Checked by Jörn-Bernd Pannek and Ekkehard Winterfeldt.
1. Procedure
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; lit
3 110–111°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 [C
5H
5(CO)
2Fe]
2 was neatly piled in a mound on top of the stirring bar in the middle of the bottom of the flask.
4. The
40% (by weight) sodium dispersion in light mineral oil was used as obtained from Aldrich Chemical Company, Inc., except for thorough shaking immediately prior to transfer of the dispersion.
5. A
1-cm diameter glass tube narrowed to a tip at one end and equipped with a pipet bulb was used to transfer the dispersion which was carefully placed around the perimeter of the mound of [C
5H
5(CO)
2Fe]
2. After evaporation of the oil, the stirring bar should rest in the center of the ring of
sodium without contacting it. In this way, the reaction mixture can subsequently be stirred more efficiently. Also, all of the
sodium should lie below the surface of the
tetrahydrofuran solution formed, so that the mixture reacts efficiently upon being heated at reflux.
6. The procedure described here for reductive cleavage of this compound with
sodium dispersion
5 to give
sodium cyclopentadienyldicarbonylferrate is considerably more convenient and less hazardous than the more traditional use of
sodium amalgam that was reported previously.
6 7 8
7. The stopcock used in this procedure is of the design shown in
f.htmigure 1. A source of inert gas and vacuum can be attached to the horizontal tubulation. The vertical tubulation is capped with a septum to allow introduction of liquid reagents and solvents through use of a long syringe needle or cannula inserted through the septum and down through the body of the stopcock. In order to avoid air leaks through the septum into the reaction apparatus when reagents are not being added, the stopcock is normally turned to close off the vertical tubulation, but to leave the flask open to the nitrogen/vacuum source.
Figure 1
8. Commercial,
anhydrous-grade tetrahydrofuran (THF) is further purified by distillation from a dark blue or purple solution of
sodium benzophenone ketyl or dianion under
nitrogen. One method for transferring the THF into the reaction flask is through the use of cannulas. The cannulas (available from Aldrich Chemical Company, Inc.) are constructed from 60-cm sections of 18-gauge stainless steel tubing with a needle tip at each end. It is perhaps more convenient to use two short sections of needle tubing (each having a needle point at only one end) joined with 25–50 cm of small-diameter Teflon tubing. Transfer through the cannula is facilitated by applying a slight vacuum to the reaction apparatus while maintaining a positive pressure of
nitrogen in the flask originally containing the distilled THF. Alternatively, the THF can be distilled directly into the reaction flask.
9.
Chloromethyl methyl sulfide was obtained from Aldrich Chemical Company, Inc. and distilled under
nitrogen prior to use, although direct use of the commercial material without distillation had little effect on the overall efficiency of this procedure.
10.
WARNING: Chloromethyl methyl sulfide has a very unpleasant, penetrating odor and should be handled in a properly ventilated fume hood. Also, because of its structural similarity to
chloromethyl methyl ether which is highly toxic and an OSHA-regulated carcinogen, this sulfide should be handled as a substance having potentially similar toxic properties.
11. The product of this alkylation step is (η
5-C
5H
5)(CO)
2FeCH
2SCH
3 which is used directly in the next step but which, if desired, can be isolated as a dark yellow-brown, somewhat air-sensitive oil in greater than 90% yield.
9,10 11
12.
Iodomethane (99%) was used as obtained from Aldrich Chemical Company, Inc. Excess
iodomethane is used to quench any unreacted
sodium metal.
13. At this point, the flask can be swirled so that any small amounts of
sodium adhering to the wall of the flask above the solution level can be coated with the reaction mixture.
15. In order for this filtration to proceed smoothly, the funnel and its contents must remain hot to avoid premature crystallization of the product and clogging of the funnel. Minor clogging can be remedied by addition of a 100-mL portion of boiling distilled water to the funnel. Major clogging may require addition of boiling water and agitation of the filtration media with a
spatula. This addition, however, may reduce the yield of the crystallized product.
16. Physical data for this compound are the following: mp
129–130°C (corrected); IR (KBr pellet) cm
−1: 3120, 3035, 2040, 1955, 1417, 1328, 1280, 1055, 852;
1H NMR (80 MHz, CD
3NO
2) δ: 2.72 (s, 2 H, CH
2), 3.00 (s, 6 H, 2 CH
3), 5.34 (s, 5 H, C
5H
5);
13C NMR (20 MHz, CD
3NO
2) 13.35 (CH
2), 31.20 (CH
3), 87.88 (C
5H
5), 215.56 (CO).
17. This material is satisfactory for alkene cyclopropanation reactions, although recrystallization can be effected very easily by dissolving the crude product in
nitromethane at 25°C in the air and by slowly cooling the filtered solution to −70°C. The recrystallization recovery is greater than 80% and provides large, "gem-like," amber-colored crystals.
Acetone can also be used as the recrystallization solvent.
18. This reagent can be stored in ordinary flasks or bottles in the air, but it should be protected from bright light, which leads to slow decomposition. Storage in a dark brown bottle is recommended.
19. The checkers' yields ranged from
25–46% in preparations that were run on one-fourth to one-half of the scale used by the submitters.
20. A two-fold excess of the
iron reagent is employed to assure high conversion of the alkene to the
cyclopropane. Equimolar amounts of the starting materials can be used, but the
cyclopropane yield is ca. 20% lower.
21.
1,1-Diphenylethene is obtained from Aldrich Chemical Company, Inc. and is used without further purification.
23.
Nitromethane is also a good solvent for this reaction, and in some cases gives somewhat higher yields of cyclopropanes. Also, the reaction times are reduced to 2–4 hr when
nitromethane is used. Before use, this solvent is purified according to a published procedure.
12 Commercially obtained solvent is first dried over anhydrous
magnesium sulfate and then over anhydrous
calcium sulfate. The solvent is filtered into a flask containing activated 3 Å molecular sieves and is heated at 60°C for 8 hr while being stirred.
Nitromethane is distilled from the powdered molecular sieves under reduced pressure (bp
58°C, 150 mm; lit.
12 58°C, 160 mm) directly into a flask containing additional 3 Å molecular sieves. The purified solvent is stored in the dark. When "wet"
nitromethane from commercial sources is used directly as the reaction solvent, the percent conversions of alkenes to cyclopropanes are reduced substantially.
CAUTION: Distillations of
nitromethane and reactions using this solvent at elevated temperature should be conducted behind a safety shield.
24. When the cyclopropanation reactions are run in the presence of air, the yields are slightly reduced.
25. Vigorous stirring is necessary for a reasonable rate of reaction. The mixture remains heterogeneous both before and after the
iron reagent melts. Monitoring of the reaction by GLPC (2-m 5% OV-1 or SE-30) is recommended to assure maximum conversion before the reaction is stopped.
26. The function of the
hexane (or
pentane) is to promote precipitation of organometallic byproducts.
27. The solid is bright yellow after these washings and consists primarily of [C
5H
5(CO)
2FeS(CH
3)
2]
+ BF4− and some unreacted cyclopropanation reagent. The latter can be recovered if desired by recrystallization of this mixture from
acetone.
28.
Ferric chloride destroys
ferrocene, a contaminating side product that is difficult to remove by physical means because of its hydrocarbon-like characteristics.
29. The purity of this product is greater than 98% as determined by GLPC (2-m 5% OV-1 or SE-30). The spectral properties are as follows:
1H NMR (300 MHz, CDCl
3, cf. lit.
3) δ: 1.30 (s, 4 H, 2 cyclopropyl CH
2), 7.12–7.40 (m, 10 H, ArH);
13C NMR (75 MHz, CDCl
3) δ: 16.33 (cyclopropyl CH
2), 29.97 (quaternary cyclopropyl C), 125.9 (para C), 128.2, 128.4 (ortho and meta C), 145.8 (ipso C); MS (EI, 70 eV) m/e (rel intensity) 194 (M+, 86), 193 (100), 178 (64), 115 (9).
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
An important advantage of the presently described procedure is that the cyclopropanation reagent is unusually stable for an organometallic compound. Not only is the solid reagent stable to air indefinitely, but its crystallization is accomplished from hot aqueous solutions. Samples of this reagent have been stored in ordinary laboratory reagent bottles for more than five years with no noticeable decomposition. This stability is in contrast to typical Simmons-Smith intermediates and diazoalkanes. Another advantage of the present reagent is that once it has been prepared, its subsequent use in cyclopropanation reactions is trivially straightforward. The reagent can be handled as an ordinary laboratory reagent and combined with an alkene substrate and a suitable solvent in an ordinary flask. Although an inert atmosphere is specified for the present cyclopropanation, these reactions have also been performed routinely in the air with only small reductions in yields.
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
BF4
sodium benzophenone ketyl
Ferrocene
Iron (1+), dicarbonyl(η5-2,4-cyclopentadien-1-yl)(dimethylsulfonium η-methylide)-, tetrafluoroborate (1-)
cyclopentadienyliron dicarbonyl dimer
sodium cyclopentadienyldicarbonylferrate
1,1-diphenyl-2,2-dihalocyclopropanes
acyldiazene
ammonia (7664-41-7)
methanol (67-56-1)
diethyl ether (60-29-7)
hydrogen (1333-74-0)
iron (7439-89-6)
sulfonium ylide (7783-06-4)
nitrogen (7727-37-9)
calcium sulfate (7778-18-9)
acetone (67-64-1)
sodium,
metallic sodium (13966-32-0)
Diphenylmethane (101-81-5)
ferric chloride (7705-08-0)
iodomethane (74-88-4)
1,1-diphenylethene (530-48-3)
Pentane (109-66-0)
Nitromethane (75-52-5)
diiodomethane (75-11-6)
chloromethyl methyl ether (107-30-2)
cyclopropane (75-19-4)
magnesium sulfate (7487-88-9)
dioxane (5703-46-8)
Diazomethane (334-88-3)
zinc-copper
methylene,
carbene (2465-56-7)
boron trifluoride (7637-07-2)
Tetrahydrofuran (109-99-9)
lithium aluminum hydride (16853-85-3)
hexane (110-54-3)
sodium tetrafluoroborate (13755-29-8)
ethylidene
dicyclopentadiene
tert-butyl alcohol (75-65-0)
iron pentacarbonyl
1,1-Diphenylcyclopropane,
Benzene, 1,1'-cyclopropylidenebis- (3282-18-6)
3,3-diphenylpropenoic acid (606-84-8)
trimethyl(3,3-diphenylpropyl)ammonium iodide
pyrazoline
cyclopropyl (2417-82-5)
1,4-dioxane (123-91-1)
chloromethyl methyl sulfide (2373-51-5)
diethyl lithiomethanephosphonate
3-hydroxypropylstannane
2,2-diphenylcyclobutanone
1,1-diphenyl-2-carboxycyclopropane
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