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The Kilomentor Blog has set its goal to provide free chemical process development information for anyone, anywhere in the world, that has web access. The Kilomentor philosophy is that excellence in designing separation and purification on scale identifies the ingenious process chemist. 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 true because it is the separation not the reaction which occupies the reactor during most of the processing time.

Even technologies that in most situations have overwhelming, can be found useful under particular circumstances. For example, I have a copy of a first edition laboratory manual, Laboratory Technique in Organic Chemistry, written by Avery Adrian Morton, McGraw-Hill Book Company, Inc. 1938. Reading it suggests to me that methods, which were useful when conditions in chemical science were more rudimentary, have a power and ruggedness that can usefully be rejuvenated. Morton has an entire chapter devoted to steam distillation. I was preparing to give a talk at Torcan Chemical Ltd. a division NPIL and I was thinking about the reasons that steam distillation is not favoured, particularly on-scale. It would seem that part of the problem is the engineering. First, the large reactor would have to be fitted with a large steam line for super-heated steam in order to deliver the volume of live steam needed for a high distillation rate. Second, modern batch processing condensers are designed for efficient condensation with very small distances between the condensing plates to recover even low boiling solvents like methylene chloride. The high distillation rates of water and volatile organics from steam distillation would probably flood the condenser and create a large pressure drop. Third, if the distillate now purified turned out to be a solid which it often is, the condenser would plug. In the laboratory we can use a different configuration of condenser.. With laboratory steam distillation set-ups it is normal to have two condensers in series. The first condenser can have plenty of space where solid can gather while the second condenser in series can efficiently trap out the remaining water. Diagrams of laboratory set-ups for steam distillation of liquids as well as solids can be found by consulting the indices of popular chemical synthesis references text such as Fieser & Fieser, Vol 1 or Organic Synthesis. In a steam distillation set-up, supplemental heating is normally provided to the still pot to prevent condensing steam from accumulating and heat transfer is increasingly difficult on scale. To this must be added the corresponding problem of the heat transfer rate needed in the condensers. Efficiency lost is energy lost.

There are chemical processing disadvantages as well. One must deal with very large volumes of condensate containing relative small amounts of product. In a steam distillation, the volume at the point of maximum volume- and this is what limits the number of kilograms/reactor litre that can be pushed through a process step- will be between 70 and 100 or more. In the early steps of a long process, this will probably constitute a bottleneck because these early steps must be repeated the greatest number of times even in the best cases in 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 final steps of a long say 18 step synthetic process, the need for throughput is much less. In fact because the product is by now very expensive, 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 no importance. In the final steps of a long process, yield is everything and if steam distillation can improve yield or maintain yield and increase purity it may be welcomed.

Distillation separates volatile from non-volatile substances based on their relative volatility-that is the traditional pedagogical expression Putting distillation in the context of separation technology we can say that distillation separates a composition, under a particular set of temperature/pressure conditions, that can readily make the phase switch from liquid to gas and back to liquid from a composition that cannot as readily make these transitions. Steam distillation, just from theoretic al considerations, clearly cannot provide fractionation of compounds. If two compounds distil they do so in proportion to their partial pressures. In regular fractional distillation the fractionation occurs because the column mimics a series of simple distillations in which the the distillate from an nth simple distillation becomes the pot charge for the n+1th distillation. Since the distillate is always richer in the more volatile component, if sufficient mimics of a simple distillation (theoretical plate) are combined the more volatile component is final obtained pure. The physical sign that this is occurring in the fractionation column is that the temperature of the column becomes lower the further away from the still pot one moves. It is the continual vaporization and condensation of the volatile gases as they move up the fractionation column that creates the separation. if a fractionation column is heat too strongly in the pot we say they column floods and separation is lost. if the fractionation column is externally heated too strongly there is no condensation in the column and fractionation is lost. Steam distillation is just co-distillation with water under flooding conditions, where there is insufficient condensation.

For compounds that are too large and high boiling for simple distillation and that degrade or at risk to degrade at the normal distillation temperature particularly for the extended times needed for work at scale, supplying a part of the vapor pressure from water allows an organic substance to be mildly taken into the gas phase and recondensed. The other practical requirement for using steam distillation is that the compound to be distilled must be at least poorly soluble and preferably essentially insoluble in cold water. This requirement of course arises from the need to recover the volatile substance from a great deal of water co-distillate. Fortunately most organic target products are poorly water soluble.

Another traditional use of steam distillation is too remove a high boiling solvent from a reaction mixture so the reaction products could be dissolved in a lower boil solvent for further processing, most often recrystallization. For example, both nitrobenzene and 1,1,2,2-tetrachloroethane are useful Friedel-Craft solvents but are infrequently used for crystallizations. Both are difficult to remove, except by steam distillation.

In some previous blogs, Kilomentor discusses methods to make solvent switches on scale. The transition from a high boiling water-immiscible solvent to a lower boiling water-immiscible solvent can quite generally be cleanly achieved by distilling the high boiling organic with steam and then extracting the non-volatile product mixture into the lower boiling water-immiscible organic. The advantage is over azeotropic distillation is: the two organics are not mixed together at any point so recovery and recycling of both is easier. That is there are no intermediate fractions of mixed organics. In this way a solvent switch that in the laboratory is done using evaporation of the first solution to dryness can be replaced by (i) concentrating as much as possible the first solution using regular distillation, (ii) a short steam distillation to remove the final amount of the first solvent, then (iii) addition of the water-immiscible second solvent to the steam distillation pot residue, (iv) liquid-liquid extraction combining the organic extracts and (v)drying of the second solvent. Such a method could for example replace chlorobenzene with methylene chloride or xylene with pentane.

Another situation where steam distillation can provide a separation that is difficult to beat, a reaction that upon quench produces a gel which can neither be filtered or submitted to extraction. Such difficulties can arise in Friedel-Craft reactions when aluminum chloride hydrolyzes to silica gel and in lithium aluminum hydride reactions. Steam distillation gets rid of the organic solvent that is gelling the inorganic material.

As I have noted steam distillation cannot provide clean separations unless one of the components is effectively not volatile. But steam distillation can in principle at least be combined with other chemistry to create a separation methodology. Reactive distillation is a separation process where a mixture of two components is allowed to equilibrate in a reversible reaction with an insufficient amount of a chemical reactant that makes a non-volatile derivative. By using just sufficient reactant to tie up one of the components and continuously distilling the other more volatile component out of the mixture the more volatile or less reactive component is obtained purified in the sdistillate and the less volatile or more reactive component is obtained purified in the still pot. This technique can in principle be nively combined with steam distillation.

Suppose one has a mixture of 2,4-dimethyl quinoline bp. 264-265 C and 4-methyl quinoline bp261-263 C to separate? The compounds are really too similar to be distilled apart at atmospheric pressure or under vacuum. However it is known that if two substances are unequally soluble in water. The more hydrophobic and less soluble is likelt to be somewhat more volatile in steam. This effect is going to be amplified because the 4-methyl quinoline will have less steric hindrance to hydrogen bonding with the water and this will hold it in the still pot. These effects by themselves are not going to deliver a separation because as the distillation proceeds even if the 2,4-dimethylquinoline at first is predominant in the distillate as the still pot becomes increasing richer in 4-methyl quinoline it will become indreasingly present in the rising vapors. Suppose however that we measure the molar ratrion of 4-methyl quinoline to 2,4-dimethyl quinoline by NMR before we begin the distillation with steam and add just sufficient of a none volatile acid to neutralize the 4-methyl quinoline. The 4-methyl quinoline will be the member that is energetically most amenable to forming a salt and remaining dissolved in the aqueous still pot while the less hydrophilic 2,4-dimethyl quinoline will be energetically inclined to desolvate and vaporize. If a proton is too small a Lewis acid to show this effect some metal like copper can be added to the pot in an appropriate amount to selectively complex the 4-methyl quinoline. Now I expect the steam distillation to selectively move the higher molecular weight dimethyl compound to the distillate.

Please note that this is not an actual laboratory result. I am trying to illustrate how one could think to use the technique to devise a separation. Again this is why the skilled process chemist must have a lively working knowledge of all the possible separation methods.

Laboratory equipment costs just a miniscule fraction of that of process equipment. For that reason scientists can perform a reaction which requires strong aqueous alkali in a glass round bottomed flask even though one knows that at the end of the reaction the flask will be opaque and etched by the dissolution of a portion of the glass itself. On the other hand precautions must be taken that a large scale reactor, which is expected to have a long useful life should not be partially dissolved or pitted or weakened by the reactor contents. The process development chemist must never put the reactor at risk. Consideration should be paid early on that reaction conditions are not incompatible with the materials of construction. Engineers are particularly knowledgable in this area and can provide an early warning that particular conditions must be examined. This is normally done in the laboratory by placing weighted tiles of reactor surface material into the laboratory reactor throughout the process step of concern and at the end these tiles are fished out and carefully reweighted. Any experimentally significant difference between the before and after weights is suggestive that the reaction conditions are eroding the reactor surface material. At the same time the experiment will detect any unexpected affect of the reactor material on the course of the process reaction.

Loss of the surface of the reactor can be caused by abrasion where the surface is simply rubbed off and probably remains as fine insoluble particles in side the reactor. Very little can be done about this except to get away from the abrasive reagent. some times this problem can be solved by packing the abrasive agent tightly into a special column and rapidly circulating the solution reaction mixture through the column past the abrasive agent.

Loss of the reactor surface may simple be caused by excessive pHs and this can be controlled by an adjustment in the reactor material itself.

Another cause is the use of or the creation of a very strong chelating agent which simply rips metal ions out of the reactor surface. In such a situation I was able to overcome the corrosion simply by adding a stoichiometric quantity of an inorganic iron salt into the reactor with the rest of the reagents. As the chelator formed it complexed the iron cations and left the reactor alone.

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