Structurally diverse polyamides obtained from monomers derived via the Ugi multicomponent reaction

Article abstract of DOI:10.1002/chem.201103341

The combination of the Ugi four-component reaction (Ugi-4CR) with acyclic diene metathesis (ADMET) or thiol-ene polymerization led to the formation of poly-1-(alkylcarbamoyl) carboxamides, a new class of substituted polyamides with amide moieties in the polymer backbone, as well as its side chains. 10-Undecenoic acid, obtained by pyrolysis of ricinoleic acid, the main fatty acid of castor oil, was used as the key renewable building block. The use of different primary amines, as well as isonitriles (isocyanides) for the described Ugi reactions provided monomers with high structural diversity. Furthermore, the possibility of versatile post-modification of functional groups in the side chains of the corresponding polymers should be of considerable interest in materials science. The obtained monomers were polymerized by ADMET, as well as thiol-ene, chemistry and all polymers were fully characterized. Finally, ortho-nitrobenzylamide-containing polyamides obtained by this route were shown to be photoresponsive and exhibited a dramatic change of their properties upon irradiation with light.

Full text of DOI:10.1002/chem.201103341

FULL PAPER
DOI: 10.1002/chem.201103341
Structurally Diverse Polyamides Obtained from Monomers Derived via the
Ugi Multicomponent Reaction
Oliver Kreye,[a] Og˘uz TꢀrꢀnÅ,[a] Ansgar Sehlinger,[a] Jenny Rackwitz,[b] and
Michael A. R. Meier*[a]
Abstract: The combination of the Ugi
four-component reaction (Ugi-4CR)
block. The use of different primary
amines, as well as isonitriles (isocya-
nides) for the described Ugi reactions
provided monomers with high structur-
al diversity. Furthermore, the possibili-
ty of versatile post-modification of
functional groups in the side chains of
the corresponding polymers should be
of considerable interest in materials
science. The obtained monomers were
polymerized by ADMET, as well as
thiol–ene, chemistry and all polymers
were fully characterized. Finally, ortho-
nitrobenzylamide-containing polyam-
ides obtained by this route were shown
to be photoresponsive and exhibited
a dramatic change of their properties
upon irradiation with light.
with
acyclic
diene
metathesis
(ADMET) or thiol–ene polymerization
led to the formation of poly-1-(alkyl-
carbamoyl) carboxamides, a new class
of substituted polyamides with amide
moieties in the polymer backbone, as
well as its side chains. 10-Undecenoic
acid, obtained by pyrolysis of ricinoleic
acid, the main fatty acid of castor oil,
was used as the key renewable building
Keywords: metathesis · polyamides ·
polymerization · renewable resour-
ces · Ugi reaction · thiol–ene reac-
tions
Introduction
high yields ranging from 40 to 90%. Due to the high toler-
ance for other functional groups, a broad spectrum of com-
ponents can be applied and thus the Ugi-4CR and related
multicomponent reactions, as well as a range of post-modifi-
cations, are very valuable approaches in combinatorial and
medicinal chemistry for the development of new pharma-
ceuticals.[4] Moreover, the Ugi-4CR has become more and
more attractive in key steps of natural product syntheses.[5]
Wessjohann et al. have shown that the Ugi reaction is a suita-
ble approach in the construction of highly diverse and large
macrocyclic molecules.[6] The application of the Ugi-4CR in
polymer chemistry is to date very limited. Only in 2003 did
Wright et al. describe ring-opening polymerization (ROMP)
with products derived from the Ugi-4CR with norbornenyl
starting materials.[7]
To introduce the Ugi-4CR in the synthesis of highly di-
verse substituted polyamides, a,w-diene monomers were
synthesized by the Ugi reaction and then polymerized by
applying the acyclic diene metathesis (ADMET) polymeri-
zation, as well as thiol–ene addition polymerization. To our
knowledge, the combination of the Ugi-4CR and step-
growth polymerization has not yet been reported. Recently,
we were able to successfully demonstrate the ADMET poly-
merization of 1-(alkylcarbamoyl)alkyl alkanoates (a-carba-
moyl-substituted ester derivatives), derived through the
Passerini-3CR with carboxylic acids and aldehydes contain-
ing terminal double bonds.[8]
Isocyanide-based multicomponent reactions (IMCRs) have
been known since Passerini developed the first three-com-
ponent reaction (Passerini-3CR) between a carboxylic acid,
an aldehyde, and an isocyanide (isonitrile) in 1921.[1] The
best-known and most famous IMCR is the Ugi four-compo-
nent reaction (Ugi-4CR). In 1959, Ugi et al. discovered that
an aldehyde (ketone) and a primary amine react with a car-
boxylic acid and an isonitrile to form substituted a-amino
acylamides.[2] In this reaction two substituted amide groups
are formed under release of one equivalent of water. Thus,
the Ugi-4CR is an atom-economic and environmentally
friendly reaction. It was also shown that water can be used
as the solvent.[3] This reaction is typically performed by stir-
ring the components for approximately 1 day in small quan-
tities of a protic solvent (e.g., methanol or trifluoroethanol).
The desired products are usually obtained in moderate to
[a] Dr. O. Kreye, O. TꢀrꢀnÅ, A. Sehlinger, Prof. Dr. M. A. R. Meier
Laboratory of Applied Chemistry, Institute of Organic Chemistry
Karlsruhe Institute of Technology
Fritz-Haber-Weg 6, Building 30.42, 76131 Karlsruhe (Germany)
Fax : (+49)721-608-46801
E-mail: m.a.r.meier@kit.edu
[b] J. Rackwitz
Institute of Chemistry, Laboratory for Sustainable Organic Synthesis
University of Potsdam
Karl-Liebknecht-Str. 24–25, 14476 Golm/Potsdam (Germany)
A very useful source of the required olefin compounds
are the pyrolysis products of castor oil, which finds a large
number of applications for material syntheses in industry.[9a]
With contents up to 97%, ricinoleic acid 1 ((9Z,12R)-12-hy-
droxyoctadec-9-enoic acid) is the major fatty acid of castor
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103341. It includes full com-
pound characterization (GPC, NMR, and DSC), experimental details,
synthesis procedures, and additional results.
Chem. Eur. J. 2012, 18, 5767 – 5776
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5767

oil triglycerides.[9b] The hydroxyl group of 1 makes this fatty
acid attractive for chemical modifications, such as esterifica-
tion, etherification, and synthesis of polyurethanes and poly-
carbonates from renewable sources. Moreover, the carboxyl-
ic group and the double bond are functionalities to modify
groups, diverse a,w-dienes were successfully applied in the
ADMET polymerization.[10c] In 2001, Warwel et al. de-
scribed renewable high-molecular-weight polyesters that
were prepared by ADMET.[10d,e] Moreover, 2 was also
shown to be a very useful compound for the preparation of
monomers for ADMET polymerization.[10f] In addition, the
10-undecenyl ester of 2 was employed successfully in the
synthesis of castor-oil-derived polymers through ADMET.[10-
1
for favorable material properties.[9a] At temperatures
above 3508C, 1 fragments to 10-undecenoic acid 2 and hep-
tanal 3 (Scheme 1).[9c] Compound 2 is valuable in the chemi-
g–i]
Recently, several reaction conditions, such as time, tem-
perature, and screening of several ruthenium catalysts, as
well as catalyst amounts, were optimized, thereby showing
that 1,4-benzoquinone as additive to ADMET polymeri-
zations can suppress undesired olefin-isomerization side re-
actions dramatically.[11]
Finally, the ADMET strategy was employed in the synthe-
sis of poly-a,b-unsaturated aldehydes starting from the aldol
condensation product of 10-undecenal 4.[12] The results
showed that several ruthenium-based metathesis catalysts
tolerate the a,b-unsaturated double bond during the
ADMET process and no side products were formed. To
expand the applications of 2, we investigated the behavior
of 2 and its reduced product 10-undecenal 4 in IMCRs.
Compound 4 is commercially available in technical quality
at relatively fair prices and can be obtained from 2 or 10-un-
decenol in yields of up to 60% and higher.[13] An improve-
ment in the synthesis of 4 for possible large-scale applica-
tions is, however, still required. Our aim was to introduce 2
and 4 in the Ugi-4CR with different isonitriles and primary
amines, especially amino acid derivatives, to synthesize a li-
brary of a,w-diene derivatives of Ugi products. The behavior
of these products in the ADMET polymerization, as well as
thiol–ene polymerization, another useful tool to polymerize
a,w-diene monomers, will be investigated. Recently, we de-
scribed the thiol–ene polymerization of monomers derived
from renewable sources.[14] Finally, all obtained polymers
were characterized by NMR spectroscopy, gel permeation
chromatography (GPC), and differential scanning calorime-
try (DSC).
Results and Discussion
Scheme 1. Products of thermal fragmentation of ricinoleic acid 1, fol-
lowed by Ugi-4CR and ADMET polymerization.
To create a small library of Ugi-4CR products derived from
10-undecenoic acid 2 and 10-undecenal 4, different primary
amines 5a–5k and isonitriles 6a–6e were used. First, Ugi-
4CRs were performed by using benzylamine 5a and its
para-methoxy-substituted derivative 5b in combination with
commercially available cyclohexyl isonitrile 6a and tert-
butyl isonitrile 6b (Scheme 2, Table 1). After stirring for
about 1 day at room temperature in small amounts of meth-
anol, followed by purification by column chromatography,
the Ugi-4CR products with a,w-diene moieties 7a and 7b
were obtained as light brown oils in rather good yields of 63
and 69%, respectively. Ugi-4CR product 7c was obtained in
a lower yield of 47% from ortho-nitrobenzylamine 5c and
methyl 4-isocyanobutyrate 6c as an ester-functionalized iso-
nitrile. Compound 6c can be synthesized in a three-step pro-
cal industry and has been used for a long time in the synthe-
sis of the renewable polyamide-11.[9d] Recently, olefin meta-
thesis has been shown to be a very useful approach to find
new ways to polymers starting from 2. For instance, olefin
metathesis strategies such as self-metathesis and cross-meta-
thesis of methyl 10-undecenoate with functionalized olefins,
for example, acrylates, allylic alcohols, and acrylonitrile, led
to compounds that are valuable starting materials for step-
growth polymerization reactions to obtain polyesters and
polyamides.[10a,b] Moreover, the ADMET polymerization is
an excellent tool for the polymerization of a,w-diene mono-
mers. Due to the development of modern ruthenium-based
metathesis catalysts, which tolerate numerous functional
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Polyamides Obtained with Monomers via the Ugi Multicomponent Reaction
FULL PAPER
cedure starting from g-aminobutyric acid (GABA). To show
the simplicity of the synthesis of isonitriles from primary
amines, 5c was converted to the corresponding ortho-nitro-
benzyl isonitrile 6e in a two-step synthesis with an overall
yield of 75%.[15] The Ugi-4CR with 5c and 6e gave the a,w-
diene monomer 7d with a yield of 57%. All these products
were extensively characterized by TLC, NMR spectroscopy,
1
and fast atom bombardment (FAB) mass spectrometry. H
and 13C NMR spectra showed double signals, derived from
mixtures of cis/trans-amide-containing products.
In consideration of sustainability, the use of amino acids,
as well as peptides, could be beneficial. Thus, Ugi-4CRs
were also carried out with amino acid methyl ester deriva-
tives of glycine 5d, l- and d-alanine 5e and 5 f, l-valine 5g,
l-phenylalanine 5h, l-serine 5i, and the tert-butyl ester of
glycine 5j. For these compounds, the yields of the obtained
Ugi-4CR products 7e–7m were in all cases above 45% and
reaching up to 69% (7i). For products 7l and 7m, the Ugi-
4CRs were performed with the ester-functionalized isonitrile
6c derived from GABA. All amino acid-derived Ugi-4CR
monomers were unambiguously characterized and it should
be mentioned that the application of chiral amino acid de-
rivatives 5e–5i led to the formation of diastereomers 7g–
7k, which were inseparable by column chromatography on
silica gel. These diastereomers with additional cis/trans-
amide bonds showed complex 1H and 13C NMR spectra.
Nevertheless, in combination with FAB mass spectrometry,
the structure of these a,w-diene monomers was also estab-
lished. Based on the result that l-serine methyl ester with
an unprotected hydroxyl group could be applied successful-
ly, two additional examples with ethanolamine 5k were per-
formed to obtain a,w-diene Ugi-4CR products 7n and 7o in
yields of 54 and 29%, respectively.
In the two final examples, the Ugi-4CR monomers 7p and
7q were synthesized by using 3-butenoic acid 2a as an unsa-
turated short-aliphatic-chain carboxylic acid. This was to
test if a shorter terminal double bond, which is located
closer to the carbonyl group, would have a negative influ-
ence on the ADMET and/or the thiol–ene polymerization in
comparison to 10-undecenoic acid derived a,w-dienes.
All Ugi-4CR monomers were obtained as yellow or light
brown oils in moderate to good yields. The creation of this
small library of monomers by applying 2 and 4 clearly dem-
onstrates the high versatility in the synthesis of a,w-diene
Ugi-4CR products by using different types of primary amine
and isonitrile. Moreover, the application of functionalized
amines and isonitriles provides countless possibilities for
post-modification of the side chains of the monomers and
polymers.
Subsequently, the behavior of the synthesized a,w-unsatu-
rated Ugi-4CR products in the ADMET polymerization was
investigated. It is known that ruthenium-based metathesis
catalysts (Grubbs-type catalysts) tolerate numerous func-
tionalities, but it is also known that nitrogen-containing
functionalities, such as amines, amides, and nitriles, can in-
hibit the catalysts and thus high catalyst loadings are re-
quired.[16] In a catalyst screening, the ruthenium-based olefin
Scheme 2. Ugi-4CR with 10-undecenoic acid 2, 10-undecenal 4, primary
amines 5a–5k, and isonitriles 6a–6e.
Table 1. Products 7a–7q of Ugi-4CRs derived from 2 and 4.[a]
Product
R1
R2
Yield [%]
7a
7b
7c
7d
7e
7 f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p[b]
7q[b]
-Bn (5a)
-cHx (6a)
-tBu (6b)
-(CH2)3CO2Me (6c)
-o-NO2-Bn (6e)
-cHx (6a)
-tBu (6b)
-cHx (6a)
-cHx (6a)
-cHx (6a)
63
69
47
57
55
46
61
68
69
56
51
53
48
54
29
51
40
-p-MeO-Bn (5b)
-o-NO2-Bn (5c)
-o-NO2-Bn (5c)
-Gly-OMe (5d)
-Gly-OMe (5d)
-Ala-OMe (5e)
-d-Ala-OMe (5 f)
-Val-OMe (5g)
-Phe-OMe (5h)
-Ser-OMe (5i)
-Gly-OMe (5d)
-Gly-OtBu (5j)
-(CH2)2OH (5k)
-(CH2)2OH (5k)
-Gly-OMe (5d)
-(CH2)2OH (5k)
-cHx (6a)
-cHx (6a)
-(CH2)3CO2Me (6c)
-(CH2)3CO2Me (6c)
-cHx (6a)
-(CH2)3CO2Me (6c)
-tBu (6b)
-CH2CO2tBu (6d)
[a] Reaction conditions: methanol as solvent, room temperature, 1 day
reaction time. Bn=benzyl, cHx=cyclohexyl. [b] Instead of 10-undeceno-
ic acid 2, 3-butenoic acid 2a was used.
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M. A. R. Meier et al.
metathesis
catalysts
C1
ACHTUNGTRENNUNG(Grubbs I), C2 (Grubbs II), C3
(Hoveyda–Grubbs II), and C4
(Zhan), as well as C5–C7 (M2,
M31, M51) from the company
Umicore, were tested for the
polymerization of a,w-diene
monomer 7i as a model for the
prepared
Ugi
monomers
(Scheme 3). Generally, all cata-
lysts polymerized monomer 7i
at temperatures of 80, 100, and
1208C for 4 h with catalyst
loadings of 1.0 mol% under
a
continuous argon stream
(Table 2). To avoid the well-
known double-bond isomeriza-
tion of ruthenium-based meta-
thesis catalysts during the meta-
thesis process,[11] 1,4-benzoqui-
none (3.0 equiv according to
catalyst amount) as additive
can suppress the isomerization
dramatically.[17] Under neat con-
ditions at 808C the precipitated
polymers P1–P7 possessed mo-
lecular weights in a range be-
tween 3.6 (P1, Grubbs I C1)
and 6.5 kDa (P7, Umicore M51
C7) and polydispersity indices
(PDIs) between 1.6 and 2.4
measured by GPC. In repeated
experiments similar results
were obtained and it was decid- Scheme 3. a) ADMET polymerization of Ugi-4CR product 7i and b) the tested catalysts (Cy=cyclohexyl,
Mes=mesityl).
ed to continue all following
ADMET polymerizations with
the most active catalyst C7.
Furthermore, the polymerization with increased tempera-
tures was investigated and it was found that at 1008C (P8)
slightly higher molecular weights (>7.0 kDa) were obtained,
Table 2. Results of catalyst, temperature, and xylene concentration
screening in ADMET polymerization with Ugi-4CR product 7i.[a]
Polymer
Catalyst
type
Concentration of
T
[8C]
Mn
[gmolÀ1
PDI
Mw/Mn
whereas at 1208C (P12) molecular weights decreased again.
The reason for this seems to be the fast decomposition of
C7 at this high temperature. Moreover, the application of
different solvents in the ADMET polymerization was inves-
tigated. It was observed that under neat conditions the effi-
ciency of stirring is strongly limited within a few minutes
after addition of C7, and thus further polymerization is re-
tarded. Different concentrations of xylene as solvent were
tested at 100 (P9–P11) and 1208C (P13–P15). A remarkable
increase of the molecular weight up to almost 10.0 kDa (P9)
was observed upon applying a concentrated xylene solution
(2.6 molLÀ1) at 1008C with no significant change of the
PDI. The use of more diluted xylene solution tends to result
in lower molecular weights (P10 and P11). The results of
the ADMET polymerization at 1208C showed a similar ten-
dency, but the molecular weights of between 4.8 and
8.0 kDa of the precipitated polymers were significantly
[b]
[b]
xylene [molLÀ1
]
G
]
P1
P2
P3
P4
P5
P6
P7
P8
C1
C2
C3
C4
C5
C6
C7
C7
C7
C7
C7
C7
C7
C7
C7
neat
neat
neat
neat
neat
neat
neat
neat
2.60
1.04
0.52
neat
2.60
1.04
0.52
80
80
80
80
80
3600
3800
5700
4650
5750
4100
6500
7050
9900
8450
7100
6750
7950
4950
4800
1.74
1.82
1.72
1.64
2.38
1.69
1.86
1.98
1.86
1.92
1.93
1.83
1.98
2.02
2.07
80
80
100
100
100
100
120
120
120
120
P9
P10
P11
P12
P13
P14
P15
[a] Reaction conditions: catalysts C1–C7 (1.0 mol%), 1,4-benzoquinone
(3.0 mol%), Ar-purged, 4 h reaction time. [b] Mn and PDI of the precipi-
tated monomer.
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Polyamides Obtained with Monomers via the Ugi Multicomponent Reaction
FULL PAPER
lower (P13–P15). The PDIs of all polymerizations per-
formed with C7 were between 1.8 and 2.1. Based on these
first screening experiments it seemed that optimal results in
ADMET polymerizations of these rather challenging mono-
mers were achieved by using catalyst C7 at 1008C in concen-
trated xylene solutions. These results were then tested in
ADMET polymerizations with other Ugi-4CR monomers.
Subsequently, the ADMET polymerization with a,w-
diene monomer 7a derived from benzylamine was investi-
gated under the optimized conditions at 1008C (Scheme 4).
