Synthesis of carboxamide and sulfonyl carboxamide linked heterocycles under green conditions

Article abstract of DOI:10.24820/ark.5550190.p010.820

Direct coupling of heteroaldehydes with heteroaryl amines / sulfonylamines is performed under green conditions using PEG-400 in the presence of oxidant CCl3CN/H2O2. The presence of electron withdrawing substituents on heteroaldehydes increased the yield. Further heteroaryl amines favor the reaction when compared with heteroaryl sulfonylamines.

Full text of DOI:10.24820/ark.5550190.p010.820

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Organic Chemistry
Arkivoc 2019, part vi, 0-0
Synthesis of carboxamide and sulfonyl carboxamide linked heterocycles
under green conditions
Lakshmi Teja Gaddam, Sreenivasulu Thata, Padmaja Adivireddy, and
Padmavathi Venkatapuram*
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India
Email: vkpuram2001@yahoo.com
Received 11-20-2018
Accepted 07-22-2019
Published on line 08-04-2019
Abstract
Direct coupling of heteroaldehydes with heteroaryl amines / sulfonylamines is performed under green
conditions using PEG-400 in the presence of oxidant CCl3CN/H2O2. The presence of electron withdrawing
substituents on heteroaldehydes increased the yield. Further heteroaryl amines favor the reaction when
compared with heteroaryl sulfonylamines.
Keywords: Heteroaldehydes, heteroaryl amines , sulfonylamines, oxidant, PEG-400, amidation
DOI: https://doi.org/10.24820/ark.5550190.p010.820
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Introduction
Amide moiety represents a privileged structural motif and it plays an important role in the composition of
polymers, proteins, natural products and pharmaceuticals.1,2 Various approaches were explored for efficient
construction of this significant skeleton.3,4 The most common synthetic route relies on the reactions of activated
carboxylic acids and their derivatives with amines.5-7 However, this method has innate drawbacks, for instance, a
large amount of byproducts are generated leading to lower yields. As a result, alternative methods for amide
synthesis have been developed viz., Beckmann rearrangement,8 azide based modified Staudinger-Vilarrasa
reaction,9 amidation of aryl halides,10 oxidative amidation of aldehydes11 or alcohols12 and amidation of alkynyl
bromide with amines.13 Most of these reactions require relatively harsh conditions such as light, expensive
oxidant, strong bases, transition-metal complexes viz., Cu, Zn, Zr, Ru, Pd, Hg,14 high temperature etc. As such
there is a quest for efficient and economically viable methods to construct amide bond. In continuation of our
interest on green-reaction conditions for organic transformations15 we herein report a simple and efficient
protocol for the synthesis of carboxamide and sulfonyl carboxamide linked heterocycles using PEG-400 in the
presence of an oxidant CCl3CN/H2O2 as eco-friendly and recyclable medium.
Figure 1. The most common reactions for amide bond synthesis.
Results and Discussion
For the last couple of years we have been actively engaged on the development of functionalized heterocycles
linked by amide and sulfonamide moieties. In fact, we have reported the reaction between heteroaryl acids and
heteroaryl amines to develop amide linkage using 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethylaminium
tetrafluoroborate (TBTU)/ N,N-diisopropylethylamine (DIPEA)/ N,N-dimethylformamide (DMF),16 N,N'-
dicyclohexylcarbodiimide (DCC)/ 4-dimethylaminopyridine (DMAP)/ Dioxane,17,18 1-[bis(dimethylamino)methylene]-
1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxidehexafluorophosphate (HATU)/ DIPEA/DMF.19 In this communication we
have adopted simple, eco-friendly methodology for the development of amide and sulfonamide linked heterocycles
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directly by amidation and sulfonamidation of heteroaldehydes with heteroaryl amines and sulfonylamines.
