Diels-Alder Click Reaction Research Articles

Various polycarbonate graft copolymers via diels–alder click reaction

AbstractIn this work, we used Diels–Alder click reaction for the preparation of various types of aliphatic polycarbonates (PCs). We first prepared a novel anthracene‐functionalized cyclic carbonate monomer, anthracen‐9‐ylmethyl 5‐methyl‐2‐oxo‐1,3‐dioxane‐5‐carboxylate (2), followed by ring‐opening polymerization of this monomer to prepare PC with pendant anthracene groups (PC‐anthracene) using 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU)/1‐(3,5‐bis(trifloromethyl)phenyl)‐3‐cyclohexylthiourea (TU) as the catalyst and benzyl alcohol as the initiator in CH2Cl2 at room temperature. Subsequently, the resulting PC‐anthracene (Mn,TDGPC = 6000 g/mol, Mw/Mn = 1.22) was grafted with a linear α‐furan protected‐maleimide terminated‐poly(methyl methacrylate) (PMMA‐MI) (Mn,GPC = 3100 g/mol, Mw/Mn = 1.31), or poly(ethylene glycol) (PEG‐MI) (Mn,GPC = 550 g/mol, Mw/Mn = 1.09), or a mixture of PMMA‐MI and PEG‐MI to yield well‐defined PC graft or hetero graft copolymers, PC‐g‐PMMA (Mn,TDGPC = 59000 g/mol, Mw/Mn = 1.22) or PC‐g‐PEG, or PC‐g‐(PMMA)‐co‐PC‐g‐(PEG) (Mn,TDGPC = 39900 g/mol, Mw/Mn = 1.16), respectively, using Diels–Alder click reaction in toluene at 110°C. The Diels–Alder grafting efficiencies were found to be over 97% using UV spectroscopy. Moreover, the structural analyses and the molecular weights of resulting graft copolymers were determined via 1H NMR and triple detection GPC (TD‐GPC), respectively. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Synthesis of tadpole polymers via triple click reactions: Copper-catalyzed azide-alkyne cycloaddition, diels-alder, and nitroxide radical coupling reactions

We designed a trifunctional initiator (3) containing anthracene, bromide, and OH functionalities and subsequently used as an initiator in atom transfer radical Polymerization (ATRP) of styrene to yield linear polystyrene (PS) with α-anthracene, OH, and ω-bromide terminal groups, of which bromide is later transformed into azide to result in the linear anthracene-, OH-, and azide-terminated PS (l-α-anthracene-OH-ω-azide-PS). The copper-catalyzed azide–alkyne cycloaddition reaction between l-α-anthracene-OH-ω-azide-PS and α-furan-protected-maleimide-ω-alkyne linkage, 4 afforded the linear anthracene-, OH-, and maleimide-terminated PS. The cyclization via intramolecular Diels–Alder click reaction of this linear PS and the subsequent conversion of the hydroxyl into bromide resulted in the cyclic PS with one bromide located on the ring, (c-PS)-Br. Finally, the c-PS-Br was clicked with either well-defined tetramethylpiperidine-1-oxyl-terminated poly(ethylene glycol) (PEG) or poly(ε-caprolactone) (PCL) yielding the tadpole polymer, (c-PS)-b-PEG or (c-PS)-b-PCL. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

3‐miktoarm star terpolymers using triple click reactions: Diels–Alder, copper‐catalyzed azide‐alkyne cycloaddition, and nitroxide radical coupling reactions

AbstractWell‐defined linear furan‐protected maleimide‐terminated poly(ethylene glycol) (PEG‐MI), tetramethylpiperidine‐1‐oxyl‐terminated poly(ε‐caprolactone) (PCL‐TEMPO), and azide‐terminated polystyrene (PS‐N3) or ‐poly(N‐butyl oxanorbornene imide) (PONB‐N3) were ligated to an orthogonally functionalized core (1) in a two‐step reaction mode through triple click reactions. In a first step, Diels–Alder click reaction of PEG‐MI with 1 was performed in toluene at 110 °C for 24 h to afford α‐alkyne‐α‐bromide‐terminated PEG (PEG‐alkyne/Br). As a second step, this precursor was subsequently ligated with the PCL‐TEMPO and PS‐N3 or PONB‐N3 in N,N‐dimethylformamide at room temperature for 12 h catalyzed by Cu(0)/Cu(I) through copper‐catalyzed azide‐alkyne cycloaddition and nitroxide radical coupling click reactions, yield resulting ABC miktoarm star polymers in a one‐pot mode. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Linear tetrablock quaterpolymers via triple click reactions, azide‐alkyne, diels–alder, and nitroxide radical coupling in a one‐pot fashion

AbstractAzide‐alkyne and Diels–Alder click reactions together with a click‐like nitroxide radical coupling reaction were used in a one‐pot fashion to generate tetrablock quaterpolymer. The various living polymerization generated linear polymers with orthogonal end‐functionalities, maleimide‐terminated poly(ethylene glycol) (PEG‐MI), anthracene‐ and azide‐terminated polystyrene, alkyne‐ and bromide‐terminated poly(tert‐butyl acrylate) or alkyne‐poly(n‐butyl acrylate), and tetramethylpiperidine‐1‐oxyl (TEMPO)‐terminated poly(ε‐caprolactone) (PCL‐TEMPO) were clicked together in a one‐pot fashion to generate PEG‐b‐PS‐b‐PtBA‐b‐PCL or PEG‐b‐PS‐b‐PnBA‐b‐PCL quaterpolymer using Cu(0), CuBr, and N,N,N′,N″,N″‐pentamethyldiethylenetriamine as catalyst in dimethyl formamide at 80 °C for 36 h. Linear precursors and target quaterpolymers were analyzed via 1H NMR and gel permeation chromatography. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Diels−Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering

Hyaluronic acid (HA) is a naturally occurring polymer that holds considerable promise for tissue engineering applications. Current cross-linking chemistries often require a coupling agent, catalyst, or photoinitiator, which may be cytotoxic, or involve a multistep synthesis of functionalized-HA, increasing the complexity of the system. With the goal of designing a simpler one-step, aqueous-based cross-linking system, we synthesized HA hydrogels via Diels-Alder "click" chemistry. Furan-modified HA derivatives were synthesized and cross-linked via dimaleimide poly(ethylene glycol). By controlling the furan to maleimide molar ratio, both the mechanical and degradation properties of the resulting Diels-Alder cross-linked hydrogels can be tuned. Rheological and degradation studies demonstrate that the Diels-Alder click reaction is a suitable cross-linking method for HA. These HA cross-linked hydrogels were shown to be cytocompatible and may represent a promising material for soft tissue engineering.

Sequential double polymer click reactions for the preparation of regular graft copolymers

AbstractIn this study, graft copolymers with regular graft points containing polystyrene (PS) backbone and poly(methyl methacrylate) (PMMA), poly(tert‐butyl acrylate) (PtBA), or poly (ethylene glycol) (PEG) side chains were simply achieved by a sequential double polymer click reactions. The linear α‐alkyne‐ω‐azide PS with an anthracene pendant unit per chain was produced via atom transfer radical polymerization of styrene initiated by anthracen‐9‐ylmethyl 2‐((2‐bromo‐2‐methylpropanoyloxy)methyl)‐2‐methyl‐3‐oxo‐3‐(prop‐2‐ynyloxy) propyl succinate. Subsequently, the azide–alkyne click coupling of this PS to create the linear multiblock PS chain with pendant anthracene sites per PS block, followed by Diels–Alder click reaction with maleimide end‐functionalized PMMA, PtBA, or PEG yielded final PS‐g‐PMMA, PS‐g‐PtBA or PS‐g‐PEG copolymers with regular grafts, respectively. Well‐defined polymers were characterized by 1H NMR, gel permeation chromatography (GPC) and triple detection GPC. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Catalytic synthesis and post-polymerization functionalization of conjugated polyisoprene

Anionically synthesized polyisoprene (PI) was catalytically isomerized with RuHCl(CO)(PPh3)3 to produce conjugated PI (CPI). Both the reaction time and temperature were varied to control the number of conjugated dienes along the CPI backbone. The same reaction scheme also conjugated polycyclooctadiene, demonstrating the utility of the catalyst to conjugate other olefin-containing polymers. The CPI samples retained their narrow distributions as indicated by size exclusion chromatography (SEC). Small molecules were coupled with CPI through the Diels–Alder click reaction in solution to produce an array of post-polymerization functionalized polymers. In one example, N-2-hydroxyethyl maleimide (HEMI) was coupled to CPI to produce a hydroxylated material. L-Lactide was polymerized from this macroinitiator with both tin(II) octoate (Sn(Oct)2) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) to produce poly(L-lactide) (PLLA) grafted from PI (PI-g-PLLA) with a monomodal SEC distribution at 95 wt% PLLA content.

Synthesis of ABC type miktoarm star copolymers by triple click chemistry

An ABC type miktoarm star copolymer possessing polystyrene (PS), poly(e-caprolactone) (PCL) and poly(ethylene glycol) (PEG) arms was synthesized by combining existing triple click chemistries, namely thiol–ene, copper catalyzed azide–alkyne cycloaddition (CuAAC) and Diels–Alder (DA) reactions. For this purpose, a core (1-(allyloxy)-3-azidopropan-2-yl (anthracen-9-ylmethyl) succinate) with allyl, azide and anthracene functionalities was synthesized in two steps with high yields. Then, polymers with corresponding clickable sites, namely ω-thiol polystyrene (PS-SH), α-alkyne poly(e-caprolactone) (alkyne-PCL) and ω-maleimide poly(ethylene glycol) (Me-PEG-MI), were independently prepared. As the first step of the grafting onto process, PS-SH was thiol–ene clicked onto the core to yield PS-N3-Ant. Finally, alkyne-PCL and Me-PEG-MI were bonded to PS-N3-Ant either in a sequential or a one-pot in situ manner using CuAAC and DA click reactions. All intermediates, related polymers at different stages and final PS-PCL-PEG miktoarm star copolymer were characterized by 1H NMR, FT-IR, and GPC analyses.

