Vacuum sublimation processes

Vacuum sublimation is a development of simple sublimation, which is particularly useful if the pressure at the triple-point is lower than atmospheric, where the transfer of vapour from the vaporiser to the condenser is enhanced by the increased driving force attributable to the lower pressure in the condenser. Iodine, pyrogallol, and many metals have been purified by vacuum sublimation processes in which the exit gases from the condenser are usually passed through a cyclone or scrubber to protect the vacuum equipment and to minimise product loss. 

Residual moisture is the low level of water, usually in the range of less than 1-3% (wt/wt), remaining in a freeze-dried product after the freeze-drying (vacuum sublimation) process [1-5] is complete. Nail [6] has described in-process methods to monitor the endpoint of freeze-drying using residual gas analysis, pressure rise, comparative pressure measurement, and product temperature measurement. Roy and Pikal [7] used an electronic moisture sensor inside the lyophilization chamber. Residual moisture [8] content is important in the final freeze-dried product because it affects the potency of the product, its long-term stability, and the official shelf life of the product. 

Dimethylphenol [95-65-8] M 122.2, m 65°, b 225°/757mm, pK 10.36. Heated with an equal weight of cone H2SO4 at 103-105° for 2-3h, then diluted with four volumes of water, refluxed for Ih, and either steam distd or extracted repeatedly with diethyl ether after cooling to room temperature. The steam distillate was also extracted and evaporated to dryness. (The purification process depends on the much slower sulfonation of 3,5-dimethylphenol than most of its likely contaminants.). It can also be crystd from water, hexane or pet ether, and vacuum sublimed. [Kester Ind Eng Chem (Anal Ed) 24 770 1932 Bernasconi and Paschalis J Am Chem Soc 108 29691986.]... 

Freeze-drying, like all drying processes, is a method to separate liquid water from a wet solid product or from a solution or dispersion of given concentration. However, the main difference is that the liquid water is separated by solidification (i.e., the formation of ice crystals) and subsequent vacuum sublimation instead of evaporation. This allows a drying at subzero temperatures which can be advantageous in case of heat-sensitive products. There are two general applications... 

Electrolytic Mg is less pure than Mg obtained by thermal reduction methods and is purified commercially by sublimation under vacuum, a process inherent in thermal reduction. Typical analyses for crude electrolytic Mg (assay 99.8%), for sublimed material (assay 99.95%) and for twice sublimed material (assay 99.99%) are collected in Table l. Sublimation reduces most impurity levels (by 10 ) but leads to increased Zn content. 

Vacuum sublimation is a very popular method for purification of organometallic compounds, because it is so convenient and easy. The sublimation process is not very selective, however, so that it is seldom possible to separate cleanly more than one or perhaps two compounds from a mixture, while in many cases several compoimds occur simultaneously in the irradiated targets. Moreover, annealing may be induced by the heating of the sample for sublimation, although this can be minimized by prior dissolution of the sample to release reactive atoms and... 

Radioactive molecules can sometimes be formed by the processes normally involved in the separation. Foremost among these are (1) exchange in the solvent prior to chromatography and (2) thermal reaction during sublimation. Both lead to false results the second is easily eliminated, the first is often not. As an illustration of the effect of sublimation, it was found (61) that the yield of W(CO)g separated by vacuum sublimation at 50° C was 63.8%. The same irradiation conditions yielded 51.8% when the samples were first chromatographed and then sublimed. Evidence for similar effects was found in (PhH)2Cr (75), RuCpj (29) and others. Simple dissolution to break up the lattice, followed by evaporation and sublimation is usually considered satisfactory to eliminate thermal recombination of initially correlated pairs of reactants. 

The electrochromism of the phthalocyanine ring-based redox processes of vacuum-sublimed thin films of [Lu(Pc)2] was first reported in 1970,32 and since that time this complex has received most attention, although many other (mainly lanthanide) metallophthalocyanines have been investigated for their electrochromic properties.1 Lu(Pc)2 has been studied extensively by Collins and Schiffrin33,34 and by... 

The phases with highest selenium content are the least soluble and the least volatile, allowing fractionation by recrystallization and vacuum sublimation, though it was thought possible that rearrangement reactions occur during these processes. The absorption spectra of these phases have been interpreted to indicate the presence of cyclic Se Sg molecules. All phases exhibit an infrared absorption near 470 cm, typical for SS bonds, which becomes progressively weaker in phases I, II, and III. However, its presence even in phase III which had a selenium content of 68% indicates random distribution rather than alternation of the atoms in the molecules... 

Lyophilization is a process in which a solution of a drug is frozen to a solid and the solvent, usually water, removed by sublimation on exposure to a vacuum. The process has been studied intensively because it can be applied to the preservation of labile drugs or materials such as proteins which would otherwise be adversely affected by the solvent over a period of time. 

Valve I is opened and the trimethylindium is sublimed, under static vacuum, into the 2-L flask (trap-trap distilled). A hot-air gun is used to assist this sublimation process and to ensure that all the trimethylindium is collected on, or near, the surface of the cold, or frozen, amine/petroleum spirit suspension. When all the trimethylindium is trapped into the 2-L flask, valve D is closed to seal the 2-L flask and the rest of the system is filled with air through valve H (make sure valve D is closed ). The liquid nitrogen Dewar is removed and the 2-L flask is disengaged from the rest of the system by careful disconnection between the adaptor housing valve D and the U tube. The top of this adaptor is plugged with a stopper. 

Sublimation (or Primary Drying). For the sublimation phase of the process, the frozen material usually is subjected to a vacuum of about 4.6 millimeters of mercury. The ice-crystal sublimation process can be regarded as comprised of two basic processes (l)Heal transfer, and (2) mass transfer. In essence, heat is furnished to the ice crystals to sublime them he generated waler vapor resulting is transferred out of the sublimation interface. Thus, it is evident thal sublimation will be rare-limited by both resistances to heat and mass transfer as they occur within the material. 

For the sublimation of quantities of materials in the region of a few milligrams, the vacuum sublimation block supplied by Reichert-Jung is particularly suitable. This block is located on the hot-stage microscope (see p. 240), the sublimation chamber carefully evacuated, the temperature raised slowly, and the process of sublimation observed through the microscope. 

Figure 2.5. Schematic of three common methods used to grow single crystals. Shown is (a) diffusion where vapors from a volatile nonsolvent meet the crystallization solvent (b) interfacial where the nonsolvent is layered on top of the crystalhzation solvent (c) sublinration where the solid mixture is heated and the vapors form crystalhtes on the surface of a cold finger. For this latter technique, the crystallization flask may be opened to vacuum throughout the sublimation process (dynamic vacuum), or closed after maintaining initial vacuum to allow slower crystal growth (static vacuum).

---