DE2630428B2 - 15-methyl- and 15-ethyl-13-oxo- or -13-hydroxybicyclo [103.0] -pentadecane or -pentadecene- [1 (12)], process for their production and use as odoriferous substances - Google Patents

Description

in the

R 'is - CH ₃ or -C ₂ H ₅ ,

A and B either both stand for H or A and B together form an additional bond between the carbon atoms carrying them mean and

IO

15th

20th

O or

I -H \ —OH

means

2. Process for the preparation of 13-hydroxy- or 13-oxo-bicyclo [103.0] pentadecanes or -pentadecenen- [l (12)] according to claim 1, characterized in that acetylene glycols are used general formula II

OH

OH C = C-CH R ¹

OD

in which R ^{1 has} the meaning given above, in the presence of an acidic catalyst system with an acid strength which is equal to or greater than that of HCOOH or of Lewis acids at temperatures of 50 ^° C. to 200 ° C., preferably 50 ^° C. to 150 ^° C. , heated and in the event that A and B stand for H, the obtained 15-alkyl-13-oxo-bicyclo [103.0] -pentadecacen- {l (l2)] in the presence of Pd, Pt or Ni catalysts hydrogenated or for the

Case that X

f - H I-OH

is the compounds of formula

The invention relates to 15-methyl- or 1 5- ethyl-1 3-oxo- or 13-hydroxy-bieydo- [l0.3.0] pentadecane or pentadecene [1 (12)], which have excellent properties have as musk fragrances, as well as processes for their production by acid-catalyzed rearrangement of certain 1-hydrosyl- [3'-hydroxy-9U «nyl] -cyclododecanes.

It is well known that macrocyclic Mosebus fragrances are such as muscon, cyclopentadecanone, cyclohexadecanone etc. due to their olfactory properties all other known musk fragrances, such as the Superior to tetralin or nitro musk fragrances. There macrocyclic fragrances are difficult to access synthetically and their natural occurrence is limited are, they are extremely expensive and their use is limited to a few luxury items. The demand for olfactory similar but inexpensive compounds is therefore very large.

The object of the invention was therefore a technical one to develop simple and cheap processes for the production of new good musk fragrances.

From the German Auslegeschrift 1668 054 is the Production of 13-oxo-14-methyl-bicycld [i03.0] -pentadecen- [l (12)] as an intermediate for the production Known from Muscon The manufacturing processes described in the cited published publication are, however, technically not very attractive due to the need for numerous reaction stages or the use of poorly accessible and therefore expensive reactants or reagent oils.

It has now surprisingly been found that the new 13-oxo-bicyclo [103.0] pentadecanes or pentadecene {l (12)] of the general formula I.

JO

} 5

40

45

I with X = O with LiAlH ₄ , NaBH ₄ , according to Meewein-Ponndorf with aluminum isopropylate or with nickel and hydrogen.

3. Use of the 13-oxo- or 13-hydroxy-bicyc! O [103.0] -pentadecane or -pentadecene- [l (12)] according to claim 1 as musk fragrances.

in the

R 'is - CH ₃ or - C ₂ Hs,

A and B either both stand for H or A and B together represent an additional bond between mean the carbon atoms carrying them and X = O means

have a very fine and very well adhering musk odor, which is currently the best The compounds of formula 1 with musk fragrances on the market are extraordinarily similar

X ["indicate musky and sandalwood fragrances no-1 - OH

The new 15-methyl- or 15-ethyl-13-oxo- or 13-hydroxy-bicyclo [103.0] -pentadecane or -pentadecene- [l (12)] of the general formula I can be found easy way to prepare by adding acetylene glycols of the general formula Π

OH

OH

C = C-CH

R ¹

in which R 'is -CHi or -C2H5, in the presence of an acidic catalyst system with an acid strength which is equal to or greater than that of HCOOH or of Lewis acids at temperatures of 50 to 200T.

preferably 50 to 150 "C, and in the event that A and B stand for H, the obtained 15 ~ AIkyM3-oxo-bicydo [103 ^> pentadecen- [l (12) 3 in the presence of Pd-, Hydrogenated Pt or Ni catalysts or in the event that

thatX <QjT, the connections of the formula with

X = O with LiAIHt, NaBH ₄ , according to Meerwein-Ponndorf with aluminum isopropylate or with nickel and hydrogen.

As the acetylene glycols have the general formula Π in a simple and known way (see, for example, Helv.Chim. Acta 56 [1973], p. 1503 and Houben-Weyl, "Methods of Organic Chemistry", Volume 4/2 [1955], p.413f) by reacting Cyclododecane ^ with the is Acetylene alcohols of the formula III which are very readily available on an industrial scale

OH HC = CCR ²

(in the

20th

25th

in the presence of bases, such as KOH, NaOCH _3, NaH, NaNHj, CH ₃ MgCl, or basic ion exchangers, at temperatures of -50 KO-tert-CtH9 to + 150 ⁰ C, can be preferably prepared at about 0 ° to 50 ⁰ C. This results in a technically simple and very advantageous synthetic route from the technically readily available cyclododecanone to the new 15-alkyl-IS-oxo-bicycio [103.0] -pentadecene- [l (12)] which are interesting as musk fragrances. The preserved pentadecenes can be converted in a manner known per se by hydrogenation in the presence of Pd, Pt or Ni catalysts into the corresponding pentadecanes, which are also of interest as fragrances with a musky note.

y yy

The connections of the formula with X = {

i - Vj ri

obtained by reduction with LiAlH ₄ , NaBH ₄ , according to Meerwein-Ponndorf with aluminum _{isopropylate or with Ni and H 2} . The 13-hydroxy-bicyclo [103.0] pentadecane or pentadecene [l (12)] obtained have the general formula IV

OH

(IV)

50

55

in the

R ^{1 represents} - CH ₃ or - C ₂ H ₅ and A and B either both stand for H or A and B.

together an additional bond between the protruding carbon atoms obtain.

From the IS-Hydroxy-bicyclotlOJ.Ojpentadecanen or -pentadecenen- [l (l2)] of the general formula IV can by means of esterification processes known per se, -, Ren with lower carboxylic acids, their acid chlorides or their anhydrides, the corresponding carboxylic acid esters are prepared, for. B. is obtained from 13-Hydroxy-l ^ atbyl-bicyclo [103.0] -decen- |: i (12)] and Acetyl chloride the corresponding 13-acetoxy derivative,

Furthermore, the new 13-Qxo-15-methyl-bicyc | o [103.0jpentadecen- [1 (12)] opens up a surprisingly advantageous way of producing the coveted muscone. The production of d, l-muscone from the compound mentioned can be carried out by coaling, ozonolysis, Wolff-Kishner reduction and subsequent decalcifying take place.

The acetylene glycols l-hydroxy-l- [3'-hydroxy-l'- butyn-ryl] -cyclododecane and l-hydroxy-l- [3'-hydroxy-l ^f -pentio-l'-yfj-cydododecane.

Suitable catalysts for the rearrangement of the acetylene glycols of the general formula Π are generally all acids or acidic systems which have an acid strength that is equal to or greater than that of formic acid, i.e. a pKa value equal to or less than about 377 and which do not otherwise attack the parent compound. Examples include: aqueous formic acid in concentrations of 70 to 97%, aqueous sulfuric acid of various concentrations, sulfuric acid diluted with organic solvents such as ethanol, 2-propanol, n-butyl ether and acetic acid, chloroacetic acids, benzenesulfonic acids, strongly acidic cation exchangers such as "Dowex 50" in formic acid or acetic acid, anhydrous oxalic acid, HCl in 2-propanol or dry ether, H ₃ PO ₄ diluted with acetic acid, HCl, in particular HCl in the form of HCl-saturated ether, p-toluenesulphonic acid, phosphorus pentoxide in benzene, KHSO ₄ , MgSO ₄ and NaHSO ₄ , in particular HCOOH, H ₂ SO ₄ , HCi and H ₃ PO ₄ as such, in mixtures with one another or diluted with water or organic solvents such as C 1 to C 2 alcohols, hydrocarbons or ethers such as dioxane, but also Lewis acids like BF ₃ , especially if they are soluble in the reaction mixture.

It is particularly advantageous to use mixtures of acetic acid and concentrated sulfuric acid (proportion by weight of H ₂ SO ₄ about 1 to 10%), since acetic acid is very cheap and also easy to recover

The amount of the acidic catalyst is not critical. It can be between 0.1 and 10 mol, based on 1 mol Acetylene glycol. The use of multiple molar amounts, i. H. so the simultaneous use of the catalyst as a solvent is recommended especially when using aqueous formic acid.

The reaction times are generally between 15 minutes and 3 hours, the reaction temperature is between 50 ° and 200 ⁰ C, preferably between 50 ° and 150 ⁰ C.

The last two parameters mentioned are determined by the type of acid catalyst used. The end point of the reaction can be determined, for example, by thin layer chromatography.

Refer to for further details on this so-called Rupe or Meyer-Schuster rearrangement we on S. Swaminathan et al., Chem. Reviews 71 (1971), 5, pages 429 to 434 and J. Am. Chem. Soc. 75 (1953), 4740.

The reaction mixture is worked up in a customary manner, for. B. by pouring into ice water or Ice, extraction with an inert solvent which is immiscible or only slightly miscible with water and then

ßende distillation, The final purification of the obtained Products can also be obtained by chromatography or crystallization.

The hydrogenation of the 13-oxobicyclo [10J, 0] pentadecene- [l (12)] obtained can be carried out in the presence of Ni, Pd or Pt catalysts with or without a support material, at normal pressure or elevated pressure at temperatures of O ³ to 200 ⁰ C, preferably carried out at 50 ° to 100 "G. As the catalyst carriers are C, SiO _2. AI2O3 or CaCO _3, in particular C is most advantageous considering the pressure bar at about 50 to 100.

The catalyst is generally used in amounts of from 0.1 to 10% by weight. Regarding further For details on this catalytic hydrogenation of a double bond, we refer to G. Schiller in Houben-Weyl, Vol. IV / 2, pages 248 to 303 (1955) and K. Wimmer in Houben-Weyl, Vol. IV / 2, pages 143 bis 152, 163-192 (1955).

example 1 a) Production of the starting material

OH

OH

optionally th acetylene glycol and the reaction mixture for 1 hour at 6O ⁰ C stirred Subsequently, the mixture is poured onto ice and extracted with petroleum ether, the organic phase is neutralized dried and concentrated. 19.8 g of a dark oil remain. Distillation gives 11.2 g of 13-oxo-15-methyl-bicyclo [103.0] -pentadecen- [l (12)] as a light yellow liquid with a boiling point of K _p 0.15 = 123 ° C, which slowly crystallizes, fixed point = 54 to 56 "C, stress te = 57 ¹ Vo of theory, based on the 1-hydroxy-1 - [3'-hydroxy-l'-butyne-1 '-yfj-cyclododecane used. IR, NMR, CirNMR spectra and analysis confirm the structure.

Odor assessment: fine musky odor

Ij ₂₎ When the procedure is as described under 1 b ₍₎ described, but using instead of the mixture of glacial acetic acid and sulfuric acid, 150 ml of 80% formic acid and temperatures of 8O ⁰ C so e / iält to the same result.

From 17 g of Mg turnings into 200 ml of tetrahydrofuran (THF) a Grignard solution is produced with CH3Cl. 24.5 g of 1-butyn-3-ol are added dropwise with cooling After the vigorous evolution of gas has ceased, 57.6 g of cyclododecanone are then added in 150 ml at 0 ° C THF was added dropwise and the reaction mixture was stirred at room temperature overnight

Then it is decomposed with 100 ml of water organic phase separated, dried and concentrated 65 g of a slowly crystallizing remains Oil that according to thin-layer chromatographic investigations from cyclododecanone and a new one Product consists of 25 g of cyclodocyanon are removed by washing with petroleum ether and again recovered. This leaves 34.5 g of a colorless substance with a fixed point of 143 ° C. The spectroscopic data and the analysis confirm the structure of the 1 -hydroxy-1-p'-hydroxy-1 '-butyn-1'-yl] -cyclododecane obtained. Yield 46% of theory, based on Cyclododecanone used and 74% of theory, based on converted cyclododecanone.

bi) According to the invention rearrangement of the acetylene glycol to the bicyclopentadecene

To a mixture of 330 ml of glacial acetic acid and 14 ml of conc. H2SO4 become within 10 minutes at 50 ° up to 60 ° C in portions 21.2 g of the prepared according to la) Example 2 a) Production of the starting material

OH

C = C

56 g of KOH powder are placed in 500 ml of ether. At 0 ^° C., 57.6 g of cyclododecanone and 27 g of l-pentyne-3-o! then added dropwise in 50 ml of ether, the reaction mixture is stirred for 12 hours at room temperature, washed with water, the organic phase is dried and concentrated. 87.7 g of a slowly crystallizing oil remain. After elution of unreacted 23 g cyclododecanone with petroleum ether left 43.6 g of l-hydroxy-l- {3-hydroxy-l-pentyn-l'-YLJ-cyclododecane as a colorless powder from the fixed point 86 to 88 ⁰ C. The yield is 51% of theory, based on the cyclododecanone used, or 89%, based on the cyclododecanone converted.

b)

20 g of the acetylene glycol prepared according to 2a) are orphaned as described in Example Ib) relocated

18.2 g of crude product are obtained. From this, 6.7 g of pure O-oxo-L ^ ethyl-bicyclo [103.0] pentadecene [l (12)] from the fixed point 58 to are obtained by chromatography 60 ° C obtained.

Odor rating _k ^- ng:

fine musky odor, but somewhat weaker than that of the compound prepared according to example lbi).

5.6 g of the 13-0x0-15-methyl-bicyclo- [IC.3.0] -pentadecen- [l (l2)] obtained according to example lbi) are hydrogenated in 150 ml of methanol in the presence of 0.2 g of Pd / C.

After filtration and removal of the solvent, 13-oxo-15-methyl-bicyclo [! 0.3.0] pentadecane remains as a colorless oil, which is distilled on a short-path still, η = 1.4948. The IR spectrum shows that the double bond is quantitatively hydrogenated.

Odor assessment:

fine musk smell

1.5 g of the ketone prepared according to Example 2b) are hydrogenated as described in Example 3.

The IR spectrum shows that a saturated ketone is present.

Odor assessment:

The odor is similar to that of the compound prepared in Example 3.

Example 5

OH

2.5 g of the ketone obtained according to Example Ibi), dissolved in 10 ml of THF, are added _{dropwise to a solution of 03 g of LiAlH 4} in 50 ml of THF. The reaction mixture is then refluxed for a further hour. It is then decomposed with 30 ml of water, filtered, and the organic phase is dried and concentrated. 2.4 g of n-hydroxy-IS-methyl-bicyclo [103.0] -pentadec.-n- [l (12)] remain as a colorless substance which melts at 90 ° C. after recrystallization from petroleum ether

Odor assessment:

musky, flowery, woody

Example 6
OH

After recrystallization from petroleum ether, the point is 74 to 76 ° C.

Odor assessment:

Sandalwood direction, very extensive, strongly adherent

Example 7

8 g of the 1-hydroxyl-tS'-hydroxy-l'-butyn-l'-ylj-cyclododecane prepared according to Example la) be with

90 ml of glacial acetic acid and 5 ml of 85% H ₃ PO * are added and the resulting mixture is heated to boiling under reflux cooling for 1 hour. Subsequent work-up as in Example Ibi) gives 7.8 g of residue, which according to IR and NMR spectra and thin-film chromium

r, matography from a mixture of 13-oxo-15-methylbicyclo (10.3.0] -pentadecen- [l (I2)] and l- [3'-acetoxy-Γ-butyn-l'-yl] -l-cyclododecene consists, which is separated by chromatography or distillation into its components w * C "uCri ΚαΓιΓί.

'"Example 8

ai) 10 ml of a 45% solution of BF ₃ in glacial acetic acid are added to 100 ml of glacial acetic acid at 20.degree. To this mixture are added 25 g of the example la)

r, 1-hydroxy-1- [3'-hydroxy-l'-butyn-1-yl] -cyclododecane obtained and the reaction mixture is heated to boiling under reflux for 1 hour. at afterwards, working up analogously to example lbi) is obtained 11 g of pure IS-Oxo-IS-methyl-bicycloflOJ.Oj-pen-

m tadecen- [1 (12) l

a?) Do you work as described under 8ai), but instead of LöO + 10 m! Glacial acetic acid to dissolve BF ₃ 100 + 10 ml dioxane, one comes to approximately the same result.

Example 9

To a mixture of 100 ml of glacial acetic acid and 3 g of p-toluenesulfonic acid, 10 g of the according to Example la) are added in portions ^{at 6O 0 C within 30 minutes.}

4 (i obtained 1-hydroxy-l- [3'-hydroxy-l'-butyn-l'-yl] -cyclododecane added, the reaction mixture then 1 hour under reflux to boiling heated and then worked up in the manner described in Example Ibi). 9.7 g are obtained

ι-, a crude product that after thin-layer chromatography Analysis corresponds approximately to the dark oil obtained as a crude product in example lbi).

Example 10
-, oa) production of the starting material

60

13 g of the ketone obtained according to Example 2b) are _{reacted with LiAlH 4} as described in Example 7. 13 g of IS-hydroxy-IS-ethyl-bicyclo [103.0] pentadecene [l (12)] are obtained. The melting

OH

OH

C = C

256 g are added to a mixture of 245 g of KOH in 2000 ml of THF in the course of 60 minutes at 0 ° C Cyclododecanone and 140 g of l-butyn-3-ol in 700 ml of THF are then added Stirred for hours at 0 ° C. and 40 hours at room temperature, 500 ml of water were added dropwise and the aqueous solution Phase separated from the organic phase, the THF is distilled off under reduced pressure The residue was extracted several times with petroleum ether. 199 g of 1-hydroxy-l- {3'-hydroxy-l'-butyn-1-yrj-cyclododecane remain. Become from the petroleum ether solution

100 g of cyclododecanone recovered. The yield is 56% of theory, based on the cyclododecanone used, or 91% of theory, based on converted cyclododecanone.

b) Rearrangement of the acetylene glycol to the bicyclopentadecene

42 g of the l-hydroxy-l- [3'-hydroxy-i'-butyn-l'-yl] -cyclododecane obtained are within 10 minutes at 60 ° C in portions to form a mixture of 330 ml of glacial acetic acid and 14 ml of concentrated sulfuric acid are added. The reaction mixture is then 60 minutes heated to boiling under reflux cooling. The work-up takes place analogously to Example Ibi). You get 28.5 g of a dark oil. The distillation gives 27.5 g

13-Oxo-15-methyl-bicyclof 10.3.0} -pen tadecen- [1 (12)},
corresponding to a yield of 70% of theory, based on the 1-hydroxy-l- [3'-hydroxy-l'-butyne-1 '-ylj-cyclododecane used.

Claims (1)

Patent claims: 1. 15-methyl and IS-ethyl-IS-hydroxy and 13-Oxobicyclo [l 03.0] -pentadecane or -pentadecene- £ l (12)] of the general formula I 0) R ¹