U.S. patent application number 12/877589 was filed with the patent office on 2011-03-10 for preparation of functional polymers.
This patent application is currently assigned to Carnegie Mellon University. Invention is credited to Krzysztof Matyjaszewski, James Spanswick, Brent S. Sumerlin, Nicolay V. Tsarevsky.
Application Number | 20110060107 12/877589 |
Document ID | / |
Family ID | 34975533 |
Filed Date | 2011-03-10 |
United States Patent
Application |
20110060107 |
Kind Code |
A1 |
Matyjaszewski; Krzysztof ;
et al. |
March 10, 2011 |
PREPARATION OF FUNCTIONAL POLYMERS
Abstract
The process of the present invention is directed toward
conducting highly selective, high yield post polymerization
reactions on polymers to prepare functionalized polymers. An
embodiment of the present invention comprises conducting click
chemistry reactions on polymers. Preferably, the polymers were
prepared by controlled polymerization processes. Therefore,
embodiments of the present invention comprise processes for the
preparation of polymers comprising conducting a click chemistry
reaction on a functional group attached to a polymer, wherein the
polymer has a molecular weight distribution of less than 2.0. The
functional polymers may be prepared by converting an attached
functional unit on the polymer thereby providing site specific
functional materials, site specific functional materials comprising
additional functionality, or chain extended functional materials.
Embodiments of the process of the present invention include
functionalization reactions, chain extensions reactions, to form
block copolymer linking reactions, and attaching side chains to
form graft copolymers, for example.
Inventors: |
Matyjaszewski; Krzysztof;
(Pittsburgh, PA) ; Sumerlin; Brent S.;
(Pittsburgh, PA) ; Tsarevsky; Nicolay V.;
(Pittsburgh, PA) ; Spanswick; James; (Wheaton,
IL) |
Assignee: |
Carnegie Mellon University
Pittsburgh
PA
|
Family ID: |
34975533 |
Appl. No.: |
12/877589 |
Filed: |
September 8, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10591425 |
Jun 22, 2007 |
7795355 |
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PCT/US05/07264 |
Mar 7, 2005 |
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12877589 |
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Current U.S.
Class: |
525/196 ;
525/326.7 |
Current CPC
Class: |
C08F 293/005 20130101;
C08F 8/30 20130101; C08F 2438/03 20130101; C08F 2438/01
20130101 |
Class at
Publication: |
525/196 ;
525/326.7 |
International
Class: |
C08F 8/30 20060101
C08F008/30 |
Claims
1.-20. (canceled)
21. A process for the preparation of polymers, comprising:
conducting a click chemistry reaction on a functional group
attached to a functional polymer, wherein the polymer has a
molecular weight distribution of less than 2.0.
22. The process of claim 21, further comprising: reacting a
terminal group on a first polymer with a compound to form the
functional polymer comprising groups capable of reacting in the
click chemistry reaction; and wherein conducting a click chemistry
reaction results in chain extending the functional polymers to form
a higher molecular weight polymer.
23. The process of claim 22, wherein the click chemistry reaction
results in the formation of linear polymers with distributed
functionality.
24. The process of claim 23, wherein the distributed functionality
comprises a degradable functionality.
25. The process of claim 23, wherein the linear polymer is a block
copolymer comprising two or more segments of different
composition.
26. The process of claim 22, wherein the click chemistry reaction
results in the formation of graft copolymer.
27. The process of claim 22, wherein the click chemistry reaction
results in the formation of a graft copolymer tethered to a
polymer, particle or a substrate.
28. The process of claim 22, further comprising preparing the first
polymer by a controlled radical polymerization process.
29. The process of claim 22, wherein terminal groups comprise an
acetylene bond or an azido-group.
30. The process of claim 22, wherein the functional group attached
to the functional polymer is a nitrile group and conducting a click
chemistry reaction on a nitrile group results in formation of an
azole functionality.
31. The process of claim 21, wherein the functional group attached
to the functional polymer is one of an azido group, acetylenic
amino group, and phosphino group.
32. The process of claim 21, wherein the click chemistry reaction
comprises a dipolar cycloaddition reaction with triple bonded
functional groups.
33. The process of claim 32, wherein the triple bonded functional
groups comprise alkynes and nitrites and result in the formation of
substituted triazoles or tetrazoles.
34. The process of claim 21, wherein conducting the click chemistry
reaction results in the addition of a functional group selected
from amino, primary amino, hydroxyl, sulfonate, benzotriazole,
bromide, chloride, chloroformate, trimethylsilane, phosphonium
bromide or bio-responsive functional group including polypeptides,
proteins and nucleic acids to the polymer.
35. The process of claim 21, further comprising: reacting a
terminal group on the first polymer with a compound to form a
polymer comprising groups capable of reacting in a click chemistry
reaction, wherein the polymer has a molecular weight distribution
of less than 2.0; and conducting a click chemistry reaction
resulting in a ring closing reaction to form a macrocyclic
polymer.
36. The process of claim 21, wherein the attached functional groups
are telechelic functionality, site specific functionality,
functionality dispersed along a polymer backbone or blocks of
monomers comprising the functional group.
37. The process of claim 36, wherein the click chemistry reaction
include reactions systems comprising multiple click chemistry
reactions involving different reactive functional groups.
38. The process of claim 37, wherein the click chemistry reactions
include reactions selected from the group consisting of a
hydrosilation reaction of H--Si and simple non-activated vinyl
compounds, urethane formation from alcohols and isocyanates, a
[2+3] cycloaddition of alkyl azides and acetylenes, a Menshutkin
reaction of tertiary amines with alkyl iodides or alkyl
trifluoromethanesulfonates, a Michael addition reaction, a
maleimide-thiol reaction, atom transfer radical addition reactions
between --SO.sub.2Cl and an olefin, a metathesis reaction, a
Staudinger reaction of phosphines with alkyl azides, and oxidative
coupling of thiols.
39. The process of claim 38, wherein a first attached functional
group comprises an acetylene bond, an azido-group, a nitrile group,
an acetylenic group, an amino group, or a phosphino group.
40. The process of claim 37, wherein the multiple click chemistry
reactions are selected to form a polymeric structure selected from
the group consisting of linear multisegmented block copolymers,
graft copolymers, star copolymers, brush copolymers, two or more
polymers tethered to a substrate, dendritic or hyperbranched
copolymers, and network structures.
Description
TECHNICAL FIELD OF THE INVENTION
[0001] This invention is directed to a process for preparation and
use of oligomers and polymers with attached functionality and is
also directed to oligomers and polymers produced by the process.
Embodiments of the process of the present invention include
reacting a polymer with attached functional groups in a high-yield
post-polymerization reaction, such as a click chemistry reaction.
The attached functional groups may be, for example, telechelic
functionality, site specific functionality, functionality dispersed
along a polymer backbone or blocks of monomers comprising the
functionality.
BACKGROUND OF THE INVENTION
[0002] Polymers with attached functional groups may be prepared
directly by polymerization of functional monomers. Oligomers and
polymers prepared by a controlled polymerization processes may have
functionality at specific locations along the chain and a specific
amount of functionality. For example, functional monomers may be
placed periodically along the polymer chain, the initiator may have
attached functionality, or the group providing for controlled
polymerization may be removed and replaced with a desired
functional group. However, there are several controlled
polymerization processes and many functional monomers may not be
directly copolymerized by every controlled polymerization process.
Further, the monomers with desired functionality may not
copolymerize in the desired manner using the selected controlled
polymerization process. For instance, non-radical based
polymerization processes are not as robust as radical
polymerization processes, i.e., the polymerization processes are
not able to tolerate a wide range of monomer functionality.
[0003] Controlled radical polymerization ("CRP") processes have
been described by a number of workers in three ACS Symposium Series
edited by Professor Matyjaszewski. [ACS Symp. Ser. Vol. 685, 1998;
Vol. 768, 2000; and Vol. 854, 2003.] The use of a CRP for the
preparation of an oligo/polymeric material allows control over the
molecular weight, molecular weight distribution of the (co)polymer,
topology, composition and functionality of a polymeric material.
The topology can be controlled allowing the preparation of linear,
star, graft or brush copolymers, formation of networks or dendritic
or hyperbranched materials and can include such materials grown
from any type of solid surface. Composition can be controlled to
allow preparation of homopolymers, periodic copolymers, block
copolymers, random copolymers, statistical copolymers, gradient
copolymers, and graft copolymers. In a gradient copolymer, the
gradient of compositional change of one or more comonomers units
along a polymer segment can be controlled by controlling the
instantaneous concentration of the monomer units in the
copolymerization medium, for example. Molecular weight control is
provided by a process having a substantially linear growth in
molecular weight of the polymer with monomer conversion accompanied
by essentially linear semilogarithmic kinetic plots for chain
growth, in spite of any occurring terminations. Polymers from
controlled polymerization processes typically have molecular weight
distributions, characterized by the polydispersity index ("PDI"),
of less than or equal to 2, The PDI is defined by the ratio of the
weight average molecular weight to the number average molecular
weight, M.sub.w/M.sub.n. More preferably in certain applications,
polymers produced by controlled polymerization processes have a PDI
of less than 1.5, and in certain embodiments, a PDI of less than
1.3 may be achieved.
[0004] Further functionality may be placed on the oligo/polymer
structure including side-functional groups, end-functional groups
providing homo- or hetero-telechelic materials or can comprise site
specific functional groups, or multifunctional groups distributed
as desired within the structure. The functionality can be dispersed
functionality or can comprise functional segments. The composition
of the polymer may comprise a wide range of radically
(co)polymerizable monomers, thereby allowing the bulk or surface
properties of a material to be tailored to the application.
Materials prepared by other processes can be incorporated into the
final structure as macromonomers, macroinitiators, or as other
tele-functional materials or as substrates for CRP processes in
either grafting from or grafting to processes. The term
tele-functional material includes the materials normally considered
to be macromonomers and macroinitiators but is used herein to
indicate that other chain end functional materials can now be
incorporated into a target structure by consideration of the
terminal functionality and target coupling or linking reaction.
[0005] Polymerization processes performed under controlled
polymerization conditions achieve these properties by consuming the
initiator early in the polymerization process and, in at least one
embodiment of controlled polymerization, an exchange between an
active growing chain and dormant polymer chain that is equivalent
to or faster than the propagation of the polymer. A CRP process is
a process performed under controlled polymerization conditions with
a chain growth process by a radical mechanism, such as, but not
limited to; ATRP, stable free radical polymerization (SFRP),
specifically, nitroxide mediated polymerization (NMP), reversible
addition-fragmentation transfer (RAFT), degenerative transfer (DT),
and catalytic chain transfer (CCT) radical systems. A feature of
controlled radical polymerizations is the existence of equilibrium
between active and dormant species. The exchange between the active
and dormant species provides a slow chain growth relative to
conventional radical polymerization, all polymer chains grow at the
same rate, although overall rate of conversion can be comparable
since often many more chains are growing. Typically, the
concentration of radicals is maintained low enough to minimize
termination reactions. This exchange, under appropriate conditions,
also allows the quantitative initiation early in the process
necessary for synthesizing polymers with special architecture and
functionality. CRP processes may not eliminate the chain-breaking
reactions; however, the fraction of chain-breaking reactions is
significantly reduced from conventional polymerization processes
and may comprise only 1-10% of all chains.
