VenPure® solution - The Dow Chemical Company

O
1 NaBH4, 1 LiCl
R
diglyme, 162 o C
OH
H
R Time Yield
Me 5 85
i Pr 5 83
t-Amyl 5 0
Mita, N.; Nagase, H.; Iizuka, H.; Oguchi, T.; Sakai, K.;
Horikomi, K.; Miwa, T.; Takahashi, S. EP 0839805; 1998
3. Assistance from Protic Solvents.
When sodium borohydride is dissolved in a protic solvent,
it will react with the solvent according to the equation
NaBH4 + x HOR � NaBHx(OR)4-x + x H2
The resulting borohydride derivative, NaBHx(OR)4-x, is a
stronger reductant than neat NaBH4 (this is due to
electron-donation from the oxygen ligands).
The art of using this technology resides in finding the
optimum reaction conditions that allow for the formation
of the strongly reducing borohydride derivative, without
loosing all of the hydrides to solvolysis. Indeed, if all 4
hydrides react with the protic solvent, then NaB(OR)4 is
formed, which has ZERO reducing strength :
NaBH4 + 4 HOR � NaB(OR)4 + 4 H2
Methanol is by far the most efficient solvent in enhancing
borohydride’s reductive strength. Water and ethanol are
second best, however, water is typically not a good solvent
for (longer chain) esters.
Ethanol would be a good solvent, however NaBH4 only
dissolves up to 4% in it. If one wants to use e.g. a 10%
NaBH4 dispersion in ethanol, then we recommend the use
of Rohm and Haas’ VenPure SF powder, which has a
small particle size (increased active surface).
The solubility of NaBH4 in water and methanol is higher
than 15%. Hence, for making large quantities of a NaBH4
solution in these 2 solvents, we recommend to use an
easier-to-handle, larger particle size, such as provided by
VenPure SF granules or VenPure AF caplets.
VenPure SF powder VenPure SF granules Venpure AF caplets
H
Hereunder are some examples of the use of protic solvents
for enhancing Borohydride’s Reducing Strength.
A. Mixture : Water / Dioxane 15
O
Me
R O
7-10 hydride eq NaBH 4
Water or Water/Dioxane,
RT, 2-24 h
R O H
Substrate Time(h) Yield
PhCO2Me 12 80
2-ClPhCO2Me 6 100
2-NO2PhCO2Me 2 100
2-MePhCO2Me 12 80
2-MeOPhCO2Me 24 60
Bianco, A.; Passacantilli, P.; Righi, G. Synth. Commun. 1988, 18, 1765
B. Mixture : an organic solvent / methanol 16
MeO
O
OH OH
NaBH4 OMe
O
US 6,479,714 B1, Nov 12, 2002
Solvent, MeOH
RT
OH
Solvent Temp Time Ratio Yield
(°C) Sub /NaBH4 %
THF/MeOH 65 1h 1 / 3.5 99
THF/MeOH 68 2.5 1 / 1.8 95
Spirits/MeOH 0 22h 1 / 1.79 100
THF/ i PrOH 50 6h 1 / 1.8 85
iPrOH 50 7h 1 / 1.80 85
THF 25 17h 1 / 1.80 90
This technique is often used on larger-scale, as it is a
compromise between using the solubility characteristics of
THF, and the Reductive Strength Enhancing capability of
methanol.
C. Ethanol
In the above two examples the reactive protic solvent,
methanol or water, is diluted with a non-reactive solvent
This is done in order to minimize the amount of sodium
borohydride that is lost due to solvolysis decomposition. In
some instances, a 2-solvent system may not be optimal. It
is then possible to replace it by one protic solvent that
decomposes NaBH4 less rapidly. Ethanol 17 and
polyethylene glycol 18 are such solvents. They have the
advantage that borohydride’s solvolysis rate is
substantially slower then in methanol. On the other hand,
their enhancing effect will be less pronounced.
.
OH