Chemistry of 2-arylhydrazonopropanals: Novel synthesis of 1,6-dihydropyridazines and 5-heteroaryl substituted pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyridines

Article abstract of DOI:10.1055/s-2001-17522

The reaction of 2-arylhydrazonopropanals 1a-d with dimethyl acetylenedicarboxylate in anhydrous dichloromethane in the presence of triphenylphosphine afforded 1,6-dihydropyridazines 2a-d. Compound 1a reacted with dimethyl acetylenedicarboxylate in refluxing acetic acid yielding the corresponding Michael adduct 4. Whereas compound 1d failed to react in acetic acid with diphenylacetylene, its reaction with the same reagent in anhydrous dichloromethane in the presence of triphenylphosphine afforded the Michael adduct 3. Compounds 2b-d reacted with hydrazine hydrate affording the corresponding pyridazino[3,4-d]pyridazines 6b-d. 2-Arylhydrazonopropanals 1a,b reacted with 5-methyl-1H-pyrazol-3-amine in ethanol yielding the corresponding condensation products 8a,b, which cyclized to the 7-substituted 2-methyl-6-phenylazopyrazolo[1,5-a]pyrimidines 9a,b and 4-substituted 3-methyl-5-phenylazopyrazolo[3,4-b]pyridines 10a,b on refluxing in acetic acid. 2-Phenylhydrazonopropanal 1a reacted with p-benzoquinone yielding the resorcinol derivative 12.

Full text of DOI:10.1055/s-2001-17522

PAPER
1861
Chemistry of 2-Arylhydrazonopropanals: Novel Synthesis of 1,6-
Dihydropyridazines and 5-Heteroaryl Substituted Pyrazolo[1,5-a]Pyrimidines
and Pyrazolo[3,4-b]Pyridines
C
hemistry of 2-Arylhy
e
drazonopr
o
r
panals vat Mohammed Abdel-Khalik,a Samia Michel Agamy,a Mohammed Hilmy Elnagdi*b
a
Department of Chemistry, Girls College for Arts, Science and Education, Ain Shams University, P.O. Box 11757 Heliopolis, Cairo, A.R.
Egypt
b
Department of Chemistry, Faculty of Science, Cairo University, Giza, A.R. Egypt
E-mail: shelmy@access.com.eg
Received 10 April 2001; revised 6 June 2001
cyclizes via loss of triphenylphosphine oxide. A similar
reaction sequence has recently been proposed to account
for the formation of dialkyl 1H-pyrrolizine-2,3-dicarbox-
ylates from the reaction of pyrrole-2-carbaldehyde with
Abstract: The reaction of 2-arylhydrazonopropanals 1a–d with
dimethyl acetylenedicarboxylate in anhydrous dichloromethane in
the presence of triphenylphosphine afforded 1,6-dihydropy-
ridazines 2a–d. Compound 1a reacted with dimethyl acetylenedi-
carboxylate in refluxing acetic acid yielding the corresponding dialkyl acetylenedicarboxylates.5 Several tautomeric
Michael adduct 4. Whereas compound 1d failed to react in acetic
acid with diphenylacetylene, its reaction with the same reagent in
structures seemed possible for the formed dihydropyr-
1
idazines. For example, the H NMR spectrum of 2b dis-
anhydrous dichloromethane in the presence of triphenylphosphine
played four singlets readily recognizable as arising from
afforded the Michael adduct 3. Compounds 2b–d reacted with hy-
the two methoxy (d = 3.64, 3.83), the NCH (d = 6.22) and
drazine hydrate affording the corresponding pyridazino[3,4-d]pyr-
the olefinic CH (d = 8.06) protons, along with the multip-
let in the aromatic region. The 13C NMR spectrum of 2b
revealed three sp3 carbons which can be assigned to the
two methoxy at d= 52.49, 53.04 and d = 54.93 for NCH,
thus excluding other potential tautomers. The structural
assignments made on the basis of the 1H and the 13C NMR
spectra of compound 2b were supported by measurement
of its IR spectra that exhibited an ester absorption at n =
1743, 1716 cm–1. Conjugation with the olefinic bond
shifts one of these bands to a lower frequency. However,
