Synthesis and reactions of some new benzopyranone derivatives with potential biological activities

Article abstract of DOI:10.1002/jhet.5570450648

(Chemical Equation Presented) Reaction of visnaginone which derived from the naturally occurring compound "visnagine", with ally! bromide gave O-allyl visnaginone 1, which underwent Claisen rearrangement to yield 7-allylbenzofuran 2 derivative. Vilsmeier

Full text of DOI:10.1002/jhet.5570450648

Nov-Dec 2008
1855
Synthesis and Reactions of Some New Benzopyranone Derivatives
With Potential Biological Activities
*El-Sayed I. El-Desoky and Shar S. Al-Shihry
Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt,
E-mail: desoky199@yahoo.com
Received November 29, 2007
O
O
O
OCH3
O
OCH3
OCH3
O
O
OCH3
CN
CH=X
N
Ar
NH2
O
N
O
O
O
OH
10a
X
CH3
O
X
3 - 9
R
18 - 21
X= O, S
16a-e
X=O, NH, CN,
cyclohex., Indandione
Reaction of visnaginone which derived from the naturally occurring compound "visnagine", with allyl
bromide gave O-allyl visnaginone 1, which underwent Claisen rearrangement to yield 7-allylbenzofuran 2
derivative. Vilsmeier Haack formylation of 2 afforded our versatile starting compound furochromene-6-
carboxaldehyde (3) which was condensed with cyclohexane-1,3-dione, indandione, malononitrile or ethyl
cyanoacetate to yield the ylidene nicotinonitrile and pyridone derivatives 4,7,10a-b. Reaction of 3 with
aniline or aniline acting on multiple function X-H (X = NH, O, S) at its ortho position afforded the
corresponding anils, imidazolylfurochromene and azepines compounds 11-17. On the other hand, oxidation
of visnagin afforded chromene-6-carboxaldehyde derivative 18 which was condensed with different aryl or
(heteroaryl) acetonitrile followed by hydrolysis to give pyrano[3,2-g]chromen-4,8-dione derivatives 20a-d
and 22.
J. Heterocyclic Chem., 45, 1855 (2008).
INTRODUCTION
synthesis of antitumor agents brnzopyranone acetic acid
analogues [25-28].
Visnagin is an active principle extracted from the fruits
of Ammi visnaga [1] The fruit or its isolated active
components have been used for the treatment of angina
pectoris due to their peripheral and coronary vasodilator
activity [2] In isolated aorta, visnagin, and other related
active principles present in these fruits such as visnadin
and khellin inhibited vascular smooth muscle contractility
(VSNC) probably by acting or multiple sites to decrease
the availability of Ca2+ required for activation [3-6], lipid
altering activity for example decreasing the atherogenic
cholesterol fraction, elevating antiatherogenic HDL
cholestrol fraction and antiatherosclerotic activity [7-9].
Also, benzopyranones and furobenzopyranones are
compounds of considerable significance as a result of
their wide spread occurrence in plants and their potential
as important pharmaceuticals in the treatment of renal
colic, anginal syndromes, whopping cough, peptic ulcer,
DNA stand breaking activity and mutagenicity, antiviral
agent, antiproliferation agent, antitumor and central
nervous system (CNS) activity, in photochemotherapy
treatment of a variety of skin diseases such as psoriasis,
vitiligo, mycosis fungicides [10-16]. In view of these facts
and in continuation of our research program in this field
[17-24], we present here the synthesis of some benzodi-
pyranone and furobenzopyranones derivatives, the latter
compounds are consider very interesting precursors to
RESULTS AND DISCUSSION
Chromone-3-carboxaldehyde has been extensively used
in the synthesis of various heterocyclic systems. The
synthesis and reactivity of the versatile compound have
been reviewed [29-31]. We present here the synthesis of
new allylfurochromone-3-carboxaldehyde as starting
material in the synthesis of condensed or isolated hetero-
cyclic furobenzopyranones derivatives. O-allylation of 5-
acetyl-6-hydroxy-4-methoxy-benzofuran "visnaginone"
[32] which was previously prepared from hydrolysis of
the naturally occurring compound "visnagin" gave the
corresponding O-allyl visnaginone (1). Compound 1
was refluxed in N,N-diethylaniline and underwent
Claisen rearrangement to provide 5-acetyl-7-allyl-6-
hydroxy-4-methoxybenzofuran (2) in quantitative yield
[24] (Scheme 1).
The versatile starting compound, 9-allyl-4-methoxy-5-
oxo-5H-furo[3,2-g]chromene-6-carbaldehyde (3) was
obtained in good yield from Vilsmeier-Haack formylation
of compound 2. The 1H NMR spectra of the latter product
revealed disappearance the singlet CH3 at 2.45, whereas
two singlets appeared at ꢀ 8.25 and 10.20 ppm.
Condensation of 3 with cyclohexane-1,3-dione or
indandione provides the expected mono adducts 4 and 7

1856
E.-. I. El-Desoky and S. S. Al-Shihry
Vol 45
Scheme 1
OMe
OMe
O
OMe
O
O
Allyl bromide
COCH3
O
KOH
CH3
K2CO3
O
O
O
Me
OH
Visnagin
1
Visnaginone
O
OMe O
Fries
Rearrangement
O
O
O
O
O
7
Piperidine.
O
OMe
O
OMe O
OMe
O
O
COCH3
OH
CHO
POCl3
DMF
O
O
O
O
O
O
Pip.
4
3
2
O
O
O
O
tw
o m
oles
Piperidine.
Piperidine.
one m
ol
e
O
O
O
O
O
O
OMe
OMe
O
- H2O
O
O
O
O
O
O
6
5
respectively. The mono adduct 4 was reacted again with
another molecule of cyclohexane-1,3-dione to yield
the 2:1 adduct 5 which underwent dehydration
simultaneously to form 9-(9-allyl-4-methoxy-5-oxo-5H-
(9) [30b] The infra-red spectrum of 9 showed clearly
disappearance of the imino absorption band at ꢀ = 1620
cm-1 instead, a new band at ꢀ = 2230 cm-1 for CꢁN group
was appeared.
furo[3,2-g]chromen-6-yl)
methylene)-3,4,5,6,7,9-hexa-
Condensation of the chromene-6-carbaldehyde 3 with
malononitrile or ethyl cyanoacetate in the presence of
ammonium acetate afforded 5-(7-allyl-6-hydroxy-4-
methoxybenzofuran-5-carbonyl)-2-aminonicotinonitrile
(10a) and 5-(7-allyl-6-hydroxy-4-methoxybenzofuran-5-
carbonyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (10b)
respectively (Scheme 2). The reaction mechanism
involves an initial formation of the corresponding ylidene
compounds followed by aminolysis of pyrone ring
thereafter, nucleophilic attacking of the amino group to
the cyano or the ester group simultaneously to form the
products 10a,b. Change of the reaction conditions in some
analogue compounds gave different products as outlined
in the literature [33]
hydro-1H-xanthene-1,8-(2H)-dione (6). The same product
6 was prepared directly from reaction of the chromone-3-
carboxaldehyde 3 with two moles of cyclohexane-1,3-
dione [30b,d].
