α-H Nitroxides to Prepare Tailored Polymers for Applications in Nanotechnology
• Stereochemistry of Prochiral Radicals coupling with Chiral Nitroxides
(the genesis of TIPNO in Nitroxide-Mediated “Living” Free Radical Polymerization)
• α-H Nitroxides for Controlled Nitroxide-Mediated Radical Polymerization
TIPNO N-alkoxyamine 1 was found to be spectacular at controlling the polymerization of styrenes, acrylates, acrylamides, acrylonitrile (and dienes), to give living polymers with low polydispersity indices (D. Benoit, V. Chaplinski, R. Braslau,* C. J. Hawker * "Development of a Universal Alkoxyamine for 'Living' Free Radical Polymerizations" JACS, 1999, 121, 3904-3920). TIPNO alkoxyamine 1 and the benzyl chloride derivative, and the key nitroxide “TIPNO” (tert-butyl isopropyl phenyl nitroxide) are widely utilized by polymer chemists, and are now sold by Aldrich. The mechanism for the polymerization is shown below:
While studying the inherent enantioselectivity of transient prochiral carbon radicals reacting with persistent chiral nitroxides (Angew. IEE 1997, 36, 237; Tet. Asym. 1997, 8 3209; Tet. Lett. 1996, 37, 7933; Syn. Commun. 2004, 34, 2433), we prepared a series of acyclic α-H nitroxides described in the mid-1990s by Reznikov and Volodarsky, and allowed them to couple with the 1-phenethyl radical.
Although the stereoselectivities were uniformly disappointing, we found that the alkoxyamine products are excellent initiators in “living” free radical polymerization, in a collaboration with Craig Hawker (then at IBM, Almaden, now at UC Santa Barbara).
Polymer Chain End Functionalization
We have synthesized a number of derivatives of TIPNO (Synthesis 2005, 9, 1496):
We have studied the products and mechanism of the thermal decomposition: one of the key properties to the success of these α-hydrogen containing nitroxide in controlled polymerization: A. Nilsen, R. Braslau* "Nitroxide Decomposition," invited “Highlight” article for Journal of Polymer Science Part A: Polymer Chemistry, 2006, 44, 697-717.
The ability to manipulate the polymers can be facilitated by appending specific functional groups at the polymer chain ends.
1. Functionalized "Heads"
Ketone functionalized nitroxide
G. O’Bryan, A. Nilsen, R. Braslau “Ketone Functionalized Nitroxides: Synthesis, Evaluation of
N-Alkoxyamine Initiators, and Derivatization of Polymer Termini” Macromolecules 2007, 40,
7848-7854.
• Cyclic Polymers
1. Cyclic Alkoxyamine Initiator
Bidirectional Initiators
We have developed two types of bidirectional initiators:
1. “Inside-Out” Bidirectional Initiator
Carboxylic Acid functionalized nitroxide
J. Ruehl, C. Morimoto, D. J. Stevens, G. Millhauser, R. Braslau* “Carboxylic Acid and Hydroxy-Functionalized Alkoxyamine Initiators for Nitroxide Mediated Radical Polymerization,” Reactive & Functional Polymers 2008, 68, 1563-1577.
Primary Alcohol functionalized nitroxide
J. Ruehl, C. Morimoto, D. J. Stevens, G. Millhauser, R. Braslau* “Carboxylic Acid and Hydroxy-Functionalized Alkoxyamine Initiators for Nitroxide Mediated Radical Polymerization,” Reactive & Functional Polymers 2008, 68, 1563-1577.
Oxidative Alkoxyamine Cleavage with CAN
The nitroxide group can be removed following polymerization upon treatment with CAN. For polystyrenes, the transient terminal benzylic cation can be trapped with nucleophiles to afford semitelechelic polymers. Addition of a catalytic amount of TEMPO to aqueous mixtures affords ketone terminated polymers.
G. O’Bryan, R. Braslau* “Terminal Functionalization of Polymers via Single Electron Oxidation of N-Alkoxyamines,” Macromolecules, 2006, 39, 9010-9017.
Thermolytic nitroxide exchange: addition to enol ethers
We have developed a post-polymerization thermolysis method using a “chain transfer agent” to introduce a ketone onto the polymer terminus. W. Chau; R. Turner; R. Braslau* “Ketone ω-Functionalization of Polymers Prepared by Nitroxide-Mediated Polymerization via Addition to a Benzyl Enol Ether” Reactive & Functional Polymers 2008, 68, 396-405.
Exchange of Nitroxide for Azide
Using the reagent ethylsulfonyl azide, developed by Renaud, polystyrenes undergo end-group functionalization to give azide-terminated polymers, ideal for use in copper catalyzed Huisgen [1,3] dipolar cycloaddition (“Click Chemistry”). G. O’Bryan, N. Ningnuek, R. Braslau* “Cyclization of α−ω Heterotelechelic Polystyrene Prepared by Nitroxide-Mediated Radical Polymerization” Polymer 2008, 49, 5241-5248.
