Note: Descriptions are shown in the official language in which they were submitted.
~~~~~~3~~~
TO WHOM IT MAY CONCERN:
Be it known that We, David M. Hedstrand and Donald A.
Tomalia, both residing in the County of Midland, State of
Michigan, both citizens of the United States of America, have
invented new and useful improvements in
NON-CROSSLINKED, POLY-BRANCHED POLYMERS
for which the following is a specification and claims.
BACKGROUND OF THE INVENTION
This invention deals with non-crosslinked, poly-branched
lQ
polymers having a comb-burst configuration and a process for
preparing such polymers.
Macromolecular organic compounds having novel structures
have been investigated for many years as academic curiosities
and very little attention has been paid to their use in
industrial applications. Since the early i980is, there has
been a renewed interest in t';e study and development of such
macromolecular materials in order to control their critical
molecular design parameters, for example, size, shape,
surface chemistry, flexibility and topology, for use in
industrial applications. '."base materials have found such
'' 0
~5
diverse uses as demulsi.fier:~ For oil-in-water emulsions, as
wet strength agents in the manufacture of paper, as agents
for modifying ,~iscosities in aqueous formulations such as
paints and as ::ubmicron s~ze calibrators. Certain biological
,uses ra«e __=.1== :~eQ!~ =,~~:;e=-_?r ___ 'base materials.
Structurally, polymers are classified as either linear
or branched wherein the term "branched" generally means that
the individual molecular units of the branches are discrete
from the polymer backbone, fet may have the same chemical
constitution as the polymer backbone. Thus, regularly
repeating side groups which are inherent in the monomeric
structure and are of different chemical consitutution than
the polymer backbone are not considered as "branches", that
is, for example, the methyl groups pendent on a polydimethyl-
siloxane chain are not considered to be branches of that
1~ polymer.
In U.S. Patent 4,507,466, issued March 26, 1985, the
patentees therein described the prepartion of polymers having
"branching" in the following manner:
"TO produce a branched polymer, it is necessary to
1~ employ an initiator, a monomer, or both that possess at least
three moieties that function in the polymerization reaction.
Such monomer or initiators are often called polyfunctional.
The simplest branched polymers are the chain branched
polymers wherein a linear backbone bears one or more
essentially linear pendant aroups. This simple form of
branching, often called comb i~ranching, may be regular
wherein the branches are uniformly and regularly distributed
on the polymer backbone or irregular wherein the branches are
distributed in non-uniform or random fashion on the polymer
backbone." "An example of regw~~ar comb branching is a comb
2
~c~~~~~~~'.
branched polystyrene as described by T. Altores et al. in J.
Polymer Sci., Part A, Vol. 3 4131-4151 (1965) and an example
of irregular comb branching is illustrated by graft
copolymers as described by Sorenson et al. in "Preparative
Methods of Polymer Chemistry", 2nd Ed., Interscience
Publishers, 213-214 (1968).
Another type of branching is exemplified by crosslinked
or network polymers wherein the polymer chains are connected
via tetravalent compounds, e.g., polystyrene molecules
bridged or cross-linked with divinylbenzene. In this type of
lu branching, many of the individual branches are not linear in
that each branch may itself contain groups pendant from a
linear chain. More importantly in network branching, each
polymer macromolecule (backbone) is cross-linked at two or
more sites to other polymer macromolecules. Also the
'-~ chemical constitution of the cross-linkages may vary from
that of the polymer macromolecules. In this so-called cross-
linked or network branched polymer, the various branches or
cross-linkages may be structurally similar (called regular
cross-linked) or they may be structurally dissimilar (called
irregularly cross-linked). An example of regular cross-linked
polymers is a ladder-type poly(phenylsilsesquinone) (sic)
(poly(phenylsilsesquioxane)j."
Sogah, et al., in the background of U.S. Paten't
4,544,24, ;ssued October i. =985, discusses some of these
J
c~
types of polymers and gives a short review of the many
publications and disclosures regarding them.
One of the inventors herein, Donald A. Tomalia, and many
of his co-workers have been working in this field for several
years and have issued many patents which disclose various
non-crosslinked, macromolecular branched assemblies.
For example, U.S. Patent 4.435,548, issued March 6, 1984
discusses branched polyamidoamines; U.S. Patent 4,507,466,
issued March 26, 1985, U.S. Patent 4,558,120, issued December
10, 1985, U.S. Patent 4,568,737, issued February 4, 1986,
U.S. Patent 4,587,329, issued May 6, 1986, U.S. 4,713,975,
issued December 22, 1987, U.S. Patent 4,871,779, issued
October 3, 1989, and U.S. Patent 4,631,337, issued December
23, 1986, discuss the preparation and use of dense star
polymers, and U.S. Patent 4,737,550, issued April 12, 1988
1~ and U.S. Patent 4,857,599, issued August 15, 1989, discuss
bridged and other modified dense star polymers.
