Efficient synthesis of five-membered ring heterocycles using continuous flow devices

ORGN 636

László Cs. Lengyel, laszlo.lengyel@thalesnano.com1, Attila Wootsch1, Ildikó Kovács1, Richard V. Jones1, Elôd Varga1, Tamás Nagy1, László Ürge1, Ferenc Darvas1, and Richard Jones, richard.jones@thalesnano.com2. (1) ThalesNano Inc, H-1031 Záhony u. 7, Budapest, Hungary, (2) Thales Inc, Zahony u. 7, Budapest, 1031, Hungary
Five membered ring heterocycles are important scaffolds in many biologically active compounds. Syntheses of such rings are carried out primarily by a reaction between open-chain bifunctional precursors and a heteroatom containing reagent (applying Knorr, Paal-Knorr synthesis or Lawesson reagent). In batch, these reactions take usually a long time (from 1 to 48 hours). The reaction rate can be accelerated by increasing the temperature. However, in many cases the reagents (e.g. hydrazine derivatives) decompose and form gaseous by-products which evolve in the reaction vessel. Application of high pressure hinders the formation of such by-products and raising the temperature increases the reaction rate.

In the presentation we demonstrate the utility of a high temperature, high pressure continuous-flow reactor in the synthesis of various five-membered heterocyclic building blocks. It can heat and compress solutions up to 350°C and 200 bar, safely, thus, many conventional solvents can be made supercritical under these conditions.