The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

Abstract

SummaryThe switchable three-component reactions of 5-amino-3-methylisoxazole, salicylaldehyde and N-aryl-3-oxobutanamides under different conditions were studied and discussed. The unexpected influence of the aryl substituent in N-aryl-3-oxobutanamides on the behavior of the reaction was discovered. The key influence of ultrasonication and Lewis acid catalysts led to an established protocol to selectively obtain two or three types of heterocyclic scaffolds depending on the substituent in the N-aryl moiety.

Multicomponent Facile Synthesis of Highly Substituted [1,2,4]Triazolo[1,5-a] Pyrimidines

“…Then, nucleophilic attack of 3-amino-1,2,4-triazole in the presence of the catalyst upon cyclisation afforded the desired product 4a. [28][29][30]…”

Aminoazole-Based Diversity-Oriented Synthesis of Heterocycles

“…Varying the conditions of the reaction and structures of the starting reagents afforded to synthesize three different classes of compounds 166 – 168 from the same reagents (Tkachenko et al, 2014a ). Ultrasonication of 5-amino-3-methylisoxazole ( 60 ), N -aryl-3-oxobutanamide ( 161 ) and salicylaldehyde ( 162 ) afforded N -aryl-4-(3-methylisoxazole-5-ylamino)chromane-3-carboxamides 168 .…”

“…Stirring N -aryl-3-oxobutanamides 161 with R 1 = 2-CH 3 O- or 2-C 2 H 5 O- and compounds 162 and 60 in the presence of Yt(OTf) 3 redirected the condensation toward the formation of dihydroisoxazolopyridines 167 , whereas ultrasonication led to benzoxazocines 166 . This was almost an exceptional case when the replacement of the usual stirring by ultrasonic activation under other identical conditions led to the formation of different compounds (Figure 12 ; Tkachenko et al, 2014a ).…”

“…It's worth to note, that in case of other substituted N -aryl-3-oxobutanamides 161 (R 1 = 2-OH, 2-CH 3 , 2-Cl, 3-Cl) only heterocycles 167 were isolated both with the help of mechanical stirring and under ultrasonication. The authors (Tkachenko et al, 2014a ) suppose that the direction leading to benzoxazocines 166 is favored by the formation of 3-coordinated complex of Yt(OTf) 3 with NH- and CH 3 O(C 2 H 5 O)-groups of carboxamide fragment and OH-group of intermediate tetrahydroisoxazolopyridine. In turn, ultrasound supplies to the reaction system a sufficient amount of energy that is needed for nucleophilic substitution and bridged moiety formation (Figure 12 ).…”