Reactions of 2-(diformylmethylidene)-3,3-dimethylindole with hydrazides: Synthesis of new pyrazolylindolenine derivatives-the unprecedented one-pot pyrazole-thiadiazole double annulation

Article abstract of DOI:10.1002/jhet.575

A series of new pyrazolylindolenine derivatives has been synthesized through the reaction of 2-(diformylmethylidene)-3,3-dimethylindole (diformyl), prepared by the Vilsmeier reaction, with six different hydrazides. Although the reaction of p-toluenesulfon

Full text of DOI:10.1002/jhet.575

May 2011
Reactions of 2-(Diformylmethylidene)-3,3-dimethylindole with
Hydrazides: Synthesis of New Pyrazolylindolenine
Derivatives—The Unprecedented One-Pot
663
Pyrazole–Thiadiazole Double Annulation
Hamid Khaledi,* Hapipah Mohd Ali, Noel Francis Thomas,
and Seik Weng Ng
Department of Chemistry, University of Malaya, Kuala Lumpur 50603, Malaysia
*E-mail: khaledi@siswa.um.edu.my
Received May 1, 2010
DOI 10.1002/jhet.575
Published online 29 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
A series of new pyrazolylindolenine derivatives has been synthesized through the reaction of 2-(difor-
mylmethylidene)-3,3-dimethylindole (diformyl), prepared by the Vilsmeier reaction, with six different
hydrazides. Although the reaction of p-toluenesulfonylhydrazide and S-benzyldithiocarbazide with
diformyl yielded the expected pyrazolylindolenines as the sole products, the initial products of the reac-
tions of diformyl with semicarbazide, thiosemicarbazide, and carbohydrazide underwent cleavage. The
reaction of diformyl with thiocarbohydrazide resulted in a unique one-pot formation of pyrazole and
thiadiazole rings, conjugated with the indolenine component. The solid state structures of these hetero-
cycles were established by X-ray crystallographic analysis.
J. Heterocyclic Chem., 48, 663 (2011).
INTRODUCTION
more, it was reported that heating the hydrazones in
refluxing ethanol gave rise to 4-(3,3-dimethylindol-2-yl)-
substituted pyrazoles 3, with migration of the double
bond into the dihydropyrrole ring (Scheme 1). We have
now been able to determine the structure of the reported
monohydrazone 2. Moreover, we report the result of our
investigation on the reaction of the diformyl 1 with
hydrazides. Crystal structures of the synthesized com-
pounds were also determined using single-crystal X-ray
diffraction data.
Pyrazole derivatives constitute an important class of
therapeutic agents in medicinal chemistry owing to their
effectiveness as antitumor [1], anti-inflammatory [2],
antihypertensive [3], antipsychotic [4], and neuroprotec-
tive [5] agents. Among the several syntheses of pyra-
zoles, which have been developed so far, one of the
most common methods involves the reaction of 1,3-
dicarbonyls with hydrazine derivatives [6]. The reaction
proceeds by the initial formation of the monohydrazones
that are then converted to the pyrazoles by the action of
heat or acids.
RESULTS AND DISCUSSION
Some years ago, Baradarani and coworkers described
the reaction of 2,3,3-trimethylindolenine with the Vils-
meier reagent to produce aminomethylene-malondialde-
hyde 1 (Fig. 1) [7]. Later work by the same group [8]
showed that this 2-(diformylmethylidene)-3,3-dimethy-
lindole (diformyl) compound can react with arylhydra-
zines at room temperature to generate monohydrazones
2a or 2b as pure products, although it was not possible
to ascertain which carbonyl group had reacted. Further-
The 1H NMR spectrum of the monohydrazone
obtained from the reaction of the diformyl and phenyl-
hydrazine shows the gem-dimethyl hydrogens at d 1.72
ppm, the imine hydrogen at d 8.30 ppm, and the alde-
hyde hydrogen at d 10.00 ppm. To elucidate the struc-
ture of the compound, we have examined the possible
NOE correlations between these hydrogens. The com-
pound shows no NOE effect between the gem-methyl
C
V
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664
H. Khaledi, H. M. Ali, N. F. Thomas, and S. W. Ng
Vol 48
Figure 1. 2-(Diformylmethylidene)-3,3-dimethylindole (1).
hydrogens and the imine hydrogen, whereas the effect
was observed between the aldehyde and the methyl
hydrogens. Therefore, the structure of the monohydra-
zone is unambiguously 2b. This was further established
by X-ray crystallographic analysis. Figure 2a shows the
solid state structure of 2b in which the imine link adopts
the trans configuration stabilized by NHꢀꢀꢀN hydrogen
bonding. The greater reactivity of the C(13) in the
diformyl 1 in comparison with C(12) may be because of
the Bu¨rgi–Dunitz direction of approach of the hydrazine,
which would be blocked by the gem-dimethyl group if
nucleophilic attack took place at the C12 [9]. Attack at
the C13, activated by intramolecular H-bonding, takes
place away from the geminal methyl groups.
The hydrazone was then converted to pyrazolylindole-
nine 3 by heating. The X-ray crystal structure of 3 shows
that the indolenine and the pyrazole components are nearly
coplanar, attesting to conjugation between these two het-
erocycles. This system and the third aromatic ring, i.e., the
phenyl group are not coplanar (Fig. 2b). The selected bond
distances and bond angels of 2b and 3 are given in Table 1.
To explore further aspects of the chemistry of this poly-
functional compound, we studied the reactions of the
diformyl 1 with different hydrazides (Scheme 2).
Figure 2. The crystal structure of compounds (a) 2b and (b) 3 .
The reaction of p-toluenesulfonylhydrazide was carried
out in refluxing ethanol in the presence of acetic acid to
give compound 4 as the only product. Under the same con-
ditions S-benzyldithiocarbazide [10] reacted efficiently with
the diformyl 1 to give the pyrazole 5. It is noteworthy that
neither the p-toluenesulfonyl nor the S-benzyldithiocar-
bonyl groups were cleaved under the applied conditions.
Diformyl 1 reacted with semicarbazide hydrochloride
in ethanol at room temperature to form the 1-carbamoyl-
pyrazole 6. However, conducting the reaction in refluxing
ethanol resulted in loss of the carbamoyl group, leading to
the indoleninium chloride salt 7. Similarly, the reaction of
thiosemicarbazide with diformyl 1 afforded the 1-thiocar-
bamoylpyrazole 8 and (after loss of the thiocarbamoyl
group) the indoleninium thiocyanate salt 9, as a mixture.
Our attempts to prevent the loss of the thiocarbamoyl moi-
ety were unsuccessful; however, the pure products were
easily obtained by sequential crystallization. 1-(Thio)carba-
moylpyrazole derivatives are an intriguing class of chelat-
ing ligands and important intermediates in synthesizing a
Scheme 1
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Reactions of 2-(Diformylmethylidene)-3,3-dimethylindole with Hydrazides: Synthesis of New
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Pyrazolylindolenine Derivatives—The Unprecedented One-Pot Pyrazole–Thiadiazole Double Annulation
Table 1
Selected bond lengths and bond angles for compounds 2b and 3.
Compound 2b
Compound 3
˚
Bond lengths (A)
O(1)AC(12)
N(1)AC(10)
N(1)AC(1)
N(2)AC(13)
N(2)AN(3)
N(3)AC(14)
C(10)AC(11)
C(11)AC(12)
C(11)AC(13)
1.2344(19)
1.344(2)
1.402(2)
1.288(2)
1.3652(19)
1.387(2)
1.391(2)
1.430(2)
1.452(2)
N(1)AC(10)
N(1)AC(1)
N(2)AC(13)
N(2)AN(3)
N(3)AC(12)
N(3)AC(14)
C(10)AC(11)
C(11)AC(12)
C(11)AC(13)
1.2995(16)
1.4189(17)
1.3158(18)
1.3606(15)
1.3437(16)
1.4261(17)
1.4503(19)
1.3751(18)
1.4010(19)
Bond angles (ꢁ)
C(13)AN(2)AN(3)
N(2)AN(3)AC(14)
C(9)AC(7)AC(8)
N(1)AC(10)AC(11)
C(12)AC(11)AC(13)
O(1)AC(12)AC(11)
N(2)AC(13)AC(11)
117.29(13)
119.07(13)
110.85(13)
120.94(14)
116.51(14)
125.64(16)
122.85(14)
N(2)AN(3)AC(14)
C(9)AC(7)AC(8)
N(1)AC(10)AC(11)
119.49(11)
111.58(12)
120.38(12)
Scheme 2
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H. Khaledi, H. M. Ali, N. F. Thomas, and S. W. Ng
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Table 2
Selected bond lengths and bond angles for compound 9.
˚
Bond lengths (A)
S(1)AC(14)
N(1)AC(10)
N(2)AC(13)
N(2)AN(3)
N(3)AC(12)
1.648(2)
1.300(2)
1.324(2)
1.370(2)
1.321(2)
1.162(2)
1.427(3)
1.398(3)
1.420(3)
N(4)AC(14)
C(10)AC(11)
C(11)AC(12)
C(11)AC(13)
Bond angles (ꢁ)
C(9)AC(7)AC(8)
N(1)AC(10)AC(11)
N(4)AC(14)AS(1)
110.26(15)
122.14(17)
178.79(17)
and 9 confirm the formation of indoleninium salts (Fig.
3). The selected interatomic distances and bond angels for
compound 9 are listed in Table 2.
Finally, the reactions of the dialdehyde with carbohy-
drazide and thiocarbohydrazide were investigated.
Regardless of the experimental conditions, the only prod-
uct obtained from the reaction with carbohydrazide was
(1H-pyrazole-4-yl)-3H-indole 10, which was also
obtained from the reaction of hydrazine and the diformyl
[8]. It would appear that the first formed intermediate is
very unstable and immediately decomposes to compound
10. The reaction of the dialdehyde with thiocarbohydra-
zide led to the formation of the pyrazole-N-thiocarbohy-
drazide 11 and the thiadiazole-2-thione 12. To the best of
our knowledge, this protocol for formation of thiadiazole
ring is unprecedented as is the arrangement of heterocy-
clic systems, i.e., pyrazole-N-yl-1,3,4-thiadiazole-2-thi-
one. Although thiadiazole-2-thione fused to the C atom of
pyrazoles is known [13], analogous fusion to the N atom
of pyrazoles is not. The crystal structure of compounds 11
and 12 are depicted in Figure 4 and selected bond lengths
and bond angles are given in Table 3. The structure of 12
shows the three heterocyclic rings as coplanar, indicating
conjugation between them, in contrast to compound 3.
This presumption is supported by the shorter bond length
˚
of N(3)AC(14) in 12 (1.39 A) compared with the one in 3
˚
(1.43 A), attesting its significant double bond character.
The reaction mechanism for the formation of pyrazoly-
lindolenine 11 is fundamentally the same as that for the
formation of the other pyrazolylindolenines. To account
for the formation of compound 12 two possible mecha-
nisms were considered (Scheme 3). One involves intermo-
lecular reaction of two molecules of compound 11 (i) [14].
The second alternative requires the nucleophilic attack of a
second molecule of thiocarbohydrazide on compound 11
(ii). The intermediate then undergoes cyclocondensation to
form the five membered ring of 1,3,4-thiadiazole. The first
mechanism may be ruled out, as it would lead to formation
of pyrazolylindolenine 10 that was not detected under the
Figure 3. The crystal structure of compounds (a) 7 and (b) 9.
variety of heterocyclic compounds [11]. It is well known
that the (thio)carbamoyl group tends to cleave on heating
or by the action of bases. In fact, this cleavage can lead to
an interesting series of metal complexes in coordination
chemistry [12]. Evidently, the indolenine nitrogen of com-
pounds 6 and 8 acts as a base and is then converted to the
related indoleninium salts, facilitating the cleavage of the
(thio)carbamoyl group. The X-ray crystal structures of 7
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Reactions of 2-(Diformylmethylidene)-3,3-dimethylindole with Hydrazides: Synthesis of New
667
Pyrazolylindolenine Derivatives—The Unprecedented One-Pot Pyrazole–Thiadiazole Double Annulation
It is significant that although the synthesis of pyrazoles
using benzoic hydrazide and analogues has been reported
[11e,15], our attempts to react benzoic hydrazide with the
dialdehyde 1 under different conditions were unsuccessful.
In fact, the only product obtained was 1,2-dibenzoylhydra-
zine [16], the product of transacylation of benzoic hydrazide.
EXPERIMENTAL
Melting points were determined using a MEL-TEMP II melting
point instrument and were not corrected. Microanalyses were car-
ried out on a PerkinElmer 2400 elemental analyzer. 1H NMR and
13C NMR spectra were determined with a JEOL Lambda 400
MHz FT NMR (1H: 400 MHz and 13C: 100.4 MHz) spectrometer.
Chemical shifts are given in d values (ppm) using TMS as the in-
ternal standard. The IR spectra were taken with a PerkinElmer
RX1 FTIR spectrophotometer. The mass spectra were taken on an
Agilent 1200 LC/MS. X-ray diffraction data were collected on a
Bruker APEX II CCD diffractometer using Mo Ka radiation. The
structures were solved by direct methods and refined by a full-ma-
trix least-squares procedure based on F2.
Reaction with p-toluenesulfonylhydrazide. A solution of
the dialdehyde (1; 0.43 g, 2 mmol) and p-toluenesulfonylhy-
drazide (0.372 g, 2 mmol) in ethanol (20 mL) in the presence
of acetic acid (0.2 mL) was refluxed for 4 h. The solution was
evaporated to half of its volume and then set aside at room
temperature overnight, whereupon pale yellow crystals of the
compound 4 were obtained.
Figure 4. The crystal structure of compounds (a) 11 and (b) 12.
3,3-Dimethyl-2-[1-(p-toluenesulfonyl)-1H-pyrazol-4-yl]-3H-
indole (4). Yield: 0.65 g, 89%. mp 160–162ꢁC; IR (KBr,
cmꢂ1): 2961, 1594, 1575, 1454, 1377, 1324, 1180, 1094,1075,
673, 585; 1H NMR (DMSO-d6): d 1.43 (s, 6H, gem-CH3),
2.39 (s, 3H, Ar-CH3), 7.25 (m, 1H, Ar-H), 7.32 (m, 1H, Ar-
reaction conditions. Moreover, refluxing an ethanolic solu-
tion of pyrazole-N-thiocarbohydrazide 11 in the presence
of acetic acid did not give compound 12. In the light of the
above, path (ii) is the preferred mechanism of the reaction.
Table 3
Selected bond lengths and bond angles for compounds 11 and 12.
Compound 11
Compound 12
˚
Bond lengths (A)
S(1)AC(14)
N(1)AC(10)
N(1)AC(1)
1.6522(17)
1.297(2)
1.424(2)
1.316(2)
1.3729(19)
1.351(2)
1.410(2)
1.313(2)
1.414(2)
1.450(2)
1.366(2)
1.425(2)
S(1)AC(14)
S(1)AC(15)
S(2)AC(15)
N(5)AC(15)
N(5)AN(4)
N(3)AC(12)
N(3)AN(2)
N(3)AC(14)
N(2)AC(13)
N(1)AC(10)
C(12)AC(11)
C(11)AC(13)
C(11)AC(10)
1.722(3)
1.751(3)
1.657(3)
1.338(3)
1.376(3)
1.353(3)
1.370(3)
1.387(3)
1.320(3)
1.300(3)
1.373(4)
1.419(4)
1.456(3)
N(2)AC(13)
N(2)AN(3)
N(3)AC(12)
N(3)AC(14)
N(4)AC(14)
N(4)AN(5)
C(10)AC(11)
C(11)AC(12)
C(11)AC(13)
Bond angles (ꢁ)
N(2)AN(3)AC(14)
C(14)AN(4)AN(5)
C(8)AC(7)AC(9)
N(1)AC(10)AC(11)
C(13)AC(11)AC(10)
N(4)AC(14)AS(1)
122.07(13)
122.15(16)
110.99(16)
121.97(15)
128.72(16)
125.03(14)
N(2)AN(3)AC(14)
S(2)AC(15)AS(1)
N(1)AC(10)AC(11)
C(8)AC(7)AC(8)#1
119.1(2)
124.15(16)
122.0(2)
111.0(2)
Symmetry transformations used to generate equivalent atoms: #1 x,-yþ1/2,z.
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H. Khaledi, H. M. Ali, N. F. Thomas, and S. W. Ng
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Scheme 3
H), 7.50–7.55 (m, 4H, Ar-H), 8.00 (d, 2H, J ¼ 8.4 Hz, Ar-H),
8.49 (s, 1H, pyrazolyl-H), 9.11 (s, 1H, pyrazolyl-H); 13C NMR
(DMSO-d6): d 21.16, 23.39, 52.90, 118.38, 120.08, 121.48,
125.73, 127.67, 128.05, 130.50, 131.06, 132.86, 144.75,
146.68, 146.78, 152.98, 176.68; MS: m/z 366 (MHþ); Anal.
Calcd for C20H19N3O2S: C, 65.73; H, 5.24; N, 11.50; O, 8.76;
S, 8.77%. Found: C, 65.60; H, 5.24; N, 11.29; S, 8.69%.
Reaction with S-benzyldithiocarbazate. A solution of the
dialdehyde (1; 0.43 g, 2 mmol) and S-benzyldithiocarbazate
[10] (0.396 g, 2 mmol) in ethanol (30 mL) in the presence of
acetic acid (1 mL) was refluxed for 3 h and then cooled at
room temperature. Compound 5 was separated as a yellow
solid on addition of water (30 mL) to the solution. It was col-
lected and washed with cold ethanol and dried over silica gel.
The crystal for X-ray analysis was obtained by slow evapora-
tion of an ethanolic solution at room temperature.
4-(3,3-Dimethyl-3H-indol-2-yl)-pyrazole-1-carbodithioic acid
benzyl ester (5). Yield: 0.52 g, 68%. mp 143–144ꢁC; IR (KBr,
cmꢂ1): 3141, 2968, 1578, 1373, 1169, 1073, 843, 755; 1H
NMR (DMSO-d6): d 1.45 (s, 6H, CH3), 4.61 (s, 2H, CH2),
7.25–7.37 (m, 5H, Ar-H), 7.46 (d, 2H, J ¼ 7.2 Hz, Ar-H), 7.52
(d, 1H, J ¼ 7.2 Hz, Ar-H ), 7.58 (d, 1H, J ¼ 7.6 Hz, Ar-H),
8.66 (s, 1H, pyrazolyl-H), 9.17 (s, 1H, pyrazolyl-H); 13C NMR
(DMSO-d6): d 23.52, 40.32, 52.90, 119.86, 120.27, 121.56,
125.97, 127.74, 127.79, 128.59, 128.62, 129.39, 134.66, 144.95,
146.82, 153.07, 176.56, 199.13; MS: m/z 378 (MHþ); Anal.
Calcd for C21H19N3S2: C, 66.81; H, 5.07; N, 11.13; S, 16.99%.
Found: C, 66.07; H, 5.21; N, 10.96; S, 16.77%.
Reaction with semicarbazide hydrochloride. A solution of
the dialdehyde (1; 0.43 g, 2 mmol) and semicarbazide hydro-
chloride (0.223 g, 2 mmol) was stirred in ethanol (15 mL) at
room temperature for 1 day during which compound 6 precipi-
tated as a pale yellow solid. The solid was filtered, washed
with NaHCO3 aqueous solution and cold ethanol and dried
over silica gel. More solid was obtained from the filtrate. Suit-
able crystal for X-ray analysis was grown in EtOAc. Com-
pound 7 was obtained as colorless crystals by conducting the
reaction in refluxing ethanol for 5 h and leaving the solution at
room temperature for 2 days.
4-(3,3-Dimethyl-3H-indol-2-yl)-pyrazole-1-carboxamide
(6). Yield: 0.36 g, 71%. mp 176–178ꢁC; IR (KBr, cmꢂ1):
1
3383, 3237, 2973, 1741, 1570, 1441, 1356, 1207, 965, 753; H
NMR (DMSO-d6): d 1.57 (s, 6H, CH3), 7.37 (m, 1H, indole-
nine-H), 7.43 (m, 1H, indolenine-H), 7.62–7.65 (m, 2H, indo-
lenine-H), 8.18 (s, 1H, NH2), 8.23 (s, 1H, NH2), 8.68 (s, 1H,
pyrazolyl-H), 9.23 (s, 1H, pyrazolyl-H); 13C NMR (DMSO-
d6): 24.03, 52.98, 114.08, 117.53, 122.48, 127.23, 128.44,
132.22, 142.75, 144.65, 145.29, 149.16, 178.47; MS: m/z 255
(MHþ); Anal. Calcd for C14H14N4O: C, 66.13; H, 5.55; N,
22.03; O, 6.29%. Found: C, 66.02; H, 5.69; N, 21.94%.
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Pyrazolylindolenine Derivatives—The Unprecedented One-Pot Pyrazole–Thiadiazole Double Annulation
3,3-Dimethyl-2-(1H-pyrazol-4-yl)-3H-indolium chloride
(7). Yield: 0.37 g, 75%. mp 266–268ꢁC; IR (KBr, cmꢂ1):
3084, 1611, 1593, 1244, 1154, 762; 1H NMR (DMSO-d6): d
1.68 (s, 6H, CH3), 7.44–7.53 (m, 2H, indolenine-H), 7.66 (d,
1H, J ¼ 7.6 Hz, indolenine-H), 7.76 (d, 1H, J ¼ 7.2 Hz, indole-
nine-H), 9.06 (s, 2H, pyrazolyl-H); 13C NMR (DMSO-d6): d
23.94, 52.57, 109.38, 115.56, 122.93, 127.46, 128.73, 138.52,
141.01, 142.86, 179.64; Anal. Calcd for C13H14ClN3: C, 63.03;
H, 5.70; N, 16.96%. Found: C, 62.90; H, 5.89; N, 16.81%.
Reaction with thiosemicarbazide. A solution of the dialde-
hyde (1; 0.43 g, 2 mmol) and thiosemicarbazide (0.182 g, 2
mmol) in ethanol (20 mL) in the presence of acetic acid (0.5
mL) refluxed for 1 h. The solvent was evaporated, and the
resulting solid was dissolved in EtOAc:Hexane (7:3) and set
aside at room temperature. In a few hours, the yellow crystals
of the compound 9 were obtained. The crystals were collected,
and the solution was set aside for 1 day, whereupon the yellow
crystals of compound 8 were separated out.
5-[4-(3,3-Dimethyl-3H-indol-2-yl)-pyrazol-1-yl]-3H-[1,3,4]thia-
diazole-2-thione (12). Yield: 0.09 g, 14%. mp 312–314ꢁC; IR
(KBr, cmꢂ1): 3076, 2965, 1583, 1431, 1257, 1192, 1059, 739;
1H NMR (DMSO-d6): d 1.48 (s, 6H, CH3), 7.27 (m, 1H, indo-
lenine-H), 7.35 (m, 1H, indolenine-H), 7.53 (d, 1H, J ¼ 6.8
Hz, indolenine-H), 7.58 (d, 1H, J ¼ 7.2 Hz, indolenine-H),
8.58 (s, 1H, pyrazolyl-H), 9.14 (s, 1H, pyrazolyl-H), 10.58 (s,
1H, NH); 13C NMR (DMSO-d6): d 23.43, 52.91, 119.14,
120.07, 121.52, 125.73, 127.48, 127.72, 143.59, 146.82,
152.95, 153.08, 176.86, 186.17; Anal. Calcd for C15H13N5S2:
C, 55.02; H, 4.00; N, 21.39; S, 19.59%. Found: C, 54.77; H,
3.84; N, 21.75; S, 19.36%.
SUPPLEMENTARY DATA
Crystallography data (excluding structure factors) for
the structures in this article have been deposited with
the Cambridge Crystallographic Data Centre as supple-
mentary publication nos. CCDC. 764076–764085.
