A.M. Rabon, J.G. Doremus and M.C. Young
Tetrahedron 85 (2021) 132036
promoting acetalization as well.
the reaction was actually at the expected temperature and not a bit
higher, we ensured the temperature had stabilized using a ther-
mometer in an oil bath prior to setting-up the reactions. We next
performed the reaction, but ensured sufficient air circulation to
keep the system at room temperature (Entry 3), which still gave
30% yield of the product (also monitored using a thermometer and
oil bath). To compare these results to the background reaction, we
next looked at the effect of running the reaction at room temper-
ature, but keeping the flask in the dark (Entry 4), in which case a
lower 15% yield was observed. By leaving the reactions on a
windowsill exposed to ambient sunlight (but at room temperature,
Entry 5) we found comparable yields to running the reactions
under the lamps at room temperature.
When the MOF was excluded, only 7% yield of acetal was found
under the photothermal conditions (Entry 6). To ensure the MOF
was directly involved as opposed to possible degradation products,
we next screened ZrCl4 (Entry 7) and the ligand trimesic acid
(Entry 8). Notably, in the case of ZrCl4 we expect the identity of the
active catalyst to more accurately reflect the degradation products
of the MOF after solvolysis, rather than actually being ZrCl4 [38]. In
both cases no desired product was observed, suggesting that the
activity is specific to the MOF, and that the individual components
even slow the background reaction. We next studied how the
catalyst loading impacted the conversion. We had assumed that
increasing the amount of framework would increase the conversion
e however, the reaction appears to be hindered by additional
catalyst (Entries 9e12). We noticed from direct analysis of the
crude reaction by GC-MS that when the conversion was high but
yield was low, sometimes significant amounts of additional side
products were observed, including benzyl alcohol and methyl
benzoate. Notably, the catalyst loading was based on the molecular
weight for [Zr6O4(m3-OH)4(FA)6(BTC)2], which will be slightly
undervalued since it ignores the undefined amount of residual
solvent that will be filling the pores.
2. Results and discussion
MOF-808 was synthesized according to a known solvothermal
procedure [35], and was confirmed by comparison of the powder x-
ray diffraction and FTIR data with literature data. While many
acetalization catalysts operate under thermal conditions, we were
interested in recent work using thiourea catalysts for acetalization
that are activated by light at room temperature [36]. The pKa of the
photo excited state was found to be lower, thereby increasing the
rate of acid catalysis. Considering the potential of MOF-808 to
absorb light (lmax ¼ ~254, 292 nm when suspended in MeOH), we
considered that photoactivation with light could provide similar
access to increased acidity for acid-based catalysis. We therefore
began investigating the activity of MOF-808 for the acetylation of
aldehydes under mild photolytic conditions (Table 1) using 2-
naphthaldehyde (1a) as a model substrate in methanol to prepare
the dimethyl acetal 2a. While GC-MS is a common analytical
technique used to analyze product yield, we found that analyzing
samples directly in the alcohol solvent gave some conversion to
acetal product, and so the yield and conversion was instead
determined by 1H NMR using an internal standard after a simple
work-up procedure.
Gratifyingly, we were able to find that by simply placing our
samples on a stir plate between two 26W fluorescent work lamps
overnight, the reaction could be achieved with 90% conversion and
72% yield as determined by NMR (Table 1, Entry 1). Under the re-
action conditions, the temperature was found to stabilize at 45 ꢀC,
which suggested that perhaps the reaction was thermal in nature.
However, in the absence of light the conversion and yield were both
lower (Entry 2), suggesting an important role for light. To ensure
We next explored the reaction on different substrates (Fig. 1). 2-
Naphthaladehyde worked well to give 2a, while 1-naphthaldehyde
gave a lower yield of 2b. Benzaldehyde worked relatively well
based on TLC and GC-MS analysis of the crude reaction (2c), how-
ever, the volatility of the product caused the average yields to be
lower. Larger 9-anthracene carboxaldehyde as well as 1-pyrene
carboxaldehyde could be converted to 2d and 2e respectively,
although the conversion and therefore yield were lower. The
sterically-hindered o-tolualdehyde was not very effectively con-
verted into 2f during the reaction, but the less sterically-hindered
m- and p-tolualdehydes gave the acetal products 2g and 2h in
much better yields. We reasoned that salicylaldehyde might be a
better substrate despite sterics thanks to intramolecular hydrogen
bonding, but the acetal 2i was recovered in relatively low yield.
Surprisingly, p-anisaldehyde also gave low yield of acetal 2j. Ter-
ephthaldehyde was a very effective substrate, giving full conversion
and more importantly good selectivity for the diacetal 2k. Aliphatic
aldehydes were not very efficiently converted (2l and 2m), while
heterocyclic acetal 2n was not observed under the current condi-
tions (only the 2-furfural starting material was recovered). Notably,
when we investigated the crude reaction mixtures by NMR and GC-
MS, we found the majority of the mass balance for these reactions
were aldehyde and acetal, with trace amounts (<5%) of the corre-
sponding esters and cinnamaldehydes. We also evaluated the re-
action conditions for the acetalization of D-(þ)-glucose, but not
Table 1
Optimization of the photothermal acetalization of 2-naphthaldehyde with Meth-
anol.
Entry
Reaction Conditions
Conversion (%)
Yield (%)
1
2
3
4
5
6
7
8
Absence of Light
Absence of Heat
Absence of Light RT
Natural Light RT
90
85
54
49
55
7
17
13
77
80
82
80
72
58
30
15
36
7
0
0
29
28
10
15
Absence of MOF-808
ZrCl4 as Cat.
Trimesic Acid as Cat.
20 mol% MOF-808
30 mol% MOF-808
40 mol% MOF-808
50 mol% MOF-808
9
10
11
12
only was the a-methylglucoside not observed, partial dehydration
a
“Standard Conditions”: A 7.5 mL vial was charged with 2-naphthaldehyde
(0.1 mmol, 15.6 mg), MOF-808 (0.01 mmol, 10 mol%, 13.5 mg), and MeOH (1 mL).
The vial was sealed with a PTFE-lined cap and stirred under two 26-W twin-tube
fluorescent work lights at 45 ꢀC [37]. After cooling to room temperature, the
MeOH was evaporated and replaced with CDCl3 and a drop of dibromomethane
(DBM) standard added.
of the glucose was observed to occur.
Because the system could promote formation of acetals in
methanol, we next considered whether or not the reverse hydro-
lysis could be achieved by using water. MOF-808 is known to be
relatively robust in water at elevated temperatures, so the reaction
2