Cyanide-Free One-Pot Synthesis of Methacrylic Esters from Acetone

Article abstract of DOI:10.1002/chem.201901933

Methacrylic esters, represented by methyl methacrylate (MMA), are widely used as commodity chemicals. Here, the one-pot synthesis of methacrylic esters from acetone, a haloform and alcohols in the presence of an organic base is described. Using DBU as the organic base for the reaction of acetone, chloroform and methanol in acetonitrile afforded MMA in 66 % yield. When the solvent was replaced by benzonitrile, the product MMA was successfully purified by distillation. Applicability of this process to various alcohols was also investigated to show ethyl, phenyl, CF₃CH₂, and n-C₆F₁₃CH₂CH₂ esters were obtained in moderate yields. The use of bromoform instead of chloroform resulted in the improvement of the yield, for example, methyl and n-C₆F₁₃CH₂CH₂ esters up to 81 and 70 %, respectively. The reaction with deuterated starting materials acetone-d₆ and MeOH-d₄, with DBU in acetonitrile afforded deuterated MMA (MMA-d₈) in 70 % yield.

Full text of DOI:10.1002/chem.201901933

A Journal of
Accepted Article
Title: Cyanide Free One-pot Synthesis of Methacrylic Esters from
Acetone
Authors: Minoru Koyama, Takafumi Kawakami, Takashi Okazoe, and
Kyoko Nozaki
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201901933
Link to VoR: http://dx.doi.org/10.1002/chem.201901933
Supported by

10.1002/chem.201901933
Chemistry - A European Journal
FULL PAPER
Cyanide Free One-pot Synthesis of Methacrylic Esters from
Acetone
Minoru Koyama,[a] Takafumi Kawakami,[a] Takashi Okazoe,*[a,b] and Kyoko Nozaki*[a]
Dedication ((optional))
Abstract: Methacrylic esters, represented by methyl
methacrylate (MMA), are widely used as commodity chemicals.
Here we present the one-pot synthesis of methacrylic esters from
acetone, haloroform and alcohols in the presence of an organic
base. Employing DBU as the organic base for the reaction of
acetone, chloroform and methanol in acetonitrile afforded MMA in
66% yield. When the solvent was replaced by benzonitrile, the
product MMA was successfully purified by distillation. Applicability
of this process to various alcohols was also investigated to show
ethyl, phenyl, CF3CH2, and n-C6F13CH2CH2 esters were obtained
in moderate yields. The use of bromoform instead of chloroform
resulted in the improvement of the yield, e.g. methyl and n-
C6F13CH2CH2 esters up to 81 and 70%, respectively. The reaction
with deuterated starting materials, acetone-d6 and methanol-d4,
with DBU in benzonitrile afforded deuterated MMA (MMA-d8) in
70% yield.
developed. In the C4 process (Scheme 1b), oxidation of
isobutylene via methacrolein provides methacrylic acid. MMA is
produced by the subsequent esterification with methanol. The
third process is the C2 process (Scheme 1c): First, methyl
propionate is made from ethylene, carbon monoxide, and
methanol. Subsequently, methyl propionate reacts with
formaldehyde and then dehydration results in the formation of
MMA.[4] As an alternative route to methacrylate esters, here we
propose the use of chloroform in place of hydrogen cyanide in
Scheme 1a as a C1 source. In 1948, Weizmann et al. reported
the
reaction
of
1,1,1-trichloro-2-methyl-propan-2-
ol(acetonechloroform, 2) with potassium hydroxide in alcohol to
form α-alkoxypropanoic acid 3 (Scheme 1d). Isolation of 3
followed by treatment with phosphorus pentoxide resulted in the
formation of methacrylic esters.[5] As shown above, all pathways
require multi-step operations.
Here we report, a one-pot synthesis of methacrylic esters 1
from acetone, haloroform, and alcohols (Scheme 1e). The use of
an organic base, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was
the key for our success. Given that haloform is easily available in
laboratory scale, this provides an effective synthetic pathway for
various methacrylate esters.
