JP2008544987A - Improved method for preparing insecticidal (disubstituted propenyl) phenylalkyl substituted heterocyclic rings - Google Patents

Abstract

［式中、Ｒ^３、Ｒ^４、Ｒ^５及びｘは、本明細書中で定義されているとおりである］の化合物を調製する段階に集中している。An improved method for preparing (disubstituted propenyl) phenylalkyl substituted heterocyclic rings has been described. This improved method is an important intermediate, namely formula (I)

Concentrates on the step of preparing the compound wherein R ³ , R ⁴ , R ⁵ and x are as defined herein.

Description

  The present invention belongs to the field of chemical methods. The present invention is more specifically an improved method for preparing (disubstituted propenyl) phenylalkyl substituted heterocyclic rings.

  (Disubstituted propenyl) phenylalkyl-substituted heterocyclic rings, for example

［式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４は、独立して、ハロゲン又はアルキルから選択され、Ｒ^５は、置換されていてもよい複素環式環基であり、ｘは、２、３、４、５又は６である］などは、有用な殺虫剤であり、米国特許第５，９２２，８８０号に記載されている（この特許の開示内容は、参照により本明細書に組み入れる）。これらの化合物を調製する方法の不利な点としては、収率が決して最適ではないこと、サイクル時間が決して最適ではないこと、及び、触媒の使用量が多いことなどがある。式（Ｉ）：

[Wherein R ¹ , R ² , R ³ and R ⁴ are independently selected from halogen or alkyl, R ⁵ is an optionally substituted heterocyclic ring group, and x is 2 , 3, 4, 5 or 6] are useful insecticides and are described in US Pat. No. 5,922,880, the disclosure of which is incorporated herein by reference. ). Disadvantages of the method of preparing these compounds are that the yield is never optimal, the cycle time is never optimal, and the amount of catalyst used is high. Formula (I):

［式中、Ｒ^３、Ｒ^４、Ｒ^５及びｘは、上記で定義されているとおりである］
の化合物は、米国特許第５，９２２，８８０号に記載されているように、（二置換プロペニル）フェニルアルキル置換複素環式環を調製する方法における重要な中間体である。

[Wherein R ³ , R ⁴ , R ⁵ and x are as defined above]
Is an important intermediate in the process of preparing (disubstituted propenyl) phenylalkyl substituted heterocyclic rings, as described in US Pat. No. 5,922,880.

  The present invention improves the process for preparing compounds of formula (I). As a result of the present invention, overall yield, cycle time and catalyst usage are improved for the preparation of (disubstituted propenyl) phenylalkyl substituted heterocyclic rings.

  Specifically, formula (I):

［式中、
Ｒ^３及びＲ^４は、独立して、ハロゲン又はアルキルから選択され；
Ｒ^５は、置換されていてもよい複素環式環基であり（但し、Ｒ^５は置換されていてもよいジヒドロベンゾフランではない）；及び、
ｘは、２、３、４、５又は６である］
の化合物が、
（ａ） 式（Ａ）：

[Where:
R ³ and R ⁴ are independently selected from halogen or alkyl;
R ⁵ is an optionally substituted heterocyclic ring group (provided that R ⁵ is not an optionally substituted dihydrobenzofuran); and
x is 2, 3, 4, 5 or 6]
The compound of
( A ) Formula ( A ):

［式中、Ｒ^５は、上記で定義されているとおりである］
の化合物を、塩基の存在下で、式（Ｂ）：

[Wherein R ⁵ is as defined above]
In the presence of a base of formula ( B ):

［式中、
Ｒ^６及びＲ^７は、独立して、ハロゲン、ヒドロキシル又は−ＯＳＯ_２Ｒ^８（ここで、Ｒ^８は、アルキル又はアリールである）から選択され；及び、
ｘは、２、３、４、５又は６である］
の化合物と反応させて、式（ＩＩ）：

[Where:
R ⁶ and R ⁷ are independently selected from halogen, hydroxyl or —OSO ₂ R ^8, where R ⁸ is alkyl or aryl; and
x is 2, 3, 4, 5 or 6]
Is reacted with a compound of formula (II):

［式中、Ｒ^５、Ｒ^７及びｘは、上記で定義されているとおりである］
の化合物を形成させること；及び、
（ｂ） 式（Ｃ）：

[Wherein R ⁵ , R ⁷ and x are as defined above]
Forming a compound of: and
(B) Formula ( C ):

［式中、Ｒ^３及びＲ^４は、上記で定義されているとおりである］
の化合物を、塩基の存在下で、式（ＩＩ）の化合物と反応させて、式（Ｉ）の化合物を形成させること；
を含む調製方法によって、優れた収率及び純度で調製され得るということが分かった。

[Wherein R ³ and R ⁴ are as defined above]
Reacting a compound of formula (I) with a compound of formula (II) in the presence of a base to form a compound of formula (I);
It was found that it can be prepared with excellent yield and purity by a preparation method comprising

The definition modifier “about” is definitively defined herein for certain preferred operating ranges, such as ranges for molar ratios with respect to reactants, ranges for the amount of material, and ranges for temperature. Used to indicate no. The implications will often be apparent to those skilled in the art. For example, if a temperature range of about 120 ° C. to about 135 ° C. is described for example for an organic chemical reaction, it may be expected to give another similar temperature (eg, 150 ° C., etc.). If there is a lack of guidance based on the experience of a person skilled in the art, lack of guidance based on context, and if more specific rules are not described below, the scope of “about” is 10% or less of the absolute value of the end point or 10% or less of the described range, whichever is smaller.

  As used herein, unless otherwise indicated, the substituent terms “alkyl”, “alkenyl”, “alkoxy” and “haloalkyl” may be used alone or in larger substructures. Even if used as part of the formula, at least one or two carbon atoms, preferably no more than 12 carbon atoms, more preferably no more than 10 carbon atoms, most preferably to be compatible with the substituent Includes straight or branched chains of up to 7 carbon atoms, where “alkenyl” has at least one carbon-carbon double bond. “Halogen”, “halide” or “halo” refers to fluorine, bromine, iodine or chlorine. The term “ambient temperature” means a temperature in the range of about 20 ° C. to about 30 ° C. Certain solvents, catalysts, etc. are known by their acronyms. Such includes the following acronyms: “DMAC” meaning N, N-dimethylacetamide, “DMF” meaning N, N-dimethylformamide, “THF” meaning tetrahydrofuran. The term “glymes” means a type of solvent composed of monoglyme, diglyme, triglyme, tetraglyme and polyglyme.

  The present invention relates to a compound of formula (I):

［式中、
Ｒ^３及びＲ^４は、独立して、ハロゲン又はアルキルから選択され；
Ｒ^５は、置換されていてもよい複素環式環基であり（但し、Ｒ^５は置換されていてもよいジヒドロベンゾフランではない）；及び、
ｘは、２、３、４、５又は６である］
の化合物を調製する方法に関し、ここで、該方法は、
（ａ） 式（Ａ）：

[Where:
R ³ and R ⁴ are independently selected from halogen or alkyl;
R ⁵ is an optionally substituted heterocyclic ring group (provided that R ⁵ is not an optionally substituted dihydrobenzofuran); and
x is 2, 3, 4, 5 or 6]
Wherein the method comprises the steps of:
( A ) Formula ( A ):

［式中、Ｒ^５は、上記で定義されているとおりである］
の化合物を、塩基の存在下で、式（Ｂ）：

[Wherein R ⁵ is as defined above]
In the presence of a base of formula ( B ):

［式中、
Ｒ^６及びＲ^７は、独立して、ハロゲン、ヒドロキシル又は−ＯＳＯ_２Ｒ^８（ここで、Ｒ^８は、アルキル又はアリールである）から選択され；及び、
ｘは、２、３、４、５又は６である］
の化合物と反応させて、式（ＩＩ）：

[Where:
R ⁶ and R ⁷ are independently selected from halogen, hydroxyl or —OSO ₂ R ^8, where R ⁸ is alkyl or aryl; and
x is 2, 3, 4, 5 or 6]
Is reacted with a compound of formula (II):

［式中、Ｒ^５、Ｒ^７及びｘは、上記で定義されているとおりである］
の化合物を形成させること；及び、
（ｂ） 式（Ｃ）：

[Wherein R ⁵ , R ⁷ and x are as defined above]
Forming a compound of: and
(B) Formula ( C ):

［式中、Ｒ^３及びＲ^４は、上記で定義されているとおりである］
の化合物を、塩基の存在下で、式（ＩＩ）の化合物と反応させて、式（Ｉ）の化合物を形成させること；
を含む。

[Wherein R ³ and R ⁴ are as defined above]
Reacting a compound of formula (I) with a compound of formula (II) in the presence of a base to form a compound of formula (I);
including.

  The reaction of step (a) can be carried out in the presence of a catalyst; it can be carried out at an elevated temperature. The catalyst can be polyethylene glycol, triethylamine, pyridine, a phase transfer catalyst, such as a quaternary ammonium salt or a quaternary phosphonium salt, or mixtures thereof. The catalyst can be present at a concentration of about 0.1% to about 15% by weight. The elevated temperature can range from 30 ° C to 120 ° C.

  The reaction of step (b) can be carried out in the presence of a solvent; it can be carried out in the presence of a catalyst; it can be carried out at an elevated temperature. The solvent is tetrahydrofuran, toluene, xylene, 1,2-dichloroethane, triethylamine, p-dioxane, N, N-dimethylacetamide, N, N-dimethylformamide, glymes, methyl isobutyl ketone, dimethyl sulfoxide or a mixture thereof. possible. The catalyst can be polyethylene glycol, potassium iodide, triethylamine, pyridine, a phase transfer catalyst, such as a quaternary ammonium salt or a quaternary phosphonium salt, or mixtures thereof. The catalyst can be present at a concentration of about 0.1% to about 20% by weight. The elevated temperature can range from 30 ° C to 70 ° C.

  Another embodiment of the present invention is a compound of formula (II):

［式中、
Ｒ^５は、置換されていてもよい複素環式環基であり（但し、Ｒ^５は置換されていてもよいジヒドロベンゾフランではない）；
Ｒ^７は、ハロゲン、ヒドロキシル又は−ＯＳＯ_２Ｒ^８（ここで、Ｒ^８は、アルキル又はアリールである）から選択され；及び、
ｘは、２、３、４、５又は６である］
の化合物である。

[Where:
R ⁵ is an optionally substituted heterocyclic ring group (provided that R ⁵ is not an optionally substituted dihydrobenzofuran);
R ⁷ is selected from halogen, hydroxyl or —OSO ₂ R ^8, where R ⁸ is alkyl or aryl; and
x is 2, 3, 4, 5 or 6]
It is a compound of this.

  The heterocyclic ring in the heterocyclic group which may be substituted is preferably isoxazole, thiazole, 1,3,4-thiadiazole, pyrrole, furan, thiophene, pyrazole, imidazole, 1,2,3. -Triazole, 1,2,4-triazole, 1,2,3,4-tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, 1,2,4-triazine, 1,3,5-triazine, indole, benzofuran, thia Naphthalene, indazole, benzimidazole, benzotriazole, benzoisoxazole, benzoxazole, benzothiazole, quinoline, isoquinoline, quinoxaline, quinazole, piperidine, piperazine, tetrahydrofuran, tetrahydropyran, pyrazoline, phthalimide, dioxane, dioxane It is selected from the group consisting of a run and benzodioxolane. The optional substituent of the optionally substituted heterocyclic ring group is preferably halogen, nitro, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl. Haloalkylsulfonyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, amino, dimethylamino, acetamide, acetyl, haloacetyl, formyl, carboxyl, methoxycarbonyl, cycloalkyl, (alkyl) aminocarbonyl, [di (alkyl) amino] carbonyl, Optionally substituted phenyl, optionally substituted benzyl, optionally substituted phenoxy, optionally substituted benzyloxy and optionally substituted pyr Aryloxy (where the optional substituents are halogen, alkyl, haloalkyl, it is selected from the group consisting of alkoxy or haloalkoxy) is selected from the group consisting of.

