Towards a universal polymer backbone: Design and synthesis of polymeric scaffolds containing terminal hydrogen-bonding recognition motifs at each repeating unit

Article abstract of DOI:10.1002/chem.200390122

Polymers containing terminal hydrogen-bonding recognition motifs based on diaminotriazine and diaminopyridine groups in their side chains for the self-assembly of appropriate receptors have been prepared by ring-opening metathesis polymerization (ROMP) of

Full text of DOI:10.1002/chem.200390122

FULL PAPER
Towards a Universal Polymer Backbone: Design and Synthesis of Polymeric
Scaffolds Containing Terminal Hydrogen-Bonding Recognition Motifs at
Each Repeating Unit
Ludger P. Stubbs and Marcus Weck*[a]
Abstract: Polymers containing terminal
hydrogen-bonding recognition motifs
based on diaminotriazine and diamino-
pyridine groups in their side chains for
the self-assembly of appropriate recep-
tors have been prepared by ring-opening
metathesis polymerization (ROMP) of
norbornenes. A new synthetic method
for the preparation of norbornene mon-
omers based on pure alkyl spacers is
introduced. These monomers show un-
precedented high reactivity using
ROMP. To suppress self-association of
diaminotriazine-based polymers, poly-
merizations were run in presence of N-
butylthymine. The butylthymine acts as
a protecting group via self-assembly
onto the hydrogen-bonding sites of the
polymeric scaffold, thereby solubilizing
the polymer. Diaminopyridine mono-
mers do not require the presence of a
protecting group due to their low pro-
pensity to dimerize. In addition, they
exhibit a high affinity for hydrogen-
bonded receptors on both monomeric
and polymeric level. These polymers
present our first building blocks towards
the design and synthesis of a ™universal
polymer scaffold∫.
Keywords: hydrogen bonds ¥ meta-
thesis ¥ receptors ¥ self-assembly
crystalline polymers.[2] Other approaches include the design of
polymers with switchable phase transitions by self-assembly
of alkylphenol side-chains to a polyvinylpyridine backbone[3]
and the self-assembly of biological receptors and small
molecules such as electroactive guests on partially diamino-
triazine-substituted polystyrenes.[4]
A major disadvantage with many current side-chain func-
tionalized polymer systems based on hydrogen bonding is the
lackof recognition motif density, or the lackof stability of the
hydrogen bond due to the use of only a single hydrogen bond
per side-chain. To overcome these shortcomings, we decided
to base our methodology on diaminotriazine- and diamino-
pyridine units. It has been shown that efficient hydrogen-
bonding to receptors by donor acceptor donor interactions
can be achieved by incorporation of these recognition units
into the polymer backbone.[5, 6]
Introduction
The design of supramolecular structures and self-healing
materials based on the self-assembly of smaller subunits is
desirable due to the parallel nature of the self-assembly step.[1]
On the macromolecular scale, the self-assembly of molecules
to corresponding recognition units of a polymer strand is the
basis of DNA replication and the biosynthesis of proteins.
Inspired by nature×s efficiency in creating complex materials
on the basis of a small number of building blocks by self-
assembly, we are developing a new methodology in polymer
science by designing and synthesizing polymer backbones
with multiple recognition sites in their side chains that can be
functionalized via non covalent interactions, such as hydrogen
bonding, ionic forces, or metal coordination (Scheme 1). Such
a ™universal polymer scaffold∫ could allow for the rapid and
reversible functionalization with suitable receptors to create
materials for a wide range of applications in electronics,
sensoring, or biochemical engineering.
Complete control of the polymer architecture, ranging from
statistical- to blockcopolymerization, is desirable to precisely
define the material properties. Ring-opening metathesis
polymerization (ROMP) initiated by ruthenium catalysts
has proven to be an excellent method for the preparation of
complex polymer architectures due to its compatibility with
most functional groups and the possibility to be living, a
Hydrogen bonding by way of acid base interactions has
been utilized in the last decade to self-assemble mesogens to
polymer backbones for the preparation of side-chain liquid
[7]
[a] Prof. Dr. M. Weck, Dr. L. P. Stubbs
School of Chemistry and Biochemistry
Georgia Institute of Technology
Atlanta, GA (USA) 30332-0400
Fax : (‡1)404-894-7452
necessary prerequisite for blockcopolymers. In this paper
we report the design, synthesis, and polymerization of
diaminotriazine- and diaminopyridine-functionalized norbor-
nenes as part of an approach towards a ™universal polymer
scaffold∫.
E-mail: marcus.weck@chemistry.gatech.edu
992
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0992 $ 20.00+.50/0
Chem. Eur. J. 2003, 9, No. 4

992 999
Scheme 1. Schematic representation of the design of a ™universal polymeric scaffold∫. Monomers are polymerized in a controlled fashion to yield well-
defined copolymers (schematic representation of a diblockcopolymer shown) that can be functionalized through an orthogonal self-assembly method ology
to yield highly functionalized copolymers in one simple step. The same polymer can be used for a variety of applications.
coupling of bromomethylnorbornene 6 with the correspond-
ing w-bromo functionalized compounds. Nitriles 1c, d, ester
4b, and bromoalkyl-norbornene 8 were prepared in 66 89%
yields (Scheme 3). The endo/exo-isomer ratios are 1:1 for 3a
and 4:1 for all other monomers.
Results and Discussion
Monomer synthesis: A series of monomers with varying alkyl
spacers [(CH2)n with n ˆ 0,1,5,6], amine substitutions (aryl,
acyl), and heterocycles (triazine, pyridine) were synthesized
to study the influence of the nature and the proximity of the
heterocyclic functionality on the polymerization and self-
assembly behavior.
a
b
All diaminotriazines were prepared by condensation of the
corresponding nitriles with dicyanodiamide[8] and subsequent
acylation. Mono-aryl-substituted substitutions were achieved
by condensation of carboxylic esters with p-tolylbiguanide[9]
(Scheme 2). Triazine ring formations take place under strong-
ly basic conditions. Therefore, the absence of any hydro-
lyzable functional groups other than the nitrile or esters in the
starting materials is mandatory.
CH2Br
CH2MgBr
(CH2)6R
1d: R = CN
4b: R = CO2CH3
6
7
b
c
(CH2)5Br
(CH2)5CN
8
1c
Whereas the preparation of short alkyl spacer nitriles 1a,b
and ester 4a is documented in the literature,[10] we had to
devise a synthetic route to norbornene compounds with long
alkyl spacers and terminal functional groups. This new class of
monomers is accessible by a copper-catalyzed Grignard
Scheme 3. Synthesis of monomer precursors with long alkyl spacers.
a) Mg, THF, 258C, 95%. b) 2 mol% Li2CuCl4, THF, À10 to 258C, 1d:
6-bromohexanenitrile, 71% 4b: 6-bromomethylhexanoate, 89%, 8: 1,4-
dibromobutane, 67%. c) NaCN, DMSO, 808C, 3 h, 90%.
Unsubstituted diaminotriazines 2a d are only soluble in
highly polar solvents such as alcohols or DMSO. However,
after acetylation, monomers 3a, b, and d are highly soluble in
chloroform. Monomer 3c was substituted with isobutyryl
groups to study the influence of bulkier substituents on the
self-assembly properties. The solubility of N-aryl-substituted
monomers 5a and b in chloroform is sufficiently high for the
polymerization and self-assembly experiments.
