Diethyl 2-aryl-3-cyanopropene-1,1-dicarboxylates: New versatile precursors in heterocyclic synthesis

Article abstract of DOI:10.1007/PL00010247

An expeditious synthetic route for the title precursor is reported. It provides access to a variety of polyfunctionally substituted pyridines, pyridazines, pyrazolopyridines, thiophenes, and thienopyridines.

Full text of DOI:10.1007/PL00010247

Monatshefte fuÈr Chemie 130, 661±669 (1999)
Diethyl 2-Aryl-3-cyanopropene-
1,1-dicarboxylates: New Versatile Precursors
in Heterocyclic Synthesis
Ayman W. Erian1;Ã, Vivian F. Araki2, Suzan I. Aziz1, and Sherif M. Sherif1
1
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
2
Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt
Summary. An expeditious synthetic route for the title precursor is reported. It provides access to a
variety of polyfunctionally substituted pyridines, pyridazines, pyrazolopyridines, thiophenes, and
thienopyridines.
Keywords. Pyridines; Pyridazines; Pyrazolopyridines; Thiophenes.
Diethyl-2-aryl-3-cyanopropen-1,1-dicarboxylate: Neue vielseitige Vorstufen
fuÈr die Heterocyclensynthese
Zusammenfassung. Eine einfache Synthese zur Darstellung des im Titel genannten Synthons wird
beschrieben. Es vermittelt den Zugang zu polyfunktionell substituierten Pyridinen, Pyridazinen,
Pyrazolopyridinen, Thiophenen und Thienopyridinen.
Introduction
ꢀ-De®cient alkyl reagents are highly reactive and are extensively utilized as
reactants or intermediates for the construction of a variety of unique heterocyclic
ring systems [1±3]. In continuation of our medicinal chemistry program [4±8], we
report herein a simple synthetic methodology for the synthesis of diethyl 2-aryl-3-
cyanopropene-1,1-dicarboxy-lates 3 as versatile precursors for the synthesis of
some hitherto unreported polyfunctionally substituted heterocycles and some of
their fused derivatives.
Results and Discussion
Our attempts to prepare the target reagent 3 via direct condensation of diethyl
malonate (1) with aroylacetonitriles 2 using a variety of acidic or alkaline
conditions failed. However, 3 could be prepared stepwise. Condensation of 1 with
the appropriate acetophenones 4 followed by bromination of the intermediate 5
Ã
Corresponding author

662
A. W. Erian et al.
Scheme 1
with N-bromosuccinimide in dry benzene solution afforded the corresponding
ꢁ-bromo derivatives 6. Reaction of the latter with equimolar proportions of sodium
cyanide in boiling EtOH furnished the target precursors 3 in excellent yields
(Scheme 1).
The versatility of the novel precursors 3 was proven by the following examples.
3a underwent electrophilic substitution upon coupling with an equimolar amount
of the appropriate aryldiazonium chloride to yield the corresponding acyclic
hydrazone coupling products 7a,b. Compounds 7 proved to exist in the hydrazone
from rather than the azo form on the basis of 1H NMR data. Thus, e.g. 7a revealed,
besides the expected signals, the presence of one D2O exchangeable singlet at
ꢂ ˆ 11.20 ppm corresponding to the hydrazone NH function. Furthermore, its UV
spectrum showed absorption maxima at 420 and 330 nm in accordance with those
for hydrazo functions [9, 10]. Re¯uxing of compounds 7a, b in EtOH/NaOAc
resulted in their heterocyclization the corresponding pyridazine-3-carbonitrile
derivatives 8a, b via loss of EtOH (Scheme 2).
Treatment of 3a with an equimolar amount of benzoyl isothiocyanate afforded
the corresponding 1-benzoylpyridine-3-carbonitrile derivative 9. S-Alkylation of 9
with an equimolar amount of chloroacetonitrile resulted in the formation of the
corresponding thieno [3,2-a]pyridine 10.
Compound 3a reacted readily with an equimolar amount of trichloroaceto-
nitrile to yield exclusively the corresponding pyridine-3-carbonitrile 11. The
trichloromethyl moiety of 11 proved to be highly reactive towards nucleophilic
reagents. Thus, fusion of 11 with an excess of hydrazine hydrate resulted in the
formation of the corresponding dipyrazolopyridine 12. Similarly, reaction of 11
with an equimolar amount of phenylhydrazine lead to the corresponding
pyrazolopyridine derivative 13. Also, the trichloromethyl moiety in 11 underwent
facile nucleophilic substitution upon reaction with equimolar amounts of the
appropriate aniline to yield the corresponding 2-aryl-aminopyridines 14. With

Diethyl 2-Aryl-3-cyanopropene-1,1-dicarboxylates
663
Scheme 2
Scheme 3
respect to thiophenes [11±13], the Gewald reaction of 3a was investigated. Thus,
compound 3a reacted with an equimolar amount of elemental sulfur to yield
exclusively the corresponding ethyl thiophene-3-carboxylate 15.
The behaviour of 3 towards ꢁ-cinnamonitriles 16 was also investigated with
respect to the synthesis of highly substituted benzenes. Thus, 3a reacted with
equimolar amounts of the appropriate arylidenemalononitriles 16a,b to yield the
corresponding ethyl benzoate derivatives 18a,b. Formation of 18 is assumed to

664
A. W. Erian et al.
Scheme 4
proceed via Michael addition of the active methylene moiety of 3a to the activated
ꢁ,ꢃ-unsaturated center in 16 to give the acyclic Michael adduct 17 which
spontaneously cyclizes, and aromatizes to the ®nal products 18 (Scheme 4). A
similar reaction has been reported previously [14, 15]. Alternatively, 18a could be
obtained via an independent synthesis involving the condensation of 3a with
benzaldehyde to afford 19. The latter reacted with an equimolar proportion of
malononitrile to yield 18a.
Finally, our study was extended to investigate the behaviour of 3 towards
nitrogen nucleophiles. Thus, 3a reacted with two equivalents of hydrazine
hydrochloride to afford the corresponding pyrazolo[3,4-b]pyridine 21. The reaction
apparently involves the formation of the intermediate 20.
Experimental
1
Melting points are uncorrected; IR spectra (KBr): Pye Unicam SP-1000; H NMR spectra: Varian
Gemini 200 MHz spectrometer, TMS as internal standard; mass spectra: AEI MS 30 mass
spectrometer operating at 70 eV; microanalytical data: Microanalytical Data Unit at Cairo
University; the results were in satisfactory agreement with the calculated data.
Diethyl 2-aryl-3-bromopropene-1,1-dicarboxylates (general procedure)
A mixture of 0.02 mol diethyl malonate (1), 0.02 mol of the appropriate acetophenone 2a, b and 3 g
anhydrous NH4OAc in 80 ml dry benzene containing 5 ml glacial AcOH was re¯uxed under H2O for
7 h. The solvent was distilled off in vacuo, the residue was triturated with 30 ml H2O, and the organic
product was extracted 3 times with 50 ml benzene. The benzene layer was dried over anhydrous
CaCl2 for 24 h, ®ltered off, and the solvent was distilled off in vacuo.
To a solution of 0.02 mol 5 in 50 ml dry benzene, 0.02 mol N-bromo-succinimide were added.
The reaction mixture was re¯uxed for 3 h, and the solvent was evaporated in vacuo. The residue
(highly lachrymatory) was triturated with ethanol; the solid product was collected by ®ltration,
washed with water, dried over CaCl2, and crystallized from an appropriate solvent.

Diethyl 2-Aryl-3-cyanopropene-1,1-dicarboxylates
665
Diethyl 3-bromo-2-phenylpropene-1,1-dicarboxylate (6a; C15H17BrO4)
1
Yield: 4.0 g (59%); m.p.: 56ꢀC (EtOH); Ir: ꢄ ˆ 3000±2950 (CH2), 1715, 1700 (2 CO) cmꢁ1; H
NMR: (DMSO-d6, ꢂ, 200 MHz): 0.95±1.30 (m, 2CH3), 3.95±4.23 (m, 2CH2), 4.40 (s, CH2), 6.79±
‡
7.10 (m, 5Hatom) ppm; MS: m/z (%) ˆ 342 (M , 16), 261 (100), 297 (24).
Diethyl 3-bromo-2-(p-chlorophenyl)propene-1,1-dicarboxylate (6b; C15H16BrClO4)
1
Yield: 4.65 g (62%); m.p.: 64ꢀC (EtOH); IR; ꢄ ˆ 3308±2952 (CH2), 1712, 1700 (2CO) cmꢁ1; H
NMR (DMSO-d6, ꢂ, 200 MHz): 1.05±1.29 (m, 2CH3), 3.90±4.25 (m, 2CH2), 4.56 (s, CH2), 6.88±7.25
(m, 4Harom) ppm.
Diethyl 2-aryl-3-cyanopropene-1,1-dicarboxylates (general procedure)
To a solution of 0.02 mol 6a,b in 50 ml ethanol, 0.02 mol NaCN was added. The reaction mixture
was re¯uxed for 3 h, and the solvent was then evaporated in vacuo. The residue was triturated with
20 ml H2O; the solid product was collected by ®ltration, washed with H2O, dried over CaCl2, and
crystallized from an appropriate solvent.
Diethyl 3-cyano-2-phenylpropene-1,1-dicarboxylate (3a; C16H17NO4)
Yield: 3.90 g (68%); m.p.: 101ꢀC (EtOH); IR: ꢄ ˆ 3000±2950 (CH2), 2221 (CN). 1725, 1710
1
(2 CO) cmꢁ1; H NMR (DMSO-d6, ꢂ, 200 MHz): 0.96±1.35 (m, 2CH3), 3.80±4.23 (m, 2CH2), 4.52
‡
(s, CH2), 6.74±7.20 (m, 5Harom) ppm; MS: m/z (%) ˆ 287 (M , 24), 242 (100), 197 (28).
Diethyl 2-(p-chlorophenyl)-3-cyanopropene-1,1-dicarboxylate (3b: C16H16CINO4)
Yield: 4.56 g (71%); m.p.: 109ꢀC (EtOH); IR: ꢄ ˆ 3010±2955 (CH2), 2218 (CN), 1710, 1700 (2CO)
1
cmꢁ1; H NMR (DMSO-d6, ꢂ, 200 MHz): 1.05±1.29 (m, 2CH3), 3.86±4.29 (m, 4H, 2CH2), 4.82
(s, 2H, CH2), 6.92±7.15 (m, 4Harom) ppm.
Diethyl 3-arylhydrazono-3-cyano-2-phenylpropene-1,1-dicarboxylates (general procedure)
To a stirred solution of 0.005 mol 3a in 50 ml EtOH containing 4 g NaOAc, 0.005 mol of the
appropriate arenediazonium chloride prepared by addition of 0.005 mol NaNO2 to 0.005 mol primary
aromatic amine in 2 ml concentrated HCl at 0±5ꢀC under stirring were added dropwise while cooling
at 0±5ꢀC and stirring. The reaction mixture was left at room temperature fro 2 h; then, the solid
product was collected by ®ltration and crystallized from an appropriate solvent.
Diethyl 3-cyano-2-phenyl-3-phenylhydrazonopropene-1,1-dicarboxylate (7a; C22H21N3O4)
Yield: 1.25 g (64%); m.p.: 186ꢀC (CHCl3); IR: ꢄ ˆ 3350±3318 (NH), 2218 (CN), 1715, 1695
1
(2CO) cmꢁ1; H NMR (DMSO-d6, ꢂ, 200 MHz): 0.95±1.23 (m, 2CH3), 3.87±4.02 (m, 2CH2), 6.72±
7.21 (m, 7Harom), 7.32±7.41 (m, 3Harom), 11.20 (br s, 1H, NH, exchangeable) ppm; MS: m/z
‡
(%) ˆ 391 (M , 18), 345(100), 364(10).
