Four Mechanisms in the Reactions of 3-Aminopyrrole with 1,3,5-Triazines: Inverse Electron Demand Diels–Alder Cycloadditions vs SNAr Reactions via Uncatalyzed and Acid-Catalyzed Pathways

2013 ◽  
Vol 78 (17) ◽  
pp. 8614-8623 ◽  
Author(s):  
Michael De Rosa ◽  
David Arnold ◽  
Douglas Hartline
Keyword(s):  
Diels Alder ◽  
Inverse Electron Demand ◽  
Acid Catalyzed ◽  
Electron Demand

Nucleic Acid Related Compounds. 136. Synthesis of 2-Amino- and 2,6-Diaminopurine Derivatives via Inverse-Electron-Demand Diels-Alder Reactions

2006 ◽  
Vol 71 (7) ◽  
pp. 1029-1041 ◽  
Author(s):  
Xiaoyu Lin ◽  
Morris J. Robins
Keyword(s):  
Nucleic Acid ◽  
Diels Alder ◽  
Curtius Rearrangement ◽  
X Ray ◽  
Inverse Electron Demand ◽  
X Ray Crystallography ◽  
Acid Catalyzed ◽  
Hydrolysis Of ◽  
Related Compounds ◽  
Electron Demand

Thermal inverse-electron-demand Diels-Alder reactions of 5-aminoimidazoles and 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine (2) with spontaneous retro-Diels-Alder loss of ethyl cyanoformate and elimination of ammonia give 2,6-bis(ethoxycarbonyl)purines. A report that selective alkaline hydrolysis followed by acid-catalyzed decarboxylation gave 6-(ethoxycarbonyl)purine products was not in harmony with known reactions in purine chemistry. Our reinvestigation has shown that the 6-(ethoxycarbonyl) group undergoes preferential base-promoted hydrolysis, as expected, but regioselectivity for attack of hydroxide at the carbonyl group at C6 is not high (relative to hydrolysis of both C2 and C6 esters). The structure of 9-benzyl-2-(ethoxycarbonyl)purine was determined by X-ray crystallography and confirmed by Curtius rearrangement of the azidocarbonyl analogue to give 2-amino-6-benzylpurine. Acid-catalyzed decarboxylation of the 2,6-dicarboxylate formed during hydrolysis gave 9-benzylpurine, and Curtius rearrangement of 2,6-bis(azidocarbonyl)-9-benzylpurine gave 2,6-diamino-9-benzylpurine. Attempted applications of inverse-electron-demand Diels-Alder reactions of 2 with nucleoside derivatives were problematic.

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