It is known that in comparison to acylated diaminotriazines,
diaminopyridines show a lower tendency towards dimeriza-
tion and higher association constants with suitable receptors
such as uracils or thymines.[11] These properties would be
beneficial for the proposed application of a polymeric
scaffold. Therefore, we also investigated the synthesis and
self-assembly behavior of diaminopyridine functionalized
norbornenes. Monomers bearing the diaminopyridine motif
were prepared by converting diethyl chelidimate 9 to the
o-benzylated hydrazide 10, followed by conversion to the
azide and Curtius rearrangement to yield 4-benzoxydiamino-
pyridine (11). Acylation with isobutyl chloride and subse-
quent deprotection gave phenol 12 that was coupled with
bromoalkyl-norbornene 8 to yield monomer 13. The bulky
O
R
NH
NH2
N
a
b
N
N
N
(CH2)nCN
(CH2)n
(CH2)n
NH2
N
NH
N
O
R
1a: n = 0
2a: n = 0
3a: n = 0, R = CH3
3b: n = 1, R = CH3
3c: n = 5, R = CH(CH3)2
3d: n = 6, R = CH3
1b: n = 1
1c: n = 5
1d: n = 6
2b: n = 1
2c: n = 5
2d: n = 6
NH2
N
c
N
(CH2)nCO2CH3
(CH2)n
N
NH
4a: n = 1
4b: n = 6
5a: n = 1
5b: n = 6
Scheme 2. Synthesis of diaminotriazine monomers 3a
d and 5a b.
a) Dicyanodiamide, KOH, n-propanol, reflux, 12 h, 57 70%. b) Acetic
anhydride, pyridine, 1208C, 1 h, 27 65% (3a, b, d); isobutyryl chloride,
pyridine, 908C, 2 h, 70% (3c). c) p-Tolylbiguanide, MeOH, NaOCH3,
908C, 96 h, 41 45%.
Chem. Eur. J. 2003, 9, No. 4
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0993 $ 20.00+.50/0
993

M. Weckand L. P. Stubbs
FULL PAPER
isobutyl substituents were chosen to further decrease the
possibility of dimerization. In order to compare the polymer-
ization properties of monomers with pure alkyl-chain spacers
and the more commonly employed spacers based on norbor-
nene-2-carboxylic esters, we synthesized compound 15 from
norbornene acid chloride 14 and bromoundecanol and
coupled it with phenol 12 to give monomer 16 in 65% yield
(Scheme 4).
by 1H NMR spectroscopy. Under these conditions, monomers
3a, b, and 5a, containing short spacer groups, showed no
conversion with catalyst 17 over prolonged periods of time
(96 h). Raising the temperatures to 458C or switching to
CD2Cl2 as a solvent did not increase conversion. Apparently,
the close proximity of the bulky triazine unit to the olefin
severely constrains the reactivity of these monomers. We
therefore switched to catalyst 18 which is known to be
significantly more active in ROMP and ring-closing meta-
thesis than 17.[7, 12] Using catalyst 18, monomer 1a still showed
less than 10% conversion within 24 h, whereas monomers 3a
and 5a showed approximately 40% conversion.
In contrast to the short spacer monomers, compounds 3c, d,
5b, and 13, containing at least a four carbon spacer, proved to
be exceptionally reactive. In all cases, polymerizations ini-
tiated with catalyst 17 were completed in less than two
minutes with monomer to catalyst ratios up to 200:1. This
remarkable reactivity can be attributed to two factors: 1) The
removal of the heterocyclic unit from the proximity of the
olefin limits steric interference, as is evident in the increasing
reactivity of the series 1a < 1b ꢀ 1c, d, and 4a ꢀ 4b. 2) The
absence of any functional group in the spacer dramatically
increases reactivity. Under the same reaction conditions
(monomer to catalyst ratio 50:1, CDCl3, 258C), monomer 13
with a pure alkyl spacer polymerized completely within two
minutes, whereas monomer 16 containing an ester group in
the 2-position of the norbornene tookmore than 24 h to go to
completion. These results suggest that the ester carbonyl
oxygen in the predominant endo isomer retards the reaction
by interfering with the catalyst either by chelation or steric
constraint.
OBn
N
O
a, b
H3N2
N2H3
EtO
OEt
N
H
O
O
O
O
9
10
OH
OBn
O
O
f, g
c, d, e
N
H
N
N
H
H2N
N
NH2
11
12
NH
O
h
N
NH
(CH2)5O
O
13
i
O(CH2)11Br
Cl
O
O
14
15
NMR and GPC data indicate that the rate of propagation
for monomers with pure alkyl spacers is higher than the rate
of initiation of the catalyst, suggesting a non-living behavior.
NH
O
N
1
k
In H NMR spectra of a 10:1 monomer 13 to catalyst 17
NH
mixture, the signal at d ˆ 19.97 ppm of the catalyst carbene
was present even after complete conversion. In contrast,
polymerization of 16 resulted in full conversion of the non-
iniated carbene to a new signal at d ˆ 18.5 ppm; this indicates
full initiation of the catalyst and a living character of the
polymerization. The non-living character of the polymeriza-
tion of pure alkyl spacer monomers leads to broad molecular
weight distributions with polydispersities higher than 1.4
(Table 1). To exclude the possibility that hydrogen-bonding is
responsible for the broad molecular weight distributions,
polymers of ester 4b were prepared and found to have high
polydispersities as well (PDI >2).
O(CH2)11
O
O
O
16
Scheme 4. Synthesis of diaminopyridine monomers 13 and 15. a) BzBr,
K2CO3, DMF, 808C, 4 h, 78 %. b) N2H4, EtOH, reflux, 12 h, 92%.
c) NaNO2, HCl, 08C, 20 min. d) EtOH, reflux, 12 h. e) EtOH/KOH (aq.),
reflux, 18 h, 49% (overall). f) isobutyryl chloride, NEt3, DCM, 258C, 86%.
g) H2, Pd/C, EtOH, 100%. h) 8, K2CO3, DMSO, 908C, 4 h, 83%.
i) Bromoundecanol, pyridine, THF, reflux, 2 h, 91%. k) 12, K2CO3, DMSO,
908C, 4 h, 65%.
Polymer synthesis: The polymerizations were performed
using ruthenium initiators 17 and 18.
Mes
Cl
Cl
N
N
Mes
Ph
Table 1. GPC data for selected polymers.[a]
PCy3
Ru
Cl
Cl
Cy=Cyclohexyl
Mes=Mesityl
[M]/[C][b]
Mn
Mw (theor)
PDI[c]
Ru
Monomer
Ph
PCy3
PCy3
3c
3d
4b
5b
13
50
45
50
50
75
12095
8665
14737
12128
22700
20700
16740
11800
18875
32047
1.43
1.48
2.02
1.67
1.75
17
18
The polymerizations were carried out using 0.2m solutions
of the monomers in deuterated chloroform at ambient
temperatures with monomer to catalyst ratios of 20:1
200:1. The progress of the polymerizations was monitored
[a] Eluent: THF [b] Monomer to catalyst ratio. [c] Polydispersity index.
Reaction conditions: CDCl3, 20 min. Conversion was quantitative by NMR
for all monomers.
994
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0994 $ 20.00+.50/0
Chem. Eur. J. 2003, 9, No. 4

Universal Polymer Backbone
992 999
The diaminotriazine polymers immediately precipitated
from solution following addition of the catalyst due to self-
association. Wheras Rotello et al. have observed micellar-like
folding into compact globules for polystyrenes that are
partially functionalized with diaminotriazine units,[13] the
much higher density of hydrogen-bonding units in our
polymers renders them insoluble in solvents of low polarity.
