Synthesis of unsymmetrical substituted 1,4-dihydropyridines through thermal and microwave assisted [4+2] cycloadditions of 1-azadienes and allenic esters.
Thermal and microwave assisted [4+2] cycloadditions of 1,4-diaryl-1-aza-1,3-butadienes with allenic esters lead to cycloadducts, which after a 1,3-H shift afford variedly substituted unsymmetrical 2-alkyl-1,4-diaryl-3-ethoxycarbonyl-1,4-dihydropyridines in high yields. Reactions carried out under microwave irradiation are cleaner and give higher yields with much shortened reaction times. Density functional theory (DFT) at the B3LYP/6-31G* level has been used to calculate geometric features of the reactants, barrier for s-trans to s-cis and reverse isomerization of azadienes (5a-d, 10a-e), dihedral angles between N(1), C(2), C(3), and C(4) atoms of azadienes along with various indices such as chemical hardness (eta), chemical potential (micro), global electrophilicity (omega), and the difference in global electrophilicity (Deltaomega) between the reacting pairs and Fukui functions (f (+) and f(-)). The results revealed that s-trans is the predominant conformation of azadienes at ambient temperature and the barrier for conversion of the s-trans rotamer of 1-azadienes to s-cis may be the major factor influencing the chemoselectivity, i.e., [4+2] verses [2+2] cycloaddition. The regiochemistry of the observed cycloadditions is collated with the obtained local electrophilicity indices (Fukui functions). Transition states for the formation of both [4+2] and [2+2] cycloadducts as located at the PM3 level indicate that the transition state for the formation of [4+2] cycloadducts has lower energy, again supporting the earlier conclusion that preferred formation of [4+2] cycloaaducts at higher temperature may be a consequence of barrier for s-trans to s-cis transformation of 1-azadienes.
Singh
Lakhwinder
L
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India.
Ishar
M P Singh
MP
Elango
Munusamy
M
Subramanian
Venkatesan
V
Gupta
Vivek
V
Kanwal
Priyanka
P
D000466:Alkadienes / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry*; D002070:Butadienes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D006358:Hot Temperature; D008872:Microwaves; D008958:Models, Molecular; D008968:Molecular Conformation; D013816:Thermodynamics
D000466:Alkadienes; D001372:Aza Compounds; D002070:Butadienes; D004095:Dihydropyridines; D004952:Esters; C025947:propadiene; C038806:1,4-dihydropyridine