Also, other structural configurations of macromolecular
materials that have been disclosed include star/comb-branched
polymers, such disclosure being found in U.S. Patents
4,599,400, issued July 8, 1986 and U.S. Patent 4,690,985,
issued September 1, 1987, and finally, rod-shaped dendrimer
polymers are disclosed in tJ.S. Patent 4,694,064, issued
September 15, 1987.
The polyamidoamines referrAd to supra are also disclosed
=5 ~.n U.S. Patent 4,758,635, issued "uly 19, 1988 to Wilson et
al.
CA 02049643 2002-08-02
64693-5449
Hutchins, et al, in U.S. Patents 4,847,328, issued
July 11, 1989 and U.S. Patent 4,851,477, issued July 25,
1989, deal with hybrid acrylic-condensation star polymers
and Joseph et al in U.S. Patents 4,857,615, issued August
15, 1989, U.S. Patent 4,857,618, issued August 15, 1989, and
U.S. Patent 4,906,691, issued March 6, 1990, deal with
condensed phase polymers which are linear polymers having
regularly, or irregularly, spaced polymeric branches,
essentially on the order of a comb structure macromolecule.
An excellent presentation of the structures and
chemistries of many such macromolecular branched assemblies
can be found in Tomalia, D.A., Naylor, A.M., and Goddard,
W.A. III, Angewandte Chemie, 29/2 (1990), pages 138 to 175.
However, none of the disclosures of the prior art
deal with the novel polymers of the instant invention which
are non-crosslinked, poly-branched polymers. For simplicity
sake, the polymers of the instant invention can be generally
characterized as multiple polymeric branches on multiple
polymeric branches.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a schematic in two dimensions of the
polymer configuration of the polymers of the instant
invention wherein
1 is the initiator core (initiator core molecule);
2 is first grafting and first branching and
generation 0;
5
3 is second grafting and second branching and
generation 1;
4 is third grafting and third branching and
generation 2;
is fourth grafting and fourth branching and
generation 3;
6 is (i + 1)'" grafting and (i + 1)'" branching and
generation i, and
7 is (i + 2)'" and all iterative grafting and
(i + 2)'" and all interative branching, and
generation (i + 1) and all subsequent generations.
THE INVENTION
Benefits and other perceived advantages are achieved in
accord with the present invention which comprises novel non-
crosslinked, poly-branched polymers, and methods for
manufacturing such polymers. In its broadest scope, this
invention deals with poly-branched polymers having at least
one branch referred to herein as a "core branch" emanating
from a core molecule, said branch being essentially linear,
and having at least one end chemically coupled to the core
molecule, with the other end of the branch terminating in a
group from a molecule used to initiate the reaction by which
the branch was prepared, and at least one second branch which
is branched from the yore branch, said second branch, or
branches, being ~ss2ntiallr _.i:.ear, and having at least one
end chemically coupled to the core branch, with the other end
~S
0
CA 02049643 2003-O1-17
64693-5449
of the branch terminating in a group selected from a
molecule used to prepare the second branch polymer, which
when subjected to iterative polymer grafting steps (i.e.
generations, which will be delineated further herein), form
three-dimensional organizations of ordered organic
molecules. These polymers are hereinafter referred to as
"comb-burst" structures in that they are prepared from comb-
like core molecules, but after subsequent grafting of
additional branches pursuant to the processes of this
invention, tend to have the appearance in two dimensions of
.a woven wire fence, which when viewed in three dimensions
gives a topology having a starburst-like appearance. Hence,
"comb-burst".
According to one aspect of the present invention,
there is provided a composition of matter comprising non-
crosslinked poly-branched polymers having the general
.Formula
R°,~~q° )-_~g°)}n~Gc
I
to
G
I
~~A°)- ~ CB°)}n°Ro
11
G
i
f (A1)- ~ (B1)}ni Ri
12
G
I
~ ~Az )- ~ ~Bz ) }n2 Rz
13
G
I
~ ~A3 )- I ~B3 ) }n3 R3
I.
G'
' ) _ ~ ( g' ) }n' Ri
7
CA 02049643 2003-09-17
64693-5449
wherein R° is a non-reactive end group and each R°, R1, Rz,
R3, and Ri is a residual moiety derived from initiators
selected from a group consisting of free radical initiators,
cationic initiators, anionic initiators, and group transfer
initiators; i represents repetitive linear polymers having
the unit formula { (A1) -- (Bl) } ; A°, A°, Al, Az, A3, and A1
are
non-reactive comonomers or, oligomers or polymers formed
from a polymerizable monomer, said oligomers or polymers
being capable of withstanding the conditions required for
preparation of a graft polymer; B°, B°, B1, Bz, B3, and Bi are
protected or unprotected reactive nucleophilic or
electrophilic monomers, or oligomers or polymers formed from
a polymerizable monomer, said oligomers or polymers being
capable of withstanding the conditions required for
preparation of a graft polymer; G°, Gl, Gz, G3 and Gi are
grafting components which represent bonding between adjacent
units of the repetitive linear polymers, said bonding being
to either an A segment or a B segment; G is a terminating
group; n° is the degree of polymerization of a core
initiator; n° is the degree of polymerization of a first comb
branch; nl is the degree of polymerization of a first
generation comb-burst branch; nz is the degree of
polymerization of a second generation comb-burst branch; n3
is the degree of polymerization of a third generation comb-
burst branch; ni is the degree of polymerization of the itn
generation comb-burst polymer having at least one branch
point; wherein ni > 2 for the case where i = c, °, and 1, and
nl > 2 if nl-1 is > zero, the largest i for which nl does not
equal zero is the total number of generational levels of the
polymer wherein the superscripts c, °, 1, 2, 3 and i
designate comb-burst generation level; the unit ratio of A
segments to B segments in any {(A)--(B)} segment of the
polymer is 0 to 1:100 to 1.
7a
CA 02049643 2003-09-17
64693-5449
According to another aspect of the present
invention, there is provided a process for preparing non-
crosslinked poly-branched polymers having the general
formula
Rc-{(Ac )--(gc)}ncGc
I
Go
i
{(A°)- ~ (B°)}n°Ro
I
G
I
{ (A1 )- ~ (B1 ) }n1 Ri
Iz
G
I
{ (Az )- ~ (Bz ) }nz Rz
I3
G
{ (A3 )- I (B3 ) }n3 R3
I.
G'
I
{ ( A~ ) - I ( g ~ ) }n~ Ri
wherein R° is a non-reactive end group and each R°, Rl, Rz,
R3, and R~ is a residual moiety derived from initiators
selected from a group consisting of free radical initiators,
cationic initiators, anionic initiators, and group transfer
initiators; i represents repetitive linear polymers having
the unit formula ~ (Al)-(Bl) }; Ac, A°, Al, Az, A3, and Al are
non-reactive comonomers or, oligomers or polymers formed
from a polymerizable monomer, said oligomers or polymers
being capable of withstanding the conditions required for
preparation of a graft polymer; B°, B°, B1, Bz, B3, and Bi are
protected or unprotected reactive nucleophilic or
electrophilic monomers, or oligomers or polymers formed from
a polymerizable monomer, said oligomers or polymers being
capable of withstanding the conditions required for
7b
CA 02049643 2003-O1-17
64693-5449
preparation of a graft polymer; G°, G1, G2, G3 and Gl are
grafting components which represent bonding between adjacent
units of the repetitive linear polymers, said bonding being
to either an A segment or a B segment; G° is a terminating
group; n° is the degree of polymerization of a core
initiator; n° is the degree of polymerization of a first comb
branch; nl is the degree of polymerization of a first
generation comb-burst branch; n2 is the degree of
polymerization of a second generation comb-burst branch; n3
is the degree of polymerization of a third generation comb-
:burst branch; ni is the degree of polymerization of the ith
generation comb-burst polymer having at least one branch
point; wherein nl > 2 for the case where i = c, °, and 1, and
nl > 2 if nl-1 is > zero, the largest i for which ni does not
equal zero is the total number of generational levels of the
polymer wherein the superscripts c, °, 1, 2, 3, and i
designate comb-burst generation level; the unit ratio of A
segments to B segments in any {(A)--(B)} segment of the
polymer is 0 to 1:100 to 1, the process comprising (I)
i=orming a linear initiator core having at least one reactive
site and having the general formula
R°-{ (A°) - (B°) }n° G°;
(II) reacting essentially all of the sites (B°) of (I) with a
x-eactive polymer having the unit formula G°{ (A°) - (B°)
}n°R° to
form multiple branches that contain at least one multiple
reactive site on each branch using protection-deprotection
reactions to ensure that the unit formula G°{ (A°) - (B°)
}n°R°
reacts with all (B°) sites of (I) but that no reactions occur
at the reactive sites B°; (III) repeat (II) sequentially to
form successive generations of reactive branches to give the
desired non-crosslinked poly-branched polymers.
7c
CA 02049643 2003-O1-17
64693-5449
This invention therefore comprises a composition
of matter comprising non-crosslinked poly-branched polymers
having the general formula
Rc-_{(Ac )_-(gc)}ncGc
I
Go
I
{(A°)- ~ (B°)}n°Ro
11
G
~(A1)- ~ (B1)}nl Ri
Gz
i
{ (AZ )- ~ (BZ ) }n2 Rz
13
G
I
- ~ (B3 ) }n3 R3
I.
G'
i
{ ( A~ ) - ~ ( g' ) }ni Ri
7d
CA 02049643 2003-09-17
64693-5449
wherein R° is a non-reactive end group and each R°, R1, R2,
R3, and Ri is selected from initiators selected from a group
consisting of free radical initiators, cationic initiators,
anionic initiators, and group transfer initiators;
i represents repetitive linear polymers having the unit
formula { (A1) -- (B1) ~ ; A°, A°, Al, A2, A3, and A1 are non-
reactive comonomers or, oligomers or polymers formed from a
polymerizable monomer, said oligomers or polymers being
capable of withstanding the conditions required for
preparation of a graft polymer; B°, B°, B1, B2, B3, and Bi are
protected or unprotected reactive nucleophilic or
electrophilic monomers or, oligomers or polymers formed from
a polymerizable monomer, said oligomers or polymers being
capable of withstanding the conditions required for
preparation of a graft polymer; G is a terminating group or
a grafting component; n° is the degree of polymerization of a
core initiator; n° is the degree of polymerization of a first
comb branch; nl is the degree of polymerization of a first
generation comb-burst branch; n2 is the degree of
polymerization of a second generation comb-burst branch; n3
is the degree of polymerization of a third generation comb-
burst branch, nl is the degree of polymerization of the itn
generation comb-burst polymer having at least one branch
point; wherein nl >- 2 for the case where i = c, °, and 1, and
ni >- 2 if nl-1 is > zero, the largest i for which ni does not
equal zero is the total generation level of the polymer
8
2~3~~~~.4~
wherein the superscripts c, °, l, 2, 3, and i designate comb-
burst generation level; the unit ratio of A units to B units
in any {(A)--(B){ segment of the polymer is 0 to 1:100 to 1.
As indicated above, each of R°, R', R', R', and R' in
these inventive polymers is selected as a moiety from a
radical initiator, a moiety from a cationic initiator, a
moiety from an anionic initiator, or a group transfer
initiator. R°- R' can be for example hydrogen, an alkyl
group, Lewis acids, or the like.
The G' group is the grafting component formed by the
reaction of the living end, or a derivative of the living
end, of the i'" generation oligomer with the reactive groups
of the (i-1) generation material. Thus, an anionic oligomer
may be reacted directly with an electrophilic precursor
generation, or it may be terminated by, for example, a
l~ halogen such as chlorine, bromine, or iodine, to create an
electrophilic end group for grafting to a nucleophilic
precursor. Similarly, a cationic oligomer may be reacted
directly with a nucleophilic precursor generation, or
terminated with, for example, water, hydrogen sulfide, or an
20 amine to give a nucleophilic end group for reaction with an
electrophilic precursor. In the case of G°, the "graft" is
to a monofunctional molecule, which may be as simple as
quenching the active end with ,~ proton or hydroxide, as would
be the case with normal termznatioll Of ionic oligomers with
.S water, or trapping wit: a cp~c~f~:, mclecule in order to
a
introduce a single desired functional group to the molecule.
Other telechelic groups suitable for grafting purposes may be
found in Goethals, "Telechelic Polymers"; Syn. Appln., CRC
Press (1989).
The oligomeric and polymeric segments of these materials
can be homopolymers or copolymers, it being understood that
the formulae herein represent bonding of the grafting G
groups to either segment A, if it is present, or to segment
B, and it being further understood that the grafting to any A
segment is at the terminal end of the molecule, any other
segment A grafting would result in the potential for
crosslinking the polymers, which is not part of the invention
herein. Also, for purposes of this invention, each A segment
can be monomeric or, oligomers or polymers formed from
polymerizable monomers, the only condition being that the
1~ said monomers, oligomers and polymers must be capable of
withstanding the conditions reauired for preparation of
subsequent graft junctures. As illustrated in the formulae,
the bond from G to the next generation is indicated by a
vertical line about halfway between the A segments and the B
'_0 segments to illustrate that G can be bonded to either A, if
it is present, or to B, which is always present in the
molecule.
Segments of A include for ~:cample, -CHZ CHZ -,
-Cii, Ca=CHCH~ - , -CH, C ( f iT, ) : - , .. ' ~:? ( CN ) - , -CH, CH- , -CHi
CH- ,
i i
__ C=O 0
NHZ R
.'J
-CH, CH- -NCHZ CHZ - , -NCHZ CHZ CHZ - , -OCHZ CHZ - , - SCH= CH= - ,
0 C=0 C=O
C=0 R R
R
-R'2Si0-, -CH,CH-, -OCHZCH-, wherein R' is an alkyl group of
C5 H5 CHI
OR
1 to 4 carbon atoms, aryls, arylalkyl, hydrogen, or
carboalkoxy and R is an alkyl group of 1 to 4 carbon atoms,
aryls, or hydrogen;
R
-CH2 C-_-,
COZ R"
wherein R has the same meaning as set forth above,
and wherein R" can be an alkyl group of 1 to 4 carbon atoms.
Preferred as A segments are -CH, CHZ -, -NCHZ CHZ _ ,
i
C=0
R
-CHZ C ( CH, ) z - , -CHZ CH- , -CH2 CH, O- , -CHZ CH2 S- , -CHZ CH=CHCH2 - ,
C=O
NH2
-R'ZSiO-, -CHZCH-, and -CH,C-. Most preferred are the A
i
C6 HS R,
segments -NCH7 CHz - , -CHZ CH- , and -CHz CH-
C=O ' '
R C6 HS C5 H, CH,
Each B segment can be monomeric, or oligomers or
poiymex~s formed from potymPrizable monomers, wherein said
monomers, oligomers and rol~rn;ers oust be capable of
11
CA 02049643 2000-12-07
withstanding the conditions required for preparation of a
graft polymer and further, the B segments must contain at
least one unit which is nucleophilic or electrophilic in
character.
The groups B contain the reactive sites to which the
oligomers may be grafted. In many cases, these groups may
need to be present in latent or masked form if they would
otherwise be incompatible with the oligomerization process.
For example, polymerization of ethyleneimine leads to highly
branched polyethyleneimine oligomers which are not useful for
this invention because the secondary amines formed are also
reactive under the polymerization conditions. Oxazoline
polymerization leads to linear polyethyleneimine in a
protected form, and the secondary amines can be unmasked for
grafting by hydrolysis. For alkylene oxide oligomerizations,
hydroxyl groups intended for use as future graft sites would
need to be masked as, for example, an ether to preclude the
possibility of forming highly cross-linked gel systems. An
example of a latent reactive site would be an alcohol group
of a polyol which would require activation by conversion to a
halide or sulfonate to allow reaction with anionic oligomer.
Thus, B as a nucleophile can be selected from such
group s a s -NCHZ CHz , -CHZ CH- , -CHZ CH ( OH ) - , -CHZ CH ( SH ) - ,
i
H NHR
-OCHZ CH ( CHz OH ) - , and -NCHz CHz CHZ - , whi 1 a B as an
H
electrophile can be selected from such groups as
12
-CH, CH-- , -CHZ CH-- , -CH, CH-- , -OCHZ CH-- ,
i
CH= C1 CHz ( tosylate ) COZ R" CH, C1
R R
-CH~CH,CH---- , -Si0-, and -Si0--, wherein R and R" have
CH2 C 1 C 1 CH, C 1
the meanings set forth above.
It should be understood that homopolymers consist of
only the B segment, while copolymers can be had by combining
the B segments with the A segments. Copolymers can also be
prepared by using different monomers for the B segment of
different generations, for example B' being different from
BZ .
The inventors herein contemplate that for purposes of
this invention, there must be at least one B segment and
therefore the ratio of A segments to B segments ranges from 0
to 1 to 100 to 1.
