Rigid Multidimensional Alkoxyamines: A Versatile Building Block Library

Article abstract of DOI:10.1002/ejoc.202001415

Since the discovery of the “living” free-radical polymerization, alkoxyamines were widely used in nitroxide-mediated polymerization (NMP). Most of the known alkoxyamines bear just one functionality with only a few exceptions bearing two or more alkoxyamine units. Herein, we present a library of novel multidimensional alkoxyamines based on commercially available, rigid, aromatic core structures. A versatile approach allows the introduction of different sidechains which have an impact on the steric hindrance and dissociation behavior of the alkoxyamines. The reaction to the alkoxyamines was optimized by implementing a mild and reliable procedure to give all target compounds in high yields. Utilization of biphenyl, p-terphenyl, 1,3,5-triphenylbenzene, tetraphenylethylene, and tetraphenyl-methane results in linear, trigonal, square planar, and tetrahedral shaped alkoxyamines. These building blocks are useful initiators for multifold NMP leading to star-shaped polymers or as a linker for the nitroxide exchange reaction (NER), to obtain dynamic frameworks with a tunable crosslinking degree and self-healing abilities.

Full text of DOI:10.1002/ejoc.202001415

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Rigid Multidimensional Alkoxyamines: A Versatile Building
Block Library
Yannick Matt,[a, b] Isabelle Wessely,[a] Lisa Gramespacher,[a] Manuel Tsotsalas,[c] and
Stefan Bräse*[a, b, d]
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Since the discovery of the “living” free-radical polymerization,
alkoxyamines were widely used in nitroxide-mediated polymer-
ization (NMP). Most of the known alkoxyamines bear just one
functionality with only a few exceptions bearing two or more
alkoxyamine units. Herein, we present a library of novel
multidimensional alkoxyamines based on commercially avail-
able, rigid, aromatic core structures. A versatile approach allows
the introduction of different sidechains which have an impact
on the steric hindrance and dissociation behavior of the
alkoxyamines. The reaction to the alkoxyamines was optimized
by implementing a mild and reliable procedure to give all
target compounds in high yields. Utilization of biphenyl, p-
terphenyl, 1,3,5-triphenylbenzene, tetraphenylethylene, and
tetraphenyl-methane results in linear, trigonal, square planar,
and tetrahedral shaped alkoxyamines. These building blocks are
useful initiators for multifold NMP leading to star-shaped
polymers or as a linker for the nitroxide exchange reaction
(NER), to obtain dynamic frameworks with a tunable cross-
linking degree and self-healing abilities.
Introduction
action with impurities. This suppression is achieved through a
dynamic equilibrium between the reactive radical species and a
non-reactive dormant species. In the case of NMP, alkoxyamines
with their weak CÀ O bond function as dormant species, which
can be activated thermally to give a free nitroxide and the
carbon-centered radical species that can react further. The
transition between active and dormant species accounts for
high control during polymerization. Considering that the
alkoxyamine also serves as an end group after the polymer-
ization, the subsequent addition of a second monomer allows
to achieve defined block-copolymers.[3,5]
Several procedures to synthesize functional alkoxyamines
have been developed over the years. Among others, these
include trapping of C-radicals created with radical starters like
di-tert-butyl peroxide, generation from N-oxoammonium salts,
the addition of radicals to nitrones, and the addition of
nitroxides to alkenes.[6–15] However, the most popular route,
which was used in the herein described work, was developed
by Matyjaszewski et al. and was improved by Nicolas et al. In
their approach, elemental copper was used to generating alkyl
radicals by homolytic cleavage of alkyl halides and subsequent
trapping with a suitable nitroxide.[16,17]
Despite the innumerable procedures and known alkoxy-
amines, very few examples of multifunctional alkoxyamines
have been reported.[18–21] This is remarkable since such multi-
functional alkoxyamines allow the generation of star-shaped
polymers with a defined center and thereby a fixed number of
arms, which find application as viscosity improvers, organic
nanoparticles, and drug delivery systems.[22–25] Alkoxyamines
can also be used as building blocks in the nitroxide exchange
reaction (NER). Nitroxides with (2,2,6,6-tetramethylpiperidin-1-
yl)oxyl (TEMPO) being the most prominent derivative, are stable
free radicals that have unique magnetic and catalytic properties
