A Practical Synthesis of 3‐Functionalized Coumarins from o‐Cresols and Active Methylene Compounds under Metal and Catalyst‐Free Conditions Using tert‐Butyl Hydrogen Peroxide

Abstract

An efficient synthesis of 3-functionalized coumarins is demonstrated from o-cresols and active methylene compounds under solvent-, metal-and catalyst-free conditions in the presence of 70 % aqueous tert-butyl hydrogen peroxide. The important features of this protocol are operational simplicity, mild reaction conditions and good to excellent yield of the products.Coumarin scaffold is well regarded parent compound present in several natural products and bioactive molecules. [1] Coumarin derivatives possess a wide range of biological activities including antibacterial, antifungal, anti-HIV, antioxidant, anticancer, analgesic and anti-inflammatory activities (Figure 1). [2] Coumarin scaffold also incorporated in insecticides, fragrances, perfumes, agrochemicals and used as additives in foods and cosmetics. [3] On the other hand, numerous coumarins compounds were explored as light-harvesting molecules, lightemitting diodes, triplet oxygen sensitizers, fluorescent probes, etc. [4] Hence, coumarin is very imperative building block for combinatorial library synthesis.Synthesis of these oxygen containing heterocyclic compounds usually executed by numerous methods including the von Pechmann, Knoevenagel, Perkin and Wittig reactions. [5,6] Knoevenagel condensation is not only an alternative, but also an efficient method for the synthesis of 3-substituted coumarins from salicylaldehyde with active methylene compounds like meldrum acid, malonate esters, ethyl cyanoacetate, etc. [6] Synthesis of 3-substituted coumarins via Knoevenagel condensation was achieved using different metal and metal-free catalyst like ZrCl 4 , MgÀ Al hydrotalcite, mesoporous molecular sieve MCM-41, p-toluenesulphonic acid, natural clay, PhI(OAc) 2 L-proline, NaOH, piperidine, MgFe 2 O 4 nanoparticles (Scheme 1, A). [1,5,6] However, most of these methods have their own merits and demerits.

Synergistic Effect of Cerium in Dual Photoinduced Ligand-to-Metal Charge Transfer and Lewis Acid Catalysis: Diastereoselective Alkylation of Coumarins

“…Ethyl 6-chloro-2-oxo-2 H -chromene-3-carboxylate ( 2d ) was prepared following GP1 , starting from 5-chloro salicylaldehyde and diethyl malonate. The product was purified via recrystallization from ethanol, affording 2d as a light-yellow solid (1.13 g, 90% yield).…”

Biomass‐derived Sugar Ionic Liquid as a Sustainable Organocatalyst: An Efficient Synthesis of Functionalized Dihydropyrano Coumarins

“…A plethora of review reports are there on the synthesis of dihydropyrano coumarin derivatives via one pot reaction of aromatic malononitrile, aldehydes and CÀ H active acids in the presence of homogeneous or heterogeneous catalysts such as organic acids or bases, nanoparticles, zeolites, and Ionic liquids. [25][26][27] Numerous catalysts such as 1,4diazabicyclo[2.2.2]octane (DABCO), [11] ammonium acetate, [28] 1,8diazabicyclo[5.4.0]undec-7-ene (DBU), [29] urea, [30] piperzine, [31] triethylbenzylammoniumchloride (TEBA), [32] diammonium hydrogen phosphate, [33] piperidine, [34] ammonium/sodium formate, [35] 2-hydroxyethylammonium formate, [36] CuO, [37] sodium tungstate, [38] Fe 2 O 3 , [39] GN/SO 3 H, [40] oxo-vanadium phthalocyanine, [41] Ti 2 O, [42] cobalt orthophosphate (Co 3 (PO 4 ) 2 ), [43] tert-butyl hydrogen peroxide, [44] cyclodextrin, [45] 1-butyl-3-methylimidazolium triflate [46] and many more have been reported for the synthesis of dihydropyrano coumarins. Yousefi et al prepared pyranocoumarins by employing piperzine as a catalyst (Scheme 1a).…”

A chromatography-free one-pot, two-step synthesis of 1,2,4-thiadiazoles from primary amides via thiolation and oxidative dimerization under solvent-free conditions: a greener approach

“…Its primary use involves replacing oxygen with sulfur in amides, resulting in the formation of thioamides, and also in ester functions. TBHP is a well-known oxidant 37 and has received much attention in many oxidation processes to form new C–C, C–N, C–O, C–S, and N–N bonds, 38 it is easily available, low cost, and easy to handle. 39 The solvent-free approach aligns with the principles of green chemistry, as they are eco-friendly and reduce pollution to quite an extent.…”