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WO2007026654A1 - Énamide et son procédé de production, et diénamide et son procédé de production - Google Patents

Énamide et son procédé de production, et diénamide et son procédé de production Download PDF

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Publication number
WO2007026654A1
WO2007026654A1 PCT/JP2006/316892 JP2006316892W WO2007026654A1 WO 2007026654 A1 WO2007026654 A1 WO 2007026654A1 JP 2006316892 W JP2006316892 W JP 2006316892W WO 2007026654 A1 WO2007026654 A1 WO 2007026654A1
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Prior art keywords
producing
enamide
group
genamide
reaction
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Japanese (ja)
Inventor
Takeaki Mitsudo
Yasuyuki Ura
Teruyuki Kondo
Kenji Wada
Hiroshi Tsujita
Shingo Matsuki
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Kyoto University NUC
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Kyoto University NUC
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D223/08—Oxygen atoms
    • C07D223/10—Oxygen atoms attached in position 2
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/821—Ruthenium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/60—Ring systems containing bridged rings containing three rings containing at least one ring with less than six members
    • C07C2603/62—Ring systems containing bridged rings containing three rings containing at least one ring with less than six members containing three- or four-membered rings
    • C07C2603/64—Ring systems containing bridged rings containing three rings containing at least one ring with less than six members containing three- or four-membered rings having a tricyclo[2.2.1.0(2,6)]heptstructure

Definitions

  • the present invention relates to an enamide (N-alkylamide) and a method for producing the same, and in particular, by a co-dimeric reaction between a novel enamide, N-buramide and an alkene using a ruthenium complex catalyst.
  • the present invention relates to a novel process for producing enamide.
  • the present invention also relates to genamide and a method for producing the same, and in particular, genamide is produced by a co-dimerization reaction between novel genamide, N-vinylamide and alkyne using a ruthenium complex catalyst.
  • Enamides containing N-alkyllactams can be easily derived, for example, from protected amines such as pyridones, N-acylimidium cations, and are useful as synthetic intermediates for pharmaceuticals and the like.
  • ratatas generally become polyamides by ring-opening polymerization. Therefore, by using N-alkenyllatata as a starting material, it is possible to synthesize polyamides having various side chains. These polyamides may become new functional materials.
  • a method for producing enamide (1) a method in which a Grignard reagent is allowed to act on -tolyl and then treated with acetic anhydride (for example, Non-Patent Document 1), (2) ketone and hydroxylamine hydrochloride A method of producing oxime from a salt and reductive acetylation in acetic anhydride in the presence of iron powder (for example, Non-Patent Document 2), (3) a method of condensing a ketone and acetamide under acidic conditions (for example, Non-Patent Document 3), (4) A method of condensing a ketal and acetamide or a powerful rubamate in the presence of a diphosphorus hydrochloride (for example, Non-Patent Document 4), (5) A ketal and an amide under acidic conditions.
  • a condensation method for example, Patent Document 1 has been proposed.
  • genamides are a group of compounds useful in organic synthetic chemistry. For example, by using genamides as substrates for Diels-Alder reactions, they can be converted into various unsaturated amide compounds with ring structures and arlin derivatives. Is possible.
  • Patent Document 1 Japanese Patent Laid-Open No. 2002-308842
  • Non-patent literature l J. Organometal. Chem. (1975), 90, 353.
  • Non-Patent Document 2 J. Org. Chem. (1998), 63,6084.
  • Non-Patent Document 3 J. Org. Chem. (1965), 30, 123.
  • Non-Patent Document 4 Manual Des Sciences (1935), 560, J. Chem. Soc. Perkin Trans 1 (1988), 2 185.
  • Non-Patent Document 5 Org. Lett. (2003), 5, 67.
  • Non-Patent Document 6 J. Org. Chem. (2003), 68, 6639.
  • Non-Patent Document 7 Org. Lett. (2002), 4,803.
  • the conventional method for producing genamide also includes yield, economic efficiency, safety, simplicity, and raw material selection. In terms of sex, it had the same problems as with Enamide.
  • the present invention has been made to solve the above-mentioned problems, and an object of the present invention is to easily produce an enamide using a starting material that is less expensive than the prior art and without producing a by-product.
  • An object of the present invention is to provide a novel method for producing enamide.
  • Another object of the present invention is to provide a novel enamide.
  • Still another object of the present invention is to provide a novel method for producing genamide, which can easily produce genamide using a starting material which is cheaper than the conventional one.
  • Still another object of the present invention is to provide a novel genamide.
  • the method for producing enamide according to claim 1 comprises reacting N-Buramide with an alkene in the presence of a ruthenium complex catalyst containing 0-valent or divalent ruthenium, It is characterized by producing enamide.
  • the method for producing genamide according to claim 27 comprises reacting N-buramide with an alkyne in the presence of a ruthenium complex catalyst containing 0-valent ruthenium, It is characterized by manufacturing.
  • N-vinylamide and alkene are cheaper than conventional starting materials in the presence of a ruthenium complex catalyst containing zero-valent or divalent ruthenium.
  • Enamide is useful as a synthetic intermediate or polymer monomer for pharmaceuticals, and according to the production method of the present invention, these useful substances can be produced industrially.
  • enamides having no substituent on the olefinic carbon adjacent to the amide nitrogen, which are difficult to produce by the prior art can be produced industrially.
  • Genamide is also useful as a synthetic intermediate in the same manner as enamide, and according to the production method of the present invention, these useful substances can be produced industrially.
  • the production method of the present invention it is possible to industrially produce genamides having no substituent on the olefin carbon adjacent to the amide nitrogen, which is difficult to produce by the prior art.
  • the method for producing enamide according to the present invention is to produce enamide by reacting (co-dimerization) of N-buramide and alkene in the presence of a ruthenium complex catalyst containing 0-valent or divalent ruthenium. .
  • Enamide is a very useful compound that can be used as a synthetic intermediate or a polymer monomer of a pharmaceutical product. According to the production method of the present invention, enamide can be easily produced using N-vinylamide and alkene, which are cheaper than conventional starting materials, without producing a by-product.
  • enamide is selectively produced as a by-product of the regioisomer. That is, the production of the present invention According to the method, an enamide in which an alkene is introduced in a chain form on the side different from the amide nitrogen with respect to the carbon double bond of the bull group of N-vinylacetamide is produced with high yield and high selectivity. Can be built.
  • enamides having no substituent on the olefin carbon adjacent to the amide nitrogen which are difficult to produce by the prior art, can be produced industrially.
  • the structure of the novel enamide found in the process of studying the production method of the present invention is shown in the following general formula (3).
  • R 2 independently represents a hydrogen atom, an alkyl group, or an aryl group.
  • R 1 and R 2 may be connected to each other to form a ring.
  • R 1 and R 2 represent a methylene group having 3 to 5 carbon atoms.
  • R 4 and R 6 each independently represent a hydrogen atom, an alkyl group, an aryl group, an acyl group, an alkoxy group, a phenyl group, or an arylcarbonyl group.
  • R 4 and R 6 may be connected to each other to form a ring.
  • Ruthenium a Group 8 transition metal element in the periodic table, can take a variety of acid and oxygen states.
  • a ruthenium complex in which the acid state of ruthenium is 0 or 2 is used as a catalyst.
  • the structure of the ruthenium complex catalyst is represented by the following chemical formula (1).
  • ⁇ L 2 and L 3 each represent a neutral or arion ligand
  • L 1 is a monodentate ligand
  • L 2 is a bidentate ligand
  • L 3 is a tridentate ligand Represents.
  • m, and n each represent an integer of 0 or more.
  • the neutral ligand or the eron ligand contains a ligand that is easily dissociated during the reaction.
  • Examples of the eron ligand include a polyenyl group such as a cyclotagel group. Among these, a cyclotactenyl group is particularly preferable.
  • the neutral ligand may be a monodentate, bidentate, or tridentate ligand! / ⁇ .
