Non-Catalyzed Reductions With Formate Salts: Conversion of Nitroaromatic Compounds to the Corresponding Primary Amines

References

• March , J. 1977 . Advanced Organic Chemistry: Reactions, Mechanisms, and Structure , Second Edition , 1125 New York, N.Y. : McGraw‐Hill . For methods that have been developed to effect this transformation, see:
   Google Scholar
• Bar , R. and Sasson , Y. 1981 . Tetrahedron Lett. , 22 : 1709 and references therein
   Google Scholar
• Cortese , N. A. and Heck , R. F. 1977 . J. Org. Chem. , 42 : 3491 M.O. Terpko and R.F. Heck, J. Org. Chem. 45, 4992 (1980). Simultaneously another research group reported the reduction of nitro compounds with palladium catalysts and formic acid in the absence of a tertiary amine. See J.D. Entwistle, A.E. Jackson, R.A.W. Johnstone, and R.P. Telford, J. Chem. Soc., Perkin Trans. 1, 443 (1977)
   Web of Science ®Google Scholar
• Nanjo , K. , Suzuki , K. and Sekiya , M. 1976 . Chem. Lett. , : 1169 Chem. Pharm. Bull., 25, 2396 (1977)
   Google Scholar
• Moore , M. L. 1949 . Org. Reactions , 5 : 301 One of the earliest reports of the use of formic acid as a reducing agent involved the conversion of iminium salts to amines with ammonium formate (the Leuckart reaction). For a review of this useful reduction, see
   Google Scholar
• Among the suppliers of “anhydrous” formic acid are Fluka (purum anhydrous HCOOH, 98% min.) and Eastman Organic Chemicals (formic acid, 97% min.)
   Google Scholar
• NMR analysis of the crude reaction product verified the absence of the desired m‐toluidiine, yet also indicated that some type of transformation was occurring at the higher reaction temperature when this solvent was used. Nevertheless, the product mixture still consisted of >60% starting nitro compound
   Google Scholar
• This experiment was run by refluxing a mixture of 2 mmol of m‐nitrotoluene, 0.25 mL (6.64 mmol) of 98% formic acid, 1.2 mL (8.6 mmol) of triethylamine, and 4 mL of 1‐methy 1–2‐pyrrolidinone for 21 h
   Google Scholar
• The starting nitro compound was recovered in >95% yield from this experiment
   Google Scholar
• Although use of other dipolar aprotic solvents that enhance the nucleophilicity of formate ion might be possible for this reaction, use of DMF at reflux proved to be unsuccessful. Likewise, if the reaction mixture containing 1‐Methyl‐2‐pyrrolidinone as the solvent was heated in a bath at 155oC (vs. a reflux temperature of approximately 200oC) no reduction occurred after 21 hours
   Google Scholar
• No systematic study of the advantage of this or other buffers was attempted. If potassium phosphate monobasic was left out of this reaction mixture, reduction nevertheless occurred; however, the yield of m‐toluidine was greatly reduced (56% vs. 81%). Presumably the solvent or adventitious water present in it served as the proton donor in such an experiment
   Google Scholar
• All of these substrates are available from Aldrich Chemical Co., Milwaukee, WI., USA.
   Google Scholar
• Babler , J. H. and Sarussi , S. J. 1981 . J. Org. Chem. , : 46 For more details about this transformation, including a survey of the reduction of several other representative carbonyl compounds with sodium formate, see, in press
   Google Scholar
• In an experiment involving p‐nitrophenyl n‐butyl ether, the reduction was effectively stopped by a large increase in the amount of KH2PO4 (10.0 vs. 3.7 mmol) used as a buffer
   Google Scholar