Surprisingly, the obtained polymers (P16–P21) offered sig-
nificantly higher molecular weights in a range between 7.5
and 18.4 kDa measured by GPC (Table 3). In contrast to the
ADMET polymers derived from 7i, in which the highest
molecular weight polymer was obtained in a concentrated
xylene solution (P9), here more diluted solutions gave the
better results. The polymer derived from a solution of 7a in
xylene (P19) with a concentration of 0.54 molLÀ1 gave the
highest molecular weight with 18.4 kDa. Under neat condi-
tions and concentrated xylene solutions, polymers were also
obtained with considerable molecular weights over 10 kDa
(P16–P18). More diluted solutions ended up with signifi-
cantly lower molecular weight polymers (P20 and P21) with
low PDIs. It thus seems that the side-chain moiety derived
from the primary amine has a strong influence on the be-
havior of the ADMET polymerization. The benzyl group of
7a is obviously better tolerated than the l-valine methyl
ester moiety in 7i. Probably, the unfunctionalized benzyl
group has no interactions with the ruthenium catalyst,
whereas the methyl ester group of l-valine could have a neg-
ative influence on the catalyst.
Finally, a test series in the ADMET polymerization of 7a
was accomplished at 1208C (P22–P25). Here, the highest
molecular weight polymer was achieved in a xylene concen-
tration of 1.08 molLÀ1 with 15.0 kDa. In all cases the mea-
sured PDIs were rather high up to a value of ꢀ3.0. All ex-
periments were repeated and gave identical results.
To further study the ADMET polymerization in xylene
solutions, a,w-diene Ugi-4CR monomer 7 f derived from
glycine methyl ester 5d and tert-butyl isonitrile 6b were
polymerized at 1008C. The achieved polymers P26–P31 all
exhibited low molecular weights between 3.0 and 5.0 kDa
with PDIs ranging from 1.5 to 1.9. The maximum molecular
Scheme 4. ADMET polymerization of Ugi-4CR products 7.
weight was also obtained at
a low concentration of
0.39 molLÀ1.
Table 3. Selected GPC results of ADMET polymerization with Ugi-4CR
To summarize, it seems that the ADMET polymerization
is strongly affected by the Ugi-4CR monomer structure. It is
clear that the structures of amine and isonitrile moieties
play an important role in the activity of catalyst C7. More-
over, the solubility of the different monomers will have a sig-
nificant effect on the polymerization outcome. Thus, a gener-
alization of the ADMET polymerization conditions is im-
possible and each monomer has to be optimized separately.
Nevertheless, all three tested monomers 7a, 7i, and 7 f
were successfully polymerized by ADMET polymerization
to generate a new class of a-alkylcarbamoyl-substituted pol-
ycarboxamides. Furthermore, the polymerization behavior
of other synthesized a,w-diene Ugi-4CR monomers was in-
vestigated. In all following procedures, the ADMET poly-
merizations were tested under neat conditions at 1008C with
1.0 mol% of Umicore catalyst M51 (C7). Monomer 7b, de-
rived from para-methoxybenzylamine 5b and tert-butyl iso-
nitrile 6b gave polymer P32 with a molecular weight of
7.5 kDa and a PDI of 1.8 determined by GPC. Monomers
7c and 7d with ortho-nitrobenzylamine moieties in the side
chain were also polymerized successfully with C7 to obtain
P33 (5400 kDa) and P34 (5900 kDa), respectively. These ex-
amples show the high functional-group tolerance, in this
case nitro groups, of ruthenium-based catalysts. l-Alanine
methyl ester derived monomer 7g was then polymerized to
give poly-1-(alkylcarbamoyl) carboxamide P35 with a molec-
products 7.[a]
Polymer Monomer Concentration of
T
[8C]
Mn
[gmolÀ1
PDI
Mw/Mn
[b]
[b]
xylene [molLÀ1
]
N
]
P16
P17
P18
P19
P20
P21
P22
P23
P24
P25
P26
P27
P28
P29
P30
P31
P32
P33
P34
P35
P36
P37
P38
P39
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7 f
7 f
7 f
7 f
7 f
7 f
7b
7c
7d
7g
7k
7l
neat
2.70
1.08
0.54
0.36
0.27
neat
2.70
1.08
0.54
neat
2.95
1.18
0.59
0.39
0.30
neat
neat
neat
neat
neat
neat
neat
neat
100
100
100
100
100
100
120
120
120
120
100
100
100
100
100
100
100
100
100
100
100
100
100
100
10400
12700
10500
18400
11500
7450
10800
10500
15000
13500
2950
2950
4150
4250
5000
4100
7450
5400
5900
2.43
2.66
2.58
2.83
1.79
1.51
2.45
3.02
2.61
3.01
1.56
1.54
1.73
1.74
1.90
1.71
1.75
1.52
1.59
1.44
14450
no polymer
28800
7550
no polymer
1.74
1.67
7m
7p
[a] Reaction conditions: catalyst C7 (1.0 mol%), 1,4-benzoquinone
(3.0 mol%), Ar-purged, 4 h reaction time. [b] Mn and PDI of the precipi-
tated monomer.
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M. A. R. Meier et al.
ular weight of 14.5 kDa. In contrast, l-serine methyl ester
derived monomer 7k could not be polymerized by ADMET
and resulted only in dimers and trimers. The reason for this
seems to be the primary hydroxyl group of serine. It is
known that primary alcohols inhibit the ruthenium-based
olefin metathesis catalysts during the ADMET process.[18a,b]
Higher catalyst loadings might deliver better results, but
would make the ADMET polymerization less useful and
quite expensive. Recently, we demonstrated that secondary
alcohols are much better tolerated by the ruthenium cata-
lysts.[18c] Thus, a,w-diene monomers with primary hydroxyl
groups in the side chain might have to be protected for a suc-
cessful application in the ADMET polymerization. Surpris-
ingly, monomer 7l with two methyl ester functionalities in
the side chain gave polymer P37 with a high molecular
weight of almost 29.0 kDa, whereas monomer 7m with
almost identical structure (one methyl ester is substituted by
a tert-butyl ester) resulted in polymer P38 with a low molec-
ular weight of 7.5 kDa. There is no explanation for these
dramatic differences in molecular weights and repetitions
gave similar results. Several factors, including the functional-
group tolerance of the catalysts, tendency for ring formation,
crystallization behavior of both monomers and polymers,
and many other factors, will influence these ADMET poly-
merizations and make their outcome quite unpredictable.
Nevertheless, these experiments clearly show that ADMET
of the prepared Ugi monomers is possible and that this
strategy can lead to structurally highly diverse polyamides.
Finally, monomer 7p derived from 3-butenoic acid 2a was
tested in ADMET polymerization to determine if there is
a different behavior in the reaction due to the short-chain
a,w-diene. As expected, the polymerization failed and only
dimers and trimers were obtained (P39). The explanation
for this is most likely the known negative neighboring group
effect (NNGE)[19] because the double bond of the 3-buteno-
ic acid moiety and the amide group are only separated by
one methylene group. The amide group can act as a Lewis
base and coordinate to ruthenium, and thus the inhibition of
the catalyst is the consequence. A possible way to polymer-
ize monomer 7p could be the use of the thiol–ene addition
polymerization instead of ADMET.
Figure 1. 1H NMR spectra (CDCl3, 300 MHz) of monomer 7b, polymer
P32, and polymer with chain stopper P40.
in the ADMET polymerization with 7b, more detailed infor-
mation of the DP and consequently molecular weight could
be obtained by integral correlation of the mentioned signals.
The ADMET polymerization of a,w-diene monomer 7b was
thus performed under neat conditions at 1008C with differ-
ent ratios of 8, ranging from 5.0 to 30.0 mol%, to generate
telechelic polymers P40–P43 (Scheme 5, Table 4). By corre-
lation of the terminal methyl ester signals with the methoxy
group signals of the synthesized telechelic poly-1-(alkylcar-
bamoyl) carboxamides, the DPs and molecular weights of
P40–P43 were determined. As an example, the 1H NMR
spectrum of P40 shows the dominant methyl ester signal at
More information about the degree of polymerization
(DP) of the investigated polymers was obtained by NMR
spectroscopy because no suitable standards are available for
GPC calibration for these novel polymers. The determina-
tion of DPs through direct correlation of integrals by
1H NMR spectroscopy was not possible because the terminal
double bonds were not observed, even in high enlargement.
A very useful approach to determine the DP more exactly
could be the addition of methyl 10-undecenoate 8 as chain
stopper to prepare defined telechelic polymers. A suitable
monomer for this experiment was 7b derived from para-me-
thoxybenzylamine 5b. The methoxy group of 7b is very sig-
1
nificant in the H NMR spectrum with a highly distinctive
singlet signal at 3.77 ppm (Figure 1). Moreover, the methyl
ester signal of chain stopper 8 appears as a singlet at
3.67 ppm. On the assumption that 8 incorporated completely
Scheme 5. ADMET polymerization with monomer 7b and methyl 10-un-
decenoate 8 as a chain stopper.
5772
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Chem. Eur. J. 2012, 18, 5767 – 5776

Polyamides Obtained with Monomers via the Ugi Multicomponent Reaction
FULL PAPER
Table 4. GPC results of ADMET polymerization with Ugi-4CR product
Table 5. Selected DSC results of ADMET polymers derived from Ugi-
4CR monomers.
7b and different amounts of chain stopper 8.[a]
Polymer Amount of Degree of
chain stop- polymerization
Mn (calc.) Mn
PDI
Polymer
Glass transition midpoint [8C]
[b]
A
]
Mw/
P19
P32
P33
P34
P35
P14
P37
P38
P27
À1.4
0.2
36.2
22.1
22.9
À3.1
À11.5
À21.9
À8.8
[b]
[b]
per
ACHTUNGTRENNUNG[mol%]
(DP)
[gmolÀ1
]
Mn
P40
P41
P42
P43
30
20
10
5.0
ꢀ13
ꢀ26
ꢀ41
ꢀ76
7200
4450
6400
7150
7900
1.99
1.82
1.77
1.60
14050
22000
40400
[a] Reaction conditions: catalyst C7 (1.0 mol%), 1,4-benzoquinone
(3.0 mol%), Ar-purged, T=1008C, 4 h reaction time. [b] Mn and PDI of
the precipitated monomer.
P35 (derived from l-alanine) with a higher Tg of 22.98C.
Furthermore, polymers P37 and P38, derived from glycine
methyl and tert-butyl ester, as well as methyl ester function-
alized g-aminobutyric acid as the isonitrile compound, pre-
sented low Tg values of À11.5 and À21.98C, respectively.
Also, the ortho-nitrobenzylamide-substituted polymers P33
and P34 exhibited higher Tg values of 36.2 and 22.18C, re-
spectively, but no melting points were observed.
At length, three monomers of the synthesized Ugi prod-
ucts were chosen to be polymerized through thiol–ene addi-
tion polymerization to establish an alternative polymeri-
zation pathway for these a,w-diene monomers. The radical
thiol–ene addition polymerization of the renewable Ugi
monomers resulted in partly renewable novel polyamides by
a very simple and transition-metal-free procedure. The com-
parison and the discussion of reaction conditions of
ADMET and thiol–ene polymerization for the syntheses of
a number of biodegradable polymers had already been stud-
ied in our group.[9b] Therefore, we performed the polymeri-
zations of the Ugi products 7a, 7i, and 7p by UV-initiated
thiol–ene addition polymerization with butane-1,4-dithiol 9
and 2,2-dimethoxyphenyl acetophenone (DMPA) as photo-
3.67 ppm in comparison to monomer 7b and polymer P32
(Figure 1). These results (Table 4) indicate that the molecu-
lar weights determined by GPC are underestimated in all
cases. The NMR-based calculations indicated remarkable
molecular weights ranging from 7.2 kDa (P40, 30 mol% 8)
up to ꢀ40.0 kDa (P43, 5.0 mol% 8).
Figure 1 displays the 1H NMR spectra of monomer 7b,
the ADMET polymer P32 derived from it, and the corre-
sponding telechelic polymer P40 (30 mol% 8). Monomer 7b
clearly shows the protons of the terminal double bonds at
ꢀ5.00 and 5.80 ppm. In contrast, the signals of terminal
double bonds of polymer P32 disappear completely and
a new multiplet signal is visible at ꢀ5.40 ppm, which corre-
sponds to internal double bonds. The fact that in polymer
P32 no terminal double bonds are detected, even in enor-
mous enlargement, suggests a higher molecular weight than
7.5 kDa as determined by GPC. As mentioned above, tele-
chelic polymer P40 exhibits, in addition to the methoxy
group signal, a significant methyl ester singlet at 3.66 ppm,
derived from chain stopper 8. Due to the fact that both sig-
nals are well separated and no other proton signals appear
in this region, the possibility to determine the DP through
integral correlation is indicated. Nevertheless, it should be
mentioned that macrocycle formation might take place,
which would lead to a misinterpretation of these results.
However, macrocycle formation should be minimal, espe-
cially under bulk conditions and with large amounts of
AHCTUNGTRENNUNG
vent (THF) was necessary to allow stirring of the reaction
monoACHTUNGTRENNUNGfunctional monomer present. Thus, we can indeed
assume that the GPC molecular weights of these polymers
are underestimated.
Finally, all new polymers were characterized by DSC
(Table 5). For all polymers, no melting points were detected,
but glass transition temperatures (Tg) in a range between
À22 (P38) and 238C (P35) were measured. It is clear that
the Tg strongly depends on the side-chain structures derived
from the primary amine and the isonitrile. Similar Tg values
of À1.4 and 0.28C were detected in polymers P19 (derived
from benzylamine) and P32 (derived from para-methoxy-
benzylamine), respectively, which possess related structures.
The amino acid ester derived polymers P14 (derived from l-
valine methyl ester) and P27 (derived from glycine methyl
ester) showed slightly decreased Tg values of À3.1 and
À8.88C, respectively. An exception was observed in polymer
Scheme 6. Thiol–ene addition polymerization of Ugi-4CR monomers 7a,
7i, and 7p.
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5773

M. A. R. Meier et al.
Table 6. GPC calculation results of thiol–ene polymers P44–P46.[a]
magnetically because of the high viscosity. Polymers P44
and P45 exhibited molecular weights of about 7 and 9 kDa,
which are acceptable for some applications (Figure 2a,
Table 6). Compound P46, which offered the lowest molecu-
lar weight of about 3 kDa, could not reach a higher molecu-
lar weight, probably because the olefin functionality is locat-
ed too close to the bulky side groups at which the approach
of a thiol compound was sterically hindered. Because a simi-
lar behavior with only low molecular weight reached for this
monomer was also observed by ADMET, this monomer
might not only be influenced by the negative neighboring
group effect in ADMET, but also by other factors such as
a high tendency of cyclization. 1H NMR analyses of the
polymers proved the expected structures. Furthermore, we
Polymer
Monomer
Mn
[gmolÀ1
PDI
Mw/Mn
Glass transition
midpoint [8C]
[b]
[b]
G
]
P44
P45
P46
7a
7i
7p
8900
7300
3100
1.7
1.6
1.5
1.4
9.6
7.7
[a] Reaction conditions: butane-1,4-dithiol
9
(1.0 equiv), DMPA
(5.0 mol%), THF, Ar-purged, room temperature, 2 h reaction time.
[b] Mn and PDI of the precipitated polymers.
also analyzed the thermal properties of the thiol–ene poly-
mers by DSC (Figure 2b).
None of the samples exhibited any melting transitions on
the second scan and only glass transitions were observed.
When we consider the structure
of the unsaturated monomers,
clearly the existence of the
bulky side groups prevents the
polymer chains from getting
into order, namely crystalliza-
tion, and amide hydrogen
atoms that are able to form hy-
drogen bridges remain hidden
behind bulky cycloaliphatic and
tert-butyl groups. Nevertheless,
the slight shift of glass transi-
tion temperatures can be relat-
ed to the size of those bulky
groups. For instance, the lowest
Tg (P44) could be attributed to
both cycloaliphatic and phenyl
bulky groups located on the
sides of the main chain. Never-
theless, P45 and P46, which
have less pronounced bulky
groups, exhibit higher Tg values
of 9.6 and 7.78C, respectively
(Table 6).
As an application of substi-
tuted polyamides derived by
Ugi reactions, we tested the
cleavage of the photolabile
ortho-nitrobenzyl
group
of
polymers P33 and P34 by irra-
diation. Sung et al. showed in
2008 the cleavage of ortho-ni-
trobenzylamides in small mole-
cules derived from Ugi reac-
tions.[21] In a first try, a solution
of P33 in a mixture of methanol
and THF (1:1) was irradiated
with UV light at l=254 nm
for
approximately
2 days
(Scheme 7). Unfortunately, only
a low level (ꢀ15%) of cleaved
polymer P47 was detected by
1H NMR spectroscopy. In an-
Figure 2. a) GPC traces of thiol–ene polymers P44–P46 and b) DSC thermograms.
5774
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Chem. Eur. J. 2012, 18, 5767 – 5776

Polyamides Obtained with Monomers via the Ugi Multicomponent Reaction
FULL PAPER
Figure 4. DSC thermograms of polymers P33 and P47.
Scheme 7. Photolytic cleavage of ortho-nitrobenzylamide-substituted
polymers P33 and P34 to obtain monosubstituted polymers P47 and P48.
the ortho-nitrobenzyl group started to decompose. In fact,
an additional recorded H NMR spectrum of the thermally
1
other test, the solution of P33 was left outside to be irradiat-
ed by normal sunlight. After 5 days during a sunny period in
springtime, complete cleavage was observed by 1H NMR
spectroscopy after precipitation in hexane (Figure 3). Due
treated polymer P33 showed that the ortho-nitrobenzyl
groups, as well as the methyl ester functionalities, were de-
stroyed completely. These results clearly demonstrate the
change of properties by sunlight irradiation. After cleavage
of the nitrobenzyl group the monosubstituted amide moiety
can form hydrogen bonds and thus the resulting polymer ex-
hibits a high melting point. After further optimization, such
photoresponsive properties could be suitable for material
coatings, ultraviolet lithography techniques, and other appli-
cations.
Conclusion
The Ugi reaction with castor-oil-derived 10-undecenal and
10-undecenoic acid with several primary amines and isoni-
triles led to the formation of a small library of different
poly-1-(alkylcarbamoyl) carboxamides, a new class of highly
substituted a,w-diene amides. The behavior of these mono-
mers was investigated in the ADMET polymerization, as
well as in the thiol–ene addition polymerization. In a catalyst
screening process, we observed that the highest molecular
weights were obtained by applying the catalyst M51 from
Umicore. Moreover, a temperature screening was performed
and the best results regarding high molecular weights oc-
curred at 1008C. Furthermore, the application of ADMET
polymerizations in xylene solutions gave positive results, but
strongly depended on the structure of the monomer used. In
addition to the ADMET polymerization, we demonstrated
that the photoinitiated thiol–ene addition polymerization is
also a very useful tool for the generation of highly substitut-
ed polyamides from Ugi a,w-diene monomers in a transi-
tion-metal-free procedure. Finally, it was possible to demon-
strate the cleavage of the ortho-nitrobenzyl functionality as
an amide protecting group on polymers by irradiation with
sunlight. After cleavage, the polymers exhibited a drastic
change of their properties regarding solubility and thermal
properties. These results indicate interesting application pos-
sibilities as photoresponsive materials.
Figure 3. 1H NMR spectra (CDCl3, 300 MHz) of polymer P33 not treated
with light and sunlight-irradiated polymer P47 after 5 days.
to this encouraging result, polymer P34 was also irradiated
with sunlight under the same conditions. A high conversion
was also detected after 5 days for this reaction. The problem
of the obtained polymer P48 was the complete insolubility
in all common solvents, as is known for polyamides. Polymer
1
P48 was partially soluble in CDCl3 and analysis by H NMR
spectroscopy showed minor signals of the aromatic residue.
To analyze the thermal behavior, DSC thermograms of all
four polymers were measured. The nonirradiated polymers
P33 and P34 exhibited no defined melting points (Tm), but
Tg values at 36.2 (P33) and 22.18C (P34; Table 5). After
light irradiation, the polymers P47 and P48 showed com-
pletely different thermal properties. The DSC analysis indi-
cated no Tg, but clear melting endotherms at Tm =332.2
(P47) and 304.58C (P48; Figure 4). Moreover, the thermo-
gram of P33 showed a strong exothermic signal starting at
2258C and ending at 2908C. Probably at this temperature
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M. A. R. Meier et al.
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highly substituted a,w-diene amide monomers, which can be
successfully polymerized by applying the ADMET or thiol–
ene addition polymerization.
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Chem. Eur. J. 2012, 18, 5767 – 5776