Regioselective, one-pot syntheses of symmetrically and unsymmetrically halogenated 2',6'-bispyrazolylpyridines

Article abstract of DOI:10.1055/S-0029-1217077

A series of regio-selectively 3'-, 4-, 4'-, 4'-, and 5'-halogenated heterocyclic 2',6'-bispyrazolylpyridine derivatives was prepared by a direct halogenation reaction in a simple, one-pot synthesis in good to excellent yield (in gram scale). This methodol

Full text of DOI:10.1055/S-0029-1217077

4
042
PAPER
Regioselective, One-Pot Syntheses of Symmetrically and Unsymmetrically
Halogenated 2¢,6¢-Bispyrazolylpyridines
R
S
egioselective
u
H
alogenatio
p
n
of
2
¢
,6
¢
-Bi
r
spyrazol
a
ylpyridine st im Basak, Pramiti Hui, Rajadurai Chandrasekar*
School of Chemistry, University of Hyderabad, Central University Post, Gachi Bowli, Hyderabad 500046, India
Fax +91(40)23134824; E-mail: rcsc@uohyd.ernet.in; E-mail: chandrasekar100@yahoo.com
Received 4 May 2009; revised 10 August 2009
in a six-step reaction from commercially available cit-
razinic acid.16
Abstract: A series of regio-selectively 3¢-, 4-, 4¢-, 4¢¢-, and 5¢-halo-
genated heterocyclic 2¢,6¢-bispyrazolylpyridine derivatives was
prepared by a direct halogenation reaction in a simple, one-pot syn- The 4¢-iodo-substitution on the bpp core, paved the way
thesis in good to excellent yield (in gram scale). This methodology
for further synthetic modification of the bpp unit by em-
yielded several symmetrically and asymmetrically substituted
ploying Suzuki and Sonogashira reaction conditions,
mono-, di-, tri-, and tetra-halo (bromo and iodo) substituted 2¢,6¢-
bispyrazolylpyridine cores, which may serve as potential intermedi-
ates for several metal-catalyzed coupling reactions.
which resulted in the generation of a series of 4¢-function-
alized bpp derivatives.1
6–19
Motivated by this result, in or-
der to extend the utility of the bpp unit, we have conducted
several pyrazole, pyridine and pyrazole/pyridine centered
halogen exchange reactions on the bpp core. The diverse-
ly halogenated products 1–14 thus obtained are potential
intermediates with which to engineer several tailor-made
bpp ligands (e.g., using transition-metal catalyzed reac-
tions) (Scheme 1).
Key words: heterocycles, halogenation, halogenated 2,6-bis(pyra-
zol-1-yl)pyridine, N-ligands, pyridines
In the area of heterocyclic chemistry, the 2¢,6¢-bispyra-
1
–3
zolylpyridine (bpp) unit is an important structural alter-
4
–12
native to the 2,2¢:6¢,2¢¢-terpyridine (terpy)
to its three readily available nitrogen-chelating sites
Figure 1). These tridentate heterocyclic ligand deriva-
tives have been attracting considerable attention as syn-
system due
In this article, we present a direct and efficient synthetic
strategy through which to achieve regioselective bromina-
tion and iodination reactions on the bpp in (i) a single
pyrazole ring, (ii) two pyrazole rings, (iii) a single pyra-
zole and pyridine unit, and (iv) two pyrazole and pyridine
units under optimum reaction conditions. Using the ap-
(
1
2
thetic building blocks in supramolecular chemistry,
1
2–14
15
photochemistry,
pounds,
biology, spin cross-over com-
4
,16–20
21–23
and polymers.
Since the first synthesis
1
of the bpp core by Goldsby et al., further functionaliza-
tion of its pyridine and pyrazole carbons remains a huge
challenge due to the lack of availability of diverse halo-
groups in the entire unit. Interestingly, the last 15 years
have witnessed a remarkable development in functional
group transformation reactions through aryl–halide C–X
4'
3'
5'
6'
5
2'
5''
N
N1
N
N
4
1''
4''
1
'
N
N
N
N
3
2
2
'' 3''
2
4
25
terpyridine (terpy)
(
X = halo) bond activation e.g., Suzuki, Sonogashira,
2',6'-bispyrazolylpyridine (bpp)
2
6
27
Stille and Buchwald coupling methods. Unfortunately,
due to the lack of diverse X atoms in the bpp unit, its
chemistry has been severely limited and has not devel-
oped as much as its counterpart ligand terpy. Hence,
there is an apparent demand for different regioselectively
halogenated bpp cores due to their importance as potential
synthetic intermediates in many transition-metal cata-
Figure 1
3
' and 5' selectivity
z
2
3
4
' selectivity
A
B
4
selectivity
X
4'' selectivity
2
4–27
lyzed cross-coupling reactions.
N
N
N
N
Y
N
To our surprise, with the exception of two articles, we
were unable to find reports describing the synthesis of ha-
logenated (on pyridine and pyrazole carbons) bpp-deriva-
tives. The first literature report describes the pyrazole-
centered dihalogenation reaction performed on a naked
4
and 4'' selectivity
1
2
3
4
5
6
7
X, Y, A, B = Br; Z = NH2
X, Y, A, B = Br, Z = H
X, Y, A, B = I; Z = NH2
X, Y, A, B = I; Z = H
X = Br ; Y = Br; Z = I
X = I; Y = I; Z = I
8
9
X = Br; Y = H; Z = I
X = Br; Y = I; Z = I
2
8
bpp core. Secondly, Chandrasekar and Ruben et al. have
10 X = Br; Y = H; Z = COOEt
11 X, Y = Br; Z = COOEt
12 X = I; Y = H; Z = COOEt
13 X, Y = I; Z = COOEt
reported the synthesis of a 4¢-iodo-substituted bpp moiety
X = I; Y = H; Z = I
14 X = I; Y = Br; Z = COOEt
SYNTHESIS 2009, No. 23, pp 4042–4048
x
x.
x
x
.
2
0
0
9
Advanced online publication: 22.10.2009
DOI: 10.1055/s-0029-1217077; Art ID: T09109SS
Georg Thieme Verlag Stuttgart · New York
Scheme 1
©

PAPER
Regioselective Halogenation of 2¢,6¢-Bispyrazolylpyridines
4043
proach mentioned above, many site-selective halogena- Na S O solution at pH 8. Extraction with chloroform
2
2
3
tion reaction at the 3¢-, 4-, 4¢-, 4¢¢-, and 5¢-positions of the gave NMR-pure compound 1 in an excellent gram scale
bpp core were effectively carried out under controlled re- yield (>99%) without any chromatographic purification.
action conditions, which resulted in quantitative prepara- Bromination at the pyrazole C-4 and C-4¢¢ positions are
tion (in grams) of a series of mono-, di-, tri- and tetra- evident from the absence of a multiplet peak at d = 6.48
1
halogenated (brominated and iodinated) bpp-derivatives ppm in the H NMR spectrum (which is the characteristic
1
–14 (Scheme 1).
region for these two protons). Our attempts to restrict the
halogenation to only the pyridine or pyrazole gave mix-
ture of products, as evidenced by LCMS analysis, where
the crude reaction mixture showed the presence of di-bro-
minated (m/z = 384) and tri-brominated (m/z = 462) com-
pounds, along with the tetra-brominated product 1 (m/z =
Our regioselective halogenation approach began with 4¢-
substituted 2¢,6¢-bispyrazolylpyridines 17–20. To build
these cores, we started our synthesis from the commer-
cially available citrazinic acid as per our previously re-
ported procedure. We used compounds 17–20 to
synthesize several brominated and iodinated products by
the direct exchange of pyridine-H and/or pyrazole-H by
halogen (Br or I) atoms in a regioselective manner in a
controlled single-pot quantitative preparation (Scheme 2).
1
6
5
42), making their separation difficult. Similarly, tetra-
iodinated product 3 was also prepared quantitatively on a
gram scale (99% yield) by using an excess (6 equiv) of io-
dinating agent. Furthermore, in order to facilitate the reac-
tion with sterically less crowded meta-di-halo groups,
deamination was performed by diazotization of com-
The pyrazole and pyrazole/pyridine centered regioselec-
tive halogenation is presented in Scheme 2. Generally, Br2
in acetic acid (BR) was used for bromination, whereas, an
pound 1 and 3 using NaNO , in the presence of a few
2
drops of concentrated H SO , under reflux, to obtain 2 and
2
4
I /HIO (IR) system was used for iodination; both types of
2
3
4
in 80–85% yield. The appearance of new resonance
reaction were performed in the presence of catalytic
amounts of sulfuric acid. At first, we studied the selectiv-
ity of reacting the NH -substituted bpp core of 18 with an
excess of bromination and iodination reagents in order to
generate a tetra-halogenated compound. We anticipated
that the two carbons ortho to the NH -group and the active
peaks at d = 8.49 and 8.99 ppm (4¢C-H) for compounds 2
and 4, respectively, in the H NMR spectra confirmed the
1
2
structure of the deaminated products.
In order to prepare the symmetrically and asymmetrically
halo-substituted bpp core, 19 was used as a starting mate-
rial since, in this case, an iodo group is already available
at the 4¢-position. Here, although the iodo-group is an
ortho and para-director, it was observed that (i) the C-4
and C-4¢¢ pyrazole carbons are more reactive towards bro-
mination than iodination (iodination requires elevated
temperatures) (ii) the deactivating nature of the 4¢-iodo
2
4
-position of the pyrazole will be halogenated. As per our
expectation, 3¢,4,4¢¢,5¢-tetrabrominated bpp-derivative 1
was indeed obtained by using six equivalents of brominat-
ing agent with 18 in acetic acid at 80 °C. The crude reac-
tion mixture forms a white flocculate with aqueous
IR = I2, HIO3, H+
BR = Br2, MeCOOH, H+
I
NH2
Br
Br
NaNO2
concd H2SO4
Br
Br
I
N
N
N
N
N
N
N
N
EtOH
benzene
reflux, 4 h
N
N
N
N
Br
Br
Br
Br
Br
Br
N
N
N
5
1
2
N
N
N
N
I
I
yield = 65%
yield = >99%
yield = 80%
N
6
yield = >99%
BR (2 equiv)
BR (6 equiv)
2 h
8
0 °C, 2 h
IR, 130 °C
2
4 h
HO
O
I
I
NH2
1) pyrazole
K, diglyme
O
O
HO
O
NaNO2
HCl, aq KI
NaN3, C2O2Cl2
TFA, K2CO3
1
10 °C
POCl3
4
NMe Cl
IR
4 h, 70 °C
1 week
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
2) LiOH, THF
Cl
I
N
N
N
N
N
Cl
HO
N
OH
7
19
18
17
16
BR (0.5 equiv)
h, 5 °C
citrazinic acid
yield = 55%
4
1
5
IR (6 equiv), 2 d
I
I
NH2
I
I
I
I
IR (2 equiv)
0 °C, 2 h
NaNO2
concd H2SO4
6
N
N
N
N
N
N
N
N
N
N
N
N
N
Br
Br
N
N
N
I
I
I
I
EtOH
benzene
reflux, 4 h
I
N
N
N
N
8
9
3
4
yield = 50%
yield = >99%
yield = >99%
yield = 85%
Scheme 2
Synthesis 2009, No. 23, 4042–4048 © Thieme Stuttgart · New York

4
044
S. Basak et al.
PAPER
group directs the halo-substitution only to the active pyra- ticipated that compound 20 will direct the halogenation
zole units and not to the pyridine. For example, the treat- only to the pyrazole ring and will facilitate the generation
ment of 19 with two equivalents of Br gave only a of symmetric and asymmetric mono- and di-halo-substi-
2
pyrazole centered (4- and 4¢¢-positions) mixed bromo- and tuted bpp. As per our expectation, by optimizing the tem-
iodo-substituted, symmetric bpp unit 5 as a white solid in perature, amount of halogen and addition rate, a series of
a decent 65% yield (Scheme 2). Formation of 5 was un- 4-bromo (10), 4,4¢¢-dibromo (11), 4-iodo (12), 4,4¢¢-di-
1
ambiguously confirmed by LCMS (m/z = 494.75) and H iodo (13) and a mixed asymmetric 4-iodo-4¢¢-bromo (14)
NMR spectroscopy (3 singlets). Furthermore, a symmet- substituted ester derivative of bpp were successfully syn-
ric 4-,4¢,4¢¢-triiodo-substituted bpp core 6 was also pre- thesized from 20 in a regiospecific manner. Compound 10
pared from 19 by using an excess (4 equiv) of iodinating was obtained selectively in an acceptable 25% yield using
reagent at 130 °C. Regular workup afforded compound 6, one equivalent of brominating agent under ice-cold condi-
in a quantitative >99% yield as colorless crystalline need- tions. Here, 11% of 11 was also obtained as a side-prod-
les (Scheme 2). Surprisingly, in neither case (5 and 6), uct. While increasing the reaction temperature to room
was halogenation of the pyridine ring 3¢- and 5¢-positions temperature and using two equivalents of Br gave 12% of
2
observed.
10 and 88% of 11. Further increase in the temperature up
to 100 °C with the use of two equivalents of Br afforded
2
Motivated by the pyrazole selective iodination reaction of
the white compound 11 in a quantitative yield (>99%). A
mono-iodinated bpp derivative 12 was successfully syn-
thesized in a modest yield of 42% (as colorless needles) at
1
9, by controlling the amount of iodinating reagent and
lowering the temperature, a limited monoiodination of a
single pyrazole ring was attempted. This was performed
by controlled slow addition (2 drops/15 min) of slightly
less than one equivalent of the iodinating mixture and by
keeping the reaction mixture at 70 °C. The reaction was
carefully followed by thin layer chromatography (after
neutralizing the reaction mixture), to stop the reaction be-
fore the formation of diiodinated side-product. After four
hours, regular work-up of the crude mixture gave the un-
7
1
0 °C using one equivalent of iodinating reagent. At
30 °C, increasing the amount of iodinating reagent up to
two equivalents gave compound 13 in quantitative yield
(
>99%). Analogous to the synthesis of 9, by treating 12
with an excess of Br at 80 °C, an asymmetrically substi-
2
tuted mixed bromo and iodo-substituted bpp core 14 was
synthesized effectively in a quantitative yield (>99%).
symmetrically C-4 substituted diiodo-2¢,6¢-bispyrazolyl It is essential to mention here that in all our halogenation
pyridine 7 in 55% yield (Scheme 2). Likewise, compound reactions the selective formation of mono and dihalo bpp
8
was synthesized by a restricted mono-bromination (0.5 was achieved by carefully monitoring the reaction by thin
equiv) of 19 under ice-cold conditions in a quantitative layer chromatography (after neutralizing the reaction
yield (50% from 19) as colorless needles. Taking advan- mixture). The mono-halo compounds always exhibit high-
tage of the available vacant pyrazole C-4 position in 8, via er R values than the starting material and the dihalo-com-
f
the iodination reaction, an attractive mixed 4-bromo- pounds show the highest R values. Most of the iodo-
f
4
¢,4¢¢-diiodo-substituted asymmetric bpp core 9 was syn- compounds could be readily crystallized in chloroform.
thesized quantitatively (99%).
In summary, we have developed, for the first time, a
In order to circumvent the tetra-halogenation reaction ob- straightforward route to the facile synthesis of a series of
served in 18, we synthesized ester derivatives of bpp 20 bromo and iodo-substituted tridentate bpp derivatives 1–
from 17 (Scheme 3). Further crystallization of 20 in 14 in a regioselective manner. The regioselectivity was ef-
chloroform by slow evaporation technique gave colorless fected either on a pyrazole unit alone or on both pyrazole
needle-like crystals in a quantitative yield (>99%). We an- and pyridine units together. In the pyridine unit, selective
O
O
O
O
O
O
O
O
O
O
IR
BR
+
+
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Br
N
N
N
N
I
I
I
Br
Br
N
N
N
N
N
N
20
11
1
2
13
10
yield = > 99%
excess BR, 80 °C
EtOH, H2SO4
3.5 h
O
O
Yield
Conditions
Yield
12
13
Conditions
5 °C
10
11
1
7
N
N
N
N
70 °C
30 °C
42%
-
28%
99%
25%
12%
-
11%
88%
99%
I
Br
N
1
4
r.t.
1
yield = > 99%
+
BR = Br2, MeCOOH, H
IR = I2, HIO3, H
+
100 °C
Scheme 3
Synthesis 2009, No. 23, 4042–4048 © Thieme Stuttgart · New York

PAPER
Regioselective Halogenation of 2¢,6¢-Bispyrazolylpyridines
4045
halogenation reactions at the 3¢-, 5¢- or 4¢-positions were bromine. The white precipitate was extracted with CHCl
(3 × 100
3
mL) and the organic extract was washed with brine (100 mL) and
performed by varying substituents at the 4¢-position. The
two pyrazole units were also activated at the 4- and/or 4¢¢-
positions selectively, which resulted in the generation of
mono or dihalo-substituted bpp cores. For example, two
novel tetrabromo- and tetraiodo-substituted bpp units (2
and 4) were synthesized. A mixed dibromo- and iodo-
bearing bpp (5) and a symmetrically substituted triiodo-
dried over anhydrous MgSO . The solvent was evaporated under re-
duced pressure to obtain product 1 without any chromatographic
purification.
4
Yield: 1.2 g (99%); white solid.
IR (KBr): 3466, 3366, 3111, 1744, 1605, 1561, 1539, 1470, 1387,
–
1
1
348, 1167, 1061, 951, 910, 783, 743, 631, 594 cm .
bispyrazolylpyridine 6 were also fruitfully synthesized. 1H NMR (400 MHz, CDCl
): d = 8.07 (s, 2 H, pyrazole), 7.73 (s,
3
2
H, pyrazole), 5.85 (s, 2 H, NH2).
Compound 5 may facilitate selective metal-catalyzed
functional group transformation at either the 4¢-iodo posi-
tion or the 4,4¢¢-dibromo positions due to their different
reactivities. Interestingly, we were able to prepare an un- LCMS: m/z calcd: 541.83; found: 541.82.
symmetrically substituted diiodinated product 7, where
1
3
C NMR (100 MHz, CDCl ): d = 153.5, 146.2, 142.1, 130.5, 96.5,
3
9
6.1.
Anal. Calcd for C H Br N : C, 24.38; H, 1.12; N, 15.51. Found: C,
1
1
6
4
6
the pyridine and pyrazole units each bear an iodo-func-
tionality. Synthetically challenging mixed bromo- and
2
4.48; H, 1.18; N, 15.65.
iodo-substituted bpp cores 9 and 14 were also prepared. 2¢,6¢-Bis(4,4¢¢-bromopyrazol-1,1¢¢-yl)-3¢,5¢-dibromopyridine (2)
To a solution of 1 (100 mg, 0.1845 mmol) in EtOH (5 mL), benzene
Compounds 1–14 are promising intermediates for many
(
1 mL), and concd H SO (0.5 mL), was added NaNO (0.5 g) and
2
4
2
site-selective organic functional group transformations
via transition-metal-catalyzed cross-coupling reactions.
We hope that these diverse C–X bonds appended to the
bpp may broadly open up the chemistry of the 2¢,6¢-
bispyrazolylpyridine unit. Further functional group trans- dried over MgSO and concentrated under reduced pressure. Com-
formations of 1–14 are in progress.
the mixture was heated under reflux for 4 h. After cooling to r.t., the
reaction mixture was quenched with aq NaHCO and Na CO solu-
3
2
3
tions until pH ~8 was reached. The white precipitate that formed
was extracted with CHCl (3 × 100 mL) and the organic extract was
3
4
pound 2 was separated from 1 (R = 0.61) by column chromatogra-
f
phy (silica gel; CH Cl ; R = 0.90).
2
2
f
1H and 13C NMR spectroscopic data were recorded on a Bruker
DPX 400 spectrometer with solvent proton or carbon as internal
Yield: 0.72g (80%); white solid.
IR (KBr): 3414, 3353, 3245, 1740, 1663, 1624, 1576, 1520, 1485,
1404, 1383, 1306, 1231, 1206, 1111, 1049, 963, 920, 829, 764, 633,
1
13
standards [CDCl : d = 7.26 ( H) and 77.0 ( C) ppm; DMSO-d : d =
3
6
1
13
–1
2
.50 ( H) and 40.0 ( C) ppm]. Deuterated solvents CDCl , and
421 cm .
3
DMSO-d were obtained from Aldrich and Merck respectively.
Column chromatography was performed using Merck silica gel
1
6
H NMR (400 MHz, CDCl ): d = 8.49 (s, 1 H, pyridine), 8.18 (s,
3
2
1
H, pyrazole), 7.78 (s, 2 H, pyrazole).
(particle size 100–200 mesh). LC mass spectrometry was performed
3
C NMR (100 MHz, CDCl ): d = 151.5, 145.6, 142.9, 130.3, 109.9,
on Shimadzu LCMS-2010A mass spectrometer. IR spectra were re-
corded on a JASCO FT/IR-5300 instrument. Elemental analyses
were recorded on a Thermo Finnigan Flash EA 1112 analyzer. For
thin-layer chromatography (TLC), silica gel plates Merck 60 F254
were used and compounds were visualized by irradiation with UV
3
9
6.9.
LCMS: m/z calcd: 526.81; found: 526.8.
Anal. Calcd for C H Br N : C, 25.08; H, 0.96; N, 13.29. Found: C,
2
1
1
5
4
5
5.18; H, 1.06; N, 13.45.
light. Pyrazole, citrazinic acid, and HIO were obtained from Ald-
3
rich. Potassium metals, TFA, Br and diglyme were purchased from
2
2
¢,6¢-Bis(4,4¢¢-iodopyrazol-1,1¢¢-yl)-4¢-amino-3¢,5¢-diiodopyri-
spectrochem PVT. LTD, Mumbai. EtOH and H SO were obtained
2
4
dine (3); Typical Iodination Procedure
4
charged in a round-bottomed flask containing AcOH (5 mL) and aq
H SO (30%, 1.0 mL). The flask was heated at 70 °C. A deep-violet
aqueous solution (10 mL) containing HIO (0.3 g, 1.77 mmol), I
from Merck. Ac O and NaNO were obtained from Qualigens Fine
2
2
¢-Amino-2¢,6¢-bispyrazolyl pyridine (18; 100 mg, 0.44 mmol) was
Chemicals, Mumbai. AcOH, NaN , benzene, CH Cl , hexane, pe-
3
2
2
troleum ether, CHCl and MeOH were obtained from Finar Chemi-
3
2
4
cals Limited, Ahmedabad, India. All solvent were distilled prior to
use. Oxalyl chloride (C O Cl ), I , LiOH, TMACl, POCl , anhy-
3
2
2
2
2
2
3
(0.91 g, 3.54 mmol) and two drops of concentrated H SO was pre-
2 4
drous MgSO , K CO , and KI were obtained from Avra Synthesis,
4
2
3
pared. This solution was added dropwise to the solution of 18 (dur-
ing the addition the temperature of the mixture rose to 130 °C). The
reaction mixture was stirred 1 d under an argon atmosphere. After
cooling to r.t., just enough aq Na S O was added to destroy any ex-
Hyderabad, India.
Compounds 18–21 were synthesized as described in a previously
reported procedure.16
2
2
3
cess iodine. The mixture was quenched with aq sat. NaHCO and
3
2
¢,6¢-Bis(4,4¢¢-bromopyrazol-1,1¢¢-yl)-4¢-amino-3¢,5¢-dibromopy-
then with aqueous Na CO solution until pH ~8 was reached. The
2
3
ridine (1); Typical Bromination Procedure
white precipitate that formed was extracted with CHCl3
4
¢-Amino-2¢,6¢-bispyrazolyl pyridine (18; 500 mg, 2.21 mmol) was
(3 × 50mL), dried over MgSO and evaporated under reduced pres-
4
charged in a round-bottomed flask with AcOH (5 mL) and aq
H SO (10%, 1.5 mL). The reaction flask was heated at 70 °C. Sep-
sure. The crude solid mixture was washed with cold CHCl to re-
3
2
4
move yellow colored impurities and to afford product 3 in pure
form.
arately, a solution of Br (density = 3.11 g/mL, 0.68 mL, 13.26
mmol) dissolved in AcOH (10 mL) was slowly added into the flask
dropwise. When half of this solution (5 mL) was added, a dense
2
Yield: 0.32 g (>99%); white powder.
orange-yellowish solution was formed. Then the Br solution was
IR (KBr): 3443, 3316, 3129, 2917, 1605, 1543, 1512, 1453, 1406,
2
–
1
added quicker and the temperature rose to 80 °C. The mixture was
allowed to stir for 2 h. After cooling to r.t. the mixture was quenched
with aq NaHCO and then Na CO solutions until pH ~8 was
1167, 1026, 974, 937, 907, 631, 602 cm .
