A microwave-assisted metal-free route to substituted 4-haloisoxazoles via decarboxylative halogenation of substituted isoxazole-4-carboxylic acids using N-iodosuccinimide (NIS) and N-bromosuccinimide (NBS) in the presence of K 3 PO 4 is described. It was discovered that the substitutions present at the 3-position of differently 3,5-disubstituted isoxazoles influenced the outcome of the protocol. The methodology is compatible for performing decarboxylative halogenation followed by decarboxylative Suzuki-Miyaura and Sonogashira couplings as one-pot process.
The decarboxylative/oxidative amidation of aryl α-ketocarboxylic acids with 5-aryl-3-nitroisoxazole-4-carboxylates and substituted dinitrobenzenes under oxidative aqueous conditions to afford N-aryl amides is described. The reaction is suggested to proceed via a radical pathway in which a benzoyl nitroxyl radical, the key intermediate formed from reaction between nitroarene and benzoyl radical from glyoxalic acid, couples with hydroxyl radical from water to produce amide. Mechanistic insight allowed the scope of the strategy to be expanded to the synthesis of amides via reaction between aryl α-ketocarboxylic acids and nitroso compounds.
A multicomponent reaction between isatin, tetrahydroisoquinoline,
and terminal alkyne in the presence of benzoic acid for the synthesis
of N-(substituted-2-(2-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinolin-3-yl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamides is described. This three-component reaction
proceeds via sequential formation of spirooxindole, generation of
isocyanate functionality via cleavage of the C2–C3 bond in
the isatin subunit of spirooxindole, and addition of the second molecule
of tetrahydroisoquinoline to the isocyanate group to offer title compounds.
Expansion of the protocol to four-component by including an additional
primary amine affords 1-substituted-3-(2-(2-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinolin-3-yl)phenyl)urea in low to moderate yields.
However, the reaction of intermediate spirooxindole with tetrahydroisoquinoline
or any primary or secondary amine produced the title compound in excellent
yields.
An efficient protocol for transforming alkyl 3‐nitro‐5‐(aryl/alkyl)isoxazole‐4‐carboxylates into 3‐amino‐ and 3‐hydrazinyl‐5‐aryl/alkyl‐isoxazole‐4‐carboxylates is described. The reaction that is carried out in aqueous acetonitrile solution generally afford the products without any chromatographic purification. Investigations with the substrate scope reveal that this protocol is compatible only when the ester group is present at the C‐4 position of the isoxazole ring.magnified image
tert‐Butyl hydroperoxide (TBHP) served as the methyl source under metal‐free aerobic conditions in the oxidative amination of the C(sp3)–H bond to synthesize quinazolin‐4(3H)‐ones and quinazolines from 2‐aminobenzamides and 2‐carbonyl‐substituted anilines, respectively.
A two-step
one-pot efficient synthesis of pyrido[2,3-
b
]indoles
via reaction between isatin, α-amino acid, and dipolarophile
has been developed. The initial 1,3-dipolar cycloaddition between
the reactants that is performed in the presence of either CuI or methanol
results in spirooxindoles that undergo POCl
3
-mediated intramolecular
dehydrative transformation to afford the title compounds.
A mild approach to diazenylation of active methylene compounds and N-heterocyclic compounds with arylhydrazine hydrochlorides in the presence of iodine under basic aerobic conditions was developed. The reaction could be executed either under heating or in the presence of blue LED light, though the latter condition was found to be relatively efficient. Presumably, the aryldiazene produced by oxidation of arylhydrazine hydrochloride acts as a nitrogen scavenger of the radical intermediate generated from the active methylene compound in the presence of iodine to produce the diazo compounds. The scope and limitations of the protocol are presented.
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