(Diacetoxy)iodobenzene-Mediated Oxidative C-H Amination of Imidazopyridines at Ambient Temperature

Article abstract of DOI:10.1021/acs.joc.7b00564

(Diacetoxy)iodobenzene (PIDA)-mediated direct oxidative C-H amination for the synthesis of 3-amino substituted imidazopyridines has been achieved under metal-free conditions at room temperature in short reaction times. This methodology is also applicable for the regioselective amination of indolizines. Experimental results suggest that the reaction likely proceeds through a radical pathway.

Full text of DOI:10.1021/acs.joc.7b00564

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Note
(Diacetoxy)iodobenzene-mediated Oxidative C-H
Amination of Imidazopyridines at Ambient Temperature
Susmita Mondal, Sadhanendu Samanta, Sourav Jana, and Alakananda Hajra
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00564 • Publication Date (Web): 06 Apr 2017
Downloaded from http://pubs.acs.org on April 6, 2017
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(
Diacetoxy)iodobenzene-mediated Oxidative C-H Amination of
Imidazopyridines at Ambient Temperature
Susmita Mondal, Sadhanendu Samanta, Sourav Jana, and Alakananda Hajra*
Department of Chemistry, VisvaꢀBharati (A Central University), Santiniketan 731235, India
Email: alakananda.hajra@visvaꢀbharati.ac.in
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Abstract:
(
Diacetoxy)iodobenzene (PIDA)ꢀmediated direct oxidative CꢀH amination for the synthesis of 3ꢀ
amino substituted imidazopyridines has been achieved under metalꢀfree conditions at room
temperature in short reaction times. This methodology is also applicable for the regioselective
amination of indolizines. Experimental results suggest that the reaction likely proceeds through a
radical pathway.
The development of efficient and sustainable methods for the construction of CꢀN bond
have a great importance in organic synthesis due to the wide occurrence of nitrogenꢀcontaining
molecules in natural products, synthetic intermediates, pharmaceutical agents, and biologically
1
2
active compounds. There are number of methodologies for the C(sp )−N bond formation
employing wellꢀknown strategies like Ullmann–Goldberg, Buchwald–Hartwig and Chan–Lam
2
aminations. However transitionꢀmetal catalysts and preꢀactivated substrates are the necessities
for these methodologies. As a consequence, recently much attention has been paid on the direct
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CꢀH amination of C(sp )−H bond due to its straightforwardness. In this context iodine(III)ꢀ
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mediated oxidative C(sp )−H amination has emerged as an important strategy. Intramolecular
oxidative amination of aromatic C−H bonds using hypervalent iodine have been found to
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construct various heterocyclic compounds, however the intermolecular amination of arenes and
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a
heteroarenes under metalꢀfree conditions have been less explored. Recently Chang et al.
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DeBoef et al. and Antonchick et al. have developed iodine(III) mediated intermolecular
oxidative amination of arenes.
7
Imidazo[1,2ꢀa]pyridine, an important class of biologically active nitrogen containing
fused heterocycles have a wide applications in pharmaceutical chemistry as well as in material
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sciences. There are several marketed drugs such as alpidem, zolpidem, necopidem, saripidem,
olprinone, zolimidine, etc., contain this scaffold. As a consequence this moiety has gained much
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interest of the synthetic chemists.
Among the various functionalized imidazopyridines, 3ꢀ
aminoimidazo[1,2ꢀa]pyridines are very important in medicinal chemistry. Very recently Charette
et al. reported a facile method for the synthesis of 3ꢀaminoimidazo[1,2ꢀa]pyridine from NꢀBocꢀ
1
1
protected 2ꢀaminopyridineꢀcontaining amides via cyclodehydration-aromatization. However, to
the best of our knowledge, there is no method for the direct intermolecular oxidative amination
of imidazo[1,2ꢀa]pyridines. Herein, we report a direct CꢀH amination of imidazopyridines using
PIDA as an oxidant at room temperature in short reaction time (Scheme 1).
Scheme 1. Direct Oxidative Amination of Imidazopyridines
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For the optimization of the reaction conditions, we started our study by taking 2ꢀ
phenylimidazo[1,2ꢀa]pyridine 1a and morpholine 2a as model substrates using PIDA in different
solvents (Table 1). Initially we carried out the reaction using 2 equiv of PIDA in THF at room
temperature (Table 1, entry 1). Gratifyingly, the coupling product 4ꢀ(2ꢀphenylimidazo[1,2ꢀ
a]pyridinꢀ3ꢀyl)morpholine (3aa) was obtained in 67% yield after 10 min. Inspired by this initial
result, we checked the effect of different solvents such as DCM, acetonitrile, toluene, 1,4ꢀ
dioxane, 1,2ꢀdichloroethane, ethanol, chlorobenzene and DMF (Table 1, entries 2ꢀ9). The best
result was obtained in 1,4ꢀdioxane affording 76% of the desired product (Table 1, entry 5). No
formation of the product was obtained in presence of bis(trifluoroacetoxy)iodobenzene (PIFA)
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(
Table 1, entry 10). Trace amount of product was obtained by using catalytic amount of PIDA
0.1 equiv) in presence of other oxidant such as K S O , TBHP (Table 1, entries 11 and 12). The
(
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yield was decreased with decreasing the amount of PIDA but remains same by using 3 equiv
PIDA (Table 1, entries 13 and 14). No significant increment of the yield was observed on
increasing the temperature even after 1 h (Table 1, entry 15). Thus the optimized reaction
conditions was obtained in presence of 2 equiv of PIDA in 1,4ꢀdioxane at room temperature for
10 min (Table 1, entry 5).
a
Table 1. Optimization of the Reaction Conditions
entry
oxidant
equiv)
solvent
yield (%)
(
1
2
PIDA (2)
PIDA (2)
THF
67
59
DCM
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PIDA (2)
PIDA (2)
PIDA (2)
PIDA (2)
PIDA (2)
PIDA (2)
PIDA (2)
PIFA (2)
K S O (2)
CH CN
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Toluene
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EtOH
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trace
nd
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1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
b
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trace
trace
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2
2
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b
TBHP (2)
PIDA (1)
PIDA (3)
PIDA (2)
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78
c
15
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a
Reaction conditions: 0.2 mmol of 1a and 0.4 mmol of 2a in presence of 2 equiv PIDA in 2 mL
,4ꢀdioxane. 0.1 equiv PIDA. Reaction temperature 60 °C for 1 h. nd = not detected.
