Structure-Property Relationships of Short Chain (Mixed) Cellulose Esters Synthesized in a DMSO/TMG/CO2 Switchable Solvent System.

Increasing environmental pollution and petroleum resource depletion are important indicators for the necessary and inevitable replacement of fossil-based polymeric materials with more sustainable counterparts. Hence, the development of bio-based materials from renewable resources, such as cellulose, is of great importance. Herein, we introduce a rapid and homogeneous microwave assisted synthesis of high molecular weight (59 kDa ≤ Mn ≤ 116 kDa) short chain (mixed) cellulose esters (CEs) with variable acyl side chain length (2 ≤ C ≤ 8) by using a DMSO/TMG/CO2 switchable solvent system. Accordingly, (mixed) CEs were synthesized by implementing tetramethylguanidine (TMG) into a switchable solvent system (DMSO/TMG/CO2), followed by in-depth structural characterization via IR, 1H NMR, 13C NMR, and SEC. Examination of the structure-property relationships revealed a decrease in the glass transition temperature (177 °C ≤ Tg ≤ 204 °C), an increase in surface hydrophobicity, i.e., water contact angle (WCA) (65° ≤ WCA ≤ 98°), and a decrease of Young's modulus (7.51 MPa ≤ E ≤ 13.6 MPa), with longer alkyl side chains.

Sustainable One-Pot Cellulose Dissolution and Derivatization via a Tandem Reaction in the DMSO/DBU/CO2 Switchable Solvent System.

New sustainable concepts have to be developed to overcome the increasing problems of resource availability. Cellulose derivatives with tunable material properties are promising biobased alternatives to existing petroleum-derived polymeric materials. However, the chemical modification of cellulose is very challenging, often requiring harsh conditions and complex solubilization or activation steps. More sustainable procedures toward novel cellulose derivatives are therefore of great interest. Herein, we describe a novel concept combining two approaches, (i) tandem catalysis and (ii) cellulose derivatization, by applying a single catalyst for three transformations in the DMSO/DBU/CO2 switchable solvent system. Cellulose was functionalized with four different biobased isothiocyanates, which were formed in situ via a catalytic sulfurization of isocyanides with elemental sulfur, preventing the exposure and handling of the isothiocyanates. The degree of substitution of the formed O-cellulose thiocarbamates was shown to be controllable in a range of 0.52-2.16 by varying the equivalents of the reactants. All obtained products were analyzed by ATR-IR, 1H, 13C, and 31P NMR spectroscopy as well as size exclusion chromatography, elemental analysis, differential scanning calorimetry, and thermal gravimetric analysis. Finally, the tandem reaction approach was shown to be beneficial in terms of efficiency as well as sustainability compared to a stepwise synthesis. Recycling ratios ranging from 79.1% to 95.6% were obtained for the employed components, resulting in an E-factor of 2.95 for the overall process.

Sustainable Fatty Acid Modification of Cellulose in a CO2-Based Switchable Solvent and Subsequent Thiol-Ene Modification.

Searching for more sustainable materials as an alternative to petroleum-based products is of increasing interest due to different environmental issues. Cellulose and fatty acids are two very promising candidates for biobased material design. Herein, we report a sustainable synthesis of fatty acid cellulose esters (FACEs) via transesterification of cellulose with methyl-10-undecenoate in a CO2-based switchable solvent system. FACEs with a degree of substitution between 0.70 and 1.97 were synthesized by simple variation of reaction parameters and characterized in detail. Subsequently, a FACE with a degree of substitution (DS) of 0.70 was modified via thiol-ene reaction, demonstrating an efficient and versatile method to tune the structure and properties of the new cellulose derivatives. Films were produced from each sample via solvent casting, and their mechanical properties were examined using tensile tests. Elastic moduli (E) ranging from 90 to 635 MPa and elongations at break between 2 and 23% were observed, depending on the DS of the FACE and the type of thiol employed for the modification. Finally, contact angle measurements confirmed an increase in the surface hydrophobicity (75-91°) for the thiol-ene-modified samples.

Fully Renewable Non-Isocyanate Polyurethanes via the Lossen Rearrangement.

In this work, a straightforward and efficient synthesis approach to renewable non-isocyanate polyurethanes (NIPUs) is described. For this purpose, suitable and renewable carbamate monomers, possessing two double bonds, are synthesized from hydroxamic fatty acid derivatives via the Lossen rearrangement in a one-step synthesis, and sustainable dithiols are synthesized from dialkenes derived from renewable feedstock (i.e., limonene and 1,4-cyclohexadiene). Subsequently, the comonomers are polymerized with the highly efficient thiol-ene reaction to produce NIPUs with Mn values up to 26 kg mol-1 bearing thioether linkages. The main side product of the Lossen rearrangement, a symmetric urea, can also be polymerized in the same fashion. Important in the view of sustainability, the monomer mixture can also be used directly, without separation. The obtained polymers are characterized by NMR, attenuated total reflection-infrared spectroscopy, differential scanning calorimetry, and size exclusion chromatography.

Synthesis and Encapsulation of Uniform Star-Shaped Block-Macromolecules.

Linear uniform oligomers synthesized via a two-step iterative cycle are postmodified with uniform octaethylene glycol monomethyl ether and finally coupled via azide-alkyne cycloaddition to yield uniform star-shaped block macromolecules with a mass ranging from 10 to 14 kDa. Each of the molecules is carefully characterized by NMR, electrospray ionization mass spectrometry (ESI-MS), and size exclusion chromatography (SEC) to underline their purity as well as their uniformity. The obtained star-shaped macromolecules are investigated in their ability to encapsulate dye molecules by carrying out qualitative solid-liquid phase transfer experiments.

A Practical and Efficient Synthesis of Uniform Conjugated Rod-Like Oligomers.

Herein, a more practical and efficient synthesis protocol for the preparation of uniform rod-like oligo(1,4-phenylene ethynylene)s (OPE)s is presented. Applying an iterative reaction cycle consisting of a decarboxylative coupling reaction and a saponification of an alkynyl carboxylic ester, a uniform pentamer is obtained in ten steps with 14% overall yield. The copper-free conditions prevent homocoupling until the trimer stage, resulting in a significantly easier work-up of the products. Homocoupling is observed from the tetramer stage on, but a simple variation of the work-up procedure also yields the uniform tetramer and pentamer. A thorough comparison with the commonly used and described Sonogashira approach reveals that with the new presented strategy, OPEs can be built in similar overall yield, but easier purification and in a quarter of the time. All oligomers are fully characterized by proton and carbon nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS), size-exclusion chromatography (SEC), and infrared spectroscopy (IR).

Synthesis of Passerini-3CR Polymers and Assembly into Cytocompatible Polymersomes.

The versatility of the Passerini three component reaction (Passerini-3CR) is herein exploited for the synthesis of an amphiphilic diblock copolymer, which self-assembles into polymersomes. Carboxy-functionalized poly(ethylene glycol) methyl ether is reacted with AB-type bifunctional monomers and tert-butyl isocyanide in a single process via Passerini-3CR. The resultant diblock copolymer (P1) is obtained in good yield and molar mass dispersity and is well tolerated in model cell lines. The Passerini-3CR versatility and reproducibility are shown by the synthesis of P2, P3, and P4 copolymers. The ability of the Passerini P1 polymersomes to incorporate hydrophilic molecules is verified by loading doxorubicin hydrochloride in P1DOX polymersomes. The flexibility of the synthesis is further demonstrated by simple post-functionalization with a dye, Cyanine-5 (Cy5). The obtained P1-Cy5 polymersomes rapidly internalize in 2D cell monolayers and penetrate deep into 3D spheroids of MDA-MB-231 triple-negative breast cancer cells. P1-Cy5 polymersomes injected systemically in healthy mice are well tolerated and no visible adverse effects are seen under the conditions tested. These data demonstrate that new, biodegradable, biocompatible polymersomes having properties suitable for future use in drug delivery can be easily synthesized by the Passerini-3CR.

Fatty Acids and their Derivatives as Renewable Platform Molecules for the Chemical Industry.

Oils and fats of vegetable and animal origin remain an important renewable feedstock for the chemical industry. Their industrial use has increased during the last 10 years from 31 to 51 million tonnes annually. Remarkable achievements made in the field of oleochemistry in this timeframe are summarized herein, including the reduction of fatty esters to ethers, the selective oxidation and oxidative cleavage of C-C double bonds, the synthesis of alkyl-branched fatty compounds, the isomerizing hydroformylation and alkoxycarbonylation, and olefin metathesis. The use of oleochemicals for the synthesis of a great variety of polymeric materials has increased tremendously, too. In addition to lipases and phospholipases, other enzymes have found their way into biocatalytic oleochemistry. Important achievements have also generated new oil qualities in existing crop plants or by using microorganisms optimized by metabolic engineering.

Modification of Starch via the Biginelli Multicomponent Reaction.

An efficient and straightforward modification of starch using renewable and commercially available aromatic aldehydes (benzaldehyde, vanillin, and p-anisaldehyde) and urea via the Biginelli multicomponent reaction is reported in this work. First, starch acetoacetate (SAA) with a degree of substitution ranging from 1.4 to 2.5, depending on the reaction time or the molar ratio of reactants, is prepared. SAA is then modified with different aromatic aldehydes and urea via the Biginelli reaction. The modified products are characterized by ATR-IR, NMR, and gel permeation chromatography (GPC). The processability of the products is also investigated using a hot press instrument, revealing that glycerol is a suitable and renewable plasticizer for the Biginelli products.

