Amphiphilic polymethacrylate- and polystyrene-based chemical delivery systems for damascones

Article abstract of DOI:10.1002/hlca.200590249

Amphiphilic polystyrene- and polymethacrylate-based β-acyloxy ketones were investigated as potential delivery systems for the controlled release of damascones by retro-1,4-addition in applications of functional perfumery. A series of random copolymers being composed of the hydrophobic damascone-release unit and a second hydrophilic monomer were obtained by radical polymerization in organic solution by using 2,2-azobis[2-methylpropanenitrile] (AIBN) as the radical source (Schemes 2 and 3). A first evaluation of the polymer conjugates in acidic or alkaline buffered aqueous solution, and in the presence of a surfactant, showed that polymethacrylates and polystyrenes having a carboxylic acid function as hydrophilic group are particularly interesting for the targeted applications (Table 2). The release of δ-damascone (1) from polymers with poly(methacrylic acid) and poly(vinylbenzoic acid) comonomers in different stoichiometric ratios was thus followed over several days at pH 4, 7, and 9 by comparison of fluorescence probing, solvent extraction, and particle-size measurements (Tables 3 and 4). In acidic media, the polymers were found to be stable, and almost no δ-damascone (1) was released. In neutral or alkaline solution, where the carboxylic acid functions are deprotonated, the concentration of 1 increased over time. In the case of the polymethacrylates, the fluorescence probing experiments showed an increasing hydrophilicity of the polymer backbone with increasing fragrance release, whereas in the case of the polystyrene support, the hydrophilicity of the environment remained constant. These results suggest that the nature of the polymer backbone may have a stronger influence on the fragrance release than the ratio of hydrophilic and hydrophobic monomers in the polymer chain.

Full text of DOI:10.1002/hlca.200590249

Helvetica Chimica Acta – Vol. 88 (2005)
3089
Amphiphilic Polymethacrylate- and Polystyrene-Based Chemical Delivery
Systems for Damascones
by Damien Berthier, Alain Trachsel, Charles Fehr, Lahoussine Ouali*, and Andreas Herrmann*
Firmenich SA, Corporate R&D Division, P.O. Box 239, CH-1211 Geneva 8
Dedicated to Dr. Ferdinand Näf on the occasion of his 65th birthday
Amphiphilic polystyrene- and polymethacrylate-based b-acyloxy ketones were investigated as potential
delivery systems for the controlled release of damascones by retro-1,4-addition in applications of functional per-
fumery. A series of random copolymers being composed of the hydrophobic damascone-release unit and a sec-
ond hydrophilic monomer were obtained by radical polymerization in organic solution by using 2,2’-azobis[2-
methylpropanenitrile] (AIBN) as the radical source (Schemes 2 and 3). A first evaluation of the polymer con-
jugates in acidic or alkaline buffered aqueous solution, and in the presence of a surfactant, showed that
polymethacrylates and polystyrenes having a carboxylic acid function as hydrophilic group are particularly inter-
esting for the targeted applications (Table 2). The release of d-damascone (1) from polymers with poly(metha-
crylic acid) and poly(vinylbenzoic acid) comonomers in different stoichiometric ratios was thus followed over
several days at pH 4, 7, and 9 by comparison of fluorescence probing, solvent extraction, and particle-size meas-
urements (Tables 3 and 4). In acidic media, the polymers were found to be stable, and almost no d-damascone
(1) was released. In neutral or alkaline solution, where the carboxylic acid functions are deprotonated, the con-
centration of 1 increased over time. In the case of the polymethacrylates, the fluorescence probing experiments
showed an increasing hydrophilicity of the polymer backbone with increasing fragrance release, whereas in the
case of the polystyrene support, the hydrophilicity of the environment remained constant. These results suggest
that the nature of the polymer backbone may have a stronger influence on the fragrance release than the ratio of
hydrophilic and hydrophobic monomers in the polymer chain.
1
.Introduction. – The long-lastingness of fragrance perception is often directly asso-
ciated with the efficiency of perfumed consumer products in body care or household
applications. As a consequence of their high volatility, many attempts to control the
evaporation of fragrances over time have been undertaken to increase their perform-
ance during and after application. As an alternative to encapsulation technologies
(
see, e.g., [1]), the development of chemical delivery systems for the controlled release
of fragrances has become a more and more widely investigated area of research [2]. A
series of precursor molecules, so called ‘pro-fragrances’, have been prepared, and a
broad variety of reaction conditions, such as hydrolysis [3][4] or the change of pH
[
5][6], oxidation [7], the action of temperature, light [8][9], enzymes or microorgan-
isms [10] have been used to trigger the release of perfumery raw materials from their
corresponding precursors.
Recently, damascones (=1-(2,6,6-trimethylcyclohexen-1-yl)but-2-en-1-ones) or
damascenones (=1-(2,6,6-trimethylcyclohexadien-1-yl)but-2-en-1-ones), the so-called
rose ketones [11], were successfully released from different monomeric or dimeric b-
amino, b-acyloxy, b-alkoxy, and b-thio ketones (Scheme 1) [12] by retro-1,4-addition
(retro-Michael-type reaction, see, e.g., [13]). The good performance of these systems
©
2005 Verlag Helvetica Chimica Acta AG, Zürich

3
090
Helvetica Chimica Acta – Vol. 88 (2005)
Scheme 1. Controlled Release of Rose Ketones from b-Acyloxy, b-Alkoxy, and b-Thioketones by retro-1,4-
Addition
in practical applications [14][15] prompted us to investigate the influence of the sub-
strate of the delivery systems on the release of damascones more systematically. Espe-
cially by grafting them onto polymers with different backbone and side-chain struc-
tures, additional advantages such as increased precursor stability (due to the encapsu-
lating polymer matrix), enhanced surface deposition (by specific functionalization of
the polymer) or better dispersion in aqueous media (H O is the main solvent for all tar-
2
geted applications) are expected from polymer conjugates as compared to the ‘mono-
meric’ fragrance-precursor systems described so far [6–10][12]. Previous studies on the
hydrolysis of Schiff bases [3] or the intramolecular cyclization of 2-carbamoylbenzoates
by neighboring-group participation [5][6][16] showed that the fragrance release seems
to be quite sensitive to the structure of the leaving fragrance molecule and to the type of
the polymer, rather than to its actual size or density at the surface.
Polymers are widely used in pharmaceutical applications (for some recent reviews,
see, e.g., [17]) but also increasingly in cosmetics, bodycare or household formulations,
and other products that contain fragrances [1]. In particular, amphiphilic copolymers
and polymer conjugates are of especial interest for the delivery of hydrophobic mate-
rials as a consequence of their formation of aggregates, which even have some mechan-
ical stability (for some recent reviews, see, e.g., [18]). Besides biocompatible poly(ethy-
lene oxide)- or poly(ethylene glycol)-based systems, poly(acrylic or methacrylic acid)
copolymers were investigated; these latter show a pH-dependent change in conforma-
tion and are strongly coiled at low pH and unfolded at higher pH [19]. In most cases,
block copolymers have been studied, and much less is known about the behavior of ran-
dom copolymers, which are often more easily prepared. We thus decided to investigate
the release properties of damascones from amphiphilic poly(ethylene glycol), poly-
(
methacrylic acid), and poly(vinylbenzoic acid) random copolymer conjugates, and to

Helvetica Chimica Acta – Vol. 88 (2005)
3091
compare the release properties from the polymers with those of the corresponding
monomers. Besides the nature of the polymer backbone, the release properties may
be influenced by the structure of the comonomer, as well as by its stoichiometric
ratio with respect to the damascone-release unit.
For the present study, we chose d-damascone (1) [20] as the fragrance molecule to
be released by retro-1,4-addition from polymeric substrates. Due to their ease in prep-
aration and their close structural relationship to the alkanoates and benzoates that have
been investigated previously [12], we synthesized d-damascone derivatives 2 and 3,
which serve as the starting point for polymethacrylate- or polystyrene-based materials,
respectively. Amphiphilic copolymers 4–7 (Fig. 1) with the two different polymer back-
bones can be obtained by radical copolymerization (see, e.g., [21]) of the hydrophobic
monomers 2 or 3 with a second, hydrophilic monomer, such as 8–11 (Fig. 2). Especially
in the case of comonomers 8 and 10, the three-dimensional structure of the resulting
copolymers in aqueous medium will strongly depend on the pH [19]. With the pK of
a
poly(methacrylic acid) and poly(vinylbenzoic acid) homopolymers being 5.0 [22] and
7.1 [23], respectively, a strong difference in polymer conformation is expected for pol-
ymers 4 and 6 when moving from acidic to basic conditions. The pH-dependent proto-
nation and deprotonation of copolymers 4 and 6 and the variation of the molar ratio of
the different comonomers (from 1:1 to 1:5) within the polymer backbone should allow
to influence both, the solubility of the copolymers in aqueous media as well as the
release kinetics of the fragrance molecule. pH-Dependent structural changes are of par-
ticular interest in those types of applications where an increase of pH from acidic to
neutral conditions is observed, as for example in the case of a typical fabric softener.
The behavior of the polymeric delivery systems in aqueous solution is thus particularly
important for the protection of the fragrance molecule during storage (at low pH) as
well as for its release once deposed on the target surface (after a pH-induced structural
change of the polymer at the end of the washing cycle).
2
.Results and Discussion. – 2.1. Preparation of Monomers and Polymers. For the
preparation of polymeric d-damascone precursors, we used (ꢀ)-trans-3-hydroxy-1-
2,6,6-trimethyl-cyclohex-3-en-1-yl)butan-1-one (12) [12][20] as the starting material.
Monomers 2 and 3 were then obtained in one step by reacting butanone 12 (Scheme
) with methacrylic acid (=2-methylprop-2-enoic acid; 8) or 4-vinylbenzoic acid
(
2
(
(
=4-ethenylbenzoic acid; 10) [24], respectively, under N,N’-dicyclohexylcarbodiimide
DCC) coupling conditions [25]. Acid 10 is commercially available, or can easily be pre-
pared in very good yields from 1-chloro- or 1-bromo-4-vinylbenzene by Grignard reac-
tion with CO (dry ice) [24]. Esterification of 10 with 2-[2-(2-methoxyethoxy)-
2
ethoxy]ethanol in the presence of DCC and 4-(dimethylamino)pyridine (DMAP)
gives hydrophilic monomer 11.
Amphiphilic polymethacrylate-based random copolymers 4a–d were prepared in a
two-step sequence by radical polymerization [21][26] in organic solution. In the first
step, monomer 2 was polymerized with 5, 3, 2, or 1 mol-equiv. of tert-butyl methacrylate
as the comonomer by using 2,2’-azobis[isobutyronitrile] (=2,2’-azobis[2-methylpropa-
nenitrile]; AIBN) as initiator. To separate the copolymers 13a–d (Scheme 2) from
unreacted monomers, they were precipitated several times from MeOH or heptane.
Cleavage of the tert-butyl groups with trifluoroacetic acid in CH Cl at room tempera-
2
2

3
092
Helvetica Chimica Acta – Vol. 88 (2005)
Fig. 1. Structures of d-damascone-containing monomers 2 and 3 together with amphiphilic polymethacrylates
and 5 and derived polystyrenes 6 and 7
4
Fig. 2. Structures of hydrophilic comonomers 8–11
ture finally led to the formation of pH-sensitive amphiphilic random copolymers 4a–d,
all of which were obtained as solid materials. Polymers 4a–d could be prepared in one
step from monomers 2 and 8 if the radical polymerization was carried out in dioxane.
The two-step sequence has nevertheless the advantage that intermediates 13a–d are
soluble in THF and can thus be more easily characterized by analytical size-exclusion

Helvetica Chimica Acta – Vol. 88 (2005)
3093
Scheme 2. Preparation of Polymethacrylate-Based Random Copolymers 4, 5, and 13
1
chromatography (SEC). Copolymer 5d ) was obtained in one step by polymerization of
a mixture of 2 and 9 in a ratio of 1:2 and in the presence of AIBN in THF.
1
1
Similarly, polystyrene derivatives 6a ) and 7b,c ), which are structurally closely
related to ‘monomeric’ benzoate 14 [12], were synthesized by random copolymeriza-
tion of 3 with styrene derivatives 10 or 11 in various proportions, respectively, in
THF by using AIBN as the radical source (Scheme 3). Amphiphilic polymers 6a and
7b,c were obtained as solids or highly viscous oils by repetitive extraction or precipita-
tion with heptane.
All polymers were characterized by NMR and IR spectroscopy, and their average
masses were determined by SEC based on a universal calibration with commercially
available poly(methyl methacrylate) (PMMA) or polystyrene (PS) standards in THF.
As mentioned above, the average molecular masses of methacrylates 4a–c could not
be determined with the SEC method described in this work, due to their low solubility
in THF. However, since the hydrolysis of the tert-butyl groups of 13a–d does not mod-
ify the length of the polymer chains, polymers 4a–d should still have the same degree of
1)
For convenience, the key letters a–d of 4a–d indicating the molar ratio of the monomers are also used for
the polymers 5d, 6a, and 7b,c.