Diethyl 3-(p-chlorophenylhydrazono)-3-cyano-2-phenylpropene-1,1-dicarboxylate
(7b; C22H20ClN3O4)
Yield: 1.44 g (68%); m.p.: 194ꢀC (CHCl3) IR: ꢄ ˆ 3370 (NH), 2220 (CN), 1722, 1700 (2CO) cmꢁ1
;
1H NMR (DMSO-d6, ꢂ, 200 MHz): 0.96±1.25 (m, 2CH3), 3.61±3.93 (m, 2CH2), 6.91±7.33
(m, 6Harom), 7.29±7.40 (m, 3Harom), 10.95 (br s, 1H, NH, exchangeable) ppm.

666
A. W. Erian et al.
Ethyl 2-aryl-6-cyano-2,3-dihydro-3-oxo-5-phenylpyridazine-4-carboxylates (general procedure)
A solution of 0.003 mol 7a,b in 30 ml EtOH containing 1 g NaOAc was heated under re¯ux for 3 h.
The reaction mixture was poured into cold water and neutralized with dilute HCl (pH 7). The
resulting precipitated solid was collected by ®ltration, dried, and crystallized from the appropriate
solvent.
Ethyl 6-cyano-2,3-dihydro-2,5-diphenyl-3-oxopyridazine-4-carboxylate (8a; C20H15N3O3)
1
Yield: 0.60 g (58%); m.p.: 202ꢀC (EtOH); IR: ꢄ ˆ 2218 (CN), 1715, 1665 (2CO) cmꢁ1; H NMR
(DMSO-d6, ꢂ, 200 MHz): 1.22 (t, J ˆ 8.0 Hz, CH3), 4.12 (q, J ˆ 8.2 Hz, CH2), 6.82±7.35 (m,
‡
10Harom) ppm; MS: m/z (%) ˆ 345 (M , 18)
Ethyl 2-(p-chlorophenyl)-6-cyano-2,3-dihydro-3-oxo-5-phenylpyridazine-4-carboxylate
(8b; C20H14ClN3O3)
1
Yield: 0.71 g (62%); m.p.: 218ꢀC (EtOH); IR: ꢄ ˆ 2220 (CN), 1720, 1680 (2 CO) cmꢁ1; H NMR
(DMSO-d6, ꢂ, 200 MHz): 1.16 (t, J ˆ 8.0 Hz, CH3), 4.08 (q, J ˆ 8.2 Hz, CH2), 6.93±7.40 (m,
9Harom) ppm.
Ethyl 1-benzol-5-cyano-1,2-dihydro-6-mercapto-2-oxo-4-phenyl-6-sulfonyl-pyridine-3-carboxylate
(9; C22H16N2O4S)
To a suspension of 0.005 mol NH4SCN in 50 ml dioxane, 0.005 mol benzoyl chloride were added.
The reaction mixture was re¯uxed for 5 min and then treated with 0.005 mol 3a. The mixture was
re¯uxed for 2 h and subsequently poured onto ice/water; the separated solid product was ®ltered off
and crystallized from dioxane.
Yield: 1.31 g (65%); m.p.: 178ꢀC; IR: ꢄ ˆ 2550 (SH), 2221 (CN), 1715, 1675, 1660 (3CO) cmꢁ1
;
1H NMR (DMSO-d6, ꢂ, 200 MHz): 1.21 (t, J ˆ 8.0 Hz, CH3), 3.20 (s, SH), 4.20 (q, J ˆ 8.2 Hz, CH2),
‡
6.82±7.35 (m, 8Harom), 7.42±7.56 (m, 2Harom) ppm; MS: m/z (%) ˆ 404 (M , 19), 353 (100), 298
(80).
Ethyl 2,8-dicyano-3,7-diphenyl-5-oxothiazolo [3,2-a]pyridine-6-carboxylate (10; C24H15N3O3S)
To a suspension of 0.002 mol 9 in 30 ml, EtOH, an aqueous solution of K2CO3 (0.002 mol in 2 ml
H2O) and 0.002 mol chloroacetonitrile were added. The reaction mixture was re¯uxed for 2 h, left to
cool at room temperature, and poured in water. The solid product formed was collected by ®ltration
and crystallized from ethanol.
