TsNBr2mediated oxidative functionalization of alkynes

Article abstract of DOI:10.1016/j.tet.2016.05.017

A new approach has been developed for oxidative transformation of alkynes by controlled manipulation of TsNBr₂mediated process. Alkynes could be readily converted to ketones and α-bromoketones via an oxybromination–debromination sequence. When alkynes are treated successively with TsNBr₂, KI and Na₂SO₃in a mixture of acetone and water at room temperature, corresponding ketones were obtained. On the other hand, treatment of alkynes with TsNBr₂and Na₂SO₃in a mixture of ethyl acetate, acetone and water at room temperature could produce corresponding α-bromoketones. 1-Bromoalkynes could also be synthesized from corresponding alkynes within a very short time using TsNBr₂at room temperature. In all cases, excellent yields of corresponding products are obtained.

Full text of DOI:10.1016/j.tet.2016.05.017

Accepted Manuscript
TsNBr mediated oxidative functionalization of alkynes
2
Kamal Krishna Rajbongshi, Debojit Hazarika, Prodeep Phukan
PII:
S0040-4020(16)30390-8
10.1016/j.tet.2016.05.017
TET 27744
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 October 2015
Revised Date: 23 February 2016
Accepted Date: 6 May 2016
Please cite this article as: Rajbongshi KK, Hazarika D, Phukan P, TsNBr mediated oxidative
2
functionalization of alkynes, Tetrahedron (2016), doi: 10.1016/j.tet.2016.05.017.
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ACCEPTED MANUSCRIPT
Leave this area blank for abstract info.
TsNBr2 mediated oxidative functionalization of alkynes
Kamal Krishna Rajbongshi, Debojit Hazarika and Prodeep Phukan
R
Br
CH2Cl2 (3 mL)
rt
DBU,
O
O
Na2SO3,
KI, Na2SO3,
Br
R
R
R
Ethyl Acetate (1mL)
Acetone:H2O (0.1mL)
rt
Acetone/H2O (3.1 mL)
rt
+
TsNBr2
1

ACCEPTED MANUSCRIPT
TsNBr2 mediated oxidative functionalization of alkynes
Kamal Krishna Rajbongshi, Debojit Hazarika and Prodeep Phukan*
Department of Chemistry, Gauhati University, Guwahati -781014, Assam, India;
E-mail: pphukan@yahoo.com
Abstract: A new approach has been developed for oxidative transformation of alkynes by
controlled manipulation of TsNBr2 mediated process. Alkynes could be readily converted to
ketones and α-bromoketones via an oxybromination - debromination sequence. When alkynes
are treated successively with TsNBr2, KI and Na2SO3 in a mixture of acetone and water at room
temperature, corresponding ketones were obtained. On the other hand, treatment of alkynes with
TsNBr2 and Na2SO3 in a mixture of ethyl acetate, acetone and water at room temperature could
produce corresponding α-bromoketones. 1-Bromoalkynes could also be synthesized from
corresponding alkynes within a very short time using TsNBr2 at room temperature. In all cases,
excellent yields of corresponding products are obtained.
Key words: TsNBr2; Alkyne; Ketone; α-Bromoketone; 1-Bromoalkyne
1. Introduction
Activation and functionalization of the carbon-carbon triple bond is a fundamental process in
organic synthesis as it facilitates installation of a variety of important functional groups.1 A range
of organic synthons such as ketones, α-bromoketones, bromoalkynes can be synthesized from
alkynes, particularly with the aid of transition metal catalyst.1 Although functionalization of
olefin has been studied extensively, conversion of alkyne to other functionality is yet to be
explored to the fullest extent. Use of transition metal catalyst is a common strategy for activation
2

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of C-C triple bond. However, the use of expensive and toxic metals limits the application of such
protocols to a greater extent. In this context, the development of a transition metal-free protocol
is a superior alternative for various synthetic manipulations. We have recently established that N,
N-dibromo-p-toluenesulfonamide (TsNBr2) is a highly reactive reagent for diverse organic
transformations without using any catalyst.2 In continuation of our work on this particular
reagent, we are reporting herein some important transformations of alkynes using TsNBr2
(Scheme1).
Na2SO3,
KI, Na2SO3,
O
O
R
Br
Ethyl Acetate (1mL)
Acetone:H2O (0.1mL)
rt
R
Acetone/H2O (3.1 mL)
rt
+
R
TsNBr2
DBU,
CH2Cl2(3 mL)
rt
R
Br
Scheme 1: Functionalization of alkynes using TsNBr2
Ketones are the most important class of functional group due to their abundance in many
natural products, biologically active molecules, pharmaceuticals, cosmetics, dyes, fragrances,
agriculture etc.3 Besides their high biological and industrial value, they are considered as the
prime choice for synthetic chemists as several organic compound can be made using ketones as
starting materials. Hydration of alkynes is a commonly used method for the synthesis of ketones.
Traditionally, it is carried out by using highly toxic mercury as a catalyst in presence of a mineral
acid such as sulfuric acid.4 Later on, mercury was replaced by some other catalysts based on
transition metals such as Ru,5 Au,6 Fe,7 Ag,8 In9 and Co.10 However, the use of expensive and
toxic metals limits the application of such methods to a greater extent. Reports on the use of
ionic liquid to enhance the efficiency of such hydration processes are also known.11
Debromination of α,α-dibromoketones and α-bromoketones is an alternative way to synthesize
3