Furan-2-carbaldehyde (1a), 1H-pyrrole-2-carbaldehyde (1b), thiophene-2-carbaldehyde (1c), isonicotinaldehyde
(1d), 3,5-dichloroisonicotinaldehyde (1e) were purchased from Sigma-Aldrich and used as such. 2,4-
Dichlorooxazole-5-carbaldehyde (1f), 2,4-dichlorothiazole-5-carbaldehyde (1g) were prepared by the reaction of
urea and thiourea with chloroacetic acid in the presence of conc. HCl followed by treatment with POCl3 in DMF.20
4-Phenyl-1H-imidazol-2-amine (2a) was obtained by the treatment of phenacyl bromide with acetyl guanidine in
DMF followed by hydrolysis in the presence of dil. H2SO4.17 4-Phenylthiazol-2-amine (2b) was prepared by the
reaction of phenacyl bromide with thiourea in methanol.17 N-(5-(Aminosulfonyl)-4-phenyl-1H-imidazol-2-
yl)benzamide (4) was prepared by the reaction of 4-phenyl-1H-imidazol-2-amine with benzoyl chloride followed
o
by chlorosulfonylation with sulfuryl chloride under ultrasonication in DMF at 0 C. The resultant N-(5-
(chlorosulfonyl)-4-phenyl-1H-imidazol-2-yl)benzamide on further treatment with 25% NH4OH gave 4.21 Initially,
in our attempt to develop amide linkage directly from aldehydes and amines, we have chosen 1a and 2a to carry
out the pilot reaction in the presence of different oxidants viz., m-CPBA in dichloromethane, H2O2 in dimethyl
carbonate (DMC) and CCl3CN/H2O2 in dichloromethane. From the data given in Table 1 it was found that
CCl3CN/H2O2 is the best oxidant resulting in the formation of product in 66%. In recent years, the use of green
reaction solvents such as ionic liquids and polyethylene glycol (PEG-400) has gained importance.22-24
Table 1. Oxidative amidation of 1a with 2a under different conditions
Entry
Oxidant
Solvent
Time
(h)
15
16
13
Yield
(%)
57
50
66
1
2
3
m-CPBA
H2O2
CCl3CN/H2O2
CH2Cl2
DMC
CH2Cl2
Though phase transfer catalysis is an alternative technique, it is not always possible because of sensitivity of the
reactants to aqueous conditions.25 In this context, PEG-400 has become an alternative reaction media to perform
organic synthesis due to its inherent advantages over toxic solvents. Moreover, PEG-400 is inexpensive, easy to
handle, thermally stable, non-toxic and recyclable. In order to increase the yield, the reaction between 1a and 2a
was carried out using PEG-400 in the presence of different oxidants m-CPBA, H2O2 and CCl3CN/H2O2. It was
noticed that CCl3CN/H2O2 in PEG-400 is the most favourable reaction conditions for direct amidation of
aldehydes with amines (Table 2). The mechanism for amidation of aldehydes with amines was proposed as
shown in scheme 1. The mechanism for oxidative amidation of aldehydes with amines is proposed as shown in
scheme 1. The addition of trichloromethylperoxyimidic acid (A) generated by the oxidation of
trichloroacetonitrile with hydrogen peroxide to imine followed by the elimination of trichloromethyl amide
resulted in 3a. The scope and generality of this reaction was subsequently examined using different
heteroaldehydes and heteroaryl amines and the products were obtained in excellent yield (Table 3). The
presence of electron withdrawing chloro substituent on heteroaldehydes increased the yield.
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This methodology was extended to prepare sulfonyl carboxamide linked heterocycles by the reaction of
heteroaldehydes with heteroaryl sulfonylamines (Table 4). Based on the obtained yield of the products it was
noticed that heteroaryl amines favors the reaction with the formation of products in high yield when compared
with heteroaryl sulfonylamines. This may be due to electron withdrawing effect of sulfonyl group.
Table 2. Oxidative amidation of 1a with 2a in PEG-400
Entry
Oxidant
Solvent
Time
(h)
12
14
10
Yield
(%)
62
58
84
1
2
3
m-CPBA
H2O2
CCl3CN/H2O2
PEG-400
PEG-400
PEG-400
Scheme 1. Plausible mechanism for the synthesis of amide by using CCl3CN/H2O2/PEG-400.
Table 3. Synthesis of heteroaryl amides from heteroaldehydes and heteroaryl amines
Entry
1
Aldehyde
Amine
Product
Yield
(%)
84 (3a)
(1a)
(2a)
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Table 3. Continued
Entry
Aldehyde
Amine
Product
Yield
(%)
2
3
1a
82 (3b)
(2b)
2a
85 (3c)
(1b)
4
5
1b
2b
2a
84 (3d)
83 (3e)
(1c)
1c
6
7
2b
2a
82 (3f)
82 (3g)
(1d)
8
9
1d
2b
2a
83 (3h)
91 (3i)
(1e)
10
11
1e
2b
2a
84 (3j)
92 (3k)
(1f)
12
1f
2b
90 (3l)
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Table 3. Continued
Entry
Aldehyde
Amine
Product
Yield
(%)
13
2a
91 (3m)
(1g)
14
1g
2b
89 (3n)
Table 4. Synthesis of heteroaryl sulfonyl carboxamides from heteroaldehydes and heteroaryl sulfonylamines
Entry
Aldehydes
1a
Sulfonylamines
Products
Yield
(%)
69 (5a)
1
(4)
68 (5b)
67 (5c)
2
3
4
5
1b
1c
1d
1e
4
4
4
4
70 (5d)
76 (5e)
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Table 4. Continued
Entry
Aldehydes
Sulfonylamines
4
Products
Yield
(%)
74 (5f)
6
1f
75 (5g)
7
1g
4
Conclusions
In conclusion we have reported a green protocol for direction amidation of heteroaldehydes with heteroaryl
amines / sulfonylamines in the presence of oxidant CCl3CN/H2O2 in PEG-400. The presence of electron
withdrawing substituents on heteroaldehydes increased the yield. Further heteroaryl amines favor the reaction
when compared with heteroaryl sulfonylamines.
Experimental Section
General. Melting points were determined in open capillaries on a Mel Temp apparatus and are uncorrected. The
IR spectra were recorded on a Thermo Nicolet IR 200 FT-IR spectrometer as KBr pellets and the wave numbers
1
were mentioned in cm-1. The H NMR and 13C NMR spectra were recorded in DMSO-d6 on a Jeol JNM
spectrometer operating at 400 and 100 MHz. All chemical shifts are reported in  (ppm) using TMS as an internal
standard. High-Resolution Mass spectra were recorded on Micromass Q-TOF mass spectrometer using
electrospray ionization. The microanalyses were performed on a Perkin-Elmer 240C elemental analyzer. The
progress of the reaction was monitored by TLC using silica gel plates and components were visualized under UV
light (254 and 365 nm).
General procedure for synthesis of amide from the reaction of aldehyde with amine. To a stirred solution of
aldehyde (1 mmol), amine (1 mmol), CCl3CN (2 mmol) in PEG-400 (5mL) at 0 oC, a solution of H2O2 (30%) (3mmol)
was added drop wise. Then the reaction mixture was stirred at room temperature for 8-12 h. After completion of
the reaction (monitored by TLC), the reaction mixture was poured into ice water (50 mL). The solid obtained was
filtered, washed with water and crude product was purified by column chromatography (silica gel, 60-120 mesh)
using hexane/ethylacetate (6:4) as eluent.
o
N-(4-Phenyl-1H-imidazol-2-yl)furan-2-carbo xamide (3a). White solid. mp 215-217 C. IR (KBr, νmax, cm–1): 1576
(C=N), 1609 (C=C), 1659 (CONH), 3357 (NH). 1H NMR (400 MHz, DMSO-d6): H 6.58 (t, 1H, C4-H, J 5.2 Hz), 7.10 (s,
1H, C5'-H), 7.38 (d, 1H, C3-H, J 5.2 Hz), 7.62-7.83 (m, 5H, Ar-H), 7.98 (d, 1H, C5-H, J 5.2 Hz), 8.96 (bs, 1H, O=C-NH),
12.44 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C 112.5 (C-4), 114.1 (C-3), 121.3 (C-5'), 127.2,
128.5, 128.9, 133.2 (aromatic carbons), 141.2 (C-4'), 141.8 (C-5), 146.8 (C-2'), 147.2 (C-2), 157.4 (C=O). HRMS:
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(m/z) 276.0760 [M+Na]+. Anal. Calcd. for C14H11N3O2: C, 66.40; H, 4.38; N, 16.59. Found: C, 66.46; H, 4.41; N,
16.66.
o
N-(4-Phenylthiazol-2-yl)furan-2-carboxamide (3b). White solid. mp 219-221 C. IR (KBr, νmax, cm–1): 1573 (C=N),
1603 (C=C), 1652 (CONH). 1H NMR (400 MHz, DMSO-d6): H 6.40 (t, 1H, C4-H, J 4.6 Hz), 7.19 (s, 1H, C5'-H), 7.45 (d,
1H, C3-H, J 4.6 Hz), 7.52 (d, 1H, C5-H, J 4.6 Hz), 7.54-7.87 (m, 5H, Ar-H), 10.28 (bs, 1H, CONH). 13C NMR (100 MHz,
DMSO-d6): C 108.6 (C-5'), 111.9 (C-4), 113.6 (C-3), 127.8, 128.1, 130.3, 134.5 (aromatic carbons), 144.6 (C-5),
148.2 (C-2), 150.4 (C-4'), 156.2 (C-2'), 157.2 (C=O). HRMS: (m/z) 293.0372 [M+Na]+. Anal. Calcd. for C14H10N2O2S:
C, 62.21; H, 3.73; N, 10.36. Found: C, 62.29; H, 3.68; N, 10.48.
o
N-(4-Phenyl-1H-imidazol-2-yl)-1H-pyrrole-2-carboxamide (3c). White solid. mp 214-216 C. IR (KBr, νmax, cm–1):
1575 (C=N), 1605 (C=C), 1648 (CONH), 3349, 3335 (NH). 1H NMR (400 MHz, DMSO-d6): H 6.38 (t, 1H, C4-H, J 4.8
Hz), 7.11 (s, 1H, C5'-H), 7.45 (d, 1H, C3-H, J 4.8 Hz), 7.49 (d, 1H, C5-H, J 4.8 Hz), 7.52-7.65 (m, 5H, Ar-H), 9.73 (bs,
1H, CONH), 11.02 (bs, 1H, NH-pyrrole), 12.50 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C 109.7 (C-
4), 111.8 (C-3), 121.5 (C-5'), 122.8 (C-5), 125.9 (C-2), 127.5, 128.7, 129.2, 133.5 (aromatic carbons), 141.7 (C-4'),
147.1 (C-2'), 157.5 (C=O). HRMS: (m/z) 275.0919 [M+Na]+. Anal. Calcd. for C14H12N4O: C, 66.65; H, 4.79; N, 22.21.
Found: C, 66.58; H, 4.72; N, 22.34.
o
N-(4-Phenylthiazol-2-yl)-1H-pyrrole-2-carboxamide (3d). White solid. mp 211-213 C. IR (KBr, νmax, cm–1): 1568
(C=N), 1607 (C=C), 1646 (CONH), 3346 (NH). 1H NMR (400 MHz, DMSO-d6): H 6.41 (t, 1H, C4-H, J 5.4 Hz), 7.18 (s,
1H, C5'-H), 7.48 (d, 1H, C3-H, J 5.4 Hz), 7.55 (d, 1H, C5-H, J 5.4 Hz), 7.62-7.75 (m, 5H, Ar-H), 11.06 (bs, 1H, NH-
pyrrole), 13.24 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): C 108.1 (C-5'), 110.2 (C-4), 112.1 (C-3), 123.4 (C-
5), 126.3 (C-2), 128.7, 129.7, 130.5, 134.5 (aromatic carbons), 150.8 (C-4'), 155.9 (C-2'), 157.7 (C=O). HRMS: (m/z)
292.0529 [M+Na]+. Anal. Calcd. for C14H11N3OS: C, 62.44; H, 4.12; N, 15.60. Found: C, 62.36; H, 4.08; N, 15.69.
o
N-(4-Phenyl-1H-imidazol-2-yl)thiophene-2-carboxamide (3e). White solid. mp 226-228 C. IR (KBr, νmax, cm–1):
1566 (C=N), 1599 (C=C), 1642 (CONH), 3342 (NH). 1H NMR (400 MHz, DMSO-d6): H 7.13 (s, 1H, C5'-H), 7.16 (t, 1H,
C4-H, J 5.0 Hz), 7.53-7.68 (m, 5H, Ar-H), 7.97 (d, 1H, C5-H, J 5.0 Hz), 8.28 (d, 1H, C3-H, J 5.0 Hz), 9.18 (bs, 1H,
CONH), 12.61 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C 121.8 (C-5'), 127.7, 128.2, 128.9, 129.3,
129.7, 130.2, 133.9 (aromatic carbons, C-4, C-5, C-3), 139.7 (C-2), 140.7 (C-4'), 146.2 (C-2'), 157.1 (C=O). HRMS:
(m/z) 292.0530 [M+Na]+. Anal. Calcd. for C14H11N3OS: C, 62.44; H, 4.12; N, 15.60. Found: C, 62.37; H, 4.16; N,
15.71.
o
N-(4-Phenylthiazol-2-yl)thiophene-2-carboxamide (3f). White solid. mp 223-225 C. IR (KBr, νmax, cm–1): 1562
(C=N), 1595 (C=C), 1638 (CONH). 1H NMR (400 MHz, DMSO-d6): H 7.19 (t, 1H, C4-H, J 4.4 Hz), 7.21 (s, 1H, C5'-H),
7.56-7.81 (m, 5H, Ar-H), 8.01 (d, 1H, C5-H, J 4.4 Hz), 8.32 (d, 1H, C3-H, J 4.4 Hz), 10.27 (bs, 1H, CONH). 13C NMR
(100 MHz, DMSO-d6): C 122.8 (C-5'), 128.4, 129.1, 130.4, 131.2, 131.7, 132.1, 133.2 (aromatic carbons, C-4, C-5,
C-3), 140.1 (C-2), 140.9 (C-4'), 146.5 (C-2'), 157.8 (C=O). HRMS: (m/z) 309.0124 [M+Na]+. Anal. Calcd. for
C14H10N2OS2: C, 58.72; H, 3.52; N, 9.78. Found: C, 58.80; H, 3.57; N, 9.68.
o
N-(4-Phenyl-1H-imidazol-2-yl)isonicotinamide (3g). White solid. mp 218-220 C. IR (KBr, νmax, cm–1): 1578 (C=N),
1
1612 (C=C), 1664 (CONH), 3364 (NH). H NMR (400 MHz, DMSO-d6): H 7.15 (s, 1H, C5'-H), 7.61-7.69 (m, 5H, Ar-
H), 8.02 (d, 2H, C3-H, C5-H, J 5.6 Hz), 8.84 (d, 2H, C2-H, C6-H, J 5.6 Hz), 10.88 (bs, 1H, CONH), 12.53 (bs, 1H, NH-
imidazole). 13C NMR (100 MHz, DMSO-d6): C 121.6 (C-3, C-5), 122.1 (C-5'), 128.8, 129.6, 130.4, 134.1 (aromatic
carbons), 140.6 (C-4), 142.7 (C-4'), 147.9 (C-2'), 149.8 (C-2, C-6), 164.3 (C=O). HRMS: (m/z) 287.0920 [M+Na]+.
Anal. Calcd. for C15H12N4O: C, 68.17; H, 4.58; N, 21.20. Found: C, 68.24; H, 4.56; N, 21.29.
o
N-(4-Phenylthiazol-2-yl)isonicotinamide (3h). White solid. mp 225-227 C. IR (KBr, νmax, cm–1): 1569 (C=N), 1610
(C=C), 1658 (CONH). 1H NMR (400 MHz, DMSO-d6): H 7.18 (s, 1H, C5'-H), 7.49-7.75 (m, 5H, Ar-H), 8.05 (d, 2H, C3-
H, C5-H, J 5.2 Hz), 9.06 (d, 2H, C2-H, C6-H, J 5.2 Hz), 12.74 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): C 122.1
(C-3, C-5), 123.4 (C-5'), 129.5, 129.8 130.2, 134.4 (aromatic carbons), 141.4 (C-4), 143.1 (C-4'), 148.1 (C-2'), 148.7
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(C-2, C-6), 164.6 (C=O). HRMS: (m/z) 304.0533 [M+Na]+. Anal. Calcd. for C15H11N3OS: C, 64.04; H, 3.94; N, 14.94.
Found: C, 64.15; H, 3.98; N, 14.81.
3,5-Dichloro-N-(4-phenyl-1H-imidazol-2-yl)isonicotinamide (3i). White solid. mp 234-236 oC. IR (KBr, νmax, cm–1):
1582 (C=N), 1619 (C=C), 1672 (CONH), 3366 (NH). 1H NMR (400 MHz, DMSO-d6): H 7.17 (s, 1H, C5'-H), 7.60-7.73
(m, 5H, Ar-H), 9.28 (s, 2H, C2-H, C6-H), 11.05 (bs, 1H, CONH), 12.57 (bs, 1H, NH-imidazole). 13C NMR (100 MHz,
DMSO-d6): C 122.4 (C-5'), 128.2, 129.6, 131.8, 132.7 134.3 (aromatic carbons, C-3, C-5), 142.3 (C-4), 143.4 (C-4'),
148.2 (C-2, C-6), 148.6 (C-2'), 164.8 (C=O). HRMS: (m/z) 355.0122 [M+Na]+. Anal. Calcd. for C15H10Cl2N4O:
C, 54.08; H, 3.03; N, 16.82. Found: C, 54.02; H, 3.00; N, 16.93.
o
3,5-Dichloro-N-(4-phenylthiazol-2-yl)isonicotinamide (3j). White solid. mp 238-240 C. IR (KBr, νmax, cm–1): 1579
1
(C=N), 1617 (C=C), 1666 (CONH). H NMR (400 MHz, DMSO-d6): H 7.24 (s, 1H, C5'-H), 7.66-7.88 (m, 5H, Ar-H),
9.31 (s, 2H, C2-H, C6-H), 13.04 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): C 109.1 (C-5'), 129.2, 130.1, 130.9,
133.3, 134.9 (aromatic carbons, C-3, C-5), 142.8 (C-4), 148.5 (C-2, C-6), 151.9 (C-4'), 157.1 (C-2'), 165.0 (C=O).
HRMS: (m/z) 344.0341 [M+Na]+. Anal. Calcd. for C15H9Cl2N3O: C, 51.44; H, 2.59; N, 12.00. Found: C, 51.52; H,
2.64; N, 11.91.
o
2,4-Dichloro-N-(4-phenyl-1H-imidazol-2-yl)oxazole-5-carboxamide (3k). White solid. mp 213-215 C. IR (KBr,
νmax, cm–1): 1588 (C=N), 1629 (C=C), 1672 (CONH), 3391 (NH). 1H NMR (400 MHz, DMSO-d6): H 7.20 (s, 1H, C5'-H),
7.61-7.78 (m, 5H, Ar-H), 9.27 (bs, 1H, CONH), 12.62 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C
122.9 (C-5'), 124.9 (C-4), 127.4, 128.5, 129.9, 134.7 (aromatic carbons), 138.4 (C-5), 144.5 (C-4'), 149.7 (C-2'),
151.3 (C-2), 165.4 (C=O). HRMS: (m/z) 344.9929 [M+Na]+. Anal. Calcd. for C13H8Cl2N4O2: C, 48.32; H, 2.50; N,
17.34. Found: C, 48.37; H, 2.54; N, 17.24.
2,4-Dichloro-N-(4-phenylthiazol-2-yl)oxazole-5-carboxamide (3l). White solid. mp 229-231 C. IR (KBr, νmax
cm–1): 1584 (C=N), 1627 (C=C), 1667 (CONH). H NMR (400 MHz, DMSO-d6): H 7.29 (s, 1H, C5'-H), 7.68-7.87 (m,
5H, Ar-H), 12.68 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): C 109.9 (C-5'), 125.3 (C-4), 129.5, 130.4, 130.9,
135.2 (aromatic carbons), 138.9 (C-5), 151.7 (C-2), 152.8 (C-4'), 158.3 (C-2'), 165.7 (C=O). HRMS: (m/z) 361.9543
[M+Na]+. Anal. Calcd. for C13H7Cl2N3O2S: C, 45.90; H, 2.07; N, 12.35. Found: C, 45.98; H, 2.10; N, 12.43.
o
,
1
o
2,4-Dichloro-N-(4-phenyl-1H-imidazol-2-yl)thiazole-5-carboxamide (3m). White solid. mp 233-235 C. IR (KBr,
νmax, cm–1): 1587 (C=N), 1625 (C=C), 1664 (CONH), 3382 (NH). 1H NMR (400 MHz, DMSO-d6): H 7.25 (s, 1H, C5'-H),
7.67-7.83 (m, 5H, Ar-H), 9.23 (bs, 1H, CONH), 12.68 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C
123.7 (C-5'), 128.9, 130.3, 131.4, 134.9, 135.4 (aromatic carbons, C-4), 144.6 (C-4'), 149.1 (C-5), 150.1 (C-2'),
153.4 (C-2), 161.4 (C=O). HRMS: (m/z) 360.9687 [M+Na]+. Anal. Calcd. for C13H8Cl2N4OS: C, 46.03; H, 2.38; N,
16.52. Found: C, 46.08; H, 2.42; N, 16.40.
2,4-Dichloro-N-(4-phenylthiazol-2-yl)thiazole-5-carboxamide (3n). White solid. mp 221-223 C. IR (KBr, νmax
o
,
cm–1): 1581 (C=N), 1621 (C=C), 1660 (CONH) cm–1. 1H NMR (400 MHz, DMSO-d6): H 7.37 (s, 1H, C5'-H), 7.72-7.91
(m, 5H, Ar-H), 12.64 (bs, 1H, CONH). 13C NMR (100 MHz, DMSO-d6): C 111.1 (C-5'), 130.1, 130.9, 131.4, 134.5,
135.7 (aromatic carbons, C-4), 149.2 (C-5), 152.9 (C-4'), 153.6 (C-2), 157.8 (C-2'), 161.7 (C=O). HRMS: (m/z)
377.9317 [M+Na]+. Anal. Calcd. for C13H7Cl2N3OS2: C, 43.83; H, 1.98; N, 11.80. Found: C, 43.75; H, 1.92; N, 11.89.
N-((2-Benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)furan-2-carboxamide (5a). Pale yellow solid. mp 245-247
1
oC. IR (KBr, νmax, cm–1): 1120, 1318 (SO2), 1594 (C=N), 1640 (C=C), 1651, 1668 (CONH), 3382 (NH). H NMR (400
MHz, DMSO-d6): H 6.63 (t, 1H, C4-H, J 4.8 Hz), 7.46 (d, 1H, C3-H, J 4.8 Hz), 7.56-7.66 (m, 10H, Ar-H), 8.01 (d, 1H,
C5-H, J 4.8 Hz), 11.04 (bs, 1H, CONH), 11.19 (bs, 1H, NHSO2), 12.52 (bs, 1H, NH-imidazole). 13C NMR (100 MHz,
DMSO-d6): C 113.2 (C-4), 114.4 (C-3), 127.1, 127.8, 128.1, 129.1. 129.5, 130.3, 130.7, 133.3, 135.5 (aromatic
carbons, C-5'), 138.5 (C-4'), 142.5 (C-5), 147.8 (C-2), 152.9 (C-2'), 160.1 (CONH), 161.3 (CONHSO2). HRMS: (m/z)
459.0731 [M+Na]+. Anal. Calcd. for C21H16N4O5S: C, 57.79; H, 3.70; N, 12.84. Found: C, 57.85; H, 3.76; N, 12.91.
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N-((2-Benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)-1H-pyrrole-2-carboxamide (5b). Pale yellow solid. mp
o
241-243 C. IR (KBr, νmax, cm–1): 1123, 1321 (SO2), 1591 (C=N), 1635 (C=C), 1654, 1663 (CONH), 3354, 3368 (NH).
1H NMR (400 MHz, DMSO-d6): H 6.42 (t, 1H, C4-H, J 5.2 Hz), 7.49 (d, 1H, C3-H, J 5.2 Hz), 7.58 (d, 1H, C5-H, J 5.2
Hz), 7.64-8.01 (m, 10H, Ar-H), 11.07 (bs, 1H, NH-pyrrole), 11.11 (bs, 1H, CONH), 12.32 (bs, 1H, NHSO2), 12.55 (bs,
1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C 110.6 (C-4), 112.1 (C-3), 123.4 (C-5), 126.3 (C-2), 127.5,
127.9, 128.6, 128.9, 129.4, 131.2, 131.5, 133.1, 134.7 (aromatic carbons, C-5'), 138.9 (C-4'), 153.6 (C-2'), 160.5
(CONH), 162.8 (CONHSO2). HRMS: (m/z) 458.0890 [M+Na]+. Anal. Calcd. for C21H17N5O4S: C, 57.92; H, 3.94; N,
16.08. Found: C, 57.99; H, 4.00; N, 16.15.
N-((2-Benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)thiophene-2-carboxamide (5c). Pale yellow solid. mp 239-
o
1
241 C. IR (KBr, νmax, cm–1): 1131, 1325 (SO2), 1589 (C=N), 1631 (C=C), 1658, 1661 (CONH), 3361 (NH). H NMR
(400 MHz, DMSO-d6): H 7.19 (t, 1H, C4-H, J 5.6 Hz), 7.61-7.85 (m, 10H, Ar-H), 7.99 (d, 1H, C5-H, J 5.6 Hz), 8.31 (d,
1H, C3-H, J 5.6 Hz), 11.15 (bs, 1H, CONH), 11.78 (bs, 1H, NHSO2), 12.65 (bs, 1H, NH-imidazole). 13C NMR (100
MHz, DMSO-d6): C 126.9 (C-3), 127.3, 127.9, 128.3, 128.7, 129.1, 130.3, 130.9, 131.2, 132.7, 133.5, 134.2
(aromatic carbons, C-4, C-5, C-5'), 138.7 (C-4'), 140.5 (C-2), 153.1 (C-2'), 159.7 (CONH), 161.4 (CONHSO2). HRMS:
(m/z) 475.0519 [M+Na]+. Anal. Calcd. for C21H16N4O4S2: C, 55.74; H, 3.56; N, 12.38. Found: C, 55.79; H, 3.61; N,
12.43.
o
N-((2-Benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)isonicotinamide (5d). Pale yellow solid. mp 246-248 C. IR
(KBr, νmax, cm–1): 1134, 1327 (SO2), 1598 (C=N), 1641 (C=C), 1662, 1670 (CONH), 3389 (NH). H NMR (400 MHz,
1
DMSO-d6): H 7.70-8.02 (m, 10H, Ar-H), 8.05 (d, 2H, C3-H, C5-H, J 5.3 Hz), 8.89 (d, 2H, C2-H, C6-H, J 5.3 Hz), 11.18
(bs, 1H, CONH), 11.85 (bs, 1H, NHSO2), 12.61 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C 123.1 (C-
3, C-5), 127.4, 127.9, 128.0, 128.1, 129.8, 131.5, 132.4, 133.4, 134.9 (aromatic carbons, C-5'), 140.3 (C-4'), 141.8
(C-4), 150.4 (C-2, C-6), 154.5 (C-2'), 165.2 (CONH), 166.7 (CONHSO2). HRMS: (m/z) 470.0881 [M+Na]+. Anal. Calcd.
for C22H17N5O4S: C, 59.05; H, 3.83; N, 15.65. Found: C, 59.11; H, 3.80; N, 15.73.
N-((2-Benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)-3,5-dichloroisonicotinamide (5e). Pale yellow solid. mp
o
1
264-266 C. IR (KBr, νmax, cm–1): 1129, 1332 (SO2), 1601 (C=N), 1645 (C=C), 1668, 1679 (CONH), 3390 (NH). H
NMR (400 MHz, DMSO-d6): H 7.74-8.11 (m, 10H, Ar-H), 9.32 (s, 2H, C2-H, C6-H), 11.24 (bs, 1H, CONH), 11.88 (bs,
1H, NHSO2), 12.67 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C 127.5, 127.9, 128.2, 128.6, 128.9,
129.5, 130.0, 131.9, 133.7, 134.1, 134.5 (aromatic carbons, C-3, C-5, C-5'), 141.1 (C-4'), 143.9 (C-4), 148.7 (C-2, C-
6), 156.1 (C-2'), 165.6 (CONH), 167.1 (CONHSO2). HRMS: (m/z) 538.0128 [M+Na]+. Anal. Calcd. for
C22H15Cl2N5O4S: C, 51.17; H, 2.93; N, 13.56. Found: C, 51.24; H, 2.99; N, 13.50.
N-((2-Benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)-2,4-dichlorooxazole-5-carboxamide (5f). Pale yellow
o
solid. mp 258-260 C. IR (KBr, νmax, cm–1): 1142, 1342 (SO2), 1608 (C=N), 1648 (C=C), 1678, 1685 (CONH), 3398
1
(NH) cm–1. H NMR (400 MHz, DMSO-d6): H 7.76-8.13 (m, 10H, Ar-H), 11.23 (bs, 1H, CONH), 11.94 (bs, 1H,
NHSO2), 12.70 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C 126.8 (C-4), 127.6, 127.9, 128.6, 129.1,
129.6, 130.7, 134.6, 134.9, 135.4 (aromatic carbons, C-5'), 140.2 (C-5), 142.6 (C-4'), 153.3 (C-2), 153.9 (C-2'),
166.1 (CONH), 167.9 (CONHSO2). HRMS: (m/z) 527.9921 [M+Na]+. Anal. Calcd. for C20H13Cl2N5O5S: C, 47.44; H,
2.59; N, 13.83. Found: C, 47.51; H, 2.55; N, 13.89.
N-((2-Benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)-2,4-dichlorothiazole-5-carboxamide (5g). Pale yellow
o
solid. mp 270-272 C. IR (KBr, νmax, cm–1): 1139, 1335 (SO2), 1605 (C=N), 1642 (C=C), 1680, 1681 (CONH), 3395
1
(NH). H NMR (400 MHz, DMSO-d6): H 7.85-8.07 (m, 10H, Ar-H), 11.28 (bs, 1H, CONH), 12.05 (bs, 1H, NHSO2),
12.74 (bs, 1H, NH-imidazole). 13C NMR (100 MHz, DMSO-d6): C 127.3, 127.9, 128.2, 128.6, 129.0, 129.4, 130.9,
131.8, 135.1, 135.5 (aromatic carbons, C-5, C-5'), 139.2 (C-4), 139.4 (C-4'), 145.7 (C-2), 153.9 (C-2'), 162.8
(CONH), 164.2 (CONHSO2). HRMS: (m/z) 543.9693 [M+Na]+. Anal. Calcd. for C20H13Cl2N4O5S2: C, 45.99; H, 2.51; N,
13.41. Found: C, 45.94; H, 2.57; N, 13.46.
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Acknowledgements
One of the authors G. Lakshmi Teja is indebted to University Grants Commission (UGC), New Delhi for sanction of
UGC-BSR fellowship.
Supplementary Material
1H NMR, 13C NMR and HRMS Spectra for compounds N-(4-phenyl-1H-imidazol-2-yl)furan-2-carboxamide (3a), N-
(4-phenyl-1H-imidazol-2-yl)isonicotinamide (3g), N-((2-benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)furan-2-
carboxamide (5a) and N-((2-Benzamido-4-phenyl-1H-imidazol-5-yl)sulfonyl)-2,4-dichlorothiazole-5-carboxamide
(5g) can be found using the link "Supplementary Material" in the journal issue contents page.
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