JP2006083066A - 5,5,5-trifluoro-3-penten-1-ynes and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an industrial method for producing 5,5,5-trifluoro-3-penten-1-ynes useful as a synthetic intermediate for functional materials such as medicines, agrochemicals or fluorine-containing polymers and to provide the several kinds of 5,5,5-trifluoro-3-penten-1-ynes which are new compounds. <P>SOLUTION: 1-Chloro-2-trifluromethyl-ethylenes are reacted with various terminal acetylenes in the presence of a palladium catalyst and a basic substance. Organic amines such as piperidine or diethylamine are especially preferable as the base to be used. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention is 5,5,5-trifluoro-3-penten-1-yne, which is a substituted or terminal acetylene, useful as a raw material or synthetic intermediate for the production of functional materials such as pharmaceuticals, agricultural chemicals and fluoropolymers. Class and its manufacturing method.

  Since fluorine-containing compounds can be expected to have various physiological activities, research and development as pharmaceuticals and agricultural chemicals have been made (Non-patent Document 1). Further, from a synthetic chemical viewpoint, the enyne skeleton having both an olefin moiety and an acetylene moiety is highly functionalized and can be converted in various ways. Therefore, the fluorine-containing enyne compound is an important intermediate for fluorine-containing fine chemical derivatives as a raw material for producing functional materials such as pharmaceuticals, agricultural chemicals, and fluorine-containing polymers, or as a synthetic intermediate.

  Enyne compounds include many antibiotics such as Siccayne and substances exhibiting antitumor properties, and are useful as pharmaceuticals such as antibiotics, pesticides such as fungicides and plant growth regulators (Non-patent Document 2).

  In particular, fluorine-containing enynes are widely used as monomers of fluorine-containing functional polymers such as insulating materials, electrostatic development toners, and water- and oil-repellent polymers, and are generally known as extremely useful compound groups. (Non-patent Document 3).

  Conventionally, as a method for producing 5,5,5-trifluoro-3-penten-1-ynes, which are substituted acetylenes containing fluorine, 1,1-difluoro generated from 1,1-difluoroethylene and butyllithium is used. By converting ketone lithium to a 1,1-difluoroallyl alcohol compound and then fluorinating with DAST (diethylaminosulfur trifluoride) under dehydrating conditions in two steps, A method for obtaining a substituted-5,5,5-trifluoro-3-penten-1-yne compound (Non-Patent Document 4) is known. Further, 1-substituted-5,5,5-trifluoro-3-penten-1-yne compound is obtained by reacting trifluoromethyl iodide with terminal acetylene in the presence of a palladium catalyst and a basic substance. A method (Patent Document 1) is known. Furthermore, 1,2,3,3,3-pentafluoro-1-iodinated-propene was reacted with terminal acetylene in the presence of a palladium catalyst and a basic substance to thereby replace the 1,5-substituted 5,5 A method of obtaining a 5-trifluoro-3-penten-1-yne compound (Non-Patent Document 5) is known.

On the other hand, as a method for synthesizing alkyl-substituted-3-penten-1-ynes containing no fluorine, a method of reacting alkyl-substituted vinyl chlorides and terminal acetylenes in the presence of a palladium catalyst and a basic substance (non- Patent document 6) is known.
Japanese Examined Patent Publication No. 7-20893 Introduction to Fluorine Chemistry Sankyo Publishing (2004) Journal of Synthetic Organic Chemistry, 1992, Vol. 50, No. 11, p. 940-952 Organofluorine Chemistry (II) Gihodo (1973) Journal of Fluorine Chemistry, 62, 183-189 1993 (UK) Journal of Fluorine Chemistry, 53, 307-326 1991 (UK) Journal of Organometallic Chemistry, 624, 114-123 2001 (Netherlands)

  The above method for producing 5,5,5-trifluoro-3-penten-1-ynes is suitable for small-scale implementation, but is difficult to employ industrially.

  In the method disclosed in Non-Patent Document 4, the 1,1-difluorovinyllithium reagent needs to be handled at a low temperature of about −100 ° C., and the obtained 1,1-difluoroallyl alcohol compound is very inefficient. Since it decomposes stably and easily, it must be processed quickly and the reaction operation is complicated. Furthermore, it is necessary to use DAST (diethylaminosulfur trifluoride) as a reagent, but this reagent is very expensive.

  In the method disclosed in Patent Document 1, expensive trifluoromethyl iodide is used as a raw material, and it is difficult to dispose of an iodide salt by-produced after the reaction. Furthermore, since the product obtained is a mixture of cis-trans isomers, the production efficiency is poor to selectively obtain one isomer, and it is difficult to employ industrially.

  In the method shown in Non-Patent Document 5, 1-iodinated-3,3,3-trifluoropropene as a raw material is expensive, and further, it is difficult to dispose of an iodide salt produced as a by-product after the reaction. It was difficult to implement this method industrially.

  As described above, the production of 5,5,5-trifluoro-3-penten-1-ynes is quite difficult, and it has been desired to establish an industrial production method that can be carried out efficiently and in the future.

  The inventors of the present invention have made extensive studies in order to solve the above problems. As a result, 1-chloro-2-trifluoromethyl-ethylenes represented by the formula [1]

を、式［２］で表される末端アセチレン類

Terminal acetylenes represented by the formula [2]

と、パラジウム触媒と塩基性物質の存在下で反応させることによって、式［３］で表わされる、５，５，５−トリフルオロ−３−ペンテン−１−イン類

And 5,5,5-trifluoro-3-penten-1-ynes represented by the formula [3] by reacting with a palladium catalyst and a basic substance

を高収率で得られることを見出し、上記課題が解決することを見出した。（式［１］〜［３］中、Ｒ¹は水素原子、フッ素原子またはトリフルオロメチル基を表し、Ｒ²は水素原子、フッ素原子、または塩素原子を表す。Ｒ³は、水素原子、フェニル基（ここでフェニル基の水素原子の一部または全てはハロゲン（フッ素、塩素、臭素、ヨウ素）、アミノ基もしくはヒドロキシル基で置換されていても良い）、炭素数１〜６の直鎖、分岐鎖もしくは環状のアルキル基（ここでアルキル基の水素原子の一部または全てはハロゲン（フッ素、塩素、臭素、ヨウ素）、アミノ基もしくはヒドロキシル基で置換されていても良い）、炭素数１〜６の直鎖、分岐鎖もしくはアリール基（ここでアリール基の水素原子の一部または全てはハロゲン（フッ素、塩素、臭素、ヨウ素）、アミノ基もしくはヒドロキシル基で置換されていても良い）、炭素数１〜６の直鎖、分岐鎖もしくは環状のアルキルカルボニル基（ここでアルキルカルボニル基の水素原子の一部または全てはハロゲン（フッ素、塩素、臭素、ヨウ素）、アミノ基もしくはヒドロキシル基で置換されていても良い）、同一かもしくは異なる３つのアルキル基からなるトリアルキルシリル基を表す。）
本発明の反応では、必要な原料はいずれも安価であり、極低温で保存、使用する必要もないため、操作は簡便であり、なおかつ廃棄物も抑制される。

Was found to be obtained in a high yield, and the above problem was solved. (In the formulas [1] to [3], R ¹ represents a hydrogen atom, a fluorine atom or a trifluoromethyl group, R ² represents a hydrogen atom, a fluorine atom or a chlorine atom. R ³ represents a hydrogen atom, phenyl or A group (wherein some or all of the hydrogen atoms of the phenyl group may be substituted with a halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group), a straight chain having 1 to 6 carbon atoms, branched A chain or cyclic alkyl group (wherein some or all of the hydrogen atoms in the alkyl group may be substituted with a halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group), 1 to 6 carbon atoms A straight chain, branched chain or aryl group (wherein some or all of the hydrogen atoms of the aryl group are substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group) Or a linear, branched or cyclic alkylcarbonyl group having 1 to 6 carbon atoms (wherein part or all of the hydrogen atoms of the alkylcarbonyl group are halogen (fluorine, chlorine, bromine, iodine), amino group or It may be substituted with a hydroxyl group), and represents a trialkylsilyl group consisting of three alkyl groups which are the same or different.
In the reaction of the present invention, all necessary raw materials are inexpensive, and it is not necessary to store and use them at extremely low temperatures. Therefore, the operation is simple, and waste is also suppressed.

