Synthesis and monolayer behavior of amphiphilic per(2,3-di-O-alkyl)-α- and β-cyclodextrins and hexakis(6-deoxy-6-thio-2,3-di-O-pentyl)-α-cyclodextrin at an air-water interface

Article abstract of DOI:10.1016/S0040-4039(00)01628-2

A synthesis of amphiphilic per(2,3-di-O-alkyl)-α- and β-cyclodextrins and hexakis(6-deoxy-6-thio-2,3-di-O-pentyl)-α-cyclodextrin and their monolayer behavior on a water surface is presented. Long alkyl chains were introduced by a treatment of the per(6-O-

Full text of DOI:10.1016/S0040-4039(00)01628-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9119–9123
Synthesis and monolayer behavior of amphiphilic
per(2,3-di-O-alkyl)-a- and b-cyclodextrins and
hexakis(6-deoxy-6-thio-2,3-di-O-pentyl)-a-cyclodextrin at an
air–water interface
a
a,
b
a
Monika Wazynska, Andrzej Temeriusz, * Kazimierz Chmurski, Renata Bilewicz and
a,b
Janusz Jurczak
a
Department of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland
b
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 26 July 2000; revised 15 September 2000; accepted 20 September 2000
Abstract
A synthesis of amphiphilic per(2,3-di-O-alkyl)-a- and b-cyclodextrins and hexakis(6-deoxy-6-thio-2,3-
di-O-pentyl)-a-cyclodextrin and their monolayer behavior on a water surface is presented. Long alkyl
chains were introduced by a treatment of the per(6-O-tert-butyldimethylsilyl) derivatives with an
appropriate alkyl iodide in dimethylformamide in the presence of sodium hydride. A standard desilylation
procedure followed by an iodination reaction afforded per(6-deoxy-6-iodo) analogues. In the latter
reaction step, sulphur containing groups were introduced by nucleophilic substitution of the iodine with
benzothiolate ion in dimethylformamide. The hexakis(6-deoxy-6-S-benzyl-2,3-di-O-pentyl)-a-cyclodextrin
was transformed into extremely interesting hexakis(6-deoxy-6-thio-2,3-di-O-pentyl)-a-cyclodextrin. The
surface pressure−mean molecular area (y−A) isotherms indicated that the synthesised amphiphilic
cyclodextrin derivatives were capable of forming stable monolayers at the air–water interface. The shapes
of the isotherms were typical for solid-like monolayers except for hexakis(6-deoxy-6-thio-2,3-di-O-pen-
tyl)cyclomaltohexaoses which formed a more liquid monolayer. © 2000 Elsevier Science Ltd. All rights
reserved.
Keywords: cyclodextrins; synthesis; thio; amphiphilic.
1,2
In continuation of our interest in the synthesis and application of amphiphilic cyclodextrins,
we have designed supramolecular systems which would be capable of acting in a double fashion,
as an amphiphile and as a receptor to anchor on the surface of the electrode. Amphiphilic
cyclodextrins, in general, may be formed in two ways using chemical modifications: hydrophobic
*
Corresponding author. Tel: (0-22)8222325; fax: (0-22)8225996; e-mail: atemer@chem.uw.edu.pl
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01628-2

9120
substituents can be introduced at the primary or secondary rim of the cyclodextrin torus.
Amphiphilic cyclodextrins which have been described so far, include per-derivatives with
3
4
5
alkyl-amino, alkyl-thio, and alkyl-sulfoxo substituents at the primary positions of each
glucose unit of the cyclodextrin. The second type of amphiphilic cyclodextrin possesses the
6
7
hydrophobic functionality attached to the secondary hydroxyl position by an ester or ether
linkage. Long alkyl chains (five–seven carbon atoms) attached via an ether linkage were chosen
to introduce lipophilic character to the secondary face of the cyclodextrin molecule. In our
synthetic approach (Scheme 1), we have regioselectively 6-O-protected the starting a- and
8
b-cyclodextrins using tert-butyldimethylsilyl chloride in pyridine. Treatment of 1 with a 10-fold
excess of alkyl (n-pentyl, n-hexyl, n-heptyl) iodide in DMF in the presence of a 12-fold excess
9
of sodium hydride for
3
days, gave per(6-O-tert-butyldimethylsilyl-2,3-di-O-alkyl)-
cyclomaltooligosaccharides (3a–c) and (4a–c). Derivatives 3a–c and 4a–c were desilylated using
10
a standard procedure (tetrabutylammonium fluoride in boiling tetrahydrofuran) to give
amphiphilic per(2,3-di-O-alkyl)-a, b-cyclodextrins (5a–c) and (6a–c). All the free hydroxy groups
at position C-6 were exchanged to iodo functions by treatment with a toluene solution of
11
triphenylphosphine/I and stoichiometric amounts of imidazole, to give per(6-deoxy-6-iodo-
2
2
,3-di-O-alkyl) derivatives (7a–c) and (8a–c). The S-alkylation reactions between an excess of
benzyl mercaptan and per(6-deoxy-6-iodo) cyclodextrin derivatives 7a–c or 8a–c, were carried
using 3 M sodium methoxide at 60°C in DMF for 24 h to give hexakis(6-thiobenzyl-6-deoxy-2,3-
†
di-O-alkyl)cyclomaltohexaoses (9a–c) in 94, 95, and 85% yield, respectively and heptakis(6-
‡
deoxy-6-S-benzyl-2,3-di-O-alkyl)cyclomaltoheptaoses (10a–c). S-Benzyl functionalities were
introduced at the primary rim of the amphiphilic cyclodextrins in order to recover the anchoring
SH groups by the reductive cleavage of benzyl groups using sodium in liquid ammonia to give
†
22
13
Hexakis(6-deoxy-6-S-Bzl-2,3-di-O-alkyl) a-CD selected data: 9a oil, [h]D +139.0° (c 1, CHCl3); C NMR
CDCl ) l 97.80 (C-1), 81.13 (C-4), 80.08, 71.74 (C-2,3,5), 33.59 (C-6), 37.69 (CH ꢀPh), 138.93, 129.07, 128.24, 126.65
(
(
3
2
Aromatic), 73.92, 71.58 (2×C H ), 30.21, 29.97 (2×C H ), 28.26, 28.19 (2×C H ), 22.81, 22.65 (2×C H ), 14.07, 14.04
2×C H ); LSIMS(+) NBA m/z 2450.2 [M+H] , calc. for C138H216O S 2450.4 [M+H] . Compound 9b oil, [h]
3 24 6 D
107.4° (c 1, CHCl3); C NMR (CDCl ) l 97.96 (C-1), 81.28 (C-4), 80.16, 80.05, 71.79 (C-2,3,5), 33.62 (C-6), 37.72
h
2 i 2 k 2 l 2
+
+
22
(
+
d
13
3
(
(
CH ꢀPh), 138.97, 129.12, 128.29, 126.69 (Aromatic), 74.02, 71.70 (2×C H ), 32.10, 31.90 (2×C H ), 30.56, 30.28
2
h
2
i
2
2×C H ), 25.85, 25.74 (2×C H ), 22.77, 22.70 (2×C H ), 14.08, 14.05 (2×C H ); LSIMS (+) NBA m/z 2618.0
k
2
+
l
2
m
2
d
3
+
24 6 D 3
22
13
[
M+H] , calc. for C150H240O S 2620.6 [M+H] . Compound 9c oil, [h] +212.2° (c 1, CHCl3); C NMR (CDCl ) l
9
8.00 (C-1), 81.36 (C-4), 80.18, 80.00, 71.81 (C-2,3,5), 33.60 (C-6), 37.72 (CH ꢀPh), 138.98, 129.12, 128.28, 126.69
2
(
Aromatic), 74.03, 71.70 (2×C H ), 32.08, 31.95 (2×C H ), 30.66, 30.34 (2×C H ), 29.66, 29.40 (2×C H ), 26.21, 26.04
h
2 i 2 k 2 l 2
+
d
(
2×C H ), 22.70, 22.69 (2×C H ), 14.10(d) (2×C H ); LSIMS (+) NBA m/z 2788.8 [M+H] , calc. for C162H264O S6
2 2 3 24
m
x
+
2789.2 [M+H] .
‡
22
13
Heptakis(6-deoxy-6-S-Bzl-2,3-di-O-alkyl) b-CD selected data: 10a oil, [h]D +220.9° (c 1, CHCl3); C NMR
CDCl ) l 97.83 (C-1), 80.91 (C-4), 80.23, 80.02, 71.75 (C-2,3,5), 33.66 (C-6), 37.69 (CH ꢀPh), 138.85, 129.06, 128.30,
(
1
3
2
26.65 (Aromatic), 73.98, 71.54 (2×C H ), 30.18, 29.91 (2×C H ), 28.32, 28.17 (2×C H ), 22.82, 22.62 (2×C H ),
h
2 i 2 k 2 l 2
+
28 7
+
1
4.07 (2×C H ); LSIMS (+) NBA m/z 2859.5 [M+H] , calc. for C161H252O S 2861.2 [M+H] . Compound 10b oil,
d
3
22
13
D 3
[
h] +112.5° (c 1, CHCl3); C NMR (CDCl ) l 97.90 (C-1), 80.99 (C-4), 80.29, 80.05, 71.78 (C-2,3,5), 33.67 (C-6),
3
3
7.71 (CH ꢀPh), 138.88, 129.11, 128.35, 126.71 (Aromatic), 74.10, 71.68 (2×C H ), 32.13, 31.87 (2×C H ), 30.54,
2
h
2
i
2
0.23 (2×C H ), 25.93, 25.72 (2×C H ), 22.77, 22.73 (2×C H ), 14.09, 14.07 (2×C H ); LSIMS (+) NBA m/z 3054.0
k
2
l
2
m
2
d
2
+
+ 22
28 7 D
13
[
M+H] , calc. for C175H280O S 3057.8 [M+H] . Compound 10c oil, [h] +94.6° (c 0.56, CHCl3); C NMR (CDCl3)
l 97.92 (C-1), 81.03 (C-4), 80.32, 80.05, 71.71 (C-2,3,5), 33.67 (C-6), 37.71 (CH ꢀPh), 138.88, 129.11, 128.35, 126.71
2
(
(
Aromatic), 74.13, 71.71 (2×C H ), 32.07, 31.98 (2×C H ), 30.65, 30.30 (2×C H ), 29.69, 29.39 (2×C H ), 26.27, 26.03
h
2 i 2 k 2 l 2
+
2×C H ), 22.70 (2×C H ), 14.10 (2×C H ); LSIMS(+) NBA m/z 3254.9 [M+H] , calc. for C189H308O S 3253.9
m
2
+
x
2
d
2
28 7
[
M+H] .

9121
Scheme 1.

9122
§
hexakis(6-deoxy-6-thio-2,3-di-O-pentyl)cyclomaltohexaoses (11). Compound 11 has two impor-
tant properties: the ability to act as an amphiphile and the ability for chemisorption on metal
substrates. The electrochemical studies of the modified surfaces are in progress now in our
laboratory.
¶
The surface pressure−mean molecular area (y−A) isotherms indicate that the amphiphilic
cyclodextrin derivatives 5a, 5c, 6c, and 11 are capable of forming monolayers at the air–water
interface. The isotherms recorded for these cyclodextrin derivatives are shown in Fig. 1. The
compounds formed stable monolayers with high collapse pressure. The collapse pressure values
for 5a, 5c, 6c were close to 42 mN/m, whilst the monolayer formed by 11 collapsed at a lower
pressure of 21 mN/m. The extrapolated areas per molecule at zero pressure of 5a, 5c, 6c, 11,
2
were 2.66, 2.77, 3.74, 3.44 nm , respectively. Substitution of all primary ꢀOH groups of
2
a-cyclodextrin derivatives by ꢀSH groups lead to increase of molecular area (2.66 nm for 5a and
2
3
.44 nm for 11). The isotherms were typical of a solid-like monolayer, except for compound 11,
which formed a more liquid monolayer. This difference was connected with the lower stability
Figure 1. Surface pressure–area isotherms for compounds 5a, 5c, 6c and 11 on pure water
§
22
13
Hexakis(6-deoxy-6-thio-2,3-di-O-pentyl) a-CD selected data: 11a [h]D +94.7° (c 0.9, CHCl3); C NMR (CDCl3)
l 98.19 (C-1), 81.27 (C-4), 80.07, 80.01 (C-2,3), 74.02, 71.80 (2×C H ), 71.14 (C-5), 30.26, 29.97 (2×C H ), 28.31,
h
2
i
2
+
2
8.19 (2×C H ), 27.51 (C-6), 22.84, 22.66 (2×C H ), 14.11, 14.06 (2×C H ); LSIMS(+) NBA m/z 1908.2 [M+H] ,
k
2 l 2 d 3
+
181 24 6
calc. for C H O S 1910.1 [M+H] .
96
¶
All solutions were prepared by dissolving the cyclodextrin derivatives (5a, 5c, 6c, 11) in pure chloroform (c=1.2
mg/ml). Distilled water used as the subphase was passed through a Milli-Q water purification system. The y−A
isotherms were recorded using the KSV Langmuir–Blodgett Trough 5000 equipped with two barriers, and Wilhelmy
balance as a surface-pressure sensor. To protect the experimental setup from dust it was placed in the laminar flow
2
hood in which temperature was kept constant 20±1°C. The accuracy of measurements was ±0.1 nm for area per
molecule, ±1 mN/m for surface pressure. The procedures of cleaning the trough and monolayer spreading have been
12
described earlier.

9123
of the thiol monolayers on the air–water interface due to less polar properties of the –SH
13
terminal group compared to the more polar hydroxyl headgroups of the other amphiphiles.
Acknowledgements
Financial support from the Warsaw University (BST-623/14/99) and from the Institute of
Organic Chemistry, Polish Academy of Sciences, is gratefully acknowledged.
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