Mannich, Carl

Mannich, C. Krosche, W. Arch. Pharm. 1912, 250, 647. Carl U. F. Mannich (1877-1947) was bom in Breslau, Germany. After receiving a Ph.D. at Basel in 1903, he served on the faculties of Gottingen, Frankfurt and Berlin. Mannich synthesized many esters of p-aminobenzoic acid as local anesthetics. 

The condensation between an aldehyde, an amine and an active methylene compound, named after Carl Mannich, was first published in 1912 [4]. The products of the reaction, a-amino ketones or Mannich bases are important compounds with numerous applications in the synthesis of pharmaceuticals and of natural products [7]. 

The chemistry of Mannich bases has been associated with pharmacological studies since the early invc.stigations by Carl Mannich, and it is still extensively involved in pharmaceutical chemistry, as is demonstrated by the profusion of papers appearing in specialized publications. The applications of this topic are reported in Chap. V, B, and the present section deals only with natural compounds that function as drugs or vitamins. 

Carl Mannich at the beginning of this century. Indeed, the huge amount of papers published on the matter along with the number of commercially available drugs (Tables 43 and 44) provide signifieant proof of the relevance of such compounds in this branch of industry. 

The first "Mannich reaction took place accidentally in 1912, when Carl Mannich, at that time a young professor in the pharmaceutical laboratory at Gottingen University, was treating with acid the solution of a pharmaceutical preparation based on salicyl antipyrine and urotropinc (hexamethylenetetramine). He obtained a crystalline precipitate, which was later identified, in collaboration with W. Krogen Kroshe, as having the structure shown in Fig. 1. ... 

Ncidlein, R Historisches zu der nach Carl Mannich bcnannten Mannich-reaktion , IXsch. Apoth. Zig., 117. 1215, 1977. 

Professor Wermuth was awarded the Charles Mentzer Prize of the Societe Frangaise de Chimie Therapeutique in 1984, the Leon Velluz Prize of the French Academy of Science in 1995, the Prix de FOrdre des Pharmaciens 1998 by the French Academy of Pharmacy and the Carl Mannich Prize of the German Pharmaceutical Society in 2000. He is Corresponding Member of the German Pharmacentical Society and was nominated Commandeur des Palmes Academiqnes in 1995. He has been President of the Medicinal Chemistry Section of the International Union of Pure and Applied Chemistry (lUPAC) from 1988 to 1992 and from Jannary 1998 to January 2000 was President of the lUPAC Division on Chemistry and Human Health. 

In the Mannich reaction, named for Carl Mannich (1877-1947), an aldehyde or ketone is heated with an acid catalyst in the presence of formaldehyde and an amine. The initially formed ammonium ion is then treated with base to liberate the final condensation product, the free p-amino ketone (Fig. 19.117). 

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