Journal of Chemistry
Volume 2017 (2017), Article ID 3902751, 17 pages
https://doi.org/10.1155/2017/3902751

Research Article

Microwave-Assisted Synthesis of Tetrahydrocarbazole Linked 1,2-Diazoles in Aqueous-Brønsted Acid Catalytic System

Zubi Sadiq,¹ Erum Akbar Hussain,¹ Narjis Naz,¹ Ambreen Ghani,² Kausar Yasmeen,¹ and Fizzah Iqbal¹

¹Department of Chemistry, Lahore College for Women University, Lahore 54000, Pakistan
²Department of Chemistry, University of Education, D.G. Khan Campus, Dera Ghazi Khan, Pakistan

Correspondence should be addressed to Erum Akbar Hussain; erum.hussain@gmail.com

Received 5 May 2017; Accepted 23 August 2017; Published 29 October 2017

Academic Editor: Mohamed Afzal Pasha

Copyright © 2017 Zubi Sadiq et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

A new series of tetrahydrocarbazole coupled 1,2-diazoles 4/5/6(a–o) in moderate to excellent yield was synthesized successfully via multicomponent reaction approach by adopting Michael type-addition of hydrazines on in situ generated α,β-unsaturated ketones via aldol type strategy under synthetic microwave radiations and conventional heating. Structural confirmations of all the prepared compounds were achieved by spectroscopic techniques. The best results were achieved when equal amounts of water-acetic acid were used in microwave conditions in 4 minutes.

1. Introduction

Diazole ring is prominent moiety in wide range of bioactive compounds, agrochemicals, dyestuffs, photographic, and heat resistant polymers and attains distinct interest of researchers [1, 2]. Sufficient literature is available on its electronic applications as they are Intramolecular Charge Transfer (ICT) compounds and demonstrate fluorescent brightening characteristics. They possess distinct whole transport tendency in solar cells and electroluminescent devices [3]. Due to its synthetic versatility, it is one of the most important and stimulating units of high profiled molecules particularly with medicinal impact [4–7]. Moreover, 1,2-diazole having carbazole hybrids exhibit prominently enhanced material properties [8]. Tetrahydrocarbazole belongs to condensed heterocyclic system. Increasing demand of green protocols in organic synthesis provides microwave-assisted approach to environmentally undesirable procedures. Microwave mode is believed as a better lead in synthetic transformation with central usefulness such as accelerated rate of reaction, improved yield, clean setup, ecofriendly, economical, and/or high atom economy hence termed as “e-chemistry” [9]. Mostly one-pot multicomponent reactions (MCR) heteroannulation is successfully achieved on exposure to microwaves in one-pot assembly of neat reactants [10, 11].

Water as reaction solvent has become the prime choice due to ecofriendly nature [12]. This green solvent in combination with Brønsted acid like acetic acid is developed as catalytic system to afford desired 1,2-diazole entities in a benign way. This biodegradable catalytic system thus furnished mild conditions and sustainable reaction medium. In view of ongoing investigations on green protocols for preparing tetrahydrocarbazoles in our lab [13–15], we have modified conventional approach of condensation followed by Michael type-addition to obtain tetrahydrocarbazole linked 1,2-diazoles under synthetic microwave. Reaction time, yield, and purity of compounds have been compared in both processes individually. This effort is a contribution to designing innovative molecules with diverse properties in a clean and speedy way.

2. Materials and Methods

2.1. Materials

Melting points were recorded by open capillary method and are uncorrected. U-2800 Hitachi, UV-visible spectrophotometer was used for finding . KBr discs were used to record FTIR spectra on Midac Corporation FTIR spectrophotometer and values were reported in cm⁻¹. ¹H NMR spectra were measured on Bruker AXS 400 MHz spectrometer using TMS as an internal standard and DMSO- as solvent (chemical shift in δ, ppm). Mass spectra were recorded by GCMS-QP2010S Shimadzu Scientific Instruments, Inc. CHEM Discover 908010 focused microwave synthesis system was used to carry out all mentioned organic transformations. Crude products were identified on TLC (silica gel coated Al sheets, Merck 60 F₂₅₄, 0.2 mm thick) using UV light at 254/365 nm (CAMAG scientific Inc).

2.2. Synthesis

2.2.1. Tetrahydrocarbazole Linked 1,2-Diazoles Synthesis on Conventional Heating

To the solution of equimolar amount of substrate (1a/1b/1c) in dry methanol was added sodium methoxide (20 mol%) followed by addition of respective aldehydes (2a–e) (Table 1). After 30-minute reflux, hydrazine (3a/3b/3c) was added drop wise and reaction continued for further hours. When it got completed, monitored through TLC, reaction mixture was poured on crushed ice to get crude product precipitates. It was recrystallized in ethanol, chromatograph over silica (dichloromethane-methanol; 9.5 : 0.5), and yield was calculated.

Table 1: An overview of reactants and diazoles 4/5/6(a–o).

Sr #

Aldehyde
Hydrazine unit
Product code

(1)

C₆H₅  (2a)
H₂N⋅NH₂⋅H₂O (3a)
4a

(2)
o-OH-C₆H₄  (2b)
H₂N⋅NH₂⋅H₂O (3a)
4b

(3)
p-OMe-C₆H₄  (2c)
H₂N⋅NH₂⋅H₂O (3a)
4c

(4)
p-Cl-C₆H₄  (2d)
H₂N⋅NH₂⋅H₂O (3a)
4d

(5)
C₄H₃O (2e)
H₂N⋅NH₂⋅H₂O (3a)
4e

(6)
C₆H₅  (2a)
2,4-NO₂-C₆H₃  (3b)
4f

(7)
o-OH-C₆H₄  (2b)
2,4-NO₂-C₆H₃  (3b)
4g

(8)
p-OMe-C₆H₄  (2c)
2,4-NO₂-C₆H₃  (3b)
4h

(9)
p-Cl-C₆H₄  (2d)
2,4-NO₂-C₆H₃  (3b)
4i

(10)
C₄H₃O (2e)
2,4-NO₂-C₆H₃  (3b)
4j

(11)
C₆H₅  (2a)
CS(NH₂)NH⋅NH₂  (3c)
4k

(12)
o-OH-C₆H₄  (2b)
CS(NH₂)NH⋅NH₂  (3c)
4l

(13)
p-OMe-C₆H₄  (2c)
CS(NH₂)NH⋅NH₂  (3c)
4m

(14)
p-Cl-C₆H₄  (2d)
CS(NH₂)NH⋅NH₂  (3c)
4n

(15)
C₄H₃O (2e)
CS(NH₂)NH⋅NH₂  (3c)
4o

(16)

C₆H₅  (2a)
H₂N⋅NH₂⋅H₂O (3a)
5a

(17)
o-OH-C₆H₄  (2b)
H₂N⋅NH₂⋅H₂O (3a)
5b

(18)
p-OMe-C₆H₄  (2c)
H₂N⋅NH₂⋅H₂O (3a)
5c

(19)
p-Cl-C₆H₄  (2d)
H₂N⋅NH₂⋅H₂O (3a)
5d

(20)
C₄H₃O (2e)
H₂N⋅NH₂⋅H₂O (3a)
5e

(21)
C₆H₅  (2a)
2,4-NO₂-C₆H₃  (3b)
5f

(22)
o-OH-C₆H₄  (2b)
2,4-NO₂-C₆H₃  (3b)
5g

(23)
p-OMe-C₆H₄  (2c)
2,4-NO₂-C₆H₃  (3b)
5h

(24)
4-Cl-C₆H₄  (2d)
2,4-NO₂-C₆H₃  (3b)
5i

(25)
C₄H₃O (2e)
2,4-NO₂-C₆H₃  (3b)
5j

(26)
C₆H₅  (2a)
CS(NH₂)NH⋅NH₂  (3c)
5k

(27)
o-OH-C₆H₄  (2b)
CS(NH₂)NH⋅NH₂  (3c)
5l

(28)
p-OMe-C₆H₄  (2c)
CS(NH₂)NH⋅NH₂  (3c)
5m

(29)
p-Cl-C₆H₄  (2d)
CS(NH₂)NH⋅NH₂  (3c)
5n

(30)
C₄H₃O (2e)
CS(NH₂)NH⋅NH₂  (3c)
5o

(31)