Introduction
Methacrylic esters are widely used as monomers for the
synthesis of variety of polymeric materials. Among them, methyl
methacrylate (MMA) is used for producing acrylic plastics
poly(methyl methacrylate) (PMMA), whose world production
reaches about 2.5 million metric tons,[1,2] and its demand
continues to increase year by year. Three representative
industrial synthetic processes of MMA are summarized in
Scheme 1a–c.[3] A process shown in Scheme 1a is the C3 process,
by which, currently 60% of MMA is industrially produced.[2] In the
first step, acetone and hydrogen cyanide are converted to
acetone cyanohydrin in the presence of a base. Secondly,
methacryl amide is formed in the presence of sulfuric acid.
Addition of methanol completes the process for the MMA
synthesis. The major drawbacks of this process could be the
formation of stoichiometric amount of ammonium bisulfate as a
waste. In order to avoid this problem, two new routes have been
[a]
Minoru Koyama, Dr. Takafumi Kawakami, Dr. Takashi Okazoe, and
Prof. Dr. Kyoko Nozaki
Department of Chemistry and Biotechnology
Graduate School of Engineering, The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan.
E-mail: t-okazoe@chembio.t.u-tokyo.ac.jp
nozaki@chembio.t.u-tokyo.ac.jp
Scheme 1. Synthetic methods of methacrylates: Current industrial processes
for MMA synthesis (a–c) versus the route from acetone, chloroform, and
alcohols (d and e).
Homepage: http://park.itc.u-tokyo.ac.jp/nozakilab/
Dr. Takashi Okazoe
[b]
Innovative Technology Research Center, AGC Inc.
1-1 Suehiro-cho, Tsurumi, Yokohama, 230-0045, Japan.
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/chem.201901933
Chemistry - A European Journal
COMMUNICATION
Results and Discussion
benzonitrile as the solvent (64% NMR yield, 35% isolated yield,
Table 2, entry 5), showing its potential application to a larger scale
synthesis.
First, equimolar amount of acetone and chloroform were mixed
with 3.0 equiv. of DBU in methanol (10 equiv.). After 96 h at 50°C,
chloroform was consumed in 82% conversion. The products were
analyzed by 1H NMR spectroscopy to show, while α-methoxyester
3a and the α-chloroester 4a were the major products (35% and
24% yield, respectively), the desired methacrylate ester 1a was
obtained in 5.4%(Table1, entry1). By optimizing the feed ratio
(entries 1–5), the yield of 1a was improved to 40% but α-
chloroester 4a remained as the major side product (entry 4). The
use of acetonitrile under reflux condition improved the conversion
of 4a to 1a albeit undesired side product 5[8] generated (entry 6).
By lowering the reaction temperature to 50 °C, we confirmed the
consumption of acetone in 18 h (entry 7). Accordingly, we carried
out the reaction first at 50 °C for 18 h and then heated additional
24 h under reflux to obtain 1a in 66% (Table 1, entry 8). Among
the examined solvents, acetonitrile and benzonitrile afforded 1a
in the higher yields (entries 8–12).
Table 2. Optimization of the reaction condition for the synthesis of methyl
methacrylate (1a) from acetone, chloroform, and methanol. [a]
Entry
1
Base
DBU
Conv (%)
100
1a (%)
66
3a (%)
6.5
4a (%)
14
2
Et3N
0.0
0.0
0.0
0.0
3[b]
t-Bu-P1
DBU, t-
Bu-P1
100
21
5.6
74
Table1. Optimization of the reaction condition for the synthesis of methyl
methacrylate (1a) from acetone, chloroform, and methanol in the presence
of DBU as base. [a]
4[c],[d]
5[e]
100
100
78
1.3
6.6
2.9
14
64
(35)[f]
DBU
[a] The yields of the products were determined by 1H NMR using 1,4-
dibromobenzene as an internal standard. [b] 5.0 mmol of chloroform was used.
[c] 2.5 mmol of chloroform was used. [d] First t-Bu-P1 (3.3 equiv.) 50 °C, 18 h
and then DBU (2.0 equiv.) reflux, 24 h. [e] 300 mmol of chloroform was used
and PhCN was in place of CH3CN as a solvent. [f] Isolated yield.
CHCl3
CH3CN
(mL)
1a
3a
4a
10
X
Y
Z
Conv.
(%)
Entry
The possible reaction mechanism shown in Scheme 2 nicely
explains the base effect. In 2000, Aggarwal et al. reported the
formation of acetonechloroform 2 from acetone and chloroform in
the presence of DBU.[9] It is likely that the same reaction took
place as the first step in our system. While subsequent elimination
of hydrogen chloride from 2 to form dichloroepoixide 6 was
proposed in literature,[10] direct formation of 6 by the reaction of
acetone with dichlorocarbene (:CCl2) might be another possibility.
Since triethylamine is a weaker base (pKBH = 18.63 in MeCN) than
DBU (pKBH = 24.16 in MeCN),[11] the deprotonation of chloroform
seems insufficient with triethylamine to retard the reaction (Table
1, entry 2). Subsequently, the reaction of 6 with methanol would
generate α-chloroester 4. In fact, Stick reported the reaction of
dialkyl(trichloromethyl)methanol R2C(CCl3)OH can be converted
(%)
(%)
(%)
(%)
1[a]
2[a]
1.0
1.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
10
3.0
3.0
3.0
3.0
3.0
3.3
3.3
3.3
3.3
3.0
3.0
3.3
82
87
5.4
37
39
40
36
48
16
66
29
18
25
55
35
16
24
14
36
37
40
17
59
14
19
32
13
9.4
0.0
0.3
1.4
1.3
2.6
11
3.5
3.5
2.5
2.0
2.5
2.5
2.5
2.5
2.5
2.5
2.5
3[a]
100
100
100
98
13
4[a]
8.3
5.3
2.9
5.7
6.5
2.7
0.9
1.3
6.5
5[a]
6[b]
5
5
5
8
8
8
5
7[c]
89
2.5
5.3
7.2
13
8[d]
100
88
9[d,e]
10[f,g]
11[f,h]
12[f,i]
76
87
14
to α-chloroesters in the presence of DBU and alcohols.[12]
A
100
6.2
[a] 50°C, 96 h. [b] reflux 24 h. [c] 50°C, 18 h. [d] 50°C, 18 h; then reflux,
proposed reaction mechanism in literature for the conversion of 6
to 4 is drawn as A in Scheme 2: addition and elimination of
chloride take place spontaneously accompanied by the ring
opening of epoxide. α-Alkoxyester 3, which was the exclusive
product by using potassium hydroxide as a base (Scheme 1d),
was a minor product in all entries in Table 1. With an organic base,
DBU for example, the chloride anion of the neutralized HCl
remains in solution, unlike the inorganic base form insoluble salts
such as KCl. Assuming that the selectivity to α-chloroester 4 over
α-alkoxyester 3 originates from the nucleophilic species, either
chloride or alkoxide in mechanism A, the higher concentration of
the chloride anion with organic base could be the origin of the
selective formation of 4 in this study. For the last step, the
24 h. [e] CHCl3, 2.5 mmol. [f] 50°C, 18 h; then 80°C, 24 h. [g] 1,4-dioxane
as a solvent. [h] diglyme as a solvent. [i] PhCN as a solvent.
Among the organic bases examined in this study, the highest
yield was detected with DBU. With triethylamine, no reaction was
observed (Table 2, entry 2). On the other hand, with phosphazene
t-Bu-P1, the yield of 1a was lower (21%), and a significant amount
of α-chloroester 4a (74% yield) was produced (Table 2, entry 3).
By the sequential addition of t-Bu-P1 and then DBU, the yield of
1a was elevated up to 78% (Table 2, entry 4). Purification of the
product MMA was accomplished by distillation by using
This article is protected by copyright. All rights reserved.

10.1002/chem.201901933
Chemistry - A European Journal
COMMUNICATION
dehydrochlorination of α-chloroester 4 was successfully mediated
by a base, especially by DBU.[13] This is contrastive to the reaction
in Scheme 1d, which required the use of acidic conditions to
eliminate methanol from α-alkoxyester 3. Notably, DBU is known
to be a uniquely efficient base for the elimination of hydrogen
chloride.[14] Although phosphazene t-Bu-P1 is a stronger base
(pKBH = 26.88 in MeCN)[11] than DBU, DBU shows higher activity
for the dehydrochlorination of 4 to form methacrylate 1. In fact,
dehydrochlorination of 4 to 1 proceeded in a quantitative
conversion with DBU. The reaction resulted in a low conversion
with t-Bu-P1 under the same conditions (see Supporting
Information).