The latter products 4-7 have been characterized by
elemental and spectroscopic analyses, the mass spectrum
of 6 revealed in addition to the molecular ion peak, one
daughter ion peak (M1) at m/z 378 from extrusion
cyclohexenone group and the base peak at m/z 294 due to
extrusion oxirene and cyclopropene groups from the
daughter ion M1.
Compound 3 was condensed with hydroxylamine
hydrochloride in ethanol to give a quantitative yield of the
corresponding hydroxyiminomethyl chromone 8 which
was refluxed in acetic anhydride to give 9-allyl-4-
methoxy-5-oxo-5H-furo[3,2-g]-chromene-6-carbonitrile
The assigned structure of 10a and 10b were confirmed
by spectral and the elemental analysis. The infra-red
spectra revealed in addition to the hydroxyl and amino

Nov-Dec 2008
Synthesis and Reactions of Some New Benzopyranone Derivatives
1857
Scheme 2
R
OMe
O
OMe O
N
OMe
O
CN
O
CN
N
H
O
O
O
OH
N
H
O
OH
N
NH2
10a
11a-c
OMe
O
O
10b
a ; R =
b ; = Cl
c ; NO2
H
R
CN
NH2
NH2
=
O
CH2(CN)COOEt
AcONH4
AcOH
CH2(CN)2
9
Ph
OMe O
N
Ph
AC2O
N
H
O
O
OMe
O
O
O
O
OMe
zil
Ben
CHO
NH2OH
CH=NOH
12
AcONH4
AcOH
O
O
8
3
OMe O
S
H2N
HX
O
N
R
ArNH2
C6H4OMe-4
O
O
OMe O
14
N
OMe
O
O
R
HX
=
CH=NAr
O
O
Thioglycolic ester
Dry toluene
O
16a-e
- H2
OMe O
13a-d
OMe O
N
S
O
O
The Compounds 13a-d
The Compounds 16 and 17
a; X = NH R = H
O
O
COOEt
X
COOEt
a; Ar = C6H5
b; = C6H4-OMe-4
c; = C6H4-Me-4
15
R
17a-e
b;
c;
d;
e;
= NH
= NH
= S
= Cl
= NO2
= H
N
d;
=
O
= O
= H
absorption bands, the characteristic (CꢀN) band at ꢀ =
2227 cm-1 as well as an amidic absorption band
(compound 10b) at ꢀ = 1640 and 1576 cm-1 indicative of
the amide form concerning compound 10b. 1H-NMR
spectra of 10a showed in addition to the allyl and
aromatic protons, the amino and hydroxyl signals at ꢁ
7.84 and 9.06 ppm.
When 3 is refluxed with 1,2-phenylenediamine, 4-
chloro-1,2-phenylene diamine and 4-nitro-1,2-phenylene-
diamine in glacial acetic acid/ammonium acetate, the
corresponding benzoimidazolyl-benzopyranone derivatives
11a-c were obtained (Scheme 2). The 1H-NMR spectra of
11a-c showed beside the allyl and aromatic protons, a
broad NH signal at ꢁ 12.68-13.12 ppm. By the same
manner, when 3 was condensed with benzil under the
same condition, 9-allyl-6-(4,5-diphenyl-1H-imidazol-2-
yl)-4-methoxyfuro[3,2-g]chromen-5-one
obtained in good yield.
(12)
was
The reaction of primary aromatic amines with different
aromatic or heterocyclic aldehydes seemed to be unique
route for the synthesis of several new Schiff bases which
are known to possess diverse biological activities [34-36].
Also, highly promising for further chemical transfor–
mations as well as a precursor for synthesis hetero-
annulated chromones [37-39]. The reaction of furo-
chromen-6-carbaldehyde 3 with different primary (hetero)
aromatic amines (1:1) molar ratio such as aniline,
p-anisidine, p-toluidine and 2-aminooxazole gave the
corresponding anils (13a-d ) as shown in scheme 2. The
structure of compounds 13a-d was confirmed through the
corresponding elemental analyses and spectral data which
were in accordance with the assigned structures (Tables 1

1858
E.-. I. El-Desoky and S. S. Al-Shihry
Vol 45
Table 1
Characterization data of the newly prepared compounds
M. Formula
(M. Weight)
Calcd.
(Found) C
67.60
Elemental analysis
No.
