Vanillin, a promising biobased building-block for monomer synthesis

Article abstract of DOI:10.1039/c3gc42613k

Vanillin was used as a renewable building-block to develop a platform of 22 biobased compounds for polymer chemistry. Vanillin-derived biobased monomers bearing epoxy, cyclic carbonates, allyl, amine, alcohol and carboxylic acid moieties were synthesized. They can be used, among many others, in epoxy, polyester, polyurethanes, and Non-Isocyanate PolyUrethanes (NIPU) polymer synthesis. The epoxy-functionalized compounds were synthesized under solvent-free conditions and are original biobased aromatic epoxy monomers. Cyclic carbonates were prepared through a catalytic reaction between epoxy compounds and CO₂. Thiol-ene reactions allowed the functionalization of allylated compounds with amines, acids and alcohols. The amine-functionalized compounds are, to our knowledge, the first non-aliphatic biobased amine hardeners, usable either in epoxy or NIPU materials. the Partner Organisations 2014.

Full text of DOI:10.1039/c3gc42613k

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Vanillin, a promising biobased building-block for
monomer synthesis
Cite this: Green Chem., 2014, 16,
1987
Maxence Fache,a Emilie Darroman,a Vincent Besse,b Rémi Auvergne,a
Sylvain Caillol*a and Bernard Boutevina
Vanillin was used as a renewable building-block to develop a platform of 22 biobased compounds for
polymer chemistry. Vanillin-derived biobased monomers bearing epoxy, cyclic carbonates, allyl, amine,
alcohol and carboxylic acid moieties were synthesized. They can be used, among many others, in epoxy,
polyester, polyurethanes, and Non-Isocyanate PolyUrethanes (NIPU) polymer synthesis. The epoxy-func-
tionalized compounds were synthesized under solvent-free conditions and are original biobased aromatic
epoxy monomers. Cyclic carbonates were prepared through a catalytic reaction between epoxy com-
pounds and CO2. Thiol–ene reactions allowed the functionalization of allylated compounds with amines,
acids and alcohols. The amine-functionalized compounds are, to our knowledge, the first non-aliphatic
biobased amine hardeners, usable either in epoxy or NIPU materials.
Received 23rd December 2013,
Accepted 18th February 2014
DOI: 10.1039/c3gc42613k
www.rsc.org/greenchem
based on cardanol6 or natural flavonoids7,8 to synthesize
promising materials, lignin is the most abundant feedstock.9
Introduction
Recent years have witnessed an increasing demand for renew- Lignin is an amorphous cross-linked polymer that gives struc-
able resource-derived polymers (biobased polymers) owing to tural integrity to plants, making up 25 to 35% of woody
increasing environmental concerns and restricted availability biomass.10 Thus, depolymerization of lignin is an alluring
of petrochemical resources.1,2 Some solutions are already route to gain access to biobased aromatics needed by the
industrially available but most of these biobased polymers are chemical industry. Unfortunately, this route is deceptive.
aliphatic or cycloaliphatic polymers, for instance derived from Despite extensive research,11 there are very few reports on
cellulose,1 starch1 or triglycerides.3 However, many key com- efficient ways of recovering such aromatic products.
mercial chemicals are aromatic compounds, ultimately derived
from petrochemical feedstocks.2
The only notable commercial process has been the histori-
cal production of vanillin from lignosulfonates contained in
More recently, great attention was paid to renewable the “brown liquor”, a by-product of the sulfite pulping paper
resources-derived thermosetting materials,4 especially because industry. Even though this process uses cheap and available
they are crosslinked polymers and thus cannot be recycled. waste materials, its use declined because of environmental
Also, most of the thermosetting materials contain aromatic concerns. Nowadays, Solvay dominates the vanillin market
monomers, able to confer high mechanical and thermal pro- using the petroleum-based catechol–guaiacol process. 85% of
perties to the network. Moreover, some base chemicals used the vanillin is produced by this method and 15% still from
nowadays have proven harmful and need to be replaced. For lignin.12,13
instance, bisphenol A is extensively used for the manufactur-
Most recently, however, lignin-to-vanillin routes regained a
ing of epoxy resins even though it is a reprotoxic substance.5 lot of interest12–14 with technical advances in processes15 as
Therefore, access to biobased and non-harmful aromatic well as waste management. For instance, Borregaard, the
monomers is one of the main challenges of the years to second largest vanillin producer in the world and the only one
come.
with a vanillin-from-lignin process, employs an ultrafiltration
The three main sources of renewable aromatic compounds technology, achieving a reduction in waste stream volumes.16
available are cashew nutshell liquid, polyphenols and lignin. Therefore, instead of expecting various biobased aromatics
Even though there have been some very interesting studies from lignin depolymerization, which is not a mature technol-
ogy, the improvement of lignin-to-vanillin processes and the
use of vanillin as a biobased building-block for polymer chem-
aInstitut Charles Gerhardt, UMR CNRS 5253, Equipe Ingénierie et Architectures
istry seem a better perspective.
Macromoléculaires, ENSCM, 8 rue de l’Ecole Normale, 34296 Montpellier, France.
Even though the lignin-derived vanillin is becoming rela-
tively easily accessible, still there are only a handful of reports
E-mail: sylvain.caillol@enscm.fr
bCOLAS S.A., 7 place René Clair, 92653 Boulogne-Billancourt, France
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on attempts to utilize vanillin as monomers for biobased synthesized directly from vanillin, sorbitol, and pyrogallol with
polymer synthesis. Amarasekara et al. have reported the dimeri- wood flour.30
zation and electrochemical reductive polymerization with
From the few but interesting studies cited, it is clear that
horseradish peroxidase.17 The Schiff base synthesized was vanillin has a huge potential to meet the aforementioned chal-
used for metal ion chelation applications.18 Schiff bases from lenge concerning biobased monomers. It is biobased, poten-
vanillin were also prepared by Issam et al. and transformed tially abundantly available and does not compete with edible
into epoxies in a second step.19 Concerning epoxy compounds, resources. Its aromatic structure could provide the desired
Aouf et al. prepared the allylated vanillic acid and worked on thermal and mechanical properties to materials and its
its epoxidation by a chemo-enzymatic process with Candida different substituents led us to consider it to be a versatile bio-
antarctica lipase.20 Koike described an interesting process based platform chemical. Our approach in this work was thus
allowing the synthesis of an epoxy monomer from vanillin.21 to synthesize from vanillin a wide range of difunctional mono-
Other teams reported the synthesis of various biobased poly- mers directly usable in polymer synthesis. These synthesis
mers from vanillin. Thus, Meier et al. reported the synthesis of routes were chosen in order to optimize the yields and with a
polymers from vanillin and fatty acids by acyclic diene meta- reduced number of steps, to show the industrial potential of
thesis (ADMET).22 Starting from vanillin, Mialon et al. syn- this platform.
thesized polyesters such as polydihydroferulic acid23 and
We designed this platform with three vanillin derivatives as
polyethylene vanillate.24 Photoactive liquid crystalline poly- base chemicals, owing to their different oxidation states. This
esters and polyethers were also prepared from vanillin.25,26 An choice was based on the fact that lignin depolymerization
original benzoxazine monomer was prepared from vanillin often requires harsh oxidative or reductive conditions.31 Thus,
and furfurylamine by Sini et al. and then polymerized.27 it is mandatory to consider not only vanillin itself, as it is
Additionally, vanillin was methacrylated and used in the common in the literature, but also its different oxidative states
preparation of UV-curable palladium-chelating chitosan as potentially available. On the one hand, a vanillin 1 oxi-
derivatives.28 Vanillin methacrylate also replaced styrene in dation leads to vanillic acid 3 or even to a methoxyhydroqui-
vinyl-ester resins for composite application.29 Composites were none 2 in the case of a decarboxylation (strong oxidative and
Scheme 1 Vanillin platform for polymer synthesis.