and serve as a counterpart to the labile alkoxyamines in the
NER.[26–29] During the NER, the alkoxyamine is heated under inert
The nitroxide-mediated polymerization (NMP), as one of the
first “living” free-radical polymerization techniques, was discov-
ered in the early 1980s at the Commonwealth Scientific and
Industrial Research Organization (CSIRO).[1] Since its patenting in
1985, NMP has gained high attention as it exhibits a living
character allowing to generate well-controlled polymers with
low polydispersity at low costs while tolerating functional
groups.[1–5] The crucial step in radical polymerization is the
suppression of an irreversible termination of the propagating
radical, such as a combination of active chain ends, the
abstraction of a hydrogen atom (disproportionation), or inter-
[a] Y. Matt, I. Wessely, L. Gramespacher, Prof. Dr. S. Bräse
Institute of Organic Chemistry – IOC
Karlsruhe Institute of Technology (KIT)
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
E-mail: braese@kit.edu
https://www.ioc.kit.edu/braese
[b] Y. Matt, Prof. Dr. S. Bräse
3DMM2O – Cluster of Excellence (EXC-2082/1-390761711)
Karlsruhe Institute of Technology (KIT)
Kaiserstraße 12, 76131 Karlsruhe, Germany
[c] Dr. M. Tsotsalas
Institute of Functional Interfaces – IFG
Karlsruhe Institute of Technology (KIT)
Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Ger-
many
[d] Prof. Dr. S. Bräse
Institute of Biological and Chemical Systems – IBCS-FMS
Karlsruhe Institute of Technology (KIT)
Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Ger-
many
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202001415
© 2020 The Authors. European Journal of Organic Chemistry published by
Wiley-VCH GmbH. This is an open access article under the terms of the
Creative Commons Attribution Non-Commercial License, which permits use,
distribution and reproduction in any medium, provided the original work is
properly cited and is not used for commercial purposes.
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conditions, to obtain the C-centered radical and a free nitroxide.
by reduction, substitution with HBr, and conversion to the
alkoxyamine with the help of elemental copper and TEMPO.[40]
Herein, we optimized the above-mentioned synthetic route
and describe the synthesis of a library of novel multidimen-
sional alkoxyamines based on rigid, aromatic core structures.
Overall, ten alkoxyamine building blocks with different geo-
metries based on their core have been synthesized (Figure 1).
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Upon addition of a second nitroxide, both nitroxide species
compete for the recombination with the C-radical. Since the
NER is reversible, the thermodynamically favored product is
formed.[30,31] The progress of the NER can be monitored via
electron paramagnetic resonance (EPR) spectroscopy due to the
involved nitroxides with different hyperfine coupling
constants.[32] The NER has been employed for cross-over
reactions, to generate crosslinked polymers as well as self-
assembled microcrystals and to shift reactions out of their Results and Discussion
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equilibrium using light as an activator.[30,33–39] Recently, we were
able to facilitate the NER with multifunctional alkoxyamines and
nitroxides to give fully reversible frameworks with an adjustable
crosslinking degree and self-healing abilities. Furthermore, we
combined the multifold NER technique with classical NMP to
produce frameworks where the strands could be elongated, as
proven by size exclusion chromatography.[40,41] Simultaneously,
a first route from unsubstituted aromatic core structures to
multifold alkoxyamines was established utilizing triphenylben-
zene as a scaffold. Scheme 1 gives an overview of the necessary
reaction steps consisting of a Friedel-Crafts Acylation, followed
Biphenyl (1a) and terphenyl (2a) were used as ditopic linear
cores, triphenylbenzene (3a) as tritopic trigonal core,
a
tetraphenylmethane (4a) and -ethylene (5a) as tetratopic
square planar and tetrahedral cores, respectively. The variable
sidechains of the alkoxyamines demonstrate the versatility of
the approach and provide alkoxyamines with different sterical
hindrance/dissociation behavior.
We started our investigation by optimization and upscaling
of the synthetic route described in Scheme 1 towards model
alkoxyamine 3j. We intended to identify reaction conditions
that can be readily transferred to other core structures. The
following paragraphs contain a description of each synthetic
step with the conditions applied to the model system and a
discussion of the other scaffolds.
