Org. Synth. 1990, 69, 148
DOI: 10.15227/orgsyn.069.0148
METHYL 2-CHLORO-2-CYCLOPROPYLIDENACETATE
[Acetic acid, chlorocyclopropylidene-, methyl ester]
Submitted by Thomas Liese, Fereydoun Seyed-Mahdavi, and Armin de Meijere
1.
Checked by James S. Piecara and Bruce E. Smart.
1. Procedure
A. Trimethyl 2-chloro-2-cyclopropylidenorthoacetate. A 1-L, two-necked, round-bottomed flask equipped with a mechanical stirrer and a reflux condenser is charged with 40.0 g (0.19 mol) of 1-chloro-1-(trichloroethenyl)cyclopropane (Note 1), 120 g of potassium hydroxide, and 300 mL of methanol (Note 2). The mixture is stirred for 16–18 hr in an oil bath at 85°C. After the solution is cooled to room temperature, it is diluted with 1 L of ice water. The mixture is then transferred to a 3-L separatory funnel and extracted with three 200-mL portions of ether. The combined ether phases are washed with three 150-mL portions of saturated brine, dried over anhydrous magnesium sulfate, and filtered. The solvent is removed from the filtrate by distillation at atmospheric pressure, and the residue is distilled through a short-path column under water-aspirator vacuum to give 14.5–15.4 g (39–41%) of trimethyl 2-chloro-2-cyclopylidenorthoacetate bp 103–105°C (20 mm) (Note 3) and (Note 4).
B. Methyl 2-chloro-2-cyclopropylidenacetate. A 250-mL, one-necked, round-bottomed flask is charged with 60 mL of methylene chloride (Note 2), 3.5 g of a strongly acidic ion-exchange resin (Note 5), and 11.0 g (0.057 mol) of trimethyl 2-chloro-2-cyclopropylidenorthoacetate. The mixture is stirred for 12 hr at room temperature. The ion-exchange resin is removed by filtration and washed with three 10-mL portions of methylene chloride. The combined organic solutions are dried over anhydrous magnesium sulfate, filtered, and distilled at atmospheric pressure to remove the solvent. The residue is distilled through a short-path column under reduced pressure to give 6.2–6.7 g (74–80%) of methyl 2-chloro-2-cyclopropylidenacetate, bp 95–97°C (10 mm) (Note 6),(Note 7)(Note 8).
2. Notes
2.
Methanol and methylene chloride were obtained from E. M. Science (Merck & Company, Inc.) and used without further purification.
3.
The checkers obtained the same yields for 0.10-mol scale runs. The submitters report yields of
54–58%, however. The submitters report that the yields of 2-chloro-2-cyclopropylidenacetate are consistently better, when a larger excess of
sodium methoxide (prepared by dissolving 20.1 g (0.87 mol) of sodium metal in 300 mL of dry methanol) is used. The reaction is monitored by thin layer chromatography; complete consumption of starting material may require up to 48 hr. The workup procedure was also modified. Instead of extracting with
ether, the mixture is extracted with three
100-mL portions of methylene chloride. The combined
methylene chloride extracts are washed with three
50-mL portions of saturated brine, dried over anhydrous
magnesium sulfate, and filtered. The solution is concentrated under slightly reduced pressure in a closed system (
rotary evaporator) to a volume of 100 mL. In Step B this solution is treated with 10 g of a strongly acidic ion-exchange resin and the rest of the procedure is followed as described.
4.
The submitters report bp
107–109°C (20 mm). The spectral properties of 2-chloro-2-cyclopropylidenorthoacetate are as follows: IR (neat) cm
−1: 2840 (OCH
3), 1780 (C=C);
1H NMR (CDCl
3) δ: 1.27–1.80 (m, 4 H), 3.23 (s, 9 H).
5.
The checkers used analytical-grade AG 50W-X8 resin, which is strongly acidic polystyrene-gel-type resin, supplied by Bio-Rad Laboratories. The submitters used the large-pore, strongly acidic ion-exchange resin Lewatit SPC 118, supplied by Bayer AG.
6.
