Phosphorylation of bio-based compounds: the state of the art Nicolas Illy, Maxence Fache, Raphaël Ménard, Claire Negrell, Sylvain Caillol, Ghislain David To cite this version: Nicolas Illy, Maxence Fache, Raphaël Ménard, Claire Negrell, Sylvain Caillol, et al.. Phosphorylation of bio-based compounds: the state of the art. Polymer Chemistry, Royal Society of Chemistry - RSC, 2015, 6 (35), pp.6257-6291. 10.1039/c5py00812c. hal-01186950 HAL Id: hal-01186950 https://hal.archives-ouvertes.fr/hal-01186950 Submitted on 28 Sep 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 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 Davidc Over the last few years more and more papers have been devoted to phosphorus-containing polymers, mainly due to their fire resistance, excellent chelating and metal-adhesion properties. 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 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. 1 Introduction The use of phosphorus in technical applications is primarily intended for use in polymeric materials to improve the electronic conduction, fire-retardancy, lubrication, adhesion properties and anti-corrosion. In these applications, phosphorus advantageously replaces hazardous substances historically used in these applications, such as chromium VI derivatives for anti-corrosion or halogen compounds for fire-retardancy. Replacing these substances is a social and industrial challenge; indeed chromium VI derivatives or halogen compounds used in these applications are generally carcinogenic, mutagenic and reprotoxic (CMR) substances that regulations tend to ban (European Regulation EC/2000/60)). Recently developed halogen-free phosphorus-containing polymers can be employed for a wide range of technological applications, such as for example scaffolds in regenerative medicine applications or for drug delivery.1 Compared to the use of phosphorylated additives, the use of polymeric backbones reduces toxic bioaccumulation and minimizes losses due to diffusion and washing process. In addition, reuse and recycling become possible. Nevertheless, the replacement of petro-based chemicals and materials is currently challenging both research and industry.2 Sustainability, reduction of environmental impacts and green chemistry are increasingly guiding the development of the next generation of materials. The use of bio-based polymer matrices will allow the reduction of environmental impacts by using renewable carbon and by achieving more easily biodegradable or reusable materials. It will also permit the valorization of numerous by-products and wastes of different activities.3 In addition, the functionalization with phosphorus-containing-moieties modifies the properties of bio-based compounds, such as water-solubility, which enables an easier processing and makes them more competitive with petro-based derivatives. To our knowledge, even if literature reports some reviews on phosphorus monomers and polymers1, 4-12 there is no review on the use of phosphorus in biobased polymers. 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. Numerous strategies have been developed to introduce phosphorus-containing moieties. Nevertheless, these strategies have to be adjusted to bio-based compounds which significantly differ 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; more rarely amino groups (chitosan), carboxylic acid or aldehyde groups (lignin). On the other hand, on the same macromolecule, these moieties are often abundant and have similar reactivities which may be problematic in terms of functionalization degree and regioselectivity. In the first part, the more frequent strategies for the introduction of 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. Scheme 1 Phosphorylation of hydroxy functions with three ways : A-Esterification with H3PO4 B- Phosphorylation with P4O10 and C-Reaction of Williamson reaction (R = aliphatic or aromatic groups and R’ = chloro, alkyl, aryl or oxyalkyl groups). 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 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 review, we will focus on the methods adapted to functions present on the renewable molecules. These available functions are hydroxy and amine groups in polysaccharides, carboxylic, hydroxy, aldehyde groups in biophenols or double bonds in triglycerides, principally. 2.1 Phosphorylation of R-OH On bio-based products, two types of hydroxy groups are available: the aliphatic OH such as in the cellulose and aromatic OH such as in the biophenols (lignin derivates). The different synthesis described after are adapted to the two types of hydroxy functions. The easiest method to introduce phosphorus-containing function on hydroxy groups was by esterification reactions with H3PO3 or H3PO4 : the phosphorus can be covalently attached to the renewable molecule chain via a reaction of hydroxy groups to give: phosphate groups R–O–P(O)(OH)2, phosphite groups R–O–P(OH)2 or phosphonic acid group R-P(O)(OH)2…. H3PO3 and these derivatives containing mobile hydrogen atoms directly attached to phosphor are in tautomeric equilibrium and allow to obtain phosphonated compounds. From the perspective of green chemistry, the direct catalytic condensation of equimolar amounts of phosphoric acid (H3PO4) and alcohols is attractive for the synthesis of phosphoric acid monoesters (Scheme 1A). The classical method is the dehydrative condensation promoted by a catalyst under reflux condition in polar solvents.14 A derivative method uses (poly)phosphoric acid salts to introduce charged phosphonic function via OH containing organic compounds.15 The phosphorylation reactions of OH–containing organic molecules with phosphorus pentoxide (P4O10) with its common name derived from its empirical formula P2O5 is another classical method. It is also an esterification reaction and this reagent works as an anhydride of phosphoric acid (Scheme 1B). The mechanism16 of this reaction includes the 4 steps with a large excess of alcohol (4 equivalents) to have the better efficiency of P4O10. The combined use of P2O5 and H3PO4, allows obtaining highly phosphorylated sugar derivatives.17 Phosphorus oxychloride, dialkyl chlorophosphonates or diphenylphosphinic chloride are the most employed phosphorylating agents for OH-containing organic compounds, this reaction is a derivate of Williamson reaction (Scheme 1C). The use of POCl3 was first proposed in 1857. The reaction of alcohols with POCl3 in the presence of water and pyridine as a base provides phosphate monoesters along with pyridine hydrochloride as a by-product.18 Since POCl3 is very reactive, phosphate diesters and triesters could be produced with an adapted stoichiometry. The use of phosphorochloridates provides an organic soluble phosphate triesters. Generally, these phosphorylations with trivalent or pentavalent phosphorus reagents proceed only on reactive hydroxy group and allowed to obtain P-O bond. The use of trivalent phosphorus reagent like phosphorochloridites, is possible despite the sensitivity of moisture. When the reaction