Microwave-assisted synthesis of (2-butyl-5-nitrobenzo[b]furan-3-yl)-[4-(substituted ethynyl)phenyl]methanones

Article abstract of DOI:10.24820/ark.5550190.p010.681

We report a new method for the efficient and rapid synthesis of (2-butyl-5-nitrobenzo[b]furan-3-yl)[4- (substituted ethynyl)phenyl]methanones using a Pd-Cu catalyzed microwave-assisted Sonogashira coupling reaction. In comparison to the conventional heating procedure, the time of synthesis and effort are significantly reduced in the present method, without side-product formation. Microwave irradiation considerably accelerated the formation of (2-butyl-5-nitrobenzo[b]furan-3-yl)[4-(substituted ethynyl)phenyl]methanone analogues.

Full text of DOI:10.24820/ark.5550190.p010.681

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Microwave-assisted synthesis of
(2-butyl-5-nitrobenzo[b]furan-3-yl)-[4-(substituted ethynyl)phenyl]methanones
Nilesh D. Parmar, Sanjay D. Hadiyal, Vimal H. Kapupara, and Hitendra S. Joshi*
Department of Chemistry, Saurashtra University, Rajkot-360 005, Gujarat, India
Email: parmarnilesh1117@gmail.com, drhsjoshichem@gmail.com
Received 07-06-2018
Accepted 08-30-2018
Published on line 09-13-2018
Abstract
We report a new method for the efficient and rapid synthesis of (2-butyl-5-nitrobenzo[b]furan-3-yl)[4-
(substituted ethynyl)phenyl]methanones using a Pd-Cu catalyzed microwave-assisted Sonogashira coupling
reaction. In comparison to the conventional heating procedure, the time of synthesis and effort are
significantly reduced in the present method, without side-product formation. Microwave irradiation
considerably
accelerated
the
formation
of
(2-butyl-5-nitrobenzo[b]furan-3-yl)[4-(substituted
ethynyl)phenyl]methanone analogues.
R
H
cat. [Pd(0)]
O
O
Cu(Xantphos)I
co-catalyst
O2N
O2N
Microwave
110 °C, 5-10 min
O
O
OTf
R
Keywords: Benzo[b]furan, Sonogashira approach, microwave-assisted synthesis
DOI: https://doi.org/10.24820/ark.5550190.p010.681
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Introduction
Oxygen containing heterocycles form one of the largest group of compounds in organic chemistry. Among
them, one of the most important are benzo[b]furans, a class of fused-ring heterocyclic compounds. Several
derivatives of benzo[b]furan have been recognized as biologically and pharmacologically relevant molecules.1
Benzo[b]furan derivatives exhibit significant activity against various therapeutic areas including antifungal,2
antitubercular,3 antiinflammatory,4 anticonvulsant,5 anticancer,6 anti-HIV,7 analgesic,8 antiparasitic,9
antihyperlipidemic,10 antioxidant,11 antidiabetic,12 antihypertensive,13 hypotensive,14 arrhythmic activities,15
and so on. Additionally, such heterocyclic compounds are found in various branches of chemical research,
such as in polymer,16 dyes industries,17 and in silver photography.18 Benzo[b]furan derivatives are important
heterocycles which are frequently found as both bioactive compounds and organic materials. The
benzo[b]furan moiety is found in structurally simple drugs like Ramelteon19 I, Amiodarone20 II, Vilazodone21 III,
Dronedarone22 IV, Pyridylbenzofuran23 V, Methoxsalen24 VI (Figure 1). Although microwave assisted and
numerous synthetic approaches have been developed to prepare this family of compounds during the past
decades, general protocols for the synthesis of these compounds are still of high interest.25-27
Figure 1 Representative examples of some drugs containing the benzo[b]furan moiety.
The palladium catalyzed coupling of terminal acetylenes with aryl triflates (the Sonogashira cross-coupling
reaction) is an effective and widely-used method to form new carbon-carbon bonds.28,29 At present, the
Sonogashira reaction has been widely used to couple a terminal sp-hybridized carbon of an alkyne with an sp2
carbon of an aryl or vinyl halide (or triflate),30,31 It also plays a key role in the synthesis of many natural
products,32 pesticides, pharmaceuticals33 and new materials and nano-molecular devices.34 Since the discovery
of the Sonogashira reactions, the most widely used catalysts are Pd-type compounds. Many cross-coupling
reactions catalyzed by Pd/Cu co-catalyst involve cross-coupling of a terminal alkyne with a halogenated or
triflyloxy-benzene, however the reactions coupling of terminal alkynes with halogenated or trifloxy
heterocycles have been investigated in very few numbers.
