Synthesis of a new stable peristatic chiral pseudocryptand for simultaneous binding of boron and sodium

Article abstract of DOI:10.1002/jhet.5570420626

A new selective molecular receptor, borocryptate, based on the combination of the 15 membered ring diazatrioxa core and two saligenin units as binding sites for boron has been described. The resulting peristatic chiral compound is stable in air and easily

Full text of DOI:10.1002/jhet.5570420626

Synthesis of a New Stable Peristatic Chiral Pseudocryptand for
Simultaneous Binding of Boron and Sodium
Sep-Oct 2005
1201
a
b
c
a
Mahmut Tog˘rul *, Giray Topal , Mürüvvet Yurdakoç and Halil Hos¸gören
a
Department of Chemistry, Faculty of Science, Dicle University, 21280 Diyarbakır, Turkey
b
Department of Chemistry, Faculty of Education, Dicle University, 21280 Diyarbakır, Turkey
c
Department of Chemistry, Faculty of Science, Dokuz Eylul University, Izmir, Turkey
Received December 24, 2004
A new selective molecular receptor, borocryptate, based on the combination of the 15 membered ring
diazatrioxa core and two saligenin units as binding sites for boron has been described. The resulting perista-
tic chiral compound is stable in air and easily converted to polynuclear complex, Na-borocryptate, without
using an inert atmosphere.
J. Heterocyclic Chem., 42, 1201 (2005).
Introduction.
connected by polyethylene glycol spacers have been also
reported [13].
Since the discovery of cryptands, in particular the [2.2.2]
macrobicyclic ligand L1, some 30 years ago by Dietrich,
Lehn and Sauvage [1] and of the crown ethers by Pedersen
[2] an exciting new field of research named supramolecu-
lar chemistry has opened to inorganic, organic and physi-
cal chemists [3-5]. Whereas at the outset much attention
was focused on the selective binding of monoatomic alka-
line and alkaline-earth metal cations, very rapidly consid-
erable achievements were reported with regard to the
recognition of molecular cations [6].
However, during the preparation of borocryptand, it was
observed that if oxygen was not completely removed, the
reaction afforded a pink precipitate that resulting from the
oxidation of the catechol moieties prior to binding of
boron. Probably this is due to the strong basicity of its
macrocyclic core promoting an intramolecular proton
transfer from catechol moieties to the tertiary amino
groups and thus generating the catecholate ammonium
zwitter ion, which is extremely sensitive to oxidation and
hence should be stored in the absence of oxygen.
Many aspects of supramolecular chemistry remain to be
developed, for example new materials based on self
assembly may be targeted by using weak interactions [7].
On the other hand, the design and synthesis of bi-nuclear
complexes have been extensively studied over the past
three decades [7]. In these complexes, intrinsic molecular
properties such as magnetic coupling, redox activity and
optical features may be tuned with remarkable precision
[8]. Although at an earlier period many homo- and heter-
obinuclear complexes reported were essentially of the
same type, i.e. two alkaline or two transition metal cations,
only recently considerable afford has been invested in the
synthesis of heterobinuclear complexes possessing both a
hard alkaline or alkaline-earth and soft transition metal
cations [9]. Inspiring from structural aspects of boromycin
[10] and aplasmomycin [11], natural antibiotics bearing a
spiroborate group and of cryptands, Hosseini and co-work-
ers have embarked upon a program dealing with the design
and synthesis of polynucleating ligands.
Therefore, to prevent the oxidation of the ligand L2
complexation must be carried out under inert atmosphere,
such as argon [14].
Results and Discussion.
Their approach to the design of binucleating receptor
was based on the combination of a macrocyclic framework
and two bidentate dianionic ligands. Using preorganised
cores, such as diaza-macrocyclic, bi- and polynucleating
ligands bearing bidentate catechol units have been pre-
pared [12]. For the macrocyclic core, a diazamacrocyclic
ring was chosen because of its ability to bind hard cations.
For this reason, Hosseini and co-workers have designed a
new family of artificial receptor for alkaline metal cations
[12a]. Compounds in which two catechol units were inter-
In the present contribution a new sodium receptor based
on the combination of the 15 membered ring diazatrioxa
macrocyclic core and two saligenin units instead of [2.2]
macrocyclic cores and catechol moieties in L2 was
designed (3-B, Na). The saligenin moieties provide binding
sites for boron as catechol, but it also makes the ligand more
stable against air oxidation. The sodium borocryptant syn-
thesis was prepared as shown in Scheme 1. In the L2 ligand,
one of the two phenolic hydroxyl groups is converted to
saligenin in the case of L3. Replacement of catechol units,

1202
M. Tog˘rul, G. Topal, M. Yurdakoç and H. Hos¸gören
Vol. 42
1
13
acting as binding sites for boron, with saligenin moieties con-
tributes to the stability of L3 over L2 against air oxidation.
was determined by H and C NMR spectroscopy in
13
1
and C signals
CDCl . For the complex (3-B, Na) all H
3
Scheme 1
1
13
The free ligand L3 was converted to (3-B, Na) complex
without using inert atmosphere. The binding ability of
receptor L3 towards boron and sodium was achieved by
treating the free ligand L3 with 1 eq. of NaOH and 1 eq. of
were assigned based on a H- C NMR correlation experi-
1
13
ment (Figure 1). Comparison of the H and C NMR
spectra of free ligand L3 and its complex produces surpris-
ing results, not only in chemical shifts but also in the num-
ber of signals. Based on this observations, the proton and
carbon chemical shift for the alkali metal complexes of
type (3-B, Na) were strongly depend on the nature of the
B(OH) in H O/EtOH mixture at room temperature afford-
3
2
ing the (3-B, Na) complex as a white precipitate which was
filtered and recrystallised from methanol. The (3-B, Na)
complex was perfectly stable towards oxidation and could
be stored in the presence of oxygen. The structure of L3
1
cation [12b]. H NMR of ligand L3 gave signals at 1.16
ppm as a singlet, 2.63-2.68 ppm as a
triplet, 2.72-274 ppm
1
13
Figure 1. H- C corelation spectra of (3-B, Na).

Sep-Oct 2005
Synthesis of a New Stable Peristatic Chiral Pseudocryptand
1203
as a triplet, 3.65 ppm as a singlet, 4.56 ppm as a singlet,
PhCH N, PhCH O protons, respectively (Figure 2). Upon
2
2
corresponding to tertiary butyl groups, CH N, CH O,
complexation, tertiary butyl groups appear at 1.24 and 1.27
2
2
1
Figure 2. H NMR spectra of L3.
1
Figure 3. H NMR spectra of (3-B, Na) (Doubled peaks were shown in spectrum).

1204
M. Tog˘rul, G. Topal, M. Yurdakoç and H. Hos¸gören
Vol. 42
give as a white crystals of 5a (25.2 g, 75%), mp 75-75.5°C. ir: ν
ppm as two singlets while both PhCH N and PhCH O
2
2
3401, 3308, 3068, 3034, 2956, 2874, 1606, 1486, 1463, 1363,
peaks appears as AB quartets. And also OCH CH O pro-
2
2
-1
1264, 1216, 1064, 1011, 870 cm .
tons gave a multiplet at 3.46-3.50 ppm (Figure 3).
Anal. Calcd for: C
H O ; C, 68.57; H, 8.57. Found: C,
13
12 28 3
As to C NMR spectra, the free ligand L3 gave 9 and 6
peaks for aliphatic and aromatic region but in (3-B, Na)
complex, 18 and 12 peaks were observed respectively, i.e,
the number of carbon peaks in free ligand L3 doubled
68.48; H, 8.41.
4-tert-Butyl-2,6-Dihydroxymethyl Phenyl Benzyl Ether (5b).
4-tert-Butyl-2,6-dihydroxy-methyl phenol 5a (17 g, 0.081
+
mol) was dissolved in absolute ethanol and then K CO (11.18 g,
upon complexation with Na .
2
3
0.081 mol) was added to the mixture. Benzylchloride (10.24 g,
0.081 mol) was added dropwise to the solution. The mixture was
refluxed for 18 hours. Then, the mixture was filtered and ethanol
was evaporated. The product crystallised from ether-petrolium
ether mixture, to give as a white crystals of 5b (17g, 70%), mp
98-100°C. ir: ν 3551, 3460, 3275, 3063, 3034, 2950, 2903, 2865,
1606, 1482, 1454, 1381, 1361, 1301, 1240, 1199, 1118, 1062,
This observation might be explained in terms of tetrahe-
dral nature of boron complex resulted in a peristatic chiral
[12c,15] structure. Schematic representation of R and S enan-
tiomers obtained upon complexation of boron in tetrahedral
geometry by the ligand (3-B, Na) is shown in Figure 4.
In summary, high yield synthesis of L3 that is very sta-
ble against air oxidation based on the macrocyclic back-
bone bearing two saligenin units was achieved. The bind-
ing ability of L3 towards both boron and sodium cation
was analysed by NMR spectroscopy.
-1
1011, 886, 739, 700 cm .
Anal. Calcd. For: C
H O ; C, 75.97; H, 8.05. Found: C,
19 24 3
76.18; H, 8.15.
4-tert-Butyl-2-hydroxymethyl-6-Chloromethyl Phenyl Benzyl
Ether (5c).
A solution of 4-tert-butyl-2,6-dihydroxymethyl phenyl ben-
zyl ether 5b (16.75 g, 0.056 mol) and pyridine (4.74 g, 0.06
mol) in absolute benzene (350 mL), was stirred with reflux.
Thionyl chloride (6.64 g, 0.056 mol) was added to the solution
dropwise in three hours and then left for 16 hours with reflux.
The mixture was cooled to the room temperature and filtered.
After then, 1.5 mL concentrated hydrochloric acid and 25 mL
water was added. The resulting organic phase was washed with
water. The benzene extract was dried over Na SO and evapo-
2
4
rated. The residue was purified by column chromatography on
silica gel eluted with petrolium ether/ether (2:1). After column
chromatography the product recrystallised from ether-
petrolium ether to give as a white crystal of 5c (9.4 g, 50%),
mp 77-77.5 °C; ir: ν 3579, 3486, 3029, 2960, 2898, 2875,
1584, 1476, 1454, 1385, 1362, 1268, 1256, 1204, 1113, 979,
Figure 4. Schematic representation of both R and S enantiomers obtained
upon complexation of boron in tetrahedral coordination geometry by the
ligand (3-B, Na).
EXPERIMENTAL
-1
1
886, 733, 694, 633 cm ; H nmr (CDCl ): δ 1.38 (s, 9H); 1.92
3
(bs, 1H); 4.71 (s, 2H); 4.74 (s, 2H); 5.07 (s, 2H); 7.44-7.53 (m,
General Information.
13
7H); C nmr (CDCl ): δ 31.81, 34.94, 41.85, 61.77, 73.39,
3
1
127.63, 128.24, 128.48, 128.82, 129.12, 130.90, 134.32,
137.40, 148.36, 153.29 ppm.
The H nmr spectra were obtained at 400 MHz on a BRUKER
DPX-400 High Performance Digital FT-NMR in CDCl with
3
13
Anal. Calcd. for: C
H O Cl: C, 71.59; H, 7.22; found: C,
TMS as the internal standard. The C nmr spectra were obtained
19 23 2
71.57; H, 7.35.
at 100 MHz on a BRUKER DPX-400 High Performance Digital
FT-NMR. The elemental analyses were obtained with CARLO-
ERBA Model 1108 apparatus. Infrared spectra were recorded on
a MIDAC-FTIR Model 1700 Spectrophotometer. Melting points
were determined with a GALLENKAMP Model apparatus with
open capillaries. Mass spectra data were recorded with an AGI-
LENT 1100 MSD spectrometer.
Second product recrystallised from ether-petrolium ether to
give as a white crystal of 4-tert-butyl-2,6-dichloromethyl phenyl
benzyl ether 5d, mp 80-82 °C. ir: ν 3095, 3068,3038, 2964, 2867,
1500, 1481, 1465, 1455, 1381, 1364, 1270, 1210, 1108, 982, 891,
-1 1
781, 696, 637 cm ; H nmr (CDCl ):δ 1.38 (s, 9H); 4.69 (s, 4H);
3
13
5.14 (s, 2H); 7.28-7.58 (m, 7H); C nmr (CDCl ): δ 31.73, 34.93,
41.72, 77.58, 128.78, 129.09, 129.36, 131.32,137.34, 148.53,
153.53 ppm.
3
4-tert-Butyl-2,6-Dihydroxymethyl Phenol (5a).
Tert-butyl phenol 5 was converted to the 5a according to the
literature method [16]. Tert-butyl phenol 5 (24 g, 0.16 mol),
40% aqueous formaldehyde (24 g, 0.32 mol) and 2% aqueous
NaOH (320 g, 0.16 mol) was stirred at 30-40 °C for 30-50
Anal. Calcd. For: C
64.52; H, 6.28.
H OCl ; C, 64.59; H, 6.23. Found: C,
19 22 2
Saligenin Armed Diaza-15-Cr-5 Derivative L3
(Pseudocryptand).
hours. Then 25% of H SO solution (31.32 g, 0.16 mol) was
2
4
added to the mixture. The resulting organic phase was extracted
with ethers (3 x 50 mL). The ethers extract was dried over
Commercially available diaza-15-Cr-5 (6) (1.0 g, 45.87 mmol)
and 4-tert-butyl-2-hydroxymethyl-6-chloromethyl phenyl benzyl
Na SO and solvent was evaporated with rotary evaporator.
ether 5c (4.64 g, 45.87 mmol) in the presence of Et N was dis-
2
4
3
The product crystallised from ether-petroleum ether mixture to
solved in toluene (75 mL). The mixture was stirred at 80-85 °C for

Sep-Oct 2005
Synthesis of a New Stable Peristatic Chiral Pseudocryptand
1205
mtogrul@dicle.edu.tr
[1] B. Dietrich, J. M. Lehn, J. P. Sauvage, Tetrahedron
Lett., 34 , 2885 (1969).
[2] C. J. Pedersen, J. Am. Chem. Soc., 89, 7017 (1967).
[3] C. J. Pedersen, Angew. Chem. Int. Ed. Engl., 27, 1053,
(1988).
[4] D. J. Cram, Angew. Chem. Int. Ed. Engl., 27, 1041,
(1988).
16 hours. Then mixture was cooled and filtered. After the evapora-
tion the crude product was obtained as an oil of L4 (3.26 g, 91%).
This crude residue was directly debenzylated with Pd/C in dry
ethanol- ethyl acetate mixture. The compound L3 was obtained as
1
a colourless liquid in almost quantitative yield. H nmr (CDCl ): δ
3
1.16 (s, 18H); 2.65-2.75 (m, 8H); 3.46-3.67 (m, 16H); 4.56 (s, 4H);
13
4.66 (bs, 4H); 7.07 (dd, 4H); C nmr (CDCl ): δ 18.40, 31.87,
3
34.21, 54.55, 54.67, 57.77, 59.74, 61.98, 68.50, 69.11, 70.77,
124.84, 125.00, 125.18, 127.45, 141.77, 153.65 ppm.
[5] J. M. Lehn, Angew. Chem. 100, 91, (1988); Angew.
Chem. Int. Ed. Engl., 27, 89, (1988).
Anal. Calcd. for: C
H N O ; C,67.55; H, 9.27; N, 4.64.
34 56 2 7
[6] F. Vögtle, Supramolecular Chemistry, Wiley,
Chichester, (1991).
[7] R. M. Izatt, K. Pawlak, J. S. Bradshaw, Chem. Rev. 91,
1721, (1991).
[8] P. Zanello, S. Tamburini, P. A. Vigato, G. A.
Mazzocchin, Coord. Chem. Rev., 77, 165, (1987); D. C. Smith, H.
B. Gray, Chem. Rev., 100, 169, (1990).
[9] F. C. J. M. Van Veggel, W. Verboom, D. N. Reinhoudt,
Chem.Rev. 94, 279, (1994).
[10] R. Hütter, W. Keller-Schierlein, F. Knüsel, V. Prelog, G.
C. Rodgers, P. Sutter, G. Vogel, W. Voser, H. Zahner, Helv. Chim.
Acta, 50, 533, (1967).
[11] T. Okazaki, T. Kitahara, Y. Okami, J. Antibiotics, 28,
176, (1975).
[12a] E. Graf, M.W. Hosseini, R. Ruppert, Tetrahedron Lett.
35, 7779, (1994); [b] E. Graf, M.W. Hosseini, R. Ruppert, N.
Kyritsakas, A. De Cian, J. Fischer, C. Estournes, F. Taulelle,
Angew. Chem. Int. Ed. Engl., 34, 1115 (1995); [c] E. Graf, M. W.
Hosseini, R. Ruppert, A. De Cian, J. Fischer, J.C.S.,Chem.
Comm., 1505, (1995); E. Graf, M. W. Hosseini, A. De Cian, J.
Fischer, J. Bull. Soc. Chim. Fr. 133, 743, (1996); C. Drexler, M.
W. Hosseini, A. De Cian, J. Fischer, Tetrahedron Lett. 38, 2993,
(1997); E. Graf, M. W. Hosseini, R. Ruppert, Tetrahedron Lett.,
35, 7779, (1994).
Found: C, 67.42; H, 9.34; N, 4.58.
Sodium Borocryptate (3-B, Na).
The benzyl protected ligand L4 was debenzylated as
described in literature [17]. A mixture of L4 (3.26 g, 4.17
mmol) and 0.25 g of preequilibrated 10% palladium/carbon in
75 ml ethanol/ethylacetate (2:1) was hydrogenated at room
temperature and atmospheric pressure. Hydrogen absorption
ceased after the uptake to afford L3. The free L3 (2.51 g, 4.17
mmol) dissolved in ethanol and treated with 1 eq. of NaOH
and 1 eq. of B(OH) in H O/EtOH mixture at room tempera-
3
2
ture affording the (3-B, Na) complex as a precipitate which
was filtered and recrystallised from methanol. The compound
(3-B, Na) was obtained as a white crystal in almost quantita-
tive yield, mp 310 °C decomposed. MS: m/z (M +1, 633.4) ir:
ν 3384, 2952, 2870, 2825, 1613, 1485, 1365, 1281, 1263,
1219, 1112, 1040, 1007, 935, 884, 791, 643, 620 cm ; H nmr
+
-1 1
(CDCl ): δ 1.24 (s, 9H); 1.27 (s, 9H); 2.33-3.03 (m, 8H); 3.28-
3
4.12 (m, 12H); 3.52 (dd, 2H); 3.55 (dd, 2H); 4.78 (dd, 2H);
13
5.00 (dd, 2H); 6.87 (dd, 4H); C nmr (CDCl ): δ 32.11,
3
34.12, 34.15, 50.79, 53.71, 54.85, 55.57, 58.18, 58.51, 61.38,
62.81, 63.62, 67.18, 67.28, 68.40, 68.76, 69.05, 69.20, 121.95,
122.05, 123.63, 125.03, 125.32, 125.38, 125.87, 126.92,
139.53, 139.69, 152.78, 152.90 ppm.
[13] Y. Kebuke, Y. Sumida, M. Hayashi, H. Ogoshi, Angew.
Chem. Int. Ed. Engl., 30, 1496, (1991).
Anal. Calcd. for: C
Found: C, 64.12; H, 8.37; N, 4.34.
H N O BNa; C, 64.35; H, 8.20; N, 4.42.
34 52 2 7
[14] F. Bockstahl, E. Graf, M. W. Hosseini, D. Suhr, A. De
Cian, J. Fischer, Tetrahedron Lett., 38, 7539, (1997).
[15] The adjective ‘peristatic’ (peristasis=environment) has
been suggested at the EUCHEM Conference on Stereochemistry
(Bürgenstock, may, 1966) by Professor S. D. Atkins.
[16] D. J. Beawer, R. S. Shumardu, P. J. Stoffel, J. Am.
Chem. Soc., 75, 5579, (1953).
Acknowledgement.
The financial support from University of Dicle (project no:
DÜAPK-03-FF-75) is greatly appreciated.
REFERENCES AND NOTES
[17] C. H. Heathcock, R. Ratcliffe, J. Am. Chem. Soc., 93,
1746, (1971).
*
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