Dicyanomethylene compounds and heterocyclization of substituted carbohydrazides

Article abstract of DOI:10.1002/jhet.115

(Chemical Equation Presented) (1,3-Dioxo-2,3-dihydro-1H-inden-2-ylidene) propanedinitrile (2, in dimethylformamide solution), 3-(dicyanomethylene)-2- indolone (3, in ethanol/piperidine solution) act on substituted carbohydrazides 1a-e forming the derivati

Full text of DOI:10.1002/jhet.115

616
Dicyanomethylene Compounds and Heterocyclization of
Substituted Carbohydrazides
Vol 46
Alaa A. Hassan,* Yusria R. Ibrahim, and Ahmed M. Shawky
Chemistry Department, Minia University, 61519-El-Minia, A. R. Egypt
*E-mail: alaahassan2001@yahoo.com
Received March 12, 2008
DOI 10.1002/jhet.115
Published online 2 July 2009 in Wiley InterScience (www.interscience.wiley.com).
(1,3-Dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile (2, in dimethylformamide solution), 3-
(dicyanomethylene)-2-indolone (3, in ethanol/piperidine solution) act on substituted carbohydrazides
1a–e forming the derivatives of oxadiazolylideneindene-1,3-diones 4a–e, spiro(indene-2,20-oxadiazole)-
1,3-dione 5a–e, cyloxoindenopyrazolecarbonitriles 6a–e, spiro(indoline-3,20-oxadiazol)-2-ones 11a–e,
and acylpyrazoloindoles 13a–e. Rational for these conversions involving the nucleophilic addition on
the dicyanomethylene carbon atom are presented.
J. Heterocyclic Chem., 46, 616 (2009).
INTRODUCTION
Recently, we have reported an efficient transformation
of substituted acylhydrazinecarbothioamides with 2 and
3 into oxoindenopyrrolylidenehydrazide, thiazoloindolyl-
idenehydrazide, and pyrroloindolylidenehyrazide deriva-
tives [24].
In organic p-acceptors containing dicyanomethylene
groups such as ethenetetracarbonitrile and (1,3-dioxo-
2,3-dihydro-1H-inden-2-ylidene)propanedinitrile (2), the
nitrile groups can be substituted by the nucleophilic
nitrogen atom of primary aromatic [1–3] and secondary
aliphatic amines [4,5]. Tertiary aromatic amines (like
N,N-dimethylaniline) are prone to attack to the C¼¼C
double bond of 2 with their para-position, followed by
release of HCN [3,6–10]. By reaction of acceptor 2 with
tertiary cyclic amines, one can generate the iminium
ions and formation of the a-cyanated amines [11]. Addi-
tionally, the reaction of 2 with arylazoaminopyrazoles
[12,13], 2-mercaptobenzazoles [14], thiocarbohydrazide,
and thiocarbazones [15] as well as N-arylisoindolines
[16] have been reported. Closely analogous 3-(dicyano-
methylene)-2-indolone (3) [17] which is a ylidene malo-
nonitrile like 2 reacted with thiobarbituric acid [18],
S,S- and N,S-acetals [19], cyclohexanedione [20], and
another active methylene systems to give spirohetero-
cyclic compounds [21,22]. The reaction of N,N0-diaryla-
cetamidines with 2 afforded indenoazepine-6-ones [23].
In contrast, spiro[2,3-dihydro-indol-3,40-pyridino]-50-car-
bonitriles were obtained from the reaction of N,N0-diary-
lacetamidines with 3 [23].
These intriguing transformations led us to investigate
the reaction of carbohydrazides 1a–e bearing a selection
of aromatic and heterocyclic substitutions with acceptor
systems 2 and 3 (Fig. 1).
RESULTS AND DISCUSSION
Dimethylformamide solutions of 2 and substituted car-
bohydrazides 1a–e in a molar ratio of 2:1 were stirred at
room temperature for 48 h. Concentration of the reaction
mixture yielded reddish brown crystals from 2-(5-substi-
tuted-1,3,4-oxadiazol-2(3H)-ylidene)-1H-indene-1,3-(2H)-
diones 4a–e (51–57%). The remaining soluble materials
were subjected to preparative layer chromatography to
give 50-substituted spiro(indene-2,20-[1,3,4]-oxadiazole)-
1,3-dione 5a–e (13–17%) and 1-acyl-4-oxo-indeno[1,2-
c]pyrazole-3-carbonitriles 6a–e (11–15%).
The structures of 4a–e were delineated from their
spectroscopic properties and gross compositions. The
products 4a–e resulted from 1a–e were found to be
C
V
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Dicyanomethylene Compounds and Heterocyclization of Substituted Carbohydrazides
617
Compounds 5a–e show sharp absorptions characteris-
tic of carbonyl group at 1725–1710, NH group at 3330–
3315, C¼¼N group at 1630–1620 cmꢀ1, as well as
1
CAOAC group 1095–1080 cmꢀ1. The H NMR spec-
trum (DMSO-d6) of 5a clearly shows the presence of
oxadiazole-NH at (d ¼ 12.55 ppm) and phenyl protons
at (d ¼ 7.34–8.12 ppm). The 13C NMR of 5a shows sig-
nals at d ¼ 103.67 for (spiro-C-2,20), 156.47 (C-5), and
187.42 (C-1,3), in addition to aryl carbons. The molecu-
lar formulae of compounds 5a–e were supported by ele-
mental analysis and mass spectra, which gave the
expected molecular ion peaks. The alternative structure
8 (Scheme 2) based on the same elemental composition
Figure 1. Substituted carbohydrazides and some electron acceptors.
1
could be eliminated according to ir, H NMR and 13C
NMR spectral data.
formed by reacting one molecule of 1a–e and one mole-
cule of 2 via loss two molecules of HCN. The molecular
ions in their EI-mass spectra confirm the molecular
masses and the gross compositions. Furthermore, the
following common features of the fragmentation patterns
lend support to the assigned structures: Loss of RCO
giving rise to the ion m/z ¼ 185 common in the spectra
of all five compounds. The resulting fragment ions
undergo loss of 28 a.m.u. (dinitrogen or CO group). The
ir spectra show characteristic absorptions for NH group
in range 3330 to 3355 and carbonyl absorption at 1705–
1720 cmꢀ1 as expected for indane-1,3-dione ring sys-
tem. Strong bands around 1080–1095 have to be
assigned to CAOAC group [25].