Yield: 0.54 g (64%); m.p.: 248ꢀC; IR: ꢄ ˆ 2218 (CN), 1710, 1680 (2CO) cmꢁ1
;
1H NMR
(DMSO-d6,ꢂ, 200 MHz): 1.19 (t, J ˆ 8.0 Hz, CH3), 4.18 (q, J ˆ 8.2 Hz, CH2), 6.82±7.45 (m, 10Harom
)
‡
ppm; MS: m/z(%) ˆ 425 (M , 8), 352 (100), 380 (30).
Ethyl 5-cyano-1,2-dihydro-2-oxo-4-phenyl-6-trichloromethylpyridine-3-carboxylate
(11; C16H11Cl3N2O3)
To a solution of 0.005 mol 3a in 30 ml EtOH containing a few drops of Et3N, 0.005 mol
trichloroacetonitrile were added. The reaction mixture was heated under re¯ux for 4 h and left aside
at room temperature overnight. The mixture was poured onto an ice/water mixture, neutralized with
dilute HCl, ®ltered off, washed with water, dried over CaCl2, and crystallized from ethanol.

Diethyl 2-Aryl-3-cyanopropene-1,1-dicarboxylates
667
Yield: 1.15 g (60%); m.p.: 155ꢀC; IR: ꢄ ˆ 2220 (CN), 1710, 1665 (2CO); 1H NMR (DMSO-d6, ꢂ,
200 MHz): 1.10 (t, J ˆ 8.0 Hz, CH3), 4.07 (q, J ˆ 8.2 Hz, CH2), 6.72±7.12 (m, 5Harom), 9.95 (br s,
‡
NH, exchangeable) ppm; MS: m/z (%) ˆ 385 (M , 16), 221(100), 266(60).
5-Oxo-4-phenyl-1,5,6,8-tetrahydropyrazolo [30,40:2,3]pyrazolo [3,4-b]pyridine-3-amine
(12; C13H10N6O)
A mixture of 0.003 mol 11 and 0.006 mol hydrazine hydrate was heated under re¯ux in an oil bath at
140ꢀC for 1 h. The resulting residue was triturated with ethanol to give a solid product that was
collected by ®ltration and crystallized from dioxane.
1
Yield: 0.47 g (59%); m.p.: 245ꢀC; IR: ꢄ ˆ 3420±3380 (NH2, NH), 1665 (CO) cmꢁ1; H NMR
(DMSO-d6, ꢂ, 200 MHz): 3.22 (br s, NH2, exchangeable), 6.24 (s, NH, exchangeable), 6.45 (s, NH,
exchangeable), 6.81±7.25 (m, 5Harom), 8.31 (s, NH, exchangeable) ppm.
Ethyl 1,2-dihydro-4,6-diphenyl-2-oxopyrazolo[3,4-b]pyridine-5-amine (13; C21H18N4O3)
To a solution of 0.003 mol 11 in 30 ml dioxane, 0.003 mol phenylhydrazine were added. The reaction
mixture was heated under re¯ux for 3 h and then left with stirring overnight at room temperature.
The mixture was poured onto 20 ml water; the solid product was ®ltered off and crystallized from
ethanol.
1
Yield: 0.72 g (64%); m.p.: 175ꢀC; IR: ꢄ ˆ 3450±3330 (NH2, NH), 1710, 1675 (2CO) cmꢁ1; H
NMR (DMSO-d6, ꢂ, 200 MHz): 0.95 (t, J ˆ 8.0 Hz, CH3), 4.01 (q, J ˆ 8.2 Hz, CH2), 4.56 (br s, NH2,
‡
exchangeable), 6.82±7.41 (m, 10Harom) ppm; MS: m/z(%) ˆ 274 (M , 21), 252 (100), 329 (80).
Ethyl 6-arylamino-5-cyano-1,2-dihydro-2-oxo-4-phenylpyridine-3-carboxylates (general procedure)
To a solution of 0.002 mol 11 in 30 ml dioxane, 0.002 mol aromatic amine was added. The reaction
mixture was heated under re¯ux for 6 h. The solid product formed upon dilution with water was
collected by ®ltration and crystallized from an appropriate solvent.
