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

被引:58
作者
Olivera, R [1 ]
SanMartin, R [1 ]
Churruca, F [1 ]
Domínguez, E [1 ]
机构
[1] Euskal Herriko Unibertsitatea, Zientzi Fak, Kim Organ Saila 2, Bilbao 48080, Spain
关键词
D O I
10.1021/jo025767j
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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-NN-(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.
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页码:7215 / 7225
页数:11
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