Synthesis and pharmacological properties of 4-guanidinomethyl- and 4-(N′-phenylamidino) quinolines

Vasil'eva, V. F.; Medvedev, B. A.; Galitsina, V. A.; Korsakova, I. Ya.; Shvedov, V. I.; Mashkovskii, M. D.

doi:10.1007/bf00765592

Cited by 1 publication

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“…The reduction of arylacetonitriles lacking fluorine substitution at the benzylic position also often requires high temperatures or catalysts to proceed; the addition of LAH to benzyl nitrile under analogous conditions for 5d formed no reduced product. 49,50 Cyclization reactions to form products analogous to benzothiazole 5i without fluorine atoms did not proceed under analogous conditions, even with the addition of AlCl 3 as Lewis acid. 51−53 We ascribe the demonstrated difference in reactivity between aryldifluoroacetonitriles and arylacetonitriles to the inductive effect of the fluorine atoms adjacent to the nitrile carbon.…”

Section: Functionalization Of the Coupled Productsmentioning

confidence: 99%

Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF₂CN

Nicolai,

Fantoni,

Butcher

et al. 2024

J. Am. Chem. Soc.

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Molecules bearing fluorine are increasingly prevalent in pharmaceuticals, agrochemicals, and functional materials. The cyanodifluoromethyl group is unique because its size is closer than that of any other substituted difluoromethyl group to the size of the trifluoromethyl group, but its electronic properties are distinct from those of the trifluoromethyl group. In addition, the presence of the cyano group provides synthetic entry to a wide range of substituted difluoromethyl groups. However, the synthesis of cyanodifluoromethyl compounds requires multiple steps, highly reactive reagents (such as DAST, NSFI, or IF5), or specialized starting materials (such as α,α-dichloroacetonitriles or α-mercaptoacetonitriles). Herein, we report a copper-mediated cyanodifluoromethylation of aryl and heteroaryl iodides and activated aryl and heteroaryl bromides with TMSCF2CN. This cyanodifluoromethylation tolerates an array of functional groups, is applicable to late-stage functionalization of complex molecules, yields analogues of FDA-approved pharmaceuticals and fine chemicals, and enables the synthesis of a range of complex molecules bearing a difluoromethylene unit by transformations of the electron-poor CN unit. Calculations of selected steps of the reaction mechanism by Density Functional Theory indicate that the barriers for both the oxidative addition of iodobenzene to [(DMF)CuCF2CN] and the reductive elimination of the fluoroalkyl product from the fluoroalkyl copper intermediate lie in between those of [(DMF)CuCF3] and [(DMF)CuCF2C(O)NMe2].

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Section: Functionalization Of the Coupled Productsmentioning

confidence: 99%

Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF₂CN

Nicolai,

Fantoni,

Butcher

et al. 2024

J. Am. Chem. Soc.

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show abstract

Synthesis and pharmacological properties of 4-guanidinomethyl- and 4-(N′-phenylamidino) quinolines

Cited by 1 publication

References 5 publications

Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF₂CN

Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF₂CN

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Synthesis and pharmacological properties of 4-guanidinomethyl- and 4-(N′-phenylamidino) quinolines

Cited by 1 publication

References 5 publications

Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF2CN

Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF2CN

Contact Info

Product

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Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF₂CN

Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF₂CN