Polymer Chemistry Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/polymers Page 1 of 37 PleasePolymer do not Chemistryadjust margins Polymer Chemistry Review Phosphorylation of bio-based compounds: state of the art Nicolas Illy,a,b,* Maxence Fache,c Raphaël Ménard,c Claire Negrell,c Sylvain Caillol,c and Ghislain Received 00th January 20xx, Davidc Accepted 00th January 20xx Over the last few years more and more papers have been devoted to phosphorus-containing DOI: 10.1039/x0xx00000x polymers, mainly due to their fire resistance, excellent chelating and metal-adhesion properties. www.rsc.org/ Nevertheless, sustainability, reduction of environmental impacts and green chemistry are increasingly guiding the development of the next generation of materials. The use of bio-based Manuscript polymer matrices might allow the reduction of environmental impacts by using renewable carbon and by achieving more easily biodegradable or reusable materials. The aim of this review is to present both fundamental and applied research of phosphorylation of renewable resources, through reactions on natural occurring functions, and their use in biobased polymer chemistry and applications. In the first part, different strategies for the introduction of phosphorus- containing functions on organic backbones are described. In the following sections, the main families of chemicals based on renewable resources are covered: namely polysaccharides (cellulose, chitosan, starch, dextran...), biophenols (lignins, biobased phenolic compounds, cardanol...), triglycerides (oils, glycerol) and hydroxy acid compounds. currently challenging both research and industry.2 Sustainability, reduction of environmental impacts and green 1 Introduction chemistry are increasingly guiding the development of the next The use of phosphorus in technical applications is primarily generation of materials. The use of bio-based polymer Accepted intended for use in polymeric materials to improve the matrices will allow the reduction of environmental impacts by electronic conduction, fire-retardancy, lubrication, adhesion using renewable carbon and by achieving more easily properties and anti-corrosion. In these applications, biodegradable or reusable materials. It will also permit the phosphorus advantageously replaces hazardous substances valorization of numerous by-products and wastes of different historically used in these applications, such as chromium VI activities.3 In addition, the functionalization with phosphorus- derivatives for anti-corrosion or halogen compounds for fire- containing-moieties modifies the properties of bio-based retardancy. Replacing these substances is a social and compounds, such as water-solubility, which enables an easier industrial challenge; indeed chromium VI derivatives or processing and makes them more competitive with petro- halogen compounds used in these applications are generally based derivatives. carcinogenic, mutagenic and reprotoxic (CMR) substances that To our knowledge, even if literature reports some reviews regulations tend to ban (European Regulation EC/2000/60)). on phosphorus monomers and polymers1, 4-12 there is no Recently developed halogen-free phosphorus-containing review on the use of phosphorus in biobased polymers. The polymers can be employed for a wide range of technological aim of this review is to present both fundamental and applied applications, such as for example scaffolds in regenerative research of phosphorylation of renewable resources, through Chemistry 1 medicine applications or for drug delivery. reactions on natural occurring functions, and their use in Compared to the use of phosphorylated additives, the use biobased polymer chemistry and applications. Numerous of polymeric backbones reduces toxic bioaccumulation and strategies have been developed to introduce phosphorus- minimizes losses due to diffusion and washing process. In containing moieties. Nevertheless, these strategies have to be addition, reuse and recycling become possible. Nevertheless, adjusted to bio-based compounds which significantly differ the replacement of petro-based chemicals and materials is from regular chemicals. Biopolymers contain a low diversity of functional groups with often a high degree of oxidation: mainly hydroxy and phenolic hydroxy groups or unsaturated groups; a. Sorbonne Universités, UPMC Univ Paris 06, UMR 8232, IPCM, F-75005, Paris, more rarely amino groups (chitosan), carboxylic acid or France. b. CNRS, UMR 8232, IPCM, F-75005, Paris, France.. aldehyde groups (lignin). On the other hand, on the same c. Institut Charles Gerhardt Montpellier UMR 5353 - Equipe Ingénierie et macromolecule, these moieties are often abundant and have Architectures Macromoléculaires, Ecole Nationale Supérieure de Chimie de Polymer Montpellier, 34296 Montpellier, CEDEX 5, France. similar reactivities which may be problematic in terms of This journal is © The Royal Society of Chemistry 20xx Polym. Chem., 2015, 00, 1-3 | 1 Please do not adjust margins PleasePolymer do not Chemistryadjust margins Page 2 of 37 REVIEW Polymer Chemistry functionalization degree and regioselectivity. In the first part, efficiency of P4O10. The combined use of P2O5 and H3PO4, the more frequent strategies for the introduction of allows obtaining highly phosphorylated sugar derivatives.17 phosphorus-containing functions on bio-based backbones are described. The following parts provide precise and complete information on the phosphorylation of a specific family of biopolymers (i.e. polysaccharides, biophenols, triglycerides and hydroxy acid compounds). The end of each part is devoted to the properties of the phosphorylated compounds and their potential applications. 2 Common routes to functional phosphoric acids or esters on bio-based products. Different strategies for the introduction of phosphoric function on organic bio-based backbones are described hereafter. From a synthetic chemistry point of view, a wide range of methodologies for the incorporation of phosphorus have been Manuscript discovered and reported as early as in 1898.13 Since many advances have been made, this will allow for the introduction of phosphorus directly into different organic molecules. In this Scheme 1 Phosphorylation of hydroxy functions with review, we will focus on the methods adapted to functions three ways : A-Esterification with H PO B- present on the renewable molecules. These available functions 3 4 Phosphorylation with P O and C-Reaction of Williamson are hydroxy and amine groups in polysaccharides, carboxylic, 4 10 reaction (R = aliphatic or aromatic groups and R’ = chloro, hydroxy, aldehyde groups in biophenols or double bonds in alkyl, aryl or oxyalkyl groups). triglycerides, principally. 2.1 Phosphorylation of R-OH Phosphorus oxychloride, dialkyl chlorophosphonates or On bio-based products, two types of hydroxy groups are diphenylphosphinic chloride are the most employed available: the aliphatic OH such as in the cellulose and phosphorylating agents for OH-containing organic compounds, aromatic OH such as in the biophenols (lignin derivates). The this reaction is a derivate of Williamson reaction (Scheme 1C). Accepted different synthesis described after are adapted to the two The use of POCl3 was first proposed in 1857. The reaction of types of hydroxy functions. The easiest method to introduce alcohols with POCl3 in the presence of water and pyridine as a phosphorus-containing function on hydroxy groups was by base provides phosphate monoesters along with pyridine 18 esterification reactions with H3PO3 or H3PO4 : the phosphorus hydrochloride as a by-product. Since POCl3 is very reactive, can be covalently attached to the renewable molecule chain phosphate diesters and triesters could be produced with an via a reaction of hydroxy groups to give: phosphate groups R– adapted stoichiometry. The use of phosphorochloridates O–P(O)(OH)2, phosphite groups R–O–P(OH)2 or phosphonic provides an organic soluble phosphate triesters. acid group R-P(O)(OH)2…. H3PO3 and these derivatives Generally, these phosphorylations with trivalent or containing mobile hydrogen atoms directly attached to pentavalent phosphorus reagents proceed only on reactive phosphor are in tautomeric equilibrium and allow to obtain hydroxy group and allowed to obtain P-O bond. The use of phosphonated compounds. trivalent phosphorus reagent like phosphorochloridites, is From the perspective of green chemistry, the direct possible despite the sensitivity of moisture. When the reaction catalytic condensation of equimolar amounts of phosphoric