Preparation of optically active azophenolic crown ethers containing 1-phenylethane-1,2-diol and 2,4-dimethyl-3-oxapentane-1,5-diol as a chiral subunit: Temperature-dependent enantiomer selectivity in the complexation with chiral amines

Article abstract of DOI:10.1039/a703452k

With (2S,4S)-2,4-dimethyl-3-oxapentane-1,5-diol and (S)- or (R)-1-phenylethane-1,2-diol as chiral subunits, optically active azophenolic crown ethers (S,S,S,S)-1, (R,S,S,R)-2, (S,S,S,S)-3 and (R,S,S,R)-4 possessing two phenyl and two methyl substituents together with the p-(2,4-dinitrophenylazo)phenol moiety have been prepared in enantiomerically pure forms. Temperature-dependent enantiomer selectivity in the complexation of these crown ethers with chiral amines has been studied by the UV-visible spectroscopic method in chloroform and from the observed association constants, thermodynamic parameters for the complexation have been calculated.

Full text of DOI:10.1039/a703452k

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Preparation of optically active azophenolic crown ethers containing
1-phenylethane-1,2-diol and 2,4-dimethyl-3-oxapentane-1,5-diol as a
chiral subunit: temperature-dependent enantiomer selectivity in the
complexation with chiral amines1
Kazuko Ogasahara, Keiji Hirose, Yoshito Tobe and Koichiro Naemura*
Department of Chemistry, Faculty of Engineering Science, Osaka University, Toyonaka,
Osaka 560 Japan
With (2S,4S)-2,4-dimethyl-3-oxapentane-1,5-diol and (S)- or (R)-1-phenylethane-1,2-diol as chiral
subunits, optically active azophenolic crown ethers (S,S,S,S)-1, (R,S,S,R)-2, (S,S,S,S)-3 and (R,S,S,R)-4
possessing two phenyl and two methyl substituents together with the p-(2,4-dinitrophenylazo)phenol
moiety have been prepared in enantiomerically pure forms. Temperature-dependent enantiomer selectivity
in the complexation of these crown ethers with chiral amines has been studied by the UV–visible
spectroscopic method in chloroform and from the observed association constants, thermodynamic
parameters for the complexation have been calculated.
Complexation of chiral and achiral molecular receptors
possessing a well-defined three-dimensional cavity with guests
has been widely studied,2 while complexation of chiral crown
ethers of an 18-crown-6 type possessing a planar binding cavity
are still of interest for obtaining basic information on chiral
recognition behaviour. We have prepared optically active crown
ethers of this type by using various types of chiral subunits,
examined the enantiomer recognition behaviour in complex-
ation with chiral amines and given an explanation for the
observed enantiomer selectivities on the basis of CPK molecular
model examination.3 Recently, we found that the sign of the
Me
Me
Me
Me
O
O
Ph
Ph
O
O
O
O
Ph
Ph
O
O
O
O
OH
OH
N
N
Ar
N
N
Ar
∆
R,S∆G values for the complexation of the azophenolic crown
ethers with 2-aminopropan-1-ol in CDCl3 reversed at ca. 6 ЊC;
the enantiomer selectivities observed at the ordinary temper-
ature were governed by Ϫ∆R,S∆S.4 The facts show that it is
important to know whether the observed enantiomer selectivity
in complexation is governed by Ϫ∆R,S∆H or Ϫ∆R,S∆S in order
to discuss structural complementarity between a chiral crown
ether and guest enantiomers on the basis of CPK molecular
model examination of complexes and the observed enantiomer
selectivity. Herein, we report the preparation of the optically
active azophenolic crown ethers (S,S,S,S)-1, (R,S,S,R)-2,
(S,S,S,S)-3 and (R,S,S,R)-4 by using (S)- or (R)-1-phenyl-
ethane-1,2-diol and (2S,4S)-2,4-dimethyl-3-oxapentane-1,5-
diol as a chiral subunit. These crown ethers contain the phenol
moiety which possesses an intraannular OH group as a binding
site for neutral amines and the 2,4-dinitrophenylazo group at
the para-position which is not only a chromophore but also
increases the binding ability of the compounds towards a
neutral amine.5 Their enantiomer selectivities in complexation
with chiral amines were evaluated at various temperatures by
the UV–visible spectroscopic method in CHCl3 and from the
observed association constants, thermodynamic parameters for
the complexation were calculated.
(S,S,S,S)-1
(R,S,S,R)-2
Me
Me
Me
Me
O
O
O
O
O
O
O
O
Ph
O
OH
O
Ph
OH
Ph
Ph
N
N
Ar
N
N
Ar
(S,S,S,S)-3
(R,S,S,R)-4
to give (S)-6, the THP blocking group of which was then
removed to give (S)-7 in 72% overall yield. Condensation of
(S)-7 with racemic ethyl 2-bromopropionate in the presence of
sodium hydride gave 8 as a mixture of (S,S)- and (S,R)-
diastereoisomers in 51% yield. After hydrogenolysis of 8 with
H2 and 10% Pd on carbon in ethanol, the resulting diol 9 was
tosylated to give a 1:1 mixture of (S,S)-10 and (S,R)-10, the 1H
NMR spectrum of which exhibited two doublet signals of
equal intensity due to the methyl groups at δ 1.04 and 1.07 for
(S,S)-10 and (S,R)-10, respectively. The mixture was recrystal-
lized from methanol until the signal at δ 1.07 disappeared com-
pletely to give diastereoisomerically and enantiomerically pure
(S,S)-10 in 19% yield based on 8.
Results and discussion
The chiral diethylene glycol unit (S,S)-106 was prepared from
ethyl (S)-lactate. According to a published route,7 by protection
of the hydroxy group as a tetrahydropyranyl ether (THP) fol-
lowed by LiAlH4 reduction, ethyl (S)-lactate was transformed
to (S)-5 in 90% yield. The primary hydroxy group of (S)-5 was
blocked by treatment with benzyl chloride and sodium hydride
The chiral subunits (S)-11 and (R)-11 were prepared from
J. Chem. Soc., Perkin Trans. 1, 1997
3227

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Me
Ph
Ph
Me
Me
Me
Me
R1O
OR2
O
O
HO
OTHP HO
OTHP
OH
OTs
Me
RO
TsO
(R)-11
(S)-5 R1 = H R2 = THP
8 R = CH2Ph
9 R = H
(S,S)-10
(S)-11
(S)-6 R1 = CH2Ph R2 = THP
(S)-7 R1 = CH2Ph R2 = H
Me
Me
Me
R2
R1
R2
R1
R1
R2
R1
R2
O
O
OTHP
O
THPO
OH
O
HO
O
R2
R1
R2
R1
R1
R2
R1
R2
O
O
O
O
O
O
O
O
OMe
OMe
OMe
O
OH
OMe
OMe
OMe
OMe
(S,S)-12 R1 = Ph R2 = H
(R,R)-13 R1 = H R2 = Ph
(S,S)-14 R1 = Ph R2 = H
(R,R)-15 R1 = H R2 = Ph
(S,S,S,S)-16 R1 = Ph R2 = H
(R,S,S,R)-17 R1 =H R2 = Ph
(S,S,S,S)-18 R1 = Ph R2 = H
(R,S,S,R)-19 R1 = H R2 = Ph
Me
Me
Me
Me
O
O
Me
Me
Me
Me
O
O
O
O
O
O
O
O
R2
R1
R2
R1
R2
R1
R2
R1
O
O
O
O
O
O
OMe
OMe
OH
R2
R1
R2
R1
R2
R1
R2
R1
OTHP THPO
OH
HO
OMe
(S,S,S,S)-26 R1 = Ph R2 = H
(R,S,S,R)-27 R1 = H R2 = Ph
1 = Ph R2 = H
(S,S,S,S)-22 R1 = Ph R2 = H
(R,S,S,R)-23 R1 = H R2 = Ph
(S,S,S,S)-24 R1 = Ph R2 = H
(R,S,S,R)-25 R1 = H R2 = Ph
(S,S,S,S)-20 R
(R,S,S,R)-21 R1 = H R2 = Ph
(S)- and (R)-mandelic acid, respectively, according to a pub-
lished route:5,8 esterification, protection of the hydroxy group
and LiAlH4 reduction.
unit. Condensation of 2 mol equiv. of (S)-11 with (S,S)-10 in
the presence of sodium hydride in DMF followed by removal of
the blocking group gave (S,S,S,S)-22 in 28% overall yield via
(S,S,S,S)-20. High-dilution condensation of (S,S,S,S)-22 with
1,3-bis(bromomethyl)-2,5-dimethoxybenzene in the presence of
sodium hydride and potassium tetrafluoroboranuide in DMF
gave (S,S,S,S)-24 in 36% yield. The inner methoxy group of
(S,S,S,S)-24 was cleaved to give (S,S,S,S)-26, which was trans-
formed to (S,S,S,S)-3 in 55% overall yield by oxidation with
CAN followed by treatment with 2,4-dinitrophenylhydrazine.
In a similar manner, condensation of 2 mol equiv. of (R)-11
with (S,S)-10 followed by deprotection gave (R,S,S,R)-23 in
21% overall yield, which was transformed to (R,S,S,R)-4 in 21%
overall yield via (R,S,S,R)-25 and (R,S,S,R)-27, successively.
