Solid-liquid filtration hydroxide

A(A -Bis(3-aminopiopyl)ethylenediamme is prepared by the method of E. K. Barefield. Six moles of 1,3-propanediamine is dissolved in 1.4 L of absolute ethanol and the solution is cooled to 5° in an ice bath. To this solution is added 0.75 mole of 1,2-di-bromoethane from a dropping funnel with vigorous stirring. After the addition is complete, the reaction is heated to reflux temperature for I A hours.. Potassium hydroxide, 150 g, is added and the mixture is refluxed for a further 1 hour. The reaction mixture is cooled to room temperature and filtered to remove the solids. The filtrate is evaporated to a sludge on a rotary evaporator and the semisolid is extracted several times with diethyl ether. The ether solution is evaporated until a viscous liquid remains. The liquid is distilled in vacuo (b.p. 138-148°/2 ton) and stored over potassium hydroxide pellets in a bottle protected from light. The yield is 64 g. 

In a 1-litre three-necked flask, fitted with a mechanical stirrer, reflux condenser and a thermometer, place 200 g. of iodoform and half of a sodium arsenite solution, prepared from 54-5 g. of A.R. arsenious oxide, 107 g. of A.R. sodium hydroxide and 520 ml. of water. Start the stirrer and heat the flask until the thermometer reads 60-65° maintain the mixture at this temperature during the whole reaction (1). Run in the remainder of the sodium arsenite solution during the course of 15 minutes, and keep the reaction mixture at 60-65° for 1 hour in order to complete the reaction. AUow to cool to about 40-45° (2) and filter with suction from the small amount of solid impurities. Separate the lower layer from the filtrate, dry it with anhydrous calcium chloride, and distil the crude methylene iodide (131 g. this crude product is satisfactory for most purposes) under diminished pressure. Practically all passes over as a light straw-coloured (sometimes brown) liquid at 80°/25 mm. it melts at 6°. Some of the colour may be removed by shaking with silver powder. The small dark residue in the flask solidifies on cooling. 

B. Tropohne. In a 1-1., three-necked, round-bottomed flask equipped with a mechanical stirrer, addition funnel, and reflux condenser are placed 500 ml. of glacial acetic acid and then, cautiously, 100 g. of sodium hydroxide pellets. After the pellets have dissolved, 100 g. of 7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one is added and the solution is maintained at reflux under nitrogen for 8 hours. Concentrated hydrochloric acid is then added until the mixture is about pH 1 approximately 125 ml. of acid is required. After the addition of 1 1. of benzene, the mixture is filtered and the solid sodium chloride is washed with three 100-ml. portions of benzene. The two phases of the filtrate are separated and the aqueous phase is transferred to a 1-1. continuous extractor (Note 8) which is stirred magnetically. The combined benzene phase is transferred to a 2-1. pot connected to the extractor and the aqueous phase is extracted for 13 hours. Following distillation of the benzene, the remaining orange liquid is distilled under reduced pressure... 

A suspension of 40 g 3-acetylaminomethyl-5-amino-2,4,6-triodobenzoic acid in 180 ml acetic anhydride were mixed with 0.4 ml concentrated sulfuric acid. An exothermic reaction was thereby initiated. Acetylation was completed by heating to 80°C for three hours. The reaction mixture was then evaporated to dryness in a vacuum at a temperature not exceeding 50°C. The residue was treated with a mixture of 30 ml concentrated aqueous ammonium hydroxide and 40 ml water, whereby the solid material dissolved with spontaneous heating. Within a few minutes, the ammonium salt of the acetylated product started precipitating. The precipitate and residual liquid were cooled externally with ice after about 15 minutes. The salt was separated from the liquid by filtration with suction, and was washed with ice cold saturated ammonium chloride solution. 

At the end of the incubation period the fermentation culture mixture is adjusted to pH 2 with concentrated hydrochloric acid, the solid material present is removed by filtration, and the filter cake is washed with water. The washings are combined with the main filtrate, adjusted to pH 7.0, and 15.5 liters of the filtered culture liquid is introduced into a columnar exchanger d /a" i.d.) packed with 380 ml of carboxylic acid resin which has been preliminarily washed in succession with two liters of an aqueous solution of 37.5 grams of sodium hydroxide and with two liters of water. The column containing paromomycin is washed with two hold-up volumes of water and is eluted with 0.5 N hydrochloric acid. 

To a mixture of 50 g (0.4 mol) of nitrobenzene, 180 ml of 30% sodium hydroxide, 20 ml of water and 50 ml of ethanol, 100-125g (1.5-1.9g-atom) of zinc dust is added portionwise with efficient mechanical stirring until the red liquid turns light yellow. After stirring for an additional 15 minutes, 1 liter of cold water is added, the mixture is filtered with suction, the solids on the filter are washed with water, and the hydrazobenzene is extracted from the solids by boiling with 750 ml of ethanol. The mixture is filtered while hot, the filtrate is cooled, the precipitated crystalline hydrazobenzene is filtered with suction, and the mother liquor is used for repeated extraction of the zinc residue. Recrystallization of the crude product from an alcohol-ether mixture gives hydrazobenzene of m.p. 126-127°. 

C. Hydrolysia. Into a three-necked, 5-L, round-bottomed flask equipped with a mechanical stirrer, thermometer, and 500-mL addition funnel with gas Inlet Is placed the above concentrate and 2 L of methanol. The solution is cooled to -5° to 0°C by means of an ice-salt bath. A precooled (0°C) solution containing 220 g of 87.5% potassium hydroxide in 400 raL of water is added dropwise at such a rate as to keep the reaction temperature below 10°C. The reaction mixture is stirred for an additional 2 hr at 0°C and for 1 hr at room temperature prior to the addition of 100 mL of glacial acetic acid. Solid sodium carbonate Is added to bring the pH to 8 and the solution Is filtered through Cellte. Concentration of the filtrate at 35°C and reduced pressure affords about 1 L of a dark liquid. The liquid is diluted with 2 L of water and extracted with petroleum ether (6 x 600 ml). The combined extracts are washed with aqueous sodium thiosulfate solution (800 mL) and dried (magnesium sulfate). Concentration at 30°C affords a clear red liquid (occasionally a yellow solid) which is almost pure internal diester (Note 12). 

To a solution of 17.95 gm (0.0634 mole) of f-butyl-2-(p-bromophenyl) carbazate and 4.94 gm (0.0626 mole) of dry pyridine in 300 ml of methylene chloride is added, in small portions, over a 20 min period, 11.13 gm (0.0551 mole) of N-bromosuccinimide. The red solution is allowed to stand at room temperature for 3 hr. Then the reaction mixture is washed in turn with two portions of 100 ml of water, 125 ml of 10% aqueous sodium hydroxide, and another two portions of water. The product solution is then dried with anhydrous potassium carbonate. The solvent is removed by distillation under reduced pressure, using a water bath at 50°C as the source of heat. On standing, the red liquid crystallizes to a yellow-orange solid which is dissolved in methanol, treated with charcoal, filtered, and the filtrate treated with just sufficient water to cause product precipitation yield 15.34 gm (86%), yellow-orange crystals, m.p. 66°-67°C. 

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