Recent advances in the anionic synthesis of chain-end functionalized polymers

Recent results for the preparation of chain-end functionalized polymers using alkyllithium-initiated anionic polymerization are described. Termination with 4-chloro-1,1,1-trimethoxybutane has been used to prepare trimethoxy ortho ester (carboxyl)-functionalized polymers. Functionalization with the oxiranes, glycidoxypropyltrimethoxysilane, 3,4-epoxy-1-butene and 1,1,1-trifluoro-2,3-epoxypropane, has been investigated to prepare trimethoxysilyl-functionalized polymers, 1,3-diene-functionalized macro monomers and trifluoromethyl-functionalized polymers, respectively. Secondary amine-functionalized polymers have been prepared by termination with N-(benzylidene)methylamine and also using an N-benzyl tertiary amine-functionalized alkyllithium initiator followed by hydrogenolysis of the benzyl group.     

Tertiary amine-functionalized polymers by atom transfer radical polymerization

The quantitative synthesis of tertiary amine-functionalized polymers by atom transfer radical polymerization is reported. Tertiary amine-functionalized polystyrene was prepared with the adduct of 1-(bromoethyl)benzene with 1-(4-dimethyl-aminophenyl)-1-phenylethylene as an initiator in the atom transfer radical polymerization of styrene in the presence of a copper (I) bromide/2,2′-bipyridyl catalyst system. The polymerization proceeded via a controlled free-radical polymerization process to afford quantitative yields of the corresponding tertiary amine-functionalized polystyrene with predictable number-average molecular weights (1600–4400), narrow molecular weight distributions (1.09–1.31), and an initiator efficiency of 0.95. The polymerization process was monitored by gas chromatographic analysis. The tertiary amine-functionalized polymers were characterized by thin-layer chromatography, size exclusion chromatography, potentiometry, and spectroscopy. All experimental evidence was consistent with quantitative functionalization via the 1,1-diphenylethylene derivative. Polymerization kinetic measurements showed that the polymerization reaction followed first-order-rate kinetics with respect to monomer consumption and that the number-average molecular weight increased linearly with monomer conversion. © 2001 John Wiley & Sons, Inc. J Polym Sci A Part A: Polym Chem 39: 2058–2067, 2001     

A Synthetic Bioinspired Carbohydrate Polymer with Mucoadhesive Properties

Mucoadhesive polymers are of significant interest to the pharmaceutical, medical device, and cosmetic industries. Polysaccharides possessing charged functional groups, such as chitosan, are known for mucoadhesive properties but suffer from poor chemical definition and solubility, while the chemical synthesis of polysaccharides is challenging with few reported examples of synthetic carbohydrate polymers with engineered‐in ionic functionality. We report the design, synthesis, and evaluation of a synthetic, cationic, enantiopure carbohydrate polymer inspired by the structure of chitosan. These water‐soluble, cytocompatible polymers are prepared via an anionic ring‐opening polymerization of a bicyclic β‐lactam sugar monomer. The synthetic method provides control over the site of amine functionalization and the length of the polymer while providing narrow dispersities. These well‐defined polymers are mucoadhesive as documented in single‐molecule scale (AFM), bulk solution phase (FRAP), and ex vivo tissue experiments. Polymer length and functionality affects bioactivity as long, charged polymers display higher mucoadhesivity than long, neutral polymers or short, charged polymers.     

Functionalization during anionic polymerization of heterocycles

General approaches to the synthesis of functional polymers based on heterocycles are considered. Most attention is paid to the living anionic polymerization with functionalization through initiation or deactivation. It is shown that demands of both high molecular weight and quantitative functionalization cannot be completely satisfied. Some examples of preparing functional polyethers and polyesters are given, namely dinitrophenyl derivatives and vinyl ether macromonomers of poly(ethylene oxide) as well as methacrylate macromonomers of β-propiolactone. Some of perspective applications of these polymers are also touched upon.     

Synthesis of Ferrocene 1,3-Derivatives by Distal C−H Activation**

The third position of cyclopentadienyl ring of a monosubstituted ferrocene has remained as an inaccessible chemical space for direct functionalization. Until recently, functionalizing the C(3)-position while bypassing the predominantly active C(2)-position is the most challenging task. Herein, we report a distal C−H functionalization of monosubstituted ferrocenes using an easily removable directing group with precise site-selectivity, under a Pd^II/ mono-N-protected amino-acid ligand catalytic system. The robust synthetic protocol leads to the synthesis of ferrocene 1,3-derivatives with broad scope in olefins while functionalizing ferrocenyl methylamine in moderate to good yields via a highly strained ferrocene appended 12-membered palladacycle intermediate.     

Functionalization of polymeric organolithium compounds with 3,4‐epoxy‐1‐butene: Precursors for diene‐functionalized macromonomers

The functionalization of polymeric organolithiums (PLi) with 3,4‐epoxy‐1‐butene (EPB) in a hydrocarbon solution yielded the corresponding hydroxybutene‐functionalized polymers in high yields (>95%). Three modes of addition of PLi to EPB were observed (1,4, 3,4, and 4,3). The products and chain‐end structures were characterized by ¹H NMR, ¹³C NMR, attached‐proton‐test ¹³C NMR, calculated ¹³C NMR chemical shifts, and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). The regioselectivity of the addition depended on the PLi chain‐end structure, the reaction conditions, and the addition of lithium salts or Lewis bases. In the absence of additives, the functionalization of poly(styryl)lithium (PSli) produced equal amounts of 1,4‐, 3,4‐, and 4,3‐addition, as determined by quantitative ¹³C NMR analysis. The use of a low temperature (6 °C), inverse addition, the addition of triethylamine (TEA; [TEA]/[PSLi] = 20) as a Lewis base, or dienyllithium chain ends produced polymers with only the 1,4‐addition product. Mild dehydration of the hydroxybutene‐functionalized polymer with p‐toluenesulfonic acid produced the corresponding diene‐functionalized macromonomer, as shown by MALDI‐TOF MS. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 947–957, 2003     

End‐capping of polystyrene by aliphatic primary amine by derivatization of precursor hydroxyl end group

A new and very efficient route for the synthesis of aliphatic primary amine terminated polystyrene (PS) is reported. In contrast to most known methods, only traditional commercially available reagents are used. PS is synthesized by anionic polymerization with a lithium counter ion and the living chains are end‐capped by a hydroxyl group upon addition of ethylene oxide followed by protonation. The ω‐hydroxyl end group is tosylated and the tosylate is then reacted with sodium azide. The azide terminal group is finally reduced into primary amine. The different steps of functionalization have been fully characterized by SEC, ToF‐SIMS, FTIR, and ¹H NMR. The amine content (= 98%) has been determined by acid‐base titration with perchloric acid. It clearly shows the efficiency of the synthetic method reported in this article although it is a multistep method. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1618–1629, 2000     

CONTROLLED ANIONIC SYNTHESIS OF FUNCTIONALIZED AND STAR-BRANCHED POLYMERS

The use of living, alkyllithium-initiated anionic polymerization to prepare chain-end functionalized polymers and heteroarm, star-branched polymers is discussed. The scope and limitations of specific termination reactions with a variety of electrophilic species are illustrated for carbonation, hydroxyethylation, amination, and sulfonation. The methodology of using substituted 1,1-diphenylethylenes to provide a general, quantitative functionalization procedure is outlined and illustrated with examples of amine and phenol end-functionalization. A methodology is described for the synthesis of functionalized, star-branched copolymers with compositionally heterogeneous arms of controlled molecular weight and narrow molecular weight distribution using 1, 3-bis(1-pbenylethenyl) benzene.     

Star-shaped polymers with the fullerene C60 branching center

The anionic methods for the synthesis of homo- and heteroarm (hybrid) star-shaped polymers using fullerene C₆₀ aPre considered. The possibilities of fullerene C₆₀ as an agent of combination of living polymer chains and the procedures of transformation of polymer derivatives of C₆₀ (hexaadducts) into polyfunctional macroinitiators of anionic polymerization of vinyl monomers are shown. The methods for functionalization of polymer fullerene derivatives and their combinations into structures of complex controlled architecture are presented. The structural features and initiating properties of the living polymer fullerene derivatives and their role in the formation of heteroarm star-shaped macromolecules with the controlled number of branches and predetermined molecular weight characteristics of the arms are discussed. The hydrodynamic properties of the star-shaped fullerene-containing polymers are considered. The data on the small-angle neutron scattering study of self-organization of the stars in solutions are presented.     

Anionic methods for synthesis of star polymers

Leading position among numerous methods for synthesis of star polymers is occupied, as regards their potential and diversity, by techniques based on the anionic polymerization. The review considers five basic approaches to application of the anionic polymerization mechanisms in relation to an agent used or procedure employed (methods with polyfunctional coupling agents, multifunctional initiators, polymerizing and nonpolymerizing divinyl agents; multistage methods, methods using C₆₀ fullerene). All groups of syntheses are illustrated by examples, and advantages of methods for synthesis of various homo- and heteroarm star structures are demonstrated. Particular attention is given to syntheses with C₆₀ fullerene. The potential of C₆₀ fullerene as a coupling agent for “living” polymer chains and methods for conversion of polymeric derivatives of C₆₀ (hexaadducts) to polyfunctional macroinitiators of anionic polymerization are described and techniques for functionalization of polymeric fullerene derivatives and their coupling into structures with a complex controllable architecture are presented.     

Selective Reductions of C‐(4,6‐O‐Benzylidene‐β‐d‐glucopyranosyl) Nitromethane

Abstract

The nitromethyl group of C‐(4,6‐O‐benzylidene‐β‐d‐glucopyranosyl) nitromethane was manipulated by various reduction and oxidation methods and further functionalizations into –CH₂NHOH, –CH?NOH, –CN, –CH?O, and –CH₂NHCONH₂, all with retention of the 4,6‐O‐benzylidene group. Certain reduction methods gave rise to a novel secondary amine via an unusual dimeric aminal.     

Trends in polymers functionalized nanostructures for analysis of environmental pollutants

Functional polymers have attached attention in recent years due to their wide applications and unique properties such as sound sensitivity, electrical, catalytic activity, etc for analysis pollutants. The synthesis of functionalized polymers can be affected by several factors, such as the polymerization process, the composition of polymers, and functionalization. However, the scaling-up process from laboratory to industrial is still limited due to its matrix process and steps. We have discussed: i) types of nanostructures and polymer functionalizations, ii) the analytical performance of the functionalized polymers for the analysis of pollutants like toxic gas, pesticide residues, heavy metal, and aromatic compounds, iii) the design and simple concept of the scaling-up process, iv) a parameter affecting the scaling-up process of the synthesis and application of the functionalized polymer nanostructures for the analysis of pollutants. This review will help industry experts and researchers with developing the analysis.     

Formation of primary amines on silicon nitride surfaces: a direct, plasma-based pathway to functionalization

Silicon nitride is the most commonly used passivation layer in biosensor applications where electronic components must be interfaced with ionic solutions. Unfortunately, the predominant method for functionalizing silicon nitride surfaces, silane chemistry, suffers from a lack of reproducibility. As an alternative, we have developed a silane-free pathway that allows for the direct functionalization of silicon nitride through the creation of primary amines formed by exposure to a radio frequency glow discharge plasma fed with humidified air. The aminated surfaces can then be further functionalized by a variety of methods; here we demonstrate using glutaraldehyde as a bifunctional linker to attach a robust NeutrAvidin (NA) protein layer. Optimal amine formation, based on plasma exposure time, was determined by labeling treated surfaces with an amine-specific fluorinated probe and characterizing the coverage using X-ray photoelectron spectroscopy (XPS). XPS and radiolabeling studies also reveal that plasma-modified surfaces, as compared with silane-modified surfaces, result in similar NA surface coverage, but notably better reproducibility.     

Direct Aryl C−H Amination with Primary Amines Using Organic Photoredox Catalysis

The direct catalytic C−H amination of arenes is a powerful synthetic strategy with useful applications in pharmaceuticals, agrochemicals, and materials chemistry. Despite the advances in catalytic C−H functionalization, the use of aliphatic amine coupling partners is limited. Described herein is the construction of C−N bonds, using primary amines, by direct C−H functionalization with an acridinium photoredox catalyst under an aerobic atmosphere. A wide variety of primary amines, including amino acids and more complex amines are competent coupling partners. Various electron‐rich aromatics and heteroaromatics are useful scaffolds in this reaction, as are complex, biologically active arenes. We also describe the ability to functionalize arenes that are not oxidized by an acridinium catalyst, such as benzene and toluene, thus supporting a reactive amine cation radical intermediate.     

FT-IR study on CO<Subscript>2</Subscript> adsorbed species of CO<Subscript>2</Subscript> sorbents

The stability of amine-functionalized silica sorbents prepared through the incipient wetness technique with primary, secondary, and tertiary amino organosilanes was investigated. The prepared sorbents were exposed to different gaseous streams including CO₂/N₂, dry CO₂/air with varying concentration, and humid CO₂/air mixtures to demonstrate the effect of the gas conditions on the CO₂ adsorption capacity and the stability of the different amine structures. The primary and secondary amine-functionalized adsorbents exhibited CO₂ sorption capacity, while tertiary amine adsorbent hardly adsorbed any CO₂. The secondary amine adsorbent showed better stability than the primary amine sorbent in all the gas conditions, especially dry conditions. Deactivation species were evaluated using FT-IR spectra, and the presence of urea was confirmed to be the main deactivation product of the primary amine adsorbent under dry condition. Furthermore, it was found that the CO₂ concentration can affect the CO₂ sorption capacity as well as the extent of degradation of sorbents.     

