Selective aerobic oxidative dibromination of alkenes with aqueous HBr and sodium nitrite as a catalyst

Article abstract of DOI:10.1039/b814989e

Various alkenes (internal, terminal, aryl and alkyl substituted) and 1,2-diphenylethyne were efficiently and selectively dibrominated using 2 equivalents of 48% aqueous hydrobromic acid, with air as an oxidant and sodium nitrite as a catalyst. Despite the presence of water, only trans dibromination occurred producing anti-1,2-dibromoalkanes and (E)-1,2-dibromo-1,2- diphenylethene. A comparison of resource demand, waste production and environmental, health and safety issues of the NaNO₂ catalyzed aerobic bromination with molecular bromine and other oxidative bromination methods revealed that the proposed method is not only selective and effective but has a better environmental profile.

Full text of DOI:10.1039/b814989e

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Selective aerobic oxidative dibromination of alkenes with aqueous HBr and
sodium nitrite as a catalyst†
Ajda Podgorsˇek,a Marco Eissen,b Jens Fleckenstein,b Stojan Stavber,a Marko Zupana,c and Jernej Iskra*a
Received 28th August 2008, Accepted 15th October 2008
First published as an Advance Article on the web 17th November 2008
DOI: 10.1039/b814989e
Various alkenes (internal, terminal, aryl and alkyl substituted) and 1,2-diphenylethyne were
efficiently and selectively dibrominated using 2 equivalents of 48% aqueous hydrobromic acid,
with air as an oxidant and sodium nitrite as a catalyst. Despite the presence of water, only trans
dibromination occurred producing anti-1,2-dibromoalkanes and (E)-1,2-dibromo-1,2-
diphenylethene. A comparison of resource demand, waste production and environmental, health
and safety issues of the NaNO2 catalyzed aerobic bromination with molecular bromine and other
oxidative bromination methods revealed that the proposed method is not only selective and
effective but has a better environmental profile.
a more suitable solvent could be a promising way of overcoming
Introduction
the current drawbacks, especially when either hydrogen peroxide
Bromination of alkenes and alkynes has garnered a signifi-
or oxygen, as the most environmentally benign of the oxidants,
cant amount of attention among those studying bromination
are involved.7–10
reactions. Dibrominated derivatives are useful precursors for
Alkenes are useful substrates for investigating the nature
organometallic reagents and are widely applicable as interme-
of active halogenating agents11 and are used many times
diates in synthetic organic chemistry.1,2 However, the use of
in biomimetic studies of haloperoxidation, mainly with a
molecular bromine in chlorinated solvents remains the preferred
metal catalyst.12 Research has focused on the selectivity of
choice in the dibromination of organic molecules in spite of
bromohydrin and dibromide formation in a vanadium(V) or
its toxic and corrosive nature. Moreover, the reactive nature
molybdenium(VI) catalyzed oxybromination of alkenes using
of bromine results in highly exothermic reactions that makes
potassium bromide and hydrogen peroxide. Performing these
performing bromination in a selective manner difficult and leads
reactions in water gave bromohydrin as the main product,
to its substitution by different pyridinium and quarternary am-
despite a large excess of bromide ions.13 In a two-phase sys-
monium tribromides3 or N-bromosuccinimide in combination
9d,12c,d,13
tem using either H2O-CHCl3
or H2O-CH2Cl2,12d,e more
with lithium bromide.4 The negative impact of such brominating
protocols on the environment includes the use of environmen-
tally unfriendly solvents, significant waste production and the
need to remove residual reagents.5 Nevertheless, bromine is
still needed to prepare the reagents and when compared to
alternative protocols, this classical approach of using molecular
bromine remains resource efficient.5b Alternatively, nature has
developed a molecular halogen-free strategy for halogenation
using hydrogen peroxide (haloperoxidase) or oxygen (flavin
dependent halogenase) and X- to produce “X+” at the enzyme’s
active site.6 The oxidative halogenation with the in situ formation
of an active brominating species via the oxidation of bromide in
dibrominated product together with bromohydrin was formed.
Only when tetrabutylammonium bromide together with H2O2
and catalytic V2O5 in H2O-CH3CN was used as a tribromide
precursor was the formation of dibromides from cyclohexene
and styrene observed.9c A non-catalyzed oxidative bromination
with H2O2/HBr in a two-phase system with either CCl4 or an
ionic liquid also gave dibromides selectively.8a,14
In contrast with hydrogen peroxide, oxygen has seldom
been used for oxidative halogenation despite it being the most
abundant, cheapest and atom economical oxidant. Only a few
examples of aerobic oxybrominations of aromatic compounds
catalyzed by various metal catalysts are reported.10b,f,g Zhang
et al. describe a metal-free catalyzed oxidative bromination of
aromatic compounds and aryl ketones utilizing a combination
of aqueous hydrobromic acid, molecular oxygen and sodium
nitrite as the catalyst.10c A similar system was also used for
aerobic iodination.10d To the best of our knowledge, there
are only two examples of aerobic oxidative halogenation that
includes the oxidative halogenation of alkenes using a metal
species as a catalyst. Bromination of 1-octene10g and chlorination
of cyclododecene and trans-5-decene15 resulted in the non-
stereoselective formation of dihaloalkanes accompanied by
products of addition of hydrohalic acid to the double bond.
aLaboratory of Organic and Bioorganic Chemistry, “Jozˇef Stefan”
Institute, Jamova 39, 1000, Ljubljana, Slovenia.