  As a method for synthesizing alkyl-substituted-3-penten-1-ynes not containing a fluorine substituent, a method of reacting alkyl-substituted vinyl chlorides and terminal acetylenes in the presence of a palladium catalyst and a basic substance (non-patented) Document 6) is known. However, there has been no known example in which vinyl chlorides in which a strong electron-withdrawing functional group such as a trifluoromethyl group is directly bonded to olefinic carbon efficiently couples with terminal acetylenes.

The inventor has further found that the above-described coupling reaction proceeds particularly advantageously under certain conditions. The raw material compound represented by the formula [1] targeted by the present invention has a CF ₃ group bonded to olefin carbon. Because of the strong electron-withdrawing this CF ₃ group, the carbon on the opposite side of the olefinic bond is energetically unstable against a CF ₃ group, the reactivity of this site is conventionally known in Non-Patent Document 6 It is very different from the substrate. As a result, the compound represented by the formula [1] which is the subject of the present invention also has a large tendency to induce a side reaction. However, the inventors have also found that the target 5,5,5-trifluoro-3-penten-1-ynes are particularly useful when using a specific basic substance for reactions using such reaction substrates. The knowledge that it can manufacture with a high yield was acquired.

The reaction can produce a wide range of 5,5,5-trifluoro-3-penten-1-ynes represented by the formula [3], of which R ³ is H And a compound represented by the formula [4]

を該反応によって直接製造するためには、式［２］で表される末端アセチレンとして、無置換のアセチレンを用いる必要がある。無置換のアセチレンは反応性が高いために、煩雑な取扱いが要求される。この場合、次のように反応を２工程に分けることもできる。すなわち、末端アセチレンとして、「無置換のアセチレン」を除く、次の式［２ａ］で表される化合物

Is directly produced by the reaction, it is necessary to use unsubstituted acetylene as the terminal acetylene represented by the formula [2]. Since unsubstituted acetylene has high reactivity, complicated handling is required. In this case, the reaction can be divided into two steps as follows. That is, as the terminal acetylene, a compound represented by the following formula [2a], excluding “unsubstituted acetylene”

を用い、一旦、式［３ａ］で表される１−クロロ−２−トリフルオロメチル−エチレン類

1-chloro-2-trifluoromethyl-ethylenes represented by the formula [3a]

を合成する（第１工程）（式［２ａ］、式［３ａ］中の基Ｒ^3aは、前記の基Ｒ³から水素原子を除いた何れかの基を意味する。）。次いで、該、置換アセチレン体を、さらに塩基性物質と反応させると、基Ｒ^3aが脱離し、効率よく式［４］で表される５，５，５−トリフルオロ−３−ペンテン−１−イン類（末端アセチレン体）に誘導できる（第２工程）。これによって、取扱いの煩雑なアセチレンガスを用いることなく、式［４］で表される５，５，５−トリフルオロ−３−ペンテン−１−イン類（末端アセチレン体）を合成できる。

(First step) (the group R ^3a in the formulas [2a] and [3a] means any group obtained by removing a hydrogen atom from the group R ³ ). Next, when the substituted acetylene body is further reacted with a basic substance, the group R ^3a is eliminated, and 5,5,5-trifluoro-3-pentene-1- represented by the formula [4] is efficiently obtained. It can be derived into ins (terminal acetylene form) (second step). This makes it possible to synthesize 5,5,5-trifluoro-3-penten-1-ynes (terminal acetylene form) represented by the formula [4] without using complicated acetylene gas.

  In addition, the present inventors, through this study, have reported no previously synthesized (E) -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol, trimethyl -((E) -5,5,5-trifluoro-3-penten-1-ynyl) silane, (E) -6,6,6-trifluoro-4-hexen-2-yn-1-ol, The compounds ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene and (E) -5,5,5-trifluoro-3-penten-1-yne were found. .

  As described above, the present inventors use 5,5,5-trifluoro-3- represented by the formula [3] or the formula [4] in a high yield under mild conditions using an inexpensive raw material as a starting material. A novel method for producing penten-1-ynes was found, and further, novel compounds belonging to these 5,5,5-trifluoro-3-penten-1-ynes were found, and the present invention was completed.

That is, the present invention relates to 1-chloro-2-trifluoromethyl-ethylenes represented by the formula [1] and terminal acetylenes represented by the formula [2] in the presence of a palladium catalyst and a basic substance. A method of reacting to produce 5,5,5-trifluoro-3-penten-1-ynes represented by the formula [3] is provided. The present invention further relates to 5,5,5-trifluoro-3-penten-1-ynes (substituted acetylene compound) represented by the formula [3a] obtained by the method, wherein the substituent R ³ is other than hydrogen. And then reacting with a basic substance to provide 5,5,5-trifluoro-3-penten-1-ynes (terminal acetylene) represented by the formula [4] To do.

  The present invention further provides several novel compounds belonging to 5,5,5-trifluoro-3-penten-1-ynes.

  According to the present invention, 5,5,5-trifluoro-3-penten-1-ynes useful as raw materials for production of functional materials such as pharmaceuticals, agricultural chemicals and fluoropolymers, or synthetic intermediates are inexpensive. Using 1-chloro-2-trifluoromethyl-ethylene as a raw material, it is possible to provide a good yield and a low amount of waste such as iodide salt produced as a by-product after the reaction under mild conditions and simple operation. Play. For example, it can be obtained in a temperature range of 0 ° C. to 70 ° C. with a yield of 70% or more.

  Hereinafter, the present invention will be described in more detail. In the present invention, 1-chloro-2-trifluoromethyl-ethylenes represented by the formula [1] are reacted with terminal acetylenes represented by the formula [2], and represented by the formula [3]. The reaction for obtaining 5,5-trifluoro-3-penten-1-ynes is the main point (this reaction step is referred to as “first step”). By this “first step”, 5,5,5-trifluoro-3-penten-1-ynes represented by the formula [3] can be widely produced. On the other hand, when the target compound is 5,5,5-trifluoro-3-penten-1-ynes (terminal acetylene form) represented by the formula [4], the terminal acetylenes represented by the formula [2a] The first acetylene compound represented by the formula [3a] thus obtained is reacted with a basic substance to perform terminal acetylene represented by the formula [4]. A body can also be obtained (this reaction step is called "second step"). As described above, the present invention includes the “first step” as an essential element, and optionally adds the “second step” according to the type of the target product (Scheme 1).

