DE2410859A1 - Macrocyclic ketolactone musk perfume prepn. - from oxa- bicycloalkenes by ozonolysis - Google Patents

Abstract

Macrocyclic ketolactones (II) are prepd. by ozonolysis of oxabicycloalkenes of formula (I): (where R1, R2 and R3 are H, Me or Et; n is 9-13 and m and p are O or 1). (II) are known as strong, pleasant musk perfumes and can also be converted to unsubtds, macrocylic lactones, useful in perfumery.

Description

Macrocyclic Ketolactones The present invention relates to a Process for the preparation of macrocyclic ketolactones from oxabicycloalkenes.

Macrocyclic ketolactones are used as intense and pleasant musk fragrances known (Ohloff, Advances in Chem. Research 12, 203 (1969)).

A process for the preparation of macrocyclic ketolactones has been found which is characterized in that oxabicycloalkenes of the general formula I. in which R1, R2 or R3 are identical or different and represent an H atom or a methyl or an ethyl radical, n represents an integer from 9 to 13 and m and p are identical or different and represent the numbers 0 or 1, subjected to ozonolysis.

As oxabicycloalkenes, which are preferred according to the invention Find methods of use, those for which in general are mentioned Formula I n stands for 9 or 10, where m, p, R1, R2 have the aforementioned scope and m and p are not both zero.

Compounds of the general formula I in are particularly preferred which n stands for 10, m stands for 1 and p stands for 0 or 1, where for the case that p is 0, R1 and R2 are identical or different and are hydrogen or den Methylres-t stand and, in the event that p stands for 1, R1, R2 and R3 stand for hydrogen stand.

The ozonolysis according to the method according to the invention is expediently carried out by putting the oxabicycloalkenes in an organic or inorganic solvent dissolves or

suspended and in the solution or suspension at a temperature introduces ozone from approx. 0 to 60 0C. Appropriately find the solvent as the solvents commonly used in ozonolysis, such as acetic acid, methanol, ethanol, Butanol, hydrocarbons such as cyclohexane or gasoline, chlorinated. Hydrocarbons , Water or aqueous saline solution use.

The reaction temperatures for ozonolysis are in general between -20 and 60 ° C, preferably between 0 and 40 ° C, particularly preferably between 10 and 3000. In general, the reaction is carried out at normal pressure.

The ozonides formed as intermediates during ozonization are in hydrolyzed in a known manner. For example, the reaction mixture can through Heating in aqueous or aqueous-alkaline solution converted into the ketol catones will. Hydrolysis has proven to be particularly advantageous under reducing conditions, proved, for example, with an aqueous sodium hydrogen sulfite solution. The separation the ketolactones formed can by known methods, for example by distillation take place.

As oxabicycloalkenes, which by the process according to the invention Use can be mentioned, for example: 12-0xa-bicyclo / 9.3, o7tetradecen-1 (11), 1 2-Oxa-1 3-methylbicyclo [9.3.0] tetradecene-1 (11), 12-Oxa-bicyclo [9.4.0] pentadecene-1 (11), 12-Oxa-13-methyl-bicyclo [9.4.0] pentadecene-1 (11) 12-Oxa-14-methyl-bicyclo [9.4.0] pentadecene-1 (11), 12-Oxabicyhclo [9.5.0] hexadecen-1 (11), 13-Oxa-bicyclo [10.3.0] pentadecen-1 (12), 13-oxa-14-methyl-bicyclo50.3.07 pentadecene-1 (12), 13-oxa-bicyclo [10.4.0] hexadecene-1 (12), 13-Oxa-14-methyl-bicyclo [10.4.0] hexadecene-1 (12), 13-oxa-15-methyl-bicyclo [10.4.0] hwxadecen-1 (12), 13-oxa-14,15-dimethyl-bicycloz10.4.07hexadecen-1 (12), 13-oxa-14-ethyl-bicyclo50.4.07hexadecen-1 (12), 13-oxa-15-ethyl-bicyclo [10.4.0] hexadecene-1 (12), 13-oxa-bicyclo- [10.5.0] -heptadecene-1 (12), 13-Oxa-16-methyl-bicyclo- [10.5.0] -heptadecene-1 (12), 14-oxa-bicyclo [11.3.0] hexadecene-1 (13).