The results of combustion analysis and spectroscopic
data suggested the presence of acyloxoindenopyrazole
derivatives 6a–e as one of the products from the reac-
tion between 1a–e and 2. The gross formula,
C20H10N4O2, 6e was confirmed by the mass spectrum,
which exhibited the molecular ion at m/z 338 (26%) and
the fragmentation pattern at 312, 284, 144, 140, 104, 91,
77, and 65. The ir spectrum showed absorptions at 3365
1
(NH), 2220 (CN), and 1710, 1665 (CO). The H NMR
spectrum of 6e displayed one broad singlet at 11.69
ppm for 1H (indole-NH) and another sharp singlet at
6.64 due to indole-CH in addition to the aromatic pro-
tons. In its 13C NMR spectrum, C-3 and C-4 resonate at
d ¼ 121.69 and 189.31 ppm, respectively; further peaks
are at d ¼ 99.91 ppm (indole-CH), 105.06 (C-3a),
149.76 (C-8a), 167.72 acyl-CO, and cyano group at
118.11 ppm.
1
The H NMR spectra show the presence of a broad
signal for 1H at d ¼ 12.57–12.64 ppm due to oxadia-
zole-NH, and additionally, the expected signals for R
groups. In the 13C NMR spectrum of 4b, the carbonyl
groups resonate at 187.34 ppm. Further peaks at 91.64
(indene-C-2) [16], 154.55 (oxadiazole-C-5), and 174.26
(oxadiazole-C-2) lend support to the structures assigned
to 4a–e (Scheme 1).
Scheme 2
Scheme 1
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618
A. A. Hassan, Y. R. Ibrahim, and A. M. Shawky
Vol 46
Compound 10 (Scheme 2) could be ruled out, owing
of 11e (probably indol-2-carbonyl). The ir spectrum
showed absorption at 3325–3370 (NH’s), 1720 (CO),
to the presence of acyl-CO signals in the 13C NMR
spectra. A rational for the formation of the products 4–6
is presented in scheme 2. The carbohydrazides 1a–e and
2 give the neutral adduct 7. Elimination of a molecule
of malononitrile afforded compounds 5, whereas elimi-
nation two molecules of HCN gave compounds 4. Elimi-
nation one molecule of HCN from the adduct 7 afforded
the intermediate 9 followed by elimination a molecule
of H2O to give oxoindenopyrazole derivatives 6.
1
1090 (C-O-C). The H NMR spectrum of 11e showed
the presence of three broad signals with the ratio 1:1:1
centered at 9.81, 11.75, and 12.38 due to indolinone-
NH, indole-NH, and oxadiazole -NH, respectively.
Indole-CH resonate at 6.57 ppm in addition to the aro-
matic protons. Signals around 93.66 (spiro C-3 ¼ C-20),
101.96 (indole-CH), 154.84 (C-50), and 177.90 (CO) in
addition to the aromatic carbons.
Reflux of one mole of 1a–e with two equivalents of
3-(dicyanomethylene)-2-indolone (3) in ethanol/piperi-
dine resulted in pink coloration of the solution, which
later became yellowish brown. The residue remaining
after concentration was subjected to preparative layer
chromatography to give 50-substituted-spiro[indoline-
3,20-1,3,4-oxadiazol]-2-one 11a–e (64–71%) and 1-(sub-
stituted-2-carbonyl)-1,2-dihydro-pyrazolo[3,4-b]-indole-
3-carbonitrile 13a–e (21–26%) (Scheme 3).
Compounds 11a–e. The EI-mass spectra of 11a–e
are characterized by molecular ions of low intensity and
loss of 28 a.m.u. (may be dinitrogen or carbonyl group)
followed by loss of 144 a.m.u. from the molecular ion
The alternative structure 12 was ruled out based on
mp, ir, 1H NMR and 13C NMR spectral data. It has
been reported that 1a and isatine were ball-milled at
room temperature for 3 h to give 12a [26] after drying
at 0.01 bar at 80ꢁC. Also, 12a was obtained during the
reaction of 1a with isatine under reflux in MeOH [27].
Recently, it has been reported that under acetylating
condition, isatine-3-acylhydrazones were transformed
into selectively acylated derivatives and into the corre-
sponding 3-acetyl-1,3,4-oxadiazolines [28].
Compounds 13a–e. Substituted carbonyl-1,2-dihydro-
pyrazolo[3,4-b]indole-3-carbonitrile 13a–e (21–26%),
the ir spectrum of 13b shown absorption bands charac-
teristic of NH group at 3395 cmꢀ1, strong cyano group
1
at 2215, and one carbonyl absorption at 1660 cmꢀ1. H
Scheme 3
NMR spectrum of 13b clearly supports the presence of
broad signals centered at 11.98 ppm due to pyrazole-
NH, aromatic, and thiophene protons were also
observed. The 13C NMR spectrum of 13b exhibited a
signal at d ¼ 169.64 for carbonyl group, 118.24 (CN),
102.36 (C-3a), and 148.66 (C-8a). Therefore, we will
concentrate on the interplay between the formation of
the products 13a–e and alternative structure 14. The a
priori possible isomeric structures 14 were ruled out on
1
the basis of H NMR and 13C NMR, which clearly sup-
port the presence of pyrazole-NH [29] and hydrazide-
CO groups. Also, the spectral data showed the absence
of indolone-CO, indolone-NH, and spiro-carbons [30].
EXPERIMENTAL
Mps were determined with a Gallenkamp melting point ap-
paratus and were uncorected. The ir spectra were recorded
with a Shimadzu 408 instrument using potassium bromide pel-
lets. Five hundred Megahertz 1H and 125 MHz 13C NMR
spectra were recorded on a Bruker AVANCE DRX 500 spec-
trometer. Chemical shifts are expressed as d (ppm) with refer-
ence to tetramethylsilane as internal standard, br ¼ broad, s
¼singlet, and m ¼ multiplet. 13C assignments (q ¼ quaternary
carbon atoms) were made with the aid DEPT 135/90 spectra.
The mass spectra (70 eV, electron impact mode) were
recorded on Varian MAT CH-7 instrument. Elemental analyses
were carried out at the Microanalytical Center, Cairo Univer-
sity, Egypt. Preparative layer chromatography (PLC) was
made using 48 cm ꢂ 20 cm glass plates covered with slurry
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July 2009
Dicyanomethylene Compounds and Heterocyclization of Substituted Carbohydrazides
619
applied and air dried 1.0 mm thick layers of Merck silica gel
Pf254. Zones were detected by indicator fluorescence quenching
upon 254 nm exposure, removed from plates, and extracted
with cold acetone
(C-5), 174.16 (C-2), 187.83 (CO); ms m/z: 280 (Mþ, 41), 185
(37), 104 (77), 95 (100), 76 (56), 65 (66). Anal. Calcd. for
C15H8N2O4: C, 64.29; H, 2.88; N, 10.00. Found: C, 64.11; H,
3.04; N, 9.83.
Starting materials. Substituted carbohydrazides 1a–e were
prepared according to published procedures [31–36], as were
2-thiophene carbo-hydrazide (1b), mp 135–137ꢁC (lit. [31]
134–136ꢁC); furan-2-carbohydrazide (1c), mp 77–79 (lit. [32]
78ꢁC); 2-pyridine carbohydrazide (1d), mp 136–138ꢁC (lit.
[33] 137ꢁC); indole-2-carbohydrazide (1e), mp 243–245ꢁC (lit.
[34–36] 246ꢁC) and phenyl carbohydrazide (1a) (Aldrich) was
used as received. 2-(1,3-Dioxo-2,3-dihydro-1H-inden-2-ylide-
2-(5-(Pyridine-2-yl)-1,3,4-oxadiazol-2-(3H)-ylidene)-1H-in-
dene-1,3-(2H)-dione (4d). This compound was obtained as
reddish brown crystals (methanol), mp 262–264ꢁC; ir: NH
3355, CO 1705, C¼¼N 1630, Aryl and C¼¼C 1610, CAOAC
1095; 1H NMR: d 7.54–8.43 (m, 8H, ArAH and pyridine-H),
12.57 (br, 1H, oxadiazole-NH); 13C NMR: d 91.48 (indene-C-
2), 126.33, 126.84, 126.87, 136.33 (ArACH and pyridine-CH),
141.44, 143.59 (ArAC), 147.14, 149.34 (pyridine-C-2, C-6),
155.12 (C-5), 174.32 (C-2), 187.66 (CO); ms m/z: 291 (Mþ,
24), 185 (29), 106 (58), 104 (67), 76 (66), 65 (100). Anal.
Calcd. for C16H9N3O3: C, 65.98; H, 3.11; N, 14.43. Found: C,
66.17; H, 2.98; N, 14.27.
2-(5-(1H-Indol-2-yl)-1,3,4-oxadiazol-2-(3H)-ylidene)-1H-
indene-1,3-(2H)-dione (4e). This compound was obtained as
reddish brown crystals (methanol), mp 291–293ꢁC; ir: NH
3385–3340, CO 1720, C¼¼N 1625, Aryl and C¼¼C 1590,
CAOAC 1095; 1H NMR: d 6.58 (s, 1H, indole-CH), 7.09–
8.13 (m, 8H, ArAH), 11.69 (br, 1H, indole-NH), 12.61 (br,
1H, oxadiazole-NH); 13C NMR: d 91.76 (indene-C-2), 102.12
(indole-CH), 125.23 (indole-C-2), 126.27, 127.96, 135.78,
138.26 (ArACH), 140.22, 141.38, 142.57, 143.81 (ArAC),
155.06 (C-5), 174.47 (C-2), 187.71 (CO); ms m/z: 329 (Mþ,
39), 225 (23), 185 (34), 144 (41), 104 (74), 91 (57), 76 (100),
65 (69). Anal. Calcd. for C19H11N3O3: C, 69.30; H, 3.37; N,
12.76. Found: C, 69.13; H, 3.25; N, 12.95.
50-Phenyl-30H-spiro(indene-2,20-[1,3,4]oxadiazole)-1,3-dione
(5a). This compound was obtained as yellow crystals (etha-
nol), mp 206–208ꢁC; ir: NH 3325, CO 1715, C¼¼N 1625,
ArAC¼¼C 1595, CAOAC 1090; 1H NMR: d 7.34–8.12 (m,
9H, ArAH), 12.55 (br, 1H, oxadiazole-NH); 13C NMR: d
103.67 (C-2,20), 126.27, 126.56, 128.31, 129.26, 130.44
(ArACH), 132.84, 134.71 (ArAC), 156.47 (C-50), 187.42 (C-
1,3); ms m/z: 278 (Mþ, 34), 250 (49), 145 (67), 105 (89), 104
(59), 77 (100), 65 (71); Anal. Calcd. for C16H10N2O3: C,
69.06; H, 3.62; N, 10.07. Found: C, 68.84; H, 3.73; N, 9.88.
50-(Thiophen-2-yl)-30H-spiro(indene-2,20-[1,3,4]oxadi-azole)-
1,3-dione (5b). This compound was obtained as yellow crystals
(ethanol), mp 227–228ꢁC; ir: NH 3315, CO 1710, C¼¼N 1620,
ArAC¼¼C 1600, CAOAC 1080; 1H NMR: d 7.23–8.15 (m,
7H, ArAH and thiophene-H), 12.51 (br, 1H, oxadiazole-NH);
13C NMR: d 103.69 (C-2,20), 126.36, 126.72, 127.94, 128.66,
130.46 (ArACH and thiophene-CH), 132.82, 134.66 (ArAC
and thiophene-C), 156.39 (C-50), 187.47 (C-1,3); ms m/z: 284
(Mþ, 41), 256 (17), 145 (46), 111 (100), 104 (73), 77 (64), 65
(55); Anal. Calcd. for C14H8N2O3S: C, 59.15; H, 2.84; N,
9.85; S, 11.28. Found: C, 58.89; H, 2.92; N, 10.03; S, 11.05.
