Synthesis of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates and cinnamates, monomers for side chain liquid crystal polymers

Article abstract of DOI:10.1007/s11164-016-2606-8

Abstract: A variety of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates and cinnamates, which can serve as monomers for side chain liquid crystal polymers, were readily synthesized from hydroquinone. Instead of the rare and expensive 2,5-dihydroxybenzaldehyde, ch

Full text of DOI:10.1007/s11164-016-2606-8

Res Chem Intermed (2017) 43:63–71
DOI 10.1007/s11164-016-2606-8
Synthesis of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates
and cinnamates, monomers for side chain liquid crystal
polymers
Yong Li1 Yao Yuan1 Yu-Guo Yang1
Zhi Li1
•
•
•
Received: 5 April 2016 / Accepted: 6 June 2016 / Published online: 1 July 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract A variety of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates and cinnamates,
which can serve as monomers for side chain liquid crystal polymers, were readily
synthesized from hydroquinone. Instead of the rare and expensive 2,5-dihydroxyben-
zaldehyde, cheaper and readily available hydroquinone was employed as starting
material in our new method. Hazardous reagents, such as highly flammable BH3.THF
employed in the reported literature, were excluded as well. Our new method uses
cheaper starting materials and chemicals, which are easier to handle with less safety
issues.
Graphical Abstract A variety of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates and cin-
namates, which can serve as monomers for side chain liquid crystal polymers, were
readily synthesized from hydroquinone. Instead of the rare and expensive 2,5-dihy-
droxybenzaldehyde, cheaper and readily available hydroquinone was employed as
starting material in our new method. Hazardous reagents, such as highly flammable
BH3.THF employed in the reported literature, were excluded as well. Our new method
uses cheaper starting materials and chemicals, which are easier to handle with less safety
issues.
Yong Li and Yao Yuan contributed equally to this work.
Electronic supplementary material The online version of this article (doi:10.1007/s11164-016-2606-
8) contains supplementary material, which is available to authorized users.
&
Zhi Li
zhili@bjtu.edu.cn
1
Department of Chemistry, School of Science, Beijing Jiaotong University, 3# Shangyuan Cun
Road, Haidian District, Beijing 100044, China
123

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Y. Li et al.
O
R'
OH
OH
O
O
O
R'
5 steps
RO
O
OR
O
R = Me, Et, n-Bu
R' = H, Me, Ph
Keywords 2,5-(4-alkoxybenzoyloxy)benzyl acrylates Á 2,5-(4-
alkoxybenzoyloxy)benzyl cinnamates Á Side chain liquid crystal polymers
Introduction
The 2,5-(4-alkoxybenzoyloxy)benzyl acrylates (Scheme 1A) are monomers of a
class of side chain liquid crystal polymers [1–3] (Scheme 1 B), which exhibit liquid
crystalline behaviour over a wide temperature range [3]. Many liquid crystalline
copolymers and elastomers can also be prepared by copolymerisation of the 2,5-(4-
alkoxybenzoyloxy)benzyl acrylates with other monomers [3].
The first synthesis of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates was reported by
Zhou et al. [1] in 1987 (Scheme 2). A modification was made by Davis et al. [3] in
1996 (Scheme 2).
As shown in Scheme 2, the starting material 2,5-dihydroxybenzaldehyde (1) is
rare and expensive. In step 2, it seems that the reduction of aldehyde 2 by NaBH4
(Zhou’s method [2, 3]) is not as successful as the authors claim [3]. Because instead
of NaBH4, BH3.THF (step 2, Davis’ method [3]) must be used for the reduction of
aldehyde 2. Otherwise the alcohol 3 can not be obtained while unexpected products
are formed [3]. The BH3.THF solution is highly flammable and sensitive to air or
moisture. It can react violently with water and may form explosive peroxides in
contact with air. As a result, Davis’ method would be hazardous. On the other hand,
insufficient information about the yields for preparation of aldehyde 2, alcohol 3,
and compound 4 was reported by the literature [1–3]. Only when R=Me and R0=H
the yields were given by both methods [1–3]. While R=Et or n-Bu, no yields were
reported [2] even if the compounds were fully characterized by 1H-NMR, elemental
analysis, and IR.
A
B
Scheme 1 Synthesis of side chain liquid crystal polymers from 2,5-(4-alkoxybenzoyloxy)benzyl
acrylates
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Synthesis of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates…
65
Scheme 2 Reported methods for synthesis of 2,5-(4- alkoxybenzoyloxy)benzyl acrylates
Scheme 3 Our synthesis route to 2,5-(4-alkoxybenzoyloxy)benzyl acrylates and cinnamates
123

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Y. Li et al.
Results and discussion
We reported herein a new method for the synthesis of 2,5-(4-alkoxybenzoy-
loxy)benzyl acrylates and cinnamates from cheap starting materials. The new
method uses chemicals which are easier to handle with less safety issues
(Scheme 3).
As shown in Scheme 3, 2-(hydroxymethyl)benzene-1,4-diol (5) can be obtained
in 59 % yield by the reaction of hydroquinone with excess paraformaldehyde in
xylene [4]. The starting materials are much more cheaper than the 2,5-dihydrox-
ybenzaldehyde (1) employed in the reported methods. Compound 5 can be prepared
on a multigram scale. After selective protection of the hydroxymethyl group of 5
with 3,4-dihydro-2H-pyran [5, 6] in the presence of pyridinium p-toluene-
sulphonate, 6 can be obtained in 50 % yield. Subsequently, we tried to synthesize
7. As shown in Scheme 4, two methods were employed for the synthesis of 7. It’s
worthy to noted that N,N0-Diisopropylcarbodiimide (DIC) has to be employed when
preparing 7b and 7c. 7 can be prepared in modest yield from 6.
With 7 in hand, we next tried to synthesize 3 by deprotection of the THP-group.
Mild reactions have to be employed in order to prevent hydrolysis of the two ester
groups of 7. CuSO4.5H2O [7, 8] was, therefore, employed for the THP-deprotection.
As shown in Scheme 5, 3 can be obtained in modest to good yields.
Finally, we tried to synthesize the monomer 2,5-(4-alkoxybenzoyloxy)benzyl
acrylates and cinnamates 4 from 3 with appropriate acid chloride [1–3].
As shown in Table 1, various 2,5-(4-alkoxybenzoyloxy)benzyl acrylates and
cinnamates 4 can be synthesized from 3 in the presence of Et3N (entries 1, 2, 3,
Table 1) or DMAP (entries 4, 5, 6, 7, Table 1) in good to excellent yields. The
alkoxy groups in 4 can be the butoxy group (entries 1, 2, 3, Table 1), ethoxy group
(entries 4, 5, 6, Table 1) or methoxy group (entry 7, Table 1). The groups attached
by in the olefinic bond of 4 can be only H atoms (entries 1, 4, Table 1), a methyl
group (entries 2, 3, 5, Table 1) or a phenyl group (entries 6, 7, Table 1). The methyl
group attached in the olefinic bond of 4 can be in the terminal of the olefinic bond
(entry 3, Table 1) or adjacent to the carbonyl group (entries 2, 5, Table 1). The
Scheme 4 Synthesis of 7 from 6
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Synthesis of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates…
67
Scheme 5 Synthesis of 3 by deprotection of 7
diverse monomers 4 could be employed for synthesis of versatile side chain liquid
crystal polymers.
In summary, a variety of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates and cinna-
mates 4 which could serve as monomers for side chain liquid crystal polymers were
readily synthesized from hydroquinone. Instead of the rare and expensive 2,5-
dihydroxybenzaldehyde, cheaper and readily available hydroquinone was employed
as starting material in our new method. Hazardous reagents such as highly
flammable BH3.THF employed in the reported literature were excluded as well. The
new method uses chemicals, which are easier to handle with less safety issues. The
preparation of monomers 4 on a multigram scale by our new method is under
research in our lab. This part of the work will be reported in due course.