まず、本発明の第１工程について説明する。第１工程は、式［１］の化合物と式［２］の化合物を、パラジウム触媒と塩基性物質の存在下で反応させて、式［３］の化合物を得る工程である。

First, the first step of the present invention will be described. The first step is a step of obtaining a compound of the formula [3] by reacting the compound of the formula [1] with the compound of the formula [2] in the presence of a palladium catalyst and a basic substance.

  Examples of 1-chloro-2-trifluoromethyl-ethylenes represented by the formula [1] which are starting materials of the present invention include 1-chloro-3,3,3-trifluoropropene and 1-chloro-2. -Fluoro-3,3,3-trifluoropropene, 1-chloro-2-trifluoromethyl-3,3,3-trifluoropropene, 1-chloro-1-fluoro-3,3,3-trifluoropropene 1-chloro-1,2-difluoro-3,3,3-trifluoropropene, 1-chloro-1-fluoro-2-trifluoromethyl) -3,3,3-trifluoropropene, 1,1- Dichloro-3,3,3-trifluoropropene, 1,1-dichloro-2-fluoro-3,3,3-trifluoropropene, 1,1-dichloro-2-trifluoromethyl-3,3,3- Trifluoro Such as Ropen is preferable. These 1-chloro-2-trifluoromethyl-ethylenes have cis isomers (Z isomers) and trans isomers (E isomers) as stereoisomers depending on the type of substituent, but these are not particularly limited. By a one-step reaction, 5,5,5-trifluoro-3-penten-1-ynes can be obtained while maintaining the cis and trans structures of the double bond site. A single isomer or a mixture of both isomers can be used.

  Among these, (E) -1-chloro-3,3,3-trifluoropropene, which is industrially produced as HCFC-1233zd, is particularly preferable because of its availability and the usefulness of the resulting compound. When (E) -1-chloro-3,3,3-trifluoropropene is used as a raw material, the result of the reaction in the first step is represented by formula (5) (E) -5, 5, 5-Trifluoro-3-penten-1-ynes

である。該化合物のうち、Ｒ³基が水素を除く基（Ｒ^3a）である場合には、これをさらに第２工程の反応に付すと、Ｒ^3a基が脱離し、（Ｅ）−５，５，５−トリフルオロ−３−ペンテン−１−インが得られる（下記スキーム２を参照）。

It is. Among these compounds, when the R ³ group is a group excluding hydrogen (R ^3a ), when this is further subjected to the reaction in the second step, the R ^3a group is eliminated and (E) -5, 5, 5-Trifluoro-3-penten-1-yne is obtained (see Scheme 2 below).

式［２］で表される末端アセチレン類のＲ³基としては、水素原子、フェニル基（ここでフェニル基の水素原子の一部または全てはハロゲン（フッ素、塩素、臭素、ヨウ素）、アミノ基もしくはヒドロキシル基で置換されていても良い）、炭素数１〜６の直鎖、分岐鎖もしくは環状のアルキル基（ここでアルキル基の水素原子の一部または全てはハロゲン（フッ素、塩素、臭素、ヨウ素）、アミノ基もしくはヒドロキシル基で置換されていても良い）、炭素数１〜６の直鎖、分岐鎖もしくはアリール基（ここでアリール基の水素原子の一部または全てはハロゲン（フッ素、塩素、臭素、ヨウ素）、アミノ基もしくはヒドロキシル基で置換されていても良い）、炭素数１〜６の直鎖、分岐鎖もしくは環状のアルキルカルボニル基（ここでアルキルカルボニル基の水素原子の一部または全てはハロゲン（フッ素、塩素、臭素、ヨウ素）、アミノ基もしくはヒドロキシル基で置換されていても良い）、同一かもしくは異なる３つのアルキル基からなるトリアルキルシリル基から選ぶことができる。

As the R ³ group of the terminal acetylene represented by the formula [2], a hydrogen atom, a phenyl group (wherein some or all of the hydrogen atoms of the phenyl group are halogen (fluorine, chlorine, bromine, iodine), amino group Alternatively, it may be substituted with a hydroxyl group), a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms (wherein some or all of the hydrogen atoms of the alkyl group are halogen (fluorine, chlorine, bromine, Iodine), which may be substituted with an amino group or a hydroxyl group), a linear, branched or aryl group having 1 to 6 carbon atoms (wherein some or all of the hydrogen atoms of the aryl group are halogen (fluorine, chlorine) , Bromine, iodine), which may be substituted with an amino group or a hydroxyl group), a straight-chain, branched-chain or cyclic alkylcarbonyl group having 1 to 6 carbon atoms (wherein alkyl Some or all of the hydrogen atoms of the carbonyl group may be substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group), a trialkylsilyl group comprising three identical or different alkyl groups You can choose from.

  Among the terminal acetylenes represented by the formula [2], phenylacetylene, 2-methyl-3-butyn-2-ol, trimethylsilylacetylene, propargyl alcohol and the like are easily available industrially and have excellent reactivity. Therefore, it is particularly preferably used.

  There is no particular limitation on the amount ratio of 1-chloro-2-trifluoromethyl-ethylenes represented by the formula [1] and terminal acetylene represented by the formula [2]. The amount of the compound of formula [2] used per 1 mol of the compound is in the range of 0.8 to 50 mol, preferably 0.8 to 10 mol, more preferably 1 to 3 mol.

Specific examples of the palladium catalyst used for the reaction in the first step include palladium-supported activated carbon, palladium chloride, palladium acetate, tetrakis (triphenylphosphine) palladium, bis (dibenzylideneacetonato) palladium, PdCl ₂ [P ( o-Me-Ph) ₃ ] ₂ , PdCl ₂ [P (m-Me-Ph) ₃ ] ₂ , PdCl ₂ [P (p-Me-Ph) ₃ ] ₂ , PdCl ₂ (PMe ₃ ) ₂ , PdBr ₂ (PPh ₃ ) ₂ , PdCl ₂ [P (Ph) ₂ CH ₂ CH ₂ P (Ph) ₂ ], PdCl ₂ [P (Ph) ₂ CH ₂ CH ₂ CH ₂ CH ₂ P (Ph) ₂ ], PdCl _{2 (PhCN) 2, Pd (CO} ) (PPh 3) 3, PhPdI (PPh 3) 2, PhPdBr (PPh 3) 2, PhPdBr (PMePh 2) 2, PdCl 2 (PMePh 2) 2, P _{Cl 2 (PEt 2 Ph) 2} , PdCl 2 (PMe 2 Ph) 2, Pd 2 Br 4 (PPh 3) 2, PdCl 2 [P (Ph) 3] 2 and the like are preferable. Here, Ph represents a phenyl group, Me represents a methyl group, Et represents an ethyl group, o- represents ortho substitution, m- represents meta substitution, and p- represents para substitution.

All of these show satisfactory catalytic activity, but divalent Pd complexes such as palladium chloride, palladium acetate, and PdCl ₂ [P (Ph) ₃ ] ₂ that are inexpensive and easy to handle are particularly preferred economically. Regarding the reaction of the present invention, an expensive zero-valent Pd complex, which is often required for a general coupling reaction, is not always required, and can be said to be an advantage of the present invention.

  The amount of the palladium catalyst used in the first step can be appropriately selected in the range of 0.0001 to 0.2 mol per mol of the compound represented by the formula [1], but preferably 0.001 to 0.1. Mol, more preferably 0.001 to 0.05 mol.

The first step proceeds with only the palladium catalyst, but it is particularly preferable to use a trivalent phosphorus compound as a cocatalyst because the activity of the palladium complex is easily maintained. Here, the co-catalyst refers to a substance added in a small amount in order to increase the activity or selectivity of the catalyst. They include the formula [6]
R ^4- (R ^5- ) PR ⁶ [6]
(In the formula [6], R ⁴ , R ⁵ and R ⁶ represent the same or different alkyl group, aryl group, alkoxy group, aryloxy group or halogen atom.)
And specifically, tri-n-butylphosphine, triethylphosphine, triphenylphosphine, tri-o-tolylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, tri-o -Tolyl phosphite, phosphorus trichloride and the like are exemplified. In addition to this, the formula [7]
_{^{(R 4) 2 P-Q}} -P (R 5) 2 [7]
(Wherein [7], R ⁴ and R ⁵ are as defined above, Q is - (CH _{2) m} - (alkylene m is preferably from integers of 1 to 8 which is represented by an integer from 1 to 4).. Represents a group)
The phosphine represented by these is also preferable. Specifically, 1,1′-bis (diphenylphosphino) ferrocene, 1,4-bis (diphenylphosphino) butane, 1,3-bis (diphenylphosphino) propane, 1,2-bis (diphenylphosphino) ) Ethane can be exemplified. The amount of these phosphorus compounds used can be appropriately selected in the range of 0.5 to 50 mol per mol of the above metal catalyst.

The trivalent phosphorus compound referred to here may be a free compound of its own, or may be one previously incorporated as a ligand in a palladium catalyst, such as PdCl ₂ [P (Ph) ₃ ] _2. May be used in combination.

  When the first step is performed, the yield may be improved by adding a monovalent copper compound. In such a case, a copper compound may be added as a copper catalyst. Examples of the monovalent copper compound to be used include copper iodide, copper bromide, copper chloride, copper oxide, copper cyanide and the like, and copper iodide is particularly preferable. In general, the range of 0.0001 to 0.5 mol can be appropriately selected per 1 mol of the compound, preferably 0.001 to 0.1 mol, and more preferably 0.001 to 0.05 mol. Of course, it is possible to use more than this, but there is no merit to use in large quantities.

  Although there is no special restriction | limiting in the basic substance used for a 1st process, Organic amines which are bases which have moderate intensity | strength are preferable. Although there is no special restriction as organic amines, C1-C10 chain monoalkylamine, C1-C10 chain dialkylamine, C5-C12 cyclic monoalkylamine, carbon Use of a cyclic dialkylamine having 5 to 12 carbon atoms and an aromatic amine having 5 to 12 carbon atoms is particularly preferable because the desired reaction rate and selectivity are improved. Specific examples include methylamine, ethylamine, isopropylamine, n-butylamine, dimethylamine, diethylamine, triethylamine, di-isopropylethylamine, di-n-butylamine, tri-n-butylamine, tetramethylethylenediamine, N, N-dimethyl. Examples include aniline, N, N-diethylaniline, pyridine, lutidine, 2-methylpyridine, N-methylmorpholine, piperidine, pyrrolidine, morpholine, dibutylamine, and diisopropylamine, with diethylamine being particularly preferred.

In contrast, inorganic bases (for example, alkali metal or alkaline earth metal carbonates (sodium carbonate, potassium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, etc.), carboxylic acids Salts (sodium acetate, potassium acetate, etc.), metal alkoxides (sodium methoxide, sodium ethoxide, etc.), hydroxides (sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.) and highly basic organic bases {e.g. , Guanidine, 1,8-diazabicyclo [5,4,0] -7-undecene, etc.}, the elimination of the R ³ group is likely to compete and the yield of the desired coupling product decreases. There is.

  Although the usage-amount of a base can select suitably the range of 1-50 mol normally with respect to 1 mol of compounds of Formula [1], Preferably it is 1-20 mol, More preferably, it is 1-10 mol. .

  The above reaction is usually performed in an inert gas such as nitrogen or argon. Usually, the reaction temperature is -50 ° C to 160 ° C, preferably -10 ° C to 100 ° C, more preferably -5 ° C to 50 ° C. Further, the pressure is not particularly limited, but the reaction can be performed under an atmospheric pressure by introducing an inert gas, or the reaction can be performed under a pressurized condition by sealing. Since 1-chloro-2-trifluoromethyl-ethylenes as raw materials generally have a low boiling point, an important point in carrying out this step is to liquefy them or dissolve them in a solvent. It is to keep. Appropriate temperatures and pressures are selected to accomplish this.

  When the reaction is performed at room temperature or lower, the reaction can be performed under an inert gas atmosphere at atmospheric pressure, which is particularly preferable because it is simple. On the other hand, when heated, 1-chloro-2-trifluoromethyl-ethylenes may vaporize. When 1-chloro-2-trifluoromethyl-ethylene is vaporized, the reaction hardly proceeds and the desired product cannot be obtained. In this case, since the raw material 1-chloro-2-trifluoromethyl-ethylene is liquefied or dissolved in a solvent, an autoclave is used as a reaction vessel, and the inside of the vessel is brought to an inert gas atmosphere. After that, it is preferable to carry out the reaction under pressure conditions after sealing.

  In addition to the target coupling reaction, the following enamine compound is included in the reaction of the first step:

の生成が競合する。このエナミン化合物は、式［１］の化合物と、式［２］の化合物から、Ｐｄ触媒の有無に関わらず生成する化合物である。このエナミン化合物の副生は、ジエチルアミン等の鎖状アミンを使用すると特に抑制しやすい。ジエチルアミン等の鎖状アミンを使用すると、後述の実施例に示すように、室温もしくはそれ以下の温度でも、目的とする反応が十分な速度で進行するため、大気圧でも反応を実施できる。一方、ピペリジン等の環状アミンを使用する場合は、エナミン化合物が有意に副生することがある（実施例１参照）が、この場合に限り、温度を高め（例えば４０℃以上）に設定すると、目的とする触媒反応が優先し、目的物を高い選択率で得られるようになる（実施例２参照）。このように、第１工程の反応温度、圧力は、当業者により適宜最適化することが望ましい。

Production conflicts. This enamine compound is a compound produced from the compound of the formula [1] and the compound of the formula [2] regardless of the presence or absence of a Pd catalyst. This by-product of the enamine compound is particularly easily suppressed when a chain amine such as diethylamine is used. When a chain amine such as diethylamine is used, the target reaction proceeds at a sufficient rate even at room temperature or lower, as shown in the examples described later, so that the reaction can be carried out even at atmospheric pressure. On the other hand, when a cyclic amine such as piperidine is used, an enamine compound may be significantly produced as a by-product (see Example 1), but only in this case, if the temperature is increased (for example, 40 ° C. or higher), The target catalytic reaction is prioritized and the target product can be obtained with high selectivity (see Example 2). Thus, it is desirable to optimize the reaction temperature and pressure in the first step as appropriate by those skilled in the art.

  In the first step, a suitable solvent such as acetonitrile, tetrahydrofuran, dioxane, diethyl ether, dimethylformamide, dimethyl sulfoxide, hexamethylphosphorylamide, N-methylpyrrolidone, methanol, toluene, n-hexane, n-heptane, etc. is used as a reaction solvent. It can also be used as When the above basic substance is a liquid, these bases (for example, diethylamine, piperidine and the like) also serve as a solvent, so that it is not necessary to add a separate solvent.

  The amount of solvent can be optimized by one skilled in the art so that a sufficient amount of the reagent dissolves and the reaction proceeds smoothly.

  The reaction time is not particularly limited and depends on the temperature and the amount of catalyst, so the progress of the reaction should be traced by means such as gas chromatography, and the reaction should be terminated after confirming that the reaction end point has been approached. Is desirable.

  After completion of the reaction, 5,5,5-trifluoro-3-penten-1-ynes which are substituted acetylenes can be obtained by ordinary operations such as extraction, distillation, recrystallization and the like.

  Next, the second step of the present invention will be described in detail. The second step is a step of obtaining a terminal acetylene body represented by the formula [4] by reacting the substituted acetylene body represented by the formula [3a] with a basic substance. The reaction in the second step can be carried out after isolating and purifying the substituted acetylene compound represented by the formula [3a] by a purification operation after completion of the reaction in the first step, but the first step without purification. The base can also be added directly to the reaction mixture.

The reaction in the second step is an elimination reaction of the R ^3a group. Therefore, there is little practical benefit in using a complicated and expensive R ^3a . As the compound of the formula [2a] used in the second step, a compound that is easy to cause elimination, such as 2-methyl-3-butyn-2-ol, trimethylsilylacetylene, and the like, is preferable.

  The basic substance used in the second step is preferably an inorganic base or a strong organic base. Examples of the inorganic base include lithium hydroxide, sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate, potassium bicarbonate, sodium hydride, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert. -Butoxide, potassium fluoride, sodium fluoride, tetrabutylammonium fluoride and the like are preferable. As the organic strong base, guanidine, 1,8-diazabicyclo [5,4,0] -7-undecene and the like are preferable. From an economical viewpoint, inorganic bases such as sodium carbonate and potassium carbonate are particularly preferred.

Even in the second step, the target reaction proceeds even when the organic amines preferably used in the first step (triethylamine, diethylamine, piperidine, pyrrolidine, etc.) are used. As can be seen from the fact that it is suitable for use in one step, since the ability to remove the R ^3a group is weak, using these in the second step often requires a long time for the reaction, which is not preferable.

  In the second step, the basic substance is generally used in an amount of 1 to 10 mol, preferably 1 to 5 mol, per 1 mol of the compound of the formula [3a].

  The second step is preferably carried out in the presence of a solvent. The solvent is not particularly limited as long as it does not participate in the reaction. For example, hydrocarbons such as hexane and benzene, ethers such as diethyl ether, tetrahydrofuran and dioxane, halogenated hydrocarbons such as dichloromethane and chloroform, acetone and the like Examples include alkyl ketones, alcohols such as methanol, ethanol, ethylene glycol, diethylene glycol, and glycerin, aprotic polar solvents such as acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide, and hexamethylphosphate triamide, and water. Of these, alcohols such as methanol, ethanol, ethylene glycol, diethylene glycol, and glycerin are particularly preferably used.

  Although the reaction temperature of a 2nd process is not specifically limited, Usually, it is -50 degreeC-100 degreeC, Preferably it is -10 degreeC-100 degreeC, More preferably, it is the range of -5 degreeC-30 degreeC.

The treatment after the reaction in the second step is not particularly limited. However, the target formula may be obtained by a method of directly distilling the reaction solution, or by adding water or ice water and then performing an ordinary operation such as extraction with organic solvent and distillation. 4], 5,5,5-trifluoro-3-penten-1-yne (terminal acetylene) can be obtained.
The present invention will be described in more detail with reference to examples below, but the present invention is not limited thereto.

Production of ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene

窒素雰囲気下、（Ｅ）−１−クロロ−３，３，３−トリフルオロプロペン４．０ｇ（３０．７ｍｍｏｌ）をテトラヒドロフラン２０ｍｌに溶かし、ピペリジン３ｍＬ（３０．７ｍｍｏｌ）、フェニルアセチレン（３．４ｍＬ、３０．７ｍｍｏｌ）、ビス（ジベンジリデンアセトナト）パラジウム２６５ｍｇ（０．６１ｍｍｏｌ）、トリフェニルホスフィン４８３ｍｇ（１．８４ｍｍｏｌ）、ヨウ化銅（Ｉ）１１７ｍｇ（０．６１ｍｍｏｌ）を氷冷下加えた後、２４時間撹拌した。反応液をガスクロマトグラフィー（ＧＣ）で分析したところ、目的化合物である（（Ｅ）−５，５，５−トリフルオロ−３−ペンテン−１−イニル）ベンゼンが３８％、ピペリジンと（Ｅ）−１−クロロ−３，３，３−トリフルオロプロペンとが反応することにより生じたエナミンが３７％生成しており、未反応分のフェニルアセチレンは１４％であった。（なお、目的化合物の単離精製は本実施例では行っていない）。

Under a nitrogen atmosphere, 4.0 g (30.7 mmol) of (E) -1-chloro-3,3,3-trifluoropropene was dissolved in 20 ml of tetrahydrofuran, piperidine 3 mL (30.7 mmol), phenylacetylene (3.4 mL, 30.7 mmol), 265 mg (0.61 mmol) of bis (dibenzylideneacetonato) palladium, 483 mg (1.84 mmol) of triphenylphosphine, and 117 mg (0.61 mmol) of copper (I) iodide were added under ice cooling, Stir for 24 hours. When the reaction solution was analyzed by gas chromatography (GC), it was found that the target compound ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene was 38%, piperidine and (E) 37% of the enamine produced by the reaction with -1-chloro-3,3,3-trifluoropropene was produced, and the unreacted phenylacetylene was 14%. (Note that the target compound is not isolated and purified in this example).

Production of ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene In a 100 mL stainless steel pressure vessel equipped with a stirrer and a thermometer protective tube, (E) -1-chloro-3, 4.0 g (30.7 mmol) of 3,3-trifluoropropene was dissolved in 15 ml of tetrahydrofuran, and piperidine 3 mL (30.7 mmol), phenylacetylene (3.4 mL, 30.7 mmol), tetrakis (triphenylphosphine) palladium 177 mg ( 0.15 mmol) and 117 mg (0.61 mmol) of copper (I) iodide were added under ice cooling, and then the inside of the pressure vessel was pressurized with nitrogen gas to a pressure of 1 MPa and stirred at 70 ° C. for 72 hours. After 72 hours, it was cooled to ice and then returned to normal pressure. When the reaction solution was analyzed by gas chromatography (GC), 79% of the target compound ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene was produced. And (E) -1-chloro-3,3,3-trifluoropropene reacted with each other, and no enamine was produced. The amount of unreacted phenylacetylene was 14%. (Note that the target compound is not isolated and purified in this example).

Production of ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene In a nitrogen atmosphere, 4.0 g of (E) -1-chloro-3,3,3-trifluoropropene ( 30.7 mmol) is dissolved in 15 ml of tetrahydrofuran, and 3.2 mL (30.7 mmol) of diethylamine, 3.4 mL, 30.7 mmol of phenylacetylene, 177 mg (0.15 mmol) of tetrakis (triphenylphosphine) palladium, copper iodide ( I) 117 mg (0.61 mmol) was added under ice cooling, followed by stirring for 24 hours. When the reaction solution was analyzed by gas chromatography (GC), 86% of the target compound ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene was produced. And (E) -1-chloro-3,3,3-trifluoropropene reacted with each other, and no enamine was produced. The unreacted amount of phenylacetylene was 12%. (Note that the target compound is not isolated and purified in this example).