Friedel-Crafts acylation
Initially, the Friedel-Crafts acylation to the model system
precursor 3d was carried out in methylene chloride by mixing
AlCl3 and triphenylbenzene, followed by slow addition of
Scheme 1. Synthetic route to multidimensional alkoxyamines as established
in our group: i) Friedel-Crafts acylation, ii) Reduction with LiAlH4, iii) HBr in
acetic acid, iv) Cu, Cu(II) salt, ligand, TEMPO.
Figure 1. Overview of the synthesized alkoxyamines and intermediate building blocks.
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°
isobutyryl chloride at 0 C. The desired ketone 3d was isolated
in a yield of 72% after recrystallization from acetone. However,
the yield was not robust to small changes of the reaction
conditions, and purification was hindered by the formation of a
polymeric byproduct. Several changes to the procedure,
including solvent and an “inverse addition” of the aromatic core
to the reaction mixture, made it more robust and allowed
synthesis in up to 20 g scale (details see SI). The reaction of
triphenylbenzene with acetyl chloride under the same con-
ditions gave the methyl-substituted ketone 3c with excellent
yield (96% after recrystallization).
Considering the scaffolds of which the ketones were not
obtained or their purification was difficult (1d, 4c/4d, and 5c/
5d), a direct synthetic route to the alcohols was developed
starting from lithiation of the respective bromo precursors and
further conversion with either acetaldehyde or isobutyralde-
hyde (Table 2). This procedure allowed the synthesis of diol 1f
from commercial 4,4’-dibromo-1,1’-biphenyl in 83% yield.
Both tetraphenylmethane derivatives 4e and 4f were
synthesized from tetrakis(4-bromophenyl)methane (4b) accord-
ing to this procedure and gave yields of 42% and 39%,
respectively. Transferring this procedure to 1,1,2,2-tetrakis(4-
bromophenyl)ethylene (5b) leads to the generation of the
desired alcohols 5e (70% yield) and 5f (58% yield) after a
necessary reduction step was performed in the purification (see
SI for details). The yields for all reactions are summarized in
Table 2.
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Transferring this protocol to the biphenyl core yielded the
ketone with methyl sidechain 1c in a yield of 64% (additional
26% of mono-acylated product S2), while the ketone with
isopropyl sidechain 1d was achieved in only 9% yield (addi-
tional 91% yield for the mono-acetylated product S3).
For the terphenyl core, both ketones 2c and 2d could be
synthesized in excellent yield (95% yield for 2c, 92% yield for
2d) and multigram scale (4–5 g). For tetraphenylmethane, only
the methyl sidechains could be introduced to the molecule
(76% yield for the tetra-ketone 4c). We suspect that the lower
reactivity of isobutyryl chloride and a polymeric byproduct that
hindered the purification, as already discovered for triphenyl-
benzene, are responsible. Cross-linking of tetraphenylmethane
under Lewis acid catalysis is literature known, explaining the
polymeric byproduct.[42,43]
Nucleophilic substitution of alcohols to bromides
The conversion of the alcohols to their respective bromides
proved to be straightforward and occurred without any
problems for all synthesized derivatives. The slow addition of
HBr in acetic acid to a premixed and cooled suspension of the
alcohol in methylene chloride gave the bromides in good to
excellent yields (Table 3) and quantities of up to 35 g. However,
it is striking that the methyl sidechain derivatives generally give
a lower yield than the isopropyl chain derivatives.
As expected, acetyl chloride exhibits a higher reactivity than
isobutyryl chloride resulting in higher yields for the acylation
reactions introducing methyl sidechains (Table 1).
Formation of multidimensional-alkoxyamines
Introduction of the hydroxy groups
Previously, we reported the synthesis of the model alkoxyamine
3j based on the Matyjaszewski method, using a Cu/Cu(II)
system with excess of elemental copper, small amounts of the
ligand 4,4’-di-tert-butyl-2,2’-dipyridyl, and an excess of TEMPO
The reductions of the ketones to the alcohols were conducted
with LiAlH4 in dry tetrahydrofuran. In this procedure, the order
of reagents added (LiAlH4, THF, ketone in portions) is crucial to
achieving a high conversion. This procedure allowed the
reduction of the ketones into the respective alcohols in good to
excellent yields and quantities up to 24 g. One attempt to
reduce diketone 1d failed due to a side reaction during workup
(see SI for details).
[16,40]
°
(Table S1) at 75 C.
