One-Pot FDCA Diester Synthesis from Mucic Acid and Their Solvent-Free Regioselective Polytransesteriﬁcation for Production of Glycerol-Based Furanic Polyesters

molecules

Article One-Pot FDCA Diester Synthesis from Mucic Acid and Their Solvent-Free Regioselective Polytransesteriﬁcation for Production of Glycerol-Based Furanic Polyesters

Deyang Zhao 1,2, Frederic Delbecq 3 and Christophe Len 1,2,*

1 Sorbonne Universités, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, F-60203 Compiègne CEDEX, France; [email protected] 2 PSL Research University, Chimie ParisTech, CNRS, Institute of Chemistry for Life and Health Sciences, 11 rue Pierre et Marie Curie, F-75231 Paris CEDEX 05, France 3 Ecole Supérieure de Chimie Organique et Minérale, 1 allée du Réseau Jean-Marie Buckmaster, F-60200 Compiègne, France; [email protected] * Correspondence: [email protected]; Tel.: +33-(0)638-500-976; Fax: +33-(0)344-971-591

Received: 17 February 2019; Accepted: 8 March 2019; Published: 15 March 2019

Abstract: A one pot-two step procedure for the synthesis of diethyl furan-2,5-dicarboxylate (DEFDC) starting from mucic acid without isolation of the intermediate furan dicarboxylic acid (FDCA) was studied. Then, the production of three different kinds of furan-based polyesters— polyethylene-2,5-furan dicarboxylate (PEF), polyhydropropyl-2,5-furan dicarboxylate(PHPF) and polydiglycerol-2,5-furandicarboxylate (PDGF)—was realized through a Co(Ac)2·4H2O catalyzed polytransesterification performed at 160 ◦C between DEFDC and a defined diol furan-based prepolymer or pure diglycerol. In parallel to polymerization process, an unattended regioselective 1-OH acylation of glycerol by direct microwave-heated FDCA diester transesterification led to the formation of a symmetric prepolymer ready for further polymerization and clearly identified by 2D NMR sequences. Furthermore, the synthesis of a more soluble and hydrophilic diglycerol-based furanic polyester was also achieved. The resulting biobased polymers were characterized by NMR, FT-IR spectroscopy, DSC, TGA and XRD. The morphologies of the resulted polymers were observed by FE-SEM and the purity of the material by EDX.

Keywords: mucic acid dehydration; FDCA diesters; regioselective transesterification; poly-transesterification

1. Introduction Furandicarboxylic acid (FDCA) is recognized as one of the twelve building-block chemicals by the US Department of Energy. This aromatic compound is easily synthesized through the dehydration of fructose to hydroxymethylfurfural (HMF) under acidic conditions and then peroxidation using various oxidants in one-pot one-step and one-pot two-step reactions (Scheme1)[ 1–4]. The direct conversion of HMF to FDCA is technically feasible, but faces problems of cost, stability and availability. Catalytic oxidation of HMF to FDCA using homogeneous catalysis was reported but these processes were less attractive as compared with heterogeneous catalysis due to the separation and recycling problems [5–7]. Modern heterogeneous catalysts such as nanosized bimetallic catalysts could also become a good alternative for the FDCA production [5,8–10]. Using homogeneous catalyst or heterogeneous catalyst the main limitation of the process remains the cost of HMF itself. In fact, this furanic intermediate is industrially produced in moderate yields by the dehydration of hexoses (fructose and glucose) isolated as sub-units from the depolymerization of polysaccharides such as

Molecules 2019, 24, 1030; doi:10.3390/molecules24061030 www.mdpi.com/journal/molecules Molecules 2019, 24, x FOR PEER REVIEW 2 of 15 Molecules 2019, 24, 1030 2 of 15 In fact, this furanic intermediate is industrially produced in moderate yields by the dehydration of hexoses (fructose and glucose) isolated as sub-units from the depolymerization of polysaccharides cellulose or starch [11,12]. Nowadays, it appears important to ﬁnd more efﬁcient pathway to access such as cellulose or starch [11,12]. Nowadays, it appears important to find more efficient pathway to FDCA analogs. One of the most promising routes should be the dehydration of mucic acid in the access FDCA analogs. One of the most promising routes should be the dehydration of mucic acid in presence of strong mineral acid (H2SO4,H3PO4, HBr) [13] or para-toluenesulfonic acid (PTSA) [14]. the presence of strong mineral acid (H2SO4, H3PO4, HBr) [13] or para-toluenesulfonic acid (PTSA) Mucic acid offers the advantage of having two carboxylic acid groups. [14]. Mucic acid offers the advantage of having two carboxylic acid groups.

SchemeScheme 1.1.Different Different ways ways for thefor production the production of 2,5-furandicarboxylic of 2,5-furandicarboxylic acid starting acid from lignocellulose.starting from lignocellulose. FDCA is often employed as one of the components for the preparation of linear or branched polyestersFDCA showing is often relevantemployed thermal as one and of mechanicalthe componen propertiests for the [15 preparation]. FDCA polyesters of linear express or branched good biocompatibilitypolyesters showing with relevant the human thermal body. and Thesemechanical polymers properties are expected [15]. FDCA to be polyesters useful in aexpress near future good inbiocompatibility the field of commodity with the thermoplastichuman body. These engineering polymers polymers are expected like the to well-exploited be useful in a near polyethylene future in terephthalatethe field of commodity (PET). More thermoplastic exactly, FDCA engineering is used to polymers replace the likep-terephthalic the well-exploited acid (PTA), polyethylene which is overallterephthalate an oxidation (PET). More product exactly, of p-xylene, FDCA anis used aromatic to replace compound the p-terephthalic issued from acid refined (PTA), oil. which Besides, is PEToverall is mainly an oxidation composed product of two of Y-X-Yp-xylene, type an monomers: aromatic compound PTA and ethylene issued glycolfrom refined (EG). In oil. case Besides, of EG, thisPET diolis mainly is now composed a biobased of buildingtwo Y-X-Y block type generated monomers: by PTA the biochemical and ethylene transformation glycol (EG). In of case D-xylose. of EG, Thethis polymerizationdiol is now a biobased of FDCA building or its counterparts block generated with by EG the is alreadybiochemical set up transformation in industry for of producing D-xylose. polyethylene-2,5-furanThe polymerization of FDCA dicarboxylate or its counterparts (PEF) for commercialwith EG is already applications set up suchin industry as beverage for producing bottles. Frompolyethylene-2,5-furan a physicochemical dicarboxylate point of view (PEF) PEF isfor a polyestercommercial of higherapplications glass transitionsuch as beverage and structurally bottles. ◦ lessFrom linear a physicochemical than PET due point to the of angle view ofPEF 129 is aformed polyester between of higher the glass two consecutivetransition and ester structurally function holdless linear by the than furan PET rings. due Onto the the angle other of hand, 129° form fromed a technicalbetween the point two of consecutive view, except ester the veryfunction classical hold meltingby the furan polycondensation rings. On the of other FDCA hand, mixed from with a ate diolchnical [16 ],point to access of view, to these except polymers the very the classical furanic diacidmelting need polycondensation to be activated of leadingFDCA mixed to the with formation a diol of[16], its to corresponding access to these furan-2,5-dicarboxylic polymers the furanic aciddiacid dichloride need to be (FDCC) activated [17 leading,18], but to the the process formation requires of its corresponding hazardous chlorination furan-2,5-dicarboxylic reagents such acid as phosphorousdichloride (FDCC) pentachloride [17,18], orbut thionyl the process chloride. requir Oncees hazardous the diacyl chlorination chloride derivative reagents is such formed, as itphosphorous could react withpentachloride various diolsor thionyl or diamines chloride. to formOnce theirthe diacyl respective chloride polyesters derivative and is polyamides, formed, it butcould the react main with problem various of FDCCdiols or accessibility diamines to is causedform their by therespective low solubility polyesters of FDCA and polyamides, in the common but organicthe main solvents. problem Inof comparison,FDCC accessibility the diesters is caused of FDCA by the are low easier solubility to handle of FDCA and far in morethe common soluble andorganic could solvents. react withIn comparison, various diols the diesters in presence of FDCA of catalysts are easier such to handle as tetraalkyl and far more titanates soluble [19– and21], tincould (II) react 2-ethylhexanoate with various [22diols,23 ],in antimony presence trioxideof catalysts (III) such [24–30 as] buttetraalkyl always titanates active at [19–21], temperatures tin (II) superior2-ethylhexanoate to 200 ◦C. [22,23], A recent antimony paper reported trioxide the(III) use [24–30] of 1,8-diazabicyclo but always active [5.4.0]undec-7-ene at temperatures (DBU) superior as anto organocatalyst200 °C. A recent to performpaper reported the polytransesterification the use of 1,8-diazabicyclo of FDCA [5.4.0]undec-7-ene dimethyl ester (DMFDC) (DBU) inas thean presenceorganocatalyst of EG [to31 ].perform Another the strategy polytransesterific to synthesizeation PEF involvesof FDCA the dimethyl polymerization ester (DMFDC) of a prepolymer in the namedpresence bis(hydroxyethyl)-2,5-furandicarboxylate of EG [31]. Another strategy to synt (BHEFDC)hesize PEF [32]. Thisinvolves material the ispolymerization obtained by reaction of a