1
H NMR (400 MHz, CDCl ): d = 8.02 (s, 2 H, pyrazole), 7.76 (s,
3
3
2
3
2 H, pyrazole), 6.03 (s, 2 H, NH2).
reached. Just enough Na S O was then added to destroy any excess
2
2
3
Synthesis 2009, No. 23, 4042–4048 © Thieme Stuttgart · New York

4
046
S. Basak et al.
PAPER
1
3
C NMR (100 MHz, CDCl ): d = 158.0, 150.9, 145.9, 134.7, 71.0,
IR (KBr): 3094, 2924, 1728, 1586, 1564, 1516, 1451, 1377, 1337,
1254, 1182, 1036, 951, 847, 804, 735, 644, 596, 536 cm .
3
–
1
5
9.6.
1
LCMS: m/z calcd: 729.82; found: 729.0.
H NMR (400 MHz, CDCl ): d = 8.57 (s, 2 H), 8.24 (s, 2 H), 7.75
3
(
1
s, 2 H).
Anal. Calcd for C H I N : C, 18.10; H, 0.83; N, 11.52. Found: C,
11
6
4
6
3
1
8.05; H, 0.88; N, 11.68.
C NMR (100 MHz, CDCl ): d = 148.8, 147.6, 131.7, 118.6, 109.1,
3
6
0.8.
2
¢,6¢-Bis(4,4¢¢-iodopyrazol-1,1¢¢-yl)-3¢,5¢-diiodopyridine (4)
LCMS: m/z calcd: 588.78; found: 588.80.
To a solution of 3 (100 mg, 0.137 mmol) in EtOH (5 mL), benzene
1 mL), and concd H SO (0.5 mL), was added NaNO (0.5 g). The
Anal. Calcd for C H I N : C, 22.43; H, 1.03; N, 11.89. Found: C,
(
11 6 3
5
2
4
2
2
2.48; H, 1.09; N, 12.05.
mixture was heated to reflux for 4 h. After cooling the reaction mix-
ture to r.t., the solvents were evaporated in a rotary evaporator. The
reaction mixture was quenched with aq NaHCO and Na CO solu-
tions until pH ~8 was reached. The off-white precipitate formed was
extracted with CHCl (3 × 50mL) and the combined organic frac-
tion was dried over MgSO . The solvent was evaporated using a ro-
tary evaporator to give the yellow crude compound. Compound 4
was purified by passing the crude compound through a short silica
bed (EtOAc–PE, 3:7), followed by evaporating the solvent under re-
duced pressure. The obtained yellow solid was washed with cold
CHCl3.
2
¢-(4-Iodopyrazol-1-yl)-6¢-(pyrazol-1¢¢-yl)-4¢-iodopyridine (7)
3
2
3
Prepared according to the general bromination protocol using 19
100 mg, 0.30 mmol) in AcOH (5 mL), and aq H SO (30%, 1.0
(
2
4
3
mL). A deep-violet aqueous solution (10 mL) containing HIO3
4
(
0.02 g, 0.11 mmol), I (0.06 g, 0.24 mmol) and two drops of concd
2
H SO was slowly added into the flask dropwise in such a way that
2
4
the iodine was consumed (disappearance of violet color), before
adding the next drop (2 drops/15 min for 4 h). When half of this so-
lution (5 mL) was added, the I solution was added faster, and the
2
temperature was maintained at 70 °C. The reaction mixture was
stirred for 4 h under argon, then compound 7 was isolated from the
Yield: 83 mg (85%); white solid.
IR (KBr): 2919, 1851, 1740, 1703, 1615, 1537, 1472, 1412, 1348,
unreacted 19 (R = 0.12) by column chromatography (silica gel;
f
–
1
1
294, 1208, 1128, 1036, 939, 721, 604 cm .
CH Cl –hexane, 3:2; R = 0.23).
2
2
f
1
H NMR (400 MHz, CDCl ): d = 8.99 (s, 1 H, py), 8.18 (s, 2 H,
Yield: 75 mg (55%); white solid.
3
pyrazole), 7.79 (s, 2 H, pyrazole).
1
IR (KBr): 3096, 1586, 1566, 1522, 1458, 1397, 1375, 1181, 1038,
3
–1
C NMR (100 MHz, CDCl ): d = 164.1, 148.6, 146.5, 134.0, 80.7,
961, 843, 754, 731, 600 cm .
3
6
0.5.
1
H NMR (400 MHz, DMSO-d ): d = 9.16 (s, 1 H), 9.01 (s, 1 H),
6
LCMS: m/z calcd: 714.81; found: 713.80.
8.13 (s, 1 H), 8.06 (s, 1 H), 7.96 (s, 1 H), 7.87 (s, 1 H), 6.63 (s, 1 H).
1
3
Anal. Calcd for C H I N : C, 18.48; H, 0.71; N, 9.80. Found: C,
C NMR (100 MHz, DMSO-d ): d = 149.8, 149.0, 148.1, 143.7,
6
11
5 4
5
1
8.39; H, 0.82; N, 9.96.
133.1, 129.2, 118.1, 117.2, 111.6, 109.3, 63.2.
LCMS: m/z calcd: 462.88; found: 462.45.
2
¢,6¢-Bis(4,4¢¢-bromopyrazol-1,1¢¢-yl)-4-iodopyridine (5)
Anal. Calcd for C H I N : C, 28.53; H, 1.52; N, 15.13. Found: C,
Performed according to the general bromination protocol using 19
11 7 2
5
2
8.65; H, 1.48; N, 15.31.
(100 mg, 0.3 mmol), AcOH (5 mL), and aq H SO (10%, 1.0 mL),
2
4
and a solution of Br (density = 3.11 g/mL, 0.03 mL, 0.6 mmol) dis-
2
2
¢-(4-Bromopyrazol-1-yl)-6¢-(pyrazol-1¢¢-yl)-4¢-iodopyridine (8)
solved in AcOH (5 mL). The mixture was stirred for 2 h then the
crude mixture was purified by chromatography (silica gel; CH Cl –
According to the general bromination protocol, 19 (100 mg, 0.296
mmol), AcOH (5 mL) and aq H SO (10%, 1.0 mL) were mixed and
the flask was cooled to ice-cold temperature. A solution of Br2
2
2
hexane; R = 0.45), to isolate compound 5. Alternatively, in our sec-
2
4
f
ond batch reaction, in order to avoid column chromatography, the
crude solid compound was washed with hot hexane to obtain 5 in
pure form in 40% yield (Note: the compound 5 is slightly soluble in
hot hexane).
(
density = 3.11 g/mL, 0.0075 mL, 0.146 mmol) was taken by micro
pipette and dissolved in AcOH (4 mL) and was very slowly added
into the solution of 19 dropwise in such a way that the bromine was
consumed before adding the next drop. After addition of the whole
brominating reagent, the mixture was stirred for 4 h to give a white
precipitate. The crude compound was purified by column chroma-
tography (silica gel; CH Cl –hexane, 3:2) to isolate product 8
Yield: 94 mg (65%); white solid.
IR (KBr): 3138, 3096, 2855, 1717, 1589, 1566, 1454, 1381, 1345,
–
1
1
262, 1182, 1036, 957, 847, 735, 644, 596 cm .
2
2
1
(R
f
= 0.27) in a second fraction and further recrystallized from
H NMR (400 MHz, DMSO-d ): d = 9.3 (s, 2 H), 8.08 (s, 2 H), 7.99
6
CHCl to give analytically pure crystals. [First fraction contains 5
3
(
1
s, 2 H).
(
Rf = 0.45) in trace amounts].
3
C NMR (100 MHz, DMSO-d ): d = 149, 143.9, 129.3, 117.7,
6
Note: Reduction of addition time of bromine leads to lower yields
of 8 and increases the amount of dibromination in the 4- and 4¢¢-po-
sitions to form 5.
1
11.9, 97.0.
LCMS: m/z calcd 494.75; found: 494.75.
Anal. Calcd for C H Br IN : C, 26.70; H, 1.22; N, 14.15. Found:
C, 26.70; H, 1.22; N, 14.15.
1
1
6
2
5
Yield: 61 mg (50%); white needles.
IR (KBr): 2922, 2857, 1589, 1557, 1462, 1387, 1202, 1038, 963,
–
1
8
53, 808, 752, 600 cm .
2
¢,6¢-Bis(4,4¢¢-iodopyrazol-1,1¢¢-yl)-4¢-iodopyridine (6)
1
Prepared according to the general iodination protocol using 19 (100
H NMR (400 MHz, CDCl ): d = 8.53 (s, 1 H), 8.50–8.49 (d,
3
3
3
mg, 0.30 mmol), AcOH (5 mL), and aq H SO (30%, 1.0 mL), and
J = 2.4 Hz, 1 H, pyrazole), 8.29 (s, 1 H), 8.20 (s, 1 H), 7.77 (d,
J = 1.2 Hz, 1 H), 7.7 (s, 1 H), 6.50 (m, 1 H).
2
4
a deep-violet aqueous solution (10 mL) containing HIO (0.16 g, 0.9
3
mmol), I (0.46 g, 1.8 mmol) and two drops of concd H SO . The
analytically pure compound 6 was obtained by recrystallization of
the crude product from CHCl3.
13
2
2
4
C NMR (100 MHz, CDCl ): d = 149.7, 148.9, 143.2, 143.0, 127.3,
3
1
27.2, 119.0, 117.9, 109.0, 108.6, 97.1.
LCMS: m/z calcd: 416.02; found: 415.1.
Yield: 0.17 g (>99%); transparent needles.
Synthesis 2009, No. 23, 4042–4048 © Thieme Stuttgart · New York

PAPER
Regioselective Halogenation of 2¢,6¢-Bispyrazolylpyridines
4047
Anal. Calcd for C H BrIN : C, 31.76; H, 1.76; N, 16.83. Found: C,
Anal. Calcd for C H Br N O : C, 38.12; H, 2.51; N, 15.88. Found:
11
7
5
14 11
2
5
2
3
1.66; H, 1.75; N, 16.95.
C, 38.26; H, 2.48; N, 15.96.
2
¢-(4-Bromopyrazol-1-yl)-6¢-(4¢¢-iodopyrazol-1¢¢-yl)-4¢-iodopy-
Ethyl 2¢-(4-Bromopyrazol-1-yl)-6¢-(pyrazol-1¢¢-yl)isonicotinate
(10)
ridine (9)
Prepared according to the general iodination protocol using 8 (35
Prepared according to the general bromination protocol, 20 (150
mg, 0.084 mmol), AcOH (5 mL), and aq H SO (30%, 1.0 mL).
mg, 0.56 mmol), AcOH (5 mL) and aq H SO (10%, 1.0 mL). The
2
4
2
4
Separately, a deep-violet aqueous solution (10 mL) containing HIO3
0.015 g, 0.015 mmol), I (0.043 g, 0.168 mmol) and two drops of
flask was cooled to an ice-cold temperature. Separately, a solution
(
of Br (density = 3.11 g/mL, 0.028 mL, 0.56 mmol) dissolved in
2
2
concd H SO , was slowly added into the solution of 8 dropwise at
AcOH (4 mL) was very slowly added into the solution of 20 drop-
wise. The mixture was stirred for 4 h, then the crude compound was
2
4
7
0 °C until the spot of 8 disappeared in TLC [R = 0.27 (CH Cl –
f
2
2
hexane, 3:2)]. The CHCl extract was evaporated under reduced
separated by column chromatography (EtOAc–PE, 1:4; R = 0.40)
3
f
pressure to isolate compound 9.
to isolate compound 10. The 1st fraction contained ethyl 2¢,6¢-
bis(4,4¢¢-bromopyrazol-1,1¢¢-yl)isonicotinate [11; R = 0.50; 21 mg
f
Yield: 45 mg (>99%); white solid.
(
11% yield)].
–
1
IR (KBr): 3096, 1589, 1456, 1381, 1182, 1036, 957, 735, 596 cm .
Yield: 48 mg (25%); white solid.
1
H NMR (400 MHz, CDCl ): d = 8.55 (s, 1 H), 8.52 (s, 1 H), 8.24
3
IR (KBr): 3447, 3246, 2924, 2853, 1742, 1657, 1626, 1520, 1466,
(
s, 2 H), 7.74 (s, 1 H), 7.70 (s, 1 H).
–
1
1
402, 1306, 1262, 1186, 1046, 989, 831, 772, 633 cm .
1
3
C NMR (100 MHz, CDCl ): d = 148.9, 148.8, 147.6, 143.4, 131.7,
3
1
3
H NMR (400 MHz, CDCl ): d = 8.54 (s, 1 H), 8.51–8.50 (d, J = 4
3
1
27.3, 118.6, 118.0, 109.1, 97.3, 60.9.
Hz, 1 H), 8.38 (s, 1 H), 8.30 (s, 1 H), 7.78 (s, 1 H), 7.71 (s, 1 H),
LCMS: m/z calcd 541.91; found: 541.85.
6
.51 (m, 1 H), 4.43–4.48 (q, J = 7.1 Hz, 2 H), 1.42–1.45 (t, J = 7.0
Hz, 3 H).
Anal. Calcd for C H BrI N : C, 24.38; H, 1.12; N, 12.92. Found:
C, 24.27; H, 1.18; N, 13.12.
1
1
6
2
5
13
C NMR (100 MHz, CDCl ): d = 163.8, 150.7 149.9 143.8, 143.2,
3
1
43.0, 127.3, 127.2, 109.7, 108.6, 97.1, 62.3, 14.2.
Ethyl 2¢,6¢-Bis(pyrazol-1,1¢¢-yl)isonicotinate (20)
¢,6¢-Dipyrazolylisonicotinic acid (17; 150 mg, 0.59 mmol) was dis-
solved in EtOH (100 mL) and concd. H SO (2 mL). The mixture
LCMS: m/z calcd 362.18; found: 363.25.
2
Anal. Calcd for C H BrN O : C, 46.43; H, 3.34; N, 19.34. Found:
2
4
14 12
5
2
was heated to reflux for 4 h, then the excess EtOH was removed un-
C, 46.61; H, 3.31; N, 19.62.
der vacuum to give an oily liquid. To this, H O (100 mL) was added
2
(
(
to remove H SO ) and the solution was extracted with CHCl
3 × 50 mL). The organic fraction was washed with brine, dried
Ethyl 2¢-(4-Iodopyrazol-1-yl)-6¢-(pyrazol-1¢¢-yl)isonicotinate
(12)
2
4
3
over MgSO and concentrated under reduced pressure to yield a col-
orless oil that hardened upon standing.
Prepared according to the general iodination protocol using 20 (150
mg, 0.53 mmol), AcOH (5 mL) and aq H SO (30%, 1.0 mL), and
4
2
4
a deep-violet aqueous solution (10 mL) containing HIO (0.04 g,
3
Yield: 0.15 g (95%); white solid.
0
.21 mmol), I (0.11 g, 0.42 mmol) and two drops of concentrated
2
IR (KBr): 3129, 1721, 1616, 1574, 1524, 1462, 1399, 1285, 1242,
H SO . The crude compound was isolated by column chromatogra-
2
4
1
208, 1142, 1094, 1053, 949, 916, 887, 787, 770, 648, 608, 490
phy on silica gel (EtOAc–PE, 1:9; R = 0.43) to give 12. As a side
f
–
1
cm .
product, 4,4¢¢-diiodinated compound 13 was obtained by collecting
1
3
the first fraction (R = 0.58; 79 mg, 28% yield). Both compounds
H NMR (400 MHz, CDCl ): d = 8.51–8.50 (d, J = 2.8 Hz, 2 H),
f
3
3
were readily crystallized in CHCl3.
8
2
.33 (s, 2 H), 7.76 (s, 2 H), 6.48 (m, 2 H), 4.46–4.40 (q, J = 8 Hz,
3
H, CH ), 1.48–1.40 (t, J = 7.2 Hz, 3 H, CH ).
2
3
Yield: 90 mg (42%); colorless needles.
1
3
C NMR (100 MHz, CDCl ): d = 163.9, 150.7, 143.5, 142.8, 127.2,
3
IR (KBr): 3111, 2980, 2863, 1811, 1726, 1616, 1574, 1530, 1466,
1
09.1, 108.4, 64.2, 14.2.
–1
1
399, 1287, 1242, 1148, 1098, 1044, 943, 887, 770, 600 cm .
LCMS: m/z calcd: 283.29; found: 284.00.
1
H NMR (400 MHz, CDCl ): d = 8.58 (s, 1 H), 8.52 (s, 1 H), 8.37
3
(
1
3
s, 1 H), 8.29 (s, 1 H), 7.78 (s, 1 H), 7.75 (s, 1 H), 6.50–6.51 (m,
Anal. Calcd for C H N O : C, 59.36; H, 4.63; N, 24.72. Found: C,
14
13
5
2
H), 4.42–4.47 (q, J = 7.2 Hz, 2 H, CH ), 1.41–1.45 (t, J = 7.2 Hz,
5
9.18; H, 4.67; N, 24.85.
2
H).
Ethyl 2¢,6¢-Bis(4,4¢¢-bromopyrazol-1,1¢¢-yl)isonicotinate (11)
Prepared according to the general bromination protocol using 20
13
C NMR (100 MHz, CDCl ): d = 163.8, 150.8, 149.8, 147.4, 143.8,
3
1
42.9, 131.7, 127.3, 109.8, 108.7, 108.6, 62.3, 60.6, 14.2.
(
150 mg, 0.56 mmol), AcOH (5 mL) and aq H SO (10%, 1.0 mL),
2 4
LCMS: m/z calcd 409.00; found: 409.75.
and a solution of Br (density = 3.11 g/mL, 0.058 mL, 1.12 mmol)
2
dissolved in AcOH (10 mL). The mixture was stirred for 4 h. The
Anal. Calcd for C H IN O : C, 41.10; H, 2.96; N, 17.12. Found:
1
4
12
5
2
CHCl extract was evaporated under reduced pressure to give 11.
C, 41.26; H, 2.85; N, 17.28.
3
Yield: 0.26 g (>99%); white solid.
Ethyl 2¢,6¢-Bis(4,4¢¢-iodopyrazol-1,1¢¢-yl)isonicotinate (13)
Prepared according to the general iodination protocol using 20 (150
mg, 0.53 mmol), AcOH (5 mL) and aq H SO (30%, 1.0 mL), and
IR (KBr): 2924, 2853, 1732, 1616, 1574, 1456, 1240, 1179, 965,
–
1
5
96 cm .
2
4
1
a deep-violet aqueous solution (10 mL) containing HIO (0.09 g,
H NMR (400 MHz, CDCl ): d = 8.56 (s, 2 H), 8.36 (s, 2 H, py),
3
3
0
.52 mmol), I (0.27 g, 1.06 mmol) and two drops of concd H SO .
2 2 4
7
.74 (s, 2 H), 4.44–4.49 (q, J = 8.0 Hz, 2 H, CH ), 1.42–1.46 (t,
2
The obtained white precipitate of 13 was readily crystallized from
CHCl3.
J = 6.0, 3.0 Hz, 3 H).
1
3
C NMR (100 MHz, CDCl ): d = 163.6, 150.0, 144.0 143.4, 127.3,
3
Yield: 280 mg (>99%); colorless needles.
1
09.2, 97.4, 62.4, 14.2.
IR (KBr): 3102, 2922, 2855, 1786, 1725, 1618, 1576, 1458, 1179,
LCMS: m/z calcd 441.08; found: 442.00.
–
1
1
046, 941, 766, 600 cm .
Synthesis 2009, No. 23, 4042–4048 © Thieme Stuttgart · New York

4
048
S. Basak et al.
PAPER
1
H NMR (400 MHz, CDCl ): d = 8.58 (s, 2 H), 8.34 (s, 2 H), 7.77
(5) Chelucci, G.; Thummel, R. P. Chem. Rev. 2002, 102, 3129.
(6) (a) Lehmann, U.; Henze, O.; Schlüter, A. D. Chem. Eur. J.
1999, 5, 854. (b) Hofmeier, H.; Schubert, U. S. Chem. Soc.
Rev. 2004, 33, 373.
3
3
3
(
s, 2 H), 4.43–4.49 (q, J = 7.2 Hz, 2 H, CH ), 1.42–1.46 (t, J = 7.2
2
Hz, 3 H).
1
3
C NMR (100 MHz, CDCl ): d = 163.6, 149.8, 147.6, 144.0, 131.7,
3
(7) Jameson, D. L.; Blaho, J. K.; Kruger, K. T.; Goldsby, K. A.
1
09.3, 62.4, 60.9, 14.3.
Inorg. Chem. 1989, 28, 4312.
8) Heller, M.; Schubert, U. S. Eur. J. Org. Chem. 2003, 947.
9) Fallahpour, R.-A. Synthesis 2003, 155.
LCMS: m/z calcd 535.90; found: 537.00.
(
(
Anal. Calcd for C H I N O : C, 31.43; H, 2.07; N, 13.09. Found:
C, 31.36; H, 2.11; N, 13.15.
14
11 2
5
2
(
(
10) Constable, E. C. Chem. Soc. Rev. 2007, 36, 246.
11) Sauvage, J. P.; Collin, J. P.; Chambron, J. C.; Guillerez, S.;
Udret, C.; Balzani, V.; Barigelletti, F.; De Cola, L.;
Flamigni, L. Chem. Rev. 1994, 94, 993.
Ethyl 2¢-(4-Bromopyrazol-1-yl)-6¢-(4¢¢-iodopyrazol-1¢¢-yl)iso-
nicotinate (14)
Prepared according to the general bromination protocol using 12
(
(
12) Lehn, J.-M. Supramolecular Chemistry. Concepts and
Perspectives; Wiley-VCH: Weinheim, 1995.
(
100 mg, 0.24 mmol), AcOH (5 mL) and aq H SO (10%, 1.0 mL),
2 4
13) Coronado, E.; Delhaés, P.; Gatteschi, D.; Miller, J. S.
Molecular Magnetism: From Molecular Assemblies to the
Devices, NATO ASI Series E, Vol. 321; Kluwer Academic
Publishers: Dordrecht, 1996.
and a solution of Br (density = 3.11 g/mL, 0.058 mL, 1.12 mmol)
dissolved in AcOH (10 mL). The obtained white solid product 14
was readily crystallized from CHCl3.
2
Yield: 0.1 g (99%); transparent needles.
(
14) Ruben, M.; Breuning, E.; Barboiu, M.; Gisselbrecht, J. P.;
IR (KBr): 3098, 2917, 1771, 1734, 1618, 1574, 1456, 1379, 1238,
Lehn, J.-M. Chem. Eur. J. 2003, 9, 291.
(15) Trawick, B. N.; Daniher, A. T.; Bashkin, J. K. Chem. Rev.
1998, 98, 939.
–
1
1
179, 1044, 965, 768, 646, 596 cm .
1
H NMR (400 MHz, CDCl ): d = 8.60 (s, 1 H), 8.57 (s, 1 H), 8.36
3
(
(
(
(
(
16) Rajadurai, C.; Schramm, F.; Brink, S.; Fuhr, O.; Kruk, R.;
Ghafari, M.; Ruben, M. Inorg. Chem. 2006, 45, 10019.
17) Rajadurai, C.; Fuhr, O.; Kruk, R.; Ghafari, M.; Hahn, H.;
Ruben, M. Chem. Commun. 2007, 2636.
18) Rajadurai, C.; Qu, Z.; Fuhr, O.; Balaji, G.; Kruk, R.; Ghafari,
M.; Ruben, M. J. Chem. Soc., Dalton Trans. 2007, 3531.
19) Chandrasekar, R.; Schramm, F.; Fuhr, O.; Ruben, M. Eur. J.
Inorg. Chem. 2008, 2649.
(
s, 2 H), 7.78 (s, 1 H), 7.74 (s, 1 H), 4.49–4.44 (q, J = 7.2 Hz, 2 H,
CH ), 1.46–1.42 (t, J = 7.0 Hz, 3 H, CH ).
2
3
1
3
C NMR (100 MHz, CDCl ): d = 163.6, 150.0, 149.8, 147.6, 144.0,
3
1
43.4, 131.7, 127.3, 109.3, 97.4, 62.4, 60.9, 14.2.
LCMS: m/z calcd 488.08; found: 488.00.
Anal. Calcd for C H BrIN O : C, 34.61; H, 2.27; N, 14.35. Found:
14
11
5
2
C, 34.61; H, 2.21; N, 14.48.
20) Holland, J. M.; McAllister, J. A.; Lu, Z.; Kilner, C. A.;
Thornton-Pett, M.; Halcrow, M. A. Chem. Commun. 2001,
557.
Acknowledgment
(
21) Schubert, U. S. In Tailored Polymers & Applications;
Yagci, M. Y.; Nuyken, O.; Ito, K.; Wnek, G., Eds.; VSP
Publishers: Utrecht, 2000, 63–85.
(22) Lohmeijer, B. G. G.; Schubert, U. S. Macromol. Chem.
Phys. 2003, 204, 1072.
(23) Ziessel, R. Synthesis 1999, 1839.
We are grateful to DST (Fast Track Scheme No. SR/FTP/CS-115/
007), Govt. of India, School of chemistry and University of Hy-
derabad (UoH), India for financial support. S.B. and P.H. thank the
CSIR for Junior Resarch Fellowships. We thank Mr. Srinivasa Rao
Lanke for his initial synthetic work.
2
(
24) Miyaura, N.; Suzuki, A. Chem. Commun. 1979, 866.
(
25) Sonoashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
References
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(
(
26) Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636.
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