A Publication of Reliable Methods for the Preparation of Organic Compounds Working with Hazardous Chemicals The procedures in Organic Syntheses are intended for use only by persons with proper 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; the full text can be accessed free of charge at http://www.nap.edu/catalog.php?record_id=12654). 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. In some articles in Organic Syntheses, chemical-specific hazards are highlighted in red “Caution Notes” within a procedure. It is important to recognize that the absence of a caution note does not imply that no significant hazards are associated with the chemicals involved in that procedure. Prior to performing a reaction, a thorough risk assessment should be carried out that includes a review of the potential hazards associated with each chemical and experimental operation on the scale that is planned for the procedure. Guidelines for carrying out a risk assessment and for analyzing the hazards associated with chemicals can be found in Chapter 4 of Prudent Practices. The procedures described in Organic Syntheses are provided as published and are 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. September 2014: The paragraphs above replace the section “Handling and Disposal of Hazardous Chemicals” in the originally published version of this article. The statements above do not supersede any specific hazard caution notes and safety instructions included in the procedure. DOI:10.15227/orgsyn.070.0177 Organic Syntheses, Coll. Vol. 9, p.372 (1998); Vol. 70, p.177 (1992). CYCLOPROPANATION USING AN IRON-CONTAINING METHYLENE TRANSFER REAGENT: 1,1- DIPHENYLCYCLOPROPANE [Iron (1+), dicarbonyl(η5-2,4-cyclopentadien-1-yl)(dimethylsulfonium η- methylide)-, tetrafluoroborate (1-) and Benzene, 1,1'-cyclopropylidenebis-] Submitted by Matthew N. Mattson1, Edward J. O'Connor2, and Paul Helquist1. Checked by Jörn-Bernd Pannek and Ekkehard Winterfeldt. 1. Procedure CAUTION! This experiment should be performed in an efficient fume hood because of the unpleasant odors of sulfide-containing materials. In addition, the first part of this procedure should be conducted behind a safety shield because of the use of highly reactive sodium metal. Into a dry, one-necked, 2000-mL, round-bottomed flask is placed a medium-sized magnetic stirring bar (Note 1) and cyclopentadienyliron dicarbonyl dimer [C5H5(CO)2Fe]2, (0.50 mol equiv, 0.21 mol, 74.4 g; (Note 2) and (Note 3)). Sodium dispersion (40% by weight) in light mineral oil (1.25 mol equiv, 0.52 mol, 30.1 g; (Note 4) and (Note 5)) is weighed into the flask (Note 6). The flask is then equipped with a reflux condenser topped with a three-way stopcock (Note 7) having a vertical tubulation capped with a septum through which solvents and reagents can be introduced with long needles or cannulas. By evacuation through the other tubulation of the stopcock, the apparatus is evacuated and filled with nitrogen twice, then placed under vacuum (≤0.1 mm) for 1 to 2 hr to remove the bulk of the mineral oil. The flask is filled with nitrogen, and tetrahydrofuran (THF; 850 mL; (Note 8)) is transferred into the flask. Rapid stirring is begun and maintained while an oil bath or a heating mantle is employed to heat the mixture at reflux for ≥ 18 hr. The flask is cooled to 0°C in an ice bath, and chloromethyl methyl sulfide (1.00 mol equiv, 0.42 mol, 35.2 ml) is added dropwise with a syringe over 25 min (Note 9) and (Note 10). After residues of the sulfide are rinsed into the flask with additional THF (ca. 5–10 mL), the mixture is stirred at 0°C for 1 hr and then at 25°C for 1 hr (Note 11). Iodomethane (1.30 mol equiv, 0.55 mol, 34.0 mL; (Note 12)) is added over 5 min using a syringe. After residues of iodomethane are rinsed into the flask with THF (5– 10 mL), the mixture is stirred at 25°C for ≥ 15 hr. Stirring is stopped (Note 13), and the volatile materials are removed under vacuum (≤0.1 mm) using a large, liquid nitrogen-cooled trap (Note 14). The vacuum in the apparatus is relieved with nitrogen, and the three-way stopcock is removed from the top of the condenser, exposing the reaction mixture to air. In a 2000-mL Erlenmeyer flask containing a magnetic stirring bar, a solution of sodium tetrafluoroborate (6.00 mol equiv, 2.52 mol, 277 g) in water (1200 mL total volume of solution) is prepared and heated to 95°C while being stirred. A 1000-mL portion of the hot sodium tetrafluoroborate solution solution is slowly poured down the condenser into the reaction mixture which is kept at ca. 95°C while being stirred. At the same time, a 350-mL, medium-frit, sintered-glass Büchner funnel is prepared with a 2.5-cm layer of diatomaceous earth and a 1-cm layer of sand covered with a piece of filter paper with holes punched in it, and the funnel is preheated by passage, with suction, of 700–1000 mL of hot, distilled water which is then discarded. The condenser is removed from the reaction flask, and the contents are suction-filtered through the hot funnel into a heated, 2000-mL filter flask (Note 15). The remaining hot sodium tetrafluoroborate solution is used to rinse the reaction flask and the hot funnel. The combined filtrates are swirled while being cooled. If necessary, a seed crystal can be added. The filtration flask is placed in an ice bath while swirling is continued. After the temperature reaches 0°C, the flask is placed in a freezer at ca. −10°C for 1–3 hr. The product is collected by suction filtration using a large, chilled Büchner funnel (Whatman no. 1 filter paper) and is rinsed with ice-cold distilled water (150 mL) and cold diethyl ether (1500 mL). The filter cake is broken up, and the crystals are dried in a stream of air overnight. There is obtained 100.6 g (70.4%) of (η5- + − C5H5)(CO)2FeCH2S (CH3)2 BF4 as free-flowing, flake-like, amber crystals (Note 16),(Note 17),(Note 18). The yields were found to be considerably lower on runs of smaller scale (Note 19). Into a 200-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar are placed the crystalline reagent (35 g, 0.10 mol; (Note 20)), 1,1-diphenylethene (9.1 mL, 9.3 g, 0.05 mol; (Note 21)), and dioxane (25 mL; (Note 22) and (Note 23)). The flask is equipped with a reflux condenser topped with a stopcock, and a nitrogen atmosphere (Note 24) is established within the apparatus. While being stirred vigorously, the heterogeneous mixture is heated to reflux in an oil bath (120°C) for 14 hr (Note 25). The brown mixture is removed from the oil bath and allowed to cool sufficiently to permit the addition of hexane (75 mL, (Note 26)) to the flask. The mixture is stirred in the air until the flask reaches 25°C. The supernatant liquid containing the product is poured from the flask and filtered through Whatman no. 1 filter paper. The remaining solid is repeatedly suspended and washed with several portions of hexane (ca. 1000 mL total; (Note 27)). The combined filtrates are filtered through a pad of silica gel in a sintered glass Büchner funnel and are then concentrated by rotary evaporation. The residual dark brown oil is dissolved in methanol (200 mL) to give an orange-brown solution which immediately becomes dark green when solid ferric chloride (7 g; (Note 28)) is added at 25°C. The mixture is stirred for 15 min and then concentrated by rotary evaporation. The residual dark green oil is extracted with two 200-mL portions of hexane, and the combined extracts are filtered through a pad of silica gel and concentrated by rotary evaporation. The colorless oil that remains is distilled through a short-path apparatus to give 8.76 g (88%) of 1,1-diphenylcyclopropane as a clear, colorless liquid, bp 89°C (0.8 mm; lit3 110–111°C, 1.3 mm; (Note 29)). The checkers obtained 65–77% yield of product on roughly half the scale. 2. Notes 1. The stirring bar must be able to stir the heterogeneous reaction mixture rapidly. Very good stirring is required for the metallic sodium dispersion to react efficiently. A medium-sized, egg-shaped stirring bar (32 × 16 mm, available from Fisher Scientific Company) was found to be particularly effective. 2. Cyclopentadienyliron dicarbonyl dimer [C5H5(CO)2Fe]2 can be purchased from Alfa Products, Morton/Thiokol Inc. or Aldrich Chemical Company, Inc. Alternatively, it is easily and inexpensively prepared by heating dicyclopentadiene with iron pentacarbonyl. Our yield (80–90%) of this reagent is considerably higher than that reported in the literature procedure.4 3. In order to allow for proper placement of the sodium dispersion in the flask later (Note 5), the [C5H5 (CO)2Fe]2 was neatly piled in a mound on top of the stirring bar in the middle of the bottom of the flask.