Development of CN Coupling Using Mechanochemistry: Catalytic Coupling of Arylsulfonamides and Carbodiimides

Abstract

Reported herein is the mechanochemical synthesis of sulfonyl guanidines, a family of molecules which are relevant as pharmaceuticals and herbicides, by direct coupling of sulfonamides and aromatic or aliphatic carbodiimides. Attempts to conduct the coupling in solution have either failed or given very low conversions, thus demonstrating mechanochemistry as the necessary component for the discovery of this synthetic strategy.

Mechanochemical Synthesis of Phosphazane‐Based Frameworks

“…[12,13] In its broadest terms, mechanochemistrydates back two millennia; [14] however,o nly in recent decadesh as it experienced ar enaissance. [18][19][20][21][22][23][24][25][26] Despite its long history and recents uccesses, these methodologies remain largely unexploredf or the synthesis of main-group compounds, with only works by Peters et al [27] andH anusa et al [22,28] on organometallic complexes.W er ecently reported af ast and high-yielding, multi-step, orthogonal mechanochemicals ynthesis of indium(III)c omplexes, [29] and demonstrated the value of this technique in enabling the isomerisation of as terically encumbered phosphazane. [18][19][20][21][22][23][24][25][26] Despite its long history and recents uccesses, these methodologies remain largely unexploredf or the synthesis of main-group compounds, with only works by Peters et al [27] andH anusa et al [22,28] on organometallic complexes.W er ecently reported af ast and high-yielding, multi-step, orthogonal mechanochemicals ynthesis of indium(III)c omplexes, [29] and demonstrated the value of this technique in enabling the isomerisation of as terically encumbered phosphazane.…”

Organic Synthesis without Conventional Solvents

“…Whereas conventional methods require drying of the solvent and an inert atmosphere, ball milling allows the reaction to be performed in an aerobic environment. [29] Scheme 4. An example is the dimerization of fullerene (C 60 ) by milling with 20 equiv.…”

Metal-catalyzed organic reactions using mechanochemistry

“…Highlighting the potential of mechanochemistry for the discovery of previoulsy not known reaction pathways, the mechanochemical copper-catalyzed coupling was subsequently applied for the first one-step synthesis of sulfonylguanidines from sulfonamides and carbodiimide nucleophiles (Scheme 6). 66 readily yields sulfonylguanidines upon catalyst-free milling with alkyl-substituted carbodiimides, the use of aryl-substituted carbodiimides or arylsulfonamides was enabled only by catalytic CuCl under LAG conditions, affording a gallery of sulfonyl guanidines in excellent yields. Again, the product separation was achieved by simply milling the reaction mixture with aqueous EDTA, followed by washing with water.…”

“…It is, therefore, clear that the solvent-intense methodologies for product isolation by recrystallization and chromatography remain highly popular, effectively diminishing the environmentally-friendly value of a catalytic, solvent-free reaction. Such state of affairs may be gradually changing, based on recent reports 62, 64,66 in which product purification is achieved by washing with water and/or minimum amounts of organic solvent. Sublimation may hold particular promise in that context, and was recently investigated as a completely solvent-free method for product isolation in mechanochemical organic and organometallic reactions.…”