Synthesis of new chiral calix[4]azacrowns for enantiomeric recognition of carboxylic acids

Article abstract of DOI:10.1016/j.tetasy.2008.08.015

Two novel chiral calix[4]azacrown ethers 4 and 5 bearing a furfuryl group on the nitrogen atom were developed by the reaction of dibromo- or ditosyl derivatives of p-tert-butylcalix[4]arenes 2 and 3 with a chiral diol, 1. The enantioselective recognition of these receptors towards the enantiomers of racemic carboxylic acids has been studied by ¹H NMR spectroscopy. The molar ratio and the association constants of the chiral compounds 4 and 5 with each of the enantiomers of guest molecules were determined by using Job plots and a nonlinear least-squares fitting method, respectively. The Job plots indicate that both of the hosts form 1:1 instantaneous complexes with (R)- or (S)-mandelic acid and (l)- or (d)-dibenzoyltartaric acid. The receptors exhibited different chiral recognition abilities towards the enantiomers of racemic guests.

Full text of DOI:10.1016/j.tetasy.2008.08.015

Tetrahedron: Asymmetry 19 (2008) 2020–2025
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of new chiral calix[4]azacrowns for enantiomeric recognition
of carboxylic acids
*
Havva Nur Demirtas, Selahattin Bozkurt, Mustafa Durmaz, Mustafa Yilmaz, Abdulkadir Sirit
Department of Chemistry, Selçuk University, 42099 Konya, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
Two novel chiral calix[4]azacrown ethers 4 and 5 bearing a furfuryl group on the nitrogen atom were
developed by the reaction of dibromo- or ditosyl derivatives of p-tert-butylcalix[4]arenes 2 and 3 with
a chiral diol, 1. The enantioselective recognition of these receptors towards the enantiomers of racemic
carboxylic acids has been studied by 1H NMR spectroscopy. The molar ratio and the association constants
of the chiral compounds 4 and 5 with each of the enantiomers of guest molecules were determined by
using Job plots and a nonlinear least-squares fitting method, respectively. The Job plots indicate that both
Received 16 June 2008
Accepted 18 August 2008
Available online 8 September 2008
of the hosts form 1:1 instantaneous complexes with (R)- or (S)-mandelic acid and (L)- or (D)-dibenzoyl-
tartaric acid. The receptors exhibited different chiral recognition abilities towards the enantiomers of
racemic guests.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Among the several types of host molecules for recognition,
calixarenes8 offer a number of advantages in terms of their selec-
Chiral recognition is an essential phenomenon in biological sys-
tems such as enzymes, antibodies or genes.1 In this process, the
functional groups of molecular receptors form complexes preferen-
tially with one of the enantiomers of a chiral molecule by noncova-
lent interactions such as hydrogen bonding, electrostatic
interaction and hydrophobic interaction.2
Several approaches have already been developed for the evalu-
ation of chiral recognition, including spectroscopic, chromato-
graphic and electrochemical techniques. Among them, NMR
spectroscopy has been shown to be a powerful method for investi-
gating the chiral recognition interaction between a chiral receptor
and an analyte in solution.3 Detailed information regarding the
nature of these interactions and the structure of the complexes
can also be provided from NMR experiments. NMR spectra of enan-
tiomers in an achiral medium display the same chemical shifts.
Enantiodifferentiation in the spectra requires the use of a chiral
medium that converts the mixture of enantiomers into a mixture
of diastereomeric complexes. These complexes are held together
by weak intermolecular interactions such as van der Waals forces
and/or hydrogen bonds.4
tivity and efficiency of binding. Despite the increasing use of calix-
arenes as receptors for anions, cations and neutral molecules,9
relatively few investigations have been reported for chiral guests
such as amines,10 organic ammonium salts,11 amino alcohols,12
carboxylic acids13 and amino acids.14 The most frequently used
strategies for introducing chiral recognition ability into calixarenes
are anchoring chiral subunits at either the lower or the upper rims
of the calixarene macrocyclic ring. Chiral receptors that are based
on the calixarene platform may have potential applications in the
preparation, separation and analysis of enantiomers. In this regard,
investigations conducted on the synthesis and chiral recognition
properties of chiral calix[4]arene derivatives have attracted consid-
erable attention.
Previously, we had reported the synthesis of novel chiral
calix[4]arenes containing various functionalities including crown15
and azacrown ethers,16 amides,17 Schiff bases,18 as well as their
enantiomeric recognition properties towards chiral amines and
amino acid derivatives. Herein, we report the synthesis of novel
calix[4]arene derivatives bearing a chiral azacrown-5 moiety at
the lower rim, and their recognition abilities for racemic mandelic
and dibenzoyltartaric acid by 1H NMR spectroscopy.
Chiral carboxylic acids are the basic building blocks of many
natural products, biological molecules and drugs. Therefore, the
study of the enantiomeric recognition of these compounds is of
particular significance for an understanding of the interactions
between biological molecules,5 and offer new perspectives for
the development of novel enantioselective sensors, asymmetric
catalysts6 and other molecular devices.7
2. Results and discussion
2.1. Synthesis
Calix[4]azacrowns containing a calix[4]arene platform and an
azacrown unit in their framework have received much attention
because of their special structures and favourable complexing
* Corresponding author. Tel.: +90 332 3238220/5405; fax: +90 332 3238225.
E-mail address: asirit42@yahoo.com (A. Sirit).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.08.015

H. N. Demirtas et al. / Tetrahedron: Asymmetry 19 (2008) 2020–2025
2021
properties towards anions and cations.19 The basicity of the nitro-
gen atom in the azacrown loop can also play a major role in the
enantioselective recognition of carboxylic acids. Thus, a suitably
designed chiral calix[4]azacrown derivative might be a good candi-
date. This can be realized by incorporating a chiral azacrown ether
moiety as a binding site into the molecular framework of a
calix[4]arene. A multistep route for preparing the furfuryl-armed
calix[4]azacrown ethers is shown in Schemes 1 and 2.
CDCl3 until the ratio reached 1:1, the methine proton signals of
mandelic acid separated into two singlets with an upfield shift.
The chemical shift differences were determined to be 0.24 and
0.29 ppm for compound 4 (Fig. 1d), and 0.21 and 0.28 ppm for
compound 5 (Fig. 1e), respectively. A similar phenomenon was ob-
served when a solution of racemic dibenzoyltartaric acid (10 mM
in CDCl3) was treated with an equimolar amount of receptors 4
and 5 (Fig. 2), the methine proton signals of dibenzoyltartaric acid
separated into two singlets with an upfield shift (from d 6.01 ppm
to 5.93 and 5.92 ppm for 4, and to 5.97 and 5.96 ppm for 5). The
Thus, following the literature procedure,20 one of the starting
materials, chiral diol 1, was prepared by the ring opening of the
(R)-styrene oxide with furfuryl amine in high yield. The furfuryl-
armed calix[4]azacrowns were obtained in 41 and 53% yields by
the reaction of the p-tert-butylcalix[4]arene derivatives 221 or 322
with chiral amino diol 1 in DMF.
methine proton of (S)-mandelic acid and
appeared at lower field than that of (R)-mandelic acid and
enzoyltartaric acid, which was confirmed by an increase of the
methine proton signal of (S)- and -guest when (S)-mandelic acid
and -dibenzoyltartaric acid were added into the complex of race-
mic guests with 4 or 5.
D-dibenzoyltartaric acid
L
-dib-
D
The products were characterized by a combination of 1H NMR,
13C NMR, FAB MS, IR and elemental analysis. The conformational
characteristics of calix[4]arenes were conveniently estimated by
way of the splitting pattern of the ArCH2Ar methylene protons in
the 1H and 13C NMR spectra. 1H and 13C NMR data showed that chi-
ral p-tert-butylcalix[4]arene derivatives 4 and 5 are in a cone
conformation.
D
The stoichiometry of the complexes between the receptors 4
and 5 and the guests was determined by a continuous variation
plot. The total concentration of the hosts and the guest was kept
constant (10 mM) in CDCl3, whilst the molar fraction of the guest
{[G]/([H]+[G])} was continuously varied. The Job plots of 4 with
(R)- and (S)-mandelic acid and L- and D-dibenzoyltartaric acid are
illustrated in Figures 3 and 4, respectively. Maxima were observed
2.2. Chiral recognition by 1H NMR of host–guest complexes
when the molar ratio of the compound 4 and (R)- or (S)-mandelic
Next, NMR experiments were undertaken to assess the chiral
recognition properties of ligands 4 and 5 by 1H NMR, and the race-
mic guests, mandelic acid and dibenzoyltartaric acid were chosen
as probes. The signal of the methine hydrogen of mandelic acid
and dibenzoyltartaric acid is a sharp singlet and does not overlap
with the peaks of the other proton signals in their 1H NMR spectra.
Therefore, it is an ideal probe for discrimination.
acid and L- or D-dibenzoyltartaric acid was 1:1 (X = 0.5), which
indicated that host 4 and the guests formed 1:1 instantaneous
complexes. It is apparent that the chemical shift changes of (R)-
mandelic acid and
D-dibenzoyltartaric acid were greater than that
of corresponding enantiomers (S)-mandelic acid and
L
-dibenzoyl-
tartaric acid in the presence of compound 4. Meanwhile, all Job
plots recorded for 5 indicated that 1:1 instantaneous complexes
were also formed with all these enantiomerically pure guests,
respectively.
In order to further evaluate the complexation and discrimina-
tion abilities of 4 and 5, the titration curves of compounds 4 and
Figure 1 shows the 1H NMR spectra for mandelic acid (10 mM)
in the absence and presence of the chiral receptors 4 and 5
(10 mM). When a solution of racemic mandelic acid (10 mM in
CDCl3) was gradually added to a 10 mM solution of 4 and 5 in
Ph
O
O
Methanol
70 ºC, 5 h
NH2
+
N
O
OH
OH
1
Scheme 1. Preparation of amino diol 1.
O
O
N
N
R
R
O
O
O
O
O
OR'
OH
OMe
O
O
O
O
O
OR'
OH
OMe
i
ii
4
2: R = Br, R' = H
3:
5
R = OTs, R' = Me
Scheme 2. Reagents: (i)–(ii) Chiral amino diol 1, NaH, DMF, reflux.

2022
H. N. Demirtas et al. / Tetrahedron: Asymmetry 19 (2008) 2020–2025
Figure 1. The 400 MHz 1H NMR spectra of the racemic mandelic acid (a); 4 (b); 5
(c); and the complexes between 4 and 5 (10 mM) and racemic mandelic acid
(10 mM) in CDCl3 (d); (e).
Figure 2. The 400 MHz 1H NMR spectra of the ( )-dibenzoyltartaric acid (a); 4 (b);
5 (c); and the complexes between 4 and 5 (10 mM) and ( )-dibenzoyltartaric acid
(10 mM) in CDCl3 (d); (e).
5 with the enantiomers of mandelic acid or dibenzoyltartaric acid
were plotted, respectively (Figs. 5 and 6). It was found that the sig-
nals of the methine protons of (R)- and (S)-mandelic acids or
L
D- and
-dibenzoyltartaric acids in the 1H NMR spectra continuously
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
shifted upfield and reached a limiting value along with the concen-
tration of compounds 4 and 5 gradually increasing. Moreover, the
signals of various protons of the hosts were shifted downfield.
These shifts are due to specific host–guest complexation, and indi-
cated that the interaction between the host and guest also hap-
pened by multiple hydrogen bonds.
The formation of diastereomeric host–guest complexes possibly
occurs through interaction of the nitrogen atom in the azacrown
loop and the carboxyl group in the chiral carboxylic acid. Noncova-
lent interactions between the guests and hydrogen bonding sites
defined by ethylene oxygens, furan oxygen and phenolic oxygen
0.0
0.2
0.4
0.6
0.8
1.0
X
contribute to the stabilization of these complexes as well as
p–p
Figure 3. Job plots of 4 with (R)- and (S)-mandelic acid [X = molar fraction of
mandelic acid, d = chemical shift change of the methine proton of (R)- and (S)-
mandelic acid]. (j) With pure (R)-mandelic acid, (N) with pure (S)-mandelic acid.
interactions. The association constants of 4 and 5 with enantiome-
rically pure guests were determined from the titration curves by
the nonlinear least-squares fitting method23 (Table 1). The results
D
showed that (R)- and
L-enantiomers of the guests were more
strongly bound to 4 and 5 than (S)- and
D
-enantiomers. Moreover,
carboxylic acids we had chosen. The chiral receptors (4 and 5)
are structurally similar in that both contain a group capable of
hydrogen bonding as part of a stereogenic centre attached directly
to a phenyl group. Though the number of recognition sites that are
necessary for producing chiral recognition is due to the shape of
the receptor, three ordinary recognition sites are required in the
receptor molecules.24 In this study, chiral calix[4]crowns 4 and 5
the binding ability of host compounds with mandelic acid was
much stronger than that with dibenzoyltartaric acid. This con-
firmed further that enantioselective recognition had occurred be-
tween receptors 4 and 5 and the racemic guests.
