Esters of benzoic, 5-arylisoxazole-3-carboxylic and 4,5- dichloroisothiazole-3-carboxylic acids

Article abstract of DOI:10.1134/S107036321406019X

The method of synthesis was developed of esters of benzoic, 2-chlorobenzoic, 5-phenylisoxazole-3-carboxylic, 5-tolylisoxazole-3-carboxylic, and 4,5-dichloroisothiazole-3-carboxylic acids with some aliphatic and substituted aromatic alcohols. The latter were obtained by reduction of aldehydes used in perfumery.

Full text of DOI:10.1134/S107036321406019X

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 6, pp. 1179–1185. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © E.A. Dikusar, V.I. Potkin, N.A. Zhukovskaya, M.Yu. Murashova, S.K. Petkevich, A.V. Kletskov, R.M. Zolotar’, O.P. Chepik, 2014,
published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 6, pp. 1000–1006.
Esters of Benzoic, 5-Arylisoxazole-3-carboxylic
and 4,5-Dichloroisothiazole-3-carboxylic Acids
E. A. Dikusara, V. I. Potkina, N. A. Zhukovskayaa, M. Yu. Murashovaa,
S. K. Petkevicha, A. V. Kletskova, R. M. Zolotar’b, and O. P. Chepikb
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 Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
Received August 26, 2013
Abstract—The method of synthesis was developed of esters of benzoic, 2-chlorobenzoic, 5-phenylisoxazole-3-
carboxylic, 5-tolylisoxazole-3-carboxylic, and 4,5-dichloroisothiazole-3-carboxylic acids with some aliphatic
and substituted aromatic alcohols. The latter were obtained by reduction of aldehydes used in perfumery.
Keywords: esters of carboxylic acids, aldehydes, alcohols
DOI: 10.1134/S107036321406019X
Aliphatic and substituted aromatic aldehydes such
as lauric aldehyde (n-dodecanal) I, jasmorange [2-
methyl-3-(4-methylphenyl)propanal] II, cyclamen al-
dehyde [2-(4-isopropylbenzyl)propanal] III, anisic al-
dehyde (4-dehydromethoxybenzaldehyde) IV, veratric
aldehyde (3,4-dimethoxybenzaldehyde) V, 4-(n-hexyl-
oxy)-3-methoxybenzylaldehyde VI, 4-benzyloxy-3-
methoxybenzaldehyde VII, 4-(n-hexyloxy)-3-ethoxy-
benzaldehyde VIII, 4-(n-octyloxy)-3-ethoxybenzal-
dehyde IX, 3,4-di(n-butyloxy)benzaldehyde X are
present in essential oils of some plants. They are widely
used in the perfume industry as odoriferous substances
[1–3], and may also be used as starting compounds
accessible for chemical modification for the purpose of
synthesis of biologically active compounds [4–6].
5-tolylisoxazole-3-carboxylic XXIV or 4,5-dichloro-
isothiazole-3-carboxylic acid XXV in ahydrous diethyl
ether in the presence of triethylamine afforded the
corresponding esters XXVI–LVI with 88–92% yields
(Scheme 1).
Physicochemical characteristics of alcohols XI,
XIV, XV have been reported in [7]. The composition
and structure of the rest of the synthesized compounds
XII, XIII, XVI–XX, XXVI–LVI was proved by
elemental analysis, gas chromatography-mass spectro-
metry, IR and 1H NMR spectroscopy data (Tables 1, 2).
The resulting compounds are colorless or lightly
colored crystalline solids or liquids which did not
require additional purification and did not contain
impurities of the starting compounds.
