New data about the reaction of benzyolacetonitrile with malononitrile and its self-condensation

Article abstract of DOI:10.1002/jhet.5570430102

The reactions of benzoylacetonitrile with malononitrile in refluxing pyridine and its self condensation under fusion conditions in the presence of ammonium acetate and in refluxing pyridine were reinvestigated. New data were found and plausible mechanisms to account for the formation of the products are suggested.

Full text of DOI:10.1002/jhet.5570430102

Jan-Feb 2006
New Data About the Reaction of Benzyolacetonitrile with
Malononitrile and Its Self-condensation
7
Fathy M. Abdelrazek* and Farid A. Michael
Chemistry Department, Faculty of Science, Cairo University Giza, Egypt
Received March 11, 2005
The reactions of benzoylacetonitrile with malononitrile in refluxing pyridine and its self condensation
under fusion conditions in the presence of ammonium acetate and in refluxing pyridine were reinvestigated.
New data were found and plausible mechanisms to account for the formation of the products are suggested.
J. Heterocyclic Chem., 43, 7 (2006).
In the last few years we have been involved in a program
showed a molecular ion peak in the mass spectrum at
m/z=193. The IR spectrum of this product showed three
aiming at the synthesis of functionally substituted hetero-
cyclic compounds of expected biological activity to be
used as biodegradable agrochemicals from laboratory
available starting material [1-4]. During the present phase
of our research some functionally substituted pyridazine
derivatives were required for biological activity evalua-
tion. Benzoylacetonitrile 1 seemed to be a good precursor
to fulfill our objective via its condensation with malononi-
trile or its self-condensation to obtain the Knoevenagel
condensation products 2 and 5a respectively (Scheme 1).
These two compounds, by virtue of their active methylene
groups, can undergo azo coupling with different aromatic
and heteroaromatic diazonium salts followed by cycliza-
tion to afford our target pyridazine derivatives. During our
literature search we have found a complete research paper
dealing with the preparations of the desired compounds
-
1
cyano absorption bands at ν = 2220, 2215 and 2205 cm .
1
The H nmr spectrum revealed only two signals at δ = 3.1
(s, 2H) and 7.2-7.52 (m, 5H) ppm. Based on these data the
condensation product 2 was assigned to this product
(structure 2 in the original paper [5], mp 80 °C and no nmr
data given). The second product (mp. 236 °C) showed a
molecular ion peak in its mass spectrum at m/z = 211. The
ir spectrum of this product showed absorption bands at ν =
-
1
3420-3160 and 2210 cm attributable to NH, NH and CN
2
1
groups. The H nmr spectrum of this compound showed
signals at δ = 6.85 (s, 1H), 7.15 (br.s, 2H, exchangeable),
7.18-7.52 (m, 5H) and 9.85 (s, 1H, exchangeable). Based
on these data the pyran structure 3 was assigned to this
product (not mentioned in the original paper [5], most
likely not separated by the authors).
[
5]. Therefore we started to prepare some of these com-
To account for the formation of these two products from
1 and malononitrile the reactants apparently undergo two
competitive reactions. A Knoevenagel condensation reac-
tion which leads directly to compound 2; and a Michael
addition of the active methylene of malononitrile to the
cyano function of 1 will lead to the tautomerized interme-
diate 4a/4b which undergoes a 6-exo-dig cyclization [6] to
afford the iminopyran 3 as shown in Scheme 1.
pounds following the same synthetic pathways described
in this paper [5]. It should be stated that it was not intended
to reinvestigate this work but rather to prepare the required
compounds; however the new data encountered during our
preparations seemed worth publishing and is reported in
the present paper.
In our hands compound 1 reacts with malononitrile in
refluxing pyridine (see experimental) to afford two prod-
ucts (tlc analysis). The first product (brown; mp. 83 °C)
On the other hand, Elnagdi et. al. [5] claimed that they
could successfully dimerize compound 1 and assigned

8
F. M. Abdelrazek and F. A. Michael
Vol. 43
structure 5a (Scheme 1) for the product (structure 7 in their
paper; it is a self condensation product and not a dimer as
they called it). It should be mentioned that the authors have
provided all possible evidence in their discussion that this
product exists predominantly (in both solid state and in
solution) in the dienol form 5b (structure 8 in their paper),
however all the reactions provided after, and the spectral
data given contradict this conclusion and are based on
structure 5a (7 in the original paper) as the predominant
one. This contradiction caused some doubt in the factual
accuracy of this work; and therefore we have turned our
aim from the preparation of the compounds to the reinves-
tigation of this work.
account for the formation of these three products from 1,
again it is assumed that compound 1 undergoes two com-
petitive reactions: A Knoevenagel self-condensation of
two molecules of 1 to afford the tautomeric pair 5a/5b,
which undergoes a 6-exo-dig cyclization [6] to afford the
iminopyran 6 (as shown in Scheme 1). In presence of
ammonium acetate and under fusion conditions compound
6 is apparently attacked by ammonia and the ring is opened
to afford the acyclic tautomeric pair 7a/7b. Recyclization
of 7a through loss of water will lead to the iminopyridine
8a, which can in principle tautomerize to the amino pyri-
dine 8b, however all data suggest the imino structure 8a;
while recyclization of 7b via reelimination of ammonia
leads to the 2-pyridone derivative 9. Compound 8a has
been previously described in the literature [7].
In our hands we could isolate three novel heterocyclic
compounds from the fusion of 1 with ammonium acetate at
1
20 °C (the same reaction conditions as described in ref.
The other possible direction is a Michael addition of the
active methylene of one molecule of 1 to the cyano func-
tion of another to afford the 1,5-dione intermediate 10,
which is transformed into the pyridine derivative 11 under
[
5]). On the basis of the analytical and spectral data of
these three products, the pyridine structures 8a, 9 and 11
were assigned to these compounds (cf. experimental). To

