Facile preparation of O-substituted acyclic phenol-formaldehyde oligomers

Article abstract of DOI:10.1081/SCC-120015403

Acyclic p-cresol-formaldehyde oligomers (dimer, trimer, and tetramer) having ester, carboxylic acid, amide groups on the phenolic OH groups were prepared in good yields.

Full text of DOI:10.1081/SCC-120015403

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FACILE PREPARATION OF O-SUBSTITUTED ACYCLIC
PHENOL–FORMALDEHYDE OLIGOMERS
Kazuaki Ito a , Toshiro Takasawa a & Yoshihiro Ohba a
a Department of Chemistry and Chemical Engineering , Faculty of Engineering , Yamagata
University , Yonezawa, 992-8510, Japan
Published online: 23 Aug 2006.
To cite this article: Kazuaki Ito , Toshiro Takasawa & Yoshihiro Ohba (2002) FACILE PREPARATION OF O-SUBSTITUTED ACYCLIC
PHENOL–FORMALDEHYDE OLIGOMERS, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:24, 3839-3849, DOI: 10.1081/SCC-120015403
To link to this article: http://dx.doi.org/10.1081/SCC-120015403
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 24, pp. 3839–3849, 2002
FACILE PREPARATION OF
O-SUBSTITUTED ACYCLIC
PHENOL–FORMALDEHYDE OLIGOMERS
*
Kazuaki Ito, Toshiro Takasawa, and Yoshihiro Ohba
Department of Chemistry and Chemical Engineering,
Faculty of Engineering, Yamagata University,
Yonezawa, 992-8510, Japan
ABSTRACT
Acyclic p-cresol-formaldehyde oligomers (dimer, trimer, and
tetramer) having ester, carboxylic acid, amide groups on the
phenolic OH groups were prepared in good yields.
Key Words: Acyclic phenol-formaldehyde oligomer; Calix-
arene; Molecular recognition
Calixarenes are cyclic phenol–formaldehyde condensation products,
which are extensively investigated as host molecules and enzyme mimics.[1]
The corresponding acyclic oligomers have also been found to form stable
complexes with organic molecules, although only a few examples are avail-
able.[2] Recently, we have reported that acyclic phenol–formaldehyde
oligomers with methylene bridges ortho to the phenolic OH group and
their sulfur-bridged and carbonyl-bridged analogs.[3] The inclusion behavior
*Corresponding author. E-mail: itokazu@yz.yamagata-u.ac.jp
3839
DOI: 10.1081/SCC-120015403
Copyright & 2002 by Marcel Dekker, Inc.
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3840
ITO, TAKASAWA, AND OHBA
was remarkably influenced by the bridge moieties and the number of the
phenol units. As an extension of our studies, we synthesized O-substituted
acyclic phenol–formaldehyde oligomers by replacing the phenolic hydrogens
with functional groups such as ester, carboxylic acid, and amide. It is
known that calixarene derivatives having such functional groups serve as
host molecules toward anions, cations, and neutral molecules.[4–6] Here the
results will be reported.
Acyclic p-cresol-formaldehyde oligomers (1) were synthesized by the
stepwise method based on repeated hydroxymethylation–arylation reaction
sequences.[3a] 1 were treated with 2-bromoethyl acetate and NaH in
N,N-dimethylformamide at 80ꢀC to generate the ethyl ester derivatives (2)
in 36–83% yields. Hydrolysis of 2 was carried out by the use of 10% tetra-
methylammonium hydroxide aqueous solution to afford the corresponding
carboxylic acids (3) in 70–83% yields.[5] We examined the synthesis of amide
derivative (6) by the reaction of an amine with the acid chloride (4), which
was prepared by the chlorination of 3 by using thionyl chloride.[6] Reactions
of monomer (4a) or dimer (4b) with L-phenylalanine methyl ester as an
amine gave the required amide derivatives (6a and 6b) in 30 and 80%
yields, respectively. However, the similar reactions using trimer (4c) and
tetramer (4d) gave complex materials due to the instability of 4c and 4d.
Therefore, we prepared the pentafluorophenyl ester (5c and 5d) in 86 and
66% yields, respectively, employing a dicyclohexylcarbodiimide (DCC)
mediated esterifications of 3c and 3d with pentafluorophenol.[7] The reac-
tions of 5c and 5d with L-phenylalanine methyl ester gave the corresponding
amides (6c and 6d) in 52 and 67% yields, respectively.
The structures of the products (2, 3, 4, 5, and 6) were established on the
1
basis of their spectral data and elemental analysis. Their H and 13C NMR
spectral data are compatible with the deduced structures as shown in
Schs. 1 and 2. In IR spectra, the characteristic absorptions of carbonyl
stretching bands of the products (2: ca. 1758 cmꢁ1 for ester group, 3:
ca.1730 cmꢁ1 for carboxylic acid group, 4: ca. 1800 cmꢁ1 for acid chloride
group, 5: ca.1800 cmꢁ1 for ester group, 6: ca. 1750 cmꢁ1 for ester group and
ca. 1670 cmꢁ1 for amide group) were observed. The Fab-mass spectra were
shown at molecular ion peaks (MþH)þ corresponding to the products.
Interestingly, trimer (2c and 3c) and tetramer (2d and 3d) bearing ethyl
ester or carboxylic acid groups on the phenolic OH moieties also gave
(MþNa)þ peaks clearly. This result suggests that these acyclic oligomers
can serve as an ionophore for alkaline metal cations.
In order to elucidate the sodium cation affinity of 2, we measured
13C NMR spectra of 2 (50 mM) in the presence of sodium picrate (50 mM)
in CDCl3 : CD3OD, 1 : 1 solution at 20ꢀC. The large downfield shift was
observed for the carbonyl carbon atom of 2c (Áꢀ co ¼ þ0.31, þ0.14 ppm)

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PHENOL–FORMALDEHYDE OLIGOMERS
3841
Scheme 1.
Scheme 2.

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3842
ITO, TAKASAWA, AND OHBA
and 2d (Áꢀ co ¼ þ0.35, þ0.12 ppm) in the presence of sodium picrate. It can
be rationalized by the C¼Oꢂ ꢂ ꢂNaþ interaction. In contrast, the chemical
shifts of 2a (Áꢀ co ¼ þ0.05 ppm) and 2b (Áꢀ co ¼ þ0.08 ppm) scarcely
changed. These results suggest that the phenol–formaldehyde trimer and
tetramer skeleton play an important role to bind sodium cation.
In summary, we have achieved the preparation of acyclic phenol–
formaldehyde oligomers bearing ester, carboxylic acid, and amide groups
on the hydroxyl groups. The study of the molecular recognition using 2, 3,
and 6 is now in progress.
EXPERIMENTAL
Melting points were measured by Yanagimoto micro melting point
apparatus and were not corrected. 1H and 13C NMR spectra were measured
by Varian INIOVA 500 spectrophotometers (500 MHz for 1H, 125 MHz for
13C). Fab-mass spectra were collected by JEOL JMS AX-505HA spectro-
meter using m-nitrobenzyl alcohol as a matrix. IR spectra were recorded on
FORIBA FT-720 spectrophotometer. All chemicals were reagent grade and
were used without further purification. Compounds (1b–1d) were prepared
by methods already reported in the literature.[3a]
General Procedure for the Preparation of 2
To a solution of 1 (10 mmol) in 90 mL of DMF was added NaH
(17 mmol for 1a, 34 mmol for 1b, 51 mmol for 1c, 68 mmol for 1d).
Subsequently, 2-bromoethyl acetate (13 mmol for 1a, 26 mmol for 1b,
39 mmol for 1c, 52 mmol for 1d) was added and the mixture was heated
at 80ꢀC for 2 h. The reaction mixture was cooled and treated with a second
portion of NaH. 2-Bromoethyl acetate was then added. The reaction mix-
ture was heated again at 80ꢀC for a further 2 h. This operation was repeated
untile no starting materials, followed by 1H NMR spectra. Removal of
DMF under reduced pressure gave oily residue, which was dissolved with
chloroform. The solution was washed with water and then the organic layer
was dried over anhydrous sodium sulfate. Removal of chloroform gave oily
residue, which was subjected to column chromatography on silica gel using
hexane : ethyl acetate 1 : 4 as an eluent to give 2 as a pure form.
2a: The yield is 83%. Oil. IR (CDCl3) 1758 (ꢁCO) cmꢁ1. Fab-mass m/z
195 (MþH)þ. 1H NMR (CDCl3) ꢀ 1.30 (t, J ¼ 7.0 Hz, –OCH2CH3, 3H), 2.29
(s, Ar-CH3, 3H), 4.27 (q, J ¼ 7.0 Hz, –OCH2CH3, 2H), 4.59 (s, –OCH2CO–,
2H), 6.81 (m, Ar-H ꢃ 2, 2H), 7.09 (m, Ar-H ꢃ 2, 2H). 13C NMR (CDCl3) ꢀ

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PHENOL–FORMALDEHYDE OLIGOMERS
3843
14.2, 20.5, 61.3, 65.6, 114.5, 130.0, 131.0, 155.7, 169.1. Elemental Analysis
Calcd for C11H14O3ꢂ0.25 (H2O): C, 66.48; H, 7.35. Found: C, 66.16; H, 7.60.
2b: The yield is 56%. M.p. 87–92ꢀC. IR (CDCl3) 1758 (ꢁCO) cmꢁ1
.
Fab-mass m/z 401 (MþH)þ. 1H NMR (CDCl3) ꢀ 1.29 (t, J ¼ 7.0 Hz,
–OCH2CH3 ꢃ 2, 6H), 2.22 (s, Ar-CH3 ꢃ 2, 6H), 4.05 (s, ArCH2Ar, 2H),
4.25 (q, J ¼ 7.0 Hz, –OCH2CH3 ꢃ 2, 4H), 4.58 (s, –OCH2CO– ꢃ 2, 4H),
6.65 (d, J ¼ 8.0 Hz, Ar-H ꢃ 2, 2H), 6.93 (dd, J ¼ 1.5, 8.0 Hz, Ar-H ꢃ 2,
2H), 7.02 (d, J ¼ 1.5 Hz, Ar-H ꢃ 2, 2H). 13C NMR (CDCl3) ꢀ 14.2, 20.6,
29.7, 61.1, 66.2, 111.6, 127.3, 129.7, 130.8, 131.8, 153.9, 169.3. Elemental
Analysis Calcd for C23H28O6: C, 68.98; H, 7.05. Found: C, 69.17; H, 7.36.
2c: The yield is 36%. Oil. IR (CDCl3) 1758 (ꢁCO) cmꢁ1. Fab-mass m/z
607 (MþH)þ, 629 (MþNa)þ. 1H NMR (CDCl3) ꢀ 1.28 (t, J ¼ 7.0 Hz,
–OCH2CH3 ꢃ 3, 9H), 2.16 (s, Ar-CH3, 3H), 2.23 (s, Ar-CH3 ꢃ 2, 6H),
4.06 (s, ArCH2Ar ꢃ 2, 4H), 4.25 (q, J ¼ 7.0 Hz, –OCH2CH3 ꢃ 3, 6H), 4.37
(s, –OCH2CO–, 2H), 4.59 (s, –OCH2CO– ꢃ 2, 4H), 6.66 (d, J ¼ 8.0 Hz,
Ar-H ꢃ 2, 2H), 6.76 (s, Ar-H ꢃ 2, 2H), 6.91 (d, J ¼ 2.5 Hz, Ar-H ꢃ 2, 2H),
6.95 (dd, J ¼ 2.5, 8.0 Hz, Ar-H ꢃ 2, 2H). 13C NMR (CDCl3) ꢀ 14.1, 20.5,
20.9, 29.5, 60.9, 61.0, 66.1, 70.2, 111.7, 127.5, 129.5, 129.7, 130.9, 131.6,
133.2, 133.7, 152.8, 153.9, 169.1, 169.6. Elemental Analysis Calcd for
C35H42O9ꢂ 1.4(H2O) C, 66.52; H, 7.15. Found: C, 66.74; H, 7.15.
2d: The yield is 50%. Oil. IR (CDCl3) 1758 (ꢁCO) cmꢁ1. Fab-mass m/z
813 (MþNa)þ, 835 (MþNa)þ. 1H NMR (CDCl3) ꢀ 1.27 (t, J ¼ 7.0 Hz,
–OCH2CH3 ꢃ 2, 6H), 1.28 (t, J ¼ 7.0 Hz, –OCH2CH3 ꢃ 2, 6H), 2.15 (s,
Ar-CH3 ꢃ 2, 6H), 2.23 (s, Ar-CH3 ꢃ 2, 6H), 4.05 (s, ArCH2Ar ꢃ 2, 4H),
4.07 (s, ArCH2, 2H), 4.21 (q, J ¼ 7.0 Hz, –OCH2CH3 ꢃ 2, 4H), 4.24 (q,
J ¼ 7.0 Hz, –OCH2CH3 ꢃ 2, 4H), 4.35 (s, –OCH2CO– ꢃ 2, 4H), 4.59 (s,
–OCH2CO– ꢃ 2, 4H), 6.65 (d, J ¼ 8.5 Hz, Ar-H ꢃ 2, 2H), 6.68 (d, J ¼ 2.5 Hz,
Ar-H ꢃ 2, 2H), 6.77 (d, J ¼ 1.5 Hz, Ar-H ꢃ 2, 2H), 6.90 (d, J ¼ 1.5 Hz,
Ar-H ꢃ 2, 2H), 6.95 (dd, J ¼ 2.5, 8.5 Hz, Ar-H ꢃ 2, 2H). 13C NMR
(CDCl3) ꢀ 14.1, 14.2, 20.6, 20.9, 29.5, 61.0, 61.1, 66.0, 70.1, 111.5, 127.5,
129.4, 129.5, 129.7, 130.9, 131.6, 133.2, 133.3, 133.9, 152.8, 153.8, 169.1,
169.2. Elemental Analysis Calcd for C47H56O12ꢂ2.7(H2O), C, 65.52; H,
7.18. Found: C, 65.43; H, 6.95.
General Procedure for the Preparation of 3
A solution of 2 (10 mmol) in THF (125 mL for 2a, 250 mL of 2b, 375 mL
for 2c, 500 mL for 2d) was added to 10% aqueous tetramethylammonium
hydroxide (125 mL for 2a, 250 mL of 2b, 375 mL for 2c, 500 mL for 2d).
The mixture was refluxed for 24 h. After cooling to room temperature, the
reaction mixture was acidified with 35% HCl aqueous solution and stirred for

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3844
ITO, TAKASAWA, AND OHBA
12 h. The resulting white precipitate was collected by filtration and washed
with water. The precipitate was dried under reduced pressure.
3a: The yield is 70%. M.p. 137–140ꢀC. IR (CDCl3) 3430 (ꢁOH), 1733
1
(ꢁCO), 1702 (ꢁCO) cmꢁ1. Fab-mass m/z 166 (MþH)þ. H NMR (CDCl3) ꢀ.
2.30 (s, Ar-CH3, 3H), 4.66 (s, –OCH2CO–, 2H), 6.83 (m, Ar-H ꢃ 2, 2H),
7.11 (m, Ar-H ꢃ 2, 2H), 7.80 (bs, OH, 1H). 13C NMR (DMSO-d6) ꢀ 20.5,
65.0, 114.5, 130.1, 131.4, 155.2, 174.2. Elemental Analysis Calcd for
C9H10O3: C, 65.05; H, 6.07. Found: C, 65.20; H, 6.40.
3b: The yield is 85%. M.p. 248–253ꢀC. IR (CDCl3) 3403 (ꢁOH), 1737
(ꢁCO) cmꢁ1. Fab-mass m/z 345 (MþH)þ, 367 (MþNa)þ. 1H NMR (DMSO-
d6) ꢀ 2.14 (s, Ar-CH3 ꢃ 2, 6H), 3.87 (s, ArCH2Ar, 2H), 4.63 (s,
–OCH2CO– ꢃ 2, 4H), 6.73 (d, J ¼ 8.0 Hz, Ar-H ꢃ 2, 2H), 6.91 (dd, J ¼
1.5, 8.0 Hz, Ar-H ꢃ 2, 2H), 6.96 (d, J ¼ 1.5 Hz, Ar-H ꢃ 2, 2H). 13C NMR
(DMSO-d6) ꢀ 20.4, 29.2, 65.2, 111.6, 127.5, 128.8, 129.6, 131.3, 153.8, 170.7.
Elemental Analysis Calcd for C19H20O6: C, 66.27; H, 5.85. Found: C, 66.18;
H, 6.03.
3c: The yield is 73%. M.p. 243–245ꢀC. IR (CDCl3) 3437 (ꢁOH), 1726
(ꢁCO) cmꢁ1. Fab-mass m/z 523 (MþH)þ, 545 (MþNa)þ. 1H NMR (DMSO-
d6) ꢀ 2.06 (s, Ar-CH3, 3H), 2.17 (s, Ar-CH3 ꢃ 2, 6H), 3.91 (s, ArCH2Ar ꢃ 2,
4H), 4.33 (s, –OCH2CO–, 2H), 4.64 (s, –OCH2CO– ꢃ 2, 4H), 6.74 (s,
Ar-H ꢃ 2, 2H), 6.76 (d, J ¼ 8.0 Hz, Ar-H ꢃ 2, 2H), 6.88 (d, J ¼ 1.5 Hz,
Ar-H ꢃ 2, 2H), 6.96 (dd, J ¼ 1.5, 8.0 Hz, Ar-H ꢃ 2, 2H). 13C NMR
(DMSO-d6) ꢀ 20.3, 20.6, 29.1, 65.0, 69.8, 111.7, 127.6, 128.7, 129.1, 129.5,
131.2, 132.9, 133.2, 152.5, 153.7, 170.3, 170.5. Elemental Analysis Calcd for
C29H30O9: C, 66.66; H, 5.79. Found: C, 66.67; H, 6.03.
3d: The yield is 70 %. M.p. 237–240ꢀC. IR (CDCl3) 3448 (ꢁOH), 1728
(ꢁCO) cmꢁ1. Fab-mass m/z 701 (MþH)þ, 723 (MþNa)þ. 1H NMR (DMSO-
d6) ꢀ 2.07 (s, Ar-CH3 ꢃ 2, 6H), 2.16 (s, Ar-CH3 ꢃ 2, 6H), 3.91 (s,
ArCH2Ar ꢃ 2, 4H), 3.96 (s, ArCH2Ar, 2H), 4.28 (s, –OCH2CO– ꢃ 2, 4H),
4.61 (s, –OCH2CO– ꢃ 2, 4H), 6.63 (d, J ¼ 1.5 Hz, Ar-H ꢃ 2, 2H), 6.75
(d, J ¼ 8.0 Hz, Ar-H ꢃ 2, 2H), 6.77 (d, J ¼ 1.5 Hz, Ar-H ꢃ 2, 2H), 6.86
(d, J ¼ 1.5 Hz, Ar-H ꢃ 2, 2H), 6.95 (dd, J ¼ 1.5, 8.0 Hz, Ar-H ꢃ 2, 2H).
13C NMR (DMSO-d6) ꢀ 20.5, 20.8, 29.3, 29.4, 65.2, 70.0, 111.9, 127.9,
128.9, 129.3, 129.6, 129.8, 131.4, 133.3, 133.4, 133.5, 152.9, 153.8, 170.5,
170.7. Elemental Analysis Calcd for C39H40O12: C, 66.85; H, 5.75. Found:
C, 66.59; H, 6.06.
General Procedure for the Preparation of 4
To a suspention of 3 (4 mmol) in dry benzene (40–200 mL) was added
thionyl chloride (40 mmol for 3a, 80 mmol for 3b, 120 mmol for 3c,

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PHENOL–FORMALDEHYDE OLIGOMERS
3845
150 mmol for 3d) at room temperature over 1 h. After the addition was
completed, the mixture was stirred at 50ꢀC for 3 h. Removal of benzene
and excess thionyl chloride by rotary evaporator gave 4 as pale yellow
crystals. The product is instability on the purification process. Therefore,
4 were used at next step without further purification.
4a: The yield 98%. M.p. 68–71ꢀC. IR (KBr) 1809 (ꢁCO) cmꢁ1. Fab-
1
mass m/z 185 (MþH)þ. H NMR (CDCl3) ꢀ 2.30 (s, Ar-CH3, 3H), 4.92 (s,
–OCH2CO, 2H), 6.80 (m, Ar-H ꢃ 2, 2H), 7.11 (m, Ar-H ꢃ 2, 2H). 13C NMR
(CDCl3) ꢀ 20.5, 72.9, 114.7, 130.2, 132.2, 154.8, 170.4.
4b: The yield 98%. M.p. 110–113ꢀC. IR (KBr) 1822 (ꢁCO) 1801 (ꢁCO
)
cmꢁ1. Fab-mass m/z 381 (MþH)þ. 1H NMR (CDCl3) ꢀ 2.17 (s, Ar-CH3 ꢃ 2,
6H), 3.92 (s, ArCH2Ar, 2H), 4.83 (s, –OCH2CO ꢃ 2, 4H), 6.55 (d,
J ¼ 8.0 Hz, Ar-H ꢃ 2, 2H), 6.88 (d, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 6.89 (dd,
J ¼ 2.0, 8.0 Hz, Ar-H ꢃ 2, 2H). 13C NMR (CDCl3) ꢀ 20.5, 29.8, 73.0,
111.5, 127.6, 131.9, 152.7, 170.3.
4c: The yield is 95%. M.p. 99–104ꢀC. IR (KBr) 1801 (ꢁCO) cmꢁ1. Fab-
1
mass m/z 577 (MþH)þ. H NMR (CDCl3) ꢀ 2.19 (s, Ar-CH3, 3H), 2.24 (s,
Ar-CH3 ꢃ 2, 6H), 3.97 (s, ArCH2Ar ꢃ 2, 4H), 4.52 (s, –OCH2CO–, 2H), 4.81
(s, –OCH2CO– ꢃ 2, 4H), 6.63 (d, J ¼ 8.0Hz, Ar-H ꢃ 2, 2H), 6.71 (s,
Ar-H ꢃ 2, 2H), 6.88 (d, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 6.98 (dd, J ¼ 2.0,
8.0 Hz, Ar-Hꢃ 2, 2H). 13C NMR (CDCl3) ꢀ 20.5, 20.8, 30.1, 73.0, 76.7, 111.8,
128.0, 129.3, 130.0, 131.8, 132.1, 132.8, 134.6, 151.8, 152.7, 169.7, 170.2.
4d: The yield is 93%. M.p. 101–103ꢀC. IR (KBr) 1805 (ꢁCO) cmꢁ1
.
Fab-mass m/z 774 (MþH)þ. H NMR (CDCl3) ꢀ 2.20 (s, Ar-CH3 ꢃ 2, 6H),
2.24 (s, Ar-CH3 ꢃ 2, 6H), 3.97 (s, ArCH2Ar ꢃ 2, 4H), 3.98 (s, ArCH2Ar,
2H), 4.53 (s, –OCH2CO– ꢃ 2, 4H), 4.92 (s, –OCH2CO– ꢃ 2, 4H), 6.64
(d, J ¼ 8.0Hz, Ar-H ꢃ 2, 2H), 6.73 (d, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 6.78 (d,
J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 6.88 (d, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 7.00 (dd,
J ¼ 2.0, 8.0 Hz, Ar-H ꢃ 2, 2H). 13C NMR (CDCl3) ꢀ 20.6, 20.9, 30.1, 30.6,
72.8, 76.6, 111.6, 128.0, 129.0, 129.7, 130.3, 131.7, 132.1, 132.8, 132.9, 134.8,
151.9, 152.6, 169.8, 170.3.
1
General Procedure for the Preparation of 6a and 6b
To a mixture of L-phenyl alanine methyl ester (1.0 mmol for 4a,
2.0 mmol for 4b) and pridine (1.5 mmol for 4a, 3.0 mmol for 4b) in dry
chloroform (10 mL) was added a solution of 4 (0.5 mmol) in dry chloroform
(10 mL) at 0ꢀC over 1 h. After the addition was complete, the mixture was
stirred at room temperature for 24 h. The reaction mixture was washed with
10% HCl aqueous solution and water. The organic layer was dried over
anhydrous sodium sulfate. Removal of solvent gave oily residue, which was

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3846
ITO, TAKASAWA, AND OHBA
subjected to column chromatography on silica gel using hexane: ethyl acetate
1 : 2 as an eluent to give 6 as colorless crystals.
6a: The yield is 30%. M.p. 68–71ꢀC. IR (KBr) 3415 (ꢁNH), 1751 (ꢁCO),
1
1664 (ꢁCO) cmꢁ1. Fab-mass m/z 327 (MþH)þ. H NMR (CDCl3) ꢀ 2.30 (s,
Ar-CH3, 3H), 3.14 (d, J ¼ 6.0 Hz, CH2Ph, 2H), 3.72 (s, CO2Me, 3H), 4.94
(td, J ¼ 6.0, 8.4 Hz, NCHR, 1H), 6.30–6.80 (m, Ar-H ꢃ 2, 2H), 6.98–7.12 (m,
Ar-H ꢃ 2, Ph-H ꢃ 2 and NH, 5H), 7.21-7.26 (m, Ph-H ꢃ 3, 3H). 13C NMR
(CDCl3) ꢀ 20.5, 37.9, 52.4, 52.5, 67.4, 114.5, 127.2, 128.6, 129.2, 130.1, 131.4,
135.5, 155.1, 168.1, 171.4. Elemental Analysis Calcd for C19H21NO4ꢂH2O:
C, 66.07; H, 6.71; N, 4.06. Found: C, 66.36; H, 6.83; N, 3.55.
6b: The yield is 80%. M.p. 48–50ꢀC. IR (KBr) 3411 (ꢁNH), 1747 (ꢁCO),
1
1687 (ꢁCO) cmꢁ1. Fab-mass m/z 666 (MþH)þ. H NMR (CDCl3) ꢀ 2.16 (s,
Ar-CH3 ꢃ 2, 6H), 2.80 (dd, J ¼ 7.5, 14.0 Hz, CHHPh ꢃ 2, 2H), 2.99 (dd,
J ¼ 5.0, 14.0 Hz, CHHPh ꢃ 2, 2H), 3.61 (s, CO2Me ꢃ 2, 6H), 3.75 (s,
ArCH2Ar, 2H), 4.31 (d, J ¼ 14.5 Hz, –OCHHCO– ꢃ 2, 2H), 4.39 (d, J ¼
14.5 Hz, –OCHHCO– ꢃ 2, 2H), 4.78 (ddd, J ¼ 5.0, 7.5, 8.0 Hz,
NCHR ꢃ 2, 2H), 6.60 (d, J ¼ 8.0 Hz, Ar-H ꢃ 2, 2H), 6.73 (d, J ¼ 2.0 Hz,
Ar-H ꢃ 2, 2H), 6.76 (d, J ¼ 8.0 Hz, NH ꢃ 2, 2H), 6.88–6.93 (m, Ar-H ꢃ 2,
and Ph-H ꢃ 4, 6H) 7.04-7.07 (m, Ph-H ꢃ 6, 6H). 13C NMR (CDCl3) ꢀ 20.6,
30.2, 37.8, 52.3, 52.7, 67.5, 111.7, 127.0, 128.0, 128.3, 128.5, 129.0, 131.1,
131.4, 135.6, 153.0, 168.2, 171.4. Elemental Analysis Calcd for
C39H42N2O8ꢂ0.2(H2O): C, 69.88; H, 6.38; N, 4.18. Found: C, 69.61; H,
6.48; N, 4.10.
General Procedure for the Preparation of 5c and 5d
To a solution of 3 (1.0 mmol) in DMF (20 mL) was added pentafluor-
ophenol (3.3 mmol for 3c, 4.4 mmol for 3d) and ethyl acetate (3 mL). After
cooloing the mixture to 0ꢀC in an ice-bath, a solution of N,N-dicyclohexyl-
carbodiimide (3.3 mmol for 3c, 4.4 mmol for 3d) in DMF (5 mL) was added
over 15 min at 0ꢀC. After the addition was completed, the mixture was
allowed to stir at 0ꢀC for 1 h. The resulting precipitate was removed by
filtration. The filtrate was condensed by rotary evaporator gave colorless
oily residue, which was subjected to column chromatography on silica gel
using hexane : ethyl acetate 3 : 1 as an eluent to give 5 as colorless crystals.
5c: The yield is 86%. M.p. 161–162ꢀC. IR (KBr) 1803 (ꢁCO) cmꢁ1
.
Fab-mass m/z 1020 (MþH)þ. H NMR (CDCl3) ꢀ 2.14 (s, Ar-CH3, 3H),
2.25 (s, Ar-CH3 ꢃ 2, 6H), 4.07 (s, ArCH2Ar ꢃ 2, 4H), 4.70 (s, –OCH2CO–,
2H), 4.96 (s, –OCH2CO– ꢃ 2, 4H), 6.73 (d, J ¼ 8.2 Hz, Ar-H ꢃ 2, 2H), 6.78
(s, Ar-H ꢃ 2, 2H), 6.94 (d, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 7.02 (dd, J ¼ 2.0,
8.2 Hz, Ar-H ꢃ 2, 2H). 13C NMR (CDCl3) ꢀ 20.6, 20.8, 29.7, 64.9, 68.9,
1

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3847
111.4, 124.4, 127.9, 129.7, 131.7, 131.8, 133.0, 134.4, 136.9, 138.7, 140.0,
140.6, 142.0, 152.4, 153.1, 165.3, 165.3. Elemental Analysis Calcd for
C47H27O9F15: C, 55.31; H, 2.67. Found: C, 55.18; H, 2.55.
5d: The yield is 66%. M.p. 176–178ꢀC. IR (KBr) 1799 (ꢁCO) cmꢁ1
.
Fab-mass m/z 1365 (MþH)þ, 1387 (MþNa)þ. H NMR (CDCl3) ꢀ 2.16 (s,
Ar-CH3 ꢃ 2, 6H), 2.24 (s, Ar-CH3 ꢃ 2, 6H), 4.08 (s, ArCH2Ar ꢃ 2, 4H), 4.12
(s, ArCH2Ar, 2H), 4.70 (s, –OCH2CO– ꢃ 2, 4H), 4.97 (s, –OCH2CO– ꢃ 2,
4H), 6.74 (d, J ¼ 8.5 Hz, Ar-H ꢃ 2, 2H), 6.75 (s, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H),
6.80 (d, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 6.93 (d, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 7.02
(dd, J ¼ 2.0, 8.5 Hz, Ar-H ꢃ 2, 2H). 13C NMR (CDCl3) ꢀ 20.5, 20.9, 29.8, 29.9,
64.9, 68.9, 111.3, 124.4, 127.9, 129.2, 129.7, 130.0, 131.7, 131.8, 133.0, 133.1,
134.6, 136.8, 138.7, 140.0, 140.6, 142.0, 152.4, 153.1, 165.3. Elemental
Analysis Calcd for C39H36O8Cl4: C, 55.44; H, 2.66. Found: C, 55.45; H, 2.75.
1
General Procedure for the Preparation of 6c and 6d
To a solution of L-phenylalanine methyl ester (0.6 mmol for 5c,
0.8 mmol for 5d) and triethyl amine (0.3 mmol) in dry chloroform (5 mL)
was added a solution of 5 (0.1 mmol) in dry chloroform (5 mL) at 0ꢀC over
1 h. After the addition was complete, the mixture was allowed to stir at
room temperature for 12 h. Removal of solvent gave oily residue, which
was subjected to column chromatography on silica gel using hexane : ethyl
acetate 1 : 2 as an eluent to give 6 as colorless crystals.
6c: The yield is 52%. M.p. 42–44ꢀC. IR (KBr) 3411 (ꢁNH), 1743 (ꢁCO),
1685 (ꢁCO) cmꢁ1. Fab-mass m/z 1006 (MþH)þ. 1H NMR (CDCl3) ꢀ 2.13 (s,
Ar-CH3, 3H), 2.22 (s, Ar-CH3 ꢃ 2, 6H), 2.90 (dd, J ¼ 7.0, 14.0 Hz,
CHHPh ꢃ 2, 2H), 2.94 (dd, J ¼ 6.5, 13.5 Hz, CHHPh, 1H), 3.09 (dd,
J ¼ 5.5, 14.0 Hz, CHHPh ꢃ 2, 2H), 3.12 (dd, J ¼ 5.5, 13.5 Hz, CHHPh,
1H), 3.67 (s, CO2Me ꢃ 3, 9H), 3.79 (d, J ¼ 16.0 Hz, ArCHHAr ꢃ 2, 2H),
3.87 (d, J ¼ 16.0 Hz, ArCHHAr ꢃ 2, 2H), 4.18 (s, –OCH2CO–, 2H),
4.37 (d, J ¼ 15.0 Hz, –OCHHCO– ꢃ 2, 2H), 4.42 (d, J ¼ 15.0 Hz,
–OCHHCO– ꢃ 2, 2H), 4.88 (m, –NHCH(CO2Me)– ꢃ 3, 3H), 6.65 (d,
J ¼ 8.0 Hz, Ar-H ꢃ 2, 2H), 6.66 (s, Ar-H ꢃ 2, 2H), 6.79 (d, J ¼ 2.0 Hz,
Ar-H ꢃ 2, 2H), 6.85 (d, J ¼ 8.0 Hz, NH ꢃ 2, 2H), 6.90–6.97 (m, Ph-H ꢃ 6,
6H), 6.98 (dd, J ¼ 2.0, 8.0 Hz, Ar-H ꢃ 2, 2H), 7.00–7.08 (m, Ph-H ꢃ 3, 3H),
7.10–7.17 (m, Ph-H ꢃ 6, 6H), 7.38 (d, J ¼ 8.0 Hz, NH, 1H). 13C NMR
(CDCl3) ꢀ 20.6, 20.9, 29.9, 37.6, 37.9, 52.3, 52.4, 52.7, 52.8, 67.6, 71.2,
111.9, 126.9, 127.0, 128.2, 128.3, 128.4, 128.5, 129.0, 129.1, 129.5, 131.4,
131.5, 132.8, 134.6, 135.6, 135.9, 151.7, 153.0, 168.3, 168.5, 171.5, 171.6.
Elemental Analysis Calcd for C59H63N3O12ꢂ0.5(H2O): C, 69.81; H, 6.26;
N, 4.14. Found: C, 69.69; H, 6.39; N, 4.01.

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3848
ITO, TAKASAWA, AND OHBA
6d: The yield is 67%. M.p. 58–61ꢀC. IR (KBr) 3411 (ꢁNH), 1743 (ꢁCO),
1680 (amid I) cmꢁ1. Fab-mass m/z 1345 (MþH)þ. 1H NMR (CDCl3) ꢀ 2.13 (s,
Ar-CH3 ꢃ 2, 6H), 2.23 (s, Ar-CH3 ꢃ 2, 6H), 2.93 (dd, J ¼ 6.0, 13.5 Hz,
CHH ꢃ 2, 2H), 2.95 (dd, J ¼ 6.0, 13.5 Hz, CHH ꢃ 2, 2H), 3.10 (dd, J ¼ 6.0,
13.5 Hz, CHH ꢃ 2, 2H), 3.12 (dd, J ¼ 6.0, 13.5 Hz, CHH ꢃ 2, 2H), 3.65 (s,
CO2Me ꢃ 2, 6H), 3.67(s, CO2Me ꢃ 2, 6H), 3.79(d, J ¼ 16.0 Hz, ArCH2Ar ꢃ 2,
2H), 3.83 (d, J ¼ 16.0 Hz, ArCH2Ar ꢃ 2, 2H), 3.85 (s, ArCH2Ar, 2H), 4.10 (d,
J ¼ 15.0 Hz, –OCHHCO– ꢃ 2, 2H), 4.17 (d, J ¼ 15.0 Hz, –OCHHCO– ꢃ 2,
2H), 4.38 (d, J ¼ 15.0 Hz, –OCHHCO– ꢃ 2, 2H), 4.43 (d, J ¼ 15.0 Hz,
–OCHHCO– ꢃ 2, 2H), 4.84–4.90 (m, –NCH– ꢃ 4, 4H), 6.66–6.80 (m,
Ar-H ꢃ 6, 6H), 6.80 (d, J ¼ 2.0 Hz, Ar-H ꢃ 2, 2H), 6.89 (d, J ¼ 8.0 Hz,
NH ꢃ 2, 2H), 6.97–7.00 (m, Ar-H ꢃ 6, 6H), 7.04–7.10 (m, Ar-H ꢃ 10, 10H),
7.12–7.15 (m, Ar-H ꢃ 6, 6H), 7.36 (d, J ¼ 8.0 Hz, NH ꢃ 2, 2H). 13C NMR
(CDCl3) ꢀ 20.5, 20.6, 20.8, 20.9, 29.8, 29.9, 37.6, 37.8, 52.3, 52.4, 52.4, 52.6,
52.7, 52.8, 52.9, 67.7, 71.4, 111.8, 126.9, 127.0, 128.1, 128.3, 128.4, 128.5,
129.0, 129.1, 129.2, 129.7, 131.3, 131.4, 132.7, 132.8, 134.7, 135.6, 135.9, 151.8,
153.0, 168.2, 171.5, 171.7. Elemental Analysis Calcd for C79H84N4O16ꢂ(H2O):
C, 69.59; H, 6.36, N, 4.11. Found: C, 69.65; H, 6.42; N, 4.07.
ACKNOWLEDGMENT
Authors wish to express sincere thanks to emeritus professor Tyo Sone
(Yamagata University) for his useful suggestions.
REFERENCES
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Supramolecular Chemistry; Stoddart, J.F., Ed.; Royal Society of
Chemistry: London, 1998.
2. (a) Casiragi, G.; Cornia, M.; Sartori, G.; Casnati, G.; Bocchi, V.;
Andreetti, G.D. Makromol. Chem. 1982, 183, 2611; (b) Paulus, E.;
Bohmer, V. Makromol. Chem. 1984, 185, 1921; (c) Dhawan, B.;
Gutsche, C.D. J. Org. Chem. 1983, 48, 1536.
3. (a) Sone, T.; Ohba, Y.; Yamazaki, Y. Bull. Chem. Soc. Jpn. 1989, 62,
1111; (b) Ohba, Y.; Moriya, K.; Sone, T. Bull. Chem. Soc. Jpn. 1991, 64,
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PHENOL–FORMALDEHYDE OLIGOMERS
3849
4. Arena, G.; Casnati, A.; Contino, A.; Sciotto, D.; Ungaro, R.
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Received in Japan September 13, 2001

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