Condensation of some ketones with methylene active nitriles in varied stoichiometries

Article abstract of DOI:10.1002/jhet.5570430433

Condensations of some ketones, such as cyclopentanone, cyclohexanone, indan-1,3-dione, 2-acetyl-1-naphthol, 1-acetyl-2-naphthol, with some active methylene compounds, such as malononitrile and cyanoacetate, in the presence of amine bases, diethylamine or triethylamine, were studied. The structures of the Knoevenagel condensation products were determined by pectral analyses.

Full text of DOI:10.1002/jhet.5570430433

Jul-Aug 2006
Condensation of Some Ketones with Methylene
Active Nitriles in Varied Stoichiometries
Emmanuel Sopbué Fondjoa)* and Dietrich Döppb)
1037
a) Laboratory of Applied Synthetic Organic Chemistry, Department of Chemistry, Faculty of Science,
University of Dschang, PO Box 067, Dschang, Republic of Cameroon
E-mail: sopbue@yahoo.fr .
b)Organische Chemie, Universität Duisburg-Essen, D-47057 Duisburg, Germany
E-mail: dietrich.doepp@uni-duisburg-essen.de
Received November 4, 2005
(CH2)n
NC
-
R
CN
CN
O
4
3
HN
3a
H2C(CN)2/MeOH
5
(CH2)n
+
H2C(CN)2/MeOH
NC
(CH2)n
2
HN(Et)3
6
N(Et)3/ꢀ
7a
1
H2N
7
HN(Et)2/ꢀ
O
CN
O
NC
n = 1, R = CH(CN)2
n = 2, R = OMe
NH2
NH2
1
2
11
12
14
1
3
14a
CN
NH2
11
O
H3C
O
13
10
9
2
12b
12
CN
12a
8a
H2C(CN)2
ꢀ/MeOH
4
/HN(Et)2
12c
10
4a
11a
OH
4a
3
12a
N
NH2
+
12b 4b
8
7
O
4
5
5
6a
7a
9
NH
8
N
6a
6
O
NH
7
H
Dedicated to Professor M. Tiꢀsler at the occasion of his 80th birthday.
Condensations of some ketones, such as cyclopentanone, cyclohexanone, indan-1,3-dione, 2-acetyl-1-
naphthol, 1-acetyl-2-naphthol, with some active methylene compounds, such as malononitrile and
cyanoacetate, in the presence of amine bases, diethylamine or triethylamine, were studied. The structures
of the Knoevenagel condensation products were determined by spectral analyses.
J. Heterocyclic Chem., 43, 1037 (2006).
Introduction.
ppm (3a-H), 4.09-4.12 ppm (olefinic 1-H), 5.47 ppm
(CH(CN)2), and also showed two broad singlets,
exchangeable with D2O, around 6.70 and 9.46 ppm (NH2 and
N=H). The 13C NMR (DMSO-d6) showed resonances
corresponding to six methylene carbon atoms, three tertiary
carbon atoms, and ten quaternary carbon atoms.
The Knoevenagel condensation reaction [1-3] of
ketones with methylene active nitriles (malononitrile,
alkyl cyanoacetate, etc.) is the key step in the synthesis of
2-aminothiophene derivatives through both variants of the
Gewald method [4-13]. We here report the results of
various attempts to prepare the intermediates in both one
and two-pot procedures of the Gewald synthesis, from
cyclopentanone, cyclohexanone, indan-1,3-dione, 1-acetyl-
2-naphthol and 2-acetyl-1-naphthol and methylene active
nitriles (malononitrile, methyl and ethyl cyanoacetate) in
the presence of bases (diethylamine and triethylamine).
Scheme 1
CN
CN
NC
2a, Et2NH
CN
HN
NC
O
H2N
MeOH
3a
1a
CN
Results and Discussion.
CN
CN
MeO
The condensation of cyclopentanone (1a) with malono-
nitrile (2a) in refluxing methanol in the presence of
diethylamine gave the bicyclic compound (3a) as colorless
needles, mp 274-276 °C instead of the anticipated compound
5a. The IR spectrum of 3a showed NH bands at 3443, 3327,
3284, and 3237 cm-1 and the nitrile band at 2212 cm-1. The
mass spectrum of 3a showed the molecular ion peak at m/z
330 (100%), corresponding to the molecular formula
2a
, Et2NH
HN
NC
O
MeOH
H2N
1b
4b
CN
Condensation of Cyclopentanone (1a) or Cyclohexanone (1b) with
malononitrile (2a).
1
C19H18N6. The H NMR spectrum (DMSO-d6) showed the
multiplets signals at 1.53-2.91 ppm (six methylenes), 3.16
The analogous condensation of cyclohexanone (1b) with
malononitrile (2a) under the same reaction conditions also

1038
E. Sopbué Fondjo and D. Döpp
Vol 43
gave a bicyclic compound (4b) [14-17] as colorless needles,
mp 216-218 °C instead of the anticipated compound 5b. The
IR spectrum of 4b showed NH bands at 3423, 3327, and
3217 cm-1 and nitrile bands at 2240 and 2207 cm-1.
carbon atom, eight methylene carbon atoms, two tertiary
carbon atoms, and eight quaternary carbon atoms.
Scheme 3
Scheme 2
NC
NC
CN
CN
CN
O
O
2a
CN , Et3N
(CH2)n
CN
Et3NH
CN
NC
NC
MeOH
CN
CN
2a
CN
(CH2)n
O
(CH2)n
1a,b
(CH2)n
8c
CN
Et2NH
NC
NC
N
C
5a,b
1c
5c
Condensation of indan-1,3-dione (1c) with malononitrile (2a).
CN
(CH2)n
(CH2)n
The formation of the product 5c might be explained by
double Knoevenagel condensation of 1c with 2 moles of
malononitrile 2a followed by deprotonation with
triethylamine.
NC
NC
NC
(CH2)n
(CH2)n
NC
HN
H2N
CN
CN
6a,b
7a,b
CN
In refluxing methanol 2-acetyl-1-naphthol (1d) and 1-
acetyl-2-naphthol (1e) react with cyanoacetic esters 2b,c
in the presence of diethylamine to yield the known
[20,21] benzocoumarins 5d,e (Scheme 4).
The condensation of 2-acetyl-1-naphthol (1d) with
malononitrile in the presence of diethylamine and sulfur
in a one pot-procedure [4-13], did not give as expected the
condensed 2-aminothiophene 11d, but instead the mixture
of compounds 9d and 10d (Schemes 5 and 6).
Et2NH
2a
CN
3a
Mechanism for 3a and 4b.
Et2NH
MeOH
4b
The mass spectrum of 4b revealed the molecular ion
peak at 324 (45%), corresponding to the molecular
formula C19H24N4O. The H NMR spectrum (DMSO-
1
d6) showed multiplet signals at 1.20-2.26 ppm (eight
methylenes), 3.61 ppm (8a-H), 3.70 ppm (OCH3), 5.71
ppm (olefinic 5-H), and also showed two broad singlets,
exchangeable with D2O, around 6.53 and 7.98 ppm
(NH2 and N=H). The 13C NMR (DMSO-d6) showed
resonances for one methoxy carbon atom, eight
methylene carbon atoms, two tertiary carbon atoms, and
eight quaternary carbon atoms.
Similarly the reaction of 1-acetyl-2-naphthol (1e)
with ethyl cyanoacetate in the presence of diethylamine
in a one pot-procedure [4-13] gave compound 5e
(Scheme 7) instead of the anticipated fused 2-amino-
thiophene 11e [22].
Scheme 4
Nucleophilic attacks in 6a,b might be possible on both
types of nitrile groups, but the conjugated nitrile is less
reactive than the unconjugated nitrile groups.
R1
R1
CH3
O
R2
R3
R2
CN
O
X
HNEt2
CH3
H2C
+
3
R
ꢀ/MeOH
The analogous condensation of indan-1,3-dione (1c)
with malononitrile (2a) in refluxing methanol in the
presence of triethylamine the salt 8c as deep blue
needles, mp 198-200 °C. The IR spectrum of 8c showed
the NH bands at 3429 cm-1 and the nitrile bands at 2209
and 2191 cm-1. The elemental analysis of 8c proved the
molecular formula C21H21N5 and the mass spectrum of 8c
CN
O
OH
2b,c
X = CO2CH3, CO2C2H5
R4
R4
5d,e
1d,e
1, 5 R1 R2 R3 R4
d
e
H
C4H4
H
C4H4
H
H
1
Condensation of 2-acetyl-1-naphthol (1d) and 1-acetyl-2-naphthol (1e)
with cyanoacetates (2b,c).
showed the peak at m/z 242 (M-Et3N, 79%). The H
NMR spectrum (DMSO-d6) showed the three triplet
methyl signals at 1.19 ppm (N-CH2CH3) and three
methylene signals at 3.11 ppm (N-CH2CH3), 5.52 ppm
(olefinic 2-H), 7.42 and 7.92 ppm (aromatic protons),
and also showed two broad singlets, exchangeable with
D2O, around 8.85 ppm (NH+). The 13C NMR (DMSO-d6)
showed resonances corresponding to one methoxy
The reaction of 1e with malononitrile in boiling
methanol in the presence of diethylamine did not give as
the expected compound 5e', but rather the two polycyclic
compounds 13e and 14e (Scheme 8) in 25 and 10% yields
respectively.

Jul-Aug 2006
Condensation of Some Ketones with Methylene
Active Nitriles in Varied Stoichiometries
1039
Scheme 5
CH3 NH
1d + 2a
CN
HNEt2
S
CN
O
NH
S
CH3
9d
NH2
S
CN
NH
2a
+
O
NH
O
CH3 NH2
CH3 NH2
CN
CN
NH
11d
5d'
CN
NH
O
O
N
10d
Condensation of 2-acetyl-1-naphthol (1d) with malononitrile (2a).
Scheme 6
CN
CN
OH
O
HN
O
O
2a , Et2NH
CN
CH3
CH3
5d'
MeOH
1d
12d
10d
9d
Formation of 9d and 10d.
Compound 14e was obtained as the first precipitate,
crystallizing as high melting (mp > 350 °C) yellow
powder from acetone. In the high frequencies region of
the IR spectrum the absorptions bands of the N-H-
stretchings of the =NH, -NH- and NH2-groups could be
seen at ꢀ 3452, 3353 and 3270 cm-1.
Scheme 7
S
CO2C2H5
NH2
+ S
HNEt2
S/HNEt2
EtOH
1e
H2C
+
5e
CN
O
11e
O
2c
The absorption frequencies of the nitrile and carbonyl
groups appear at ꢀ 2205 and 1636 cm-1, respectively. The
Condensation of 1-acetyl-2-naphthol (1e) with ethyl cyanoacetate (2c).
Scheme 8
CH3
CN
NH
H3C
O
O
OH
5e'
HNEt2
ꢀ/MeOH
2
1e
NH2
NH2
1
3
11
12a
14
1
O H2N
14a
+
CN
12
10
9
13
12c
12b 4b
12b
12
11
2
CN
NH
4
H2C(CN)2
10
4a
11a
12a
4a
3
+
8a
8
7
N
NH2
5
4
6a
5
7a
9
N
H
O
8
6
6a
O
NH
7
6
13e
14e
Condensation of 1-Acetyl-2-naphthol (1e) with malononitrile (2a).

