Synthesis and helical properties of N-substituted p-benzamide random copolymers possessing chiral/achiral and (S)/(R) side chains

Article abstract of DOI:10.1002/pola.24559

Random copolymers of poly(p-benzamide)s having a methyl-substituted tri(ethylene glycol) unit as a chiral side chain and a nonsubstituted tri(ethylene glycol) or branching alkyl unit as an achiral side chain were synthesized by copolymerization of N-substituted 4-aminobenzoic acid ester monomers with a base in the presence of an initiator. Copolymerizations of the chiral (S)-monomer with N-tri(ethylene glycol) achiral monomer and with the racemic monomer were carried out by the addition of a mixture of two monomers and an initiator to a solution of a base all at once, affording the corresponding random copolymers. On the other hand, random copolymerization of the chiral monomer with monomer having an achiral branching alkyl side chain required dropwise addition of the achiral monomer to a mixture of the chiral monomer, the initiator, and the base. These copolymers formed helical structures, but analysis of the CD spectra indicated the absence of cooperativity between the monomer units along the copolymers.

Full text of DOI:10.1002/pola.24559

Synthesis and Helical Properties of N-Substituted p-Benzamide Random
Copolymers Possessing Chiral/Achiral and (S)/(R) Side Chains
AKIHIRO YOKOYAMA, YUKO INAGAKI, TOMOMI ONO, TSUTOMU YOKOZAWA
Department of Material and Life Chemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku,
Yokohama 221-8686, Japan
Received 13 November 2010; accepted 21 December 2010
DOI: 10.1002/pola.24559
Published online 18 January 2011 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Random copolymers of poly(p-benzamide)s having
a methyl-substituted tri(ethylene glycol) unit as a chiral side
chain and a nonsubstituted tri(ethylene glycol) or branching
alkyl unit as an achiral side chain were synthesized by
copolymerization of N-substituted 4-aminobenzoic acid ester
monomers with a base in the presence of an initiator. Copoly-
merizations of the chiral (S)-monomer with N-tri(ethylene gly-
col) achiral monomer and with the racemic monomer were
carried out by the addition of a mixture of two monomers and
an initiator to a solution of a base all at once, affording the cor-
responding random copolymers. On the other hand, random
copolymerization of the chiral monomer with monomer having
an achiral branching alkyl side chain required dropwise addi-
tion of the achiral monomer to a mixture of the chiral mono-
mer, the initiator, and the base. These copolymers formed
helical structures, but analysis of the CD spectra indicated the
absence of cooperativity between the monomer units along
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the copolymers.
2011 Wiley Periodicals, Inc. J Polym Sci
Part A: Polym Chem 49: 1387–1395, 2011
KEYWORDS: CD spectroscopy; copolymerization; cooperative
effects; helix; polyamides
INTRODUCTION Helical polymers and oligomers have been
attracting increasing attention from both structural and func-
tional points of view. Most artificial helical polymers
reported so far can be categorized as static or dynamic heli-
cal polymers.1–4 As exemplified by polyisocyanides5,6 and
polymethacrylates1,7 with bulky side chains, helical struc-
tures of static helical polymers are rigid and stable, without
conformational change at room temperature, due to high he-
lix inversion barriers. On the other hand, helical polymers
possessing low helix inversion barriers, such as polyisocya-
nates,8,9 polysilanes,10,11 and polyacetylenes,12–16 show
dynamic helical properties. In these polymers, helical rever-
sal can occur, and the helical sense is controlled thermody-
namically. One of the unique features of dynamic helical
polymers is chiral amplification. When the monomer units of
dynamic helical polymers interact cooperatively with each
other, a small chiral bias can induce a large excess of helical
sense. This phenomenon was intensively studied by Green
et al. using polyisocyanates.9 The chiral amplification,
observed in copolymers composed of chiral and achiral
monomer units, is called the ‘‘sergeants and soldiers’’
effect,17 whereas ‘‘majority rules’’ applies to the chiral ampli-
fication of copolymers composed of (R)- and (S)-enantio-
meric monomer units.18 The ‘‘sergeants and soldiers’’ effect
was observed not only in helical polymers but also in heli-
cally folded oligomers.19
In the course of our study of chain-growth condensation
polymerization,20,21 we found that poly(p-benzamide)s bear-
ing a chiral tri(ethylene glycol) side chain as an N-substitu-
ent adopt a helical conformation with three monomer units
per turn in solution.22 Variable-temperature CD study
showed that the CD intensity decreased with increase of
temperature, indicating thermodynamically controlled helical
character of this polyamide. The helical structure arises from
the cis preference of N-substituted aromatic amide linkage23
and syn arrangement of the three consecutive benzene units
connected by two amide linkage.24,25
To elucidate the helical folding of this aromatic polyamide,
we focused on the cooperativity of the monomer units. For
the precise evaluation of monomer cooperativity according
to the ‘‘sergeants and soldiers’’ and ‘‘majority rules’’ effects, it
is important to prepare copolymers with a random sequence
of chiral/achiral or (R)/(S) monomer units. We report herein
the synthesis of random copolymers of poly(p-benzamide)s
possessing chiral/achiral (1,2) and (R)/(S) (3) side chains,
and the results of ‘‘sergeants and soldiers’’ experiments with
1 and 2 and a majority rules experiment with 3 (Chart 1).