50-(Furan-2-yl)-30H-spiro(indene-2,20-[1,3,4]oxadiazole)-1,3-
dione (5c). This compound was obtained as yellow crystals
(acetonitrile), mp 189–190ꢁC; ir: NH 3320, CO 1710, C¼¼N
1625, CAOAC 1100, 1080; 1H NMR: d 7.26–8.15 (m, 7H,
ArAH and furan-H), 12.54 (br, 1H, oxadiazole-NH); 13C
NMR: d 103.71 (C-2,20), 125.97, 126.43, 126.42, 130.34
(ArACH and furan-CH), 134.26 (ArAC), 140.96, 141.88
(furan-C-2, C-5), 156.47 (C-50), 187.55 (C-1,3); ms m/z: 268
(Mþ, 33), 240 (21), 145 (28), 104 (67), 95 (81), 77 (100), 65
(49); Anal. Calcd. for C14H8N2O4: C, 62.69; H, 3.01; N,
10.44. Found: C, 62.46; H, 2.94; N, 10.67.
ne)pro-panedinitrile(dicyanomethyleneindane-1,3-dione)
(2)
was prepared according chatterjee [37], yellow crystals, mp
282–284ꢁC with decomposition, black preheated to 260ꢁC (lit.
[37] 280–285ꢁC with decomp.). 3-(Dicyanomethylene)-2-indo-
lone (3) was prepared according to Fatiadi [17], brick-red nee-
dles, mp 235–236ꢁC (lit. [17] 235–237ꢁC).
Reactions of carbohydrazides 1a–e with (2). To a solution
of 2 (416 mg, 2.0 mmol) in dry dimethylformamide (DMF)
(15 mL), a solution of 1a–e (1.0 mmol each) in 5 mL of DMF
was added drop wise over 5 min at room temperature with
stirring and admission of air for 3 h and left standing for 48 h
at room temperature. Reddish brown crystals were precipitated,
filtered, and washed with small amount of cold ethanol, which
contains 2-(5-substituted-1,3,4-oxadiazol-2-(3H)-ylidene)-1H-
indene-1,3-(2H)-diones (4a–e). The filtration was concentrated
to dryness and dissolved in a few mL of acetone and subjected
to PLC using toluene/ethyl acetate (2:1) to afford two zones.
The fastest migrating fraction contained compounds 5a–e and
the slowest migrating zone contained 6a–e.
2-(5-Phenyl-1,3,4-oxadiazol-2-(3H)-ylidene)-1H-indene-1,3-
(2H)-dione (4a). This compound was obtained as reddish
brown crystals (acetonitrile), mp 247–249ꢁC; ir: NH 3340, CO
1710, C¼¼N 1630, Aryl and C¼¼C 1605, CAOAC 1085 cmꢀ1
.
1H NMR: d 7.38–8.18 (m, 9H, ArAH), 12.64 (br, 1H, oxadia-
zole-NH); 13C NMR: d 91.57 (indene-C-2), 126.31, 128.41,
129.67, 135.86, 138.17 (ArACH), 141.27, 143.67 (ArAC),
154.67 (C-5), 174.34 (C-2), 187.38 (CO); ms: m/z 290 (Mþ,
31), 185 (52), 153 (13), 105 (100), 104 (76), 77 (68), 65 (55).
Anal. Calcd. for C17H10N2O3: C, 70.34; H, 3.47; N, 9.65.
Found: C, 70.57; H, 3.39; N, 9.73.
2-(5-(Thiophen-2-yl)-1,3,4-oxadiazol-2-(3H)-ylidene)-1H-
indene-1,3-(2H)-dione (4b). This compound was obtained as
reddish brown crystals (acetonitrile), mp 270–272ꢁC; ir: NH
3330, CO 1715, C¼¼N 1625, Aryl and C¼¼C 1600, CAOAC
1
1080; H NMR: d 7.19–8.16 (m, 7H, ArAH and thiophene-H),
12.62 (br, 1H, oxadiazole-NH); 13C NMR: d 91.64 (indene-C-
2), 126.14, 127.49, 129.57, 130.12, 135.66 (ArACH), 141.39,
144.15 (ArAC), 154.55 (C-5), 174.26 (C-2), 187.34 (CO); ms
m/z: 296 (Mþ, 25), 185 (44), 111 (65), 104 (100), 76 (76), 65
(44). Anal. Calcd. for C15H8N2O3S: C, 60.80; H, 2.72; N,
9.45; S, 10.82. Found: C, 61.02; H, 2.86; N, 9.28; S, 11.03.
2-(5-(Furan-2-yl)-1,3,4-oxadiazol-2-(3H)-ylidene)-1H-indene-
1,3-(2H)-dione (4c). This compound was obtained as reddish
brown crystals (methanol), mp 228–230ꢁC; ir: NH 3345, CO
1720, C¼¼N 1620, Aryl and C¼¼C 1605, CAOAC 1090; 1H
NMR: d 7.14–8.21 (m, 7H, ArAH and furan-H), 12.59 (br,
1H, oxadiazole-NH); 13C NMR: d 91.65 (indene-C-2), 126.03,
126.33, 127.41, 134.88 (ArACH and furan-CH), 140.97,
142.85, 143.66, 145.54 (ArAC and furan-C-2, C-5), 155.12
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A. A. Hassan, Y. R. Ibrahim, and A. M. Shawky
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2215, CO (1715, 1665), C¼¼N 1620, ArAC¼¼C 1590; 1H
NMR: d 7.28–8.49 (m, 8H, ArAH and pyridine-H); 13C NMR:
d 104.92 (C-3a), 118.12 (CN), 121.74 (C-3), 126.32, 126.53,
127.19, 127.44, 130.47, 132.22 (ArACH and pyridine-CH),
134.65 (ArAC), 148.11, 148.72 (pyridine-C-2, C6), 149.79 (C-
8b), 167.70 (CO), 189.29 (C-4); ms: m/z 300 (Mþ, 28), 274
(9), 246 (19), 140 (38), 106 (100), 104 (91), 77 (83), 65 (54).
Anal. Calcd. for C17H8N4O2: C, 68.00; H, 2.69; N, 18.66.
Found: C, 67.78; H, 2.78; N, 18.83.