1040
E. Sopbué Fondjo and D. Döpp
Vol 43
Scheme 9
CN
NH
H3C
O
H3C
O
O
CN
CN
CN
OH
O
O
2a , Et2NH
MeOH
16e
1e
15e
CN
CN
CN
NH
H3C
O
C
O
CN
CN
CN
OH
O
O
5e
CN
CN
20e
21e
CN
CN
HN
H2C
O
NH2
CN
CN
CN
NH
O
O
14e
22
17e
CN
CN
HN
H2N
H2N
NH2
NH
CN
NH2
CN
H2N
H2N
NH2
NH
N
NH
O
O
O
19e
Proposed formation of 13e and 14e.
18e
13e
mass spectrum showed the molecular ion peak at m/z 302
(100%) and characteristic fragment ion peaks at m/z 275
(6%, cleavage of HCN), m/z 274 (13%, cleavage of the
carbonyl function). The peaks at m/z 66 (7%), 44 (11%)
and 42 (7%) were respectively attributed to the fragment
ions (H2N-CC-CN)+., (CO2)+. and (HN=C=NH)+..
between ꢀ3H and the poorly resolved dd at ꢀꢁ 8.07 ppm
consisting of one proton, which was logically assigned to
4-H. Furthermore, the spectrum showed two doublets at
ꢀꢁ 8.32 ppm and ꢀꢁ 7.63 ppm, connected by a single
cross-peak. These signals should consequently be
assigned to 5-H and 6-H, respectively. The spectrum
exhibited also at ꢀH 7.79 ppm and ꢀH 7.54 ppm two broad
singlets for one and two protons, respectively assigned to
=NH (or –NH-) and –NH2. The 13C(1H)-NMR (DMSO-d6,
125 MHz) spectrum consisted of seventeen lines, amongst
which a downfield peak at ꢀC 179.83 ppm, which is an
unequivocal proof of the presence of a carbonyl group in
14e. The DEPT-135 spectrum showed the signals of six
tertiary carbon atoms. Ten other signals of quaternary
carbon atoms could be found and readily assigned.
Besides the multiplet of the naphthalene protons
between ꢀH 9.89-7.54 ppm, a D2O-exchangeable broad
1
singlet could be identified from the 500 MHz H NMR
(DMSO-d6) spectrum. The integral pattern is consistent
with the existence of ten protons. The doublet of doublets
(dd) at ꢀꢁ 9.88 ppm has a broad basis and corresponds to
1
two protons. The H,1H-COSY-45 spectrum showed only
a single cross-peak between this dd and the 1H-ddd at ꢀꢁ
7.76 ppm. The dd at 9.88 ppm that should be assigned to
1-H overlaps with the broad singlet of –NH- or =NH.
Consequently, the ddd at ꢀꢁ 7.76 ppm and ꢀꢁ 7.64 ppm
should be assigned to 2-H and 3-H. Aside from the cross-
peak between ꢀ3H and ꢀ2H, there is another cross-peak
The mother liquor of 14e was kept in the
refrigerator for several days, after which a yellow
precipitate consisting of 13e was isolated. This
compound crystallizes as yellow powder from

Jul-Aug 2006
Condensation of Some Ketones with Methylene
Active Nitriles in Varied Stoichiometries
1041
Scheme 10
CN
N
H
O
NH
N
2 NH2
NH
CN
OH
NC
O
NH2
N
CN
O
H2N
NH2
NH2
CN
N
H
O
NH
NH
O
23B
O
23A
H
24A
23C
NH2
NH2
CN
NH2
NH2
N
CN
N
H2N
H2N
NH2
NH2
NH
N
N
NH2
CN
N
O
N
CN
N
O
O
N
O
NH2
NH2
H
24C
24D
24E
24B
CN
H2N
H2N
NH2
NH2
NH
CH2
O
N
CN
NH
NH2
N
CH3
O
CH3 N
N
CN
CN
OH
CN
NH2
N
N
NH2
N
NH
O
NH2
H2N
24F
24G
24H
24I
Other possible isomers of 13e and 14e.
acetone and has a sharp melting point at 328 °C. In
the IR spectrum, the absorption bands of the amino-
and imino-groups are observed at ꢀ 3458, 3347 and
3231 cm-1, whereas the absorption of the nitrile
group appeared at ꢀ 2204 cm-1. The mass spectrum
exhibited the molecular ion peak at m/z 366 (75%)
and the base peak at m/z 349 (100%). The latter is
certainly due to the elimination of an NH3 molecule
from the molecular ion.
The 1H NMR (DMSO-d6, 300 MHz) spectrum
contained signals in the range 10.03-5.71 ppm, the
integrals of which represent a total of fourteen
protons. The most down field 1H-broad singlet at ꢁꢂ
10.03 ppm, which disappeared after treatment with
D2O, was assigned to =NH. Similarly, the broad
singlets at ꢁꢂ 6.65, 6.47 and 5.71 ppm, which are
equally D2O-exchangeable and represent two protons
each, were respectively attributed to the amino-groups
at C-14, C-1 and C-3. The signal of 13-H is found at
ꢁH 6.23 ppm as a sharp singlet integrating for one
proton. Moreover, the characteristic splitting of the
AB-(7-H and 8-H) and ABCD-(9-H to 12-H) systems
belonging to the naphthalene ring could be identified
in the aromatic region between 7.96-7.12 ppm. The
exact assignments of these protons were achieved with
the help of the following experiments [23]:
NOE-difference Spectroscopy.
Irradiation of the signal at ꢁH 6.23 ppm (sole singlet in
the ArH-region and attributed to 13-H) resulted in the
enhancement of the signals at ꢁH 6.65 ppm (14-NH2) and
ꢁH 7.13 ppm (12-H). Irradiation at ꢁH 7.13 ppm (12-H)
induced an effect on the signal of the directly opposite
"bay"-proton 13-H. Another resulting intensity enhance-
ment is observed at ꢁH 7.88 ppm (assigned 11-H).
Because of the poor resolution of the multiplet at ꢁH 7.31-
7.40 ppm (for 11-H, 10-H and 7-H), an accurate
irradiation is uncertain. One could nevertheless recognize
the interactions with 13-H, 12-H and 9-H (ꢁH 7.88 ppm).
The irradiation into this signal intensifies the resonances
of 8-H and 10-H. Enhancements of the signals 9-H (ꢁH
7.88 ppm) and 7-H (ꢁH 7.31 ppm) were observed when 8-
H (ꢁH 7.95 ppm) was irradiated. The irradiation of 14-NH2
(ꢁH 6.65 ppm) produced an effect on 13-H (ꢁH 6.23 ppm);
1H-13C(1H)-COSY
1
Only the H-signals at ꢁH 7.95 (8-H), 7.88 (9-H), 7.37
(11-H), 7.33 (10-H), 7.30 (7-H), 7.13 (12-H) and 6.23
ppm (13-H) showed cross-peaks with carbon atoms.
Therefore the broad singlets at ꢁH 6.65, 6.47 and 5.71 ppm
could be attributed to NH2-groups, and that at ꢁH 10.03
ppm to =NH.

1042
E. Sopbué Fondjo and D. Döpp
Vol 43
1H, 1H-COSY.
A stirred mixture of cyclohexanone (2.45 g, 25 mmol),
malononitrile (1.65 g, 25 mmol) and diethylamine (ca. 2 ml)
dissolved in methanol (15 ml), was heated to reflux for 3 hours and
kept in the refrigerator for several days. The precipitate was
crystallized from methanol to give 4b (4.35 g, 54%) as white
powder, mp 216-218 °C (Lit. [15] 227-230- from acetone); ir
(potassium bromide): 3423, 3327, 3217 (=NH and NH2-Groups),
2942, 2847 (aliph. C-H), 2240, 2207 (CN-groups), 1647, 1597
(C=N/C=C) cm-1; 1H nmr (DMSO-d6): ꢀ 2.26-1.20 (m, 16H, 8
methylene groups), 3.61 (s, 1H, 8a-H), 3.70 (s, 3H, OCH3), 5.71 (m,
1H, 5-H), 6.53 (broad s, 2H, NH2, deuterium oxide-exchangeable),
7.98 (broad s, 1H, =NH, deuterium oxide-exchangeable); 13C(1H)
nmr (DMSO-d6): ꢀ 162.16 (C=NH), 147.55 (C-3), 129.35 (C-4),
120.66 (C-5), 118.14 (C-4a), 116.92 (CN), 82.34 (CN), 61.85 (C-2),
54.61 (OCH3), 41.95 (C-1), 41.45 (C-8a), 31.82, 27.94, 26.13,
24.91, 23.53, 23.20, 22.90, 22.42 (8 methylene groups); ms: m/z (%)
The following correlations were observed: 7-H with 8-
H, 9-H with 10-H, 10-H with 11-H, 11-H with 10-H and
12-H.
Moreover 14 signals of quaternary carbon atoms could
be easily identified from the spectrum and readily
assigned.
The failure to isolate the anticipated compound 5e',
might certainly be due to the drastic reaction conditions
(reflux), compared with the usual ones [1-3]. The
formation of compounds 13e and 14e can be rationnalized
as shown in Scheme 9. All the other possible isomeric
structures of 14e (23A-C, Scheme 10) and 13e (24A-I,
Scheme 10) were ruled out on the basis of the above
discussed spectroscopic data. Furthermore, the ferric
chloride enol test [24] carried out with compound 13e
gave no positive result, excluding therefore the presence
of a free phenolique OH group as in isomers 24A and 24I.
324 (M+., 45), 323 (M+. – 1, 7), 309 (M+. – CH3, 15), 295 (M+.
–
HC=O+, 14), 294 (M+. – H2C=O, 49), 293 (M+. – OCH3, 100), 292
(M+. – HOCH3, 49), 77 (7), 67 (H2C(CN)2 + H, 8), 60 (10), 58 (15),
+
+
55 (C4H7 , 7), 41 (C3H5 , 35).
Anal. Calcd. for C19H24N4O (324.43): C, 70.37; H, 7.41; N,
17.28. Found: C, 70.55; H, 7.45; N, 17.23.
EXPERIMENTAL
Triethylammonium-1,3-bis(dicyanomethylene)-2-indanide (8c).
A solution of triethylamine (2 ml), indan-1,3-dione (0.73 g, 5
mmol) and malononitrile (0.66 g, 10 mmol) in methanol, was
heated to reflux for 4 hours. The deep blue precipitate (720 mg),
which resulted by immediate cooling, was not further purified
for analyses. The filtrate was concentrated to half of its volume
and kept for few days in the refrigerator. The solid was
crystallized from methanol and subsequently sublimed at 150-
160-/1.8.10-2 mbar as deep blue prisms (200 mg, 12%), m.p.
198-200 °C; ir (potassium bromide): 3429 (NH), 3055 (aromatic
C-H), 2835, 2436 (aliph. C-H), 2209, 2191 (CN), 1635, 1554
(C=N/C=C) cm-1; uv/vis (ethanol): ꢁmax (log ꢂ): 247 (4.46) 390
(sh, 4.05), 367 (4.24), 510 (sh, 3.80), 546 (4.26), 584 (4.42), 633
(4.30) nm; ꢁmin (log ꢂ): 281 (3.42), 422 (2.40) nm; 1H nmr
(DMSO-d6): ꢀ 1.19 (t, 9 H, HN+(CH2CH3)3, J = 7.29 Hz), 3.11
(dq, 6H, HN+(CH2CH3)3, J = 4.81, 7.26 Hz), 5.72 (s, 1H, 2-H),
7.42 (dd, 2H, 5-H and 6-H, J = 2.39, 8.31 Hz), 7.92 (dd, 2H, 4-H
and 7-H, J = 3.91, 10.61 Hz), 8.85 (broad s: 1H, NH, deuterium
All the elemental and spectroscopic analyses were performed
in the chemistry department analytical centre of Gerhard
Mercator Universität-GH-Duisburg, Duisburg (Germany). All
the melting points were determined with a Reichert Thermovar
microscope and are uncorrected. The IR and UV spectra were
measured with Perkin-Elmer 983 and 554 spectrophotometers,
respectively. 1H and 13C(1H) NMR spectra were recorded on
WM 300 and 500 instruments, with TMS as internal standard.
Coupling constants in brackets are reported in Hertz. Mass
spectra were obtained on Varian MAT 311A and AMD 604
instruments by Electron Impact Ionisation (EI) at 70 eV, on
direct inlet system. Combustion analyses were carried out with
CHN + O/S elemental analyser "CARLO ERBA" Model 1106.
[6-Amino-5,7-dicyano3,3a,4,5-tetrahydro-(4-spirocyclopentan-
2H-inden)-5-yl]iminomethylpropanedinitrile (3a).
oxide-exchangeable); 13C(1H) nmr (DMSO-d6):
ꢀ 158.10
A stirred mixture of diethylamine (ca. 2 ml), cyclopentanone (2.1
g, 25 mmol) and malononitrile (1.65 g, 25 mmol) dissolved in
methanol (15 ml), was heated to reflux for 2 hours and kept in the
refrigerator for several days. The precipitate, was crystallized from
methanol to give 3a as colourless crystals (1.42 g, 17%), m.p. 274-
276 °C; ir (potassium bromide): 3443, 3327, 3237 (=NH- and NH2-
groups), 2963, 2878 (aliph. C-H), 2212 (CN-groups), 1648, 1596,
1532 (C=N, C=C) cm-1; 1H nmr [500 MHz; DMSO-d6]: ꢀ 2.91-2.64
and 2.46-1.53 (m, 12H, methylen groups), 3.18-3.16 (m, 1H, 3a-H),
4.12-4.09 (m, 1H, 1-H), 5.47 (s, 1H, -CH(CN)2), 6.70 (broad s, 2H,
NH2, deuterium oxide-exchangeable), 9.46 (broad s, 1H, =NH,
deuterium oxide-exchangeable); 13C(1H) nmr (DMSO-d6): ꢀ 136.36,
120.28, 117.25, 116.49, 51.03, 48.61, 48.48, 40.79, 34.19, 33.34,
31.59, 28.15, 26.81, 26.79; ms: m/z (%) 330 (M+., 100), 329 (M+.,
16), 304 (5), 303 (M+. – C2H3, 21), 302 (M+. – C2H4, 17), 301 (M+. –
C2H5, 20), 67 (H2C(CN)2 + H, 9), 41 (C3H5+, 6).
(C(CN)2), 137.82 (C-1 and C-3), 130.01 (C-4 and C-7), 121.49
(C-5 and C-6), 117.87/102.70 (CN), 117.76 (C-3a and C-7a),
50.31 (C-2), 45.77 (CH2CH3)3), 8.57 (CH2CH3)3); ms: m/z (%)
243 (14), 242 (M+. - N(CH2CH3)3, 79), 241 (3), 216 (9), 215
(46), 214 (8), 189 (7), 188 (19), 187 (4), 178 (6), 151 (4), 108
(4), 102 ((CH3CH2)3NH+., 3), 101 ((CH3CH2)3N+, 44), 100 (13),
87 ((CH3CH2)3NH+. – CH3, 12), 86 ((CH3CH2)3N+ - CH3, 100),
72 ((CH3CH2)2N+, 8), 70 (6), 58 ((CH3CH2)2N+ – CH2, 67), 57
(CH2CH3)2N+ – CH3, 3), 56 (10), 44 ((CH3)2N+, 26).
Anal. Calcd. for C21H21N5 (343.44): C, 73.47; H, 6.12; N,
20.41. Found: C, 73.16; H, 6.14; N, 20.17.
4-Methyl-2-oxo-2H-benzo[h]chromene-3-carbonitrile (5d).
To a mixture of 2-acetyl-1-naphthol (7.44 g, 0.04 mol),
methylcyanoacetate (9.90 g, 0.1 mol) or ethylcyanoacetate
(11.30 g, 0.1 mol) dissolved in methanol, diethylamine (7.30
g, 0.1 mol) was added. The solution was heated to reflux for
3 hours. The resulted precipitate was crystallized from
acetone as yellow powder 8.73 g (86%), respectively 7.90 g
Anal. Calcd. for C19H18N6 (330.40): C, 69.10; H, 5.45; N,
25.45. Found C, 68.83; H, 5.66; N, 24.57.
3-Amino-2,4-cyano-1,2,6,7,8,8a-hexahydronaphthalin-1-spiro-
cyclohexan-2-imidic acid methyl ester (4b).