Graft copolymers via ROMP and Diels–Alder click reaction strategy

AbstractAnthracene‐functionalized oxanorbornene monomer and oxanorbornenyl polystyrene (PS) with ω‐anthracene end‐functionalized macromonomer were first polymerized via ring‐opening metathesis polymerization using the first‐generation Grubbs' catalyst in dichloromethane at room temperature and then clicked with maleimide end‐functionalized polymers, poly(ethylene glycol) (PEG)‐MI, poly(methyl methacrylate) (PMMA)‐MI, and poly(tert‐butyl acrylate) (PtBA)‐MI in a Diels–Alder reaction in toluene at 120 °C to create corresponding graft copolymers, poly(oxanorbornene)‐g‐PEG, poly(oxanorbornene)‐g‐PMMA, and graft block copolymers, poly(oxanorbornene)‐g‐(PS‐b‐PEG), poly(oxanorbornene)‐g‐(PS‐b‐PMMA), and poly(oxanorbornene)‐g‐(PS‐b‐PtBA), respectively. Diels–Alder click reaction efficiency for graft copolymerization was monitored by UV–vis spectroscopy. The dn/dc values of graft copolymers and graft block copolymers were experimentally obtained using a triple detection gel permeation chromatography and subsequently introduced to the software so as to give molecular weights, intrinsic viscosity ([η]) and hydrodynamic radius (Rh) values. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

Multiarm star polymers with peripheral dendritic PMMA arms through Diels-Alder click reaction

Dendritic 2- and 4-arm PMMA-based star polymers with furan-protected maleimide at their focal point, (PMMA)2n-MI and (PMMA)4n-MI were efficiently clicked with the peripheral anthracene functionalized multiarm star polymer, (α-anthryl functionalized-polystyrene)m-poly(divinyl benzene) ((α-anthryl-PS)m-polyDVB) through the Diels–Alder reaction resulting in corresponding multiarm star block copolymers: (PMMA)2n-(PS)m-polyDVB and (PMMA)4n-(PS)m-polyDVB, respectively. Molecular weights (Mw,TDGPC), hydrodynamic radius (Rh), and intrinsic viscosity (η) of the multiarm star polymers were determined using three-detection GPC (TD-GPC). The high efficiency of this methodology to obtain such sterically demanding macromolecular constructs was deduced using 1H-NMR and UV–vis spectroscopy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

Facile preparation of poly( N-isopropylacrylamide)-based hydrogels via aqueous Diels–Alder click reaction

The study reports a facile method of preparing poly( N-isopropylacrylamide)- based hydrogels by means of the Diels–Alder reaction. First, polymeric dienes were synthesized by free radical copolymerization between N-isopropylacrylamide (NIPA) and furfuryl methacrylate (FM), with 2, 2′-azobisisobutyronitrile (AIBN) as an initiator, and polymeric dienophile was obtained by a coupling reaction of poly(ethylene glycol) (PEG) and N-maleoyl- l-leucine (LMI) under N, N′-dicyclohexylcarbodiimide (DCC). Afterwards, the resultant dienes and dienophiles were dissolved in water and put in a refrigerator remaining a temperature of 9 °C, gelation via Diels–Alder reaction was observed after some time. The samples obtained at different steps were characterized by FTIR, NMR, GPC, SEM, CD, etc. It was found that LCST of copolymers decreases with the increase of FM content in copolymers. And the disassembly time of the hydrogels is closely related to the temperature and the solvents used. The swelling behavior study by gravimetric measurement indicates the hydrogels possess thermosensitivity and exhibit considerable swelling in water. Due to the simplicity of synthesis and no need for initiator or catalyzer and organic solvent, the strategy described here could find a promising application in the preparation of hydrogels.

Characterisation of N-vinyl-2-pyrrolidone-based hydrogels prepared by a Diels–Alder click reaction in water

N-vinyl-2-pyrrolidone-based hydrogels were prepared by the Diels–Alder reaction in water for the first time. Copolymers of N-vinyl-2-pyrrolidone(VP) and furfuryl methacrylate(FM) were synthesised by free radical polymerisation in toluene at 70 °C by using 2,2′-azobisisobutyronltrile as an initiator. Polymeric dienophile (PEG–AMI) was prepared from N-alaninyl maleimide (AMI) and poly(ethylene glycol) (PEG) by using N, N′-dicyclohexylcarbodiimide (DCC) as a dehydrating agent. The prepared dienes and dienophile were then dissolved in water and mixed, leading to gelation via Diels–Alder reaction after some time. The gelation times of different copolymers and PEG–AMI in different solvents and at different temperatures were measured by the vial inversion method, and the swelling behaviour of dried hydrogels was studied using a general gravimetric method. The gelation time was shorter in water than in organic solvents, and the gelation time decreased with the increase of temperature and FM content in copolymers. Conversely, the swelling ratios increased with the decrease of temperature and FM content in the copolymers. Disassembly experiments suggested that N, N-dimethylformamide (DMF) could accelerate the retro-DA reaction.

Ultra‐Fast RAFT‐HDA Click Conjugation: An Efficient Route to High Molecular Weight Block Copolymers

The use of the reversible addition fragmentation chain transfer-hetero Diels-Alder (RAFT-HDA) click reaction for the modular construction of block copolymers is extended to the generation of high molecular weight materials. Cyclopentadienyl end-functionalized polystyrene (PS-Cp) prepared via both atom transfer radical polymerization (ATRP) and the RAFT process are conjugated to poly(isobornyl acrylate) (PiBoA) (also prepared via RAFT polymerization) to achieve well-defined block copolymers with molecular weights ranging from 34 000 to over 100 000 g · mol(-1) and with small polydispersities (PDI < 1.2). The conjugation reactions proceeded in a very rapid fashion (less than 10 min in the majority of cases) under ambient conditions of temperature and atmosphere. The present study demonstrates-for the first time-that RAFT-HDA click chemistry can provide access to high molecular weight block copolymers in a simple and straight-forward fashion.

Synthesis of an ABCD 4-Miktoarm Star Quaterpolymer Through a Diels–Alder Click Reaction

An ABCD 4-miktoarm star quaterpolymer with A = poly(ε-caprolactone) (PCL), B = poly(tert-butyl acrylate) (PtBA), C = polystyrene (PS) and D = poly(methyl methacrylate) (PMMA) arms was prepared using the Diels–Alder reaction strategy. Firstly, PCL with anthracene (PCL-Anth) and PtBA with furan-protected maleimide (PtBA-MI) end-functionalities were synthesized separately via ring-opening polymerization of ε-CL and atom transfer radical polymerization of tBA, respectively. These homo-polymers were linked via the Diels–Alder click reaction in toluene at 100°C in order to give PCL-b-PtBA co-polymer. Next, this block co-polymer is utilized successively as macroinitiator in nitroxide-mediated radical polymerization of styrene and in free radical photo-polymerization of MMA in order to achieve the PCL-PtBA-PS-PMMA 4-miktoarm star quaterpolymer.

Multiarm star block copolymers via Diels‐Alder click reaction

AbstractTwo types of multiarm star block copolymers: (polystyrene)m‐poly(divinylbenzene)‐poly(methyl methacrylate)n, (PS)m‐polyDVB‐(PMMA)n and (polystyrene)m‐poly(divinylbenzene)‐poly(tert‐butyl acrylate)k, (PS)m‐polyDVB‐(PtBA)k were successfully prepared via a combination of cross‐linking and Diels–Alder click reactions based on “arm‐first” methodology. For this purpose, multiarm star polymer with anthracene functionality as reactive periphery groups was prepared by a cross‐linking reaction of divinyl benzene using α‐anthracene end functionalized polystyrene (PS‐Anth) as a macroinitiator. Thus, obtained multiarm star polymer was then reacted with furan protected maleimide‐end functionalized polymers: PMMA‐MI or PtBA‐MI at reflux temperature of toluene for 48 h resulting in the corresponding multiarm star block copolymers via Diels–Alder click reaction. The multiarm star and multiarm star block copolymers were characterized by using 1H NMR, SEC, Viscotek triple detection SEC (TD‐SEC) and UV. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 178–187, 2009

Preparation of 3‐arm star polymers (A3) via Diels–Alder click reaction

AbstractDiels–Alder click reaction was successfully applied for the preparation of 3‐arm star polymers (A3) using furan protected maleimide end‐functionalized polymers and trianthracene functional linking agent (2) at reflux temperature of toluene for 48 h. Well‐defined furan protected maleimide end‐functionalized polymers, poly (ethylene glycol), poly(methyl methacrylate), and poly(tert‐butyl acrylate) were obtained by esterification or atom transfer radical polymerization. Obtained star polymers were characterized via NMR and GPC (refractive index and triple detector detection). Splitting of GPC traces of the resulting polymer mixture notably displayed that Diels–Alder click reaction was a versatile and a reliable route for the preparation of A3 star polymer. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 302–313, 2008