However, the precipitated polymers could be solubilized by
heating and ultrasonification in the presence of N-butylth-
ymine, which acts as a chloroform-soluble receptor for the
diaminotriazine units and competes with the inter- and
intramolecular self-association of the polymer chains by
forming a triple hydrogen-bond interaction (Scheme 5).
To overcome the problem of precipitation, we carried out
the polymerizations of diaminotriazine monomers 3a d and
5a b in the presence of butylthymine (1 3 equivalents). The
competitive self-assembly of the butylthymine to the recog-
nition units during polymerization suppresses dimerization,
and the solutions remained homogeneous. In analogy to
organic chemistry, the butylthymine can be regarded as a
protecting group for the diaminotriazine units. As a general
strategy, it might be possible to carry out the synthesis of self-
assembled diaminotriazine polymers by preforming a com-
plex between monomer and receptor, utilizing the receptor as
both a protecting group and a functionalization agent for the
diaminotriazine units. However, this requires that the recep-
tor does not interact with the polymerization catalyst.
Whereas excess butylthymine did not affect the catalyst, this
is not necessarily the case for highly functionalized receptors,
and the method of self-assembly prior to polymerization is
inferior to using a polymer backbone that does not show self-
association behavior. Therefore, diaminopyridine monomers
are clearly preferred to their diaminotriazine counterparts.
CH3
O
R
R
N
H
N
R
N
H
N
P
N
N
N
N
N
N
N
N
N
H
H
H
But
a
N
H
N
R
O
H
N
R
N
R
P
P
insoluble
soluble
polymer backbone
P
Self-assembly studies: To further quantify the self-association,
dimerization constants for monomers 3c, 3d, 5b, 13, N-
butylthymine, and poly-13 were determined by measuring the
1H NMR chemical shift of the amide protons as a function of
concentration in chloroform solutions[15] (Figure 1, Table 2).
Scheme 5. Reversible cross-linking of polymers by hydrogen bonds.
a) 1-Butylthymine (excess), heat, ultrasound.
N-Acetyl diaminotriazines 3a, b, and 3d showed the
strongest dimerization of all monomers. Polymers based on
these compounds require at least three equivalents of
butylthymine to dissolve, whereas one equivalent is sufficient
for polymers based on N-isobutyryl substituted 3c. These
observations can be rationalized by assuming that acetylated
diaminotriazines dimerize by quadruple hydrogen bonds in
their favored cis conformation,[11] whereas steric interaction of
the isobutyryl groups with the triazine ring possibly favors the
trans conformation in 3c,[14] with only two hydrogen bonds in
the dimer that are weakened by steric repulsion (Scheme 6).
R
R
O
N
N
O
N
N
N
H
N
N
H
O
N
H
N
N
H
O
H
N
H
N
H
N
H
N
O
N
O
N
N
N
O
N
N
O
R
R
Scheme 6. Quadruple hydrogen bond of N-acetyl-diaminotriazines versus
double hydrogen bond of N-isobutyryl-diaminotriazines in their preferred
conformations.
Figure 1. Chemical shifts of the amide protons of 3c, 3d, poly-13, 13, and
the p-tolylamino proton of 5b as a function of the concentration in CDCl3.
Table 2. Dimerization and association constants determined by 1H NMR
data.[a]
Polymers based on N-aryl substituted monomers 5a and 5b
also precipitated from solution, which was not to be expected
from their low dimerization constant (see self-assembly
experiments). Probably additional hydrogen bonds are
[b]
[b, c]
Compound
Kdim [mÀ1
]
Ka [mÀ1
]
3c
45 (Æ5)
3d
93 (Æ15)
formed in the polymer networkbetween NH protons and
2
5b[d]
2.6 (Æ0.2)
4.1 (Æ0.2)
0.31 (Æ0.15)
nitrogen atoms of the triazine rings. In contrast, diaminopyr-
idine-based monomers 13 and 16 were polymerized without
any precipitation or gelation. The low propensity of these
monomers to self-associate allows for a homogeneous poly-
merization despite the high density of recognition units
tethered to the backbone.
N-butylthymine
13
poly-13
116 (Æ11)
73 (Æ9)
< 5
[a] Binding constants were calculated by curve fitting with the computer
program ChemEquili.[16] [b] Measured in CDCl3 at 228C. [c] With receptor
N-butylthymine. [d] Calculated for p-tolyl-NH.
Chem. Eur. J. 2003, 9, No. 4
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0995 $ 20.00+.50/0
995

M. Weckand L. P. Stubbs
FULL PAPER
With the exception of monoarylated diaminotriazine 5b, the
values reflect the polymerization properties of the com-
pounds, with the highest constant measured for the N-acyl
diaminotrazine 3d and negligible self-association observed
for diaminopyridine 13. The dimerization constant of poly-13
could only be determined with a wider error range due to
peakbroadening of the amide protons, but is small with a Kdim
of less than 5molÀ1.
For an efficient self-assembly of receptors to the polymeric
scaffold, it is mandatory that the binding constants of the
monomers do not significantly change after polymerization.
We therefore compared the association constants of monomer
13 and poly-13. The binding constants were determined by
NMR titrations, using N-butylthymine as a model receptor
(Figure 2). As shown in Table 2, the difference in binding
strength is small and more likely due to limited accessibility of
binding sites in the polymer than to competitive self-
association. The binding constant of 116mÀ1 is in the lower
range of typical values for diaminopyridines, but switching to
linear acyl substituents has the potential to increase the
binding strength[11] and allow for improved self-assembly of
receptors.
limiting their use. In self-assembly studies and polymerization
experiments, we found that diaminopyridines are superior to
diaminotriazines due to their high binding constants to
receptors and their low self-association, eliminating the
necessity to preform a monomer receptor complex before
polymerization.
The presented methodology of the synthesis of polymers
containing hydrogen-bonding units and their functionaliza-
tion based on self-assembly has a number of advantages over
previously reported systems, including 1) high recognition
motif density, 2) controllable polymerization behavior, and
3) low dimerization and high association constants of the
recognition units towards hydrogen bonding based on a
donor acceptor donor motif. With an optimized hydrogen-
bonding polymer backbone in hand, research on the self-
assembly of a suitable receptors for selected applications in
materials science is in progress.
Experimental Section
General methods: All reactions were carried out under an argon
atmosphere in oven-dried glassware. Anhydrous THF and dichlorome-
thane were purchased from Aldrich and passed over columns of activated
alumina under argon to remove traces of water. Deuterated chloroform
used for polymerization experiments was distilled over calcium hydride and
stored in the darkunder argon. All other solvents and commercially
available reagents were used without further purification. Ruthenium
compounds were bought from Strem Chemicals, Inc. Flash-column
chromatography was carried out on silica gel 60, 230 400 mesh (What-
man). Gel-permeation chromatography (GPC) was carried out on polymer
solutions in THF at 308C (column combination: 2x American Polymer
Standards 10 m particle size, linear mixed bed packing, flow rate
1 mLminÀ1) with a Waters 1525 binary pump coupled to a Waters 2414
refractive index detector. Calibrations are based on polystyrene standards.
