Synthesis of methylene butyrolactone polymers from itaconic acid

Article abstract of DOI:10.1002/pola.28654

Herein, we report the transformation of β-monomethyl itaconate, an inexpensive and biorenewable alternative to petroleum feedstocks, to the high-value monomer α-methylene-γ,γ-dimethyl-γ-butyrolactone (Me₂MBL) through a selective addition strategy. This strategy is also applied to the synthesis of α-methylene-γ-butyrolactone (MBL, tulipalin A), a monomer that can be polymerized to give materials with desirable properties (high decomposition temperature, glass transition temperature, and refractive index). Subsequent polymerization of both Me₂MBL and MBL through reversible addition-fragmentation chain-transfer polymerization generates well-defined poly(Me₂MBL) and poly(MBL) (PMBL). Physical characterization of poly(Me₂MBL) shows good physical properties comparable with known PMBL materials.

Full text of DOI:10.1002/pola.28654

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Synthesis of Methylene Butyrolactone Polymers from Itaconic Acid
1
1
1
1
Jacob T. Trotta, Mengyuan Jin, Katherine J. Stawiasz, Quentin Michaudel,
2
1
Wei-Liang Chen, Brett P. Fors
1
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853
Department of Materials Science and Engineering, Cornell University, Ithaca, New York 14853
2
Correspondence to: B. P. Fors (E-mail: bpf46@cornell.edu)
Received 19 April 2017; accepted 3 May 2017; published online 00 Month 2017
DOI: 10.1002/pola.28654
ABSTRACT: Herein, we report the transformation of b-
monomethyl itaconate, an inexpensive and biorenewable alter-
native to petroleum feedstocks, to the high-value monomer a-
addition-fragmentation chain-transfer polymerization generates
well-defined poly(Me MBL) and poly(MBL) (PMBL). Physical
characterization of poly(Me MBL) shows good physical proper-
ties comparable with known PMBL materials. VC
2
2
2
methylene-c,c-dimethyl-c-butyrolactone (Me MBL) through a
2017 Wiley
selective addition strategy. This strategy is also applied to the
synthesis of a-methylene-c-butyrolactone (MBL, tulipalin A), a
monomer that can be polymerized to give materials with desir-
able properties (high decomposition temperature, glass transi-
tion temperature, and refractive index). Subsequent
Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 00,
000–000
KEYWORDS: biorenewable; controlled radical polymerization;
itaconic acid; radical polymerization; reversible addition-
fragmentation chain-transfer (RAFT); renewable resources
2
polymerization of both Me MBL and MBL through reversible
INTRODUCTION In recent years, the development of biore-
petroleum-based poly(acrylic acid) for applications such as
super-absorbents and dispersants.
5
newable resources in the chemical industries has become a
1
major research area. The discovery of sustainable solutions
While the industrial development of PIA clearly establishes it
from non-petroleum chemical feedstocks is a critical need as
we look beyond the currently used nonrenewable resources.
For this reason, the advancement of high-value polymers
from “green” monomers is a challenge that must be met.
This need to “go green” is coupled with the necessity of
developing sustainable polymers in a way that is also eco-
nomically competitive with their petroleum-based equiva-
lents. To accomplish this, the production of high-value
monomers from inexpensive, biosourced small molecule
feedstocks is necessary.
as an important polymer, its synthesis is currently limited to
6–17
uncontrolled radical polymerization.
Importantly, the
polymerization of IA and its derivatives (such as the various
mono- and diesters) in controlled radical polymerization
(
CRP) processes would allow these monomers to be incorpo-
rated into polymers with precisely controlled architectures,
which would greatly increase the number of applications
these materials could be used in. Unfortunately, itaconates
1
8–22
are not amenable to CRP processes.
On this basis, we
sought a simple and efficient transformation that would con-
vert IA into a monomer that could be used in CRP.
Itaconic acid (IA, Fig. 1) is a biorenewable feedstock that
holds considerable promise in reducing society’s dependence
on petroleum-based chemicals. Named in 2004 by the U.S.
Department of Energy as one of the “top value added chemi-
cals from biomass,” IA is currently produced globally on an
In our search for chemical transformations of IA that would
afford monomers compatible with CRP methods, we noticed
its structural similarity to a-methylene-c-butyrolactone (MBL,
Fig. 1). MBL has been shown to be compatible with a wide
8
0 kiloton/year scale for ꢀ$2/kg from the fermentation of
variety of controlled polymerization strategies such as atom-
2
–4
23–42
biomass such as corn or rice.
Recognizing the potential of
transfer radical-polymerization.
Additionally, poly(MBL)
this feedstock chemical for industrial use, the company Itaco-
nix has developed a robust uncontrolled radical polymeriza-
tion process that provides poly(itaconic acid) (PIA) for ꢀ$3/
(PMBL) has been established as a suitable surrogate for
petroleum-derived poly(methyl methacrylate) (PMMA), due
4
3–45
to its similar structure and optical properties.
Interest-
5
kg. PIA has been shown to be an excellent surrogate for
ingly, the thermal properties of PMMA and PMBL differ
Additional Supporting Information may be found in the online version of this article.
2017 Wiley Periodicals, Inc.
V
C
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While these methods set the foundation for the construction of
MBL derivatives from IA, we wished to improve upon their effi-
cacy by reducing the number of steps required and by adding
new functionality into the lactone backbone not previously
accessed from IA.
Herein, we report a new strategy for the synthesis of a-
methylene-c,c-dimethyl-c-butyrolactone [Me MBL, Fig. 2(e)]
2
in a single step from commercially available 2 through selec-
tive Grignard addition. Additionally, a similar reduction strat-
egy was used to produce MBL from 2 in a single step in
42% yield. Subsequent reversible addition-fragmentation
chain-transfer (RAFT) polymerization of both MBL and
Me MBL was performed.
2
EXPERIMENTAL
FIGURE 1 Our strategy to convert itaconic acid, produced by
the fermentation of biomass such as corn or rice, into high-
value PMMA surrogates through the transformation to, and
controlled polymerization of, methylenebutyrolactones. [Color
figure can be viewed at wileyonlinelibrary.com]
General Reagent Information
b-MMI (2, 98%, TCI), ethyl acetate (99.5%, Fisher), hexanes
(
(
98.5%, Fisher), methanol (MeOH, 99.8%, Fisher), benzene
99.0%, EMD Millipore), chloroform (99.8%, J.T. Baker),
dimethyl sulfoxide (99.9%, Fisher), acetic acid (glacial, EMD
Millipore), chloroform-D (99.8%, Cambridge Isotope Labora-
greatly, with PMBL possessing a glass transition temperature
(
T ) approximately 100 8C higher than that of PMMA (ꢀ200 8C
g
43,44
tories, Inc.), dimethyl sulfoxide-D6 (DMSO-d , 99.9%, Cam-
6
for PMBL and ꢀ100 8C for PMMA).
g
This increased T ena-
bridge Isotope Laboratories, Inc.), anhydrous magnesium
sulfate (98.0%, EMD Millipore), anhydrous sodium sulfate
bles the use of PMBL and related polymers for high tempera-
4
6
ture applications for which PMMA would be unsuitable.
(
99.0%, BDH), methyl magnesium chloride (MeMgCl, 3.0 M
Therefore, the efficient production of MBL and related deriva-
tives from IA lends itself toward numerous applications.
in THF, Sigma-Aldrich), methyl methacrylate (99%, Aldrich),
sodium borohydride (NaBH , 98%, Acros), lithium borohy-
4
MBL is a naturally occurring compound found in tulips; how-
dride (LiBH4, 95%, Strem), sodium cyanoborohydride
4
7
ever, its large scale production is not practical. This limited
availability of MBL hampers the potential use of PMBL as a
PMMA surrogate. Additionally, while the synthesis of MBL and
related derivatives from inexpensive starting materials has
been extensively studied since the 1960s, these syntheses gen-
erally require several steps and often rely on petroleum-based
(NaCNBH , 95%, Sigma-Aldrich), lithium aluminum hydride
3
(LiAlH , 1.0 M in THF, Aldrich), lithium triethylborohydride
4
V
R
(
Super-Hydride , LiEt BH, 1.0M in THF, Aldrich)
3
4
8–50
acrylates as starting materials.
Thus, the use of IA as a
feedstock chemical to produce MBL and related compounds
represents a grand challenge in green monomer synthesis.
