2238-53-1Relevant academic research and scientific papers
The Synthesis of Heterocycles via Addition-Elimination Reactions of 4- and 5-Aminoimidazoles
Al-Shaar, Adnan H. M.,Chambers, Robert K.,Gilmour, David W.,Lythgoe, David J.,McClenaghan, Ian,Ramsden, Christopher A.
, p. 2789 - 2812 (2007/10/02)
4-Aminoimidazoles 1 undergo addition-elimination reactions with the electrophilic reagents 5-12 to give exclusively N-adducts, which are useful intermediates for further synthetic transformations to novel heterocyclic systems.Diethyl ethoxymethylenemalonate 5 and 4-amino-1-benzylimidazole 1g give the adduct 13g and subsequent acid-catalysed cyclisation gives the imidazopyridine 25 and the heterocyclic mesomeric betaine 26 which undergoes 1,3-dipolar cycloaddition with dimethyl acetylenedicarboxylate to give two products 29 and 30.When the 2-alkyl-4-aminoimidazoles 1b-d are generated in situ in the presence of the reagent 5, signi ficant products are the 5,5'-diimidazoles 15 and a mechanism for this novel transformation is proposed. 4-Amino-3-cyano-imidazopyrimidines 40 and 41 are formed by cyclisation of the N-adducts prepared using ethoxymethylenemalononitriles 6 and 7.Ethoxymethyleneurethane 9 gives the adducts 66 and cyclisation of the parent adduct 66a gives the novel imidazo-1,3,5-triazin-4-one 68a, the potassium salt of which undergoes N-alkylation.The use of the reagents 10-12 leads to novel 4-aminoimidazo-1,3,5-triazine derivatives 72 whose chemical reactions with both electrophilic and nucleophilic reagents are reported. 5-Aminoimidazoles 3 undergo addition-elimination reactions with the electrophilic reagents 5-12 to give N-adducts and/or C-adducts, depending upon the structure of the reagent.These stable addition-elimination products are usually obtained in good yield and are useful intermediates for further synthesis.Reaction of the amines 3 with diethyl ethoxymethylenemalonate 5 gives mainly N-adducts 17 which can be cyclised using phosphoryl chloride to give the versatile 7-chloroimidazopyridines 31.With ethoxymethylenemalononitrile 6 the amines 3 give C-adducts 42.Thermal cyclisa tion of these adducts 42 gives 5-amino-6-cyanoimidazopyridines 43 which are transformed into novel heterocyclic systems including the tricyclic imidazopyridopyrimidines 55.Cyclisation of the adducts obtained using ethoxymethyleneurethane 9 and the N-cyano analogues 10 and 12 provides new synthetic routes to amino-purine derivatives 86 and 87 and hypoxanthines 70.The preference of electrophilic reagents for N- or C-addition to 5-aminoimidazoles 3 is rationalised using Frontier Molecular Orbital theory.
