Synthesis of Terminal Alkynes from anti-3-Aryl-2,3-dibromopropanoic Acids
General procedure for the synthesis of terminal al-
kynes (2)
Under the optimized conditions, the scope of the
anti-3-aryl-2,3-dibromopropanoic acids was screened
(Table 2). Unfunctionalized aromatic substrates (1b, 1c)
and electron-rich aromatic substrates (1a, 1d and 1e)
were converted to corresponding terminal alkynes with
good yields (83%—94%). Halogenated aromatic sub-
strates (1f—1l) gave excellent yields of 90%—94%.
Notably, steric congestion did not result in decreased
yields because substrates with an ortho substituent on
anti-3-aryl-2,3-dibromopropanoic acids (1h, 1i and 1l)
also worked well (92%, 91%, and 92% respectively).
However, for electron-deficient aromatic substrates
(1m—1o), decreased yields were obtained (83%, 75%,
and 80% respectively).
A mixture of anti-3-aryl-2,3-dibromopropanoic acid
1 (0.5 mmol) and K2CO3 (207 mg, 1.5 mmol) in 5 mL
of DMSO was stirred at 115 ℃ for 12 h. The mixture
was then extracted using Et2O/H2O (15 mL/20 mL×3)
after being cooled down to r.t. The organic layers were
combined, rinsed with brine, and dried over anhydrous
Na2SO4. The mixture was then evaporated to remove
the solvent, and the residue was purified by flash chro-
matography on silica gel (hexanes as eluent) to yield
products 2.
Spectral data of all synthesized compounds 2a— 2q
Challenging functionalized substrates, such as bi-
functional dibromide (1p) and pyridine (1q), were also
investigated. Both were found to be competent and gave
corresponding terminal alkynes with good or excellent
yields (98% and 72%, respectively).
1-Ethynyl-4-methylbenzene (2a)
1H NMR
(CDCl3, 500 MHz) δ: 2.33 (s, 3H, CH3), 3.01 (s, 1H,
CH), 7.10 (d, J=8.0 Hz, 2H, ArH), 7.36 (d, J=8.0 Hz,
2H, ArH).
Ethynylbenzene (2b) 1H NMR (CDCl3, 500 MHz)
δ: 3.05 (s, 1H, CH), 7.28—7.33 (m, 3H, ArH), 7.48—
7.50 (m, 2H, ArH).
The proposed reaction pathway of the present elimi-
nation is shown in Scheme 2. The reactions probably
proceeded initially via trans-elimination involving the
simultaneous loss of carbon dioxide and bromide ions to
generate the intermediates (Z)-β-arylvinyl bromides,
which had been already confirmed (Table 1, Entry 4). In
the presence of carbonate base, an E2 trans-elimination
of hydrogen bromide followed to obtain terminal al-
kynes.
2-Ethynylnaphthalene (2c) 1H NMR (CDCl3, 500
MHz) δ: 3.14 (s, 1H, CH), 7.48—7.53 (m, 3H, ArH),
7.76—7.80 (m, 3H, ArH), 8.02 (s, 1H, ArH).
1-Ethynyl-4-isopropylbenzene (2d)
1H NMR
(CDCl3, 500 MHz) δ: 1.23 (d, J=6.9 Hz, 6H, Me),
2.86—2.93 (m, 1H, MeCH), 3.02 (s, 1H, CH), 7.17 (d,
J=8.2 Hz, 2H, ArH), 7.42 (d, J=8.3 Hz, 2H, ArH).
1H NMR
Scheme 2
1-Ethynyl-4-t-butylbenzene (2e)
(CDCl3, 500 MHz) δ: 1.30 (s, 9H, t-Bu), 3.02 (s, 1H,
CH), 7.33 (d, J=8.4 Hz, 2H, ArH), 7.43 (d, J=8.5 Hz,
2H, ArH).
Br
K2CO3
DMSO
K2CO3
CO2H
Ar
Ar
Br
Br
1-Ethynyl-4-fluorobenzene (2f) 1H NMR (CDCl3,
500 MHz) δ: 3.03 (s, 1H, CH), 6.98—7.02 (m, 2H,
ArH), 7.41—7.49 (m, 2H, ArH).
1
2-
CO3
1-Chloro-4-ethynylbenzene (2g)
1H NMR
H
(CDCl3, 500 MHz) δ: 3.10 (s, 1H, CH), 7.28 (d, J=8.9
Ar
H
Ar
Hz, 2H, ArH), 7.40 (d, J=8.9 Hz, 2H, ArH).
2
1H NMR
Br
1-Chloro-2-ethynylbenzene (2h)
(CDCl3, 500 MHz) δ: 3.37 (s, 1H, CH), 7.21—7.28 (m,
2H, ArH), 7.39 (d, J=8.1 Hz, 1H, ArH), 7.52 (d, J=7.7
Hz, 1H, ArH).
E2 trans-elimination
1H NMR
Experimental section
2,4-Dichloro-1-ethynylbenzene (2i)
(CDCl3, 500 MHz) δ: 3.40 (s, 1H, CH), 7.20—7.22 (m,
General
1H, ArH), 7.42—7.46 (m, 2H, ArH).
1H NMR spectra were recorded using a Bruker
AM-500 spectrometer in CDCl3 with SiMe4 as an inter-
nal standard. Commercially obtained reagents were used
without further purification. Column chromatography
was carried out using a 300—400 mesh silica gel.
1-Bromo-4-ethynylbenzene (2j) 1H NMR (CDCl3,
500 MHz) δ: 3.12 (s, 1H, CH), 7.35 (d, J=8.6 Hz, 2H,
ArH), 7.46 (d, J=8.7 Hz, 2H, ArH).
1-Bromo-3-ethynylbenzene (2k)
1H NMR
(CDCl3, 500 MHz) δ: 3.12 (s, 1H, CH), 7.18 (t, J=7.9
Hz, 1H, ArH), 7.39—7.42 (m, 1H, ArH), 7.46—7.49 (m,
1H, ArH), 7.63—7.64 (m, 1H, ArH).
Synthesis of anti-3-aryl-2,3-dibromopropanoic (1)
anti-3-Aryl-2,3-dibromopropanoic acids (1a—1q)
were readily obtained by the bromination of corre-
sponding trans-α,β-unsaturated carboxylic acids in
CHCl3. The conditions were r.t. to 60 ℃ or irradiation
under a tungsten lamp.11
1-Bromo-2-ethynylbenzene (2l) 1H NMR (CDCl3,
500 MHz) δ: 3.38 (s, 1H, CH), 7.19 (t, J=7.7 Hz, 1H,
ArH), 7.26 (t, J=7.5 Hz, 1H, ArH), 7.52 (d, J=7.5 Hz,
1H, ArH), 7.58 (d, J=7.5 Hz, 1H, ArH).
Chin. J. Chem. 2011, 29, 2350— 2354
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2351