(E) Production of -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol

窒素雰囲気下、（Ｅ）−１−クロロ−３，３，３−トリフルオロプロペン４．０ｇ（３０．７ｍｍｏｌ）をテトラヒドロフラン１５ｍｌに溶かし、ジエチルアミン３．２ｍＬ（３０．７ｍｍｏｌ）、２−メチル−３−ブチン−２−オール２．８ｍｌ（３０．７ｍｍｏｌ）、テトラキス（トリフェニルホスフィン）パラジウム１７７ｍｇ（０．１５ｍｍｏｌ）、ヨウ化銅（Ｉ）１１７ｍｇ（０．６１ｍｍｏｌ）を氷冷下加えた後、４０時間撹拌した。反応液をガスクロマトグラフィー（ＧＣ）で分析したところ、目的化合物である（Ｅ）−７，７，７−トリフルオロ−２−メチル−５−ヘプテン−３−イン−２−オールが８９％生成していた。ジエチルアミンと（Ｅ）−１−クロロ−３，３，３−トリフルオロプロペンとが反応したエナミンは生成していなかった。２−メチル−３−ブチン−２−オールは完全に消費された。（なお、この目的化合物の単離精製は本実施例では行っていない）。

Under a nitrogen atmosphere, 4.0 g (30.7 mmol) of (E) -1-chloro-3,3,3-trifluoropropene was dissolved in 15 ml of tetrahydrofuran, and 3.2 mL (30.7 mmol) of diethylamine, 2-methyl-3 -After adding 2.8 ml (30.7 mmol) of butyn-2-ol, 177 mg (0.15 mmol) of tetrakis (triphenylphosphine) palladium and 117 mg (0.61 mmol) of copper (I) iodide under ice-cooling, Stir for hours. When the reaction solution was analyzed by gas chromatography (GC), 89% of the target compound (E) -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol was produced. Was. Enamine obtained by reacting diethylamine with (E) -1-chloro-3,3,3-trifluoropropene was not produced. 2-Methyl-3-butyn-2-ol was completely consumed. (Note that this target compound was not isolated and purified in this example).

(E) Preparation of -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol Under a nitrogen atmosphere, (E) -1-chloro-3,3,3-trifluoro 4.0 g (30.7 mmol) of propene was dissolved in 15 ml of tetrahydrofuran, 3.2 mL (30.7 mmol) of diethylamine, 2.8 ml (30.7 mmol) of 2-methyl-3-butyn-2-ol, palladium (II) acetate 103 mg (0.15 mmol), 161 mg (0.6 mmol) of triphenylphosphine, and 117 mg (0.61 mmol) of copper (I) iodide were added under ice cooling, followed by stirring for 40 hours. When the reaction solution was analyzed by gas chromatography (GC), 76% of the target compound (E) -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol was produced. Was. Enamine obtained by reacting diethylamine with (E) -1-chloro-3,3,3-trifluoropropene was not produced. 2-Methyl-3-butyn-2-ol was completely consumed. (Note that this target compound was not isolated and purified in this example).

(E) Preparation of -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol Under a nitrogen atmosphere, (E) -1-chloro-3,3,3-trifluoro Propene 4.0 g (30.7 mmol) was dissolved in diethylamine 10 mL (98.2 mmol), 2-methyl-3-butyn-2-ol (3.0 mL, 30.7 mmol), palladium (II) acetate 34 mg (. 154 mmol), 161 mg (0.61 mmol) of triphenylphosphine, and 117 mg (0.61 mmol) of copper (I) iodide were added under ice cooling, followed by stirring for 15 hours. The reaction was filtered. The filtrate was distilled under reduced pressure (96 ° C./10.4 kPa), and the target compound (E) -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol 4.0 g (Yield 73%, purity 91%) was obtained as a pale yellow liquid.
[Physical properties of (E) -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol]
¹ H-NMR spectrum (400 MHz, CDCl ₃ ) δ (ppm): 1.48 (3H, s), 1.48 (3H, s), 3.35 (1H, br.s) 5.98 (1H, dqd, J = 15.8, 6.9, 1.8Hz), 6.21 (1H, dq, J = 16.1, 2.2Hz).
¹⁹ F-NMR spectrum (400 MHz, CDCl ₃ ): −65.5 ppm (3F, br.s) (CFCl ₃ = 0 ppm).

(E) Preparation of -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol Under a nitrogen atmosphere, (E) -1-chloro-3,3,3-trifluoro Propene 4.0 g (30.7 mmol) was dissolved in diethylamine 10 mL (98.2 mmol), 2-methyl-3-butyn-2-ol (3.0 mL, 30.7 mmol), palladium (II) chloride 27 mg (. 154 mmol), 80 mg (0.31 mmol) of triphenylphosphine, and 117 mg (0.61 mmol) of copper (I) iodide were added under ice cooling, followed by stirring for 15 hours. The reaction was filtered. The filtrate was distilled under reduced pressure (93 ° C./7.3 kPa), and 3.9 g of the target compound (E) -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol. (Yield 72%, purity 97.5%) was obtained as a pale yellow liquid.

Preparation of trimethyl-((E) -5,5,5-trifluoro-3-penten-1-ynyl) silane

窒素雰囲気下、（Ｅ）−１−クロロ−３，３，３−トリフルオロプロペン２０．０ｇ（１５４ｍｍｏｌ）をジエチルアミン６４ｍＬ（６１３ｍｍｏｌ）に溶かし、トリメチルシリルアセチレン１５．１ｇ（１５３．５ｍｍｏｌ）、酢酸パラジウム（ＩＩ）１７０ｍｇ（０．７７ｍｍｏｌ）、トリフェニルホスフィン８０５ｍｇ（３．０５ｍｍｏｌ）、ヨウ化銅（Ｉ）５８５ｍｇ（３．０５ｍｍｏｌ）を氷冷下加えた後、１５時間撹拌した。反応液にペンタンを加え濾過した後、濾液を１ＮのＨＣｌ水溶液で洗浄した。溶媒留去した後、減圧蒸留(７６℃／２４．５ｋＰａ)し、目的化合物である、トリメチル−（（Ｅ）−５，５，５−トリフルオロ−３−ペンテン−１−イニル）シラン ２６．０ｇ（収率８３％・純度９５％）を淡黄色液体として得た。
［トリメチル−（（Ｅ）−５，５，５−トリフルオロ−３−ペンテン−１−イニル）シランの物性］
¹H-NMRスペクトル(400MHz，CDCl₃)δ(ppm)：0.19 (9H, s), 6.07 (1H, dq, J=15.9, 6.6 Hz), 6.24 (1H, dq, J=15.9, 2.0 Hz).
¹⁹F-NMRスペクトル(400MHz，CDCl₃)：−65.5 ppm(3F, d, J=6.0 Hz) (CFCl₃=0 ppm).

