Chirality organization of aniline oligomers through hydrogen bonds of amino acid moieties

Article abstract of DOI:10.1021/jo100853b

Aniline oligomers bearing amino acid moieties were designed by the introduction of l/d-Ala-OMe into aniline oligomers to induce chirality organization of the π-conjugated aniline oligomer moieties, wherein the formation of intramolecular hydrogen bonds wa

Full text of DOI:10.1021/jo100853b

pubs.acs.org/joc
control of molecular self-organization is of importance for
Chirality Organization of Aniline Oligomers through
Hydrogen Bonds of Amino Acid Moieties
the development of functional materials.4 The utilization of
amino acid moieties, which possess chiral centers and hydro-
gen-bonding sites, is considered to be a relevant approach to
highly ordered molecular assemblies. In this system, inter/
intramolecular hydrogen bonds play a critical role in enforc-
ing well-defined assembly structures. We herein report the
synthesis and characterization of the chirality-organized
aniline oligomers by introduction of the amino acid moieties.
Two types of aniline tetramers, 1 and 2, bearing alanine
moieties are designed to investigate the chirality-organized
structures (Figure 1). 1 and 2 were synthesized from L/D-
alanine methyl ester hydrochloride salt and the carboxylic
acids which were prepared from the ethyl esters 3 and 4. The
thus-obtained aniline tetramers were fully characterized by
spectral data and elemental analyses.
Satoshi D. Ohmura, Toshiyuki Moriuchi,* and
Toshikazu Hirao*
Department of Applied Chemistry, Graduate School of
Engineering, Osaka University, Yamada-oka, Suita,
Osaka 565-0871, Japan
moriuchi@chem.eng.osaka-u.ac.jp;
hirao@chem.eng.osaka-u.ac.jp
Received May 8, 2010
In the 1H NMR spectra of 1-L in CD2Cl2 (5.0 ꢀ 10-3 M),
the central-amino NHs of the aniline moieties were hardly
perturbed by the addition of an aliquot of DMSO-d6 to
CD2Cl2 (CD2Cl2: 9.26 ppm, CD2Cl2-DMSO-d6 (9:1): 9.28
ppm) although the terminal-amino NHs showed a slight
downfield shift (CD2Cl2: 8.02 ppm, CD2Cl2-DMSO-d6 (9:1):
8.27 ppm). The FT-IR spectrum of 1-L in dichloromethane
(5.0 ꢀ 10-3 M) showed the hydrogen-bonded NHs stretching
bands at 3293 and 3333 cm-1. The central-amino NHs are
indicated to be locked in strong intramolecular hydrogen
bonds and the terminal-amino NHs might participate in
weak intramolecular hydrogen bonds in a solution state.
The 1H NMR spectra of 2-L in CD2Cl2 (5.0 ꢀ 10-3 M) indi-
cate that the central-amino NHs of the aniline moieties were
hardly perturbed by the addition of an aliquot of DMSO-d6
to CD2Cl2 (CD2Cl2: 7.94 ppm, CD2Cl2-DMSO-d6 (9:1): 8.17
ppm), although the terminal-amino NHs were perturbed
decidedly (CD2Cl2: 5.70 ppm, CD2Cl2-DMSO-d6 (9:1):
6.48 ppm). The FT-IR spectrum of 2-L in CH2Cl2 (5.0 ꢀ
10-3 M) showed hydrogen-bonded NH and not hydrogen-
bonded NH stretching bands at 3342 and 3423 cm-1 in a
solution state, respectively. These results indicate that the
central-amino NHs form the intramolecular hydrogen bonds
although the terminal-amino NHs do not participate in
hydrogen bonding.
Aniline oligomers bearing amino acid moieties were de-
signed by the introduction of L/D-Ala-OMe into aniline
oligomers to induce chirality organization of the π-con-
jugated aniline oligomer moieties, wherein the formation
of intramolecular hydrogen bonds was demonstrated to
play an important role to regulate the aniline oligomer
moieties conformationally.
π-Conjugated polymers are of potential for the applica-
tion to electronic materials. One of the most important
π-conjugated polymers, polyaniline, is redox-active and
present in various redox states.1 Recently, there has been
increased interest in chiral induction of polyanilines because
of their use in diverse areas for surface-modified electrodes,
molecular recognition, and chiral separation.2 In previous
papers, the introduction of chiral transition metal complexes
into poly(o-toluidine) has been demonstrated to afford chiral
d,π-conjugated complex systems.3 Bioinspired architectural
The electronic spectrum of 1-L in dichloromethane ex-
hibited a broad absorption at around 450 nm, which is
probably due to a low-energy charge-transfer transition of
the π-conjugation moiety (Figure 2a).3,5 It should be noted
that 1-L exhibits an induced circular dichroism (ICD) at the
absorbance region of the π-conjugated moiety. This result
(1) (a) Pouget, J. P.; Laridjani, M.; Jozefowicz, M. E.; Epstain, A. J.;
Scherr, E. M.; MacDiarmid, A. G. Synth. Met. 1992, 51, 95. (b) Lux, F.
Polymer 1994, 35, 2915. (c) MacDiarmid, A. G. Synth. Met. 1997, 84, 27.
(d) Malinauskas, A. J. Power Sources 2004, 126, 214. (e) Wang, Y.; Zhang, D.
Mater. Sci. Eng., B 2006, 134, 9. (f) Miras, M. C.; Acevedo, D. F.; Monge, N.;
Frontera, E.; Rivarola, C. R.; Barbero, C. A. Open Macromol. J. 2008, 1, 58.
(2) (a) Majidi, M. R.; Kane-Maguire, L. A. P.; Wallace, G. G. Polymer
1994, 35, 3113. (b) Ashraf, S. A.; Kane-Maguire, L. A. P.; Majidi, M.-R.;
Pyne, S. G.; Wallace, G. G. Polymer 1997, 38, 2627. (c) Uemura, S.;
Kusabuka, K.; Nakahira, T.; Kobayashi, N. J. Mater. Chem. 2001, 11,
267. (d) Nagarajan, R.; Liu, W.; Kumar, J.; Tripathy, S. K.; Bruno, F. F.;
Samuelson, L. A. Macromolecules 2001, 34, 3921. (e) Yuan, G.-L.;
Kuramoto, N. Chem. Lett. 2002, 544. (f) Yuan, G.-L.; Kuramoto, N.
Macromolecules 2002, 35, 9773. (g) Li, W.; Wang, H.-L. J. Am. Chem. Soc.
2004, 126, 2278. (h) Zhang, X.; Song, W. Polymer 2007, 48, 5473.
(4) For recent reviews, see: (a) Hill, D. J.; Mio, M. J.; Prince, R. B.;
Hughes, T. S.; Moore, J. S. Chem. Rev. 2001, 101, 3893. (b) Archer, E. A.;
Gong, H.; Krische, M. J. Tetrahedron 2001, 57, 1139. (c) Huc, I. Eur. J. Org.
Chem. 2004, 17. (d) Moriuchi, T.; Hirao, T. Chem. Soc. Rev. 2004, 33, 294.
(e) Sanford, A. R.; Yamato, K.; Yang, X.; Yuan, L.; Han, Y.; Gong, B. Eur.
J. Biochem. 2004, 271, 1416. (f) Goodman, C. M.; Choi, S.; Shandler, S.;
DeGrado, W. F. Nat. Chem. Biol. 2007, 3, 252. (g) Gong, B. Acc. Chem. Res.
2007, 41, 1736. (h) Kim, H.-J.; Lim, Y.-B.; Lee, M. J. Polym. Sci., Part A:
Polym. Chem. 2008, 46, 1925. (i) Yashima, E.; Maeda, K.; Iida, H.; Furusho,
Y.; Nagai, K. Chem. Rev. 2009, 109, 6102. (j) Saraogi, I.; Hamilton, A. D.
Chem. Soc. Rev. 2009, 38, 1726.
(3) (a) Shen, X.; Moriuchi, T.; Hirao, T. Tetrahedron Lett. 2004, 45, 4733.
(b) Moriuchi, T.; Shen, X.; Hirao, T. Tetrahedron 2006, 62, 12237.
(5) Moriuchi, T.; Kikushima-Honda, N.; Ohmura, S. D.; Hirao, T.
Tetrahedron Lett. 2010, 51, 4530.
DOI: 10.1021/jo100853b
r
Published on Web 10/19/2010
J. Org. Chem. 2010, 75, 7909–7912 7909
2010 American Chemical Society

Ohmura et al.
JOCNote
indicates that the chirality induction of a π-conjugated
backbone aniline oligomer is achieved by the chirality organ-
ization based on the intramolecular hydrogen bonding. The
mirror image of the CD signals observed with 1-L was ob-
tained in the CD spectrum of 1-D as shown in Figure 2b,
indicating that a chiral molecular arrangement based on the
regulated structures via intramolecular hydrogen bonding is
formed. ICD and the mirror-imaged CD signals were also
observed in the case of 2.
The CD signals of 1-L were changed at around 360 nm by
the addition of DMSO (Figure 2c). On the contrary, only a
little change of the CD signals was observed in the case of 2-
L. The shape of the CD signal of 1 in CH2Cl2-DMSO (1:1) is
similar to that of 2 in CH2Cl2-DMSO (1:1). From the
above-mentioned results of the 1H NMR and FT-IR experi-
ments, the chirality-organized structure is considered to be
preserved through the intramolecular hydrogen bonding of
the central-amino NHs in CH2Cl2-DMSO (1:1).
Theorientation of thebenzene rings has thedihedral anglesof
149.5(2)° (central) and 125.4(1)° (terminal) as shown in
Figure 3a. A similar structure is considered to be formed
with 1 to permit chirality organization of the aniline oligo-
mers through hydrogen bonding of the amino acid moieties.
The packing structure of the tetraethyl ester 3 exhibited the
ordered-layer structure through π-π stacking (Figure 3b).
Contrary to the molecular structure of 3, a syn-anti-syn-
conformation of the π-conjugated moieties based on intra-
molecular hydrogen bonding was observed in the crystal
structure of the diethyl ester 4 (Figure 4a).This difference
might arise from the existence of the hydrogen bonds. While
all NHs of 3 participated in the intramolecular hydrogen
bonds to regulate the conformation of the π-conjugated
moieties, the terminal moieties of 4 were not regulated be-
cause of the absence of the hydrogen bonds in the terminal-
amino NHs. The formation of the intramolecular hydrogen
bonds was found to play an important role in the structural
regulation of the π-conjugated moieties. The orientation of
the benzene rings of 4 has the dihedral angles of 98.15(4)°
(central) and 62.52(6)° (terminal). Contrary to the packing
structure of 3, the diethyl ester 4 exhibited the sheet-like self-
assembly through the intermolecular hydrogen-bonding net-
works, wherein each molecule is bonded to two neighboring
On the basis of these observations, the structural elucida-
tion of 1 and 2 was investigated by crystal structural analysis
of the ethyl esters 3 and 4. The crystal structure of the tetra-
ethyl ester 3 revealed the formation of the intramolecular
hydrogen bonds between the amino NH and CO, resulting in
an anti-anti-anti-conformation of the π-conjugated moieties.
FIGURE 3. (a) Crystal structure of 3. (b) Portion of a layer contain-
ing the ordered-layer structure through π-π stacking in the crystal
packing of 3.
FIGURE 1. Structures of aniline tetramer derivatives.
FIGURE 2. (a) Absorption spectra of 1-L and 2-L. (b) CD spectra of 1 and 2 in CH2Cl2 (5.0 ꢀ 10-5 M) and (c) 1-L and 2-L in CH2Cl2-DMSO
(1:1) (5.0 ꢀ 10-5 M) at 25 °C under nitrogen atmosphere.
7910 J. Org. Chem. Vol. 75, No. 22, 2010

Ohmura et al.
JOCNote
Experimental Section
Synthesis of Ethyl 2-(4-Aminophenylamino)benzoate. To a
mixture of cesium carbonate (3.10 g, 9.5 mmol), palladium(II)
acetate (89.8 mg, 0.40 mmol), (()-BINAP (218 mg, 0.35 mmol),
ethyl 2-bromobenzoate (454 mg, 2.0 mmol), and p-phenylene-
diamine (865 mg, 8.0 mmol) was added anhydrous toluene
(40 mL). The mixture was stirred at 100 °C for 48 h under argon
atmosphere. After cooling to ambient temperature, dichloro-
methane (30 mL) was added to the brown suspension and
filtered. After evaporation of the solvent, a residue was purified
by silica-gel column chromatography (from hexane to hexane/
EtOAc = 4:1) to give the expected compound (62.0 mg, 0.24
mmol) as a brown-yellow solid, Rf = 0.64 (hexane/EtOAc =
5:2): yield 66%; mp 72-73 °C (uncorrected); IR (KBr) 3289, 3253,
3033, 2992, 2975, 1681, 1583, 1522, 1478, 1449 cm-1; 1H NMR
(400 MHz, CD2Cl2, 1.0 ꢀ 10-2 M) δ 9.17 (s, 1H), 7.93 (dd, 1H,
J = 7.8, 1.8 Hz), 7.23 (dt, 1H, J = 7.8, 1.8 Hz), 7.02 (dd, 2H, J =
6.4, 1.8 Hz), 6.89 (dd, 1H, J = 7.8, 0.9 Hz), 6.69 (dd, 2H, J = 6.4,
1.8 Hz), 6.62 (dt, 1H, J = 7.8, 0.9 Hz), 4.33 (q, 2H, J = 7.3 Hz),
3.69 (s, 2H), 1.38 (t, 3H, J = 7.3 Hz); 13C NMR (100 MHz,
CD2Cl2, 1.0 ꢀ 10-2 M) 168.9, 150.5, 144.5, 134.3, 131.8, 131.6,
126.7, 116.1, 116.0, 113.6, 111.2, 60.9, 14.6 ppm; HRMS (FAB)
m/z: [M]þ 256.1220, C15H16N2O2 (calcd 256.1212); Anal. Calcd
for C15H16N2O2: C, 71.27; H, 5.98; N, 6.93. Found: C, 71.15; H,
5.91; N, 6.87.
General Procedure for Synthesis of Tetraalanyl Derivative 1. A
mixture of 3 (73.0 mg 0.10 mmol) and sodium hydroxide (∼180
mg) in tetrahydrofuran (10 mL) was refluxed for 27 h. After
the reaction was completed, the solvent was evaporated, and the
residue was dried in vacuo. Water (15 mL) was added to the
residue, and the solution was acidified with 1 N HCl aqueous
solution. The dark-brown precipitate was isolated by filtration,
washed with water, and dried in vacuo. Anhydrous dichloro-
methane (40 mL) was added to a mixture of the thus-obtained
dark-brown solid, 1-hydroxybenzotriazole (108 mg, 0.80 mmol),
L/D-alanine methyl ester hydrochloride (112 mg, 0.8 mmol),
and triethylamine (0.5 mL). The mixture was stirred at 0 °C,
and a solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodi-
imide hydrochloride (154 mg, 0.80 mmol) in anhydrous dichloro-
methane (40 mL) was dropwise added to the mixture over 1 h.
Then, the mixture was stirred at ambient temperature for 25 h.
The resulting mixture was diluted with dichloromethane (10 mL),
washed with saturated NaHCO3 aqueous solution (30 mL ꢀ 2),
water (30 mL) and saturated NaCl aqueous solution (30 mL).
After separating and discarding the water phase, the organic
phase was dried on Na2SO4. After evaporation of the solvent, a
mixture was purified by silica-gel column chromatography (from
CH2Cl2 to CH2Cl2/EtOAc = 3:1) to give 1 as a yellow solid (1-L:
162 mg; 1-D: 87.6 mg), Rf = 0.25 (CH2Cl2/EtOAc = 3:1); 1-L:
yield 61%; mp 167-168 °C (uncorrected); IR (CH2Cl2, 5.0 ꢀ
10-3 M) 3316, 1696, 1578, 1522, 1443, 1414, 1313, 1237, 1211
cm-1; 1H NMR (400 MHz, CD2Cl2, 5.0 ꢀ 10-3 M) δ 9.26 (s, 2H),
8.02(s, 2H), 7.53(s, 2H), 7.50 (d, 2H, J =7.9 Hz), 7.27 (t, 2H, J =
7.9 Hz), 7.19(d, 2H, 7.9 Hz), 7.15 (d, 4H, J = 6.7 Hz), 7.06 (d, 4H,
J = 6.7 Hz), 7.00 (d, 2H, J = 7.3 Hz), 6.74 (t, 2H, J = 7.9 Hz),
6.69(d, 2H, J = 6.9 Hz), 4.71 (quint, 2H, J =7.3 Hz), 4.64 (quint,
2H, J= 7.3 Hz), 3.77 (s, 6H), 3.72 (s, 6H), 1.50 (d, 6H, J=7.3 Hz),
1.42 (d, 6H, J = 7.3 Hz); 13C NMR (100 MHz, CD2Cl2,
5.0 ꢀ 10-3 M) 173.9, 173.4, 169.3, 167.6, 147.3, 139.0, 137.3,
136.0, 132.9, 128.2, 125.0, 123.9, 120.7, 118.4, 117.5, 116.8,
115.0, 52.9, 52.8, 48.9, 48.8, 18.6, 18.4 ppm; HRMS (FAB)
m/z: [M]þ 958.3864, C50H54N8O12 (calcd 958.3861) Anal.
Calcd for C50H54N8O12: C, 62.62; H, 5.68; N, 11.68. Found:
C, 62.48; H, 5.41; N, 11.54: 1-D: yield 33%; mp 167-168 °C
(uncorrected); IR (CH2Cl2, 5.0 ꢀ 10-3 M) 3316, 1696, 1578,
1522, 1443, 1414, 1313, 1237, 1211 cm-1; 1H NMR (400 MHz,
CD2Cl2, 5.0 ꢀ 10-3 M) δ 9.26 (s, 2H), 8.02 (s, 2H), 7.53 (s, 2H),
FIGURE 4. (a) Crystal structure of 4. (b) Portion of a layer contain-
ing the sheet-like self-assembly through intermolecular hydrogen-
bonding networks and (c) the π-π stacking between the hydrogen-
bonded sheets in the crystal packing of 4.
molecules by an 18-membered hydrogen-bonded ring
˚
(O(1) N(2), 2.19 A; O(1*) N(2*), 2.19 A) (Figure 4b).
˚
3 3 3
3 3 3
Furthermore, each hydrogen-bonded sheet was connected
through the π-π stacking (Figure 4c).
The redox properties of 1-4 were disclosed by cyclic
voltammetry (see Figure S2, Supporting Information). Tetra-
alanyl oligomer 1 in dichloromethane showed three consecu-
tive redox waves (E0 = 0.24, 0.44, and 0.76 V vs Fc/Fcþ). The
waves at 0.24 and 0.44 V were assigned to consecutive one-
electron oxidation of the phenylenediamine moieties to give
the corresponding oxidized species. The most positive anodic
peak with twice the height (E03 =0.76 V) is attributable to
successive one-electron oxidation processes of the two termi-
nal phenylenediamine moieties. The three successive redox
waves (E0 = -0.06, 0.09, and 0.48 V vs Fc/Fcþ) were also
observed in the cyclic voltammogram of the oligomer 2. All of
the redox waves were more cathodic than those of 1. The shift
is probably due to the absence of the electron-withdrawing
substituent at the terminal benzene rings.
In conclusion, the formation of the hydrogen bonds was
found to play an important role in the conformational
regulation of the oligoanilines by the introduction of L/D-
alanine moieties. The hydrogen-bond regulated chirality
organization of the π-conjugated moieties has been achieved.
Studies on the application of the chirality-organized aniline
oligomers or polymers for molecular recognition and molec-
ular dynamics are now in progress.
J. Org. Chem. Vol. 75, No. 22, 2010 7911

Ohmura et al.
JOCNote
7.50 (d, 2H, J = 7.9 Hz), 7.27 (t, 2H, J = 7.9 Hz), 7.19 (d, 2H,
7.9 Hz), 7.15 (d, 4H, J = 6.7 Hz), 7.06 (d, 4H, J = 6.7 Hz), 7.00
(d, 2H, J = 7.3 Hz), 6.74 (t, 2H, J = 7.9 Hz), 6.69 (d, 2H, J =
6.9 Hz), 4.71 (quint, 2H, J = 7.3 Hz), 4.64 (quint, 2H, J = 7.3
Hz), 3.77 (s, 6H), 3.72 (s, 6H), 1.50 (d, 6H, J = 7.3 Hz), 1.42 (d,
6H, J = 7.3 Hz); 13C NMR (100 MHz, CD2Cl2, 5.0 ꢀ 10-3 M)
173.9, 173.4, 169.3, 167.6, 147.3, 139.0, 137.3, 136.0, 132.9,
128.2, 125.0, 123.9, 120.7, 118.4, 117.5, 116.8, 115.0, 52.9,
52.8, 48.9, 48.8, 18.6, 18.4 ppm; HRMS (FAB) m/z: [M]þ
958.3858, C50H54N8O12 (calcd 958.3861).
Synthesis of 3. A solution of p-toluenesulfonate monohydrate
(28.5 mg, 0.15 mmol) in ethanol (15 mL) was added to a mixture
of diethyl 2,5-dioxocyclohexane-1,4-dicarboxylate (51.3 mg,
0.20 mmol) and ethyl 2-(4-aminophenylamino)benzoate (154
mg, 0.60 mmol). The mixture was stirred at reflux for 12 h under
argon atmosphere. Once cooling to ambient temperature, the
mixture was stirred at reflux for 32 h under oxygen atmosphere.
After cooling to ambient temperature, the precipitate was iso-
lated by filtration, washed with ethanol, and dried in vacuo.
Aniline tetramer 3 (157 mg) was obtained as a red crystal by
recrystallization from dichloromethane: yield 98%; mp 195-
197 °C (uncorrected); IR (CH2Cl2, 5.0 ꢀ 10-3 M) 3412, 3337,
3268, 3181, 3161, 1684, 1581, 1515, 1382, 1370, 1314 cm-1; 1H
NMR (400 MHz, CD2Cl2, 5.0 ꢀ 10-3 M) δ 9.38 (s, 2H), 7.99 (s,
2H), 7.97 (d, 2H, J = 8.0 Hz), 7.30 (t, 2H, J = 8.0 Hz),
7.23-7.19 (m, 10H), 7.13 (d, 2H, J = 8.0 Hz), 6.70 (t, 2H,
J = 8.0 Hz), 4.35 (q, 4H, J = 7.3 Hz), 4.33 (q, 4H, J = 7.3 Hz),
1.40 (t, 6H, J = 7.3 Hz), 1.34 (t, 6H, J = 7.3 Hz); 13C NMR
(100 MHz, CD2Cl2, 5.0 ꢀ 10-3 M) 167.7, 166.7, 148.1, 133.2,
130.8, 123.9, 123.8, 120.9, 120.3, 118.3, 117.4, 115.8, 115.7,
112.8, 110.9, 60.5, 59.9, 13.4, 13.2 ppm; HRMS (FAB) m/z:
[M]þ 730.2989, C42H42N4O8 (calcd 730.3003).
Synthesis of 4. A mixture of diethyl 2,5-dioxocyclohexane-
1,4-dicarboxylate (256 mg, 1.0 mmol) and p-aminodiphenyl-
amine (369 mg, 2.0 mmol) in acetic acid (15 mL) was stirred at
100 °C for 18 h. After cooling to ambient temperature, the
precipitate was isolated by filtration, washed with ethanol, and
dried in vacuo. Chloroform (15 mL) was added to the pink solid,
which was refluxed for 10 h under oxygen atmosphere. After
evaporation of the solvent, 4 (498 mg) was obtained as a red crys-
tal by recrystallization from toluene: yield 85%; mp 211-213 °C
(uncorrected); IR(CH2Cl2, 5.0ꢀ 10-3 M) 3416, 3361, 2926, 1686,
1599, 1513, 1103, 1020 cm-1; 1H NMR (400 MHz, CD2Cl2, 5.0 ꢀ
10-3 M) δ 8.63 (s, 2H), 7.89 (s, 2H), 7.24 (t, 4H, J = 7.8 Hz), 7.14
(d, 4H, J = 8.7 Hz), 7.10 (d, 4H, J = 8.7 Hz), 7.01 (d, 2H,
J = 7.8 Hz), 6.86 (t, 2H, J = 7.8 Hz), 5.73 (s, 2H), 4.31 (q, 4H,
J = 7.3 Hz), 1.33 (t, 6H, J = 7.3 Hz); 13C NMR (100 MHz,
CD2Cl2, 5.0 ꢀ 10-3 M) 167.9, 144.8, 138.9, 138.2, 136.7, 129.7,
122.4, 120.8, 120.4, 119.0, 118.1, 116.7, 61.6, 14.4 ppm; HRMS
(FAB) m/z: [M]þ 586.2582, C36H34N4O4 (calcd 586.2580).
General Procedure for Synthesis of Dialanyl Derivative 2. A
mixture of 4 (58.6 mg, 0.10 mmol) and sodium hydroxide
(∼100 mg) in tetrahydrofuran (10 mL) was refluxed for 20 h.