3
094
Helvetica Chimica Acta – Vol. 88 (2005)
Scheme 3. Preparation of Polystyrene-Based Random Copolymers 6 and 7
polymerization as their corresponding analogues 13. Table 1 summarizes the measured
average molecular masses (M and M ) as well as the corresponding calculated polydis-
w
n
persity indices (I ). Polymethacrylates 4a–d, 5d and 13a–d were thus found to have
p
average molecular masses between ca. 15000 and 60000 Da and polydispersity indices
of 2.1 to 2.6. The corresponding polystyrene derivatives have much lower molecular
masses varying between ca. 10000 and 15000 Da in the case of 7b,c and 2000 Da for
6
a, with polydispersity indices between 1.3 and 1.8.
13
C-NMR Spectroscopy was found to be the most-convenient technique for the
determination of the molecular structures of the obtained polymers, although consider-
able peak broadening was observed for a series of signals, and not all of the expected
resonances could be clearly assigned. This is particularly true for the carboxylic acid
derivatives 4a–d and 6a. Characteristic peaks at d 211.3 (C=O), 165.4 (ester), 53.3
(
CH ), 41.7 (CH ), or 33.1 (quaternary C) demonstrate the presence of the d-damas-
2 2
cone moiety in the final product. The disappearance of the s and t of the methacrylate
C=C bond of monomers 2, 8, and 9 (at d 136 and 125) or the d and t of the vinylben-

Helvetica Chimica Acta – Vol. 88 (2005)
3095
Table 1. Weight-Average (M
w
) and Number-Average (M ) Molecular Masses as well as Polydispersity Indices (I )
n
p
of Random Copolymers 6a, 7b,c and 13a–d as Determined by Analytical SEC in THF. Polymers 4a–c were
insoluble in THF. All values are rounded up to ꢀ100.
Standard used for universal calibration
M
w
[Da]
M
n
[Da]
I
p
1
3a
b
c
PMMA
PMMA
PMMA
PMMA
PS
47000
35800
54100
56900
2100
18000
16100
26100
24600
1600
2.61
2.22
2.07
2.31
1.31
1.56
1.79
d
6
a
7
b
PS
PS
12100
14700
7700
8200
7
c
zoate C=C bond of monomers 3, 10, and 11 (at d 136 and 116), respectively, show that
remaining monomers could be removed quantitatively in all cases. Furthermore, the
relation of intensities of certain resonances, such as the q at d 19.9 and 59.0 in the
13
C-NMR spectra of polymers 5d and 7b,c, roughly reflects the expected stoichiometric
relationship between the monomer containing the damascone-release unit and the
copolymerized ethylene glycol derivatives.
2
.2. Evaluation of Damascone-Release Properties in the Presence of Surfactants. As a
first evaluation of our delivery systems, we compared the release of d-damascone from
monomers 2, 3, and 14 (Scheme 3) with that of amphiphilic polymers 4–7 under con-
trolled conditions in acidic or alkaline buffered aqueous solution and in the presence
of a nonionic or an anionic surfactant. Surfactants of different type are generally
used in all types of functional-perfumery applications. Despite the fact that the surfac-
tant is likely to influence the damascone release, its presence was expected to provide a
more-realistic impression of the behavior of our delivery systems in practical applica-
tions. Furthermore, the surfactant acts as a solubilizer and thus helps to dissolve both
the hydrophobic monomers and the amphiphilic polymers.
In a typical experiment, 0.25 solutions of the precursors were prepared in THFand
M
added to different buffer solutions in H O/MeCN 2 :1 at pH 4.97 or pH 10.48, contain-
2
®
ing 1% by weight of a nonionic surfactant (Triton X100), or at pH 10.16, containing
1% by weight of an anionic surfactant (sodium dodecyl sulfate (SDS)). After stirring
for 3 d, the reaction solutions were extracted with heptane, and the amount of d-dam-
ascone released was determined by GC with external-standard calibration. To verify
the loss of the damascone during the experiment and to estimate its stability in the buf-
fer solutions, a control experiment with d-damascone was carried out under the same
reaction conditions. Table 2 shows the results obtained for the retro-1,4-reaction of
monomers 2, 3, and 14 and polymers 4–7 in alkaline solution in the presence of surfac-
tants, together with the reference of unmodified d-damascone (1).
The data summarized in Table 2 indicate some interesting aspects for the behavior
of the different release systems in aqueous solution containing a surfactant. The results
obtained for the control sample showed that some of the d-damascone (1) was lost after
3
d in the presence of the nonionic surfactant, independently of the pH and the struc-
ture of the surfactant. The loss of damascone is probably due to the undesired conden-
sation reaction between two damascone molecules under the alkaline conditions (inter-
molecular 1,4-addition).

3
096
Helvetica Chimica Acta – Vol. 88 (2005)
Table 2. Comparison of the Amount [mol-%] of d-Damascone (1) Released by retro-1,4-Addition from Mono-
mers 2, 3, and 14 and from Amphiphilic Polymers 4–7 after 3 d at Room Temperature in Buffered Solutions of
®
H
2
O/MeCN 2 :1 in the Presence of 1% by Weight of Triton X100 or Sodium Dodecyl Sulfate (SDS). All values
were obtained from extraction with heptane and GC analysis with external standard calibration.
Compounds
Amount of d-damascone (1) extracted in the presence of
®
®
Triton X100, pH 4.97
Triton X100, pH 10.48
SDS, pH 10.16
(
phosphate buffer) [mol-%]
(borate buffer) [mol-%]
(borate buffer) [mol-%]
Reference:
Monomers:
1
2
3
4
88
7
2
8
5
3
3
10
83
76
51
98
83
80
61
71
32
26
26
32
1
Polymers:
4a
4
4
4
5
6
7
7
b
c
25
22
24
5
9
15
9
d
d
a
b
c
<1
<1
1
17
5
0
The data in Table 2 show that both the monomeric and polymeric damascone pre-
cursors are relatively stable in acidic media but release the fragrance under alkaline
conditions. The fact that the monomers release the fragrance molecule more easily
than their polymeric analogs indicates that polymers seem to stabilize the release sys-
tems by slowing down the retro-1,4-addition as a consequence of aggregate formation,
as it was originally expected during the design of the polymeric delivery systems (see
above).
At pH 10, polymethacrylic acid derivatives 4a–d show a constant damascone
release of 20–30%, independently of the nature of the surfactant or the stoichiometric
ratio between hydrophobic and hydrophilic units in the polymer backbone, whereas
polystyrene derivatives 6a and 7b,c liberate less than 20% of the fragrance molecule
after 3 d (Table 2). Furthermore, the release properties of the polystyrenes seem to
be more sensitive towards the type of surfactant present (see differences observed
for polymers 6a and 7b,c). The nature of the polymer backbone (polymers 4a–d and
6a), the structure of the hydrophilic comonomer (polymers 6a and 7b,c) and its stoichio-
metric ratio with respect to the hydrophobic damascone-release unit (polymers 7b,c)
are thus important parameters to be considered. As a general trend, higher amounts
of d-damascone (1) were released from copolymers bearing free carboxylic acid func-
tions (4a–d and 6a) as compared to those with the poly(ethylene glycol) side chains (5d
and 7b,c). Especially at high pH, the presence of the negative charge seems to favor the
damascone-release, either as a result of a more-hydrophilic environment close to the
damascone-release unit or a better dispersibility of the polymer system in aqueous
media. Since the overall polymer structure is furthermore pH-dependent [19] (vide
supra), we decided to investigate these phenomena in more detail by comparing the
release of d-damascone from polymers 4a–d and 6a in aqueous solution at different
pH.

Helvetica Chimica Acta – Vol. 88 (2005)
3097
2
.3. Comparison of Damascone Release by Fluorescence Probing and Solvent
Extraction at Different pH. Pyrene is generally used as a probe to explore the hydropho-
bicity or hydrophilicity of aggregates in aqueous systems, since the intensity ratio of the
first (at ca. 272 nm) and the third (at ca. 383 nm) vibronic bands I /I in the fluorescence
1
3
spectrum of pyrene correlates well with the polarity of its direct environment [27–29].
The value of this ratio is 1.59 when the pyrene is solubilized in H O (polar medium),
2
and 0.60 in cyclohexane (apolar medium) [27]. In our case, a ratio of 1.63 was measured
in a buffered aqueous solution at pH 4.0, and a value of 1.82 was obtained at pH 7.0 or
9.0. The conformation of various polymer structures has recently been studied by fluo-
rescence probing with pyrene [19][30][31]. This technique may thus also be useful to
follow conformational changes of our polymeric delivery systems at different pH,
and for the investigation of the damascone release over time. In our systems, the liber-
ation of the damascone in the retro-1,4-reaction generates additional free carboxylic
acid functions on the polymer backbone, and thus increases the polarity of the polymer
with increasing fragrance release. If this change in polarity is sufficiently pronounced,
pyrene may also serve as a probe to follow the damascone release over time. In the case
of quantitative damascone release, pure poly(methacrylic acid) is obtained at the end of
the experiment. As a reference, we measured I /I ratios of 1.14, 1.79, and 1.80 for poly-
1
3
(
methacrylic acid) (2 m
M
) at pH 4, 7, and 9, respectively.
Since the presence of surfactants in aqueous media creates micelles which trap the
hydrophobic pyrene or interact with the polymer [31], the following experiments were
carried out in the absence of surfactants, to avoid the superimposition of different pos-
sible interactions. For the measurements, ca. 2 m
M
solutions of random copolymers 4a–
d and 6a were dissolved in aqueous buffer solutions at pH 4.0, 7.0, and 9.0 and then
ꢁ7
mixed with a solution of pyrene to give a total pyrene concentration of 5 · 10
M
with an EtOH content of 5% in the final solution. For each copolymer, four identical
solutions were prepared, which were analyzed after 0, 24, 48, and 72 h, respectively.
All analyses were carried out in triplicate. For the analysis, the solutions were split
into three parts. One part was used to measure the emission spectra of pyrene, which
was repeated three times. Another part was extracted with heptane and analyzed by
GC, the average value being obtained from three injections; the amount of d-damas-
cone released was determined by external-standard calibration. The remaining part
of the solution served for the measurement of the particle sizes of the aggregates. To
verify that none of the damascone was lost during the extraction, a control experiment
with d-damascone was performed under the same reaction conditions. The results
obtained from the different measurements are summarized in Tables 3 and 4 and illus-
trated in Fig. 3. The deviation between the corresponding intensity peak values I /I
1
3
varied less than 0.05 within the same experiment, and an average deviation of 0.08
was observed between the three measurements. The largest errors were observed at
the beginning of each series (after 1–3 h), which may be due to the fact that the system
had not fully reached equilibrium. In the case of the damascone extractions, an average
error of ca. 3.5% was obtained with a maximum value around 10% (for the styrene
derivatives at pH 9).
The I /I values obtained from the fluorescence spectrum of pyrene at the beginning
1
3
of the experiments reflect the hydrophilic or hydrophobic environment of the pyrene
probe in proximity to the polymer backbone as a function of the pH, the nature of