Michael adduct 3 was obtained from the reaction of 1d
with diphenylacetylene under the same reaction condi-
tion, and the adduct 4 was obtained from the reaction of
1a with dimethyl acetylenedicarboxylate in refluxing ace-
tic acid (Scheme 1). These adducts could not be further
cyclized into pyridazinone derivatives. Although synthe-
tic approaches to pyridazines are numerous and well ex-
plored,6–8 to our knowledge none of these approaches
would enable an easy access to pyridazine-5,6-dicarboxy-
late which are interesting starting materials for the rarely
described pyridazino[4,5-c]ring system.9
idazines 6b–d. 2-Arylhydrazonopropanals 1a,b reacted with 5-me-
thyl-1H-pyrazol-3-amine in ethanol yielding the corresponding
condensation products 8a,b, which cyclized to the 7-substituted 2-
methyl-6-phenylazopyrazolo[1,5-a]pyrimidines 9a,b and 4-substi-
tuted 3-methyl-5-phenylazopyrazolo[3,4-b]pyridines 10a,b on re-
fluxing in acetic acid. 2-Phenylhydrazonopropanal 1a reacted with
p-benzoquinone yielding the resorcinol derivative 12.
Key words: heterocycles, Michael addition, cyclization
The chemistry of 1,2,3-trione-2-arylhydrazones has re-
ceived considerable interest in the past.1 However, the
chemistry of structurally related 2-arylhydrazono-3-oxo-
propanals has received very limited interest.2–4 Some time
ago we described an efficient synthesis of 2-arylhydra-
zonopropanals and reported recently on their potential in
heterocyclic synthesis.2–4 In conjunction with this work
we describe here a facile one-pot synthesis of dialkyl 1,6-
dihydropyridazine-5,6-dicarboxylates in high yield utiliz-
ing the 2-arylhydrazonopropanals 1a–d as precursors for
this ring system. In addition, several new arylazopyra-
zolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyridines
have been synthesized utilizing 1a,b as starting materials.
Compounds 2a–d obtained appeared to be interesting pre-
cursors for the synthesis of condensed pyridazinones. To
demonstrate their potential, 2b–d were reacted with hy-
drazine hydrate to yield the dihydrazides 5b–d which cy-
clized into the pyridazinopyridazines 6b–d on refluxing in
dimethylformamide (Scheme 1).
Thus, compounds 1a–d reacted with dimethyl acetylene-
dicarboxylate in anhydrous dichloromethane and in the
presence of triphenylphosphine to yield the 1,6-dihydro-
pyridazines 2a–d (Scheme 1). Such products apparently
result from the initial addition of triphenylphosphine to
the acetylenic ester yielding a 1:1 adduct. This is followed
by attack of the hydrazone nitrogen on the formed vi-
nylphosphonium product affording an acyclic adduct that
Compounds 1a,b reacted with 5-methyl-1H-pyrazol-3-
amine (7) in refluxing ethanol to yield the corresponding
condensation products 8a,b. These could be smoothly
cyclized via loss of water yielding a mixture of the pyra-
zolo[1,5-a]pyrimidines 9 and pyrazolo[3,4-b]pyridines 10
1
(Scheme 2). The H NMR spectrum of the mixture dis-
Synthesis 2001, No. 12, 25 09 2001. Article Identifier:
1437-210X,E;2001,0,12,1861,1865,ftx,en;T02401SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
played six singlets, readily recognizable as arising from
two methyls at (d = 2.43 and 2.60 for 1.5 proton each), a

1862
M. M. Abdel-Khalik et al.
PAPER
Scheme 2
Scheme 3
Scheme 1
All melting points are uncorrected. IR spectra were recorded as KBr
pellets with a Pye Unicam SP 1100 spectrophotometer. H NMR
pyrazolyl 4-H proton at (d = 6.79 for 0.6 proton), pyridyl
2-H and pyrimidyl 4-H at (d = 8.50 and 9.03 for 0.4 proton
each), NH at (d = 13.55 for 0.4 proton) along with an aro-
matic multiplet at (d = 7.51–7.80 for a total of 10 protons).
It was thus concluded that the mixture is composed of
compounds 9 and 10 in the ratio of 3:2. Triturating the re-
action mixture with acetonitrile enabled complete dissolu-
tion of one of the two products. The remaining solid was
isolated and proved to be pyrazolo[3,4-b]pyridines 10.
Samples of pure 9 could not be obtained, as on evaporat-
ing the acetonitrile solution, a mixture of 9 and 10 was ob-
tained as 9 rearranged into 10 in most solvents. We
believe that 9 is the kinetic product whereas 10 is the
thermodynamic product. Rearrangement of some pyra-
zolo[1,5-a]pyrimidines into pyrazolo[3,4-b]pyridines has
once been observed earlier.10 It seems that the presence of
electron-attracting arylazo function in 9 increases the p-
deficiency of the ring moiety and thus facilitates ring-
opening process. The obtained arylazo derivatives have an
intense orange color and thus seem to be a new class of
arylazopyrazolo[3,4-b]pyridine dyes (Scheme 2).
1
spectra were recorded on a Varian EM-390 400 MHz spectrometer
in DMSO-d6 as solvent and TMS as internal standard; chemical
shifts are reported in d units (ppm). Mass spectra were measured at
70 eV using MS 30 and MS 9 (AEI) spectrometers. Microanalyses
were performed on a LECO CHNS-932 apparatus. Microanalytical
data were obtained from the Microanalytical Data Unit at Cairo
University. Compounds 1a–d were prepared following published
procedure.2
1,6-Dihydropyridazines 2a–d; General Procedure
To a magnetically stirred solution of Ph3P (2.62 g, 10 mmol) and
each of 2-arylhydrazonopropanals 1a–d (10 mmol) in CH2Cl2 (10
mL) was added dropwise a solution of dimethyl acetylenedicarbox-
ylate (1.42 g, 10 mmol) in CH2Cl2 (5 mL) at 0 °C over 15 min. The
mixture was left at r.t. and stirred for 24 h. The solvent was reduced
under vacuum and the solid product was filtered and crystallized
from dioxane.
Dimethyl 3-Benzoyl-1,6-dihydro-1-phenylpyridazine-5,6-
dicarboxylate (2a)
Yield: 3.47 g (92%); mp 109 °C.
IR (KBr): 1743, 1715 (ester CO), 1618 cm–1 (CO).
MS (EI): m/z (%) = 378 (M+).
Compound 1a reacted with p-benzoquinone 11 in acetic
acid in the presence of ferric chloride to yield the resorc-
inol derivative 12 in good yield (Scheme 3).
1H NMR (DMSO-d6): d = 3.65 (s, 3 H, OCH3), 3.84 (s, 3 H, OCH3),
6.24 (s, 1 H, NCH), 7.51–7.68 (m, 5 H, arom-H), 7. 74–7.81 (m, 5
H, arom-H), 8.11 (s, 1 H, 4-H).
In conclusion, the readily obtainable 2-arylhydrazonopro-
panals are valuable precursors for the synthesis of a vari-
ety of, otherwise not readily obtainable, heteroaromatics
of potential interest for biological evaluation.
Anal. Calcd for C21H18N2O5 (378.4): C, 66.66; H, 4.80; N, 7.40.
Found: C, 66.50; H, 4.93; N, 7.52.
Synthesis 2001, No. 12, 1861–1865 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Chemistry of 2-Arylhydrazonopropanals
1863
Dimethyl 1,6-Dihydro-3-(2-furoyl)-1-phenylpyridazine-5,6-
dicarboxylate (2b)
131.26, 131.30, 128.87, 128.70, 128.61, 128.50, 121.04, 118.55,
115.07, 112.35, 55.48 (OCH3).
Yield: 3.30 g (90%); mp 135 °C.
IR (KBr): 1743, 1716 (ester CO), 1620 cm–1 (CO).
Anal. Calcd for C28H22N2O4 (450.5): C, 74.65; H, 4.92; N, 6.22.
Found: C, 74.70; H, 4.85; N, 6.20.
MS (EI): m/z (%) = 368 (M+).
Dimethyl {1,3-Dioxo-1-phenyl-2-[2¢-(1¢-phenylhydrazono)pro-
pan-1-yl]}fumarate (4)
A solution of 1a (2.52 g, 10 mmol) and dimethyl acetylenedicarbox-
ylate (1.42 g, 10 mmol) in AcOH (20 mL) were refluxed for 3 h. Af-
ter cooling, the precipitate was filtered and recrystallized from
AcOH.
1H NMR (DMSO-d6): d = 3.65 (s, 3 H, OCH3), 3.84 (s, 3 H, OCH3),
6.25 (s, 1 H, NCH), 6.77–6.78 (m, 1 H, furyl-H), 7.29–7.33 (m, 1 H,
furyl-H), 7.49–7.65 (m, 6 H, 5 arom-H, 1 furyl-H), 8.11 (s, 1 H, 4-
H).
13C NMR (DMSO-d6): d = 174.06 (CO), 168.05 (ester CO), 164.13
(ester CO), 149.76 (C-3), 148.16, 144.15, 139.50, 129.45, 125.56,
121.76, 120.82, 118.27, 117.60, 112.55, 54.93 (NCH), 53.04, 52.49
(OCH3).
Yield: 3.19 g (82%); mp 138 °C.
IR (KBr): 1718 (ester CO), 1621 cm–1 (CO).
MS (EI): m/z (%) = 394 (M+).
1H NMR (DMSO-d6): d = 3.80 (s, 3 H, CO2CH3), 3.82 (s, 3 H,
CO2CH3), 7.17–7.96 (m, 10 H, arom-H), 5.82 (s, 1 H, vinyl-H),
10.03 (s, 1 H, CHO).
Anal. Calcd for C19H16N2O6 (368.3): C, 61.95; H, 4.38; N, 7.61.
Found: C, 61.91; H, 4.39; N, 7.80.
Dimethyl 1,6-Dihydro-1-phenyl-3-(2-thienoyl)pyridazine-5,6-
dicarboxylate (2c)
Yield: 3.64 g (95%); mp 110 °C.
IR (KBr): 1745, 1715 (ester CO), 1610 cm–1 (CO).
Anal. Calcd for C21H18N2O6 (394.4): C, 63.95; H, 4.60; N, 7.10.
Found: C, 63.88; H, 4.75; N, 7.20.
Dihydrazides 5b–d; General Procedure
MS (EI): m/z (%) = 384 (M+).
A mixture of each of the compounds 2b–d (10 mmol) in EtOH (30
mL) was treated with hydrazine hydrate (10 mL). The mixture was
heated under reflux for 1 h and allowed to cool to r.t. The solid prod-
uct was filtered and crystallized from dioxane.
1H NMR (DMSO-d6): d = 3.65 (s, 3 H, OCH3), 3.84 (s, 3 H, OCH3),
6.24 (s, 1 H, NCH), 7.24–7.32 (m, 2 H, thienyl-H), 7.47–8.02 (m, 6
H, 5 arom-H, 1 H thienyl-H), 8.11 (s, 1 H, 4-H).
13C NMR (DMSO-d6): d = 178.29 (CO), 168.00 (ester CO), 164.12
(ester CO), 144.06 (C-3), 139.66, 138.82, 136.12, 135.03,129.42,
127.87, 125.60, 120.93, 118.45, 117.83, 55.04 (NCH), 53.06 and
52.51 (OCH3).
1,6-Dihydro-3-(2-furoyl)-1-phenylpyridazine-5,6-dicarboxy-
dihydrazide (5b)
Yield: 3.31 g (90%); mp 235 °C.
IR (KBr): 3301, 3178 (NH, NH2), 1674, 1620 cm–1 (CO).
MS (EI): m/z (%) = 368 (M+).
Anal. Calcd for C19H16N2O5S (384.3): C, 59.37; H, 4.20; N, 7.29; S,
8.32. Found: C, 59.47; H, 4.38; N, 7.31; S, 8.16.
1H NMR (DMSO-d6): d = 5.98 (s, 1 H, NCH), 6.75–6.79 (m, 1 H,
furyl-H), 7.22–8.01 (m, 11 H, 2 H furyl-H, 5 H arom-H, 4 H 2 NH2),
8.10 (s, 1 H, H-4), 9.14 (br s, 1 H, NH), 10.04 (br s, 1 H, NH).
Dimethyl 1,6-Dihydro-3-(2-furoyl)-1-(4-methoxyphenyl)pyri-
dazine-5,6-dicarboxylate (2d)
Yield: 3.74 g (94%); mp 138 °C.
Anal. Calcd for C17H16N6O4 (368.4): C, 55.43; H, 4.38; N, 22.82.
Found: C, 55.40; H, 4.43; N, 22.94.
IR (KBr): 1744, 1715 (ester CO), 1615 cm–1 (CO).
MS (EI): m/z (%) = 398 (M+).
1H NMR (DMSO-d6): d = 3.32 (s, 3 H, OCH3), 3.80 (s, 3 H,
CO2CH3), 3.82 (s, 3 H, CO2CH3), 6.20 (s, 1 H, NCH), 6.75–6.76 (m,
1 H, furyl-H), 7.05–7.07 (m, 2 H, furyl-H), 7.54–7.75 (m, 4 H,
arom-H), 8.09 (s, 1 H, 4-H).
1,6-Dihydro-1-phenyl-3-(2-thienoyl)pyridazine-5,6-dicarboxy-
dihydrazide (5c)
Yield: 3.64 g (95%); mp 220 °C.
IR (KBr): 3309, 3178 (NH, NH2), 1674, 1604 cm–1 (CO).
MS (EI): m/z (%) = 384 (M+).
Anal. Calcd for C20H18N2O7 (398.4): C, 60.30; H, 4.55; N, 7.03.
Found: C, 60.37; H, 4.55; N, 7.20.
1H NMR (DMSO-d6): d = 5.97 (s, 1 H, NCH), 7.15–7.44 (m, 2 H,
thienyl-H), 7.48–7.99 (m, 8 H, 1 H thienyl-H, 5 H arom-H, 2 H
NH2), 8.06–8.07 (m, 2 H, NH2), 8.13 (s, 1 H, H-4), 9.14 (br s, 1 H,
NH), 10.05 (br s, 1 H, NH).
3-(2-Furyl)-2-(N-diphenylethyleno-4-methoxyphenylhydrazo-
no)-3-oxopropanal (3)
To a magnetically stirred solution of Ph3P (2,62 g, 10 mmol) and
2-phenylhydrazonopropanal 1a (2.52 g, 10 mmol) in CH2Cl2 (10
mL) was added dropwise a solution of diphenylacetylene (1.78 g,
10 mmol) in CH2Cl2 (5 mL) at 0 °C over 15 min. The mixture was
left at r.t. and stirred for 24 h. The solvent was reduced under vacu-
um and the solid product was filtered and crystallized from dioxane.
Anal. Calcd for C17H16N6O3S (384.4): C, 53.12; H, 4.20; N, 21.87;
S, 8.32. Found: C, 53.32; H, 4.18; N, 21.80; S, 8.12.
1,6-Dihydro-3-(2-furoyl)-1-(4-methoxyphenyl)pyridazine-5,6-
dicarboxydihydrazide (5d)
Yield: 3.58 g (90%); mp 240 °C.
IR (KBr): 3304, 3178 (NH, NH2), 1674, 1618 cm–1 (CO).
MS (EI): m/z (%) = 398 (M+).
1H NMR (DMSO-d6): d = 3.80 (s, 3 H, OCH3), 5.95 (s, 1 H, N-CH),
6.73–6.79 (m, 1 H, furyl-H), 7.02–7.07 (m, 2 H, furyl-H), 7.53–7.98
(m, 8 H, 4 H arom-H, 4 H 2 NH2), 8.10 (s, 1 H, H-4), 9.14 (br s, 1
H, NH), 10.05 (br s, 1 H, NH).
Yield: 4.05 g (90%); mp 103 °C.
IR (KBr): 1639, 1619 cm–1 (CO).
MS (EI): m/z (%) = 450 (M+).
1H NMR (DMSO-d6): d = 3.77 (s, 3 H, OCH3), 6.73–6.74 (m, 1 H,
furyl-H), 7.01–7.04 (m, 2 H, furyl-H), 7.23–7.25 (m, 5 H, arom-H),
7.36–7.46 (m, 5 H, arom-H), 7.47–7.48 (m, 2 H, arom-H), 7.52–
7.55 (m, 2 H, arom-H), 5.31 (s, 1 H, vinyl-H), 9.91 (s, 1 H, CHO).
Anal. Calcd for C18H18N6O5 (398.4): C, 54.27; H, 4.55; N, 21.10.
Found: C, 54.40; H, 4.56; N, 21.00.
13C NMR (DMSO-d6): d = 187.09 (CHO), 176.55 (CO), 158.02 (C-
2), 149.96, 147.51, 136.82, 136.67, 136.67, 134.77, 133.33, 133.07,
Synthesis 2001, No. 12, 1861–1865 ISSN 0039-7881 © Thieme Stuttgart · New York

1864
M. M. Abdel-Khalik et al.
PAPER
Pyridazinopyridazines 6b–d; General Procedure
Each of the hydrazide 5b–d (10 mmol) in DMF (10 mL) was re-
fluxed for 1 h, then poured onto ice-water . The solid product was
filtered and crystallized from DMF.
1H NMR (DMSO-d6): d = 2.28 (s, 3 H, CH3), 6.38 (s, 1 H, pyrazolyl-
H), 6.80–6.81 (m, 1 H, furyl-H), 7.23–7.26 (m, 2 H, furyl-H), 7.50–
7.62 (m, 3 H, arom-H), 7.92–8.09 (m, 2 H, arom-H), 8.95 (s, 1 H,
amidine-H), 12.69 (br s, 1 H, NH), 15.42 (br s, 1 H, NH).
Anal. Calcd C17H15N5O2 (321.3): C, 63.54; H, 4.70; N, 21.80.
Found: C, 63.71; H, 4.66; N, 21.98.
3-(2-Furoyl)-8-hydrazino-1-phenyl-1,5,6,8a-tetrahydropyrida-
zino[3,4-d]pyridazin-5-one (6b)
Yield: 3.15 g (90%); mp 212 °C.
IR (KBr): 3410, 3330, 2935 (NH, NH2), 1680, 1620 cm–1 (CO).
MS (EI): m/z (%) = 350 (M+).
1H NMR (DMSO-d6): d = 5.93 (s, 1 H, NCH), 6.75–6.79 (m, 1 H,
furyl-H), 7.28–8.06 (m, 9 H, 2 H furyl-H, 5 H arom-H, 2 H NH2),
8.10 (s, 1 H, 4-H), 9.18 (br s, 1 H, NH), 10.00 (br s, 1 H, NH).
Pyrazolo[3,4-b]pyridines 10a,b; General Procedure
Each of the compounds 8a,b (10 mmol) in AcOH (10 mL) was re-
fluxed for 1h and then allowed to cool to r.t. The solid product ob-
tained was filtered and triturated with MeCN. The filtrate was
concentrated under vacuum and the residue was crystallized from
dioxane to afford compound 10 in pure form.
3-Methyl-4-phenyl-5-phenylazo-1H-pyrazolo[3,4-b]pyridine
(10a)
Yield: 1.12 g (36%); mp 180 °C.
Anal. Calcd for C17H14N6O3 (350.3): C, 58.28; H, 4.03; N, 23.99.
Found: C, 58.10; H, 4.09; N, 24.12.
IR (KBr): 3180 cm–1 (NH).
MS (EI): m/z (%) = 313 (M+).
1H NMR (DMSO-d6): d = 2.43 (s, 3 H, CH3), 7.51–7.77 (m, 10 H,
arom-H), 8.50 (s, 1 H, pyridyl-H), 13.55 (s, 1 H, NH).
8-Hydrazino-1-phenyl-1,5,6,8a-tetrahydro-3-(2-thienoyl)pyri-
dazino[3,4-d]pyridazin-5-one (6c)
Yield: 3.47 g (95%); mp 221 °C.
IR (KBr): 3420, 3330, 2918 (NH, NH2), 1679, 1614 cm–1 (CO).
MS (EI): m/z (%) = 366 (M+).
1H NMR (DMSO-d6): d = 5.97 (s, 1 H, NCH), 7.15–7.44 (m, 2 H,
thienyl-H), 7.32–8.08 (m, 10 H, 1 H thienyl-H, 5 H arom-H, 2 H
NH2), 8.10 (s, 1 H, 4-H), 9.16 (br s, 1 H, NH), 10.11 (br s, 1 H, NH).
Anal. Calcd for C19H15N5 (313.4): C, 72.82; H, 4.83; N, 22.35.
Found: C, 72.86; H, 4.67; N, 22.10.
4-(2-Furyl)-3-methyl-5-phenylazo-1H-pyrazolo[3,4-b]pyridine
(10b)
Anal. Calcd for C17H14N6O2S (366.3): C, 55.73; H, 3.85; N, 22.94;
S, 8.73. Found: C, 55.84; H, 4.08; N, 23.81; S, 8.62.
Yield: 0.96 g (32%); mp 277 °C.
IR (KBr): 3170 cm–1 (NH).
MS (EI): m/z (%) = 303 (M+).
1H NMR (DMSO-d6): d = 2.51 (s, 3 H, CH3), 6.73–6.75 (m, 1 H, fu-
ryl-H), 7.15–7.16 (m, 1 H, furyl-H), 7.61–7.66 (m, 3 H, 2 H arom-
H, 1 H furyl-H), 7.75–7.98 (m, 3 H, arom-H), 8.43 (s, 1 H, pyridyl-
H).
3-(2-Furoyl)-8-hydrazino-1-(4-methoxyphenyl)-1,5,6,8a-
tetrahydropyridazino[3,4-d]pyridazin-5-one (6d)
Yield: 3.34 g (88%); mp 215 °C.
IR (KBr): 3420, 3332, 2939 (NH, NH2), 1681, 1620 cm–1 (CO).
MS (EI): m/z (%) = 380 (M+).
1H NMR (DMSO-d6): d = 3.80 (s, 3 H, OCH3), 5.92 (s, 1 H, N-CH),
6.76–6.77 (m, 1 H, furyl-H), 7.04–7.07 (m, 2 H, furyl-H), 7.42–7.74
(m, 4 H, 2 H arom-H, 2 H NH2), 7.57–7.59 (m, 2 H, arom-H), 8.08
(s, 1 H, 4-H), 9.10 (br s, 1 H, NH), 10.00 (br s, 1 H, NH).
Anal. Calcd for C17H13N5O (303.3): C, 67.31; H, 4.32; N, 23.09.
Found: C, 67.29; H, 4.21; N, 22.90.
3-Oxo-2-[N-(2,5-dihydroxyphenyl)-N-phenylhydrazono]-3-
phenylpropanal (12)
Compound 1a (2.52 g, 10 mmol) in AcOH (30 mL) was treated with
p-benzoquinone (1.08 g, 10 mmol). The mixture was heated under
reflux for 3 h and allowed to cool to r.t. The solid product was fil-
tered and crystallized from dioxane.
Anal. Calcd for C18H16N6O4 (380.4): C, 56.84; H, 4.24; N, 22.10.
Found: C, 56.92; H, 4.12; N, 22.00.
Condensation Products 8a,b; General Procedure
Each of the compounds 1a,b (10 mmol) in EtOH (30 mL) was treat-
ed with 5-methyl-1H-pyrazol-3-amine (0.97 g, 10 mmol). The mix-
ture was heated under reflux for 1 h and allowed to cool to r.t. The
solid product was filtered and crystallized from dioxane.
Yield: 2.88 g (80%); mp 230 °C.
IR (KBr): 3330 br (OH), 1635, 1621 cm–1 (CO).
MS (EI): m/z (%) = 360 (M+).
1H NMR (DMSO-d6): d = 7.17–7.89 (m, 13 H, arom-H), 10.01 (s, 1
H, CHO), 13.26 (br s, 1 H, OH), 14.25 (br s, 1 H, OH).
(1-Phenyl-2-phenylhydrazonopropane)-3-(3¢-methyl-1¢H-pyra-
zol-5¢-yl)imine-1-one (8a)
Yield: 2.81 g (85%); mp 196 °C.
IR (KBr): 3170 (NH), 1643 cm–1 (CO).
MS (EI): m/z (%) = 331 (M+).
Anal. Calcd for C21H16N2O4 (360.4): C, 69.99; H, 4.48; N, 7.77.
Found: C, 69.92; H, 4.44; N, 7.83.
1H NMR (DMSO-d6): d = 2.28 (s, 3 H, CH3), 6.38 (s, 1 H, pyrazolyl-
H), 7.17–7.62 (m, 8 H, arom-H), 7.87–7.90 (m, 2 H, arom-H), 9.03
(s, 1 H, amidine-H), 12.69 (br s, 1 H, NH), 15.40 (br s, 1 H, NH).
References
(1) El-Sakka, I. A. J. Chem. Res. (S) 1996, 434.
(2) Al-Omran, F.; Abdel-Khalik, M. M.; Abou El-Khair, A.;
Elnagdi, M. H. Synthesis 1997, 91.
Anal. Calcd for C19H17N5O (331.4): C, 68.86; H, 5.17; N, 21.14.
Found: C, 68.92; H, 5.14; N, 20.98.
(3) Behbehani, H.; Abdel-Khalik, M. M.; Elnagdi, M. H. Org.
Prep. Proced. Int. 1999, 31, 551.
(4) Abdel-Khalik, M. M.; Agamy, S. M.; Elnagdi, M. H. Z.
Naturforsch. 2000, 55b, 1211.
1-(2-Furyl)-2-phenylhydrazonopropane)-3-(3¢-methyl-1¢H-
pyrazol-5¢-yl)imine-1-one (8b)
Yield: 2.79 g (87%); mp 202 °C.
(5) Yavari, I.; Djahaniani, H.; Maghsoodlou, M. T.; Hazeri, N.
J. Chem. Res., Synop. 1999, 382.
IR (KBr): 3150 (NH), 1620 cm–1 (CO).
MS (EI): m/z (%) = 321 (M+).
Synthesis 2001, No. 12, 1861–1865 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
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Synthesis 2001, No. 12, 1861–1865 ISSN 0039-7881 © Thieme Stuttgart · New York