CH521296A - Terpene derivs prepn intermediates for - sinensal cpds - Google Patents

Abstract

Terpene derivs; useful as intermediates in prepn. of aromatising cpds. such as beta-sinensal cpds., have the formula (I): (wherein R is CHO, COOH or CH2OH; only one of the dotted lines represents a bond). Prefd. cpd. are 4-methylene-5-hexen-1-ol; 4-methylene-5-hexen-1-al; 4-methyl-3,5-hexadien-1-ol. The cpds. are prepd. by ozonising cpds. of formula (II) e.g. myrcene, and decomposing the ozonised product.

Description

  

  
 



  Process for the preparation of a terpene derivative The invention relates to a process for the preparation of a compound of the formula
EMI1.1
 which is characterized in that myrcene is ozonated, the ozonation product obtained by treatment with a mild reducing agent to form the aldehyde of the formula
EMI1.2
 where Ph is a phenyl group and the symbols R1 are lower alkyl groups, which also reduce to a lower alkyl group, this with a phosphorane of the formula
EMI1.3
 len group (e.g.

   Ethylene) can be linked to a triene acetal of the formula
EMI1.4
 converts the resulting triene acetal, optionally after isolation of the cis or trans isomer, to the trienaldehyde of the formula
EMI1.5
 hydrolyzed and this with a phosphorane of the formula
EMI2.1
 to the tetraenaldehyde of the formula I.
The following scheme illustrates the method according to the invention:
EMI2.2
    Surprisingly, in the first stage of the process according to the invention, the ozonization of the triene II proceeds with high selectivity, in that the ozonide formation takes place practically exclusively on the isolated double bond, i.e. the conjugated double bonds practically do not react with the ozone.



   The ozonization can be carried out by methods known per se by bringing ozone-containing gas into contact with the triene to be ozonized, expediently by introducing the gas into a preferably dilute solution of the triene. Particularly suitable solvents are those which are inert to ozone or at least have greater stability than the substance to be ozonated; e.g. Alkanes such as hexane, petroleum ether, cyclohexane; Benzene and its derivatives; halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride, methyl chloride, ethyl chloride, ethyl bromide; Esters, such as formic acid or acetic acid ester (ethyl acetate); Ketones such as acetone or methyl ethyl ketone; Ethers, such as dimethyl ether, diethyl ether, tetrahydrofuran; Acid anhydrides such as acetic anhydride; Acid amides such as formamide, dimethylformamide; Nitromethane etc.

  Solvents that react with the ozonide formed primarily, such as e.g. Carboxylic acids, for example formic acid, acetic acid, propionic acid; Alcohols such as methanol, ethanol, propanol; Water mixed with acetone. Solvents that are able to keep the ozonation products in solution are best suited. Furthermore, low-boiling solvents are to be preferred, since these are generally easier to separate off from the reaction products. For the
Ozonization of myrcene particularly suitable solvents are e.g .: methyl chloride, chloroform, carbon tetrachloride, benzene, acetone, ethyl acetate, methanol.



   The concentration of the solution to be ozonated can vary within wide limits. Dilute solutions generally give better yields. For practical reasons, 5-20% solutions will usually be used.



   It is advisable not to let more than about 1 molar equivalent of ozone act on the triene II, the myrcene, in order to avoid oxidation of the reaction product. Typically an oxygen stream with an ozone content of about 2-10% is used. However, more dilute and more concentrated ozone mixtures are also possible. It is also possible to use oxygen-free ozone (as a gas or as a solution).



   It is advisable to carry out the ozonization at temperatures below room temperature, expediently at temperatures below 0 ° C. Particularly good yields are obtained at temperatures in the range from about -50 to 900 ° C.



   The cleavage of the ozonation product obtained primarily to the compound of formula III by treatment with a mild reducing agent can e.g. by treatment with an iodide (e.g. sodium or potassium iodide), sulfite, bisulfite (e.g. sodium bisulfite), with formaldehyde, sulfur dioxide, pyridine, hydrazine hydrate, with a sulfide (e.g. dimethyl sulfide), with hydroquinone, zinc or magnesium in acidic solution, with a Silver salt, with Raney nickel etc. can be made.



