Synthesis and enantiodifferentiating properties of chiral aza crown ethers

Article abstract of DOI:10.1023/B:RUJO.0000003200.41968.46

Alkylation of 2-substituted (4S,5S)-4,5-bis(hydroxymethyl)-1,3-dioxolanes with 9-benzyl-1,17-diiodo-3,6,12,15-tetraoxa-9-azaheptadecane afforded new chiral aza and diaza crown ethers as a result of [1 + 1] and [2 + 2] additions. Their catalytic debenzylat

Full text of DOI:10.1023/B:RUJO.0000003200.41968.46

Russian Journal of Organic Chemistry, Vol. 39, No. 7, 2003, pp. 1037 1041. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 7, 2003,
pp. 1101 1106.
Original Russian Text Copyright
2003 by Lobach, Leus, Titova, Luk’yanenko.
Synthesis and Enantiodifferentiating Properties
of Chiral Aza Crown Ethers
A. V. Lobach, O. N. Leus, N. Yu. Titova, and N. G. Luk’yanenko
Bogatskii Physicochemical Institute, Ukrainian National Academy of Sciences,
Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine
e-mail: ngl@farlep.net
Received June 17, 2002
Abstract Alkylation of 2-substituted (4S,5S)-4,5-bis(hydroxymethyl)-1,3-dioxolanes with 9-benzyl-1,17-di-
iodo-3,6,12,15-tetraoxa-9-azaheptadecane afforded new chiral aza and diaza crown ethers as a result of [1+1]
and [2+2] additions. Their catalytic debenzylation gave the corresponding derivatives with a secondary amino
group. The reaction of diethyl (+)-tartrate and diethyl (4S,5S)-1,3-dioxolane-4,5-diacetates with 1,8-diamino-
3,6-dioxaoctane led to formation of chiral macrocyclic lactams which were reduced with lithium aluminum
hydride. The resulting diaza crown ethers were tested for enantioselectivity in complex formation with L- and
D-valine methyl ester by the potentiometric method. In most cases, the aza crown ethers showed better
enantioselectivity than their oxygen analogs.
Chiral crown ethers are among the most efficient
enantiodifferentiating receptors for amines, amino
acids, and their derivatives [1]. Therefore, they can
be used as catalysts in asymmetric reactions, enantio-
selective sensors, enantiodifferentiating agents, and
models of biological systems [2, 3]. Effective enantio-
meric recognition requires that a chiral macrocyclic
receptor be capable of forming sufficiently stable
complexes with substrate enantiomers and that a chiral
barrier be present, which reduces the stability of one
of the diastereoisomeric complexes thus formed [3].
In other words, enantiodifferentiating properties of
chiral crown ethers are determined by the satbility of
complexes with chiral substrates and by the nature
of chiral fragment in the macroring.
crown ethers and enantioselectivity of their reaction
with L- and D-valine methyl esters [6]. In continuation
of these studies we now report on the synthesis and
enantiodifferentiating properties of new chiral aza and
diaza crown ethers.
As starting compounds we used chiral substituted
1,3-dioxolanes Ia and Ib. Their condensation with
9-benzyl-1,17-diiodo-3,6,12,15-tetraoxa-9-azahepta-
decane in dioxane in the presence of sodium hydride
gave previously unknown N-benzyl-substituted aza
(IIa, IIb) and diaza crown ethers (IIIa, IIIb) which
can be regarded, respectively, as [1+1] and [2+2]
condensation products. Catalytic hydrogenation of
compounds IIa, IIb, IIIa, and IIIb afforded aza
crown ethers IIc and IId and diaza crown ethers IIIc
and IIId (Scheme 1).
We have proposed a convenient procedure for the
preparation of chiral amides V, VIa, and VIb by
reaction of diethyl (+)-tartrate or 1,3-dioxolanes IVa
and IVb with 1,8-diamino-3,6-dioxaoctane in methyl
alcohol in the presence of sodium methoxide. The
subsequent reduction of lactams V, VIa, and VIb
with lithium aluminum hydride in tetrahydrofuran
gave diaza crown ethers VII, VIIIa, and VIIIb,
respectively (Scheme 2).
Complexing power of chiral crown ethers depends
on a number of factors, including the nature of donor
groups in the macroring. In many cases, introduction
of nitrogen atoms into the macrocyclic skeleton
increases the stability of complexes with ammonium
ion and amine and amino acid salts [4]. However,
among a large series of chiral crown ethers, aza crown
ethers have been studied to the least extent [1]. As far
as we know, only our early publication [5] described
the synthesis and enantiomeric selectivity of several
chiral aza crown ethers on the basis of natural (+)-tar-
taric acid derivatives. In the preceding communication
we reported on the synthesis of a series of chiral
The enantioselectivity of complex formation of
aza crown ethers IIa IId, IIIa IIId, V, VIa, VIb,
VII, VIIIa, and VIIIb with L- and D-valine methyl
1070-4280/03/3907-1037$25.00 2003 MAIK Nauka/Interperiodica

1038
LOBACH et al.
Scheme 1.
I, R1 = Me, R2 = t-Bu (a); R1 = H, R2 = Ph (b); II, R1 = Me, R2 = t-Bu, R3 = Bzl (a); R1 = H, R2 = Ph, R3 = Bzl (b); R1 = Me,
R2 = t-Bu, R3 = H (c); R1 = R3 = H, R2 = Ph (d); III, R1 = Me, R2 = t-Bu, R3 = Bzl (a); R1 = H, R2 = Ph, R3 = Bzl (b); R1 = Me,
R2 = t-Bu, R3 = H (c); R1 = R3 = H, R2 = Ph (d).
ester hydrochlorides was estimated by the potentio-
metric enantioselectivity coefficients KLD [7]. The
KLD values (averaged from 5 7 measurements) are
given in table. These coefficients characterize pre-
ference of complex formation between aza crown
ether and one enantiomer of the substrate: when KLD
is equal to unity, enantioselectivity in complex forma-
tion is absent; KLD values larger or lesser than unity
indicate predominant complex formation of aza crown
ether with L- or D-valine methyl ester, respectively.
All the examined aza crown ethers reacted pre-
ferentially with L-valine methyl ester hydrochloride,
and their enantioselectivity was considerably higher
than that of the oxygen analogs [6] (except for amides
V, VIa and VIb). Presumably, increased enantioselec-
tivity in the complex formation with chiral aza crown
ethers is explained by greater stability of complexes
with amino acid esters, as compared to similar com-
plexes derived from nitrogen-free crown ethers. Aza
crown ethers IIc, IId, IIIc, and IIId are characterized
Scheme 2.
IV, VI, VIII, R1 = Me, R2 = t-Bu (a); R1 = H, R2 = Ph (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 7 2003

SYNTHESIS AND ENANTIODIFFERENTIATING PROPERTIES
1039
by higher KLD values (1.82 1.98) than their N-benzyl
derivatives IIa, IIb, IIIa, IIIb (KLD 1.55 1.73). This
may be due to additional stabilization of the com-
plexes via hydrogen bonding. The maximal enantio-
selectivity was observed for diaza crown ethers VIIIa
and VIIIb (KLD 2.07 and 2.12, respectively).
On the whole, our results indicate that search for
new ligands exhibiting high enantioselectivity is more
promising in the series of aza crown ethers containing
(+)-tartaric acid moieties.
Enantioselectivity coefficients of aza crown ethers IIa IId,
IIIa IIId, V, VIa, VIb, VII, VIIIa, and VIIIb
Compound no.
KLD
Compound no.
KLD
IIa
IIb
IIc
IId
IIIa
IIIb
IIIc
1.68
1.73
1.92
1.98
1.55
1.58
1.82
IIId
V
VIa
VIb
VII
1.86
1.28
1.38
1.35
1.64
2.07
2.12
VIIIa
VIIIb
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
7.10 7.19 m (5H, Ph). Found, %: C 55.97; H 7.80;
N 3.31; Cl 17.44. C19H31Cl2NO4. Calculated, %:
C 55.88; H 7.65; N 3.43; Cl 17.36.
AM-250 instrument (250 MHz) in DMSO-d6 using
TMS as internal reference. The molecular weights
were determined from the mass spectra which were
obtained on Varian MAT-112 and MKh-1321 mass
spectrometers with direct sample admission into the
ion source (energy of ionizing electrons 70 eV). The
optical rotations ([ ]2D0) were measured on a Perkin
Elmer 241 MC polarimeter. GLC analysis was per-
formed on a Chrom-5 chromatograph equipped with
a flame-ionization detector; glass column, 1200
3 mm; stationary phase SE-30 (5%) on Inerton AW-
DMCS (0.100 0.125 mm); carrier gas helium. Glass
plates with a fixed layer of neutral aluminum oxide
(L 5/40 m) were used for TLC; eluent chloroform
benzene methanol 2-propanol, 8:3:0.3:0.3; develop-
ment with iodine vapor; also, Silufol plates were used
(eluent chloroform methanol acetone, 2:1:1; deve-
lopment with a solution of ninhydrin in diethyl ether).
Preparative liquid chromatography was performed in
glass columns charged with neutral aluminum oxide
(L 40/250 m; eluent chloroform benzene methanol
2-propanol, 8:3:0.3:0.3) or silica gel (L 40/100 m;
eluent chloroform methanol acetone, 2:1:1). Com-
pounds Ia, Ib, IVa, and IVb [6] and 1,8-diamino-3,6-
dioxaoctane [8] were prepared by known methods.
A solution of 6.5 g (16 mmol) of 9-benzyl-1,17-di-
chloro-3,6,12,15-tetraoxa-9-azaheptadecane and 7.2 g
(48 mmol) of sodium iodide in 15 ml of anhydrous
acetonitrile was heated for 14 h under reflux with
vigorous stirring. The mixture was cooled and filtered,
the precipitate was washed with two 10-ml portions
of acetonitrile, and the solvent was distilled off under
reduced pressure. The residue was dissolved in 15 ml
of diethyl ether, the solution was filtered, and the
filtrate was evaporated to obtain 9.1 g (97%) of 9-ben-
zyl-1,17-diiodo-3,6,12,15-tetraoxa-9-azaheptadecane
1
as a light yellow oily liquid. H NMR spectrum, ,
ppm: 2.65 t (4H, NCH2), 3.05 q (4H, OCH2), 3.44
3.64 m (18H, OCH2, CH2Ph), 7.05 7.11 m (5H, Ph).
Found, %: C 38.72; H 5.34; I 42.76; N 2.42.
C19H31I2NO4. Calculated, %: C 38.60; H 5.29;
I 42.93; N 2.37.
Aza crown ethers IIa, IIb, IIIa, and IIIb. A solu-
tion of 2.5 g ( 12 mmol) of 1,3-dioxolane Ia or Ib
in 230 ml of anhydrous dioxane was added dropwise
with stirring under argon to a suspension of 2.9 g
(120 mmol) of sodium hydride in 170 ml of an-
hydrous dioxane. The mixture was stirred for 1 h at
50 60 C, and a solution of 7.1 g (12 mmol) of 9-ben-
zyl-1,17-diiodo-3,6,12,15-tetraoxa-9-azaheptadecane
in 230 ml of anhydrous dioxane was added. The mix-
ture was stirred for 16 h at 70 80 C, cooled, and
poured into 200 ml of ice water. The products were
extracted into chloroform (5 100 ml), the extract was
dried over Na2SO4, and the solvent was distilled off
under reduced pressure. Pure products IIa, IIb, IIIa,
and IIIb were isolated as colorless oily substances by
column chromatography on neutral aluminum oxide.
