New insights into synthesis and oligomerization of ε-lactams derived from the terpenoid ketone (-)-menthone

Article abstract of DOI:10.1039/c5ra15656d

Two regioisomeric lactams, which are derived from terpenoid ketone (-)-menthone in two steps, are oligomerized in an easy acid-induced procedure to obtain oligoamides that contain alkyl groups and stereocenters; for this, a nucleophilic oligomerization via a non-ionic propagating site (neutral conditions) and a polycondensation are also possible. Furthermore, a regioselective synthesis is demonstrated where (-)-menthone is transformed into one of these lactams in a one-step procedure via Beckmann rearrangement without isolation of any oxime intermediate using the reagent hydroxylamine-O-sulfonic acid (HOSA). These concise oligoamide syntheses smooth the way to novel sustainable long-chain polyamides with highly interesting structures.

Full text of DOI:10.1039/c5ra15656d

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: M. Winnacker, A.
Tischner, M. Neumeier and B. Rieger, RSC Adv., 2015, DOI: 10.1039/C5RA15656D.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 6
RSC Advances
RSC Advances
RSCPublishing
View Article Online
DOI: 10.1039/C5RA15656D
Paper
New Insights into Synthesis and Oligomerization of ε-Lactams Derived from the
Terpenoid Ketone (-)-Menthone
Malte Winnacker, Andreas Tischner, Michael Neumeier and Bernhard Rieger*
Two regioisomeric lactams, which are derived from terpenoid
ketone (-)-menthone in two steps, are oligomerized in an easy
acid-induced procedure to obtain oligoamides that contain
menthone and L-carvone have been transformed to the
corresponding lactones via Baeyer-Villiger oxidation and
polymerized via ring-opening polymerization (ROP) to result in
biorenewable polyesters with highly interesting structures.24,25
In this regard, an increasing research effort is also spent on
developing new ways to sustainable polyamides. These
important polymers are used for a wide range of applications
from high-performance engineering thermoplasts and fibers to
functional materials for biomedical applications.26 In addition to
the “classical” polyamides like polyamide 66 or polyamide 6,
novel biobased polyamides have been developed, based e.g. on
sebacic acid,27 succinic acid,28 brassylic acid29 or abietic acid.30
Ring-opening polymerization (ROP) of ε-caprolactam for the
synthesis of polyamide 6 has been investigated and applied for
decades, where anionic, acid-induced or hydrolytic procedures
can be used.31 Also some special procedures have been
described, e.g. the initiation of polymerization by means of
heterocyclic carbenes.32
alkyl groups and stereocenters; for this,
oligomerization via non-ionic propagating site (neutral
conditions) and polycondensation are also possible.
a nucleophilic
a
Furthermore, a regioselective synthesis is demonstrated where
(-)-menthone is transformed into one of these lactams in a
one-step procedure via Beckmann rearrangement without
isolation of any oxime intermediate using reagent
hydroxylamine-O-sulfonic acid (HOSA). These concise
oligoamide syntheses smooth the way to novel sustainable
long-chain polyamides with highly interesting structures.
1. Introduction
ROP studies with more diversified and/or modified ε-lactams,
which can be obtained from biobased terpenoid ketones, are
still rare but have an immense potential: the resulting
polyamides have a backbone containing side chains and
stereocenters and thus have very interesting structure-
properties-relationships and a high potential for different
applications. Menthone is especially interesting in this context
as it is – on the one hand – a renewable compound which
contains alkyl residues and stereocenters, and – on the other
A key task in modern macromolecular chemistry is the
development of sustainable polymers from renewable
resources.1, 2 This is driven by depleting fossil resources and by
the fact that nature can provide alternative feedstock3 4 and also
- in addition -novel highly interesting building blocks for the
synthesis of innovative polymer architectures for special
applications.5 Famous examples for this fact are, for instance,
the biobased, biodegradable and biocompatible polyester
polylactide that has a lot of applications in material science and
biomedicine,6 cellulose nanofibers,7 or the epoxy resins derived
from epoxidized fatty acids of many plant oils.8 Furthermore,
polyhydroxybutyrate (PHB), which is derived from
microorganisms in its isotactic form,9 is an interesting
biodegradable polymer, which meanwhile is also investigated
synthetically.10 In general, a variety of polymerization methods
and/or the modification of renewable starting materials can be
applied for the preparation of novel sustainable polymers.11
In this context, terpenes are very interesting natural building
blocks,1b,12, 13 which are hydrocarbons that contain one or more
carbon-carbon double bonds. Also, their synthesis and
modification with novel synthetic catalytic14 and enzymatic15
methods, has became an important research field. These
molecules have a carbon skeleton of isoprene (2-methyl-1,4
butadiene) units and a variety of structures and functions.16
Over the last decades, dozens of studies addressing terpene-
based polymers have been published, including polymerization
of myrcene,17 pinene,18 phellandrene19 or of d-limonene-derived
monomers.20 Epoxidized limonene (limonene oxide) has been
used for the synthesis of innovative polycarbonates,21
polyesters22 and polyurethanes.23 Terpenoid ketones L-
hand
– a compound whose precursor (−)-menthol can
meanwhile be synthesized in a large-scale industrial process
starting from the achiral and acyclic compound citral.33
The concept that also biobased terpenoid ketones can be used
for lactam and polyamide synthesis provides a wide range of
possibilities. Accordingly, the transformation of menthone (1) to
the corresponding oxime 234 and then to lactams 3a and 3b has
been described some time ago;35 it was recently shown by our
group that both lactams 3a and 3b can be oligomerized via
anionic ROP (Scheme 1).36,37 For this, the lactam mixture has to
be purified in a time-consuming procedure, either via several
crystallizations or by means of flash chromatography (FC).
