Organic Syntheses Procedure

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Org. Synth. 1998, 75, 195

DOI: 10.15227/orgsyn.075.0195

3-CYCLOPENTENE-1-CARBOXYLIC ACID

Submitted by Jean-Pierre Deprés and Andrew E. Greene¹ .

Checked by Tammy J. Clark and Robert K. Boeckman, Jr..

1. Procedure

Caution! These transformations should be carried out in an efficient hood.

A. 3-Cyclopentene-1,1-dicarboxylic acid . A dry, 1-L, two-necked, round-bottomed flask (Note 1), equipped with a Teflon-covered magnetic stirring bar, is charged under a current of nitrogen with 33.0 g (0.250 mol) of dimethyl malonate , 50 mL of dry N,N'-dimethylpropyleneurea, DMPU, and 450 mL of dry tetrahydrofuran, THF (Note 2). The resulting solution is cooled by means of an ice bath and treated with 5.00 g (0.629 mol) of lithium hydride powder in one portion (Note 3). The nitrogen flow is discontinued, and the flask is capped with rubber septa and connected to a Nujol-filled bubbler by means of a syringe needle. After 15 min, the cooling bath is removed and stirring is continued until hydrogen evolution is complete (ca. 2 hr), whereupon 28.4 mL (0.269 mol) of cis-1,4-dichloro-2-butene (Note 4) is rapidly added by syringe. The mixture is heated by means of an oil bath at 40-45°C for 24 hr (Note 5). After the mixture is cooled to 20°C, 50 mL of water is added dropwise followed by 31.5 g (0.750 mol) of solid lithium hydroxide monohydrate . After the reaction mixture is stirred at 20°C for an additional 24 hr, it is treated with 350 mL of water, stirred for 10 min, and then transferred to a 2-L separatory funnel. Neutral material is removed by extraction with five 500-mL portions of ethyl acetate , each of which is back-washed with 30 mL of aqueous saturated sodium chloride solution. The combined aqueous phases are then acidified with 160 mL of 6 N hydrochloric acid , and extracted three times with 500-mL portions of ethyl acetate . The ethyl acetate extracts are combined, washed three times with 100 mL of 3 N hydrochloric acid and twice with 50 mL of aqueous saturated sodium chloride solution, dried over sodium sulfate , filtered, and concentrated by rotary evaporation. After removal of traces of solvent under high vacuum (1 hr at 0.1 mm), 35.8 g (92%) of 3-cyclopentene-1,1-dicarboxylic acid is obtained as an off-white solid, mp 163-165°C (Note 6).

B. 3-Cyclopentene-1-carboxylic acid . A 250-mL, one-necked, round-bottomed flask is charged with 35.8 g of 3-cyclopentene-1,1-dicarboxylic acid and then fitted with a reflux condenser capped with a rubber septum and connected to a Nujol-filled bubbler by means of a syringe needle. The contents of the flask are heated in an oil bath at 170-175°C until carbon dioxide evolution is complete (ca. 2 hr) and then allowed to cool to room temperature. The resulting oil is transferred to a 50-mL flask and vacuum distilled without fractionation to provide 23.0 g (89% or 82% overall from dimethyl malonate) of 3-cyclopentene-1-carboxylic acid as a clear, colorless oil, bp 88°C (2 mm) (Note 7).

2. Notes

1. All glassware was oven-dried and allowed to cool in a desiccator before use.

2. Dimethyl malonate (98%) was obtained from Fluka Chemical Corp. , and DMPU was purchased from Aldrich Chemical Company, Inc. DMPU was distilled from calcium hydride under reduced pressure and tetrahydrofuran was distilled from the sodium ketyl of benzophenone prior to use. The checkers employed dimethyl malonate obtained from Aldrich Chemical Company, Inc.

3. Lithium hydride powder was obtained from Acros Organics . The checkers obtained lithium hydride from Aldrich Chemical Company, Inc.

4. cis-1,4-Dichloro-2-butene was either purchased from Aldrich Chemical Company, Inc. or prepared² from cis-2-butene-1,4-diol (Fluka Chemical Corp.). The checkers used cis-1,4-dichloro-2-butene obtained from Aldrich Chemical Company, Inc.

5. The submitters report that dimethyl 3-cyclopentene-1,1-dicarboxylate (with <1% of the vinyl isomer)²^,³ can be isolated at this stage in 92% yield and then transformed to methyl 3-cyclopentene-1-carboxylate ⁴ with lithium chloride in wet dimethyl sulfoxide (DMSO)⁵ in 85% yield.

6. The checkers obtained a yield of 99% for the diacid, mp 160-163°C. Melting points of 164-169°C,² 170-172°C,² and 162-165°C ³ have been reported for this compound. The diacid has the following spectral properties: IR (Nujol) cm⁻¹: 3067, 1698, 1623 ; ¹H NMR [CDCl₃-CD₃COCD₃ (8:2), 300 MHz] δ: 3.08 [s(br), 4 H], 5.63 [s(br), 2 H], 10.90 [s(br), 2 H] ; ¹³C NMR [CDCl₃-CD₃COCD₃ (8:2), 75 MHz] δ: 46.5, 64.3, 133.1, 178.5 .

7. The checkers obtained yields of 91-93% for the acid, bp 81-83°C (1.7 mm). Distillation temperatures of 83-84°C (2 mm)²and 70°C (1 mm)³ have been reported for this compound. The acid has the following spectral properties: IR cm⁻¹: 3060, 1707, 1623 ; ¹H NMR (CDCl₃, 300 MHz) δ: 2.70 (m, 4 H), 3.12-3.25 (m, 1 H), 5.68 [s(br), 2 H], 11.96 [s(br), 1 H] ; ¹³C NMR (CDCl₃, 75 MHz) δ: 36.2, 41.5, 129.2, 182.5 .

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

The preparation described here of 3-cyclopentene-1-carboxylic acid from dimethyl malonate and cis-1,4-dichloro-2-butene is an optimized version of a method reported earlier³ for obtaining this often used and versatile building block.⁶ The procedure is simple and efficient and requires only standard laboratory equipment. 3-Cyclopentene-1-carboxylic acid has previously been prepared through reaction of diethyl malonate with cis-1,4-dichloro(or dibromo)-2-butene in the presence of ethanolic sodium ethoxide, followed by hydrolysis of the isolated diethyl 3-cyclopentene-1,1-dicarboxylate intermediate, fractional recrystallization of the resultant diacid to remove the unwanted vinylcyclopropyl isomer, and finally decarboxylation.²^,⁷ Alternatively, this compound can be obtained from the vinylcyclopropyl isomer (prepared from diethyl malonate and trans-1,4-dichloro-2-butene)⁸ or from cyclopentadiene ⁹ or cyclopentene.¹⁰ In comparison with the present procedure, however, all these methods suffer from poor selectivity, low yields, length, or need of special equipment or reagents, if not a combination of these drawbacks.

References and Notes

LEDSS, Chimie Recherche, Université Joseph Fourier, BP 53, 38041 Grenoble Cédex 9, France.
Murdock, K. C.; Angier, R. B. J. Org. Chem. 1962, 27, 2395-2398.
Deprés, J.-P.; Greene, A. E. J. Org. Chem. 1984, 49, 928-931.
Bond, F. T.; Ho, C-Y. J. Org. Chem. 1976, 41, 1421-1425.
Krapcho, A. P.; Lovey, A. J. Tetrahedron Lett. 1973, 957-961.
For selected recent examples, see: Banwell, M.; Edwards, A.; Harvey, J.; Hockless, D.; Willis, A. J. Chem. Soc., Perkin Trans. I 2000, 2175; Stafford, J. A.; Gonzales, S. S.; Barrett, D. G.; Suh, E. M.; Feldman, P. L. J. Org. Chem. 1998, 63, 10040; Hodgson, D. M.; Witherington, J.; Moloney, B. A. J. Chem. Soc., Perkin Trans. I 1994, 3373-3378; Norman, M. H.; Almond, M. R.; Reitter, B. E.; Rahim, S. G. Synth. Commun. 1992, 22, 3197-3204; Herndon, J. W.; Wu, C.; Harp, J. J. Organometallics 1990, 9, 3157-3171; McMurry, J. E.; Dushin, R. G. J. Am. Chem. Soc. 1990, 112, 6942-6949; Pauls, H. W.; Krantz, A. Synthesis 1989, 50-51; Hutchison, A.; Grim, M.; Chen, J. J. Heterocycl. Chem. 1989, 26, 451-452; Jacobson, K. A.; De La Cruz, R.; Schulick, R.; Kiriasis, L.; Padgett, W.; Pfleiderer, W.; Kirk, K. L.; Neumeyer, J. L.; Daly, J. W. Biochem. Pharmacol. 1988, 37, 3653-3661; Paquette, L. A.; Lin, H-S.; Gunn, B. P.; Coghlan, M. J. J. Am. Chem. Soc. 1988, 110, 5818-5826; Deshpande, M. N.; Wehrli, S.; Jawdosiuk, M.; Guy, Jr., J. T.; Bennett, D. W.; Cook, J. M.; Depp, M. R.; Weiss, U. J. Org. Chem. 1986, 51, 2436-2444. For several earlier references, see ref. ³
Meinwald, J.; Gassman, P. G.; Crandall, J. K. J. Org. Chem. 1962, 27, 3366-3368.
Schmid, G. H.; Wolkoff, A. W. J. Org. Chem. 1967, 32, 254.
Cremer, S. E.; Blankenship, C. J. Org. Chem. 1982, 47, 1626-1632.
Hoberg, H.; Ballesteros, A.; Sigan, A.; Jegat, C.; Milchereit, A. Synthesis 1991, 395-398.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

3-Cyclopentene-1-carboxylic acid (8,9); (7686-77-3)

3-Cyclopentene-1,1-dicarboxylic acid (11); (88326-51-6)

Dimethyl malonate:
Malonic acid, dimethyl ester (8);
Propanedioic acid, dimethyl ester (9); (108-59-8)

N,N'-Dimethylpropyleneurea [DMPU]:
2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- (8,9); (7226-23-5)

Lithium hydride (8,9); (7580-67-8)

cis-1,4-Dichlorobut-2-ene:
2-Butene, 1,4-dichloro-, (Z)- (8,9); (1476-11-5)

Lithium hydroxide monohydrate (8);
Lithium hydroxide, monohydrate (9); (1310-66-3)

Notes

References/EndNotes

Article Compounds

Authors