Synthesis of functionally substituted isoxazole-containing benzaldehydes of the vanillin series and Schiff bases derived therefrom

Article abstract of DOI:10.1134/S1070428013100199

5-Chloromethyl-3-methyl-1,2-oxazole reacted with benzaldehydes of the vanillin series in the presence of potassium carbonate in boiling ethanol (Williamson reaction) to produce the corresponding isoxazolylmethyloxy- substituted benzaldehydes which were br

Full text of DOI:10.1134/S1070428013100199

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 10, pp. 1517–1522. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © E.A. Dikusar, R.A. Gadzhily, V.I. Potkin, S.K. Petkevich, T.D. Zvereva, A.G. Aliev, L.Ya. Gadzhieva, 2013, published in Zhurnal
Organicheskoi Khimii, 2013, Vol. 49, No. 10, pp. 1537–1542.
Synthesis of Functionally Substituted
Isoxazole-Containing Benzaldehydes of the Vanillin Series
and Schiff Bases Derived Therefrom
E. A. Dikusara, R. A. Gadzhilyb, V. I. Potkina, S. K. Petkevicha, T. D. Zverevaa,
A. G. Alievb, and L. Ya. Gadzhievab
a Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: dikusar@ifoch.bas-net.by
b Institute of Polymeric Materials, National Academy of Sciences of Azerbaijan, Sumgait, Azerbaijan
Received April 15, 2013
Abstract—5-Chloromethyl-3-methyl-1,2-oxazole reacted with benzaldehydes of the vanillin series in the
presence of potassium carbonate in boiling ethanol (Williamson reaction) to produce the corresponding
isoxazolylmethyloxy-substituted benzaldehydes which were brought into condensation with aromatic amines
and diamines in boiling methanol to obtain functionally substituted Schiff bases.
DOI: 10.1134/S1070428013100199
Introduction of pharmacophoric structural frag-
ments into molecules of organic compounds with
a view to endow them with antitumor, antimicrobial,
fungicidal, insecticidal, and nematocidal activity con-
stitutes an important problem of modern pharmaceu-
tical chemistry and agrochemistry [1, 2]. In the present
article we describe the reaction of 5-chloromethyl-3-
methyl-1,2-oxazole (I) [3] with hydroxybenzaldehydes
II–V of the vanillin series [4] in the presence of anhy-
drous potassium carbonate in boiling 96% ethanol
Scheme 1.
Me
Me
CHO
CHO
K2CO3, EtOH
HO
O
+
Cl
N
N
O
R1
R1
VI–IX
O
I
II–V
Me
NR2
R2NH2 (X–XII)
O
N
O
O
R1
XV–XXVI
MeOH
Me
Me
X
N
N
H2N–X–NH2 (XIII, XIV)
O
O
N
N
O
R1
R1
XXVII–XXXIV
II, IV, V, 4-OH; III, 3-OH; II, VI, XV–XVII, XXVII, XXVIII, R1 = H; III, VII, XVIII–XX, XXIX, XXX, R1 = 4-OMe; IV, VIII,
XXI–XXIII, XXXI, XXXII, R1 = 3-OMe, V, IX, XXIV–XXVI, XXXIII, XXXIV, R1 = 3-OEt; X, XV, XVIII, XXI, XXIV, R2 =
4-PhC6H4; XI, XVI, XIX, XXII, XXV, R2 = 4-PhOC6H4, XII, XVII, XX, XXIII, XXVI, R2 = 4-HOC(O)C6H4; XIII, XXVII, XXIX,
XXXI, XXXIII, X = 1,4-C6H4; XIV, XXVIII, XXX, XXXII, XXXIV, X = 4,4′-C6H4C6H4; VI, VIII, IX, XV–XVII, XXI–XXVIII,
XXXI–XXXIV, 4-(3-methyl-1,2-isoxazol-5-ylmethoxy); VII, XVIII–XX, XXIX, XXX, 3-(3-methyl-1,2-isoxazol-5-ylmethoxy).
1517

DIKUSAR et al.
1518
(Williamson ether synthesis) [5], which afforded iso-
xazolylmethyloxy-substituted benzaldehydes VI–IX in
80–96% yield. Aldehydes VI–IX smoothly reacted
with aromatic amines and diamines X–XIV to give
75–89% of functionally substituted isoxazole-contain-
ing Schiff bases XV–XXXIV. The use of an ether
rather than ester bond as linker to build up isoxazole-
containing structures seems to be more advantageous
taking into account possible aminolysis of esters [6, 7].
cm–1: 3128 (CHisox); 3103, 3076, 3015 (CHarom); 2928,
2836, 2810 (CHaliph); 2751 (CHald); 1684 (C=O); 1617,
1602, 1508 (C=Carom); 1424 (C=Nisox); 1245, 1165,
1007 (C–O); 900, 864, 836, 818, 735 (δ CHarom).
