DE1134784B - Fragrance - Google Patents

Description

Fragrance odorous substances of the ambratyp (amtier type) are important Substances in the perfume industry.

Exact examination of the degradation of natural ambergris and similar products by M. S to 11 and coworkers (Industries de la parfumerie, 9 [1954], 4 and 48) and by E. Lederer and coworkers (Industries de la parfumerie, 8 [1953]) , 189 and 12 [1957], 231) have led to the discovery of a number of compounds with an ambrage odor in recent years. I to III are mentioned as examples. However, all of the Ambrav connections now known are only accessible by means of relatively complicated processes using natural products as the starting material.

The present invention seeks to manufacture a number of Compounds with odor of the ambratype made in a simple way, starting from light cheap substances available.

The condensation of myrcene (IV) with maleic anhydride (V) and subsequent cyclization (VI), reduction (VII), cyclization and hydrogenation leads to the formation of a tricyclic ether (IX) with a woody odor, which, however, has no amber character. It has now been found that the introduction of one or two methyl groups into compounds of type IX causes a shift in the odor character and produces a certain and often strong adherent ambrage odor. Methyl homologues of the unsaturated ether VIII also often show an ambrage odor, which, however, is much weaker than that of the saturated compounds. This is surprising since many cases are known in which the disappearance of one or more double bonds either reduces the odor properties or does not affect them. In the series of compounds with an ambrage odor, this is the case with X, because the ambrage odor practically disappears when the double bond is hydrogenated (M. Stoll and M. Hinder, Helvetica Chimica Acta, 33, 1251 [1950]), while the odor of XI remains unchanged when the double bond is reduced (L. Ruzicka and CF Seidel, Helvetica, 33, 1285 [1950]). The aim of the present invention is to develop new ambrate-type odor compounds of the general formula XII wherein the substituents R are either both methyl groups or a methyl group and 1 hydrogen atom.

By far the strongest Ambrag odor is obtained when one of the Substituents R is a methyl group and the other is a hydrogen atom.

Type XII compounds are easily obtained by cyclizing a diol of type XIII accessible, where R has the meaning mentioned above. Such cyclizations can conveniently be effected by a suitable dehydrating agent, such as z. B. aryl or alkanesulfonic acids, sulfuric acid, phosphoric acid, oxalic acid, maleic anhydride or similar anhydrides, potassium hydrogen sulfate or similar acidic salts, aluminum oxide, Chromium oxide, silica or alum in the liquid as well as in the vapor phase. One a large number of such reagents have been reported by W. Reppe and others (Annalen, 596 [1955], 81). Useful results can also be obtained by indirect cyclization methods, z. B. by treating the corresponding dihalide with magnesium hydroxide L. Schmerling and J. P. West (J.A.C.S., 74 [1952], 2885), by eliminating Sulphonic acid from the corresponding monosulphonate using pyridine or lutidine Reynolds and Kenyon (J.A.C.S., 72 [1950], 1953) or by elimination of methyl bromide from an ether of the corresponding bromohydrin using iron chloride according to A. Kirrmann and N. Hamaide (Bull. Soc. Chimique France 1957, 798).

A second cheap method of making ethers of the type XII is the cyclization of unsaturated diols of type XIV according to one of the above-mentioned Process and subsequent hydrogenation of the double bond.

Diols of the types XIII and XIV, in which R has the meaning mentioned above, can conveniently be prepared by condensation of myrcene with either citraconic anhydride or with pyrocinchonic anhydride, followed by cyclization and reduction steps, the sequence of which is of little importance. Other inexpensive starting products are lactones of type XVII and XVIII, which can also be conveniently prepared from myrcene.

Both types of intermediates can be converted to diols of types XIII and XIV in 1 to 3 steps, which is illustrated by the following reaction scheme (the groups R are either both methyl or hydrogen and methyl groups). In some of the steps indicated, regardless of which reaction sequence is chosen, more than 1 isomer is formed. The isomers have two causes.

1. The position of the methyl group when a substituent R is hydrogen is.

2. Conformation factors. Because the end product is three saturated rings contains a number of conformational isomers are possible.

It is therefore inevitable that it will do after one of the above The product obtained from reaction sequences consists of a certain number of isomers; but since even by distillation in powerful columns it is not a complete one Separation is possible and since such distillation gives fractions of which all show the typical smell of Ambrag, such a distillation is not practical Value. However, it is possible by using pure isomers or stereoisomers of intermediate products as starting material are pure isomers or stereoisomers of to obtain Ambrav connections disclosed here.

Several such isomers or stereoisomers have thus been obtained from some of which are described in the examples. It was found that the different isomers or stereoisomers do not all have Ambrage odors with the same intensity to have. The invention is illustrated by the following examples.

Unless otherwise stated, the melting points are corrected, the boiling points not corrected. All structures are supported by elemental analysis. The addition a relates to products in which R = hydrogen 'and methyl, the addition b to those in which both R = methyl groups.

Example 1 224 g (2 moles) of citraconic anhydride in dry xylene are heated to reflux temperature (150 ° C), and 327 g of redistilled commercial myrcene (which contains about 1.9 moles of pure myrcene) are added dropwise over the course of 25 minutes added while maintaining refluxing without external heating. The mixture is stirred for another hour at reflux temperature, which ends at the end this period is 170 ° C.

After fractionation through a column of 16 theoretical plates the adduct XV is obtained in 90% yield (calculated on myrcene), boiling point 114 up to 117 ° C at 0.01 mm; nö (const.) 1.4950.

The product undoubtedly consists of more than one isomer and / or Stereoisomer, as evidenced by the inconsistent relative densities and relative viscosities is shown in fractionation. A Component is made by means of of the tetrabromide C15H2003Br4 with the F. 149.7 to 150.5'C.

248 g (1 mol) of adduct XV in 248 g of dry benzene are mixed with 25 g (0.18 mol) boron trifluoride etherate 1 hour and 20 minutes at 80 to 81'C (reflux) heated. After removal of the catalyst and the solvent, the is formed tricyclic dicarboxylic anhydride XIXa fractionated in vacuo, with 87% of the Theory obtained on a product from bp 154 to 157 ° C at 0.8 mm, no 1.506 to 1.509 will. This substance partially crystallizes on standing, and is a pure isomer from 150.4 to 150.7'C can be isolated (see Example 4).

25 g (0.65 mol) of lithium aluminum hydride are refluxed in 300 ml heated dry ether suspended in a nitrogen atmosphere, and over the course of A solution of 107 g (0.43 mol) of anhydride XI, Xa in 450 ml of dry ether was added dropwise at such a rate that without external heating the refluxing is maintained. The reaction mixture is refluxed with stirring for a further 21/2 hours and then worked up.

The diol XIVa is obtained as a viscous oil (mixture of isomers and / or stereoisomers) which is used without purification. Yield 90 ° / o, n ö ° (approximately) 1.516 to 1.519.

558 g (2.4 mol) of this mixture of diol isomers are in 1350 ml dissolved in dry benzene, 11 g of p-toluenesulfonic acid are added and the mixture is refluxed using a Dean-Stark trap, until no more water separates. After 15 hours there was 39.5 g of water (about 90 ° / a of theory) collected in the device.

The reaction mixture is worked up and in vacuo by a Fractional column of 16 theoretical plates. Trimethyl decahydronaphthofuran (2,3-c) XXa is obtained as a mixture of isomers and stereoisomers and has a Boiling range from 74 to 80'C at 0.05 mm, tzö 1.502 to 1.510. All fractions have a characteristic, but relatively faint, ambra-type odor.

Similar results are obtained when 18 g (0.075 moles) of the same Diol XIXa with 250 g aqueous sulfuric acid (200 /, vol / vol) at 108'C for 4 hours be treated.

133 g (0.6 mol) of the unsaturated ether XXa are hydrogenated in a stainless steel shaking autoclave in isopropanol as the solvent, Raney nickel serving as the catalyst and an initial pressure of 77 at (1100 psi) at 125.degree. The calculated amount of hydrogen will be absorbed in about 15 hours. At 105 at (1500 psi) and 200 ° C., the hydrogenation is complete in 10 hours.

The product is worked up and passed through a column of 28 theoretical Soils fractionated. Trimethyldodecahydronaphthofuran (2,3-c) XIIa, from the boiling range 100 to 110 ° C at 0.25 mm, n 'D' 1.495 to 1.500 is obtained in 96% yield.

All fractions have a strong and adherent ambrag odor.

The complete mixture shows the following constants nö ° 1.4980, d1 ° 0.9816. Gas-liquid phase chromatographic analysis shows the presence of at least 7 components, 4 of which are in small quantities (less than 5111, of the overall mixture), and 3 of these are main components, A, B and C, the make up about 27, 42 and 18% of the total mixture.

In the case of a number of fractions from the above-mentioned fractionation (Column of 28 trays) with bp 101 to 102 ° C at 0.3 mm, n ö 1.4990, the main component occurs A with about 70 ° / a, and at least four smaller maxima are closed in the chromatogram see. The main component B is in a number of fractions with bp 106 bis 107'C at 0.3 mm, nö 1.4950 enriched. These fractions contain about 85 ° / o of isomer B, which is in crystalline form with F.49.2 to 50.0'C by recrystallization can be isolated from acetone at low temperatures. Example 2 850 g (3.6 Mol) of a mixture of the lactones XV11a and XVIIIa are 340 g (14.8 gram atoms) finely divided sodium in 1800 g of toluene and 1150 g (8.7 mol) of diisobutyl carbinol 41/2 Treated hours at reflux temperature (110 to 115'C). After working up will a 90% yield of a mixture of isomers of the diol XIII a as viscous Oil (hydroxyl sample 80%) obtained, which is used without purification.

1080 g (4.5 mol) of diol mixture and 100 g of potassium hydrogen sulfate are used slowly heated to 150'C in a vacuum of 25 mm Hg, with water in a cold trap is collected. After one hour, the distillation of water is complete (65 ml, 80% water is collected).

The pressure is lowered to 3 mm Hg and the product is rapidly distilled (flash distilled); Residue 220 g. The substance obtained has a residual hydroxyl sample of 0.2% and is fractionated by a Vigreux column of 28 theoretical plates. A mixture of isomers and stereoisomers of trimethyl-dodecahydronaphthofuran (2,3-c) XIIa, boiling range 94 to 103'C at 0.2 mm, nr '1.4990 to 1.4967 to 1.5000, is obtained in 91% yield. The total mixture has no 1.4986, d? 0 ° 0.9824 and shows a strong and persistent ambrage odor.

Exactly the same results are obtained with the elimination of water with the aid of p-toluenesulfonic acid as a catalyst in refluxed benzene is carried out according to the method described in Example 1, or by the Vapors diluted with dry nitrogen, at a pressure of 10 to 20 mm a horizontal pipe is passed, which is partially filled with 25 g of activated aluminum oxide filled and to a temperature of 260 to 280'C by means of an electric oven is heated. Gas-liquid phase chromatographic analysis of the complete mixture shows the presence of at least 7 components, probably all of which are identical to those described in Example 1, but in somewhat different ways Relationship. The four minor components together contain about 22% Mixture, the three main ingredients A, B and C occur in amounts of about 32, 28 or 18%.

In a series of fractions from the above-mentioned fractionation from bp 94 to 96 ° C. at 0.2 mm, no (const.) 1.4990, component A occurs with about 70 % , and at least 4 smaller maxima are in the chromatogram evident.

Component B is in a group of fractions from bp 100 to 101'C at 0.2 mm, not 1.4968, enriched, of which it forms about 70%. He can by Recrystallize from acetone to be isolated, a crystalline isomer of F. 49.1 to 49.9'C is obtained, which turns out to be identical to the corresponding, material described in Example 1 proves (no mixed melting point depression).

Example 3 From the adduct of myrcene and citraconic anhydride XV, that was obtained according to Example 1 can be a dicarboxylic acid with a melting point of 127.8 to 128.3 ° C isolated by repeated crystallizations from aqueous acetic acid.

By treating this acid with boron trifluoride etherate on the im Example 1 described type is the corresponding bicyclic dicarboxylic acid from M.p. 218 to 222 ° C (uncorrected) obtained in a relatively low yield.

The same compound is obtained in 53% yield when 42g (0.16 mol) adduct XV was heated under reflux for 15 hours with 200 ml of 20% hydrochloric acid will. After recrystallization from ethyl acetate, a pure compound is Mp 224.8 to 225.5 ° C. When mixing with the one in the previous section no depression will be obtained.

The same compound is also obtained when 62 g (0.25 mol) of tricyclic Anhydride XIX a is heated under reflux for 15 hours with 300 ml of 20% hydrochloric acid will. A product with a melting point of 224.6 to 225.5 ° C. is obtained in 64 ° / @ ger yield is identical to that described above.

By reduction with lithium aluminum hydride according to the example 1, but in tetrahydrofuran as the solvent, the bicyclic Dicarboxylic acid converted into the corresponding diol XIVa, which as a viscous oil in practically quantitative yield is obtained. From this substance can be a pure one Isomer with a melting point of 112.4 to 112.8 ° C can be isolated.

2.7 g of this crystalline diol are mixed with 0.27 g of potassium hydrogen sulfate, as described in Example 2, heated. After working up it becomes trimethyldecahydronaphthofuran (2,3-c) XXa obtained from 57.9 to 58.9 ° C. This isomer is practically odorless.

The crystalline, unsaturated ether cannot work with Adams' catalyst easily hydrogenated above atmospheric pressure, but after treatment with hydrogen at an initial pressure of 98 at (1400 psi) at 160 ° C in a shaking autoclave made of stainless steel with ruthenium on carbon as a catalyst over the course of 6 hours trimethyl-dodecahydronaphthofuran (2,3-c) is obtained with a melting point of 49.7 to 50.2 ° C, that is identical to the corresponding compound described in Examples 1 and 2 is. This connection has a pronounced amber odor. Example 4 From the tricyclic anhydride XIXa, which was obtained according to Example 1, can be a crystalline Isomer from 150.4 to 150.7 ° C can be isolated. After recrystallization from aqueous Acetic acid is the corresponding bicyclic dicarboxylic acid with a melting point of 190.8 to 192.5 ° C (with decomposition) obtained.

7.5 g (0.03 mol) of crystalline anhydride XIXa in 25 ml of tetrahydrofuran slowly become a refluxed solution of 1.7 g lithium aluminum hydride added in 20 ml of tetrahydrofuran. After refluxing for 61/2 hours the mixture worked up. In practically quantitative yield it becomes a crystalline one Diol XIVa obtained from m.p. 123.6 to 124.3'C.

3 g (0.012 mol) of this diol are treated with 0.3 g of potassium hydrogen sulfate, as described in Example 2, dehydrated. In a practically quantitative way Yield obtained trimethyldecahydronaphthofuran (2,3-c) XXa has the F. 67.4 bis 67.9 ° C.

1 g (4.5 mmol) of crystalline, unsaturated ether is dissolved in acetic acid at room temperature over 0.15 g of Adams catalyst at a pressure slightly above atmospheric pressure hydrogenated. The trimethyldodecahydronaphthofuran (2,3-c) XIIa, which in practically quantitative Yield obtained is crystalline, already in Examples 1, 2 and 3 isomer of mp 49.2 to 50.0'C. Example 5 From the mixture of isomers of the lactone of structure XVII a and XVIII a can be a crystalline isomer of F. 162.0 to 162.4 ° C.

5 g (0.02 mol) of this crystalline lactone are in the corresponding Diol by treatment with 0.62 g (0.016 mol) of lithium aluminum hydride in 30 ml of tetrahydrofuran converted at reflux temperature over 5 hours. After the usual work-up a crystalline substance was obtained in quantitative yield. The pure connection had a mp of 77.8 to 78.7 ° C, and elemental analysis showed that it was a complex of a diol of structure XIII a with tetrahydrofuran (1: 1 molar ratio).

4 g of crude diol-tetrahydrofuran complex were mixed with 0.4 g of potassium hydrogen sulfate, as described in Example 2, heated. The oily substance thus obtained solidified when cooling in an acetone-dry ice mixture. After recrystallization from acetone it showed a temperature of 40.7 to 41.4 ° C (considerable depression when mixing with the compound with a temperature of 49.2 to 50.0 ° C). The new connection has a strong one and persistent ambrage odor. Example 6 In the saponification of 60 g (0.24 moles) of adduct XV with 200 ml of 10% sodium hydroxide in the course of one hour at reflux temperature, Working up in the usual way and recrystallization of the product from 1-nitropropane, Ethyl formate and acrylonitrile is a pure isomer of the corresponding Dicarboxylic acid with a melting point of 140.7 to 141.7 ° C.

By treating this dicarboxylic acid with boron trifluoride etherate according to the method described in Example 1 is a tricyclic anhydride XIXa from M.p. 102.1 to 103.1'C.

The same tricyclic anhydride is obtained in the following way: 125 g (0.5 mol) of adduct XV are dissolved in 125 g of dry benzene and this solution is cooled to -5 ° C. A slow stream of boron trifluoride is introduced from a cylinder. After several minutes, the reaction begins suddenly and the temperature rises to 45 ° C. The introduction of BF3 is interrupted to allow the mixture to cool to 25 ° C and then resumed until the mixture is saturated, the total weight gain being 24.5 g. The mixture is stirred for a further 2 hours at room temperature, water is added and the mixture is treated in the usual way. The crystalline isomer of the tricyclic anhydride XIX a with a melting point of 102 to 103 ° C. is obtained in about 70% yield.

The tricyclic anhydride XIXa is made using lithium aluminum hydride reduced in tetrahydrofuran according to Example 4, a crystalline diol XIVa is obtained from the F. 92.6 to 93.1'C in practically quantitative yield.

1.5 g of this diol are obtained by heating with potassium hydrogen sulfate dehydrated according to the procedure described in Example 2. The trimethyldecahydronaphthofuran (2,3-c) XXa, which is obtained in quantitative yield, shows no 1.5001.

The unsaturated ether obtained in this way is treated with Adams catalyst in Acetic acid hydrogenated at room temperature. The hydrogenation is complete in 111/2 hours. After removing the solvent, the trimethyl-dodecahydronaphthofuran (2,3-c) XIIa obtained as an oil, n '£)' 1.4960.

Gas-liquid phase chromatographic analysis of this oil shows the presence of at least four of the isomers referred to in Examples 1 and 2. The main constituent, which is different from constituents A, B and C of the mixtures indicated in the aforementioned examples, makes up about 600 % of the total mixture. Example 7 163 g (1.2 mol) of commercial myrcene are heated with 126 g (1 mol) of pyrocinchonic anhydride in 100 g of propionic acid at 143 ° C. for 16 hours. The reaction product is purified by distillation. About 50 grams of pyrocinchonic anhydride is recovered and a product of structure XVI is obtained in almost quantitative yield. The bp is 114 to 117 ° C at 0.05 mm; n 2D0 (const.) 1.4933.

209 g (0.8 mol) of compound XVI are combined with 20 g (0.14 mol) of boron trifluoride ether complex refluxed in 200 g of dry benzene for 2 hours. The anhydride XIXb is obtained as a viscous oil which partially solidifies on standing. The yield is 90% of theory. The crystalline isomer has a mp of 90.1 to 90.7 ° C.

145 g (0.55 mol) of the tricyclic anhydride XIXb are treated according to Example 1 with 42 g (1.1 mol) of lithium aluminum hydride in 400 ml of dry ether without prior purification. The diol of structure XIV b, a mixture of isomers and stereoisomers, is obtained as a viscous oil . Yield 98% of theory. A pure isomer with a melting point of 126.8 to 127.5 ° C. can be isolated.

139 g (0.55 mol) of diol XIVb are dissolved in 150 ml of dry benzene with 3 g p-toluenesulfonic acid with continuous azeotropic removal of the during the Reaction formed water heated under reflux until no more water is accumulates. The reaction product is worked up and passed through a column with 16 theoretical soils fractionated.

93 g (73% of theory) of the fractions from the boiling range 92 to 106 ° C at 0.2 mm, n 2D "1.5007 to 1.5096, all of which have ambra-type odor obtain.

The through elemental analysis of the beginning, main and ending parts of these Values obtained from fractionation agree well with those for tetramethyldecahydronaphthofuran (2,3-c). The product is undoubtedly a mixture of isomers.

90 g (0.38 mol) of this mixture are dissolved in 400 ml of isopropyl alcohol and dissolved in a stainless steel shaking autoclave in the presence of Raney nickel hydrogenated at an initial pressure of 130 at (1850 y) at 205 ° C.

The reaction mixture is worked up and the product becomes again carefully fractionated. Tetramethyldodecahydronaphthofuran (2,3-c) XIIb, b.p. 120 up to 124 ° C at 0.6 mm pressure, n0 ° 1.4970 to 1.4990, has a pronounced amber odor, which is weaker but more persistent than that of the trimethyl analogue XII a.

A group of fractions from the above distillation solidified partially. After recrystallization, a pure isomer of structure XIIb isolated from mp 53.1 to 53.7 ° C.

Claims (5)

PATENT CLAIMS: 1. Fragrance composition, characterized by a content of saturated, tricyclic ethers with an amber-like odor of the general formula XII wherein either both symbols R denote methyl groups or one denotes a methyl group and the other denotes a hydrogen atom. 2. fragrance composition according to claim 1, characterized in that one of the two symbols R in the formula XII represents a methyl group and one represents a hydrogen atom and the compound has an approximate melting point of 49 to 50 ° C. 3. fragrance composition according to claim 1, characterized in that one of the symbols R in the formula XII represents a methyl group and one represents a hydrogen atom and the approximate melting point is 41'C. 4. fragrance composition according to claim 1 to 3, characterized in that it contains such saturated tricyclic ethers as an effective component, the cyclization of saturated bicyclic diols of the general formula in which R has the meaning given, have been obtained in the presence of an acidic catalyst. 5. fragrance composition according to claim 1 to 3, characterized in that it contains such saturated tricyclic ethers as an effective component, which by cyclization of unsaturated bicyclic diols of the general formula in which R has the meaning mentioned, have been obtained in the presence of an acidic catalyst and subsequent hydrogenation of the double bonds.