This document summarizes studies on the cobalt boride-mediated reduction of nitriles to alcohols or amines. Key findings include: 1) Cobalt boride was found to selectively reduce benzonitrile to benzyl alcohol under mild conditions in water, compatible with several functional groups. 2) Reaction conditions were optimized in water to give high yields of alcohols from aromatic nitriles. 3) Future work will explore the substrate scope and investigate conditions for selective reduction of nitriles to primary amines.

1. Background
Studies of Cobalt Boride-Mediated Nitrile Reductions
Michael DeBrota and Jason J. Pflueger*
Rose-Hulman Institute of Technology, Terre Haute, Indiana
Optimization in Water Functional Group Compatibility
Conclusions
Acknowledgements
Solvent Screen
Other Parameters
• The nitrile is a versatile and robust functional group
• Nitrile reduction to the corresponding amine generally requires harsh
conditions with poor functional group tolerance (typically LiAlH4 or high
pressures of H2 gas)
• Satoh and coworkers reported the combination of cobalt(II) chloride and
sodium borohydride as an effective reducing agent for nitriles, nitro groups,
and amides1
• Ganem and coworkers isolated the cobalt boride (Co2B) formed in this
reaction and found borane tert-butylamine (BH3•tBuNH2) to be an effective
external reductant2
• These initial studies suggested possible selectivity for nitriles in the
presence of amides, esters, and alkenes with minimal follow-up work
performed
• Despite the broad synthetic potential for this reduction protocol, there has
only been one recent application in organic synthesis3
Goal: Develop a convenient, selective, high-yielding, functional group- tolerant
nitrile reduction protocol using cobalt boride
Future Directions
RHIT Department of Chemistry and Biochemistry
James (Lou) Johnson – Instrument Manager
Michelle Sharp – Stockroom Manager
Rose-Hulman Summer Undergraduate Research Fellowship (R-SURF)
Eli Lilly Undergraduate Research Grant
• Achieved mild and selective reduction of benzonitrile to benzyl alcohol
mediated by cobalt boride
• Water, a green solvent, used for both cobalt boride preparation and nitrile
reduction
• Cobalt boride showed no catalytic activity in this reaction
• Conditions compatible with several common functional groups
• Complete optimization of reaction conditions in water to produce alcohols
• Explore scope of aromatic nitrile substrates (electronics, substitution pattern,
functional group tolerance, presence of heteroatoms)
• Expand reaction conditions to aliphatic nitrile reduction
• Investigate conditions for selective reduction to the corresponding primary
amine (aromatic, heteroaromatic, and aliphatic nitriles)
1) Satoh, T.; Suzuki, S.; Suzuki, Y.; Miyaji, Y.; Imai, Z. Tetrahedron Lett. 1969, 52, 4555-4558.
2) Heinzman, S. W.; Ganem, B. J. Am. Chem. Soc. 1982, 104, 6801-6802.
3) Kou, K. G. M.; Pflueger, J. J.; Kiho, T.; Morrill, L. C.; Fisher, E. L.; Clagg, K.; Lebold, T. P.; Kisunzu, J. K.;
Sarpong, R. J. Am. Chem. Soc. 2018, 140, 8105-8109.
• Protic solvents were the most effective, although some conversion was
observed in toluene at 100 °C
• THF mixtures with MeOH or H2O show promise for broader substrate
solubility
• The reaction also proceeded fully in pure water, producing a significant
amount of benzyl alcohol
• Potential for 1-step green alcohol synthesis from nitriles
Screening Alternative Reducing Agents
Assessing Catalytic Activity of Co2B
• Decreasing concentration led to increased proportion of alcohol
• Changing drying agent to Na2SO4 prevented protonation of amine product
• Decreasing equivalents of BH3•tBuNH2 greatly improved selectivity for
benzyl alcohol formation