The original process suffered from
problems during the purification, which was often hindered by
a sticky, polymeric byproduct. Alkoxyamine 3i was already
Table 2. Overview of the alcohol formation via LiAlH4 or direct route via n-
butyllithium.
Table 1. Overview of acylation reactions.
Entry
Pre-cursor
Reagent
Product
R=
Yield
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2
3
4
5
6
7
8
1c
1b
2c
2d
3c
3d
4c
4b
4b
5b
5b
LiAlH4
Isobutyraldehyde
LiAlH4
LiAlH4
LiAlH4
LiAlH4
LiAlH4
Acetaldehyde
Isobutyraldehyde
Acetaldehyde
Isobutyraldehyde
1e
1f
2e
2f
3e
3f
4e
4e
4f
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Methyl
Isopropyl
Methyl
98%
83%
99%
97%
90%
99%
67%
42%
39%
70%
58%
Entry
Pre-cursor
Acyl Chloride
Product
R=
Yield
1
2
3
4
5
6
7
1a
1a
2a
2a
3a
3a
4a
Acetyl chloride
Isobutyryl chloride
Acetyl chloride
Isobutyryl chloride
Acetyl chloride
Isobutyryl chloride
Acetyl chloride
1c
1d
2c
2d
3c
3d
4c
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
64%
9%
93%
92%
96%
72%
76%
9
10
11
5e
5f
Isopropyl
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purification (Table 4). A highly useful side effect of the new
Table 3. Overview of the yields for nucleophilic substitution to the
bromides.
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procedure is that all conversions can be easily determined
visually (Figure 2). A freshly prepared reaction mixture has a
slightly reddish color due to the dissolved TEMPO, and
elemental copper can be seen at the bottom of the vial. During
the reaction, the color changes to dark red first and then to
dark green. At this point in the reaction, the copper was no
longer visible at the bottom of the vial. Upon further stirring,
the green color became brighter and finally turned into
turquoise indicating the end of the reaction.
Reaction times depend on the substrate as was already
reported by Nicolas et al.[17] Derivatives of biphenyl and
terphenyl showed a fast conversion, while derivatives of
triphenylbenzenes and tetraphenylmethanes required several
days and of tetraphenylethylenes one (5i) or two weeks (5j) to
achieve complete conversion. Heating the reaction could have
accelerated the conversion, but at the loss of the favorable mild
conditions, risking elimination. Triphenylbenzene was especially
outstanding in that term. Alkoxyamine 3j formed extremely
Entry
Pre-cursor
Product
R=
Yield
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2
3
4
5
6
7
8
1e
1f
2e
2f
3e
3f
4e
4f
1g
1h
2g
2h
3g
3h
4g
4h
5g
5h
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Isopropyl
72%
84%
90%
91%
80%
81%
72%
94%
71%
89%
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5e
5f
known to literature and synthesized from Suzuki cross-coupling
of a previously prepared alkoxyamine boronic ester and 1,3,5-
tribromobenzene.[21] However, attempts to synthesize alkoxy-
amine 3i following our method failed. Nevertheless, we were
able to isolate and fully characterize the threefold elimination
product 6 in 18% yield (Scheme 2).
We assume that the excess of copper and the comparably
high temperature are responsible for the elimination. Polymer-
ization of the alkene then could have led to the polymeric
byproduct, explaining the difficulties with both syntheses. Thus,
we changed the reaction conditions according to a procedure
reported by Nicolas et al. in 2011.[17] The main changes implied
a) stoichiometric amounts of elemental copper and ligand
without Cu(II) salt, b) only a slight excess of TEMPO, and c)
reaction at room temperature (see Table S1).
Table 4. Overview of the yields for the alkoxyamine formation.
Entry
Precursor
Product
R=
Yield
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2
3
4
5
6
7
8
9
10
1g
1h
2g
2h
3g
3h
4g
4h
5g
5h
1i
1j
2i
2j
3i
3j
4i
4j
5i
5j
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Isopropyl
Methyl
Isopropyl
73%
77%
79%
88%
78%
77%
82%
81%
74%
81%
These mild conditions allowed the synthesis of all multi-
alkoxyamines in good to excellent yield without complicated
Figure 2. The reaction from the bromides to the alkoxyamines has a general
color change from dark red (shortly after start) via dark and light green to
turquoise indicating the end of the reaction. The presented pictures are
exemplary for the formation of alkoxyamine 3j and were recorded on the
day of the start and then every 24 h of the three-day reaction.
