Process for preparing spirogalbanone

Abstract

A method of making spirogalbanone includes the steps of: (a) subjecting ethynylspirodecanol to a Rupe rearrangement to give a compound of the formula I ##STR00001## (b) converting the compound of (a) to a C1-C4 alkyl acetal; (c) subjecting the acetal to a trans-acetalization reaction with allyl alcohol in the presence of a mild acid catalyst; (d) heating the product of (c) in the presence of an acid catalyst to give an allylenolether; and (e) subjecting the product of (d) to a Claisen rearrangement to give spirogalbanone. The method affords an easier and more efficient method of preparation.

Claims

1. A method of making spirogalbanone comprising the steps of: (a) subjecting ethynylspirodecanol to a Rupe rearrangement to give a compound of the formula I ##STR00012## (b) converting the compound of (a) to a C1-C4 alkyl acetal; (c) subjecting the acetal to a trans-acetalisation reaction with allyl alcohol in the presence of a mild acid catalyst; (d) heating the product of (c) in the presence of an acid catalyst to give an allylenolether; and (e) subjecting the product of (d) to a Claisen rearrangement to give spirogalbanone.

2. The method according to claim 1, in which the acetal formation of step (b) is caused by the reaction of the compound of Formula I with an alcohol and a corresponding trialkylorthoformate in the presence of a strong acid catalyst.

3. The method according to claim 1, in which step (b) is carried out at a temperature below 0 C.

4. The method according to claim 1, in which steps (c) and (d) are performed together.

5. A compound of the formula I ##STR00013##

6. The compound according to claim 5 selected from the compounds of Formulae Ia and Ib: ##STR00014##

7. The method according to claim 1, in which step (b) is carried out at a temperature between 10 and 5 C.

8. The method according to claim 2, wherein the strong acid catalyst is selected from at least one of sulphuric acid and methanesulphonic acid.

Description

(1) The disclosure is further described with reference to the following non-limiting examples in which all parts are by weight. (a) Preparation of Compound of Formula I:

(2) A reactor was charged with 714 parts formic acid and 161 parts water. The temperature was raised to 95-100 C. and 500 parts ethynylspirodecanol (86.6% by weight) were added over a period of 30 minutes. The temperature was maintained until reaction was complete (about 9 hours).

(3) The reaction mixture was then cooled to 30-40 C. and 250 parts each of 10% brine and heptane were added. The mixture was stirred for 15 minutes and allowed to settle for 15 minutes, at which point the lower (aqueous) layer was run off. To this aqueous layer, a further 300 parts of heptane was then added, and the 15 minutes stirring/15 minutes settle/aqueous layer drain repeated. The resulting two organic fractions were combined and washed three times each with 250 parts 10% brine. The solvent was removed in a rotary evaporator to give 481 parts of crude material (65-70% pure). The crude material was flash distilled to give 322 parts of the compound of Formula I (70% yield at 90% purity)

(4) ##STR00008##

(5) .sup.1H NMR (400 MHz, CDCl.sub.3) (major isomer): 6.91 (tt, J=3.9, 1.7 Hz, 1H, 11-CH), 2.34-2.28 (m, 2H, 12-CH.sub.2), 2.29 (s, 3H, 2-CH.sub.3), 2.12-2.10 (m, 2H, 9-CH.sub.2), 1.67-1.58 (m, 4H, 5-CH.sub.2, 6-CH.sub.2), 1.49-1.45 (m, 2H, 13-CH.sub.2), 1.39-1.34 (m, 4H, 4-CH.sub.2, 7-CH.sub.2) ppm.

(6) .sup.13C NMR (100 MHz, CDCl.sub.3) (major isomer): 199.1 (s, 1-CO), 140.3 (d, 11-CH), 139.0 (s, 10-C), 40.3 (s, 8-C), 37.9 (2t, 4-CH.sub.2, 7-CH.sub.2), 35.0 (t, 9-CH.sub.2), 32.6 (t, 13-CH.sub.2), 25.0 (q, 2-CH.sub.3), 24.6 (t, 12-CH.sub.2), 24.1 (2t, 5-CH.sub.2, 6-CH.sub.2) ppm.

(7) ##STR00009##

(8) .sup.1H NMR (400 MHz, CDCl.sub.3) (minor isomer): 6.62 (t, 1H, J=1.5 Hz, 9-CH), 2.28 (s, 3H, 2-CH.sub.3), 2.18 (td, J=6.2, 1.7 Hz, 2H, 11-CH.sub.2), 1.75-1.70 (m, 4H, 5-CH.sub.2, 6-CH.sub.2), 1.67-1.52 (m, 6H, 4-CH.sub.2, 7-CH.sub.2, 12-CH.sub.2), 1.48-1.45 (m, 2H, 13-CH.sub.2) ppm.