1H NMR spectrum, δ, ppm: 2.28 s (3H, Me), 5.18 s
3
(2H, CH2), 6.19 s (1H, 4′-H), 7.04 d (2H, Harom, J =
8 Hz), 7.80 d (2H, Harom, 3J = 8 Hz), 9.87 s (1H, CHO).
13C NMR spectrum, δC, ppm: 11.50 (Me), 61.33 (CH2),
104.54 (C4′), 115.09 (2C, CHarom), 132.11 (2C, CHarom);
130.85, 160.12, 162.65, 166.63 (Cquat); 190.80 (C=O).
Mass spectrum: m/z 217 [M]+. Found, %: C 66.84;
H 5.31; N 6.09. C12H11NO3. Calculated, %: C 66.35;
H 5.10; N 6.45. M 217.22.
Substituted benzaldehydes VI–IX and Schiff bases
XV–XXXIV were isolated as yellow or orange crystal-
line substances which contained no impurities of the
initial compounds and required no additional purifica-
tion. Their structure was confirmed by the data of ele-
4-Methoxy-3-[(3-methyl-1,2-oxazol-5-yl)me-
thoxy]benzaldehyde (VII). Yield 81%, mp 89–90°C.
IR spectrum, ν, cm–1: 3133 (CHisox); 3080, 3065, 3045,
3031, 3009 (CHarom); 2971, 2835, 2900, 2851, 2840
(CHaliph); 2761 (CHald); 1686 (C=O); 1615, 1597, 1583,
1509 (C=Carom); 1436 (C=Nisox); 1267, 1238, 1161,
1128, 1016 (C–O); 887, 831, 815, 805, 765, 740
1
mental analysis and IR and H NMR spectroscopy, as
well as by molecular weight determination. Schiff
bases XV–XXXIV were assigned E configuration at
the azomethine C=N bond by comparing their 1H NMR
spectra with the spectra of structurally related com-
pounds [3, 4, 7] and with the data of [8].
1
(δCHarom). H NMR spectrum, δ, ppm: 2.27 s (3H,
A number of the synthesized compounds containing
pharmacophoric aromatic and heterocyclic fragments
are now tested for biological activity with a view to
reveal structure–activity correlations [9].
Me), 3.93 s (3H, MeO), 5.20 s (2H, CH2), 6.20 s (1H,
4′-H), 6.99 d (1H, Harom, 3J = 8 Hz), 7.44 s (1H, Harom),
3
7.50 d.d (1H, Harom, J = 8 Hz), 9.81 s (1H, CHO).
13C NMR spectrum, δC, ppm: 11.50 (Me), 56.33
(OCH3), 62.19 (CH2), 104.65 (C4′), 111.30 (CHarom),
112.19 (CHarom), 127.71 (CHarom); 130.03, 147.84,
155.18, 159.99, 166.91 (Cquat); 190.66 (C=O). Mass
spectrum: m/z 247 [M]+. Found, %: C 63.59; H 5.45;
N 5.31. C13H13NO4. Calculated, %: C 63.15; H 5.30;
N 5.67. M 247.25.
EXPERIMENTAL
The IR spectra were recorded in KBr on a Nicolet
Protégé-460 spectrometer with Fourier transform. The
1H and 13C NMR spectra were measured on a Bruker
Avance-500 instrument from 5% solutions in CDCl3 or
DMSO-d6. The chemical shifts were determined
relative to the residual proton and carbon signals of the
solvent (CHCl3, δ 7.26 ppm; DMSO-d5, δ 2.50 ppm;
CDCl3, δC 77.2 ppm). The mass spectra (electron
impact, 70 eV) were obtained on a Hewlett Packard
5890/5972 GC/MS system (HP-5MS capillary column,
30 m×0.25 mm, film thickness 0.25 μm, injector tem-
perature 250°C).
