Reaction Outcome Critically Dependent on the Method of Workup: An Example from the Synthesis of 1-Isoquinolones
- Petr Matouš*
- Michal Májek
- Ondřej KysilkaOndřej KysilkaTrelleborg Bohemia, Akademika Bedrny 531/8a, Věkoše, 500 03 Hradec Králové Czech RepublicMore by Ondřej Kysilka
- Jiří Kuneš
- Jana Maříková
- Aleš Růžička
- Milan Pour*
- , and
- Pavel Kočovský*Pavel Kočovský*Email: [email protected]Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Prague 2, Czech RepublicDepartment of Bioorganic and Organic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, 166 10 Prague 6, Czech RepublicMore by Pavel Kočovský
A striking dependence on the method of workup has been found for annulation of benzonitriles ArC≡N to N-methyl 2-toluamide (1), facilitated by n-BuLi (2 equiv): quenching the reaction by a slow addition of water produced the expected 1-isoquinolones 2; by contrast, slow pouring of the reaction mixture into water afforded the cyclic aminals 5 (retaining the NMe group of the original toluamide). The mechanism of the two processes is discussed in terms of the actual H+ concentration in the workup. Both 2 and 5 were then converted into the corresponding 1-chloroisoquinolines 3, coupling of which, mediated by (Ph3P)2NiCl2/Zn, afforded bis-isoquinolines 4.
This article has not yet been cited by other publications.