The submitters report obtaining
7.0–7.5 g (
84–90%) of product, bp
60–63°C (3.7 mm), and note that
4.7–5.0 g of analytically pure material, mp
33–34°C, can be obtained by crystallization at −20°C from
10–15 mL of pentane and the remaining
2.3–2.5 g of product can be recovered from the mother liquor by chromatography on
silica gel (60 g) using a
5 : 1 mixture of pentane/diethyl ether as the eluent.
7.
The product obtained by the checkers is pure by NMR analysis and shows the following spectral properties: IR (neat) cm
−1: 3080 (cyclopropyl CH), 1720 (C=O);
1H NMR (CDCl
3) δ: 1.42–1.52 (m, 2 H), 1.69–1.78 (m, 2 H), 3.84 (s, 3 H).
8.
The submitters report that the product can be obtained in higher yields without isolation of the intermediate orthoester according to the following procedure. To a solution of
sodium methoxide, freshly prepared by dissolving 14.0 g (0.61 mol) of sodium metal in 200 mL of dry methanol, at 65°C is added with stirring
30.0 g of 1-chloro-1-(trichloroethenyl)cyclopropane. The stirred mixture is refluxed (oil-bath temperature of 110°C) for 72 hr. After the solution is cooled to room temperature, 200 mL of ice water is added, and the mixture is extracted with three
200-mL portions of ether. The combined
ether extracts are washed with three
50-mL portions of saturated brine, dried over anhydrous
magnesium sulfate, and filtered. The solvent is removed from the filtrate by distillation at atmospheric pressure. The residue is dissolved in
100 mL of methylene chloride, 10 g of a strongly acidic ion-exchange resin is added
(Note 5), and the mixture is stirred at room temperature for 48 hr. The resin is removed by filtration and is washed with three
10-mL portions of methylene chloride. The combined organic solutions are dried over anhydrous
magnesium sulfate and filtered, and the solvent is removed from the filtrate by distillation at atmospheric pressure. The residual oil is taken up in
200 mL of pentane and the solution is refrigerated at 5°C. The precipitated crystals are collected by filtration to yield
11–13 g (
51–60%) of 2-chloro-2-cyclopropylidenacetate. The checkers obtained a
50% yield of pure product, mp
40–41°C, when this procedure was repeated on about half the scale.
3. Discussion
This procedure is applicable to a number of substituted 1-chloro-1-(trichloroethenyl)cyclopropanes,
2 and in general gives good yields of methyl 2-chloro-2-cyclopropylidenacetates.
3 These are highly reactive Michael acceptors that react rapidly with nucleophiles to give 1'-substituted-2-chloro-2-cyclopropylacetates. The parent 2-chloro-2-cyclopropylidenacetate is a particularly useful building block in organic synthesis since it adds to cyclic dienolates to give complex skeletons in high yields.
4,5 In addition, it is a reactive dienophile
5,6 and can be further modified to 2-arylthio-substituted derivatives as well as to the parent
methyl 2-cyclopropylidenacetate in high yields.
7 The corresponding
ethyl 2-cyclopropylidenacetate has been prepared in poor yield by a Wittig–Horner–Emmons olefination of
cyclopropanone hemiacetal magnesium salt (
8%),
8 and more recently in vastly improved yield (
87%) by the benzoic-acid-catalyzed Wittig olefination.
9
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
silica gel
brine
trimethyl 2-chloro-2-cyclopylidenorthoacetate
cyclopropanone hemiacetal magnesium salt
methanol (67-56-1)
ether,
diethyl ether (60-29-7)
sodium methoxide (124-41-4)
potassium hydroxide (1310-58-3)
sodium (13966-32-0)
Pentane (109-66-0)
methylene chloride (75-09-2)
magnesium sulfate (7487-88-9)
tetrachlorocyclopropene
1-CHLORO-1-(TRICHLOROETHENYL)CYCLOPROPANE (82979-27-9)
Methyl 2-chloro-2-cyclopropylidenacetate,
Acetic acid, chlorocyclopropylidene-, methyl ester (82979-45-1)
Trimethyl 2-chloro-2-cyclopropylidenorthoacetate (82979-34-8)
methyl 2-cyclopropylidenacetate
ethyl 2-cyclopropylidenacetate
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