   The aldehyde obtained in this way is converted into a triene acetal of the formula V in a Wittig reaction with a phosphorane of the formula IV. The formula V comprises the trans isomer Va and the cis isomer Vb.



   The preparation of the phosphorane IV (as well as the phosphoranes still mentioned below) and the reaction with the carbonyl component III can take place according to the methods of the Wittig reaction known per se (cf.



   Angewandte Chemie 71 [1959], 260). It is practical to proceed in such a way that the carbonyl component is added to a freshly prepared solution or suspension of the phosphorane.



  The triene acetal V
EMI3.1
 is then, optionally after separation of the mixture of the cis-trans isomers (e.g. by means of preparative gas chromatography), to the corresponding trienaldehyde of the formula
EMI3.2
 (comprising the trans isomer VIa and the cis isomer VIb) hydrolyzed. The hydrolysis of the acetal V to the aldehyde VI can be accomplished by the usual methods of acetal saponification.



   Finally, the trienaldehyde VI, again according to Wittig, is converted into the tetraenaldehyde of the formula I by reaction with a phosphorane VII
EMI3.3
 implemented. The formula I comprises the trans isomer Ia (natural ss-sinensal) and the cis isomer Ib.



   The compounds obtainable according to the invention via the new aldehyde III are substances with an orange aroma, in particular the ss-sinensal (trans-ss-sinensal: 2,6-dimethyl10-methylene-2t, 6t, 11-dodecatrienal) occurring in orange oil (Citrus sinensis) , as well as the isomer of the same (cis-ss-Sinensal), due to which the compound for aromatization, e.g. of drinks, can be used.



   In the following example, the temperatures are given in degrees Celsius.



   example
In a solution, cooled to -80 ", of 10 g (73.5 mmol) of myrcene in 50 ml of methanol, 73.5 mmol of ozone are passed in about 3 hours. The still cold solution is then briefly flushed with nitrogen and treated with 6.8 g (110 mmol) Dimethyl sulfide is added, the cooling bath is removed and the reaction mixture is allowed to warm up.



  After about 1.5 hours, the mixture is concentrated to about 1/3 volume on a rotary evaporator (maximum bath temperature is 30). The residue is taken up in ether and the solution is shaken twice with water. The solution, dried over sodium sulfate, is freed from ether. The residue is distilled in a water jet vacuum. 6 g (74% of theory) of 4-methylene-5-hexen-1-al with a boiling point of 50-55 "/ 11 mm are obtained.



  IR bands at 2700, 1750, 1600, 905 cm- '.



   1.51 g (3.0 mmol) of finely powdered (4-ethylenedioxybutyl) triphenylphosphonium iodide are slurried in 10 ml of tetrahydrofuran and a solution of 4.5 mmol of butyllithium in hexane is added dropwise. While the solution turns red, the phosphonium iodide goes into solution as phosphorane [(4-ethylenedioxy-butylidene) triphenyl phosphorane]. After about 10 minutes, 0.25 ml (4.5 mmol) of methyl iodide is added to the phosphorane solution. The solution becomes lighter and some of the phosphonium salt [(4-ethylenedioxy-1-methylbutyl) triphenylphosphonium iodide] formed precipitates out as an oil. After 10 minutes, 3.0 mmol of butyllithium in hexane is added dropwise.



  The solution turns dark red again.



   After 10 minutes, 330 mg (3.0 mmol) of 4-methylene-5-hexenal (III), dissolved in 1 ml of tetrahydrofuran, are added to this solution containing phosphorane IV (Rt + R1 = ethylene). The solution then partially discolors again. After 30 minutes, 100 mg of sublimed potassium tert-butoxide are added. The mixture is stirred for a further 1.5 hours, then taken up in pentane and the insoluble part which has precipitated out is decanted off. The pentane extract is then washed neutral with water and dried over sodium sulfate. After removing the solvent, the residue is distilled. 421 mg (63%) of a cis-trans isomer mixture of the triene acetal V (R1 + R1 = ethylene) are thus obtained in the form of an oil with a boiling point of 1600/0, lmm; n2l) = 1.4930.

  IR bands at 1600m, 1145s, 900scml.



