Abstract:Abstract:The reaction of 4-hydroxycoumarin (1) with some primary amines 2a-h and morpholine (2i) under microwave irradiation occurred without opening of the lactone ring to give N-substituted 4-aminocoumarins 3a-i in excellent yields. Under the same experimental conditions, 4-hydroxy-6-methyl-2-pyrone (4) reacted with benzylamine (2e) or 2-phenylethylamine (2f) to give the corresponding N,N'-disubstituted 4-amino-6-methyl-2-pyridones 5e,f. The main advantages of this procedure are dramatically shortened reacti… Show more
“…Moreover, the hydroxyl group can be selectively replaced by the amino group of primary and secondary amines, as illustrated in the syntheses of compounds 36 and 37 under previously reported conditions. [27] It is worth mentioning that 4-aminocoumarins exhibit outstanding bioactivities. [28] Finally, the reaction of 5 with POCl3 furnished 4-chlorocoumarin 38 in excellent yield.…”
Direct and selective C(sp 2 )-H/C(sp 2 )-H crossdehydrogenative coupling has become a promising strategy to increase molecular complexity with a high atom economy. This study describes an efficient and straightforward protocol for the regioselective C3-H/C3-H cross-coupling of 4-hydroxycoumarin derivatives with quinoxalin-2(1H)-ones, including late-stage modification of natural drugs, promoted by visible light under aerobic conditions at room temperature. With this approach, a wide range of hybrid drug-like molecules were prepared, using air as the terminal oxidant. Remarkably, the C4-OH group at the coumarin ring is essential for the reaction and has been used as a handle for diverse functionalizations of the final products. Moreover, sunlight can promote the reaction under very mild and sustainable conditions, even on a gram scale. Qualitative and semi-quantitative tools were used to demonstrate the greenness advance of this methodology over previously reported ones. Several experiments were conducted to propose a plausible mechanism for this transformation.
“…Moreover, the hydroxyl group can be selectively replaced by the amino group of primary and secondary amines, as illustrated in the syntheses of compounds 36 and 37 under previously reported conditions. [27] It is worth mentioning that 4-aminocoumarins exhibit outstanding bioactivities. [28] Finally, the reaction of 5 with POCl3 furnished 4-chlorocoumarin 38 in excellent yield.…”
Direct and selective C(sp 2 )-H/C(sp 2 )-H crossdehydrogenative coupling has become a promising strategy to increase molecular complexity with a high atom economy. This study describes an efficient and straightforward protocol for the regioselective C3-H/C3-H cross-coupling of 4-hydroxycoumarin derivatives with quinoxalin-2(1H)-ones, including late-stage modification of natural drugs, promoted by visible light under aerobic conditions at room temperature. With this approach, a wide range of hybrid drug-like molecules were prepared, using air as the terminal oxidant. Remarkably, the C4-OH group at the coumarin ring is essential for the reaction and has been used as a handle for diverse functionalizations of the final products. Moreover, sunlight can promote the reaction under very mild and sustainable conditions, even on a gram scale. Qualitative and semi-quantitative tools were used to demonstrate the greenness advance of this methodology over previously reported ones. Several experiments were conducted to propose a plausible mechanism for this transformation.
“…In solution, the likely tautomeric forms of 4-hydroxycoumarin are 2‑hydroxy‑4-chromenone (A) and 2, 4-chromandione (B) [28] . Indeed, synthesis of L TA is carried out via nucleophilic attack of NH 2 group of 3-picolylamine on the C10 carbonyl of 2, 4-chromandione with elimination of water molecule [ 29 , 30 ], according to the following detailed mechanism: Scheme 1 Synthesis mechanism of ligand (L TA ). …”
Highlights
New coumarin derivative (4-[(
pyridin
-3-
ylmethyl
)
amino
]−2
H
-chromen-2-one) (L
TA
) was synthesized and characterized by spectroscopic techniques.
The ligand was characterized by single-crystal X-ray diffraction method and optimized by DFT method.
The chemical reactivity, kinetic and thermodynamic parameters of L
TA
were calculated.
The interaction of L
TA
with SARS-CoV-2/Main protease (Mpro) was studied.
The docking simulation showed active L
TA
molecule with the ability to inhibit SARS-CoV-2.
“…4 In the study of the reaction of 3 acetyl 4 hydroxy coumarin 2 with benzylamine 4a, we found that the reac tion pathway depends on the solvent nature and the reac tion time. For instance, coumarin 2 reacted with benzyl amine in acetonitrile at room temperature, giving salt 7 in 0.5 h (Scheme 2, path b), which is analogous to salt 5 (see Scheme 1).…”
mentioning
confidence: 99%
“…Opening of the α pyrone ring into 3 hydroxy 3 (2 hydroxyphenyl)prop 2 enamides is also possible. 4 It is also known 5 that primary amines react with 3 acetyl 4 hydroxycoumarin at its acetyl substituent. Modification of fluorine containing 4 hydroxycoumarins have not been studied hitherto.…”
mentioning
confidence: 99%
“…These compounds have been studied 3 only in reactions with ammonia and morpholine, the major process in these transformations being aromatic nucleophilic substitution for the F atoms at the position C (7). 4 Hydroxycoumarins are known to react with primary and secondary amines at the OH group to give N substituted 4 aminocoumarins. Opening of the α pyrone ring into 3 hydroxy 3 (2 hydroxyphenyl)prop 2 enamides is also possible.…”
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