Checked by Qingzhi Gao and Hisashi Yamamoto.
1. Procedure
Ethyl (2Z)-3-bromopropenoate. To a
three-necked, round-bottomed flask are added
lithium bromide (10.0 g, 0.115 mol, (Note 1)),
acetonitrile (100 mL, (Note 2)),
acetic acid (7.0 g, 0.116 mol, (Note 3)), and
ethyl 2-propynoate (9.0 g, 0.092 mol, (Note 4), (Note 5)) under
nitrogen. The reaction is carried out with magnetic stirring under reflux and monitored by GLC (Note
6). The reaction is complete after 24 hr. The reaction is cooled, water (20 mL) is added to the flask, and the mixture is cautiously neutralized with solid
potassium carbonate, added in portions (Note
3). The organic layer is separated, and the aqueous layer is extracted with
ether (3 × 20 mL) (Note
3). The combined organic layers are dried with
magnesium sulfate and filtered. After removal of the solvent,
ethyl (2Z)-3-bromopropenoate is obtained by vacuum distillation (
14.0 g, yield,
85%, (Note
7)).
2. Notes
4. The optimum ratio of starting materials for this reaction is
LiBr : CH3CO2H : 2-propynoate = 1.25 : 1.25 : 1.
6. GLC was performed on a 2-m column (10% OV-1 supported on 102 silanized white support, 60–80 mesh) at 90°C.
7.
Ethyl (2Z)-bromopropenoate boils at
92–93°C/40 mm. Isomerization was not detected during careful distillation (bath temperature: <115°C). The spectral data are as follows: IR (neat) cm
−1: 1730, 1605, 1200, 1185; MS m/e: 181 [M
+(
81Br)+1]/179 [M
+(
79Br)+1]:
1H NMR (200 MHz, CDCl
3) δ: 1.31 (t, 3 H, J = 7.0), 4.24 (q, 2 H, J = 6.2), 6.61 (d, 1 H, J = 8.4), 6.99 (d, 1 H, J = 8.4). No E isomer was detected by
1H NMR, GLC (Note
6), or TLC on
silica gel (eluent:
petroleum ether : CH3CO2Et = 10:1).
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
3-Halopropenoic acids and their derivatives are valuable intermediates in organic synthesis because three functional groups are present: the C-X bond, the conjugated C=C bond, and the carbonyl group. These compounds can be used to react with nucleophiles,
2 and, as vinyl halides, to introduce a cis olefinic moiety into an organic molecule using organometallic methods, for the synthesis of (2Z)-en-4-ynoic and (2Z,4Z)- and (2Z,4E)-dienoic acid derivatives.
3 Usually such compounds are prepared as a Z and E isomeric mixture. Only a few stereoselective synthetic methods have been reported, most of which are for E isomers. For example, the title compound was reported to be prepared as a Z and E isomeric mixture via the reaction of
ethyl 2-propynoate with
hydrogen bromide in
acetic acid.
4 The only possible route for its synthesis is by esterification of
(2Z)-3-bromopropenoic acid5 according to the method for
methyl (2Z)-3-chloropropenoate, but isomerization may occur during the prolonged heating of esterification.
6 No one-step method for the synthesis of the pure Z isomer is available. The stereospecific method described here can also be applied to the synthesis of (2Z)-3-halopropenoic acids,
7,8 (2Z)-3-halopropenoates,
7,8,9 (2Z)-3-halo-propenamides,
8 and (2Z)-3-halopropenenitriles
8 (X=I, Br, Cl). In the case of the iodide,
sodium iodide and
lithium iodide gave similar results, but it is necessary to carry out the reaction under N
2.
9 With the bromide and chloride, lithium salts gave higher yields than sodium salts. The mechanism of this reaction is believed to involve nucleophilic addition of halide anion to the electron-deficient, carbon-carbon triple bond. The stability of a termolecular transition state or stereoelectronic stabilization of the anion intermediate formed in situ by the nucleophilic addition might be responsible for the high stereospecificity.
8
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