Organic Syntheses Procedure

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Org. Synth. 2000, 77, 249

DOI: 10.15227/orgsyn.077.0249

PHOTOCHEMICAL SYNTHESIS OF BICYCLO[1.1.1]PENTANE-1,3-DICARBOXYLIC ACID

Submitted by Michael D. Levin¹ , Piotr Kaszynski² , and Josef Michl¹ .

Checked by Michelle Pacholec and Steven Wolff.

1. Procedure

A. 1,3-Diacetylbicyclo[1.1.1]pentane (2). [1.1.1]Propellane is generated from 50 g (0.167 mol) of 1,1-dibromo-2,2-bis(chloromethyl)cyclopropane (Note 1) in pentane (Note 2) according to the procedure of Lynch and Dailey.³ To the solution of [1.1.1]propellane, 1 (Note 3), is added 15 mL of freshly distilled 2,3-butanedione and the mixture is irradiated with a 450 W medium pressure UV lamp (Ace Glass Co, catalog no. 7825-34) at −10 ± 5°C for 8 hr (Note 4). Solvents are evaporated on a rotary evaporator. The resulting crystalline material is washed three times with cold 2:1 pentane:diethyl ether to give 16.95 g of 1,3-diacetylbicyclo[1.1.1]pentane (2) (Note 5). Another 1 g of the diketone is obtained upon concentration and crystallization of the pentane/diethyl ether rinses. Thus the total yield of 2 is 17.95 g [70% from 1,1-dibromo-2,2-bis(chloromethyl)cyclopropane], mp 67.5-69°C (lit.⁴ mp, 67-69°C) (Note 6).

B. Bicyclo[1.1.1]pentane-1,3-dicarboxylic acid (3). A 1-L, three-necked, round-bottomed flask, equipped with a mechanical stirrer, addition funnel, and thermometer is charged with a solution of 43.3 g (1.08 mol) of sodium hydroxide in 315 mL of water and 25.5 mL (79.1 g, 0.495 mol) of bromine . The mixture is cooled to 0°C. A solution of the diketone (10 g, 0.066 mol) obtained in Part A in 36 mL of dioxane is added dropwise at such a rate that the temperature does not exceed 3°C (Note 7). After the addition is finished, the reaction mixture is stirred for 1 hr at 0°C, then overnight at room temperature. Sodium bisulfite (1.8 g) is added and the solution is extracted with chloroform (3 × 50 mL). Subsequently, 36 mL of concd hydrochloric acid is added to the aqueous layer. After the acidified solution is cooled to room temperature, the mixture is continuously extracted with diethyl ether for 50 hr (Note 8) in an extraction apparatus. Evaporation of ether from the extract yields 9.68 g (94.5% from diketone 2) of pure diacid 3, mp 302-305°C, with decomposition [lit.⁴ mp, 305°C (d)] (Note 9).

2. Notes

1. 1,1-Dibromo-2,2-bis(chloromethyl)cyclopropane was purchased from the Aldrich Chemical Company, Inc. It can be synthesized from 3-chloro-2-chloromethyl-1-propene, available from the Aldrich Chemical Company, Inc. , by phase-transfer dibromocyclopropanation.³^,⁵^,⁶

2. Pentane (98% grade) was obtained from Acros Organics and used without further purification.

3. The solution of [1.1.1]propellane should be warmed to −20-15°C to avoid crystallization of the 2,3-butanedione (which may not redissolve during the course of the irradiation).

4. It is recommended that the NMR spectrum of the reaction mixture be measured before discontinuing the irradiation. As long as any signal of [1.1.1]propellane (δ 2.0 ppm) is present, the irradiation should be continued.

5. The pentane-ether washes remove a yellow color from the crude product.

6. Spectral data were as follows: ¹H NMR δ: 2.14 (s, 6 H), 2.24 (s, 6 H) ; ¹³C NMR δ: 26.6, 43.3, 52.0, 205.6 ; IR (KBr) cm⁻¹: 1699 . MS 152 (1, M⁺), 137 (11), 109 (43), 95 (10), 43 (100), 39 (25) ; HRMS for C₉H₁₂O₂ calcd 152.0837, found 152.0835 . Anal. Calcd for C₉H₁₂O₂: C, 71.02; H, 7.95. Found: C, 71.01; H, 7.97.