Experimental
General
All commercially available reagents were used without further purification. Column
1
chromatography was performed on silica gel (200–300 mesh). H-NMR and 13C-
NMR spectra were recorded in CDCl3 or (CD3)2SO at 400 MHz on a Bruker NMR
spectrometer. All chemical shifts are reported in ppm downfield from TMS and
peak multiplicities are referred to as singlet (s), doublet (d), quartet (q), and
multiplet (m).
Synthesis of 5
2-(hydroxymethyl)benzene-1,4-diol (5) can be synthesized in 59 % yield by the
reaction of hydroquinone with excess paraformaldehyde in xylene according to the
reported method [4]. Compound 5 can be prepared on a multigram scale. IR (neat):
.
3752, 2840, 2368, 1728, 1704, 1648, 1620, 1524, 1332, 1288 cm-1 1H-NMR
((CD3)2SO): d 8.59 (s, 1H), 8.57 (s, 1H), 6.75–6.74 (m, 1H), 6.56–6.54 (m, 1H),
6.44–6.41 (m, 1H), 4.94–4.91 (m, 1H), 4.41 (d, J = 4.8 Hz, 2H). 13C-NMR
((CD3)2SO): d 150.2, 146.8, 129.8, 115.5, 114.4, 113.7, 58.7. HRMS (FAB) calcd
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Y. Li et al.
Table 1 Synthesis of 4 from 3
O
O
O
R'
Cl
R'
R'
O
R'
O
O
O
O
RO
O
RO
OH
OR
OR
Et3N or DMAP
THF, r.t.
O
3
O
4
Entry
Substrate 3
Acid chloride/Base
Product 4
Yielda
O
O
O
O
O
1
2
3
4
5
6
7
3a
81%
Cl
/ Et3N
n-Bu-O
O
O-n-Bu
O-n-Bu
O-n-Bu
OEt
O
4a
4b
4c
O
O
O
O
O
3a
3a
3b
3b
3b
3c
79%
75%
79%
70%
80%
76%
Cl
/ Et3N
n-Bu-O
n-Bu-O
EtO
O
O
O
O
O
O
O
Cl
/ Et3N
O
O
O
O
O
O
O
Cl
/ DMAP
O
O
4d
O
O
O
O
O
Cl
/ DMAP
EtO
O
OEt
O
4e
O
O
Ph
OEt
O
O
Cl
Cl
Ph
Ph
/ DMAP
EtO
O
O
O
4f
O
O
Ph
OMe
O
O
O
/ DMAP
MeO
O
O
4g
a
Isolated yield
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Synthesis of 2,5-(4-alkoxybenzoyloxy)benzyl acrylates…
69
for C7H8O3 (MH?): 140.0473; found: 140.0476. Elemental analysis: calc 59.99 %
C, 5.75 % H; found 59.88 % C and 5.65 % H.
Synthesis of 6
2-(hydroxymethyl)benzene-1,4-diol (5) (100 mg, 0.71 mmol) was dissolved in
10 mL CH3CN. To the solution, pyridinium p-toluenesulphonate (178 mg,
0.71 mmol) was added. To the mixture a solution of 3,4-dihydro-2H-pyran
(60 mg, 0.71 mmol) in 10 mL CH3CN was added. The mixture was stirred at r.t.
