CS257742B1 - Process for preparing Z-alkenes derivatives - Google Patents

Abstract

The solution relates to a method for preparing Z-alkene derivatives, which are components of the sex pheromones of a number of insect pests or are important intermediates in their production. The compounds are prepared according to the invention by a modified Wittig reaction, which provides significantly higher yields of products. The novelty is the use of methylsulfonylmethane as a catalyst for the reaction of an aldehyde with a phosphonium salt.

Description

The invention relates to a process for the preparation of Z-alkene derivatives which are constituents of sexual pheromones of a number of insect pests or are important intermediates in their production.

Sexual pheromones of butterflies (Lepidoptera) are composed predominantly of unbranched aliphatic alcohols, acetates or aldehydes of 10 to 18 carbon atoms and one or two double bonds in different positions and with geometric isomerism E or Z. It is currently well established (Jones 0. T. : Chemical Mediation of Insect Behavior in Insecticides, Hutson DH, Roberts TR, Eds., Chapter 8, Wiley New York 1985) that butterfly pheromones are generally multicomponent mixtures that in many cases contain precisely defined amounts of both the E and Z geometric isomers (Arn H. et al.: List of sex pheromones of Lepidoptera and related attractants, IOBC-WPRS, 1986). Also known are several pheromones of Diptera, which are hydrocarbons having 20 to 35 carbon atoms and 1 to 3 double bonds with geometric isomerism Z (Kydonieus AF and Beroza M .: Insect suppression with controlled rherease pheromone systems, CRC Press Boca Raton, 1982).

Hitherto known methods for the preparation of Z-alkene derivatives (Henrick CA: The synthesis of insect sex pheromones, Tetrahedron 33, 1845 (1977); Sonnet PE: Tabulation of selected methods of syntheses that are commonly employed for insect sex pheromones in Techniques in Pheromone Research, Hummel, E., Miller, TA, Eds., Springer Verlag, Berlin 1984), are mostly based on the reaction of alkylacetylenes with a halogenated derivative of the corresponding moiety using either an alkali amide or non-monosubstituted Grignard reaction catalyzed by monovalent copper salts. The obtained alkyl is then selectively hydrogenated to the desired alkene either on a Lindlar catalyst or on P2-nickel. The disadvantage of these processes and their modifications is in any case the need to protect the free hydroxyl group in the form of tetrahydropyranyl or other ethers, on the one hand guaranteeing the stability of the substances in an alkaline medium, but on the other hand prolonging the synthesis by two steps (protection). Not negligible is the need to work with relatively large quantities of liquid ammonia.

Another method of synthesis (Horiike M. et al.: Agric. Biol. Chem. 44, 257 (1980); Bestmann AJ, Vostrowsky O. in Chemie der Pflanzenschutz und Schadlingsbekamppungsmittel (R. Wegler ed.), Springer Verlag 1981) is based on a Wittig reaction of omega-halo-alpha-alkanols with triphenylphosphine in a polar solvent (usually acetonitrile) to form a crystalline phosphonium salt from which the ylide is reacted with base to react further with the corresponding aldehyde to form a mixture of Z and E alkenes. The liberation of the ylide is carried out either with lithium bases (butyllithium, lithium amide) or with dimethylsulfoxide sodium (dimxyl sodium). However, the latter procedure entails some risk, given the potentially explosive nature of the reaction of dimethylsulfoxide with sodium hydride (Muller E. in Methoden der organischen Chemie, Bd. V / 2a, Thieme Verlag, Stuttgart 1977, p. 360, note 5) and in addition, the published yields of this reaction with lower aldehydes do not exceed 35% (e.g., the yield of the corresponding phosphonium salt with butanal in the preparation of (Z) -8-dodecen-1-yl acetate does not exceed 32%).

It has now been found that the liberation of the ylide from the phosphonium salt is preferably carried out with sodium methylsulfonylmethanide, the preparation of which does not present an explosion hazard and, moreover, generally increases the yield of the reaction of the phosphonium salt with the aldehyde.

The present invention provides a process for the preparation of Z-alkene derivatives of formula (I)

R ¹ - CH = CH - R ² , (I) where r! is alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms or alkoxycarbonylalkyl of 1 to 3 carbon atoms in the alkoxy moiety and 1 to 20 carbon atoms in the alkyl moiety and is alkyl of 1 to 20 carbon atoms, alkenyl of 3 to 20 carbon atoms 20 carbon atoms, omega3 257742

-hydroxyalkyl of 2 to 20 carbon atoms, omega-R-O-alkyl of 2 to 20 carbon atoms in alkyl and wherein R is a conventional protecting group.

Wittig reaction of the aldehyde of formula II

R ¹ - CHO (II) where r! is as defined above, with a compound of formula XII

R ² - P ⁺ Ph ₃ X - (III) where

R is as defined above,

Ph is phenyl and

X is a halogen atom, characterized in that the reaction is carried out in the presence of sodium methylsulfonyl methanide in a polar organic solvent, preferably dimethylsulfoxide, tetrahydrofuran or mixtures thereof at a temperature of -60 ° C, preferably 0 to 30 ° C, after which the reaction is decomposed in a manner known per se for Wittig reactions.

Sodium methylsulfonylmethanide is prepared in situ by reaction of sodium hydride and dimethylsulfone in dimethylsulfoxide, after dilution of the formed solution of sodium methylsulfonylmethanide with anhydrous tetrahydrofuran, the corresponding alkyl triphenylphosphonium bromide is added dropwise and after cooling, preferably to about zero, the appropriate aldehyde. The reaction mixture was then stirred for 1 hour, quenched by pouring into ice water and the product isolated by extraction into ether. The optional conversion to the corresponding pheromone is carried out in a conventional manner by deprotection, reduction and / or acetylation. The final product usually contains 93 to 97% of the Z isomer and 3 to 7% of the E isomer, which in some cases is directly suitable for the preparation of active mixtures, such as for Eastern and Plum Coaters.