3
M.p. C°
148-150
Colour
Yield %
95
H
N
Pale brown
C16H12O5
(284.26
C22H18O6
(378.37)
C28H24O7
(472.49)
C25H16O6
(412.39)
C16H13NO5
(299.28)
C16H11NO4
(281.28)
C19H15N3O4
(349.34)
C19H14N2O5
(350.32)
C22H16N2O4
(372.37)
C22H15ClN2O4
(406.82)
C22H15N3O6
(417.37)
C30H22N2O4
(474.51)
C22H17NO4
(359.37)
C23H19NO5
(389.4)
C23H19NO4
(373.40)
C19H14N2O5
(350.32)
C24H24O8S
(472.51)
C22H17N3O6
(419.39)
C22H17NO4S
(391.44)
C22H16N2O4
(372.37)
C22H15ClN2O4
(406.82)
C22H15N3O6
(417.37)
C22H15NO4S
(389.42)
C22H15NO5
(373.36)
C20H14FNO4
(351.33)
C20H14ClNO4
(367.78)
C20H14N2O6
(378.34)
C20H13Cl2NO4
(402.23)
C20H13FO5
(352.31)
4.25
(4.20)
4.79
(4.58)
5.12
(5.33)
3.91
(4.09)
4.38
(4.27)
3.94
(3.79)
4.33
(4.52)
4.03
(4.29)
4.33
(4.50)
3.72
(3.48)
3.62
(3.80)
4.67
(4.88)
4.77
(4.92)
4.92
(4.73)
5.13
(5.02)
4.03
(4.21)
5.12
5.30
4.09
(4.30)
4.38
(4.11)
4.33
(4.50)
3.72
(3.90)
3.62
(3.80)
3.88
(3.66)
4.05
(3.87)
4.02
(4.12)
3.84
(4.01)
3.73
(3.44)
3.26
(3.44)
3.72
(3.82)
3.55
(67.43)
69.83
(69.77)
71.18
(71.03)
72.81
(72.66)
64.21
(64.45)
68.32
(68.51)
65.32
(65.63)
65.14
(65.41)
70.96
(70.71)
64.95
(64.79)
63.31
(63.54)
75.94
(75.81)
73.53
(73.73)
70.94
(71.11)
73.98
(74.22)
65.14
(65.31)
61.01
61.34
63.01
(62.87)
67.50
(67.61)
70.96
(71.20)
64.95
(64.69)
63.31
(63.45)
67.85
(67.61)
70.77
(70.91)
68.37
(68.17)
65.31
(65.50)
63.49
(63.61)
59.72
(59.90)
68.18
(68.36)
65.14
4
215 (ch)
260 (ch)
224 (ch)
Dark brown
Dark bown
Pale brown
Pale yellow
87
90
83
75
80
73
84
82
69
70
92
80
85
85
70
65
80
90
90
77
81
70
88
85
90
90
80
85
85
6
7
8
165-166
4.68
(4.50)
4.98
(4.77)
12.03
(12.44)
8.00
(7.88)
7.52
(7.80)
6.89
(6.71)
10.07
(10.27)
5.90
(5.76)
3.90
(4.00)
3.60
(3.44)
3.75
9
193-196
210-213
204-206
207-210
260-263
185-187
183-185
165-167
138-140
140-143
168-170
185-187
270-273
185-188
232-233
175-179
167-170
215-218
170-172
244-247
261-263
280-282
273-275
281-283
>300
Yellowish
brown
Brown
10a
10b
11a
11b
11c
12
Lustrous
yellow
Yellowish
brown
Dark brown
Reddish
brown
Pale yellow
13a
13b
13c
13d
15
Yellow
Dark yellow
Yellow
(3.87)
8.00
(8.27)
Yellow
Yellow
16c
16d
17a
17b
17c
17d
17e
19a
19b
19c
19d
20a
20b
Pale brown
Yellow
10.02
(10.33)
3.58
(3.85)
7.52
(7.81)
6.89
(7.07)
10.07
(10.30)
3.60
(3.40)
3.75
(3.50)
3.99
(4.13)
3.81
(3.99)
7.40
brownish red
Pale brown
Dark red
Dark yellow
Brown
Yellow
Pale yellow
Pale yellow
Pale yellow
Yellow
(7.27)
3.48
(3.22)
Yellow
C20H13ClO5
(368.77)
(65.30)
(3.27)

Nov-Dec 2008
Synthesis and Reactions of Some New Benzopyranone Derivatives
1859
Table 1. (Continued)
M. Formula
(M. Weight)
Calcd.
(Found)
Elemental analysis
H
No.
20c
20d
21
M.p. C°
>300
Colour
Yield %
80
C
N
3.69
Pale yellow
Yellow
C20H13NO7
(379.32)
C20H12Cl2O5
(403.21)
C21H14N2O4S
(390.41)
C21H13NO5S
(391.40)
63.33
(63.09)
59.58
(59.71)
64.60
(64.88)
64.44
3.45
(3.71)
3.00
(3.85)
>300
95
(3.19)
3.61
(3.47)
3.35
244-247
292-294
Pale yellow
Pale yellow
97
7.18
(7.00)
3.58
22
95
(64.70)
(3.62)
(3.70)
Table 2
Spectral data of the newly prepared compounds
No
3
Spectral data
ir (cm-1) ꢀ = 1700 (CHO), 1650 (C=O), 1590 (C=C) .
1H nmr (CDCl3) ꢁ : 3.40 (d, 2H, 2H-1`, J = 4.59 Hz), 4.01 (s, 3H, OCH3), 5.06 (dd, 1H, H-3`, Jgem= 1.88 Hz, Jcis= 10.02 Hz),
5.08 (dd, 1H, H-3`, Jgem= 1.87 Hz, Jtrans= 15.94 Hz), 6.01 (m, 1H, H-2’), 7.01 (d, 1H, H-3, J = 2.39 Hz), 7.79 (d, 1H, H-2, J =
2.39 Hz), 8.25 (s, 1H, H-7) and 10.20 ppm (s, 1H, CHO).
4
6
7
ir (cm-1) ꢀ = 1705, (C=O), 1684 (C=O, Chromone), 1605 (C=C).
1H nmr (DMSO-d6) ꢁ : 1.7 (m, 2H, H-4 cyclohex.), 3.54 (m, 4H, H-3 and H-5 cyclohex. ), 3.78 (d, 2H, 2H-1`, J = 4.61 Hz),
4.06 (s, 3H, OCH3), 5.03 (m, 2H, 2H-3`), 6.01(m, 1H, H-2), 7.15 (m, 2H, furan H-3 and H-7), 7.82 (d,1H, H-2 furan, J = 2.41
Hz) and 8.08 ppm ( s, 1H, CH=C).
1H nmr (CDCl3) ꢁ : 1.52-2.01 (m, 8H, H-3,4.6,7 xanthene.), 3.18 (m, 4H, H-H-2,8 xanthene.), 3.42-3.56 (m, 3H, 2H-1', H-10
xanthene), 4.04 (s, 3H, OCH3), 5.09 (dd, 1H, H-3`, Jgem= 1.83 Hz, Jcis= 10.15 Hz), 5.18 (dd, 1H, H-3`, Jgem= 1.83 Hz, Jtrans
16.09 Hz), 6.00 (m, 1H, H-2’), 7.56-7.77 (m, 2H, H-2 furan, H-7), 7.85 (d, 1H, H-2, J = 2.46 Hz).
ms m/z (%) 473 (M+1)+ (23), 472 (M+)(30), 378 [M1(M-cyclohexenone)+](14), 294 [M2 (M1- oxirene &cyclopropene)](100).
ir (cm-1) ꢀ = 1710, (C=O), 1678 (C=O, Chromone), 1597 (C=C), 1594, (Ar.),
=
1H nmr (DMSO-d6) ꢁ : 3.85 (d, 2H, 2H-1`, J = 4.55 Hz), 4.13 (s, 3H, OCH3), 5.09 (m, 2H, 2H-3`), 5.91 (m, 1H, H-2), 7.28 (m,
2H, furan H-3 and H-7), 7.56-7.82 (m, 5H, Ar-H and H-2 furan, J = 2.36 Hz) and 8.75 ppm (s, 1H, CH=C).
ms m/z (%) 414 (M+2)+(33), 413 (M+1)+(84), 412 (M)+(10), 411(M-1)+(6).
