- 'Green' synthesis of 2-substituted 6-hydroxy-[3H]-pyrimidin-4-ones and 4,6-dichloropyrimidines: Improved strategies and mechanistic study
-
An improved route to 2-substituted 6-hydroxy-[3H]-pyrimidin-4-ones 4 and to 2-substituted 4,6-dichloropyrimidines 5 is reported. Without using highly toxic reactants, compounds 4 can be prepared conveniently in a one pot synthesis on a one mol scale with average yields up to 80%. 4,6-Dichloropyrimidines 5, which are usually prepared in small quantities, are synthesized with average yields of 80%, using up to 80g of starting material. The mechanism of the chlorination of 4 is investigated computationally for the first time. The results suggest that the chlorination with phosphoryl chloride occurs in an alternating phosphorylation-chlorination manner (pathway 1) which is preferred over a sequence which starts with two phosphorylations. The investigated 4,6-dichloropyrimidines described herein form strong complexes with dichlorophosphoric acid but weak complexes with hydrochloric acid (generated during workup). These latter complexes explain the necessity of using aqueous sodium carbonate during the working up. In order to prevent possible formation of pyrimidinium salts between intermediates or the final dichloropyrimidines and unreacted hydroxypyrimidone, the latter could be deactivated with a strong acid such as dichlorophosphoric acid, thus allowing chlorination but prohibiting salt formation. Because of its general applicability to all nitrogen heterocycle chlorinations with phosphoryl chloride, the proposed route to dichloropyrimidines without solvent or side products, using less toxic reactants, is of general synthetic interest.
- Opitz, Andreas,Sulger, Werner,Daltrozzo, Ewald,Koch, Rainer
-
p. 814 - 824
(2015/05/20)
-
- Ethylene bis-imidazoles are highly potent and selective activators for isozymes VA and VII of carbonic anhydrase, with a potential nootropic effect
-
A series of ethylene bis-imidazoles was synthesized via a novel microwave-mediated synthesis. Biological testing on eight isozymes of carbonic anhydrase (CA) present in the human brain revealed compounds with nanomolar potency against CA VA and CA VII, also displaying excellent selectivity against other CA isozymes present in this organ. the Partner Organisations 2014.
- Draghici, Bogdan,Vullo, Daniela,Akocak, Suleyman,Walker, Ellen A.,Supuran, Claudiu T.,Ilies, Marc A.
-
p. 5980 - 5983
(2014/05/20)
-
- Preparation of 2-amino-4-alkoxy-s-triazines
-
2-Amino-4-alkoxy-s-triazines which are substituted by an alkyl, aryl or aralkyl moiety in the 6-position and which are useful as pharmaceutical agents and as intermediates for herbicides, dyes and optical brighteners are prepared by reacting a dialkyl (N-cyanoimido)carbonate with an amidine salt in the presence of an inert solvent and a base.
- -
-
-