Revisiting the Ullmann-ether reaction: a concise and amenable synthesis of novel dibenzoxepino[4,5-d]pyrazoles by intramolecular etheration of 4,5-(o,o'-halohydroxy)arylpyrazoles.
A concise synthesis of a series of novel dibenzoxepino[4,5-d]pyrazoles was accomplished by implementation of an intramolecular Ullmann-ether reaction on o,o'-halohydroxy-4,5-diarylpyrazoles mediated by CuBr.DMS. An alternative useful approach based on the palladium-catalyzed biaryl-ether linkage formation (Buchwald-Hartwig reaction) was also successfully applied, offering limitations with regard to the steric demand of the substituents. The synthesis of the key o,o'-halohydroxy-4,5-diarylpyrazole intermediates proceeds through the construction of the heterocyclic ring by a tandem amine-exchange/heterocyclization sequence of 3-N,N-(dimethylamino)-1,2-diarylpropenones with phenylhydrazine followed by basic hydrolysis for deprotection. The enamino ketone precursors were conveniently prepared from the corresponding O-sulfonyloxy and O-benzoyloxy ortho-substituted 1,2-diarylethanones, starting from inexpensive salicylaldehyde or phenylacetic derivatives. Preliminary binding affinity experiments against peripheral and central nervous system receptors have been done with negative results.
Olivera
Roberto
R
Kimika Organikoa II Saila, Zientzi Fakultatea, Euskal Herriko Unibertsitatea, P.O. Box 644, 48080 Bilbao, Spain.
SanMartin
Raul
R
Churruca
Fátima
F
Domínguez
Esther
E
D003989:Dibenzoxazepines / Q000737:chemistry*; D004987:Ethers; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D003989:Dibenzoxazepines; D004987:Ethers; D007202:Indicators and Reagents; D011720:Pyrazoles