for 48 h. After removal of the solvent under vacuum, the residue was purified by
column chromatography (SiO2, PE/EtOAc = 1:1) to afford compound 6 (80 mg,
yield: 50 %). IR (neat): 3306, 3035, 2870, 1613, 1455 cm-1. 1H-NMR ((CD3)2SO):
d 8.71 (s, 1H), 8.65 (s, 1H), 6.70 (d, J = 2.8 Hz, 1H), 6.60–6.55 (m, 1H), 6.49–6.46
(m, 1H), 4.67–4.66 (m, 1H), 4.56 (d, J = 12.4 Hz, 1H), 4.36 (d, J = 12.4 Hz, 1H),
3.83–3.77 (m, 1H), 3.49–3.45 (m, 1H), 1.76–1.72 (m, 1H), 1.68–1.62 (m, 1H),
1.53–1.47 (m, 4H). 13C-NMR ((CD3)2SO): d 150.1, 147.4, 125.7, 115.9, 115.3,
114.7, 97.8, 63.8, 61.6, 30.7, 25.5, 19.5. HRMS (FAB) calcd for C12H16O4 (MH?):
224.1049; found: 224.1051. Elemental analysis: calc 64.27 % C, 7.19 % H; found
64.20 % C and 7.10 % H.
Synthesis of 7a (method A)
To a mixture of 4-butoxybenzoic acid (110 mg, 0.57 mmol) and DCC (120 mg,
0.58 mmol) in 3 mL CH2Cl2 was added a solution of 6 (40 mg, 0.18 mmol) and
DMAP (70 mg, 0.57 mmol) in 3 mL CH2Cl2. The mixture was stirred at r.t. for
12 h. After removal of the solvent under vacuum, the residue was purified by
column chromatography (SiO2, PE/EtOAc = 5:1) to afford compound 7a (51 mg,
yield: 46 %).IR (neat): 2640, 2360, 1728, 1720, 1660, 1644, 1468, 1392, 1164,
1
1072 cm-1. H-NMR (CDCl3): d 8.18–8.16 (m, 4H), 7.42 (d, J = 2.4 Hz, 1H),
7.28–7.20 (m, 2H), 7.01–6.99 (m, 4H), 4.80 (d, J = 12.8 Hz, 1H), 4.68 (t,
J = 3.2 Hz, 1H), 4.55 (d, J = 12.8 Hz, 1H), 4.08 (t, J = 6.4 Hz, 4H), 3.85–3.79
(m, 1H), 3.50–3.45 (m, 1H), 1.87–1.80 (m, 5H), 1.68–1.43 (m, 9H), 1.02 (t,
J = 7.6 Hz, 6H). 13C-NMR (CDCl3): d 164.8, 164.5, 163.6, 163.5, 148.6, 146.1,
132.3, 132.3, 132.2, 123.3, 122.2, 121.6, 121.2, 114.3, 114.3, 97.9, 68.0, 63.7, 61.8,
31.1, 30.3, 25.4, 19.2, 19.1, 13.8. HRMS (FAB) calcd for C34H40O8 (MH?):
576.2723; found: 576.2720. Elemental analysis: calc 70.81 % C, 6.99 % H; found
70.64 % C and 6.87 % H.
Synthesis of 7b (method B)
To a mixture of 6 (151 mg, 0.67 mmol) and DMAP (246 mg, 2.01 mmol) in 15 mL
CH2Cl2 DIC (255 mg, 2.02 mmol) was added. The mixture was stirred for 10 min.
To the mixture, a solution of 4-ethoxybenzoic acid (336 mg, 2.02 mmol) in 15 mL
CH2Cl2 was added. The mixture was stirred at r.t. for 12 h. After removal of the
solvent under vacuum, the residue was purified by column chromatography (SiO2,
PE/EtOAc = 5:1) to afford compound 7b (153 mg, yield: 41 %). IR (neat): 2640,
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Y. Li et al.
2360, 1728, 1720, 1660, 1644, 1468, 1392, 1316, 1164, 1072, 1036 cm-1. 1H-NMR
(CDCl3): d 8.16–8.13 (m, 4H), 7.39 (d, J = 2.4 Hz, 1H), 7.24–7.17 (m, 2H),
6.98–6.96 (m, 4H), 4.77 (d, J = 12.8 Hz, 1H), 4.66 (t, J = 3.2 Hz, 1H), 4.52 (d,
J = 12.8 Hz, 1H), 4.13 (q, J = 6.8 Hz, 4H), 3.82–3.76 (m, 1H), 3.47–3.42 (m, 1H),
1.88–1.73 (m, 2H), 1.69–1.53 (m, 2H), 1.48–1.45 (m, 8H). 13C-NMR (CDCl3): d
168.3, 167.0, 164.8, 163.4, 148.6, 146.1, 132.3, 132.3, 132.2, 123.3, 122.2, 121.6,
121.5, 121.3, 114.3, 114.3, 97.9, 63.8, 63.7, 61.8, 30.3, 25.4, 19.1, 14.7. HRMS
(FAB) calcd for C30H32O8 (MH?): 520.2097; found: 520.2091. Elemental analysis:
calc 69.22 % C, 6.20 % H; found 69.14 % C and 6.13 % H.
Synthesis of 7c (method B)
To a mixture of 6 (150 mg, 0.67 mmol) and DMAP (246 mg, 2.01 mmol) in 15 mL
CH2Cl2 DIC (255 mg, 2.02 mmol) was added. The mixture was stirred for 10 min.
To the mixture, a solution of 4-methoxybenzoic acid (305 mg, 2.00 mmol) in
15 mL CH2Cl2 was added. The mixture was stirred at r.t. for 12 h. After removal of
the solvent under vacuum, the residue was purified by column chromatography
(SiO2, PE/EtOAc = 5:1) to afford compound 7c (152 mg, yield: 43 %). IR (neat):
2640, 2360, 1728, 1720, 1660, 1644, 1468, 1392, 1164, 1064, 1036 cm-1. 1H-NMR
(CDCl3): d 8.20–8.18 (m, 4H), 7.43–7.42 (m, 1H), 7.27–7.21 (m, 2H), 7.03–7.00
(m, 4H), 4.80 (d, J = 12.8 Hz, 1H), 4.68 (s, 1H), 4.54 (d, J = 12.8 Hz, 1H), 3.92 (s,
6H), 3.85–3.79 (m, 1H), 3.49–3.46 (m, 1H), 1.83–1.76 (m, 1H), 1.74–1.56 (m, 5H).
13C-NMR (CDCl3): d 164.8, 164.5, 164.0, 163.9, 148.6, 146.1, 132.3, 132.3, 132.2,
123.3, 122.2, 121.7, 113.9, 113.8, 97.9, 63.7, 61.8, 55.5, 30.3, 25.4, 19.1. HRMS
(FAB) calcd for C28H28O8 (MH?): 492.1784; found: 492.1791. Elemental analysis:
calc 68.28 % C, 5.73 % H; found 68.20 % C and 5.68 % H.
General procedure for the synthesis of 3
To a solution of 7 in MeOH, excess CuSO4.5H2O was added. The mixture was
stirred at r.t. for 48 h. The solvent was removed under vacuum. The residue was
diluted with water and extracted by EtOAc. The combined organic layer was dried
over Na2SO4. After filtration, the filtrate was concentrated under vacuum, and the
residue was purified by column chromatography (SiO2, PE/EtOAc = 2:1) to afford
3 in 52–57 % yield.
General procedure for the synthesis of 4
Compound 3 and base (Et3N or DMAP) were dissolved in THF. To the mixture, a
solution of appropriate acid chloride in THF was added dropwise at 0 °C. After
stirred at 0 °C for 4 h, the mixture was diluted with water and extracted by EtOAc.
The combined organic layer was dried over Na2SO4. After filtration, the filtrate was
concentrated under vacuum, and the residue was purified by column chromatog-
raphy (SiO2, PE/EtOAc = 2:1) to afford 4 in 70–81 % yield.
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71
Acknowledgments This work is supported by the National Science Foundation of China (NSFC
21302011) and the Fundamental Research Funds for the Central Universities (2016JBM069).
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