Copper-Catalyzed Tandem O-Arylation-Oxidative Cross Coupling: Synthesis of Chromone Fused Pyrazoles

Article abstract of DOI:10.1021/acs.joc.6b02890

Intermolecular tandem copper-catalyzed O-arylation-oxidative acylation (cross dehydrogenative coupling-CDC) has been developed under air as an oxidant. The reaction between 2,4-dihydro-3H-pyrazol-3-ones and ortho-halo aryl carboxaldehydes furnished the co

Full text of DOI:10.1021/acs.joc.6b02890

Subscriber access provided by University of Newcastle, Australia
Article
Copper [Cu]-Catalyzed Tandem O-Arylation–Oxidative
Cross Coupling: Synthesis of Chromone Fused Pyrazoles
Surisetti Suresh, Owk Obulesu, K. Harish Babu, and Jagadeesh Babu Nanubolu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02890 • Publication Date (Web): 22 Feb 2017
Downloaded from http://pubs.acs.org on February 23, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 31
The Journal of Organic Chemistry
1
2
3
4
5
Copper [Cu]-Catalyzed Tandem O-Arylation–Oxidative Cross
6
7
8
Coupling: Synthesis of Chromone Fused Pyrazoles
9
Owk Obulesu,†,‡ K. Harish Babu,† Jagadeesh Babu Nanubolu§ and Surisetti Suresh*,†,‡
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
†Organic and Biomolecular Chemistry Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT),
Hyderabad 500 007, India
‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology (CSIR-
IICT), Hyderabad 500 007, India
§Center for X-Ray Crystallography, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500
007, India
ABSTRACT: Intermolecular tandem copper catalyzed O-arylation–oxidative acylation (cross
dehydrogenative coupling-CDC) has been developed under air as an oxidant. The reaction
between 2,4-dihydro-3H-pyrazol-3-ones and ortho-halo aryl carboxaldehydes furnished the
corresponding chromone fused pyrazoles, in a straightforward manner. The synthetic utility of
the presented tandem catalysis has been demonstrated with the synthesis of an A2-subtype
selective adenosine receptor antagonist in only two steps.
---------------------------------------------------------------------------------------------------------------------
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 31
1
2
3
4
INTRODUCTION
5
6
7
8
9
Owing to its outstanding atom and step efficiencies, direct C-H bond functionalization has
emerged as a powerful tool in organic synthesis over the past decades. Transition metal catalyzed
C-H functionalization via C-H activation has received a great deal of attention from organic
chemists.1 In most of the cases, the success of these processes depends on the assistance from the
deliberate installation/design of the directing groups. Direct coupling between two C-H centers,
known as CDC or oxidative cross coupling (often via dual C-H activation), has proven to be one
of the most important methods for the construction of C-C bonds in the plethora of C-H
functionalization reactions.2 Intermolecular CDC between (aryl)aldehyde C-H bonds and olefin3
or arene4 C-H bonds, acylation of sp2 C-H bonds using aldehydes, has emerged as a method of
interest for the synthesis of aryl ketones (Figure 1, i). The intramolecular CDC processes provide
privileged bicyclic and tricyclic compounds with a ketone functionality.5 Xanthones,5c,d,f,h
thioxanthones,5h fluorenones,5d,g,h acridinones,5e,i isatins,5b pyrazole-chromone5j and indole-
indolone5k scaffolds etc. have been synthesized using this synthetic strategy (Figure 1, ii).
However, for such intramolecular transformations, the necessary precursor need to be pre-
synthesized. In most of these methods, the acylation of arenes with aldehydes rely on the use of
stoichiometric/excess amounts of expensive or unfriendly oxidizing agents.5 Although pure
molecular oxygen5b has been used as the oxidant of choice in the transition metal catalyzed CDC,
use of atmospheric air4a,6 would be more attractive. Development of methods to synthesize cyclic
ketones in an intermolecular fashion involving arylation-oxidative coupling (Figure 1, iii) using
air as an oxidant would be highly beneficial from the synthetic standpoint.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
ACS Paragon Plus Environment

Page 3 of 31
The Journal of Organic Chemistry
1
2
3
4
(i) Intermolecular acylation of sp2 C-H bond: Synthesis of acyclic ketones
5
6
7
8
O
DG
DG
O
O
O
H
H
R
(Het)Ar
(Het)Ar
R
H
R
H
R
9
R
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
R
DG = Directing Group
(ii) Intramolecular acylation of arene C-H bond: Synthesis of cyclic ketones
isatins
O
O
H
(thio)xanthones
acridinones
fluorenones
H
Z
(Het)Ar
Ar
Ar
(Het)Ar
Z
chromone fused pyrazoles
n
n
Z = O, S, NR; n = 0, 1
(iii) Intermolecular tandem arylation and acylation of arene C-H bond: Synthesis of
cyclic ketones chromone fused pyrazoles (This Work)
O
N
R2
O
X
R2
O
O
Tandem
Copper Catalysis
N
O
N
N
R1
+
Ar
Ar
N
N
R1
Air
O
NH2
3
2
1
A2-subtype selective adenosine
receptor antagonist
(iv) Recent multi-step approach for the synthesis of chromone fused pyrazoles
O
O
Li et al. (ref. 5j)
two steps
IL/TBHP
N
N
N
O
120 oC, 24 h
N
N
N
O
O
Ph
Ph
Ph
43.7% (in three steps - ref. 5j)
74% (one step-our work-3a)
Figure 1. Inter- and intramolecular CDC between sp2 C-H bonds of aldehydes and olefin/arene;
This Work.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 31
1
2
3
4
RESULTS AND DISCUSSION
5
6
7
8
We envisioned a synthetic strategy for the construction of cyclic ketones from intermolecular
reaction with the development of tandem arylation-oxidative coupling, obviating the synthesis of
specific intermediates. Continuing our interest in the development of tandem reactions triggered
by copper catalysis,7 we envisaged to develop tandem O-arylation-oxidative coupling process.
To test this hypothesis we have selected 2,4-dihydro-3H-pyrazol-3-ones 1 and 2-haloaryl
aldehydes 2 as coupling partners that would eventually lead to the synthesis of chromone fused
pyrazoles, chromeno[2,3-c]pyrazol-4(1H)-ones 3 (Figure 1, iii).8,9 Indeed, this kind of chromone
fused pyrazoles have shown important biological activities such as selective (A2A or A1)
adenosine receptor antagonist.8 It should be mentioned that the chromone fused pyrazoles have
been prepared using multi-step synthesis associated with harsh reaction conditions, use of excess
amounts of reagents/oxidants, prolonged reaction times and with the outcome of low overall
yields5j,8a-b,9 (for example, see Figure 1, iv).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
At the outset, we engaged in the development of tandem10 copper-catalyzed11 O-arylation12
followed by oxidative cyclization to synthesize 3―starting from 2,4-dihydro-3H-pyrazol-3-ones
1 and ortho-halo substituted aryl aldehydes 2 (Figure 1, iii). Initially, we chose 5-methyl-2-
phenyl-2,4-dihydro-3H-pyrazol-3-one 1a and 2-bromobenzaldehyde 2a as partners to test this
tandem reaction process.
We have preformed the reaction by using Cu(OAc)2 as a catalyst, 1,10-phenanthroline as a
ligand, and K2CO3 as a base in a vial, closed in the presence of air. Gratifyingly, this reaction
afforded the desired chromone fused pyrazole 3a in 54% yield (Table 1, entry 1). Encouraged by
this result, we have conducted an optimization study with respect to different transition metal
catalysts, ligands, and bases (Table 1; entries 1-12, for a detailed optimization study, see
ACS Paragon Plus Environment

Page 5 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
supporting information). As a result of this study, it turned out that the combination of CuI–1,10-
phenanthroline–K2CO3 proved to be the best among a set of conditions screened (Table 1, entry
4). Performing the reaction with optimized conditions (Table 1, entry 4) under inert atmosphere
of argon resulted in very low yield of the desired product which indicated that the reaction
requires air/oxygen (Table 1, entry 9). When the reaction was conducted under an oxygen
atmosphere, there was a decrease in the yield (Table 1, entry 10)―probably due to the oxidation
of the aldehyde under this condition. However, this tandem process was not successful with the
use of other transition metal compounds of Pd, Ru, Fe and In, under the reaction conditions (see
supporting information). It should be mentioned that in the absence of CuI/ligand the reaction
did not proceed (Table 1, entries 11 and 12). These experiments suggest that CuI is the choice of
the transition metal catalyst and air serves as the oxidant for such tandem catalysis.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
After having the set of optimized conditions, we focused our attention on extending the scope
of this process by using different 2,4-dihydro-3H-pyrazol-3-ones 1 and various ortho-halo
aromatic aldehydes 2 (Scheme 1). Primarily, we set on to evaluate the leaving halogen group in
this tandem process. It turned out that ortho-bromo substituted benzaldehyde gave better yields
of the desired product when compared to 2-chlorobenzaldehyde or 2-iodobenzaldehyde (see 3a,
Scheme 1 and supporting information for other leaving groups).
Later we studied the scope of this reaction using differently substituted ortho-
bromobenzaldehydes and 1a. Electron donating groups on ortho-bromobenzaldehydes 2d-2f
have tolerated well to give the corresponding chromone fused pyrazoles 3b-3d in good yields
(Scheme 1). The structure of the chromone fused pyrazole derivative 3d was also confirmed by
X-ray crystal structure analaysis (supporting information). Electron withdrawing group like
fluorine on ortho-bromobenzaldehyde gave the corresponding product 3e, albeit in moderate
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 31
1
2
3
4
5
6
7
8
9
yield (Scheme 1). The reaction of 1a and 2,5-dibromobenzaldehyde 2h gave the corresponding
bromo substituted chromone fused pyrazole 3f in 68% yield (Scheme 1).
Table 1. Optimization study.a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Entry
Metal Catalyst
Cu(OAc)2
Cu2O
CuBr
CuI
Ligand
1,10-phenanthroline
1,10-phenanthroline
1,10-phenanthroline
1,10-phenanthroline
DMEDA
Base
%yield of 3a
1
2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
K2CO3
K2CO3
K2CO3
K2CO3
54
32
3
58
4
74b
56
5
CuI
6
CuI
IMes
45
7
CuI
(L)-proline
64
8
CuI
1,10-phenanthroline
1,10-phenanthroline
1,10-phenanthroline
―
39
9
CuI
18c
16d
NR
NR
10
11
12
CuI
CuI
―
―
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), metal catalyst (0.05 mmol), ligand (0.1 mmol), base (1.65
mmol), DMSO (2 mL); [b] same result was obtained when the reaction was performed in a open vial; [c] Reaction
was performed under argon atmosphere in dry DMSO; [d] Reaction was performed under oxygen atmosphere in dry
ACS Paragon Plus Environment

Page 7 of 31
The Journal of Organic Chemistry
1
2
3
4
DMSO; DMEDA: N,N'-dimethylethylenediamine; IMes: 1,3-bis(2,4,6-trimethylphenyl)-imidazolium chloride; NR:
5
6
No Reaction.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
It is also interesting to note that chlorine also served as a good leaving group as 2,3-
dichlorobenzaldehyde 2i and 2,6-dichlorobenzaldehyde 2j provided the corresponding chromone
fused pyrazoles bearing chlorine substituents (3g and 3h, Scheme 1). ortho-Bromobenzaldehyde
bearing both electron withdrawing and donating substituents 2k afforded the corresponding
product 3i in good yield (Scheme 1). Tetracyclic chromone fused pyrazole 3j was synthesized in
good yield using of 1-bromo-2-napththaldehyde 2l (Scheme 1). The tandem process was well
successful by using different electron withdrawing groups and donating groups on pyrazole
systems 1b-1f, furnishing the diversely substituted chromone fused pyrazole frameworks 3k-3y
in moderate to good yields (Scheme 1). However, the reaction of N-Boc pyrazolone and 2-
bromobenzaldehyde did not give the desired product. The starting materials have been recovered.
This transformation was also not successful with heteroaromatic aldehydes such as 2-
chloronicotinaldehyde and pyrazolone 1a.
Scheme 1. Reaction of pyrazolones 1 and ortho-halo aryl aldehydes 2.a
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 31
1
2
3
4
5
6
7
8
9
O
O
O
O
OMe
3a, 74%; with 2a
3a, 25%; with 2b
3a, 52%; with 2c
N
N
N
N
N
N
O
Me
O
O
Ph
Ph
Ph
3b, 62%
3c, 65%
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
O
O
O
O
O
F
Br
O
O
N
N
Ph
N
N
N
N
N
N
Ph
O
O
Ph
Cl
Ph
3e, 45%
3f, 68%
3g, 56%
3d, 51%
O
O
O
O
O
Cl
OMe
F
N
N
N
N
O
N
N
Ph
N
O
N
O
Ph
Ph
3k, 63%
NO2
3j, 66%
3i, 64%
3h, 54%
O
O
O
O
O
Ph
N
Ph
OMe
O
O
OMe
N
N
N
N
O
N
O
N
N
O
Ph
Ph
3l, 47%
3m, 52%
3n, 60%
3o, 49%
NO2
O
NO2
O
O
O
n-Pr
Ph
O
Ph
Ph
N
F
Br
O
O
N
N
N
N
Ph
N
O
N
O
N
O
Ph
3s, 68%
Ph
3r, 49%
3q, 43%
3p, 51%
O
O
O
n-Pr
O
O
n-Pr
n-Pr
Br
F
OMe
N
N
N
N
N
N
O
3u, 65%
3v, 55%
3t, 64%
O
O
O
O
F3C
N
N
N
N
N
O
N
O
Ph
3y, 52%
3x, 35%
3w, 42%
ACS Paragon Plus Environment

Page 9 of 31
The Journal of Organic Chemistry
1
2
3
4
[a] Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), CuI (0.05 mmol), 1,10-phen (0.1 mmol), K2CO3 (1.65 mmol),
5
6
DMSO (2 mL).
7
8
9
To understand the reaction mechanism, we conducted some control experiments. To know
whether the reaction goes through a radical intermediate, we have added TEMPO (1 equiv) to the
reaction. In this case, the product 3a was formed in good yield which may indicate that no
radical intermediate is involved in this reaction pathway (see supporting information).
It was thought that the present tandem copper catalyzed O-arylation–oxidative acylation
would involve the intermediates 4 or 5 that could result from the sole O-arylation or sole
oxidative coupling, respectively (Scheme 2, top). We have monitored the reaction of 1a and 2a
by HRMS at different time intervals (after 1 h, 2 h, 4 h and 6 h) to find out whether the formation
of intermediates 4 or 5 occurs. From HRMS analysis, mass corresponding to the product 3a was
observed as a major peak while mass corresponding to the O-arylation intermediate 4 was also
observed as a minor peak. Our efforts to isolate this intermediate were not successful. No peak
corresponding to 5 was observed in HRMS. This suggests that the reaction might be going
through O-arylation followed by oxidative cross coupling via C-H activation. However, the
Friedel-Crafts type intermediate in the present tandem reaction may be ruled out due to the
reasons: (i) the reaction is conducted under basic medium, (ii) formation of condensation product
6 in the absence of the base (Scheme 2, bottom), probably via Friedel-Crafts type reaction,13 (iii)
significant drop in the yield of the product 3a with deuterated 1a-D (see, supporting
information). These experiments may suggest that C-H activation is the key step in the present
tandem process.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 31
1
2
3
4
5
6
Scheme 2. Control experiments.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Based on the literature report by Li and co-workers on a copper-catalyzed intramolecular C-
H oxidation/acylation5b and above control experiments, a plausible reaction mechanism may be
tentatively proposed for the present tandem catalysis (Scheme 3). Initially, intermediate I would
be formed by the oxidative addition of ortho-haloaryl aldehyde 2 with copper catalyst. In the
presence of base, pyrazole 1 would undergo complexation with intermediate I to give
intermediate II. Reductive elimination of II followed by complexation with the Cu(I) would lead
to the formation of intermediate III. The thus generated III would form an intermediate IV upon
oxidative insertion in the presence of oxygen. The intermediate IV would lead to the cyclized
ACS Paragon Plus Environment

Page 11 of 31
The Journal of Organic Chemistry
1
2
3
4
copper complex V that could finally undergo cyclization to give the product 3 upon reductive
5
6
elimination.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Scheme 3. Plausible Mechanism.
It is worth mentioning that the developed method has enabled to scale up the reaction to a
gram scale for the synthesis of 3a while maintaining high yield. Gram scale synthesis of
chromone fused pyrazole 3l and 3s was also performed (Scheme 4).
Scheme 4. Gram-scale syntheses of chromone fused pyrazoles 3a, 3l and 3s.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 31
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
We have subjected 3a to thionation using Lowesson's reagent to obtain the thione derivative
of the chromone fused pyrazole 7a in 93% yield.14 The thione analogs 7n and 7s were also
obtained in excellent yields (Scheme 5).
Scheme 5. Thionation of chromone fused pyrazole 3a, 3n and 3s.
ACS Paragon Plus Environment

Page 13 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
It is noteworthy that the potential of the present tandem method is demonstrated by the
synthesis of an A2-subtype selective adenosine receptor antagonist 8k. The method has also been
extended to the synthesis of interesting analogs 8l and 8m (Scheme 6). It is worth mentioning
that this synthesis has been accomplished in just couple of steps compared to the reported multi-
step synthesis for the same.8a,b
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Scheme 6. Synthesis of A2-subtype selective adenosine receptor antagonist 8a and
congeners 8l, 8m.
The benzyl group of N-benzyl substituted chromone fused pyrazole 3y was deprotected using
Pd/C catalyzed hydrogenolysis to obtain N-unsubstituted chromone fused pyrazole, 3-
methylchromeno[2,3-c]pyrazol-4(1H)-one 9 in excellent yield (Scheme 7).
Scheme 7. Deprotection of benzyl group of 3y.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 31
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
CONCLUSIONS
In conclusion, we have successfully developed copper catalyzed intermolecular tandem O-
arylation–oxidative cyclization using 2,4-dihydro-3H-pyrazol-3-ones and ortho-haloaryl
aldehydes under aerobic conditions. Notably, this method furnished the direct synthesis of
diversely substituted tricyclic and tetracyclic chromone fused pyrazoles in moderate to good
yields using commercially available starting materials. The synthetic utility of the chromone
fused pyrazoles has also been described for the synthesis of a representative A2-subtype selective
adenosine receptor antagonist in only two steps.
EXPERIMENTAL SECTION
General: All the reactions were carried out with an oven dried glassware or screw caped
vials. Reactions are magnetically stirred and monitored by analytical thin layer chromatography
(TLC). TLC was performed on silica gel 60 F254, UV lamp was used as visualizing agent. Iodine,
5% aqueous potassium permanganate solution were used as a developing agents followed by
heating. Purification of products was carried out by column chromatography by using 60-120
mesh silica and hexane, ethyl acetate were used as eluents, concentration under reduced pressure
o
was performed by rotary evaporator at 40-45 C. All the reagents and solvents are purchased
from commercial suppliers. Anhydrous/LR DMSO, catalysts, ligands, bases, and deuterated
solvents were used without further purification. 1H-NMR spectra were recorded on 300, 400 and
ACS Paragon Plus Environment

Page 15 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
500 MHz instruments. Chemical shifts (δ) are reported in ppm with the reference solvent and the
internal standards (TMS = 0; CDCl3 = 7.26). The following abbreviations were used to explain
the multiplicity of the spectra (s = singlet, d = doublet, dd = doublet of doublet, t = triplet, m =
multiplet). 13C-NMR spectra were recorded on 75, 100, and 125 MHz spectrometers. Mass
spectra was analysed by Electrospray Ionization (ESI) method on a LCMS mass spectrometer.
High resolution mass spectra were recorded on a quadrupole mass spectrometer. Melting points
(MP) were determined using a capillary point apparatus. MPs are uncorrected. Infrared
spectroscopy was performed as a neat sample or as a KBr sample on a FT-IR instrument.
General procedure for the synthesis of chromone fused pyrazoles 3a-y:- In a 10 mL
screw caped vial 2,4-dihydro-3H-pyrazol-3-one 1 (0.5 mmol), ortho-halo aryl aldehyde 2 (0.6
mmol), CuI (0.05 mmol, 9.5 mg), K2CO3 (1.65 mmol, 228 mg), 1,10-phenanthroline (0.1 mmol,
18 mg), and dimethyl sulfoxide (2 mL) were taken. Then the reaction vial was closed in the
presence of air. Then the reaction mixture was stirred at 120 oC for 6 h. The reaction mixture was
cooled to room temperature, diluted with water, extracted with ethyl acetate (2 x 20 mL), dried
over anhydrous Na2SO4 and filtered. The solvent was removed in vacuo to afford a crude
residue. The residue was purified by flash column chromatography (hexane/EtOAc, 95:5) on
silica gel to afford chromone fused pyrazole derivatives 3a-y.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
3-Methyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one5j 3a:- White solid, 102 mg (0.37
o
mmol), 74%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 169-171 C; IR (KBr) 1448, 1531, 1610,
1
1660, 2925, 3050 cm-1; H-NMR (300 MHz, CDCl3) δ = 2.72 (s, 3H), 7.38-7.44 (m, 1H), 7.47-
7.49 (m, 1H), 7.53-7.58 (m, 3H), 7.69-7.74 (m, 1H), 7.89-7.90 (m, 2H), 8.37 (dd, J1 = 7.9 Hz, J2
13
= 1.5 Hz, 1H); C{1H}NMR (125 MHz, CDCl3) δ = 14.1, 105.0, 117.6, 121.2, 123.4, 125.2,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 31
1
2
126.8, 127.3, 129.4, 133.7, 137.0, 148.1, 153.0, 154.5, 173.5; MS (ESI) m/z 277 [M+H]+;
HRMS (ESI, m/z): calcd for C17H13N2O2 [M+H]+ 277.0971, found 277.0974.
3
4
5
6
7
8
9
3,7-Dimethyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one 3b:- Light green solid, 90 mg
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
o
(0.31 mmol), 62%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 159-160 C; IR (KBr) 1139, 1438,
1534, 1621, 1658, 2923, 3060 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.51 (s, 3H), 2.71 (s, 3H),
7.28 (s, 1H), 7.35 (s, 1H), 7.38-7.41 (m, 1H), 7.52-7.57 (m, 2H), 7.88-7.90 (m, 2H), 8.24 (d, J =
8.0 Hz, 1H); 13C{1H}NMR (125 MHz, CDCl3) δ = 14.1, 21.7, 117.6, 121.2, 121.3, 126.6, 126.7,
127.3, 129.4, 137.3, 145.2, 148.2, 154.8, 173.6; MS (ESI) m/z 291 [M+H]+; HRMS (ESI, m/z):
calcd for C18H15N2O2 [M+H]+ 291.1128, found 291.1124.
6-Methoxy-3-methyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one5j 3c:- Yellow solid, 100
o
mg (0.32 mmol), 65%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 158-160 C; IR (KBr) 1281, 1469,
1536, 1617, 1660, 2926, 3070 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.72 (s, 3H), 3.93 (s, 3H),
7.26-7.28 (m, 1H), 7.38-7.41 (m, 1H), 7.46 (d, J = 9.0 Hz, 1H), 7.53-7.56 (m, 2H), 7.76 (d, J =
13
3.5 Hz, 1H), 7.88-7.90 (m, 2H); C{1H}NMR (125 MHz, CDCl3) δ = 14.2, 56.0, 104.7, 107.0,
118.8, 121.2, 122.8, 124.0, 127.3, 129.5, 137.2, 148.1, 149.1, 153.2, 160.0, 173.5; MS (ESI) m/z
307 [M+H]+; HRMS (ESI, m/z): calcd for C18H15N2O3 [M+H]+ 307.1077, found 307.1069.
3-Methyl-1-phenyl-[1,3]dioxolo[4',5':6,7]chromeno[2,3-c]pyrazol-4(1H)-one 3d:- Yellow
o
solid, 82 mg (0.25 mmol), 51%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 168-170 C; IR (KBr)
1257, 1482, 1533, 1629, 1652, 2911, 3065 cm-1; H-NMR (500 MHz, CDCl3) δ = 2.70 (s, 3H),
1
6.13 (s, 2H), 6.95 (s, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.53 (t, J = 8.5 Hz, 2H), 7.67 (s, 1H), 7.85-
7.87 (m, 2H); 13C{1H}NMR (125 MHz, CDCl3) δ = 14.1, 98.1, 102.8, 103.6, 104.6, 117.9,
121.1, 121.9, 126.5, 127.3, 129.0, 129.4, 137.1, 146.0, 147.8, 151.4, 152.6, 153.0, 172.8; MS
ACS Paragon Plus Environment

Page 17 of 31
The Journal of Organic Chemistry
1
2
(ESI) m/z 321 [M+H]+; HRMS (ESI, m/z): calcd for C18H13N2O4 [M+H]+ 321.0870, found
321.0877.
3
4
5
6
7
8
9
6-Fluoro-3-methyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one5j,9c 3e:- White solid, 66
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
o
mg (0.22 mmol), 45%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 168-170 C; IR (KBr) 1125, 1186,
1257, 1534, 1619, 1662, 2925, 3056 cm-1; H-NMR (500 MHz, CDCl3) δ = 2.69 (s, 3H), 7.39-
1
7.43 (m, 2H), 7.51-7.56 (m, 3H), 7.85-7.89 (m, 2H), 7.99 (dd, J1 = 8.2 Hz, J2 = 3.1 Hz, 1H);
13C{1H}NMR (100 MHz, CDCl3) δ = 13.9, 104.4, 111.8-112.0 (d, JC-F = 24.2 Hz), 119.3-119.4,
(d, JC-F = 8.1 Hz), 120.9, 121.2, 124.4-124.5 (d, JC-F = 7.3 Hz), 127.4, 129.4, 136.8, 147.8, 150.3,
152.8, 158.3, 160.7, 172.1; MS (ESI) m/z 295 [M+H]+; HRMS (ESI, m/z): calcd for
C17H12FN2O2 [M+H]+ 295.0877, found 295.0883.
6-Bromo-3-methyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one5j 3f:- White solid, 121 mg
o
(0.34 mmol), 68%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 156-158 C; IR (KBr) 1447, 1531,
1597, 1662, 2920, 3077 cm-1; 1H-NMR (400 MHz, CDCl3) δ = 2.68 (s, 3H), 7.38-7.44 (m, 2H),
7.52-7.56 (m, 2H), 7.76-7.78 (m, 1H), 7.85 (d, J = 8.0 Hz, 2H), 8.44 (s, 1H); 13C{1H}NMR (100
MHz, CDCl3) δ = 14.1, 104.9, 118.7, 119.5, 121.4, 124.9, 127.6, 129.5, 129.6, 136.6, 136.9,
148.3, 152.8, 153.3, 172.1; MS (ESI) m/z 355 [M+H]+; HRMS (ESI, m/z): calcd for
C17H12BrN2O2 [M+H]+ 355.0077, found 355.0090.
8-Chloro-3-methyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one 3g:- White solid, 87 mg
o
(0.28 mmol), 56%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 157-159 C; IR (KBr) 1461, 1504,
1600, 1671, 2926, 3075 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.72 (s, 3H), 7.38-7.42 (m, 2H),
7.55-7.58 (m, 2H), 7.78 (dd, J1 = 1.7 Hz, J2 = 7.8 Hz, 1H), 8.02-8.04 (m, 2H), 8.28 (dd, J1 = 1.7
13
Hz, J2 = 7.9 Hz, 1H); C{1H}NMR (125 MHz, CDCl3) δ = 14.2, 104.8, 120.5, 122.8, 125.1,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 31
1
2
125.4, 125.5, 127.3, 129.5, 134.2, 137.1, 148.3, 150.4, 152.5, 172.7; MS (ESI) m/z 311 [M+H]+;
HRMS (ESI, m/z): calcd for C17H12ClN2O2 [M+H]+ 311.0587, found 311.0589.
3
4
5
6
7
8
9
5-Chloro-3-methyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one 3h:- White solid, 84 mg
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
o
(0.27 mmol), 54%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 158-160 C; IR (KBr) 1450, 1532,
1604, 1662, 2926, 3058 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.72 (s, 3H), 7.39-7.44 (m, 2H),
7.53-7.58 (m, 3H), 7.84-7.86 (m, 2H), 8.30 (d, J = 8.5 Hz, 1H); 13C{1H}NMR (100 MHz,
CDCl3) δ = 14.2, 105.1, 117.9, 121.4, 122.1, 126.0, 127.7, 128.1, 129.5, 136.9, 139.7, 148.3,
152.8, 154.6, 172.7; MS (ESI) m/z 311 [M+H]+; HRMS (ESI, m/z): calcd for C17H12ClN2O2
[M+H]+ 311.0587, found 311.0589.
7-Fluoro-6-methoxy-3-methyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one 3i:- White
o
solid, 104 mg (0.32 mmol), 64%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 194-195 C; IR (KBr)
1457, 1504, 1618, 1663, 2964, 3058 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.70 (s, 3H), 4.00 (s,
3H), 7.29 (d, J = 10.5 Hz, 1H), 7.39-7.41 (m, 1H), 7.53-7.56 (m, 2H), 7.83-7.86 (m, 3H);
13C{1H}NMR (100 MHz, CDCl3) δ = 14.1, 56.6, 104.6, 105.7-105.9 (d, JC-F = 23.5 Hz), 108.5-
108.6 (d, JC-F = 2.9 Hz), 119.7, 121.3, 127.5, 129.5, 136.9, 146.1, 146.2, 148.5-148.6 (d, JC-F
=
11.7 Hz), 153.1, 154.1, 156.7, 172.6; MS (ESI) m/z 325 [M+H]+; HRMS (ESI, m/z): calcd for
C18H14FN2O3 [M+H]+ 325.0983, found 325.0989.
8-Methyl-10-phenylbenzo[7,8]chromeno[2,3-c]pyrazol-7(10H)-one 3j:- Yellow solid, 108
mg (0.33 mmol), 66%, Rf = 0.25 (EtOAc/Hexane, 5:95); MP 196-197 oC; IR (KBr) 1458, 1504,
1595, 1656, 2923, 3056 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.76 (s, 3H), 7.45-7.48 (m, 1H),
7.62-7.66 (m, 2H), 7.69-7.74 (m, 2H), 7.84 (d, J = 8.5 Hz, 1H), 7.96-8.02 (m, 3H), 8.32 (d, J =
8.5 Hz, 1H), 8.43-8.47 (m, 1H); 13C{1H}NMR (125 MHz, CDCl3) δ = 14.2, 105.6, 119.3, 121.3,
121.6, 121.9, 123.6, 125.2, 127.4, 127.5, 128.2, 129.2, 129.7, 136.3, 137.2, 148.1, 151.6, 152.7,
ACS Paragon Plus Environment

Page 19 of 31
The Journal of Organic Chemistry
1
2
173.7; MS (ESI) m/z 327 [M+H]+; HRMS (ESI, m/z): calcd for C21H15N2O2 [M+H]+ 327.1128,
found 327.1128.
3
4
5
6
7
8
9
3-Methyl-1-(3-nitrophenyl)chromeno[2,3-c]pyrazol-4(1H)-one 3k:- White solid, 102 mg
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
o
(0.32 mmol), 63%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 210-211 C; IR (KBr) 1455, 1532,
1612, 1664, 2924, 3113 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.73 (s, 3H), 7.49-7.53 (m, 1H),
7.62 (d, J = 8.0 Hz, 1H), 7.73-7.79 (m, 2H), 8.23-8.25 (m, 1H), 8.33-8.36 (m, 1H), 8.38 (dd, J1 =
13
8.0 Hz, J2 = 1.5 Hz, 1H), 8.90 (t, J = 2.5 Hz, 1H); C{1H}NMR (75 MHz, CDCl3) δ = 14.2,
105.5, 115.5, 117.8, 121.5, 123.4, 125.8, 126.0, 127.0, 130.5, 134.2, 138.2, 148.9, 149.3, 153.5,
154.5, 173.4; MS (ESI) m/z 322 [M+H]+; HRMS (ESI, m/z): calcd for C17H12N3O4 [M+H]+
322.0822, found 322.0821.
6-Methoxy-3-methyl-1-(3-nitrophenyl)chromeno[2,3-c]pyrazol-4(1H)-one8b 3l:- White
o
solid, 83 mg (0.24 mmol), 47%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 205-206 C; IR (KBr)
1424, 1492, 1533, 1610, 1667, 2933, 3102 cm-1; H-NMR (400 MHz, CDCl3) δ = 2.72 (s, 3H),
1
3.94 (s, 3H), 7.32 (dd, J1 = 9.2 Hz, J2 = 3.2 Hz, 1H), 7.54 (d, J1 = 9.2 Hz, 1H), 7.71-7.76 (m,
13
2H), 8.21-8.24 (m, 1H), 8.32-8.35 (m, 1H), 8.89 (t, J = 7.9 Hz, 1H); C{1H}NMR (125 MHz,
CDCl3) δ = 14.2, 56.1, 105.2, 107.1, 115.4, 118.9, 121.4, 123.1, 124.0, 125.9, 130.5, 138.2,
148.9, 149.0, 149.2, 153.6, 157.3, 173.3; MS (ESI) m/z 352 [M+H]+; HRMS (ESI, m/z): calcd
for C18H14N3O5 [M+H]+ 352.0928, found 352.0929.
3-Methyl-1-(3-nitrophenyl)-[1,3]dioxolo[4',5':6,7]chromeno[2,3-c]pyrazol-4(1H)-one
3m:- Yellow solid, 96 mg (0.26 mmol), 52%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 206-208 oC;
IR (KBr) 1256, 1535, 1664, 2919, 3099 cm-1; H-NMR (500 MHz, CDCl3) δ = 2.70 (s, 3H),
1
6.16 (s, 2H), 7.02 (s, 1H), 7.68 (s, 1H), 7.73 (t, J = 8.2 Hz, 1H), 8.21-8.23 (m, 1H), 8.29-8.31 (m,
1H), 8.85 (t, J = 2.2 Hz, 1H); 13C{1H}NMR (100 MHz CDCl3) δ = 14.1, 98.2, 102.9, 103.7,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 31
1
2
3
4
5
6
7
8
9
105.2, 115.3, 118.0, 121.4, 125.9, 130.5, 138.2, 146.4, 148.8, 148.9, 151.4, 152.9, 153.5, 172.6;
MS (ESI) m/z 366 [M+H]+; HRMS (ESI, m/z):calcd for C18H12N2O6 [M+H]+ 366.0721, found
366.0741.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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-Diphenylchromeno[2,3-c]pyrazol-4(1H)-one9b 3n:-White solid, 101 mg (0.30 mmol),
o
60%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 174-176 C; IR (KBr) 1403, 1457, 1517, 1609, 1659
cm-1; 1H-NMR (400 MHz, CDCl3) δ = 7.43-7.47 (m, 2H), 7.49-7.54 (m, 3H), 7.55-7.62 (m, 3H),
7.71-7.75 (m, 1H), 7.98-8.01 (m, 2H), 8.42-8.44 (m, 1H), 8.46-8.48 (m, 2H); 13C{1H}NMR (100
MHz, CDCl3) δ = 104.0, 117.4, 121.9, 123.5, 125.4, 127.4, 127.8, 128.4, 128.7, 129.5, 131.5,
133.9, 137.1, 149.9, 153.7, 153.8, 172.8; MS (ESI) m/z 339 [M+H]+; HRMS (ESI, m/z): calcd
for C22H15N2O2 [M+H]+ 339.1128, found 339.1128.
6-Methoxy-1,3-diphenylchromeno[2,3-c]pyrazol-4(1H)-one 3o:- White solid, 90 mg (0.24
o
mmol), 49%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 198-199 C; IR (KBr) 1456, 1486, 1521,
1606, 1652, 2923 cm-1; 1H-NMR (400 MHz, CDCl3) δ = 3.93 (s, 3H), 7.30 (dd, J1 = 3.0 Hz, J2
= 9.0 Hz, 1H), 7.42-7.53 (m, 5H), 7.60 (t, J = 7.5 Hz, 2H), 7.83 (d, J = 3.2 Hz, 1H), 7.97-8.02
(m, 2H), 8.44-8.49 (m, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ = 56.0, 103.7, 107.3, 118.6,
121.8, 123.2, 124.0, 127.7, 128.3, 128.7, 129.5, 131.6, 137.2, 148.4, 149.7, 153.9, 157.1, 172.7;
MS (ESI) m/z 369 [M+H]+; HRMS (ESI, m/z): calcd for C23H17N2O3 [M+H]+ 369.1234, found
369.1237.
1,3-Diphenyl-[1,3]dioxolo[4',5':6,7]chromeno[2,3-c]pyrazol-4(1H)-one 3p:- White solid,
o
98 mg (0.26 mmol), 51%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 218-219 C; IR (KBr) 1457,
1
1533, 1597, 1650 cm-1; H-NMR (500 MHz, CDCl3) δ = 6.13 (s, 2H), 6.96 (s, 1H), 7.42-7.46
(m, 2H), 7.51 (t, J = 7.0 Hz, 2H), 7.58 (t, J = 7.5 Hz, 2H), 7.72 (s, 1H), 7.95-7.97 (m, 2H), 8.44-
8.46 (m, 2H); 13C{1H}NMR (125 MHz, CDCl3) δ = 97.8, 102.8, 103.6, 104.0, 117.9, 121.7,
ACS Paragon Plus Environment

Page 21 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
127.7, 128.3, 128.7, 129.4, 129.5, 131.6, 137.1, 146.2, 149.5, 150.7, 152.8, 153.7, 171.9; MS
(ESI) m/z 383 [M+H]+; HRMS (ESI, m/z): calcd for C23H15N2O4 [M+H]+ 383.1026, found
383.1032.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
6-Bromo-1,3-diphenylchromeno[2,3-c]pyrazol-4(1H)-one 3q:- White solid, 89 mg (0.21
o
mmol), 43%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 208-209 C; IR (KBr) 1248, 1454, 1517,
1597, 1665, 2922 cm-1; 1H-NMR (400 MHz, CDCl3) δ = 7.44-7.49 (m, 3H), 7.50-7.53 (m, 2H),
7.57-7.61 (m, 2H), 7.81 (dd, J1 = 2.8 Hz, J2 = 9.0 Hz, 1H), 7.95-7.97 (m, 2H), 8.42-8.45 (m, 2H),
8.53 (d, J = 2.8 Hz, 1H); 13C{1H}NMR (75 MHz, CDCl3) δ = 103.9, 118.7, 119.3, 121.9, 124.9,
128.0, 128.4, 128.6, 129.5, 129.6, 130.1, 131.2, 136.8, 136.9, 149.9, 152.6, 153.5, 171.3; MS
(ESI) m/z 417 [M+H]+; HRMS (ESI, m/z): calcd for C22H14BrN2O2 [M+H]+ 417.0233, found
417.0228.
6-Fluoro-1,3-diphenylchromeno[2,3-c]pyrazol-4(1H)-one 3r:- White solid, 88 mg (0.25
o
mmol), 49%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 197-198 C; IR (KBr) 1449, 1465, 1520,
1
1622, 1659 cm-1; H-NMR (500 MHz, CDCl3) δ = 7.42-7.48 (m, 3H), 7.50-7.53 (m, 2H), 7.55-
7.57 (m, 1H), 7.57-7.61 (m, 2H), 7.96-7.98 (m, 2H), 8.07 (dd, J1 = 3.0 Hz, J2 = 8.5 Hz, 1H),
7.43-7.45 (m, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ = 103.5, 112.5-112.7 (d, JC-F = 24.2 Hz),
119.2-119.3 (d, JC-F = 8.0 Hz), 121.8, 121.9, 127.9, 128.4, 128.6, 129.5, 129.6, 131.3, 136.9,
149.7-149.8 (d, JC-F = 5.1 Hz), 153.8, 158.5, 160.9, 171.7; MS (ESI) m/z 357 [M+H]+; HRMS
(ESI, m/z): calcd for C22H14N2O2F [M+H]+ 357.1034, found 357.1038.
1-Methyl-3-propylchromeno[2,3-c]pyrazol-4(1H)-one 3s:- Yellow solid, 82 mg (0.34
o
mmol), 68%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 85-87 C; IR (KBr) 1455, 1563, 1613, 1665,
1
1828, 1959, 2959, 3067 cm-1; H-NMR (500 MHz, CDCl3) δ = 1.01 (t, J = 7.5 Hz, 3H), 1.80-
1.88 (m, 2H), 2.94 (t, J = 7.7 Hz, 2H), 3.90 (s, 3H), 7.41-7.44 (m, 1H), 7.47-7.49 (m, 1H), 7.66-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 31
1
2
13
7.69 (m, 1H), 8.34 (dd, J1 = 1.6 Hz, J2 = 7.9 Hz, 1H); C{1H}NMR (100 MHz, CDCl3) δ =
3
4
5
6
7
8
13.9, 21.9, 30.6, 33.7, 103.0, 117.3, 123.2, 124.9, 126.9, 133.5, 151.2, 153.8, 154.3, 173.1; MS
(ESI) m/z 243 [M+H]+; HRMS (ESI, m/z): calcd for C14H15N2O2 [M+H]+ 243.1128, found
243.1128.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
6-Methoxy-1-methyl-3-propylchromeno[2,3-c]pyrazol-4(1H)-one 3t:- White solid, 88 mg
o
(0.32 mmol), 64%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 169-171 C; IR (KBr) 1428, 1565,
1
1612, 1658, 1903, 2956, 3072 cm-1; H-NMR (500 MHz, CDCl3) δ = 1.01 (t, J = 7.5 Hz, 3H),
1.80-1.88 (m, 2H), 2.94 (t, J = 7.5 Hz, 2H), 3.89 (s, 3H), 3.91 (s, 3H), 7.23-7.25 (m, 1H), 7.41 (d,
J = 9.5 Hz, 1H), 7.44 (d, J = 3.0 Hz, 1H); 13C{1H}NMR (100 MHz, CDCl3) δ = 13.9, 21.9, 30.6,
33.7, 55.9, 102.8, 107.2, 118.5, 122.5, 123.9, 148.9, 151.1, 154.1, 156.7, 173.1; MS (ESI) m/z
273 [M+H]+; HRMS (ESI, m/z): calcd for C15H17N2O3 [M+H]+ 273.1234, found 273.1233.
6-Bromo-1-methyl-3-propylchromeno[2,3-c]pyrazol-4(1H)-one 3u:- Yellow solid, 104
o
mg (0.32 mmol), 65%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 169-171 C; IR (KBr) 1448, 1535,
1
1599, 1660, 1921, 2954, 3069 cm-1; H-NMR (500 MHz, CDCl3) δ = 1.00 (t, J = 7.5 Hz, 3H),
1.80-1.86 (m, 2H), 2.93 (t, J = 7.5 Hz, 2H), 3.90 (s, 3H), 7.36-7.39 (m, 1H), 7.73-7.76 (m, 1H),
13
8.41-8.43 (m, 1H); C{1H}NMR (100 MHz, CDCl3) δ = 13.9, 21.8, 30.5, 33.8, 103.0, 118.3,
119.2, 124.9, 129.8, 136.3, 151.4, 153.2, 153.8, 171.7; MS (ESI) m/z 321 [M+H]+; HRMS (ESI,
m/z): calcd for C14H14N2O2Br [M+H]+ 321.0233, found 321.0233.
6-Fluoro-1-methyl-3-propylchromeno[2,3-c]pyrazol-4(1H)-one 3v:- White solid, 72 mg
o
(0.28 mmol), 55%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 188-189 C; IR (KBr) 1451, 1569,
1
1622, 1664, 1909, 2963, 3081 cm-1; H-NMR (500 MHz, CDCl3) δ = 1.02 (t, J = 7.0 Hz, 3H),
1.79-1.87 (m, 2H), 2.94 (t, J = 7.5 Hz, 2H), 3.90 (s, 3H), 7.37-7.41 (m, 1H), 7.48 (dd, J1 = 4.0
Hz, J2 = 9.0 Hz, 1H), 7.97 (dd, J1 = 3.5 Hz, J2 = 8.0 Hz, 1H); 13C{1H}NMR (125 MHz, CDCl3)
ACS Paragon Plus Environment

Page 23 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
δ = 13.9, 21.9, 30.6, 33.8. 102.7, 112.3-112.5 (d, JC-F = 24.5 Hz), 119.0-119.1 (d, JC-F = 8.2 Hz),
121.1-121.3 (d, JC-F = 25.4 Hz), 124.8-124.9 (d, JC-F = 7.3 Hz), 150.4, 151.2, 154.0, 158.5, 160.5,
172.1; MS (ESI) m/z 261 [M+H]+; HRMS (ESI, m/z): calcd for C14H14N2O2F [M+H]+
261.1033, found 261.1034.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
3-tert-Butyl-1-methylchromeno[2,3-c]pyrazol-4(1H)-one 3w:- White solid, 55 mg (0.21
o
mmol), 42%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 163-164 C; IR (KBr) 1171, 1261, 1366,
1
1466, 1505, 1601, 2854, 2925, 2962, 3010 cm-1; H-NMR (500 MHz, CDCl3) δ = 1.50 (s, 9H),
3.90 (s, 3H), 7.41-7.44 (m, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.65-7.69 (m, 1H), 8.36 (dd, J1 = 1.5
Hz, J2 = 8.0 Hz, 1H); 13C{1H}NMR (125 MHz, CDCl3) δ =28.3, 33.7, 33.8, 102.4, 117.0, 123.4,
124.9, 127.4, 133.4, 153.8, 154.6, 159.1, 172.3; MS (ESI) m/z 257 [M+H]+; HRMS (ESI, m/z):
calcd for C15H17N2O2 [M+H]+ 257.1281, found 257.1280.
1-Methyl-3-(trifluoromethyl)chromeno[2,3-c]pyrazol-4(1H)-one 3x:- White solid, 47 mg
o
(0.18 mmol), 35%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 183-185 C; IR (KBr) 1455, 1558,
1610, 1671, 2924, 3060 cm-1; 1H-NMR (400 MHz, CDCl3) δ = 4.04 (s, 3H), 7.46-7.50 (m, 1H),
13
7.52-7.54 (m, 1H), 7.72-7.77 (m, 1H), 8.37 (dd, J1 = 1.6 Hz, J2 = 8.0 Hz, 1H); C{1H}NMR
(100 MHz, CDCl3) δ = 34.8, 102.6, 117.5, 118.7, 121.4, 122.9, 125.7, 127.5, 131.0, 134.5, 154.0,
154.1, 170.8; MS (ESI) m/z 269 [M+H]+; HRMS (ESI, m/z): calcd for C12H8N2O2F3 [M+H]+
269.0532, found 269.0534.
1-Benzyl-3-methylchromeno[2,3-c]pyrazol-4(1H)-one 3y:- White solid, 75 mg (0.26
o
mmol), 52%, Rf = 0.5 (EtOAc/Hexane, 10:90); MP 148-151 C; IR (KBr) 1493, 1554, 1611,
1659, 2929 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.62 (s, 3H), 5.38 (s, 3H), 7.29-7.37 (m, 5H),
7.41 (t, J = 7.2. Hz, 1H), 7.45-7.47 (m, 1H), 7.64-7.68 (m, 1H), 7.73 (dd, J1 = 1.6. Hz, J2 = 7.9.
13
1H); C{1H}NMR (125 MHz, CDCl3) δ = 14.4, 50.9, 103.7, 117.4, 123.4, 124.9, 126.9, 127.6,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 31
1
2
128.2, 128.9, 133.5, 135.2, 147.3, 153.7, 154.5, 173.4; MS (ESI) m/z 291 [M+H]+; HRMS (ESI,
3
4
5
6
m/z):calcd for C18H15N2O2 [M+H]+; 291.1128, found 291.1144.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Experimental procedure for the synthesis of 6:- In a 10 mL screw caped vial 2,4-dihydro-
3H-pyrazol-3-one 1a (0.5 mmol 87 mg), 2-bromobenzaldehyde 2a (0.6 mmol, 0.07 mL), copper
catalyst CuI or Cu(OTf)2 (0.05 mmol) and 1,10-phenanthroline (0.1 mmol, 18 mg) were taken in
DMSO (2 mL). The reaction vial was closed in the presence of air and it was stirred at 120 oC for
6 h. The reaction mixture was cooled to room temperature, diluted with water, extracted with
ethyl acetate (2 x 20 mL), dried over anhydrous Na2SO4 and filtered. The solvent was removed
in vacuo to afford a crude residue. The residue was purified by flash column chromatography
(hexane/EtOAc) on silica gel to afford the condensation product 6. The geometry of this
compound was found to be (Z) by nOe (see supporting information).
(Z)-4-(2-Bromobenzylidene)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one 6:- Red
o
colour solid, 157 mg (0.46 mmol), 92%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 128-130 C; IR
(KBr) 1463, 1593, 1635, 1687, 2920, 3425 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.38 (s, 3H),
7.18 (t, J = 7.3 Hz, 1H), 7.33-7.45 (m, 4H), 7.68 (dd, J1 = 1.0 Hz, J2 = 1.0 Hz, 1H), 7.79 (s, 1H),
7.91 (d, J = 9.6 Hz, 2H), 8.78 (dd, J1 = 1.5 Hz, J2 = 7.7 Hz, 1H); 13C{1H}NMR (100 MHz,
CDCl3) δ =13.3, 118.9, 125.0, 126.8, 127.3, 128.7, 128.8, 131.7, 132.9, 133.3, 133.5, 138.2,
144.5, 150.8, 161.4; MS (ESI) m/z 341 [M+H]+; HRMS (ESI, m/z): calcd for C17H14N2OBr
[M+H]+ 341.0284, found 341.0294.
Gram scale synthesis of chromone fused pyrazoles 3a, 3l and 3s:- In a 100 mL two necked
round bottom flask pyrazolone 1a or 1b or 1d (10 mmol), ortho-bromobenzaldehyde 2a or 2e
(12 mmol), CuI (1 mmol, 190 mg), K2CO3 (33 mmol, 4.55 g), 1,10-phenanthroline (2 mmol, 360
ACS Paragon Plus Environment

Page 25 of 31
The Journal of Organic Chemistry
1
2
mg), and dimethyl sulfoxide (30 mL) were taken. Then the reaction mixture was stirred at 120 oC
for 6 h in the presence of air. The reaction mixture was cooled to room temperature, diluted with
water, extracted with ethyl acetate (2 x 200 mL), dried over anhydrous Na2SO4 and filtered. The
solvent was removed in vacuo to afford a crude residue. The residue was purified by flash
column chromatography (hexane/EtOAc) on silica gel to afford chromone fused pyrazole
derivative 3a or 3l or 3s.
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Experimental procedure for thionation of chromone fused pyrazoles 3a, 3n and 3s:-
Chromone fused pyrazole 3a or 3n or 3s (0.5 mmol) was dissolved in 15 mL toluene and then
added Lawesson's reagent (0.25 mmol, 101 mg). Then the reaction mixture was heated at 140 oC
for 14 h and cooled to room temperature. The reaction mixture was extracted with ethyl acetate
(2 x 20 mL), dried over anhydrous Na2SO4 and filtered. The solvent was removed in vacuo to
afford a crude residue. The residue was purified by flash column chromatography
(hexane/EtOAc, 90:10) on silica gel to afford thione analogs 7a or 7n or 7s.
3-Methyl-1-phenylchromeno[2,3-c]pyrazole-4(1H)-thione14 7a:- Red solid, 136 mg (0.46
mmol), 93%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 185-187 oC; IR (KBr) 1440, 1537, 1588, 2921
cm-1; 1H-NMR (400 MHz, CDCl3) δ = 2.84 (s, 3H), 7.39-7.48 (m, 2H), 7.51-7.59 (m, 3H), 7.70-
7.74 (m, 1H), 7.89-7.93 (m, 2H), 8.81 (dd, J1 = 8.2 Hz, J2 = 2.0 Hz, 1H); 13C{1H}NMR (75
MHz, CDCl3) δ = 16.0, 116.3, 117.8, 121.3, 125.8, 127.6, 128.0, 129.4, 129.5, 133.7, 136.8,
146.6, 149.8, 150.9, 198.1; MS (ESI) m/z 293 [M+H]+; HRMS (ESI, m/z): calcd for
C17H13N2OS [M+H]+ 293.0743, found 293.0744.
1,3-Diphenylchromeno[2,3-c]pyrazole-4(1H)-thione 7n:- Brown solid, 167 mg (0.47
o
mmol), 94%, Rf = 0.3 (EtOAc/Hexane, 10:90); MP 210-212 C; IR (KBr) 1454, 1507, 1583,
1
1661, 2925 cm-1; H-NMR (500 MHz, CDCl3) δ = 7.42-7.47 (m, 5H), 7.53-7.59 (m, 3H), 7.70-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 31
1
2
3
4
7.73 (m, 1H), 7.88-7.90 (m, 2H), 7.98 (d, J = 7.6 Hz, 2H), 8.97 (dd, J1 = 1.3 Hz, J2 = 8.0 Hz,
5
6
13
1H); C{1H}NMR (100 MHz, CDCl3) δ = 115.2, 117.6, 121.7, 125.8, 127.6, 127.8, 128.4,
7
8
9
129.2, 129.5, 129.7, 130.2, 131.8, 133.7, 136.8, 147.0, 149.2, 152.1, 197.5; MS (ESI) m/z 355
[M+H]+; HRMS (ESI, m/z):calcd for C22H15N2OS [M+H]+ 355.0900, found 355.0917.
1-Methyl-3-propylchromeno[2,3-c]pyrazole-4(1H)-thione 7s:- Brown solid, 124 mg (0.48
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
o
mmol), 96%, Rf = 0.3 (EtOAc/Hexane, 10:90); MP 120-122 C; IR (KBr) 1448, 1527, 1580,
1665, 2863, 2928 cm-1; 1H-NMR (300 MHz, CDCl3) δ = 1.04 (t, J = 7.5 Hz, 3H), 1.74-1.87 (m,
2H), 3.14 (t, J = 7.7 Hz, 2H), 3.91 (s, 3H), 7.40-7.48 (m, 2H), 7.64-7.72 (m, 1H), 8.80 (dd, J1 =
13
1.6 Hz, J2 = 8.2 Hz, 1H); C{1H}NMR (125 MHz, CDCl3) δ = 13.9, 21.5, 30.8, 33.6, 114.7,
117.4, 125.3, 127.6, 129.4, 133.3, 147.5, 149.5, 153.4, 197.3; MS (ESI) m/z 259 [M+H]+;
HRMS (ESI, m/z):calcd for C14H15N2OS [M+H]+ 259.0900, found 259.0911.
Experimental procedure for the reduction of nitro group of 1-(3-
nitrophenyl)chromeno[2,3-c]pyrazol-4(1H)-ones:- 1-(3-Nitrophenyl)chromeno[2,3-c]pyrazol-
4(1H)-ones 3k or 3l or 3m (0.5 mmol), was dissolved in methanol (5 mL) and added Pd/C (10
wt.%, 106 mg). The reaction mixture was stirred at room temperature under hydrogen
atmosphere (H2 balloon) for 16 h. The reaction mixture was filtered on celite® pad, washed with
chloroform (20 mL) and the filtrate was concentrated to obtain the products, 1-(3-aminophenyl)-
chromeno[2,3-c]pyrazol-4(1H)-ones 8k or 8l or 8m without further purification.
1-(3-Aminophenyl)-3-methylchromeno[2,3-c]pyrazol-4(1H)-one8b 8k:- White solid, 63
o
mg (0.22 mmol), 43%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 259-260 C; IR (KBr) 1494, 1534,
1611, 1658, 2922, 3420 cm-1; 1H-NMR (400 MHz, CDCl3) δ = 2.70 (s, 3H), 6.68-6 71 (m, 1H),
7.20 (d, J = 2.0 Hz, 1H), 7.28-7.33 (m, 2H), 7.47 (t, J = 7.6 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H),
7.68-7.72 (m, 1H), 8.37 (dd, J1 = 1.6 Hz, J2 = 7.6 Hz, 1H); 13C{1H}NMR (125 MHz, CDCl3) δ =
ACS Paragon Plus Environment

