Org. Synth. 1977, 57, 113
DOI: 10.15227/orgsyn.057.0113
3,5,5-TRIMETHYL-2-(2-OXOPROPYL)-2-CYCLOHEXEN-1-ONE
[2-Cyclohexen-1-one, 3,5,5-trimethyl-2-(2-oxopropyl)-]
Submitted by Z. Valenta
1 and H. J. Liu
2.
Checked by T. H. O'Neill, W. Thompson, D. H. Hawke, and R. E. Ireland.
1. Procedure
Caution! Benzene has been identified as a carcinogen; OSHA has issued emergency standards on its use. All procedures involving benzene should be carried out in a well-ventilated hood, and glove protection is required.
A.
7-Acetoxy-4,4,6,7-tetramethylbicyclo[4.2.0]octan-2-one. The apparatus used for the photocycloaddition reaction is shown in
Figure 1. In the reaction vessel is placed a solution of
34.5 g. (0.250 mole) of 3,5,5-trimethyl-2-cyclohexen-1-one (isophorone) (Note 1) and
500 g. (5.00 moles) (Note 2) of 1-propen-2-yl acetate (Note 3) in
625 ml. of benzene. A constant and moderate flow of
argon (Note 4) is maintained, agitating the solution throughout the reaction period. The trap is filled with
2-propanol and dry ice
(Note 5). The solution is irradiated with a
450-watt, Hanovia high-pressure, quartz, mercury vapor lamp, using a
Pyrex filter, for 96 hours
(Note 6). Concentration of the resulting solution under reduced pressure (
water aspirator) gives
65–80 g. of crude
7-acetoxy-4,4,6,7-tetramethylbicyclo[4.2.0]octan-2-one (Note 7).
Figure 1. A, Dewar flask; B, sintered-glass filter; C, metal cooling coil; D, water inlet; E, water outlet; F, reaction vessel; G, quartz immersion well; H, Pyrex filter; I, lamp; J, nitrogen gas inlet; K, ground glass joint; L, condenser; M, calcium chloride drying tube.
B. 7-Hydroxy-4,4,6,7-tetramethylbicyclo[4.2.0]octan-2-one. The preceding crude photo-adduct is dissolved in 250 ml. of methanol and transferred to a 1-l., three-necked, round-bottomed flask fitted with overhead stirrer with Teflon blade, addition funnel, and argon inlet. The solution is cooled with an ice bath, and 500 ml. of 4 M aqueous sodium hydroxide is added, with stirring, over a period of 20 minutes. Upon completion of the addition, the ice bath is removed, and stirring is continued for 16 hours. The brown solution is extracted with four 500-ml. portions of chloroform. The organic extract is washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Distillation of the residue through a 6-cm. Vigreux column affords, after a small forerun, 23.0–27.9 g. (47–57%) of 7-hydroxy-4,4,6,7-tetramethylbicyclo[4.2.0]octan-2-one (Note 8), collected at 92–101° (0.2 mm.).
C. 3,5,5-Trimethyl-2-(2-oxopropyl)-2-cyclohexen-1-one. A 2-l., three-necked, round-bottomed flask, fitted with an overhead stirrer with Teflon blade, a Fries condenser, and a stopper, is charged with a solution of 9.8 g. (0.050 mole) of 7-hydroxy-4,4,6,7-tetramethylbicyclo[4.2.0]octan-2-one in 600 ml. of 50% (by volume) aqueous acetonitrile, and 82 g. (0.15 mole) (Note 9) of ceric ammonium nitrate (Note 10) is added in one portion with stirring. Immediately after completion of the addition, the flask is immersed in an oil bath preheated to 170°. Refluxing occurs in about 10 minutes and is continued for 5 minutes. During this period the color of the solution changes from light brown to pale yellow. At the end of this time the reaction mixture is immediately poured onto crushed ice and extracted with four 600-ml. portions of chloroform. The combined extracts are washed with saturated sodium hydrogen carbonate and saturated sodium chloride, dried over magnesium sulfate, and filtered. The solvent is removed under reduced pressure, and the residue distilled, using a short-path distillation apparatus. All material boiling at 70–100° (0.25 mm.) is collected. Fractionation of the yellow oil through a 6-cm. Vigreux column gives 4.68–4.71 g. (48–50%) of 3,5,5-trimethyl-2-(2-oxopropyl)-2-cyclohexene-1-one, b.p. 81–85° (0.4 mm.) (Note 11).
2. Notes
1.
Isophorone obtained from M C and B Manufacturing Chemists was freshly distilled, b.p.
73° (4.5 mm.).
2.
To minimize the formation of
cyclohexenone dimer and achieve a cleaner photo-adduct, it is essential to use a large excess of olefin.
33.
1-Propen-2-yl acetate was supplied by Aldrich Chemical Company, Inc.4.
Submitters used
nitrogen purified by passing it through a set of gas
wash bottles containing Fieser's solution,
4 concentrated
sulfuric acid, sodium hydroxide, and
calcium chloride.
5.
The submitters filled the
Dewar flask with ice and water. After 2 hours the ice had melted and water was left in the flask for cooling.
6.
The progress of the reaction was monitored by injecting, after each 24-hour period, an aliquot into a GC and checking the peak corresponding to
isophorone. Alternatively, TLC (E. Merck 0.25-mm. silica gel plates developed with
ethyl acetate) can be used.
7.
This crude product is contaminated mainly by polymeric compounds. An attempted distillation of this material was unsuccessful; partial decomposition occurred at 110–125° (0.3 mm.). If it is desirable, purification can be achieved by extensive silica gel column chromatography with
5% ether in benzene.
8.
The product is a mixture of at least two diasteriomers as indicated by its
1H NMR spectrum (CCl
4), showing eight singlets at δ 0.9–1.22, for a total of twelve methyl protons. Its IR spectrum (neat) exhibits absorption bands at 3440 and 1695 cm.
−1 A molecular ion peak at 196.1447 (calcd. for C
12H
20O
2:196.1463) is displayed in its mass spectrum.
9.
Use of less of the reagent resulted in partial recovery of the starting material.
10.
Ceric ammonium nitrate was supplied by Fisher Scientific Company.
11.
IR (neat) cm.
−1: 1720, 1670, 1645;
1H NMR (CDCl
3), δ: 1.03, 1.87, 2.13, 2.20, 2.25, 3.43 (all singlets); mass spectrum
m/e 194.1299 (M
+).
3. Discussion
Recently, the application of photocycloaddition reactions to organic synthesis has been gaining importance.
5,6 The procedure described is illustrative of a general method,
3 based on a photocycloaddition reaction, for the introduction of an activated alkyl group specifically to the α-carbon atom of an α,β-unsaturated cyclohexenone. Especially significant is the fact that the method is also applicable to α,β-unsaturated cyclohexenones which do not possess enolizable γ-hydrogen atoms and to which normal alkylation reactions
7 cannot be applied. A closely related procedure involving the photocycloaddition of
vinyl acetate to 2-cyclohexenones (in which enolization toward the 6-position is forbidden) followed by bromination and fragmentation of the adduct has been reported.
3,8 It has also been observed
9 that photoadducts of cycloalkenones and
vinylene carbonate undergo fragmentation upon alkali treatment, giving 2-(2-oxoethyl)-2-cycloalken-1-ones.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
cyclohexenone dimer
calcium chloride (10043-52-4)
Benzene (71-43-2)
ethyl acetate (141-78-6)
methanol (67-56-1)
ether (60-29-7)
acetonitrile (75-05-8)
sodium hydroxide (1310-73-2)
chloroform (67-66-3)
sodium hydrogen carbonate (144-55-8)
sodium chloride (7647-14-5)
nitrogen (7727-37-9)
2-propanol (67-63-0)
magnesium sulfate (7487-88-9)
1-propen-2-yl acetate (108-22-5)
vinyl acetate (108-05-4)
argon (7440-37-1)
isophorone,
3,5,5-trimethyl-2-cyclohexen-1-one
ceric ammonium nitrate
3,5,5-Trimethyl-2-(2-oxopropyl)-2-cyclohexen-1-one,
2-Cyclohexen-1-one, 3,5,5-trimethyl-2-(2-oxopropyl)-,
3,5,5-trimethyl-2-(2-oxopropyl)-2-cyclohexene-1-one (61879-73-0)
7-Acetoxy-4,4,6,7-tetramethylbicyclo[4.2.0]octan-2-one (66016-89-5)
7-Hydroxy-4,4,6,7-tetramethylbicyclo[4.2.0]octan-2-one (61879-76-3)
sulfuric acid, sodium hydroxide
vinylene carbonate
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