C₆H₅  (2a)
H₂N⋅NH₂⋅H₂O (3a)
6a

(32)
o-OH-C₆H₄  (2b)
H₂N⋅NH₂⋅H₂O (3a)
6b

(33)
p-OMe-C₆H₄  (2c)
H₂N⋅NH₂⋅H₂O (3a)
6c

(34)
p-Cl-C₆H₄  (2d)
H₂N⋅NH₂⋅H₂O (3a)
6d

(35)
C₄H₃O (2e)
H₂N⋅NH₂⋅H₂O (3a)
6e

(36)
C₆H₅  (2a)
2,4-NO₂-C₆H₃  (3b)
6f

(37)
o-OH-C₆H₄  (2b)
2,4-NO₂-C₆H₃  (3b)
6g

(38)
p-OMe-C₆H₄  (2c)
2,4-NO₂-C₆H₃  (3b)
6h

(39)
p-Cl-C₆H₄  (2d)
2,4-NO₂-C₆H₃  (3b)
6i

(40)
C₄H₃O (2e)
2,4-NO₂-C₆H₃  (3b)
6j

(41)
C₆H₅  (2a)
CS(NH₂)NH⋅NH₂  (3c)
6k

(42)
o-OH-C₆H₄  (2b)
CS(NH₂)NH⋅NH₂  (3c)
6l

(43)
p-OMe-C₆H₄  (2c)
CS(NH₂)NH⋅NH₂  (3c)
6m

(44)
p-Cl-C₆H₄  (2d)
CS(NH₂)NH⋅NH₂  (3c)
6n

(45)
C₄H₃O (2e)
CS(NH₂)NH⋅NH₂  (3c)
6o

2.2.2. Microwave Synthesis of Tetrahydrocarbazole Linked 1,2-Diazoles

1.0 equiv of substrate (1a/1b/1c), 1.0 equiv of aromatic aldehyde (2a–e), and 1.2 equiv of respective hydrazines (3a/3b/3c) were added in water-acetic acid (1 : 1) solvent in 10 mL sealed tube and irradiated at 300 W for appropriate time (Table 2). Standard microwave protocols were followed throughout reaction. After completion of the reaction, it was concentrated in vacuum; crude product was subjected to recrystallization with methanol to get pure product.

Table 2: Summary of physical data of synthetic diazoles 4/5/6(a–o).

Entry
Product
Mol. formula
Color/state
Conventional
Microwave

Time (hr)
Yield (%)
Time (min)
Yield (%)

(1)

Yellowish green solid
5
68
4
68

(2)

Yellowish green solid
6
72
5
72

(3)

Yellowish green solid
5
82
5
83

(4)

Yellowish green solid
6
79
6
79

(5)

Yellowish green solid
4.5
80
6
80

(6)

Yellowish green solid
4.5
71
7
71

(7)

Yellowish green solid
5.5
84
5
82

(8)

Yellowish green solid
4
83
4
83

(9)

Yellowish green solid
5
77
6
77

(10)

Yellowish green solid

84
6
81

(11)

Yellowish green solid

75
6
75

(12)

Yellowish green solid
5.5
73
6
73

(13)

Yellowish green solid
6.0
85
5
85

(14)

Yellowish green solid
6.5
87
6
87

(15)

Yellowish green solid
4.5
73
5
79

(16)

Reddish orange solid
5
76
6
76

(17)

Reddish orange solid
5.5
75
6
75

(18)

Reddish orange solid
4.5
78
5
78

(19)

Reddish orange solid
5
84
5
84

(20)

Reddish orange solid
5
84
6
84

(21)

Reddish orange solid
4.75
74
5
74

(22)

Reddish orange solid
6.5
75
6
75

(23)

Reddish orange solid
5.75
84
6
84

(24)

Reddish orange solid
5
78
5
78

(25)

Reddish orange solid
4.5
80
5
80

(26)

Reddish orange solid
6.5
75
6
75

(27)

Reddish orange solid
6
78
5
78

(28)

Reddish orange solid
5.5
79
7
79

(29)

Reddish orange solid
6
84
6
84

(30)

Reddish orange solid
5.5
82
7
82

(31)

Yellow solid
2.5
75
5
88

(32)

Yellow solid
3.5
62
7
85

(33)

Yellow solid
3.75
65
8
79

(34)

Yellow solid
3.5
60
6
86

(35)

Yellow solid
4
65
8
78

(36)

Yellowish brown gummy
3.75
24
6
76

(37)

Reddish brown gummy
5.5
31
6
75

(38)

Reddish brown solid
6
39
5
78

(39)

Dark brown solid
6.25
33
5
84

(40)

Reddish brown solid
5
36
6
80

(41)

Brownish Yellow solid
5.5
66
8
81

(42)

Reddish yellow solid
4.75
63
5
82

(43)

Yellow solid
5
64
7
84

(44)

Yellow solid
5.5
59
7
75

(45)

Yellow solid
5.25
62
9
86

2,3,4,9-Tetrahydro-1-(4,5-dihydro-5-phenyl-1H-pyrazol-3-yl)-1H-carbazole (4a). FTIR (KBr) cm⁻¹: 1578 (C=C), 1643 (C=N), 1043 (C-N), 2984 (C-H), 3064 (N-H); ¹H NMR (-DMSO) δ: 10.33 (1H, s, H-9), 7.85–7.52 (5H, m, Ph), 7.48–7.32 (4H, m, Ph), 6.21 (1H, s, N-H pyra), 4.81 (1H, m, ), 3.68 (1H, dd, = 18, 10 Hz, ), 3.43 (1H, dd, = 18, 10 Hz, ), 1.85–1.76 (7H m, Cyclo). MS (EI): = 315.174 [M]⁺.

2-(4,5-Dihydro-3-(6,7,8,9-tetrahydro-5H-carbazol-8-yl)-1H-pyrazol-5-yl)phenol (4b). FTIR (KBr) cm⁻¹: 1575 (C=C), 1642 (C=N), 1044 (C-N), 3061 (N-H), 1435 (O-H), 2982 (C-H); ¹H NMR (-DMSO) δ: 10.35 (1H, s, H-9), 7.84–7.53 (4H, m, Ph), 7.45–7.34 (4H, m, Ph), 6.25 (1H, s, N-H pyra), 4.84 (1H, m, ), 3.63 (1H, dd, = 18, 10 Hz, ), 3.45 (1H, dd, = 18, 10 Hz, ), 1.82–1.74 (7H m, Cyclo). MS (EI): = 331.168 [M]⁺.

2,3,4,9-Tetrahydro-1-(4,5-dihydro-5-(4-methoxyphenyl)-1H-pyrazol-3-yl)-1H-carbazole (4c). FTIR (KBr) cm⁻¹: 1577 (C=C), 1640 (C=N), 1047 (C-N), 3059 (N-H), 2987 (C-H), 1100 (C-OCH₃). ¹H NMR (-DMSO) δ: 10.38 (1H, s, H-9), 7.86–7.44 (4H, m, Ph), 7.52–7.41 (4H, m, Ph), 6.26 (1H, s, N-H pyra), 4.82 (1H, m, ), 3.64 (1H, dd, = 18, 10 Hz, ), 3.46 (1H, dd, = 18, 10 Hz, ), 3.14 (3H, s, OCH₃), 1.80–1.72 (7H m, Cyclo). MS (EI): = 345.184 [M]⁺.

1-(5-(4-Chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2,3,4,9-tetrahydro-1H-carbazole (4d). FTIR (KBr) cm⁻¹: 1575 (C=C), 1638 (C=N), 1044 (C-N), 3064 (N-H), 2990 (C-H), 735 (C-Cl). ¹H NMR (-DMSO) δ: 10.35 (1H, s, H-9), 7.84–7.53 (4H, m, Ph), 7.45–7.34 (4H, m, Ph), 6.25 (1H, s, N-H pyra), 4.85 (1H, m, ), 3.63 (1H, dd, = 18, 10 Hz, ), 3.45 (1H, dd, = 18, 10 Hz, ), 1.82–1.74 (7H m, Cyclo). MS (EI): = 349.135 [M]⁺.

1-(5-(Furan-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)-2,3,4,9-tetrahydro-1H-carbazole (4e). FTIR (KBr) cm⁻¹: 1572 (C=C), 1648 (C=N), 1045 (C-N), 3067 (N-H), 2994 (C-H), 1160 (C-O); ¹H NMR (-DMSO) δ: 10.34 (1H, s, H-9), 7.88–7.73 (3H, m, Ph), 7.47–7.38 (4H, m, Ph), 6.27 (1H, s, N-H pyra), 4.83 (1H, m, ), 3.65 (1H, dd, = 18, 10 Hz, ), 3.48 (1H, dd, = 18, 10 Hz, ), 1.86–1.78 (7H m, Cyclo). MS (EI): = 305.153 [M]⁺.

2,3,4,9-Tetrahydro-1-(4,5-dihydro-1-(2,4-dinitrophenyl)-5-phenyl-1H-pyrazol-3-yl)-1H-carbazole (4f). FTIR (KBr) cm⁻¹: 1577 (C=C), 1640 (C=N), 1047 (C-N), 2987 (C-H), 1450 (C-NO₂). ¹H NMR (-DMSO) δ: 10.35 (1H, s, H-9), 8.30 (1H, dd, = 8.8, 2.3 Hz, H-5DNPh), 7.84–7.53 (5H, m, Ph), 7.69 (1H, d, = 8.8 Hz, H-6 DNPh), 7.61 (1H, d, = 2.3 Hz, H-3DNPh), 7.45–7.34 (4H, m, Ph), 4.81 (1H, m, ), 3.63 (1H, dd, = 18, 10 Hz, ), 3.45 (1H, dd, = 18, 10 Hz, ), 1.82–1.74 (7H m, Cyclo). MS (EI): = 481.175 [M]⁺.

2-(4,5-Dihydro-3-(6,7,8,9-tetrahydro-5H-carbazol-8-yl)-1-(2,4-dinitrophenyl)-1H-pyrazol-5-yl)phenol (4g). FTIR (KBr) cm⁻¹: 1574 (C=C), 1638 (C=N), 1049 (C-N), 2987 (C-H), 3300 (C-OH), 1398 (C-NO₂). ¹H NMR (-DMSO) δ: 10.32 (1H, s, H-9), 8.27 (1H, dd, = 8.8, 2.3 Hz, H-5DNPh), 7.80–7.48 (5H, m, Ph), 7.67 (1H, d, = 8.8 Hz, H-6DNPh), 7.58 (1H, d, = 8.8 Hz, H-3DNPh), 7.41–7.30 (4H, m, Ph), 4.84 (1H, m, ), 3.54 (1H, dd, = 18, 10 Hz, ), 3.41 (1H, dd, = 18, 10 Hz, ), 1.79–1.38 (7H m, Cyclo). MS (EI): = 349.135 [M]⁺.

2,3,4,9-Tetrahydro-1-(4,5-dihydro-5-(4-methoxyphenyl)-1-(2,4-dinitrophenyl)-1H-pyrazol-3-yl)-1H-carbazole (4h). FTIR (KBr) cm⁻¹: 1578 (C=C), 1640 (C=N), 1049 (C-N), 2989 (C-H), 1545 (C-NO₂), 1101 (C-OCH₃). ¹H NMR (-DMSO) δ: 10.34 (1H, s, H-9), 8.27 (1H, dd, = 8.8, 2.3 Hz, H-5 DNPh), 7.79–7.46 (5H, m, Ph), 7.61 (1H, d, = 8.8 Hz, H-6 DNPh), 7.53 (1H, d, = 2.3 Hz, H-3 DNPh), 7.39–7.27 (4H, m, THCz), 4.82 (1H, m, ), 3.56 (1H, dd, = 18, 10 Hz, ), 3.38 (1H, dd, = 18, 10 Hz, ), 3.15 (3H, s, OCH₃), 1.77–1.67 (7H m, Cyclo). MS (EI): 511.186 [M]⁺.

1-(5-(4-Chlorophenyl)-4,5-dihydro-1-(2,4-dinitrophenyl)-1H-pyrazol-3-yl)-2,3,4,9-tetrahydro-1H-carbazole (4i). FTIR (KBr) cm⁻¹: 1577 (C=C), 1648 (C=N), 1048 (C-N), 2990 (C-H), 1547 (C-NO₂), 1101 (C-Cl). ¹H NMR (-DMSO) δ: 10.31 (1H, s, H-9), 8.26 (1H, dd, = 8.8, 2.3 Hz, H-5DNPh), 7.74–7.58 (5H, m, Ph), 7.47 (1H, d, = 8.8 Hz, H-6 DNPh), 7.56 (1H, d, = 2.3 Hz, H-3 DNPh), 7.41–7.30 (4H, m, THCz), 4.82 (1H, m, ), 3.58 (1H, dd, = 18, 10 Hz, ), 3.41 (1H, dd, = 18, 10 Hz, ), 1.81–1.72 (7H m, Cyclo). MS (EI): = 515.136 [M]⁺.

1-(5-(Furan-2-yl)-4,5-dihydro-1-(2,4-dinitrophenyl)-1H-pyrazol-3-yl)-2,3,4,9-tetrahydro-1H-carbazole (4j). FTIR (KBr) cm⁻¹: 1579 (C=C), 1640 (C=N), 1053 (C-N), 2997 (C-H), 1550 (C-NO₂), 1159 (C-O-C). ¹H NMR (-DMSO) δ: 10.35 (1H, s, H-9), 8.30 (1H, dd, = 8.8, 2.3 Hz, H-5 DNPh), 7.79–7.48 (3H, m, Ph), 7.64 (1H, d, = 8.8 Hz, H-6 DNPh), 7.55 (1H, d, = 2.3 Hz, H-3 DNPh), 7.41–7.29 (4H, m, THCz), 4.84 (1H, m, ), 3.58 (1H, dd, = 18, 10 Hz, ), 3.40 (1H, dd, = 18, 10 Hz, ), 1.78–1.67 (7H m, Cyclo). MS (EI): = 471.154 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-5H-carbazol-8-yl)-5-phenylpyrazole-1-carbothioamide (4k). FTIR (KBr) cm⁻¹: 1578 (C=C), 1640 (C=N), 1049 (C-N), 2989 (C-H), 3605 (C-NH₂), 1208 (C=S). ¹H NMR (-DMSO) δ: 10.29 (1H, s, H-9), 7.77–7.48 (5H, m, Ph), 7.38–7.27 (4H, m, THCz), 4.85 (1H, m, ), 3.57 (1H, d, = 18, 10 Hz, ), 3.42 (1H, d, = 18, 10 Hz, ), 1.80–1.72 (7H m, Cyclo). MS (EI): = 497.170 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-5H-carbazol-8-yl)-5-(2-hydroxyphenyl)pyrazole-1-carbothioamide (4l). FTIR (KBr) cm⁻¹: 1579 (C=C), 1635 (C=N), 1054 (C-N), 2979 (C-H), 3300 (C-OH), 3598 (C-NH₂), 1200 (C=S). ¹H NMR (-DMSO) δ: 10.33 (1H, s, H-9), 7.81–7.48 (4H, m, Ph), 7.41–7.29 (4H, m, THCz), 4.81 (1H, m, ), 3.59 (1H, dd, = 18, 10 Hz, ), 3.41 (1H, dd, = 18, 10 Hz, ), 1.78–1.70 (7H m, Cyclo). MS (EI): = 390.151 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-5H-carbazol-8-yl)-5-(4-methoxyphenyl)pyrazole-1-carbothioamide (4m). FTIR (KBr) cm⁻¹: 1579 (C=C), 1640 (C=N), 1053 (C-N), 2997 (C-H), 1101 (C-OCH₃), 3599 (C-NH₂), 1201 (C=S). ¹H NMR (-DMSO) δ: 10.29 (1H, s, H-9), 7.78–7.49 (4H, m, Ph), 7.38–7.27 (4H, m, THCz), 4.84 (1H, m, ), 3.57 (1H, dd, = 18, 10 Hz, ), 3.39 (1H, dd, = 18, 10 Hz, ), 3.11 (3H, s, OCH₃), 1.78–1.71 (7H m, Cyclo). MS (EI): = 404.167 [M]⁺.

5-(4-Chlorophenyl)-4,5-dihydro-3-(6,7,8,9-tetrahydro-5H-carbazol-8-yl)pyrazole-1-carbothioamide (4n). FTIR (KBr) cm⁻¹: 1582 (C=C), 1635 (C=N), 1051 (C-N), 2987 (C-H), 740 (C-Cl), 3595 (C-NH₂), 1200 (C=S). ¹H NMR (-DMSO) δ: 10.31 (1H, s, H-9), 7.82–7.50 (4H, m, Ph), 7.42–7.29 (4H, m, THCz), 4.80 (1H, m, ), 3.60 (1H, dd, = 18, 10 Hz, ), 3.42 (1H, dd, = 18, 10 Hz, ), 1.80–1.68 (7H m, Cyclo). MS (EI): = 408.118 [M]⁺.

5-(Furan-2-yl)-4,5-dihydro-3-(6,7,8,9-tetrahydro-5H-carbazol-8-yl)pyrazole-1-carbothioamide (4o). FTIR (KBr) cm⁻¹: 1579 (C=C), 1640 (C=N), 1053 (C-N), 2997 (C-H), 1159 (C-O-C), 3598 (C-NH₂), 1200 (C=S). ¹H NMR (-DMSO) δ: 10.34 (1H, s, H-9), 7.85–7.55 (3H, m, Ph), 7.48–7.37 (4H, m, THCz), 4.85 (1H, m, ), 3.66 (1H, dd, = 18, 10 Hz, ), 3.49 (1H, dd, = 18, 10 Hz, ), 1.85–1.79 (7H m, Cyclo). MS (EI): = 364.136 [M]⁺.

2,3,4,9-Tetrahydro-1-(4,5-dihydro-5-phenyl-1H-pyrazol-3-yl)-6-nitro-1H-carbazole (5a). FTIR (KBr) cm⁻¹: 1574 (C=C), 1638 (C=N), 1049 (C-N), 3056 (N-H), 2987 (C-H), 1540 (C-NO₂). ¹H NMR (-DMSO) δ: 10.86 (1H, s, H-9), 8.20 (1H, dd, = 8.8, 2.3 Hz, H-7NO₂THCz), 7.68 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.47–7.38 (5H, m, Ph), 7.23 (1H, d, = 2.3 Hz, H-5 NO₂-THCz), 6.34 (s, 1H, N-H pyra), 5.33 (1H, m, ), 3.55 (1H, dd, = 18, 12 Hz, ), 3.21 (1H, dd, = 18, 12 Hz, ), 1.75–1.67 (m, 7H, Cyclo). MS (EI): = 360.159 [M]⁺.

2-(4,5-Dihydro-3-(6,7,8,9-tetrahydro-3-nitro-5H-carbazol-8-yl)-1H-pyrazol-5-yl)phenol (5b). FTIR (KBr) cm⁻¹: 1572 (C=C), 1630 (C=N), 1043 (C-N), 3054 (N-H), 298 (C-H), 3300 (C-OH), 1551 (C-NO₂). ¹H NMR (-DMSO) δ: 10.63 (1H, s, H-9), 8.26 (1H, dd, = 8.8, 2.3 Hz, H-7NO₂THCz), 7.68 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.52–7.41 (4H, m, Ph), 7.25 (1H, d, = 2.3 Hz, H-5 NO₂-THCz), 6.37 (s, 1H, N-Hpyra), 5.38 (1H, m, ), 3.58 (1H, dd, = 18, 12 Hz, ), 3.25 (1H, dd, = 18, 12 Hz, ), 1.78–1.69 (m, 7H, Cyclo). MS (EI): = 376.154 [M]⁺.

2,3,4,9-Tetrahydro-1-(4,5-dihydro-5-(4-methoxyphenyl)-1H-pyrazol-3-yl)-6-nitro-1H-carbazole (5c). FTIR (KBr) cm⁻¹: 1574 (C=C), 1638 (C=N), 1049 (C-N), 3056 (N-H), 2987 (C-H), 1100 (C-OCH₃), 1549 (C-NO₂). ¹H NMR (-DMSO) δ: 10.62 (1H, s, H-9), 8.26 (1H, dd, = 8.8, 2.3 Hz, H-7NO₂THCz), 7.68 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.47–7.34 (4H, m, Ph), 7.22 (1H, d, = 2.1 Hz, H-5 NO₂THCz), 6.36 (s, 1H, N-Hpyra), 5.38 (1H, m, ), 3.52 (1H, dd, = 18, 12 Hz, ), 3.29 (1H, dd, = 18, 12 Hz, ), 3.12 (3H, s, OCH₃), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 390.169 [M]⁺.

1-(5-(4-Chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2,3,4,9-tetrahydro-6-nitro-1H-carbazole (5d). FTIR (KBr) cm⁻¹: 1574 (C=C), 1638 (C=N), 1049 (C-N), 3056 (N-H), 2987 (C-H), 730 (C-Cl), 1550 (C-NO₂). ¹H NMR (-DMSO) δ: 10.69 (1H, s, H-9), 8.26 (1H, dd, = 8.4, 2.1 Hz, H-7NO₂THCz), 7.68 (1H, d, = 8.4 Hz, H-8 NO₂THCz), 7.47–7.35 (4H, m, Ph), 7.22 (1H, d, = 2.1 Hz, H-5 NO₂THCz), 6.32 (s, 1H, N-Hpyra), 5.26 (m, 1H, ), 3.54 (1H, dd, = 18, 12 Hz, ), 3.27 (1H, dd, = 18, 12 Hz, ), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 390.120 [M]⁺.

1-(5-(Furan-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)-2,3,4,9-tetrahydro-6-nitro-1H-carbazole (5e). FTIR (KBr) cm⁻¹: 1578 (C=C), 1645 (C=N), 1054 (C-N), 3045 (N-H), 2985 (C-H), 1164 (C-O-C), 1339 (C-NO₂). ¹H NMR (-DMSO) δ: 10.69 (1H, s, H-9), 8.26 (1H, dd, = 8.8, 2.3 Hz, H-7NO₂THCz), 7.68 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.44–7.31 (3H, m, Ph), 7.22 (1H, d, = 2.3 Hz, H-5 NO₂THCz), 6.34 (s, 1H, N-Hpyra), 5.27 (1H, m, ), 3.52 (1H, dd, = 18, 12 Hz, ), 3.25 (1H, dd, = 18, 12 Hz, ), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 350.138 [M]⁺.

2,3,4,9-Tetrahydro-1-(4,5-dihydro-1-(2,4-dinitrophenyl)-5-phenyl-1H-pyrazol-3-yl)-6-nitro-1H-carbazole (5f). FTIR (KBr) cm⁻¹: 1574 (C=C), 1639 (C=N), 1056 (C-N), 3046 (N-H), 2987 (C-H), 1550 (C-NO₂). ¹H NMR (-DMSO) δ: 10.68 (1H, s, H-9), 8.34 (1H, dd, = 8.8, 2.3 Hz, H-7 NO₂THCz), 8.28 (1H, d, = 2.3 Hz, H-5 NO₂THCz), 7.67 (1H, d, = 8.8 Hz, H-5 DNPh), 7.58 (1H, d, = 8.8 Hz, H-5DNTHCz), 7.49–7.37 (5H, m, Ph), 7.18 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.12 (1H, d, = 2.3 Hz, H-3DNPh), 5.24 (1H, m, ), 3.53 (1H, dd, = 18, 12 Hz, ), 3.29 (1H, dd, = 18, 12 Hz, ), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 526.160 [M]⁺.