Thermoresponsive Copolymers of Ethylene Oxide and N,N‐Diethyl Glycidyl Amine: Polyether Polyelectrolytes and PEGylated Gold Nanoparticle Formation

The synthesis of diblock as well as gradient copolymers of N,N‐diethyl glycidyl amine (DEGA) with ethylene oxide (EO) via anionic ring‐opening polymerization is presented. The polymers exhibit low polydispersities (≤1.13) and molecular weights in the range of 3300–10 200 g mol⁻¹. In PEG‐co‐PDEGA copolymers, incorporation of 4%–29% DEGA results in tailorable cloud point temperatures in aqueous solution and melting points depending on DEGA content. mPEG‐b‐PDEGA block copolymers can be quaternized to generate cationic double‐hydrophilic polyelectrolyte copolymers with polyether backbone. Furthermore, mPEG‐b‐PDEGA has been used as dual reducing and capping agent for gold nanoparticle synthesis.     

Photopatterned surfaces for site-specific and functional immobilization of proteins

Photosensitive silanes containing nitroveratryl (Nvoc)-caged amine groups and protein repellent tetraethylene glycol units were synthesized and used for modification of silica surfaces. Functional surface layers containing different densities of caged amine groups were prepared and activated by UV-irradiation of the surface. The performance of these layers for functional and site-selective immobilization of proteins was tested. For this purpose, biotin and tris-nitrilotriacetic acid (tris-NTA) were fist coupled to the activated surface, and the interaction of streptavidin and His-tagged proteins with the functionalized surfaces was monitored by real-time label-free detection. After optimizing the coupling protocols, highly selective functionalization of the deprotected amine groups was possible. Furthermore, the degree of functionalization (and therefore the amount of immobilized protein) was controlled by diluting the surface concentration of the amine-functionalized silane with a nonreactive (OMe-terminated) tetraethylene glycol silane. Immobilized proteins were highly functional on these surfaces, as demonstrated by protein-protein interaction assays with the type I interferon receptor. Protein micropatterns were successfully generated after masked irradiation and functionalization of the caged surface following the optimized coupling protocols.     

Ultrafast organocatalytic ring-opening polymerization of N-sulfonyl aziridine in the melt

An ultrafast approach for controlled synthesis of well-defined polysulfonamides is established through organocatalytic anionic ring-opening polymerization (ROP) of N-sulfonyl aziridine in the melt. Several different organobases are investigated, and it is found that N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) catalyzed ROP of 2-methyl-N-tosylaziridine (TsMAz) gives the desired polymer, while 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) initiate the polymerization along with initiator to produce uncontrolled polymers. Using PMDETA as the catalyst, poly(2-methyl-N-tosylaziridine) with molecular weight over 100 kg/mol can be synthesized in less than 90 s. Various initiators, including carboxylic acid, N-sulfonyl amide, unactivated amine, phenol, and thiol, are applicable for this protocol to give the molecular weight and end-group controlled polymers under the open-flask condition. Combining this ultrafast ROP with ring-opening metathesis polymerization (ROMP), a brush copolymer is facile synthesized. This approach allows the ultrafast metal-free synthesis of polysulfonamide and expands the scope of initiators for the ROP of N-sulfonyl aziridines.     

Directed Evolution of an Iron(II)- and α-Ketoglutarate-Dependent Dioxygenase for Site-Selective Azidation of Unactivated Aliphatic C−H Bonds**

Fe^II- and α-ketoglutarate-dependent halogenases and oxygenases can catalyze site-selective functionalization of C−H bonds via a variety of C−X bond forming reactions, but achieving high chemoselectivity for functionalization using non-native functional groups remains rare. The current study shows that directed evolution can be used to engineer variants of the dioxygenase SadX that address this challenge. Site-selective azidation of succinylated amino acids and a succinylated amine was achieved as a result of mutations throughout the SadX structure. The installed azide group was reduced to a primary amine, and the succinyl group required for azidation was enzymatically cleaved to provide the corresponding amine. These results provide a promising starting point for evolving additional SadX variants with activity on structurally distinct substrates and for enabling enzymatic C−H functionalization with other non-native functional groups.     

New iridium catalysts for the efficient alkylation of anilines by alcohols under mild conditions

The synthesis of eight new iridium complexes containing anionic P,N ligands is described. These complexes have been investigated as catalysts for amine alkylation reactions, resulting in a highly active catalyst for the selective monoalkylation of anilines with primary alcohols, under mild reaction conditions. Nearly quantitative conversion was observed at 70 °C with a catalyst loading as low as 0.05 mol% iridium.