Smart Control of Nitroxide-Mediated Polymerization Initiators' Reactivity by pH, Complexation with Metals, and Chemical Transformations

Abstract

Because alkoxyamines are employed in a number of important applications, such as nitroxide-mediated polymerization, radical chemistry, redox chemistry, and catalysis, research into their reactivity is especially important. Typically, the rate of alkoxyamine homolysis is strongly dependent on temperature. Nonetheless, thermal regulation of such reactions is not always optimal. This review describes various ways to reversibly change the rate of C⁻ON bond homolysis of alkoxyamines at constant temperature. The major methods influencing C⁻ON bond homolysis without alteration of temperature are protonation of functional groups in an alkoxyamine, formation of metal⁻alkoxyamine complexes, and chemical transformation of alkoxyamines. Depending on the structure of an alkoxyamine, these approaches can have a significant effect on the homolysis rate constant, by a factor of up to 30, and can shorten the half-lifetime from days to seconds. These methods open new prospects for the application of alkoxyamines in biology and increase the safety of (and control over) the nitroxide-mediated polymerization method.

Keywords: alkoxyamine; complexation; nitroxide mediated polymerization; protonation; tunable rate constants.

Figure 1

(a) The scheme of alkoxyamine hemolysis; (b) An outline of a smart alkoxyamine. Reproduced/Adapted from Ref. [18] with permission from The Royal Society of Chemistry.

Figure 2

The influence of introduction of electron-withdrawing groups and electron-donating groups into the alkyl and nitroxyl part of an alkoxyamine on the polarity of the C–ON bond and thus the rate of homolysis.

Figure 3

Structure of alkoxyamine 1 and RAFT agent 2 first used for pH-switchable controlled radical polymerization.

Figure 4

(a) Structures of alkoxyamines 3–9; (b) Protonation of 3 and (c) deprotonation of 9.

Figure 5

(a) ¹H NMR spectra of 10 (in D₂O) recorded at solution pH levels 10.0, 5.3, and 2.0 with signal attribution as indicated in the structure; (b) Titration curves obtained from signals b (□) and c,c’ (■, ●) (see signal attribution) with a fit, and the values of pK_a for pyridine and amidine functions; (c) Kinetics of homolysis of alkoxyamine 10 (0.02 M solution) at 368 K as determined by ¹H NMR in the presence of 40 eq. of ascorbic acid or ascorbate at different pH levels. Adapted with permission from Ref. [30]. Copyright 2011 American Chemical Society.

Figure 6

Structures of alkoxyamines 10–13.

Figure 7

Logarithms of equilibrium constants for NO–C bond homolysis (a combination is defined as the forward reaction, and decomposition as the reverse one) obtained from the bond dissociation free energies for the tested nitroxides with a styryl dimer as a propagating radical, calculated for a bulk styrene solution at 25 and 120 °C. The green line corresponds to log K = 12 (corresponds to the TEMPO-Sty alkoxyamine used as a reference). Structures of only the anionic forms are depicted. Adapted from Ref. [33] with permission from the PCCP Owner Societies.

Figure 8

Protonated forms of alkoxyamine 10. Polymerization of styrene at 140 °C initiated by protonated or deprotonated forms of alkoxyamine 10. The monomer-to-initiator ratio is 1000/1. (a) A kinetics plot for polymerization; lines: a linear fit of the experimental data points; (b) Evolution of molecular weight and dispersity. ■: pure alkoxyamine, form II; ●: alkoxyamine in the presence of 1 eq. of CF₃COOH, form III; ▲: alkoxyamine in the presence of 10 eq. of CF₃COOH, form IV. The solid line denotes the theoretical M_n, dashed lines: a linear fit of the experimental data points. Adapted with permission from Ref. [30]. Copyright 2011 American Chemical Society.

Figure 9

Structures of bis(hexafluoroacetylacetonate) zinc complexes with alkoxyamines 3 and 4 according to X-ray diffraction data: (a) the ring-type complex, (b) chain-type complex, and (c) intramolecular complex. The structure of the complex depends strongly on the diastereomeric configuration of the alkoxyamine.

Figure 10

(a) Room temperature data on ³¹P NMR spectroscopy at 0, 1, 6, and 12 equivalents of pyridine (from the bottom up) added to Cu-RSSR-3 in C₆D₆ (the asterisk denotes free (RS/SR)-3 as an impurity) and data on pure 3-RRSS; (b) Kinetics of Cu-RSSR-3 decomposition in the presence of 3 eq. of TEMPO after gradual addition of pyridine (py) as a competitor. Adapted from Ref. [44] with permission from The Royal Society of Chemistry.

Figure 11

M_n versus conversion, PDI vs. conversion, and ln([M]/[M]₀) vs. time plots for (a) the polymerization of styrene at 90 °C initiated with RS/SR-3 (★), Zn-RSSR-3 (■), Zn-RSSR-3’ (RS/SR-3 + 0.5 eq. Zn(hfac)₂) (*), or 3 + 10 eq. Zn(hfac)₂ (○); the monomer to initiator ratio is 250:1.

Figure 12

Structures of alkoxyamine 3 derivatives. Adapted with permission from Ref. [51]. Copyright 2012 American Chemical Society.

Figure 13

Enzymatic hydrolysis of 27 into 28H, protonated as 28H⁺ at pH 7.2, and its subsequent spontaneous homolysis into an alkyl radical and nitroxide.

Figure 14

The reaction of 1,3-dipolar cycloaddition of olefin that takes place simultaneously during the initiation of nitroxide-mediated polymerization (NMP).

Figure 15

Kinetics of inactive alkoxyamine decomposition under various conditions. (a) Black squares: pure inactive alkoxyamine 29, white squares: 6 eq. of styrene, crossed squares: 33 eq. of styrene, half-colored squares: presynthesized with styrene alkoxyamine. (b) Black squares: pure inactive alkoxyamine, white squares: 33 eq. of styrene, white stars: 30 eq. of MMA, white triangles: 30 eq. of acrylonitrile, white circles: 35 eq. of butyl acrylate. Red lines: a linear fit of experimental data points. The temperature in all experiments is 373 K. The solvent is C₆D₄Cl₂. Adapted from Ref. [52] with permission from The Royal Society of Chemistry.

Figure 16

Structure of alkoxyamine 30.

Figure 17

Cartoon representation of the impact of a solvent on an intimate ion pair. Reprinted with permission from Ref. [51]. Copyright 2013 American Chemical Society.

Figure 18

Various types of intramolecular hydrogen bonds (IHBs): (a) within the nitroxyl moiety (intraN); (b) within the alkyl part (intraR); (c) from an alkyl to nitroxyl part (interR); and (d) from a nitroxyl to alkyl part (interN). Dotted lines represent an IHB. (e) Structures of alkoxyamines 31–33.

Figure 18

Various types of intramolecular hydrogen bonds (IHBs): (a) within the nitroxyl moiety (intraN); (b) within the alkyl part (intraR); (c) from an alkyl to nitroxyl part (interR); and (d) from a nitroxyl to alkyl part (interN). Dotted lines represent an IHB. (e) Structures of alkoxyamines 31–33.