Pd(II)-Catalyzed Denitrogenative and Desulfinative Addition of Arylsulfonyl Hydrazides with Nitriles

Article abstract of DOI:10.1021/acs.joc.8b00211

A Pd(II)-catalyzed denitrogenative and desulfinative addition of arylsulfonyl hydrazides with nitriles has been successfully achieved under mild conditions. This transformation is a new method for the addition reaction to nitriles with arylsulfonyl hydrazides as arylating agent, thus providing an alternative synthesis of aryl ketones. The reported addition reaction is tolerant to many common functional groups, and works well in the presence of electron-donating and electron-withdrawing substituents. Notably, the reported denitrogenative and desulfinative addition was also appropriate for alkyl nitriles, making this newly developed transformation attractive.

Full text of DOI:10.1021/acs.joc.8b00211

Subscriber access provided by UNIV OF DURHAM
Pd(II)-catalyzed Denitrogenative & Desulfinative
Addition of Arylsulfonyl Hydrazides with Nitriles
Mengting Meng, Liangfeng Yang, Kai Cheng, and Chenze Qi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00211 • Publication Date (Web): 05 Mar 2018
Downloaded from http://pubs.acs.org on March 5, 2018
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 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 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.
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 35
The Journal of Organic Chemistry
1
2
3
4
5
6
Pd(II)-catalyzed Denitrogenative & Desulfinative Addition of
Arylsulfonyl Hydrazides with Nitriles
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
Mengting Meng, Liangfeng Yang, Kai Cheng* and Chenze Qi
Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process,
Shaoxing University, 312000, Shaoxing, People’s Republic of China,
chengkai@usx.edu.cn. Fax:+86ꢀ575ꢀ88345682; Tel: +86ꢀ575ꢀ88345682.
Abstracts
A Pd(II)ꢀcatalyzed denitrogenative & desulfinative addition of arylsulfonyl hydrazides with
nitriles has been successfully achieved under mild conditions. This transformation is a new
method for the addition reaction to nitriles with arylsulfonyl hydrazides as arylating agent, thus
providing an alternative synthesis of aryl ketones. The reported addition reaction is tolerant to
many common functional groups, and work well in the presence of electronꢀdonating and
electronꢀwithdrawing substituents. Notably, the reported denitrogenative & desulfinative addition
was also be appropriate for alkyl nitriles, making this newly developed transformation attractive.
Keywords: denitrogenative & desulfinative addition, arylsulfonyl hydrazides,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 35
1
2
3
4
Pd(II)ꢀcatalyzed, addition with nitriles, synthesis of aryl ketones
5
6
7
8
9
Introduction
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
The aryl ketone moiety is one of the most fundamental and common building blocks occurring
in many pharmaceuticals, fragrances, natural products and synthetic biologically active
molecules.1 Aryl ketones are widely regarded as a privileged skeleton with broad pharmaceutical
activities, including neuroprotective drug (Nizofenone), antiarrhythmic (Pitofenone),
hypolipidemic (Fenofibrate), antitussive (Morclofone), uricosuric (Benzarone, Tienilic acid),
anxiolytic (Indiplon), antiꢀinflammatory (Suprofen, Ketorolac), NSAID (Amtolmetin guacil),
antiseptic (Pyoluteorin), antihelmintic (Flubendazole), antineoplastic (Nocodazole),
phosphodiesterase inhibitor (Piroximone), anticancer (ITE) and antitumor (Topsentin).(Scheme 1)
Scheme 1 Arylketone Skeletons in Drug Molecule
Classical routes to synthesize aryl ketones mainly rely on the Friedel–Crafts acylation of
ACS Paragon Plus Environment

Page 3 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
aromatic compounds in the presence of strong Lewis acids such as corrosive AlCl3, although the
reaction sometimes fails with electronꢀdeficient arenes and suffer from low functional group
tolerance generally yields the desired products as isomeric mixtures.2 The reactions of
stoichiometric organometallic compounds with acid chlorides, or Weinreb amides are also popular
and wellꢀknown for the preparation of ketones, provides us with an protocol for the synthesis of
aryl ketones.3 However, the poor functional group tolerance and strict handling requirement of the
organometallic reagents limits their applications and thus there is a need for cleaner, milder and
catalytic alternatives.4 Consequently, it continues to inspire the development of methods for the
construction of this structural element. During the last decade, transition metal catalysts have been
utilized for the synthesis of many compounds, and transitionꢀmetalꢀcatalyzed reactions provide
many opportunities for the synthesis of aryl ketones.5
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
Nitriles are normally very stable and widely commercially available. On the other hand,
transformations of nitriles play an important role in both the laboratory and industry due to their
wellꢀrecognized chemical versatility. The nucleophilic addition of organometallic reagents to
nitriles is an old and wellꢀknown reaction for ketone preparation. However, the nitrile group is
generally inert in organometallic reactions, and thus acetonitriles or benzonitriles usually
participate as solvents or ligands in transitionꢀmetalꢀcatalyzed coupling reactions.6 Among them, it
is an attractive and useful synthetic method for preparing aryl ketones from aryl halides and
nitriles through selective addition and subsequent in situ hydrolysis. In recent years, the
transitionꢀmetalꢀcatalyzed addition reaction has resulted in great progress in the synthesis of aryl
ketones from nitriles. The addition of arylpalladium species to the cyano group, pioneered by the
Larock group7 and elegantly employed in recent years,8 provided a conceptual basis for this
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 35
1
2
3
4
palladiumꢀcatalyzed approach.
5
6
7
8
9
Arylsulfonyl hydrazides are multipurpose and readily accessible intermediates in organic
synthesis, which are more airꢀstable than sulfonyl chlorides, can be synthesized directly from the
reaction of hydrazine hydrates with arylsulfonyl chloride.9 In general, they exist as solids that are
noncorrosive, compatible with water, and free of unpleasant odor. The electrophiles avoid the
production of undesired halideꢀcontaining byproducts and hence are more environmentally
desirable. Arylsulfonyl hydrazides are good crossꢀcoupling partners for ready generation of
reactive diazo compounds,10 as sulfonyl sources in organic synthesis.11 Arylsulfonyl hydrazides
can also react with carbon nucleophilic reagents by I2 to form various C–S bonds as sulfenylation
reagents.12 Recently, these compounds have also successfully been used as aryl sources via
desulfitation–denitrogenation have also been used in desulfinative crossꢀcoupling reactions.13
Desulfinative reactions not only produce sulfur dioxide as their main byproduct, but the loss of
gaseous SO2 is also the main driving force of desulfinative processes.14 In order to achieve greener,
more sustainable chemistry, this gas should not be wasted but rather recycled, possibly as the
feedstock for another process.15
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
Nowadays, arylsulfonyl hydrazides have been acted as arylating agents under desulfinative
processes (Scheme 2), mostly by direct CꢀH arylation of heteroarenes16 (such as benzoxazole,
indole, indolizine, caffeine), and crossꢀcoupling reaction17 (such as Sonogashira, Suzuki, Hiyama,
Heck, iodination and homocoupling). However, the desulfinative addition with arylsulfonyl
hydrazides was under development. The only example was reported by Deng et al.18 for
desulfinative conjugate addition of unsaturated carbonyl compounds. In continuing with our
interest in desulfinative coupling and addition with nitriles,19 herein we reported the first example
ACS Paragon Plus Environment