The copolymers 1–3 possess a (S)-2-[2-(2-methoxyethoxy)e-
thoxy] propyl side chain as a chiral pendant group, the same
chiral side chain as in the helical poly(p-benzamide) that we
reported previously.22 To examine the steric effects of side
chains on the copolymerization behavior of chiral and achiral
Correspondence to: A. Yokoyama (E-mail: yokoyama@kanagawa-u.ac.jp) or T. Yokozawa (E-mail: yokozt01@kanagawa-u.ac.jp)
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Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 49, 1387–1395 (2011) 2011 Wiley Periodicals, Inc.
N-SUBSTITUTED p-BENZAMIDE RANDOM COPOLYMERS, YOKOYAMA ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
each polymer solution for CD experiments was adjusted so
that the absorbance at 300 nm was 1.0.
Materials
Commercially available dehydrated dichloromethane (Kanto),
THF (stabilizer-free, Kanto), and N,N-dimethylformamide
(Wako) were used as dry solvents. Hexamethylphosphora-
mide (HMPA) was distilled before use. The other compounds,
including 1.0-M lithium hexamethyldisilazide (LiHMDS) in
THF (Aldrich) and 1-M borane–THF complex in THF (Kanto),
were used as received. The monomers (S)-522 and 626 and
the initiator 427 were synthesized according to the reported
procedures. The monomers 7 and racemic 5 were synthe-
sized as described below.
Synthesis of Monomers
The monomer 7 was synthesized as illustrated in Scheme 1.
Amide 8
A solution of 2-propylpentanoic acid (4.34 g, 30.1 mmol) in
thionyl chloride (23.5 mL, 324 mmol) was stirred at room
temperature overnight. Then, the mixture was concentrated
under reduced pressure, and the residue was dissolved in
dry CH2Cl2 (30 mL). This solution was added dropwise
under a nitrogen atmosphere to a solution of phenyl 4-ami-
nobenzoate28 (4.80 g, 22.5 mmol) and triethylamine (4.2 mL,
25 mmol) in dry CH2Cl2 (82 mL) with stirring at 0 ꢀC, and
the mixture was further stirred at room temperature for 5 h.
Water was added, and the mixture was extracted with
CH2Cl2. The organic layer was washed with water and satu-
rated aqueous Na2CO3, dried over anhydrous MgSO4, and
concentrated under reduced pressure. Recrystallization of
the residue from methanol afforded 8 as colorless needles
CHART 1 Chiral/achiral copolymers (1,2) and (R)/(S) copolymer
(3).
monomers and on the helical properties of the copolymers, a
tri(ethylene glycol) monomethyl ether unit and a 2-propyl-
pentyl unit were used as achiral pendants for the copoly-
mers 1 and 2, respectively.
EXPERIMENTAL
General Considerations
ꢀ
(6.03 g, 79%). mp 173.0–176.0 C.
1H and 13C NMR spectra were obtained on JEOL ECA-500
and ECA-600 spectrometers, and the internal standards for
1H and 13C NMR spectra were tetramethylsilane (0.00 ppm)
and the midpoint of CDCl3 (77.00 ppm), respectively. IR
spectra were recorded on a JASCO FT/IR-410. All melting
points were measured with a Yanagimoto hot stage melting
point apparatus without correction. Column chromatography
was performed on silica gel (Kieselgel 60, 70–230, and 230–
400 mesh, Merck) with a specified solvent. The conversion
of monomers during polymerization was determined by
reversed-phase HPLC using a JASCO Finepak SIL C18S col-
umn. In the copolymerization of (S)-5 and rac-5, conversion
of each enantiomeric monomer was determined by chiral
stationary phase HPLC using Daicel Chiralpack AD-H. The Mn
and Mw/Mn values of polymers were measured on a Shodex
GPC-101 equipped with Shodex UV-41 and Shodex RI-71S
detectors and two Shodex KF-804L columns (bead size ¼ 7
lm, pore size ¼ 200 Å). Tetrahydrofuran (THF) was used as
the eluent (temperature ¼ 40 ꢀC, flow rate ¼ 2 mL/min).
Calibration was carried out using polystyrene standards. Iso-
lation of polyamides was carried out with a Japan Analytical
Industry LC-908 Recycling Preparative HPLC (eluent: chloro-
form) with the use of two TOSOH TSK-gel columns (2 ꢁ
G2000HHR). UV–vis spectra were measured on a Shimadzu
UV-1800 spectrometer. CD spectra were measured on a
JASCO J-600 using a 10-mm quartz cell. The concentration of
1H NMR (500 MHz, CDCl3, d, ppm): 8.14 (d, J ¼ 8.9 Hz, 2H),
7.72 (br s, 1H), 7.70 (d, J ¼ 8.9 Hz, 2H), 7.41 (t, J ¼ 7.9 Hz,
2H), 7.26 (t, J ¼ 7.4 Hz, 1H), 7.20 (d, J ¼ 7.4 Hz, 2H), 2.28–
2.23 (m, 1H), 1.74–1.66 (m, 2H), 1.51–1.44 (m, 2H), 1.41–
1.31 (m, 4H), 0.92 (t, J ¼ 7.3 Hz, 6H). 13C NMR (126 MHz,
CDCl3, d, ppm): 175.1, 164.8, 150.9, 142.8, 131.4, 129.4,
125.8, 124.6, 121.7, 119.0, 48.8, 35.2, 20.8, 14.1. IR (KBr,
cmꢂ1): 3296, 2955, 2930, 1731, 1660, 1525, 1276, 1199,
1079, 743, 691.
