Polyphosphoesters Polyphosphoesters Chemistry and Application Kolio Dimov Troev Institute of Polymers Bulgarian Academy of Sciences Bulgaria AMSTERDAM BOSTON HEIDELBERG LONDON NEW YORK OXFORD ● ● ● ● ● PARIS SAN DIEGO SAN FRANCISCO SINGAPORE SYDNEY TOKYO ● ● ● ● ● Elsevier 32 Jamestown Road, London NW1 7BY 225 Wyman Street, Waltham, MA 02451, USA First edition 2012 Copyright r 2012 Elsevier Inc All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangement with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN: 978-0-12-416036-1 For information on all Elsevier publications visit our website at elsevierdirect.com This book has been manufactured using Print On Demand technology Each copy is produced to order and is limited to black ink The online version of this book will show color figures where appropriate Preface Phosphorus chemistry has contributed in various ways to the present progress in biology, biochemistry, medicine, and industry, providing new, highly specified materials Phosphorus is a key element in polymer chemistry Polymeric materials have the potential to simulate the mechanical and chemical behavior of biological tissues better than metals or ceramics The contribution of phosphorus chemistry in this area is significant The discovery in the early 1950s that the incorporation of phosphorus into a polymer’s backbone gives it flame-retardant properties sparked great interest in phosphorus polymer chemistry However, because of the high cost of synthesizing these polymers in comparison to carbon analogues, their low molecular weight, and their perceived hydrolytic instability, research interests have faded since the 1960s The versatility of the phosphorus atom was exploited to be synthesized into a wide range of polymers The most important feature of phosphorus chemistry is the methods of synthesis of polymers that allow the main chain and the side group to be varied over a very broad range Different main chain and side groups generate different properties such that the characteristics may vary from those of linear to cross-linked, from water-soluble to hydrophobic polymers, and from bioinert to bioactive materials This is crucially important for developing new multifunctional materials Recently, organophosphorus polymers, especially polyphosphoesters with phosphoester bonds (aPaOaCa) in the main chain, have regained our interest due to these properties: ● ● ● ● ● ● ● ● Excellent thermal stability Fire resistance Excellent adhesion to glass and metals Excellent binding properties High refractivity (invisible cements for glass) Good resistance to abrasion High resistance to acids Attractive mechanical properties Among these polymers, polyphosphates, structurally related to the natural biopolymers, play a key role as a new class of polymers with the following properties: ● ● ● ● ● Biodegradable Biocompatible Thermoresponsive Nontoxic Water soluble x Preface These properties can be modified to match a specific application as a carrier of drugs and genes In the last 10 years, especially, poly(alkylene H-phosphonate)s and poly(alkylene phosphate)s are considered to be one of the most promising polymers for medicine and pharmacy A number of papers were published devoted to the application of these polymers as carriers of drugs and genes The main goal of this book is to provide knowledge for the advantageous properties of polyphosphoesters They are polyesters of the corresponding phosphorus acids There are five types of organophosphorus acids; three of them are of the pentavalent phosphorus and two of the tervalent phosphorus atoms In this book, their chemistry and application are discussed in detail O O HO- P -OH RO - P - OR H H H-phosphonic acid Esters: H-phosphonates O Polyesters: Poly(alkylene H-phosphonate)s O - P- O - R' H O O HO- P -OH RO- P -OR OH Phosphoric acid n OR Esters: Phosphates O Polyesters: Poly[alkylene(arylene) phosphate]s O - P - O - R' OR n O O HO- P -OH RO - P - OR R(Ar) Alkyl(aryl) phosphonic acid R Esters: Alkyl or arylphosphonates O Polyesters: Poly[alkylene(arylene) alkyl or arylphosphonate]s O - P - O - R' R(Ar) n Preface xi In polyesters of phosphorous and phosphonous acids, the phosphorus atom is a tervalent: HO- P -OH OH Phosphorous acid Polyesters: Poly(alkylene phosphites) RO- P -OR OR Esters: phosphites O - P - O - R' OR HO- P -OH R Phosphonous acid Polyesters: Poly(alkylene phosphonites) n RO- P -OR R Esters: Phosphonites O - P - O - R' R n With regard to synthetics, polyesters of the pentavalent phosphorus are most important Acknowledgment I take a great pleasure in gratefully acknowledging Tokyo University of Science for providing the access to all literature references needed The support of Action CM08902 of the European Cooperation in Science and Technology (COST) Framework Programme is also acknowledged I am heartily thankful to my wife, Krassimira, who was very supportive in my efforts to write and complete the book About the Author Kolio Dimov Troev was born in Rupkite, in the district of Chirpan, Bulgaria, 1944 He did his undergraduate work at the Higher Institute of Chemical Technology, Sofia, and received his doctorate in the field of organophosphorus chemistry in 1974 from the Institute of Organic Chemistry, Bulgarian Academy of Sciences, with Prof Georgy Borissov In 1985, he received the scientific degree Doctor of Science from the Institute of Polymers, where he worked In 1988, he became Professor of Chemistry at the same Institute Since 1989, he has been head of the laboratory “Phosphorus-containing monomers and polymers,” which he established in 1989 His research interests are in the areas of organophosphorus chemistry, especially esters of H-phosphonic acid; aminophosphonates; biodegradable, biocompatible phosphoruscontaining polymers; polymer conjugates; and drug delivery systems He has taught in the United States (Marquette University, Tulane University), Japan (Tokyo Institute of Technology, University of Tokyo, Tohoku University, Tokyo University of Science), and Germany (Duăsseldorf University) He is an author of more than 125 papers in this field published in the Phosphorus, Sulfur, Silicon and Related Elements; Heteroatom Chemistry; Journal of American Chemical Society; European Polymer Journal; Polymer; Bioorganic & Medicinal Chemistry; Journal of Medicinal Chemistry; Macromolecular Rapid Communication; Polymer Degradation and Stability; Journal of Polymer Science, Part A: Polymer Chemistry; European Journal of Medicinal Chemistry; Amino Acids; and Tetrahedron Letters In October 2006, Elsevier published his book Chemistry and Application of H-phosphonates Since 2003, he has been director of the Institute of Polymers, Bulgarian Academy of Sciences He and his wife, Krassimira, have a daughter, who is a notary public in British Columbia, Canada, and a son, who is an economist Poly(alkylene H-phosphonate)s Poly(alkylene H-phosphonate)s are polyesters of the H-phosphonic acid O HO P OH H They are one of the most interesting classes of polyphosphoesters because both the polymer backbone and phosphorus substituents can be modified O RO P O O R1 O H P H O O R1 O n P OR H The most important feature of poly(alkylene H-phosphonate) chemistry is the methods of synthesis that allow the main chain and the side group to be varied over a very broad range Different main chain and side groups generate different properties such that the characteristics may vary from those of linear to crosslinked, from water soluble to hydrophobic polymers, and from bioinert to bioactive materials In particular, these polymers might possess potential as a new class of degradable biomaterials whose properties can be modified to match a specific application Polymeric materials have the potential to simulate the mechanical and chemical behavior of biological tissues better than metals or ceramics Poly(alkylene H-phosphonate)s are particularly interesting due to the fact that the PaH group in the repeating unit is highly reactive and permits a number of chemical transformations, proceeding in mild conditions with practically quantitative yield Poly(alkylene H-phosphonate)s are a versatile starting material for preparation of various polymer derivatives Oxidative chlorination of these polymers using chlorine, AthertonÀTodd reaction conditions, copper dichloride, or trichloroacetic acid in carbon tetrachloride followed by reaction with alcohols and amines yields the corresponding polymeric phosphate esters or amides Oxidation with N2O4 furnishes poly(hydroxyalkylene phosphate)s (Scheme 1.1) The interest in the chemistry and application of poly(alkylene H-phosphonate)s has dramatically increased over recent years because they show promise as new biodegradable, water-soluble, polymerÀdrug carriers Polyphosphoesters DOI: 10.1016/B978-0-12-416036-1.00001-2 © 2012 Elsevier Inc All rights reserved Polyphosphoesters O _ O - P - O - R_ _ O - P - O - R_ O _O - P - O - R O _ O - P - O - R_ Cl CH(OR')2 CH2OH OH O _O - P - O - R _ _ O - P - O - R_ _O - P - O - R CH2NHR' H O O O O _O - P - O - R O-P-O-R OR1 OR2 Cl O O O O-P-O-R O R1- CH- NHR2 _O - P - O - R O O-P-O-R O CH C _ O - P - O - R_ O O O-P-O-R _ OR2 NHR' _ O - P - O - R _ _O - P - O - R _ O _ O R1 O _ O - P - O - R_ O Scheme 1.1 Chemical transformations of the PaH group in the repeating unit of poly (alkylene H-phosphonate)s METHODS FOR PREPARATION A number of synthetic methods have been explored for the synthesis of these polymers, including ring-opening, bulk, and enzymatic polymerization Bulk polycondensation is often used as a preferred method for large-scale production of poly(alkylene H-phosphonate)s The advantages of the polycondensation method are the possibility of preparing polymers with different structure and composition, the short reaction time, minimal purification steps, and feasibility for scale-up For laboratory purposes, poly(alkylene H-phosphonate)s can be obtained by other methods 1.1 Polymerization of Cyclic H-phosphonates The ring-opening polymerization of five- (phospholane) and six-membered (phosphorinane) cyclic H-phosphonates furnished high molecular poly(alkylene H-phosphonate)s O O (XCY)m P n O m = or X O P O (C)m O H H Y n 314 Polyphosphoesters 20 21 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A Gribova, V K Shitikov, Izv Akad Nauk SSSR Otd Khim Nauki, 210 (1958) V N Odnoralova, G I Kudryavtsev, Zh Vses Khim Obshchestvam D I Mendeleeva, 6, 479 (1961) S Kobayashi, T Y Chow, H Kawabata, T Saegusa, Polym Bull., 16, 269 (1986) M L Nielsen, US Pat 3,354,242 (1967) A D Toy, US Pat 2,435,252 (1948) A D Toy, US Pat 2,572,076 (1951) H Zenftman, R McGilivray, Br Pat 653,489 (1951); US Pat 2,636,020 (1953) H W Coover, M A McCall, US Pat 2,716,100 (1955) H W Coover, US Pat 2,743,258 (1956) H W Coover, M A McCall, US Pat 2,716,101 (1955) I Thomas, US Pat 3,326,852 (1967) Y Masai, Y Kato, N Fukui, US Pat 3,719,717 (1973) G Desitter, G Viviant, Br Pat 1,411,211 (1975) 316 Polyphosphoesters 87 B C Gill, US Pat 5,393,621 (1995) 88 H Q Mao, K W Leong, Z Zhao, W Dang, J P English, D P Nowotnik, US Pat 6,485,737 (2002) 89 B G Dixon, R S Morris, S Dallek, J Power Sources, 138, 274 (2004) 90 A J Conix, Belg Pat 610953 (1965) 91 J R Caldwell, W J Jackson, US Pat 3,378,523 (1963) Appendix General procedure for the preparation of cyclic phosphite esters [D C Ayres, H N Rydon, J Chem Soc., 1109 (1957)] Triphenyl phosphite (155 g, 0.5 mol) was vigorously stirred on the stem-bath with ethyle glycol (31 g, 0.5 mol) in which sodium (0.2 g, 0.01 mol) had been dissolved Heating and stirring were continued for B2 h after the mixture had become homogeneous Distillation afforded 2-phenoxy-1,3,2-dioxaphospholane (55.0 g, 60%, BP 70À76 C/0.2 mmHg) General procedure for the preparation of cyclic esters of phenylphosphonic acid [A D Toy, US Pat 2,382,622 (1945)] 58.5 g (0.3 mol) of phenyl phosphonic dichloride and 19.5 g of (0.31 mol) ethylene glycol were mixed in a reaction vessel under vacuum while maintaining a temperature of not over B25 C After B85À95% of hydrogen chloride was removed, the heat was raised to distill off the excess ethylene glycol, and the reaction product was then purified by distillation Yield 75%, BP 210 C/6À7 mmHg When cooled, the 2-phenyl-2-oxo-1,3,2-dioxaphospholane forms a hygroscopic, white, crystalline solid The same procedure is used for the preparation of the 2-phenyl-2-oxo-1,3,2-dioxaphosphorinane with yield 67% (BP 212À214 C/7.5 mmHg) and 4,5-dimethyl-2-phenyl-2-oxo1,3,2-dioxaphospholane with yield 78.6% (BP 210À215 C/15 mmHg) General procedure for the preparation of cyclic esters of alkyl or phenylphosphonic acid [V V Korshak, I A Gribova, M A Andreeva, Izv Akad Nauk SSSR Otd Khim Nauki, 5, 631 (1957)] Syntheses were performed in a three-necked flask in argon atmosphere to the solution of 12.4 g (0.2 mol) ethylene glycol, 40.4 g (0.4 mol) triethylamine in 300 mL dioxane was added dropwise, 26.6 g (0.2 mol) chloroanhydride of methylphosphonic acid in 100 mL dioxane, keeping the temperature below 5 C The reaction mixture was stirred at room temperature overnight The reaction product was separated from the reaction mixture by filtration The resulting solution was subjected to vacuum distillation (yield 14.35 g, 30%) General procedure of the melt polycondensation [H W Coover, R F McConnell, M A McCall, Ind Eng Chem., 52, 409 (1960)] In general, the acid chloride condensations were effected under anhydrous conditions by mixing phosphorus acid chloride, dihydroxy aromatic compound, and anhydrous magnesium chloride (0.1À0.2 g when 0.1 mol of each reactant was Poly[alkylene(arylene) alkyl or arylphosphonate]s 317 used) in an atmosphere of dry nitrogen, then heating the mixture to 90 C, the lowest temperature at which the reactants dissolved and hydrogen chloride was evolved rapidly Reaction mixtures containing p,p0 -biphenol or 4,40 -sulfonyldiphenol, however, had to be heated initially to 130À160 C to obtain a melt The reaction mixture was swept with nitrogen for the first hour to remove the evolved hydrogen chloride and to provide an inert atmosphere Then the reaction mixture was stirred, and a vacuum was applied gradually to remove the evolved hydrogen chloride The vacuum could not be used in the initial stages because some of the acid chloride distilled out and the dihydroxy compound sublimed on the upper surface of the reaction flask In some cases, the temperature was raised gradually to the desired maximum temperature; in others, a heating schedule of h each of 90 C, 120 C, 150 C, and 200 C was followed The pressure was reduced to 1À5 mm during the last h of the reaction to ensure a satisfactory increase in molecular weight The flask and contents were cooled to 25 C before air was admitted General procedure of the interfacial polycondensation [F Millich, C E Carraher Jr., J Polym Sci Part A-1, 7, 2669 (1969)] Hydroquinone (HQ, 2.32 g, 0.021 mol) was added to the reaction jar before capping and connecting the tubes Only for Ba(OH)2 (granular solid) was the base introduced with HQ The system was flushed with Nz for before the aqueous medium (deaerated by boiling, 100 mL) was introduced After the jar contents were stirred for min, CCI (100 mL), containing PPD (4.10 g, 0.021 mol), was run in quickly After 30 s, more than sufficient 1N aqueous HCl was added to reduce the pH to below (about 1.2 times the theoretical amount of HCl needed to neutralize the original amount of base) Polymer separates from the solution as a tacky, coherent mass, adhering to the container surface Most often, the liquid phases could be separated by decantation without the need for filtration (Rarely was residue found dissolved.) Acetone (75 mL) was added to the blender and stirred for min, producing a solution, designated as the original acetone-soluble portion (OAS), and a granular solid, designated as original acetone-insoluble (OAI), which was easily poured on a suction filter and separated An aliquot of the acetone solution was evaporated on a steam bath, yielding a clear film, and was weighed for estimation of the total yield of OAS fraction The solid was washed with 50 mL portions of water and acetone, and dried and weighed (OAI) Alternatively, all of the original polymer may be dissolved in tert-butyl alcohol because the higher molecular weight material (OAI) is effectively solubilized by the OAS fraction General procedure of the low temperature solution polycondensation [D J Liaw, W C Shen, Polymer, 34, 1336 (1993)] A flask equipped with a paddle stirrer, additional funnel, and reflux condenser was charged with 5.0 g (20 mmol) of 4,40 -sulphonyldiphenol, 60 mL of methylene chloride, and 4.44 g (44 mmol) of triethylamine, and subjected to vigorous stirring at 0 C Then the solution of 4.1 g (20 mmol) of phenyl phosphonic dichloride and 10 mL of methylene chloride was slowly added to the flask (B1 h) During the addition, an exothermic reaction occurred After the whole quantity was added, the reaction mixture was allowed to warm to room temperature and was subsequently refluxed for h The polymer solution was washed with dilute HCl (1%) and 318 Polyphosphoesters distilled water until the aqueous phase was neutral to litmus paper The solution was filtered and the polymer precipitated with methanol The white polymer was dried in vacuo at 60 C for 24 h General procedure of the liquidÀvapor interfacial polycondensation [S Iliescu, G Ilia, A Popa, G Dehelean, L Macarie, L Pacureanu, N Hurduc, Polymer Bull., 46, 165 (2001)] For the liquidÀvapor interfacial polycondensation, a round-bottom flask is used, immersed in an oil bath; the appropriate phosphorus dichloride was heated and carried, by a stream of nitrogen, in the flask 2, containing aqueous NaOH and bisphenol A The nitrogen stream acts as carrier gas for the phosphorus dichlorides, as reaction mixture protector from the atmospheric oxygen, and for agitation of the reaction mixtures The reaction rate can be controlled by the nitrogen flow rate The entire quantity of phosphonic dichloride is transported with nitrogen from the round-bottom flask to For the separation of the formed polymer, the reaction mixture from flask was filtered on G4 glass funnel, under vacuum To prevent the possibility of condensation of the reagent vapor on apparatus walls, the vapor mixture is overheated so that the partial pressure of the vapor reagent in the gas mixture is lower than its saturation vapor pressure Polymer separates from solution as a tacky, coherent mass, adhering to the container surface The solid polymer was washed with distilled water until free of chloride ion and dried at 50 C, in vacuum The yield in polymer was 85% Inherent viscosity of the polymer in dichloroethane was 0.95 dL/g, measured at a concentration of 0.5 g/dL, at 30 C General procedure of IPTC polycondensation [S Iliescu, A Pascariu, N Plesu, A Popa, L Macarie, G Ilia, Polymer Bull., 63, 485 (2009)] The polymers were synthesized according to the following procedure: 0.005 mol diol dissolved in 20 mL aqueous solution NaOH (0.8 g) was added to a stirred solution of 0.005 mol phenylphosphonic (phosphoric) dichlorides, 0.0025 mol catalyst in 10 mL CH2Cl2, keeping the temperature below 15 C; then the mixture was stirred (1000 rpm) for 90 at 15 C The polycondensation can be carried out at pH 9À10, to minimize hydrolysis side reactions The supernatant aqueous layer was decanted, and the organic layer was washed successively with water to neutral pH and to remove any residual impurities The organic mixture was precipitated by pouring the solution into excess hexane The polymer was collected and dried under vacuum at 50 C until constant weight and then characterized General procedure for synthesis of poly(phenyl phosphonate) from bisphenol A diglycidyl ether (BPGE) with phenylphosphonic dichloride (PPDC) [T Nishikubo, A Kameyama, S Minegishi, Macromolecules, 28, 4810 (1995)] A typical procedure for polyaddition of BPGE with PPDC was as follows: BPGE (0.6809 g, mmol), PPDC (0.3900 g, mmol), and TBAC (27.8 mg, 0.1 mmol) were dissolved in toluene (2 mL), and then the reaction was carried out at 90 C for 24 h The reaction mixture was diluted by the addition of chloroform (10 mL) and washed with water (2 mL), and then some amount of chloroform was evaporated The concentrated polymer solution was poured into hexane (100 mL), reprecipitated twice from chloroform into hexane, and dried in vacuo at 60 C The Poly[alkylene(arylene) alkyl or arylphosphonate]s 319 yield of polymer was 1.018 g (95%) The average molecular weight (Mn) of the polymer determined from GPC was 1.63 l04 IR (film): 1250 (CaOaC), 1180 (PQO), 990 (PaOaC, 750 (CaC1) cm21 1H NMR (90 MHz, CDC13, TMS) 1.60 (s, 6H, CH3), 3.59À4.00 (m, 4H, CH2C1), 4.00À4.50 (m, 4H, CH2aO), 4.70À5.18 (m, 2H, CHaO, 6.90À8.10 (m, 13H, aromatic protons) General procedure for synthesis of poly(methyl phosphonate) from bisphenol A diglycidyl ether (BPGE) with methylphosphonic dichloride (MPDC) [T Nishikubo, A Kameyama, S Minegishi, Macromolecules, 28, 4810 (1995)] BPGE (0.6809 g, mmol) was made to react with MPDC (0.2658 g, mmol) in the presence of TBAC (27.8 mg, 0.1 mmol) in toluene (2 mL) at 90 C for 24 h The reaction mixture was diluted with chloroform and washed with water, and some amount of chloroform was evaporated The polymer solution was poured into hexane, reprecipitated twice from chloroform into hexane, dried in vacuo at 60 C The yield of polymer was 0.596 g (63%) Mn of the polymer determined from GPC was 2.31 l04 IR (film): 1244 (CaOaC), 1182 (PQO), 981 (PaOaC), 731 (CaC1) cm2 l 1H NMR (90 MHz, CDC13, TMS): 1.61 (s, 6H, CH3), 1.63 (dt, J 2.20 Hz and 18.02 Hz, 3H, PaCH3), 3.49À4.05 (m, 4H, CH2Cl), 4.05À4.30 (m, 4H, CH2aO), 4.70À5.20 (m, 2H, CHaO), 6.95À7.21 (m, 8H, aromatic protons) Synthesis of BHDBÀpoly(arylate-co-phosphonate) [T Ranganathan, B.-C Ku, J Zilberman, M Beaulieu, R J Farris, E B Coughlin, T Emrick, J Polym Sci Part A: Polym Chem., 45, 4573 (2007)] In a dry round-bottom flask equipped with an addition funnel and mechanical stirrer was added a solution of BHDB (1.0 g, 4.4 mmol) in anhydrous dichloromethane (16 mL) and anhydrous triethylamine (1.5 mL, 1.1 g, 11 mmol) To this was added DMAP (15 mg, 0.01 mmol), and the flask was cooled to 25 C, using an ice/ethanol bath A solution of PPDC (0.60 mL, 2.2 mmol) and isophthaloyl chloride (0.45 g, 2.2 mmol) in anhydrous dichloromethane (10 mL) was added dropwise by addition funnel to the vigorously stirring reaction mixture over The reaction mixture was then allowed to warm to room temperature and stirred there for h Phenol (45 mg, 0.5 mmol) was added, and stirring was continued for h Then, the reaction mixture was diluted with dichloromethane (250 mL), washed with cold water (5 40 mL), dried over anhydrous magnesium sulfate, concentrated to a volume of about 20 mL, and precipitated into a stirred solution of cold acetone (B500 mL) to get a white fibrous solid The solid was filtered, washed with acetone, and dried in a vacuum oven at 60 C to give 1.45 g of a white solid (yield 95%) FTIR (powder, cm21): 1738 (CQO (O)), 1683 (CQO), 1443 (PaC), 1272 (PQO), 1200 (PaOaC) 31 P{H} NMR (121 MHz, DMSO-d6, ppm): δ 12.64 (s), 12.70 (s), 12.74 (s) 1H NMR (400 MHz, DMSO-d6, ppm): δ 4.33, 4.42, 4.50 (s, 2H), 7.1À7.38 (m, 6H), 7.56 (m, 2H), 7.72 (m, 1H), 7.95 (m, 4H), 8.45 (m, 2H), 8.8 (m, 1H) 13C{H} NMR (100 MHz, DMSO-d6, ppm): δ 43.7, 43.8, 43.9, 120.2, 121.3, 122.4, 123.1, 127.8, 128.2, 128.5, 130.9, 131.5, 132.9, 133.2, 134.9, 136.2, 148.3, 149.9, 154.3, 154.9, 163.4, 164.5, 196.2, 196.3, 196.4 ppm Synthesis of BPAÀpoly(arylate-co-phosphonate) 320 Polyphosphoesters [T Ranganathan, B.-C Ku, J Zilberman, M Beaulieu, R J Farris, E B Coughlin, T Emrick, J Polym Sci Part A: Polym Chem., 45, 4573 (2007)] Polymer was prepared as described for 1, using BPA (1.0 g, 4.4 mmol), triethylamine (1.5 mL, 11 mmol), DMAP (15 mg, 0.01 mmol), PPDC (0.60 mL, 2.2 mmol), and isophthaloyl chloride (0.45 g, 2.2 mmol) in anhydrous dichloromethane (25 mL) The dichloromethane solution of the polymer, after washing with water, was precipitated into a stirred solution of cold hexane to afford 1.4 g of a white fibrous solid (yield 92%) FTIR (powder, cm21): 1739 (C(O)aO), (PaC), 1297 (PQO), 1194 (PaOaC) 31 P{H} NMR (162 MHz, CDCl3, ppm): δ 12.5 (s) 1H NMR (400 MHz, CDCl3, ppm): δ 1.58, 1.66, 1.74 (s, 6H), 7.09 (m, 6H), 7.16 (m, 5H), 7.25 (m, 3H), 7.34 (m, 2H), 7.50 (m 2H), 7.59 (m, 1H), 7.67 (m, 1H), 7.96 (m, 2H), 8.45 (m, 2H), 9.0 (m, 1H) 13C{H} NMR (100 MHz, CDCl3, ppm): 30.9, 30.95, 31.0, 42.3, 42.5, 42.6, 120.0, 121.0, 127.9, 128.1, 128.6, 128.7, 130.4, 132.3, 133.2, 134.9, 147.1, 148.2, 148.6, 148.7, 164.3 Poly[alkylene(arylene) phosphite]s and Poly[alkylene(arylene) phosphonite]s