Microwave irradiation is used to promote chemical reactions, and a number of reviews have advocated
the use of microwave technology in organic synthesis.35 Microwaves provide a powerful way to carry out
synthetic chemistry and the ability of microwaves to shorten reaction times, increase reaction yields and to
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facilitate reactions that are otherwise unsuccessful under conventional conditions, are properties that
medicinal chemists often look for to optimize their everyday procedures.36
Herein, we report a synthesis of novel (2-butyl-5-nitrobenzo[b]furan-3-yl)[4-(substituted ethynyl)phenyl]-
methanones employing an environment-friendly microwave irradiation method via benzo[b]furan derivatives
as intermediates.
Results and Discussion
The synthesis of the title compounds was carried out by both microwave irradiation and conventional heating
procedures as shown in Scheme 1. 2-(Bromomethyl)-4-nitrophenol (1) was taken as starting material. The first
step involved formation of 2-butyl-5-nitrobenzo[b]furan (2) from 1 in a two-step in situ synthesis, where firstly
triphenylphosphine in DCM as solvent was added, followed by reflux for one hour, then triethylamine and
pentanoyl chloride were added and the mixture heated at reflux in toluene for three hours to form 2-butyl-5-
nitrobenzo[b]furan (2) in 95% yield.
O
1. PPh3, CH2Cl2
reflux, 1 h
OH
Br
O
SnCl4 (L.A.)
O2N
2. pentanoyl chloride
TEA, PhMe
4-HOC6H4COCl
0 °C to rt, 2 h
O2N
O2N
O
reflux, 3 h
OH
1
2
3
,
t
r
O
2
o
t
f
T
C
°
h
0
3
R
H
O
Pd(PPh3)2Cl2
DIPEA
O
O2N
O2N
Cu(Xantphos)I
microwave
110 °C, 5-10 min
O
OTf
O
R
5a-k
4
Scheme 1
In the next step, a Friedel–Crafts acylation reaction on 2 using SnCl4 as Lewis acid with 4-hydroxybenzoyl
chloride in dichloromethane as a solvent at 0 oC to rt for two hours gave (2-butyl-5-nitrobenzo[b]furan-3-yl)(4-
hydroxyphenyl)methanone (3) in 88% yield. Subsequent triflate formation using trifluoromethanesulfonic
o
anhydride (Tf2O) in dichloromethane with pyridine as a base at 0 C to rt for three hours, provided 4-(2-butyl-
5-nitrobenzo[b]furan-3-carbonyl)phenyl trifluoromethanesulfonate (4) in 88% yield. The structures of
compounds 3 and 4 were confirmed by 1H NMR, mass spectra and elemental analyses.
Sonogashira coupling of the triflate 4 with various substituted terminal acetylene derivatives under
microwave irradiation and conventional heating, followed by simple work-up yielded (2-butyl-5-
nitrobenzo[b]furan-3-yl)[4-(substituted ethynyl)phenyl]methanones (5a-k). The microwave irradiation
provided excellent yields compared to conventional heating. The structures of compounds 5a-k were
1
characterized by various spectroscopic techniques such as FT-IR, H NMR, 13C NMR, mass spectral and
elemental analyses; e.g. the IR spectrum of compounds 5a, 5b, 5c, 5d, 5e, 5h, 5j, and 5k showed an acetylenic
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1
band at 2220 cm-1, and C=O stretching at 1630 cm-1 ; the H NMR spectrum of all products showed signals in
the aromatic region, between or near about 7-8 ppm and in the aliphatic region in between or near about 0-3
ppm ; the 13C NMR spectrum of compound 5b, 5c, 5d, 5e, 5f, 5g, 5i, and 5j showed acetylenic carbons in the
regions 91-98 and 75-88 ppm. LC-MS analysis of compounds 5a and 5b showed 100% purity. The mass spectra
and C, H, N analysis results of all compounds are in agreement with the assigned structures. The reaction
times and yields of compounds 5a-k by microwave and conventional methods are given in Table 1.
The acetylenes with aliphatic substituents (entries 5f, 5g, 5h and 5i) were formed in slightly higher yields
o
than those with aromatic substituents (entry- 5a, 5b, 5c, 5d, 5e and 5j) under microwave irradiation at 110 C
and 70-80 W for 5-10 minute in a sealed vessel, as compared with the conventional heating. Compound 5k
o
was formed in higher yield by both microwave and conventional methods at 80 C, compared to all other
compounds due to the use of trimethylsilylacetylene. Formation of all the desired compounds was accelerated
by microwave irradiation, being obtained in 5-10 minutes with higher yields as compared with the
conventional heating method.
Table 1. Synthesis of compounds 5a-k by microwave and conventional heating
Microwave
Conventional heating
irradiation
Comp.
