kilomentor | 03 July, 2010 15:11
Aldehydes and Ketones are among the most common and best understood functional groups in organic chemistry; however, they can be problematic as intermediates in large scale process chemistry because they are neither markedly acidic nor basic and so cannot be extracted as salts into aqueous solution to achieve purification by phase shifting. During the route planning stage, the synthesis creator cannot readily guess whether these carbonyl intermediates with be crystalline or not. Aldehydes and ketones that are neutral and have no other extraction handle thus are potentially isolation and purification problems. They can turn out to be oils or low melting solids.
Low molecular weight aldehydes and ketones are most often purified by fractional distillation either at atmospheric pressure or under reduced pressure. When they have boiling points in the neighbourhood of 200 C, steam distillation can provide a partial fractionation, but steam distillation is almost always unacceptable because of the very high large point of maximum volume inherent in the procedure. Compounds such as 7-tridecanone [m.p. 30-32.5 C; b.p. 264 C]; 2-pentadecanone [m.p. 7-41 C; b.p. 293 C]; or 2-heptadecanone [m.p. 47-51 C] are representative of these in-between type substances. So although one cannot say with certainty that an intermediate molecular weigh,t neutral carbonyl compounds is going to difficult to separate/purify it is good to have some precautionary potential patches in mind.
Although oximes derivatives of carbonyl compounds are not completely dependably solids, the likelihood that the oxime is a recrystallizable is more than for the carbonyl itself and increases as the number of carbons increases. Shriner, Fuson and Curtin in their classic manual, The Systematic Identification of Organic Compounds, A Laboratory Manual Wiley 1964 report that out of 63 liquid ketones, 44 had solid oximes. Out of 44 liquid aldehydes, 34 had solid oximes, some of which were separated into syn and anti forms.
If the oxime is not a solid, then the possibility for making the oxime hydrochloride adds an additional opportunity to get one’s hands on a crystallizable solid that can be easily converted back into the original carbonyl. It is not routine for synthetic chemists to think of oximes as substances that can be converted into addition salts, because we more typically think of oximes as being reactive with acids to give Beckmann rearrangement products, but in fact the oxime nitrogen is reasonably basic and can produce acid addition salts with mineral and other strong organic acids. These salts can solidify and provide a means of phase shifting (from liquid or solution) to solid that can provide a basis for purification. In Organic Syntheses Coll. Vo. V pg. 266 2-chloro-cyclooctanone oxime in trichloroethylene solution was converted into an oxime hydrochloride by blowing in hydrogen chloride gas. When the solvent was removed the oil solidified to give oxime hydrochloride in 100% crude yield. It seems likely that all that is required to provide an isolable salt is the addition of a strong acid to an anhydrous medium with the oxime. Another non-solid strong acid that could be considered is the liquid acid, dichloroacetic acid.
Whether it is the oxime or the oxime addition salt that is isolated, whether it is as a crystallized or precipitated solid; obtaining the solid provides the opportunity foradequate purification. Then, either the oxime or oxime addition salt can be converted back to the carbonyl in high yield by a variety of well documented treatments. Successful application of this strategy would be one more demonstration of the concept that it is not always the protocol with the fewest identifiably steps, or the fewest chemical reagents, but the one that is simplest to execute and most rugged that is best suited for scale-up and cost minimization.