Synthesis of 5-arylisoxazole-3-carboxylates derived from salicylaldehyde

Article abstract of DOI:10.1134/S1070428015010066

A procedure has been developed for the synthesis of 5-arylisoxazole-3-carboxylates on the basis of phenols and oximes derived from salicylaldehyde. Selective reduction of 4-(2-ethoxybenzylideneaminophenyl) 5-arylisoxazole-3-carboxylates afforded the corresponding amines.

Full text of DOI:10.1134/S1070428015010066

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 1, pp. 33–41. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © S.K. Petkevich, E.A. Dikusar, V.I. Potkin, I.V. Mikhei, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 1,
pp. 40–47.
Synthesis of 5-Arylisoxazole-3-carboxylates
Derived from Salicylaldehyde
S. K. Petkevich, E. A. Dikusar, V. I. Potkin, and I. V. Mikhei
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: dikusar@ifoch.bas-net.by
Received: June 14, 2014
Abstract—A procedure has been developed for the synthesis of 5-arylisoxazole-3-carboxylates on the basis of
phenols and oximes derived from salicylaldehyde. Selective reduction of 4-(2-ethoxybenzylideneaminophenyl)
5
-arylisoxazole-3-carboxylates afforded the corresponding amines.
DOI: 10.1134/S1070428015010066
Like other isoxazole derivatives [1, 2], 5-arylisoxa-
zole-3-carboxylic acid esters exhibit various kinds
of biological activity, while natural alcohol and phenol
fragments are capable of acting as vehicles for tar-
geted delivery of pharmacophoric heterocyclic com-
pounds [3–6].
11–19, 23–31, and 33–38 from alcohols and phenols
derived from salicylaldehyde (1). Salicylaldehyde (1)
is a natural o-aldehydophenol occurring in essential
oils of some spirea (Spiraea ulmaria, Spiraea digitata)
and tobacco species (Nicotiána solanaceae); it is also
used in perfumery and as fungicide [7, 8]. We believed
it reasonable to synthesize compounds 5–7, 11–19,
23–31, and 33–38 and test them for antitumor activity.
In the present article we describe a procedure for
the synthesis of 5-arylisoxazole-3-carboxylates 5–7,
Scheme 1.
CHO
CHO
CHO
OR1 R Br, EtOH, K CO
1
OH R COCl, Et O, Et N
2
O
R2
2
3
2
3
O
2
–4
1
5–7
CH OH
OR1
O
2
OR1 R COCl, Et O, Et N
2
NaBH4, i-PrOH
2 3
R2
O
8
–10
11–19
2
–4
OR1
OR1
NH OH· HCl
NaHCO3, EtOH
2
R2
2
R COCl, Et O, Et N
O
2
3
NOH
N
O
2
0–22
23–31
1
1
1
2
, 8, 11, 14, 17, 20, 23, 26, 29, R = Et; 3, 9, 12, 15, 18, 21, 24, 27, 30, R = Bu; 4, 10, 13, 16, 19, 22, 25, 28, 31, R = PhCH
2
;
2
R =
6 4 2 6 3
; 5, 11–13, 23–25, Ar = Ph; 6, 14–16, 26–28, Ar = 4-MeC H ; 7, 17–19, 29–31, Ar = 2,5-Me C H .
N
Ar
O
3
3

3
4
PETKEVICH et al.
Scheme 2.
OH
O
R2
OEt
OEt
2
4
-H NC H OH
R COCl, CH Cl Et N
2
6
4
2
2,
3
O
2
N
N
3
2
33–35
O
R2
OEt
NaBH(OAc)2, PhH
O
N
H
3
6–38
2
R =
; 33, 36, Ar = Ph; 34, 37, 4-MeC H ; 35, 38, Ar = 2,5-Me C H .
6
4
2
6
3
N
Ar
O
Esterification of salicylaldehyde (1) with 5-aryl-
isoxazole-3-carboxylates 4–6, 10–18, 22–33, and 36–38
are capable of inhibiting synaptic transmission, which
attracts strong interest from the viewpoint of develop-
ment of antitumor agents for chemotherapy of brain
tumors with concomitant ischemic processes.
isoxazole-3-carbonyl chlorides in anhydrous diethyl
ether in the presence of triethylamine gave esters 5–7
in 75–80% yield. Aldehyde 1 reacted with alkyl bro-
mides or benzyl chloride in ethanol in the presence of
potassium carbonate to form esters 2–4 which were
reduced with NaBH in isopropyl alcohol to alcohols
EXPERIMENTAL
4
8
3
8
–10, and the latter were treated with 5-arylisoxazole-
-carbonyl chlorides to obtain esters 11–19 (yield 74–
2%; Scheme 1). 2-Alkoxybenzaldehydes 2–4 reacted
The IR spectra were recorded from thin films or
KBr pellets on a Nicolet Protégé-460 spectrometer
with Fourier transform. The H and C NMR spectra
were recorded on a Bruker Avance-500 spectrometer
1
13
with hydroxylamine hydrochloride in ethanol in the
presence of NaHCO to produce the corresponding
oximes 20–22 which were converted into oxime esters
2
zole-3-carbonyl chlorides in anhydrous diethyl ether in
the presence of triethylamine at 0°C [6].
3
from solutions in CDCl (5–7, 11–17, 19, 23–31,
3
3
3–38) and DMSO-d (18); the chemical shifts were
3–31 (yield 72–78%) by the action of 5-arylisoxa-
6
measured relative to the residual proton and carbon
signals of the deuterated solvents. The mass spectra
(
electron impact, 70 eV) were obtained on a Hewlett
By condensation of 2-ethoxyphenyl ester 2 with
-aminophenol in anhydrous methanol we obtained
Packard 5890/5972 GC/MS system (HP-5MS capillary
column, 30 m×0.25 mm, film thickness 0.25 μm;
injector temperature 250°C).
4
known hydroxy-containing (E)-Schiff base 32 [6], and
the subsequent mild esterification of 32 with 5-aryl-
isoxazole-3-carbonyl chlorides in methylene chloride
in the presence of triethylamine afforded 65–75% of
esters 33–35. Careful reduction of 33–35 with
Salicylaldehyde (1) was distilled prior to use
(bp 197–198°C); its physicochemical constants, as
well as those of ethers 2–4, alcohols 8–10, oximes
20–22, and Schiff base 32, were consistent with
published data [6].
NaBH(OAc) in anhydrous benzene gave 76–85% of
benzylamino derivatives 36–38 in which the ester
3
moiety remained intact (Scheme 2).
Esters 5–7 and 11–19 (general procedure).
Salicylaldehyde (1), 10 mmol, was dissolved in 50 mL
of anhydrous diethyl ether, 11 mmol of the corre-
sponding 5-arylisoxazole-3-carbonyl chloride and
The structure of compounds 5–7, 11–19, 23–31,
and 33–38 was determined on the basis of their ele-
1
13
mental compositions, IR and H and C NMR spectra,
and GC/MS data. The electron-impact mass spectra of
1
1 mmol of anhydrous triethylamine were added, and
5
–7, 11–19, and 33–35 contained the molecular ion
the mixture was stirred for 5 h at 23°C. The precipitate
of triethylamine hydrochloride was filtered off, the fil-
trate was evaporated to a volume of 10 mL, 20 mL of
hexane was added to the residue, and the mixture was
peaks and appropriate fragment ion peaks.
Some of the synthesized compounds are now being
tested for neurotropic activity. It is believed that 5-aryl-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

SYNTHESIS OF 5-ARYLISOXAZOLE-3-CARBOXYLATES
35
1
3
cooled to –10°C. The precipitate was filtered off,
washed with hexane, and dried under reduced pressure.
C NMR spectrum, δ , ppm: 20.99 (Me), 21.10 (Me),
C
4
103.35 (C ), 123.41 (CHarom), 127.27 (CHarom), 129.11
(
(
CHarom), 131.63 (CHarom), 131.68 (CHarom), 131.72
CHarom), 135.61 (CHarom), 125.79, 127.99, 133.46,
2
-Formylphenyl 5-phenyl-1,2-oxazole-3-carbox-
ylate (5). Yield 77%, mp 158–160°C. IR spectrum,
–
1
136.20, 150.70, 155.74, 158.47, 172.69 (3-C=O),
1
Found, %: C 71.11; H 4.75; N 4.01. C H NO .
Calculated, %: C 71.02; H 4.71; N 4.36. M 321.33.
ν, cm : 3145, 3128, 3092, 3063, 3039, 3008, 2924,
875 (C–H), 2774 (O=C–H), 1754 (C=O, ester), 1697
CH=O), 1606, 1591, 1584, 1571, 1497, 1483,
459, 1437, 1403 (C=C, C=N), 1236, 1129 (C–O–C).
+
88.54 (CH=O). Mass spectrum: m/z 321 [M] .
2
(
1
9
15
4
1
1
H NMR spectrum, δ, ppm: 7.08 s (1H, 4-H), 7.37 m
2-Ethoxybenzyl 5-phenyl-1,2-oxazole-3-carbox-
(
7
1H, Harom), 7.49 m (4H, Harom), 7.69 m (1H, Harom),
ylate (11). Yield 82%, mp 84–85°C. IR spectrum,
–
1
.83 m (2H, Harom), 7.93 m (1H, Harom), 10.18 s (1H,
ν, cm : 3146, 3129, 3059, 3026, 2981, 2931, 2883
(C–H), 1731 (C=O), 1607, 1592, 1573, 1501, 1473,
1448 (C=C, C=N), 1246, 1148, 1124 (C–O–C).
1
3
4
CHO). C NMR spectrum, δ , ppm: 100.47 (C ),
C
1
1
1
1
23.39 (CHarom), 126.12 (2C, CHarom), 127.29 (CHarom),
29.33 (2C, CHarom), 131.16 (CHarom), 131.82 (CHarom),
35.60 (CHarom), 126.50, 127.94, 150.58, 156.10,
1
3
H NMR spectrum, δ, ppm: 1.41 t (3H, Me, J = 7 Hz),
3
4.05 q (2H, OCH
6.88 d (1H, Harom, J = 8.1 Hz), 6.92 s (1H, 4-H), 6.96 t
(1H, Harom, J = 8.1 Hz), 7.30 t (1H, Harom, J = 8.1 Hz),
, J = 7 Hz), 5.52 s (CH
C
H
),
2
3
2
6
4
58.31, 172.46 (3-C=O), 188.58 (CHO). Mass spec-
+
3
3
trum: m/z 293 [M] . Found, %: C 69.54; H 3.82;
N 4.48. C H NO . Calculated, %: C 69.62; H 3.78;
1
3
7.45 m (4H, Harom), 7.78 m (2H, Harom). C NMR spec-
trum, δ , ppm: 14.83 (Me), 63.32 (CH ), 63.70 (CH ),
9.99 (C ), 111.40 (CHarom), 120.31 (CHarom), 125.86
2C, CHarom), 129.11 (2C, CHarom), 129.81 (CHarom),
129.91 (CHarom), 130.76 (CHarom), 123.45, 126.59,
56.94, 157.00, 159.86, 171.61 (C=O). Mass spec-
1
7
11
4
N 4.78. M 293.27.
-Formylphenyl 5-(4-methylphenyl)-1,2-oxazole-
-carboxylate (6). Yield 80%, mp 153–154°C.
C
2
2
4
9
(
2
3
–
1
IR spectrum, ν, cm : 3137, 3102, 3073, 3059, 3033,
013, 2922, 2876 (C–H), 2772 (O=C–H), 1753
C=O, ester), 1694 (CH=O), 1605, 1593, 1583, 1567,
1
3
(
1
1
+
trum: m/z 323 [M] . Found, %: C 70.77; H 5.42;
N 3.97. C H NO . Calculated, %: C 70.58; H 5.30;
1
9
17
4
512, 1483, 1457, 1441, 1403 (C=C, C=N), 1237,
1
N 4.33. M 323.34.
114 (C–O–C). H NMR spectrum, δ, ppm: 2.42 s
(
3H, Me), 7.03 s (1H, 4-H), 7.31 d (2H, Harom,
2-Butoxybenzyl 5-phenyl-1,2-oxazole-3-carbox-
3
3
J = 8 Hz), 7.38 d (1H, H , J = 8 Hz), 7.48 t (1H,
ylate (12). Yield 80%, mp 113–115°C. IR spectrum,
arom
3
3
–1
Harom, J = 7.6 Hz), 7.69 t (1H, H , J = 7.6 Hz),
ν, cm : 3148, 3135, 3063, 3013, 2953, 2927, 2872
arom
3
7
.73 d (2H, Harom, J = 8 Hz), 7.95 d (1H, Harom,
J = 7.6 Hz), 10.19 s (1H, CHO). C NMR spec-
(C–H), 1726 (C=O), 1614, 1601, 1589, 1571, 1498,
1469, 1451, 1440, 1400 (C=C, C=N), 1246, 1148, 1112
3
13
4
1
trum, δ , ppm: 21.70 (Me), 99.88 (C ), 123.42
(
1
1
1
m/z 307 [M] . Found, %: C 70.02; H 4.25; N 4.17.
C H NO . Calculated, %: C 70.35; H 4.26; N 4.56.
M 307.30.
-Formylphenyl 5-(2,5-dimethylphenyl)-1,2-oxa-
zole-3-carboxylate (7). Yield 75%, mp 104–105°C.
(C–O–C). H NMR spectrum, δ, ppm: 0.96 t (3H, Me,
C
3
3
CHarom), 126.09 (2C, CHarom), 127.28 (CHarom),
30.03 (2C, CHarom), 131.70 (CHarom), 135.61 (CHarom),
23.84, 127.99, 141.66, 150.71, 156.04, 158.42,
J = 7.4 Hz), 1.50 sext (2H, CH Me, J = 7.4 Hz),
2
3
1.78 q (2H, OCH
CH
, J = 7 Hz), 4.01 t (2H, OCH
), 6.90 d (1H, Harom
J = 8.2 Hz), 6.92 s (1H, 4-H), 6.96 t (1H, Harom
,
,
,
2
2
2
3
J = 6.4 Hz), 5.52 s (CH
C H
6 4
2
3
3
72.71 (3-C=O), 188.55 (CHO). Mass spectrum:
+
3
J = 8.2 Hz), 7.32 t (1H, Harom, J = 8.2 Hz), 7.44 d
3
(1H, Harom, J = 8.2 Hz), 7.47 m (3H, Harom), 7.79 m
(2H, Harom). C NMR spectrum, δ
1
8
13
4
1
3
, ppm: 13.92 (Me),
C
1
6
9.38 (CH Me), 31.34 (OCH CH ), 63.46 (OCH ),
2
2
2
2
2
4
7.86 (OCH ), 100.04 (C ), 111.40 (CHarom), 120.32
2
–
1
(CHarom), 125.95 (2C, CHarom), 129.20 (2C, CHarom),
IR spectrum, ν, cm : 3174, 3141, 3103, 3083, 3036,
958, 2924, 2853 (C–H), 2766 (O=C–H), 1756 (C=O,
ester), 1698 (CH=O), 1605, 1582, 1505, 1481, 1455,
422, 1400 (C=C, C=N), 1232, 1150 (C–O–C).
1
1
30.00 (CHarom), 130.01 (CHarom), 130.88 (CHarom),
2
23.38, 126.71, 157.00, 157.27, 159.96, 171.69 (C=O).
+
Mass spectrum: m/z 351 [M] . Found, %: C 72.19;
1
1
H 6.01; N 3.68. C H NO . Calculated, %: C 71.78;
2
1
21
4
H NMR spectrum, δ, ppm: 2.39 s (3H, Me), 2.50 s
H 6.02; N 3.99. M 351.40.
(
(
7
7
3H, Me), 6.99 s (1H, 4-H), 7.21 s (2H, Harom), 7.39 d
3
3
1H, Harom, J = 8 Hz), 7.48 t (1H, H , J = 7.7 Hz),
2-(Benzyloxy)benzyl 5-phenyl-1,2-oxazole-3-car-
arom
3
.60 s (1H, Harom), 7.71 t (1H, H , J = 7.7 Hz),
.95 d (1H, Harom, J = 7.7 Hz), 10.20 s (1H, CHO).
boxylate (13). Yield 81%, mp 88–90°C. IR spectrum,
arom
3
–1
ν, cm : 3151, 3135, 3059, 3029, 2985, 2931, 2883
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

3
6
PETKEVICH et al.
(
C–H), 1716 (C=O), 1604, 1590, 1583, 1491, 1462,
443 (C=C, C=N), 1259, 1143, 1120 (C–O–C).
spectrum, δ , ppm: 13.88 (CH Me), 19.35 (CH Me),
C 2 2
1
21.52 (Me), 31.31 (OCH CH ), 63.35 (CH ), 63.81
2 2 2
1
4
H NMR spectrum, δ, ppm: 5.15 s (2H, PhCH O),
(CH ), 99.40 (C ), 111.35 (CHarom), 120.28 (CHarom),
2
2
5
.58 s (C H CH O), 6.91 s (1H, 4-H), 6.99 d (1H,
125.84 (2C, CHarom), 129.83 (2C, CHarom), 129.91
(CHarom), 129.95 (CHarom), 123.38, 123.99, 141.20,
156.90, 157.21, 159.99, 171.85 (C=O). Mass spec-
6
4
2
3
3
Harom, J = 8.2 Hz), 7.01 t (1H, H , J = 7.5 Hz),
7
7
arom
3
.34 m (2H, Harom), 7.38 t (2H, Harom, J = 7.4 Hz),
1
3
+
.48 m (6H, Harom), 7.80 m (2H, Harom). C NMR spec-
trum: m/z 365 [M] . Found, %: C 72.71; H 6.35;
4
trum, δ , ppm: 63.54 (CH ), 70.09 (CH ), 100.11 (C ),
N 3.49. C H NO . Calculated, %: C 72.31; H 6.34;
C
2
2
22 23
4
1
1
12.03 (CHarom), 120.90 (CHarom), 125.98 (2C, CHarom),
27.30 (2C, CHarom), 128.01 (CHarom), 128.66 (2C,
CHarom), 129.22 (2C, CHarom), 130.11 (CHarom), 130.23
CHarom), 130.87 (CHarom), 123.71, 126.71, 136.90,
56.87, 156.97, 160.00, 171.71 (C=O). Mass spec-
N 3.83. M 365.42.
2
-(Benzyloxy)benzyl 5-(4-methylphenyl)-1,2-oxa-
zole-3-carboxylate (16). Yield 76%, mp 116–117°C.
IR spectrum, ν, cm : 3141, 3088, 3065, 3030, 2935,
(
1
–1
2
1
1
2
923, 2854 (C–H), 1726 (C=O), 1613, 1606, 1594,
511, 1494, 1473, 1448, 1413 (C=C, C=N), 1252,
147, 1112 (C–O–C). H NMR spectrum, δ, ppm:
+
trum: m/z 385 [M] . Found, %: C 74.68; H 4.95;
N 3.41. C H NO . Calculated, %: C 74.79; H 4.97;
1
2
4
19
4
N 3.63. M 385.41.
-Ethoxybenzyl 5-(4-methylphenyl)-1,2-oxazole-
-carboxylate (14). Yield 75%, mp 98–99°C. IR spec-
.42 s (3H, Me), 5.15 s (2H, PhCH O), 5.57 s
2
2
(2H, C H CH O), 6.84 s (1H, 4-H), 6.98 d (1H, Harom,
6 4 2
3
3
3
J = 8.2 Hz), 7.01 t (1H, H
, J = 7.5 Hz),
arom
–
1
3
trum, ν, cm : 3137, 3065, 3042, 3008, 2983, 2925,
2
7.29 d (2H, Harom, J = 8.1 Hz), 7.33 m (2H, Harom),
3
856 (C–H), 1732 (C=O), 1618, 1607, 1595, 1501,
473, 1446 (C=C, C=N), 1251, 1148, 1124 (C–O–C).
7.37 t (2H, H , J = 7.4 Hz), 7.46 d (2H, Harom,
arom
3
3
1
J = 7.4 Hz), 7.48 d (1H, H , J = 7.4 Hz), 7.69 d
(2H, Harom, J = 8.1 Hz). C NMR spectrum, δ , ppm:
arom
1
3
13
H NMR spectrum, δ, ppm: 1.42 t (3H, CH Me,
J = 7 Hz), 2.40 s (3H, Me), 4.07 q (2H, CH Me,
J = 7 Hz), 5.51 s (C H CH ), 6.87 s (1H, 4-H),
2
C
3
3
4
2
21.30 (Me), 63.48 (CH ), 70.16 (CH ), 99.52 (C ),
2
2
6
4
2
112.10 (CHarom), 120.94 (CHarom), 125.95 (2C, CHarom),
127.31 (2C, CHarom), 128.01 (CHarom), 128.67 (2C,
CHarom), 129.91 (2C, CHarom), 130.08 (CHarom), 130.22
(CHarom), 123.84, 124.09, 136.95, 141.29, 156.90,
156.95, 160.09, 171.85 (C=O). Mass spectrum:
3
6
.89 d (1H, Harom, J = 8.1 Hz), 6.96 t (1H, Harom,
3
3
J = 8.1 Hz), 7.27 d (2H, H
, J = 8.1 Hz),
arom
3
7
.31 t (1H, Harom, J = 8.1 Hz), 7.44 d (1H, Harom,
3
3
13
J = 8.1 Hz), 7.68 d (2H, Harom, J = 8.1 Hz). C NMR
spectrum, δ , ppm: 14.92 (CH Me), 21.59 (Me), 63.36
+
m/z 399 [M] . Found, %: C 75.54; H 5.35; N 3.24.
C
2
4
(
CH ), 63.80 (CH ), 99.47 (C ), 111.48 (CHarom),
C H NO . Calculated, %: C 75.17; H 5.30; N 3.51.
2
2
25 21
4
1
20.39 (CHarom), 125.91 (2C, CHarom), 129.87 (3C,
M 399.44.
CHarom), 129.95 (CHarom), 123.49, 124.03, 141.26,
56.92, 157.09, 160.05, 171.92 (C=O). Mass spec-
trum: m/z 337 [M] . Found, %: C 71.20; H 5.69;
2
-Ethoxybenzyl 5-(2,5-dimethylphenyl)-1,2-oxa-
1
zole-3-carboxylate (17). Yield 80%, mp 118–120°C.
IR spectrum, ν, cm : 3182, 3132, 3092, 3049, 3026,
972, 2926, 2901, 2866 (C–H), 1736 (C=O), 1604,
591, 1572, 1500, 1477, 1458 (C=C, C=N), 1250,
+
–1
N 3.78. C H NO . Calculated, %: C 71.20; H 5.68;
2
0
19
4
2
1
N 4.15. M 337.37.
-Butoxybenzyl 5-(4-methylphenyl)-1,2-oxazole-
-carboxylate (15). Yield 74%, mp 112–113°C.
1
2
1156, 1119 (C–O–C). H NMR spectrum, δ, ppm:
3
3
1.43 t (3H, CH
2.46 s (3H, Me), 4.07 q (2H, CH
5.53 s (2H, CH O), 6.83 s (1H, 4-H), 6.89 d (1H,
arom, J = 8.1 Hz), 6.97 t (1H, Harom, J = 8.1 Hz),
7.18 s (2H, Harom), 7.31 t (1H, Harom, J = 8.1 Hz),
2
Me, J = 7 Hz), 2.37 s (3H, Me),
–
1
3
IR spectrum, ν, cm : 3138, 3065, 3037, 3013,
Me, J = 7 Hz),
2
2
1
1
0
966, 2935, 2865 (C–H), 1723 (C=O), 1618, 1606,
592, 1503, 1473, 1445, 1414 (C=C, C=N), 1253,
2
3
3
H
1
3
146, 1123 (C–O–C). H NMR spectrum, δ, ppm:
3
3
.97 t (3H, CH Me, J = 7.4 Hz), 1.50 sext (2H,
7.45 d (1H
, J = 8.1 Hz), 7.55 s (1H, Harom).
2
arom
3
13
CH Me, J = 7.4 Hz), 1.78 q (2H, OCH CH ,
C NMR spectrum, δ , ppm: 14.87 (CH Me),
20.86 (Me), 20.96 (Me), 63.32 (CH
102.90 (C ), 111.43 (CHarom), 120.34 (CHarom), 128.90
(CHarom), 129.87 (CHarom), 129.91 (CHarom), 131.37
(CHarom), 131.45 (CHarom), 123.41, 125.92, 133.23,
135.97, 156.61, 157.04, 160.10, 171.85 (C=O). Mass
2
2
2
C
2
3
3
J = 7 Hz), 2.40 s (3H, Me), 4.00 t (2H, OCH CH ,
J = 6.4 Hz), 5.51 s (C H CH ), 6.87 s (1H, 4-H),
2
), 63.74 (CH ),
2
2
2
4
6
4
2
3
6
.90 d (1H, Harom, J = 8.1 Hz), 6.96 t (1H, Harom,
3
3
J = 8.1 Hz), 7.27 d (2H, Harom, J = 8.1 Hz),
3
7
.32 t (1H, Harom, J = 8.1 Hz), 7.44 d (1H, Harom,
3
3
13
+
J = 8.1 Hz), 7.68 d (2H, Harom, J = 8.1 Hz). C NMR
spectrum: m/z 351 [M] . Found, %: C 71.99; H 6.03;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

SYNTHESIS OF 5-ARYLISOXAZOLE-3-CARBOXYLATES
N 3.64. C H NO . Calculated, %: C 71.78; H 6.02;
37
and 11 mmol of anhydrous triethylamine in 50 mL of
anhydrous diethyl ether was cooled to –10°C, 10 mmol
of oxime 20–22 was added under stirring, and the
mixture was stirred for 5 h at –10°C. The precipitate of
triethylamine hydrochloride was filtered off, the
filtrate was evaporated under reduced pressure to
a volume of 10 mL, 20 mL of hexane was added to the
residue, and the mixture was cooled to –10°C. The
precipitate was filtered off, washed with hexane, and
dried under reduced pressure.
2
1
21
4
N 3.99. M 351.40.
-Butoxybenzyl 5-(2,5-dimethylphenyl)-1,2-oxa-
zole-3-carboxylate (18). Yield 79%, mp 83–85°C.
2
–
1
IR spectrum, ν, cm : 3162, 3125, 3076, 3043, 3027,
2
1
1
968, 2957, 2938, 2926, 2869 (C–H), 1738 (C=O),
602, 1592, 1568, 1508, 1497, 1452 (C=C, C=N),
1
246, 1157, 1109 (C–O–C). H NMR spectrum,
3
δ, ppm: 0.85 t (3H, CH Me, J = 7.4 Hz), 1.39 sext
2
3
(
2H, CH Me, J = 7.4 Hz), 1.65 q (2H, OCH CH ,
J = 6.9 Hz), 2.31 s (3H, Me), 2.40 s (3H, Me), 3.99 t
2
2
2
3
(E)-2-Ethoxybenzaldehyde O-(5-phenyl-1,2-oxa-
3
zole-3-carbonyl) oxime (23). Yield 77%, mp 118–
(
2H, OCH Me, J = 6.3 Hz), 5.41 s (C H CH ),
2
6
4
2
–
1
3
120°C. IR spectrum, ν, cm : 3150, 3133, 3059, 3040,
2981, 2924, 2854 (C–H), 1763 (C=O), 1610, 1601,
1572, 1491, 1448, 1414 (C=C, C=N), 1260, 1225,
6
.96 t (1H, Harom, J = 8.1 Hz), 7.03 d (1H, Harom,
3
J = 8.1 Hz), 7.15 s (1H, 4-H), 7.23 d (1H, Harom,
J = 7.9 Hz), 7.26 d (1H, Harom, J = 7.9 Hz),
3
3
1
3
1116 (C–O–C). H NMR spectrum, δ, ppm: 1.46 t (3H,
7
.35 t (1H, Harom, J = 8.1 Hz), 7.43 d (1H, Harom,
3
3
3
13
Me, J = 6.9 Hz), 4.10 q (2H, CH
2
, J = 6.9 Hz),
J = 8.1 Hz), 7.57 s (1H, Harom). C NMR spectrum,
δ , ppm: 14.20 (CH Me), 19.35 (CH Me), 20.90 (Me),
3
6
.93 d (1H, Harom, J = 8.3 Hz), 7.00 t (1H, Harom,
C
2
2
3
J = 7.6 Hz), 7.07 s (1H, 4-H), 7.45 t (1H, Harom
J = 7.9 Hz), 7.51 m (3H, Harom), 7.84 m (2H, Harom),
.05 d (1H, Harom, J = 7.8 Hz), 9.08 s (1H, N=CH).
C NMR spectrum, δ , ppm: 14.96 (Me), 64.29 (CH ),
,
2
0.97 (Me), 31.33 (OCH CH ), 63.57 (CH ), 67.94
2 2 2
3
4
(CH ), 103.70 (C ), 112.41 (CHarom), 120.74 (CHarom),
2
3
8
1
1
1
29.32 (CHarom), 130.75 (CHarom), 130.84 (CHarom),
32.04 (2C, CHarom), 123.54, 125.95, 133.59, 136.31,
13
C
2
4
1
00.46 (C ), 112.16 (CHarom), 120.90 (CHarom), 126.16
56.92, 157.54, 159.91, 172.05 (C=O). Mass spec-
(
2C, CHarom), 127.85 (CHarom), 129.36 (2C, CHarom),
+
trum: m/z 379 [M] . Found, %: C 72.52; H 6.16;
N 3.68. C H NO . Calculated, %: C 72.80; H 6.64;
N 3.69. M 379.45.
-(Benzyloxy)benzyl 5-(2,5-dimethylphenyl)-1,2-
oxazole-3-carboxylate (19). Yield 78%, mp 63–64°C.
IR spectrum, ν, cm : 3153, 3062, 3049, 3033, 2954,
2
1
1
1
31.12 (CHarom), 133.80 (CHarom), 154.48 (N=CH),
18.11, 126.65, 155.96, 157.89, 158.39, 172.07 (C=O).
