Synthesis of bifunctional ligands based on azaheterocycles and fragments of 12-crown-4

Article abstract of DOI:10.1007/s11178-006-0020-1

Bifunctional ligands synthesized in this study are of interest for developing sensors based on SERS (Surface Enhanced Raman Spectroscopy). The function of 2,2′-bipyridyl and 1,10-phenanthroline fragments consists in formation of complexes with the metal surface, and the crown-fragment is meant for selective sensing of cations. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11178-006-0020-1

Russian Journal of Organic Chemistry, Vol. 41, No. 11, 2005, pp. 1690-1693. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 11, 2005,
pp. 1724-1727.
Original Russian Text Copyright Ó 2005 by Denisova, Degtyareva, Dem’yanchuk, Simanova.
.
.
Synthesis of Bifunctional Ligands Based on Azaheterocycles
and Fragments of 12-Crown-4
A.S. Denisova, M.B. Degtyareva, E.M. Dem’yanchuk, and A.A. Simanova
Research Institute of Chemistry, St. Petersburg State University, St. Petersburg, 198504 Russia
e-mail: anna@raman.org.ru
Received November 25, 2004
Abstract—Bifunctional ligands synthesized in this study are of interest for developing sensors based on SERS
(Surface Enhanced Raman Spectroscopy). The function of 2,2'-bipyridyl and 1,10-phenanthroline fragments consists
in formation of complexes with the metal surface, and the crown-fragment is meant for selective sensing of cations.
We report here on the synthesis of a series of hetero-
cyclic crown ethers containing fragments of 2,2'-bipyridyl
and 1,10-phenanthroline. Compounds obtained are
distinguished by the ability to rotate of the aromatic rings
of the heterocycle, by the nature of the donor atoms in
the crown-fragment, and by the mode of junction of these
parts of the bifunctional ligand.A crown ether with four
complexing atoms best fit to form complexes with lithium
cations was chosen for selective moiety.
The ion Li+ is held in the cavities of crown ethers with
the ring dimensions in the range from 12-crown-4 to
15-crown-4. However the simple crown ethers are not
selective toward Li+ ions in the presence of larger ions.
This is caused by formation of sandwich complexes
between the supporting ions (e.g., Na+) and two
molecules of the crown ether. To pervent the complexing
at the stoichiometric ratio 1:2 in solution or on the
membrane bulky substituents are included into the
molecule of the crown ether [1]. Under the SERS condi-
tions the molecules of bifunctional ligands are sorbed on
a metal surface (for instance, on silver or gold) with the
aid of heteroatoms (nitrogen, sulfur). If the heterocyclic
part of the molecule of the bifunctional ligand is rigidly
fixed on the surface the sandwich complexing with crown
fragments would presumably be avoided.
constitutes the crown-building element. The other
intermediate stages aim at preparation of compounds
based on 2,2'-bipyridyl and 1,10-phenanthroline capable
to react with the ditosylate affording the crown
derivatives.
EXPERIMENTAL
NMR spectra were registered at room temperature
on a spectrometer Bruker DPX 300 (1H and 13C NMR
spectra at operating frequencies 300 and 75 MHz respec-
tively). Elemental analyses were carried out on a CHN-
analyzer HP-185B.
Triethylene glycol ditosylate (II). To a solution of
10 ml (0.06 mol) of triethylene glycol (I) in 50 ml of freshly
distilled anhydrous THF cooled to 0°C in the presence of
10.86 g (0.194 mol) of KOH was added dropwise at
stirring within 1.5 h a solution of 26.1 g (0.137 mol) of
tosyl chloride in 43 ml of THF. The mixture obtained was
stirred for 5 h at 0°C, then for 24 h at room temperature.
The precipitate was filtered off. On removing the solvents
we isolated from the filtrate 19.8 g (72%) of compound
1
II. H NMR spectrum (CDCl3), d, ppm: 7.81 d (4H),
7.36 d (4H), 4.15 t (4H), 3.67 t (4H), 3.55 s (4H), 2.47 s
(6H).
1,10-Phenanthroline-5,6-dione (IV) was prepared
byproceduredescribedin[4].Acooledmixtureof40ml
of concn. H2SO4 and 20 ml of concn. HNO3 was added
to 4 g (0.022 mol) of 1,10-phenanthroline and 4 g
(0.033 mol) of KBr. The mixture was stirred at 130°C
for 3 h, then the hot yellow solution was poured into
500 ml of ice and cautiously neutralized with NaOH
solution. The separated precipitate of 1,10-phenanthroline-
5,6-dione was filtered off, washed with distilled water,
The crown derivatives of 2,2'-bipyridyl were first
synthesized in 1979 [2]. Later a synthesis was proposed
of bipyridyl-crowns with a carbonyl group included into
the conjugation chain [3].
The preparation of the crown derivatives of 2,2'-bi-
pyridyl and 1,10-phenanthroline is a multistage process.
The common stage of the syntheses is the production of
ditosylate II of the corresponding glycol I which
1070-4280/05/4111-1690Ó2005 Pleiades Publishing, Inc.

SYNTHESIS OF BIFUNCTIONAL LIGANDS BASED ON AZAHETEROCYCLES
1691
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and dried. The rest of the product was extracted with
CH2Cl2 (3´100 ml) from the water phase, and then the
solvent was distilled off. Overall yield 4.5 g (96%).
1H NMR spectrum (CDCl3), d, ppm: 9.15 d.d (2H),
8.53 d.d (2H), 7.62 d.d (2H).
1,10-Phenanthroline-5,6-diol (V). In keeping with
procedure described in [5] a solution of 4.4 g (0.021 mol)
of compound IV in 100 ml of distilled water heated on
a water bath was treated with a solution of hydrazine
hydrochloride till the end of gas evolution. The obtained
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

DENISOVAet al.
1692
water-soluble salt form of 1,10-phenanthroline-5,6-diol
was precipitated by a careful addition of a concn. solution
of NaOH (till pH 5–6). The yellow precipitate was filtered
off,washed with water, and dried. Yield 3.7 g (83%).
1H NMR spectrum (DMSO-d6), d, ppm: 9.40 s (2H),
8.94 d.d (2H), 8.62 d.d (2H), 7.74 m (2H).
(0.02 mol) of acid VII. The solution was cooled for
10 min on an ice bath to 0°C, and 3.2 ml (0.04 mol) of
methyl chloroformate was added dropwise within 30 min.
The mixture was stirred for 1 h. On distilling off the
methanol the separated colorless precipitate was dissolv-
ed in 100 ml of CH2Cl2. The solution was washed with
a saturated solution of sodium hydrogen carbonate
(2´10 ml). On removing the solvent compound VIII was
2,3,5,6,8,9-Hexahydro[1,4,7,10]tetraoxacyclo-
dodecino[2,3-f][1,10]phenanthroline (VI). In 180 ml
of freshly distilled DMF was stirred for 10 min in a flow
of N2 a mixture of 6.4 g (0.014 mol) of triethylene glycol
ditosylate and 46 g (0.141 mol) of cesium carbonate; then
2.7 g (0.0127 mol) of 1,10-phenanthroline-5,6-diol was
added. The reaction mixture was stirred at 60°C under
a nitrogen atmosphere for 5 days. The precipitate was
filtered off and washed with CH2Cl2. The solvents were
distilled off from the combined organic solutions. The
mixture of the reaction products was separated by column
chromatography on aluminum oxide, eluent CH2Cl2. We
obtained 0.629 g (14%) of 1,10-phenanthroline-12-crown-
1
obtained in a 4.13 g (76%) yield. H NMR spectrum
(CDCl3), d, ppm: 8.79 d.d (2H), 8.39 d.d (2H), 7.47 d.d
(2H), 3.71 s (6H).
2,2'-Bipyridyl-3,3'-dimethanol (IX). In 255 ml of
freshly distilled THF under the nitrogen atmosphere was
dissolved 2.56 g (0.0094 mol) of ester VIII. The solution
was cooled for 10 min on an ice bath. A suspension of
sodium bis(2-methoxyethoxy)alumohydride in toluene
containing 0.041 mol of the reductant was dissolved in
39 ml of THF and added dropwise to the reaction mixture.
After stirring for 1 h at 0°C the unreacted reductant was
decomposed by cautious adding water solution of NH4Cl.
The solution was decanted, the precipitate was washed
with 50 ml of CH2Cl2. The organic solutions were
combined, and the solvents were distilled off. The
separated precipitate was washed with ethyl acetate and
filtered off. We obtained 1.2 g (59%) of compound IX.
1H NMR spectrum (CDCl3), d, ppm: 8.51 d.d (2H),
8.04 d.d (2H), 7.47 d.d (2H), 5.30 s (2H), 4.39 s (4H).
1
4, colorless rhombic crystals. H NMR spectrum
(CDCl3), d, ppm: 9.96 d.d (2H), 8.58 d.d (2H), 7.67 m
(2H), 4.48 m (4H), 3.93 s (4H). 13C NMR spectrum
(CDCl3), d, ppm: 150, 145, 143, 131, 126, 123, 78, 74, 72.
Found, %: C 65.99; H 5.30; N 8.41. C18H18N2O4.
Calculated, %: C 66.26; H 5.52; N 8.59. M 326.
2,2'-Bipyridyl-3,3'-dicarboxylic acid (VII). The
oxidation of 1,10-phenanthroline (III) to 2,2'-bipyridyl-
3,3'-dicaboxylic acid (VII) was carried out by procedure
[6]. Into 1 l of water containing 4.4 g (0.11 mol) of NaOH
was charged 10.9 g (0.055 mol) of 1,10-phenanthro-
line·H2O. In the course of stirring at room temperature
was added within 2 h 24.2 g (0.153 mol) of potassium
permanganate. Then the solution was stirred for 2 h at
heating. The hot mixture was filtered from MnO2 and
evaporated to a volume of 100 ml. In distinction from the
procedure [6] the solution was neutralized and compound
VII was converted from the salt into an acid form on a
chromatographic column packed with cation-exchange
resin KU-2·8 in the H+-form. At the output of the column
we obtained a water solution of 2,2'-bipyridyl-3,3'-
dicarboxylic acid. The acid low soluble in water was
partially detained in the column and was separated from
the grains of resin by decanting. On evaporation of water
and decanting we obtained 8.2 g (61.1%) of white
9,11,12,14,15,17,18,20-Octahydropyrido-
[2',3':14,15][1,4,7,10]tetraoxacyclohexadecino-
[13,12-b]pyridine (2,2'-bipyridyl-12-crown-4) (X).
A solution of 1.27 g (0.0059 mol) of diol IX in 200 ml of
anhydrous THF was stirred with 2 g (0.05 mol) of 60%
suspension of NaH in mineral oil for 20 h at 70°C under
the nitrogen atmosphere. To the reaction mixture cooled
to room temperature was added dropwise within 4 h
a solution of 3.12 g (0.0068 mol) of triethylene glycol
ditosylate in 60 ml of anhydrous THF. The reaction
mixture was boiled for 16 h. The precipitate was filtered
off, the solvent was distilled off. To the remaining 20 ml
of the solution 5 ml of H2O was added. The mixture was
dissolved in 150 ml of CH2Cl2 and washed with 1 N HCl
(3´50 ml). The combined water solutions were
neutralized with a concn. solution of NaOH and extracted
with CH2Cl2 (3´100 ml). The combined organic solutions
were evaporated to a volume of 20 ml and subjected to
chromatography on a column packed with aluminum oxide
(eluent acetone–CH2Cl2, 3:7). We obtained 0.508 g
(40%) of powdery 2,2'-bipyridyl-12-crown-4. 1H NMR
spectrum (CDCl3), d, ppm: 8.57 d.d (2H), 7.96 d.d (2H),
7.35 d.d (2H), 4.53 d.d (4H), 3.58 m (8H), 3.34 m (4H).
1
powdery substance. H NMR spectrum (CDCl3), d, ppm:
12.93 s (2H), 8.68 d.d (2H), 8.27 d.d (2H), 7.54 d.d (2H).
Dimethyl 2,2'-bipyridyl-3,3'-dicarboxylate (VIII).
In 150 ml of freshly distilled methanol containing 4.5 ml
(0.04 mol) of N-methylmorpholine was dissolved 4.9 g
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

SYNTHESIS OF BIFUNCTIONAL LIGANDS BASED ON AZAHETEROCYCLES
1693
Found, %: C 65.50; H 6.75; N 8.34. C18H22N2O4.
Calculated, %: C 65.45; H 6.67; N 8.48. M 330.
the reaction products were subjected to column chromato-
graphy on aluminum oxide (eluent CH2Cl2). On evaporat-
ing the solvent we obtained 1.1 g (24%) of colorless
powdery dioxobipyridyl-12-crown-4. 1H NMR spectrum
(CDCl3), d, ppm: 8.80 d.d (2H), 8.53 d.d (2H), 7.49 d.d
(2H), 4.26 m (4H), 3.55 m (8H). Found, %: C 61.11;
H 5.06; N 7.65. C18H18N2O6. Calculated, %: C 60.33;
H 5.03; N 7.82. M 358.
9,10,11,12,14,15,18,19-Decahydrodipyrido[3,2-i:
2,3-k][1,4,7,14]dioxadiazacyclohexadecine-9,20-
dione (XI). To 1.46 g (0.006 mol) of acid VIII in 40 ml
of water was added 0.9 ml (0.006 mol) of 3,6-dioxa-
octane-1,8-diamine. The clear solution containing com-
pound XI was evaporated on a water bath till a volume
of 5 ml. The reaction product was precipitated by adding
20 ml of CH3CN.After stirring for 40 min from the organic
phase a colorless precipitate separated that was filtered
off and washed with ethanol. We obtained 1 g (42%) of
The study was carried out under financial support of
the Russian Foundation for Basic Research (grant
no. 05-03-33256).
1
solvate C16H20N4O4·C2H5OH. H NMR spectrum
REFERENCES
(D2O), d, ppm: 8.44 d.d (2H), 8.03 d.d (2H), 7.43 d.d
(2H), 3.65 m (8H), 3.07 m (4H). 13C NMR spectrum
(D2O), d, ppm: 148.7, 138.1 123.8, 69.9, 66.8, 39.4. Found,
%: C 52.90; H 6.45; N 13.38. C18H26N4O5. Calculated,
%: C 53.73; H 6,47; N 13.93. M 402.
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RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005