Simple and Efficient One-Step Conversion of Benzonitrile into Methylarene under Mild Conditions

Abstract

A very simple and efficient method has been developed for the synthesis of various methylarenes from the corresponding benzonitriles under mild conditions. The protocol uses Pearlman’s catalyst to achieve the transformation under an atmosphere of gaseous hydrogen and proceeds smoothly in many common solvents. A series of methylarenes were thus obtained in high yields and purities.

reduction - nitriles - palladium - methylarene - Pearlman’s catalyst

References and Notes

1 Rappoport Z. In The Chemistry of the Cyano Group   Interscience Publishers; London: 1970. 

2 Larock RC. In Comprehensive Organic Transformations: A Guide to Functional Group Preparation   VCH Publishers; New York: 1989.  p.42 

3 Andrade JG. Maier WF. Zapp L. Schleyer PvR. Synthesis  1980,  802 

4 Kindler K. Lührs K. Liebigs Ann. Chem.  1967,  707:  26 

5 Brown GR. Foubister AJ. Synthesis  1982,  1036 

6 Bérubé M. Poirier D. Can. J. Chem.  2009,  87:  1180 

7 Laplante Y. Cadot C. Fournier M.-A. Poirier D. Bioorg. Med. Chem.  2008,  16:  1849 

8 Poirier D. Boivin RP. Tremblay MR. Bérubé M. Qiu W. Lin S.-X. J. Med. Chem.  2005,  48:  8134 

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Typical Experimental Procedure for the Reduction of Benzonitrile to Methylarene
To a stirred solution of benzonitrile (0.15 mmol) in solvent (4 mL) was added Pd(OH)₂/C [20 mol%, ≤50% wet, 20 mg (19 mol%) or 40 mg (38 mol%)]. The mixture was stirred at ambient temperature under 1 atm of hydrogen for 3-18 h. The catalyst was removed by filtration through a short pad of Celite and washed with EtOAc. The solvent was removed under reduced pressure to afford the reduced product.

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Optimized conditions use MeOH as solvent, 19 mol% of Pearlman’s catalyst [20% Pd(OH)₂/C], 1 atm of gaseous H₂ and 3 h of stirring at r.t. When the reaction was done on a larger scale, anhyd MeOH was used, and the organic layer was dried using MgSO₄.