Efficient synthesis of isoquinolines and pyridines via copper(i)-catalyzed multi-component reaction

Article abstract of DOI:10.1039/c3ra46722h

A wide range of 3-substituted isoquinolines, steroidal pyridines, 5,6-dihydrobenzo[f]isoquinolines and 1,6-naphthyridine were synthesized in good yield via a ligand-free copper-catalyzed three-component reaction of β-halovinyl/aryl aldehyde, aromatic/alip

Full text of DOI:10.1039/c3ra46722h

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Efficient synthesis of isoquinolines and pyridines via
copper(I)-catalyzed multi-component reaction†
Cite this: RSC Adv., 2014, 4, 14013
*
*
Kommuri Shekarrao, Partha Pratim Kaishap, Sanjib Gogoi and Romesh C. Boruah
A wide range of 3-substituted isoquinolines, steroidal pyridines, 5,6-dihydrobenzo[f]isoquinolines and
1,6-naphthyridine were synthesized in good yield via a ligand-free copper-catalyzed three-component
reaction of b-halovinyl/aryl aldehyde, aromatic/aliphatic terminal alkyne and tert-butylamine/
benzamidine in DMF under microwave irradiation. A catalyst-free reaction of ortho-alkynyl aryl/vinyl
aldehydes with benzamidine under microwave irradiation also provided the 3-substituted isoquinoline
and substituted pyridine derivatives in excellent yield.
Received 15th November 2013
Accepted 31st January 2014
DOI: 10.1039/c3ra46722h
www.rsc.org/advances
synthesis of tert-butylimines from b-halovinyl aldehydes, fol-
lowed by coupling reaction of imine intermediates with alkynes
Introduction
and then cyclization of the resultant ortho-alkynyl aryl/vinyl
aldehydes in presence of other catalysts (typically CuI),7a–f long
reaction time, and low yield of the annulated products with
terminal mono-substituted acetylenes.7a Moreover, transition
metal complexes used as the catalytic systems are inadequate
for large-scale reaction owing to the high cost of these metal
complexes. From a synthetic point of view, it is essential for a
chemist to develop an improved and facile procedure to
synthesize these important heterocycles using a less expensive
and more sustainable catalyst. Our interests in the synthesis of
biologically important heterocycles have encouraged us to re-
investigate a catalytic synthesis version of these important
N-heterocycles.9 Herein, we wish to report a microwave-assisted
and CuI-catalyzed three-component reaction of b-halovinyl
aldehydes, terminal alkynes and tert-butylamine/benzamidine
under ligand-free conditions for the synthesis of nitrogen
heterocycles. This efficient synthesis of nitrogen heterocycles
A reaction where one catalyst promotes more than one chemical
transformation is always advantageous because this reaction
eliminates the isolation of intermediates as well as forming
several bonds from readily available starting materials.1 On the
other hand, multi-component reactions are recognized as
powerful tools for the synthesis of organic compounds, since
the products are formed in a single step and the diversity of the
products is maintained by simply varying the starting
materials.2
3-Aryl-substituted isoquinolines are of great pharmaceutical
importance due to their wide range of biological activities.3
They also constitute the building blocks of numerous biologi-
cally important natural products.4 Some of the biologically
active 3-arylisoquinoline derivatives are shown in Fig. 1.
Synthesis of other pyridine annulated molecules such as
steroidal pyridines,5a–f 5,6-dihydrobenzo[f]isoquinolines5g and
1,6-naphthyridine derivatives5h has received considerable
attention in the literature as a result of their biological and
pharmaceutical importance.
3-Arylisoquinolines are synthesized by Bischler–Napieralski
and Pictet–Spengler reactions which require either harsh
conditions or tedious reaction procedures.6 Pd-catalyzed
annulation processes are widely used to synthesize many
nitrogen heterocycles such as isoquinolines7 and 5,6-dihy-
drobenzo[f]isoquinolines.5g In addition to Pd, other transition
metals such as Ni,8a Zr8b and Ag8c are also used to synthesize
3-substituted isoquinoline derivatives. Although these methods
are useful for the synthesis of 3-arylisoquinolines and pyridine
derivatives, they have some disadvantages such as the stepwise
Medicinal Chemistry Division, CSIR-North East Institute of Science and Technology,
Jorhat 785006, India. E-mail: skgogoi1@gmail.com; rc_boruah@yahoo.co.in; Fax:
+913762370011; Tel: +91 3762372948
† Electronic supplementary information (ESI) available: Copies of 1H NMR, 13C
NMR spectra of 2a–y and MTT assay protocol. See DOI: 10.1039/c3ra46722h
Fig. 1 Selected biologically active 3-arylisoquinoline derivatives.
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Table 1 Effects of copper sources, solvents, amount of Cu(I) and
source of energy on the reaction of 2-bromobenzaldehyde, phenyl-
acetylene and tert-butylamine
was observed (entry 10, Table 1). We also explored the effect of
catalyst loading on the yield of the reaction. When the quantity
of CuI was reduced to 5 mol%, the yield decreased to 78% (entry
11, Table 1) under microwave irradiation. Increase of catalyst
loading to 15 mol% did not affect the yield of the reaction (entry
12, Table 1).
With the optimized reaction conditions in hand (entry 10,
Table 1), a series of terminal aliphatic and aromatic alkynes
were tested under this condition with 2-bromobenzaldehyde to
afford 3-substituted isoquinolines 2b–e in 75–84% yields (entry
2–5, Table 2). In addition to 2-bromobenzaldehyde 1a, we were
pleased to observe that 2-chloroaryl aldehydes such as 6-chlor-
obenzo[1,3]dioxole-5-carbaldehyde (1b) also worked well for
this reaction with the same catalyst loading to afford iso-
quinolines 2f–h in 71–84% yields (entry 6–8, Table 2). It was
interesting to note that these optimized reaction conditions
were also effective for annulations of b-bromovinyl aldehydes to
pyridine derivatives. For example, the annulations of steroidal
b-bromovinyl aldehyde 1c9b with different aryl and alkyl group-
substituted terminal alkynes under optimized reaction condi-
tions afforded the steroidal pyridines 2i–n in 70–82% yields
(entry 9–14, Table 2).