Aldehydes VI–IX (general procedure). A mixture
of 10 mmol of 5-chloromethyl-3-methyl-1,2-isoxazole
(I), 10 mmol of hydroxybenzaldehyde II–V, and
5 mmol of anhydrous potassium carbonate in 50 ml of
96% ethanol was heated for 12 h at 70°C under stirring
in a nitrogen atmosphere. The mixture was cooled and
diluted with 100 ml of water, and the precipitate was
filtered off through a glass frit, washed with water, and
dried for 2–3 days at 25–30°C in air.
3-Methoxy-4-[(3-methyl-1,2-oxazol-5-yl)me-
thoxy]benzaldehyde (VIII). Yield 96%, mp 80–81°C.
IR spectrum, ν, cm–1: 3134 (CHisox); 3080, 3064, 3030,
3008 (CHarom); 2974, 2956, 2942, 2883, 2833 (CHaliph);
2762 (CHald); 1677 (C=O); 1624, 1597, 1587, 1507
(C=Carom); 1421 (C=Nisox); 1266, 1231, 1155, 1138,
1018 (C–O); 890, 858, 827, 792, 756, 728 (δCHarom).
1H NMR spectrum, δ, ppm: 2.29 s (3H, Me), 3.93 s
(3H, MeO), 5.27 s (2H, CH2), 6.21 s (1H, 4′-H), 7.03 d
(1H, Harom, 3J = 8 Hz), 7.42 d.d (1H, Harom, 3J = 8 Hz),
7.43 s (1H, Harom), 9.86 s (1H, CHO). 13C NMR spec-
trum, δC, ppm: 11.55 (Me), 56.25 (OCH3), 62.26
(CH2), 104.70 (C4′), 109.96 (CHarom), 112.98 (CHarom),
126.42 (CHarom); 131.42, 150.36, 152.61, 160.19,
166.83 (Cquat); 190.97 (C=O). Mass spectrum: m/z 247
[M]+. Found, %: C 63.46; H 5.21; N 5.23. C13H13NO4.
Calculated, %: C 63.15; H 5.30; N 5.67. M 247.25.
4-[(3-Methyl-1,2-oxazol-5-yl)methoxy]benzalde-
hyde (VI). Yield 80%, mp 105–106°C. IR spectrum, ν,
3-Ethoxy-4-[(3-methyl-1,2-oxazol-5-yl)methoxy]-
benzaldehyde (IX). Yield 95%, mp 77–78°C. IR spec-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 10 2013

SYNTHESIS OF FUNCTIONALLY SUBSTITUTED ISOXAZOLE-CONTAINING
1519
trum, ν, cm–1: 3127 (CHisox); 3080, 3062, 3008
(CHarom); 2979, 2967, 2932, 2843, 2829 (CHaliph); 2763
(CHald); 1677 (C=O); 1616, 1597, 1587, 1508
(C=Carom); 1439 (C=Nisox); 1262, 1231, 1139, 1040,
1008 (C–O); 896, 870, 848, 810, 764, 740, 724
4-{(E)-4-[(3-Methyl-1,2-oxazol-5-yl)methoxy]-
benzylideneamino}benzoic acid (XVII). Yield 89%,
mp 201–202°C. IR spectrum, ν, cm–1: 3145 (CHisox);
3063, 3002 (CHarom); 2970, 2925, 2854 (CHaliph); 1677
(C=O); 1628 (C=N); 1590, 1575, 1513 (C=Carom);
1426 (C=Nisox); 1257, 1164, 1113, 1054 (C–O); 892,
1
(δCHarom). H NMR spectrum, δ, ppm: 1.47 t (3H,
3
1
MeCH2, J = 7 Hz), 2.29 s (3H, Me), 4.15 q (2H,
866, 834, 809, 772, 760 (δCHarom). H NMR spectrum,
3
MeCH2, J = 7 Hz), 5.26 s (2H, CH2), 6.19 s (1H,
δ, ppm: 2.24 s (3H, Me), 5.37 s (2H, CH2), 6.42 s (1H,
4′-H), 6.93–7.94 m (8H, Harom), 8.51 s (1H, CH=N),
9.87 s (1H, CO2H). Mass spectrum: m/z 336 [M]+.
Found, %: C 68.04; H 4.90; N 7.98. C19H16N2O4. Cal-
culated, %: C 67.85; H 4.79; N 8.33. M 336.34.
3
4′-H), 7.00 d (1H, Harom, J = 8 Hz), 7.39 d.d (1H,
H
arom, 3J = 8 Hz), 7.41 s (1H, Harom), 9.84 s (1H, CHO).
13C NMR spectrum, δC, ppm: 11.52 (Me), 14.77
(MeCH2), 62.40 (CH2), 64.72 (MeCH2), 104.49 (C4′),
111.16 (CHarom), 113.53 (CHarom), 126.13 (CHarom);
131.39, 149.69, 152.76, 160.09, 167.02 (Cquat); 191.00
(C=O). Mass spectrum: m/z 261 [M]+. Found, %:
C 64.65; H 5.88; N 5.04. C14H15NO4. Calculated, %:
C 64.36; H 5.79; N 5.36. M 261.27.
N-{(E)-4-Methoxy-3-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylidene}biphenyl-4-amine (XVIII).
Yield 89%, mp 159–160°C. IR spectrum, ν, cm–1: 3130
(CHisox); 3080, 3073, 3034, 3002 (CHarom); 2965, 2924,
2853 (CHaliph); 1629 (C=N); 1607, 1595, 1579, 1513,
1483 (C=Carom); 1433 (C=Nisox); 1269, 1240, 1159,
1136, 1018 (C–O); 889, 865, 840, 811, 764, 741, 694
Schiff bases XV–XXVI (general procedure).
A solution of 5 mmol of aldehyde VI–IX and 5 mmol
of aromatic amine X–XII in 40 ml of anhydrous
methanol was heated for 30–45 min under reflux. The
mixture was cooled to 0–5°C, and the precipitate of
Schiff base XV–XXVI was filtered through a glass
frit, washed with cold methanol, and dried for 6–8 h
in air.
1
(δCHarom). H NMR spectrum, δ, ppm: 2.25 s (3H,
Me), 3.86 s (3H, MeO), 5.28 s (2H, CH2), 6.49 s (1H,
4′-H), 7.03–7.70 m (12H, Harom), 8.54 s (1H, CH=N).
Mass spectrum: m/z 398 [M]+. Found, %: C 75.49;
H 5.70; N 6.72. C25H22N2O3. Calculated, %: C 75.36;
H 5.57; N 7.03. M 398.45.
N-{(E)-[4-(3-Methyl-1,2-oxazol-5-yl)methoxy]-
benzylidene}biphenyl-4-amine (XV). Yield 82%,
mp 195–196°C. IR spectrum, ν, cm–1: 3145 (CHisox);
3080, 3072, 3034, 3002 (CHarom); 2965, 2923, 2910,
2851 (CHaliph); 1626 (C=N); 1608, 1597, 1577, 1508,
1484 (C=Carom); 1424 (C=Nisox); 1251, 1172, 1040,
1053 (C–O); 886, 837, 819, 767, 726, 691 (δCHarom).
1H NMR spectrum, δ, ppm: 2.32 s (3H, Me), 5.19 s
(2H, CH2), 6.19 s (1H, CHisox), 6.90–7.96 m (13H,
Harom), 8.46 s (1H, CH=N). Mass spectrum: m/z 368
[M]+. Found, %: C 78.46; H 5.75; N 7.21. C24H20N2O2.
Calculated, %: C 78.24; H 5.47; N 7.60. M 368.43.
N-{(E)-4-Methoxy-3-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylidene}-4-phenoxyaniline (XIX).
Yield 78%, mp 112–113°C. IR spectrum, ν, cm–1: 3134
(CHisox); 3090, 3076, 3065, 3054, 3035, 3025 (CHarom);
2965, 2940, 2926, 2870, 2845 (CHaliph); 1621 (C=N);
1600, 1591, 1580, 1515, 1499, 1486 (C=Carom); 1431
(C=Nisox); 1264, 1237, 1206, 1167, 1130, 1098, 1018,
1007 (C–O); 898, 865, 830, 824, 810, 771, 696
1
(δCHarom). H NMR spectrum, δ, ppm: 2.31 s (3H,
Me), 3.94 s (3H, MeO), 5.27 s (2H, CH2), 6.22 s (1H,
4′-H), 6.92–7.74 m (12H, Harom), 8.38 s (1H, CH=N).
Mass spectrum: m/z 414 [M]+. Found, %: C 72.84;
H 5.48; N 6.39. C25H22N2O4. Calculated, %: C 72.45;
H 5.35; N 6.76. M 414.45.
N-{(E)-4-[(3-Methyl-1,2-oxazol-5-yl)methoxy]-
benzylidene}-4-phenoxyaniline (XVI). Yield 77%,
mp 119–120°C. IR spectrum, ν, cm–1: 3135 (CHisox);
3082, 3074, 3055, 3040, 3002 (CHarom); 2965, 2924,
2855 (CHaliph); 1623 (C=N); 1606, 1599, 1575, 1510,
1499, 1490 (C=Carom); 1420 (C=Nisox); 1262, 1249,
1164, 1108, 1022, 1006 (C–O); 880, 845, 818, 776,
4-{(E)-4-Methoxy-3-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylideneamino}benzoic acid (XX).
Yield 75%, mp 191–192°C. IR spectrum, ν, cm–1: 3147
(CHisox); 3065, 3052, 3002 (CHarom); 2970, 2923, 2860,
2841 (CHaliph); 1683 (C=O); 1631 (C=N); 1596, 1584,
1520 (C=Carom); 1426 (C=Nisox); 1294, 1272, 1242,
1220, 1168, 1135, 1019 (C–O); 880, 858, 816, 798,
1
740, 691 (δCHarom). H NMR spectrum, δC, ppm:
2.33 s (3H, Me), 5.20 s (2H, CH2), 6.18 s (1H, 4′-H),
6.88–7.93 m (13H, Harom), 8.43 s (1H, CH=N). Mass
spectrum: m/z 384 [M]+. Found, %: C 75.23; H 5.42;
N 7.07. C24H20N2O3. Calculated, %: C 74.98; H 5.24;
N 7.29. M 384.43.
1
775, 703, 658 (δCHarom). H NMR spectrum, δ, ppm:
2.24 s (3H, Me), 3.93 s (3H, MeO), 5.36 s (2H, CH2),
6.38 s (1H, 4′-H), 6.45–8.05 m (7H, Harom), 8.52 s (1H,
CH=N), 9.83 s (1H, CO2H). Mass spectrum: m/z 366
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 10 2013

DIKUSAR et al.
1520
1
[M]+. Found, %: C 65.92; H 5.14; N 7.19. C20H18N2O5.
Calculated, %: C 65.57; H 4.95; N 7.65. M 366.37.
809, 770, 755, 720, 689 (δCHarom). H NMR spectrum,
δ, ppm: 1.36 t (3H, MeCH2), 2.25 s (3H, Me), 4.04 q
(2H, MeCH2), 5.29 s (2H, CH2), 6.49 s (1H, 4′-H),
7.19–7.70 m (12H, Harom), 8.52 s (1H, CH=N). Mass
spectrum: m/z 412 [M]+. Found, %: C 75.90; H 5.99;
N 6.23. C26H24N2O3. Calculated, %: C 75.71; H 5.86;
N 6.79. M 412.48.
N-{(E)-3-Methoxy-4-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylidene}biphenyl-4-amine (XXI).
Yield 87%, mp 154–155°C. IR spectrum, ν, cm–1: 3134
(CHisox); 3079, 3067, 3034, 3003 (CHarom); 2963, 2923,
2853 (CHaliph); 1621 (C=N); 1602, 1587, 1510, 1483
(C=Carom); 1422 (C=Nisox); 1267, 1231, 1158, 1140,
1032, 1004 (C–O); 888, 870, 842, 810, 786, 766, 720,
N-{(E)-3-Ethoxy-4-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylidene}-4-phenoxyaniline (XXV).
Yield 81%, mp 121–122°C. IR spectrum, ν, cm–1: 3145
(CHisox); 3080, 3070, 3040, 3006 (CHarom); 2982, 2929,
2873, 2855 (CHaliph); 1624 (C=N); 1589, 1516, 1499,
1486 (C=Carom); 1422 (C=Nisox); 1268, 1232, 1207,
1125, 1098, 1040, 1020, 1009 (C–O); 886, 862, 833,
1
690 (δCHarom). H NMR spectrum, δ, ppm: 2.25 s (3H,
Me), 3.86 s (3H, MeO), 5.30 s (2H, CH2), 6.49 s (1H,
4′-H), 7.12–7.68 m (12H, Harom), 8.57 s (1H, CH=N).
Mass spectrum: m/z 398 [M]+. Found, %: C 75.67;
H 5.66; N 6.64. C25H22N2O3. Calculated, %: C 75.36;
H 5.57; N 7.03. M 398.45.
1
821, 798, 773, 695 (δCHarom). H NMR spectrum, δ,
ppm: 1.49 t (3H, MeCH2), 2.30 s (3H, Me), 4.20 q
(2H, MeCH2), 5.25 s (2H, CH2), 6.17 s (1H, 4′-H),
6.85–7.66 m (12H, Harom), 8.37 s (1H, CH=N). Mass
spectrum: m/z 428 [M]+. Found, %: C 73.12; H 5.84;
N 6.20. C26H24N2O4. Calculated, %: C 72.88; H 5.65;
N 6.54. M 428.48.