2-(4,5-Dihydro-3-(6,7,8,9-tetrahydro-3-nitro-5H-carbazol-8-yl)-1-(2,4-dinitrophenyl)-1H-pyrazol-5-yl)phenol (5g). FTIR (KBr) cm⁻¹: 1569 (C=C), 1640 (C=N), 1049 (C-N), 2987 (C-H), 3400 (C-OH), 1445 (C-NO₂). ¹H NMR (-DMSO) δ: 10.76 (1H, s, H-9), 8.33 (1H, dd, = 8.8, 2.1 Hz, H-5 DNPh), 8.28 (1H, dd, = 8.8, 2.3 Hz, H-7 NO₂THCz), 7.62 (1H, d, = 8.8 Hz, H-6 DNPh), 7.55 (1H, dd, = 8.8 Hz, H-3 DNPh), 7.46–7.34 (4H, m, Ph), 7.24 (1H, d, = 2.3 Hz, H-5, NO₂THCz), 7.15 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 5.18 (1H, m, ), 3.45 (1H, dd, = 18, 12 Hz, ), 3.21 (1H, dd, = 18, 12 Hz, ), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 542.155 [M]⁺.

2,3,4,9-Tetrahydro-1-(4,5-dihydro-5-(4-methoxyphenyl)-1-(2,4-dinitrophenyl)-1H-pyrazol-3-yl)-6-nitro-1H-carbazole (5h). FTIR (KBr) cm⁻¹: 1578 (C=C), 1644 (C=N), 1044 (C-N), 2980 (C-H), 1058 (C-OCH₃), 1354 (C-NO₂). ¹H NMR (-DMSO) δ: 10.44 (1H, s, H-9), 8.35 (1H, dd, = 8.8, 2.3 Hz, H-7 NO₂THCz), 8.27 (1H, d, = 2.3 Hz, H-5 NO₂THCz), 7.57 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.49 (1H, dd, = 8.8, 2.1 Hz, H-5 DNPh), 7.41–7.32 (4H, m, Ph), 7.11 (1H, d, = 8.8, 2.1 Hz, H-6 DNPh), 6.92 (1H, d, = 2.3 Hz, H-3 DNPh), 5.25 (1H, m, ), 3.47 (1H, dd, = 18, 12 Hz, ), 3.20 (1H, dd, = 18, 12 Hz, ), 3.08 (3H, s, OCH₃), 1.72–1.58 (m, 7H, Cyclo). MS (EI): = 556.171 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-3-nitro-5H-carbazol-8-yl)-5-(2-hydroxyphenyl)pyrazole-1-carbothioamide (5i). FTIR (KBr) cm⁻¹: 1574 (C=C), 1646 (C=N), 1055 (C-N), 2987 (C-H), 745 (C-Cl), 1450 (C-NO₂). ¹H NMR (-DMSO) δ: 10.54 (1H, s, H-9), 8.32 (1H, dd, = 8.9, 2.1 Hz, H-7 NO₂THCz), 8.26 (1H, d, = 2.1 Hz, H-5NO₂THCz), 7.66 (1H, d, = 8.9, 2.4 Hz, H-5 DNPh), 7.56 (1H, d, = 8.9 Hz, H-8 NO₂THCz), 7.44–7.32 (4H, m, Ph), 7.28 (1H, d, = 2.3 Hz, H-3, DNPh), 7.18 (1H, d, = 8.9 Hz, H-6 DNPh), 5.34 (1H, m, ), 3.52 (1H, dd, = 18, 12 Hz, ), 3.29 (1H, dd, = 18, 12 Hz, ), 3.12 (3H, s, OCH₃), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 560.121 [M]⁺.

1-(5-(Furan-2-yl)-4,5-dihydro-1-(2,4-dinitrophenyl)-1H-pyrazol-3-yl)-2,3,4,9-tetrahydro-6-nitro-1H-carbazole (5j). FTIR (KBr) cm⁻¹: 1569 (C=C), 1637 (C=N), 1049 (C-N), 2980 (C-H), 1164 (C-O-C), 1490 (C-NO₂). ¹H NMR (-DMSO) δ: 10.42 (1H, s, H-9), 8.30 (1H, dd, = 8.9, 2.1 Hz, H-7 NO₂THCz), 8.28 (1H, d, = 2.1 Hz, H-5 NO₂THCz), 7.69 (1H, dd, = 8.9, 2.1 Hz, H-5 DNPh), 7.61 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.23 (1H, d, = 2.3 Hz, H-3, DNPh), 7.16 (1H, d, = 2.3 Hz, H-6 DNPh), 5.28 (1H, m, ), 3.54 (1H, dd, = 18, 12 Hz, ), 3.31 (1H, dd, = 18, 12 Hz, ), 1.78–1.69 (m, 7H, Cyclo). MS (EI): = 516.139 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-3-nitro-5H-carbazol-8-yl)-5-phenylpyrazole-1-carbothioamide (5k). FTIR (KBr) cm⁻¹: 1572 (C=C), 1630 (C=N), 1043 (C-N), 2980 (C-H), 3587 (C-NH₂), 1200 (C=S), 1490 (C-NO₂). ¹H NMR (-DMSO) δ: 10.49 (1H, s, H-9), 8.11 (1H, dd, = 8.8, 2.3 Hz, H-7NO₂THCz), 7.62 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.41–7.34 (5H, m, Ph), 7.24 (1H, d, = 2.3 Hz, H-5 NO₂THCz), 5.22 (1H, m, ), 3.37 (1H, dd, = 18, 12 Hz, ), 3.18 (1H, dd, = 18, 12 Hz, ), 1.73–1.67 (m, 7H, Cyclo). MS (EI): = 419.142 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-3-nitro-5H-carbazol-8-yl)-5-(2-hydroxyphenyl)pyrazole-1-carbothioamide (5l). FTIR (KBr) cm⁻¹: 1568 (C=C), 1625 (C=N), 1039 (C-N), 2979 (C-H), 3300 (C-OH), 3604 (C-NH₂), 1500 (C-NO₂), 1202 (C=S). ¹H NMR (-DMSO) δ: 10.55 (1H, s, H-9), 8.15 (1H, dd, = 8.8, 2.3 Hz, H-7 NO₂THCz), 7.58 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.37–7.28 (5H, m, Ph), 7.19 (1H, d, = 2.3 Hz, H-5 NO₂THCz), 5.21 (1H, m, ), 3.32 (1H, dd, = 18, 12 Hz, ), 3.14 (1H, dd, = 18, 12 Hz, ), 1.69–1.43 (m, 7H, Cyclo). MS (EI): = 435.137 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-3-nitro-5H-carbazol-8-yl)-5-(4-methoxyphenyl)pyrazole-1-carbothioamide (5m). FTIR (KBr) cm⁻¹: 1578 (C=C), 1640 (C=N), 1049 (C-N), 2989 (C-H), 3592 (C-NH₂), 1535 (C-NO₂), 1204 (C=S), 1058 (C-OCH₃). ¹H NMR (-DMSO) δ: 10.57 (1H, s, H-9), 8.13 (1H, dd, = 8.8, 2.3 Hz, H-7 NO₂THCz), 7.49 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.31–7.17 (5H, m, Ph), 7.08 (1H, d, = 2.3 Hz, H-5 NO₂THCz), 5.24 (1H, m, ), 3.30 (1H, d, = 18, 12 Hz, ), 3.21 (1H, d, = 18, 12 Hz, ), 3.08 (3H, s, OCH₃), 1.65–1.46 (m, 7H, Cyclo). MS (EI): = 449.152 [M]⁺.

5-(4-Chlorophenyl)-4,5-dihydro-3-(6,7,8,9-tetrahydro-3-nitro-5H-carbazol-8-yl)pyrazole-1-carbothioamide (5n). FTIR (KBr) cm⁻¹: 1578 (C=C), 1640 (C=N), 1049 (C-N), 2987 (C-H), 3480 (C-NH₂), 1490 (C-NO₂), 1200 (C=S), 725 (C-Cl). ¹H NMR (-DMSO) δ: 10.42 (1H, s, H-9), 8.13 (1H, dd, = 8.8, 2.3 Hz, H-7 NO₂THCz), 7.64 (1H, d, = 8.8 Hz, H-8 NO₂-THCz), 7.47–7.29 (5H, m, Ph), 7.35 (1H, d, = 2.3 Hz, H-5 NO₂THCz), 5.19 (1H, m, ), 3.38 (1H, dd, = 18, 12 Hz, ), 3.19 (1H, dd, = 18, 12 Hz, ), 1.75–1.58 (m, 7H, Cyclo). MS (EI): = 453.103 [M]⁺.

5-(Furan-2-yl)-4,5-dihydro-3-(6,7,8,9-tetrahydro-3-nitro-5H-carbazol-8-yl)pyrazole-1-carbothioamide (5o). FTIR (KBr) cm⁻¹: 1578 (C=C), 1640 (C=N), 1049 (C-N), 2987 (C-H), 3595 (C-NH₂), 1148 (C-O-C), 1537 (C-NO₂), 1200 (C=S). ¹H NMR (-DMSO) δ: 10.38 (1H, s, H-9), 7.98 (1H, dd, = 8.8, 2.3 Hz, H-7 NO₂THCz), 7.52 (1H, d, = 8.8 Hz, H-8 NO₂THCz), 7.35–7.21 (5H, m, Ph), 7.17 (1H, d, = 2.3 Hz, H-5 NO₂THCz), 5.25 (1H, m, ), 3.58 (1H, dd, = 18, 12 Hz, ), 3.29 (1H, dd, = 18, 12 Hz, ), 1.55–1.38 (m, 7H, Cyclo). MS (EI): = 409.121 [M]⁺.

6,7,8,9-Tetrahydro-8-(4,5-dihydro-5-phenyl-1H-pyrazol-3-yl)-1,3-dinitro-5H-carbazole (6a). FTIR (KBr) cm⁻¹: 1576 (C=C), 1639 (C=N), 1045 (C-N), 3069 (N-H), 2998 (C-H), 1550 (C-NO₂). ¹H NMR (-DMSO) δ: 10.52 (1H, s, H-9), 8.31 (1H, d, = 2.3 Hz, H-7 DNTHCz), 7.52 (1H, d, = 2.3 Hz, H-5 DNTHCz), 7.38–7.31 (5H, m, Ph), 6.20 (1H, s, N-H Pyra), 5.15 (1H, m, ), 3.53 (1H, dd, = 18, 9.6 Hz, ), 3.26 (1H, dd, = 18, 9.6 Hz, ), 1.72–1.61 (m, 7H, Cyclo). MS (EI): = 405.144 [M]⁺.

2-(4,5-Dihydro-3-(6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazol-8-yl)-1H-pyrazol-5-yl)phenol (6b). FTIR (KBr) cm⁻¹: 1576 (C=C), 1637 (C=N), 1044 (C-N), 3068 (N-H), 2996 (C-H), 3329 (C-OH), 1495 (C-NO₂). ¹H NMR (-DMSO) δ: 10.53 (1H, s, H-9), 8.28 (1H, d, = 2.3 Hz, H-7 DNTHCz), 7.53 (1H, d, = 2.3 Hz, H-5 DNTHCz), 7.38–7.29 (4H, m, Ph), 6.22 (1H, s, N-H Pyra), 5.18 (1H, m, ), 3.48 (1H, dd, = 18, 9.6 Hz, ), 3.25 (1H, dd, = 18, 9.6 Hz, ), 1.71–1.63 (m, 7H, Cyclo). MS (EI): = 421.139 [M]⁺.

6,7,8,9-Tetrahydro-8-(4,5-dihydro-5-(4-methoxyphenyl)-1H-pyrazol-3-yl)-1,3-dinitro-5H-carbazole (6c). FTIR (KBr) cm⁻¹: 1578 (C=C), 1640 (C=N), 1043 (C-N), 3069 (N-H), 2998 (C-H), 1100 (C-OCH₃), 1500 (C-NO₂). ¹H NMR (-DMSO) δ: 10.54 (1H, s, H-9), 8.32 (1H, d, = 2.3 Hz, H-7 DNTHCz), 7.56 (1H, d, = 2.3 Hz, H-5 DNTHCz), 7.41–7.34 (5H, m, Ph), 6.21 (1H, s, N-H Pyra), 5.21 (1H, m, ), 3.52 (1H, dd, = 18, 9.6 Hz, ), 3.29 (1H, dd, = 18, 9.7 Hz, ), 3.14 (3H, s, OCH₃), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 435.154 [M]⁺.

8-(5-(4-Chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazole (6d). FTIR (KBr) cm⁻¹: 1574 (C=C), 1639 (C=N), 1042 (C-N), 3070 (N-H), 2996 (C-H), 740 (C-Cl) 1498 (C-NO₂). ¹H NMR (-DMSO) δ: 10.52 (1H, s, H-9), 8.31 (1H, d, = 2.4 Hz, H-7 DNTHCz), 7.67 (1H, d, = 2.4 Hz, H-5 DNTHCz), 7.44–7.38 (4H, m, Ph), 6.24 (1H, s, N-H Pyra), 4.95 (1H, m, ), 3.56 (1H, dd, = 18, 9.8 Hz, ), 3.32 (1H, dd, = 18, 9.8 Hz, ), 1.77–1.68 (m, 7H, Cyclo). MS (EI): = 439.105 [M]⁺.

8-(5-(Furan-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)-6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazole (6e). FTIR (KBr) cm⁻¹: 1567 (C=C), 1646 (C=N), 1048 (C-N), 3078 (N-H), 2988 (C-H), 1145 (C-O-C), 1437 (C-NO₂). ¹H NMR (-DMSO) δ: 10.54 (1H, s, H-9), 8.32 (1H, d, = 2.3 Hz, H-7 DNTHCz), 7.56 (1H, d, = 2.3 Hz, H-5 DNTHCz), 7.41–7.34 (3H, m, Ph), 6.21 (1H, s, N-H Pyra), 4.81 (1H, m, ), 3.52 (1H, dd, = 18, 9.6 Hz, ), 3.29 (1H, dd, = 18, 9.6 Hz, ), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 395.123 [M]⁺.

6,7,8,9-Tetrahydro-8-(4,5-dihydro-1-(2,4-dinitrophenyl)-5-phenyl-1H-pyrazol-3-yl)-1,3-dinitro-5H-carbazole (6f). FTIR (KBr) cm⁻¹: 1570 (C=C), 1645 (C=N), 1046 (C-N), 2990 (C-H), 1550 (C-NO₂). ¹H NMR (-DMSO) δ: 10.51 (1H, s, H-9), 8.26 (1H, d, = 2.1 Hz, H-7 DNTHCz), 7.62 (1H, d, = 8.9, 2.6 Hz, H-5 DNPh), 7.48 (1H, d, = 2.1 Hz, H-5 DNTHCz), 7.41 (1H, d, = 8.9 Hz, H-6 DNPh), 7.34–7.21 (5H, m, Ph), 7.45 (1H, d, = 2.6 Hz, H-3 DNPh), 4.89 (1H, m, ), 3.47 (1H, dd, = 18, 9.6 Hz, ), 3.23 (1H, dd, = 18, 9.8 Hz, ), 1.72–1.58 (m, 7H, Cyclo). MS (EI): = 571.145 [M]⁺.

2-(4,5-Dihydro-3-(6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazol-8-yl)-1-(2,4-dinitrophenyl)-1H-pyrazol-5-yl)phenol (6g). FTIR (KBr) cm⁻¹: 1576 (C=C), 1648 (C=N), 1045 (C-N), 2998 (C-H), 3329 (C-OH), 1447 (C-NO₂). ¹H NMR (-DMSO) δ: 10.48 (1H, s, H-9), 8.27 (1H, d, = 2.1 Hz, H-7 DNTHCz), 7.57 (1H, dd, = 8.1, 2.6 Hz, H-5 DNPh), 7.46 (1H, d, = 2.1 Hz, H-5 DNTHCz), 7.35 (1H, d, = 8.1 Hz, H-6 DNPh), 7.27–7.18 (4H, m, Ph), 7.11 (1H, d, = 2.6 Hz, H-3 DNPh), 4.87 (1H, m, ), 3.48 (1H, dd, = 18, 9.6 Hz, ), 3.26 (1H, dd, = 18, 9.6 Hz, ), 1.75–1.61 (m, 7H, Cyclo). MS (EI): = 587.140 [M]⁺.

6,7,8,9-Tetrahydro-8-(4,5-dihydro-5-(4-methoxyphenyl)-1-(2,4-dinitrophenyl)-1H-pyrazol-3-yl)-1,3-dinitro-5H-carbazole (6h). FTIR (KBr) cm⁻¹: 1568 (C=C), 1645 (C=N), 1048 (C-N), 2995 (C-H), 1170 (C-OCH₃), 1449 (C-NO₂). ¹H NMR (-DMSO) δ: 10.47 (1H, s, H-9), 8.27 (1H, d, = 2.1 Hz, H-7 DNTHCz), 7.59 (1H, dd, = 8.1, 2.6 Hz, H-5 DNPh), 7.47 (1H, d, = 2.1 Hz, H-5 DNTHCz), 7.38 (1H, d, = 8.1 Hz, H-6 DNPh), 7.36–7.24 (4H, m, Ph), 7.19 (1H, d, = 2.6 Hz, H-3 DNPh), 4.81 (1H, m, ), 3.49 (1H, dd, = 18, 9.6 Hz, ), 3.25 (1H, dd, = 18, 9.8 Hz, ), 3.08 (3H, s, OCH₃), 1.75–1.64 (m, 7H, Cyclo). MS (EI): = 601.156 [M]⁺.

8-(5-(4-Chlorophenyl)-4,5-dihydro-1-(2,4-dinitrophenyl)-1H-pyrazol-3-yl)-6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazole (6i). FTIR (KBr) cm⁻¹: 1569 (C=C), 1639 (C=N), 1044 (C-N), 2989 (C-H), 735 (C-Cl), 1450 (C-NO₂). ¹H NMR (-DMSO) δ: 10.54 (1H, s, H-9), 8.32 (1H, d, = 2.1 Hz, H-7 DNTHCz), 7.68 (1H, dd, = 8.4, 2.6 Hz, H-5 DNPh), 7.57 (1H, d, = 2.1 Hz, H-5 DNTHCz), 7.49 (1H, d, = 8.4 Hz, H-6 DNPh), 7.37–7.26 (4H, m, Ph), 7.21 (1H, d, = 2.6 Hz, H-3 DNPh), 4.82 (1H, m, ), 3.52 (1H, dd, = 18, 9.6 Hz, ), 3.29 (1H, dd, = 18, 9.6 Hz, ), 1.76–1.65 (m, 7H, Cyclo). MS (EI): = 605.106 [M]⁺.

8-(5-(Furan-2-yl)-4,5-dihydro-1-(2,4-dinitrophenyl)-1H-pyrazol-3-yl)-6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazole (6j). FTIR (KBr) cm⁻¹: 1578 (C=C), 1647 (C=N), 1045 (C-N), 2996 (C-H), 1159 (C-O-C), 1438 (C-NO₂). ¹H NMR (-DMSO) δ: 10.54 (1H, s, H-9), 8.32 (1H, d, = 2.1 Hz, H-7 DNTHCz), 7.67 (1H, d, = 8.1 Hz, H-5 DNPh), 7.58 (1H, d, = 2.1 Hz, H-5 DNTHCz), 7.49 (1H, dd, = 8.1, 2.6 Hz, H-6 DNPh), 7.38–7.31 (3H, m, Ph), 7.23 (1H, d, = 2.6 Hz, H-3 DNPh), 4.87 (1H, m, ), 3.54 (1H, dd, = 18, 9.7 Hz, ), 3.27 (1H, dd, = 18, 9.7 Hz, ), 1.78–1.66 (m, 7H, Cyclo). MS (EI): = 561.124 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazol-8-yl)-5-phenylpyrazole-1-carbothioamide (6k). FTIR (KBr) cm⁻¹: 1576 (C=C), 1639 (C=N), 1045 (C-N), 2988 (C-H), 3610 (C-NH₂), 1450 (C-NO₂) 1202 (C=S). ¹H NMR (-DMSO) δ: 10.52 (1H, s, H-9), 8.26 (1H, d, = 2.7 Hz, H-7 DNTHCz), 7.57–7.48 (5H, m, Ph), 7.41 (1H, d, = 2.7 Hz, H-5 DNTHCz), 4.86 (1H, m, ), 3.49 (1H, dd, = 18, 9.8 Hz, ), 3.31 (1H, dd, = 18, 9.8 Hz, ), 1.78–1.67 (m, 7H, Cyclo). MS (EI): = 464.127 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazol-8-yl)-5-(2-hydroxyphenyl)pyrazole-1-carbothioamide (6l). FTIR (KBr) cm⁻¹: 1569 (C=C), 1639 (C=N), 1044 (C-N), 2994 (C-H), 3300 (C-OH), 3590 (C-NH₂), 1445 (C-NO₂). ¹H NMR (-DMSO) δ: 10.48 (1H, s, H-9), 8.28 (1H, d, = 2.7 Hz, H-7 DNTHCz), 7.65–7.51 (4H, m, Ph), 7.39 (1H, d, = 2.7 Hz, H-5 DNTHCz), 4.92 (1H, m, ), 3.52 (1H, dd, = 18, 9.6 Hz, ), 3.27 (1H, dd, = 18, 9.6 Hz, ), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 480.122 [M]⁺.

4,5-Dihydro-3-(6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazol-8-yl)-5-(4-methoxyphenyl)pyrazole-1-carbothioamide (6m). FTIR (KBr) cm⁻¹: 1578 (C=C), 1637 (C=N), 1043 (C-N), 2998 (C-H), 1058 (C-OCH₃), 3600 (C-NH₂), 1436 (C-NO₂), 1204 (C=S). ¹H NMR (-DMSO) δ: 10.51 (1H, s, H-9), 8.32 (1H, d, = 2.4 Hz, H-7 DNTHCz), 7.69–7.53 (5H, m, Ph), 7.39 (1H, d, = 2.4 Hz, H-5 DNTHCz), 4.95 (1H, m, ), 3.54 (1H, dd, = 18, 9.8 Hz, ), 3.29 (1H, dd, = 18, 9.8 Hz, ), 3.11 (3H, s, OCH₃), 1.76–1.64 (m, 7H, Cyclo). MS (EI): = 491.137 [M]⁺.

5-(4-Chlorophenyl)-4,5-dihydro-3-(6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazol-8-yl)pyrazole-1-carbothioamide (6n). FTIR (KBr) cm⁻¹: 1576 (C=C), 1648 (C=N), 1045 (C-N), 2992 (C-H), 760 (C-Cl), 3550 (C-NH₂), 1447 (C-NO₂), 1206 (C=S). ¹H NMR (-DMSO): δ: 10.54 (1H, s, H-9), 8.37 (1H, d, = 2.6 Hz, H-7 DNTHCz), 7.62–7.54 (4H, m, Ph), 7.43 (1H, d, = 2.6 Hz, H-5 DNTHCz), 4.93 (1H, m, ), 3.55 (1H, dd, = 18, 9.6 Hz, ), 3.31 (1H, dd, = 18, 9.6 Hz, ), 1.78–1.66 (m, 7H, Cyclo). MS (EI): = 498.088 [M]⁺.

5-(Furan-2-yl)-4,5-dihydro-3-(6,7,8,9-tetrahydro-1,3-dinitro-5H-carbazol-8-yl)pyrazole-1-carbothioamide (6o). FTIR (KBr) cm⁻¹: 1576 (C=C), 1639 (C=N), 1042 (C-N), 2994 (C-H), 1160 (C-O-C), 3580 (C-NH₂), 1449 (C-NO₂), 1202 (C=S). ¹H NMR (-DMSO) δ: 10.57 (1H, s, H-9), 8.36 (1H, d, = 2.4 Hz, H-7 DNTHCz), 7.74–7.57 (3H, m, Ph), 7.41 (1H, d, = 2.4 Hz, H-5 DNTHCz), 4.97 (1H, m, ), 3.57 (1H, dd, = 18, 9.6 Hz, ), 3.32 (1H, dd, = 18, 9.6 Hz, ), 1.80–1.67 (m, 7H, Cyclo). MS (EI): = 454.106 [M]⁺.

3. Results and Discussion

Tetrahydrocarbazole linked 1,2-diazole have become increasingly useful in many fields; prior to the synthesis of title compounds, ketone 1(a–c) was prepared by reported method [16]. Initially, this reaction was carried out in two steps, that is, formation of α,β-unsaturated ketone by the action of ketone 1(a–c) and aromatic aldehydes 2(a–e) in the presence of catalyst. In the later step, addition of hydrazine resulted in the diazole formation and the yield was considerably decreased. In search of better results in terms of yield, reaction time, and easy workup, MCR approach (Scheme 1) had been employed for the synthesis of tetrahydrocarbazole based 1,2-diazoles 4–6(a–o) where 1(a–c), 2(a–e), and 3(a–c) in alkaline medium using 20 mol% sodium methoxide in methanol were stirred together (Table 1).

Scheme 1: Preparation of tetrahydrocarbazoles linked 1,2-diazoles.

The color of reaction mixture gradually amplified upon addition of base which indicated the formation of enolate ion. Slow addition of aldehyde with continuous stirring led in situ to α,β-unsaturated ketone generation indicated by TLC and FTIR which was consumed by hydrazine to furnish titled diazoles in excellent yield. The product was achieved by pouring reaction mixture on crushed ice.

Resultant precipitates were filtered, vacuum dried, and subjected to column chromatography using dichloromethane-methanol as solvent system. Mechanistically, attack of hydrazine took place via Michael type-addition on α,β-unsaturated ketone followed by removal of water which furnishes pyrazoline moiety. Initially, the reaction was carried out in acetic acid : water system but it remained incomplete even after longer time of more than 24 hours. This is why basic conditions were opted for conventional method. Reaction conditions were optimized for conventional heating method using model reaction. 1c, 2a, and 3a were reacted in the presence of different amounts of sodium methoxide as catalyst. Various concentrations were explored where 20 mol% was found to be ideal. Sodium methoxide was most effective in abstracting the proton from sterically hindered ketone (1c) relative to typical sodium hydroxide or potassium hydroxide catalysts. Its small amount was sufficient to provide product in 2.5 hours in terms of yield; increase in catalyst amount decreased the product yield (Table 3).

Table 3: Optimization of reaction conditions.

Entry
Conventional heating
Microwave irradiation

Catalyst (mol%)
Time (hr)
Yield (%)
Catalyst ratio
Time (min)
Yield (%)

(1)
10
5
48
2 : 1
15
32

(2)
20
2.5
75
1 : 1
4
88

(3)
30
4
43
1 : 1.5
6
46

(4)
40
3.5
30
1 : 2
12
38

Sodium methoxide; acetic-acid-water.

To improve and make this approach more benign, clean, and high-yielding, we have attempted to prepare diazoles under microwave radiations. Therefore, to attain benchmark reaction conditions in microwave, ketone (1c), benzaldehyde (2a), and hydrazine hydrate (3a) in 1 : 1 : 1.2 equivalents were exposed to microwave radiations at 300 W. It has been observed that microwave-assisted Aza-Michael reaction proceeds more speedily in acetic acid-water catalytic system than in water alone. This led to exploring various combinations of catalytic system [17].

The aqueous-Brønsted acid system (1 : 1) was used as green solvent and catalyst that demonstrated excellent results while reaction progress was monitored by TLC (Table 3). We were contented on the observation that the reaction proceeded smoothly and almost all the reactants were consumed within 4 minutes to afford the desired product (6a) in satisfactory yield (Table 3, Entry 2). Reaction was also performed on less power levels (200–250 W) but all results led to longer time with incomplete reactants consumption. To inspect the scope and efficacy of the current procedure, reactions between different substrates (1a–c), various aromatic aldehydes with electron donating/withdrawing groups (2a–e), and different hydrazines (3a–c) were carried out and results are summarized in Table 3. From these results, it has been observed that all the reactions proceeded smoothly in very short reaction time to afford the corresponding tetrahydrocarbazole linked 1,2-diazoles in good to excellent (Table 2). Diazoles bearing electron donating groups (-OH, -OCH₃, -furfural) on aromatic ring of carbinol carbon demonstrated remarkable yield. It might be helpful to envision that these groups forcing the electrons towards electrophilic aldehyde group make it tend to be less contented and more reactive. Reaction time reduced significantly from hours to few minutes by applying microwave radiations.

The structure confirmation was achieved with the help of FTIR, ¹H NMR, and mass spectroscopic analysis of the compounds. The protons associated with tetrahydrocarbazole (THCz), 6-nitro tetrahydrocarbazole (NO₂ THCz) and 6,8-dinitrotetrahydrocarbazole (DNTHCz), and aromatic moieties were matched with that of reported in literature [13, 15, 16]. In ¹H NMR, a multiplet at δ 4.85–4.80, 5.38–5.18, and 5.19–4.91 was assigned to enantiotopic proton in 4a–o, 5a–o, and 6a–o, respectively. A doublet resonated at δ 3.68–3.56, 3.58–3.34, and 3.57–3.47 attributed to diastereotopic proton while another doublet at δ 3.38–3.48, 3.31–3.14, 3.32–3.23 corresponds to , in 4a–o, 5a–o, and 6a–o, subsequently confirming 1,2-diazole ring. The singlet responsible for N-H pyrazoline ring was observed at δ 6.27–6.21, 6.37–6.32, and 6.24–6.20 in 4a–e, 5a–e, and 6a–e [18]. Further confirmation of heterocyclic ring formation was endorsed by absorption bands in ranges from 3078 to 3045 cm⁻¹ in FTIR spectrum.

4. Conclusion

In the present study, we have successfully established a rapid, efficient, one-pot, and highly selective synthesis of a new series of tetrahydrocarbazole linked 1,2-diazoles by employing Fischer indole, aldol condensation, and Michael type cycloaddition reactions. Both alkaline and acidic conditions were found suitable to afford desired molecules. Key advantages of described procedure are operational simplicity, shorter reaction time, convenient workup, and high yields. We are optimistic to construct novel structural leads in the domains of heterocyclic chemistry. This new synthetic series is remarkable as both key units THCz and 1,2-diazole has renowned biological profile. We believe that our procedure is user-friendly and economically cheap due to inexpensive catalyst and simple synthetic protocols.

Conflicts of Interest

The authors declare no conflicts of interest regarding this work.

Acknowledgments

The authors are grateful to Higher Education Commission, Pakistan, for providing the generous grant to carry out this project and analysis.

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