• 专利附录
  • 专利说明
  • 权利要求
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    • 专利摘要:
    The present invention relates to a process for accessing (E, Z) -7,9-dodecandienyl-1-acetate in two synthetic steps, with excellent yields and a selectivity greater than 70% by transformation of 2-hexenal to a new intermediate, which is then converted into (E, Z) -7,9-dodecandienyl-1-acetate.
    公开号:FR3023291A1
    申请号:FR1456322
    申请日:2014-07-02
    公开日:2016-01-08
    发明作者:Samuel Dufour；Olivier Guerret
    申请人:Melchior Material and Life Science France SAS；
    IPC主号:
    专利说明:

    [0001] The present invention relates to a process for obtaining (E, Z) -7,9-dodecandienyl-1-acetate, a sex pheromone of the eudemys of the vine, or lobesia botrana, a lepidopteran pest of the vine. This process is characterized by the use of a new intermediate 1 defined as a mixture of isomers of the general formula: ## STR3 ## where R 1 and R '1, which may be identical or different, denote an alkyl or aryl group. These compounds are alkyl-aryl, dialkyl or diaryl-hexa-1,3-dien-1-yl phosphate. For reasons of public health and the management of the agricultural potential of soils, pest management technologies are evolving towards more targeted and more environmentally friendly methods of action. As such, the use of sex pheromones to modify the behavior of insects has advantages since these pheromones are specific to each species of pest and are effective, at very low doses, in various types of strategy (trapping, sexual confusion for example). However a hindrance to the development of these technologies lies in the cost of access to active molecules. Indeed, these molecules often have many possible isomers and selective synthesis technologies are generally expensive. The main component of the sexual pheromone of the vine eudemys is (E, Z) -7,9-dodecandienyl-1-acetate. This molecule is carrier of 2 double bonds and thus has 4 possible geometric isomers recalled in the following table: 30 ......._ -..., .. ,,,, .... ' '.......' ..... ', ...', ... 7. ', ...,. O, ir- (E, Z) -7,9-dodecandiény1-1 -acetate oo (E, E) -7,9-dodecandiinyl-1-acetate o (Z, Z) -7,9-dodecandienyl-1-acetate o (Z, E) -7,9-dodecandienyl 1-acetate o Table 1: geometric isomers of 7,9-dodecandienyl-1-acetate To effectively meet the economic problem posed by the synthesis of this pheromone, the following elements should be taken into account: - Only the isomer (E , Z) is active, so it is essential to be able to prepare it for the most part.With all these isomers, the thermodynamically most stable isomer is the (E, E) isomer. Z) -7.9 dodecandienyl-1-acetate is exposed to light or free radical generators, the molecule rearranges into a mixture of these isomers in proportions 14/70/14/2 which reflect the equilibrium between the different isomers (Ideses & al. Journal of Chemical Ecology, VoL 8, No. 1, 1982, p. 973). It should be noted, however, that the 3 isomers other than (E, Z) are known not to hinder the attractiveness of the pheromone (Ideses et al., Journal of Chemical Ecology, VoL 8, No. 1, 1982, p. 195). - The isomer (E, E) is the most stable isomer and is the main inactive impurity of all known syntheses.