After the reaction was completed, the solvent was evaporated,
and the residue was dried in vacuo. Water (15 mL) was added to
the residue, and the solution was acidified with 1 N HCl aqueous
solution. The dark-brown precipitate was isolated by filtration,
washed with water, and dried in vacuo. Anhydrous dichloro-
methane (40 mL) was added to a mixture of the thus-obtained
black solid, 1-hydroxybenzotriazole (27.0 mg, 0.20 mmol),
L/D-alanine methyl ester hydrochloride (27.9 mg, 0.20 mmol),
and triethylamine (0.5 mL). The mixture was stirred at 0 °C,
and a solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodi-
imide hydrochloride(38.3mg, 0.20 mmol) inanhydrous dichloro-
methane (40 mL) was dropwise added to the mixture over 1 h.
Then, the mixture was stirred at ambient temperature for 45 h.
The resulting mixture was diluted with dichloromethane (10 mL),
washed with saturated NaHCO3 aqueous solution (30 mL ꢀ 2),
water (30 mL), and saturated NaCl aqueous solution (30 mL).
After separating and discarding the water phase, the organic
phase was dried on Na2SO4. After evaporation of the solvent, a
mixture was purified by silica-gel column chromatography (from
CH2Cl2 to CH2Cl2/MeOH = 10:1) to give 2 as a yellow solid
(2-L: 29.2 mg; 2-D: 18.9 mg), Rf = 0.63 (CH2Cl2/MeOH = 10:1);
2-L: yield 42%; mp 178-180 °C (uncorrected); IR(CH2Cl2, 5.0 ꢀ
10-3 M) 3424, 3342, 2848, 1738, 1651, 1594, 1508, 1211, 1162,
1063 cm-1; 1H NMR (400 MHz, CD2Cl2, 5.0 ꢀ 10-3 M) δ 7.94 (s,
2H), 7.48 (s, 2H), 7.22 (t, 4H, J = 7.3 Hz), 7.08 (d, 4H, J = 9.2
Hz), 7.03 (d, 4H, J = 9.2 Hz), 6.99 (d, 4H, J = 7.3 Hz), 6.85 (t,
4H, J = 7.3 Hz), 5.70 (s, 2H), 4.64 (quint, 2H, J = 7.3 Hz), 3.71 (s,
6H), 1.41 (d, 6H, J = 7.3 Hz); 13C NMR (100 MHz, CD2Cl2,
5.0 ꢀ 10-3 M) 173.6, 167.6, 144.8, 137.9, 137.7, 137.6, 129.7,
124.7, 121.2, 121.0, 120.3, 118.2, 116.6, 52.9, 48.9, 18.4 ppm; HRMS
(FAB) m/z: [M]þ 700.2998, C40H40N6O6 (calcd 700.3009); 2-D:
yield 27%; mp 178-180 °C (uncorrected); IR (CH2Cl2, 5.0 ꢀ
10-3 M) 3424, 3342, 2848, 1738, 1651, 1594, 1508, 1211, 1162,
1063 cm-1; 1H NMR (400 MHz, CD2Cl2, 5.0 ꢀ 10-3 M) δ 7.94 (s,
2H), 7.48 (s, 2H), 7.22 (t, 4H, J = 7.3 Hz), 7.08 (d, 4H, J = 9.2
Hz), 7.03 (d, 4H, J = 9.2 Hz), 6.99 (d, 4H, J = 7.3 Hz), 6.85 (t,
4H, J = 7.3 Hz), 5.70 (s, 2H), 4.64 (quint, 2H, J = 7.3 Hz), 3.71 (s,
6H), 1.41 (d, 6H, J = 7.3 Hz); 13C NMR (100 MHz, CD2Cl2,
5.0 ꢀ 10-3 M) 173.6, 167.6, 144.8, 137.9, 137.7, 137.6, 129.7,
124.7, 121.2, 121.0, 120.3, 118.2, 116.6, 52.9, 48.9, 18.4 ppm;
HRMS (FAB) m/z: [M]þ 700.3022, C40H40N6O6 (calcd 700.3009).
Acknowledgment. One of the authors, S.D.O., expresses
special thanks for the Global COE (center of excellence)
Program “Global Education and Research Center for Bio-
Environmental Chemistry” of Osaka University. Thanks are
due to the Analytical Center, Graduate School of Engineer-
ing, Osaka University, for the use of the NMR and MS
instruments.
Supporting Information Available: Experimental details,
spectroscopic data, and X-ray crystallographic data. This mate-
rial is available free of charge via the Internet at http://
pubs.acs.org.
7912 J. Org. Chem. Vol. 75, No. 22, 2010