Poly[alkylene(arylene) phosphite]s and poly[alkylene(arylene) phosphonite]s are P O X O OR P n O X O R n polyesters of phosphorus (I) and phosphonous (II) acids, respectively In these polyesters, the phosphorus atom is trivalent HO P OH OH I HO P OH R II The most important feature of the polyphosphoesters of the trivalent phosphorus atom is their high reactivity, predetermined by the oxidation state of the phosphorus atom (13) The most characteristic reactions for these polyphosphoesters are oxidation, addition of sulfur, and Arbuzov alkylation The polyphosphites and polyphosphonites are viscous liquids or glass-like substances, depending on the composition, and adhere to glass, metal, and wood METHODS FOR PREPARATION Poly[alkylene(arylene) phosphite]s and poly[alkylene(arylene) phosphonite]s are prepared mainly by: (1) polycondensation of diamides and diesters of the corresponding trivalent phosphorus acids with dihydroxy aliphatic or aromatic compounds, (2) polytransesterification of esters of phosphorus and phosphonous acids with dihydroxy aromatic or aliphatic compounds, and (3) ring-opening polymerization of cyclic phosphite esters Polyphosphoesters DOI: 10.1016/B978-0-12-416036-1.00004-8 © 2012 Elsevier Inc All rights reserved 322 Polyphosphoesters 1.1 Polycondensation of Diamides of the Phosphorus and Phosphonous Acids with Dihydroxy Aliphatic or Aromatic Compounds Linear polyphosphites and polyphosphonites are synthesized by polycondensation of diamides of the corresponding trivalent phosphorus acids with glycols (see Appendix) [1] C2H5 C2H5 N nC2H5 P + nHO N OR (R) R' OH C2H5 P –(2n–1)N]HN(C2H5)2 R' O O n OR (R) – ROH P O R' O x OR P O R' O O R' O P y OR The glycols used were 1,5-pentane diol, 1,6-hexane diol, 1,4-butene-2 diol, p-di (hydroxymethyl)benzene, and sorbitol It was found that this reaction takes place vigorously in the majority of cases and is accompanied by the evolution of diethylamine, which is removed by vacuum Under reaction conditions (100 C), 1,5-pentane diol and 1,6-hexane diol form both linear polymer and cyclic phosphites and phosphonites The diamides of monoalkyl phosphorus acid form linear polyphosphites containing branched unites The formation of such polymer is due to the participation of the alkoxy group in transesterification reaction with diols at the reaction conditions The formation of branched polymer is confirmed by the fact that polyphosphites, in contrast to polyphosphonites, are insoluble in organic solvents and possess rubber-like properties The polyphosphites and polyphosphonites are viscous liquids or glass-like substances, possessing adhesion to glass, metal, and wood The molecular weights determined by the light scattering method reached values from 50,000 to 200,000 Da These polymers are reactive substances They tend to undergo thermal disproportionation (ester exchanged), which is frequently associated with processes of polymerization and depolymerization Thus, on heating to 220 C in vacuum, poly (pentamethylene methylphosphonite) depolymerizes to cyclic pentamethylene methylphosphonite, which distills out from the reaction vessel completely On storage, the monomer rapidly polymerizes (molecular weight 2000À3000 Da) O O (CH2)5 O P CH3 n 220°C P (H2C)5 O CH3 r.t O (CH2)5 O P CH3 m Polymers derived from p-di(hydroxymethyl) benzene are not converted into monomer on heating Poly[alkylene(arylene) phosphite]s and Poly[alkylene(arylene) phosphonite]s 323 1.1.1 Reactivity of Polyphosphites and Polyphosphonites Polyphosphites and polyphosphonites are comparatively easily oxidized Oxidation with nitric oxide resulted in the formation of the corresponding polyphosphate or poly(alkylphosphonate) (see Appendix) O P O R' NO O OR (R) P O R' O OR (R) n n The addition of sulfur to polyphosphites and polyphosphonites occurs at 110 C to provide the corresponding poly(alkylene thiophosphate) and poly(alkylalkylene thiophosphonate) (see Appendix) S P O R' S O OR (R) P O R' O OR (R) n n Any excess of sulfur can be removed from the reaction product by washing with ether or methanol Polyphosphites can be converted into poly(alkylalkylene phosphonate)s by Arbuzov alkylation When the alkylation is carried out with dihalogenoalkane, cross-linked product is formed O P R′′X P O R' O R' O R′′ n O XR′′X OR n Cross-linked polymer When polyphosphites are treated with a small amount of S2Cl2 (sulfur monochloride) (the reaction takes place with some spontaneous evolution of heat), a cross-linked product with rubber-like properties is formed O P OR O R' + S2Cl2 O n P O R' O –RCl –RCl S2Cl n Cross-linked polymer 324 Polyphosphoesters Thus, the polyphosphoesters of trivalent phosphorus acids obtained by polycondensation of diamides of monoalkylphosphites and alkylphosphonites with diols undergo a number of chemical transformations, resulting in the formation of linear and cross-linked polyphosphates, polythiophosphates, and poly(alkylphosphonate)s The reaction of tetraethyldiamides of phosphorus and phosphonous acids with hydroquinone was used for the preparation of the corresponding aromatic polyphosphonites and polyphosphites [2] C2H5 C2H5 N n C2H5 P R N nHO C2H5 OH P –(2n–1)HN(C2H5)2 O O R n R = CH3; C6H5; OC4H9; OC2H5; OC6H5 The polycondensation process lasts for 4À5 h, and the diethylamine is liberated in an amount close to the theoretical ideal The resulting polyphosphoesters are transparent, slightly yellowish, either solid products They possess good adhesion to glass and not burn on being removed from a flame The reaction of hydroquinone with diamides of phosphorus and phosphonous acids in the presence of a small amount (3À5%) of phosphorus triamide forms a partially cross-linked polyphosphoester On treatment with oxygen or sulfur, these polyesters can be quantitatively converted into the corresponding poly(alkylphosphonate)s, polyphosphates or polythiophosphonate, and polythiophosphates 1.2 Polytransesterification of Diesters of Phosphorus and Phosphonous Acids with Dihydroxy Aromatic or Aliphatic Compounds The phenyl esters of phosphonous and phosphorus acids are available compounds Triphenyl and diphenyl phosphites were prepared by the methods described in Ref [3] (Ref [38], Chapter 1) The diphenyl esters of methyl and phenylphosphonous acids were prepared in 90% yield by heating the corresponding acid dichloride with phenol without solvent or hydrogen chloride acceptor (see Appendix) RPCl2 + 2C6H5OH R P(OC6H5)2 –2HCl R = CH3; C6H5 Ayres and Rydon [4] (Ref [2], Chapter 3) were the first to announce that polytransesterification of triphenyl phosphite with 1,6-hexane diol created polyphosphites (PhO)3P + HO(CH2)6OH P O OPh (CH2)6 O n Poly[alkylene(arylene) phosphite]s and Poly[alkylene(arylene) phosphonite]s 325 They did not give any information about the properties of this polymer They accepted that the monotransesterified product obtained at the first stage of the reaction undergoes further transesterification to eventually form polymer Poly(arylene phosphite)s and poly(arylene phosphonite)s are synthesized by transesterification of diphenyl phosphite, diphenyl methylphosphonite, diphenyl phenylphosphonite, or triphenyl phosphite with aromatic di- and trihydroxy compounds [5] nRP(OC6H5)2 + nHO Ar OH –(2n–1)C6H5OH P O Ar R ; n CH3 R = CH3; C6H5; OC6H5; OH Ar = O ; C CH3 Polytransesterification proceeds smoothly with liberation of approximately the theoretical quantity of phenol The polyphosphites and polyphosphonites are obtained in almost theoretical yield Reaction of the diesters of phosphorus and phosphonous acids with dihydroxy aromatic compounds produces linear polyphosphates and polyphosphoesters, whereas the reaction with trihydroxy aromatic compounds or triphenyl phosphite yielded cross-linked or branched polymers The linear polymers are solid, transparent, glassy substances They can easily be drawn into fibers from the melt The average molecular weight of a linear polyphosphoesters is from 40,000 to 100,000 Da 1.3 Ring-Opening Polymerization of Cyclic Esters of Phosphorus and Phosphonous Acids Polyphosphites and polyphosphonites are synthesized using the same procedure of diamides of the corresponding trivalent phosphorus acids with methyl glucoside (Scheme 4.1) [6] This method is chosen for the preparation of the polyphosphite and polyphosphonite based on the monosaccharides because the latter is an acidophobic, thermally unstable substance, and this method did not require high reaction temperatures Good results were obtained only when the synthesis was carried out in two stages: first a phosphorylation stage, i.e., the formation of mainly lowmolecular-weight cyclic phosphites (phosphonites) and second a completion stage, the ring-opening polymerization (Scheme 4.1) The main reason for this direction of the reaction is the conformational peculiarity of the methyl glucoside molecule The equatorial substituents in positions and of the pyranose ring create favorable steric conditions for the closing of readily formed and stable six-membered phosphonite It was shown that when methyl glucoside reacts with methylphosphonous tetraethyldiamide in the presence of solvent or without one, polymers with 326 Polyphosphoesters O CH2OH + CH3 P[N(C2H5)2]2 OH O O O –2NH(C2H5)2 P CH3 Second stage OCH2 O P OR(R) O n Scheme 4.1 Ring-opening polymerization of cyclic esters of phosphorus acid molecular weights (determined by the light scattering method) of 321,000 and 528,000 Da are obtained, respectively Once the polyphosphite and polyphosphonite are obtained, they can be converted by oxidation with nitric oxide or addition of sulfur into the corresponding cyclic esters of polyphosphate, polythiophosphate, poly(alkylphosphonate), and poly(alkyl thiophosphonate) Analogous results were obtained from the reaction of the polytransesterification of the dimethyl and diethyl esters of phenylphosphonous acid with certain glycols, leading to