    [0002] It is therefore understood that a process for synthesizing the pheromone leading to the very pure active isomer, but at very high production costs, will not meet the technical-economic problem since a process leading to a lower proportion of the good isomer, but with a good overall yield and a reduced number of synthesis stages, may have a better economic efficiency and therefore allow a better development of the technology for controlling populations of lobesia botrana in the vineyards by sexual confusion. To determine the economic efficiency of a synthesis, it is therefore necessary not only to take into account the overall yield of the synthesis that reflects the economy in terms of raw material but also the number of synthesis steps that govern the cost of implementation. of said synthesis. By synthesis step, the applicant understands any chemical operation resulting in the isolation of an intermediate. The fewer the number of steps, the more economical the route of synthesis. Examination of the solutions proposed in the prior art leads to the following results: In US 3954818 the authors describe a synthesis in more than 9 stages with an unspecified yield and a purity of the pheromone close to 99%. However, it should be noted that this process is difficult to envisage industrially because of the reagents used (lithium wire, butyl lithium, disiamylborane ...). The key intermediate of this synthesis is methyl non-4-en-ynoate. In EP 3845108, the process described consists of 8 synthesis steps for an overall yield of 30% from the fourth step and a final purity of only 70%. The process is characterized by an iminophosphonate intermediate and the use of reagents unusable industrially (mercury oxide). In EP0241335, the authors describe a 5-step synthetic process with an overall yield of about 10%. The purity of the pheromone is 75% at least. The key intermediate is 1-halogeno- (E, Z) -7,9-dodecadiene. This expensive process requires pressure hydrogenation equipment. It also uses a Wittig reaction which generates large amounts of expensive triphenyl phosphine oxide to be removed. US Pat. No. 4,912,253 describes the synthesis of the pheromone of the vine eudemys by catalytic coupling to copper between a magnesium (derived from chloropentanol) and (E, Z) -2,4-heptadienyl aceate. The preparation of the acetate derivative is however difficult and this access route although convergent remains expensive. In FR 2609868, the authors report two methods for synthesizing a precursor of a pheromone analogue (Z-9-dodecen-9-ynol) via a process characterized in that the key intermediate is an alkynol protected by a tetrahydropyranyl function. The yields are similar to those of EP 0241335. In US7932410, a general method for forming long chain fatty conjugated dienes is described, and is characterized by the use of alpha-bound esters of a double bond such as isobutyrate of 1-penten-3-yl which is coupled to a Grignard reagent via catalysis based on copper complexes. This method is not applicable industrially to the synthesis of (E, Z) -7.9 dodecandienyl-1-acetate because the 1,3-heptdien-3-yl isobutyrate necessary for this synthesis is very difficult to access industrially. . The conventional synthetic methodologies known in the literature for the synthesis of the pheromone of the vine eudemys therefore use either acetylenic type intermediates (coupling via acetylides) or coupling reactions between aldehyde and phosphorus ylides, so-called reactions. from Wittig. Other more original ways have also been reported. In Alexakis & al. Tetrahedron, vol. 45, No. 2, p. 389, 1989, the authors describe an 8-step process that exploits the reactivity of epoxide functions in the presence of silicon derivatives. In Loreau et al. Chemistry and Physics, 110 (2001) p. 57, a selective synthesis route in 7 steps, is described. It is expensive because of the palladium catalysts it employs.
    [0003] In Krishnam & al, Journal of Agric. & Food chemistry, vol 50, 22, 2002, p.6366, the authors develop a synthesis in 5 steps but including the use of catalysts unusable industrially. In Franke & al. Znatursforch vol 57 p. 739 (2002) the authors report a low temperature synthesis route using sodium bis (trimethylsilyl) amide which is difficult to extrapolate. All these syntheses have low yields and have a number of steps too important to be easily industrializable. In general, the selectivity issues are regulated by a post-treatment of the reaction crude via technologies known to those skilled in the art to separate the geometric isomers. By way of example, mention may be made of silver salt-impregnated silica column chromatography or Diels Alder reaction trapping with tetracyanoethylene of compounds E, E or the preferential complexation in a urea matrix of the compounds. E, E. These additional steps are necessary if the selectivities of the synthesis methods are bad. This state of the art shows that reducing the number of synthesis steps while maximizing the selectivity of the synthesis of (E, Z) -7.9 dodecandienyl-1-acetate would allow on the one hand savings of raw materials through better performance and cost savings in production, reducing the time required for production. The Applicant has therefore found a new process in two synthetic steps allowing access to (E, Z) -7,9-dodecandienyl-1-acetate with excellent yields and a selectivity greater than 70%. This novel process is characterized by converting the readily available 2-hexenal product, according to a first step A, to the novel intermediate 1 which is then converted into (E, Z) -7.9 crude dodecandiény1-1-acetate, via a second step B, according to the following overall synthesis scheme: 0 -0-Ri 1 0 B 1) Cat, X'Mg (CH 2) 60 Mg x "2) Acylating agent 1) Base 0 II 2) XP "--- DRO 7,9-dodecadienyl acetate and that optionally (E, Z) -7,9-dodecandienyl-1-acetate is purified by methods known to those skilled in the art . Thus, the present invention is directed to a compound of the general formula wherein R1 and R'1, which may be identical or different, denote an alkyl or aryl group. In a particular embodiment, the invention relates to a compound 1 in which the alkyl group is chosen from linear or branched C1-C6 alkyls and the aryl group is chosen from phenyl, benzyl, mesityl, or tolyl. The linear or branched C1-C6 alkyl group may be chosen from methyl, ethyl, propyl, iso-propyl, butyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl and hexyl. The invention also relates to the use of a compound 1 according to the invention for the synthesis of compounds comprising a conjugated diene unit of the type: R where R represents the radical of the compound on which the conjugated diene unit is grafted. The radical R of the compound on which the conjugated diene unit is grafted may be of various hydrocarbon or carbonaceous nature, for example, and in general any radical or pattern on which it is desired to graft the conjugated dienic unit supra in question.
    [0004] Preferably, the present invention relates to the use of a compound 1 according to the present invention for the synthesis of pheromones comprising at least one conjugated radical of formula: CH3-CH2-CH = CH = CH- According to a particular embodiment the invention relates to the use of a compound 1 according to the invention as an intermediate for the synthesis of (E, Z) -7,9-dodecenyl acetate. Thus, an object of the present invention, namely step A referred to above, relates to a process for preparing compound 1 comprising: providing 2-hexenal in a suitable solvent S1, adding a strong base nucleophile at a temperature T1 between -78 ° C and 25 ° C to form the enolate, the addition, at a temperature T2, identical or different from T1, between 78 ° C and 25 ° C of a halogenophosphate of formula XP (O) (OR1) (OR1 ') where X is a halogen and R1 and R'1 denote identical or different groups chosen from a linear or branched C1-C6 alkyl, an aryl such as phenyl or benzyl , mesityl or tolyl, the recovery of compound 1 after washing and drying the organic phase. The process for the preparation of the compound 1 according to the invention is more precisely described by the following protocol: a) A 2-hexenal equivalent diluted in 2 to 60 volumes of solvent or a mixture is prepared in a stirred reactor. solvent mixture S1. The temperature of the reaction medium is brought to a temperature T1 of between -78 ° C. and 25 ° C., and then 1 to 2 equivalents of a strongly nucleophilic strong base are added, such as a hindered alcoholate, a hindered amide or an amidine. b) Then adding to the reaction medium, at a temperature T2 of between -78 ° C. and 25 ° C., optionally identical to T1, the alkyl or aryl halophosphate of general formula: XP (O) (OR1) (OR'i) in which R1, R'1, which are identical or different, are linear or branched C1-C6 alkyl or aryl groups and X is a halogen atom, preferably chlorine. The halophosphate is added at 1 to 2 equivalents to 2-hexenal. The linear or branched C1-C6 alkyl group may be chosen from methyl, ethyl, propyl, iso-propyl, butyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl and hexyl. The aryl group is selected from phenyl, benzyl, mesityl, or tolyl The temperature at which the compound 1 is formed is stirred at the temperature T2. This product is in fact a mixture of the geometric isomers (E, E), (E, Z), (Z, E) and (Z, Z), whose ratio of isomers determines that of the whole process. In a preferred embodiment, the process for synthesizing compound 1 according to the invention is characterized in that the solvent S1 is selected from the group consisting of tetrahydrofuran (THF), methyl tetrahydrofuran (MeTHF), tetramethylethylenediamine ( TM E DA), tetrahydropyran, dimethoxyethane (DME), diethyl ether, methyl-tert-butyl ether (MTBE), very polar nitrogen-containing solvents such as dimethylformamide (DMF), N-methylpyrrolidinone (NMP), N , N'-Dimethylpropylene urea (DMPU), methylcyclohexane (MeCy), alkanes of less than 8 carbon atoms, aromatic solvents such as toluene and mixtures thereof. Suitable mixtures are THF / NMP, THF / DMF, THF / DMPU, THF / TMEDA, MTBE / NMP, MeCy / NMP, for example. According to a particular variant of the invention, the method of synthesis of the compound 1 described here is characterized in that the identical or different temperatures T1 and T2 are between -40 ° C. and 15 ° C.
    [0005] Even more particularly, the process for synthesizing compound 1 according to the invention is characterized in that the same or different temperatures T1 and T2 are between -20 ° C. and 0 ° C. The method for synthesizing compound 1 according to the present invention is characterized in that the weak nucleophilic strong base is selected from the group consisting of potassium or sodium terbutanolate, sodium or potassium diisopropyleamide, sodium hexamethyldisilylazane or of potassium, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU).
    [0006] The aqueous treatment of the organic solution serves to remove some of the solvents contained in S1 before the subsequent metal coupling, as well as the salts formed by this step and the excess of reagents. The solution obtained is therefore a solution of compound 1 in a solvent or a mixture of solvents S2. The organic phase is dried so as to be used directly according to step B mentioned above or evaporated under reduced pressure to isolate intermediate 1. Also, the present invention relates to a process for preparing (E, Z) -7, 9-dodecandiene-1-acetate, representing the step B indicated above, comprising the following steps: supply of the product 1 in a solvent S2, addition of a catalytic system containing at least one iron atom at the oxidation degree III, addition, at a temperature T3 of between -20 ° and 60 ° C, of the compound of general formula X'Mg- (CH2) 6-O-MgX "where X 'and X", which are identical or different, designate a halogen atom, addition of an acetylating agent, recovery of (E, Z) -7,9-dodecandienyl-1-acetate after washing and evaporation of the organic solvents. In a particular embodiment, the process for preparing (E, Z) -7,9-dodecandiene-1-acetate is characterized in that the solvent S 2 is selected from the group consisting of THF, MeTHF, MeCy, diethyl ether, methyl terbutyl ether (MTBE), 1,2-dimethoxyethane and mixtures thereof.
    [0007] Preferably, S 2 is a mixture of ethers or alkanes and even more preferably, S 2 is selected from the group consisting of THF, MeCy, MTBE and MeTHF. In a preferred embodiment, the process for the preparation of 7,9-dodecandienyl-1-acetate according to the present invention is characterized in that the temperature T3 is between 0 ° C. and 60 ° C., particularly between 0 ° C. and 30 ° C. The process for preparing (E, Z) -7,9-dodecandylene-1-acetate according to the present invention is characterized in that the Cat catalyst system is selected from the group consisting of iron trihalides, iron triacetate , iron triacetylacetonate, iron (III) nitrate, iron (III) phosphate optionally in the presence of ligands chosen from phosphorus or nitrogen ligands. In a particular embodiment of the process according to the present invention, the acetylating agent is selected from the group consisting of acetoyl halides, acetic anhydride and alkyl acetate. The process for the preparation of (E, Z) -7,9-dodecandylene-1-acetate according to the present invention, namely step B as indicated above, is more precisely detailed below. a) The solution of compound 1 in S 2 is brought into the presence of 0.5 mol% to 2 mol% of a Cat catalyst system which contains an iron atom of oxidation degree III. The mixture is kept under stirring at a temperature T3 of between -20 ° and 60 ° C, particularly between -5 ° C and 25 ° C. A solution of solvent S3 containing the compound of general formula X'Mg- (CH2) 6-OMgX ", in which X 'and X", which are identical or different, designate a halogen atom, particularly a Cl or Cl atom, is then added. Br Br Br, from 0.95 to 1.5 equivalent compared to the hexenal. The reaction leads to a solution of (E, Z) -7,9-dodecadienadate. b) An acetylation reagent such as acetoyl halides, acetic anhydride or an alkyl acetate is then added at 1.5 to 5 equivalents. c) The reaction medium is then washed with an acidic aqueous solution at a pH of between 2 and 6 and then with a solution at pH between 7 and 9. The organic phase is recovered and then concentrated under vacuum to recover the (E, Z) Crude 7,9-dodecandanyl-1-acetate.
    [0008] Depending on the required purity, (E, Z) -7,9-dodecandanyl-1-acetate can be purified. The product is purified by vacuum distillation. In a particular embodiment, the solvent S3 of the compound of the general formula X'Mg- (CH2) 6-OMgX "may be chosen from the group consisting of THF and MeTHF, and mixtures thereof. using a method of the art to reduce the importance of the (E, E) -isomer, for example, by using the preferential complexation of this isomer in a urea matrix (see Leadbetter et al., Journal of Chemical Ecology, Vol 5). No. 1, 1979, page 101) or by preferential reaction with tetracyanoethylene In a variant of the process, it is possible to proceed with the sequence of step A and of step B without isolating the The present invention thus relates to a process for the preparation of 7,9-dodecandienyl-1-acetate, in particular (E, Z) 7,9-dodecandienyl. -1-acetate, from 2-hexenal through the succession of stages s A and B. With this process, the Applicant gets yields and production cycle times much better than anything known to those skilled in the art. The metal-catalyzed magnesium transfers on phosphate enols employed in step B of the process are described in the literature (see Cahiez et al., J. Org Chem 2008, 73, 6871 and Org. Vol.10, No. 12, 2008, 2389). Furthermore, it appears that compound 1 is a new chemical compound easily accessible from 2-hexenal which provides access to the main component of the vine eudemys pheromone in a single step.
    [0009] Reading the work of Cahiez further shows that these reactions are very selective when the starting aldehyde is 2-butenal or 2-pentenal but that this selectivity is lost for a number of carbon atoms higher than 5. It was therefore not obvious that an aldehyde with 6 carbon atoms leads to a type 1 intermediate with good selectivities (> 80%). As the new compound 1 provides access to (E, Z) -7,9-dodecadienyl acetate, it also allows access to diene derivatives of general formula: Nprer44./R where R represents the radical of the compound on which is grafted conjugated diene unit, for example a hydrocarbon radical, carbon or any other radical or pattern on which it may be desired to graft said conjugated diene unit.
    [0010] Examples: Raw materials and solvents are the raw materials found commercially at Sigma Aldrich. The analytical method consists of Gas Chromatography (GC) analysis on an HP 5890 Series II equipped with an FID detector. The chromatographic column is an Innowax 30m column, 0.25 mm, 0.25 μm, the carrier gas being helium. The oven follows the following temperature profile: T0 = 150 ° C, initial time 10 min. Gradient 20 ° / min; Final temperature: 200 ° C. Duration 7 min. The injector is at 250 ° C, the detector at 300 ° C. The injected volume is 1 μl. The concentration of the sample is 4 g / l in ethyl acetate (AcOEt). The reactions are carried out in a 2 L jacketed glass reactor equipped with a low temperature cooling system and the distillations are carried out by means of a glass column of 10 theoretical trays.
    [0011] EXAMPLE 1 Preparation of Key Intermediate 1 with R1 and R'1 = Ethyl 50 g (0.51 mol) of 2-hexenal diluted in 10 volumes of a mixture are prepared in the reactor equipped with stirring. 2 of THF and NMP (S1), the temperature of the reaction medium is lowered to a temperature T1 of -15 ° C., 69 g (0.61 mol) of potassium tert-butanolate are then added. After one hour, 97 g (0.56 moles) of diethyl chlorophosphate are added to the reaction medium at the temperature of T2, still at -15 ° C. The reaction is stirred for 1 hour then the product formed is isolated by washing with a sodium hydroxide solution which makes it possible to obtain 500 g of a solution of the enolphosphate in THF. The solution is dried over MgSO4 to a residual water content of less than 0.1%, the enolphosphate content is determined by gas chromatography. This solution can be used as is in the following examples. The isolation of compound 1 is carried out by partial evaporation of the solvents. 105 g of diethyl-hexa-1,3-dien-1-yl phosphate are recovered in the form of a mixture of 2 isomers in the following ratio: Z, Z-diethyl-hexa-1,3-dien-1 phosphate: <1 Z, E-diethyl-hexa-1,3-dien-1-yl phosphate: <1% E, Z-diethyl-hexa-1,3-dien-1-yl phosphate: 72% E, E-diethyl-hexa-1,3-dien-1-yl phosphate: 27% Characterization: Retention time by gas phase chromatography: Z, Z-diethyl-hexa-1,3-dien-1-yl phosphate: 13.96 mm; Z, E-diethyl-hexa-1,3-dien-1-yl phosphate: 14.27 mm; E, Z-diethyl-hexa-1,3-dien-1-yl phosphate: 14.43 mm; E, E-diethylhexa-1,3-dien-1-yl phosphate: 15.27 mm. 1H NMR (8 ppm, CDCl3): 6.65 (1H, doublet of doublet, CH); 6.26 (1H, triplet, CH); 5.79 (1H, triplet, CH); 5.4 (1H, doublet of triplets), 4.15 (4H, triplet, OCH 2), 2.11 (2H, solid, CH 3 CH 2), 1.33 (6H, triplet, CH 3 CH 2 O), 0.97 (3H, triplet, CH3CH2CH). EXAMPLE 2 Synthesis of (E, Z) 7,9-dodecandienyl-1-acetate 1.8 g (5.1) mmol of iron tri (acetylacetonate) are then added to the intermediate solution of example 1, and then 0.61 mol of BrMg- (CH 2) 6-OMgBr in 1.6 mol / mol solution are gently poured into the reactor. L in the MeTHF. During this addition, the reaction medium is maintained at the temperature T3 of 25 ° C. After two hours, 260 g of acetic anhydride is added to the reaction medium, which is stirred at room temperature, until complete conversion of the alcoholate formed during the coupling to iron. The reaction medium is then washed with a solution of 0.01 molar hydrochloric acid and then with a solution of sodium carbonate at a pH of 8. The organic phase is recovered and then concentrated under vacuum to recover 7,9-dodecandienyl-1. crude acetate (88 g assayed at 90% of chemical purity and in an E, Z / Z, Z isomer ratio of 76%). That is a gross yield of 69% compared to the hexenal.
    [0012] The crude is distilled under high vacuum to yield 75 g of 7,9-dodecandanyl-1-acetate with 98% chemical purity and an E, Z isomer content of 76%. That is a yield of 66% compared to the hexenal. Enrichment of the isomer E, Z: The 75 g obtained are mixed with 130 g of urea in 800 ml of methanol.
    [0013] The mixture is left standing for 3 hours. The suspension is filtered and the residue is washed twice with 100 ml of diethyl ether. The washing fractions are combined with the filtrate and then evaporated under reduced pressure until the solvents are completely evaporated. 61 g of 7,9-dodecandienyl-1-acetate with a chemical purity of 98% and with a content of 90% of the E, Z isomer are obtained. Examples 3 to 20: In all the following examples, the experimental protocol of Examples 1 and 2 is used, varying the following parameters: 51: dilution solvent for hexenal. S 2: diethyl-hexa-1,3-dien-1-yl-phosphate dilution solvent. S3: diluting solvent for the magnesium compound - X ': halide of the compound X'Mg- (CH2) 6-OMgX' - T1: deprotonation temperature of the hexenal - T2: diethyl-hexa-1 synthesis temperature, 3-dien-1-yl-phosphate - T3: organomagnesium coupling temperature - N1 = number of moles of potassium terbutanolate / number of moles of hexenal - N2 = number of moles of diethyl chlorophosphate / number of moles of hexenal N 3 = number of moles of magnesium / number of moles of hexenal The parameters varying in the examples are summarized in Table 1. EXAMPLE S1 * S2 S3 X 'T1 T2 T3 N2 N4 N4 (mol) (mol) (mol) 3 THF / NMP THF THF Br -78 -78 0 1,2 1,1 1,2 (17/12) 4 THF / NMP THF MeTHF Br -70 -78 0 1,2 1,2 1,2 (36/12 ) THF / NMP THF MeTHF Br -55 -78 0 1,1 1,1 1,2 (36/17) 6 THF / DMPU THF MeTHF Br -35 -78 0 1,2 1,1 1,2 (36 / 17) 7 THF / NMP THF MeTHF Br -25 0 1,2 1,1 1,2 (36/17) 8 THF / NMP THF MeTHF Br -15 0 0 1,2 1,1 1,2 (36) / 17) 9 THF / NMP THF MeTHF Br -15 -15 0 1,2 1,1 1,2 (36/17) 10 THF / DMPU THF MeTHF Br -15 -15 0 1,2 1,1 1,2 (36/17) 11 THF / TMEDA THF MeTHF Br -15 -15 0 1,2 1,1 1,2 (36/17 ) 12 THF / NMP THF MeTHF Br -15 -10 0 1,2 1,1 1,2 (36/17) 13 THF / NMP THF MeTHF Br -15 0 0 1,2 1,1 1,2 (36 / 17) 14 MTBE / NMP MTBE MeTHF Br -15 -15 1,2 1,1 1,2 (36/17) MeCy / NMP MeCy MeTHF Br -15 -15 0 1,2 1,1 1,2 ( 36/17) 16 MeCy / NMP MeCy MeTHF Br -15 -15 1,2 1,1 1,2 (10/2) 17 THF / DMF THF MeTHF Br -15 -15 25 1,2 1,1 1, 2 (36/12) 18 DMF / NMP THF MeTHF Br -15 -15 1,2 1,1 1,2 (14/2) 19 DMF / NMP THF THF Br -15 -15 25 1,2 1,1 1.2 (14/2) DMPU / NMP THF THF Br -10 -10 1,2 1,1 1,2 (14/2) 21 DMPU / NMP THF THF Br -10 -10 1,2 1 , 1 1.2 (2/2) 22 NMP 5V THF THF -5 -5 25 1.2 1.1 1.2 23 NMP 5V THF THF -5 0 25 1.2 1.1 1.2 * the mixture of solvent is indicated: the figures in parentheses denote the respective volumes of the solvent components relative to the hexenal. The crude yield (Rb) of each example reflects the crude molar yield before distillation.
    [0014] The ratio Rb (E, z) denotes the proportion of the E, Z isomer with respect to the E, E isomer. The data Rd and Rd (E, z) respectively denote the molar yield, the proportion of the E, Z isomer with respect to the E, E isomer after the purification step. These results for each example are summarized in FIG. Table 2: Example Rb (%) Rb (E, z) (%) Rd (%) Rd (E, z) (%) 3 63 80 61 85 4 62 80 60 85 59 79 50 86 6 61 74 51 86 7 59 77 51 82 8 61 74 52 81 9 59 74 49 81 49 57 ** ** 11 42 66 ** ** 12 59 74 24 91 13 44 63 ** ** 14 51 74 ** ** 62 74 49 81 16 44 65 ** ** 17 65 74 52 80 18 14 72 ** ** 19 14 72 ** ** 38 66 ** ** 21 38 66 ** ** 22 25 57 ** ** 23 25 57 ** ** ** the experiments have not been purified 5
    权利要求:
    Claims (14)
    [0001]
    REVENDICATIONS1. Compound of general formula wherein R1 and R'1, which may be identical or different, denote an alkyl or aryl group.
    [0002]
    2. Compound according to claim 1 wherein the alkyl group is selected from linear or branched C1-C6 alkyls, the aryl group is selected from phenyl, benzyl, mesityl, or tolyl.
    [0003]
    3. Use of a compound 1 according to one of claims 1 to 2, for the synthesis of diene compound of general formula: R wherein R represents the radical of the compound on which is grafted the conjugated diene unit.
    [0004]
    4. Use of a compound 1 according to one of claims 1 to 2, for the synthesis of pheromones comprising at least one conjugated radical of formula: CH3-CH2-CH = CH = CH-
    [0005]
    5. Use of a compound 1 according to one of claims 1 to 2 as an intermediate for the synthesis of (E, Z) -7,9-dodecadiene-1-acetate.
    [0006]
    6. A process for the preparation of compound 1 comprising the steps of: providing hexenal in a suitable solvent S1, adding a weak nucleophilic strong base at a temperature T1 between -78 ° C and 25 ° C to form the enolate, addition, at a temperature T2, identical to or different from T1, between -78 ° C and 25 ° C of a halophosphate of formula: XP (0) (OR1) (OR1 ') where X is a halogen and R1 and R '1 denote identical or different groups chosen from a linear or branched C1-C6 alkyl, an aryl such as phenyl, benzyl, mesityl or tolyl, - recovery of compound 1 after washing and drying of the organic phase.
    [0007]
    7. Process according to claim 6, characterized in that the solvent S1 is chosen from the group consisting of tetrahydrofuran (THF), methyl tetrahydrofuran (MeTHF), tetramethylethylenediamine (TMEDA), tetrahydropyran, dimethoxyethane (DME) and diethyl ether, methyl-tert-butyl ether, very polar nitrogen-containing solvents such as dimethylformamide (DMF), N-methylpyrrolidinone (NMP), N, N'-dimethyl propylene urea (DMPU), methylcyclohexane (MeCy), alkanes of less than of 8 carbon atoms, aromatic solvents such as toluene and mixtures thereof.
    [0008]
    8. Method according to one of claims 6 or 7, characterized in that the same or different temperatures T1 and T2 are between -40 ° C and 15 ° C.
    [0009]
    9. Process according to claims 6 to 8, characterized in that the same or different temperatures T1 and T2 are between -20 ° C and 0 ° C.
    [0010]
    10. Process according to claims 6 to 9, characterized in that the weak nucleophilic base is selected from the group consisting of sodium or potassium terbutanolalte, sodium or potassium diisopropyleamide, sodium or potassium hexamethyldisilylazane 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU).
    [0011]
    11. Process for the preparation of (E, Z) -7,9-dodecandiene-1-acetate, comprising the following steps: supply of the product 1 in a solvent S 2, addition of a catalytic system containing at least one iron atom at degree of oxidation III, addition, at a temperature T3 of between -20 ° and 60 ° C, of the compound of general formula X'Mg- (CH2) 6-OMgX "where X 'and X", which are identical or different, designate a halogen, addition of an acetylating agent, recovery of (E, Z) -7,9-dodecandiene-1-acetate after washing and evaporation of the organic solvents.
    [0012]
    12. Process according to claim 11, characterized in that the solvent S2 is chosen from the group consisting of THF, MeTHF, methylcyclohexane (MeCy), diethyl ether, methyl terbutyl ether, 1,2-dimethoxyethane and their mixtures.
    [0013]
    13. The method of claims 11 and 12 characterized in that the temperature T3 is between 0 ° C and 60 ° C.
    [0014]
    14. Process according to Claims 11 to 13, characterized in that the Cat catalyst system is chosen from the group consisting of iron trihalides, iron triacetate, iron triacetylacetonate, iron (III) nitrate and phosphate. of iron (III), optionally in the presence of a ligand chosen from phosphorus or nitrogen ligands.
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    同族专利:
    公开号 | 公开日
    CN106660928A|2017-05-10|
    FR3023291B1|2016-07-22|
    US9975912B2|2018-05-22|
    WO2016001383A1|2016-01-07|
    CN106660928B|2021-10-22|
    ES2699151T3|2019-02-07|
    EP3164408B1|2018-09-12|
    EP3164408A1|2017-05-10|
    US20170137447A1|2017-05-18|
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    US3845108A|1973-08-31|1974-10-29|W Roelofs|Trans-7-cis-9-dodecadien-1-yl acetate|
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    JPH0360808B2|1986-03-19|1991-09-17|Shinetsu Chem Ind Co|
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    FR3063729B1|2017-03-10|2019-06-07|Universite de Bordeaux|NOVEL ISOMERIC COMPOSITION OF 7,9-DODECADIENYL-1-ACETATE AND METHOD OF MAKING SAME|
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    优先权:
    申请号 | 申请日 | 专利标题
    FR1456322A|FR3023291B1|2014-07-02|2014-07-02|NEW PROCESS FOR MANUFACTURING-7.9 DODECANDIENYL-1-ACETATE|FR1456322A| FR3023291B1|2014-07-02|2014-07-02|NEW PROCESS FOR MANUFACTURING-7.9 DODECANDIENYL-1-ACETATE|
    ES15733755T| ES2699151T3|2014-07-02|2015-07-02|New manufacturing process for-7,9-dodecadienil-1-acetate|
    US15/323,287| US9975912B2|2014-07-02|2015-07-02|Method for producing -7,9-dodecadienyl-1-acetate|
    CN201580036484.8A| CN106660928B|2014-07-02|2015-07-02|Novel process for the preparation of-7, 9-dodecadienyl-1-acetate|
    PCT/EP2015/065152| WO2016001383A1|2014-07-02|2015-07-02|Novel method for producing -7,9 dodecadienyl-1-acetate|
    EP15733755.1A| EP3164408B1|2014-07-02|2015-07-02|Novel method for producing -7,9 dodecadienyl-1-acetate|
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