9-Benzyl-1,17-diiodo-3,6,12,15-tetraoxa-9-aza-
heptadecane. A mixture of 69.2 g (370 mmol) of
1,8-dichloro-3,6-dioxaoctane, 4.9 g (46 mmol) of
benzylamine, and 12.2 g (115 mmol) of sodium car-
bonate was stirred for 8 h at 120 C. The mixture was
cooled, dissolved in 200 ml of methanol, and filtered,
and the precipitate was washed with methanol
(2 20 ml). The filtrate was combined with the
washings and evaporated, and the residue was sub-
jected to column chromatography on neutral Al2O3
to isolate 12.5 g (67%) of 9-benzyl-1,17-dichloro-
3,6,12,15-tetraoxa-9-azaheptadecane as a colorless
(1S,23S)-12-Benzyl-25-(tert-butyl)-25-methyl-
3,6,9,15,18,21,24,26-octaoxa-12-azabicyclo[21.3.0]-
hexacosane (IIa). Yield 3.4 g (52%). [ ]2D0 = 4.2
1
oily liquid. H NMR spectrum, , ppm: 2.59 t (4H,
NCH2), 3.48 3.62 m (22H, OCH2, ClCH2, CH2Ph),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 7 2003

1040
LOBACH et al.
(IIc). Yield 0.53 g (98%). [ ]D20
=
2.2 (c = 1.0,
1
(c = 3.0, CH3OH). H NMR spectrum, , ppm: 0.98 s
(9H, t-Bu), 1.30 s (3H, CH3), 2.66 t (4H, NCH2),
3.52 3.74 m (26H, OCH2, CH2Ph), 3.82 4.06 m (2H,
OCH), 7.07 7.14 m (5H, Ph). Found, %: C 64.61;
H 9.19; N 2.57. M+ 539. C29H49NO8. Calculated, %:
C 64.54; H 9.15; N 2.60. M 539.71.
1
CH3OH). H NMR spectrum, , ppm: 0.98 s (9H,
t-Bu), 1.30 s (3H, CH3), 2.36 br.s (1H, NH), 2.78
2.88 m (4H, NCH2), 3.50 3.62 m (24H, OCH2),
3.80 4.02 m (2H, OCH). Found, %: C 58.84; H 5.60;
N 3.16. M+ 449. C22H43NO8. Calculated, %: C 58.78;
H 5.56; N 3.12. M 449.58.
(1S,23S)-12-Benzyl-25-phenyl-3,6,9,15,18,21,24,-
26-octaoxa-12-azabicyclo[21.3.0]hexacosane (IIb).
(1S,23S)-25-Phenyl-3,6,9,15,18,21,24,26-octaoxa-
12-azabicyclo[21.3.0]hexacosane (IId). Yield 0.52 g
Yield 3.6 g (56%). [ ]2D0 = +8.4 (c = 3.0, CH3OH).
1H NMR spectrum, , ppm: 2.70 t (4H, NCH2), 3.54
3.76 m (26H, OCH2, CH2Ph), 3.90 3.98 m (2H,
OCH), 5.98 s (1H), 7.16 7.42 m (10H, Ph). Found,
%: C 59.95; H 7.88; N 2.61. M+ 545. C30H43NO8.
Calculated, %: C 66.03; H 7.94; N 2.57. M 545.67.
(97%). [ ]2D0 = +6.3 (c = 1.0, CH3OH). H NMR
1
spectrum, , ppm: 2.40 br.s (1H, NH), 2.90 3.04 m
(4H, NCH2), 3.54 3.64 m (24H, OCH2), 3.86 3.92 m
(2H, OCH), 5.98 s (1H), 7.35 7.50 m (5H, Ph).
Found, %: C 60.60; H 8.14; N 3.11. M+ 455.
C23H37NO8. Calculated, %: C 60.64; H 8.19; N 3.08.
M 455.55.