A few methods for the production of MBLs from IA derivatives
have been demonstrated in the past. Notably, Fetizon et al.
showed in 1975 that dimethyl itaconate can be reduced to diol
1
with Red-Al, followed by oxidative cyclization with Ag CO
2 3
5
1
on celite to yield MBL in 80% yield from 1 [Fig. 2(a)]. Anions
of IA derivatives have also been added to aldehydes and
ketones, followed by lactonization, to generate carboxylic acid
functionalized MBLs. Additionally, a patent by Yokota and
Hirabayashi in 1992 claims that selective reduction of b-
monomethyl itaconate (b-MMI) (2), followed by acid-catalyzed
5
2
5
3
cyclization, could produce MBL in 49% yield [Fig. 2(b)]. Ally-
lation of commercially available itaconic anhydride, 3, with
allyltrimethylsilane and stoichiometric TiCl was reported in
4
5
4
2
000 by Santelli and Parrain to generate 4 [Fig. 2(c)]. More
recently, b-MeMBL, a well-studied MBL derivative, was synthe-
sized on large scale in six steps from IA by Chen in 2014 [Fig.
FIGURE 2 (a–d) Previous work on the synthesis of MBL analo-
gies from IA derivatives; (e) this work. [Color figure can be
viewed at wileyonlinelibrary.com]
2
(d)], demonstrating the potential of this chemical feedstock
5
5
for industrially relevant transformations to green monomers.
2
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diisobutylaluminum hydride (DIBAL-H, 1.0M in hexanes,
Aldrich)VR, sodium bis(2-methoxyethoxy)aluminumhydride
software. Refractive indices and Abbe numbers were deter-
mined by ellipsometry using
Ellipsometer.
a Woollam Spectroscopic
(
Red-Al , 60 wt% in toluene, Aldrich), sodium triacetoxybor-
ohydride (Na(OAc) BH, 95%, Aldrich) and 2-cyano-2-propyl
benzodithioate (97%, Sigma-Aldrich) were used as received.
Water was obtained by reverse osmosis. Tetrahydrofuran
3
Preparation of Polymer Thin Films for Optical Property
Measurements
Thin films of PMBL and PMe
coating a 60-mg/mL polymer solution of PMBL in dimethyl
sulfoxide or PMe MBL in chloroform onto a silicon wafer.
2
MBL were prepared by spin
(
THF, 99%, Macron) was purified by passing through two
neutral alumina columns on the JC Meyer solvent system.
HCl (Macron) was used as received and diluted with water
to make a 3 M solution. Azobisisobutyronitrile (AIBN, Sigma,
2
The silicon wafers were cut, cleaned with a piranha solution,
rinsed with water, dried, and cleaned with plasma before
spin coating.
98.0%) was recrystallized from MeOH before use. Piranha
solution was prepared by mixing sulfuric acid (95–98%,
BDH) and hydrogen peroxide (30%, Fisher) in a 3:1 (v/v)
Synthesis of Me MBL
2
ratio. Anhydrous cerium (III) chloride (CeCl
3
) was prepared
2
(30. g, 0.21 mol, 1.0 equiv) was weighed out and trans-
from cerium(III) chloride heptahydrate (99.9%, Sigma-
ferred to a dry 1 L round-bottom flask equipped with a stir
bar and capped with a rubber septum. The flask was then
evacuated and backfilled with nitrogen. THF (0.14 L, 1.5 M
of 2 in THF) was added by syringe and the solution was
cooled to 0 8C. Methyl magnesium chloride (0.22 L, 3.0 M,
5
6
Aldrich) following a known procedure. Silicon wafers for
spin coating were purchased from Purewafer, a WRS material
company (item. no. 4N0SSP-004). Silica used for column
chromatography was purchased from SiliCycle (SiliaFlash
Irregular Silica Gels, P60, 40–63 mm, 60Å).
0.65 mol, 3.1 equiv) was then added slowly over 15 minutes
by syringe. The reaction was stirred at 0 8C for 2 h and then
quenched by slow addition of HCl (0.33 L, 3 M, 0.99 mol, 4.7
equiv) to give a biphasic mixture with a pH of 0 in the aque-
ous phase. The biphasic mixture was then warmed to room
temperature and stirred vigorously for 3 h. The reaction mix-
ture was extracted three times with ethyl acetate and the
organic layers were combined, dried with anhydrous magne-
sium sulfate, filtered, and concentrated under reduced pres-
sure in a rotary evaporator to give dark brown oil. Fractional
distillation of the crude oil at 85 8C under a 50-mTorr vac-
uum gave a 35 8C vapor that condensed to give a clear, color-
less liquid with a measured density of 1.0 g/mL in 39%
isolated yield (10.3 g, 0.082 mol).