[0006] The initiator for a CRP can be a small molecule with
additional functionality, an oligo/polymer chain with dispersed or
terminal initiating functionality, or initiating functionality can
be attached to any physical surface including particles of any
composition or size and to flat surfaces. In this manner,
functional particles or functional surfaces can be prepared. When
only partial coverage of a surface is employed, an array of
functional segments on a surface can be formed. Such a material
would find utility of many bio-applications where the functional
areas could be responsive to different peptides.
[0007] ATRP is one of the most successful controlled/"living"
radical processes (also CRP) developed and has been thoroughly
described in a series of co-assigned U.S. patents and applications,
U.S. Pat. Nos. 5,763,548; 5,807,937; 5,789,487; 5,945,491;
6,111,022; 6,121,371; 6,124,411; 6,162,882; 6,407,187; 6,512,060;
6,538,091; 6,541,580; 6,624,262; 6,624,263 6,627,314; 6,759,49 and
6,790,9191 and U.S. patent application Ser. Nos. 09/359,359;
09/534,827; 10/034,908; 10/269,556; 10/289,545; 10/456,324;
10/625,890; 10/638,584; 10/684,137; 10/781,061; 10/788,995;
10/860,807, 10/992,249, and 60/611,853; all of which are herein
incorporated by reference, and has been discussed in numerous
publications by Matyjaszewski as co-author and reviewed in several
publications.
[0008] Polymers produced by ATRP methods often contain a terminal
halogen atom at the growing chain ends which can be efficiently
modified in various end-group transformations, replacing terminal
halogens with azides, amines, phosphines and other functionalities
via nucleophilic substitution or radical addition and radical
combination reactions. Indeed, this transformation chemistry can be
conducted on any halogen terminated polymer including polymers
prepared by cationic polymerization processes. However, ATRP is one
of the most attractive techniques for the synthesis of well-defined
end-functionalized polymers.
[0009] A group of high-yield chemical reactions were collectively
termed "click chemistry" reactions by Sharpless in a review of
several small molecule click chemistry reactions. [Kolb, H. C.;
Finn, M. G.; Sharpless, K. B. Angew. Chemie, Inter.I Ed. 2001, 40,
2004-2021] As used herein, a "click chemistry reaction" is a
reliable, high-yield, and selective reaction having a thermodynamic
driving force of greater than or equal to 20 kcal/mol. Click
chemistry reactions may be used for synthesis of molecules
comprising heteroatom links. One of the most frequently used click
chemistry reactions involves cycloaddition between azides and
alkynyl/alkynes to form the linkage comprising a substituted or
unsubstituted 1,2,3-triazole. Other click chemistry reactions are
chemoselective or regioselective, only occur between alkynyl and
azido functionalities with high yield of the 1,4-substituted
triazole. Another click chemistry reaction comprises nucleophilic
opening of strained ring systems. Typically, the ring opening of
strained ring systems comprises three membered ring systems, such
as epoxides, aziridines, cyclic sulfates, episulfonium ions, and
aziridinium ions. Preferably, epoxides and aziridines are used. The
click chemistry reaction is frequently performed in alcohol/water
mixtures or in the absence of solvents and the products can be
isolated in substantially quantitative yield. See Patton, Gregory
C., Development and Applications of Click Chemistry, Nov. 8,
2004.
[0010] Selective copper-based click chemistry was described by
Sharpless for the preparation of low molecular weight species;
[Demko, Z. P.; Sharpless, K. B. Angewandte Chemie, International
Edition 2002, 41, 2110-2113-2116] This reaction has been used by
Sharpless to conduct a polymerization using two appropriate low
molecular weight comonomers (a diazide and a dialkyne). [Punna, S.
et. al. Polym. Prep. Div. Polym. Chem. 2004, 45, 778-779.] The
resulting polymer had a broad MWD.
[0011] Tetrazoles, RCN.sub.4R', belong to a group of five-membered
heterocycles, the azoles. Those with no substituent at any of the
nitrogen atoms (RCN.sub.4H) are acidic, with plc values similar to
carboxylic acids RCO.sub.2H (pK.sub.a(tetrazole)=4.89,
pK.sub.a(5-methyltetrazole)=5.56, while
pK.sub.a(CH.sub.3CO.sub.2H)=4.75.sup.1), and are thus sometimes
referred to as "tetrazolic acids". Both classes of compounds
dissociated at physiological pH; however, tetrazoles and
tetrazolate anions are more lipophilic and more stable towards many
metabolytic reactions than the carboxylates. These features make
them important compounds for the design of drugs such as
antibiotics, antiviral, antiallergic, antihypertensive, and
radioprotective agents.
[0012] Some polytetrazoles have been prepared by the
(co)polymerization of various vinyltetrazole monomers or by the
post polymerization reaction of polyacrylonitrile with sodium azide
and ammonium chloride. However, such polymers were not prepared
using a controlled polymerization process and therefore do not have
the properties, such as composition, molecular weight distribution,
structure and topology of polymers prepared by controlled
polymerization processes.
[0013] Traditional procedures for the direct preparation of
tetrazoles in polymer backbones have recently been reviewed by
Kizhnyaev, [Kizhnyaev, V. N.; Vereshchagin, L. I. Russian Chemical
Reviews 2003, 72, 143-164] and described in; DE4211521 where the
copolymerization of 2H-tetrazole with vinyl monomers provided
homogeneous, reaction-processable polymers which are easily handled
during processing. The copolymers, e.g., graft copolymers prepared
from acrylonitrile, styrene, polybutadiene, and
5-phenyl-2-(4-vinylphenyl)-2H-tetrazole or
2-methyl-5-(4-vinylphenyl)-2H-tetrazole, are described as being
useful alone or in blends [e.g., with poly(butylene terephthalate)]
for the preparation of extruded articles showing high-impact
strength, high heat deformation temperature, and good chemical
resistance.
[0014] DE4211522 described that similar polymers, based on
vinyl-aromatic monomers, 2H-tetrazoles with vinyl:phenyl
substituents, and polydiene graft base are useful in preparation of
a polymer membrane, useful for ultrafiltration, dialysis etc.
[0015] DE4222953 described the preparation of post-modifiable
copolymers by emulsion copolymerization of styrene, acrylonitrile,
and 2-methyl-5-(4-vinylphenyl)-2H-tetrazole that are processable by
standard thermoplastic methods but could be modified by UV
irradiation to provide surface crosslinking for improved impact and
tensile strength. I.e., a low level of tetrazole functionality is
incorporated by copolymerization and used to initiate a grafting to
or a crosslinking reaction.
[0016] U.S. Pat. No. 3,397,186 indicated that triaminoguanidinium
salts of 5-vinyltetrazole polymers are prepared by copolymerization
and are useful as rocket fuel binders.
[0017] Stille described copolymerization of vinyl tetrazoles that
allowed thermal crosslinking of copolymers containing
dipolarophiles and the tetrazoles as nitrile imine dipol
precursors. [Stille, J. K.; Gotter, L. D. Kinet. Mech.
Polyreactions, Int, Symp. Macromol. Chem., Prepr. 1969, 1, 131-134;
Stille, J. K.; Chen, A. T. Macromolecules 1972, 5, 377-384.]
[0018] The homopolymer of 2-(4-ethenyl)phenyl-5-phenyl-2H-tetrazole
and its copolymers with styrene and acrylonitrile were prepared by
Darkow. [Darkow, R.; Hartmann, U.; Tomaschewski, G. Reactive &
Functional Polymers 1997, 32, 195-207.]The solution behavior of the
tetrazole-containing polymers is dependent on the H-bond
participation of tetrazole rings and by hydrophobic interactions
between monomer groups. [Annenkov, V. V.; Kruglova, V. Journal of
Polymer Science, Part A: Polymer Chemistry 1993, 31,
1903-1906.]
[0019] Polymers containing acrylonitrile functionality may be
converted to polymers containing tetrazole functionality. U.S. Pat.
No. 3,096,312 provides conditions for conversion of
polyacrylonitrile to poly(5-vinyltetrazole) with a molecular weight
distribution of greater than 2 by heating with NaN.sub.3 and
NH.sub.4Cl in HCONMe.sub.2 for 24 hours at 120-5 Degrees.
[0020] U.S. Pat. No. 3,350,374 describes the preparation of
copolymers of hydroxytetrazoles and hydrazide oximes. These
polymers were prepared by modification of another precursor
polymer. The polymers are prepared from poly(hydroxamic acids) by
treatment with SOCl2, giving poly(hydroxamyl chloride), which was
then treated with hydrazine, giving the poly(hydrazide oxime).
Treatment with NaNO2 and HCl gives a poly(azide oxime), which then
rearranges to poly(hydroxytetrazole). The products are used as ion
exchangers and explosives. The process is described as being less
dangerous than the polymerization of a vinyltetrazole, but again,
the initial polymers were not prepared by a controlled
polymerization process and are therefore unable to be tailored to
meet the requirements of property selective applications. In all
prior publications and discussions on tetrazole-containing
polymers, the copolymer had been prepared by standard
polymerization processes; therefore, no control over any molecular
parameter was possible.
[0021] Thus, there is a need for a method of preparing polymers,
such as polytetrazole (co)polymers with controlled functionality,
topology, and composition.
SUMMARY
[0022] The process of the present invention is directed toward
conducting highly selective, high yield post polymerization
reactions on polymers to prepare functionalized polymers. An
embodiment of the present invention comprises conducting click
chemistry reactions on polymers. Preferably, the polymers are
prepared by controlled polymerization processes. Therefore,
embodiments of the present invention comprise processes for the
preparation of polymers comprising conducting a click chemistry
reaction on a functional group attached to a polymer, wherein the
polymer has a molecular weight distribution of less than 2.0. The
functional polymers may be prepared by converting an attached
functional unit on the polymer thereby providing site specific
functional materials, site specific functional materials comprising
additional functionality, or chain extended functional
materials.
[0023] Embodiments of the process of the present invention also
include chain extensions reactions by directly linking polymer
chains or by using a linking compound. In addition, the linking
reactant involved in the click chemistry reaction with the
functional polymer may provide additional distributed functionality
to the final polymer, such as linkages that may interact with
bio-active species or molecules. The distributed functionality may
comprise degradable functionality, such as biodegradable or
photodegrable functionality.
[0024] Embodiments of the process of the present invention also
include reacting a terminal group on a first polymer with a
compound to form a polymer comprising groups capable of reacting in
a click chemistry reaction and conducting a click chemistry
reaction resulting in chain extending the functional polymers to
form a higher molecular weight polymer. Such embodiments of the
process of the present invention may also include reactions systems
comprising multiple click chemistry reactions involving different
reactive groups. Simultaneous multiple high yield chemistries may
be performed if one reaction does not interfere with any of the
other reactions, and may be used to prepare multi-segmented block
copolymers, including, but not limited to, linear block, comb,
graft, branched, bottlebrush, as well as other topologies, such as
ABC, ABCABC or ABCD block copolymers by selecting the end
functional groups on each precursor copolymer segment to allow only
coupling or chain extension with the desired next polymer
segment.
[0025] The click chemistry reactions of the present invention
include reactions with polymers comprising side chain functionality
capable of reacting in a click chemistry reaction. Such polymers
include polymers comprising blocks of acrylonitrile monomers or
derivatives of acrylonitrile monomers. Such embodiments may result
in the formation of linear polymers with distributed functionality.
When the click chemistry reaction is conducted between polymers
comprising side chain functionality capable of reacting in a click
chemistry reaction and polymers comprising corresponding terminal
functionality capable of reacting in the same click chemistry
reaction, the reaction may result in formation of graft copolymer.
Click chemistry may be useful also for the formation of block
copolymers when the polymers are attached to a polymer, particle or
a substrate.
BRIEF DESCRIPTION OF THE FIGURES
[0026] The features and advantages of the present invention may be
better understood by reference to the accompanying figures, in
which:
[0027] FIG. 1 is a graph of an NMR spectrum of copolymer formed
after tetrolization of a styrene acrylonitrile copolymer;
[0028] FIG. 2 is a graph of IR spectra, films from chloroform on a
NaCl plate, of poly(styrene-b-acrylonitrile) copolymer ("SAN") and
the product of its tetrazolation, showing the presence of a new
band at 1653 cm.sup.-1, as well as the broad band from 2800 to 2300
cm.sup.-1) corresponding to associated NH bonds;
[0029] FIG. 3 is a graph showing the conversion of the nitrile
groups in a SAN copolymer to tetrazole units, spectra were obtained
from films cast from acetone (SAN34 and TTRZL11) or DMF (PANlttrzl
and TTRZL10) onto KBr plates; and
[0030] FIG. 4 is a graph showing the evolution of the SEC traces
during step growth click coupling of (a)
.alpha.-alkyne-.omega.-azido-terminated polystyrene after its
isolation and mixing with CuBr in DMF.
DESCRIPTION OF EMBODIMENTS OF THE INVENTION
[0031] The process of the present invention is directed toward
conducting highly selective, high yield post polymerization
reactions on polymers to prepare functionalized polymers. An
embodiment of the present invention comprises conducting click
chemistry reactions on polymers prepared by a controlled
polymerization processes. Therefore, embodiments of the present
invention comprise processes for the preparation of polymers
comprising conducting a click chemistry reaction on a functional
group attached to a polymer, wherein the polymer has a molecular
weight distribution of less than 2.0. The functional polymers may
be prepared by converting an attached functional unit on the
polymer thereby providing site specific functional materials, site
specific functional materials comprising additional functionality,
or chain extended functional materials.
[0032] All click chemistry reactions discussed by Sharpless are
highly selective, high yield reactions that may be used for
post-polymerization functionalization and chain extension chemistry
as exemplified herein. Some further examples of reactions which are
known to proceed in highly selective, high yield, and should not
interfere one with another, or at least the products of these
reactions should not interfere with the reagents used for another
reaction, include, but are not limited to, a hydrosilation reaction
of H--Si and simple non-activated vinyl compounds, urethane
formation from alcohols and isocyanates, 2+3 cycloaddition of alkyl
azides and acetylenes, Menshutkin reaction of tertiary amines with
alkyl iodides or alkyl trifluoromethanesulfonates, Michael
additions e.g. the very efficient maleimide-thiol reaction, atom
transfer radical addition reactions between --SO2Cl and an olefin
(R.sup.1, R.sup.2--C.dbd.C--R.sup.3, R.sup.4), metathesis,
Staudinger reaction of phosphines with alkyl azides, oxidative
coupling of thiols, many of the procedures already used in
dendrimer synthesis, especially in a convergent approach, which
require high selectivity and rates. Therefore, attached
functionality may be chosen from acetylene bond, an azido-group, a
nitrile group, acetylenic, amino group, phosphino group. The click
chemistry reaction may result in the addition of a functional group
selected from amino, primary amino, hydroxyl, sulfonate,
benzotriazole, bromide, chloride, chloroformate, trimethylsilane,
phosphonium bromide or bio-responsive functional group including
polypeptides, proteins and nucleic acids to the polymer. Therefore,
an embodiment of the process of the present invention comprises
reacting a polymer comprising at least one nitrile group with an
azide to form a polymer comprising at least one tetrazole ring. The
azide may be a functionalized azide.
[0033] The advantages of performing click chemistry reaction on
polymers produced by a controlled polymerization process is that
the polymers with narrow molecular weight distribution and regular
topology may be linked together in unique ways, functionalized at
specific sites, or two ends of a polymer chain may be joined
together to form cyclic polymers having a narrow molecular weight
distribution. For example, block copolymers comprising monomers
that may not readily copolymerize may be prepared by preparing the
polymer segments separately, even by separate polymerization
processes, and subsequently functionalizing the segments with
functional capable of reacting in a click chemistry reaction. In
this way, block copolymers may be prepared including AB copolymers,
but also repeating (AB).sub.n, (ABC).sub.n and (ABCD).sub.n
copolymers and such repeating block copolymers where n is greater
than 1. Such block copolymers may be formed by the reaction
between, for example, polymers of the formula Y--P-Z, where Y and Z
are corresponding click chemistry reaction groups, and P may be a
homopolymer, a copolymer, a block copolymer, a gradient copolymer,
an alternating copolymer or any other polymeric topology.
Additionally, polymers of the formula Y--P--Y may be reacted with
linking compounds of the formula Z-R-Z, where the constituents are
as defined above. Further multiple click chemistry reactions may be
performed between polymers of the formula, such as, but not limited
to, Y.sup.1--P-Z.sup.2, Y.sup.2--P.sup.2-Z.sup.1, wherein Y.sup.1
and Z.sup.1 are corresponding click chemistry reaction groups and
Y.sup.2 and Z.sup.2 are corresponding click chemistry reaction
groups that will not react with either Y.sup.1 or Z.sup.1, hereby
polymers comprising repeating structures such as (AB).sub.n,
(ABC).sub.n, and (ABCD).sub.n may be produced.
[0034] The selection of the reaction chemistry for each linking
reaction should not interfere one with another. y.sup.1 would only
react with z.sup.1, and y.sup.2 would only react with z.sup.2, etc.
As noted above, the only requirement is that the functional groups
in each generation do not interfere in the earlier linking chemical
bond formation reactions. For example, one link could be formed by
a hydrosilation reaction (A=H--Si and A'=an olefin), another link
could be formed by an ATRA between --SO2Cl (B) and an olefin
(B'.dbd.R.sup.1, R.sup.2--C.dbd.C--R.sup.3, R.sup.4); or through
use of a 2+3 cycloaddition reaction between an acetylene and an
alkyl azide via "click chemistry".
[0035] A problem that may likely be encountered in such embodiments
may arise from the difficulty in finding a set of reactions which
conform to the above criteria. For example, if one decides to
employ a Michael reaction of electron-poor alkenes with primary or
secondary amines, the latter may compete with any alcohols selected
to participate in urethane formation. Similar interference will be
encountered for a reaction between amines, carboxylic acids and
Michael addition. Also, the very selective atom transfer radical
addition of sulfonyl halides to alkenes should be used in the
absence of amines or alcohols, etc. Nevertheless, these reactions
could be still used in a one-pot but two-step approach, when the
monomer utilizing amines as one functional group in the forming
linking chemistry could be added only after the alcohol is totally
consumed or sulfonyl halide reacted with alkenes.
[0036] For example, in one embodiment, a process for the
preparation of regular linear multi-segmented block copolymers may
comprise reacting polymers with selected terminal functionality
such as A'-P.sub.1--B, B'-P.sub.2--C, C'-P.sub.3-D and Ds-P.sub.4-A
can use the selective linking chemistry to make a linear
At(P.sub.1)B:13'(P.sub.2)C:C'(P.sub.3)D:D'(P.sub.4).sub.n
multiblock segmented copolymer of controlled sequences of polymer
segments, optionally with pre-selected chain end functionality.
[0037] The linking chemistry can be conducted in solution or in
bulk. In the case of linking higher molecular weight polymer
precursors, the "one pot" could be an extruder, preferentially a
twin screw extruder with devolatization capabilities.
[0038] A further embodiment of the process of the present invention
comprises reacting a first polymer comprising at least one nitrile
group with an azide comprises reacting the first polymer with
sodium azide and zinc chloride and wherein the molar ratio of
sodium azide to nitrile groups and the molar ratio of zinc chloride
to nitrile groups are both individually greater than 1.5.
Embodiments of the processes of the present invention may
preferably include reactions with polymers produced by a controlled
polymerization processes such that the polymers have a molecular
weight distribution of less than 2.0.
[0039] A particularly useful linking reaction is the
copper-(I)-catalyzed 1,2,3-triazole formation from azides and
polymers comprising terminal acetylenes, due to its high degree of
dependability, complete specificity, and the bio-compatibility of
the reactants. The click chemistry reactions may be used for
transformation of functional groups attached to monomers,
attachment of additional functional groups, clicking of telechelic
groups on polymers for preparation of block copolymers, conducting
linking reactions for formation of linear polymers with distributed
functionality, or graft copolymers by "clicking to" a polymer,
particle or substrate. The polymers of the present invention may
thereby by supported on at least one of an inorganic support and an
organic support, ion exchange resin, a silica particle, and a
poly(styrene) particle.
[0040] For chain extensions reactions, for example, the reactant
involved in the click chemistry reaction with the polymer may
provide additional functionality to the new polymer, such as
linkages that may interact with bio-active species or molecules.
Embodiments of the process of the present invention also includes
reacting a terminal group on a first polymer with a compound to
form a polymer comprising groups capable of reacting in a click
chemistry reaction and conducting a click chemistry reaction
resulting in chain extending the functional polymers to form a
higher molecular weight polymer. Such embodiments of the process of
the present invention may also include reactions systems comprising
multiple click chemistry reactions involving different reactive
groups. Multiple high yield chemistries where one reaction does not
interfere with any of the other reactions, may be used to prepare
multi-segmented block copolymers, including, but not limited to,
linear block, comb, graft, branched, bottlebrush, as well as other
topologies, such as ABC or ABCD block copolymers by selecting the
end functional groups on each precursor copolymer segment to allow
only coupling or chain extension with the desired next polymer
segment.