b
c
1
With the optimized reaction conditions in hand, we checked the substrate scopes of this
protocol to show the generality of this methodology (Scheme 2). Imidazo[1,2ꢀa]pyridines
bearing methyl substituent on pyridine ring at different positions efficiently reacted with
morpholine to afford the desired coupling products with good yields (3ba and 3ca). Presence of
electronꢀdonating substituent like –Me, –OMe group at the phenyl ring of imidazo[1,2ꢀ
a]pyridines also worked well (3da – 3fa). Halogens (–Cl, –F) containing imidazopyridines
afforded the corresponding products with moderate to good yields (3ga and 3ha). A strong
electronꢀwithdrawing group such as –CF also produced the product (3ia) with 72% yield. It is
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also notable that the marketed drug zolimidine reacted well to give the desired product (3ja).
Naphthalene and thiophene substituted imidazo[1,2ꢀa]pyridines also produced the desired
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product in excellent yields under the optimized reaction conditions (3ka and 3la). Aliphatic
substituted (Cꢀ2) imidazo[1,2ꢀa]pyridines produced a nonꢀseparable mixtures with morpholine.
The single crystal Xꢀray analysis of 3aa was performed to confirm the structure of the 4ꢀ(2ꢀ
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phenylimidazo[1,2ꢀa]pyridinꢀ3ꢀyl)morpholine.
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a
Scheme 2. Substrate Scopes of the Present Method
a
Reaction conditions: 0.2 mmol of 1 and 0.4 mmol of 2a in the presence of 2 equiv PIDA in 2
mL 1,4ꢀdioxane at room temperature for 10 min.
To extend the scope of the present methodology, we investigated the other cyclic amines
like thiomorpholine and piperidine (Scheme 3). Both thiomorpholine and piperidine efficiently
reacted with imidazo[1,2ꢀa]pyridines to produce the desired coupling products. Imidazo[1,2ꢀ
a]pyridine containing both electronꢀdonating like ꢀOMe and electronꢀwithdrawing group such as
–
F, –Br and –CN on the phenyl ring of imidazo[1,2ꢀa]pyridine reacted with thiomorpholine to
afford the desired products with moderate to good yields (4fb, 4hb, 4mb and 4nb).
Thiomorpholine also reacted well with both naphthyl and heteroaryl substituted imidazo[1,2ꢀ
a]pyridine derivatives (4kb and 4ob). Imidazo[1,2ꢀa]pyridines bearing –Cl and ꢀMe substituent
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on the pyridine ring efficiently reacted with thiomorpholine to afford the desired products (4pb,
4bb and 4cb). Piperidine also reacted smoothly with different substituted imidazo[1,2ꢀ
a]pyridines (4ac, 4bc, 4fc and 4qc). Other cyclic and acyclic amines such as pyrrrolidine,
dibenzylamine, aniline, diisopropylamine were unable to produce the desired coupling products.
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Scheme 3. Substrate Scopes
N
H
N
R
Ar
N
PIDA (2 equiv)
N
R
Ar
N
1,4-dioxane
rt, 10 min
N
X
1
2
X
4
X = C, S
N
N
N
Br
OMe
F
N
N
N
N
N
N
N
N
N
S
S
S
S
4ab, 78%
4fb, 72%
4hb, 73%
4mb, 71%
N
N
N
N
O
CN
N
N
N
N
N
Cl
N
N
N
S
S
S
4
nb, 62%
4kb, 78%
S
4ob, 81%
4pb, 59%
Me
Me
Me
N
N
N
N
N
N
N
N
N
N
N
N
S
S
4bb, 86%
4ac, 62%b
4bc, 67%b
4cb, 76%
N
N
OMe
Cl
N
N
N
N
fc, 63%b
4qc, 65%b
4
a
Reaction conditions: 0.2 mmol of 1 and 0.4 mmol of 2 in the presence of 2 equiv PIDA in 2 mL
b
1,4ꢀdioxane at room temperature for 10 min. Reaction time 30 min.
This methodology is also applicable for the regioselective amination of indolizines
(Scheme 4). Morpholine, thiomorpholine and piperidine reacted smoothly with indolizines
affording moderate to good yields of the desired products (6aa, 6bb and 6cc).
a
Scheme 4. Subtrate Scopes of Indolizines
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a
Reaction conditions: 0.2 mmol of 5 and 0.4 mmol of 2 in the presence of 2 equiv PIDA in 2 mL
of 1,4ꢀdioxane at room temperature for 30 min.
Few controlled experiments were carried out to understand the mechanistic pathway of
the reaction (Scheme 5). The reaction did not proceed in presence of radical scavengers like 2,6ꢀ
diꢀtertꢀbutylꢀ4ꢀmethyl phenol (BHT), pꢀBenzoquinone (BQ), 2,3ꢀdichloroꢀ5,6ꢀdicyanoꢀ1,pꢀ
benzoquinone (DDQ) and 2,2,6,6ꢀtetramethylpiperidineꢀ1ꢀoxyl (TEMPO). However, 2,6ꢀdiꢀtertꢀ
butylꢀ4ꢀ(morpholinomethyl)phenol (7) was obtained under the optimized reaction conditions in
absence of 2ꢀphenylimidazo[1,2ꢀa]pyridine (1a) by the reaction of morpholine (2a) with BHT in
68% yield (Scheme 5, Eq. B). These results signify that the reaction proceeds through a radical
pathway.
Scheme 5. Controlled Experiments
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Based on the literature reports and our previous experiences on functionalization of
imidazo[1,2ꢀa]pyridines, here we proposed a radical mechanism for this coupling reaction
(Scheme 6). Initially Nꢀiodoamido species (A) is formed from the morpholine (2a) which
subsequently give morpholine radical (B). The resulting morpholine radical (B) reacts with
imidazo[1,2ꢀa]pyridine moiety (1a) to produce the radical intermediate (C) which consequently
affords the product (3aa) through the elimination of AcOH.
Scheme 6. Probable Mechanistic Pathway
Ph
PhI
I
AcO
OAc
OAc
Ph
O
NH
N
I
O
N
O
B
2
a
AcOH
A
AcO
N
Ph
N
N
N
1a
N
Ph
Ph
N
N
N
AcOH AcO
C
O
O
3
aa
In conclusion, we have developed a direct and straightforward method for the
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intermolecular oxidative amination of imidazopyridines through C(sp )−H functionalization
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employing PIDA as an oxidant. Mild and ambient reaction conditions, short reaction times,
broad substrate scopes are the notable advantages of this methodology. Experimental results
suggest that the reaction likely proceeds through a radical pathway. To the best of our knowledge
this is the first report for the direct intermolecular amination of imidazopyridines. The present
methodology is also applicable for the regioselective amination of indolizine derivatives. We
believe this metalꢀfree CꢀH amination strategy will gain much importance in organic synthesis,
medicinal chemistry as well as in material sciences.
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Experimental Section:
General Information: All reagents were purchased from commercial sources and used without
1
further purification. H NMR spectra were determined on 400 MHz spectrometer as solutions in
CDCl . Chemical shifts are expressed in parts per million (δ) and the signals were reported as s
3
(singlet), d (doublet), t (triplet), m (multiplet), and coupling constants (J) were given in Hz.
1
3
1
C{ H} NMR spectra were recorded at 100 MHz in CDCl solution. Chemical shifts as internal
3
1
13
1
standard are referenced to CDCl (δ = 7.26 for H and δ = 77.16 for C{ H} NMR) as internal
3
standard. TLC was done on silica gel coated glass slide. All solvents were dried and distilled
before use. Commercially available solvents were freshly distilled before the reaction. All
reactions involving moisture sensitive reactants were executed using oven dried glassware. Xꢀray
single crystal data were collected using MoKα (λ = 0.71073 Å) radiation with CCD area
1
0b
detector. All the imidazopyridines were prepared by our reported method.
Typical experimental procedure for the compound 3aa:
A mixture of 2ꢀphenylimidazo[1,2ꢀa]pyridine (1a) (0.2 mmol, 39 mg) and morpholine (2a) (0.4 mmol, 35
mg) were taken in a sealed tube. Then 1,4ꢀdioxane (2 mL) was added to it and stirred at room temperature
for few seconds. Then PIDA (2 equiv, 129 mg ) was added to it and stirred at room temperature for 10
min. After completion of the reaction (TLC), the reaction mixture was quenched with ethyl acetate (5 mL)
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and water (2 mL). Then the reaction mixture was extracted with ethyl acetate. The organic phase was
dried over anhydrous Na SO and concentrated under reduced pressure to get the crude residue which was
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purified by column chromatography on silica gel (60ꢀ120 mesh) using petroleum ether:ethyl acetate = 7:3
as an eluent to afford desired product (3aa) (42 mg, 76%) as a white solid.
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4-(2-Phenylimidazo[1,2-a]pyridin-3-yl)morpholine (3aa): White solid (76%, 42 mg); R = 0.45
f.
1
(
PE : EA = 70:30); M.p. 137ꢀ138 °C; H NMR (400 MHz, CDCl ): δ 8.11ꢀ8.09 (m, 1H), 7.86ꢀ
3
7
6
1
.84 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.47ꢀ7.43 (m, 2H), 7.37ꢀ7.33 (m, 1H), 7.18ꢀ7.14 (m, 1H),
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3
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.83ꢀ6.79 (m, 1H), 3.87 (t, J = 4.8 Hz, 4H), 3.16 (s, 4H); C{ H} NMR (100 MHz, CDCl ): δ
3
41.6, 137.8, 134.5, 128.8, 128.5, 128.3, 127.8, 124.3, 122.7, 117.9, 111.9, 67.9, 50.3; Anal.
Calcd for C H N O: C, 73.10; H, 6.13; N, 15.04%; Found: C, 73.25; H, 6.19; N, 15.13%.
1
7
17
3
4-(8-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)morpholine (3ba): White solid (84%, 49 mg);
1
R = 0.50 (PE : EA = 90:10); M.p. 147ꢀ148 °C; H NMR (400 MHz, CDCl ): δ 7.98 (d, J = 6.8
f.
3
Hz, 1H), 7.83ꢀ7.81 (m, 2H), 7.45 (t, J = 8.0 Hz, 2H), 7.37ꢀ7.35 (m, 1H), 6.98ꢀ6.96 (m, 1H), 6.74
13
1
(
t, J = 6.8 Hz, 1H), 3.86 (t, J = 4.4 Hz, 4H), 3.13 (s, 4H), 2.62 (s, 3H); C{ H} NMR (100 MHz,
CDCl ): δ 141.9, 137.4, 134.9, 129.1, 129.0, 128.3, 127.7, 123.1, 120.6, 111.9, 67.9, 50.5, 16.8;
3
Anal. Calcd for C H N O: C, 73.69; H, 6.53; N, 14.32%; Found: C, 73.85; H, 6.46; N, 14.24%.
1
8
19
3
4-(7-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)morpholine (3ca): White solid (73%, 43 mg);
1
R = 0.55 (PE : EA = 70:30); M.p. 148ꢀ149 °C; H NMR (400 MHz, CDCl ): δ 7.97 (d, J = 6.8
f.
3
Hz, 1H), 7.85ꢀ7.83 (m, 2H), 7.45ꢀ7.42 (m, 2H), 7.36ꢀ7.31 (m, 2H), 6.65ꢀ6.63 (m, 1H), 3.86 (t, J
13
1
=
4.8 Hz, 4H), 3.15 (s, 4H), 2.39 (s, 3H); C{ H} NMR (100 MHz, CDCl ): δ 142.1, 137.2,
3
135.3, 134.6, 128.7, 128.3, 128.1, 127.7, 122.1, 116.2, 114.6, 67.9, 50.3, 21.4; HRMS (ESIꢀ
+
+
+
TOF) m/z: [M+H] Calcd for C H N O [M + H] : 294.1606, found [M + H] : 294.1605.
