Preparation of novel symmetrical bistetrazole-carbazole derivatives through a one-pot Ugi-azide reaction

Article abstract of DOI:10.1002/jhet.4206

A series of new symmetrical tetrazole-based carbazole derivatives starting from the initially generated 3,6-diformyl-N-alkylcarbazoles were successfully synthesized through a one-pot Ugi-azide reaction in moderate to high yields. Simplicity, easily accessible chemicals, mild reaction conditions, and fast separation of the products with the formation of bistetrazole-based carbazole derivatives in one step are some advantages of this method. The structure of the products was characterized and confirmed by using spectroscopic techniques such as ¹H NMR, ¹³C NMR, FT-IR, and MS spectroscopy.

Full text of DOI:10.1002/jhet.4206

Preparation of Novel Symmetrical Bistetrazole-Carbazole
Derivatives through a One-Pot Ugi-Azide Reaction
*
Shahnaz Rahimi , Mehdi Ghandi
School of Chemistry, College of Science, University of Tehran, 16th Azar St.,
Enghelab Sq., 141556455 Tehran, Iran
Email: sh.rh1989@gmail.com
Abstract
A series of new symmetrical tetrazole-based carbazole derivatives starting from the initially generated 3,6-
diformyl-N-alkylcarbazoles were successfully synthesized through a one-pot Ugi-azide reaction in moderate to
high yields. Simplicity, easily accessible chemicals, mild reaction conditions, and fast separation of the products
with the formation of bistetrazole-based carbazole derivatives in one step are some advantages of this method.
1
The structure of the products was characterized and confirmed by using spectroscopic techniques such as H
13
NMR, C NMR, FT-IR, and MS spectroscopy.
Keywords: Carbazole; four-component reaction; one pot reaction; tetrazole; Ugi-azide reaction
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not been through the copyediting, typesetting, pagination and proofreading process
which may lead to differences between this version and the Version of Record. Please
cite this article as doi: 10.1002/jhet.4206
1
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TOC GRAPHIC
Introduction
The so-called bis-heterocycles are scaffolds produced through two fused, linked bound, merged
and/or spaced heterocyclic groups. They have been the focus of various studies in recent years due to
the preparation of novel hybrid complex molecules, which can improve their biological activities
compared to individual analogues. These heterocycles have been reported in different fields such as
pharmaceutical, agrochemical, optics, electrical materials, polymer sciences, and other emerging
[1-4]
areas.
2
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Carbazole ring (benzo[b]indole), an important tricyclic heterocyclic compound, which is widespread
in nature, has attracted a growing interest in recent years due to the unique biological activities
including antitumor, antimicrobial, antihistaminic, antifungal, antioxidant, hepatoprotective,
[5-10]
antidiabetic, analgesic, anti-HIV, anti-protozoan, and sedative activities.
Furthermore, carbazole
[11]
[12]
scaffold is found in several natural and synthetic drugs like carazostatin,
carprofen,
and
[13]
carvedilol (Figure 1). On the other hand, the azole groups like imidazole, triazole and tetrazole are
important pharmacophores, existing extensively in the molecular structure of many types of
pharmaceutical agents with a variety of pharmacological activities. In this regard, a series of carbazole
derivatives linked with the imidazole and triazole groups have been developed and their biological
[14-16]
activities have been tested.
For instance, a series of some carbazole linked triazoles could act as
[17]
[18]
[19]
acetylcholinesterase (AChE),
non-sugar α-glucosidase,
and β-glucuronidase inhibitors.
Therefore, the carbazole structures remain as the interesting building blocks in the search of novel
biological compounds.
Figure 1. Biologically active compounds containing a carbazole structure.
1,5-Disubstituted-1H-tetrazoles (1,5-DS-1H-T), the most common structure of tetrazoles, are the cis-
amide peptide-bond isosteres, which is found in many commercial drugs like cefamandole (an
antibiotic), cilostazol (anti-inflammatory), moxalactam (anti-microbial) and nojiritetrazole
[20-24]
(
antidiabetic) (Figure 2).
The main approaches for the preparation of biological agents containing
3
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the 1,5-DS-1H-T scaffold are the Ugi-azide and the intermolecular cycloaddition [3 + 2] click
[25-27]
reactions.