R
Time
(Min)
10
Time
(Min)
10
Yield (%)
Yield (%)
5a
5b
5c
5d
5e
5f
5g
5h
5i
4-tolyl
2-fluorophenyl
phenyl
4-n-propylphenyl
4-fluorophenyl
cyclopropyl
cyclopentyl
cyclohexyl
n-pentyl
79
83
88
81
85
91
90
87
93
81
94
-
3
10
10
10
10
4
10
10
3
10
10
3
10
05
6
10
05
7
10
05
5
10
05
8
10
5j
5k
4-ethylphenyl
H
10
8
10
05
10
Conclusions
In conclusion, we report a simple, efficient, rapid and environment-friendly method for the synthesis of novel
(2-butyl-5-nitrobenzo[b]furan-3-yl)[4-(substituted ethynyl)phenyl]methanones employing various acetylene
substrates using microwave-assisted Pd-catalysed and Cu(Xantphos)I co-catalysed Sonogashira coupling
reactions. The advantages of microwave irradiation were avoidance of the formation of side products, and
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also useful in the case of catalyst, to avoid the formation of palladium oxide and triphenylphosphine oxide
(TPPO) complex. Furthermore, we found that the reaction is generally tolerant of all electron-withdrawing,
electron-donating, aromatic and aliphatic substituents. The structures of all compounds were supported by
1
mass and elemental analyses as well as spectral data such as FT-IR and H NMR, and some of the compounds
were characterized by 13C NMR and LC-MS analysis. The straightforward synthesis of these compounds from
readily available starting materials should open a new access for novel benzo[b]furan heterocycles with
potentially interesting biological and pharmaceutical activities.
Experimental Section
General. All purchased chemicals were used without further purification. Reactions were monitored by thin
layer chromatography (TLC) on silica gel-G plates (G60 F254 (Merck)) of 0.5 mm thickness, visualizing with
ultraviolet light (254 and 365 nm), or with iodine vapor or aq. KMnO4. Melting points were determined using a
Buchi B-540 capillary apparatus. IR data were recorded on a Shimadzu FT-IR-8400 instrument using DRS
(diffusive reflectance system) method and are reported in cm-1 (KBr). NMR spectra were recorded on a Bruker
1
Avance 400 MHz spectrometer (400 MHz for H NMR and 101 MHz for 13C NMR) respectively in deuterated
solvents like CDCl3 or DMSO-d6 and chemical shifts are referenced to the solvent residual signals with respect
to tetramethylsilane; 1H NMR chemical shifts are designated using the following abbreviations as well as their
combinations: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad signal, coupling
constants in Hz. Elemental analysis was carried out on Euro EA 3000 elemental analyser and the results are in
agreement with the structures assigned. Microwave experiments were carried out in an Anton-Paar
Monowave 300 synthesizer using borosilicate glass G10 vial sealed with PTFE-coated silicone septum. The
control of reaction temperature was monitored by ruby thermometer. Mass spectra were recorded on a
Shimadzu GC-MS-QP-2010 mass spectrometer in ESI (70eV) model using direct inlet probe technique and m/z
is reported in atomic units per elementary charge. Solvents were evaporated with a Büchi rotary evaporator.
Purification was performed by column chromatography using silica gel 40-63 µm (230-400 mesh size), and
borosil glass column having a length about 1000 mm.
2-Butyl-5-nitrobenzo[b]furan (2). A mixture of 2-hydroxy-5-nitrobenzyl bromide 1 (5.0 g, 21.5 mmol),
triphenylphosphine (5.65 g, 21.5 mmol) and dichloromethane (80 mL) was heated to reflux for 1 h. On cooling
to rt, a white precipitate of phosphonium bromide salt separated. To the phosphonium bromide in toluene
(100 mL), was added triethylamine (7.5 mL, 53 mmol) and pentanoyl chloride (5.19 g, 43 mmol). The mixture
was heated and stirred under reflux for 3 h. After completion of the reaction (checked by TLC), It was allowed
to cool, the triphenylphosphine oxide formed was filtered off, and washed with EtOAc and the filtrate was
concentrated in vacuo. The viscous residue obtained is dissolved in water and extracted with EtOAc. The
combined organic layers was dried over anhydrous Na2SO4 and the solvent removed to provide 2-butyl-5-
nitrobenzo[b]furan (2) as a light yellow liquid. [C12H13NO3; bp.: 318-320 oC (760 mmHg); Yield: 4.5 g, 94%].
(2-Butyl-5-nitrobenzo[b]furan-3-yl)(4-hydroxyphenyl)methanone (3). 2-Butyl-5-nitrobenzo[b]furan 2 (4.5 g,
20.5 mmol), 4-hydroxybenzoyl chloride (3.84 g, 24.6 mmol) and dichloromethane (40 mL) were stirred
together to obtain a homogeneous solution. The flask was cooled in an ice-bath and SnCl4 (4.8 mL, 41.0 mmol)
was added dropwise, with stirring. The mixture was stirred for 30 min with ice cooling and then for 2 h at rt.
After completion of the reaction (checked on TLC), the mixture was poured into ice cold water and extracted
with CH2Cl2 (20 mL × 2). The organic layer washed with saturated aq. NaHCO3 (30 mL × 2). The combined
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organic layer was dried over anhydrous Na2SO4 and the solvent was removed in a Büchi evaporator to obtain
a crude solid, titurated with Et2O (10 mL × 3) to obtain (2-butyl-5-nitrobenzo[b]furan-3-yl)(4-hydroxy-
o
1
phenyl)methanone (3) as a white solid. [C18H15NO5; mp.: 91-93 C; Yield: 5.9 g, 88%]. H NMR (400 MHz,
DMSO-d6): δ 10.58 (s, 1H), 8.25 (d, J 7.6 Hz, 2H), 7.92 (d, J 8.4 Hz, 1H), 7.74 (d, J 8.0 Hz, 2H), 6.92 (d, J 8.4 Hz,
2H), 2.85 (t, J 7.4 Hz, 2H), 1.68 (t, J 7.4 Hz, 2H), 1.23 (t, J 7.4 Hz, 2H), 0.81 (t, J 7.2 Hz, 3H); MS: m/z (M+) 339;
Anal. Calc. for C19H17NO5: C, 67.25; H, 5.05; N, 4.13; Found: C, 67.16; H, 5.01; N, 4.03%.
4-(2-Butyl-5-nitrobenzo[b]furan-3-carbonyl)phenyl trifluoromethanesulfonate (4). A mixture of (2-butyl-5-
nitrobenzo[b]furan-3-yl)(4-hydroxyphenyl)methanone 3 (5.9 g, 17.3 mmol), pyridine (4.19 mL, 52.1 mmol) and
CH2Cl2 (80 mL) was stirred and cooled in an ice bath. Trifluoromethanesulfonic anhydride (8.8 mL, 52.1 mmol)
was added dropwise under nitrogen. The mixture was stirred for 10 min at the same temperature and then for
3 h at rt. After completion of the reaction (checked by TLC), the mixture was poured into 1N aqueous HCl (150
mL) and extracted with EtOAc (50 mL × 2). The combined organic layer was dried over anhydrous Na2SO4 and
the
solvent
was
removed
to
give
4-(2-butyl-5-nitrobenzo[b]furan-3-carbonyl)phenyl
trifluoromethanesulfonate (4) as a light yellow liquid. [C20H16F3NO7S; bp.: 232-234 oC (760 mmHg); Yield: 7.2 g,
87%]. 1H NMR (400 MHz, DMSO-d6): δ 8.30-8.26 (m, 1H), 8.02-7.99 (m, 2H), 7.94 (d, J 8.8, 1H), 7.76 (t, J 4.4 Hz,
2H), 2.76 (t, J 7.6 Hz, 2H), 1.71-1.63 (m, 2H), 1.28-1.19 (m, 2H), 0.81 (t, J 6.6 Hz, 3H); MS: m/z (M+) 471; Anal.
Calc. for C20H16F3NO7S: C, 50.96; H, 3.42; N, 2.97; Found: C, 50.81; H, 3.35; N, 2.84%.
General procedure for synthesis of (2-butyl-5-nitrobenzo[b]furan-3-yl)[4-(substituted ethynyl)phenyl]-
methanones (5a-k)
Microwave irradiation (MW) method. In a 10 mL dry microwave glass vial were placed 4-(2-butyl-5-
nitrobenzo[b]furan-3-carbonyl)phenyl trifluoromethanesulfonate (4) (150 mg, 0.31 mmol), Cu(Xantphos)I (48
mg, 0.06 mmol), DIPEA (0.19 mL, 1.11 mmol), DMF (5 mL) and the acetylene substrate (0.63 mmol). The
mixture was degassed by purging with N2 gas for 20 min and then bis(triphenylphosphine)palladium(II)-
dichloride was added as catalyst, with further degassing for 10 min. The vial was sealed, placed in the
microwave chamber and stirred at 600 rpm, 70-80 W and at 110 oC for 5-10 min. The reaction mixture was
then cooled to rt, then the vial was opened and completion of reaction was checked by TLC. The reaction mass
was poured into ice-cold water (20 mL) and extracted with EtOAc (20 mL × 2), the organic layer was washed
with brine (25 mL × 2). The combined organic layer was dried over anhydrous Na2SO4 and the solvent was
removed on a Büchi evaporator to obtain a crude solid product. Purification was effected by column
chromatography (silica gel) using n-hexane:EtOAc (9:1) as eluent to afforded pure (2-butyl-5-
nitrobenzo[b]furan-3-yl)[4-(substituted ethynyl)phenyl]methanones 5a-k.