General Analytical Information
All PMe MBL samples were analyzed using a Tosoh EcoSec
2
HLC 8320GPC system with two SuperHM-M columns in
series at a flow rate of 0.350 mL/min at 40 8C. THF was
used as the eluent and all number-average molecular
weights (M ), weight-average molecular weights (M ), and
n
w
dispersities (Ð) for PMe MBL were determined by light scat-
2
tering using a Wyatt miniDawn Treos multi-angle light scat-
tering detector. The dn/dc value for PMe MBL in THF was
calculated from light scattering to be 0.0853 mL/g . All
2
2
PMBL polymer samples were analyzed using a GPC system
composing of a Waters 515 pump and three PSS GRAM col-
umns (100–1000–3000) in series at a flow rate of 1.0 mL/
min at 25 8C. DMF was used as the eluent and all M s, M s,
and Ðs for PMBL were determined from refractive index
chromatograms against Fluka polystyrene standards using an
Agilent 1200 refractive index detector. Nuclear magnetic res-
onance spectra were recorded on a Mercury 300 MHz, a Var-
ian 400 MHz, a Bruker 500 MHz, or a Varian 600 MHz
instrument. Mass spectra were performed on an Exactive
Plus Orbitrap Mass Spectrometer with a DART SVP ion
source from Ion Sense. IR spectra were recorded on a
Thermo Scientific Smart Orbit Nicolet Avatar 370 DTGS FTIR
1
n
w
H NMR (500 MHz, CDCl , d, ppm): 6.19 (t, J 5 2.5 Hz, 1H),
.59 (t, J 5 2.4 Hz, 1H;), 2.73 (s, 2H), 1.41 (s, 6H); C NMR
3
13
5
(
2
1
125 MHz, CDCl , d, ppm): 169.9, 136.2, 122.2, 81.7, 41.3,
3
8.5; IR (ATR, cm ): m 5 2972, 1749, 1663, 1373, 1262,
21
186, 1094, 1080, 935, 929, 813, 749, 619; HRMS (DART-
1
MS, m/z): [MH] calcd for C H O , 127.076; [MH]1 found,
7
11 2
127.076.
Synthesis of a-Methylene-c-butyrolactone (MBL)
A 2-dram glass vial equipped with a stir bar was charged
with 2 (29 mg, 0.21 mmol, 1.0 equiv) and sodium borohy-
dride (46 mg, 1.2 mmol, 5.7 equiv). The vial was capped
with a septum and evacuated and backfilled with nitrogen.
THF (1.6 mL, 0.13 M of 2 in THF) was then added via
syringe at 0 8C and the mixture was stirred for 5 min. Water
(0.4 mL, 22.2 mmol, 106 equiv) was then added dropwise at
0 8C, and after another 5 min, the reaction mixture was place
in an oil bath pre-heated to 32 8C and was stirred for 6.5 h.
The reaction was cooled to room temperature and quenched
with HCl (3 M) and diluted with ethyl acetate. The mixture
was then extracted three times with ethyl acetate and the
organic layers were combined, dried with anhydrous magne-
sium sulfate, filtered, and concentrated under reduced pres-
sure in a rotary evaporator. Purification by chromatography
equipped with
a
diamond ATR attachment (30,000–
2
1
200 cm ). Differential scanning calorimetry (DSC) measure-
ments of polymer samples were performed on a Mettler-
Toledo Polymer DSC instrument equipped with a chiller and
an autosampler. Samples were prepared in aluminum pans
and were analyzed using the following heating program:
2
70 8C to 240 8C at 10 8C/min, 240 8C to 270 8C at 10 8C/
min, and then 270 8C to 240 8C at 10 8C/min. Data were
processed using StarE software. All reported T s were
observed on the second heating cycle. Thermogravimetric
analysis (TGA) was performed on a TA Instruments Q500
Thermogravimetric Analyzer. Samples were heated under
nitrogen atmosphere at a rate of 20 8C/min from 25 8C to
g
600 8C. Data were processed using Universal Analysis
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(
SiO , 50% ethyl acetate, 49% hexanes, 1% acetic acid) gave
2
TABLE 1 Optimization of the Reduction of b-MMI to Me MBL
2
the pure alcohol, c-hydroxy-a-methylenebutyric acid (56%).
[Color table can be viewed at wileyonlinelibrary.com]
1
H NMR (500 MHz, CDCl , d, ppm): 6.70 (br s, 1H), 6.37 (s,
H), 5.77 (s, 1H), 3.79 (t, 2H), 2.58 (t, 2H); C NMR (125
3
1
3
1
MHz, CDCl , d): 172.0, 137.0, 129.7, 61.7, 35.2; IR (ATR,
3
2
1
cm ): m 5 3590–2350, 1690, 1620, 1410, 1280, 1200, 1150,
030, 946, 864, 823, 773, 679; HRMS (DART-MS, m/z):
a
b
Entry
Solvent
Methyl Source (Equiv)
% Yield
1
1
[
MH] calcd for C H O , 117.055; found, 117.055.
