3-Methylene-2,4-chromandione in situ trapping: introducing molecular diversity on 4-hydroxycoumarin

Abstract

3-Methylene-2,4-chromandione trapped in a solid-state stable Mannich adduct, is released in solution.

Catalyst-Free One-Pot Three-Component Synthesis of 4-Hydroxy-3-pyrazolylcoumarins in Ethanol at Room Temperature: Enolisable Aroylhydrazones as Efficient Ambident Nucleophile

“…In quest of a green methodology we started our optimization study toward the synthesis of 4-hydroxy-3-pyrazolylcoumarin derivatives ( 4 ) by choosing the reaction of p -methoxyphenylglyoxal ( 1 , 1.0 mmol), 4-hydroxycoumarin ( 2 , 1.0 mmol), and ( E )-2-(2-phenylhydrazono)-1-( p -tolyl)­ethan-1-one ( 3 , 1.0 mmol) as the model reaction (Table ). The synthesis followed a one-pot two-step process at room temperature (25–30 °C) where first there was initial stirring of a mixture of arylglyoxal ( 1 ) and 4-hydroxycoumarin ( 2 ) which produced a non-isolable chalcone type intermediate − through condensation (detected by LC-MS, Supporting Information), and then after 30 min, aroylhydrazone ( 3 ) was added to the same reaction mixture for further reaction to generate the final product 4 . At the beginning the reactions were carried out without adding any solvent or catalyst, but no product was formed even after prolong stirring for 12 h in neat conditions (Table , entry 1).…”

“…The formation of different products 4 and 6 from similar reactants and reaction conditions was surprising but can be rationalized on the basis of a mechanism as described in Scheme . Initially arylglyoxal 1 undergoes Claisen–Schmidt condensation with 4-hydroxycoumarin 2 to produce chalcone intermediate A − ­(detected by LC-MS, Supporting Information), which serves as an electrophilic acceptor at the CC bond. Next, nucleophilic attack of the enolic form of aroylhydrazone 3 at the olefinic carbon of A produces Michael adduct B which on rearrangement furnishes hydrazones C .…”

One-Pot Reductive Alkylation of 2,4-Dihydroxy Quinolines and Pyridines

“…14: mp 87−89 °C; 1 H NMR (500 MHz, chloroform-d) δ 8.12 (d, J = 5.6 Hz, 1H), 7.07 (d, J = 7.7 Hz, 2H), 7.01 (d, J = 8.1 Hz, 2H), 6.80 (d, J = 5.6 Hz, 1H), 4.16 (s, 2H), 2.73 (s, 6H), 2.30 (s, 3H); 13 C{ 1 H} NMR (126 MHz,154.5,147.7,135.6,135.5,129.1,127.8,124.9,112.4,43.7,34.7,21. 13: 1 H NMR (500 MHz, chloroform-d) δ 8.09 (d, J = 5.3 Hz, 1H), 7.07 (d, J = 7.6 Hz, 2H), 7.01 (d, J = 7.9 Hz, 2H), 6.94 (d, J = 5.3 Hz, 1H), 4.17 (s, 2H), 2.77 (s, 6H), 2.31 (s, 3H); 13 C{ 1 H} NMR (126 MHz,146.3,145.8,135.8,135.5,129.1,127.7,124.5,118.6,42.9,34.4,21.0 (15). To a reaction vial containing 2,4-dichloro-3-(4-methylbenzyl)quinoline (8b) (100 mg, 0.3 mmol, 1 equiv), zinc cyanide (19 mg, 0.2 mmol, 0.5 equiv), and tetrakis(triphenylphosphine)palladium (38 mg, 0.03 mmol, 0.1 equiv) was added degassed DMF (1 mL) and the resulting suspension was allowed to stir at 115 °C using a heating block fitted on a stir plate for 2 h. Once complete, the reaction was concentrated and purified by column chromatography using ethyl acetate in hexanes as the mobile phase to give 15 as a white solid (85 mg, 88%).…”

“…13 However, these reports are limited to aliphatic activated methylene-containing scaffolds such as Meldrum's acid, malononitrile, ethyl 2cyanoacetate, and 2-(4-nitrophenyl)acetonitrile. 13 Alternatively, methods reported by Borbeĺy et al 14 and Popowycz et al 15 utilize triethyl amine formic acid and a two-step method for C-3 alkylation of 2,4-dihydroxyquinoline to yield the coupled products, respectively. Herein, we report a simple, scalable method to construct 3-substituted quinolines by coupling of 2,6-dihydroxy quinolines and aldehydes through a condensation−reduction sequence employing the Hantzsch ester as a mild hydride source.…”

Metal Free C–H Functionalization Enabled Diastereoselective Multicomponent Reaction of N-Heterocycles to Fused Heteropolycycles

“…Therefore, the known examples of metal and oxidant free difunctionalization either make use of prefunctionalized starting material or have a narrow substrate scope. The classical multicomponent reaction of N-heterocycles with aldehyde and hydroxycoumarin provides α-benzylamino coumarins (Scheme , eq 1) . Herein, we report an unprecedented C–H functionalization enabled diastereoselective multicomponent reactions of N-heterocycles to fused heteropolycycles under metal and oxidant free conditions.…”