14-Oxa-bicyclo [11.4.0] heptadecen-1 (13), 14-Oxa-15-methylbicycloz 11.3.07hexadecen-1 (13), 14-OIa-15-methyl-bicyclo [11.4.0] heptadecene-1 (13), 14-oxa-16-methyl-bicyclo [11.4.0] heptadecene + d1 (13), 15-oxa-bicyclo [12.3.0] heptadecene-1 (14), 15-oxa-bicyclo [12.4.0] o @ tadecen-1 (14), 16-oxa-bicyclo [13.3.0] oxtadecen-1 (15), or 16-oxa-bicyclo [13.4.0] nonadecene 1 (15).

The following may be mentioned as preferred: 13-Oxa-bicyclo [10.3.0] pentadecene-1 (12), 13-Osa-14-methyl-bicycloZ10.3.07 pentadecene-1 (12), 13-oxa-bicyclo [10.4.0] hexadecene-1 (12), 13-oxa-14-methylbicyclo [10.4.0] hexadecene-1 (12), 13-Oxa-15-methyl-bicyclo [10.4.0] hexadecene-1 (12), 13-oxa-14, 15-dimethyl-bicyclo [10.4.0] hexadecene-1 (12), 13-oxa-14-ethyl-bicyclo [10.4.0] hexadecene-1 (12), 13-oxa-15-ethyl-bicyclo [10.4.0] hexadecene-1 (12), 13-oxa-bicyclo- [10.5.0] heptadecene-1 (12), 13-oxa-16-bicyclot50.5.07heptadecene-1 (12); particularly preferably 13-oxabicyclo [10.4.0] hexadecend-1 (12), 13-dOxa-14-methyl-bicyclo [10.4.0] hexadecene-1 (12), 13-oxa-15-methyl-bicyclo [10.4.0] hexadecend-1 (12) d, 13-oxa-bicyclo [10.5.0] hexadecene-1 (12) .

The oxabicycloalkenes used as starting material are known and can be produced by known processes (DOS 2 136 496, DOS 2 026 056).

Accordingly, as ketolactones, which according to the invention Process can be produced, for example mentioned: 11-oxo-tridecanolide, 11-oxo-13-methyl-tridecanolide, 11-oxotetradecanolide, 11-oxo-14-methvl-tetradecanolide, 11-oxo-13-methyl-tetradecanolide, 11-oxo-13-methyl-tetradecanolide, 11-oxo-pentadecanolide. 1 1-oxo-pentadecanolide, 12-oxo-tetradecanolide, 12-oxo-14-methyl-tetradecanolide, 12-oxo-pentadecanolide, 12-oxo-14-methyl-pentadecanolide, 12-oxo-15-methyl-pentadecanolide, 12-oxo-14, 15-dimethylpentadecanolide, 12-oxo-14-ethyl-pentadecanolide, 12-oxo-15-ethyl-pentadecanolide, 12-oxo-hexadecanolide, 1 2-oxo-14-methyl-hexadecanolide, 1 3-oxo-pentadecanolide, 1 3-oxo-hexadecanolide, 13-oxo-16-methyl-hexadecanolide, 13-oxo-15-methyl-hexadecanolide, 14-oxo-hexadecanolide, 14-oxoheptadecanolide, 15-oxo-heptadecanolide, 15-oxo-octadecanolide.

The ozonylation according to the method according to the invention can be used, for example, in the Way to be carried out that the solution or suspension of the Oxäbicycloalkens in a reaction vessel equipped with a stirrer with stirring at the corresponding Reaction temperature with ozone. Generally, the ozone comes in the form of a Ozone-air mixture used with a share of approx. 1.5% ozone.

