Efficient synthesis of selected phthalazine derivatives
-
Richard A. Bunce
,
Todd Harrison
Abstract
Four phthalazine derivatives have been prepared from substituted 2-bromobenzaldehyde acetals by a sequence involving: (1) lithiation and formylation; (2) deprotection; and (3) condensative cyclization with hydrazine. Two additional phthalazines were prepared by a similar sequence following direct lithiation of benzaldehyde acetals substituted by anion-stabilizing groups at C3. These syntheses can be conveniently carried out to give phthalazines in overall yields of 40–70%.
T.H. gratefully acknowledges the Department of Chemistry at Oklahoma State University (OSU) for a teaching assistantship. Funding for the 300-MHz NMR spectrometers of the Oklahoma Statewide Shared NMR Facility was provided by NSF (BIR-9512269), the Oklahoma State Regents for Higher Education, the W.M. Keck Foundation, and Conoco, Inc. The authors also wish to thank the OSU College of Arts and Sciences for funds to upgrade our departmental FT-IR and GC-MS instruments.
References
Balczewski, P.; Koprowski, M.; Bodzioch, A.; Marciniak, B.; Rozycka-Sokolowska, E. Unusual transformation of the diarylmethanol derivative into an unknown 1,2,3,6,7,10-hexahydroxylated anthracene system. J. Org. Chem. 2006, 71, 2899–2902.10.1021/jo052599xSearch in Google Scholar PubMed
Bhattacharjee, D.; Popp, F. D. New compounds: Reissert compound studies XXXII: facile synthesis of 3-azapapaverine. J. Pharm. Sci. 1980, 69, 120–121.10.1002/jps.2600690140Search in Google Scholar PubMed
Bourne, C. R.; Bunce, R. A.; Bourne, P. C.; Berlin, K. D.; Barrow, E. W.; Barrow, W. W. Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity. Antimicrob. Agents Chemother. 2009, 53, 3065–3073.10.1128/AAC.01666-08Search in Google Scholar PubMed PubMed Central
Charlton, J. L.; Oleschuk, C. J.; Chee, G.-L. Hindered rotation in arylnaphthalene lignans. J. Org. Chem. 1996, 61, 3452–3457.10.1021/jo952048eSearch in Google Scholar
Dallacker, F.; Glombitza, K.-W.; Lipp, M. Derivate des methylenedioxybenzols, IV. Reacktionen des 4,5-methylendioxy-phthalaldehyds. Liebigs Ann. Chem. 1961, 643, 82–90.10.1002/jlac.19616430111Search in Google Scholar
Dellaria, J. F., Jr. Urokinase inhibitors. U.S. Patent 6,207,701, 2001. Chem. Abstr. 2001, 134, 252255.Search in Google Scholar
Gschwend, H. W.; Rodriguez, H. R. Heteroatom-facilitated lithiations. Organic React.1979, 26, 1–360.10.1002/0471264180.or026.01Search in Google Scholar
Hirsch, A.; Orphanos, D. Convenient quantitative preparation of phthalazine. J. Heterocycl. Chem. 1965, 2, 206.10.1002/jhet.5570020219Search in Google Scholar
Kalesse, M. Synthesis abstract no. 5. Amberlyst® 15 as a catalyst in synthetic organic chemistry. Acros Organic Acta1995, 1, 67–68.10.1002/chin.199617275Search in Google Scholar
Kessar, S. V.; Vohra, R.; Kaur, N. P. Lewis acid complexed heteroatom carbanions; a convenient route to α-hydroxybenzyltetrahydroisoquinoline alkaloids. Tetrahedron Lett. 1991, 32, 3221–3224.10.1016/S0040-4039(00)79728-0Search in Google Scholar
Moody, C. J.; Warrellow, G. J. Vinyl azides in heterocyclic synthesis. Part 10. Synthesis of the isoindolobenzazepine alkaloid lennoxamine. J. Chem. Soc. Perkin Trans.1990, 1, 2929–2936.10.1039/p19900002929Search in Google Scholar
Omata, K.; Tomita, H.; Nakajima, T.; Natsume, B. Design of new melanin biosynthesis inhibitors. Pest. Sci.1989, 26, 271–281.10.1002/ps.2780260307Search in Google Scholar
Pappas, J. J.; Keaveney, W. P.; Berger, M.; Rush, R. V. Directional effects of substituents in the ozonolysis of naphthalenes. Synthesis of o-phthalaldehydes. J. Org. Chem. 1968, 33, 787–792.10.1021/jo01266a063Search in Google Scholar
Remy, D. C.; King, S. W.; Cochran, D.; Springer, J. P.; Hirshfield, J. Facile intramolecular tosylhydrazone-mediated cyclopropanation reaction of 4-(2-formylphenyl)-1,4-dihydropyridines. J. Org. Chem. 1985, 50, 4120–4125.10.1021/jo00221a030Search in Google Scholar
Robev, S. Phthalazine derivatives from aromatic aldazines. Tetrahedron Lett. 1981, 22, 345–348.10.1016/0040-4039(81)80093-7Search in Google Scholar
Rohm and Haas Co. Technical bulletin fluid process chemicals: Amberlyst® 15 synthetic resin catalyst, 1978.Search in Google Scholar
Tsoungas, P. G.; Searcey, M. A convenient access to benzo-substituted phthalazines as potential precursors to DNA intercalators. Tetrahedron Lett. 2001, 42, 6589–6592.10.1016/S0040-4039(01)01302-8Search in Google Scholar
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Articles in the same Issue
- Supplementary data
- Masthead
- Masthead
- Preliminary Communications
- Synthesis and molecular structure of (Z)-1H-purin-6-ylideneaminooxysulfonic acid: a possible secondary metabolite of adenine
- Design and synthesis of heterocyclic enamine derivatives based on skeleton of neonicotinoids
- Research Articles
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- Efficient synthesis of selected phthalazine derivatives
- Synthesis of novel fluorescent 1,3,5-trisubstituted triazine derivatives and photophysical property evaluation of fluorophores and their BSA conjugates
- Fast and efficient microwave synthetic methods for some new 2(1H)-pyridone arabinosides
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- Palladium-catalyzed cascade reactions of benzyl halides with N,N-diallyl-p-toluenesulfonamide
- Iodine-catalyzed synthesis of 5-arylanthra[2,1-c][2,7]naphthyridine derivatives via three-component reaction
- One-pot synthesis of acenaphtho[1,2-b]pyrroles in the presence of supported ionic liquid catalyst
- Theoretical investigation on tautomerism and NBO analysis of 3-hydroxy-1,2,5-thiadiazole derivatives: solvent and substituent effects
Articles in the same Issue
- Supplementary data
- Masthead
- Masthead
- Preliminary Communications
- Synthesis and molecular structure of (Z)-1H-purin-6-ylideneaminooxysulfonic acid: a possible secondary metabolite of adenine
- Design and synthesis of heterocyclic enamine derivatives based on skeleton of neonicotinoids
- Research Articles
- Reductive amination of 6-acetylpteridine to 6-N-arylaminoethylpteridine
- Efficient synthesis of selected phthalazine derivatives
- Synthesis of novel fluorescent 1,3,5-trisubstituted triazine derivatives and photophysical property evaluation of fluorophores and their BSA conjugates
- Fast and efficient microwave synthetic methods for some new 2(1H)-pyridone arabinosides
- Simple and efficient synthesis of novel N-dichloroacetyl-3,4-dihydro-2H-1,4-benzoxazines
- Palladium-catalyzed cascade reactions of benzyl halides with N,N-diallyl-p-toluenesulfonamide
- Iodine-catalyzed synthesis of 5-arylanthra[2,1-c][2,7]naphthyridine derivatives via three-component reaction
- One-pot synthesis of acenaphtho[1,2-b]pyrroles in the presence of supported ionic liquid catalyst
- Theoretical investigation on tautomerism and NBO analysis of 3-hydroxy-1,2,5-thiadiazole derivatives: solvent and substituent effects