Br can be accelerated. More importantly, it is advantageous for
the dehydrohalogenation form 4a-Br compared to 4a. This shows
good consistency with the absence of α-bromoester 4a-Br in the
crude mixture (see Supporting Information). The use of iodoform
resulted in lower conversion due to the lower solubility in
acetonitrile.
Table 3. Synthesis of methacrylic esters (1a–f) from various alcohols.[a]
entry
R
Et
i-Pr
Ph
CF3CH2
n-C6F13
(CH2)2
Conv. (%)
1 (%)
46
8.6
31
4 (%)
25
10
58
8.6
1
2
3
4
97
94
97
100
50
[b]
5
79
8.8
[a] The reaction was carried out under the same conditions as entry 2 in Table
1 by varying the alcohol. [b] Not identified.
Scheme 2. Possible reaction mechanism for the one-pot formation of
methacylic ester in this study.
In addition to methanol, the reaction was applicable to other
alcohols. Under the same conditions as MMA was obtained in
66% (entry 1 in Table 2), the reaction was examined with several
alcohols, and the results are summarized in Table 3. From ethanol,
ethyl methacrylate 1b was obtained in 46% yield along with 25%
of α-chloroester 4b (entry 1). The reaction was susceptible to
steric repulsions thus the conversion stayed low for i-PrOH (entry
2). With PhOH, the major product was α-chloroester 4d (58%
yield) (entry 3). The lower conversion from 4d to 1d may be
attributed to the higher acidity of PhOH (pKa 9.95), which would
have humpered the deprotonation of 4d by DBU.[15a] With 2,2,2-
trifluoroethanol (pKa 12.4), the corresponding methacrylate 1e
was given in a comparable yield (50%) to that of ethanol (pKa
15.9) (entry 4).[15b] The much lower yield of 1f starting from ethanol
bearing a perfluoroalkyl group at the 2-position of alcohol (entry
5) may be attributed to the undesirable elimination of methacrylic
acid from 1f because the formation of terminal alkene n-
C6F13CH=CH2 was confirmed in 38% yield.
Figure 1. The use of bromoform and its application to other carbonyl
compounds.
The reactant carbonyl compound was not limited to acetone
(Figure 1). Cyclohexanone was successfully converted to
cyclohexenecarboxylic ester 7a in 87% yield.[17] Regarding to
acetophenone, the product was a complex mixture, and the
desired α-phenyl acrylate 8a was not obtained. Aldehydes, such
as isobutyraldehyde and benzaldehyde were converted to the
corresponding α,β-unsaturated esters 9a and 10a in 22% and
53% yields, respectively. Notably, by using bromoform,
perfluoroalkyl-group was successfully incorporated to form
methacrylate 1f in 70% yield, which is contrastive to the low yield
with chloroform (entry 5 in Table 2). The higher yield may be
attributed to the much lower reaction temperature in case for
bromoform compared to that for chloroform, that suppressed the
undesired elimination of methacrylic acid.
For small scale synthesis, the use of bromoform in place of
chloroform was proven to be far more effective. From bromoform,
methyl methacrylate (1a) was obtained in 81% yield at 25 °C in 5
h (Figure 1), the value being superior to 66% yield from chloroform
at 50°C for 18 h and then reflux for 24 h (entry 1 in Table 2). The
higher activity of bromoform may be attributed to its higher acidity
(pKa of chloroform 15.5, bromoform 13.7).[16] Facile deprotonation
accelerates the formation of dibromoepoxide, 6-Br (analogous to
6 in Scheme 2). Bromide is also a better leaving group than
chloride in acetonitrile so that the isomerization from 6-Br to 4a-
This article is protected by copyright. All rights reserved.

10.1002/chem.201901933
Chemistry - A European Journal
COMMUNICATION
The reaction was successfully applied to the synthesis of
deuterated methyl methacrylate (MMA-d8). As shown in Scheme
3, the reaction of acetone-d6, bromoform, and methanol-d4
afforded MMA-d8 (1a-d8) in 70% yield (analyzed by GC).[18] In this
cases, the yield of 1a-d8 was lower compared to the non-
deuterated MMA (1a). In the reactions (Scheme 3), longer
reaction time and heating was needed for full conversion of -
bromoester 4a-Br-d9 (See Supporting information for details).
