Telescoping distillation

Eyeglasses, a telescope, and a distillation apparatus—pivotal glass inventions. 

Psychometric procedures like Spearman—Brown provide psychological windows on human variation akin to the microscope in biology and the telescope in astronomy. With an average inter-item correlation of 0.20, a mere 40 item scale can generate a composite whose common (reliable) variance is 91%. This is how psychometrics distils dimensions of common variance for submission to construct validation procedures. 

Briefly, carboxylic acid 14 which must be an essentially pure enantiomer (ratio 98 2) is converted to acid chloride 15 which is an oil that needs to be directly reacted with Meldrum s acid 16 in the presence of 2 moles of pyridine to yield 17 as a stable solid however, a slurry of 17 is treated with glacial acetic acid to provide 18 directly and 17 is not isolated. The process is telescoped in practice, and all the reactions are carried out in dichloromethane, which is recovered and recycled. Thus, 14 is converted into 15 using only a 10% molar excess of oxalyl chloride using 10 mole% of dimethylformamide as catalyst. The reaction is complete after 3 h reaction at room temperature (20 to 25°C) concentration and removal of the dichloromethane yields 15 as a crude oil that is suitable for direct reaction with Meldrum s acid and pyridine at 0 to 5°C in the relative molar ratio 1 2 in fresh dichloromethane. Workup with dilute hydrochloric acid and layer separation followed by water washes results in a solution of 17 in dichloromethane. The solution is concentrated to a slurry, which is treated with acetic acid at about 70 to 80°C to form 18. The reaction mixture is worked up by adding dichloromethane and washing with aqueous sodium carbonate followed by water washes. Concentration of the washed dichloromethane layer yields enantiomer 18 that is equal in optical purity to that of the starting carboxylic acid 14. The concentrate is vacuum distilled to provide a chemically stable and chemically pure ketone 18. This material has been shown to have a shelf life of 5 years at room temperature (Scheme 11.4). 

Evaporation, distillation, and extraction processes are carried out in several stages. Even reactions are carried out in several vessels. Since each stage requires its own auxiliary equipment, telescoping the stages could be highly beneficial. Performing all the reactions in one pot followed by isolation is the most ideal situation. Fermentation is an example of this philosophy, where complex products are formed from simple chemicals. 

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