Monomer 7
A two-necked round-bottomed flask, equipped with a three-
way stopcock and a refluxing condenser, was heated under
SCHEME 1 Synthesis of the monomer 7.
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ARTICLE
SCHEME 2 Synthesis of the racemic monomer 5.
reduced pressure and cooled to room temperature under an
argon atmosphere. A 1.0 mol/L THF solution of borane–THF
complex (4.5 mL, 4.5 mmol) was added via a syringe from
the three-wꢀay stopcock under a stream of nitrogen and
stirred at 0 C. Then a solution of 8 (509 mg, 1.50 mmol) in
dry THF (4 mL) was added via a syringe from the three-way
stopcock under a stream of nitrogen, and the reaction mix-
ture was refluxed for 8 h under an argon atmosphere, cooled
to 0 ꢀC, and poured into ice-water. The mixture was
extracted with AcOEt, and the organic layer was washed
with water, dried over anhydrous Na2SO4, and concentrated
under reduced pressure. Purification by silica gel column
chromatography (AcOEt/hexane ¼ 1/9) gave the monomer 7
as a yellowish viscous oil (266 mg, 50%).
(neat, cmꢂ1): 2924, 2880, 1757, 1457, 1274, 1197, 1145,
1109, 1030, 740, 698.
Introduction of Methyl Group
Addition of reagents into the reaction flask was carried out
via a syringe from the three-way stopcock under a stream of
nitrogen. A round-bottomed flask, equipped with a three-way
stopcock, was heated under reduced pressure and cooled to
room temperature under an argon atmosphere. A 1.0 mol/L
THF solution of LiHMDS (19 mL, 19 mmol), HMPA (8 mL),
and dry THF (100 mL) was added, and the solution was
stirred at ꢂ78 ꢀC. To the cooled solution was added drop-
wise a solution of 9 (5.60 g, 20.9 mmol, azeotropically dried
with toluene before use) in dry THF (80 mL) over 3 h, and
then the mixture was stirred at –78 ꢀC for 30 min. Next,
iodomethane (6.2 mL, 99 mmol) was added, and the mixture
was further stirred at ꢂ78 ꢀC overnight. The reaction was
quenched by the addition of saturated aqueous NH4Cl, and
the mixture was extracted with AcOEt five times. The com-
bined organic layers were dried over anhydrous MgSO4 and
concentrated under reduced pressure. The crude product
was purified by silica gel column chromatography (AcOEt/
hexane ¼ 1/1) to yield 10 as a yellowish liquid (3.40 g,
57%).
1H NMR (600 MHz, CDCl3, d, ppm): 8.01 (d, J ¼ 8.9 Hz, 2H),
7.40 (t, J ¼ 8.6 Hz, 2H), 7.23 (t, J ¼ 7.6 Hz, 1H), 7.19 (d, J ¼
7.6 Hz, 2H), 6.59 (d, J ¼ 8.6 Hz, 2H), 4.23 (t, J ¼ 5.2 Hz, 1H),
3.09 (t, J ¼ 5.8 Hz, 2H), 1.69–1.65 (m, 1H), 1.40–1.30 (m,
8H), 0.92 (t, J ¼ 7.9 Hz, 6H). 13C NMR (151 MHz, CDCl3, d,
ppm): 165.3, 152.8, 151.3, 132.3, 129.3, 125.4, 121.9, 116.8,
111.3, 46.8, 37.2, 34.3, 19.8, 14.2. IR (neat, cmꢂ1): 3388,
2956, 2928, 2871, 1705, 1605, 1270, 1200, 742, 690.
The racemic monomer rac-5 was synthesized as illustrated
in Scheme 2.
1H NMR (500 MHz, CDCl3, d, ppm): 7.37–7.32 (m, 5H), 5.20
(d, J ¼ 12.3 Hz, 1H), 5.16 (d, J ¼ 12.3 Hz, 1H), 4.10 (q, J ¼
6.7 Hz, 1H), 3.77–3.73 (m, 1H), 3.68–3.58 (m, 5H), 3.53–3.51
(m, 2H), 3.37 (s, 3H), 1.43 (d, J ¼ 6.9 Hz, 3H). 13C NMR (126
MHz, CDCl3, d, ppm): 173.04, 135.63, 128.52, 128.26, 128.13,
75.26, 71.86, 70.53, 70.46, 69.47, 66.40, 58.95, 18.61. IR
(neat, cmꢂ1): 2927, 2877, 1587, 1498, 1455, 1372, 1267,
1197, 1123, 1030, 752, 699.
Benzyl Ester 9
The reaction was carried out according to the reported pro-
cedure.29 To a stirred solution of 2-[2-(2-methoxyethoxy)e-
thoxy]acetic acid (603 mg, 3.39 mmol) in dry CH2Cl2 (10
ꢀ
mL) at 0 C were added triethylamine (0.45 mL, 0.33 mmol),
benzyl chloroformate (0.44 mL, 3.1 mmol), and 4-(dimethyla-
mino)pyridine (36 mg, 0.30 mmol) in this sequence, and the
mixture was further stirred at 0 ꢀC for 30 min. Then, the
mixture was diluted with CH2Cl2, and washed with saturated
aqueous NaHCO3, 0.1 mol/L hydrochloric acid, and brine,
and the combined aqueous layers were extracted with
CH2Cl2. The organic layers were combined, dried over anhy-
drous MgSO4, and concentrated under reduced pressure. Pu-
rification with silica gel column chromatography (AcOEt/hex-
ane ¼ 1/1) afforded 9 as a colorless liquid (664 mg, 79%).