1-(1H-Indole-2-carbonyl)-4-oxo-1,4-dihydroindeno[1,2-c]
pyrazole-3-carbonitrile (6e). This compound was obtained as
yellow crystals (methanol), mp 311–313ꢁC; ir: NH 3365, CN
2220, CO (1710, 1665), C¼¼N 1625, ArAC¼¼C 1595; 1H
NMR: d 6.64 (s, 1H, indole-H), 7.28–8.19 (m, 8H, ArAH),
11.69 (br, 1H, indole-NH); 13C NMR: d 99.91 (indole-CH),
105.06 (C-3a), 118.19 (CN), 121.69 (C-3), 126.12, 126.22,
126.45, 126.86, 127.61, 128.22, 130.51 (ArACH), 132.69,
134.18, 134.87, 135.29 (ArAC), 149.76 (C-8b), 167.72 (CO),
189.31 (C-4); ms: m/z 338 (Mþ, 27), 312 (21), 284 (46), 144
(87), 140 (51), 104 (79), 91 (100), 77 (82), 65 (43); Anal.
Calcd. for C20H10N4O2: C, 71.00; H, 2.98; N, 16.56. Found:
C, 70.83; H, 3.11; N, 16.77.
Reaction of carbohydrazides 1a–e with 3. Carbohydra-
zides 1a–e (1.0 mmol) were dissolved in 20 mL absolute etha-
nol with two drops of pipridine and added to the indolone 3
(1 mmol) in 25 mL absolute ethanol, the mixture was heated
under reflux for 5 h (for runs 1a–c with 3), and 7 h (for runs
1d,e with 3), cooled to room temperature. Concentrated and
subjected to PLC using toluene/ethyl acetate (4:1) to give
numerous colored zones, the two intense of which were
removed and extracted. The fastest migrating one contained
substituted spiro(indoline-3,20-[1,3,4]oxadiazol)-2-one 11a–e,
the second zone contained substituted carbonylpyrazolo[3,4-
b]indole-3-carbonitrile 13a–e. Extraction of the zones with ac-
etone and crystallized.
50-(Pyridin-2-yl)-30H-spiro(indene-2,20-[1,3,4]oxadiazole)-
1,3-dione (5d). This compound was obtained as orange crys-
tals (acetonitrile), mp 214–216ꢁC, ir: NH 3330, CO 1715,
C¼¼N 1630, CAOAC 1095; 1H NMR: d 7.28–8.46 (m, 8H,
ArAH and pyridine-H), 12.50 (br, 1H, oxadiazole-NH); 13C
NMR: d 103.55 (C-2,20), 126.11, 126.47, 126.96, 130.54,
132.16 (ArACH and pyridine-CH), 134.71 (ArAC), 147.93,
148.67 (pyridine-C2, C6), 156.79 (C-50), 187.56 (C-1,3); ms
m/z: 279 (Mþ, 51), 251 (26), 145 (55), 106 (67), 104 (89), 78
(100), 77 (92), 65 (41); Anal. Calcd. for C15H9N3O3: C, 64.52;
H, 3.25; N, 15.05. Found: C, 64.71; H, 3.36; N, 14.87.
50-(1H-Indol-2-yl)-30H-spiro(indene-2,20-[1,3,4]oxadi-azole)-
1,3-dione (5e). This compound was obtained as orange crystals
(methanol), mp 283–285ꢁC; ir: 3380-NH 3325, CO 1710,
C¼¼N 1630, CAOAC 1095; 1H NMR: d 6.61 (s, 1H, indole-
H), 7.19–8.22 (m, 8H, ArAH), 11.71 (br, 1H, indole-NH),
12.53 (br, 1H, oxadiazole-NH); 13C NMR: d 99.76 (indole-
CH), 103.42 (C-2,20), 122.87 (indole-CH-2), 125.88, 126.29,
126.44, 127.63, 128.41, 130.55 (ArACH), 132.77, 133.52,
134.89 (ArAC), 156.36 (C-50), 187.64 (C-1,3); ms m/z: 317
(Mþ, 18), 289 (26), 144 (57), 145 (37), 116 (29), 104 (76), 91
(89), 77 (100), 65 (71); Anal. Calcd. for C18H11N3O3: C,
68.14; H, 3.49; N, 13.24. Found: C, 67.88; H, 3.36; N, 13.45.
1-Benzoyl-4-oxo-1,4-dihydroindeno[1,2-c]pyrazole-3-car-
bonitrile (6a). This compound was obtained as pale yellow
crystals (acetonitrile), mp 273–275ꢁC; ir: ArACH 3090, CN
2215, CO (1720, 1660), C¼¼N 1620, ArAC¼¼C 1590; 1H
NMR: d 7.31–8.21 (m, 9H, ArAH); 13C NMR: d 105.12 (C-
3a), 118.12 (CN), 121.75 (C-3), 126.76, 126.94, 127.85,
129.22, 130.12, 130.41 (ArACH), 132.18, 134.71 (ArAC),
149.53 (C-8b), 167.54 (CO), 189.27 (C-4); ms m/z: 299 (Mþ,
26), 273 (16), 245 (41), 140 (61), 105 (100), 104 (74), 77
(56), 65 (64); Anal. Calcd. for C18H9N3O2: C, 72.24; H, 3.03;
N, 14.04. Found: C, 72.39; H, 2.89; N, 13.83.
