Revisiting 1-chloro-1,2-benziodoxol-3-one: Efficient: ortho -chlorination of aryls under aqueous conditions

Article abstract of DOI:10.1039/c8nj00530c

The application of 1-chloro-1,2-benziodoxol-3-one as a powerful chlorinating agent as well as oxidant for aniline derivatives is explored. The amide directing group assisted radical mediated ortho-selective chlorination proceeds in the absence of a radical initiator. Various electronically differentiated anilides and sulfonamides are tolerated under aqueous conditions.

Full text of DOI:10.1039/c8nj00530c

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The role of atropisomers on the photo-reactivity and fatigue of
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Revisit of 1-Chloro-1,2-benziodoxol-3-one: Efficient ortho-
Chlorination of aryls under aqueous conditions.
Received 00th January 20xx,
Accepted 00th January 20xx
Botla Vinayak, Pardhi Vishal Ravindrakumar, Daggupati V. Ramana and Malapaka
Chandrasekharam*
DOI: 10.1039/x0xx00000x
The application of 1-chloro-1,2-benziodoxol-3-one as a powerful chlorinating agent as well as oxidant on aniline
derivatives is explored. The amide directing group assisted radical mediated ortho-selective chlorination proceeds in the
absence of radical initiator. Various electronically differentiated anilides and sulfonamides are tolerated under aqueous
conditions.
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functional materials and cores of dyes and pigments, the efficient
and practical chlorination of aniline derivatives deserve thorough
investigations.5 However the related reports in the literature are
relatively scarce. The reports published by Shi and Bedford groups
Introduction
are associated with limitations such as employing industrially
unfavorable solvents or precious metal catalysts.6 An elegant and
ortho-selective chlorination of anilines employing 1,3-dichloro-5,5-
dimethylhydantoin (DCDMH) as halogen source has been achieved
by Yeung and co-workers.7 In a recent publication, Zhou and Xu
reported nucleophilic ortho-halogenation of the aniline substrates
that are otherwise prone to electrophilic halogenations, following
Apart from being an important functional group by itself, the ease
of functionalizability of chlorine, generated tremendous interest on
chlorination of aryls in recent times. Akin to fluorination and unlike
bromination and iodination, chlorination often contributes to the
improvement of biological activities in agrochemical as well as drug
discoveries. However the potential application of aryl chlorides in
the cross coupling arena is not so fully explored on par with the
corresponding bromides and iodides, essentially due to their
relative inaccessibility combined with less reactivity. Thus a large
space is left unexplored in this area and further investigations of
aryl chlorination are most sought after.
umpolung strategy via TFAA assisted directing thionium ion.8
A
recent report also describes the aryl chlorination occurred
presumably via fluoride-chloride exchange along with fluorination
on limited amides employing selectfluor.9 Surprisingly, the age-old
reagent, 1-chloro-1,2-benziodoxol-3-one is yet to gain wide
application in chlorination reactions,10a, b the only report on metal
free aryl chlorination with the reagent involves industrially
unacceptable DMF solvent and follows an ionic mechanism.10c Our
continued efforts towards C-H functionalizations (C-C, C-O and C-N)
of aryls prompted us to investigate ortho-chlorination of aniline
derivatives with amido directing group.11 Further in the context of
traceless-, easily removable-, and transient-directing groups gaining
importance, the amide directing group after C-H functionalization,
is known to be easily removable or transformed to other useful
functional groups via the deprotection-diazotization protocol.12 Our
present work demonstrates the application of 1-chloro-1, 2-
benziodoxol-3-one, an easily accessible and recyclable reagent as an
oxidant as well as chlorinating agent for the direct ortho-selective
chlorination of anilides and sulfonamides under aqueous conditions
as a green approach (Scheme 1).
In general, aromatic C-H chlorination methodologies could be
categorized as follows. (1). Electrophilic aromatic substitution,
being classical and widely employed but the reagents could be too
reactive and hence unselective; unreactive in the absence of strong
electron-donating groups on the aryl system,1 (2). Employing Cl+
source via hydrogen-metal exchange reaction,2 though regio-
selective, necessitates strong base and a directing group. (3).
Transition metal catalyzed C-H activation with assured
regioselectivity and limited substrate scope.3 However exploitation
of the innate reactivity is a classical and widely employed method
to prepare aromatic chlorides. While several chlorination reagents
for the direct aromatic chlorination are available in literature, each
one under the reported reaction conditions suffer from certain
limitations.1 Baran’s invention, Palau’chlor, a practical guanidine
based chlorination reagent, is highly efficient towards this effort.4
Scheme 1. Ortho-chlorination of anilides and sulfonamides.
Owing to their presence in pharmaceutical building blocks, novel

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1.0 equiv. of 1b and 1.2 equiv. of 1-chloro-1, 2-benziodoxol-3-one in
5 mL of solvent at 90 °C for 16 h. With the optimized conditions in
hand, the substrate scope of the reaction was investigated on a
variety of electronically differentiated aryls (Scheme 2).
Results and discussion
Scheme 2. Ortho-chlorination of anilides and sulfonamides.a
We began our study with N-(p-tolyl)benzamide (1b) as a model
substrate. Stirring a solution of (1b), 1-chloro-1, 2-benziodoxol-3-
one in a 1, 2 DCE solution at room temperature resulted in the
recovery of starting material (Table 1, entry 1). When the
temperature was increased to 60 °C, the desired product 2b was
formed in low yields 38% (Table 1, entry 2), whereas the reaction
under reflux at 90 °C for 16hrs proceeded with improved yield of 60
%. (Table 1, entry 2) Prolonged reaction time did not improve the
yields further. In order to set optimum conditions we screened the
reaction with various solvents i.e., toluene, 1,4-dioxane, ACN, AcOH
and H2O and obtained 51%, 14%, 43%, 35% and <15% yields of the
chlorinated product respectively (Table 1, entries 4-8). DMF solvent
was found to be reasonable furnishing 63% yield of the chlorinated
product. (Table 1, entry 9) Protic solvents i.e., MeOH, EtOH and Iso-
Propanol too worked well for the reaction and produced 65%, 63%,
60% yields respectively (Table 1, entries 10-12). Interestingly the
reaction proceeds well in aqueous alcohol conditions too (Table 1,
entries 12-20).
Table 1. Optimization of the reaction conditions.a
Cl
O
O
Solvent
I
NH
Cl
NH
O
O
2b
1b
S.No
Solvent
Temp
(°C)
Time
(h)
24
24
16
16
16
16
16
16
16
16
10
16
16
16
16
16
16
16
Yield
(%)b
00
38
60
51
14
43
35
<15%
63
65
63
60
71
70
66
67
1
2
3
4
5
6
7
8
9
10
11
12
14
15
16
18
19
20
1,2 DCE
1,2 DCE
1,2 DCE
Toluene
1,4-Dioxane
CAN
AcOH
H2O
DMF
MeOH
EtOH
Rt
60
reflux
83
83
reflux
83
83
aThe reaction was performed with 1b (1.0 equiv), chlorinating reagent (1.2 equiv) in Aq
EtoH (1:4) (3 mL) the reaction mixture was refluxed for 16 h in an open air atmosphere.
All are isolated yields.
83
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
Reflux
Iso-Propanol
Aq. MeOH (1:4)
Aq. EtOH (1:4)
Aq. Iso-Propanol (1:4)
Aq. EtOH (1:3)
The benzanilide furnished moderate yield (63%) of the ortho-
chlorinated product under standard reaction conditions (Scheme 2,
2a). Good yields (70%, 74%) were often obtained when electron-
donating moieties i.e., methyl, ethyl were present on the para-
position of the aniline ring (Scheme 2, 2b, 2d). However with fluoro,
chloro, bromo, iodo, and trifluoromethyl groups present on the
para position, the reaction proceeded with moderate yields
(Scheme 2, 2e–2i). The steric crowding in the substrates, 1c and 1j
inhibited ortho-chlorination, and led to the para- chlorination
products instead with 51%, 55% of yields respectively (Scheme 2,
2c, 2j). In addition, substrates with a strong electron withdrawing R1
group at the para position i.e., CN or Nitro severely retarded the
chlorination of the aromatic ring resulting in the formation of no
desired product even after prolonged reaction times (Scheme 2, 2k,
2l).
Aq. EtOH (1:2)
Aq. EtOH (1:1)
65
61
aThe reaction was performed with 1b (1.0 equiv), chlorinating reagent (1.2 equiv) in Aq
EtoH (3 mL) the reaction mixture was refluxed for 16 h in an open air atmosphere
unless otherwise noted. bIsolated yields.
However considering the green principles, aq. ethanol (1:4) was
selected as the optimized solvent condition to explore the substrate
scope for the ortho-chlorination of anilines. The complete
optimized conditions require stirring and refluxing of a mixture of
2 | J. Name., 2012, 00, 1-3
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Substrates with different carboxamides (aryl, heteroaryl, alkyl, and Further the fact that anisole and N-benzyl indole are also unreactive
vinyl) showed similar reactivity, and the yields were moderate to towards chlorination, rules out the electrophilic substitution
good (Scheme 2, 2m-2u). Substrates with cycloalkyl/alkyl groups at (Scheme 3). Diminished yields of the chlorination product 2b
the para position of the aniline/carboxamide ring proceeded with obtained when the reaction was conducted in the presence of free
moderate to good yields (64%, 65%) of the corresponding radical scavengers TEMPO (2.0 equiv.) and 1, 1 diphenylethylene
chlorination products (Scheme
2 entry 2m, 2n). 4-Fluoro (2.0 equiv.) (Scheme 4, eq. 1 and 2), demonstrate that the reaction
substitution on the carboxamide ring did not affect the o- may have proceeded through a radical mechanism. Furthermore,
chlorination yields under standard reaction conditions (Scheme 2 non-reactivity with N-methyl-N- phenylbenzamide towards
2o). The strong electron-withdrawing groups such as 4- chlorination reflected the key role of N-H bond on the amide group
trifluoromethyl or 4-nitro benzamides also showed reasonably in the reaction pathway (Scheme 4 eq. 3). Although the reaction
good reactivity towards this chlorination reaction (Scheme 2, 2p, mechanism is not clear yet, from the above observations and
2q). Further, a heteroaryl substrate also underwent smooth ortho- literature precedence, a plausible mechanism involving a radical
chlorination reaction in good yield 62% (Scheme 2, 2r). The pathway has been proposed (Scheme 5).
chlorination reaction with alkyl and vinyl carboxamides also
proceeded smoothly under the standard reaction conditions with
Scheme 5. Proposed Mechanism
.
good yield (Scheme 2, 2s-2u). The sulfonamides, (Scheme 2, 2v-2x)
subjected to ortho-chlorination under the optimized reaction
conditions furnished the corresponding products in good yields (61-
68%). The above studies reveal that the reagent is highly selective
for the ortho-chlorination of aniline derivatives leaving the
carboxamide ring unaffected irrespective of electronically different
substitutions on either of the aryl rings. Hence it clearly indicates
that 1-Chloro-1,2-benziodoxol-3-one is relatively mild and hence a
selective chlorinating agent.
R
NH
I
Cl
OH
I
O
O
H
O
Cl
I
I
O
O
Scheme 3. Substrate resistant to Ortho-chlorination.
O
O
R
R
R
N
N
N
A
Cl
Cl
R
R
NH
NH
Cl
Aniline, N,N-dimethyl aniline, N-benzyl aniline and N-Boc aniline
were found to be resistant to chlorination under the standard
conditions.
Cl
The above observations in accordance with our previous
reports,11e,g anilidyl radicals9 as well as a similar amide-assisted
mechanism. Therefore it is presumed that an amide assisted radical
mechanism might be involved in our transformation. Initially, 1-
chloro-1, 2-benziodoxol-3-one, as an oxidant generates the anilide
Scheme 4. Mechanistic Investigations
.
13
radical, chlorine radical and iodo benzoic acid. Then the reaction
appears to have proceeded via the recombination of chlorine
radical with the anilidyl radical preferably at the ortho position,
producing selectively ortho-chloro aniline derivative. The reaction
occurs in the absence of metal/catalyst or a radical initiator in
aqueous medium.
O
O
standerd reaction
conditions
......eq. 1
NH
NH
TEMPO (2.0 eq.)
Cl
1b
1b
2b
>10 %
O
O
standerd reaction
conditions
......eq. 2
NH
NH
Conclusions
1,1 DPE (2.0 eq.)
Cl
2b 0 %
In conclusion, for the first time we have demonstrated an
ortho-selective directing group assisted chlorination of aryls
with easily accessible reagent 1-Chloro-1,2-benziodoxol-3-one.
The hypervalent iodine based reagent serves as oxidant as well
as chlorinating agent and is known for easy preparation, post
reaction purification and recyclability. The amide directing
group is easily removable and could be transformed further to
O
O
standerd reaction
conditions
......eq. 3
N
N
Cl
0 %
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other functional groups via deprotection-diazotisation N-(2-chloro-4-methylphenyl)benzamide (2b):9 The title compound
sequence. This new radical mediated C-H functionalization
reaction tolerates broad and electronically differentiated
substrates under the aqueous reaction conditions. Further a
radical pathway assisted by amide N-H has been proposed in
the absence of a radical initiator. Investigations on new
applications of this conventional reagent are underway
applying green principles.
was prepared according to the general procedure 100 mg (0.47
o
mmol) of 1b, 81 mg of 2b (70% yield). White Solid, mp: 139-140 C.
1H NMR (500 MHz, CDCl3) δ = 8.41 (d, J = 8.39 Hz, 1H), 8.36 (Br s,
1H), 7.94-7.89 (m, 2H), 7.60-7.55 (m, 1H), 7.54-7.49 (m, 2H), 7.25-
7.22 (m, 1H), 7.16-7.11 (m, 1H), 2.33 (s, 1H). 13C NMR (100 MHz,
CDCl3) δ = 165.22, 134.92, 132.10, 129.43, 128.94, 128.51, 127.09,
122.92, 121.46, 20.73. ESI-MS: m/z 246 (M+H) +.
N-(4-chloro-2-methylphenyl)benzamide (2c): 15 The title compound
was prepared according to the general procedure 100 mg (0.47
mmol) of 1c, 59 mg of 2c (51% yield). White Solid, mp: 173-175 °C.
1H NMR (400 MHz, CDCl3) δ = 7.92-7.85 (m, 3H), 7.64 (Br s, 1H),
7.60-7.56 (m, 1H), 7.53-7.48 (m, 2H), 7.25-7.20 (m, 2H), 2.31 (s, 3H).
(100 MHz, CDCl3) δ = 165.80, 134.60, 134.36, 132.07, 131.49,
130.36, 128.90, 127.10, 126.84, 124.63, 17.77. ESI-MS: m/z 246
(M+H) +.
Experimental
General
All commercially available chemicals were used as received.
Thin-layer chromatography plates were visualized by exposure
to UV or Iodine, and/or by immersion in an acidic staining
solution of phosphomolybdic acid followed by heating on a hot
1
plate. H NMR spectra were obtained with 300, 400 and 500
MHz spectrometers, 13C NMR spectra were obtained with 100
and 125 MHz spectrometers in CDCl3 at 298
K with
N-(2-chloro-4-ethylphenyl)benzamide
(2d):
The
title
tetramethylsilane and CDCl3 as the internal standard. Chemical
shifts (δ) are reported in ppm relative to the residual solvent
signal (δ = 7.26 ppm for 1H NMR and δ = 77.0 ppm for 13C
NMR). Data for 1H NMR are reported as follows: chemical shift
(multiplicity, coupling constant, number of hydrogen atoms).
Multiplicity is abbreviated as follows: s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet). Mass spectra were carried
out with a Quattro LC triple-quadrupole mass spectrometer
(Micromass, Manchester, UK). High-resolution mass spectra
were determined with a Quadrupole time-of-flight (Q-TOF)
mass spectrometer (QSTARXL, Applied Biosystems/MDS Sciex,
Foster city, USA).
compound was prepared according to the general procedure
100 mg (0.44 mmol) of 1d, 85 mg of 2d (74% yield). White
Solid, mp: 122-124 °C. 1H NMR (400 MHz, CDCl3) δ =8.43 (d, J =
8.43 Hz, 1H), 8.37 (Br s, 1H), 7.94-7.89 (m, 2H), 7.59-7.55 (m,
1H), 7.53-7.49 (m, 2H), 7.25-7.23 (m, 1H), 7.18-7.13 (m, 1H),
2.63 (q, J = 7.70 Hz, 7.58Hz, 2H), 1.24 (t, J = 7.58 Hz, 3H).13C
NMR (100 MHz, CDCl3) δ = 165.12, 141.24, 134.64, 132.00,
128.82, 128.12, 127.00, 122.99, 121.54, 28.06, 15.34. ESI-MS:
m/z 260 (M+H) +. ESI-HRMS: calcd for C15H15ONCl = 260.08367,
Found 260.08286.
N-(2-chloro-4-fluorophenyl)benzamide (2e): 16 The title compound
was prepared according to the general procedure 100 mg (0.46
mmol) of 1e, 79 mg of 2e (68% yield). White Solid, mp: 108-110 °C.
1H NMR (400 MHz, CDCl3) δ = 8.56-8.47 (m, 1H), 8.31 (Br s, 1H),
7.93-7.88 (m, 2H), 7.62-7.56 (m, 1H), 7.55-7.49 (m, 2H), 7.21-7.15
(m, 1H), 7.10-7.02 (m, 1H).13C NMR (100 MHz, CDCl3) δ = 165.30,
159.74, 157.28, 134.39, 132.30, 131.20, 128.99, 127.10, 123.85
General Procedure for the synthesis ortho-chlorination of anilides
and sulphonamides:
A round bottom flask was charged with anilide (0.5 mmol),
1-Chloro-1,2-benziodoxol-3-one (1.2 equiv, 0.6 mmol), aq. EtOH
(1:4) (3.0 mL) Then, the mixture was refluxed in an oil bath at open 122.87, 116.24, 114.69. ESI-MS: m/z 250 (M+H) +.
air for about 16 h. The progress of the reaction was monitored by
9
TLC. The reaction mixture was cooled to ambient temperature, the
crude compound obtained was washed with a saturated aqueous
solution of NaHCO3 to remove the unwanted 2-iodobenzoic acid
formed, and then extracted with ethyl acetate, and concentrated in
vacuo. The resulting residue was purified by silica gel column
chromatography (hexane/ethyl acetate) to afford the 51– 79%
yield.
N-(2-chlorophenyl)benzamide (2a):14 The title compound was
prepared according to the general procedure 100 mg (0.5 mmol) of
1a, 73 mg of 2a (63% yield). White Solid, mp: 100-102 °C. 1H NMR
(500 MHz, CDCl3) δ = 8.60-8.55 (m, 1H), 8.45 (Br s, 1H), 7.94-7.90
(m, 2H), 7.61-7.56 (m, 1H), 7.54-7.50 (m, 2H), 7.44-7.40 (m, 1H),
7.36-7.32 (m, 1H), 7.11-7.07 (m, 1H). 13C NMR (100 MHz, CDCl3) δ =
164.28, 138.27, 133.82, 131.19, 127.94, 126.89, 126.08, 123.59,
122.01, 120.49, 113.05. ESI-MS: m/z 232 (M+H) +.
N-(2,4-dichlorophenyl)benzamide (2f): The title compound was
prepared according to the general procedure 100 mg (0.43 mmol)
of 1f, 76 mg of 2f (66% yield). White Solid, mp: 119-121 °C. 1H NMR
(400 MHz, CDCl3) δ = 8.54 (d, J = 8.80 Hz, 1H), 8.39 (Br s, 1H), 7.93-
7.88 (m, 2H), 7.62-7.56 (m, 1H), 7.55-7.49 (m, 2H), 7.44-7.41 (m,
1H), 7.33-7.28 (m, 1H). 13C NMR (100 MHz, CDCl3) δ = 164.16,
133.22, 132.47, 131.33, 128.18, 127.95, 127.70, 126.98, 126.05,
122.55, 121.22. ESI-MS: m/z 266 (M+H) +.
N-(4-bromo-2-chlorophenyl)benzamide (2g):9 The title
compound was prepared according to the general procedure
100 mg (0.36 mmol) of 1g, 70 mg of 2g (62% yield). White
Solid, mp: 133-135 °C. 1H NMR (400 MHz, CDCl3) δ = 8.49 (d, J =
8.80 Hz, 1H), 8.39 (s, 1H), 7.92-7.89 (m, 2H), 7.61-7.57 (m, 2H),
7.61-7.57 (m, 2H), 7.54-7.50 (m, 2H), 7.47-7.43 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ = 164.18, 133.22, 132.94, 131.38,
4 | J. Name., 2012, 00, 1-3
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N-(2-chlorophenyl)-4-fluorobenzamide (2o):18 The title compound
was prepared according to the general procedure 100 mg (0.46
mmol) of 1o, 71 mg of 2o (61% yield). White Solid, mp: 101-103 °C.
Yield:. 1H NMR (500 MHz, CDCl3) δ = 8.56-8.49 (m, 1H), 8.37 (Br s,
1H), 7.99-7.88 (m, 2H), 7.45-7.40 (m, 1H), 7.37-7.30 (m, 1H), 7.23-
7.15 (m, 2H), 7.13-7.05 (m, 1H). 13C NMR (100 MHz, CDCl3) δ =
166.42, 164.23, 134.71, 130.80, 129.58, 129.08, 127.95, 124.92,
123.20, 121.84, 116.20, 115.98. ESI-MS: m/z 250 (M+H) +.
130.45, 129.94, 127.98, 126.06, 122.68, 121.48, 115.36. ESI-
HRMS: calcd for C13H10ONBrCl = 309.96288, Found 309.96191.
N-(2-chloro-4-iodophenyl)benzamide (2h):17 The title compound
was prepared according to the general procedure 100 mg (0.31
mmol) of 1h, 65 mg of 2h (59% yield). White Solid, mp: 158-160 °C.
1H NMR (500 MHz, CDCl3) δ = 8.40 (Br s, 1H), 8.37 (d, J = 8.85 Hz,
1H), 7.93-7.89 (m, 2H), 7.76-7.73 (m, 1H), 7.66-7.62 (m, 1H), 7.62-
7.58 (m, 1H), 7.55-7.51 (m, 2H). 13C NMR (100 MHz, CDCl3) δ =
164.16, 136.03, 135.87, 133.61, 133.25, 131.37, 127.98, 126.04,
122.60, 121.70, 85.62. ESI-MS: m/z 358 (M+H) +.
N-(2-chloro-4-methylphenyl)-4-(trifluoromethyl)benzamide (2p):
The title compound was prepared according to the general
procedure 100 mg (0.35 mmol) of 1p, 77 mg of 2p (69% yield).
White Solid, mp: 144-146 °C. 1H NMR (400 MHz, CDCl3) δ = 8.41-
8.30 (m, 2H), 8.02 (d, J = 8.06 Hz, 2H), 7.78 (d, J = 8.19 Hz, 2H), 7.25
(s, 1H), 7.15 (d, J = 9.17 Hz, 2H), 2.34 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ = 163.84, 137.90, 135.47, 131.64, 129.39, 128.50, 127.51,
125.93, 123.12, 121.59, 20.67. ESI-MS: m/z 314 (M+H) +.
N-(2-chloro-4-(trifluoromethyl)phenyl)benzamide (2i): The title
compound was prepared according to the general procedure 100
mg (0.37 mmol) of 1a, 69 mg of 2i (61% yield). White Solid, mp:
1
206-208 °C. H NMR (400 MHz, CDCl3) δ = 8.77 (d, J = 8.68 Hz, 1H),
8.58 (Br s, 1H), 7.96-7.90 (m, 2H), 7.73-7.68 (m, 1H), 7.65-7.58 (m,
2H), 7.57-7.51 (m, 2H). 13C NMR (100 MHz, CDCl3) δ = 164.28,
133.73, 133.61, 131.19, 127.94, 126.89, 126.08, 123.74, 122.01,
120.49, 112.98. ESI-MS: m/z 300 (M+H) +.
N-(2-chloro-4-methylphenyl)-4-nitrobenzamide (2q): The title
compound was prepared according to the general procedure
100 mg (0.39 mmol) of 1q, 76 mg of 2q (67% yield). White
1
Solid, mp: 150-152 °C. H NMR (500 MHz, CDCl3) δ = 8.41-8.31
N-(5-chloro-[1,1'-biphenyl]-2-yl)-4-methylbenzamide (2j):16 The
title compound was prepared according to the general procedure
100 mg (0.36 mmol) of 1j, 62 mg of 2j (55% yield). White Solid, mp:
140-142 °C. 1H NMR (500 MHz, CDCl3) δ = 8.52 (t, J = 7.1 Hz, 1H),
(m, 4H), 8.07 (d, J = 8.85 Hz, 2H), 7. 16 (d, J = 8.24 Hz, 1H), 2.35
(s, 3H).13C NMR (100 MHz, CDCl3) δ = 163.14, 149.89, 140.15,
135.91, 131.45, 129.52, 128.61, 128.31, 124.14, 123.32,
121.73, 20.77. ESI-MS: m/z 289 (M-H) +. ESI-HRMS: calcd for
7.93 (Br s, 1H), 7.54 – 7.50 (m, 2H), 7.48 – 7.45 (m, 3H), 7.43 – 7.40 C14H12O3N2Cl = 291.0536, Found 291.0539.
(m, 2H), 7.39 (dd, J = 8.8, 2.5 Hz, 1H), 7.29 – 7.27 (m, 1H), 7.18 (d, J
= 7.9 Hz, 2H), 2.37 (s, 3H), 13C NMR (100 MHz, CDCl3) δ = 164.93,
142.52, 136.83, 133.70, 131.63, 129.72, 129.41, 129.21, 129.16,
128.68, 128.45, 126.82, 122.28, 21.46. ESI-MS: m/z 308 (M+H) +.
N-(2-chloro-4-cyclohexylphenyl)picolinamide (2r): The title
compound was prepared according to the general procedure
100 mg (0.35 mmol) of 1r, 70 mg of 2r (62% yield).. White
1
Solid, mp: 89-91 °C. H NMR (400 MHz, CDCl3) δ = 10.61 (Br s,
1H), 8.70-8.63 (m, 1H), 8.54–8.50 (m, 1H), 8.32-8.26 (m, 1H),
7.92–7.88 (m, 1H), 7.51–7.47 (m, 1H), 7.26 (m, 1H), 7.20-7.13
(m, 1H), 2.52–2.44 (m, 1H), 1.90–1.82 (m, 4H), 1.79–1.65 (m,
2H), 1.40 (m, 4H), 13C NMR (100 MHz, CDCl3) δ = 162.07,
149.86, 148.29, 145.09, 137.61, 132.34, 127.41, 126.54,
126.18, 123.32, 122.41, 121.11, 43.88, 34.37, 26.79, 26.07. ESI-
MS: m/z 315 (M+H) +. ESI-HRMS: calcd for C18H20ON2Cl =
315.1264, Found 315.1271.
N-(2-chloro-4-cyclohexylphenyl)-4-methylbenzamide
(2m):
The title compound was prepared according to the general
procedure 100 mg (0.34 mmol) of 1m, 71 mg of 2m (64%
1
yield). White Solid, mp: 154-156 °C. H NMR (400 MHz, CDCl3)
δ = 8.42 (d, J = 8.43 Hz, 1H), 8.33 (Br s, 1H), 7.80 (d, J = 8.19
Hz, 2H), 7.30 ( d, J = 7.82 Hz, 2H), 7.25 (d, J = 1.95 Hz, 1H) 7.20-
7.12 (m, 1H), 2.43 (s, 3H), 1.90-1.81 (m, 4H), 1.64 (s, 1H), 1.43-
1.34 (m, 4H), 1.26 (s, 1H). 13C NMR (100 MHz, CDCl3) δ =
165.16, 145.09, 142.65, 132.46, 131.91, 129.57, 127.11,
126.31, 123.03, 121.59, 43.85, 34.37, 26.79, 26.07, 21.55. ESI-
MS: m/z 328 (M+H) +. ESI-HRMS: calcd for C20H23ONCl =
328.14627, Found 328.14516.
N-(2-chlorophenyl)acetamide (2s):6b The title compound was
prepared according to the general procedure 100 mg (0.74 mmol)
of 1s, 84 mg of 2s (67% yield). White Solid, mp: 90-92 °C. 1H NMR
(400 MHz, CDCl3) δ = 8.32 (d, J = 8.01 Hz, 1H), 7.70 (Br s, 1H), 7.35
(d, J = 8.02 Hz, 1H), 7.27-7.21 (m, 1H), 7.01-6.98 (m, 1H), 2.04 (s,
3H). 13C NMR (100 MHz, CDCl3) δ = 167.43, 133.57, 127.94, 126.70,
123.60, 120.65, 23.84. ESI-MS: m/z 170 (M+H) +.
N-(4-butyl-2-chlorophenyl)-4-methylbenzamide (2n): The title
compound was prepared according to the general procedure
100 mg (0.37 mmol) of 1n, 73 mg of 2n (65% yield). White
1
Solid, mp: 75-77 °C. H NMR (400 MHz, CDCl3) δ = 8.42 (d, J =
(3r,5r,7r)-N-(2-chloro-4-methylphenyl)adamantane-1-carboxamide
8.31 Hz, 1H), 8.34 (Br s, 1H), 7.81 (d, J = 8.19 Hz, 2H), 7.30 (d, J
= 7.94 Hz, 2H), 7.22 (d, J = 1.83 Hz, 1H) 7.16-7.10 (m, 1H), 1.63-
(2t): The title compound was prepared according to the general
1.54 (m, 2H), 1.40-1.30 (m, 2H). 13C NMR (100 MHz, CDCl3) δ = procedure 100 mg (0.31 mmol) of 1t, 73 mg of 2t (65% yield).
White Solid, mp: 156-158 °C. 1H NMR (400 MHz, CDCl3) δ = 8.27 (t, J
165.20, 142.68, 139.86, 132.39, 131.90, 129.58, 128.69,
127.86, 127.11, 122.90, 121.47, 34.98, 33.43, 22.42, 21.56,
+
= 7.9 Hz, 1H), 7.90 (Br s, 1H), 7.15 (dd, J = 13.0, 1.9 Hz, 1H), 7.06 (dd,
J = 8.4, 1.5 Hz, 1H), 2.29 (s, 3H), 2.11 (s, 3H), 2.02-1.90 (m, 6H), 1.83-
1.70 (m, 6H), 13C NMR (100 MHz, CDCl3) δ = 176.01, 134.33, 132.20,
13.95. ESI-MS: m/z 302 (M+H)
. ESI-HRMS: calcd for
C18H21ONCl = 302.13062, Found 302.12963.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Page 6 of 8
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DOI: 10.1039/C8NJ00530C
ARTICLE
Journal Name
Wiley, 1990; (c) Y. Zhang, K. Shibatomi and H. Yamamoto,
Synlett, 2005, 2837; (d) W. D. Watson, J. Org. Chem., 1985,
50, 2145; (e) T. E. Nickson and C. A. Roche-Dolson, Synthesis
(Stuttg)., 1985, 669; (f) H. M. Teeter and E. W. Bell, Org.
Synth., 1952, 32, 20; (g) A. Zanka and A. Kubota, Synlett,
1999, 1999, 1984; (h) I. Lengyel, V. Cesare and R. Stephani,
Synth. Commun., 1998, 28, 1891; (i) V. R. Stimson, Aust. J.
Chem., 1965, 18, 126–127; (j) F. O. Ayorinde, Tetrahedron
Lett., 1983, 24, 2077; (k) G. K. Chip and J. S. Grossert, Can. J.
Chem., 1972, 50, 1233; (l) K. N. Ayad, C. Beard, R. F. Garwood
129.16, 128.33, 122.78, 121.38, 42.03, 39.29, 36.46, 28.17, 20.65.
ESI-MS: m/z 304 (M+H) +.
N-(2-chloro-4-methoxyphenyl)methacrylamide (2u): The title
compound was prepared according to the general procedure
100 mg (0.52 mmol) of 1u, 74 mg of 2u (63% yield). White
1
Solid, mp: 82-84 °C. H NMR (400 MHz, CDCl3) δ = 8.29 (d, J =
9.1 Hz, 1H), 7.90 (Br s, 1H), 6.94 (d, J = 2.8 Hz, 1H), 6.88-6.80
(m, 1H), 5.88 (s, 1H), 5.49 (s, 1H), 3.80 (s, 3H), 2.09 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ = 165.13, 155.23, 139.39, 126.88,
123.07, 121.78, 119.55, 113.52, 112.18, 54.67, 21.76, 17.59.
and W. J. Hickinbottom, J. Chem. Soc. 1957, 0, 2981.
(a) T. K. Macklin and V. Snieckus, Org. Lett., 2005,
(b) W. Lin, O. Baron and P. Knochel, Org. Lett., 2006,
2
7
8
, 2519;
, 5673;
+
(c) E. Marzi, C. Bobbio, F. Cottet and M. Schlosser, Eur. J. Org.
Chem., 2005, 2116.
ESI-MS: m/z 226 (M+H) . ESI-HRMS: calcd for C11H13O2NCl =
226.0635, Found 226.0642.
3
4
K. M. Engle and J.-Q. Yu, J. Org. Chem., 2013, 78, 8927.
R. A. Rodriguez, C.-M. Pan, Y. Yabe, Y. Kawamata, M. D.
Eastgate and P. S. Baran, J. Am. Chem. Soc., 2014, 136, 6908.
(a) M. Liang and J. Chen, Chem. Soc. Rev., 2013, 42, 3453; (b)
D. Tsvelikhovsky and S. L. Buchwald, J. Am. Chem. Soc., 2010,
132, 14048; (c) Y. Zou, J. E. Melvin, S. S. Gonzales, M. J.
N-(2-chlorophenyl)-4-methylbenzenesulfonamide (2v):7 The
title compound was prepared according to the general
procedure 100 mg (0.40 mmol) of 1v, 70 mg of 2v (62% yield).
White Solid, mp: 104-106 °C. 1H NMR (400 MHz, CDCl3) δ =
7.62-7.64 (m, 3H), 7.21-7.27 (m, 4H), 7.05 (d, J = 7.1 Hz, 1H),
7.01 (d, J = 7.0 Hz, 1H), 2.36 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ = 144.27, 135.94, 133.52, 129.71, 129.43, 127.89, 127.30,
125.93, 125.21, 122.49, 21. 59. ESI-MS: m/z 282 (M+H) +.
5
Spafford and A. B. Smith III, J. Am. Chem. Soc., 2015, 137
,
7095; (d) M. Nazaré, C. Schneider, A. Lindenschmidt and D.
W. Will, Angew. Chemie, 2004, 116, 4626; (e) P. C. Fritch, G.
McNaughton-Smith, G. S. Amato, J. F. Burns, C. W. Eargle, R.
Roeloffs, W. Harrison, L. Jones and A. D. Wickenden, J. Med.
Chem., 2009, 53, 887; (f) A. L. Rodriguez, C. Koradin, W.
N-(2-chloro-4-methylphenyl)-4-methylbenzenesulfonamide (2w):19
The title compound was prepared according to the general
procedure 100 mg (0.38 mmol) of 1w, 77 mg of 2w (68% yield).
White Solid, mp: 105-107 °C. 1H NMR (500 MHz, CDCl3) δ = 7.62 (d, J
= 8.39 Hz, 2H), 7.54 (d, J = 8.24 Hz, 1H), 7.20 (d, J = 7.93 Hz, 2H),
7.07-6.99 (m, 2H), 6.85 (s, 1H), 2.37 (s, 3H), 2.25 (s, 3H). 13C NMR
(125 MHz, CDCl3) δ = 143.03, 135.35, 134.95, 129.73, 128.58,
127.55, 126.25, 124.35, 121.99, 20.54, 19.60. ESI-MS: m/z 296
(M+H) +.
Dohle and P. Knochel, Angew. Chemie Int. Ed., 2000, 39
,
2488; (g) Y. J. Jang, H. Yoon and M. Lautens, Org. Lett., 2015,
17, 3895.
(a) X. Wan, Z. Ma, B. Li, K. Zhang, S. Cao, S. Zhang and Z. Shi,
J. Am. Chem. Soc., 2006, 128, 7416; (b) R. B. Bedford, M. F.
Haddow, C. J. Mitchell and R. L. Webster, Angew. Chemie Int.
Ed., 2011, 50, 5524.
6
7
X. Xiong and Y. Yeung, Angew. Chemie Int. Ed., 2016, 55
16101.
X. Bao, J. Yao, H. Zhou and G. Xu, Org. Lett., 2017, 19, 5780.
,
8
9
D. Liang, Y. Li, S. Gao, R. Li, X. Li, B. Wang and H. Yang, Green
Chem., 2017, 19, 3344.
N-(2-Chloro-4-(trifluoromethyl)phenyl)-4-
methylbenzenesulfonamide (2x):19 The title compound was
10 (a) Y. Wang, G. -X. Li, G. Yang, G. He, G. Chen, Chem. Sci.,
2016, 7, 2679; (b) R. Akula, M. Galligan, H. Ibrahim, Chem.
Commun. 2009, 6991; (c) M. Wang, Y. Zhang, T. Wang, C.
Wang, D. Xue and J. Xiao, Org. Lett, 2016, 18, 1976.
11 (a) M. Chandrasekharam, B. Chiranjeevi, K. S. V. Gupta and B.
Sridhar, J. Org. Chem. 2011, 76, 10229; (b) B. Chiranjeevi, G.
Koyyada, S. Prabusreenivasan, V. Kumar, P. Sujitha, C. G.
Kumar, B. Sridhar, S. Shaik and M. Chandrasekharam, RSC
prepared according to the general procedure 100 mg (0.31 mmol)
1
of 1x, 68 mg of 2x (61% yield). White Solid, mp: 94−96 °C. H NMR
(400 MHz, CDCl3) δ = 7.71−7.69 (m, 3H), 7.56 (d, J = 2.1 Hz, 1H), 7.45
(d, J = 8.3 Hz, 1H), 7.30−7.27 (m, 3H), 2.41 (s, 3H). 7.67 (2H, d, J =
8.4 Hz), 7.25−7.23 (m, 3H), 7.13 (d, J = 8.3 Hz, 1H), 6.95 (s, 1H), 6.63-
6.49 (m, 1H), 3.79 (s, 3H), 2.36 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
= 144.87, 136.85, 135.60, 130.16, 127.29, 126.74, 125.21, 123.98,
120.39, 21.62. ESI-MS: m/z 350 (M+H) +.
Adv. 2013,
3, 16475; (c) B. Chiranjeevi, B. Vinayak, T.
Parsharamulu, V. S. Phanibabu, B. Jagadeesh and M.
Chandrasekharam, Eur. J. Org. Chem. 2014, 35, 7839; (d) K. S.
V. Gupta, D. V. Ramana, B. Vinayak, B. Sridhar and M.
Chandrasekharam, New J. Chem. 2016, 40, 6389; (e) V. Botla,
D. V. Ramana, B. Chiranjeevi and M. Chandrasekharam,
Chemistry Select, 2016,
Chandrasekharam, ChemistrySelect, 2017,
1
, 3974; (f) D. V. Ramana and M.
2, 2241; (g) B.
Conflicts of interest
Vinayak and M. Chandrasekharam, Org. Lett, 2017, 19, 3528;
(h) B. Vinayak, P. Navyasree and M. Chandrasekharam, Org.
Biomol. Chem., 2017, 15, 9200; (i) B. Vinayak, A. Ashok and
M. Chandrasekharam, Eur. J. Org. Chem. 2017, 7127; (j) R. V.
There are no conflicts to declare.
Acknowledgements
Daggupati, C. Malapaka, Org. Chem. Front, 2018, 5, 788.
12 (a) T. Piou and T. Rovis, Nature, 2015, 527, 86; (b) J. Li, S.
Warratz, D. Zell, S. De Sarkar, E. E. Ishikawa and L.
Ackermann, J. Am. Chem. Soc., 2015, 137, 13894; (c) K.
Vinayak Botla thanks the University Grant Commission (UGC),
New Delhi for the award of Senior Research Fellowship (SRF).
Raghuvanshi, D. Zell and L. Ackermann, Org. Lett, 2017, 19
,
1278; (d) X.-H. Liu, H. Park, J.-H. Hu, Y. Hu, Q.-L. Zhang, B.-L.
Wang, B. Sun, K.-S. Yeung, F.-L. Zhang and J.-Q. Yu, J. Am.
Chem. Soc, 2017, 139, 888; (e) J. M. Neely and T. Rovis, J.
Notes and references
1
(a) P. Kovacic and A. K. Sparks, J. Am. Chem. Soc., 1960, 82,
5740; (b) R. Taylor, Electrophilic aromatic substitution, J.
6 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C8NJ00530C
Journal Name
ARTICLE
Am. Chem. Soc, 2014, 136, 2735; (f) A. Mandal, H. Sahoo, S.
Dana and M. Baidya, Org. Lett. 2017, 19, 4138.
13 X.-Q. Li and C. Zhang, Synthesis (Stuttg)., 2009, 7, 1163.
14 S. De, J. Yin and D. Ma, Org. Lett., 2017, 19, 4864.
15 P. K. Atanassov, A. Linden and H. Heimgartner, Helv. Chim.
Acta, 2004, 87, 1452.
16 P. A. S. Smith, J. M. Clegg and J. H. Hall, J. Org. Chem., 1958,
23, 524.
17 F. B. Dains,T. H. Vaughan, W. M. Janney, J. Am. Chem.
Soc., 1918, 40, 930.
18 N. Barbero, M. Carril, R. SanMartin, and E. Domınguez,
Tetrahydron, 2007, 63, 10425.
19 J. E. R. Sadig, R. Foster, F. Wakenhut, and M. C. Willis, J. Org.
Chem. 2016, 81, 450.
This journal is © The Royal Society of Chemistry 20xx
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DOI: 10.1039/C8NJ00530C
Revisit of 1-Chloro-1,2-benziodoxol-3-one: Efficient ortho-Chlorination of aryls under
aqueous conditions
.
Botla Vinayak, Pardhi Vishal Ravindrakumar, Daggupati V. Ramana and Malapaka Chandrasekharam*
I&PC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad
The ortho-selective amide directing group assisted chlorination of aryls with easily accessible 1-Chloro-1,2-
benziodoxol-3-one as an oxidant as well as chlorinating reagent, is reported in the absence of radical
initiator. The open air, aqueous conditions and recyclable reagent demonstrate the green principles involved
in the reaction.