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536 J. CHEM. RESEARCH (S), 1999

Utility of 3-Aminocrotononitrile in the Synthesis J. Chem. Research (S),

1999, 536^537
of New Methyl 1,4-Dihydropyridine, J. Chem. Research (M),
1999, 2354^2364
Methylquinoline and Thiophene Derivatives:
Reactivity of the Methyl Function in Alkyl
1,4-Dihydropyridine and Methyl Quinoline
Derivatives Towards Some Electrophilic
Reagents
Ibrahim Saad Abdel Ha¢z,*a Elham Sayed Darwishb and
Fivian Farouk Mahmoudc
a
Department of Chemistry, Faculty of Education, Suez Canal University, Arish, Egypt
b
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
c
Department of Chemistry, Faculty of Science, El-Azhar University, Cairo, Egypt

The methyl function in some newly prepared methyl 1,4-dihydropyridine and methyl quinoline derivatives proves
to be highly active towards some electrophiles.
Published on 01 January 1999. Downloaded on 19/09/2013 23:08:32.

A literature survey revealed that 2-aminocrotononitrile con- 3-aminocrotononitrile towards aromatic aldehydes,15
denses with aromatic aldehydes to a¡ord heteroaromatic aldehydes16 and aliphatic ketones,
1,4-dihydropyridine derivatives.15 Recently, we have found 3-aminocrotononitrile 1 reacted with salicylaldehyde 7a
that heteroaromatic aldehydes condense with in acidic medium to give a 2:2 adduct formulated as the
3-aminocrotononitrile 1 to a¡ord pyridine derivatives.16 1,4-dihydropyridine derivative 16a. Compound 16 is
This result promoted us to focus on the behaviour of assumed to be formed via initial condensation of
3-aminocrotononitrile towards some other carbonyl com- salicylaldehyde with one molecule of 1 to yield the unstable
pounds. Thus, it has been found that acetone 2a condensed ylidene derivative 12 which, in turn, reacts with another
readily with 3-aminocrotononitrile 1 to a¡ord a 1:2 adduct molecule of 1 giving 13 which cyclizes to 14 and loses
formulated as the 2,4,4,6-tetramethyl-1,4-dihydropyridine NH3 to a¡ord 15. Compound 15 reacts further with another
derivative 6a. Establishing structure 6a was based on its molecule of 7a to give the dihydropyridine derivative 16a.
spectral data. Formation of compound 6a is assumed to Attempts to isolate 15 failed (Scheme 2).
be via initial condensation of acetone with one molecule
of 1 to yield the unstable ylidene derivative 3a which, in
turn, reacts with another molecule of 1 giving intermediate H2N
Me
4a which cyclizes into 5, which then loses NH3 to yield CN H NH2 OH
Ar ArCHO 7a
6a. Similarly, butanone condenses with 1 to a¡ord CN
1,4-dihydro-4-ethyl-2,4,6-trimethylpyridine-3,5-dicarbonitrile Me NH
7a,b
NC
basic
Me medium OH
6b (Scheme 1). H
12 1 8
R1 R2 R1 –H2O
NC CN 1
CN R1 CN
H+ R2 1 Me
+ O CN
–H2O Me Me
H2N Me R2 HN Me Ar H 2N
H2N NH2
1 2 3 4 NC CN O
7, 16a, Ar = C6H4OH-2
b, Ar = styryl
Me Me
R2 R1 R2 R1 H2N NH2
NC CN NC CN 13 9
2–6a R1 = R2 = Me
H –H2O
–NH3 b R1 = Me, R2 = Et
Me N NH2 Me N Me
H H Ar Me Me CN
Me
5 6 NC CN CN
N
H N

Scheme 1 Me N NH2
H Me
14
The behaviour of salicylaldehyde 7a towards 1 was found 11 10
to be dependent upon the reaction conditions. Thus, –NH3

salicylaldehyde 7a reacts with 3-aminocrotononitrile 1 in Ar Ar

basic medium to give a 1:1 adduct formulated as the quino- NC CN NC CN
line derivative 11 which has identical properties to that of 7a,b

an authentic sample.17 Compound 11 is assumed to be

Me N Me Me N CH CHAr
formed via nucleophilic attack of 1 at the carbonyl carbon H H
and subsequent cyclization via loss of two water molecules. 15 16a, Ar = C6H4OH-2
In contrast to this and to the reported behaviour of b, Ar = styryl