Entry Cu salt (mol%) Solvent
Thermal/MW Time Yielda (%)
1
2
3
4
5
6
7
8
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuBr (10)
CuCl (10)
Cu(OAc)2 (10)
Cu(OTf)2 (10)
—
DCE
DMF
120 ꢀ
120 ꢀ
120 ꢀ
C
C
C
C
C
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
27
61
25
40
56
44
<5
<5
0
Toluene
1,4-Dioxane 120 ꢀ
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
120 ꢀ
120 ꢀC
120 ꢀ
120 ꢀ
120 ꢀ
C
C
C
9
10
11
12
CuI (10)
CuI (5)
CuI (15)
720 W
720 W
720 W
4 min 92
4 min 78
4 min 91
a
Isolated yield.
Similarly, b-bromovinyl aldehydes such as 1-bromo-3,4-
dihydronaphthalene-2-carbaldehyde (1d)9b and 1-bromo-6-
methoxy-3,4-dihydronaphthalene-2-carbaldehyde (1e)9b reacted
with a range of aliphatic/aromatic terminal alkynes to afford
9,10-dihydrobenzo[f]isoquinolines 2o–s in 72–83% yields (entry
15–19, Table 2). In order to nd out the feasibility of the present
methodology for the preparation of the 1,6-naphthyridine
such as 3-substituted isoquinolines, steroidal pyridines,
5,6-dihydrobenzo[f]isoquinolines and 1,6-naphthyridine elimi-
nates the above-mentioned problems with Pd catalysts.
Results and discussion
Initial studies were performed by using 2-bromobenzaldehyde derivative, 2-chloro-5-(p-tolyl)pyridine-3-carbaldehyde (1f)9c was
1a, phenylacetylene and tert-butylamine as the model treated with phenylacetylene under similar reaction conditions
substrates, employing copper(I) iodide as the catalyst (Table 1) to afford the expected product 2t in 70% yield (entry 20, Table
and 1,2-dichloroethane (DCE) as the solvent under thermal 2). It was observed that aliphatic terminal alkynes afforded
conditions at 120 ꢀC. Gratifyingly, this reaction proceeded relatively low yields of the annulated products in comparison
smoothly in DCE to afford regioselectively the annulated with that of aromatic terminal alkynes. In all these cases, no
product 2a in 27% yield in 12DCEh (entry 1, Table 1). Further dimerized by-product of the terminal alkyne was observed.
investigation revealed that the solvent used played a signicant Moreover, good functional-group compatibility was demon-
role in this reaction. DMF was the most effective among the strated with aromatic alkynes substituted with methyl, methoxy
tested solvents and the yield of 2a was increased to 61% (entry 2, and uoro groups and all proved to be effective annulation
Table 1), while there was sharp decrease in the yield to 25% partners.
(entry 3, Table 1) and 40% (entry 4, Table 1), when toluene and
Recently, when we were trying to perform the synthesis of the
1,4-dioxane were used respectively. Several other copper sources eight-membered heterocycle 4 (Scheme 1) by the reaction of
were also examined (entry 5–8, Table 1) and CuI turned out to be equimolar amounts of 2-(phenylethynyl)benzaldehyde (3a),
the best among others in view of the yield of the annulated benzamidine hydrochloride and triethylamine under micro-
ꢀ
product. The use of Cu(II) salts provided only trace amounts of wave irradiation (720 W, 140 C, 14 bar), we obtained only the
the product 2a (entry 7–8, Table 1) and no product was formed isoquinoline derivative 2a (89%) and benzonitrile from the
in the absence of Cu(I) (entry 9,Table 1).
reaction mixture aer 5 min of reaction time. A literature search
At this stage of the investigation, we attempted rst to nd on similar cyclization reactions revealed various methods for
an efficient system for annulation of the b-bromophenyl alde- the regioselective cyclization reaction of ortho-arylalkynyl alde-
hyde and terminal alkyne under thermal conditions. Following hyde derivatives to isoquinolines. For example, (i) Gao and
this we were interested in looking for more attractive reaction Zhang developed an efficient Ag(I)-catalyzed regioselective
conditions in terms of time and reaction yield. Therefore, we cyclization reaction of ortho-alkynylaryl aldehyde oxime deriva-
examined the inuence of microwave (MW) irradiation on the tives to isoquinolines where benzaldehyde was formed as the
reaction of 1a, phenylacetylene and tert-butylamine in the side product (reaction (1), Scheme 2);10 (ii) Larock et al. reported
presence of 10 mol% CuI using the best solvent DMF. A the synthesis of isoquinolines from N-tert-butyl-2-(1-alkynyl)
substantial increase in the yield of 2a (92%) along with a arylaldimines in the presence of Lewis acid catalyst (Pd, Cu)
signicant reduction in the reaction time from 12 h to 4 min where isobutene was eliminated (reaction (2), Scheme 2);7a,b (iii)
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Table 2 CuI-catalyzed synthesis of pyridine-fused compoundsa
Entry
b-Halovinyl aldehyde
Alkyne
Productb (% Yield)
1
2
3
1a
1a
4
5
6
1a
1a
7
8
1b
1b
9
10
1c
1c
11
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Table 2 (Contd.)
Entry
b-Halovinyl aldehyde
Alkyne
Productb (% Yield)
12
1c
13
14
1c
1c
15
16
17
18
19
1d
1d
1e
20
a
Conditions: 10 mol% CuI, b-halovinyl aldehyde (1 mmol), alkyne (1.1 mmol) and tert-butylamine (2 mmol) in DMF (1 mL) was irradiated in a
b
closed vessel in a Synthos 3000 microwave reactor at 720 W (140 ꢀC and 14 bar) for 4 min. Refers to the amount of product isolated by
chromatography. c The reaction was performed for 8 min.
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the known ortho-arylalkynyl aldehydes (3b–h) which were
prepared using a known procedure.12 As shown in Table 3,
various substituted ortho-alkynyl aryl/vinyl aldehydes (3b–h)
were reacted with benzamidine hydrochloride in the presence
of triethylamine under microwave irradiation to afford
substituted isoquinolines 2a, 2c, 2e, 2u–w in 86–93% yield
(entry 1–6, Table 3) and pyridine derivatives 2x,y in 86–93% yield
(entry 7–8, Table 3). Encouraged by these results we were
interested to see the feasibility of the above copper-catalyzed
three-component reaction using benzamidine hydrochloride in
place of tert-butylamine as the source of nitrogen under
microwave energy. We were delighted to see that this three-
component reaction also worked well in the presence of ben-
zamidine hydrochloride even though the yields of the products
were less as compared to the above tert-butylamine reaction.
