Synthesis of dibromo ketones by the reaction of the environmentally benign H2O2-HBr system with oximes

Article abstract of DOI:10.2478/s11532-011-0158-8

It was found that oximes undergo deoximation in the presence of the H2O2aq-HBraq system to form ketones and bromo ketones. This reaction provided the basis for the synthesis of dibromo ketones in yields varying from 40% to 94%. This method is environmentally friendly, sustainable, and easy to perform. The results of this investigation extend the potential of the use of oximes for the protection of carbonyl group, thus offering the ability to perform not only conventional deoximation but also the subsequent bromination of ketones. The reaction is easily scaled up and dibromo ketones can be prepared in gram amounts. Versita Sp. z o.o.

Full text of DOI:10.2478/s11532-011-0158-8

Cent. Eur. J. Chem. • 10(2) • 2012 • 360-367
DOI: 10.2478/s11532-011-0158-8
Central European Journal of Chemistry
Synthesis of dibromo ketones
by the reaction of the environmentally
benign H2O2-HBr system with oximes
Research Article
Alexander O. Terent’ev1*, Igor B. Krylov1, Vera A. Vil’1,
Zhanna Yu. Pastukhova1, Sergey A. Fastov2, Gennady I. Nikishin1
1N. D. Zelinsky Institute of Organic Chemistry,
Russian Academy of Sciences, 119991 Moscow, Russian Federation
2JSC “Nano Technology and Innovations”,
124482 Zelenograd, Russian Federation
Received 6 October 2011; Accepted 27 November 2011
Abstract:
It was found that oximes undergo deoximation in the presence of the H2O2aq-HBraq system to form ketones and bromo ketones.
This reaction provided the basis for the synthesis of dibromo ketones in yields varying from 40% to 94%. This method
is environmentally friendly, sustainable, and easy to perform. The results of this investigation extend the potential of the use of oximes
for the protection of carbonyl group, thus offering the ability to perform not only conventional deoximation but also the subsequent
bromination of ketones. The reaction is easily scaled up and dibromo ketones can be prepared in gram amounts.
Keywords: Oximes • Dibromo ketones • Bromination • Hydrogen peroxide • Hydrobromic acid
© Versita Sp. z o.o.
1. Introduction
in which dibromo ketones 4a-l are formed as the major
reaction products (Scheme 1).
Oximes belong to one of the most important classes of
This result was quite unpredictable. We expected
compounds in organic chemistry. Due to their availability that the reaction would afford geminal bromo nitroso
and diverse reactivity, these compounds are used in and bromo nitro products in view of the fact that, as
the synthesis of amines, amides (lactams), nitriles, halo shown earlier, the reactions of oximes with the related
nitroso derivatives and halo nitro derivatives, as complex- H2O2-HCl system performed under similar conditions
forming agents, chelating agents, etc.
(AcOH, dioxane, benzene, and dichloromethane as
The oximation of the carbonyl group is a convenient the solvents; 38-50°C) give geminal chloronitroso and
way of protecting this group; numerous procedures for chloronitro products with a good selectivity and in high
the deoximation were described in the literature [1]. yields (Scheme 2) [2].
All these procedures are, as a rule, limited to the formation
of the starting carbonyl compounds from oximes.
It should be noted that, since in comparison with
elemental halogens the H2O2-HHal systems are non-
In the present study, we show that oximes 1 can hazardous, environmentally friendly, and easy to
be used as the starting reagents for the synthesis of produce, their use follows modern trends in organic
bromo ketones 3-5 (apparently, through the intermediate synthesis and these systems were widely used in the
formation of ketones 2) by performing the reaction of last decades [3-7]. These systems are most extensively
1 with the H2O2aq-HBraq reaction system. The latter is used for halogenation of arenes [4], alkenes [5], ketones
non-hazardous and convenient to handle and it acts as [6], and alkylarenes [7]. The diversity of halogenation
the deoximating and brominating agent with respect to and oxidation reactions associated with the generation
oximes 1a-l. We found the conditions of the synthesis, of several active species (HHalO, H2HalO+, Hal2) in the
* E-mail: terentev@ioc.ac.ru
360

A. O. Terent’ev et al.
NOH
O
O
O
O
Br
Br
Br
Br
H2O2aq - HBraq
Br
+
R'
+
R'
R'
R'
+
R'
R''
Br
R''
1a-l
R''
R''
2h
3h
4a-l
5h
a: R' = Ph, R'' = H; b: R' = 2-naphtyl, R'' = H; c: R' = R'' = 2-tetralin; d: R' = 4-MeC6H4, R'' = H;
e
f
g
: R' = 4-MeC6H4, R'' = H; : R' = 4-HOC6H4, R'' = H; : R' = 4-ClC6H4, R'' = H;
h: R' = 4-BrC6H4, R'' = H; i: R' = 3-BrC6H4, R'' = H; j: R' = 3-NO2C6H4, R'' = H;
k
l
: R' = 4-NO2C6H4, R'' = H; : R' = tert-butyl, R'' = H
Scheme 1. Transformations of oximes 1a-l in reactions with the H2O2-HBr system.
Scheme 2. Chlorination of oximes with an H2O2-HCl system: facile synthesis of gem-chloronitroso- and gem-chloronitro compounds.
H2O2-HHal systems [8] offers the ability to control the of 1 equiv of the corresponding ketone, 2.3 equiv of
pathway and selectivity of the reactions. hydroxylamine hydrochloride, and 2.5 equiv of sodium
The results of this investigation extend the potential acetate trihydrate in aqueous methanol. Their purities
of the application of oximes for the protection of the were confirmed by measuring the melting points and
carbonyl group, thus offering the ability to perform not NMR spectra.
only conventional deoximation but also the subsequent
Dioxane, AcOH, MeCN, CHCl3, CH2Cl2, PhH, and
bromination of ketones. This approach can be useful petroleum ether (PE, 40-70) of high purity grade were
in a multistage synthesis in which oxime fragment is used as is from commercial sources.
introduced temporarily for the protection of carbonyl
Synthesisof2,2-dibromo-3,4-dihydronaphthalen-
group or prepared not from the carbonyl group as well 1(2H)-one, 4с.
as in transformations, which are possible only in the
presence of the oxime group.
3,4-Dihydro-1(2H)-naphthalenone
oxime
1c
(200 mg, 1.24 mmol) was dissolved in CH3COOH
(3.5 mL). Then a 36% aqueous H2O2 solution (469 mg,
4.96 mmol) and a 48% aqueous HBr solution (2.09 g,
12.4 mmol) were successively added with cooling on
a water bath to 15-20°С. The reaction mixture was
2. Experimental procedure
The NMR spectra were recorded on Bruker AМ-300 refluxed for 20 min (96-106°С) and then cooled to
1
(300.13 MHz for Н and 75.48 MHz for 13С), Bruker room temperature. Water (20 mL) was added, and the
1
WM-250 (250.13 MHz for Н and 62.9 MHz for 13С), reaction products were extracted with CHCl3 (2×10 mL).
and Bruker AC-200 (200.13 MHz for 1Н and 50.32 MHz The combined organic extracts were washed with water
for 13С) spectrometers in СDCl3. The TLC analysis was (2×20mL), driedoverNa2SO4, filtered, andconcentrated.
carried out on chromatographic Silufol UV-254 plates. 2,2-Dibromo-3,4-dihydronaphthalen-1(2H)-one 4c was
Column chromatography was performed with the use of isolated by column chromatography on SiO2 with the
63-200 mesh silica gel (Merk).
The melting points were determined on a Kofler hot (272 mg, 0.893 mmol).
stage and are uncorrected.