  The following examples illustrate how to prepare compounds of formula (I).

Example 1

(A) Base / catalyst / 30 ° C.-120 ° C./4-8 hours (b) Base / catalyst / solvent / 30 ° C.-70 ° C./6-12 hours

  In the first step (a) of Example 1, benzo [b] furan-7-ol (compound of formula (A)) is converted to 1,4-dihaloalkane (formula) at elevated temperature in the presence of a base and a catalyst. Compound of (B)), for example, reacted with 1,4-dihalobutane to give 1- (benzo [2,3-b] furan-7-yloxy) -4-haloalkane (compound of formula (II)), for example , 1- (benzo [2,3-b] furan-7-yloxy) -4-halobutane.

  In step (b) of Example 1, 2,6-dihalo-4- (phenylmethoxy) phenol (compound of formula (C)) is reacted with 1- (benzo) at elevated temperature in the presence of a base and a solvent and a catalyst. [2,3-b] furan-7-yloxy) -4-haloalkane (compound of formula (II)) such as 1- (benzo [2,3-b] furan-7-yloxy) -4-halobutane Reacting to 7- {4- [2,6-dihalo-4- (phenylmethoxy) phenoxy] alkoxy} benzo [b] furan (compound of formula (I)), for example 7- {4- [2, 6-Dihalo-4- (phenylmethoxy) phenoxy] butoxy} benzo [b] furan is formed.

Example 2

(A) Base / catalyst / 30 ° C.-120 ° C./4-8 hours (b) Base / catalyst / solvent / 30 ° C.-70 ° C./6-12 hours

  In the first step (a) of Example 2, a substituted pyridin-2-ol (compound of formula (A)), for example 5- (trifluoromethyl) pyridin-2-ol, is heated at elevated temperature to the base and catalyst. In the presence of 1,4-dihaloalkane (compound of formula (B)), for example 1,4-dihalobutane, reacted with 1- (substituted pyridin-2-yloxy) -4-haloalkane (formula (II) Compound), for example 1-((5-trifluoromethyl) pyridin-2-yloxy) -4-halobutane.

  In step (b) of Example 2, 2,6-dihalo-4- (phenylmethoxy) phenol (compound of formula (C)) is treated with 1- (substituted) at elevated temperature in the presence of a base and a solvent and a catalyst. Pyridin-2-yloxy) -4-haloalkane (compound of formula (II)), for example 1-((5-trifluoromethyl) pyridin-2-yloxy) -4-halobutane, is reacted with 2- {4 -[2,6-dihalo-4- (phenylmethoxy) phenoxy] alkoxy} substituted pyridine pyridine (compound of formula (I)), for example 2- {4- [2,6-dihalo-4- (phenylmethoxy) Phenoxy] butoxy} -5- (trifluoromethyl) pyridine is formed.

  Although the invention has been described with an emphasis on preferred embodiments, variations on the preferred embodiments described above can be used and the methods described herein differ from those specifically described herein. It will be apparent to those skilled in the art that the invention may be practiced. Accordingly, this invention includes all modifications encompassed within the spirit and scope as defined by the appended claims.

Claims (10)

Formula (I):

[Where:
R ³ and R ⁴ are independently selected from halogen or alkyl;
R ⁵ is an optionally substituted heterocyclic ring group (provided that R ⁵ is not an optionally substituted dihydrobenzofuran); and
x is 2, 3, 4, 5 or 6]
A process for preparing a compound comprising:
( A ) Formula ( A ):

[Wherein R ⁵ is as defined above]
In the presence of a base of formula ( B ):

[Where:
R ⁶ and R ⁷ are independently selected from halogen, hydroxyl or —OSO ₂ R ^8, where R ⁸ is alkyl or aryl; and
x is 2, 3, 4, 5 or 6]
Is reacted with a compound of formula (II):

[Wherein R ⁵ , R ⁷ and x are as defined above]
Forming a compound of: and
(B) Formula ( C ):

[Wherein R ³ and R ⁴ are as defined above]
Reacting a compound of formula (I) with a compound of formula (II) in the presence of a base to form a compound of formula (I);
Said method.   The process of claim 1, wherein the reaction of step (a) is carried out in the presence of a catalyst.   The process of claim 1, wherein the reaction of step (a) is carried out at an elevated temperature.   The process of claim 1, wherein the reaction of step (b) is carried out in the presence of a solvent.   The process of claim 1, wherein the reaction of step (b) is carried out in the presence of a catalyst.   The process of claim 1, wherein the reaction of step (b) is carried out at an elevated temperature.   The heterocyclic ring in the optionally substituted heterocyclic ring group is isoxazole, thiazole, 1,3,4-thiadiazole, pyrrole, furan, thiophene, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,3,4-tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, 1,2,4-triazine, 1,3,5-triazine, indole, benzofuran, thiaphthalene, indazole , Benzimidazole, benzotriazole, benzisoxazole, benzoxazole, benzothiazole, quinoline, isoquinoline, quinoxaline, quinazole, piperidine, piperazine, tetrahydrofuran, tetrahydropyran, pyrazoline, phthalimide, dioxane, dioxolane and Selected from a group consisting of Zojiokisoran The method of claim 1.   Optional substituents on the optionally substituted heterocyclic ring group are halogen, nitro, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, Alkenyl, haloalkenyl, alkynyl, haloalkynyl, amino, dimethylamino, acetamide, acetyl, haloacetyl, formyl, carboxyl, methoxycarbonyl, cycloalkyl, (alkyl) aminocarbonyl, [di (alkyl) amino] carbonyl, substituted Optionally substituted benzyl, optionally substituted benzyl, optionally substituted phenoxy, optionally substituted benzyloxy and optionally substituted pyridyloxy (here , Optional substituents include halogen, alkyl, haloalkyl, is selected from the group consisting of selected from the group consisting of alkoxy or haloalkoxy), The method of claim 7. Formula (II):

[Where:
R ⁵ is an optionally substituted heterocyclic ring group (wherein the heterocyclic ring within the optionally substituted heterocyclic ring group is isoxazole, thiazole, 1, 3, 4-thiadiazole, pyrrole, furan, thiophene, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,3,4-tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, 1, 2,4-triazine, 1,3,5-triazine, indole, benzofuran, thiaphthalene, indazole, benzimidazole, benzotriazole, benzisoxazole, benzoxazole, benzothiazole, quinoline, isoquinoline, quinoxaline, quinazole, piperidine, piperazine , Tetrahydrofuran, tetrahydropyran , Selected from the group consisting of pyrazoline, phthalimide, dioxane, dioxolane and benzodioxolane);
R ⁷ is selected from halogen, hydroxyl or —OSO ₂ R ^8, where R ⁸ is alkyl or aryl; and
x is 2, 3, 4, 5 or 6]
Compound.   Optional substituents on the optionally substituted heterocyclic ring group are halogen, nitro, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, Alkenyl, haloalkenyl, alkynyl, haloalkynyl, amino, dimethylamino, acetamide, acetyl, haloacetyl, formyl, carboxyl, methoxycarbonyl, cycloalkyl, (alkyl) aminocarbonyl, [di (alkyl) amino] carbonyl, substituted Optionally substituted benzyl, optionally substituted benzyl, optionally substituted phenoxy, optionally substituted benzyloxy and optionally substituted pyridyloxy (here , Optional substituents include halogen, alkyl, haloalkyl, is selected from the group consisting of selected from the group consisting of alkoxy or haloalkoxy), compound of Claim 9.