This may correspond that the elimination of hydrogen bromide
from 4a-Br-d9 was slower than that from 4a-Br because a C–D
bond is stronger than a C–H bond. The polymer of deuterated
MMA is known to be a promising material for optical waveguide
owing to its transparency in the region of absorption due to C–H
bonds. [19]
Works Co. FR 64-4-C. Benzonitrile was purchased from TCI and dried with
MgSO4, filtered, and purified by distillation. Bromoform was purchased
from Kanto Chemical Co., Inc. (Kanto) and washed with H2O, and purified
by distillation over CaH2. Chloroform, which is stabilized by amylene, was
purchased from Kanto and used as received. 4a was recieved from AGC
Inc. and used as recieved. All other materials were purchased from Kanto,
Wako Pure Chemical Industries, Ltd., TCI, Aldrich and used as received.
Representative procedure for the one-pot synthesis of MMA (1a) (Table 1,
entry 7): To a solution of acetone (2.90 g, 50 mmol), DBU (5.02 g, 33 mmol)
and methanol (0.801 g, 25 mmol) in acetonitrile (5.0 mL) and 1,4-
dibromobenzene (internal standard, 0.150 g, 0.64 mmol) was slowly added
chloroform (1.19 g, 10 mmol) at 0 °C and the mixture was stirred for 18
hours at 50 °C. Then the mixture was warmed to the reflux condition and
kept stirred for further 24 hours. After cooling to ambient temperature, the
yield of 1a was determined by 1H NMR using 1,4-dibromobenzene as
internal standard (6.6 mmol, 66%).
Optimization of the reaction conditions was carried out as shown below by
varying the reaction temperature and time, concentration, and the
equivalence of acetone, methanol, and DBU to chloroform. In some entries,
the DBU adduct 10 was produced as a side product.
Scheme 3. Synthesis of deuterated MMA (1a-d8)
Conclusions
1
5: H NMR (500 MHz, DMSO-d6) δ; 3.29–3.26 (m, 2H), 3.24–3.21 (t, J =
In conclusion, methacrylic esters were synthesized in one-pot
from acetone, chloroform, and various alcohols using acetonitrile
or benzonitrile as a solvent. The reaction is also applicable to
bromoform and other carbonyl compounds. Deuterated methyl
methacrylate (MMA-d8) was easily produced. We believe, the
reaction described here provides a new synthetic route for MMA
production from easily available starting materials.
5.5 Hz, 2H), 3.10–3.07 (t, J = 5.5 Hz, 2H); 2.18–2.16 (m, 2H), 1.97–1.92
(quin, J = 6.0 Hz, 2H), 1.78–1.73 (m, 2H), 1.58–1.51 (quin, J = 6.0 Hz, 2H),
1.01 (s, 6H); 13C NMR (126 MHz, DMSO-d6) δ; 193.3, 165.9, 89.1, 63.4,
52.6, 48.3, 35.9, 28.4, 26.0, 22.0, 21.8, 20.7; HRMS(ESI) [M + Cs]+ Calcd
for C13H20CsN2O 353.0625. Found 353.0640.
Large scale synthesis and isolation of MMA (1a) (Table 2, entry 5): To a
solution of acetone (110 mL, 1.5 mol), DBU (145 mL, 0.99 mol) and
methanol (30 mL, 0.75 mol) in benzonitrile (150 mL) and 1,4-
dibromobenzene (0.979 g, 4.15 mmol), was slowly added chloroform
(35.80 g, 0.30 mol) at 0 °C and the mixture was stirred for 18 hours at
50 °C. Then the mixture was warmed to 80°C and keep stirred for further
24 hours. After cooling to ambient temperature, the yield of methyl
methacrylate was determined by 1H NMR using 1,4-dibromobenzene as
internal standard (0.19 mmol, 64%). After three distillations (first: simple
distillation to separate DBU and its salt, second and third: precise
distillation with fractionating column), 1a was isolated (10.4 g, 35% yield,
>99% pure by GC).
