A. Katoh, S. Kondoh, J. Ohkanda
1996
Citations
0
Influential Citations
2
Citations
Journal
Heterocyclic Communications
Abstract
An A/-hydroxyamide-containing heterocycle, 1-hydroxy-4,6-dimethyl-2(1 ̂ -pyrimidinone 1 was allowed to react with benzyl chloroformate (Z-CI) in the presence of pyridine to give the corresponding Obenzyloxycarbonyl-2(1/-/)-pyrimidinone 2. Compound 2 was treated in situ with amines, amino acids, and alcohols under mild conditions to afford Z-protecting products in high yields. Judging from these experimental results, compound 2 was found to be a new convenient benzyloxycarbonylating agent. Introduction The benzyloxycarbonyl (Z) group is one of the most convenient amine protecting group along with fert-butoxycarbonyl (Boc) one, because these urethane-type protection of amino acids is resistant to racemization during peptide syntheses (1,2). The Z-protecting group is easily removed by the catalytic hydrogenation with palladium on carbon. Recently the application of heterocycles to organic synthesis has received considerable attention. For example, pyridine (3), pyrimidine (4), and pyrazine (5-7) have been demonstrated to be useful fert-butoxycarbonylating agents. The utilization of 2-hydroxyand 2-mercaptopyrazines as benzyloxycarbonylating agents has been reported by Ohta and co-workers (8), while no paper concerning 1-hydroxy-2(1 H)-pyrimidinone has been reported, to the best of our knowledge. Since the pKa value of 1-hydroxy-4,6-dimethyl-2(1 Hjpyrimidinone 1 was estimated to be 6.1 (9), its O-acyl derivative is regarded as a kind of the active ester and should be applicable as the new mild acylating agent. As a part of our studies on the application of /V-hydroxyamide-containing heterocycles to organic synthesis (10a), we describe here the utilization of 1-hydroxy-4,6-dimethyl-2(1/-/)-pyrimidinone 1 as a new benzyloxycarbonyl carrier. Results and Discussion 1-Hydroxy-4,6-dimethyl-2(1 H)-pyrimidinone 1 was prepared by condensation of pentane-2,4-dione and /V-benzyloxyurea and subsequent catalytic hydrogenation of 1-benzyloxy-4,6-dimethyl-2(1 H}pyrimidinone (10b). Compound 1 was treated with benzyl chloroformate in the presence of pyridine in CH2CI2 at 0 °C to give the corresponding 0-benzyloxycarbonyl-2(1H)-pyrimidinone 2. In IR spectrum, compound 2 showed two absorption bands at 1810 and 1755 cm" characteristic of the active ester. Since the partial decomposition of compound 2 was observed during isolation, the one-