Synthesis of new functionalized thiazolo pyridine-fused and thiazolo pyridopyrimidine-fused spirooxindoles via one-pot reactions

Abstract

A sequential multi-component reaction of the nitroketene dithioacetals, cysteamine hydrochloride, isatin and different CH-acids is described. This efficient method provides new functionalized thiazolo pyridine-fused spirooxindoles and thiazolo pyridopyrimidine-fused spirooxindoles in good yields. In the case of using isatin derivatives (5-bromoisatin and 5-chloroisatin), the reaction was carried out by using nano-SiO₂ (20 mol%) as an effective heterogeneous Lewis acid promoter. This type of reaction provides a range of skeletally different polycyclic spiro thiazole-based heterocyclic structures and represents attractive advantages including straightforward one-pot operation under the catalyst-free condition and simple workup procedures without using tedious purification procedure.

Keywords: Isatin; Nano-SiO2; Nitroketene dithioacetals; Organic chemistry; Spiro heterocycles; Spirooxindoles.

Figure 1

A representative of spirooxindole containing drugs.

Figure 2

Selected representative biologically active polycyclic spiro-based compounds.

Scheme 1

Summary of previous studies for the synthesis of pyridine-fused spirooxindoles.

Scheme 2

Synthetic approaches for the formation of products 5 and 6.

Figure 3

SEM image of nano-SiO₂ (a) before and (b) after reuse.

Scheme 3

A plausible mechanism for the synthesis of 5 and 6.

Figure 4

Substrate scope study of functionalized thiazolo pyridine-fused spirooxindoles with a series of isatin and CH-acid compounds.

Figure 5

Substrate scope study of functionalized thiazolo pyridopyrimidine-fused spirooxindoles 6 with a series of isatin.