   The ratio of the trans isomer Va (4-methyl-8-methylene-4t, 9-decadienal-ethylene acetal) to the cis-isomer Vb (4-methyl-8-methylene-4c, 9-decadienal-ethylene acetal) is about 1: 1 The isomer mixture can be separated by gas chromatography.



   The phosphonium iodide mentioned at the beginning, (4-ethylenedioxy-butyl) triphenylphosphonium iodide, melting point 172-177 ", can be obtained as follows: 4-chlorobutyric acid chloride is reduced to 4-chlorobutanal according to Rosenmund, this aldehyde is acetalized with ethylene glycol, the product obtained with sodium iodide converted into the corresponding iodide acetal (ethylene acetal of 4-iodobutanal) and the latter reacted with triphenylphosphine.



   146 mg (0.65 mmol) of the triene-ethylene acetal V obtained (as a mixture of cis-trans isomers) are dissolved in 3.7 mol of dioxane and 1.2 mol of 0.1N sulfuric acid. The solution is refluxed for 2 hours, then taken up in ether, washed neutral with sodium bicarbonate solution and dried over sodium sulfate. After removing the solvent, the oily residue is distilled. This gives 97 mg (83%) of a cis-trans isomer mixture of trienaldehyde VI, 4-methyl-8-methylene-4,9-decadienal, with a boiling point of 1000/0.1 mm.



   In an analogous manner, the pure cis and trans isomers Vb and Va (obtained from the isomer mixture V by means of preparative gas chromatography) are converted into the cis isomer VIb (4-methyl-8-methylene-4c, 9-decadienal) and trans -Isomers VIa (4-methyl-8-methylene-4t, 9-decadienal) saponified. n2r0, value and IR spectrum of the two isomers obtained are identical: n2r = 1.4909; IR bands at 2700m, 1725s 1600m, 900cm¯1.



     175 mg (0.98 mmol) of the trans-trienaldehyde VIa (4-methyl-8-methylene-4t, 9-decadienal) obtained and 318 mg (1.0 mmol) of phosphorane VII, (α-formylethylidene) triphenylphosphorane , are dissolved in 5ml benzene. The solution is refluxed for 40 hours, the benzene is then filtered off with suction, the residue is treated with pentane, the precipitated phosphine oxide is filtered off and the pentane is evaporated again. The remaining oil is distilled. 161 mg (75%) of pure trans-ss Sinensal Ia (2,6-dimethyl-10-methylene-2t, 6t, 11 -dodecatrienal) with an approximate boiling point of 1000 / 0.1 mm are obtained in this way; n2D0 = 1.0577; IR bands at 1700s, 1600w, 900 scm-l.

 

   In a corresponding manner, by reacting 158 mg (0.89 mmol) of the cis-trienaldehyde VIb with 290 mg (0.9 mmol) of the phosphorane VII, 157 mg (81%) of cis-ss-sinensal Ib with an approximate boiling point of 100 "/ 0.1 mm are obtained ; n2r0 = 1.5078; IR bands at 1700s, 1600w, 900cm¯1.



   Phosphorane VII (melting point 220-222) can be obtained as follows: Ethyl iodide is reacted with triphenylphosphine in benzene to give ethyl triphenylphosphonium iodide and this is reacted with butyllithium and methyl formate.

 

Claims (1)

PATENT CLAIM Process for the preparation of a compound of the formula EMI4.1 characterized in that myrcene is ozonated, the ozonation product obtained by treatment with a mild reducing agent to the aldehyde of the formula EMI4.2 reduced this with a phosphorane of the formula EMI5.1 where Ph is a phenyl group and the symbols R1 are lower alkyl groups, which can also be linked to form a lower alkylene group, to a triene acetal of the formula EMI5.2 converts the triene acetal obtained to the trienaldehyde of the formula EMI5.3 hydrolyzed and this with a phosphorane of the formula EMI5.4 to the tetraenaldehyde of the formula I. SUBCLAIMS 1. The method according to claim, characterized in that the trans isomer is isolated from the mixture of the cis-trans isomeric triene acetals of the formula V and this is converted into trans-ssSinensal. 2. The method according to claim, characterized in that the cis-isomer is isolated from the mixture of the cis-trans-isomeric triene acetals of the formula V and this is converted into cis-ss-sinensal.