Org. Synth. 1997, 74, 212
DOI: 10.15227/orgsyn.074.0212
PREPARATION OF 3-BROMOPROPIOLIC ESTERS:METHYL AND tert-BUTYL 3-BROMOPROPIOLATES
[2-Propynoic acid, 3-bromo-, methyl and 1,1-dimethylethyl esters]
Checked by Paul N. Devine and Ichiro Shinkai.
1. Procedure
CAUTION! Propiolates and their bromo derivatives are lachrymators and must be handled under an efficient hood. Distillation of bromopropiolates should be carried out behind a safety shield (Note 1).
Methyl 3-bromopropiolate. A 250-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar is charged with 100 mL of acetone (Note 2) and 4.0 g (47.6 mmol) of methyl propiolate (Note 3). To the stirred solution at room temperature is added 0.8 g (4.7 mmol) of silver nitrate. After 5 min, 9.8 g of N-bromosuccinimide (55 mmol) is added at once. The homogeneous mixture becomes cloudy and a grayish precipitate develops. Stirring is continued for 2 hr (Note 4). The solids are filtered through a pad of Celite, which is rinsed with acetone (30–50 mL). After careful rotary evaporation of the acetone at ≈20°C under 20 mm, the oily residue is bulb-to-bulb distilled at room temperature under reduced pressure (≈0.1 mm), affording methyl 3-bromopropiolate as a colorless liquid (7.0–7.5 g, 42.9–46.0 mmol, 90–97%) solidifying in the refrigerator (mp ≈20°C) (Note 5).
tert-Butyl 3-bromopropiolate. tert-Butyl propiolate (Note 6) (5.42 g, 42.8 mmol) dissolved in 150 mL of acetone is treated as above with 0.8 g of silver nitrate (4.7 mmol) and, after 5 min of stirring at room temperature, with 9.8 g (55 mmol) of N-bromosuccinimide introduced at once into the suspension. Stirring is continued for 90 min. The solids are filtered through a pad of Celite, rinsed with acetone (30–50 mL) and the filtrate is concentrated at 20–25°C (20 mm) to give a white pasty solid. Water (80 mL) is added and the mixture is extracted with ether (3 × 80 mL). The ethereal layer is dried over anhydrous magnesium sulfate and the solvent is evaporated, leaving a semi-solid residue which is bulb-to-bulb distilled in an oil-bath at 45–50°C (≈0.1 mm) to give tert-butyl 3-bromopropiolate as a white semi-solid (8.51 g, 41.5 mmol, 97%) (Note 7).
2. Notes
1.
Explosions during distillation of certain bromoalkynes have been reported.
2 Although
methyl 3-bromopropiolate was not specifically cited, precautionary measures are recommended. The tert-butyl ester is a new compound
3 and must be handled like the methyl ester.
2.
Acetone may be redistilled before use to remove the eventual autocondensation product,
4-hydroxy-4-methyl-2-pentanone (diacetone alcohol, bp 166°C). The submitter used, as received, fresh
99% pure acetone from Prolabo.
3.
Methyl propiolate 99%, N-bromosuccinimide 99%, and silver nitrate were obtained from Janssen Chimica and used as received.
4.
One hour of stirring is usually sufficient for completion of the reaction, but this time can be exceeded; longer reaction times improve the succinimide particle size, which aids the subsequent filtration. The product seems to adhere to the succinimide.
5.
Depending on the conditions of the preliminary evaporation this product is contaminated with up to 5% of residual
acetone. Nevertheless, it can be considered as pure enough for certain uses. Complete removal of
acetone may be obtained by distillation in a
small Vigreux column, although a yellowing of the distillate is observed: bp
86–88°C/100 mm (lit.
2 88°C/100 mm and lit.
