Polystyrene resin supported palladium(0) (Pd@PR) nanocomposite mediated regioselective synthesis of 4-aryl-1-alkyl/(2-haloalkyl)-1H-1,2,3-triazoles and their N-vinyl triazole derivatives from terminal alkynes

Article abstract of DOI:10.1039/c4ra15133j

An efficient general methodology has been developed for sequential one-pot synthesis of 4-aryl-1-alkyl-1H-1,2,3-triazoles influenced by polystyrene resin supported palladium(0) (Pd@PR) nanocomposite as a heterogeneous catalyst. The present work particularly emphasizes the synthesis of 4-aryl-1-(2-haloalkyl)-1H-1,2,3-triazoles through the selective mono-azidation of 1,2-dihaloethane and subsequent Pd@PR mediated 1,3-dipolar cycloaddition with terminal aryl alkynes. Potassium carbonate promoted dehydrohalogenation of synthesized 4-aryl-1-(2-haloalkyl)-1H-1,2,3-triazoles gave the corresponding N-vinyl derivatives (often used as building blocks for polymers) which are further utilized in the synthesis of 4-aryl-1-(2-arylalkenyl)-1H-1,2,3-triazoles following a Pd@PR catalyzed Heck coupling approach. Furthermore, microwave assisted one pot dehydrochlorination and Heck strategy was adopted to afford 4-phenyl-1-styryl-1H-1,2,3-triazole under Pd@PR catalyzed conditions using iodobenzene as a phenylating agent.

Full text of DOI:10.1039/c4ra15133j

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Polystyrene resin supported palladium(0) (Pd@PR)
nanocomposite mediated regioselective synthesis
of 4-aryl-1-alkyl/(2-haloalkyl)-1H-1,2,3-triazoles
and their N-vinyl triazole derivatives from terminal
alkynes†‡
Cite this: RSC Adv., 2015, 5, 11506
Received 24th November 2014
Accepted 8th January 2015
DOI: 10.1039/c4ra15133j
Arun K. Shil,ab Sandeep Kumar,ab Saurabh Sharma,ab Abha Chaudharya
ab
*
www.rsc.org/advances
and Pralay Das
An efficient general methodology has been developed for sequential thrust for the development of efficient methodologies for the
one-pot synthesis of 4-aryl-1-alkyl-1H-1,2,3-triazoles influenced by synthesis of naturally non-occurring 1,2,3-triazole deriva-
polystyrene resin supported palladium(0) (Pd@PR) nanocomposite as a tives. The syntheses are mainly based on Huisgen's 1,3-
heterogeneous catalyst. The present work particularly emphasizes dipolar cycloaddition between organic azides and
the synthesis of 4-aryl-1-(2-haloalkyl)-1H-1,2,3-triazoles through substituted alkynes.3 But the major challenge relies on the
the selective mono-azidation of 1,2-dihaloethane and subsequent regio-selective control over the thermal [3 + 2] cycloaddition
Pd@PR mediated 1,3-dipolar cycloaddition with terminal aryl alkynes. reaction which oen gives apparently inseparable mixture of
Potassium carbonate promoted dehydrohalogenation of synthesized unsymmetrical regioisomers. However, copper4 and ruthe-
4-aryl-1-(2-haloalkyl)-1H-1,2,3-triazoles gave the corresponding nium5 complexes catalyzed azide–alkyne 1,3-dipolar cyclo-
N-vinyl derivatives (often used as building blocks for polymers) which addition reaction (Cu-AAC and Ru-AAC) were accomplished
are further utilized in the synthesis of 4-aryl-1-(2-arylalkenyl)-1H- with improved regioselectivity to procure either 1,4- or 1,5-
1,2,3-triazoles following a Pd@PR catalyzed Heck coupling approach. disubstituted 1,2,3-triazoles exclusively (Scheme 1(A)).
