Atom-economical synthesis of 3,3,3-trifluoropropanal dialkyl acetals through Pd/C catalyzed acetalization of 3,3,3-trifluoropropene

Article abstract of DOI:10.1039/c6ra03208g

A facile and efficient procedure for one-step synthesis of 3,3,3-trifluoropropanal dialkyl acetals from readily available 3,3,3-trifluoropropene (TFP) has been developed. The catalyst can be recycled for 4 times without obvious deactivation. This process provides a novel and atom-economical synthetic strategy for the preparation of functional CF₃-containing compounds.

Full text of DOI:10.1039/c6ra03208g

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Atom-economical synthesis of 3,3,3-
trifluoropropanal dialkyl acetals through Pd/C
catalyzed acetalization of 3,3,3-trifluoropropene†
Cite this: RSC Adv., 2016, 6, 39387
Received 3rd February 2016
Accepted 11th April 2016
Jian-Ping Kang, Ju-You Lu, Yang Li, Zhi-Xuan Wang, Wei Mao and Jian Lu*ab
ab
ab
ab
ab
ab
DOI: 10.1039/c6ra03208g
www.rsc.org/advances
13
A facile and efficient procedure for one-step synthesis of 3,3,3-tri- Li et al.
reported the synthesis of alkyl-3,3-dialkoxy-
fluoropropanal dialkyl acetals from readily available 3,3,3-tri- propionates by the acetalization of acrylates using a nano-
fluoropropene (TFP) has been developed. The catalyst can be recycled sized CS–Fe O –Pd catalyst. The facile formation of 3,3,3-tri-
3
4
for 4 times without obvious deactivation. This process provides a novel uoropropanal dialkyl acetals via the acetalization of alkene is
and atom-economical synthetic strategy for the preparation of func- expected. Triuoropropene (TFP), as an important fundamental
3
tional CF -containing compounds.
building block, is commercially available and its functionali-
14
15
zations e.g., addition reaction,
polymerization,
hydro-
16
17
formylation and hydroboration have been studied. However,
the acetalization of TFP has not been reported so far, presum-
ably due to the fact that TFP is gas at room temperature.
Here we rstly report a convenient and efficient method for
one-step preparing 3,3,3-triuoropropanal dialkyl acetals by the
acetalization of TFP with various alcohols using heterogeneous
Pd/C–CuCl system (Scheme 1).
2
Initially, we tried to seek an effective system for the Pd/C
catalyzed acetalization of TFP to produce 3,3,3-tri-
Triuoromethylated compounds have shown important appli-
1
2
cations in pharmaceutical chemistry, agrochemistry, and
3
materials science due to their unique chemical and biological
4
properties. Great efforts have been made to develop useful
methods for introducing the CF
3
group into organic
5
compounds. The building block approach is considered to be
6
a practical and powerful tool. Therefore, the development of
diverse CF
Meanwhile, the 3,3,3-triuoropropanal dialkyl acetals are
important CF -containing building blocks for 3,3,3-tri-
3
-containing building blocks is highly desirable.

uoropropanal dimethyl acetals (3a) with O as the oxidant. The
2
3
effects of different solvents on yield of reaction were investi-
gated including DMF, PEG400, toluene, THF, MeCN and MeOH
7

uoropropanoic acid, alkyl-3,3,3-triuoropropionate, and
8
3
b-CF alcohols.
(Table 1, entries 1–6). The results revealed that the solvent was
Several research groups had reported the synthesis of 3,3,3-
critical for the success of this reaction because the gas material
TFP should be dissolved in the solvent rstly before reaction.
7
–9
triuoropropanal dialkyl acetals.
However, their two-step
7
methods using expensive 1-chloro-3,3,3-triuoropropene or
-bromo-3,3,3-triuoropropene as a starting material have
9
2
restricted the synthetic application. more convenient
A
synthetic method involving fewer steps and the readily available
starting materials is highly desired.
Acetalization reaction of alkene is a powerful method for the
10
11
synthesis of acetals in a short sequence. Hosokawa and Jiang
II
reported the acetalization of acrylates by the use of Pd species.
12
Ishii et al. reported the acetalization of acrylates catalyzed by
2
Pd(OAc) /NPMoV supported on active carbon. Recently,
a
State Key Laboratory of Fluorine & Nitrogen Chemical, Xi'an 710065, China. Tel: +86
2
9 88291213. E-mail: lujian204@gmail.com
b
Xi'an Modern Chemistry Research Institute, Xi'an, 710065, China
†
Electronic supplementary information (ESI) available: Experimental procedures,
Scheme 1 Methods for synthesis of 3,3,3-trifluoropropanal dialkyl
acetals.
1
13
19
characterization data, H,
0.1039/c6ra03208g
C,
F
NMR, IR and MS spectra. See DOI:
1
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a
Table 1 Optimization of the reaction conditions
ꢀ
b
Entry
Solvent
Co-catalyst
Additive
T ( C)
Yield (%)
1
2
3
4
5
6
7
8
9
DMF
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuBr
CuSO
—
2
2
2
2
2
2
—
—
—
—
—
—
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
100
80
Trace
60
68
53
40
92
10
0
PEG400
Toluene
THF
MeCN
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
2
Fig. 1 Recyclability study of Pd/C catalyst. Reaction conditions: 1a (30
4
—
LiCl
0
mmol), catalyst (1 mol%), co-catalyst (2 mol%), solvent (20 mL), O
MPa, 120 C, 8 h. Yields determined by GC.
2
1
ꢀ
10
11
12
13
14
15
16
17
18
19
20
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
2
68
80
91
27
48
91
Trace
0
2
CH
Na
CO
3
SO
HPO
3
H
2
2
2
2
2
2
2
2
2
2
4
K
2
3
c
heterogeneous catalyst Pd/C with homogeneous catalyst PdCl2.
To our pleasure, the heterogeneous catalyst Pd/C displayed
similar activity to the homogeneous catalyst PdCl2 (Table 1,
entry 20). The benet using heterogeneous catalytic system is
that the catalyst is easily separated by ltration. The catalyst
recycle was also checked and it was reusable for at least 4 times
MeOH
—
—
—
—
—
—
—
d
MeOHe
MeOH
f
MeOH
MeOH
67
46
93
MeOHg
MeOH
120
2
with the addition of a small amount of CuCl (Fig. 1).
a
Reaction conditions: 1a (30 mmol), 2a (60 mmol), catalyst (1 mol%),
1 MPa,
1.4 MPa.
We next explored the scope and the utility of this method
with other olens and various alcohols. Table 2 shows the
acetalization of TFP with various alcohols. In almost all the
cases tested primary alcohols, the acetalization went smoothly,
giving a high yield of the desired products. The substituted
groups on the beta position of primary alcohol seemed to have
little inuence on the product yields (Table 2, entries 3i and 3k).
Isopropanol 2l, as secondary alcohol, could also be converted
into the corresponding acetal with moderate yield (Table 2,
entry 12). However, when cyclohexanol and tert-butyl alcohol
were explored, only a little desired product could be detected. In
general, the desired products could be obtained with higher
yields from primary alcohols than that from secondary alcohols.
Additionally, the alcohol containing aromatic ring such as
benzyl alcohol leads to the corresponding product of 23% yield,
which was also lower than that of primary alcohols because
a part of benzyl alcohol was transferred to benzaldehyde and
benzyl ether (Table 2, entry 13). Furthermore, the reaction of
ethylene glycol with TFP gave the desired product of 32% yield
co-catalyst (2 mol%), additive (1 mol%), solvent (20 mL), O
2
ꢀ
b
c
d
1
20 C, 8 h. Yields determined by GC.
O
2
0.6 MPa.
O
2
e
f
g
2 2
O 0 MPa. Catalyst free. PdCl (1 mol%).
Methanol was found to be the optimal solvent providing an
excellent yield of 3a. In addition, the effects of co-catalysts such
as CuCl , CuBr , and CuSO on yield of reaction were studied
2
2
4
(
Table 1, entries 6–8). Based on the results, CuCl
highest activity among the tested co-catalysts. No target product
was observed in the absence of CuCl (Table 1, entry 9). The co-
catalyst CuCl could play dual roles, which oxidized Pd to Pd
as co-oxidant and also acted as a ligand to prevent the deacti-
2
showed the
2
0
II
2
18
vation of the catalyst. The inuences of additives on catalytic
activity were also tested such as LiCl, CH SO H, Na HPO and
K CO (Table 1, entries 10–13). Although the addition of
CH
triuoropropenyl methyl ether (Michael adduct) also increased.
However, the use of dibasic Na HPO as an additive could
prevent the formation of the Michael adduct, leading to a little
decrease of TFP conversion. This result is consistent with
Hosokawa's studies. Finally, the effects of O pressure and
temperature were studied. A lower yield of 3a was obtained
3
3
2
4
2
3
3
3
SO H increased the conversion of TFP, the yield of 3,3,3-
2
4
(Table 2, entry 14). Unfortunately, when glycerol was used, the
reaction failed to afford the desired product. The reaction of 2-
aminoethanol also failed to afford the desired product but gave
10a
2
3o in 73% yield. Those alcohols containing ester, ketone such as
methyl glycolate, hydroxyacetone were found to afford a little
desired product.
when the reaction was run at the O pressure of 0.6 MPa (Table
2
1
, entry 14). However, increasing the reaction pressure to 1.4
MPa had no signicant effect on the yield of product 3a (Table 1,
entry 15). The reaction without O or Pd/C did not give the
In order to further demonstrate the utility of this protocol,
various alkenes were examined. Table 3 shows the acetalization
of various olens with methanol by the Pd/C–CuCl2 system.
Methyl acrylate, ethyl acrylate and n-butyl acrylate in methanol
provided the corresponding acetals in good yields (Table 3,
2
desired product at all (Table 1, entries 16 and 17). A decrease in
the temperature led to a decrease in the yield (Table 1, entries 18
and 19). Furthermore, we compared the catalytic activity of
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a
Table 2 The acetalization of TFP with various alcohols
Table 2 (Contd.)
b
b
Entry Alcohols
1
Products
Yield (%) Entry Alcohols
Products
Yield (%)
92(72)
1
4
5
56(32)
85(73)
2
3
89(74)
87(75)
1
a
Reaction conditions: 1a (30 mmol), 2 (20 mL), Pd/C catalyst (1 mol%),
CuCl (2 mol%), O 1 MPa, 120 C, 8 h. Yields determined by GC.
ꢀ
b
2 2
Number in parentheses is isolated yield.
4
5
6
7
8
89(82)
90(83)
83(80)
81(78)
80(78)
a
Table 3 The acetalization of various olefins with methanol
b
Entry
1
Alkenes
Products
Yield (%)
91
2
3
4
92
91
30
9
80(75)
78(73)
c
5
10
1
0
6
0
1
1
1
1
2
3
77(74)
70(62)
48(23)
a
Reaction conditions: 1 (30 mmol), 2a (20 mL), Pd/C catalyst (1 mol%),
ꢀ
b
c
ꢀ
CuCl
determined by GC.
2 2
(2 mol%), O 1 MPa, 50 C, 8 h. Isolated yield. 120 C yields
entries 1–3) which were the useful precursors for the prepara-
tion of various heterocyclic compounds. Acrylonitrile afforded
19
the corresponding product in 30% yield (Table 3, entry 4). The
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decrease in the p-electron density of olens due to competitive and CH
3
. So the results that there is no corresponding product
II
coordination ability of the CN group to Pd retards the reac- for them can be explained.
10a
tion. When styrene was explored, only 10% yield of 4f was
obtained because most of styrene were transferred to hypnone
and benzaldehyde (Table 3, entry 5). Unfortunately, when the
terminal alkenes bearing substituent on the alpha or beta
position such as 2-bromo-3,3,3-triuoropropene, 2-chloro-3,3,3-
triuoropropene, methyl methacrylate and methyl cinnamate
were explored, the reaction failed to afford the desired products.
To explore the possible reaction pathway, the Michael
adduct 3,3,3-triuoropropenyl methyl ether C was synthesised
Conclusions
In summary, we developed a new strategy for one-step synthesis
of 3,3,3-triuoropropanal dialkyl acetals via a simple Pd/C–
CuCl system catalyzed acetalization reaction of commercial
2
TFP with alcohols. The catalyst system can be recycled for 4
times without obvious deactivation. The wide scope to a large
number of primary alcohols and alkenes with electron-
withdrawing substituent, makes this strategy remarkably prac-
tical for the synthesis of functional acetal compounds. Atom-
economical characteristics and the recyclable catalyst system
of this method are benecial to industrial applications.
9
according to reference. Then the Michael adduct C was used to
react with methanol under the same conditions of model
reaction (Scheme 2). The desired product D was obtained in
9
7% yield.
10a,11b
Based on the previous mechanism reported
and our
results, a plausible pathway is provided in Scheme 3. In this
pathway, the key step is the production of the Michael adduct C, Acknowledgements
which has been detected by GC-MS in our experiments. First of
0
II
The authors wish to thank the National Natural Science Foun-
dation of China (Grant No. 21403163, 21503610) and Natural
Science Basic Research Plan in Shaanxi Province of China
(Program No. 2014JQ2062) for nancial support.
all, Pd was oxidized to Pd in the presence of CuCl and O as
2
2
1
1b,18a
the conventional redox couples.
(
Our experimental results
II
Table 1, entries 9, 16 and 20) also concludes that the Pd is the
II
true catalytic active species. Second, a Pd catalyst undergoes
oxypalladation with A to afford a organopalladium intermediate
B, followed by b-H elimination reaction to intermediate C.
Finally, the intermediate C undergoes oxypalladation again and
then affords the desired product D. For 2-bromo-3,3,3-
triuoropropene, 2-chloro-3,3,3-triuoropropene and methyl
methacrylate, their organopalladium intermediates B can not
occur b-H elimination reaction because b-H is replaced by Cl, Br
Notes and references
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