Conventional heating (CH) method. In a 10 mL glass vial was added 4-(2-butyl-5-nitrobenzo[b]furan-3-
carbonyl)phenyl trifluoromethanesulfonate (4) (150 mg, 0.31 mmol), Cu(Xantphos)I (48 mg, 0.06 mmol), DIPEA
(0.19 mL, 1.11 mmol), DMF (5 mL), and the acetylene substrate (0.63 mmol). The mixture was degassed by
purging with N2 gas for 20 min then bis(triphenylphosphine)palladium(II)dichloride was added as co-catalyst,
with further degassing for 10 min. The mixture was stirred at 110 oC for 10 min. The reaction mixture was then
cooled to rt and completion of reaction was checked by TLC. The mixture was poured into ice cold water (20
mL) and extracted with EtOAc (20 mL × 2), the organic layer was washed with brine (25 mL × 2). The combined
organic layer was dried on anhydrous Na2SO4 and the solvent was removed to give a crude solid product.
Purification of the crude solid was carried out by column chromatography using n-hexane:EtOAc (9:1) as
eluent system to afford pure (2-butyl-5-nitrobenzo[b]furan-3-yl)[4-(substituted ethynyl)phenyl]methanones
5a-k.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)[4-(p-tolylethynyl)phenyl]methanone (5a). Light yellow solid; Yield: MW
o
79%; mp.: 79-81 C; IR (KBr, νmax, cm-1): 3107 (νC=C aromatic), 2951 (νC-H aliphatic), 2210 (νCC, disubstituted),
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1637 (νC=O), 1597 (νC=C aromatic), 1519 (νNO asymmetric), 1450 (νC=C aromatic), 1404 (δC-H), 1342 (νNO
2
2
), 1265 (ν=C-O-C asymmetric), 1057 (ν=C-O-C symmetric), 1082 (δC-H aromatic), 810 (δCH p-disubstituted
symmetric
aromatic); 1H NMR (400 MHz, CDCl3): δ 8.39 (d, J 2.0 Hz, 1H), 8.24 (dd, J 2.4, 9.2 Hz, 1H), 7.81 (d, J 8.4 Hz, 2H),
7.66 (d, J 8.4 Hz, 2H), 7.58 (d, J 9.2 Hz, 1H), 7.47 (d, J 8.0 Hz, 2H), 7.19 (d, J 8.0 Hz, 2H), 2.90 (t, J 15.6 Hz, 2H),
2.39 (s, 3H), 1.75 (qt, J 7.6, 14.8 Hz, 2H), 1.35 (qt, J 7.6, 14.8 Hz, 2H), 0.90 (t, J 14.8 Hz, 3H); MS: m/z [M+] 437;
LC-MS: RT: 1.486 min., 100%; Anal. Calc. for C28H23NO4: C, 76.87; H, 5.30; N, 3.20; Found: C, 76.84; H, 5.25; N,
3.17%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl){4-[(2-fluorophenyl)ethynyl]phenyl}methanone (5b). White solid; Yield:
o
MW 83%, CH 3%; mp.: 77-79 C; IR (KBr, νmax, cm-1): 3101 (νC-H aromatic), 2955 (νC-H aliphatic), 2218 (νCC
,
disubstituted), 1651 (νC=O), 1595 (νC=C aromatic), 1531 (νNO asymmetric) 1448 (νC=C aromatic), 1402 (δC-H), 1342
2
(νNO symmetric), 1255 (ν=C-O-C asymmetric), 1057 (ν=C-O-C symmetric), 1080 (δC-H aromatic), 842 (νC-F ), 756 (δCH
2
1
o-disubstituted aromatic); H NMR (400 MHz, DMSO-d6): δ 8.27 (d, J 10.8 Hz, 2H), 7.93 (d, J 8.8 Hz, 1H), 7.87
(d, J 8.0 Hz, 2H), 7.77 (d, J 7.6 Hz, 2H), 7.69 (t, J 6.6 Hz , 1H), 7.53 (d, J 5.6 Hz, 1H), 7.38 (t, J 9.0 Hz, 1H), 2.82 (t, J
7.0 Hz, 2H), 1.68 (t, J 6.8 Hz, 2H), 1.24 (qt, J 6.8, 13.6 Hz, 2H), 0.799 (t, J 7.0 Hz, 3H); 13C-NMR (101 MHz, DMSO-
d6): δ 189.5, 168.1, 163.1, 160.6, 155.9, 144.2, 138.1, 133.6, 131.8, 131.6, 129.2, 127.0, 126.4, 124.9, 124.9,
120.6, 117.0, 116.4, 115.9, 115.7, 112.3, 110.1, 110.0, 93.3, 85.6, 29.1, 27.5, 21.6, 13.3; MS: m/z [M+] 441; LC-
MS: RT: 2.689 min., 100%; Anal. Calc. for C22H20FNO4: C, 73.46; H, 4.57; N, 3.17; Found: C, 73.42; H, 4.52; N,
3.14%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)[4-(phenylethynyl)phenyl]methanone (5c). White solid; Yield: MW 88%,
o
CH 4%; mp.: 81-83 C; IR (KBr, νmax, cm-1): 3103 (νC-H aromatic), 2955 (νC-H aliphatic), 2214 (νCC, disubstituted),
1647 (νC=O), 1599 (νC=C aromatic), 1523 (νNO asymmetric), 1448 (νC=C aromatic), 1402 (δC-H), 1340 (νNO
2
2
1
), 1253 (ν=C-O-C asymmetric), 1064 (ν=C-O-C symmetric), 1080 (δC-H aromatic); H NMR (400 MHz,
symmetric
DMSO-d6): δ 8.27 (d, J 9.2 Hz, 2H), 7.94 (d, J 8.8 Hz, 1H), 7.86 (d, J 7.2 Hz, 2H), 7.76 (d, J 7.6 Hz, 2H), 7.62 (s,
2H), 7.47 (s, 3H), 2.82 (s, 2H), 1.67 (d, J 6.4 Hz, 2H), 1.24 (d, J 6.8 Hz, 2H), 0.80 (t, J 6.6 Hz, 3H); 13C-NMR (101
MHz, DMSO-d6): δ 189.5, 168.1, 155.9, 144.2, 137.8, 131.7, 131.6, 129.3, 129.2, 128.8, 127.1, 127.0, 121.6,
120.6, 117.0, 116.4, 112.3, 92.5, 88.5, 29.1, 27.5, 21.6, 13.3; Ms: m/z [M+] 423; Anal. Calc. for C27H21NO4: C,
76.58; H, 5.00; N, 3.31; Found: C, 76.54; H, 4.98; N, 3.23%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)){4-[(4-propylphenyl)ethynyl]phenyl}methanone (5d). Off white solid;
Yield: MW 81%, CH 3%; mp.: 79-81 oC; IR (KBr, νmax, cm-1): 3107 (νC-H aromatic), 2958 (νC-H aliphatic), 2208 (νCC
,
disubstituted), 1633 (νC=O), 1595 (νC=C aromatic), 1525 (νNO asymmetric), 1450 (νC=C aromatic), 1404 (δC-H),
2
1346 (νNO symmetric), 1263 (ν=C-O-C asymmetric) 1053 (ν=C-O-C symmetric), 1084 (δC-H aromatic), 833 (δCH p-
2
disubstituted aromatic); 1H NMR (400 MHz, DMSO-d6): δ 8.26 (t, J 5.6 Hz, 2H), 7.94 (d, J 8.8 Hz, 1H), 7.85 (d, J
8.0 Hz, 2H), 7.74 (d, J 8.4 Hz, 2H), 7.52 (d, J 8.0 Hz, 2H), 7.28 (d, J 8.0 Hz, 2H), 2.83 (t, J 7.6 Hz, 2H), 2.59 (t, J 7.6
Hz, 2H), 1.72-1.56 (m, 4H), 1.29-1.19 (m, 2H), 0.89 (t, J 7.2 Hz, 3H), 0.80 (t, J 7.4 Hz, 3H); 13C-NMR (101 MHz,
DMSO-d6): δ 189.5, 168.0, 155.9, 144.2, 143.8, 137.6, 131.6, 131.5, 129.2, 128.8, 127.2, 127.1, 120.6, 118.9,
117.0, 116.4, 112.3, 92.8, 88.0, 37.1, 29.1, 27.5, 23.8, 21.6, 13.6, 13.3; Ms: m/z [M+] 465; Anal. Calc. for
C30H27NO4: C, 77.40; H, 5.85; N, 3.01; Found: C, 77.36; H, 5.81; N, 2.97%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)){4-[((4-fluorophenyl)ethynyl]phenyl}methanone (5e). White solid; Yield:
o
MW 85%, CH 3%; mp.: 69-71 C; IR (KBr, νmax, cm-1): 3091 (νC=C aromatic), 2951 (νC-H aliphatic), 2218 (νCC
,
disubstituted), 1639 (νC=O), 1593 (νC=C aromatic), 1516 (νNO asymmetric), 1450 (νC=C aromatic), 1402 (δC-H
2
aromatic), 1346 (νNO symmetric), 1259 (ν=C-O-C asymmetric), 1051 (ν=C-O-C symmetric), 1078 (δC-H aromatic), 972
2
1
(νC-F), 848 (δCH p-disubstituted aromatic); H NMR (400 MHz, DMSO-d6): δ 8.27 (d, J 8.8 Hz, 2H), 7.94 (d, J 8.8
Hz, 1H), 7.86 (d, J 8.0 Hz, 2H), 7.75 (d, J 7.6 Hz, 2H), 7.69 (t, J 6.4 Hz, 2H), 7.31 (t, J 8.4 Hz, 2H), 2.83 (t, J 7.0 Hz,
2H), 1.68 (t, J 7.0 Hz, 2H), 1.25 (qt, J 7.2, 14.4 Hz, 2H), 0.81 (t, J 7.2 Hz, 3H); 13C-NMR (101 MHz, DMSO-d6): δ
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189.5, 168.1, 163.6, 161.1, 155.9, 144.2, 137.8, 134.0, 133.9, 131.7, 129.2, 127.1, 126.8, 120.6, 118.1, 118.1,
117.0, 116.4, 116.2, 116.0, 112.3, 91.5, 88.2, 29.1, 27.5, 21.6, 13.3; MS: m/z [M+] 441; Anal. Calc. for
C27H20FNO4: C, 73.46; H, 4.57; N, 3.17; Found: C, 73.40; H, 4.52; N, 3.16%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)[4-(cyclopropylethynyl)phenyl]methanone (5f). Yellow liquid; Yield: MW
o
1
91%, CH 6%; bp.: 228-230 C; H NMR (400 MHz, DMSO-d6): δ 8.24 (dd, J 2.4, 8.0 Hz, 2H), 7.91 (dd, J 2.4, 7.6
Hz, 1H), 7.75 (dd, J 1.6, 6.8 Hz, 2H), 7.54 (dd, J 2.0, 6.8 Hz, 2H), 2.79 (t, J 7.6 Hz, 2H), 1.69-1.57 (m, 3H), 1.27-
1.17 (m, 3H), 0.96-0.915 (m, 2H), 0.86-0.80 (m, 5H); 13C-NMR (101 MHz, DMSO-d6): δ 189.5, 168.0, 156.0,
144.3, 137.0, 131.7, 129.2, 128.3, 127.2, 120.7, 117.0, 116.5, 112.4, 98.1, 75.2, 29.3, 27.6, 21.8, 13.5, 8.8; Ms:
m/z [M+] 387; Anal. Calc. for C24H21NO4: C, 74.40; H, 5.46; N, 3.62; Found: C, 74.36; H, 5.41; N, 3.59%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)[4-(cyclopentylethynyl)phenyl]methanone (5g). Yellow liquid; Yield: MW
90%, CH 7%; bp.: 224-226 oC; 1H NMR (400 MHz, DMSO-d6): δ 8.24 (d, J 2.4 Hz, 1H), 8.22 (d, = 2.4 Hz, 1H), 7.90
(d, J 10.0 Hz, 1H), 7.75 (d, J 8.4 Hz, 2H), 2.54 (d, J 8.0 Hz, 2H), 2.92-2.77 (m, 3H), 2.01-1.96 (m, 2H), 1.74-1.55
(m, 8H), 1.24-1.19 (m, 2H), 0.78 (t, J 7.4 Hz, 3H) ; 13C-NMR (101 MHz, DMSO-d6): δ 189.4, 167.8, 155.9, 144.1,
137.0, 131.5, 129.0, 128.2, 127.1, 120.5, 116.9, 116.4, 112.2, 98.6, 79.5, 72.6, 33.3, 33.1, 30.1, 29.6, 27.5, 24.6,
24.5, 24.5, 22.9, 21.6, 13.3; MS: m/z [M+] 415; Anal. Calc. for C26H25NO4: C, 75.16; H, 6.07; N, 3.37; Found: C,
75.11; H, 6.01; N, 3.34%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)[4-(cyclohexylethynyl)phenyl]methanone (5h). Yellow liquid; Yield: MW
o
87%, CH 5%; bp.: 231-233 C; IR (KBr, νmax, cm-1): 3103 (νC-H aromatic), 2928 (νC-H aliphatic), 2224 (νCC
disubstituted), 1645 (νC=O), 1599 (νC=C aromatic), 1531 (νNO asymmetric), 1448 (νC=C aromatic), 1402 (δC-H),
2
1
1344 (νNO symmetric), 1251 (ν=C-O-C asymmetric), 1053 (ν=C-O-C symmetric), 1082 (δC-H aromatic); H NMR (400
2
MHz, DMSO-d6): δ 8.27-8.25 (m, 2H), 7.94 (d, J 10.0 Hz, 1H), 7.78 (d, J 8.4 Hz, 2H), 7.57 (d, J 8.4 Hz, 2H), 2.81 (t,
J 7.6 Hz, 2H), 2.70 (t, J 3.6 Hz, 1H), 1.86 (t, J 4.8 Hz, 2H), 1.70-1.63 (m, 4H), 1.54-1.47 (m, 4H), 1.40-1.33 (m,
4H), 1.28-1.20 (m, 2H), 0.80 (t, J 7.4 Hz, 3H); MS: m/z [M+] 429; Anal. Calc. for C27H27NO4: C, 75.50; H, 6.34; N,
3.26; Found: C, 75.43; H, 6.28; N, 3.22%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)[4-(hept-1-yn-1-yl)phenyl)]methanone (5i). White liquid; Yield: MW 93%,
CH 8%; bp.: 216-218 oC; 1H NMR (400 MHz, DMSO-d6): δ 8.25 (dd, J 2.4, 6.0 Hz, 2H), 7.93 (dd, J 3.6, 6.0 Hz, 1H),
7.78 (d, J 8.0 Hz, 2H), 7.57 (d, J 8.0 Hz, 2H), 2.80 (t, J 7.4 Hz, 2H), 2.48 (t, J 7.0 Hz, 2H), 1.71-1.63 (m, 2H), 1.61-
1.54 (m, 2H), 1.45-1.31 (m, 4H), 1.29-1.19 (m, 3H), 0.90 (t, J 7.0 Hz, 3H), 0.80 (t, J 7.4 Hz, 3H); 13C-NMR (101
MHz, DMSO-d6): δ 189.4, 167.9, 155.9, 144.2, 137.1, 131.5, 129.1, 128.1, 127.1, 120.6, 116.90, 116.4, 112.2,
94.7, 80.0, 30.5, 29.1, 27.7, 27.5, 21.6, 18.7, 13.8, 13.3; MS: m/z [M+] 417; Anal. Calc. for C26H27NO4: C, 74.80;
H, 6.52; N, 3.35; Found: C, 74.73; H, 6.52; N, 3.31%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)){4-[(4-ethylphenyl)ethynyl)]phenyl}methanone (5j). Yellow solid; Yield:
o
MW 81%, CH 8%; mp.: 60-62 C; IR (KBr, νmax, cm-1): 3101 (νC-H aromatic), 2922 (νC-H aliphatic), 2212 (νCC
,
disubstituted), 1653 (νC=O), 1597 (νC=C aromatic), 1531 (νNO asymmetric), 1450 (νC=C aromatic), 1404 (δC-H),
2
1
1342 (νNO symmetric), 1253 (ν=C-O-C asymmetric), 1055 (ν=C-O-C symmetric), 1080 (δC-H aromatic); H NMR (400
2
MHz, DMSO-d6): δ 8.28 (s, 1H), 8.25 (d, J 2.0 Hz, 1H), 7.93 (d, J 8.4 Hz, 1H), 7.85 (d, J 8.0 Hz, 2H), 7.74 (t, J 7.6
Hz, 2H), 7.52 (d, J 8.0 Hz, 1H), 7.29 (t, J 9.4 Hz, 2H), 2.82 (t, J 7.6 Hz, 2H), 2.65 (qt, J 7.6, 22.8 Hz, 2H), 1.71-1.64
(m, 2H), 1.28-1.17 (m, 5H), 0.80 (t, J 7.4 Hz, 3H); 13C-NMR (101 MHz, DMSO-d6): δ 189.5, 168.0, 155.9, 145.4,
137.6, 131.6, 129.2, 128.3, 127.2, 127.1, 120.6, 118.9, 116.9, 116.4, 112.3, 92.8, 88.0, 29.1, 28.1, 27.5, 21.6,
15.2, 13.3; MS: m/z [M+] 451; Anal. Calc. for C29H25NO4: C, 77.14; H, 5.58; N, 3.10; Found: C, 77.10; H, 5.54; N,
3.06%.
(2-Butyl-5-nitrobenzo[b]furan-3-yl)(4-ethynylphenyl)methanone (5k). off-white solid; Yield: MW 94%, CH
o
10%; mp.: 82-84 C; IR (KBr, νmax, cm-1): 3255 (νC-H), 3107 (νC-H aromatic), 2953 (νC-H aliphatic), 2158 (νCC
,
monosubstituted), 1639 (νC=O), 1564 (νC=C aromatic), 1523 (νNO asymmetric), 1450 (νC=C aromatic), 1346 (νNO
2
2
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1
), 1249 (ν=C-O-C asymmetric), 1055 (ν=C-O-C symmetric), 1082 (δC-H aromatic); H NMR (400 MHz,
symmetric
CDCl3): δ 8.13 (d, J 2.0 Hz, 1H), 8.01 (dd, J 2.4, 9.2 Hz, 1H), 7.54 (dd, J 1.6, 6.4 Hz, 2H), 7.38 (dd, J 2.0, 6.8 Hz,
3H), 2.66 (t, J 7.6 Hz, 2H), 1.57-1.49 (m, 2H), 1.16-1.02 (m, 3H), 0.67 (t, J 7.2 Hz, 3H); Ms: m/z [M+] 347; Anal.
Calc. for C21H17NO4: C, 72.61; H, 4.93; N, 4.03; Found: C, 72.55; H, 4.88; N, 3.99%.
Acknowledgements
The authors are thankful to the Department of Chemistry, Saurashtra University, Rajkot for providing the
laboratory facilities and Centre of Excellence (CoE), NFDD Complex, Rajkot for providing the spectral data.
Supplementary Material
1
Copies of Mass, IR, H NMR, 13C NMR and LC-MS spectra of synthesized compounds are available in the
Supplementary Material.
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