Therefore, the aim of this study was developing a remarkably
improved lactam synthesis as well as the application of
enhanced and straightforward oligomerization procedures.
2. Experimental Section
Materials and Methods
All chemicals were purchased from commercial sources (Sigma–

RSC Advances
Page 2 of 6
Aldrich, ABCR) and used as received unless otherwise noted (L-
Removal of the solvent in vacuo provided the crude amino acid,
menthone from Sigma–Aldrich was obtained with 85% isomeric
purity; for clarity, the impurities were isolated via FC and shown
to be other stereoisomers; however, for this study menthone
was used as received, and detailed purification was performed
on the later lactam step). Deuterated solvents for NMR
measurements were obtained from Deutero. NMR spectra were
recorded on Bruker AVIII-300 and Bruker AVIII-500 NMR
spectrometers in CDCl3 for monomers and in trifuoracetic acid
(TFA-d) or – if required in CDCl3 after trifluoroacetylation of the
which was first recrystallized from ethanol and then applied to a
DOWEX 50 WX-2 100-200 ion exchangDeOIc: o10lu.1m03Vn9i.e/wCAA5rRfttiAcel1er5O6n5il6oinDne
exchange chromatography (H2O → 1 M NH4OH) the free amino
acid (1.55 g, 8.28 mmol, 47%) was obtained as a colorless solid.
1H-NMR (300 MHz, D2O): 3.15-3.05 (m, 1H), 2.21-2.11 (dd, 1H),
2.05-1.91 (m, 2H), 1.86-1.65 (m, 2H), 1.61-1.45 (m, 1H), 1.44-
1.30 (m, 1H), 1.25-1.11 (m, 1H), 1.01-0.83 (m, 9H). 13C-NMR (300
MHz, D2O): 182.91, 57.59, 45.13, 31.77, 30.76, 29.39, 26.63,
19.05, 17.33, 16.62. IR (cm-1): 3027.91, 2147.69, 1655.89,
1457.15, 1384.89. MP = 191 °C. Calcd C 64.13, H 11.30, N 7.48,
found C 64.17, H 11.43, N 7.48.
amide bond
-
for polymers. Matrix assisted laser
desorption/ionization - time of flight (MALDI-TOF) spectra were
recorded on a Bruker Ultra Flex TOF/TOF mass spectrometer
using a-cyano-4-hydroxycinammic acid or dithranol as the
matrix. Gel permeation chromatography/size exclusion
chromatography (GPC/SEC) measurements were performed on
an Agilent 1200Series Device with a HFIP gel column and
hexafluoroisopropanole as the solvent and evaluated with PSS
WinGPC software.
Oligomerizations
For lactam oligomerization in vacuo, lactam (M = 169.26 g/mol;
50 mg, 0.3 mmol or – for larger scale - 300 mg, 1.8 mmol) was
placed in a glass ampule, and an initiator was added (for cationic
polymerization: 1 µL or 3 µL of HCl from an Eppendorf pipette;
for nucleophilic oligomerization via non-ionic propagating site:
benzoylated caprolactam (M = 217.26 g/mol; 3 mg; 15 µmol)).
The ampule was subsequently evacuated and sealed with a
torch flame and heated to 250 °C in a sand bath. After a certain
time (4 h or 8 h, respectively), the ampule was opened and the
monomer was washed out several times with a 1:1 hexane/ethyl
acetate mixture. For oligomerization under argon, the
equivalent procedure was performed in a sealed scintillation vial
in a heating block. The remaining residue was analyzed by
GPC/SEC, NMR and MALDI-MS.
Synthesis of Lactams 3a and 3b
A mixture of both lactams 3a and 3b could be obtained from
menthone in two steps using
a previously described
procedure.36 Lactams were separated via FC (gradient
hexane/ethyl acetate) to give pure 3a and 3b, respectively.