Page 27 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
14.2, 105.0, 107.9, 111.2, 114.1, 117.7, 123.5, 125.2, 126.9, 130.2, 133.8, 138.0, 147.6, 148.0,
153.1, 154.6, 173.7; MS (ESI) m/z 292 [M+H]+; HRMS (ESI, m/z): calcd for C17H14N3O2
[M+H]+ 292.1080, found 292.1082.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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-Aminophenyl)-6-methoxy-3-methylchromeno[2,3-c]pyrazol-4(1H)-one8b 8l:- White
o
solid, 58 mg (0.18 mmol), 36%, Rf = 0.3 (EtOAc/Hexane, 5:95); MP 189-191 C; IR (KBr)
1470, 1613, 1659, 2928, 3371 cm-1; 1H-NMR (500 MHz, CDCl3) δ = 2.69 (s, 3H), 3.90 (s, 3H),
6.68 (d, J1 = 7.5. Hz, 1H), 7.19 (s, 1H), 7.24-7.25 (m, 1H), 7.27-7.32 (m, 2H), 7.44 (d, J = 9.2.
Hz, 1H), 7.73 (d, J = 3.0. Hz, 1H); 13C{1H}NMR (125 MHz, CDCl3) δ = 14.1, 55.9, 104.6,
106.9, 107.7, 110.9, 113.9, 118.8, 122.7, 123.9, 130.1, 137.9, 147.5, 147.8, 149.1, 153.2, 156.9,
173.5; MS (ESI) m/z 322 [M+H]+; HRMS (ESI, m/z):calcd for C18H16N3O3 [M+H]+ 322.1186,
found 322.1204.
1-(3-Aminophenyl)-3-methyl-[1,3]dioxolo[4',5':6,7]chromeno[2,3-c]pyrazol-4(1H)-one
8m:- Yellow solid, 68 mg (0.20 mmol), 40%, Rf = 0.4 (EtOAc/Hexane, 5:95); MP 195-197 oC;
1
IR (KBr) 1254, 1538, 1651, 2917, 3352 cm-1; H-NMR (500 MHz, CDCl3) δ = 2.68 (s, 3H),
6.12 (s, 2H), 6.68 (s, 1H), 6.69 (s, 1H), 7.17 (s, 1H), 7.22-7.24 (m, 1H), 7.27-7.30 (m, 1H), 7.67
(s, 1H); 13C{1H}NMR (125 MHz, CDCl3) δ = 14.1, 98.1, 102.7, 103.7, 110.9, 113.5, 117.9,
130.1, 137.9, 145.9, 147.6, 151.4, 152.5, 153.0, 172.7; MS (ESI) m/z 336 [M+H]+; HRMS (ESI,
m/z):calcd for C18H14N3O4 [M+H]+ 336.0979, found 336.0994.
Experimental procedure for the synthesis of 3-Methylchromeno[2,3-c]pyrazol-4(1H)-
one15 9:- 1-Benzyl-3-methylchromeno[2,3-c]pyrazol-4(1H)-one (0.5 mmol, 145 mg), was
dissolved in methanol (5 mL) and added Pd/C (10 wt.%, 106 mg). The reaction mixture was
stirred at room temperature under hydrogen atmosphere (H2 balloon) for 16 h. The reaction
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 31
1
2
3
4
5
6
mixture was filtered on celite® pad, washed with chloroform (20 mL) and the filtrate was
concentrated to obtain the product 9 in 92% yield, without further purification.
7
8
9
3-Methylchromeno[2,3-c]pyrazol-4(1H)-one15 9:- White solid, 92 mg (0.46 mmol), 92%,
Rf = 0.5 (EtOAc/Hexane, 10:90); MP 299-301 oC; IR (KBr) 1450, 1519, 1595, 1641, 3200 cm-1;
1H-NMR (300 MHz, DMSO-d6) δ = 2.60 (s, 3H), 7.26 (t, J = 7.2. Hz, 1H), 7.35-7.38 (m, 1H),
7.54-7.60 (m, 1H), 8.13 (dd, J1 = 1.4 Hz, J2 = 7.7 1H), 12.96 (broad singlet NH, 1H);
13C{1H}NMR (75 MHz, DMSO-d6) δ = 11.0, 103.1, 117.3, 122.1, 122.9, 125.7, 133.3, 140.4,
155.3, 161.2, 175.1; MS (ESI) m/z 201 [M+H]+; HRMS (ESI, m/z):calcd for C11H9N2O2
[M+H]+ 201.0659, found 201.0671.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
AUTHOR INFORMATION
Corresponding Author
* E-Mail: surisetti@iict.res.in; suresh.surisetti@yahoo.in
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank Department of Science and Technology (DST), India for Fast track grant (SB/FT/CS-
055/2012) and CSIR, New Delhi for financial support as part of XII Five Year plan under title
ORIGIN (CSC-0108). OO thanks CSIR, KHB thanks DST for fellowship and project
assistantship, respectively. We also thank Dr. G. V. Karunakar, CSIR-IICT, Dr. J. Raju Reddy,
Osmania University and Dr. D. V. Ramana, Central University of Jammu for their support.
ACS Paragon Plus Environment

Page 29 of 31
The Journal of Organic Chemistry
1
2
3
4
ASSOCIATED CONTENT
5
6
Supporting Information
7
8
9
The Supporting Information is available free of charge on the ACS Publications website at DOI:
10.1021/acs.joc.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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
Optimization data, control experiments, and spectra (PDF)
REFERENCES
(1) For selected recent reviews on C-H functionalization, see: (a) Ackermann, L.; Vicente, R.;
Kapdi, A. R. Angew. Chem. Int. Ed. 2009, 48, 9792. (b) Arockiam, P. B.; Bruneau, C.; Dixneuf,
P. H. Chem. Rev. 2012, 112, 5879. (c) Rouquet, G.; Chatani, N. Angew. Chem. Int. Ed. 2013, 52,
11726. For a recent book on C-H functionalization, see: (d) C-H Bond Activation in Organic
Synthesis; Li, J. J., Ed.; CRC Press: New York, 2015 and references cited therein.
(2) (a) From C-H to C-C Bonds: Cross-Dehydrogenative-Coupling; Li, C.-J., Ed.; Royal Society
of Chemistry: Cambridge, 2015. (b) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. (c)
Girard, S. A.; Knauber, T.; Li, C.-J. Angew. Chem. Int. Ed. 2014, 53, 74. (d) Topczewski, J. J.;
Sanford, M. S. Chem. Sci. 2015, 6, 70.
(3) (a) Shi, Z.; Schröder, N.; Glorius, F. Angew. Chem. Int. Ed. 2012, 51, 8092. (b) Wang, J.;
Liu, C.; Yuan, J.; Lei, A. Angew. Chem. Int. Ed. 2013, 52, 2256.
(4) (a) Jia, X.; Zhang, S.; Wang, W.; Luo, F.; Cheng, J. Org. Lett. 2009, 11, 3120. (b) Baslé, O.;
Bidange, J.; Shuai, Q.; Li, C.-J. Adv. Synth. Catal. 2010, 352, 1145. (c) Chan, C.-W.; Zhou, Z.;
Chan, A. S. C.; Yu, W.-Y. Org. Lett. 2010, 12, 3926. (d) Wu, Y.; Li, B.; Mao, F.; Li, X.; Kwong,
F. Y. Org. Lett. 2011, 13, 3258. (e) Li, C.; Wang, L.; Li, P.; Zhou, W. Chem. Eur. J. 2011, 17,
10208. (f) Zhou, B.; Yang, Y.; Li, Y. Chem. Commun. 2012, 48, 5163. (g) Matcha, K.;
ACS Paragon Plus Environment