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Essentially the same directions and apparatus are used in this Skraup synthesis as in the preparation of 8-aminoquinoline. The reaction is much more sensitive and the heat relationships must be more closely guarded and a longer time interval should be allowed.
Two pounds of ground 8-aminoquinoline and 2 pounds of arsenic pentoxide are placed in the reaction vessel, followed by the addition of 4 pounds and 6.2 ounces of dry glycerol. Five pounds and 5 1/3 ounces of concentrated sulfuric acid are now added in small portions through the reflux condenser to the well-stirred glycerol and other substances. The sulfuric acid should not be added at a rate greater than that required to keep the temperature below 100°C, approximately 30 minutes being required. The mixture after the addition of all the sulfuric acid can be gradually heated to 110°C. during 1 hour, and then in 5-degree intervals per hour until a temperature of 135°C. is reached. Finally the temperature is allowed to rise to 140°C., but no higher, and maintained at this point during 2 hours. The temperature control in the case of the second Skraup synthesis should be more carefully and uniformly regulated than in the first for best results.
The cooled Skraup mixture is neutralized as described above, using, however, 40 gallons of solution as final neutralization volume rather than 20 gallons as before. Four and one-third pounds of caustic soda dissolved in 12 gallons of water should be used as neutralizing reagent. Stronger alkali for neutralization is not advised. At a time just preceding the neutralization of the entire batch a green crystalline precipitate of side reaction product forms. As the neutralization proceeds to completion, this green precipitate coagulates to form a more or less rubber-like tar. The extent to which o-phenanthroline is occluded by this tar is a function of the dilution of the solution in which it is formed and of the concentration of the neutralizing alkali added.
The most important controlling factors improving the yield of o-phenanthroline in the process described consist in the recovery of the product occluded by the tar and the preparation of water-soluble o-phenanthroline from the sodium salts in the neutralized Skraup mixture. Treatment of the tar as described in the literature involves drying and extraction for a long time in a Soxhlet extractor with benzene as solvent. This process, together with the formation, under unfavorable conditions, of the tar, which occludes excessive amounts of the desired product, is very tedious and inefficient. The published procedure for the separation of o-phenanthroline from the solution with large amounts of sodium salts involves evaporation of the solution to practically complete separation of the total solids, followed by the extraction of the desired product from the salt mass, using ethyl alcohol. This process involves the formation of considerable quantities of oily impurities and is in general unsatisfactory. Methods by which these two major difficulties can be avoided will now be described.
—The separation of o-phenanthroline from the tar—
The tar formed is soluble in sulfuric acid. Such a solution is prepared and diluted to 6—8 gallons with water, and the acid is then neutralized using dilute sodium hydroxide and a solution temperature of 10°C. The precipitated green crystalline product thus obtained just before the solution is neutralized now contains but little o-phenanthroline and by this process, repeated if necessary, a comparatively pure product can be obtained. The filtered solution of sodium sulfate and o-phenanthroline of approximately 10 gallons volume, if one reprecipitation is applied, is added to the main portion of 40 gallons for subsequent recovery of the indicator base.
—The separation of o-phenanthroline from sodium salts—
Data are not at present available for the solubility of o-phenanthroline monohydrate in water and solutions of sodium sulfate and arsenate at different temperatures. It was originally thought possible to separate the o-phenanthroline from the diluted sulfuric acid solution of the second Skraup reaction products by the addition of ferrous perchlorate or ferrous sulfate, and perchloric acid in sufficient quantity to form the ferrous perchlorate complex. The product thus formed from pure o-phenanthroline can then be oxidized, the ferric iron thus formed removed by precipitation, and the dye base then formed by concentration of the resulting filtrate. This process was not found to be effective, for the reason that the principal impurities are precipitated as the simple perchloric acid salts at the same time. It might well be possible to make the separation of the impurities of the nature previously described by the simple addition of perchloric acid to the dilute acid solution of the Skraup mixture, but the separation of o-phenanthroline from soluble sodium salts would still remain to be accomplished. It was accordingly decided to purify the tar from the neutralized reaction products as previously described, and to take advantage of the high temperature coefficient of the increase in solubility of hydrated o-phenanthroline in boiling aqueous solutions of the sodium salts also present, as compared with the solubility at ordinary temperatures, for the isolation of the desired product.
The 50 gallons of dilute solution of o-phenanthroline, sodium sulfate, and sodium arsenate is evaporated by stages in a 20-gallon, steam-jacketed, enameled, evaporating pan until the boiling solution, upon local cooling through the application of a stream of cold air, shows a cloud of minute crystals giving a milky appearance to the cooled portion of the solution. This occurs when the solution has evaporated to a volume of between 5 and 10 gallons. The reaction mixture is then allowed to cool slowly to room temperature overnight. A large portion of the crystalline o-phenanthroline monohydrate, together with some dark oil, is obtained. The insoluble portion containing the oily impurity is then filtered off, the concentration of the filtrate again carried out as before, and a second and third crop thus obtained. The last filtrate is finally concentrated to the point of crystallization of the inorganic salt content, which is accumulated from batch to batch until it becomes worth while to attempt to remove the last small portion of o-phenanthroline by extraction with hot ethyl alcohol.
The crude o-phenanthroline plus oily impurity is now dissolved in fifty times its weight of boiling water and clarifying carbon added, followed by filtration while still hot. The filtrate is allowed to cool and crystallize, and a second purification carried out to produce a colorless crystal mass of the finished product. The yield thus obtained is found to be 40 per cent, based upon the 8-aminoquinoline taken. The over-all yield based upon the o-nitroaniline used as starting material is thus found to be 20 per cent. The best over-all yield for this synthesis previously reported has been stated to be between 7 and 8 per cent.
© Collected Ruslan Anatolievich Kiper, burewestnik@mail.ru