The association constants for the complexes of the crown
ethers (S,S,S,S)-1, (R,S,S,R)-2, (S,S,S,S)-3 and (R,S,S,R)-4
with chiral amines (2-aminopropan-1-ol 28, 2-amino-3-
methylbutan-1-ol 29, 2-amino-2-phenylethan-1-ol 30, 1-amino-
propan-2-ol 31 and 1-phenylethylamine 32) were determined at
various temperatures by the Rose–Drago method11 on the basis
of the absorption in UV–visible spectrum of the complexes; the
crown ethers showed an absorption maximum at 400–406 nm in
chloroform and that of the complexes with amines appeared in
the region 560–580 nm. The Ka values for the complexes of
(S,S,S,S)-1 with (R)-28, (R)-30 and (R)-31 were so large at 4 ЊC
that it was difficult to get accurate data; these were, therefore,
evaluated over the temperature range 15–45 ЊC. The observed
Ka values of the complexes and thermodynamic parameters for
the complexation calculated from the Ka values are summarized
in Table 1. The predictive isoenantioselective temperatures
(Tiso = ∆R,S∆H/∆R,S∆S) are also calculated and listed in Table 1.
The preparation of (S,S,S,S)-1 having C-5 and C-13 phenyl
substituents and homotopic faces was carried out stepwise; that
is, condensation of (S)-11 with a m-phenylene unit and then
ring closure with a chiral diethylene glycol unit. Treatment of 2
mol equiv. of (S)-11 with 1,3-bis(bromomethyl)-2,5-dimethoxy-
benzene in the presence of sodium hydride in tetrahydrofuran
(THF) gave (S,S)-12, which was deprotected with methanol
containing a small amount of hydrochloric acid to give (S,S)-14
in 57% overall yield. High-dilution condensation of (S,S)-14
with (S,S)-10 in the presence of sodium hydride and potassium
tetrafluoroboranuide in N,N-dimethylformamide (DMF) gave
(S,S,S,S)-16 in 37% yield. For easy conversion of the
dimethoxyphenyl moiety to the p-benzoquinone moiety, the
inner methoxy group of (S,S,S,S)-16 was selectively cleaved by
treatment with sodium ethanethiolate in DMF9 to give
(S,S,S,S)-18 in 80% yield. Oxidation of (S,S,S,S)-18 with
cerium() ammonium nitrate (CAN) in acetonitrile10 followed
by treatment with 2,4-dinitrophenylhydrazine in a mixture of
conc. H2SO4, ethanol and methylene dichloride gave (S,S,S,S)-
1 in 81% overall yield. By the same sequence of the reactions
described above, (R,R)-15 was derived from (R)-11 and 1,3-
bis(bromomethyl)-2,5-dimethoxybenzene in 58% overall yield
via (R,R)-13. Ring closure of (R,R)-15 with (S,S)-10 gave
(R,S,S,R)-17, which was transformed to (R,S,S,R)-2 in 31%
overall yield via (R,S,S,R)-19.
For the preparation of (S,S,S,S)-3 having C-4 and C-14
phenyl groups, two chiral subunits (S)-11 were first linked with
a chiral diethylene glycol unit and then with a m-phenylene
3228
J. Chem. Soc., Perkin Trans. 1, 1997

Table 1 Association constants for the complexes and thermodynamic parameters for complexation of crown ethers in CHCl3
Ka/molϪ1
Crown
ether
∆H
∆S
Amine
at 4 ЊC
at 15 ЊC
at 25 ЊC
at 38 ЊC
at 45 ЊC
kJ molϪ1
J degϪ1 molϪ1
Tiso a/ЊC
b
(S,S,S,S)-1
(S,S,S,S)-1
(S,S,S,S)-1
(S,S,S,S)-1
(S,S,S,S)-1
(S,S,S,S)-1
(S,S,S,S)-1
(S,S,S,S)-1
(S,S,S,S)-1
(S,S,S,S)-1
(R,S,S,R)-2
(R,S,S,R)-2
(R,S,S,R)-2
(R,S,S,R)-2
(R,S,S,R)-2
(R,S,S,R)-2
(R,S,S,R)-2
(R,S,S,R)-2
(R,S,S,R)-2
(R,S,S,R)-2
(S,S,S,S)-3
(S,S,S,S)-3
(S,S,S,S)-3
(S,S,S,S)-3
(S,S,S,S)-3
(S,S,S,S)-3
(S,S,S,S)-3
(S,S,S,S)-3
(S,S,S,S)-3
(S,S,S,S)-3
(R,S,S,R)-4
(R,S,S,R)-4
(R,S,S,R)-4
(R,S,S,R)-4
(R,S,S,R)-4
(R,S,S,R)-4
(R,S,S,R)-4
(R,S,S,R)-4
(R,S,S,R)-4
(R,S,S,R)-4
(R)-28
(S)-28
(R)-29
(S)-29
(R)-30
(S)-30
(R)-31
(S)-31
(R)-32
(S)-32
(R)-28
(S)-28
(R)-29
(S)-29
(R)-30
(S)-30
(R)-31
(S)-31
(R)-32
(S)-32
(R)-28
(S)-28
(R)-29
(S)-29
(R)-30
(S)-30
(R)-31
(S)-31
(R)-32
(S)-32
(R)-28
(S)-28
(R)-29
(S)-29
(R)-30
(S)-30
(R)-31
(S)-31
(R)-32
(S)-32
(2.64 0.50) × 104
(3.69 0.24) × 103
(3.54 0.29) × 103
(6.02 0.21) × 102
(1.20 0.07) × 104
(7.32 0.30) × 102
(1.58 0.23) × 104
(6.08 1.41) × 103
(2.61 0.35) × 102
(7.20 0.17) × 102
(2.85 0.16) × 103
(8.80 0.73) × 103
(4.30 0.16) × 102
(2.17 0.21) × 103
(1.03 0.05) × 103
(8.31 0.21) × 103
(3.49 0.18) × 103
(7.45 0.32) × 103
(6.83 0.18) × 102
(2.56 0.28) × 102
(8.89 0.30) × 103
(3.75 0.18) × 103
(1.99 0.09) × 103
(1.69 0.03) × 103
(2.26 0.13) × 103
(7.13 0.09) × 102
(6.94 0.57) × 103
(2.46 0.21) × 103
(3.66 0.03) × 102
(3.54 0.11) × 102
(1.62 0.10) × 103
(3.68 0.24) × 103
(3.71 0.47) × 102
(6.98 0.26) × 102
(2.20 0.22) × 102
(9.70 0.21) × 102
(1.58 0.07) × 103
(3.20 0.16) × 103
(2.91 0.17) × 102
(1.96 0.13) × 102
(1.04 0.35) × 104
(1.57 0.09) × 103
(1.59 0.16) × 103
(2.94 0.33) × 102
(4.47 1.16) × 103
(3.00 0.21) × 102
(5.96 1.29) × 103
(2.54 0.16) × 103
(1.44 0.03) × 102
(4.05 0.12) × 102
(1.69 0.42) × 103
(4.71 1.82) × 103
(2.15 0.11) × 102
(9.48 0.25) × 102
(3.80 0.43) × 102
(2.91 0.19) × 103
(1.50 0.27) × 103
(3.11 0.07) × 103
(3.08 0.13) × 102
(1.22 0.10) × 102
(3.19 0.15) × 103
(1.59 0.07) × 103
(8.19 0.66) × 102
(6.11 0.30) × 102
(9.84 0.57) × 102
(3.65 0.23) × 102
(3.98 0.11) × 103
(1.68 0.19) × 103
(2.02 0.11) × 102
(1.80 0.05) × 102
(5.92 0.20) × 102
(1.13 0.86) × 103
(1.94 0.11) × 102
(3.22 0.09) × 102
(1.09 0.02) × 102
(4.32 0.66) × 102
(6.13 0.70) × 102
(1.42 0.07) × 103
(1.45 0.09) × 102
(9.3 0.4) × 10
(2.99 0.31) × 103
(4.77 0.55) × 102
(4.73 0.58) × 102
(1.05 0.11) × 102
(1.38 0.12) × 102
(1.20 0.03) × 102
(1.98 0.11) × 103
(7.91 0.90) × 102
(4.7 0.2) × 10
(1.53 0.12) × 103
(2.53 0.33) × 102
Ϫ70.5 6.8
Ϫ66.4 7.9
Ϫ78.2 0.7
Ϫ61.4 0.6
Ϫ75.7 6.2
Ϫ63.1 6.5
Ϫ70.6 4.3
Ϫ68.4 9.2
Ϫ53.5 5.4
Ϫ57.7 10.5
Ϫ59.9 2.8
Ϫ65.8 1.4
Ϫ54.7 0.4
Ϫ64.6 0.3
Ϫ60.9 9.3
Ϫ66.1 10.0
Ϫ60.2 10.6
Ϫ71.5 3.1
Ϫ59.6 4.3
Ϫ54.0 5.6
Ϫ61.5 2.4
Ϫ54.4 2.9
Ϫ58.6 0.3
Ϫ53.0 0.5
Ϫ56.3 4.6
Ϫ50.8 5.9
Ϫ56.3 3.6
Ϫ44.4 3.5
Ϫ47.8 3.3
Ϫ47.8 3.7
Ϫ57.4 7.5
Ϫ61.3 7.8
Ϫ54.5 0.6
Ϫ66.0 1.1
Ϫ53.0 1.7
Ϫ62.0 1.2
Ϫ63.7 15
Ϫ58.4 8.4
Ϫ49.6 2.4
Ϫ49.1 2.9
Ϫ160 22
Ϫ162 26
—
(1.74 0.05) × 104
(1.75 0.10) × 103
Ϫ202
Ϫ159
2
2
124
356
(5.89 0.54) × 102
(5.8 0.3) × 10
Ϫ183 20
Ϫ164 21
Ϫ165 14
Ϫ165 30
Ϫ139 18
Ϫ145 36
Ϫ141 10
b
(8.51 0.31) × 102
(3.72 0.78) × 102
—
(6.19 0.19) × 102
(1.74 0.17) × 103
(8.80 0.64) × 103
(3.11 0.15) × 104
(1.08 0.04) × 103
(6.64 0.51) × 103
(2.80 0.21) × 103
(2.33 0.13) × 104
(8.95 0.66) × 103
(2.76 0.27) × 104
(1.78 0.04) × 103
(5.83 0.15) × 102
(2.43 0.24) × 104
(9.07 0.99) × 103
(5.04 0.22) × 103
(2.69 0.11) × 103
(5.67 0.15) × 103
(1.68 0.08) × 103
(1.80 0.26) × 104
(5.29 0.55) × 103
(8.23 0.19) × 102
(7.52 0.19) × 102
(3.35 0.24) × 103
(7.91 0.36) × 103
(8.65 0.45) × 102
(1.82 0.11) × 103
(4.70 0.17) × 102
(2.40 0.04) × 103
(3.25 0.17) × 103
(6.89 0.60) × 103
(6.72 0.32) × 102
(4.39 0.07) × 102
412
263
205
(1.07 0.04) × 102
(5.17 0.35) × 102
(1.40 0.16) × 103
(7.6 0.5) × 10
Ϫ152
Ϫ139
Ϫ160
5
1
1
(2.92 0.20) × 102
(1.55 0.08) × 102
(9.91 0.25) × 102
(5.33 0.67) × 102
(9.41 0.15) × 102
(1.12 0.08) × 102
(4.8 0.6) × 10
b
Ϫ154 32
Ϫ155 34
Ϫ141 36
Ϫ173 11
Ϫ153 15
Ϫ142 19
—
81
230
131
93
(1.38 0.12) × 103
(7.04 0.39) × 102
(3.26 0.35) × 102
(2.24 0.21) × 102
(4.10 0.24) × 102
(1.53 0.12) × 102
(1.23 0.05) × 103
(6.28 0.36) × 102
(8.7 0.4) × 10
Ϫ138
8
Ϫ120 10
Ϫ141
Ϫ125
1
2
Ϫ131 16
Ϫ122 20
Ϫ122 12
Ϫ89 12
Ϫ116 11
Ϫ117 13
Ϫ138 26
Ϫ145 27
296
90
b
—
(8.1 0.5) × 10
(2.81 0.26) × 102
(5.88 0.30) × 102
(7.3 0.7) × 10
288
57
Ϫ140
Ϫ174
Ϫ139
Ϫ157
2
4
6
4
(9.1 2.7) × 10
(4.7 0.4) × 10
209
Ϫ61
(1.62 0.7) × 102
(1.98 0.24) × 102
(5.22 0.42) × 102
(6.3 0.3) × 10
Ϫ162 52
Ϫ137 28
b
Ϫ125
8
—
(4.3 0.1) × 10
Ϫ126 10
a The predictive isoenantioselective temperatures are calculated from ∆H and ∆S values. b The Tiso value was not calculated because of the small ∆∆S value.

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Fig. 1 Temperature dependence of ln(KR/KS) for the complexation of
2-aminopropan-1-ol 28 with crown ethers; ᭜ (S,S,S,S)-1, ᭡ (R,S,S,R)-
2, ᭿ (S,S,S,S)-3 and × (R,S,S,R)-4
Fig. 3 Temperature dependence of ln(KR/KS) for the complexation of
2-amino-2-phenylethanol 30 with crown ethers; ᭜ (S,S,S,S)-1, ᭡
(R,S,S,R)-2, ᭿ (S,S,S,S)-3 and × (R,S,S,R)-4
Fig. 4 Temperature dependence of ln(KR/KS) for the complexation of
1-aminopropan-2-ol 31 with crown ethers; ᭜ (S,S,S,S)-1, ᭡ (R,S,S,R)-
2, ᭿ (S,S,S,S)-3 and × (R,S,S,R)-4
Fig. 2 Temperature dependence of ln(KR/KS) for the complexation of
2-amino-3-methylbutan-1-ol 29 with crown ethers; ᭜ (S,S,S,S)-1, ᭡
(R,S,S,R)-2, ᭿ (S,S,S,S)-3 and × (R,S,S,R)-4
Me
Me
HO
H
(Me)2HC
H2N
H
Ph
H
H
H2N
OH
OH
H2N
OH
NH2
(S)-29
(S)-30
(S)-31
(S)-28
H
(Me)2HC
H2N
H
Me
Ph
H2N
(R)-32
Ph
H
H
H2N
OH
H
OH
Me
H2N
OH
(R)-28
(R)-29
(R)-30
Me
H
Ph
HO
NH2
Me
H2N
(S)-32
(R)-31
Fig. 5 Temperature dependence of ln(KR/KS) for the complexation of
1-phenylethylamine 32 with crown ethers; ᭜ (S,S,S,S)-1, ᭡ (R,S,S,R)-
2, ᭿ (S,S,S,S)-3 and × (R,S,S,R)-4
In Figs. 1, 2, 3, 4 and 5, we have plotted ln(KR/KS) values of
complexation for the amines 28, 29, 30, 31 and 32, respectively,
with the four crown ethers as a function of temperature. The
enantiomer selectivities for formation of the (S,S,S,S)-1:28, the
(S,S,S,S)-1:31, the (S,S,S,S)-3:32 and the (R,S,S,R)-4:32
complexes scarcely changed during the experiment. On the
other hand, in all the other combinations of the crown ether
and the amine, unambiguous temperature-dependent enantio-
mer selectivities were observed. The plot in Fig. 4 shows that
the S-selectivity of (R,S,S,R)-4 towards 31 increased with
increasing temperature over the experimental temperature; the
Tiso value is calculated to be Ϫ61 ЊC.
The crown ethers (S,S,S,S)-1 and (S,S,S,S)-3 showed R-
selectivity towards the 2-substituted 2-aminoethanol derivatives
28, 29 and 30 whilst the crown ethers having the R,S,S,R-
configuration showed S-selectivity towards these amines. Since
these selectivities, except for that of (S,S,S,S)-1 towards 28, are
obviously found below Tiso (governed by Ϫ∆R,S∆H), we explain
these selectivities in terms of steric interactions between the
steric barriers of the crown ether and the ligands of the amine.
On the basis of CPK molecular model examination of the
complexes and with the assumptions12 that the phenolate
3230
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
Me
Me
Me
Me
Me
Me
Me
Me
O
O
O
H
O
+
O
O
O
O
O
+
O
O
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
+
H
H
H
H
H
H
H
H
H
H
H
H
Ph
+
Ph
H2C
CH2
H2C
O
CH2
O
H
O
H
H
O
O
O
–
O–
O–
– HO
OH
OH
HO
NO2
NO2
NO2
NO2
NO2
N
N
NO2
N
N
N
N
NO2
N
N
NO2
35
36
34
33
Me
Me
Me
Me
Me
Me
Me
Me
H
O
O
O
O
+
+
O
O
O
O
O
O
O
O
O
+
H
H
H
H
H
H
H
H
H
+
H2C
H
H2C
CH2
CH2
H
Ph
H
O–
Ph
H
O–
H
O–
H
O
Ph
Ph
O
Ph
O
O
Ph
O
O
O
O
Ph
Ph
OH
OH
HO
– OH
NO2
NO2
NO2
NO2
NO2
N
N
N
N
NO2
NO2
N
N
N
N
NO2
38
40
39
37
oxygen atom necessarily participates in binding to an amine
and the hydroxymethyl group of 2-aminoethanol derivatives
occupies preferentially the site near the phenol moiety making
the additional hydrogen bonding between the phenolate oxygen
atom and the hydroxy group, the predicted geometries 33, 34,
35 and 36 are illustrated for the (S,S,S,S)-1:(R)-30, the
(S,S,S,S)-1:(S)-30, the (R,S,S,R)-2:(R)-30 and the (R,S,S,R)-
2:(S)-30 complexes, respectively. Judging from the steric
requirements of CPK molecular models of the complexes of
(S,S,S,S)-1 and the observed enantiomer selectivities, we assume
that the area over the hydrogen atom at the 12 o’clock position
is the less hindered site and that the C-5 phenyl substituent
occupies a pseudo-equatorial position; this makes the C-4
methylene and the C-5 methine groups effective chiral barriers.
‘The ethyleneoxy barrier’ (shaded ellipse in the geometries)
functions as the more effective chiral barrier on the β-face of
the complex compared with the C-13 phenyl substituent (open
ellipse in the geometries). Similarly, the C-13 methine and the
C-14 methylene groups serve as ‘the ethyleneoxy barrier’ in the
complexes of (R,S,S,R)-2.
With the assumptions described above, the R-selectivity of
the combination (S,S,S,S)-1:30 is interpreted as arising from
steric repulsion between ‘the ethyleneoxy barrier’ and the
hydroxymethyl group of (S)-30 and making the (S,S,S,S)-
1:(S)-30 complex with the geometry 34 less stable than the
(S,S,S,S)-1:(R)-30 complex. The S-selectivity of the combin-
ation (R,S,S,R)-2:30 is analogously rationalized; the (R,S,S,R)-
2:(R)-30 complex with the geometry 35 was destabilized by
steric repulsion between ‘the ethyleneoxy barrier’ and the
hydroxymethyl group of the amine.
The predicted geometries 37, 38, 39 and 40 are illustrated for
the (S,S,S,S)-3:(R)-30, the (S,S,S,S)-3:(S)-30, the (R,S,S,R)-
4:(R)-30 and the (R,S,S,R)-4:(S)-30 complexes, respectively.
On the basis of the steric requirements of CPK molecular
models of the complexes of (S,S,S,S)-3, it is assumed that the
pseudo-equatorial C-14 phenyl substituent makes the C-13
methylene and the C-14 methine groups ‘the ethyleneoxy bar-
rier’; but the phenyl substituent at C-4 position is the more
effective chiral barrier on the β-face of the complex and thus
plays a more important role in chiral discrimination. The R-
selectivities of the combination (S,S,S,S)-3:30 is interpreted as
arising from steric repulsion between the C-4 phenyl chiral
barrier and the hydroxymethyl group of (S)-30 and thus
making the (S,S,S,S)-3-(S)-30 complex with the geometry 38
less stable than the (S,S,S,S)-3-(R)-30 complex. Analogously,
steric repulsion between the C-14 phenyl chiral barrier and the
hydroxymethyl group of (R)-30 made the (R,S,S,R)-4:30 com-
plex with the geometry 39 less stable than the (R,S,S,R)-4:(S)-
30 complex.
Fig. 4 demonstrates that the most stable complexes for
(R,S,S,R)-2 and (S,S,S,S)-3 were formed with (S)-31 and with
(R)-31, respectively, below Tiso. Although the S-selectivity of the
combination (R,S,S,R)-4:31 was found above Tiso, it is not
clear whether the R-selectivity of the combination (S,S,S,S)-
1:31 was observed above or below Tiso. The predicted geom-
etries 41, 42, 43 and 44 where the hydroxymethyl group occu-
pies the less hindered site near the phenolate oxygen atom are
illustrated for the (R,S,S,R)-2:(R)-31, the (R,S,S,R)-2:(S)-31,
the (S,S,S,S)-3:(R)-31 and the (S,S,S,S)-3:(S)-31 complexes,
respectively. It is assumed that the S-selectivity of the combin-
ation (R,S,S,R)-2:31 is due to steric repulsion between the
methyl group of (R)-31 and the phenyl substituent which
destabilizes the (R,S,S,R)-2:(R)-31 complex, whilst steric repul-
sion between the methyl group of (S)-31 and ‘the ethyleneoxy
barrier’ made the (S,S,S,S)-3:(S)-31 complex less stable than
its diastereoisomeric complex.
In the case of complexation with 32, the S-selectivity of
(S,S,S,S)-1 and the R-selectivity of (R,S,S,R)-2 were unam-
biguously found below Tiso. The predicted geometries 45, 46, 47
and 48 are illustrated for the (S,S,S,S)-1:(S)-32, the (S,S,S,S)-
1:(R)-32, the (R,S,S,R)-2:(S)-32 and the (R,S,S,R)-2:(R)-32
complexes, respectively. It is assumed that steric repulsion
between the ‘ethyleneoxy barrier’ and the methyl group of 32
made the (S,S,S,S)-1:(R)-32 and the (R,S,S,R)-2:(S)-32 com-
plexes less stable than the corresponding diastereoisomeric
complexes.
As mentioned here, the results demonstrated that arrange-
ment of substituents on the crown ether ring affects enantiomer
selectivity: the enantiomer selectivities of the crown ethers
having the phenyl substituents located near the diethylene
glycol bridge were higher than those of the crown ethers having
the same substituents located near the phenol moiety.
Experimental
General procedure
1H NMR spectra were recorded at 270 MHz on a JASCO
JNM-MH-270 spectrometer for solutions in CDCl3 with
J. Chem. Soc., Perkin Trans. 1, 1997
3231

View Article Online
Me
Me
Me
H
Me
Me
Me
Me
H
Me
O
H
O
H
O
H
O
H
O
O
O
O
O
O
O
O
O
Ph
O
+
O
O
Ph
+
+
Ph
+
Ph
H
H
H
H
H
H
H
H
H
H
H
O
Me
O
Me
O
H
O
H
H
Me
Me
O–
H
Ph
H
Ph
Ph
Ph
O– HO
–
OH
–
OH
HO
O
O
NO2
NO2
NO2
Me
NO2
NO2
N
N
NO2
N
N
N
N
NO2
N
N
NO2
Me
41
43
44
42
Me
Me
Me
Me
Me
Me
Me
Me
O
O
O
O
H
O
O
O
O
Ph
O
O
O
O
O
O
O
O
O
O
Ph
+
+
Ph
Ph
+
Ph
+
H
Ph
Ph
H
H
H
H
H
H
H
H
H
Ph
Me
Me
H
Me
Me
H
H
O–
H
O–
H
O–
O
O
O–
NO2
NO2
NO2
NO2
NO2
NO2
N
N
N
N
N
N
NO2
N
N
NO2
47
45
46
48
SiMe4 as internal standard and J values are given in Hz. Mass
spectra were recorded on a JEOL-DX-303-HF spectrometer
using m-nitrobenzyl alcohol as a matrix. Elemental analyses
were carried out by Yanagimoto CHN-Corder, Type 2. Mps
were measured on a Yanagimoto micro melting point apparatus
and are uncorrected. UV and visible spectra were recorded on a
Hitachi 330 spectrometer. IR spectra were measured on a
Hitachi 260-10 spectrometer. Optical rotations were measured
using a JASCO DIP-40 polarimeter at ambient temperature
and [α]D-values are given in units of 10Ϫ1 deg cm2 gϪ1. The chiral
amines: (R)-28, (S)-28, (R)-29, (S)-29, (R)-31, (S)-31, (R)-32
and (S)-32 were purchased from Aldrich Chemical Company,
Inc. and (R)-30 from Tokyo Kasei Kogyo Co., Ltd. These
amines were used without further purification. (S)-2-Amino-2-
phenylethanol 30 purchased from Aldrich Chemical Company,
Inc. was used after recrystallization from benzene–hexane.13
ated under reduced pressure to give (S)-6, which was dissolved
in methanol (300 cm3). The solution was stirred with a few
drops of hydrochloric acid for 12 h at room temperature after
which it was neutralized with aq. sodium hydrogen carbonate
and evaporated. The residue was extracted with benzene. The
combined extracts were washed with aq. sodium hydrogen
carbonate and water, dried (MgSO4) and evaporated under
reduced pressure. Distillation of the residue gave (S)-7 (97.8 g,
72%); bp 123–125 ЊC (14 mmHg); [α]2D2 ϩ13.2 (c 1.05, CHCl3);
νmax(neat film)/cmϪ1 3400, 3030, 2975, 2870, 1458, 1370, 1100,
1030, 1000, 965, 855, 742 and 710; δH(CDCl3) 1.14 (3H, d, J 6.4,
CH3), 2.33 (1H, s, OH), 3.29 (1H, dd J 7.9 and 9.4, CH2), 3.46
(1H, dd J 3.2 and 9.4, CH2), 3.95–4.04 (1H, m, CH), 4.51 (2H, s,
benzylic CH2) and 7.25–7.36 (5H, m, C6H5) (Found: C, 72.08;
H, 8.5. C10H14O2 requires C, 72.26; H, 8.49%).
A diastereoisomeric mixture of 2,4-dimethyl-3-oxapentane-
1,5-diol 9
(2S)-2-Tetrahydropyranyloxypropan-1-ol 5
A mixture of ethyl (S)-lactate (100 g, 0.847 mol), 3,4-dihydro-
2H-pyran (142 g, 1690 mol) and a few drops of hydrochloric
acid was stirred at room temperature for 12 h after which it was
washed with aq. sodium hydrogen carbonate and water, dried
(MgSO4) and evaporated under reduced pressure to give oily
products. These, dissolved in dry THF (700 cm3), were added
slowly to a suspension of LiAlH4 (25.0 g, 0.659 mol) in dry
THF (1200 cm3). After the mixture had been refluxed for 4 h, it
was cooled to 0–5 ЊC and diluted with acetone (80 cm3) and
water (10 cm3). Deposited solids were filtered off and the filtrate
was dried (MgSO4) and evaporated under reduced pressure to
give (S)-5 (122 g, 90%) as a mixture of diastereoisomers, which
was used for the next reaction without further purification.
A solution of (S)-7 (45.7 g, 0.275 mol) in dry THF (600 cm3)
was slowly added to a suspension of sodium hydride (7.92 g,
0.330 mol) in dry THF (800 cm3) after which the mixture was
stirred for 3 h under reflux. After the reaction mixture had been
cooled to room temperature, it was treated with ethyl ( )-2-
bromopropionate (100 g, 0.552 mol), added slowly, and then
stirred for 19 h at room temperature. A small amount of water
was carefully added to the reaction mixture with ice-cooling,
after which the volatile materials were evaporated under
reduced pressure. The residue was extracted with chloroform.
The combined extracts were washed with water, dried (MgSO4)
and evaporated under reduced pressure to give oily products,
which were dissolved in dry THF (600 cm3). The THF solution
was added slowly to a suspension of LiAlH4 (16.0 g, 0.422 mol)
in dry THF (1000 cm3) and the mixture was stirred for 24 h at
room temperature. Saturated aq. ammonium chloride was care-
fully added to the reaction mixture with ice-cooling, to give a
solid which was filtered off. The filtrate was evaporated under
reduced pressure and the residue extracted with methylene
dichloride. The combined extracts were washed with water,
dried (MgSO4) and evaporated under reduced pressure to give
oily products, which were distilled to give 8 (62.5 g, 51%); bp
125–127 ЊC (0.4 mmHg). A solution of 8 (61.0 g, 0.272 mol)
and toluene-p-sulfonic acid monohydride (1.00 g, 5.26 mmol) in
ethanol (1000 cm3) was vigorously stirred at room temperature
(2S)-3-Benzyloxypropan-2-ol 7
A solution of (S)-5 (131 g, 0.819 mol) in dry THF (600 cm3) was
carefully added to a suspension of sodium hydride (28.8 g, 1.20
mol) in dry THF (700 cm3) after which the mixture was refluxed
for 1.5 h. After the reaction mixture had been cooled to 0–5 ЊC,
it was treated with benzyl chloride (154 g, 1.22 mol), added
slowly and then refluxed for 32 h. After this, the reaction mix-
ture was treated with a small amount of water, added carefully
with ice-cooling, and then concentrated under reduced pres-
sure. The residue was extracted with chloroform. The combined
extracts were washed with water, dried (MgSO4) and evapor-
3232
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
over 10% Pd-on-carbon (5.80 g) under 1 atm of hydrogen.
After hydrogen uptake had ceased, the catalyst was filtered off.
The filtrate was neutralized with aq. sodium hydrogen carbon-
ate and concentrated under reduced pressure. The residue was
extracted with methylene dichloride and the combined extracts
were washed with water, dried (MgSO4) and evaporated under
reduced pressure to give 9 (35.4 g, 97%) as a mixture of dia-
stereoisomers, which was used for the next reaction without
further purification.
and 7.27–7.40 (10 m, C6H5) (Found: C, 70.88; H, 6.9. C22H30O6
requires C, 71.21; H, 6.90%).
1,3-Bis[(4R)-4-hydroxy-4-phenyl-2-oxabutyl]-2,5-dimethoxy-
benzene 15
In a manner similar to that described for the preparation of
(S,S)-14, reaction of (R)-11 (10.1 g, 0.188 mol) which was pre-
pared from (R)-mandelic acid as a mixture of two diastereo-
isomers8 with 1,3-bis(bromomethyl)-2,5-dimethoxybenzene
(7.41 g, 22.9 mmol) followed by silica gel chromatography of
the products gave (R,R)-13 [hexane–ethyl acetate (2:1)]. Depro-
tection of (R,R)-13 with methanol containing a few drops of
hydrochloric acid gave (R,R)-15 (5.79 g, 58%) after silica gel
chromatography [hexane–ethyl acetate (2:1)]; [α]D25 Ϫ3.73 (c
0.346, CHCl3); νmax(neat film)/cmϪ1 3430, 2902, 1605, 1482,
1250, 1110, 1065, 1012, 908, 765 and 705; δH(CDCl3) 2.86 (2H,
d, J 2.6, OH), 3.56 (2H, dd, J 8.7 and 9.7, OCH2), 3.70 (2H, dd,
J 3.1 and 9.7, OCH2), 3.71 (3H, s, OCH3), 3.78 (3H, s, OCH3),
4.63 (4H, s, benzylic CH2), 4.94 (2H, ddd, J 2.6, 3.1 and 8.7,
CHPh), 6.89 [2H, s, (MeO)2ArH] and 7.28–7.41 (10, m, C6H5)
(Found: Mϩ, 438.2072. C26H30O6 requires M, 438.2042).
(2S,4S)-2,4-Dimethyl-1,5-di-p-tosyloxy-3-oxapentane 10
Toluene-p-sulfonyl chloride (130 g, 0.682 mol) was added to a
solution of 9 (40.8 g, 0.304 mol) in pyridine (220 cm3) at 0–5 ЊC,
after which the mixture was stirred at the same temperature for
3.5 h and then poured into ice–water, acidified (pH 2.0) with
hydrochloric acid and extracted with chloroform. The com-
bined extracts were washed successively with dil. hydrochloric
acid, aq. sodium hydrogen carbonate and water, dried (MgSO4)
and evaporated under reduced pressure to give a white solid,
whose 1H NMR spectrum showed two sets of signals; δH-
(CDCl3) 1.04 [6H, d J 7.3, CH3 for (S,S)-10], 1.07 [6H d J 6.3,
CH3 for (S,R)-10], 2.45 [12H, s, ArCH3 for (S,S)-10 and (S,R)-
10], 3.60–3.85 [6H, m, CH and OCH2 for (S,S)-10], 3.78–3.91
[6H, m, CH and OCH2 for (S,R)-10], 7.32–7.36 [8H, m, ArH for
(S,S)-10 and (S,R)-10] and 7.75–7.80 [8H, m, ArH for (S,S)-10
and (S,R)-10]. The solid was recrystallized seven times from
methanol until the doublet signal at δ 1.07 had disappeared to
give diastereoisometrically and enantiomerically pure (S,S)-10
(26.8 g, 20%); mp 82.0–82.5 ЊC; [α]D29 ϩ3.4 (c 0.990, CHCl3).
HPLC analysis [Opti-Pak XC, 250 mm × 4.6 mm column,
hexane–ethanol (98:2, 0.1 cm3 minϪ1)] showed only a single
peak for (S,S)-10 [Rt/min 59.9], that for (R,R)-10 [Rt/min 67.8]
being absent; νmax(KBr)/cmϪ1 2980, 2960, 2940, 2920, 1595,
1365, 1342, 1200, 1180, 1120, 995, 975, 858, 850, 820, 790, 705
and 665; δH(CDCl3) 1.04 (6H, d, J 7.3, CH3), 2.45 (6H, s,
ArCH3), 3.60–3.82 (2H, m, CH), 3.85 (4H, d, J 5.2, OCH2),
7.34 (4H, d, J 8.4, ArH) and 7.77 (4H, d, J 8.4, ArH) (Found:
C, 54.00; H, 5.8; S, 14.44. C20H26O7S2 requires C, 54.28; H, 5.92;
S, 14.49%).
(5S,8S,10S,13S)-19,21-Dimethoxy-8,10-dimethyl-5,13-diphenyl-
3,6,9,12,15-pentaoxabicyclo[15.3.1]henicosane-1(21),17,19-
triene 16
A solution of (S,S)-14 (660 mg, 1.51 mmol) and (S,S)-10 (705
mg, 1.59 mmol) in dry DMF (150 cm3) was added dropwise to a
mixture of sodium hydride (147 mg, 6.13 mmol) and potassium
tetrafluoroboranuide (228 mg, 1.63 mmol) in dry DMF (150
cm3) over a 9 h period at 90 ЊC, after which the mixture was
heated for further 48 h at the same temperature. After the mix-
ture had been cooled to 0–5 ЊC, it was treated with a small
amount of water and then evaporated under reduced pressure.
The residue was extracted with ethyl acetate and the combined
extracts were washed with water, dried (MgSO4) and evapor-
ated under reduced pressure. The residue was chromato-
graphed on silica gel to give (S,S,S,S)-16 (300 mg, 37%)
[hexane–ethyl acetate (4:1)] as a colourless glass; [α]D22 ϩ143 (c
0.495, CHCl3); νmax(KBr)/cmϪ1 2905, 2895, 2884, 1598, 1475,
1442, 1360, 1238, 1190, 1000, 760 and 700; δH(CDCl3) 0.97 (6H,
d, J 6.4, CH3), 3.18 (2H, dd, J 2.7 and 10.0, OCH2), 3.26 (2H,
dd, J 7.2 and 10.1, OCH2), 3.63–3.68 (6H, m, OCH2 and
CHMe), 3.81 (3H, s, OCH3), 4.06 (3H, s, OCH3), 4.47 (2H, br s,
CHPh), 4.48 (2H, d, J 10.0, benzylic CH2), 4.85 (2H, d, J 10.0,
benzylic CH2), 6.88 [2H, s, (MeO)2ArH] and 7.28–7.36 (10H, m,
C6H5) (Found: Mϩ, 536.2747. C32H40O7 requires M, 536.2774).
1,3-Bis[(4S)-4-hydroxy-4-phenyl-2-oxabutyl]-2,5-dimethoxy-
benzene 14
A solution of (S)-11 {[α]D25 ϩ58.0 (c 1.00, CHCl3); 30.8 g, 139
mmol} which had been prepared from (S)-mandelic acid as the
mixture of two diastereoisomers5 in dry THF (150 cm3) was
slowly added to a suspension of sodium hydride (15.2 g, 0.633
mol) in dry THF (150 cm3). After the mixture had been refluxed
for 1.5 h, it was cooled to room temperature and treated with a
solution of 1,3-bis(bromomethyl)-2,5-dimethoxybenzene (22.3
g, 68.8 mmol) in dry THF (100 cm3). The mixture was refluxed
for 12 h, after which it was treated with a small amount of water
with ice-cooling, and concentrated under reduced pressure. The
residue was extracted with ethyl acetate and the combined
extracts were washed with water, dried (MgSO4) and evapor-
ated under reduced pressure. The residue was chromatographed
on silica gel to give (S,S)-12 (32.3 g, 87%) [hexane–ethyl acetate
(9:1)] as a yellow oil, which was dissolved in methanol (150
cm3). The solution was stirred with a few drops of hydrochloric
acid at room temperature for 12 h and then evaporated under
reduced pressure. The residue was extracted with ethyl acetate.
The combined extracts were washed with aq. sodium hydrogen
carbonate and water, dried (MgSO4) and evaporated under
reduced pressure. The residue was chromatographed on silica
gel to give (S,S)-14 (17.3 g, 65%) [hexane–ethyl acetate (2:1)];
[α]D22 ϩ39.3 (c 1.467, CHCl3); νmax(neat film)/cmϪ1 3440, 2900,
1605, 1480, 1250, 1210, 1110, 1065, 1015, 756 and 702;
δH(CDCl3) 2.87 (2H, d, J 2.3, OH), 3.56 (2H, dd, J 8.9 and 9.8,
OCH2), 3.70 (2H, dd, J 3.1 and 9.8, OCH2), 3.71 (3H, s,
OCH3), 3.78 (3H, s, OCH3), 4.63 (4H, s, benzylic CH2), 4.94
(2H, ddd, J 2.3, 3.1 and 8.9, CHPh), 6.89 [2H, s, (MeO)2ArH]
(5R,8S,10S,13R)-19,21-Dimethoxy-8,10-dimethyl-5,13-
diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]henicosane-
1(21),17,19-triene 17
By a procedure similar to that described for the preparation of
(S,S,S,S)-16, reaction of (R,R)-15 (3.22 g, 7.35 mmol) with
(S,S)-10 (3.62 g, 8.17 mmol) followed by silica gel chrom-
atography of the products gave (R,S,S,R)-17 (1.70 g, 43%)
[hexane–ethyl acetate (4:1)] as a colourless viscous oil; [α]D24
ϩ133 (c 0.489, CHCl3); νmax(neat film)/cmϪ1 2890, 2850, 1600,
1482, 1452, 1362, 1250, 1222, 1090, 1000, 760 and 700;
δH(CDCl3) 0.91 (6H, d, J 6.3, CH3), 3.10 (2H, dd, J 6.6 and 9.6,
OCH2), 3.22 (2H, dd, J 5.4 and 9.6, OCH2), 3.61–3.67 (6H, m,
OCH2 and CHMe), 3.83 (3H, s, OCH3), 4.05 (3H, s, OCH3),
4.49 (2H, dd, J 4.5 and 11.0 CHPh), 4.50 (2H, d, J 10.9,
benzylic CH2), 4.69 (2H, d, J 10.9, benzylic CH2), 6.90 [2H, s,
(MeO)2ArH] and 7.28–7.34 (10H, m, C6H5) (Found: Mϩ,
536.2817. C32H40O7 requires M, 536.2774).
(S,S,S,S)-21-Hydroxy-19-methoxy-8,10-dimethyl-5,13-diphenyl-
3,6,9,12,15-pentaoxabicyclo[15.3.1]henicosane-1(21),17,19-
triene 18
Ethanethiol (1.18 g, 19.0 mmol) was added slowly to a suspen-
sion of sodium hydride (482 mg, 20.1 mmol) in dry DMF (16
J. Chem. Soc., Perkin Trans. 1, 1997
3233

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cm3) at 0–5 ЊC after which a solution of (S,S,S,S)-16 (535 mg,
0.997 mmol) in dry DMF (15 cm3) was added dropwise to the
resulting clear solution of sodium ethanethiolate in dry DMF
with ice-cooling. The mixture was heated at 100 ЊC for 2 h, and
then cooled to 0–5 ЊC, neutralized with hydrochloric acid and
extracted with ethyl acetate. The combined extracts were
washed with water, dried (MgSO4) and evaporated under
reduced pressure. Chromatography of the residue on silica gel
gave (S,S,S,S)-18 (418 mg, 80%) [hexane–ethyl acetate (3:1)] as
a colourless viscous oil; [α]D22 ϩ133 (c 0.489, CHCl3); νmax(neat
film)/cmϪ1 3350, 2902, 2850, 1600, 1482, 1455, 1370, 1258, 1220,
1120, 1100, 1055, 760 and 702; δH(CDCl3) 1.10 (6H, d, J 6.7,
CH3), 3.25–3.45 (4H, m, OCH2), 3.65–3.78 (4H, m, OCH2),
3.74 (3H, s, OCH3), 4.40–4.45 (2H, m, CHMe), 4.60 (2H, dd,
J 3.5 and 8.7 (CHPh), 4.65 (2H, d, J 10.1, benzylic CH2), 4.76
(2H, d, J 10.1, benzylic CH2), 6.74 (2H, s, HOArH), 7.27–7.38
(10H, m, C6H5) and 7.93 (1H, s, OH) (Found: Mϩ, 522.2595.
C31H38O7 requires M, 522.2618).
tography [hexane–ethyl acetate (2:1)]. Treatment of (R,S,S,R)-
21 with methanol (50 cm3) and a few drops of hydrochloric acid
gave (R,S,S,R)-23 (874 mg, 21%) after silica gel chromato-
graphy [hexane–ethyl acetate (4:1)]; [α]D25 Ϫ59.6 (c 0.286,
CHCl3); νmax(neat film)/cmϪ1 3400, 2900, 1455, 1380, 1338,
1120, 910, 762 and 705; δH(CDCl3) 1.18 (6H, d, J 6.4, CH3),
3.42–3.53 (4H, m, OCH2), 3.62 (2H, dd, J 3.5 and 10.4, OCH2),
3.71 (2H, dd, J 3.0 and 10.4, OCH2), 3.77–3.89 (2H, m, CHMe),
4.13 (2H, br s, OH), 4.85–4.95 (2H, m, CHPh) and 7.22–7.39
(10H, m, C6H5); the high-resolution mass spectrum could not
be recorded because of the weak molecular ion peak; m/z (EI)
(relative intensity) 375 (Mϩ ϩ H, 26), 255 (38), 237 (110) and
117 (34).
(4S,8S,10S,14S)-19,21-Dimethoxy-8,10-dimethyl-4,14-diphenyl-
3,6,9,12,15-pentaoxabicyclo[15.3.1]henicosane-1(21),17,19-
triene 24
A solution of (S,S,S,S)-22 (1.51 g, 4.02 mmol) and 1,3-bis-
(bromomethyl)-2,5-dimethoxybenzene (1.37 g, 4.23 mmol) in
dry THF (430 cm3) was added to a mixture of sodium hydride
(298 mg, 12.4 mmol) and potassium tetrafluoroboranuide (290
mg, 2.29 mmol) in dry THF (170 cm3) over a 15 h period at
50 ЊC, after which the mixture was refluxed for further 48 h.
After the reaction mixture had been cooled to room temper-
ature, it was treated with a small amount of water added
carefully and then concentrated under reduced pressure. The
residue was extracted with ethyl acetate and the combined
extracts were washed with water, dried (MgSO4) and evapor-
ated under reduced pressure. Silica gel chromatography of the
residue gave (S,S,S,S)-24 (774 mg, 36%) [hexane–ethyl acetate
(4:1)] as a colourless viscous oil; [α]D24 ϩ113 (c 0.671, CHCl3);
νmax(neat film)/cmϪ1 2860, 1605, 1490, 1460, 1225, 1100, 1018,
765 and 710; δH(CDCl3), 1.01 (6H, d, J 6.4, CH3), 3.29–3.79
(10H, m, OCH2 and CHMe), 3.77 (3H, s, OCH3), 4.11 (3H, s,
OCH3), 4.27 (2H, d, J 10.0, benzylic CH2), 4.67 (2H, dd, J 2.5
and 9.4 CHPh), 4.68 (2H, d, J 10.0, benzylic CH2), 6.73 [2H, s,
(MeO)2ArH] and 7.30–7.43 (10H, m, C6H5) (Found: Mϩ,
536.2747. C32H40O7 requires M, 536.2774).
(5R,8S,10S,13R)-21-Hydroxy-19-methoxy-8,10-dimethyl-5,13-
diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]henicosane-1(21),
17,19-triene 19
In a manner similar to that described for the preparation of
(S,S,S,S)-18, treatment of (R,S,S,R)-17 (535 mg, 0.997 mmol)
with sodium ethanethiolate in DMF gave (R,S,S,R)-19 (418
mg, 85%) as a colourless viscous oil after silica gel chrom-
atography [hexane–ethyl acetate (4:1)]; [α]D22 Ϫ183 (c 0.203,
CHCl3); νmax(neat film)/cmϪ1 3460, 2900, 2860, 1600, 1485, 1450,
1370, 1250, 1220, 1100, 1062, 760 and 702; δH(CDCl3) 1.15 (6H,
d, J 6.3, CH3), 3.25 (2H, dd, J 7.4 and 8.7, OCH2), 3.53 (2H, dd,
J 4.3 and 8.7, OCH2), 3.62–3.72 (4H, m, OCH2), 3.75 (3H, s,
OCH3), 4.00–4.06 (2H, m, CHMe), 4.66 (2H, dd, J 4.0 and 7.9,
CHPh), 4.72 (4H, s, benzylic CH2), 6.73 (2H, s, HOArH), 7.24–
7.39 (10H, m, C6H5) and 7.75 (1H, s, OH) (Found: Mϩ,
522.2675. C31H38O7 requires M, 522.2618).
(1S,5S,7S,11S)-5,7-Dimethyl-1,11-diphenyl-3,7,9-trioxa-
undecane-1,11-diol 22
A solution of (S)-11 (11.2 g, 50.4 mmol) in dry THF (70 cm3)
was slowly added to a suspension of sodium hydride (1.90 g,
79.2 mmol) in dry THF (40 cm3) after which the mixture was
refluxed for 1.5 h and then treated with a solution of (S,S)-10
(11.0 g, 24.8 mmol) in dry THF (70 cm3) added at room tem-
perature. After the mixture had been refluxed for 30 h, it was
cooled to 0–5 ЊC and treated with a small amount of water,
added carefully. After evaporation of the mixture under
reduced pressure, the residue was extracted with ethyl acetate
and the combined extracts were washed with water, dried
(MgSO4) and evaporated under reduced pressure. Silica gel
chromatography of the residue gave (S,S,S,S)-20 [hexane–ethyl
acetate (9:1)], which was dissolved in methanol (100 cm3) con-
taining a few drops of hydrochloric acid. The solution was
stirred for 12 h at room temperature after which it was evapor-
ated under reduced pressure. The residue was extracted with
ethyl acetate and the combined extracts were washed with aq.
sodium hydrogen carbonate and water, dried (MgSO4) and
evaporated under reduced pressure. Silica gel chromatography
of the residue gave (S,S,S,S)-22 (2.73 g, 28%) [hexane–ethyl
acetate (4:1)]; [α]D25 ϩ94.0 (c 0.792, CHCl3); νmax(neat film)/cmϪ1
3350, 2950, 2900, 1438, 1180, 1062, 995, 960, 748 and 685;
δH(CDCl3) 1.20 (6H, d, J 6.4, CH3), 3.46–3.68 (8H, m, OCH2),
3.76–3.89 (2H, m, CHMe), 4.13 (2H, br s, OH), 4.93 (2H, dd,
J 2.6 and 8.9, CHPh) and 7.22–7.64 (10, m, C6H5) (Found: C,
70.48; H, 8.1. C22H30O5 requires C, 70.56; H, 8.07%).
(4R,8S,10S,14R)-19,21-Dimethoxy-8,10-dimethyl-4,14-
diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]henicosane-1(21),
17,19-triene 25
In a manner similar to that described for the preparation of
(S,S,S,S)-24, reaction of (R,S,S,R)-23 (784 mg, 2.09 mmol)
with 1,3-bis(bromomethyl)-2,5-dimethoxybenzene (737 mg,
2.27 mmol) followed by silica gel chromatography of the prod-
ucts gave (R,S,S,R)-25 (450 mg, 40%) [hexane–ethyl acetate
(4:1)] as a colourless viscous oil; [α]D24 ϩ150 (c 0.453, CHCl3);
νmax(neat film)/cmϪ1 2900, 1610, 1490, 1460, 1245, 1100, 1018,
762 and 705; δH(CDCl3) 1.00 (6H, d, J 6.3, CH3), 3.22–3.59
(8H, m, OCH2), 3.74–4.59 (2H, m, CHMe), 3.79 (3H, s, OCH3),
4.14 (3H, s, OCH3), 4.24 (2H, d, J 10.9, benzylic CH2), 4.61–
4.69 (4H, m, CHPh and benzylic CH2), 6.75 [2H, s, (MeO)2-
ArH] and 7.37–7.43 (10H, m, C6H5); the high-resolution mass
spectrum could not be recorded because of the weak molecular
ion peak; m/z (EI) (relative intensity) 536 (Mϩ, 36), 417 (28),
297 (100), 237 (26), 181 (34) and 165 (26).
(4S,8S,10S,14S)-21-Hydroxy-19-methoxy-8,10-dimethyl-4,14-
diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]henicosane-1(21),
17,19-triene 26
In a manner similar to that described for the preparation of
(S,S,S,S)-18, treatment of (S,S,S,S)-24 (561 mg, 1.05 mmol)
with sodium ethanethiolate in DMF gave (S,S,S,S)-26 (373 mg,
68%) as a colourless viscous oil after silica gel chromatography
[hexane–ethyl acetate (3:1)]; [α]D22 ϩ75.1 (c 0.599, CHCl3);
νmax(neat film)/cmϪ1 3350, 2900, 1590, 1470, 1440, 1335, 1242,
1080, 1015, 745 and 690; δH(CDCl3) 1.19 (6H, d, J 6.7, CH3),
3.35–3.76 (8H, m, OCH2), 3.69 (3H, s, OCH3), 4.23–4.30 (2H,
m, CHMe), 4.50 (2H, d, J 10.9, benzylic CH2), 4.60 (2H, d,
(1R,5S,7S,11R)-5,7-Dimethyl-1,11-diphenyl-3,7,9-trioxa-
undecane-1,11-diol 23
In a manner similar to that described for the preparation of
(S,S,S,S)-22, reaction of (R)-11 (4.89 g, 22.0 mmol) with (S,S)-
10 (4.81 g, 10.9 mmol) gave (R,S,S,R)-21 after silica gel chroma-
3234
J. Chem. Soc., Perkin Trans. 1, 1997

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J 10.9, benzylic CH2), 4.74 (2H, dd, J 3.0 and 9.6, CHPh), 6.59
(2H, s, HOArH), 7.33–7.41 (10H, m, C6H5) and 7.96 (1H, s,
OH) (Found: Mϩ, 522.2597. C31H38O7 requires M, 522.2618).
with CAN (2.49 g, 4.53 mmol) in acetonitrile gave the quinone
derivative (692 mg, 84%) as a yellow oil after silica gel chrom-
atography (chloroform); δH(CDCl3) 1.02 (6H, d, J 6.4, CH3),
3.14 (2H, dd, J 5.9 and 9.4, OCH2), 3.26 (2H, dd, J 5.9 and 9.4,
OCH2), 3.57–3.67 (4H, m, OCH2 and CHMe), 3.72 (2H, dd, J
8.4 and 11.7, OCH2), 4.52 (2H, d, J 14.8 benzylic CH2), 4.54
(2H, dd, J 2.5 and 8.4, CHPh), 4.67 (2H, d, J 14.8 benzylic
CH2), 6.79 (2H, s, the quinone moiety CH) and 7.28–7.38 (10H,
m, C6H5). Treatment of the quinone derivative (690 mg, 1.36
mmol) with 2,4-dinitrophenylhydrazine (1.01 g, 5.12 mmol)
gave (R,S,S,R)-2 (788 mg, 84%) as a red amorphous solid after
silica gel column chromatography [hexane–ethyl acetate (2:1)]
(4R,8S,10S,14R)-21-Hydroxy-19-methoxy-8,10-dimethyl-4,14-
diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]henicosane-1(21),
17,19-triene 27
In a manner similar to that described for the preparation of
(S,S,S,S)-18, treatment of (R,S,S,R)-25 (437 mg, 0.814 mmol)
with sodium ethanethiolate gave (R,S,S,R)-27 (281 mg, 66%) as
a colourless viscous oil after silica gel chromatography [hexane–
ethyl acetate (3:1)]; [α]D22 Ϫ108 (c 0.161, CHCl3); νmax(neat film)/
cmϪ1 3400, 2900, 1605, 1480, 1450, 1240, 1090, 762 and 705;
δH(CDCl3) 1.17 (6H, d, J 6.3, CH3), 3.41–3.73 (8H, m, OCH2),
3.69 (3H, s, OCH3), 4.04–4.16 (2H, m, CHMe), 4.57 (2H, d,
J 11.2, benzylic CH2), 4.64 (2H, d, J 11.2, benzylic CH2), 4.69
(2H, dd, J 2.8 and 10.1, CHPh), 6.59 (2H, s, HOArH), 7.32–
7.40 (10H, m, C6H5) and 7.68 (1H, s, OH); the high-resolution
mass spectrum could not be recorded because of the weak
molecular ion peak; mz (EI) (relative intensity) 522 (Mϩ, 7), 503
(7), 403 (100), 373 (15), 283 (35), 253 (37), 237 (17), 165 (35) and
151 (27).
followed by preparative recycling HPLC (chloroform); λmax
-
(CHCl3)/nm 400 (ε 2.46 × 104); νmax(KBr)/cmϪ1 3250, 2850,
1590, 1530, 1460, 1338, 1290, 1125, 900, 830 and 700;
δH(CDCl3), 1.16 (6H, d, J 6.3, CH3), 3.28 (2H, dd, J 7.3 and 8.9,
OCH2CHMe), 3.54 (2H, dd, J 4.0 and 8.9, OCH2CHMe), 3.70
(2H, dd, J 8.9 and 11.2, OCH2CHPh), 3.77 (2H, dd, J 3.0 and
11.2, OCH2CHPh), 4.00–4.70 (2H, m, CHMe), 4.68 (2H, dd
J 3.0 and 8.9 CHPh), 4.82 (2H, d, J 10.6, benzylic CH2), 4.87
(2H, d J 10.6, benzylic CH2), 7.29–7.41 (10H, m, C6H5), 7.81
[1H, d, J 8.9, (NO2)2ArH], 7.84 (2H, s, HOArH), 8.48 [1H, dd,
J 2.5 and 8.9, (NO2)2ArH], 8.75 [1H, d, J 2.5, (NO2)2ArH] and
9.53 (1H, s, OH) (Found: C, 62.63; H, 5.6; N, 8.21. C36H38O10N4
requires C, 62.97; H, 5.58; N, 8.16%).
(5S,8S,10S,13S)-19-(2Ј,4Ј-Dinitrophenylazo)-21-hydroxy-8,10-
dimethyl-5,13-diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]-
henicosane-1(21),17,19-triene 1
A solution of (S,S,S,S)-18 (317 mg, 0.607 mmol) in acetonitrile
(30 cm3) was added to a solution of CAN (1.03 g, 1.87 mmol) in
acetonitrile (12 cm3). The mixture was stirred for 2 h at room
temperature and then cooled to 0–5 ЊC, when it was treated with
water and extracted with ethyl acetate. The combined extracts
were washed with water, dried (MgSO4) and evaporated under
reduced pressure. The residue was chromatographed on silica
gel to give the quinone derivative (279 mg, 91%) (chloroform)
as a yellow oil; δH(CDCl3) 1.04 (6H, d, J 6.3, CH3), 3.10 (2H,
dd, J 2.5 and 9.7, OCH2), 3.28 (2H, dd, J 9.4 and 9.7, OCH2),
3.72 (2H, dd, J 8.9 and 11.9, OCH2), 3.75 (2H, dd, J 2.0 and
11.9, OCH2), 3.81–3.87 (2H, m, CHMe), 4.35 (2H, d, J 15.2
benzylic CH2), 4.45 (2H, dd, J 2.0 and 8.9, CHPh), 4.38 (2H, d,
J 15.2 benzylic CH2), 6.79 (2H, s, the quinone moiety CH) and
7.28–7.37 (10H, m, C6H5). To a solution of the quinone deriv-
ative (275 mg, 0.543 mmol) in a mixture of methylene dichlor-
ide (12 cm3) and ethanol (12 cm3) was added a solution of 2,4-
dinitrophenylhydrazine (545 mg, 2.75 mmol) in a mixture of
ethanol (12 cm3) and conc. H2SO4 (2 cm3). The mixture was
stirred for 1.5 h at room temperature after which it was diluted
with water and extracted with chloroform. The combined
extracts were washed with aq. sodium hydrogen carbonate and
water, dried (MgSO4) and evaporated under reduced pressure.
The residue was chromatographed on silica gel to give a solid
[hexane–ethyl acetate (2:1)], which was further purified by
preparative recycling HPLC (JAIGEL 1H and JAIGEL 2H
column, chloroform) to give (S,S,S,S)-1 (308 mg, 81%) as a
red amorphous solid; λmax(CHCl3)/nm 405 (ε 2.34 × 104);
νmax(KBr)/cmϪ1 3250, 2860, 1600, 1535, 1348, 1295, 1130, 1115,
905, 830, 760 and 700; δH(CDCl3) 1.12 (6H, d, J 6.6, CH3), 3.27
(2H, dd, J 2.5 and 10.3, OCH2CHMe), 3.46 (2H, dd, J 9.1 and
9.5, OCH2CHPh), 3.70 (2H, t, J 10.3, OCH2CHMe), 3.84 (2H,
dd, J 2.6 and 9.5, OCH2CHPh), 4.11–4.50 (2H, m, CHMe),
4.60 (2H, dd, J 2.5 and 9.1 CHPh), 4.78 (2H, d, J 11.1, benzylic
CH2), 4.88 (2H, d, J 11.1, benzylic CH2), 7.28–7.37 (10H, m,
C6H5), 7.83 [1H, d, J 8.9, (NO2)2ArH], 7.85 (2H, s, HOArH),
8.49 [1H, dd, J 2.3 and 8.9, (NO2)2ArH], 8.75 [1H, d, J 2.3,
(NO2)2ArH] and 9.45 (1H, s, OH) (Found: C, 62.64; H, 5.6; N,
8.22. C36H38O10N4 requires C, 62.97; H, 5.58; N, 8.16%).
(4S,8S,10S,14S)-19-(2Ј,4Ј-Dinitrophenylazo)-21-hydroxy-8,10-
dimethyl-4,14-diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]-
henicosane-1(21),17,19-triene 3
By a procedure similar to that described for the preparation of
(S,S,S,S)-1, oxidation of (S,S,S,S)-26 (317 mg, 0.607 mmol)
with CAN (1.03 g, 1.87 mmol) in acetonitrile followed by silica
gel chromatography of the products gave the quinone derivative
(289 mg, 94%) (chloroform) as a yellow oil; δH(CDCl3) 1.10
(6H, d, J 6.3, CH3), 3.27–3.61 (8H, m, OCH2), 3.76–3.83 (2H,
m, CHMe), 4.30 (2H, d, J 15.2 benzylic CH2), 4.64 (2H,
dd, J 4.0 and 7.9, CHPh), 4.79 (2H, d, J 15.2 benzylic CH2),
6.76 (2H, s, the quinone moiety CH) and 7.29–7.42 (10H, m,
C6H5). Treatment of the quinone derivative (279 mg, 0.551
mmol) with 2,4-dinitrophenylhydrazine (861 mg, 4.35 mmol)
gave (S,S,S,S)-3 (487 mg, 81%) as a red amorphous solid after
silica gel column chromatography [hexane–ethyl acetate (2:1)]
followed by preparative recycling HPLC (chloroform);
λmax(CHCl3)/nm 406 (ε 2.38 × 104); νmax(KBr)/cmϪ1 3250, 2850,
1590, 1535, 1345, 1290, 1110, 1030, 900, 835, 758 and 700;
δH(CDCl3) 1.22 (6H, d, J 6.6, CH3), 3.40 (2H, dd, J 4.5 and 9.6,
OCH2CHMe), 3.55 (2H, dd, J 2.7 and 10.9, OCH2CHPh), 3.69
(2H, t, J 9.6, OCH2CHMe), 3.71 (2H, dd, J 5.8 and 10.9,
OCH2CHPh), 4.28–4.39 (2H, m, CHMe), 4.61 (2H, dd, J 2.7
and 10.9 CHPh), 4.61 (2H, d, J 11.1, benzylic CH2), 4.71 (2H,
d, J 11.1, benzylic CH2), 7.34–7.47 (10H, m, C6H5), 7.78 [1H, d,
J 8.9, (NO2)2ArH], 7.71 (2H, s, HOArH), 8.46 [1H, dd, J 2.5,
8.9, (NO2)2ArH], 8.73 [1H, d, J 2.5, (NO2)2ArH] and 9.53 (1H,
s, OH) (Found: C, 62.79; H, 5.5; N, 8.05. C36H38O10N4 requires
C, 62.97; H, 5.58; N, 8.16%).
(4R,8S,10S,14R)-19-(2Ј,4Ј-Dinitrophenylazo)-21-hydroxy-8,10-
dimethyl-4,14-diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]-
henicosane-1(21),17,19-triene 4
By a procedure similar to that described for the preparation of
(S,S,S,S)-1, oxidation of (R,S,S,R)-27 (279 mg, 0.534 mmol)
with CAN (888 mg, 1.62 mmol) in acetonitrile gave the quinone
derivative (228 mg, 84%) as a yellow oil after silica gel chrom-
atography (chloroform); δH(CDCl3) 1.10 (6H, d, J 6.2, CH3),
3.28 (2H, dd, J 4.6 and 9.3, OCH2), 3.43 (2H, dd, J 6.3 and 9.3,
OCH2), 3.49–3.63 (4H, m, OCH2), 3.67–3.74 (2H, m, CHMe),
4.42 (2H, d, J 15.2 benzylic CH2), 4.66 (2H, dd, J 2.7 and 8.9,
CHPh), 4.73 (2H, d, J 14.8 benzylic CH2), 6.75 (2H, s, the
quinone moiety CH) and 7.31–7.38 (10H, m, C6H5). Treatment
of the quinone derivative (220 mg, 0.436 mmol) with 2,4-
(5R,8S,10S,13R)-19-(2Ј,4Ј-Dinitrophenylazo)-21-hydroxy-8,10-
dimethyl-5,13-diphenyl-3,6,9,12,15-pentaoxabicyclo[15.3.1]-
henicosane-1(21),17,19-triene 2
By a procedure similar to that described for the preparation of
(S,S,S,S)-1, oxidation of (R,S,S,R)-19 (776 mg, 1.48 mmol)
J. Chem. Soc., Perkin Trans. 1, 1997
3235

View Article Online
H. Chikamatsu, Bull. Chem. Soc. Jpn., 1989, 62, 83; K. Naemura,
dinitrophenylhydrazine (431 mg, 2.18 mmol) gave (R,S,S,R)-4
(246 mg, 81%) as a red amorphous solid after silica gel column
chromatography [hexane–ethyl acetate (2:1)] followed by pre-
parative recycling HPLC (chloroform); λmax(CHCl3)/nm 404 (ε
2.23 × 104); νmax(KBr)/cmϪ1 3250, 2900, 1598, 1530, 1460, 1340,
1285, 1125, 1110, 905, 830, 760 and 700; δH(CDCl3) 1.12 (6H, d,
J 6.4, CH3), 3.46 (2H, dd, J 4.9 and 9.2, OCH2CHMe), 3.58–
3.77 (6H, m, OCH2), 4.07–4.11 (2H, m, CHMe), 4.73–4.76 (6H,
m, CHPh and benzylic CH2), 7.33–7.42 (10H, m, C6H5), 7.72
(2H, s, HOArH), 7.79 [1H, d, J 8.9, (NO2)2ArH], 8.47 [1H, dd,
J 2.5, 8.9, (NO2)2ArH], 8.74 [1H, d, J 2.5, (NO2)2ArH] and 9.53
(1H, s, OH) (Found: C, 62.74; H, 5.6; N, 8.07. C36H38O10N4
requires C, 62.97; H, 5.58; N, 8.16%).
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References
1 A preliminary communication of part of this work has appeared:
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Paper 7/03452K
Received 19th May 1997
Accepted 5th August 1997
3236
J. Chem. Soc., Perkin Trans. 1, 1997