[0041] Embodiments of the process of the present invention also
comprise linking polymers by reacting a linking compound by a click
chemistry reaction with two or more polymers, wherein the polymers
comprise corresponding click chemistry functionality. Such a chain
extension reaction results in polymer segments with distributed
linking groups. In some applications it may be preferable for the
linkages to be distributed regularly along the polymer backbone or
side chains. The distributed functionality may comprise degradable
functionality.
[0042] The click chemistry reactions include reactions with
polymers comprising side chain functionality capable of reacting in
a click chemistry reaction. Such polymers include polymers
comprising blocks of acrylonitrile monomers or derivatives of
acrylonitrile monomers. Such embodiments may result in the
formation of linear polymers with distributed functionality. When
the click chemistry reaction is conducted between polymers
comprising side chain functionality capable of reacting in a click
chemistry reaction and polymers comprising corresponding terminal
functionality capable of reacting in the same click chemistry
reaction, the reaction may result in formation of graft copolymer.
Click chemistry may be useful also for the formation of block
copolymers when the first polymers are attached to a polymer,
particle or a substrate. Polymerizations of polymers attached to a
polymer backbone, a particle, or a substrate may result in a higher
degree of termination reaction due to the proximity of the active
propagating chain ends, therefore, click chemistry reactions
wherein the adjacent polymers are not capable of reacting with each
other, would result in a more efficient means extending such
tethered polymers.
[0043] Further embodiments comprise functionalizing each terminal
end of a polymer with corresponding click chemistry reaction
functionality and reacting one end of the chain with the other in a
ring closing reaction to form a macrocyclic polymer. Embodiments of
the present invention also include functionalized polymers, such as
a polymer comprising 5-vinyltetrazole monomer units and having a
molecular weight distribution less than 2.0. The polymer may be one
of a star block copolymer, a linear polymer, a branched polymer, a
hyperbranched polymer, a dendritic polymer, a bottle-brush
copolymer and a crosslinked structure, such as a block copolymer
comprising a block of 5-vinyltetrazole monomer units. Multiblock
copolymers may comprise at least two blocks comprising
5-vinyltetrazole monomer units. Such a block copolymer may further
be capable of selective separation of closely related chemical
species such as ions, proteins or nucleic acids via ionic bonding
or complex formation.
[0044] Control over the distribution of the tetrazole functionality
can improve the performance of the material in many applications,
such as adding tetrazole functionality to a solid support, for
example, an organic based support, such as a crosslinked
polystyrene resin, or an inorganic support, such as SiO.sub.2.
[0045] The Examples demonstrate a process for the initial
preparation of homopolymers and block copolymers comprising a
polyacrylonitrile segment or a styrene/acrylonitrile copolymer
segment. The polyacrylonitrile block or statistical
styrene/acrylonitrile copolymer block may be directly prepared as a
bulk or solution processable material, may be directly grafted to a
substrate, or may be attached to the substrate via a hydrophilic or
hydrophobic spacer. Any material in a contacting solution may
freely interact with the first functionality as well as with the
tetrazole functionality. For many applications macrobeads allow
easier separation from the reactants/products than nanocolloids and
in such situations spacers can assist is ensuring good contact
between the functional material and the desired reactant. By
control over spacer length, composition, and distribution of the
attached tetrazole functionality one can modify the distribution of
the attached tetrazole functionality in the contacting medium and
allow close approach of a reactant, such as DNA or a protein to the
attached tetrazole functionality thereby promoting controlled DNA
synthesis in a readily separable solid/liquid reaction medium. In
addition, such materials may be separated using other methods. For
example, the material comprises the tetrazole functionality may
exhibit a lower solution critical temperature (LCST) thereby
allowing a homogeneous solution reaction between the tetrazole and
the contacting reactant at a first temperature while allowing
solid/liquid separation to be conducted at a lower second
temperature (for example if an additional block comprises at least
one of dimethylacrylamide, butyl acrylate, dimethylaminoethyl
methacrylate, diethyl acrylamide, and NIPAM).
[0046] Another route to preparation of a readily separable material
comprising tetrazole functionality tetrazole functionality would be
to prepare block copolymers with selectively separable segments,
such as by the preparation of copolymers with a short
polyacrylonitrile segment and a polyethylene glycol segment such a
block copolymer would allow a reaction to be conducted in one
medium then the tetrazole functional material could be removed by
extraction with a solvent for the other polymer segment. An example
of utility for such a material would be to use the azole
functionality as a ligand for a transition metal and an attached
stimuli-responsive or solvent specific polymer segment as a means
to remove the catalyst complex from the reaction medium.
[0047] The synthetic freedom that allows one to target specific
applications is further exemplified by segmented materials that are
suitable for selective separation which can comprise segments with
dimethylacrylamide/butyl acrylate (DMAA/BA), with
dimethylaminoethyl methacrylate (DMAEMA) and with diethyl
acrylamide (DEAA), or with NIPAM which can be prepared by RAFT.
[0048] A further process that would assist in the preparation and
purification of bio-responsive products would be to attach the
tetrazole functionality to a support with a cleavable functional
group and once the sequence of DNA had formed the polymer could be
selectively cleaved from the support prior to deprotection.
[0049] A further use for block copolymers with tetrazole
functionality would be the formation of coatings where the first of
post-polymerization functionalized (co)polymer can phase separate
into discrete nano-domains such as formation of free standing films
wherein the isolated tetrazole segments could form iron (II)
complexes that could undergo separate spin-spin transitions under
stimulation thereby storing information.
[0050] Another use for polymers, particularly dendritic or
hyperbranched polymers with attached tetrazole functionality would
be to use such a system for solid explosives. Such a material with
high concentration of tetrazole functionality could be prepared by
synthesis or a normal or hyperbranched polyacrylonitrile-Br polymer
followed by conversion of the acrylonitrile functionality to
tetrazole functionality and the bromo-functionality to azide.
[0051] Block copolymers and statistical copolymers of styrene and
acrylonitrile were synthesized, halogen exchange was used to
prepare well defined polyacrylonitrile blocks from a polystyrene
macroinitiator. The nitrile groups were modified to tetrazole units
using the chemistry shown in scheme 1.
##STR00001##
[0052] The ionomers with random or blocky structures containing
amino and tetrazole groups were studied for aggregation in
solution, complex-formation, and morphology. The
tetrazole-containing polymers will be tested as materials for the
synthesis of DNA.
[0053] Other polyacrylonitrile block copolymers that were converted
to polytetrazole block copolymers were linear block copolymers with
polyethylene oxide and star block copolymers with a poly(butyl
acrylate) core, thereby exemplifying the broad scope of
copolymerizable monomers.
[0054] The nitrile groups of styrene-acrylonitrile based copolymers
were successfully transformed to tetrazole units by the reaction
with zinc chloride and sodium azide in DMF. The ionomer initially
obtained, using published procedures for the preparation of low
molecular weight species or indeed as recommended below with an
even greater excess of sodium azide, up to 2:1 ratio, still
contained acrylonitrile units (see the NMR spectrum in FIG. 1), but
had drastically different properties from the starting material,
for example; it dissolved in methanol and swelled in water.
Increasing the molar ratio of sodium azide to nitrile units above
the ratio of 1:1.3 provided (co)polymers with complete conversion
of the nitrile unit to tetrazole.
[0055] A second series of Examples describes a combination of high
yield chemistry and ATRP leading to the preparation site specific
and homo-functional polymers. Telechelic polymers with different
chain end functionality can be used for inter- and intra-molecular
click coupling reactions. Embodiments of the present invention
include a method of preparing molecular brushes with block
copolymer architecture in both the backbone and direction of the
tethered graft block copolymers. These materials could be examples
of a unimolecular cylindrical Janus micelle, and the aggregation
behavior in solution and bulk phases is expected to be interesting.
With the exception of relatively short blocks being added to
molecular brushes via grafting through of macromonomers, the
synthesis of multi-segmented block brush copolymers has remained
elusive and the chemistry described herein provides an expedient
approach to synthesize such molecules.
[0056] The use of high yield post-polymerization chemistry in
combination with polymers prepared by controlled polymerization
procedures including ionic polymerization processes and CRP should
allow for the preparation of well-defined complex structures such
as molecular brushes with blocky structure or "heterogeneous"
brushes with random incorporation of two different side chains
(Scheme 2). For example, monomers with an acetylene bond
incorporated into a polymer by a CRP may be converted to an
initiating group for a grafting from reaction using
azido-group-containing initiator or vice versa. This chemistry can
also be used to attach a second desired functionality, such as
halogen, primary amine, phosphorous group, silane or siloxane or
functionality that can bind to bio-responsive materials at any site
along the polymer chain.
##STR00002##
[0057] The utility of this approach to functional polymers is
exemplified by the preparation of homopolymers of 3-azidopropyl
methacrylate by ATRP and by RAFT, followed by attachment of a
hydroxyl group at each functional monomer unit along the backbone
by a click chemistry reaction with propargyl alcohol.
[0058] There is a multiplicity of azido-monomers that can be
synthesized and used in the preparation of a (co)polymer and this
is further exemplified below by synthesis and polymerization of
4-vinylbenzyl azide. Similarily, most radically copolymerizable
monomer can be modified to include substituent that can participate
in a post-polymerization reaction. This, therefore, provides
complete synthetic freedom for the preparation of the first
functional copolymer since comonomers with appropriate reactivity
can be selected to form random, statistical or gradient copolymers
or segment of a linear copolymer, a block copolymer, a star
copolymer, a graft copolymer or a copolymer with more complex
topology.
[0059] Further there is a multiplicity of propargyl derivatives
available commercially. Propagyl derivatives may be used in a
similar manner to attach a third functionality to an azido-group at
any specific site on a polymer or particle. For example, propargyl
amine can be used to attach primary amine functionality to each
monomer site since monomers containing primary amine groups may not
be readily polymerized by CRP processes. Propargyl benzene
sulfonate may be used to attach a sulfonate group to a monomer,
chain end, or segment comprising azido units. Other propagyl
derivatives include functionality that can be introduced after a
visit to Aldrich includes: benzotriazole, bromide, chloride,
chloroformate, trimethylsilane, or phosphonium bromide
functionality. Indeed, the ready availability of propargyl bromide
allows the preparation of other propargyl derivatives since allylic
nucleophilic substitution and also "propargylic" substitution are
particularly easy. This indicates the ease of attaching any desired
functionality to a preformed functional polymer by utilizing the
chemistry discussed herein. As noted above in scheme 2, the added
functionality can further comprise an initiator for a CRP thereby
allowing the formation of heterograft brush copolymers or double
graft brush copolymers.
[0060] Therefore, embodiments of the present invention include
reacting propargyl compounds and derivative such as, but not
limited to, the ones defined as
##STR00003##
R.sup.1, R.sup.2, and R.sup.3 may independently be H, halogen, Cl,
Br, OH, NH3, alkyl, aryl, alkoxy, --OR.sup.7, alkyl amine,
--NHR.sup.7, --N(R.sup.7).sub.2, substituted or unsubstituted
phenyl, phenyl sulfonate, benzotriazole, haloformate,
trialkylsilane, phosphonium halide, or --SR.sup.7; wherein R.sup.7
is independently selected from one of an alkyl group or an aryl
group
[0061] The attached functionality can be the final desired
functionality in the material or can be employed in subsequent
reactions to attach additional groups or interact with responsive
materials including bio-responsive materials, such as proteins with
chain end functionality.
[0062] The triazole products may be more than just passive linkers,
for example, triazoles readily associate with biological targets,
through hydrogen bonding and dipole interactions and as such may
preferentially be placed near the shell of the final structure, or
near an incorporated oligo/polymeric segment, to allow the greater
free volume of the selected environment to accommodate an added
agent.
[0063] The high yield post-polymerization chemistry can also be
used in chain extension chemistry. This is exemplified below by
chain extension of both homo-telechelic polystyrene and
hetero-telechelic polystyrene, but can be applied to polymers of
any composition. Indeed the chemistry can be used to couple block
copolymers together to form multi-block segmented copolymers. A
tele-functional AB block copolymer with attached click chemistry
functionality would form an (AB).sub.n segmented copolymer and an
ABC block copolymer would similarly form a regular (ABC).sub.n
multiblock copolymer. Multi-segmented linear block copolymers with
well defined segments have not been readily prepared before.
[0064] Further the disclosed process could be a preferential route
for the synthesis of ABC block copolymers of various topology
including stars and graft copolymers where the A block, B block and
C block are not readily copolymerized in sequence. Each segment may
be prepared individually and then the final copolymer assembled in
either a single step or a dual step clicking together reaction
using single or multiple click chemistries to attain the final
polymer structure.
[0065] Further as disclosed below in the examples the process of
the present invention additionally provides a route for the high
yield preparation of macro-cyclic copolymers, a species of polymer
hitherto difficult to prepare. The % cyclization from a given
telechelic copolymer may be controlled by selection of the solvent
for the first linear copolymer. A poor solvent is preferred in
order to modify the solution morphology of the copolymer to a
preferred globular structure. The solvating power of a good solvent
for the linear copolymer can be modified by addition of a miscible
poor solvent or non-solvent to attain the desired collapsed
structure. The result is that the predominant product from a click
coupling reaction can be a cyclic polymer.
EXAMPLES
Preparation of Copolymers of Acrylonitrile with Controlled
Molecular Weight, Topology and Functionality and their Chemical
Modification to Polytetrazole Containing Materials
[0066] The 1,3-dipolar cycloaddition of azide to organic nitriles
in the presence of a protic or Lewis acid leading to 5-substituted
tetrazoles, as shown in Scheme 1, is an example of "click
chemistry" or a high yield post polymerization reaction. The
tetrazole synthesis is usually carried out at high temperatures
(above 100.degree. C.) in polar solvents such as DMF, DMSO,
butanol, or in aqueous media. Hydrazoic acid can be directly used
to form the azole ring but since it is a highly toxic and explosive
substance, other acids are preferably employed, in conjunction with
a source of azide. Examples of acidic compounds include
trifluoroacetic acid, aluminum or tin compounds, and ammonium
salts. Zinc halides are quite efficient and the chloride was used
in the present work
Example 1
Conversion of the Nitrile Groups in a SAN Copolymer to Tetrazole
Unit
[0067] 2.79 g (0.3 mmol, corresponding to approximately 0.012 mol
of nitrile groups) of a styrene/acrylonitrile copolymer (SAN28
M.sub.n=9260 g/mol, PDI=1.14) was dissolved in 10 ml of DMF. 1.56 g
(0.024 mol) of sodium azide and 3.27 g (0.024 mol) of zinc chloride
were then added and the mixture was stirred at 100.degree. C. for
24 h. After about 4 h, the salts had almost completely dissolved. A
mixture of 200 ml of water and 15 ml of concentrated hydrochloric
acid was separately prepared. 2 ml of this mixture was added to the
reaction mixture (the latter had been cooled down to 60.degree.
C.), and the obtained suspension of polymer was stirred at
60.degree. C. for 2 h. The polymer was then precipitated in the
same dilute hydrochloric acid. The resulting suspension was stirred
at room temperature overnight. The filtered polymer was washed with
water and methanol on the filter. It was then dissolved in DMF (20
ml), and the turbid mixture was poured in the same amount of dilute
HCl as before. The polymer was filtered, washed with water and
methanol, and dried. These purification steps are necessary to
remove the inorganic salts (especially the zinc salts which
hydrolyze forming products that are insoluble in water but soluble
in HCl). Finally, the polymer was dissolved in 15 ml of acetone,
filtered and precipitated in 200 ml of water. After cooling the
suspension in a refrigerator, the suspension was filtered and the
polymer was dried and analyzed by IR spectroscopy (film from
chloroform on a NaCl plate). All characteristic peaks of
poly(5-vinyltetrazole) were observed, see FIG. 2. It should be
noted that the band of the nitrile group did not completely
disappear in the prepared polytetrazole.
[0068] These terazolation reactions on SAN copolymers yielded
methanol-soluble polymers with high tetrazole content. The
copolymer was characterized by .sup.13C NMR spectroscopy (FIG. 1).
The peak at 157 ppm is due to the carbon atom from the tetrazole
ring, and the peak a 120 ppm is due to nitrile carbon atoms. The
tertiary carbon atom of polystyrene resonates at 145-148 ppm. The
carbon atoms of the macrochain of poly(5-vinyltetrazole) absorb at
37-38 ppm (the peaks of these from PAN are situated at 27-28 ppm
and from polystyrene--at 40-48 ppm). Therefore, the degree of
tetrazolation is approximately 70%.
Example 2
Synthesis of Block (Co)Polymers Containing Tetrazole Groups by
ATRP
[0069] Two different block copolymers of styrene and acrylonitrile
were prepared. Sty.sub.190AN.sub.38 and Sty.sub.190AN.sub.10. These
polymers were then converted to tetrazole-containing copolymer by
the reaction with excess molar levels of sodium azide in the
presence of zinc chloride.
Example 2a
Preparation of Diblock Copolymers of Styrene and Acrylonitrile
using Halogen Exchange to Prepare Narrow Molecular Weight
Polyacrylonitrile Blocks
[0070] 6.93 g of a pStyBr macroinitiator (Mn=19800 g/mol) was
dissolved in a mixture of 14 ml of DMF and 10.5 ml of AN added. The
catalyst complex for the ATRP consisted of 0.035 g CuCl and 0.109 g
bpy. The polymerizations were performed at 80.degree. C. The
results are presented in Table 1.
TABLE-US-00001 TABLE 1 Preparation of poly(styene-b-acrylonitrile)
copolymers Mn, g/mol Time of pzn, Conv (GPC, conv., and NMR) Entry
min (GC) [DP of AN block by NMR] PDI Sty-b-AN3 90 0.140 21700,
21200 [36] 1.16 Sty-b-AN4 25 0.052 20500, 20400 [10] 1.13
[0071] The two copolymers with pAN blocks of DP=10 and 38 were used
for the preparation of the corresponding block-tetrazoles and
block-amines copolymers. The micellular association of these block
copolymers in solution will be studied, as well as using them as a
template for absorption of metal ions.
Example 2b
Peparation of Tetrazole Containing Block Copolymers from Diblock
Copolymers of Sty and AN (Sty-b-AN3 [DP of AN=36] and Sty-b-AN4 [DP
of AN=10])
[0072] The block copolymers of styrene and acrylonitrile prepared
above, (Styl.sub.90AN.sub.38 and Sty.sub.190AN.sub.10) were reacted
with 4 equivalents of the salts and the reaction was complete in
approximately 50 hours.
Example 2b1
[0073] 2.5 g (4 mmol of nitrile groups) of the polymer Sty-b-AN3
was dissolved in 10 ml of DMF. 1.04 g (16 mmol) of sodium azide and
2.18 g (16 mmol) of anhydrous zinc chloride were added and the
mixture was heated (using a reflux condenser) to 120.degree. C. for
50 h. Then it was cooled down to 60.degree. C. and 2 ml of HCl
(1:10 by volume in water) was added. The mixture was stirred for 2
hours and the polymer was precipitated in 200 ml (1:10) HCl. Based
on IR spectral analysis, almost complete conversion of nitrile
groups to tetrazole units took place.
Example 2b2
[0074] 2.5 g (1.23 mmol of nitrile groups) of the polymer Sty-b-AN4
was dissolved in 10 ml of DMF. 0.32 g (4.9 mmol) of sodium azide
and 0.67 g (4.9 mmol) of anhydrous zinc chloride were added and the
mixture was heated (using a reflux condenser) to 120.degree. C. for
50 h. Then it was cooled down to 60.degree. C. and 2 ml of HCl
(1:10 by volume in water) was added. The mixture was stirred for 2
hours and the polymer was precipitated in 200 ml (1:10) HCl. Based
on IR spectral analysis, almost complete conversion of nitrile
groups to tetrazole units took place.
[0075] A segmented block copolymer with aligned tetrazole
functionality of degree of polymerization close to ten is expected
to provide a molecularly isolated complex with Fe(II) complexes
that will display spin-spin transitions under stimulation thereby
storing information at the molecular level. The presence of a
polystyrene block will allow the formation of coherent coatings or
free standing films. Other segments can also be employed.
Example 3
Synthesis of AN-BA Diblock Copolymer
[0076] A pBA-based macroinitiator was prepared by ATRP of BA (50
ml, with 2 ml of diphenyl ether added as internal GC standard) in
the presence of CuBr (0.0784 g)/PMDETA (112 .mu.l) complex,
initiated by MBP (64 .mu.l). The polymerization was carried out at
70.degree. C. for 23.5 h (conversion by GC was 62.7%). The product
was dissolved in ca. 300 ml of THF and the copper complexes were
removed by passing the solution through a column filled with
neutral alumina. The solvent was then evaporated providing a
polymer with Mn=68.7 kg/mol, PDI=1.09 (pSty standards).
[0077] 17.66 g of the macroinitiator was dissolved in a mixture of
50 ml of AN and 20 ml of DMF. The chain-extension was catalyzed by
CuCl/bpy. The reaction was carried out at 70.degree. C. for 21.5 h.
The polymer was precipitated in methanol, and analyzed by GPC:
Mn=92.4 kg/mol, PDI=1.18 (pSty standards).
[0078] This result proves the earlier observations that DMF is the
solvent of choice for the preparation of acrylonitrile copolymers
of high molecular weight. This copolymer had a cylindrical
morphology.
Example 4
Tethered Tetrazole (Co)polymers
[0079] A polyacrylonitrile homopolymer and a styrene/acrylonitrile
copolymer both attached to silica particles and crosslinked
polystyrene particles were also converted to tetrazoles. Based on
IR spectral analysis, no unreacted nitrile groups were left in the
samples.
Example 4a
[0080] The general procedure for conversion of nitrile
functionality in these Examples was as follows. The measured amount
of the tethered (co)polymer was dissolved in DMF, and NaN.sub.3 and
anhydrous ZnCl.sub.2 (4 equivalents vs. CN) were added. The mixture
was stirred at 120.degree. C. for 50 h, then cooled to 60.degree.
C. and a solution of HCl (1:10 in water) was added. The reaction
mixture was stirred at this temperature for 3-5 h, and the product
was precipitated in large excess of the same HCl solution. The
polymer was stirred with the HCl overnight at room temperature,
filtered, washed on the filter with the same HCl solution and then
with water and dried. Experimental details are summarized in Table
2.
TABLE-US-00002 TABLE 2 Tetrazolation reactions Experiment Polymer
Reagents HCl (1:10) Properties ttrzl9 SAN-SiO.sub.2 (L.B.) - 1.4 g
1.56 g NaN.sub.3 2 mL; 5 h at -- (0.006 mol CN) in 10 mL and 3.27 g
60.degree. C. DMF ZnCl.sub.2 (0.024 mol) ttrzl10 PAN1ttrzl (Mn
(GPC) = 5.2 g NaN.sub.3 15 mL; 3 h at Sol. DMF (heating), 39540
g/mol, PDI = and 10.9 g 60.degree. C. (brown aq. NaOH; 1.08), 1.06
g (0.02 mol ZnCl.sub.2 solution insol. H.sub.2O, MeOH, CN) in 20 mL
DMF (0.08 mol) forms) acetone ttrzl11 SAN34 (Mn = 8460 g/mol, 3.12
g NaN.sub.3 10 mL; 4 h at Sol. MeOH, aq. PDI = 1.08), 2.79 g and
6.54 g 60.degree. C. (in ca. NaOH, acetone (0.012 mol CN) in 20 mL
ZnCl.sub.2 1 h, solution DMF (0.048 mol) forms)
[0081] The IR spectra of the starting nitrile-containing polymers
and the tetrazoles prepared therefrom are shown in FIG. 3. As can
be seen from the spectra, it appears the nitrile groups were
completely converted to tetrazole functionality.
Example 4b
[0082] Polystyrene particles functionalized with ATRP initiating
groups were purchased from Aldrich and were grafted from and
functionalized as described above. Tetrazole encapsulated
polystyrene particles could be used as a substrate in a gel packed
column.
[0083] In this initial example of post-polymerization
functionalization well-defined homo- and copolymers (both random
and block, including supported polymers on polystyrene or silica
particles) of AN were synthesized using copper-mediated ATRP. In
order to obtain a low-polydispersity Sty-AN block copolymer, the
polyAN block should be synthesized first and the polyANBr
macroinitiator chain-extended with Sty. All
nitrile-group-containing polymeric materials were modified to the
corresponding tetrazoles using the reaction with sodium azide and
zinc chloride in DMF. The optimum results were achieved when the
reaction was carried out at 120.degree. C. for 50 h using a ratio
of the reagents NaN.sub.3:ZnCl.sub.2:RCN equal to 4:4:1. The
tetrazole-based polyacids prepared by this "click chemistry"
reaction were characterized by IR and .sup.13C NMR spectroscopy.
The 5VT homo and random copolymers had markedly better solubilities
in protic solvents than the starting materials being soluble in
alkaline aqueous solutions.
[0084] Click chemistry may be used to convert --C.ident.N groups on
polymers with degrees of polymerization of less than 2.0 to
tetrazole groups. Hybrid copolymers comprising a copolymer tethered
to a solid may also be modified thereby preparing functional micro-
or macro-particles.
Example 5
Examples of Other High Yield Post-Polymerization Functionalization
Chemistry
[0085] The approach shown above in Scheme 2 is exemplified by
synthesis and use of an azido-group-containing monomer
(3-azidopropyl methacrylate) and acetylene-group-containing
initiator (propargyl 2-bromoisobutyrate) and their incorporation
into polymers of controlled structure.
Example 5a
Synthesis of 3-azidopropanol
[0086] Several conditions were tested for the conversion of
3-halopropanols to 3-azidopropanol (neat liquids vs. solutions,
addition of phase transfer catalyst, various temperatures) and the
method presented here was the best (all others led to incomplete
conversion). It produced very clean alcohol, which can be converted
to the corresponding methacrylate.
[0087] 30 mL of 3-chloropropanol (33.93 g, 0.358 mol) were added to
a mixture of 40 mL of water, 47 g (twofold excess to the alcohol)
of sodium azide and 1 g of tetrabutylammonium hydrogensulfate. The
mixture was stirred at 80.degree. C. for 24 hours and then at room
temperature overnight (13-14 h). The product was extracted with
three portions (80-90 mL each) of ether, the combined ether
solutions were dried over sodium sulfate and the solvent was
removed on rotary evaporator. Thus 35.5 g of crude product was
obtained. The 3-azidopropanol was distilled under vacuum. Yield:
30.8 g (0.305 mol, 85%). .sup.1H NMR in chloroform (5, ppm): 3.76
(t, 2H, CH.sub.2O), 3.46 (t, 2H, CH.sub.2N.sub.3), and 1.84 (ft,
2H, CCH.sub.2C). No unreacted 3-chloropropanol was seen by NMR (its
peaks in CDCl.sub.3 are observed at 3.80 (t, 2H, CH.sub.2O), 3.68
(t, 2H, CH.sub.2Cl) and 2.01 (ft, 2H, CCH.sub.2C) ppm).
Example 5b
Synthesis of 3-azidopropyl methacrylate
[0088] 29 mL (0.3 mol) of methacryloyl chloride was added to a
mixture of 100 mL methylene chloride and 50 mL of pyridine (both
solvents had been dried over sodium sulfate overnight). The
suspension was cooled in an ice-water bath and 18.6 mL (0.2 mol) of
3-azidopropanol was added over a period of 10 minutes. A clear
solution was formed, which was kept in the cooling bath for another
1 hour and then at room temperature for 24 h. 50 mL of methylene
chloride were then added, and the mixture was extracted with a
solution of 50 mL HCl in 300 mL water followed by four
200-mililiter portions of water (NaCl had to be added to break the
stable emulsion). The methylene chloride layer was dried over
sodium sulfate (5 grams of sodium carbonate were added to react
with the excess of methacrylic acid potentially present), and the
solvent was removed under vacuum. The obtained liquid was distilled
under reduced pressure (0.1 g of hydroquinone was added to prevent
polymerization). The yield was 8.55 g (25%). The procedure needs to
be optimized, but the monomer obtained by this procedure was very
pure (NMR) and was used to study polymerization reactions.
Example 5c
ATRP of 3-azidopropyl methacrylate (AzPrMA)
[0089] The ratio of reagents were AzPrMA--2 mL (2.18 g, 0.0129
mol); acetone--2 mL, Ph.sub.2O--0.15 mL; CuBr--0.0093 g (0.0645
mmol, 1/200 vs. monomer); Bpy--0.00202 g
[0090] EBiB--9.5 .mu.L (1/200 vs. monomer); reaction temperature
50.degree. C. The mixture of monomer and solvents was degassed by 5
freeze-pump-thaw cycles, and the complex components were added to
the frozen mixture. The tube was closed and back-filled with
nitrogen. After dissolving the complex and heating the reaction
mixture, EBiB was injected. The results are presented below.
TABLE-US-00003 Sample Time, min Conv. (GC) Mn, g/mol* PDI* 1 65
0.171 6130 1.32 2 135 0.230 8090 1.36 3 210 0.290 9010 1.38 4 330
0.337 10580 1.42 5 480 0.431 12320 1.44 *Using polyMMA
calibration
Example 5d
3-azidopropyl Methacrylate Polymerized using RAFT Conditions
[0091] ([APMA]:[CDB]:[AIBN]=203:1:0.2, T=60.degree. C.).
[0092] The kinetics, MW vs. conversion, MWDs, and other data
indicated a well controlled polymerization. While usually RAFT
polymerizations of methacrylates are relatively fast with linear
pseudo first-order kinetics, there was a slight inhibition period
observed during this polymerization nevertheless a DP>100 is
attainable, and this could be sufficient for composing a portion of
a block copolymer brush.
Example 5e
Click Chemistry of poly(3-azidopropyl Methacrylate) and Propargyl
Alcohol
[0093] The final polymer from the previous experiment, (5c), (0.09
g, 0.53 mmol of azide groups) and 31 .mu.L (0.53 mmol) of propargyl
alcohol were dissolved in 1 mL of deuterated DMF. Nitrogen was
bubbled through the solution for 15 min. In a NMR tube, 0.0076 g
(0.053 mmol) of CuBr was put and the air in the tube was replaced
with nitrogen. 0.85 mL of the above solution was injected and the
tube was kept at 27.degree. C. The CuBr quickly dissolved forming a
yellow solution. After 5 hours, the NMR spectrum clearly indicated
the formation of the triazole (peaks appeared at 8.15 ppm,
corresponding to CH from the triazole ring, and at 5.40 ppm,
corresponding probably to CH.sub.2O connected to the aromatic ring.
The spectrum did not change anymore even after 25 hours, indicating
that the reaction was complete. This preliminary result indicates
that click chemistry reaction can be successfully carried out in
non-aqueous solvent, and is quite fast (often authors report
reaction times of 20 hours or longer). In addition, the Cu.sup.I
source does not require a ligand (perhaps the solvent serves as
such), which is useful for the attachment of propargyl
2-bromoisobutyrate to the azide monomer (which, in the presence of
a ligand is more likely to react with the CuX forming radicals). In
this way ATRP initiating sites were attached to the first polymer
backbone for a grafting from reaction.
Example 5f
Preparation of 4-vinylbenzyl Azide
[0094] Freshly distilled 4-vinylbenzyl chloride (4VBC) was reacted
with NaN.sub.3 (25 wt % in water) using the conditions we generally
employ to modify the halogen containing end groups obtained by ATRP
to azide groups (Scheme 3).
##STR00004##
[0095] This approach was successful with nearly none of the
starting product being observed in the .sup.1H NMR spectrum (d of
4VBC should be at 4.6 ppm) after 24 h at room temperature.
[0096] RAFT polymerization of 4-vinylbenzyl azide was conducted
with cumyl dithiobenzoate (CDB) and AIBN
(([4VBAz]:[CDB]:[AIBN]=600:1:0.3).
