Syntheses of Coniferyl and Sinapyl Alcohols
J. Agric. Food Chem., Vol. 46, No. 5, 1998 1795
NaBH(OAc)3 was chosen for preparing coniferyl and
sinapyl alcohols, even though it is weaker in reactivity
than sodium monoacetoxyborohydride, because it is
commercially available and more easily prepared in situ
from NaBH4 that is already stocked in most laborato-
ries. Excess acetic acid does not replace the remaining
hydride, but excessive amounts are avoided here to
simplify the workup. Coniferaldehyde 1a and sinapal-
dehyde 1b were smoothly reduced to coniferyl alcohol
2a and sinapyl alcohol 2b by sodium triacetoxyborohy-
dride, generated in situ, in ethyl acetate with no
detectable 1,4-reduction product (Figure 1). The yields
were 97 and 92% for 2a and 2b, respectively. The same
selectivity was obtained with commercial NaBH(OAc)3,
although the reduction rate was slower in that case.
Addition of acetic acid accelerated the reduction without
impairing its selectivity. Coniferyl alcohol 2a was
crystallized from methylene chloride/petroleum ether in
70% yield. Multigram quantities of coniferyl alcohol and
sinapyl alcohol were prepared in the same way without
any difficulty, and coniferyl alcohol was easily crystal-
lized in 77% yield. Attempts to crystallize sinapyl
alcohol from methylene chloride/petroleum ether were
unsuccessful; although it can be done (Quideau and
Ralph, 1992), the low melting point makes crystalliza-
tion capricious. We and others have had this difficulty
in the past, and it is not indicative of less pure sinapyl
alcohol. Crude sinapyl alcohol was pure enough to be
used directly for making DHPs or other purposes.
The major advantages of this method are as follows:
(1) the reducing agent, sodium triacetoxyborohydride,
is either available from commercial sources or easily
generated from sodium borohydride and can be used
directly without requiring particular caution (users
should adhere to safety precautions described, for
example, in standard material safety datasheet infor-
mation; hydrogen gas is liberated when HOAc is added
to make the triacetoxyborohydride); (2) large scale
preparations can be easily accomplished by using this
method with similar results; and (3) the required
products are prepared in high yields without any 1,4-
reduction that produces the contaminant saturated
alcohols that have always existed in previously de-
scribed reductive methods.
F igu r e 1. Reduction of coniferaldehyde 1a and sinapaldehyde
1b. * The ratio was measured by GC; 3a ,b were undetectable
in products of NaBH(OAc)3 reductions.
g), after addition of coniferaldehyde 1a , the mixture was
stirred overnight (∼10 h) at room temperature. Workup as
above afforded crude 2a without any 1,4-reduction product
detectable by GC. Crystallization from CH2Cl2/petroleum
ether led to pure 2a as pale yellow plates in 77% yield.
Red u ction w ith Com m er cia l Sod iu m Tr ia cetoxybor o-
h yd r id e. The acetoxyborohydride reagent is available com-
mercially but seems to function more slowly than the in situ-
prepared reagent that is conveniently prepared as described
above. Commercial NaBH(OAc)3 (1.68 mmol, 3.0 equiv) was
suspended in ethyl acetate (15 mL), and coniferaldehyde 1a
(100 mg, 0.56 mmol) was added. The mixture was stirred
overnight when TLC showed that ∼40% of the starting
material remained. About 0.1 mL of acetic acid was added,
and stirring was continued for 6 h, at which time TLC showed
the reduction was done. Workup as above afforded crude 2a
(96 mg, 95%) without any 1,4-reduction product detectable by
GC. Adding acetic acid initially allows complete reduction
overnight.
Sin a p yl Alcoh ol 2b. (E)-Sinapaldehyde 1b (130 mg, 0.62
mmol) was reduced as described for 1a to yield crude (E)-
sinapyl alcohol 2b as a pale yellow syrup (120 mg, 91%).
Again, no dihydrosinapyl alcohol could be detected by NMR
or GC. For large scale preparation, sinapaldehyde 1b (5.0 g,
24.0 mmol) was reduced overnight as described for 1a to yield
crude sinapyl alcohol 2b as a pale yellow syrup (4.85 g, 96%).
Crystallization of sinapyl alcohol is difficult (Quideau and
Ralph, 1992). The product produced by using this method is
suitable for use without further purification.
RESULTS AND DISCUSSION
Sodium borohydride is a versatile and relatively mild
reducing agent generally used for the reduction of
aldehydes and ketones. However, reduction of conju-
gated aldehydes and ketones with sodium borohydride
is highly solvent dependent and generally does not
result in useful regioselectivity (Nutaitis and Bernardo,
1989). It is not surprising that coniferyl alcohol pre-
pared by sodium borohydride reduction of coniferalde-
hyde was contaminated with saturated coniferyl alcohol
(Ludley and Ralph, 1996). Furthermore, we were
unable to obtain the claimed selectivity using the
procedure in that paper. GC showed that ∼3% (not
<1%) levels of dihydroconiferyl alcohol 3a were obtained
when coniferaldehyde was reduced by sodium borohy-
dride in ethyl acetate (Figure 1).
Selective 1,2-reduction is usually achieved by the use
of modified hydride reagents, which are formed by
replacing hydride with bulky substituents or electron-
withdrawing groups. For example, sodium (mono- and
tri-)acetoxyborohydrides, prepared by adding controlled
amounts of acetic acid to sodium borohydride in a
solvent, reduced enones and enals in THF more selec-
tively than the parent sodium borohydride (Nutaitis and
Bernardo, 1989). NaBH(OAc)3 reduced aldehydes in the
presence of ketones (Gribble and Ferguson, 1975).
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