This invention also comprises a process for preparing
non-crosslinked poly-branched polymers having the general
formula
~5
,z
~~~~~i4~
R° _ ~ (p,' )--(B° ) )~' G'
Go
f(A°)-;(~°)~r° R°
G'
~ (A' )-i (B' ) I"' R'
GZ
I(Az)-~(B2)I~z RZ
G'
I (A' )-i (B' ) ~"' R'
G'
((A)' -~(B')~~i R'
wherein R° is a non-reactive end group and wherein each R°,
R', R~, R', and R' is selected from initiator types selected
from a group consisting of free radical initiators, cationic
initiators, anionic initiators, and group transfer
initiators; (i) represents repetitive linear polymers having
the unit formula ( (A' )--(B' ) j ; A' , A°, A' , AZ , A' , and A' are
non-reactive comonomers or, oligomers or polymers formed from
a polymerizable monomer, said oligomers or polymers being
capable of withstanding the conditions required for
preparation of a graft polymer; B' , B°, B1 , B' , B' , and B'
are protected or unprotected reactive nucleophilic or
electrophilic monomers or, oligomers or polymers formed from
~5
a polymerizable monomer, said ol_~;omers or polymers being
capable of withstanding yhe condi~:ions raquired fox
preparation of a graft polymer; G is a terminating group or a
'a
grafting component; n' is the degree of polymerization of a
core initiator; n° is the degree of polymerization of a first
comb branch; nl is the degree of polymerization of a first
generation comb-burst branch; n= is the degree of
polymerization of a second generation comb-burst branch; n'
is the degree of polymerization of a third generation comb-
burst branch, n' is the degree of polymerization of the i'"
generation comb-burst polymer having at least one branch
point; wherein n' > 2 for the case where i = c, °, and 1, and
n~ > 2 if n''' is > zero, the largest i for which n' does not
e~al zero is the total generation level of the polymer
wherein the superscripts c, °, 1, 2, 3, and i designate comb-
burst generation level; the unit ratio of A units to B units
in any ((A)--(B)} segment of the polymer is 0 to 1:100 to 1,
the process comprising (I) forming a linear initiator core
having at least one reacti~,re site and having the general
formula
R° - F ( A~ ) __ ( B° ) } n' G= ; ( I I ) reacting all or
part of the sites
(B°) of (I) with a reactive polymer having the unit formula
G°((A°)--(B°)jn°R° to form multiple
branches that contain at
0 least one reactive site on each branch using protection-
deprotection reactions to ensure that the unit formula
G°((A°)--(B°)~n°R° reacts only with (B')
sites of (I) and
that no reactions occur at the reacti~re sites B°; (III)
-epeat ;T_I) equentialll ~o lcr~a successive generations of
.,5 reactive branches to give the desired non-crosslinked poly-
branched polymers. IS
CA 02049643 2002-08-02
64693-5449
It should be noted by those skilled in the art
that the polymer requires an initiator core (initiator core
molecule). This initiator core may or may not be a "living
polymer" or "living oligomer", which oligomers and/or
polymers are generally known to those skilled in the art.
"Living systems" are preferred in order to control
polydispersity of the comb-burst dendrimers. Using specific
chemistry, the inventors herein can explain this aspect of
the invention beginning with reference to "Polymeric Amines
And Ammonium Salts", edited by E.J. Goethals, Pergamon
Press, (1980), with especial reference to pages 55 et seq.
wherein there is taught one method of producing living
polymers in a paper entitled "Linear Polyalkylenimines",
Saegusa, T. and Kobayashi, S.
Using the example of Saegusa, page 58, one can
observe that an initiator such as methyl iodide is first
reacted with an oxazoline in the following sequence to give
an oligomeric "living oligomer" having, in this case, two
protected reactive sites designated as
NCH2CH2
C 0
H
H Me N H
N
MeI + ~ C +'~ ~ I- --~ MeNCH2CH2 I -->
0 0
HC 0
16
CA 02049643 2002-08-02
64693-5449
Me
H
H I N\ ~ NCHzCHZ N _ H
MeNCH2C 2 + ~~ -
0 +,, I_
~0
HC 0 HC 0
that is, Me(NCHZCHZ)2 I
HC 0
With further reference to Fig. 1 of the instant
invention, the initiator core in the specific case described
just above would be shown in Fig. 1 as R° (B°) nc G°;
where R°
is methyl and G° is as described above.
Reaction sequences are then chosen to deprotect
the nitrogen groups so that each of the two reactive sites
adds a reactant possessing its own, new reactive site, or
sites, which introduces multiplicity, to obtain a
"dendrimer" -{ (A°) - (B°) }n°-R° of generation o
(see Fig. 1) ,
wherein "dendrimer" has the same or similar meaning as that
used by Tomalia, et. al. in the article referenced supra.
As can be observed from the reaction sequence set forth
above, this process requires that protection-deprotection
strategies are used to ensure that the reactant reacts with
all reactive (B°) sites, but does not react any (B°) sites.
Protection-deprotection strategies are generally known to
those skilled in the art and great detail does not have to
be set forth here. Suffice it to suggest that the living
oligomer set forth above has the protective group
HC 0 on each nitrogen
17
of the oligomer whereupon the oligomer is then hydrolyzed
with an acid to give polymeric units having reactive amine
groups i.e.
Me- ( NCHZ CHZ - ) ~ - I
H
which are then used as the reactive sites to form the next
generation, it being understood that the reactive sites of
the polymer being grafted to the amine groups are protected
before this reaction takes place, and that they too are
hydrolyzed after the grafting reaction to give additional
reactive sites for the next generation of branching.
Additional iterative sequences involving addition of new
reactants having reactive sites is then undertaken in order
to add branches onto branches to form the poly-branched
polymer of this invention until the polymers will not form
due to steric hinderence referred to as comb-burst dense
packing. The article by Tomalia, et al, referenced supra
sets forth such technical terms.
One of the inventive processes used to prepare polymers
of this invention relies on the polymerization of 2-ethyl-2-
oxazoline. Methyl p-toluenesulfonate has been shown to
polymerize oxazolines and the polymerization mechanism has
been determined to be cationic, producing a "living polymer".
This allows the preparation of polymer samples with well
defined molecular weight and low polydispersity. The end of
the growing polymer chain contains an oxazolinium ion as
18
L t
disclosed above, that can be trapped by a variety of
nucleophiles. To graft the living poly(2-ethyl-2-oxazoline)
chains, they are terminated with the secondary amine groups
contained on linear poly(ethyleneimine)(LPEI). After
grafting onto the linear poly(ethyleneimine) has been
accomplished, hydrolysis of the poly(2-ethyl-2-oxazoline)
grafts will generate poly(ethyleneimine) branches. This
allows further living poly(2-ethyl-2-oxazoline) chains to be
grafted onto the poly(ethyleneimine) branches. Repetition of
the grafting and hydrolysis forms the inventive polymers with
the structures shown herein.
Example 1
A 250 ml one-necked round-bottomed flask equipped with a
magnetic stirring bar and a Dean-Stark trap that was
surmounted with a reflux condenser was charged with 2.84 gm
1~ (15.3 mmole) of methyl tosylate and 125 ml of toluene. The
mixture was heated at reflux and solvent was collected until
all water had been removed. At this time, 30.0 gm (303
mmoles) of freshly distilled 2-ethyl-2-oxazoline was added
all at once and the mixture was refluxed for approximately 4
hours. During this time, in a separate flask, 1.64 gm (38.1
mmole of repeat units) of linear poly(ethyleneimine) was
azeotropically dried with toluene. when the poly(ethylene-
imine) was dry it was added ',:o the round-bottomed flask
containing the oxazoline oligomer end then allowed to reflux
'? S
19
for an additional 3 hours. Any ungrafted living poly(2-
ethyl-2-oxazoline) chains were neutralized by the addition of
2.0 ml of water with refluxing for an additional 1 hour.
Toluene was removed under reduced pressure to leave a
yellowish oily solid that was dissolved in chloroform and
' precipitated dropwise into diethyl ether. The yellow solid
was filtered from solution and dried overnight in a vacuum
oven to yield 29.7 gm (94% yield) of grafted poly(2-ethyl-2-
oxazoline) as a yellow powder.
Example 2
Into a 500 ml one-necked round-bottomed flask was placed
21.6 gm of the oxazoline from example 1 and 350 ml of water.
When the polymer had completely dissolved, 35 ml of
concentrated sulfuric acid was added. The flask was equipped
with a distillation head and the mixture was heated at reflux
and distillate was collected until propionic acid could not
be detected. Water was added to the distilling pot when the
volume was reduced to less than approximately 75 ml. Upon
removal of the propionic acid the distillation head was
replaced with a reflux condenser surmounted with a pressure
equalized addition funnel charged with 5N NaOH. The base was
slowly dripped into the reaction mixture maintained at
reflux. When the pH of the reaction mixture was
approximately 12, heating was discontinued. At room
temperature a solid had formed 3t the surface of the aqueous
' mixture. This precipitate was removed and placed in a 250 ml
~0
~?~~~~~~.~3
round-bottomed flask with 175 ml of toluene. The water was
removed from the water-toluene azeotrope by distillation.
When water removal was complete, the solid became soluble in
the refluxing toluene. The hot toluene solution was poured
into a 250 ml round-bottomed flask leaving behind insoluble
salts. Toluene was removed under reduced pressure to leave a
brownish, waxy solid. The sample was dried for approximately
24 hours under vacuum to give 9.14 gm (97% yield) of polymer
sample.