* To receive any correspondence. Scheme 2

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J. CHEM. RESEARCH (S), 1999 537

Similar to the behaviour of 1 towards salicylaldehyde 7a samples prepared from the condensation of 11 with
in acidic medium, 3-aminocrotononitrile 1 reacted with aldehydes 7c^f (Scheme 4).
cinnamaldehyde 7b to a¡ord the dihydropyridine derivative
16b (Scheme 2). Me Me
Furthermore, the behaviour of 1 towards active methyl- CN NC CN
ene reagents and sulfur was also investigated and found
NC CN
to a¡ord new thiophene derivatives. Thus, when a mixture 11 6a
N Me N
of 1, ethyl acetoacetate and sulfur was re£uxed in H
sodium/dioxan, a product with molecular formula NC
Ar
Ar NC
Ar
C10 H11 NO2 S 20a was obtained.20 Formation of 20a from
CN CN
1, ethyl acetoacetate and elemental sulfur appears to be 24 21 22
an extension of Gewald's synthesis of substituted
thiophenes21 (Scheme 3). Similarly, acetylacetone 17b –CH2(CN)2
–CH2(CN)2

reacted with 1 and elemental sulfur to give the thiophene

Me Me
derivative 20b. CN NC CN
11 6a
ArCHO
O O N CH CHAr
O Me N CH CHAr
CN 7c Ar = C6H5 H
S8 25 23
NH R Me
+ d Ar = C6H4Cl-p
Published on 01 January 1999. Downloaded on 19/09/2013 23:08:32.

R 21,23,25a Ar = C6H5
–NH3 SH e Ar = 2-thienyl
Me b Ar = C6H4Cl-p
Me O Me
f Ar = 2-furyl c Ar = 2-thienyl
17a, R = EtO 1 CN
18 d Ar = 2-furyl
b, R = Me
O O
OH Me
Me Scheme 4
R R
S S
–H2O
Me Me
CN CN Techniques used: IR, 1 H NMR, mass spectrometry and elemental
19 20a, R = EtO analysis
b, R = Me

Scheme 3 References: 25

Alkyl functions in p-de¢cient alkylheteroaromatics are
reactive towards electrophiles under mild conditions.10;22
Encouraged by this, we investigated the reactivity of the
methyl functions in 6a and 11. Thus, it has been found that,
in contrast to the reported formation of benzoazines in the
reaction of methylazinylcarbonitriles with arylidenemalono-
nitrile 21, the reaction of 6a with arylidenemalononitriles
21a^c gave ylidene derivatives 23a^d. Compounds 23a^d
were found to be identical with authentic samples prepared
from the condensation of 6a with aromatic aldehydes 7c^f
(Scheme 4).
Similarly, 2-methylquinoline-3-carbonitrile 11 reacted
with arylidenemalononitriles 21a^d to a¡ord the ylidene
derivatives 25a^d which were identical with authentic
Received, 17th March 1999; Accepted, 2nd June 1999
Paper E/9/02106J
References cited in this synopsis
10 M. H. Elnagdi, E. A. A. Ha¢z and A. W. Erian, Heteroatom,
1995, 13, 179.
15 A. Hantzsch, Liebigs Ann. Chem., 1882, 215.
16 I. S. A. Ha¢z, unpublished work.
17 M. P. Moon, A. P. Komin, J. F. Wolfe and G. F. Morris, J.
Org. Chem., 1983, 48, 2392.
20 A. W. Erian, J. Chem. Res., 1993, (S) 8; (M) 0155.
21 K. Gewald, E. Schnike and H. Bottcher, Chem. Ber., 1966, 99.
22 M. H. Elnagdi, A. M. Negm and K. U. Sadek, Synlett., 1994,
27.