Found, %: C 67.47; H 4.68; N 7.94. C H N O .
2
3
25
4
1
9
16
2
4
2
Calculated, %: C 67.85; H 4.79; N 8.33.
E)-2-Butoxybenzaldehyde O-(5-phenyl-1,2-oxa-
zole-3-carbonyl) oxime (24). Yield 72%, mp 130–
1
2
1
(
–
1
923, 2853 (C–H), 1747 (C=O), 1604, 1591, 1579,
–1
31°C. IR spectrum, ν, cm : 3146, 3130, 3074, 3053,
557, 1496, 1452, 1425 (C=C, C=N), 1239, 1151, 1111
964, 2939, 2877 (C–H), 1752 (C=O), 1610, 1601,
1
(
C–O–C). H NMR spectrum, δ, ppm: 2.39 s (3H, Me),
570, 1493, 1477, 1460, 1435 (C=C, C=N), 1260,
1
2
.47 s (3H, Me), 5.15 s (2H, PhCH O), 5.58 s
2
1223, 1124 (C–O–C). H NMR spectrum, δ, ppm:
3
3
(
C H CH O), 6.81 s (1H, 4-H), 6.98 d (1H, H , J =
6 4 2 arom
0.99 t (3H, Me, J = 7.4 Hz), 1.50 sext (2H, CH Me,
2
3
3
3
8
.5 Hz), 7.01 t (1H, Harom, J = 7.5 Hz), 7.20 s (2H,
J = 7.4 Hz), 1.80 q (2H, OCH CH , J = 7 Hz),
2
2
3
3
Harom), 7.32 m (2H, Harom), 7.37 t (2H, H , J =
7
Harom, J = 7.5 Hz), 7.56 s (1H, Harom). C NMR
spectrum, δ, ppm: 21.01 (Me), 21.10 (Me), 63.54
arom
4.02 t (2H, OCH Me, J = 6.4 Hz), 6.92 d (1H, Harom,
2
3
3
3
.4 Hz), 7.47 d (2H, H , J = 7.4 Hz), 7.49 d (1H,
arom
J = 8.4 Hz), 6.98 t (1H, Harom, J = 7.5 Hz), 7.05 s
3
13
3
(1H, 4-H), 7.43 t (1H, Harom
, J = 7.4 Hz), 7.49 m
(3H, Harom), 7.83 m (2H, Harom), 8.04 d (1H, Harom,
4
3
13
(
CH ), 70.17 (CH ), 103.06 (C ), 112.10 (CHarom),
J = 7.3 Hz), 9.04 s (1H, N=CH). C NMR spec-
trum, δ , ppm: 13.96 (CH Me), 19.42 (CH Me),
2
2
1
1
1
1
1
20.96 (CHarom), 127.33 (2C, CHarom), 128.05 (CHarom),
28.71 (2C, CHarom), 129.09 (CHarom), 130.12 (CHarom),
30.31 (CHarom), 131.49 (CHarom), 131.56 (CHarom),
23.83, 126.09, 133.39, 136.12, 136.98, 156.69,
C
2
2
4
31.28 (OCH CH ), 68.35 (OCH ), 100.41 (C ),
2
2
2
112.11 (CHarom), 120.77 (CHarom), 126.09 (2C, CHarom),
127.79 (CHarom), 129.31 (2C, CHarom), 131.07 (CHarom),
133.76 (CHarom), 154.28 (N=CH), 118.04, 126.56,
155.90, 157.83, 158.47, 172.00 (C=O). Found, %:
56.94, 160.25, 172.00 (C=O). Mass spectrum:
+
m/z 413 [M] . Found, %: C 75.28; H 5.64; N 3.24.
C H NO . Calculated, %: C 75.53; H 5.61; N 3.39.
M 413.47.
C 69.01; H 5.44; N 7.29. C21
C 69.22; H 5.53; N 7.69.
H N O . Calculated, %:
20 2 4
2
6
23
4
Oxime esters 23–31 (general procedure). A solu-
tion of 11 mmol of 5-arylisoxazole-3-carbonyl chloride
(E)-2-(Benzyloxy)benzaldehyde O-(5-phenyl-
1,2-oxazole-3-carbonyl) oxime (25). Yield 76%,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

3
8
PETKEVICH et al.
–
1
mp 148–150°C. IR spectrum, ν, cm : 3149, 3109,
13.95 (CH Me), 19.41 (CH Me), 21.65 (Me), 31.33
(OCH CH ), 68.18 (OCH ), 99.81 (C ), 112.11
2 2 2
2
2
4
3
1
1
063, 3026, 3007, 2923, 2854 (C–H), 1751 (C=O),
611, 1600, 1570, 1489, 1450, 1436 (C=C, C=N),
239, 1215, 1114 (C–O–C). H NMR spectrum, δ,
ppm: 5.13 s (PhCH ), 7.02 m (2H, Harom), 7.04 s
1H, 4-H), 7.37 m (1H, Harom), 7.43 m (5H, Harom),
.49 m (3H, Harom), 7.82 m (2H, Harom), 8.08 d (1H,
Harom, J = 7.6 Hz), 9.07 s (1H, N=CH). C NMR
spectrum, δ , ppm: 70.63 (PhCH ), 100.35 (C ),
12.62 (CHarom), 121.28 (CHarom), 126.06 (2C, CHarom),
27.72 (2C, CHarom), 128.01 (CHarom), 128.42 (CHarom),
28.86 (2C, CHarom), 129.28 (2C, CHarom), 131.04
(CHarom), 120.66 (CHarom), 126.02 (2C, CHarom), 127.81
(CHarom), 129.96 (2C, CHarom), 133.73 (CHarom), 154.26
(N=CH), 118.06, 123.86, 141.52, 155.81, 157.95,
158.47, 172.20 (C=O). Found, %: C 69.69; H 5.92;
N 7.25. C H N O . Calculated, %: C 69.83; H 5.86;
1
2
(
7
22
22
2
4
3
13
N 7.40.
E)-2-(Benzyloxy)benzaldehyde O-[5-(4-methyl-
phenyl)-1,2-oxazole-3-carbonyl] oxime (28). Yield
4
C
2
(
1
1
1
(
1
–1
7
3
1
6%, mp 127–128°C. IR spectrum, ν, cm : 3143,
061, 3033, 2923, 2874, 2854 (C–H), 1755 (C=O),
611, 1599, 1571, 1511, 1489, 1447, 1413 (C=C,
C=N), 1247, 1222, 1105 (C–O–C). H NMR spectrum,
CHarom), 133.75 (CHarom), 154.20 (N=CH), 118.38,
26.53, 136.10, 155.80, 157.75, 158.01, 171.96 (C=O).
Found, %: C 72.13; H 4.64; N 6.70. C H N O . Cal-
1
2
4
18
2
4
δ, ppm: 2.41 s (3H, Me), 5.13 s (PhCH ), 6.98 s (1H,
2
culated, %: C 72.35; H 4.55; N 7.03.