Scheme 2. Attempt to synthesize alkoxyamine 3i from 3g resulting in alkene
6 due to threefold elimination.
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°
cooling to give 24.3 g (46.9 mmol, 72% yield) of 1,3,5-tris(4’-
isobutyronylphenyl)benzene of a colorless solid in 72% yield.
slow at room temperature (21 C) so that the reaction was
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°
conducted at slightly elevated temperature (35 C), while
alkoxyamine 3i could not be synthesized at room temperature
at all. Several attempts ended with the formation of a sticky
liquid, most likely the polymerized poly-alkene 6, in the reaction
Rf =0.53 (CH2Cl2).
1H NMR (400 MHz, Chloroform-d [7.27 ppm], ppm) δ=8.12–8.09 (m,
6H, CarH), 7.89 (s, 3H, CarH), 7.83–7.79 (m, 6H, CarH), 3.63 (sept, J=
6.9 Hz, 3H, CH(CH3)2), 1.28 (d, J=6.9 Hz, 18H, CH3); 13C NMR
(100 MHz, Chloroform-d [77.0 ppm], ppm) δ=204.0 (3 C, CO), 144.8
(3 C, Cq), 141.6 (3 C, Cq), 135.4 (3 C, Cq), 129.1 (6 C, CarH), 127.5 (6 C,
CarH), 126.0 (3 C, CarH), 35.5 (3 C, CH(CH3)2), 19.2 (6 C, CH3); EI (m/z,
°
vessel. Starting and stirring the reaction at À 20 C for three days
before warming to room temperature gave the desired alkoxy-
amine 3i in good yield (78%) at last.
+
+
+
°
70 eV, 200 C): 516 (20) [M ], 474 (38) [M À C3H7 +H], 473 (100) [M
À C3H7], 446 (20) [M+À C4H7O+H], 404 (30), 403 (95) [M+
À C3H7À C4H7O+H], 332 (20) [M+À C3H7À 2C4H7O+H]. HRMS-EI (m/z):
[M]+ calcd for C36H36O3, 516.2664; found, 516.2665; IR (ATR, v˜)=
2968 (w), 2931 (w), 2871 (w), 1676 (vs), 1596 (vs), 1561 (w), 1465
(w), 1443 (w), 1408 (w), 1381 (m), 1368 (w), 1350 (w), 1286 (w), 1248
(w), 1220 (vs), 1159 (s), 1119 (w), 1084 (w), 979 (vs), 931 (w), 905 (w),
892 (w), 871 (w), 849 (s), 827 (s), 761 (vs), 721 (w), 697 (s), 669 (w),
663 (w), 640 (w), 620 (w), 608 (w), 572 (w), 521 (w), 490 (m), 455 (w),
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Conclusion
In this report, we present an efficient and scalable synthetic
route to complex multifunctional alkoxyamines starting from
various commercial aromatic building blocks. The versatile
synthetic approach allows us to introduce different side chains
that have an impact on the steric hindrance and dissociation
behavior of the alkoxyamines. The multistep procedure gave
access to linear, trigonal planar, square planar, and tetrahedral
multialkoxyamines. The conditions for the conversion of the
bromides to the alkoxyamines were optimized by implementing
a reliable and mild procedure to give all target structures in
high yield. Furthermore, this synthetic procedure allows a quick
and easy visual estimation of the conversion due to a color
change during the reaction.
446 (w), 435 (w), 418 (w), 407 (w), 395 (w), 377 (w) cmÀ 1
.
The experimental data are consistent with the literature.[40]
1,3,5-Tris(4’-(1’’-hydroxy-2-methylpropyl)phenyl)benzene (3f)
Under an argon atmosphere, lithium;alumanuide (3.53 g,
93.0 mmol, 1.98 equiv.) was suspended in 700 mL of dry THF and
1,3,5-tris(isopropyl 4’-phenyl ketone)benzene (24.3 g, 47.0 mmol,
1.00 equiv.) was added in portions. The reaction mixture was stirred
°
for 19 h at 21 C. Subsequently, the reaction was quenched with
Overall, we developed a synthetic path towards ten rigid,
multidimensional alkoxyamines on five core structures, which
have enormous potential as building blocks in the nitroxide
exchange reaction and/or nitroxide mediated polymerization.
water and 10% NaOH solution was added until everything was
dissolved. The phases were separated and the aqueous phase was
extracted with ethyl acetate. The combined organic phases were
washed with a saturated NaCl solution, dried over Na2SO4 and the
solvent was removed under reduced pressure. The residue was
absorbed in a few mL of an ethyl acetate/cyclohexane mixture (1:1)
and treated in an ultrasonic bath, filtered off, and dried to give
24.3 g (46.5 mmol, 99% yield) of 1,3,5-tris(4’-(1’’-hydroxy-2-meth-
ylpropyl)phenyl)benzene as a colorless solid.
Experimental Section
Following, the synthetic procedures towards the model alkoxy-
amine 3j are given, while full experimental details, analytical data
(1H, 13C, MS, HRMS, IR), and additional comments are given in the
supporting information (SI). The description of reactions and the
original analytical data files can be accessed, examined, and
downloaded from the repository Chemotion (https://www.chemo-
tion-repository.net/) via the DOIs given in the SI.
Rf =0.88 (ethyl acetate).
1H NMR (400 MHz, DMSO-d6 [2.50 ppm], ppm) δ=7.86 (s, 3H, CarH),
7.82–7.79 (m, 6H, CarH), 7.42–7.40 (m, 6H, CarH), 5.14 (d, J=4.4 Hz,
3H, OH), 4.33–4.31 (m, 3H, CHOH), 1.92–1.80 (m, 3H, CH(CH3)2), 0.90
(d, J=6.6 Hz, 9H, CH3), 0.80 (d, J=6.8 Hz, 9H, CH3). 13C NMR
(100 MHz, DMSO-d6 [39.5 ppm], ppm) δ=144.6 (3 C, Cq), 141.5 (3 C,
Cq), 138.4 (3 C, Cq), 127.1 (6 C, CarH), 126.4 (6 C, CarH), 123.8 (3 C,
CarH), 77.2 (3 C, CHOH), 35.0 (3 C, CH(CH3)2), 19.1 (3 C, CH3), 17.9 (3 C,
CH3). FAB (3-NAB, m/z): 523 [M+ +H], 522 [M+], 506 [M+À O], 505
[M+À OH], 480 [M+À C3H7 +H], 479 [M+À C3H7], 433 [M+
À C4H9OÀ CH3À H], 407 [M+À C4H9OÀ C3H7]. HRMS-FAB (m/z): [M+]
calcd for C36H42O3, 522.3134; found, 522.3133; IR (ATR, v˜)=3292
(w), 3247 (w), 3241 (w), 2961 (w), 2925 (m), 2907 (w), 2898 (w), 2868
(w), 2850 (w), 1595 (w), 1513 (w), 1468 (w), 1449 (w), 1384 (m), 1366
(w), 1324 (w), 1275 (w), 1239 (w), 1205 (w), 1033 (s), 1020 (vs), 935
(w), 864 (w), 841 (w), 824 (vs), 792 (s), 761 (w), 727 (w), 722 (w), 705
(m), 662 (w), 646 (w), 636 (w), 612 (m), 579 (s), 555 (w), 538 (w), 504
1,3,5-Tris(4’-isobutyronylphenyl)benzene (3d)
Under an argon atmosphere, aluminum trichloride (34.8 g,
261 mmol, 4.00 equiv.) was suspended in 150 mL of methanedi-
thione. 2-methylpropanoyl chloride (28.4 g, 28.1 mL, 266 mmol,
4.08 equiv.) was added dropwise under ice bath cooling, followed
by 1,3,5-triphenylbenzene (20.0 g, 65.3 mmol, 1.00 equiv.) dissolved
in 250 mL of methanedithione over 1 h, also under ice-bath cooling.
The mixture was stirred under cooling until the end of gas
evolution and then slowly warmed to 21 C. Stirring was repeated
until no significant gas evolution was observed anymore. The
mixture was then heated to 30 C until no further gas evolution was
observed (~2 hours) either. After cooling to 21 C, the supernatant
was decanted from the formed solid and the solid was mixed with
500 g of ice water, 100 mL of conc. HCl and 400 mL of CH2Cl2. This
mixture was stirred until the solid was completely dissolved. The
organic phase was separated, washed with NaOH (10%), water,
saturated NaCl solution, dried over Na2SO4, and the solvent was
removed under reduced pressure. The residue was refluxed in a
mixture of ethanol/ethyl acetate (200 mL/30 mL) and filtered after
°
(m), 401 (w) cmÀ 1
.
°
°
The experimental data are consistent with the literature.[40]
1,3,5-Tris(4’-(1’’-bromo-2-methylpropyl)phenyl)benzene (3h)
To a suspension of 1,3,5-tris(4’-(1’’-hydroxy-2-methylpropyl)phenyl)
benzene (35.2 g, 67.3 mmol, 1.00 equiv.) in 600 mL of methylene
chloride, hydron;bromide in acetic acid (98.1 g, 69.1 mL, 400 mmol,
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NBA, m/z): 941 [M+ +H], 784 [M+À TEMPO], 628 [M+À 2 TEMPO],
488, 472 [M+À 3 TEMPO+H], 471 [M+À 3 TEMPO], 456 [M+À 3
TEMPO-CH3], 441 [M+À 3 TEMPO-2CH3], 158, 157, 156 [TEMPO+],
140 [TEMPO+-O]. HRMS-FAB (m/z): [M+H]+ calcd for C63H94N3O3,
940.7295; found, 940.7293; IR (ATR, v˜)=3002 (w), 2963 (s), 2929
(vs), 2870 (m), 2847 (w), 1596 (w), 1568 (vw), 1510 (w), 1468 (m),
1460 (m), 1375 (m), 1360 (s), 1350 (m), 1313 (w), 1258 (w), 1241 (m),
1208 (w), 1180 (w), 1133 (s), 1079 (w), 1011 (s), 987 (s), 976 (s), 953
(s), 912 (w), 878 (w), 841 (m), 817 (vs), 744 (w), 707 (m), 616 (w), 584
°
5.94 equiv.) was slowly added via a dropping funnel at 0 C. The
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°
reaction mixture was stirred for 3.5 h at 21 C. Afterward, water was
added, the phases were separated and the organic phase was
washed with saturated NaHCO3 solution, water, saturated NaCl
solution, and dried over Na2SO4. The solvent was removed under
reduced pressure. The residue was recrystallized from acetone and
washed with cyclohexane to give 38.9 g (54.7 mmol, 81% yield) of
1,3,5-tris(4’-(1’’-bromo-2-methylpropyl)phenyl)benzene as a color-
less solid.
(w), 557 (w), 507 (w), 452 (w), 424 (w), 375 (w) cmÀ 1
.
1H NMR (400 MHz, Chloroform-d [7.27 ppm], ppm) δ=7.78 (s, 3H,
Car.H), 7.66 (d, J=8.3 Hz, 6H, CarH), 7.49 (d, J=8.3 Hz, 6H, CarH), 4.80
(d, J=8.5 Hz, 3H, CHBr), 2.46–2.34 (m, 3H, CH(CH3)2), 1.25 (d, J=
6.5 Hz, 9H, CH3), 0.94 (d, J=6.6 Hz, 9H, CH3); 1H NMR (400 MHz,
Dichloromethane-d2 [5.32 ppm], ppm) δ=7.82 (s, 3H, CarH), 7.69 (d,
J=8.3 Hz, 6H, Car.H), 7.50 (d, J=8.3 Hz, 6H, Car.H), 4.82 (d, J=8.6 Hz,
3H, CHBr), 2.46–2.34 (m, 3H, CH(CH3)2), 1.24 (d, J=6.5 Hz, 9H, CH3),
0.92 (d, J=6.8 Hz, 9H, CH3); 13C NMR (100 MHz, ppm) δ=141.7 (3 C,
Cq), 141.1 (3 C, Cq), 140.6 (3 C, Cq), 128.4 (6 C, Car.H), 127.3 (6 C, CarH),
125.1 (3 C, CarH), 63.9 (3 C, CHBr), 36.6 (3 C, CH(CH3)2), 21.6 (3 C,
CH3), 20.6 (3 C, CH3); FAB (3-NBA, m/z): 709/711/713/715 [M+ +H]
633/631/629 [M+À Br], 552/550 [M+À 2Br]. HRMS-FAB (m/z): [M+H]+
calcd for C36H4079Br281Br, 711.0660; found, 711.0660; IR (ATR, v˜)=
2959 (m), 2931 (w), 2907 (w), 2867 (w), 1595 (w), 1565 (vw), 1510
(m), 1465 (w), 1445 (w), 1414 (w), 1397 (w), 1384 (m), 1366 (w), 1317
(vw), 1307 (vw), 1244 (w), 1211 (w), 1170 (m), 1120 (w), 1068 (vw),
1018 (w), 942 (w), 928 (w), 887 (vw), 839 (m), 822 (vs), 803 (m), 786
(vs), 771 (m), 744 (m), 707 (m), 669 (vs), 653 (s), 635 (s), 613 (m), 575
9
The experimental data are consistent with the literature.[40]
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Acknowledgments
This research has been funded by the Deutsche Forschungsge-
meinschaft (DFG, German Research Foundation) under Germany's
Excellence Strategy via the Excellence Cluster 3D Matter Made to
Order (EXC-2082/1–390761711), and under the SFB 1176
(259079535) in the context of project C5. I. Wessely thanks the
Carl Zeiss Foundation for the financial support. Furthermore, we
want to thank Angelika Mösle, Lara Hirsch, Pia Lang, and Tanja
Ohmer-Scherrer for their service in the analytical department.
