The Wittig Reaction in Industrial Practice

Abstract

The effects of a scientific discovery on industrial practice are illustrated with reference to the Wittig reaction. The aim of utilizing the Wittig reaction for linking terpenoid building blocks to give vitamin A and carotenoids on an industrial scale prompted extensive research and development work of a synthetic and chemical engineering nature. The importance of the Wittig reaction and its variants in the synthesis of active compounds and fine chemicals in industrial research is demonstrated in the present article. Shortly after World War 11, Wittig directed his attention to the question of the existence of pentavalent nitrogen compounds and discovered, in the course of these studies, the nitrogen ylides of type (I) ['].Formation of the nitrogen ylides (I ) was proved by addition to benzophenone (2) to give the (2-hydroxy-2,2-diphenylethy1)trimethylammonium salt (3 ). HX P H( 1 ) + (CBHB)~C=O -(C6H5)2C, CH,-N ( C H~)~X @ (2) (31 Wittig's studies were always highly systematic, and it was therefore only amatter of course that the investigations carried 48 W i t t i g und G e i s s l e ruberraschend war das Verhalten von V gegenuber Benzop hen o n. Bei dieser Umsetzung wurden T r i p hen y 1 -p hosp h ino x y d (etwa 80%) und 1 , l -Diphenyl-iithylen (84%) vom Schmp. 5-6 O (Mischprobe) gewonnen. Danach hat sich die Methylengruppe gegen den Sauerstoff des Ketons vielleicht uber den Vierring VI : ( + ) (C,H,),P + FH. representatives of a new class of compounds. This work led to the first synthesis of crystalline methylenetriphenylphosphorane. When it was attempted to add this product to benzophenone (by analogy with (1)) a surprising new reaction was observed. In a total of six lines of text, Wittig and Geissler described the almost quantitative conversion of methylenetriphenylphosphorane with benzophenone to give triphenylphosphane oxide and 1 ,I-diphenylethylene (Fig. 1).This reaction has since become general chemical knowledge as the Wittig reaction, or Wittig olefination, and it influenced the development of synthetic organic chemistry in the following years to an almost unparalleled degree. It initiated creative activity in laboratories throughout the world as the challenge was taken up to establish the preparative potential of the reaction, to study its mechanistic aspects, e. g. its stereochemistry, or to investigate its effects on neighboring disciplines. The Wittig Reaction and Its Variants in Industrial Practice Process SimplificationThe traditionally close contacts between the chemistry departments of German universities and the chemical industry led to the very early use of the Wittig reaction in industrial practice. At the beginning of the 1950s, when research at BASF was directed toward the development of syntheses for vitamin A and p-carotene, Wittig revealed the new reaction he had discovered in discussions with Reppe and Pommer. Its significance for the synthesis of compounds of the aforementioned kind was quickly recognized. Studies were immediately undertaken with the aim of utilizing the n...

A Wittig Reaction with 2-Furyl Substituents at the Phosphorus Atom: Improved (Z) Selectivity and Isolation of a Stable Oxaphosphetane Intermediate

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Progress in Preparation ofβ,β-Difluorovinyl Compounds

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