Page 5 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
of desulfinative addition of nitriles with arylsulfonyl hydrazides with good to excellent efficiency.
Both aryl and alkyl nitriles could afford corresponding aryl ketones in high yields.
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 2 Pdꢀcatalyzed denitrogenative & desulfinative reaction of arylsulfonyl hydrazides
Results and Discussion
Our studies commenced by evaluating the feasibility of the desulfinative addition reaction with
the investigation of reaction parameters with phenylsulfonyl hydrazides and benzonitrile in the
presence of active cationic Pd(II) species. The use of Pd(OAc)2 was explored in DMSO with 1
equiv H2O at 80oC under air in the presence of various ligands used previously in analogous
Pdꢀcatalyzed transformations (Table 1). Unsurprisingly, the phosphine ligands (PPh3, dppf,
BINAP), which has been recognized as a weakly coordinating promoter in desulfinative reaction,
failed to generate the desired product (Table 1, 1a-1c). To our delight, 62% yield of the desired
desulfinative addition product was found using 3 mol% of tetramethylethaneꢀ1,2ꢀdiamine
(TMEDA) as ligand (Table 1, 1d). A series of diamine ligands, including 1,2ꢀdiamine,
1,2ꢀdiphenylethaneꢀ1,2ꢀdiamine and benzeneꢀ1,2ꢀdiamine, was subsequently tested, and each of
these
catalysts
was
less
effective
than
TMEDA
(Table
1,
1e-1g).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 35
1
2
3
4
5
6
7
8
9
4,4,4',4'ꢀTetramethylꢀ4,4',5,5'ꢀtetrahydroꢀ2,2'ꢀbioxazole was ineffective to this transformation
(Table 1, 1h). To our delight, the application of bpy ligand (2,2’ꢀbipyridine) increased the yields
to 71% (Table 1, 1i). A screen of various phenꢀtype ligands, such as 1,10ꢀphenanthroline (phen),
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
4,7ꢀdimethoxyꢀ1,10ꢀphenanthroline,
4,7ꢀdiphenylꢀ1,10ꢀphenanthroline,
4,7ꢀdichloroꢀ1,10ꢀphenanthroline and 2,2'ꢀbiquinoline (bq), revealed bq was the best choice (Table
1, 1j-1n). In genaral, the use of a ligand is essential to obtain synthetically useful yield of biphenyl
ketone from the desulfinative addition reaction. Additionally, no desired product is obtained in the
absence of any ligands.
Table 1 Ligand selection of the desulfinative addition reaction a
Pd(OAc)2 (2 mol%)
O
Ligand (3 mol%)
O
N C
S NHNH2
O
H2O
DMSO
80oC, 6h
Ph
Ph
N
N
PPh3
dppf
BINAP
H2N
NH2
H2N
NH2
1d 62%
1a 0%
1c 0%
1e 28%
1b 0%
1f 38%
O
N
O
N
N
N
N
N
H2N
NH2
1h 43%
1i 74%
1g 50%
1j 83%
MeO
OMe Ph
Ph
Cl
Cl
N
N
N
N
N
N
N
N
1k 87%
1l 78%
1n 92%
1m 84%
a Reaction conditions: phenylsulfonyl hydrazide (1.1 mmol), benzonitrile (1.0 mmol), Pd(OAc)2 (2 mol%),
ligand (3 mol%), H2O (2.0 mmol), DMSO (2 mL), 80 oC, 6 h. Isolated yields.
Encouraged by the aforementioned results, other reaction conditions were investigated,
including the choice of catalyst and solvent. The results are summarized in Table 2. We initially
ACS Paragon Plus Environment

Page 7 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
examined palladium, ruthenium, and rhodium catalysts, respectively, using phenylsulfonyl
hydrazide and benzonitrile as our standard substrates and bq as the ligand. The reactions were
carried out in DMSO with 1 equiv H2O at 80 °C for 6 h. It was shown that Rh and Ru complex are
not effective for this reaction (Table 2, entries 1 and 2). The reaction failed to proceed in the
absence of palladium catalyst (Table 1, entry 3), suggesting that palladium catalyst is very crucial
for the formation of benzophenone compound. As detailed in Table 2, the optimal conditions for
the desulfinative addition can be applied toward the use of other palladium catalysts. Application
of Pd(dba)2 as a catalyst yielded traces of desired product (Table 2, entry 4). It was observed that
most of the Pd(II) catalysts could successfully promote the reaction (Table 2, entries 5−12).
Therefore, PdCl2, PdBr2 and PdI2 in combination with bq was applied affording benzophenone in
yields varying between 72% and 82% (Table 2, entries 5ꢀ7). It should be noted that Pd(TFA)2 and
Pd(OTf)2 were less effective than Pd(OAc)2 for this reaction (Table 2, entries 8−10). Among the
Pd(II) catalysts tested, Pd(OAc)2 was the most effective affording the addition product in 92%
yield (Table 2, entry 10). The introduction of various palladium with nitrogen ligands
(Pd(CH3CN)2Cl2 and Pd(PhCN)2Cl2) didn’t increased the yields (Table 2, entries 11–12). Various
solvents were screened, and the results revealed that aprotic solvent is the better choice for the
reaction (Table 2, entries 13−15). Although many traditional solvents have been tested, no better
results were obtained (Table 2, entries 16–18). Only a trace amount of product was detected with
other solvent, such as EA, hexane and DCM (Table 2, entries 19–21). Unfortunately, the desired
product was not obtained in water (Table 2, entry 22). Moreover, the yield was slightly decreased
when the reaction was performed in DMSO with a lower or higher amount of additional water
(Table 2, entries 23–24). Among these, DMSO was determined optimum, and benzophenone was
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 8 of 35
1
2
3
4
isolated in 92% yield.
5
6
Table 2 Desulfinative addition of phenylsulfonyl hydrazides with benzonitrile with various
7
8
9
catalysts in various solvents 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
1
catalyst (in DMSO)
RuCl2(PPh3)3
RhCl(PPh3)3
ꢀ
yield (%) b
entry
13
14
15
16
17
18
19
20
21
22
23
24
Solvent (with Pd(OAc)2)
yield (%) c
ꢀ
DMF
88
81
73
53
45
60
<5
<5
<5
ꢀ
2
ꢀ
DMA
acetone
1,4ꢀdioxane
THF
3
ꢀ
4
Pd(dba)2
<5
77
82
72
81
86
92
83
78
5
PdCl2
6
PdBr2
DME
7
PdI2
EA
8
Pd(TFA)2
Pd(OTs)2
Pd(OAc)2
Pd(CH3CN)2Cl2
Pd(PhCN)2Cl2
hexane
DCM
9
10
11
12
H2O
DMSO
DMSO
77 d
84 e
a Reaction conditions: phenylsulfonyl hydrazide (1.1 mmol), benzonitrile (1.0 mmol), bq (3 mol%), 80 oC,
6 h. Isolated yields. catalyst (2 mol%), H2O (2.0 mmol), DMSO (2 mL). c Pd(OAc)2 (2 mol%), H2O (2.0
b
mmol), solvent (2 mL).d Pd(OAc)2 (2 mol%), H2O (1.0 mmol), DMSO (2 mL). e Isolated yields. Pd(OAc)2
ACS Paragon Plus Environment

Page 9 of 35
The Journal of Organic Chemistry
1
2
3
4
(2 mol%), H2O (4.0 mmol), DMSO (2 mL).
5
6
7
8
9
Furthermore, considerable efforts have been made to test the substrate scope of this reaction
under the optimized reaction conditions. We applied this catalytic system to various arylsulfonyl
hydrazides with benzonitrile, and this reaction showed good compatibility with different groups
on aryl rings (Table 3). Electronꢀrich, electronꢀneutral, and electronꢀdeficient arylsulfonyl
hydrazides afford the desired products in modest to good yields (Table 3, 3a-3e). The
transformation is compatible with a number of synthetically versatile functional groups including
methoxy, fluoro, nitro, and trifluoromethyl. Position varied methyl and chloro phenylsulfonyl
hydrazides with paraꢀ, metaꢀ and orthoꢀsubstitution also couple with benzonitrile to afford the
corresponding diaryl ketone products in good yields (Table 3, 3f-3k). In general, the efficiency of
these reactions is attenuated relative to those with high steric hindrance. Treatment of highly steric
hindrance permethyl phenylsulfonyl hydrazides also provided the desired product in 73% yield
(Table 3, 3l). Notably, when the pꢀbromo phenylsulfonyl hydrazides is used, corresponding
desulfinative addition product is obtained in high yield, suggesting that the bromide leaving group
in the electrophile could survived and the relative reactivity toward desulfinative addition over
traditional coupling methods (Table 3, 3m). Heteroarylꢀsubstituted sulfonyl hydrazides led to a
slightly lower yield of the desired products (Table 3, 3n-3o).
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
Table 3 Scope of desulfinative addition with various arylsulfonyl hydrazides a
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 35
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
a Reaction conditions: arylsulfonyl hydrazide (1.1 mmol), benzonitrile (1.0 mmol), Pd(OAc)2 (2 mol%), bq (3
mol%), H2O (2.0 mmol), DMSO (2 mL), 80 oC, 6 h. Isolated yields.
Having explored the preliminary scope for the desulfinative addition of various arylsulfonyl
hydrazide, we next examined the reaction of phenylsulfonyl hydrazide with other aryl nitriles
(Table 4). Electronꢀdeficient, electronꢀrich, and moderately electronꢀdeficient aryl nitriles couple
with phenylsulfonyl hydrazide to afford the products in good to excellent yields (Table 4, 4a-4e).
In addition, orthoꢀ and metaꢀsubstituted aryl nitriles could also be well tolerated, generating the
desired coupling products in moderate to good yields (Table 4, 4f-4g). metaꢀTrifluoromethyl
disubstituted benzonitrile also participate effectively in this desulfinative reaction (Table 4, 4h).
The tolerance of the iodo group is especially significant, as successive functionalꢀgroup
transformations are hopeful (Table 4, 4i). Notably, the naphthalene nitrile also underwent
Pdꢀcatalyzed addition method, as did reactions of heteroaromatic nitrile was also proceeded
smoothly (Table 4, 4j-4k). The reaction of multiple fluoro substituted benzonitriles with
phenylsulfonyl hydrazide was next examined. Both 2,6ꢀdifluoro and 2,5ꢀdifluoro benzonitriles
ACS Paragon Plus Environment

Page 11 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
couple with phenylsulfonyl hydrazide to afford the desired products with comparable efficiencies
(Table 4, 4l-4m). However, the efficiency of the reactions using the perfluoro benzonitriles is
lower than that with trifluoro substituted and difluoro substituted substrates (Table 4, 4n-4o).
Table 4 Scope of desulfinative addition with various aryl nitriles 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
a Reaction conditions: phenylsulfonyl hydrazide (1.1 mmol), aryl nitrile (1.0 mmol), Pd(OAc)2 (2 mol%), bq (3
mol%), H2O (2.0 mmol), DMSO (2 mL), 80 oC, 6 h. Isolated yields.
Inspired by the above excellent results, we set out to explore the desulfinative addition of alkyl
nitriles. We begin our research by investigating the reaction of phenyl sulfonyl hydrazides with
2ꢀphenylacetonitrile in DMSO with H2O by using Pd(OAc)2 as catalyst and the desired product
was obtained in 33% yield. In order to improve the reaction yield, we attempted to optimized the
catalysts, ligands, solvents to enhance the reaction efficiency. Thus, we finished the optimization
of this challenging reaction with Pd(OAc)2/phen catalysts and H2O additive, in DMF solvents at
100oC (Table 5, entry 1). Table 5 illustrates a preliminary scope for the reaction of various alkyl
nitriles with phenylsulfonyl hydrazide. Importantly, 87% yield of product is obtained with
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 35
1
2
3
4
5
6
7
8
9
3ꢀoxobutanenitrile under the reaction conditions (Table 5, entry 2). Structurally varied alkyl
nitriles were couple with phenylsulfonyl hydrazide to afford the corresponding aryl ketone
products in modest to good yields (Table 5, entries 3ꢀ6). The reactions of the branched substituted
nitriles with phenylsulfonyl hydrazide were also explored and compared to the analogous
reactions with linear alkyl nitriles. Notably, for substituent, the yield was slightly enhanced with
gradually increasing the size of the substituent from Et, nꢀBu to iꢀPr and finally to cyclopentyl.
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
Table 5 Scope of desulfinative addition of phenylsulfonyl hydrazides with various alkyl nitriles
a
entry
1
alkyl nitrile
product
yield (%) b
90
2
3
4
5
87
75
82
79
CN
ACS Paragon Plus Environment

Page 13 of 35
The Journal of Organic Chemistry
1
2
3
4
O
6
83
5
6
7
8
9
a
Reaction conditions: phenylsulfonyl hydrazide (1.1 mmol), nitrile (1.0 mmol), Pd(OAc)2 (2
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
mol%), phen (3 mol%), H2O (2.0 mmol), DMF (2 mL), 100 oC, 6 h. b Isolated yields.
The subsequent solvent examination showed that a recent yield was observed without additional
solvent (DMF). The pꢀtoluenesulfonyl hydrazide coupling using CH3CN (2 mL) as the solvent
affords product pꢀtolylethanone (96%) in higher yield than product (71%) using CH3CN (2 equiv)
in DMF. Under the optimized reaction conditions, the scope of substituted arylsulfonyl hydrazides
was examined with Pd(OAc)2/phen catalysts and H2O (2 equiv) in CH3CN (Table 6). Functional
groups such as ethoxy, methoxy, nitro and fluoro were well tolerated under the optimal reaction
conditions (Table 6, 6a–6p). Notably, reaction with arylsulfonylhydrazide bearing NMe2 and SMe
group can also proceed smoothly to give the desired product in 85% and 87% yield and are not
affected by the N/S atom (Table 6, 6d–6e). It was found that arylsulfonyl hydrazides possessing
either electronꢀrich or electronꢀdeficient groups at the oꢀ, mꢀ or pꢀposition proceeded efficiently to
afford corresponding aryl ethanone in good to excellent yields (Table 6, 6f–6p). Furthermore,
cyano phenylsulfonyl hydrazide can also be a partner in the reaction to afford pꢀcyanoꢀphenyl
ethanone, with the cyano group untouched (Table 6, 6j). It should be noted that cleavage of
Cꢀhalogen bond was not observed during the reaction process (Table 6, 6q–6s). The substrate
scope of various steric hindered orthoꢀfunctionalized aryl sulfonyl hydrazides were explored, only
with slightly decrease of efficiency (Table 6, 6m, 6p, 6s). When mesitylene sulfonyl hydrazides
reacted with acetonitrile, slightly lower yields were obtained probably due to the steric effect of
the substituents (Table 6, 6i). In addition, 2ꢀnaphthyl substituted sulfonyl hydrazides was also
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 35
1
2
3
4
5
6
tested in the reaction and afforded the desired product 3af in 80% yield (Table 6, 6t).
Table 6 Scope of desulfinative addition of various arylsulfonyl hydrazides with acetonitrile a
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
a Reaction conditions: phenylsulfonyl hydrazide (1.0 mmol), Pd(OAc)2 (2 mol%), phen (3 mol%), H2O (2.0 mmol),
CH3CN (2 mL), 100 oC, 6 h. Isolated yields.
In order to understand the mechanism of the reaction, a series of control experiments were
carried out (Scheme 3). When the reaction was carried out under a nitrogen atmosphere, the
corresponding benzophenone was obtained in 82% yield (Scheme 3, Eq 1, A), which indicated
that the reaction didn’t required the presence of oxygen. Only 12% yield of desired product was
detected under typical procedure without 2 equiv water (Scheme 3, Eq 1, B). Also, the product
ACS Paragon Plus Environment

Page 15 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
formation was completely suppressed upon the addition of the 4A molecular sieve to the reaction
(Scheme 3, Eq 1, C). The 18Oꢀlabeling experiment was also performed to get more insights into
this reaction process (Scheme 3, Eq 1, D), indicating that the oxygen atom in the ketone molecule
was derived from H2O. Furthermore, when 4ꢀcyano phenylsulfonyl hydrazides was reacted with
benzonitrile or acetonitrile under the optimal conditions, the crossꢀcoupling products
4ꢀbenzoylbenzonitrile and 4ꢀacetylbenzonitrile were isolated, respectively without concomitant
formation of 4ꢀ(4ꢀ(sulfonyl)benzoyl)benzonitrile analogue as the product (Scheme 3, Eq 2 and Eq
3). No homoꢀcoupling products of 4ꢀcyano phenylsulfonyl hydrazides were detected by GC−MS
further. The phthalonitrile and isophthalonitrile substrates can be elaborated using myriad known
transformations of excessive phenylsulfonyl hydrazides for the synthesis of diverse dibenzoyl
motifs (Scheme 3, Eq 4). Another application of the presented desulfinative addition is its
potential for combination with Pdꢀcatalyzed Suzuki–Miyaura crossꢀcoupling to synthesize
(4ꢀbiphenylyl) (phenyl) methanone (Scheme 3, Eq 5). The Pdꢀcatalyzed desulfinative addition of
4ꢀiodobenzonitrile with phenylsulfonyl hydrazides, followed by consecutive Suzuki
crossꢀcoupling by the addition of PhB(OH)2, provides the 4ꢀbiphenylylꢀbenzophenone in the yield
of 83%. This approach has great potential in combination of Pdꢀcatalyzed
addition/Suzukiꢀcoupling by the sequential addition of reagents. Finally, the desulfinative addition
of both aryl nitriles and alkyl nitriles were scalable on gram scale, which showed the potential of
our palladiumꢀcatalyzed methods in the industrial application (Scheme 3, Eq 6 and Eq 7).
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 16 of 35
1
2
3
O
Pd(OAc)2
O
Pd(OAc)2
bq
4
5
6
7
8
9
bq, H2O N2
A
B
C
DMSO, 80oC
N
C
DMSO, 80oC
88%
O
22%
18O
Pd(OAc)2
Eq 1
Pd(OAc)2
O
S
H218O
bq
4A MS
bq
NHNH2
DMSO, 80oC
D
O
DMSO, 80oC
trace
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
GC yield (76%)
O
O
Pd(OAc)2
phen, H2O
O
S
CH3
O
N
N
C
NHNH2
NHNH2
CH3CN, 100oC
C
N
S
Eq 2
O
C
R
0%
N
O
S3a 86%
cross
homo R = NHNH2, OH
O
O
O
Pd(OAc)2
bq, H2O
C
S
O
O
Eq 3
DMSO, 80oC
C
N
S
C
R
N
O
N
C
0%
homo
S3b 83%
cross
R = NHNH2, OH
O
O
Pd(OAc)2
bq, H2O
78%
C
C
O
S
N
N
1 equiv
S3c
S3d
NHNH2
DMSO, 80oC
Eq 4
O
2.5 equiv
72%
C
C
N
N
O O
B(OH)2
K2CO3
1 equiv
O
Pd(OAc)2
bq, H2O
O
O
S
NHNH2
O
Eq 5
Ph
DMSO, 80oC
I
N
C
I
without isolation
S3e 83%
O
Pd(OAc)2
phen, H2O
O
CH3
Gram scale
S
NHNH2
Eq 6
Eq 7
CH3CN, 100oC
O
82%
6 mmol
O
Pd(OAc)2
bq, H2O
O
S
NHNH2
N
C
DMSO, 80oC
O
5.5 mmol
5 mmol
85%
Scheme 3 Control experiments and further application
Although the mechanistic details are yet to be ascertained, we propose a plausible catalytic
cycle for the palladiumꢀcatalyzed addition reaction of arylsulfonyl hydrazides with nitriles via
direct desulfitative and denitrificative coupling in the presence of bq is shown in Scheme 4.
ACS Paragon Plus Environment

Page 17 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Starting with the ligand coordinated Pd(II)ꢀcomplex, it is converted to Pd(II) species A and HOAc
by deprotonation with arylsulfonyl hydrazide. Intermediate A undergoes βꢀhydride elimination to
generated (arylsulfonyl)diazene and release HPdOAc at the same time. Subsequent displacement
of Pd(OAc)2 with (arylsulfonyl)diazene providing reactive Pd(II) intermediate B, arylpalladium(II)
intermediate C is formed through successive liberation of N2 and SO2 gas. The coordination of the
nitrile group with complex C to form Pd(II) complex D, which is probably a fast process given the
excess of nitrile. After 1,2ꢀcarbopalladation of the nitrile to form ketimine complex E, protonation
of the ketimine E by the HOAc afforded the free ketimine and a regenerated ligand coordinated
Pd(OAc)2 to complete the catalytic cycle. Finally, the formation of desired ketone product could
be achieved via the hydrolysis of the ketimine moiety. Additional water was enough for
hydrolysis.
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 18 of 35
1
2
3
4
Scheme 4 Possible Mechanism
5
6
7
Conclusion
8
9
We have developed a novel, highly efficient and airꢀstable method for the construction of aryl
ketone derivatives by the palladium catalyzed addition of arylsulfonyl hydrazides with nitriles in
good yields with high selectivities under aerobic and aqueous conditions. This denitrogenative &
desulfinative reaction proceeds with Pd(OAc)2/Nꢀligand catalysis with a broad scope of substrates,
and a series of aryl nitriles and alkyl nitriles can be utilized in this reaction. With the reaction, a
wide range of diaryl ketones and aryl alkyl ketones are synthesized in good to excellent yields.
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 Section
General
Reagents and solvents were used as it is obtained from commercial vendors. Products were
purified by column chromatography on silica gel (300–400 mesh) (ethyl acetate / petroleum ether
= v/v). 1H and 13C NMR spectra were obtained on Bruker–400 MHz spectrometers using
1
tetramethylsilane as internal standard in CDCl3. Chemical shifts of H NMR and 13C NMR are
reported as δ values relative to TMS and CDCl3 respectively. Chemical shifts were reported in
parts per million (ppm, δ). Proton coupling patterns are described as singlet (s), doublet (d), triplet
(t), quartet (q), multiplet (m), and broad resonances (br). HRMS (EI) data were collected on High
Resolution mass spectrometer (ion trap).
General experimental procedure for synthesis of aryl ketones
A mixture of phenylsulfonyl hydrazides (1.1 mmol), nitriles (1.0 mmol), Pd(OAc)2 (2 mol%), bq
(3 mol%) was stirred in DMSO (2 mL) and H2O (2 mmol) at 80oC for 6 hours at ambient
atmosphere. The reaction mixture was extracted by Et2O (5 mL) for three times. And then the
ACS Paragon Plus Environment

Page 19 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
organic phase was combined and evaporated under reduced pressure. The residue was purified on
a silica gel (300ꢀ400 mesh) column to afford the desired product (with petroleum and ethyl
acetate).
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
1
4-Methoxy-benzophenone (3a) White solid (E/P = 1/15), 192.9 mg (91%), m.p. 59–60 C. H
NMR ( 400 MHz, CDCl3, TMS ) δ 7.83 ( d, J = 8.4 Hz, 2 H ), 7.75 ( t, J = 7.6 Hz, 2 H ), 7.56 ( t, J
= 7.6 Hz, 1 H ), 7.45 ( t, J = 7.6 Hz, 2 H ), 6.95 ( d, J = 8.4 Hz, 2 H ), 3.88 ( s, 3 H ). 13C NMR
( 100 MHz, CDCl3 ) δ 195.6, 163.2, 138.3, 132.6, 132.0, 130.1, 129.8, 128.2, 113.6, 55.5. HRMS
(EI) Calcd for C14H12O2 (M+) 212.0837, Found 212.0843.
o
1
Benzophenone (3b) White solid (E/P = 1/20), 167.4 mg (92%), m.p. 46–48 C. H NMR ( 400
MHz, CDCl3, TMS ) δ 7.80 ( d, J = 8.4 Hz, 4 H ), 7.58 ( t, J = 7.6 Hz, 2 H ), 7.47 ( t, J = 8.0 Hz, 4
H ). 13C NMR ( 100 MHz, CDCl3 ) δ 196.9, 137.6, 132.4, 130.1, 128.3. HRMS (EI) Calcd for
C13H10O (M+) 182.0732, Found 182.0738.
4-Fluorobenzophenone (3c) White solid (E/P = 1/20), 166.1 mg (83%), m.p. 45–46 oC. 1H NMR
( 400 MHz, CDCl3, TMS ) δ 7.86 ( dd, J1 = 8.4 Hz, J2 = 5.0 Hz, 2 H ), 7.78 ( d, J = 7.2 Hz, 2 H ),
7.57 ( t, J = 7.2 Hz, 1 H ), 7.48 ( t, J = 7.6 Hz, 2 H ), 7.16 ( t, J = 8.4 Hz, 2 H ). 13C NMR ( 100
MHz, CDCl3 ) δ 195.3, 165.8 (d, J = 252 Hz), 137.5, 133.8 (d, J = 3.1 Hz), 132.7 (d, J = 9.0 Hz),
132.5, 129.9, 128.4, 115.5 (d, J = 21.5 Hz). HRMS (EI) Calcd for C13H9FO (M+) 200.0637, Found
200.0638.
4-Nitrobenzophenone (3d) Light yellow solid (E/P = 1/3), 190.7 mg (84%), m.p. 141–143 oC. 1H
NMR ( 400 MHz, CDCl3, TMS ) δ 8.34 ( d, J = 8.4 Hz, 2 H ), 7.94 ( d, J = 8.4 Hz, 2 H ), 7.81 ( d,
J = 7.2 Hz, 2 H ), 7.67 ( t, J = 7.6 Hz, 1 H ), 7.53 ( t, J = 7.2 Hz, 2 H ). 13C NMR ( 100 MHz,
CDCl3 ) δ 194.8, 149.8, 142.9, 136.3, 133.5, 130.7, 130.1, 128.7, 123.5. HRMS (EI) Calcd for
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 35
1
2
3
4
C13H9NO3 (M+) 227.0582, Found 227.0586.
5
6
7
8
9
4-Trifluoromethyl-benzophenone (3e) White solid (E/P = 1/3), 195.1 mg (78%), m.p. 117–118
oC. 1H NMR ( 400 MHz, CDCl3, TMS ) δ 7.89 ( d, J = 8.0 Hz, 2 H ), 7.81 ( d, J = 7.2 Hz, 2 H ),
7.75 ( d, J = 8.4 Hz, 2 H ), 7.63 ( t, J = 7.6 Hz, 1 H ), 7.52 ( t, J = 7.6 Hz, 2 H ). 13C NMR ( 100
MHz, CDCl3 ) δ 195.6, 140.7, 136.7, 133.7 ( dd, J1 = 64.6 Hz, J2 = 32.6 Hz ), 133.1, 130.2 ( d, J =
3.8 Hz ), 128.5, 125.4 ( dd, J1 = 7.2 Hz, J2 = 3.6 Hz ), 123.7 ( d, J= 271.2 Hz ). HRMS (EI) Calcd
for C14H9F3O (M+) 250.0605, Found 250.0602.
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
4-Methylbenzophenone (3f, 4c) White solid (E/P = 1/20), 182.3 mg (93%) for 3f and 184.3 mg
(94%) for 4c), m.p. 55–56 oC. 1H NMR ( 400 MHz, CDCl3, TMS ) δ 7.80 ( d, J = 6.8 Hz, 2 H ),
7.74 ( d, J = 8.0 Hz, 2 H ), 7.57 ( t, J = 8.0 Hz, 1 H ), 7.48 ( t, J = 7.2 Hz, 2 H ), 7.29 ( d, J = 8.0
Hz, 2 H ), 2.45 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 196.5, 143.3, 138.0, 134.9, 132.2, 130.3,
130.0, 129.0, 128.2, 21.7. HRMS (EI) Calcd for C14H12O (M+) 196.0888, Found 196.0893.
3-Methyl-benzophenone (3g) Colorless oil (E/P = 1/15), 170.5 mg (87%). 1H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.80 ( d, J = 7.2 Hz, 2 H ), 7.63 ( s, 1 H ), 7.58 ( d, J = 7.2 Hz, 2 H ), 7.49 ( t, J =
7.6 Hz, 2 H ), 7.33ꢀ7.41 (m, 2 H ), 2.42 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 197.1, 138.2,
137.7, 137.6, 133.3, 132.4, 130.5, 130.1, 128.3, 128.1, 127.4, 21.4. HRMS (EI) Calcd for C14H12O
(M+) 196.0888, Found 196.0883.
1
2-Methylbenzophenone (3h) Colorless oil (E/P = 1/20), 158.8 mg (81%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.81 ( d, J = 8.4 Hz, 2 H ), 7.60 ( t, J = 7.6 Hz, 1 H ), 7.48 ( t, J = 7.6 Hz, 2 H ),
7.41 ( t, J = 7.2 Hz, 1 H ), 7.24ꢀ7.34 ( m, 3 H ), 2.35 (s, 3H). 13C NMR ( 100 MHz, CDCl3 ) δ
198.7, 138.6, 137.7, 136.8, 133.1, 131.0, 130.2, 130.1, 128.52, 128.47, 125.2, 20.0. HRMS (EI)
Calcd for C14H12O (M+) 196.0888, Found 196.0882.
ACS Paragon Plus Environment

Page 21 of 35
The Journal of Organic Chemistry
1
2
3
4
4-Chloro-benzophenone (3i, 4d) White solid (E/P = 1/15), 183.7 mg (85%) for 3i and 190.1 mg
5
6
o
1
(88%) for 4d, m.p. 75–76 C. H NMR ( 400 MHz, CDCl3, TMS ) δ 7.77 ( t, J = 7.2 Hz, 4 H ),
7.60 ( t, J = 7.2 Hz, 1 H ), 7.50 ( t, J = 8.0 Hz, 2 H ), 7.46 ( d, J = 8.8 Hz, 2 H ). 13C NMR ( 100
MHz, CDCl3 ) δ 197.6, 138.9, 137.2, 135.8, 132.7, 131.5, 130.0, 128.7, 128.4. HRMS (EI) Calcd
for C13H9ClO (M+) 216.0342, Found 216.0347.
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
3-Chloro-benzophenone (3j) White solid (E/P = 1/15), 185.8 mg (86%), m.p. 83–85 oC. 1H NMR
( 400 MHz, CDCl3, TMS ) δ 7.79 ( d, J = 6.8 Hz, 2 H ), 7.78 ( s, 1 H ), 7.67 ( d, J = 6.8 Hz, 1 H ),
7.62 ( t, J = 7.2 Hz, 1 H ), 7.56 ( d, J = 8.0 Hz, 1 H ), 7.50 ( t, J = 7.6 Hz, 2 H ), 7.42 ( t, J = 8.0 Hz,
1 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 195.3, 139.2, 136.9, 134.6, 132.9, 132.4, 130.1, 129.9,
129.7, 128.5, 128.2. HRMS (EI) Calcd for C13H9ClO (M+) 216.0342, Found 216.0335.
2-Chlorobenzophenone (3k) White solid (E/P = 1/20), 177.1 mg (82%), m.p. 43–45 oC. 1H NMR
( 400 MHz, CDCl3, TMS ) δ 7.81 ( d, J = 8.4 Hz, 2 H ), 7.60 ( t, J = 7.6 Hz, 1 H ), 7.41ꢀ7.49 ( m, 4
H ), 7.36ꢀ7.39 ( m, 2 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 195.3, 138.6, 136.5, 133.7, 131.3, 131.2,
130.1, 129.1, 128.6, 126.7. HRMS (EI) Calcd for C13H9ClO (M+) 216.0342, Found 216.0340.
2,3,4,5,6-Pentamethyl-benzophenone (3l) White solid (E/P = 1/20), 184.0 mg (73%), m.p. 136–
137 oC. 1H NMR ( 400 MHz, CDCl3, TMS ) δ 7.83 ( d, J = 7.2 Hz, 2 H ), 7.55 ( t, J = 7.6 Hz, 1
H ), 7.44 ( t, J = 7.6 Hz, 2 H ), 2.28 ( s, 3 H ), 2.21 ( s, 6 H ), 2.02 ( s, 6 H ). 13C NMR ( 100 MHz,
CDCl3 ) δ 202.0, 137.7, 135.6, 133.4, 132.9, 129.6, 129.0, 128.7, 17.6, 16.8, 16.0. HRMS (EI)
Calcd for C18H20O (M+) 252.1514, Found 252.1516.
o
1
4-Bromobenzophenone (3m) White solid (E/P = 1/15), 231.4 mg (89%), m.p. 80–82 C. H
NMR ( 400 MHz, CDCl3, TMS ) δ 7.77 ( d, J = 8.4 Hz, 2 H ), 7.58ꢀ7.69 ( m, 5 H ), 7.49 ( t, J =
7.6 Hz, 2 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 195.7, 137.1, 136.3, 132.7, 131.63, 131.61, 130.0,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 35
1
2
3
4
128.5, 127.6. HRMS (EI) Calcd for C13H9BrO (M+) 259.9837, Found 259.9832.
5
6
o
1
2-Benzoylthiophene (3n) White solid (E/P = 1/20), 144.8 mg (77%), m.p. 53–54 C. H NMR
7
8
9
( 400 MHz, CDCl3, TMS ) δ 7.86 ( d, J = 7.2 Hz, 2 H ), 7.72 ( d, J = 4.8 Hz, 1 H ), 7.64 ( d, J =
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
3.6 Hz, 1 H ), 7.59 ( t, J = 7.2 Hz, 1 H ), 7.48 ( t, J = 7.2 Hz, 2 H ), 7.16 ( t, J = 4.4 Hz, 1 H ). 13
C
NMR ( 100 MHz, CDCl3 ) δ 188.2, 143.6, 138.2, 134.9, 134.2, 132.3, 129.2, 128.4, 128.0. HRMS
(EI) Calcd for C11H8OS (M+) 188.0296, Found 188.0299.
3-Benzoylpyridine (3o) White solid (E/P = 1/15), 152.7 mg (83%), m.p. 40–42 oC. 1H NMR ( 400
MHz, CDCl3, TMS ) δ 8.99 ( s, 1 H ), 8.81 ( d, J = 7.6 Hz, 1 H ), 8.12 ( d, J = 8.0 Hz, 1 H ), 7.82
( d, J = 8.4 Hz, 2 H ), 7.64 ( t, J = 7.6 Hz, 1 H ), 7.44ꢀ7.54 ( m, 3 H ). 13C NMR ( 100 MHz,
CDCl3 ) δ 195.0, 152.8, 150.9, 137.2, 136.6, 133.2, 133.1, 130.0, 128.6, 123.4. HRMS m/z (ESI)
calcd for C12H10NO [M+H]+ 184.0757, found 184.0750.
o
1
4-Benzyloxy-benzophenone (4a) White solid (E/P = 1/20), 244.8 mg (85%), m.p. 83–85 C. H
NMR ( 400 MHz, CDCl3, TMS ) δ 7.82 ( d, J = 8.4 Hz, 2 H ), 7.75 ( t, J = 7.2 Hz, 2 H ), 7.55 ( t, J
= 7.6 Hz, 1 H ), 7.32ꢀ7.48 ( m, 7 H ), 7.03 ( d, J = 8.8 Hz, 2 H ), 5.14 ( s, 2 H ). 13C NMR ( 100
MHz, CDCl3 ) δ 195.5, 162.4, 138.3, 136.2, 132.6, 131.9, 130.4, 129.8, 128.7, 128.3, 128.2, 127.5,
114.4, 70.2. HRMS (EI) Calcd for C20H16O2 (M+) 288.1150, Found 288.1143.
4-(Dimethylamino)benzophenone (4b) White solid (E/P = 1/5), 196.6 mg (87%), m.p. 92ꢀ94 oC.
1H NMR ( 400 MHz, CDCl3, TMS ) δ 7.80 ( d, J = 9.2 Hz, 2 H ), 7.71 ( d, J = 8.4 Hz, 2 H ), 7.52
( t, J = 7.2 Hz, 1 H ), 7.44 ( t, J = 7.6 Hz, 2 H ), 6.66 ( d, J = 7.6 Hz, 2 H ), 3.06 ( s, 6 H ). 13C
NMR ( 100 MHz, CDCl3 ) δ 195.2, 153.3, 139.3, 132.8, 131.2, 129.5, 128.0, 124.7, 110.5, 40.1.
HRMS m/z (ESI) calcd for C15H16NO [M+H]+ 226.1226, found 226.1223.
o
1
3-Nitrobenzophenone (4e) Light yellow solid (E/P = 1/5), 186.2 mg (82%), m.p. 96–97 C. H
ACS Paragon Plus Environment

Page 23 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
NMR ( 400 MHz, CDCl3, TMS ) δ 8.62 ( s, 1 H ), 8.45 ( d, J = 8.0 Hz, 1 H ), 8.14 ( d, J = 8.0 Hz,
1 H ), 7.81 ( d, J = 7.2 Hz, 2 H ), 7.72 ( t, J = 7.6 Hz, 1 H ), 7.66 ( t, J = 7.6 Hz, 1 H ), 7.54 ( t, J =
7.6 Hz, 2 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 194.2, 148.1, 139.0, 136.3, 135.5, 133.4, 130.0,
129.7, 128.8, 126.7, 124.7. HRMS (EI) Calcd for C13H9NO3 (M+) 227.0582, Found 227.0586.
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
1
3,4-Dimethylbenzophenone (4f) White solid (E/P = 1/20), 188.9 mg (90%), m.p. 47–48 C. H
NMR ( 400 MHz, CDCl3, TMS ) δ 7.80 ( d, J = 8.0 Hz, 2 H ), 7.64 ( s, 1 H ), 7.53ꢀ7.61 ( m, 2 H ),
7.49 ( t, J = 7.6 Hz, 2 H ), 7.24 ( t, J = 8.0 Hz, 1 H ), 2.36 ( s, 3 H ), 2.34 ( s, 3 H ). 13C NMR ( 100
MHz, CDCl3 ) δ 196.7, 142.0, 138.1, 136.8, 135.3, 132.1, 131.2, 130.0, 129.5, 128.2, 128.1, 20.0,
19.8. HRMS (EI) Calcd for C15H14O (M+) 210.1045, Found 210.1040.
3,4-Dichlorobenzophenone (4g) White solid (E/P = 1/20), 207.5 mg (83%), m.p. 103–104 oC. 1H
NMR ( 400 MHz, CDCl3, TMS ) δ 7.90 ( s, 1 H ), 7.77 ( d, J = 6.8 Hz, 2 H ), 7.64 ( t, J = 8.0 Hz, 2
H ), 7.58 ( d, J = 8.0 Hz, 1 H ), 7.50 ( t, J = 8.0 Hz, 2 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 194.2,
137.2, 137.0, 136.7, 133.0, 131.8, 130.5, 129.9, 129.1, 128.6. HRMS (EI) Calcd for C13H8Cl2O
(M+) 249.9952, Found 249.9956.
3,5-Bis(trifluoromethyl)benzophenone (4h) White solid (E/P = 1/10), 241.7 mg (76%), m.p.
108–110 oC. 1H NMR ( 400 MHz, CDCl3, TMS ) δ 8.24 ( s, 2 H ), 8.10 ( s, 1 H ), 7.79 ( d, J = 7.6
Hz, 2 H ), 7.69 ( t, J = 7.6 Hz, 1 H ), 7.56 ( d, J = 7.6 Hz, 2 H ). 13C NMR ( 100 MHz, CDCl3 ) δ
193.6, 139.4, 135.9, 133.6, 132.0 ( dd, J1 = 67.2 Hz, J2 = 33.6 Hz ), 130.0, 129.8 ( d, J = 2.1 Hz ),
128.9 125.6 ( t, J = 3.9 Hz ), 124.3, 121.5 ( q, J = 271 Hz ). HRMS (EI) Calcd for C15H8F6O (M+)
318.0479, Found 318.0481.
4-Iodobenzophenone (4i) White solid (E/P = 1/20), 280.3 mg (91%), m.p. 101–103 C. 1H NMR
o
( 400 MHz, CDCl3, TMS ) δ 7.84 ( d, J = 8.4 Hz, 2 H ), 7.77 ( d, J1 = 7.6 Hz, 2 H ), 7.60 ( t, J =
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 35
1
2
3
4
5
6
7
8
9
7.2 Hz, 1 H ), 7.46ꢀ7.53 ( m, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 195.9, 137.6, 137.1, 136.9,
132.7, 131.5, 130.0, 128.4, 100.2. HRMS (EI) Calcd for C13H9IO (M+) 307.9698, Found
307.9692.
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
1
1-Naphthyl-benzophenone (4j) White solid (E/P = 1/15), 186.5 mg (80%), m.p. 76–78 C. H
NMR ( 400 MHz, CDCl3, TMS ) δ 8.10 ( d, J = 7.6 Hz, 1 H ), 8.00 ( d, J = 8.4 Hz, 1 H ), 7.91 ( d,
J = 7.2 Hz, 1 H ), 7.86 ( d, J = 8.4 Hz, 2 H ), 7.42ꢀ7.61 (m, 7 H ). 13C NMR ( 100 MHz, CDCl3 ) δ
198.1, 138.3, 136.3, 133.7, 133.3, 131.3, 131.0, 130.5, 128.48, 128.45, 127.8, 127.3, 126.5, 125.7,
124.4. HRMS m/z (ESI) calcd for C17H13O [M+H]+ 233.0961, found 233.0961.
o
1
2-Benzoylpyridine (4k) White solid (E/P = 1/15), 131.8 mg (72%), m.p. 42–43 C. H NMR
( 400 MHz, CDCl3, TMS ) δ 8.72 ( d, J = 4.8 Hz, 1 H ), 8.02ꢀ8.08 ( m, 3 H ), 7.89 ( t, J = 7.6 Hz, 1
H ), 7.59 ( d, J = 7.2 Hz, 1 H ), 7.48 ( t, J = 7.6 Hz, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 194.1,
155.1, 148.6, 137.1, 136.3, 133.0, 131.0, 128.2, 126.2, 124.6. HRMS (EI) Calcd for C12H9NO (M+)
183.0684, Found 183.0683.
2,6-Difluorobenzophenone (4l) White solid (E/P = 1/10), 167.9 mg (77%), m.p. 134–136 oC. 1H
NMR ( 400 MHz, CDCl3, TMS ) δ 7.80 ( d, J = 8.4 Hz, 2 H ), 7.64 ( t, J = 7.6 Hz, 1 H ), 7.52 ( t, J
= 7.6 Hz, 2 H ), 7.31 ( dt, J1 = 7.2 Hz, J2 = 2.4 Hz, 2 H ), 7.05 ( tt, J1 = 8.4 Hz, J2 = 2.4 Hz, 1 H ).
13C NMR ( 100 MHz, CDCl3 ) δ 193.9, 162.6 ( dd, J1 = 250 Hz, J2 = 11.6 Hz ), 140.6 ( t, J = 7.2
Hz ), 136.4, 133.2, 130.0, 128.6, 112.9 ( dd, J1 = 18.3 Hz, J2 = 7.4 Hz ), 107.7 ( t, J = 25.1 Hz ).
HRMS (EI) Calcd for C13H8F2O (M+) 218.0543, Found 218.0549.
2,5-Difluorobenzophenone (4m) White solid (E/P = 1/10), 187.5 mg (86%), m.p. 99–100 oC. 1H
NMR ( 400 MHz, CDCl3, TMS ) δ 7.84 ( d, J = 8.4 Hz, 2 H ), 7.62 ( t, J = 7.6 Hz, 1 H ), 7.48 ( d,
J = 7.6 Hz, 2 H ), 7.19ꢀ7.28 ( m, 2 H ), 7.11ꢀ7.17 ( m, 1 H ). 13C NMR ( 100 MHz, CDCl3 ) δ
ACS Paragon Plus Environment

Page 25 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
192.1, 159.7, 157.2 (d, J = 252 Hz), 136.8, 133.8, 129.8, 128.6, 128.1 ( dd, J1 = 17.2 Hz, J2 = 6.4
Hz ), 119.7 ( dd, J1 = 23.6 Hz, J2 = 8.6 Hz ), 117.8 ( dd, J1 = 24.8 Hz, J2 = 8.0 Hz ), 117.0 ( dd, J1 =
18.4 Hz, J2 = 7.2 Hz ). HRMS (EI) Calcd for C13H8F2O (M+) 218.0543, Found 218.0548.
3,4,5-Trifluorobenzophenone (4n) White solid (E/P = 1/10), 191.2 mg (81%), m.p. 121–123 oC.
1H NMR ( 400 MHz, CDCl3, TMS ) δ 7.78 ( d, J = 7.2 Hz, 2 H ), 7.66 ( t, J = 7.6 Hz, 1 H ), 7.54
( t, J = 8.0 Hz, 2 H ), 7.50 ( t, J = 7.2 Hz, 1 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 192.9, 152.2 ( dd,
J1 = 41.2 Hz, J2 = 12 Hz ), 149.7 ( dd, J1 = 40.8 Hz, J2 = 14 Hz ), 144.0 ( t, J = 62.4 Hz ), 141.4 ( t,
J = 61.6 Hz ), 136.2, 133.1, 129.8, 128.6, 114.6 ( dd, J1 = 64 Hz, J2 = 24.8 Hz ). HRMS (EI) Calcd
for C13H7F3O (M+) 236.0449, Found 236.0438.
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
2,3,4,5,6-Perfluoro-benzophenone (4o) White solid (E/P = 1/15), 190.4 mg (70%), m.p. 36–37
oC. 1H NMR ( 400 MHz, CDCl3, TMS ) δ 7.86 ( d, J = 7.6 Hz, 2 H ), 7.69 ( t, J = 7.6 Hz, 1 H ),
7.54 ( t, J = 7.6 Hz, 2 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 185.2, 135.9, 135.1, 129.7, 129.1.
HRMS (EI) Calcd for C13H5F5O (M+) 272.0261, Found 272.0265.
o
1
1,2-Diphenylethanone (T5-1) White solid (E/P = 1/20), 177.3 mg (90%), m.p. 55–57 C. H
NMR ( 400 MHz, CDCl3, TMS ) δ 8.01 ( d, J = 7.8 Hz, 2 H ), 7.54 ( t, J = 7.2 Hz, 1 H ), 7.44 ( t, J
= 7.2 Hz, 2 H ), 7.22ꢀ7.34 ( m, 5 H ), 4.28 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 197.6, 136.6,
134.6, 133.2, 129.5, 128.70, 128.67, 128.64, 126.9, 45.5. HRMS m/z (ESI) calcd for C14H13O
[M+H]+ 197.0961, found 197.0962.
Benzoylacetone (T5-2) Colorless oil (E/P = 1/30), 141.8 mg (87%). 1H NMR ( 400 MHz, CDCl3,
TMS ) δ 7.87 ( d, J = 7.2 Hz, 2 H ), 7.51 ( t, J = 7.2 Hz, 1 H ), 7.44 ( t, J = 7.2 Hz, 2 H ), 6.17 ( s,
2 H ), 2.19 ( s, 3 H ). 13C NMR (100 MHz, CDCl3 ) δ 193.8, 183.3, 134.9, 132.3, 128.8, 128.6,
127.0, 96.7, 25.8. HRMS m/z (ESI) calcd for C10H11O2 [M+H]+ 163.0754, found 163.0749.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 35
1
2
3
4
5
6
7
8
9
Propiophenone (T5-3) Colorless oil (E/P = 1/50), 101.2 mg (75%). 1H NMR ( 400 MHz, CDCl3,
TMS ) δ 7.90 ( d, J = 7.6 Hz, 2 H ), 7.48 ( t, J = 7.6 Hz, 1 H ), 7.38 ( t, J = 7.6 Hz, 2 H ), 2.93 ( q,
J = 7.2 Hz, 2 H ), 1.15 ( t, J = 7.2 Hz, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 200.6, 136.9, 132.8,
128.5, 127.9, 31.7, 8.2. HRMS m/z (ESI) calcd for C9H11O [M+H]+ 135.0804, found 135.0802.
Pentanophenone (T5-4) Colorless oil (E/P = 1/50), 133.7 mg (82%). 1H NMR ( 400 MHz, CDCl3,
TMS ) δ 7.94 ( d, J = 7.2 Hz, 2 H ), 7.53 ( t, J = 7.2 Hz, 1 H ), 7.42 ( t, J = 7.6 Hz, 2 H ), 2.95 ( t, J
= 7.6 Hz, 2 H ), 1.67ꢀ1.75 ( m, 2 H ), 1.37ꢀ1.43 ( m, 2 H ), 0.94 ( t, J = 7.2 Hz, 3 H ). 13C NMR
( 100 MHz, CDCl3 ) δ 200.5, 137.1, 132.8, 128.5, 128.0, 38.3, 26.5, 22.5, 13.9. HRMS m/z (ESI)
calcd for C11H15O [M+H]+ 163.1117, found 163.1109.
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
Isobutyrophenone (T5-5) Colorless oil (E/P = 1/50), 117.7 mg (79%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.95 ( d, J = 7.6 Hz, 2 H ), 7.53 ( t, J = 7.2 Hz, 1 H ), 7.44 ( t, J = 7.2 Hz, 2 H ),
3.55 ( m, 1 H ), 1.21 ( d, J = 6.8 Hz, 6 H ). 13C NMR (100 MHz, CDCl3 ) δ 204.4, 136.2, 132.8,
128.6, 128.3, 35.3, 19.1. HRMS m/z (ESI) calcd for C10H13O [M+H]+ 149.0961, found 149.0957.
1
Cyclopentyl(phenyl)methanone (T5-6) Colorless oil (E/P = 1/50), 145.3 mg (83%). H NMR
( 400 MHz, CDCl3, TMS ) δ 7.97 ( d, J = 7.2 Hz, 2 H ), 7.53 ( t, J = 7.2 Hz, 1 H ), 7.44 ( t, J = 7.2
Hz, 2 H ), 3.66ꢀ3.75 ( m, 1 H ), 1.86ꢀ1.94 ( m, 4 H ), 1.60ꢀ1.77 ( m, 4 H ). 13C NMR (100 MHz,
CDCl3 ) δ 202.8, 136.9, 132.7, 128.5, 128.4, 46.3, 30.0, 26.3. HRMS m/z (ESI) calcd for C12H15O
[M+H]+ 175.1117, found 175.1109.
1
4'-Ethoxyacetophenone (6a) Colorless oil (E/P = 1/30), 152.5 mg (93%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.79 ( d, J = 8.8 Hz, 2 H ), 6.77 ( d, J = 8.8 Hz, 2 H ), 3.94 ( q, J = 7.2 Hz, 2 H ),
2.41 ( s, 3 H ), 1.30 ( t, J = 7.2 Hz, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 196.5, 162.8, 130.4,
130.0, 114.0, 63.6, 26.1, 14.6. HRMS (EI) Calcd for C10H12O2 (M+) 164.0837, Found 164.0833.
ACS Paragon Plus Environment

Page 27 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
4'-Methoxyacetophenone (6b) Colorless oil (E/P = 1/30), 135.0 mg (90%). 1H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.86 ( d, J = 8.8 Hz, 2 H ), 6.86 ( d, J = 8.8 Hz, 2 H ), 3.78 ( s, 3 H ), 2.48 ( s, 3
H ). 13C NMR ( 100 MHz, CDCl3 ) δ 196.7, 163.4, 130.5, 130.2, 113.6, 55.4, 26.3. HRMS (EI)
Calcd for C9H10O2 (M+) 150.0681, Found 150.0689.
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'-Methoxyacetophenone (6c) Colorless oil (E/P = 1/30), 138.1 mg (92%). 1H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.38 ( d, J = 7.6 Hz, 1 H ), 7.33 ( s, 1 H ), 7.21 ( t, J = 8.0 Hz, 1 H ), 6.96 ( d, J =
7.2 Hz, 1 H ), 3.68 ( s, 3 H ), 2.43 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 197.6, 159.7, 138.3,
129.5, 120.9, 119.3, 112.3, 55.2, 26.5. HRMS (EI) Calcd for C9H10O2 (M+) 150.0681, Found
150.0677.
4'-Dimethylaminoacetophenone (6d) Colorless oil (E/P = 1/20), 138.6 mg (85%). 1H NMR ( 400
MHz, CDCl3, TMS ) δ 7.86 ( d, J = 8.4 Hz, 2 H ), 6.63 ( d, J = 8.0 Hz, 2 H ), 3.03 ( s, 6 H ), 2.50
( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 196.4, 153.4, 130.5, 125.3, 110.6, 40.0, 26.0. HRMS
(EI) Calcd for C10H13NO (M+) 163.0997, Found 163.0991.
1
4'-Methylthioacetophenone (6e) Colorless oil (E/P = 1/30), 144.4 mg (87%). H NMR ( 400
MHz, CDCl3, TMS ) δ 7.82 ( d, J = 8.0 Hz, 2 H ), 7.21 ( d, J = 8.0 Hz, 2 H ), 2.52 ( s, 3 H ), 2.47
( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 197.1, 145.9, 133.4, 128.7, 124.9, 26.4, 14.7. HRMS
(EI) Calcd for C9H10OS (M+) 166.0452, Found 166.0460.
1
4'-Methylacetophenone (6f) Colorless oil (E/P = 1/30), 128.6 mg (96%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.76 ( d, J = 6.8 Hz, 2 H ), 7.14 ( d, J = 7.2 Hz, 2 H ), 2.45 ( s, 3 H ), 2.30 ( s, 3
H ). 13C NMR ( 100 MHz, CDCl3 ) δ 197.6, 143.7, 134.6, 129.2, 128.4, 26.4, 21.5. HRMS (EI)
Calcd for C9H10O (M+) 134.0732, Found 134.0728.
1
3'-Methylacetophenone (6g) Colorless oil (E/P = 1/30), 152.5 mg (93%). H NMR ( 400 MHz,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 35
1
2
3
4
5
6
7
8
9
CDCl3, TMS ) δ 7.76 ( s, 1 H ), 7.74 ( d, J = 7.2 Hz, 2 H ), 7.36 ( d, J = 7.6 Hz, 1 H ), 7.33 ( t, J =
7.2 Hz, 1 H ), 2.57 ( s, 3 H ), 2.40 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 198.3, 138.3, 137.1,
133.9, 128.8, 128.4, 125.6, 26.7, 21.3. HRMS (EI) Calcd for C9H10O (M+) 134.0732, Found
134.0739.
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', 5'-Dimethylacetophenone (6h) Colorless oil (E/P = 1/30), 130.2 mg (93%). H NMR ( 400
MHz, CDCl3, TMS ) δ 7.55 ( s, 2 H ), 7.17 ( s, 1 H ), 2.55 ( s, 3 H ), 2.34 ( s, 6 H ). 13C NMR
( 100 MHz, CDCl3 ) δ 198.5, 138.1, 137.2, 134.7, 126.2, 26.7, 21.2. HRMS (EI) Calcd for
C10H12O (M+) 148.0888, Found 148.0895.
2', 4', 6'-Trimethylacetophenone (6i) Colorless oil (E/P = 1/30), 128.0 mg (79%). 1H NMR ( 400
MHz, CDCl3, TMS ) δ 6.82 ( s, 2 H ), 2.43 ( s, 3 H ), 2.27 ( s, 3 H ), 2.21 ( s, 6 H ). 13C NMR
( 100 MHz, CDCl3 ) δ 208.1, 140.0, 138.1, 132.2, 128.5, 32.1, 21.0, 19.0. HRMS (EI) Calcd for
C11H14O (M+) 162.1045, Found 162.1052.
1
3'-Cyanoacetophenone (6j) Colorless oil (E/P = 1/30), 124.7 mg (86%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 8.21 ( s, 1 H ), 8.16 ( d, J = 7.6 Hz, 2 H ), 7.82 ( d, J = 6.8 Hz, 1 H ), 7.61 ( t, J =
8.0 Hz, 1 H ), 2.62 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 195.9, 137.7, 136.0, 132.3, 132.0,
129.7, 117.9, 113.1, 26.6. HRMS (EI) Calcd for C9H7NO (M+) 145.0528, Found 145.0522.
1
4'-Fluoroacetophenone (6k) Colorless oil (E/P = 1/30), 117.3 mg (85%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.81 ( d, J = 8.4 Hz, 2 H ), 6.96 ( d, J = 8.4 Hz, 2 H ), 2.41 ( s, 3 H ). 13C NMR
( 100 MHz, CDCl3 ) δ 196.2, 165.5 (d, J = 251.8 Hz), 133.5 (d, J = 2.8 Hz), 130.8 (d, J = 9.1 Hz),
115.4 (d, J = 22.4 Hz), 26.2. HRMS (EI) Calcd for C8H7FO (M+) 138.0481, Found 138.0486.
1
3'-Fluoroacetophenone (6l) Colorless oil (E/P = 1/30), 124.2 mg (90%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.69 ( d, J = 8.0 Hz, 1 H ), 7.58 ( d, J = 9.6 Hz, 1 H ), 7.37ꢀ7.43 ( m, 1 H ),
ACS Paragon Plus Environment

Page 29 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
7.18ꢀ7.24 ( m, 1 H ), 2.55 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 196.7 (d, J = 2.5 Hz), 162.8
(d, J = 246.0 Hz), 139.1 (d, J = 5.2 Hz), 130.2 (d, J = 7.4 Hz), 124.1 (d, J = 5.2 Hz), 120.0 (d, J =
21.4 Hz), 114.8 (d, J = 22.2 Hz), 26.6. HRMS (EI) Calcd for C8H7FO (M+) 138.0481, Found
138.0489.
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
2'-Fluoroacetophenone (6m) Colorless oil (E/P = 1/30), 111.8 mg (81%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.79 ( t, J = 8.0 Hz, 1 H ), 7.44 ( q, J = 6.4 Hz, 1 H ), 7.79 ( t, J = 7.6 Hz, 1 H ),
7.05 ( t, J = 9.6 Hz, 1 H ), 2.55 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 195.6 (d, J = 3.0 Hz),
162.1 (d, J = 252.6 Hz), 134.6 (d, J = 8.6 Hz), 130.5 (d, J = 2.6 Hz), 125.6 (d, J = 2.7 Hz), 124.3
(d, J = 3.9 Hz), 116.6 (d, J = 23.7 Hz), 31.2 (d, J = 6.7 Hz). HRMS (EI) Calcd for C8H7FO (M+)
138.0481, Found 138.0474.
1
4'-Nitroacetophenone (6n) Colorless oil (E/P = 1/15), 135.3 mg (82%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 8.24 ( d, J = 8.8 Hz, 2 H ), 8.08 ( d, J = 8.4 Hz, 2 H ), 2.65 ( s, 3 H ). 13C NMR
( 100 MHz, CDCl3 ) δ 196.4, 150.3, 141.4, 129.3, 123.8, 26.9. HRMS (EI) Calcd for C8H7NO3
(M+) 165.0426, Found 165.0421.
1
3'-Nitroacetophenone (6o) Colorless oil (E/P = 1/15), 137.0 mg (83%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 8.69 ( s, 1 H ), 8.35 ( d, J = 7.2 Hz, 1 H ), 8.26 ( d, J = 8.4 Hz, 1 H ), 7.67 ( t, J =
8.0 Hz, 1 H ), 2.66 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 195.7, 148.3, 138.2, 133.9, 130.0,
127.3, 123.1, 26.7. HRMS (EI) Calcd for C8H7NO3 (M+) 165.0426, Found 165.0429.
1
2'-Nitroacetophenone (6p) Colorless oil (E/P = 1/15), 122.1 mg (74%). H NMR ( 400 MHz,
CDCl3, TMS ) δ 7.95 ( d, J = 8.0 Hz, 1 H ), 7.65 ( t, J = 7.2 Hz, 1 H ), 7.53 ( t, J = 8.0 Hz, 1 H ),
7.40 ( d, J = 7.6 Hz, 1 H ), 2.66 ( s, 3 H ). 13C NMR ( 100 MHz, CDCl3 ) δ 199.9, 145.8, 137.5,
134.3, 130.8, 127.4, 124.2, 29.9. HRMS (EI) Calcd for C8H7NO3 (M+) 165.0426, Found 165.0420.
ACS Paragon Plus Environment