NMR spectra were recorded on a Varian Mercury 300 spectrometer (1H:
300 MHz, 13C: 75 MHz). Chemical shifts are reported in ppm on the d scale
relative to the solvent signal. Electrospray ionization (ESI) mass spectra
were obtained on a Micromass Quattro LC spectrometer, and fast atom
bombardment (FAB) mass spectra on a VG Instruments 70SE spectrom-
eter. Elemental analyses were performed by Atlantic Microlabs, Norcross,
GA. The following compounds were prepared according to literature
procedures: 6-bromohexanitrile,[17] 6-bromohexanoic acid methyl ester,[18]
5-bromomethylnorbornene (6),[10] norbornene-2-carbonitrile (1a),[10] nor-
bornene-2-yl-acetonitrile (1b),[19] norbornene-2-yl-acetic methyl ester
(4a),[19] norbornene-2-carboxylic 11-bromoundecyl ester (14).[20] 4-Oxo-
1,4-dihydropyridine-2,6-diethylcarboxylate[21] (9) was prepared by esterifi-
cation of chelidamic acid.[22]
Figure 2. Chemical shifts of 1-butylthymine upon titration with monomer
13 and poly-13 (60-mer). Equivalents for poly-13 are based on monomer
molecular weight.
p-Tolylbiguanide: p-Toluidine hydrochloride (4.28 g, 0.030 mol) and dicya-
nodiamide (2.48 g, 0.029 mol) were heated under reflux in water (100 mL)
for 12 h. On cooling, p-tolylbiguanidinium hydrochloride crystallized from
the solution. The hydrochloride was heated under reflux with sodium
hydroxide (4.0 g) in 50% aqueous ethanol (100 mL) for 1 h. The ethanol
was evaporated and the precipitated product washed with water. Recrys-
tallization from ethanol yielded white crystals (3.65 g, 66%). 1H NMR
([D6]DMSO): d ˆ 7.5 6.0 (br, 4H, NH), 7.00 (d, J ˆ 7.7 Hz, 2H), 6.70 (d,
J ˆ 7.7 Hz, 2H), 4.5 (brs, 2H, NH), 2.20 (s, 3H); 13C NMR ([D6]DMSO):
d ˆ 160.2, 158.6, 148.4, 130.2, 130.0, 123.4, 21.1; MS (ESI): m/z: calcd for:
Conclusion
To develop a methodology based on a ™universal polymeric
scaffold∫, we investigated the synthesis, polymerization, and
self-assembly properties of diaminotriazine- and diaminopyr-
idine-functionalized norbornenes. A strong effect of the alkyl
spacer length on the reactivity of the monomers was observed,
with monomers having long alkyl spacers and no functional
group in the chain being exceptionally reactive. It is remark-
able that the ring-opening metathesis polymerizations of
these monomers, which are based on functional groups
containing aromatic nitrogens, proceeds without decomposi-
tion of the catalyst. It is well known that nitrogen containing
compounds deactivate ruthenium catalyst 17 in other olefin
metathesis reactions such as ring-closing metathesis, thereby
‡
191.2; found: 191.7 [M ]; elemental analysis calcd (%) for C9H13N5: C
56.53, H 6.85, N 36.62; found: C 56.46, H 6.73, N 36.38.
N-Butylthymine: Thymine (10.0 g, 0.079 mol), bromobutane (3.62 g,
0.026 mol) and potassium carbonate (11.0 g, 0.08 mol) were stirred in
DMSO (200 mL) at 508C for 8 h. The suspension was filtered, the filter
cake washed with dichloromethane, and the filtrate concentrated in vacuo.
The solid residue was treated with water (300 mL) and extracted with
dichloromethane (3 Â 200 mL). The organic phases were dried and the
solvent removed. Purification of the remaining solid by column chroma-
996
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0996 $ 20.00+.50/0
Chem. Eur. J. 2003, 9, No. 4

Universal Polymer Backbone
992 999
tography (hexanes/ethyl acetate 1:2) and recrystallization from chloroform/
hexanes yielded the title compound as white crystals (2.70 g, 57%).
1H NMR (CDCl3): d ˆ 9.40 (brs, 1H, NH), 6.96 (d, J ˆ 1 Hz, 1H), 3.68 (t,
J ˆ 7.1 Hz, 2H), 1,90 (d, J ˆ 6.9 Hz, 3H), 1.64 (m, 2H), 1.33 (m, 2H), 0.93 (t,
J ˆ 7.3 Hz, 3H); 13C NMR (CDCl3): d ˆ 165.0, 151.4, 140.7, 110.7, 48.4, 31.3,
3.50 1.00 (m, 7H); 13C NMR ([D6]DMSO) (endo ‡ exo): d ˆ 180.8, 179.7,
167.6, 167.4, 138.5, 137.4, 137.1, 133.8, 49.8, 48.1, 46.8, 46.5, 46.2, 42.7, 42.0,
‡
30.8, 29.7; MS (ESI): m/z: calcd for: 203.2; found: 203.8 [M ]; elemental
analysis calcd (%) for C10H13N5: C 59.10, H 6.45, N 34.46; found: C 58.78, H
6.48, N 34.64.
‡
19.9, 13.9, 12.5; MS (FAB): m/z: calcd for: 182.1; found: 182.1 [M ];
6-Norbornenyl-methyl-2,4-diamino-[1,3,5]-triazine (2b): Prepared from 1b
(4.66 g, 0.035 mol) to yield white crystals (5.31 g, 70%). 1H NMR
([D6]DMSO): d ˆ 6.55 (brs, 4H, NH), 6.15 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz,
1Hendo), 6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 3.50 0.50 (m, 9H); 13C NMR
([D6]DMSO) (endo isomer): d ˆ 177.9, 167.7, 137.5, 133.4, 49.7, 45.9, 43.6,
elemental analysis calcd (%) for C9H14N2O2: C 59.32, H 7.74, N 15.37;
found: C 59.04, H 7.77, N 15.19.
General procedure for the Grignard coupling reaction: 5-Bromomethyl-
norbornene (6; 8.84 g, 0.047 mol) was slowly added to magnesium turnings
(1.30 g, 0.054 mol) in anhydrous THF (50 mL). After stirring for 24 h at
ambient temperatures, the Grignard solution was isolated from residual
magnesium (conversion: 90 95%) and slowly added at À108C to a
solution of the w-bromoalkane (0.040 mol) and Li2CuCl4 (0.1m in THF,
5 mL) in anhydrous THF (30 mL). The reaction mixture was allowed to
warm to ambient temperatures within 18 h. Diethyl ether (100 mL) was
added and the solution washed with saturated aqueous NH4Cl (50 mL).
The aqueous phase was extracted with diethyl ether (100 mL) and the
combined organic phases were washed with brine (100 mL) and dried over
magnesium sulfate. The solvents were removed under vacuum and the
residue purified by column chromatography or distillation.
‡
42.7, 37.2, 31.9; MS (ESI): m/z: calcd for: 217.3; found: 217.9 [M ];
elemental analysis calcd (%) for C11H15N5: C 60.81, H 6.96, N 32.23; found:
C 60.52, H 6.69, N 32.58.
6-(5-Norbornenyl-pentyl)-2,4-diamino-[1,3,5]-triazine (2c): Prepared from
1c (3.20 g, 0.016 mol) to yield a white solid (2.94 g, 67%). 1H NMR
([D6]DMSO): d ˆ 6.52 (brs, 4H, NH), 6.10 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz,
1Hendo), 6.05 (m, 2Hexo), 5.90 (dd, 1Hendo), 2.70 (m, 2H), 2.45 (t, J ˆ
7.1 Hz, 2H), 2.40 0.20 (m, 15H); 13C NMR ([D6]DMSO) (endo isomer):
d ˆ 178.5, 167.7, 137.4, 133.0, 49.8, 45.5, 42.6, 38.8, 38.7, 34.9, 32.7, 29.8, 28.6,
‡
27.8; MS (FAB): m/z: calcd for: 273.4; found: 274.1 [M ‡H]; elemental
analysis calcd (%) for C16H25N5: C 65.90, H 8.48, N 25.62; found: C 65.81, H
8.46, N 25.78.
7-Norbornenyl-heptanenitrile (1d): Prepared from 6 (8.84 g, 0.047 mol)
and 6-bromohexanitrile (7.10 g, 0.040 mol). Purification by column chro-
matography on silica gel (dichloromethane/hexanes 1:1) gave 1d as a light
yellow oil (5.48 g, 71%). 1H NMR (CDCl3): d ˆ 6.12 (dd, J1 ˆ 5.5, J2 ˆ
2.7 Hz, 1Hendo), 6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 2.72 (brs, 2H), 2.31 (t,
J ˆ 7.1 Hz, 2H), 2.00 0.40 (m, 15H); 13C NMR (CDCl3) (endo isomer):
d ˆ 137.1, 132.5, 120.1, 49.8, 45.6, 42.7, 38.9, 34.8, 32.6, 29.2, 28.8, 28.5, 25.6,
6-(6-Norbornenyl-hexyl)-2,4-diamino-[1,3,5]-triazine (2d): Prepared from
1d (7.09 g, 0.035 mol) to yield a white solid (5.75 g, 57%). 1H NMR
([D6]DMSO): d ˆ 6.55 (brs, 4H, NH), 6.15 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz,
1Hendo), 6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 2.70 (m, 2H), 2.25 (t, J ˆ
7.1 Hz, 2H), 2.40 0.20 (m, 15H); 13C NMR ([D6]DMSO) (endo isomer):
d ˆ 178.4, 167.7, 137.4, 133.0, 49.8, 45.6, 42.6, 42.7, 39.1, 39.0, 34.9, 32.6, 29.8,
‡
17.3; MS (ESI): m/z: calcd for: 203.2; found: 203.2 [M ]; elemental analysis
‡
28.7, 27.2; MS (ESI): m/z: calcd for: 287.4; found: 288.1 [M ]; elemental
calcd (%) for C14H21N: C 82.70, H 10.41, N 6.89; found: C 82.54, H 10.61, N
6.79.
analysis calcd (%) for C16H25N5: C 66.86, H 8.77, N 24.37; found: 66.76, H
9.03, N 23.77.
7-Norbornenyl-heptanoic acid methyl ester (4b): Prepared from 6 (6.54 g,
0.035 mol) and 6-bromohexanoic acid methyl ester (4.81 g, 0.023 mol).
Purification by column chromatography on silica gel (dichloromethane)
gave 4b as a light yellow oil (4.89 g, 89%). 1H NMR (CDCl3): d ˆ 6.12 (dd,
J1 ˆ 5.5, J2 ˆ 2.7 Hz, 1Hendo), 6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 3.63 (s, 3H),
2.70 (brs, 2H), 2.26 (t, J ˆ 7.7 Hz, 2H), 2.00 0.40 (m, 15H); 13C NMR
(CDCl3) (endo isomer): d ˆ 174.5, 137.1, 132.6, 51.6, 49.7, 45.6, 42.7, 38.9,
34.9, 34.3, 32.6, 29.7, 29.4, 28.6, 25.1; MS (ESI): m/z: calcd for: 236.2; found:
6-Norbornenyl-2,4-bis(acetylamino)-[1,3,5]-triazine (3a): Compound 2a
(2.95 g, 0.0145 mol) was heated with acetic anhydride (12.50 g, 0.12 mol) to
1408C until the solution became clear. Upon cooling, 3a precipitated and
was purified by column chromatography (ethyl acetate) to give off-white
crystals (2.71 g, 65%). 1H NMR (CDCl3): d ˆ 9.96 (brs, 1H, NH), 9.92 (brs,
1H, NH), 6.15 (m, 2Hendo), 6.05 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz, 1Hendo), 5.78 (dd,
1Hexo), 2.58 (s, 6H, CH3), 3.50 1.20 (m, 7H); 13C NMR (CDCl3) (endo ‡
exo isomers): d ˆ 184.9, 183.6, 173.5, 173.2, 163.9, 163.7, 138.6, 137.9, 136.7,
132.6, 50.2, 48.5, 48.4, 47.9, 47.7, 46.1, 43.1, 42.4, 31.9, 30.2, 26.5; MS (ESI):
‡
237.0 [M ]; elemental analysis calcd (%) for C15H24O2: C 76.23, H 10.24;
found: C 76.07, H 10.41.
‡
m/z: calcd for: 288.1; found: 288.1 [M ‡H]; elemental analysis calcd (%)
5-(5-Bromopentyl)-norbornene (8): Prepared from 5-bromomethylnorbor-
nene (8.84 g, 0.047 mol) and 1,4-dibromobutane (50 g, 0.24 mol). Distil-
lation yielded 8 as a colorless liquid (b.p. 90–948C, 0.1 mbar) in 67% yield.
The product is approx. 95% pure (GC) and was used without further
for C14H17N5O2: C 58.52, H 5.96, N 24.38; found: C 58.15, H 5.84, N 24.38.
6-Norbornenyl-methyl-2,4-bis(acetylamino)-[1,3,5]-triazine (3b): Com-
pound 3b was prepared in analogy to above using 2b (3.25 g, 0.015 mol)
and acetic anhydride (12.50 g, 0.12 mol). Purification by column chroma-
tography (ethyl acetate) yielded a white solid (1.96 g, 45%). 1H NMR
(CDCl3): d ˆ 9.50 (brs, 2H, NH), 6.15 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz, 1Hendo), 6.05
(m, 2Hexo), 6.02 (dd, 1Hendo), 2.47 (s, 6H, CH3), 2.80 0.60 (m, 9H);
13C NMR (CDCl3) (endo isomer): d ˆ 181.7, 173.1, 164.0, 137.8, 132.6, 49.6,
45.9, 44.1, 42.8, 37.2, 32.3, 26.4; MS (ESI): m/z: calcd for: 302.1; found: 302.1
1
purification. H NMR (CDCl3): d ˆ 6.12 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz, 1Hendo),
6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 3.40 (t, J ˆ 6.9 Hz, 2H), 2.75 (brs, 2H),
2.00 0.50 (m, 13H); 13C NMR (CDCl3) (endo isomer): d ˆ 137.2, 132.5,
45.6, 42.7, 38.9, 36.6, 34.8, 34.3, 33.1, 32.6, 28.6, 28.0.
7-Norbornenyl-hexanenenitrile (1c): Compound 8 (3.60 g, 0.014 mol) and
finely powdered sodium cyanide (1.00 g, 0.020 mol) were stirred in DMSO
(100 mL) at 808 C for 3 h. Water (100 mL) was added and the solution
extracted with diethyl ether (2 Â 200 mL). The extracts were washed with
water and 5% hydrochloric acid (100 mL). The solvent was removed and
the residue purified by column chromatography (hexanes/dichloromethane
1:1) to afford 1c as a colorless oil (2.90 g, 90%). 1H NMR (CDCl3): d ˆ 6.12
(dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz, 1Hendo), 6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 2.72
(brs, 2H), 2.31 (t, J ˆ 7.1 Hz, 2H), 2.00 0.40 (m, 13H); 13C NMR (CDCl3)
(endo isomer): d ˆ 137.1, 132.5, 120.1, 49.8, 45.6, 42.7, 38.8, 34.6, 32.6, 29.1,
‡
[M ‡H]; elemental analysis calcd (%) for C15H19N5O2: C 59.79, H 6.36, N
23.24; found: C 59.32, H 6.36, N 22.73.