Experimental Section
General: All manipulations were carried out using standard Schlenk
techniques under N2 purified by passing through a hot column packed with
BASF catalyst R3-11.NMR spectra were recorded on JEOL JNM-ECS400
(1H: 400 MHz, 13C: 101 MHz), Bruker Ascend 500 (1H: 500 MHz, 13C: 126
MHz) NMR spectrometers, or JEOL ECZ-400 (1H: 400 MHz). 1H NMR
analyses were performed in dimethylsulfoxide-d6 with the number of FID's
collected per sample of 16–128. Chemical shift values for protons are
referenced to the residual proton resonance of dimethylsulfoxide-d6 (δ
2.49). 13C NMR analyses were performed in dimethylsulfoxide-d6 with the
number of FID's collected per sample of 1024–2048. Chemical shift values
for carbons are referenced to the carbon resonance of dimethylsulfoxide-
d6 (δ 39.52). High-resolution mass (HRMS) spectra were taken on a JEOL
JMS-T100LP mass spectrometer with the electron spray ionization time-
of-flight (ESI-TOF) method. GC analysis was performed by Agilent
Technologies 7890B equipped with DB-1301 capillary column (0.250 ID,
1.00 μm df, 30 m). Karl Fischer titration was performed by Mitsubishi
One-pot synthesis of α,β-unsaturated esters from bromoform: To a
solution of carbonyl compound (5.0 equiv.), DBU (4.5 equiv.), and
methanol (1.5 equiv.) in acetonitrile (1.3 mL) and 1,4-dibromobenzene,
was slowly added bromoform (2.5 mmol, 1.0 equiv.) at 0 °C and the
mixture was stirred for ambient temperature (Warning: This reaction is
exothermic; water bath is necessary to control the reaction) at 5 hours. The
yield of the corresponding methacrylate was determined by 1H NMR
analysis using 1,4-dibromobenzene as internal standard.
Chemical
Analytech
CA-21
equipped
with
AQUAMICRON
AX/CXU.Distillation of 1a (MMA) was performed with Kiriyama Glass
This article is protected by copyright. All rights reserved.

10.1002/chem.201901933
Chemistry - A European Journal
COMMUNICATION
[5]
(a) Ch. Weizmann, M. Sulzbacher, E. Bergmann, J. Am. Chem. Soc.
1948, 70, 1153–1158. (b) T. Fujita, S. Wada, T. Okazoe, K. Murata
(Asahi Glass Co., Ltd.), WO2014038489A1, 2014. (c) T. Fujita, K. Murata,
N. Shirota, Y. Suzuki, D. Jomuta (Asahi Glass Co., Ltd.),
WO2015005243A1, 2015.
One-pot synthesis of deuterated MMA (1a-d8): To a solution of acetone-d6
(5.0 equiv.), DBU (3.3 equiv.) and methanol-d4 (2.5 equiv.) in benzonitrile
was slowly added bromoform (10 mmol = 1.0 equiv.) at 0 °C and the
mixture was stirred for 24 hours at ambient temperature and then at 50°C
for 24 h. After cooling to ambient temperature, the yield of the
corresponding methacrylate was determined by GC analysis using
benzene as an internal standard (70% yield).
[6]
[7]
(a) I. Mochida, H. Watanabe, A. Uchino, H. Fujitsu, K. Takeshita, J. Mol.
Catal. 1981, 12, 359–364. (b) J. E. Taylor, M. D. Jones, J. M. J. Williams,
S. D. Bull, Org. Lett. 2010, 12, 5740–5743.
(a) K. Iwanaga, K. Seki, T. Hibi, K. Issoh, T. Suzuta, M. Nakada, Y. Mori,
T. Abe, in R&D Report, “SUMITOMO KAGAKU”, Sumitomo Chemical
Co.,
Ltd.
2004,
1,
4–12.