4-(3,3-Dimethyl-3H-indol-2-yl)-pyrazole-1-carbothioamide
(8). Yield: 0.34 g, 63%. mp 152–154ꢁC; IR (KBr, cmꢂ1):
3377, 3256, 2964, 1621, 1576, 1455, 1370, 1186, 1100, 974,
1
872, 757, 632; H NMR (DMSO-d6): d 1.44 (s, 6H, CH3), 7.25
Acknowledgment. The authors thank the University of
Malaya for funding this study (FRGS grant No. FP009/
2008 C).
(m, 1H, indolenine-H), 7.34 (m, 1H, indolenine-H), 7.52 (d, 1H,
J ¼ 7.2 Hz, indolenine-H), 7.56 (d, 1H, J ¼ 7.6 Hz, indolenine-
H), 8.52 (s, 1H, pyrazolyl-H), 9.15 (s, 1H, pyrazolyl-H), 9.72 (s,
1H, NH2), 10.20 (s, 1H, NH2); 13C NMR (CDCl3): d 24.51,
53.30, 119.86, 120.67, 121.06, 125.98, 127.98, 130.17, 143.57,
146.40, 153.39, 176.81, 177.69; MS: m/z 271 (MHþ); Anal.
Calcd for C14H14N4S: C, 62.20; H, 5.22; N, 20.72; S, 11.86%.
Found: C, 61.86; H, 5.08; N, 20.49; S, 11.71%.
3,3-Dimethyl-2-(1H-pyrazol-4-yl)-3H-indolium thiocyanate
(9). Yield: 0.15 g, 28%. mp 177–180ꢁC; IR (KBr, cmꢂ1):
3105, 2078, 1610, 1594, 1249, 1163, 944, 761; 1H NMR
(DMSO-d6): d 1.65 (s, 6H, CH3), 7.39–7.50 (m, 2H, indole-
nine-H), 7.58 (d, 1H, J ¼ 7.3 Hz, indolenine-H), 7.74 (d, 1H,
J ¼ 7.3 Hz, indolenine-H), 8.85 (s, 2H, pyrazolyl-H); 13C
NMR (DMSO-d6): d 25.49, 53.24, 110.14, 116.28, 123.50,
128.02, 129.35, 138.64, 141.96, 143.52, 180.75, 206.72; Anal.
Calcd for C14H14N4S: C, 62.20; H, 5.22; N, 20.72; S, 11.86%.
Found: C, 61.91; H, 5.41; N, 20.42; S, 11.60%.
Reaction with thiocarbohydrazide. A mixture of the dia-
ldehyde (1; 0.43 g, 2 mmol) and thiocarbohydrazide (0.318 g,
3 mmol) in ethanol (20 mL) in the presence of acetic acid (0.5
mL) was refluxed for 4 h during which the compound 12 pre-
cipitated out. It was filtered, washed with water and ethanol,
and dried over silica gel. A Suitable crystal for X-ray analysis
was obtained by recrystallization from DMSO. Compound 11
was separated out as a yellow solid on addition of water to the
filtrate and recrystallized from ethyl acetate to give the X-ray
quality crystals.
4-(3,3-Dimethyl-3H-indol-2-yl)-pyrazole-1-carbothioic acid
hydrazide (11). Yield: 0.31 g, 54%. mp 149–150ꢁC; IR (KBr,
cmꢂ1): 3260, 2965, 1579, 1540, 1454, 1358, 1246, 1165, 1014,
896, 750; 1H NMR (CDCl3): d 1.52 (s, 6H, CH3), 4.76 (bs,
2H, NH2), 7.25–7.39 (m, 3H, indolenine-H), 7.66 (d, 1H, J
¼7.2 Hz, indolenine-H), 8.40 (s, 1H, pyrazolyl-H), 9.05 (s,
1H, pyrazolyl-H), 9.97 (bs, 1H, NH); 13C NMR (CDCl3): d
24.56, 53.31, 118.98, 120.67, 121.07, 125.95, 128.01, 130.26,
143.19, 146.38, 153.49, 174.79, 176.90; MS: m/z 286 (MHþ);
Anal. Calcd for C14H15N5S: C, 58.92; H, 5.30; N, 24.54; S,
11.24%. Found: C, 58.49; H, 5.58; N, 24.23; S, 11.09%.
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