Zinc(II) perchlorate hexahydrate catalyzed opening of epoxide ring by amines: applications to synthesis of (RS)/(R)-propranolols and (RS)/(R)/(S)-naftopidils.
Commercially available zinc(II) perchlorate hexahydrate [Zn(ClO4)2.6H2O] was found to be a new and highly efficient catalyst for opening of epoxide rings by amines affording 2-amino alcohols in high yields under solvent-free conditions and with excellent chemo-, regio-, and stereoselectivities. For unsymmetrical epoxides, the regioselectivity was influenced by the electronic and steric factors associated with the epoxides and the amines. A complementarity in the regioselectivity was observed during the reaction of styrene oxide with aromatic and aliphatic amines: aromatic amines provided amino alcohols from nucleophilic attack at the benzylic carbon as major products whereas aliphatic amines resulted in formation of the amino alcohols through reaction at the terminal carbon atom of the epoxide ring as the major/sole products. Reaction of aniline with various glycidic ethers gave the amino alcohols by regioselective nucleophilic attack at the terminal carbon atom of the epoxide ring as the only/major product. Zinc(II) perchlorate hexahydrate was found to be the best catalyst compared to other metal perchlorates. The counteranion modulated the catalytic property of the various Zn(II) compounds that followed the order Zn(ClO4)2.(6)H2O>>Zn(BF4)2 approximately Zn(OTf)2>>ZnI2>ZnBr2>ZnCl2>Zn(OAc)2>Zn(CO3)2 in parallelism with the acidic strength of the corresponding protic acids (except for TfOH). The applicability of the methodology was demonstrated by the synthesis of cardiovascular drugs propranolol and naftopidil as racemates and optically active enantiomers.
Shivani
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar 160 062, Punjab, India.
Pujala
Brahmam
B
Chakraborti
Asit K
AK
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D004811:Epichlorohydrin / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D010472:Perchlorates / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D011433:Propranolol / Q000138:chemical synthesis* / Q000737:chemistry; D017967:Zinc Compounds / Q000737:chemistry*
D000588:Amines; D004852:Epoxy Compounds; D008670:Metals; D009281:Naphthalenes; D010472:Perchlorates; D010879:Piperazines; D017967:Zinc Compounds; C520702:zinc(II) perchlorate hexahydrate; D004811:Epichlorohydrin; D011433:Propranolol; C064357:naftopidil