1988 | Green Chem., 2014, 16, 1987–1998
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anion can exist. The reaction starts with a nucleophilic
addition of this hydroperoxide anion to the aldehyde carbonyl.
The final acidification of the mixture is important for two
reasons. Firstly, the pH of the solution becomes acidic, and
carbonates and hydroperoxide anions no longer exist in solu-
tion, thus stopping any further reaction. Secondly, the
aqueous phase must be acidic for the phenol form to predomi-
nate over the phenolate one in order to perform the extraction
efficiently.
Table 1 Functions present in the platform and their use in polymer
chemistry
Function of
monomers
Compounds
Targeted polymers
Epoxy resins
5, 6, 7
8, 9, 10
PolyHydroxyUrethanes (PHUs);
polycarbonates
The protocol used32 is very efficient and the handling
simple. Moreover, the oxidation reagent used, sodium percar-
bonate, has major advantages: it is inexpensive, large-scale
available as it is extensively used in the detergent industry as a
bleaching agent, easier to handle than a classic H2O2 solution
and, finally, respects sustainable development principles due
to its safety and environmental innocuity.
11, 12, 13
14, 15, 16
17, 18, 19
20, 21, 22
Polymers obtained by radical
polymerization
PolyUrethanes (PUs), polyesters,
polyacrylates, polycarbonates
Epoxy resins, PHUs, polyimides,
polyureas, polyamides
Epoxy resins, polyamides,
poly(vinyl-esters), polyesters
Glycidylation reactions
Glycidyl ethers 5, 6 and 7 were obtained respectively from the
three base chemicals 2, 3, and 4 in very good yields (≥87%).
We are the first, to our knowledge, to synthesize compounds 5
and 7. In a previous paper, Aouf et al. proved that aromatic
hydroxyl and acid functions readily react with epichlorohydrin
in the absence of a solvent.33 We adapted this method for the
synthesis of 5 and 6. The reaction mechanism is explained in
Scheme 3.
In a first step, a phase transfer catalyst (triethylbenzyl-
ammonium chloride – TEBAC) is used to allow the phenolate ion
to exist in organic solution. In a second step, this phenolate
ion reacts with epichlorohydrin via two possible mechanisms,
namely SN2 and ring opening. SN2 gives the expected glycidy-
lated product and ring opening leads to a chlorinated inter-
mediate. In a third step, this chlorinated intermediate is
closed by an intramolecular SN2 reaction in the presence of an
aqueous solution of NaOH and a phase transfer catalyst.
The synthesis of 7 starting from 4 was attempted with this
method. 4 possesses both a phenol and a benzyl alcohol. Glyci-
dylation only occurred on the phenol, and not on the benzyl
alcohol. This was explained by the fact that protons from
alkaline conditions32). On the other hand, reduction leads to
vanillyl alcohol 4. Our team functionalized these three mole-
cules, transforming them into a number of original biobased
monomers bearing well-known polymerizable functions and
thus creating the above-mentioned platform shown in
Scheme 1. Many of these compounds were prepared for the
first time.
The functions introduced in this platform and the types of
polymers in which they could be used are summarized in
Table 1.
Results and discussion
Platform base chemicals
Among the three platform base chemicals, vanillic acid 3 and
vanillyl alcohol 4 are quite common commercial compounds.
However, to the best of our knowledge, 2-methoxyhydroqui-
none 2 is not commercially available. It was thus prepared in
97% yield from vanillin by the Dakin reaction, ultimately
leading to one carbon loss. The reaction proceeds via the
mechanism shown in Scheme 2.
Sodium percarbonate dissociates in solution into H2O2 and
carbonate anions. As the solution is basic, a hydroperoxide
Scheme 3 Phenol glycidylation mechanism under solvent-free
Scheme 2 Mechanism of the vanillin Dakin oxidation.
conditions.
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Scheme 4 Mechanism of phenol glycidylation by a phase transfer catalysis system.
phenols are more acidic than protons from aliphatic alcohols.
Thus, contrary to phenolates, benzyl alcoholates cannot form
an ion pair with the phase transfer catalyst to exist in the
organic medium. It is worth noting that although this reacti-
vity difference is problematic here, it could be an advantage in
another context. In our case, 7 was synthesized using a bipha-
sic phase transfer catalysis system.34 The mechanism is shown
in Scheme 4.
Careful temperature control is mandatory as the reaction is
exothermic and any rise of temperature resulted in a colored,
crosslinked product.
These reactions do not require organic solvents since epi-
Scheme 5 Cyclic carbonate synthesis from an epoxy compound.
chlorohydrin is used as a reactive solvent. Epichlorohydrin was
employed as it is an industrial biobased compound via the
Epicerol® process from Solvay. Epoxy compounds 5, 6 and 7
have potential uses in high performance epoxy resins and
composites as they are biobased aromatic diglycidyl ethers.
Indeed, they are structurally similar to the current petrobased
epoxy monomers. They need to be tested as bisphenol A sub-
stitutes in terms of safety and material performances.
deal of interest over the past few years. These systems are actu-
ally synthesized by reaction between poly(cyclic carbonates)
with polyamines,35 leading to polyhydroxyurethanes (PHUs).
As these systems are shifting from academic studies to indus-
trial use, there is a growing need for bis(cyclic carbonates)
monomers and especially aromatic ones in substitution to
MDI or TDI for the synthesis of linear polymers. We thus syn-
thesized 8, 9 and 10 which are biobased, aromatic bis(cyclic
carbonates) usable in NIPU systems.
Carbonation reactions
Cyclic carbonate compounds 8, 9 and 10 were respectively syn-
thesized from the epoxy compounds 5, 6, and 7 previously
obtained. Compounds 8 and 10 were obtained quantitatively.
In the case of 9, undetermined side products were detected by
Allylation reactions
1H NMR, making this synthesis less interesting from an indus- Allylated compounds 11, 12 and 13 were respectively syn-
trial standpoint. However, there is, as far as we know, no other thesized from base chemicals 2, 3 and 4. A method used for
description of compounds 8, 9 and 10. These bifunctional the allylation of gallic acid has already been reported by our
cyclic carbonates were obtained by a LiBr-catalyzed CO2 inser- team.8 Compounds 11 and 12 were prepared quantitatively
tion into the oxirane rings35 as shown in Scheme 5.
using this method. A phenolate (or carboxylate) is first formed
The main advantage of this reaction is the use of CO2 as by the action of suspended potassium carbonate K2CO3. This
reactant. From a sustainable chemistry point of view, two phenolate (or carboxylate) is then allylated by an easy nucleo-
major challenges concern the polyurethane industry. The first philic attack on allyl bromide. As in the case of glycidylation,
one, true for the whole polymer industry, is to switch from the benzylic alcohol moiety in 4 is less reactive than phenols
petrobased to biobased resources. The second one, more specific or benzoic acids. Compound 4 was thus allylated by using the
to polyurethanes, is to avoid the use of isocyanate compounds same phase transfer catalysis system. The mechanism is also
since most of them (methylene diisocyanate – MDI, toluene the same as the one described in Scheme 4, the only difference
diisocyanate – TDI) are highly toxic or CMR, and are syn- being the use of allyl bromide instead of epichlorohydrin. It
thesized from phosgene, also highly toxic. Therefore, NIPU was found that phase transfer catalysis is a mild and efficient
(Non-Isocyanate PolyUrethane) systems have received a great process for the synthesis of 13 (86% yield).
1990 | Green Chem., 2014, 16, 1987–1998
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Allyl bromide is not a biobased compound. Since allylated
compounds can undergo radical polymerization and thiol–ene
click chemistry, compounds 11, 12 and 13 are therefore essen-
tial building blocks to establish our vanillin-based platform
for polymer chemistry.
Alcohol functionalization
Alcohol-functionalized compounds 14, 15 and 16 were
obtained in yields ≥90% under solvent-free conditions by
thiol–ene “click” addition of mercaptoethanol to allylated com-
pounds 11, 12 and 13 respectively. This work is the first
example, to the best of our knowledge, to report the synthesis
of compounds 14, 15 and 16.
Click chemistry is a concept now well established and has
received a lot of attention lately, especially in the field of sus-
tainable chemistry. Indeed, the click chemistry concepts of
efficient, versatile, and safe procedures with high atom
economy fit sustainable chemistry principles. Click chemistry
reactions are thus increasingly applied to renewable
resources.36
Thiol–ene coupling is considered as a click chemistry reac-
tion and has been extensively used in the polymer field.37 It
consists in the radical addition of a thiol onto a C–C double
bond. This coupling was for instance used by our team to syn-
thesize new biobased polyols from vegetable oils. Thiol–ene
coupling displays high yields and outstanding functional
group tolerance under simple reaction conditions. The reac-
tion can be initiated by either heat or UV irradiation, as in our
case.
Molecules 14, 15 and 16 are alcohol-functionalized bio-
based compounds bearing an aromatic ring. The aromatic ring
provides better thermo-mechanical properties to the material
than an aliphatic structure. They also bear primary aliphatic
alcohols, making them very reactive. Molecules 14, 15, and 16
could therefore bring interesting properties to polyesters or to
PU formulations.
Scheme 6 Material prepared from Product 5 and IPDA.
features. As for NIPU systems, tunable properties are needed
to fit to the application. These compounds are, to our knowl-
edge, the first non-aliphatic and biobased amine hardeners.
They could thus prove very useful from an industrial
standpoint.
Carboxylic acid functionalization
Acid-functionalized compounds 20, 21 and 22 were syn-
thesized by thiol–ene addition of 3-mercaptopropionic acid
onto 11, 12 and 13 respectively under solvent-free conditions.
To the best of our knowledge, compounds 20, 21 and 22 are
not mentioned in the literature.
In the first place, the reaction was attempted with thioglyco-
lic acid and was much faster but gave rise to unwanted side-
products. The literature reports such side-products, especially
thioesters, in the case of thioglycolic acid.38 Thus, the use of
3-mercaptopropionic acid was preferred over thioglycolic acid.
This reaction was slower than the other thiol–ene reactions
performed, especially in the case of 11 where only 68% were
converted to 20. 12 and 13 gave good conversions. However, no
side-products were detected.
Compounds 20, 21 and 22 also bear an aromatic ring that
may improve the thermo-mechanical properties of materials.
They are dicarboxylic acids and can thus be used as epoxy
resin hardeners and also as monomers in biobased polyesters.
Amine functionalization
Example of the material synthesized
Amine-functionalized compounds 17, 18 and 19 were syn-
thesized by thiol–ene addition of cysteamine hydrochloride Each type of compound is currently evaluated for the synthesis
onto 11, 12 and 13 respectively in yields ≥88%. Compounds of materials, especially NIPUs and epoxy polymers. These
17, 18 and 19 are also, as far as we know, described here for studies will be reported in detail in future articles. However, as
the first time. Cysteamine hydrochloride was preferred over an example of the potential use of these compounds, we chose
cysteamine because the amine moiety catalyzes the formation to prepare an epoxy material (Scheme 6) from Product 5. The
of disulfide bonds. Interestingly, thiol–ene addition was slower amine hardener chosen was the one most reported in the
with cysteamine hydrochloride than with mercaptoethanol. literature, IsoPhorone DiAmine (IPDA).
Amine-functional compounds were obtained by simple de-
protonation of the ammonium in a basic aqueous solution fol- material. By improving the formulation and the process, the Tg
lowed by an extraction with an organic solvent. could reach a value close to the one of the epoxy polymer pre-
Preliminary DSC results indicate a Tg of 117 °C for this
17, 18 and 19 are of great interest for epoxy thermosets and pared from DiGlycidylEther of bisphenol A (DGEBA) and IPDA,
NIPU manufacturing as they are biobased aromatic com- namely 158 °C.39 This material is the one most described in
pounds bearing two highly reactive primary amines. They can the literature and the one most used in industry. However,
thus react with epoxy and cyclocarbonate moieties. Moreover, DGEBA is derived from bisphenol A, a reprotoxic substance,5
hardeners with an aromatic structure will improve thermo- and thus needs to be replaced. The material prepared from
mechanical properties. Concerning epoxy thermosets, good Product 5 is a high-Tg, biobased alternative to the DGEBA–
thermo-mechanical properties are one of their characteristic IPDA system that will be investigated in future studies.
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13C NMR (100.6 MHz, acetone-d6, ppm) δ: 56.38 (s, C7);
101.40 (s, C2); 107.64 (s, C6); 116.13 (s, C5); 140.71 (s, C4);
149.07 (s, C3); 151.82 (s, C1).
Experimental
Materials and methods
Vanillin (99%) and vanillic acid (99%) were purchased from
ABCR. Vanillyl alcohol (98%), sodium percarbonate
Na2CO3·1.5H2O2 (available H2O2 20–30%), triethylbenzylam-
monium chloride (TEBAC) (99%), LiBr (99%), mercaptoethanol
(>99%), thioglycolic acid (>99%), 3-mercaptopropionic acid
(>99%), potassium carbonate K2CO3 (>99%), allyl bromide
(99%), IPDA (>99%), anhydrous sodium sulfate Na2SO4 (99%)
and HCl (37.5 wt%) and all solvents used (>99.5%) were pur-
chased from Sigma-Aldrich. Cysteamine hydrochloride (>97%)
and epichlorohydrin (>99%) were purchased from Fluka.
Sodium hydroxide, NaOH (99%), was purchased from Fisher.
All reactives were used as received.
HRMS (m/z, AP+): calculated: 140.0473; found: 140.0473.
Procedures for glycidylation (5, 6, 7)
This protocol was used for the preparation of 5 and 6 from 2
and 3. A round-bottomed flask was charged with 2 or 3 (1.0
eq.) and TEBAC (0.1 eq.). Epichlorohydrin (10.0 eq.) was added
and the mixture was stirred for 1 hour after reaching 80 °C.
The solution was then cooled down to room temperature. An
aqueous solution of TEBAC (0.1 eq.) and NaOH (4.0 eq.,
5.0 mol L−1) was added and the mixture was stirred for
30 minutes at room temperature. Ethyl acetate and deionized
water were then added. The mixture was stirred and the
aqueous phase was extracted with ethyl acetate. Organic
phases were combined, rinsed with brine and dried on anhy-
drous Na2SO4. Ethyl acetate and epichlorohydrin excess were
removed using a rotary evaporator. Further purification was
achieved by silica gel flash chromatography using a hexane–
ethyl acetate gradient as an eluent.
1H and 13C (APT mode) NMR spectra were recorded on a
400 MHz Brucker Aspect Spectrometer at room temperature.
Deuterated solvents used are given for each molecule. Chemi-
cal shifts are in ppm. Silica gel flash chromatography was per-
formed on a Grace Davison Reveleris device. UV irradiation
was performed in a Rayonet RPR-200 UV reactor equipped with
a cooling fan and 16 lamps of 35 W each with λmax = 254 nm. A
50 mL Paar autoclave equipped with an overhead stirrer was
used for carbonation reactions. MS measurements were per-
formed on a Waters Synapt G2-S High Resolution Mass
Spectrometer (HRMS) equipped with an ESI ionization source.
DSC analyses were carried out on a NETZSCH DSC200 calori-
meter at 20 °C min−1
.
Product 5: 2,2′-(((3-methoxy-1,4-phenylene)bis(oxy))bis(methy-
lene))bis(oxirane) (87%, m.p. 87 °C).
Synthesis of methoxyhydroquinone 2 from vanillin 1
1H NMR (400.1 MHz, acetone-d6, ppm) δ: 2.66 (m, 2H, H10a
,
A two-necked round-bottomed flask was charged with a solu-
tion of vanillin (0.25 mol L−1, 1.0 eq.) in THF. Deionized water
(40% vol.) was added. The mixture was degassed with nitrogen.
Sodium percarbonate (Na2CO3·1.5H2O2, 1.1 eq.) was then
added by portions under nitrogen and agitation. The reaction
was conducted for 3 hours at room temperature. Portions of a
HCl solution (0.1 mol L−1) were added to the mixture under
vigorous stirring until pH = 3 to quench the reaction. THF was
evaporated and the aqueous phase was extracted with ethyl
acetate. The organic phases were collected, washed with brine,
dried on anhydrous Na2SO4 and ethyl acetate was removed
under reduced pressure.
H
13a); 2.81 (m, 2H, H10b, H13b); 3.27 (m, 2H, H9, H12); 3.81 (m,
2H, H8a, H11a); 3.81 (s, 3H, H7); 4.23 (m, 2H, H8b, H11b); 6.43
(dd, JH H = 8.8 Hz, JH H = 2.8 Hz, 1H, H6); 6.63 (d, JH H =
6
3
4
4
6
5
6
2
2
2.8 Hz, 1H, H2); 6.88 (d,3JH H = 8.8 Hz, 1H, H5).
5
6
13C NMR (100.6 MHz, acetone-d6, ppm) δ: 44.91 (s, C10, C13);
51.16 (s, C12); 51.32 (s, C9); 56.63 (s, C7); 71.09 (s, C11); 72.89 (s,
C8); 102.57 (s, C2); 105.90 (s, C6); 117.37 (s, C5); 144.29 (s, C4);
152.51 (s, C3); 155.66 (s, C1).
HRMS (m/z, ES+, [M + H+]): calculated: 253.1079; found:
253.1076.
Product 2: methoxyhydroquinone (97%, m.p. 88 °C).
Product 6: oxiran-2-ylmethyl 3-methoxy-4-(oxiran-2-ylmethoxy)-
1H NMR (400.1 MHz, acetone-d6, ppm) δ: 3.77 (s, 3H, H7); benzoate (95%, m.p. 77 °C).
6.27 (dd, 3JH H = 8.4 Hz, 4JH H = 2.6 Hz, 1H, H6); 6.46 (d, 4JH H
1H NMR (400.1 MHz, CDCl3, ppm) δ: 2.72 (m, 1H, H14a); 2.77
= 2.6 Hz, 1H, H2); 6.63 (d, JH H = 8.4 Hz, 1H, H5); 6.86 (broad (m, 1H, H10a); 2.91 (m, 2H, H10b, H14b); 3.34 (m, 1H, H13); 3.40
6
5
2
2
6
3 6
5
6
s, 1H, H8); 7.73 (broad s, 1H, H9).
(m, 1H, H9); 3.92 (s, 3H, H11); 4.09 (m, 2H, H8a, H12a); 4.34 (dd,
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3
1H, H12b); 4.64 (m, 1H, H8b); 6.94 (d, JH H = 8.4 Hz, 1H, H5); the autoclave. The atmosphere was replaced with CO2 (P = 12
5
6
4
3
7.57 (d, JH H = 2.0 Hz, 1H, H2); 7.69 (dd, JH H = 8.4 Hz, bar), and then the solution was heated at 80 °C with continu-
2
6
6
5
4JH H = 2.0 Hz, 1H, H6).
ous stirring for 12 hours. The solvent was distilled under
6
2
13C NMR (100.6 MHz, CDCl3, ppm) δ: 44.68 (s, C10); 44.78 vacuum (P = 0.01 bar) at 60 °C. Deionized water was added and
(s, C14); 49.52 (s, C9); 49.90 (s, C13); 56.04 (s, C11); 65.37 the aqueous phase was extracted with ethyl acetate. The
(s, C8); 69.86 (s, C12); 112.29 (s, C5); 112.63 (s, C2); 122.85 organic phase was washed with brine, dried on anhydrous
(s, C1); 123.65 (s, C6); 149.05 (s, C3); 152.16 (s, C4); 165;92 Na2SO4 and ethyl acetate was removed using
(s, C7). evaporator.