7. Cooling of the reaction flask with an ice-salt or circulating bath held at −10°C helps to speed up the addition process.

8. Most of the product is extracted in the first 10 hr.

9. Spectral data were as follows: ¹³C NMR (acetone d₆) δ: 38.1, 53.0, 170.6 ; IR (KBr) cm⁻¹: 3017, 1698 . Anal. Calcd for C₉H₈O₄: C, 53.85; H, 5.16. Found: C, 53.43; H, 5.30.

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 procedure described above is an improved version of the one published by Kaszynski and Michl.⁴ [1.1.1]Propellane is a recently reviewed⁷ useful precursor for the synthesis of bicyclo[1.1.1]pentanes by radical addition across the central bond, followed by further transformations of the bridgehead substituents.⁴^,⁸ Under suitable conditions, one can obtain mixtures of [n]staffanes [oligomeric bicyclo[1.1.1]pentanes], which have been isolated in rapidly decreasing yields up to n = 5.⁵^,⁸ A review of their chemistry has appeared.⁹

References and Notes

Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215. We thank the National Science Foundation for generous financial support.
Present address: Department of Chemistry, Vanderbilt University, Nashville, TN 37235.
Mondanaro, K.; Dailey, W. P. Org. Synth. 1998, 75, 98. The submitters report an improved procedure (unchecked): Shtarev, A. B.; Pinkhassik, E.; Levin, M. D.; Stibor, I.; Michl, J. J. Am. Chem. Soc. 2001, 123, 3484 .
Kaszynski, P.; Michl, J. J. Org. Chem. 1988, 53, 4593.
Semmler, K.; Szeimies, G.; Belzner, J. J. Am. Chem. Soc. 1985, 107, 6410; Bunz, U.; Polborn, K.; Wagner, H. U.; Szeimies, G. Chem. Ber. 1988, 121, 1785; Della, E. W.; Taylor, D. K. J. Org. Chem. 1994, 59, 2986.
Kaszynski, P.; Friedli, A. C.; Michl, J. J. Am. Chem. Soc. 1992, 114, 601.
Kaszynski, P.; Michl, J. In "The Chemistry of the Cyclopropyl Group - Supplement"; Rappoport, Z., Ed.; John Wiley & Sons: Chichester, England, 1995, Vol. 2, p. 773-812.
Wiberg, K. B.; Waddell, S. T. J. Am. Chem. Soc. 1990, 112, 2194; Obeng, Y. S.; Laing, M. E.; Friedli, A. C.; Yang, H. C.; Wang, D.; Thulstrup, E. W.; Bard, A. J.; Michl, J. J. Am. Chem. Soc. 1992, 114, 9943.
Kaszynski, P.; Michl, J. Adv. Strain Org. Chem. 1995, 4, 283-331.

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

Bicyclo[1.1.1]pentane-1,3-dicarboxylic acid (9); (56842-95-6)

1,3-Diacetylbicyclo[1.1.1]pentane:
Ethanone, 1,1'-(bicyclo[1.1.1]pentane-1,3-diyl)bis- (12); (115913-30-9)

[1.1.1]Propellane:
Tricyclo[1.1.1.0^1,3]pentane (9); (35634-10-7)

1,1-Dibromo-2,2-bis(chloromethyl)cyclopropane:
Cyclopropane, 1,1-dibromo-2,2-bis(chloromethyl)- (11); (98577-44-7)

2,3-Butanedione (9); (431-03-8)

Bromine (8,9); (7726-95-6)

3-Chloro-2-(chloromethyl)-1-propene:
1-Propene, 3-chloro-2-(chloromethyl)- (8,9); (1871-57-4)

Notes

References/EndNotes

Article Compounds

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