Org. Synth. 1995, 72, 112
DOI: 10.15227/orgsyn.072.0112
STEREOSPECIFIC SYNTHESIS OF ETHYL (Z)-3-BROMO-2-PROPENOATE
[2-Propenoic acid, 3-bromo-, ethyl ester, (Z)-]
Submitted by Shengming Ma and Xiyan Lu
1.
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
1.
Lithium bromide (reagent grade) was dried over
phosphorus pentoxide (P2O5) with heating at 100°C under vacuum.
2.
Acetonitrile was distilled from
P2O5 before use.
3.
Acetic acid, potassium carbonate and ether are reagent grade.
4.
The optimum ratio of starting materials for this reaction is
LiBr : CH3CO2H : 2-propynoate = 1.25 : 1.25 : 1.
5.
Ethyl 2-propynoate is available from Aldrich Chemical Company, Inc.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).
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
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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.
8This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
silica gel
petroleum ether
P2O5
LiBr
CH3CO2H
CH3CO2Et
potassium carbonate (584-08-7)
acetic acid (64-19-7)
ether (60-29-7)
acetonitrile (75-05-8)
hydrogen bromide (10035-10-6)
nitrogen (7727-37-9)
sodium iodide (7681-82-5)
magnesium sulfate (7487-88-9)
ethyl 2-propynoate (623-47-2)
lithium iodide (10377-51-2)
lithium bromide (7550-35-8)
phosphorus pentoxide (1314-56-3)
2-propynoate
Ethyl (2Z)-3-bromopropenoate,
ETHYL (Z)-3-BROMO-2-PROPENOATE,
2-Propenoic acid, 3-bromo-, ethyl ester, (Z)- (31930-34-4)
Ethyl (2Z)-bromopropenoate
(2Z)-3-bromopropenoic acid (1609-92-3)
methyl (2Z)-3-chloropropenoate
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