Furthermore, microwave assisted one pot dehydrochlorination and Recently, charcoal impregnated Zn was efficiently applied in
Heck strategy was adopted to afford 4-phenyl-1-styryl-1H-1,2,3-tri- cycloaddition of arylazides and alkynes to synthesise 1,4-
azole under Pd@PR catalyzed conditions using iodobenzene as a disubstituted 1,2,3-triazoles.6 The transition metal catalyzed
phenylating agent.
regioselective 1,3-dipolar cycloaddition reaction have
established the basis of the ‘click chemistry’ and set a
wonderful platform for the application in post-synthetic
modications of the 1,2,3-triazole functional scaffolds.1,7
Moreover, inadequate commercial availability of organic
azides and the fact that low molecular weight organic azides
having low carbon to nitrogen ratio are considered to be
potential explosive, have signicantly restricted their appli-
cation in direct azide–alkyne cycloaddition. Ligand aided Pd-
catalysts were successfully employed for the synthesis of
1,2,3-triazoles starting from vinyl halides and sodium azide
(Scheme 1(A)).8 Nevertheless, the developed homogeneous
transition metal catalyzed methodologies bear the inherent
drawbacks such as use of costly air sensitive ligands/
catalysts, recyclability and metal contamination along with
the product.
However, terminal alkynes in presence of heterogeneous
palladium are the most unexplored catalytic candidate for
azide–alkyne cycloaddition reaction with in situ generated
alkyl azides. On the other hand the multistep synthetic
approaches have been targeted to derive N-vinyl and N-styryl-
1,2,3-triazoles via pyrolytic elimination of polymer supported
organo-sulphoxides or selenides.9 Whereas N-vinyl substituted
1. Introduction
Substituted 1,2,3-triazoles are ubiquitous structural motifs
found in a wide range of potent pharmaceutical compounds
and advanced materials (Fig. 1a), and have gained growing
interest in diversied research areas.1 In spite of their
remarkable metabolic stability, 1,2,3-triazoles have proven
amazing medicinal efficacy as non-nucleoside reverse tran-
scriptase inhibitors (Fig. 1b), anti-cancer (Fig. 1c) and anti-
HIV (Fig. 1d) agents.2 In recent years, the cutting edge intra
as well as trans-disciplinary demands have triggered a major
aNatural Product Chemistry and Process Development, CSIR-Institute of Himalayan
Bioresource Technology, Palampur-176061, Himachal Pradesh, India. E-mail:
pdas@ihbt.res.in; pdas_nbu@yahoo.com; Fax: +91-1894-230433
bAcademy of Scientic & Innovative Research, New Delhi, India
† Electronic supplementary information (ESI) available: Graphical representation
of Pd@PR catalyst preparation, recyclability experiment, typical experimental
procedures, 2D NMR spectral analysis of product 2 and copies of 1H NMR, 13C
NMR, and ESIMS spectra. See DOI: 10.1039/c4ra15133j
‡ IHBT Communication no. 3757.
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2. Results and discussion
Pd@PR nanocomposite (earlier known as SS-Pd) was previously
developed and well characterized in our laboratory.10c–f The
straightforward preparation procedure of Pd@PR nano-
composite encompasses in situ reduction of Pd(II) precursor to
Pd(0) and their simultaneous deposition over the polystyrene
matrix (Experimental section).
Initially, the optimization study for azide–alkyne cycloaddi-
tion (AAC) reaction among phenyl acetylene, dichloro ethane
(DCE) and sodium azide as test substrates was carried out under
Pd-catalyzed condition by varying solvents, catalyst loading,
temperature and reaction time, and the results were summa-
rized in Table 1. Increasing catalyst loading as well as NaN3
quantity in different solvents led to higher conversion,
unlike CH3CN. Among the solvents tested, DMF gave highest
yield of the product 1 when employed with Pd@PR (3 mol% Pd)
and 3 equiv. of NaN3 with in minimum reaction time 8 h
(Table 1, entry 10), and considered as optimized reaction
condition. Whereas, Pd(OAc)2 and heterogeneous Pd/C were
found to be lesser reactive than Pd@PR. However, catalyst
free reaction proceeded to afford traces or lower yield of the
product 1 (Table 1, entries 2–4), which further conrmed the
role of Pd@PR catalyst for the conversion. The Pd@PR catalyst
could be reused up to ve times with negligible loss of catalytic
activity (rst run, 68% yield; h run, 58% yield) (ESI†).
The set reaction condition was further explored for the
sequential one-pot [3 + 2] AAC reaction between alkynes and in
situ produced alkyl or benzyl azides (Caution! The small
molecular weight azides may cause explosion for higher scale
reactions) as outlined in Table 2. First, we attempted DCE as
alkyl halide source which underwent selective mono-azidation.
The aryl alkynes containing both the electron releasing as well
Fig. 1 1,2,3-trizole motif containing value added products.
1,2,3-triazole derivatives are the precursors for industrially
important functionalized polymers. The facile polymerization
of N-vinyl-1,2,3-triazoles under free radical condition moti-
vated chemists for large scale production of the electron rich
polymers.9a,b
As a part of our continuing efforts to broaden the applica-
bility of developed heterogeneous nanocatalysts,10 herein, we
describe Pd@PR nanocomposite catalyzed facile sequential
one-pot process for the regio-selective synthesis of 4-aryl-1-
alkyl-1H-1,2,3-triazoles starting from terminal aryl alkynes,
primary alkyl halides and sodium azide. The synthesized 4-aryl-
1-(2-haloalkyl)-1H-1,2,3-triazoles were quantitatively converted
to the corresponding 4-aryl-1-vinyl-1H-1,2,3-triazoles which
further utilized in Heck coupling reaction under the same
catalytic condition to afford 4-aryl-1-(2-arylethenyl)-1H-1,2,3-
triazoles.
Scheme 1 Synthesis of (A) 1,4-disubstituted 1,2,3-triazoles, (B) 1-styryl-1,4-disubstituted 1,2,3-triazoles.
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Table 1 Optimization of reaction condition for one-pot azide–alkyne cycloaddition reaction
Entry
Pd-catalyst [mol%]
NaN3 [equiv.]
Solvent
Temp. [ꢀC]
Time [h]
%Yielda
1
2
3
4
5
6
7
8
Pd@PR [2]
—
Pd@PR [3]
—
2
3
3
3
3
2
3
4
2
3
3
3
2
2
3
3
1,4-Dioxane
1,4-Dioxane
(CH2)2Cl2
DMF
1,4-Dioxane
PEG-400
Toluene
Toluene
CH3CN
DMA
DMF
DMF
DMF
DMF
DMF
DMF
90
90
10
12
12
8
8
8
8
8
8
8
8
8
8
8
10
10
42
Trace
Trace
26
51
47
53
55
38
58
62
68
52
60
57
53
100
100
100
100
100
100
90
100
100
100
100
110
100
100
Pd@PR [3]
Pd@PR [2]
Pd@PR [3]
Pd@PR [4]
Pd@PR [3]
Pd@PR [3]
Pd@PR [2]
Pd@PR [3]
Pd@PR [2]
Pd@PR [2]
Pd(OAc)2 [3]
Pd/C [3]
9
10
11
12
13
14
15
16
a
Isolated yields.
as electron withdrawing functional groups gave comparably and later (pathway B) substitution reaction (SN2) step involving
good yields (61–78%) of the desired 4-aryl-1-(2-chloroethyl)-1H- organo halide. However, treatment of commercially available
1,2,3-triazoles 2–8 (Table 2, entries 1–7). The regio-selectivity 4-phenyl-1H-1,2,3-triazole with 1,2-dichloroethane under the
i.e., 1,4-disubstitution pattern of the product was conrmed similar reaction condition did not produce 1-(2-chloroethyl)-4-
by 2D NMR spectral analysis of the product 2 (ESI†). Propargyl phenyl-1H-1,2,3-triazole 1, which ruled out pathway A.
benzoate participated smoothly under the standard reaction
The reported tedious synthetic procedures11 for N-vinyl-1H-
condition to produce the corresponding 1,2,3-triazole 9 in 73% 1,2,3-triazoles have urged us to develop an alternative route
yield (Table 2, entry 8). Both the heteroaromatic and poly- (Table 3). Here we utilized the synthesized 4-aryl-1-(2-haloethyl)-
aromatic alkynes were found remarkably reactive for the 1H-1,2,3-triazoles (Table 2) in milder base K2CO3 promoted
present PdAAC reaction to afford the desired 4-aryl-1-(2-chlor- facile dehydrochlorination to obtain corresponding 4-aryl-1-
oethyl)-1H-1,2,3-triazoles 10 and 11 in good yields (Table 2, ethenyl-1H-1,2,3-triazoles (21–29) in good to excellent yields
entries 9 and 10). Then we successfully tried 1-bromo-2- (Table 3).
chloroethane in place of DCE under the similar reaction
Thus the synthesized N-vinyl-1H-1,2,3-triazole derivatives
condition to obtain 12, 13, and 14 in moderate yields (Table 2, further open up a spurring opportunity for us to develop
entries 11 to 13) in apparently inseparable mixture of corre- an alternative method of Heck coupling strategy to synthesize 4-
sponding chloro and bromo derivatives. However formation of aryl-1-(2-arylethenyl)-1H-1,2,3-triazoles employing Pd@PR cata-
higher percentage of chloro-derivatives in all the three cases lyst (Table 3). Whereas, in previous reports costly organo S or Se
indicates the expected more prevalent SN2 at C–Br centre. In precursors and tiresome procedures greatly obstructed their
continuation to our effort to synthesise 4-aryl-1-(2-haloalkyl)- synthesis (Scheme 1(B)).12 The differently substituted electron
1H-1,2,3-triazoles, we further extended the optimized method- rich aryl iodides easily participated in the set protocol of Heck
ology to achieve 1-(2-hydroxyethyl) and 4-aryl-1-benzyl-1H-1,2,3- coupling reaction with 4-phenyl-1-vinyl-1H-1,2,3-triazole
triazoles (15–20) in satisfactory yields utilizing 2-bromoethanol following regio-selective terminal arylation to furnish moderate
and benzyl bromide respectively (Table 2, entries 14 to 19).
Mechanistically it is presumed that both the pathways A selectivity (conrmed by H NMR).
to good yields of the products 30–37 (Table 4) with high E
1
and B (Scheme 2) might follow to give the desired product
Further, we also targeted a sequential one-pot approach for
VI. Surface bound Pd–alkyne p-complex II collapses to form dehydro-halogenation and Heck coupling on 1-(2-chloroethyl)-
s-complex III which could lead through either pathway A or 4-phenyl-1H-1,2,3-triazole (1) with iodobenzene under micro-
pathway B analogous to the reported similar catalytic cycles.4b wave irradiation to procure 4-phenyl-1-styryl-1H-1,2,3-triazole
These pathways are distinguished by their earlier (pathway A) 30 in 51% yield (Scheme 3).
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Table 2 Pd@PR catalyzed one-pot synthesis of 4-aryl-1-alkyl-1H-1,2,3-triazoles
Entry
1
R1
R2-X
Products
Time [h]
%Yielda
4-CH3
(CH2)2Cl2
8
71
2
3
3-CH3
2-CH3
(CH2)2Cl2
9
9
63
56
(CH2)2Cl2
4
5
6
7
4-CN
4-CF3
4-F
(CH2)2Cl2
(CH2)2Cl2
(CH2)2Cl2
(CH2)2Cl2
12
10
10
12
78
63
61
64
2-NH2
8
9
Benzoyloxy
(CH2)2Cl2
(CH2)2Cl2
12
10
73
59
3-thiophene
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Table 2 (Contd.)
Entry
10
R1
R2-X
Products
Time [h]
12
%Yielda
6-methoxy-2-naphthyl
(CH2)2Cl2
67
11
12
H
(CH2)2ClBr
(CH2)2ClBr
10
8
63b
4-CH3
63b
13
14
15
6-methoxy-2-naphthyl
(CH2)2ClBr
12
10
10
66b
74c
77c
H
(CH2)2(OH)Br
(CH2)2(OH)Br
4-CH3
16
17
18
4-CN
(CH2)2(OH)Br
PhCH2Br
10
10
10
75c
73d
74d
H
4-CH3
PhCH2Br
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Table 2 (Contd.)
Entry
R1
R2-X
Products
Time [h]
%Yielda
19
4-CN
PhCH2Br
10
70d
a
All are isolated yields; reaction conditions: alkyne (100 mg), dichloroethane (DCE) (8 equiv.), NaN3 (3 equiv.), Pd@PR (3 mol% Pd), DMF, 100 ꢀC.
Reaction conditions: alkyne (100 mg), 1-bromo-2-chloroethane (8 equiv.), NaN3 (3 equiv.), Pd@PR (3 mol% Pd), DMF, 100 ꢀC, the product ratio of
b
chloro and bromo derivatives were calculated on the basis of 1H NMR. c Reaction conditions: alkyne (100 mg), 2-bromoethanol (5 equiv.), NaN3 (3
equiv.), Pd@PR (3 mol% Pd), DMF, 100 ꢀC. d Reaction conditions: alkyne (100 mg), benzylbromide (3 equiv.), NaN3 (3 equiv.), Pd@PR (3 mol% Pd),
DMF, 100 ꢀC.
standard protocol. The prepared 4-aryl-1-(2-chloroethyl)-1H-
1,2,3-triazoles were utilized in a facile K2CO3 promoted
dehydrochlorination to obtain the corresponding N-vinyl
derivatives as industrially consumable polymer precursor.
The terminally vacant vinyl functionality were successfully
utilized for Pd@PR catalysed Heck coupling with aryl iodides
to give a series of 4-aryl-1-(2-arylethenyl)-1H-1,2,3-triazole
Table 3 Dehydrohalogenation of 4-aryl-1-(2-haloalkyl)-1H-1,2,3-tri-
zoles to N-vinyl derivativesa
Scheme 2 Plausible mechanistic pathways for Pd-catalyzed azide–
alkyne cycloaddition reaction.
3. Conclusion
In summary, we have developed Pd@PR nanocomposite
catalyzed general single pot strategy for azide–alkyne cyload-
dition (AAC) reaction to synthesise 1,4-disubstituted-1,2,3-
triazoles in a regio-selective manner. The developed unprec-
edented PdAAC approach was specially moved towards 4-aryl-
1-(2-haloethyl)-1H-1,2,3-triazole
derivatives
synthesis.
However, other N-alkyl, benzyl substituted surrogates were
also procured either by extension or slight variation of the
a
All are isolated yields; reaction conditions: 4-aryl-1-(2-chloroethyl)- 1H-
1,2,3-triazole (100 mg), K2CO3 (2 equiv.), DMF (2 mL), 110 ꢀC, 3 h.
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Table 4 Pd@PR catalyzed Heck coupling for the synthesis of 4-aryl-1-
(2-arylalkenyl)-1H-1,2,3-trizolesa
nanocomposite, and could nd academic as well as industrial
interest.
4. Experimental section
General methods
Reagents of high quality were purchased from Sigma Aldrich
and Loba Cheime. Amberlite® IRA 900 Clꢁ resin used as solid
support was purchased from Acros Organics. Silica gel (60–120
mesh size) for column chromatography was procured from Sd
Fine-chem Ltd. Commercial reagents and solvents were of
analytical grade and were puried by standard procedures prior
to use. Thin layer chromatography was performed using pre
coated silica gel plates 60 F254 (Merck) in UV light detector.
Some experiments were performed on CEM Discover focused
microwave (2450 MHz, 300 W). The temperature of reactions in
monomode microwave experiments was measured by an inbuilt
infrared temperature probe that determined the temperature
on the surface of reaction ask. The sensor is attached in a
feedback loop with an on-board microprocessor to control the
rate of temperature rise. All the melting points are uncorrected
and were determined on a Barnstead Electrothermal 9100
capillary melting point apparatus. ESIMS spectra were deter-
mined using Waters Micromass Q-TOF Ultima Spectrometer. 1H
and 13C NMR spectra were recorded using a Bruker Avance 600
spectrometer operating at 600 MHz (1H) and 150 MHz (13C).
Spectra were recorded at 25 ꢀC in CDCl3 [residual CHCl3 (dH 7.26
ppm) or CDCl3 (dC 77.00 ppm) and MeOD (dH 3.30, 4.78 ppm) or
(dC 49.0 ppm) [residual (as international standard)] with TMS as
internal standard. Chemical shis were calculated according to
the residual solvents' standard peaks. Chemical shis were
recorded in d (ppm) relative to the TMS and NMR solvent signal,
coupling constants (J) are given in Hz and multiplicities of
signals are reported as follows: s, singlet; d, doublet; dd, double
doublet; t, triplet; q, quartet; m, multiplet.
a
All are isolated yields; reaction conditions: 4-aryl-1-vinyl-1,2,3-triazole
(100 mg), aryl iodide (1.5 equiv.), Pd@PR (5 mol% Pd), K2CO3 (3 equiv.),
DMF (2 mL), 120 ꢀC, 20 h; E/Z ratio was calculated on the basis of 1H
NMR.
Preparation of Pd@PR nanocomposite
The solution of 25 mg of NaBH4 in 10 mL of water (0.065 (M)
solution) was added to 1 g of polystyrene resin (Amberlite IRA
900 Clꢁ form) in a 25 mL round bottom ask. The mixture was
stirred for 4 h at room temperature. Then the resin was washed
with water till the pH became neutral and then with acetone to
remove water from the solid surface. The partially borohydride
exchanged resin beads were dried under reduced pressure. The
dried borohydride exchanged resin beads were added into the
warm (100 ꢀC) solution of palladium acetate (10 mg) in dry DMF
(3 mL) and the mixture was stirred for 1 h or till the brown
colored solution changed to colorless and simultaneously white
solid beads turned black. Aer cooling, the beads were ltered
through a cotton bed, washed with water and acetone, and dried
under reduced pressure.
Scheme 3 Microwave assisted one-pot synthesis of 4-phenyl-1-
vinyl-1H-1,2,3-triazole.
derivatives. In continuation Pd@PR catalysed microwave
assisted one pot dehydrohaloginative Heck coupling also
General experimental procedure for 4-aryl-1-(2-haloethyl)-1H-
1,2,3-triazole (1–20) synthesis
opened
a new scope to access N-vinyl-1H-1,2,3-triazole
analogues. The combined results provide an outstanding
example of catalytic efficiency and selectivity of Pd@PR
A mixture of aryl alkyne (100 mg), sodium azide (3 equiv.), 1,2-
dihaloethane (8 equiv.) and Pd@PR (3 mol% Pd) were taken in
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an oven dried 40 mL reaction vial with screw cap. Equal volume 7.83 (d, J ¼ 15 Hz, 1H), 7.88–7.90 (d, J ¼ 8.4 Hz, 2H), 8.09 (s, 1H);
(as compared to 1,2-dihaloethane) of dry DMF was added into it. 13C NMR (150 MHz, CDCl3) d 116.48, 121.57, 123.07, 125.88
The reaction mixture was then stirred under nitrogen in a pre (2C), 126.72 (2C), 128.51, 128.80, 128.92, 129.04 (2C), 130.04,
heated oil bath of temperature 100 ꢀC. Progress of the reaction 133.58, 148.04. ESIMS data: m/z calcd for [M + H]+ C16H14N3
was monitored by TLC. On completion, the cooled reaction 248.1187, obsd. 248.1178.
mixture was extracted with ethyl acetate (3 ꢂ 5 mL) by addition
of 2 mL of water and dried over anhydrous Na2SO4. Evaporation
of the combined organic layer followed by column chromatog-
Acknowledgements
raphy (hexane–ethyl acetate gradient) over silica gel (mesh 60– Authors are grateful to Director CSIR-IHBT for providing
200) afforded 4-aryl-1-(2-haloethyl)-1H-1,2,3-triazoles (1–14). necessary facilities during the course of work. The authors
Products 15–20 were also synthesised applying similar thank CSIR, New Delhi for nancial support as part of XII Five
procedure.
Year Plan programme under title ORIGIN (CSC-0108). AKS, SK,
SS and AC thank CSIR and UGC, New Delhi for awarding
fellowships.
General experimental procedure for 4-aryl-1-vinyl-1H-1,2,3-
triazole (21–29) synthesis
To a mixture of 4-aryl-1-(2-haloethyl)-1H-1,2,3-triazole (100 mg) Notes and references
and K2CO3 (2 equiv.) in an oven dried 40 mL reaction vial was
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added 2 mL of dry DMF. The reaction mixture was then stirred
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ꢀ
under nitrogen in a pre heated oil bath of temperature 110 C
for 3 hours. Progress of the reaction was monitored by TLC. On
completion, the cooled reaction mixture was extracted with
ethyl acetate (3 ꢂ 3 mL) by addition of 2 mL of water and dried
over anhydrous Na2SO4. Evaporation of the combined organic
layer followed by column chromatography (hexane–ethyl
acetate gradient) over silica gel (mesh 60–200) afforded 4-aryl-1-
vinyl-1H-1,2,3-triazoles (21–29).
General experimental procedure for 4-aryl-1-(2-arylvinyl)-1H-
1,2,3-triazoles (30–37) synthesis
To a mixture of 4-aryl-1-vinyl-1H-1,2,3-triazole (100 mg), aryl
iodide (1.5 equiv.), K2CO3 (2 equiv.) and Pd@PR (5 mol% Pd) in
an oven dried 40 mL reaction vial was added 2 mL of dry DMF.
The reaction mixture was then stirred under nitrogen in a pre
heated oil bath of temperature 120 ꢀC for 20 hours. Progress of
the reaction was monitored by TLC. On completion, the cooled
reaction mixture was extracted with ethyl acetate (3 ꢂ 5 mL) by
addition of 2 mL of water and dried over anhydrous Na2SO4.
Evaporation of the combined organic layer followed by column
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ꢀ
´
´
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