(1S,23S,27S,49S)-12,38-Dibenzyl-25,51-di-tert-
butyl-25,51-dimethyl-3,6,9,15,18,21,24,26,29,32,35,-
41,44,47,50,52-hexadecaoxa-12,38-diazatricyclo-
(1S,23S,27S,49S)-25,51-Di-tert-butyl-25,51-di-
[47.3.0.023,27]dopentacontane (IIIa). Yield 1.3 g
methyl-3,6,9,15,18,21,24,26,29,32,35,41,44,47,50,52-
(10%). [ ]2D0
=
3.8 (c = 3.0, CH3OH). H NMR
1
hexadecaoxa-12,38-diazatricyclo[47.3.0.023,27]do-
pentacontane (IIIc). Yield 1.0 g (93%). [ ]2D0 = +8.1
spectrum, , ppm: 0.98 s (18H, t-Bu), 1.30 s (6H,
CH3), 2.64 t (8H, NCH2), 3.50 3.72 m (52H, OCH2,
CH2Ph), 3.76 3.96 m (4H, OCH), 7.06 7.15 m (10H,
Ph). Found, %: C 64.48; H 9.09; N 2.64. M+ 1078.
C58H98N2O16. Calculated, %: C 64.54; H 9.15;
N 2.60. M 1079.42.
1
(c = 5.0, CH3OH). H NMR spectrum, , ppm: 0.96 s
(18H, t-Bu), 1.31 s (6H, CH3), 2.52 br.s (2H, NH),
2.84 2.96 m (8H, NCH2), 3.52 3.68 m (48H, OCH2),
3.77 3.98 m (4H, OCH). Found, %: C 58.73; H 9.70;
N 3.07. M + 898. C44H86N2O16. Calculated, %:
C 58.78; H 9.64; N 3.12. M 899.17.
(1S,23S,27S,49S)-12,38-Dibenzyl-25,51-diphenyl-
3,6,9,15,18,21,24,26,29,32,35,41,44,47,50,52-hexa-
(1S,23S,27S,49S)-25,51-Diphenyl-3,6,9,15,18,21,-
24,26,29,32,35,41,44,47,50,52-hexadecaoxa-12,38-
decaoxa-12,38-diazatricyclo[47.3.0.023,27]dopenta-
contane (IIIb). Yield 0.91 g (7%). [ ]2D0 = +4.2 (c =
diazatricyclo[47.3.0.023,27]dopentacontane (IIId).
Yield 1.0 g (94%). [ ]2D0 = 14.3 (c = 5.0, CH3OH).
1H NMR spectrum, , ppm: 2.48 br.s (2H, NH), 2.94
3.05 m (8H, NCH2), 3.52 3.66 m (48H, OCH2),
3.89 3.98 m (4H, OCH), 5.98 s (2H), 7.38 7.52 m
(10H, Ph). Found, %: C 60.70; H 8.14; N 3.12.
M+ 910. C46H74N2O16. Calculated, %: C 60.65;
H 8.19; N 3.08. M 911.09.
1
3.0, CH3OH). H NMR spectrum, , ppm: 2.68 t (8H,
NCH2), 3.50 3.62 m (52H, OCH2, CH2Ph), 3.86
3.92 m (4H, OCH), 5.97 s (2H), 7.12 7.46 m (20H,
Ph). Found, %: C 65.98; H 8.00; N 2.61. M+ 1090.
C60H86N2O16. Calculated, %: C 66.04; H 7.94;
N 2.57. M 1091.34.
Aza crown ethers IIc, IId, IIIc, and IIId.
A stream of hydrogen was passed under stirring over
a period of 2 h through a suspension of 100 mg of
palladium black in 20 ml of anhydrous methanol, and
0.65 g ( 1.2 mmol) of aza crown ether IIa or IIb or
1.3 g ( 1.2 mmol) of diaza crown ether IIIa or IIIb
was added. The mixture was stirred while passing
hydrogen for 8 h (compounds IIa and IIb) or 16 h
(IIIa and IIIb). The precipitate was filtered off and
washed with methanol (2 10 ml), the filtrate was
combined with the washings, and the solvent
(methanol and toluene formed during the reaction)
was distilled off on a rotary evaporator. Almost pure
aza crown ethers IIc, IId, IIIc, and IIId were thus
isolated as colorless oily substances.
Aza crown ethers V, VIa, and VIb. Diethyl
(+)-tartrate, 2.1 g (10 mmol), or dioxolane IVa or
IVb, 2.9 g ( 10 mmol), and 1,8-diamino-3,6-dioxa-
octane, 1.5 g (10 mmol), were added to a solution of
0.023 g (1 mmol) of metallic sodium in 200 ml of
anhydrous methanol. The mixture was heated with
stirring for 6 h under reflux in an argon atmosphere,
concentrated, and cooled, and the crude product
(brown crystals) was filtered off. Compounds V, VIa,
and VIb were purified by column chromatography on
silica gel, followed by recrystallization from anhy-
drous ethanol. The products were colorless hygro-
scopic crystalline substances.
(9R,10R)-9,10-Dihydroxy-1,4-dioxa-7,12-diaza-
cyclotetradecane-8,11-dione (V). Yield 0.95 g (35%).
mp 161 162 C. [ ]2D0 = +28.4 (c = 2.5, CH3OH).
(1S,23S)-25-tert-Butyl-25-methyl-3,6,9,15,18,21,-
24,26-octaoxa-12-azabicyclo[21.3.0]hexacosane
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SYNTHESIS AND ENANTIODIFFERENTIATING PROPERTIES
1041
1H NMR spectrum, , ppm: 3.34 3.41 m (4H, NCH2),
3.48 3.60 m (8H, OCH2), 4.12 4.29 m (2H, OCH),
4.82 br.s (2H, OH), 7.52 7.76 m (2H, NH). Found,
%: C 45.87; H 7.02; N 10.74. M+ 262. C10H18N2O6.
Calculated, %: C 45.80; H 6.92; N 10.68. M 262.26.
NCH2), 3.50 3.60 m (8H, OCH2), 3.74 3.96 m (2H,
OCH). Found, %: C 60.68; H 10.25; N 8.88. M+ 316.
C16H32N2O4. Calculated, %: C 60.73; H 10.19;
N 8.85. M 316.44.
(1S,14S)-16-Phenyl-6,9,15,17-tetraoxa-3,12-di-
azabicyclo[12.3.0]heptadecane (VIIIb). Yield 0.47 g
(1R,14R)-16-tert-Butyl-16-methyl-6,9,15,17-tetra-
(72%). [ ]2D0 = 16.3 (c = 1.0, CH3OH). H NMR
1
oxa-3,12-diazabicyclo[12.3.0]heptadecane-2,13-di-
one (VIa). Yield 1.5 g (42%). mp 126 127 C. [ ]D20
=
spectrum, , ppm: 2.41 br.s (2H, NH), 2.87 3.02 m
(8H, NCH2), 3.54 3.65 m (8H, OCH2), 3.90 4.02 m
(2H, OCH), 5.96 s (1H), 7.38 7.52 m (5H, Ph).
Found, %: C 63.29; H 8.06; N 8.74. M+ 322.
C17H26N2O4. Calculated, %: C 63.33; H 8.13; N 8.69.
M 322.40.
Enantioselectivity coefficients of aza crown
ethers IIa IId, IIIa IIId, V, VIa, VIb, VII, VIIIa,
and VIIIb were determined by measuring the mem-
brane potential of an [Ag, AgCl/internal solution//
membrane//working solution/Ag, AgCl] cell by the
biionic potential technique in 0.01 M aqueous solu-
tions of L- and D-valine methyl ester hydrochlorides,
following the procedure described in [6].
+16.5 (c = 2.5, CH3OH). 1H NMR spectrum, , ppm:
0.96 s (9H, t-Bu), 1.31 s (3H, CH3), 3.30 3.40 m (4H,
NCH2), 3.50 3.64 m (8H, OCH2), 4.18 4.62 m (2H,
OCH), 7.17 7.37 m (2H, NH). Found, %: C 55.72;
H 8.21; N 8.07. M+ 344. C16H28N2O6. Calculated, %:
C 55.80; H 8.19; N 8.13. M 344.41.
(1R,14R)-16-Phenyl-6,9,15,17-tetraoxa-3,12-di-
azabicyclo[12.3.0]heptadecane-2,13-dione (VIb).
Yield 1.4 g (40%). mp 142 143 C. [ ]D20
=
10.4
1
(c = 2.5, CH3OH). H NMR spectrum, , ppm: 3.35
3.42 m (4H, NCH2), 3.48 3.60 m (8H, OCH2), 4.56
4.62 m (2H, OCH), 5.97 s (1H), 7.05 7.58 m (7H,
NH, Ph). Found, %: C 58.33; H 6.28; N 7.92. M+ 350.
C17H22N2O6. Calculated, %: C 58.28; H 6.33; N 7.99.
M 350.37.
REFERENCES
Aza crown ethers VII, VIIIa, and VIIIb. Di-
amide V (0.52 g, 2.0 mmol), VIa (0.69 g, 2.0 mmol),
or VIb (0.70 g, 2.0 mmol) was added in small
portions under vigorous stirring in an argon atmos-
phere to a suspension of 0.15 g (4.0 mmol) of lithium
aluminum hydride in 10 ml of anhydrous THF. The
mixture was then stirred for 3 h at room temperature,
heated for 4 h under reflux, and left overnight. Cold
water, 0.15 ml was added, the mixture was filtered,
and the precipitate was shaken with 10 ml of THF and
filtered off. This procedure was repeated thrice. The
filtrates were combined and evaporated under reduced
pressure. The residue was dissolved in benzene, and
the solution was heated under reflux in a flask
equipped with a Dean Stark trap until water was
removed completely. The solvent was distilled off
under reduced pressure to isolate diaza crown ether
VII, VIIIa, or VIIIb as a colorless oily liquid.
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2. Lehn, J.-M., Supramolecular Chemistry: Concepts and
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under the title Supramolekulyarnaya khimiya, Novo-
sibirsk: Nauka, Sib. Predpr. Ross. Akad. Nauk, 1998,
p. 156.
3. Stoddart, J.F., Topics in Stereochemistry, Eliel, E.L.
and Wilen, S.H., Eds., New York: Wiley, 1987,
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(9S,10S)-1,4-Dioxa-7,12-diazacyclotetradecane-
9,10-diol (VII). Yield 0.29 g (64%). [ ]2D0 = +8.0
1
(c = 1.0, CH3OH). H NMR spectrum, , ppm: 2.73
2.84 m (8H, NCH2), 3.11 br.s (4H, NH, OH), 3.50
3.62 m (8H, OCH2), 3.69 3.78 m (2H, OCH). Found,
%: C 51.22; H 9.50; N 12.04. M+ 234. C10H22N2O4.
Calculated, %: C 51.26; H 9.46; N 11.96. M 234.29.
(1S,14S)-16-tert-Butyl-16-methyl-6,9,15,17-tetra-
oxa-3,12-diazabicyclo[12.3.0]heptadecane (VIIIa).
Yield 0.49 g (78%). [ ]2D0 = +22.2 (c = 1.0, CH3OH).
1H NMR spectrum, , ppm: 0.92 s (9H, t-Bu), 1.23 s
(3H, CH3), 2.33 br.s (2H, NH), 2.85 2.97 m (8H,
8. Basok, S.S., Kirichenko, T.I., Shcherbakov, S.V.,
Limich, V.V., and Lobach, A.V., Reaktiv. Osobo
Chist. Veshch-va., 1983, no. 3, p. 51.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 7 2003