3
098
Helvetica Chimica Acta – Vol. 88 (2005)
ꢁ7
Table 3. Average I
1
/I
3
Values of Pyrene (5 · 10
M
) Measured at Constant Time Intervals at Room Temperature by
Fluorescence Spectroscopy for Aqueous Solutions of Polymers 4 and 6 (0.2 mM) Buffered at pH 4, 7, and 9.
Average values of three measurements.
Time [h]
1–3
I
1
/I
3
(pH 4)
I
1
/I
3
(pH 7)
1 3
I /I (pH 9)
4
4
4
4
6
a
b
c
1.17 (ꢀ0.08)
1.21 (ꢀ0.01)
1.21 (ꢀ0.01)
1.21 (ꢀ0.01)
1.16 (ꢀ0.16)
1.20 (ꢀ0.17)
1.27 (ꢀ0.08)
1.27 (ꢀ0.08)
1.14 (ꢀ0.11)
1.17 (ꢀ0.12)
1.22 (ꢀ0.01)
1.24 (ꢀ0.01)
1.19 (ꢀ0.11)
1.25 (ꢀ0.01)
1.25 (ꢀ0.00)
1.26 (ꢀ0.00)
1.19 (ꢀ0.06)
1.18 (ꢀ0.03)
1.17 (ꢀ0.02)
1.17 (ꢀ0.03)
1.33 (ꢀ0.09)
1.48 (ꢀ0.02)
1.52 (ꢀ0.05)
1.53 (ꢀ0.04)
1.33 (ꢀ0.27)
1.37 (ꢀ0.27)
1.48 (ꢀ0.20)
1.51 (ꢀ0.16)
1.17 (ꢀ0.10)
1.25 (ꢀ0.12)
1.34 (ꢀ0.02)
1.36 (ꢀ0.03)
1.23 (ꢀ0.09)
1.30 (ꢀ0.02)
1.30 (ꢀ0.02)
1.30 (ꢀ0.00)
1.27 (ꢀ0.11)
1.26 (ꢀ0.04)
1.26 (ꢀ0.05)
1.22 (ꢀ0.06)
1.59 (ꢀ0.09)
1.68 (ꢀ0.01)
1.70 (ꢀ0.04)
1.69 (ꢀ0.02)
1.42 (ꢀ0.24)
1.48 (ꢀ0.23)
1.65 (ꢀ0.08)
1.64 (ꢀ0.02)
1.26 (ꢀ0.10)
1.36 (ꢀ0.12)
1.49 (ꢀ0.05)
1.53 (ꢀ0.07)
1.27 (ꢀ0.09)
1.37 (ꢀ0.01)
1.42 (ꢀ0.02)
1.47 (ꢀ0.05)
1.34 (ꢀ0.09)
1.36 (ꢀ0.01)
1.34 (ꢀ0.06)
1.33 (ꢀ0.05)
2
4
7
4
8
2
1–3
2
4
7
4
8
2
1–3
2
4
7
4
8
2
d
a
1–3
2
4
7
4
8
2
1–3
4
8
2
4
7
2
Table 4. Average Amount [mol-%] of d-Damascone (1) Released at Constant Time Intervals at Room Temper-
ature from Aqueous Solutions of Polymers 4 and 6 (0.2 m ) Buffered at pH 4, 7, and 9. All values were obtained
M
from extraction with heptane and GC analysis with external-standard calibration; average of three measure-
ments.
Time [h]
d-Damascone [mol-%]
pH 4)
(
(pH 7)
(pH 9)
4
4
4
4
6
a
b
c
1–3
1.6 (ꢀ0.7)
2.1 (ꢀ0.7)
2.2 (ꢀ1.0)
2.0 (ꢀ0.5)
0.9 (ꢀ0.5)
1.9 (ꢀ0.8)
2.7 (ꢀ2.0)
2.9 (ꢀ2.2)
1.0 (ꢀ0.4)
1.6 (ꢀ0.5)
1.5 (ꢀ0.5)
1.7 (ꢀ0.6)
1.7 (ꢀ2.1)
1.8 (ꢀ2.2)
1.8 (ꢀ1.6)
1.9 (ꢀ1.8)
1.5 (ꢀ1.2)
2.5 (ꢀ1.4)
3.5 (ꢀ2.2)
2.8 (ꢀ1.8)
3.5 (ꢀ0.4)
14.8 (ꢀ2.6)
18.0 (ꢀ6.8)
22.1 (ꢀ4.2)
1.9 (ꢀ1.0)
8.1 (ꢀ2.6)
10.4 (ꢀ2.3)
14.2 (ꢀ6.5)
2.5 (ꢀ0.4)
8.7 (ꢀ0.5)
12.6 (ꢀ3.0)
14.6 (ꢀ2.8)
1.1 (ꢀ0.3)
8.9 (ꢀ5.4)
11.1 (ꢀ1.5)
16.2 (ꢀ0.8)
4.1 (ꢀ2.8)
8.9 (ꢀ7.6)
11.3 (ꢀ9.7)
12.7 (ꢀ9.8)
4.1 (ꢀ0.4)
16.3 (ꢀ5.3)
22.4 (ꢀ8.0)
23.8 (ꢀ6.5)
2.4 (ꢀ1.1)
12.3 (ꢀ3.7)
13.9 (ꢀ2.2)
22.4 (ꢀ9.2)
3.6 (ꢀ0.6)
13.8 (ꢀ3.0)
18.2 (ꢀ1.1)
27.4 (ꢀ9.6)
1.9 (ꢀ1.0)
9.7 (ꢀ0.6)
14.8 (ꢀ3.1)
22.7 (ꢀ8.8)
7.8 (ꢀ4.9)
11.3 (ꢀ7.6)
15.1 (ꢀ10.3)
19.3 (ꢀ12.5)
2
4
7
4
8
2
1–3
2
4
7
4
8
2
1–3
2
4
7
4
8
2
d
a
1–3
2
4
7
4
8
2
1–3
4
8
2
4
7
2

Helvetica Chimica Acta – Vol. 88 (2005)
3099
1 3
Fig. 3. Comparison of the changes in polarity (determined by fluorescence spectroscopy of pyrene (I /I ))
and the amount of d-damascone [mol-%] released from polymers 4 and 6 at pH 4 (···*···), 7 (- —¤ -), and 9
———) over time. Averages of three measurements.
(
&

3
100
Helvetica Chimica Acta – Vol. 88 (2005)
the polymer, and the stoichiometric ratio of the two monomers within the polymer
backbone.
Concerning the influence of the pH, an increase of I /I can be observed for all pol-
1
3
ymers when the pH varies from 4 to 9 (Fig. 3). This increase is quite strong for polymer
a (from 1.17 to 1.59) and less pronounced for polymethacrylate 4d (from 1.19 to 1.27,
4
Table 3), which is probably due to the presence of copolymer aggregates over the entire
pH range and a partition of pyrene between H O and damascone phases. At pH 4, the
2
values of I /I are almost identical for all the copolymers, which is an indication of their
1
3
hydrophobic character. At this pH, the copolymers form aggregates with strong H-
bonding, which disperse more easily for copolymers 4b and 4c than for copolymer
4d. In the case of 4b, we measured a bimodal size distribution of ca. 520 nm (two
peaks at 135 and 496 nm, resp.) after 1 h at pH 4, whereas polymers 4c and 4d were
found to precipitate in H O. Copolymers 4b–d are more H O-soluble at pH 7 and 9.
2
2
After 3 d, polymer 4d displays a multimodal size distribution at pH 7 and 9, with
peaks centered at 16, 79, and 531 nm. At pH 9, the value of I /I for copolymer 4a
1
3
(
(
1.69) is very close to the value obtained when pyrene is dissolved in the aqueous buffer
1.82). This is presumably due to the high ionization of the carboxylic groups that could
make the polymer shell less permeable to pyrene diffusion.
Analysis of the I /I values of the pyrene spectrum with respect to the stoichiometric
1
3
amount of carboxylic acid comonomers within the polymer chain shows almost con-
stant values at pH 4 varying between 1.14 (4c) and 1.19 (4d). This effect is much
more pronounced at high pH when the acid function is fully deprotonated. In this
case, the corresponding values of I /I increase as the amount of (protonated) carbox-
1
3
ylic acid functions in the polymer backbone increase, and they cover a range from 1.26
(4c) to 1.59 (4a).
Furthermore, the data show that the use of pyrene as the fluorescence probe does
not only allow to observe structural changes of the polymers at different pH but also to
follow the release of damascone over time at constant pH. The increase of the polarity
of the polymer as a consequence of the generation of additional carboxylic acid func-
tions during the retro-1,4-reaction is reflected by an increase of the I /I values of the
1
3
pyrene in the case of methacrylate derivatives 4a–d. This effect is more pronounced
at higher pH where more damascone is released than at a lower pH where the polymer
is stable. As an example, after 72 h, an increase of I /I of 0.27 (from 1.26 to 1.53) was
1
3
observed for polymer 4c at pH 9 as compared to an increase of 0.10 (from 1.14 to 1.24)
at pH 4 (Table 3). Extraction data revealed a release of d-damascone of 27% in the for-
mer and 2% in the latter case (Table 4). In contrast to the polymethacrylates 4a–d, the
I /I values of polystyrene derivative 6a remain quite stable during damascone release
1
3
at pH 4, 7, and 9.
At the beginning of the experiment, polymers 4a–d form suspensions in acidic or
alkaline media. With the exception of 4b, size measurements revealed the presence
of particles with a diameter above 1 mm under acidic conditions. Homogeneous disper-
sions are obtained the more the polymer is hydrophilic, the larger the aggregates, and
the higher the pH. Polymer 4d self-assembles at neutral pH to give particles with a
diameter ranging between 2300 (after 1 h) and 756 nm (after 3 d, bimodal distribution).
At a given pH, the stability increases with increasing damascone release. The same pol-
ymer is soluble in alkaline solution with an average particle size of ca. 16 nm (multi-

Helvetica Chimica Acta – Vol. 88 (2005)
3101
modal distribution in intensity). At pH 9, size measurements showed aggregates rang-
ing between 560 (after 1 h) and 670 nm (after 3 d), with a constant size distribution dur-
ing the experiment. This indicates a high stability of the styrene copolymer aggregates
as compared to the corresponding methacrylates, and predicts a lower damascone
release. Although extraction data showed that this is not the case, it should, however,
be noted that solvent extraction disturbs the equilibrium by removing the damascones
from the aqueous phase. It may also be possible that, in practical applications, the stron-
ger hydrophobicity of the polymer gives rise to a stronger retention of the damascone
inside the polymer, and thus slows down its evaporation (out of the polymer matrix) as
compared to the corresponding methacrylates. Indeed, the direct comparison of poly-
mer conjugates 4a and 6a by an expert panel in a fabric-softener application revealed
that a lower intensity of d-damascone was detected for the sample containing the poly-
styrene derivative. Nevertheless, this aspect needs further experimental investigation.
Interestingly, the stoichiometric ratio of damascone-release units and carboxylic
acid comonomers in the polymer backbone does not seem to have a strong influence
on the release of the damascone, as shown by solvent extraction. In all cases, yields
between ca. 20 and 30% were obtained at the end of the experiment (Table 4). These
values are within the same order of magnitude as the data obtained from the extrac-
tions carried out in the presence of surfactants (Table 2), with the exception of polystyr-
ene 6a, where about double the amount of d-damascone was released as compared to
®
the preceding experiment (in the presence of Triton X100).
Although a quantitative correlation of the fluorescence and extraction data is not
straightforward, Fig. 3 shows that there is a reasonably qualitative fit of the curves
obtained from the two techniques. The constant values obtained for the I /I values
1
3
in the pyrene spectrum in the presence of polystyrene derivative 6a may be explained
by the more hydrophobic character of the polymer as compared to the corresponding
polymethacrylates 4a–d. The release of the damascone has much less influence on the
variation of I /I values, which may be due to a higher retention of the released damas-
1
3
cone in proximity of the polymer or to a preferred interaction of the pyrene with the
aromatic groups of the polystyrene backbone.
3
.Conclusions. – Damascones were successfully released from their polymeric b-
acyloxy ketone derivatives by retro-1,4-addition under neutral or alkaline reaction con-
ditions. A series of amphiphilic polymethacrylate- (see 4a–d and 5d) and polystyrene-
(
see 6a and 7b,c) based random copolymers were prepared by free radical polymeriza-
tion of hydrophobic damascone derivatives 2 and 3 with hydrophilic comonomers 8–11
in various ratios by using AIBN as the radical source.
The release of d-damascone (1) from various polymers was investigated in buffered
aqueous solution in the presence and absence of surfactants and compared to that of
the corresponding monomers by organic-solvent extraction. Whereas the monomers
release damascones quite rapidly, the polymeric structures considerably slowed down
the damascone release. Polymethacrylates and polystyrenes having a carboxylic acid
function as hydrophilic group were found to be of particular interest for the targeted
applications. In acidic media, both the monomers and the polymers were stable, and
almost no damascone was released. In the case of polymethacrylates 4a–d and poly-
styrene 6a, an average of 20–30% of damascone release was measured after 3 d at

3
102
Helvetica Chimica Acta – Vol. 88 (2005)
pH 9. The rate of damascone release can be influenced by a variety of structural param-
eters such as the nature of the polymer backbone, the structure and stoichiometry of the
amphiphilic comonomer with respect to the damascone-release unit, and the polymer
conformation in solution. Whereas the liberation of d-damascone from polymethacry-
lates 4a–d seems to be only pH-dependent, the release properties of the polystyrenes
vary with the type of surfactant present (see differences observed for polymers 6a and
7b,c), the nature of the polymer backbone (polymers 4a–d and 6a), the structure of the
hydrophilic comonomer (polymers 6a and 7b,c) and with the ratio between hydropho-
bic and hydrophilic repeat units in the polymer (polymers 7b,c). Generally, an increas-
ing hydrophilicity of the polymer backbone increases the amount of damascone
released.
Using pyrene as a fluorescence probe permitted an investigation of the hydrophilic-
ity or hydrophobicity of the polymer backbone as a function of the pH, and, due to the
fact that the liberation of the damascone generates additional carboxylic acid functions
on the polymer backbone, this technique also allowed us to follow the damascone
release over time at constant pH.
As a result of the deprotonation of the carboxylic acid functions in polymers 4a–d
and 6a with increasing pH, an increase of I /I can be observed for all polymers when
1
3
the pH varies from 4 to 9 (Fig. 3). The increase of the polarity of the polymer as a con-
sequence of the generation of additional carboxylic acid functions during the retro-1,4-
reaction is reflected by an increase of the I /I values of the pyrene in the case of meth-
1
3
acrylate derivatives 4a–d. This effect is even more pronounced at higher pH where
more damascone is released than at lower pH where the polymer is stable. In the
case of polystyrene derivative 6a, the I /I value of the pyrene spectrum remains con-
1
3
stant over time, indicating the more-hydrophobic environment of the polymer back-
bone, and thus better retention of the pyrene in proximity of the polymer. The fact
that at pH 9 a comparable amount of d-damascone was released from polymers 4a–
d and 6a suggests that the d-damascone may be more strongly retained inside the
more-hydrophobic polymer matrix of 6a, and thus results in a slower evaporation
once deposited onto a surface. Preliminary tests in practical applications seem to con-
firm this hypothesis, thus suggesting that the nature of the polymer backbone has a
stronger influence on the fragrance release than the ratio of hydrophilic and hydropho-
bic monomers within the polymer chain.
Experimental Part
General. Commercially available reagents and solvents were used without further purification if not stated
otherwise. Reactions were carried out in standard glassware under N
Demineralized H O was obtained from a Millipore-Synergy-185 water purifier. Column chromatography
CC): silica gel 60 (32–63 microns, from Chemie Brunschwig). Melting points: Büchi-B540 melting-point instru-
2
or Ar, and yields were not optimized.
2
(
ment, at 18/min; uncorrected. Fluorescence spectra: Instruments-SA-Flurolog-3 spectrofluorimeter; 1-cm quartz
cuvettes. Size measurements: Malvern Zetasizer NanoSeries; diameters in nm with diffusion at 365 nm. IR Spec-
ꢁ
1
1
13
tra: Perkin-Elmer-1600-FTIR spectrometer; ~n in cm . H- and C-NMR Spectra: Bruker-DPX-400 spectrom-
eter; d in ppm downfield from Me Si as internal standard, J in Hz. GC/EI-MS: HP-5890 or -6890 GC system
4
equipped with a Supelco-SPB-1 capillary column (30 m, 0.25 mm i.d.) at 708 for 10 min then to 2608 (108/
min), helium flow ca. 1 ml/min, coupled with a HP-MSD-5972 or -5973 quadrupole mass spectrometer, electron
energy ca. 70 eV; fragment ions in m/z (rel. int. in % of the base peak).

Helvetica Chimica Acta – Vol. 88 (2005)
3103
Analytical Size-Exclusion Chromatography (SEC). SEC Analyses were performed at r.t. (ca. 228) with a
system composed of a ThermoFinnigan-Surveyor vacuum online degasser, quaternary LC pump, autosampler,
and UV/VIS detector, combined with a ThermoSeparationProducts (tsp) Spectra-System-IR-150 refractometer
and a Viscotek-270-Dual-Detector viscometer. Samples were eluted from a Macherey-Nagel-Nucleogel-GPC-
1
04-5 column (300×7.7 mm i.d., particle size 5 mm) at a flow rate of 1.0 ml/min by using HPLC-grade THF
from SDS (France). Universal calibrations were carried out with the viscometer and the RI detector using com-
mercial polystyrene (PS) or poly(methyl methacrylate) (PMMA) polymer standards from Fluka. Ca. 40 mg of
the polymer standards were precisely weighed and dissolved in 10 ml of solvent, then 50 ml of these solns. were
injected for the calibration.
(
ꢀ)-trans-3-Hydroxy-1-(2,6,6-trimethylcyclohex-3-en-1-yl)butan-1-one (12) can be prepared according to
several methods [12][20].
-Ethenylbenzoic Acid (10) [24]. A Grignard reagent prepared from freshly distilled 1-bromo-4-ethenyl-
benzene (11.00 g, 60.1 mmol), Mg turnings (1.58 g, 66.1 mmol), and a crystal of I in dry THF (150 ml) was
poured slowly (!) onto dry ice. The mixture was extracted with Et O (200 ml, 2×), washed with 10% HCl
soln. (100 ml, 2×), and with a sat. NaCl soln. (100 ml, 2×). Re-extraction of the aq. phases with Et O, drying
), and concentration gave 8.29 g (93%) of 10. White solid. M.p. 140–1428. H-NMR (400 MHz,
): 12.56 (br. s , 1 H); 8.07 (d, J=8.2, 2 H); 7.47 (d, J=8.7, 2 H); 6.75 (dd, J=17.4, 10.8, 1 H); 5.88 (d,
4
2
2
2
1
(
Na
CDCl
J=17.4, 1 H); 5.39 (d, J=11.3, 1 H). C-NMR (100.6 MHz, CDCl
2 4
SO
3
1
3
3
): 172.37 (s); 142.83 (s); 135.96 (d); 130.57
+
+
(d); 128.43 (s); 126.22 (d); 116.95 (t). EI-MS (commercial sample): 149 (10, [M+1] ), 148 (100, M ), 132 (9),
1
31 (85), 120 (3), 104 (4), 103 (34), 102 (9), 91 (3), 78 (3), 77 (22), 76 (4), 75 (4), 74 (4), 63 (3), 51 (9), 50 (5).
-[2-(2-Methoxyethoxy)ethoxy]ethyl 4-Ethenylbenzoate (11). A soln. of 10 (2.00 g, 13.5 mmol), DMAP (1.30
2
g, 10.8 mmol), and 2-[2-(2-methoxyethoxy)ethoxy]ethanol (3.30 g, 20.3 mmol) in CH
an ice bath prior to the dropwise addition of a soln. of DCC (3.10 g, 14.9 mmol) in CH
2
Cl
2
(30 ml) was cooled in
(10 ml). The mixture
Cl , and washed
soln. (2×), and sat. NaCl soln. (2×; pH ca. 7). The org. layer was dried
, heptane/Et O 1 :1, then 3 :7 and 1:4) and drying at 0.3 mbar for 2 h
gave 3.10 g (78%) of 11. Pale-yellow oil. R (heptane/Et O 1:4) 0.35. IR (neat): 2871m, 2820m, 1711s, 1650w,
644w, 1628w, 1606m, 1566w, 1537w, 1506w, 1452m, 1402m, 1363w, 1351m, 1333w, 1310w, 1269s, 1027m,
2
Cl
2
was stirred at r.t. for 2 d. The formed precipitate was filtered off and the filtrate taken up in CH
with 10% HCl soln. (2×), sat. Na CO
Na SO ) and evaporated. CC (SiO
2
2
2
3
(
2
4
2
2
f
2
1
1
1
3
015m, 989m, 918m, 859m, 781m, 713m, 668w. H-NMR (400 MHz, CDCl ): 8.01 (d, J=8.2, 2 H); 7.45 (d,
J=8.7, 2 H); 6.75 (dd, J=10.8, 17.7, 1 H); 5.86 (d, J=16.9, 1 H); 5.38 (d, J=10.8, 1 H); 4.51–4.44 (m, 2 H);
1
3
3
.87–3.80 (m, 2 H); 3.75–3.69 (m, 2 H); 3.69–3.61 (m, 4 H); 3.55–3.50 (m, 2 H); 3.36 (s, 3 H). C-NMR
(
100.6 MHz, CDCl ): 166.27 (s); 141.98 (s); 136.02 (d); 130.00 (d); 129.25 (s); 126.07 (d); 116.49 (t); 71.92 (t);
3
70.72 (t); 70.64 (t); 70.59 (t); 69.24 (t); 64.11 (t); 59.01 (q). EI-MS: 262 (4), 218 (3), 176 (8), 175 (63), 174 (5),
149 (4), 148 (13), 132 (11), 131 (100), 104 (3), 103 (26), 102 (8), 101 (3), 89 (7), 88 (3), 87 (7), 77 (16), 59 (24),
58 (15), 45 (7).
(
ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methylprop-2-enoate (2). A descri-
bed for 11, with freshly distilled 8 (2.87 g, 33.3 mmol), DMAP (3.25 g, 26.6 mmol), 12 (7.00 g, 33.3 mmol),
CH Cl (35 ml), and DCC (7.54 g, 36.6 mmol) in CH Cl (15 ml; addition within 20 min) for 5 d. Repetitive
CC (SiO , heptane/Et O 9 :1) gave 4.67 g (63%) of 2. Pale yellow oil. R (heptane/Et O 9 :1) 0.26. IR (neat):
017w, 2956m, 2929m, 2872m, 2829w, 1709s, 1652w, 1636m, 1451m, 1399m, 1375s, 1352m, 1317s, 1296s, 1266w,
250w, 1225w, 1211w, 1164s, 1136s, 1115m, 1077m, 1062m, 1030s, 1008m, 998m, 987w, 937s, 911m, 900w, 885w,
2
2
2
2
2
2
f
2
3
1
8
2
1
62m, 848m, 813m, 787m, 752m, 699s, 682s. H-NMR (400 MHz, CDCl
3
): 6.06–6.02 (m, 1 H); 5.58–5.49 (m,
H); 5.48–5.35 (m, 2 H); 3.05, 2.89 (dd, J=17.9, 6.7, 1 H); 2.71, 2.54 (dd, J=17.9, 6.1, 1 H); 2.58–2.46 (m, 1
H); 2.29–2.21 (m, 1 H); 2.02–1.93 (m, 1 H); 1.92 (m, 3 H); 1.75–1.66 (m, 1 H); 1.32 (2d, J=6.1, 3 H); 1.02,
1
3
0
.99 (2s, 3 H); 0.95, 0.93 (2s, 3 H); 0.89, 0.88 (2d, J=7.2, 6.7, 3 H). C-NMR (100.6 MHz, CDCl
3
): 211.50 (s);
2
11.20 (s); 166.55 (s); 136.63 (s); 136.60 (s); 131.80 (d); 131.73 (d); 125.15 (t); 125.10 (t); 124.19 (d); 124.13
(d); 67.03 (d); 66.79 (d); 63.04 (d); 62.87 (d); 53.21 (t); 41.75 (t); 41.71 (t); 33.12 (s); 33.09 (s); 31.63 (d);
31.53 (d); 29.75 (q); 20.69 (q); 19.96 (q); 19.93 (q); 19.84 (q); 18.34 (q); 18.31 (q). EI-MS: 193 (6), 192 (40),
177 (7), 155 (5), 149 (3), 135 (5), 124 (5), 123 (34), 122 (24), 121 (5), 109 (4), 108 (8), 107 (31), 95 (5), 93 (5),
91 (7), 87 (3), 83 (5), 82 (3), 81 (17), 79 (6), 77 (4), 70 (5), 69 (100), 67 (6), 55 (5), 53 (3), 43 (7), 42 (3), 41
(
21), 39 (6).
ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 4-Ethenylbenzoate (3). As described
for 11, with 10 (2.35 g, 15.9 mmol), DMAP (1.55 g, 12.7 mmol), 12 (4.00 g, 19.1 mmol), CH Cl (30 ml), and
DCC (3.60 g, 17.5 mmol) in CH Cl (10 ml) for 4 d. CC (SiO , heptane/Et O 9 :1) gave 4.02 g (74%) of 2. Color-
less oil. R (heptane/Et O 9 :1) 0.32. UV/VIS (MeCN): 300 (sh, 830), 281 (sh, 15300), 269 (23600), 258 (sh,
6200), 213 (10900). IR (neat): 3017w, 2954m, 2929m, 2870m, 2828w, 1707s, 1651w, 1629w, 1606m, 1566w,
(
2
2
2
2
2
2
f
2
1

3
104
Helvetica Chimica Acta – Vol. 88 (2005)
1
1
507w, 1456m, 1428w, 1402m, 1375m, 1367m, 1354m, 1310m, 1270s, 1226w, 1212w, 1196w, 1177m, 1137m, 1103s,
077w, 1062w, 1044w, 1029m, 1014m, 987m, 962w, 937w, 915m, 885w, 859m, 781m, 712m, 699m, 682m. H-NMR
1
(400 MHz, CDCl
3
): 7.95 (d, J=8.2, 2 H); 7.44 (d, J=8.7, 2 H); 6.74 (dd, J=17.7, 11.0, 1 H); 5.85 (d, J=16.9, 1
H); 5.64–5.49 (m, 2 H); 5.47–5.41 (m, 1 H); 5.37 (d, J=10.2, 1 H); 3.15, 2.79 (2dd, J=17.9, 6.7, 1 H); 3.00, 2.63
(
2dd, J=17.9, 6.1, 1 H); 2.57–2.44 (m, 1 H); 2.27 (t, J=10.0, 1 H); 2.03–1.93 (m, 1 H); 1.75–1.66 (m, 1 H); 1.41
1
3
(
2d, J=6.7, 6.1, 3 H); 1.04, 1.01 (2s, 3 H); 0.95, 0.92 (2s, 3 H); 0.90, 0.88 (2d, J=7.2, 6.7, 3 H). C-NMR (100.6
): 211.49 (s); 211.25 (s); 165.44 (s); 141.81 (s); 136.03 (d); 131.79 (d); 131.71 (d); 129.83 (d); 129.69
s); 129.65 (s); 126.02 (d); 124.20 (d); 124.11 (d); 116.38 (t); 67.41 (d); 67.17 (d); 63.09 (d); 62.90 (d); 53.28 (t);
MHz, CDCl
3
(
4
1.73 (t); 41.69 (t); 33.14 (s); 33.10 (s); 31.61 (d); 31.55 (d); 29.76 (q); 20.69 (q); 20.11 (q); 20.06 (q); 19.87 (q). EI-
MS: 217 (3), 193 (11), 192 (72), 177 (10), 150 (3), 149 (6), 148 (12), 137 (3), 136 (3), 135 (5), 132 (10), 131 (100),
1
8
24 (5), 123 (29), 122 (24), 121 (5), 108 (6), 107 (23), 105 (3), 103 (19), 102 (5), 95 (3), 93 (4), 91 (6), 83 (4), 82 (3),
1 (13), 79 (5), 77 (15), 70 (3), 69 (52), 67 (4), 55 (4), 43 (4), 41 (7).
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methyl-
prop-2-enoate and tert-Butyl 2-Methylprop-2-enoate ca. 1:5 (13a). tert-Butyl 2-methylprop-2-enoate (0.90 g,
6
.3 mmol) and 2 (0.35 g, 1.3 mmol) were dissolved in dry anisole (4 ml) prior to the addition of AIBN (12.4
mg, 0.08 mmol) under N . The mixture was then degassed by means of two freeze-pump-thaw cycles and heated
2
at 908 for 6 h. The polymer was dissolved in THF and precipitated from cold MeOH (twice) to give 0.95 g (76%)
of 13a. White solid. M.p. 151–1778. IR (neat): 2975w, 2933w, 2873w, 2830w, 1717m, 1474w, 1457w, 1391w, 1366m,
1
1
5
1
248m, 1133s, 1029w, 967w, 874w, 846m, 751m, 699w, 682w, 667w. H-NMR (400 MHz, CDCl
3
): 5.53 (m, 1 H);
.45 (m, 1 H); 5.10 (m, 1 H); 3.06 (m, 1 H); 2.86 (m, 1 H); 2.72 (m, 1 H); 2.50 (m, 3 H); 2.36 (m, 1 H); 2.30–
.65 (m, 16 H); 1.42 (m, 45 H); 1.31 (m, 6 H); 1.20–0.74 (m, 25 H). C-NMR (100.6 MHz, CDCl ): 211.32
3
1
3
(
br. s); 177.47 (br. s); 176.66 (br. s); 131.73 (br. d); 124.28 (br. d); 80.91 (br. s); 80.82 (br. s); 67.84 (br. d);
3.05 (br. d); 52.89 (br. t); 46.23 (br. s); 45.34 (br. s); 41.72 (t); 33.05 (br. s); 31.65 (br. d); 29.76 (br. q); 27.81
d); 20.73 (br. q); 19.89 (br. q); 19.62 (br. q); 17.82 (br. q); 17.63 (br. q). Average molecular mass (SEC,
PMMA): M 47000 Da, M 18000 Da.
6
(
w
n
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methyl-
prop-2-enoate and tert-Butyl 2-Methylprop-2-enoate ca. 1 :3 (13b). As described for 13a, with tert-butyl 2-meth-
ylprop-2-enoate (33 ml, 2.0 mmol), 2 (0.19 g, 0.7 mmol), anisole (3.1 ml), and AIBN (4.4 mg, 0.03 mmol): 0.32 g
(
63%) of 13b. White solid. M.p. 96–1058. IR (neat): 2972m, 2931m, 2876m, 2830w, 1718s, 1474m, 1458m, 1390m,
1
1
365s, 1247m, 1133s, 1063m, 1030m, 998w, 968w, 941w, 875w, 846s, 784w, 750m, 699m, 682m. H-NMR (400 MHz,
CDCl ): 5.53 (m, 1 H); 5.46 (m, 1 H); 5.10 (m, 1 H); 3.05 (m, 1 H); 2.86 (m, 1 H); 2.72 (m, 1 H); 2.50 (m, 2 H);
3
1
3
2
.21 (m, 2 H); 2.12–1.63 (m, 8 H); 1.43 (m, 27 H); 1.28 (m, 4 H); 1.20–0.69 (m, 20 H). C-NMR (100.6 MHz,
3
CDCl ): 211.62 (br. s); 176.65 (br. s); 131.79 (br. d); 124.33 (br. d); 80.96 (br. s); 80.61 (br. s); 67.87 (br. d);
6
(
3
2.73 (br. d); 52.88 (br. t); 46.24 (br. s); 45.35 (br. s); 41.70 (t); 33.10 (br. s); 31.68 (br. d); 29.79 (br. q); 27.81
d); 20.71 (br. q); 19.88 (br. q); 19.64 (br. q); 17.91 (br. q). Average molecular mass (SEC, PMMA): M
5800 Da, M 16100 Da.
w
n
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methyl-
prop-2-enoate and tert-Butyl 2-Methylprop-2-enoate ca. 1:2 (13c). As described for 13a, with tert-butyl 2-meth-
ylprop-2-enoate (0.41 ml, 2.5 mmol), 2 (0.35 g, 1.3 mmol), anisole (6 ml), and AIBN (6.2 mg, 0.04 mmol): 0.36 g
(
52%) of 13a. White solid. M.p. 136–1498. IR (neat): 2972m, 2930m, 2874m, 2828w, 1716s, 1653w, 1637w, 1456m,
1
1
390m, 1366s, 1247s, 1133s, 1063m, 1030m, 998w, 969w, 939w, 847s, 751m, 700m, 682m. H-NMR (400 MHz,
CDCl ): 5.53 (m, 1 H); 5.46 (m, 1 H); 5.10 (m, 1 H); 3.05 (m, 1 H); 2.84 (m, 1 H); 2.72 (m, 1 H); 2.50 (m, 2
H); 2.21 (m, 2 H); 2.12–1.63 (m, 6 H); 1.43 (m, 18 H); 1.28 (m, 6 H); 1.20–0.75 (m, 18 H). C-NMR (100.6
MHz, CDCl ): 211.23 (br. s); 177.18 (br. s); 131.70 (br. d); 124.31 (br. d); 81.02 (br. s); 80.58 (br. s); 67.88
br. d); 62.73 (br. d); 52.89 (br. t); 46.23 (br. s); 45.35 (br. s); 41.70 (t); 33.10 (br. s); 31.71 (br. d); 29.77 (br.
q); 27.81 (d); 20.72 (br. q); 19.89 (br. q); 19.66 (br. q); 17.62 (br. q). Average molecular mass (SEC, PMMA):
54100 Da, M 26100 Da.
3
1
3
3
(
M
w
n
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methyl-
prop-2-enoate and tert-Butyl 2-Methylprop-2-enoate ca. 1 :1 (13d). As described for 13a, with tert-butyl 2-meth-
ylprop-2-enoate (0.88 ml, 5.40 mmol), 2 (1.50 g, 5.4 mmol), anisole (20 ml), and AIBN (17.8 mg, 0.11 mmol):
1
.60 g (71%) of 13d. White solid. M.p. 113–1318. IR (neat): 3013w, 2957m, 2932m, 2876w, 2830w, 1714s,
1
654w, 1601w, 1456m, 1391m, 1366s, 1248s, 1133s, 1062w, 1029w, 966w, 941w, 847m, 784w, 751m, 699m, 682m.
1
H-NMR (400 MHz, CDCl
3
): 5.56 (m, 1 H); 5.45 (m, 1 H); 5.10 (m, 1 H); 3.06 (m, 1 H); 2.86 (m, 1 H); 2.72
(
m, 1 H); 2.50 (m, 3 H); 2.21 (m, 2 H); 2.10–1.60 (m, 6 H); 1.42 (m, 9 H); 1.26 (m, 6 H); 1.20–0.80 (m, 12
1
3
3
H). C-NMR (100.6 MHz, CDCl ): 211.29 (br. s); 176.98 (br. s); 131.69 (br. d); 124.30 (br. d); 81.05 (br. s);

Helvetica Chimica Acta – Vol. 88 (2005)
3105
6
7.91 (br. d); 62.72 (br. d); 52.89 (br. t); 46.10 (br. s); 45.36 (br. s); 41.70 (t); 33.10 (br. s); 31.63 (br. d); 29.77 (br.
q); 27.83 (d); 20.76 (br. q); 19.89 (br. q); 19.62 (br. q). Average molecular mass (SEC, PMMA): M 56900 Da,
24600 Da.
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methyl-
prop-2-enoate and 2-Methylprop-2-enoic Acid ca. 1:5 (4a). Trifluoroacetic acid (15 ml) was added to a soln.
of 13a (0.90 g, 0.91 mmol) in CH Cl
(15 ml), and the mixture was stirred at r.t. for 1 h (! orange). Precipitation
into cold Et O then afforded 0.55 g (86%) of 4a. White solid. M.p. 215–2238 (dec.). IR (neat): 3700–2400w (br.),
982m, 2969m, 2956m, 2935m, 2900m, 2838m, 1697s, 1474m, 1449m, 1387m, 1369m, 1252m, 1151s, 1065m, 1029w,
w
M
n
2
2
2
2
9
5
1
99w, 961m, 933m, 832w, 793w, 750w, 700w, 683w, 668w, 632w, 625w, 617w, 605w. H-NMR (400 MHz, MeOD):
.58 (m, 1 H); 5.49 (m, 1 H); 5.11 (m, 1 H); 3.14 (m, 1 H); 2.90 (m, 1 H); 2.67 (m, 1 H); 2.50 (m, 1 H); 2.32 (m, 1
1
3
H); 2.20–1.78 (m, 19 H); 1.75 (m, 2 H); 1.52 (m, 2 H); 1.45 (m, 4 H); 1.30 (m, 7 H); 1.11–0.73 (m, 32 H). C-
NMR (100.6 MHz, MeOD): 213.50 (br. s); 183.69 (br. s); 182.53 (br. s); 182.24 (br. s); 181.34 (br. s); 179.15 (br.
s); 132.81 (br. d); 125.50 (br. d); 69.33 (br. d); 64.03 (br. d); 55.69 (br. t); 54.18 (br. t); 53.20 (br. t); 52.90 (br. t);
4
7.53 (br. s); 46.32 (br. s); 45.94 (br. s); 42.81 (t); 34.19 (br. s); 32.92 (br. d); 30.51 (br. q); 28.24 (br. q); 21.50 (br.
q); 20.33 (br. q); 19.93 (br. q); 19.28 (br. q); 30.51 (br. q); 17.36 (br. q); 17.02 (br. q).
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methyl-
prop-2-enoate and 2-Methylprop-2-enoic Acid ca. 1:3 (4b). As described for 4a, with 13b (0.25 g, 0.4 mmol),
2 2 3
CH Cl (5 ml), and CF COOH (5 ml): 0.12 g (63%) of 4b. White solid. M.p. 235–2468 (dec.). IR (neat):
3
1
696–2182m, 3205m, 3013m, 2977m, 2953m, 2932m, 2881m, 2587m, 1719s, 1694s, 1654m, 1469m, 1449m,
385m, 1368m, 1249m, 1153s, 1030m, 998w, 932m, 832m, 789m, 755m, 700m, 682m. H-NMR (400 MHz,
1
MeOD): 5.58 (m, 1 H); 5.49 (m, 1 H); 5.11 (m, 1 H); 3.14 (m, 1 H); 2.90 (m, 1 H); 2.67 (m, 1 H); 2.50 (m, 1
H); 2.32 (m, 1 H); 2.20–1.78 (m, 10 H); 1.75 (m, 1 H); 1.52 (m, 1 H); 1.30 (m, 5 H); 1.11–0.73 (m, 18 H).
1
3
C-NMR (100.6 MHz, MeOD): 213.70 (br. s); 182.52 (br. s); 182.24 (br. s); 181.34 (br. s); 132.76 (br. d);
25.51 (br. d); 69.33 (br. d); 64.02 (br. d); 55.74 (br. t); 54.12 (br. t); 46.96 (br. q); 46.74 (br. q); 46.33 (br. q);
5.94 (br. q); 42.84 (br. t); 34.16 (br. s); 33.05 (br. d); 32.92 (br. d); 30.53 (br. q); 30.23 (br. q); 21.37 (br. q);
0.36 (br. q); 19.94 (br. q); 19.25 (br. q); 17.99 (br. q); 17.39 (br. q); 17.02 (br. q).
1
4
2
Alternatively, 4b was prepared in one step by adding AIBN (47.4 mg, 0.29 mmol) under N
2
to a soln. of 8
(1.86 g, 21.6 mmol) and 2 (2 g, 7.2 mmol) in dioxane (38 ml). The medium was degassed by means of two freeze-
pump-thaw cycles and then heated at 908 for 4 h. The polymer was precipitated from cold heptane (twice) to
give 2.87 g (74%) of 4b. White solid. Spectral data: as described above.
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethycyclohex-3-en-1-yl)propyl 2-Methylprop-
2
2 2
-enoate and 2-Methylprop-2-enoic Acid ca. 1 :2 (4c). As described for 4a, with 13c (0.30 g, 0.5 mmol), CH Cl (5
3
ml), and CF COOH (5 ml): 0.17 g (71%) of 4c. White solid. M.p. 223–2368 (dec.). IR (neat): 3701–2324s (br.),
2
7
954s, 2932s, 2872s, 2830m, 1717s, 1696s, 1452s, 1368s, 1248s, 1136s, 1065s, 1031s, 998m, 963s, 935s, 834s, 792s, 755s,
00s, 682s. H-NMR (400 MHz, MeOD): 5.58 (m, 1 H); 5.49 (m, 1 H); 5.11 (m, 1 H); 3.16 (m, 1 H); 2.90 (m, 1
1
H); 2.66 (m, 1 H); 2.50 (m, 1 H); 2.33 (m, 1 H); 2.26–1.80 (m, 7 H); 1.74 (m, 1 H); 1.46 (m, 1 H); 1.30 (m, 4 H);
1
3
1
1
.12–0.86 (m, 15 H). C-NMR (100.6 MHz, MeOD): 182.20 (br. s); 181.27 (br. s); 169.39 (br. s); 132.76 (br. d);
25.51 (br. d); 69.28 (br. d); 64.03 (br. d); 63.89 (br. d); 55.68 (br. t); 54.08 (br. t); 46.72 (br. s); 46.31 (br. s); 45.92
(
1
br. s); 42.83 (br. t); 34.17 (br. s); 33.08 (br. d); 32.91 (br. d); 30.53 (br. q); 21.49 (br. q); 20.56 (br. q); 20.40 (br. q);
9.97 (br. q).
Alternatively, 4c was also prepared in one step as described for 4b, with 2 (2.00 g, 7.2 mmol), 8 (1.24 g, 14.4
mmol), and dioxane (36 ml): 2.55 g (79%) of 4c. White solid. Spectral data: as described above.
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methyl-
prop-2-enoate and 2-Methylprop-2-enoic Acid ca. 1:1 (4d). As described for 4a, with 13d (0.15 g, 0.4 mmol),
2 2 3
CH Cl (5 ml), and CF COOH (5 ml): 0.10 g (77%) of 4d. White solid. M.p. 221–2268 (dec.). IR (neat):
3
1
666–2385m (br.), 3013m, 2956s, 2932s, 2876s, 2830m, 1722s, 1700s, 1654m, 1459m, 1448m, 1374s, 1248s,
135s, 1062s, 1029s, 936s, 840m, 789m, 749m, 700m, 682m. H-NMR (400 MHz, MeOD): 5.60 (m, 1 H); 5.51
1
(
m, 1 H); 5.11 (m, 1 H); 3.15 (m, 1 H); 2.90 (m, 1 H); 2.77 (m, 1 H); 2.51 (m, 2 H); 2.34 (m, 2 H); 2.26–1.63
1
3
(m, 8 H); 1.31 (m, 4 H); 1.23–0.77 (m, 9 H). C-NMR (100.6 MHz, MeOD): 213.42 (br. s); 185.10 (br. s);
81.69 (br. s); 174.45 (br. s); 132.78 (br. d); 125.55 (br. d); 69.40 (br. d); 64.00 (br. d); 54.06 (br. t); 46.49 (br.
1
s); 46.34 (br. s); 45.91 (br. s); 42.81 (br. t); 34.21 (br. s); 32.98 (br. t); 30.54 (br. q); 21.57 (br. q); 20.44 (br.
q); 20.06 (br. q); 17.33 (br. q); 17.09 (br. q).
Alternatively, 4d was also prepared in one step as described for 4b, with 2 (2.00 g, 7.2 mmol), 8 (0.62 g, 7.2
mmol), and dioxane (30 ml): 1.95 g (74%) of 4d. White solid. Spectral data: as described above.
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 2-Methyl-
prop-2-enoate and 2-(2-Methoxyethoxy)ethyl 2-Methylprop-2-enoate ca. 1 :2 (5d). A stirred soln. of 2 (0.15 g,

3
106
Helvetica Chimica Acta – Vol. 88 (2005)
0.54 mmol) and 2-(2-methoxyethoxy)ethyl 2-methylprop-2-enoate (9; 0.10 g, 0.53 mmol) in dry THF (3 ml) was
degassed with Ar for a few minutes. Then AIBN (3.0 mg, 0.02 mmol) was added, and the mixture was heated at
08 for 15 h. After cooling to r.t., CH Cl (1 ml) was added and the mixture slowly poured into hexane (30 ml) to
precipitate 0.23 g (94%) of 5d. White solid. IR (neat): 3015w, 2954m, 2927m, 2875m, 2828m, 1721s, 1650m,
5
2
2
1
8
522w, 1453m, 1373m, 1366m, 1327w, 1290m, 1247m, 1131s, 1108s, 1063m, 1028s, 998m, 984m, 965m, 940m,
98w, 860m, 851m, 806w, 797w, 787m, 772w, 748m, 699m, 682m, 656w. H-NMR (400 MHz, (D )THF): 5.53
8
1
(
3
(
m, 1 H); 5.46 (m, 1 H); 5.09 (m, 1 H); 4.07 (m, 2 H); 3.66 (m, 2 H); 3.60 (m, 2 H); 3.52 (m, 2 H); 3.33 (br. s,
1
3
H); 3.22–2.40 (m, 3 H); 2.28 (m, 1 H); 2.20–1.60 (m, 9 H); 1.28 (br. s, 3 H); 1.20–0.70 (m, 12 H). C-NMR
)THF): 211.42 (s); 177.74 (s); 177.14 (s); 132.74 (d); 132.61 (d); 125.09 (br. d); 72.94 (t);
100.6 MHz, (D
8
7
4
1.26 (t); 69.37 (t); 68.43 (br. d); 64.73 (t); 63.36 (br. d); 59.11 (q); 55.17 (br. t); 53.69 (t); 45.98 (s); 45.64 (s);
2.51 (t); 33.73 (d); 32.55 (q); 30.24 (q); 30.01 (q); 21.12 (q); 20.36 (q); 20.16 (q); 19.95 (q); 17.92 (br. q). Average
molecular mass (SEC, narrow standard calibration, PMMA): ca. 51100 Da.
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 4-Ethenyl-
benzoate and 4-Ethenylbenzoic Acid ca. 1:5 (6a). A soln. of 3 (1.00 g, 2.9 mmol), 10 (1.30 g, 8.8 mmol, 3
equiv.), and AIBN (0.10 g, 0.6 mmol) in dry THF (20 ml) was heated under N
2
at 808 for 2 d. More AIBN
(0.10 g) was added and, after another 2 d, the mixture was concentrated and the crude product redissolved in
THF (3 ml) and then precipitated with heptane (4 ml, 3×). Drying at 0.3 mbar afforded 1.93 g (62%) of a
white solid still containing some impurities. NMR integrations revealed an average ratio of the two monomers
of ca. 1:5 in the final polymer 6a. M.p. 308–3188 (dec.). IR (neat): 2925m (br.), 2870w, 2644w (br.), 2537w (br.),
1
8
5
685s, 1606s, 1573m, 1508w, 1448w, 1419m, 1368m, 1311m, 1271s (br.), 1176s, 1101m, 1046m, 1016m, 936w, 882w,
1
54m, 800m, 774s, 705s, 684w, 670w. H-NMR (400 MHz, (D
8
)THF): 8.10–7.40 (m, 12 H); 7.20–6.30 (m, 12 H);
.62–5.38 (m, 3 H); 3.34–2.98 (m, 1 H); 2.98–2.62 (m, 1 H); 2.57–2.41 (m, 1 H); 2.41–2.26 (m, 1 H); 2.26–1.18
1
3
(
m, 23 H); 1.18–0.68 (m, 9 H). C-NMR (100.6 MHz, (D
50.58 (br. s); 132.67 (d); 130.58 (br. d); 129.81 (br. s); 128.39 (br. d); 125.06 (d); 124.85 (d); 63.28 (d); 54.03
t); 44.46 (br. t); 42.50 (t); 41.65 (br. d); 33.69 (s); 32.56 (d); 30.04 (q); 21.08 (q); 20.16 (br. q). Average molecular
mass (SEC, PS): M 2100 Da, M 1600 Da.
8
)THF): 211.64 (br. s); 167.59 (br. s); 165.65 (br. s);
1
(
w
n
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 4-Ethenyl-
benzoate and 2-[2-(2-Methoxyethoxy)ethoxy]ethyl 4-Ethenylbenzoate ca. 1 :3 (7b). A soln. of 3 (0.19 g, 0.57
mmol) and 11 (0.50 g, 1.7 mmol, 3 equiv.) in dry THF (5 ml) was rapidly added to a stirred soln. of AIBN
2
(0.05 g, 0.3 mmol) in dry THF (5 ml) under N . The mixture was heated at 808 for 90 h. After cooling to r.t.,
MeOH (1 ml) was added and the mixture concentrated. The crude product was taken up into THF (2 ml)
and extracted with heptane (4–6 ml). The heptane phase was decanted and the procedure repeated twice
(with 1.5 ml of THF and 3 ml of heptane). Evaporation of the heptane phases and drying at 0.3 mbar for 2 h
afforded 0.39 g (56%) of 7b. Highly viscous oil. IR (neat): 2927m, 2869m, 1711s, 1650w, 1607m, 1573w,
1
9
5
507w, 1451m, 1418m, 1373m, 1366m, 1352m, 1307m, 1270s, 1197m, 1179m, 1098s, 1029m, 1016m, 998w, 985w,
1
40m, 853m, 772m, 707m, 683m. H-NMR (400 MHz, CDCl
3
): 8.10–7.40 (m, 8 H); 7.00–6.20 (m, 8 H); 5.61–
.39 (m, 3 H); 4.55–4.33 (m, 6 H); 3.93–3.78 (m, 6 H); 3.78–3.60 (m, 18 H); 3.59–3.47 (m, 6 H); 3.41–3.32
(
m, 9 H); 3.25–2.94 (m, 1 H); 2.92–2.59 (m, 1 H); 2.58–2.44 (m, 1 H); 2.38–2.22 (m, 1 H); 2.08–1.20 (m, 17
1
3
H); 1.18–0.75 (m, 9 H). C-NMR (100.6 MHz, CDCl
1
5
3
): 166.12 (s); 165.32 (s); 149.31 (br. s); 131.73 (d);
29.59 (br. d); 128.23 (br. d); 124.28 (d); 71.93 (t); 70.64 (t); 70.57 (t); 69.19 (t); 67.97 (t); 64.02 (t); 62.88 (d);
9.03 (q); 53.28 (t); 41.72 (t); 40.66 (br. d); 33.11 (s); 21.63 (d); 29.77 (q); 20.73 (q); 20.10 (q); 19.89 (q). Average
12100 Da, M 7700 Da.
molecular mass (SEC, PS): M
w
n
Random Copolymer of (ꢀ)-1-Methyl-3-oxo-3-(trans-2,6,6-trimethylcyclohex-3-en-1-yl)propyl 4-Ethenyl-
benzoate and 2-[2-(2-Methoxyethoxy)ethoxy]ethyl 4-Ethenylbenzoate ca. 1:2 (7c). As described for 7b, with 3
(0.29 g, 0.85 mmol) and 11 (0.50 g, 1.7 mmol, 2 equiv.): 0.53 g (67%) of 7c. Highly viscous oil. IR (neat):
3
1
013w, 2922m, 2870m, 1710s, 1651w, 1607m, 1573w, 1507w, 1451m, 1418m, 1374m, 1365m, 1352m, 1307m,
270s, 1197m, 1179m, 1135m, 1098s, 1029m, 1016m, 999w, 986w, 940m, 826w, 852m, 771m, 707s, 682m. H-
1
NMR (400 MHz, CDCl
3
): 8.10–7.30 (m, 6 H); 6.90–6.20 (m, 6 H); 5.61–5.39 (m, 3 H); 4.55–4.34 (m, 4 H);
3
2
.93–3.77 (m, 4 H); 3.77–3.60 (m, 12 H); 3.59–3.47 (m, 4 H); 3.41–3.32 (m, 6 H); 3.26–2.94 (m, 1 H); 2.92–
1
3
.59 (m, 1 H); 2.57–2.44 (m, 1 H); 2.38–2.22 (m, 1 H); 2.07–1.18 (m, 14 H); 1.16–0.75 (m, 9 H). C-NMR
): 211.72 (br. s); 166.13 (s); 165.31 (s); 149.15 (br. s); 131.74 (d); 129.56 (br. d); 128.57 (br.
d); 128.10 (br. d); 127.40 (br. d); 124.28 (d); 124.15 (d); 71.93 (t); 70.64 (t); 70.57 (t); 69.18 (t); 67.29 (br. d);
3.98 (t); 62.88 (d); 59.03 (q); 53.28 (t); 41.72 (t); 40.67 (br. d); 33.11 (s); 31.63 (d); 29.78 (q); 20.74 (q); 20.10
q); 19.89 (q). Average molecular mass (SEC, PS): M 14700 Da, M 8200 Da.
Extraction Experiments in the Presence of Surfactant. Buffer solns. containing 1% by weight of surfactant
were prepared by dissolving (under sonication) two buffer tablets pH 4.0 (phthalate; Fluka) or two buffer tab-
(
100.6 MHz, CDCl
3
6
(
w
n

Helvetica Chimica Acta – Vol. 88 (2005)
3107
®
lets pH 9.2 (borate; Fluka) and 2.24 g of Triton X100 (Union Carbide) or SDS (Sigma) in a mixture of H
2
O (160
ml) and MeCN (40 ml; 31.3 g) (4 :1). To determine the exact pH of the final reaction solns., 10 ml of the buffers
were diluted with 2 ml of MeCN (to give a mixture of H O/MeCN 2 :1), and the pH was measured (Mettler-Tol-
2
edo-MP220 apparatus with an InLab-410 Ag/AgCl glass electrode) at 208 to be 4.97ꢀ0.04 and 10.48ꢀ0.03 in the
®
case of Triton X100, and 10.16ꢀ0.01 in the case of SDS. To 5 ml of the acidic or alkaline buffer solns. (H
2
O/
MeCN 4 :1) were added 50 ml of a ca. 0.25
of monomers 2, 3, and 14, copolymers 4–7, or d-damascone in THF, and the solns. were diluted with 1 ml of
MeCN to give a final mixture H O/MeCN 2 :1. The samples were stirred at r.t. for 3 d, then extracted with 1
ml of heptane and left decanting for 30 min. The heptane extracts (0.5 ml) were subjected in triplicate to GC
M soln. (corresponding to the amount of damascone in the molecule)
2
(
(
Carlo-Erba-MFC-500 gas chromatograph; Fisons-AS-800 autosampler; J&W Scientific-DB1 capillary column
30 m, 0.32 mm i.d.) at 708 for 10 min then to 2608 (108/min), or at 1008 to 2208 (108/min); helium pressure 50
kPa; inj. temp. 250–2608, det. temp. 240–2808). The amount of d-damascone (1) was determined by exter-
nal-standard calibration from five or six different concentrations in heptane, by using an average of five injec-
tions for each calibration point.
Fluorescence Probing Experiments. Fluorescence emission spectra of pyrene solubilized in copolymer solns.
were recorded in the range of 360–460 nm at an excitation wavelength of 334.5 nm and pyrene concentrations
sufficiently low to ensure the absence of excimers. According to the molecular mass of their repeat unit, 20–60
®
mg of random copolymers 4 or 6 were dispersed in 38 ml of a buffer soln. (CertiPUR from Merck) at pH 4, 7,
ꢁ
5
and 9, resp., and 2 ml of a 10
damascone, 5·10
M
pyrene soln. in EtOH was added. The final soln. thus contained 0.0209 m
M of d-
ꢁ
7
M pyrene, and a total of 5% of EtOH. Each soln. was divided into four samples of 10 ml, three
of which were pipetted into 10-ml flasks (to have no free headspace above the sample solns.). The flasks were
closed and the solns. stirred at r.t. (constant at ca. 238) for 24, 48, and 72 h, resp. The remaining 10 ml were ana-
lyzed immediately after preparation (after ca. 1–2 h). For the analysis, the samples were split, 2 ml were taken
for the fluorescence measurements, 2 ml for the measurements of the particle sizes (1 ml of each soln. was ana-
lyzed in a DTS-1060 folded capillary cell from Malvern), and the remaining 6 ml were extracted with 1 ml of
heptane. The damascone content in the heptane phase was analyzed by GC as described above.
We thank Maude Gaillard, Laurence Frascotti, Géraldine León, and José Galindo for their contributions to
this project, as well as Dr. Roger Snowden for constructive comments on the manuscript.
REFERENCES
[1] S.-J. Park, R. Arshady, Microspheres, Microcapsules, Liposomes 2003, 6, 157; J. Ness, O. Simonsen, K.
Symes, Microspheres, Microcapsules, Liposomes 2003, 6, 199; L. Brannon-Peppas, ACS Symp. Ser. 1993,
520, 42 and refs. cited in these reports.
[
[
[
2] M. Gautschi, J. A. Bajgrowicz, P. Kraft, Chimia 2001, 55, 379.
3] H. Kamogawa, H. Mukai, Y. Nakajima, M. Nanasawa, J. Polym. Sci., Polym. Chem. Ed. 1982, 20, 3121.
4] H. Kamogawa, S. Okabe, M. Nanasawa, Bull. Chem. Soc. Jpn. 1976, 49, 1917; H. Kamogawa, Y. Haramoto,
M. Nanasawa, Bull. Chem. Soc. Jpn. 1979, 52, 846; O. Galioglu, A. Akar, J. Polym. Sci. Part A: Polym.
Chem. 1988, 26, 2355; H. Kamogawa, H. Kohno, R. Kitagawa, J. Polym. Sci. Part A: Polym. Chem.
1989, 27, 487; V. Athawale, N. Manjrekar, M. Athawale, Tetrahedron Lett. 2002, 43, 4797.
[5] E. Frérot, K. Herbal, A. Herrmann, Eur. J. Org. Chem. 2003, 967.
[
6] P. Enggist, S. Rochat, A. Herrmann, J. Chem. Soc., Perkin Trans. 2 2001, 438; J.-Y. de Saint Laumer, E.
Frérot, A. Herrmann, Helv. Chim. Acta 2003, 86, 2871.
[
[
[
7] Y. Yang, D. Wahler, J.-L. Reymond, Helv. Chim. Acta 2003, 86, 2928.
8] A. Herrmann, The Spectrum (Bowling Green) 2004, 17 (2), 10–13 and 19.
9] S. Rochat, C. Minardi, J.-Y. de Saint Laumer, A. Herrmann, Helv. Chim. Acta 2000, 83, 1645; A. Herrmann,
C. Debonneville, V. Laubscher, L. Aymard, Flavour Fragr. J. 2000, 15, 415; C. Plessis, S. Derrer, Tetrahe-
dron Lett. 2001, 42, 6519; B. Levrand, A. Herrmann, Photochem. Photobiol. Sci. 2002, 1, 907; J. Pika, A.
Konosonoks, R. M. Robinson, P. N. D. Singh, A. D. Gudmundsdottir, J. Org. Chem. 2003, 68, 1964; J.
Lage Robles, C. G. Bochet, Org. Lett. 2005, 7, 3545.
[10] T. Ikemoto, B.-I. Okabe, K. Mimura, T. Kitahara, Flavour Fragr. J. 2002, 17, 452; T. Ikemoto, K. Mimura, T.
Kitahara, Flavour Fragr. J. 2003, 18, 45.
[
[
[
11] D. Kastner, Parfuem. Kosmet. 1994, 75(3), 170; A. Williams, Perfum. Flavor. 2002, 27(2), 18.
12] C. Fehr, J. Galindo, Helv. Chim. Acta 2005, 88, 3128.
13] E. D. Bergmann, D. Ginsburg, R. Pappo, Org. React. 1959, 10, 179.

3
108
Helvetica Chimica Acta – Vol. 88 (2005)
[
14] J.-L. P. Bettiol, A. Busch, H. Denutte, C. Laudamiel, P. M. K. Perneel, M. M. Sanchez-Pena, J. Smets, to
The Procter&Gamble Company, PCT Int. Patent Appl. WO 00/02991, 2000; A. Busch, M. Homble, C. Lau-
damiel, J. Smets, R. Trujillo, J. Wevers, to The Procter&Gamble Company, Eur. Patent Appl. EP 0 971 021,
2000 (Chem. Abstr. 2000, 132, 80090).
[15] C. Fehr, A. Struillou, J. Galindo, to Firmenich SA, PCT Int. Patent Appl. WO 03/049666, 2003 (Chem.
Abstr. 2003, 139, 41490); C. Fehr, A. Struillou, J. Galindo, to Firmenich SA, PCT Int. Patent Appl. WO
0
4/105713, 2004 (Chem. Abstr. 2005, 142, 43503).
16] A. Herrmann, E. Frérot, to Firmenich SA, PCT Int. Patent Appl. WO 02/077074, 2002 (Chem. Abstr. 2002,
37, 284012).
17] R. Langer, Nature (London) 1998, 392 Suppl., 5; K. E. Uhrich, S. M. Cannizzaro, R. S. Langer, K. M.
Shakesheff, Chem. Rev. 1999, 99, 3181; C. Alexander, Expert Opin. Emerging Drugs 2001, 6, 345; R. Dun-
can, Nat. Rev. Drug Disc. 2003, 2, 347; K. Hoste, K. De Winne, E. Schacht, Int. J. Pharm. 2004, 277, 119; A.
J. M. D’Souza, E. M. Topp, J. Pharm. Sci. 2004, 93, 1962.
[
[
1
[
18] P. Alexandridis, Curr. Opin. Colloid Interface Sci. 1996, 1, 490; W. Meier, Chem. Soc. Rev. 2000, 29, 295; S.
Kimura, T. Kidchob, Y. Imanishi, Polym. Adv. Technol. 2001, 12, 85; A. Rösler, G. W. M. Vandermeulen,
H.-A. Klok, Adv. Drug Delivery Rev. 2001, 53, 95; G. Riess, P. Dumas, G. Hurtrez, Microspheres, Micro-
capsules, Liposomes 2002, 5, 60; M. L. Adams, A. Lavasanifar, G. S. Kwon, J. Pharm. Sci. 2003, 92,
1343; G. S. Kwon, Crit. Rev. Ther. Drug Carrier Syst. 2003, 20, 357; C. de las Heras Alarcón, S. Pennadam,
C. Alexander, Chem. Soc. Rev. 2005, 34, 276.
[
[
19] K. Nakashima, Y. Fujimoto, T. Anzai, H. Sato, Y. Ozaki, Bull. Chem. Soc. Jpn. 1999, 72, 1233 and refs. cited
therein.
20] B. D. Mookherjee, R. W. Trenkle, R. A. Wilson, F. L. Schmitt, M. H. Vock, E. J. Granda, to International
Flavors and Fragrances Inc., Ger. Offen. DE 28 40 823, 1979 (Chem. Abstr. 1979, 91, 162898); B. D. Moo-
kherjee, R. W. Trenkle, R. A. Wilson, F. L. Schmitt, M. H. Vock, E. J. Granda, to International Flavors and
Fragrances Inc., Fr. Demande FR 2 422 616, 1979 (Chem. Abstr. 1980, 92, 163623).
21] K. Matyjaszewski, T. P. Davis, ‘Handbook of Radical Polymerization’, John Wiley & Sons, Hoboken, 2002;
G. Moad, D. H. Solomon, ‘The Chemistry of Free Radical Polymerization’, Elsevier Science, Oxford, 1995;
[
‘
Comprehensive Polymer Science: The Synthesis, Characterization, Reactions and Applications of Poly-
mers’, Vol. 3, Eds. G. Allen, J. C. Bevington, G. C. Eastmond, A. Ledwith, S. Russo, and P. Sigwalt, Perga-
mon Press, Oxford, 1989.
[
[
[
22] S. Ludwigs, K. Schmidt, G. Krausch, Macromolecules 2005, 38, 2376.
23] S. Liu, S. P. Armes, Langmuir 2003, 19, 4432.
24] G. B. Bachman, C. L. Carlson, M. Robinson, J. Am. Chem. Soc. 1951, 73, 1964; J. R. Leebrick, H. E. Rams-
den, J. Org. Chem. 1958, 23, 935; J. Cazes, J. Tréfouël, C. R. Hebd. Séances Acad. Sci. 1958, 247, 1874; J. H.
Cameron, S. Graham, J. Chem. Soc., Dalton Trans. 1989, 1599.
[
[
[
[
25] B. Neises, W. Steglich, Org. Synth., Coll. Vol. VII 1990, 93.
26] H. Mori, A. H. E. Müller, Prog. Polym. Sci. 2003, 28, 1403.
27] K. Kalyanasundaram, J. K. Thomas, J. Am. Chem. Soc. 1977, 99, 2039.
28] J. K. Thomas, Chem. Rev. 1980, 80, 283; G. R. Ramos, M. C. G. Alvarez-Coque, A. Berthod, J. D. Wine-
fordner, Anal. Chim. Acta 1988, 208, 1; B. Valeur, Chem. Anal. (N. Y.) 1993, 77, 25; F. M. Winnik,
Chem. Rev. 1993, 93, 587; G. Duportail, P. Lianos, Surfactant Sci. Ser. 1996, 62, 295; P. Bosch, F. Catalina,
T. Corrales, C. Peinado, Chem.–Eur. J. 2005, 11, 4314.
[
[
[
29] ‘Surfactant Solutions. New Methods of Investigation’, Surfactant Science Series, Vol. 22, Ed. R. Zana, Mar-
cel Dekker Inc., New York, 1987; ‘Applied Fluorescence in Chemistry, Biology and Medicine’, Eds. W.
Rettig, B. Strehmel, S. Schrader, and H. Seifert, Springer, Berlin, 1999.
30] W. Binana-Limbele, R. Zana, Macromolecules 1987, 20, 1331; M.-A. Yessine, M. Lafleur, C. Meier, H.-U.
Petereit, J.-C. Leroux, Biochim. Biophys. Acta 2003, 1613, 28; M. Pinteala, V. Epure, V. Harabagiu, B. C.
Simionescu, S. Schlick, Macromolecules 2004, 37, 4623.
31] D. F. Anghel, J. L. Toca-Herrera, F. M. Winnik, W. Rettig, R. von Klitzing, Langmuir 2002, 18, 5600.
Received August 12, 2005