E-mail: jernej.iskra@ijs.si; Fax: +386 1 4773 822; Tel: +386 1 4773 631
bGymnasium Ganderkesee, Am Steinacker 12, 27777, Ganderkesee,
Germany
cFaculty of Chemistry and Chemical Technology, University of Ljubljana,
Asˇkercˇeva 5, 1000, Ljubljana, Slovenia
† Electronic supplementary information (ESI) available: NMR spectra
of (2,3-dibromo-1,1,1-trifluoropropan-2-yl)benzene 20, Environmental
factor E of different bromination methods, UV-vis spectra of Br2 in
CH3CN and UV-vis spectra of NOBr. See DOI: 10.1039/b814989e
120 | Green Chem., 2009, 11, 120–126
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Table 1 The effect of the mode of addition of NaNO2 on aerobic
oxidative bromination of styrene (1) with hydrobromic acid
This report presents a study on the selective and stereoselective
aerobic dibromination of alkenes and alkynes using air at near
ambient pressure as the oxidant, an equimolar amount of
aqueous hydrogen bromide and sodium nitrite as a catalyst.
Environmental aspects, such as resource demands and waste
production together with health and safety issues, will be
evaluated in comparison to Br2 addition and other oxidative
bromination. Furthermore, the effect of the slow generation of
the “active brominating agent” on the selectivity of bromination
is discussed.
Distribution (%)b
Entry Methoda
1
:
2
:
3
:
4
1
2
3
4
5
A
B
C
/
/
/
:
:
:
:
:
94
95
98
/
:
:
:
:
:
6
5
2
/
/
:
:
:
:
:
/
/
/
34
48
C, without addition of NaNO2 66
C, without an air balloon 18
Results and discussion
34
To define optimum reaction conditions for oxidative bromina-
tion of alkenes in an HBr/air/NaNO2(cat.) system we initially
studied the reaction of styrene (1) in different solvents (ace-
tonitrile, ethyl acetate, dichloromethane, hexane, methanol and
water). Styrene (1) makes an excellent test substrate since its
transformation is particularly sensitive to reaction conditions,
eg. polymerization, incorporation of various nucleophiles from
the milieu into the first-formed carbocation. First, 1 mmol of
styrene (1) was dissolved in 10 mL of MeCN, then 2 mmol
of 48% aqueous HBr (226 mL) and 5 mol% of NaNO2 were
added. The flask was immediately covered with an air filled
balloon and stirred at 22 ◦C for 5 hours. On completion,
ethyl acetate was added. The organic phase was discoloured
by adding a few drops of 37% aq. NaHSO3, neutralized by
NaHCO3 and dried over anhydrous Na2SO4. After removing
the solvent, the 1,2-dibromo-1-phenylethane (2) was obtained.
The role of solvent on functionalization of 1 is shown on
Scheme 1. The best yield of 2 is obtained in acetonitrile,
where only a trace amount of bromohydrin 3 was observed in
the crude reaction product. Also, no excess hydrogen bromide
was necessary for the complete conversion of styrene (1) into
dibromide 2. Interestingly, although 10 equivalents of water were
present in the reaction mixture from using an aqueous solution
of HBr, it did not interfere in the bromination process by forming
bromohydrin 3. In ethyl acetate, 78% of the dibrominated
product 2 was formed non-selectively, the reaction in hexane gave
a complex mixture of products, while in dichloromethane only
a trace amount of 2 was obtained. Moreover, the use of either
methanol or water as a reaction medium completely suppressed
the oxidative bromination of styrene (1).
a Method A: 5 mol% of solid NaNO2 was added in a single portion,
Method B: 5 mol% of solid NaNO2 was added in three portions every
2 hours, Method C: 20 mL of 2.5 M aq. NaNO2 was added; b Determined
by 1H NMR spectroscopy.
2 hours (Method B) and as a 20 mL aqueous solution of 2.5 M
NaNO2 (Method C). Table 1 shows that there is no significant
difference when sodium nitrite is added either all at once or
in three discrete portions. However, a slightly higher yield of
dibrominated product 2 was obtained when sodium nitrite was
added as a 2.5 M aqueous solution, possibly because the sodium
nitrite was uniformly distributed in the reaction mixture. Inter-
estingly, although additional water was present in the system
less bromohydrin was formed. Therefore, in all subsequent
experiments an aqueous solution of sodium nitrite was added.
To highlight the role of sodium nitrite and the presence
of air on the course of oxidative bromination of styrene (1),
blank experiments both without sodium nitrite and air were
performed. In the absence of sodium nitrite, the addition of HBr
to styrene (1) is the sole reaction with 34% of (1-bromo-ethyl)-
benzene (4) being formed (Table 1). In the absence of air only
34% of the dibrominated product 2 was formed and the addition
of HBr on the double bond was the main reaction resulting in the
formation of 4 in a 48% yield. From this we can conclude that
catalytic amounts of sodium nitrite under aerobic conditions
prevent the addition of hydrobromic acid to the alkene, while air
as an oxidant enables the “in situ” formation of the brominating
species and therefore the dibromination of the alkene.
To evaluate the scope of this catalytic system, optimum reac-
tion conditions: 1 mmol of substrate, 2 mmol of 48% aqueous
solution of HBr, 20 mL of 2.5 M aq. NaNO2 (5 mol%) and
10 mL of acetonitrile, were used to oxidatively brominate various
internal and terminal aryl and alkyl substituted alkenes and
1,2-diphenylethyne. The results are represented in Schemes 2–5.
Yields were determined by 1H NMR spectroscopy and are based
on the starting compound, while the yields given in parentheses
refer to isolated yields. Using this method, b-substituted styrenes
were quantitatively and diastereoselectively converted to di-
brominated products (Scheme 2). Bromination of trans-stilbene
(8), ethyl trans-cinnamate (9) and acenaphthylene (11) gave
anti-brominated products diastereo-specifically. cis-Stilbene (5)
was also trans brominated under the above conditions yielding
syn-1,2-dibromo-1,2-diphenylethane (6) accompanied by 5% of
the anti isomer 7.
Scheme 1
Next, the effect of the mode of addition of sodium nitrite
on conversion was investigated. Five mol% of solid NaNO2
was added in one portion (Method A), in three portions every
The introduction of a second substituent in the a posi-
tion in styrene (1) modifies the stability of the carbocation
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In a small scale experiment, extraction or dilution with an
appropriate organic solvent has to be applied in a work-up
procedure. This method has the potential of producing a simpler
work-up procedure due to the absence of any organic by-
products and residues. On a larger scale, 5-times less MeCN
is required for the reaction and a different work-up procedure,
depending on the aggregate state of the formed product, was
employed. Oxidative bromination of trans-stilbene (8) and trans-
4-octene (23) were performed on a 5 mmol scale (5 mmol of
alkene, 10 mmol of 48% aq. HBr, 70 mL of 3.6 M aq. NaNO2,
10 mL of CH3CN). After stirring the reaction mixture for either
16 h or 24 h at room temperature, the acetonitrile was distilled
off and regenerated. In the case of the solid product 7, the crude
reaction mixture was poured into water and the resultant white
precipitate was filtered off, and after drying 95% of meso-1,2-
dibromo-1,2-diphenylethane (7) was obtained. In the case of the
liquid product 24, a minimum quantity of EtOAc was added, the
resultant organic phase was dried over Na2SO4 and the solvent
was evaporated. The result was anti-4,5-dibromooctane (24) in
a 94% yield.
When comparing alternative protocols, the relevant envi-
ronmental, health and safety aspects must also be taken into
consideration. Regarding resource efficiency, the conventional
procedure using molecular bromine16 (Scheme 6a) or hydro-
bromic acid and hydrogen peroxide8a (Scheme 6b) compare
favourably to the twenty-four procedures examined.5b These
procedures had been chosen to be juxtaposed to the larger-scale
procedure for aerobic oxidative dibromination of trans-stilbene
(8) with HBr/air/NaNO2(cat.) system (Scheme 6c).
Scheme 2
intermediate so that besides the competitive addition of a
nucleophile, deprotonation resulting in an addition–elimination
process could become an important reaction channel. With a-
methylstyrene (13), only an addition reaction occurred with the
competitive formation of the dibromide 14 and the bromohydrin
15 in a ratio of 44/56. (Scheme 3). a-(Trifluoromethyl)styrene
(16), that forms a more deactivated bromocarbonium ion, was
brominated in a lower yield, nevertheless dibromoalkane 17
was the main product. Bromination of 1,1-diphenylethene (18)
follows an addition-elimination mechanism to give 2-bromo-
1,1-diphenylethene (20) and 35% of the addition product 19.
Scheme 3
The aliphatic terminal alkene 21 and internal alkene 23
were quantitatively and selectively brominated to give 1,2-
dibromooctane (22) and anti-4,5-dibromooctane (24), respec-
tively (Scheme 4).
Scheme
6
Bromination methods using (a) molecular bromine,16
(b) hydrobromic acid and hydrogen peroxide,8a and (c) hydrobromic
acid and oxygen.
The protocols are from the laboratory stage. Against
ꢀ
Scheme 4
this background, the environmental factors E =
Waste
[kg]/Product [kg] given in Fig. 1 demonstrate that there is no
significant difference regarding waste production and solvent
demand between this method and other bromination methods5b
with much higher E factors. Protocol (a) has the advantage that
no water is used so waste water treatment is unnecessary.
On completion, aerobic oxidative bromination was tested
for bromination of the alkyne 25. Similarly to reactions with
alkenes, 25 was also trans-brominated to (E)-1,2-dibromo-1,2-
diphenylethene (26) stereospecifically with an isolated yield of
93% (Scheme 5).
Contrary to the quantitative results, the nature of the reagents
used distinguishes themselves notably. Both, molecular bromine
and an aqueous solution of hydrobromic acid have corrosive
properties. Additionally, hydrogen peroxide is not only corrosive
but can decompose in a runaway scenario.18 However, bromine
is much more volatile and has a higher risk potential than
hydrobromic acid. Another important issue is the use of toxic
Scheme 5
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Table 2 Break down of environmental factor E shown in Fig. 1
Table 3 Bromination of styrene (1) with various brominating reagents
(a)
(b)
(c)
Coupled products
By-products
Substrates (excess)
Catalysts
Impurities
Solvents
0.1119
0.0112
0.1066
0.057
0.0556
0.0526
0.0115
Distribution (%)a
0.0042
4.1054
2.5002
1.0478
3.7777
5.2359
0.6305
5.9905
Entry Reagent
Time (h) 2 : 3 : 27 : 28
Sewage/Water
Sum
4.1622
1
2
3
4
5
6
7
HBr (2eq.), NaNO2 (0.05 eq.), air
5
3
3
24
3
3
98 :
60 :
2
/
:
/
: /
Br2 (1eq.)b,c
: 20 : 20
Br2 (1eq.), H2O (10 eq.)b
Br2 (1eq.)d
61 : 23 : 11 : 5
96 :
98 :
84 : 14 :
90 : 10 :
4
2
:
:
/
/
1
/
: /
: /
: 1
HBr3 (1eq.)e
BrOH/NaBr (1eq.), H2O (10 eq.)f
H2O2 (1eq.), HBr (2 eq.)g
24
: /
a Determined by 1H NMR spectroscopy. b Styrene (1 mmol) was added
to the solution of Br2 (1 mmol) (and H2O (10 mmol)) in CH3CN (10 mL).
c A similar reactivity was observed to that reported in ref. 19. d Bromine
vapours were added by diffusion from the gaseous phase20 to the solution
of styrene (1 mmol) in CH3CN (10 mL). e Br2 (1 mmol) and HBr (1 mmol)
were mixed together in CH3CN (10 mL) followed by the addition of
styrene (1 mmol). f Br2 (1 mmol) and NaOH (1 mmol) were mixed
together and then the solution of styrene (1 mmol) in CH3CN (10 mL)
and H2O (10 mmol) was added. g 30% aq. H2O2 (1 mmol) and 48% aq.
HBr (2 mmol) were added to the solution of styrene (1 mmol) in CH3CN
(10 mL).
Fig. 1 Environmental factor E of different bromination methods
shown in Scheme 6 using the software EATOS.17 For details see Table 2.
Work-up procedures have not been described in detail8a,16 and, thus, were
not considered here: (a) recrystallization; (b) washing with water, brine
and drying over sodium sulfate; (c) pouring into 10 mL of water.
and environmentally problematic substances such as chloroform
(solvent of protocol (a)) or tetrachloromethane (solvent of
protocol (b)). Evidence, although limited, suggests that CCl4
is a carcinogen. Moreover it can have long-term adverse effects
on the aquatic environment, is ozone depleting and a greenhouse
gas. The authors of protocol (b) suggest dioxane as an alternative
solvent, but dioxane is an irritant, highly flammable, can form
explosive peroxides and potentially carcinogenic. Obviously, the
advantage of substituting bromine with hydrobromic acid in
protocol (b) becomes revoked because technology equipment
has to avert the potential risk associated with the use of
halogenated solvent or dioxane. In this regard, the application of
acetonitrile, albeit highly flammable but merely harmful instead
of toxic in protocol (c) respresents a significant progress and,
furthermore, air is used instead of hydrogen peroxide.
The actual mechanism of aerobic oxidative bromination using
hydrobromic acid and sodium nitrite as a catalyst is yet to
be investigated. However, bromine was proposed as a reactive
brominating species for the bromination of aromatic compounds
and aryl ketones.10c Alkenes are convenient substrates to study
the mechanism of halogenation and the nature of halogenating
reagents. We performed a study on the effect of a brominating
reagent’s structure and the mode of its addition on the course of
bromination of styrene (1) and observed some interesting results.
Classical bromination of 1 with bromine in acetonitrile follows
a different pathway to that of an HBr/air/NaNO2(cat.) system;
only 60% of 1,2-dibromo-1-phenylethane (2) was formed, with
the remainder being acetamide 27 and oxazole 28 formed by the
incorporation of acetonitrile into the carbocation intermediate
(Table 3, entry 2). An analogous reaction with an additional
10 equivalents of water, as is present when using aqueous HBr
in aerobic oxidative bromination, yielded a similar amount of
dibromide 2 (entry 3). Also, significant differences were notice-
able when molecular bromine was added slowly to a solution of
styrene (1) in acetonitrile by its diffusion via the gaseous phase.
In this case similar results to aerobic oxidative bromination
were obtained, with the selective formation of the dibrominated
product 2 (entry 4), thus pointing to the importance of the
slow formation of the brominating species during the course of
the oxidative bromination. A similar result was observed when
HBr3 was formed as a brominating agent prior to the addition
of 1; less bromohydrine 3 was formed despite aqueous HBr
being used (entry 5). When using BrOH/NaBr for bromination
(entry 6) and when the brominating agent is formed in situ via
haloperoxidase-like oxidation of HBr with hydrogen peroxide
(entry 7), the formation of bromohydrin 3 is more expressed. It
appears that the slow generation of bromine could be the key
for the selective formation of vic-dibromides with the possibility
of forming HBr3 due to an excess of HBr at the early stages of
the reaction.
Also, what is noteworthy is the selective formation of trans-
addition products in aerobic bromination. This result is different
to bromination with bromine in chlorinated solvents, where cis-
addition was also observed in the bromination of acenaphthy-
lene (11, trans : cis 70 : 30),21 trans-stilbene (8, trans : cis 84 : 16)22
and diphenylethyne (25, trans : cis 60 : 40).23 Alternatively,
when H2O2/HBr was used for bromination in a biphasic system
with CCl4 or an ionic liquid only trans-bromination takes place
in the bromination of methyl trans-cinnamate.8a,24 A similar
effect was observed in bromination with pyridinium tribromide,
where a reaction with trans-stilbene (8) in CH2Cl2 produces an
86 : 14 mixture of trans : cis-adducts, while the reaction in a
water suspension yields only the trans-adduct.22
Nitrogen oxides were suggested to be the catalyst in this
reaction due to a well known decomposition of nitrite under
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acidic conditions into a mixture of nitrogen oxides. By mixing
NaNO2 with a strong acid (HClO4) in MeCN, colorless bubbles
immediately start to evolve and solution remained colorless
even after a prolonged period of time in air. When HBr is
used as an acid, dark yellow bubbles appear and the solution
gradually becomes yellow-orange which, together with the fact
that a solution of bromine in MeCN is red-brown, suggests the
formation of a different decomposition product of NaNO2 with
HBr. A review of available literature suggests that the formation
of a nitrosyl bromide could explain the yellow-orange colour
of the solution (Scheme 7A). NOBr reportedly decomposes at
room temperature into nitric oxide and bromine (Scheme 7B).25a
We turned to UV-vis spectroscopy to determine the presence of
NOBr as a product of the decomposition of NaNO2 with HBr
in acetonitrile. In the spectra obtained for a solution of Br2 in
MeCN, two peaks at 269 (s) and 390 (br) nm are observed,
whereas for a degassed suspension of NaNO2 in MeCN treated
with HBr, a spectra is obtained with peaks at 269 (br) and
330 (br) nm. According to the literature data, NOBr has a
peak at 225 nm that is in our case overlapped by the strong
signal of Br2,25b,c while a broad band at 330 nm corresponds
with the literature one.25b However, after 30 min only absorption
signals for Br2 are observed. Our conclusion is that during
NaNO2 catalyzed aerobic dibromination of alkenes, nitrite is
first transformed into NOBr, which then decomposes to bromine
and nitric oxide (Scheme 7). Thus, a small amount of bromine
is already formed in this pre-catalytic phase and is rapidly
consumed by the alkene. This shifts the equilibrium towards
complete decomposition of NOBr.
Conclusion
Reported herein is a mild and simple method for the efficient
and selective bromination of alkenes, in which aqueous HBr is
used as a source of bromine, air at near ambient pressure as
the oxidant and NaNO2 as a low-cost catalyst. This procedure
performed in acetonitrile provides a practical alternative to
other procedures by avoiding the use of volatile bromine and
problematic halogenated solvents. Furthermore, the isolation
procedure is straightforward requiring only the separation of
the organic product from the inorganic salts. It was established
that NOBr is first formed from the catalyst and HBr and its
decomposition leads to the generation of NO that acts as the true
catalyst in aerobic oxidative bromination. In the bromination
step, the formation of different active brominating agents is
possible, however it seems that the selectivity of bromination
is governed by the slow formation of bromine through aerobic
oxidation, while its conversion into HBr3 with residual HBr
could also play an important role.
Both, environmental and health and safety aspects were also
considered and compared with alternative protocols and aerobic
dibromination. The obtained E-factors show that this aerobic
protocol is similar to bromination using Br2 and an H2O2/HBr
system in chlorinated solvents. However, aerobic bromination
with HBr/NaNO2/air replaces Br2 with the less volatile aqueous
HBr and hydrogen peroxide with air, while chlorinated solvents
are eliminated altogether. These and the good selectivity and
yield makes this method a promising alternative to other
dibromination protocols.
Experimental
General
All chemicals were obtained from commercial sources and were
used without further purification. Acetonitrile was distilled
before use. Column and thin layer chromatography were carried
out using silica gel 60 (0.063–0.200 mm) and silica 60F-245
Scheme 7
1
plates, respectively. H and 13C NMR spectra were recorded
At which point, nitric oxide enters into the catalytic cycle
of aerobic bromination, where it is oxidized into NO2 by air.
This in turn oxidizes HBr into Br2 (Scheme 8). It appears that
the slow generation of bromine is crucial for selective trans-
dibromination of alkenes, while the presence of unreacted HBr
in the reaction mixture makes the formation of HBr3 possible
and its role in selective dibromination can not be precluded
(Table 3, entries 4, 5).
in CDCl3 using a Varian Inova 300 MHz spectrometer. The
chemical shifts (d) are reported in ppm units relative to TMS as
1
an internal standard for H NMR and CDCl3 for 13C NMR
spectra. Melting points were determined using a Bu¨chi 535
melting point apparatus. Mass spectra were obtained using an
Autospec Q mass spectrometer with electron impact ionization
(EI, 70 eV).
Typical reaction procedure for aerobic oxidative dibromination
of alkenes and 1,2-diphenylethyne with HBr/air/
NaNO2(cat.) system
In a typical experiment 1.0 mmol of substrate was dissolved in
10 mL of freshly distilled acetonitrile, then 2.0 mmol of 48%
aqueous solution of HBr (226 mL) and 20 mL of 2.5 M aqueous
solution of NaNO2 (0.05 mol of NaNO2) were added. The flask
was immediately covered with an air filled balloon (1 L) and the
solution stirred at room temperature for 5–24 h. The progress of
the reaction was monitored by TLC. At the end of the reaction,
5 mL of ethylacetate was added. The organic phase was dis-
coloured by adding a few drops of 37% aq. NaHSO3, neutralized
Scheme 8
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by NaHCO3 and finally dried over anhydrous Na2SO4. After the
removal of solvent, the isolated reaction mixture was analyzed by
1H NMR spectroscopy. Finally, products were isolated by flash
or column chromatography (SiO2, hexane–EtOAc) or purified
by crystallization and their structures determined by comparison
with the literature data.
1-bromo-2-phenylpropan-2-ol (15),26 86 mg (40%). oil; dH
(300 MHz; CDCl3; Me4Si) 1.67 (s, 3H, CH3), 3.68 (d, J 10.4,
1H), 3.75 (d, J 10.4, 1H), 7.23–7.30 (m, 1H, Ar-H), 7.33–7.39
(m, 2H, Ar-H), 7.43-7.47 (m, 2H, Ar-H); dC (76 MHz; CDCl3;
Me4Si) 28.0 (CH3), 46.2 (CHBr), 73.1 (COH), 124.8 (Ar-C),
127.5 (Ar-C), 128.4 (Ar-C), 144.1 (Ar-C); m/z (EI, 70 eV) 198
(1%), 196 (1%), 121 (100%), 105 (15%), 77 (17%).
(1,2-Dibromoethyl)benzene (2),26 5 h at r.t., 237 mg (90%).
mp 70–72 ◦C (lit.27 73 ◦C), white crystals; dH (300 MHz; CDCl3;
Me4Si) 4.06 (t, J 10.4, 1H, CH2Br), 4.08 (dd, J 10.4, 5.7, 1H,
CH2Br), 5.14 (dd, J 10.4, 5.7, 1H, CHBr), 7.32–7.42 (m, 5H,
Ar-H); dC (76 MHz; CDCl3; Me4Si) 35.0 (CH2Br), 50.9 (CHBr),
127.6 (Ar-C), 128.8 (Ar-C), 129.2 (Ar-C), 138.6 (Ar-C); m/z (EI,
70 eV) 185 (60%), 183 (60%), 104 (100%).
(2,3-Dibromo-1,1,1-trifluoropropan-2-yl)benzene (17), 24 h at
r.t., 232 mg (70%). oil; dH (300 MHz; CDCl3; Me4Si) 4.18 (d, J
11.9, 1H, CH2Br), 4.38 (d, J 11.9, 1H, CH2Br), 7.39–7.45 (m, 3H,
Ar-H), 7.64–7.67 (m, 2H, Ar-H); dC (76 MHz; CDCl3; Me4Si)
34.9 (CH2Br), 65.7 (q, J 28.2, C), 123.6 (q, J 283, CF3), 128.4
(Ar-C), 128.9 (Ar-C), 129.7 (Ar-C), 133.0 (Ar-C); m/z (EI, 70
eV) 334 (M++4, 0.2%), 332 (M++2, 1%), 330 (M+, 0.2%), 253
(96%), 251 (96%), 172 (100%), 103 (65%), 77 (43%); Exact mass
calculated for C9H7F3Br2 329.886657, found 329.888000.
rac-1,2-Dibromo-1,2-diphenylethane (6◦),28 8 h at r.t., 306 mg
◦
(90%). mp 105–107 C (lit.28 112–113 C), white crystals; dH
(300 MHz; CDCl3; Me4Si) 5.48 (s, 2H, CHBr), 7.16 (s, 10H,
Ar-H); dC (76 MHz; CDCl3; Me4Si) 59.1 (CHBr), 128.1 (Ar-C),
128.5 (Ar-C), 137.8 (Ar-C); m/z (EI, 70 eV) 342 (0.3%, M++4),
340 (0.6%, M++2), 338 (0.3%, M+), 261 (47%), 259 (47%), 180
(100%), 171 (43%), 169 (43%).
(2-Bromoethene-1,1-diyl)dibenzene (20),33 24 h at r.t., 143 mg
◦
(55%). mp 48–50 C (lit.34 42–43 ◦C), white crystals; dH
(300 MHz; CDCl3; Me4Si) 6.76 (s, 1H, CHBr), 7.18–7.24 (m,
2H, Ar-H), 7.25–7.33 (m, 5H, Ar-H), 7.34–7.43 (m, 3H, Ar-H);
m/z (EI, 70 eV) 260 (M++2, 60%), 258 (M+, 60%), 179 (100%).
meso-1,2-Dibromo-1,2-diphenylethane (7),26 12 h at r.t., 323 mg
◦
◦
(95%). mp 249–250 C (lit.29 242–243 C), white crystals; dH
(300 MHz; CDCl3; Me4Si) 5.48 (s, 2H, CHBr), 7.34–7.45 (m, 6H,
Ar-H), 7.50–7.54 (m, 4H, Ar-H); dC (76 MHz; CDCl3; Me4Si)
56.1 (CHBr), 127.9 (Ar-C), 128.8 (Ar-C), 129.0 (Ar-C), 139.3
(Ar-C); m/z (EI, 70 eV) 342 (0.3%, M++4), 340 (0.6%, M++2),
338 (0.3%, M+), 261 (57%), 259 (57%), 180 (100%), 171 (12%),
169 (12%).
1,2-Dibromooctane (22),35 24 h at r.t., 250 mg (92%). oil; dH
(300 MHz; CDCl3; Me4Si) 0.87–0.92 (m, 3H, CH3), 1.23–1.62
(m, 8H, (CH2)4), 1.72–1.84 (m, 1H, CH2), 2.08–2.19 (m, 1H,
CH2), 3.63 (t, J 10.0, 1H, CH2Br), 3.85 (dd, J 10.2, 4.4, 1H,
CH2Br), 4.13–4.21 (m, 1H, CHBr); dC (76 MHz; CDCl3; Me4Si)
14.0, 22.5, 26.7, 28.5, 31.6, 36.0, 36.3, 53.1; m/z (EI, 70 eV) 193
(6.5%), 191 (6.5%), 151 ( 6%), 149 (7.3%), 137 (4.5%), 135 (6%),
121 ( 2%), 119 (3.7%), 111 (70%), 69 (100%).
anti-Ethyl 2,3-dibromo-3◦-phenylpropanoate (10),30 24 h at r.t.,
312 mg (93%). mp 66–67 C (lit.30 71–72 ◦C), white crystals; dH
(300 MHz; CDCl3; Me4Si) 1.38 (t, J 7.1, 3H, CH3), 4.36 (q, J 7.1,
2H, CH2), 4.83 (d, J 11.8, 1H, CHBr(COOEt)), 5.34 (d, J 11.8,
1H, CHBr(Ph)), 7.33–7.42 (m, 5H, Ar-H); dC (76 MHz; CDCl3;
Me4Si) 13.9 (CH3), 47.0 (CHBr(Ph)), 50.7 (CHBr(COOEt)),
62.6 (CH2), 128.0 (Ar-C), 128.9 (Ar-C), 129.3 (Ar-C), 137.6
(Ar-C), 167.8 (Ar-C); m/z (EI, 70 eV) 338 (0.5%, M++4), 336
(1.1%, M++2), 334 (0.5%, M+), 293 (1%), 291 (2.5%), 289 (1%),
265 (1.7%), 263 (3.2%), 261 (1.7%), 257 (65%), 255 (65%), 185
(30%), 183 (30%), 131 (65%), 103 (100%), 91 (25%), 77 (55%).
anti-4,5-Dibromooctane (24),35 24 h at r.t., 252 mg (92%). oil;
dH (300 MHz; CDCl3; Me4Si) 0.95 (t, J 7.4, 6H, CH3), 1.37–1.53
(m, 2H, CH2), 1.58–1.74 (m, 2H, CH2), 1.86–2.12 (m, 4H, CH2),
4.13–4.21 (m, 2H, CHBr); dC (76 MHz; CDCl3; Me4Si) 13.4
(CH3), 20.3 (CH2), 38.9 (CH2), 59.8 (CHBr); m/z (EI, 70 eV)
193 (4%), 191 (4%), 111 (46%), 69 (100%).
(E)-1,2-Dibromo-1,2-diphenylethane (26),36 24 h at r.t., 314 mg
◦
◦
(93%). mp 214–215 C (lit.36 215–216 C), white crystals; dH
(300 MHz; CDCl3; Me4Si) 7.34–7.46 (m, 6H, Ar-H), 7.51–7.55
(m, 4H, Ar-H); m/z (EI, 70 eV) 340 (M++4, 15%), 338 (M++2,
30%), 336 (M+, 15%), 259 (12%), 257 (12%), 178 (100%).
trans-1,2-Dibromo-1,2-dihydroacenaphthylene (12),31 8 h at
◦
r.t., 300 mg (96%). mp 122 C (lit.32 121–122 ◦C), brown
crystals; dH (300 MHz; CDCl3; Me4Si) 6.00 (s, 2H, CHBr), 7.58–
7.64 (m, 4H, Ar-H), 7.78–7.84 (m, 2H, Ar-H); dC (76 MHz;
CDCl3; Me4Si) 54.9 (CHBr), 122.5 (Ar-C), 125.8 (Ar-C), 128.8
(Ar-C), 130.9 (Ar-C), 134.8 (Ar-C), 140.5 (Ar-C); m/z (EI, 70
eV) 314 (1%, M++4), 312 (3%, M++2), 310 (1%, M+), 233 (23%),
231 (23%), 152 (100%).
Larger-scale procedure for aerobic oxidative dibromination of
trans-stilbene (8) with HBr/air/NaNO2(cat.) system
5.0 mmol (901 mg) of 8 was mixed with 10 mL of freshly distilled
acetonitrile, then 10.0 mmol of a 48% aqueous solution of HBr
(1.13 mL) and 70 mL of a 3.6 M aqueous solution of NaNO2
(0.25 mol of NaNO2) were added. The flask was immediately
covered with an air filled balloon (1 L) and solution stirred at
room temperature for 12 hours. The progress of the reaction
was monitored by TLC. At the end of the reaction MeCN was
evaporated under reduced pressure, crude reaction mixture was
poured into 10 mL of water and white precipitate was filtered
off. After drying, 1.615 g (4.75 mmol) of 7 was obtained as white
crystaline product.
(1,2-Dibromopropan-2-yl)benzene (14),26 24 h at r.t., 97 mg
(35%). oil; dH (300 MHz; CDCl3; Me4Si) 2.32 (s, 3H, CH3),
4.13 (d, J 10.2, 1H, CHBr), 4.35 (d, J 10.2, 1H, CHBr), 7.28–7.40
(m, 3H, Ar-H), 7.53-7.57 (m, 2H, Ar-H). dC (76 MHz; CDCl3;
Me4Si) 29.9 (CH3), 40.8 (CHBr), 43.5 (CBr), 126.5 (Ar-C), 128.5
(Ar-C), 128.6 (Ar-C), 141.8 (Ar-C); m/z (EI, 70 eV) 198 (34%),
196 (34%), 117 (100%) and
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Larger-scale procedure for aerobic oxidative dibromination of
trans-4-octene (23) with HBr/air/NaNO2(cat.) system
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5.0 mmol (561 mg) of 23 was mixed with 10 mL of freshly distilled
acetonitrile, then 10.0 mmol of a 48% aqueous solution of HBr
(1.13 mL) and 70 mL of a 3.6 M aqueous solution of NaNO2
(0.25 mol of NaNO2) were added. The flask was immediately
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room temperature for 24 hours. The progress of the reaction
was monitored by TLC. At the end of the reaction MeCN
was evaporated under reduced pressure. Crude reaction mixture
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and inorganic material filtered off. After evaporating the solvent
1.278 g (4.70 mmol) of 24 was obtained as oily product.
Acknowledgements
This research has been supported by the Ministry of Higher
Education, Science and Technology of the Republic of Slovenia
and the Young Researcher Program (A.P.) of the Republic of
Slovenia. The authors are grateful to the staff of the National
NMR Centre at the National Institute of Chemistry in Ljubljana
and the staff of the Mass Spectroscopy Centre at the JSI. We are
grateful to Prof. Dieter Lenoir for helpful discussions.
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