The aim of this work was to develop a method for
the synthesis of esters of benzoic, 2-chlorobenzoic, 5-
phenylisoxazole-3carboxylic, 5-tolylisoxazole-3-carboxylic,
and 4,5-dichloroisothiazole-3-carboxylic acids XXI–
XXV with a series of aliphatic and substituted aro-
matic alcohols XI–XX obtained by reduction of the
available aldehydes I–X. The latter were converted to
alcohols XI–XX by the reduction with sodium boro-
hydride in 2-propanol with 68–84% yields. The esteri-
fication of aliphatic and substituted aromatic alcohols
XI–XX with chlorides of benzoic XXI, 2-chloro-
benzoic XXII, 5-phenylisoxazole-3-carboxylic XXIII,
Due to the presence of aromatic and heterocyclic
moieties in the molecules esters XXVI–LVI are of
interest for the study of biological activity to detect the
correlation between the biological activity and
organoleptic analysis of odors and flavors of the
starting aldehydes I–X. This is one of new and
promising approaches to the creation of effective drugs
for medical and agricultural purposes [8].
EXPERIMENTAL
The IR spectra were recorded on a Nicolet Protégé-
460 FTIR spectrophotometer from KBr pellets or thin
1179

1180
DIKUSAR et al.
Scheme 1.
R2C(O)Cl (XXI_XXV), Et3N
NaBH4
R1CH2OC(O)R2
R1CHO
R1CH2OH
i-PrOH
Et2O
XI_XX
XXVI_LVI
I_X
(II, XII, XXIX_XXXII),
(I, XI, XXVI_XXVIII),
Me
R = Me(CH2)10
Me2HC
Me
_
(IV, XIV, XXXVI_XXXIX),
Me
MeO
(III, XIII, XXXIII XXXV),
(V, XV, XL_XLII),
(VI, XVI, XLIII_XLVI),
(VII, XVII, XLVII_XLIX),
OMe
OMe
OMe
OC6H13
OMe
OCH2Ph
(X, XX, LIV_LVI);
(VIII, XVIII, L, LI),
(IX, XIX, LII, LIII),
OEt
OEt
OC8H17
OBu
OC6H13
OBu
Cl
R2 =
(XXII, XLIV),
(XXI, XXIX, XXXVI, XL, XLIII, XLVII, LIV),
N
(XXIII, XXVI, XXX, XXXIII, XXXVII, XLI, XLV, XLVIII, L, LII, LV),
O
(XXIV, XXVII, XXXI, XXXIV, XXXVIII),
N
Me
Cl
O
N
(XXV, XXVIII, XXXII, XXXV, XXXIX, XLII, XLVI, XLIX, LI, LIII, LVI).
Cl
S
All alkoxy substituents (BuO, C6H13O and C8H17O) have linear structure.
1
films. The H NMR spectra were registered on a
Bruker Avance-500 spectrometer from 5% solutions in
CDCl3. Mass spectra were obtained on a Hewlett
Packard 5890/5972 instrument operating at electron
impact ionization mode with ionizing electrons energy
of 70 eV; capillary column HP-5MS 30 m × 0.25 mm,
phase (5% PhMe Silicone) 0.25 microns, the
evaporator temperature 250°C.
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Table 2. IR and 1Н NMR spectral data of compounds XII–XX, XXVI–LVI
1183
Comp. no.
IR spectrum, ν, cm–1
1Н NMR spectrum, δ, ppm (J, Hz)
XII
3343 (ОН); 1515 (Ar); 1035 (C–O)
0.94 d (3Н, Me, J 6.6), 2.36 s (3Н, MeС6Н4), 3.51
d (2Н, СН2О, J 6.6), 7.11 s (4Н, С6Н4)
XIII
3333 (ОН); 1512 (Ar); 1035 (C–O)
0.95 d (3Н, Me, J 6.5), 1.29 d (6Н, Me2C, J 6.3),
3.52 d (2Н, СН2О, J 5.6), 7.16 s (4Н, С6Н4)
XIV
XV
3384 (ОН); 1612, 1514 (Ar); 1251, 1180, 1033 (C–O)
3.82 s (3Н, Me), 4.63 s (2Н, СН2О)
3477, 3386 (ОН); 1608, 1594, 1516 (Ar); 1262, 1237, 3.71 s (6Н, 2Me), 4.42 s (2Н, СН2О)
1155, 1138, 1027(C–O)
XVI
3418 (OH); 1608, 1592, 1515 (Ar); 1263, 1236, 1159, 0.91 t (3Н, Me, J 6.6), 3.88 s (3H, MeO), 4.61 d
1138, 1036 (C–O)
3410 (OH); 1609, 1590, 1515 (Ar); 1260, 1235, 1160, 3.89 s (3H, MeO), 4.60 d (2Н, СН2О, J 5.8), 5.15 s
1134, 1032, 1004 (C–O) (2Н, PhСН2О)
(2Н, СН2О, J 5.8)
XVII
XVIII
XIX
3405 (OH); 1607, 1591, 1514 (Ar); 1261, 1234, 1164, 0.90 t (3Н, Me, J 6.5), 4.44 s (2Н, СН2О)
1137, 1045 (C–O)
3335, 3252 (OH); 1606, 1591, 1517 (Ar); 1258, 1234, 0.89 t (3Н, Me, J 6.5), 4.60 s (2Н, СН2О)
1136, 1041 (C–O)
XX
3414 (OH); 1608, 1592, 1515 (Ar); 1263, 1236, 1165, 0.98 t (6Н, 2Me, J 6.4), 4.00 t (4Н, 2СН2О, J 6.3),
1136, 1066, 1025 (C–O)
3150 (CHisoxazole); 1737, 1728 (C=O); 1611, 1589, 1571 0.95 t (3Н, Me, J 6.4), 4.42 t (2Н, СН2О, J 5.8),
(Ar); 1449 (C=N); 1246, 1144 (C–O) 6.92 s (1H, CHisoxazole
3138 (CHisoxazole); 1728 (C=O); 1616 (Ar); 1449 (C=N); 0.96 t (3Н, Me, J 6.4), 3.93 s (3H, Me), 4.42 t (2Н,
4.56 d (2Н, СН2О, J 5.9)
XXVI
XXVII
)
1245, 1140 (C–O)
СН2О,
J 5.8), 7.02 s (1H, CHisoxazole
)
XXVIII
XXIX
1728 (C=O); 1228, 1084 (C–O)
0.95 t (3Н, Me, J 6.4), 4.42 t (2Н, СН2О, J 5.8)
1720 (C=O); 1600, 1585, 1515 (Ar); 1274, 1213, 1112 (C– 1.06 d (3Н, Me, J 6.6), 2.35 s (3Н, MeС6Н4), 4.23
O) d (2Н, СН2О, J 5.6), 7.12 s (4Н, С6Н4)
3134 (CHisoxazole); 1729 (C=O); 1612, 1585, 1572, 1514 1.04 d (3Н, Me, J 6.6), 2.32 s (3Н, MeС6Н4), 4.28
XXX
(Ar); 1254, 1146, 1005 (C–O)
d (2Н, СН2О, J 5.6), 6.82 s (1H, CHisoxazole), 7.10 s
(4Н, С6Н4)
XXXI
3139 (CHisoxazole); 1733 (C=O); 1616, 1595, 1574, 1513 1.04 d (3Н, Me, J 6.6), 2.32 s and 2.43 s (6Н,
(Ar); 1240, 1140, 1005 (C–O)
MeС6Н4), 4.27 d (2Н, СН2О, J 5.6), 6.83 s (1H,
CHisoxazole), 7.10 s (4Н, С6Н4)
ХХXII
1735 (C=O); 1515 (Ar); 1223, 1084, 986 (C–O)
1.04 d (3Н, Me, J 6.6), 2.32 s (3Н, MeС6Н4), 4.32
d (2Н, СН2О, J 5.6), 7.09 s (4Н, С6Н4)
XXXIII
1732 (C=O); 1612, 1591, 1573, 1512 (Ar); 1239, 1140, 1.05 d (3Н, Me, J 6.5), 1.24 d (6Н, Me2C, J 6.9),
1004
4.29 d (2Н, СН2О, J 5.6), 7.14 s (4Н, С6Н4)
(C–O)
XXXIV
3140 (CHisoxazole); 1733 (C=O); 1615, 1595, 1572, 1511 1.05 d (3Н, Me, J 6.5), 1.24 d (6Н, Me2C, J 6.3),
(Ar); 1240, 1139, 1004 (C–O)
2.43 s (3Н, MeС6Н4), 4.27 d (2Н, СН2О, J 5.6),
6.85 s (1H, CHisoxazole), 7.14 s (4Н, С6Н4)
XXXV
1736 (C=O); 1512 (Ar); 1223, 1084, 986 (C–O)
1.02 d (3Н, Me, J 6.5), 1.24 d (6Н, Me2C, J 6.3),
4.24 d (2Н, СН2О, J 5.6), 7.11 s (4Н, С6Н4)
XXXVI
1717 (C=O); 1613, 1601, 1585, 1515 (Ar); 1272, 1249, 3.83 s (3H, Me), 5.32 s (2Н, СН2О)
1175, 1109, 1070, 1035, 1027 (C–O)
XXXVII 3129 (CHisoxazole); 1727 (C=O); 1613, 1571, 1516 (Ar); 3.83 s (3H, Me), 5.39 s (2Н, СН2О), 6.91 s (1H,
1257, 1231, 1182, 1137, 1032, 1005, 979 (C–O) CHisoxazole
)
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DIKUSAR et al.
Table 2. (Contd.)
Comp. no.
IR spectrum, ν, cm–1
1Н NMR spectrum, δ, ppm (J, Hz)
XXXVIII 3138 (CHisoxazole); 1727 (C=O); 1613, 1515 (Ar); 1256, 3.82 s (3H, MeO), 3.94 s (3H, Me), 5.38 s (2Н,
1232, 1179, 1135, 1035, 1006, 980 (C–O) СН2О), 6.86 s (1H, CHisoxazole
)
XXXIX
1727 (C=O); 1614, 1582, 1516 (Ar); 1239, 1228, 1176, 3.82 s (3H, Me), 5.38 s (2Н, СН2О)
1085, 1034, 971 (C–O)
XL
1718 (C=O); 1598, 1518 (Ar); 1266, 1213, 1161, 1141, 3.90 s and 3.91 s (6H, 2Me), 5.31 s (2Н, СН2О)
1109, 1070, 1028 (C–O)
XLI
3130 (CHisoxazole); 1730 (C=O); 1611, 1595, 1573, 1525 3.90 s and 3.92 s (6H, 2Me), 5.39 s (2Н, СН2О),
(Ar); 1241, 1166, 1136, 1037, 1022, 1001 (C–O)
6.92 s (1H, CHisoxazole)
XLII
XLIII
XLIV
XLV
XLVI
XLVII
XLVIII
XLIX
L
1724 (C=O); 1593, 1519 (Ar); 1256, 1225, 1138, 1092, 3.89 s (6H, 2Me), 5.37 s (2Н, СН2О)
1031, 1012, 969 (C–O)
1719 (C=O); 1595, 1516 (Ar); 1267, 1238, 1213, 1164, 0.91 t (3Н, Me, J 6.6), 3.87 s (3H, MeO), 5.30 s
1140, 1109, 1070, 1038 (C–O)
1729 (C=O); 1608, 1592, 1517 (Ar); 1290, 1266, 1249, 0.89 t (3Н, Me, J 6.6), 3.85 s (3H, MeO), 5.29 s
1164, 1139, 1121, 1075, 1049, 1040 (C–O) (2Н, СН2О)
3130 (CHisoxazole); 1727 (C=O); 1607, 1592, 1573, 1518 0.88 t (3Н, Me, J 6.6), 3.90 s (3H, MeO), 5.38 s
(Ar); 1274, 1253, 1234, 1138, 1027, 993 (C–O) (2Н, СН2О), 6.92 s (1H, CHisoxazole
1731 (C=O); 1593, 1519 (Ar); 1260, 1217, 1164, 1139, 0.90 t (3Н, Me, J 6.6), 3.88 s (3H, MeO), 5.37 s
1085, 1037, 1022, 993, 965 (C–O) (2Н, СН2О)
(2Н, СН2О)
)
1716 (C=O); 1595, 1515 (Ar); 1267, 1233, 1162, 1140, 3.92 s (6H, 2Me), 5.18 s and 5.31 s (4Н, СН2О)
1109, 1070, 1025 (C–O)
3132 (CHisoxazole); 1729 (C=O); 1609, 1590, 1581, 1518 3.93 s (6H, 2Me), 5.18 s and 5.37 s (4Н, СН2О),
(Ar); 1253, 1227, 1167, 1130, 1028, 1000, 986 (C–O)
6.92 s (1H, CHisoxazole)
1723 (C=O); 1608, 1593, 1517 (Ar); 1270, 1233, 1165, 3.90 s (6H, 2Me), 5.16 s and 5.36 s (4Н, СН2О)
1147, 1083, 1036, 1012, 973(C–O)
3133 (CHisoxazole); 1729 (C=O); 1608, 1591, 1573, 1519 0.91 t (3Н, Me, J 6.6), 5.36 s (2Н, СН2О), 6.92 s
(Ar); 1274, 1260, 1235, 1136, 1040, 995 (C–O)
(1H, CHisoxazole)
LI
1727 (C=O); 1608, 1594, 1522 (Ar); 1273, 1239, 1178, 0.91 t (3Н, Me, J 6.6), 5.36 s (2Н, СН2О)
1145, 1085, 1050, 973 (C–O)
LII
3133 (CHisoxazole); 1729 (C=O); 1606, 1592, 1573, 1518 0.91 t (3Н, Me, J 6.7), 5.36 s (2Н, СН2О), 6.92 s
