Reactions of some anellated 2-aminothiophenes with electron poor acetylenes

Article abstract of DOI:10.1016/j.tet.2006.04.037

The reactivity of 2-aminothiophenes in two different anellations: (a) [b]-anellation to a saturated carbocycle and (b) [3,4-c]-anellation to benzopyrans, towards typical acetylenic dienophiles has been investigated. Because of the absence of conjugation, the thiophenes of type (a) do not undergo [4+2]-cycloaddition with acetylenic dienophiles. Instead, the N-vinylated products 2 and 3 were obtained with dimethyl acetylene dicarboxylate (DMAD). Electron poor alkynes react with the thiophenes of type (b) in three main ways: DMAD reacts in a [4+2]-mode in dioxane to give the products 7, 8 and 14; a Michael addition type reaction also takes place at the doubly vinylene homologous carbon atoms (C-1 in the starting materials 4, 9 and 10) in dioxane, methanol or ethanol. Methyl propiolate reacts in a similar way. The doubly N-vinylated product 26 was obtained from 10 in toluene and the C-1 vinylated products 24B and 27 were obtained from 9 in dioxane and 10 in methanol. The reaction of 10 with phenyl ethyl propiolate in dimethylformamide gave no addition product, instead a dimer of the acetylenic reagent was the isolated product. The accuracy of the assigned structures 5, 12 and 13a could be achieved on the basis of a single-crystal X-ray structure analysis of compound 13a. The reaction mechanism and the nature of the isolated products are dependent on the nature of the solvent. No addition reaction was observed between 17 and DMAD. The influence of the N-substitution on the nature of the addition (Michael or Diels-Alder) could be settled through the reactions of 18 and 21 with DMAD, which gave 19 and 14 (via 22), respectively as the only isolable products.

Full text of DOI:10.1016/j.tet.2006.04.037

Tetrahedron 62 (2006) 7121–7131
Reactions of some anellated 2-aminothiophenes with
electron poor acetylenes
a,
Emmanuel Sopbue Fondjo, Dietrich Dopp and Gerald Henkel
b
c
*
´
¨
aLaboratory of Applied Synthetic Organic Chemistry, Department of Chemistry, Faculty of Science, University of Dschang,
PO Box 067 Dschang, Cameroon
bOrganische Chemie, Universitat Duisburg-Essen, 47057 Duisburg, Germany
¨
cChemie und Chemietechnik, Warburger Str. 100, Universitat Paderborn, 33098 Paderborn, Germany
¨
Received 27 December 2005; revised 29 March 2006; accepted 11 April 2006
Available online 26 May 2006
Dedicated to the memory of Dr. Emmanuel Nyiondi-Bonguen
Abstract—The reactivity of 2-aminothiophenes in two different anellations: (a) [b]-anellation to a saturated carbocycle and (b) [3,4-c]-anel-
lation to benzopyrans, towards typical acetylenic dienophiles has been investigated. Because of the absence of conjugation, the thiophenes of
type (a) do not undergo [4+2]-cycloaddition with acetylenic dienophiles. Instead, the N-vinylated products 2 and 3 were obtained with di-
methyl acetylene dicarboxylate (DMAD). Electron poor alkynes react with the thiophenes of type (b) in three main ways: DMAD reacts
in a [4+2]-mode in dioxane to give the products 7, 8 and 14; a Michael addition type reaction also takes place at the doubly vinylene homol-
ogous carbon atoms (C-1 in the starting materials 4, 9 and 10) in dioxane, methanol or ethanol. Methyl propiolate reacts in a similar way. The
doubly N-vinylated product 26 was obtained from 10 in toluene and the C-1 vinylated products 24B and 27 were obtained from 9 in dioxane
and 10 in methanol. The reaction of 10 with phenyl ethyl propiolate in dimethylformamide gave no addition product, instead a dimer of the
acetylenic reagent was the isolated product. The accuracy of the assigned structures 5, 12 and 13a could be achieved on the basis of a single-
crystal X-ray structure analysis of compound 13a. The reaction mechanism and the nature of the isolated products are dependent on the nature
of the solvent. No addition reaction was observed between 17 and DMAD. The influence of the N-substitution on the nature of the addition
(Michael or Diels–Alder) could be settled through the reactions of 18 and 21 with DMAD, which gave 19 and 14 (via 22), respectively as the
only isolable products.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
conditions gave the product 3. However, with 1f,g, no prod-
uct could be obtained under similar reaction conditions.
In previous studies,1–3a the reactivity of compound 4 towards
a variety of 1,3-dicarbonyl compounds (b-ketoesters and b-
diesters) and dienophiles like dimethyl maleate (or dimethyl
fumarate) and dimethyl acetylene dicarboxylate (DMAD)
was reported. We here report our investigations on the reac-
tivity of 2-aminothiophenes 1a–g, 4, 9, 103b and 173b towards
electron poor alkynes (DMAD, ethyl propiolate and ethyl
phenylpropiolate).
O
NH2
H
N
X
X = CONH2
n = 2
(CH2)n
O
(CH2)n
(CH2)n
NH2
S
S
OMe
O
3
1
MeOH
Reflux
+
X
H
N
E
E
E
H
E = COOCH3
S
E
2
2. Results
a
1,2
n
b
2
CN
c
d
e
f
g
1
2
2
2
3
3
The starting compounds were prepared using either the one-
pot (1a–g and 17) or the two-step procedures (4, 9 and 10) of
the Gewald method. Compounds 1a–d react with DMAD
under reflux in methanol to afford the N-vinylated products
2a–d (Scheme 1). Substrate 1e under similar reaction
CO2CH3
X
CO3CH3 COC2H5 CONH2 CN CONH2
Scheme 1.
The suggested structures agreed with the analytical and
spectroscopic data. The formation of compound 3 can well
be attributed to the polyfunctionality of substrate 1e. The
course of the reaction involves the formation of intermedi-
ates 3A and (after addition of water) 3B. The determining
Keywords: 2-Aminothiophenes; Angular anellation; Diels–Alder addition;
Electron poor acetylenes; Michael addition; retro-Aldol-reaction.
* Corresponding author. E-mail: sopbue@yahoo.fr
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.037

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E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7122
step is a Michael type addition followed by a retro-aldol like
elimination of methyl acetate (Scheme 2).
further supported by a single-crystal X-ray structure analysis
of 13a (Fig. 1). Although the compound exists in a stable
helical conformation in the crystal, the existence of stable
enantiomers in solution could not be proven (HPLC using
various chiral stationary phases). Rotation of the fumarate
moiety relative to the thiophene ring may cause rapid inter-
conversion of enantiomers.
O
O
O
H
NH2
E
NH2
N
E
E
E
N
S
N
H
CH2E
NH2
E
S
3A
S
H
H
1e
O
Compound 13a was further characterized by the prepara-
tion of its N-acyl derivatives 13b,c. The 1H-NOESY experi-
ment3b with 13b provided more supporting evidence for
the suggested structures 5, 12 and 13a. The observation of
1H-NOESY cross-peaks between the singlets at d¼3.36 ppm
(assigned to COOCH3 at C-3 in the fumarate moiety), the
singlet at d¼6.97 ppm (3-H), the doublet at d¼7.86 ppm
(60-H) and the overlapped ddd at 7.46 ppm (90-H and
100-H), points to the torsional flexibility of the fumarate
4-methoxy group in solution and to the proximity of the
fumarate moiety to C-90 and C-100.
O
O
NH2
H
H
H
N
N
H2O
E
N
E
S
N
H
N
O
S
3B
S
E
3
O
H
E = CO2CH3
Scheme 2.
In refluxing methanol or ethanol, compound 4 reacts with
DMAD to give the 1:3 addition product 5 (Scheme 3) as
a mixture (1:1) of two stereoisomers in 44% yield.
When compound 4 was treated with excess of DMAD under
reflux in dioxane, compound 5 was obtained in 21% yield af-
ter cooling in liquid nitrogen. The silica-gel chromatography
of the resulting filtrate gave 27% of compound 83b and 10%
of compound 7. Compound 8 can be quantitatively prepared
by reacting 9 with dimethyl maleate (or dimethyl fumarate).
Derivative 7 is conceivable from both precursors 6 and 8
(Scheme 3).
On the other hand, only one cross-peak is observed between
the singlet at d¼3.52 ppm (assigned to COOCH3 at C-2 in
the fumarate moiety) and the singlet at d¼6.97 ppm (3-H).
This is in agreement with the apparent remoteness of the car-
bomethoxy group at C-2 from the naphthalene ring system.
Besides a cross-peak between d¼2.41 ppm (s, COCH3) and
d¼11.03 ppm (br s, –NH–), another cross-peak is observed
between d¼2.41 ppm and d¼6.97 ppm (s, 3-H). This obser-
vation suggests a conformation in solution in which the
methyl protons are close to 3-H of the fumarate fragment.
Similarly all the conceivable isomeric thiepin derivatives
The key steps in both reaction routes could be considered as
6p-electrocyclizations of the intermediate 1:1 Michael ad-
ducts. Under the same reaction conditions as with 4, the sub-
strates 9 and 10, respectively, react with DMAD to afford
compounds 8 and 12 or 13a and 14, respectively (Scheme 4).
1
(e.g. 15 and 16) were ruled out on the basis of their H
and 13C(1H) NMR experimental and simulated spectral
data.3b
In the widest sense, the compounds 5, 12 and 13a can be con-
sidered as Michael addition products. These structures were
By reacting compound 9 with DMAD under reflux for 4 h,
Elnagdi et al.4 recently isolated a substance to which they
R
S
S
E
E
NH2
NH
NH-R
MeOH
Reflux
+
O
4
N
E
R
O
5
∆
Dioxane
E
E
N
E
5
+
NH2
E
O
H
O
NH
E
R =
7
6
E
E
SiO2.H2O
E = CO2CH3
E
E
S
E
E
NH2
neat /Reflux
-H2S
NH2
+
O
9
O
O
8
O
Scheme 3.

