Oxidation and Reduction by Solid Oxidants and Reducing Agents using Ball-Milling - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 78

RCH CH CH 2 OH

R

100%

+0.25NaBH 4 ; ball milling

H

RCH 2 CH 2 CH 2 OH

O

R = Me, Ph

Scheme 3.24 Regiospecific reduction of a,b-unsaturated aldehydes by solvent-free
stoichiometric ball milling with NaBH 4 .

(68-98%)

CN

CH 2 (CN) 2 (1 eq)

CHO

CN

EtOOC COOEt

EtOOC COOEt

R

m.m. (30 Hz)
r.t.; 90 min

H N

R

N

(1 eq)

p -toluidine (1 eq)
ZnCl 2 (25 mol%)

R

R = H, Cl, Br, NO 2 , N(CH 3 ) 2

(62-98%)

Scheme 3.25 Direct reductive benzylization of malononitrile and 4-methylaniline
(p-toluidine) using a 1,4-dihydropyridine (HEH).

Blanchard et al. have analyzed the reduction reaction of VCl 3 and LiAlD 4
at varying ball-mill energies (from 400 to 720 rpm). VCl 3 was reduced by
the formation of Li-V-Cl metastable phases, LiCl and free Al and V or Al-V
phases, from low to high ball-milling energies. Measurements of the
hydrogen released were made using Sievert's apparatus as well as X-ray and
neutron diffraction experiments that helped the authors to demonstrate
that kinetics enhancement reaches a limit with increased ball-mill energy.
They reported that even under mild conditions, at or close to room
temperature, the two first steps of the decomposition of VCl 3 -enhanced
LiAlD 4 occurs during the first weeks after milling at temperatures in the
range 20-50 1C. 30
The direct reductive benzylization of malononitrile and 4-methylaniline
using aromatic aldehydes was achieved by Wang et al. using Hantzsch 1,4-
dihydropyridine (HEH) as the only organo-reductant, under solvent-free
one-pot mechanochemical conditions (Scheme 3.25). The benzylidenema-
lononitriles and imines formed in situ were e ciently reduced to give ben-
zylated malononitriles and anilines in 62-98% yields at 30 Hz after 90 min
milling (Retsch MM200 mixer mill, Retsch GmbH, Haan, Germany). Fur-
thermore, the HEH organo-reductant demonstrates complete selectivity, as
no reduction of any other functional group such as aldehydes, nitro or cyano
groups was observed. 31

3.4 Conclusion
This chapter provides a comprehensive overview of solvent-free mechano-
chemical procedures for oxidation/reduction steps in the synthesis of fine