Synthesis of 3-halochromones with simple KX halogen sources enabled by: In situ halide oxidation

Article abstract of DOI:10.1039/d0nj00825g

On the basis of a designated in situ oxidation tactic, the synthesis of 3-halochromones has been realized for the first time by using simple KX (X = Br, I) salts as halogen sources. Instead of the free radical process, the control experiments indicate that the reported reactions proceed through a halogenium intermediate. Compared to the known synthetic methods relying on molecular halogen, haloid acid or N-halosuccinimide as the halogen source, the present method is attractive due to its higher atom economy and being more friendly to the operator, thus providing a practical complimentary approach to the preparation of useful halochromone compounds.

Full text of DOI:10.1039/d0nj00825g

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DOI: 10.1039/D0NJ00825G
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Synthesis of 3‐halochromones with simple KX halogen sources
enabled by in situ halide oxidation
Received 00th January 20xx,
Accepted 00th January 20xx
Yan Lin,a Jie‐Ping Wana and Yunyun Liu*,a
DOI: 10.1039/x0xx00000x
On the basis of a designated in situ oxidation tactic, the synthesis of 3‐halochromones has been realized for the first time
by using simple KX (X= Br, I) salts as halogen source. Instead of free radical process, the control experiments indicate that
the reported reactions proceed through halogenium intermediate. Comparing with the known synthetic methods relying
on molecular halogen, haloid acid or N‐halosuccinimide as halogen source, the present method is attractive for the higher
atom economy, and more friendly to operator, thus providing a practical complimentary approach in the preparation of
useful halochromone compounds.
developed the synthesis of 3‐iodochromones via the reactions
of 3‐carbonxylated chromones and molecular iodine.10 Kim
and co‐workers disclosed the synthesis of 3‐bromo‐ and 3‐
Introduction
Chromone is biologically relevant O‐containing heterocycle, it
is well‐known as the central structure of flavone and
isoflavonoid natural products.1 In addition, as privileged
skeleton, chromone also plays pivotal roles in drug discovery
and organic synthesis.2 A variety of chromone derivatives have
been identified with attractive antibacterial activity,3
antitumor activity4 anti‐oxidation activity5 etc. The valuable
application and unexplored functions of chromone has
accordingly triggered significant interests in the research of
chromone synthesis. Over the past decades, splendid advances
have been witnessed in the synthetic research of chromone
synthesis via either direct elaboration on readily available
chromone heterocycle or tandem transformations involving
chromone ring construction and C‐C/C‐heteroatom bond
formation.6
chlorochormones via the C3‐H halogenation of chromone
using HX acid as halogen source.11 In addition, Knochel and co‐
workers reported the switchable synthesis of C2‐ and C3‐
iodinated chromones in the presence of zinc agent.12 Although
the synthesis of 3‐halogchromones are now accessible by
different approaches, one or more of the restrictions remain
to prevent these methods from satisfactory application: a)
using operator unfriendly and toxic molecular halogen such as
Cl2 and Br2 as halogen source; b) transition metal catalysis or
harsh reaction conditions; c) limited availability of the
chromone starting materials. In this context, developing new
methods featuring operator friendly and simple halogen
source, atom economy and step efficiency is yet highly
desirable for the synthesis of 3‐halochormones.
Due to the easy availability and good shelf stability,
enaminones have in recent years displayed amazingly broad
application in the synthesis of diverse organic molecules by
acting as key substrates.13 On the basis of our experience in
such type of synthesis and the fact that halogen anion can be
in situ oxidized to molecular halogen as disclosed by us and
others,14 we envisaged that it is possible to develop step
economical and operator friendly method for 3‐
halochormones synthesis by employing simple and nontoxic
halide salt to react with readily available 2‐hydroxylphenyl
enaminones. Herein, we report our results on the reactions of
2‐hydroxylphenyl enaminones and potassium halides (I and Br)
in the presence of PhI(OAc)2 as a practical method for the
synthesis of 3‐halochromones by employing biomass‐based
available ethyl lactate (EL)15 as green medium.