E)-2-Ethoxybenzaldehyde O-[5-(4-methylphe-
nyl)-1,2-oxazole-3-carbonyl] oxime (26). Yield 78%,
3
4
-H), 7.02 m (2H, Harom), 7.29 d (2H, Harom, J = 8 Hz),
(
7.36 m (1H, Harom), 7.43 m (5H, Harom), 7.71 d (2H,
3
3
Harom, J = 8 Hz), 8.08 d (1H, H , J = 7.6 Hz),
arom
–
1
13
mp 145–147°C. IR spectrum, ν, cm : 3135, 3073,
9.07 s (1H, N=CH). C NMR spectrum, δ , ppm:
21.66 (Me), 70.65 (CH ), 99.77 (C ), 112.63 (CHarom),
C
4
3
1
1
043, 2980, 2923, 2857 (C–H), 1758 (C=O), 1610,
599, 1573, 1510, 1493, 1483, 1451 (C=C, C=N),
259, 1228, 1132 (C–O–C). H NMR spectrum,
δ, ppm: 1.45 t (3H, CH Me, J = 6.9 Hz), 2.41 s (3H,
Me), 4.09 q (2H, CH Me, J = 6.9 Hz), 6.92 d (1H,
2
121.30 (CHarom), 126.02 (2C, CHarom), 127.74 (2C,
CHarom), 128.04 (CHarom), 128.44 (CHarom), 128.88 (2C,
CHarom), 129.97 (2C, CHarom), 133.74 (CHarom), 154.18
(N=CH), 118.44, 123.87, 136.13, 141.51, 155.75,
157.85, 158.03, 172.19 (C=O). Found, %: C 72.56;
H 4.92; N 6.55. C H N O . Calculated, %: C 72.80;
1
3
2
3
2
3
3
Harom, J = 7.5 Hz), 6.99 t (1H, H , J = 7.5 Hz),
arom
3
7
(
.00 s (1H, 4-H), 7.30 d (2H, H , J = 8 Hz), 7.44 t
arom
25 20
2
4
3
3
1H, Harom, J = 7.5 Hz), 7.72 d (2H, H , J = 8 Hz),
H 4.89; N 6.79.
E)-2-Ethoxybenzaldehyde O-[5-(2,5-dimethyl-
phenyl)-1,2-oxazole-3-carbonyl] oxime (29). Yield
arom
3
8
.05 d (1H, Harom, J = 7.5 Hz), 9.07 s (1H, N=CH).
C NMR spectrum, δ , ppm: 14.94 (CH Me),
1.70 (Me), 64.27 (CH ), 99.84 (C ), 112.14 (CHarom),
20.87 (CHarom), 126.08 (2C, CHarom), 127.82 (CHarom),
30.01 (2C, CHarom), 133.76 (CHarom), 154.41 (N=CH),
18.12, 123.94, 141.55, 155.87, 157.94, 158.37,
72.25 (C=O). Found, %: C 68.26; H 5.25; N 7.64.
(
1
3
C
2
4
2
1
1
1
1
–1
2
7
3
3%, mp 128–130°C. IR spectrum, ν, cm : 3168,
143, 3088, 3043, 3022, 2981, 2928, 2897, 2867
(C–H), 1752 (C=O), 1610, 1597, 1585, 1501, 1492,
453 (C=C, C=N), 1256, 1222, 1147 (C–O–C).
1
1
3
H NMR spectrum, δ, ppm: 1.44 t (3H, CH Me, J =
2
C H N O . Calculated, %: C 68.56; H 5.18; N 8.00.
2
0
18
2
4
6.9 Hz), 2.37 s (3H, Me), 2.48 s (3H, Me), 4.08 q (2H,
3
3
M 350.37.
E)-2-Butoxybenzaldehyde O-[5-(4-methylphe-
nyl)-1,2-oxazole-3-carbonyl] oxime (27). Yield 75%,
mp 96–97°C. IR spectrum, ν, cm : 3137, 3075, 3034,
960, 2931, 2872 (C–H), 1750 (C=O), 1613, 1599,
507, 1491, 1445, 1410 (C=C, C=N), 1258, 1224,
127 (C–O–C). H NMR spectrum, δ, ppm: 0.97 t (3H,
CH Me, J = 7.4 Hz), 1.50 sext (2H, CH Me,
J = 7.4 Hz), 1.79 q (2H, OCH CH , J = 7 Hz),
.41 s (3H, Me), 3.99 t (2H, OCH Me, J = 6.4 Hz),
.88 d (1H, Harom, J = 7.4 Hz), 6.98 t (1H, Harom,
J = 7.5 Hz), 7.00 s (1H, 4-H), 7.29 d (2H, Harom,
J = 8 Hz), 7.44 t (1H, H , J = 7.5 Hz), 7.71 d (2H,
CH Me, J = 6.9 Hz), 6.89 d (1H, H , J = 8.4 Hz),
2
arom
3
6
(
.94 s (1H, 4-H), 6.98 t (1H, H , J = 7.4 Hz), 7.19 s
2H, Harom), 7.43 t (1H, H , J = 7.8 Hz), 7.57 s (1H,
(
arom
3
arom
3
–
1
Harom), 8.04 d (1H, H , J = 7.6 Hz), 9.06 s (1H,
arom
1
3
N=CH). C NMR spectrum, δ , ppm: 14.86 (CH Me),
2
1
1
C
2
4
2
1
1
1
1
0.94 (Me), 21.07 (Me), 64.19 (CH ), 103.20 (C ),
2
1
12.08 (CHarom), 120.78 (CHarom), 127.72 (CHarom),
29.00 (CHarom), 131.57 (CHarom), 131.59 (CHarom),
33.71 (CHarom), 154.31 (N=CH), 118.01, 125.79,
33.38, 136.10, 155.50, 157.90, 158.29, 172.16 (C=O).
3
2
2
3
3
2
2
3
2
2
3
Found, %: C 69.10; H 5.59; N 7.33. C H N O .
6
21 20
2
4
3
Calculated, %: C 69.22; H 5.53; N 7.69.
3
3
arom
(E)-2-Butoxybenzaldehyde O-[5-(2,5-dimethylphe-
nyl)-1,2-oxazole-3-carbonyl] oxime (30). Yield 76%,
3
3
Harom, J = 8 Hz), 8.06 d (1H, H , J = 7.7 Hz),
arom
1
3
–1
9
.04 s (1H, N=CH). C NMR spectrum, δ , ppm:
mp 90–92°C. IR spectrum, ν, cm : 3176, 3132, 3074,
C
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

SYNTHESIS OF 5-ARYLISOXAZOLE-3-CARBOXYLATES
39
3
1
1
032, 3002, 2959, 2933, 2871 (C–H), 1755 (C=O),
610, 1599, 1571, 1505, 1491, 1454 (C=C, C=N),
(E)-4-[(2-Ethoxybenzylidene)amino]phenyl
5-phenyl-1,2-oxazole-3-carboxylate (33). Yield 83%,
mp 139–140°C. IR spectrum, ν, cm : 3143, 3127,
1
–1
255, 1222, 1146 (C–O–C). H NMR spectrum,
3
δ, ppm: 0.99 t (3H, CH Me, J = 7.4 Hz), 1.50 sext
3076, 3063, 3050, 3038, 2988, 2934, 2888, 2854
(C–H), 1750 (C=O), 1621, 1603, 1590, 1570, 1501,
1491, 1477, 1459, 1447, 1437 (C=C, C=N), 1242,
2
3
(
2H, CH Me, J = 7.4 Hz), 1.80 q (2H, OCH CH ,
J = 7 Hz), 2.37 s (3H, Me), 2.48 s (3H, Me),
2
2
2
3
3
1
4
.02 t (2H, OCH Me, J = 6.4 Hz), 6.92 d (1H, Harom,
1182, 1123 (C–O–C). H NMR spectrum, δ, ppm:
2
3
3
J = 8.4 Hz), 6.95 s (1H, 4-H), 6.98 t (1H, Harom
J = 7.5 Hz), 7.19 s (2H, Harom), 7.43 t (1H, Harom
J = 7.9 Hz), 7.57 s (1H, Harom), 8.05 d (1H, Harom,
J = 7.7 Hz), 9.06 s (1H, N=CH). C NMR spectrum,
,
,
1.46 t (3H, Me, J = 7 Hz), 4.12 q (2H, OCH ,
2
3
3
3
3
3
J = 7 Hz), 6.94 d (1H, H , J = 8.2 Hz), 7.03 t (1H,
Harom, J = 7.5 Hz), 7.07 s (1H, 4-H), 7.29 m (4H,
Harom), 7.43 t (1H, Harom, J = 7.4 Hz), 7.50 m (3H,
arom
3
13
3
δ , ppm: 13.93 (CH Me), 19.40 (CH Me), 20.96 (Me),
Harom), 7.85 m (2H, Harom), 8.16 d (1H, Harom,
C
2
2
3
13
2
1
1.08 (Me), 31.26 (OCH CH ), 68.33 (OCH ),
03.25 (C ), 112.09 (CHarom), 120.74 (CHarom), 127.77
J = 7.7 Hz), 8.96 s (1H, N=CH). C NMR spec-
2
2
2
4
4
trum, δ , ppm: 14.93 (Me), 64.12 (OCH ), 100.40 (C ),
C
2
(
(
1
1
CHarom), 129.02 (CHarom), 131.58 (CHarom), 131.60
CHarom), 133.72 (CHarom), 154.22 (N=CH), 118.03,
25.80, 133.40, 136.12, 155.52, 157.96, 158.44,
72.18 (C=O). Found, %: C 69.98; H 6.07; N 6.75.
112.17 (CHarom), 120.83 (CHarom), 122.06 (2C, CHarom),
122.23 (2C, CHarom), 126.09 (2C, CHarom), 127.61
(CHarom), 129.32 (2C, CHarom), 131.09 (CHarom), 133.02
(CHarom), 157.30 (N=CH), 124.64, 126.57, 147.94,
151.27, 156.61, 158.73, 159.15, 172.24 (C=O).
Found, %: C 72.94; H 4.80; N 6.62. Mass spectrum:
C H N O . Calculated, %: C 70.39; H 6.16; N 7.14.
2
3
24
2
4
(E)-2-(Benzyloxy)benzaldehyde O-[5-(2,5-di-
+
m/z 412 [M] . C H N O . Calculated, %: C 72.80;
2
5
20
2
4
methylphenyl)-1,2-oxazole-3-carbonyl] oxime (31).
Yield 77%, mp 103–105°C. IR spectrum, ν, cm :
–
1
H 4.89; N 6.79. M 412.44.
3
2
1
180, 3140, 3076, 3058, 3033, 2956, 2920, 2865,
854 (C–H), 1751 (C=O), 1610, 1599, 1574, 1496,
490, 1448 (C=C, C=N), 1256, 1225, 1107 (C–O–C).
(E)-4-[(2-Ethoxybenzylidene)amino]phenyl
5-(4-methylphenyl)-1,2-oxazole-3-carboxylate (34).
–
1
Yield 86%, mp 140–141°C. IR spectrum, ν, cm :
3136, 3100, 3055, 3040, 2983, 2921, 2897, 2854
(C–H), 1753 (C=O), 1615, 1600, 1587, 1575, 1501,
1487, 1473, 1446, 1411 (C=C, C=N), 1220, 1183, 1100
1
H NMR spectrum, δ, ppm: 2.38 s (3H, Me), 2.49 s
(
3H, Me), 5.13 s (2H, PhCH ), 6.94 s (1H, 4-H),
2
7
.03 m (2H, Harom), 7.21 s (2H, Harom), 7.37 m (1H,
1
Harom), 7.44 m (5H, Harom), 7.58 s (1H, Harom), 8.09 d
(C–O–C). H NMR spectrum, δ, ppm: 1.46 t (3H,
3
13
3
(
1H, Harom, J = 7.6 Hz), 9.09 s (1H, N=CH). C NMR
CH Me, J = 6.9 Hz), 2.42 s (3H, Me), 4.12 q (2H,
2
3
3
spectrum, δ , ppm: 20.95 (Me), 21.09 (Me), 70.60
CH , J = 6.9 Hz), 6.94 d (1H, H , J = 8.3 Hz),
7.01 s (1H, 4-H), 7.03 t (1H, Harom, J = 7.5 Hz),
7.29 m (6H, Harom), 7.43 t (1H, H , J = 7.4 Hz),
7.73 d (2H, H , J = 7.7 Hz), 8.15 d (1H, Harom,
C
2
arom
4
3
(
(
(
(
PhCH ), 103.19 (C ), 112.59 (CHarom), 121.26
2
3
CHarom), 127.70 (2C, CHarom), 128.00 (CHarom), 128.41
CHarom), 128.84 (2C, CHarom), 129.01 (CHarom), 131.57
2C, CHarom), 133.72 (CHarom), 154.16 (N=CH),
arom
3
arom
3
13
J = 7.7 Hz), 8.96 s (1H, N=CH). C NMR spectrum,
1
1
18.38, 125.78, 133.38, 136.08, 136.10, 155.44,
57.88, 157.99, 172.13 (C=O). Found, %: C 73.19;
δ , ppm: 14.93 (CH Me), 21.67 (Me), 64.12 (CH ),
C
2
2
4
99.80 (C ), 112.17 (CHarom), 120.83 (CHarom), 122.07
(2C, CHarom), 122.23 (2C, CHarom), 126.03 (2C, CHarom),
127.61 (CHarom), 129.99 (2C, CHarom), 133.02 (CHarom),
H 5.21; N 6.22. C H N O . Calculated, %: C 73.23;
H 5.20; N 6.57.
2
6
22
2
4
1
1
57.31 (N=CH), 123.89, 124.64, 141.55, 147.97,
Schiff base esters 33–35 (general procedure).
Schiff base 32 was added to a solution of 2 mmol of
51.24, 156.55, 158.81, 159.15, 172.45 (C=O). Mass
+
spectrum: m/z 426 [M] . Found, %: C 73.28; H 5.40;
N 6.41. C H N O . Calculated, %: C 73.23; H 5.20;
N 6.57. M 426.46.
5
-aryl-1,2-oxazole-3-carbonyl chloride and 2.1 mmol of
2
6
22
2
4
anhydrous triethylamine in 25 mL of anhydrous meth-
ylene chloride, and the mixture was stirred for 3 h at
30°C. The mixture was washed with water (3×50 mL),
(E)-4-[(2-Ethoxybenzylidene)amino]phenyl
the organic layer was separated and dried over sodium
sulfate, the solvent was distilled off under reduced
pressure, and 10 mL of anhydrous methanol was added
to the residue. The precipitate was filtered off, washed
with cold methanol, and dried under reduced pressure.
5-(2,5-dimethylphenyl)-1,2-oxazole-3-carboxylate
–
1
(35). Yield 78%, mp 91–92°C. IR spectrum, ν, cm :
3195, 3072, 3038, 2976, 2923, 2854 (C–H), 1746
(C=O), 1619, 1602, 1593, 1578, 1501, 1488, 1462
1
(C=C, C=N), 1227, 1183, 1103 (C–O–C). H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

4
0
PETKEVICH et al.
3
spectrum, δ, ppm: 1.47 t (3H, CH Me, J = 7 Hz),
172.03 (C=O). Found, %: C 72.58; H 5.47; N 6.68.
C H N O . Calculated, %: C 72.45; H 5.35; N 6.76.
2
2
.40 s (3H, Me), 2.52 s (3H, Me), 4.13 q (2H, CH ,
J = 7 Hz), 6.95 d (1H, H , J = 8.3 Hz), 6.97 s (1H,
-H), 7.03 t (1H, Harom, J = 7.5 Hz), 7.22 s (2H,
Harom), 7.30 m (4H, Harom), 7.43 t (1H, Harom, J =
.5 Hz), 7.61 s (1H, Harom), 8.15 d (1H, H , J =
.7 Hz), 8.96 s (1H, N=CH). C NMR spectrum, δ ,
2
25 22
2
4
3
3
arom
3
4-[(2-Ethoxybenzyl)amino]phenyl 5-(4-methyl-
4
phenyl)-1,2-oxazole-3-carboxylate (37). Yield 94%,
3
–1
mp 125–126°C. IR spectrum, ν, cm : 3402 (NH),
3
7
7
3133, 3063, 3041, 2979, 2926, 2868 (C–H), 1743
(C=O), 1606, 1593, 1518, 1498, 1473, 1453, 1440,
arom
1
3
C
ppm: 14.97 (CH Me), 21.02 (Me), 21.13 (Me), 64.15
1409 (C=C, C=N), 1244, 1192, 1110 (C–O–C).
2
4
1
(
CH ), 103.32 (C ), 112.19 (CHarom), 120.86 (CHarom),
H NMR spectrum, δ, ppm: 1.45 t (3H, CH Me,
2
2
3
1
22.09 (2C, CHarom), 122.26 (2C, CHarom), 127.64
J = 6.9 Hz), 2.43 s (3H, Me), 4.09 q (2H, CH
2
Me,
N), 6.68 d (2H, Harom
J = 8.4 Hz), 6.91 m (2H, Harom), 6.98 s (1H, 4-H),
3
3
(
(
CHarom), 129.10 (CHarom), 131.63 (CHarom), 131.67
CHarom), 133.03 (CHarom), 157.33 (N=CH), 124.68,
J = 6.9 Hz), 4.37 s (2H, CH
2
,
3
1
1
25.90, 133.44, 136.20, 147.99, 151.28, 156.29,
7.07 d (2H, Harom, J = 8.4 Hz), 7.25 t (1H, Harom,
3
58.91, 159.17, 172.47 (C=O). Mass spectrum:
J = 7.4 Hz), 7.32 m (4H, Harom, NH), 7.73 d (2H,
3
13
+
Harom, J = 8.5 Hz). C NMR spectrum, δ , ppm: 15.08
m/z 440 [M] . Found, %: C 73.77; H 5.52; N 6.29.
C
(
9
1
CH Me), 21.65 (Me), 43.95 (CH N), 63.62 (CH Me),
9.80 (C ), 111.30 (CHarom), 113.44 (2C, CHarom),
C H N O . Calculated, %: C 73.62; H 5.49; N 6.36.
2 2 2
2
7
24
2
4
4
M 440.49.
20.51 (CHarom), 121.95 (2C, CHarom), 126.01 (2C
,
Reduction of Schiff base esters 33–35 (general
procedure). Glacial acetic acid, 0.5 mL (9 mmol), was
added dropwise to a suspension of 0.12 g (3 mmol)
of sodium tetrahydridoborate in 40 mL of anhydrous
benzene, the mixture was stirred for 20 min, and
CHarom), 128.45 (CHarom), 128.98 (CHarom), 129.96 (2C,
CHarom), 123.99, 127.19, 141.41, 141.43, 146.98,
1
56.80, 156.86, 159.26, 172.24 (C=O). Found, %:
C 72.95; H 5.61; N 6.51. C H N O . Calculated, %:
2
6
24
2
4
C 72.88; H 5.65; N 6.54.
-[(2-Ethoxybenzyl)amino]phenyl 5-(2,5-dimeth-
1
.5 mmol of ester 33–35 was added. The mixture was
4
stirred for 4 h at 20°C, treated with 50 mL of water,
and stirred for 20 min, and the organic phase was
separated, washed with 50 mL of water, and dried over
sodium sulfate. The solvent was distilled off under
reduced pressure, 10 mL of anhydrous methanol was
added to the residue, and the precipitate was filtered
off, washed with cold methanol, and dried under
reduced pressure.
ylphenyl)-1,2-oxazole-3-carboxylate (38). Yield 82%,
–1
mp 92–93°C. IR spectrum, ν, cm : 3417 (NH), 3168,
3
(
1
138, 3063, 3036, 2978, 2926, 2872 (C–H), 1747
C=O), 1611, 1602, 1589, 1576, 1515, 1494, 1474,
454, 1422 (C=C, C=N), 1234, 1195, 1115 (C–O–C).
1
H NMR spectrum, δ, ppm: 1.47 t (3H, CH Me,
J = 7 Hz), 2.41 s (3H, Me), 2.51 s (3H, Me), 4.10 q
2
3
3
(
2H, CH Me, J = 7 Hz), 4.38 s (2H, CH N), 6.70 d
2
2
3
3
4
-[(2-Ethoxybenzyl)amino]phenyl 5-phenyl-1,2-ox-
(2H, Harom, J = 8.8 Hz), 6.90 d (1H, Harom, J = 8 Hz),
6.94 t (1H, Harom, J = 7.5 Hz), 6.96 s (1H, 4-H), 7.11 d
(2H, Harom, J = 8.8 Hz), 7.25 m (4H, Harom, NH),
3
azole-3-carboxylate (36). Yield 88%, mp 144–145°C.
–
1
3
IR spectrum, ν, cm : 3419 (NH), 3161, 3148, 3134,
3
7
.34 d (1H, Harom, J = 7.4 Hz), 7.62 s (1H, Harom).
3
1
064, 3034, 2984, 2920, 2867 (C–H), 1740 (C=O),
611, 1599, 1590, 1573, 1523, 1492, 1473, 1453,
1
3
C NMR spectrum, δ , ppm: 14.96 (CH Me), 20.84
C
2
(
1
1
Me), 20.96 (Me), 43.75 (CH N), 63.48 (CH Me),
03.16 (C ), 111.16 (CHarom), 113.32 (2C, CHarom),
20.38 (CHarom), 121.81 (2C, CHarom), 128.30 (CHarom),
1
447, 1439 (C=C, C=N), 1236, 1191, 1124 (C–O–C).
2 2
4
1
3
H NMR spectrum, δ, ppm: 1.46 t (3H, Me, J = 7 Hz),
4
3
.10 q (2H, CH Me, J = 7 Hz), 4.37 s (2H, CH N),
2
2
3
128.78 (CHarom), 128.89 (CHarom), 131.46 (2C, CHarom),
125.78, 127.07, 133.26, 136.00, 141.26, 146.88,
156.39, 156.70, 159.20, 172.08 (C=O). Found, %:
C 73.33; H 5.95; N 6.24. C H N O . Calculated, %:
6
.69 d (2H, Harom, J = 8.9 Hz), 6.91 d (1H, Harom,
3
3
J = 8.2 Hz), 6.94 t (1H, H , J = 7.5 Hz), 7.04 s
arom
3
(
1H, 4-H), 7.08 d (2H, H , J = 8.9 Hz), 7.25 t (1H,
arom
3
3
2
7
26
2
4
Harom, J = 7.7 Hz), 7.33 d (1H, H , J = 7.3 Hz),
arom
C 73.28; H 5.92; N 6.33.
7
.38 s (1H, NH), 7.51 m (3H, Harom), 7.85 m (2H,
1
3
Harom). C NMR spectrum, δ , ppm: 15.08 (Me),
4
C
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4
3.93 (CH N), 63.61 (CH Me), 100.39 (C ), 111.29
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(
(
CHarom), 113.44 (2C, CHarom), 120.50 (CHarom), 121.93
2C, CHarom), 126.06 (2C, CHarom), 128.45 (CHarom),
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. Ryng, S., Sonnenberg, Z., and Zimecki, M., Arch. Im-
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1
1
28.97 (CHarom), 129.28 (2C, CHarom), 130.99 (CHarom),
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