Visible light induced tetramethylethylenediamine assisted formylation of imidazopyridines

Article abstract of DOI:10.1039/c8ob00532j

A metal-free visible light induced C-3 formylation of imidazo[1,2-a]pyridine has been developed using tetramethylethylenediamine (TMEDA) as a one carbon source. An array of 3-formyl imidazo[1,2-a]pyridines with wide functionality are synthesized using rose bengal as a photosensitizer under ambient air.

Full text of DOI:10.1039/c8ob00532j

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Visible light induced tetramethylethylenediamine assisted
formylation of imidazopyridines
Golam Kibriya,a Avik K. Bagdi,b and Alakananda Hajra*a
Received 00th January 20xx,
Accepted 00th January 20xx
A
metal‐free visible light induced C‐3 formylation of imidazo[1,2‐a]pyridine has been developed using
tetramethylethylenediamine (TMEDA) as one carbon source . An array of 3‐formyl imidazo[1,2‐a]pyridines with wide
functionality are synthesized using rose bengal as photosensitizer under ambient air.
DOI: 10.1039/x0xx00000x
www.rsc.org/
a
scope limited their practical applicability.8 Visible light‐
promoted photoredox catalysis has also been employed for
the functionalization such as thiolation, azolylation,
cyanomethylation etc. of imidazo[1,2‐a]pyridines.9 Recently,
we have also reported C‐3 alkoxylation and thiocyanation of
imidazopyridine via visible light photoredox catalysis.10 In
continuation of our interest in the synthesis and
functionalization of imidazo[1,2‐a]pyridines; herein we report
Introduction
Visible light induced photocatalysis has gained much
interest of the synthetic chemists due to its practical
applicability and use of inexpensive energy source.1 As a
consequence it has emerged as an alternative to the transition
metal catalysis and traditional radical pathway for C‐H
functionalization.2 Although different ruthenium and iridium‐
complexes are successfully employed for the photocatalysis,
high cost and potential toxicity of these metal‐based
photocatalysts limited their practical applicability.3 In the past
few years, the uses of organic dyes as photosensitizer have
increased tremendously. These are environmentally benign,
inexpensive and easy to handle.4
a
visible light induced C‐3 formylation of imidazo[1,2‐
a]pyridines using rose bengal as a photosensitizer and TMEDA
as one carbon source under aerobic conditions (Scheme 1).
Imidazo[1,2‐a]pyridine has gained interest of chemists over
the years due to its wide applications in pharamaceuticals and
material sciences.5 A number of efficient methodologies have
been developed for the synthesis and functionalization of
imidazo[1,2‐a]pyridines.6 As the pharmaceutical activities are
dependent on the nature of the functionalities at C‐3
positions, various methodologies have been developed for the
C‐3 functionalization of the imidazo[1,2‐a]pyridines using
different strategies. Formylated heterocycles are very
important scaffolds as they are often used as synthetic
intermediate for the synthesis of complex molecule. So, a
number of strategies has been developed for the formylation
of heterocycles.7 Recently, Li et al. reported a new strategy for
the formylation of indoles via photoredox catalysis.7f Although
there are few reports for the C‐3 formylation of imidazo[1,2‐
a]pyridines; the use of high temperature and narrow substrate
Scheme 1 Formylation of imidazopyridines
Results and discussion
We began our investigation by taking 2‐phenylimidazo[1,2‐
a]pyridine (1a) as the model substrate for the formylation of
imidazopyridine using TMEDA (
2). Initially we carried out the
reaction using equiv TMEDA, rose bengal as
2
a
photosensitizer and 4 equiv KI as additive in MeCN‐H2O (5:1)
under 20 W white LED light. Gratifyingly, the expected 2‐
phenylimidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
3a)
was
obtained with 62% yield after 36 h (Table 1, entry 1). Inspired
by this initial result, we screened various solvents like DMSO,
DMF, 1,2‐DCE, DCM, EtOH, toluene, THF, and H2O (Table 1,
entries 2‐10). Among these 1,4‐dioxane was the best one
affording 81% of the desired product (Table 1, entry 9). Other
photocatalysts such as eosin Y, Ru(bpy)3Cl2•6H2O and Ir(ppy)3
were also tested, but none of them was so effective like rose
bengal (Table 1, entries 11‐13). The reaction yield decreased
significantly with decreasing the loading of TMEDA (Table 1,
entries 14 and 15). Other one carbon sources like DMEDA,
HMTA, N,N‐dimethyl aniline, N‐methyl aniline etc. were also
investigated but no formation of the product was observed in
these cases (Table 1, entries 16‐19). Use of I2, TBAI and NH4I as
a. Department of Chemistry, Visva‐Bharati (A Central University), Santiniketan
731235, India, Email: alakananda.hajra@visva-bharati.ac.in
.
b. Department of Chemistry, TDB College, Raniganj, Paschim Bardhaman 713347,
India.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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additives instead of KI was not effective (Table 1, entries 20‐
(3h and 3i). Hydroxy‐substituted imidazo[1,2‐a]pyridine also
22). No product was formed in the absence of any furnished the formylated product with good yield (3j).
photocatalyst (Table 1, entry 23). In addition formation of Interestingly, marketed drug zolimidine was also formylated
product did not take place in dark as well as under argon under the present reaction conditions with 86% yield (3k). To
atmosphere (Table 1, entries 24 and 25). These results indicate our delight, the naphthyl and thiophene substituted
that the reaction is a visible‐light promoted reaction and imidazo[1,2‐a]pyridines
afforded
the
corresponding
aerobic oxygen is necessary. Thus the optimized reaction formylated products with high yields (3l
‐
3n). In addition,
conditions was obtained using 2 mol % rose bengal and 4 equiv isobutyl and cyclopropyl substituted imidazopyridines were
KI in 1,4‐dioxane‐H2O (5:1) under irradiation with 20 W white found to be very effective for the formylation (3o and 3p).
LED bulb (380‐750 nm) for 36 h in air (Table 1, entry 9).
Interestingly, unsubstituted imidazo[1,2‐a]pyridine selectively
produced the C‐3 formylated product with excellent yield (3q).
Also, imidazo[1,2‐a]pyridines bearing methyl substituent on
pyridine ring at different positions efficiently reacted with
Table 1. Optimization of the Reaction Conditionsa
TMEDA to afford the desired products with good yields (3r‐3t).
Table 2. Scope of Substratesa
Entry
Photocatalyst
Solvent
Additi Amine Yields (%)
ve
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
I2
TBAI
NH4I
KI
KI
KI
(equiv.)
1
2
3
4
5
6
7
8
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
eosin Y
CH3CN
DMSO
DMF
1,2‐DCE
DCM
EtOH
toluene
THF
1,4‐dioxane
H2O
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
2
2
2
2
2
2
2
2
2
2
2
2
2
0.5
1
2
2
2
2
2
2
2
2
2
2
62
32
25
15
trace
46
nrb
75
81
nr
62
22
38
30
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
Ru(bpy)3Cl2·6H2O
Ir(ppy)3 (10)
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
‐
58
ndc
nrd
nde
ndf
48
trace
56
nr
nrg
nrh
rose bengal
rose bengal
a
Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol), photocatalyst (2 mol%),
solvent‐H2O (5:1, 3 mL), 20 W white LED bulb. b No reaction. c DMEDA instead of
d
e
f
2. HMTA instead of 2. N,N‐dimethyl aniline instead of 2. N‐methyl aniline
instead of 2. g In dark. h Under argon atmosphere.
aReaction conditions: 0.2 mmol of 1, 0.4 mmol of 2, rose bengal (2 mol%), and 0.8
mmol of KI in 3 mL 1,4‐dioxane:H2O (5:1) irradiated with 20 W white LED for 36 h.
c
bReaction complete in 24 h. Reaction continued for 48 h. dReaction complete in
12 h.
With the optimized reaction conditions in hand, we
investigated the scope of this formylation reaction to show the
generality of this methodology (Table 2). At first we examined
the effect of substituents in the C‐2 position of the
imidazo[1,2‐a]pyridines. Imidazopyridine moiety with electron‐
donating substituents like ‐CH3 and ‐OCH3 on the phenyl ring
afforded the corresponding formylated products with excellent
yields (3b and 3c). Halogens were also well tolerated under the
To extend the scope of our methodology, we carried out
the reaction with substituted indolizines (Table 3). To our
delight, indolizines afforded the formylated products (5a
−5b)
with excellent yields under the optimized reaction conditions.
present reaction conditions
(3d‐3g). Strong electron‐
withdrawing groups like –CN and –CF3 in phenyl ring also
successfully gave the desired products without any difficulties
2 | J. Name., 2012, 00, 1‐3
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Table 3: Substrate Scope of Indolizinesa
energy to the ground‐state oxygen (3O2) forming the singlet
oxygen (1O2) which helps to form iodine radical from iodide.
Subsequently, TMEDA is oxidised to the radical cation
presence of iodine radical. The intermediate gives up a
hydrogen atom, presumably to the superoxide radical anion to
form iminium ion . Electrophilic addition of iminium ion to
2‐phenylimidazo[1,2‐a]pyridine (1a) affords imidazolenium ion
. Upon rearomatization, C‐3 substituted 2‐phenylimidazo[1,2‐
A in
A
B
B
C
a]pyridine intermediate
more facile to form iminium ion than TMEDA, intermediate
is further oxidized by iodine to generate iminium ion
D
is formed. As the intermediate
D
is
D
E
. Finally
aReaction conditions: 0.2 mmol of 4, 0.4 mmol of 2, rose bengal (2 mol%), and 0.8
mmol of KI in 3 mL 1,4‐dioxane:H2O (5:1) irradiated with 20 W white LED for 36 h.
bIsolated yield. Unless otherwise mentioned.
3‐formyl imidazo[1,2‐a]pyridine
(
3a
)
is formed by the
hydrolysis of intermediate
E
.
N
HN
The gram‐scale reaction of the present methodology was
also performed in the usual laboratory setup by taking 2‐
F
CHO
Ph
H2O
3O2
N
RB*
N
phenylimidazo[1,2‐a]pyridine (1a) and TMEDA (
2) on 6 mmol
Ph
N
3a
scale (Scheme 2). 2‐Phenylimidazo[1,2‐a]pyridine‐3‐
h
N
E
N
1O2
N
carbaldehyde (3a) was obtained without a significant decrease
in yield which implies the practical applicability of this
methodology.
I
RB
I
N
N
[O]
2
Ph
I2
O2
N
I
N
N
D
N
N
N
A
-H
N
Scheme 2: Gram‐Scale Reaction
Ph
N
Cl
O
RB
N
Cl
Cl
Cl
N
N
O2
Ph
N
C
HO2
B
Few control experiments were performed to understand
the mechanistic path for the formylation reaction of
imidazopyridines with TMEDA (Scheme 3). The reaction did not
proceed at all in the presence of radical scavenger 2,2,6,6‐
tetramethylpiperidine‐1‐oxyl (TEMPO) which signifies that the
reaction possibly proceeds through a radical pathway ( Scheme
3, eq a). Formation of product did not take place under the
argon atmosphere (Table 1, entry 25) indicating that O2 is
necessary for the reaction. In addition, when the reaction was
carried out in presence of benzoquinone (BQ) which is a
superoxide quencher,11 completely stopped the formation of
the desired product (Scheme 3, eq b ). This result suggests that
the reaction undergoes through the superoxide radical
pathway.
COONa
I
N
I
N
1a
NaO
O
I
I
Scheme 4: Proposed mechanism
Conclusions
In summary, we have developed a mild metal‐free visible‐
light driven rose bengal catalyzed C‐3 formylation of
imidazopyridines using TMEDA as one‐carbon source under
aerobic conditions. A library of 3‐formyl imidazo[1,2‐a]pyridine
derivatives with broad functionalities were synthesized at
room temperature. Most importantly, this method is scalable
and air is used as the sole green oxidant. We believe the
present visible light‐driven organophotocatalytic formylation
strategy is very convenient and practical to synthesize
N
N
standard condition
TEMPO (3 equiv.)
a)
Ph
Ph
+ TMEDA
N
N
CHO
1a
2
3a
0%
important
building
blocks
of
C‐3
formylated
imidazoheterocycles.
N
N
standard condition
BQ (3 equiv.)
Ph
Ph
b)
+ TMEDA
N
N
Experimental Section:
General Information
CHO
1a
2
3a
0%
Scheme 3: Control experiments
All reagents were purchased from commercial sources and
used without further purification. 1H NMR spectra were
determined on 400 MHz spectrometer as solutions in CDCl3.
Chemical shifts are expressed in parts per million (δ) and the
signals were reported as s (singlet), d (doublet), t (triplet), m
(multiplet), and coupling constants (J) were given in Hz. 13C{1H}
On the basis of the control experiments and literature
reports,12 a plausible mechanistic path has been outlined in
Scheme 4. The ground state of RB is converted to its excited
state RB* on absorption of visible light. RB* transfers its
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NMR spectra were recorded at 100 MHz in CDCl3 solution. 2‐(4‐Chlorophenyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
1
Chemical shifts as internal standard are referenced to CDCl3 (δ
(
3e):8g White solid (43 mg, 85%), mp: 186‐188 °C; H NMR
= 7.26 for 1H and δ = 77.16 for 13C{1H} NMR) as internal (CDCl3, 400 MHz): δ 10.03 (s, 1H), 9.65‐9.62 (m, 1H), 7.80‐7.74
standard. TLC was done on silica gel coated glass slide. All (m, 3H), 7.60‐7.56 (m, 1H), 7.52‐7.48 (m, 2H), 7.15‐7.11 (m,
solvents were dried and distilled before use. Commercially 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 179.2, 157.0, 147.8,
available solvents were freshly distilled before the reaction. All 136.3, 131.1, 130.9, 130.7, 129.3, 128.9, 120.8, 117.5, 115.6.
reactions involving moisture sensitive reactants were executed 2‐(3‐Bromophenyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
using oven dried glassware. All the imidazopyridines were
prepared by our reported method.6e
General Experimental Procedure for the Formylation of
Imidazo[1,2‐a]pyridines (1):
(
3f): White solid (53 mg, 88%), mp: 164‐166 °C; 1H NMR (CDCl3,
400 MHz): δ 10.04 (s, 1H), 9.63 (d, J = 6.8 Hz, 1H), 8.00‐7.99 (m,
1H), 7.79 (d, J = 9.2 Hz, 1H), 7.73‐7.71 (m, 1H), 7.64‐7.59 (m,
2H), 7.38 (t, J = 8.0 Hz, 1H), 7.15‐7.12 (m, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 179.2, 156.5, 147.7, 134.4, 132.9, 132.6,
130.7, 130.4, 128.9, 128.5, 123.1, 120.9, 117.6, 115.7; Anal.
Calcd for C14H9BrN2O: C, 55.84; H, 3.01; N, 9.30; Found: C,
55.64; H, 3.07; N, 9.41%.
Imidazo[1,2‐a]pyridine (1, 0.2 mmol), TMEDA (2, 0.4 mmol,
60 µL), KI (0.8 mmol, 132.8 mg) rose bengal (2.0 mol %, 4 mg),
and 1,4‐dioxane:H2O (5:1) (3 mL) were added to an oven‐dried
reaction vessel equipped with a magnetic stir bar, and the
reaction vessel was irradiated using a 20 W white LED bulb
(380‐750 nm) at room temperature under ambient air for 36 h.
The progress of the reaction was monitored by TLC. After
completion of the reaction, the reaction mixture was extracted
with ethyl acetate. The organic phase was dried over
anhydrous Na2SO4 and concentrated under reduced pressure
to get the crude residue which was purified by column
chromatography on silica gel (60−120 mesh) using petroleum
ether/ethyl acetate as an eluent to afford the pure formylated
products.
2‐(2‐Bromophenyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
3g): White solid (55 mg, 91%), mp: 136‐138 °C; 1H NMR
(CDCl3, 400 MHz): δ 9.74 (s, 1H), 9.59‐9.57 (m, 1H), 7.83‐7.80
(m, 1H), 7.74‐7.71 (m, 1H), 7.60‐7.54 (m, 2H), 7.46‐7.42 (m,
1H), 7.37‐7.33 (m, 1H), 7.17‐7.15 (m, 1H); 13C{1H} NMR (CDCl3,
100 MHz): δ 179.4, 157.0, 147.6, 133.5, 133.4, 132.6, 131.1,
130.3, 128.6, 127.5, 123.4, 121.1, 117.8, 115.7; Anal. Calcd for
C14H9BrN2O: C, 55.84; H, 3.01; N, 9.30; Found: C, 56.05; H,
3.06; N, 9.19%.
4‐(3‐Formylimidazo[1,2‐a]pyridin‐2‐yl)benzonitrile (3h): White
solid (40 mg, 82%), mp: 225‐227 °C; 1H NMR (CDCl3, 400 MHz):
δ 10.06 (s, 1H), 9.66‐9.64 (m, 1H), 7.96‐7.94 (m, 2H), 7.83‐7.81
(m, 3H), 7.65‐7.60 (m, 1H), 7.20‐7.16 (m, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 178.8, 155.7, 147.9, 136.9, 132.7, 131.0,
130.4, 128.9, 121.2, 118.4, 117.8, 116.0, 113.6; Anal. Calcd for
C15H9N3O: C, 72.87; H, 3.67; N, 16.99; Found: C, 72.68; H, 3.74;
N, 16.87.
2‐Phenylimidazo[1,2‐a]pyridine‐3‐carbaldehyde (
3a):8b White
solid (36 mg, 81%), mp: 126‐128 °C; 1H NMR (CDCl3, 400 MHz):
δ 10.06 (s, 1H), 9.65 (d, J = 6.8 Hz, 1H), 7.83‐7.79 (m, 3H), 7.59‐
7.50 (m, 4H), 7.13‐7.10 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz):
δ 179.7, 158.4, 147.8, 132.4, 130.5, 130.0, 129.9, 129.0, 128.9,
120.8, 117.5, 115.4.
2‐(p‐Tolyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde (3b): White
2‐(4‐(Trifluoromethyl)phenyl)imidazo[1,2‐a]pyridine‐3‐
carbaldehyde (3i): White solid (47 mg, 81%), mp: 116‐118 °C;
solid (40 mg, 85%), mp: 166‐168 °C; 1H NMR (CDCl3, 400 MHz):
δ 10.04 (s, 1H), 9.64‐9.62 (m, 1H), 7.79‐7.76 (m, 1H), 7.72‐7.70
(m, 2H), 7.57‐7.53 (m, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.11‐7.07
(m, 1H), 2.42 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 179.7,
158.5, 147.8, 140.1, 130.4, 129.8, 129.7, 129.5, 128.8, 120.7,
117.4, 115.2, 21.5; HRMS (ESI‐TOF) m/z: [M + H]+ Calcd for
C15H13N2O: 237.1022; Found: 237.1020.
1H NMR (CDCl3, 400 MHz): δ 10.06 (s, 1H), 9.67‐9.65 (m, 1H),
7.95 (d, J = 8.4 Hz, 2H), 7.84‐7.78 (m, 3H), 7.64‐7.59 (m, 1H),
7.18‐7.15 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 179.1,
156.5, 147.9, 136.0, 132.0, 130.8, 130.6, 129.6, (q, JC−F = 270
Hz), 125.9 (q, JC−F = 7 Hz), 122.7, 121.1, 117.7, 115.8; HRMS
(ESI‐TOF) m/z: [M + H]+ Calcd for C15H9F3N2O: 291.0745;
Found: 291.0743.
2‐(4‐Methoxyphenyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
3c): White solid (44 mg, 87%), mp: 146‐148 °C; 1H NMR (CDCl3,
2‐(2‐Hydroxyphenyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
400 MHz): δ 10.04 (s, 1H), 9.66‐9.64 (m, 1H), 7.79‐7.77 (m, 3H),
7.59‐7.54 (m, 1H), 7.12‐7.08 (m, 1H), 7.06‐7.04 (m, 2H), 3.88 (s,
3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 179.6, 161.2, 158.3,
147.9, 131.3, 130.5, 128.9, 124.9, 120.6, 117.3, 115.2, 114.5,
55.5; Anal. Calcd for C15H12N2O2: C, 71.42; H, 4.79; N, 11.10;
Found: C, 71.67, H, 4.86; N, 11.01%.
(
3j): White solid (40 mg, 85%), mp: 160‐162 °C; 1H NMR (CDCl3,
400 MHz): δ 11.70 (brs, 1H), 10.26 (s, 1H), 9.73 (d, J = 6.8 Hz,
1H), 7.74 (d, J = 8.4 Hz, 1H), 7.66‐7.59 (m, 2H), 7.40‐7.36 (m,
1H), 7.16 (t, J = 6.8 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.98 (t, J =
7.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 179.5, 158.2,
155.5, 146.0, 132.1, 131.2, 129.9, 129.1, 120.3, 119.8, 118.2,
116.6, 115.9, 115.5; HRMS (ESI‐TOF) m/z: [M + H]+ Calcd for
C14H11N2O2: 239.0821; Found: 239.0823.
2‐(4‐Fluorophenyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
3d): White solid (39 mg, 82%), mp: 143‐145 °C; 1H NMR
(CDCl3, 400 MHz): δ 10.02 (s, 1H), 9.64‐9.62 (m, 1H), 7.83‐7.77
2‐(4‐(Methylsulfonyl)phenyl)imidazo[1,2‐a]pyridine‐3‐
(m, 3H), 7.60‐7.56 (m, 1H), 7.24‐7.19 (m, 2H), 7.14‐7.10 (m,
carbaldehyde
(
3k): Light yellow solid (51mg, 86%), mp: 194‐
1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 179.3, 164.0 (d, JC−F
=
1
196 °C; H NMR (CDCl3, 400 MHz): δ 10.05 (s, 1H), 9.64‐9.62
(m, 1H), 8.09‐8.07 (m, 2H), 8.02‐8.00 (m, 2H), 7.80 (d, J = 9.2
Hz, 1H), 7.63‐7.59 (m, 1H), 7.18‐7.15 (m, 1H), 3.10 (s, 3H);
13C{1H} NMR (CDCl3, 100 MHz): δ 178.8, 155.5, 147.8, 141.5,
137.8, 131.0, 130.7, 128.9, 127.9, 121.2, 117.7, 116.0, 44.5;
248 Hz), 157.3, 147.8, 131.7 (d, JC−F = 8 Hz), 130.7, 128.9, 128.6
(d, JC−F = 3 Hz), 120.7, 117.5, 116.1 (d, JC−F = 21 Hz), 115.5; Anal.
Calcd for C14H10FN2O: C, 69.99; H, 3.78; N, 11.66; Found: C,
69.78; H, 3.83; N, 11.78%.
4 | J. Name., 2012, 00, 1‐3
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Anal. Calcd for C15H12N2O3S: C, 59.99; H, 4.03; N, 9.33; Found: 179.7, 158.0, 147.9, 132.6, 130.0, 129.7, 129.4, 128.9, 127.6,
C, 59.91; H, 4.09; N, 9.45%.
126.5, 121.2, 115.3, 17.1.
2‐(Naphthalen‐2‐yl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
7‐Methyl‐2‐phenylimidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
1
3l): White solid (49 mg, 89%), mp: 210‐212 °C; 1H NMR (CDCl3,
3s):8b,8g White solid (41 mg, 86%), mp: 156‐158 °C; H NMR
400 MHz): δ 10.17 (s, 1H), 9.69‐9.67 (m, 1H), 8.30 (s, 1H), 8.00 (CDCl3, 400 MHz): δ 9.97 (s, 1H), 9.46 (d, J = 6.8 Hz, 1H), 7.80‐
(d, J = 8.4 Hz, 1H), 7.97‐7.95 (m, 2H), 7.93‐7.90 (m, 1H), 7.85‐ 7.77 (m, 2H), 7.52‐7.47 (m, 4H), 6.92‐6.90 (m, 1H), 2.46 (s, 3H);
7.83 (m, 1H), 7.62‐7.59 (m, 1H), 7.58‐7.55 (m, 2H), 7.16‐7.12 13C{1H} NMR (CDCl3, 100 MHz): δ 179.2, 158.5, 148.2, 142.2,
(m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 179.8, 158.3, 147.9, 132.5, 129.8, 129.0, 128.8, 127.9, 120.6, 117.7, 116.1, 21.7.
133.9, 133.2, 130.6, 130.0, 129.8, 128.9, 128.8, 128.7, 127.9, 8‐Methyl‐2‐(p‐tolyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
127.3, 126.9, 126.8, 121.1, 117.5, 115.4; Anal. Calcd for
C18H12N2O: C, 79.39; H, 4.44; N, 10.29; Found: C, 79.54; H, 400 MHz): δ 10.00 (s, 1H), 9.48 (d, J = 6.8 Hz, 1H), 7.71 (d, J =
(
3t): White solid (45 mg, 90%), mp: 120‐122 °C; 1H NMR (CDCl3,
4.40; N, 10.21%.
8.4 Hz, 2H), 7.33‐7.30 (m, 3H), 6.98 (t, J = 7.2 Hz, 1H), 2.69 (s,
3H), 2.42 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 179.7,
2‐(Naphthalen‐1‐yl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
3m): Light yellow solid (48 mg, 88%), mp: 108‐110 °C; 1H NMR 158.1, 147.9, 139.8, 129.87, 129.80, 129.6, 129.3, 127.5, 126.5,
(CDCl3, 400 MHz): δ 9.75 (s, 1H), 9.68‐9.66 (m, 1H), 8.20‐8.18 121.1, 115.2, 21.4, 17.0; Anal. Calcd for C16H14N2O: C, 76.78; H,
(m, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.86 (d, 5.64; N, 11.19%; Found: C, 76.96; H, 5.69; N, 11.31%.
J = 8.8 Hz, 1H), 7.66 (d, J = 7.2 Hz, 1H), 7.62‐7.55 (m, 2H), 7.54‐ 3‐Formylindolizine‐1‐carbonitrile (5a): Light yellow solid (29
7.48 (m, 2H), 7.17‐7.13 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): mg, 86%), mp: 173‐175 °C; 1H NMR (CDCl3, 400 MHz): δ 9.77 (s,
δ 179.6, 158.0, 147.7, 133.8, 132.2, 130.4, 130.2, 129.9, 129.3, 1H), 9.73‐9.71 (m, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.73 (s, 1H),
128.6, 128.4, 127.1, 126.4, 125.8, 124.9, 122.3, 117.6, 115.4; 7.53‐7.49 (m, 1H), 7.16‐7.13 (m, 1H); 13C{1H} NMR (CDCl3, 100
Anal. Calcd for C18H12N2O: C, 79.39; H, 4.44; N, 10.29; Found: C, MHz): δ 178.3, 141.4, 129.8, 129.3, 128.7, 124.2, 117.7, 116.4,
79.16; H, 4.39; N, 10.38%.
114.9, 85.9; Anal. Calcd for C10H6N2O: C, 70.58; H, 3.55; N,
2‐(Thiophen‐2‐yl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
3n): 16.46; Found: C, 70.45; H, 3.51; N, 16.50%.
Light yellow solid (38 mg, 84%), mp: 121‐123 °C; 1H NMR Methyl 3‐formylindolizine‐1‐carboxylate
(5b): White solid (37
(CDCl3, 400 MHz): δ 10.29 (s, 1H), 9.62‐9.59 (m, 1H), 7.75 (d, J mg, 90%), mp: 126‐128 °C; 1H NMR (CDCl3, 400 MHz): δ 9.76 (s,
= 8.8 Hz, 1H), 7.62‐7.61 (m, 1H), 7.57‐7.53 (m, 2H), 7.19‐7.17 1H), 9.73‐9.71 (m, 1H), 8.36 (d, J = 8.8 Hz, 1H), 7.92 (s, 1H),
(m, 1H), 7.11‐7.07 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 7.49‐7.45 (m, 1H), 7.10‐7.06 (m, 1H), 3.92 (s, 3H); 13C{1H} NMR
178.6, 151.4, 147.9, 134.9, 130.8, 129.2, 128.98, 128.92, 128.3, (CDCl3, 100 MHz): δ 178.7, 164.3, 140.2, 129.5, 129.0, 128.5,
120.1, 117.3, 115.4; Anal. Calcd for C12H8N2OS: C, 63.14; H, 124.0, 119.7, 115.8, 107.2, 51.5; Anal. Calcd for C11H9NO3: C,
3.53; N, 12.27; Found: C, 63.35; H, 3.47; N, 12.15%.
65.02; H, 4.46; N, 6.89; Found: C, 65.18; H, 4.39; N, 6.81%.
2‐Isobutylimidazo[1,2‐a]pyridine‐3‐carbaldehyde
(
3o): Brown
1
gummy mass (38 mg, 95%); H NMR (CDCl3, 400 MHz): δ 9.96
(s, 1H), 9.52‐9.50 (m, 1H), 7.67‐7.65 (m, 1H), 7.51‐7.46 (m, 1H),
7.05‐7.01 (m, 1H), 2.86 (d, J = 7.2 Hz, 2H), 2.23‐2.16 (m, 1H),
0.98 (d, J = 6.8 Hz, 6H); 13C{1H} NMR (CDCl3, 100 MHz): δ 177.3,
160.6, 147.8, 130.1, 128.5, 121.7, 116.9, 114.9, 37.1, 29.6,
22.6; Anal. Calcd for C12H14N2O: C, 71.26; H, 6.98; N, 13.85;
Found: C, 71.07; H, 7.04; N, 13.92%.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
A.H. acknowledges the financial support from CSIR, (Grant
no.02(0307)/17/EMR-II).
2‐Cyclopropylimidazo[1,2‐a]pyridine‐3‐carbaldehyde
(3p):
Light yellow solid (35 mg, 93%), mp: 118‐120 °C; 1H NMR
(CDCl3, 400 MHz): δ 10.09 (s, 1H), 9.46 (d, J = 6.4 Hz, 1H), 7.56
(d, J = 9.2 Hz, 1H), 7.46‐7.42 (m, 1H), 7.00‐6.96 (m, 1H), 2.37‐
2.31 (m, 1H), 1.27‐1.23 (m, 2H), 1.15‐1.11 (m, 2H); 13C{1H}
NMR (CDCl3, 100 MHz): δ 176.7, 163.0, 148.1, 130.2, 128.5,
121.6, 116.5, 114.5, 10.3, 8.5; HRMS (ESI‐TOF) m/z: [M + H]+
Calcd for C11H11N2O: 187.0871; Found: 187.0871.
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6 | J. Name., 2012, 00, 1‐3
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DOI: 10.1039/C8OB00532J
Visible light induced tetramethylethylenediamine assisted formylation of
imidazopyridines
Golam Kibriya,a Avik K. Bagdi,b and Alakananda Hajra*a
aDepartment of Chemistry, Visva-Bharati (A Central University), Santiniketan 731235, India
bDepartment of Chemistry, TDB College, Raniganj, Paschim Bardhaman 713347, India.
A metal-free visible light induced C-3 formylation of imidazo[1,2-a]pyridine has been
developed using tetramethylethylenediamine (TMEDA) as one carbon source under ambient
air.