Thus, the three-component reaction of b-haloaryl aldehydes 1a,
1b, 1d with phenylacetylene and benzamidine hydrochloride
provided isoquinoline derivatives 2a (69%), 2v (74%) and 2o
(67%) respectively under microwave irradiation (720 W, 140 ꢀC,
14 bar, 8 min) in the presence of triethylamine (Scheme 3). We
also performed the multi-component reactions of 1a and ben-
zamidine hydrochloride with 4-uorophenylacetylene, n-pro-
pylacetylene and 4-methoxyphenylacetylene under the above
reaction conditions to afford compounds 2c (64%), 2e (57%)
and 2u (66%) respectively (Scheme 3).
Scheme 1 Catalyst-free synthesis of isoquinolines.
Based on our ndings and literature information,13 a plau-
sible mechanism for the tandem reaction is proposed as shown
in Scheme 4. The formation of a p-complex between the Cu(I)
ion and the triple bond in the presence of the base tert-buyl-
amine activates the triple bond towards deprotonation to form
copper(I) acetylide 5a. Subsequently, oxidative addition of this
copper(I) acetylide 5a with b-halovinyl aldehyde in the presence
of tert-butylamine generates probably copper(III) imine species
5b,13a(Scheme 29),d which on reductive elimination produces copper-
coordinated intermediate 5c. The intermediate 5c undergoes
6-endo-dig cyclization to provide regioselectively the iminium
intermediate 5d. Fragmentation of the tert-butyl group of 5d to
relieve the strain resulting from interaction of the tert-butyl
group with the substituent present in the ortho-position, fol-
lowed by protonation, leads to the formation of compound 2
with the liberation of Cu(I) catalyst.14 Furthermore, a possible
mechanism of cyclization of compound 3 in the presence of
benzamidine hydrochloride is shown in Scheme 5. Benzami-
dine hydrochloride forms imine 5e with aldehyde 3 in presence
of base triethylamine. The 6-endo-dig-cyclization of 5e and
subsequent C–N bond cleavage lead to the formation of
compound 2 and benzonitrile. The formation of benzonitrile
was proved by taking thin layer chromatography of the crude
Scheme 2 Synthesis of isoquinolines.
Ghavtadze et al. explored the silver nitrate-assisted cyclization
of N-{2-[alkynyl(hetero)aryl]methylene}indolin-1-amines to give
the pyridine derivatives where indole was liberated as a leaving
group (reaction (3), Scheme 2);11 (iv) Liang et al. studied the
synthesis of substituted isoquinolines using 2-alkynylbenzyl
azides as the starting material and Ag complex as the catalyst
(reaction (4), Scheme 2).8c Our catalyst-free, simple method of
cyclization of ortho-arylalkynyl aldehyde (3a) to the isoquinoline
derivative 2a using benzamidine (reaction (5), Scheme 2)
prompted us to study the cyclization reaction with some more of
Scheme 3 Multicomponent synthesis of 3-substituted isoquinolines and substituted pyridines.
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Table 3 Catalyst-free synthesis of 3-substituted isoquinolines and substituted pyridinesa
Entry
ortho-Alkynyl aryl/vinyl aldehydes
Product
Yieldb (%)
1
89
2
3
4
87
86
93
5
6
7
90
89
86
8
93
a
Conditions: ortho-alkynyl aryl/vinyl aldehydes (1 mmol), benzamidine hydrochloride (1.1 mmol) and triethylamine (1.1 mmol) was irradiated in a
b
closed vessel in a Synthos 3000 microwave reactor at 720 W (140 ꢀC and 14 bar) for 5 min. Refers to the amount of product isolated by
chromatography.
reaction mixture and conrmed by the presence of the molec- cancer cell line (compounds 2a–y, IC50 P 100 mM, doxorubicin
ular ion peak [M+] at m/z 103 in GC-MS.
IC50 ¼ 9.00 ꢁ 0.721 mM).
Because of the anticancer activity shown by different iso-
quinoline derivatives and heterosteroids, all the compounds
were screened in vitro for cytotoxic activities against the cervical
HeLa cancer cell line and prostate DU 205 cancer cell line using
the MTT-microcultured tetrazolium assay15 and drug doxoru-
bicin as a positive control. Unfortunately, none of the tested
compounds could show promising cytotoxic activity against the
cervical HeLa cancer cell line (compounds 2a–y, IC50 P 100 mM,
doxorubicin IC50 ¼ 9.76 ꢁ 0.1141 mM) and prostate DU 205
Conclusions
In conclusion, we have demonstrated very efficient multi-
component reactions for the synthesis of biologically important
3-substituted isoquinolines, steroid-fused pyridines, 5,6-dihy-
drobenzo[f]isoquinolines and 1,6-naphthyridine. These copper-
catalyzed microwave-assisted annulation reactions are much
more efficient than the known transition metal-catalyzed
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performed on pre-coated silica gel plates (Merck). Column
chromatography was performed on silica gel (100–200 mesh,
Merck). All MW reactions were carried out in a Synthos 3000
(Anton Paar) microwave reactor.
General procedure for the multi-component synthesis of
compounds 2a–t using tert-butylamine. A mixture of halo
aldehyde (1 mmol), 10 mol% CuI, terminal alkyne (1.1 mmol)
and tert-butylamine (2 mmol) in DMF (1 mL) was irradiated in
a closed vessel in a Synthos 3000 microwave reactor at 720 W
(140 ꢀC and 14 bar) for 4–8 min. Aer completion of the
reaction, as indicated by TLC, the reaction mixture was treated
with water (40 mL) and then extracted with ethyl acetate (50
mL). The organic portion was washed with water, dried over
anhydrous sodium sulfate and the solvent was removed to
obtain a crude product which on silica gel column chro-
matographic purication using EtOAc/hexane (1 : 4) as eluent
afforded compounds 2a–t.
Scheme 4 Plausible mechanism of Cu(I)-mediated formation of 2.
3-Phenylisoquinoline.7c (2a) Yellow gum, yield: 92% (188 mg).
1H NMR (CDCl3, 300 MHz) d 7.42 (t, J ¼ 7.2 Hz, 1H), 7.52 (t, J ¼
7.2 Hz, 2H), 7.60 (t, J ¼ 7.9 Hz, 1H), 7.69 (t, J ¼ 7.1 Hz, 1H), 7.89
(d, J ¼ 8.3 Hz, 1H), 8.00 (d, J ¼ 8.1 Hz, 1H), 8.08 (s, 1H), 8.12 (d, J
¼ 7.3 Hz, 2H), 9.35 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 116.6,
126.9, 127.0, 127.1, 127.6, 127.8, 128.5, 128.7, 128.8, 130.2,
130.5, 136.7, 139.6, 151.3, 152.4. IR (CHCl3, cmꢂ1): 3058, 2971,
1790, 1626, 1592, 1492, 1448, 1205, 977, 764. MS (EI, m/z): 205
[M+]. Anal. calcd for C15H11N: C, 87.77; H, 5.40; N, 6.82. Found:
C, 87.59; H, 5.49; N, 6.67%.
3-(p-Tolyl)isoquinoline (2b). Brown solid, yield: 84% (184 mg).
M.p. 71–72 ꢀC. 1H NMR (CDCl3, 300 MHz) d 2.44 (s, 3H), 7.33 (d,
J ¼ 8.1 Hz, 2H), 7.52 (t, J ¼ 7.8 Hz, 1H), 7.63 (t, J ¼ 7.8 Hz, 1H),
7.79 (d, J ¼ 8.4 Hz, 1H), 7.93 (d, J ¼ 8.1 Hz, 1H), 8.00 (s, 1H), 8.07
(d, J ¼ 7.8 Hz, 2H), 9.33 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 21.4,
116.0, 126.9, 127.6, 127.63, 129.6, 130.5, 136.7, 136.8, 138.5,
151.2, 152.3. IR (CHCl3, cmꢂ1): 1626, 1589, 1516, 1447, 823, 751.
MS (EI, m/z): 219.1 [M+]. Anal. calcd for C16H13N: C, 87.64; H,
5.98; N, 6.39. Found: C, 87.69; H, 5.99; N, 6.57%.
Scheme 5 Plausible mechanism of catalyst-free formation of 2.
reactions in terms of the rate of reaction, cost of catalyst and
steps of the reactions. A wide range of terminal alkynes undergo
this reaction with b-halovinyl/aryl aldehydes and tert-butyl-
amine/benzamidine to provide good to excellent yield of prod-
3-(4-Fluorophenyl)isoquinoline (2c). Yellow solid, yield: 76%
1
ꢀ
(170 mg). M.p. 124–125 C. H NMR (CDCl3, 300 MHz) d 7.13–
7.22 (m, 2H), 7.53 (t, J ¼ 6.9 Hz, 1H), 7.65 (t, J ¼ 6.9 Hz, 1H), 7.78
(d, J ¼ 8.1 Hz, 1H), 7.92 (d, J ¼ 6.6 Hz, 1H), 7.93 (s, 1H), 8.12–
8.02 (m, 2H), 9.28 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 115.5,
115.8, 116.2, 126.8, 127.1, 127.5, 128.7, 128.8, 130.6, 135.7,
136.6, 150.2, 152.4, 164.0 (d, JC–F ¼ 246 Hz). IR (CHCl3, cmꢂ1):
1625, 1600, 1581, 1512, 836. MS (EI, m/z): 223 [M+]. Anal. calcd
for C15H10FN: C, 80.70; H, 4.51; N, 6.27. Found: C, 80.82; H,
4.60; N, 6.42%.
ucts. Moreover,
a catalyst-free synthesis of biologically
important 3-substituted isoquinoline and substituted pyridine
derivatives was developed using ortho-alkynyl aryl/vinyl alde-
hydes, benzamidine hydrochloride and triethylamine as the
starting materials under microwave irradiation.
Experimental
General methods
3-(6-Methoxynaphthalen-2-yl)isoquinoline (2d). Light yellow
1
ꢀ
solid, yield: 79% (225 mg). M.p. 171–172 C. H NMR (CDCl3,
Melting points were measured with a Buchi B-540 melting point 300 MHz) d 3.95 (s, 3H), 7.17–7.26 (m, 2H), 7.58 (t, J ¼ 7.2 Hz,
apparatus and are uncorrected. IR spectra were recorded using 1H), 7.70 (t, J ¼ 6.9 Hz, 1H), 7.83–7.91 (m, 3H), 8.00 (d, J ¼
an Elmer FT-IR-2000 spectrometer using KBr pellets or as a thin 8.1 Hz, 1H), 8.18–8.23 (m, 2H), 8.59 (s, 1H), 9.37 (s, 1H). 13C
lm using chloroform. NMR spectra were recorded using an NMR (CDCl3, 75 MHz) d 55.4, 105.6, 116.4, 119.2, 125.2,
Avance DPX 300 MHz FT-NMR spectrometer using tetrame- 126.1, 126.9, 127.0, 127.3, 127.6, 129.2, 130.3, 130.6, 134.7,
thylsilane (TMS) as an internal standard. Mass spectra were 136.8, 151.2, 152.5, 158.1. IR (CHCl3, cmꢂ1): 1621, 1260, 1024,
recorded on a Trace DSQ GCMS instrument. All the commer- 853, 773, 743. MS (EI, m/z): 285.1 [M+]. Anal. calcd for
cially available regents were used as received. All experiments
C20H15NO: C, 84.19; H, 5.30; N, 4.91. Found: C, 84.27; H,
were monitored by thin layer chromatography (TLC). TLC was 5.36; N 4.76%.
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3-Propylisoquinoline (2e). Yellow gum, yield: 75% (128 mg). 1H
NMR (CDCl3, 300 MHz) d 1.00 (t, J ¼ 7.2 Hz, 3H), 1.80 (hextet, J ¼
7.2 Hz, 2H), 2.91 (t, J ¼ 7.7 Hz, 2H), 7.44 (s, 1H), 7.50 (t, J ¼ 7.7
Hz, 1H), 7.62 (t, J ¼ 7.8 Hz, 1H), 7.73 (d, J ¼ 8.2 Hz, 1H), 7.90 (d, J
¼ 8.0 Hz, 1H), 9.19 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 13.9,
23.2, 40.1, 118.1, 126.1, 126.3, 127.1, 127.5, 130.2, 136.5, 152.0,
155.5. IR (CHCl3, cmꢂ1): 2960, 2932, 2871, 1630, 1592, 1456,
751. MS (EI, m/z): 171 [M+]. Anal. calcd for C12H13N: C, 84.17; H,
7.65; N, 8.18. Found: C, 84.03; H, 7.55; N, 8.29%.
57.2, 73.8, 113.4, 122.1, 126.8, 129.4, 137.0, 137.2, 138.4, 140.0,
145.4, 155.9, 164.0, 170.6. IR (CHCl3, cmꢂ1): 1729, 1374, 1254,
1034, 823, 753. MS (EI, m/z): 395.2 [M+ ꢂ 60]. Anal. calcd for
C
31H37NO2: C, 81.72; H, 8.19; N, 3.07. Found: C, 81.75; H, 8.28;
N, 3.27%.
3b-Acetoxy-60-[p-uorophenyl]-5,16-androstadieno[16,17-c]pyri-
1
ꢀ
dine (2k). Red solid, yield: 77% (354 mg). M.p. 176–177 C. H
NMR (CDCl3, 300 MHz) d 1.0 (s, 3H), 1.11 (s, 3H), 2.05 (s, 3H),
0.89–2.36 (m, 15H), 2.59 (t, J ¼ 11.2 Hz, 1H), 2.78 (dd, J ¼ 14.6
Hz and 5.0 Hz, 1H), 4.49–4.77 (m, 1H), 5.44 (d, J ¼ 7.5 Hz, 1H),
7.14 (t, J ¼ 8.4 Hz, 2H), 7.43 (s, 1H), 7.93 (t, J ¼ 6.0 Hz, 2H), 8.50
(s, 1H). 13C NMR (CDCl3, 75 MHz) d 18.6, 19.4, 20.6, 21.5, 27.7,
29.6, 29.7, 29.8, 30.8, 31.6, 34.1, 36.85, 36.9, 38.1, 45.7, 50.3,
57.2, 73.8, 115.5, 115.7, 122.1, 128.8, 128.9, 140.0, 163.1 (d, JC–F
¼ 223 Hz), 170.6. IR (CHCl3, cmꢂ1): 2927, 1722, 1245, 1033. MS
(EI, m/z): 399.2 [M+ ꢂ 60]. Anal. calcd for C30H34FNO2: C, 78.40;
H, 7.46; N, 3.05. Found: C, 78.51; H, 7.29; N, 3.13%.
7-(p-Methoxyphenyl)-[1,3]-dioxolo[4,5-g]isoquinoline (2f). Red
1
ꢀ
solid, yield: 84% (234 mg). M.p. 159–160 C. H NMR (CDCl3,
300 MHz) d 3.86 (s, 3H), 6.07 (s, 2H), 7.01 (d, J ¼ 7.8 Hz, 2H), 7.06
(s, 1H), 7.16 (s, 1H), 7.79 (s, 1H), 7.99 (d, J ¼ 7.8 Hz, 2H), 9.02 (s,
1H). 13C NMR (CDCl3, 75 MHz) d 55.4, 101.6, 102.6, 103.1, 114.1,
115.5, 124.6, 128.0, 132.2, 135.2, 148.1, 149.9, 150.2, 151.1,
159.9. IR (CHCl3, cmꢂ1): 1598, 1455, 1225, 1026. MS (EI, m/z):
279 [M+]. Anal. calcd for C17H13NO3: C, 73.11; H, 4.69; N, 5.02.
Found: C, 73.24; H, 4.80; N, 5.25%.
3b-Acetoxy-60-propyl-5,16-androstadieno[16,17-c]pyridine (2l).
Yellow solid, yield: 70% (285 mg). M.p. 161–162 ꢀC. 1H NMR
(CDCl3, 300 MHz) d 0.95 (s, 3H), 1.10 (s, 3H), 2.04 (s, 3H), 0.90–
2.60 (m, 20H), 2.71–2.80 (m, 4H) 4.55–4.68 (m, 1H), 5.42 (d, J ¼
5.3 Hz, 1H), 6.93 (s, 1H), 8.35 (s, 1H). 13C NMR (CDCl3, 75 MHz)
d 13.9, 18.6, 19.3, 20.6, 21.4, 23.4, 27.7, 29.7, 30.8, 31.6, 34.1,
36.8, 36.9, 38.1, 39.9, 45.5, 50.4, 57.1, 73.7, 115.8, 122.0, 136.1,
140.0, 143.9, 159.8, 164.6, 170.5. IR (CHCl3, cmꢂ1) 2928, 2853,
1733, 1244, 1033. MS (EI, m/z): 347.3 [M+ ꢂ 60]. Anal. calcd for
7-(p-Fluorophenyl)-[1,3]-dioxolo[4,5-g]isoquinoline (2g). Brown
1
ꢀ
solid, yield: 78% (208 mg). M.p. 161–162 C. H NMR (CDCl3,
300 MHz) d 6.11 (s, 2H), 7.09–7.21 (m, 4H), 7.84 (s, 1H), 8.00–
8.07 (m, 2H), 9.05 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 101.7,
102.7, 103.1, 115.5, 115.8, 116.1, 124.9, 128.4, 135.1, 135.8,
148.4, 149.6, 150.1, 151.2, 163.1 (d, JC–F ¼ 246 Hz). IR (CHCl3,
cmꢂ1): 1602, 1463, 1233, 956, 843. MS (EI, m/z): 267.0 [M+]. Anal.
calcd for C16H10FNO2: C, 71.91; H, 3.77; N, 5.24. Found: C,
71.98; H, 3.83; N, 5.45%.
C
27H37NO2: C, 79.56; H, 9.15; N, 3.44. Found: C, 79.58; H, 9.20;
N, 3.30%.
3b-Acetoxy-60-butyl-5,16-androstadieno[16,17-c]pyridine (2m).
7-Butyl-[1,3]-dioxolo[4,5-g]isoquinoline (2h). Brown solid,
yield: 71% (163 mg). M.p. 68–69 ꢀC. 1H NMR (CDCl3, 300 MHz) d
0.91 (t, J ¼ 7.2 Hz, 3H), 1.25–1.41 (m, 2H), 1.72 (pentate, J ¼ 7.8
Hz, 2H), 2.83 (t, J ¼ 6.6 Hz, 2H), 6.03 (s, 2H), 6.95 (s, 1H), 7.11 (s,
1H), 7.27 (s, 1H), 8.88 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 14.0,
22.5, 32.2, 37.5, 101.4, 102.0, 103.0, 117.9, 124.1, 135.0, 147.8,
149.6, 151.0, 154.7. IR (CHCl3, cmꢂ1): 1605, 1483, 1457, 1237,
1037, 940. MS (EI, m/z): 229.1 [M+]. Anal. calcd for C14H15NO2: C,
73.34; H, 6.59; N, 6.11. Found: C, 73.37; H, 6.71; N, 6.39%.
3b-Acetoxy-60-phenyl-5,16-androstadieno[16,17-c]pyridine (2i).
Yellow solid, yield: 82% (362 mg). M.p. 185–186 ꢀC. 1H NMR
(CDCl3, 300 MHz) d 0.94 (s, 3H), 1.04 (s, 3H), 0.79–2.4 (m, 14H),
1.97 (s, 3H), 2.40–2.58 (m, 1H), 2.64–2.82 (m, 1H), 4.47–4.64 (m,
1H), 5.36 (d, J ¼ 4.6 Hz, 1H), 7.22 (s, 1H), 7.25–7.50 (m, 4H), 7.88
(d, J ¼ 7.3 Hz, 2H), 8.46 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 18.7,
19.4, 20.6, 21.5, 27.7, 29.8, 30.8, 31.6, 34.2, 36.9, 38.1, 45.7, 50.4,
57.2, 73.8, 113.8, 122.1, 127.0, 128.7, 137.4, 139.6, 140.0, 145.2,
155.8, 164.5, 170.6. IR (CHCl3, cmꢂ1) 2926, 2854, 1731, 1657,
1243, 1031. MS (EI, m/z): 381.2 [M+ ꢂ 60]. Anal. calcd for
Yellow solid, yield: 69% (291 mg). M.p. 168 ꢀC. 1H NMR (CDCl3,
300 MHz) d 0.94 (s, 3H), 1.10 (s, 3H), 2.04 (s, 3H), 0.90–2.62 (m,
22H), 2.71–2.80 (m, 4H) 4.55–4.68 (m, 1H), 5.43 (d, J ¼ 4.5 Hz,
1H), 6.91 (s, 1H), 8.34 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 14.0,
18.6, 19.3, 20.6, 21.4, 22.7, 28.8, 29.7, 30.8, 31.6, 32.4, 34.1, 36.8,
38.1, 45.4, 50.4, 57.2, 73.8, 115.5, 122.1, 135.8, 140.0, 144.8,
160.5, 163.7, 170.5. IR (CHCl3, cmꢂ1): 2955, 2934, 2855, 1733,
1245, 1033, 755. MS (EI, m/z): 361.2 [M+ ꢂ 60]. Anal. calcd for
C
28H39NO2: C, 79.76; H, 9.32; N, 3.32. Found: C, 79.78; H, 9.37;
N, 3.42%.
3b-Acetoxy-60-ethoxycarbonyl-5,16-androstadieno[16,17-c]pyri-
dine (2n). Yellow solid, yield: 74% (324 mg). M.p. 129 ꢀC. 1H
NMR (CDCl3, 300 MHz) d 0.98 (s, 3H), 1.10 (s, 3H), 1.45 (t, J ¼ 7.4
Hz, 3H), 2.05 (s, 3H), 1.11–3.00 (m, 17H), 4.48 (q, J ¼ 7.1 Hz, 2H),
4.50–4.65 (m, 1H), 5.43 (d, J ¼ 4.6 Hz, 1H), 7.90 (s, 1H), 8.59 (s,
1H). 13C NMR (CDCl3, 75 MHz) d 14.4, 18.5, 19.3, 20.5, 21.4,
27.7, 30.2, 30.8, 31.5, 34.0, 36.9, 38.1, 45.7, 50.3, 57.1, 61.9, 73.7,
118.2, 121.9, 140.0, 142.8, 145.9, 146.9, 164.4, 170.6. IR (CHCl3,
cmꢂ1) 2850, 1728, 1374, 1246, 1031. MS (EI, m/z): 377.2
[M+ ꢂ 60]. Anal. calcd for C27H35NO4: C, 74.11; H, 8.06; N, 3.20.
Found: C, 74.25; H, 8.14; N, 3.39%.
C
30H35NO2: C, 81.59; H, 7.99; N, 3.17. Found: C, 81.49; H, 7.96;
N, 3.24%.
3b-Acetoxy-60-(p-tolyl)-5,16-androstadieno[16,17-c]pyridine (2j).
Black solid, yield: 79% (360 mg). M.p. 206–208 ꢀC. 1H NMR
(CDCl3, 300 MHz) d 0.97 (s, 3H), 1.09 (s, 3H), 2.05 (s, 3H), 0.90–
2.42 (m, 15H), 2.40 (s, 3H), 2.55 (t, J ¼ 11.4 Hz, 1H), 2.80 (dd, J ¼
14.7 Hz and 5.1 Hz, 1H), 4.49–4.78 (m, 1H), 5.42 (d, J ¼ 4.6 Hz,
1H), 7.26 (d, J ¼ 7.8 Hz, 2H), 7.45 (s, 1H), 7.86 (d, J ¼ 8.4 Hz, 2H),
8.50 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 19.4, 20.6, 21.3, 21.5,
22.7, 27.7, 29.7, 30.8, 31.6, 34.1, 36.85, 36.9, 38.1, 45.5, 50.4,
3-Phenyl-9,10-dihydrobenzo[f]isoquinoline (2o). Yellow gum,
yield: 83% (213 mg). 1H NMR (CDCl3, 300 MHz) d 2.86–3.05 (m,
4H), 7.02–7.52 (m, 6H), 7.82–8.04 (m, 4H), 8.56 (s, 1H). 13C NMR
(CDCl3, 75 MHz) d 25.2, 28.5, 114.8, 124.3, 126.9, 127.3, 128.7,
128.8, 129.6, 130.5, 132.1, 138.3, 139.7, 142.7, 148.8, 156.6. IR
(CHCl3, cmꢂ1): 2926, 2850, 1599, 1475, 1448, 771, 743. MS (EI,
14020 | RSC Adv., 2014, 4, 14013–14023
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m/z): 257.1 [M+]. Anal. calcd for C19H15N: C, 88.68; H, 5.88; N, indicated by TLC, the reaction mixture was treated with water
5.44. Found: C, 88.76; H, 5.64; N, 5.59%. (40 mL) and then extracted with ethyl acetate (40 mL). The
3-Propyl-9,10-dihydrobenzo[f]isoquinoline (2p). Yellow gum, organic portion was washed with water, dried over anhydrous
yield: 75% (167 mg). 1H NMR (CDCl3, 300 MHz) d 0.93 (t, J ¼ 7.4 sodium sulfate and the solvent was removed to obtain a crude
Hz, 3H), 1.74 (hextet, J ¼ 7.3 Hz, 2H), 2.71–2.90 (m, 6H), 7.10– product which on silica gel column chromatographic puri-
7.32 (m, 3H), 7.40 (s, 1H), 7.72 (t, J ¼ 3.6 Hz, 1H), 8.32 (s, 1H). cation using EtOAc/hexane (1 : 4) as eluent afforded
13C NMR (CDCl3, 75 MHz) d 13.9, 23.3, 25.1, 28.5, 40.0, 116.7, compounds 2a, 2c, 2e, 2u–y. The spectral data of compounds
124.3, 127.2, 128.6, 129.2, 129.5, 132.0, 138.4, 142.6, 147.7, 2a (89%, 182 mg), 2c (87%, 194 mg) and 2e (86%, 147 mg) are
160.6. IR (CHCl3, cmꢂ1): 2959, 2933, 2871, 1603, 1544, 1483, similar to those mentioned above.
772. MS (EI, m/z): 223 [M+]. Anal. calcd for C16H17N: C, 86.05; H,
7.67; N, 6.27. Found: C, 85.94; H, 7.60; N, 6.19%.
3-(4-Methoxyphenyl)isoquinoline (2u). Red solid, yield: 93%
(219 mg). M.p. 85–87 C. H NMR (CDCl3, 300 MHz) d 3.87 (s,
1
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3-Pentyl-9,10-dihydrobenzo[f]isoquinoline (2q). Yellow gum, 3H). 7.04 (d, J ¼ 8.7 Hz, 2H), 7.54 (t, J ¼ 7.8 Hz, 1H), 7.65 (t, J ¼
yield: 73% (183 mg). 1H NMR (CDCl3, 300 MHz) d 0.91 (t, J ¼ 6.9 6.9 Hz, 1H), 7.82 (d, J ¼ 7.8 Hz, 1H), 7.96 (d, J ¼ 11.7 Hz, 1H),
Hz, 3H), 1.25–1.52 (m, 4H), 1.71–1.81 (m, 2H), 2.79–2.94 (m, 7.98 (s, 1H), 8.09 (d, J ¼ 9.3 Hz, 2H), 9.30 (s, 1H). 13C NMR
6H), 7.15–7.39 (m, 3H), 7.47 (s, 1H), 7.77–7.83 (m, 1H), 8.39 (s, (CDCl3, 75 MHz) d 55.4, 114.2, 115.4, 126.7, 126.8, 127.4, 127.6,
1H). 13C NMR (CDCl3, 75 MHz) d 14.1, 22.6, 25.1, 28.5, 29.8, 128.2, 130.5, 132.2, 136.8, 151.0, 152.3, 160.1. IR (CHCl3, cmꢂ1):
31.6, 38.0, 116.7, 124.3, 127.2, 128.6, 129.2, 129.5, 132.0, 138.4, 1608, 1515, 1249, 834. MS (EI, m/z): 235 [M+]. Anal. calcd for
142.6, 147.6, 160.9. IR (CHCl3, cmꢂ1): 2955, 2930, 2857, 1603,
1545, 1451, 754. MS (EI, m/z): 251.1 [M+]. Anal. calcd for 5.79%.
C16H13NO: C, 81.68; H, 5.57; N, 5.95. Found: C, 81.78; H, 5.63; N,
C
18H21N: C, 86.01; H, 8.42; N, 5.57. Found: C, 86.29; H, 8.53; N,
5.78%.
7-Methoxy-3-propyl-9,10-dihydrobenzo[f]isoquinoline
7-Phenyl-[1,3]-dioxolo[4,5-g]isoquinoline (2v). Brown solid,
yield: 90% (224 mg). M.p. 111–112 ꢀC. 1H NMR (CDCl3, 300
(2r). MHz) d 5.96 (s, 2H), 6.97 (d, J ¼ 3.3 Hz, 1H), 7.08 (d, J ¼ 2.4 Hz,
1
Yellow gum, yield: 72% (182 mg). H NMR (CDCl3, 300 MHz) d 1H), 7.35–7.51 (m, 3H), 7.79 (s, 1H), 8.05 (d, J ¼ 6.9 Hz, 2H), 9.00
1.01 (t, J ¼ 7.4 Hz, 3H), 1.72–1.89 (m, 2H), 2.72–2.97 (m, 6H), (s, 1H). 13C NMR (CDCl3, 75 MHz) d 101.6, 102.7, 103.0, 116.3,
3.87 (s, 3H), 6.82 (d, J ¼ 2.1 Hz, 1H), 6.89 (dd, J ¼ 8.5 Hz and 2.3 124.9, 126.8, 127.2, 128.3, 128.8, 129.2, 135.0, 139.6, 148.3,
Hz, 1H), 7.43 (s, 1H), 7.75 (d, J ¼ 8.6 Hz, 1H), 8.36 (s, 1H). 13C 150.0, 150.3, 151.0. IR (CHCl3, cmꢂ1): 1600, 1481, 1459, 1232,
NMR (CDCl3, 75 MHz) d 13.9, 23.2, 25.1, 28.8, 39.3, 55.4, 113.0, 1038. MS (EI, m/z): 249 [M+]. Anal. calcd for C16H11NO2: C, 77.10;
113.8, 116.4, 124.5, 126.1, 128.3, 140.5, 161.0. IR (CHCl3, cmꢂ1): H, 4.45; N, 5.62. Found: C, 77.31; H, 4.37; N, 5.68%.
2960, 2932, 1602, 1464, 1259, 1045. MS (EI, m/z): 253 [M+]. Anal.
calcd for C17H19NO: C, 80.60; H, 7.56; N, 5.53. Found: C, 80.69; yield: 89% (234 mg). M.p. 152–153 ꢀC. 1H NMR (CDCl3, 300
7-(p-Tolyl)-[1,3]-dioxolo[4,5-g]isoquinoline (2w). Brown solid,
H, 7.55; N, 5.75%.
MHz) d 2.41 (s, 3H), 6.01 (s, 2H), 7.01 (s, 1H), 7.13 (s, 1H), 7.29
3-Butyl-7-methoxy-9,10-dihydrobenzo[f]isoquinoline
(2s). (d, J ¼ 8.1 Hz, 2H), 7.80 (s, 1H), 7.95 (d, J ¼ 8.1 Hz, 2H), 9.01 (s,
Yellow gum, yield: 72% (192 mg). H NMR (CDCl3, 300 MHz) d 1H). 13C NMR (CDCl3, 75 MHz) d 21.3, 101.6, 102.7, 103.0, 116.0,
0.89 (t, J ¼ 7.3 Hz, 3H), 1.29–1.40 (m, 2H), 1.62–1.72 (m, 2H), 124.8, 126.6, 129.5, 135.1, 136.6, 138.2, 148.2, 149.9, 150.3,
2.72–2.81 (m, 6H), 3.81 (s, 3H), 6.82 (dd, J ¼ 8.3 Hz and 2.6 Hz, 151.1. IR (CHCl3, cmꢂ1): 1598, 1480, 1456, 1224, 1035. MS (EI,
1H), 7.25 (d, J ¼ 2.7 Hz, 1H), 7.13 (d, J ¼ 8.3 Hz, 1H), 7.35 (s, 1H), m/z): 263 [M+]. Anal. calcd for C17H13NO2: C, 77.55; H, 4.98; N,
8.32 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 14.0, 22.6, 25.4, 27.7, 5.32. Found: C, 77.49; H, 4.78; N, 5.53%.
1
32.3, 37.9, 55.5, 109.9, 114.8, 116.6, 119.2, 129.3, 129.4, 130.6,
7-Methoxy-3-phenyl-9,10-dihydrobenzo[f]isoquinoline
(2x).
1
133.1, 142.3, 148.1, 158.8, 161.0. IR (CHCl3, cmꢂ1) 2962, 2930, Yellow gum, yield: 86% (247 mg). H NMR (CDCl3, 300 MHz) d
1601, 1463, 1257, 1042. MS (EI, m/z): 267 [M+]. Anal. calcd for 2.86–2.96 (m, 4H), 3.90 (s, 3H), 6.93 (dd, J ¼ 8.3 Hz and 2.5 Hz,
C
18H21NO: C, 80.86; H, 7.92; N, 5.24. Found: C, 80.96; H, 7.87; N, 1H), 7.24 (d, J ¼ 8.4 Hz, 1H), 7.30–7.57 (m, 5H), 7.98 (s, 1H), 8.02
5.56%.
(d, J ¼ 7.3 Hz, 1H), 8.59 (s, 1H). 13C NMR (CDCl3, 75 MHz) d 25.5,
7-Phenyl-3-(p-tolyl)-1,6-naphthyridine (2t). Yellow solid, yield: 27.6, 55.6, 110.0, 114.9, 127.0, 128.5, 128.8, 129.0, 129.5, 130.6,
1
70% (207 mg). M.p. 190–191 C. H NMR (CDCl3, 300 MHz) d 130.8, 132.9, 139.2, 143.0, 148.4, 158.9. IR (CHCl3, cmꢂ1): 2926,
ꢀ
2.38 (s, 3H), 7.02–7.60 (m, 7H), 8.12 (d, J ¼ 7.3 Hz, 2H), 8.18–8.34 2851, 1601, 1542, 1481, 1220, 771. MS (EI, m/z): 287.1 [M+]. Anal.
(m, 2H), 9.28 (s, 1H), 9.33 (s, 1H). 13C NMR (CDCl3, 75 MHz) d calcd for C20H17NO: C, 83.59; H, 5.96; N, 4.87. Found: C, 83.57;
21.3, 117.6, 122.6, 127.2, 129.0, 129.2, 130.1, 131.9, 134.1, 135.0, H, 6.09; N, 4.78%.
138.7, 138.9, 150.2, 152.8, 154.6, 154.9. IR (KBr, cmꢂ1) 2923,
4-(Naphthalen-2-yl)-2-phenylpyridine (2y). Yellow gum, yield:
2850, 1352, 810, 767. MS (EI, m/z): 296 [M+]. Anal. calcd for 93% (261 mg). H NMR (CDCl3, 300 MHz) d 7.35–7.54 (m, 6H),
1
C21H16N2: C, 85.11; H, 5.44; N, 9.45. Found: C, 85.13; H, 5.44; N, 7.74 (dd, J ¼ 8.5 Hz and 1.6 Hz, 1H), 7.82–7.93 (m, 1H), 7.91 (t, J
9.58%.
¼ 8.3 Hz, 2H), 8.00 (d, J ¼ 0.5 Hz, 1H), 8.05–8.13 (m, 3H), 8.74 (d,
General procedure for the catalyst-free synthesis of J ¼ 5.1 Hz, 1H). 13C NMR (CDCl3, 75 MHz) d 119.0, 120.5, 124.5,
compounds 2a, 2c, 2e, 2u–y. A mixture of ortho-alkynyl aryl/ 126.5, 126.8, 126.9, 127.2, 127.8, 128.5, 128.9, 129.0, 129.2,
vinyl aldehyde (1 mmol), benzamidine hydrochloride (1.1 133.5, 133.51, 135.7, 139.4, 149.3, 150.1, 158.1. IR (CHCl3,
mmol) and triethylamine (2.1 mmol) was irradiated in a closed cmꢂ1): 2924, 1621, 1222, 776. MS (EI, m/z): 281.1 [M+]. Anal.
ꢀ
vessel in a Synthos 3000 microwave reactor at 720 W (140 C calcd for C21H15N: C, 89.65; H, 5.37; N, 4.98. Found: C, 89.49; H,
and 14 bar) for 5 min. Aer completion of the reaction, as 5.21; N, 4.76%.
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General procedure for the multi-component synthesis of
compounds 2a, 2c, 2e, 2o, 2u,v using benzamidine hydrochlo-
ride. A mixture of halo aldehyde (1 mmol), 10 mol% CuI,
terminal alkyne (1.1 mmol), benzamidine hydrochloride
(1.1 mmol) and triethylamine (2.1 mmol) in DMF (1 mL) was
irradiated in a closed vessel in a Synthos 3000 microwave
reactor at 720 W (140 ꢀC and 14 bar) for 8 min. Aer completion
of the reaction, as indicated by TLC, the reaction mixture was
treated with water (40 mL) and then extracted with ethyl acetate
(40 mL). The organic portion was washed with water, dried over
anhydrous sodium sulfate and the solvent was removed to
obtain a crude product which on silica gel column chromato-
graphic purication using EtOAc/hexane (1 : 4) as eluent affor-
ded compounds 2a, 2c, 2e, 2o, 2u,v whose spectral data are
similar to those mentioned above.
Acknowledgements
We thank the Department of Science & Technology, New Delhi
for nancial support. K.S. thanks CSIR, New Delhi for the award
of Senior research fellowship (CSIR-SRF). We are grateful to
Director, CSIR-NEIST for his keen interests. We gratefully
acknowledge nancial support from CSIR-ORIGIN (CSC 0108),
CSIR-ACT (CSC0301) and CSIR-OSDD (HCP-0001) projects.
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