WO2019202038A2 - Synthesis and polymerization of isosorbide-based monomethacrylates - Google Patents

Abstract

Isosorbide-5-methacrylate was obtained by enzymatic catalysis with Lipozyme RM IM in a highly regioselective manner in up to 87% yield. The process uses readily available acyl donors (methacrylic anydride or vinyl methacrylate), is easily scalable and chromatography free. Simple extractive workup followed by decoloration and filtration affords the monomer with up to > 99% purity. In addition, the developed enzymatic strategy was applied for the synthesis of a series of isosorbide 5- and 2-methacrylate derivatives. All the sythesized isosorbide monomethacrylates were radically polymerized with AIBN. The properties of these polymers with different side groups in either endo or exo configuration in the isosorbide structure was examined. The methacrylic isosorbide derivatives with OH-group were found to have very high glass transition temperature (T_g = 167 °C) and good thermal stability (at 5% weight loss under N₂, T_d,95 = 240 °C). The highest molecular weight (M_n = 80.6 kg/mol) was determined for the polymethacrylate with Ac-substitute.

Description

Synthesis and polymerization of isosorbide-based monomethacrylates

Technical Field

The present invention relates to a method of preparing isosorbide 5 -methacrylate, and in particular a method which uses Rhizomucor miehei lipase to carry out a regiospecific reaction. The invention also relates to a method of preparing isosorbide 2-methacrylate using a regiospecific reaction and a protecting group. The invention also relates to certain novel compounds no matter how they are made.

Background of the Invention

In recent decades, there has been an increasing interest in the utilization of renewable resources, since petroleum cannot be considered an infinite feedstock. Especially the conversion of lignocellulosic biomass into platform molecules or high-value chemicals has been extensively studied as biomass is the obvious source for sustainable carbon

compounds^{1 6}. Furthermore, bio-based polymers which can replace the products derived from petrochemical stocks have attracted significant interest in polymer synthesis^{1, 7 10}. Such polymeric materials that would interchangeably replace petroleum-based polymers, could reduce the usage of unrecoverable resources.

One very attractive compound due to rigidity, chirality, relative stability, and nontoxicity is isosorbide^{11, 12} (Scheme 1) - a platform molecule derived from biomass, more precisely from D-glucose by hydrogenation and double dehydration^{13, 14}. Isosorbide is a rigid bicyclic V- shaped compound, that has two secondary hydroxyl groups, one in endo position and the other in exo configuration^{15, 16}. Due to the relatively poor reactivity of the secondary alcohols¹⁷, various functionalized derivatives of isosorbide have been described^{18, 19}.

Additionally, in recent years many isosorbide-derivatives have be introduced into polymers^{20 23}. In most cases, isosorbide has been considered as a sustainable replacement for diol monomers derived from petroleum sources as the similarity comes from the two hydroxyl groups. Therefore polyesters, polyethers, polycarbonates, polyurethanes including the subunit of isosorbide have been synthesized²⁰. An interesting polyester is poly(ethylene-co- isosorbide)terephthalate, that has revealed a very high T_g value (above 200 °C) and at the same time, has great endurance towards decomposition (T_d,95 > 300 °C)²⁴. Also a high glass transition temperature of around 160 °C has been detected for poly(isosorbide carbonate)²⁵. Isosorbide-based epoxides have also been introduced into various polyethers and

polyurethanes.

Interestingly, in most cases and also, in all of these examples isosorbide has been

functionalized at both hydroxyl groups and therefore the subunit of isosorbide is entirely included in the polymer backbone. Less attention has been paid to the polymerization of mono functional isosorbide derivatives.

To slightly fill in this appealing research gap, we turned our attention to isosorbide monomethacrylates. Regio- and stereoselective lipase-catalyzed acylation of diols and polyols as well as alcoholysis and hydrolysis of the corresponding esters has been widely documented^{26 30}. Esterification reactions catalyzed by lipases have been described for isosorbide as well: 1) polyester synthesis^{31, 32}; 2) synthesis of mixtures of mono- and diesters³³; 3) synthesis of diesters³⁴ and 4) regioselective synthesis of monoesters^{35 40}.

Examples of both of the enzymatic regiopreferences towards the two hydroxyl groups of isosorbide in esterification have been demonstrated. However, by most of the lipases, the endo- 5 -OH group has been preferred. Lipozyme (RML) has been used to catalyze esterification of isosorbide with oleic acid affording a mixture of endo- 5-monooleate and er -2- mo noo lcatc with ratio of 3/1³⁷. Highly regioselective esterification of isosorbide (under solvent-free conditions) has been reported for octanoic acid as an acyl donor. Incubation at 60° C for 12 h of Lipozyme (0.5 g) impregnated (mediated with acetone solution) with a mixture of isosorbide (0.146 g, 1 mmol) and octanoic acid (0.288 g, 2 mmol) afforded isosorbide endo- 5-monooctanoic ester as sole product in good yield. In case of fatty acids with a shorter carbon chain like C6- (caproic) and C4- (butyric) acids, this method failed, affording products in very low yield even when using a very large excess of the acyl donor. For carboxylic acids with a carbon chain longer than C8 - Lipozyme catalyzed regioselective esterification of isosorbide affording 5 -monoesters with minor contaminations of the 2- regio isomers³⁸.

Lipase-catalyzed regioselective cleavage of isosorbide diacetate has afforded regioisomeric monoacetates³⁹. Enzymatic exo- 2-OH preference for isosorbide in esterification was exhibited by Rhizopus oryzae lipase, Bacillus protease, pig liver esterase and alkaline protease Subtilisin Carlsberg. Three former enzymes showed very low activity along with high regioselectivity while Subtilisin catalyzed transesterification of vinyl butyrate in THF affording a mixture of isosorbide 2-butyrate and 5-butyrate (ratio 71/15) in 62% yield⁴⁰. Lipase-catalyzed synthesis of acrylic and methacrylic esters of simple alcohols, including diols and triols⁴¹, as well as stereoselective synthesis of citronellyl methacrylate using different methacryl donors has been studied in detail^{42, 43}.

No lipase-catalyzed synthesis of isosorbide methacrylate has been described in the literature.

In a work dedicated to polymer synthesis - isomerically pure isosorbide 5 -methacrylate has been synthesized via a 5 -step pathway (overall yield 23 %)⁴⁴ and in another, chemical methods have been used to afford regioisomeric mixture of acetylated isosorbide

methacrylates⁴⁵. Isosorbide monomethacrylates have also been synthesized as mixtures of regioisomers by using simple chemical base- as well as acid-catalytic reactions and the products have been polymerized without separation^{46, 47}.

In conclusion, acylation of isosorbide catalyzed either by a heavy metal catalyst^{45, 48 51} like lead acetate and scandium triflate or by lipases is selective with regiopreference towards the sterically less accessible but structurally more reactive endo- 5-hydroxyl group; however, there are some exclusions cited above. Only a few esterifications with very high

regioselectivity have been reported for isosorbide, unfortunately, along with arguable process engineering and scalability. US 2017/0082936 Al (Xerox Coroporation) discloses methacrylate resins of at least one bio- based methacrylate monomer, where the monomer includes a rosin or isosorbide moiety obtained from natural sources, can be used in toner, carrier coating or both. A 1 : 1 mixture of endo/exo isomers (regioisomers) is prepared because the method used for the synthesis does not allow for the production of pure isomers. This is disadvantageous because the separation of isomers on a large scale is costly and complicated.

Mansoori et al.“Nanocomposite materials based on isosorbide methacrylate/Closite 20A” (Polymer International, vol. 62, no. 2, 2013, pages 280-288) discloses the alleged synthesis of isosorbide 5 -methacrylate in scheme 2. Mansoori et al. disclose also preparation of homopolymer of isosorbide 5 -methacrylate. However, there are serious doubts as to whether the polymer prepared by the authors is in fact true homopolymer. Because Mansoori et al. used qualitatively different list of components of starting (polymerized) mixture, as well as different preparation process. As a result, they obtained polymer with very different characteristics. The characterization data which are presented in Mansoori et al. in Table 2 (row 1) differ substantially from the results obtained by the present applicant. For instance, Mansoori et al. report Tg 73.6°C for the polymer 11 while we are reporting Tg = l67°C for the same one.

The IR spectra of the polymers also differ substantially. There can be observed certain distinct peaks, mainly characteristic to the ether frequencies, between 950 cm ¹ and 1200 cm ¹ in our spectrum while there is almost no distinct peaks but just multiple signals (curve) covering the same region (between 800 and 1300 cm ¹) in the IR spectrum of Mansoori et al. This refers to the substantially higher structural disorder of their polymer 11. In addition, their carbonyl signal is placed at 1733.0 cm ¹ while we report 1726.3 cm ¹ In conclusion, Mansoori et al. seem to be describing a substantially different product.

Summary of the Invention

In accordance with a first aspect of the invention, there is provided a method of preparing isosorbide 5 -methacrylate including the steps of reacting isosorbide with a methacrylate donor in the presence of Rhizomucor miehei lipase. In accordance with a second aspect of the invention, there is provided a method of preparing an isosorbide 5 -methacrylate diester, including the steps of carrying out a method as claimed in any preceding claim to prepare isosorbide 5 -methacrylate and then reacting the hydroxyl group at the 2-position of the isosorbide 5 -methacrylate with a compound having an acyl group. In accordance with a third aspect of the invention, there is provided an isosorbide 5- methacrylate diester having the formula shown in compounds 3, 5 and 7 below as well as the monomers pictured in the scheme 4a. :

Conditions: 3: acetic anydride, Et₃N, ACN, rt

5: vinyl laurate, Novozym 435, MTBE, rt

7: cyclohexanecarbonyl chloride, ACN/pyridine, rt

In accordance with a fourth aspect of the invention, there is provided a method of preparing isosorbide 2-methacrylate including the steps of:

(a) reacting isosorbide with a compound which includes a protecting group having acyl functionality in the presence of Rhizomucor miehei lipase in order to produce an isosorbide with a protecting group at the 5 -position,

(b) reacting the product of step (a) with a methacrylate donor in order to produce an isosorbide 2-methacrylate with a protecting group at the 5 -position, and

(c) hydrolysing the product of step (b) in order to remove the protecting group and form isosorbide 2-methacrylate.

In accordance with a fifth aspect of the invention, there is provided a method of preparing isosorbide 2-methacrylate-5 -acetate or isosorbide 2-methacrylate-5 -laurate including the steps of:

(a) reacting isosorbide with either vinyl acetate or vinyl laurate in the presence of

Rhizomucor miehei lipase in order to produce an isosorbide-5 -acetate or isosorbide-5-laurate, and

(b) reacting the product of step (a) with a methacrylate donor in order to produce isosorbide 2-methacrylate-5 -acetate or 2-methacrylate-5-laurate.

In accordance with a sixth aspect of the invention, there is provided a method of preparing a polymer including the steps of preparing a monomer as defined above, and then carrying out a polymerisation of said monomer with itself or of a mixture of two or more of said monomers or with any other monomer to produce a copolymer.

A number of preferred embodiments of the present invention will now be described, with reference to the following drawings, in which: Figure 1 is a graph showing the thermogravimetric analysis (TGA) profiles of polymers 11-17;

Figure 2 shows the differential scanning calorimetry (DSC) curves of polymers 11 and 12;

Figure 3 shows the DSC curves of polymers l3a-d; Figure 4 shows the DSC curves of polymers l4a-b;

Figure 5 shows the DSC curves of polymers 15, 16 and 17;

Figure 6 shows the size exclusion chromotography (SEC) in THF with differential refractive index (dRI) detector of polymers l3a-d;

Figure 7 shows the SEC in THF with differential refractive index (dRI) detector of polymers l4a-b; and

Figure 8 shows the SEC in THF with differential refractive index (dRI) detector of polymers 15, 16 and 17.

EXPERIMENTAL SECTION Materials. All reagents and solvents were obtained from commercial sources and were used without further purification.

Structural characterization. The structure of the monomers and polymers was performed by NMR spectroscopy using a Bruker 400 MHz spectrometer with the samples dissolved in either chloroform-^/ or dimethyl sulfoxide-^. The 1H NMR and ¹³C NMR were recorded at 400 and 100 MHz, respectively. The formation of polymers (11-17) from corresponding isosorbide methacrylate derivatives (1-7) was determined by the decrease or disappearance of the proton signals of the double bond CH₂=CH- between the 6.3-5.5 ppm region in comparison with the characteristic peaks of the polymers in 1H NMR spectra. The molecular weight of the polymers was determined by size-exclusion chromatography in THF. The SEC setup included three Shodex columns coupled in series (KF-805, -804, and - 802.5) situated in Shimadzu CTO-20A prominence column oven, Shimadzu RID-20A refractive index detector with Shimadzu LabSolution software. All samples were run at 40 °C in THF and at an elution rate of 1 mL/min. Calibration was done by using PEO standards (M_w = 3 860, 96 100 g/mol).

The intrinsic viscosity of the polymethacylates was determined using an Ubbelohde viscometer at 21 °C. Samples were dissolved in DMSO (11, 12, 13a-d, 14a-b) or in toluene (15-17). These stock solutions were later diluted by adding blank solution (DMSO or toluene) to reduce the concentrations. The efflux times of blank solution (ft,) and polymer solutions (t_s) through capillary were taken as the average of at least four measurements. The inherent (h,,,i,) and reduced (p_red) viscosity at different concentrations were calculated as:

The intrinsic viscosity [h] was estimated by extrapolating p_red and h,,,i, to c = 0 and calculating the average intersection with the y-axis.

Thermal characterization. Thermogravimetric analysis was performed using a TGA Q500 apparatus to determine the thermal stability of the polymers under a nitrogen atmosphere.

The temperature was increased from 50 °C to 600 °C at a heating rate of 10 °C/min. In order to remove solvent residues, the samples were kept isothermally at 120 °C during 20 min prior to the analysis. The thermal decomposition temperature (T_d,9₅) was determined at 5% weight loss. DSC analysis was carried out by using a DSC Q2000 differential scanning calorimeter. Dried samples were transferred to aluminum pans which were hermetically sealed. The samples were first heated to 150 °C, then cooled to 0 °C, and finally heated to 150 °C (except for polymers 11 and 12, which were heated up to 195 °C). The scan rate was 10 °C/min during the temperature program. The glass transition temperatures (T_g) was evaluated from the heating scans by identifying the inflection points.

RESULTS AND DISCUSSION

Design of a scalable enzymatic method.

The screening of conditions for the development of a highly regioselective lipase-catalyzed methacrylation method for isosorbide included: 1) finding the proper lipase (and its loading) together with corresponding proper 2) solvent and a proper 3) acyl donor. Acyl donors’ reactivity, concentration and optimum excess should also be taken into consideration. An important issue is how to destroy the excess of a certain acyl donor after the reaction is over and which separation methodology can be used for the purification of the product. Design of easily separable end products is of utmost importance when designing a scalable synthesis. Also determined should be: 4) process temperature and 5) process engineering (agitation, mass transfer - stirring or shaking influence on the enzyme granules, etc.), 6) influence of acyl donors’ metabolite(s) on the enzyme activity, 7) duration of the process. The latter, as a rule, can be shortened by increasing the loading of the immobilized enzyme. The immobilized lipases widely used in organic synthesis, Novozym 435 (Candida antarctica lipase B (CalB)), Lipozyme RM IM (Rhizomucor miehei lipase (RML)) and Lipolase TL IM (Thermo myces lanuginosus lipase (TLL)) were explored. CalB is an atypical lipase with an active site well accessible in different media and known as a good synthetic catalyst while RML and TLL are recognized as mainly hydrolytic enzymes with different active site and catalytic performance.

Solvents tested were toluene, n-hexane, cyclohexane, benzene, acetonitrile, methyl tert-butyl ether. Methacryl donors used were vinyl methacrylate and the considerably cheaper methacrylic anhydride that has not been used as an acyl donor in lipase-catalyzed methacrylations. However, some other carboxylic acid anhydrides, unlike too active carboxylic halides have been used^{52, 53}.

The synthesis of 5-methacrylate 1. (Scheme 1)

When isosorbide was treated with vinyl methacrylate at RT in the presence of Lipozyme RM IM in MTBE, only the endo regioisomer 1 was formed as a product (method A, Scheme 1). When the conversion reached about 90-95%, the reaction was terminated by filtering off the enzyme. Simple extraction (EtO Ac/sat. aq. NaHCCf and brine) was performed, followed by decolorization with activated charcoal in ethanol. After filtration, hydroquinone was added as a stabilizer, and the solution was evaporated to afford 1 in >99% purity and 87% yield. The product contained only traces of ethanol and hydroquinone by 1H NMR as impurities; neither 2-methacrylate nor bis-methacrylate were detected. Endo- configuration of methacrylate was determined by 2D FT NMR experiments. The yield obtained corresponds nearby to optimum between the following conditions: enzyme and acyl donor loading, duration of the process and water washing efficiency (isosorbide 5 -methacrylate is rather hydrophilic and has to be washed carefully with water solutions). This is the first highly regioselective, one-step synthesis of this monomer. CalB was non-regiospecific under any conditions tested. TLL, despite being a structural counterpart of RML, was, unexpectedly, about 10 times less active in catalyzing methacrylation of isosorbide than RML.

For methacrylic anhydride, used as an acyl donor instead of vinyl methacrylate, under similar reaction conditions (method B, Scheme 1) - Lipozyme RM IM in MTBE catalyzed the acylation of endo- 5 -OH of isosorbide in a highly regioselective manner. When the conversion reached roughly 95%, water was added to hydrolyze enzymatically the unreacted methacrylic anhydride and thereafter the enzyme was filtered off. The product 1 was isolated by a simple extractive workup/decolorization and gained in 74% yield. The lower yield is probably obtained because of a larger volume of NaHCCE solution used to extract the considerably larger quantity of methacrylic acid liberated from the acyl donor. The product was purified exactly the same way as above in the vinyl methacrylate case (charcoal/EtOH, filtration, evaporation) and gained with purity >95%. The product contained small amounts of non- isomeric byproducts, formed due to impurities in the methacrylic anhydride used. It is noteworthy, that the method A affords a highly pure product via both, green synthesis and green separation methodology which could be suitable for biomedical applications. Lipozyme RM IM could be reused in case of both methods. However, some decrease in activity (up to 20%) was observed after the first run and to ensure an efficient biocatalyst reuse, corresponding treatment and optimization is needed. The decrease of activity is probably due to both the high reactivity of methacrylic moiety as well as the acetaldehyde liberated from vinyl methacrylate which may have a detrimental influence on the enzyme. Although the two developed methods A and B have some differences, most notably the use of different acyl source, both of them offer simple chromatography-free access to monomer 1 in excellent regioselectivity, purity and high yield. This novel synthesis is easily scalable, making it appealing for potential industrial production.

Scheme 1. Regioselective synthesis of 5 -methacrylate 1.

The synthesis of isosorbide 5-acetate 4a was performed by method A (Scheme 1) except vinyl acetate was used as an acyl donor. The product obtained after decolorization with charcoal in ethanol, filtration and evaporation was 98% pure, containing trace amount of bis- acetate that was separated by chromatography. Isosorbide 5-laurate 6a was also synthesized following method A (Scheme 1) in highly regioselective manner in good yield and purified over silica in order to separate the unreacted acyl donor, vinyl laurate (yield: 92%). Unreacted isosorbide is easy to extract with water and therefore no excess of vinyl laurate can be used if so decided, however, some lauric acid is always formed in low- water enzymatic systems and full separation by basic extraction only is complicated for this soap.

The synthesis of isosorbide 5-methacrylic diesters.

5 -Methacrylate 1 in hand was converted into various diesters as monomers for

polymerization studies (Scheme 2): 1) isosorbide 2-acetate-5 -methacrylate 3 was synthesized by routine base-catalyzed (Et₃N in CH₃CN) acetylation using acetic anhydride (yield: 93%); 2) isosorbide 2-cyclohexanecarboxylate-5-methacrylate 7 was synthesized in the same manner using cyclohexanecarbonyl chloride, the product was separated by crystallization from ethanol solution (yield: 61%) and 3) isosorbide 2-laurate-5 -methacrylate 5 was obtained by CalB-catalyzed (CalB has low selectivity towards isosorbide OH groups and can be used to acylate both of them) acylation of the 2-OH group of isosorbide 5 -methacrylate with vinyl laurate in CH₃CN (yield: 58%), in all cases the reaction conditions were not optimized.

The synthesis of 2-methacrylic monomers.

Next, we turned our attention to isosorbide exo-2-methacrylate 2 and corresponding diesters thereof. Isosorbide methacrylate 2 has a methacryloyl group in exo- position and is thereby a regio isomer of compound 1. The direct regioselective 2-OH functionalization is challenging, as the lipases are selective towards 5-OH in isosorbide. Thus, 2-OH functionalization requires a somewhat different approach (Scheme 3). However, we applied a strategy, which takes advantage of Lipozyme RM IM high 5-OH selectivity. Isosorbide was acetylated, as mentioned above, catalyzed by RML, in a highly regioselective manner. In the crude reaction mixture, no regioisomeric 2-acetate, but a trace amount of isosorbide bis-acetate was detected and separated. Treatment of isosorbide 5-acetate 4a with methacrylic anhydride in the presence of Et₃N in CH₃CN afforded isosorbide 2-methacrylate-5-acetate 4 in 95% yield.

In turn, Novozym 435 catalyzed highly regioselective methano lysis of acetyl group in 4 affording isosorbide 2-methacrylate 2 in 97% yield after chromatography. And finally, isosorbide 2-methacrylate-5-laurate 6 was prepared by methacrylation of isosorbide 5- laurate (synthesis described above) 6a with methacrylic anhydride. Attention: a stabilizing agent (hydroquinone or HQ monomethyl ether) was added before evaporation to any separated methacrylic product.

Conditions: 3: acetic anydride, Et₃N, ACN, rt

5: vinyl laurate, Novozym 435, MTBE, rt

7: cyclohexanecarbonyl chloride, ACN/pyridine, rt

Scheme 2. Synthesis of various bis-esters 3, 5, and 7 from 1.

5 Scheme 3: Synthesis of exo-methacrylic isosorbide monomers 2, 4 and 6. Polymerization of isosorbide-based monomethacrylates.

All the synthesized monomers (1-7) were polymerized radically with azobisisobutyronitrile (AIBN) at 60 °C for 24 h (Scheme 1). The Table 1 provides an overview of obtained polymers (11-17). The Figures of SEC, DSC and the solubility examined in different solvents of polymers 11-17 is presented the Supporting Information section below.

Scheme 4. Radical polymerization of a) isosorbide e«c/o-methacrylates, b) isosorbide exo-methacrylates.

A further version of Scheme 4a) is given below, in which monomers M1-M10 and corresponding polymers P1-P10 are identified (in addition to monomers 3 and 5 and corresponding polymers 13 and 15 identified above).

The invention also includes monomers and corresponding polymers made according to Scheme 4a) in which R is defined as follows:

R = A= H, OH, Oalkyl, alkyl, and combinations thereof

wherein the identity of A in each case is the same or different. In a preferred embodiment, R is as defined below:

The synthesis of this monomer (identified as Ml 1) and the corresponding polymer (Pl 1) is described in the detailed synthesis section below.

A further version of Scheme 4b) is given below, identifying additional monomer M12 and P12 in addition to monomer 6 and polymer 16 identified above:

R— - / (GHn-42J \_m fUUni₃ m = 10 and 16 have been prepared

M12 m = 16 P12 m = 16

6 m = 10 16 m = 10

Table 1. Radical polymerization of different isosorbide-based monomethacrylates.

13a

0.5

34.1 2.5 0.30 223 133

13b

0.25 82 45.7 2.0 0.34 n.df 133

13c

0.13 70 64.3 1.9 0.37 n.df 132

13d

0.06 66 80.7 1.9 0.45 n.df 136

14a

0.5 89 26.6 2.7 0.28 210 129

14b

0.13 78 64.6 2.1 0.39 n.df 130

15

0.5 87 41.8 2.6 0.33^g 226 66

10 16

0.5

45.8 2.4 0.32^g 222 54

1 1 17

0.5 89 41.1 2.7 0.33^g 208 129

“Monomer conversion determined by NMR.⁶Determined by SEC in THF.“Intrinsic viscosity measured at 21 °C in DMSO solutions. ^Determined by TGA at 5% weight loss under \>.“Determined by DSC under \ An.d. - not determined, intrinsic viscosity measured in toluene solutions. ^Melting peak was seen in DSC graph T_m = 83 °C.

First we polymerized hydroxy- functional mono-methacrylates 1 and 2 in DMSO to obtain polymethacryates 11 and 12, correspondingly (Table 1, entires 1 and 2). Thermogravimetric analysis (TGA) showed a T_d,95 of 238 °C and 240 °C under N₂, respectively (Figure 1).

Analysis with differential scanning calorimetry (DSC) revealed very high T_g values, 167 °C for both polymers 11 and 12 (Figure 2). The number-average molar mass (M_n) of polymers 11 and 12 was not possible to determine by SEC as these polymers did not dissolve in THF nor in CHCI3 (Table Sl, Supporting Information section). Instead the viscosity of these polymers were measured. The intrinsic viscosity of the hydroxy- functional polymers turned out to be higher than for other synthesized polymers. For polymer 11 it was very high, [h] = 0.82 dL g the authors are speculating that this particular polymer induces hydrogen bonds between different chainunits as the free OH-group is in exo position. Polymer 12 from the isomeric endo- hydroxy-monomer doesn’t have lower intrinsic viscosity than 11, [h] = 0.46 dL g The reason might be intramolecular hydrogen bonds that exist in isosorbide structure because of the endo configuration of the hydroxyl group at C5 position⁵⁴.

Next we turned our attention to the polymerization of exo-acetate-isosorbide-methacrylate 3. This was carried out using different AIBN concentrations: 0.5, 0.25, 0.13, and 0.06 mole percent (Table 1, entries 3-6). As it can be seen from the table, the conversion of the monomer 3 is the highest (88%) for the experiment with the 0.5 mol% AIBN and the lowest converison of 66% was determined for the experiment with 0.06 mol% AIBN. The SEC analysis for polymers 13a-d showed an increase of M_n which is in correspondence with the decrease of AIBN amount, as predicted (Figure 6). The highest M_n of 80.6 kg moL¹ with a low B = 1.9 was determined for polymer 13d. The viscosity of polymers 13a-d also showed an increasing trend according to the enlargement of the M_n. The highest viscosity (0.45 dL g

¹ ) was measured for 13d which has a resembling value compared to hydroxy-functional polymer 12. The T_d,95 for polymers 13a was determined to be 223 °C under N₂ (Figure 1), similar value of T_d,95 (251 °C) under inert atmosphere was reported previously for this polymer prepared also by free radical polymerization³⁴. The DSC analysis of 13a-d had no significant differences, but 13d had the highest T_g (136 °C) of those four polymers (Figure 3).

The radical polymerization of endo- acetate-monomer 4 to polymethacrylates 14a and 14b (Table 1, entries 7 and 8) gave similar results as monomer 3. When 0.5 mol% of AIBN was used, the polymer 14a with a M_n of 26.6 kg mo ¹ and D = 2.7 was obtained (Figure 7). The M_n value was somewhat smaller and the polydisperity a bit higher than for the polymer 13a that was received with the same AIBN amount. With 0.13 mol% AIBN the analysis results of 14b were more identical to 13b, as the M_n of 14b was 64.6 kg mo ¹ and D = 2.1. The T_d,95 for polymer 14a was determined to be 210 °C being about 10 degrees lower than for 13a (Figure 1). The glass transition temperature of 14a and 14b appeared to be 129 °C and 130 °C, respectively (Figure 2). The viscosity of the two polymers was in correspondence with the increase of M_n value exhibiting 0.28 and 0.39 dL g^-1 for 14a and 14b, accordingly. Turning to polymers 15 and 16 (Table 1, entries 9 and 10), the polymerization of methacrylates 5 and 6 with a long alkyl chain substitute in exo or endo position respectively, gave polymers with M_n of 41.8 and 45.8 kg mob¹, correspondingly (Figure 8). The polydispersity index remained larger than 2 in both cases. The T_d,95 values of these two polymers were comparable to 13a-d and 14a-b, showing the T ₉₅ of 226 °C for 15 and 222 °C for 16 (Figure 1). Although the TGA results were similar to previous polymers, the T_g values of 15 and 16 were much lower, 66 °C and 54 °C, accordingly (Figure 5). The lower Tg value is caused by the long alkyl chain that can move more freely and which increases the free volume in the molecule. In case of polymer 15 a melting peak (T_m = 83 T_d.95) was seen in DSC graph. Interestingly, polymer 16 did not exhibit any melting peak during DSC analysis. This differences might also be caused by the different exo-endo configuration of the two isomeric monomers. The intrinsic viscosity of 15 (0.33 dL g ' ) and 16 (0.32 dL g ') were measured in toluene, as these two polymers are not soluble in DMSO (Table Sl, Supporting Information section).

Finally, monomer 7 with a cyclohexylcarboxylate substitute in exo configuration was polymerized with AIBN (Table 1, entry 11). The resulting polymer 17 had M_n of 41.1 kg moF¹ and D = 2.7 (Figure S7, Supporting Information). This polymer showed the lowest T_d,95 value of 208 °C (Figure 1), but the T_g (129 °C) was equal to polymer 14a (Figure 5). The intrinsic viscosity of 17 (0.33 dL g^-1), which was also measured in toluene, had no significant difference compared to polymers 15 and 16.

Overall, the obtained polymers demonstrate that the substitute in the structure of isosorbide- based methacrylate is relevant, as it dictates the properties of the corresponding polymers. It can be seen that monomer 5 and 6 with a long carbon chain provided polymers with low T_g values. On the contrary, hydroxy- functional monomers 1 and 2 gave polymethacrylates with very high T_g values, which could be used in coating applications.

A conclusion about the difference of exo-endo configuration of the monomers can also be drawn. No significant difference was seen during the polymerization reaction with different exo/en o-methacrylates, as conversion of the monomer and the properties of the polymers are similar in all cases depending on the amount of the added AIBN. For example, polymers 11 and 12 have identical T_g values and very close TGA results. Only the intrinsic viscosity has a large difference, which is most likely brought about by the occurence of the hydrogen bonds between chains in polymer 11. There was also equal values of T_g in case of 13a-b and 14a-b. Moreover, the polymers with long alkyl chain 15 and 16 have both low T_g values

differentially to other polymer obtained. However, only 15 showed a melting peaks in DSC analysis, which is probably the effect of the exo- position of alkyl chain unit.

CONCLUSION

In summary, novel easily scalable chromatography- free synthesis pathway for the 5- methacrylate-isosorbide was demonstrated by the catalysis of Lipozyme RM IM with two acyl donors. In both cases excellent regioselectivity, purity and high yield was detected. Acetate-, laurate- and cyclohexanecarboxylate-derived 5 -methacrylate isosorbides were also obtained.

The isomeric 2-methacrylic isosorbide needed a longer synthesis strategy and procedure included acetylation of isosorbide with RML catalysis, following addition of methacrylic anhydride, and the subsequent Novozym 435 catalyzed methano lysis of the acetyl group. The 5-laurate and 5-acetate monomers from 2-methacrylate isosorbide were also synthesized.

As follows, the obtained seven monomethacrylic isosorbide monomers with different substituents were polymerized by free radical polymerization with AIBN. It could be seen, that the substitute in the isosorbide structure is relevant, as it dictates the polymer properties. The monomers with free hydroxyl-group provided polymers with higher T_g and T_d,95 values compared to currently available corresponding reference polymers. The acetate-functional polymers had somewhat lower T_g values, but it was shown that the molecular weight of those polymers was possible to change in correspondance with the added AIBN during the radical polymerization. On the contrary to previous, the polymers with long alkyl chain substitute demonstrated low T_g values and even exhibited a melting peak, but the decomposition temperature was still over 200 °C.

Furthermore, it was found, that the position of methacrylate group in either exo or endo configuration has no significant impact on the polymerization reaction, as the similar properties for the polymers was seen. To conclude, polymers with a molecular weight up to 80 kg mol^-1, T_d,95 up to 240 °C and T_g over 165 °C were obtained. Not only, these new isosorbide monomethacrylates expand the usability of isosorbide in different applications, but also, the corresponding

polymethacrylates have high potential to contribute to the growing area of bio-based polymers.

DETAILED SYNTHESIS

Synthesis of monomethacrylic isosorbide monomers.

D-isosorbide 5 -methacrylate 1 (the acyl donor used: vinyl methacrylate).

Into a 1 L flask were introduced: D-isosorbide (21.92 g, 0.15 mol), methyl /erf-butyl ether (300 mL), vinyl methacrylate (33.64 g, 36 mL, 0.30 mol), and Lipozyme RM IM (4.0 g). The mixture was slowly stirred at 20 °C for 60 h. After that the ratio of the unreacted D- isosorbide and the target monoester was estimated to be less than 1/10 by TLC. The synthesis was terminated by filtering off the enzyme. The filtrate was evaporated and the residual crude product was dissolved in EtOAc (500 mL) and washed with saturated NaHCCh solution (2x50 mL) and brine (2x30 mL). Hydroquinone (2 mg) was added to the solution, which was further dried over anhydrous Na₂S0₄, filtered and evaporated. The oily crude product was dissolved in ethanol (95.6% EtOH/H₂0; 300 mL), activated charcoal (2.0 g) was added and the mixture was stirred at 20 °C for 12 h. The charcoal was filtered off using a glass filter covered with filter aid Hyflo® Super Cel® layer (CAS: 68855-54-9). An additional 2 mg of hydroquinone was added to the ethanol solution before evaporation, which afforded 28.24 g (yield: 87.3%) of colourless oily target D-isosorbide 5 -methacrylate. Endo- configuration of the methacrylate was confirmed by 2D LT NMR experiments. The purity of the product was >99% as determined by 1H NMR spectroscopy. The product contained traces of EtOH and hydroquinone.

1H NMR (800 MHz, CDCl₃) d 6.13 (dq, J= 1.5 and 3x1.0 Hz, 1H, H-3mE), 5.600 (p, J=4xl.5Hz, 1H, H-3mZ), 5.17 (td, J= 2x5.6 and 4.5 Hz, 1H H-5x), 4.87 (ddt, J=5.6, 4.7 and 2x0.5 Hz, 1H, H-4x), 4.37 (dt, J=4.7 and 2x0.9 Hz, 1H, H-3x), 4.28 (dtd, J=3.2, 2x0.9 and 0.5 Hz, 1H, H-2n), 3.89 (dd, , J=l0.l and 5.6 Hz, 1H, H-6x), 3.87 (dt, J=l0.0 and 2x0.9 Hz, 1H, H-lx), 3.83 (ddt, J=l0.l, 4.5 and 2x0.4 Hz, 1H, H-6n), 3.82 (ddt, J=l0.0, 3.2 and 2x0.4 Hz, 1H, H-ln), 3.06 (bs, 1H, OH), 1.93 (dd, 3H, J=l.O and 1.5 Hz, H-4m).

¹³C NMR (201 MHz, CDCl₃) d: 166.74 (C-lm), 135.52 (C-2m), 126.34 (C-3m), 88.18 (C3), 80.40 (C4), 75.85 (C2), 75.31 (Cl), 74.18 (C5), 70.53 (C6), 18.22 (C-4m). [a]²⁰o +69.8 (c 1.3, CHCl₃); [a]²⁰ _D +74.6 (c 2.4, EtOAc);

IR (neat; v, cm ¹): 461, 654, 775, 813, 851, 914, 951, 976, 1014, 1091, 1171, 1299, 1455, 1637, 1721, 2876, 2931, 3434.

HRMS (ESI): calcd for Ci₀Hi₄O₅Na [M + Na]⁺ 237.0733, found 237.0732.

MS (m/z): 215, 171, 154, 128, 113, 98, 85, 70, 69, 68, 57, 43, 41. TLC: R_f = 0.21 (PE/EtOAc 1/1).

The alternative synthesis of D-isosorbide 5-methacrylate 1 (the acyl donor used: methacrylic anhydride).

Into a 1 L flask were introduced: D-isosorbide (21.92 g, 0.15 mol), methyl tert-butyl ether (300 mL), methacrylic anhydride (34.7 g, 33.5 mL, 0.225 mol) and Lipozyme RM IM (4.0 g).

The mixture was stirred at 20 °C for 40 h. The ratio of the unreacted D-isosorbide vs. the target 5-monoester was estimated by TLC to be ca 1/20. Neither the regioisomeric 2- methacrylate nor isosorbide bismethacrylate were detected by TLC. In order to destroy the excess of methacrylic anhydride, water (3.6 mL, 0.2 mol) was added and stirring of the reaction mixture was continued for an additional 24 h, until no anhydride was detected in the mixture by TLC. The synthesis was terminated by filtering off the enzyme. The filtrate was evaporated, the residual crude product was dissolved in EtOAc (500 mL) and washed with saturated NaHC0₃ solution (2x75 mL) in order to eliminate unreacted isosorbide as well as methacrylic acid formed, and finally with brine (2x30 mL). The solution was dried over anhydrous Na₂S0₄, filtered and 2 mg of hydroquinone was added. The solution was evaporated, the residual oily product was dissolved in ethanol (95.6%), activated charcoal (2.0 g) was added and the mixture was stirred at 20 °C for 12 h. The charcoal was filtered off through a glass filter covered with filter aid Hyflo® Super Cel® layer (CAS: 68855-54-9).

An additional 2 mg of hydroquinone was added to the ethanol solution and the solution was evaporated to afford 23.97 g (yield: 74.6%) of target D-isosorbide 5 -methacrylate with >95% purity.

Characterization of the product is given in the former example.

D-isosorbide 2-methacrylate 2.

The starting D-isosorbide 2-methacrylate-5 -acetate 4 (2.23 g, 8.70 mmol) containing

HQMME was dissolved in acetonitrile (28.8 mL) and methanol (1.2 mL) was added. To catalyze methano lysis - immobilized Candida antarctica lipase B (Novozym 435; 0.8 g) was introduced into the reaction vessel. The process was monitored by TLC until complete conversion was reached after shaking the mixture at RT for 48 h. The enzyme was filtered off, the filtrate was evaporated and the residual substance was chromatographed over silica gel. Hydroquinone (1 mg) was added to the collected fractions; evaporation afforded 1.81 g of isosorbide 2-monomethacrylate (yield: 97.4%).

1H NMR (800 MHz, CDCfi) d 6.13 (dq, J=l.5 and 3x1.0 Hz, 1H, H-3mE), 5.62 (p, 4x1.5 Hz, 1H, H-3mZ), 5.28 (dtd, J= 3.6, 2x1.0 and 0.6 Hz, 0.6, 1H H-2n), 4.65 (ddt, J= 5.4, 4.4 and 2x0.5 Hz, 1H, H-4), 4.53 (dt, J= 4.4 and 2x1.0 Hz, 1H, H-3x), 4.32 (dtd, J= 7.5, 2x6.0 and 5.4 Hz, 1H, H-5x), 4.09 (dtt, , J= 10.7, 2x0.9 and 2x0.5 Hz, 1H, H-lx), 4.05 (dddd, J= 10.7, 3.6, 0.5 and 0.4 Hz, 1H, H-ln), 3.91 (dd, J= 9.5 and 6.0, Hz, 1H, H-6x), 3.58 (ddd, J= 9.7, 6.1 and 0.5 Hz, 1H, H-6n), 2.67 (d, J= 7.5 Hz, 1H, C5-OH), 1.94 (dd, J= 1.6 and 1.0 Hz, 3H, H-4m).

¹³C NMR (201 MHz, CDC13) d 166.25 (C-lm), 135.60 (C-2m), 126.61 (C-3m), 85.56 (C-3), 81.94 (C-4), 78.55 (C-2), 73.58 (C-l), 73.45 (C-6), 72.28 (C-5), 18.19 (C-4m). [a]²⁰o +68.2 (c 1.1, CHCfi).

IR (ATR) v_max (cm^-1): 3433, 1717, 1636, 1161, 1084, 1049. HRMS (ESI): calcd for Ci₀Hi₄O₅Na [M + Na]⁺ 237.0733, found 237.0733.

TLC: R_f = 0.37 (PE/EtOAc 1/1); flash chromatography eluent: PE/EtOAc 3/2.

D-isosorbide 2-acetate-5-methacrylate 3. D-Isosorbide 5 -methacrylate 1 (2.57 g, 12 mmol) containing ca 200 ppm of hydroquinone was dissolved in acetonitrile (60 mL). Acetic anhydride (2.45 g, 2.27 mL, 24 mmol) was added on stirring followed by triethylamine (4.86 g, 6.7 mL, 48 mmol). The mixture was stirred at RT for 24 h, then the conversion was almost complete by TLC. Methanol (1.6 g, 2 mL, 50 mmol) was added and the mixture was allowed to stir overnight (14 h).The mixture was evaporated; the residual substance was dissolved in ethyl acetate (80 mL) and washed with saturated NaHCCf solution (3x30 mL) and brine (2x20 mL). The solution was dried over anhydrous Na₂S0₄, filtered and hydroquinone (2 mg) was added. After evaporation, the target diester was purified by short-column chromatography over silica gel (2 mg of hydroquinone monomethyl ether was added to the collected fractions prior to evaporation) to afford a pure product (2.87 g, yield: 93.2%).

1H NMR (800 MHz, CDCl₃) d 6.17 (dq, J= 1.5 and 3x 1.0 Hz, 1H, H-3mE), 5.63 (p, J= 4x1.5 Hz, 1H, H-3mZ), 5.22 (td, J= 2x5.7 and 4.7 Hz, 1H, H-5), 5.19 (dtd, J= 3.4, 2x0.9 and 0.7 Hz, 1H, H-2), 4.90 (dddd, J= 5.6, 4.9, 0.7 and 0.5 Hz, 1H, H-4), 4.50 (dt, J= 4.9 and 2x0.9 Hz, 1H, H-3), 3.97 (m, 1H, H-lx), 3.96 (m, 1H, H-ln), 3.94 (dd, J= 10.1 and 5.7 Hz, 1H, H- 6x), 3.90 (ddt, J= 10.1, 4.8 and 2x0.5 Hz, 1H, H-6n), 2.08 (3H, s, H-2a), 1.97 (dd, J= 1.6 and

1.0 Hz, H-4m).

¹³C NMR (201 MHz, CDCl₃) d 170.20 (C-la), 166.57 (C-lm), 135.56 (C-2m), 126.96 (C- 3m), 85.91 (C-3), 80.85 (C-4), 77.97 (C-2), 74.01 (C-5), 73.30 (C-l), 70.66 (C-6), 20.90 (C- 2a), 18.36 (C-4m). [a]²⁰o +97.1 (c 1.6, CHCl₃).

IR (ATR) v_max (cm^-1): 1736, 1636, 1373, 1234, 1165, 1096. HRMS (ESI): calcd for Ci₂Hi₆0₆Na [M + Na]⁺ 279.0839, found 279.0839.

TLC: R_f = 0.40 (PE/EtOAc 1/1); flash chromatography eluent: PE/EtOAc 5/1.

D-isosorbide 2 -methacrylate- 5-acetate 4. D-Isosorbide 5-acetate 4a (2.82 g, 15 mmol) was dissolved in acetonitrile (75 mL).

Methacrylic anhydride (3.08 g, 2.98 mL, 20 mmol) was added followed by triethylamine (4.05 g, 5.58 mL, 40 mmol). The mixture was stirred at RT for 48 h, methanol (0.8 g, 1.0 mL, 25 mmol) was added and stirring was continued for 12 h. The mixture was evaporated, the residual substance was dissolved in EtOAc (80 mL), washed with a saturated solution of NaHCCf (2x30 mL) and brine (2x20 mL). The solution was dried over anhydrous Na₂S0₄, filtered, hydroquinone monomehyl ether (1 mg) was added and the solution was evaporated. The crude product was further purified by column chromatography over silica gel. Prior to evaporation of collected fractions hydroquinone monomethyl ether (1 mg) was added; 3.687 g of the target diester was gained (yield: 95.9%). 1H NMR (800 MHz, CDCfi) d 6.12 (dq, J= 1.5 and 3x1.0 Hz, 1H, qd, H-3mE), 5.62 (p, J=

4x1.5 Hz, 1H, H-3mZ), 5.26 (dddd, J= 3.4, 1.3, 0.9 and 0.7 Hz, 1H, H-2), 5.16 (ddd, J= 6.1, 5.6 and 5.4 Hz, 1H, H-5), 4.86 (ddt, J= 5.4, 4.6 and 2x0.5 Hz, 1H, H-4), 4.54 (dt, J= 4.6 and 2x0.9 Hz, 1H, H-3), 4.05 (dd, J= 10.7 and 3.4 Hz, 1H, H-ln), 4.03 (ddd, J= 10.7, 1.3 and 0.9 Hz, 1H, H-lx), 3.97 (dd, J= 9.7 and 6.1 Hz, 1H, H-6x), 3.82 (ddd, J= 9.7, 5.6 and 0.6 Hz, 1H, H-6n), 2.17 (s, 3H, H-2a), 1.94 (dd, J= 1.6 and 1.0 Hz, 3H, H-4m).

¹³C NMR (201 MHz, CDCfi), d 170.43 (C-la), 166.32 (C-lm), 135.61 (C-2m), 126.62 (C- 3m), 85.82 (C-3), 80.69 (C-4), 78.17 (C-2), 73.97 (C-5), 73.46 (C-l), 70.10 (C-6), 20.68 (C- 2a), 18.18 (C-4m).

[a]²⁰o +123.0 (c 1.3, CHCfi). IR (ATR) v_max (cm^-1): 1721, 1636, 1373, 1238, 1161, 1096.

HRMS (ESI): calcd for Ci₂Hi₆0₆Na [M + Na]⁺ 279.0839, found 279.0840. TLC: Rf = 0.40 (PE/EtOAc 2/1); flash chromatography eluent: PE/EtOAc 5/1.

D-isosorbide 2 -laurate- 5 -methacrylate 5.

D-Isosorbide 5 -methacrylate 1 (2.10 g, 9.8 mmol) was dissolved in methyl tert-butyl ether (30 mL), vinyl laurate (2.88, 3.30 mL, 12.74 mmol) was added followed by catalyst

Novozym 435 (2.0 g). After incubation of the mixture at 55 °C for 48 h on stirring, the enzyme was filtered off. The filtrate was evaporated and the target diester was purified by short column chromatography over silica gel to afford 2.241 g (yield: 57.7%) of the target compound. 1H NMR (800 MHz, CDCb) 5 6.17 (dq, J= 1.5 and 3x 1.0 Hz, 1H, H-3mE), 5.63 (p, J= 4x1.5 Hz, 1H, H-3mZ), 5.21 (td, 2x5.7 and 4.8 Hz, 1H, H-5), 5.20 (m, 1H, H-2), 4.89 (ddt, J= 5.4, 4.9 and 2x 0.5 Hz, 1H, H-4), 4.49 (dt, J= 4.8 and 2x0.9 Hz, 1H, H-3), 3.97 (dd, J= 10.7 and 3.2 Hz, 1H, H-ln), 3.96 (dd, J= 10.0 and 5.7 Hz, 1H, H-6x), 3.95 (ddd, J= 10.7, 1.2 and 0.9 Hz, 1H, H-lx), 3.89 (dddd, J= 10.0, 4.8, 0.5 and 0.3 Hz, 1H, H-6n), 2.31 (dd, J= 7.9 and 7.3 Hz, 2H, H-21), 1.97 (dd, J= 1.5 and 1.0 Hz, 3H, H-4m), 1.60 (m, 2H, H-3m), 1.30-1.23 (m, 16H, H-3 - Hl 11), 0.88 (t, J= 7.2 Hz, 3H, H-121).

¹³C NMR (201 MHz, CDCl₃) 5 172.94 (C-ll), 166.65 (C-lm), 135.56 (C-2m), 126.41 (C- 3m), 85.98 (C-3), 80.86 (C-4), 77.71 (C-2), 74.06 (C-5), 73.43 (C-l), 70.63 (C-6), 34.12 (C- 21), 31.87 (C-101), 29.560 (C-61), 29.55 (C-71), 29.40 (C-51), 29.30 (C-81), 29.19 (C-41), 29.03 (C-91), 24.80 (C-31), 22.66 (C-l 11), 18.31 (C-4m), 14.12 (C-121).

[a]²°o +44.82 (c l.l, EtOAc);

IR (ATR) v_max (cm^-1): 1724, 1638, 1458, 1159, 1096, 758.

HRMS (ESI): calcd for C₂₂H₃₇O₆ [M + H]⁺ 397.2585, found 397.2574.

TLC: R_f = 0.19 (PE/EtOAc 10/1); flash chromatography eluent: PE/EtOAc 10/0.6. D-isosorbide 2 -methacrylate- 5 -laur ate 6.

D-Isosorbide 5-laurate 6a (1.774 g, 5.4 mmol) was dissolved in acetonitrile (40 mL), methacrylic anhydride (1.249 g, 8.1 mmol) was added followed by triethylamine (1.23 g, 1.7 mL, 12.15 mmol). The mixture was stirred at RT for 48 h. TLC analysis indicated complete conversion of the starting material. Methanol (320 mg, 0.4 mL, 10 mmol) was added and the mixture was stirred for further 16 h. The mixture was evaporated, the residual substance was dissolved in EtOAc (70 mL) and washed with NaHCCh saturated solution (2x25 mL) and brine (2x15 mL), the solution was dried over anhydrous Na₂S0₄, filtered and evaporated. Purification of the product over silica gel afforded 1.869 g of homogeneous target compound (yield: 87.2%).

1H NMR (800 MHz, CDCl₃) d 6.12 (dq, J= 1.5 and 3x 1.0 Hz, 1H, H-3mE), 5.61 (p, J= 4x1.5 Hz, 1H, H-3mZ), 5.26 (dddd, J= 3.1, 1.5, 0.9 and 0.6 Hz, H-2), 5.16 (dt, J= 6.1 and 2x5.4 Hz, 1H, H-5), 4.86 (ddt, J= 5.4, 4.7 and 2x0.5 Hz, 1H, H-4), 4.53 (ddd, J= 4.7, 0.9 and 0.7 Hz,

1H, H-3), 4.02 (dd, J= 10.7 and 3.1 Hz, 1H, Hln), 4.01 (ddd, J= 10.7, 1.4 and 0.6 Hz, 1H, H- lx), 3.96 (dd, J= 9.8 and 6.0 Hz, 1H, H-6x), 3.82 (ddd, J= 9.8, 5.4 and 0.6 Hz, 1H, H-6n), 2.37 (m, 2H, H-21), 1.93 (dd, J= 1.6 and 1.0 Hz, 3H, H-4m), 1.64 (m, 2H, H-31), 1.34-1.23 (m, 16H, H-3 - Hl 11), 0.88 (t, J= 7.2 Hz, 3H, H-121).

¹³C NMR (200 MHz, CDCl₃) d 173.26 (C-ll), 166.32 (C-lm), 135.60 (C-2m), 126.59 (C- 3m), 85.84 (C-3), 80.71 (C-4), 78.17 (C-2), 73.71 (C-5), 73.35 (C-l), 70.29 (C-6), 33.92 (C- 21), 31.87 (C-101), 29.56, 29.56, 29.41, 29.30, 29.22 (C-(4l-8l)), 29.03 (C-91), 24.83 (C-31),

22.66 (C-l 11), 18.18 (C-4m), 14.11 (C-121).

[a]²⁰o +81.2 (c 1.2, EtOAc).

IR (ATR) v_max (cm^-1): 1724, 1636, 1458, 1157, 1096, 756.

HRMS (ESI): calcd for C₂₂H₃₇0₆ [M + H]⁺ 397.2585, found 397.2569. TLC: R_f = 0.16 (PE/EtOAc 10/1); flash chromatography eluent: PE/EtOAc 10/0.7. D-isosorbide 2-cyclohexanecarboxylate-5-methacrylate 7.

D-Isosorbide 5 -methacrylate 1 (2.057 g, 9.6 mmol) was dissolved in acetonitrile (50 mL), triethylamine (5 mL) was added to the solution. Cyclohexaneearbonyl chloride (1.7 g, 1.55 mL, 11.6 mmol) was added dropwise on stirring at RT. Stirring was continued at RT ovenight (16 h); TLC analysis indicated incomplete conversion. An additional quantity of cyclohexaneearbonyl chloride (0.66 g, 0.6 mL, 4.5 mmol) was added and stirring was continued for addidtional 24 h. Methanol (640 mg, 0.8 mL, 20 mmol) was added and the mixture was allowed to stir for another 3 h. The reaction mixture was evaporated; ethyl acetate (80 mL) was added to the residual substance and the solution obtained was washed with saturated NaHCCf solution (2x30 mL) and brine (2x15 mL). The solution was dried over anhydrous Na₂S0₄, filtered and evaporated. The product was recrystallized from ethanol (20 mL) at -6 °C to afford 1.911 g of the target diester (yield: 61.4%).

1H NMR (800 MHz, CDCl₃) d 6.17 (dq, J= 1.6 and 3x1.0 Hz, 1H, H-3m), 5.630 (p, J= 4x1.5 Hz, 1H, H-3m), 5.21 (td, J= 2x5.6 and 4.9 Hz, 1H, H-5), 5.19 (dddd, J= 3.4, 1.2, 0.9 and 0.7 Hz, 1H, H-2), 4.891 (ddt, J= 5.3, 4.8 and 2x0.5 Hz, 1H, H-4), 4.47 (dt, J= 4.8 and 2x0.9 Hz, 1H, H-3), 3.97 (dd, J= 10.6 and 3.4 Hz, 1H, H-ln), 3.96 (dd, J= 10.0 and 5.8 Hz, 1H, H-6x), 3.93 (dt, J= 10.6 and 2x0.9 Hz, 1H, H-lx), 3.89 (ddt, J= 10.0, 5.1 and 2x0.5 Hz, 1H, H-6n), 2.30 (tt, J= 2x11.3 and 2x 3.6 Hz, 1H, H-lc), 1.97 (dd, J= 1.6 and 1.0 Hz, 3H, H-4m), 1.87 and 1.42 (m, 2+2H, H-2, 6c, eq and ax), 1.74 and 1.27 (m, 2+2H, H-3, 5c, eq and ax), 1.64 and 1.22 (m, 2H, H-4 eq and ax).

¹³C NMR (201 MHz, CDCl₃) d 175.14 (COc), 166.66 (C-lm), 135.56 (C-2m), 126.40 (C- 3m), 85.98 (C-3), 80.84 (C-4), 77.50 (C-2), 74.10 (C-5), 73.47 (C-l), 70.57 (C-6), 42.85 (C- lc), 28.80/28.78 (C-2, 6c), 25.59 (C-4c), 25.24/25.23 (C-3, 5c), 18.31 (C-4m).

[a]²⁰o +79.3 (c 0.6, EtOAc). IR (ATR) v_max (cm^-1): 1724, 1636, 1161, 1096, 756.

HRMS (ESI): calcd for C₁₇H₂₅O₆ [M + H]⁺ 325.1646, found 325.1632.

TLC: R_f = 0.13 (PE/EtOAc 10/1). D-isosorbide 5-acetate 4a.

D-Isosorbide (4.38 g; 30 mmol) was introduced into a 250 mL flask on magnetic stirrer, metyl tert-butyl ether (60 mL) was added followed by vinyl acetate (12.9 g; 13.8 mL; 150 mmol) on stirring. The acetylation was started by adding a catalyst - Lipozym RM IM (2.0 g). The reaction mixture was stirred at RT for 79 hrs. Conversion of the starting material was estimated by TLC to be -95%.

The synthesis was terminated by filtering off the enzyme. The filtrate was evaporated to afford 5.8 g of crude product, that was purified by column chromataography over silica gel. The target compound was gained with 88% yield (4.97 g). 1H NMR (800 MHz, CDCl₃) d 5.10 (dt, J= 6.0 and 2x5.3 Hz, 1H, H-5), 4.81 (dddd, J= 5.3, 4.6, 0.6 and 0.5 Hz, 1H, H-4), 4.36 (dt, J= 4.6 and 2x1.0 Hz, 1H, H-3), 4.28 (1H, bm, H-2), 3.88 (dt, J= 10.0 and 2x0.9 Hz, 1H, H-lx), 3.88 (dd, J= 9.8 and 6.0 Hz, 1H, H-6x), 3.84 (dd, J= 10.0 and 3.3 Hz, 1H, H-ln), 3.73 (ddd, J= 9.8, 5.3 and 0.6 Hz, 1H, H-6n), 3.12 (bs, 1H, OH), 2.09 (s, 3H, H-2a). ¹³C NMR (201 MHz, CDCl₃) d 170.61 (C-la), 88.04 (C-3), 80.20 (C-4), 75.88 (C-2), 75.42

(C-l), 74.05 (C-5), 70.00 (C-6), 20.61 (C-2a).

[a]²⁰o +112.92 (c 2.3, EtOAc);

TLC: R_f = 0.14 (PE/EtOAc 4/5); R_f = 0.30 (PE/EtOAC 1/4); flash chromatography eluent: PE/EtOAc 4/5.

D-isosorbide 5-laurate 6a.

D-Isosorbide (2.19 g, 15 mmol) and methyl tert-butyl ether (50 mL) were introduced into a 250 mL flask on a magnetic stirrer. Vinyl laurate (5.09 g, 5.83 mL, 22.5 mmol) was added followed by a catalyst - Lipozym RM IM (1.0 g). The mixture was stirred for 48 h at RT. After the monitoring by TLC had confirmed the conversion rate to be higher than 90%, the process was terminated by filtering off the enzyme. The filtrate was evaporated and the target compound was purified by flash chromatography over silica gel. Homogeneous isosorbide 5- laurate (4.523 g) was gained with 91.8% yield.

1H NMR (800 MHz, CDCfi) d 5.14 (ddd, J= 5.9, 5.4 and 5.1 Hz, 1H, H-5), 4.84 (ddt, J= 5.4, 4.6 and 2x0.6 Hz, 1H, H-4), 4.39 (dt, J= 4.9 and 2x0.9 Hz, 1H, H-3), 4.31 (dtd, J= 3.2, 2x0.9 and 0.6 0.9 Hz, 1H, H-2), 3.90 (dt, J= 10.0 and 2x0.9 Hz, 1H, H-lx), 3.90 (dd, J= 9.8 and 7.9 Hz, 1H, H-6x), 3.86 (dd, J= 10.1 and 3.2 Hz, 1H, H-ln), 3.76 (ddd, J= 9.8, 5.1 and 0.6 Hz, 1H, H-6n), 2.48 (bs, 1H, OH), 2.36 and 2.35 (m, 2H, H-21), 1.62 (m, 2H, H-31), 1.33-1.23 (m, 16H, H-(4l-l 11), 0.87 (t, J= 7.2, 3H, H-121).

¹³C NMR (201 MHz, CDCfi) d 173.36 (C-ll), 88.13 (C-3), 80.28 (C-4), 76.08 (C-2), 75.39 (C-l), 73.80 (C-5), 70.27 (C-6); 33.91 (C-21), 31.84 (C-101), 29.55, 29.54, 29.40, 29.28,

29.20, 29.02 (C-(4l-9l)), 24.79 (C-31), 22.63 (C-l 11), 14.08 (C-121).

[a]²⁰o +68.87 (c l.5, EtOAc);

TLC: R_f = 0.29 (PE/EtOAc 1/1); flash chromatography eluent: PE/EtOAc 2/1.

D-Isosorbide-2-Eicosanoate-5-Methacrylate Ml

D-Isosorbide 5 -methacrylate (360 mg, 1.68 mmol) was dissolved in dry dichloromethane (2 mL). Reaction flask was purged with argon. Eicosanoyl chloride (918 mg, 2.77 mmol) was dissolved in dichloromethane (1 mL) and added dropwise simultaneously with triethylamine (0.75 mL) to the reaction mixture. Reaction was left stirring for overnight. Reaction progress was checked by TLC. After terminating the reaction, extraction with sodium bicarbonate solution was carried out. Organic phases were collected, dried over magnesiumsulfate and concentrated. Mixture was purified by short silica column. Fractions were collected and concentrated under reduced pressure. Crude conversion was 95%, reaction gave white crystals 592 mg (isolated yield: 69.2%) ^lH NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, %_H=0.9 HZ, CH_2£, 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, lH), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_4x, 1H), 4.48 (m, CH_3x, 1H), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH₂_ _2e, 2H), 1.96 (dd, ⁴J_HH=1.5 HZ, %_H=0.9 HZ, CH_3-ma, 3H), 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2-4-19e, 3 OH), 0.87 (t, ³J_HH = 7.0 Hz, CH_3.20e, 3H). ¹³C NMR (100.6 MHz, CDC1₃) d: 172.89 (CO_C2o), 166.65 (CO_ma), 135.66 (C_ma), 126.30 (CH_2-ma), 86.05 (CH_C3), 80.88 (CH_2.C4), 77.81 (CH_2.C2), 74.11 (CH_C5), 73.46 (CH_2.CI), 70.61 (CH_C6), 34.16 (CH_2.C2e), 31.91 (CH_2.C3e), 29.6-29.7 (CH_2.C4-i _e), 29.58 (CH_2.Ci3e), 29.42 (CH_2.Ci4e), 29.34 (C¾a_5e), 29.21 (CH_2.ci6e), 29.06 (CH_2.ci_7e), 24.83 (CH_2.Ci8e), 22.67 (CH_2.Ci9e), 18.28 (CH_3-ma), 14.10 (CH,_C20e). HRMS (ESI): calcd for C30H56O6Na [M + Na]+ 531.36561, found 531.36328.

D-Isosorbide-2-Octadecanoate-5-Methacrylate M2

Obtained by the same method as Ml. Crude conversion >95%, isolated yield 65.4%

H NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, %H=0.9 HZ, CH_2/ , 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, lH), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_2-4x, 1H), 4.48 (m,

CH_3x, lH), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH_2-2e, 2H), 1.96 (dd, ⁴J_HH=1.5 Hz, ⁴JHH=0.9 HZ, CH_3.ma, 3H), 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2-4_i_7e, 28H), 0.88 (t, ³JHH^— 7.1 Hz, CH₃_i_8e, 3H).

¹³C NMR (100.6 MHz, CDC1₃) d: 172.89 (COcis), 166.65 (CO_ma), 135.66 (C_ma), 126.30 (CH_2-ma), 86.05 (CH_C3), 80.88 (CH_2.C4), 77.81 (CH_2.C2), 74.1 1 (CH_C5), 73.46 (CH_2.CI), 70.61 (CH_C6), 34.16

(CH_2.C2e), 31.91 (CH_2.C3), 29.6-29.7 (CH_2.C4-io_e), 29.58 (CH_2.Cn_e), 29.42 (CH_2.Ci2e), 29.34 (CH_2.Ci3e), 29.21 (CH_2-cl4e), 29.06 (C¾a_5e), 24.84 (CH^), 22.68 (CH_2.ci_7e), 18.28 (CH_3-ma), 14.10 (CH_3-Ci8e).

HRMS (ESI): calcd for C28H4806H [M + H]+ 481.35237, found 481.35044

D-Isosorbide-2-Hexadecanoate-5-Methacrylate M3

Isosorbide 5 -methacrylate (1.285 g; 6 mmol) was dissolved in acetonitrile (10 mL), petroleum ether (10 mL) was added, followed by vinyl palmitate (3.39 g; 12 mmol) and Novozym 435 (0.2 g). The mixture was slowly stirred at 40-45°C for 120 hours. Then, the mixture was filtered and evaporated. Acetonitrile (40 mL) was added to the residue; after careful shaking the mixture was filtered and the solvent was evaporated.The product was purified by short column chromatography over silica gel (eluent: PE/EtOAc 10/0.5) to afford 2.159 g of the target compound (yield: 79.5%). H NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, ⁴J_HH=0.9 Hz, CH_2/ , 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, lH), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_4x, 1H), 4.48 (m, CH_3x,

1H), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH₂_ _2e, 2H), 1.96 (dd, ⁴J_HH=1.5 HZ, %_H=0.9 HZ, CH_3.ma, 3H), 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2.4.15e, 24H), 0.88 (t, ³J_HH = 7.1 Hz, CH_3.16e, 3H). ¹³C NMR (100.6 MHz, CDC1₃) d: 172.89 (COcie), 166.65 (CO_ma), 135.66 (C_ma), 126.30 (CH_2.ma), 86.05 (CH_C3), 80.88 (CH_2.C4), 77.81 (CH_2.C2), 74.11 (CH_C5), 73.46 (CH_2-CI), 70.61 (CH_C6), 34.16 (CH_2.C2e), 31.91 (CH_2.C3e), 29.65 (CH_2.C4e), 29.60-29.63 (CH_2.C5- 8e), 29.56 (CH_2.C9e), 29.41 (CH_2.Cio_e), 29.34 (CH_{2.Ci ie}), 29.21 (CH_2.Ci2e), 29.06 (CH_2.Ci3e), 24.84 (CH_2. C14e), 22.68 (CH_2-Ci5e), 18.28 (CH_3-ma), 14.10 (CH_3.Ci6e).

HRMS (ESI): calcd for C26H4406H [M + H]+ 453.32107, found 453.31887

D-Isosorbide-2-Tetradecanoate-5-Methacrylate M4

Obtained by the same method as Ml. Crude conversion 90%, isolated yield 55.7%.

Or this compound can also be synthesized as follows.

Isosorbide 5 -methacrylate (1.285 g; 6 mmol) was dissolved in acetonitrile (10 mL), petroleum ether (10 mL) was added followed by vinyl myristate (3.05 g; 3.51 mL; 12 mmol) and Novozym 435 (0.2 g). The mixture was stirred slowly at 40-45 °C for 120 hours. After that the mixture was filtered and the solvent was evaporated. Acetonitrile (40 mL) was added to the residue; after careful shaking the mixture was filtered and the sovent was evaporated. The product was purified by short column chromatography over silica gel (eluent: PE/EtOAc 10/0.5) to afford 2.105 g of the target compound (yield: 82.6%). ^lH NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, %_H=0.9 HZ, CH_2£, 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, 1H), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_2.4x, 1H), 4.48 (m, CH_3x, 1H), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH_2-2e, 2H), 1.96 (dd 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2-4_i_3e, 20H), 0.88

¹³C NMR (100.6 MHz, CDC1₃) d: 172.89 (CO ₄), 166.65 (CO_ma), 135.66 (C_ma), 126.30 (CH_2-ma), 86.05 (CH_C3), 80.88 (CH_2.C4), 77.81 (CH_2.C2), 74.11 (CH_C5), 73.46 (CH_2.CI), 70.61 (CH_C6), 34.16 (CH_2-C2e), 31.91 (CH_2.C3e), 29.65 (CH_2.C4e), 29.60-29.63 (CH_2.C5-6e), 29.56 (CH_2.c¾), 29.41 (CH_2.C8e), 29.34 (CH_2.C9e), 29.21 (CH_2.Cio_e), 29.06 (CH_{2.Ci ie}), 24.84 (CH_2.Ci2e), 22.68 (CH_2.Ci3e), 18.28 (CH_3-ma), 14.10 (CH₃_ci_4e).

HRMS (ESI): calcd for C24H40O6Na [M + Na]+ 447.27171, found 447.26947.

D-Isosorbide-2-Tridecanoate-5-Methacrylate M5

Obtained by same method as Ml. Crude conversion >90%, isolated yield 47.5% ^lU NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, %_H=0.9 HZ, CH_2£, 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, 1H), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_2.4x, 1H), 4.48 (m, CH_3x, 1H), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH_2.2e, 2H), 1.96 (dd, ⁴J_HH=1.5 Hz, %_H=0.9 HZ, CH_3.ma, 3H), 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2-4-12e, 18H), 0.86 (t, ³J_HH = 7.1 Hz, CH_3.13e, 3H).

¹³C NMR (100.6 MHz, CDC1₃) d: 172.89 (CO ₃), 166.65 (CO_ma), 135.66 (C_ma), 126.30 (CH_2.ma), 86.05 (CH_C3), 80.88 (CH_2.C4), 77.81 (CH_2.C2), 74.11 (CH_C5), 73.46 (CH_2.CI), 70.61 (CH_C6), 34.16 (CH_2-C2e), 31.91 (CH_2.C3e), 29.65 (CH_2.C4e), 29.47 (CH_2.C5e), 29.56 (CH_2.C6e), 29.41 (CH_2.C7e), 29.34 (CH_2.C8e), 29.21 (CH_2.C9e), 28.90 (CH_2.Cio_e), 24.68 (CH_{2.Ci ie}), 22.52 (CH_2.Ci2e), 18.13 (CH_3-ma), 13.94 (CH₃_ci_3e).

HRMS (ESI): calcd for C23H3806H [M + H]+ 411.27412, found 411.27488.

D-Isosorbide-2- Undecanoate-5-Methacrylate M6

Obtained by the same method as Ml. Crude conversion >90%, isolated yield 45.3%.

H NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, %H=0.9 HZ, CH_2/ , 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, lH), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_2-4x, 1H), 4.48 (m, CH_3x, lH), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH_2-2e, 2H), 1.96 (dd, ⁴J_HH=1.5 Hz, ⁴JHH=0.9 HZ, CH_3-ma, 3H), 1.59 (m, CH_2.3e, 2H), 1.23-1.26 (m, CH_2-4_ i0e, 14H), 0.88 (t, ³J_HH = 7.1 Hz, CH_3.Ue, 3H).

¹³C NMR (100.6 MHz, CDC1₃) d: 172.89 (CO_Cn), 166.65 (CO_ma), 135.66 (C_ma), 126.30 (CH_2.ma), 86.05 (CH_C3), 80.88 (CH_2.C4), 77.81 (CH_2.C2), 74.11 (CH_C5), 73.46 (CH_2.CI), 70.61 (CH_C6), 34.10 (CH_2-C2e), 31.80 (CH_2.C3e), 29.46 (CH_2.C4e), 29.35 (CH_2.C5e), 29.21 (CH_2.C6e), 29.14 (CH_2.C7e), 28.99 (CH_2.C8e), 24.77 (CH_2.C9e), 22.59 (CH_2.Cio_e), 18.21 (CH_3-ma), 14.02 (CH_3-Cn_e).

HRMS (ESI): calcd for C21H3406H [M + H]+ 383.24282, found 383.24246.

D-Isosorbide-2-Decanoate-5-Methacrylate M7

Isosorbide 5 -methacrylate (1.714 g; 8 mmol) was dissolved in acetonitrile (20 mL), vinyl decanoate (2.38 g; 2.7 ml; 12 mmol) and Novozym 435 (0.2 g) were added. After 48 h stirring at 40-45 °C an additional amount of vinyl decanoate (1.19 g; 1.35 mL; 6 mmol) was added. Stirring was continued for additional 48 hours, the completion of reaction was estimated by TLC. The enzyme was filtered off and the product was purified by flash chromatography over silica gel (eluent: PE/EtOAc 10/0.8) to afford 2.572 g of the target diester (yield: 87.2%). ^lU NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, ⁴J_HH=0.9 Hz, CH_2£, 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, 1H), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_2.4x, 1H), 4.48 (m, CH_3x, 1H), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH₂_ _2e, 2H), 1.96 (dd, ⁴J_HH=1.5 HZ, %_H=0.9 HZ, CH_3-ma, 3H), 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2-4-9e, 12H), 0.88 (t, ³J_HH = 7.1 Hz, CH_3.10e, 3H).¹³C NMR (100.6 MHz, CDC1₃) d: 172.87 (COcio), 166.61 (CO_ma), 135.61 (C_ma), 126.28 (CH_2.ma), 85.99 (CH_C3), 80.84 (CH_2.C4), 77.75 (CH_2.C2), 74.07 (CH_C5,), 73.41 (CH_2-O), 70.57 (CH_C6), 34.11 (CH_2.C2e), 33.82 (CH_2.C3e), 29.32 (CH_2.C4e), 29.18 (CH_2.C5e), 29.17 (CH_2.C6e), 29.01 (CH_2-C7e), 24.78 (CH_2.CSe), 22.60 (CH_2.C9e), 18.21 (CH_3-ma), 14.03 (CH_3.Cio_e)·

HRMS (ESI): calcd for C20H42O6H [M + H]+ 369.22717, found 369.22550

D-Isosorbide-2-Octanoate-5-Methacrylate M8

Isosorbide 5 -methacrylate (1.714 g; 8 mmol) was dissolved in acetonitrile (30 mL), triethylamine (1.42 g; 1.95 mL; 14 mmol) was added on stirring at RT followed by capryloyl chloride (1.334 g; 1.42 mL; 8.2 mmol).

The mixture was stirred at RT for 14 hours; methanol (64 mg; 0.081 ml; 2 mmol) was added and stirring was continued for an additional hour. Reaction mixture was evaporated, EtOAc (80 mL) added to the residue and the solution was washed with sat. NaHC0₃ and brine (both: 2x15 mL). The solution was dried over anhydrous Na₂S0₄, filtered and the solvent was evaporated. The product was purified by flash chromatography over silica gel (eluent: PE/EtOAc 10/1) to afford 2.552 g of the target diester (yield: 93.7%).

H NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, ⁴J_HH=0.9 Hz, CH_2/ , 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, lH), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_2-4x, 1H), 4.48 (m, CH_3x, 1H), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH₂_ _2e, 2H), 1.96 (dd, ⁴J_HH=1.5 HZ, ⁴J_HH=0.9 HZ, CH_3.ma, 3H), 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2-4-7e, 8H), 0.88 (t, ³JHH = 7.1 Hz, CH_3-8e, 3H).¹³C NMR (100.6 MHz, CDC1₃) d: 172.89 (CO_C8), 166.65 (CO ), 135.66 (C_ma), 126.30 (CH_2.ma), 86.05 (CH_C3), 80.88 (CH_2.C4), 77.81 (CH_2.C2), 74.11 (CH_C5, 1C), 73.46 (CH_2-CI), 70.61 (CH_C6), 34.14 (CH_2.C2e), 31.59 (CH_2.C3e), 28.99 (CH_2.C4e), 28.85 (CH_2.C5e, 1C), 24.81 (CH_2.C6e), 22.56 (CH_2.C7e), 18.28 (CH_3-ma), 14.02 (CH_3.C8e).

HRMS (ESI): calcd for C18H2806H [M + H]+ 341.19587, found 341.19524

D-Isosorbide-2-Hexanoate-5-Methacrylate M9

Isosorbide 5 -methacrylate (1.714; 8 mmol) was dissolved in acetonitrile (30 mL), triethylamine (1.42 g; 1.95 mL; 14 mmol) was added on stirring at RT followed by caproyl chloride (1.104 g; 1.14 mL; 8.2 mmol). The mixture was stirred at RT for 12 hours; the completion of reaction was estimated by TLC. Methanol (64.08 mg; 0.081 mL; 2 mmol) was added and stirring was continued for additional 2 hours. The reaction mixture was evaporated, EtOAc (80 mL) added to the residue and the solution washed with sat. NaHC0₃ (2x15 mL) and brine (2x15 mL). The solution was dried over anhydrous Na₂S04, filtered and the solvent was evaporated. The product was purified by flash chromatography over silica gel (eluent: PE/EtOAc 10/1.2) to afford 2.309 g of the target compound (y.: 92.4%).

H NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, ⁴J_HH=0.9 Hz, CH_2£, 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, 1H), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_2.4x, 1H), 4.48 (m, CH_3x, 1H), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH₂_ _2e, 2H), 1.96 (dd, ⁴J_HH=1.5 HZ, %_H=0.9 HZ, CH_3-ma, 3H), 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2-4-7e, 8H), 0.88 (t, ³J_HH = 7.1 Hz, CH_3-8e, 3H).¹³C NMR (100.6 MHz, CDC1₃) d: 172.91 (CO_C6), 166.66 (CO_ma), 135.64 (C_ma), 126.34 (CH_2.ma), 86.04 (CH_C3), 80.88 (CH_2.C4), 77.81 (CH_2.C2), 74.11 (CH_C5), 73.46 (CH_2-O), 70.61 (CH_C6), 34.15 (CH_2.C2e), 31.20 (CH_2.C3e), 24.51 (CH_2.C4e), 22.25 (CH_2.C5e), 18.30 (CH_3-ma), 13.87 (CH_3-C6e)· HRMS (ESI): calcd for C16H2406H [M + H]+ 313.16456, found 313.16440

D-Isosorbide-2-Butanoate-5-Methacrylate Ml 0

Isosorbide 5 -methacrylate (1.714 g; 8 mmol) was dissolved in acetonitrile (20 mL), triethylamine (1.42 g; 1.95 ml; 14 mmol) was added on stirring at RT, followed by butyryl chloride (1.28 g; 1.25 mL; 12 mmol). The mixture was stirred at RT for 12 hours; the completion of reaction was estimated by TLC. Methanol (0.2 mL; 5 mmol) was added and stirring was continued for additional 4 hours. Reaction mixture was evaporated, the residue was dissolved in EtOAc (80 mL) and washed with sat. NaHC0₃ (2x25 mL) and brine (2x15 mL). EtOAc solution was dried on anhydrous Na₂S04, filtered, hydroquinone (2 mg) was added and the solvent was evaporated. The product was purified by flash- chromatography (eluent PE/EtOAc 10/1.5) to afford homogeneous isosorbide 2-butyrate-5- methacrylate (2.177 g; yield: 95.7%). ^lH NMR (400 MHz, CDC1₃) d: 6.16 (dq, ²J_HH=1.5 Hz, ⁴J_HH=0.9 Hz, CH_2£, 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, 1H), 5.21 (m, CH_5x, 1H), 5.20 (m, CH_2n, 1H), 4.88 (m, CH_2.4x, 1H), 4.48 (m, CH_3x, 1H), 3.97 (m, CH_ln, 1H), 3.96 (m, CH_6x, 1H), 3.95 (m, CH_lx, 1H), 3.89 (m, CH_4n, 1H), 2.30 (m, CH₂_ _2e, 2H), 1.96 (dd, ⁴J_HH=1.5 HZ, %_H=0.9 HZ, CH_3-ma, 3H), 1.59 (m, CH_2-3e, 2H), 1.23-1.26 (m, CH_2-4-7e, 8H), 0.88 (t, ³J_HH = 7.1 Hz, CH_3-8e, 3H).¹³C NMR (100.6 MHz, CDC1₃) d: 172.70 (CO_C4), 166.64 (CO_ma), 135.64 (C_ma), 126.32 (CH_2.ma), 86.03 (CH_C3), 80.86 (CH_2.C4), 77.78 (CH_2.C2), 74.10 (CH_C5), 73.45 (CH_2-O), 70.61 (CH_C6), 35.98 (CH_2.C2e), 18.32 (CH_2.C3e, 18.27 (CH_3-ma), 13.56 (CH_3.C4e).

HRMS (ESI): calcd for C14H20O6H [M + H]+ 285.13326, found 285.13288

D-Isosorbide-2-(3, 4-dimethoxybenzoate)-5-Methacrylate Mil

Obtained by the same method as Ml. Isolated yield 41.2%, product was white crystals.

H NMR (400 MHz, CDC1₃) d: 7.63 (m, CH_arom, 1H), 7.47 (m, CH_arom, 1H), 6.85 (m, CH_arom, 1H), 6.16 (dq, ²J_HH=1.5 HZ, ⁴J_HH=0.9 HZ, CH_2/ , 1H), 5.62 (dd, ²J_HH=1.5 Hz, ⁴J_HH= 1.5, CH_2Z, 1H), 5.42 (m, CH_2n, 1H), 5.21 (m, CH_5x, 1H), 4.96 (m, CH_2-4x, 1H), 4.62 (m, CH_3x, 1H), 4.02 (m, CH_ln, 1H), 4.01 (m, CH_6x, lH), 3.96 (m, CH_lx, 1H), 3.92 (m, CH_4n, 1H), 3.91 (s, OCH_3.arom, 3H), 3.90 (s, OCH_3.arom), 1.96 (dd, ⁴J_HH=1.5 HZ, ⁴J_HH=0.9 HZ, CH_3.ma, 3H). ¹³C NMR (100.6 MHz, CDC1₃) d: 166.65 (CO_ma), 166.30 (CO_Cbenz), 153.52 (C_arom), 148.63 (C_arom), 135.66 (C_ma), 126.30 (CH_2.ma), 123.83(C_arom), 121.82 (C_arom), 110.90 (C_arom), 110.18 (C_arom), 86.07 (CH_C3), 80.89 (CH_2.C4), 78.27 (CH_2.C2), 74.17 (CH_C5), 73.37 (CH_2.CI), 70.56 (CH_C6), 55.98 (OCH₃), 55.96 (OCH₃), 18.21 (CH_3-ma). HRMS (ESI): calcd for C19H2202H [M + H]+ 379.13874, found 379.13888.

D-Isosorbide-5-Octadecanoate-2-Methacrylate M12

Obtained by the same method as Ml. Crude conversion >90%, reaction gave white crystals (yield 49.2%). H NMR (400 MHz, CDC1₃) d: 6.07 (dq, ²J_HH=1.5 Hz, ⁴J_HH=0.9 Hz, CH_2/l, 1H), 5.56 (dd, ²J_HH=1.5 Hz, ⁴J_hh= 1.5, CH_2Z, lH), 5.21 (m, CH_2n, 1H), 5.1 l(m, CH_5x, 1H), 4.82 (m, CH_4x, 1H), 4.49 (m, CH_3x,

1H), 3.97 (m, CH_lx, 1H), 3.96 (m, CH_ln, 1H), 3.91 (m, CH_6x, 1H), 3.78 (m, CH_6n, 1H), 2.32 (m, CH₂_ _2e, 2H), 1.88 (dd, ⁴J_HH=1.5 HZ, %_H=0.9 HZ, CH_3.ma, 3H), 1.60 (m, CH_2-3e, 2H), 1.20-1.23 (m, CH_2-4-17e, 18H), 0.83 (t, ³JHH^— 7.1 Hz, CH₃_i_8e, 3H). ¹³C NMR (100.6 MHz, CDC1₃) d: 173.06 (COcis, 1C), 166.16 (CO_ma), 135.58 (C_ma), 126.35 (CH_2.ma),

85.79 (CH_C3), 80.64 (CH_C4), 78.14 (CH_C2), 73.66 (CH_C5), 73.23 (CH_2.CI), 70.21 (CH_2.C6), 33.82 (CH_{2. C2e}), 31.81 (CH_2.C3e), 29.5-29.6 (CH_2.C4-io_e), 29.45 (CH_{2.Ci ie}), 29.33 (CH_2.Ci2e), 29.25 (CH_2.Ci3e), 29.14 (CH_2.ci_4e), 28.95(CH₂_ci5e), 24.76 (CH_2.Ci6e), 22.57 (CH_2.Ci7e), 18.03 (CH_3-ma), 14.06 (CH_3.Ci8e).

HRMS (ESI): calcd for C28H4806H [M + H]+ 481.35237, found 481.35073.

Synthesis of monomethacrylic isosorbide polymers.

General procedure for free radical polymerization of isosorbide-based monomethacrylates. Isosorbide mono -methacrylate (1-7; 270-350 mg) was filtered through basic AI₂O₃ to remove the stabilizer (hydroquinone) and placed into a 8 mL pressure tube. Then EtOAc (2.7-3.5 mL) and AIBN (0.5, 0.25, 0.13, or 0.06 mol%) dissolved in EtOAc was added (DMSO was used instead of EtOAc for monomers 1 and 2). After sparging the mixture with Ar for 45 min, the tube was sealed firmly with a cap and placed into a preheated oven at 60 °C for 24 h. The reaction was then cooled down to room temperature and a small sample was taken to determine the conversion of the monomer by 1H NMR. The crude product was precipitated into an appropriate solvent (MeOH, Et₂0, or the mixture of Et₂0 and iso- propanol) to remove any residual monomer and filtrated from the same solvent three times. After filtration a solid product was collected and carefully dried in vacuum. For the dried product NMR, SEC, DSC, TGA, and intrinsic viscosity measurements were carried out.

Polymer of D-Isosorbide-2-Eicosanoate-5-Methacrylate PI

Monomer Ml (230 mg, 0.45 mmol) and A1BN (0.37 mg, 0.0023 mmol, 0.5 mol%) were dissolved in toluene (2.3 mL). Solution was deoxygenized with argon gas for 1 hour. Mixture was put into the pre- heated oven for 24 hours. Polymerization was checked by NMR. The crude polymer was precipitated in methanol (100 mL) and left stirring for overnight. The precipitation was filtered, washed with additional amount of methanol and dried under reduced pressure. Conversion 70%, average molecular weight 43 kg/mol (PD1 = 2.84).T_{d (95o/)}259 °C, T_m 59 and 85 °C, T_c 49 and 80°C. ^lH NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2-2e), 1.59

(bm, CH_2-3e), 1.30 (bm, CH_3-ma), 1.21-1.28 (bm, CH_2.4.19e), 0.87 (bm, CH_3-20e).

Polymer of D-Isosorbide-5-Octadecanoate-2-Methacrylate P12

Monomer M12 (180 mg, 0.37 mmol) and A1BN (0.31 mg, 0.0019 mmol, 0.5 mol%) dissolved in ethylacetate (1.8 mL). Solution was deoxygenized with argon gas for 1 hour. Mixture was put into the pre-heated oven for 24 hours. Polymerization was checked by NMR. The crude polymer was precipitated in methanol (100 mL) and left stirring for overnight. The precipitation was filtered, washed with additional amount of methanol and dried under reduced pressure. Conversion 58%, number average molecular weight 49 kg/mol (PD1 = 2.1). T_{d (95o/o)}25l °C, T_m 30 °C, T_c 23 °C. ^lH NMR (400 MHz, CDC1₃) d: 5.21 (bm, CH_2n), 5.04 (bm, CH_5x), 4.86 (bm, CH_4x), 4.51 (bm,

CH_3x), 3.97 (bm, CH_lx), 3.94 (bm, CH_ln), 3.92 (bm, CH_6x), 3.82 (bm, CH_6n), 2.39 (bm, CH_2-2e), 1.66 (bm, CH_2-3e), 1.30 (bm, CH_3-ma), 1.21-1.30 (bm, CH_2-4_i_7e), 0.91 (bm, CH₃_i_8e). Polymer of D-Isosorbide-2-Octadecanoate-5-Methacrylate P2

Polymer P2 was made of monomer M2 by the same procedure as polymer P12. Conversion 56%, number average molecular weight 31 kg/mol (PDI = 1.8). T_{d (95o/)} 254 °C, T_m 40 and 93 °C, T_c 34 and 85 °C.

Polymer of D-Isosorbide-2-Hexadecanoate-5-Methacrylate P3

Polymer P3 was made of monomer M3 by the same procedure as polymer P12. Conversion 82%, number average molecular weight 58 kg/mol (PDI = 2.1). T_{d (95o/o)} 231 °C, T_m 16 and 86 °C, T_c 12 and 79 °C. H NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2-2e), 1.59 (bm, CH_2.3e), 1.30 (bm, CH_3-ma), 1.21-1.28 (bm, CH_2.4.15e), 0.87 (bm, CH_3-16e).

Polymer of D-Isosorbide-2-Tetradecanoate-5-Methacrylate P4 Polymer P4 was made of monomer M4 by the same procedure as polymer P12. Conversion 82%, number average molecular weight 51 kg/mol (PDI = 2.2). T_{d (95o/)} 233 °C, T_m -4 and 82 °C, T_c -10 and 73 °C. ^lH NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2-2e), 1.59 (bm, CH_2.3e), 1.30 (bm, CH_3-ma), 1.21-1.28 (bm, CH_2.4.13e), 0.87 (bm, CH_3.14e).

Polymer of D-Isosorbide-2-Tridecanoate-5-Methacrylate P5

Polymer P5 was made of monomer M5 by the same procedure as polymer P12. Conversion 81%, number average molecular weight 32 kg/mol (PDI = 2.3). T_{d (95o/o)} 228 °C, T_m 75 °C, T_c 65 °C. H NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2-2e), 1.59 (bm, CH_2-3e), 1.30 (bm, CH_3.ma), 1.21-1.28 (bm, CH_2.4.12e), 0.87 (bm, CH_3.13e).

Polymer of D-Isosorbide-2-Undecanoate-5-Methacrylate P6

Polymer P6 was made of monomer M6 by the same procedure as polymer P12. Conversion 79%, number average molecular weight 56 kg/mol (PDI = 2.2). T_{d (95o/o)} 209 °C, T_g 56 °C. ^lH NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2-2e), 1.59 (bm, CH_2.3e), 1.30 (bm, CH_3-ma), 1.21-1.28 (bm, CH_2.4.10e), 0.87 (bm, CH_{3.l le}).

Polymer of D-Isosorbide-2-Decanoate-5-Methacrylate P7

Polymer P7 was made of monomer M7 by the same procedure as polymer P12. Conversion 56%, number average molecular weight 47 kg/mol (PDI = 1.8). T_{d (95o/o)} 201 °C, T_g 52 °C.

H NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2-2e), 1.59 (bm, CH_2-3e), 1.30 (bm, CH_3.ma), 1.28-1.34 (bm, CH_2.4.9e), 0.88 (bm, CH_3.i0e).

Polymer of D-Isosorbide-2-Octanoate-5-Methacrylate P8

Polymer P8 was made of monomer M8 by the same procedure as polymer P12. Conversion 76%, number average molecular weight 38 kg/mol (PDI = 2.2) T_{d (95%)} 199 °C, T_g 46 °C.

H NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2.2e), 1.59 (bm, CH_2.3e), 1.30 (bm, CH_3.ma), 1.28-1.34 (bm, CH_2-4-7e), 0.88 (bm, CH_3-8e). Polymer of D-Isosorbide-2-Hexanoate-5-Methacrylate P9

Polymer P9 was made of monomer M9 by the same procedure as polymer P12. Conversion 63%, number average molecular weight 54 kg/mol (PDI = 2.1). T_{d (95%)} 188 °C, T_g 57 °C. ^lH NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2-2e), 1.59 (bm, CH_2-3e), 1.30 (bm, CH_3-ma), 1.26-1.25 (bm, CH_2.4.5e), 0.89 (bm, CH_3-6e).

Polymer of D-Isosorbide-2-Butanoate-5-Methacrylate P10 Polymer P10 was made of monomer M10 by the same procedure as polymer P12. Conversion 67%, number average molecular weight 38 kg/mol (PDI = 2.1).

H NMR (400 MHz, CDC1₃) d: 5.27 (bm, CH_5x), 4.99 (bm, CH_2n), 4.72 (bm, CH_4x), 4.46 (bm, CH_3x), 3.95 (bm, CH_ln), 3.94 (bm, CH_6x), 3.92 (bm, CH_lx), 3.73 (bm, CH_4n), 2.30 (bm, CH_2-2e), 1.59 (bm, CH_2-3e), 1.30 (bm, CH_3-ma), 0.99 (bm, CH_3-4e).

Polymer of D-Isosorbide-2-(3, 4-dimethoxybenzoate)-5-Methacrylate Pll

Polymer Pll was made of monomer Mil by the same procedure as polymer P12. Conversion 33%, number average molecular weight 31 kg/mol (PDI = 1.5). T_{d (95%)}236 °C, T_g 106 °C. ^lH NMR (400 MHz, CDC1₃) d: 7.56, 7.41, 6.79, 5.36, 5.02, 4.82, 4.55, 4.10, 3.85, 1.10.

Polymer of D-Isosorbide-2-Octadecanoate-5-Methacrylate and D-Isosorbide-5-Octadecanoate-2- Methacrylate PI 3

Monomers M2 and M12 (252 mg, ratio 1 :1, 0.52 mmol) dissolved in ethylacetate (2.52 mL). Added AIBN (0.43 mg, 0.0023 mmol). Solution was deoxygenized with argon gas for 1 hour. Mixture was put into the pre-heated oven for 24 hours. Polymerization was checked by NMR. The crude polymer was precipitated in methanol (100 mL) and left stirring for overnight. The precipitation was filtered, washed with additional amount of methanol and dried under reduced pressure. Conversion 75%, average molecular weight 81 kg/mol (PDI = 2.1). T_{d (95o/)} 247 °C, T_m 41 and 69 °C, T_c 35 and 59 °C. ^lU NMR (400 MHz, CDC1₃) d: 5.30; 5.18, 5.01, 4.72, 4.46, 3.9-4.0, 3.73-3.77, 2.30-2.35, 1.60, 1.30 (CH_3.ma), 1.20-1.35 (CH_2.4-I8), 0.87 (CH_3-18)

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Supporting Information Section

Evaluation of the solubility of isosorbide polymethacrylates. The solubility of the different isosorbide polymethacrylates was investigated by mixing small samples (about 5 mg) with a range of selected solvents (1 mL). The mixture was stirred for 24 h at room temperature. The results of the dissolution tests were divided into two categories, soluble and insoluble, based on visual inspection. If the samples were found to be completely dissolved, they were considered as soluble; if not, they were considered as nonsoluble.

Table S2: Solubility of the isosorbide polymethacrylates at 21 °C. solvent⁰

Polymer film preparation. About 50 mg of the isosorbide polymethacrylate nr was dissolved in 2 m 1. of DMSO. The solution was then poured onto a Teflon Petri dish (d = 30 mm) and casting was done overnight on a hotplate at 30 °C. The polymethacrylates of isosorbide formed transparent films. Preferred embodiments of the invention are defined in the clauses below:

1. A method for the enzymatic regiospecific synthesis of D-isosorbide 5 -methacrylate in an organic solvent, comprizing of the following steps:

a) D-isosorbide is incubated with a methacryl donor together with the enzyme in an organic lipophilic solvent, thereafter

b) The enzyme is eliminated from the reaction mixture, and

c) The reaction mixture is evaporated and the crude product is dissolved in ethyl acetate, and d) Is washed with NaHC03 water solution in order to eliminate the methacrylic acid formed in the reaction environment, thereafter

e) The product is washed with brine, dried and evaporated, and thereafter

f) The product is dissolved in ethanol, activated charcoal is added, the mixture is stirred for 12 hours, filtered and evaporated to afford target D-isosorbide 5 -methacrylate of high quality. 2. A method for the synthesis of D-isosorbide 5 -methacrylate in accordance with the point 1, differing by the circumstance that methacryl donor is vinyl methacrylate.

3. A method for the synthesis of D-isosorbide 5 -methacrylate in accordance with the point 1, differing by the circumstance that methacryl donor is methacrylic anhydride.

4. A method for the synthesis of D-isosorbide 5 -methacrylate in accordance with the point 2, that differs by the circumstance that in the step a) D-isosorbide is incubated with vinyl methacrylate and the enzyme in an organic lipopfilic solvent at the temperature of l5-25°C during 60 hours up to the conversion of 90-95%.

5. A method for the synthesis of D-isosorbide 5 -methacrylate in accordance with the point 3, that differs by the circumstance that in the step a) D-isosorbide is incubated with methacrylic anhydride and the enzyme in an organic lipophilic solvent at temperature of l5-25°C during 40 hours up to the conversion of 90-95% after which the excess of methacrylic anhydride is destroyed.

6. A method for the synthesis of D-isosorbide 5 -methacrylate in accordance with the point 1, that differs by the circumstance that the enzyme used is Rhizomucor miehei lipase

(Lipozyme®RM IM).

7. A method for the synthesis of D-isosorbide 5 -methacrylate in accordance with the point 1, differing by the circumstance that the organic lipophilic solvent is methyl tert-butyl ether.

8. A method for the synthesis of D-isosorbide 5 -methacrylate in accordance with the point 5, differing by the circumstance that water is added to the solution in order to destroy methacrylic anhydride by the enzyme present in the mixture.

9. D-isosorbide 5 -methacrylate, synthesized in an environment of organic solvent using the regiospecific enzymatic method that accords to points 1-8, corresponds to the purity level of 95% or higher and is obtained with the yield of 74% or higher.

10. D-isosorbide 5-methacrylate, synthesized in an environment of organic solvent using the regiospecific enzymatic method that accords to points 1-8, corresponds to the purity level of up to 99% and is obtained with the yield of 87% or higher. A preferred embodiment of the present invention is the regiospecific enzymatic synthesis of D- isosorbide 5 -methacrylate in two different modifications, which use different acyl donors, correspondingly, 1) vinyl methacrylate and 2) methacrylic anhydride and the catalyst in both cases is Rhizomucor miehei lipozyme (Lipozym® RM IM), whereas the solvent is methyl tert- butyl ether. Isosorbide is incubated with the lipozyme and substrate. Then the enzyme is filtrated and the filtrate is washed with saturated sodium hydrogen carbonate and brine in order to eliminate methacrylic acid formed in the reaction medium and also, to remove unreacted isosorbide. The resulting solution is dried, filtered and evaporated. The crude product is then dissolved in ethanol, activated charcoal is added and the mixture is stirred, followed by the filtration and evaporation of the solution. As a result, isosorbide 5 -methacrylate is obtained with over 99% purity (95% in case of the other method) and

87% (74%) yield.

All optional and preferred features and modifications of the described embodiments and dependent claims are usable in all aspects of the invention taught herein. Furthermore, the individual features of the dependent claims, as well as all optional and preferred features and modifications of the described embodiments are combinable and interchangeable with one another.

The disclosures in UK patent application numbers 1806402.2 and 1807794.1, from which this application claims priority, and in the abstract accompanying this application are incorporated herein by reference.

Claims

1. A method of preparing isosorbide 5-methacrylate including the steps of reacting isosorbide with a methacryl donor in the presence of Rhizomucor miehei lipase.

2. A method as claimed in claim 1, wherein the methacryl donor is vinyl methacrylate, methacrylic anhydride, or a combination thereof.

3. A method as claimed in any preceding claim, wherein the reaction takes place in the presence of an organic solvent.

4. A method as claimed in any preceding claim, wherein the reaction takes place in the presence of methyl tert-butyl ether.

5. A method as claimed in any preceding claim, wherein the reaction takes place at a temperature from l5°C to 25°C.

6. A method of preparing an isosorbide 5-methacrylate diester, including the steps of carrying out a method as claimed in any preceding claim to prepare isosorbide 5-methacrylate and then reacting the hydroxyl group at the 2-position of the isosorbide 5-methacrylate with a compound having an acyl group.

7. A method as claimed in claim 6, wherein the compound having an acyl group is acetic anhydride, vinyl laurate or cyclohexanecarbonyl chloride.

8. An isosorbide 5-methacrylate diester obtainable by means of a method as claimed in claim 6 or 7.

9. An isosorbide 5-methacrylate diester having the formula shown in compounds 3, 5 and 7 below:

Conditions: 3: acetic anydride, Et₃N, ACN, rt

5: vinyl laurate, Novozym 435, MTBE, rt

7: cyclohexanecarbonyl chloride, ACN/pyridine, rt

10. A method of preparing isosorbide 2-methacrylate including the steps of:

(a) reacting isosorbide with a compound which includes a protecting group having acyl functionality in the presence of Rhizomucor miehei lipase in order to produce an isosorbide with a protecting group at the 5-position,

(b) reacting the product of step (a) with a methacrylate donor in order to produce an isosorbide 2-methacrylate with a protecting group at the 5-position, and

(c) hydrolysing the product of step (b) in order to remove the protecting group and form isosorbide 2-methacrylate.

11. A method as claimed in claim 10 wherein said compound in step (a) is vinyl acetate or vinyl laurate.

12. A method as claimed in claim 10 or 11 wherein the methacryl donor of step (b) is vinyl methacrylate, methacrylic anhydride, or a combination thereof.

13. A method as claimed in any of claims 10 to 12, wherein Novozym 435 is used to catalyse step

(c)·

14. A method of preparing isosorbide 2-methacrylate-5-acetate or isosorbide 2-methacrylate-5- laurate including the steps of:

(a) reacting isosorbide with either vinyl acetate or vinyl laurate in the presence of Rhizomucor miehei lipase in order to produce an isosorbide-5-acetate or isosorbide-5-laurate, and (b) reacting the product of step (a) with a methacryl donor in order to produce isosorbide 2- methacrylate-5-acetate or 2-methacrylate-5-laurate.

15. Isosorbide 2-methacrylate-5 -acetate or isosorbide 2-methacrylate-5-laurate obtainable by means of a method as claimed in claim 14.

16. Isosorbide 2-methacrylate-5-laurate.

17. A method of preparing a polymer including the steps of preparing a monomer as claimed in any of claims 1-5, 6-7, 10-13 or 14, and then carrying out a polymerisation of said monomer with itself or of a mixture of two or more of said monomers or with any other monomer to produce a copolymer.

18. A method of preparing a polymer including carrying out a polymerisation of a monomer as claimed in any of claims 8, 9, 15 or 16 with itself or of a mixture of two or more of said monomers or with any other monomer to produce a copolymer.

19. A method as claimed in claim 17 or 18, wherein the polymerisation is a free radical

polymerisation.

20. A method as claimed in claim 19, wherein the free radical polymerisation is initiated by using

UV light, redox initiators, thermal initiators, hydrogen peroxide or A1BN.

21. A polymer obtainable by means of carrying out a method as claimed in any of claims 17 to

20.

22. A polymer having the formula shown in compounds 11, 12, 15, 16 or 17 below:

23. A polymer having the formula shown below:

wherein R is -(CH₂)_mCH3 with m being any whole number from 0 to 18;

or R is a phenyl group substituted with from 1 to 5 substituents which are independently H,

OH, an alkoxyl group or an alkyl group.

24. A polymer having the formula shown below:

wherein R is -(CH₂)_mCH3 with m being any whole number from 0 to 18.

25. A polymer as claimed in any of claims 21 to 24 in combination with a thermoplastic elastomer.

26. A coating comprising a monomer as claimed in any of claims 8, 9, 15 or 16.