DE2630428C3 - 15-methyl- and 15-ethyl-13-oxo- or -13-hydroxy-bicyclo [10.3.0] pentadecane or pentadecene [1 (12)], process for their production and use as odorants - Google Patents

Description

X = O or

- H
-OH

means.

2. Process for the preparation of 13-hydroxy or U-Oxo-bicyclotlOJ.Oj-pentadecanes or -pentadecenes - [! (12)] according to Claim I, characterized in that acetylene glycols are used general formula II

= C-CH

in which R has the meaning given above ^1, in the presence of an acidic catalyst system with an acid strength equal to or greater than of HCOOH or Lewis acids at temperatures of 50 ⁰ C to 200 ⁰ C, preferably 50 ⁰ C to 150 ° C , heated and in the event that A and B stand for H, the obtained IS-alkyl-n-oxo-bicyclo [10.3.0] -pentadecacen- [l (12)] in the presence of Pd-, Pt- or Ni -Catalysts hydrogenated or for the

Case that X

- H
i-OH

is the compounds of the formula of certain 1-hydroxy-1 - [3'-hydroxy-alkinyI] -cyclododecanes.

It is well known that macrocyclic musk fragrances are like muscone, cyclopentadecanone, cyclohexadecanone etc. all due to their olfactory properties Superior to other known musk fragrances, such as tetralin or nitromusco 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 connections is therefore very large.

It was therefore the object of the invention to provide a technically simple and inexpensive process for producing new ones to develop good musk fragrances.

From the German Auslegeschrift 16 68 054 the production of 13-Oxo-14-methyI-bicyclo [10J.0] -pentadecen- [l (I2)] known as an intermediate in the manufacture of muscone. The one in the above-mentioned interpretative document However, the production processes described are more difficult to access because of the need for numerous reaction stages or because of their use and therefore expensive reactants or reagents technically not very attractive.

It has now surprisingly been found that the new IS-oxo-bicycloflOJ.OJ-pentadecanes or -pentadecene- [l (12)] more generally Formula I.

I with X = O with LiAIH ^ NaBH4, after Meewein-Ponndorf reduced with aluminum isopropylate or with nickel and hydrogen.

3. Use of 13-oxo- or 13-hydroxy-bicyclo [l0.3.0] pentadecanes or -pentadecene- [l (l2)] according to claim I as musk fragrances.

in the

R 'for-CHjoder-arises,

A and B either both stand for H or A and B

to put together 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

r> musk fragrances on the market is extraordinarily similar. The compounds of formula I with

I - O H

show musky and sandalwood fragrances

th.

The new 15-methyl- or IS-ethyl-13-oxo n-hydroxy-bicyclofJO.i.OJ-pentadecane or -penladecene- [l (l2)] of the general formula 1 can be prepared in a simple manner by acetylene glycols of the general formula II

OH

= C-CH

The invention relates to 15-methyl- or 15-ethyl-U-oxo- or 13-hydroxy-bicyclo- [l0.3.0] -pentadecanebzw. -pentadecene- [l (l2)], which have excellent properties as musk fragrances, and processes for their preparation by acid-catalyzed rearrangement in the R ¹ -CHi or -CjH-, means in the presence of an acidic Kalalysatorsystcms with an acid strength equal to or is greater than that of HCOOH or of Lewis acids at temperatures of 50 to 200 "C,

preferably 50 to 150 ° C, heated and in the event that A and B stand for H, the obtained 15-alkyl-13-oxo-bieyclo [103.0] -pentadeeen- [l (12)] hydrogenated in the presence of Pd, Pt or Ni catalysts or in the event

TT

is, the compounds of the formula with

X = O with LiAlHi, NaBhU, according to Meerwein-Ponndorf reduced with aluminum isopropylate or with nickel and hydrogen

Since the acetylene glycols of the general formula II are easy and known (see for example HeIv. Chim. Acta 56 [1973J p. 1503 and Houben - Weyl, "Methods of Organic Chemistry", Volume 4/2 [1955], p.413f) by reacting cyclododecanone with the Acetylene alcohols of the formula III which are very readily available on an industrial scale

OH

R ¹

(III)

in the presence of bases such as KOH, NaOCHi, NaH, NaNH ₂ , CH ₃ MgCl, KO-tert-aH ,, or basic ion exchangers at temperatures from -50 to + 150 ⁰ C, preferably at about 0 ° to 50 "C, can be produced, there is thus a technically simple and very advantageous synthetic route from the technically easily accessible cyclododecanone to the new 15-AUyl-13-oxo-bicyclo [l0.3.0] -pentadecene- [l (12)], which are interesting as musk fragrances Per.tadecenes can be converted into the corresponding pentadecanes in a manner known per se dui .ti hydrogenation in the presence of Pd, Pt or Ni catalysts, which are also of interest as fragrances with a musky note.