Synthesis of
Ketones and hydroxylamine hydrochloride were ethanone, 4b.
commercial reagents (Acros). An aqueous 36% H2O2
1-(2-Naphthalenyl)-1-ethanone oxime 1b (200 mg,
use of CH2Cl2/PE = 1/1 as the eluent; the yield was 72%
2,2-dibromo-1-(2-naphthyl)
solution and an aqueous 48% HBr solution of high 1.08 mmol) was dissolved in dioxane (3 mL). Then a
purity grade were used without additional purification. 36% aqueous H2O2 solution (408 mg, 4.32 mmol) and
All oxime substrates 1a-l used in this investigation a 48% aqueous HBr solution (1.82 g, 10.8 mmol) were
were quantitatively synthesized by refluxing a mixture successively added with cooling on a water bath to
361

Synthesis of dibromo ketones by the reaction
of the environmentally benign H2O2-HBr system with oximes
15-20°С. The reaction mixture was refluxed for 20 min ArH), 7.49-7.57 (m, 1H, ArH) 8.09-8.16 (m, 1H, ArH).
(89-92°С) and then cooled to room temperature. Water
(20 mL) was added, and the reaction products were 126.9, 127.0, 128.5, 129.8, 134.3, 141.9, 183.9.
13С NMR (50.32MHz, CDCl3): δ = 29.1, 45.6, 67.4,
extracted with CHCl3 (2×10 mL). The combined organic
extracts were washed with water (2×20 mL), dried [12]
over Na2SO4, filtered, and concentrated. 2,2-Dibromo-
2,2-Dibromo-1-(4-methylphenyl)ethanone
(4d)
Pale yellow crystals; mp = 97-98°C ([12] mp 98-
1-(2-naphthyl)ethanone 4b was isolated by column 99°C).
chromatography on SiO2 with the use of CH2Cl2/PE =
1H NMR (250.13MHz, CDCl3): δ = 2.43 (s, 3Н, CH3),
4/3 as the eluent; the yield was 83% (294 mg, 0.896 6.72 (s, 1Н, CH), 7.30 (d, 2H, J = 7.9 Hz, ArH), 7.97 (d,
mmol).
Synthesis
mixture of meso- and rac-isomers (7).
2Н, J = 7.9 Hz, ArH).
2,2-Dibromo-1-(3-bromo-4-methoxyphenyl)
ethanone (4e) [6b]
of
5,7-dibromo-undecan-6-one,
Undecan-6-one oxime 6 (200 mg, 1.08 mmol) was
Slightly yellow crystals; mp = 103-104°C ([6b] 104-
dissolved in dioxane (3 mL). Then a 36% aqueous H2O2 105°C)
solution (306 mg, 3.24 mmol) and a 48% aqueous HBr
1H NMR (200.13MHz, CDCl3): δ = 3.98 (s, 3H, CH3),
solution (1.28 g, 7.59 mmol) were successively added 6.63 (s, 1Н, CH), 6.96 (d, 1H, J = 8.7 Hz, ArH), 8.10 (dd,
with cooling on a water bath to 15-20°С. The reaction 1H, J = 8.7, 2.3 Hz, ArH), 8.30 (d, 1H, J = 2.3 Hz, ArH).
mixture was refluxed for 20 min (89-92°С) and then 13С NMR (50.32MHz, CDCl3): δ = 39.5, 56.7, 111.3,
cooled to room temperature. The isolation was carried 112.3, 124.2, 131.1, 135.0, 160.5, 183.7.
out as described in previous experiment. The yield
of 5,7-dibromo-undecan-6-one 7 was 76% (269 mg, ethanone (4f) [6b]
0.82 mmol). White crystals; mp = 104.5-105°C ([6b] 104-105°C)
4’-Bromoacetophenone (2h) [9]
1H NMR (250MHz, CDCl3): δ = 6.54 (s, 1Н, CH),
2,2-Dibromo-1-(3,5-dibromo-4-hydroxyphenyl)
1H NMR (300.13 MHz, CDCl3): δ = 2.54 (s, 3H, CH3), 6.43-6.55 (br.s., 1H, OH), 8.24 (s, 2H, ArH).
7.56 (d, J = 8.4 Hz, 2H, CH), 7.80 (d, J = 8.4 Hz, 2H,
CH).
13С NMR (62.9MHz, CDCl3): δ = 38.7, 110.3, 125.3,
134.1, 154.5, 182.7.
13C NMR (75.47 MHz, CDCl3): δ = 26.5, 128.2, 129.8,
131.8, 135.8, 197.0.
2,2-Dibromo-1-(4-chlorophenyl)ethanone
[12]
White crystals; mp = 92.5-93.5°C ([12] mp 93-
94°C).
1H NMR (200.13MHz, CDCl3): δ = 6.62 (s, 1Н, CH),
7.48 (d, 2H, J = 8.5 Hz, ArH), 8.04 (d, 2H, J = 8.5 Hz,
(4g)
2-Bromo-1-(4-bromophenyl)ethanone (3h) [10]
White crystals; mp = 106-108°C ([10] mp 107 - 110°C).
1H NMR (300.13 MHz, CDCl3): δ = 4.4 (s, 2H), 7.65
(m, 2H, CH), 7.86 (m, 2H, CH).
13C NMR (75.47 MHz, CDCl3): δ = 30.1, 129.1, 130.2, ArH).
132.0, 132.3, 190.2.
2,2-Dibromo-1-(4-bromophenyl)ethanone
[12]
(4h)
2,2-Dibromo-1-phenylethanone (4a) [11]
White crystals; mp = 35-36°C ([11] mp 35.5-36°C).
1H NMR (250MHz, CDCl3): δ = 6.74 (s, 1Н, CH),
White crystals; mp = 92-93 °C ([12] mp 93-94°C).
1H NMR (250.13MHz, CDCl3): δ = 6.61 (s, 1Н, CH),
7.46-7.59 (m, 2H, ArH), 7.59-7.70 (m, 1Н, ArH), 8.09 7.65 (d, 2H, J = 8.7Hz, ArH), 7.97 (d, 2H, J = 8.7Hz,
(m, 2H, ArH). ArH).
2,2-Dibromo-1-(2-naphthyl)ethanone (4b) [12]
13С NMR (75.47MHz, CDCl3): δ = 39.4, 129.7, 129.9,
Pale yellow crystals; mp = 100-101.5°C ([12] mp 101- 131.2, 132.3, 185.1).
102°C). 2,2-Dibromo-1-(3-bromophenyl)ethanone
1H NMR (250MHz, CDCl3): δ = 6.89 (s, 1Н, CH), [14]
(4i)
7.55-7.70 (m, 2H, ArH), 7.86-8.01 (m, 3H, ArH), 8.06-
8.11 (m, 1H, ArH), 8.62 (s, 1H, ArH).
Pale yellow crystals; mp = 42.5-44°C ([14] mp 43-
44°C).
1H NMR (250MHz, CDCl3): δ = 6.65 (s, 1Н, CH),
13С NMR (62.9MHz, CDCl3): δ = 39.9, 124.7, 127.2,
127.9, 128.1, 128.9, 129.5, 129.8, 131.8, 132.2, 136.0, 7.37 (m, 1H, ArH), 7.75 (m, 1H, ArH), 8.01 (m, 1H, ArH),
186.0.
2,2-Dibromo-3,4-dihydronaphthalen-1(2H)-one
(4c) [13]
White crystals; mp =57-59°C ([13] mp 59-60°C)
1H NMR (300.13MHz, CDCl3): δ = 2.95-3.15 (m, 4H,
CH2-CH2), 7.22-7.29 (m, 1H, ArH), 7.30-7.40 (m, 1H, 56°C).
8.20 (m, 1H, ArH).
13С NMR (62.9MHz, CDCl3): δ = 39.6, 123.2, 128.2,
130.3, 132.5, 134.4, 137.3, 184.7.
2,2-Dibromo-1-(3-nitrophenyl)ethanone (4j) [12]
Pale yellow crystals; mp = 55-56 °C ([12] mp 55-
362

A. O. Terent’ev et al.
1H NMR (300.13 MHz, CDCl3): δ =6.66 (s, 1H, CH), on the reaction conditions, acetophenone 2h and
7.76 (m, 1H, ArH), 8.42-8.55 (m, 2H, ArH), 8.94 (s, 1H, consecutivelybrominatedmonobromoacetophenone3h,
ArH).
dibromoacetophenone 4h, and tribromoacetophenone
13C NMR (75.47 MHz, CDCl3): δ = 38.7, 124.8, 128.6, 5h were prepared (Table 1).