4-{(E)-3-Ethoxy-4-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylideneamino}benzoic acid (XXVI).
Yield 75%, mp 205–206°C. IR spectrum, ν, cm–1: 3139
(CHisox); 3074, 3048, 3010 (CHarom); 2977, 2924, 2864,
2854 (CHaliph); 1677 (C=O); 1630 (C=N); 1594, 1581,
1514 (C=Carom); 1429 (C=Nisox); 1273, 1233, 1164,
1135, 1125, 1042, 1010 (C–O); 890, 860, 830, 804,
780, 765, 740, 702, 663, 620 (δCHarom). 1H NMR spec-
trum, δ, ppm: 1.36 t (3H, MeCH2), 2.25 s (3H, Me),
4.19 q (2H, MeCH2), 5.33 s (2H, CH2), 6.49 s (1H,
4′-H), 7.04–7.98 m (7H, Harom), 8.53 s (1H, CH=N),
9.84 s (1H, CO2H). Mass spectrum: m/z 380 [M]+.
Found, %: C 66.47; H 5.52; N 7.05. C21H20N2O5. Cal-
culated, %: C 66.31; H 5.30; N 7.36. M 380.39.
N-{(E)-3-Methoxy-4-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylidene}-4-phenoxyaniline (XXII).
Yield 80%, mp 103–104°C. IR spectrum, ν, cm–1: 3135
(CHisox); 3086, 3070, 3065, 3035, 3005 (CHarom); 2968,
2924, 2870, 2855 (CHaliph); 1621 (C=N); 1599, 1588,
1587, 1511, 1498, 1489 (C=Carom); 1421 (C=Nisox);
1258, 1227, 1206, 1158, 1138, 1101, 1031, 1017, 1005
(C–O); 890, 873, 838, 819, 790, 763, 693 (δCHarom).
1H NMR spectrum, δ, ppm: 2.31 s (3H, Me), 3.99 s
(3H, MeO), 5.26 s (2H, CH2), 6.19 s (1H, 4′-H), 6.90–
7.72 m (12H, Harom), 8.39 s (1H, CH=N). Mass spec-
trum: m/z 414 [M]+. Found, %: C 72.75; H 5.17;
N 6.29. C25H22N2O4. Calculated, %: C 72.45; H 5.35;
N 6.76. M 414.45.
4-{(E)-3-Methoxy-4-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylideneamino}benzoic acid (XXIII).
Yield 78%, mp 232–233°C. IR spectrum, ν, cm–1: 3139
(CHisox); 3064, 3048, 3019 (CHarom); 2970, 2923, 2860,
2840 (CHaliph); 1671 (C=O); 1631 (C=N); 1593, 1583,
1520 (C=Carom); 1420 (C=Nisox); 1275, 1230, 1159,
1142, 1125, 1105, 1022, 1004 (C–O); 890, 876, 860,
830, 815, 773, 765, 740, 702, 663, 620 (δCHarom).
1H NMR spectrum, δ, ppm: 2.24 s (3H, Me), 3.89 s
(3H, MeO), 5.35 s (2H, CH2), 6.37 s (1H, 4′-H), 6.40–
8.00 m (7H, Harom), 8.51 s (1H, CH=N), 9.86 s (1H,
CO2H). Mass spectrum: m/z 366 [M]+. Found, %:
C 65.33; H 5.10; N 7.24. C20H18N2O5. Calculated, %:
C 65.57; H 4.95; N 7.65. M 366.37.
Schiff bases XXVII–XXXIV (general procedure).
A solution of 10 mmol of aldehyde VI–IX and 5 mmol
of aromatic diamine XIII or XIV in 50 ml of anhy-
drous methanol was heated for 45 min under reflux.
Schiff bases XXVII–XXXIV were isolated as de-
scribed above for XV–XXVI.
N,N′-Bis{(E)-4-[(3-methyl-1,2-oxazol-5-yl)me-
thoxy]benzylidene}benzene-1,4-diamine (XXVII).
Yield 81%, mp 238–239°C. IR spectrum, ν, cm–1: 3131
(CHisox); 3070, 3033, 3005 (CHarom); 2964, 2924, 2854
(CHaliph); 1618 (C=N); 1598, 1574, 1510 (C=Carom);
1420 (C=Nisox); 1243, 1167, 1004 (C–O); 886, 842,
N-{(E)-3-Ethoxy-4-[(3-methyl-1,2-oxazol-5-yl)-
methoxy]benzylidene}biphenyl-4-amine (XXIV).
Yield 88%, mp 137–138°C. IR spectrum, ν, cm–1: 3135
(CHisox); 3082, 3056, 3033, 3001 (CHarom); 2989, 2966,
2925, 2871, 2860 (CHaliph); 1625 (C=N); 1590, 1581,
1509, 1485 (C=Carom); 1432 (C=Nisox); 1266, 1234,
1165, 1141, 1019, 1040 (C–O); 899, 865, 836, 820,
1
825, 795 (δCHarom). H NMR spectrum, δ, ppm: 2.24 s
(6H, Me), 5.30 s (4H, CH2), 6.49 s (2H, 4′-H), 6.85–
7.95 m (12H, Harom), 8.54 s (2H, CH=N). Mass spec-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 10 2013

SYNTHESIS OF FUNCTIONALLY SUBSTITUTED ISOXAZOLE-CONTAINING
1521
trum: m/z 506 [M]+. Found, %: C 71.58; H 5.43;
N 10.52. C30H26N4O4. Calculated, %: C 71.13; H 5.17;
N 11.06. M 506.55.
4′-H), 6.90–7.73 m (10H, Harom), 8.53 s (2H, CH=N).
Mass spectrum: m/z 566 [M]+. Found, %: C 68.15;
H 5.42; N 9.37. C32H30N4O6. Calculated, %: C 67.83;
H 5.34; N 9.89. M 566.60.
N,N′-Bis{(E)-4-[(3-methyl-1,2-oxazol-5-yl)me-
thoxy]benzylidene}biphenyl-4,4′-diamine (XXVIII).
Yield 79%, mp 187–188°C. IR spectrum, ν, cm–1: 3135
(CHisox); 3069, 3030, 3005 (CHarom); 2964, 2923, 2853
(CHaliph); 1621 (C=N); 1605, 1573, 1508, 1490
(C=Carom); 1422 (C=Nisox); 1239, 1167, 1111, 1018,
N,N′-Bis{(E)-3-methoxy-4-[(3-methyl-1,2-oxazol-
5-yl)methoxy]benzylidene}biphenyl-4,4′-diamine
(XXXII). Yield 81%, mp 192–193°C. IR spectrum, ν,
cm–1: 3135 (CHisox); 3070, 3050, 3030 (CHarom); 2974,
2927, 2900, 2852 (CHaliph); 1618 (C=N); 1610, 1581,
1510, 1493 (C=Carom); 1417 (C=Nisox); 1274, 1232,
1143, 1032, 1005 (C–O); 896, 871, 828, 809 (δHarom).
1H NMR spectrum, δ, ppm: 2.25 s (6H, Me), 3.86 s
(6H, MeO), 5.31 s (4H, CH2), 6.47 s (2H, 4′-H), 6.54–
7.74 m (14H, Harom), 8.56 s (2H, CH=N). Mass spec-
trum: m/z 642 [M]+. Found, %: C 71.45; H 5.45;
N 8.38. C38H34N4O6. Calculated, %: C 71.01; H 5.33;
N 8.72. M 642.70.
1
1008 (C–O); 888, 835, 809 (δCHarom). H NMR spec-
trum, δ, ppm: 2.25 s (6H, Me), 5.34 s (4H, CH2), 6.43 s
(2H, 4′-H), 6.52–7.95 m (16H, Harom), 8.60 s (2H,
CH=N). Mass spectrum: m/z 582 [M]+. Found, %:
C 74.37; H 5.32; N 9.17. C36H30N4O4. Calculated, %:
C 74.21; H 5.19; N 9.62. M 582.65.
N,N′-Bis{(E)-4-methoxy-3-[(3-methyl-1,2-oxazol-
5-yl)methoxy]benzylidene}benzene-1,4-diamine
(XXIX). Yield 89%, mp 189–190°C. IR spectrum, ν,
cm–1: 3138 (CHisox); 3070, 3055, 3030, 3001 (CHarom);
2969, 2929, 2852, 2840 (CHaliph); 1617 (C=N); 1596,
1577, 1517 (C=Carom); 1425 (C=Nisox); 1268, 1239,
1212, 1168, 1135, 1020 (C–O); 867, 840, 815, 799
N,N′-Bis{(E)-3-ethoxy-4-[(3-methyl-1,2-oxazol-
5-yl)methoxy]benzylidene}benzene-1,4-diamine
(XXXIII). Yield 87%, mp 192–193°C. IR spectrum, ν,
cm–1: 3133 (CHisox); 3077, 3043, 3028 (CHarom); 2975,
2928, 2873 (CHaliph); 1617 (C=N); 1595, 1577, 1515
(C=Carom); 1424 (C=Nisox); 1268, 1232, 1210, 1180,
1131, 1046, 1000 (C–O); 894, 866, 838, 820, 810
1
(δCHarom). H NMR spectrum, δ, ppm: 2.23 s (6H,
Me), 3.87 s (6H, MeO), 5.31 s (4H, CH2), 6.48 s (2H,
4′-H), 6.90–7.75 m (10H, Harom), 8.53 s (2H, CH=N).
Mass spectrum: m/z 566 [M]+. Found, %: C 68.10;
H 5.45; N 9.44. C32H30N4O6. Calculated, %: C 67.83;
H 5.34; N 9.89. M 566.60.
1
(δCHarom). H NMR spectrum, δ, ppm: 1.32 t (6H,
MeCH2), 2.22 s (6H, Me), 4.08 q (4H, MeCH2), 5.32 s
(4H, CH2), 6.46 s (2H, 4′-H), 7.12–7.65 m (10H,
Harom), 8.49 s (2H, CH=N). Mass spectrum: m/z 594
[M]+. Found, %: C 68.93; H 5.91; N 9.16. C34H34N4O6.
Calculated, %: C 68.67; H 5.76; N 9.42. M 594.66.
N,N′-Bis{(E)-4-methoxy-3-[(3-methyl-1,2-oxazol-
5-yl)methoxy]benzylidene}biphenyl-4,4′-diamine
(XXX). Yield 86%, mp 202–203°C. IR spectrum, ν,
cm–1: 3133 (CHisox); 3068, 3030, 3002 (CHarom); 2964,
2926, 2865, 2852 (CHaliph); 1621 (C=N); 1595, 1576,
1512, 1489 (C=Carom); 1434 (C=Nisox); 1269, 1240,
1213, 1160, 1138, 1017 (C–O); 890, 862, 820
N,N′-Bis{(E)-3-ethoxy-4-[(3-methyl-1,2-oxazol-
5-yl)methoxy]benzylidene}biphenyl-4,4′-diamine
(XXXIV). Yield 85%, mp 213–214°C. IR spectrum, ν,
cm–1: 3133 (CHisox); 3070, 3054, 3032 (CHarom); 2975,
2926, 2854 (CHaliph); 1623 (C=N); 1594, 1579, 1514,
1491 (C=Carom); 1420 (C=Nisox); 1268, 1235, 1173,
1027, 1043, 1007 (C–O); 895, 872, 840, 820, 807
1
(δCHarom). H NMR spectrum, δ, ppm: 2.25 s (6H,
Me), 3.85 s (6H, MeO), 5.29 s (4H, CH2), 6.47 s (2H,
4′-H), 6.50–7.75 m (14H, Harom), 8.54 s (2H, CH=N).
Mass spectrum: m/z 642 [M]+. Found, %: C 71.39;
H 5.15; N 9.00. C38H34N4O6. Calculated, %: C 71.01;
H 5.33; N 8.72. M 642.70.
1
(δCHarom). H NMR spectrum, δ, ppm: 1.33 t (6H,
MeCH2), 2.25 s (6H, Me), 4.09 q (4H, MeCH2), 5.32 s
(4H, CH2), 6.43 s (2H, 4′-H), 6.54–7.74 m (14H,
H
arom), 8.54 s (2H, CH=N). Mass spectrum: m/z 670
[M]+. Found, %: C 71.88; H 5.96; N 7.97. C40H38N4O6.
Calculated, %: C 71.63; H 5.71; N 8.35. M 670.75.
N,N′-Bis{(E)-3-methoxy-4-[(3-methyl-1,2-oxazol-
5-yl)methoxy]benzylidene}benzene-1,4-diamine
(XXXI). Yield 85%, mp 197–198°C. IR spectrum, ν,
cm–1: 3130 (CHisox); 3080, 3053, 3011 (CHarom); 2960,
2940, 2855 (CHaliph); 1619 (C=N); 1597, 1581, 1515,
1509 (C=Carom); 1419 (C=Nisox); 1273, 1230, 1217,
1140, 1127, 1031, 1007 (C–O); 890, 863, 820, 805
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 10 2013

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