  • Neutral ligands include dimethyl fumarate (abbreviation dmftn), alkenes such as methyl acrylate, 1,5-cyclooctagen (abbreviation cod), 1,3,5-cyclootatatriene (abbreviation cot) ), Aromatic compounds such as benzene, carbon monoxide, and the like. Among these, dimethyl fumarate (dm & i), 1,5-cyclooctadiene (cod), and 1,3,5-cyclootatriene (cot) are preferable. Dimethyl fumarate and carbon monoxide are monodentate ligands, 1,5-cyclooctagen is a bidentate ligand, and 1,3,5-cyclootatatriene is a tridentate ligand. It is.
  • ruthenium complex catalyst examples include Ru (cod) (cot), Ru (cot) (dmftn), R
  • Ru (cod) (cot) and Ru (cot) (dmftn) are preferred because of their excellent catalytic activity.
  • the ruthenium complex catalyst described above is composed of ruthenium (III) chloride trihydrate (RuCl ⁇ 3 ⁇ ⁇ ).
  • Ru (codXcot) is obtained by reacting ruthenium (III) chloride trihydrate, 1,5-cyclooctadiene and zinc powder under methanol reflux. Synthesized.
  • N-butyramide N-vinylamide represented by the following general formula (1) can be used.
  • R 2 independently represents a hydrogen atom, an alkyl group, or an aryl group.
  • R 1 and R 2 may be connected to each other to form a ring.
  • R 1 and R 2 When R 1 and R 2 are connected to each other to form a ring, R 1 and R 2 represent a methylene group having 3 to 5 carbon atoms.
  • Examples of the alkyl group representing R 2 include a lower alkyl group having 1 to 4 carbon atoms such as a methyl group and an ethyl group.
  • Examples of the aryl group representing R 1 R 2 include a phenol group. From the viewpoint of reaction yield, R 2 is particularly preferably a methyl group.
  • N-alkyl-N-Buramide such as N-methyl-N-Bulacetoamide, N-Bubutyrolatatam or N-Bilecaprolacta as the above N-Buramide N-Burratatum such as Mu can be used.
  • alkene an alkene represented by the following general formula (2) can be used.
  • R 3 to R ° each independently represent a hydrogen atom, an alkyl group, an aryl group, an acyl group, an alkoxy carbo ol group, or an aryl carbo yl group.
  • R 4 and R 6 can be connected to each other to form a ring! /, Or even! /.
  • Examples of the alkyl group representing R 3 to R 6 include a methyl group and an ethyl group.
  • Examples of aryl groups representing R 3 to R 6 include a phenol group.
  • Examples of the acyl group representing R 3 to R 6 include a acetyl group and a propiol group.
  • Examples of the alkoxy carbo group representing R 3 to R 6 include a methoxy carbo ol group, an ethoxy carbo ol group, and a t-butoxy carbonyl group.
  • Examples of the aryloxycarbonyl group representing R 3 to R 6 include a phenylcarboxyl group.
  • R 3 is preferably a hydrogen atom or an alkoxy carbo group! /.
  • R 4 is particularly preferably a hydrogen atom or a hydrogen atom which is preferably an alkoxycarbonyl group.
  • R 6 is preferably an acyl group, an alkoxy carbo group or an aryl carboxy group, and particularly preferably an alkoxy carbo group. When R 6 is an acyl group or an alkoxycarbonyl group, the reaction yield is improved.
  • the above alkenes include aliphatic alkenes such as ethylene, ⁇ , ⁇ -unsaturated ketones such as ethyl vinyl ketone and methyl vinyl ketone, methyl acrylate, ethyl acrylate, and butyl acrylate.
  • aliphatic alkenes such as ethylene, ⁇ , ⁇ -unsaturated ketones such as ethyl vinyl ketone and methyl vinyl ketone, methyl acrylate, ethyl acrylate, and butyl acrylate.
  • ⁇ -unsaturated carboxylic acid esters such as dimethyl maleate and jetyl maleate
  • electron-deficient alkenes such as ⁇ , j8-unsaturated carbonyl compounds are preferable. Electron-deficient alkenes are more reactive and improve the reaction yield.
  • R 4 and R 6 are As the alkene linked to form a ring, 2-norbornene or the like can be used.
  • the above-mentioned co-dimerization reaction proceeds by adding a reaction raw material, a ruthenium complex catalyst, and a solvent to a reaction vessel, and heating and stirring the obtained reaction solution. After completion of the reaction, the target compound can be obtained by removing the solvent and isolating the product.
  • the reaction solvent is more preferably a polar solvent having a high boiling point, preferably a high boiling solvent.
  • the reaction temperature is important in the present invention, and the reaction yield is remarkably improved by setting the reaction temperature to 160 ° C. or higher.
  • the reaction temperature can be set high and the reaction can be carried out under normal pressure.
  • the high boiling point solvent is a solvent having a boiling point of 150 ° C. or higher at normal pressure.
  • Examples of such high-boiling solvents include N, N-dimethylacetamide (DMA; boiling point 165 ° C), N, N-dimethylformamide (DMF; boiling point 153 ° C), diethylene glycol dimethyl ether ( Diglyme; boiling point 162 ° C), 1-hexanol (boiling point 157 ° C) and the like.
  • DMA N-dimethylacetamide
  • DMF N-dimethylformamide
  • Diglyme boiling point 162 ° C
  • 1-hexanol butylene glycol dimethyl ether
  • the amount of the solvent is adjusted so that the concentration of the catalyst in the solvent is about 0.003 to 0.03 mol Z liter, preferably about 0.007 mol Z liter.
  • concentration of the catalyst in the solvent is about 0.003 to 0.03 mol Z liter, preferably about 0.007 mol Z liter.
  • the reaction temperature is appropriately set according to the boiling point of the solvent and the like. From the viewpoint of shortening the reaction time and improving the reaction yield, the reaction temperature is preferably 140 ° C or higher. However, when the reaction temperature exceeds 170 ° C, the yield decreases. Therefore, the reaction temperature is more preferably in the range of 140 ° C to 170 ° C, and more preferably in the range of 160 ° C to 170 ° C. By setting the reaction temperature in the range of 160 ° C to 170 ° C, the reaction yield is remarkably improved.
  • the reaction time is appropriately set according to the reaction raw material (substrate), but when the reaction temperature is in the range of 160 ° C to 170 ° C, the reaction time is preferably about 3 hours.
  • the reaction vessel it is preferable to use a corrosion-resistant glass vessel.
  • the reaction is preferably performed in an inert gas atmosphere.
  • inert gas include nitrogen gas and argon gas. Can be used.
  • the reaction is preferably carried out under pressure using a stainless steel pressure-resistant autoclave.
  • the pressure of the alkene in the reaction vessel is preferably 0.5 to 2 MPa, and particularly preferably IMPa.
  • the molar ratio of N-buramide to alkene is preferably in the range of 1: 1 to 1:50, more preferably in the range of 1: 1 to 1: 5. By setting the reaction molar ratio within the above range, the reaction yield and selectivity are further improved.
  • the addition amount of the ruthenium complex catalyst is preferably in the range of 1 mol% to 5 mol% with respect to N-vinylamide, more preferably around 2 mol%.
  • a chain enamide is formed in a high yield without the by-product of the regioisomer. That is, an enamide in which an alkene is introduced in a chain form on the side different from the amide nitrogen is produced with high selectivity with respect to the carbon double bond of the N-buluacetoamide carbon.
  • Confirmation of the target compound and reaction yield can be carried out using ordinary analytical means such as gas-liquid chromatography (GLC). After completion of the reaction, the solvent is removed from the reaction solution, and the target compound is isolated from the residue. Examples of means for isolating the target compound include recycle preparative high performance liquid chromatography (recycle preparative HPLC) and distillation.
  • the method for producing genamide of the present invention is to produce genamide by reacting (co-dimerization) of N-buluamide with an alkyne in the presence of a ruthenium complex catalyst containing 0-valent ruthenium.
  • a co-dimeric reaction is a reaction of N-methyl-N-bulacetamide represented by the following reaction formula (2) with 4-octyne. The yield of genamide in this reaction is 70%.
  • Genamide is a group of compounds useful in organic synthetic chemistry. For example, by using genamides as substrates for Diels-Alder reactions, it is possible to convert them into various unsaturated amidyl compounds having a ring structure, arlin derivatives, and the like. According to the production method of the present invention, this genamide can be easily produced by a very simple method of co-polymerization using N-Buramide and alkyne, which are cheaper starting materials than conventional ones. Monkey.
  • the chain codimerization reaction proceeds regioselectively. ⁇ , ⁇ and some E, ⁇ are generated. That is, according to the production method of the present invention, a high yield of genamide in which alkyne is introduced in a chain form on the side different from the amide nitrogen with respect to the carbon double bond of the vinyl group of ⁇ ⁇ -buluacetoamide. And can be manufactured with high selectivity.
  • R 2 independently represents a hydrogen atom, an alkyl group, or an aryl group.
  • R 1 and R 2 may be connected to each other to form a ring.
  • R 1 and R 2 represent a methylene group having 3 to 5 carbon atoms.
  • R 7 and R 8 each independently represents an alkyl group or an aryl group.
  • ruthenium complex in which the acid state of ruthenium is 0 is used as a catalyst.
  • the structure of the ruthenium complex catalyst is represented by the following chemical formula (2).
  • the neutral ligand consisting of a, ⁇ -unsaturated carboxylic acid ester or hydrocarbon power may be either a monodentate ligand, a bidentate ligand, or a tridentate ligand.
  • Neutral ligands include dimethyl fumarate (abbreviation dm & i), alkenes such as methyl acrylate, 1,5-cyclooctagen (abbreviation cod), 1,3,5-cyclootatatriene (abbreviation cot) ) And other aromatic compounds such as benzene.
  • dimethyl fumarate dimethyl fumarate (dmftn), 1,5-cyclooctadiene (cod), and 1,3,5-cyclootatatriene (cot) are preferable.
  • dimethyl fumarate is a monodentate ligand
  • 1,5-cyclooctagen is a bidentate ligand
  • 1,3,5-cyclootatriene is a tridentate ligand.
  • ruthenium complex catalyst examples include Ru (cod) (cot), Ru (cotXdmftn),
  • Ru (cotXdmftn) is particularly preferable.
  • N-Bulamide represented by the general formula (1) can be used in the same manner as in the method for producing enamide.
  • alkyne an alkyne represented by the following general formula (4) can be used.
  • R7 R 8 Formula (4)
  • R 7 and R 8 independently represent an alkyl group or an aryl group.
  • Examples of the alkyl group representing R 7 and R 8 include alkyl groups such as a methyl group and an ethyl group.
  • Examples of the aryl group representing R 7 and R 8 include a phenol group.
  • R 7 and R 8 are particularly preferably an alkyl group having 1 to 4 carbon atoms or a phenyl group.
  • 4-octyne, 5 decyne, 4,4 dimethyl-2-pentyne, 1-ferro-l-hexyne can be used as the above alkyne.
  • alkynes aliphatic alkynes having an unsaturated bond inside the long-chain alkyl group are preferred, such as when R 7 and R 8 are propyl groups or butyl groups.
  • R 7 and R 8 are propyl groups or butyl groups.
  • These aliphatic alkynes have good compatibility with the catalyst and improve the reaction yield.
  • 4-octyne is particularly preferable.
  • the reaction temperature is preferably in the range of 140 ° C to 170 ° C, particularly preferably in the range of 150 ° C to 170 ° C.
  • the reaction yield is remarkably improved.
  • the molar ratio of N-buramide to alkyne is preferably in the range of 1: 1 to 5: 1, more preferably in the range of 1: 1 to 3: 1, and particularly in the vicinity of 2: 1.
  • the reaction yield and selectivity are further improved.
  • ⁇ Ka ⁇ ruthenium complex catalyst to a preferred tool 1. 5 mole% to 5 mole% range in the range of 1 mol% to 5 mol 0/0 to N- Byuruamido is More preferred is around 2.5 mol%.
  • N-Methyl-N-Bulacetamide was used as N-Buramide
  • Ethyl acrylate was used as the alkene
  • N-Methyl-N-Bulacetoamide 1 09 mg (l. Immol) in an argon atmosphere
  • Ethyl acrylate 100mg (l.Ommol)
  • the obtained codimer was a colorless oily liquid.
  • the reaction yield of the codimer calculated from the GLC peak was 90%. No by-product of regioisomer was observed.
  • naphthalene as an internal standard substance, it was quantified by the internal standard method, and the yield was calculated.
  • Example 1 the co-dimerization reaction shown in the above reaction formula was carried out in the same manner as in Example 1 except that various reaction raw materials were changed. Since the molecular weights of the reaction raw materials are different, the added calorie weight is the same as that of Example 1 with different force added molar amounts. However, in Example 5, the molar amount of 2-norbornene added as alkene was set to 5. Ommol. Table 1 shows the reaction yield of the codimer calculated from the GLC peak. In the case of V and deviation, no by-product of regioisomer was observed.
  • a codimer was obtained in the same manner as in Example 9 except that the catalyst was replaced with Ru (cyclooctadienyl).
  • the reaction yield of the codimer calculated from the catalyst was 42%.
  • Codimer was prepared in the same manner as in Example 9 except that the catalyst was replaced with Ru (C H Xmethyl acrylate).
  • a codimer reaction was carried out in the same manner as in Example 1 except that the catalyst was not added, but the reaction did not proceed and no codimer was obtained.
  • a co-dimer reaction was carried out in the same manner as in Example 1 except that the catalyst was changed to Fe (CO).
  • a codimerization reaction was carried out in the same manner as in Example 10 except that the reaction temperature was changed from 160 ° C to 150 ° C and 170 ° C.
  • the reaction yield of the codimer calculated from the GLC peak was 45% at 150 ° C and 53% at 170 ° C. It was 56% at 160 ° C (Example 10). From this result, it can be seen that the reaction temperature is preferably in the range of 160 ° C to 170 ° C.
  • N-Methyl-N-Bulacetoamide is used as N-Buluamide, 4-Octin is used as the alkyne, and N-Methyl-N-Bulacetoamide 99 mg (1. Ommol), 4-Octin under an argon atmosphere 110mg (l. Ommol), ruthenium complex catalyst Ru (cot) (dmfm) 14.9mg (0.O3mmol), and DMA 3.Oml, equipped with three-way cock and magnetic rotor
  • the mixture was placed in a 20 ml glass reaction vessel made of Pyrex (registered trademark), and this mixture was heated and stirred for 3 hours while being heated to 170 ° C.
  • the reaction yield of the codimer calculated from the GLC peak was 10% at 130 ° C (ratio of ⁇ , ⁇ to ⁇ , ⁇ : 9.5: 1), and 21% at 140 ° C ( The ratio of ⁇ , ⁇ to ⁇ , ⁇ is 8.9: 1), 50% at 150 ° C (ratio of E, E to E, Z is 8. 1: 1), 50 to 160 ° C % (Ratio of E, E to E, Z) was 7.4: 1, and at 180 ° C, it was 42% (ratio of E, E to ⁇ , rod was 4.5: 1). In addition, at 170 ° C, it was 51% (ratio of rod, rod to rod, rod, 8.5: 1) (Example 15).
  • reaction temperature is preferably in the range of 150 ° C to 170 ° C.
  • Example 15 As shown in Table 3, Example 15 except that the molar ratio of N-butyramide (N-methyl-N-vinylacetamide) to alkyne (4-octyne) was changed from 1: 5 to 5: 1. Similarly, a co-dimerization reaction was carried out to obtain a co-dimer (Exemplary Compound 9).
  • the reaction yield of the codimer calculated from the GLC peak is 1% at a molar ratio of 1: 5 (ratio of ⁇ , ⁇ to ⁇ , ⁇ , ⁇ is 6.2: 1), and the molar ratio is 1 : 3 is 5% (ratio of ⁇ , ⁇ to ⁇ , ⁇ is 9.4: 1), and the molar ratio is 1: 2 to 16% (ratio of ⁇ , ⁇ to ⁇ , ⁇ is 8.8: 1) ), 30% at a molar ratio of 1: 1.5 (ratio of ⁇ , ⁇ to ⁇ , ⁇ , 8.6: 1), 53% at a molar ratio of 1.5: 1 ( ⁇ , ⁇ to ⁇ , ⁇
  • the ratio is 4.2: 1), the molar ratio is 2: 1 and 61% ( ⁇ , ⁇ to ⁇ , ⁇ , the ratio is 4.9: 1), and the molar ratio is 3: 1 to 50% ( ⁇ , ⁇ ).
  • the ratio of body to rod and rod was 4.7: 1), and the molar ratio was 5: 1, 49% (ratio of rod, rod to rod, rod was 5.6: 1). In addition, when the molar ratio was 1: 1, the ratio was 51% (the ratio of ⁇ , ⁇ to ⁇ , and ⁇ , 8.5: 1) (Example 15).
  • Example 26 Except for the change to force 0.01 mmol, 0.02 mmol, 0.05 mmol, 0.075 mmol, 0.1 mmol, a co-dimer reaction was carried out in the same manner as in Example 26 to obtain a co-dimer (Exemplary Compound (9 )). That is, as in Example 26, the molar ratio of N-buluamide to alkyne was 2: 1. It was. In Table 4, it was also shown mole 0/0 of N- Byuruamido ruthenium complex catalyst.
  • the reaction yield of the co-dimer calculated from the GLC peak is ⁇ vinyl / reamide ( ⁇ -methyl- ⁇ ⁇ buracetoamide) to 2 mmol and the catalyst amount is 0.
  • the ratio of E to E and Z is 9.7: 1), and the amount of catalyst is 0.02 mmol, 34% (the ratio of E, E to E, Z is 8.6: 1), and the amount of catalyst is 0 70% for O5mmol (ratio of E, E to E, Z forms is 3.5: 1), and 0% for O75mmol is 64% (ratio of E, E to E, Z forms is 3.1: 1), and the catalyst amount was 0.1 mmol, the ratio was 64% (the ratio of E, E form to E, Z form was 1.8: 1).
  • the amount of catalyst was 0. 0 3 mmol with respect to 2 mmol of N vinylenoamide, and the ratio was 61% (the ratio of E, E isomer to E, Z isomer was 4.9: 1) (Exa
  • the yield was gradually improved as the amount of the catalyst was increased, and the yield reached 70% when the amount of the catalyst was 0.025 mmol relative to 2 mmol of N bulamide (Example 31).
  • the amount of catalyst was further increased, the yield decreased.
  • the addition amount of ruthenium complex catalyst is 1 mol 0 / N to N-Buramide. It ⁇ 5 mol 0/0 preferably in the range of instrument 1.5 mole 0/0 more preferably tool that a 5 mole percent range 2.5 mol 0/0 before and after it is particularly preferred I understand.
  • a codimer (Exemplary Compound (10)) was obtained in the same manner as in Example 31, except that the alkyne was changed from 4-octyne to 5-decyne. That is, as in Example 31, the ruthenium complex catalyst The mol% with respect to N-Buramide was 2.5%. The obtained codimer was a yellow oily liquid. The reaction yield of the codimer calculated from the GLC peak was 45%. A chain-shaped genamide was selectively obtained. The ratio of ⁇ , ⁇ to ⁇ , ⁇ was 4.8: 1.
  • a codimer (Exemplified Compound (11)) was obtained in the same manner as in Example 31 except that the alkyne was changed from 4 octyne to 4,4 dimethyl 2-pentyne, which is an asymmetric alkyne, and the reaction time was 24 hours. .
  • the codimer obtained was a yellow oily liquid.
  • the isolation yield was 24%. Chained genamide was selectively obtained.
  • the ratio of rods and rods to rods and rods was over 40: 1, and the co-dimerization reaction proceeded stereoselectively.
  • N ((lE, 3Z) -3-Propylhepta-l, 3-dienyl) pyrrolidin-2-one (Exemplary compound (13), cocoon, rod)
  • a codimer (Exemplary Compound (14)) was obtained in the same manner as in Example 31, except that N-vinylamide was changed from N-methyl-N-vinylacetamide to N-vinylcaprolatatam.
  • the codimer obtained was a yellow oily liquid.
  • the reaction yield of the codimer calculated from the GLC peak was 42%. Chained genamide was selectively obtained.
  • the ratio of ⁇ , ⁇ to ⁇ , ⁇ was 3.2: 1.
  • N ((lE, 3E) -3-Propylhepta-l, 3-dienyl) azaperhydroepin-2-one (Exemplary compound (14), cocoon, rod)
  • a codimer reaction was carried out in the same manner as in Example 15 except that no catalyst was added. However, the reaction did not proceed and no codimer was obtained.
  • a co-dimer reaction was carried out in the same manner as in Example 15 except that the catalyst was changed to Fe (CO).
  • the reagents used in the above Examples and Comparative Examples were N-methyl-N-vinylacetamide (manufactured by Aldrich, purity 98%), 1-bul-2-pyrrolidone (manufactured by Aldrich, Purity 98%), N-Bielcaprolatatam (Avocado Research Chemicals, Ltd., purity 99%), Ethyl acrylate (Nacalai Testa, first grade), t-butyl acrylate (Aldrich, purity 98) ), Ethyl ketone (Aldrich, purity 97%), dimethyl maleate (Nacalai Testa, grade 1), 2-norbornene (Aldrich, purity 99%), ethylene (Sumitomo Seika, pure) ), N, N-dimethylacetamide (low moisture, manufactured by Nacalai Testa, first grade), 4-Otatin (manufactured by Aldrich, purity 99%), 5-decy
  • the Ru (cod) (cot) catalyst is a method described in K. Itoh, H. Nagashima, T. Oshima, N. Oshima and H. Nishiyama, J. Organomet. Chem., 1984, 272, 179. Was synthesized.
  • Ru (cotXdmftn) catalysts are available from T. Mitsudo, T. Suzuki, S.-W. Zhang, D. Imai, K. Fujita, T. Ma
  • Ru (cyclooctadienyl) catalyst is a P. Pertici, G
  • Ru (CO) catalyst is a commercial product (manufactured by Strem

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Abstract

La présente invention concerne de nouveaux procédés de production facile d’un énamide et d’un diénamide à partir de produits de départ moins coûteux que les produits de départs classiques sans produire de produit secondaire. Un N-vinylamide est mis à réagir avec un alcène en présence d'un catalyseur complexe de ruthénium contenant du ruthénium ayant une valence de 0 ou 2 de façon à produire un énamide. Un N-vinylamide est mis à réagir avec un alcyne en présence d'un catalyseur complexe de ruthénium contenant du ruthénium ayant une valence de 0 de façon à produire un diénamide.
PCT/JP2006/316892 2005-08-29 2006-08-28 Énamide et son procédé de production, et diénamide et son procédé de production Ceased WO2007026654A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008222621A (ja) * 2007-03-10 2008-09-25 Japan Science & Technology Agency β位に不斉点を有するカルボン酸の製造及び求核剤

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006056166A2 (fr) * 2004-11-24 2006-06-01 Studiengesellschaft Kohle Mbh Procede d'addition d'amides, de carbamides, de lactames et de carbamates a des alcynes

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
WO2006056166A2 (fr) * 2004-11-24 2006-06-01 Studiengesellschaft Kohle Mbh Procede d'addition d'amides, de carbamides, de lactames et de carbamates a des alcynes

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ZEZZA C.A. ET AL.: "Hydrolysis of cyclic 2-alkoxyiminium salts", HETEROCYCLES, vol. 34, no. 7, 1992, pages 1325 - 1342, XP003003802 *
ZIEGLER C.B. ET AL.: "Palladium-catalyzed vinylic substitution reactions of N-vinyl amides", JOURNAL OF ORGANIC CHEMISTRY, vol. 43, no. 15, 1978, pages 2949 - 2952, XP002134569 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008222621A (ja) * 2007-03-10 2008-09-25 Japan Science & Technology Agency β位に不斉点を有するカルボン酸の製造及び求核剤

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