Progress Toward Sustainable Reversible Deactivation Radical Polymerization.

The recent focus of media and governments on renewability, green chemistry, and circular economy has led to a surge in the synthesis of renewable monomers and polymers. In this review, focussing on renewable monomers for reversible deactivation radical polymerizations (RDRP), it is highlighted that for the majority of the monomers and polymers reported, the claim to renewability is not always accurate. By closely examining the sustainability of synthetic routes and the renewability of starting materials, fully renewable monomers are identified and discussed in terms of sustainability, polymerization behavior, and properties obtained after polymerization. The holistic discussion considering the overall preparation process of polymers, that is, monomer syntheses, origin of starting materials, solvents used, the type of RDRP technique utilized, and the purification method, allows to highlight certain topics which need to be addressed in order to progress toward not only (partially) renewable, but sustainable monomers and polymers using RDRPs.

Biocompatible Unimolecular Micelles Obtained via the Passerini Reaction as Versatile Nanocarriers for Potential Medical Applications.

A Passerini three-component polymerization was performed for the synthesis of amphiphilic star-shaped block copolymers with hydrophobic cores and hydrophilic coronae. The degree of polymerization of the hydrophobic core was varied from 5 to 10 repeating units, and the side chain ends were conjugated by performing a Passerini-3CR with PEG-isocyanide and PEG-aldehyde (950 g/mol). The resulting amphiphilic star-shaped block copolymers contained thioether groups, which could be oxidized to sulfones in order to further tune the polarity of the polymer chains. The ability of the amphiphilic copolymers to act as unimolecular micellar encapsulants was tested with the water-insoluble dye Orange II, the water-soluble dye Para Red and the macrolide antibiotic azithromycin. The results showed that the new copolymers were able to retain drug cargo at pH levels corresponding to circulating blood and selectively release therapeutically effective doses of antibiotic as measured by bacterial cell kill. The polymers were also well-tolerated by differentiated THP-1 macrophages in the absence of encapsulated drugs.

Plant-Oil-Based Polyamides and Polyurethanes: Toward Sustainable Nitrogen-Containing Thermoplastic Materials.

Plant oils and their derived fatty acids are a highly valuable renewable resource for polymer science. In this review, the use of this renewable resource for the synthesis of nitrogen-containing step-growth polymers, that is, polyamides and polyurethanes, is described. The focus is on the accessible structures of monomers and polymers and thus also the obtainable polymer properties. More importantly, the sustainability of the approaches is discussed and compared to each other where possible, also giving suggestions for future developments.

Polymacrocycles Derived via Ugi Multi-Component Reactions.

The synthesis of macrocycles based on the Ugi-4CR has been thoroughly explored by Wessjohann and coworkers, while polymerizations utilizing the Ugi-4CR are already patented by Ugi and recently studied more in detail, developing a new trend in polymer chemistry. Here, the combination of both, that is, the synthesis of polymacrocycles, is demonstrated. As diverse functional groups can be easily introduced in a macrocycle via Ugi-4CR, a straightforward design of polymacrocycles is achieved in a two-step procedure. First, the Ugi-4CR of 10-undecenoic acid, a diamine, a diisocyanide, and an aldehyde results in diversely substituted macrocycles having two terminal double bonds. Subsequently, these macrocycles are polymerized by ADMET (acyclic diene metathesis) or thiol-ene polymerization to generate polymacrocycles with potential application in coordination chemistry as, for example, sensors, filters, or phase-transfer catalysts. Moreover, the setup of the literature-known Ugi macrocyclization is simplified by systematic reaction screening.

A Combined Photochemical and Multicomponent Reaction Approach to Precision Oligomers.

We introduce the convergent synthesis of linear monodisperse sequence-defined oligomers through a unique approach, combining the Passerini three-component reaction (P-3CR) and a Diels-Alder (DA) reaction based on photocaged dienes. A set of oligomers is prepared resting on a Passerini linker unit carrying an isocyano group for chain extension by P-3CR and a maleimide moiety for photoenol conjugation enabling a modular approach for chain growth. Monodisperse oligomers are accessible in a stepwise fashion by switching between both reaction types. Employing sebacic acid as a core unit allows the synthesis of a library of symmetric sequence-defined oligomers. The oligomers consist of alternating P-3CR and photoblocks with molecular weights up to 3532.16 g mol-1 , demonstrating the successful switching from P-3CR to photoenol conjugation. In-depth characterization was carried out including size-exclusion chromatography (SEC), high-resolution electrospray ionization mass spectrometry (ESI-MS) and NMR spectroscopy, evidencing the monodisperse nature of the precision oligomers.

Renewable Polyethers via GaBr3 -Catalyzed Reduction of Polyesters.

Herein, a novel approach is reported for the synthesis of medium- and long-chain aliphatic polyethers 2 based on the GaBr3 -catalysed reduction of polyesters 1 with TMDS as the reducing agent. Thus, various linear and branched aliphatic polyesters 1 were prepared and systematically investigated for this reduction strategy, demonstrating the applicability and versatility of this new polyether synthesis protocol. Medium- and long-chain chain polyethers were obtained from the respective polyesters without or with minor chain degradation, whereas short-chain polyesters, such as poly-l-lactide 1 i and poly[(R)-3-hydroxybutanoate] 1 j, showed major chain degradation. In this way, previously unavailable and uncommon polyethers were obtained and studied.

Combining Two Methods of Sequence Definition in a Convergent Approach: Scalable Synthesis of Highly Defined and Multifunctionalized Macromolecules.

The straightforward convergent synthesis of sequence-defined and multifunctionalized macromolecules is described herein. The first combination of two efficient approaches for the synthesis of sequence-defined macromolecules is reported: thiolactone chemistry and the Passerini three-component reaction (P-3CR). The thiolactone moiety was used as protecting group for the thiol, allowing the synthesis of a library of sequence-defined α,ω-functionalized building blocks. These building blocks were subsequently efficiently coupled to oligomers with carboxylic acid functionalities in a P-3CR. Thus, larger oligomers with molecular weights of up to 4629.73 g mol-1 were obtained in gram quantities in a convergent approach along with the introduction of independently selectable side chains (up to 15), thus clearly demonstrating the high versatility and the efficiency of the reported approach.

Recent Progress in the Design of Monodisperse, Sequence-Defined Macromolecules.

This review describes different synthetic strategies towards sequence-defined, monodisperse macromolecules, which are built up by iterative approaches and lead to linear non-natural polymer structures. The review is divided in three parts: solution phase-, solid phase-, and fluorous- and polymer-tethered approaches. Moreover, synthesis procedures leading to conjugated and non-conjugated macromolecules are considered and discussed in the respective sections. A major focus in the evaluation is the applicability of the different approaches in polymer chemistry. In this context, simple procedures for monomer and oligomer synthesis, overall yields, scalability, purity of the oligomers, and the achievable level of control (side-chains, backbone, stereochemistry) are important benchmarks.

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions.

The Biginelli reaction was combined with the Passerini reaction for the first time in a sequential multicomponent tandem reaction approach. After evaluation of all possible linker components and a suitable solvent system, highly functionalized dihydropyrimidone-α-acyloxycarboxamide compounds were obtained in good to excellent yields. In a first reaction step, different 3,4-dihydropyrimidin-2(1H)-one acids were synthesized, isolated and fully characterized. These products were subsequently used in a Passerini reaction utilizing a dichloromethane/dimethyl sulfoxide solvent mixture. By variation of the components in both multicomponent reactions, a large number of structurally diverse compounds could be synthesized. In addition, a one-pot Biginelli-Passerini tandem reaction was demonstrated. All products were carefully characterized via 1D and 2D NMR as well as IR and HRMS.

Renewability is not Enough: Recent Advances in the Sustainable Synthesis of Biomass-Derived Monomers and Polymers.

Taking advantage of the structural diversity of different biomass resources, recent efforts were directed towards the synthesis of renewable monomers and polymers, either for the substitution of petroleum-based resources or for the design of novel polymers. Not only the use of biomass, but also the development of sustainable chemical approaches is a crucial aspect for the production of sustainable materials. This review discusses the recent examples of chemical modifications and polymerizations of abundant biomass resources with a clear focus on the sustainability of the described processes. Topics such as synthetic methodology, catalysis, and development of new solvent systems or greener alternative reagents are addressed. The chemistry of vegetable oil derivatives, terpenes, lignin, carbohydrates, and sugar-based platform chemicals was selected to highlight the trends in the active field of a sustainable use of renewable resources.

High Glass Transition Temperature Renewable Polymers via Biginelli Multicomponent Polymerization.

A novel and straightforward one-pot multicomponent polycondensation method was established in this work. The Biginelli reaction is a versatile multicomponent reaction of an aldehyde, a ß-ketoester (acetoacetate) and urea, which can all be obtained from renewable resources, yielding diversely substituted 3,4-dihydropyrimidin-2(1H)-ones (DHMPs). In this study, renewable diacetoacetate monomers with different spacer chain lengths (C3, C6, C10, C20) were prepared via simple transesterification of renewable diols and commercial acetoacetates. The diacetoacetate monomers were then reacted with renewable dialdehydes, i.e., terephthalaldehyde and divanillin in a Biginelli type step-growth polymerization. The obtained DHMP polymers (polyDHMPs) displayed high molar masses, high glass transition temperatures (Tg) up to 203 °C and good thermal stability (Td5%) of 280 °C. The Tg of the polyDHMPs could be tuned by variation of the structure of the dialdehyde or the diacetoacetate component.