Carboxylic Acid 11
A mixture of 10 (3.30 g, 11.7 mmol) and 5% Pd-C (0.500 g)
in ethanol (68.5 mL) was stirred vigorously at room temper-
ature for 2 h under a H2 atmosphere. Then the reaction mix-
ture was filtered through Celite. Concentration of the filtrate
under reduced pressure gave 11 as an yellow oil (2.23 g,
99%).
1H NMR (500 MHz, CDCl3, d, ppm): 7.28 (br s, 1H), 4.07 (q, J
¼ 7.0 Hz, 1H), 3.81–3.76 (m, 1H), 3.73–3.65 (m, 5H), 3.60–
3.53 (m, 2H), 3.39 (s, 3H), 1.46 (d, J ¼ 7.0 Hz, 3H). 13C NMR
(126 MHz, CDCl3, d, ppm): 175.87, 75.53, 71.72, 70.54,
70.18, 69.77, 59.00, 18.39. IR (neat, cmꢂ1): 2930, 2618,
1739, 1456, 1373, 1291, 1244, 1201, 1121, 1027.
1H NMR (500 MHz, CDCl3, d, ppm): 7.39–7.31 (m, 5H), 5.19
(s, 2H), 4.20 (s, 2H), 3.76–3.74 (m, 2H), 3.71–3.68 (m, 2H),
3.65–3.63 (m, 2H), 3.55–3.53 (m, 2H), 3.37 (s, 3H). 13C NMR
(126 MHz, CDCl3, d, ppm): 170.31, 135.40, 128.56, 128.55,
128.38, 128.36, 71.85, 70.63, 70.50, 68.65, 66.46, 58.99. IR
N-SUBSTITUTED p-BENZAMIDE RANDOM COPOLYMERS, YOKOYAMA ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
Amide 12
Random Copolymerization of (S)-5 and 6
A solution of 11 (2.20 g, 11.4 mmol) in SOCl2 (1.8 mL, 25
mmol) was stirred at room temperature overnight. After addi-
tion of further SOCl2 (8.0 mL, 0.11 mol), stirring was contin-
ued at room temperature for 5 h, and then the mixture was
concentrated under reduced pressure. The residue was dis-
solved in dry CH2Cl2 (13 mL), and the solution was added
dropwise to a stirred solution of phenyl 4-aminobenzoate28
(2.50 g, 10.3 mmol) and ꢀtriethylamine (2.1 mL, 15 mmol) in
dry CH2Cl2 (37 mL) at 0 C under an argon atmosphere. This
mixture was stirred at room temperature for 19 h, water was
added, and the whole was extracted with CH2Cl2. The organic
layer was washed with water and saturated aqueous NaHCO3,
dried over anhydrous MgSO4, and concentrated under reduced
pressure. Purification of the crude product by silica gel col-
umn chromatography (AcOEt/hexane ¼ 3/2) gave 12 as pale
Into a flask were added (S)-5 (84.1 mg, 0.236 mmol), 6
(27.0 mg, 0.0787 mmol), and 4 (1.3 mg, 0.0060 mmol). The
mixture was dried azeotropically with toluene, and a solu-
tion of anthracene (5.5 mg, used as an internal standard for
estimation of monomer conversion) in dry THF (0.72 mL)
was added. Then, the solution was cooled to ꢂ10 ꢀC under
an argon atmosphere and added all at once to a 1.0-M solu-
tion of LiHMDS in THF (0.30 mL) with stirring at ꢂ10 ꢀC.
The reaction mixture was further stirred at ꢂ10 ꢀC, and
small amounts were withdrawn into a syringe during the
polymerization for the analysis of monomer conversion by
reversed-phase HPLC. After 3.5 h, saturated aqueous NH4Cl
was added. The mixture was extracted with CHCl3, and the
organic layer was washed with water and dried over anhy-
drous MgSO4. Purification by means of recycling preparative
HPLC afforded the copolymer 173/27 as a light yellow oil
(90.5 mg, quant).
ꢀ
yellow crystals (3.98 g, 96%). mp 68–71 C.
1H NMR (500 MHz, CDCl3, d, ppm): 9.12 (br s, 1H), 8.17 (d, J
¼ 8.9 Hz, 2H), 7.82 (d, J ¼ 8.9 Hz, 2H), 7.42 (t, J ¼ 7.5 Hz,
2H), 7.26 (t, J ¼ 7.5 Hz, 1H), 7.21 (d, J ¼ 7.4 Hz, 2H), 4.01
(q, J ¼ 6.9 Hz, 1H), 3.84–3.57 (m, 8H), 3.38 (s, 3H), 1.52 (d, J
¼ 6.7 Hz, 3H). 13C NMR (126 MHz, CDCl3, d, ppm): 172.16,
164.70, 150.99, 142.60, 131.27, 129.39, 125.73, 124.79,
121.72, 119.21, 76.92, 71.70, 70.73, 70.15, 69.68, 58.93,
18.75. IR (neat, cmꢂ1): 3294, 3076, 2924, 2871, 2857, 1726,
1655, 1560, 1529, 1459, 1317, 1259, 1203, 1118, 1073, 845,
745, 694, 519.