The invention will be illustrated in more detail by the following non-limiting examples.

Example 1

Preparation of 8-hydroxyoctyl-triphenylphosphonium bromide. '

A mixture of 41.8 g (0.2 mol) 8-bromooctan-1-ol and 55.0 g (0.21 mol) triphenylphosphine was refluxed in 500 ml abs. After evaporation of the solvent, the product was heated briefly (about 15 minutes) with an equal volume of toluene to 100-110 ° C and the toluene extract was separated. The semi-crystalline residue was recrystallized from acetone. The yield of phosphonium salt (III) is 74.2 g (79%), m.p. Mp 131-133 ° C.

Preparation of (Z) -8-dodecen-1-ol.

In a three-necked flask (1 L) equipped with a reflux condenser with liquid cap to control inert gas flow and stirrer, a mixture of 7.56 g (0.32 mol) of sodium hydride and dimethylsulfone (29.7 g, 0.32 mol) in 250 ml dry dimethyl sulfoxide at 65 ° C for 45 minutes. After cooling the reaction mixture to room temperature, the solution of sodium methylsulfonylmethane formed was diluted with 200 mL dry tetrahydrofuran and a solution of 74.2 g (0.157 mol) of 8-hydroxyoctyl-triphenylphosphonium bromide in warm dimethylsulfoxide (75 mL) was added dropwise. The reaction mixture was further stirred at room temperature for 30 min. Then the reaction mixture was cooled to 0 ° C (ice bath) and freshly distilled butanal (11.3 g, 0.157 mol) was slowly added dropwise. After the dropwise addition of butanal was added dropwise, the reaction mixture was stirred for 1 hour then poured into ice water (250 ml) and extracted with ether (3 x 150 ml). The extract was washed with water, dried over MgSO 4 and evaporated on a rotary evaporator.

The evaporation residue was extracted with petroleum ether (3 x 70 ml), the solvent was removed on a rotary evaporator and the residue was distilled in vacuo. 14.5 g (50%) of (Z) -8-dodecen-1-ol were obtained,

b.v. 90-92 ° C / 40 Pa. The purity of the product was 97% according to gas chromatography. The isomer representation was determined after acetylation and the Z to E ratio was 94 to 6. The NMR and MS spectra were consistent with the structure.

Example 2 v

Using the procedure of Example 1 but substituting 8-bromooctan-1-ol and butanal for an equivalent amount of 1-bromo-tetradecane and nonanal, (Z) -9-tricosene was prepared. Yield of modified Wittig reaction 81%. Isomer content Z / E = 97/3. Gas chromatography and IR, MS, and NMR spectra were consistent with the structure.

Example 3

Using the procedure of Example 1, but substituting 8-bromoctan-1-ol and butanal for equivalent amounts of 9-bromnonan-1-ol and (E) -2-pentenal, (Z) -9- (E) -11-tetradecadiene- l-ol. Yield of modified Wittig reaction 68%, content of (Z), (E) -isomer 93%. Gas chromatography and IR, MS, and NMR spectra were consistent with the structure.

Example 4

Using the procedure of Example 1 but substituting 8-bromooctan-1-ol and butanal for an equivalent amount of (E) -3-pentenyl bromide and 8-formyloctan-1-yl acetate, (Z) -9- (E) -12- tetradecadien-1-yl acetate. Yield of modified Wittig reaction 76%, content of (Z), (E) -isomer 95%. Gas chromatography and IR, MS, and NMR spectra were consistent with the structure.

Example 5

Using the procedure of Example 1 but substituting 8-bromooctan-1-ol and butanal for an equivalent amount of (Z) -4-nonenyl bromide and ethyl 6-formylhexanoate, ethyl (Z) -7- (Z) -11-hexadecadienoic acid ethyl ester was prepared, which, after reduction with lithium aluminum hydride (ether, 0 ° C), affords (Z) -7- (Z) -11-hexadecadien-1-ol. Yield of modified Wittig reaction 71%, content of (Z), (Z) -isomer 94.5%. Gas Chromatography retention time and β, MS and NMR spectra are in accordance with the indicated structure.

Claims (2)

object of the invention A process for the preparation of Z-alkene derivatives of the general formula I R ¹ -CH = CH-R ² (I) wherein is alkyl of 1 to 20 carbon atoms, alkenyl of 2 to 20 carbon atoms, or alkoxycarbonylalkyl of 1 to 3 carbon atoms in the alkoxy moiety and 1 to 20 carbon atoms in the alkyl moiety, and is alkyl of 1 to 20 carbon atoms, alkenyl of 3 to 20 carbon atoms, omega-hydroxyalkyl of 2 to 20 carbon atoms, omega-RO-alkyl of 2 to 20 carbon atoms in alkyl, and wherein R is a conventional protecting group, Wittig reaction of the aldehyde of formula II R ¹ - CHO (II) wherein R ³ is as defined above, with a compound of formula III R ² - P ⁺ Ph ₃ x (III) where R is as defined above, Ph is phenyl and X is a halogen atom, characterized in that the reaction is carried out in the presence of sodium methylsulphonyl methanide in a polar organic solvent, for example dimethylsulphoxide, tetrahydrofuran or mixtures thereof at -60 ° C to 50 ° C, after which the reaction is decomposed in a manner known per se in Wittig's reactions. 2. The process according to claim 1, wherein the reaction is carried out at a temperature of 0 to 30 ° C