Tamaz Guliashvili

Mechanism of Carbon-Halogen Bond Reductive Cleavage in Activated Alkyl Halide Initiators Relevant to Living Radical Polymerization: Theoretical and Experimental Study

The mechanism of reductive cleavage of model alkyl halides (methyl 2-bromoisobutyrate, methyl 2-bromopropionate, and 1-bromo-1-chloroethane), used as initiators in living radical polymerization (LRP), has been investigated in acetonitrile using both experimental and computational methods. Both theoretical and experimental investigations have revealed that dissociative electron transfer to these alkyl halides proceeds exclusively via a concerted rather than stepwise manner. The reductive cleavage of all three alkyl halides requires a substantial activation barrier stemming mainly from the breaking C-X bond. The activation step during single electron transfer LRP (SET-LRP) was originally proposed to proceed via formation and decomposition of RX(•-) through an outer sphere electron transfer (OSET) process (Guliashvili, T.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 1607). These radical anion intermediates were proposed to decompose via heterolytic rather than homolytic C-X bond dissociation. Here it is presented that injection of one electron into RX produces only a weakly associated charge-induced donor-acceptor type radical anion complex without any significant covalent σ type bond character between carbon-centered radical and associated anion leaving group. Therefore, neither homolytic nor heterolytic bond dissociation applies to the reductive cleavage of C-X in these alkyl halides inasmuch as a true radical anion does not form in the process. In addition, the whole mechanism of SET-LRP has to be revisited since it is based on presumed OSET involving intermediate RX(•-), which is shown here to be nonexistent.

Ambient temperature rapid SARA ATRP of acrylates and methacrylates in alcohol–water solutions mediated by a mixed sulfite/Cu(II)Br2 catalytic system

The new generation of catalytic systems for Controlled/“Living” Radical Polymerization (CLRP) of vinyl monomers should be non-toxic, inexpensive and provide fast polymerizations in environmentally friendly media. Herein, we report the successful ambient temperature ATRP of several vinyl monomers (MA, n-BA, MMA and DMAEMA) catalyzed by inorganic sulfites (Na2S2O4 and Na2S2O5) and small amounts of a Cu(II)Br2/Me6TREN system in alcohol–water mixtures. The controlled character of ATRP of acrylates and methacrylates was confirmed by the linear increase of molecular weights with monomer conversion, narrow molecular weight distributions (Mw/Mn ∼ 1.05) and by reinitiation experiments (copolymerization and chain extension). 1H NMR and MALDI-TOF analyses confirmed the molecular structure and chain-end functionality of the obtained polymers. ATRP of MA using this novel catalytic system in alcohol–water mixtures with multifunctional Br-based initiators provides 4 and 6 arm star polyacrylates in a controlled manner without any observable gel formation. The data presented open up the possibility of using fast ATRP catalyzed by inorganic sulfites (approved by FDA as food and beverage additives) in solvents that are inexpensive, eco-friendly and widely used in chemical industrial processes.

Improvement of the control over SARA ATRP of 2-(diisopropylamino)ethyl methacrylate by slow and continuous addition of sodium dithionite

The kinetics and detailed mechanism of SARA ATRP of 2-(diisopropylamino)ethyl methacrylate (DPA) were investigated. Supplemental activator and reducing agent (SARA) atom transfer radical polymerization (ATRP) using sodium dithionite (Na2S2O4) was used to create well controlled polymers of PDPA. The influence of the initiator, solvent, structure and concentration of the catalyst was studied, and the ratios of Na2S2O4 were adjusted to optimize the polymerization. Well controlled polymers required Na2S2O4 to be slowly and continuously fed to the reaction mixture, with 500 parts per million (ppm) of CuBr2 with tris(2-dimethyamino)amine (Me6TREN) as a ligand. The initial content of Na2S2O4 in the reaction mixture, the feeding rate and the Cu catalyst concentration were optimized to provide polymers with narrow molecular weight distribution (Mw/Mn < 1.15) at high monomer conversion (∼90%). Interestingly, the results revealed that when tris(2-pyridylmethyl)-amine (TPMA) was used as a ligand, the amount of copper required to achieve similar control of the polymerization could be decreased 5 times. This system was successfully extended to the polymerization of oligo(ethylene oxide) methyl ether methacrylate (OEOMA). The high conversion and preservation of the chain-end functionality allows the direct synthesis of POEOMA-b-PDPA block copolymers. The low catalyst concentrations and benign nature of Na2S2O4 make this SARA ATRP method attractive for the synthesis of well controlled water soluble polymers for biomedical applications.

Synthesis of cationic poly((3-acrylamidopropyl)trimethylammonium chloride) by SARA ATRP in ecofriendly solvent mixtures

Supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) of the cationic monomer (3-acrylamidopropyl)trimethylammonium chloride (AMPTMA) was successfully performed for the first time. The polymerizations were performed in water or ethanol–water mixtures at room temperature in the presence of Cu(0), using relatively low concentrations of soluble copper catalyst and an excess of ligand (Me6TREN). The reaction conditions were optimized to give the best control over the polymerization under environmentally friendly conditions. The polymerization data showed good control over the molecular weights with narrow molecular weight distributions for the entire polymerization. The preservation of the chain-end functionality was confirmed by self-chain extension and the synthesis of a block copolymer containing AMPTMA and oligo(ethylene oxide) methyl ether acrylate (OEOA). SARA ATRP was also extended to the synthesis of alkyne-terminated poly-AMPTMA (PAMPTMA), which was subsequently functionalized, using copper(I) catalyzed azide–alkyne cycloaddition, with an azido-functionalized coumarin derivative.

Synthesis of well-defined functionalized poly(2-(diisopropylamino)ethyl methacrylate) using ATRP with sodium dithionite as a SARA agent

2-(Diisopropylamino)ethyl methacrylate (DPA) was polymerized by Atom Transfer Radical Polymerization (ATRP) using sodium dithionite (Na2S2O4) as a reducing agent and supplemental activator with a Cu(II)Br2/Me6TREN catalytic system at 40 °C in an isopropanol–water mixture. The effects of the solvent mixture and the initiator structure on the polymerization kinetics were studied. The eco-friendly catalytic system described is suitable for the synthesis of poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) with controlled molecular weight, low dispersity, and well-defined chain-end functionality. Both linear and 4-arm star polymers with various target molecular weights were synthesised. The 1H NMR and MALDI-TOF analyses confirmed the molecular structure and high chain-end functionality of the obtained polymers. The use of an alkyne functionalized initiator allowed further azide–alkyne Huisgen cycloaddition with 3-azido-7-diethylamino-coumarin, a fluorescent biocompatible molecule.

Synergistic Effect of 1‑Butyl-3-methylimidazolium Hexafluorophosphate and DMSO in the SARA ATRP at Room Temperature Affording Very Fast Reactions and Polymers with Very Low Dispersity

An unusual synergistic effect between 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM-PF6) and dimethyl sulfoxide (DMSO) mixtures is reported for the supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) of methyl acrylate (MA) using a catalytic system composed by sodium dithionate (Na2S2O4) and CuBr2/Me6TREN (Me6TREN: tris[2-(dimethylamino)ethyl]amine) at room temperature. To the best of our knowledge, the use of ionic liquids (IL) has never been reported for the SARA ATRP. The kinetic data obtained for a broad range of target molecular weights revealed very fast polymerization rates, low dispersity values (Đ < 1.05) and well-defined chain-end functionalities.

Getting faster: low temperature copper-mediated SARA ATRP of methacrylates, acrylates, styrene and vinyl chloride in polar media using sulfolane/water mixtures

Supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) of acrylates, methacrylates, styrene and vinyl chloride was successfully performed in sulfolane/water mixtures using ppm amounts of soluble copper. The catalytic effect of the presence of water in the reaction mixtures resulted in a notable acceleration of the polymerization of the different monomers studied. The first-order kinetics with monomer conversion and the low dispersity values (Đ) of the polymers revealed the controlled features of the polymerization. As a proof-of-concept, an ABA block copolymer of poly(methyl acrylate)-b-poly(vinyl chloride)-b-poly(methyl acrylate) was prepared, confirming also the “living” character of the polymers. The results presented in this contribution extend the importance of sulfolane as an universal industrial solvent for the SARA ATRP of a broad range of monomer families by significantly enhancing the polymerization rate, due to the selective addition of water to the solvent mixture. The incorporation of small amounts of water in the solvent mixture has also allowed the use of FDA-approved sulfites as the SARA agent, which was not possible using pure sulfolane as the polymerization solvent.

Synthesis of functionalized poly(vinyl acetate) mediated by alkyne-terminated RAFT agents

Two new xanthates with alkyne functionalities were synthesized for the reversible addition fragmentation chain transfer (RAFT) polymerization of vinyl acetate (VAc). The new RAFT agents were fully characterized by 1H and 13C NMR spectroscopy. Unlike the alkyne terminated RAFT agent (AT-X1) the protected alkyne-terminated RAFT agent (PAT-X1) was able to conduct the RAFT polymerization of VAc with a good control over the molecular weight (MW) and relatively narrow MW distributions (Đ < 1.4). The linear evolution of Mn with conversion as well as the close agreement between Mn,th and Mn,GPC values confirmed the controlled features of the RAFT system. It is worth mentioning that the polymer dispersity remained very low (Đ < 1.20) until relatively high monomer conversions (60%) due to the non-activated nature of VAc. The chain end-functionality of the obtained polymers was evaluated by 1H NMR, FTIR-ATR and UV-Vis absorption analysis. The “livingness” of the obtained polymer was confirmed by a successful chain extension experiment. The deprotection of the alkyne functionality in the PVAc, allowed a further copper catalyzed azide–alkyne [3 + 2] dipolar cycloaddition reaction (CuAAC) with an azido terminated-poly(ethylene glycol) (PEG-N3), to afford PVAc–PEG block-copolymers as a proof-of-concept.

Unsuccessful attempts to add alcohols to transient 2-amino-2-siloxy-silenes - leading to a new benign route for base-free alcohol protection

Thermolytic formation of transient 1,1-bis(trimethylsilyl)-2-dimethylamino-2-trimethylsiloxysilene (2) from N,N-dimethyl(tris(trimethylsilyl)silyl)methaneamide (1) in presence of a series of alcohols was investigated. The products are, however, not the expected alcohol-silene addition adducts but silylethers formed in nearly quantitative yields. Thermolysis of 1 in the presence of both alcohols (MeOH or iPrOH) and 1,3-dienes (1,3-butadiene or 2,3-dimethyl-1,3-butadiene) gives alkyl-tris(trimethylsilyl)silylethers and the [4+2] cycloadducts between the silene and diene, which confirms the presence of 2 and that it is unreactive towards alcohols. The observed silylethers are substitution adducts where the amide group of the silylamide is replaced by an alkoxy group, and the reaction time is reflected in the steric bulk of the alcohol. Indeed, the formation of silylethers from the reaction of alcohols with silylamide represents a new base-free method for protection of alcohols. The protection reactions using 1 progresses at elevated temperatures, or alternatively, under acid catalysis at ambient temperature, and similar protections can be carried out with N-cyclohexyl(triphenylsilyl)methaneamide and N,N-dimethyl(trimethylsilyl)methaneamide. The latter silylamide can be used under neutral conditions at room temperature. The only by-products are formamides (N,N-dimethylformamide (DMF) or N-cyclohexylformamide), and the reactions can be performed without solvent. In addition to alcohols we also examined the method for protection of diols, thiols and carboxylic acids, and also these reactions proceeded in high yields and with good selectivities.

Computational Evaluation of the Sulfonyl Radical as a Universal Leaving Group for RAFT Polymerisation

The present study investigates the performance of the sulfonyl radical, i.e. •SO2Ph, as a universal leaving group in reversible addition–fragmentation chain-transfer (RAFT) polymerisation. The sulfonyl radical is widely used as a radical initiator and has already been proved successful as a leaving group in an atom-transfer radical polymerisation. Our results, obtained using high-level ab initio computational methodology under relevant experimental conditions, indicate superior performance of the sulfonyl compared with a reference cyanoisopropyl group in controlling RAFT of a wide range of monomers. Importantly, the presence of sulfonyl chain ends in the polymers so formed opens attractive possibilities for further functionalisation. Potential synthetic routes to the R-sulfonyl RAFT agents are discussed.