An expeditious and environmentally friendly synthesis of 3-substituted isocoumarins using microwave irradiation

Abstract

A microwave-assisted, environmentally friendly, high-yielding, time-saving synthesis of medicinally important 3-substituted isocoumarins was carried out in a single step by direct condensation of homophthalic acid with aryol and acyl chlorides under solvent-free conditions without any solid support. The synthesised isocoumarins were structurally characterised by microanalysis, 1H NMR, EI, IR and UV.

Synthesis of 3-Substituted Isocoumarins via a Cascade Intramolecular Ullmann-Type Coupling–Rearrangement Process

“…The wide range of biological activities has led to continued interest in the synthesis of isocoumarin derivatives, especially isocoumarins substituted in the 3-position. Various methods for constructing these molecules have been reported, including cyclization of 2-alkenyl or 2-allylbenzoic acid derivatives, condensation of benzoic acid derivatives with alkynes or alkenes, palladium-catalyzed carbonylation of o -iodobenzyl alkyl ketones or α-( o -haloaryl)-substituted ketones, microwave-assisted reaction of homophthalic acid with acid chlorides or esters, NHC-catalyzed oxidative cyclization of 2-alkynyl benzaldehydes, and thermal cyclization reaction of δ-ketoamides . These methods were presented as efficient protocols for both carbon and heterocycle assembly.…”

One-Step Synthesis of Isocoumarins and 3-Benzylidenephthalides via Ligandless Pd-Catalyzed Oxidative Coupling of Benzoic Acids and Vinylarenes

“…For instance, Youn recently reported the oxidative cyclization of 2-alkynylbenzaldehyde catalyzed by N -heterocyclic carbene (Scheme a) . Synthetic methods avoiding alkyne-based substrates have also been developed, including cyclization of 2-alkenyl or 2-allylbenzoic acid derivatives, ,, microwave-assisted reaction of homophthalic acid with acid chlorides or esters, Cu(I)-catalyzed intramolecular sequential C–C coupling and rearrangement of 1-(2-halophenyl)-1,3-diones, and Cu(I)-catalyzed intermolecular domino reactions from 2-halobenzoic acids or 2-halobenzoic acid derivatives with 1,3-diketones. − Despite the efficiency of these synthetic strategies for isocoumarins, they are significantly limited by substrate availability. Most often, these methods involve multistep sequences, harsh conditions, or expensive catalysts and ligands.…”

Long-Range Olefin Isomerization Catalyzed by Palladium(0) Nanoparticles

“…We applied the Pd-catalyzed isomerization reaction to synthesize dihydroisocoumarin 33, a natural product isolated from brown alga Caulocystis cephalornithos that showed antiinflammatory activity (Scheme 4). 23 Starting with commercially available 2-hydroxy-6-methylbenzoic acid (34), substrate 36 was prepared after protection of the hydroxyl group and allylation with (E)-1-bromododec-2-ene. 24 The reaction of 36 and PdCl 2 in methanol afforded oxidized isocoumarin 38 in 98% yield, which should be derived from isomerized intermediate 37 undergoing spontaneous oxidative cyclization.…”

“…1 H NMR (CDCl 3 , 300 MHz) δ 0.85 (t, J = 7.1 Hz, 3H), 1.23 (br, 17H), 1.92−1.94 (m, 2H), 2.07−2.11 (m, 2H), 3.76 (q, J = 7.1 Hz, 2H), 5.30−5.44 (q, 2H), 5.56 (s, 2H), 6.69 (d, J = 7.5 Hz, 1H), 6.81 (d, J = 8.2 Hz, 1H); 7.27 (dd, J = 8.2 Hz, J = 7.5 Hz, 1H); 13 8-Hydroxy-3-undecyl-1H-2-benzopyran-1-one (38). 34 Palladium chloride (1.7 mg, 9 μmol) was added to a solution of compound 36 (36.0 mg, 0.090 mmol), 2,6-di-tert-butyl-4methylphenol (21 mg, 0.09 mmol), and methanol (5 mL). The suspension was stirred at rt for 5 h under an atmosphere of nitrogen and concentrated.…”