8
9
ir (cm-1) ꢀ = 3350-3220 (br., OH ), 1655 (C=O), 1620 (C=N) and 1590 (C=C).
1H nmr (CDCl3) ꢁ : 3.52 (d, 2H, 2H-1`, J = 5.71 Hz), 4.11 (s, 3H, OCH3), 5.77 (m, 2H, H-3`), 6.18 (m, 1H, H-2’), 7.01 (d, 1H,
H-3, J = 2.37 Hz), 7.86 (m, 1H, H-2, J = 2.38 Hz), 8.01 (s, 2H, H-7 and CH=N).and 12.70 ppm (s, br. OH).
ir (cm-1) ꢀ = 2230 (CN), 1659 (C=O), 1605 (C=C).
1H nmr (CDCl3) ꢁ : 3.44 (d, 2H, 2H-1`, J = 5.46 Hz), 4.11 (s, 3H, OCH3), 5.06-5.08 (m, 2H, H-3`), 6.05 (m, 1H, H-2’), 7.01
(d, 1H, H-3, J= 2.31 Hz), 7.79 (d, 1H, H-2, J = 2.31 Hz) and 8.10 ppm (s, 1H, H-7).
10a
ir (cm-1) ꢀ = 3385,3331 (Sym. NH2 ) 3485 (OH ), 2221 (CN) , 1676 (C=O), 1619 (C=C), 1586 (Ar.).
1H nmr (DMSO-d6) ꢁ : 3.57 (d, 2H, 2H-1`, J = 5.86 Hz), 3.90 (s, 3H, OCH3), 4.96 (dd, 1H, H-3`, Jgem= 1.72 Hz, Jcis= 10.32
Hz), 5.03 (dd, 1H, H-3`, Jgem= 1.73 Hz, Jtrans= 16.81 Hz),6.02 (m, 1H, H-2’), 7.16 (d, 1H, H-3 furan, J = 2.24 Hz), 7.84 (s, br.,
2H, NH2) , 7.88 (d, 1H, H-2, furan, J = 2.28 Hz), 8.12 (s, 1H, H-6 pyridine) , 8.45 (s, 1H, H-4 pyridine) and 9.06 ppm (s,
br,1H, OH).
10b
ir (cm-1) ꢀ = 3445(strong ,OH ), 3030 (strong, NH ), 2223 (CN), 1689 (C=O) 1620 (C=O , amide), 1610 (C=C)
1H nmr (DMSO-d6) ꢁ : 3.58 (d, 2H, 2H-1`, J = 4.55 Hz), 3.98 (s, 3H, OCH3) , 4.94 (dd, 1H, H-3` Jgem= 1.80 Hz, Jcis= 10.22
Hz) , 4.99 (dd, 1H, H-3, Jgem= 1.80 Hz, Jtrans= 16.86 Hz), 6.00- (m, 1H, H-2’), 7.14 (d, 1H, H-3 furan, J= 2,40 Hz), 7.66 - 7.88
(m, 2H, H-2, furan, H-6 pyridine), 8.45 (s, 1H, H-4, pyridine), 11.60 (s, br., NH ) and 13.20 ppm (s, br, OH).
ir (cm-1) ꢀ = 3375( NH), 1640 (C=O ), 1612-1605 (C=N and C=C ).
11a
11b
1H nmr (DMSO-d6) ꢁ 3.61 (d, 2H, 2H-1`), 4.08 (s, 3H, OCH3), 5.02 (dd, 1H, H-3`), 5.11 (dd, 1H, H-3`), 5.97-6.11 (m, 1H, H-
2’), 7.24 (d, 1H, H-3 furan), 7.88 - 9.12 (m, 6H, Ar.H) and 12.68 ppm (d, 1H, NH).
ir (cm-1) ꢀ = 3390 (NH), 1650 (C=O), 1610-1590 (C=N and C=C ).
1H nmr (DMSO-d6) ꢁ : 3.63 (d, 2H, 2H-1`, J = 4.30 Hz), 4.09 (s, 3H, OCH3), 5.01 (dd, 1H, H-3`, Jgem= 1.83 Hz, Jcis= 10.11
Hz), 5.08 (dd, 1H, H-3`, Jgem= 1.82 Hz, Jtrans= 16.77 Hz), 6.00 (m, 1H, H-2’), 7.37 (d, 1H, H-3 furan, J = 2.37 Hz), 7.88-9.13
(m, 5H, Ar.H) and 12.56 ppm (s, 1H, NH).
ms m/z (%) 408 (M+2)+(32), 406(M)+ (39), 377 (M-C2H6)+(100).
11c
12
ir (Cm-1) ꢀ = 3390( NH), 1655 ( C=O ), 1620-1600 ( C=N and C=C ), 1560, 1395 (NO2).
1H nmr (DMSO-d6) ꢁ : 3.71 (d, 2H, 2H-1`, J = 4.33 Hz), 4.13 (s, 3H, OCH3), 5.02 (dd, 1H, H-3`, Jgem= 1.73 Hz, Jcis= 10.23
Hz), 5.08 (dd, 1H, H-3`, Jgem= 1.73 Hz, Jtrans= 16.62 Hz), 5.90-6.10 (m, 1H, H-2’), 7.37 (d, 1H, H-3 furan, J = 2.23 Hz), 7.88-
9.13 (m, 5H, Ar.H) and 13.12 ppm (d, 1H, NH).
ms m/z (%) 419 (M+2)+ (28), 418(M+1)+(87), 417 (M)+(100), 371(M-NO2)+ (40)
ir (cm-1) ꢀ = 3390 (NH), 1655 ( C=O ), 1625-1615 (C=N and C=C).
1H nmr (DMSO-d6) ꢁ : 3.81 (d, 2H, 2H-1`, J = 5.01 Hz), 4.03 (s, 3H, OCH3), 5.13 (dd, 1H, H-3`, Jgem= 1.78 Hz, Jcis= 11.01
Hz), 5.21 (dd, 1H, H-3`, Jgem= 1.75 Hz, Jtrans= 15.81 Hz), 6.09 (m, 1H, H-2’), 7.37 (d, 1H, H-3 furan, J = 2.37 Hz), 7.45-
8.88 (m, 12H, Ar.H) and 10.10 ppm (s, 1H, NH).
ms m/z (%) 476 (M+2)+(43), 475 (M+1)+(100), 474 (M)+(88).

1860
E.-. I. El-Desoky and S. S. Al-Shihry
Vol 45
Table 2 (Continued)
No
Spectral data
13a
ir (cm-1) ꢀ = 1650 (C=O ) , 1615-1590 (C=N and C=C).
1H nmr (CDCl3) ꢁ : 3.66 (d, 2H, 2H-1`, J = 4.49 Hz), 3.90 (s, 3H, OCH3), 4.96-5.08 (m, 2H, H-3`), 6.09-6.20 (m, 1H, H-2’)
and 6.92 -7.60 ppm (m, 8H, Ar-H, CH=N).
ir (cm-1) ꢀ = 1648 ( C=O ) , 1612-1600 ( C=N and C=C ).
13b
13c
1H nmr (CDCl3) ꢁ : 3.64 (d, 2H, 2H-1`, J = 4.53 Hz), 3.85 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 4.96-5.08 (m, 2H, H-3`), 6.00-
6.20 (m, 1H, H-2’) and 6.88-7.51ppm (m, 7H, Ar-H, CH=N) .ms m/z (%)390 (M+1)+ (6), 389 (M)+(11), 282 (M-
C7H7O)+(28).
ir (cm-1) ꢀ = 1653 (C=O ), 1618-1605 (C=N and C=C).
1H nmr (CDCl3) ꢁ : 2.34 (s, 3H, CH3) , 3.71 (d, 2H, 2H-1`, J = 4.49 Hz), 4.18 (s, 3H, OCH3) , 4.98-5.08 (m, 2H, H-3`), 6.00-
6.20 (m, 1H, H-2’) and 6.80-7.54 ppm (m, 7H, Ar-H, CH=N).
ms m/z (%) 374 (M+1) (2), 373 (M+) (4).
13d
15
1H nmr (DMSO-d6) ꢁ : 3.38(d, 2H, 2H-1`), 4.03 (s, 3H, OCH3) , 4.96-5.08 (m, 2H, H-3`) , 5.90-6.10 (m, 1H, H-2’) , 6,82 (s,
1H, H-7), 7.11 (d, 1H, H-3, J = 2.36 Hz), 7.90-8.40 (m, 2H, Ar-H) , 8.49 (s, 1H , CH=N) and 8.77ppm (s, 1H, H-7).
ms m/z (%) 351 (M+1)+(26), 350 (M+) (42), 349 (M-H)+ (29), and 282 (M- Oxazole ring)+ (100).
IR(Cm-1) ꢀ = 1646 (br., C=O), 1614 (C=C).
1H nmr (CDCl3) ꢁ : 1.97 (t. 6H, CH3CH2 , two groups), 3.60-3.78 (m, 4H, 2H-1`, =CH2-S-CH), 3.98-4.14 (m, 9H. OMe & –
S-CH-CH-, & CH3CH2 two groups), 5.03 (m, 2H, H-3`), 6.00 (m, 1H, H-2’), 6.97 (d, 1H, H-3, J = 2.48 Hz), and 7.59 ppm
(d, 1H, H-2, J = 2.45 Hz)
16c
16d
ir (cm-1) ꢀ = 3255 (br., NH2), 1648 (C=O ), 1605 (C=N, C=C), 1523,1343 (NO2)
1H nmr (CDCl3) ꢁ : 3.75 (d, 2H, 2H-1`, J = 6.0 Hz), 4.01 (s, 3H, OCH3), 5.03 (dd, 1H, H-3`, Jgem= 1.73 Hz, Jcis= 10.23 Hz),
5.09 (dd, 1H, H-3`, Jgem= 1.73 Hz, Jtrans= 16.62 Hz), 6.00-6.09 (m, 1H, H-2’), 7.32 (d, 1H, H-3 furan, J = 2.3 Hz), 7.75-8.40
(m, 5H, Ar.H and H-2 furan), 9.23 (s, br, 1H, CH=N) and 13.20 ppm (s, br., 2H, NH2).
ir (cm-1) ꢀ = 3446 ( br., SH), 1646 (C=O ), 1613 (C=N ), 1605 (C=C).
1H nmr (CDCl3) ꢁ : 3.69 (d, 2H, 2H-1`, J = 6.0 Hz), 3.91 (s, 3H, OCH3), 5.12 (dd, 1H, H-3`, Jgem= 1.87 Hz, Jcis= 10.71 Hz),
5.18 (dd, 1H, H-3`, Jgem= 1.86 Hz, Jtrans= 16.59 Hz), 6.11 (m, 1H, H-2’), 7.27 (d, 1H, H-3 furan, J = 2.6 Hz), 7.41-7.90 (m,
6H, Ar.H , 6H), 8.52 (s, br, 1H, CH=N) and 10.11 ppm (s, br., 1H, SH).
ms m/z (%) 391 (M)+ (7), 390 (M-H)+(13), 360 (M-Sulfur atom)+(27), 124 (100).
ir (cm-1) ꢀ = 1650 ( C=O ) , 1590 (br., C=N and C=C).
17a
17b
1H nmr (CDCl3) ꢁ : 3.61 (d, 2H, 2H-1`, J = 4.46 Hz), 3.98 (s, 3H, OCH3), 4.95 (dd, 1H, 1H-3`, Jgem= 1.56 Hz, Jcis= 10.04 Hz),
5.03 (dd, 1H, H-3`, Jgem= 1.58 Hz, Jtrans= 17.12 Hz) 6.00 (m, 1H, H-2’), 7.11-7.29 (m, 3H , H-3 and Ar-H), 7.88 (d, 1H , H-2,
J = 2.7 Hz), 8.53 (d, 2H, Ar.H), 9.05 (s, br., 1H, N=CH) and 14.15 ppm (s, 1H, NH).
ms m/z (%) 374 (M+2)+(39), 373 (M+1)+(66), 372 (M)+(100), 371 (M-H)+(48), 217 (49).
1H nmr (DMSO-d6) ꢁ : 3.58 (d, 2H, 2H-1`, J = 4.53 Hz), 3.95 (s, 3H, OCH3), 4.96 (dd, 1H, H-3`, Jgem= 1.66 Hz, Jcis= 10.04
Hz) , 5.01 (dd, 1H, H-3`, Jgem= 1.67 Hz, Jtrans= 16.80 Hz) ,5.99 (m, 1H, H-2’), 7.13 (d, 1H, H-3 furan, J = 2.35 Hz), 7.25-7.28
(m, 2H, Ar.H, H-8,11 ), 7.87 (d, 1H,H-2 furan, J = 2.35 Hz), 8.47 (d, 1H, Ar.H , H-10, J = 4.12 Hz), 9.48 (s, br, 1H, CH=N)
and 14.09 ppm (s, 1H, NH).
