The syntheses of nitrogen-oxygen donor macrocycles containing pyridine ring

Article abstract of DOI:10.1002/jhet.5570380341

Five new nitrogen-oxygen mixed donor macrocycles have been prepared by condensation of 2,6-bis [(2-formylphenyl)oxymethyl]pyridine with different diamino compounds in hot methanol, followed by a one-pot reduction of the intermediate bis-Schiff base. All the macrocycles were identified by elemental analysis, and ir, uv, and nmr spectroscopy.

Full text of DOI:10.1002/jhet.5570380341

May-Jun 2001
The Syntheses of Nitrogen-Oxygen Donor
Macrocycles Containing Pyridine Ring
Bin Zhao*, Feng Qin Wang and Lai Jin Tian
781
Department of Chemistry, Qufu Normal University, Qufu 273165, P. R.China
Received November 8, 2000
Five new nitrogen-oxygen mixed donor macrocycles have been prepared by condensation of 2,6-bis
[(2-formylphenyl)oxymethyl]pyridine with different diamino compounds in hot methanol, followed by a
one-pot reduction of the intermediate bis-Schiff base. All the macrocycles were identified by elemental
analysis, and ir, uv, and nmr spectroscopy.
J. Heterocyclic Chem., 38, 781 (2001).
Introduction.
the five new macrocycles containing pyridine ring and
secondary amine functions is shown in Scheme 1. We plan
to study the complexation properties and their transport of
cations. This paper only describes the synthesis of these
compounds.
There is great interest in macrocyclic host ligands
capable of selective recognition of metal cations, anions
and neutral molecules[1]. Oxygen donor macrocycles such
as crown ethers are well known to make strong
complexation with alkali and alkaline earth ions. On the
other hand, polyazamacrocycles show a high affinity for
transition metal ions. Nitrogen-oxygen mixed donor
macrocycles can form stable complexes with both alkali
and transition metal ions. Therefore, mixed donor
macrocycles have received much attention as receptors for
a range of metal ions and other cations [2-5]. Most of the
macrocycles with mixed donor sites bearing oxygen and
Results and Discussion.
The dialdehyde, 2,6-bis[(2-formylphenyl)oxymethyl]-
pyridine, which was used for the final ring closure steps in
the preparation of the macrocycles was obtained by the
reaction of 2,6-ditosyloxymethylpyridine with salicylalde-
hyde in the presence of potassium carbonate in dimethyl-
formamide under nitrogen. A little excess of salicylalde-
hyde was used in order to ensure the formation of the
dialdehyde.
In the syntheses of 5a-5e, the dialdehyde was condensed
with diamines in hot methanol. The corresponding
Schiff-base derivatives were not isolated but instead
reduction was carried out in situ by slow addition of
sodium borohydride to the reaction solution. The
3
2
sp nitrogen atoms, oxygen and sp nitrogen atoms, or
3
2
oxygen and sp and sp nitrogen atoms have shown very
interesting behavior in metal ion discrimination.
In this paper, five new nitrogen-oxygen donor macro-
cycles incorporating sp and sp nitrogen atoms were
synthesized in six steps from commercially available
starting materials. The synthetic route for the synthesis of
2
3

782
B. Zhao, F. Q. Wang and L. J. Tian
Vol. 38
condensation reaction can be performed at room
temperature with a long period of time, but the yields are
usually low. The reduction step can also be carried out at
room temperature without lowering the yields of macro-
cycles. It is not necessary to carry out the ring closure step
under high dilution conditions or in the presence of
template ions.
The structures proposed for the new macrocycles 5a-5e
are consistent with data obtained from their elemental
analyses, and ir, uv, and nmr spectra.
to the stirred solution, and then the mixture was stirred for
3
hours. The reaction solution was filtered and reduced to a small
volume on a rotary evaporator. The residue was dissolved in
water (60 ml), and extracted with chloroform (3 x 50 ml). The
chloroform extracts were mixed and washed with water, dried
over anhydrous sodium sulphate and then evaporated to dryness
to afford a crude oily product, which eventually crystallized to
form a white solid. Recrystallization from ether gave 1.05 g
(70%) of 5a, mp 138-140°; ir: 3480, 3300 (N-H); 2900 (C-H);
1
610 (Py); 1310, 1140 (C-N-C); 1258, 1080 (Ar-O-C); 860
1
(2,6-Py); 760 (1,2-Ar); H nmr: δ 2.66 (s, 2H, NH), 2.78 (s, 4H,
NCH CH ), 3.85 (s, 4H, ArCH ), 5.16 (s, 4H, OCH ), 6.89-7.35
2
2
2
2
(
m, 8H, ArH), 7.37-7.78 (m, 3H,PyH); uv: 286, 317 nm.
EXPERIMENTAL
Anal. Calcd. for C H N O : C, 73.57; H 6.71; N, 11.19.
2
3 25 3 2
Found: C, 72.98; H, 6.75; N, 11.30.
x
Melting points were measured on an XT4-100 A and X
4
microscopic apparatus and are uncorrected. Elemental analyses
were determined on a PE-2400 (II) Elemental Analyser. Ir spectra
were recorded on an IR-810 Spectrophotometer as potassium
bromide pellets. H nmr and C nmr spectra were recorded on a
DPX-400 spectrometer in deuterated chloroform. Chemical shift
Preparation of Macrocycles 5b-5e.
5
b-5e were prepared in a similar manner to the procedure
described above for 5a.
1
13
Compound 5b was obtained in 72% yield (white crystals,
recrystallized from dichloromethane–ether); mp 128-130°; ir:
(δ) are given in ppm relative to that of chloroform (δ = 7.24ppm).
Uv-vis spectra were measured on a WFZ900-D4 spectro-
photometer.
All solvents were of analytical grade and used without further
purification. Ethylene diamine, 1,3-diaminopropane,
3
420, 3254 (N-H); 2900 (C-H); 1610 (Py); 1305, 1120 (C-N-C);
1
1
250, 1080 (Ar-O-C); 860 (2,6-Py); 755 (1,2-Ar). H nmr: δ 1.77
(t, 2H, CCH C); 2.13 (br, 2H, NH), 2.74 (t, 4H, NCH ); 3.82 (s,
2
2
4
7
1
H, ArCH ); 5.06 (s, 4H, OCH ); 6.85-7.27 (m, 8H, ArH);
2 2
1,4-diaminobutane, 1,6-diaminohexane, diethylenetriamine were
13
.35-7.66 (m, 3H, PyH); C nmr: δ 156.13, 137.61, 128.40 (Py);
purified by normal distillation or by distillation under reduced
pressure before use. Starting materials were purchased from
commercial sources where available.
57.18, 130.09, 128.27, 120.99, 119.55, 111.29 (Ar); 69.92
(OCH ); 49.61 (ArCH ); 48.29 (NHCH ); 29.84 (CH ); uv: 288,
2
2
2
2
3
17 nm.
2
,6-Ditosyloxymethylpyridine was prepared from 2,6-
Anal. Calcd. for C H N O : C, 74.00; H, 6.99; N, 10.79.
2
4 27 3 2
bis(hydroxymethyl)pyridine[6] according to the literature
method[7,8].
Found: C, 73.59; H, 7.08; N, 10.62.
Compound 5c was obtained in 68% yield (recrystallized from
ether); mp 63-65°; ir: 3420, 3250 (N-H); 2900, 2827 (C-H); 1605
Preparation of 2,6-Bis[(2-formylphenyl)oxymethyl]pyridine (4)
(
7
Py); 1300, 1130 (C-N-C); 1250, 1060 (Ar-O-C); 860 (2,6-Py);
60 (1,2-Ar); H nmr: δ 1.22 (m, 4H, CH CH ); 2.39
(Scheme 1).
1
2
2
Salicylaldehyde 3 (8.5 g, 0.07 mole), 11g of potassium
(br, 2H, NH); 2.62 (t, 4H, NCH ), 3.73 (s, 4H, ArCH ); 5.16
2 2
carbonate and 80 ml of dimethylformamide were placed in a
three-necked flask. The mixture was warmed to 80° under
nitrogen, and then 13.4 g of 2,6-ditosyloxymethylpyridine (2)
was added. The reaction mixture was stirred vigorously at 80° for
(s, 4H, OCH ); 6.92-7.30 (m, 8H, ArH); 7.50-7.87 (m, 3H, PyH);
2
13C nmr: δ 156.12, 137.86, 128.60 (Py); 157.18, 130.90, 123.00,
121.24, 111.87 (Ar), 71.59 (OCH ), 50.22 (ArCH ), 48.47
2
2
(NHCH ), 26.95 (CH ); uv: 290, 317 nm.
2
2
10 hours. After cooling, the reaction mixture was poured into ice-
Anal. Calcd for C H N O : C, 74.41; H, 7.24; N, 10.42.
25 29 3 2
water (200 ml). The pale yellow solid was filtered, washed with
water and dried. The crude product was decolored by active
carbon and recrystallized from methanol to give 9.11 g (75%) of
white crystals of dialdehyde 4, mp 136-138°; ir: 2850 (C-H),
Found: C, 74.20; H, 7.09; N, 9.98.
Compound 5d was obtained in 74% yield (recrystallized from
ether); mp 72-76°; ir: 3425 (N-H); 2920, 2848 (C-H); 1610 (Py);
1310, 1138 (C-N-C); 1258, 1062 (Ar-O-C); 866 (2,6-Py); 766
1
1
700 (CHO), 1252, 1080 (Ar-O-C), 1611 (Py), 862 (1,3-Py), 760
(1,2-Ar); H nmr: δ 0.90-1.24 (m, 8H, CH ); 2.13 (s, 2H, NH);
2
1
(
7
(
1,2-Ar); H nmr: δ 10.62 (s, 2H, CHO); 7.60-7.88 (m, 3H, PyH);
2.60 (t, 4H, NCH ); 3.80 (s, 4H,ArCH ); 5.20 (s, 4H, OCH );
2
2
2
1
3
.09-7.56 (m, 8H, ArH); 5.36 (s, 4H, OCH2); C nmr: δ 189.56
6.95-7.32 (m, 8H, ArH); 7.57-7.90 (m, 3H, PyH); uv: 286, 315
nm.
CHO); 155.97, 138.20, 128.98 (Py); 160.42, 136.01, 125.03,
21.36, 120.53, 112.87 (Ar); 70.75 (OCH2).
Anal. Calcd. for C21H17NO : C, 72.61; H, 4.93; N, 4.03.
1
Anal. Calcd. for C H N O : C, 75.14; H, 7.70; N, 9.74.
27 33 3 2
Found: C, 75.21; H, 7.78; N, 9.87.
4
Found: C, 72.60; H, 4.92; N, 4.01.
Compound 5e was obtained in 65% as an oil; ir: 3420
(
1
br, N-H); 2920, 2835 (C-H); 1611 (Py); 1310,1136 (C-N-C);
257,1064 (Ar-O-C); 860 (2,6-Py); 760 (1,2-Ar); H nmr: δ 2.54
Preparation of Macrocycles 5a.
1
To a refluxing solution of dialdehyde 4 (1.40 g, 0.004 mole) in
(s, 3H, NH); 2.64-2.70 (m, 8H, NCH ); 3.76 (s, 4H, ArCH );
2 2
1
50 ml of methanol was added 0.24 g (0.004 mole) of ethyl-
5.19 (s, 4H, OCH ); 6.95-7.28 (m, 8H, ArH); 7.46-7.83 (m, 3H,
2
enediamine in 50 ml of methanol. After the addition, the reaction
solution was stirred for 5 minutes, and then a small amount of
borax followed by sodium borohydride (0.8 g) were added slowly
PyH); uv: 291 nm.
Anal. Calcd. for C H N O : C, 71.74; H, 7.22; N, 13.39.
Found: C, 71.62; H, 7.36; N, 13.51.
2
5 30 4 2

May-Jun 2001
The Syntheses of Nitrogen-Oxygen Donor Macrocycles Containing Pyridine Ring
783
Acknowledgement.
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(
We are grateful to the Natural Science Foundation of
Shandong Province for financial support of this work
[
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