130.3, 132.2, 135.4, 148.5, 148.1.
The influence of the following three parameters on
the yield of products 2h-5h was examined: the nature of
the solvent and the amounts of H2O2 and HBr.
Inruns1-9,whereaceticacidwasusedasthesolvent,
the amounts of H2O2 and HBr were optimized with the aim
of achieving selective deoximation and preparing one of
2,2-Dibromo-1-(4-nitrophenyl)ethanone (4k) [15]
Pale yellow crystals; mp = 62-64°C ([15] mp 60°C).
1H NMR (300.13 MHz, CDCl3): δ = 6.62 (s, 1Н, CH),
8.22-8.41 (m, 4H, ArH).
1,1-Dibromo-3,3-dimethylbutan-2-one (4l) [16]
1H NMR (300.13 MHz, CDCl3): δ = 1.29 (s, 9H, bromoacetophenones. It was shown that the reaction
3CH3), 6.34 (s, 1H, CH).
affords mono- (3h) and dibromoacetophenone 4h as the
13C NMR (75.47 MHz, CDCl3): δ = 26.5 (CH3), 37.0, major reaction products as the amount of H2O2 increases
43.7, 201.2 (C=O)
from 0.5 to 2.5 mol per mole of 1h in the presence of
an excess of HBr varying from 3 to 10 mol per mole of
1h (runs 1-7). In runs 6 and 7, dibromoacetophenone
2,2,2-Tribromo-1-(4-bromophenyl)ethanone (5h)
Slightly yellow solid; mp = 104-105°C.
1H NMR (300.13 MHz, CDCl3): δ = 7.63 (d, 2H, CH, 4h was prepared with selectivity, allowing the use of
1,2 = 8.81 Hz), 8.21 (d, 2H, CH, J1,2 = 8.81 Hz). this procedure for synthetic purposes. A comparison of
13С NMR (75.47 MHz, CDCl3): δ = 41.3, 127.1, 129.5, the results of runs 5-7 showed that an excess of HBr
131.7, 133.3, 180.7. suppresses the bromination reaction to a certain extent.
Anal. Calcd for C8H4Br4O: C, 22.05; H, 0.93; Br, This is consistent with the data on the reversibility of the
J
73.35. Found: C, 22.15; H, 0.95; Br, 73.38.
5,7-Dibromo-undecan-6-one, mixture of meso-
and rac-isomers (7) [17]
bromination of ketones [18].
In run 8 (in the absence of HBr), acetophenone 2h
was obtained in good yield (80%); the H2O2 – AcOH
system acts as the deoximating agent.
Slightly yellow oil.
1H NMR (300.13 MHz, CDCl3): δ = 0.92 (m, 6H,
An unexpected result was obtained in run 9, where
CH3), 1.26-1.56 (m, 8H, CH2), 1.89-2.25 (m, 4H, CH2), H2O2 was not used as the oxidizing agent; instead, air
4.58 (m, 0.5H, CHBr), 4.72 (m, 1.5H, CHBr).
was bubbled through the reaction mixture and, as a
13С NMR (75.47 MHz, CDCl3): δ = 13.9 (CH3), 22.1, result, monobromoacetophenone 3h was synthesized
22.3, 29.4, 29.5, 32.4, 34.5 (CH2), 50.3, 50.7 (CHBr), as the major product (yield 66%). It is known that HBr is
194.4, 197.9 (CO).
not oxidized by atmospheric oxygen; however, arenes,
alkenes, and ketones can be brominated by the HBr/
NaNO2/air system.[3a,19] Presumably, in the case under
consideration HBr is oxidized by nitrogen oxides that are
formed in the course of deoximation of oxime.
The use of dioxane as the solvent (runs 10-12)
allowed us to prepare monobromoacetophenone 3h
(run 11) and dibromoacetophenone 4h (run 12) in
satisfactory yields.
In the case of acetonitrile (runs 13 and 14), we failed
to selectively synthesize products 2h-4h. The synthesis
in the two-phase system consisting of chloroform or
benzene (runs 15-17) also holds little promise for the
selective preparation of bromo ketones even with the
use of the acid catalyst TsOH (run 16).
Taking into account the reaction conditions optimized
for the preparation of dibromoacetophenone 4h, we
synthesized dibromo ketones 4a-l from oximes 1a-l
(Table 2).
The above-described method for the synthesis
of dibromo ketones from oximes proved to be quite
general and gives products in preparative yields.
3. Results and discussion
The present study consists of two parts. First, we
examined the influence of the reaction factors on the
yields of the products 2h-5h by an example of the model
compound, p-bromoacetophenone oxime 1h. Second,
we performed the preparative synthesis of dibromo
ketones 4a-l from oximes 1a-l taking into account the
optimized conditions.
In the first part of the study, the reaction of
p-bromoacetophenone oxime 1h with H2O2aq-HBraq
system was performed in single- and two-phase
systems with the use of the following solvents: acetic
acid, dioxane, acetonitrile, chloroform, and benzene.
A36%aqueousH2O2 solutionwasaddedtoasuspension
or solution of oxime 1h followed by the addition of a 48%
aqueous HBr solution with stirring and cooling. Then
the reaction mixture was heated to the boiling point
and refluxed during a preset period of time. Depending
363

Synthesis of dibromo ketones by the reaction
of the environmentally benign H2O2-HBr system with oximes
Table 1. Influence of the reaction conditions on the results of the reaction of oxime 1h with the H2O2aq-HBraq systema.
O
NOH
O
O
O
Br
Br
Br
+
Br
H2O2aq - HBraq
Br
+
+
Br
Br
Br
Br
Br
Br
1h
2h
3h
5h
4h
Run
Mol H2O2/ mol
1h
Mol HBr/ mol
1h
Solvent
Reaction time
(min)
Yield, %
2h
3h
4h
5h
1
2
3
4
5
6
7
8
0.5
1.5
1.5
2
5
3
5
5
4
5
10
0
5
3
4
5
3
5
5
5
5
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
dioxane
dioxane
dioxane
MeCN
MeCN
CHCl3
CHCl3
PhH
20
20
32
27
13
2.3
-
62
67
73
62
-
3
3
9
-
-
20
-
40
31
68
87
77
-
-
2.5
2.5
2.5
2.5
0
90
16
9
-
20
-
-
20
-
16
-
20
80
24
49
11
-
-
b
9
120
20
66
46
73
18
47
46
13
59
65
4
-
10
11
12
13
14
15
16
17
1.5
2
-
-
20
5
-
2.5
1.5
2.5
2.5
2.5c
2.5
30
69
-
-
20
50
-
-
60
53
2
1
-
210
210
60
71
11
3
18
26
-
2
a General procedure: a 36% aqueous H2O solution (44-221 mg, 0.47-2.34 mmol) (except run 9) and a 48% aqueous HBr solution (0.47-1.57g,
2.8-9.34 mmol) (except run 8) were added2with stirring and water-bath cooling (15-20°C) to a solution of p-bromoacetophenone oxime 1h (200 mg,
0.934 mmol) in the solvent (2 mL), and the reaction mixture was refluxed.
b The total volume of acetic acid was 4 mL; air was bubbled through the reaction mixture.
c TsOH (53.3 mg, 0.28 mmol, 0.3mol / mol 1h) was added to the reaction mixture.
and bromine, into the ring (oximes 1g-i, runs 7-9) does
C4H9
O
C4H9
NOH
not interfere with the synthesis of dibromo ketones 4g-i
in good yields. The presence of the strong electron-
withdrawing nitro group in the nucleus of acetophenone
oxime (runs 10-11) leads to a decrease in the yield of
target dibromoacetophenones 4j (59%) and 4k (44%).
Aliphatic ketone oxime 1l is selectively transformed into
dibrominated product 4l (87% yield).
It is interesting to note that in the reaction of
undecan-6-one containing two methylene groups in
the α- and α’-positions relatively to the carbonyl group
with H2O2-HBr system bromination occurs of both these
positions. α-,α’–Dibromoketone 7 is prepared in 76%
yield, formation of α,α–dibromoketone is not observed
(Scheme 3).
Br
Br
H2O2aq - HBraq
dioxane
C4H9
C4H9
6
7
Scheme 3. Bromination of oxime 6 in the reaction with the H2O2-
HBr system.
Dibromoacetophenones 4a-d containing no functional
groups were synthesized in good yield (66-83%)
in runs 1-4. The bromination of methoxy- (1e) and
hydroxyacetophenone (1f) oximes (runs 5 and 6,
respectively) resulted in the bromination not only of the
side chain but also of the aryl ring. Noteworthy is the
high yield of product 4e (94%), whose synthesis involves
the following three reactions: deoximation, bromination
of the side chain, and bromination of the ring, each
reaction occurring in quantitative yield. The introduction
of electron-withdrawing substituents, such as chlorine
4. Conclusions
To sum up, we developed an easy-to-perform,
environmentally friendly and facile method for the
synthesis of dibromo ketones in yields varying from 40
364

A. O. Terent’ev et al.
Table 2. Synthesis of dibromo ketones 4a-l by the reaction of oximes 1a-l with the H2O2aq-HBraq systema.
O
NOH
Br
Br
H2O2aq - HBraq
R'
R'
R''
R''
1a-l
4a-l
Run
Oxime 1
Mol H2O2 / mol 1 Mol HBr / mol 1
Dibromo ketone 4, yield %
NOH
O
Br
1
3
4
6
Br
1a
1b
4a, 66 (68)b
OH
O
N
Br
2c
10
Br
4b, 83
OH
O
N
Br
3
4
10
Br
4c, 72
1c
1d
NOH
O
Br
4
5
3
6
Br
4d, 74
NOH
O
Br
Br
4.5
10
Br
O
O
1e
4e, 94
O
NOH
Br
Br
6
4.5
10
Br
HO
HO
Br
4f, 40
1f
NOH
NOH
O
Br
7
8
3
6
5
Br
Cl
Br
Cl
1g
1h
4g, 75 (73)b
O
Br
2.5
Br
Br
4h, 84
365

Synthesis of dibromo ketones by the reaction
of the environmentally benign H2O2-HBr system with oximes
ContinuedTable 2. Synthesis of dibromo ketones 4a-l by the reaction of oximes 1a-l with the H2O2aq-HBraq systema.
O
NOH
Br
Br
H2O2aq - HBraq
R'
R'
R''
R''
1a-l
4a-l
Run
Oxime 1
Mol H2O2 / mol 1 Mol HBr / mol 1
Dibromo ketone 4, yield %
NOH
O
Br
Br
Br
9
3
8
Br
1i
1j
4i, 75
NOH
NOH
O
O
O2N
Br
O2N
10
4.5
11
Br
4j, 59
Br
11
12
5
4
10
Br
O2N
O2N
1k
4k, 44
O
NOH
Br
8
Br
1l
4l, 87
a General procedure: a 36% aqueous H2O2 solution (2.34-6.95 mmol; 2.5-5 mol H2O2 per mole of 1a-l) and a 48% aqueous HBr solution (4.67-13.9 mmol;
6-11 mol HBr per mole of 1a-l) were added with stirring and water-bath cooling (15-20°C) to a solution of oxime 1a-l (200 mg, 0.934-1.74 mmol) in AcOH
(2-4mL), and the reaction mixture was refluxed (89-106°C) for 20 min.
b The synthesis was scaled up by a factor of 10.
c Dioxane as the solvent.
to 94% based on the reactions of oximes with the H2O2aq- Acknowledgments
HBraq system. The results of the present study extend
the potential of the use of oximes for the protection of This work is supported by the Program for Support of
the carbonyl group, which offers the ability to perform not Leading Scientific Schools of the Russian Federation
only conventional deoximation but also the subsequent (Grant NSh 4659.2012.3), the Grant of the Russian
in situ bromination of the resulting ketones. The process Foundation for Basic Research (Grant 11-03-00857-a),
can be scaled up and dibromo ketones can be prepared and the Ministry of education and science of the Russian
in gram amounts.
Federation (Grant 16.513.11.3108).
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