17c
17d
17e
19a
19b
ir (cm-1) ꢀ = 3338 (NH), 1650 (C=O ), 1612 (C=N ), 1521,1331 (NO2).
1H nmr (DMSO-d6) ꢁ : 3.79 (d, 2H, 2H-1`, J = 4.71 Hz), 4.05 (s, 3H, OCH3), 4.85-5.05(m, 2H, H-3'), 6.00-6.09 (m, 1H, H-
2'), 7.34-8.46 (m, 5H, Ar.H) and 9.27 ppm (s, br, 1H, CH=N), 12.8 (s, br. NH)
1H nmr (CDCl3) ꢁ : 3.87 (d, 2H, 2H-1`), 4.27 (s, 3H, OCH3), 5.11 (dd, 1H, H-3`), 5.16 (dd, 1H, H-3`), 6.02-6.18 (m, 1H, H-
2’), 7.12 (d ,1H, H-3 furan), 7.20-7.40 (m, 2H, Ar.H), 7.69 (d, 1H, H-2 furan), 8.00-8.10 (m, 2H, Ar.H ) and 9.23 ppm (s, 1H,
CH=N).
1H nmr (CDCl3) ꢁ : 3.89 (d, 2H, 2H-1`), 4.18 (s, 3H, OCH3), 5.15 (dd, 1H, H-3`), 5.19 (dd, 1H, H-3`), 6.01-6.18 (m, 1H, H-
2’), 7.14 (d, 1H, H-3 furan), 7.20-7.40 (m, 2H, Ar.H), 7.69 (d, 1H, H-2 furan), 8.00-8.10 (m, 2H, Ar.H) and 9.01ppm (s, 1H,
CH=N).
ir (cm-1) ꢀ = 3425 (NH), 1654 (C=O), 1601 (Ar).
1H nmr (DMSO-d6) ꢁ : 2.32(s, 3H, CH3), 3.81 (s, br., NH), 4.0 (s, 3H, OMe), 6.21 (s, 1H, H-10), 7.36 (s, 1H, H-3), 7.32 (m,
2H, H-3’,5’), 7.80 (m, 2H, H-2’,6’), and 8.21 ppm (s, 1H, H-6).
ir (cm-1) ꢀ = 3449 (NH), 1670 (C=O ), 1604 (Ar.).
1H nmr (DMSO-d6) ꢁ : 2.38 (s , 3H, CH3), 3.15 (s, br., NH), 3.98 (s, 3H, OMe), 6.17 (s, 1H, H-10), 7.39 (s, 1H, H-3), 7.52
(d, 2H, H-3’,5’, J = 8.6 Hz), 7.80 (d, 2H, H-2’,6’, J = 8.6 Hz), and 8.21 ppm (s, 1H, H-6).
ms m/z (%) 369 (M+2)+(37), 368 (M+1)+(50), 367 (M)+(90), 366 (M-1)+(35)
ir (cm-1) ꢀ = 1655 (C=O), 1593 (C=N), 1508 and 1338 (NO2).
19c
1H nmr (DMSO-d6) ꢁ : 2.35(s, 3H, CH3), 3.77 (s, br., NH), 3.91 (s, 3H, OMe), 6.16 (s, 1H, H-10), 6.77 (s, 1H, H-3), 8.03 (d,
2H, H-2’,6’, J = 6.7 Hz), 8.36 (d, 2H, H-3’,5’, J = 6.7 Hz) and 9.03 ppm (s, 1H, H-6).
ms m/z (%) 379 (M+1)+(31), 378 (M)+ (100), 217 (49).
19d
20a
1H nmr (DMSO-d6) ꢁ : 2.35 (s , 3H, CH3), 3.81 (s, br. NH), 3.98 (s, 3H, OMe), 6.12 (s, 1H, H-10), 7.10 (s, 1H, H-3), 7.10 (s,
1H, H-6), 7.40-7.75 (m, 3H, Ar-H), and 8.77 ppm (s, 1H, H-6).
ir (cm-1) ꢀ = 1739 (-O-C=O), 1654 (C=O), 1607 (Ar).
1H nmr (CDCl3) ꢁ : 2.66 (s , 3H, CH3), 4.11 (s, 3H, OMe), 6.12 (s, 1H, H-10), 6.80 (s, 1H, H-3), 7.41 (m, 2H, H-3’,5’), 7.46
(m, 2H, H-2’,6’), and 8.25 ppm (s, 1H, H-6).

Nov-Dec 2008
Synthesis and Reactions of Some New Benzopyranone Derivatives
1861
Table 2 (Continued)
No
Spectral data
20b
ir (cm-1) ꢀ = 1735 (-O-C=O), 1674 (C=O), 1608 (Ar).
1H nmr (CDCl3) ꢁ : 2.35 (s , 3H, CH3), 3.99 (s, 3H, OMe), 6.12 (s, 1H, H-10), 6.92 (s, 1H, H-3), 7.41-7.46 (m, 4H, Ar-H),
and 8.16 ppm (s, 1H, H-6).
ms m/z (%) 370 (M+2)(29)), 369 (M+1)+ (26), 368 (M)+ (86).
20c
20d
ir (cm-1) ꢀ = 1750 (-O-C=O), 1674 (C=O), 1600 (C=C) 1510 and 1345 (NO2).
1H nmr (DMSO-d6) ꢁ : 2.49 (s , 3H, CH3), 4.03 (s, 3H, OMe), 6.31 (s, 1H, H-10), 7.05 (s, 1H, H-3), 7.50-8.03 (m, 4H, Ar-
H), and 8.44 ppm (s, 1H, H-6).
ms m/z (%) 381 (M+2)+ (8) ), 380 (M+1)+ , 379 (M)+ (100), and 322 ( M- HNO2) (55).
ir (cm-1) ꢀ = 1742 (-O-C=O), 1660 (C=O), 1600 (C=C).
1H nmr (DMSO-d6) ꢁ : 2.33 (s, 3H, CH3), 3.94 (s, 3H, OMe), 6.19 (s, 1H, H-10), 7.28 (s, 1H, H-3), 7.10 (s, 1H, H-6), 7.40-
8.60 (m, 3H, Ar-H). and 8.34 ppm (s, 1H, H-6).
ms m/z (%) 406 (M+4)+(13), 405 (M+3)+(22), 404 (M+2)+(72), 403 (M+1)+(35), 402 (M)+ (100), 345 (60)
ir (cm-1) ꢀ = 3350 (NH), 1660 (C=O), 1609 (C=N), 1600 (Ar.).
21
22
1H nmr (CDCl3) ꢁ : 2.35(s , 3H, CH3), 4.11 (s, 3H, OMe), 6.07 (s, 1H, H-10), 7.00 (s, 1H, H-3), 8.12-8.44 ( m , 4H, Ar.H )
and 8.58 ppm (s, 1H , H-6).
ir (cm-1) ꢀ = 1725 (-O-C=O), 1655 (C=O ), 1609 (C=N), 1600 (Ar.).
1H nmr (CDCl3) ꢁ : 2.37 (s, 3H, CH3), 4.18 (s, 3H, OMe), 6.10 (s, 1H, H-10), 7.15 (s, 1H, H-3), 8.16-8.42 (m, 4H, Ar.H) and
9.39 ppm, (s, 1H , H-6).
ms m/z (%) 414 (M)+ (90).
and 2). The base peak ion of the compounds 13a-d have
an m/z value (282) of the corresponding [C16H12NO4]
showing that the most favoured point of rupture occurs
between the ring residue of the aromatic amine and the
imino group.
Heating of 13b with ethyl glycolate under reflux in dry
toluene, the product 15 could be isolated and not the
expected thiazolidinone derivative 14 [40]. All the
instrumental analyses which were performed on
compound 15 confirmed the suggested structure, the mass
spectrum gave the molecular ion M+ at m/z = 472 which is
in complete with its molecular weight [C24H24O8S], in
addition to the base peak at m/z = 294 from extrusion of
sulfur atom and two COOEt groups. The suggested
mechanism of the formation the compound 15 is shown in
Scheme 3.
[39], thus, condensation of a suitable reactant at two of
these sites afforded new ring system. Reaction of 3 with
aniline having a nucleophilic function X-H (X = NH, O,
S) at ortho position such as 1,2-phenylenediamine, 4-
chloro-1,2-phenylenediamine, 4-nitro-1,2-phenylene-
diamine, 2-aminothiophenol and 2-aminophenol afforded
first the corresponding anils 16a-e. The latter Schiff bases
underwent nucleophilic addition of the X-H on the C-2,
followed by dehydrogenation by air to form the cyclized
azepine derivatives 17a-e (Scheme 2). The latter
compound 16a-e and 17a-e were established from their
elemental analyses as well as spectral data which are in
accordance with the assigned structures (Tables 1 and 2).
The interesting bioactivities of the naturally-occurring
benzodipyranones as antibacterial, tuberculostatic and
molluscicidal agents [41] promoted us to undertake a
synthetic study of this nucleus to study their biological
activities. Compound 7-hydroxy-5-methoxy-2-methyl-4-
6-Formylfurochromen-5-one contains three potential
sites of nucleophilic attack C-7, C-5 and 6-formyl group
Scheme 3
HS
COOEt
NAr
S
COOEt
OMe
O
O
OMe
O
O
OMe
O
S
COOEt
NHAr
COOEt
COOEt
O
O
O
O
H
ArNH2
SH
13b
Ar = C6H4OMe-4
HS
OMe
O
O
OMe
O
O
H2S
S
S
O
O
COOEt
COOEt
COOEt
COOEt
HS
15

1862
E.-. I. El-Desoky and S. S. Al-Shihry
Vol 45
recorded (KBr discs) on
a
Shimadzu FT-IR 8201 PC
oxo-4H-chromene-6-carbaldehyde (18) was prepared
from oxidation of the naturally occurring visnagin as
outlined in the literature [42].
1
spectrophotometer. H NMR spectra were carried out in CDCl3
and (CD3)2SO solutions on a Varian Mercurry V-300 MHz
spectrometer and chemical shifts were expressed in ꢀ units using
TMS as internal reference, Mass spectra were recorded on a GC-
MS-QP-1000EX mass spectrometer at 70 e.V.(Faculty of
Science, Cairo university). Elemental analyses were carried out
in the CHN Elementar Autoanalyzer unit, Faculty of Science,
King Faisal University. Thin layer Chromatography Silica gel 60
F254. Layer thickness 0.2 mm. Tables 1 and 2 show the
characterization and spectral data of the newly prepared
compounds.
The compounds visnaginone, 5-Acetyl-6-allyloxy-4-methoxy-
benzofuran (1), 5-Acetyl-7-allyl-6-hydroxy-4-methoxybenzo-
furan (2) and 7-hydroxy-5-methoxy-2-methyl-4-oxo-4H-
chromene-6-carbaldehyde (18) were prepared by the same
procedures as outlined in the published literatures [24,32,42].
9-Allyl-4-methoxy-5-oxo-5H-furo[3,2-g]chromene-6-car-
boxaldehyde (3). To a stirred solution of compound 2 (2.46 g,
10 mmol) in dimethylformamide (30 ml), phosphorous
oxychloride (15 ml) was added drop wise at 0-5°C during about
10 min. The mixture was stirred at room temperature for 5 hrs,
and hydrolysed by ice-water. The resulting precipitate was
collected by filtration, washed with water and crystallized from
ethanol to yield 3 as pale brown powder.
When an equimolar mixture of 18 and a number of
phenylacetonitrile derivatives such as 4-fluoro-, 4-chloro-
,4-nito- and 2,4-dichloro phenylacetonitrile was refluxed
in ethanol and in a presence of a few drops of piperidine,
the corresponding 7-aryl-8-imino pyrano[3,2-g]chromen-
4(8H)-one derivatives 19a-d were obtained quantitatively.
The corresponding 7-aryl pyrano [3,2-g] chromen-4,8-
dione derivatives 20a-d were obtained by hydrolysis of
19a-d in acetic acid (Scheme 4).
By the same manner, when 18 was condensed with
benzothiazole-2-acetonitrile, 7-(benzo[d]thiazol-yl)-8-
imino-5-methoxy-2-methylpyrano[3,2-g]chromen-4(8H)-
one (21) was formed. Hydrolysis of 21 by using acetic
acid, the corresponding pyranochromendione 22 was
obtained. The corresponding open ylidene compounds not
obtained as reported in the literature [43]. The infra-red
spectra of the products 19a-d and 21 showed absence of
(CꢀN) absorption peak, that is confirm the outlined
suggested reaction pathway (Scheme 4)
Condensation of compound 3 with cyclohexane-1,3-dione
and indanedione. Synthesis of the compounds 4 and 7. To a
solution of the aldehyde 3 (1.42 g, 5 mmol), and the appropriated
active methylene compound (5 mmol) in absolute ethanol (20
mL), piperidine (0.5 mL) was added. The reaction mixture was
EXPERIMENTAL
All melting points were determined on an electrothermal
Gallenkamp apparatus and are uncorrected. IR spectra were
Scheme 4
N
OCH3 O
CH3COOH
S
O
O
O
CH3
22
N
OCH3 O
N
S
CN
S
HN
O
O
CH3
21
Piperidine
OCH3
O
O
OHC
HO
R1
CN
CH3
R2
R2
R1
18
OCH3
O
Piperidine
HN
O
O
CH3
R2
R1
19a-d
OCH3 O
CH3COOH
Compounds 19 and 20
a ; R1 = H R2 = F
O
O
O
CH3
20a-d
b ;
c ;
d;
= H
= H
= Cl
= Cl
= NO2
= Cl

Nov-Dec 2008
Synthesis and Reactions of Some New Benzopyranone Derivatives
1863
refluxed for 3 hrs. The solid that was obtained was collected by
filtration, washed with ethanol, dried and crystallized from ethanol
to give the corresponding 1:1 adducts 4 and 7.
20 hrs the reaction mixture was left overnight at room
temperature. The precipitate that was formed was collected by
filtration, dried well and crystallized from ethanol to give the
compound 15.
9-(9-Allyl-4-methoxy-5-oxo-5H-furo[3,2-g]chromen-6-yl)-
methylene)-3,4,5,6,7,9-hexahydro-1H-Xanthene-1,8-(2H)-
dione (6) Method A. To a solution of the mono adduct 4 (0.38
g, 1 mmol), and cyclohexane-1,3-dione (1.1 mmol) in absolute
ethanol (20 mL), piperidine (0.2 mL) was added. The reaction
mixture was refluxed for 3 hrs. The solid that was obtained was
collected by filtration, washed with ethanol, dried and
crystallized from ethanol to give compound 6 directly without
separation of the diadduct 5 (Table 1 and 2).
Method B. Compound 6 was also prepared directly upon
treatment of compound 3 with cyclohexane-1,3-dione (1:2
moles), according to the procedure previously described for the
synthesis of compound 4 (Tables 1 and 2).
9-Allyl-4-methoxy-5-oxo-5H-furo[3,2-g]chromene-6-car-
baldehyde oxime (8). To a well-stirred solution of compound 3
(2.84 g, 10 mmol) in ethanol (30 mL), hydroxylamine
hydrochloride (0.77 g, 11 mmol) was added. The solution was
stirred vigorously for 5 hrs, and the reaction mixture was left
overnight at room temperature. The solid that was obtained was
collected by filtration, washed with water, dried and crystallized
from ethanol to give compound 8 as pale yellow crystals.
9-Allyl-4-methoxy-5-oxo-5H-furo[3,2-g]chromene-6-carbo-
nitrile (9). A solution of compound 8 (1.50 g, 5 mmol) in acetic
anhydride (10 mL) was heated at 100°C for 2 hrs. The
precipitate that formed after cooling, was collected by filtration,
washed with water, dried and crystallized from ethanol to give
compound 9 as yellowish brown crystals.
Condensation of 18 with aryl and heteroaryl aceto-
nitriles; synthesis of the compounds 19a-d and 21. General
procedure. Equimolar amounts of the aldehyde 18 [42] (1.17 g,
5 mmol), the appropriated acetonitriles (5 mmol) and few drops
of piperidine in absolute ethanol (20 mL) were refluxed for 5
hrs. The solid that separated during refluxing was collected by
filtration, dissolved with hot ethanol, dried and crystallized from
ethanol to give the corresponding 7-aryl (and heteroaryl)-8-
imino pyrano[3,2-g]chromen-4(8H)-one derivatives 19a-d and
21. The products 19a-d and 21 are sufficiently pure for using in
the following step.
Synthesis of pyrano[3,2-g]chromen-4,8-dione derivatives
20a-d and 22. General procedure. The appropriate pyrano[3,2-
g]chromen-2-imine-6-one 19a-d or 21 (1 g) in glacial acetic acid
(20 mL) was boiled for 1 h. After allowing it to cool to room
temperature, fine crystals were formed that were collected by
filtration, washed with hot ethanol, dried and then crystallized
from acetone to give the corresponding pyrano[3,2-g]chromen-
4,8-diones 20a-d and 22 (Tables 1 and 2).
Acknowledgements.
The financial support by the
deanship of scientific research at King Faisal University is
gratefully acknowledged.
REFERENCES
5-(7-Allyl-6-hydroxy-4-methoxybenzofuran-5-carbonyl)-2-
aminonicotinonitrile (10a) and 5-(7-allyl-6-hydroxy-4-
methoxybenzofuran-5-carbonyl)-2-oxo-1,2-dihydropyridine-
3-carbonitrile (10b). A mixture of compound 3 (2.84 g, 10
mmol), malononitrile or ethyl cyanoacetate (10 mmol) and
ammonium acetate (4 g) was refluxed in glacial acetic acid (25
mL) for 4 hrs. After cooling, the reaction mixture was poured on
crushed ice and the solid that separated was collected by
filtration, dried and crystallized from ethanol to give 10a as
brown crystals or 10b as lustrous yellow solid.
Synthesis of imidazolyl furochromen-5-one derivatives
11a-c and 12. General procedure. A mixture of compound 3
(1.42 g, 5 mmol), ammonium acetate (2 g) and 1,2-phenyl-
enediamine or 4-chloro-1,2-phenylenediamine or 4-nitro-1,2-
phenylenediamine or benzil (5 mmol) as appropriate was
refluxed in glacial acetic acid (15 mL) for 3 hrs, the reaction
mixture was poured on crushed ice, the precipitate that was
formed was collected by filtration, washed with water, dried and
crystallized from ethanol to give the corresponding imidazolyl
furochromen-5-one (Tables 1 and 2).
Condensation of 3 with aromatic amines; synthesis of
Schiff bases 13a-d, 16a-e and 17a-e. General procedure.
Equimolar amounts of the aldehyde 3 (1.42 g, 5 mmol), and the
appropriated amine (5 mmol) in absolute ethanol (20 mL) were
refluxed for 2-5 hrs (TLC control). The precipitated solid was
collected by filtration, washed with hot ethanol, dried and
crystallized from ethanol to give the corresponding anils 13a-d
and 16a-e. Further reflux of the compounds 16a-e under the
same conditions afforded the corresponding azepines 17a-e.
Reaction of 13b with ethyl thioglycolate; synthesis of the
compound (15). A mixture of 13b (2 g, 5 mmol) and ethyl
thioglycolate (1.2 g, 10 mmol) in dry toluene was refluxed for
*
Present address: Department of Chemistry, College of
Science, King Faisal University, Hofuf 31982 Eastern Province, Saudi
Arabia
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