Example 3
lp Using the general method of Example 2, hydrolysis of the
graft polymers, was carried out on a separate batch of the
graft polymers in the following manner. Five grams (5.0 gm)
of the graft copolymer were placed in a 250 ml round-bottomed
flask with 100 ml of water and 10 gm of sulfuric acid. The
S flask was heated with a heating mantle to give a slow
distillation of the propionic acid/water azeotrope. The
distillation was continued for 2 days, with water being added
as necessary to maintain the reaction volume. Approximately
200 ml of distillate was collected over the course of the
p hydrolysis. The heating was discontinued and 50% NaOH was
added slowly to bring the pH to 10. The free polyamine was
insoluble in the saturated salt solution, giving a separate
phase on top of the aqueous solut'_on. The phases were
separated and the polyamine was placed in a 250 ml round-
bottomed flask. One hundred f=fty T1 of toluene was added and
~1
a Dean-Stark trap was attached. After reflux overnight
(about 16 hours), no more water was being removed and the
polyamine had dissolved in the hot toluene. The hot solution
was filtered and the solvent was removed from the filtrate
using vacuum and agitation to give branched
poly(ethyleneimine) weighing 2.2 gm (100% of theory) as an
orange oil. The " C-NMR spectrum showed a peak for linear
poly(ethyleneimine) (49.4 ppm/intensity 8075), residual
unhydrolyzed propionamide (9.5 ppm/intensity 156),(26.3
ppm/intensity 180), and primary amine end group (41.7
ppm/intensity 61). No peak for a hydroxy terminal group was
observed. While the intensities may not be interpreted as a
quantitative measure of the groups present, qualitatively,
hydrolysis was 80 to 90% complete and grafting was complete
within the limits of detection.
Example 4
A 2 liter, 3-necked, round-bottomed, glass flask was
used with a shaft driven stirrer, instead of magnetic
stirring. The initial loading was: water - 250 ml, material
prepared essentially by the method of example 3 - 125 gm,
sulfuric acid - 150 gm. Additional sulfuric acid, 100 gm was
added halfway through the hydrolysis to improve solubility.
Internal flask temperature was monitored and a solenoid valve
was rigged to add water whenever the temperature rose above
107"C. Thus, constant attention was not necessary and the
_5 distillation could be left unattended overnight. The heating
22
CA 02049643 2002-08-02
64693-5449
mantle was also set to shut off at the same temperature so
that the flask would not overheat if the water reservoir ran
out of water. After 2 days of continuous distillation, 1.6
liters of distillate was collected. The reaction mixture
was neutralized and the polymer phase was separated. The
crude polymer was purified by dissolving in hot water
(1 liter) and precipitated by slow addition to cold water.
After two precipitations, the supernatant solution was
neutral to HydrionR paper. The resulting hydrated polymer
was dehydrated via toluene azeotrope as described above to
give LPEI (51 gm 94°s yield). The 13C-NMR spectrum showed
LPEI with residual amide carbon intensities 0.5~ of the LPEI
intensity. Primary amine end group intensity was 0.4% of
the LPEI intensity.
Example 5
Into a 250 ml round-bottomed glass flask was
placed p-toluenesulfonic acid monohydrate (2.0 gm, 11 mmole)
and toluene (100 ml). A Dean-Stark trap was attached and
the mixture was heated at reflux until water removal was
complete. Ethyl oxazoline (10 gm, 100 mmole) was added all _
at once and the reflux was continued for 2 hours. LPEI (1.0
gm, 23 meq.) was placed in toluene (25 ml) and the mixture
was heated to boiling to dissolve the polymer and
azeotropically remove trace water in the polymer. The hot
LPEI solution was added all at once, to the cloudy oligomer
suspension. An orange oil began to precipitate immediately.
After 1 hour at reflux, the mixture was cooled and the
solvent stripped using vacuum. The residue was dissolved in
CH2C12 (40 ml) and precipitated by a slow addition to ether
(500 ml). The solid was collected by filtration and dried
in a vacuum oven at 40° to 50°C to give the grafted polymer
(12 gm, 92~ yield) as a yellow powder. At higher M/I
23
CA 02049643 2002-08-02
64693-5449
ratios, the oligomerization time had to be increased to
allow complete conversion of the ETOX. For example,
intermediate degree of polymerization runs (M/I = 200, olig.
time = 3 hours or M/I = 400, olig. time = 6 hours) had low
yields due to incomplete conversion. Increasing the
reaction time to 12 hours and 24 hours respectively, gave
higher conversions and yields. The highest M/I (1000) run,
had an oligomerization time of 36 hours, which was not long
enough for complete conversion. This gave a material with
actual oligomer dp of 700. The 13C-NMR spectrum of the
poly-branched polymer derived from this material showed a
peak for primary amine end groups which was approaching the
limits of detection for the signal/noise ratio. No hydroxyl
terminal group was detectable.
24