Molecules 2019, 24, x FOR PEER REVIEW 3 of 15 prepolymer named bis(hydroxyethyl)-2,5-furandicarboxylate (BHEFDC) [32]. This material is Molecules 2019, 24, 1030 3 of 15 obtained by reaction of DMFDC immersed in a large excess of EG and heated at temperatures between 160 and 220 °C. The following polymerization must be carried out under reduced pressure toof DMFDCremove the immersed released in EG a large by-product. excess of This EG andkindheated of procedure at temperatures is genera betweenlly a source 160 andof possible 220 ◦C. degradationThe following of polymerization the product and must an beenergy carried consuming out under process. reduced pressureGenerally, to removethe solid the polymers released are EG obtainedby-product. as dark This brown kind of solids procedure only issoluble generally in halogenated a source of possiblesolvents degradationsuch as trifluoacetic of the product acid (TFA) and oran tetrachloroethane. energy consuming process. Generally, the solid polymers are obtained as dark brown solids only solubleThe in first halogenated objective solventsof this present such as work trifluoacetic was to acid define (TFA) greener or tetrachloroethane. reaction conditions to rapidly produceThe FDCA first objective diethyl ofester this from present mucic work acid was in toethanol, define its greener transformation reaction conditions via metal-catalyzed to rapidly transesterificationproduce FDCA diethyl into prepolymer ester from counterparts mucic acid in using ethanol, three its really transformation different polyols via metal-catalyzed (EG, glycerol andtransesterification α,α-diglycerol). into Each prepolymer prepolymer counterparts was allowed using to re threeact with really one different equivalent polyols of the (EG, FDCA glycerol diester and inα, αthe-diglycerol). presence Eachof cobalt prepolymer (II) acetate was allowed to gene torate react at with a moderate one equivalent temperature of the FDCA the target diester linear in the polymers.presence ofAll cobalt compounds (II) acetate and tomaterials generate reported at a moderate in this present temperature paper were the target studied linear by NMR polymers. and FT-IRAll compounds spectroscopies. and materialsThe polymeric reported materials in this were present characterized paper were by XRD, studied TGA by and NMR DSC and analysis FT-IR andspectroscopies. the morphology The polymeric of the solid materials were observed were characterized by FE-SEM. by XRD, TGA and DSC analysis and the morphology of the solid were observed by FE-SEM. 2. Results and Discussion 2. Results and Discussion In order to produce the furanic polyesters, a simple synthetic route was set up starting from mucicIn acid order (Scheme to produce 2). The the main furanic ch polyesters,allenge remains a simple the syntheticchoice of routemucic was acid set as up the starting exclusive from starting mucic materialacid (Scheme for 2the). The production main challenge of furanic remains polyesters. the choice In of order mucic to acid achieve as the exclusivethe polymerizations, starting material this methodfor the production required the of furanicpreparation polyesters. of prepolymers In order to th achieverough thesolvent-free polymerizations, transesterifications this method between required thethe preparationproduced diethyl of prepolymers furan-2,5-dicarboxylate through solvent-free (DEF transesterificationsDC) and a chosen betweenpolyol in the the produced presence diethyl of a transitionfuran-2,5-dicarboxylate metal diacetate. (DEFDC) and a chosen polyol in the presence of a transition metal diacetate.

SchemeScheme 2. 2. EntireEntire synthetic synthetic routes routes to to linear linear fu furanicranic polyesters from mucic acid.

2.1. Optimization of DEFDC Synthesis 2.1. Optimization of DEFDC Synthesis For the purpose of carbon economy, the transformation of mucic acid into diethyl ester DEFDC For the purpose of carbon economy, the transformation of mucic acid into diethyl ester DEFDC was carried out in the presence of PTSA (4 equivalents) as acid catalyst in ethanol at 160 ◦C for was carried out in the presence of PTSA (4 equivalents) as acid catalyst in ethanol at 160 °C for 1 h. 1 h. However, despite our efforts using a one-pot two-step procedure (formation of FDCA and However, despite our efforts using a one-pot two-step procedure (formation of FDCA and then then formation of the diester), only traces of the target diester DEFDC was obtained due to the low formation of the diester), only traces of the target diester DEFDC was obtained due to the low formation of FDCA. In this context, the decision of modifying our process was taken to optimize the formation of FDCA. In this context, the decision of modifying our process was taken to optimize the FDCA production. Once produced in neat conditions by mixing mucic acid and acid catalyst, ethanol FDCA production. Once produced in neat conditions by mixing mucic acid and acid catalyst, was added to the crude mixture containing the crude FDCA leading to the formation of the target ethanol was added to the crude mixture containing the crude FDCA leading to the formation of the compound (Scheme2). Variations of: (i) the nature and loading of the acid catalyst; (ii) the temperature target compound (Scheme 2). Variations of: (i) the nature and loading of the acid catalyst; (ii) the and (iii) the time of the reaction were studied. The effect of three catalysts (PTSA, methanesulfonic temperature and (iii) the time of the reaction were studied. The effect of three catalysts (PTSA, acid (MSA) and camphorsulfonic acid (CSA)) on the dehydration of mucic acid (1 mmol) was studied ◦ at different temperatures (140–170 C) for 5–120 min keeping the amount of catalyst (1–4 eq) in a Molecules 2019, 24, x FOR PEER REVIEW 4 of 15 methanesulfonic acid (MSA) and camphorsulfonic acid (CSA)) on the dehydration of mucic acid (1 mmol) was studied at different temperatures (140–170 °C) for 5–120 min keeping the amount of catalystMolecules (1–42019 eq), 24 in, 1030 a solvent-free reaction under conventional heating (Table 1). Initial studies4 of 15 were performed for mucic acid (1 mmol) and PTSA (1 eq) as a model reaction at 160 °C for 60 min. Under our conditions, the target FDCA was obtained in 32% yield. Variations of the catalyst loading solvent-free reaction under conventional heating (Table1). Initial studies were performed for mucic showed that a maximal yield of FDCA (41%) was obtained in the presence of two equivalents of the acid (1 mmol) and PTSA (1 eq) as a model reaction at 160 ◦C for 60 min. Under our conditions, the target acid catalyst (Table 1, entry 2). The use of more catalyst did not permit us to increase the FDCA was obtained in 32% yield. Variations of the catalyst loading showed that a maximal yield of productivity.FDCA (41%) At wastemperatures obtained in above the presence 160 °C, ofthe two FDCA equivalents yield decreased of the acid (28% catalyst vs. (Table 41%),1 ,probably entry 2). due to someThe usedegradation of more catalyst and for did temperatures not permit us tobelow increase 160 the °C, productivity. the production At temperatures of FDCA abovewas only 160 ◦12%C, at 140 °Cthe FDCA(Table yield1, entries decreased 16 and (28% 17). vs. 41%),Different probably times due of to reaction some degradation were tested and forwith temperatures the optimized conditionsbelow 160and◦C, 60 the min production seemed ofto FDCAbe the was best only one 12% (Table at 140 1,◦ Centry (Table 2).1, entriesSimilar 16 reaction and 17). profiles Different were obtainedtimes using of reaction MSA were as acid tested catalyst with the (2 optimizedeq) at 160 conditions °C with a and shorter 60 min residence seemed to time be the (30 best min one vs. 60 ◦ min).(Table Interestingly,1, entry 2). CSA Similar was reaction not efficient proﬁles for were producing obtained using FDCA, MSA despite as acid its catalyst low pKa (2 eq) value at 160 of 1.2.C In contrastwith with a shorter the residenceresults claimed time (30 minby vs.Taguchi 60 min). et Interestingly,al. [33], our CSA method was not did efﬁcient not afford for producing the dialkyl 2,3-furandicarboxylateFDCA, despite its low by-product. pKa value of 1.2. In contrast with the results claimed by Taguchi et al. [33], our method did not afford the dialkyl 2,3-furandicarboxylate by-product. Table 1. Dehydration of mucid acid in the presence of acid catalyst for the production of FDCA. Table 1. Dehydration of mucid acid in the presence of acid catalyst for the production of FDCA.

EntryEntry Acid Acid [Acid] [Acid] [eq] [eq] Temperature Temperature [°C] [ ◦C] Time Time [min] [min] Yield Yield of ofFDCA FDCA [%] [%] aa 1 1PTSA PTSA 1 1 160 160 60 60 32 32 2 2PTSA PTSA 2 2 160 160 60 60 41 41 3 3PTSA PTSA 3 3 160 160 60 60 36 36 4 PTSA 4 160 60 34 4 PTSA 4 160 60 34 5 PTSA 5 160 60 37 5 6PTSA MSA 5 1 160 160 60 60 37 34 6 7MSA MSA 1 2 160 160 60 60 34 39 7 8MSA MSA 2 3 160 160 60 60 39 35 8 9MSA MSA 3 4 160 160 60 60 35 35 10 MSA 5 160 60 30 9 MSA 4 160 60 35 11 CSA 1 160 60 4 10 12MSA CSA 5 2 160 160 60 60 30 11 11 13CSA CSA 1 3 160 160 60 60 4 15 12 14CSA CSA 2 4 160 160 60 60 11 12 13 15CSA CSA 3 5 160 160 60 60 15 9 16 PTSA 2 140 60 12 14 CSA 4 160 60 12 17 PTSA 2 170 60 28 15 18CSA PTSA 5 2 160 160 60 5 9 8 16 19PTSA PTSA 2 2 140 160 60 15 12 20 17 20PTSA PTSA 2 2 170 160 60 30 28 30 18 21PTSA PTSA 2 2 160 160 5 90 8 40 22 PTSA 2 160 120 37 19 PTSA 2 160 15 20 23 MSA 2 140 60 15 20 24PTSA MSA 2 2 160 170 30 60 30 25 21 25PTSA MSA 2 2 160 160 90 5 40 8 22 26PTSA MSA 2 2 160 160 120 15 37 30 23 27MSA MSA 2 2 140 160 60 30 15 39 28 MSA 2 160 90 35 24 MSA 2 170 60 25 29 MSA 2 160 120 32 25 MSA 2 160 5 8 a 26The FDCAMSA yield was calculated 2 from liquid 160 chromatography 15analysis with a calibration 30 curve. 27 MSA 2 160 30 39 28 MSA 2 160 90 35 29 MSA 2 160 120 32 a The FDCA yield was calculated from liquid chromatography analysis with a calibration curve.

Molecules 2019, 24, x FOR PEER REVIEW 5 of 15 Molecules 2019,, 24,, 1030x FOR PEER REVIEW 55 of of 15 Using the optimized conditions for the synthesis of FDCA (Table 1, entry 27), the second stage Using the optimized conditions for the synthesis of FDCA (Table 1, entry 27), the second stage of the process was realized by adding dry ethanol (5 mL) to the crude material. Varying the reaction of theUsing process the was optimized realized conditions by adding for dry the ethanol synthesis (5 mL) of FDCA to the (Table crude1 ,material. entry 27), Varying the second the stagereaction of time (4–16 h) at 70 °C and 90 °C the maximal yield of DEFDC was obtained at 90 °C for 8 h (Table 2, thetime process (4–16 h) was at realized70 °C and by 90 adding °C the dry maximal ethanol yield (5 mL) of toDEFDC the crude was material.obtained Varying at 90 °C the for reaction 8 h (Table time 2, entry 5). (4–16entry h)5). at 70 ◦C and 90 ◦C the maximal yield of DEFDC was obtained at 90 ◦C for 8 h (Table2, entry 5).

Table 2. Production of DEFDC starting from mucic acid in a one-pot two steps reaction. Table 2. Production of DEFDC starting from mucic acidacid inin aa one-potone-pot twotwo stepssteps reaction.reaction.

EntryEntry Temperature Temperature [°C] [◦C] Time Time[h] [h] Yield of DEFDC Yield of [%] DEFDC a [%] a Entry Temperature [°C] Time [h] Yield of DEFDC [%] a 1 70 4 15 11 70 70 4 4 15 15 2 70 8 23 22 70 70 8 8 23 23 33 70 70 16 16 29 29 3 70 16 29 44 90 90 4 4 27 27 4 90 4 27 55 90 90 8 8 29 29 5 90 8 29 66 90 90 16 16 30 30 6 90 16 30 a The DEFDC yield was calculated from liquid chromatography analysis with a calibration curve. a Thea DEFDCThe DEFDC yield yield was was calculated calculated from from liquid liquid chromatographychromatography analysis analysis with with a calibration a calibration curve. curve. 2.2. Optimization of the Prepolymers Synthesis and Additional Regioselective Acylation of Glycerol 2.2. Optimization of the Prepolymers Synthesis and Additional RegioselectiveRegioselective AcylationAcylation ofof GlycerolGlycerol After isolated and purified the diethyl ester DEFDC, the synthesis of three types of prepolymers After isolated and puriﬁedpurified the diethyl ester DEFDC,DEFDC, the synthesis of threethree types of prepolymers such as BHEFDC, bis(2,3-dihydropropyl)-2,5-furandicarboxylate (BDHPFDC) and diglycerol such asas BHEFDC, BHEFDC, bis(2,3-dihydropropyl)-2,5-furandicarboxylate bis(2,3-dihydropropyl)-2,5-furandicarboxylate (BDHPFDC) (BDHPFDC) and diglycerol and diglycerol analogue analogue have been investigated. For BHEFDC, a study was realized under conventional heating. haveanalogue been have investigated. been investigated. For BHEFDC, For a BHEFDC, study was a realized study was under realized conventional under conventional heating. When heating. heated When ◦heated at 150 °C for two hours DEFDC conversion was limited to 71% and the yield of atWhen 150 heatedC for twoat 150 hours °C DEFDCfor two conversionhours DEFDC was co limitednversion to 71%was andlimited the to yield 71% of and BHEFDC the yield never of BHEFDC never exceeded 60%. Keeping this temperature unchanged, by solely increasing the exceededBHEFDC 60%.never Keeping exceeded this 60%. temperature Keeping unchanged,this temperature by solely unchanged, increasing by the solely reaction increasing time, a realthe reaction time, a real enhancement of the BHEFDC yield has never been recorded. On the other hand, enhancementreaction time, ofa real the enhancement BHEFDC yield of hasthe neverBHEFDC been yield recorded. has never On thebeen other recorded. hand, On when the theother reaction hand, when the reaction was carried out◦ at 170 and 190 °C, respectively, the DEFDC conversion went up waswhen carried the reaction out at was 170 andcarried 190 outC, at respectively, 170 and 190 the °C, DEFDC respectively, conversion the DEFDC went upconversion progressively went up by progressively by extending both reaction time and temperature. Under the optimized◦ conditions, at extendingprogressively both by reaction extending time both and reaction temperature. time Underand temperature. the optimized Under conditions, the optimized at 190 conditions,C, the almost at 190 °C, the almost complete conversion of DEFDC (95%) needs two hours to yield the prepolymer complete190 °C, the conversion almost complete of DEFDC conversion (95%) needs of DEFD twoC hours (95%) to needs yield thetwo prepolymer hours to yield target the in prepolymer 67% yield. target in 67% yield. The effect of microwave irradiation on the above reaction was also investigated. Thetarget effect in 67% of microwave yield. The irradiationeffect of microwave on the above irradiation reaction on was the also above investigated. reaction was After also a investigated. short survey, After a short survey, batch microwave radiation gave similar results (68% yield) with conventional batchAfter microwavea short survey, radiation batch gavemicrowave similar radiation results (68% gave yield) similar with results conventional (68% yield) heating with for conventional 2 h but at a heating for 2 h but at a lower◦ temperature◦ (150 °C vs. 190 °C) (Scheme 3). lowerheating temperature for 2 h but at (150 a lowerC vs. temperature 190 C) (Scheme (150 3°C). vs. 190 °C) (Scheme 3).

Scheme 3. Synthesis of BHEFDC starting from DEFDC in the presence of Co(Ac)2 under microwave SchemeScheme 3. Synthesis 3. Synthesis of BHEFDC of BHEFDC starting starting from from DEFDC DEFDC in the in presence the presence of Co(Ac) of Co(Ac)under2 under microwave microwave radiation. radiation. 2 radiation. With a similar pKa for the two primary hydroxyl groups and the secondary group, the reactivity With a similar pKa for the two primary hydroxyl groups and the secondary group, the of glycerolWith a didsimilar not permitpKa for regioselectivity the two primary without hydr aoxyl sequence groups of and protection/deprotection the secondary group, steps the reactivity of glycerol did not permit regioselectivity without a sequence of protection/deprotection orreactivity a functionalization of glycerol did of not the permit secondary regioselecti hydroxylvity group. without Usually, a sequence there of are protection/deprotection only a few methods steps or a functionalization of the secondary hydroxyl group. Usually, there are only a few methods tosteps direct or a thefunctionalization regioselective of monoacylation the secondary ofhydroxyl glycerol group. on the Usually, primary there hydroxyl are only group. a few Recently,methods to direct the regioselective monoacylation of glycerol on the primary hydroxyl group. Recently, Slavkoto direct et al.thedeveloped regioselective a new monoacylation catalyst-controlled of gl polycondensationycerol on the primary of glycerol hydroxyl using group. diacyl Recently, chlorides Slavko et al. developed a new catalyst-controlled polycondensation of glycerol using diacyl ofSlavko terephtalic et al. acidsdeveloped or adipic a new acids catalyst-controlle [34]. Herein, thed authors polycondensation employed an of additional glycerol diarylboronicusing diacyl chlorides of terephtalic acids or adipic acids [34]. Herein, the authors employed an additional acidchlorides catalyst of terephtalic to form preferentially acids or adipic glycerol-derived acids [34]. Herein, linear polyester.the authors Besides, employed it isan well additional known diarylboronic acid catalyst to form preferentially glycerol-derived linear polyester. Besides, it is well thatdiarylboronic enzymatic acid controlled catalyst to polymerization form preferentially of glycerol glycerol-derived is more or linear less ablepolyester. to generate Besides, linear it is well and known that enzymatic controlled polymerization of glycerol is more or less able to generate linear branchedknown that polyesters enzymatic [35 –controlled37]. In order polymerization to produce the of corresponding glycerol is more the or tetrahydroxylated less able to generate prepolymer linear and branched polyesters [35–37]. In order to produce the corresponding the tetrahydroxylated and branched polyesters [35–37]. In order to produce the corresponding the tetrahydroxylated

Molecules 2019, 24, 1030 6 of 15 Molecules 2019, 24, x FOR PEER REVIEW 6 of 15

◦ prepolymerBDHPFDC, BDHPFDC, our preceding our procedure preceding was procedure applied was at 160 appliedC for at 13 160 h. °C Similarly, for 13 h. the Similarly, batch microwave the batch ◦ ◦ microwaveradiation permitted radiation us permitted to reduce us the to reaction reduce timethe reac (2 htion vs. 13time h) and(2 h thevs. 13 temperature h) and the (150 temperatureC vs. 160 (150C) °Cwith vs. the 160 synthesis °C) with of the BDHPFDC synthesis in of 80% BDHPFDC yield (Scheme in 80%4). Ityield was notable(Scheme that 4). anIt was unexpected notable efficientthat an unexpectedregioselective efficient monoacylation regioselective of glycerol monoacylation on its primary of glycerol hydroxyl on its group primary was hydroxyl observed group permitting was observedthe formation permitting of linear the polymer. formation To of clearly linear determinepolymer. To the clearly regioselectivity determine ofthe our regioselectivity trans-esterification, of our trans-esterification,2D-NMR experiments 2D-NMR were employed experiments to estimate were employ the selectivityed to estimate of the the reaction selectivity between of the the reaction primary betweenhydroxyl the group primary and the hydroxyl secondary group hydroxyl and group the secondary furnishing hydroxyl the linear prepolymergroup furnishing and the the branched linear prepolymerprepolymers, and respectively the branched (Figure prepolymers, S1). After investigation,respectively (Figure the amount S1). After of the investigation, branched dicarboxylates the amount ofpresent the branched in the solid dicarboxylates was estimated present at a maximumin the solid of was 3%. estimated In our opinion at a maximum this quite of regioselective 3%. In our opinionBDHPFDC this synthesis quite regioselective is probably promoted BDHPFDC by thesynt directhesis complexationis probably ofpromoted Co (II) onby glycerol the direct and complexationthe metal remained of Co (II) attached on glycerol to all and reaction the meta intermediatesl remained untilattached the to transesterification all reaction intermediates processes untilwere the completed. transesterification processes were completed.

SchemeScheme 4. Synthesis 4. Synthesis of BDHPFDC of BDHPFDC starting fromstarting DEFDC from in theDEFDC presence in ofthe Co(Ac) presence2 under of microwaveCo(Ac)2 under radiation. microwave radiation. Applying the process to diglycerol as polyol was not successful and it was impossible for us to ◦ isolateApplying the desired the process diol derivatives to diglycerol whatever as polyol the temperatures was not successful used (160 and and it was 180 impossibleC). for us to isolate the desired diol derivatives whatever the temperatures used (160 and 180 °C). 2.3. Optimization of Solvent-Free Poly Trans-Esteriﬁcation and Solids Characterizations 2.3. OptimizationCurrently, our of Solvent-Free strategy involved Poly Trans- to mixEsterification DEFDC (1 eq)and withSolid BHEFDCs Characterizations (1 eq), BDHPFDC (1 eq) and diglycerolCurrently, (1 eq), our separately strategy ininvolved the presence to mix of DEFDC catalytic (1 amount eq) with of BHEFDC Co(Ac)2 in(1 solventeq), BDHPFDC free conditions (1 eq) at 160 ◦C for 3 h. In several cases, dark brown solids or powders were isolated prior to further and diglycerol (1 eq), separately in the presence of catalytic amount of Co(Ac)2 in solvent free conditionsanalysis. All at materials160 °C for were 3 h. insolubleIn several in cases, the common dark brown organic solids solvents or powders currently were employed isolated inprior steric to furtherexclusion analysis. chromatography All materials (SEC) were analysis. insoluble Starting in the common from DEFDC organic and solvents BHEFDC, currently the target employed polymer in 1 stericPEF was exclusion obtained chromatography (Scheme5). The (SEC)H-NMR analysis spectrum. Starting of PEF from corroborated DEFDC and the resultBHEFDC, reported the target in the polymerliterature PEF [21,26 was] and obtained showed in(Scheme different 5). samples The 1H-NMR studied spectrum at successive of residencePEF corroborated time the progressivethe result reporteddisappearance in the ofliterature signal of [21,26] methyl and group showed at 1.36 in different ppm which samples is representative studied at successive of the DEFDC residence ester timemoieties the progressive (Figure S2). disappearance The small peak of signal located of meth at 3.34yl group ppm was at 1.36 attributed ppm which to the is representative primary alcohol of 13 theofBHEFDC. DEFDC ester The moietiesC-NMR (Figure spectrum S2). of The PEF small was identicalpeak located with at that 3.34 published ppm was [ 21attributed,26] (Figure to 1thea). primaryApparently, alcohol one ofof the BHEFDC. major defaults The 13 ofC-NMR this synthetic spectrum method of PEF is the was absence identical of control with regardingthat published chain [21,26]termination (Figure with 1a). an Apparently, apparent suppression one of the ofmajor the ethyldefaults ester of functions. this synthetic method is the absence of control regarding chain termination with an apparent suppression of the ethyl ester functions.

Molecules 2019, 24, 1030 7 of 15 MoleculesMolecules 2019 2019, 24, 24, x, xFOR FOR PEER PEER REVIEW REVIEW 7 7of of 15 15

SchemeScheme 5. 5. Synthesis Synthesis of of PEF PEF in in the the presence presence of of Co(Ac) Co(Ac)2. 22.

1313 1313 1 1 FigureFigure 1. 1.1. ( a()a ) C-NMR13C-NMRC-NMR spectrum spectrum of of PEF PEF in in DMSO- DMSO-DMSO-d6d; 6(;;( b(,bd,)d ) C-13C-C- and and H-NMR1H-NMRH-NMR spectra spectra spectra of of PHPF PHPF in in 13 d c1313 d DMSO-DMSO-d6d and6 andand (c ( ()c )) C-NMRC-NMRC-NMR of of ofPDGF PDGF PDGF measured measured measured in in inDMSO- DMSO- DMSO-d6d. 66. .

StartingStarting from from DEFDC DEFDC and and BDHPFDC, BDHPFDC, the the target target polymer polymer PHPF PHPF having having a aglycerol glycerol moiety moiety was was obtainedobtained (Scheme (Scheme 6). 66).). The TheThe principal principalprincipal risk riskrisk of ofof this thisthis reaction reactionreaction was waswas the thethe possibility possibilitypossibility of ofof forming formingforming branched branchedbranched polyesterspolyesters due due to to the the presence presence of of two two secondary secondary hydroxyl hydroxyl hydroxyl groups groups groups on on on the the the glycerol-based glycerol-based glycerol-based prepolymer. prepolymer. prepolymer. However,However, compared compared to to an an already already described described non-linear non-linear polymer polymer [28], [28], [28 ],our our result result is is coherent coherent with with a a linearlinear structure. structure. The The signal signal of of the the primary primary alcohol alcohol of of the the prepolymer prepolymer does does not not remained remained observable observable 1 1 on the1 H-NMR spectrum of the sample. Moreover, the1 H-NMRs of the glycerol-based copolymer onon the the H-NMR1H-NMR spectrum spectrum of of the the sample. sample. Moreover, Moreover, the the H-NMRs1H-NMRs of of the the glycerol-based glycerol-based copolymer copolymer clearlyclearly showed showed bands bands between between 3.17 3.17 and and 3.38 3.38 ppm ppm th thatthatat match match the the -CH- -CH- of of the the secondary secondary hydroxyl hydroxyl groupgroup of of glycerol glycerol (Figure (Figure 1d).1 1d).d). Anot AnotherAnotherher broad broadbroad signal signalsignal was waswas also alsoalso observable observableobservable from fromfrom 4.01 4.014.01 and andand 4.33 4.334.33 ppm ppmppm that thatthat 13 corresponds to the methylene groups of the polyol included in the polyester chains. The13 C-NMR correspondscorresponds to to the the methylene methylene groups groups of of the the polyol polyol included included in in the the polyester polyester chains. chains. The The 13C-NMRC-NMR spectrumspectrum of ofof PHPF PHPFPHPF was was was also also moremore more simplifiedsimplified simplified compared comp comparedared to to itsto its branchedits branched branched counterparts counterparts counterparts [28 ][28] showing[28] showing showing only onlyonlyfive five peaks:five peaks: peaks: 48.5, 48.5, 48.5, 65.9, 65.9, 65.9, 119.3, 119.3, 119.3, 146.0 146.0 146.0 and and 157.1and 157.1 157.1 ppm ppm ppm (Figure (Figure (Figure1b). 1b). 1b). Starting from DEFDC and diglycerol, a more usual poly transesterification was carried out under conventional heating at 160 ◦C for 3 h. Compared to the 13C-NMR spectrum of PHPF, the number of peaks was higher considering those initially expected, evidence of possible branching of the polymer chains (Figure1c). The 1H-NMRs of this product material are also given (Figure S3). According to the results displayed in the COSY spectrum of BDHPFDC, some similarities can be found with spectra obtained from a sample of PDGF in DMSO-d6. Located in the center part of the corresponding spectrum grid four signals around 4.5 ppm in both directions form a square and are representative of the furan

Molecules 2019, 24, 1030 8 of 15

rings bound to diglycerol through a primary alcohol ester made of CH2 groups (Figure S4). Besides, at 3.6 and 5.1 ppm, there are two signals rather characteristic of furan moieties bonded with a secondary alcohol group that corresponds to the –CH- group of the diglycerol. Those results are evidence of the non-linearMolecules 2019 nature, 24, x FOR of thePEER formed REVIEW PDGF polymer. 8 of 15

Scheme 6. Synthesis of PHPF in the presence of Co(Ac)22.

InStarting order tofrom complete DEFDC the and spectrochemical diglycerol, a analysis, more usual FT-IR poly spectra transesterification of the three polymers was carried PEF, PHPF out andunder PDGF conventional provided usheating important at 160 information °C for 3 h. about Compared our materials to the (Figure13C-NMR S5). spectrum Thus, all of characteristic PHPF, the vibrationnumber of bands peaks of was PEF higher were considering detected in thethose spectrum initially andexpected, reported evidence as follows: of possible 2881 ( λbranchingCH2), 1717 of −1 (C=0),the polymer 1582 (λ chainsC=C), 1271(Figure (C-O), 1c).but The also 1H-NMRs 963, 832 of and this 764 product cm which material are theare bending also given motions (Figure always S3). associatedAccording withto the the results 2,5-disubstituted displayed in furan the ring.COSY For sp theectrum poly(2,5-furan of BDHPFDC, dicarboxylic some similarities acid-co-glycerol) can be PHPFfound andwith PDGF,spectra the obtained material from was a analyzedsample ofand PDGF compared in DMSO- tod FT-IR6. Located spectrum in the obtained center part from of the branchedcorresponding polymer spectrum recently grid synthesized four signals by around Amarasekara 4.5 ppm etin al. both [28 ].directions In the PHPF form spectrum,a square and it was are possiblerepresentative to observe of the the furan characteristic rings bound bands to diglyc of furan-basederol through polyesters a primary located alcohol respectively ester made atof 1733CH2 −1 (C=O),groups 1157(Figure and S4). 1276 Besides, cm (C-O-C).at 3.6 and Unfortunately, 5.1 ppm, there it are was two impossible signals rather for us characteristic to detect the presenceof furan ofmoieties the typical bonded -OH with vibration a secondary bands. Onalcohol the other group side, that all corresponds representative to bandsthe –CH- of the group furan-based of the polyestersdiglycerol. were Those effectively results are present. evidence For of PDGF, the no then-linear bands nature of –OH of vibrations the formed were PDGF clearly polymer. visible around −1 −1 3297In cm orderand to allcomplete other characteristic the spectrochemical bands located analysis, at 2955,FT-IR 1720,spectra 1584 of cmthe three, but polymers also 1128 PEF, and −1 1278PHPF cm and attributedPDGF provided to the diglycerol us important moiety. information about our materials (Figure S5). Thus, all characteristicThe DSC vibration thermograms bands of ourof PEF synthesized were detected PEF, PHPF, in the and spectrum PDGF wereand reported measured as (Figure follows:2). 2881 Due to(λ aCH possible2), 1717 high (C=0), crystallinity 1582 (λ C=C), level, the1271 melting (C-O),point but alsoTm recorded963, 832 forand PEF 764 gave cm−1 a which value aare little the bit bending inferior ◦ thanmotions the normalalways valueassociated of 211 withC generallythe 2,5-disubstitute encounteredd furan in the ring. literature For the [10 poly(2,5-furan,15,19], but still dicarboxylic superior to ◦ 183acid-co-glycerol)C. This result PHPF could and be connected PDGF, the to thematerial length was of the analyzed polyester and chain compared formed to during FT-IR the spectrum process. Aobtained normal from crystallization the branched exotherm polymer was recently present synthesized in the thermogram by Amarasekara and the material et al. [28]. expressed In the aPHPF cold ◦ crystallizationspectrum, it was temperature possible Tcto atobserve 142 C. the In comparison, characteristic PHPF bands did of not furan-based show an endothermic polyesters peak located but ◦ ratherrespectively two strong at 1733 peaks (C=O), located 1157 at and 345 1276 and 379cm−1 C,(C-O-C). respectively, Unfortunately, in the thermogram. it was impossible This result for couldus to bedetect attributed the presence as the ﬁrstof the evidence typical of-OH a possible vibration modiﬁcation bands. On ofthe the other amorphous side, all structurerepresentative of the bands material of givingthe furan-based later a glassy polyesters appearance were after effectively a treatment presen att. higher For PDGF, temperatures. the bands For of PDGF, –OH thevibrations thermogram were ◦ displayedclearly visible at temperatures around 3297 superior cm−1 and to all 250 otherC,two characteristic successive bands crystallization located at values 2955,of 1720, Tc observed 1584 cm at−1, ◦ ◦ 267but also and 3221128 C.and Curiously, 1278 cm−1 after attributed further to warming the diglycerol cycles, moiety. a new peak started to appear at 350 C. It is possibleThe toDSC attribute thermograms this phenomenon of our synthesized to degradation PEF, orPHPF, rearrangements and PDGF ofwere the polymermeasured backbone. (Figure 2). Due to a possible high crystallinity level, the melting point Tm recorded for PEF gave a value a little bit inferior than the normal value of 211 °C generally encountered in the literature [10,15,19], but still superior to 183 °C. This result could be connected to the length of the polyester chain formed during the process. A normal crystallization exotherm was present in the thermogram and the material expressed a cold crystallization temperature Tc at 142 °C. In comparison, PHPF did not show an endothermic peak but rather two strong peaks located at 345 and 379 °C, respectively, in the thermogram. This result could be attributed as the first evidence of a possible modification of the amorphous structure of the material giving later a glassy appearance after a treatment at higher temperatures. For PDGF, the thermogram displayed at temperatures superior to 250 °C, two successive crystallization values of Tc observed at 267 and 322 °C. Curiously, after further warming cycles, a new peak started to appear at 350 °C. It is possible to attribute this phenomenon to degradation or rearrangements of the polymer backbone.

Molecules 2019, 24, 1030 9 of 15 Molecules 2019, 24, x FOR PEER REVIEW 9 of 15 Molecules 2019, 24, x FOR PEER REVIEW 9 of 15

Figure 2. DSC thermograms of ( a) PEF and ( b) PHPF ( c) PDGF after quenching their melted solution Figure 2. DSC thermograms of (a) PEF and (b) PHPF◦ (c) PDGF after quenching their melted solution with liquid N2.. Heating Heating and and cooling cooling rate rate was was 10 10 °C/min.C/min. with liquid N2. Heating and cooling rate was 10 °C/min.

TGA measurements were recorded for two of our polymeric samples for evaluating the stability stability TGA measurements were recorded for two of our polymeric samples for evaluating the stability of our polymers at the higher temperature temperature in in air air or or under under a a nitrogen nitrogen atmosphere atmosphere (Figure (Figure 33).). For PEF, of our polymers at the higher temperature in air or under◦ a nitrogen atmosphere◦ (Figure 3). For PEF, the material is quite stable for temperatures aboveabove 220 °C,C, but around 380 °CC the material lost about the material is quite stable for temperatures above 220 °C, but around 380 °C the material lost about 60% of its total mass. This This result result is is in in accordance accordance with with literature literature [10,15,19]. [10,15,19]. For For PHPF, PHPF, the mechanism 60% of its total mass. This result is in accordance with literature [10,15,19]. For PHPF, the mechanism appeared to to be be more more complicated. complicated. In In fact, fact, the the glassy glassy black black solid solid already already lost lost around around 4% 4% of ofits itsmass mass at appeared◦ to be more complicated. In fact, the glassy black solid already lost around 4%◦ of its mass at 200at 200 °C, C,but but the the DTGA DTGA curve curve clearly clearly showed showed two two peaks peaks located located at at 290 290 and and 380 380 °C,C, respectively 200 °C, but the DTGA curve clearly showed two peaks located at 290 and 380 °C, respectively (Figure S6). The The first ﬁrst one one could could be be representative representative of of a a partial de dehydrationhydration of the polyester chain (Figure S6). The first one could be representative of a partial dehydration of the polyester chain localized on the glycerol moiety followed by structural transformations that that could could occur at higher localized on the glycerol moiety followed by structural transformations that could occur◦ at higher temperatures. Finally,Finally, both both polymers polymers undergo undergo mass mass variations variations at temperatures at temperatures below below 400 C,400 this °C, result this temperatures. Finally, both polymers undergo mass variations at temperatures below 400 °C, this resultis also is in also agreement in agreement with the with above the above DSC measurements. DSC measurements. result is also in agreement with the above DSC measurements. 100 100 80 80 60 60 40 PEF 40 PEF Weight (%)

Weight (%) PHPF PHPF 20 20 0 0 199 249 299 349 399 199 249 299 349 399 Temperature (°C) Temperature (°C)

Figure 3. TGA traces curves of PEF and PHPF. Figure 3. TGA traces curves of PEF and PHPF. Figure 3. TGA traces curves of PEF and PHPF.

Molecules 2019, 24, 1030 10 of 15

MoleculesThe crystal 2019, 24, structuresx FOR PEER REVIEW of PEF and PHPF were estimated by XRD (Figure4).10 For of 15 PEF, ◦ the diffractogramThe crystal displayed structures three of PEF representative and PHPF sharpwere signalsestimated observed by XRD at (Figure 18, 22 and4). 28For ,PEF, characteristic the of a semi-crystallinediffractogram displayed material. three On representative the contrary, sharp the glycerol-basedsignals observed PHPF at 18, was22 and completely 28°, characteristic amorphous and didof a notsemi-crystalline show a real material. crystallinity On the pattern. contrary, Unsurprisingly, the glycerol-based PDGF PHPF was was also completely an amorphous amorphous material and didand did not not display show a peaks real crystallinity or signals pattern. in the Unsurprisingly, XRD analysis. PDGF FE-SEM was also observations an amorphous of PEFmaterial powder morphologyand did displayednot display somepeaks kind or signals of ﬁbrous in the and XRD apparently analysis. porousFE-SEM network.observations In associationof PEF powder with this resultmorphology the EDX spectrum displayed showedsome kind that of fibrous the puriﬁed and appa materialrently porous was rich network. in carbon In association and oxygen, with butthis some tracesresult of cobalt the EDX salts spectrum remained showed entrapped that the insidepurified the ma material.terial was rich Conversely, in carbon inand the oxygen, PHPF but photograph, some traces of cobalt salts remained entrapped inside the material. Conversely, in the PHPF photograph, it it is possible to observe larger and entangled structures, unfortunately loaded with more cobalt traces, is possible to observe larger and entangled structures, unfortunately loaded with more cobalt traces, provenproven by the by corresponding the corresponding EDX EDX spectrum spectrum (Figure (Figur S7).e S7). This This result result could could be suggested be suggested by theby presencethe of a greatpresence number of a ofgreat hydroxyl number groups of hydroxyl present groups on the present surface on of the the surface material of ablethe material to complex able a to certain amountcomplex of the a certain catalyst. amount of the catalyst.

FigureFigure 4. XRD 4. XRD diffractograms diffractograms andand SEMSEM images of of synthesized synthesized (a) (PEFa) PEF and and (b) PHPF. (b) PHPF.

In orderIn order to determine to determine the the sustainability sustainability ofof our pr processes,ocesses, EcoScale EcoScale has has been been calculated calculated as a rapid as a rapid metricmetric [38] for[38] the for optimized the optimized syntheses syntheses of FDCA, of FDCA, DEFDC, DEFDC, BHEFDC BHEFDC and BDHPFDC. and BDHPFDC. For the For production the of theproduction polymers of PEF, the polymers PHPF and PEF, PDGF PHPF with and undetermined PDGF with undetermined yields and yields molecular and molecular weights weights the EcoScale wasthe not EcoScale calculated. was not The calculated. values obtained The values using obtained theEcoscale using the toolEcoscale allow tool us allow to rank us to our rank optimized our experimentsoptimized as experiments follow: acceptable as follow: reactions acceptable conditions reactions forconditions the synthesis for the ofsynthesis FDCA of with FDCA a total with score a of total score of 68; inadequate reaction conditions for the synthesis of DEFDC with a total score of 32; 68; inadequate reaction conditions for the synthesis of DEFDC with a total score of 32; excellent reaction excellent reaction condition for the synthesis of BHEFDC and BDHPFDC, with total scores of 75 and condition for the synthesis of BHEFDC and BDHPFDC, with total scores of 75 and 81, respectively. 81, respectively. 3. Experimental Section 3. Experimental Section 3.1. General Information 3.1. General Information EthanolEthanol absolute absolute (99.5%, (99.5%, extra extra dry), dry), mucic mucic acid acid (98%), (98%), diglycerol, diglycerol, ethylene ethylene glycol glycol (99%, (99%, extra extra pure), cobaltpure), (II) acetatecobalt (II) tetrahydrate acetate tetrahydrate (Co(Ac)2, (Co(Ac) 4H2O; 98%)2, 4H2O; and 98%) methanesulfonic and methanesulfonic acid (MSA, acid (MSA, 99% extra 99% pure) wereextra purchased pure) were from purchased Acros Organics from Acros (Pittsburgh, Organics PA, (Pittsburgh, USA). Other PA, reagentsUSA). Ot suchher reagents as p-toluenesulfonic such as acid monohydratep-toluenesulfonic (PTSA acid·H monohydrate2O; 98%), furan-2,5-dicarboxylic (PTSA·H2O; 98%), acidfuran-2,5-dicarboxylic (98%) and glycerol acid (reagent (98%) plus and > 99% GC) wereglycerol obtained (reagent from plus Alfa> 99% Aesar GC) were (Ward obtained Hill, MA, from USA) Alfa andAesar Sigma (Ward Aldrich Hill, MA, (Saint USA) Louis, and Sigma MO,USA). All chemicalsAldrich (Saint were Louis, used asMO, received USA). All without chemicals further were purification. used as received without further purification. Transesterifications were realized with a microwave apparatus (Monowave 300, Anton Paar, Transesterifications were realized with a microwave apparatus (Monowave 300, Anton Paar, Graz, Graz, Austria) at 600 rpm for the desired time. The reaction vessel was purged three times with Austria) at 600 rpm for the desired time. The reaction vessel was purged three times with nitrogen. nitrogen. The temperature in the reaction vessel was monitored by means of an IR sensor and the The temperaturevial was pressurized in the reactionin regard vessel to the wasnormal monitored vapor pressure by means of the of mixture an IR sensor at defined and reaction the vial was pressurizedtemperature. in regard to the normal vapor pressure of the mixture at defined reaction temperature. 1 13 NuclearNuclear magnetic magnetic resonance resonance ( (H-1H- andand 13C-NMR)C-NMR) spectra spectra were were recorded recorded on an on Avance an Avance III 400 III 400 spectrometerspectrometer (Bruker, (Bruker, Billerica, Billerica, MA, MA, USA) USA) equipped equipped with awith BBFO a probeBBFO operatingprobe operating at room at temperature. room Othertemperature. sequences suchOther as sequences COSY (1H- such1H), as direct COSY HSQC (1H-1H), (1 H-direct13C) HSQC and HMBC (1H-13C) long and range HMBC coupling long range (1H- 13C) were applied on monomers BHEFDC and PDGF polymers. Chemical shifts (δ) are quoted in parts Molecules 2019, 24, 1030 11 of 15 per million (ppm). Coupling constants are quoted in Hertz. Sometimes, comparison with already described compounds has been used to confirm the NMR peak assignments. For high performance liquid chromatography (HPLC), each sample was analyzed separately by means of a Prominence HPLC system (Shimadzu, Kyoto, Japan). Unreacted mucic acid was detected with a low temperature evaporative light scattering detector (ELSD-LT II) and the products concentration was estimated with a UV-Vis detector (SPD-M20A) at a wavelength of 265 nm. The column used was a Grace (Columbia, MD, USA) Prevail C18 column (250 × 4.6 mm 5 µm). The mobile phase was MeOH-water (9:1) solution flowing at rate of 0.5 mL/min. The column oven temperature was set at 40 ◦C. Differential Scanning Calorimetry (DSC) was conducted on a DSC 8MC apparatus (Mettler-Toledo, Columbus, OH, USA) using aluminium pans. Scans were conducted under nitrogen with a heating rate of 10 ◦C/min in the temperature range of 40–250 ◦C. Thermogravimetric analysis (TGA) was carried out on an Setsys Evolution analyzer (ATG Setaram, Caluire, France) equipped with an aluminium cell, using aluminium pans to encapsulate the samples. Typically, samples were heated at a constant rate of 10 ◦C/min from room temperature up to 550 ◦C, under a helium flow of 50 mL/min. The thermal decomposition temperature was taken at the onset of significant (≥5%) weight loss from the heated sample. FT-IR (ATR) spectra were recorded on FT-IR 4000 (Jasco, Tsukuba, Japan) in a range of 650 to 4000 cm−1. FE- Scanning Electron Microscopy (SEM)- Energy Dispersive X-ray Diffraction (EDX) analysis of polymer powders was performed on a Quanta FEG 250 instrument (FEI, Hillsboro, OR, USA) equipped with a microanalysis detector for EDX from Bruker. SEM micrographs acquired in secondary electron mode were obtained at low vacuum, 15 Kv accelerating voltage and 10 mm working distance. XRD experiments were recorded on a X’pert MRD diffractometer (Pan Analytic/Philips, Eindhoven, the Netherlands 40 Kv, 30 mA) using Cu Kα (λ = 0.151418 nm) radiation. Scans were performed over a 2θ range from 10 to 80, at step size of 0.018◦ with a counting time per steps of 5 s.

3.2. Synthesis and Characterization

3.2.1. Synthesis of Diethyl Furan-2,5-Dicarboxylate (DEFDC) A suspension of mucic acid (210.0 mg, 1.0 mmol) in the presence of MSA (192.0 mg, 2.0 mmol) was stirred at 160 ◦C for 30 min using an oil bath until the reaction mixture turned brown. Then, after cooling the mixture to 70 ◦C, dry ethanol (5 mL) was added and the mixture was heated progressively from 70 to 90 ◦C for additional 8 h. The reaction mixture was allowed to return to the room temperature, poured in water and extracted with ethyl acetate. The organic layer was separated, washed with aqueous NaHCO3 saturated solution. The organic liquid was isolated, dried on MgSO4 and evaporated in vacuum to afford a brown solid which was puriﬁed on silica gel column chromatography using a mixture of EtOAc-cyclohexane (1:1) as eluent to afford the target DEFDC as a ◦ 1 white crystal (m = 61.5 mg; yield = 29% for two steps); Mp = 86 C; H-NMR (CDCl3): δ 1.32 (t, 6H, 13 J = 7.2 Hz, CH3), 4.33 (m, 4H, CH2), 7.13 (s, 2H, CH Furan ring) ppm; C-NMR (CDCl3): δ 14.3, 61.6, 118.2, 149.0, 158.0 ppm.

3.2.2. Synthesis of Bis(Hydroxyethyl)-2,5-Furandicarboxylate (BHEFDC) DEFDC (212.1 mg, 1.0 mmol) was mixed with EG (4.0 mL) in presence of 20.0 mg (0.08 mmol) of Co(Ac)2, 4H2O. The mixture was introduced in a 25 mL round bottom ﬂask equipped with water separator and nitrogen inlet. The reaction was carried out at a selected temperature from 150 for 2 h under microwave radiation. Finally, the puriﬁcation was realized as reported previously affording the compound as colored crystals [21] (m = 166.0 mg; yield = 68%); The material was hygroscopic; 1 H-NMR (CDCl3): δ 3.87 (m, 4H, CH2), 4.37 (m, 4H, CH2), 4.59 (s, 2H, OH), 7.17 (s, 2H, CH Furan 13 ring); C-NMR (CDCl3): δ 60.6, 67.2, 118.9, 146.4, 158.1. Molecules 2019, 24, 1030 12 of 15

3.2.3. Synthesis of Bis(2,3-Dihydropropyl)-2,5-Furandicarboxylate (BDHPFDC)

DEFDC (212.1 mg, 1.0 mmol) was mixed with glycerol (3.0 mL) in presence of Co(Ac)2·4H2O (20.0 mg, 0.08 mmol). The mixture was introduced in a 25 mL round bottom ﬂask equipped with water separator and nitrogen inlet. The reaction was carried out at a selected temperature from 150 for 2 h under microwave radiation. After performed the reaction, the sample tube was left at room temperature for 24 h, then a product started to recrystallize slowly from the viscous solution. The product was recovered by centrifugation after addition of 1 mL of cold water to the mixture. Then the collected crystal was dried in vacuum to afford the prepolymer as a white solid. (m = 243.3 mg; yield = 80%). ◦ −1 1 Mp = 83 C; FT-IR: 2850-2900; 1728 (C=O); 1279; 1230; 1154; 760 cm ; H-NMR (DMSO-d6): δ 3.59 (m, 13 4H, CH2), 3.98 (m, 2H, CH), 4.24–4.40 (m, 4H, CH2), 7.32 (s, 2H, CH Furan ring); C-NMR (DMSO-d6): δ 62.0, 66.4, 69.3, 119.6, 146.2, 159.3; +ESI-TOF-MS m/z = 304 + 1 (M+H+).

3.2.4. General Melt Polytransesteriﬁcation DEFDC (144.2 mg, 0.68 mmol) and 1 equivalent of BHEFDC (166.0 mg, 0.68 mmol), BDHPFDC (206.8 mg, 0.68 mmol) or diglycerol (112.9 mg, 0.68 mmol) were mixed with Co(Ac)2·4H2O (20.0 mg (0.08 mmol). The solvent free mixture was stirred at 160 ◦C under nitrogen atmosphere until all material melted for a minimum of three hours to complete the polymerization. Later the resulted dark brown mixture is allowed to return to the room temperature, each solid was triturated in MeOH, ﬁltrated and dried in vacuum prior to physicochemical characterization. 1 13 For PEF: H-NMR (DMSO-d6): δ 7.4 (s, CH furan rings), 4.65 (s, CH2); C-NMR (DMSO-d6): δ 63.0 (CH2), 119.4 (CH), 145 (Cq Furan), 157.1 (Cq, C=O). 1 13 For PHPF: H-NMR (DMSO-d6): δ 7.42 (s, CH furan rings), 4.32 (s, CH2), 3.38 (CH); C-NMR (DMSO-d6): δ 48.5 (CH), 66.0 (CH2), 119.3 (CH), 146.0 (Cq Furan), 157.1 (Cq, C=O). 1 For PDGF: H-NMR (DMSO-d6): δ 7.42 (s, CH furan rings), 5.50–3.20 (m, CH2 and CH), 1.32 (m, CH3).

4. Conclusions A new process for the synthesis of the diethyl ester of FDCA starting from mucic acid was developed in a one-pot two step procedure furnishing the target diester in 29% yield. Using this platform molecule, two prepolymers were produced by transesteriﬁcation with ethylene glycol and glycerol and Co(Ac)2·4 H2O as catalyst in 68% and 80% yields, respectively. Then, different kinds of furan-based polyesters were produced using a solvent-free Co(Ac)2·4H2O catalyzed polytransesteriﬁcation between FDCA diethyl ester and two polyol- derived prepolymers (PEF and PHPF). The glycerol-based linear polyester seems to be subject to some kind of further rearrangement causing reticulation of the material, when heated at temperatures above 370 ◦C. However, due to the increasing number of hydroxyl groups on the periphery of the material, the viscous resin of PDGF was clearly a water soluble material. This methodology should be extended to other biosourced diols or PTA-based prepolymers to access new copolymers of interest. The resulting linear PHPF and branched PDGF polymers could be also functionalized on their free hydroxyl group for future biological or medicinal applications.

Supplementary Materials: The following are available online. Figure S1: 2D-NMR sequences of BDHPFDC: 1 1 1 13 1 COSY ( H- H) and HMBC ( H- C), Figure S2: H NMR of PEF in DMSO-d6 after complete polymerization, Figure S3: 1H NMR of PDGF after polymerization, Figure S4: Cosy (1H-1H) spectrum of PDGF, Figure S5: FT-IR spectra of (a) PEF; (b) PHPF and (c) PDGF, Figure S6: TG-DTG curves of (a) PEF and (b) PHPF, Figure S7: EDX spectra of (a) PEF and (b) PHPF. Author Contributions: F.D. and C.L. conceived and designed the experiments; D.Z. performed the experiments; D.Z., F.D. and C.L. analyzed the data; C.L. contributed reagents/materials/analysis tools; F.D. and C.L. wrote the paper. Funding: This research received no external funding. Acknowledgments: D.Z. would like to thank the China Scholarship Council (CSC) for financial support. Conflicts of Interest: The authors declare no competing financial interest. Molecules 2019, 24, 1030 13 of 15

References

1. Pal, P.; Saravanamurugan, S. Recent advances on development of 5-hydroxymethylfurfural oxidation with base (non-precious) metal-containing catalysts. ChemSusChem 2019, 12, 145–163. [CrossRef][PubMed] 2. Kucherov, F.A.; Romashov, L.V.; Galkin, K.I.; Ananikov, V.P. Chemical transformations of biomass-derived C6-furanic platform chemicals for sustainable energy research, material science, and synthetic building blocks. ACS Sustain. Chem. Eng. 2018, 6, 8064–8092. [CrossRef] 3. Zhang, Z.; Huber, G.W. Catalytic oxidation of carbohydrates into organic acids and furan chemicals. Chem. Soc. Rev. 2018, 47, 1351–1390. [CrossRef][PubMed] 4. Sajid, M.; Zhao, X.; Liu, D. Production of 2,5-furandicarboxylic acid (FDCA) from 5-hydroxymethylfurfural (HMF): Recent progress focusing on the chemical-catalytic routes. Green Chem. 2018, 20, 5427–5453. [CrossRef] 5. Zhang, Z.; Deng, K. Recent advances in the catalytic synthesis of 2,5-furandicarboxylic acid and its derivatives. ACS Catal. 2015, 5, 6529–6544. [CrossRef] 6. Partenheimer, W.; Grushin, V.V. Synthesis of 2,5-diformylfuran and furan-2,5-dicarboxylic acid by air-oxidation of 5-hydroxymethylfurfural. Unexpectedly selective aerobic oxidation of benzyl alcohol to benzaldehyde with metal=bromide catalysts. Adv. Synth. Catal. 2001, 343, 102–111. [CrossRef] 7. Saha, B.; Dutta, S.; Abu-Omar, M.M. Aerobic oxidation of 5-hydroxymethylfurfural with homogeneous and nanoparticulate catalysts. Catal. Sci. Technol. 2012, 2, 79–81. [CrossRef] 8. Lolli, A.; Albonetti, S.; Utili, L.; Amadori, R.; Ospitali, F.; Lucarelli, C.; Carani, F.Insights into the reaction mechanism for 5-hydroxymethylfurfural oxidation to FDCA on bimetallic Pd-Au nanoparticles. Appl. Catal. A Gen. 2015, 504, 408–419. [CrossRef] 9. Abonetti, S.; Pasini, T.; Lolli, A.; Blosi, M.; Piccinini, M.; Dimitratos, N.; Lopez-Sanchez, J.A.; Morgan, D.J.;

Carley, A.F.; Hutchings, G.J. Selective oxidation of 5-hydroxymethyl-2-furfural over TiO2-supported gold-copper catalysts prepared from preformed nanoparticles: Effect of Au/Cu ratio. Catal. Today 2012, 195, 120–126. [CrossRef] 10. Rass, M.A.; Essayem, N.; Besson, M. Selective aerobic oxidation of 5-HMF into 2,5-furandicarboxylic acid

with Pt catalysts supported on TiO2- and ZrO2-based supports. ChemSusChem 2015, 8, 1206–1217. [CrossRef] [PubMed] 11. Delbecq, F.; Wang, Y.; Len, C. Various carbohydrate precursors dehydration to 5-HMF in an acidic biphasic system under microwave heating using betaine as a co-catalyst. Mol. Catal. 2017, 434, 80–85. [CrossRef] 12. Delbecq, F.; Len, C. Recent advances in the microave-assisted production of hydroxymethylfurfural by hydrolysis of cellulose derivatives—A review. Molecules 2018, 23, 1973. [CrossRef][PubMed] 13. Gaset, A.; Rigal, L.; Sene, B.; Ralainirina, R. 2,5-furan dicarboxylic ester preparation. France Patent FR 2723945B1. 14. Lewkowski, J. Convenient synthesis of furan-2,5-dicarboxylic acid and its derivatives. Polish J. Chem. 2001, 75, 1943–1946. 15. Sousa, A.F.; Vilela, C.; Fonseca, A.C.; Matos, M.; Freire, C.S.R.; Gruter, G.J.M.; Coehlo, J.F.J.; Silvestre, A.J.D. Biobased polyesters and other polymers from 2,5-furandicarboxylic acid: A tribute to furan excellency. Polym. Chem. 2015, 6, 5961–5982. [CrossRef] 16. Hong, S.; Min, K.D.; Nam, B.U.; Park, O.O. High molecular weight bio furan-based co-polyesters for food packaging applications: Synthesis, characterization and solid-state polymerization. Green Chem. 2016, 18, 5142–5151. [CrossRef] 17. Storbeck, R.; Ballauff, M. Synthesis and properties of polyesters based on 2,5-furandicarboxylic acid and 1,4:3,6-dianhydrohexitols. Polymer 1993, 34, 5003–5006. [CrossRef] 18. Arnaud, S.P.; Wu, L.; Wong Chang, M.A.; Comerfod, J.W.; Farmer, T.J.; Schmid, M.; Chang, F.; Li, Z.; Mascal, M. New bio-based monomers: Tuneable polyester properties using branched diols from biomass. Faraday Discuss. 2017, 202, 61–77. [CrossRef][PubMed] 19. Konstantopoulou, M.; Terzopoulou, Z.; Nerantzaki, M.; Tsagkalias, J.; Achilias, D.S.; Bikiaris, D.N.; Exarhopoulos, S.; Papageorgiou, D.G.; Papageorgiou, G.Z. Poly(ethylene furanoate-co-ethylene terephthalate) biobased copolymers: Synthesis, thermal properties and cocrystallization behavior. Eur. Polym. J. 2017, 89, 349–366. [CrossRef] Molecules 2019, 24, 1030 14 of 15

20. Knoop, R.J.I.; Vogelzang, W.; van Haveren, J.; van Es, D.S. High molecular weight poly(ethylene-2,5-furanoate); critical aspects in synthesis and mechanical property determination. J. Polym. Sci. Part A Polym. Chem. 2013, 51, 4191–4199. [CrossRef] 21. Thiyagarajan, S.; Vogelzang, W.; Knoop, R.I.J.; Frissen, A.E.; van Haveren, J.; van Es, D.S. Biobased furandicarboxylic acids (FDCAs): Effects of isomeric substitution on polyester synthesis and properties. Green Chem. 2014, 16, 1957–1965. [CrossRef] 22. Matos, M.; Sousa, A.F.; Fonseca, A.C.; Freire, C.S.R.; Coelho, J.F.J.; Silvestre, A.J.D. A new generation of furanic copolyesters with enhanced degradability: Poly(ethylene 2,5-furandicarboxylate)-co-poly(lactic acid) copolyesters. Macromol. Chem. Phys. 2014, 215, 2175–2184. [CrossRef] 23. Morales-Huerta, J.C.; Martinez de Ilarduya, A.; Mufioz-Guerra, S. Poly(alkylene 2,5-furandicarboxylate)s (PEF and PBF) by ring opening polymerization. Polymer 2016, 87, 148–158. [CrossRef] 24. Sousa, A.F.; Matos, M.; Freire, C.S.R.; Silvestre, A.J.D.; Coehlo, J.F.J. New copolyesters derived from terephthalic and 2,5-furandicarboxylic acids: A step forward in the development of biobased polyesters. Polymer 2013, 54, 513–519. [CrossRef] 25. Wang, J.; Liu, X.; Zhang, Y.; Liu, F.; Zhu, J. Modification of poly(ethylene 2,5-furandicarboxylate) with 1,4-cyclohexanedimethylene: Influence of composition on mechanical and barrier properties. Polymer 2016, 103, 1–8. [CrossRef] 26. Gandini, A.; Sivestre, A.J.D.; Neto, C.P.; Sousa, A.F.; Gomes, M. The furan counterpart of poly(ethylene terephthalate): An alternative material based on renewable resources. J. Polym. Sci. Part A Polym. Chem. 2009, 47, 295–298. [CrossRef] 27. Gomes, M.; Gandini, A.; Silvestre, A.J.D.; Reis, B. Synthesis and characterization of poly(2,5-furan dicarboxylate)s based on a variety of diols. J. Polym. Sci. Part A Polym. Chem. 2011, 49, 3759–3768. [CrossRef] 28. Amarasekara, A.S.; Razzaq, A.; Bonham, P. Synthesis and characterization of all renewable resources based branched polyesters: Poly(2,5-furandicarboxylic acid-co-glycerol). ISRN Polym. Sci. 2013, 2013, 645169. [CrossRef] 29. Gopalakrishnan, P.; Narayan-Sarathy, S.; Ghosh, T.; Mahajan, K.; Naceur Belgaum, M. Synthesis and characterization of bio-based furanic polyesters. J. Polym. Res. 2014, 21, 340. [CrossRef] 30. Wang, J.; Liu, X.; Jia, Z.; Liu, Y.; Sun, L.; Zhu, J. Synthesis of bio-based poly(ethylene 2,5-furandicarboxylate) copolyesters: Higher glass transition temperature, better transparency, and good barrier properties. J. Polym. Sci. Part A Polym. Chem. 2017, 55, 3298–3307. [CrossRef] 31. Wu, J.; Xie, H.; Wu, L.; Li, B.G.; Dubois, P. DBU-catalyzed biobased poly(ethylene 2,5-furandicarboxylate) polyester with rapid melt crystallization: Synthesis, crystallization kinetics and melting behavior. RSC Adv. 2016, 6, 101578–101586. [CrossRef] 32. Rosenboom, J.G.; De Roo, J.; Storti, G.; Morbidelli, M. Diffusion (DOSY) 1H NMR as an alternative method for molecular weight determination of poly(ethylene furanoate) (PEF) polyesters. Macromol. Chem. Phys. 2017, 218, 1600436. [CrossRef] 33. Taguchi, Y.; Oishi, A.; Iida, H. One-step synthesis of dibutyl furandicarboxylates from galactaric acid. Chem. Lett. 2008, 37, 50–51. [CrossRef] 34. Slavko, E.; Taylor, M.S. Catalyst-controlled polycondensation of glycerol with diacyl chlorides: Linear polyesters from a trifunctional monomer. Chem. Sci. 2017, 8, 7106–7111. [CrossRef][PubMed] 35. Kumari, M.; Billamboz, M.; Leonard, E.; Len, C.; Bottcher, C.; Prasad, A.K.; Haag, R.; Sharma, S.K. Self-assembly, photoresponsive behavior and transport potential of azobenzene grafted dendronized polymeric amphiphiles. RSC Adv. 2015, 5, 48301–48310. [CrossRef] 36. Kumar, A.; Khan, A.; Malhotra, S.; Mosurkal, R.; Dhawan, A.; Pandey, M.K.; Singh, B.K.; Kumar, R.; Prasad, A.K.; Sharma, S.K.; et al. Synthesis of macromolecular systems via lipase catalyzed biocatalytic reactions: Applications and future perspectives. Chem. Soc. Rev. 2016, 45, 6855–6887. [CrossRef][PubMed] Molecules 2019, 24, 1030 15 of 15

37. Jiang, Y.; Woortman, A.J.J.; Alberda van Ekenstein, G.O.R.; Loos, K. A biocatalytic approach towards sustainable furanic-aliphatic polyesters. Polym. Chem. 2015, 6, 5198–5211. [CrossRef] 38. Van Aken, K.; Strekowski, L.; Patiny, L. Ecoscale, a semi-quantitative tool to select an organic preparation based on economical and acological parameters. Beilstein J. Org. Chem. 2006, 2, 3–9. [CrossRef][PubMed]

Sample Availability: Samples of the compounds are not available from the authors.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).