Organic Syntheses, CV 7, 473
Submitted by Vinayak V. Kane and Maitland Jones Jr
1.
Checked by R. V. Stevens and R. P. Polniaszek.
1. Procedure
Caution! The following reactions should be performed in an efficient hood to protect the experimentalist from noxious vapors (piperidine and methyl vinyl ketone).
A.
1-(Cyclooctylidenemethyl)piperidine. Cyclooctanecarboxaldehyde (12.5 g, 0.089 mol) (Note
1) and
piperidine (8.35 g, 0.098 mol) are dissolved in
115 mL of toluene and placed in a
250-mL, one-necked flask equipped with a magnetic stirring bar and Dean-Stark water separator, on top of which is a condenser fitted with a nitrogen-inlet tube. The reaction mixture is placed under a nitrogen atmosphere, then brought to and maintained at reflux with stirring for 6 hr, at which time the theoretical amount of water (1.75 mL) has been collected. The reaction mixture is cooled and fractionally distilled under reduced pressure (Note
2);
toluene and excess
piperidine are removed at 40°C (0.5 mm), and the enamine product is distilled as a colorless liquid to yield
17.30 g (
0.084 mol,
93.6%) of
1-(cyclooctylidenemethyl)piperidine, bp
81–83°C (0.5 mm).
B.
Spiro[5.7]tridec-1-en-3-one. A dry,
1-L, three-necked flask is equipped with a Teflon stirring bar, condenser, pressure-equalizing dropping funnel, and nitrogen-inlet tube. To this flask are introduced
absolute ethanol (460 mL) (Note
3) and
1-(cyclooctylidenemethyl)piperidine (17.3 g. 0.084 mol). After the solution has been stirred for 5 min,
methyl vinyl ketone (6.44 g, 0.092 mol) (Note
4) is added dropwise over a period of 5 min. The solution is refluxed for 20 hr using a heating mantle. The mixture is cooled and
anhydrous sodium acetate (15.0 g), acetic acid (25.5 mL), and water (46 mL) are added. The mixture is brought to and maintained at reflux for 8 hr. The heat is removed and the solution is cooled with ice water;
aqueous sodium hydroxide (20% solution, approximately 65 mL) is added until pH 9–10 is attained. The solution is refluxed for another 15 hr; at the end of this period the reaction mixture is cooled. The reaction mixture (600 mL) is divided equally into two
2-L separatory funnels and each portion is diluted with 600 mL of ice-cold water. Each separatory funnel is extracted with
ether (3 × 125 mL). The
ether extract is washed successively with aqueous
5% hydrochloric acid (125 mL) and
saturated brine (3 × 170 mL), dried over anhydrous
magnesium sulfate, and filtered. The solvent is removed on a
rotary evaporator and the product is distilled under vacuum (Note
5) as a colorless liquid to yield
7.05–7.75 g (
44–49%) of
spiro[5.7]tridec-1-en-3-one, bp
95–125°C (0.5 mm) (Note
6).
C.
Spiro[5.7]trideca-1,4-dien-3-one. Spiro[5.7]tridec-1-en-3-one (3.63 g, 0.0189 mol) and
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (8.90 g, 0.0392 mol) (Note
7) are dissolved in
50 mL of dioxane (Note
8) in a
250-mL, one-necked flask equipped with a magnetic stirring bar and fitted with a condenser and drying tube. The reaction mixture is brought to and maintained at reflux with stirring for 6 hr. The mixture is cooled, filtered, and the
dioxane removed in a rotary evaporator. The product is taken up in
ether (125 mL), and the
ether layer is washed with aqueous
sodium hydroxide (15%, 4 × 60 mL). The combined aqueous layers are further extracted with
ether (3 × 60 mL). The
ether layers are combined and washed with saturated
sodium chloride (4 × 60 mL), dried over anhydrous
magnesium sulfate and filtered. The solvent is removed on the rotary evaporator to afford a crude yellow liquid. To this crude product are added
silica gel (6.25 g) (Note
9) and enough
ether to cover the
silica gel. The
ether is removed with a rotary evaporator so as to absorb the crude product on the
silica gel. This
silica gel dry powder is poured onto a
column (12 in. long × 1.0 in. diameter) containing silica gel (50 g) in
hexane. The column is eluted with
hexane (70 mL) and then with an increasing amount of
ethyl acetate/
hexane (Note
10). The desired fractions are combined (Note
11) and solvent is removed under vacuum to afford
spiro[5.7]trideca-1,4-dien-3-one (
2.65 g,
73.7%), (Note
12).
2. Notes
3. Absolute
ethanol, distilled and stored over molecular sieves, was used.
4.