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E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7123
E
E
H
O
R2
C
S
E
E
R2
E
R1
MeOH
NH-R
S
S
+
R2
H
H
R1
NH-R
Reflux
R1
N
O
O
E
R
9 : R = R1 = R2 = H
O
10 : R = H, R1, R2 = C4H4
O
11
O
12 : R = R1 = R2 = H
13a : R = H, R1, R2 = C4H4
b : R = CH3CO, R1, R2 = C4H4
c : R = CF3CO, R1, R2 = C4H4
Dioxan
(reflux)
∆
E
E
E
NH-R
R2
-S
R2
S
R1
R1
12, 13a
NH-R
E
neat, reflux
(-H2S)
O
O
O
8 : R = R1 = R2 = H
14 : R = H, R1, R2 = C4H4 (96%)
O
9 : R = R1 = R2 = H
(72%)
E
E
R2
NH2
E = COOMe
R1
S
O
O
15 : R1 = R2 = H
16 : R1, R2 = C4H4
Scheme 4.
nevertheless products of a Diels–Alder addition of the ace-
tylene diester on the thiophene ring of 4 or 9 (Scheme 3).
It is also conceivable that the intermediate 12 cyclizes to
give such a [4+2]-adduct. In any case the newly constructed
benzene ring results from the extrusion of elemental sulfur
from this primary [4+2]-adduct (Scheme 4).
NC
CN
S
NH2
NC
17
Numerous attempts to induce a reaction between compound
17 and DMAD so far remain unsuccessful. The sluggishness
of the reaction of substrate 17 compared to other substrates
could partly be attributed to the push–pull effect, which
leads to the great stability of this substrate, and hence its
unreactivity towards dienophiles.
Figure 1. Single-crystal X-ray structure analysis of compound 13a.
The crystallographic numbering does not reflect the systematic IUPAC
numbering.
The assumption that the Michael type addition at C-1 in 4, 9
and 10 is favoured by the free NH2-group, prompted us to
study the reactions of the N-acylated products 18 and 21
towards DMAD. As anticipated, no Michael adduct was
observed in these reactions in refluxing DMF. The Diels–
Alder adducts 19 and 14 (through 22), respectively, were
the only isolable reaction products from substrates 18 and
21 in 42 and 11% yield (Scheme 5). The formation of com-
pound 14 certainly results from subsequent hydrolysis of the
acetamido group of the primarily formed but not isolable
cycloadduct 22. The low yields of 14 and 19 (<50% in
both cases) observed in these reactions suggests that N-acyl-
ation as in 18 and 21 drastically decreases the vinylation at
C-1 and allows the otherwise less competitive Diels–Alder
addition to gain importance.
assigned the structure of the thiepin 15, probably on the basis
of former reasoning.1,2,3a With a melting point of 162 ꢀC4
from ethanol (171–173 ꢀC from methanol for 12) and almost
identical analytical and spectroscopic data, we assume that
this compound is identical to 12 (Scheme 4). The formation
of compound 5 is the most complicated case and the
consequence of the polyfunctionality of the starting material
4: both amino and imino groups can add to the electron poor
triple bond. The fastest reaction is obviously the addition of
DMAD at the position 1 in 4, 9 and 10. It can be rationalized
in terms of attack on the doubly vinylene-homologous posi-
tion to the amino group. The known compounds 8 and 7 are

´
E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7124
E
E
R2
R2
S
R1
R1, R2 = C4H4
(a)
(b)
R1
NH-COCH3
NH-Ac
14
(1)
(2)
(3)
O
O
O
O
19 : R1 = R2 = H
Dioxane
Reflux
[22 : R1, 2 = C4H4
]
18 : R1 = R2 = H
21 : R1, R2 = C4H4
+
R
E
H
E
E
E
R2
S
R1
NHCOCH3
O
O
20 : R1 = R2 = H
[23 : R1, R2 = C4H4
]
S
S
E
NH-COCH3
E
E
(-S)
NH-Ac
NH
+
Ac
E
E
E
Scheme 5.
E
Also the reaction of substrate 9 with methyl propiolate under
reflux in dioxane gave 73% yield the Michael type 1:1
adducts 24 and 25 (Scheme 6) as a 13:1 mixture.
H
S
H
H
N
Toluene
Reflux
H
O
By reacting compound 10 with methyl propiolate in reflux-
ing toluene, the N,N-divinylation product 26 (Scheme 7) was
the isolated product in 70% yield. The structure of 26 re-
sulted from analytical and spectroscopic data.
O
26
E
S
E
NH2
+
E
H
O
10
O
H
H
S
When the reaction was carried out in refluxing methanol, a
yellow substance melting at 312–314 ꢀC was isolated, to
which structure 27 (Scheme 7) was assigned on the basis of
IR- and mass-spectroscopic data. The reaction of 10 with
ethyl phenylpropiolate gave neither a cycloaddition, nor a
Michael addition product. The dimerization product 28
MeOH
Reflux
NH2
O
27
O
Scheme 7.
E
H
H
S
E
H
H
E
1'
NH2
S
S
S
2'
NH2
NH2
NH2
O
9
O
Dioxane
Reflux
O
O
H
O
O
O
O
+
E
H
24A
E
H
2'
2'
C
C
E
H
C
1'
H
C
S
1'
S
H
H
N
N
H
H
O
O
O
25
O
24B
Scheme 6.

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E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7125
Ph
E
and AMD 604 instruments by electron impact ionization
(EI) at 18 eVor 70 eV, using a direct inlet system. Combus-
tion analyses were carried out with a CHN+O/S elemental
analyzer ‘CARLO ERBA’ Model 1106. Simulated H and
13C(1H) NMR spectra were performed with an ACD NMR
spectra simulation programme.
No addition product
S
DMF
NH2
1
+
Reflux
O
10
O
CO2C2H5
CO2C2H5
28
E = CO2C2H5
4.1. Gewald synthesis of 2-aminothiophenes
Scheme 8.
4.1.1. Variant A (one-pot procedure)7–11 general pro-
cedure. To an equimolar (if not otherwise stated) mixture
of ketone, nitrile and finely powdered elemental sulfur in eth-
anol (if not otherwise stated) the indicated amount of diethyl-
amine, piperidine or morpholine is slowly added with
magnetic stirring, so that the temperature does not exceed
50 ꢀC. By warming, sulfur progressively dissolves. For
a slower reaction one should warm periodically up to 40–
50 ꢀC (water bath). Continued warming bears the risk of
the formation of the disulfide.7–11 The reaction lasts for 4–
6 h in total. The reaction mixture is kept in the refrigerator
for crystallization for several hours, after which the precipi-
tate is collected and worked up as indicated. If not otherwise
stated, the given yields are based on the inputs of ketone.
(Scheme 8) of the acetylene was instead the isolated com-
pound from this reaction.
3. Conclusions
The reactions of 2-aminothiophenes with electron poor
alkynes described in this work are of following types: (i) con-
jugate additions to the amino- or imino groups; (ii) conjugate
additions at C-1 of the thienocoumarin derivatives 4, 9 and
10; (iii) formation of an anellated benzene ring across the
3,4-double bond of the coumarin derivative, very probably
through a [4+2]-cycloaddition with subsequent desulfura-
tion. One could also, in principle, envisage that the formal
[4+2]-cycloaddition can also take place stepwise. The cases
found by Elnagdi et al.4 also fit in Scheme 9. The successful
cycloadditions encountered in this work are normal5 Diels–
Alder reactions, in which the diene HOMO/dienophile-
LUMO is the predominant interaction. They can therefore
be rationalized by perturbation theory.5,6
4.1.1.1. Methyl 2-amino-5,6-dihydro-4H-cyclopenta-
[b]thiophene-3-carboxylate (1a). From cyclopentanone
(33.60 g, 0.4 mol), methyl cyanoacetate (19.80 g, 0.2 mol),
powdered sulfur (3.2 g, 0.1 mol) and piperidine (8.50 g,
0.1 mol), the reaction lasted for 8 h. Crystallization from
methanol gave the title compound 1a (13.91 g, 35% based
on the nitrile) as yellow powder, mp 181–183 ꢀC [Found:
C, 54.73; H, 5.54; N, 7.05; S, 16.45. C9H11NO2S requires
C, 54.82; H, 5.58; N, 7,11; S, 16.24%]; nmax (potassium
bromide) 3410, 3293, 3163, 3076, 2967, 2944, 2857,
1654 cmꢁ1; dH (300 MHz, CDCl3) 5.86 (2H, br s, D2O-
exchangeable, NH2), 3.78 (3H, s, OMe), 2.83–2.77 (2H, m,
4-H2), 2.74–2.68 (2H, m, 6-H2), 2.35–2.26 (2H, m, 5-H2);
dC (75 MHz, CDCl3) 166.5, 166.1, 142.6, 121.4, 102.8,
50.6, 30.7, 28.8, 27.3; m/z (EI) 198 (5), 197 (49, M+), 167
(5), 166 (15), 165 (100), 164 (12%).
R
E
R
E
S
- S
R
E
NH2
NH2
S
+
R
H
E
R
NH2
C
C
E
H
S
S
NH2
N
H
4.1.1.2. 2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophen-
3-carbonitrile (1b). From cyclohexanone (29.4 g, 0.3 mol),
malononitrile (13.20 g, 0.2 mol), powdered sulfur (6.4 g,
0.2 mol) and diethylamine (7.3 g, 0.1 mol) in ethanol, the
reaction was conducted for 2 h. Crystallization from 50%
aqueous ethanol gave the title compound 1b (29.94 g, 84%)
as yellow powder, mp 144–146 ꢀC (lit.,10 147–148 ꢀC from
ethanol) [Found: C, 60.68; H, 5.64; N, 15.67; S, 17.96.
C9H10N2S requires C, 60.67; H, 5.64; N, 15.67; S,
17.96%]; nmax (potassium bromide) 3446, 3330, 3207, 2956,
2932, 2911, 2854, 2838, 2744, 2667, 2649, 2198 cmꢁ1; dH
(300 MHz, CDCl3) 4.41 (2H, br s, D2O-exchangeable,
NH2), 2.55–2.43 (4H, m, 4-H2 and 7-H2), 1.86–1.72 (4H,
m, 5-H2 and 6-H2); dC (75 MHz, CDCl3) 160.0, 132.4,
120.7, 115.5, 88.8, 24.6, 24.2, 23.4, 22.2; m/z (EI) 179 (6),
178 (49, M+), 177 (15), 151(10), 150 (100%).
H
S
S
E
N
E
N
H
R
E
R
R
Scheme 9.
4. Experimental
All elemental and spectroscopic analyses were performed in
the Chemistry Department Analytical Center of Gerhard-
Mercaptor-Universitat Duisburg, Duisburg (Germany). All
¨
melting points were determined with a Reichert Thermovar
microscope and are uncorrected. The IR and the UV spectra
were measured with Perkin–Elmer 983 and 554 spectropho-
tometers, respectively. 1H and 13C(1H) NMR spectra were re-
corded on Bruker WM 300 and DRX 500 instruments, with
TMS as internal standard. Coupling constants J are reported
in Hertz. Mass spectra were obtained on Varian MAT 311A
4.1.1.3. Methyl 2-amino-4,5,6,7-tetrahydrobenzo[b]-
thiophene-3-carboxylate (1c). From cyclohexanone
(29.4 g, 0.3 mol), methyl cyanoacetate (19.18 g, 0.2 mol),
sulfur (6.40 g, 0.2 mol) and diethylamine (8.50 g, 0.1 mol),
the reaction was conducted for 9.5 h. The precipitate was

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7126
crystallized from methanol/water (75:25) to give the title
compound 1c (29.34 g, 70%) as yellow powder; mp 128–
130 ꢀC (lit.,12 127–128 ꢀC from methanol) [Found: C,
56.92; H, 6.20; N, 6.62; S, 15.27. C10H13NO2S requires C,
56.87; H, 6.16; N, 6.64; S, 15.17%]; nmax (potassium bro-
mide) 3421, 3315, 3157, 3013, 2929, 2837, 1653 cmꢁ1; dH
(300 MHz, CDCl3) 5.95 (2H, br s, D2O-exchangeable,
NH2), 3.78 (3H, s, OMe), 2.70–2.63 (2H, m, 7-H2), 2.52–
2.46 (2H, m, 4-H2), 1.81–1.68 (4H, m, 6-H2 and 5-H2); dC
(75 MHz, CDCl3) 166.5, 161.9, 132.5, 117.7, 105.7, 50.6,
26.9, 24.6, 23.3, 22.8; m/z (EI) 212 (7), 211 (52, M+), 183
(3), 181 (6), 180 (16), 179 (100%).
(75 MHz, CDCl3) 158.1, 136.9, 123.8, 115.9, 91.9, 31.9,
29.4, 29.2, 28.1, 27.3; m/z (EI) 194 (5), 193 (15), 192
(100%, M+).
4.1.1.7. 2-Amino-5,6,7,8-tetrahydro-4H-cyclohepta-
[b]thiophene-3-carboxamide (1g). From cycloheptanone
(5.60 g, 50 mmol), cyanoacetamide (4.2 g, 50 mmol), sulfur
(1.6 g, 50 mmol) and piperidine (4.25 g, 50 mmol) in etha-
nol, the reaction was conducted for 5 h and the resulting pre-
cipitate was crystallized from 50% aqueous ethanol to give
the title compound 1g (5.01 g, 48% based on the nitrile) as
red powder, mp 154–156 ꢀC (lit.,14 183–186 ꢀC from etha-
nol); nmax (potassium bromide) 3375, 3198, 2915, 2844,
1630 cmꢁ1; dH (CDCl3, 300 MHz) 6.79 (2H, br s, D2O-ex-
changeable, CONH2), 6.02 (2H, br s, D2O-exchangeable,
NH2), 2.68–2.48 (4H, m, 4-H2 and 8-H2), 1.73–1.50 (6H,
m, 5-H2, 6-H2 and 7-H2); dC (CDCl3, 75 MHz) 167.9,
153.6, 136.4, 120.1, 113.5, 31.7, 28.6, 28.3, 27.8, 27.2; m/z
(EI) 210 (44, M+), 194 (14), 193 (100), 192 (7), 178 (4),
172 (4), 166 (4), 165 (19), 164 (11), 45 (4), 44 (4%).
4.1.1.4. Ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]-
thiophene-3-carboxylate (1d). From cyclohexanone
(29.4 g, 0.3 mol) ethylcyanoacetate (11.30 g, 0.1 mol), sul-
fur (3.20 g, 0.1 mol) and piperidine (4.25 g, 0.05 mol), the re-
action lasted for 9 h and the precipitate was crystallized from
50% aqueous ethanol to give the title compound 1d (15.76 g,
70%) as yellow powder, mp 117–118 ꢀC (lit.,10 115 ꢀC
from methanol) [Found: C, 58.63; H, 6.60; N, 6.30; S,
14.35. C11H15NO2S requires C, 58.67; H, 6.67; N, 6.22; S,
14.22%]; nmax (potassium bromide) 3405, 3300, 3230,
3167, 3077, 2986, 2939, 2886, 2855, 2841, 1643 cmꢁ1; dH
(300 MHz, CDCl3) 5.97 (2H, br s, D2O-exchangeable, NH2),
4.24 (2H, q, J 7.1 Hz, OCH2CH3), 2.71–2.66 (2H, m, 7-
H2), 2.49–2.45 (2H, m, 4-H2), 1.79–1.67 (4H, m, 6-H2 and
5-H2), 1.37 (3H, t, J 7.1, OCH2CH3); dC (75 MHz, CDCl3)
166.2, 161.8, 132.5, 117.6, 105.8, 59.4, 27.0, 24.6, 23.32,
22.9, 14.5; m/z (EI) 227 (5), 226 (11), 225 (70, M+), 197
(3), 181(10), 180 (29), 179 (100%).
4.1.1.8.
3-Amino-4H-thieno[3,4-c](2H)chromen-4-
one (9). A mixture of o-hydroxyacetophenone (27.2 g,
200 mmol), sulfur (6.4 g, 200 mmol) and ethylcyanoacetate
(22.6 g, 200 mmol), or methyl cyanoacetate (19.8 g,
200 mmol), respectively in methanol (200 mL) in the pres-
ence of morpholine or diethylamine, was stirred for 24 h.
The precipitate was crystallized from benzene to give the
title compound 9 (16 g, 37%) as yellow powder, mp 197–
199 ꢀC (lit.,15a,b 198–199 ꢀC from benzene) [Found: C,
61.17; H, 3.36; N, 6.49; S, 14.45. C11H7NO2S requires C,
60.83; H, 3.23; N, 6.45; S, 14.75%]; nmax (potassium bro-
mide) 3449, 3407, 3343, 3101, 1687 cmꢁ1; dH (DMSO-d6,
300 MHz) 7.86 (6-H, dd, J 8.0, 1.5 Hz, 1H), 7.78 (2H, br
s, D2O-exchangeable, NH2), 7.35 (1H, ddd, J 8.0, 7.4,
1.8 Hz, 7-H), 7.21 (1H, d, J 7.0 Hz, 9-H), 7.19 (1H, ddd, J
8.2, 7.6, 1.2 Hz, 8-H), 6.88 (1H, s, 1-H); dC (DMSO-d6,
75 MHz) 166.6 (C-3), 158.9 (C-2), 151.0, 130.9, 129.3,
124.4, 123.9, 118.1, 117.1, 98.1, 97.54; m/z (EI) 219 (6),
218 (13), 217 (100%, M+).
4.1.1.5.
2-Amino-4,5,6,7-tetrahydrobenzo[b]thio-
phene-3-carboxamide (1e). From cyclohexanone (3.92 g,
40 mmol), cyanoacetamide (3.36 g, 80 mmol), sulfur
(1.28 g, 40 mmol) and piperidine (2.92 g, 35 mmol), the re-
action was carried out for 7 h and the precipitate was crystal-
lized from 50% aqueous ethanol to givethe title compound 1e
(3.54 g, 45% based on the nitrile) as yellow powder, mp 180–
181 ꢀC (lit.,10 189–190 ꢀC from methanol) [Found: C, 55.04;
H, 6.08; N, 14.15; S, 16.40. C9H12N2OS requires C, 55.10; H,
6.12; N, 14.27; S, 16.34%]; nmax (potassium bromide) 3482,
4.1.1.9. 3-Acetamido-4H-thieno[3,4-c](2H)chromen-
4-one (18). From 9 (2.17 g, 10 mmol) and acetic acid anhy-
dride (20 mL) in pyridine at room temperature, the reaction
lasted for 48 h and the precipitate was crystallized from pyr-
idine to give the title compound 18 (2.21 g, 85%) as yellow
crystals, mp 268–270 ꢀC [Found: C, 60.19; H, 3.50; N,
5.57; S, 12.44. C13H9NO3S requires C, 60.23; H, 3.47; N,
5.41; S, 12.36%]; nmax (potassium bromide) 3465, 3299,
3100, 1678 cmꢁ1; dH (DMSO-d6, 300 MHz) 10.9 (1H, br s,
D2O-exchangeable, NH), 8.03 (1H, dd, J 7.7, 1.6 Hz, 6-H),
7.69 (1H, s, 1-H), 7.44 (1H, ddd, J 7.0, 6.9, 1.6 Hz, 7-H),
7.34 (1H, dd, J 7.9, 1.2 Hz, 9-H), 7.32 (1H, ddd, J 7.5, 7.2,
1.4 Hz, 8-H), 2.33 (3H, s, CH3); dC (DMSO-d6, 75 MHz)
168.8, 158.6, 150.2, 149.9, 130.1, 129.8, 125.1, 124.3,
117.3, 117.1, 108.6, 105.8, 23.2; m/z (EI) 260 (4), 259 (25,
M+), 219 (6), 218 (14), 217 (100), 189 (4), 44 (12), 43 (23%).
3387, 3305, 3153, 2939, 1642, 1311, 1281, 1258, 1185 cmꢁ1
;
dH (300 MHz, CDCl3) 5.55 (4H, br s, D2O-exchangeable,
NH2), 2.39–2.33 (4H, m, 4-H2 and 7-H2), 2.28–2.26 (4H,
m, 5-H2 and 6-H2); dC (75 MHz, CDCl3) 168.4, 160.6,
129.2, 117.7, 107.1, 26.8, 24.4, 22.8, 22.8; m/z (EI) 198 (4),
197 (9), 196 (67, M+), 181 (8), 180 (17), 179 (100%).
4.1.1.6. 2-Amino-5,6,7,8-tetrahydro-4H-cyclohepta-
[b]thiophene-3-carbonitrile (1f). From cycloheptanone
(16.8 g, 150 mmol), malononitrile (6.6 g, 100 mmol), sulfur
(3.2 g, 100 mmol) and piperidine (4.25 g, 50 mmol) in etha-
nol, the reaction lasted for 6 h. Crystallization from 50%
aqueous ethanol gave the title compound 1f (12.09 g, 67%
based on the nitrile) as brown powder, mp 115–117 ꢀC
(lit.,13 114 ꢀC from ethanol) [Found: C, 62.38; H, 6.21; N,
14.39; S, 16.86. C10H12N2S requires C, 62.50; H, 6.25; N,
14.58; S, 16.67%]; nmax (potassium bromide) 3445, 3310,
3208, 2927, 2840, 2205 cmꢁ1; dH (300 MHz, CDCl3) 4.57
(2H, br s, D2O-exchangeable, NH2), 2.68–2.60 (4H, m,
8-H2), 2.59–2.51 (2H, m, 4-H2), 1.86–1.78 (1H, m, 7-H2),
1.68–1.65 (2H, m, 5-H2), 1.64–1.60 (2H, m, 6-H2); dC
4.1.1.10. 2-Amino-4-(dicyanomethylene)-4H-indeno[2,
3-b]thiophene-1-carbonitrile (17). From indan-1,3-dione
(1.46 g, 10 mmol), malononitrile (1.32 g, 20 mmol), sulfur
(0.32 g, 20 mmol) and diethylamine (1.46 g, 20 mmol) in
dioxane, the reaction was conducted for 6 h and the resulting

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E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7127
precipitate was crystallized from dioxane to give the title
compound 17 (1.84 g, 67%) as deep blue powder,
mp>350 ꢀC [Found: C, 65.53; H, 2.24; N, 20.30; S, 11.73.
C15H6N4S requires C, 65.69; H, 2.19; N, 20.44; S, 11.68%];
nmax (potassium bromide) 3365, 3182, 2951, 2855,
2219 cmꢁ1; lmax (dioxane) (log 3) 240 (4.32), 280 (4.14),
380 (4.14), 540 nm (3.78); dH (DMSO-d6, 300 MHz) 9.24
(2H, br s, D2O-exchangeable, NH2), 7.71 (1H, d, J 6.9 Hz,
5-H), 7.35 (1H, ddd, J 7.4, 7.3, 1.1 Hz, 6-H), 7.29 (1H, dd,
J 7.54, 1.25 Hz, 8-H), 7.23 (1H, ddd, J 7.7, 7.0, 0.7 Hz,
7-H); dC (DMSO-d6, 75 MHz) 176.2, 154.9, 153.9, 137.6,
134.8, 132.1, 129.5, 123.8, 120.1, 114.9, 114.1, 113.9,
113.0, 80.3, 63.8; m/z (EI) 275 (35, MH+), 274 (100%, M+).
129.0, 128.4, 128.2, 125.3, 124.2, 117.4, 111.2, 110.6,
106.6, 22.9; m/z (EI) 311 (4), 310 (11), 309 (M+, 54), 269
(6), 268 (19), 267 (100), 44 (6%).
4.1.3. Reactions of 2-aminothiophenes with acetylenic
reagents general procedure. An equimolar amount (1–
2.5 mmol, if not specified otherwise) of the 2-aminothio-
phene and the electron poor acetylene in the given solvent
was refluxed with magnetic stirring for 3–10 h (if not spec-
ified otherwise). The reaction mixture was worked up as
usual and the product was purified as described for each par-
ticular substance. The unoptimized yields are based on the
amounts of reacted 2-aminothiophene.
4.1.2. Variant B (two-step procedure)7–11. Compounds
4,15a,b 915a,b and 10 were prepared according to the two-
step procedure of the Gewald method, in the reported yields.
4.1.3.1. Dimethyl (E,Z){N-[2-(3-methoxycarbonyl-5,6-
dihydro-4H-cyclopenta[b]thienyl)]amino}butenedioate
(2a). From a mixture of 1a (0.50 g, 2.5 mmol) and DMAD,
(1.42 g, 10 mmol) in methanol, the reaction was conducted
for 9.5 h and the precipitate was crystallized from methanol
to give the title compound 2a (700 mg, 81%) as yellow
needles, mp 94–96 ꢀC. The remaining oily fraction was dis-
carded analyzed [Found: C, 53.01; H, 4.90; N, 3.98; S, 9.30.
C15H17NO6S requires C, 53.10; H, 5.01; N, 4.13; S, 9.44%];
nmax (potassium bromide) 3444, 3150, 3023, 2947, 2860,
1731, 1697, 1685 cmꢁ1; dH (CDCl3, 300 MHz) 11.56 (1H,
br s, D2O-exchangeable, NH), 5.44 (1H, s, ]CH), 3.87
(3H, s, OMe), 3.86 (3H, s, OMe), 3.78 (3H, s, OMe), 2.91–
2.81 (2H, m, 40-H2), 2.79–2.76 (2H, m, 60-H2), 2.39–2.29
(2H, m, 50-H2); dC (CDCl3, 75 MHz) 168.3, 164.8, 164.1,
154.8, 144.6, 143.4, 128.4, 110.1, 96.8, 53.2, 51.6, 51.5,
30.6, 29.1, 27.4; m/z (EI) 342 (7), 340 (18), 339 (100, M+),
44 (3%).
4.1.2.1. 3-Amino-4-imino-4H-thieno[3,4-c](2H)chrom-
ene (4). Yellowish powder from benzene, mp 158–160 ꢀC,
from xylene (lit.,15a,b 152 ꢀC from xylene) [Found:
C, 61.07; H, 3.74; N, 12.97; S, 14.79. C11H8N2OS requires
C, 61.09; H, 3.73; N, 12.95; S, 14.83%]; nmax (potassium
bromide) 3382, 3276, 3108, 3057, 1630, 1589, 1475, 1355,
1292, 1179, 1099, 932, 877, 792 cmꢁ1; lmax (dioxane)
(log 3) 200 (4.88), 228 (5.31), 267 (5.37), 305 nm (4.80);
dH (DMSO-d6, 300 MHz) 7.87 (1H, br s, D2O-exchangeable,
]NH), 7.77 (1H, dd, J 7.7, 1.6 Hz, 9-H), 7.69 (2H, br s,
D2O-exchangeable, NH2), 7.26 (1H, ddd, J 8.1, 7.0,
1.6 Hz, 7-H), 7.1 (1H, ddd, J 14.4, 8.2, 1.3 Hz, 8-H), 7.1
(1H, dd, J 8.1, 1.1 Hz, 6-H), 6.8 (1H, s, 1-H); dC (DMSO-
d6, 75 MHz) 160.7, 155.1, 150.7, 129.7, 129.0, 123.9,
123.5, 118.3, 116.3, 99.7, 97.2; m/z (EI) 218 (6), 217 (16),
216 (M+, 100), 215 (33), 199 (5), 77 (7%).
4.1.3.2. Dimethyl (E,Z)-2{N-[2-(3-cyano-4,5,6,7-tetra-
hydrobenzo[b]thienyl)]amino}butenedioate (2b). From
1b (450 mg, 2.5 mmol) and DMAD (1.42 g, 10 mmol) in
methanol, the reaction was carried out for 9 h. The reaction
mixturewas concentrated invacuo and the resulting oily resi-
due was kept in the refrigerator for few days. Crystallization
of the solid from methanol gave the title compound 2b
(273 mg, 34%) as yellow needles, mp 117–118 ꢀC. The
mother liquor was discarded [Found: C, 56.14; H, 4.92; N,
8.67; S, 10.25. C15H16N2O4S requires C, 56.25; H, 5.00; N,
8.75; S, 10.00%]; nmax (potassium bromide) 3447, 3187,
3095, 2950, 2935, 2859, 2212, 1734, 1672 cmꢁ1; dH
(CDCl3, 300 MHz) 9.90 (1H, br s, D2O-exchangeable,
NH), 5.69 (1H, s, (COOMe)CH]), 3.83 (3H, s, COOMe),
3.77 (3H, s, COOMe), 2.63–2.57 (4H, m, 40-H2 and 70-H2),
1.87–1.78 (4H, m, 50-H2 and 60-H2); dC (CDCl3, 75 MHz):
169.5, 162.8, 150.3, 146.1, 133.8, 130.2, 102.0, 97.5, 53.2,
51.7, 24.5, 24.4, 23.0, 22.0; m/z (EI) 322 (4), 321 (9), 320
(51, M+), 289 (10), 288 (44), 262 (10), 261 (37), 260 (100),
59 (5), 45 (3), 32 (46%).
4.1.2.2. 3-Amino-4H-benzo[f]thieno[3,4-c](2H)chro-
men-4-one (10). Yellow prisms from benzene, mp 235–
237 ꢀC [Found: C, 67.36, H, 3.43; N, 5.28; S, 11.90.
C15H9NO2S requires C, 67.42; H, 3.37; N, 5.24; S, 11.99%];
nmax (potassium bromide) 3439, 3335, 3137, 1690 cmꢁ1
;
dH (DMSO-d6, 300 MHz) 8.69 (1H, d, J 8.5 Hz, 6-H), 8.33
(2H, br dd, J 8.1, 1.2 Hz, H-8 and H-11), 7.93 (2H, br s,
D2O-exchangeable, NH2), 7.68 (1H, ddd, J 8.5, 7.0,
1.5 Hz, 10-H), 7.55 (1H, ddd, J 7.5, 7.4, 0.8 Hz, 9-H), 7.40
(1H, d, J 8.9 Hz, 7-H), 7.33 (1H, s, 1-H); dC (DMSO-d6,
75 MHz) 165.8, 159.0, 150.4, 130.8, 130.5, 129.6, 129.4,
129.3, 128.3, 125.3, 124.5, 117.9, 111.6, 101.2, 99.4; m/z
(EI) 269 (6, MH+2), 268 (17, MH+), 267 (100%, M+).
4.1.2.3. 3-Acetamido-4H-benzo[f]thieno[3,4-c](2H)-
chromen-4-one (21). Compound 10 (0.224 g, 0.84 mmol)
was treated with acetic acid anhydride (3.5 mL) in pyridine
at room temperature for 48 h and gave the title compound
21 after crystallization from pyridine (0.13 g, 85%) as yellow
prisms, mp 286–288 ꢀC [Found: C, 66.17; H, 3.62; S, 4.53; S,
10.26. C17H11NO3S requires C, 66.02; H, 3.56; N, 4.53; S,
10.36%]; nmax (potassium bromide) 3445, 3272, 1696,
1671 cmꢁ1; dH (DMSO-d6, 300 MHz) 10.98 (1H, br s, D2O-
exchangeable, NH), 8.82 (1H, d, J 8.42 Hz, 6-H), 8.0 (2 H, br
d, J 8.5 Hz, 8-H and 11-H), 7.75 (1H, dd, J 7.8, 7.7 Hz, 10-H),
7.61 (1H, dd, J 7.4, 7.3 Hz, 9-H), 7.51 (1H, d, J 8.8 Hz, 7-H),
8.09 (1H, s, 1-H), 2.36 (3H, s, COMe); dC (DMSO-d6,
75 MHz) 168.2, 158.3, 149.2, 149.2, 130.8, 130.6, 129.1,
4.1.3.3. Dimethyl (E,Z)-2-{N-[2-(3-methoxycarbonyl-
4,5,6,7-tetrahydrobenzo[l]thienyl)]amino}butenedioate
(2c). From a mixture of 1c (0.53 g, 2.5 mmol) and DMAD
(1.42 g, 10 mmol) in methanol, the reaction lasted for 10 h
and the resulting precipitate was crystallized from aqueous
methanol to afford the title compound 2c (742 mg,
84%) as yellow needles, mp 107–109 ꢀC. The mother liquor
was discarded. [Found: C, 54.35; H, 5.42; N, 3.95; S, 9.34.
C10H13NO2S requires C, 54.39; H, 5.38; N, 3.97; S,

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E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7128
9.07%]; nmax (potassium bromide) 3450, 3269, 3130, 3034,
3000, 2948, 2844, 1735, 1681 cmꢁ1; dH (CDCl3, 300 MHz)
11.62 (1H, br s, D2O-exchangeable, NH), 5.43 (1H, s, 3-H),
3.88 (3H, s, OMe), 3.87 (3H, s, OMe), 3.78 (3H, s, OMe),
2.77–2.63 (2H, m, 70-H2), 2.59–2.55 (2H, m, 40-H2), 1.83–
1.71 (4H, m, 60-H2 and 50-H2); dC (CDCl3, 75 MHz) 168.3,
165.0, 164.3, 150.4, 145.0, 133.4, 124.5, 113.2, 97.1, 53.3,
51.6, 51.4, 26.6, 24.7, 23.0, 22.6; m/z (EI) 353 (64, M+),
321 (32), 293 (21), 234 (100), 44 (4%).
[Found: C, 54.20; H, 4.01; N, 4.38; S, 5.04. C29H26N2O13S
requires C, 54.21; H, 4.05; N, 4.36; S, 4.98%]; nmax (potas-
sium bromide) 3433, 2953, 1725, 1661 cmꢁ1; lmax (THF)
(log 3) 252 (3.28), 292 (3.19), 322 (3.11), 368 (3.06),
400 nm (3.01); dH (500 MHz, CDCl3) 12.16 (1H, br s, NH,
D2O-exchangeable), 11.81 (1H, br s, NH, D2O-exchange-
able), 7.46 (1H, dd, J 7.9, 1.3 Hz, 9-H), 7.40 (1H, ddd, J
8.0, 7.9, 1.5 Hz, 7-H), 7.35 (1H, s, olefinic H), 7.29 (1H,
ddd, J 11.7, 8.9, 1.4 Hz, 8-H), 7.28 (1H, s, olefinic H), 7.25
(1H, dd, J 7.8, 1.1 Hz, 6-H), 7.12 (1H, ddd, J 7.7, 7.6,
1.0 Hz, 7-H), 7.08 (1H, dd, J 6.9, 1.0 Hz, 9-H), 7.05 (1H,
dd, J 9.2, 2.1 Hz, 6H), 7.06 (1H, ddd, J 7.0, 6.2, 1.8 Hz,
8-H), 6.45 (1H, s, olefinic H), 6.35 (1H, s, olefinic H), 5.83
(1H, s, olefinic H), 5.66 (1H, s, olefinic H), 3.95 (3H, s,
OMe), 3.90 (3H, s, OMe), 3.84 (3H, s, OMe), 3.75 (3H,
s, OMe), 3.73 (s, 3H, OMe), 3.71 (3H, s, OMe), 3.70 (3H,
s, OMe), 3.692 (3H, s, OMe), 3.689 (3H, s, OMe), 3.65
(3H, s, OMe); dC (125 MHz, CDCl3) 166.7, 166.3, 165.6,
165.5, 165.4, 164.7, 164.5, 164.3, 164.2, 163.8, 151.7,
150.5, 150.4, 150.3, 150.1, 148.9, 144.9, 144.6, 143.3,
142.2, 136.4, 136.3, 134.2, 133.6, 129.7, 129.3, 124.6,
124.5, 124.2, 116.9, 116.8, 112.8, 112.1, 101.8, 97.2,
128.1, 127.7, 117.9, 117.6, 112.4, 111.7, 107.9, 107.8,
53.6, 53.5, 53.3, 53.3, 52.9, 52.9, 52.5, 52.3, 51.7, 51.6,
51.5, 51.4; m/z (EI) 642 (27, M+), 585 (28), 583 (70), 552
(17), 551 (26), 425 (89), 366 (49), 334 (12), 307 (26), 248
(10), 154 (100), 59 (67), 44 (16%).
4.1.3.4. (E or Z) Dimethyl 2-{N-[2-(3-ethoxycarbonyl-
4,5,6,7-tetrahydrobenzo[b]thienyl)]amino}butenedioate
(2d). A mixture of 1d (0.56 g, 2.5 mmol) and DMAD
(1.42 g, 10 mmol) in methanol gave after 10 h of reaction
a precipitate, which was crystallized from methanol to
give the title compound 2d (3.43 g, 38%) as yellow needles,
mp 82–84 ꢀC. The oily mother liquor was discarded. [Found:
C, 55.60; H, 5.60; N, 3.84; S, 9.07. C17H21NO6S requires C,
55.59; H, 5.72; N, 3.80; S, 8.72%]; nmax (potassium
bromide) 3450, 3232, 3029–2843, 1736, 1673 cmꢁ1; dH
(CDCl3, 300 MHz) 11.56 (1H, br s, D2O-exchangeable,
NH), 5.41 (1H, s, ]CH), 4.35 (2H, q, J 7.1 Hz,
OCH2CH3), 3.84 (3H, s, OMe), 3.75 (3H, s, OMe), 2.75–
2.57 (2H, m, 70-H2), 2.56–2.53 (2H, m, 40-H2), 1.80–1.71
(4H, m, 60-H2 and 50-H2), 1.35 (3H, t, J 7.1 Hz,
OCH2CH3); dC (CDCl3, 75 MHz) 168.2, 164.6, 164.2,
150.3, 144.9, 133.3, 124.5, 113.5, 97.1, 60.3, 53.2, 51.5,
26.6, 24.6, 22.9, 22.6, 14.3; m/z (EI) 367 (95, M+), 335
(37), 307 (25), 276 (15), 262 (100%).
4.1.4.2. Tetramethyl 4-aza-7-oxabenz[m,n]anthra-
cene-2,3,5,6-tetracarboxylate (7). The reaction of 4
(0.54 g, 2.5 mmol) and DMAD (3 mL, excess) in dioxane
for 10 h, gave a mixture from which compound 5 (325 mg,
21%) gently separated on ice-cooling (freezer), for few
days. The mother liquor residue was subjected to plc (sol-
vent: hexane/ethyl acetate 7:3) to afford compound 8
(220 mg, 27%) as red needles (mp 201–203 ꢀC from metha-
nol); the title compound 7 (110 mg, 10%) as yellow needles
(mp 268–270 ꢀC, from aqueous DMF); compound 9 as yel-
low powder (mp 197–199 ꢀC, from benzene) and the non-re-
acted DMAD [Found: C, 62.09; H, 4.13; N, 4.30. C23H17NO9
requires C, 62.39; H, 3.98; N, 4.28%]; nmax (potassium
bromide) 3005, 2953, 1746, 1726 cmꢁ1; dH (500 MHz,
DMSO-d6) 8.48 (1H, s, 1-H), 8.33 (1H, dd, J 8.5, 1.6 Hz,
8-H), 7.61 (1H, ddd, J 8.3, 7.3, 1.5 Hz, 9-H), 7.43 (1H,
ddd, J 7.4, 7.3, 1.0 Hz, 10-H), 7.42 (1H, dd, J 9.4, 1.1 Hz,
11-H), 3.97 (3H, s, COOMe), 3.96 (3H, s, COOMe), 3.93
(3H, s, COOMe), 3.92 (3H, s, COOMe); dC (125 MHz,
DMSO-d6) 166.1, 164.7, 164.6, 163.3, 156.3, 151.0, 149.8,
144.8, 132.2, 132.0, 131.0, 128.7, 125.8, 124.1, 118.4,
117.9, 117.6, 115.8, 109.7, 53.0, 52.9, 52.6, 52.3; m/z (EI)
451 (83, M+), 421 (10), 420 (39), 406 (8), 393 (4), 392
(13), 374 (6), 335 (100%).
4.1.3.5. Methyl {N-[2-(3-aminocarbonyl-4,5,6,7-tetra-
hydrobenzo[b]thienyl)]}oxamate (3). From a mixture of
1e (0.50 g, 2.5 mmol) and DMAD (1.42 g, 10 mmol) in
methanol, the reaction was carried out for 9 h and the result-
ing precipitate was crystallized from methanol to give the
title compound 3 (95 mg, 13%) as yellowish powder, mp
218–220 ꢀC. The remaining oilish mixture was not further
analyzed [Found: C, 51.12; H, 4.98; N, 9.83; S, 11.50.
C12H14N2O4S requires C, 51.06; H, 4.96; N, 9.93; S,
11.35%]; nmax (potassium bromide) 3499, 3331, 3265,
3211, 2953, 2836, 1729, 1693 cmꢁ1; dH (CDCl3, 300 MHz)
12.81 (1H, br s, D2O-exchangeable, NH), 7.65 (1H, br s,
D2O-exchangeable, NH), 7.05 (1H, br s, D2O-exchangeable,
NH), 3.84 (3H, s, COOMe), 2.72 (2H, m, 80-H2), 2.64 (2H, m,
50-H2), 1.73 (4H, m, 60-H2 and 70-H2); dC (CDCl3, 75 MHz)
167.2, 167.2, 159.7, 152.6, 140.9, 129.7, 128.1, 118.1,
53.7, 25.3, 24.1, 22.5, 22.4; m/z (EI) 283 (6, MH+), 282
(43, M+), 266 (9), 265 (61), 59 (6%).
4.1.4. Reactions with 1f,g. From 2.5 mmol of 1f (or 1g,
respectively) and 1.42 g (10 mmol) of DMAD, the reactions
in methanol gave after 9 h no new products.
4.1.4.1. Dimethyl 2-{3-[1,2-di(methoxycarbonyl)vinyl]-
amino-4-[1,2-di(methoxycarbonyl)vinyl]imino-4H-thieno-
[3,4-c](2H)chromen-1-yl}butenedioate (5, E,Z-mixture).
From a mixture of 4 (0.54 g, 2.5 mmol) and DMAD (3 mL,
excess) in methanol, the reaction was conducted for 9 h.
The solvent was evaporated invacuo to give a crude material,
which was kept in the freezer for few days. The resulting pre-
cipitate was crystallized from methanol to give the title com-
pound 5 (704 mg, 44%) as orange powder, mp 165–167 ꢀC
4.1.4.3. Dimethyl 7-amino-6-oxo-6H-benzo[c](2H)-
chromen-8,9-dicarboxylate (8). [Found: C, 62.02; H,
3.98; N, 4.22. C17H13NO6 requires C, 62.39; H, 3.98; N,
4.28%]; nmax (potassium bromide) 3415, 3311, 2958, 1740,
1710 cmꢁ1; dH (300 MHz, DMSO-d6) 8.30 (1H, dd,
J 8.1, 1.5 Hz, 4-H), 8.19 (2H, br s, D2O-exchangeable,
NH2), 7.60 (1H, ddd, J 9.5, 8.0, 1.5 Hz, 3-H), 7.59 (1H, dd,
J 6.9, 1.8 Hz, 1-H), 7.39 (s, 1H, 10-H), 7.37 (1H, ddd,
J 7.9, 7.2, 1.1 Hz, 2-H), 3.86 (3H, s, COOMe), 3.80 (3H, s,

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E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7129
COOMe); dC (75 MHz, DMSO-d6) 168.1, 166.6, 161.4,
152.1, 151.3, 141.1, 139.8, 132.4, 125.2, 124.9, 117.2,
117.1, 110.0, 107.4, 104.9, 53.0, 52.8; m/z (EI) 328 (19),
327 (100, M+), 238 (22), 44 (5%).
compound 14 (see below) as yellow prisms, mp 187–
189 ꢀC. Analytical HPLC of 13a using a Merck-Hitachi
chromatograph, column length 250 mm, column diameter
5 mm, flow rate 1 mL/min, on chiral stationary phases
Merck Chiraspher NT (5 mm) with heptane/THF 50:50,
70:30, and 80:20 as well as Merck Whelk-01 (5 mm)
with hexane/2-propanol 95:5, 80:20 and 70:30, gave no
separation.
4.1.4.4. Dimethyl 2-(3-amino-4-oxo-4H-thieno[3,4-
c](2H)chromen-1-yl)butenedioate (12). Reacting
9
(0.54 g, 2.5 mmol) with DMAD (4 mL, excess) in methanol
for 5 h, gave after concentration in vacuo, a crude material,
which was crystallized from methanol to afford the title com-
pound 12 (570 mg, 64%) as red prisms, mp 154–156 ꢀC.
When the same reaction was conducted with the same inputs
of starting materials in dioxane for 8 h, compound 12 sepa-
rated from the reaction concentrate on ice-cooling (freezer),
to give the title compound 12 (159 mg, 21%) as red prisms,
mp 155–157 ꢀC (from ethanol). [Found: C, 56.73; H, 3.68;
N, 3.88; S, 8.93. C17H13NO6S requires C, 56.82; H, 3.62;
N, 3.90; S, 8.91%]; nmax (potassium bromide) 3438, 3331,
2956, 1722, 1704, 1617, 1584, 1482, 1384, 1264, 1129,
943, 888, 793 cmꢁ1; dH (300 MHz, DMSO-d6) 7.98 (2H,
br s, D2O-exchangeable, NH2), 7.38 (1H, dd, J 8.03,
1.69 Hz, 60-H), 7.37 (1H, ddd, J 7.2, 6.4, 1.7 Hz, 70-H),
7.25 (1H, dd, J 8.6, 1.3 Hz, 90-H), 7.16 (1H, ddd, J 8.2,
6.9, 1.5 Hz, 80-H), 7.16 (1H, s, 3-H), 3.68 (3H, s,
COOMe), 3.56 (3H, s, COOMe); dC (75 MHz, DMSO-d6)
166.3, 165.5, 158.8, 151.4, 136.1, 133.2, 129.7, 128.7,
124.5, 124.4, 118.1, 117.5, 105.1, 98.8, 53.5, 52.3; m/z
(EI) 361 (7, MH+2), 359 (33, M+), 301 (14), 300 (60), 299
(100), 285 (8), 268 (20), 257 (12), 242 (14), 241 (81), 240
(13), 186 (19), 59 (9), 44 (5%). On further cooling of the
mother liquor in liquid nitrogen a precipitate was collected
and crystallized from methanol to afford compound 8 (see
above, 354 mg, 44%).
Crystal structure analysis of 13a: The crystallographic data
(excluding structure factors) have been deposited at the
Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 602732. Details will be pub-
lished separately.
4.2. Acylations of 13a
4.2.1. Reaction with acetic acid anhydride.
4.2.1.1. Dimethyl 2-(3-acetamino-4-oxo-4H-benzo[f]-
thieno[3,4-c](2H)chromen-1-yl)fumarate (13b). A mixture
of 13a (52 mg, 0.13 mmol) and acetic acid anhydride (3 mL)
was treated with pyridine (4 mL) for 48 h at room tempera-
ture. Evaporation of the solvent in vacuo gave a crude mate-
rial, which was crystallized from ethyl acetate to afford the
title compound 13b (56 mg, 98%) as yellow powder, mp
241–243 ꢀC [Found: C, 60.98; H, 3.85; N, 3.10; S, 7.33.
C23H17NO7S requires C, 61.20; H, 3.77; N, 3.10; S,
7.10%]; nmax (potassium bromide) 3436, 3267, 2953, 1723,
1708, 1682 cmꢁ1; dH (500 MHz, DMSO-d6) 11.03 (1H, br
s, D2O-exchangeable, NH), 8.10 (1H, dd, J 7.4, 1.5 Hz,
110-H), 7.86 (1H, d, J 8.7 Hz, 60-H), 7.83 (1H, dd, J 7.3,
2.2 Hz, 80-H), 7.46 (2H, br ddd, J 9.8, 7.7, 1.0 Hz, 90-H and
100-H), 7.43 (1H, d, J 8.8 Hz, 70-H), 6.97 (1H, s, 3-H), 3.52
(3H, s, COOMe), 3.36 (3H, s, COOMe), 2.41 (3H, s, COMe);
dC (125 MHz, DMSO-d6) 167.7, 165.0, 164.9, 160.2, 151.1,
149.5, 137.9, 130.9, 130.8, 130.3, 128.7, 128.4, 128.1, 126.6,
126.1, 125.6, 117.8, 117.2, 112.9, 108.8, 52.8, 52.0, 23.4; m/z
(EI) 452 (4), 451 (17, M+), 421 (3), 420 (8), 419 (27), 409
(14), 378 (5), 377 (17), 393 (40), 391(86), 352 (6), 349
(100), 290 (17), 44 (6%).
4.1.4.5. Dimethyl 2-(3-amino-4-oxo-4H-benzo[f]-
thieno[3,4-c](2H)chromen-1-yl)fumarate (13a). On react-
ing 10 (0.814 g, 3 mmol) with DMAD (5 mL, excess) in
methanol for 10 h, a precipitate was obtained from the reac-
tion concentrate after ice-cooling (freezer) for several days.
Recrystallization from methanol gave the title compound
13a (777 mg, 62%) as red prisms, mp 171–173 ꢀC. When
the same quantities of 10 and DMAD were reacted for
8 hours in dioxane, compound 13a crystallized on cooling
(upon storage in a freezer) the reaction concentrate after
a few days. This crop was crystallited from ethanol to give
108 mg (26%) of red prisms, mp 174–176 ꢀC [Found: C,
61.43; H, 3.75; N, 3.34; S, 7.84. C21H15NO6S requires C,
61.61; H, 3.67; N, 3.42; S, 7.82%]; nmax (potassium bro-
mide) 3440, 3334, 3055, 2939, 1723, 1705, 1592, 1427,
4.2.2. Reaction with trifluoroacetanhydride.
4.2.2.1. Dimethyl 2-(3-trifluoroacetylamino-4-oxo-4H-
benzo[f]thieno[3,4-c](2H)chromen-1-yl)fumarate (13c).
A stirred mixture of 13a (52 mg, 0.13 mmol) and trifluoro-
acetic acid anhydride (3 mL) was heated to reflux for 24 h.
After evaporating the solvent to dryness in vacuo, the result-
ing crude material was purified by plc (hexane/ethyl acetate
7:3) and crystallized from ethyl acetate to yield the title com-
pound 13c (52 mg, 83%) as yellow powder, mp 154–156 ꢀC
[Found: C, 54.50; H, 2.70; N, 2.76; S, 6.41. C23H14NO7SF3
requires C, 54.65; H, 2.77; N, 2.77; S, 6.34%]; nmax (potas-
sium bromide) 3438, 1727, 1700 cmꢁ1; dH (500 MHz,
CDCl3) 11.91 (1H, br s, D2O-exchangeable, NHCOCF3),
8.05 (1H, dd, J 9.2, 1.0 Hz, 110-H), 7.91 (1H, d, J 8.8 Hz,
60-H), 7.86 (1H, dd, J 8.8, 1.2 Hz, 80-H), 7.49 (2H, br ddd,
J 8.4, 7.0, 1.3 Hz, 90-H and 100-H), 7.47 (1H, d, J 8.9 Hz,
70-H), 7.04 (1H, s, 3-H), 3.52 (3H, s, COOMe), 3.41 (3H, s,
COOMe); dC (125 MHz, CDCl3) 165.0, 164.8, 160.0,
149.9, 147.6, 137.5, 131.6, 131.2, 131.2, 129.7, 128.7,
128.5, 127.1, 126.3, 126.1, 120.5, 117.4, 112.7, 112.0,
53.3, 52.3; m/z (EI) 505 (6, M+), 473 (11), 447(10), 446
(31), 445 (100), 387(30), 377 (17), 393 (40), 69 (6), 59 (4%).
1332, 1263, 1113, 1079, 942, 874, 792 cmꢁ1
; dH
(300 MHz, DMSO-d6) 8.20 (2H, br s, D2O-exchangeable,
NH2), 7.99 (1H, d, J 8.84 Hz, 60-H), 7.93 (1H, dd, J 7.5,
1.9 Hz, 110-H), 7.88 (1H, dd, J 8.3, 1.4 Hz, 80-H), 7.46
(2H, br ddd, J 9.6, 6.9, 2.1 Hz, 90-H and 100-H), 7.43 (1H,
dd, J 8.8, 1.3 Hz, 70-H), 6.61 (1H, s, 3-H), 3.38 (3H, s,
COOMe), 3.26 (3H, s, COOMe); dC (75 MHz, DMSO-d6)
167.2, 165.4, 164.9, 158.7, 150.3, 137.0, 132.4, 131.0,
130.6, 128.4, 128.1, 126.7, 126.5, 125.8, 125.4, 117.2,
112.6, 106.6, 101.1, 52.9, 51.6; m/z (EI) 409 (14, M+), 377
(17), 351 (15), 350 (53), 349 (100), 335 (11), 318 (18),
292 (19), 291 (90), 175 (18), 44 (9%). Further cooling
of the mother liquor in liquid nitrogen and crystallization
of the precipitate from ethanol gave 220 mg (58%) of

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E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7130
4.2.3. Attempted reaction of 2-amino-4-(dicyanomethyl-
ene)-4H-indeno[2,3-b]thiophen-1-carbonitrile (17) with
DMAD in methanol, ethanol or dioxane. Stirred mixtures
of compound 17 (0.28 g, 1 mmol) and DMAD (3 mL) were
successively heated to reflux in methanol, ethanol and diox-
ane for 9 h. Concentration in vacuo and subsequent crystal-
lization of the resulting precipitates from dioxane gave deep
blue powders (mp>350 ꢀC), which were identified to be the
starting material 17.
the title compound 24 (550 mg, 73%) as yellow powder, mp
302–304 ꢀC [Found: C, 59.67; H, 3.72; N, 4.68; S, 10.67.
C15H11NO4S requires C, 59.80; H, 3.65; N, 4.65; S,
10.63%]; nmax (potassium bromide) 3387, 3281, 1717,
1696 cmꢁ1; dH (300 MHz, DMSO-d6) 8.37 (2H, br s, D2O-
exchangeable, NH2), 8.21 (1H, dd, J 15.0, 3.3 Hz, 2-H),
7.91 (1H, d, J 8.1 Hz, 60-H), 7.48 (1H, dd, J 7.9, 7.6 Hz,
70-H), 7.36 (1H, d, J 7.9 Hz, 90-H), 7.29 (1H, dd, J 8.2,
7.7 Hz, 80-H), 5.87 (1H, dd, J 15.0, 3.1 Hz, 3-H), 3.72 (3H,
s, OMe); dC (75 MHz, DMSO-d6) 166.4, 166.1, 158.3,
151.9, 135.4, 133.0, 130.4, 125.4, 124.8, 117.8, 117.6,
113.4, 111.6, 100.4, 51.2; m/z (EI) 303 (8), 302 (21), 301
(100, M+), 270 (32), 243 (22), 242 (96), 241 (87%).
4.2.3.1. Dimethyl 7-(acetylamino)-5-oxobenz[c](2H)-
chromen-8,9-dicarboxylate (19). From a mixture of com-
pound 18 (0.26 g, 1 mmol) and DMAD (3 mL) in dioxane,
the reaction was carried out for 8.5 h. On cooling, the pre-
cipitate was crystallized from ethanol to afford the title
compound 19 (155 mg, 42%) as yellow needles, mp 204–
206 ꢀC [Found: C, 61.61; H, 4.15; N, 3.72. C19H15NO7
requires C, 61.79; H, 4.07; N, 3.79%]; nmax (potassium
4.2.3.4. Dimethyl 3,30-[3-(4-oxo-4H-benzo[f]thieno-
[3,4-c](2H)chromenyl)]aminodipropoate (E,Z-mixture)
(26). The reaction in dioxane of a mixture of 10 (0.67 g,
2.5 mmol) with methyl propiolate (3 mL) gave after 7 h re-
fluxing no new product. The starting compound was instead
recovered after the usual work-up. From a mixture of 10
(0.54 g, 2 mmol) and methyl propiolate (3 mL) in toluene,
the reaction was carried out for 8 h. Cooling to room temper-
ature and subsequent crystallization of the solid from 10%
aqueous DMF afforded the title compound 26 (617 mg,
70%) as yellow powder, mp 291–293 ꢀC [Found: C, 63.45;
H, 3.91; N, 3.22; S, 7.36. C23H17NO6S requires C, 63.44;
H, 3.94; N, 3.22; S, 7.36%]; nmax (potassium bromide)
3445, 3061, 2957, 1727, 1661 cmꢁ1; dH (300 MHz,
DMSO-d6) 8.97 (1H, s, 100-H), 8.88 (1H, d, J 8.31 Hz, 600-
H), 8.20 (2H, d, J 13.5 Hz, 3-H and 30-H), 8.09 (2H, br d,
800-H and 1100-H); 7.82 (1H, ddd, 1000-H, J 8.5, 6.9,
1.4 Hz), 7.65 (1H, dd, J 8.7, 7.2, 7.1 Hz, 900-H), 7.53 (1H,
d, J 8.9 Hz, 700-H), 4.84 (2H, d, J 13.5 Hz, 2-H and 20-H),
3.59 (6H, s, 2ꢂCOOMe); dC (75 MHz, DMSO-d6) 166.4,
153.7, 149.9, 148.6, 143.8, 133.1, 131.1, 130.8, 129.3,
128.9, 128.6, 125.5, 124.1, 121.8, 121.6, 117.4, 110.5,
98.7, 50.7; m/z (EI) 437 (9), 436 (27), 435 (100, M+), 404
(11), 403 (12), 376 (27), 44 (7%).
bromide) 3431, 3273, 3066, 2953, 1740, 1725, 1671 cmꢁ1
;
dH (300 MHz, DMSO-d6) 10.50 (1H, br s, D2O-exchange-
able, NH), 8.55 (1H, s, 10-H), 8.43 (1H, dd, J 8.6, 1.4 Hz,
4-H), 7.63 (1H, ddd, J 8.0, 7.5, 1.3 Hz, 3-H), 7.44 (1H, dd,
J 8.1, 1.2 Hz, 1-H), 7.31 (1H, ddd, J 7.4, 7.3, 1.2 Hz, 2-H),
3.90 (3H, s, OMe), 3.75 (3H, s, OMe), 2.09 (3H, s, COMe);
dC (75 MHz, DMSO-d6) 169.4, 158.6, 166.3, 158.5, 151.0,
138.6, 137.5, 132.3, 129.1, 125.3, 125.0, 124.7, 117.3,
119.6, 117.1, 116.7, 108.5, 53.4, 52.7, 23.6; m/z (EI) 369
(26, M+), 338 (18), 327 (100), 311 (16), 310 (80), 43 (13%).
4.2.3.2. Dimethyl 4-amino-5-oxo-5H-dibenzo[c,f]-
(2H)chromen-2,3-dicarboxylate (14). From a mixture of
compound 21 (0.31 g, 1 mmol) and DMAD (3 mL) in diox-
ane, the reaction was conducted for 8.5 h. Cooling to room
temperature and subsequent crystallization of the resulting
solid material from benzene afforded yellow crystals
(160 mg), mp 284–286 ꢀC, identified in all respects to the
starting compound 21. The resulting mother liquor was
diluted with acetone and separated by plc using hexane/
ethyl acetate 3:2 to afford the unreacted excess of DMAD
and a brown amorphous substance, which was crystallized
from ethanol to give 43 mg (11%) of yellow prisms
(mp 180–182 ꢀC), identified in all respects to the title com-
pound 14, mp 183–185 ꢀC from ethanol [Found: C, 66.65;
H, 4.02; N, 3.69. C21H15NO6 requires C, 66.84; H, 3.98;
N, 3.71%]; nmax (potassium bromide): 3443, 3339, 2953,
1735, 1709 cmꢁ1; dH (500 MHz, DMSO-d6) 8.58 (1H, d,
J 8.59 Hz, 12-H), 8.16 (1H, dd, J 8.8 Hz, 7-H), 8.11 (2H,
br s, D2O-exchangeable, NH2), 8.09 (1H, br dd, J 8.1,
1.2 Hz, 9-H), 7.74 (1H, ddd, J 8.6, 7.1, 1.5 Hz, 11-H), 7.76
(1H, d, J 0.5 Hz, 1-H), 7.62 (1H, ddd, J 7.9, 7.0, 0.9 Hz,
10-H), 7.52 (1H, d, J 8.83 Hz, 8-H), 3.85 (3H, s, COOMe),
3.82 (3H, s, COOMe); dC (125 MHz, DMSO-d6) 167.7,
166.5, 160.9, 151.3, 150.6, 139.6, 139.6, 133.5, 131.3,
129.6, 128.7, 128.4, 125.8, 124.4, 116.8, 111.8, 111.5,
110.2, 105.8, 53.1, 52.7; m/z (EI) 378 (24), 377 (100, M+),
346 (24), 288 (12).
4.2.3.5. (E or Z) Methyl 3-[1-(3-amino-4-oxo-4H-
benzo[f]thieno[3,4-c](2H)chromenyl)]propenoate (27).
From a mixture of 10 (401 g, 1.5 mmol) and methyl propio-
late (3 mL) in methanol, the reaction was conducted for 7 h.
Cooling at room temperature followed by crystallization of
the precipitate from ethyl acetate gave the title compound
27 (35 mg, 7%) as yellow powder, mp 312–314 ꢀC. The
compound was not soluble enough in DMSO-d6 to afford
exploitable information from the NMR experiments. nmax
(potassium bromide) 3406, 3289, 2957, 1710, 1681 cmꢁ1
;
m/z (EI) 351 (49, M+), 320 (6), 318 (4), 297 (7), 293 (21),
292 (100), 291 (36), 290 (3%).
4.2.3.6. Dimethyl 1-phenylnaphthalene-2,3-dicarb-
oxylate (ethyl phenylethynecarboxylate dimer00) (28).
The reaction in methanol of a mixture of 10 (401 mg,
1.5 mmol) and ethyl phenylethynecarboxylate (3 mL) was
successively conducted for 54 and 48 h, respectively, in
methanol and toluene and gave no new product, but rather
the starting material 10. From a mixture of 10 (270 mg,
1 mmol) and ethyl phenylpropiolate (2 mL) in DMF, the
reaction was carried out for 7 h. The reaction mixture was
then concentrated in vacuo to half of its volume. The result-
ing precipitate was crystallized from 10% aqueous DMF to
4.2.3.3. (E,Z) Methyl 3-[1-(3-amino-4-oxo-4H-thieno-
[3,4-c](2H)chromenyl]propoate (24). From 9 (0.54 g,
2.5 mmol) and methyl propiolate (3 mL) in dioxane, the re-
action was carried out for 5.5 h. Concentration in vacuo of
the resulting solution to half of its volume gave a precipitate,
which was crystallized from dioxane/ethyl acetate to afford

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E. Sopbue Fondjo et al. / Tetrahedron 62 (2006) 7121–7131
7131
´
2. Nyiondi-Bonguen, E.; Sopbue Fondjo, E.; Tanee Fomum, Z.;
afford the title compound 28 (103 mg, 30%) as green-
yellowish powder, mp 124–126 ꢀC (lit.,16–18 127–128 ꢀC
from petroleum ether). The mother liquor was discarded;
nmax (potassium bromide) 3064, 2977, 2929, 2903, 1715,
1661 cmꢁ1; dH (300 MHz, CDCl3) 8.60 (1H, s, 7-H),
8.01–7.26 (9H, m, aromatic H), 4.42 (2H, q, J 7.1 Hz,
OCH2), 4.06 (2H, q, OCH2, J 7.2 Hz), 1.42 (3H, t, J
7.1 Hz, OCH2CH3), 0.97 (3H, t, OCH2CH3, J 7.1 Hz); dC
(75 MHz, CDCl3) 168.8, 166.0, 138.6, 136.8, 134.1, 132.4,
131.4, 131.3, 130.4, 129.3, 128.9, 128.0, 127.4, 127.0,
61.6, 61.1, 14.3, 13.7; m/z (EI) 348 (97, M+), 320 (6), 304
(9), 290 (4), 277 (3), 276 (24), 275 (100, M–COOEt), 274 (4).
Dopp, D. J. Heterocycl. Chem. 1996, 33, 281.
`
¨
3. (a) Sopbue Fondjo, E. Doctorat de3eme Cycle thesis, University
´
of Yaounde I, 1993; (b) Sopbue-Fondjo, E. Dissertation,
´
´
Gerhard-Mercaptor-Universitat Duisburg, 2000.
¨
4. Al-Omran, F.; Khalik, M. M. A.; Al-Awadhi, H.; Elnagdi,
M. H. Tetrahedron 1996, 52, 11915.
5. Flemming, I. Grenzorbitale und Reaktionen organischer
Verbindungen; VCH: Weinheim, Germany, 1990; pp 154–172.
6. Lert, P. W.; Trindle, C. J. Am. Chem. Soc. 1971, 93, 6392.
7. Gewald, K.; Schinke, E.; Bottcher, H. Chem. Ber. 1996, 99, 94;
¨
Chem. Abstr. 1966, 64, 8118.
8. Gewald, K. Angew. Chem. 1961, 73, 114; Chem. Abstr. 1961,
55, 12383.
9. Gewald, K. Z.Chem. 1962, 2, 305; Chem. Abstr. 1963, 58, 6770.
10. Gewald, K. Chem. Ber. 1965, 98, 3571; Chem. Abstr. 1966,
64, 3451.
11. Gewald, K.; Schinke, E. Chem. Ber. 1966, 99, 2712; Chem.
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Acknowledgements
The authors are grateful to the Deutscher Akademischer
´
Austauschdienst (DAAD) for granting Dr. E. Sopbue
Fondjo a Ph-D fellowship (Grant No. A/96/11507). Thanks
are due to the administration of Gerhard-Mercaptor-Univer-
sitat Duisburg for financial and technical assistance. E.S.F.
¨
also thanks very sincerely, through the Rector of the Univer-
sity of Dschang, the Ministry of higher education of the
Republic of Cameroon for granting a leave to the above
mentioned author, for the implementation of this work.
Generous donation of chemicals by Fonds der Chemischen
Industry is gratefully acknowledged.
13. Manhas, M. S.; Rao, V. V.; Seetheraman, P. A.; Succardi, D.;
Pazdera, J. J. Chem. Soc. C 1969, 1937.
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1972, 9, 775.
15. (a) Ried, W.; Nyiondi-Bonguen, E. Liebigs Ann. Chem. 1973,
1, 134; (b) Nyiondi-Bonguen, E. Dissertation, Univ. Frankfurt/
Main, 1972.
16. Pfeiffer, P.; Moller, W. Chem. Ber. 1907, 40, 3841.
¨
References and notes
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¨