Determining the regioregularity in alkyne polycarbodiimides and their orthogonal modification of side chains to yield perfectly alternating functional polymers

Article abstract of DOI:10.1021/ma301639m

To understand the structure-property relationship in functional macromolecules through side chain modulation, both the accurate determination of the position of modifiable groups along the polymer chain and their subsequent modifications using high fideli

Full text of DOI:10.1021/ma301639m

Article
pubs.acs.org/Macromolecules
Determining the Regioregularity in Alkyne Polycarbodiimides and
Their Orthogonal Modification of Side Chains To Yield Perfectly
Alternating Functional Polymers
Januka Budhathoki-Uprety,† James F. Reuther,† and Bruce M. Novak*,‡
†Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States
‡Department of Chemistry and the Alan G MacDiarmid NanoTech Institute, University of Texas at Dallas, Richardson, Texas
75080-3021, United States
S
* Supporting Information
ABSTRACT: To understand the structure−property relation-
ship in functional macromolecules through side chain
modulation, both the accurate determination of the position
of modifiable groups along the polymer chain and their
subsequent modifications using high fidelity methods are
crucial. In this report, the polymer microstructure of a helical
alkyne polycarbodiimide has directly been probed through 15
N
NMR spectroscopy on isotopic labeled poly(N-(3-ethynylphe-
nyl)-15N′-hexyl)carbodiimide and found to be a highly
regioregular polymer structure. This polymer undergoes facile
and quantitative CuAAC “click” chemistry, yielding perfectly
alternating functional polymers. Advances have been made through the synthesis of new optically active alkyne
polycarbodiimides with two independently modifiable pendant groups per repeat unit of polymers. Orthogonal postmodifications
of the pendant groups were then performed to incorporate two different sets of small molecules in the repeat unit of polymers in
a controlled manner and under mild reaction conditions using either sequential CuAAC “click” reactions when two dissimilar
alkyne groups are present or a combination of CuAAC and thiol−ene click chemistries when pendant groups bear alkyne and
vinyl moieties.
understanding of the structure−property relationship, it is
important to ascertain the position of modiafiable alkyne
groups along the polymer chain prior to their further
modification. As such, for designing new functional polymer
derivatives, both the highly efficient functional group
modulation and ascertaining the positions of modifiable groups
along polymer chains are crucial. Here, we chose poly(N-(3-
ethynylphenyl)-N′-hexyl)carbodiimide, an example of alkyne
polycarbodiimide derived from a nonsymmetric monomer, to
unravel whether the mode of distribution of alkyne pendant
groups along the polymer chain is regioregular or regiorandom.
The coordination−insertion polymerization of carbodiimide
monomers using titanium(IV) alkoxide catalysts to obtain
polycarbodiimides (including the one mentioned earlier) may
yield a multitude of polymer regiostructures.4 For instance, the
use of symmetric carbodiimide monomers in polymerization
results in polycarbodiimides with uniform repeat units. On the
other hand, polycarbodiimides derived from asymmetric
monomers, in principle, can result in a regic (regioregular
distribution of pendant groups), syndioregic (alternate
INTRODUCTION
■
The synthesis of functional helical polymers has been an active
area of research interest due to their wide range of potential
applications such as chiral recognition and separation media,
asymmetric catalysis, chiral template, chiral amplification,
optical displays, and biomimetic materials.1−8 Polymer proper-
ties vastly rely on their microstructures, and in many of those
synthetic helical polymers, specific properties have been
achieved through versatile side chains. As an example, helical
polycarbodiimides have shown many remarkable properties
such as thermo- and solvo-controllable chiroptical switching,
liquid crystalline structure, and chiral orienting media through
modulations of their side chains.6,9−12 To further expand the
properties of these polycarbodiimides with functional side
chains, postmodification of a polymer sample is a versatile
method. In a previous publication, we demonstrated that a
family of alkyne functionalized polycarbodiimides undergo
facile and quantitative postmodifications in the copper-
catalyzed azide−alkyne cycloaddition (CuAAC) “click” and
Sonogashira coupling reactions involving a variety of functional
groups along the side chains of polymers.13 These unprece-
dented functionalizations of side chains in polycarbodiimides
help extend the useful properties of this polymer system, of
which antibacterial activity is an example.14 For fundamental
Received: August 3, 2012
Revised: September 25, 2012
Published: October 2, 2012
© 2012 American Chemical Society
8155
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
Figure 1. Some of the possible microstructures in polycarbodiimides represented by pentamer structures: A and B (regic), C (syndioregic), and D
(aregic).
distribution of pendant groups), or aregic (regiorandom
distribution of pendant groups) microstructure (Figure 1)
due to configurational choices for a side group to bond to either
imine nitrogen or amine nitrogen in the repeat unit of the
polymer.
EXPERIMENTAL SECTION
■
General. Chemicals were purchased from commercial venders
Sigma-Aldrich, Milwaukee, WI; Fisher Scientific, Fair Lawn, NJ; Acros
Organics; and Strem Chemicals, Newburyport, MAand were used as
received unless stated otherwise. The certified ACS grade solvents
were purchased from Fisher Scientific and used as received except
tetrahydrofuran (THF), which was distilled prior to use. Column
chromatography on monomers was performed using high purity silica
To study the regioregularity in polycarbodiimides, 13C NMR
signals in polymers can be obtained without isotope enrichment
of a polymer sample but are often poorly resolved. IR spectra of
polycarbodiimides show strong signals at ca. 1620−1650 cm−1
corresponding to imine group in the polymer backbone, but
this window of IR absorption (1620−1640 cm−1) has recently
been discovered to include a number of stretch and/or bending
modes that are associated with conformational changes in some
polycarbodiimides.15 Those limitations stymied the accurate
determination of regio(ir)regularity in polycarbodiimides using
the aforementioned methods and demand an additional
characterization tool. Recently, our group reported 15N NMR
spectroscopy as a new characterization method to precisely
determine regioiregularity in poly(N-n-hexyl-N′-phenylcarbo-
diimide), Poly-2 (Figure 2), a polycarbodiimide sample derived
from a nonsymmetric carbodiimide monomer.16 Although the
spectroscopy requires isotopic enrichment of a polymer sample
with 15N isotope, the high resolution of the spectral signals and
distinct chemical shifts observed for amine nitrogen compared
with that of imine nitrogen (separated by ∼100 ppm) in repeat
unit of polymers make 15N NMR spectroscopy the most
reliable method to date for directly probing regio(ir)regularity
in polycarbodiimides involving a wide range of pendant groups.
Here, we use 15N NMR spectroscopy to unravel the
regioregularity in an alkyne polycarbodiimide derived from a
nonsymmetric carbodiimide monomer. Upon confirmation of
regioregularity in polycarbodiimides with aliphatic and directly
attached aromatic side chains, of special note is Poly-1, we
extended our study on functional polycarbodiimides through
the synthesis of new alkyne polycarbodiimides with two
independently modifiable alkyne functionalities: 1-hexyne and
protected phenylacetylene groups in repeat units. The
orthogonal postmodification of these alkyne moieties were
performed in consecutive “click” reactions in a controlled
fashion under mild reaction conditions. In addition, this report
also includes the synthesis of an optically active polycarbodii-
mide with two orthogonal clickable groups, an alkyne and a
styrene side chains for the first time, followed by orthogonal
side chain modulation in two consecutive click chemistries:
azide−alkyne and thiol−ene.
1
gel, either neutral (purchased) or neutralized with triethylamine. H,
13C, and 15N NMR data were recorded on Mercury spectrometers
1
(300 or 400 MHz for H NMR, 75 or 100 MHz for 13C NMR, and
40.5 MHz for 15N NMR) at room temperature. The chemical shift
values were reported relative to TMS (δ = 0.00 ppm) or
corresponding solvents as an internal standard for H and 13C NMR
1
and 15N-benzamide (δ = 0.00 ppm) as an external standard for 15N
NMR. A small amount (ca. 5 mg) of gadolinium(III) acetylacetate,
Gd(acac)3, was added in an ∼35 mg polymer sample in CDCl3 prior to
15N NMR data collection over the period of 8 h. IR spectra were
obtained from a JASCO FT/IR-410. Wavenumbers in cm−1 are
reported for characteristic peaks. Mass spectra (HRMS) were obtained
at the NCSU Department of Chemistry Mass Spectrometry Facility
using electrospray ionization (ESI) on an Agilent Technologies 6210
LC-TOF mass spectrometer. Specific optical rotation was recorded on
a JASCO P-1010 polarimeter. All the manipulations for polymer-
izations were performed at room temperature inside an MBraun
UNIlab drybox under a nitrogen atmosphere. Size exclusion
chromatography (SEC) was performed on a Viscotek VE 3580 system
equipped with ViscoGEL columns (GMHHR-M) connected to a
refractive index (RI) detector at 30 °C using 0.12 M diethanolamine in
THF as an eluent to determine relative molecular weights of the
polymers. Polystyrene standards were used for the calibration of the
instrument. Polymer samples were dissolved in the solvent system
containing 0.12 M diethanolamine in THF, and the solutions were
filtered through 0.45 μm PTFE filters prior to injection. The flow rate
was 1.0 mL/min, and injector volume was 100 μL.
Chemistry. Synthesis of Isothiocyanate Derivatives from
Corresponding Amines. Isothiocyanate derivatives were prepared
with a slight modification in the literature procedure from ref 20.
Thiophosgene (1.2 equiv) was added dropwise to a stirred mixture of
desired amine (1.0 equiv) and triethylamine (4.0 equiv) in
dichloromethane (∼20 mL for the reaction scale mentioned below)
at 0 °C under a nitrogen atmosphere. Thiophosgene is toxic and
should be handled with care. The reaction mixture was stirred at room
temperature overnight, after which the organic layer was washed with
DI water (10 mL × 4) and brine (10 mL × 2), separated, dried over
anhydrous Na2SO4, filtered, and concentrated on a rotary evaporator.
A viscous, dark brown liquid thus obtained was purified by column
chromatography in silica gel using a mixture of ethyl acetate and
hexane (1:1 by volume) to afford desired compound as colorless to
light yellow oil.
1-Ethynyl-3-isothiocyanatobenzene, Compound 6. Light yellow
oil, 80% yield. 1H NMR (400 MHz, CDCl3, δ ppm); reference: CDCl3
8156
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
volume) as mobile phase to afford desired thiourea derivative as off-
white solid or thick viscous liquid.
1-(Hex-5-ynyl)-3-(3-(2-(trimethylsilyl)ethynyl)phenyl)thiourea,
Compound 13a. Thick viscous liquid, 0.50 g, 71% yield (yield varied
= 7.24 ppm, δ = 7.39−7.21 (m, 4H), 3.13(s, 1H). 13C NMR (100
MHz, CDCl3, δ ppm): reference CDCl3 = 77.23 ppm, δ = 136.6,
131.6, 130.8, 129.6, 129.0, 126.0, 123.7, 81.8, 78.8. FTIR (KBr thin
film, neat, cm−1): 3294, 3064, 2958 (w), 2142 and 2102 (vs, NC
S), 1591, 1573, 790 (s).
(2-(3-Isothiocyanatophenyl)ethynyl)trimethylsilane, Compound
10a. The solvent used in purification by column chromatography
1
71−85% in different runs). H NMR (400 MHz, CDCl3, δ ppm):
reference CDCl3 = 7.24 ppm, δ = 7.87(s, 1H), 7.38−7.13 (m, 4H),
6.03 (br, s, 1H), 3.66−3.65 (m, 2H), 2.21 (td, J = 6.8 Hz, 2.8 Hz, 2H),
1.91 (t, J = 2.8 Hz, 1H), 1.72−1.67 (m, 2H), 1.57−1.52 (m, 2H), 0.24
(s, 9H). 13C NMR (100 MHz, CDCl3, δ ppm): reference CDCl3 =
77.23 ppm, δ = 180.8, 136.2, 131.0, 130.3, 128.6, 125.6, 125.5, 103.4,
96.6, 84.1, 69.0, 45.1, 28.1, 25.7, 18.2, 0.1. HRMS (ESI) m/z: [M +
H]+: calcd for C18H24N2SSi, 329.1502; found, 329.1493. FTIR (KBr
thin film, neat, cm−1): 3289 (vs, CC−H), 3062, 2956 (s, alkyl C−
H), 2863 (w), 2057 (s, CC−TMS), 2115 (w, CC−H), 1598,
1579, 1538 (s), 1484, 1249 (s), 844 (vs).
was a mixture of petroleum ether and dichloromethane (3:1
respectively) to afford compound 10a as light yellow oil (0.41 g,
68% yield). 1H NMR (400 MHz, CDCl3, δ ppm); reference: CDCl3 =
7.24 ppm, δ = 7.35−7.25 (m, 3H), 7.16−7.13 (m, 1H), 0.24 (s, 9H);
13C NMR (100 MHz, CDCl3, δ ppm): reference CDCl3 = 77.23 ppm,
1-(Hex-5-ynyl)-3-(3-(2-(triisopropylsilyl)ethynyl)phenyl)thiourea,
Compound 13b. Off-white solid, 0.99 g, 76% yield (yield varied 76−
δ = 136.6, 131.6, 130.8, 129.6, 129.2, 125.8, 125.0, 103.2, 96.4, 0.03.
FTIR (KBr thin film, neat, cm−1): 3066, 2958 (s, alkyl C−H), 2898
(w), 2051 (vs, NCS), 1594, 1573, 1249 (s), 860 (vs), 842 (vs).
Triisopropyl(2-(3-isothiocyanatophenyl)ethynyl)silane, Com-
pound 10b. 1.01 g, 88% yield. 1H NMR (400 MHz, CDCl3, δ
97% in different runs) 1H NMR (400 MHz, CDCl3, δ ppm): reference
TMS = 0.00 ppm, δ = 7.77 (s, br 1H), 7.41−7.31 (m, 3H), 7.15 (d, J =
7.6 Hz, 1H), 6.03 (br, s, 1H), 3.67 (q, J = 6.4 Hz, 2H), 2.22 (td, J = 6.4
Hz, 2.4 Hz, 2H), 1.91 (t, J = 2.4 Hz 1H), 1.75−1.68 (m, 2H), 1.59−
1.51 (m, 2H), 1.12 (s, 21H). 13C NMR (100 MHz, CDCl3, δ ppm):
reference CDCl3 = 77.23 ppm, δ = 180.9, 136.2, 131.0, 130.4, 128.8,
125.9, 125.5, 105.5, 93.2, 84.0, 69.0, 45.1, 28.1, 25.7, 18.8, 18.2, 11.4.
HRMS (ESI) m/z: [M + H]+ calcd for C24H36N2SSi, 413.2441; found,
413.2443. FTIR (KBr thin film, neat, cm−1): 3293 (vs, CC−H and
N−H), 3056 (w), 2942 (s, alkyl C−H), 2863 (s), 2054 (s, CC−
TMS), 2117 (w, CC−H), 1538 (s), 1484, 1292.
ppm); reference TMS = 0.00 ppm, δ = 7.36 (dt, J = 7.6 Hz, 1.2 Hz,
1H), 7.32 (t, J = 1.2 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 7.15 (dq, J = 7.6
Hz, 1.2 Hz, 1H), 1.12 (s, br, 21H); 13C NMR (100 MHz, CDCl3, δ
ppm): reference CDCl3 = 77.23 ppm, δ = 131.0, 129.6, 129.2, 125.6,
125.3, 105.2, 93.0, 18.8, 11.4. FTIR (KBr thin film, neat, cm−1): 3066,
2942 (s, alkyl C−H), 2890 (w), 2863, 2051 (vs, NCS), 1592,
1573, 1469, 881 (m), 833 (m), 678.
1-Isothiocyanato-4-vinylbenzene, Compound 15. 0.982 g, 82%
1-(3-Ethynylphenyl)-3-hexylthiourea, Compound 7. Sticky viscous
mass, 0.65 g, 91% yield. 1H NMR (300 MHz, CDCl3, δ ppm):
yield (orange oil). 1H NMR (400 MHz, CDCl3, δ (ppm): 7.37 (td, J =
reference CDCl3 = 7.24 ppm, δ = 7.86 (s, 1H), 7.41−7.20 (m, 4H),
6.03 (dt, J = 6.0 Hz, 87.0 Hz, 1H), 3.65−3.58 (m, 2H), 3.15 (s, 1H),
1.62−1.55 (m, 2H), 1.32−1.28 (m, 6H), 0.87 (t, J = 6.6 Hz, 3H). 13C
NMR (100 MHz, CDCl3, δ ppm): reference CDCl3 = 77.23 ppm, δ =
180.4 (d), 180.3, 130.7, 130.2, 128.4, 125.5, 108.5, 82.1, 78.8, 45.6,
31.3, 28.8, 26.5, 22.5, 13.9. FTIR (KBr thin film, neat, cm−1): 3290
(vs), 3062, 2954 (s, alkyl C−H), 2929, 2856 (w), 2107 (w, CC−H),
1598, 1579, 1523 (s), 1336, 1288 (s), 1249 (s), 1249, 647. 15N NMR
(40.5 MHz, CDCl3, δ ppm): reference (external standard) 15N-
benzamide = 0.00 ppm, δ = 18.93 ppm.
8.0 Hz, J = 1.4 Hz, Ar−H, 2H), 7.19 (td, J = 8.8 Hz, J = 4.0 Hz, Ar−H,
2H), 6.67 (dd, J = 17.6 Hz, J = 11.2 Hz, vinyl−H, 1H), 5.74 (d, J =
18.8 Hz, vinyl−H, 1H), 5.31 (d, J = 11.6 Hz, vinyl−H, 1H). 13C NMR
(100 MHz, CDCl3, δ ppm): 136.9, 135.8, 127.5, 126.1, 115.5, 94.5.
FTIR (KBr salt plate, cm−1): 3087 (w, Ar−H), 3037 (w, Ar−H), 3008
(w, vinyl−H), 2100 (s, SCN−), 1598 (CC aryl, m).
Synthesis of Thiourea Derivatives. Isothiocyanate (1.0 equiv)
diluted in dichloromethane (10 mL for 1.0 g isothiocyanate) was
added to a stirred solution of desired amine (1.04 equiv) in
dichloromethane (20 mL) at 0 °C. The reaction mixture was stirred
at room temperature until completion (ca. 1 h for 13a and 13b) as
observed under FTIR analysis. The solvent was removed in a rotary
evaporator, and sticky viscous residue was purified through column
chromatography in silica gel using a mixture of hexane and ethyl
acetate (2:1 by volume respectively) or CH2Cl2: ethyl acetate (6:1 by
1-(Hex-5-ynyl)-3-(4-vinylphenyl)thiourea, Compound 16. Off-
white powder, 0.860 g, 61% yield. FTIR (KBr salt plate, cm−1):
3295 (s, N−H and CC−H, overlapped), 3086 (w, Ar−H), 3043 (w,
Ar−H), 2979 (s, vinyl−H), 2938 (s, alkyl−H), 2864 (m, alkyl−H),
1
2115 (m, CC), 1538 (s, SC). H NMR (400 MHz, CDCl3, δ
ppm): 8.11 (N−H, s, 1H), 7.45 (td, J = 8.8 Hz, J = 2.4 Hz, Ar−H,
2H), 7.16 (d, J = 8.4 Hz, Ar−H, 2H), 6.69 (dd, J = 17.6 Hz, J = 11.2
8157
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
carbodiimide), 1670, 1596, 1573, 1249 (s), 844 (vs). HRMS (ESI)
m/z: [M + H]+ calcd for C18H22N2Si, 295.1625; found, 295.1631.
N-((Hex-5-ynylimino)methylene)-3-(2-(triisopropylsilyl)ethynyl)-
benzenamine, Compound 14b. Clear oil, 0.63 g, 90% yield. 1H NMR
Hz, vinyl−H, 1H), 6.07 (N−H, s, 1H), 5.74 (d, J = 17.6 Hz, vinyl−H,
1H), 5.30 (d, J = 10.4 Hz, vinyl−H, 1H), 3.65 (q, J = 7.2 Hz, N−
CH2−, 2H), 2.21 (m, −CH2CH2CH2CH2CCH, 2H), 1.89 (t, J =
2.4 Hz, −CH2CCH, 1H), 1.71 (m, −CH2CH2CH2CH2CCH,
2H), 1.53 (m, −CH2CH2CH2CH2CCH, 2H). 13C NMR (100
MHz, CDCl3, δ ppm): 180.8, 136.8, 135.8, 128.1, 125.5, 115.3, 84.1,
69.1, 45.2, 28.3, 25.8, 18.3.
(400 MHz, CDCl3, δ ppm): reference TMS = 0.00 ppm, δ = 7.22−
7.17 (m, 3H), 7.03−7.00 (m, 1H), 3.47 (t, J = 6.8 Hz, 2H), 2.25 (td, J
= 6.8 Hz, 2.4 Hz, 2H), 1.96 (t, J = 2.4 Hz 1H), 1.85−1.78 (m, 2H),
1.70−1.63 (m, 2H), 1.12 (s, 21H). 13C NMR (100 MHz, CDCl3, δ
ppm): reference CDCl3 = 77.23 ppm, δ = 140.8, 135.4, 129.4, 128.5,
127.0, 124.8, 123.8, 106.5, 91.3, 83.8, 69.1, 46.4, 30.3, 25.7, 18.8, 18.1,
11.4. FTIR (KBr thin film, casted from CHCl3, cm−1): 3309 (s), 3064
(w), 2942 (s, alkyl C−H), 2890, 2863 (s), 2140 (vs, NCN),
1594, 1575, 1463. HRMS (ESI) m/z: [M + H]+ calcd for C24H34N2Si,
379.2564; found, 379.2559.
Synthesis of Urea Derivative: 1-(Hex-5-ynyl)-3-phenylurea.
Phenyl isocyanate (0.32 g, 2.67 mmol) was added dropwise to a
N-(3-Ethynylphenyl)-15N′-hexylcarbodiimide, Compound 8. Col-
1
orless oil, 0.39 g, 83% yield. H NMR (400 MHz, CDCl3, δ ppm,
stirred solution of amine 12 (0.26 g, 2.67 mmol) in dichloromethane
(5 mL) at 0 °C. After complete addition, the ice bath was removed,
and the reaction mixture in a closed cap vial was stirred at room
temperature until completion (ca. 1 h). The reaction mixture was
concentrated in a rotary evaporator to remove all the solvent.
Recrystallization of the yellow sticky mass at low temperature (−78
°C) afforded 1-(hex-5-ynyl)-3-phenylurea as white solid (0.5 g, 87%
reference TMS = 0 ppm): 7.23−7.20 (m, 3H, Ar−H), 7.07−7.05
(m,1H, Ar−H), 3.41 (t, J = 7.2, 2H), 3.07 (s,1H, sp C−H), 1.70−1.65
(m, 2H), 1.43−1.29 (m, 6H), 0.88 (t, J = 7.2, 3H, −CH3). 13C NMR
(100 MHz, CDCl3, δ ppm, reference CDCl3 = 77.23 ppm): δ = 141.3,
135.2 (d), 129.5, 128.3, 127.1, 124.2, 123.3, 83.2, 77.7, 46.9 (d), 31.4,
26.6, 22.7, 14.1. FTIR (cm−1): 3294 (terminal alkyne C−H), 3066,
2929, 2858, 2121 (vs, NCN), 1594, 1575, 1481, 617; HRMS
(ESI) m/z: [M + H]+ calcd for C15H18[15N], 228.1513; found,
228.1518.
1
yield). H NMR (400 MHz, CDCl3, δ ppm): reference TMS = 0.00
ppm, δ = 7.70 (br, 1H), 7.30−7.20 (m, 4H), 7.00−7.07 (t, 1H), 5.59
(br, 1H), 3.15 (t, J = 6.4 Hz, 2H), 2.13 (td, J = 6.4 Hz, J = 2.8 Hz, 2H),
1.92 (t, J = 2.8 Hz, 1H), 1.52−1.47 (m, 4H). 13C NMR (100 MHz,
CDCl3, δ ppm): reference CDCl3 = 77.23 ppm, δ = 157.0, 138.8,
129.2, 129.1, 123.5, 120.8, 84.2, 68.8, 39.9, 29.3, 25.8, 18.2. FTIR (KBr
thin film, casted from CHCl3, cm−1): 3299 (vs, CC−H and N−H),
3056, 2938 (s, alkyl C−H), 2863 (m), 2115 (w, CC−H), 1644 (vs),
1596, 1523, 1500, 1440, 1313, 1236.
N-Hex-5-yn-1-yl-N′-phenylcarbodiimide. Colorless oil, 0.35 g, 76%
1
yield. H NMR (400 MHz, CDCl3, δ ppm): reference CDCl3 = 7.24
Synthesis of Monomers. Triethylamine (2.5 equiv) was added
dropwise to a stirred suspension of PPh3Br2 (1.2 equiv) in
dichloromethane (10 mL for 1.0 g scale of the reagent) at 0 °C
under a nitrogen atmosphere. After 5 min, urea or thiourea derivative
(1.0 equiv) was added slowly to the reaction mixture. The reaction was
stirred at low temperature for 1 h and then at room temperature until
completion. Once the reaction was complete as monitored by FTIR
spectroscopy, solvent was removed in a rotary evaporator and the
crude monomer product was extracted with pentane from solid
residue. The process was repeated to extract all of the crude monomer,
and the solution was concentrated in a rotary evaporator. The crude
oily product thus received was purified by column chromatography in
silica gel using a mixture of ethyl acetate:hexane (1:4 by volume) along
with 2% triethylamine to afford desired carbodiimide monomer as oily
liquid in all cases.
ppm, δ = 7.30−7.25 (m, 2H), 7.10−7.07 (m, 3H), 3.45 (t, J = 6.8 Hz,
2H), 2.25 (td, J = 6.8 Hz, J = 2.8 Hz, 2H), 1.96 (t, J = 2.8 Hz, 1H),
1.84−1.77 (m, 2H), 1.70−1.63 (m, 2H). 13C NMR (100 MHz, CDCl3,
δ ppm): reference CDCl3 = 77.23 ppm, δ = 140.6, 129.8, 129.5, 124.8,
123.7, 83.9, 69.0, 46.5, 30.4, 25.7, 18.1. FTIR (KBr thin film, casted
from CHCl3, cm−1): 3295 (s), 3062 (w), 2944 (m, alkyl C−H), 2865
(w), 2140 (vs, NCN), 1698 (w), 1594, 1500.
N-(4-Ethenylphenyl)-N′-hex-5-yn-1-ylcarbodiimide, Compound
17. Pale yellow oil, 0.418 g, 58% yield. FTIR (KBr salt plate, cm−1):
N-((Hex-5-ynylimino)methylene)-3-(2-(trimethylsilyl)ethynyl)-
benzenamine, Compound 14a. Pale yellow oil, 0.236 g, 88% yield.
3293 (s, CC−H), 3060 (w, Ar−H), 2954 (m, alkyl−H), 2929 (s,
alkyl−H), 2857 (s, alkyl−H), 2140 (s, NCN), 1597 (s, CCaryl).
1H NMR (400 MHz, CDCl3, δ ppm): 7.33 (td, J = 11.6 Hz, J = 2.8 Hz,
Ar−H, 2H), 7.03 (td, J = 11.6 Hz, J = 2.8 Hz, Ar−H, 2H), 6.67 (dd, J
= 23.6 Hz, J = 14.8 Hz, vinyl−H, 1H), 5.67 (d, J = 23.2 Hz, vinyl−H,
1H), 5.20 (d, vinyl−H, J = 14.8 Hz, 1H), 3.47 (t, J = 8.4 Hz, N−
CH2−, 2H), 2.25 (td, J = 9.2 Hz, J = 3.2 Hz, −CH2CH2CH2CH2C
CH, 2H), 1.96 (t, J = 3.6 Hz, −CH2CCH, 1H), 1.80 (m,
−CH2CH2CH2CCH, 2H), 1.67 (m, −CH2CH2CH2CCH, 2H).
1H NMR (400 MHz, CDCl3, δ ppm): reference CDCl3 = 7.24 ppm, δ
= 7.18−7.15 (m, 3H), 7.0−6.98 (m, 1H), 3.45 (t, J = 6.8 Hz, 2H), 2.23
(td, J = 6.8 Hz, 2.8 Hz, 2H), 1.95 (t, J = 2.8 Hz 1H), 1.82−1.75 (m,
2H), 1.67−1.60 (m, 2H), 0.22 (s, 9H). 13C NMR (100 MHz, CDCl3,
δ ppm): reference CDCl3 = 77.23 ppm, δ = 140.8, 129.7, 129.4, 128.4,
126.9, 124.3, 124.0, 104.5, 94.8, 83.9, 69.1, 46.4, 30.3, 25.7, 18.1, 0.1.
FTIR (KBr thin film, neat, cm−1): 3301 (s, terminal alkyne C−H),
3062, 2956 (s, alkyl C−H), 2865 (w), 2140 (vs, NCN,
8158
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
13C NMR (100 MHz, CDCl3, δ ppm): 140.2, 136.3, 132.6, 128.8,
127.4, 123.8, 113.4, 69.1, 46.6, 30.5, 25.8, 18.2. HRMS-ESI: Mtheoretical
= 225.1386, Msample = 225.1377, ΔM = 0.92 mass units (4.13 ppm)
C15H16N2.
0.15−0.13 (br). 13C NMR (100 MHz, CDCl3, δ ppm): reference
CDCl3 = 77.23 ppm, δ = 149.2, 147.5, 129.9, 126.9, 125.0, 123.3,
105.1, 94.9, 84.7, 68.5, 48.0, 28.3, 25.7, 18.1, 0.2. FTIR (KBr thin film,
cm−1): 3307 (s, −CC−H), 3052 (Ar−H), 2958 (s, alkyl C−H),
2156 (s, −CC−TMS), 2119 (w, −CC−H), 1625 (imine).
Synthesis of Polymers. All the manipulations for polymerization
were performed inside a glovebox under a nitrogen atmosphere and at
room temperature. Polymerization catalyst, R-BINOL Ti(IV)
diisopropoxide, was added to a stirred solution of carbodiimide
monomer in the desired monomer to catalyst ratio (∼100:1 or 50:1).
The reaction mixture was stirred until stir bar seized from stirring (ca.
1−2 h). The reaction mixture was left inside the glovebox for 24 h
prior to work up for purification. In FTIR, the complete loss of a very
strong band corresponding to carbodiimide functionality (∼2140
cm−1) and emergence of strong band at 1620−1650 cm−1
corresponding to imine functionality indicates that the polymerization
reaction was complete. Resulted pale yellow solid was dissolved in
chloroform and precipitated in methanol (a common antisolvent for
polycarbodiimides), separated by filtration, washed with methanol, and
dried under reduced pressure to afford desired polymer.
21
[α]589 = 367° (c = 0.2 in CHCl3, l = 0.5 dm).
Poly(N-hex-5-yn-1-yl-N′-(3-(2-triisopropysilyl)ethynylphenyl)-
carbodiimide), Poly-6. White fibrous solid (0.469 g, 80% yield,
Poly(N-(3-ethynylphenyl)-15N′-hexylcarbodiimide), Poly-1. Pale
yellow solid (0.28 g, 80% yield), monomer:catalyst (molar ratio)
monomer:catalyst ratio used (100:1)). 1H NMR (400 MHz, CDCl3, δ
ppm): reference TMS = 0.00 ppm, δ = 7.07 (br), 3.70 (br), 2.45 (br),
1.71−1.61 (br), 1.25, 1.06−1.00 (br). 13C NMR (100 MHz, CDCl3, δ
ppm): reference CDCl3 = 77.23 ppm, δ = 148.3, 147.8, 129.4, 127.7,
123.6, 107.1, 91.5, 84.2, 68.3, 48.0, 29.9, 25.7, 18.8, 11.5. FTIR (KBr
thin film, casted from CHCl3, cm−1): 3313 (s, −CC−H), 3060 (w,
Ar−H), 2942 (s, alkyl C−H), 2892, 2865 (s), 2152 (s, −CC−
TMS), 2121 (w, −CC−H), 1631 (vs, imine), 1587, 1571, 1463,
21
100:1. 1H NMR (400 MHz, CDCl3, δ ppm, reference TMS = 0 ppm):
7.60−6.20 (br, Ar−H), 4.0−2.2 (br), 3.0 (br, s, Sp C−H), 1.8−0 (br).
FTIR (cm−1): 3305 (terminal alkyne C−H), 2107 (CC), 1629
(imine). 15N NMR (40.5 MHz, CDCl3, δ ppm): reference (external
standard) 15N-benzamide = 0.00 ppm; δ = 13.91 ppm.
1384, 1243, 1149, 1130, 663. [α]589 = 125° (c = 0.22 in CHCl3, l =
0.5 dm).
Poly(N-(4-ethenylphenyl)-N′-hex-5-yn-1-ylcarbodiimide), Poly-
10. Dilute solution of (S)-BINOL titanium(IV) diisopropoxide in
Poly(N-hex-5-yn-1-yl-N′-phenylcarbodiimide), Poly-3. White fi-
brous solid (0.18 g, 76% yield). 1H NMR (400 MHz, CDCl3, δ ppm):
dry CHCl3 (0.100 mL (14.5 μmol, 1.0 equiv)) was used to polymerize
0.404 g (1.80 mmol, 124 equiv) of N-(4-ethenylphenyl)-N′-hex-5-yn-
1-ylcarbodiimide. Polymer: pale-orange solid (0.319 g, 79% yield). 1H
NMR (400 MHz, CDCl3, δ ppm): 7.25 (Ar−H, br, d, 2H), 7.67 (Ar−
H/vinyl−H, br, d, 3H), 5.59 (vinyl−H, br, s, 1H), 5.12 (vinyl−H, br, s,
1H), 3.54 (N−CH2−, br, s, 1H), 2.56 (N−CH2−, br, s, 1H), 1.90
(CC−H, s, 1H), 1.56−0.58 (alkyl-H, br, 6H). FTIR (KBr salt plate,
cm−1): 3295 (s, −CC−H), 3083 (w, Ar−H), 3008 (w, vinyl−H),
2944 (m, alkyl−H), 2115 (w, −CC−H), 1623 (s, CN), 1595 (s,
reference CDCl3 = 7.24 ppm, δ = 7.09 (br), 6.85−6.76 (br), 3.53 (br),
2.56 (br), 1.90 (br, CC−H), 1.59−1.51 (br), 0.83 (br), 0.56 (br).
13C NMR (100 MHz, CDCl3, δ ppm): reference CDCl3 = 77.23 ppm,
δ = 148.3, 147.6, 128.8, 121.9, 84.5, 68.4, 46.7, 27.5, 25.3, 18.0. FTIR
(KBr thin film, casted from CHCl3, cm−1): 3297 (s, CC−H), 3058
(Ar−H), 3018, 2942 (s, alkyl C−H), 2115 (m, CC−H), 1631 (vs,
imine), 1589, 1484, 1375, 1243, 1145, 1083, 630. [α]58921 = 365° (c =
0.2 in CHCl3, l = 0.5 dm).
25
Poly(N-hex-5-yn-1-yl-N′-(3-(2-trimethylsilyl)ethynylphenyl)-
CCaryl). [α]435 = (−)128° (c = 0.2 in CHCl3, l = 0.5 dm).
1
carbodiimide), Poly-5. White solid (0.436 g, 85% yield). H NMR
The CuAAC “click” chemistry was performed using the procedure
as reported in ref 13. The thiol−ene reaction was performed using the
literature procedure as described in ref 33 (details available in
Supporting Information). The alkyne-protected aniline derivative 9a
was synthesized by Sonogashira coupling reaction of trimethylsilyla-
cetylene, TMSA (0.717 g, 7.3 mmol), and 3-iodoaniline (1.0 g, 4.56
mmol) in the presence of Pd(PPh3)4 (0.26 g, 0.23 mmol), CuI (0.087
g, 0.45 mmol), and PPh3 (0.12 g, 0.45 mmol) in triethylamine (5.0
mL) under a nitrogen atmosphere, with a slight modification of
literature procedure.17 The synthesis of hex-5-yn-1-amine from
commercial 6-chloro-hex-1-yne was performed with a slight
modification of the literature procedure.18 Details on synthesis and
characterization of those compounds are available in the Supporting
Information.
(400 MHz, CDCl3, δ ppm): reference CDCl3 = 7.24 ppm, δ = 7.00
(br), 3.65 (br), 2.40 (br), 1.82 (br, −CC−H), 1.62 (br), 0.85 (br),
8159
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
Scheme 1. Synthesis of 15N Labeled Alkyne Polymer, Poly-1
Figure 2. 15N NMR spectrum of poly(N-(3-ethynylphenyl)-15N′-hexyl)carbodiimide, Poly-1, showing a regioregular polymer microstructure.
to the specified position of isotope labeled (15N) nitrogen. On
the other hand, if the mode of monomer insertion is random, a
regioirregular polymer structure forms, which would result in at
RESULTS AND DISCUSSION
■
Determination of Regioregularity in an Alkyne
Polycarbodiimide, Poly-1, through 15N NMR Spectros-
least two separate peaks in 15N NMR spectra of the polymer
due to a random distribution of the isotope labeled nitrogen to
imine and amine positions along the polymer chain.16,38
Figure 2 shows the 15N NMR spectrum of Poly-1 collected
in deuterated chloroform. The spectrum shows just a single
peak at 13.9 ppm (relative to external reference 15N-benzamide
set at 0.00 ppm), which is indicative of a highly regioregular
polymer structure ensuing from this polymerization.
copy. 15N isotope labeled alkyne polycarbodiimide Poly-1 has
been synthesized from its corresponding 15N labeled
carbodiimide monomer 8 as shown in Scheme 1.
Monomer 8 was prepared in five steps starting from
commercial heptanoyl chloride 1. 15N-enriched (99%)
ammonium chloride was used to synthesize 15N labeled n-
hexylamine hydrochloride 4 in three steps following the
literature procedure.16,19 In a separate reaction, commercial 3-
aminophenylacetylene 5 was converted into corresponding
isothiocyanate 6 using thiophosgene in the presence of
triethylamine using the literature procedure20 with a slight
modification. Thiourea derivative 7, obtained from combination
of 7 and 6, was treated with dibromotriphenylphosphorane in
the presence of triethylamine to form monomer 8. Monomer 8
was polymerized to Poly-1 using R-BINOL Ti(IV) diisoprop-
oxide21−23 catalyst at room temperature inside a glovebox
under a nitrogen atmosphere.
Furthermore, this specific regioisomer in the repeat units of
polymer with n-hexyl group bonded to amine nitrogen, and
therefore, the phenylacetylene group bonded to the imine
nitrogen was assigned based on FTIR spectral results. The
absence of isotopic shifts in the imine absorption in IR
spectrum (spectra available in Supporting Information) of
Poly-1 precludes the 15N labeled nitrogen at the imine position.
In addition, the observed chemical shift of the peak on 15N
NMR spectra is inconsistent with the literature report for the
regioisomer specified.16
During polymerization, if the mode of monomer insertion is
uniform, the resulting polymer will be homogeneous with
regioregular polymer chains. 15N NMR spectra of such
regioregular polymer would result in a single resonance due
Orthogonal and Site-Specific Pendant Group Mod-
ification. With established regioregular microstructure, Poly-1
is a foundational helical polymer from which functional
8160
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
macromolecules can be derived for potential applications. It is
noteworthy that all the previously reported functional
derivatives of Poly-1 with carboxylic acids, protected amines,
triazoles, and amino acids in the side chains13 introduced to the
pendant groups are now confirmed uniformly regioregular and
new appended functionalities bonded exclusively to imine
nitrogen site along the polymer chains. Therefore, these
polymer derivatives can be considered as perfectly alternating
functional polymers.
groups. This facile and quantitative modification of alkyne side
chains in Poly-3 as in previously reported Poly-1 demonstrates
that alkyne functionalities either bonded to helical polymer
backbone via a rigid aromatic tether (Poly-1) or through
flexible aliphatic linker (Poly-3) in repeat units are exposed and
easily accessible to the reagents. In addition, highly regioregular
structures of Poly-1 and Poly-2 coupled with close structural
similarities of Poly-3 with the mentioned polymers suggests a
regioregular polymer structure of Poly-3 with the aliphatic
alkyne group bonded to amine nitrogen in the repeat unit.
To double the potential appendable functional groups in the
repeat unit along the polymer chain, Poly-4 (Figure 3) has two
modifiable alkyne groups per repeat unit. Although the natures
of the two alkyne functionalities are different, phenylacetylene
and aliphatic alkyne, a selective modification of one alkyne
group over the other through “click” chemistry to incorporate
two different moieties is not possible in our hands. Therefore,
one of the two terminal alkyne groups needs to be rendered
inactive for a controlled postfunctionalization.
In order to alter the position of modifiable alkyne groups
along the polymer chain, we installed an alkyne group at a
remote carbon in the repeat unit of Poly-3 (Figure 3 and
One of the versatile approaches for orthogonal modification
of two alkyne functionalities is to use protection chemistry to
mask the activities of one of them. Here, we use a well-known
alkyne protecting group, trimethylsilyl (TMS), early in the
synthesis of Poly-5. Our initial attempt to synthesize an
asymmetric polycarbodiimide with two independently modifi-
able alkyne functionalitiesa propargyl group and a TMS
protected phenylacetylene in repeat unitremains unsuccess-
ful. In an attempted synthesis, a TMS protected 3-amino-
phenylacetylene 9a, obtained from Sonogashira coupling
reaction of 3-iodoaniline and trimethylsilylacetylene,17 was
treated with thiophosgene in the presence of triethylamine as
shown in Scheme 2 to obtain a thioisocyanate derivative 10a.
The thiourea derivative formed upon reaction of 10a with
propargylic amine is unstable and undergoes in-situ intra-
molecular cyclization, resulting in a heterocyclic compound 11
which is comparable to that of the synthesis of heterocyclic
derivatives reported by Arya et al.28 Use of isocyanate, instead
of thioisocyanate, would result in a stable urea derivative as
carbodiimide monomer precursor. However, the corresponding
isocyanate was unstable during aqueous work-up in the
attempted synthesis.
In order to overcome this intramolecular cyclization, a higher
homologue of alkynylamine, 6-amino-hex-1-yne 12, was
synthesized18 and used to prepare the thiourea derivative 13a
(Scheme 3). The subsequent protodesulfurization of thiourea
13a using dibromotriphenylphosphorane in the presence of
triethylamine generated carbodiimide monomer 14a. Monomer
14a was polymerized under the standard carbodiimide
polymerization conditions to obtain Poly-5 (Scheme 3).
The “click” conditions employed for Poly-3 were also used in
the postmodification of Poly-5 with commercial benzyl azide.
Benzyl azide was chosen once again because it would provide
Figure 3. A family of alkyne polycarbodiimides, Poly-1 and Poly-3;
dialkynes, Poly(4−6); alkenyl, Poly-7 and alkene-alkyne, Poly-10.
Previously reported Poly-2 is shown for comparison.
Scheme S2). The unprotected terminal alkyne functionality in
Poly-3 linked to the polymer backbone by a longer
hydrophobic tether allows synthetic versatilities to obtain
regioregular functional polycarbodiimide derivatives. We
employed CuAAC (“click”) protocol24−27 with optimized
conditions for polycarbodiimides13 in Poly-3. Click chemistry
was chosen because of its proven compatibility and efficiency in
alkyne polycarbodiimides. The CuAAC reaction of Poly-3 with
benzyl azide and the characterization of the purified polymer
product by 1H NMR showed the loss of 1H NMR signal at 1.90
ppm from terminal alkyne proton. In addition, FTIR analysis of
the product showed a complete disappearance of IR signals at
3297 cm−1 (s), corresponding to terminal alkyne C−H and
2115 cm−1 attributed to carbon−carbon triple bond in alkyne
Scheme 2. Attempted Synthesis of a Dialkyne Thiourea
8161
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
Scheme 3. Synthesis of Monoprotected Dialkyne Polymers Poly-5 and Poly-6
Scheme 4. Orthogonal Functionalization of Alkyne Pendant Groups in Sequential Click Reactions
1
signals in H NMR and IR spectroscopies in the product
without any interference from the signals in the parent polymer
molecule. Despite protection of the terminal alkyne function-
ality in phenylacetylene, CuAAC reaction in Poly-5 did not
show any selectivity on reactivity of the two alkynes. The lack
of selectivity is most possibly because of DBU-promoted
cleavage of acetylenic TMS group.29 The use of triethylamine as
a base in the click reaction instead of DBU gave mono click
product while retaining the TMS protected alkyne intact, albeit
at a slower rate.
M diethanolamine in THF was used as a mobile phase to
reduce the affinity of these polymers toward conventional SEC
column matrix.6,14 Molecular weight and molecular weight
distribution of new polymers are as follows: (a) Poly-1, Mw =
17 000 Da, Mn = 8007 Da, Mw/Mn = 2.13, (b) Poly-3, Mw = 20
000 Da, Mn = 8112 Da, Mw/Mn = 2.49, (c) Poly-5, Mw = 23
000 Da, Mn = 9340 Da, Mw/Mn = 2.50, and (d) Poly-6, Mw =
24 000 Da, Mn = 8182, Mw/Mn = 3.0.
Scheme 4 shows postmodification of Poly-6 in a series of
chemical transformations. To begin with, CuAAC reaction was
performed with benzyl azide (1.2 equiv relative to polymer
repeat unit) in the presence of CuI and DBU at room
temperature. FTIR analysis of the purified product Poly-7
showed the absence of strong IR signal at 3313 cm−1 attributed
to terminal alkyne C−H, demonstrating that all the terminal
alkynes were modified (Figure 4). Furthermore, with persistent
IR peak at 2152 cm−1, Figure 4 also illustrates that the TIPS
protected alkynes remain intact under these conditions.
Therefore, the alkyne functionalities in the repeat unit of
Poly-6 were modified in a control fashion in the first step
postmodification. The product polymer was characterized by
1H NMR and FTIR spectroscopies.
To move forward to be able to carry out control
postmodification reactions in dialkyne polymers, a more robust
alkyne-protecting group of similar category for clean depro-
tection was sought. Triisopropylsilyl (TIPS) protected alkynes
have been reported to be more robust compared to TMS
alkynes in “click reactions”.30 Therefore, the TIPS group was
then selected to protect one of the alkyne groups early in the
synthesis. Similar to Scheme 2, TIPS protected phenylacetylene
9b was converted into the corresponding isothiocyanate 10b
that in combination with 6-aminohex-1-yne (12) formed
thiourea derivative 13b (Scheme 3). The protodesulfurization
of the thiourea derivative using PPh3Br2 in the presence of
triethylamine resulted in monomer 14b. When polymerized,
monomer 14b furnished a TIPS alkyne polycarbodiimide, Poly-
6.
As shown in Scheme 4, once Poly-7 was obtained from the
first step click reaction, the alkyne protecting group (TIPS) was
removed using TBAF, a standard deprotecting reagent,31 to
access a second modifiable conjugation site as a phenyl-
acetylene group in the repeat unit in Poly-8. The complete
deprotection was confirmed by the appearance of the
characteristic IR signal at 3293 cm−1 corresponding to alkyne
These newly synthesized polymers were characterized by 1H
NMR, 13C NMR, FTIR, and polarimetry. Size exclusion
chromatography was employed to determine the molecular
weight of these polymers relative to polystyrene standards. 0.12
8162
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
cules, this approach can be extended to incorporate variety of
functionalities to optimize polymer properties.
In order to expand the diversity of functionalities that can be
incorporated in the side chains of polycarbodiimides and
further be explored in postmodification reactions, we
synthesized Poly-10 (Figure 3) with 4-vinylbenzene and 1-
hexyne in the repeat unit. Prior to the synthesis of Poly-10, the
compatibility of 4-vinylbenzene moiety in the standard
carbodiimide polymerization system was tested via the
synthesis of Poly-7 (Figure 3), a polymer with 4-vinylbenzene
and n-hexyl groups in the side chains (Scheme S3). This newly
incorporated vinyl functionality in the side chain offers new
conjugation reactions for further functionalization of the
polymer,32 especially, conjugation with thiols through thiol−
ene click chemistry.33−36 Further, alkyne−azide click and thiol−
ene click are known orthogonal reactions in macromole-
cules.33,37 However, to our knowledge, this orthogonal double
click chemistry has not yet been explored when applied to the
side chains of synthetic helical polycarbodiimides. This
orthogonal click approach delivers a higher degree of versatile
functionalization compared to functional chain-end polymers.
The presence of two pendant groups per repeat unit in
polycarbodiimides coupled with the compatibility of both the
terminal alkyne and vinyl functionalities in the polymerization
reaction lead to the synthesis of Poly-10 (Scheme 5).
As shown in Scheme 5, the synthesis of Poly-10 was
accomplished in short synthetic route. In brief, isothiocyanate
15 was combined with amine 12 to obtain a thiourea derivative
16 that resulted in monomer 17 upon treating with PPh3Br2/
Et3N. Monomer 17 was then polymerized to Poly-10 under the
standard carbodiimide polymerization conditions. The presence
of two known versatile groupsvinyl and alkyne functionalities
in the repeat unit of Poly-10opens up new opportunities to
employ two different well-known click chemistriesazide−
alkyne click and thiol−ene clickin a consecutive manner for
new functional polycarbodiimides in a short synthetic route.
The efficiency of this new polymer, Poly-10 in CuAAC click
reaction was tested and has been found to be facile as observed
in 1H NMR and FTIR spectra of the product (spectra included
in Supporting Information). The polymer after click reaction
(Poly-11) was further modified in a thiol−ene reaction (using
the literature procedure as described in ref 33) with
Figure 4. FTIR spectra of Poly-6 (1), Poly-7 (2, after click reaction),
and Poly-8 (3, after removal of TIPS groups).
C−H as shown in Figure 4. In addition, the 1H NMR spectrum
showed the loss of resonance signals from methyl protons on
TIPS group at ca. 1.0 ppm and the appearance of resonance at
ca. 2.96 ppm corresponding to phenylacetylene proton. In
addition to 1H NMR and FTIR, the resulting polymer (Poly-8)
was also analyzed by polarimetry. Poly-8 has specific optical
21
rotation [α]589 = 117° (c = 0.2 in CHCl3, l = 0.5), which is
21
comparable to its parent polymer Poly-6, [α]589 = 125° (c =
0.22 in CHCl3, l = 0.5).
The reactivity of phenylacetylene group in Poly-8 in CuAAC
click reaction was tested through incorporation of Boc-amine as
an example of second appended group in the repeat unit in
postmodification. This second step click reaction to obtain
Poly-9 took place in relatively short period of time (monitored
by IR signals) as compared to the first one. The sequential click
reaction in Poly-6 involving benzyl azide and Boc-amine is the
first example and a significant progress toward enriching
polycarbodiimide side chains with two dissimilar molecules in
postmodification. With desired functionalities in azide mole-
Scheme 5. Synthesis of Poly-10 with Alkyne and Vinyl Functionalities and Modification of Its Side Chains by CuAAC and
Thiol−Ene Click Reactions
8163
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
mercaptoethanol to functionalize side chains in our polymer
and study a new method to functionalize polycarbodiimides.
One of the most commonly used radical-mediated thiol−ene
reaction using azobis(isobutyronitrile) (AIBN) at elevated
temperature was attempted first. However, the attempted
AIBN-mediated thio−ene reaction at the elevated temperatures
(ca. 80 °C) for the extended reaction times (ca. 15 h) caused
the polymer to decompose back to the carbodiimide monomer
due to the thermal decomposition of polycarbodiimides that is
accelerated by common radical initiators. In order to overcome
this limitation, a photochemical approach was employed. This
later approach for thiol−ene reaction using the protocol
described in ref 33 ensued without complication and yielded
the polymer with newly appended alcohol functionalities in
Poly-12.
Chemistry for all HRMS data. We thank Dr. Sabapathy Sankar
for his help in 15N NMR spectroscopy. Our special thanks to
Dr. Mihaela C. Stefan and Dr. Prakash Sista, Department of
Chemistry, The University of Texas at Dallas, for their help in
performing GPC on these polymers.
REFERENCES
■
(1) Nakano, T.; Okamoto, Y. Chem. Rev. 2001, 101, 4013−4038.
(2) Yashima, E.; Maeda, K.; Iida, H.; Furusho, Y.; Nagai, K. Chem.
Rev. 2009, 109, 6102−6211.
(3) Chen, B.; Deng, J.; Cui, X.; Yang, W. Macromolecules 2011, 44,
7109−7114.
(4) Kennemur, J. G.; Novak, B. M. Polymer 2011, 52, 1693−1710.
(5) Kawauchi, T.; Kitaura, A.; Kawauchi, M.; Takeichi, T.; Kumaki, J.;
Iida, H.; Yashima, E. J. Am. Chem. Soc. 2010, 132, 12191−12193.
(6) Arnold, L.; Marx, A.; Thiele, C.; Reggelin, M. Chem.Eur. J.
2010, 16, 10342−10346.
(7) Green, M. M.; Park, J. W.; Sato, T.; Teramoto, A.; Lifson, S.;
Selinger, R. L. B.; Selinger, J. V. Angew. Chem., Int. Ed. 1999, 38, 3139−
3154.
CONCLUSIONS
■
An 15N isotope labeled alkyne polycarbodiimide, poly(N-(3-
ethynylphenyl)-15N′-hexyl)carbodiimide, has been synthesized
to study the polymer microstructure with a focus on its
regioregularities. 15N NMR spectroscopy illustrated a highly
regioregular distribution of pendant groups along the polymer
chain with n-hexyl group bonded to amine nitrogen and the
phenylacetylene group bonded to imine nitrogen of the repeat
unit. Additionally, two independently modifiable alkyne
moieties have been incorporated in the repeat unit of an
optically active alkyne polycarbodiimide, Poly-6. Orthogonal
postmodification of these alkyne groups have been performed
in consecutive click reactions, demonstrating that two different
sets of groups can be incorporated in repeat units of
polycarbodiimides in a controlled fashion under mild reaction
conditions using this protocol. Furthermore, a combination of
alkyne and vinyl groups in the side chains of a polycarbodiimide
has been introduced via the synthesis of Poly-10 that provided
an opportunity to employ sequential alkyne−azide and thiol−
ene click reactions for new functional polycarbodiimides
derivatives. This report on determining the regioregularity of
a helical polycarbodiimide and orthogonal side chain
modulation in polycarbodiimide system presents a significant
advancement and opens up the possibilities for precise
functional helical macromolecules that possess perfectly
alternating structures.
(8) Miyabe, T.; Hase, Y.; Iida, H.; Maeda, K.; Yashima, E. Chirality
2009, 21, 44−50.
(9) Tang, H.; Boyle, P.; Novak, B. J. Am. Chem. Soc. 2005, 127,
2136−2142.
(10) Kennemur, J. G.; Clark, J. B.; Tian, G.; Novak, B. M.
Macromolecules 2010, 43, 1867−1873.
(11) Xue, Q. B.; Kimura, T.; Fukuda, T.; Shimada, S.; Matsuda, H.
Liq. Cryst. 2004, 31, 137−143.
(12) Kim, J.; Novak, B. M.; Waddon, A. Macromolecules 2004, 37,
8286−8292.
(13) Budhathoki-Uprety, J.; Novak, B. M. Macromolecules 2011, 44,
5947−5954.
(14) Budhathoki-Uprety, J.; Peng, L.; Melander, C.; Novak, B. M.
ACS Macro Lett. 2012, 1, 370−374.
(15) Kennemur, J. G.; DeSousa, J. D.; Martin, J. D.; Novak, B. M.
Macromolecules 2011, 44, 5064−5067.
(16) DeSousa, J. D.; Novak, B. M. ACS Macro Lett. 2012, 1, 672−
675.
(17) Miyamura, Y.; Kinbara, K.; Yamamoto, Y.; Praveen, V.; Kato, K.;
Takata, M.; Takano, A.; Matsushita, Y.; Lee, E.; Lee, M.; Aida, T. J.
Am. Chem. Soc. 2010, 132, 3292−3294.
(18) Crivello, A.; Nervi, C.; Gobetto, R.; Crich, S.; Szabo, I.; Barge,
A.; Toppino, A.; Deagostino, A.; Venturello, P.; Aime, S. J. Biol. Inorg.
Chem. 2009, 14, 883−890.
(19) Huang, H.; Seid, M.; Keillor, J. J. Org. Chem. 1997, 62, 7495−
7496.
(20) Nowick, J.; Powell, N.; Nguyen, T.; Noronha, G. J. Org. Chem.
1992, 57, 7364−7366.
ASSOCIATED CONTENT
* Supporting Information
Further experimental details, NMR and IR spectra of
synthesized molecules. This material is available free of charge
via the Internet at http://pubs.acs.org.
■
S
(21) Balsells, J.; Davis, T.; Carroll, P.; Walsh, P. J. Am. Chem. Soc.
2002, 124, 10336−10348.
(22) Tian, G.; Lu, Y.; Novak, B. M. J. Am. Chem. Soc. 2004, 126,
4082−4083.
(23) Tang, H.; Garland, E.; Novak, B. M.; He, J.; Polavarapu, P.; Sun,
F.; Sheiko, S. Macromolecules 2007, 40, 3575−3580.
(24) Kolb, H.; Finn, M.; Sharpless, K. Angew. Chem., Int. Ed. 2001,
40, 2004−2021.
AUTHOR INFORMATION
Corresponding Author
*E-mail: bruce.novak@utdallas.edu.
Notes
■
(25) Binder, W.; Sachsenhofer, R. Macromol. Rapid Commun. 2007,
28, 15−54.
The authors declare no competing financial interest.
(26) Fournier, D.; Hoogenboom, R.; Schubert, U. Chem. Soc. Rev.
2007, 36, 1369−1380.
(27) Lutz, J. Angew. Chem., Int. Ed. 2007, 46, 1018−1025.
(28) Arya, V.; Grewal, R.; Kaul, C.; David, J.; Honkan, V. Indian J.
Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1977, 15, 133−140.
(29) Yeom, C.; Kim, M.; Choi, W.; Kim, B. Synlett 2008, 4, 565−568.
(30) Cuevas, F.; Oliva, A.; Pericas, M. Synlett 2010, 12, 1873−1877.
(31) Malkoch, M.; Thibault, R.; Drockenmuller, E.; Messerschmidt,
M.; Voit, B.; Russell, T.; Hawker, C. J. Am. Chem. Soc. 2005, 127,
14942−14949.
ACKNOWLEDGMENTS
■
Funding was provided by the Faculty Start up from The
University of Texas at Dallas (UTD), the Endowed Chair for
Excellence at UTD, and the Howard J. Schaeffer Distinguished
Chair at NCSU. We thank NCSU Department of Chemistry
Mass Spectrometry Facility funded by the North Carolina
Biotechnology Center and the NCSU Department of
8164
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165

Macromolecules
Article
(32) Lu, H.; Bai, Y.; Wang, J.; Gabrielson, N.; Wang, F.; Lin, Y.;
Cheng, J. Macromolecules 2011, 44, 6237−6240.
(33) Campos, L. M.; Killops, K. L.; Sakai, R.; Paulusse, J. M. J.;
Damiron, D.; Drockenmuller, E.; Messmore, B. W.; Hawker, C. J.
Macromolecules 2008, 41, 7063−7070.
(34) Hoyle, C. E.; Bowman, C. N. Angew. Chem., Int. Ed. 2010, 49,
1540−1573.
(35) Kade, M. J.; Burke, D. J.; Hawker, C. J. J. Polym. Sci., Part A:
Polym. Chem. 2010, 48, 743−750.
(36) Sumerlin, B. S.; Vogt, A. P. Macromolecules 2010, 43, 1−13.
(37) Iehl, J.; Nierengarten, J. Chem. Commun. 2010, 46, 4160−4162.
(38) Reuther, J. F.; DeSousa, J. D.; Novak, B. M. Macromolecules
2012, DOI: 10.1021/ma301448b.
8165
dx.doi.org/10.1021/ma301639m | Macromolecules 2012, 45, 8155−8165