A Convenient Protocol for the Synthesis of Hindered Aryl Malononitriles

Abstract

A technically feasible method has been developed for the synthesis of variety of aryl malononitriles in high yields (70-95%) using the palladium-catalyzed coupling reaction of malononitrile with aryl bromides and chlorides, respectively. The influence a ­several reaction parameters such as base, ligand, solvent or tem­perature were investigated in some detail.

Key words

arylation - aryl malononitrile - C-C coupling reaction - Pd catalysis - oxopyrazoline herbicide

References and Notes

• 1a Cederbaum F, Brunner HG, and Boeger M. inventors; WO  9216510 A1.  ; Chem. Abstr. 1993, 118, 38935
• 1b Krueger BW, Fischer R, Bertram HJ, Bretschneider T, Boehm S, Krebs A, Schenke T, Santel HJ, and Luerssen K. inventors; DE  4109208.  ; Chem. Abstr. 1993, 118, 22227
• 1c Muehlebach M, Glock J, Maetzke T, and Stoller A. inventors; WO  9947525 A1.  ; Chem. Abstr. 1999, 131, 228720
• 1d Muehlebach M, Glock J, Maetzke T, and Stoller A. inventors; WO  2000047585A1.  ; Chem. Abstr. 2000, 133, 164053
• 1e Maetzke T, Mutti R, and Szczepanski H. inventors; WO  2000078881 A2.  ; Chem. Abstr. 2000, 134, 56699
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5

This method indeed worked well in our hands for the preparation of 2 using substrate 1b (58% yield), but failed completely when the technically more suitable bromide 1a was used.

9

Standard Experiment.
Malononitrile (181 mg, 2.75 mmol), t-BuONa (720 mg, 7.5 mmol) and xylene (13 mL) were stirred in a Schlenk tube under argon at r.t. for 1 h. Aryl halide (2.5 mmol) and a mixture of PdCl₂ (2.5 µmol) and PCy₃ (17.5 µmol) in xylene (2 mL) were added and the reaction mixture was stirred at the required temperature. For the experiments described in Table [2] , the product was extracted with NaOH solution and after acidification with HCl, was isolated by filtration. The ¹H NMR spectra of all products were in agreement with the proposed structures.