4-ARYL-3-SUBSTITUTED FURANS

Article abstract of DOI:10.1135/cccc19942721

4-Aryl-3-substituted furans IIIa - IIId were prepared by Dield-Alder reaction of 4-phenyloxazole (I) with compounds IIa - IId, containing an activated triple bond, and subsequent thermal decomposition of the cycloadduct.

Full text of DOI:10.1135/cccc19942721

Short Communication
2721
4-ARYL-3-SUBSTITUTED FURANS
a
b
a
a
Jarmila STETINOVA , Jan LESKO , Miloslava DANDAROVA , Rudolf KADA
and Roman KOREN
a
a Department of Organic Chemistry,
Slovak Technical University, 812 37 Bratislava, The Slovak Republic
b Laboratory of Mass Specrometry,
Slovak Technical University, 812 37 Bratislava, The Slovak Republic
Received January 20, 1994
Accepted August 28, 1994
4-Aryl-3-substituted furans IIIa – IIId were prepared by Diels–Alder reaction of 4-phenyloxazole (I)
with compounds IIa – IId, containing an activated triple bond, and subsequent thermal decomposition
of the cycloadduct.
One of the most important synthetic methods leading to 3,4-disubstituted furans is the
Diels–Alder reaction of a suitable diene with a dienophile followed by the retrodiene
reaction.
In the original method1, the diene component is the less accessible furan and the
cycloadduct has to be catalytically hydrogenated prior to the thermal decomposition.
Because of this preparative complication there has been interest in alternative syntheses
based on 1,4-cycloadditions. One of them makes use of substituted 1,3-oxazoles such
as 4-methyloxazole2, and particularly 4-phenyloxazole3, as dienes which on reaction
with various alkynes and subsequent thermolysis afford furan derivatives. The cycload-
duct is decomposed at high temperature (about 200 °C) and, in the case of 4-phenylox-
azole (in contrast to its 4-methyl analogue), the decomposition takes place at
atmospheric pressure. 4-Phenyloxazole became a suitable precursor in syntheses of
other β-substituted furans that are otherwise accessible only with difficulty4–8
.
3-Benzoyl-4-(4-nitrophenyl)furan (IIIa), 3-benzoyl-4-(5-nitrofuryl)furan (IIIb), 3-(2-
furoyl)-4-phenylfuran (IIIc) and ethyl 4-(4-nitrophenyl)-3-furancarboxylate (IIId) were
obtained by Diels–Alder reaction of 4-phenyloxazole (I) with activated acetylenes IIa – IId
and subsequent decomposition of the cycloadduct at high temperature (Scheme 1).
The reaction was carried out by heating equimolar amounts of the reaction compo-
nents at 180 – 190 °C for 9 h in the atmosphere of an inert gas, in the presence of small
amounts of hydroquinone to prevent polymerization. The high boiling point of com-
pound I makes it possible to perform the cycloaddition as well as the subsequent de-
composition of the cycloadduct (not isolated) at atmospheric pressure. This represents
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

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Stetinova, Lesko, Dandarova, Kada, Koren:
an advantage because in syntheses involving 4-methyloxazole2 or other substituted oxa-
zoles9 the decomposition of the cycloadduct has to be made only at an elevated pressure.
After isolation, the reaction affords the 3,4-disubstituted furan and benzonitrile as the
side product. Saponification of ethyl ester IIId with potassium hydroxide in aqueous
alcohol gave the corresponding acid IIIe.
The structure of the 4-aryl-3-substituted furans IIIa – IIIe was confirmed by their
spectra and elemental analyses (Tables I – IV). The IR spectra od derivatives IIIa, IIIb,
IIId and IIIe exhibit, in addition to the characteristic bands (Table II), also bands at
1 515 – 1 545 cm−1 and 1 335 – 1 345 cm−1 due to the ν(NO2)as and ν(NO2)s vibrations,
respectively.
1
In the H NMR spectra (Table III) the protons of 3,4-disubstituted furan appear as
doublets with J(2,5) = 1.5 – 1.7 Hz. Signals of the H-2 protons in the region δ 7.88 – 8.45 are
shifted downfield compared with those of the H-5 protons (δ 7.56 – 8.16) as the result
of the presence of carbonyl in position 3.
The mass spectra of derivatives IIIa – IIIe (Table IV) display intense molecular ion
peaks which for IIIc, IIId and IIIe represent the base peaks. The presence of the benzoyl
group in compounds IIIa and IIIb is manifested by intense fragment ions m/z 105, m/z
77 and m/z 51. In the case of compound IIIc, the presence of a relatively intense peak
•
of (M − OH)+, m/z 221 (28%), is interesting. The furoyl group appears in the spectrum
as a fragment m/z 95 (37%) and its presence in the molecule gives rise to three
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Short Communication
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TABLE I
Physico-chemical data of 4-aryl-3-substituted furans IIIa – IIIe
Calculated/Found
% H
M.p., °C
Yield, %
Formula
(M.w.)
Compound
% C
% N
IIIa
IIIb
IIIc
IIId
IIIe
103 – 106
C17H11NO4
(293.3)
69.62
69.43
3.78
3.66
4.78
4.77
27
127 – 128
C15H9NO5
(283.2)
63.61
63.83
3.20
3.17
4.95
4.97
28
79 – 80
C15H10O3
(238.2)
75.62
75.11
4.23
4.06
–
–
24
90 – 92
C13H11NO5
(261.2)
59.77
59.61
4.25
4.26
5.36
5.38
31
220 – 221
C11H7NO5
(233.2)
56.66
56.14
3.03
2.89
6.01
5.84
76
TABLE II
IR (in KBr) and UV (in methanol, c 1 . 10−4 mol l−1) spectra of compounds IIIa – IIIe
IR spectrum, cm−1
UV spectrum
λmax, nm
Compound
ν(C=O)
ν(C−O−C)s
log ε
IIIa
IIIb
1 650
1 650
1 035
1 025
251
295
3.19
3.04
249
352
3.19
3.11
IIIc
IIId
IIIe
1 640
1 730
1 710
1 030
1 020
1 020
283
299
302
3.16
3.00
3.11
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Stetinova, Lesko, Dandarova, Kada, Koren:
TABLE III
1H NMR spectral data (δ, ppm; J, Hz) of 4-aryl-3-substituted furans IIIa – IIIe
Compounda
H-2
H-5
J(2,5)
Other signals
IIIa
7.88
7.71
1.5
8.00 – 7.80 m and 7.70 – 7.37 m, 2 H and 3 H
(benzoyl); 8.19 d and 7.57 d, 2 H and 2 H, J = 8.2
(4-nitrophenyl)
IIIb
IIIc
8.13
8.25
7.85
7.56
1.7
1.6
7.97 – 7.80 m and 7.70 – 7.40 m, 2 H and 3 H
(benzoyl); 7.36 and 7.28, AB system J = 3.7
(H-4 and H-3 of 5-nitro-2-furyl)
7.62 – 7.27 m, 5 H (phenyl); 7.61 dd, 1 H,
J(5,4) = 1.7, J(5,3) = 0.7 (H-5 of 2-furoyl); 7.21 dd, 1 H,
J(3,4) = 3.5, J(3,5) = 0.7 (H-3 of 2-furoyl);
6.54 dd, 1 H, J(4,3) = 3.5, J(4,5) = 1.7 (H-4 of 2-furoyl)
IIId
IIIe
8.13
8.45
7.58
8.16
1.7
1.7
8.24 d and 7.65 d, 2 H and 2 H, J = 8.9 (4-nitrophenyl);
4.25 q, 2 H, J = 7.1 (OCH2CH3); 1.25 t, 3 H, J = 7.1
(OCH2CH3)
