JP2010013431A - Method for producing (z,z)-1,4-dihalo-1,3-butadiene compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a (Z,Z)-1,4-dihalo-1,3-butadiene compound and a method for easily and efficiently producing the compound. <P>SOLUTION: The method for producing a (Z,Z)-1,4-dihalo-1,3-butadiene compound expressed by general formula (3) comprises the reaction of a terminal acetylene compound expressed by general formula (1) with a trihaloacetic acid halide expressed by general formula (2) in the presence of a rhodium compound catalyst. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a method for producing a (Z, Z) -1,4-dihalo-1,3-butadiene compound.

  1,3-diene compounds are synthesized by a wide variety of reactions such as Wittig reaction, Tube reaction, Hoffman elimination and vinyl compound coupling reactions, and are used as raw materials for synthesizing heteroaromatic rings such as pyrrole useful as physiologically active substances. In addition, since it undergoes many conversion reactions such as Diels-Alder reaction, it is a very useful group of compounds (Non-Patent Document 1), and a huge number of compounds are known as this category of compounds.

Of these compounds, only limited compounds are known for (Z, Z) -1,4-dihalo-1,3-butadiene compounds in which both the 1- and 4-position carbons of the butadiene moiety are substituted with halogens. Although not used as light emitting materials such as silole and phosphole (Non-Patent Documents 2 and 3), as a monomer (Non-Patent Document 4) in polymer synthesis such as conjugated polyene, and cyclopentadienone derivative synthesis (Non-Patent Documents) 5), examples of use in polysubstituted pyridine synthesis (Non-Patent Document 6), furan derivative synthesis (Non-Patent Document 7), and benzene derivative synthesis (Non-Patent Document 8) have been reported. However, the synthesis of the (Z, Z) -1,4-dihalo-1,3-butadiene compound involves (i) a method of coupling a terminal alkyne in the presence of a palladium salt and a copper salt (Non-Patent Document 9), or (Ii) A method of quenching with a halogen alone after forming a metallacycle using two-cycle alkyne molecules using a metal reagent such as Zr or Ti (Non-patent Document 10). In the method, a large amount of copper salt is required, and the reaction system becomes heterogeneous, which makes it difficult for the reaction to proceed smoothly. The method (ii) requires a stoichiometric amount of a metal-containing reagent that requires a detour in preparation, and the yield is generally not high.
Synthesis, 1993, p. 349 Journal of the American Chemical Society, 2007, 129, p. 3094 European Journal of Inorganic Chemistry, 2005, p. 637 Liebigs Annalen, 1995, p. 223 Journal of the American Chemical Society, 2005, 127, p. 8024 Journal of the American Chemical Society, 2002, 124, p. 6238 Journal of the Chemical Society, Chemical Communication, 1990, p. 1127 Journal of the American Chemical Society, 2003, 125, p. 6884 The Journal of Organic Chemistry, 2004, 69, p. 8125 The Journal of Organic Chemistry, 1998, 63, p. 10060

  An object of the present invention is to provide a simple and efficient method for producing a (Z, Z) -1,4-dihalo-1,3-butadiene compound.

  The inventors have found that a 1,4-dichloro-3-buten-2-one compound can be obtained by reacting a terminal acetylene compound with an alpha chlorocarboxylic acid chloride having a chlorine atom at the alpha position, An application was filed as a 4-dichloro-3-buten-2-one compound and a production method thereof (Japanese Patent Application No. 2007-054811). As a result of further diligent research on this method, when tritrihaloacetic acid halides in which the substituent at the carbon at the alpha position is all a chlorine atom are reacted, the chlorination dimerization reaction of alkyne proceeds in a completely different manner from the previous invention. As a result, the present invention has been completed based on this unexpected result.

  That is, the present invention relates to the general formula (1)

（式中、Ｒは、水素原子、炭素数１４以下の脂肪族飽和炭化水素基、炭素数１４以下の脂肪族不飽和炭化水素基、炭素数１４以下の芳香族炭化水素基、炭素数１５以下のアラルキル基、フェロセニル基、シリル基を表し、Ｒが芳香族炭化水素基又はアラルキル基で構成される場合の芳香族炭化水素基又はアラルキル基中の芳香環は炭素数１２以下の複素芳香環であっても良い。また、Ｒは官能基によって置換されていても良い。）で表される末端アセチレン化合物と、一般式（２）

(In the formula, R is a hydrogen atom, an aliphatic saturated hydrocarbon group having 14 or less carbon atoms, an aliphatic unsaturated hydrocarbon group having 14 or less carbon atoms, an aromatic hydrocarbon group having 14 or less carbon atoms, or 15 or less carbon atoms. An aralkyl group, a ferrocenyl group, and a silyl group, and when R is an aromatic hydrocarbon group or an aralkyl group, the aromatic ring in the aromatic hydrocarbon group or aralkyl group is a heteroaromatic ring having 12 or less carbon atoms. And R may be substituted with a functional group), and a terminal acetylene compound represented by the general formula (2):

（式中、Ｘは塩素原子又は臭素原子を表す。）で表されるトリハロ酢酸ハライドとを、ロジウム化合物触媒の存在下に反応させることを特徴とする、一般式（３）

(Wherein X represents a chlorine atom or a bromine atom), and a trihaloacetic acid halide represented by the general formula (3) is reacted in the presence of a rhodium compound catalyst.

（式中、Ｒ及びＸは、前記と同じ意味を表す。）で表される（Ｚ，Ｚ）−１，４−ジハロ−１，３−ブタジエン化合物の製造方法を提供する

(In the formula, R and X represent the same meaning as described above.) Provided is a method for producing a (Z, Z) -1,4-dihalo-1,3-butadiene compound represented by

  Each group shown in this specification is specifically as follows.

  Examples of the aliphatic saturated hydrocarbon group having 14 or less carbon atoms include n-tetradecyl group, n-decyl group, n-decyl group, n-nonyl group, n-octyl group, ethylhexyl group, n-hexyl group, cyclohexyl group, n-pentyl group, isopentyl group, n-butyl group, sec-butyl group, isobutyl group, n-propyl group, isopropyl group, ethyl group, methyl group, cyclohexyl group, decahydronaphthyl group, etc. A cyclic aliphatic saturated hydrocarbon group can be exemplified.

  Examples of the aliphatic unsaturated hydrocarbon group having 14 or less carbon atoms include vinyl group, isopropenyl group, 1-propenyl group, allyl group, 1-buten-1-yl group, 2-buten-1-yl group, 3- Buten-1-yl group, 3-buten-2-yl group, 2,2-dimethylvinyl group, 1-penten-1-yl group, 2-penten-1-yl group, 3-penten-1-yl group 3-penten-2-yl group, 4-penten-1-yl group, 4-penten-2-yl group, 4-penten-3-yl group, 4-penten-4-yl group, 1,2- Dimethyl-1-buten-1-yl group, 1-octen-1-yl group, 1-decene-1-yl group, 1-tetradecene-1-yl group, 13-tetradecene-1-yl group, 1-cyclohexene -1-yl group, 1-cyclohexen-3-yl group, 1-cyclooct Down-1-yl group, 1-methyl-1-linear, such as cyclohexen-2-yl group, can be exemplified branched or cyclic aliphatic unsaturated hydrocarbon group.

  Examples of the aromatic hydrocarbon group having 14 or less carbon atoms include a phenyl group, a paratolyl group, a metatolyl group, a paracumyl group, an alpha naphthyl group, a beta naphthyl group, a beta anthryl group, an orthobiphenyl group, a metabiphenyl group, and a parabiphenyl group. The aromatic hydrocarbon group can be illustrated.

  Examples of the aralkyl group having 15 or less carbon atoms include aralkyl groups such as a benzyl group, an alpha or beta phenylethyl group, an alpha or beta naphthylmethyl group, and a beta anthrylmethyl group.

  Examples of silyl groups include triorganosilyl groups substituted with three types of aromatic or aliphatic saturated hydrocarbon groups having 6 or less carbon atoms, and examples include trimethylsilyl groups, t-butyldimethylsilyl groups, and phenyldimethylsilyl groups. I can do it.

  Examples of the heteroaromatic ring having 12 or less carbon atoms include thiophene ring, furan ring, pyrrole ring, pyran ring, pyridine ring, pyrazine ring, quinoline ring, isoquinoline ring, quinoxaline ring, benzofuran ring, pyrrole ring, indole ring, carbazole ring, etc. Can be illustrated.

  When R is substituted with a functional group, the functional group includes an ether group, an ester group, a carbamoyl group, an acyl group, an amino group, a sulfide group, a silyl group, a siloxy group, a cyano group, and a halogen atom. It can be illustrated. As an ether group, ether groups, such as a methoxy group, an ethoxy group, a phenoxy group, can be illustrated. Examples of the ester group include ester groups such as a carbomethoxy group and a carbophenoxy group. Examples of the carbamoyl group include an unsubstituted carbamoyl group, an N-methylcarbamoyl group, an N, N-dimethylcarbamoyl group, and an N-phenylcarbamoyl group. Examples of the acyl group include an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a benzoyl group, a paratoluyl group, an alpha or beta naphthoyl group, and the like. Examples of the amino group include a dimethylamino group, a diethylamino group, and a pyrrolyl group. Examples of the sulfide group include a methylthio group, an ethylthio group, and a phenylthio group. Examples of the silyl group include a trimethylsilyl group, a t-butyldimethylsilyl group, and a phenyldimethylsilyl group. Examples of the siloxy group include trimethylsiloxy group, t-butyldimethylsiloxy group, phenyldimethylsiloxy group and the like. Examples of halogen atoms include fluorine and chlorine.

  Hereinafter, the production method of the present invention will be described in detail.

    General formula (3)

（式中、Ｒ及びＸは、前記と同じ意味を表す。）で表される（Ｚ，Ｚ）−１，４−ジハロ−１，３−ブタジエン化合物は、一般式（１）

(Wherein R and X represent the same meaning as described above), the (Z, Z) -1,4-dihalo-1,3-butadiene compound represented by the general formula (1)

（式中、Ｒは、前記と同じ意味を表す。）で表される末端アセチレン化合物と、一般式（２）

(Wherein R represents the same meaning as described above), and a terminal acetylene compound represented by the general formula (2)

（式中、Ｘは塩素原子又は臭素原子を表す。）で表されるトリハロ酢酸ハライドとを、ロジウム化合物触媒の存在下に反応させることにより製造される。

(Wherein X represents a chlorine atom or a bromine atom) and is produced by reacting with a trihaloacetic acid halide represented by the presence of a rhodium compound catalyst.

    Although there is no restriction | limiting in the molar ratio of the trihaloacetic acid halide represented by General formula (2) with respect to the terminal acetylene compound represented by General formula (1), Generally, it selects from the range of 0.3-2.0. It is.

The reaction of the present invention proceeds at a preferred rate in the presence of a transition metal compound catalyst, particularly a rhodium compound catalyst. As the rhodium compound, compounds having various structures can be used, but a preferable one is a so-called low-valent rhodium complex. Specifically, RhCl (PPh ₃ ) ₃ , RhCl (CO) (PPh ₃ ) ₂ , RhCl (CO) (AsPh ₃ ) ₂ , RhCl (CO) [P (o-Tol) ₃ ] ₂ , RhCl (CO ) (PPhMe ₂ ) ₂ , RhCl (CO) (PMe ₃ ) ₂ , RhCl (CO) [Ph ₂ P (CH ₂ ) ₄ PPh ₂ ], RhCl (CO) (AsPh ₃ ) ₂ , RhCl (CO) (dpaf ), RhCl (CO) (dppf), RhCl (cod) (PPh ₃ ), RhCl (cod) (PPhMe ₂ ), RhCl (cod) (PMe ₃ ), RhCl (Cod) (AsPh ₃ ), Rh (acac) _{(CO) (PPh 3),} Rh (acac) (CO) (AsPh 3), Rh (acac) (CO) [P (Mes) 3], Rh (acac) (C _{) [P (1-Naph)} 3], RhCl (CO) (o- diphenylphosphinophenyl oxazoline), RhCl (CO) [1,2- ethylenebis _{(oxazoline)], [RhCl (CO)} 2] 2, _{[RhCl (cod)] 2,} [RhCl (CH 2 = CH 2) 2] 2, Rh (acac) (cod), Rh (acac) (CO) 2 and the like. In the description of the above specific examples, Tol represents a tolyl group, dpaf represents 1,1′-bis (diphenylarsino) ferrocene, dppf represents 1,1′-bis (diphenylphosphino) ferrocene, cod Represents cyclooctadiene, acac represents acetylacetonate, Mes represents a 2,4,6-trimethylphenyl group, and Naph represents a naphthyl group. Among these, a rhodium complex having a sterically bulky trivalent phosphorus compound such as P (o-Tol) ₃ or P (Mes) ₃ as a ligand is particularly preferably used.

Further, a method of adding a ligand to a rhodium compound in a reaction system to generate an active species and using it as a catalyst as it is is also included in a preferred embodiment of the present invention. The rhodium compounds in this case include [RhCl (CO) ₂ ] ₂ , [RhCl (cod)] ₂ , [RhCl (1,5-hexadiene)] ₂ , [RhCl (CH ₂ ═CH ₂ ) ₂ ] ₂ , Rh (acac) (cod), Rh (acac) (CO) _{2 and the} like are exemplified. In addition, as a ligand, a ligand having a phosphine structure, a phosphite structure, an arsine structure, or an imine structure, or a ligand that includes any one of the phosphine structure, phosphite structure, arsine structure, and imine structure at the same time. Quantifiers are included. Further, two or more kinds of ligands having a phosphine structure, a phosphite structure, an arsine structure, or an imine structure may be mixed and used. Specifically, triphenylphosphine, tri (o-tolyl) phosphine, tri (1-naphthyl) phosphine, trimesitylphosphine, trimethylphosphine, diphenylmethylphosphine, dicyclohexyl (p-biphenyl) phosphine, 1,1-bis ( Diphenylphosphino) ferrocene, 9,9-dimethyl-4,5-bis (diphenylphosphino) xanthene, triphenylphosphite, triphenylarsine, 1,1-bis (diphenylarsino) ferrocene, [o- (diphenylphos Phino) phenyl] oxazoline, 1,2-ethylenebis (oxazoline) and the like, but sterically bulky phosphines such as tri (o-tolyl) phosphine, tri (1-naphthyl) phosphine, and trimesitylphosphine Phosphorus compound of structure Exhibit particularly preferred effects. The addition amount of the ligand with respect to the rhodium complex is in the range of 1: 0.5 to 1:10, preferably 1: 1 to 1: in terms of the molar ratio of the coordination element in the ligand to the rhodium atom in the rhodium compound. A range of 2 is selected.

  The amount of these rhodium compounds used may be a so-called catalytic amount, and 20 mol% or less is sufficient with respect to the acetylene compound.

  The reaction of the present invention proceeds even in the presence of oxygen such as air. However, since the reaction intermediate is somewhat sensitive to oxygen, it is preferably carried out in an inert gas atmosphere such as nitrogen, argon or methane. The reaction of the present invention does not particularly require the use of a solvent, but can also be carried out in a solvent if necessary. Solvents include hydrocarbon solvents such as hexane, cyclohexane, octane, benzene, toluene, and ethylbenzene; halogenated hydrocarbon solvents such as chloroform, tetrachloroethane, and chlorobenzene; diethyl ether, diisopropyl ether, dimethoxyethane, dibutyl ether, and anisole. , Cyclopentyl methyl ether, tert-butyl methyl ether, diphenyl ether, ether solvents such as 1,4-dioxane; ester solvents such as ethyl acetate and butyl acetate; various solvents such as ketone solvents such as acetone, methyl ethyl ketone, and acetophenone Can be used. Moreover, these are used individually or in mixture of 2 or more types.

  The reaction of the present invention can be generally carried out in the temperature range of 0 ° C. to 200 ° C., but is preferably selected from the range of 40 to 160 ° C.

  The reaction time varies depending on the reaction temperature, whether or not a solvent is used, the type of acetylene compound used, and the like, but is usually 0.1 to 48 hours.

  Separation and purification of the purified product from the reaction mixture can be easily achieved by a commonly performed method such as various chromatography, distillation or recrystallization.

  The (Z, Z) -1,4-dihalo-1,3-butadiene compound represented by the general formula (3) of the present invention is useful as a synthetic raw material for conjugated polymers, heterocyclic compounds, pharmaceuticals, agricultural chemicals and the like. . Moreover, according to the production method of the present invention, it can be produced easily and in high yield from easily available terminal acetylene compounds and trihaloacetic acid halides, and their separation and purification are also easy. Therefore, it is very useful industrially.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

Example 1
1-octyne (1 mmol), trichloroacetyl chloride (1 mmol), [RhCl (CO) ₂ ] ₂ (0.05 mmol per rhodium atom) as a rhodium compound, P as a ligand in a reaction vessel having an internal volume of 5 mL under a nitrogen atmosphere (Mes) ₃ (0.1 mmol) and chlorobenzene (1 mL) were added, and the mixture was heated and stirred at 130 ° C. for 3 hours. After cooling to room temperature, 1,1,2,2-tetrachloroethane (24.3 mg) was added as an internal standard substance, and as a result of analysis by ¹ H NMR spectrum, (Z, Z) -7,10-dichloro-7, It was found that 9-hexadecaene was produced in a yield of 91%. The reaction solution was concentrated under reduced pressure, and purified by preparative thin layer chromatography using hexane to obtain (Z, Z) -7,10-dichloro-7,9-hexadecaene.

Examples 2-17
The reaction time was 12 hours, the rhodium compound, the ligand, the solvent, or the reaction temperature was varied, and the reaction was performed in the same manner as in Example 1 and analyzed by ¹ H NMR spectrum. The yields of (Z, Z) -7,10-dichloro-7,9-hexadecaene are summarized in Table 1.

Example 18
In a nitrogen atmosphere, in a reaction vessel having an internal volume of 5 mL, 1-decyne (1 mmol), tribromoacetyl bromide (1 mmol), [RhCl (CO) ₂ ] ₂ (0.05 mmol per rhodium atom) as a rhodium compound, P (Mes) ₃ (0.1 mmol) as a ligand and n-tetradecane (20.6 mg) as an internal standard for gas chromatography analysis were added to chlorobenzene (1 mL), and the mixture was heated and stirred at 90 ° C. for 3 hours. As a result of gas chromatography analysis, it was found that (Z, Z) -9,12-dibromo-9,11-eicosadiene was produced in a yield of 43%. The reaction solution was concentrated under reduced pressure, and (Z, Z) -9,12-dibromo-9,11-icosadien was obtained by repeated separation and purification by preparative thin layer chromatography using hexane as a developing solution.

Examples 19-32
Table 2 summarizes the results of the same reactions as in Example 1 using various terminal acetylene compounds instead of 1-octyne.

Claims (5)

General formula (1)

(In the formula, R is a hydrogen atom, an aliphatic saturated hydrocarbon group having 14 or less carbon atoms, an aliphatic unsaturated hydrocarbon group having 14 or less carbon atoms, an aromatic hydrocarbon group having 14 or less carbon atoms, or 15 or less carbon atoms. An aralkyl group, a ferrocenyl group, and a silyl group, and when R is an aromatic hydrocarbon group or an aralkyl group, the aromatic ring in the aromatic hydrocarbon group or aralkyl group is a heteroaromatic ring having 12 or less carbon atoms. And R may be substituted with a functional group), and a terminal acetylene compound represented by the general formula (2):

(Wherein X represents a chlorine atom or a bromine atom), and a trihaloacetic acid halide represented by the general formula (3) is reacted in the presence of a rhodium compound catalyst.

(In the formula, R and X represent the same meaning as described above.) A method for producing a (Z, Z) -1,4-dihalo-1,3-butadiene compound represented by:   The process according to claim 1, wherein a rhodium compound is used as a catalyst.   The method according to claim 1, wherein a rhodium compound having a trivalent phosphorus compound as a ligand is used as a catalyst.   The process according to claim 1, wherein a ligand is added to the rhodium compound in the reaction system to generate active species and used as a catalyst as it is.   The process according to claim 1, wherein in the reaction system, a trivalent phosphorus compound is added to the rhodium compound as a ligand to generate active species and used as a catalyst as it is.