1
8
19
3
4-(8-Methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)morpholine (3da): White solid (75%, 46 mg);
1
R = 0.50 (PE : EA = 75:25); M.p. 120ꢀ121 °C; H NMR (400 MHz, CDCl ): δ 7.97 (d, J = 6.8
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Hz, 1H), 7.72ꢀ7.70 (m, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.97ꢀ6.95 (m, 1H), 6.72 (t, J = 6.8 Hz, 1H),
13
1
3.85 (t, J = 4.4 Hz, 4H), 3.12 (s, 4H), 2.62 (s, 3H), 2.40 (s, 3H); C{ H} NMR (100 MHz,
CDCl ): δ 141.8, 137.5, 131.9, 129.09, 129.00, 128.7, 127.6, 125.9, 123.0, 120.5, 111.9, 67.9,
3
5
0.5, 21.4, 16.8; Anal. Calcd for C H N O: C, 74.24; H, 6.89; N, 13.67%; Found: C, 74.11; H,
19 21 3
10
11
12
13
14
15
16
17
18
19
20
21
22
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25
26
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39
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45
46
47
48
49
50
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6.93; N, 13.75%.
4-(2-(p-Tolyl)imidazo[1,2-a]pyridin-3-yl)morpholine (3ea): White solid (78%, 46 mg); R =
f.
1
0.60 (PE : EA = 70:30); M.p. 138ꢀ139 °C; H NMR (400 MHz, CDCl ): δ 8.11ꢀ8.09 (m, 1H),
3
7.74 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.26 (d, J = 7.6 Hz, 2H), 7.18ꢀ7.14 (m, 1H),
1
3
1
6.83ꢀ6.79 (m, 1H), 3.87 (t, J = 4.8 Hz, 4H), 3.16 (s, 4H), 2.40 (s, 3H); C{ H} NMR (100 MHz,
CDCl ): δ 141.6, 137.9, 137.6, 131.6, 129.1, 128.7, 128.3, 124.3, 122.7, 117.8, 111.9, 67.9, 50.3,
3
21.4; Anal. Calcd for C H N O: C, 73.69; H, 6.53; N, 14.32%; Found: C, 73.88; H, 6.58; N,
1
8
19
3
14.26%.
4-(2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl)morpholine (3fa): White solid (71%, 44
1
mg); R = 0.45 (PE : EA = 70:30); M.p. 165ꢀ166 °C; H NMR (400 MHz, CDCl ): δ 8.08 (d, J =
f.
3
6.8 Hz, 1H), 7.80ꢀ7.76 (m, 2H), 7.54 (d, J = 9.2 Hz, 1H), 7.16ꢀ7.12 (m, 1H),7.00ꢀ6.96 (m, 2H),
13
1
6.81ꢀ6.77 (m, 1H), 3.86 (t, J = 4.8 Hz, 4H), 3.85 (s, 3H), 3.15 (s, 4H); C{ H} NMR (100 MHz,
CDCl ): δ 159.4, 141.5, 137.6, 129.9, 127.9, 127.0, 124.2, 122.7, 117.7, 113.8, 111.8, 67.9, 55.3,
3
+
+
50.2; HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C H N O [M + H] : 310.1556, found [M +
18 19 3 2
+
H] : 310.1559.
4-(2-(4-Chlorophenyl)-8-methylimidazo[1,2-a]pyridin-3-yl)morpholine (3ga): White solid
1
(80%, 52 mg); R = 0.50 (PE : EA = 75:25); M.p. 160ꢀ161 °C; H NMR (400 MHz, CDCl ): δ
f.
3
7.97 (d, J = 6.8 Hz, 1H), 7.82ꢀ7.80 (m, 2H), 7.43ꢀ7.40 (m, 2H), 6.98ꢀ6.97 (m, 1H), 6.74 (t, J =
1
3
1
6.8 Hz, 1H), 3.86 (t, J = 4.4 Hz, 4H), 3.14 (s, 4H), 2.61 (s, 3H); C{ H} NMR (100 MHz,
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CDCl ): δ 142.1, 136.1, 133.6, 130.1, 129.0, 128.5, 127.8, 127.2, 123.3, 120.7, 112.1, 67.9, 50.3,
3
16.8; Anal. Calcd for C H ClN O: C, 65.95; H, 5.53; N, 12.82%; Found: C, 65.81; H, 5.48; N,
1
8
18
3
12.74%.
4-(2-(4-Fluorophenyl)imidazo[1,2-a]pyridin-3-yl)morpholine (3ha): White solid (74%, 44 mg);
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
R = 0.50 (PE : EA = 70:30); M.p. 158ꢀ159 °C; H NMR (400 MHz, CDCl ): δ 8.10 (d, J = 6.8
f.
3
Hz, 1H), 7.86ꢀ7.82 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.20ꢀ7.12 (m, 3H), 6.84ꢀ6.80 (m, 1H), 3.87
13
1
(
t, J = 4.8 Hz, 4H), 3.16 (s, 4H); C{ H} NMR (100 MHz, CDCl ): δ 162.6 (J = 245 Hz),
3 CꢀF
141.7, 136.8, 130.7 (JCꢀF = 4 Hz), 130.4 (JCꢀF = 9 Hz), 128.4, 124.5, 122.9, 117.9, 115.3 (JCꢀF
=
21 Hz), 112.0, 67.9, 50.3; Anal. Calcd for C H FN O: C, 68.67; H, 5.42; N, 14.13%; Found: C,
17 16 3
68.83; H, 5.37; N, 14.19%.
4-(2-(4-(Trifluoromethyl)phenyl)imidazo[1,2-a]pyridin-3-yl)morpholine (3ia): Yellow gummy
1
mass (72%, 50 mg); R = 0.60 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.14 (d, J =
f.
3
6.8 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 9.2 Hz, 1H), 7.24ꢀ
13
1
7.22 (m, 1H), 6.89ꢀ6.86 (m, 1H), 3.90 (t, J = 4.8 Hz, 4H), 3.20 (s, 4H); C{ H} NMR (100
MHz, CDCl ): δ 141.7, 136.6 (J = 185 Hz), 129.4 (JCꢀF = 74 Hz), 129.5, 128.6, 126.1 (JCꢀF = 9
3
CꢀF
Hz), 125.7, 125.5, 125.3 (JCꢀF = 8 Hz, 5 Hz), 123.0, 117.9, 112.4, 67.7, 50.0; Anal. Calcd for
C H F N O: C, 62.24; H, 4.64; N, 12.10%; Found: C, 62.40; H, 4.70; N, 12.01%.
18
16
3
3
4-(2-(4-(Methylsulfonyl)phenyl)imidazo[1,2-a]pyridin-3-yl)morpholine (3ja): Yellow gummy
1
mass (69%, 49 mg); R = 0.50 (PE : EA = 25:75); H NMR (400 MHz, CDCl ): δ 8.15 (t, J = 8.8
f.
3
Hz, 3H), 8.02 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.8 Hz, 1H), 7.24ꢀ7.22 (m, 1H), 6.89ꢀ6.86 (m,
13
1
1
H), 3.91 (t, J = 5.2 Hz, 4H), 3.22 (t, J = 4.4 Hz, 4H), 3.11 (s, 3H); C{ H} NMR (100 MHz,
CDCl ): δ 142.2, 140.0, 139.3, 129.1, 128.2, 127.8, 127.5, 125.3, 123.3, 118.3, 112.6, 67.8, 50.0,
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4.7; Anal. Calcd for C H N O S: C, 60.49; H, 5.36; N, 11.76%; Found: C, 60.30; H, 5.31; N,
18
19
3
3
11.84%.
4-(2-(Naphthalen-2-yl)imidazo[1,2-a]pyridin-3-yl)morpholine (3ka): Yellow gummy mass
1
(77%, 51 mg); R = 0.45 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.36 (s, 1H), 8.15ꢀ
f.
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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36
37
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49
50
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55
56
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59
60
8
.13 (m, 1H), 8.04ꢀ8.02 (m, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.88ꢀ7.86 (m, 1H), 7.64ꢀ7.61 (m, 1H),
.53ꢀ7.47 (m, 2H), 7.22ꢀ7.18 (m, 1H), 6.86ꢀ6.82 (m, 1H), 3.90 (t, J = 4.8 Hz, 4H), 3.23 (s, 4H);
7
13
1
C{ H} NMR (100 MHz, CDCl ): δ 141.8, 137.6, 133.4, 133.0, 131.8, 128.8, 128.5, 127.9,
3
127.8, 127.7, 126.7, 126.3, 126.2, 124.6, 122.9, 117.9, 112.1, 67.9, 50.3; Anal. Calcd for
C H N O: C, 76.57; H, 5.81; N, 12.76%; Found: C, 76.41; H, 5.88; N, 12.85%.
21
19
3
4-(2-(Thiophen-2-yl)imidazo[1,2-a]pyridin-3-yl)morpholine (3la): Yellow gummy mass (81%,
1
46 mg); R = 0.50 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.11ꢀ8.09 (m, 1H), 7.63ꢀ
f.
3
7.62 (m, 1H), 7.55ꢀ7.53 (m, 1H), 7.35ꢀ7.33 (m, 1H), 7.17ꢀ7.10 (m, 2H), 6.80ꢀ6.77 (m, 1H), 3.94
1
3
1
(t, J = 4.4 Hz, 4H), 3.28 (t, J = 4.8 Hz, 4H); C{ H} NMR (100 MHz, CDCl ): δ 142.0, 136.6,
3
133.6, 127.44, 127.41, 125.8, 125.6, 124.7, 123.3, 117.9, 112.1, 67.8, 49.5; HRMS (ESIꢀTOF)
+
+
+
m/z: [M+H] Calcd for C H N OS [M + H] : 286.1014, found [M + H] : 286.1021.
1
5
15
3
Typical experimental procedure for the compound 4ab:
A mixture of 2ꢀphenylimidazo[1,2ꢀa]pyridine (1a) (0.2 mmol, 39 mg) and thiomorpholine
(2b) (0.4 mmol, 41 mg) were taken in a sealed tube. Then 1,4ꢀdioxane (2 mL) was added to it
and stirred at room temperature for few seconds. Then PIDA (2 equiv, 129 mg ) was added to it
and stirred at room temperature for 10 min. After completion of the reaction (TLC), the reaction
mixture was quenched with ethyl acetate (5 mL) and water (2 mL). Then the reaction mixture
was extracted with ethyl acetate. The organic phase was dried over anhydrous Na SO and
2
4
concentrated under reduced pressure to get the crude residue which was purified by column
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chromatography on silica gel (60ꢀ120 mesh) using petroleum ether:ethyl acetate = 7:3 as an
eluent to afford desired product (4ab) (46 mg, 78%) as a yellow gummy mass.
4-(2-Phenylimidazo[1,2-a]pyridin-3-yl)thiomorpholine (4ab): Yellow gummy mass (78%, 46
1
mg); R = 0.50 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.07ꢀ8.05 (m, 1H), 7.88ꢀ7.85
f.
3
0
1
2
3
4
5
6
7
8
9
0
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1
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8
9
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0
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6
7
8
9
0
(m, 2H), 7.56 (d, J = 9.2 Hz, 1H), 7.48ꢀ7.44 (m, 2H), 7.38ꢀ7.34 (m, 1H), 7.19ꢀ7.15 (m, 1H),
13
1
6
.84ꢀ6.80 (m, 1H), 3.41 (t, J = 5.2 Hz, 4H), 2.81 (s, 4H); C{ H} NMR (100 MHz, CDCl ): δ
3
141.5, 137.4, 134.3, 129.9, 128.6, 128.4, 127.8, 124.5, 122.7, 117.9, 112.0, 52.7, 29.0; Anal.
Calcd for C H N S: C, 69.12; H, 5.80; N, 14.22%. Found: C, 68.93; H, 5.75; N, 14.14%.
1
7
17
3
4-(2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl)thiomorpholine (4fb): Colourless liquid
1
(
72%, 47 mg); R = 0.50 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.04 (d, J = 6.8 Hz,
f.
3
1H), 7.81ꢀ7.79 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.18ꢀ7.13 (m, 1H), 7.01ꢀ6.99 (m, 2H), 6.82ꢀ
13
1
6
.79 (m, 1H), 3.86 (s, 3H), 3.41ꢀ3.39 (m, 4H), 2.79 (s, 4H); C{ H} NMR (100 MHz, CDCl ): δ
3
159.4, 141.4, 137.3, 129.8, 129.2, 126.9, 124.2, 122.6, 117.7, 113.8, 111.8, 55.4, 52.6, 29.0;
Anal. Calcd for C H N OS: C, 66.43; H, 5.89; N, 12.91%; Found: C, 66.25; H, 5.94; N,
1
8
19
3
12.97%.
4-(2-(4-Fluorophenyl)imidazo[1,2-a]pyridin-3-yl)thiomorpholine (4hb): Yellow gummy mass
1
(73%, 46 mg); R = 0.60 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.06ꢀ8.04 (m, 1H),
f.
3
7.87ꢀ7.82 (m, 2H), 7.56ꢀ7.53 (m, 1H), 7.19ꢀ7.12 (m, 3H), 6.83ꢀ6.80 (m, 1H), 3.39 (t, J = 5.2 Hz,
1
3
1
4
H), 2.81 (s, 4H); C{ H} NMR (100 MHz, CDCl ): δ 162.6 (J = 246.0 Hz), 141.6, 136.5,
3 CꢀF
130.5 (JCꢀF = 3.0 Hz), 130.2 (JCꢀF = 8.0 Hz), 129.7, 124.5, 122.8, 117.9, 115.4 (JCꢀF = 22 Hz),
1
12.1, 52.7, 29.0; Anal. Calcd for C H FN S: C, 65.15; H, 5.15; N, 13.41%; Found: C, 65.31;
1
7
16
3
H, 5.21; N, 13.52%.
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-(2-(3-Bromophenyl)imidazo[1,2-a]pyridin-3-yl)thiomorpholine (4mb): Yellow gummy mass
1
(71%, 53 mg); R = 0.50 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.13 (s, 1H), 8.05
f.
3
(d, J = 6.8 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H),
7
.31 (t, J = 8.0 Hz, 1H), 7.20ꢀ7.15 (m, 1H), 6.82 (t, J = 6.8 Hz, 1H), 3.41 (t, J = 5.2 Hz, 4H),
10
11
12
13
14
15
16
17
18
19
20
21
22
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24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
3
1
2.83 (s, 4H); C{ H} NMR (100 MHz, CDCl ): δ 141.7, 136.4, 135.8, 131.3, 130.7, 130.1,
3
1
29.9, 126.8, 124.7, 123.0, 122.6, 118.1, 112.2, 52.5, 29.0; Anal. Calcd for C H BrN S: C,
17 16 3
5
4.55; H, 4.31; N, 11.23%; Found: C, 54.71; H, 4.24; N, 11.31%.
4-(3-Thiomorpholinoimidazo[1,2-a]pyridin-2-yl)benzonitrile (4nb): White solid (62%, 40 mg);
1
R = 0.50 (PE : EA = 70:30); M.p. 184ꢀ185 °C; H NMR (400 MHz, CDCl ): δ 8.09ꢀ8.05 (m,
f.
3
3
H), 7.75ꢀ7.72 (m, 2H), 7.57ꢀ7.55 (m, 1H), 7.23ꢀ7.19 (m, 1H), 6.87ꢀ6.83 (m, 1H), 3.44 (t, J = 5.2
13
1
Hz, 4H), 2.84 (s, 4H); C{ H} NMR (100 MHz, CDCl ): δ 142.0, 138.9, 135.2, 132.2, 130.8,
3
+
1
28.5, 125.1, 123.1, 119.0, 118.2, 112.5, 111.0, 52.3, 28.9; HRMS (ESIꢀTOF) m/z: [M+H]
+
+
Calcd for C H N S [M + H] : 321.1174, found [M + H] : 321.1193.
18 16
4
4-(2-(Naphthalen-2-yl)imidazo[1,2-a]pyridin-3-yl)thiomorpholine (4kb): Yellow gummy mass
1
(
78%, 54 mg); R = 0.45 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.37 (s, 1H), 8.11ꢀ
f.
3
8
.09 (m, 1H), 8.05ꢀ8.02 (m, 1H), 7.96ꢀ7.93 (m, 2H), 7.89ꢀ7.86 (m, 1H), 7.61 (d, J = 8.8 Hz, 1H),
1
3
1
7.52ꢀ7.49 (m, 2H), 7.22ꢀ7.18 (m, 1H), 6.86ꢀ6.82 (m, 1H), 3.47 (s, 4H), 2.84 (s, 4H); C{ H}
NMR (100 MHz, CDCl ): δ 141.7, 137.3, 133.4, 133.0, 131.6, 130.1, 128.5, 128.0, 127.8, 127.6,
3
1
26.5, 126.3, 126.2, 124.6, 122.8, 117.9, 112.1, 52.7, 29.0; Anal. Calcd for C H N S: C, 73.01;
21 19 3
H, 5.54; N, 12.16%; Found: C, 73.18; H, 5.60; N, 12.25%.
4
4
7
-(2-(Furan-2-yl)imidazo[1,2-a]pyridin-3-yl)thiomorpholine (4ob): Yellow gummy mass (81%,
1
6 mg); R = 0.50 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.11ꢀ8.09 (m, 1H), 7.58ꢀ
f.
3
.57 (m, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.17ꢀ7.13 (m, 1H), 6.90 (d, J = 3.6 Hz, 1H), 6.80ꢀ6.77 (m,
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H), 6.53ꢀ6.52 (m, 1H), 3.61 (s, 2H), 3.20 (s, 2H), 3.01 (s, 2H), 2.66 (s, 2H); C{ H} NMR (100
MHz, CDCl ): δ 149.2, 142.4, 141.5, 130.0, 129.5, 125.0, 122.5, 117.3, 112.0, 111.6, 108.1,
3
5
2.7, 29.3; Anal. Calcd for C H N OS: C, 63.13; H, 5.30; N, 14.73%; Found: C, 62.91; H,
15 15 3
5
.25; N, 14.64%.
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-(6-Chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)thiomorpholine (4pb): Light yellow gummy
1
mass (59%, 39 mg); R = 0.50 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.05 (d, J =
f.
3
2
.0 Hz, 1H), 7.83ꢀ7.81 (m, 2H), 7.52ꢀ7.45 (m, 3H), 7.37 (t, J = 7.2 Hz, 1H), 7.15ꢀ7.12 (m, 1H),
1
3
1
3.38 (s, 4H), 2.81 (s, 4H); C{ H} NMR (100 MHz, CDCl ): δ 139.8, 138.8, 134.0, 130.2,
3
1
28.6, 128.5, 128.1, 125.7, 120.54, 120.50, 118.4, 52.7, 29.0; Anal. Calcd for C H ClN S: C,
17 16 3
61.90; H, 4.89; N, 12.74%; Found: C, 61.72; H, 4.78; N, 12.63%.
4-(8-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)thiomorpholine (4bb): Yellow gummy mass
1
(
86%, 53 mg); R = 0.60 (PE : EA = 90:10); H NMR (400 MHz, CDCl ): δ 7.92 (d, J = 6.8 Hz,
f.
3
1
H), 7.85ꢀ7.82 (m, 2H), 7.47ꢀ7.43 (m, 2H), 7.36ꢀ7.32 (m, 1H), 6.96ꢀ6.94 (m, 1H), 6.72 (t, J = 6.8
1
3
1
Hz, 1H), 3.36 (t, J = 4.8 Hz, 4H), 2.84 (s, 4H), 2.61 (s, 3H); C{ H} NMR (100 MHz, CDCl ): δ
3
1
41.8, 137.0, 134.7, 130.2, 128.8, 128.4, 127.7, 127.6, 123.1, 120.5, 111.9, 52.8, 29.0, 16.7;
Anal. Calcd for C H N S: C, 69.87; H, 6.19; N, 13.58%; Found: C, 69.68; H, 6.14; N, 13.51%.
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8
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4-(7-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)thiomorpholine (4cb): Light yellow solid
1
(
76%, 47 mg); R = 0.50 (PE : EA = 70:30); M.p. 145ꢀ146 °C; H NMR (400 MHz, CDCl ): δ
f.
3
7
.93 (d, J = 7.2 Hz, 1H), 7.86ꢀ7.84 (m, 2H), 7.46ꢀ7.42 (m, 2H), 7.35ꢀ7.30 (m, 2H), 6.64ꢀ6.62 (m,
1
3
1
1H), 3.38 (d, J = 4.0 Hz, 4H), 2.81 (s, 4H), 2.39 (s, 3H); C{ H} NMR (100 MHz, CDCl ): δ
3
1
42.0, 136.9, 135.3, 134.5, 129.5, 128.5, 128.4, 127.6, 122.0, 116.2, 114.6, 52.7, 29.0, 21.4;
Anal. Calcd for C H N S: C, 69.87; H, 6.19; N, 13.58%; Found: C, 70.03; H, 6.13; N, 13.68%.
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-Phenyl-3-(piperidin-1-yl)imidazo[1,2-a]pyridine (4ac): Yellow liquid (62%, 34 mg); R =
f.
1
0.55 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.06ꢀ8.04 (m, 1H), 7.86ꢀ7.84 (m, 2H),
3
7.55 (d, J = 8.8 Hz, 1H), 7.44 (t, J = 8.0 Hz, 2H), 7.36ꢀ7.32 (m, 1H), 7.16ꢀ7.12 (m, 1H), 6.80ꢀ
1
3
1
6.77 (m, 1H), 3.09 (t, J = 5.2 Hz, 4H), 1.76ꢀ1.71 (m, 6H); C{ H} NMR (100 MHz, CDCl ): δ
3
10
11
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13
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141.5, 135.0, 131.0, 128.9, 128.8, 128.2, 127.5, 124.0, 123.1, 117.8, 111.6, 51.5, 27.1, 24.2;
Anal. Calcd for C H N : C, 77.95; H, 6.90; N, 15.15%; Found: C, 78.17; H, 6.80; N, 15.03%.
1
8
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8-Methyl-2-phenyl-3-(piperidin-1-yl)imidazo[1,2-a]pyridine (4bc): Yellow gummy mass (67%,
1
39 mg); R = 0.55 (PE : EA = 90:10); H NMR (400 MHz, CDCl ): δ 7.92 (d, J = 6.4 Hz, 1H),
f.
3
7.84ꢀ7.82 (m, 2H), 7.45ꢀ7.41 (m, 2H), 7.35ꢀ7.31 (m, 1H), 6.94ꢀ6.92 (m, 1H), 6.70 (t, J = 6.8 Hz,
1
3
1
1
H), 3.05 (t, J = 5.6 Hz, 4H), 2.62 (s, 3H), 1.83 (s, 1H), 1.74ꢀ1.68 (m, 5H); C{ H} NMR (100
MHz, CDCl ): δ 141.7, 136.6, 135.3, 130.7, 129.1, 128.2, 127.5, 127.4, 122.7, 120.9, 111.6,
3
+
+
5
1.7, 27.1, 24.2, 16.8; HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C H N [M + H] : 292.1814,
19 21 3
+
found [M + H] : 292.1831.
2-(4-Methoxyphenyl)-3-(piperidin-1-yl)imidazo[1,2-a]pyridine (4fc): Yellow gummy mass
1
(
63%, 39 mg); R = 0.50 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.03 (d, J = 6.8 Hz,
f.
3
1H), 7.80ꢀ7.78 (m, 2H), 7.53 (d, J = 9.2 Hz, 1H), 7.14ꢀ7.10 (m, 1H), 6.99ꢀ6.97 (m, 2H), 6.79ꢀ
1
3
1
6.75 (m, 1H), 3.86 (s, 3H), 3.08 (t, J = 5.6 Hz, 4H), 2.06 (s, 2H), 1.76ꢀ1.72 (m, 4H); C{ H}
NMR (100 MHz, CDCl ): δ 159.2, 141.4, 136.8, 130.0, 127.4, 123.9, 123.1, 117.5, 114.2, 113.7,
3
1
11.5, 55.4, 51.5, 27.1, 24.2; Anal. Calcd for C H N O: C, 74.24; H, 6.89; N, 13.67%; Found:
19 21 3
C, 74.41; H, 6.85; N, 13.68%.
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4
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-(4-Chlorophenyl)-3-(piperidin-1-yl)imidazo[1,2-a]pyridine (4qc): Yellow gummy mass (65%,
1
0 mg); R = 0.45 (PE : EA = 70:30); H NMR (400 MHz, CDCl ): δ 8.06ꢀ8.04 (m, 1H), 7.85ꢀ
f.
3
.81 (m, 2H), 7.55ꢀ7.53 (m, 1H), 7.43ꢀ7.39 (m, 2H), 7.17ꢀ7.13 (m, 1H), 6.81ꢀ6.77 (m, 1H), 3.09
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(
t, J = 5.6 Hz, 4H), 1.77ꢀ1.71 (m, 6H); C{ H} NMR (100 MHz, CDCl ): δ 134.0, 130.8, 129.9,
3
128.8, 128.6, 128.5, 125.5, 123.3, 117.3, 114.7, 112.6, 51.4, 26.9, 24.1; Anal. Calcd for
C H ClN : C, 69.34; H, 5.82; N, 13.48%; Found: C, 69.17; H, 5.90; N, 13.59%.
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Typical experimental procedure for the compound 6aa:
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A mixture of methyl indolizineꢀ1ꢀcarboxylate (5a) (0.2 mmol, 35 mg) and morpholine (2a) (0.4 mmol, 35
mg) were taken in a sealed tube. Then 1,4ꢀdioxane (2 mL) was added to it and stirred at room temperature
for few seconds. Then PIDA (2 equiv, 129 mg ) was added to it and stirred at room temperature for 30
min. After completion of the reaction (TLC), the reaction mixture was quenched with ethyl acetate (5 mL)
and water (2 mL). Then the reaction mixture was extracted with ethyl acetate. The organic phase was
dried over anhydrous Na SO and concentrated under reduced pressure to get the crude residue which was
2
4
purified by column chromatography on silica gel (60ꢀ120 mesh) using petroleum ether:ethyl acetate = 9:1
as an eluent to afford desired product (6aa) (38 mg, 73%) as a yellow gummy mass.
Methyl 3-morpholinoindolizine-1-carboxylate (6aa): Yellow gummy mass (73%, 38 mg); R =
f.
1
0
.55 (PE : EA = 90:10); H NMR (400 MHz, CDCl ): δ 8.14 (d, J = 8.8 Hz, 1H), 8.03 (d, J =
3
7
.2 Hz, 1H), 7.03ꢀ6.99 (m, 1H), 6.86 (s, 1H), 6.74ꢀ6.70 (m, 1H), 3.89ꢀ3.86 (m, 7H), 2.98 (t, J =
13
1
4
.8 Hz, 4H); C{ H} NMR (100 MHz, CDCl ): δ 165.5, 135.0, 132.6, 122.0, 121.9, 119.9,
3
1
12.1, 104.2, 101.3, 67.3, 52.3, 50.9; Anal. Calcd for C H N O : C, 64.60; H, 6.20; N, 10.76%;
1
4
16
2
3
Found: C, 64.77; H, 6.25; N, 10.66%.
3
0
7
-Thiomorpholinoindolizine-1-carbonitrile (6bb): Yellow gummy mass (71%, 34 mg); R =
f.
1
.50 (PE : EA = 85:15); H NMR (400 MHz, CDCl ): δ 7.99ꢀ7.97 (m, 1H), 7.60ꢀ7.57 (m, 1H),
3
.04ꢀ7.00 (m, 1H), 6.78ꢀ6.74 (m, 1H), 6.64 (s, 1H), 3.22 (t, J = 5.2 Hz, 4H), 2.83 (t, J = 4.4 Hz,
1
3
1
4H); C{ H} NMR (100 MHz, CDCl ): δ 135.7, 134.6, 131.8, 122.2, 121.9, 118.1, 117.3, 112.5,
3
1
05.7, 54.0, 28.3; Anal. Calcd for C H N S: C, 64.17; H, 5.39; N, 17.27%; Found: C, 64.01; H,
13 13 3
5
.47; N, 17.16%.
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-(Piperidin-1-yl)indolizine-1-carbonitrile (6cc): Yellow gummy mass (61%, 27 mg); R = 0.60
f.
1
(PE : EA = 90:10); H NMR (400 MHz, CDCl ): δ 7.98ꢀ7.96 (m, 1H), 7.58ꢀ7.56 (m, 1H), 7.00ꢀ
3
6.96 (m, 1H), 6.75ꢀ6.71 (m, 1H), 6.56 (s, 1H), 2.90 (t, J = 5.2 Hz, 4H), 1.77ꢀ1.72 (m, 4H), 1.65ꢀ
13
1
1
.60 (m, 2H); C{ H} NMR (100 MHz, CDCl ): δ 134.4, 130.9, 128.8, 122.5, 121.3, 117.8,
3
10
11
12
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117.6, 112.0, 104.0, 53.0, 26.1, 24.0; Anal. Calcd for C H N : C, 74.64; H, 6.71; N, 18.65%;
1
4
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3
Found: C, 74.80; H, 6.62; N, 18.58%.
3g
1
2
,6-di-tert-butyl-4-(morpholinomethyl)phenol (7) (68%, 42 mg): H NMR (400 MHz, CDCl ):
3
δ 7.09 (s, 2H), 5.13 (s, 1H), 3.71 (t, J = 4.8 Hz, 4H), 3.42 (s, 2H), 2.44 (t, J = 4.4 Hz, 4H), 1.44
1
3
1
(
s, 18H); C{ H} NMR (100 MHz, CDCl ): δ 152.9, 135.7, 128.1, 126.0, 67.2, 63.7, 53.6, 34.4,
3
30.5.
Acknowledgment: A.H. acknowledges the financial support from SERBꢀDST, (Grant no.
EMR/2016/001643). S.M. thanks CSIRꢀNew Delhi (CSIRꢀJRF) and S.S. thanks UGCꢀNew
Delhi (UGCꢀJRF) for their fellowships.
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13
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Supporting information: Scanned copies of H and C{ H} NMR spectra of the synthesized
compounds, CIF file for compound 3aa are available as supporting information. This material is
available free of charge via the Internet at http://pubs.acs.org.
References:
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0. (a) Bagdi, A. K.; Hajra, A. Chem. Rec. 2016, 16, 1868. (b) Bagdi, A. K.; Rahman, M.;
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12. (a) Cho, S. H.; Yoon, J.; Chang, S. J. Am. Chem. Soc. 2011, 133, 5996. (b) Boursalian, G.
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1
3. Further information can be found in the CIF file. This crystal was deposited in the
Cambridge Crystallographic Data Centre and assigned as CCDC 1535661
.
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4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
22
ACS Paragon Plus Environment