On the other hand, owing to the versatile and indispensable
application of C‐halogen bond in both organic synthesis and
designation of pharmaceuticals, the synthetic works toward C‐
X bond formation have also received tremendous attention.7
As a class of featured halogenated molecules, the 3‐
halochromones have been identified as indispensable
structures in the synthesis of isoflavonoids and analogous
chromone derivatives.8 Despite the fact that significant
advances have taken place in the synthesis of C3
functionalized chromones, the methods toward the synthesis
of 3‐halochromones are still underdeveloped. In 1979,
Gammill9 reported the synthesis of 3‐halogenated chromones
using molecular halogen as halo‐source. Larrosa et al
Results and discussion
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2
3
4
To start the work, the reaction of enaminone 1a and KI was and 2u, Table 2) and naphthyl functionalized (2e and 2p, Table
View Article Online
DOI: 10.1039/D0NJ00825G
first examined by heating at 80 oC (reflux) in EtOH in the 2) enaminones were evidently lower, suggesting the electron
presence of benzoyl peroxide (BPO), which afforded the target withdrawing effect from induction and conjugation were both
product 2a with 67% yield (entry 1, Table 1). Successive negative to the titled synthesis. Furthermore, KCl was also
experiments in lowering the reaction temperature proved that employed to reaction with 1a under the standard reaction
room temperature was more proper for this reaction (entries conditions, but the 3‐chlorochromone product was not formed
2‐3, Table 1). Subsequently, a series of different oxidants, in the reaction. Notably, conducting the reactions synthesizing
including PhI(OAc)2, K2S2O8, TBHP and DTBP were screened 2a in 5 mmol scale provided good result by affording the
whereby PhI(OAc)2 exhibited the best effect (entries 4‐7, Table product with good yield.
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1). Furthermore, different solvents were independently used
as the medium of this reaction, and the bio‐based green
Table 2 Scope on the synthesis of 3‐halochromonesa,b
solvent EL was found as amongst the best candidate (entries 8‐
16, Table 1). On the other hand, reducing the amount of
PhI(OAc)2 was accompanied with decrease in the yield of 2a
(entry 17, Table 1).
O
O
KX (1 equiv)
PhI(OAc)2 (2 equiv)
EL, r.t.
X
N
R
R
OH
O
2
1
Table 1 Optimization on reaction conditionsa
O
O
O
O
O
I
I
I
I
O
2a, 78% (67%c)
2c, 91%
2b, 68%
O
O
I
O
F
I
O
entry
1
2
3
4
5
6
7
8
oxidant
BPO
BPO
BPO
PhI(OAc)2
K2S2O8
t (oC)
80
60
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EL
MeCN
p‐xylene
DMSO
water
DCM
Yield (%)b
67
73
75
77
trace
45
trace
78
37
43
34
0
41
58
trace
32
O
O
O
2e, 45%
2f, 71%
2d, 86%
O
O
O
I
Cl
I
Br
I
Br
O
O
O
TBHP
DTBP
2g, 74%
2h, 57%
2i, 43%
O
O
O
O
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
NO2
I
Cl
I
Br
9
10
11
12
13
14
15
16
17c
O
O
2j, 31%
2k, 43%
2l, 80%
O
O
O
Br
Br
Br
Br
glycol
THF
dioxane
EL
O
O
O
O
2o, 63%
O
2n, 65%
56
2m, 70%
Br
O
aGeneral conditions: 1a (0.2 mmol), KI (0.2 mmol), oxidant (0.4 mmol) in solvent
(2 mL), stirred under air for 12 h. bYield of isolated product based on 1a. cWith 0.2
mmol PhI(OAc)2.
O
O
Cl
F
Br
O
O
2q, 76%
O
With the satisfactory results from the optimization
experiments, the application scope of this method was
examined by employing different enaminone substrates and
potassium halides. As outlined in Table 2, the present method
displayed general tolerance to the synthesis of 3‐
iodochromones (2a
Table 2). Generally, the enaminones containing alkyl(s) (2b‐2c
and 2m 2n, Table 2), halogen (2f 2i 2k and 2q 2t, Table 1),
nitro (2j and 2u, Table 2) in phenyl ring, the enaminones
functionalized with fused aryl ring (2e and 2p, Table 2) were all
applicable substrates. The majority of products were afforded
with good to excellent yield. However, the yields of the
products resulting from strong electron withdrawing group (2j
2p, 51%
2s, 77%
2r, 72%
O
O
O
Br
Br
Br
NO2
Br
Br
O
O
2t, 57%
‐
2k, Table 2) and 3‐bromochromones (2l
‐
2u
,
2u, 35%
Conditions: 1 (0.2 mmol), KX (0.2 mmol), PhI(OAc)2 (0.4 mmol) in EL (2 mL),
‐
‐
,
‐
stirred under air for 12 h. bYield of isolated product. cThe yield from 5 mmol scale.
In order to explore the reaction mechanism, some control
experiments were conducted. At first, the model reaction was
performed in the presence free radical trapper BHT and
TEMPO, respectively (Eqs 1‐2), and the formation of product
2 | J. Name., 2012, 00, 1‐3
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2a was not inhibited. On the other hand, stirring KI and
PhI(OAc)2 was proved to generate molecular iodine as
observed by the starch test (Eq 3). At last, subjecting
ARTICLE
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Conclusions
View Article Online
DOI: 10.1039/D0NJ00825G
In summary, we have developed a facile method for 3‐
halochromone synthesis by using easily available 2‐
hydroxylphenyl enaminones and potassium halides as starting
materials. The key point enabling such synthesis is the
successful in situ oxidation of halogen anion to molecular
halogen in the presence of PhI(OAc)2 oxidant. In addition to
the facile operation and simple materials, the present
synthetic approach possessing individual advantages of
biomass‐based green medium as well as ambient reaction
conditions. The work thus provides a practical access to
important 3‐halochromones as complementary option to
those known methods.
chromone
3 and KI to the standard condition did not give
product 2a (Eq 4), indicating that the C‐H halogenation takes
place before the chromone annulation. Furthermore, using
only molecular iodine to react with enaminone 1a in EL
provided product 2a with high yield (Eq 5), proving that
molecular iodine was the effective iodo‐source for the
production of 3‐iodochromone.
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standard condition
BHT (3 equiv)
2a
76%
(1)
1a
2a
79%
standard condition
TEMPO (3 equiv)
1a
(2)
(3)
Experimental section
General procedure for the synthesis of products 2
EL, r.t
I2
PhI(OAc)2
KI
positive in
starch test
To a 25 mL round bottom flask were charged with enaminone
(0.2 mmol), KX (X = Br or I, 0.2 mmol), PhI(OAc)2 (0.4 mmol),
O
1
and EL (2 mL). The mixture was then stirred at room
temperature for 12 h. Upon completion, 5 mL of water and 5
mL ethyl acetate was added to the flask, and the resulting
mixture was extracted with ethyl acetate (3 × 8 mL). The
organic phases were collected and dried with anhydrous
Na2SO4. After filtration, the resulting solution was employed to
reduced pressure to remove the solvent. The acquired residue
was subjected to flash silica gel column chromatography to
provide pure products by elution with mixed petroleum
ether/ethyl acetate (v/v = 50:1).
KI
2a
0%
(4)
standard condition
O
3
I2 (1 equiv)
EL, rt
2a
69%
1a
(5)
With the inspiration of the control experiment results, the
reaction mechanism is proposed. As shown in Scheme 1, the
oxidation of KX by oxidant provides molecular halgen, which
Procedure for the scale‐up synthesis of 2a
couples to enaminone
1
via its isomeric form 1’ to yield
by means of electrophilic halogenation.
was generated from and undergoes
To a 50 mL round bottom flask were added enaminone 1a (5
mmol), KI (5 mmol), PhI(OAc)2 (10 mmol), and EL (8 mL). The
mixture was then stirred at room temperature for 12 h. Upon
completion, 15 mL of water and 15 mL ethyl acetate was
added to the flask, and the resulting mixture was extracted
with ethyl acetate (3 × 20 mL). The organic phases were
collected and dried with anhydrous Na2SO4. After filtration, the
resulting solution was employed to reduced pressure to
remove the solvent. The resulting residue was purified by silica
gel flash column chromatography by using mixed petroleum
ether and ethyl acetate (v/v = 50/1) as eluent to provide pure
product.
halogenated species
The halogenium ion
4
5
4
intramolecular attack by the hydroxyl leads to the formation of
intermediate , which gives rise to 3‐halochromones via the
6
2
elimination of dimethylamine.
PhI(OAc)2
X2
O
O
X
N
N
N
R
R
OH
OH
O
1
1'
O
3‐Iodo‐4H‐chromen‐4‐one (
2a).7f Yield 78% (42.4 mg); white
X
o
1
R
solid; mp 88‐89 C; H NMR (400 MHz, CDCl3): δ 8.30 (s, 1 H),
8.23 (d, J = 8.0 Hz, 1 H), 7.71 (t, J = 7.8 Hz, 1 H), 7.48‐7.42 (m, 2
H); 13C NMR (100 MHz, CDCl3): 173.3, 157.7, 156.1, 134.1,
126.6, 125.9, 121.8, 118.0, 86.8.
R
R
OH
X
N
O
OH
5
H
4
O
3‐Iodo‐6‐methyl‐4H‐chromen‐4‐one (
2b).8a Yield 68% (38.8
H
o
1
X
mg); white solid; mp 130‐131 C; H NMR (400 MHz, CDCl3): δ
8.26 (s, 1 H), 7.99 (s, 1 H), 7.50 (dd, J = 8.6, 2.0 Hz, 1 H), 7.35 (d,
J = 8.6 Hz, 1 H), 2.45 (s, 3 H); 13C NMR (100 MHz, CDCl3): 173.3,
157.6, 154.4, 136.0, 135.3, 125.8, 121.5, 117.7, 86.6, 21.
X
R
O
N
O
HN(CH3)2
2
6
3‐Iodo‐6,7‐dimethyl‐4H‐chromen‐4‐one (
2c).9 Yield 91% (54.6
Scheme 1 The plausible reaction mechanism
o
1
mg); white solid; mp 156‐157 C; H NMR (400 MHz, CDCl3): δ
8.21 (s, 1 H), 7.92 (s, 1 H), 7.20 (s, 1 H), 2.36 (s, 3 H), 2.34 (s, 3
This journal is © The Royal Society of Chemistry 20xx
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H); 13C NMR (100 MHz, CDCl3): 173.2, 157.4, 154.7, 144.7, 8.20 (s, 1 H), 8.02 (s, 1 H), 7.51 (dd, J = 8.6, 2.2 Hz,V1iewHA),rti7cl.e3O7n(lidne,
135.4, 126.0, 119.6, 118.0, 86.7, 20.5, 19.4.
J = 8.6 Hz, 1 H), 2.46 (s, 3 H); 13C NMR (1D00OIM: 10H.1z0,3C9D/DC0l3N)J:0107822.52G,
3‐Iodo‐7‐methoxy‐4H‐chromen‐4‐one (
2d).8c Yield 86% (51.9 154.3, 153.7, 136.0, 135.4, 125.6, 122.8, 117.9, 110.4, 20.9;
o
1
mg); white solid; mp 157‐158 C; H NMR (400 MHz, CDCl3): δ ESI‐HRMS Calcd for C10H8BrO2 [M + H]+ 238.9702, found
8.21 (s, 1 H), 8.13 (d, J = 9.0 Hz, 1 H), 6.99 (dd, J = 8.8, 2.4 Hz, 1 238.9699.
H), 6.83 (d, J = 2.4 Hz, 1 H), 3.91 (s, 3 H); 13C NMR (100 MHz, 3‐Bromo‐6,7‐dimethyl‐4
CDCl3): 172.6, 164.3, 157.9, 157.2, 128.1, 115.7, 115.3, 100.1, (32.8 mg); white solid; mp 141‐142 C; H NMR (400 MHz,
H
‐chromen‐4‐one
(
2n). Yield 65%
o
1
87.2, 55.9.
3‐Iodo‐4 ‐benzo[h]chromen‐4‐one
CDCl3): δ 8.16 (s, 1 H), 7.96 (s, 1 H), 7.22 (s, 1 H), 2.38 (s, 3 H),
10
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12
13
14
15
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49
50
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52
53
54
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57
58
59
60
H
(
2e). Yield 45% (29.2 mg); 2.35 (s, 3 H); 13C NMR (100 MHz, CDCl3): 172.1, 154.6, 153.4,
o
1
white solid; mp 166‐167 C; H NMR (400 MHz, CDCl3): δ 8.42 144.8, 135.3, 125.8, 121.0, 118.1, 110.4, 20.4, 19.3; ESI‐HRMS
(s, 1 H), 8.38 (d, J = 8.2 Hz, 1 H), 8.11 (d, J = 8.8 Hz, 1 H), 7.90 (d, Calcd for C11H10BrO2 [M + H]+ 252.9859, found 252.9855.
J = 8.0 Hz, 1 H), 7.77‐7.64 (m, 3 H); 13C NMR (100 MHz, CDCl3): 3‐Bromo‐7‐methoxy‐4
H‐chromen‐4‐one (2o). Yield 63% (32.2
o
1
173.0, 156.8, 153.6, 135.8, 129.7, 128.2, 127.4, 126.1, 123.5, mg); white solid; mp 184‐185 C; H NMR (400 MHz, CDCl3): δ
122.2, 121.2, 118.0, 88.9; ESI‐HRMS Calcd for C13H8IO2 [M + H]+ 8.16 (d, J = 7.4 Hz, 2 H), 7.03‐6.98 (m, 1 H), 6.84 (d, J = 2.2 Hz, 1
322.9563, found 322.9558.
6‐Fluoro‐3‐iodo‐4 ‐chromen‐4‐one
H), 3.91 (s, 3 H); 13C NMR (100 MHz, CDCl3): 171.5, 164.4, 157.9,
H
(
2f).2a Yield 71% (41.2 mg); 153.2, 127.8, 117.0, 115.3, 110.8, 100.2, 55.9; ESI‐HRMS Calcd
o
1
white solid; mp 123‐124 C; H NMR (400 MHz, CDCl3): δ 8.30 for C10H8BrO3 [M + H]+ 254.9651, found 254.9647.
(s, 1 H), 7.92‐7.81 (m, 1 H), 7.53‐7.39 (m, 2 H); 13C NMR 3‐Bromo‐4
H‐benzo[h]chromen‐4‐one (2p). Yield 51% (27.9
(100MHz, CDCl3): 172.8, 159.8 (d, 1JC‐F = 247 Hz), 157.9, 152.4, mg); yellow solid; mp 133‐134 oC; 1H NMR (400 MHz, CDCl3): δ
122.8 (d, 3JC‐F = 8 Hz), 122.5 (d, 2JC‐F = 25 Hz), 120.3 (d, 3JC‐F = 8 8.42 (d, J = 8.2 Hz, 1 H), 8.38 (s, 1 H), 8.15 (d, J = 8.8 Hz, 1 H),
Hz), 111.4 (d, 2JC‐F = 24 Hz), 86.0.
6‐Chloro‐3‐iodo‐4 ‐chromen‐4‐one
7.92 (d, J = 8.0 Hz, 1 H), 7.78 (d, J = 8.8 Hz, 1 H), 7.73 (t, J = 7.2
H
(
2g). Yield 74% (45.3 mg); Hz, 1 H), 7.68 (t, J = 7.6 Hz, 1 H); 13C NMR (100 MHz, CDCl3):
o
1
white solid; mp 145‐146 C; H NMR (400 MHz, CDCl3): δ 8.30 172.0, 153.6, 152.9, 135.8, 129.7, 128.2, 127.5, 126.1, 123.6,
(s, 1 H), 8.18 (d, J = 2.4 Hz, 1 H), 7.65 (dd, J = 8.8, 2.4 Hz, 1 H), 122.2, 121.0, 119.4, 112.4; ESI‐HRMS Calcd for C13H8BrO2 [M +
7.44 (d, J = 8.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3): 172.3, H]+ 274.9702, found 274.9697.
157.8, 154.5, 134.4, 131.8, 125.9, 122.5, 119.8, 86.6; ESI‐HRMS 3‐Bromo‐6‐fluoro‐4H‐chromen‐4‐one
(
2q). Yield 76% (36.7
mg); white solid; mp 134‐135 C; H NMR (400 MHz, CDCl3): δ
2h). Yield 57% (40.1 mg); 8.25 (s, 1 H), 7.88 (dd, J = 8.2, 3.0 Hz, 1 H), 7.52 (dd, J = 9.2, 4.2
white solid; mp 163‐164 C; H NMR (400 MHz, CDCl3): δ 8.26 Hz, 1 H), 7.48‐7.42 (m, 1 H); 13C NMR (100 MHz, CDCl3): 171.5,
o
1
Calcd for C9H5ClIO2 [M + H]+ 306.9017, found 306.9013.
6‐Bromo‐3‐iodo‐4 ‐chromen‐4‐one
H
(
o
1
1
3
(s, 1 H), 8.09 (d, J = 8.4 Hz, 1 H), 7.66 (d, J = 1.6 Hz, 1 H), 7.56 159.8 (d, JC‐F = 247 Hz), 153.9, 152.3, 124.2 (d, JC‐F = 8 Hz),
(dd, J = 8.4, 1.6 Hz, 1 H); 13C NMR (100 MHz, CDCl3): 172.6, 122.5 (d, 2JC‐F = 25 Hz), 120.4 (d, 3JC‐F = 8 Hz), 111.2 (d, 2JC‐F = 24
157.6, 156.1, 129.6, 128.5, 128.0, 121.1, 120.5, 87.1; ESI‐HRMS Hz), 110.1; ESI‐HRMS Calcd for C9H5BrFO2 [M + H]+ 242.9451,
Calcd for C9H5BrIO2 [M + H]+ 350.8512, found 350.8507.
7‐Bromo‐3‐iodo‐4 ‐chromen‐4‐one
found 242.9448.
2i). Yield 43% (30.2 mg); 3‐Bromo‐6‐chloro‐4H‐chromen‐4‐one (2r). Yield 72% (37.2
H
(
o
1
o
1
white solid; mp 163‐164 C; H NMR (400 MHz, CDCl3): δ 8.26 mg); white solid; mp 128‐129 C; H NMR (400 MHz, CDCl3): δ
(s, 1 H), 8.09 (d, J = 8.6 Hz, 1 H), 7.66 (d, J = 1.8 Hz, 1 H), 7.56 8.23 (s, 1 H), 8.22 (d, J = 2.6 Hz, 1 H), 7.65 (dd, J = 9.0, 2.6 Hz, 1
(dd, J = 8.6, 1.6 Hz, 1 H); 13C NMR (100 MHz, CDCl3): 172.6, H), 7.46 (d, J = 8.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3): 171.1,
157.6, 156.1, 129.6, 128.5, 128.0, 121.1, 120.6, 87.1; ESI‐HRMS 154.4, 153.9, 134.4, 131.9, 125.7, 124.0, 119.9, 110.6; ESI‐
Calcd for C9H5BrIO2 [M + H]+ 350.8512, found 350.8507.
HRMS Calcd for C9H5BrClO2 [M + H]+ 258.9156, found 258.9152.
‐chromen‐4‐one 2s). Yield 77% (46.5 mg);
3‐Iodo‐6‐nitro‐4 ‐chromen‐4‐one 2j). Yield 31% (19.7 mg); 3,6‐Dibromo‐4
H
(
H
(
white solid; mp 93‐94 oC; 1H NMR (400 MHz, DMSO‐d6): δ 8.93 white solid; mp 141‐142 C; H NMR (400 MHz, CDCl3): δ 8.36
(s, 1 H), 8.73 (d, J = 2.8 Hz, 1 H), 8.58 (dd, J = 9.2, 2.8 Hz, 1 H), (d, J = 2.2 Hz, 1 H), 8.24 (s, 1 H), 7.79 (dd, J = 8.8, 2.2 Hz, 1 H),
7.94 (d, J = 9.2 Hz, 1 H); 13C NMR (100 MHz, DMSO‐d6): 172.8, 7.39 (d, J = 8.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3): 170.9,
160.2, 159.1, 145.1, 129.1, 122.1, 121.4, 121.2, 87.6; APCI‐ 154.8, 153.9, 137.2, 128.9, 124.3, 120.1, 119.3, 110.7; APCI‐
o
1
HRMS Calcd for C9H5INO4 [M + H]+ 317.9258, found 317.9253.
HRMS Calcd for C9H5Br2O2 [M + H]+ 302.8651, found 302.8648.
‐chromen‐4‐one 2t). Yield 57% (34.4 mg);
6‐Chloro‐3‐iodo‐7‐methyl‐4 ‐chromen‐4‐one
H
(
2k).8a Yield 43% 3,7‐Dibromo‐4
H
(
o
1
o
1
(27.5 mg); white solid; mp 167‐168 C; H NMR (400 MHz, white solid; mp 143‐144 C; H NMR (400 MHz, CDCl3): δ 8.20
CDCl3): δ 8.25 (s, 1 H), 8.16 (s, 1 H), 7.34 (s, 1 H), 2.50 (s, 3 H); (s, 1 H), 8.12 (d, J = 8.6 Hz, 1 H), 7.68 (d, J = 1.6 Hz, 1 H), 7.58
13C NMR (100 MHz, CDCl3): 172.1, 157.6, 154.4, 143.6, 132.6, (dd, J = 8.6, 1.6 Hz, 1 H); 13C NMR (100 MHz, CDCl3): 171.5,
126.1, 120.7, 119.7, 86.5, 20.9.
3‐Bromo‐4 ‐chromen‐4‐one
156.0, 153.6, 129.6, 128.5, 127.8, 121.9, 121.2, 111.0; APCI‐
H
(
2l).7f Yield 80% (35.8 mg); white HRMS Calcd for C9H5Br2O2 [M + H]+ 302.8651, found 302.8647.
o
1
solid; mp 94‐95 C; H NMR (400 MHz, CDCl3): δ 8.27 (dd, J = 3‐Bromo‐6‐nitro‐4H‐chromen‐4‐one (2u). Yield 35% (18.7 mg);
8.0, 1.6 Hz, 1 H), 8.24 (s, 1 H), 7.74‐7.70 (m, 1 H), 7.50‐7.44 (m, white solid; mp 110‐111oC; H NMR (400 MHz, DMSO‐d6): δ
1
2 H); 13C NMR (100 MHz, CDCl3): 172.2, 156.1, 153.8, 134.1, 8.99 (s, 1 H), 8.74 (d, J = 2.8 Hz, 1 H), 8.59 (dd, J = 9.2, 2.8 Hz, 1
126.4, 125.9, 123.1, 118.1, 110.7.
3‐Bromo‐6‐methyl‐4 ‐chromen‐4‐one
H), 7.96 (d, J = 9.2 Hz, 1 H); 13C NMR (100 MHz, DMSO‐d6):
2m). Yield 70% (33.3 171.2, 159.0, 156.7, 145.1, 129.1, 122.9, 121.9, 121.4, 110.4;
H
(
o
1
mg); white solid; mp 98‐99 C; H NMR (400 MHz, CDCl3): δ
4 | J. Name., 2012, 00, 1‐3
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APCI‐HRMS Calcd for C9H5BrNO4 [M + H]+ 269.9396, found
269.9392.
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Conflicts of interest
There are no conflicts to declare.
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DOI: 10.1039/D0NJ00825G
TOC
O
O
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PhI(OAc)2
NMe2
X
KX
R
R
EL, rt
OH
O
X = Br, I
21 examples
Step efficient
Green medium
Ambient conditions
Simple starting materials
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The in situ oxidation generating molecular halogen strategy has been developed for
the synthesis of 3-halochromones by employing simple potassium halides as halogen
source. The reactions feature advantages of step efficiency, green medium, ambient
conditions and simple starting materials.