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ketone.12 Functionalization of alkynes using TsNBr2 to produce dibromo ketons or acetals is
known in the literature.13, 2h During our investigation on the issue of alkyne functionalization
using TsNBr2 we found that alkynes can directly be converted to ketones through an
oxybromination-debromination sequence. To the best of our knowledge, this is the first report for
direct synthesis of ketones from alkyne using this strategy. This particular investigation also led
us to develop a transition metal free method for the synthesis of α-bromo ketones from alkynes.
2. Results and Discussion
Initial investigations for conversion of alkyne to ketone were carried out using
phenylacetylene as the model substrate. To a stirred solution of phenylacetylene (1 mmol) in a
solvent comprised of acetone (3 mL) and water (0.1 mL), TsNBr2 (1.5 mmol) was added at room
temperature. After stirring the reaction mixture for 10 minutes, KI (0.3 mmol) and Na2SO3 (2
mmol) were added and the reaction was continued at room temperature. After 3h of stirring at
room temperature, the reaction produced acetophenone in 65% isolated yield along with a minor
amount of dibromoketone (Table 1, entry1). Then the reaction was carried out using 3 mmol of
Na2SO3 and the yield of corresponding ketone was found to be 70% (Table1, entry 2).
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Table 1: Optimization of reaction conditions for synthesis of ketone from alkynea
O
TsNBr2,
KI, Na2SO3
CH3
H2O, solvent, rt
Catalyst
(mmol)
Entry
Solvent (mL)
Na2SO3
(mmol)
Time
Yields (%)b
KI
(0.3)
KI
Acetone
Acetone
Acetone
3h
3h
2h
65
70
80
1
2
3
4
2
3
3
3
(0.3)
KI
(0.5)
KI
Acetone
2h
85
(0.6 )
NaI
5
Acetone
3
2h
80
(0.6 )
I2
6
7
8
Acetone
Acetone
3
4
18h
6h
82
68
(0.6)
Na2S
(0.3)
KI
Acetonitrile
3
3
3h
4h
80
(0.6)
Ethylacetate-Acetone
(2:1)
KI
75
9
(0.6)
a
b
Reaction conditions: alkyne (1 mmol), TsNBr2 (1.5 mmol), solvent (3 mL), H2O (0.1 mL).
isolated yield
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Hence, the reaction was further examined by increasing the amount of KI which resulted in
gradual increase of the yield of the desired ketone (80-85%, Table 1, entry 3, 4). Interestingly,
further increase in KI could not improve the results. Inferior results were found when the
reaction was also studied by replacing KI with NaI, I2 and Na2S (Table 1, entry 5-7). Use of
other solvent systems could not produce better results (Table 1, entry 8, 9). With the optimized
reaction conditions in hand (Table 1, entry 4), the protocol was extended to a number of
alkynes. Results are summarized in Table 2.
Table 2: Substrate scope for synthesis of ketonesa
TsNBr2, KI, Na2SO3
Acetone/H2O, rt
O
R
R
1a-k
2a-k
O
O
O
O
C3H7
2a, 85%
2b, 83%
2d, 81%
2c, 80%
O
O
O
O
MeO
Br
F
2f, 82%
2g, 82%
2h, 82%
2e, 87%
O
O
O
Cl
2j, 79%
2k, 83%
2i, 81%
a
Reaction conditions: alkyne (1 mmol), TsNBr2 (1.5 mmol), KI (0.6 mmol), Na2SO3 (3 mmol), H2O (0.1 mL),
Acetone (3 mL), 2h, isolated yields.
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It can be seen from the table that both aliphatic as well as aromatic terminal alkynes provided the
corresponding ketones in very high yield (2a-2j) within a short time. The reaction was found to
be highly regioselective with exclusive formation of corresponding ketons. During the reaction
we have isolated α,α-dibromoketones in some cases. Based on this observation, a probable
mechanism can be sketched with the involvement of a α,α-dibromoketone at the initial stage of
the reaction which further proceeds via a halogen-exchange reaction (Scheme 2).12f, g, 13 We
observed that, the addition of a KI is essential for elimination of both the bromines from the in-
situ generated dibromoketone. Reaction with Na2SO3 in absence of KI led to the formation of α-
bromoketone even after a long exposure. The reaction perhaps proceeds via a halogen-exchange
reaction of the in-situ generated dibromoketone with I– to generate α-iodo,α-bromo-ketone
because I– serves both as a good nucleophile and a good leaving group. Further reaction with
Na2SO3 facilitates the elimination of I– which subsequently takes part in the catalytic cycle.
Repetition of the cycle produces the desired ketone.
O
O
O
Br
I
TsNBr2
I
Na2SO3
KI
OS
Br
-I
O-
CH3COCH3:H2O
Br
Br
O
O
Br
H2O
O
O
O
O
Br
I
I
Na2SO3
I
-I
H2O
OS
O-
Scheme 2: Proposed mechanism for oxybromination-debromination reaction
7

