A novel vapor-phase catalytic synthetic approach for industrial production of 1,1,1,3,3,3-hexafluoroisopropyl methylether

Article abstract of DOI:10.1016/j.apcata.2020.117416

1,1,1,3,3,3-Hexafluoroisopropylmethyl ether (HFE-356mmz) is an important substitute for chlorofluorocarbons and hydrochlorofluorocarbons due to its zero ozone depletion potential and low global warming potential. However, mass production of HFE-356mmz remains a long-standing challenge. Herein, we applied metal fluorides as catalysts in the methylation of 1,1,1,3,3,3-hexafluoroisopropanol to produce HFE-356mmz for the first time. The catalyst not only improves the synthetic efficiency, but also makes the reaction solvent-free. The pollution-free, recyclable, and continuous synthetic process enables industrial production of HFE-356mmz. To optimize the synthetic efficiency, a series of metal fluorides (AlF₃, MgF₂, CaF₂, SrF₂, and BaF₂) was used, among which MgF₂ exhibited the highest activity. Through careful examination of each metal fluoride, it was found that the activity of the catalyst was determined by co-operative action of the surface acid–base properties and the total amount of surface acid sites. Based on these results, a rational mechanism for the vapor-phase methylation was proposed.

Full text of DOI:10.1016/j.apcata.2020.117416

Journal Pre-proof
A novel vapor-phase catalytic synthetic approach for industrial production
of 1,1,1,3,3,3-hexafluoroisopropyl methylether
Wei Li, Gang Yang, Fengniu Lu, Xiaoling Zhang
PII:
S0926-860X(20)30009-0
DOI:
https://doi.org/10.1016/j.apcata.2020.117416
APCATA 117416
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To appear in:
Applied Catalysis A, General
Received Date:
Revised Date:
Accepted Date:
16 October 2019
10 January 2020
13 January 2020
Please cite this article as: Li W, Yang G, Lu F, Zhang X, A novel vapor-phase catalytic
synthetic approach for industrial production of 1,1,1,3,3,3-hexafluoroisopropyl methylether,
Applied Catalysis A, General (2020), doi: https://doi.org/10.1016/j.apcata.2020.117416
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A novel vapor-phase catalytic synthetic approach for
industrial production of 1,1,1,3,3,3-hexafluoroisopropyl
methylether
Wei Li, Gang Yang, Fengniu Lu, Xiaoling Zhang*
Department of Chemistry, School of Science, Beijing Institute of Technology, 5 South
Zhongguancun Street, Beijing, 100081, China
*
Corresponding Author:
Email: zhangxl@bit.edu.cn
Tel: +86-10-88875298
Graphical Abstract
Highlights


A novel synthetic method based on vapor-phase catalytic methylation was presented
Environmental friendly 1,1,1,3,3,3-hexafluoroisopropylmethyl ether was synthesized
1




The synthetic process is continuous and pollution-free
The reaction is catalyzed by alkaline earth metal fluorides, with MgF
A mechanism for the catalytic methylation was proposed
2
most active
ABSTRACT. 1,1,1,3,3,3-Hexafluoroisopropylmethyl ether (HFE-356mmz) is an important
substitute for chlorofluorocarbons and hydrochlorofluorocarbons due to its zero ozone depletion
potential and low global warming potential. However, mass production of HFE-356mmz
remains a long-standing challenge. Herein, we applied metal fluorides as catalysts in the
methylation of 1,1,1,3,3,3-hexafluoroisopropanol to produce HFE-356mmz for the first time.
The catalyst not only improves the synthetic efficiency, but also makes the reaction solvent-free.
The pollution-free, recyclable, and continuous synthetic process enables industrial production of
HFE-356mmz. To optimize the synthetic efficiency, a series of metal fluorides (AlF
CaF , SrF , and BaF ) was used, among which MgF exhibited the highest activity. Through
careful examination of each metal fluoride, it was found that the activity of the catalyst was
3
, MgF ,
2
2
2
2
2
determined by co-operative action of the surface acid–base properties and the total amount of
surface acid sites. Based on these results, a rational mechanism for the vapor-phase methylation
was proposed.
KEYWORDS: 1,1,1,3,3,3-hexafluoroisopropylmethyl ether, vapor-phase catalytic methylation,
metal fluoride, Lewis acidity, Lewis basicity.
1
. Introduction
Owing to the implementation of the Montreal Protocol, the chlorofluorocarbons (CFCs) and
hydrochlorofluorocarbons (HCFCs), which show high ozone depletion potentials (ODP) and high
global warming potentials (GWP), were banned from using [1]. Thereafter, hydrofluoroethers
2