4-Oxo-1-(thiophene-2-carbonyl)-1,4-dihydroindeno[1,2-c]
pyrazole-3-carbonitrile (6b). This compound was obtained as
pale yellow crystals (ethanol), mp 296–298ꢁC; ir: ArACH
3105, CN 2220, CO (1715, 1665), C¼¼N 1620, ArAC¼¼C
50-Phenyl-30H-spiro(indoline-3,20-[1,2,4]oxadiazol)-2-one
(11a). This compound was obtained as yellow crystals (etha-
nol), mp 231–233ꢁC; ir: NH’s 3310–3380, CO 1710, C¼¼N
1620, Ar and C¼¼C 1600, CAOAC 1085; 1H NMR: d 7.22–
7.82 (m, 9H, ArAH), 9.89 (br, 1H, indolone-NH), 12.56 (br,
1
1590; H NMR: d 7.22–8.16 (m, 7H, ArAH and thiophene-H);
13C NMR: d 104.96 (C-3a), 118.19 (CN), 121.71 (C-3),
126.75, 128.45, 129.97, 130.26, 130.54 (ArACH and thio-
phene-CH), 132.28 (ArAC), 139.26 (thiophene-C), 149.67 (C-
8b), 167.49 (CO), 189.34 (C-4); ms m/z: 305 (Mþ, 22), 279
(19), 251 (46), 140 (41), 111 (100), 104 (83), 77 (69), 65 (59);
Anal. Calcd. for C16H7N3O2S: C, 62.94; H, 2.31; N, 13.76; S,
10.50. Found: C, 63.19; H, 2.43; N, 13.54; S, 10.68.
13
1H, oxadiazole-NH); C NMR: d 93.74 (C-3 ¼ C-20), 126.54,
127.17, 127.94, 128.76, 131.24, 132.16 (ArACH), 135.33,
138.19, 142.55 (ArAC), 154.85 (C-50), 177.98 (CO); ms: m/z
265 (Mþ, 36), 237 (17), 132 (56), 119 (68), 105 (74), 91 (82),
77 (100), 65 (42); Anal. Calcd. for C15H11N3O2: C, 67.92; H,
4.18; N, 15.84. Found: C, 68.16; H, 4.02; N, 16.05.
50-(Thiophen-2-yl)-30H-spiro(indoline-3,20-[1,2,4]oxadi-azol)-
2-one (11b). This compound was obtained as yellow crystals
(acetonitril), mp 259–261ꢁC; ir: NH’s 3330–3375, CO 1720,
C¼¼N 1625, Ar and C¼¼C 1590, CAOAC 1080; 1H NMR: d
7.11–7.74 (m, 7H, ArAH and thiophene-H), 9.93 (br, 1H,
indolone-NH), 12.46 (br, 1H, oxadiazole-NH); 13C NMR: d
93.65 (C-3 ¼ C-20), 126.17, 127.37, 127.88, 129.17, 130.17,
131.44 (ArACH and thiophene-CH), 132.16, 137.95, 142.35
(ArAC and thiophene-C), 155.12 (C-50), 178.09 (CO); ms: m/z
271 (Mþ, 37), 139 (42), 119 (25), 111 (100), 91 (63), 77 (87),
65 (56); Anal. Calcd. for C13H9N3O2S: C, 57.55; H, 3.34; N,
15.49; S, 11.82. Found: C, 57.77; H, 3.21; N, 15.26; S, 12.06.
50-(Furan-2-yl)-30H-spiro(indoline-3,20-[1,2,4]oxadiazol)-2-
one (11c). This compound was obtained as pale yellow crys-
tals (ethanol), mp 218–219ꢁC; ir: NH’s 3315–3380, CO 1715,
1-(Furan-2-carbonyl)-4-oxo-1,4-dihydroindeno[1,2-c]-
pyrazole-3-carbonitrile (6c). This compound was obtained as
pale yellow crystals (ethanol), mp 265–267ꢁC; ir: ArACH
3085, CN 2210, CO (1715, 1660), C¼¼N 1615, ArAC¼¼C
1585, CAOAC 1085; 1H NMR: d 7.31–8.15 (m, 7H, ArAH
and furan-H); 13C NMR: d 105.09 (C-3a), 118.22 (CN),
121.68 (C-3), 125.94, 126.35, 128.90, 130.56 (ArAC and
furan-C), 141.18, 142.26 (furan-C-2, C-5), 149.74 (C-8b),
167.61 (CO), 189.28 (C-4); ms: m/z 289 (Mþ, 39), 253 (22),
225 (32), 130 (29), 104 (74), 95 (81), 77 (100), 65 (61);
C16H7N3O3: C, 66.44; H, 2.44; N, 14.53. Found: C, 66.27; H,
2.57; N, 14.71.
4-Oxo-1-picolinoyl-1,4-dihydroindeno[1,2-c]pyrazole-3-
carbonitrile (6d). This compound was obtained as yellow
crystals (acetonitrile), mp 284–286ꢁC; ir: ArACH 3115, CN
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2009
Dicyanomethylene Compounds and Heterocyclization of Substituted Carbohydrazides
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1
C¼¼N 1620, Ar and C¼¼C 1595, CAOAC 1085; 1H NMR: d
7.08–7.69 (m, 7H, ArAH and furan-H), 9.90 (br, 1H, indo-
lone-NH), 12.48 (br, 1H, oxadiazole-NH); 13C NMR: d 93.68
(C-3 ¼ C-20), 125.87, 126.82, 128.76, 129.97, 130.18 (ArACH
and furan-CH), 132.76, 141.55, 141.96, 144.12 (ArAC and
furan-C-2, C-5), 155.29 (C-50), 177.84 (CO); ms m/z 255 (Mþ,
27), 227 (23), 142 (19), 119 (26), 85 (69), 91 (82), 77 (100),
65 (44); Anal. Calcd. for C13H9N3O3: C, 61.18; H, 3.55; N,
16.46. Found: C, 60.94; H, 3.64; N, 16.65.
CO 1665, C¼¼N 1625, Ar and C¼¼C 1585, CAOAC 1090; H
NMR: d 7.31–7.96 (m, 7H, ArAH and furan-H), 11.95 (br,
1H, pyrazole-NH); 13C NMR: d 101.93 (C-3a), 117.97 (CN),
126.44, 128.57, 129.64, 130.26, 130.86, 132.42 (ArACH,
furan-CH and C-3), 135.57, 141.84, 145.33, 147.87 (ArAC
and furan-C-2, C-5), 150.14 (C-8a), 169.36 (CO); ms: m/z 276
(Mþ, 39), 181 (23), 154 (33), 126 (18), 95 (84), 91 (100), 77
(67), 65 (52); Anal. Calcd. for C15H8N4O2: C, 65.22; H, 2.92;
N, 20.28. Found: C, 65.41; H, 3.05; N, 20.07.