2. Functionalized "Feet"
We have developed synthetic routes to convert the readily available benzyl chloride initiator into a variety of functionalized initiators including thiol and disulfide initiators: N. L. Hill, J. L. Jarvis, F. Pettersson, R. Braslau "Synthesis of Thiol-Derivatized Initiators for Nitroxide-Mediated Radical Polymerization: Reversible Disulfide Formation" Reactive & Functional Polymers 2008, 68, 361-368, as well as azide, amine, benzyl alcohol and carboxylic acid-derivatized initiators: N. L. Hill; R. Braslau “Synthesis of Arylethyl Functionalized N-Alkoxyamine Initiators and use in Nitroxide-Mediated Radical Polymerization” Journal of Polymer Science Part A: Polymer Chemistry, 2007, 45, 2341-2349.
This initiator is indeed “living” at both ends, and is useful in the preparation of amphiphilic ABA triblock copolymers. In the presence of a diamine, these amphiphiles self-assemble into discrete particles: J. Ruehl; A. Nilsen; S. Born; P. Thoniyot; L. Xu; S. Chen; R. Braslau “Nitroxide-Mediated Polymerization to Form Symmetrical ABA Triblock Copolymers from a Bidirectional Alkoxyamine Initiator” Polymer 2007, 48(9), 2564-2571.
AFM images of (A) PAA8-b-PS19-b-PAA8, (B) PAA24-b-PS67-b-PAA24, and (C) PAA17-b-PnBA19-b-PAA17
2. “Outside-In” Bidirectional Initiator
We have designed and synthesized a central bisnitroxide to form an initiator that adds new monomers at the middle of the growing polymer chain:
This bidirectional initiator performs beautifully, forming very controlled homopolymers, as well as excellent triblock copolymers (N. Hill, R. Braslau “Synthesis and Characterization of a Novel Bisnitroxide Initiator for Effecting “Outside-In” Polymerization” Macromolecules, 2005, 38, 9066-9074). Interestingly, it effects polymerizations at a much faster rate than either the monodirectional initiator, or the “inside-out” initiator, effecting polymerizations at temperatures as low as 70° C. Low temperature EPR studies indicate a very strong spin-spin interaction for the bisnitroxide: the nitroxide moieties are about 5 Å apart. This supports a resonance-stabilized delocalization of the key polymerization intermediate. J. Ruehl, N. L. Hill, E. D. Walter, G. Millhauser, R. Braslau* “A proximal bisnitroxide initiator: Studies in low-temperature nitroxide-mediated polymerizations” Macromolecules 2008, 41, 1972-1982, and J. K. Ruehl; R. Braslau* “A Bidirectional ATRP-NMRP Initiator: The Effect of Nitroxide Size on the Rate of Nitroxide-Mediated Polymerization” Journal of Polymer Science Part A: Polymer Chemistry, 2007, 45, 2015-2025.
Cyclic alkoxyamine initiators have been investigated to prepare cyclic polymers. The 17-membered ring initiator (prepared by Grubbs RCM) forms oligomeric polymers with several alkoxyamines stitched together, whereas the 5-membered ring initiator gives uncontrolled polymerization. EPR studies confirm that the 5-membered cyclic alkoxyamine does not dissociate to form a nitroxide species, whereas the 17-membered cyclic alkoxyamine does dissociate to form nitroxide, but the rate of dissociation is slower than that of parent TIPNO-based alkoxyamine. J. Ruehl, N. Ningnuek, T. Thongpaisanwong, R. Braslau* “Cyclic Alkoxyamines for Nitroxide Mediated Radical Polymerization,” Journal of Polymer Science Part A: Polymer Chemistry, 2008, 49, 8049-8069.
2. Post-polymerization “Click” Reaction to form Macrocycles
Using our CAN-mediated oxidative removal of the nitroxide polymer “head” by trapping with propargyl alcohol, and azide functionalization of the “foot,” we have utilized the popular “Click Reaction” to prepare cyclic polymers under high dilution: G. O’Bryan, N. Ningnuek, R. Braslau* “Cyclization of α−ω Heterotelechelic Polystyrene Prepared by Nitroxide-Mediated Radical Polymerization” Polymer 2008, 49, 5241-5248.
Nitroxide-mediated precipitation polymerizations of styrene in supercritical carbon dioxide (scCO2, a green solvent) is being investigated as a collaboration with the group of Fawaz Aldabbagh in Galway, Ireland. We have synthesized three fluorinated TIPNO alkoxyamine initiators: two with the mediating nitroxide bearing the fluorous tag, and the last with a fluorinated phenethyl "foot." Polymerizations in scCO2 did not display a significant difference vs. polymerization in toluene. C. Magee, A Earla, J. Petraitis, C. Higa, R. Braslau,* P. B. Zetterlund,* F. Aldabbagh* “Synthesis of Fluorinated Alkoxyamines and Alkoxyamine-Initiated Nitroxide-Mediated Precipitation Polymerizations of Styrene in Supercritical Carbon Dioxide,” Polymer Chemistry, 2014, 5, 5725-5733. doi: 10.1039/c4py00757c
We are now generating a tunable macroinitiator bearing multiple fluorous tags to determine the fluorous content necessary to ensure significant partioning into the scCO2 phase.
