One-Pot Sequential Bromination and Fluorination to Access 3-Fluoroimidazo[1,2-a]pyridines from Arylketones

Article abstract of DOI:10.1002/ejoc.201800578

3-Fluoro-2-arylimidazo[1,2-a]pyridines were selectively synthesised in one-pot from acetophenones and 2-aminopyridines under mild conditions. The sequence of reactions involved bromination, condensation, and late-stage fluorination. Two halogenating reagents play key roles in the process. We found that tetrabutylammonium tribromide and Selectfluor^TM gave excellent yields of the desired products in the one-pot sequential reaction.

Full text of DOI:10.1002/ejoc.201800578

A Journal of
Accepted Article
Title: One-pot Sequential Bromiation and Fluorination to Access 3-
Fluoroimidazo[1, 2-a]pyridines from Arylketones
Authors: Sandip Sopanrao Shinde, Rohini Udavant, and Ashok Yadav
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800578
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European Journal of Organic Chemistry
10.1002/ejoc.201800578
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One-pot Sequential Bromination and Fluorination to Access 3-
Fluoroimidazo[1, 2-a]pyridines from Arylketones
Rohini N. Udavant, Ashok R. Yadav, and Sandip S. Shinde,*
Dedication ((optional))
Abstract: Selectively 3-Fluoro-2-arylimidazo[1,2-a]pyridines were
synthesized in one-pot from acetophenones, and 2-aminopyridines
under mild condition is described. The sequential reactions involved
bromination, condensation and late-stage fluorination in the
presence of two halogenating reagents are play key role in the
reaction. It is found that the tertabutyalammonium bromide and
aminopyridine under mild conditions. Our particular interest in
establishing new fluorination methods.14
TM
Selectfluor reagents are uninterrupted in sequentially reaction to
afford the excellent yield of desire product compare to other
halogenating agents.
Figure 1. Structures of bioactive compounds and imaging agents
based on imidazopyridines
Herein, we report the sequential one-pot direct synthesis of 3-F-
IMPY derivatives using arylketones and various 2-
aminopyridines in the presence of two halogenation reagents
Introduction
TBABr
3
and SelectfluorTM in one-pot.
The number of pharmaceutical drugs and agrochemicals contain
the imidazo[1,2-a]pyridine (IMPY) scaffold,1 such as drug
molecule Zolpidem
GSK812397 drug. The radio-ligand I-IMPY for Single Photon
a
hypnotic agent,2
and anti-HIV
Results and Discussion
3
125
4
Emission Computed Tomography (SPECT) and fluorine labelled
Initially, the screening of bromination reagents to generate
phenacyl bromide from aceophenone under various solvents to
assess the uninterrupted cyclization with 2-aminopyridine (3) to
give IMPY and finally fluorination using SelectfluorTM under
sequential conditions were performed in one-pot as shown in
Table 1. Acetophenone (1) treated with tertabutyalammonium
bromide (TBAB) in tert-amyl alcohol (t-AmylOH) at room
IMPY analogues FPM-IMPY or FEM-IMPY (Fig 1) were utilized
to trace the Aβ-amyloid of Alzheimer’s diseases using Positron
Emission Tomography (PET).5
Various methods have been developed for the synthesis of
IMPY by following traditional stepwise reactions of arylketone
with halogens to form α-haloarylketones, followed by
condensation with 2-aminopyridine in the presence of base
temperature and reaction progress
was monitor on TLC
6
catalyst. A wide range of brominating reagents have been
analysis, reaction didn’t proceed at all (entry 1). The same
reaction performed using NBS showed formation of some
phenacyl bromide (2). Subsequently, added 3 in the same
utilized for α-bromination, including N-bromosuccinimide (NBS),
NaOBr, Br
2
,
CuBr
2
8
,
CBrCl
The synthesis of regioselectivity
3
,7 and tertabutyalammonium
tribromide (TBATB).
1
reaction pot and continued at 80 °C for 2h. The H NMR anaylsis
halogenated-IMPY is still in its infancy because the
monohalogen cannot be maintained on the 3-position of IMPY
as long as α-haloarylketones are used for condensation with
of reaction mixture confirmed the formation of some 2-phenyl-
imidazo[1, 2-a]pyridine (4). The further treatment of SelectfluorTM
(
2
equiv) on same reaction mixture gave the desire
9
aminopyridine. To the based on our litrature survey, there is
regioselective monofluorinated 5 in only 37% yield, along with a
trace amount of 3,3-difluoro-2-phenyl-2,3-dihydroimidazo[1,2-
a]pyridine-2-ol (6) (entry 2). Interestingly, the use of TBATB
only one report for the selective 3-fluorination on IMPY scaffold
by Sun et al.10 The reaction generally utilized stoichiometric or
catalytic quantity of single halogen source either fluorine,
bromine or iodine for α-halogenation of ketone and same
halogen were incorparated on imidazopyridines scaffold after
condesation.11 Among the haloganes, the fluorinated
heterocyclics are significantly improtant due to the unique
physicochemical properties of fluorine.12 However, the
fluorination methods have some limitations in terms of its
selectivity, sensitivity and formation of by-products.13 Till date
there is no efficient one-pot method for the synthesis of
instead
phenylimidazo[1,2-a]pyridine (5) was produced in 54% yield
entry 3). These results encourage us for further optimization of
of
NBS,
the
desired
product
3-fluoro-2-
(
the one-pot sequential bromination, cyclization, and fluorination
to synthesis of regioselective 3-fluoro-IMPY 5 with avoid the
formation by-product. As shown in entry 4, the addition of H
2
O
along with SelectfluorTM, significantly increased the formation of
5
.
Similar reactions were performed in a combination of water
and t-amyl alcohol, but the selectivity of 5 did not improve
entries 5-6).
henceforth mentioned scoffold from
arylketone and
(
Noteworthy, the excess addition of 2-aminopyridine after the
condensation provided 5 in a very high yield (88%, entry 7)
along with trace amount of undesired 6. The second
fluorination was also suppressed in the presence of 3, due to it
acts as a base that rapidly eliminates the acidic proton to
provide a significant amount of 5.
[
a]
Division of Organic Chemistry, National Chemical Laboratory (CSIR-
NCL), Dr. Homi Bhabha Road, Pashan, Pune 411008, India.
E-mail: ss.shinde@ncl.res.in
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Table 1. One-pot synthesis of 3-fluoro-2-phenylimidazo[1, 2-a]pyridine from
acetophenone.
benzenedisulfonimide
Fluorobenzenesulfonimide (NFSI)
SelectfluorTM as illustrated in figure 2. The fluorination step with
(NFOBS),
and
N-
a
was compared with
TM
intermediate IMPY in the presence of Selectfluor proceeded
much faster than that of other reagents, due to the highly
oxidising ability of SelectfluorTM in reaction.
Yield
Br-source Solvent (15
2
H O
Entry
of
5
Comments
(1 equiv)
mL)
(L)
c
(%)
1
2
3
4
5
TBAB
NBS
t-amylOH
t-amylOH
t-amylOH
t-amylOH
-
-
0
d
-
37
54
78
trace of 6
TBATB
TBATB
TBATB
-
18% of 6
7% of 6
200
5 mL
d
trace
24% of 6
t-amylOH
6
TBATB
1 mL
62
13% of 6
(4 mL)
b
7
TBATB
TBATB
TBATB
TBATB
TBATB
t-amylOH
n-pentanol
t-BuOH
200
200
200
200
88
18
76
40
13
b
d
8
trace of 7
b
9
b
d
10
DMSO
trace of 6
Table 2. Scope of 2-aminopyridines
b
11
1,4-dioxane 200
Table 2 shows the results for the one-pot formation of F-IMPY
under optimized condition (entry 7, table 1) in attention to the
scope, and limitation of our one-pot strategy with a variety of
substituted 3, as shown in Table 2. The phenacyl bromide with
electron-rich methyl groups on 3 at the para- and ortho positions
proceeded smoothly and converted to corresponding
a
All reactions performed acetophenone (2.0 mmol), bromine source, and 2-
TM
O/solvent.b
aminopyridine (1.1 mmol), and Selectfluor
Excess 2-aminopyrdine (2.3 mmol) used. cIsolated yield. Determined by 1H-
NMR.
(2.0 mmol) in H
2
d
Changing the reaction solvents to tert-BuOH, n-pentanol, DMSO,
and dioxane did not increase the selectivity of desired 5 but
instead favored the formation of the additional by-products 6 and
intermediate 4a-b in high yield. After cooling to room
TM
2
temperature, fluorination with Selectfluor in H O gave almost
quantitative yield (88-90%) of mono-fluorinated imidazopyridine
derivatives 5a-d. Reaction with the halogen substituted 3c-d
substrates afforded the desired product 5c-d in reasonable yield.
In the next stage, various arylketones and 2-aminopyridines
investigated in the sequential one-pot process. The results
depicted in Table 3. Various arylketones bearing methoxy-, nitro-,
chloro- groups were treated with TBATB in t-amyl alcohol and
reacted with substituted 3 bearing methyl and chloro groups to
afford 5e-o in reasonable moderate to good yield (54-91%).
Reactions with heterocyclic ketone provided corresponding 3-
fluoro-2-thiophenyl-IMPY (5p) in 78% yield. (entry 12). We afford
the poor yield of 3-Fluoro-IMPY 5q-r when used the aliphatic
ketones as substrates for brominaton (entries 13-14), may due
to the low reactivity of substrates. Substitution of electron
withdrawing groups on arylketones (entries 4 and 10) gave low
yields of the desired fluorinated-products. The sequential one-
pot protocol is highly versatile, and selectively provided the
mono-fluorinated imidazopyridine derivatives with various
substituents.
7
(entries 8-11). Overall, 5 was smoothly obtained in a one-pot
process by sequential bromination using TBATB and cyclization
and late-stage fluorination using SelectfluorTM in tert-amyl
alcohol/H O, where 3 not only is the condensing partner but play
2
role of a base.
Figure 2. Effect of the various electrophilic fluorinating agents in one-pot
conidition.
Based on overall observation a plausible mechanism proposed
in scheme 1. The bromination of arylketone was using by
TBATB to from bromo acetophenone A. In this intermedate A
We attempt various electrophilic fluorinating agents to improve
the yield of product with regioselectivity in one-pot conditions.
8
bromine is more labile which can be displacing by nitrogen of
The
reactivity
of
fluorinating
agents
N-Fluoro-o-
pyridine ring which gives the intermedate B. The lone pair of
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amine of B promotes the cyclization and aromatization yields
IMPY.9 The electrophilic fluorination of electron rich
aminopyridine completes the aromatization to provide the
desired 3-fluorinated product D.
2
imidazopyridines occurs at the 3-position of C, H O reacts with
the cation and the in situ abstraction of the hydrogen by 2-
Table 3. One-pot synthesis of various 3-fluoro-IMPY from various 1 and 3.[a]
[
b]
Entry
Arylketone
2-Aminopyridine
3-F-IMPY analogs
Yield (%)
3
76
81
88
63
1
2
3
4
3
3
3
3
b
91
67
90
5
6
7
3
a
3b
3
b
d
54
77
8
9
3
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3b
69
10
8
7
2
9
8
4
1
1
1
1
2
3
3
3
3
35
14
[
a] All reactions carried out according to entry 7 of Table 1. [b] Isolated yield.
Experimental Section
General procedure for the preparation of 3-fluoro-imidazo[1,2-a]pyridine.
3
-Fluoro-2-phenylimidazo[1, 2-a]pyridine (5):10 In a round bottom flask,
solution of acetophenone (250 mg, 2.00 mmol, 1.0 equiv.) and TBATB
1.0g, 2.10 mmol, 1.01 equiv) in 15mL tert-amyl alcohol was stirred at
(
room temperature and progress of reaction was monitored by TLC. After
completion, 2-aminopyridine (218.46 mg, 2.32 mmol, 2.1 equiv.) added in
reaction mixture and stirred at 80 °C for 2h. Upon completion on TLC
analysis, the reaction mixture was cooled at rt then H O (200 L, 11.0
2
mmol ) and SelectfluorTM (766.63 mg, 2.16 mmol, 2.0 equiv) was added
and reaction completion analyzed on TLC. After completion, was diluted
with saturated solution of Na
The combined organic layers dried over anhydrous Na
2
CO
3
and extracted with EtOAc (10 mL × 3).
SO , evaporated
Scheme 1. Proposed reaction mechanism.
2
4
under vacuum, and the crude product purified by column
1
chromatography (50% EtOAc/petroleum ether) to afford title product 5. H
NMR (CDCl
1
7
3
, 400 MHz): δ 8.03 (d, J = 8.0 Hz, 2H), 7.93 (d, J = 6.5 Hz,
H), 7.56 (d, J = 9.2 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.38-7.31 (m, 1H),
.16 (dd, J = 7.4, 8.6 Hz, 1H), 6.86 (t, J = 6.9 Hz, 1H); 13C NMR (CDCl3,
Conclusions
In conclusion, we have established an efficient one-pot
regioselective method for the synthesis of 3-fluoro-2-
phenylimidazo[1,2-a]pyridine from general arylketones and 2-
aminopyridines in protic media. Arylketones bearing a wide
range of functional groups tolerated to obtain the corresponding
100 MHz): δ 138.6 (d, J = 274.6 Hz), 136.9 (d, J = 5.72 Hz), 131.5 (d, J
= 5.0 Hz), 128.7, 127.8, 126.3 (d, J = 3.8 Hz), 123.9, 122.6, 120.4, 117.9,
112.6; 19F NMR (CDCl
, 376 MHz): δ -154.89; HRMS-ESI (m/z): calcd
[M+ H] 213.0828, found 213.0824.
3
+
for C13
H
10FN
2
3
4
3
-Fluoro-6-methyl-2-phenylimidazo[1,2-a]pyridine (5a)10: 1H NMR (CDCl
,
3
00 MHz): δ 8.00 (d, J = 7.3 Hz, 2H), 7.70 (s, 1H), 7.46 (t, J = 7.6 Hz,
H), 7.32 (t, J = 7.3 Hz, 1H), 6.99 (d, J = 9.2 Hz, 1H), 2.35 (s, 3H); 13C
3
-fluoro-imidazopyridine derivatives in good to excellent yields.
This method not require additional base because the dual role of
-aminopyridine as reactant and base. The fluorination is the
2
NMR (CDCl3, 100 MHz): δ 138.3 (d, J = 274.6 Hz), 135.9 (d, J = 5.72 Hz),
31.4 (d, J = 4.7 Hz), 128.7, 127.7, 127.5, 126.1 (d, J = 4.7 Hz), 122.7,
key step to rapid access the chemo- and regio-selective 3-F-
IMPY scaffolds.
1
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1
22.2, 117.9, 117.0, 18.3; 19F NMR (CDCl
3
, 376 MHz): δ -154.75; HRMS-
2-([1,1’-Biphenyl]-4-yl)-3-fluoro-8-methylimidazo[1,2-a]pyridine (5i): 1H
NMR (CDCl , 400 MHz): δ 8.13 (d, J = 7.9 Hz, 2 H), 7.81 (d, J = 6.7 Hz, 1
3
+
ESI (m/z): calcd for C14
H12FN
2
[ M + H] 227.0985, found 227.0987.
H), 7.73 (d, J = 7.9 Hz, 2 H), 7.68 (d, J = 7.9 Hz, 2 H), 7.48 (t, J = 7.6 Hz,
2 H), 7.41 - 7.34 (m, 1 H), 6.95 (d, J = 6.7 Hz, 1 H), 6.77 (t, J = 6.7 Hz, 1
H), 2.65 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ 141.1, 140.5, 139.2(d, J =
-Fluoro-8-methyl-2-phenylimidazo[1,2-a]pyridine (5b)10
CDCl 400 MHz): δ 8.04 (d, J = 7.9 Hz, 2H), 7.80 (d, J = 6.7 Hz, 1H),
1H NMR
3
(
:
3
,
2
75. 9 Hz) 137.6(d, J = 5.4 Hz), 131.3(d, J = 5.4 Hz), 129.1, 128.1, 127.6
7
6
.48 (t, J = 7.9 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 6.95 (d, J = 6.7 Hz, 1H),
.77 (t, J = 6.7 Hz, 1H), 2.63 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 138.8
(d, J = 4.6 Hz), 127.3, 127.0 (d, J = 4.6 Hz), 122.7, 122.1, 118.6, 113.0,
7
7.6, 77.5, 77.3, 16.6; 19F NMR (CDCl
3
, 376 MHz): δ -153.91; HRMS-ESI
[M + H] 302.1298, found 302.1300.
(
d, J = 275.1 Hz), 137.1 (d, J = 4.6 Hz), 131.6 (d, J = 5.4 Hz), 130.0,
+
1
28.7, 128.5, 127.7, 126.4 (d, J = 3.8 Hz), 122.8, 118.3, 112.8, 16.3; 19F
(m/z): calcd for C20
H16FN
2
NMR (CDCl
3
,
376 MHz):
δ
-154.32; HRMS-ESI (m/z)
:
calcd for
+
2-(4-Chlorophenyl)-3-fluoro-6-methylimidazo[1,2-a]pyridine (5j): 1H NMR
CDCl , 400 MHz): δ 7.90-7.83 (m, J = 7.9 Hz, 2H), 7.71 (s, 1H), 7.54 (d,
J = 9.2 Hz, 1H), 7.43-7.39 (m, J = 8.5 Hz, 2H), 7.06 (d, J = 9.2Hz, 1H),
.36 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 138.2 (d, J= 273.70 Hz),
136.3 (d, J = 4.7 Hz), 133.6, 131.4, 128.8, 128.2, 127.7 (d, J = 3.8 Hz),
23.2, 121.3, 117.9, 117.0, 18.2; 19F NMR (CDCl
, 376 MHz): δ -154.77;
[M+ H]+ 261.0595, found
C
14
H
12FN
2
[M + H] 227.0985, found 227.0982.
(
3
-Bromo-3-fluoro-2-phenylimidazo[1,2-a]pyridine (5c)10 : 1H NMR (CDCl
3
,
00 MHz): δ 8.05 (br. s. , 1H), 7.98 (d, J = 7.6 Hz, 2H), 7.51-7.40 (m,
H), 7.38-7.32 (m, 1H), 7.19 (d, J = 9.5 Hz, 1H); 13C NMR (CDCl3, 100
6
4
3
2
1
3
MHz): δ 138.2 (d, J = 277.5 Hz), 135.2 (d, J = 5.7 Hz), 130.9 (d, J = 3.8
Hz), 128.8, 128.1, 127.5, 126.3 (d, J = 3.8 Hz), 123.6, 120.4, 118.5,
HRMS-ESI (m/z): calcd for
261.0599.
14 2
C H11ClFN
07.6; 19F NMR (CDCl
1
3
, 376 MHz): δ -153.04; HRMS-ESI (m/z): calcd for
+
C
13
H
9
BrFN
2
[M+ H] 290.9933, found 290.9930.
3
-Fluoro-2-(3-methoxyphenyl)-8-methylimidazo[1,2-a]pyridine(5k):
1H
3
, 400 MHz): δ 7.76 (d, J = 6.7 Hz, 1H), 7.65-7.58 (m, 2H),
-Chloro-3-fluoro-2-phenylimidazo[1,2-a]pyridine (5d)10
CDCl , 400 MHz): δ 8.04-7.91 (m, 3H), 7.47 (t, J = 7.8 Hz, 3H), 7.39-
3
1H NMR
NMR (CDCl
6
(
:
7
.38 (t, J = 8.2 Hz, 1H), 6.96-6.84 (m, 2H), 6.73 (t, J = 6.7 Hz, 1H), 3.91
(s, 3H), 2.62 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 159.9, 138.9 (d, J =
.32 (m, 1H), 7.11 (d, J = 9.5 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ
38.4 (d, J = 277.0 Hz), 135.1 (d, J = 5.7 Hz), 131.0 (d, J = 3.8 Hz),
28.7, 128.1, 126.2 (d, J = 3.8 Hz), 125.3, 123.9, 121.2, 118.2, 118.1;
7
1
1
2
1
75.6 Hz), 137.1 (d, J = 5.7 Hz), 133.2 (d, J = 4.7 Hz), 129.6, 127.8,
22.3, 121.9, 118.8 (d, J = 4.7 Hz), 118.2, 113.6, 112.6, 111.4 (d, J = 3.8
1
9
1
9F NMR (CDCl
Hz), 55.2, 16.1; F NMR (CDCl
calcd for C15
3
, 376 MHz): δ -153.73; HRMS-ESI (m/z):
O [M + H] 257.1090, found 257.1092.
3
, 376 MHz ): δ -153.01; HRMS-ESI (m/z): calcd for
+
+
H
14FN
2
C
13
H
9
ClFN
2
[M+ H] 247.0438, found 247.0441.
2-(4-Chlorophenyl)-3-fluoro-8-methylimidazo[1,2-a]pyridine (5l) : 1
CDCl , 400 MHz): δ 7.95-7.88 (m, J = 8.5 Hz, 2H), 7.69 (d, J = 6.7 Hz,
1H), 7.42-7.36 (m, J = 7.9 Hz, 2H), 6.89 (d, J = 6.7 Hz, 1H), 6.70 (t, J =
H NMR
-(4-Chlorophenyl)-3-fluoroimidazo[1,2-a]pyridine (5e)10 : 1H NMR (CDCl
3
,
2
(
3
4
00 MHz): δ 7.98-7.89 (m, 3H), 7.55 (d, J = 9.2 Hz, 1H), 7.44 (d, J = 8.5
Hz, 2H), 7.21-7.13 (m, 1H), 6.88 (t, J = 6.7 Hz, 1H); 13C NMR (CDCl3, 100
6
2
.7 Hz, 1H), 2.58 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 138.7 (d, J =
75.6 Hz), 137.1 (d, J = 5.7 Hz), 133.0, 130.4 (d, J = 4.7 Hz), 128.7,
MHz): δ 138.5 (d, J = 275.1 Hz), 137.0 (d, J = 6.1 Hz), 133.6, 131.3,
1
1
30.0 (d, J = 6.1 Hz), 128.9, 127.5 (d, J = 3.8 Hz), 124.2, 121.6, 120.4,
127.7, 127.3 (d, J = 3.8 Hz), 122.4, 120.8, 118.1, 112.6, 16.0; 19F NMR
17.8, 112.9; 19F NMR (CDCl
3
, 376 MHz): δ -154.46; HRMS-ESI (m/z):
[M + H] 247.0438, found 247.0436.
+
(CDCl
3
, 376 MHz): δ -153.63; HRMS-ESI ( m/z): calcd for C14
H
11ClFN
2
calcd for C13
H ClFN
9
2
+
[M + H] 261.0595, found 261.0593.
3
-Fluoro-2-(3-methoxyphenyl)imidazo[1,2-a]pyridine (5f)
:
1H NMR
6
-Chloro-3-fluoro-2-(3-methoxyphenyl)imidazo[1,2-a]pyridine (5m): 1H
, 400 MHz): δ 7.96 (s, 1H), 7.56 (br.s., 2H), 7.49 (d, J = 9.2
Hz, 1H), 7.38 (t, J = 7.9 Hz, 1H), 7.14-7.08 (m, 1H), 6.94-6.87 (m, 1H),
.90 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 160.0, 138.5 (d, J = 278.4
(
7
3
CDCl , 400 MHz): δ 8.01 (br.s., 1H), 7.72 (br.s., 1H), 7.59 (br.s., 2H),
.43 (br.s., 1H), 7.32 (br.s., 1H), 7.08-6.86 (m, 2H), 3.95 (br.s., 3H); 13C
NMR (CDCl
3
NMR (CDCl3, 100 MHz): δ 160.0, 138.5 (d, J = 274.3 Hz), 137.0 (d, J =
3
5
1
.4 Hz), 129.8, 124.4, 122.5, 120.5, 119.04 (d, J = 3.8 Hz), 117.8, 114.3,
13.0, 111.4, 55.4; 19F NMR (CDCl
Hz); 135.1 (d, J = 5.7 Hz); 132.5 (d, J = 4.7 Hz); 129.8, 125.3, 123.9,
121.2, 118.8 (d, J = 4.7 Hz); 118.3, 118.2, 114.3, 111.2 (d, J = 2.8 Hz),
3
, 376 MHz): δ -154.78; HRMS-ESI
O [M + H] 243.0934, found 243.0938.
+
(m/z): calcd for C14
H12FN
2
5
5.3; 19F NMR (CDCl
, 376 MHz): δ -152.49; HRMS-ESI (m/z): calcd for
3
+
14 2
C H11ClFN O [M + H] 277.0544, found 277.0548.
2-[(1,1’-Biphenyl]-4-yl) -3-fluoroimidazo[1,2-a]pyridine (5g)
:
1H NMR
(
CDCl
3
, 400 MHz): δ 8.13 - 8.07 (m, J = 8.0 Hz, 2 H), 7.90 (d, J = 6.5 Hz,
3
(
-Fluoro-8-methyl-2-(3-nitrophenyl)imidazo[1,2-a]pyridine (5n): 1H NMR
CDCl , 400 MHz): δ 8.87 (s, 1 H), 8.35 (d, J = 7.3 Hz, 1 H), 8.16 (d, J =
6.7 Hz, 1 H), 7.82 (d, J = 6.1 Hz, 1 H), 7.66 - 7.60 (m, 1 H), 6.99 (d, J =
.7 Hz, 1 H), 6.85 - 6.78 (m, 1 H), 2.63 (s, 3 H); 13C NMR (CDCl3,100
1
=
(
H), 7.76 - 7.70 (m, J = 8.4 Hz, 2 H), 7.67 (d, J = 7.2 Hz, 2 H), 7.56 (d, J
9.2 Hz, 1 H), 7.47 (t, J = 7.6 Hz, 2 H), 7.40 - 7.34 (m, 1 H), 7.18 - 7.11
3
m, 1 H), 6.84 (t, J = 6.9 Hz, 1 H);13C NMR (CDCl3,100 MHz): δ 140.5,
6
1
40.3, 138.6 (d, J = 275. 9 Hz), 136.9 (d, J = 6.1 Hz), 130.4 (d, J = 5.4
MHz): δ 148.7, 139.3 (d, J = 277.4 Hz), 137.5 (d, J = 5.39 Hz), 133.8 (d,
J = 5.39 Hz), 131.9 (d, J = 3.85 Hz), 129.6, 128.2, 123.1, 122.1, 121.0 (d,
Hz), 128.7, 127.3, 126.9, 126.6 (d, J = 3.8 Hz), 123.9, 122.3, 120.3,
17.7, 112.6; 19F NMR (CDCl
1
3
, 376 MHz): δ -154.55; HRMS-ESI (m/z):
[M + H] 289.1141, found 289.1137.
J = 4.62 Hz), 119.8, 118.4, 113.2, 16.1; 19F NMR (CDCl
52.31; HRMS-ESI (m/z): calcd for C14
[M + H]+ 272.0835,
found 272.0837.
+
3
, 376 MHz): δ -
calcd for C19
H14FN
2
1
3 2
H11FN O
3
4
-Fluoro-2-(3-nitrophenyl)imidazo[1,2-a]pyridine (5h)10 : 1H NMR (CDCl
00 MHz): δ 8.84 (s, 1 H), 8.34 (d, J = 7.9 Hz, 1 H), 8.18 (d, J = 6.7 Hz, 1
3
,
2
-([1,1’-Biphenyl]-4-yl)-3-fluoro-7-methylimidazo[1,2-a]pyridine (5o): 1H
NMR (CDCl , 400 MHz): δ 8.08 (d, J = 7.9 Hz, 2H), 7.81 (d, J = 6.7 Hz,
H), 7.72 (d, J = 7.9 Hz, 2H), 7.67 (d, J = 7.9 Hz, 2H), 7.47 (t, J = 7.3 Hz,
H), 7.40 - 7.30 (m, 2H), 6.70 (d, J = 6.7 Hz, 1H), 2.41 (s, 3H); 13C NMR
H), 7.98 (d, J = 6.7 Hz, 1 H), 7.68 - 7.56 (m, 2 H), 7.26 - 7.21 (m, 1 H),
.94 (t, J = 7.0 Hz, 1 H); 13C NMR (CDCl3,100 MHz): δ 148.8, 139.0 (d, J
277.5 Hz), 137.2 (d, J = 5.72 Hz), 133.4 (d, J = 2.86 Hz), 131.9 (d, J =
.86 Hz), 129.7, 124.8, 122.4, 121.1 (d, J = 4.77 Hz), 120.7, 120.5, 118.1,
3
6
=
2
1
1
2
13.3; 19F NMR (CDCl
(CDCl3,100 MHz): δ 140.7, 140.2, 138.5 (d, J = 275.1 Hz), 137.3(d, J =
5.4 Hz),135.1, 130.5 (d, J = 5.4 Hz), 128.8, 127.3, 126.9, 126.5, 126.5 (d,
3
, 376 MHz): δ -153.06; HRMS-ESI (m/z): calcd for
+
C H FN O
13 9 3 2
[M + H] 258.0679, found 258.0681.
J = 3.8 Hz), 121.5, 119.6, 115.9, 115.4, 21.4; 19F NMR (CDCl
3
, 376
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MHz):
δ
-155.27; HRMS-ESI (m/z): calcd for C20
H
16FN
2
[M
+
H]+
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Entry for the Table of Contents (Please choose one layout)
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Rohini N. Udavant, Ashok R. Yadav, and
Sandip S. Shinde,*
Page No. – Page No.
One-pot Sequential Bromination and
Fluorination to Access 3-
Fluoroimidazo[1, 2-a]pyridines from
Arylketones
3
-Fluoro-2-arylimidazo[1,2-a]pyridines were synthesized in one-pot from
acetophenones, and 2-aminopyridines under mild condition is described.
[
a]
Division of Organic Chemistry, National Chemical Laborator
NCL), Dr. Homi Bhabha Road, Pashan, Pune 411008, India
E-mail: ss.shinde@ncl.res.in
Supporting information for this article is given via a link at the
the document.((Please delete this text if not appropriate))
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