HRMS (m/z, ES+, [M + H+]): calculated: 281.1025; found:
281.1025.
For the preparation of 7 from 4, a phase transfer catalysis
a rotary
system was used. A round-bottomed flask was charged with 4
(1.0 eq.) and TEBAC (0.1 eq.). Epichlorohydrin (10.0 eq.) was
added and the mixture was stirred for 4 hours until obtention
of a limpid pink solution. This solution was cooled down to
0 °C with an ice bath. A NaOH solution (33 wt%, 15.0 eq.) in
deionized water was prepared and poured into the cold
mixture under vigorous stirring. The reaction was conducted
overnight at room temperature (the ice bath was left to melt
over time). Deionized water was added to the mixture to dilute
4 times the NaOH solution. An equal volume of ethyl acetate
was added. The mixture was stirred and the aqueous phase
was extracted 2 more times with ethyl acetate. Organic phases
were combined, rinsed with brine and dried on anhydrous
Na2SO4. Ethyl acetate and epichlorohydrin excess were
removed using a rotary evaporator. Further purification was
achieved by silica gel flash chromatography using a hexane–
ethyl acetate gradient as an eluent.
Product 8: 4,4′-(((3-methoxy-1,4-phenylene)bis(oxy))bis(methy-
lene))bis(1,3-dioxolan-2-one) (100%, m.p. n.d.).
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 3.76 (s, 3H, H7); 4.16
(m, 4H, H8, H12); 4.39 (m, 2H, H10a, H14a); 4.61 (q, 2H, H10b
,
3
4
H
14b); 5.11 (m, 2H, H9, H13); 6.47 (dd, JH H = 8.8 Hz, JH H
2
=
6
5
6
2.8 Hz, 1H, H6); 6.63 (d, 4JH H = 2.8 Hz, 1H, H2); 6.93 (d, 3JH H
2
6
5
6
= 8.8 Hz, 1H, H5).
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 55.77 (s, C7); 65.95
(s, C14); 66.00 (s, C10); 67.91 (s, C12); 69.73 (s, C8); 74.88 (s,
C13); 75.12 (s, C9); 101.25 (s, C2); 104.76 (s, C6); 116.29 (s,
C5); 142.08 (s, C4); 150.53 (s, C3); 153.57 (s, C1); 154.87
(s, C11, C15).
HRMS (m/z, ASAP+, [M + H+]): calculated: 341.0871; found:
341.0873.
Product
7:
2-((3-methoxy-4-((oxiran-2-ylmethoxy)methyl)
phenoxy)methyl)oxirane (89%, m.p. 53 °C).
1H NMR (400.1 MHz, acetone-d6, ppm) δ: 2.53 (dd, 1H, H14a);
2.69 (m, 2H, H10a, H14b); 2.81 (m, 1H, H10b); 3.10 (m, 1H, H13);
3.30 (m, 2H, H9, H12a); 3.73 (dd, 1H, H12b); 3.82 (s, 3H, H7);
3.87 (dd, 1H, H8a); 4.28 (dd, 1H, H8b); 4.47 (d, 2H, H11); 6.86
Product 9: (2-oxo-1,3-dioxolan-4-yl)methyl 3-methoxy-4-((2-oxo-
1,3-dioxolan-4-yl)methoxy) benzoate (50%, m.p. n.d.).
3
4
3
(dd, JH H = 8.0 Hz, JH H = 1.6 Hz, 1H, H6); 6.94 (d, JH H =
6
6
5
6
2
5
8.0 Hz, 1H, H5); 6.98 (d, 4JH H = 1.6 Hz, 1H, H2).
1H NMR (400.1 MHz, acetone-d6, ppm) δ: 3.87 (s, 1H, H12);
4.42 (m, 2H, H13a, H13b); 4.58 (m, 4H, H8a, H8b, H10a, H15a);
2
6
13C NMR (100.6 MHz, acetone-d6, ppm) δ: 44.16 (s, C14);
44.49 (s, C10); 50.76 (s, C9); 51.28 (s, C13); 56.16 (s, C7);
71.39 (s, C8); 71.82 (s, C12); 73.42 (s, C11); 112.91 (s, C5); 114.76
(s, C2); 120.99 (s, C6); 132.93 (s, C1); 148.86 (s, C4); 150.75
(s, C3).
4.75 (m, 2H, H10b, H15b); 5.26 (m, 2H, H9, H14); 7.13 (d, 3JH H
=
5
6
4
8.4 Hz, 1H, H5); 7.55 (d, JH H = 2.0 Hz, 1H, H2); 7.62 (dd,
2
6
3JH H = 8.4 Hz, 4JH H = 2.0 Hz, 1H, H6).
6
5
6
2
13C NMR (100.6 MHz, acetone-d6, ppm) δ: 56.44 (s, C12);
65.08 (s, C8); 66.76 (s, C10); 67.29 (s, C15); 69.59 (s, C13); 75.29
(s, C9); 75.65 (s, C14); 113.76 (s, C5); 114.32 (s, C2); 123.87 (s,
C1); 124.23 (s, C6); 150.45 (s, C3); 153.27 (s, C4); 155.62 (s, C11);
155.74 (s, C16); 165.93 (s, C7).
−
−
HRMS (m/z, ASAP , [M ]): calculated: 266.1153; found:
266.1154.
Procedures for carbonation (8, 9, 10)
Epoxy-functionalized compound 8, 9 or 10 (1.0 eq.) and LiBr
HRMS (m/z, ES+, [M + Na+]): calculated: 391.0549; found:
(0.05 eq.) were stirred in acetone (35 mL) and introduced into 391.0549.
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13C NMR (100.6 MHz, acetone-d6, ppm) δ: 56.68 (s, C7); 70.27
(s, C11); 71.98 (s, C8); 102.73 (s, C2); 106.03 (s, C6); 117.24
(s, C5); 117.57 (s, C10); 117.71 (s, C13); 135.61 (s, C12); 136.02
(s, C9); 144.09 (s, C4); 152.56 (s, C3); 155.41 (s, C1).
HRMS (m/z, ES+, [M + H+]): calculated: 221.1178; found:
221.1178.
Product 10: 4-((2-methoxy-4-(((2-oxo-1,3-dioxolan-4-yl)methoxy)-
methyl)phenoxy)methyl)-1,3-dioxolan-2-one (100%, pale
yellow liq.).
1H NMR (400.1 MHz, CDCl3, ppm) δ: 3.62 (dd, 1H, H13a);
3.72 (dd, 1H, H13b); 3.86 (s, 3H, H7); 4.23 (dd, 2H, H8); 4.40
(dd, 1H, H15a); 4.60 (t, H15b); 4.54 (s, 2H, H12); 4.61 (d, 1H,
Product 12: allyl 4-(allyloxy)-3-methoxybenzoate (100%, brown
liq.).
H
10a); 4.63 (s, 1H, H10b); 4.83 (m, 1H, H14); 5.02 (m, 1H, H9);
3
4
6.82 (dd, JH H = 8.0 Hz, JH H = 1.2 Hz, 1H, H6); 6.90
6
5
6
2
1H NMR (400.1 MHz, CDCl3, ppm) δ: 3.93 (s, 3H, H11); 4.68
(d, 4JH H = 1.2 Hz, 1H, H2); 6.91 (d, 3JH H = 8.0 Hz, 1H, H5).
2
6
5
6
13C NMR (100.6 MHz, CDCl3, ppm) δ: 55.84 (s, C7); 66.15 (s,
C10); 66.19 (s, C19); 68.67 (s, C13); 69.22 (s, C8); 73.17 (s, C12);
74.48 (s, C9); 75.05 (s, C14); 111.78 (s, C2); 116.13 (s, C5); 120.14
(s, C6); 132.27 (s, C1); 147.10 (s, C4); 150.36 (s, C3); 154.76
(s, C11); 154.98 (s, C16).
(dt, 2H, H12); 4.81 (dt, 2H, H8); 5.30 (m, 2H, H10a, H14a); 5.42
3
(m, 2H, H10b, H14b); 6.06 (m, 2H, H9, H13); 6.89 (d, JH H
=
5
6
4
8.4 Hz, 1H, H5); 7.58 (d, JH H = 2.0 Hz, 1H, H2); 7.68 (dd,
2
6
3JH H = 8.4 Hz, 4JH H = 2.0 Hz, 1H, H6).
6
5
6
2
13C NMR (100.6 MHz, CDCl3, ppm) δ: 56.02 (s, C11); 65.50 (s,
C8); 69.69 (s, C12); 111.95 (s, C2); 112.40 (s, C5); 118.04 (s, C10);
118.49 (s, C14); 122.81 (s, C1); 123.44 (s, C6); 132.44 (s, C9);
132.54 (s, C13); 148.95 (s, C3); 152.04 (s, C4); 166.01 (s, C7).
HRMS (m/z, ES+, [M + H+]): calculated: 249.1126; found:
249.1127.
HRMS (m/z, ES+, [M + Na+]): calculated: 377.0854; found:
377.0849.
Procedures for allylation (11, 12, 13)
As in the case of the glycidylation of a benzyl alcohol
moiety, a phase transfer catalysis system was used for the
preparation of 13 from 4. A round-bottomed flask was charged
with 4 (1.0 eq.) and TEBAC (0.1 eq.). NaOH (5.0 eq.) was dis-
solved in water to obtain a 20 wt% solution. This solution was
poured into the flask and the suspension was stirred for
10 minutes while heating to 50 °C. Allyl bromide (4.0 eq.) was
then added to the mixture and the reaction was conducted for
5 hours. Deionized water was added and the mixture was
extracted with pentane. The organic phase was washed with
brine, dried on anhydrous Na2SO4 and pentane was removed
using a rotary evaporator. Further purification was achieved by
silica gel flash chromatography using a pentane–dichloro-
methane gradient as an eluent.
A first protocol was used for the preparation of 11 and 12 from
2 and 3. A two-necked round-bottomed flask was charged with
2 or 3 (1.0 eq.). Ethanol was added to obtain a 0.5 mol L−1
solution. The solution was cooled with an ice bath and K2CO3
(4.0 eq.) was added. After 10 minutes, allyl bromide (4.0 eq.)
was added dropwise using a syringe. The solution was stirred
for 30 minutes at 0 °C and then at room temperature for seven
days. Deionized water was added and the aqueous phase was
extracted with pentane. The organic phase was washed with
brine, dried on anhydrous Na2SO4 and pentane was removed
using a rotary evaporator. Further purification was achieved by
silica gel flash chromatography using a pentane–dichloro-
methane gradient as an eluent.
Product 11: 1,4-bis(allyloxy)-3-methoxybenzene (100%, pale
yellow liq.).
Product 13: 4-(allyloxy)-1-((allyloxy)methyl)-3-methoxy benzene
1H NMR (400.1 MHz, acetone-d6, ppm) δ: 3.80 (s, 3H, H7); (86%, pale yellow liq.).
4.48 (m, 4H, H8, H11); 5.20 (m, 2H, H10a, H13a); 5.38 (m, 2H,
1H NMR (400.1 MHz, acetone-d6, ppm) δ: 3.81 (s, 3H, H7);
10b, H13b); 6.05 (m, 2H, H9, H12); 6.42 (dd, JH H = 8.6 Hz, 3.98 (m, 2H, H12); 4.43 (s, 2H, H11); 4.55 (m, 2H, H8); 5.11–5.16
3
H
6
5
4JH H = 2.8 Hz, 1H, H6); 6.60 (d, JH H = 2.8 Hz, 1H, H2); 6.85 (m, 1H, H14a); 5.20–5.25 (m, 1H, H10a); 5.25–5.32 (m, 1H,
4
6
2
2
6
(d, 3JH H = 8.6 Hz, 1H, H5).
H
14b); 5.38–5.45 (m, 1H, H10b); 5.94 (m, 1H, H13); 6.08 (m, 1H,
5
6
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H9); 6.84 (dd, 4JH H = 2.0 Hz, 3JH H = 8.0 Hz, 1H, H6); 6.91 (dd,
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 27.78, 27.97 (2*s,
C11, C17); 28.85, 28.54 (2*s, C10, C16); 33.83, 33.89 (2*s, C18,
6
2
6
5
3JH H = 8.0 Hz, 1H, H5); 6.96 (dd, 3JH H = 2.0 Hz, 1H, H2).
5
6
2
6
13C NMR (100.6 MHz, acetone-d6, ppm) δ: 56.7 (s, C7); 70.9 (s, C12); 55.59 (s, C7); 60.82, 60.87 (2*s, C13, C19); 63.22 (s, C8);
C8); 71.9 (s, C12); 73.0 (s, C11); 113.4 (s, C2); 115.2 (s, C5); 116.9 66.87 (s, C15); 111.95, 112.10 (2*s, C2, C5); 121.97 (s, C1);
(s, C14); 117.8 (s, C10); 121.4 (s, C6); 133.3 (s, C1); 135.6 (s, C9); 123.14 (s, C6); 148.54 (s, C3); 152.20 (s, C4); 165.47 (s, C7).
136.9 (s, C13); 149.2 (s, C4); 151.3 (s, C3).
HRMS (m/z, ES+, [M + K+]): calculated: 443.0962; found:
−
HRMS (m/z, ASAP , [M − H+]): calculated: 233.1180; found: 443.0964.
233.1178.
Procedures for alcohol functionalization (14, 15, 16)
Allylated compound 11, 12 or 13 (1.0 eq.) and mercaptoethanol
(6.0 eq.) were mixed without adding any solvent. The solution
was irradiated in the UV reactor. The reactions were monitored
by 1H NMR.
Product 16: 2-((3-((4-(3-((2-hydroxyethyl)thio)propoxy)-3-meth-
oxybenzyl)oxy)propyl)thio)ethan-1-ol (100%, pale yellow liq.).
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 1.76 (m, 2H, H9);
1.93 (m, 2H, H16); 2.56 (m, 6H, H10, H11, H18); 2.66 (t, 2H, H17);
3.45 (t, 2H, H8); 3.52 (m, 4H, H12, H19); 3.75 (s, 3H, H14); 4.00
(t, 2H, H15); 4.36 (s, 2H, H7); 4.77 (m, 2H, H13, H20); 6.81 (dd,
3JH H = 8.0 Hz, 4JH H = 1.2 Hz, 1H, H6); 6.90 (d, 4JH H = 1.2 Hz,
6
5
6
2
2
6
1H, H2); 6.91 (d, 3JH H = 8.0 Hz, 1H, H5).
5
6
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 28.08 (s, C17); 28.43
(s, C10); 29.31 (s, C16); 29.84 (s, C9); 35.25 (s, C18); 35.29 (s,
C11); 55.93 (s, C14); 60.30 (s, C19); 60.34 (s, C12); 67.38 (s, C15);
68.34 (s, C8); 72.89 (s, C7); 111.65 (s, C5); 113.27 (s, C2); 120.32
(s, C6); 131.36 (s, C1); 147.80 (s, C3); 149.56 (s, C4).
HRMS (m/z, ES+, [M + H+]): calculated: 391.1611; found:
391.1613.
Product
14:
2,2′-((((3-methoxy-1,4-phenylene)bis(oxy))bis-
(propane-3,1-diyl))bis(sulfanediyl))diethanol (92%, pale
yellow liq.).
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 1.91 (m, 4H, H9,
H14); 2.57 (dt, 4H, H11, H16); 2.65 (dt, 4H, H10, H15); 3.53 (dt,
4H, H12, H17); 3.74 (s, 3H, H7); 3.93 (t, 2H, H8); 3.97 (t, 2H,
3
4
H13); 4.76 (m, 2H, H18, H19); 6.40 (dd, JH H = 8.8 Hz, JH H =
2
6
5
6
2.8 Hz, 1H, H6); 6.56 (d, 4JH H = 2.8 Hz, 1H, H2); 6.84 (d, 3JH H
2
6
5
6
Procedures for amine functionalization (17, 18, 19)
= 8.8 Hz, 1H, H5).
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 27.95 (s, C10, C15);
29.12 (s, C14); 29.29 (s, C9); 33.90 (s, C16, C11); 55.54 (s, C7);
60.86 (s, C12, C17); 66.33 (s, C13); 67.86 (s, C8); 101.02 (s, C2);
104.28 (s, C6); 115.03 (s, C5); 142.10 (s, C4); 150.26 (s, C3);
153.41 (s, C1).
Allylated compound 11, 12 or 13 (1.0 eq.) and cysteamine
hydrochloride (6.0 eq.) were dissolved in a minimum of metha-
nol. The solution was irradiated in the UV reactor. The reac-
tions were monitored by 1H NMR.
When the reaction was complete, the resulting mixture was
dissolved in water and K2CO3 was added to reach pH = 9. The
solution was then extracted with ethyl acetate, dried on anhy-
drous Na2SO4 and ethyl acetate was evaporated under reduced
pressure.
HRMS (m/z, ES+, [M + Na+]): calculated: 399.1277; found:
399.1276.
Product 15: 3-((2-hydroxyethyl)thio)propyl-4-(3-((2-hydroxy-
ethyl)thio)propoxy)-3-methoxybenzoate (96%, pale yellow liq.).
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 1.97 (m, 4H, H10, Product
17:
2,2′-((((3-methoxy-1,4-phenylene)bis(oxy))bis-
H16); 2.58 (2*t, 4H, H12, H18); 2.66 (2*t, 4H, H11, H17); 3.52 (m, (propane-3,1-diyl))bis(sulfanediyl))diethanamine (96%, pale
4H, H13, H19); 3.81 (s, 3H, H7); 4.11 (t, 2H, H15); 4.30 (t, 2H, yellow liq.).
3
H9); 4.87 (broad m, 2H, H14, H20); 7.07 (d, JH H = 8.4 Hz, 1H,
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 1.90 (m, 4H, H9,
5
6
3
4
H5); 7.45 (d, JH H = 2.0 Hz, 1H, H2); 7.57 (dd, JH H = 8.4 Hz, H14); 2.45–2.70 (m, 12H, H10, H11, H12, H15, H16, H17); 3.72 (s,
2
6
6
5
4JH H = 2.0 Hz, 1H, H6).
3H, H7); 3.94 (m, 4H, H8, H13); 6.39 (dd, JH H = 8.8 Hz,
6 5
3
6
2
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4
4JH H = 2.8 Hz, 1H, H6); 6.54 (d, JH H = 2.8 Hz, 1H, H2); 6.83 Procedures for acid functionalization (20, 21, 22)
6
2
2
6
(d, 3JH H = 8.8 Hz, 1H, H5).
5
6
Allylated compound 11, 12 or 13 (1.0 eq.) and 3-mercaptopro-
pionic acid (6.0 eq.) were mixed without adding any solvent.
The solution was irradiated in the UV reactor. The reactions
were monitored by 1H NMR.
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 27.50 (s, C15); 27.52
(s, C10); 29.14 (s, C14); 29.30 (s, C9); 35.23 (s, C16); 35.25 (s,
C11); 41.55 (s, C17); 41.57 (s, C12); 55.56 (s, C7); 66.34 (s, C13);
67.85 (s, C8); 101.00 (s, C2); 104.26 (s, C6); 114.98 (s, C5); 142.12
(s, C4); 150.27 (s, C3); 153.42 (s, C1).
HRMS (m/z, ES+, [M + H+]): calculated: 375.1779; found:
375.1776.
Product
20:
3,3′-((((3-methoxy-1,4-phenylene)bis(oxy))bis-
(propane-3,1-diyl))bis(sulfanediyl))dipropionic acid (68%, pale
yellow liq.).
Product 18: 3-((2-aminoethyl)thio)propyl-4-(3-((2aminoethyl)
thio) propoxy)-3-methoxybenzoate (93%, pale yellow liq.).
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 1.97 (m, 4H, H9,
H16); 2.52 (2*t, 4H, H11, H18); 2.63 (2*t, 4H, H10, H17); 2.68 (t,
4H, H12, H19); 3.82 (s, 3H, H14); 4.11 (t, 2H, H15); 4.30 (t, 2H,
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 1.91 (q, 4H, H9, H16);
2.51 (m, 4H, H13, H20); 6.66 (m, 8H, H10, H11, H17, H18); 3.73
3
(s, 3H, H7); 3.93 (t, 2H, H8); 3.96 (t, 2H, H15); 6.39 (dd, JH H
=
6
5
4
4
8.8 Hz, JH H = 2.8 Hz, 1H, H6); 6.56 (d, JH H = 2.8 Hz, 1H,
H2); 6.84 (d, JH H = 8.8 Hz, 1H, H5); 12.28 (broad s, 2H,
6
2
2
6
3
3
4
5
6
H8); 7.09 (d, JH H = 8.6 Hz, 1H, H5); 7.45 (d, JH H = 2.0 Hz,
5
6
2
6
H14, H21).
1H, H2); 7.58 (dd, 3JH H = 8.6 Hz, 4JH H = 2.0 Hz, 1H, H6).
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 26.36, 26.39 (2*s,
C11, C18); 27.59, 27.62 (2*s, C10, C17); 28.92, 29.08 (2*s, C9, C16);
34.45, 34.49 (2*s, C12, C19); 55.55 (s, C7); 66.33 (s, C8); 67.85 (s,
C15); 101.04 (s, C2); 104.31 (s, C6); 115.06 (s, C5); 142.11 (s, C4);
150.30 (s, C3); 153.44 (s, C1); 172.66 (s, C13, C20).
6
5
6
2
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 27.28 (s, C10); 27.47
(s, C17); 28.52 (s, C9); 28.83 (s, C16); 35.14, 35.16 (2*s, C11, C18);
41.52 (s, C12, C19); 55.59 (s, C14); 63.19 (s, C15); 66.87 (s, C8);
111.94 (s, C5); 112.09 (s, C2); 121.95 (s, C1); 123.13 (s, C6);
148.55 (s, C3); 152.20(s, C4); 165.44 (s, C7).
HRMS (m/z, ES+, [M + H+]): calculated: 433.1357; found:
433.1355.
HRMS (m/z, ES+, [M + H+]): calculated: 403.1721; found:
403.1725.
Product 19: 2-((3-((4-(3-((2-aminoethyl)thio)propoxy)-3-methoxy- Product 21: 3-((3-((4-(3-((2-carboxyethyl)thio)propoxy)-3-meth-
benzyl)oxy)propyl)thio)ethan-1-amine (88%, pale yellow liq.).
oxybenzoyl)oxy)propyl)thio)propanoic acid (92%, m.p. 68 °C).
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 1.76 (tt, 2H, H9);
1H NMR (400.1 MHz, (DMSO-d6, ppm) δ: 1.97 (m, 4H, H10,
1.94 (tt, 2H, H16); 2.52 (m, 3H, H10, H11, H18); 2.66 (m, 3H, H17); 2.51 (m, 4H, H13, H20); 2.67 (m, 8H, H11, H12, H18, H20);
H12, H17, H19); 3.46 (t, 1H, H8); 3.75 (s, 3H, H14); 4.01 (t, 1H, 3.81 (s, 3H, H7); 4.10 (t, 2H, H16); 4.29 (t, 2H, H9); 7.06 (d,
3
4
4
H15); 4.36 (s, 2H, H7); 6.81 (dd, JH H = 8.0 Hz, JH H = 1.2 Hz, 3JH H = 8.6 Hz, 1H, H5); 7.45 (d, JH H = 2.0 Hz, 1H, H2); 7.58
6
5
6
2
5
6
2
6
4
3
1H, H6); 6.90 (d, JH H = 1.2 Hz, 1H, H2); 6.91 (d, JH H
=
(dd, 3JH H = 8.6 Hz, 4JH H = 2.0 Hz, 1H, H6).
13C NMR (100.6 MHz, (DMSO-d6, ppm) δ: 26.31, 26.34 (2*s,
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 27.41 (s, C17); 27.78 C12, C19); 27.39, 27.63 (2*s, C11, C18); 28.34, 28.64 (2*s, C10
2
6
5
6
6
5
6
2
8.0 Hz, 1H, H5).
,
(s, C10); 29.10 (s, C16); 29.57 (s, C9); 35.19 (s, C18); 35.26 (s, C17); 34.42, 34.46 (2*s, C13, C20); 55.60 (s, C7); 63.22 (s, C9);
C11); 41.54 (s, C12, C19); 55.49 (s, C14); 66.91 (s, C15); 67.88 (s, 63.8 (s, C16); 111.94, 112.09 (2*s, C5, C2); 121.99 (s, C1); 123.18
C8); 71.77 (s, C7); 111.72 (s, C5); 113.11 (s, C2); 119.93 (s, C6); (s, C6); 148.57 (s, C3); 152.20 (s, C4); 165.49 (s, C7); 173.03
131.25 (s, C1); 147.33 (s, C4); 148.96 (s, C3).
HRMS (m/z, ES+, [M + H+]): calculated: 389.1932; found:
399.1933.
(s, C14, C21).
HRMS (m/z, ES+, [M + H+]): calculated: 461.1302; found:
461.1304.
1996 | Green Chem., 2014, 16, 1987–1998
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functionalized compounds are, to our knowledge, the first
non-aliphatic biobased amine hardeners, useful either in
epoxy or NIPU materials. The cyclic carbonate-functionalized
compounds could be useful to tune NIPU properties.
Products from the vanillin-derived methoxyhydroquinone
are especially interesting and versatile. Industrialization is
possible thanks to clean and straightforward syntheses and
there is no fragile bond on the methoxyhydroquinone that
could impact polymer properties.
In future studies, compounds from this platform should be
used in polymer formulations and thermo-mechanical pro-
perties of the corresponding materials should be tested.
Product 22: 3-((3-((4-(3-((2-carboxyethyl)thio)propoxy)-3-meth-
oxybenzyl)oxy)propyl)thio)propanoic acid (90%, liq.).
1H NMR (400.1 MHz, DMSO-d6, ppm) δ: 1.76 (quint., 2H,
H10); 1.93 (quint., 2H, H17); 2.51 (m, 6H, H11, H13, H20); 2.66
(m, 6H, H12, H18, H19); 3.45 (t, 2H, H9); 3.75 (s, 3H, H7); 4.00 (t,
3
4
2H, H16); 4.36 (s, 2H, H8); 6.81 (dd, JH H = 8.0 Hz, JH H = 2.0
6
5
4
63 2
Notes and references
Hz, 1H, H6); 6.90 (d, JH H = 2.0 Hz, 1H, H2); 6.91 (d, JH H
=
2
6
5
6
8.0 Hz, 1H, H5).
13C NMR (100.6 MHz, DMSO-d6, ppm) δ: 26.32, 26.42 (2*s,
C12, C19); 27.52, 27.91 (2*s, C11, C18); 28.91, 29.39 (2*s, C10
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67.88 (s, C9); 71.82 (s, C8); 111.67 (s, C2); 113.04 (s, C5); 119.99
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