(467f) Sustainable and Continuous Reduction of Amides

Sustainable
and Continuous Reduction of Amides

Kathryn
Rix, Geoff Kelsall, Mimi Hii, Klaus Hellgardt

Amines
are important organic intermediates for the chemical industry; used in the
production of agrochemicals, dyes, pharmaceuticals, surfactants and plastics.
Amines constitute important core structures of many biologically active
molecules, and are particularly prevalent in central nervous system (CNS) drugs,
which make up the largest sector of pharmaceuticals sold worldwide.

The
reduction of amides to amines can be effected electrochemically by a route
summarised below:

Cathode:                    R-CONH₂
+ 4H⁺ + 4e^{-    reduction}    R-CH₂NH₂
+ H₂O         (1.0)

Nafion membrane:   H⁺
(anolyte)                                 H⁺ (catholyte)                 (1.1)

Anode:                       2H₂O
                           ^oxidation      O₂ + 4H⁺ +
4e^-                        (1.2)

Overall reaction:       R-CONH₂
+ H₂O                          R-CH₂NH₂ + O₂      
      (1.3)

An
electrochemical flow-cell reactor has been constructed using boron doped
diamond cathodes (BDD) to reduce a range of amides, demonstrating chemo-selectivity,
stereo-selectivity and product selectivity by forming the corresponding amine.

For
example, maleimide was selectively reduced to succinimide rather than to the
corresponding amine, demonstrating chemoselectivity. This was developed further
to show that the cyclic double bond can be preferentially reduced over an allyl
group.

A
conversion of >99% and a current efficiency of 96% were achieved. After
neutralisation and extraction, ¹H NMR indicated that the cyclic double
bond had been reduced while the allyl group remained intact (Figure 1). As the cyclic
double bond is more electron deficient, the addition of two electrons and two
protons is more favourable than addition to the allyl group.

Figure
1: Electrochemical reduction of N-allylmaleimide

In
this presentation we will discuss further examples of the facile continuous electrochemical
reduction of amides, avoiding the use of hydride agents.