6-(6-Norbornenyl-hexyl)-2,4-bis(isobutyrylamino)-[1,3,5]-triazine
(3c):
Isobutyryl chloride (1.2 mL) was added to a solution of 2c (1.26 g,
4.6 mmol) in pyridine (30 mL) and the reaction mixture stirred at 908C
for 2 h. Evaporation of volatiles and chromatographic purification of the
residue (ethyl acetate/hexanes 1:1) yielded 3c as a slightly yellow sticky
solid (1.34 g, 70%). 1H NMR (CDCl3): d ˆ 9.10 (brs, 2H, NH), 6.15 (dd,
J1 ˆ 5.5, J2 ˆ 2.7 Hz, 1Hendo), 6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 2.70 (m,
2H), 2.57 (s, 6H, CH3), 2.40 0.20 (m, 15H); 13C NMR (CDCl3) (endo
isomer): d ˆ 182.2, 173.1, 164.0, 137.1, 132.6, 49.7, 45.6, 42.7, 39.1, 39.0, 34.9,
32.6, 29.8, 29.4, 28.7, 27.2, 26.4; MS (ESI): m/z: calcd for: 413.6; found: 414.1
‡
28.0, 25.6, 17.3; MS (ESI): m/z: calcd for: 189.3; found: 189.9 [M ];
elemental analysis calcd (%) for C14H21N: C 82.48, H 10.12, N 7.40; found:
C 82.42, H 10.13, N 7.46.
‡
General procedure for the preparation of diaminotriazines: Dicyanodia-
mide (4.20 g, 0.050 mol), potassium hydroxyde (1.0 g) and the norborne-
nylnitrile (0.035 mol) were stirred in anhydrous n-propanol (50 mL) at
reflux for 12 h. The solvent was removed, the residue washed with hot
water, dried, and recrystallized from ethanol.
[M ]; elemental analysis calcd (%) for C23H35N5O2: C 66.80, H 8.53, N
16.93; found: C 65.61, H 8.69, N 15.51.
6-(6-Norbornenyl-hexyl)-2,4-bis(acetylamino)-[1,3,5]-triazine (3d): Acetic
anhydride (6 mL) was added to a solution of 2d (0.94 g, 3.1 mmol) in
pyridine (25 mL) and the reaction mixture stirred at 1208C for 12 h.
Evaporation of volatiles and chromatographic purification of the residue
(ethyl acetate) yielded 3d as a white solid (0.31 g, 27%). 1H NMR (CDCl3):
d ˆ 9.10 (brs, 2H, NH), 6.15 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz, 1Hendo), 6.05 (m,
6-Norbornenyl-2,4-diamino-[1,3,5]-triazine (2a): Prepared from 1a (4.16 g,
0.035 mol) to yield white crystals (4.68 g, 65%). 1H NMR ([D6]DMSO):
d ˆ 6.80 (brs, 4H, NH), 6.15 (m, 2Hendo), 6.05 (m, 1Hexo), 5.78 (m, 1Hexo),
Chem. Eur. J. 2003, 9, No. 4
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0997 $ 20.00+.50/0
997

M. Weckand L. P. Stubbs
FULL PAPER
2Hexo), 5.95 (dd, 1Hendo), 2.70 (m, 2H), 2.57 (s, 6H, CH3), 2.40 0.20 (m,
15H); 13C NMR (CDCl3) (endo isomer): d ˆ 182.2, 173.1, 164.0, 137.1, 132.6,
49.7, 45.6, 42.7, 39.1, 39.0, 34.9, 32.6, 29.8, 29.4, 28.7, 27.2, 26.4; MS (ESI):
m/z: calcd for: 371.5; found: 372.0 [M ]; elemental analysis calcd (%) for
C20H29N5O2: C 64.66, H 7.87, N 18.85; found: 64.68, H 8.02, N 18.62.
title compound as a white solid (2.087 g, 86%). 1H NMR (CDCl3): d ˆ 7.70
(brs, 2H, NH), 7.68 (s, 2H, Hpy), 7.45 7.25 (m, 5H), 5.13 (s, 2H, CH2), 2.51
(septet, J ˆ 6.9 Hz, 2H), 1,24 (d, J ˆ 6.9 Hz, 12H); 13C NMR (CDCl3): d ˆ
175.7, 168.9, 150.8, 136.0, 128.8, 128.4, 127.8, 96.7, 70.3, 37.1, 19.6; MS (ESI):
‡
‡
m/z: calcd for: 355.2; found: 356.0 [M ]; elemental analysis calcd (%) for
C20H25N3O3: C 67.58, H 7.09, N 11.82; found: C 66.98, H 7.12, N 11.36.
6-Norbornenyl-methyl-2-(N-(p-tolyl))-amino-4-amino-[1,3,5]-triazine
(5a): In a pressure bottle, 4a (1.65 g, 0.010 mol), p-tolylbiguanide (1.92 g,
0.010 mol), and sodium methoxide (0.2 g) were stirred at 908C in
anhydrous methanol (40 mL) for 96 h. Evaporation of the solvent and
purification of the residue by column chromatography (hexanes/ethyl
acetate 1:1) gave the title compound as a white solid (1.38 g, 45%).
1H NMR ([D6]DMSO): d ˆ 9.22 (brs, 1H, NH), 7.62 (d, J ˆ 8.2 Hz, 2H),
7.02 (d, J ˆ 8.2 Hz, 2H), 6.82 (brs, 2H, NH2), 6.15 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz,
1Hendo), 6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 2.21 (s, 3H), 2.70 0.50 (m, 9H);
13C NMR ([D6]DMSO) (endo): d ˆ 178.0, 167.4, 164.9, 138.1, 137.5, 133.3,
131.2, 129.5, 120.4, 49.8, 45.9, 43.7, 42.7, 37.3, 32.0, 21.0; MS (ESI): m/z: calcd
4-Hydroxy-2,6-bis(isobutyrylamino)pyridine (12): In a pressure bottle,
4-benzyloxy-2,6-bis(N-isobutyryl)pyridine (0.940 g, 2.64 mmol) was dis-
solved in absolute ethanol (100 mL), 5% palladium on charcoal (300 mg)
was added, and the reaction mixture shaken under hydrogen (3 bar) for 1 h.
The suspension was filtered over Celite and the solvent removed to yield 12
as a white solid (0.700 g, 100%). 1H NMR ([D6]DMSO): d ˆ 9.70 (brs, 2H,
NH), 7.24 (s, 2H, Hpy), 2.70 (septet, J ˆ 6.9 Hz, 2H), 1.05 (d, J ˆ 6.9 Hz,
12H); 13C NMR ([D6]DMSO): d ˆ 175.7, 169.9, 150.8, 96.7, 70.3, 37.1, 19.6;
‡
MS (ESI): m/z: calcd for: 265.1; found: 265.9 [M ].
4-(5-Norbornenylpentyloxy)-2,6-bis(isobutyrylamino)pyridine (13): Com-
‡
for: 307.4; found: 308.1 [M ]; elemental analysis calcd (%) for C18H21N5: C
pound 12 (196 mg
, 0.74 mmol), bromoalkyl-norbornene 8 (190 mg,
70.33, H 6.89, N 22.78; found: 69.79, H 6.90, N 22.79.