(9) .sup.13C NMR (100 MHz, CDCl.sub.3) (minor isomer): 199.3 (s, 1-CO), 149.4 (d, 9-CH), 137.0 (s, 10-C), 44.1 (s, 8-C), 39.8 (2t, 4-CH.sub.2, 7-CH.sub.2), 34.0 (t, 13-CH.sub.2), 24.9 (q, 2-CH.sub.3), 24.4 (2t, 5-CH.sub.2, 6-CH.sub.2), 23.0 (t, 11-CH.sub.2), 20.0 (t, 12-CH.sub.2) ppm. (b) Preparation of Spirogalbanone

(10) 362.1 parts of the compound of Formula I prepared as previously described was added to a reactor with 94.6 parts methanol, and the mixture cooled to 8 C. under nitrogen. 2.8 parts 98% sulphuric acid was then added and the temperature maintained within the range 5 to 10 C. To this mixture 252.8 parts of trimethyl orthoformate was added over a period of 2 hours, and the mixture stirred at this temperature for 3.5 hours.

(11) The temperature was then raised to 0 C. over a period of 20 minutes and 8.4 parts sodium acetate added. Stirring at 0 C. was continued for 30 minutes, during which time the colour of the reaction mixture changed from black-grey to clear orange. The pH was checked to ensure that it is 3 minimum, with more sodium acetate being added to maintain this pH, if necessary

(12) The temperature of the reaction mixture was raised to 20-25 C. and 249.7 parts allyl alcohol and 2.9 parts citric acid added. The temperature was then slowly raised to 150 C. over a period of 7 hours with distillation. The mixture was sampled regularly and checked by GC analysis. When the amount of product remained the same (within 1% difference), the reaction was stopped by cooling to 40 C. and adding 200 parts heptane and 340 parts water. The mixture was stirred for 15 minutes, allowed to settle for a further 15 minutes and the lower (aqueous) layer drained. This process was repeated with the aqueous layer with 100 parts heptane. The two heptane layers were then combined and washed with 340 parts of 10% brine, followed by 300 parts 10% sodium carbonate solution.

(13) Solvent was distilled off in a rotary evaporator, to give 484.3 parts oil.

(14) 50 parts of paraffin oil was added to the oil and the mixture subjected to flash distillation by means of a 3 cm Vigreux column at 1 mbar pressure to give 351.8 parts spirogalbanone in the fractions. Yield was 90.4%

(15) ##STR00010##

(16) .sup.1H NMR (400 MHz, CDCl.sub.3) (major isomer): 6.90 (tt, J=3.9, 1.7 Hz, 1H, 14-CH), 5.89-5.78 (m, 1H, 4-CH), 5.07-5.00 (m, 1H, 5=CH.sub.a), 4.98-4.94 (m, 1H, 5=CH.sub.b), 2.74 (t, J=7.8 Hz, 2H, 2-CH.sub.2), 2.38-2.28 (m, 4H, 3-CH.sub.2, 15-CH.sub.2), 2.12-2.11 (m, 2H, 12-CH.sub.2), 1.68-1.53 (m, 4H, 8-CH.sub.2, 9-CH.sub.2), 1.49-1.45 (m, 2H, 16-CH.sub.2), 1.39-1.34 (m, 4H, 7-CH.sub.2, 10-CH.sub.2) ppm.

(17) .sup.13C NMR (100 MHz, CDCl.sub.3) (major isomer): 200.4 (s, 1-CO), 139.2 (d, 14-CH), 138.6 (s, 13-C), 137.5 (d, 4-CH), 114.7 (t, 5=CH.sub.2), 40.4 (s, 11-C), 38.0 (2t, 7-CH.sub.2, 10-CH.sub.2), 36.2 (t, 2-CH.sub.2), 35.2 (t, 12-CH.sub.2), 32.7 (t, 16-CH.sub.2), 28.6 (t, 3-CH.sub.2), 24.6 (t, 15-CH.sub.2), 24.2 (2t, 8-CH.sub.2, 9-CH.sub.2) ppm.

(18) ##STR00011##

(19) .sup.1H NMR (400 MHz, CDCl.sub.3) (minor isomer): 6.62 (t, 1H, J=1.5 Hz, 12-CH), 5.89-5.78 (m, 1H, 4-CH), 5.07-5.00 (m, 1H, 5=CH.sub.a), 4.98-4.94 (m, 1H, 5=CH.sub.b), 2.74 (t, J=7.8 2H, 2-CH.sub.2), 2.38-2.32 (m, 2H, 3-CH.sub.2), 2.19 (td, J=6.4, 1.7 Hz, 2H, 14-CH.sub.2), 1.74-1.71 (m, 4H, 8-CH.sub.2, 9-CH.sub.2), 1.67-1.51 (m, 6H, 7-CH.sub.2, 10-CH.sub.2, 15-CH.sub.2), 1.49-1.45 (m, 2H, 16-CH.sub.2) ppm.

(20) .sup.13C NMR (100 MHz, CDCl.sub.3) (minor isomer): 200.6 (s, 1-CO), 148.3 (d, 12-CH), 137.6 (d, 4-CH), 136.6 (s, 13-C), 114.7 (t, 5-CH.sub.2), 44.1 (s, 11-C), 39.9 (2t, 7-CH.sub.2, 10-CH.sub.2), 36.1 (t, 2-CH.sub.2), 34.2 (t, 16-CH.sub.2), 28.5 (t, 3-CH.sub.2), 24.5 (2t, 8-CH.sub.2, 9-CH.sub.2), 23.3 (t, 14-CH.sub.2), 20.0 (t, 15-CH.sub.2) ppm.