Methyl vinyl ketone (bp 35–36°C at 140 mm) was obtained from Aldrich Chemical Company, Inc. and distilled immediately before use.
5. A heating mantle was used for this distillation. A forerun of 25–95°C (0.5 mm) was discarded. The exact boiling point of
spiro[5.7]tridec-1-en-3-one is
86°C (0.1 mm).
6. The product has the following spectral properties:
1H NMR (CCl
4) δ: 1.62 (s, 14 H), 1.85 (br d, 2 H), 2.25 (m, 2 H), 5.68 (d, 1 H,
J = 10 Hz), 6.75 (d, 1 H,
J = 10 Hz).
9.
silica gel analytical reagent (60–200 mesh) was obtained from the J. T. Baker Chemical Co.
10. The
silica gel column was eluted starting with
hexane (70 mL), followed by 2% ethyl acetate–hexane (100 mL); 5% ethyl acetate–hexane (100 mL); 10% ethyl acetate–hexane (600 mL). The fractions were monitored with 20% ethyl acetate–hexane, using silica 7 GF plates (purchased from Analtech, Inc.), thickness 250 μm, 20 cm long × 5 cm wide. The plates were sprayed with
3% ceric sulfate and heated at 350°C to detect dienone and monoenone. Alternatively,
silica gel 60 F-254 plates (purchased from EM Laboratories, Inc.), thickness 25 mm, 20 cm long × 5 cm wide may be used. Detection may be made with ultraviolet light. The ratio of 1 g of crude dienone to
15 g of silica gel is adequate for obtaining pure
spiro[5.7]trideca-1,4-dien-3-one.
11. When
20% ethyl acetate/hexane is used, the monoenone,
Rf 0.57, and the dienone,
Rf 0.47 (Analtech Uniplate–Silica 7 GF), are obtained.
12. The product has the following spectral properties:
1H NMR (CCl
4) δ: 1.65 (s, 14 H), 6.10 (d, 2 H),
J = 10 Hz), 6.98 (d, 2 H,
J = 10 Hz).
3. Discussion
This procedure illustrates a general method for preparing a wide range of spirocyclohexenones and hence spirocyclohexadienones. A number of intramolecular and intermolecular reactions are known to give spirodienones; however, these methods have limited synthetic application.
2 This procedure is superior
3 to that developed by Bordwell and Wellman
4 for side reactions such as aldol condensation of the aldehyde and polymerization of
methyl vinyl ketone are avoided. These spirodienones are useful intermediates in the synthesis of paracyclophanes.
5,6
Cyclopentanecarboxaldehyde (47%),
cyclohexanecarboxaldehyde (41%),
1,2,5,6-tetrahydrobenzaldehyde (43%),
cycloheptanecarboxaldehyde (41%),
cyclooctanecarboxaldehyde (42%),
cycloundecanecarboxaldehyde (36%),
5-norbornene-2-carboxaldehyde (32%),
adamantanecarboxaldehyde (20%), and
1,2,3,4-tetrahydro-1-naphthylaldehyde (40%) gave corresponding spiroenones.
7 Spiroenones obtained from
cyclohexanecarboxaldehyde,
cycloheptanecarboxaldehyde and
cyclooctanecarboxaldehyde were converted to the corresponding dienones using the
dichlorodicyanobenzoquinone (DDQ). The yields for all three dienones are in the range of 56 to 58%.
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
silica gel
brine
ethanol (64-17-5)
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
ethyl acetate (141-78-6)
ether (60-29-7)
sodium acetate (127-09-3)
sodium hydroxide (1310-73-2)
sodium chloride (7647-14-5)
nitrogen (7727-37-9)
potassium hydroxide (1310-58-3)
toluene (108-88-3)
piperidine (110-89-4)
magnesium sulfate (7487-88-9)
dioxane (5703-46-8)
hexane (110-54-3)
methyl vinyl ketone (78-94-4)
Cyclohexanecarboxaldehyde (2043-61-0)
Cyclopentanecarboxaldehyde (872-53-7)
ceric sulfate (13590-82-4)
2,3-dichloro-5,6-dicyano-1,4-benzoquinone,
dichlorodicyanobenzoquinone
1,2,5,6-tetrahydrobenzaldehyde
Spiro[5.7]trideca-1,4-dien-3-one (41138-71-0)
Cyclooctanecarboxaldehyde (6688-11-5)
1-(Cyclooctylidenemethyl)piperidine (65226-88-2)
Spiro[5.7]tridec-1-en-3-one (60033-39-8)
cycloheptanecarboxaldehyde
cycloundecanecarboxaldehyde
5-norbornene-2-carboxaldehyde
adamantanecarboxaldehyde
1,2,3,4-tetrahydro-1-naphthylaldehyde
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved