Metal-free and base-free decarboxylation of substituted cinnamic acids in a deep eutectic solvent

Article abstract of DOI:10.1080/00397911.2019.1708945

A metal-free and base-free strategy was developed in DES to synthesize styrenes for the first time by decarboxylation of cinnamic acid derivatives, which provided a renewable and cost efficiently protocol to access various styrenes including those with functional groups such as 4-vinylphenol and 1-chloro-4-vinylbenzene.

Full text of DOI:10.1080/00397911.2019.1708945

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
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Metal-free and base-free decarboxylation of
substituted cinnamic acids in a deep eutectic
solvent
Wen-Bing Sheng, Yasmin Sumera, Chen Chen, Ming Zhang, Yuxin Lei, Caiyun
Peng, Bin Li, Yuqing Jian & Wei Wang
To cite this article: Wen-Bing Sheng, Yasmin Sumera, Chen Chen, Ming Zhang, Yuxin Lei,
Caiyun Peng, Bin Li, Yuqing Jian & Wei Wang (2020): Metal-free and base-free decarboxylation
of substituted cinnamic acids in a deep eutectic solvent, Synthetic Communications, DOI:
10.1080/00397911.2019.1708945
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SYNTHETIC COMMUNICATIONSV
https://doi.org/10.1080/00397911.2019.1708945
Metal-free and base-free decarboxylation of substituted
cinnamic acids in a deep eutectic solvent
Wen-Bing Shenga, Yasmin Sumerab, Chen Chena, Ming Zhanga, Yuxin Leia,
Caiyun Penga, Bin Lia, Yuqing Jiana, and Wei Wanga
aTCM and Ethnomedicine Innovation & Development International Laboratory, Academician
Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, Innovative Materia Medica
Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, PR China;
bHEJ, Research Institute of Chemistry, International Center for Chemical and Biological Sciences,
University of Karachi, Karachi, Pakistan
ABSTRACT
ARTICLE HISTORY
Received 6 August 2019
A metal-free and base-free strategy was developed in DES to synthe-
size styrenes for the first time by decarboxylation of cinnamic acid
derivatives, which provided a renewable and cost efficiently protocol
to access various styrenes including those with functional groups
such as 4-vinylphenol and 1-chloro-4-vinylbenzene.
KEYWORDS
Base-free; decarboxylation;
deep eutectic solvent;
metal-free; substi-
tuted styrene
GRAPHICAL ABSTRACT
Introduction
Styrene and its derivatives have gained particular attention due to widespread applications
in polymer industry, starting materials for fine chemicals and intermediates for bio-active
compounds.[1–3] Some of them possess bio-activities such as antioxidant, antibacterial,
antifungal, hypolipidemic, antimutagenic, and have been used as preventive agents.[4–7]
Increasing demands for styrenes owing to their simple structure and wide applications
have led to the development of several synthetic methodologies. Moreover, cinnamic acid
and its derivatives are one of the most widely used substrates in chemical synthesis
because of their bioavailability from natural and commercial sources. After the first report
from Goossen’s group[8–10] about decarboxylation of cinnamic acid for biaryl synthesis
CONTACT Wei Wang
wangwei402@hotmail.com; Caiyun Peng
paudy@126.com
TCM and Ethnomedicine
Innovation & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine
Research Center, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese
Medicine, Changsha, PR China.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
ß 2020 Taylor & Francis Group, LLC

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W.-B. SHENG ET AL.
Table 1. Optimization of reaction conditions.a
No.
Solvent (v/v)
T (ꢀC)
t (h)
Yield (%)b
1
2
3
4
5
6
7
8
DES
NMP
DMF
130
130
130
130
130
140
150
160
140
140
140
140
2
2
2
2
2
2
2
2
3
4
5
4
60
trace
0
DMSO
DES/NMP (1:1)
DES
DES
DES
DES
DES
DES
DES/M. S.
0
49
70
68
57
79
85
74
82
9
10
11
12
aUnless otherwise noted, the reaction conditions were as below, 1a 1 mmol, 4 ml DES.
bIsolated yields based on 1a.
using Cu/Pd catalytic system, decarboxylation strategy was followed by many other
groups, including acid-catalyzed,[11,12] base-catalyzed,[13–15] or transition metal (such as
Cu, Pd, Au, Ag) catalysed[2,16–18] for decarboxylation of cinnamic acid and its derivatives.
It is a grace reaction but with the faulties of high reaction temperature, long reaction
time and harmness to environment caused by the solvent and transition metal catalyst.
Deep eutectic solvents (DES) is a new family of ionic fluids with the character of
availability, non-toxicity, biodegradability and low price, and recently it has attracted
considerable attention especially in the fields of catalysis and synthesis.[19–24] Inspired
by recent reports that DES can be used to dissolve CO2, and compared to the harsh
conditions of decarboxylation, we envision a DES-based strategy which could be applied
to decarboxylation of cinnamic acid. 4-Hydroxycinnamic acid was heated at 140 ꢀC1 in
DES and then generated corresponding styrene in moderate yields [Eq. (1)]. Compared
to conventional decarboxylation methodology, DES enabled cinnamic acid to decarb-
oxylate with metal-free and base-free in moderate to good yields.
(1)
Results and discussion
To study the decarboxylation reaction, we started screening the reaction temperature,
time, and different solvents for the decarboxylation of cinnamic acid 1, the tested condi-
tions are summarized in Table 1. When 4-hydroxycinnamic acid 1a was heated in DES
at 130 ꢀC for 2 h, 4-vinylphenol 2a, the decarboxylation product was obtained with 60%
1The reaction temperature is not corrected in this job, and it was 118 ꢀC after corrected.

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3
Table 2. Decarboxylation of different aromatic carboxylic acid in DES.a
Entry
R
Product
Yieldb/%
1
2
3
4
5
6
7
8
4-OHC6H4–CH ¼ CH–(1a)
3-OHC6H4–CH ¼ CH–(1b)
C6H5–CH ¼ CH–(1c)
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
85
N.D.
65
68
70
68
65
62
N.D.
<5%
71
73
<5%
<5%
4-CH3C6H4–CH ¼ CH–(1d)
4-ClC6H4–CH ¼ CH–(1e)
4-NO2C6H4–CH ¼ CH–(1f)
3-CH3C6H4–CH ¼ CH–(1g)
3-ClC6H4–CH ¼ CH–(1h)
3-NO2C6H4–CH ¼ CH–(1i)
3-CH3OC6H4–CH ¼ CH–(1j)
2-CH3C6H4–CH ¼ CH–(1k)
2-ClC6H4–CH ¼ CH–(1l)
2-NO2C6H4–CH ¼ CH–(1m)
2-CH3OC6H4–CH ¼ CH–(1n)
9
10
11
12
13
14
15
2o
71
74
(
1o
)
16
2p
(
(
1p
)
)
17
18
2q
2r
78
75
1q
3,4,5-trihydroxyphenyl–(1r)
aUnless otherwise noted, the reaction conditions were as below,1 mmol substrate, 4 ml DES, heated at 140 ꢀC for 4 h.
bIsolated yield based on 1.
yield base on 1a. The desired product 2a was obtained with 85% isolated yield when
the reaction temperature was increased to 140 ꢀC and time extended 4 h. Changed the
solvent to NMP, and only a trace of 2a was observed, while there was no product was
detected in DMF, or in DMSO under the same conditions (Table 1, entries 2–4). The
reaction temperature and time had great influence on the reaction (Table 1, entries
6–11). In addition, the inert gas such as N2 in the reaction did not affect the reaction
compared with air. The controlled experiment also showed that the molecular sieves did
not affect to the decarboxylation. On the basis of these results, we decided to set heating
at 140 ꢀC for 4 h in DES under air atmosphere as the standard reaction condition.
Under the optimized reaction conditions, then the scope and limitation of this reac-
tion were examined. The results were summarized in Table 2. Cinnamic acid and its
derivatives including 4-hydroxycinnamic acid (1a) gave good yield at 140 ꢀC (Table 2,
entry 1) whereas 3-hydroxycinnamic acid did not afford the styrene product (Table 2,
entry 2) as meta-substitution need higher temperature than para-substituted cinnamic
acid.[25] Thus, the cinnamic acid bearing electron-donating groups like alkyl, and
hydroxy groups on benzene ring decarboxylated readily, produced the corresponding

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W.-B. SHENG ET AL.
Table 3. Renewability of DES for decarboxylation of 4-hydroxycinnamic acid.
No. Recycle
Yield (%)
1
2
3
4
5
85
70
60
46
28
Figure 1. The plausible mechanism of decarboxylation.
vinylbenzenes in high yields (Table 2, entries 1, 4, 7, 11), meanwhile 4-vinylphenol was
obtained in 85% yield and no polymer was detected in the standard condition. No 4-
vinylphenol product was isolated due to the polymerization in reference [2], in another
words, DES was an effective retardant for the polymerization. Cinnamic acid bearing
methyl and chlorine at the meta, ortho and para positions afforded the desired products
(Table 2, entries 1, 4, 5, 7, 8, 11, 12). It is a pity that the substituents of nitryl and
methoxy at the meta and ortho positions did not tolerate the conditions (Table 2,
entries 9, 10, 13 and 14). At the same time, heterocyclic aromatic acid such as benzo-
furan-2-carboxylic acid, 1 H-indole-2-carboxylic acid and benzo[b]thiophene-2-carbox-
ylic acid were checked in the similar condition, they could run smoothly and the
desired product got more than 71% isolated yield (Table 2, entries 15–17). Gallic acid
also ran smoothly under the same condition (Table 2, entry 18).
The transformation value was further displayed by synthesis of 4-vinylphenol in
gram scale. Thus, employing 10 mmol 4-hydroxycinnamic acid (1a) decarboxylated in
10 mL DES under 140 ꢀC for 5 h, 4-vinylphenol (2a) was achieved readily in 80%
isolated yield.
In addition, the renewability of DES was evaluated by decarboxylation of 4-hydroxy-
cinnamic acid for five times. The results were summarized in Table 3, which showed
that DES was reusable in the standard condition, and there is some loss in activity of
DES after reused five times. The reason is that urea in the DES occurred a slight
decomposition of near 100 ꢀC.[26]
DES showed basic properties with basicity value of 10.86[27,28] which is more than
the compared nitrogen base used and basicity value required for decarboxylation reac-
tion, i.e., pKa ꢁ7.[5] Polarity, basic property and ability to dissolve CO2 lead to the
interesting results observed for the synthesis of styrene for the first time.
Base on the results of the current study and the reported references,[8,18,29] the plaus-
ible mechanism was shown as Figure 1. The proposed mechanism of the decarboxyl-
ation was as follows, quaternary ammonium was combined with carboxylic acids
through ionic bond, then CO2 was given out and styrene was obtained.

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5
Conclusions
In summary, we have developed a metal-free and base-free decarboxylation procedure
for the synthesis of substituted vinylbenzene including those bearing functional groups
from bio-sourced and readily available cinnamic acid derivatives using DES as a solvent
for the first time. This method is extremely renewable and cost efficient, and it can also
run smoothly in gram scale.
Experimental
All the chemicals and solvents were purchased from Aladdin reagent and used without
any further purification unless indicated otherwise. All products were characterized by
1H NMR, 13C NMR, and mass spectra (EI). 1H NMR spectra were recorded on
600 MHz in CDCl3, and 13C NMR spectra were recorded on 150 MHz in CDCl3 using
1
TMS as internal standard. Copies of H NMR and 13C NMR spectra are provided as
Supporting Information.
Typical procedure for the decarboxylation of substituted cinnamic acids in a deep
eutectic solvent
A 20-mL test tube equipped with magnetic stirring bar was charged with 1 mmol substi-
tuted cinnamic acid and 5 ml DES, heated at 140 ꢀC in an oil bath for 4 h. After the
mixture was cooled to room temperature, extracted with ethyl acetate (3 ꢂ 15 mL), com-
bined, and evaporated under vacuum. Pure product was obtained by silica gel column
chromatography with PE and ethyl acetate. All the compounds, after purification, were
weighted and characterized by MS, 1H NMR, 13C NMR. All the products are
known compounds.
1
Full experimental details of H and 12C NMR spectra can be found in the supplemen-
tary material.
Funding
This work was supported by the Key Research and Development Programs of Hunan Science
and Technology Department (2018SK2113, 2018SK2119 and 2018WK2081), Administration of
Traditional Chinese Medicine of Hunan Province scientific research project (2018-57),
Pharmaceutical Open Fund of Domestic First-class Disciplines (cultivation) of Hunan Province
(2018YX02) and Undergraduate research-based learning and innovative experimental project of
Hunan University of Chinese Medicine (2018-43).
ORCID
Wei Wang
http://orcid.org/0000-0003-0876-2205
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