Org. Synth. 1989, 67, 205
DOI: 10.15227/orgsyn.067.0205
3-HYDROXY-1-CYCLOHEXENE-1-CARBOXALDEHYDE
[1-Cyclohexene-1-carboxaldehyde, 3-hydroxy-]
Submitted by H. L. Rigby, M. Neveu, D. Pauley, B. C. Ranu, and T. Hudlicky
1.
Checked by Denis R. St. Laurent and Leo A. Paquette.
1. Procedure
A. 1-(1,3-Dithian-2-yl)-2-cyclohexen-1-ol (2). To a suspension of 1,3-dithiane (Note 1) (12 g, 0.1 mol) in dry tetrahydrofuran (100 mL) (Note 2) at −78°C is added butyllithium (40 mL, 2.5 M, 0.1 mol). The reaction is stirred for 2 hr. Initially the dithiane dissolves, followed by precipitation of the lithio salt. After 2 hr, 2-cyclohexen-1-one (9.6 g, 0.1 mol) (Note 3) in dry tetrahydrofuran (20 mL) is added dropwise. After about half of the cyclohexenone is added, the mixture becomes homogeneous. After the addition is complete, the reaction is stirred for an additional 30 min at −78°C and then stored for 18 hr at 0°C. The solution is concentrated to one-fourth volume under reduced pressure. Water (100 mL) is added and the mixture is extracted with ether (3 × 50 mL). The extract is dried over sodium sulfate and evaporated to give an oil that is vacuum-distilled to give 14.0–14.7 g (65–68%) of the protected aldehyde 2, bp 149–153°C (0.8–1.0 mm) (Note 4).
B.
3-Hydroxy-1-cyclohexene-1-carboxaldehyde (3). The
hydroxy thioacetal 2 (5.5 g, 0.025 mol) in
25 mL of tetrahydrofuran is added dropwise to a mechanically stirred suspension of
red mercuric oxide (11 g, 0.051 mol) (Note 5) and
boron trifluoride etherate (7.2 g, 0.051 mol) (Note 6) in refluxing
15% aqueous tetrahydrofuran (50 mL). After the addition is complete, the mixture is stirred
(Note 7) at reflux for an additional 2 hr. Another
5.5 g of red mercuric oxide is added and the reaction is stirred at reflux for 1 hr. The reaction is cooled to room temperature and
ether (150 mL) is added, followed by
50 mL of brine. The mixture is filtered and the residue washed with
ether (3 × 50 mL). The organic layer is separated and washed with saturated
sodium bicarbonate solution (2 × 50 mL) and
brine (1 × 50 mL). The organic layer is dried over
sodium sulfate and the solvent evaporated to leave a residual oil. This oil is purified by medium-pressure liquid chromatography (silica gel, elution with
40% ethyl acetate in hexane) to give
1.5–1.6 g (
47–50%) of the aldehyde
3, bp
125°C (0.075 mm) (Kugelrohr)
(Note 8).
2. Notes
1.
Dithiane was obtained from Aldrich Chemical Company, Inc. and was used without purification.
2.
Tetrahydrofuran was distilled under
nitrogen from
potassium and
benzophenone.
3.
2-Cyclohexen-1-one was obtained from Aldrich Chemical Company, Inc. and used as received.
4.
The submitters report bp
157°C (1 mm). The spectral properties of 2 are as follows: IR (neat) cm
−1: 3450 (br), 3030, 2940, 2900 (sh), 2830, 1645 (w), 1425, 1280, 1185, 1085, 985;
1H NMR (CDCl
3, 300 MHz) δ: 1.57–2.08 (m, 8 H), 2.40 (s, 1 H), 2.74–2.90 (m, 4 H), 4.17 (s, 1 H), 5.68 (d, 1 H,
J = 10.05), 5.85–5.91 (m, 1 H);
13C NMR (CDCl
3, 20 MHz) δ: 18.53, 24.98, 25.75, 30.35, 30.54, 33.03, 59.54, 71.75, 129.43, 132.18; MS: M
+ 198, 120, 119 (base), 97, 91 (no M
+ peak).
5.
Mercuric oxide (red) was purchased from Aldrich Chemical Company, Inc. and used without purification.
6.
Boron trifluoride etherate was distilled from
calcium hydride at aspirator pressure.
7.
Mechanical stirring was found to be essential, and in some cases addition of sea sand to the reaction mixture reduced clogging of the reagents and led to higher yields.
8.
The submitters report bp
70°C (10−4 mm). The spectral properties of
3 are as follows: IR (neat) cm
−1: 3400 (br), 2950, 2870, 2720, 1675, 1435, 1305, 1180, 1135, 1070, 1045, 995, 965, 925;
1H NMR (CDCl
3, 300 MHz) δ: 1.47–1.54 (m, 2 H), 1.71–1.79 (m, 1 H), 1.90–1.98 (m, 1 H), 2.06 (s, 2 H), 3.49 (br s, 1 H), 4.37 (br s, 1 H), 6.63 (s, 1 H), 9.34 (s, 1 H);
13C NMR (CDCl
3, 75 MHz) δ: 18.54, 20.94, 31.35, 65.84, 77.43, 141.63, 150.88, 194.49; MS: M
+ 97 (base), 79, 69, 55, 41.
3. Discussion
Preparation of a compound such as
3 is useful where extensive functionalization of a cyclic enone is required. In addition to
3,
4,4-dimethyl-3-hydroxy-1-cyclopentene-1-carboxaldehyde was prepared using the same procedure from
4,4-dimethyl-2-cyclopenten-1-one.
2 Table I gives yields and physical properties for this compound, which has been used as a starting material in the syntheses of
coriolin and
pentalenic acid.
3,4
TABLE I
PREPARATION OF 4,4-DIMETHYL-3-HYDROXY-1-CYCLOPENTENE-1-CARBOXALDEHYDE
|
|
Enone
|
Dithiane
|
Hydroxy Aldehyde
|
|
|
|
|
|
|
|
79%
|
55%
|
|
|
bp 130–132°C, 0.05 mm
|
|
|
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
brine
red mercuric oxide
Mercuric oxide (red)
coriolin
Hydroxy Aldehyde
ethyl acetate (141-78-6)
ether (60-29-7)
sodium bicarbonate (144-55-8)
sodium sulfate (7757-82-6)
nitrogen (7727-37-9)
Benzophenone (119-61-9)
potassium (7440-09-7)
butyllithium (109-72-8)
Tetrahydrofuran (109-99-9)
hexane (110-54-3)
boron trifluoride etherate (109-63-7)
dithiane (505-20-4)
calcium hydride (7789-78-8)
2-cyclohexen-1-one,
cyclohexenone (930-68-7)
1,3-Dithiane (505-23-7)
4,4-Dimethyl-2-cyclopenten-1-one (22748-16-9)
3-Hydroxy-1-cyclohexene-1-carboxaldehyde,
1-Cyclohexene-1-carboxaldehyde, 3-hydroxy- (67252-14-6)
1-(1,3-Dithian-2-yl)-2-cyclohexen-1-ol (53178-46-4)
4,4-dimethyl-3-hydroxy-1-cyclopentene-1-carboxaldehyde
pentalenic acid
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved