Palladium-Catalyzed Ligand-Free Decarboxylative Coupling of α- Oxocarboxylic Acid with Aryl Diazonium Tetrafluoroborate: An Access to Unsymmetrical Diaryl Ketones

Article abstract of DOI:10.1021/acs.joc.8b01922

Diaryl ketones are of much importance in organic synthesis as versatile intermediates and in industry for their useful properties. A mild and efficient palladium-catalyzed traditional ligand-free decarboxylative coupling of aryl α-keto carboxylic acid with aryl diazonium fluoroborate has been developed. A series of unsymmetrical diaryl ketones has been synthesized in moderate to good yields using this procedure. A radical pathway involving the acyl radical has been suggested.

Full text of DOI:10.1021/acs.joc.8b01922

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Article
Palladium Catalyzed Ligand Free Decarboxylative
Coupling of #- Oxocarboxylic Acid with Aryl Diazonium
Tetrafluoroborate: An Access to Unsymmetrical Diaryl Ketones
Subir Panja, Pintu Maity, and Brindaban Chandra Ranu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01922 • Publication Date (Web): 25 Sep 2018
Downloaded from http://pubs.acs.org on September 25, 2018
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Palladium Catalyzed Ligand Free Decarboxylative Coupling of α-
Oxocarboxylic Acid with Aryl Diazonium Tetrafluoroborate: An Access to
Unsymmetrical Diaryl Ketones
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Subir Panja, Pintu Maity and Brindaban C. Ranu*
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur,
Kolkata – 700032, India
ocbcr@iacs.res.in.
Abstract. The diaryl ketones are of much importance in organic synthesis as versatile
intermediates and in industry for their useful properties. A mild and efficient palladium
catalyzed traditional ligand free decarboxylative coupling of aryl αꢀketo carboxylic acid with
aryl diazonium fluoroborate has been developed. A series of unsymmetrical diaryl ketones has
been synthesized in moderate to good yields using this procedure. A radical pathway involving
the acyl radical has been suggested.
Introduction. The diaryl ketones are of much importance in organic synthesis as well as in
pharmaceutical industry.1 They have wide applications as synthetic intermediates for the
preparation of many useful compounds including oximes, cyanohydrins, carbazones, acetals,
pinacols etc.2 They are found as important structural motifs in natural products, pharmaceuticals
(Figure 1), and functional materials.3 Thus, synthesis of these compounds is of continued
interest.
Me
Me
Cl
CO2
H
CO2H
CO2H
N
N
N
O
Me
Me
O
O
ketorolac
Tolmetin
Zomepiral
O
O
O
O
CO2
H
S
Cl
O
O
HO
Benzarone
O
N
O
Suprofen
Morclofone
O
O
O
O
O
O
OH
O
N
HN
N
N
O
NH
NH
N
H
NH
F
Flubendazole
Pitofenone
Topsentin
Figure 1: A few examples of aryl ketones having biological activity
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The classical method for the synthesis of aryl ketones involves FriedelꢀCrafts acylation of
arenes4 in the presence of a Lewis acid, AlCl3 which is corrosive. The other limitations of this
reaction are low yield or no reaction with electronꢀdeficient arenes, formation of isomeric
mixture of products, use of more than stoichiometric AlCl3 catalyst and generation of huge
waste.5 During last two decades transition metal catalyzed cross coupling reactions have
emerged as a powerful tool for the carbon ꢀ carbon bond formation6 and this process has been
successfully utilized for the synthesis of aryl ketones.7 The decarboxylative cross coupling of
carboxylates8aꢀ8d and αꢀoxocarboxylates8e with aryl halides/boronic acids/triflates using
Pd(II)/Cu(I) catalytic system in the presence of nitrogen/phosphorusꢀbased ligands for the
synthesis of unsymmetrical diaryl ketones has been introduced by Goossen’s group.8 A notable
merit of this reaction is the elimination of toxic metal waste as only carbon dioxide is produced
other than product. Since then, several methods based on this concept with variation of catalyst,
ligand and substrate have been reported.9
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In recent times, the transition metal catalyzed functionalization of a CꢀH bond directed by a
neighboring group is also of much interest as this method does not require prefunctionalization
of substrate and in addition, this process is relatively green being more atom economic.10 This
strategy has been successfully employed for the synthesis of diaryl ketones.11 However, one
serious limitation of this method is the introduction of a directing group prior to acylation and
difficulty in removing this group after reaction.12 More recently, this drawback has been
overcome by using a suitable ligand that activates the CꢀH bond toward functionalization. One
such report was the synthesis of diaryl ketone by the reaction of aldehyde and aryl halide using
palladium/picolinamide catalyst via CꢀH bond activation. However, the ligands are usually
expensive and the reactions are performed at elevated temperature.13
Hence, a more simple and efficient procedure for the synthesis of diaryl ketones is still
appreciated. Earlier methods based on decarboxylative coupling were reported using costly
ligands (Scheme 1). We report here a Pd catalyzed synthesis of diaryl ketones by the
decarboxylative coupling of αꢀketo carboxylic acid with aryl diazonium fluoroborate in the
absence of any traditional ligand (Scheme 2). The aryl diazonium fluoroborates are easily
prepared from aryl amines via diazotization.14 Earlier, aryl boronic acid, aryl halide and aryl
triflates which are relatively expensive, have been used for this type of reaction (Scheme 1),
while aryl amines which are cheap and readily available with varieties of substitutents, remained
unexplored .15
Scheme 1. Earlier methods for the synthesis of aryl ketone using ligands
Previous reports :
O
O
[Pd cat.]
oxidising agent
CO2K/H
X
ligand
X = -H, -Br, -Cl, -OTf,
-BF3K, -B(OH)2
O
O
O
Pd(PPh3)4
P-(p- tol)3
CO2H
CO
2
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Scheme 2. Present method for the synthesis of aryl ketones
5
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8
O
O
Pd(PhCN)2Cl2
(NH4)2S2O8
OH
F4BN2
R2
R1
R2
R1
DMF, 90 oC, Ar
10 h
O
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Results and Discussion
To optimize the reaction conditions, a series of experiments were performed with variation of
solvent, temperature, time, oxidizing agent, and catalyst for a representative reaction of 4ꢀ
methoxy diazonium fluoroborate and phenyl glyoxylic acid.
Among the various solvents investigated for this reaction, dimethyl formamide (DMF) produced
the best yield in the presence of bis(benzonitrile)palladium dichloride[Pd(PhCN)2Cl2] (5 mol %)
catalyst, (NH4)2S2O8 (1 equiv.) at 90 oC for 10 h (Table 1, entry 6). Dimethyl sulfoxide (DMSO)
Table 1. Standardization of reaction conditionsa
O
O
N2BF4
HO
catalyst, oxidant
solvent, temperature
time
O
MeO
MeO
Entry
Catalyst
Oxidant
Solvent
Temp.
(oC)
90
Yields
(%)
82
1
2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(OAc)2
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
K2S2O8
DMSO
Toluene
THF
90
42
3
90
38
4
CH3CN
DCE
90
46
5
90
18
6
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
90
91
7
90
77
8
Ag(OAc)
90
42
9b
10c
11
12d
13
14
15e
(NH4)2S2O8
(NH4)2S2O8
ꢀ
90
45
90
72
90
37
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
90
67
90
72
Pd(acac)2
90
83
Pd(PhCN)2Cl2
90
73
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16f
17
Pd(PhCN)2Cl2
NiCl2
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
90
90
90
90
50
80
rt
82
trace
trace
trace
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CoCl2 . 6 H2O
ꢀ
6
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19
8
9
20
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
PdCl2
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22
10
23g
24h
25i
26j
27k
28
90
90
90
90
90
90
90
67
43
63
72
82
75
29
Pd(CH3CN)2Cl2
84
a
Reaction conditions : Aryl diazonium fluoroborate (0.5 mmol), PhCOCO2H (1 mmol),
b
c
Pd(PhCN)2Cl2 (5 mol %), (NH4)2S2O8 (1 equiv.), solvent (3 mL). (NH4)2S2O8 (0.5 equiv.).
(NH4)2S2O8 (2.0 equiv.). d PhCOCO2H (1.0 equiv.). e Pd(PhCN)2Cl2 (10 mol %). f Pd(PhCN)2Cl2
(20 mol %). g reaction time 12 h. h reaction time 15 h. i with ligand SPhos. with ligand PPh3. k
j
under aerial condition.
is considerably effective (Table 1, entry 1) whereas toluene, tetrahydrofuran (THF), acetonitrile
(CH3CN), 1,2ꢀdichloro ethane (DCE) led to lower yields (Table 1, entries 2 ꢀ5). Reaction at
o
o
lower temperature (50 C and 80 C) reduced the yields further (Table 1, entries 20 and 21).The
reaction for longer time than 10 h also decreased the yield (Table 1, entries 23 and 24). Other
palladium salts such as Pd(OAc)2 and Pd(acac)2 are also effective (Table 1, entries 13 and 14). In
the absence of Pd catalyst the reaction was virtually negative (Table 1, entry 19). The other
metal salts, NiCl2 and CoCl2 did not initiate this reaction (Table 1, entries 17 and 18). Among the
oxidizing agents (NH4)2S2O8 (1 equivalent) provided better yield (Table 1, entry 6). It has been
observed that use of 0.5 equiv. and 2.0 equiv.of (NH4)2S2O8 did not make any improvement
(Table 1, entries 9 and 10). The oxidizing agent, K2S2O8 also led to considerably good yield
(Table 1, entry 7) but Ag(OAc) furnished lower yield (Table 1, entry 8). Without oxidizing
agent, the reaction gave very low yield (Table 1, entry 11). 5 Mol % of Pd(PhCN)2Cl2 provided
the best yield, while use of 10 mol % or 20 mol % reduced the yield (Table 1, entry 15, 16). The
reaction using ligands PPh3 and SꢀPhos (Table 1, entries 25 and 26) led to lower yields. The
reaction under aerial condition also provided reduced yield (Table 1, entry 27).
Thus, in a typical experimental procedure a mixture of aryl diazonium tetrafluoroborate and
phenyl glyoxylic acid in DMF solution was heated at 90 C in the presence of Pd(PhCN)2Cl2
catalyst with oxidizing agent (NH4)2S2O8 for a required period of time (monitored by TLC).
After the reaction was over DMF was evaporated and the residue was extracted with ethyl
o
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acetate. Purification of the crude product by column chromatography over silica gel furnished
the pure one.
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A wide range of substituted aryl diazonium fluoroborates were subjected to reaction with phenyl
glyoxylic acid by this procedure to produce the corresponding aryl ketones. The results are
summarized in Table 2. Both electron donating (ꢀ Me, ꢀEt, ꢀOMe) and electron withdrawing
groups (ꢀCN, ꢀNO2, ꢀCO2Me) bearing aryl diazonium fluoroborates underwent uniform reaction
with phenyl glyoxylic acid to provide the corresponding products (3b, 3c, 3d, 3f, 3g, 3o, 3p, 3q,
3r and 3s). Halogen containing aryl diazonium fluoroborates were also compatible for this
reaction (3h, 3i, 3j, 3k, 3l, 3m and 3n) and needless to say, the presence of halogens provides
scope for further functionalization.
Aryl diazonium fluoroborates containing sterically hindered 2,6ꢀdimethyl group, biologically
active functional group such as –F, ꢀCF3 and bicyclic moiety, naphthalene also reacted smoothly
with phenyl glyoxylic acid to produce the corresponding products (Table 2, 3e, 3h, 3i, 3j, 3l, 3t
and 3u). Several functional groups such as ꢀOMe, ꢀCN, ꢀNO2, ꢀCO2Me, are compatible with the
reaction conditions (Table 2, 3g, 3oꢀ3s). The substitution of electron donating and electron
withdrawing groups on the phenyl ring of aryl diazonium fluoroborates did not have any
appreciable influence on the outcome of the reaction.
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Table 2. Pd catalyzed synthesis of unsymmetrical diaryl ketones from substituted
aryl diazonium fluoroborates and phenyl glyoxylic acida, b
O
O
Pd(PhCN)2Cl2
(NH4)2S2O8
F4BN2
OH
R
R
O
DMF, 90 oC, Ar
10 h
O
O
O
O
O
CH3
H3C
CH3
H3C
3a, 87%, 10 h
O
3b, 88%, 10 h
CH3
3e, 69%, 11 h
3c, 76%, 10 h
3d, 81%, 10 h
O
O
O
O
F
F
CH2CH3
OMe
F
H3C
3h, 75%, 11 h
3j, 82%, 10 h
3g, 91%, 10 h
O
3f, 88%, 10 h
O
3i, 72%, 10 h
O
O
O
CH3
Cl
Cl
Cl
Br
CN
3n, 86%, 10 h
O
Cl
CF3
3o, 75%, 11 h
O
3m, 68%, 11 h
3l, 79%, 10 h
3k, 81%, 10 h
O
O
O
CO2Me
3s, 71%, 12 h
F3
C
NO2
O2N
CN
3t, 74%, 10 h
3p, 77%, 11 h
O
3q, 72%, 12 h
3r, 63%, 13 h
3u, 78%, 10 h
aReaction conditions: Aryl diazonium fluoroborate (0.5 mmol), PhCOCO2H (1 mmol),
Pd(PhCN)2Cl2 (5 mol %), (NH4)2S2O8 (1 equiv.), DMF (3 ml), 90 oC, Ar atm., 10 h.
bIsolated yield.
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Substituted aryl glyoxylic acids also successfully participated in this reaction with aryl
diazonium fluoroborates and the corresponding products were obtained with good to excellent
yields. The results are summarized in Table 3.
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Table 3. Pd catalyzed synthesis of aryl ketones from substituted aryl diazonium
fluoroborates and substituted aryl glyoxylic acid a, b
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O
O
Pd(PhCN)2Cl2
(NH4)2S2O8
F4BN2
OH
R
R
R
R
DMF, 90 oC, Ar
10 h
O
O
O
O
O
H
OMe
3C
Br
H3
C
H3
C
Cl H3
C
4a, 81%, 10 h
O
4c, 88%, 10 h
O
4b, 74%, 10 h
O
4d, 81%, 10 h
O
MeO
OMe
MeO
CH3
H3CH2
C
4h, 89%, 10 h
4g, 81%, 10 h
4f, 80%, 10 h
O
4e, 71%, 10 h
O
O
O
Cl
O
CH3
Cl
OMe
MeO
Cl
CH3
MeO
Br
4k, 80%, 11 h
O
4l, 78%, 11 h
4j, 84%, 10 h
O
4i, 71%, 10 h
O
S
Br
CH3 NC
4p, 88%, 10 h
4m, 72%, 11 h
4n, 77%, 10 h
4o, 66%, 12 h
aReaction conditions : Aryl diazonium fluoroborate (0.5 mmol), PhCOCO2H (1 mmol),
Pd(PhCN)2Cl2 (5 mol %), (NH4)2S2O8 (1 equiv.), DMF (3 mL), 90 oC, Ar atm., 10 h.
bIsolated yield.
A variety of functional groups such as ꢀF, ꢀNO2, ꢀCN, ꢀOMe, ꢀMe, ꢀBr, ꢀCl, ꢀCO2Me, ꢀCF3 on
aryl diazonium fluoroborates and ꢀCN, ꢀOMe, ꢀMe, ꢀBr, ꢀCl, on aryl glyoxylic acid are
compatible for these reactions and the corresponding products were obtained without any
difficulty. A heteroarylꢀaryl ketone (Table 3, 4p) was also obtained by this procedure.
A gram scale reaction was performed successfully by this procedure. This certainly indicates its
potential for industrial applications (Table 4).
Table 4. A gram scale reaction by our procedurea
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aReaction conditions : Aryl diazonium fluoroborate (10 mmol, 2.21 g), PhCOCO2H (20 mmol,
3.0 g), Pd(PhCN)2Cl2 (5 mol %, 182 mg), (NH4)2S2O8 (10 equiv., 2.28 g), DMF (20 mL), 90 C,
o
Ar atm., 10 h.
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8
9
In general, the reactions are clean and high yielding. The procedure is simple and relatively mild.
It is also cost effective using inexpensive aryl amines and employing no ligand. The aryl
diazonium tetrafluoroborates were prepared by a reported procedure using sodium nitrite, sodium
tetrafluoroborate and aryl amines.14 The aryl ketones were obtained pure and were properly
characterized by spectroscopic data. This procedure gives an access to diverse diaryl ketones
with good to excellent yield.
To understand the nature of the reaction pathway (radical/ionic), when a reaction of 4ꢀfluoro
diazonium fluoroborate and phenyl glyoxylic acid was performed in the presence of TEMPO
((2,2,6,6ꢀTetramethylpiperidinꢀ1ꢀyl)oxyl), a radical quencher, the reaction was virtually arrested
(Table 5). The radical quencher (TEMPO) adduct was isolated and identified as compound 5b
(1H, 13C NMR, HRMS, see SI), formed by the interaction of TEMPO and acyl radical.
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Table 5. Reaction with radical quencher, TEMPO
Product
With TEMPO
2 equiv.
5a
5b
48 %
25 %
14 %
32 %
53 %
68 %
4 equiv.
6 equiv.
This observation suggests that the reaction is likely to follow a radical pathway. We also
performed a reaction with phenyl glyoxylic acid in the absence of aryl diazonium fluoroborate
and the dimerization product of acyl radical is obtained (Table 6). (see supporting information).
Table 6. Reaction in the absence of diazonium fluoroboratea
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aReaction conditions : PhCOCO2H (2 mmol), Pd(PhCN)2Cl2 (5 mol %), (NH4)2S2O8 (1 equiv.), DMF (3 mL), 90 oC,
Ar atm., 10 h.
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7
8
9
These two experiments establish that an acyl radical is formed by the decarboxylation of αꢀ
oxocarboxylic acid during the initial stage of the reaction.
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We then carried out an UV spectroscopic analysis of the reaction of 4ꢀfluoro diazonium
fluoroborate with phenyl glyoxylic acid under standardized reaction conditions (Figure 2). This
study shows two absorbance in blue shift region at 381 nm and 328 nm with respect to
absorbance of Pd(PhCN)2Cl2 at 432 nm, corresponding to higher oxidation state of Pd
intermediate.15a
Figure 2. UV spectroscopic study of the reaction at different time interval
To understand the nature of intermediates we performed a series of EPR experiments at different
stages of the reaction (See SI). The EPR (Electron Paramagnetic Resonance) study of the
reaction of 4ꢀfluoro diazonium fluoroborate with phenyl glyoxylic acid under the standardized
reaction conditions indicates the presence of an organoꢀradical (g5 = 2.049) (Figure 3A) and the
hyperfine peaks at g1 = 2.529, g2 = 2.411, g3 = 2.308, g4 = 2.217 (Figure 3A) suggest the
appearance of PdIII intermediate15b (see the Supporting Information). The EPR study of the
reaction with phenyl glyoxylic acid in the absence of diazonium fluoroborate (Figure 3B) shows
an identical spectra corresponding to the organoradical species in the original one (Figure 3A).
This indicates that the acyl radical interacts with the Pd catalyst to form the PdIII intermediate.
This intermediate is considerably stable in the absence of diazonium fluoroborate (See SI).
However, the addition of aryl diazonium tetrafluoroborate demonstrates the gradual
disappearance of the Pd(III) intermediate with time as revealed by EPR study (Figure 3C) .
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0 min
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Magnetic Field (G)
Magnetic Field (G)
180 min
3D
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Magnetic Field (G)
Figure 3. EPR spectroscopic study of the reaction at different conditions
The EPR analysis of the reaction mixture at 180 min indicates the presence of Pd(III) (Figure
3D). Thus it may be concluded that the UV peak at 381nm at 180 , 160, 140 min is due to the
presence of relatively stable Pd(III) intermediate. It is likely that the peak at 328 nm in UV
spectroscopy is due to Pd(IV) complex.
Based on these information a reaction mechanism is proposed as outlined in Scheme 3. Initially
the acyl radical formed by the decarboxylation of glyoxylic acid in the presence of an oxidizing
agent interacts with Pd catalyst to form a Pd(III) complex A which then interacts with aryl
diazonium fluoroborate leading to the intermediate B. As (NH4)2S2O8 is a two electron oxidant15c
it is likely that one electron is used to generate the acyl radical from phenyl glyoxylic acid and
the other one is involved in the second step (A to B) in the transformation from Pd(III) to Pd(IV)
complex during coupling with aryl diazonium fluoroborate.15d,15e Subsequently this intermediate
B readily provides the desired product by reductive elimination process.
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O
II
Pd(PhCN)2Cl2
Ar
Ar1
O
O
oxidant
CO2
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Ar1
Ar1
CO2H
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IV
III
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Ar
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Ar1
O
B
Ar1
O
A
oxidant
ArN2BF4
Scheme 3. Possible reaction pathway
Conclusion
In conclusion, we have developed an efficient and general method for the synthesis of
unsymmetrical diaryl ketones by the decarboxylative coupling of aryl glyoxylic acids and aryl
diazonium tetrafluoroborates in the presence of a Pdꢀcatalyst without any traditional ligand.
Needless to say, the diazonium fluoroborates are derived from anilines. The aryꢀ heteroaryl
ketone was also produced. The significant advantages of this procedure are the use of
inexpensive and readily available anilines as starting materials in place of costly aryl halides and
boronic acids,16 use of no traditional ligand, reaction at relatively low temperature, tolerance to
several functional groups, and high yields of products. A possible reaction pathway has been
suggested. We believe that this procedure will provide a practical alternative to the synthesis of
unsymmetrical diaryl ketones using commercially available and inexpensive anilines.
Experimental Section
General Methods
IR spectra were taken as thin films for liquid compounds and as KBr pellets for solids. NMR
spectra were recorded at 300, 400, 500 MHz for H spectra and at 75, 100, 125 MHz for 13C
spectra in CDCl3 solutions. PhCOCO2H, Pd(PhCN)2Cl2, (NH4)2S2O8 were purchased from
Sigma Aldrich. All diazonium fluoroborate salts and substituted glyoxyllic acids were prepared
by the reported method.14,17
1
Representative experimental procedure for the reaction of p - methoxy diazonium
tetrafluoroborate and phenyl glyoxylic acid for the synthesis of
methoxyphenyl)(phenyl)methanone (Table 2, 3g): A mixture of p ꢀ methoxy diazonium
tetrafluoroborate (0.5 mmol, 114 mg), PhCOCO2H (1 mmol, 150 mg), (NH4)2S2O8 (1 mmol),
and Pd(PhCN)2Cl2 catalyst (5 mol %) in DMSO (3 mL) was stirred at 90 oC (silicon oil bath) for
(4-
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10 hours (TLC) under argon atmosphere and the product was extracted with ethyl acetate. The
extract was washed with sodium bicarbonate solution followed by brine (20 mL). The organic
phase was dried over Na2SO4 and evaporated to leave the crude product, which was purified by
column chromatography over silica gel (hexane/ethyl acetate 98:2) to provide the pure (4ꢀ
1
methoxyphenyl)(phenyl)methanone16a as a gummy liquid (96 mg, 91%). H NMR (300 MHz,
CDCl3): δ = 7.90 ꢀ 7.79 (m, 2H), 7.79 ꢀ 7.69 (m, 2H), 7.65 ꢀ 7.52 (m, 1H), 7.52 ꢀ 7.40 (m, 2H),
7.04 ꢀ 6.90 (m, 2H), 3.89 (s, 3H); C NMR (75 MHz, CDCl3): δ = 195.7, 163.4, 138.4, 132.7,
132.0, 130.2, 129.8, 128.3, 113.7, 55.6.
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Many of these compounds are reported earlier and the unknown compounds were characterized
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properly by their spectroscopic and spectrometric data (IR, H NMR, C NMR, and HRMS).
The known compounds were identified by comparison of their spectroscopic and spectrometric
data with those reported earlier. All these data are provided here.
Benzophenone (Table 2, 3a):18a eluent, hexane/ethyl acetate (98:2), (79 mg, 87%); 1H NMR
13
(300 MHz, CDCl3): δ = 7.90 ꢀ 7.75 (m, 4H), 7.67 ꢀ 7.54 (m, 2H), 7.54 ꢀ 7.42 (m, 4H). C NMR
(75 MHz, CDCl3): δ = 196.9, 137.8, 132.5, 130.1, 128.4.
Phenyl(p-tolyl)methanone (Table 2, 3b):18a eluent, hexane/ethyl acetate (98:2), (86 mg,
88%).1H NMR (300 MHz, CDCl3): δ = 7.75 ꢀ 7.67 (m, 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.54 ꢀ 7.44
13
(m, 1H), 7.39 (dd, J = 8.1, 6.8 Hz, 2H), 7.20 (d, J = 7.9 Hz, 2H), 2.36 (s, 3H); C NMR (75
MHz, CDCl3): δ = 196.6, 143.4, 138.0, 135.0, 132.3, 130.4, 130.0, 129.1, 128.3, 21.8.
Phenyl(o-tolyl)methanone (Table 2, 3c):18a eluent, hexane/ethyl acetate (97:3), (74 mg, 76%).
1H NMR (300 MHz, CDCl3): δ = 8.18 ꢀ 8.10 (m, 2H), 7.76 ꢀ 7.68 (m, 1H), 7.57 (dd, J = 8.4, 7.0
Hz, 2H), 7.34 ꢀ 7.27 (m, 2H), 7.26 (dd, J = 3.3, 1.9 Hz, 1H), 7.22 (t, J = 2.6 Hz, 1H), 2.30 (s,
13
3H); C NMR ( 75 MHz, CDCl3): δ = 185.6, 162.0, 148.7, 135.3, 132.5, 131.7, 130.2, 129.2,
127.3, 127.0, 121.7, 16.3.
Phenyl(m-tolyl)methanone (Table 2, 3d):18a eluent, hexane/ethyl acetate (98:2), (79 mg, 81%).
1H NMR (300 MHz, CDCl3): δ = 7.86 ꢀ 7.76 (m, 2H), 7.64 (s, 1H), 7.58 (qd, J = 5.0, 3.8, 1.4 Hz,
2H), 7.47 (dd, J = 8.1, 6.7 Hz, 2H), 7.42 ꢀ 7.31 (m, 2H), 2.41 (s, 3H); 13C NMR (75 MHz,
CDCl3): δ = 196.9, 138.1, 137.8, 137.6, 133.2, 132.3, 130.5, 130.0, 128.6, 128.3, 128.1, 127.4,
21.4.
(2,6-Dimethylphenyl)(phenyl)methanone (Table 2, 3e):16a eluent, hexane/ethyl acetate (97:3),
(72 mg, 69%). 1H NMR (300 MHz, CDCl3): δ = 8.20 ꢀ 8.10 (m, 2H), 7.84 ꢀ 7.65 (m, 1H), 7.64 ꢀ
13
7.53 (m, 2H), 7.13 (s, 3H), 2.29 (d, J = 0.6 Hz, 6H); C NMR (75 MHz, CDCl3): δ = 185.8,
161.8, 147.5, 135.4, 132.5, 130.2, 129.3, 129.0, 126.8, 16.5.
(4-Ethylphenyl)(phenyl)methanone (Table 2, 3f):7i eluent, hexane/ethyl acetate (98:2), (92 mg,
88%). 1H NMR (300 MHz, CDCl3): δ = 7.83 ꢀ 7.77 (m, 2H), 7.77 ꢀ 7.72 (m, 2H), 7.64 ꢀ 7.53 (m,
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1H), 7.52 ꢀ 7.42 (m, 2H), 7.39 ꢀ 7.27 (m, 2H), 2.74 (q, J = 7.6 Hz, 2H), 1.29 (t, J = 7.6 Hz, 3H);
13C NMR (75 MHz, CDCl3): δ = 196.7, 149.6, 138.1, 135.2, 132.3, 130.5, 130.1, 128.3, 127.9,
29.1, 15.4.
7
(2-Fluorophenyl)(phenyl)methanone (Table 2, 3h): 7i eluent, hexane/ethyl acetate (99:1), (78
mg, 75%). 1H NMR (300 MHz, CDCl3): δ = 7.84 (dt, J = 8.4, 1.3 Hz, 2H), 7.66 ꢀ 7.51 (m, 3H),
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7.51 ꢀ 7.43 (m, 2H), 7.32 ꢀ 7.23 (m, 1H), 7.22 ꢀ 7.11 (m, 1H); C NMR (75 MHz, CDCl3): δ =
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193.6, 160.2 (d, JCꢀF = 250.5 Hz), 137.6, 133.5, 133.2, 133.1, 130.9 (d, JCꢀF = 2.3 Hz), 130.0,
128.6 , 124.4, (d, JCꢀF = 3.8 Hz), 116.4 (d, JCꢀF = 21.8 Hz). 19F NMR (376 MHz, CDCl3) δ = ꢀ
3
2
111.0.
18b
(5-Fluoro-2-methylphenyl)(phenyl)methanone (Table 2, 3i):
eluent, hexane/ethyl acetate
(99:1), (77 mg, 72%). 1H NMR (300 MHz, CDCl3): δ = 7.85 ꢀ 7.75 (m, 2H), 7.67 ꢀ 7.57 (m, 1H),
7.47 (dd, J = 8.2, 6.9 Hz, 2H), 7.31 ꢀ 7.19 (m, 1H), 7.09 (td, J = 8.4, 2.8 Hz, 1H), 7.02 (dd, J =
13
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8.7, 2.8 Hz, 1H), 2.27 (s, 3H); C NMR (75 MHz, CDCl3): δ = 197.3, 160.5 (d, JCꢀF = 243.8
3
3
4
Hz), 140.2 (d, JCꢀF = 6.0 Hz), 137.2, 133.7, 132.6 (d, JCꢀF = 7.5 Hz), 132.3 (d, JCꢀF = 3.8 Hz),
130.2 , 128.8, 117.2 (d, JCꢀF = 21.0 Hz), 115.3 (d, JCꢀF = 22.5 Hz), 19.3. 19F NMR (376 MHz,
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2
CDCl3) δ = ꢀ117.1.
(4-Fluorophenyl)(phenyl)methanone (Table 2, 3j): 18a eluent, hexane/ethyl acetate (98:2), (82
mg, 82%). 1H NMR (300 MHz, CDCl3): δ = 7.92 ꢀ 7.81 (m, 2H), 7.81 ꢀ 7.73 (m, 2H), 7.68 ꢀ 7.55
13
(m, 1H), 7.55 ꢀ 7.44 (m, 2H), 7.21 ꢀ 7.09 (m, 2H); C NMR (75 MHz, CDCl3): δ =195.4, 165.5
1
4
3
(d, JCꢀF = 252.8 Hz), 137.7, 134.0 (d, JCꢀF = 3.0 Hz), 132.8 (d, JCꢀF = 9.0 Hz), 132.6, 130.0,
128.5 , 115.6 (d, 2JCꢀF = 21.8 Hz). 19F NMR (376 MHz, CDCl3) δ = ꢀ105.9.
(3-Chloro-4-methylphenyl)(phenyl)methanone (Table 2, 3k): Yellow solid ; m.p. 78 – 80 oC.
1
eluent, hexane/ethyl acetate (99:1), (93 mg, 81%). H NMR (300 MHz, CDCl3): δ = 7.85 ꢀ 7.71
(m, 3H), 7.70 ꢀ 7.55 (m, 2H), 7.55 ꢀ 7.43 (m, 2H), 7.34 (dd, J = 7.8, 0.9 Hz, 1H), 2.46 (d, J = 0.6
Hz, 3H); 13C NMR (75 MHz, CDCl3): δ = 195.3, 137.5, 136.9, 134.8, 132.7, 130.9, 130.7, 130.1,
128.5, 20.5; IR ( KBr) 2924, 1658, 1599, 1446, 1289, 1261 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M +
H]+ Calcd for C14H12ClO 231.0577; Found 231.0573.
(4-Chloro-3-(trifluoromethyl)phenyl)(phenyl)methanone (Table 2, 3l): Yellow solid ; m.p.
74 ꢀ 76 oC. eluent, hexane/ethyl acetate (98:2), (112 mg, 79%). 1H NMR ( 400 MHz, CDCl3): δ =
7.50ꢀ7.58 (m, 2H), 7.62ꢀ7.66 (m, 2H), 7.77 (d, J ꢀ7.6 Hz, 2H), 7.89ꢀ7.91 (m, 1H), 8.14(s, 1H);
13C NMR (125 MHz, CDCl3): δ = 194.2, 136.8, 136.7, 136.4, 134.1, 133.3, 131.8, 130.0, 129.2,
128.9, 128.8, 122.6 (q, 1JCꢀF = 272.5 Hz). IR ( KBr) 2925, 1652, 1593, 1307, 1262 cmꢀ1; HRMS
(ESIꢀTOF) m/z: [M + H]+ Calcd for C14H8ClF3O 285.0294; Found 285.0288.
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(2,3-Dichlorophenyl)(phenyl)methanone (Table 2, 3m):18d eluent, hexane/ethyl acetate (99:1),
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(85 mg, 68%). H NMR (300 MHz, CDCl3): δ = 7.95 ꢀ 7.72 (m, 2H), 7.63 (dddd, J = 14.7, 7.7,
3.1, 1.6 Hz, 2H), 7.53 ꢀ 7.40 (m, 2H), 7.38 ꢀ 7.21 (m, 2H); 13C NMR (75 MHz, CDCl3): δ =
194.3, 140.9, 136.1, 134.2, 134.1, 132.9, 132.3, 131.8, 130.2, 129.3, 128.9, 127.7, 127.0.
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(4-Bromophenyl)(phenyl)methanone (Table 2, 3n): 7c eluent, hexane/ethyl acetate (98:2), (112
mg, 86%). 1H NMR (300 MHz, CDCl3): δ = 7.82 ꢀ 7.72 (m, 2H), 7.72 ꢀ 7.56 (m, 5H), 7.56 ꢀ 7.43
(m, 2H); 13C NMR (100 MHz, CDCl3): δ = 195.7, 137.3, 136.5, 132.8, 131.8, 131.7, 130.1,
128.6, 127.7.
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4-Benzoylbenzonitrile (Table 2, 3o): 7b eluent, hexane/ethyl acetate (98:2), (77 mg, 75%). H
NMR (300 MHz, CDCl3): δ = 8.19 ꢀ 8.09 (m, 2H), 7.93 ꢀ 7.84 (m, 1H), 7.85 ꢀ 7.75 (m, 2H), 7.69
ꢀ 7.56 (m, 1H), 7.56 ꢀ 7.43 (m, 3H); 13C NMR (75 MHz, CDCl3): δ = 172.3, 133.9, 133.5, 132.3,
130.4, 130.3, 130.2, 129.5, 128.8, 128.6.
1
3-Benzoylbenzonitrile (Table 2, 3p): 18e eluent, hexane/ethyl acetate (98:2), (79 mg, 77%). H
NMR (400 MHz, CDCl3): δ = 8.63 (t, J = 1.9 Hz, 1H), 8.45 (ddd, J = 8.3, 2.3, 1.2 Hz, 1H), 8.15
13
(dt, J = 7.7, 1.4 Hz, 1H), 7.90 ꢀ 7.76 (m, 2H), 7.76 ꢀ 7.62 (m, 2H), 7.54 (t, J = 7.7 Hz, 2H); C
NMR (75 MHz, CDCl3): δ = 194.3, 148.3, 144.3, 139.2, 136.4, 135.6, 133.5, 130.2, 129.8,
128.9, 126.9, 124.9.
7b
(4-Nitrophenyl)(phenyl)methanone (Table 2, 3q): eluent, hexane/ethyl acetate (98:2), (81
mg, 72%). 1H NMR (300 MHz, CDCl3): δ= 8.40 ꢀ 8.26 (m, 2H), 8.01 ꢀ 7.87 (m, 2H), 7.87 ꢀ 7.75
(m, 2H), 7.74 ꢀ 7.59 (m, 1H), 7.59 ꢀ 7.47 (m, 2H); 13C NMR (75 MHz, CDCl3): δ = 194.9, 150.0,
143.0, 136.4, 133.6, 130.8, 130.2, 128.8, 123.7.
18f
(2-Nitrophenyl)(phenyl)methanone (Table 2, 3r):
eluent, hexane/ethyl acetate (98:2), (71
mg, 63%). 1H NMR (300 MHz, CDCl3): δ = 8.24 (dd, J = 8.2, 1.3 Hz, 1H), 7.84 ꢀ 7.72 (m, 3H),
7.72 ꢀ 7.64 (m, 1H), 7.59 (tt, J = 7.9, 1.4 Hz, 1H), 7.52 ꢀ 7.40 (m, 3H); 13C NMR (75 MHz,
CDCl3): δ = 193.6, 136.0, 134.3, 134.0, 133.5, 130.7, 129.4, 129.0, 128.9, 124.9, 124.6.
Methyl 4-benzoylbenzoate (Table 2, 3s): 7l eluent, hexane/ethyl acetate (98:2), (85 mg, 71%).
1H NMR (300 MHz, CDCl3): δ = 8.08 ꢀ 7.99 (m,3 H), 7.99 ꢀ 7.92 (m, 1H), 7.59 ꢀ 7.48 (m, 1H),
13
7.46 ꢀ 7.34 (m, 4H), 3.90 (d, J = 2.2 Hz, 3H); C NMR (75 MHz, CDCl3): δ = 196.2, 166.5,
141.5, 137.1, 133.4, 133.1, 133.3, 129.9, 129.6, 128.6, 52.6.
Phenyl(2-(trifluoromethyl)phenyl)methanone (Table 2, 3t):18f eluent, hexane/ethyl acetate
(99:1), (92 mg, 74%). 1H NMR (300 MHz, CDCl3): δ = 7.78 (dt, J = 7.1, 1.4 Hz, 3H), 7.66 ꢀ 7.56
(m, 3H), 7.50 ꢀ 7.35 (m, 3H); 13C NMR (125 MHz, CDCl3): δ = 195.6, 138.6, 136.7, 133.9,
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131.5, 130.3, 129.9, 128.7,128.4, 128.3, 126.9, 123.8 (q, JCꢀF = 272.5 Hz). 19F NMR (376 MHz,
CDCl3) δ = ꢀ58.0.
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Naphthalen-2-yl(phenyl)methanone (Table 2, 3u):18a eluent, hexane/ethyl acetate (99:1), (90
1
mg, 78%). H NMR (300 MHz, CDCl3): δ = 8.28 (d, J = 1.2 Hz, 1H), 7.99 ꢀ 7.90 (m, 3H), 7.86
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(ddd, J = 8.1, 4.6, 2.1 Hz, 2H), 7.67 ꢀ 7.58 (m, 2H), 7.58 ꢀ 7.51 (m, 2H), 7.51 ꢀ 7.44 (m, 2H); C
NMR (75 MHz, CDCl3): δ = 196.9, 138.1, 135.4, 135.0, 132.5, 132.4, 132.0, 130.2, 129.6, 128.5,
128.0, 126.9, 126.0, 121.3, 118.7.
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(4-Chlorophenyl)(p-tolyl)methanone (Table 3, 4b):18c eluent, hexane/ethyl acetate (98:2), (85
mg, 74%). 1H NMR (300 MHz, CDCl3): δ = 7.80 ꢀ 7.61 (m, 4H), 7.53 ꢀ 7.39 (m, 2H), 7.39 ꢀ 7.21
(m, 2H), 2.44 (s, 3H); 13C NMR (75 MHz, CDCl3): δ = 195.4, 143.7, 138.7, 136.4, 134.7, 131.5,
130.3, 129.2, 128.7, 21.8.
(4-Methoxyphenyl)(p-tolyl)methanone (Table 3, 4c):18c eluent, hexane/ethyl acetate (98:2), (99
mg, 88%).1H NMR (300 MHz, CDCl3): δ = 7.97 ꢀ 7.74 (m, 2H), 7.74 ꢀ 7.62 (m, 2H), 7.37 ꢀ 7.21
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(m, 2H), 7.03 ꢀ 6.88 (m, 2H), 3.88 (s, 3H), 2.43 (s, 3H); C NMR (75 MHz, CDCl3): δ = 195.5,
163.2, 142.7, 135.6, 132.5, 130.6, 130.1, 129.0, 113.6, 55.6, 21.7.
(4-Bromophenyl)(p-tolyl)methanone (Table 3, 4d):18g eluent, hexane/ethyl acetate (99:1), (111
mg, 81%). 1H NMR (300 MHz, CDCl3): δ = 7.69 (d, J = 8.0 Hz, 2H), 7.66 ꢀ 7.57 (m, 4H), 7.30
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(s, 1H), 7.27 (d, J = 4.4 Hz, 1H), 2.45 (s, 3H); C NMR (75 MHz, CDCl3): δ = 195.5, 143.7,
136.8, 134.6, 131.7, 131.6, 130.3, 129.2, 127.3, 21.8.
Bis(4-methoxyphenyl)methanone (Table 3, 4h):18a eluent, hexane/ethyl acetate (97:3), (107
mg, 89%). 1H NMR (300 MHz, CDCl3): δ = 8.21 ꢀ 8.00 (m, 4H), 7.10 ꢀ6.87 (m, 4H), 3.89 (d, J
= 5.6 Hz, 6H); 13C NMR (75 MHz, CDCl3): δ = 171.5, 133.0, 132.5, 114.3, 113.9, 55.6.
(4-Chlorophenyl)(4-methoxyphenyl)methanone (Table 3, 4i):18h eluent, hexane/ethyl acetate
(98:2), (87 mg, 71%).1H NMR (300 MHz, CDCl3): δ = 8.14 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.5
Hz, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.45 (d, J = 8.3 Hz, 1H), 7.38 (d, J = 8.6 Hz, 1H), 7.15 (d, J =
13
8.4 Hz, 1H), 7.05 ꢀ 6.93 (m, 2H), 3.90 (s, 3H); C NMR (75 MHz, CDCl3): δ = 163.5, 136.7,
132.6, 132.5, 131.7, 131.3, 131.2, 123.0, 129.6, 128.7, 123.3, 114.1, 113.8, 55.7.
Phenyl(thiophen-2-yl)methanone (Table 3, 4p):16a eluent, hexane/ethyl acetate (98:2), (82 mg,
1
88%). H NMR (300 MHz, CDCl3): δ = 7.94 ꢀ 7.82 (m, 2H), 7.73 (dd, J = 5.0, 1.1 Hz, 1H),
7.65 (dd, J = 3.8, 1.1 Hz, 1H), 7.63 ꢀ 7.56 (m, 1H), 7.50 (dd, J = 8.2, 6.6 Hz, 2H), 7.17 (dd, J =
4.9, 3.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ = 188.4, 143.8, 138.3, 135.0, 134.4, 132.4,
129.3, 128.6, 128.1.
2,2,6,6-Tetramethylpiperidin-1-yl benzoate (Table 5, 5b):18i eluent, hexane/ethyl acetate
(98:2), (88 mg, 68%, based on 0.5 mmol scale). 1H NMR (300 MHz, CDCl3) δ = 8.40 (d, J = 7.4
Hz, 2H), 7.83 (d, J = 31.9 Hz, 3H), 2.28 – 1.71 (m, 7H), 1.58 (d, J = 8.5 Hz, 6H), 1.43 (d, J = 8.7
Hz, 5H). 13C NMR (75 MHz, DMSOꢀd6) δ = 163.1, 132.5, 128.3, 127.6, 127.1, 57.6, 37.3, 30.1,
19.2, 15.3.
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Supporting Information
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The H, and C NMR spectra of all products, 19F spectra (3h,3i,3j and 3t), HRMS (5b and 6a)
and EPR study of the reaction pathway. This material is available free of charge via the Internet
at http:// pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: ocbcr@iacs.res.in.
Notes
Any additional relevant notes should be placed here.
Acknowledgements
We are pleased to acknowledge the financial support from Indian National Science Academy, New Delhi
for the award of INSA Senior Scientist position to B.C.R. S. P. thanks CSIR for his fellowship. We thank
Professor Tapan K. Paine of department of Inorganic Chemistry of our Institute for helpful discussions.
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