Example 6
Transformation of End Groups in a Bottle-Brush Copolymer and
Incorporation of a Second Functionality
[0097] The following reactions describe the experimental steps of
the Staundiger process for preparing amino terminated chains
(Scheme 4) exemplified by functionalizing the end groups of a
bottle brush copolymer prepared by ATRP. However the same approach
can be applied to any tele-functional polymers with terminal
halogen groups prepared by any controlled polymerization
process.
##STR00005##
Example 6a
Azidation of P(BPEM-graft-St) brushes (BS-02-18)
[0098] One gram of a bottle-brush copolymer with polystyrene grafts
at each monomer unit (BS-02-16-F, 0.28 mmol PS-Br endgroups) was
dissolved in DMF (11.3 mL) by stirring in a 20-mL scintillation
vial. NaN.sub.3 (0.037 g, 0.57 mmol) was added, and the vial was
sealed. The solution was allowed to stir for 24 h at room
temperature. The vial was opened to air and diluted with CHCl.sub.3
(10 mL). Water (20 mL) was added and the organic phase was washed
to remove unreacted NaN.sub.3. The organic phase was isolated and
washed (.times.2) with water (20 mL). The organic phase was dried
by passing through a syringe filled with approximately 5 mL (dry
volume) of MgSO.sub.4 and subsequent filtering with a syringe
filter. The solvent was removed by rotary evaporation and the
remaining solvent was dried under vacuum overnight to yield 0.78 g
(78%) of polymer (BS-02-18).
Example 6b
Hydrolysis of P(BPEM-graft-St-N.dbd.PPh3) Brushes (BS-02-21)
[0099] BS-02-20 (0.2 g, 0.050 mmol of --N.dbd.PPh.sub.3 endgroups)
was added to a 20-mL scintillation vial and THF (6 mL) was added
followed by 0.5 mL of water (large excess with respect to
endgroups) and the mixture was stirred in a sealed vial for 24
h.
[0100] The vial was opened, the mixture was filtered, and the
supernatant was collected. The filtered solid appeared to be a
polymer where each chain of the polymer brush was
amino-terminated.
Example 6c
Preparation of Iminophosphorane-Terminal Brushes from
P(Bpem-graft-St-N3) brushes (BS-02-20)
[0101] 0.5 g, of a bottle brush copolymer (BS-02-18) (0.127 mmol
PS--N.sub.3 endgroups) and dry THF (10 mL) were added to a 50-mL
round-bottomed flask. The polymer was allowed to dissolve under
constant stirring in the sealed flask. PPh.sub.3 (0.1 g, 0.382
mmol) was added and the flask was resealed and covered with
aluminum foil to keep solution in the dark. The solution was
allowed to stir for 36 h at room temperature. After this time, the
flask was opened to air and the polymer was isolated by
precipitation into n-hexanes. The polymer was filtered and dried
under vacuum to yield 0.35 g (70%) of polymer (BS-02-20).
[0102] Terminal functionality on a multifunctional branched or
graft copolymer prepared by a controlled polymerization process may
be modified to provide a different functionality than the
functionality required to grow the polymer segment.
Example 7
Chain Extension and Cyclization
[0103] The applicability of the high yield chemistry discussed
herein for the preparation of segmented copolymers is exemplified
by the preparation of homo- and heterotelechelic polystyrene
oligomers prepared by ATRP that are coupled or chain extended via a
step growth "click" process to yield moderate to high molecular
weight polymer containing 1,2,3-triazole linkages along the
backbone. While the synthetic strategy shown below indicates the
use of polystyrene, other (co)polymers could be employed and one or
more different telechelic materials could be chain extended in this
manner. Further the ether linkage between to two propargyl
functional groups can comprise other functionality, including
degradable functionality.
##STR00006##
[0104] Synthesis of .alpha.-acetylene-.omega.-azido terminated
polystyrene (7a) and its subsequent homocoupling (7b), and (7c)
synthesis of diazido-terminated polystyrene and (7d) its chain
extension coupling with propargyl ether.
[0105] .alpha.-Alkyne-.omega.-azido-terminated polySty was prepared
by ATRP of Sty with propargyl 2-bromoisobutyrate as an initiator
and subsequent post-polymerization nucleophilic substitution of the
bromine end groups by reaction with NaN.sub.3. The resulting
heterotelechelic polySty was subjected to a homo-click coupling or
chain extension reaction in DMF with CuBr as the catalyst. Click
coupling of the telechelic polySty (M.sub.n=850-2590 g/mol)
resulted in the preparation of moderate to high molecular weight
polymer (M.sub.n up to 61900 g/mol) with molecular weight
distributions characteristic of step growth polymers
(M.sub.w/M.sub.n2-5). The final polymer would have on average 24
triazole groups distributed along the backbone. However as shown in
FIG. 4 there was a fraction of the first telechelic polymer that
did not participate in the chain extension reaction and apparently
formed a lower molecular weight polymer. This is material that has
undergone an intramolecular coupling reaction and formed a cyclic
copolymer.
[0106] A one pot two step ATRP-nucleophilic substitution-click
coupling process also resulted in chain extension and some
cyclization.
[0107] .alpha.,.omega.-Diazido-terminated polySty was prepared by
ATRP of styrene with dimethyl 2,6-dibromoheptadioate as an
initiator followed by nucleophilic displacement of the bromine end
groups with NaN.sub.3. The resulting difunctional homotelechelic
polymer was copolymerized with propargyl ether at room temperature
to afford higher molecular weight polySty. Because the click
reaction was conducted in N,N-dimethylformamide (DMF), no
additional ligand was necessary to solubilize the CuBr
catalyst.
[0108] Based on .sup.1H NMR spectroscopy, the nucleophilic
substitution was complete within several hours for all three
approaches to chain extension. The amount of high-molecular weight
polymer in the mixture increased, although not all of the starting
material was consumed. The elution volume of the low-molecular
weight fraction in the product was slightly lower than the starting
heterotelechelic polystyrene, possibly indicating that cyclization
occurred since the hydrodynamic volume of the cyclic product
obtained by intramolecular self-coupling should be lower than the
parent polymer, and thus a lower apparent SEC molecular weight is
expected. The high extent of cyclization may be a result of DMF
being a rather poor solvent for PSt. The fraction of azide groups
in the product was small, which is expected since the concentration
of end groups decreases as coupling takes place, and each click
coupled chain should contain one azide and one alkyne end
group.
[0109] A chain extension intramolecular coupling chemistry
resulting in polymer cyclization can be converted into a high yield
intramolecular click coupling reaction yielding cyclic structures
by appropriate selection of the solvent. The propensity for
intramolecular reaction is increased for a collapsed polymer coil.
A poor solvent for the telechelic oligo/polymer results in the
formation of a "collapsed" molecular chain that preferentially
undergoes intramolecular reaction as evidenced by an apparent
decrease in the oligomer molecular weight measured by size
exclusion chromatography. The solvating power of a given solvent
can be modified by addition of a non-solvent to bring about this
change in the intra-molecular topology of the polymer in a given
solvent and thereby increase the yield of the intramolecular
coupling reaction.
Example 7a
Synthesis of Propargyl 2-bromoisobutyrate
[0110] Propargyl alcohol (12.8 mL, 0.218 mol) and 2-bromoisobutyric
acid (36.4 g, 0.218 mol) were dissolved in methylene chloride (150
mL). The reaction mixture was cooled in an ice-water bath and a
solution of dicyclohexyl carbodiimide (45.0 g, 0.22 mol) in
methylene chloride (50 mL) was slowly added while stirring. A
solution of 4-dimethylaminopyridine (1.5 g) in methylene chloride
(50 mL) was then added over a period of 10 min. The mixture was
stirred in the cooling bath for 1 h and then at room temperature
for 24 h. The precipitated dicyclohexylurea was filtered and washed
on the filter with methylene chloride (50 mL). The solvent was
removed on a rotary evaporator and the product was distilled under
vacuum. Yield: 33.0 g (0.161 mol, 74%). .sup.1H NMR spectrum in
CDCl.sub.3 (.delta., ppm): 4.77 (d, 2H, CH.sub.2O), 2.51 (t, 1H,
C.dbd.CH), and 1.96 (s, 6H, (CH.sub.3).sub.2C). IR spectrum (neat
liquid, NaCl plates): 3296 cm.sup.-1 (.nu..sub..dbd.C--H), 2131
cm.sup.-1 (.nu..sub.C.dbd.C), and 1741 cm.sup.-1
(.nu..sub.C.dbd.O).
Example 7b. Synthesis of .alpha.-alkyne-.omega.-bromo Terminated
Polystyrene; In-Situ Azidation and Click Coupling
[0111] A mixture of Sty (20 mL, 0.175 mol) and toluene (13.3 mL)
was degassed in a Schlenk flask by 5 freeze-pump-thaw cycles. CuBr
(0.0834 g, 0.58 mmol) was then added to the frozen mixture under
nitrogen flow and the flask was closed, evacuated and back-filled
with nitrogen. The vacuum-nitrogen cycle was repeated two more
times, and the mixture was allowed to melt. PMDETA (122 .mu.L, 0.58
mmol) was injected, and after formation of clear yellowish
solution, the reaction mixture was heated to 80.degree. C. in an
oil bath. The initiator PgBiB (0.34 mL, 2.326 mmol) was injected
and the reaction mixture was stirred at 80.degree. C. for 200 min.
The monomer conversion reached 13%. Half of the reaction mixture
was taken with a nitrogen purged syringe. The sample was diluted
with THE and the solution was passed through a column containing
neutral alumina in order to remove the catalyst. The absorbent in
the column was washed with THF (30-40 mL) and the polymer was
isolated by vacuum evaporation of the liquids. M.sub.n=850 g/mol,
M.sub.w/M.sub.n=1.03. The portion of the reaction mixture that
remained in the Schlenk flask was frozen by immersion in liquid
nitrogen. The flask was opened and sodium azide (0.76 g, 11.7 mmol)
and ascorbic acid, (to reduce the Cu.sup.II complexes formed during
the polymerization), (0.1 g, 0.57 mmol) were added under nitrogen
flow. The flask was closed, evacuated, and back-filled with
nitrogen. The mixture was thawed by immersion of the flask in hot
water, and deoxygenated DMF (10 mL) was injected. The resulting
heterogeneous mixture changed color from dark green to bright
greenish-yellow in several hours. Samples were withdrawn
periodically with a nitrogen-purged syringe and analyzed by size
exclusion chromatography (SEC). The presence of Sty and toluene did
not adversely affect the click coupling, which was rather
efficient, as judged by SEC analysis.
Example 7c
Preparation of .alpha.-alkyne-.alpha.-azido Terminated Polystyrene
and its Copper(I) Bromide-Catalyzed Click Coupling
[0112] A mixture of Sty (10 mL, 87 mmol), CuBr (0.32 g, 2.2 mmol),
propargyl 2-bromoisobutyrate (PgBiB) (0.32 mL, 2.2 mmol), and
diphenyl ether (1.1 mL) in a 25 mL Schlenk flask was subjected to
three freeze-pump-thaw cycles. The flask was placed in an oil bath
preheated to 90.degree. C., and PMDETA (0.46 mL, 2.2 mmol) was
injected via nitrogen-purged syringe. After 75 min, the flask was
removed from the heat, opened, diluted with THF, and passed through
a neutral alumina column to remove the catalyst. The absorbent in
the column was washed with THF (30-40 mL) and the resulting polymer
solution was concentrated by rotary evaporation. The polymer was
precipitated in methanol and dried under vacuum (M.sub.n=2590
g/mol, M.sub.w/M.sub.n=1.12). A fraction of the resulting polySty
(2.0 g, 0.77 mmol) and NaN.sub.3 (78 mg, 1.2 mmol) were dissolved
in DMF (12 mL) in a sealed 50 mL round-bottomed flask. The mixture
was allowed to stir at room temperature for 4 h, and the resulting
polymer was isolated by precipitation into methanol and drying
under vacuum. NMR spectroscopy indicated the conversion of
.alpha.,.omega.-dibromo- to .alpha.,.alpha.-diazidopolystyrene was
complete. A portion of the resulting polystyrene (0.5 g, 0.19 mmol
azide end groups) and CuBr (15 mg, 0.10 mmol) were added to a
Schlenk flask, and the vessel was subjected to three
vacuum-nitrogen cycles. Nitrogen-purged DMF (4 mL) was added, and
the mixture was allowed to stir at room temperature while samples
were withdrawn periodically via syringe to follow the increase in
molecular weight.
Example 7d
Synthesis of .alpha.,.omega.-diazido Terminated Polystyrene
[0113] A mixture of Sty (30 mL, 0.26 mol) and toluene (20 mL) was
degassed in a Schlenk flask by 5 freeze-pump-thaw cycles. The ATRP
catalyst was added as described above and consisted of CuBr (0.25
g, 1.7 mmol) and PMDETA (0.36 mL, 1.74 mmol). The difunctional
initiator, dimethyl 2,6-dibromoheptadioate DM-2,6-DBHD, (0.75 mL,
3.45 mmol) was added last, and the reaction was stirred at
80.degree. C. for 140 min. The monomer conversion reached 30%. The
reaction mixture was diluted with THF, and the solution was passed
through a column containing neutral alumina to remove the catalyst.
The absorbent in the column was washed with THF (30-40 mL), and the
resulting polymer solution was concentrated by rotary evaporation.
The polymer was precipitated in hexane and dried under vacuum
(M.sub.n=1900 g/mol, =1.09). Part of the product (1.9 g, 1.0 mmol,
corresponding to 2 mmol of bromine end-groups) was dissolved in DMF
(10 mL) and sodium azide (0.26 g, 40 mmol) was added. The mixture
was stirred for 4 h at room temperature and the polymer was
precipitated in methanol and dried under vacuum. NMR spectroscopy
indicated the conversion of .alpha.,.omega.-dibromo-to
.alpha.,.omega.-diazidopolystyrene was complete. The polymer was
analyzed by SEC: M.sub.n=2000 g/mol, M.sub.w/M.sub.n=1.08.
Example 7e
Click Coupling of .alpha.,.omega.-diazido Terminated Polystyrene
with Propargyl Ether
[0114] A mixture of 0.50 g of .alpha.,.omega.-diazido polystyrene
of M.sub.n=2000 g/mol (0.25 mmol, corresponding to 0.50 mmol of
azide groups) and 0.036 g (0.25 mmol) CuBr was placed in a flask
with a stir bar. The flask was then closed with a rubber septum,
evacuated and back-filled with nitrogen three times. DMF (3 mL,
deoxygenated by bubbling with nitrogen) was injected, and the
mixture was stirred until the polymer dissolved. Deoxygenated
propargyl ether (25.7 .mu.L, 0.25 mmol, corresponding to 0.50 mmol
of alkyne groups) was then added. The reaction mixture became
increasingly turbid and bright yellow in color. It was stirred at
room temperature while samples were periodically withdrawn via
nitrogen-purged syringe.
[0115] While propargyl ether was employed, other linking groups
between the two acetylene groups could be employed to further
introduce functionality into the copolymer. Of particular utility
would be functional groups that introduced a degradable linkage to
the material.
[0116] Further evidence of cyclization was evidenced by the limited
monomer conversion achieved at even long reaction times (A, Table
1). After 14.5 h the monomer conversion was 82% and increased to
only 83% at 89 h. Meanwhile, the coupling products continuously
increased in molecular weight, indicating that the conditions were
still appropriate for the reaction to take place. The reaction was
stopped and the polymer was analyzed by .sup.1H NMR spectroscopy
(FIG. 4). The fraction of residual azide groups in the product was
small, which is expected since the concentration of end groups
decreases as coupling takes place, and each click coupled chain
should contain one azide and one alkyne end group. As evidenced by
SEC, a small portion of higher molecular weight chains were present
in the starting material due to radical-radical termination during
ATRP. These chains contain two alkyne end groups and potentially
limit the degree of polymerization of the click coupled chains.
TABLE-US-00004 TABLE 1 Data from the Click Coupling of Hetero- and
Homotelechelic Polystyrene M.sub.n,.sub.app M.sub.w/M.sub.n
Polymerization Time (h) Monomer Conv..sup.d M.sub.n.sup.e
M.sub.w/M.sub.n.sup.e Monomer.sup.f Monomer.sup.f A.sup.a 0 0 -- --
2 590 1.11 14.5 0.82 15 500 2.43 1 920 1.04 21.5 0.82 15 600 2.35 1
900 1.04 89 0.83 21 500 4.85 1 920 1.04 C.sup.c 0 0 -- -- 2 020
1.09 16.5 0.93 13 700 2.77 1 570 1.03 24 0.93 14 800 3.15 1 540
1.03 40 0.93 16 700 3.34 1 550 1.03 .sup.aClick coupling of
.alpha.-alkyne-.omega.-azido-terminated polystyrene. .sup.bOne-pot
ATRP-nucleophilic substitution-click coupling of
.alpha.-alkyne-.omega.-azido-terminated polystyrene. .sup.cClick
coupling of .alpha.,.omega.-diazido-terminated polystyrene with
propargyl ether. .sup.dMonomer conversion determined by SEC.
.sup.eNumber average molecular weight and polydispersity of the
click coupled polymer as determined by SEC (PSty calibration) after
deconvolution of the polymer and monomer peaks. .sup.fNumber
average molecular weight and polydispersity of the difunctional
PSty monomer as determined by SEC (PSty calibration) after
deconvolution of the polymer and monomer peaks.
Example 7f
Preparation of a Chain Extended or Bottle Brush Block Copolymer by
Click Coupling from an Azido Chain End
[0117] The polymethylmethacrylate prepared in example 5d was
coupled to a diazido-polystyrene prepared in example 7d. The
reaction was conducted at a 1:1 ratio of functional groups in
dimethyl formamide solution at room temperature using copper
bromide as catalyst with no additional ligand. A block copolymer
was formed.
7 g
Preparation of a Chain Extended Tethered Nanocomposite
[0118] The terminal chain ends of a silica particle tethered
poly(butyl acrylate) nanocomposite, prepared as disclosed in U.S.
Pat. No. 6,627,314, were transformed into azido groups as disclosed
in example 7c and then the tethered chains of the composite were
chain extended by coupling with acetylene terminated poly(methyl
methacrylate). The size of the composite structure increased as
viewed by AFM images of the tethered block copolymer indicating
successful formation of attached block copolymer chains. Chain
extension was confirmed by GPC on the cleaved chains.
[0119] Embodiments of the present invention include selecting high
yield post-polymerization functionalization chemistry from high
yield chemistries to functionalize the first attached functional
group in a copolymer prepared by a controlled polymerization
process by initially selecting the functional groups on each
monomer or at each chain end to undergo reactions only with the
functional groups on the added reagent. Further the added agent can
comprise a third functionality which is thereby attached to the
first polymer. The third functionality can comprise oligo/polymeric
segments prepared by similar or different polymerization processes
and can include inorganic materials or organic materials including
bio-active or bio-responsive materials. Further the linking
chemistry can be utilized to form graft copolymers, block
copolymers, branched copolymers and linear copolymers with designed
distribution of polymer segments or materials attached to a
spectrum of substrate.
[0120] There have been several review articles where click
chemistry is discussed including: [0121] Hawker, C. J.; Wooley, K.
L. Advances in Dendritic Macromolecules 1995, 2, 1-39; [0122]
Matthews, O. A.; Shipway, A. N.; Stoddart, J. F. Progress in
Polymer Science 1998, 23, 1-56; [0123] Majoral, J.-P.; Caminade,
A.-M. Chemical Reviews (Washington, D.C.) 1999, 99, 845-880; [0124]
Grayson, S. M.; Frechet, J. M. J. Chemical Reviews (Washington,
D.C.) 2001, 101, 3819-3867.
[0125] Other high yield clean chemistry approaches have been
described: [0126] Maraval, V.; Pyzowski, J.; Caminade, A.-M.;
Majoral, J.-P. Journal of Organic Chemistry 2003, 68, 6043-6046.
describe a green chemistry method for dendrimer synthesis using
phosphaze hydrazine with only N2 or H2O as byproducts. [0127] Ihre,
H.; Padilla de Jesus, 0. L.; Frechet, J. M. J. Journal of the
American Chemical Society 2001, 123, 5908-5917 describe fast and
convenient divergent synthesis of aliphatic ester dendrimers by
anhydride coupling. [0128] Carnahan, M. A.; Grinstaff, M. W.
"Synthesis and Characterization of Poly(glycerol-succinic acid)
Dendrimers;" Macromolecules 2001, 34, 7648-7655. [0129] Wu, P.;
Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.; Voit, B.;
Pyun, J.; Frechet, J. M. J.; Sharpless, K. B.; Fokin, V. V.
"Efficiency and fidelity in a click-chemistry route to triazole
dendrimers by the copper(I)-catalyzed ligation of azides and
alkynes;" Angewandte Chemie, International Edition 2004, 43,
3928-3932. [0130] Helms, B. et. al. Journal of the American
Chemical Society 2004, 126, 15020-15021, "Dendronized Linear
Polymers via \"Click Chemistry\." [0131] Coltman, J. P.; Devaraj,
N. K.; Chidsey, C. E. D. "Huisgen 1,3-dipolar cycloadditions;"
Langmuir 2004, 20, 1051-1053.
* * * * *