Nacrocyclic ketolactones are used as intense and pleasant musk fragrances known (Ohloff advances in previous research, Springer-Verlag, Heidelberg 1969, Vol. 12, Issue 2, Page 203). Eetolactones can also be prepared using known methods into the unsubstituted macrocyclic lactones, which are very valuable in perfumery, such as e.g. Exaltolid.

The ketolactones obtained by the process according to the invention represent Musk fragrances, they can be used with advantage in odoriferous substances will.

Example 1 223 g of 13-oxa-bicyclo [10.4.0] -hexadecene-1 (12) were in 1000 g of acetic acid dissolved and in a stirred vessel with a tubular stirrer at 20 ° C with 48 g of ozone (1.5% in air) converted. After decomposition of the ozonides formed with 230 The solution of the reaction products became g of a 40% aqueous sodium hydrogen sulfite solution filtered and concentrated, taken up in gasoline and washed neutral. One steamed the solvent off, the residue was distilled on a thin film evaporator (18000, Torr) and received a crude product which was fractionally distilled the following fractions were obtained: 14 g KP0.2 110-14000 mostly unreacted Starting product 112 g bp 0.2 140 - 145 ° C 12-oxo-pentadecanolide (approx. 98%) 27 g KP0.2 145-165 8 g residue The 12-o-pentadecanolide was recrystallized from methanol (Mp 32.5-33,000) Odor: musk grains Example 2 A suspension of 222 g of 13-oxa-bicyclo [10.4.0] -hexadecen-1 (12) in 800 g of a 7.5 algae aqueous solution Sodium hydrogen carbonate solution at 25 - 30 ° C with vigorous stirring with 48 g of ozone (1.5% in air), added gasoline, separated the organic phase and decomposed the ozonides with the amount of sodium hydrogen sulfite calculated on the residual peroxide content (generally 10-20 g). The product was washed neutral and as in example 1 worked up.

192 g of crude product were obtained, from which fractionated by Distillation 148 g of 12-oxo-pentadecanolide were isolated.

Example 3 Batch quantities and implementation as in Example 2, with the The difference is that distilled water is used instead of the hydrogen carbonate solution became. The aqueous suspension was then refluxed for 2 hours, the remaining ozonides were largely destroyed, separated after the addition of little gasoline and distilled the product.

185 g of crude product were obtained, from which by fractional distillation 124 g of 12-oxo-pentadecanolide were isolated (38 g of starting product were recovered.) Example 4 A solution of 111 g of 13-oxabicyclo [10.4.0] -hexadecene-1 (12) in 500 ml At 1000, n-butanol was reacted with 24 g of ozone (1.5% in air). The reaction solution was refluxed for 2 hours and distilled. 94 g of a fraction were obtained of boiling point Kp1 110 - -i700C and 22 g of residue.

By gas chromatographic analysis, about 90% of 12-oxopentadecanolide was found in the distillate proven.

Similar results were obtained e.g. B. ozonolysis in methanol or Ethanol.

Example 5 A suspension of 52 g of 12-0xa-bicyclolg. 4. 07-pentadecene-1 (11), in 250 g of 7.5 pointer sodium hydrogen carbonate solution was stirred vigorously reacted at 30 ° C with 12 g of ozone (1.5% in air). The reaction mixture was thereafter Heated under reflux for 30 minutes, the oil formed was taken up in gasoline and the organic phase washed neutral and distilled. In addition to unreacted starting material and higher-boiling fractions were 25 g of 11-oso-tetradecanolide, b.p. 0.5 135-13600 won. The product was recrystallized from methanol (mp 43.5-4400).

Odor: musk grains Example 6 The ozonolysis of 59 g of 13-0xa-14-methyl-bicyclo / T0.4.07-hexadecen-1 (12) was carried out analogously to Example 5. In addition to 14 g of unreacted starting material, 25 g 12-oxo-15-methyl-pentadecenolide, bp 0.5 128 ° C Odor: musk with sandal example 7 100 g of 13-oxa-15-methyl-bicyclo50.4.07-hexadecene-1 (12) were stirred vigorously in 500 g of 7.5% sodium hydrogen carbonate solution at 30 ° C with 20.5 g of ozone (in Air) implemented.

The product obtained was taken up in gasoline and destroyed the remaining Ozonide.mit 24 g of 40% sodium hydrogen sulfite solution, washed; neutral and distilled.Man recovered 22 g of starting material and obtained 45 g of 12-oxo-14-methyl-pentadecanolide, which distilled at 127-13,000 1 0.05 torr. After recrystallization from methanol obtained melting point 43-43,500. Odor: musk with sandel. Example 8 Analogous to Example 7 100 g of 13-oxa-bicyclo [10.5.0] -heptadecene-1 (12) were reacted. The distillation of the reaction product yielded: 21 g of starting material and 36 g of 12-oxo-hexadecanolide Bp 0.2: 149-151 ° C; nD20 = 1.4815; D420 = 1.010 Example 9 - 12 Analogous to Example 7 were obtained by ozonolysis of the starting materials mentioned in line 1 of Table 1 below obtained the ketolactones listed in line 2, their physical and olfactory properties Properties are summarized in Table 1.

Table 1 Kp 20 20 Input material end product (xetolactone) MP (° C) ° C / nn Hg D 4 nD smell 13-Oxo-16-methyl-bicyclo- 12-Oxo-14-methyl- - 158 - musk. [10.5.0] -heptadecen-1 (12) heradecanolide 160 / 0.4 1,000 1.4800 fat. 13-Oxa-14-äthyl-bicyclo- 12-Oxo-15-ethyl- 41.5-42.5 148 - feminine [10.4.0] -hexadecene-1 (12) pentadecanolide 150 / 0.2 - - Mosehus.u. 16-Oxa-bicyclo- [13.4.0] - 12-Oxo-octadecanolide - 138 - wood, weak nonadecen-1 (15) pentadecanolide 140 / 0.2 0.998 1.4870 musk with Sandal 16-OXa-bicyclo- [13.4.0] - 15-oxo-octadecanolide - 176-0.964 1.4872 Moeohus, nonadecane-1 (15) 180 / 0.4 fat (very awake)

Claims (8)

Patent claims 1. Process for the preparation of macrocyclic xetolactones, characterized in that oxabicycloalkenes of the general formula I are used in which R1, R2 or R3 are identical or different and represent an H atom or a methyl or ethyl radical, n represents an integer from 9 to 13 and m and p are identical or different and represent the numbers 0 or 1 , subjected to ozonolysis. 2. The method according to claim 1, characterized in that in general Formula n is 9 or 10. 3. The method according to claim 1 and 2, characterized in that m for 1 and p for 0 or 1. 4. The method according to claim 1, characterized in that 13-oxa-bicyclo- [10.3.0] -pentadecen-1 (12), 13-oxa-14-methylbicyclo [10.3.0] -pentadecene-1 (12), 13-oxa-bicyclo [10.4.0] -hexadecene-1 (12), 13-oxa-14-methyl-bicyclo [10.4.0] -hexadecene 1 (12), 13-oxa-15-methyl-bicycloz10.4.07-hexadecene-1 (12), 13-oxa-14,15-dimethyl-bicycloz10.4.07-hexadecene-1 (12), 13-oxa-14-ethyl-bicyclol10.4.07-hexadecene-1 (12), 13-oxa-15-ethyl-bicyclo [10.4.0] -hexadecene-1 (12), 13-oxa-bicyclo- [10.5.0] -heptadecene-1 (12), 13-Oxa-16-methyl-bicyclo [10.5.0] -1 (12) can be used as the starting material. 5. The method according to claim 1, characterized in that i3-0xa-bicyclo / 70.4.07-hexadecene-1 (12) is used as the starting material. 6 The method according to claim 1, characterized in that 13-oxa-14-methyl-bicyclo50.4.07-hexadecene-1 (12) is used as the starting material. 7. The method according to claim 1, characterized in that 13-oxa-15-methyl-bicyclo50.4.Q7-hexadecene-1 (12) is used as the starting material. 8. The method according to claim X, characterized in that 13-0xa-bicycloL70,5,07-heptadecene-i (12) is used as the starting material.