- H

The compounds of formula I with X =

-OH

obtained by reduction with LiAlH ₄ , NaBH ₄ , according to Meerwein-Ponndorf with aluminum isopropylate or with Ni and H2. The 13-hydroxy-bicyclo [10J.0] pentadecane or pentadecene [1 (12)] obtained have the general formula IV

OH

(IV)

in the

Rt is - CH j or -C ₂ H ₅ and
A and B either both stand for H or A and B together represent an additional bond between the C-breaths that carry them,
obtain.

Can be prepared by a per se known esterification with lower carboxylic acids, their acid chlorides or their anhydrides are prepared from the corresponding Carbonsäureester the D-hydroxy-bicycloflOJ.Ojpentadecanen or -pentadecenen- [l (l2)] of the general formula IV, r is obtained from B. 13-Hydroxoxy-15-äÜiyl-bicyclo [10,3, o; | -deeen- [l (12)] and acetyl chloride the corresponding 13-acetoxy derivative,

Furthermore, the new 13-oxo-15-methyl-bicyclo [103.0] pentadecen- [l (12)] a surprisingly beneficial way to make the coveted muscone. The manufacture of d, I-Muscon from the said » Compound can be through ketalization, ozonolysis, Wolff-Kishner reduction and subsequent de-ketalization take place.

For the preparation of the new 13-Oxo-bicycIo [10J.O] -pentadecane or -pentadecene- [l (12)] of the general formula I are used as starting materials Acetylene glycols l-hydroxy-l- [3'-hydroxy-l'-butyn-ryl] -cyclododecane and l-hydroxy-l- [3'-hydroxy-l'-pentyne-1 '-ylj -cyclododeean.

Suitable catalysts for the rearrangement of the acetylene glycols of the general formula 11 are generally all acids or acidic systems which have an acid strength that is equal to or greater than that of formic acid, that is to say, a pKa value equal to or less than a! S about 3.77 and which do not otherwise attack the starting 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, H3PO4 diluted with acetic acid, HCl, especially HCl in the form of HCl-saturated ether, p-toluenesulfonic acid, phosphorus pentoxide in benzene, KHSO ₄ , MgSO ₄ and NaHSO ₄ , in particular HCOOH, H ₂ SO ₄ , HCl and HjPO ₄ as such, in mixtures with one another or diluted with water or organic solvents such as Ci- to Q-alcohols, hydrocarbons or ethers such as dioxane, but also Lewis acids such as BFj, 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 tO mol, based on 1 mol Acetylene glycol. The use of multiple molar amounts, i. H. so the simultaneous use the catalyst as a solvent is particularly recommended when using aqueous formic acid.

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

For more details on this so-called Rupe = or Meyer ^ Schuster * reference rearrangement see Swaminathan, S. et al., Chem. Reviews 71 (1971). 5, pages 429 to 434 and J. Am. Chem. Soc. 75 (1953). 4740.

The work-up of the reaction mixture is successful! in the usual way, e.g. by pouring into ice cream wafers or Ice, extraction with an inert solvent which is immiscible or only slightly miscible with water and then

Send distillation. The final purification of the 'roducts obtained is also by chromatography or To achieve crystallization.

The hydrogenation of the 13-oxo-bicy-: Io [) 0J3,0] pentadecene- [1 (12)] obtained can be carried out in the presence of Mi, Pd or Pt catalysts with or without a support material, at normal pressure or elevated pressure temperatures from 0 ° to 200 ° C, preferably carried out at 50 ° to 100 ⁰ C. C, SiO ₂ , AhCj or CaCO ₃ , in particular C ivt, come into consideration as catalyst supports. The most advantageous pressure range is around 50 to 100 bar.

