188622-49-3Relevant academic research and scientific papers
General preparative route to benzo[g]quinolines (1-azaanthracenes)
Krapcho, A. Paul,Gilmor, Timothy P.
, p. 445 - 452 (2007/10/03)
A convenient synthetic pathway to benzo[g]quinolines (1-azaanthracenes) has been developed. The nickel catalyzed coupling of methyl 2- chloronicotinate (3a) with benzylic organo zinc reagents 2a-e led to the methyl 2-benzylic substituted nicotinates 4a-e. Treatment of methyl 2- chloro-6-methylnicotinate (3b)with 2a in a similar manner led to methyl 2- benzyl-6-methylnicotinate (4f). The coupling of 2-chloro-3-acetylpyridine (5) with benzyl zinc bromide (2a) led to 2-benzyl-3-acetylpyridine (4g). The coupling of the 2,5-dichlorobenzylic organic zinc reagent (2f) with methyl 2- choronicotinate (3a) was unselective but readily coupled with methyl 2- bromonicotinate (6) to yield methyl 2-(2,5-dichlorobenzyl)nicotinate (4h). The esters 4a-f,h on reduction with lithium aluminum hydride led to the corresponding alcohols 7a-f,h which were subsequently oxidized with manganese dioxide to the respective 2-benzylic substituted pyridine-3-carboxaldehydes 8a-f,h. In one case the coupling of benzy] zinc bromide (2a) with 2- chloropyridine-3-carboxaldehyde (9) led directly to 2-benzylpyridine-3- carboxaldehyde (8a), but in poor yield. Cyclizations of the aldehydes 8a- d,f,h or the ketone 4g with polyphosphoric acid afforded the benzo[g]quinolines 10a-d,f-h in high yields. Aldehyde 8e was cyclized to 10e using a solution of sulfuric acid in methanol. Several of the benzo[g]quinolines 10c,d could be readly converted into the benzo[q]quinoline-5,10-diones 11c,d on treatment with ammonium ceric nitrate.
Synthesis of regioisomeric 6,9-(chlorofluoro)-substituted benzo[g]quinoline-5,10-diones, benzo[g]isoquinoline-5,10-diones and 6-chloro-9-fluorobenzo[g]quinoxaline-5,10-dione
Krapcho, A. Paul,Gallagher, Cynthia E.,Hammach, Abdelhakim,Ellis, Michael,Menta, Ernesto,Oliva, Ambrogio
, p. 27 - 32 (2007/10/03)
Treatment of difluoro or chloro fluoro-substituted benzyl bromides 5a-c with zinc dust in tetrahydrofuran leads to the corresponding benzylic zinc bromides 6a-c. These organometallics on treatment with chlorosubstituted heterocyclic esters 4A and 4B mediated by nickel catalysis undergo couplings to yield dihalobenzyl substituted heterocyclic esters 7Aa-c and 7Ba-c. Treatment of 4c with 6c under Pd catalysis leads to 7Cc. The acids 8, prepared by hydrolysis of these esters, with treatment of fuming sulfuric acid undergo cyclizations and oxidations to yield the desired regioisomeric dihalo-substituted heterocyclic quinones 2.
