Perspective
The KiloMentor blog has set as a goal to provide free chemical process development information to anyone with web access, anywhere in the world.
The KiloMentor slant on organic synthesis is that excellence in designing separations and purifications that work at scale is really what characterizes the ingenious process chemist. Why is this? There are electronic databases for searching structures and substructures, and for searching reactions, but the process chemist must depend on his/her own understanding and imagination when it comes to designing rugged elegant isolations. This is particularly important because it is the separation, not the reaction that takes most of the processing time.
Once a More Respected Method
Even technologies that in most situations have compelling disadvantages have their use in special circumstances. For example, a first edition laboratory manual, Laboratory Technique in Organic Chemistry, written by Avery Adrian Morton, McGraw-Hill Book Company, Inc. 1938 has an entire chapter devoted to steam distillation. That suggests that methods, which were useful when conditions in chemical sciences were more rudimentary, have a power and ruggedness that might usefully be rejuvenated. Thinking about the reasons that steam distillation is not favored, particularly at scale, finds part of the problem with engineering.
Engineering Disadvantages
First, the large reactor would have to be fitted with a large steam line for superheated steam to deliver the volumes of live steam needed for a high distillation rate.
Second, modern batch-processing condensers are designed for efficient condensation with very small gaps between the condensing plates to recover even low boiling solvents like methylene chloride. The high distillation rates of water and volatile organics (not to mention solids) that could pass over in a steam distillation would quickly flood such condensers and cause a large pressure drop.
Third, if the distillate, now purified turned out to be a solid, which it often does, the condenser would plug. In the laboratory, we can use a different configuration of condensers. With laboratory steam distillation it is normal to have two different kinds of condensers in series. The first condenser has plenty of space in the vapor path where solid can gather before it is swept into the receiver. The second condenser often follows the receiver and traps out efficiently the remaining steam. Diagrams of laboratory set-ups for steam distillation of both liquids and solids can be found online or by consulting the index of the popular chemical synthesis reference text, Fieser & Fieser, Vol. 1 or Organic Synthesis.
Fourth, in a steam distillation set-up, supplemental heating is normally provided to the still pot to prevent condensed steam from accumulating, making heat transfer increasingly difficult. To this must be added the corresponding problem of the tremendous cooling burden on the condensers. The standard multi-purpose reactor and condenser train are not well suited for steam distillation.
Chemical Processing Difficulties
There are chemical processing disadvantages as well. One must deal with a very large volume of condensate containing relatively little product. In steam distillation, the volume at the point of maximum volume limits the number of kilograms per reactor/liter that can be processed. In the early steps of a multi-step process, this will probably constitute a bottleneck because early steps must be repeated a greater number of times even in the best case of batch processing. A steam distillation in one of the early steps of a route almost certainly would seriously limit the throughput.
On the other hand, in the later steps, the need for throughput is much less. In fact, because the product is by now so very expensive relative to the other reaction inputs, a company may not even want to commit a large kilogram charge into a single batch, and so the high point of maximum volume in steam distillation isolation may be of little importance. Note, however, that if the sequence is many steps the accumulating molecular weight of the product may have made the product non-volatile. Steam distillation however could still be used to remove a high boiling reaction solvent.
How does Steam Distillation Compare with Fractional Distillation?
In regular fractional distillation, the fractionation occurs because a column mimics a series of simple distillations in which the distillate from the nth distillation becomes the pot charge for the n+1 th distillation. Since the distillate is always richer in the most volatile component, if sufficient mimics of a simple distillation ( a theoretical plate) are combined in series the more volatile component is eventually obtained pure. If a fractional distillation column is heated too strongly we say the column floods and separation is lost because there is no longer a vapor phase in equilibrium with a liquid phase. Steam distillation is just co-distillation with water under flooding conditions, where there is insufficient vaporization to balance the condensation.
The components come over in the ratio of their vapor pressures as they would in one single simple distillation.
The Benefit of Steam Distillation
For compounds that are too large and too high boiling for simple distillation and that either degrade or are at risk of degrading at their own distillation boiling point even under high vacuum, co-distillation with a large quantity of lower boiling fluid is the only way to vaporize and then recondense them. Steam distillation is just a special case of co-distillation where the cheap low-boiling fluid is water. The other physical requirement for successful steam distillation is that the compound to be distilled must be at least poorly soluble and preferably essentially insoluble in cold water. This preference arises from the need to recover the volatile substance from a massive amount of water co-distillate. Fortunately, most organic target products are poorly water-soluble. It should be noted that all that is actually mandatory is that the product be practically extractable from a large amount of water.
Another traditional use of steam distillation is to remove an otherwise troublesome high-boiling solvent from a reaction mixture so the reaction products can be taken up cleanly in a more manageable, lower-boiling solvent for further processing, most often recrystallization. For example, both nitrobenzene and 1,1,2,2-tetrachloroethane are useful Friedel-Crafts solvents but are infrequently used for crystallization. They are high boiling so both are routinely removed by steam distillation. Other solvents that can be removed by steam distillation are benzyl alcohol, dimethylformamide, methylene bromide, 1,1,2,2-tetrachloroethane, cumene, anisole, cyclohexanone, bromobenzene, collidine, p-cymene, 1,2-dichlorobenzene, aniline, iodobenzene, o-cresol, benzonitrile, nitrobenzene, and quinoline. Together with all the solvents boiling above 100 C that have azeotropes boiling below 100 C, the number of practically useful solvents is increased significantly. This is important because changing solvent is the most frequently effective method of improving overall reaction selectivity.
In some previous blogs, KiloMentor discussed methods to make solvent switches on scale. The transition from a high-boiling, water-immiscible solvent to a lower boiling, water-immiscible can quite generally be cleanly achieved by distilling the high boiling organic with steam and then extracting the non-volatile mixture of product into the lower boiling, water-immiscible organic. This has the advantage compared to azeotropic distillation that the two organics are never mixed together at any point, so recovery and recycling both are possible. That is, there are no intermediate fractions of mixed organic solvents. In this way a solvent switch that in the laboratory, can be done by evaporation of the first solvent solution to dryness can be replaced by (i) concentrating the first solution as much as possible using regular distillation (ii) a short steam distillation to remove the final amount of this first solvent, then (iii) addition of the water-immiscible second solvent to the steam distillation pot residue and (iv) liquid-liquid extraction combining the organic extracts and finally (v) drying the second solvent solution. Such a method could, for example, replace chlorobenzene with methylene chloride or xylene with pentane. The only limitation is that none of the solutes should decompose, polymerize, oxidize, or hydrolyze.
Other Steam Distillation Applications
Another situation where steam distillation can overcome a difficulty arises with a reaction that upon quenching produces a gel that can neither be filtered nor submitted to extraction. Such a difficulty can arise in Friedel-Crafts reactions when aluminum chloride hydrolyzes to silica gel or in lithium aluminum hydride reactions. Steam distillation can get rid of the organic solvent that is gelling with the inorganic material.
Steam distillations are not fractional distillations. Substances that are volatile and form a phase of their own distill over in proportion to their vapor pressures. The only separation is between substances with detectable vapor pressure and substances with no detectable vapor pressure. But steam distillation can be combined with reactive distillation. If two volatile constituents are treated with just sufficient reagent to interact with one of them preferentially and that interaction makes the interacting component non-volatile, the remaining free component can be steam distilled out of the reaction mixture.
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