Organic Syntheses, CV 6, 142
Submitted by C. W. Jefford
1 2, J. Gunsher
1, D. T. Hill
1, P. Brun
3, J. Le Gras
3, and B. Waegell
3.
Checked by R. W. Begland and R. E. Benson.
1. Procedure
A.
exo-3,4-Dichlorobicyclo[3.2.1]oct-2-ene. A
1-l., four-necked, round bottomed flask is fitted with an
efficient stirrer, a
thermometer, a
reflux condenser protected by a
calcium chloride tube, and a
500-ml., stoppered, pressure-equalizing addition funnel. After the addition of a solution of
52.5 g. (0.558 mole) of norbornene (Note
1) in
400 ml. of petroleum ether ((Note
2), b.p.
45–60°) to the flask,
112 g. (2.06 moles) of sodium methoxide (Note
3) is added, and stirring is begun. The flask is immersed in an ice–salt mixture (Note
4) before
349 g. (1.82 moles) of ethyl trichloroacetate (Note
5) is placed in the addition funnel and allowed to drip slowly into the stirred mixture at a rate such that the temperature does not rise above 0° (Note
6). The addition requires about 4 hours, and the originally white reaction mixture becomes increasingly yellow in color. The mixture is stirred at a temperature below 0° for 4 hours (Note
6) before the temperature is allowed to rise gradually to room temperature overnight. The reaction mixture is poured onto 500 g. of crushed ice in 300 ml. of water. After the ice has melted, the organic layer is separated, and the aqueous layer is shaken with four
200-ml. portions of diethyl ether. The aqueous layer is neutralized with
10% hydrochloric acid and shaken again with two
200-ml. portions of ether. The original organic layer and the
ether extractions are combined, washed with
300 ml. of a saturated solution of sodium chloride, dried for 6 hours over
20 g. of anhydrous magnesium sulfate, filtered, and concentrated to about 200 ml. by distillation. The resulting product is distilled through a
20-cm. Vigreux column, giving
72.5–87.0 g. (
74–88%) of
exo-3,4-dichlorobicyclo[3.2.1]oct-2-ene as a colorless liquid, b.p.
72–73° (0.9 mm.),
nD25 1.5333 (Note
7) and (Note
8).
B.
3-Chlorobicyclo[3.2.1]oct-2-ene. A
2-l., three-necked, round-bottomed flask equipped with a stirrer, a reflux condenser protected by a calcium chloride tube, and a 500-ml., stoppered, pressure-equalizing addition funnel is charged with
350 ml. of dry ether and
15 g. (0.40 mole) of powdered lithium aluminum hydride (Note
9). The flask is placed in a mixture of ice and water, and
1050 ml. of dry tetrahydrofuran (Note
10) is added. Stirring is begun, and a solution of
39.5 g. (0.224 mole) of exo-3,4-dichlorobicyclo[3.2.1]oct-2-ene in
50 ml. of dry tetrahydrofuran (Note
10) is added dropwise from the addition funnel over a 30-minute period. After the addition is complete, the reaction mixture is heated under gentle reflux for 18 hours. The mixture is cooled to 0°, and the remaining
lithium aluminum hydride is decomposed by the careful addition of wet
ether, followed by the cautious dropwise addition of 10 ml. of water. The resulting mixture is poured onto 500 g. of crushed ice in 200 ml. of water. After the ice has melted, the organic layer is separated, and the aqueous layer is acidified to a pH of 5–6 with
10% hydrochloric acid, dissolving the lithium and aluminum salts present (Note
11). The aqueous solution is shaken five times with
200-ml. portions of ether. The organic layers are combined, washed with
200 ml. of a saturated solution of sodium chloride, and dried overnight over
20 g. of anhydrous magnesium sulfate. The
ether and
tetrahydrofuran are removed by distillation at atmospheric pressure, and the product is distilled through a 20-cm. Vigreux column, yielding
23.5–23.9 g. (
74–75%) of
3-chlorobicyclo[3.2.1]oct-2-ene as a colorless oil, b.p.
76–77° (21 mm.),
nD20 1.5072 (Note
12).