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After successful synthesis of ketones from alkynes, we looked for the possibility of
synthesizing α-bromoketones by selectively removing one of the bromine atoms from the
intermediate dibromoketone. α-Bromoketones are widely used in synthetic organic chemistry as
well as in medicinal chemistry.14 Usually, α-bromoketones are prepared via bromination of
corresponding carbonyl compounds.15 Very recently, we have also developed a method for the
synthesis of α-bromoketones from olefins using TsNBr2 under mild conditions.2j
During our investigation, we envisioned that, selective mono-debromination of α,α-
dibromoketones can be used as an wonderful strategy for direct synthesis of α-bromoketone
from alkyne. Since, α,α-dibromoketones can be very easily synthesized from alkyne,13 we
desired to investigate the possibility of direct conversion of alkyne to α-bromoketone via
selective mono-debromination. Till date, to the best of our knowledge, only one report is
mentioned in literature for the direct, one pot synthesis of α-bromoketone from alkyne. Zhang et
al. reported synthesis of bromomethyl ketones from alkyne in one step using a gold catalyst
Ph3PAuNTf2 and 8-methylquinoline-N-oxide as oxidant.16 The reaction was carried out at room
temperature using 1,2-dichloroethane or 1,2-dibromoethane as a solvent which itself act as
halogen source and the reaction completes usually within 8h. Syntheses of α-bromoketones via
hydration of haloalkynes are reported in literature.7, 17 With our plan in mind, a reaction was
carried out by treating phenyl acetylene (1 mmol) with TsNBr2 (2 mmol) in a mixture of
acetonitrile (4 mL) and water (1 mL) at room temperature. The reaction could produce only α,α-
dibromoketone even after 24h of reaction. When the reaction was carried out in a binary mixture
of acetone and water in 30:1 ratio (3 mL) at room temperature for 30h, corresponding α-
bromoketone was produced in 50 % yield along with corresponding α,α-dibromoketone. Next,
the process was investigated by adding Na2SO3 to the reaction mixture. In this case, initially,
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phenylacetylene (1 mmol) was treated with TsNBr2 (2 mmol) for 10 min followed by the
addition of Na2SO3 (4 mmol). This modification could increase the yield to 60 % in 30h at room
temperature (Table 3, entry 2). Yield of the product could not be improved by increasing the
amount of Na2SO3 from 4 mmol to 6 mmol.
Table 3: Optimization of reaction conditions for synthesis of α-bromoketone a
O
TsNBr2, Na2SO3,
H2O, Solvent, rt
Br
Solvent
(mL)
TsNBr2 Na2SO3 Time
(mmol) (mmol) (h)
Entry
Yields (%)b
50
60
1
2
Acetone -H2O c
2
2
2
-
30
Acetone-H2O c
Acetone-H2O c
4
30
60
3
6
24
70
4
5
Ethyl acetate-Acetone –H2O d
6
24
2
Ethyl acetate-Acetone –H2O d
2
8
24
80
a Reaction conditions: alkyne (1 mmol), b isolated yield. cAcetone (3 mL)-H2O (0.1 mL); dEtOAc (1mL),
CH3COCH3-H2O (1:1 ratio, 0.1 mL);
When the reaction was further studied with a slight modification of the solvent system
from acetone-water to Ethyl acetate-acetone-water system, improvement of yield was observed.
Thus taking of 1 mL ethyl acetate along with 0.1 mL acetone-water (1:1) as a solvent increased
the reaction yield up to 70% and the reaction get completed within 24h (Table 3, entry 4).
Further increment in Na2SO3 amount to 8 mmol resulted in remarkable improvement of the
yield. Thus, addition of Na2SO3 (8 mmol) after initial mixing of alkyne (1 mmol) and TsNBr2 (2
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mmol) for 15 mins in ethyl acetate-acetone-water (1.1 mL) could readily afford the desired α-
bromo ketone with 80% yield in 24h at room temperature (Table 3, entry 5).
Table 4: Synthesis of α-bromoketones from alkynesa
O
TsNBr2, Na2SO3,
Br
R
R
EtOAc/Acetone/H2O, rt
1a-k
3a-k
O
O
O
Br
Br
Br
Br
F
3a, 80%
3b, 79%
3c, 79%
O
O
O
Br
Br
Br
Cl
3e, 80%
3d, 77%
3f, 80%
O
O
O
O
Br
Br
CH3
Br
C3H7
3i, 78%
3h, 75%
3g, 77%
O
O
Br
Br
3j, 60%
3k, 74%
a Reaction conditions: alkyne (1 mmol), TsNBr2 (2 mmol), Na2SO3 (8mmol), EtOAc (1ml), CH3COCH3-H2O (0.1
mL), 24 h; b isolated yield.
After getting the optimized conditions for α-bromoketone synthesis, we examined the scope of
the reaction for different alkynes (Table 4).
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From the table it is clear that aromatic alkynes produced excellent result under this
reaction condition. However, relatively lower yield was obtained in case of aliphatic alkyne such
as 1-octyne. In all cases, exclusive formation of α-bromoketones was observed. After
establishing two different approaches for oxidative functionalization of alkynes, we looked for
more applications of TsNBr2 for the activation of C-C triple bond. It is well known that 1-
haloalkynes, particularly 1-bromoalkynes, belong to important class of synthons used for various
organic transformations.17, 18 In addition, 1-haloalkynes are important building blocks in material
and polymer polymer science.19 Literature review reveals that the most common method adopted
for synthesis of bromoalkynes involve bromination of terminal alkynes using NaOH/Br2,20 n-
BuLi/Br2,21 n-BuLi/NBS,22 DBU/Cl3CBr,23 CBr4/KOH/18-crown-6,24 PPh3/CBr4 systems..
25
Application of Au and Ag catalysts has also been reported to promote the bromination of alkynes
using NBS.26 Michel et al. developed a one pot procedure for the synthesis of bromoalkynes
from aldehydes using dibromomethyltryphenylphosphonium bromide in presence of t-BuOK at -
78° C.27 Li et al. reported recently the use of NBS in presence of DBU for the synthesis of 1-
bromoalkynes.28 In continuation of our work on TsNBr2, we have examined the efficacy of the
reagent towards synthesis of 1-bromoalkynes from alkyne.
Following our earlier protocols, we have carried out the initial studies on 1-bromoalkyne
synthesis taking phenylacetylene as a standard substrate to find out the most suitable reaction
conditions. In a typical reaction, TsNBr2 (1 mmol) was added to a solution of phenylacetylene (1
mmol) and DBU (1.2 mmol) in DCM (3ml) and the mixture was stirred at room temperature. It
was observed that the reaction goes to completion within 5-10 mins with almost 90% yield
(Table 5, entry 1). Next, the concentration of TsNBr2 was increased to 1.2 mmol which resulted
in 96% yield of the desired product within same duration of the reaction (Table 5, entry 2).
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Lowering the concentration of TsNBr2 to 0.5 mmol subsequently lowered the yield to 70% after
30 min of reaction. The use of different bases such as K2CO3, KOH as well as solvents such as
THF and DMF could not produce encouraging results. The use of acetonitrile as solvent had
similar impact on the reaction yield as compared to the performance of dichloromethane for this
particular reaction (Table 5, entry 7).
Table 5: Optimization of reaction conditions for synthesis of 1-bromoalkynesa
Br
TsNBr2, DBU
Solvent, RT
Entry
Solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
THF
Base
TsNBr2 (equiv.)
Time (mins)
Yield (%)b
1
2
3
4
5
6
7
8
9
DBU (1.2)
DBU (1.2)
DBU (1.2)
K2CO3 (1.2)
KOH (1.2)
DBU (1.0)
DBU (1.2)
DBU (1.2)
DBU (1.2)
1
5
5
90
96
1.2
0.5
1.2
1.2
1.2
1.2
1.2
1.2
5
70
120
120
60
5
10
Trace
75
95
30
10
70
DMF
92
a Reaction conditions: Acetylene (1 mmole), TsNBr2 (1.2 mmole), DBU (1.2 mmole), CH2Cl2 (3ml), rt. b isolated
yield.
After optimizing the reaction conditions, the reaction was extended for variety of substrates. The
results are summarized in Table 6. It was observed that the reaction works well for variety of
substituted phenylacetylene and aliphatic terminal alkynes as well. With aliphatic terminal
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alkynes the yield and the reaction time is slightly lower and longer respectively in comparison to
the phenylacetylene. Addition of the nonnucleophilic base DBU helps in abstraction of proton
from alkyne, which subsequently picks up Br+ ion from TsNBr2. Since, TsNBr2 is an excellent
source of Br+ species,2e formation of corresponding bromoalkyne is very facile in this case.
Table 6: Substrate scope for synthesis of 1-bromoalkynesa
TsNBr2, DBU
R
R
Br
CH2Cl2, rt
5a-k
1a-k
Br
Br
Br
Br
MeO
(H3C)3C
5a, 5 min, 96%
5b, 5 min, 92%
5c, 5 min, 95%
5d, 5 min, 93%
Br
Br
Br
C3H7
Br
Br
5g, 5 min, 92%
5f, 5 min, 95%
5h, 15 min, 85%
5e, 10 min, 90%
OAc
O
O
Br
Br
N
Br
Br
AcO
OAc
5i, 20 min, 87%
5j, 20 min, 81%
OAc
5k, 15 min, 90%
5l, 45 min, 61%
a
b
Reaction conditions: Acetylene (1 mmol), TsNBr2 (1.2 mmol), DBU (1.2 mmol), CH2Cl2 (3 mL), rt. isolated
yield.
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3. CONCLUSION
In conclusion, we have developed few highly efficient protocols for functionalization of alkynes
using TsNBr2 without any catalyst. Successive treatment of an alkyne with TsNBr2, KI and
Na2SO3 in a mixture of acetone and water at room temperature could produce corresponding
ketone in excellent yield. Similarly, α-bromoketones could be produced from corresponding
alkynes by treating with TsNBr2 and Na2SO3 in a mixture of ethyl acetate, acetone and water at
room temperature. The method is highly efficient and can be used as an alternative for classical
metal catalysed hydration of alkynes. In addition, TsNBr2 has also been found to be an effective
bromine source for the synthesis of 1-bromoalkyne from alkyne in presence of DBU under very
mild reaction conditions.
4. EXPERIMENTAL SECTION
4.1. General Remarks. All reagents and starting materials were purchased from commercial
13
sources. 1H NMR and C NMR spectra were recorded in Bruker Ultrashield 300/600 NMR and
Varian 400 NMR spectrometer. Chemical shifts are given in δ units relative to the
tetramethylsilane (TMS) signal as an internal reference in CDCl3. Coupling constants (J) are
reported in hertz. IR spectra were recorded in IR Affinity-1 (SHIMADZU) spectrometer.
Chromatographic purification was performed using flash chromatography over a manually
packed column containing silica gel (230-400 mesh).
4.2. General procedure for synthesis of ketones (2a-2k):
To a stirred solution alkyne (1 mmol) in acetone (3 mL) and water (0.1 mL), TsNBr2 (1.5 mmol)
was added. After 10 min, KI (0.6 mmol) and Na2SO3 (3 mmol) was added and stirring was
14

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continued at room temperature. After the completion of the reaction the reaction mixture was
washed with water and extracted with ethylacetate. The organic layer was dried with Na2SO4,
concentrated and purified by flash chromatography on silica gel (230-400 mesh) using petroleum
ether-ethyl acetate as eluent.
1
4.2.1. Acetophenone (2a):6a Colorless liquid (102 mg, 87%); H NMR (CDCl3, 300 MHz): δ
7.90-7.97 (m, 2H), 7.54-7.59 (m, 1H), 7.43-7.48 (m, 2H), 2.60 (s, 3H); 13C NMR (CDCl3, 75
MHz): δ 198.1, 136.9, 133.0, 128.4, 128.2, 26.5; IR (KBr, cm-1): ν 2969, 2911, 1691, 1601,
1450, 1368, 1180, 955.
4.2.2. 1-p-Tolylethanone (2b):6b Colorless liquid (111 mg, 83%); 1H NMR (CDCl3, 300 MHz):
δ 7.86 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 7.8 Hz, 2H), 2.58 (s, 3H), 2.41 (s, 3H); 13C NMR (CDCl3,
75 MHz): δ 197.8, 143.8, 134.5, 129.1, 128.3, 26.4, 21.5; IR (KBr, cm-1): ν 2984, 2907, 1699,
1373, 1234, 1042.
1
4.2.3. 1-m-Tolylethanone (2c):6b Yellow liquid (107 mg, 80%); H NMR (CDCl3, 300 MHz): δ
7.76 (d, J = 7.8 Hz, 2H), 7.39-7.34 (m, 2H), 2.59 (s, 3H), 2.41 (s, 3H); 13C NMR (CDCl3, 75
MHz): δ 198.3, 138.2, 136.9, 133.7, 128.6, 128.3, 125.4, 26.5, 21.2; IR (KBr, cm-1): ν 2944,
2913, 1680, 1422, 1273, 1193, 784.
1
4.2.4. 1-(4-Propylphenyl)ethanone (2d):6b Colorless oil.(131 mg, 81%); H NMR (CDCl3, 300
MHz): δ 7.88 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.1 Hz, 2H), 2.62 (t, J = 7.2 Hz, 2H), 2.58 (s, 3H),
1.66 (sext, J = 7.5 Hz, 2H), 0.94 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 197.9, 148.5,
134.7, 129.5, 128.4, 37.7, 27.3, 24.2, 12.9; IR (KBr, cm-1): ν 2971, 2871, 1687, 1581, 1449,
1358, 1221, 1159, 751.
4.2.5. 1-(4-Tert-butylphenyl)ethanone (2e):6b Colorless liquid (153 mg, 87%); 1H NMR (CDCl3,
13
300 MHz): δ 7.91 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H), 2.59 (s, 3H), 1.34 (s, 3H); C
15

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NMR (CDCl3, 75 MHz): δ 197.8, 156.7, 134.4, 128.2, 125.4, 35.0, 30.9, 26.5; IR (KBr, cm-1): ν
2968, 2902, 1683, 1604, 1356, 1270, 1112, 956.
4.2.6. 1-(4-Methoxyphenyl)ethanone (2f):6b White solid (123 mg, 82%); mp. 36-38 °C. 1H NMR
(CDCl3, 300 MHz): δ 7.86 (d, J = 8.7 Hz, 2H), 6.86 (d, J = 9 Hz, 2H), 3.79 (s, 3H), 2.48 (s, 3H);
13C NMR (CDCl3, 75 MHz): δ 196.5, 163.2, 130.3, 129.9, 113.4, 55.1, 26.0; IR (KBr, cm-1): ν
2963, 2914, 1682, 1510, 1429, 1367, 1269, 832.
1
4.2.7. 1-(4-Bromophenyl)ethanone (2g):29 Yellow solid ( 163 mg, 82%); mp (49-50 °C). H
13
NMR (CDCl3, 300 MHz): δ 7.81 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 2.58 (s, 3H); C
NMR (CDCl3, 150 MHz): δ 197.0, 135.8, 131.8, 129.8, 128.3, 26.5; IR (KBr, cm-1): ν 2966,
2902, 1674, 1566, 1431, 1364, 1025, 825 .
4.2.8. 1-(4-Fluorophenyl)ethanone (2h):6b Colorless liquid (113 mg, 82%); 1H NMR (300 MHz,
CDCl3): δ 7.86-7.91 (m, 2H), 7.00-7.05 (m, 2H), 2.49 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ
196.2, 165.4 ( d, JCF = 252.6 Hz), 133.2, 130.7 (d, JCF = 9.3 Hz), 115.3 (d, JCF = 21.9 Hz), 26.2;
IR (KBr, cm-1): ν 2993, 2926, 1687, 1505, 1408, 1360, 1233, 1014, 718.
1
4.2.9. 1-(4-chlorophenyl)ethanone (2i):6b Colorless oil (125 mg, 81%); H NMR (CDCl3, 300
MHz): δ 7.77 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 2.47 (s, 3H); 13C NMR (CDCl3, 150
MHz): δ 196.5, 139.2, 135.2, 129.5, 128.6, 26.3; IR (KBr, cm-1): ν 2968, 2924, 1687, 1518,
1429, 1358, 1261, 1013, 829.
4.2.10. Octan-2-one (2j):30 Colorless oil (101 mg, 79%); 1H NMR (CDCl3, 300 MHz): δ 2.41 (t,
J = 7.8 Hz, 2H), 2.12 (s, 3H), 1.62-1.47 (m, 2H), 1.35-1.18 (m, 6H), 0.86 (t, J = 6.3 Hz, 3H); 13C
NMR (CDCl3, 150 MHz): δ 208.6, 43.4, 31.3, 29.4, 28.6, 23.5, 22.2, 13.7; IR (KBr, cm-1) ν 2963,
2874, 1718, 1468, 1361, 1116, 1009, 777.
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1
4.2.11. Butyrophenone (2k):34 Reddish brown oil (122 mg, 83%); H NMR (CDCl3, 300 MHz):
δ 7.96 (d, J = 7.8 Hz, 2H), 7.55 (t, J = 6.9 Hz, 1H), 7.45 (t, J = 6.9 Hz, 2H), 2.95 (t, J = 6.6 Hz,
13
2H), 1.80-1.73 (m, 2H), 1.00 (t, J = 6.9 Hz, 3H); C NMR (CDCl3, 100 MHz): δ 200.4, 137.0,
132.8, 128.5, 128.0, 40.5, 17.7, 13.8; IR (KBr, cm-1) ν 2965, 2921, 1681, 1605, 1454, 1222, 701.
4.3 General procedure for synthesis of α-bromoketones (3a-3k):
To a stirred solution of alkyne (1 mmol) in ethylacetate (1 ml), 0.1 ml of acetone:water (1:1) and
TsNBr2 (2 mmol) was added. After 10 min Na2SO3 (8 mmol) was added and the reaction was
stirred at room temperature till completion as monitored by TLC. The organic layer was
extracted with ethylacetate, washed with water, dried with Na2SO4 and concentrated. The crude
product was purified by flash chromatography on silica gel (230-400 mesh) using petroleum
ether-ethyl acetate as eluent.
1
4.3.1. 2-Bromo-1-phenylethanone (3a):2j White solid (160 mg, 80%); mp. 48-49 °C. H NMR
(CDCl3, 300 MHz): δ 7.98 (d, J = 7.8, 2H), 7.64-7.59 (m, 1H), 7.48 (d, J = 7.2, 2H), 4.46 (s, 2H);
13C NMR (CDCl3, 75 MHz): δ 191.3, 133.9, 133.8, 128.9, 128.8, 30.9; IR (KBr, cm-1) ν 1690,
1614, 1469, 1294, 1191, 780.
4.3.2. 2-Bromo-1-(4-bromophenyl)ethanone (3b):2j White solid (219 mg, 79%); mp (99-102
°C). 1H NMR (CDCl3, 300 MHz): δ 7.84 (d, J = 8.7 Hz, 2H,), 7.63 (d, J = 8.7 Hz , 2H), 4.41 (s,
2H); 13C NMR (CDCl3, 75 MHz): δ 190.3, 132.5, 132.1, 130.3, 129.2, 30.4; IR (KBr, cm-1) ν
1694, 1593, 1390, 1283, 1206, 1075, 815.
4.3.3. 2-Bromo-1-(4-fluorophenyl)ethanone (3c):2j White solid (171 mg, 79%); mp. 45-47 °C.
1H NMR (CDCl3, 300 MHz): δ 8.01-7.96 (m, 2H), 7.15-7.10 (m, 2H), 4.42 (s, 2H); 13C NMR
17

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(CDCl3, 75 MHz): δ 189.8, 166.0 (d, JCF = 247.6 Hz), 131.7 (d, JCF = 9.8 Hz), 130.9, 116.0 (d,
JCF = 21.9 Hz), 30.4; IR (KBr, cm-1): ν 1683, 1600, 1510, 1280, 1235, 1195, 993, 830, 760.
4.3.4. 2-Bromo-1-(4-chlorophenyl)ethanone (3d):2j White solid (180 mg, 77%); mp. 92-94 °C.
1H NMR (CDCl3, 300 MHz): δ 7.93 (d, J = 8.1 Hz, 2H ), 7.47 (d, J = 8.4 Hz, 2H ), 4.41 (s, 2H);
13 C NMR (CDCl3, 75 MHz): δ 190.1, 140.5, 132.1, 130.3, 129.2, 30.4; IR (KBr, cm-1): ν 1695,
1590, 1406, 1202, 1090, 996, 813, 760.
1
4.3.5. 2-Bromo-1-p-tolylethanone (3e):2j White solid (170 mg, 80%); mp.45-47 °C. H NMR
(CDCl3, 300 MHz): δ 7.89 (d, J =8.1 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 4.44 (s, 2H), 2.43 (s,
13
3H); C NMR (CDCl3, 75 MHz): δ 190.9, 145.0, 131.7, 129.5, 129.0, 30.9, 21.7; IR (KBr, cm-
1): ν 1690, 1605, 1390, 1280, 1220, 1175, 970, 798, 680.
1
4.3.6. 2-Bromo-1-m-tolylethanone (3f):2j Colorless oil (170 mg, 80%); H NMR (CDCl3, 300
MHz): δ 7.77 (d, J = 8.4 Hz, 2H), 7.43-7.37 (m, 2H), 4.46 (s, 2H), 2.42 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 191.4, 138.7, 134.7, 133.8, 129.2, 128.6, 126.0, 31.1, 21.3; IR (KBr, cm-1):
ν 1681, 1562, 1535, 1485, 1285, 690.
1
4.3.7. 1-(4-Tert-butylphenyl)-2-bromoethanone (3g):2j Colorless oil (196 mg, 77%); H NMR
(CDCl3, 300 MHz): δ 7.94 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.7 Hz, 2H), 4.45 (s, 2H), 1.35 (s,
13
9H); C NMR (CDCl3, 75 MHz): δ 190.9, 157.9, 131.2, 128.9, 125.8, 35.2, 30.9; IR (KBr, cm-
1): ν 1685, 1605, 1560, 1465, 1285, 1196, 1105, 1010, 845, 668.
1
4.3.8. 2-Bromo-1-(4-propylphenyl)ethanone (3h):31 Colorless oil (180 mg, 75%); H NMR
(CDCl3, 300 MHz): δ 7.91 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 4.45 (s, 2H), 2.66 (t, J =
13
7.2 Hz, 2H), 1.74-1.63 (m, 2H), 0.96 (t, J = 6.9 Hz, 3H); C NMR (CDCl3, 75 MHz): δ 190.9,
149.7, 131.6, 129.0, 128.9, 38.1, 31.0, 24.1, 13.7; IR (KBr, cm-1): ν 1680, 1605, 1264, 1182,
1011, 736.
18

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1
4.3.9. 2-Bromo-1-phenylbutane-1, 3-dione (3i):2j Yellow oil (188 mg, 78%); H NMR (CDCl3,
300 MHz): δ 8.00 -7.97 (m, 2H), 7.67-7.61 (m, 1H),7.55-7.43 (m,2H), 5.63 (s, 1H), 2.46 (s, 3H);
13 C NMR (CDCl3, 75 MHz): δ 198.2, 189.8, 134.5, 133.6, 129.2, 128.9, 52.9, 27.1; IR (KBr, cm-
1): ν 1732, 1680, 1218, 760, 670.
1
4.3.10. 1-bromooctan-2-one (3j): 2j Yellow oil (124 mg, 60%); H NMR (CDCl3, 300 MHz): δ
3.89 (s, 2H), 2.65 (t, J = 7.8 Hz, 2H), 1.70-1.56 (m, 2H), 1.29-1.21 (m, 6H), 0.88 (t, J = 6Hz,
3H); 13 C NMR (CDCl3, 100 MHz): δ 202.4, 40.0, 34.4, 31.6, 28.9, 24.0, 22.6, 14.1; IR (KBr,
cm-1): ν 1730, 1665, 1580, 1435, 1265, 720, 670.
1
4.3.11. 2-Bromo-1-phenylbutane-1-one (3k):35 Yellow oil (167 mg, 74%); H NMR (CDCl3,
300 MHz): δ 7.44 (d, J = 5.4 Hz, 2H), 7.39-7.36 (m, 3H), 5.47 (s, 1H), 2.67-2.60 (m, 2H), 1.06
(t, J = 7.2 Hz, 3H); 13 C NMR (CDCl3, 100 MHz): δ 202.2, 135.4, 130.1, 129.1, 129.0, 128.8,
128.7, 55.4, 32.4, 8.2; IR (KBr, cm-1): ν 1690, 1595, 1450, 1221, 1010, 901, 705.
4.4 General procedure for synthesis of 1-bromoalkyne (5a-5l):
To a stirred solution of alkyne (1 mmol) in CH2Cl2 (3 ml), TsNBr2 (1.2 mmol) and DBU (1.2
mmol) was added. The progress of the reaction was monitored by TLC. After the completion of
the reaction sodium thiosulfate (200 mg) was added to the reaction mixture and further stirred for
5 mins. The reaction mixture was washed with water and extracted with ethylacetate. The
organic layer was separated and dried over Na2SO4 and concentrated in vaccuo. Purification of
the crude product by flash chromatography on silica gel (230-400 mesh) with petroleum ether as
eluent gave the desired product.
19

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20
1
4.4.1 1-Bromoethynyl-benzene (5a): Colorless oil (173 mg, 96%); H NMR (CDCl3, 300
MHz): δ 7.47-7.51 (m, 2H), 7.32-7.38 (m, 3H); 13C NMR (CDCl3, 75 MHz): δ 131.9, 128.6,
128.2, 122.6, 79.9, 49.7; IR (KBr, cm-1): ν 2922, 2196, 1594, 1481, 1443, 1213, 1064, 749.
4.4.2 1-Bromoethynyl-4-methyl-benzene (5b): 20 Colorless oil (179 mg, 92%); 1H NMR (CDCl3,
13
300 MHz): δ 7.38 (d, J = 7.8 Hz, 2H), 7.15 (d, J = 7.8 Hz, 2H), 2.38 (s, 3H); C NMR (CDCl3,
75 MHz): δ 138.7, 131.7, 129.0, 119.5, 80.0, 48.75, 21.4; IR (KBr, cm-1): ν 2925, 2846, 1688,
1594, 1481, 1443, 1208, 746, 680.
20
1
4.4.3. 1-Bromoethynyl-4-methoxy-benzene (5c):
Colorless oil (200 mg, 95%); H NMR
13
(CDCl3, 300 MHz): δ 7.34-7.42 (m, 2H), 6.82-6.92 (m, 2H), 3.81 (s, 3H); C NMR (CDCl3, 75
MHz): δ 159.7, 133.3, 113.8, 113.7, 79.8, 55.3, 47.8; IR (KBr, cm-1): ν 2921, 2846, 1603, 1500,
1452, 1245, 1170, 1029, 821.
1
4.4.4. 1-Bromoethynyl-4-tert-butyl-benzene (5d):20 Colorless oil (220 mg, 93%); H NMR
(CDCl3, 300 MHz): δ 7.44 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.7 Hz, 2H), 1.36 (s, 9H); 13C NMR
(CDCl3, 75 MHz): δ 151.8, 131.6, 128.4, 125.2, 119.6, 80.0, 48.7, 34.7, 31.0; IR (KBr, cm-1): ν
2938, 2856, 1688, 1500, 1462, 1358, 1264, 1108, 837.
1
4.4.5. 1-Bromoethynyl-3-methyl-benzene (5e):20 Yellow oil (175 mg, 90%); H NMR (CDCl3,
300 MHz): δ 7.31 (d, J = 6 Hz, 2H), 7.24 (s, 1H), 7.21 (d, J = 3 Hz, 1H) 2.37 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 137.9, 132.4, 129.5, 128.9, 128.1, 122.3, 80.1, 49.2, 21.0; IR (KBr, cm-1): ν
2921, 2853, 1689, 1597, 1481, 1265, 1165, 784.
1
4.4.6. 1-Bromoethynyl-4-propyl-benzene (5f):32 Yellow oil (211 mg, 95%); H NMR (CDCl3,
300 MHz): δ 7.38 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 2.60 (t, J = 7.8 Hz, 2H), 1.59-
1.71 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 143.5, 131.82, 128.4,
20

ACCEPTED MANUSCRIPT
119.7, 80.1, 48.7, 37.9, 24.2, 13.7; IR (KBr, cm-1): ν 2930, 2868, 1689, 1504, 1451, 1264, 1173,
826.
1
4.4.7. 1-Bromo-4-bromoethynyl-benzene (5g):17a White solid (238 mg, 92%); mp. 96-98°C. H
NMR (CDCl3, 300 MHz): δ 7.45 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3,
75 MHz): δ 133.3, 131.5, 122.9, 121.5, 78.9, 51.2; IR (KBr, cm-1): ν 2919, 2845, 1689, 1643,
1542, 1458, 1211, 803.
1
4.4.8. 1-Bromo-dec-1-yne (5h):33 Colorless oil (184 mg, 85%); H NMR (CDCl3, 300 MHz): δ
2.19 (t, J = 6.3 Hz, 2H), 1.48-1.55 (m, 2H), 1.28-1.38 (m, 10H), 0.88 (t, J = 6.9 Hz, 3H); 13C
NMR (CDCl3, 75 MHz): δ 80.3, 37.3, 31.8, 29.1, 29.0, 28.7, 28.4, 22.6, 19.6, 14.0; IR (KBr, cm-
1): ν 2923, 2846, 1557, 1452, 1371, 1240, 723, 624.
1
4.4.9. 1-Bromo-oct-1-yne (5i):27d Colorless oil (164 mg, 87%); H NMR (CDCl3, 300 MHz): δ
2.67 (t, J = 7.8 Hz, 2H), 1.56-1.63 (m, 2H), 1.25-1.36 (m, 6H), 0.90 (t, J = 6.9 Hz, 3H); 13C
NMR (CDCl3, 75 MHz): δ 86.7, 40.8, 31.4, 28.1, 28.0, 27.4, 22.5, 14.0; IR (KBr, cm-1): ν 2928,
2855, 1549, 1443, 1388, 718, 630.
1
4.4.10. 1-Bromo-hex-1-yne (5j):32 Colorless oil (130 mg, 81%); H NMR (CDCl3, 300 MHz): δ
2.68 (t, J = 7.2 Hz, 2H), 1.55-1.62 (m, 2H), 1.33-1.41 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 75 MHz): δ 86.7, 40.6, 29.6, 29.6, 21.6, 13.8; IR (KBr, cm-1): ν 2924, 2851, 1556,
1450, 1381, 733, 619.
4.4.11. 2-Bromoethynyl-pyridine (5k):24 Brown oil (162 mg, 90%); 1H NMR (CDCl3, 300 MHz):
δ 8.56 (d, J = 4.2 Hz, 1H), 7.66 (t, J = 7.5 Hz, 1H), 7.43 (d, J = 7.5 Hz, 1H), 7.27 (t, J = 4.8 Hz,
1H); IR (KBr, cm-1): ν 2941, 1699, 1477, 1451, 1050, 781.
4.4.12. 3’-Bromo-2’-propynyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (5l):36 Colorless gum
(283 mg, 61%); 1H NMR (CDCl3, 300 MHz): δ 5.24-5.11 (m, 1H), 5.08-5.05 (m, 2H), 4.82 (d, J
21

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= 13.2 Hz, 1H), 4.53-4.42 (m, 2H), 4.25-4.17 (m, 2H), 3.72 (d, J = 3.9 Hz, 1H), 2.08-2.01 (m,
12H); IR (KBr, cm-1): ν 2961, 2884, 2220, 1741, 1393, 1068.
ACKNOWLEDGMENT
Financial Support from the Department of Science and Technology (DST), India (Grant No. SR/S1/OC-
43/2011) is gratefully acknowledged.
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