(https://www.sumitomo-
Determination of the deuterated ratio: The measurement was carried using
a reference solution prepared from 111.8 mg of C6H6 in 2.9285 g of DMSO-
d6. To a portion of transferred mixture containing 1a-d8 (214 mg, containing
5.5 mg of 1a-d8 based on GC analysis), was added the solution of benzene
in DMSO-d6 (667.1 mg, containing 24.5 mg of benzene). By 1H NMR
analysis, the deuterated ratio was determined comparing the integration of
each peak of 1a-d8 with that of C6H6.
chem.co.jp/english/rd/report/files/docs/20040100_p0e.pdf) (b) M. T.
Holbrook in Kirk‐Othmer Encyclopedia of Chemical Technology, John
Wiley&Sons, Inc., 2003, 6, pp. 279–290.
[8]
[9]
See supporting information for details for the formation of 5.
V. K. Aggarwal, A. Mereu, J. Org. Chem. 2000, 65, 7211–7212.
[10] (a) W. Reeve, J. R. McKee, R. Brown, S. Lakshmanan, G. A. McKee,
Can. J. Chem. 1980, 58, 485–493. (b) M. Mahdavi, M. Asadi, M. Saeedi,
Z. Rezaei, H. Moghbel, A. Foroumadi, A. Shafiee, Synlett 2012, 23,
2521–2525. (c) Z. Li, M. K. Gupta, T. S. Snowden, Eur. J. Org. Chem.
2015, 7009–7019.
[11] T. Rodima, I. Kaljurand, A. Pihl, V. Mäemets, I. Leito, I. A. Koppel, J. Org.
Chem. 2002, 67, 1873–1881.
[12] A. Scaffidi, B. W. Skelton, R. V. Stick, A. H. White Aust. J. Chem. 2006,
59, 426–433.
Acknowledgments
[13] Dehydrochlorination of α-chloroester 4 in the presence of FeCl3 as Lewis
acid catalyst was reported. H. J. Barrett (E. I. Du Pont de Nemours &
Company), US2013648A, 1935.
We are grateful to Prof. Takanori Iwasaki (University of Tokyo) for
helpful discussions.
[14] H. Oediger, F. Möller, K. Eiter, Synthesis 1972, 591–598.
[15] The pKa for phenol (pKa = 10.0) is more acidic than 2,2,2-trifluoroethanol
(pKa = 12.4). (a) For phenol, M. Ahmad, A. L. Teel, R. J. Watts Environ.
Sci. Technol. 2013, 47, 5864–5871. (b) For 2,2,2-trifluoroethanol, D.
Donghi, T. Beringhelli, G. D’Alfonso, M. Mondini Chem. Eur. J. 2006, 12,
1016–1025.
Keywords: Methacrylic ester • Acetone • Chloroform • DBU •
one-pot synthesis
[1]
M. J. D. Mahboub, J.-L. Dubois, F. Cavani, M. Rostamizadeh, G. S.
Patience Chem. Soc. Rev. 2018, 47, 7703–7738.
[16] K. J. Klabunde, D. J. Burton, J. Am. Chem. Soc. 1972, 94, 5985–5990.
[17] Synthesis of 1-cyclohexenecarboxylic acid was reported. V. D. Vitnik , M.
D. Ivanović , Ž. J. Vitnik , J. B. Đorđević , Ž. S. Žižak , Z. D. Juranić & I.
O. Juranić, Syn. Commun. 2009, 39, 1457–1471.
[2]
[3]
T. Degman, Focus on Catalysts 2018, 1, 1–2.
(a) K. Nagai Applied Catalysis A: General 2001, 221, 367–377. (b) H.
Sugiyama, U. Fischer, E. Antonijuan, V. H. Hoffmann, M. Hirao, K.
Hungerbühler Process Safety and Environmental Protection 2009, 87,
361–370. (c) J. Andraos ACS Sustainable Chem. Eng. 2016, 4, 312−323.
J. Gao, G. Fan, L. Yang, X. Cao, P. Zhang, F. Li, ChemCatChem 2017,
9, 1230–1241.
[18] The use of chloroform or chloroform-d in place of bromoform afforded
lower yield of 1a-d8. See supporting information for details.
[19] T. Kaino, K. Jinguji, S. Nara, Appl. Phys. Lett. 1983, 42, 567–569.
[4]
This article is protected by copyright. All rights reserved.

10.1002/chem.201901933
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
This article is protected by copyright. All rights reserved.