- Thermal Electrocyclic Reactions of 2-Aza-1,3-butadiene Derivatives. A New N-Heterocyclic Annelation
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A general, three-step annelation sequence, which ultimately gives 3,4-dihydro-2-quinolines and related derivatives (3), is described.The cyclization step is accomplished by pyrolysis of a 1-arenyl-2-aza-1,3-butadiene analogue (2) that apparently undergoes successive six-?-electron electrocyclization and 1,5-hydrogen migration reactions to yield the product.The conjugated azadienes, 2, are prepared by the base-catalyzed isomerization of the unconjugated isomers, 1.Compounds 1 are prepared by condensing arenyl ketones or aldehydes with 2-propenyl-1-amine.Steric effects of substituents on the azadiene chain and steric and electronic effects of the arenyl group on the cyclization step were studied.The following general conclusions were drawn: alkyl substituents R on the C=N terminus of 2 hinder a competing degradative process (commencing with a four-?-electron electrocyclization) and improve the yield of products 3; electron-withdrawing substituents on Ar of 2 or electron-withdrawing Ar groups enhance the yield of cyclized products, but they impart little regioselectivity to the reaction; regioselectivity may be imparted by ? bond fixation in Ar; electrocyclization also proceeds well with ?-electron excessive Ar groups on 2.The preferred conformation of the heterocyclic product 3 can be readily deduced by 1H NMR spectroscopy.
- Govindan, C. K.,Taylor, Grant
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p. 5348 - 5354
(2007/10/02)
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- Potential antitumor agents. 13. 4 Methyl 5 amino 1 formylisoquinoline thiosemicarbazone
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4 Methyl 5 amino 1 formylisoquinoline thiosemicarbazone has been synthesized in an attempt to obtain (a) high affinity for the target enzyme ribonucleotide reductase, (b) water solubility as an acid salt of the amine, (c) steric protection of the amino group from in vivo acetylation, and (d) insensitivity to O glucuronidation, a major factor in inactivity in man of 5 hydroxy 2 formylpyridine thiosemicarbazone. The synthesis was achieved by nitration of 1,4 dimethylisoquinoline at the 5 position followed by selective oxidation with selenium dioxide to the corresponding 1 carboxaldehyde. The aldehyde group was protected by conversion to the cyclic ethylene acetal which was then catalytically reduced to produce the 5 amino derivative. Reaction with thiosemicarbazide in the presence of hydrochloric acid yielded the desired derivative. This agent was found to be an effective antineoplastic agent in mice bearing Sarcoma 180 ascites cells and at the maximum effective daily dose of 10 mg/kg increased the average survival of animals threefold over untreated tumor bearing controls.
- Agrawal,Mooney,Sartorelli
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p. 970 - 972
(2007/10/04)
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