(Ar); 1274, 1254, 1232, 1137, 1043, 999 (C–O)
(1H, CHisoxazole)
LIII
LIV
LV
1726 (C=O); 1607, 1594, 1523 (Ar); 1274, 1239, 1179, 0.89 t (3Н, Me, J 6.7), 5.36 s (2Н, СН2О)
1146, 1084, 1052, 972 (C–O)
1717, 1708 (C=O); 1594, 1515 (Ar); 1275, 1266, 1241, 0.99 t (6H, 2Me, J 6.3), 4.02 t (4H, 2CH2, J 6.1),
1179, 1140, 1118, 1068, 1026, 972 (C–O)
3133 (CHisoxazole); 1728 (C=O); 1608, 1591, 1576, 1520 0.98 t (6H, 2Me, J 6.3), 4.03 t (4H, 2CH2, J 6.1),
(Ar); 1276, 1258, 1235, 1135, 1069, 1024, 999, 978 (C–O) 5.36 s (2Н, СН2О), 6.92 s (1H, CHisoxazole
1726 (C=O); 1608, 1594, 1522 (Ar); 1275, 1241, 1178, 0.98 t (6H, 2Me, J 6.3), 4.01 t (4H, 2CH2, J 6.1),
5.29 s (2Н, СН2О)
)
LVI
1145, 1083, 1070, 1041, 972 (C–O)
5.35 s (2Н, СН2О)
Reduction of aldehydes I–X to alcohols XI–XX.
To a solution of 10 mmol of an appropriate aldehyde
I–X in 50 mL of anhydrous 2-propanol was added 10
mmol of sodium borohydride. The reaction mixture
was stirred for 4 h and then poured into water. The
reaction product was extracted with diethyl ether. The
extract was dried over sodium sulfate and evaporated.
The residue was purified by recrystallization from
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1185
2. Tkachyov, A.V., Issledovanie letuchikh veshchestv
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diethyl ether–hexane mixture (2 : 1) or by column
chromatography on silica gel (100–400 μm, eluent
diethyl ether–hexane, 2 : 1).
Synthesis of esters XXVI–LVI. To a mixture of
10 mmol of alcohol XI–XX and 10 mmol of anhydrous
triethylamine in 50 mL of anhydrous diethyl ether was
added in portions 10 mmol of the corresponding
carboxylic acid chloride XXI–XXV; a 1 : 1 : 1 ratio of
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maintained at 20–23°C for 24 h. The resulting
precipitate of triethylamine hydrochloride was filtered
off and washed with small amount of diethyl ether.
The ether solution was washed with water and 5%
aqueous sodium hydrogen carbonate. Then the solvent
was removed, the residue was purified by recrystal-
lization from diethyl ether–hexane (2 : 1) or by column
chromatography on silica gel (100–400 μm, diethyl
ether–hexane, 2 : 1).
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