Freezing resistance cooling rate

Quality achievement requires that cooling rates, temperature levels, final mean moisture contents and water gradients through the dried-out cake should be carefully controlled all along the freeze-drying process. Uncontrolled temperature levels can induce undesirable color changes and, principally, material collapse with a loss of mechanical resistance and therapeutic activity. 

In a 2-1. round-bottom flask, fitted with a stopper holding a dropping funnel and a mechanical stirrer, is placed a mixture of 275 cc. of concentrated nitric acid (sp. gr. 1.42) and 275 cc. of concentrated sulfuric acid (sp. gr. 1.84). This is cooled to io° in a freezing mixture, and 100 g. of benzyl cyanide (free from alcohol and water) are run in slowly, at such a rate that the temperature remains at about io° and does not exceed 20°. After all the benzyl cyanide has been added (about one hour), the ice bath is removed, the mixture is stirred for an hour and then poured on to 1200 g. of crushed ice. A pasty mass slowly separates more than half of this mass is -nitrobenzyl cyanide, the other constituents being o-nitrobenzyl cyanide, and a variable amount of an oil which resists hydrolysis apparently no dinitro compounds are formed. The mass is filtered on a porcelain funnel with suction, pressed well to remove as much oil as possible, and dissolved in 500 cc. of boiling alcohol (95 per cent). On cooling, -nitrobenzyl cyanide crystallizes the mother liquor, on distillation, gives an impure alcohol which can be used for the next run. Recrystallization from 550 cc. of 80 per cent alcohol (sp. gr. 0.86 to 0.87) yields 70 to 75 g. (50-54 per cent) of a product which melts at 115-116°. 

---