0.78 mmol), potassium carbonate (200 mg, 1.44 mmol), and 18-crown-6
(10 mg, 0.04 mmol) were stirred in DMSO (10 mL) at 908C for 3 h. Water
(50 mL) was added and the mixture extracted with diethyl ether.
Purification by column chromatography (hexanes/ethyl acetate 1:1) gave
13 (260 mg, 81%) as a colorless viscous oil that crystallized upon standing.
1H NMR (CDCl3): d ˆ 7.54 (s, 4H, Hpy ‡ NH), 6.12 (dd, J1 ˆ 5.5, J2 ˆ
2.7 Hz, 1Hendo), 6.05 (m, 2Hexo), 5.95 (dd, 1Hendo), 4.00 (t, J ˆ 6.2 Hz, 2H),
2.74 (brs, 2H), 2.49 (septet, J ˆ 6.9 Hz, 2H), 2.0 1.7 (m, 4H), 1.5 1.0 (m,
8H), 1.23 (d, J ˆ 6.9 Hz, 12H), 0.52 0.44 (m, 1H); 13C NMR (CDCl3)
(endo isomer): d ˆ 175.5, 169.1, 150.6, 137.1, 132.6, 96.4, 68.7, 49.9, 45.7, 45.5,
42.8, 38.9, 37.2, 35.0, 32.7, 29.3, 28.6, 26.4, 19.8; MS (ESI): m/z: calcd for:
6-(6-Norbornenyl-hexyl)-2-(N-(p-tolyl))-amino-4-amino-[1,3,5]-triazine
(5b): The title compound was prepared in analogy to above using 4b
(2.36 g, 0.010 mol), p-tolylbiguanide (2.06 g, 0.011 mol), and sodium meth-
oxide (0.2 g). Purification by column chromatography (hexanes/ethyl
acetate 1:1) gave 5b as a white solid (1.54 g, 41%). 1H NMR ([D6]DMSO):
d ˆ 9.30 (brs, 1H, NH), 7.40 (d, J ˆ 8.2 Hz, 2H), 7.12 (d, J ˆ 8.2 Hz, 2H),
6.80 (brs, 2H, NH2), 6.05 (dd, J1 ˆ 5.5, J2 ˆ 2.7 Hz, 1Hendo), 6.05 (m, 2Hexo),
5.90 (dd, 1Hendo), 2.31 (s, 3H), 2.70 0.50 (m, 18H); 13C NMR ([D6]DMSO)
(endo): d ˆ 178.4, 167.4, 164.9, 138.1, 137.3, 133.0, 131.2, 129.4, 120.4, 49.8,
45.5, 42.6, 38.9, 38.7, 35.0, 32.7, 29.9, 29.5, 28.7, 21.1; MS (FAB): m/z: calcd
‡
‡
427.3; found: 428.2 [M ]; elemental analysis calcd (%) for C25H37N3O3: C
70.22, H 8.72, N 9.83; found: C 68.85, H 8.83, N 9.62.
for: 377.5; found: 378.3 [M ‡H]; elemental analysis calcd (%) for
C23H31N5: C 73.17, H 8.28, N 18.55; found: C 72.82, H 8.24, N 18.49.
Norbornene-2-carboxylic 11-(2,6-bisisobutyrylamino-pyridin-4-yloxy) un-
decyl ester (16): Compound 12 (210 mg, 0.79 mmol), bromo-ester 15
(300 mg, 0.80 mmol), and potassium carbonate (400 mg, 2.88 mmol) were
stirred in DMSO (10 mL) at 958C for 5 h. Water (50 mL) was added and
the mixture extracted with diethyl ether. The extracts were washed with
brine, dried, and the solvent removed. Purification by column chromatog-
raphy (hexanes/ethyl acetate 1:1) yielded 15 as a white solid (284 mg,
65%). 1H NMR (CDCl3): d ˆ 8.02 (s, 2H, NH), 7.47 (s, 2H), 6.08 (dd, J1 ˆ
5.5, J2 ˆ 2.7 Hz, 1Hendo), 6.02 (m, 2Hexo), 5.83 (dd, 1Hendo), 3.95 (m, 4H),
3.10 (brs, 1H), 2.86 (m, 1H), 2.79 (brs, 1H), 2.40 (septet, J ˆ 6.9 Hz, 2H),
1.80 1.05 (m, 35H); 13C NMR (CDCl3) (endo isomer): d ˆ 176.0, 175.2,
169.1, 150.9, 137.8, 132.5, 96.4, 68.5, 49.8, 45.9, 43.5, 42.8, 36.8, 29.6, 29.4,
29.3, 29.0, 28.8, 26.1, 26.0, 19.6; MS (ESI): m/z: calcd for: 555.4; found:
4-Benzyloxy-pyridine-2,6-diethylcarboxylate: 4-Oxo-1,4-dihydropyridine-
2,6-diethylcarboxylate 9 (3.67 g, 0.0153 mol), potassium carbonate (2.3 g,
0.017 mol), and benzyl bromide (1.9 mL, 0.016 mol) were stirred at 858C in
dry DMF (30 mL) for 4 h. Water (200 mL) was added and the mixture
extracted with dichloromethane (2 Â 150 mL). The extracts were washed
with brine, dried, the solvents removed in vacuo, and the residue
recrystallized from ethanol (4.56 g, 77%). 1H NMR (CDCl3): d ˆ 7.84 (s,
2H), 7.45 7.30 (m, 5H), 5.20 (s, 2H), 4.44 (q, J ˆ 7.1 Hz, 4H), 1.42 (t, 6H);
13C NMR (CDCl3): d ˆ 166.7, 164.7, 150.3, 134.9, 129.0, 128.8, 127.9, 114.8,
‡
70.9, 62.5, 14.3; MS (ESI): m/z: calcd for: 329.1; found: 329.9 [M ];
elemental analysis calcd (%) for C18H19NO5: C 65.64, H 5.81, N 4.25; found:
C 65.55, H 5.83, N 4.24.
4-Benzyloxy-pyridine-2,6-dicarboxylic dihydrazide (10): 4-Benzyloxy-pyr-
idine-2,6-diethylcarboxylate (4.50 g, 0.0136 mol) was heated under reflux
with hydrazine hydrate (5 mL) in ethanol (50 mL) for 12 h. The crystalline
precipitate was filtered, washed with diethyl ether and dried to yield white
needles (3.70 g, 92%). 1H NMR (CDCl3): d ˆ 10.64 (s, 2H, NH), 7.66 (s,
2H), 7.50 7.30 (m, 5H), 5.32 (s, 2H), 4.50 (s, 6H, NH); 13C NMR (CDCl3):
d ˆ 167.4, 162.4, 151.2, 136.4, 129.2, 128.9, 128.5, 110.7, 70.6; MS (FAB): m/z:
‡
556.4 [M ].
Self-assembly experiments: Dimerization constants of the monomers and
1
polymers were determined from H NMR experiments by monitoring the
chemical shift of the amide protons at various concentrations (0.0020
0.1000m) in deuterated chloroform. Association constants were measured
by titration of a 0.005m solution of N-butylthymine with 0.010m solutions
of the monomer or polymer, and monitoring the chemical shift of the
butylthymine imide proton. The molarity of the polymer solution is based
on the number of recognition units. The computer program ChemEquili
was used for evaluation of the data.[16]
‡
calcd for: 302.1; found: 302.1 [M H]; elemental analysis calcd (%) for
C14H15N5O3: C 55.81, H 5.02, N 23.24; found: C 54.65, H 5.04, N 23.75.
4-Benzyloxypyridine-2,6-diamine (11): Hydrazide 10 (2.66 g, 0.083 mol)
was suspended in 10% hydrochloric acid (150 mL) at 08C and treated
dropwise with a saturated solution of sodium nitrite until the azide floated
on top as a sticky solid. The azide was isolated by filtration, washed with
water and air-dried. The solid was dissolved in ethanol (100 mL), and
heated under reflux for 12 h to generate the carbamate. The solution was
then reduced to 50 mL, 10% aqueous potassium hydroxide (1:1, 50 mL)
were added, and the mixture heated under reflux for 8 h. The ethanol was
distilled off and the residue extracted with chloroform (3 Â 100 mL). The
extracts were washed with brine, dried, and evaporated to yield the amine
Polymerizations: A typical polymerization experiment was conducted as
following: To a stirred solution of the monomer (0.3 mmol in 1.0 mL
CDCl3), a solution of the ruthenium initiator (0.006 mmol in 0.5 mL
CDCl3) was added. For diaminotriazine monomers, N-butylthymine (0.3
0.9 mmol) was added before addition of the initiator. The mixture was
stirred at ambient temperatures and the reaction progress was monitored
by 1H NMR. After complete conversion, ethyl vinyl ether (0.1 mL) was
added to terminate the reaction. The polymers were precipitated in
hexanes and dried in high vacuum for 24 h.
1
11 as a fluffy white solid (0.87 g, 49%). H NMR ([D6]DMSO): d ˆ 7.40
7.30 (m, 5H), 5.30 (s, 2H), 5.28 (s, 4H, NH), 4.94 (s, 2H); 13C NMR,
([D6]DMSO): d ˆ 167.6, 160.7, 137.8, 129.1, 128.4, 128.1, 82.9, 68.8; MS
‡
(ESI): m/z: calcd for: 215.1; found: 215.8 [M ].
Acknowledgements
4-Benzyloxy-2,6-bis(isobutyrylamino)pyridine: Isobutyryl chloride (1.50 g
14.1 mmol) was slowly added at 08C to a suspension of 11 (1.468 g,
6.82 mmol) and triethylamine (3 mL) in dichloromethane (40 mL). The
reaction mixture was allowed to warm to ambient temperatures and
purified by column chromatography (hexanes/ethyl acetate 1:1) to yield the
The authors would like to thank Eric A. Archer and Prof. Michael J.
Krische (University of Texas, Austin) for kindly providing the ChemEquili
program, and Jacob R. Adams for synthetic work. Acknowledgement is
made to the donors of The Petroleum Research Fund, administered by the
998
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0998 $ 20.00+.50/0
Chem. Eur. J. 2003, 9, No. 4

Universal Polymer Backbone
992 999
ACS, for partial support of this research. A 3M Non-Tenured Faculty
Award is also gratefully acknowledged.
[9] C. G. Overberger, F. W. Michelotti, P. M. Carabateas, J. Am. Chem.
Soc. 1957, 79, 941 944.
[10] a) C. W. Whitehead, J. T. Traverso, H. R. Sullivan, F. J. Marshall, J.
Org. Chem. 1961, 26, 2814 2820; b) H. Hall, A. Padias, A. Buyle, Y.
Li, H. Clever, A. Hester, G. Wang, J. Chem. Soc. Chem. Commun.
1991, 1279 1281.
[11] F. H. Beijer, R. P. Sijbesma, J. A. J. M. Vekemans, E. W. Meijer, H.
Koojman, A. Spek, J. Org. Chem. 1996, 61, 6371 6380.
[12] a) M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1,
953 956; b) C. W. Bielawski, R. H. Grubbs, Angew. Chem. 2000, 112,
3025 3028; Angew. Chem. Int. Ed. 2000, 39, 2903 2906.
[13] R. Deans, F. Ilhan, V. M. Rotello, Macromolecules 1999, 32, 4956
4960.
[14] R. Deans, G. Cooke, V. M. Rotello, J. Org. Chem. 1997, 62, 836 839.
[15] K. A. Connors, BindingConstants , Wiley, New York, 1987.
[16] ChemEquili 6.1, V. Solov×ev, 1996 1998.
[17] D. Breslow, C. Hauser, J. Am. Chem. Soc. 1945, 67, 687 688.
[18] F. Neve, A. Crispini, F. Loiseau, S. Campagna, J. Chem. Soc. Dalton
Trans. 2000, 9, 1399 1402.
[1] For reviews, see: a) J. M. Lehn, Supramolecular Chemistry, Wiley-
VCH, 1995; b) L. J. Prins, D. N. Reinhoudt, P. Timmermann, Angew.
Chem. 2001, 113, 2446 2492; Angew. Chem. Int. Ed. 2001, 40, 2382
2426; c) M. C. T. Fyfe, J. F. Stoddart, Acc. Chem. Res. 1997, 30, 393
401; d) G. Cooke, V. Rotello, Chem. Soc. Rev. 2002, 31, 275 286; e) E.
Archer, A. E. Sochia, M. J. Krische, Chem. Eur. J. 2001, 7, 2059 2065;
f) D. C. Sherrington, K. A. Taskinen, Chem. Soc. Rev. 2001, 30, 83 93.
¬
[2] For selected examples and reviews, see: a) T. Kato, J. M. J. Frechet,
Macromolecules 1989, 22, 3818 3819; b) U. Kumar, T. Kato, J. M. J.
¬
Frechet, J. Am. Chem. Soc. 1992, 114, 6630 6639; c) T. Kato, J. M. J.
¬
Frechet, Macromol. Symp. 1995, 98, 311 326; d) T. Kato, N.
Mizoshita, K. Kanie, Macromol. Rapid Commun. 2001, 22, 797 814.
[3] a) J. Ruokolainen, R. M‰kinen, M. Torkkeli, T. M‰kel‰, R. Serimaa,
G. ten Brinke, O. Ikkala, Science 1998, 280, 557 560; b) O. Ikkala, G.
ten Brinke, Science 2002, 295, 2407 2409.
[4] T. H. Galow, F. Ilhan, G. Cooke, V. M. Rotello, J. Am. Chem. Soc.
2000, 122, 3595 3598.
[5] H. Asamuna, T. Hishya, T. Ban, S. Gotoh, M. Komiyama, J. Chem.
Soc. Perkin Trans. 2 1998, 1915 1917.
[6] F. Ilhan, M. Gray, V. M. Rotello, Macromolecules 2001, 34, 2597
2601.
[19] K. Naemura, M. Nakazaki, Bull. Chem. Soc. Jpn. 1973, 46, 888 892.
[20] J. M. Pollino, M. Weck, Synthesis 2002, 1277 1285.
[21] G. Chessa, A. Scrivanti, J. Chem. Soc. Perkin Trans. 1 1996, 307 312.
[22] a) E. R. Riegel, F. Zwilgmeyer, Org. Synth. Coll. Vol. 2, Wiley, New
York, 1968, p. 126–128; b) A. O. Fitton, Practical Heterocyclic
Chemistry, Academic Press, New York, 1968, p. 74.
[7] T. M. Trnka, R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18 29.
[8] E. Smolin, L. Rapoport, The Chemistry of Heterocyclic Compounds,
Vol. 13: s-Triazines, Interscience, New York, 1959.
Received: September 9, 2002 [F4405]
Chem. Eur. J. 2003, 9, No. 4
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0904-0999 $ 20.00+.50/0
999