepine-4-oxlde 1 (7 0 g, 22 mmol) in AC20 (60 mL) was relKjxed lor 7 h. The solvent was removed m vacuum arxl the residue was triturated with EtaO. The crystalline product after recrystaillzation from hexane CH2CI2 gave 4.6 g ol 2 (59%), irp ITT-ITg-C. 

Phenylpftenanttirldlne (3).3 Amine hydrochloride 1 (2.72 g, 9 28 mmol) in EtOH (75 mL) was treated with 0 926 N cold solution of KCXI. Colorless crystals appear The mixture was shaken lor 30 mtn in ice, water was added and the product was filtered and dryed (PaOs) to afford 2.7 g of 2 (100%), rnp 102°C (hexane) 2 (2 0 g, 6 6 mmol) in anh pyndine (20 mL) was treated with an excess of NaOCHa (exothermc) Alter 20 h the solvent was removed In vacuum, the residua triturated with EtaO and the extract treated with dry HCI to obtain the hydrochlonda of 3, mp 107-108°C (from petroleum ether), mp 95-100° (Irom water) Olphenylmethyieneanlllna (5). To a suspension of lead tetraacetate (4.9 g, fO mmol) in PhH (100 mL) under Na was added a solution of tnphenyhnethylamine 4 (2 6 g, 10 mmol) in PhH (100 mL) dropwise under stirring The mixture was refluxed for 1 h, cooled, filtered, washed and the solvent evaporated The residue was crystallized from EtOH to give 2 2 g of 5 (85%), mp 111-112°C. 

The solution is immediately separated from the insoluble material by filtration on a 20-cin. Buchner funnel, and the cake is sucked as dry as possible. The residue is transferred to the 3-1. beaker, triturated well with 1 1. of water, and then separated from the liquid by filtration. In the same manner, the residue... 

To the white residue (Note 1) are added 25 g. of 98-100% formic acid and 2-3 drops of concentrated nitric acid. The mixture is heated for 24 hours on a steam bath. The resulting syrup is dissolved in 100 ml. of water and, with the temperature at 50°, is carefully treated with 25 g. of anhydrous sodium carbonate. The solution is then placed in an evaporating dish and evaporated to dryness on the steam bath. The residue is extracted twice by boiling it with 200-ml. portions of absolute ethanol, and the alcohol solutions are filtered. The alcohol is removed by evaporation and the residue triturated with 100 ml. of a mixture of equal... 

Amides are stable compounds. The lower-melting members (such as acetamide) can be readily purified by fractional distillation. Most amides are solids which have low solubilities in water. They can be recrystallised from large quantities of water, ethanol, ethanol/ether, aqueous ethanol, chloroform/toluene, chloroform or acetic acid. The likely impurities are the parent acids or the alkyl esters from which they have been made. The former can be removed by thorough washing with aqueous ammonia followed by recrystallisation, whereas elimination of the latter is by trituration or recrystallisation from an organic solvent. Amides can be freed from solvent or water by drying below their melting points. These purifications can also be used for sulfonamides and acid hydrazides. 

Chlorophenyl isothiocyanate [2131-55-7] M 169.6, m 44 , 43-45 , 45 , 46 , 47 , b 110-115 /4mm, 135-136 /24mm. Check the IR first. Triturate with pet ether (b 30-60°) and decant the solvent. Repeat 5 times. The combined extracts are evap under reduced press to give almost pure compound as a readily crystallisable oil with a pleasant anise odour. It can be recrystd from the minimum vol of EtOH at 50° (do not boil too long in case it reacts). It can be purified by vac distn. IRRITANT. [Org Synth Coll Vol V 223 7 975.1... 

Crystd from pyridine (30mL/g), washed with pyridine, then triturated with water (25mL7g), adjusting to pH 5 by adding M HCl. Recrystd by heating, then cooling, the soln. Filtered, washed with water and dried at 110°. Has also been crystd from water (charcoal). 

The material is triturated with saturated sodium bisulfite solution (2 cc. per gram), and after about three hours the pasty mixture is filtered with suction. The addition product is washed with absolute alcohol and then with ether and transferred to a flask fitted for steam distillation. Excess sodium carbonate solution is added and the aldehyde is distilled in a current of steam. 

Careful stirring and trituration are necessary to ensure the complete decomposition of every drop of the yellow paste. 

Toluene is a useful co-solvent in metal-ammonia reductions as first reported by Chapman and his colleagues. The author has found that a toluene-tetrahydrofuran-ammonia mixture (1 1 2) is a particularly useful medium for various metal-ammonia reductions. Procedure 8a (section V) describes the reduction of 17-ethyl-19-nortestosterone in such a system. Ethylene dibromide is used to quench excess lithium. Trituration of the total crude reduction product with methanol affords an 85% yield of 4,5a-dihydro-17-ethyl-19-nortestosterone, mp 207-213° (after sintering at 198°), reported mp 212-213°. For the same reduction using Procedure 5 (section V), Bowers et al obtained a 60% yield of crude product, mp, 196-199°, after column chromatography of the total reduction product. A similar reduction of 17-ethynyl-19-nortestosterone is described in Procedure 8b (section V). The steroid concentration in the toluene-tetrahydrofuran-ammonia system is 0.05 M whereas in the ether-dioxane-ammonia system it is 0.029 M. 

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