2
Tetrahedron
existing methods for the synthesis of dialkoxymethanes suffer
Table 1
from one or more of the following disadvantages: long reaction
time, high temperature, use of harmful raw material, use of
sensitive and costly reagent, etc.
Studies of the reaction conditons.
a
Entry Catalyst ( mol% ) Base (equiv )
Time ( h )
Yield (%)
trace
trace
32
b
1
2
3
4
5
6
7
8
IMesCuCl (2)
SIMesCuCl (2)
ICyCuCl (2)
IPrCuCl (2)
SIPrCuCl (2)
ICyCuCl (2)
--
KOH (2.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
BuOK (2.0)
BuOK (2.0)
BuOK (1.1)
12
12
12
12
12
2
b
b
b
b
c
c
c
trace
trace
95
52
76
t
t
t
24
12
ICyCuCl (2)
a
b
c
Isolated yield. The reaction was carried out under oxygen atmosphere.
Scheme 2 Synthesis of dialkoxymethanes
The reaction was carried out under argon atmosphere.
Transition metal catalysis is one of the most powerful tools
available to chemists for the development of cleaner and more
The scope of the substrates was investigated and the results
were listed in Table 2. We found that under optimized reaction
condition the transformation could be accomplished with various
alcohol substrates. The benzyl alcohols all could react efficiently
and universally to afford the corresponding dialkoxymethanes in
excellent yield, no matter whether the substituents were electron-
rich or electron-deficient (Table 2, entries 1 - 4). The position of
the substituent showed no obvious steric hindrance effect on the
dialkoxymethanes yields (Table 2, entries 1, 7, 8 and 4 - 6).
Similar to benzyl alcohols, heterobenzylic counterparts reacted
efficiently to afford the heterobenzylic formaldehyde
dialkylacetals in good yields (Table 2, entries 9 - 11). This
method was also suitable for aliphatic alcohols, we could get the
bis(hexyloxy)methane 2l in 77% yield (Table 2, entry 12). High
yield of tetrahydrofurfuryl formaldehyde dialkylacetal was
obtained from tetrahydrofurfuryl alcohol (Table 2, entry 13). For
the phenol and catechol, we could also get the desired products in
13
sustainable processes.
Recently N-heterocyclic carbenes
(
NHCs) have gained a prominent place in the chemist’s toolbox
14
due to their outstanding affinities to metal centers , which have
naturally led to their application in lot of organic
a
15
transformations . The strong electronic donating properties of
NHCs in conjunction with copper, yields catalyst which are often
very robust, demonstrating air, moisture and thermal stability. In
the decade, the Cu-NHC catalysts have been shown to
functionalize a large variety of substrates, including carbonyls,
alkenes, alkynes or aromatics. Here, we report an effective,
1
6, 17
simple and mild reaction using Cu-NHC complexs
as catalyst
for preparing symmetrical dialkoxymethanes derived from
primary alcohols in excellent yields. To the best of our
knowledge, there is no example has been reported in the
literature using of the Cu-NHC complexes to catalyze this
reaction.
o
moderate yield at 80 C (Table 2, entries 14-15).
Initially, we explored the reaction of 4-chlorobenzyl alcohol
Table 2
1
a with dichloromethane using potassium hydroxide as base
The preparation of dialkoxymethanes from dichloromethane
with alcohols using ICyCuCl as catalyst.
under the catalyst of kinds of Cu-NHC complexes (Figure 1) for
the preparation of dialkoxymethane 2a. We mainly got 4-
chlorobenzaldehyde when using the Cu-NHC as the catalyst
under oxygen atmosphere (Table 1, entries 1 - 5), but the desired
ether 2a could be isolated in 32% yield when using the ICyCuCl
as the catalyst (Table 1, entry 3). When the reaction was carried
out under argon atmosphere and the base was changed into
a
Entry
1
Product
Yield (%)
t
BuOK, the reaction was finished within 2 hours at ambient
9
5
temperature and the desired product was isolated in 95% yield
2a
2
(
Table 1, entry 6). Without the ICyCuCl as catalyst, the desired
ether 2a was only isolated in 52% yield for 24 h (Table 1, entry
). Decreasing the amount of base to 1.1 equivalents coursed the
8
5
2
b
7
3
4
9
9
8
4
reducing the yield of product dramatically (Table 1, entry 8).
2
c
2
d
5
9
2
2
e
f
6
7
9
9
1
8
2
2
g
Figure 1 The structure of the Cu-NHCs
Zhan, Lewu