Multi-component reactions (MCRs) are useful and important approaches in which minimum three
different substances react together in a one-pot manner to achieve the target scaffolds. These reactions
have widely been applied as effective methods for the synthesis of pharmacologically attractive
[28-30]
scaffolds.
Undoubtedly, one of the most powerful and well-known MCRs is the Ugi four-
component reaction (U-4CR), in which an aldehyde, an amine, an isocyanide and a carboxylic acid
[31,32]
react in a one-pot manner to gain the substituted α‐amino acylamides.
The Ugi-azide reaction is a
development on the U-4CR, in which the carboxylic acid substance is replaced by an azide source
[33-
such as trimethylsilyl azide (TMSN ) or hydrazoic acid (HN ) for accessing novel 1,5-DS-1H-T’s.
3
3
3
6]
[37,38]
Particularly significant is that with some exceptions,
the preparation of bis-tetrazoles via the
Ugi-azide reaction has rarely been reported previously.
Figure 2. Drugs and biologically active compounds containing a 1,5-DS-1H-T ring.
To the best of our knowledge, there is no report about the preparation of bis-heterocycles containing
a carbazole core linked with 1,5-DS-1H-T’s through MCRs. Therefore, based on the documented
pharmacological potential of these two building blocks, and our interest in the synthesis of tetrazole
[39-42]
derivatives using the isocyanide-based multicomponent reactions (IMCRs)
, herein, we describe
the synthesis of novel symmetrical analogues of 1,5-DS-1H-T containing carbazole derivatives via the
4
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Ugi-azide reaction of 3,6-diformyl-9-alkylcarbazoles, aromatic amines, isocyanides and trimethylsilyl
azide (TMSN ) in methanol.
3
Results and discussion
Initially, 3,6-diformyl-9-alkylcarbazoles 3a-b were synthesized via the previously reported method
[43]
(
Scheme 1).
In the next step, the Ugi-azide reaction of 3,6-diformyl-9-alkylcarbazoles 3a-b
underwent reaction with various primary anilines 4a–e, isocyanides 5a–c and TMSN in MeOH at
3
room temperature within 24 h to afford bis-tetrazole based carbazoles 6a-l in moderate to high yields
(
Scheme 2). To gain the optimum reaction conditions, besides MeOH, other solvents such as EtOH,
CH Cl , THF and H O were examined, which did not afford any better result in comparison with
2
2
2
MeOH (Table 1). It was also observed that the use of TMSN in the reaction has given the higher yield
3
as compared to NaN . Therefore, the best reaction conditions for the synthesis of 1,5-DS-1H-T
3
containing carbazole moiety were obtained in MeOH as solvent and TMSN as azide source after 24 h.
3
Scheme 1. Preparation of 3,6-diformyl-9-alkylcarbazoles 3a-b.
5
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Scheme 2. Preparation of novel bis-tetrazole based carbazoles 6a-l.
The scope and the efficiency of this approach were examined using aniline derivatives containing
different substituents and various isocyanides under the same reaction condition (Table 2).
Table 1. Optimum reaction conditions for compound 6b.
Entry
Solvent
Azide
Time
h)
Temperature
(°C)
Yield
(%)
(
1
2
3
4
5
6
7
CH Cl
TMSN3
TMSN3
TMSN3
TMSN3
TMSN3
NaN3
24
24
24
12
24
24
24
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
24
57
32
55
76
43
18
2
2
EtOH
H O
2
MeOH
MeOH
MeOH
THF
TMSN3
1
The chemical structure of all products 6a–l was characterized and confirmed by using H NMR and
1
3
C NMR (Supplementary, Figures S1–S24), FT-IR, MS spectroscopy, and elemental analysis. For
1
instance, part of the H NMR spectrum of 6a showed the characteristic peaks at δ 1.40, 1.73, 4.31,
4
.92, and 6.33 due to CH Me, 2CMe , CH Me, 2CHNH and 2CHNH, respectively (Figure S1). In
2 3 2
13
addition, the C NMR spectrum of 6a revealed 16 distinct peaks due to 5 aliphatic and 11 aromatic
carbons in agreement with the suggested structure (Figure S2).
6
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[a]
Table 2. Synthesis of novel bis-tetrazole based carbazole derivatives 6a–l .
1
2
Entry
R
R
Amine
Product
Yield (%)
1
2
3
4
5
6
7
8
9
Et
t-Bu
Ph-NH2
6a
6b
6c
6d
6e
6f
64
76
52
59
46
71
65
76
79
88
74
92
Et
t-BuCH CMe2
Ph-NH2
2
Me
Et
t-BuCH CMe2
Ph-NH2
2
t-Bu
t-Bu
4-Me-Ph-NH2
3,4-diMe-Ph-NH2
3,4-diMe-Ph-NH2
4-Cl-Ph-NH2
4-Cl-Ph-NH2
4-Cl-Ph-NH2
4-Cl-Ph-NH2
4-Cl-Ph-NH2
2-Br-Ph-NH2
Me
Et
t-BuCH CMe2
2
Me
Me
Et
t-Bu
6g
6h
6i
t-BuCH CMe2
2
t-Bu
1
1
1
0
1
2
Et
t-BuCH CMe2
6j
2
Et
Cy
6k
6l
Et
t-BuCH CMe2
2
[
a] Reaction conditions: 3,6-diformyl-9-alkylcarbazoles 3a-b (0.5 mmol), aromatic amines (1.0 mmol),
isocyanides (1.0 mmol), TMSN (1.0 mmol), and MeOH (5 mL) at r.t. for 24 h.
3
The proposed mechanism for the preparation of symmetrical bistetrazole-carbazole derivatives 6a-l
is illustrated in Scheme 3. The initially formed imines I from condensation between 3,6-diformyl-N-
1
alkylcarbazoles 3a-b with aromatic amines 4a-e are converted into the corresponding iminium ions I2
by the in situ generated hydrazoic acid (Scheme 3). Subsequently, I undergoes nucleophilic reaction
2
with isocyanides 5a-c to give the nitrilium ions I , which are attacked by the azide anion to provide
3
azidoazomethine intermediates I . Finally, 1,3 dipolar electrocyclization affords the bis-tetrazole based
4
carbazoles 6a-l.
7
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Scheme 3. Suggested mechanism for the synthesis of 6a–l.
Conclusion
In summary, we designed a facile and practical procedure for the preparation of new symmetrical
bis-tetrazole based carbazoles derivatives through an Ugi-azide process in moderate to excellent
yields. This protocol is highly beneficial in terms of structural complexity, atom economy, and the use
of the accessible starting materials. The synthesized compounds can develop the scaffolds that are
available via the Ugi-azide four-component reactions, and a lot of them might exhibit promising
biological properties.
Experimental Section
General information. All commercially accessible starting materials and reagents were obtained
from Merck Chemical Company and used without further purification. FT-IR spectra were recorded
-1
1
13
by using a Shimadzu 4300 spectrophotometer, in cm . H and C NMR spectra were recorded at
room temperature on a Bruker 500 MHz spectrometer by using CDCl and DMSO-d as the solvent.
3
6
Chemical shifts are reported in parts per million (δ/ppm). Mass spectra of the synthesized products
were performed with an HP (Agilent Technologies, Santa Clara, CA, USA) 5937 Mass Selective
8
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Detector. Elemental analyses were carried out via a CHN-Rapid Heraeus elemental analyzer. Melting
points were performed with an Electrothermal model 9100 apparatus and are uncorrected.
General procedure for the synthesis of compounds 6a-l
To a solution of 3,6-diformyl-N-alkylcarbazole (0.5 mmol) in methanol (5 mL) was added primary
aniline derivatives (1.0 mmol), and the mixture was stirred for 15 min. After that, TMSN (0.115 g,
3
1.0 mmol) and isocyanide (1.0 mmol) were added and the reaction mixture stirred for 24 h at room
temperature. After completion as indicated by TLC, the solid products were filtered off and washed
with EtOH and recrystallized from EtOAC/n-Hex to afford the desired products 6a–l.
N,N'-((9-ethyl-9H-carbazole-3,6-diyl)bis((1-(tert-butyl)-1H-tetrazol-5-yl)methylene))dianiline (6a).
Yellow solid (64% yield); mp 180-182 °C; IR (KBr) νmax: 752, 1101, 1237, 1491, 1600, 2975, 3335
-
1 1
cm ; H NMR (500 MHz, CDCl ) δ 1.40 (3H, t, J = 5.5 Hz, CH Me), 1.73 (18H, s, CMe ), 4.31 (2H,
3
2
3
q, J = 5.5 Hz, CH Me), 4.92 (2H, brs, CHNH), 6.33 (2H, brs, CHNH), 6.72-6.78 (6H, m, Ar), 7.16-
2
1
3
7
.19 (4H, m, Ar), 7.38 (2H, d, J = 7.3 Hz, Ar), 7.49 (2H, d, J = 7.1 Hz, Ar), 8.10 (2H, s, Ar) ppm; C
NMR (125 MHz, CDCl ) δ 14.30 (CH Me), 30.17 (CMe ), 38.62 (CH Me), 54.92 (CHNH), 61.28
3
2
3
2
(
CMe ), 109.33, 114.34, 119.13, 120.24, 122.94, 125.82, 128.91, 129.41, 140.31, 145.92, 155.72
3
(
C―Ar) ppm; m/z (EI, 70 eV) 577 (2), 551 (2), 448 (9), 401 (5), 356 (48), 323 (20), 272 (52), 244
22), 93 (88), 57 (100%); Anal. Calcd for C H N : C, 69.81, H, 6.63, N, 23.57. Found: C, 69.83, H,
(
3
8
43 11
6.59, N, 23.58%.
N,N'-((9-ethyl-9H-carbazole-3,6-diyl)bis((1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-5-
yl)methylene))dianiline (6b). Light yellow solid (76% yield); mp 195-198 °C; IR (KBr) νmax: 751,
-1 1
1
100, 1240, 1498, 1601, 2954, 3325 cm ; H NMR (500 MHz, CDCl ) δ 0.62 (18H, s, CMe ), 1.36
3
3
(
3H, t, J = 5.4 Hz, CH Me), 1.81 and 1.86 (12H, 4s, CMe ), 1.98 (4H, ABq, J = 15 Hz, CCH C), 4.30
2 2 2
(
2H, q, J = 5.3 Hz, CH Me), 4.96 (2H, brs, CHNH), 6.35 (2H, s, CHNH), 6.74-6.77 (6H, m, Ar), 7.18
2
1
3
(
4H, m, Ar), 7.37 (2H, d, J = 7.3 Hz, Ar), 7.60 (2H, d, J = 7.1 Hz, Ar), 8.14 (2H, s, Ar) ppm; C NMR
(
125 MHz, CDCl ) δ 13.74 (CH Me), 30.36 (CMe ), 30.48 (CMe ), 31.56 (CMe ), 37.76 (CH Me),
3
2
3
3
2
2
5
3.15 (CHNH), 55.40 (CCH C), 65.39 (CMe ), 110.04, 114.72, 119.21, 120.37, 122.85, 126.04,
2 2
9
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128.89, 129.39, 140.24, 145.88, 156.01 (C―Ar) ppm; m/z (EI, 70 eV) 523 (1), 412 (1), 368 (3), 272
(
3), 243 (20), 211 (6), 112 (53), 93 (52), 41 (100%); Anal. Calcd for C H N : C, 72.12, H, 7.76, N,
4
6
59 11
20.11. Found: C, 72.08, H, 7.74, N, 20.17%.
N,N'-((9-methyl-9H-carbazole-3,6-diyl)bis((1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-5-
yl)methylene))dianiline (6c). Orange solid (52% yield); mp 199-201 °C; IR (KBr) νmax: 804, 1114,
-
1 1
1
4
248, 1488, 1591, 2951 cm ; H NMR (500 MHz, CDCl ) δ 0.65 (18H, s, CMe ), 1.81 and 1.86 (12H,
3 3
s, CMe ), 2.01 (4H, ABq, J = 12.5 Hz, CCH C), 3.80 (3H, s, Me), 5.04 (2H, brs, CHNH), 6.39 (2H,
2
2
brs, CHNH), 6.78 (6H, m, Ar), 7.18 (4H, m, Ar), 7.37 (2H, d, J = 8.3 Hz, Ar), 7.61 (2H, d, J = 8.4 Hz,
1
3
Ar), 8.14 (2H, s, Ar) ppm; C NMR (125 MHz, CDCl ) δ 29.31 (CMe ), 29.47 (CMe ), 31.54 (CMe ),
3
3
3
2
4
1
1.34 (Me), 53.73 (CHNH), 55.88 (CCH C), 65.31 (CMe ), 109.33, 114.34, 119.13, 120.24, 122.94,
2 2
25.82, 128.91, 129.41, 140.31, 145.92, 155.72 (C―Ar) ppm; m/z (EI, 70 eV) 524 (2), 448 (4), 340
(
10), 272 (18), 244 (36), 92 (75), 57 (100%); Anal. Calcd for C H N : C, 71.78, H, 7.64, N, 20.49.
45 57 11
Found: C, 71.42, H, 7.74, N, 20.84%.
N,N'-((9-ethyl-9H-carbazole-3,6-diyl)bis((1-(tert-butyl)-1H-tetrazol-5-yl)methylene))bis(4-
methylaniline) (6d). White solid (59% yield); mp 177-180 °C; IR (KBr) νmax: 805, 1236, 1481, 1516,
-1
1
1
612, 2985, 3367 cm ; H NMR (500 MHz, CDCl ) δ 1.41-1.48 (3H, m, CH Me), 1.73 (18H, s,
3
2
CMe ), 2.23 (6H, s, Me), 4.10 (2H, q, J = 5 Hz, CH Me), 5.04 (2H, brs, CHNH), 6.31 (2H, s, CHNH),
3
2
6
7
3
1
.68 (4H, d, J = 8.1 Hz, Ar), 6.98 (4H, d, J = 8.2 Hz, Ar), 7.48 (2H, d, J = 7.1 Hz, Ar), 7.54 (2H, d, J =
13
.2 Hz, Ar), 8.12 (2H, brs, Ar) ppm; C NMR (125 MHz, CDCl ) δ 14.30 (CH Me), 20.03 (Me),
3
2
0.10 (CMe ), 37.85 (CH Me), 55.11 (CHNH), 61.90 (CMe ), 109.40, 115.54, 120.34, 122.89, 123.86,
3
2
3
26.07, 128.51, 129.25, 143.98, 149.43, 161.28 (C―Ar) ppm; m/z (EI, 70 eV) 551 (5), 523 (5), 466
6), 360 (24), 276 (36), (20), 248 (18), 191 (6), 91 (21), 57 (100%); Anal. Calcd for C H N : C,
(
4
0
47 11
70.46, H, 6.95, N, 22.60. Found: C, 70.51, H, 6.91, N, 22.58%.
N,N'-((9-methyl-9H-carbazole-3,6-diyl)bis((1-(tert-butyl)-1H-tetrazol-5-yl)methylene))bis(3,4-
dimethylaniline) (6e). Orange solid (46% yield); mp 185-187 °C; IR (KBr) νmax: 807, 1113, 1248,
-1 1
1
388, 1523, 2958, 3052 cm ; H NMR (500 MHz, CDCl ) δ 1.53 (18H, s, CMe ), 2.17 (6H, s, Me),
3
3
1
0
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2.23 (6H, s, Me), 3.72 (3H, s, Me), 4.92 (2H, brs, CHNH), 6.33 (2H, s, CHNH), 6.55-6.60 (4H, m,
Ar), 6.92 (2H, d, J = 7.5 Hz, Ar), 7.37 (2H, d, J = 7.2 Hz, Ar), 7.58 (2H, d, J = 7.5 Hz, Ar), 8.02 (2H,
1
3
s, Ar) ppm; C NMR (125 MHz, CDCl ) δ 19.14 (Me), 20.03 (Me), 30.17 (CMe ), 45.92 (Me), 54.92
3
3
(
CHNH), 61.28 (CMe ), 109.33, 114.34, 119.13, 120.24, 122.94, 125.82, 128.91, 129.41, 131.40,
3
136.40, 140.31, 145.92, 155.72 (C―Ar) ppm; m/z (EI, 70 eV) 582 (2), 462 (6), 412 (4), 350 (28), 272
(
21), 244 (62), 92 (44), 41 (100%); Anal. Calcd for C H N : C, 70.76, H, 7.10, N, 22.14. Found: C,
4
1
49 11
71.28, H, 6.62, N, 22.10%.
N,N'-((9-ethyl-9H-carbazole-3,6-diyl)bis((1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-5-
yl)methylene))bis(3,4-dimethylaniline) (6f). White solid (71% yield); mp 190-193 °C; IR (KBr) νmax
:
-
1 1
8
1
2
08, 1013, 1238, 1488, 1613, 2948, 3362 cm ; H NMR (500 MHz, CDCl ) δ 0.63 (18H, s, CMe ),
3 3
.36 (3H, t, J = 5.7 Hz, CH Me), 1.81 and 1.85 (12H, 4s, CMe ), 1.98 (4H, ABq, J = 15 Hz, CCH C),
2
2
2
.12 (6H, s, Me), 2.17 (6H, s, Me), 4.30 (2H, q, J = 6 Hz, CH Me), 4.80 (2H, brs, CHNH), 6.33 (2H, s,
2
CHNH), 6.55-6.60 (4H, m, Ar), 6.93 (2H, d, J = 7.6 Hz, Ar), 7.36 (2H, d, J = 7.1 Hz, Ar), 7.57 (2H, d,
13
J = 7.6 Hz, Ar), 8.12 (2H, s, Ar) ppm; C NMR (125 MHz, CDCl ) δ 14.19 (CH Me), 19.14 (Me),
3
2
2
0.03 (Me), 30.37 (CMe ), 30.51 (CMe ), 32.01 (CMe ), 37.75 (CH Me), 53.73 (CHNH), 55.88
3 3 2 2
(
CCH C), 65.31 (CMe ), 109.26, 112.23, 116.94, 120.40, 122.91, 126.01, 127.87, 129.65, 131.40,
2 2
136.40, 140.20, 143.98, 155.57 (C―Ar) ppm; m/z (EI, 70 eV) 577 (1), 509 (5), 412 (3), 350 (26), 272
(
9), 244 (75), 228 (77), 106 (85), 41 (100%); Anal. Calcd for C H N : C, 73.05, H, 8.21, N, 18.74.
50 67 11
Found: C, 72.98, H, 8.26, N, 18.76%.
N,N'-((9-methyl-9H-carbazole-3,6-diyl)bis((1-(tert-butyl)-1H-tetrazol-5-yl)methylene))bis(4-
chloroaniline) (6g). Yellow solid (65% yield); mp 198-201 °C; IR (KBr) νmax: 803, 1100, 1248, 1492,
-1 1
1
597, 2918, 3345 cm ; H NMR (500 MHz, CDCl ) δ 1.52 (18H, s, CMe ), 3.65 (3H, Me), 4.92 (2H,
3
3
brs, CHNH), 6.27 (2H, brs, CHNH), 6.64 (4H, d, J = 8 Hz, Ar), 7.09 (4H, d, J = 8 Hz, Ar), 7.38 (2H,
1
3
d, J = 7.1 Hz, Ar), 7.48 (2H, d, J = 7.2 Hz, Ar), 8.14 (2H, s, Ar) ppm; C NMR (125 MHz, CDCl ) δ
3
3
0.17 (CMe ), 41.34 (Me), 55.11 (CHNH), 61.90 (CMe ), 115.92, 120.26, 120.73, 122.70, 126.13,
3
3
128.01, 128.60, 129.27, 143.98, 149.43, 161.28 (C―Ar) ppm; m/z (EI, 70 eV) 577 (2), 468 (10), 412
1
1
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(
16), 356 (58), 341 (612), 272 (72), 244 (34), 92 (44), 57 (100%); Anal. Calcd for C H Cl N : C,
37 39 2 11
62.71, H, 5.55, N, 21.74. Found: C, 62.77, H, 5.52, N, 21.70%.
N,N'-((9-methyl-9H-carbazole-3,6-diyl)bis((1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-5-
yl)methylene))bis(4-chloroaniline) (6h). Yellow solid (76% yield); mp 240-242 °C; IR (KBr) νmax
:
-
1 1
8
1
03, 1100, 1248, 1492, 1597, 2918, 3345 cm ; H NMR (500 MHz, CDCl ) δ 0.62 (18H, s, CMe ),
3 3
.80 and 1.84 (12H, 4s, CMe ), 1.98 (4H, ABq, J = 15.5 Hz, CCH C), 3.79 (3H, s, Me), 5.01 (2H, brs,
2
2
CHNH), 6.27 (2H, s, CHNH), 6.70 (2H, d, J = 7.3 Ar), 7.11 (2H, d, J = 7.6 Hz, Ar), 7.36 (2H, d, J =
1
3
7
.9 Hz, Ar), 7.58 (2H, d, J = 7.1 Hz, Ar), 8.12 (2H, s, Ar) ppm; C NMR (125 MHz, CDCl ) δ 29.31
3
(
CMe ), 29.47 (CMe ), 31.54 (CMe ), 41.34 (Me), 53.74 (CHNH), 55.59 (CCH C), 65.45 (CMe ),
3 3 2 2 2
109.40, 115.92, 120.26, 120.73, 122.70, 126.13, 128.01, 128.60, 129.27, 144.44, 155.68 (C―Ar) ppm;
m/z (EI, 70 eV) 524 (4), 422 (15), 398 (25), 343 (17), 286 (26), 258 (93), 230 (80), 127 (27), 57
(
100%); Anal. Calcd for C H Cl N : C, 65.84, H, 6.75, N, 18.77. Found: C, 65.80, H, 6.71, N,
45 55 2 11
18.86%.
N,N'-((9-ethyl-9H-carbazole-3,6-diyl)bis((1-(tert-butyl)-1H-tetrazol-5-yl)methylene))bis(4-
chloroaniline) (6i). White solid (79% yield); mp 200-204 °C; IR (KBr) νmax: 822, 1101, 1238, 1491,
-1 1
1
599, 2981, 3329 cm ; H NMR (500 MHz, CDCl ) δ 1.40 (3H, t, J = 5 Hz, CH Me), 1.71 (18H, s,
3
2
CMe ), 4.31 (2H, q, J = 5 Hz, CH Me), 5.01 (2H, brs, CHNH), 6.27 (2H, brs, CHNH), 6.64 (4H, d, J =
3
2
8
8
5
1
.1 Hz, Ar), 7.09 (4H, d, J = 7.9 Hz, Ar), 7.38 (2H, d, J = 7.1 Hz, Ar), 7.48 (2H, d, J = 7.2 Hz, Ar),
13
.08 (2H, s, Ar) ppm; C NMR (125 MHz, CDCl ) δ 13.85 (CH Me), 30.10 (CMe ), 37.85 (CH Me),
3
2
3
2
5.11 (CHNH), 61.90 (CMe ), 109.40, 115.52, 120.20, 122.94, 123.76, 125.85, 128.55, 129.25,
3
40.37, 144.54, 155.41 (C―Ar) ppm; m/z (EI, 70 eV) 577 (1), 482 (8), 412 (3), 356 (63), 300 (6), 272
(
68), 244 (28), 191 (11), 127 (40), 57 (100%); Anal. Calcd for C H Cl N : C, 63.15, H, 5.72, N,
38 41 2 11
21.32. Found: C, 63.13, H, 5.77, N, 21.26%.
N,N'-((9-ethyl-9H-carbazole-3,6-diyl)bis((1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-5-
yl)methylene))bis(4-chloroaniline) (6j). White solid (88% yield); mp 210-211 °C; IR (KBr) νmax: 823,
-1 1
1
098, 1240, 1489, 1599, 2954, 3421 cm ; H NMR (500 MHz, CDCl ) δ 0.61 (18H, s, CMe ), 1.36
3
3
1
2
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(
(
3H, t, J = 5.2 Hz, CH Me), 1.81 and 1.86 (12H, 4s, CMe ), 1.96 (4H, ABq, J = 15 Hz, CCH C), 4.30
2 2 2
2H, q, J = 5.6 Hz, CH Me), 5.04 (2H, brs, CHNH), 6.27 (2H, s, CHNH), 6.69 (4H, d, J = 8.1 Hz, Ar),
2
7.10 (4H, d, J = 8.3 Hz, Ar), 7.37 (2H, d, J = 7.3 Hz, Ar), 7.58 (2H, d, J = 7.4 Hz, Ar), 8.12 (2H, s, Ar)
1
3
ppm; C NMR (125 MHz, CDCl ) δ 13.74 (CH Me), 30.37 (CMe ), 30.42 (CMe ), 30.49 (CMe ),
3
2
3
3
3
3
1
5
1.52 (CMe ), 37.81 (CH Me), 53.72 (CHNH), 55.53 (CCH C), 65.48 (CMe ), 109.43, 115.83,
2 2 2 2
20.34, 122.89, 123.86, 126.07, 128.51, 129.25, 140.31, 144.47, 155.70 (C―Ar) ppm; m/z (EI, 70 eV)
38 (5), 412 (30), 357 (15), 300 (21), 272 (92), 244 (58), 191 (13), 127 (30), 57 (100%); Anal. Calcd
for C H Cl N : C, 66.17, H, 6.88, N, 18.45. Found: C, 66.19, H, 6.91, N, 18.39%.
4
6
57
2
11
N,N'-((9-ethyl-9H-carbazole-3,6-diyl)bis((1-cyclohexyl-1H-tetrazol-5-yl)methylene))bis(4-
chloroaniline) (6k). White solid (74% yield); mp 254-257 °C; IR (KBr) νmax: 816, 1091, 1238, 1493,
-1
1
1
600, 2936, 3376 cm ; H NMR (500 MHz, DMSO-d ) δ 1.13-1.38 (10H, m, 5CH of cyclohexyl,
6
2
CH Me), 1.53-1.61 (3H, m, CH Me), 1.80-2.10 (10H, m, 5CH of cyclohexyl, CH Me), 4.41 (2H, q, J
2
2
2
2
=
5.7 Hz, CH Me), 4.64-4.69 (2H, m, CH of cyclohexyl), 6.51 (2H, brs, CHNH), 6.84 (4H, d, J = 8
2
13
Hz, Ar), 7.04 (2H, brs, CHNH), 7.12 (4H, d, J = 8 Hz, Ar), 7.64 (4H, s, Ar), 8.15 (2H, s, Ar) ppm; C
NMR (125 MHz, DMSO-d ) δ 14.12 (CH Me), 24.89 (CH ), 25.04 (2CH ), 25.21 (CH ), 32.87 (CH ),
6
2
2
2
2
2
3
7.65 (CH Me), 51.59 (CHNH), 57.30 (CH of cyclohexyl), 110.03, 115.27, 119.68, 120.94, 122.33,
2
126.37, 129.00, 129.24, 140.07, 146.36, 155.79 (C―Ar) ppm; m/z (EI, 70 eV) 577 (1), 551 (1), 412
(
3), 386 (9), 358 (34), 333 (6), 272 (8), 248 (14), 208 (20), 111 (22), 83 (45), 55 (100%); Anal. Calcd
for C H Cl N : C, 65.11, H, 5.85, N, 19.89. Found: C, 65.15, H, 5.88, N, 19.81%.
4
2
45
2
11
N,N'-((9-ethyl-9H-carbazole-3,6-diyl)bis((1-(2,4,4-trimethylpentan-2-yl)-1H-tetrazol-5-
yl)methylene))bis(2-bromoaniline) (6l). Orange solid (92% yield); mp 265-268 °C; IR (KBr) νmax
:
-1 1
7
44, 1080, 1237, 1487, 1592, 2956, 3372 cm ; H NMR (500 MHz, CDCl ) δ 0.65 and 0.67 (18H, 2s,
3
CMe ), 1.35 (3H, m, CH Me), 1.86, 1.87, 1.88 and 1.89 (12H, 4s, CMe ), 1.99 (4H, ABq, J = 15 Hz,
3
2
2
CCH C), 4.25 (2H, m, CH Me), 5.61 (2H, m, CHNH), 6.38 and 6.39 (2H, 2brs, CHNH), 6.62 (2H, m,
2
2
Ar), 6.78 (2H, m, Ar), 7.12 (2H, m, Ar), 7.33 (2H, m, Ar), 7.44 (2H, m, Ar), 7.64 (2H, m, Ar), 8.15
1
3
(
(
2H, m, Ar) ppm; C NMR (125 MHz, CDCl ) δ 13.78 (CH Me), 30.27 (CMe ), 30.31 (CMe ), 30.53
3 2 3 3
CMe ), 30.55 (CMe ), 30.66 (CMe ), 31.56 (CMe ), 31.59 (CMe ), 37.77 (CH Me), 53.79 (2CHNH),
3
3
3
2
2
2
1
3
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5
1
1
1
5
4.76 (2CCH C), 65.57 (2CMe ), 109.49, 111.05, 111.10, 112.98, 113.02, 119.62, 119.66, 120.26,
2 2
22.72 (2C), 125.93, 125.96, 128.24 (2C), 128.42 (2C), 132.90, 132.94, 140.31 (2C), 142.80 (2C),
55.64 (2C) (C―Ar) ppm; m/z (EI, 70 eV) 584 (2), 443 (2), 412 (44), 300 (18), 272 (99), 244 (60),
71 (60), 92 (38), 57 (100%); Anal. Calcd for C H Br N : C, 59.80, H, 6.22, N, 16.68. Found: C,
4
6
57
2
11
9.74, H, 6.25, N, 16.73%.
Supporting Information
1
13
H NMR and C NMR spectra for the synthesized compounds 6a-l are given in the Supporting Information.
Acknowledgements
We gratefully acknowledge the University of Tehran for financial support.
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