the formation of poly(alkyleneglycol phosphonite)s [7] To study the intermediate products formed in the process of polytransesterification of methyl ester of phenylphosphonous acid with diethyleneglycol, the reaction mixture was vacuum distilled after h heating at 140 C Cyclic ester of phenylphosphonous acid in 70% yield was isolated at 125À132 C/3 mmHg When polytransesterification was conducted under more vigorous conditions (at 170 C and 10 h), no cyclic ester was found in the reaction mixture These results show that the polytransesterification of dialkyl phenyl- and ethylphosphonites with glycols of the aliphatic series occurs mainly or entirely via cyclic phosphonite O nC6H5P(OR')2 + nHO R OH –2R'OH C6H5 P R O R = CH2CH2; CH2CH2OCH2CH2 O R O P C6H5 n Poly[alkylene(arylene) phosphite]s and Poly[alkylene(arylene) phosphonite]s 327 The results from the kinetic studies of the reaction of dimethyl ester of phenylphosphonous acid with diethyleneglycol revealed that it is a second-order reaction It was found that the reactivity of the glycols fell in the following order: Ethyleneglycol diethyleneglycol tetraethyleneglycol References K A Petrov, E Ye Nifant’ev, R G Goltsova, L M Solntseva, Vysokomol Soyed., 5, 1961 (1963) K A Petrov, V P Yevdakov, K A Bilevich, Yu S Kosyrev, V P Radchenko, Vysokomol Soyed., 6, 10 (1964) K A Petrov, E Ye Nifant’ev, R G Goltsova, A A Shchegolev, B V Bushmin, Zh Obshch Khim., 32, 3723 (1962) D C Ayres, H N Rydon, J Chem Soc., 1109 (1957) K A Petrov, E Ye Nifant’ev, L V Khorkhoyanu, R G Goltsova, Vysokomol Soyed., 5, 1799 (1963) K A Petrov, E Ye Nifant’ev, T N Lysenko, A I Suzanski, Vysokomol Soyed., 5, 712 (1963) A N Pudovik, G I Yevstafyev, Vysokomol Soyed., 6, 2139 (1964) Appendix General procedure for preparation of polyphosphonites [K A Petrov, E Ye Nifant’ev, R G Goltsova, L M Solntseva, Vysokomol Soyed., 5, 1961 (1963)] A flask was charged with mol of glycol and mol of methylphosphonous tetraethyldiamide The reaction mixture was heated in the presence of inert gas to 100 C for 4À6 h After that, the reaction mixture was subjected to vacuum (10 mmHg) for 30 at 100 C The polymer is obtained in quantitative yield When 1,6-hexsane diol is used as glycol, the reaction proceeds at 180 C for h The molecular weight of the resulting poly(methyl hexamethylene phosphonite) is 200,000 Da General procedure for preparation of polyphosphites [K A Petrov, E Ye Nifant’ev, R G Goltsova, L M Solntseva, Vysokomol Soyed., 5, 1961 (1963)] A flask was charged with mol of glycol and mol of butyl tetraethylphosphordiamide The reaction mixture was heated in the presence of inert gas to 110À120 C The reaction is completed at 140À160 C for h The reaction product is a rubber-like substance insoluble in water and organic solvents 328 Polyphosphoesters General procedure for oxidation of polyphosphites and polyphosphonites [K A Petrov, E Ye Nifant’ev, R G Goltsova, L M Solntseva, Vysokomol Soyed., 5, 1961 (1963)] A flask protected from atmospheric moisture was charged with 15 g (0.09 mol) poly(hexamethylene methylphosphonite) solution in dimethylformamide, and NO (nitric oxide) was bubbled in it at 100 C for 4À5 h After completion of the reaction, the reaction mixture was kept for 15À20 in vacuum (10 mmHg) at 100 C The yield of poly(hexamethylene methylphosphonate) was 16.4 g, 97.7% General procedure for addition of sulfur to polyphosphites and polyphosphonites [K A Petrov, E Ye Nifant’ev, T, N Lysenko, A I Suzanski, Vysokomol Soyed., 5, 712 (1963)] A solution of 2.5 g of polyphosphite in 10 mL dimethylformamide was treated with 0.24 g of sulfur, and the reaction mixture was heated for h at 130 C The corresponding polythiophosphonate was obtained in quantitative yield, with softening point at 75 C General procedure for preparation of diphenyl methylphosphonite [K A Petrov, E Ye Nifant’ev, L V Khorkhoyanu, R G Goltsova, Vysokomol Soyed., 5, 1799 (1963)] 50.7 g of phenol was placed in a distillation apparatus, and 30 g of methyldichlorophosphine was added dropwise at 50À60 C A current of inert gas was passed through the reaction mixture, which was then heated at 100 C For the final stage, the reaction mixture was heated in vacuum at 100 C and 100 mmHg for 30 Diphenyl methylphosphonite was obtained in 90% yield (53.9 g) Using the method described above diphenyl phenylphosphite was obtained in 90% yield (44 g) reacting 30 g phenyldichlorophosphine and 35 g phenol ... Polymer Chemistry; European Journal of Medicinal Chemistry; Amino Acids; and Tetrahedron Letters In October 2006, Elsevier published his book Chemistry and Application of H-phosphonates Since 2003,... Bioorganic & Medicinal Chemistry; Journal of Medicinal Chemistry; Macromolecular Rapid Communication; Polymer Degradation and Stability; Journal of Polymer Science, Part A: Polymer Chemistry; European.. .Polyphosphoesters Chemistry and Application Kolio Dimov Troev Institute of Polymers Bulgarian Academy of Sciences