1
2
3
4
5
6
7
8
THF
THF
DCM
DCM
THF
THF
THF
THF
THF
MeLi (5.1)
8
5
9 3
MeMgCl (3.1)
49
51
55
43
31
15
23
Cyclization of 7 was performed in a separate step or as part of
an acid workup after reduction of 2. As a separate step: after
concentration of the organic layers following extraction,
MeMgCl (3.1), 1 M in DCM
MeMgCl (4.1), 1 M in DCM
c
1.0 mL of THF and 1.0 mL of 3 M HCl were added to the crude
MeMgCl (3.1)
d
oil. The mixture was then stirred overnight for 9 h and
extracted three times with ethyl acetate. The combined organic
layers were dried with magnesium sulfate, filtered, and con-
centrated on the rotary evaporator to give MBL in 93% yield
from the alcohol (52% yield from 2). As part of the acid
workup: After 6.5 h at 32 8C, 2.0 mL of 3 M HCl was added to
the reaction mixture and was allowed to stir overnight for
MeMgCl (3.1)
3
CeCl /MeLi (4.1)
3
CeCl /MeMgCl (4.1)
e
f
9
MeMgCl (3.1)
39
a
Reactions conditions: 1.0 mmol scale at 1 M.
Yields were determined by H NMR using an internal standard.
Slow addition of Grignard reagent.
b
c
d
e
f
1
13 h. The mixture was then extracted with ethyl acetate five
Slow addition of 2.
times, dried with sodium sulfate, filtered, and concentrated on
the rotary evaporator to give the crude lactone product, MBL,
in 45% overall yield from 2. Purification by chromatography
Reaction was performed on a 0.21 mol scale (30 g of 2) at 1.5 M.
Isolated yield.
(
SiO , 30% ethyl acetate, 69% hexanes, 1% acetic acid) gave
vial by syringe. The combined reagents were mixed to homo-
geneity and then degassed by three freeze–pump–thaw
cycles. The degassed solution was kept under vacuum and
submerged in an oil bath preheated to 80 8C. The reactions
were stirred for 35 min. After the reaction mixture had
gelled, it was removed from the heat and dissolved in DMF.
2
pure MBL in 42% isolated yield from 2. Characterization data
matched those reported in the literature.
1
H NMR (400 MHz, CDCl , d, ppm): 6.26 (t, J 5 3.0 Hz, 1H),
3
5
.67 (s, J 5 2.6 Hz, 1H), 4.37 (t, J 5 7.2 Hz, 2H), 2.98 (m, 2H).
1
Aliquots were then taken for H NMR analysis in DMSO-d6
RAFT Polymerization of Me MBL
Me MBL (0.2 mL, 0.2 g, 1.6 mmol, 1100 equiv) was added
2
to obtain conversion and SEC analysis to obtain M , M , and
n
w
2
Ð. The viscous solution was then precipitated in cold
230 8C) MeOH and the solid polymer was isolated by filtra-
tion. The light pink powder was then dried overnight at
00 8C in a vacuum oven before thermal analysis.
by syringe to a 2-dram vial equipped with a stir bar and a
cap with a Teflon septum. Following this, AIBN (0.05 mL, 4.6
mg/mL in benzene, 0.23 mg, 0.0014 mmol, 1.0 equiv) and 2-
cyano-2-propyl benzodithioate (0.05 mL, 31 mg/mL in ben-
zene, 1.6 mg, 0.0070 mmol, 5.0 equiv) were added to the
vial by syringe. The combined reagents were mixed to homo-
geneity and then degassed by three freeze–pump–thaw
cycles. The degassed solution was kept under vacuum and
submerged in an oil bath pre-heated to 80 8C. The reaction
was stirred for 15 h. After the reaction mixture had gelled, it
was removed from the heat and dissolved in THF. Aliquots
were then taken for H NMR analysis in CDCl
version and SEC analysis to obtain M , M , and Ð. The vis-
cous solution was then precipitated in cold (230 8C)
hexanes and the solid polymer was isolated by filtration. The
light pink powder was then dried overnight at 100 8C in a
vacuum oven before thermal analysis.
(
1
RESULTS AND DISCUSSION
Synthesis of Me MBL
2
We postulated that selective addition of a methyl anion to b-
MMI (2), followed by acid catalyzed cyclization would yield
Me
MBL. To test this, we added methyl lithium (MeLi) to 2 in
MBL was formed in a
2
THF at 0 8C. After an acid workup, Me
2
1
to obtain con-
modest 8% yield (Table 1, entry 1). Interestingly, the replace-
ment of MeLi with MeMgCl resulted in an increase in yield to
49% (Table 1, entry 2). Switching the solvent from THF to
DCM resulted in a similar yield of 51% with 3.1 equiv of
MeMgCl and 55% with 4.1 equiv of MeMgCl (Table 1, entries 3
and 4). Slow addition of the MeMgCl to a solution of 2, or of a
solution of 2 to MeMgCl, both led to reduced yields of 43%
and 31% yield, respectively (Table 1, entries 5 and 6).
3
n
w
RAFT Polymerization of MBL
MBL (0.14 mL, 0.16 g, 1.6 mmol, 1100 equiv) was added by
syringe to a 2-dram vial equipped with a stir bar and a cap
with a Teflon septum. Following this, AIBN (0.05 mL, 4.6
mg/mL in benzene, 0.23 mg, 0.0014 mmol, 1.0 equiv) and 2-
cyano-2-propyl benzodithioate (0.05 mL, 31 mg/mL in ben-
zene, 1.6 mg, 0.0070 mmol, 5.0 equiv) were added to the
Based on the NMR spectrum of the reaction mixtures, we
hypothesized that some of the mass balance consisted of a
complex mixture of aliphatic products. To increase selectivity
toward 1,2-addition and to avoid any potential enolate based
reaction pathways, we sought to change our methyl anion
4
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TABLE 2 Optimization of the Reduction of b-MMI to MBL [Color table can be viewed at wileyonlinelibrary.com]
a
b
c
Entry
Solvent
T ( 8C)
t (h)
Red.
% Yield
1
2
3
4
5
6
7
8
9
MeOH:THF (3:2)
THF
RT
278
278
278
278
60
144
7
NaBH
DIBAL-H (3)
LiAlH (3)
4
(6)
0
Trace
0
THF
2
4
V
R
THF
0.5
2
Red-Al (4)
LiEt BH (4)
NaBH (6)
Na(OAc) H (10)
NaCNBH (3)
0
THF
3
Trace
Trace
0
MeOH:THF (3:2)
MeOH:THF (3:2)
2
4
60
96
24
1
3
H
2
H
2
H
2
H
2
H
2
H
2
O:THF (1:4)
O:THF (1:19)
O:THF (2:3)
O:THF (1:4)
O:THF (1:4)
O:THF (1:4)
60
3
0
40
NaBH
NaBH
NaBH
4
4
4
(6)
(6)
(6)
25
10
11
12
13
40
4
41
32
6.5
5
56
60
LiBH
4
(6)
11
d
e
32
6.5
NaBH
4
(6)
45 (42 )
a
b
c
d
e
Solvent (v:v).
NMR yield of MBL.
Reducing agent (equiv).
Isolated yield of MBL.
1
Yield of 7 determined by H NMR against an internal standard before
acid workup.
source. Using chemistry developed by Imamoto in the 1980s,
we used organocerium reagents, which have shown excellent
Based on the above results, we tested NaCNBH , a milder
3
reducing agent compared to NaBH . Using this reagent at
4
60 8C (Table 2, entry 8) in a mixture of THF and water, no
reaction occurred and only unreacted starting material was
collected. Despite this outcome, we decided to apply the
5
6–58
selectivity for 1,2-addition.
Unfortunately, addition of
CeCl to reactions using both MeLi and MeMgCl did not lead
3
to improved yields (Table 1, entries 7 and 8).
aqueous conditions used for the NaCNBH
3
reduction to
Using the conditions in entry 2 (Table 1), the reaction was
NaBH . Interestingly, 25% yield of the desired alcohol prod-
4
scaled up and performed on 30 g of 2, generating Me MBL
2
uct was observed after 1 h at 40 8C (Table 2, entry 9). Opti-
mization of the THF to water ratio and the reaction
temperature led to the selective reduction of 2 to give alco-
hol 7 in 56% yield (Table 2, entries 10 and 11). Substitution of
NaBH with LiBH using these aqueous conditions (Table 2,
in 39% isolated yield after distillation (Table 1, entry 9).