Jul-Aug 2006
Condensation of Some Ketones with Methylene
Active Nitriles in Varied Stoichiometries
1043
(94%), m.p. 286-288 °C (Lit. 237-239 °C [21], 280 °C from
DMF [20]); ir (potassium bromide): 2229 (CN), 1727 (C=O
coumarin), 1630, 1601, 1585, 1551, 1501 (C=C) cm-1; uv
(ethanol): ꢀmax(log ꢁ): 282 (4.65), 272 (4.55), 239 (4.05), 317
(4.15), 331 (4.19), 378 (4.00), 396 (3.90) nm; 1H nmr
(DMSO-d6): ꢂ 2.83 (s, 3H, CH3), 7.78 (ddd, 1H, 9-H, J =
1.24, 6.56, 8.00 Hz), 7.84 (ddd, 1H, 8-H, J = 1.25, 6.50, 7.83
Hz), 7.94 (d, 1H, 5-H, J = 8.89 Hz), 7.98 (d, 1H, 6-H, J =
9.05 Hz), 8.12 (dd, 1H, 7-H, J = 1.64, 7.35 Hz), 8.42 (dd, 1H,
10-H, J = 1.06, 7.65 Hz); 13C(1H) nmr (DMSO-d6): ꢂ 164.53
(C-2), 157.10 (C-10b), 150.77 (C-3), 135.96 (C-4), 130.54
(C-8), 128.33 (C-7), 128.24 (C-9), 125.13 (C-6), 122.53 (C-
10), 121.95 (C-4a), 121.83 (C-5), 114.62 (C-10a), 114.22 (C-
6a), 100.65 (CN), 19.00 (CH3); ms: m/z (%) 236 (M+. + 1,
19), 235 (M+., 100), 208 (M+. – HCN, 9), 207 (M+. – CO, 54),
206 (M+. – HCO, 22), 76 (C6H4+., 18).
168.51 (C-2), 152.95 (C-10b), 149.02 (C-1'), 142.94 (C-3),
134.49 (C-4a), 128.65 (C-10), 127.94 (C-8), 127.24 (C-6),
123.27 (C-10a), 121.65 (C-7), 121.57 (C-9), 121.29 (C-5),
116.45 (C-4), 115.07 (C-6a), 113.80 (CN), 50.26 (CH(CN)2),
15.56 (s, 3H, CH3); ms: m/z (%) 300 (M+., 39), 299 (M+. – 1,
18), 272 (M+. – 28, 4), 271 (6), 235 (M+. - CH(CN)2, 18), 234
(M+. – H2C(CN)2, 100), 233 (3), 208 (M+. - HN=C-CH(CN)2, 8),
207 (M+. – HN=CH-CH(CN)2, 53), 76 (10), 75 (4), 66
(H2C(CN)2, 52), 65 ((CN)2CH+., 5), 64 ((CN)2C+., 3), 63 (7), 44
+.
(O=C=NH2 , 8).
Anal. Calcd. for C18H12N4O (300.33) : C, 72.00; H, 4.00; N,
18.67. Found: C, 71.54; H, 3.88; N, 18.56.
2-[Amino-4-methyl-2H-benzo[h]chromen-3-yl)-methylene]-malo-
nonitrile or 8-Amino-10-imino-7-methyl-10H-12-oxa-11aza-
benzo[a]anthracene-9-carbonitrile (10d).
Anal. Calcd. for C15H9NO2 (235.25): C, 76.60; H, 3.83; N,
5.96. Found: C, 76.37; H, 3.97; N, 6.06.
From the filtrate of the above recrystallization, a solid
material was collected, consisting of 10d as yellow powder (848
mg, 29%), m.p. 288-290 °C; ir (potassium bromide): 3415,
3324, 3222 (=NH and NH2-groups), 2993 (aromatic and
aliphatic C-H), 2223, 2207 (CN groups), 1654 (C=N), 1622,
1592, 1566, 1527 (C=C) cm-1; ms: m/z (%) 300 (M+., 100), 299
(M+. – 1, 47), 298 (3), 284 (M+. – NH2, 4), 274 (M+. – CN, 4),
273 (M+. – HCN, 4), 272 (M+. – 28, 11), 271 (14), 257 (4), 254
(3), 246 (3), 245 (4), 244 (3), 235 (M+. – CH(CN)2, 15), 234 (M+.
– H2C(CN)2, 75), 233 (5), 229 (4), 228 (3), 208 (M+. – HN=C-
CH(CN)2, 6), 207 (M+. – HN=CH-CH(CN)2, 39), 76 (9), 75 (4),
67 (3), 66 (H2C(CN)2+., 36), 65 ((CN)2CH+, 4).
1-Methyl-3-oxo-3H-benzo[f]chromene-2-carbonitrile (5e).
To a mixture of 1-acetyl-2-naphthol (3.72 g, 0.2 mol),
methylcyanoacetate (9.90 g, 0.1 mol) or ethylcyanoacetate
(11.30 g, 0.1 mol) dissolved in methanol, diethylamine
(7.30 g, 0.1 mol) was added. The solution was heated to
reflux for 3 hours. The precipitate was crystallized from
acetone as yellow powder (3.50 g, 74%) respectively (1.2 g,
26%), m.p. 240 °C (Lit. [21] > 148 °C); ir (potassium
bromide): 2222 (CN), 1729 (C=O coumarin), 1619, 1600,
1
1581, 1535, 1513 (C=C/C-O) cm-1; H nmr (DMSO-d6): ꢂ
Reaction of 2-Hydroxy-1-acetonaphthone (1e) with
Malononitrile.
3.16 (s, 3H, CH3), 7.61 (d, 1H, 5-H, J = 8.98 Hz), 7.69
(ddd, 1H, 8-H, J = 1.00, 6.96, 7.95 Hz), 7.79 (ddd, 1H, 9-H,
J = 1.65, 6.99, 8.67 Hz), 8.13 (dd, 1H, 7-H, J = 0.8, 8.67
Hz), 8.38 (d, 1H, 6-H, J = 9.01 Hz), 8.64 (dd, 1H, 10-H, J =
1.44, 8.00 Hz); 13C(1H) nmr (DMSO-d6): ꢂ 164.66 (C-3),
156.86 (C-4a), 154.98 (C-2), 137.84 (C-6), 131.31 (C-1),
130.16 (C-7), 129.35 (C-9), 126.54 (C-8), 125.79 (C-10),
117.42 (C-5), 115.02 (C-10b), 113.52 (C-10a), 113.52 (C-
6a), 101.72 (CN), 25.17 (CH3); ms: m/z (%) 236 (M+. + 1,
17), 235 (M+., 100), 234 (M+. – H, 11), 208 (M+. – HCN, 6),
A stirred mixture of 1e (1.86 g, 10 mmol), malononitrile (1.32
g, 20 mmol) and diethylamine (1.46 g, 20 mmol) in methanol
was heated to reflux for 2 hours. The precipitate was crystallized
from acetone to give compound 14e (364 mg, 10%) as yellow
powder, mp > 350 °C The filtrate was kept for few days in
the refrigerator to give another precipitate, which was also
crystallized from acetone to afford compound 13e (766 mg,
25%) as yellow powder, m.p. 326-328 °C.
207 (M+. –CO, 37), 206 (M+. – HCO, 40), 190 (M+.
–
11-Amino-9-imino-12-oxo-8,9-dihydro-12H-benzo[f](4H)chro-
meno[2,3-b]pyridin-10-carbonitrile (14e).
.
HCO2 , 9), 76 (C6H4+., 20), 75 (7).
Anal. Calcd. for C15H9NO2 (235.25): C, 76.60; H, 3.83; N,
5.96. Found: C, 76.02; H, 3.98; N, 6.00.
Ir (potassium bromide): 3452, 3353, 3270 (=NH, -NH- and
NH2-groups), 2205 (CN), 1636 (C=O), 1606, 1573, 1543, 1515
2-[Imino-(2-imino-4-methyl-2H-benzo[h]chromen-3-yl)-methyl]
malononitrile (9d).
1
(C=C, C=N) cm-1; H nmr (DMSO-d6): ꢂ 7.54 (broad s, 2H,
NH2, deuterium oxide-exchangeable), 7.62 (d, 1H, 5-H, J = 9.05
Hz), 7.64 (ddd, 1H, 3-H, J = 1.20, 6.89, 8.09 Hz), 7.76 (ddd, 1H,
2-H, J = 1.49, 7.06, 8.63 Hz), 7.79 (broad s, 1H, -NH-/=NH,
deuterium oxide-exchangeable), 8.07 (d, 1H, 4-H, J = 7.24 Hz),
8.32 (d, 1H, 6-H, J = 8.82 Hz), 9.88 (dd, 1H, 1-H, J = 0.6, 8.51
Hz), 9.88 (broad s, 1H, =NH/-NH-, deuterium oxide-
exchangeable); 13C(1H) nmr (DMSO-d6): ꢂ 179.83 (C-12),
162.50 (C-7a), 161.75 (C-9), 160.35 (C-11), 155.02 (C-6a),
136.52 (C-5), 130.37 (C-11a), 130.11 (C-12a), 129.27 (C-4),
128.88 (C-2), 126.19 (C-3), 125.82 (C-1), 117.68 (C-6), 115.33
(C-12a), 113.54 (C-4a), 95.42 (C-10), 70.03 (C=N); ms: m/z (%)
302 (M+., 100), 301 (M+. – 1, 11), 275 (M+. – HCN, 6), 274 (M+.
– C=O, 13), 67 (H3N+-CC-CN, 3), 66 (H2N-CC-CN, 7), 44
A mixture of 1d (1.86 g, 10 mmol), malononitrile (2.64 g, 40
mmol), sulphur (0.32 g, 10 mmol) and diethylamine (2.92 g, 40
mmol) in dioxan was stirred for 3 hours, then left standing at
room temperature for few days. The resulted precipitate was
crystallized from acetone/dioxane to give 9d as off white
powder (1.125 g, 38%), m.p. 223-225 °C; ir (potassium
bromide): 3718-3296 (=NH groups), 2997 (arom. and aliph. C-
H), 2220 (CN groups), 1647 (C=N), 1616, 1573, 1543 (C=C)
1
cm-1; H nmr (DMSO-d6): ꢂ 2.36 (s, 3H, CH3), 3.35 (s, 1H,
CH(CN)2), 7.68 (d, 1H, 7-H, J = 9.6 Hz), 7.69 (ddd, 1H, 8-H, J =
1.46, 8.42, 8.49 Hz), 7.75 (d, 1H, 5-H, J = 8.79 Hz), 7.78 (d, 1H,
6-H, J = 8.68 Hz), 8.00 (ddd, 1H, 9-H, J = 1.94, 8.11, 8.34 Hz),
8.37 (dd, 1H, 10-H, J = 1.72, 7.77 Hz), 8.99 (broad s, 1H, =NH,
deuterium oxide-exchageable), 9.06 (broad s, 1H, =NH,
deuterium oxide-exchangeable); 13C(1H) nmr (DMSO-d6): ꢂ
+.
(CO2 , 11), 42 (HN=C=NH+., 7).
Anal. Calcd. for C17H10N4O2 (302.30): C, 67.55; H, 3.31; N,
18.54. Found: C, 67.13; H, 3.58; N, 18.22.

1044
E. Sopbué Fondjo and D. Döpp
Vol 43
[4] O. Meth-Cohn and B. Narine, J. Chem. Res-
(M), 3262 (1977); Chem. Abstr., 88, 105040g (1980); O. Meth- Cohn
and B. Narine, Synthesis, 133 (1980).
1,3,14-Triamino-5-imino-5H-benzo[f](2H)chromeno[3,4-h]chi-
nolin-2-carbonitrile (13e).
Ir (potassium bromide): 3458, 3347, 3231 (=NH und –NH2),
2204 (CN), 1619, 1592, 1565, 1501 (C=N, C=C) cm-1; 1H nmr
(DMSO-d6): ꢀ 5.71 (broad s, 2H, 3-NH2, deuterium oxide-
exchangeable), 6.23 (s, 1H, 13-H), 6.47 (broad s, 2H, 1-NH2,
deuterium oxide-exchangeable), 6.65 (broad s, 2H, 14-NH2,
deuterium oxide-exchangeable), 7.14 (dd, 1H, 12-H, J = 1.71,
8.33 Hz), 7.31 (d, 1H, 7-H, J = 8.90 Hz), 7.34 (ddd, 1H, 10-H, J
= 1.55, 6.73, 7.68 Hz), 7.38 (ddd, 1H, 11-H, J = 1.60, 6.90, 8.79
Hz), 7.89 (dd, 1H, 9-H, J = 2.21, 7.09 Hz), 7.95 (1H, d, 8-H, J =
8.97 Hz), 10.03 (broad s, 1H, =NH deuterium oxide-
exchangeable); 13C(1H) nmr (DMSO-d6): ꢀ 158.53 (C-5), 156.38
(C-3), 155.03 (C-6a), 154.25 (C-4a), 151.85 (C-1), 138.94 (C-
14), 132.73 (C-2), 130.73 (C-8), 128.30 (C-9), 127.89 (C-4b),
127.59 (C-11), 123.85 (C-12), 123.64 (C-10), 118.85 (C-12c),
118.56 (C-7), 117.75 (C-12b), 116.66 (C-12a), 115.18 (C-13),
102.84 (C-14a), 86.82 (C-8a), 70.83 (CN); ms: m/z (%) 366
(M+., 75), 365 (M+. – 1, 4), 351 (4), 350 (27), 349 (M+. – NH3,
100).
[5] K. Gewald, E. Schinke and H. Böttcher, Chem. Ber., 99, 94
(1966); Chem. Abstr., 64, 8118 (1966).
[6] K. Gewald, Angew. Chem., 73, 114 (1961); Chem. Abstr.,
55, 12383 (1961).
[7] K. Gewald, Z. Chem., 2, 305 (1962); Chem. Abstr., 58, 6770
(1963).
[8] K. Gewald, Chem. Ber., 98, 3571 (1965); Chem. Abstr., 64,
3451 (1966).
[9] K. Gewald, and E. Schinke, Chem. Ber., 99, 2712 (1966);
Chem. Abstr., 65, 18548 (1966).
[10] V. I. Shvedov and A. N. Grinev, J. Org. Chem. USSR (Eng.
Transl.), 1, 2269 (1965); Chem. Abstr., 64, 1149 (1966).
[11] V. I. Shvedov and A. N. Grinev, USSR Pat. 172,638 (1965);
Chem. Abstr., 64, 700 (1966).
[12] V. I. Shvedov and A. N. Grinev, USSR Pat. 174,638 (1965);
Chem. Abstr., 64, 2056 (1966).
[13] W. Ried and E. Nyiondi-Bonguen, Liebigs Ann. Chem., 1,
134 (1973).
[14] Y. Nakano, H. Yokota, M. Igarashi and S. Sato, Bull. Chem.
Soc. Jpn, 61, 3731 (1988).
[15] M. Igarashi, Y. Nakano and M. Yatsu, Synthesis, 1075
(1984).
Anal. Calcd. for C21H14N6O (366.39): C, 68.85; H, 3.83; N,
22.95. Found: C, 68.86; H, 3.88; N, 22.83.
[16] M. Igarashi, Y. Nakano, M. Yatsu, T. Watanabe and S. Sato,
Synthesis, 68 (1987).
Acknowledgements.
[17] Y. Nakano, M. Igarashi and S. Sato, Acta Crystallogr. Sect.
C, 43, 738 (1987).
The authors thank Deutscher Akademischer Austauschdienst
(DAAD) for granting Dr. E. Sopbué Fondjo a Ph-D fellowship
(grant N° A/96/11507). Technical and financial support from
Gerhard-Mercator-Universität Duisburg is gratefully
acknowledged. Thanks are also due to the University of
Dschang and the Ministry of Higher Education of the Republic
of Cameroon for kindly releasing the above named author for
the implementation of this work. Generous donation of
chemicals by Fonds der Chemischen Industrie is gratefully
acknowledged.
[18] A. J. Fatiadi, Synthesis, 165 (1978).
[19] E. Y. Gudriniece, P. Pastors, A. Levinsh, Dokl. Akad. Nauk.
SSSR, 204, 874 (1972); Chem. Abstr., 77, 114095 (1972).
[20] F. Al-Omran, M. M. Abdel Khalik, H. Al-Awadhi and M. H.
Elnagdi, Tetrahedron, 52, 11915 (1996).
[21] H. Boutome and H. Hartmann, Monatshefte für Chemie, 128,
71 (1997).
[22a] E. Sopbué Fondjo, Dissertation, Gerhard-Mercator-
Universität Duisburg, July 2000.
[22b] E. Sopbué-Fondjo, D. Döpp and G. Henkel, Tetrahedron, in
press.
[23] A. E. Derome, Modern NMR-Techniques for Chemistry
Research, Pergamon Press, Oxford, 1987, a) p. 97, b) p. 129, c) p. 183,
d) p. 245.
[24] R. Adams, J. R. Johnson and C. F. Wilcox, Jr., Laboratory
Experiments in Organic Chemistry, 7th Edition, Macmillan Publishing
Co., New York and Collier Macmillan Publishers, London, 1979, pp.
279-280, 418-419.
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