Open access funding enabled and organized by Projekt DEAL.
(m), 534 (w), 507 (w), 476 (w), 452 (vw), 405 (vw) cmÀ 1
.
The experimental data are consistent with the literature.[40]
Conflict of Interest
The authors declare no conflict of interest.
1,1’-(((5’-(4-(2-Methyl-1-((2,2,6,6-tetramethylpiperidin-1-yl)
oxy)propyl)phenyl)-[1,1’:3’,1’’-terphenyl]-4,4’’-diyl)bis
(2-methylpropane-1,1-diyl))bis(oxy))bis
Keywords: Alkoxyamines · Nitroxides · Polymerization · Radical
reactions · Synthetic methods
(2,2,6,6-tetramethyl-piperidine) (3j)
Under an argon atmosphere, 1,3,5-tris(4’-(1’’-bromo-2-meth-
ylpropyl)phenyl)benzene (1.00 g, 1.41 mmol, 1.00 equiv.), 1-oxidan-
yl-2,2,6,6-tetramethylpiperidine (696 mg, 4.46 mmol, 3. 17 equiv.),
copper (134 mg, 2.11 mmol, 1.50 equiv.) and 4-tert-butyl-2-(4-tert-
butylpyridin-2-yl)pyridine (1.13 g, 4.22 mmol, 3.00 equiv.) were
suspended in 30 mL of dry acetonitrile. The reaction mixture was
degassed for 10 minutes by bubbling with argon, before being
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stirred at 35 C for 3 days. Afterward, methylene chloride was
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tetramethylpiperidine) as
a colorless solid. Rf =0.40 (CH2Cl2/
cyclohexane 1:1).
1H NMR (400 MHz, CD2Cl2 [5.32 ppm], ppm) δ=7.84 (s, 3H, CarH),
7.67 (d, J=8.3 Hz, 6H, Car.H), 7.35 (d, J=8.3 Hz, 6H, Car.H), 4.60 (d, J=
5.5 Hz, 3H, CHO), 2.65–2.53 (m, 3H, CH(CH3)2), 1.70–0.97 (m, 45H,
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TEMPO); 13C NMR (100 MHz, CD2Cl2 [54.0 ppm], ppm) δ=142.6 (3 C,
Cq), 140.5 (3 C, Cq), 139.9 (3 C, Cq), 130.0 (6 C, CarH), 126.4 (6 C, CarH),
125.1 (3 C, CarH), 91.5 (3 C, CHO), 60.3 (6 C, Cq TEMPO), 41.2 (6 C, CH2
TEMPO), 35.2 (3 C, CH3 TEMPO), 34.4 (3 C, CH3 TEMPO), 31.8 (3 C, CH
(CH3)2), 20.9 (3 C, CH3 TEMPO), 20.7 (3 C, CH3 TEMPO), 20.6 (3 C, CH3
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Manuscript received: October 26, 2020
Revised manuscript received: November 10, 2020
Accepted manuscript online: November 11, 2020
Eur. J. Org. Chem. 2021, 239–245
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© 2020 The Authors. European Journal of Organic Chemistry published
by Wiley-VCH GmbH