This result clearly demonstrates that this is a practical
method for the synthesis of Me MBL.
2
4
4
Reduction of 2 to MBL
entry 12) resulted in a lowered yield of 11%. Using the opti-
mized conditions performed in entry 11, treatment of the final
product with acid upon workup enabled the one-pot formation
of MBL in 45% overall yield (Table 2, entry 13). The positive
effect of the aqueous media on yield, as well as the relative
ratio of water to THF, deserves discussion. For NaBH , aqueous
conditions can lead to the formation of NaB(OH)H , a known
intermediate in the stepwise hydrolysis of NaBH
hydroxyborohydride has been reported to reduce esters.
Encouraged by our results on the synthesis of Me MBL, we
2
wanted to investigate the reduction of 2 to give the parent
MBL. Yokota and Hirabayashi patented a procedure that
allowed this transformation using LiBH ; however, we did
4
not observe any desired product when we attempted the
5
3
4
reported conditions. Therefore, we probed other reducing
3
agents and conditions for this reaction. Subjecting 2 to
59–63
4
.
This
NaBH in THF/MeOH resulted in no desired product (Table
63–65
4
2, entry 1). Switching to a stronger reducing agent, DIBAL-H,
The varying ratios of water likely affect the rate of formation
produced mainly undesired diol 1, with a trace of desired
and stability of NaB(OH)H . Additionally, itaconic acid forms
3
5
1
product 7
,
observed by NMR (Table 2, entry 2). Compara-
as a side-product under these reaction conditions, so the ratio
of water to THF had to be modified to maximize the formation
of alcohol 7.
V
R
ble results were observed using LiAlH , Red-Al , and LiEt BH
4
3
(
Table 2, entries 3–5). Additional reactions with NaBH4 at
elevated temperatures were also attempted, resulting in
complex mixtures of degradation products with only trace
quantities of 7 (Table 2, entry 6). Similarly, the use of
CRP of Me MBL and MBL
2
To demonstrate Me MBL was a monomer capable of CRPs,
2
6
6
Na(OAc) BH did not produce any 7, resulting instead in only
we investigated its use in RAFT polymerization. To begin,
we used known RAFT conditions used for the polymerization
3
unreacted starting material (Table 2, entry 7).
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TABLE 3 Polymerization Conditions for Me
2
MBL
a
b
c,d
c
d
Entry
M:CTA:I
M
n
Ð
M
n,theo
e
1
1100:5:1
1100:5:1
1100:8:1
1100:6:1
1100:3:1
1100:2:1
1100:1:1
1100:0:1
22.5
17.8
8.8
1.21
1.07
1.25
1.15
1.26
1.25
1.41
2.25
19.2
15.8
8.4
2
3
4
5
6
7
8
11.7
18.7
26.2
61.1
55.7
11.8
21.7
36.8
95.8
54.1
FIGURE 4 Chain extension of PMMA with Me
block copolymer PMMA-b-PMe MBL. [Color figure can be
viewed at wileyonlinelibrary.com]
2
MBL to give the
2
a
To take advantage of the living characteristics of the RAFT
polymerization, we used our optimized conditions to grow
diblock copolymers. To this end, we synthesized a 9.7-kg/
mol PMMA and used it as a macroinitiator for the polymeri-
Reactions were run at 80 8C in a 2:1 monomer:solvent ratio on a 1.6
mmol scale for 10–20 h.
b
Monomer:CTA:initiator ratios.
c
n
M and Ð determined by a light scattering detector coupled with SEC.
Values reported in kg/mol.
d
e
Reaction performed at 60 8C for 60 h.
zation of Me MBL (see Supporting Information for experi-
2
mental conditions), which gave a 22.2-kg/mol Mn PMMA-b-
PMe MBL diblock copolymer with a narrow Ð of 1.11. A
clear shift to higher molecular weight was observed without
2
of MMA with a commercially available chain transfer agent
CTA), 2-cyano-2-propyl benzodithioate (Table 3). Under these
conditions at 60 8C, Me MBL polymerized slowly to give a
(
any major termination (Fig. 4), clearly showing the Me MBL
2
2
can be used to make functional materials.
2
2.5-kg/mol PMe MBL with a D- of 1.21 after 60 h (Table 3,
2
entry 1). Increasing the temperature to 80 8C provided high
conversion within 15 h (Table 3, entry 2) and gave a 17.8-kg/
mol polymer with a narrower D- of 1.07. Modulating the ratio
We next set out to apply our RAFT polymerization conditions
of Me MBL to the controlled polymerization of MBL. Under
2
these conditions, the polymerization of MBL gelled after 35
minutes at 80 8C to give a 14.8-kg/mol polymer with a D- of
of CTA to monomer enabled the synthesis of polymers with
controlled M values ranging from 8.8 to 61.1 kg/mol (Table 3,
n
1
.22 (Table 4, entry 1). Subsequent variation in the MBL:CTA
ratio gave control over Mn while maintaining narrow D-
Table 4, entries 2 and 3, and Supporting Information Fig.
entries 2–7, Fig. 3). Under these conditions, polymerizations
generally gelled after 50% conversion, after which the reaction
was stopped. These results clearly illustrate that this mono-
mer, which is synthesized directly from an IA derivative, can
be efficiently used in CRP processes.
(
S8). Notably, PMe MBL shows improved solubility over
2
PMBL in common organic solvents.
Physical Properties
PMBL and derivatives are known for their high T values rel-
ative to their acyclic PMMA analogues.
Additionally, using only the radical initiator and no CTA,
g
PMe MBL was synthesized in an uncontrolled fashion, giving a
43,44
2
DSC for a 19.7-
5
5.7-kg/mol polymer with a broad of D- of 2.25 (Table 3, entry 8).
kg/mol PMe MBL generated by RAFT polymerization shows
2
g
a T value of 209 8C (Fig. 5). This is comparable both to the
TABLE 4 Polymerization Conditions for MBL
a
b
c,d
c
d
Entry
M:CTA:I
M
n
Ð
M
n,theo
1
2
3
1100:5:1
1100:3:1
1100:7:1
14.8
22.0
12.1
1.22
1.21
1.23
13.9
31.4
10.9
a
Reactions were run at 80 8C in a 2:1 monomer:solvent ratio on a 1.6
mmol scale for 10–20 h.
FIGURE 3 RAFT polymerization of Me
2
MBL leads to predict-
b
Monomer:CTA:initiator ratios.
able M values based on initiator and CTA loading. [Color fig-
n
c
M
n
and Ð determined by SEC against PS standards.
Values reported in kg/mol.
d
ure can be viewed at wileyonlinelibrary.com]
6
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purified by simple distillation. Subsequent controlled poly-
merization of both MBL and Me MBL through RAFT poly-
2
merization generates well-defined polymers with predictable
M s and narrow D- s. Additionally, PMe MBL shows improved
n
2
solubility over PMBL (PMe
2
MBL is soluble in THF while
PMBL is not), making it a potentially more processable poly-
mer. Furthermore, PMe MBL shows a higher T compared
2
g
with PMBL and both polymers show high T s. This new
d
method provides a high-value monomer synthesized from a
commercially available itaconate in a single step that can be
polymerized in a controlled fashion.
2
FIGURE 5 DSC curves of PMe MBL and PMBL. [Color figure
can be viewed at wileyonlinelibrary.com]
5
5.7 kg/mol PMe MBL generated by uncontrolled radical
2
polymerization (204 8C) and the 12.1 kg/mol PMBL gener-
ated by RAFT (187 8C). Additionally, TGA analysis showed a
high decomposition temperature (T ) for PMe MBL gener-
ated by both RAFT (337 8C) and uncontrolled radical poly-
merization (310 8C) (Fig. 6). This result demonstrates that
the dithioester chain end does not lower the stability of the
polymers synthesized using RAFT.
ACKNOWLEDGMENTS
d
2
This work was supported by the NSF through the Center for
Sustainable Polymers (CHE-1413862). This work made use of
the Cornell Center for Materials Research Shared Facilities,
which are supported through the NSF MRSEC program (DMR-
1120296). B.P.F. thanks 3M for a Non-Tenured Faculty Award.
This work made use of the NMR Facility at Cornell University
and is supported, in part, by the NSF under the award number
CHE-1531632.
One of the attractive features of PMBL is its similar optical
properties to PMMA. On this basis, we wanted to measure
4
3
the refractive index and extinction coefficient of PMe MBL to
2
assess its potential use for optical-based applications. Addi-
tionally, as the determination of optical constants such as
refractive index and extinction coefficient are sensitive to the
exact modeling conditions used following the measurement
of raw data, we also measured the optical properties of
PMMA synthesized by RAFT polymerization. A thin film of
PMMA gave a refractive index of 1.57 at 250 nm with an
Abbe number of 53 (Supporting Information Fig. S9), which
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