From Table 1, we found that both compounds had shown good
chiral recognition ability towards the enantiomers of the racemic

H. N. Demirtas et al. / Tetrahedron: Asymmetry 19 (2008) 2020–2025
2023
groups and phenolic oxygens) in order to exhibit enantioselective
binding to the mandelic acid and dibenzoyltartaric acid.
According to Table 1, we also found that compounds 4 and 5
had shown much better chiral recognition ability to mandelic acid
than to dibenzoyltartaric acid. Among the guest molecules, man-
0.1
0.08
0.06
0.04
0.02
0
delic acid contains a hydroxy group at the
a-position of the car-
bonyl group. This oxygen function may act as an additional
binding site and play a crucial role for chiral recognition.5a Since
the methine protons are adjacent to the hydroxy group, these pro-
tons must be significantly influenced by the possible recognition
groups of the chiral calix[4]azacrown derivative.
0
0.2
0.4
0.6
0.8
1
X
3. Conclusions
Figure 4. Job plots of 4 with
L
- and
D
-dibenzoyltartaric acid [X = molar fraction of
- and
-dibenzoyltartaric acid, (N) with pure
dibenzoyltartaric acid, d = chemical shift change of the methine proton of
D
L
In conclusion, two novel chiral calix[4]azacrown ethers in
which a furfuryl group is attached on the nitrogen atom were
synthesized by the reaction of dibromo- or ditosyl derivatives of
p-tert-butylcalix[4]arene with a chiral diol. The enantioselective
recognition of these receptors has been studied by 1H NMR
spectroscopy. The receptors exhibited different chiral recognition
abilities towards the enantiomers of racemic mandelic acid and
dibenzoyltartaric acid. The stoichiometric ratio of the host–guest
complexes was determined as 1:1 instantaneous complexes
according to Job’s method of continuous variations. The results
indicate that the multiple hydrogen bonding, steric hindrance,
D-dibenzoyltartaric acid]. (j) With pure
L
D-dibenzoyltartaric acid.
5.2
5.16
5.12
5.08
5.04
5
(S)-Mandelic acid
(R)-Mandelic acid
structural rigidity or flexibility and
matic groups may be responsible for the enantiomeric recognition.
p p stacking between the aro-
ꢀ
4. Experimental
0
0.01
0.02
0.03
0.04
0.05
CH mol/l
4.1. Reagents and general methods
Figure 5. 1H NMR titration curves of compound 4 with (R)- and (S)-mandelic acids.
Melting points were determined on an Electrothermal 9100
apparatus in a sealed capillary, and are uncorrected. 1H and 13C
NMR spectra were recorded at room temperature on a Varian
400 MHz spectrometer in CDCl3. IR spectra were obtained on a Per-
kin Elmer 1605 FTIR spectrometer using KBr pellets. Optical rota-
tions were measured on an Atago AP-100 digital polarimeter. The
HPLC measurements were carried out on Agilent 1100 equipment
connected with a Zorbax RX-C18 column. Elemental analyses were
performed using a Leco CHNS-932 analyzer. FAB-MS spectra were
taken on a Varian MAT 312 spectrometer.
Analytical TLC was performed using Merck prepared plates (Sil-
ica Gel 60 F254 on aluminium). Flash chromatography separations
were performed on a Merck Silica Gel 60 (230–400 mesh). All reac-
tions, unless otherwise noted, were conducted under a nitrogen
atmosphere. All starting materials and reagents used were of stan-
dard analytical grade from Fluka, Merck and Aldrich, and were
used without further purification. Toluene was distilled from
CaH2 and stored over sodium wire. Other commercial grade sol-
vents were distilled, and then stored over molecular sieves. The
drying agent employed was anhydrous MgSO4.
6.05
D-dibenzoyltartaric acid
6
L-dibenzoyltartaric acid
5.95
5.9
5.85
5.8
0
0.01
0.02
0.03
0.04
0.05
CH mol/l
Figure 6. 1H NMR titration curves of compound 4 with (
taric acids.
L
)- and (D)-dibenzoyltar-
Table 1
Association constants Ka (mol/L)ꢀ1 of 4 and 5 with chiral carboxylic acids
Entry
Host
Guests
Ka (mol/L)ꢀ1
Ka (R or L)/Ka (S or D)
4.2. Syntheses
1
2
3
4
5
6
7
8
4
4
4
4
5
5
5
5
(R)-Mandelic acid
(S)-Mandelic acid
(1.27 0.07) ꢂ 103
(0.68 0.05) ꢂ 103
(2.92 0.26) ꢂ 102
(2.34 0.19) ꢂ 102
(1.03 0.08) ꢂ 103
(0.72 0.06) ꢂ 103
(1.98 0.24) ꢂ 102
(1.79 0.19) ꢂ 102
1.86
1.25
1.43
1.11
4.2.1. (R,R)-2-[Furfuryl-(2-hydroxy-2-phenylethyl)-amino]-1-
phenylethanol 1
L-DBTA
D-DBTA
(R)-Mandelic acid
(S)-Mandelic acid
To a cooled solution of furfurylamine (1.07 g, 9.985 mmol) in
2 mL of methanol, (R)-styrene oxide (2.40 g, 19.975 mmol) in
4 mL of methanol was added at 0 °C and stirred for 1 h. It was then
refluxed for 4 h. After the completion of the reaction, the solvent
was removed under reduced pressure to give isomeric diols as syr-
upy mass which on flash column chromatography using ethylace-
tate/hexane (20:80) as eluent yielded the major isomer as an oil
L-DBTA
D-DBTA
interact with a minimum of three of the possible recognition
groups (ethylene oxygens, amine nitrogen, furan oxygen, aromatic
(yield 86%); ½a 2D5
¼ ꢀ72 (c 1, CHCl3). IR (KBr): 3342, 3281, 3102,
ꢁ

2024
H. N. Demirtas et al. / Tetrahedron: Asymmetry 19 (2008) 2020–2025
2994, 2826, 1490, 1368, 1350, 1275, 1174, 1060, 726 cmꢀ1
;
1H
4.4. Evaluation of the stoichiometric ratio of the host–guest
complex (Job plots)
NMR (400 MHz, CDCl3): (ppm) 7.32 (dd, 1H, J1 = 1.7 Hz,
d
J2 = 0.8 Hz, ArH, furfuryl), 7.26–7.19 (m, 10H, ArH), 6.27 (dd, 1H,
J1 = 3.3 Hz, J2 = 1.8 Hz, ArH, furfuryl), 6.16 (dd, 1H, J1 = 3.3 Hz,
J2 = 0.6 Hz, ArH, furfuryl), 4.68 (dd, 2H, J1 and J2 = 4.7 Hz, –CH-
phenyl), 4.34 (2H, br s, –OH), 3.85 (d, 1H, J = 15.1 Hz, NCH2-fur-
furyl), 3.78 (d, 1H, J = 15.1 Hz, NCH2-furfuryl), 2.74–2.68 (m, 4H,
NCH2CH); 13C NMR (100 MHz, CDCl3): d (ppm): 146.2, 144.1,
143.4, 128.3, 127.4, 125.2, 113.9, 105.1, 72.5, 63.9, 54.1; FAB-MS
m/z: (360.28) [M+Na]+. Anal. Calcd for C21H23NO3 (337.41): C,
74.75; H, 6.87; N, 4.15. Found: C, 74.52; H, 6.96; N, 3.98.
The stoichiometric ratio of the host–guest complex was deter-
mined according to Job’s method of continuous variations.25 Equi-
molar amounts of host and guest compounds were dissolved in
CDCl3. These solutions were distributed among nine NMR tubes,
with the molar fractions X of host and guest in the resulting solu-
tions increasing (or decreased) from 0.1 to 0.9 (and vice versa). The
compellation-induced shifts (Dd) were multiplied by X and plotted
against X itself (Job plot).
4.5. NMR host–guest titrations
4.2.2. General procedure for the synthesis of compounds
4 and 5
The guest compound was dissolved in an appropriate amount of
solvent and the resulting solution evenly distributed among 10
NMR tubes. The first NMR tube was sealed without any host. The
host compound was also dissolved in the appropriate amount of
solvent and was added in increasing amounts to the NMR tubes,
so that solutions with the following relative amounts (equiv) of
host versus guest compound (concentration was 1.0 ꢂ 10ꢀ2 M)
were obtained: 0, 0.20, 0.40, 0.60, 0.80, 1.00, 1.20, 1.50, 2.00,
2.50, 3.50 and 4.50. Ka was calculated by a nonlinear least-squares
To a suspension of NaH (60% in mineral oil) 0.14 g (3.56 mmol)
in DMF (3 mL) was added a solution of 1 0.31 g (0.89 mmol) in DMF
(5 mL) dropwise at 0 °C under a nitrogen atmosphere. The mixture
was stirred at room temperature for 2 h. Then 2 or 3 (0.89 mmol) in
DMF (20 mL) was added slowly to the mixture. The mixture was
stirred at room temperature for 2 days. The DMF extract was evap-
orated and water (10 mL) was added to the remaining residue. The
mixture was extracted with CH2Cl2 (3 ꢂ 10 mL) and combined
organic phase was dried over MgSO4. The solvent was evaporated
and the crude product was purified by flash chromatography on
silica gel (EtOAc/hexane 1:15 as eluent) to afford 4 or 5 as white
crystals.
fitting method for compounds 4 and 5 from the observed
Dd values
and the respective host and guest concentrations.
Acknowledgements
4.2.2.1. Compound 4.
Yield 41%; white crystal; Mp 114–
¼ þ17 (c 1, CHCl3). IR (KBr): 3422, 2961, 2866, 1486,
1H NMR (400 MHz,
118 °C; ½a 2D5
ꢁ
This work was supported by the Scientific and Technical Re-
search Council of Turkey (TUBITAK-106T091) and Research Foun-
dation of Selçuk University (BAP-06401067). The provision of
studentships (to H.D. and M.D.) by TUBITAK is gratefully
acknowledged.
1458, 1362, 1198, 1120, 1025, 872, 701 cmꢀ1
;
CDCl3): d (ppm) 7.36–6.95 (m, 17H, ArH and ArOH), 6.72–6.68
(m, 4H, ArH), 6.16 (dd, 1H, J1 = 3.3 Hz, J2 = 0.6 Hz, ArH, furfuryl),
5.91 (d, 1H, J = 3.1 Hz, ArH, furfuryl), 4.39 (d, 2H, J = 12.9 Hz, ArCH2-
Ar), 4.35 (d, 2H, J = 12.9 Hz, ArCH2Ar), 4.22 (t, 2H, J = 5.4 Hz,
–OCHph), 4.03–3.93 (m, 4H, –OCH2CH2), 3.71–3.63 (m, 2H, phCH2N),
3.57–3.51 (m, 4H, –OCH2CH2), 3.25 (d, 2H, J = 13.1 Hz, ArCH2Ar),
3.23 (d, 2H, J = 13.1 Hz, ArCH2Ar), 3.03 (d, 4H, J = 5.7 Hz, –CHCH2N),
1.25 (s, 18H, C(CH3)3), 0.84 (s, 18H, C(CH3)3); 13C NMR (100 MHz,
CDCl3): d (ppm): 154.3, 151.3, 150.4, 146.8, 142.0, 141.6, 141.1,
132.8, 128.5, 127.5, 125.7, 125.2, 110.2, 107.9, 82.6, 75.5, 67.3,
61.8, 53.0, 34.5, 34.1, 32.1, 31.7, 31.6, 31.3; FAB-MS m/z:
(1061.22) [M+Na]+. Anal. Calcd for C69H83NO7 (1038.40): C,
79.81; H, 8.06; N, 1.35. Found: C, 80.06; H, 8.57; N, 1.19.
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4.2.2.2. Compound 5.
Yield 53%; white crystal; Mp 113–
116 °C; ½a 2D5
ꢁ
¼ ꢀ6:0 (c 1, CHCl3). IR (KBr): 2962, 2866, 1482,
1362, 1203, 1121, 1023, 870, 700 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d (ppm) 7.36–7.22 (m, 15H, ArH), 6.75–6.69 (m, 4H, ArH), 6.16 (br,
1H, ArH, furfuryl), 5.94 (br, 1H, ArH, furfuryl), 4.48 (br, 2H, ArCH2-
Ar), 4.44 (br, 2H, ArCH2Ar), 4.20 (t, 2H, J = 5.4 Hz, –OCHph), 4.08–
3.96 (m, 4H, –OCH2CH2), 3.90 (br, 6H, –OCH3), 3.72–3.65 (m, 2H,
phCH2N), 3.60–3.53 (m, 4H, –OCH2CH2), 3.10–3.20 (m, 4H, ArCH2-
Ar), 3.00 (br, 4H, –CHCH2N), 1.22 (br, 18H, C(CH3)3), 1.08–0.90 (br,
18H, C(CH3)3); 13C NMR (100 MHz, CDCl3): d (ppm): 155.2, 151.3,
150.8, 146.9, 142.4, 141.6, 132.9, 127.3, 125.6, 125.2, 110.2,
108.0, 82.6, 74.7, 67.6, 61.1, 52.4, 34.3, 34.1, 32.3, 31.9, 31.5,
31.2, 22.6; FAB-MS m/z: (1089.30) [M+Na]+. Anal. Calcd for
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