SYNTHESIS AND COMPLEXATION OF N-METHYLBENZOAZACROWN
Group I, II metal cations and ammonium ions and allow one to
predict their use in effective optical molecular sensors.
through a thin Al2O3 layer using benzene and then EtOAc as the
eluents. The yield of 1c was 9 mg (58%).
10-Methyl-2,3,5,6,9,10-hexahydro-8H-1,4,7,10-benzotriox-
azacyclododecine-13-carbaldehyde (1a). Mp 71–72 8C (hex-
ane), mp 71–72 8C.[14] 1H NMR (DMSO-d6, 30 8C) d: 2.85 (s, 3H,
MeN), 3.48 (t, J ¼ 7.3, 2H, CH2N), 3.59 (m, 2H, CH2O), 3.67 (m, 2H,
CH2O), 3.82 (t, J ¼ 7.3, 2H, CH2CH2N), 3.84 (m, 2H, CH2CH2OAr),
4.15 (m, 2H, CH2OAr), 6.89 (d, J ¼ 8.3, 1H, H(11)), 7.29 (d, J ¼ 1.8,
1H, H(14)), 7.42 (dd, J ¼ 8.3, J ¼ 1.8, 1H, H(12)), 9.72 (s, 1H, CH ¼ O).
13-Methyl-2,3,5,6,8,9,12,13-octahydro-11H-1,4,7,10,13-
benzotetraoxazacyclopentadecine-16-carbaldehyde (1b). Mp
49–51 8C (hexane), mp 50–51 8C.[14] 1H NMR (DMSO-d6, 30 8C) d:
2.87 (s, 3H, MeN), 3.30 (t, J ¼ 7.5, 2H, CH2N), 3.57 (s, 4H, 2CH2O),
3.60 (m, 4H, 2CH2O), 3.82 (m, 2H, CH2CH2OAr), 3.86 (t, J ¼ 7.5, 2H,
CH2CH2N), 4.14 (m, 2H, CH2OAr), 6.92 (d, J ¼ 8.3, 1H, H(14)), 7.29 (d,
J ¼ 1.5, 1H, H(17)), 7.42 (dd, J ¼ 8.3, J ¼ 1.5, 1H, H(15)), 9.73 (s, 1H,
CH ¼ O).
EXPERIMENTAL
General information
40-Formylbenzo-12(15,18)-crown-4(5,6) ethers (2a–c)[21,22] and
N-(4-formylphenyl)aza-15(18)-crown-5(6) ethers (9a,b)[23] were
obtained by known methods. CD3CN (water < 0.05%), NaH (60%
in paraffin), THF (water < 0.005%) were used as received (Merck,
Aldrich, or Fluka). NaClO4, KClO4, Ca(ClO4)2 and Ba(ClO4)2 (Aldrich)
were dried in vacuo at 200 8C, NH4ClO4 and EtNH3ClO4 were dried
at 70 8C.
The melting points measured with a MEL-Temp II apparatus in
a capillary are uncorrected. The 1H NMR spectra were recorded on
a Bruker DRX500 (500.13 MHz) instrument in DMSO-d6 and
CD3CN solutions using the solvent as an internal reference (2.50
and 1.96 ppm, respectively). The course of the reactions was
monitored by TLC on DC-Alufolien Kieselgel 60 F254 plates
(Merck). Column chromatography was performed with silica gel
(Kieselgel 60, 0.063–0.100 mm, Merck) and aluminium oxide
(Aluminiumoxid 90, aktiv neutral, 0.063–0.200 mm, Merck).
Elemental analyses were performed at the microanalytical
laboratory of the A. N. Nesmeyanov Institute of Organoelement
Compounds in Moscow, Russia.
16-Methyl-2,3,5,6,8,9,11,12,15,16-decahydro-14H-
1,4,7,10,13,16-benzopentaoxazacyclooctadecine-19-carbal-
dehyde (1c). Yellowish oil.[14] 1H NMR (DMSO-d6, 30 8C) d: 2.95 (s,
3H, MeN), 3.50 (t, J ¼ 5.9, 2H, CH2N), 3.52 (m, 4H, 2CH2O), 3.54 (s,
4H, 2CH2O), 3.60 (s, 4H, 2CH2O), 3.72 (t, J ¼ 5.9, 2H, CH2CH2N), 3.80
(m, 2H, CH2CH2OAr), 4.14 (m, 2H, CH2OAr), 6.89 (d, J ¼ 8.2, 1H,
H(17)), 7.29 (d, J ¼ 1.4, 1H, H(20)), 7.42 (dd, J ¼ 8.2, J ¼ 1.4, 1H,
H(18)), 9.73 (s, 1H, CH ¼ O).
Synthesis of complexes of crown ethers 1b,c with Ba(ClO4)2
(general procedure). A solution of 1b,c (30 mmol) and Ba(ClO4)2
(10 mg, 30 mmol) in acetonitrile (3 ml) was slowly saturated with
benzene by vapour diffusion methods (for 2–3 weeks). The single
crystals formed were collected by decantation and dried in air at
room temperature. The crystals were characterized by elemental
analysis and used for X-ray structural study.
Preparation
Synthesis of benzoazacrown ethers 1a–c (general procedures).
Method A
Complex 1b ꢁ Ba(ClO4)2. Obtained as colourless blocks in 89%
yield; mp > 330 8C (decomp.). Anal. calcld for C16H23BaCl2NO13: C,
29.77; H, 3.59; N, 2.17; found: C, 29.84; H, 3.54; N, 2.19%.
Complex 1c ꢁ Ba(ClO4)2. Obtained as colourless blocks in 65%
yield; mp 302–305 8C (decomp.). Anal. calcld for C18H27BaCl2NO14:
C, 31.35; H, 3.95; N, 2.03; found: C, 31.26; H, 3.84; N, 2.04%.
A mixture of iodide 5a–c (0.1 mmol), anhydrous THF (7 ml) and
40 mg (1 mmol) of 60% NaH in paraffin was refluxed with stirring
for 30 min. After cooling, the reaction mixture was diluted with
water and extracted with benzene. The extracts were washed
with water and concentrated in vacuo, and the residue was
purified by column chromatography on SiO2, using successively a
1: 1 benzene–EtOAc mixture and EtOAc as the eluents to give
1a–c as light yellow oils, from which 1a and 1b crystallized on
standing. The yields of 1a–c are presented in Table 1.
1H NMR titration
The titration experiments were performed in CD3CN solutions at
30 ꢄ 1 8C. A solution of crown ether (L) (0.5 ml, CL ¼ 5 ꢅ 10ꢀ3 M)
and NaClO4, Ca(ClO4)2, Ba(ClO4)2, or EtNH3ClO4 (CM ¼ 0.03 M)
were added in portions to a solution of L in CD3CN (0.5 ml,
CL ¼ 5 ꢅ 10ꢀ3 M). In the case of NH4ClO4 and KClO4,
CL ¼ 2 ꢅ 10ꢀ3 M and CM ¼ 0.012 M were used for titration due
to the low solubility of the salts in CD3CN. In the case of
competitive titration, a solution (0.5 ml) containing a mixture of L,
metal perchlorate and the competing ligand (L’) (CL ¼ 5 ꢅ 10ꢀ3 M,
CM ¼ 6 ꢅ 10ꢀ3 M, CL’ ¼ 0.2 M) was added in portions to a solution
of a mixture of L and metal perchlorate in CD3CN (0.5 ml,
CL ¼ 5 ꢅ 10ꢀ3 M, CM ¼ 6 ꢅ 10ꢀ3 M). The proton chemical shifts
were measured as a function of the M/L or L’/L ratio and the
complex formation constants were then calculated using the
HYPNMR program.[17]
Method B
A mixture of iodide 5a–c (0.1 mmol), anhydrous THF (7 ml) and
60% NaH (40 mg, 1 mmol) in paraffin was stirred at room
temperature until the initial iodide disappeared (TLC monitoring).
The mixture was worked-up as in Method A. The reaction time and
the yields of 1a–c are presented in Table 1.
Method C
A mixture of chloride 4b,c (0.1 mmol), anhydrous THF (7 ml) and
60% NaH in paraffin (40 mg, 1 mmol) was refluxed with stirring
until the initial chloride disappeared (TLC monitoring). The
workup was similar to that in Method A. The reaction time and the
yields of 1b,c are presented in Table 1.
Methylation of benzoazacrown ether 6c. A mixture of
azacrown ether 6c (15 mg, 44 mmol), 60% NaH (35 mg, 0.88 mmol)
in paraffin, MeI (27 ml, 0.44 mmol) and anhydrous THF (4 ml) was
refluxed for 30 min. The reaction mixture was diluted with water
and extracted with benzene. The extracts were washed with
water and concentrated in vacuo and the residue was passed
X-ray experiments
Crystals of compounds 1b, 9a,b and 10 ꢁ CH2Cl2 were obtained by
slow evaporation of the CH2Cl2–hexane solutions. Crystals of
J. Phys. Org. Chem. 2009, 22 823–833
Copyright ß 2009 John Wiley & Sons, Ltd.