Synthesis of acetylenes via dehydrobromination using solid anhydrous potassium phosphate as the base under phase-transfer conditions

Article abstract of DOI:10.1016/j.tetlet.2012.02.085

Phase-transfer catalyzed preparation of acetylenes from the corresponding vicinal dibromo compounds via double dehydrobromination using the mild solid base, anhydrous potassium phosphate, under very mild conditions is reported.

Full text of DOI:10.1016/j.tetlet.2012.02.085

Tetrahedron Letters 53 (2012) 2295–2297
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of acetylenes via dehydrobromination using solid anhydrous
potassium phosphate as the base under phase-transfer conditions
⇑
Sanaa Shenawi-Khalil, Sachin U. Sonavane, Yoel Sasson
Casali Institute of Applied Chemistry, Hebrew University of Jerusalem, Jerusalem 91904, Israel
a r t i c l e i n f o
a b s t r a c t
Article history:
Phase-transfer catalyzed preparation of acetylenes from the corresponding vicinal dibromo compounds
via double dehydrobromination using the mild solid base, anhydrous potassium phosphate, under very
mild conditions is reported.
Received 8 December 2011
Revised 1 February 2012
Accepted 17 February 2012
Available online 3 March 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Phase-transfer catalysis
Acetylenes
Dehydrobromination
Potassium phosphate
Vicinal dibromo compounds
One of the most significant achievements of phase-transfer
catalysis (PTC) in synthetic chemistry is the beneficial replacement
of hazardous and sensitive bases such as sodamide, sodium
hydride or potassium tert-butoxide in various processes with the
benign and robust aqueous sodium hydroxide. Weakly acidic sub-
bonyl compounds at 0 °C and measured the maximum base
0
strength as 18.4 > H > 15.0 after calcination of the phosphate at
180 °C.
Potassium phosphate has been utilized as an auxiliary mild base
in homogeneous metal-catalyzed processes, particularly in the
presence of base-sensitive functional groups. Buchwald disclosed
a
strates with a pK of up to 24 could be readily deprotonated using
5
0% aqueous NaOH in the presence of a PTC. Notwithstanding the
3 4
K PO as an auxiliary base for the arylation of amides and ketones
1
4
success of PTC/OH systems, some fundamental limitations still ex-
ist that restrict the widespread utility of this system. These are
mainly related to the presence of water in hydroxide solutions.
Water cannot be avoided in PTC/OH systems primarily due to the
highly hygroscopic nature of caustic bases. Consequently, reactions
under PTC/OH conditions are susceptible to side reactions such as
hydrolysis. This prompts us to offer a general solution for this lim-
itation by utilizing the solid mild base, potassium phosphate. This
base, in comparison with hydroxide ions, is milder, less basic, far
less hygroscopic and, most importantly, does not produce water
upon neutralization with acidic compounds which otherwise re-
sults in side reactions.
using copper or palladium catalysts. Potassium phosphate was also
the base of choice in the Suzuki cross-coupling reactions of aryl
triflates or halides and aryl boronic acids with Pd or Ni catalysts.5
We realized that potassium phosphate, despite its relatively low
6
basicity in aqueous medium (pK
a
of K
3
PO
4
is approximately 12), is
a very potent solid base in anhydrous systems, and is substantially
more active than potassium carbonate and potassium fluoride in
the formation and subsequent reactions of carbanion, azanions,
7
and oxanions. K
3
PO
4
has also been utilized for various other reac-
8
9
tions such as nitroaldol and the Knoevenagel condensation. Hy-
drated K PO has frequently been used in transition metal
catalyzed cross-coupling reactions.
3
4
1
0
Potassium phosphate has been recognized previously as a solid
base which possesses unique highly basic sites, particularly when
dehydrated upon calcination at 400 °C. Tada determined the basic
In our laboratory we have studied alkylations of different car-
bon acids and oxidative couplings of thiols to the corresponding
2
disulfides using solid K
3
PO
4
as the base under phase-transfer con-
7
,11
strength of potassium phosphate as H
0
= 17.2 using acidic indica-
ditions.
In the present study potassium phosphate was applied
tors and tested its catalytic activity for the decomposition of diac-
etone alcohol (4-hydroxy-4-methylpentan-2-one) in the liquid
phase at 30–55 °C. Higuchi et al. examined the activity of potas-
for the synthesis of acetylenes from olefins through double dehy-
drobromination under PTC conditions. Acetylenes are essential
and versatile intermediates in organic synthesis. They are also
3
12
sium phosphate and other solid bases in the cyanosilylation of car-
utilized extensively for the preparation of conjugated polyacetyl-
enes with potential applications in the emerging areas of molecu-
1
3
⇑
Corresponding author. Tel.: +972 26584530; fax: +972 25667064.
E-mail address: ysasson@huji.ac.il (Y. Sasson).
lar electronics and nanotechnology, as well as for the preparation
of nonlinear optical devices and linear chemical probes.14
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.02.085

2
296
S. Shenawi-Khalil et al. / Tetrahedron Letters 53 (2012) 2295–2297
Br
acetylenes in excellent yields. The selected catalyst for the process
was PEG-900. When combined with a preceding oxybromination
step this methodology offers a general practical strategy for the
conversion of olefins into acetylenes (Scheme 1). Initially an alkene
was reacted with aqueous hydrogen peroxide and concentrated
hydrobromic acid in ethanol at 80 °C to yield the corresponding
H O , HBr
R'
2
2
R'
R'
R
R
EtOH, 80 °C
Br
Br
R'
K3PO4, PEG-900
EtOH, 80 °C
KBr
K2HPO4
R
R
R
20
vicinal dibromide. The latter was then reacted with solid potas-
Br
Br
sium phosphate in ethanol in the presence of 25 mol % of PEG-
900 at 80 °C for 1.5–5 h to yield the corresponding acetylene. The
elimination reaction occurs as a stepwise process in which the first
mole of HBr is eliminated almost instantly while the elimination of
the second mole of HBr required several hours under our
conditions.
R' K3PO4, PEG-900
R
R
KBr
K HPO
2 4
EtOH, 80 °C
Br
R= phenyl, benzyl, hexyl, heptyl, octyl
R'= phenyl, H
The best results were achieved when solid potassium phos-
phate was added in two equivalent portions. The second portion
was preferably introduced after the first mole of HBr had been
eliminated to yield the intermediate bromo olefin. Kinetic mea-
surements revealed that at 80 °C the first step was complete within
only 10 min.
Scheme 1. General process for the conversion of olefins to acetylenes.
As described in the original procedure, the synthesis of phenyl
acetylene is achieved by heating b-bromostyrene with KOH in eth-
15
ylene glycol at 200 °C to give the product in 67% yield. Applica-
tion of a PTC for the synthesis of acetylenes via base-induced b-
elimination was reported by Dehmlow who demonstrated that
dehydrohalogenation of 1,2-dihalides into acetylenes proceeded
satisfactorily in a liquid–solid system using KOH and highly lipo-
philic tetraoctylammonium bromide as the phase-transfer cata-
This synthetic protocol (Scheme 1) was applied with several
olefins and the results are summarized in Table 1. Complete con-
version was confirmed in all the experiments using TLC and GC
analysis. The only side product detected was the corresponding
intermediate bromo olefin. We confirmed that the reaction could
be driven to completion upon addition of an excess amount of
K PO and applying a prolonged reaction time. The product acety-
1
6
lyst. It was also shown that the use of less lipophilic tetra-n-
butylammonium salts as the PT catalysts in these reactions was
3
4
1
7
not successful. A breakthrough in this field was made by Kimura
lene could be distilled from the mixture after removal of the
solvent.
1
8
and Regen who applied pentaethylene glycol as the catalyst in
the dehydrobromination of alkyl bromides or dibromides in the
presence of 60% aqueous KOH to generate olefins and acetylenes.
Typically, a 96% yield of phenyl acetylene was obtained in the reac-
tion of dibromostyrene at 70 °C after 16 h. Reasonable catalytic
activity in the latter system was also realized when pentaethylene
glycol was grafted onto a polystyrene polymer. As expected, the
presence of the highly concentrated caustic base resulted in side
reactions such as hydrolysis and polymerization of the products.
Rathore et al. used polyethylene glycol with KOH for diarylacety-
lene synthesis and obtained good yields but a very high tempera-
The reaction did not proceed at all in aprotic solvents such as
toluene or N,N-dimethylformamide. The reaction rate in n-butanol
was 50% lower than in ethanol. Potassium phosphate was com-
pletely insoluble in ethanol at temperatures below 100 °C. The
presence of polyethylene glycol did not affect this solubility. Con-
versely, when K PO was mixed with ethanol in the presence of
3
4
PEG, and following the removal of solid potassium phosphate by
filtration, the filtrate was found to be substantially basic, however
3
1
it did not contain phosphate, as was confirmed by P NMR spec-
troscopy. The transfer of basicity to the organic phase could not
therefore be attributed to extraction of phosphate. Upon addition
of an electrophile such as benzyl chloride to the ethanol/K PO /
1
9
ture (ꢀ190 °C) was required.
We report herein the application of the mild solid base, potas-
sium phosphate, in the solid–liquid phase-transfer catalyzed dou-
ble dehydrobromination reaction of vicinal dibromides to yield
3
4
PEG mixture, benzyl ethyl ether was formed instantly under ambi-
ent conditions. We concluded that the anion transferred to the
Table 1
Double dehydrobromination of vicinal dibromo compounds to the corresponding acetylenes under phase-transfer conditions via Scheme 1
Entry
Reactant
Time (h)
Product
Isolated yield (%)
93
Br
Br
Br
1
1.5
2
5.0
85
Br
Br
Br
3
4
5
6
5.0
5.0
5.0
5.0
76
61
54
52
CH -(CH ) - CH-CH
CH -(CH ) -C
CH
CH
3
2 5
2
3
2 5
Br Br
CH -(CH ) - CH-CH
CH -(CH ) -C
3 2 7
3
2 7
2
Br Br
CH -(CH ) - CH-CH
CH -(CH ) -C
CH
3
2 8
2
3
2 8
Br Br

S. Shenawi-Khalil et al. / Tetrahedron Letters 53 (2012) 2295–2297
2297
the color disappeared. The mixture was allowed to cool to room
temperature, and further neutralized by addition of aqueous NaH-
EtOH + K PO
3
4
PEG-900
EtOH
2 KBr
CO
3
solution until pH 6.
In the case of solids (Table 1, entries 1–3), the products were
separated by filtration, washed thoroughly with water and dried
in air. In the case of liquids (Table 1, entries 4–6), the products
2 2
were separated by extraction with CH Cl . The organic phase was
dried over Na SO and evaporated under vacuum, to afford pure di-
bromo compounds which were used as the reactants for the syn-
thesis of acetylenes (as detailed below).
2
4
Br
Br
K HPO
2
4
+
-
[
PEG-K ]EtO
Figure 1. Proposed mechanism for the polyethylene glycol catalyzed dehydrobro-
mination in the presence of solid K PO
Synthesis of acetylenes from vicinal dibromides
3
4
.
A mixture of vicinal dibromide (5 mmol), anhydrous K
5 mmol), PEG-900 (1.25 mmol), and EtOH (10 mL) was stirred at
0 °C. The progress of the reaction was monitored by analysis of
the samples using TLC and gas chromatography. When the vicinal
dibromide had been completely converted into the monobromo
3 4
PO
(
8
organic phase was ethoxide which is formed according to the fol-
lowing heterogeneous equilibrium:
ꢁ
þ
EtOH þ K
3
PO
4
ꢀ EtO K þ K
2 4
HPO
product, a second portion of K
Following completion of the reaction the mixture was filtered
and the filtrate was diluted with CH Cl and washed several times
with H O. The organic phase was dried over MgSO and evaporated
3 4
PO (5 mmol) was added.
Figure 1 illustrates the proposed mechanism for the PEG cata-
lyzed dehydrobromination reaction in the presence of K PO . Eth-
3
4
2
anol is deprotonated on the surface of potassium phosphate, and
potassium ethoxide is extracted into the bulk ethanol with the
aid of PEG along with the formation of K HPO . This forms the basis
2 4
2
4
under vacuum to afford a mixture of product and the monobromo
derivative. The acetylene was separated by vacuum distillation.
The identity and purity of the products were confirmed by
of the rationale for the outstanding activity of alcohols in reactions
catalyzed by phosphates, such as Knoevenagel and Michael reac-
1
GC–MS and H NMR spectroscopy.
7
tions. Potassium ethoxide in the bulk ethanol may form the com-
1
8
+
ꢁ
plex [PEG-K ]EtO which contributes to the enhanced reactivity
References and notes
ꢁ
of the EtO anion. In the second step, dehydrobromination of the
substrate occurs due to the action of [PEG-K ]EtO to produce a
vinylic bromide with both one mole of KBr and K HPO . The final
+
ꢁ
1. Makosza, M.; Fedorynski, M. Handbook of Phase Transfer Catalysis In Sasson, Y.,
Neumann, R., Eds.; Blackie Academic & Professional: London, 1997.
2
4
2
3
.
.
Tada, A. Bull. Chem. Soc. Jpn. 1975, 48, 1391.
Higuchi, K.; Onaka, M.; Izumi, Y. Bull. Chem. Soc. Jpn. 1993, 66, 2016.
step is a second dehydrobromination to produce the corresponding
acetylene.
4. (a) Klapars, A.; Huang, X. H.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421;
(b) Fox, J. M.; Huang, X. H.; Chieffi, A.; Buchwald, S. L. J. Am. Chem. Soc. 2000,
2 4
We could not identify any poisoning effect of KBr and K HPO
1
22, 1360.
on the reaction (Scheme 1), and so conclude that the latter is not
deposited on the surface of the phosphate base, where it would
block access to the active sites.
To conclude, we have demonstrated the application of anhy-
3 4
drous K PO as a mild solid base that is more potent than common
solid bases such as carbonates, oxides, or fluorides and is also more
selective than KOH or NaOH in the facile dehydrobromination of
vicinal dibromo compounds. The corresponding acetylenes were
obtained in high yields and purities under simple and mild reaction
conditions. We believe that the methodology described here can be
developed for numerous synthetic applications on laboratory and
industrial scale.
5.
(a) Ohe, T.; Miyaura, N.; Suzuki, A. J. Org. Chem. 1993, 58, 2201; (b) Inada, K.;
Miyaura, N. Tetrahedron 2001, 56, 8657.
6. Tossidis, I. Inorg. Nucl. Chem. Lett. 1976, 12, 609.
7.
8.
9.
Qafisheh, N.; Joshi, A. V.; Mukhopadhyay, S.; Sasson, Y. Ind. Eng. Chem. Res.
007, 46, 3016–3023.
Desai, U. V.; Pore, D. M.; Mane, R. B.; Solabannavar, S. B.; Wadgaonkar, P. P.
Synth. Commun. 2004, 34, 19.
2
Li, Y. Q. J. Chem. Res. Synop. 2000, 5, 524.
1
1
0. Urawa, Y.; Ogura, K. Tetrahedron Lett. 2003, 44, 271.
1. Joshi, A. V.; Bhusare, S.; Baidossi, M.; Qafisheh, N.; Sasson, Y. Tetrahedron Lett.
2005, 46, 3583.
1
1
2. Chunxiang, K.; Qing, Y.; Senboku, H.; Tokudac, M. Tetrahedron 2005, 61, 4043.
3. (a)Introduction to Molecular Electronics; Petty, M. C., Bryce, M. R., Bloor, D., Eds.;
Oxford University Press: New York, 1995; (b) McQuade, D. T.; Pullen, A. E.;
Swager, T. M. Chem. Rev. 2000, 100, 2537.
1
4. (a) Bunz, U. H. F. Chem. Rev. 2000, 100, 1605; (b) Nesterov, E. E.; Zhu, Z.; Swager,
T. M. J. Am. Chem. Soc. 2005, 127, 10083; (c) Marsden, J. A.; Palmer, G. J.; Haley,
M. M. Eur. J. Org. Chem. 2003, 2355. and references therein..
General procedures: synthesis of vicinal dibromides from
olefins
15. Hessler, J. C. In Organic Syntheses; Blatt, A. H., Ed.; Wiley: New York, 1941; Vol.
, p 438.
1
1
6. (a) Dehmlow, E. V.; Lissel, M. Tetrahedron 1981, 37, 1653; (b) Dehmlow, E. V.;
To a mixture of olefin (16.8 mmol) and EtOH (60 mL) at 80 °C
Thieser, R.; Sasson, Y.; Neumann, R. Tetrahedron 1986, 42, 3569.
was added concentrated (48%) HBr (7.2 mL) dropwise over a period
17. Gorgues, A.; Le Coq, A. Bull. Soc. Chem. Fr. 1976, 125.
18. Kimura, Y.; Regen, S. L. J. Org. Chem. 1983, 48, 195.
of 30 min followed by dropwise addition of 30% H
During H addition the color of the solution changed to brown
the characteristic color of bromine). Stirring was continued until
2 2
O (4.8 mL).
19. Shukla, R.; Brody, D. M.; Lindeman, S. V.; Rathore, R. J. Org. Chem. 2006, 71,
2 2
O
6124.
(
20. Ho, T. L.; Balarmgupta, B. G.; Olah, G. A. Synthesis 1977, 676.