1H NMR (600 MHz, CD2Cl2, d, ppm): 7.07 (br, Ar-H), 6.94 (d,
J ¼ 7.5 Hz, Ar-H), 3.92 (br, ACH2CH2NA), 3.85–3.31 (m,
CH3O(CH2CH2O)2CH2CH2NA and CH3O(CH2CH2O)2CH(CH3)
CH2NA), 3.30–3.28 (m, CH3OA), 1.08 (d, J ¼ 4.8 Hz,
AOCH(CH3)CH2NA). GPC (THF, PS): Mn ¼ 9800, Mw/Mn
¼
1.08.
Random Copolymerization of (S)-5 and 7
by Dropwise Addition Method
Into a flask were added (S)-5 (86.7 mg, 0.243 mmol) and 4
(2.2 mg, 0.010 mmol). The mixture was dried azeotropically
with toluene, and a solution of anthracene (10.5 mg, used as
an internal standard for estimation of monomer conversion)
in dry THF (0.82 mL) was added. The mixture was cooled to
Racemic Monomer rac-5
The reaction was carried out as described for the synthesis
of 7, using a 1.0 mol/L THF solution of borane–THF complex
(12 mL, 14 mmol) and a solution of 12 (3.93 g, 9.79 mmol)
in dry THF (27 mL). After the reaction mixture had been
refluxed for 5 h, it was cooled to 0 ꢀC, and 6 mol/L hydro-
chloric acid (3 mL) was added. The mixture was refluxed for
1 h and cooled to room temperature. It was diluted with
water and neutralized with saturated aqueous NaHCO3 to pH
8 and then extracted with AcOEt. The organic layer was
washed with water, dried over anhydrous MgSO4, and con-
centrated. Purification of the residue with silica gel column
chromatography (AcOEt/hexane ¼ 1/1) afforded rac-5 as a
ꢀ
ꢂ10 C under an argon atmosphere and added all at once to
a 1.0 M solution of LiHMDS in THF (0.32 mL) with stirring
at ꢂ10 ꢀC. Then a solution of 7 (25.0 mg, 0.0729 mmol) in
dry THF (0.30 mL) was added dropwise over 3 h with
the aid of a syringe pump, and the mixture was stirred at
ꢂ10 ꢀC for 3 h. Sampling and purification were conducted
as described for the synthesis of 1, and 266/34 was obtained
as a light yellow oil (29 mg, 34%).
1H NMR (600 MHz, CDCl3, d, ppm): 7.11–6.76 (m, Ar-H),
3.91–3.40 (m, CH3O(CH2CH2O)2CH(CH3)CH2NA and (CH3CH2CH2)2
CHCH2NA), 3.34 (s, CH3OA), 1.53 (m, (CH3CH2CH2)2CHCH2NA),
1.29–1.10 (m, AOCH(CH3)CH2NA and (CH3CH2CH2)2CHCH2NA),
ꢀ
pale yellow solid (3.38 g, 93%). mp 62–66 C.
1H NMR (500 MHz, CDCl3, d, ppm): 8.00 (d, J ¼ 8.9 Hz, 2H),
7.40 (t, J ¼ 7.4 Hz, 2H), 7.22 (t, J ¼ 7.5 Hz, 1H), 7.19 (d, J ¼
7.5 Hz, 2H), 6.62 (d, J ¼ 8.9 Hz, 2H), 5.01 (br s, 1H), 3.80–
3.73 (m, 2H), 3.70–3.64 (m, 4H), 3.60–3.56 (m, 3H), 3.40 (s,
3H), 3.30–3.28 (m, 1H), 3.14–3.10 (m, 1H), 1.24 (d, J ¼ 6.0
Hz, 3H). 13C NMR (126 MHz, CDCl3, d, ppm): 165.54, 153.03,
151.55, 132.41, 129.47, 125.53, 122.12, 117.19, 111.86,
74.39, 72.14, 70.96, 70.69, 68.21, 59.20, 48.58, 18.02. IR
(neat, cmꢂ1): 3371, 3062, 2972, 2875, 1720, 1607, 1532,
1487, 1456, 1422, 1375, 1344, 1270, 1200, 1172, 1063, 999,
960, 838, 763, 745, 691.
0.78 (m, (CH3CH2CH2)2CHCH2NA). GPC (THF, PS): Mn
7900, Mw/Mn ¼1.05.
¼
Random Copolymerization of (S)- and (R)-5
Into a flask were added (S)-5 (84.9 mg, 0.238 mmol), rac-5
(30.5 mg, 0.0852 mmol), and 4 (2.2 mg, 0.010 mmol), and
the mixture was dried under reduced pressure at 50 ꢀC
overnight. A solution of naphthalene (16.1 mg, used as an in-
ternal standard for estimation of monomer conversion) in
dry THF (0.40 mL) was added. Then, the mixture was cooled
ꢀ
Polymerization
to ꢂ10 C under an argon atmosphere and added all at once
Addition of reagents to the reaction flask was carried out via
a syringe from the three-way stopcock under a stream of
nitrogen.
to a 0.5-M solution of LiHMDS in THF (0.30 mL) with stir-
ring at ꢂ10 ꢀC. The reaction mixture was further stirred at
ꢂ10 ꢀC, and small amounts were withdrawn into a syringe
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SCHEME 3 Synthesis of random copolymers 1 and 2.
during the polymerization for the analysis of monomer con-
version by reversed-phase HPLC. After 4.0 h, saturated aque-
ous NH4Cl was added. The mixture was extracted with
CHCl3, and the organic layer was washed with water and
dried over anhydrous MgSO4. Purification by means of recy-
cling preparative HPLC afforded the copolymer 387/13 as a
light yellow solid (55.4 mg, 64%).
was thought to be sufficiently random for a ‘‘sergeants and
soldiers’’ experiment. The Mn and Mw/Mn values and the chi-
ral unit ratios of the copolymers 1 isolated by preparative
HPLC are summarized in Table 1. The Mn values of the
obtained polymers were smaller than those based on the
feed ratios of the monomers to the initiator (13,800–
14,100), probably due to self-initiation of the monomers.31
GPC (THF, PS): Mn ¼ 6500, Mw/Mn ¼ 1.08.
Random Copolymerization with Achiral Monomer
Having a Branching Alkyl Side Chain
RESULTS AND DISCUSSION
The achiral monomer 7 with a branching alkyl side chain
and the chiral monomer (S)-5 were copolymerized with the
initial monomer feed ratio ([(S)-5]0/[7]0) of 75/25, by the
addition of a mixture of the two monomers and the initiator
4 to a solution of LiHMDS. However, the time-conversion
plot of this polymerization showed that the conversion of 7
was much faster than that of (S)-5, indicating the formation
of a block-like copolymer (Fig. 2). This result is consistent
with a previous report that the polymerization of 4-amino-
benzoic acid esters with an N-tri(ethylene glycol) substituent
is much slower than the polymerization of N-alkyl monomer
due to coordination of the lithium cation to the tri(ethylene
glycol) moiety.26
Random Copolymerization with Achiral Monomer
Having a Linear Side Chain
The synthesis of chiral/achiral random copolymers 1 and 2
was tried under chain-growth condensation polymerization
ꢀ
conditions in THF at –10 C using lithium 1,1,1,3,3,3-hexame-
thyldisilazide (LiHMDS) as a base and phenyl 4-methylben-
zoate (4) as an initiator (Scheme 3).30 According to our pre-
vious report, phenyl ester monomers were used instead of
methyl ester monomers to control the polymerization.26
For the synthesis of 1, the copolymerization of (S)-5 and 6
was carried out by the addition of a THF solution containing
4, (S)-5, and 6 to a THF solution of LiHMDS all at once.
Using 2 mol % of the initiator 4 and 1 equiv of LiHMDS to
the monomers, the initial monomer feed ratio ([(S)-5]0/[6]0)
was changed from 75/25 to 50/50 and 25/75, and the con-
versions of (S)-5 and 6, as well as the Mn and Mw/Mn values
of the growing polymers, were determined during the poly-
merizations by sampling of the reaction mixture at appropri-
ate intervals. These copolymerizations proceeded smoothly
to afford copolymers with Mn values of about 9000 before
purification. The Mw/Mn values of the growing polymers
were less than 1.15 during the polymerizations, suggesting a
chain-growth polymerization behavior of these copolymeriza-
tions. The relationships between the monomer conversion
and the monomer unit composition of the growing polymer
were examined so as to confirm randomness of the copoly-
merization (Fig. 1). In all three copolymerizations for the
synthesis of 1, the chiral unit ratio of polymers was lower
than the feed ratio of the chiral monomer at the initial and
middle stages of polymerization, slightly increased with the
progress of polymerization, and reached the initial feed ratio
at the final stage. The slightly slower conversion of the chiral
monomer (S)-5, compared with the achiral 6, presumably
arises from steric hindrance of the branching methyl group
in the chiral side chain of (S)-5, which would slow down the
amide-forming reaction. Although the chiral unit ratios were
not constant during the copolymerization, the change was
small, and the sequence of the chiral and achiral pendants
FIGURE 1 Plots of the chiral unit ratio of the growing copoly-
mers as a function of total conversion of monomers ((S)-5 and
6). Copolymerization of (S)-5 and 6 was carried out in the pres-
ence of 4 (([(S)-5]0 þ [6]0)/[4]0 ¼ 50) and LiHMDS (1.0 equiv to
the monomers) in THF at –10 ꢀC. The feed ratios of monomers
([(S)-5]0/[6]0) were 75/25 (circle), 50/50 (square), and 25/75
(triangle).
N-SUBSTITUTED p-BENZAMIDE RANDOM COPOLYMERS, YOKOYAMA ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
TABLE 1 Copolymerization of (S)-5 and 6 for the Synthesis of 1
Reaction Conditionsa
Feed ratio Reaction
Copolymer 1
Chiral/Achiral
Unit Ratioc
b
b
Entry
([(S)-5]0/[6]0)
Time (h)
1
Mn
Mw/Mn
1
2
3
a
75/25
50/50
25/75
3.5
3.0
2.3
173/27
143/57
122/78
9,800
8,900
9,000
1.08
1.05
1.06
73/27
43/57
22/78
Copolymerization of (S)-5 and 6 was carried out in the presence of 2 mol% of 4 and 1.0 equivalent of
LiHMDS to the monomers in THF at ꢂ10 ꢀC.
b
Determined by GPC based on polystyrene standards (eluent: THF).
c
Determined by 1H NMR in CDCl3.
To synthesize the copolymer 2 in which the two monomer
(Table 2). During these two copolymerizations, the mono-
mers (S)-5 and 7 were converted at a similar rate to that in
the case of [(S)-5]0/[7]0 at the ratio of 75/25, indicating the
formation of random copolymers. In all the copolymeriza-
tions, the chiral unit ratio of the obtained copolymer was
smaller than the initial feed ratio of the chiral monomer.
This would be due to the unoptimized polymerization condi-
tions, especially the addition rate of 7. In this study, we did
not further optimize the polymerization conditions, because
the time-conversion profiles mentioned above showed that
the distribution of (S)-5 and 7 units in copolymers 2 listed
in Table 2 were sufficiently random for examination of the
‘‘sergeants and soldiers’’ effect.
units were randomly distributed, the more reactive monomer
7 was added dropwise to the reaction mixture containing
(S)-5 and LiHMDS. When a THF solution of 7 was added
dropwise over 3 h at a constant rate to a THF solution of
(S)-5 ([(S)-5]0/[7]0 ¼ 75/25), 3 mol % of 4, and 1 equiv of
ꢀ
LiHMDS at –10 C, the conversion of the achiral monomer 7
increased at almost the same rate as that of the chiral mono-
mer (S)-5 during the polymerization (Fig. 3). This result indi-
cates that the obtained copolymer 2 had a nearly random
sequence of (S)-5 and 7 units. Furthermore, chain-growth
polymerization nature of this polymerization was suggested
by the low Mw/Mn values (less than 1.10) of the growing
polymers. After the dropwise addition of 7, quenching of the
polymerization and usual work-up afforded a crude product
with Mn and Mw/Mn values of 6900 and 1.10, respectively.
Purification of the crude product by preparative HPLC gave
the copolymer 266/34 of which the chiral/achiral unit ratio
was 66/34. Copolymerization of (S)-5 and 7 with the initial
monomer feed ratios ([(S)-5]0/[7]0) of 50/50 and 25/75
afforded the copolymers 233/67 and 216/84, respectively
Random Copolymerization of Enantiomeric Monomers
Copolymerization of (S)-5 and (R)-5 for the synthesis of 3
(Scheme 4) was carried out using chiral monomer (S)-5 and
racemic monomer rac-5. We did not use (R)-5, because the
synthesis of rac-5 was easier than that of (R)-5. When a 1:1
mixture of (S)-5 and rac-5 ([(S)-5]0/[(R)-5]0) ¼ 75/25) was
ꢀ
added to a THF solution of LiHMDS at –10 C all at once and
FIGURE 3 Time–conversion plots for the copolymerization of
(S)-5 and 7 ([(S)-5]0/[7]0) ¼ 75/25) with dropwise addition of 7.
The copolymerization was carried out by dropwise addition of
FIGURE 2 Time–conversion plots for the copolymerization of
(S)-5 and 7 ([(S)-5]0/[7]0) ¼ 75/25). The copolymerization was
carried out in the presence of 4 (([(S)-5]0 þ [7]0)/[4]0 ¼ 28) and
LiHMDS (0.90 equiv to the monomers) in THF at ꢂ10 ꢀC.
a THF solution of 7 to a THF solution of [(S)-5], 4 (([(S)-5]0
þ
[7]0)/[4]0 ¼ 31) and LiHMDS (1.0 equiv to the monomers) over 3
h at ꢂ10 ꢀC.
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TABLE 2 Copolymerization of (S)-5 and 7 by Dropwise Addition of 7 for the Synthesis of 2
Reaction Conditionsa
Copolymer 2
Feed Ratio Reaction
Chiral/Achiral
Unit Ratioc
b
b
Entry
([(S)-5]0/[7]0)
Time (h)
2
Mn
Mw/Mn
1
2
3
a
75/25
50/50
25/75
3.0
3.0
3.0
266/34
233/67
216/84
7,900
10,600
12,500
1.05
1.15
1.27
66/34
33/67
16/84
Copolymerization of (S)-5 and 7 was carried out by dropwise addition of a THF solution of 7 over 3 h to a
THF solution containing (S)-5, 3 mol % of 4, and 1.0 equivalent of LiHMDS, with stirring, at ꢂ10 ꢀC.
b
Determined by GPC based on polystyrene standards (eluent: THF).
c
Determined by 1H NMR in CDCl3.
SCHEME 4 Synthesis of random copolymer 3.
the copolymerization was carried out at that temperature,
the two monomers were consumed at almost the same rate
(Fig. 4), indicating the formation of random copolymer con-
sisting of (S)- and (R)-monomer units. The Mw/Mn values of
the growing polymers were less than 1.12, suggesting the
chain-growth polymerization nature of this copolymerization.
By changing the feed ratio of (S)-5 and rac-5, we synthesized
copolymer 3 with different (S)/(R) ratios in the same man-
ner (Table 3, entries 1–2). To check whether a combination
of Et3SiN(C8H17)Ph/CsF/18-crown-632 functions as a base,
the copolymerization with [(S)-5]0/[rac-5]0 of 24/76 was
carried out with this base system instead of LiHMDS. The
copolymerization proceeded well to afford 324/76 with Mn
and Mw/Mn values of 3600 and 1.20, respectively (entry 3).
in proportion to the chiral unit ratio of 2 and the excess of
the (S)-unit of 3 [Fig. 6(b,c)]. The linear relationships indi-
cate the absence of ‘‘sergeants and soldiers’’ and ‘‘majority
rules’’ effects, that is, there is almost no cooperativity
between the monomer units along the copolymers 1–3. The
absence of cooperativity might result from the loose winding
of the helical structures of 1–3. Another factor that might
decrease the cooperativity is the location of the chiral center
of the monomer units. The helical structure of N-substituted
poly(p-benzamide) with cis conformation of the amide link-
age and syn arrangement of three consecutive benzene rings
requires the side chain to be located outside the backbone
helix. Therefore, steric interaction between chiral centers
located near each other and between the chiral center and
‘‘Sergeants and Soldiers’’ and ‘‘Majority Rules’’
Experiments
To elucidate the cooperativity between monomer units in the
copolymers 1–3, we measured their CD spectra in solution
and investigated the relationship between the CD spectra
and the monomer composition of the copolymers. The CD
spectra of the copolymers 1 and poly[(S)-5] in chloroform
were similar in shape, and the intensity of CD signal
increased with increase of the chiral unit ratio (Fig. 5). This
result indicates that the CD signal originates from the right-
handed helical structure with three monomer units per turn
as in the case of poly[(S)-5]22 and that the degree of appear-
ance of the right-handed helical structure depended on the
chiral unit ratio in the copolymer. When the intensity of the
CD signal at 254 nm, at which the spectra showed a negative
local maximum, was plotted as a function of the chiral unit
ratio, a linear relationship was obtained [Fig. 6(a)].
FIGURE 4 Time–conversion plots for the copolymerization of
(S)-5 and (R)-5 ([(S)-5]0/[(R)-5]0) ¼ 75/25). The copolymerization
The CD spectra of the copolymers 2 and 3 showed the same
behavior as those of 1: the shapes of the CD spectra were
similar, and the intensities of the CD signal changed linearly
was carried out in the presence of 4 (([(S)-5]0 þ [(R)-5]0)/[4]0
¼
29) and LiHMDS (1.0 equiv to the monomers) in THF at –10 ꢀC.
N-SUBSTITUTED p-BENZAMIDE RANDOM COPOLYMERS, YOKOYAMA ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
TABLE 3 Copolymerization of (S)-5 and rac-5 for the Synthesis of 3
Reaction Conditions
Copolymer 3
Feed Ratio
Reaction
Time (h)
Methoda
3
Mn
Mw/Mn
b
b
Entry
([(S)-5]0/[rac-5]0)
(S)/(R) of 5
1
2
3
a
74/26
50/50
24/76
87/13
75/25
62/38
A
A
B
4.0
3.5
387/13
375/25
324/76
6,500
3,900
3,600
1.08
1.10
1.20
11.5
Method A: the copolymerization was carried out using LiHMDS (1.0 equivalent) as a base in the presence
of 3 mol % of 4 in THF at ꢂ10 ꢀC. Method B: the copolymerization was carried out using a combination of
Et3SiN(C8H17)Ph (0.95 equiv)/CsF (1.0 equiv)/18-crown-6 (2.0 equiv) as a base in the presence of 4 mol % of
4 in THF at room temperature.
b
Determined by GPC based on polystyrene standards (eluent: THF).
helical backbone might be small, and the chiral center might
control the conformation of only one benzanilide unit or less
of the poly(p-benzamide).
Unlike typical dynamic helical polymers, which equilibrate
between right- and left-handed helices, N-substituted poly(p-
benzamide) is a foldamer-based helical polymer, and the
copolymers 1–3 should exist in equilibrium between the hel-
ical conformation and random conformation. Although the
CD spectra of poly[(S)-5] showed higher intensity than those
of the copolymers 1–3, the nonsaturated linear increase of
CD intensity with increasing chiral unit ratio and excess of
enantiomeric monomer unit indicates that not all of the
poly[(S)-5] molecules adopt right-handed helical conforma-
tion. In other words, poly[(S)-5] also exists in equilibrium
between right- and left-handed helical conformations and/or
random conformation. This is also supported by the fact that
the CD intensity of poly[(S)-5] in CHCl3 increased when the
22
ꢀ
measurement temperature was lowered from 15 to 0 C.
CONCLUSIONS
FIGURE 5 CD spectra of the copolymer 1 with various chiral
unit ratios (22, 43, and 73%) and of poly[(S)-5] (chiral unit ratio
¼ 100%) and UV–vis spectrum of poly[(S)-5] in CHCl3 at 24 ꢀC.
Three types of random copolymers with a poly(p-benzamide)
backbone were synthesized in a chain-growth condensation
polymerization manner. The chiral/achiral random copoly-
mer 1 was synthesized by the addition of a mixture of 4,
(S)-5 and 6 to a solution of LiHMDS all at once. The (R)/(S)
FIGURE 6 Plots of CD intensity (254 nm) of (a) 1 and (b) 2 versus chiral unit ratio, and of (c) 3 versus excess of (S)-unit. The CD
spectra of the copolymers were measured in CHCl3 at 24 ꢀC.
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ARTICLE
13 Moore, J. S.; Gorman, C. B.; Grubbs, R. H. J Am Chem Soc
random copolymer 3 could also be synthesized similarly
from (S)-5 and rac-5. On the other hand, the synthesis of the
chiral/achiral random copolymer 2 having a bulky and
branching achiral side chain required dropwise addition of a
THF solution of 7 to a mixture of (S)-5, 4, and LiHMDS. The
CD spectra of the random copolymers 1–3 and the homopol-
ymer poly[(S)-5] in chloroform were similar in shape, and
the intensities changed linearly in proportion to the chiral
unit ratio of 1 and 2 and the excess of the (S) unit in 3, indi-
cating the absence of cooperativity between the monomer
units along these copolymers. To increase the steric interac-
tion between monomer units, further studies on the synthe-
sis of poly(p-benzamide) possessing a bulky chiral side chain
are in progress.
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