C.
Bicyclo[3.2.1]octan-3-one. A
magnetic stirring bar is placed in a
300-ml., round-bottomed flask and
100 ml. of concentrated sulfuric acid (Note
13) is added Stirring is begun, the flask is cooled in an
ice bath, and
9.0 g. (0.63 mole) of 3-chlorobicyclo[3.2.1]oct-2-ene is added in one portion. The mixture is stirred, allowed to warm slowly over 4 hours to room temperature, then stirred overnight. The resulting solution is poured onto 200 g. of ice with stirring. After the ice has melted, the mixture is shaken with three
100-ml. portions of ether. The
ether layers are combined, washed once with 50 ml. of water, and dried over
10 g. of magnesium sulfate. The
ether is removed by careful distillation, and the crude product is sublimed at a bath temperature of 70° (15 mm.) directly onto a cold finger inserted into the flask. The crude product is twice sublimed, yielding
5.9–6.3 g. (
75–81%) of
bicyclo[3.2.1]octan-3-one, m.p.
137°, 98% pure by analysis (Note
14), (Note
15), and (Note
16).
2. Notes
2. The
petroleum ether used must be olefin-free.
3. The submitters used
sodium methoxide available from Schuchardt, Ainmillerstrasse 25, 8-Munich 13, Germany. The checkers used product available from Matheson, Coleman and Bell.
4. An amount sufficient to fill a
5-l. container is recommended.
5. It is used as purchased from either Schuchardt or Eastman Organic Chemicals. It appears that when equimolar amounts of
carbene precursor and olefin are used, the adduct is obtained in only 25% yield.
4
6. Efficient stirring and maintenance of a low temperature are required if high yields are to be obtained.
7. For the final distillation the pressure is regulated with a manostat.
8. The IR spectrum (neat) shows absorption at 1645, 1450, 1305, 1223, 1052, 974, 959, 866, 796, and 750 cm.
−1. The
1H NMR spectrum (CCl
4) shows absorption at δ 4.1 (d,
J 
3 Hz.), and 6.08 (d,
J 
4 Hz) attributable to the vinyl and allyl protons, respectively
9. This was purchased from Metal Hydrides, Inc., and is also obtainable from Schuchardt.
11. A small amount of insoluble material may remain at this point. If it interferes with the extraction procedure it may be removed by filtration.
12. The IR spectrum (neat) shows absorption at 1635, 1440, 1038, 952, 841, 833, and 685 cm.
−1. The
1H NMR spectrum (CCl
4) shows three major peaks between δ 2.0–2.8 and a doublet at 5.91 (
J 
Hz., 1H, C
H)
14. The IR spectrum (Nujol) has an intense band at 1710 cm.
−1. The
1H NMR spectrum (CDCl
3) has a broad peak at δ 1.7 (6H), a sharp peak at 2.35 (4H) and a broad peak at 2.55 (2H).
15. The GC data were obtained using
3 m. × 7 mm. column packed with nonacid-washed Chromosorb 45/60 W containing 15% 200M Apiezon silicone oil as the immobile phase.
16. The oxime has m.p.
96°. The ketone can be further purified
via the semicarbazone derivative, which can be purified by crystallization and subsequently hydrolyzed by dilute
hydrochloric acid.
3. Discussion
The present procedure is a refinement of existing methods,
6,7,8,9 an adaption of the method of Parham and Schweizer
10 that furnishes the carbene adduct in higher yield than other methods. The submitters' studies indicate that the procedure of Doering,
11 involving the interaction of
chloroform with
potassium tert-butoxide, is unsatisfactory since traces of
tert-butyl alcohol present react with the rearranged adduct during the reduction step. In addition, the yields of adduct are poor (4–15%).
4 The method of Wagner,
12 utilizing the pyrolysis of
sodium trichloroacetate, is easy to perform, but the yields of initial adduct are poor (13%). That of Seyferth,
13 involving the pyrolysis of
phenyltrichloromethylmercury, gives the adduct in 45% yield. However, the higher cost and additional steps entailed in the preparation of the reagent, together with the hazards associated with
mercury, detract from its use.
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