the reduction produces rearranged phenols,4 which do not
generate liquid crystalline monomers and polymers.4 The
rearranged phenols are evidently generated by intramolecular
transesterification of the intermediate benzyl alkoxide via a
six-membered endo-trig cyclic transition state,9 with loss of
phenoxide since it is the better leaving group (Scheme 2).
produces approximately 71% of the rearranged phenol in
addition to only 28% of the desired benzyl alcohol. As
expected, the low conversion of aldehyde in entries 2 and 3
demonstrates that HCl (aq pKa ) -7) reacts with NaBH4
rather than quench the intermediate benzyl alkoxide. Both
the low conversion of aldehyde and the lack of acrylate
formation in entry 4 demonstrates that acryloyl chloride also
reacts more rapidly than the benzaldehyde with NaBH4 and
is therefore consumed before it quenches the intermediate
benzyl alkoxide. Since only 2 equiv of acryloyl chloride were
used, 2 equiv of hydride were still available to reduce the
resulting aldehyde and benzaldehyde groups.
Scheme 2
In contrast, the benzaldehyde reduction proceeds to
approximately 90% conversion in the presence of both 1
(entry 5) and 10 equiv (entry 6) of acetic acid (aq pKa )
4.7). In addition, acetic acid prevents formation of all but
approximately 10% of the rearranged phenol. However, if
the amount of acetic acid is increased to 100 equiv (entry
7), the competing reaction between acetic acid and NaBH4
becomes significant, and there is insufficient reducing agent
present to reduce more than 52% of the benzaldehyde.
Entries 8 and 9 demonstrate that the conversion increases
to 99% if the amount of NaBH4 is increased to 2 equiv
relative to the benzaldehyde and that the maximum amount
of the benzyl alcohol (94%) is again obtained when the
stoichiometry of NaBH4 and acetic acid is 1:10 (entry 9).
Entry 10 confirms that the benzyl alcohol should not remain
in solution longer than necessary to complete the reduction
or it will slowly rearrange to the corresponding phenol. Entry
11 demonstrates that there is essentially no improvement in
the conversion by using 3 equiv of NaBH4 and 30 equiv of
acetic acid, although there is a slight increase in the amount
of benzyl alcohol relative to that of the rearranged phenol.
One remaining question is whether this selective formation
of the benzyl alcohol is due to quenching of the intermediate
benzyl alkoxide by acetic acid or if it is due to reduction by
a more selective reducing agent that is generated in situ by
reaction of NaBH4 with acetic acid. For example, aldehydes
are chemoselectively reduced in the presence of ketones
using 2 equiv of in-situ-generated NaBH(OAc)310 or tetrabu-
tylammonium triacetoxyborohydride11 in benzene at 80 °C.
Alternatively, the cental aromatic ring can be functional-
ized with a polymerizable group through a one-carbon spacer
by brominating 2,5-bis[(4′-(n-alkoxy)benzoyl)oxy]toluenes
at the benzylic position, followed by esterification of the
resulting benzyl bromides with a carboxylate salt containing
the polymerizable group.4,5 However, substituents on the
mesogen such as siloxanes,6 oligo(oxyethylene)s,7 and thio-
ether8 groups are not stable to bromination. In contrast, the
benzyl alcohol route is cleaner and more widely applicable.
This paper therefore investigates the possibility of quenching
the intermediate benzyl alkoxide with either a proton to
generate the less reactive benzyl alcohol or a polymerizable
acid chloride to generate stable monomers. Since the neutral
benzyl alcohol will also slowly rearrange in solution, the
time required for the reduction step must be minimized using
a homogeneous reaction, rather than a slower heterogeneous
reduction.
With the exception of entries 1 and 12, Table 1 presents
the product distribution produced by reduction of 2,5-bis-
[(4′-(methoxy)benzoyl)oxy]benzaldehyde using NaBH4 in the
presence of a weak protonic acid, a strong protonic acid,
and an acid chloride. The reductions were carried out in THF,
with a minimum amount of DMSO required to solubilize
the benzaldehyde at room temperature. In the absence of an
additive (entry 1), reduction using 1 equiv of NaBH4 is
essentially quantitative (99% conversion) in 30 min, but
(10) Gribble, G. W.; Ferguson, D. C. J. Chem. Soc., Chem. Commun.
1975, 535-536.
(11) Nutaitis, C. F.; Gribble, G. W. Tetrahedron Lett. 1983, 24, 4287-
4290.
(12) Optimized Reduction of 2,5-Bis[(4′-(methoxy)benzoyl)oxyben-
zaldehyde (Entry 11, Table 1). A mixture of 2,5-bis[(4′-(methoxy)benzoyl)-
oxy]benzaldehyde4 (0.50 g, 1.2 mmol) in THF (20 mL) and DMSO (2.0
mL) was heated to dissolve the solids. After cooling, glacial acetic acid
(2120 µL, 37 mmol) was added, and the entire solution was immediately
added to a slurry of NaBH4 (0.14 g, 3.7 mmol) in DMSO (1.0 mL). After
the solution was stirred at room temperature for 30 min, the reaction mixture
was poured into ice-cooled 10% aqueous NaCl (50 mL), and CH2Cl2 (25
mL) was added to dissolve the precipitate. The aqueous layer was neutralized
with NaHCO3, and the two layers were separated. The aqueous layer was
extracted twice with CH2Cl2 (25 mL each). The organic extracts were
combined, washed once with 10% aqueous NaCl (30 mL), and dried over
Na2SO4. After filtration, the solvent was removed in vacuo to yield 0.50 g
(100%) of a white solid containing 96% 2,5-bis[(4′-(methoxy)benzoyl)-
oxy]benzyl alcohol, 3% 2-[(4′-methoxybenzoyloxy)methylene]-5-[(4′′-meth-
oxybenzoyl)oxy]phenol, and 1% 2,5-bis[(4′-(methoxybenzoyl)oxy]benzal-
dehyde. These values were calculated by comparison of the integrals of
the 1H NMR resonances at 4.65 ppm (s, ArCH2OH), 5.34 ppm (s,
ArCH2O2C-), and 10.21 ppm (s, ArCHO). The rearranged phenol is easily
(9) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734-736.
1330
Org. Lett., Vol. 2, No. 9, 2000
Pugh, Coleen