Under a nitrogen atmosphere, 20.0 g (154 mmol) of (E) -1-chloro-3,3,3-trifluoropropene was dissolved in 64 mL (613 mmol) of diethylamine, and 15.1 g (153.5 mmol) of trimethylsilylacetylene, palladium acetate ( II) 170 mg (0.77 mmol), 805 mg (3.05 mmol) of triphenylphosphine, and 585 mg (3.05 mmol) of copper (I) iodide were added under ice cooling, followed by stirring for 15 hours. After adding pentane to the reaction solution and filtering, the filtrate was washed with 1N HCl aqueous solution. After distilling off the solvent, distillation under reduced pressure (76 ° C./24.5 kPa) was performed, and the target compound, trimethyl-((E) -5,5,5-trifluoro-3-penten-1-ynyl) silane, 26. 0 g (yield 83%, purity 95%) was obtained as a pale yellow liquid.
[Physical properties of trimethyl-((E) -5,5,5-trifluoro-3-penten-1-ynyl) silane]
¹ H-NMR spectrum (400 MHz, CDCl ₃ ) δ (ppm): 0.19 (9H, s), 6.07 (1H, dq, J = 15.9, 6.6 Hz), 6.24 (1H, dq, J = 15.9, 2.0 Hz) .
¹⁹ F-NMR spectrum (400 MHz, CDCl ₃ ): −65.5 ppm (3F, d, J = 6.0 Hz) (CFCl ₃ = 0 ppm).

Production of ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene In a nitrogen atmosphere, 4.0 g of (E) -1-chloro-3,3,3-trifluoropropene ( 30.7 mmol) was dissolved in diethylamine 10 mL (98.2 mmol), phenylacetylene (3.3 mL, 30.7 mmol), palladium (II) acetate 34 mg (0.154 mmol), triphenylphosphine 161 mg (0.61 mmol), iodine After adding 117 mg (0.61 mmol) of copper (I) chloride under ice cooling, the mixture was stirred for 15 hours. The reaction was filtered. The filtrate was distilled under reduced pressure (70 ° C./0.67 kPa), and 4.6 g (yield 76%) of ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene as the target compound. -Purity 99%) was obtained as a colorless transparent liquid.
[Physical properties of ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene]
¹ H-NMR spectrum (400 MHz, CDCl ₃ ) δ (ppm): 6.06 (1H, dq, J = 15.8, 6.8 Hz), 6.40 (1H, dq, J = 15.8, 2.2 Hz), 7.31-7.15 (3H, m), 7.37-7.40 (2H, m).
¹⁹ F-NMR spectrum (400 MHz, CDCl ₃ ): −65.2 ppm (3F, d, J = 6.0 Hz) (CFCl ₃ = 0 ppm).

Production of (E) -6,6,6-trifluoro-4-hexen-2-yn-1-ol

窒素雰囲気下、（Ｅ）−１−クロロ−３，３，３−トリフルオロプロペン１０．０ｇ（７７ｍｍｏｌ）をジエチルアミン３２ｍＬ（３０７ｍｍｏｌ）に溶かし、プロパルギルアルコール４．４ｍＬ（７７ｍｍｏｌ）、酢酸パラジウム（ＩＩ）８５ｍｇ（０．３８ｍｍｏｌ）、トリフェニルホスフィン４０３ｍｇ（１．５３ｍｍｏｌ）、ヨウ化銅（Ｉ）２９２ｍｇ（１．５３ｍｍｏｌ）を氷冷下加えた後、１５時間撹拌した。反応液に酢酸エチルを加え濾過した後、濾液を１ＮのＨＣｌ水溶液で洗浄した。溶媒留去した後、減圧蒸留(９６℃／６．０ｋＰａ)し、目的化合物である、（Ｅ）−６，６，６−トリフルオロ−４−ヘキセン−２−イン−１−オール ９．５ｇ（収率８２％・純度９５％）を淡黄色液体として得た。
［（Ｅ）−６，６，６−トリフルオロ−４−ヘキセン−２−イン−１−オールの物性］
¹H-NMRスペクトル(400MHz，CDCl₃)δ(ppm)：2.00 (1H, br.s), 4.36 (2H, s), 6.01 (1H, dq, J=16.1, 6.6 Hz), 6.23 (1H, dq, J=15.8, 2.2 Hz).
¹⁹F-NMRスペクトル(400MHz，CDCl₃)：−65.5 ppm(3F, d, J=6.0 Hz) (CFCl₃=0 ppm).

Under a nitrogen atmosphere, 10.0 g (77 mmol) of (E) -1-chloro-3,3,3-trifluoropropene was dissolved in 32 mL (307 mmol) of diethylamine, 4.4 mL (77 mmol) of propargyl alcohol, and palladium (II) acetate. 85 mg (0.38 mmol), 403 mg (1.53 mmol) of triphenylphosphine, and 292 mg (1.53 mmol) of copper (I) iodide were added under ice cooling, followed by stirring for 15 hours. After adding ethyl acetate to the reaction solution and filtering, the filtrate was washed with 1N HCl aqueous solution. After the solvent was distilled off, distillation under reduced pressure (96 ° C./6.0 kPa) was carried out, and 9.5 g of the target compound (E) -6,6,6-trifluoro-4-hexen-2-in-1-ol. (Yield 82%, purity 95%) was obtained as a pale yellow liquid.
[Physical properties of (E) -6,6,6-trifluoro-4-hexen-2-yn-1-ol]
¹ H-NMR spectrum (400 MHz, CDCl ₃ ) δ (ppm): 2.00 (1H, br.s), 4.36 (2H, s), 6.01 (1H, dq, J = 16.1, 6.6 Hz), 6.23 (1H, dq, J = 15.8, 2.2 Hz).
¹⁹ F-NMR spectrum (400 MHz, CDCl ₃ ): −65.5 ppm (3F, d, J = 6.0 Hz) (CFCl ₃ = 0 ppm).

(E) Production of 5,5,5-trifluoro-3-penten-1-yne

氷冷下、トリメチル−（（Ｅ）−５，５，５−トリフルオロ−３−ペンテン−１−イニル）シラン５ｇ（２６ｍｍｏｌ）にエチレングリコール５ｇ、炭酸カリウム３．６ｇ（２６ｍｍｏｌ）を加え、１２時間攪拌した。反応液を減圧蒸留(３６℃／１０１．１ｋＰａ)し、目的化合物である、（Ｅ）−５，５，５−トリフルオロ−３−ペンテン−１−イン ２．７ｇ（収率８６％・純度９１％）を無色液体として得た。
［（Ｅ）−５，５，５−トリフルオロ−３−ペンテン−１−インの物性］
¹H-NMRスペクトル(400MHz，CDCl₃)δ(ppm)：3.22 (1H, br s), 6.17 (1H, dq, J=16.1, 7.3 Hz), 6.26 (1H, dq, J=17.8, 2.2 Hz).
¹⁹F-NMRスペクトル(400MHz，CDCl₃)：−65.8 ppm(3F, br d, J=6.0 Hz) (CFCl₃=0 ppm).

Under ice cooling, 5 g (26 mmol) of trimethyl-((E) -5,5,5-trifluoro-3-penten-1-ynyl) silane was added with 5 g of ethylene glycol and 3.6 g (26 mmol) of potassium carbonate. Stir for hours. The reaction solution was distilled under reduced pressure (36 ° C./101.1 kPa), and 2.7 g (yield 86%, purity), which was the target compound, (E) -5,5,5-trifluoro-3-penten-1-yne. 91%) as a colorless liquid.
[Physical properties of (E) -5,5,5-trifluoro-3-penten-1-yne]
¹ H-NMR spectrum (400 MHz, CDCl ₃ ) δ (ppm): 3.22 (1H, br s), 6.17 (1H, dq, J = 16.1, 7.3 Hz), 6.26 (1H, dq, J = 17.8, 2.2 Hz ).
¹⁹ F-NMR spectrum (400 MHz, CDCl ₃ ): −65.8 ppm (3F, br d, J = 6.0 Hz) (CFCl ₃ = 0 ppm).