Ethyl 5-cyano-1,2-dihydro-2-oxo-4-phenyl-6-phenylaminopyridine-3-carboxylate
(14a; C21H17N3O3)
Yield: 0.40 g (55%); m.p.: 177ꢀC (EtOH); IR: ꢄ ˆ 3450±3420 (NH), 2221 (CN), 1715, 1665
(2CO) cmꢁ1; 1H NMR (DMSO-d6, ꢂ, 200 MHz): 1.12 (t, J ˆ 8.0 Hz, CH3), 4.15 (q, J ˆ 8.2 Hz, CH2),
6.28 (br s, NH, exchangeable), 6.81±7.38 (m, 10Harom), 11.90 (br s, NH, exchangeable) ppm; MS:
‡
m/z (%) ˆ 359 (M , 9), 221 (100), 266 (60).
Ethyl 6-(p-chlorophenylamino)-5-cyano-1,2-dihydro-2-oxo-4-phenyl-pyridine-3-carboxylate
(14b; C21H16ClN3O3)
Yield: 0.49 g (62%); m.p.: 205ꢀC (EtOH); IR: ꢄ ˆ 3430±3415 (NH), 2218 (CN), 1710, 1675 (2CO)
1
cmꢁ1; H NMR (DMSO-d6, ꢂ, 200 MHz): 1.10 (t, J ˆ 8.0 Hz, CH3), 4.20 (q, J ˆ 8.3 Hz, CH3), 6.31
(br s, NH, exchangeable), 6.92±7.29 (m, 9Harom), 11.32 (br s, NH, exchangeable) ppm.
Ethyl 5-cyano-2-hydroxy-4-phenylthiophene-3-carboxylate (15; C14H11NO3S)
A mixture of 0.005 mol 3a and 0.005 mol elemental sulfur in 30 ml ethanol containing 5 drops
anhydrous Et3N was re¯uxed for 6 h. The reaction mixture was poured in cold water and neutralized

668
A. W. Erian et al.
with dilute HCl (pH 7). The resulting solid precipitate was collected by ®ltration, washed with water,
and crystallized from ethanol.
Yield: 0.93 g (68%); m.p.: 196ꢀC; IR: ꢄ ˆ 3500±3330 (OH), 2222 (CN), 1715 (CO) cmꢁ1
;
1H NMR (DMSO-d6, ꢂ, 200 MHz): 1.20 (t, J ˆ 8.0 Hz, CH3), 3.05 (s, OH, exchangeable), 4.12
‡
(q, J ˆ 8.2 Hz, CH2), 6.91±7.25 (m, 5Harom) ppm; MS: m/z (%) ˆ 273 (M , 35), 145 (100),
228 (46).
Ethyl 4-aryl-3,5-dicyano-2-hydroxy-6-phenylbenzoates (general procedure)
A solution of 0.003 mol 3a and 0.003 mol 16a, b in 30 mol EtOH containing a few drops of Et3N was
heated under re¯ux for 3 h. The reaction mixture was evaporated in vacuo, triturated with cold water,
and neutralized with dilute HCl. The solid product precipitated was collected by ®ltration, dried over
CaCl2, and crystallized from the appropriate solvent.
Ethyl 3,5-dicyano-4,6-diphenyl-2-hydroxybenzoate (18a;C23H16N2O3)
Yield: 0.73 g (66%); m.p.: 182ꢀC (EtOH); IR ꢄ ˆ 3500±3450 (OH), 2220, 2216 (2CN), 1700
(CO) cmꢁ1
;
1H NMR (DMSO-d6, ꢂ, 200 MHz): 0.95 (t, J ˆ 8.0 Hz, CH3), 2.95 (s, OH,
‡
exchangeable), 4.05 (q, J ˆ 8.3 Hz, CH2), 6.75±7.38 (m, 10Harom) ppm; MS: m/z (%) ˆ 368 (M ,
15), 296 (100), 323 (72).
Ethyl 4-(p-chlorophenyl)-3,5-dicyano-2-hydroxy-6-phenylbenzoate (18b; C23H15ClN2O3)
Yield: 0.72 g (60%); m.p.: 216ꢀC (EtOH); IR: ꢄ ˆ 3480±3445 (OH), 2218, 2212 (2CN), 1695
(CO) cmꢁ1; 1H NMR (DMSO-d6, ꢂ 200 MHz): 1.05 (t, J ˆ 8.0 Hz, CH3), 3.09 (s, OH, exchangeable),
4.10 (q, J ˆ 8.2 Hz, CH2), 6.90±7.35 (m, 9Harom) ppm.
Diethyl 2,4-diphenyl-3-cyanobuta-1,3-diene-1,1-dicarboxylate (19; C23H21NO4)
Method A. A mixture of 0.003 mol 3a and 0.003 mol benzaldehyde in 30 ml ethanol containing a few
drops of Et3N was re¯uxed for 3 h. The reaction mixture was then poured in cold water and
neutralized with dilute HCl. The solid product formed was ®ltered off and crystallized form ethanol.
Yield: 0.76 g (68%); m.p.: 134ꢀC; IR: ꢄ ˆ 2220 (CN), 1710, 1695 (2 CO), 1650 (C=C) cmꢁ1; 1H
NMR (DMSO-d6, ꢂ, 200 MHz): 0.95±1.34 (m, 2CH3), 3.80±4.20 (m, 2CH2), 6.71±7.32 (m,
‡
11Harom‡ylidene CH); MS: m/z (%) ˆ 375 (M , 18), 284 (100), 330 (80).
Method B. A mixture of 0.002 mol 19 and 0.002 mol malononitrile in 25 ml ethanol containing a
few drops of Et3N was re¯uxed for 3 h. The reaction mixture was poured in cold water and
neutralized with dilute HCl. The solid product was collected by ®ltration and crystallized from
EtOH. It was found to be identical (m.p., mixed m.p., and IR spectrum) with an authentic sample
prepared according to method A.
5-Hydroxy-4-phenylpyrazolo[3,4-b]pyridine-1,2-diamine (21; C12H11N5O)
To a solution of 0.003 mol 3a in 30 ml ethanol, 0.006 mol hydrazine hydrochloride were added. The
reaction mixture was heated under re¯ux for 3 h; the precipitated solid product formed at room
temperature was ®ltered off, washed thoroughly water, and crystallized from ethanol.
1
Yield: 0.43 g (60%); m.p.: 200ꢀC; IR: ꢄ ˆ 3550±3350 (OH, NH2) cmꢁ1; H NMR (DMSO-d6, ꢂ,
200 MHz): 3.25 (br s, 2NH2, exchangeable), 4.61 (br s, OH, exchangeable), 6.91±7.23 (m,
‡
5Harom) ppm; MS: m/z (%) ˆ 241 (M , 12), 147 (100), 226 (71).

Diethyl 2-Aryl-3-cyanopropene-1,1-dicarboxylates
669
References
[1] Erian AW (1993) Chem Rev 93: 1991 and references cited therein
[2] Sherif SM, Erian AW (1996) Heterocycles 43: 1085 and references cited therein
[3] Simpkins NS (1990) Tetrahedron 46: 6951
[4] Erian AW, Sherif SM, Alassar AA, Elkholy YM (1994) Tetrahedron 50: 1877
[5] Sherif SM, Youssef MM, Mobarak KM, Abdel-Fattah AM (1993) Tetrahedron 49: 9561
[6] Erian AW (1993) J Chem Res (S) 8; (M) 155
[7] Erian AW, Gohary SE, Manhi FM (1999) Pharmazie (in press)
[8] Erian AW, Sherif SM (1995) Heterocycles 41: 2195
[9] Yao HC, Resnick PJ (1962) J Am Chem Soc 84: 3514
[10] Yao HC (1964) J Org Chem 29: 2959
[11] Erian AW (1993) J Chem Res (S) 352; (M) 2301
[12] Sherif SM (1996) Monatsh Chem 127: 955
[13] Erian AW, Abu-Shanab FA (1999) Bull Chem Soc Jpn (in press)
[14] Figueras J (1996) J Org Chem 31: 803
[15] Soto JL, Seoane C, Zammorano P, Javier F (1981) Synthesis 529
Received June 25, 1998. Accepted (revised) September 15, 1998