Synthesis of expanded alkylphenoxythiadiazole macroheterocycles

Article abstract of DOI:10.1016/j.mencom.2008.09.022

New substituted macroheterocyclic compounds of the ABABAB type were synthesised by condensation of 2,5-diamino-1,3,4-thiadiazole with the products of interaction of 4-(4-tert-butylphenoxy)- or 4-(3,5-dimethylphenoxy)phthalonitriles with sodium alkoxides i

Full text of DOI:10.1016/j.mencom.2008.09.022

Mendeleev
Communications
Mendeleev Commun., 2008, 18, 289–290
Synthesis of expanded alkylphenoxythiadiazole macroheterocycles
Natalia V. Bumbina,a Elena A. Danilova,a Vladimir S. Sharunov,b
Sergei I. Filimonov,b Igor G. Abramovb and Mikhail K. Islyaikin*a
a Department of Fine Organic Synthesis, Ivanovo State University of Chemistry and Technology, 153000 Ivanovo,
Russian Federation. Fax: + 7 4932 41 7742; e-mail: islyaikin@isuct.ru
b
Yaroslavl State Technical University, 150023 Yaroslavl, Russian Federation. Fax: + 7 4852 44 6525;
e-mail:abramovig@ystu.ru
DOI: 10.1016/j.mencom.2008.09.022
New substituted macroheterocyclic compounds of the ABABAB type were synthesised by condensation of 2,5-diamino-
1,3,4-thiadiazole with the products of interaction of 4-(4-tert-butylphenoxy)- or 4-(3,5-dimethylphenoxy)phthalonitriles with
sodium alkoxides in a butanol–methanol mixture.
Macroheterocyclic compounds of the ABABAB type consist of
three 1,3,4-thiadiazole rings (A) and three isoindole subunits (B)
connected to each other via aza bridges.1–3 They belong to a
new class of porphyrinoids having an expanded coordination
cavity and can be considered as heteroanalogues of hexaphyrins.4
At the same time, these compounds can be considered as expanded
hemiporphyrazines,5 more exactly, triazolehemiporphyrazines.6,7
However, they are different from expanded ABBABB system
discovered recently.8 The coordinating properties and acid-basic
behaviours of ABABAB-type compounds have been published
recently.9–11
carbonate, took place. The synthesis of 4-(4-tert-butylphenoxy)-
phthalonitrile 1 and 4-(3,5-dimethylphenoxy)phthalonitrile 2
was described elsewhere.12,† 2,5-Diamino-1,3,4-thiadiazole was
synthesised according to the procedure described previously.13
Macroheterocyclic compounds 3, 4 were synthesised by con-
densation of 2,5-diamino-1,3,4-thiadiazole with the products of
interaction of 4-(4-tert-butyl)phthalonitrile 1 or 4-(3,5-dimethoxy)-
phthalonitrile 2 with sodium alkoxides in butanol–methanol
(Scheme 1).‡,§
The reaction run has been monitored by TLC and UV-VIS
spectroscopy. Compounds 3, 4 were purified by column chromato-
graphy on aluminium oxide using dichloromethane as an eluent.
Compounds 3, 4 were characterised by UV-VIS, IR and
1H NMR spectroscopy, mass spectrometry and elemental analysis.§
Here, we report on the synthesis and spectral characteriza-
tion of new substituted macroheterocyclic compounds of the
ABABAB type.
4-Aryloxyphthalonitriles 1, 2 were synthesised using the SNAr
reaction of 4-nitrophthalonitrile with corresponding phenols in
the presence of K2CO3 in aqueous DMF (75%). A substitution
of the nitro group by [O–]-nucleophiles, which have been
generated in situ from corresponding phenols and potassium
†
4-(4-tert-Butylphenoxy)phthalonitrile 1. A solution of K2CO3 (1.56 g,
0.01 mol) in water (10 ml) was added under strong agitation into a
solution containing 4-nitrophthalonitrile (1.73 g, 0.01 mol), 4-tert-butyl-
phenol (1.50 g, 0.01 mol) and DMF (30 ml). The reaction mixture
was very intensely agitated at 80–95 °C for 1 h. After cooling to room
temperature, the reaction mixture was poured into water (100 ml), the
precipitate was filtered, washed with water (50 ml) and recrystallised
from propan-2-ol. The yield of compound 1 was 2.05 g (74%) as a white
R
crystalline powder, mp 118–119 °C. H NMR ([2H6]DMSO) d: 8.03 (d,
1
1H, 6-H, J 8.8 Hz), 7.61 (d, 1H, 3-H, J 2.5 Hz), 7.48 (d, 2H, 3'-H, 5'-H,
J 8.5 Hz), 7.32 (dd, 1H, 5-H, J 2.5 Hz, J 8.8 Hz), 7.05 (d, 2H, 2'-H, 6'-H,
J 8.5 Hz), 1.33 (s, 9H, But). Found (%): C, 78.56; H, 5.91; N, 10.05.
Calc. for C18H16N2O (%): C, 78.24; H, 5.84; N, 10.14.
NH2
N
N
N
S
N
N
H
S
S
NH2
N
N
4-(3,5-Dimethylphenoxy)phthalonitrile 2 was synthesised using equi-
molar quantity of 3,5-xylenol. The yield of compound 2 was 1.87 g (75%)
R
CN
CN
i, ii
N
N
N
N
1
as a white crystalline powder, mp 115–116 °C. H NMR ([2H6]DMSO)
HN
NH
d: 8.02 (d, 1H, 6-H, J 8.8 Hz), 7.59 (d, 1H, 3-H, J 2.4 Hz), 7.32 (dd, 1H,
5-H, J 2.4 Hz, J 8.8 Hz), 6.92 (s, 1H, 4'-H), 6.73 (s, 2H, 2'-H, 6'-H), 2.31
(s, 6H, Me). Found (%): C, 77.65; H, 4.98; N, 11.11. Calc. for C16H12N2O
(%): C, 77.40; H, 4.87; N, 11.28.
N
N
1, 2
R
R
N
N
S
3, 4
‡
Compounds 3, 4 were synthesised according to a general procedure:
metallic sodium (0.267 mmol) was dissolved in a mixture of butanol
(5 ml) and methanol (0.2 ml). Then dinitrile 1 or 2 (0.181 mmol) was
added to this solution, and the reaction mixture was stirred for 7 h at
room temperature. After addition of ammonium chloride (0.267 mmol),
the reaction mass was stirred for 3 h. Finally, 2,5-diamino-1,3,4-thia-
diazole (0.181 mmol) was added and the reaction mixture was stirred at
80 °C for 2 h and after that at reflux for 33 h. After the solvents were
removed, a solid was treated with methanol and a precipitate was separated
by filtration, washed with MeOH, and dried. Purification was made using
column chromatography on aluminium oxide; eluent, dichloromethane.
After solvent removal, the orange solid was washed with MeOH and
dried in a vacuum.
But
1, 3 R =
2, 4 R =
O
Me
O
Me
Scheme 1 Reagents and conditions: i, MeONa, BuONa, MeOH, BuOH,
7 h, 20–25 °C; ii, NH4Cl, 3 h, 20–25 °C, 2,5-diamino-1,3,4-thiadiazole,
33 h, 120 °C.
– 289 –
© 2008 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2008, 18, 289–290
of both compounds while the bands of lower intensities are
415
416
(a)
(b)
396
395
located at about 450–505 nm. These spectra are similar to the
spectrum of tert-butyl-substituted macroheterocyclic compound
of ABABAB type,1,2 and it can evidence the similarity of their
chromophore systems.
Mass spectra of compounds 3 and 4 are characterised by the
presence of peaks corresponding to the molecular ions [M + H]+.
A perfect coincidence of molecular mass as well as the isotope
distributions and calculated values proofs the structures of these
compounds as macrocyclic systems of the ABABAB type
containing three 1,3,4-thiadiazole rings and three substituted
isoindole subunits.
0.8
0.6
0.4
0.2
0.0
0.6
0.4
0.2
0.0
467
465
503
502
400
500
600
400
500
600
l/nm
l/nm
Figure 1 UV-VIS spectra of macroheterocycles in CH2Cl2: (a) 3 (C =
= 3.30 mol dm–3); (b) 4 (C = 3.80 mol dm–3).
1H NMR spectra of compounds 3 and 4, measured in CDCl3,
reveal the signals at 1.37 and 1.25 ppm, respectively, which can
be assigned to the protons of alkyl groups. The multiplets at
7.79–7.02 (3) and 7.78–7.25 ppm (4) are due to the resonance
of the protons of benzene rings, and the singlets at 12.27 (3) and
12.36 ppm (4) characterise the absorbance of the protons of
imino groups. The presence of these signals in the low field
highlights the non-aromatic character of ABABAB macrocycle.
The IR spectra of compounds 3 and 4 are similar to each
other. Thus, in the spectrum of compound 3, a series of bands at
2959, 2918 and 2849 cm–1 characterises the C–H stretching
vibrations of tert-butyl groups. The band at 3217 cm–1 is induced
by N–H vibrations of imino groups. The strong bands at 2916
and 2848 cm–1 in the spectrum of 4 can be assigned to C–H
vibrations of methyl groups. The absorption band corresponding
to N–H stretching vibrations of imino groups is observed at
3212 cm–1.
References
The UV-VIS spectra of compounds 3 and 4 shown in Figure 1
are similar. Thus, the strong absorbance bands at 396 and
415 nm (3) and at 395 and 416 nm (4) dominate in the spectra
1
2
3
4
5
6
M. K. Islyaikin, E. A. Danilova, L. D. Yagodarova, S. M. Rodríguez-
Morgade and T. Torres, Org. Lett., 2001, 3, 2153.
N. Kobayashi, S. Inagaki, V. N. Nemykin and T. Nonomura, Angew.
Chem., Int. Ed. Engl., 2001, 40, 2710.
M. K. Islyaikin, E. A. Danilova and L. D. Yagodarova, Izv. Vuz. Khim.
Khim. Tekhnol., 2003, 46, 3 (in Russian).
J. L. Sessler and D. Seidel, Angew. Chem., Int. Ed. Engl., 2003, 42,
5134.
F. Fernández-Lázaro, T. Torres, B. Hauschel and M. Hanack, Chem.
§
2,14(15),26(27)-Tri(4-tert-butylphenoxy)-5,36:12,17:24,29-triimino-
7,10:19,22:31,34-trithia-[f,p,z]-tribenzo-1,2,4,9,11,12,14,19,21,22,24,29-
dodecazacyclotriaconta-2,4,6,8,10,12,14,16,18,20,22,24,26,28,30-penta-
decaene 3 was obtained following general procedure from 4-(4-tert-butyl-
phenoxy)phthalonitrile (50 mg, 0.181 mmol) and 2,5-diamino-1,3,4-thia-
diazole (21 mg, 0.181 mmol). Yield, 15 mg (22%). UV-VIS [CH2Cl2,
Rev., 1998, 98, 563.
l
max/nm (log e)]: 396 (4.92), 415 (4.94), 467 (sh), 503 (4.21). IR (thin
F. Fernández-Lázaro, J. de Mendoza, O. Mó, S. Rodríguez-Morgade,
T. Torres, M. Yànez and J. Elguero, J. Chem. Soc., Perkin Trans. 2,
1989, 797.
film, n/cm–1): 3217, 2959, 2918, 2849, 1629, 1508, 1478, 1407, 1367,
1327, 1272, 1235, 1214, 1101, 1032, 928, 837, 716. 1H NMR (CDCl3) d:
12.27 (s, NH), 7.79, 7.40, 7.13, 7.02 (m, H arom.), 1.37 (s, CMe). Found
(%): C, 62.46; H, 4.31; N, 17.51; S, 7.59. Calc. for C60H51N15O3S3 (%):
C, 63.98; H, 4.56; N, 18.65; S, 8.54. MS (MALDI-TOF), m/z: 1126
[M + H]+.
7
8
G. de la Torre and T. Torres, J. Org. Chem., 1996, 61, 6446.
M. S. Rodríguez-Morgade, B. Cabezón, S. Esperanza and T. Torres,
Chem. Eur. J., 2001, 7, 2407.
9
M. K. Islyaikin, O. G. Khelevina, T. N. Lomova and E. A. Danilova,
Izv. Vuz. Khim. Khim. Tekhnol., 2004, 47, 35 (in Russian).
2,14(15),26(27)-Tri(3,5-dimethylphenoxy)-5,36:12,17:24,29-triimino-
7,10:19,22:31,34-trithia-[f,p,z]-tribenzo-1,2,4,9,11,12,14,19,21,22,24,29-
dodecazacyclotriaconte-2,4,6,8,10,12,14,16,18,20,22,24,26,28,30-penta-
decaene 4 was obtained following general procedure from 4-(3,5-dimethyl-
phenoxy)phthalonitrile (45 mg, 0.181 mmol) and 2,5-diamino-1,3,4-thia-
diazole (21 mg, 0.181 mmol). Yield, 14 mg (20%). UV-VIS [CH2Cl2,
10 T. N. Lomova, E. E. Suslova, E. A. Danilova and M. K. Islyaikin, Zh.
Fiz. Khim., 2005, 79, 263 (Russ. J. Phys. Chem., 2005, 79, 201).
11 T. N. Lomova, E. G. Mozhzhukhina, E. A. Danilova and M. K. Islyaikin,
Koord. Khim., 2006, 32, 869 (Russ. J. Coord. Chem., 2006, 32, 837).
12 V. V. Plakhtinsky, P. S. Kaninsky, G. S. Mironov, O. A. Yasinsky and
I. G. Abramov, Zh. Org. Khim., 1992, 28, 1232 (in Russian).
13 E. A. Danilova, M. K. Islyaikin, N. A. Kolesnikov and T. V. Melenchuk,
RF Patent, 2313518, 2007.
l
max/nm (log e)]: 395 (4.95), 416 (4.97), 465 (sh), 502 (4.23). IR (thin
film, n/cm–1): 3212, 2916, 2849, 1615, 1478, 1406, 1368, 1326, 1294,
1272, 1226, 1200, 1136, 1100, 1033, 950, 834, 741, 716. 1H NMR (CDCl3)
d: 12.36 (s, NH), 7.78, 7.39, 7.25 (m, H arom.), 1.25 (s, Me). Found (%):
C, 62.06; H, 3.32; N, 18.42; S, 7.93. Calc. for C54H39N15O3S3 (%): C, 62.23;
H, 3.77; N, 20.16; S, 9.23. MS (MALDI-TOF), m/z: 1042 [M + H]+.
Received: 21st April 2008; Com. 08/3126
– 290 –