Jan-Feb 2006
New Data About the Reaction of Benzyolacetonitrile with Malononitrile
9
the effect of ammonia [8]. All the reactions described on
the claimed structure 5a (7 in the original paper [5]) and all
the structures derived from it and the spectral data pre-
sented to support these structures seem to be imaginary
and fabricated.
Refluxing compound 1 in pyridine we could isolate a
dark yellow compound. Elnagdi et. al. [5] claimed that
this compound is the so called trimer and assigned struc-
ture 14 (structure 6 in the original paper), however our
isolated product had the same melting point as mentioned
The Reaction of Benzoylacetonitrile (1) with Malononitrile.
To a solution of benzoylacetonitrile 1 (4.35 g, 30 mmol) in ca. 30
ml of pyridine was added malononitrile (1.98 g, 30 mmol) and the
reaction mixture was refluxed at its boiling point for 3 h then left to
cool to room temperature. The reaction mixture was then poured on
ice cold water whereby a brown precipitate appeared, which was fil-
tered off and recrystallized from ethanol / DMF and identified as 2.
The mother liquor was acidified with ice cold HCl till just neutral
(
pH paper) at which point a yellow crystalline product is formed,
collected by filtration, recrystallized from ethanol and identified as
. The overall yield of the reaction is ca. 80% with a ratio of 2:1
respectively.
3
[
5] but the ir spectrum of this product did not show any
absorption bands that can be attributed to amino or car-
bonyl functions and only one strong cyano absorption
band is revealed (cf. experimental). Furthermore the H
2
-Cyano-3-phenylpent-2-enedinitrile (2).
1
Brown powder, yield 3.15 g (~54 %); mp. 83-84 °C(lit. 80
°
C) [5]. (EtOH / DMF);. Ir: 2220, 2215 and 2205 cm-1 (3
nmr spectrum of this product showed only an aromatic
multiplet. Mass spectral measurements showed that this
compound has a molecular weight of 381, which is con-
sistent with three molecules of 1 losing three molecules
of water. On the basis of these data it was assumed that
three molecules of 1 underwent three condensations with
each other to afford 13 presumably via the intermediacy
of 12 (Scheme 1). It should be mentioned that Elnagdi et.
al. [5] had established their structure 14 (6 in the original
paper) based on the inactivity of the product toward
reagents expected to effect ready condensation (e.g., with
hydrazine and hydroxylamine). Contrary to this structure
1
CN); H nmr: 3.1 (s, 2H) and 7.2-7.52 (m, 5H); ms: m/z 193
(
molecular ion).
Anal. Calcd. for C H N : C, 74.60; H, 3.65; N, 21.75. Found:
1
2 7 3
C, 74.5; H, 3.7; N, 21.8.
4
-Amino-2-imino-6-phenyl-2H-pyran-3-carbonitrile (3).
Yellow crystalline solid, yield 1.5 g (~26 %); mp. 236-237 °C
-
1
1
(
EtOH); ir: 3420-3160 (NH & NH ), 2210 cm (CN); H nmr:
2
6
5
.85 (s, 1H, pyran 5-H); 7.15 (br. s, 2H, NH ) and 7.18-7.52 (m,
H, arom. H); 9.85 (s, 1H, NH); ms: m/z 211 (molecular ion).
2
Anal. Calcd. for C12H N O: C, 68.24; H, 4.29; N, 19.89.
9
3
Found: C, 68.5; H, 4.6; N, 20.2.
The Self-condensation and Self-dimerization of (1).
1
4 should undergo such condensations by its claimed car-
bonyl group and our structure 13 better fits with this
statement. A conclusive evidence of structure 13 was
obtained from the C nmr of this product which showed
Benzoylacetonitrile 1 (4.35 g, 30 mmol) was mixed with
ammonium acetate (1.6 g, 30 mmol) in a dry round bottom flask.
The reaction mixture was heated on an oil bath at 120 °C for 3 h
after which it was allowed to cool to room temperature. The solid
mass thus obtained was triturated with ethanol where it dissolved.
The solution was poured onto ice-cold water and acidified with
cold acetic acid till neutral. The solid precipitate thus obtained
was collected by filtration and washed with cold water. The over-
all yield of the reaction is ca. 75%. TLC analysis showed that this
reaction product contains three compounds, which were sepa-
rated by column chromarography on silica gel with petroleum
ether/ethyl acetate (4:1) as eluent. Compound 9 was collected
first followed by 8a and then 11.
1
3
only seven signals at δ = 110.2 (s), 115.9 (s), 127.2 (d),
1
28.5 (d), 129.9 (d), 137.1 (s), 150.1 (s) ppm, which is
applicable with structure 13 beside the correct elemental
analysis (cf. experimental). If the structure was 14
(
claimed 6) a carbonyl signal would have appeared in the
1
3
C nmr of this product at δ below 180 ppm similar to
that of benzophenone [9]. The claimed path from 5a to 14
7 to 6 in the original paper [5]) is not real since neither
compound exists.
(
6
-Imino-2,4-diphenyl-1,6-dihydropyridine-3-carbonitrile (8a).
EXPERIMENTAL
Yellow crystals, yield 1.2 g (22 %); mp. 218-220 °C
(
EtOH/DMF) (lit. 217-218 °C, [7]); ir: 3410- 3280 (NH), and
-
1 1
Melting points were determined on an electrothermal (9100)
apparatus and are uncorrected. IR spectra were recorded as KBr
2212 (CN), 1618 (C=N) cm ; H nmr: 6.25 (s, 1H, CH); 7.2-7.8
(m, 10H, arom. H); 9.65 (s, 1H, NH); 11.2 (s, 1H, ring NH); ms:
m/z 271 (molecular ion).
1
pellets on a Perkin Elmer 1430 spectrophotometer. The H and
C-nmr spectra were recorded on a Varian Gemini 300 MHz
1
3
Anal. Calcd. For C18H13N : C, 79.68; H, 4.83; N, 15.49.
3
spectrometer in deuterated DMSO using TMS as internal stan-
dard and chemical shifts are expressed in δ (ppm) values.
Assignments were made by correlation of the off-resonance
decoupled 13C-nmr spectra and determination of the H chemical
shifts. Mass spectra were taken on a Shimadzu GCMS-GB 1000
PX (70 eV). Elemental analyses were carried out by the
Microanalytical Center at Cairo University. The reactions were
followed by tlc carried out on a silica gel aluminium sheets using
petroleum ether- ethyl acetate as eluent.
Found: C, 79.5; H, 4.7; N, 15.2.
6
-Oxo-2,4-diphenyl-1,6-dihydropyridine-3-carbonitrile (9).
1
Dark yellow crystals, yield 0.85 g (15 %); mp. 286-288 °C
(EtOH / DMF); ir: 3350- 3280 (NH), and 2230 (CN), 1675
-
1 1
(C=O) cm ; H nmr: 6.65 (s, 1H, CH); 7.1-7.8 (m, 10H, arom.
H); 11.45 (s, 1H, ring NH); ms: m/z 272 (molecular ion).
Anal. Calcd. For C H N O: C, 79.39; H, 4.44; N, 10.29.
1
8 12 2
Found % C, 79.4; H, 4.7; N, 10.2.

10
F. M. Abdelrazek and F. A. Michael
Vol. 43
4
/
-Amino-2,6-diphenylnicotinonitrile (11).
and the kind hospitality of Prof. Dr. Peter Metz, Institut fur
Organische Chemie, TU Dresden is highly appreciated.
Brown fine crystals, yield 1.4 g (25 %); mp. 220-222 °C (EtOH
-1 1
DMF); ir: 3430- 3285 (NH ), and 2215 (CN), cm ; H nmr: 6.9
2
(
s, 1H, CH); 7.15 (br. s, 2H, NH ); 7.25-8.0 (m, 10H, arom. H);
REFERENCES AND NOTES
2
ms: m/z 271 (molecular ion).
Anal. Calcd. For C18H13N : C, 79.68; H, 4.83; N, 15.49.
Found: C, 79.4; H, 4.6; N, 15.3.
*
e-mail: prof_fmrazek@yahoo.com
3
[
1] N. H. Metwally, F. M Abdelrazek, J. Prakt. Chem. Chem
Zeitung, 340, 676, (1998).
1
,3,5-Tricyano-2,4,6-triphenylbenzene (13).
[2] F. M. Abdelrazek, A. M. Salah-Eldin, A. E. Mekky,
Tetrahedron, 57, 1813, (2001); F. M Abdelrazek, A. M. Salah-Eldin,
A. E. Mekky, Tetrahedron, 57, 6787, (2001).
3] F. M. Abdelrazek, N. H. Metwally, Afinidad, 61, 134,
2004).
4] F. M. Abdelrazek, P. Metz, E. K. Farrag, Arch. Pharm.
Pharm. Med. Chem. (Weinheim), 337, 482, (2004).
[5] G. E. H. Elgemeie, H. A. Elfahham, S. Elgamal, M. H.
Elnagdi, Heterocycles, 23, 1999, (1985).
[6] J. E. Baldwin, J. Chem. Soc. Chem. Commun.; 734,
1976).
7] A. Sakurai, H. Midorikawa, Bull. Chem. Soc. Jpn., 42,
20, (1969).
Benzoylacetonitrile 1 (4.35 g, 30 mmol) was refluxed in pyri-
dine for 2 h and then left to cool to room temperature where a yel-
lowish green crystalline product appeared. This product was col-
lected by filtration and washed thoroughly with ethanol and recrys-
tallized from ethanol/DMF to afford 3.5 g (yield= 80 % relative to
[
(
[
1; 30 % relative to 13) of pure compound 13, mp. 283-284 °C
1
(
EtOH/DMF) (lit. mp 285 °C) [5]; ir: 2235 (CN); H nmr: 7.15-7.6
m, arom. H). 1 C nmr 110.2 (s), 115.9 (s), 127.2 (d), 128.5 (d),
29.9 (d), 137.1 (s), 150.1 (s); ms: m/z 381 (molecular ion).
Anal. Calcd. for C27H15N : C, 85.02; H, 3.96; N, 11.02.
3
(
(
1
[
3
2
Found: C, 84.8; H, 4.1; N, 11.3.
[
8] T. R. Kelly, H-ting Liu, J. Am. Chem. Soc., 107, 4998,
1985).
9] M. Hesse, H. Meier and B. Zeeh. Spektroskopische
Methoden in der Organischen Chemie, 4 Auflage, George Thieme
Verlag, Stuttgart. New York, pp. 188 (1991).
(
Acknowledgement.
[
te
F. M. Abdelrazek thanks the Alexander von Humboldt- foun-
dation for granting a research fellowship (July-September 2005),