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. Schüler in Houben-Weyl, Vol. IV / 2, pages 248 to 303 (1955) and K. Wimmer in Houben-Weyl, Vol. IV / 2, pages 143 to 152, 163 to 192 (1955).

example 1
a) Production of the starting material

OH OH

th acetylene glycol was added and the reaction mixture was stirred at 60 ° C. for 1 hour. The mixture is then poured onto ice and extracted with petroleum. 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 _{pale yellow liquid with a boiling point of K po} .i5 = 123 ° C, which slowly crystallizes. Fixed point = 54 to 56 ° C., yield = 57% of theory, based on the 1-hydroxy-1 - [3'-hydroxy-l'-butyn-1'-ylj-cyclododecane used. IR, NMR, Cu-NMR spectra and analysis confirm the structure.

Odor assessment:

fine musky odor

bj) If you work as described under 1 bi), however, instead of the mixture of glacial acetic acid and sulfuric acid, 150 ml of 80% formic acid and Temperatures of 80 "C so you get the same result.

Example 2
a) Production of the starting material

A Grignard solution is prepared from 17 g of Mg turnings in 200 ml of tetrahydrofuran (THF) with CH _{3 Cl.} 3-, With cooling, 24.5 g of 1-butyn-3-ol are added dropwise. After the vigorous evolution of gas has ceased, 57.6 g of cyclododecanone in 150 ml of THF are then added dropwise at 0 ° C. and the reaction mixture is stirred overnight at room temperature. _w

It is then decomposed with 100 ml of water, the organic phase is separated off, dried and concentrated. 65 g of a slowly crystallizing oil remain which, according to thin-layer chromatographic investigations, consists of cyclododecanone and a new 4-product. 25 g of cyclododecanone are removed by washing with petroleum ether and recovered again. 34.5 g of a colorless substance with a fixed point of 143 ° C. remain. The spectroscopic data and the analysis confirm the structure of the -, _n obtained 1-hydroxy-1 - [3'-hydroxy-1 '-butin · 1' -yl] cyclododecane. Yield 46% of theory, based on the cyclododecanone used and 74% of theory, based on converted cyclododecanone.

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

OH

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 1-pentyn-3-ol in 50 ml of ether are added dropwise to this solution. The reaction mixture is then stirred for 12 hours at room temperature, washed with water, the organic phase dried and concentrated. 87.7 g of a slowly crystallizing oil remain behind. To Washing out of 23 g of unreacted cyclododecanone with petroleum ether leaves 43.6 g of l-hydroxy-l- [3'-hydroxy-l'-pentyne-l '-ylj-cyclododecane as a colorless powder with a fixed point of 86 to 88 ° C. The yield is 51% of theory, based on the cyclododecanone used, or 89%, based on the cyclododecanone converted.

To a mixture of 330 ml of glacial acetic acid and 14 ml of conc. H2SO4 grazing within IO minutes at 50 ^C to 6O ⁰ C in portions 21.2 g of g in accordance with la) hcrgestcll-20 of Figure 2a) Acstylenglykols produced are rearranged in the manner described in Example Ib) manner.

18.2 g of crude product are obtained. From this, 6.7 g of pure IS-Oxo-IS-ethyl-bicyclo [10.3.0] -pentadeeem [1 (12)] are obtained by chromatography gained from benchmark 58 to 60 "C.

Odor assessment:

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

5.6 g of the I3-oxo-15-methyl-bicyclo- [IC.3.0] -pentadecen- [l (12)] obtained according to Example Ib,) 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-1 S-methyl-bicyclofJOJ.Oj-pentadecane remains as a colorless oil. which is distilled on a short-path still, π = 1.4948. The IR spectrum shows. that the double bond is quantitatively hydrogenated.

Odor assessment:

fine musky odor

Example 4

1.5 g of the according to the example! 2b) produced ketones are hydrogenated as described in Example 3.

The IR spectrum shows that a saturated ketone is available.

Odor assessment:

Odor similar to that of the compound prepared in Example 3.

Example 5
OH

2.5 g of the ketone obtained according to Example Ib). dissolved ir, 10 ml of THF are added to a solution of 0.3 g LiAIH. 50 ml of THF were added dropwise. Then the The reaction mixture was heated to boiling for a further 1 hour under reflux. Then it is decomposed with 30 ml of water, filtered, the organic phase dried and concentrated. 2.4 g of 13-hydroxy-l 5-methyl-bicyclo [10.3.0] -pentadecen- [1 (! 2)] remain. as a colorless substance, which according to Ijmknstalhsation from petroleum ether at 90 "C melts.

Genjchsassung:

musky, flowery, woody

Example! 6th
OH

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

Court assessment:

Sandalwood direction, very extensive, strongly adherent

Example 7

8 g of the 1-hydroxyl- [3'-hydroxy-l'-butyn-i'-yij-cvclododecans prepared according to Example la) 90 ml of glacial acetic acid and 5 ml of 85% HjPO * are added and that mixture obtained for 1 hour under reflux cooling / heated to boiling. With subsequent work-up analogously to Example Ibi), 7.8 g of residue are obtained according to IR and NMR spectra and thin-layer chromatography from a mixture of 13-üxo-15-methylbicydo [10.3.0] -pentadecen- [l (l2)] and l- [3'-acetoxy-l'-butyn-l'yl] -l-cyclododecene, which is chromatographically or separated into its components by distillation

ijg of the ketone obtained according to Example 2b) are vk -! <* in Bonnie! 7 bev.hrieher: implemented with IjAIH «. ! .3 g: J r · ■ .Crr, i ■.] ■ '> arhyl-bicy c! O {! 0 KjJ-pentadecen-f H'2) j obtained. Dc enamel

Example 8

a _:) 10 ml of a 45% solution of BFi in glacial acetic acid are added to 100 ml of glacial acetic acid at 2OC ". 25 g of the I -hydroxy-1 - [3'hydroxy-1 'obtained according to Example la) are added to this mixture. -butyn-1'-yl] -cyclododecane and the reaction mixture is heated to boiling for 1 hour under reflux cooling. Subsequent work-up as in Example Ib,) gives Il g of pure 13-oxo-l 5-methyl-bicyclo [10.3.0] -pentadei; en- [l (12) J.

a.} If you work as described under 8a,), if, however, instead of 100 + 10 ml of glacial acetic acid to dissolve BF), 100 + 10 ml of dioxane is used approximately the same result.

Example 9

To a mixture of 100 ml of glacial acetic acid and 3 g of p-toluenesulphonic acid, 10 g of the 1-hydroxy-1 - [3'hydroxy.I'-butyn-1 -yl obtained according to Example la) are added in portions at 60 "C. over a period of 30 minutes ] -cyclododecans added, the reaction mixture is subsequently Bend I hour under reflux to boiling Ernil ti Utlu ailM-nilcucuvj aui uitl 11Ί DciSpic! worked v,} manner described above. this gives 9.7 g of a crude which NaCN thin layer chromatographic analysis as in example Ibt ) corresponds to dark oil obtained as a Ron product.

Example 10
a) Production of the starting material

OH OH

To a mixture of 245 g KOH in 2000 ml of THF over 60 minutes at 0 C ⁼ 256 g and 140 Cydododecanon lButin-3-ol g added in 700 ml THF. The reaction mixture is then stirred for 8 hours at 0 "C. and at room temperature for 40 hours, 500 ml of water are added dropwise and the aqueous phase is separated off. The THI" is distilled off from the organic phase under reduced pressure, the residue is extracted several times with petroleum ether g 1 -hydroxy-1 - {3-hydroxy-Γ-bulin-1 'ylj-cyclododecane. Become from the petroleum ether solution

9 10

! 0Og of cyclododecanone recovered. The yield 42 g of the i-hydroxy-1- [3'-hydroxy-l'-bu-

is 56% of theory, based on the tin-l'-yl] -cyclododecane used, within 10 Cyclododecanone or 91% of theory, based on minutes at 60 ° C., in portions to form a mixture of converted cyclododecanone. 330 ml of glacial acetic acid and 14 ml of concentrated sulfuric acid

b) Rearrangement of the acetylene glycol to the bicyclo-. given. The reaction mixture is then 60 minutes Pentadecene heated to boiling under reflux. the

Working up is carried out analogously to Example Ib,) · One receives 28.5 g of a dark oil. The distillation gives 27.5 g

13-Oxo-1 S-methyl-bicyclofJOJ.Oj-pentadecen-fU 1 2) \ '" corresponding to a yield of 70% of theory, based on the 1-hydroxy-1- [3'-hydroxy-Γ-butyne-Γ used yl] cyclododecane.

Claims (1)

Patent claims: 1. I5-methyl- and 15-ethyl-13-hydroxy- and 13-OxObJCyCIo [10.3.0] -pentadecane or -pentadecene- [l (l 2)] of the general formula I. in the R ^{1 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