Claims (11)

1-Chloro-2-trifluoromethyl-ethylenes represented by the formula [1]

And terminal acetylenes represented by the formula [2]

5,5,5-trifluoro-3-penten-1-ynes represented by the formula [3] by reacting with a palladium catalyst in the presence of a basic substance

How to manufacture.
(In the formula, R ¹ represents a hydrogen atom, a fluorine atom or a trifluoromethyl group, R ² represents a hydrogen atom, a fluorine atom or a chlorine atom. R ³ represents a hydrogen atom, a phenyl group (here, Some or all of the hydrogen atoms may be substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group), linear, branched or cyclic alkyl groups having 1 to 6 carbon atoms ( Here, some or all of the hydrogen atoms of the alkyl group may be substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group), straight chain, branched chain or 1 to 6 carbon atoms. An aryl group (wherein some or all of the hydrogen atoms in the aryl group may be substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group), carbon A linear, branched or cyclic alkylcarbonyl group of 1 to 6 (wherein some or all of the hydrogen atoms of the alkylcarbonyl group are substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group. It represents a trialkylsilyl group consisting of three identical or different alkyl groups.) 5,5,5-trifluoro-3-penten-1-ynes represented by formula [4] (terminal acetylene form) consisting of the following two steps

Manufacturing method.
First step: 1-chloro-2-trifluoromethyl-ethylenes represented by the formula [1]

And terminal acetylenes represented by the formula [2a]

Is reacted with a palladium catalyst in the presence of a basic substance to give 5,5,5-trifluoro-3-penten-1-ynes (substituted acetylene) represented by the formula [3a]

Obtaining.
Second step: 5,5,5-trifluoro-3-penten-1-yne (substituted acetylene) represented by the formula [3a] obtained in the first step is reacted with a basic substance, and the formula [3a] 4] A process for producing 5,5,5-trifluoro-3-penten-1-ynes (terminal acetylene form) represented by [4].
(In the formula, R ¹ represents a hydrogen atom, a fluorine atom or a trifluoromethyl group, R ² represents a hydrogen atom, a fluorine atom or a chlorine atom. R ^3a represents a phenyl group (here, the hydrogen atom of the phenyl group) Part or all of them may be substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group, linear, branched or cyclic alkyl group having 1 to 6 carbon atoms (wherein alkyl Some or all of the hydrogen atoms in the group may be substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group, straight chain, branched chain or aryl group having 1 to 6 carbon atoms ( Here, some or all of the hydrogen atoms of the aryl group may be substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group, and C 1-6. A linear, branched or cyclic alkylcarbonyl group (wherein some or all of the hydrogen atoms of the alkylcarbonyl group may be substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group) ) Represents a trialkylsilyl group consisting of three identical or different alkyl groups.) (E) -1-Chloro-3,3,3-trifluoropropene and terminal acetylenes represented by the formula [2]

(E) -5,5,5-trifluoro-3-penten-1-ynes represented by the formula [5] by reacting with a palladium catalyst in the presence of a basic substance.

How to manufacture.
(In the formula, R ³ is a hydrogen atom, a phenyl group (wherein part or all of the hydrogen atoms of the phenyl group may be substituted with a halogen (fluorine, chlorine, bromine, iodine), an amino group or a hydroxyl group) ), A linear, branched or cyclic alkyl group having 1 to 6 carbon atoms (wherein some or all of the hydrogen atoms in the alkyl group are substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group) A straight chain, branched chain or aryl group having 1 to 6 carbon atoms (wherein some or all of the hydrogen atoms of the aryl group are halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group) A linear, branched or cyclic alkylcarbonyl group having 1 to 6 carbon atoms (wherein part of the hydrogen atom of the alkylcarbonyl group or Halogen is Te (fluorine, chlorine, bromine, iodine), may be substituted with an amino group or hydroxyl group), represents a trialkylsilyl group of the same or different three alkyl groups.) A process for producing (E) -5,5,5-trifluoro-3-penten-1-yne, comprising the following two steps.
First step: (E) -1-chloro-3,3,3-trifluoropropene and terminal acetylenes represented by the formula [2a]

Is reacted with a palladium catalyst in the presence of a basic substance to give (E) -5,5,5-trifluoro-3-penten-1-ynes (substituted acetylene) represented by the formula [5a]

Obtaining.
Second step: (E) -5,5,5-trifluoro-3-penten-1-yne (substituted acetylene) represented by the formula [5a] obtained in the first step is used as a basic substance. A step of reacting to produce (E) -5,5,5-trifluoro-3-penten-1-yne.
(Wherein R ^3a represents a phenyl group (wherein part or all of the hydrogen atoms of the phenyl group may be substituted with a halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group), carbon A linear, branched or cyclic alkyl group of 1 to 6 (wherein some or all of the hydrogen atoms of the alkyl group are substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group; Or a straight chain, branched chain or aryl group having 1 to 6 carbon atoms (wherein part or all of the hydrogen atoms of the aryl group are substituted with halogen (fluorine, chlorine, bromine, iodine), amino group or hydroxyl group) A straight-chain, branched-chain or cyclic alkylcarbonyl group having 1 to 6 carbon atoms (wherein some or all of the hydrogen atoms of the alkylcarbonyl group are halo) Emissions represents (fluorine, chlorine, bromine, iodine), may be substituted with an amino group or hydroxyl group), a trialkylsilyl group of the same or different three alkyl groups.) The 1-chloro-2-trifluoromethyl-ethylenes represented by the formula [1] and the terminal acetylenes represented by the formula [2] or the formula [2a] according to any one of claims 1 to 4. To obtain 5,5,5-trifluoro-3-penten-1-ynes represented by the formula [3] or [3a], or (E) -1-chloro-3, (E) -5,5,5 represented by formula [5] or formula [5a] by reacting 3,3-trifluoropropene with a terminal acetylene represented by formula [2] or formula [2a] The method according to any one of claims 1 to 4, wherein the basic substance used in obtaining 5-trifluoro-3-penten-1-ynes is an organic amine. The 1-chloro-2-trifluoromethyl-ethylene represented by the formula [1] and the terminal acetylene represented by the formula [2] or the formula [2a] according to any one of claims 1 to 5. To obtain 5,5,5-trifluoro-3-penten-1-ynes represented by the formula [3] or [3a], or (E) -1-chloro-3, (E) -5,5,5 represented by the formula [5] or the formula [5a] by reacting 3,3-trifluoropropene with a terminal acetylene represented by the formula [2] or the formula [2a]. The method according to any one of claims 1 to 5, wherein a trivalent phosphorus compound is further allowed to coexist in obtaining 5-trifluoro-3-penten-1-ynes. (E) -7,7,7-trifluoro-2-methyl-5-hepten-3-in-2-ol. Trimethyl-((E) -5,5,5-trifluoro-3-penten-1-ynyl) silane. (E) -6,6,6-trifluoro-4-hexen-2-in-1-ol. ((E) -5,5,5-trifluoro-3-penten-1-ynyl) benzene. (E) -5,5,5-trifluoro-3-penten-1-yne.