For the one-step approach to lactam 3b (“HOSA-route”,
multigram scale) without isolation of oxime intermediates, the
following procedure was applied:38 menthone 1 (1.1 g, 7.13
mmol) was dissolved in formic acid (3.6 mL), hydroxylamine-O-
sulfonic acid (HOSA; 1.2 g, 10.6 mmol) was added and the
mixture was heated under reflux for 6 h. Afterwards the reaction
was quenched with H2O, neutralized with NaOH solution (5%),
extracted with chloroform (three times) and dried over Na2SO4.
The solvent was removed under reduced pressure, and the
remaining residue was recrystallized in hexane and dried in
vacuo (colorless solid; yield 93%).
For polycondensation, amino acid 4 was heated in a sealed glass
ampule for 250 °C for 4 h. The monomer was washed out as
described above and the remaining residue was analyzed. For
copolymerization, ML and CL were mixed in the described ratios,
polymerization was started with 1 mg of aminocaproic acid and
work-up was performed as described for the homopolymers.
1
Oligo-3a: H-NMR (300 MHz, TFA-d): 8.01 (s, 1H), 6.61-6.82 (bs,
1H, repeating unit), 3.62-3.02 (m, 2H, repeating unit), 2.62-2.01
(m, 2H, repeating unit), 2.01-1.51 (m, 4H, repeating unit), 1.49-
1.31 (m, 1H, repeating unit), 1.25-1.13 (m, 1H, repeating unit),
1.11-0.86 (m, 10H, repeating unit). 13C-NMR (500 MHz, TFA-d):
187.35, 56.01, 54.94, 52.89, 51.13, 33.61, 33.10, 28.36, 20.96,
1
3a: H-NMR (300 MHz, CDCl3): δ = 6.03 (bs, 1H), 3.15–2.91 (m,
2H), 2.20–2.03 (m, 2H), 2.12–1.93 (m, 1H), 1.88–1.74 (m, 1H),
1.74–1.52 (m, 1H), 1.51–1.15 (m, 2H), 0.95 (d, J = 6.4 Hz, 6H),
0.88 (d, J = 6.8 Hz, 3H); 13C-NMR (75 MHz, CDCl3): δ = 180.05,
49.71, 48.80, 38.53, 34.73, 28.04, 25.14, 21.50, 20.07, 18.94; MP
= 101 °C; IR (cm-1): 3211.08, 2913.69, 1659.46.; calcd (C10H19NO):
C 70.96, H 11.31, N 8.28, found: C 70.22, H 11.24 N 8.18. αD = -
6.3°; 3b: 1H NMR (300 MHz, CDCl3): δ: 5.66 (bs, 1H), 3.16 (q, J =
9.5, 4.9 Hz, 1H), 2.45–2.21 (m, 2H), 2.01–1.88 (m, 1H), 1.84–1.68
(m, 3H), 1.44–1.17 (m, 2H), 0.99 (d, J = 6.7 Hz, 3H), 0.93 (dd, J =
6.9, 2.0 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ: 58.88, 44.71, 39.07,
32.80, 32.36, 30.20, 24.61, 18.69, 17.90; MP 118 °C. IR (cm-1):
3212.46, 2950.58, 1655.79. calcd (C10H19NO): C 70.96, H 11.31, N
8.28, found C 70.99, H 11.50, N 8.39. αD = - 53.4.
1
20.56, 20.14, 19.80; Oligo-3b: H-NMR (300 MHz, TFA-d): 6.71-
6.31 (m, 1H, repeating unit), 3.82-4.03 (m, 1H, repeating unit),
3.50-3.41 (m, 1H, repeating unit), 2.72-2.30 (m, 1H, repeating
unit), 2.22-1.75 (m, 3H, repeating unit), 1.62-1.21 (m, 3H,
repeating unit), 1.10-0.75 (m, 8H, repeating unit). 13C-NMR (500
MHz, CDCl3 after trifluoroacetylation): 45.41, 32.27, 29.86,
27.39, 20.83, 19.80, 17.78; GPC/SEC data and MALDI-MS spectra
are discussed in the main text. Copolymers oligo-3b-CL (relative
signal intensity depends on the copolymer composition): 1H-
NMR (300 MHz, TFA-d): 3.60-3.41 (m), 2.75-2.59 (m), 2.51-2.25
(m), 1.81-1.61 (m), 1.51-1.31 (m), 1.31-1.20 (m), 1.01-0.81 (m).
Synthesis of amino acid 4
Following a procedure of Imoto et al.35c Mentholactam 3b
(3.00 g, 17.7 mmol, 1.0 eq.) and activated charcoal (750 mg)
were suspended in H2O (30 ml) and concentrated sulfuric acid
(3.0 mL). The reaction mixture was stirred at 125 °C for three
hours. After cooling down to room temperature, the mixture
was neutralized with an excess of barium hydroxide and filtered.
3. Results and Discussion
We could now show that a very fast access to lactam 3b can be
accomplished using the reagent hydroxylamine-O-sulfonic acid
(HOSA). This has been shown to be a reliable reagent for the
synthesis of unsubstituted lactams from ketones and especially
of ε-caprolactam from cyclohexanone.38 Remarkably, this
2

Page 3 of 6
RSC Advances
transformation in formic acid leads to pure 3b directly from 1
without the necessity to isolate any oxime intermediate and/or
to purify a lactam mixture. It is – to the best of our knowledge –
the first time that this terpenoid ketone is directly converted in
such a direct way into its corresponding lactam (Scheme 1). The
1H-NMR spectrum of 3b obtained via this fast route (“HOSA-
route”) equals the one obtained via the two-step synthesis,
where the oximes are isolated first and then transformed to the
lactams with polyphosphoric acid (“polyphosphoric acid–
route”).35c,36 Complete characterization data of all monomers
are described in the supplementary information.
With the aim to use these lactams for a “green” and easy
synthesis of structurally significant oligoamides, we focused on a
cationic (acid-induced with HCl) and a neutral (nucleophilic via
non-ionic propagating site; initiated with N-benzoyl-
caprolactam) procedure (Scheme 1). It is obvious that each of
these procedures by itself provides matter for an own extensive
study with variation of all parameters; however, the aim of this
study was not to cover an extensive number of different
experimental setups, but to elucidate and to emphasize the
potential of these procedures and to evaluate them as
alternatives to the previously described anionic procedure.36
An increased reaction time did not result in a remarkably change
of yield and oligomerization degree (data not VsiehwoAwrtincl)e. OTnhlinise
DOI: 10.1039/C5RA15656D
indicates that an equilibrium between monomers and oligomers
is reached after a certain time. Thus, enhancement of yield and
molecular weight would require a different experimental setup
(e.g. addition of monomer during reaction), which is not possible
with the sealed glass ampoules described here and thus topic of
ongoing investigations.
GPC/SEC measurements were performed for the analysis of the
molecular weight distribution, where - due to the poor solubility
of
oligo-/polyamides
in
common
solvents
-
hexafluoroisopropanol (HFIP) was used as the eluent. The peaks
were then evaluated against a calibration curve to determine
the Mn and Mw values of the oligomers (see table 1 for the
values and supplementary information
( Figure S1) for
elugrams).
In all entries, the GPC traces show a main peak that can be
assigned to the oligo-/polymer. This peak was sometimes
accompanied by a much smaller, low molecular weight peak,
which can be assigned to monomer traces (see elugrams of
monomers for comparison in the SI) or to the cyclic dimer which
is known to be formed in polymerization of substituted ε-
lactams and which is difficult to be removed despite of extensive
washing.39 It is important to mention the difficulty of work-up in
this case: sometimes this low molecular weight peak could only
be removed by washing out by means of sonication, which also
solved partially the oligomers (consider that these oligomers are
better soluble in hexane/ethyl acetate than “normal” polyamide
6, due to their isopropyl and methyl groups in the backbone).
Therefore, a “compromise” had to be found between number of
washing steps and obtained yield of oligomers. With additional
numbers of washing steps (optionally sonication), this low
molecular weight peak could be successively minimized and/or
removed (Figure 1).
ROP
NH
(R)
(S)
N
O
H
O
3a
n
oligo-3a
Cationic (HCl)
or via
O
NOH
non-ionic propagating site (with Bz-CL)
2
1
ROP
O
S
(R)
O
O
OH
(S)
N
H2N
O
NH
H
(HOSA)
O
n
oligo-3b
3b
HCOOH
Scheme 1. Synthesis of lactams 3a and 3b starting from menthone (1)
via oxime (top) or directly and regioselective by means of
2
hydroxylamine-O-sulfonic acid (HOSA; bottom) and ring-opening
polymerization (ROP) to oligo-3a and oligo-3b. Bz-CL = Benzoylated
caprolactam (initiator).
The oligomerizations described in scheme
1 resulted in
oligoamides, while no oligomers were obtained in control
experiments without adding an initiator to the lactams. The
acid-induced oligomerization of 3a and 3b was performed with
conc. HCl at 250 °C in vacuum and sealed glass ampules (Table 1,
entry 1 and 4, which worked better than an acid-induced
Schlenk procedure36) and – additionally – under argon in a
sealed vial in a heating block (Table 1, entry 2 and 5). Further
reactions were initiated only using benzoyl-caprolactam as the
initiator in vacuum ampules (entry 3 and 6). After reaction, the
remaining monomer was washed out with hexane/ethyl acetate
in several washing steps and the remaining oligoamides (beige
residues) were analyzed by gel-permeation chromatography
(GPC/SEC), NMR and matrix-assisted laser desorption ionization
mass spectrometry (MALDI-MS).
Figure 1. GPC/SEC elugram of oligoamides (table 1, entry 4) after
three washing steps (left) and after additional three washing
steps (by means of sonication; right).
While lactam 3a could be shown to oligomerize easier than 3b
with an anionic polymerization procedure,36 this fact could not
necessarily be confirmed with the acid-induced polymerization
procedures described herein, as it can be seen comparing the
molar mass distributions of oligo-3a and oligo-3b (table 1).
Polymerization of 3a under argon works - in terms of the
oligomer length - a bit better than under vacuum (entries 1 and
2), while – at this stage – there is only a marginal difference for
lactam 3b (entries 4 and 5). Interestingly, in both cases it was
not possible to increase yield by increasing reaction time to 8 h
Table 1. Results of the oligomerization of mentholactams 3a and
3b via different procedures.
Entry
Lactam
Conditions
Mn/Mw
Monomer
Conversion
/ Yield
(data not shown). As mentioned, also
a nucleophilic
oligomerization procedure via non-ionic propargating site was
applied, where benzoylated caprolactam was used as initiator,
1
2
3a
3a
HCl, 4h, vac.,
HCl, 4h, ar.
1400/1700
2400/3600
52
which was prepared according to
a literature known
procedure.40 Here, a nucleophilic attack of the lactam at the
endocyclic imide carbonyl carbon occurs, without formation of
an ionic intermediate, followed by stepwise lactam addition.40
Applying this procedure, sterically more hindered lactam 3b
(isopropyl group besides NH) could not be oligomerized under
these conditions, while lactam 3a gave oligomers with Mn values
of around 1000 (entry 5) when the reaction was performed in an
43
3
4
5
6
3a
3b
3b
3b
Bz-CL, 4h, vac.
HCl, 4h, vac.
HCl, 4h, ar.
1000/1100
2300/2500
1800/3400
26
34
31
-
Only
monomer
Bz-CL, 4h, vac.
3

RSC Advances
Page 4 of 6
evacuated ampule. The bimodal character of corresponding GPC
data). It is worth to mention that the tacticity of these
trace (Figure S1, entry 3) is currently topic of ongoing
investigations. Interestingly, neither lactam 3a nor 3b could be
oligomerized so far via this neutral procedure under an argon
atmosphere.
oligomers is pre-defined by the stereochemistry of the
View Article Online
monomers; however, further comments on tacticity based
DOI: 10.1039/C5RA15656D
on 13C spectra cannot be made at this stage with these 13
NMR measurements in TFA-d.
C
For further analysis, matrix-assisted laser desorption ionization
mass spectrometry (MALDI-MS) spectra of the oligoamides were
recorded (Figure 2 and S2). The spectra show a characteristic
peak distance of the monomer unit which is 169.26 and a
maximum oligomer lengths of n=20, as well as a similar molar
mass distribution than the GPC/SEC data, but also with little
differences. Sometimes the GPC/SEC experiments show slightly
higher MWs than the MALDI-MS spectra, which can be
explained with the fact that GPC/SEC is a relative method, but
also with the fact that polyamides with high MW are sometimes
hard to detect in the mass spectrometer (due to unfavorable
“flying behavior”), which is also known from spectra of classical
polyamide 6.41
The successful acid-induced ring-opening oligomerization of
3b raises the question whether – alternatively – this lactam
can be efficiently ring-opened to the corresponding amino
acid 4 and transformed to oligoamides/polyamides via
polycondensation (Scheme 2).
H2SO4
125 °C
OH
O
H2N
NH
O
O
4
3b
250 °C
O
H
N
H
H
n
oligo-3b
Scheme 2. Ring-opening of 3b to 4 and polycondensation of 4 to
oligo-3b.
According to a literature known procedure,35c we obtained
free amino acid 4 by treatment of 3b with concentrated
sulfuric acid / H2O and charcoal. After recrystallization, pure
4 was isolated via an ion exchange column and fully
characterized (SI). Indeed, heating 4 to 250 °C in a sealed
glass ampule resulted in formation of oligoamides, as
determined by GPC/SEC and MALDI. However, the main
part of 4 (ca. 90%) was shown to recyclize to lactam 3b, as
determined by comparing the corresponding NMR spectra.
A series of polycondensation experiments with 4 applying
different reaction times showed that the low yield and an
oligomer lengths of approx. Mn/Mw = 2500/2900 do not
change with time; thus, as expected, improvement here
would also require a modified experimental setup (maybe
also for removing the water formed during reaction).
Figure 2. MALDI-MS spectra of A) oligo-3a and B) oligo-3b
(obtained in entry 1 and 4, table 1).
The NMR spectra of these oligoamides show characteristic
peaks that can be assigned to the defined positions in the
oligomer backbone, as exemplarily shown for entry 2 in
Figure 3 (for further NMR spectra see SI). Due to the poor
solubility in common NMR solvents, TFA-d was used here.
In comparison to the spectra of the monomers, the signals
of the oligomers blur a bit due to the different chain lengths
present. For determination of the oligomerization degree,
the spectra have limited significance, as the oligomers have
only exchangeable H-atoms (NH and OH) as the
“characteristic end-groups”. These can only roughly be used
for end group analysis, when the measurement is done
quickly after solving in solvent TFA-d (these peaks decrease
by time). For the spectrum shown in Figure 3, integration
leads to an average oligomerization degree of ca. 10.
Nevertheless, the GPC data described above are more
reliable for the oligomer length determination in this case.
Figure 4. A) GPC/SEC elugram and B) MALDI-MS spectrum of oligo-
3b obtained via the polycondensation experiment described in
text. Diagonal Line in A) shows calibration masses and limits of
calibration curve (white circles).
Copolymerization behavior of lactams with different
polymerization abilities is another important issue in this
context.37 Thus, we have performed further experiments
addressing the ability of key compound 3b to be (random)
copolymerized with caprolactam (CL; Scheme 3).
1
Figure 3. H-NMR spectrum of oligo-3a (obtained in entry 2, table
1).
H+
O
H
(R)
O
+
O
H
N
(S)
N
OH
n
250 °C
NH
NH
H
The corresponding 13C spectra also show all significant
peaks of the oligoamides (see Figure S3-S16 for all NMR
O
3b
CL
oligo-3b-CL
Scheme 3. Copolymerization of 3b and CL.
4

Page 5 of 6
RSC Advances
corresponding copolymers as well as determination of the
After acid-induced copolymerization, remaining monomers
thermoanalytical data and the exact role of the side groups
View Article Online
were washed out several times as described above, and the
film-like beige residue was analyzed. As expected, 3b shows
lower polymerization ability than CL,37 which could be
demonstrated impressively by the corresponding NMR
spectra. For instance, its copolymerization in a ratio 3b:CL
3:7 leads to a polymer with Mn/Mw = 5200/14300 (PDI =
2.7; Figure 5A). Here, only 10 mol-% of 3b are incorporated
into the polymer backbone, as determined by relative
integration of the peaks in the corresponding spectrum
(Figure 5B; for this, CL-specific signal at 3.55 (representing
2H) and 3b-specific signal at 0.9 (representing 9H) were
used). Decreasing the feed ratio to 3b:CL 1:9 leads to a
copolymer with only 4 mol-% 3b incorporated, while a feed
ratio of 1:1 leads to 22 mol-% of incorporated 3b (Figure
S20).
and stereocenters within the polymer backbone are topics
of ongoing investigations. For the futDuOreI:,1t0h.1e03i9n/vCe5sRtAig15a6t5io6Dn
of kinetic effects in terms of hydrolysis and polymerization
of these modified lactams will also be an important issue.
Notes and References
a
Dr. M. Winnacker, A. Tischner, M. Neumeier, Prof. Dr. B. Rieger,
Technische
Universität
München,
WACKER-Lehrstuhl
für
Makromolekulare Chemie, Lichtenbergstr. 4, 85747 Garching bei
München
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/c000000x/
1
a) R. Mülhaupt, Macromol. Chem. Phys. 2013, 214, 159-174; b) P. A.
Wilbon, F. Chu, C. Tang, Macromol. Rapid Commun. 2013, 34, 8-37; c)
K. Yao , C. Tang , Macromolecules 2013, 46, 1689-1712; d) A. Gandini,
Macromolecules 2008, 41, 9491-9504; e) C. K. Williams, M. A.
Hillmyer, Polym. Rev. 2008, 48, 1-10; f) M. A. R. Meier, J. O. Metzger,
U. S. Schubert, Chem. Soc. Rev. 2007, 36, 1788-1802.
2 A. Gandini , Green Chem. 2011, 13, 1061-1083.
3
P. T. Anastas, N. Eghbali, Chem. Soc. Rev. 2010, 39, 301-312; P. T.
Anastas, M. M. Kirchhoff, Acc. Chem. Res. 2002, 35, 686-694.
4 R. A. Sheldon, Chem. Commun. 2008, 3352-3365.
5
a) S. A. Miller, ACS Macro Lett. 2013, 2, 550-554; b) U. Biermann, U.
Bornscheuer, M. A. R. Meier, J. O. Metzger, H. J. Schäfer, Angew. Chem.
Int. Ed. 2011, 50, 3854-3871.
6 a) A. P. Gupta, V. Kumar, Eur. Polym. J. 2007, 43, 4053-4074; b) A.-C.
Albertsson, I. K. Varma, Biomacromolecules 2003, 4, 1466-1486.
7
S. J. Eichhorn, A. Dufresne, M. Aranguren, N. E. Marcovich, J. R.
Capadona, S. J. Rowan, C. Weder, W. Thielemans, M. Roman, S.
Renneckar, W. Gindl, S. Veigel, J. Keckes, H. Yano, K. Abe, M. Nogi,
A. N. Nakagaito, A. MAngalam, J. Somonsen, A. S. Benight, A.
Bismarck, L. A. Berglund, T. Peijs, J. Mater. Sci, 2010, 45, 1-33.
8
Figure 5. A) Elugram and B) 1H-NMR spectrum of copolymer oligo-3b-CL
(feed 3:7).
a) U. Biermann, W. Friedt, S. Lang, W. Lühs, G. Machmüller, J. O.
Metzger, M. Rüsch gen . Klaas, H. J. Schäfer, M. P. Schneider, Angew.
Chem. Int. Ed. 2000, 39, 2206-2224; b) H. Baumann, M. Bühler, H.
Fochem, F. Hirsinger, H. Zoebelein, J. Falbe, Angew. Chem. Int. Ed.
1988, 27, 41-62.
9
a) Y. Doi, Microbial Polyesters, Wiley-VCH, Weinheim, Germany
Conclusion
1990; b) G. A. M. van der Walle, G. J. M. de Koning, R. A. Weusthuis,
G. Eggink, Properties, Modifications and Applications of Biopolyesters,
Advances in Biochemical Engineering/ Biotechnology, Vol. 71, (Ed: T.
Scheper), Springer, Berlin, Germany 2001, p. 263.
In this study, the two regioisomeric substituted ε-lactams,
which are derived from the terpenoid ketone (-)-menthone,
could be successfully oligomerized via both acid-induced
and neutral ROP procedures. We have also demonstrated
that one of these lactams can be regioselectively
synthesized directly from L-menthone using reagent HOSA.
Thus, concepts that are used for the synthesis of “classical”
polyamide 6 (polycaprolactam, Perlon®) were successfully
transferred to highly interesting biobased lactams which
are derived from a terpenoid precursor. Oligoamides could
be obtained via ROP and polycondensation. A relation was
shown between the applied conditions and the
oligomerization behavior. The polymerizations stopped on
the “oligo-level” despite monomer present, which is
assumed to be caused e.g. by precipitation from bulk. Thus,
variations of the monomer/initiator ratio, polymerizations
in solution, optimizations of these procedures for the
synthesis of higher MW menthone-based polyamides and
10
a) R. Reichardt, B. Rieger, Adv. Polym. Sci 2012, 245, 49-90 (chapter
in: Synthetic Biodegradable Polymers, Springer ISBN 978-3-642-27153-
3); b) M. Zintl, F. Molnar, T. Urban, B. Bernhart, P. Preishuber-Pflügl, B.
Rieger, Angew. Chem. Int. Ed. 2008, 47, 3458-3460.
11
a) K. Schöder, K. Matyjaszewski, K. J. T. Noonan, R. T. Mathers,
Green Chem. 2014, 16, 1673-1686; b) R. T. Mathers, M. A. R. Meier,
Green Polymerization Methods: Renewable Starting Materials, Catalysis
and Waste Reduction, Wiley-VCH, Weinheim, 2011.
12 M. Winnacker, B. Rieger, ChemSusChem 2015, 8, 2455-2471.
13 J. Zhao, H. Schlaad, Adv. Polym. Sci. 2013, 253, 151-190.
14 Q. Zhang, K. Tiefenbacher, Nat. Chem. 2015, 7, 197-202.
15
M. Hofer, H. Strittmatter, V. Sieber, ChemCatChem 2013, 5, 3351-
3357; L. O. Wiemann, C. Falti, V. Sieber, Z. Naturforsch. B 2012, 67,
1056-1060.
16 A. Corma, S. Iborra, A. Velty, Chem. Rev. 2007, 107, 2411-2502.
5

RSC Advances
Page 6 of 6
View Article Online
DOI: 10.1039/C5RA15656D
17
J. M. Bolton, M. A. Hillmyer, T. R. Hoye, ACS Macro Lett. 2014, 3,
717-720.
18
a) N. A. Kukhta, I. V. Vasilenko, S. V. Kostjuk, Green Chem. 2011,
13, 2362-2364; b) H. K. Hall, Jr. J. Org. Chem. 1963, 28, 3213-3214.
19
D. Dakshinamoorthy, A. K. Weinstock, K. Damodaran, D. F. Iwig, R.
T. Mathers, ChemSusChem 2014, 7, 2923-2929.
20 a) M. Firdaus, M. A. R. Meier, Green Chem. 2013, 15, 370-380; b) M.
Firdaus, L. M. de Espinosa, M. A. R. Meier, Macromolecules 2011, 44,
7253-7262.
21
a) F. Auriemma, C. De Rosa, M. R. Di Caprio, R. Di Girolamo, W.
Chadwick Ellis, G. W. Coates, Angew. Chem. Int Ed. 2015, 54, 1215-
1218; b) C. M. Byrne, S. D. Allen, E. B. Lobkovsky, G. W. Coates, J.
Am. Chem. Soc. 2004, 126, 11404-11405.
22 C. Robert, F. de Montigny, C. M. Thomas, Nat. Commun. 2011, 2:586
doi: 10.1038/ncomms1596.
23 M. Bähr, A. Bitto, R. Mülhaupt, Green Chem. 2012, 14, 1447-1454.
24 a) J. Shin, Y. Lee, W. B. Tolman, M. A. Hillmyer, Biomacromolecules
2012, 13, 3833-3840; b) J. Shin , M. T. Martello , M. Shrestha , J. E.
Wissinger, W. B. Tolman, M. A. Hillmyer, Macromolecules 2011, 44,
87-94; c) C. L. Wanamaker, L. E. O´Leary, N. A. Lynd, M. A. Hillmyer,
W. B. Tolman, Biomacromolecules 2007, 8, 3634-3640; d) D. Zhang, M.
A. Hillmyer, W. B. Tolman, Biomacromolecules 2005, 6, 2091-2095.
25
a) J. R. Lowe, M. T. Martello, W. B. Tolman, M. A. Hillmyer, Polym.
Chem. 2011, 2, 702-708; b) J. R. Lowe, W. B. Tolman, M. A. Hillmyer,
Biomacromolecules 2009, 10, 2003-2008.
26 For a good overview see : a) G. W. Becker, D. Braun, L. Bottenbruch,
R. Binsack, Polyamide (Kunstoff Handbuch; 3/4), Hanser Verlag,
Munich, Germany 1998; b) R. S. Lenk, J. Polym. Sci.: Macromol. Rev.
1978, 13, 355-387.
27
L. Jasinska, M. Villani, J. Wu, D. van Es, E. Klop, S. Rastogi, C. E.
Koning Macromolecules 2011, 44, 3458-3466.
28
I. Bechthold, K. Bretz, S. Kabasci, R. Kopitzky, A. Springer, Chem.
Eng. Technol. 2008, 31, 647-654.
29 A. Prieto, I. Iribarren, S. Muñoz-Guerra, J. Mater. Sci. 1993, 28, 4059.
30 S. J. Kim, B. J. Kim, D. W. Jang, S. H. Kim, S. Y. Park, J.-H. Lee, S.-
D. Lee, D. H. Choi, J. Appl. Polym. Sci. 2001, 79, 687-695.
31 a) S. Russo, E. Casazza, Polymer Science: A Comprehensive Reference,
2012, 4, 331-396; b) For a patent, see W. E. Hanford , US Patent
2241322 , 1941.
32
a) S. Naumann, S. Epple, C. Bonten, M. R. Buchmeiser, ACS Macro
Lett. 2013, 2, 609-612; b) S. Naumann, F. G. Schmidt, M. Speiser, M.
Böhl, S. Epple, C. Bonten, M. R. Buchmeiser, Macromolecules 2013, 46,
8426-8433.
33
a) Press release : https://www.basf.com/group/corporate/en/news-and-
media-relations/science-around-us/menthol/story , accessed: July 2014;
b) Press release: BASF adds L-Menthol to product range,
http://www.aroma-ingredients.basf.com/About_us/AboutLmenthol.aspx,
accessed: May 2014.
34
N. Kumar, K. Nepali, S. Sapra, K. Reddy, V. Bijjem, R. Kumar, O. P.
Suri, K. L. Dhar, Med. Chem. Res. 2012, 21, 531-537.
35
a) S. Lochyński, J. Kułdo, B. Frackowiak, J. Holband, G. Wójcik, Tet.
Assym. 2000, 11, 1295-1302; b) N. Komatsu, S. Simizu, T. Sugita, Synth.
Commun. 1992, 22, 277-279; c) M. Imoto, H. Sakurai, T. Kono, J. Polym.
Sci. 1961, L, 467.
36
M. Winnacker, S. Vagin, V. Auer, B. Rieger, Macromol. Chem. Phys.
2014, 215, 1654-1660.
37
For a copolymerization study see: a) J. Kondelíková , J. Šejba, Z.
Černý, J. Králiček, Makromol. Chem., Rapid Commun. 1980, 1, 35-39; b)
J. Kondelíková, J. Šejba, J. Králiček, Z. Smrčková, Die Angew.
Makromol. Chem. 1980, 88, 103-111.
38 G. A. Olah, A. P. Fung, Synthesis 1979, 537-538.
39 H. K. Hall Jr., J. Am. Chem. Soc. 1958, 80, 6404-6409.
40 M. Rothe, E. W. Reinold, Makromol. Chem., Rapid Commun 1991, 12,
313-317.
41
For mass spectrometry data of conventional nylon-6 oligomers in
general see: a) L. Shan, R. Murgasova, D. M. Hercules, M. Houalla, J.
Mass Spectrom. 2001, 36, 140-144; b) H. Choi, E. K. Choe, E. K. Yang,
S. Jang, C. R. Park, Bull. Korean Chem. Soc. 2007, 28, 2354-2358.
6