50-(Pyridin-2-yl)-30H-spiro(indoline-3,20-[1,2,4]oxadiazol)-
2-one (11d). This compound was obtained as yellow crystals
(acetonitril), mp 236–235ꢁC; ir: NH’s 3325–3380, CO 1725,
C¼¼N 1630, Ar and C¼¼C 1600, CAOAC 1080; 1H NMR: d
7.24–8.46 (m, 8H, ArAH and pyridine-H), 9.86 (br, 1H, indo-
lone-NH), 12.49 (br, 1H, oxadiazole-NH); 13C NMR: d 93.75
(C-3 ¼ C-20), 126.26, 126.53, 127.79, 128.88, 130.16, 130.35
(ArACH and pyridine-CH), 132.19, 141.76 (ArAC), 147.23,
148.89 (pyridine-C-2, C-6), 155.28 (C-50), 178.05 (CO); ms:
m/z 266 (Mþ, 22), 160 (36), 132 (28), 119 (41), 106 (100), 91
(57), 77 (83), 65 (61); Anal. Calcd. for C14H10N4O2: C, 63.15;
H, 3.79; N, 21.04. Found: C, 62.92; H, 3.91; N, 20.88.
1-Picolinyl-1,2-dihydropyrazolo[3,4-b]indole-3-carbonitrile
(13d). This compound was obtained as yellow crystals (aceto-
nitrile), mp 290–292ꢁC; ir: NH 3405, CN 2220, CO 1655,
C¼¼N 1630, Ar and C¼¼C 1610; 1H NMR: d 7.33–8.41 (m,
8H, ArAH and pyridine-H), 11.93 (br, 1H, pyrazole-NH); 13C
NMR: d 102.12 (C-3a), 118.27 (CN), 126.45, 127.44, 128.55,
129.79, 130.16, 131.26, 132.19 (ArACH, pyridine-CH and C-
3), 135.76, 141.88 (ArAC), 148.92, 150.12, 151.64 (pyridine-
C-2, C-6 and C-8a), 169.77 (CO); ms: m/z 287 (Mþ, 43), 181
(18), 154 (25), 126 (13), 106 (75), 91 (100), 77 (83), 65 (66);
Anal. Calcd. for C16H9N5O: C, 66.89; H, 3.16; N, 24.38.
Found: C, 67.04; H, 3.02; N, 24.21.
1-(1H-Indole-2-carbonyl-1,2-dihydropyrazolo[3,4-b]indole-
3-carbonitrile (13e). This compound was obtained as yellow
crystals (methanol), mp 304–306ꢁC; ir: NH’s 3290–3415, CN
50-(1H-Indol-2-yl)-30H-spiro(indoline-3,20-[1,2,4]oxadi-azol)-
2-one (11e). This compound was obtained as orange crystals
(methanol), mp 187–188ꢁC; ir: NH’s 3290–3370, CO 1720,
C¼¼N 1630, Ar and C¼¼C 1605, CAOAC 1090; 1H NMR: d
6.57 (indole-CH), 7.02–7.74 (m, 8H, ArAH), 9.81 (br, 1H,
indolone-NH), 11.75 (br, 1H, indole-NH), 12.55 (br, 1H, oxa-
1
2215, CO 1660, Ar and C¼¼C 1595; H NMR: d 6.62 (s, 1H,
indole-H), 7.18–7.88 (m, 8H, ArAH), 11.71 (br, 1H, indole-
NH), 11.97 (br, 1H, pyrazole-NH); 13C NMR: d 101.94 (C-
3a), 118.29 (CN), 123.87 (indole-CH), 126.37, 126.94, 128.54,
129.17, 130.29, 131.47, 132.31 (ArACH and C-3), 135.29,
138.77, 139.27, 140.81, 142.16 (ArAC and indole-C-2),
149.93 (C-8a), 169.65 (CO); ms: m/z 325 (Mþ, 46), 181 (27),
154 (28), 144 (86), 91 (92), 77 (100), 65 (55); Anal. Calcd.
for C19H11N5O: C, 70.15; H, 3.41; N, 21.53. Found: C, 69.93;
H, 3.55; N, 21.31.
13
diazole-NH); C NMR: d 93.66 (C-3 ¼ C-20), 101.96 (indole-
CH), 126.26, 127.53, 128.82, 129.96, 130.31, 130.45
(ArACH), 132.26, 135.26, 138.92, 141.22, 142.11 (ArAC and
indole-C-2), 154.89 (C-50), 177.90 (CO); ms: m/z 304 (Mþ,
33), 276 (31), 144 (28), 132 (26), 119 (54), 91 (100), 77 (67),
65 (41); Anal. Calcd. for C17H12N4O2: C, 67.10; H, 3.97; N,
18.41. Found: C, 66.87; H, 4.12; N, 18.18.
1-Benzoyl-1,2-dihydropyrazolo[3,4-b]indole-3-carbonitrile
(13a). This compound was obtained as pale yellow crystals
(methanol), mp 279–281ꢁC; ir: NH 3410, CN 2210, CO 1665,
C¼¼N 1625, Ar and C¼¼C 1590; 1H NMR: d 7.34–7.96 (m,
9H, ArAH), 11.96 (br, 1H, pyrazole-NH); 13C NMR: d 101.86
(C-3a), 118.16 (CN), 126.37, 126.89, 128.85, 129.71, 130.16,
130.97, 132.12 (ArACH and C-3), 136.33, 138.91, 141.74,
142.23 (ArAC), 150.33 (C-8a), 169.44 (CO); ms: m/z 286
(Mþ, 54), 181 (37), 154 (42), 126 (18), 105 (62), 91 (75), 77
(100), 65 (64); Anal. Calcd. for C17H10N4O: C, 71.32; H,
3.52; N, 19.57. Found: C, 71.55; H, 3.39; N, 19.35.
REFERENCES AND NOTES
[1] Junek, H.; Aigner, H.; Fischer-Colbrie, H. Monatsh Chem
1972, 103, 639.
[2] Rappopart, Z.; Ladkani, D. J Chem Soc [Perkin 2] 1973,
1045.
¨
[3] Boila-Gockel, A.; Fabian, W. M. F.; Junek, H. Liebigs Ann
Chem 1996, 397.
[4] Aigner, H.; Junek, H.; Sterk, H. Monatsh Chem 1970, 101,
1145.
[5] Fischer-Colbrie, H.; Aigner, H.; Junek, H. Monatsh Chem
1975, 106, 743.
1-(Thiophene-2-carbonyl)-1,2-dihydropyrazolo[3,4-b]-indole-
3-carbonitrile (13b). This compound was obtained as pale yel-
low crystals (acetonitrile), mp 295–297ꢁC; ir: NH 3395, CN
[6] Junek, H.; Hermetter, A.; Fischer-Colbrie, H.; Aigner, H.
Tetrahedron Lett 1973, 2995.
1
2215, CO 1660, C¼¼N 1630, Ar and C¼¼C 1600; H NMR: d
[7] Junek, H.; Fischer-Colbrie, H.; Hermetter, A. Z Naturforsch
1977, 32b, 2995.
7.23–7.90 (m, 7H, ArAH and thiophene-H), 11.98 (br, 1H,
pyrazole-NH); 13C NMR: d 102.05 (C-3a), 118.24 (CN),
126.56, 126.84, 128.33, 129.61, 130.23, 130.85, 132.26
(ArACH, thiophene-CH and C-3), 135.89, 142.33, 146.13
(ArAC and thiophene-C-2), 149.98 (C-8a), 169.64 (CO); ms:
m/z 292 (Mþ, 28), 181 (12), 153 (31), 126 (24), 111 (100), 91
(47), 77 (63), 65 (55); Anal. Calcd. for C15H8N4OS: C, 61.63;
H, 2.76; N, 19.17; S, 11.16. Found: C, 61.84; H, 2.63; N,
18.91; S, 10.97.
[8] Nesterov, V. N.; Aitov, I. A.; Sharanin, A. Y.; Struchkov,
T. Y. Russ Chem Bull 1996, 45, 164.
[9] (a) Bespalov, B. P.; Getmanova, E. V.; Abolin, A. G. J Org
Chem (USSR) 1981, 17, 1612; (b) Bespalov, B. P.; Getmanova, E. V.;
Abolin, A. G. Zh Org Khim 1980, 16A, 1896.
[10] Junek, H.; Klad, M.; Biza, P.; Geringer, M.; Sterk, H. Lie-
bigs Ann Chem 1990, 741.
¨
¨
[11] Dopp, D.; Juschke, S.; Henkel, G. Z Naturforsch 2002, 576,
1-(Furan-2-carbonyl)-1,2-dihydropyrazolo[3,4-b]indole-3-
carbonitrile (13c). This compound was obtained as pale yel-
low crystals (ethanol), mp 261–263ꢁC; ir: NH 3390, CN 2220,
460.
[12] Hassan, A. A.; Ibrahim, Y. R.; Mohamed, N. K.; Mourad,
A. E. Liebigs Ann Chem 1991, 71.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

622
A. A. Hassan, Y. R. Ibrahim, and A. M. Shawky
Vol 46
[13] Hassan, A. A.; Mohamed, N. K.; Ibrahim, Y. R.; Mourad,
[24] Hassan, A. A.; Mourad, A. E.; Abou-Zied, A. H. J Hetero-
cycl Chem 2008, 45, 323.
A. E. Liebigs Ann Chem 1993, 659.
[14] Hassan, A. A.; Mohamed, N. K.; El-Tamany, E. H.; Ali,
B. A.; Mourad, A. E. Monatsh Chem 1995, 126, 659.
[15] Hassan, A. A.; Mohamed, N. K.; Ali, A. A.; Mourad, A. E.
Monatsh Chem 1997, 128, 61.
[25] Charistos, D. A.; Vagenas, G. V.; Tzavellas, L. C.; Tsoleri-
dis, C. A.; Rodios, N. A. J Heterocycl Chem 1994, 31, 1593.
[26] Kaupp, G.; Schmeyers, J.; Boy, J. J Prakt Chem 2000, 342, 269.
[27] Ali, R.; Mishra, B.;Nizamuddin.Indian J Chem 1989, 28B, 526.
[28] Somogyi, L. Bull Chem Soc Jpn 2001, 74, 873.
[29] Monge, A.; Palop, J.; Ramirez, C.; Font, M.; Fernandez-
Alvarez, E. Eur J Med Chem 1991, 26, 79.
¨
[16] Dopp, D.; Hassan, A. A.; Nour El-Din, A. M.; Mourad,
A. E.; Lehmann, C. W.; Rust, J. Tetrahedron 2006, 62, 11618.
[17] Fatiadi, A. J. Synthesis 1978, 165.
[18] Abdel-Latif, F. F.; Ahmed, E. KH.; Mekheimer, R.;
Mashaly, M. M. Arch Pharm Res 1997, 20, 507.
[19] El-Saghier, A. M. M. Phosphours Sulfur Silicon Relat Elem
2004, 179, 1293.
[30] Azizian, J.; Shaabanzadeh, M.; Hatamjafari, F.; Mohamme-
dizadeh, M. R. ARKIVOC 2006, xi, 47.
[31] Curtius, T.; Thyssen, J. J Prakt Chem 1902, 7, 65.
[32] Cook, M. J.; Bes, E. J. Tetrahedron 1968, 24, 4501.
[33] Iqbal, R.; Malik, F. J Chem Soc Pak 1984, 6, 43.
[20] Al-Omran, E.; El-Ghamry, I.; El-Nagdi, M. H. Org Prep
Proced Int 1998, 30, 363.
ˆ
[34] Penez, S.; Lasheras, B.; Oset, C.; Monge, A. J Heterocycl
[21] Dworczak, R. Monatsh Chem 1991, 122, 172.
[22] El-Ahl, A. A.; Afeefy, H.; Metwally, M. A. J Chem Res
1994, 14.
Chem 1997, 34, 1527.
[35] Marco, J. I. J Heterocycl Chem 1998, 35, 475.
[36] Cruces, M. A.; Elorriage, C.; Fernandes-Alvarez, E.
Biochem Pharmacol 1990, 40, 535.
¨
[23] Dopp, D.; Gomaa, M. A.; Henkel, G.; Nour El-Din, A. M.
J Chem Soc [Perkin 2] 1996, 573.
[37] Chatterjee, S. J Chem Soc B 1969, 725.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet