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-SiO 2 (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.

Expeditious entry into carbocyclic and heterocyclic spirooxindoles

“…A one-pot four-component cascade reaction was accomplished by employing isatin 5d , nitroketene dithioacetals 82 , cysteamine hydrochloride 83 , and active methylene compounds, such as methyl cyanoacetate 14b , ethyl cyanoacetate 14c , malononitrile 14a , cyanoacetohydrazide 14d or barbituric acid 57a . 53 The reaction produces pyridine-fused spirooxindoles 84 on using 14 and thiazolo pyridopyrimidine-fused spirooxindoles 85 on using 57a . The reactivity of the isatin derivatives carrying electron-withdrawing substituent (5-chloroisatin and 5-bromoisatin) was enhanced by choosing nano-SiO 2 as an effective heterogeneous Lewis acid promoter.…”

“…The 1 H decoupled 13 C NMR spectra of 85 showed 16 distinguishable peaks, including peaks at 177.6, 161.1, and 159.6 ppm due to amide carbonyl groups (Scheme 54). 53…”

“…In a similar way, Michael addition takes place between I and new Knoevenagel adduct III followed by intramolecular cyclization of VI and removal of water, forming 85 (Scheme 55). 53…”

“…The 1 H decoupled 13 C NMR spectra of 85 showed 16 distinguishable peaks, including peaks at 177.6, 161.1, and 159.6 ppm due to amide carbonyl groups (Scheme 54). 53 The reaction proceeds via the condensation of 82 and 83 in the presence of triethylamine as a base to afford 2-nitromethylene thiazolidine I. Subsequently, the Michael addition of component I and a Knoevenagel adduct II occurs via the deprotonation of the vinylic acidic hydrogen.…”

One-pot, mild and efficient multicomponent synthesis of novel various spiro-nitrogen heterocycle compounds

“…Heterocyclic chemistry is one of the most complex branches of chemistry and heterocyclic compounds, the largest and most diverse family of chemical compounds. The heterocyclic compounds have a stable structure that cannot be easily hydrolyzed or polymerized [1][2][3]. The heterocyclic compounds are a broad category of ring compounds that contain one or more noncarbon atoms, including nitrogen, oxygen, sulfur, or phosphorus in their structure [4][5][6].…”