CS207178B1 - Method of preparation of the alkins derivates - Google Patents

Description

(54) A process for preparing alkyne derivatives

The invention relates to a process for the preparation of unbranched aliphatic derivatives of alkynes which are valuable intermediates for the production of butterflies or their analogs which influence insect behavior.

Pheromones are compounds secreted by individuals of a certain species to influence the behavior of other individuals of the same species. In the last 10 years, sexual pheromones have been identified and synthetically prepared in dozens of insect species. The most violent development of research in this respect is in butterflies, both because of the female sex pheromones of relatively uniform structures and, secondly, because of the greatest chance of rapid use in butterflies under managed and integrated plant protection programs. (Pheromones, edited by M.C. Birch, Elsevier, Amsterdam 1974; Chemical Ecology: Odor Communication in Animals, edited by F.J. Ritter, Elsevier, Amsterdam 1979).

Synthetically prepared sex pheromones can be used: a) to provide the population density and flight time of the pest, allowing spraying timing and thus reducing the amount of insecticides used, b) to attract butterflies to a place where they can be killed or sterilized, c) to fight directly pests by spraying the habitat with a pheromone and the omnipresent scent of a female will prevent males from finding females. They then lay unborn eggs and the population density of the pest decreases.

Butterflies' non-monocomponent sex pheromones are predominantly non-branched aliphatic alcohols or acetates having 12 to 18 carbon atoms with 1 or 2 double bonds in different positions and geometric isomerism E or Z. A large number of butterflies have pheromones as the major component (E ) or (Z) -9-dodecen-1-yl acetate and (E) - or (Z) -111-tetradecen-1-yl acetate.

For compounds of this type in the literature (CA Henrick: The synthesis of insect sex pheromones, Tetrahedron 33, 1845 (1977); R. Rossi: Insect pheromones I, Synthesis of achiral comiponents of insect pheromones, Synthesis 817 (1977)) modification of the processes predominantly starting from the diols corresponding to the saturated part of the molecule and elongation is carried out with the appropriate acetylene. For example, several modifications of the synthesis of (E) -9-dodecenyl acetate starting from 1,8-octanediol are described. However, this synthetic process is disadvantageous for the production of larger quantities, as 1,8-octanediol is relatively expensive and, in addition, other expensive chemicals such as dihydropyran and lithium amide are used in the process. The need for more complex separation techniques for isolation and purification is also negligible

307178 synthesis of acetylenes, used for the production of butterfly pheromones, based on relatively cheap raw materials.

The present invention provides a process for the preparation of an alkyne derivative of the formula I, R ¹ - CC - (CH ₂ ) _m --O - R ² (I), wherein R ¹ is hydrogen or C 1 -C 5 alkyl,

R ² is hydrogen, C 1 -C 5 alkanoyl or CH 2 OCH 3 and m is an integer from 6 to 16, characterized in that a compound of formula II is reacted

R 1 -C 5 C- (CH ₂ ) n -X (II), wherein X is halogen or C 6 -C 12 arylsulfonyl n is an integer from 3 to 8 and R ¹ is as defined above with a compound of formula III

XMg - (CH ₂ ) _p - O - CH ₂ - O - CH ₃ (III), wherein X is a halogen atom and _p is an integer from 3 to 8, in the presence of a catalytic amount of CuCl in an organic solvent such as ethereal solvents, preferably in tetrahydrofuran, at a temperature of from 0 to 30 ° C, preferably at room temperature, whereupon optionally the compound of formula I wherein R ² is CH ₂ OCH ₃ is acid hydrolyzed to form a compound of formula I wherein R ² is hydrogen and this is optionally acylated to form a compound of formula I wherein R ² is C 1 -C 5 alkanoyl.

The starting compounds of formula II are known compounds and are prepared, for example, by reaction of the corresponding 1-bromo-n-chloroalkane with sodium alkyl acetylide.

The starting compounds of formula III are prepared by reacting ω-haloalkanols with chloromethyl methyl ether in the presence of N, N-dimethylaniline. The product obtained, which is sufficiently pure for the preparation of organometallic reagents, is converted in a known manner to the Grignard reagent of formula III by reaction with magnesium with initiation of iodine and methyl iodide.

The reaction of the compounds of formula II and III is carried out using a catalytic amount of CuCl on standing at room temperature until the starting compound of formula II disappears in the reaction mixture, as checked by gas chromatography. The reaction generally takes 7 days. Reducing the reaction time by using a higher temperature is disadvantageous as it leads to the formation of by-products. The reaction mixture is quenched with ammonium sulfate solution and the dried residue yields a compound of formula I wherein R ² is CH ₂ OCH ₃ . This compound can be used either for the preparation of acetylenic alcohols or their acetates by hydrolysis by boiling with hydrochloric acid in methanol and optionally subsequent acylation, or can be used directly to reduce the triple bond to E or Z olefins and then by acidic cleavage protecting methoxymethyl groups, optionally subsequent acylations, to give the desired pheromones or analogs thereof.

The present invention is illustrated in more detail by the following non-limiting examples.

Example 1

9-Dodecim-1-ol

a) 1-Chloro-5-octine. To 600 ml of liquid ammonia is added 500 mg of ferric nitrate hexahydrate followed by sodium (28.8 q;

1.25 mol). After changing the color of the solution from initially deep blue to light gray, ethylacetylene (68 g; 1.25 mol) was added to the sodium amide solution thus prepared. 1-Bromo-4-chloro-butane (197 g; 1.15 mol) was added dropwise with stirring to the resulting sodium ethylacetylide suspension and the reaction mixture was stirred for 1 hour. The reaction mixture is quenched by addition of 1 liter of water, the precipitated product is separated and dried after breaking the emulsion by filtration through diatomaceous earth. 1-Chloro-5-octine is purified by distillation at 66 to 69 ° C / 1 kPa. Yield 95%.

b) 1-O-Methoxymethyl-4-chlorobutanol. To a solution of 162.5 g (1.5 mol) of 4-chloro-1-butanol in benzene (400 ml) was added N, N-dimethylaniline (193 g; 1.6 mol) and added dropwise while cooling to 30 ° C. chloromethyl methyl ether (129 g, 136 mL; 1.6 mol). The reaction mixture was then allowed to stand overnight at room temperature. Water (200 ml) was added, the organic phase was separated, washed with dilute hydrochloric acid (1: 1, 100 ml) with water (100 ml) and dilute ammonia solution (10%; 100 ml), dried over magnesium sulfate and concentrated at 40 °. C in the water pump vacuum. The product obtained is sufficiently pure for the preparation of organometallic reagents or for other synthetic uses.

c) 1-O-methoxymethyl-9-dodecinol. A solution of 10-methoxymethyl-4-chlorobutanol (prepared from 1.5 mol of 4-chlorobutanol) in 350 ml of tetrahydrofuran was added dropwise to magnesium (37.0 g; 1.5 mol) overlaid with tetrahydrofuran (50 ml) and activated with iodine (200 mg). ) and methyl iodide (0.5 mL) at such a rate that the reaction mixture boils vigorously. After the main reaction has subsided, the reaction mixture is refluxed for 1 hour. After cooling, the obtained organomagnesium compound solution is poured from unreacted magnesium, cooled in dry ice-ethanol, and copper chloride (3 g; dried at 130 ° G / 13.3 Pa) and 1-chloro-5-octine (144 g) are added. , 5 g (1 mol). The reaction mixture is allowed to warm to room temperature and is allowed to stand at this temperature until the disappearance of 1-chloro-5-octine. The control is carried out by gas chromatography and the reaction generally takes 7 days. The reaction mixture was then quenched with saturated ammonium sulfate solution (1.0 L), the organic phase separated, dried and concentrated.

d) 9-Dodecin-1-ol. The residue from c) was dissolved in methanol (1.0 L) and hydrochloric acid (20 mL) was added and the reaction mixture was heated at reflux for 3 hours. After concentration, ammonia (150 ml), water (500 ml) and ether (250 ml) were added to the residue. The organic phase is separated, washed with water, dried and concentrated. The product is isolated by distillation and a fraction boiling at 135-150 ° C / 1.2 kPa is collected. Yield 70%. 9-Dodecin-1-ol is converted to (E) -9-dodecen-1-ol by reduction with sodium in ammonia, or is converted to (Z) -9-dodecen-ol by reduction with hydrogen in the presence of a catalytic amount of ethylenediamine-deactivated nickel boride. are identical to authentic samples by gas chromatography and mass spectrometry.

Example 2

Following the procedure of Example 1, but substituting 1-O-methoxymethyl-4-chlorobutanol for an equivalent amount of 1-O-methoxymethyl-6-bromohexanol, 11-tetradecin-1-ol was prepared. The fraction boiling at 90 to 100 ° C / 6.6 Pa was collected by distillation isolation. Reduction with sodium in ammonia gives (E) -11-tetradecen-1-ol identical to gas chromatography and mass spectrometry with an authentic sample.

Example 3

Following the procedure of Example 1, but substituting 1-chloro-5-octin for an equivalent amount of 1-chloro-5-decine and substituting 1-O-methoxymethyl-4-chlorobutanol for an equivalent amount of 10-methoxymethyl-6-bromohexanol, 11-hexadecin-1 was prepared. -ol. The fraction boiling at 110 to 115 ° C was collected during the isolation by distillation.

6.6 Pa. Reduction with sodium in ammonia gives (E) -1-hexadecen-1-ol identical to gas chromatography and mass spectrometry with an authentic sample.

Example 4

The acetylenic alcohols prepared according to Examples 1 to 3 are acetylated by dropwise addition of a corresponding alcohol (1 mol) to a mixture of acetic anhydride (190 ml, 2 mol) and potassium acetate (10 g) heated in a boiling water bath, followed by heating the reaction mixture. 2 hours and then quenched by adding 50 ml of water. The mixture is concentrated at 40 ° C / 1.3 kPa, water (500 ml) and benzene (500 ml) are added to the residue. The organic phase is separated, washed with a soda solution, dried and concentrated. The product is purified by distillation.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of alkyne derivatives of formula (I) R ¹ - C ¹ -C - (CH ₂ ) _m - O - R 2 (I), wherein R ¹ is hydrogen or C 1 -C 5 alkyl, R ² is hydrogen, C 1 -C 5 alkanoyl or CH 2 OCH 3 and n is an integer from 6 to 16, characterized in that a compound of formula II is reacted R ¹ -C = C- (CH ₂ ) _n -X (II) wherein X is a halogen atom or an arylsulfonyl group having 6 to 12 carbon atoms n is an integer from 3 to 8 and R ¹ is as defined above with a compound of formula III XMg - (CH ₂ ) _p - O - CH ₂ - O - CH ₃ (III), wherein X is a halogen atom and _p is an integer from 3 to 8, in the presence of a catalytic amount of CuCl in an organic solvent such as ethereal solvents, preferably in tetrahydrofuran, at a temperature of from 0 to 30 ° C, preferably at room temperature, whereupon optionally a compound of formula I wherein R ² is CH ₂ OCH _{3 is} acid hydrolyzed to form a compound of formula I wherein R ² is an atom and optionally acylated to form a compound of formula I wherein R ² is C 1 -C 5 alkanoyl.