(HFEs) were considered as potential substitutes for CFCs and HCFCs due to their zero ODP and
relatively short atmospheric lifetimes [2-4]. Among the various HFEs, 1,1,1,3,3,3-
hexafluoroisopropylmethyl ether (HFE-356mmz) has attracted particular attention because it
exhibits an ODP of zero, an atmospheric lifetime of 62 days, a GWP100 value of 6, weak
flammability, high chemical stability, and low toxicity [3-6]. These advantageous properties
enable huge application potentials of HFE-356mmz in coolants, solvents, cleaners, and the like.
As a result, mass production of HFE-356mmz with excellent synthetic efficiency is highly
desired.
Up to now, a number of synthetic strategies for HFE-356mmz from different starting
materials have been reported (Scheme 1). One of the most popular methods is the liquid-phase O-
methylation of 1,1,1,3,3,3-hexafluoroisopropanol (HFiP) using (CH
carbonate (DMC) [8], or CH X (X = Cl, Br, I) [9] as the methylating reagent. However,
CH SO is highly toxic and the reaction using DMC needs to be carried out in an autoclave
3
)
2
SO
4
[7], dimethyl
3
(
3
)
2
4
under a harsh condition. In addition, strong bases are required as catalysts in all these reactions,
leading to cumbersome post-processing problems. All the other methods employ high-cost
starting materials such as 1,1,3,3,3-pentafluoro-2-meth-oxyprop-1-ene [10], methyl-
3
1
,3,3trifluoro-2-hydroxy-2-(trifluoromethyl) propanoate [10], 2-methoxymalo-nonitrile [11],
,1,1,3,3,3-hexafluoro-2-(trichlorometh-oxy) propane [12], and sevoflurane [13]. Moreover, most
of these methods are based on liquid-phase reactions which are of intermittent operation and high
pollution due to the production of a large amount of unrecyclable solvents and base.
Therefore, there is still no suitable method for mass production of HFE-356mmz so far.
To develop a green, pollution-free, and continuous process for the synthesis of
HFE356mmz, we came up with the idea of using a Lewis acid catalyst, namely, metal fluoride,
3

because Lewis acid catalysts (eg. FeCl
3
, AlCl
3
, and zeolites) [14, 15] and Lewis base catalysts
(
eg, K CO , CsF/α-Al , and MgO) [16, 17] were reported to be constructive in the methylation
2
3
2
O
3
reaction. The metal fluoride was selected because it can resist the corrosive HF, which might be
produced from the decomposition of HFiP at high temperatures. In addition, metal fluorides, in
many cases, are powerful catalysts to help achieve green gas-phase reactions such as
dehydrohalogenation reaction [18], Cl/F exchange reaction [19] and isomerisation reaction [20].
To our best knowledge, the metal fluoride has not been disclosed in any open literature as a
catalyst in the methylation reaction. Herein, we achieved a green vapor-phase synthetic approach
for HFE-356mmz for the first time by utilizing metal fluoride as the catalyst. As shown in
Scheme 2, the methylation of HFiP using DMC gave rise to HFE-356mmz and a series of
volatile by-products. To achieve high synthetic efficiency, a number of metal fluorides with an
order of decreasing Lewis acidity (AlF
3
, MgF
2
, CaF
2
, SrF
2
, and BaF ) were prepared and tested.
2
MgF with moderate Lewis acidity and moderate Lewis basicity exhibited the highest activity.
2
Through systematic investigation of all these metal fluorides, their catalytic activity was found to
depend on the combination of the surface acidity and basicity, as well as the total amount of
surface Lewis acid sites. In addition, the MgF
2
showed high stability over 1000 hours and HFE-
3
56mmz in 50 kg scale could be prepared, suggesting great potential of the synthetic route for
industrial production of HFE-356mmz. Accordingly, a rational mechanism of the vapor-phase
methylation was proposed at the end. Our study not only paves the way for industrial production
of HFE-356mmz, but also expands the application of metal fluorides.
4

Scheme 1. Reported synthetic routes for HFE-356mmz.
Scheme 2. Synthesis of HFE-356mmz through metal fruoride catalysed methylation of
HFiP using DMC.
2
．Experimental Section
2
.1. Preparation of the catalysts
Metal fluorides (AlF , MgF , CaF
corresponding metal oxides (Al , MgO, CaO, SrO, and BaO) [21, 22], in which MgO and
Al were obtained by a precipitation method. The typical process for synthesizing MgF was as
follows: Mg(NO (148 g, 1.0 mol) was dissolved in distilled water (400 mL) and stirred for 1 h,
then ammonium hydroxide (5%) was slowly added to the solution at room temperature until pH
8.5 was reached. The precipitate formed was filtered off and washed with distilled water to
3
2
2
, SrF
2
, and BaF ) were prepared by fluorination of the
2
2
O
3
2
O
3
2
)
3 2
=
5

remove nitrate ions. After drying at 120 °C for 4 h and calcining at 500 °C for 12 h in a muffle
furnace, the solid was ground and pelletized. The MgO pellets prepared above were packed on
1
1
monel alloy reactor and fluorinated by a mixture of N (100 ml min ) and HF (100 mL min ) at
2
1
2
00 °C for 2 h. Then pure HF (100 mL min ) passes through the reactor at 200 °C and 250 °C
1
for 2 h each. Finally, the remaining HF on the catalyst was blown away by N
2
(100 ml min ) for
. CaF , SrF , and
were prepared by fluorination of commercially available CaO (Aladdin, 99.9%), SrO
1
2 h. AlF
3
was prepared from Al(NO
3
)
3
in a procedure similar to that of MgF
2
2
2
BaF
2
(Aladdin, AR), and BaO (Aladdin, AR), respectively, in a procedure similar to the preparation of
MgF from MgO.
2
2
.2. Characterization of the catalysts
Unless otherwise mentioned, characterization of all the catalysts was done after being used
in the methylation reaction for over 4 h.
The structures of the catalysts were determined by X-ray diffraction (XRD) in the range of
2
θ = 10–90 , using a Bruker D8 Advance diffractometer and Ni-filtered Cu Kα radiation (λ =
1
.540 Å).
The surface areas of the catalysts were determined by N
Autosorb-iQ-C equipment. All the samples were degassed for 3 h at 250 °C prior to the N
physisorption. The surface areas were calculated according to the Brunauer–Emmett–Teller
BET) equation.
Acidity of the catalysts was determined by temperature programmed desorption of NH
2
physisorption in a Quanta-chrome
2
(
3
(
NH
3
-TPD) (Quantachrome Autosorb-iQ-C, USA). All the samples (100 mg) were treated in He
3
1
(
30 cm min ) at 250 °C for 1 h and then exposed to a 5% NH
3
/He stream for 60 min at 100 °C.
The weakly adsorbed NH was removed by flushing with He at 100 °C for 6 h. The temperature
3
6

1
was then increased to 500 °C at a rate of 10 °C min , and the liberated NH
on-line gas chromatograph with a thermal conductivity detector. Basicity of the catalysts was
determined by temperature programmed desorption of CO (CO -TPD) measurements which was
performed in a manner similar to the NH -TPD measurements, except that CO was injected
instead of NH
3
was detected by an
2
2
3
2
3
.
The nature of surface acid sites was determined by fourier-transform infrared spectroscopy
FTIR) using pyridine as a probe molecule and a Thermo scientific (Nicolet 380)
(
spectrophotometer. Sample wafer was formed by pressing 20–40 mg of a catalyst at 5 tons cm 2,
which was transferred to a sample holder made of quartz. All the samples were initially degassed
at 200 °C for 5 h and then a background spectrum was recorded after cooling the sample to room
temperature. The spectra were recorded at room temperature before the adsorption of pyridine
and after the evacuation of pyridine (absorbed at 40 °C) at 250 °C, respectively.
2
.3. Test of catalyst and analysis of product
The vapor-phase methylation of HFiP (Sinochem, Lantian, >99%) with DMC (Aladdin, >
9%) was carried out in a down flow reactor at 250 °C under 101.1 kPa. The catalysts (particles
with 0.8-1.2 mm diameter, 20 g) were treated in situ at 250 °C under N flow for 4 h before the
9
2
reaction. A mixture of HFiP and DMC with a 1:2 molar ratio was fed using a syringe pump.
Standard catalytic tests were conducted at a contact time of 11.4 s. The outlet reaction mixture
was analysed by gas chromatography (GC) using an GC-2014C (Shimadzu) equipped with a DB-
VRX capillary column (30 m 0.45 mm 0.25 μm), the temperature of which was set as
1
follows: 50 °C for 5 min, heating to 200 °C at a rate of 10 °C min , and then holding at 200 °C
for 8 min. The temperature of the injection port and the hydrogen flame ionization detector were
7

1
maintained at 200 °C and the He carrier gas was introduced at a rate of 10 mL min . Besides,
the stability of MgF was evaluated using the same reaction condition for 1000 h.
The conversion of HFiP (X ) was calculated as: X = ΣY /(ΣY +Y ), where ΣY
molar fraction of products formed from HFiP and Y is the outlet molar fraction of HFiP. In
order to calculate the X , the GC relative response factor of HFiP to HFE-356mmz was
2
H
H
i
i
P
i
is the
P
H
measured preliminarily. HFiP (1 mmol) and HFE-356mmz (1 mmol) were mixed and warmed
in a sample bag approximately 1 L in volume. The mixture was then carried to the GC by a
carrier gas (He) under warm atmosphere and their relative GC areas were measured. Finally, the
GC relative response factor was obtained and a ratio of f(HFiP):f(HFE-356mmz) = 1:1.49 was
used to calculate the X
The selectivity of product (S
product and ΣY is the amount of HFiP reacted.
H
.
i
) was determined as: S
i
= Y
i
/ΣY
i
, where Y is the amount of
i
i
3
. Results and Discussion
3
.1. Synthesis of HFE-356mmz
The HFE-356mmz was synthesized through methylation reaction of HFiP using DMC as
the methylation reagent over different metal fluorides (AlF , MgF , CaF , SrF , or BaF ) at 250
C under 101.1 kPa. According to the GC analysis results of the outlet reaction mixture,
3
2
2
2
2
°
methanol (CH
3
OH) and methyl ether (CH
3
OCH
3
) were produced in addition to the product HFE-
OH was probably formed by
might be generated through the condensation
3
56mmz and the unreacted raw materials (DMC and HFiP). CH
3
the methylation reaction of DMC while CH
reaction of CH
making the reaction solvent-free. Since no by-product from HFiP was detected in the outlet
3
OCH
3
3
OH [23]. Therefore, all the by-products are volatile under the reaction condition,
8

reaction mixture, the selectivity of HFE-356mmz was considered to be 100%. Such a highly
efficient vapor-phase synthetic approach is applicable for industrial production of HFE-356mmz
because the synthetic process is pollution-free and continuous and all the starting materials are
recyclable.
Table 1. Conversion of HFiP (X
) over various catalystsa
H
b
Total activity (mmol h 1 m 2)
c
Catalyst
AlF
MgF
CaF
X
H
(%)
3
2.6
4.3
0.04
2.01
9
2
2
84.9
3.3
1.61
1.34
5
SrF
2
BaF
2
3.7
0.25
aReaction condition: temperature = 250 °C; pressure = 101.1 kPa; contact time = 11.4 s; injection rate of HFiP =
1
b
1
H
39.8 mmol h ; running time = 4 h. X was determined by GC versus a calibrated internal standard.
cTotal activity (mmol h 1 m ) was determined by the molar reaction rate of HFiP and the specific surface area of the
2
catalysts.
Notably, even under the same reaction condition, the conversion of HFiP (X
using different metal fluorides, which follows an order of MgF (94.3%) > CaF (84.9%) > SrF
53.3%) > BaF (3.7%) > AlF (2.6%) (Table 1). Such a difference should be originated from the
H
) is different
2
2
2
(
2
3
different catalytic activity of each catalyst. To explore the reasons of the different catalytic
activity, all the catalysts were carefully characterized after being used in the methylation reaction.
9

3
3
.2. Characterization of the catalysts
.2.1. Structure
Fig. 1 XRD profiles of the catalysts used after the methylation reaction: a) AlF
3
(PDF: 801007),
b) MgF (PDF: 72-2231), c) CaF (PDF: 75-0097), d) SrF (PDF: 86-2418), and e) BaF
2
2
2
2
(PDF: 85-1341).
The structure of all the catalysts were analysed by XRD and the results were summarized in
Fig. 1. As shown in Fig. 1a, the XRD profile of AlF
3
displays diffraction peaks at 2θ = 25 ,
4
2.4 ,
5
1
1.6 , and 57.8 , respectively, indicating a hexagonal crystalline structure (ICCD, PDF:80-
007).
All the other alkaline earth metal fluorides (MgF
2
, CaF
2
, SrF
2
, and BaF ) show broad reflexes
2
(Fig. 1a–d). The maxima of their diffractograms are in good agreement with those of the
1
0

corresponding crystal fluorides published previously [18]. Therefore, all of the metal fluorides
are of crystalline structures.
3
.2.2. Surface area
Table 2. Surface properties of the investigated catalysts
2
1
3
1
Catalyst
AlF
MgF
CaF
Surface Area (m g )
Pore Volume (cm g )
Average Pore Size (nm)
3
100.1
0.138
0.176
5.5
6
5.6
10.7
2
2
73.6
5.6
0.249
0.161
13.5
11.5
5
SrF
2
BaF
2
20.9
0.168
30.6
The surface properties of all the catalysts were summarized in Table 2, according to which
2
1
AlF
3
exhibits the largest surface area (100.1 m g ) whereas BaF
2
possesses the smallest one
, CaF , and SrF ) show
analogous surface areas, which falls in the range of 55.6–73.6 m g . In addition, the pore
volumes and the average pore sizes of MgF , CaF , and SrF , which are within the ranges of
2
1
(
20.9 m g ). All the other alkaline earth metal fluorides (MgF
2
2
2
2
1
2
2
2
3
1
0
.161–0.249 cm g and 10.7–13.5 nm, respectively, are not significantly different.
Based on the surface area of the catalysts (Table 2) and the X of HFiP in the methylation
H
reaction (Table 1), the total activity of the metal fluorides was calculated (Table 1). All the
catalysts were active for the reaction. In spite of the medium surface area of MgF , it exhibits the
possessing the largest surface
2
1
2
highest activity (2.01 mmol h m ). In sharp contrast, the AlF
3
1
1

1
2
area shows the lowest activity (0.04 mmol h m ). Therefore, the activity of these catalysts
should not be dominated by their surface properties 3.2.3. Acidity
Fig. 2 NH -TPD profiles of catalysts used in this study.
3
Since the acid sites on the surface of a catalyst are closely related with its catalytic activity,
the surface acidity of all the catalysts was analysed by NH -TPD. According to the acid strength
measurement by Narayanan [24], the desorption temperature of NH at the range of 80–150 °C,
50–300 °C, and 300–450 °C represent weak, medium, and strong acid strength, respectively. As
shown in Fig. 2, the NH -TPD profile of AlF displays two desorption bands (180°C and 320 °C)
and a shoulder ( 430 °C), which can be ascribed to the NH adsorbed on medium and strong acid
sites of the catalyst, respectively. In contrast, the NH -TPD profile of BaF displays a weak band
at 140 °C, reflecting the existence of weak acid sites only. For MgF showing the desorption
peaks at 100 °C and 275 °C and CaF with the desorption peaks at 130 °C and 240 °C, weak and
medium acid sites coexist. Desorption of NH from SrF gives rise to a weak band at about 160
C, indicating medium acid strength of the catalyst.
3
3
1
3
3
3
3
2
2
2
3
2
°
1
2

Fig. 3. FTIR spectra recorded after pyridine adsorption on different catalysts at 40 °C, followed
by evacuation of pyridine at 250 °C: a) AlF , b) MgF , c) CaF , d) SrF , and e) BaF . Table 3.
Acid-base properties of the catalysts used in this study
3
2
2
2
2
Amount of Acidc ( mol g 1)
Aciditya
Basicityb
Catalyst
Brønsted Acid
Lewis Acid
AlF
MgF
CaF
3
strong
weak
12.7
290.5
2
medium
medium
medium
medium
5.5
1.2
66.1
19.5
2
medium
weak
medium, strong
0.5
0.1
12.1
0.3
SrF
2
BaF
2
strong
aDetermined by NH
-TPD. Temperature range: 100–500 °C. Determined
b
3
c
by CO
2
-TPD. Temperature range: 100–500 °C. Calculated by
1
1
integrating the characteristic FTIR bands (1450 cm , 1490 cm , and
1
1
600 cm ) of all catalysts recorded after the adsorption of pyridine at 40
°
C and subsequent evacuation at 250 °C.
To further identify the nature of the surface acid sites, FTIR spectra of all the catalysts were
recorded after the adsorption of pyridine at 40 °C and subsequent evacuation of pyridine at 250
°
C. Only the bending and stretching frequency ranges were shown (Fig. 3). The absence of the
1
characteristic bands of Brønsted acid sites at 1640 and 1540 cm suggests negligible Brønsted
1
3

acid site in all of the catalysts [25]. On the contrary, the stretching vibrations of pyridine
coordinatively bonded to Lewis acid sites of AlF
3
, MgF
2
, CaF
2
, and SrF , which are located at
2
1
1
1
1
440–1450 cm , 1480–1500 cm , and 1600 cm , are observed. No Lewis acid site is detected
on the surface of BaF
of BaF
gradually from 1598 cm (SrF
2
due to its weak acid strength, which agrees well with the NH TPD profile
3
1
2
presented in Fig. 2. Notably, the wavenumber of the band ( 1600 cm ) increases
1
1
1
2
, Fig. 3d) to 1600 cm (CaF
2
, Fig. 3c) to 1608 cm (MgF
2
, Fig.
−
1
1
3
b) and to 1626 cm (AlF
3
, Fig. 3a). This is because the 1600 cm band is very sensitive to the
strength of acidity, which shifts to higher frequencies with stronger acidities [26, 27, 28].
Therefore, the acidity of the four catalysts SrF , CaF , MgF , and AlF increases in sequence. In
addition, the total amount of the absorbed pyridine, namely, the total Lewis acid amount of all the
2
2
2
3
−
1
−1
−1
catalysts, was estimated by integrating the bands around 1450 cm , 1490 cm , and 1600 cm ,
1
1
which decreases in the following order: AlF
3
(290.5 mmol g ) > MgF
2
(66.1 mmol g ) > CaF
2
1
1
1
(
19.5 mmol g ) > SrF
2
(12.1 mmol g ) > BaF
2
(0.3 mmol g ) (Table 3).
According to the study of the acidity mentioned above, the catalysts can be classified into
three categories based on the scale of their Lewis acidity: the catalyst with strong Lewis acid
centers (AlF ), the catalysts with medium strength of Lewis acid centers (MgF , CaF and SrF
and the catalyst with weak Lewis acid centers (BaF ) (Table 3). 3.2.4. Basicity
3
2
2
2
),
2
1
4

Fig. 4 CO -TPD profiles of catalysts used in this study.
2
The basicity of the catalysts was evaluated by CO
2
-TPD, the profiles of which were
indicative of the presence of basic sites with different strengths (Fig. 4). As reported previously,
◦
◦
◦
the bands at temperatures of 100 C, 200 C, and > 300 C are attributed to desorption of CO
interacted with sites having weak, medium, and strong basic strength, respectively [29, 30]. The
CO -TPD profile of BaF displays a broad band at about 410 °C, evidencing the presence of
strong basic sites. Whereas both medium and strong basic sites coexist on the surface of SrF
indicated by its two broad desorption bands at about 210 °C and 330 °C. For MgF and CaF
medium basic sites are predominant because desorption of CO completed at 250 °C. For AlF
desorption of CO gives rise to a weak desorption band at about 140 °C, suggesting the existence
of weak basic sites only. Based on these results, the catalysts can be divided into three types: the
catalysts with strong Lewis base centers (BaF and SrF ), the catalysts with medium strength of
Lewis base centers (MgF and CaF ), and the catalyst with weak Lewis base centers (AlF
Table 3).
2
2
2
2
, as
2
2
,
2
3
,
2
2
2
2
2
3
)
(
1
5

Based on the characterization of the acidity and basicity of the metal fluorides mentioned
above, the Lewis acidity decreases from AlF to MgF to CaF to SrF to BaF , while the Lewis
basicity increases. With this behaviour, the predominance of the acid–base pair in these catalysts
changes from acid site (AlF ) to basic site (SrF and BaF ), while MgF and CaF exhibit
medium acidity and basicity. Since MgF and CaF show the highest activity and largest X
3
2
2
2
2
3
2
2
2
2
2
2
H
in
the methylation reaction among all the catalysts, catalyst with medium surface acidity and
basicity should be more favourable for the methylation reaction of HFiP.
In addition, the lifetime of MgF
HFE356mmz remained unchanged in 1000 hours, and the conversion of HFiP decreased slowly
from 94.8% to 85.1%, suggesting good stability and high activity of MgF
2
was evaluated. As shown in Fig. 5, the selectivity of
2
.
Fig. 5 The conversion of HFiP (red dots) and selectivity of HFE-356mmz (black squares) over
000 hours. Reaction conditions: temperature = 250 °C; contact time = 11.4 s.
1
1
6

3
.3. Reaction mechanism
Scheme 3. Plausible mechanisms for methylation of HFiP with DMC over the catalysts.
The importance of acidity and basicity of the catalyst in promoting the vapor-phase
methylation reaction of HFiP can be further rationalized by the reaction mechanism using DMC
as the methylation reagent. Beutel [31] proposed a mechanism based on in situ spectroscopic
studies of the alkylation of phenol using DMC, where DMC was activated by the Lewis acid
sites of the zeolite NaX catalyst through complexation of its ester oxygen or carbonyl oxygen
+
atoms with the Na ions while phenol was activated by Lewis base site of the catalyst via
hydrogen bonding. Jyothi et al. [32] proposed a similar mechanism for the vapor-phase
methylation reaction of DMC making use of both the acid and the basic sites on the surface of
the catalysts. Inspired by these studies, we proposed a reasonable mechanism for the vapor-phase
methylation reaction of HFiP using DMC as the methylation reagent (scheme 3). The first step
was the adsorption of DMC and HFiP on the Lewis acid and basic sites of the surface of the
metal fluoride catalyst, respectively. Specifically, DMC was adsorbed through coordination of its
carbonyl oxygen to the unsaturated metal center of the catalyst and HFiP was adsorbed via
hydrogen bonding to the basic fluoride atoms of metal fluoride. Then, the nucleophilic oxygen
atom of HFiP attacked the carbon atom of the methyl group in DMC. Finally, the product
HFE356mmz, together with the by-products (CO
2
and CH OH), was produced and the catalyst
3
1
7

was regenerated. In addition, CH
condensation of CH OH.
3
OCH , detectable in the outlet mixture, was also produced via
3
3
According to the reaction mechanism, the vapor-phase methylation of HFiP with DMC
obeys a co-operative action of acid-base pairs of the metal fluoride catalysts. The catalysts with
medium Lewis acidity and medium Lewis basicity (eg. MgF
adsorption of DMC and HFiP but also the desorption of the products, and thus exhibit the
highest activity. In the case of a catalyst with very strong Lewis acidity (eg. AlF ), its adsorption
to the carbonyl oxygen of DMC would be too strong, which would “poison” its activity [33]. On
the contrary, if the basicity of the catalyst was strong (eg. BaF and SrF ), the catalyst would also
be “poisoned” by the hardly reversible adsorption of acid molecules like CO or even HFiP itself
34].
2
and CaF
2
) promote not only the
3
2
2
2
[
Notably, although both MgF
2
and CaF
2
show medium Lewis acidity and medium Lewis
(2.01
(1.61 mmol h m ) is probably due to the larger total amount of Lewis
basicity, they exhibit different catalytic activity (Table 1). The higher activity of MgF
2
1
2
1
2
mmol h m ) than CaF
2
1
1
acid sites of MgF (66.1 mmol g ) than CaF (19.5 mmol g ) (Table 3). Since Lewis acid sites
2
2
play an important role in absorbing the DMC molecules and promoting the methylation reaction,
it’s easy to understand that a larger amount of medium Lewis acid sites represents higher activity
of the catalyst
4
. Conclusions
A novel and efficient vapor-phase synthetic approach to prepare HFE-356mmz was
demonstrated by utilizing metal fluorides as the catalysts in the methylation reaction of HFiP for
the first time. The catalysts enabled 100% selectivity of HFE-356mmz since no by-product from
1
8

HFiP was produced. All the other by-products from the methylation reagent (DMC) are volatile,
making the reaction solvent-free. Through systematic investigation of a series of metal fluorides
(
AlF
3
, MgF
2
, CaF
2
, SrF
2
, and BaF ), it was found that the activity of the catalyst was influenced
2
by the strength of both Lewis acidity and Lewis basicity of the surface of the catalyst. This is
because the two reactants, HFiP and DMC, were activated by the Lewis base sites and Lewis
acid sites of the catalysts, respectively. As a result, MgF with medium Lewis acidity and
2
medium Lewis basicity, as well as a large amount of Lewis acid sites, exhibits the highest
activity, which allows a very high conversion of HFiP (94.3%) in the methylation reaction. In
addition, MgF exhibits excellent stability and activity in 1000 hours. The significance of this
2
study is four-fold. First, it provides a novel strategy for the synthesis of HFE-356mmz, the
mechanism of which was clearly elucidated. Second, it paves the way for industrial production of
HFE-356mmz because the synthetic process is solvent-free, pollution-free, and continuous.
Third, it demonstrates a successful attempt of utilizing metal fluoride as catalyst in the
methylation reaction, which expands the application of metal fluorides. Fourth, the synthetic
strategy may be extended to other methylation reactions in future.
Declaration of Competing Interest
The authors declare no competing financial interest.
Acknowledgments
The authors are grateful to the financial support by Sinochem, Lantian (grant no.
ZHLT2015AC20).
1
9

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