8.25 d and 7.78 d, 2 H and 2 H, J = 8.8 (4-nitrophenyl)
a
Compounds IIIa – IIId in CDCl3, compound IIIe in (CD3)2SO.
TABLE IV
The EI mass spectra of 4-aryl-3-substituted furans IIIa – IIIe
Compounda
m/z, %
IIIa
293 M+• (18), 189 (20), 142 (11), 114 (25), 113 (15), 105 (36), 88 (11), 77 (100),
63 (25), 51 (48)
283 M+• (62), 237 (52), 209 (62), 181 (38), 153 (41), 152 (62), 105 (64), 77 (100),
76 (24), 51 (28)
238 M+• (100), 221 (28), 209 (30), 181 (57), 153 (39), 152 (34), 115 (69), 95 (37),
63 (26), 39 (47)
IIIb
IIIc
261 M+• (100), 233 (37), 216 (63), 170 (58), 142 (28), 114 (42), 113 (32), 77 (32),
63 (39), 51 (26)
233 M+• (100), 203 (33), 169 (13), 157 (15), 131 (33), 113 (26), 103 (30), 77 (33),
63 (30), 51 (15)
IIId
IIIe
a
For each compound 10 most abundant peaks are given.
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•
subsequent eliminations of CO or CO + H from the M+• ion. The most intense fragment
•
ions in the spectrum of compound IIId are (M − OC2H5)+, m/z 216 (63%) and the ion
•
m/z 170 (58%) arising by subsequent loss of the NO2 radical. On the other hand, in the
•
spectrum of compound IIIe the fragment (M − OH)+, m/z 216, is of very low intensity
•
(less than 2%). In this case, the formation of the fragment (M − NO)+, m/z 203 (33%)
is preferred.
EXPERIMENTAL
The melting points were determined on a Kofler block. IR spectra were recorded on an M-80 spec-
trometer, UV spectra (λ in nm, ε in m2 mol−1) on a Specord UV-VIS M-40 instrument (both Zeiss,
1
Jena). H NMR spectra in deuteriochloroform were obtained with a Tesla BS 587 spectrometer using
tetramethylsilane as internal standard. Mass spectra (EI) were measured on an AEI MS 902 S (Man-
chester); direct inlet, ionization energy 70 eV, electron current 100 µA, source temperature 150 °C.
The starting compounds were prepared according to the literature: 4-phenyloxazole10 (I), 1-phenyl-
3-(4-nitrophenyl)-2-propyn-1-one11–13 (IIa), 1-phenyl-3-(5-nitro-2-furyl)-2-propyn-1-one14
(IIb), 3-phenyl-1-(2-furyl)-2-propyn-1-one15 (IIc), and ethyl 3-(4-nitrophenyl)-2-propynoate16 (IId).
General Procedure for Preparation of Compounds IIIa – IIId
A mixture of 4-phenyloxazole (I; 2.0 g, 14 mmol), compound IIa – IId (14 mmol) and hydroquinone
(0.1 g) was heated at 180 – 190 °C for 9 h under continuous stirring by introduction of nitrogen.
After cooling, the crude product was dissolved in a minimum amount of chloroform (IIIa and IIIb),
benzene (IIIc) or chloroform–1,2-dichloroethane (2 : 1) (IIId) and chromatographed on a column of
silica gel in the respective solvent. After removal of the solvent, the product was further purified by
crystallization from ether–light petroleum (IIIa), ethanol (IIIb, IIId) or hexane (IIIc). For yields,
melting points and elemental analyses see Table I.
4-(4-Nitrophenyl)-3-furancarboxylic Acid (IIIe)
Ester IIId (0.4 g, 1.5 mmol) was refluxed with a solution of potassium hydroxide (0.2 g, 3 mmol) in
50% aqueous ethanol (20 ml) for 4 h. The alcohol was evaporated, the residue diluted with the same
amount of water and extracted twice with 1,2-dichloroethane (10 ml). The aqueous solution of the
potassium salt was treated with charcoal, filtered, cooled and acidified with dilute (1 : 1) hydro-
chloric acid. The deposited crude product was crystallized from ethanol. For yields, melting points
and elemental analyses of the obtained acid IIIe see Table I.
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Translated by M. Tichy.
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