4 40–45°C/5 mm). The spectral and analytical properties of
methyl 3-bromopropiolate are as follows:
1H NMR (200 MHz, CDCl
3) d: 3.73 (s, CH
3);
13C NMR (50 MHz, CDCl
3) δ: 52.8 (C-3), 52.9 (CH
3), 72.4 (C-2), 152.8 (C-1). Anal. Calcd for C
4H
3BrO
2 (undistilled sample): C, 29.48; H, 1.86; Br, 49.03. Found: C, 29.11; H, 1.92; Br 48.79.
6.
tert-Butyl propiolate was prepared from
propiolic acid and
isobutene in the presence of
sulfuric acid.
5 It is now commercially available from Fluka Chemical Corp. and Aldrich Chemical Company, Inc.
7.
Although pure enough to be used as obtained,
tert-butyl 3-bromopropiolate may be distilled in a Vigreux column at
75–77°C (15 mm) to give a colorless oil crystallizing as plates: mp
25–27°C. The spectral and analytical properties of
tert-butyl 3-bromopropiolate are as follows:
1H NMR (200 MHz, CDCl
3) δ: 1.46 (s, CH
3);
13C NMR (50 MHz, CDCl
3) δ: 27.8 (CH
3), 50.0 (C-3), 73.9 (C-2), 84.0 (CMe
3), 151.3 (C-1). Anal. Calcd for C
7H
9BrO
2 (undistilled sample): C, 41.00; H, 4.42; Br, 38.48. Found: C, 40.48, H, 4.40; Br, 38.10.
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.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
Methyl 3-bromopropiolate has been prepared by esterification of
3-bromopropiolic acid with
methanol and
sulfuric acid for 6 days (
75% yield),
4 the starting bromo acid being prepared by bromination of
propiolic acid with aqueous
potassium hypobromite.
6 This reaction is particularly delicate to control, giving erratic results. Moreover, direct bromination of
methyl propiolate with
sodium hypobromite2 could not be reproduced.
Bromination of 1-alkynes with
N-bromosuccinimide in the presence of catalytic amounts of
silver nitrate, was used first for the bromination of 17-ethynyl steroids.
7 Similarly,
N-iodosuccinimide led to 17-iodoethynyl steroids. Iodination of propiolates in this way has not been studied. A recent method of preparation of 1-iodoalk-1-ynes under phase-transfer conditions involves molecular
iodine and
copper(I) iodide as catalyst, in the presence of
potassium or sodium carbonate as a base.
Ethyl 3-iodopropiolate was prepared by this route in
80% yield.
8The present procedure provides ready access to 3-bromopropiolic esters, the methyl ester requiring adapted work up, because of its low boiling point. Less volatile esters, like tert-butyl, can be conveniently isolated by a standard aqueous-extraction work up.
Methyl 3-bromopropiolate has been used in Diels-Alder reactions either as a methoxycarbonyl ketene equivalent
9 10 or for the synthesis of functionalized naphthalenes.
11
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
METHYL AND tert-BUTYL 3-BROMOPROPIOLATES
potassium carbonate (584-08-7)
sulfuric acid (7664-93-9)
methanol (67-56-1)
ether (60-29-7)
silver nitrate (7761-88-8)
sodium carbonate (497-19-8)
iodine (7553-56-2)
acetone (67-64-1)
4-hydroxy-4-methyl-2-pentanone (123-42-2)
sodium hypobromite
copper(I) iodide (7681-65-4)
magnesium sulfate (7487-88-9)
isobutene (9003-27-4)
potassium hypobromite
N-bromosuccinimide (128-08-5)
methyl propiolate (922-67-8)
N-Iodosuccinimide (516-12-1)
propiolic acid (471-25-0)
Methyl 3-bromopropiolate,
2-Propynoic acid, 3-bromo-, methyl ester (23680-40-2)
tert-Butyl propiolate (13831-03-3)
tert-Butyl 3-bromopropiolate,
2-Propynoic acid, 3-bromo-, 1,1-dimethylethyl ester
3-bromopropiolic acid
Ethyl 3-iodopropiolate
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved