Pyridine synthesis via Diels-Alder reaction of 1-AZA-1,3- butadienes & total synthesis of 7-bromolavendamycin methyl ester

• Main Author: Ahmadian, Mohammad
• Other Authors: Ball State University. Dept. of Chemistry.
• Format: Others
• Published: 2011
• Subjects: Pyridine > Synthesis.; Diels-Alder reaction.
• Online Access: http://cardinalscholar.bsu.edu/handle/handle/184382; http://liblink.bsu.edu/uhtbin/catkey/834525

A methodology for the synthesis of substituted pyridines via Diels-Alder condensation of N-(O-tbutyldimethylsilyloxy)-3-methyl-l-aza-1,3-butadiene (65) and N-(O-tbutyl dimethylsilyloxy)-2-methyl-l-aza-1,3-butadiene (66) with substituted 1,4-benzoquinones was developed.The novel azadienes 65 and 66 were synthesized by direct condensation of N-(Otbutyldimethylsilyloxy) hydroxylamine with methacrolein and methyl vinyl ketone respectively. The azadiene 66 was also prepared by condensation of N-(O-tbutyldimethylsilyloxy) hydroxylamine with 3-bromo-2-butanone followed by dehydrohalogenation of the resulting imine with potassium tbutoxide.The Diels-Alder condensation of 66 with N-phenylmaleimide produced N-phenyl-6methyl-2,3-pyridinedicarboximide (82). The [4+2] cycloaddition of 66 with Nphenylmaleimide, naphthoquinone, 2-acetamido-5-bromo- and 2-acetamido-6-bromo-1,4benzoquinone, 2,6-dichloro-1,4-benzoquinone, 2-bromo- 1,4-benzoquinone resulted in the formation of N-phenyl-5-methyl-2,3-pyridinedicarboximide (83), 3-methyl-lazaanthracene-9,10-dione (87), 6-acetamido-3-methylquinoline-5,8-Dione (90), 7acetamido-3-methylquinoline-5,8-dione (91), 7-chloro-3-methylquinoline-5,8-dione (93), 3-methylquinoline-5,8-dione (95) respectively. Diels-Alder condensation of 2,6-dibromo 1,4-benzoquinone with azadienes 65 and 66 produced some non-isolable tar. Total synthesis of 7-bromolavendamycin methyl ester 33 was also attempted. Although all attempts to obtain the key intermediate, 7-bromo-2-methyl-5,8-quinolinedione (98a), either from the Diels-Alder condensation of 66 or oxidation of 5,7-dibromo-2-methyl-8hydroxy quinoline (99) failed, 98a was synthesized through oxidation of 5-amino-7bromo-2-methyl-8-hydroxyquinoline (104). Selective oxidation of 98a with SeO2 produced 7-bromo-2-formylquinoline-5,8-dione (98b). Pictet-Spengler condensation of 98b with p-methyl trypthophan methyl ester (55), gave the tetrahydrocarboline 106 which was decomposed in refluxing benzene.In a different pathway, 103 was selectively oxidized to 7- bromo-2- form yl -5-ni tro8-hydroxyquinoline (107b). Condensation of this aldehyde with p-methyl tripthophan (55), produced 3-carbomethoxy-4methyl-l-(7-bromo-8-hydroxy-5-nitro-2-quinolinyl)-(3carboline (109a). 3-Carbomethoxy-4-methyl-l-(7-bromo-8-hydroxy-5-amino-2quinolinyl)-p-carboline (109b) was obtained by reduction of 109a. It is expected that 7bromolavendamycin methyl ester 33 to be produced by oxidation of 109b.The structures of the new compounds were confirmed by NMR, IR and mass spectroscopy as well as the elemental analysis. All the spectra are included at the end of this thesis for further reference. === Department of Chemistry