Study On The 3-CR Methodology Of 2-(Benzo[D] Thiazole-2-YL) Acetonitrile And Heterocyclic Ketene Aminals As Synthon

Owing to the special structure and high reactivity of 2-(benzo[d]thiazole-2-yl)- acetonitrile andβ-(2-chloroaroyl)-heterocyclic ketene aminals, we herein developed an excellent strategy for for the synthesis of 4H-benzo[b]pyrans, tetrahydroimidazo -[1,2-a]pyridines and 1,8-naphthyridines derivatives. Judging from the diversity-oriented synthesis (DOS), this method is flexible, which includs the advantages of high chemo- and regioselectivity and high bond-forming efficiency. The novel domino and multicomponent reactions are the most enabling synthetic tools to enhance the synthesis of 4H-benzo[b]pyrans, tetrahydroimidazo[1,2-a]pyridines and 1,8-naphthyridines derivatives.In this paper, one-pot, three-component reaction to synthesis 4H-benzo[b]pyrans derivatives by using basic ionic liquid [bmIm]OH as catalyst was developed. Series tests were carried out in order to compare ionic liquid ([bmIm]OH) with organic, inorganic base and [bmIm]BF4, [bmIm]BF4/KOH as catalysts, 2-(benzo[d]thiazole -2-yl)acetonitrile, aromatic aldehyde, and 5,5-dimethyl-1,3-dicyclohexone to synthesize 4H-benzo[b]pyrans derivatives (I6a-p) via one-pot, three-component reaction. The results show that the excellent yields (95%) were obtained by 60mol% [bmIm]OH as catalyst, and the products were simply purified. This eco-friendly method hasn't been reported so far.Becaues of the high reactivity ofβ-(2-chloroaroyl)-heterocyclic ketene aminals, forty new tetrahydroimidazo[1,2-a]pyridines (II4a-l, II8a-h) and 1,8-naphthyridines (II5a-l, II9a-h) derivatives were synthesized using it as versatile building blocks by the combined use of domino and MCRs reactions. Solvents and catalysts were investigated; the results show that the excellent yields (80%) were obtained by 20 mol% Et3N as catalyst, acetonitrile as solvent. In this reaction, seven different active sites were involved; two C-C bonds, two C-N bonds and two new rings were constructed with all reactants which efficiently utilized via a sequence of Knoevenagel condensation, Michael addition, cyclization and intramolecular nucleophilic substitution reactions. It fully reflects the"atom economy"of this reaction.Fifty-six compounds were synthesized, and the structures of all the synthesized compounds were characterized by IR, 1H NMR, 13C NMR and elemental analysis, some of them were further confirmed by MS spectrum. The unambiguous molecular structure of II9a was determined by X-ray diffraction analysis. The plausible mechanism was also presented.