Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones
| Autor: | Hakan Gunaydin, Bingfan Du, Victor J. Cee, Philip R. Olivieri, Stephanie D. Geuns-Meyer, Kathleen Panter Faber, Brian L. Hodous, Vinod F. Patel, Holly L. Deak, Hanh Nho Nguyen, Paul H. Krolikowski, Steven L. Hollis, Karina Romero, Laurie B. Schenkel |
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| Rok vydání: | 2012 |
| Předmět: |
chemistry.chemical_classification
Halogenation Molecular Structure Aryl Organic Chemistry Hydrazine Phthalimides Stereoisomerism Isoindoles Ring (chemistry) Benzoates Combinatorial chemistry Catalysis 2-pyrazolylbenzoic acid chemistry.chemical_compound Hydrazines chemistry Reagent Phthalazines Pyrazoles Organic chemistry 2-pyrazolylbenzohydrazide Alkyl |
| Zdroj: | The Journal of Organic Chemistry. 77:3887-3906 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo3000628 |
| Popis: | Herein we describe a general three-step synthesis of 4-substituted chlorophthalazines in good overall yields. In the key step, N,N-dimethylaminophthalimide (8a) directs the selective monoaddition of alkyl, aryl, and heteroaryl organometallic reagents to afford 3-substituted 3-hydroxyisoindolinones 9b, 9i-9am. Many of these hydroxyisoindolinones are converted to chlorophthalazines 1b-1v via reaction with hydrazine, followed by chlorination with POCl(3). We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to N,N-dimethylaminophthalimide (8a) provided dihydrobenzoazepinediones 15a-15c via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and substituted hydrazines to afford 2-pyrazolyl benzoic acids 16a-16d and 2-pyrazolyl benzohydrazides 17a-17g rather than the expected alkynyl phthalazinones. |
| Databáze: | OpenAIRE |
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