JP2002363110A - Method for producing fluorinated organic compound and fluorinated reagent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve regioselectivity to carbon-carbon double bond in addition reaction of iodine fluoride. SOLUTION: This method for producing a fluorinated organic compound is characterized by adding the iodine fluoride(IF) with reacting IF5 , iodine and an organic base to the carbon-carbon double bond of the organic compound under a condition of stronger acidity.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a fluorinated organic compound and a reagent for fluorinating an organic compound having a double bond.

[0002]

2. Description of the Related Art The addition reaction of iodine fluoride to a carbon-carbon double bond is a very useful reaction because a fluorine atom and an iodine atom can be simultaneously introduced into a molecule in a single reaction. As a reaction reagent for adding iodine fluoride to a carbon-carbon double bond, an iodine atom source reagent and a fluorine atom source reagent are often used in combination, for example, iodine and fluorine, iodine and (HF) _x -Pyridine, I (C ₅ H ₅
N) ₂ BF ₄ and HBF ₄ , I (collidine) ₂ BF ₄ , N-iodosuccinimide and HF, N-iodosuccinimide and (HF) _x -pyridine, N-iodosuccinimide and Et ₃ N-3HF, N-iodo Succinimide and (C ₄ H ₉ ) ₄ NHF ₂ , N-iodosuccinimide and C
There are many reports such as HClFCF ₂ N (C ₂ H ₅ ) ₂ , N-iodosuccinimide and NH ₄ HF ₂ and aluminum fluoride, iodine and XeF ₂ , iodine and silver fluoride, iodine and lead tetraacetate and HF ( M. Hudli
cky, Chemistry of Organic Fluorine Compounds, 1976,
Ellis Horwood .: M. Hudlicky and AE Pavlath, C
hemistryof Organic Fluorine Compounds II, 1995, AC
S Monograph 187). However, the method using iodine and fluorine has a severe control of the reactivity of fluorine.
A low temperature condition of 8 ° C is required, and I (C ₅ H ₅ N) ₂ BF ₄ and HB
The method using F ₄ , I (collidine) ₂ BF ₄ is the reagent (I (C ₅ H ₅ N) ₂ B
Preparation of F ₄ , I (collidine) ₂ BF ₄ ) is complicated, and N-iodosuccinimide and HF, N-iodosuccinimide and (HF) _x
- pyridine, N- iodosuccinimide and Et ₃ N-3HF, N- iodosuccinimide and _{(C 4 H 9) 4 NHF} 2, N- iodosuccinimide and _{CHClFCF 2 N (C 2 H 5} ) 2, and N- iodosuccinimide
The method using NH ₄ HF ₂ and aluminum fluoride, iodine and XeF ₂ , iodine and silver fluoride can be performed using reagents (N-iodosuccinimide, Xe
F ₂ , silver fluoride) is expensive, and the method using iodine, lead tetraacetate and HF has many problems as an industrial synthesis method, such as the necessity of treating a waste liquid containing lead after the reaction. Iodine and (HF) _x
-Pyridine is inexpensive and easy to handle, but the yield is low, leaving the problem that stoichiometric addition of expensive silver nitrate is necessary to improve the yield (GA Olah, JT Welch.
YD Vankar, M. Nojima, I. Kerekes and JA Ola
h, J. Org. Chem., 1979, 44, 3872.).

The inventors have reported that the addition reaction of iodine fluoride to a carbon-carbon double bond proceeds in the presence of IF ₅ , iodine and Et ₃ N-3HF (Fukuhara, Shimokawa) , Yoneda, Proceedings of the 24th Fluorochemistry Symposium O-15, 200
1). However, this method has a problem to be solved in that regioisomers having different addition directions of iodine fluoride are produced as by-products and the yield of the target compound is reduced.

[0004]

The present invention relates to a simple and efficient addition of iodine fluoride to a carbon-carbon double bond of an organic compound.

[0005]

Means for Solving the Problems The present inventors have conducted intensive studies in view of the above-mentioned problems, and as a result, have found that reagents such as IF ₅ , iodine, an organic base, and a nitrogen atom of an organic base which are inexpensive and can be supplied in large quantities. It has been found that the coexistence of HF in an amount of three times or more with respect to one allows the addition reaction of iodine fluoride to the carbon-carbon double bond to proceed efficiently and regioselectivity to be remarkably improved.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention comprises reacting IF ₅ , iodine and an organic base with a compound having a carbon-carbon double bond under stronger acidic conditions, and adding IF to the carbon-carbon double bond, It is characterized in that it is added in such a manner that only isomers are formed.

[0007] As used herein, "stronger acidic conditions" means that an acid is contained in an amount larger than that which forms a stable complex with an organic base. For example, when 1 mol of triethylamine is used as a base, triethylamine generally forms a complex with 3 times mol of HF (J. Fluorine).
Chem., R. Franz, 1980, 15, 423), more than 3 moles of HF,
Preferably, about 4 to 10 moles are used.

In the present invention, the compound having a carbon-carbon double bond is a compound containing an alkenyl group represented by the general formula R ¹ R ² C ＝ CH ₂ in the molecule.
[Wherein, R ¹ and R ² are the same or different and each may have a hydrogen atom, an alkyl group which may have a substituent, an aralkyl group which may have a substituent, or a substituent. Aryl group, cycloalkyl group which may have a substituent, heterocycloalkyl group which may have a substituent, heterocyclic group which may have a substituent, alkoxy group which may have a substituent Is shown. R ¹ and R ² may combine with each other to form a cyclic structure. ].

The compound having a carbon-carbon double bond of the present invention may have two or more double bonds.

As the alkyl group, methyl, ethyl, n
-Propyl, isopropyl, n-butyl, isobutyl,
sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, octadecyl, nonadecyl, eicosyl, henicosyl, docosyl, tricosyl, tetracosyl, pentacosyl, etc. C _1- having a chain or a branch
C ₂₅ alkyl group, preferably methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, sec
C ₁ -C ₂ having a linear or branched such as -butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, octadecyl, nonadecyl, eicosyl and the like. ₀ alkyl groups.

The aralkyl group includes benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl,
- phenyl hexyl, 7-phenyl-heptyl, 8-phenyl-octyl, 9-phenyl-nonyl, include C ₇ -C ₂₀ aralkyl groups, such as 10-phenyl-decyl.

Examples of the aryl group include a phenyl group, a naphthyl group, an anthryl group and a phenanthryl group.

The cycloalkyl group includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
Dimethylcyclohexyl, cycloheptyl, C ₃ -C ₂₀ cycloalkyl group such as cyclooctyl, preferably C ₃
-C ₈ cycloalkyl group.

Examples of the heterocycloalkyl group include a heterocycloalkyl group containing an oxygen atom and a sulfur atom such as tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, dioxanyl, dithianyl, oxathiolanyl, and thioxanyl.

The heterocyclic group includes a heterocyclic group containing an oxygen atom and a sulfur atom such as furyl, thienyl, benzofuryl and benzothienyl.

Examples of the alkoxy group include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,
Isobutoxy, sec- butoxy, tert- butoxy, pentyloxy, and a C ₁ -C ₂₀ alkoxy group having a straight-chain or branched, such as hexyloxy.

An alkyl group having a substituent, an aralkyl group having a substituent, an aryl group having a substituent, a cycloalkyl group having a substituent, a heterocycloalkyl group having a substituent, a heterocyclic group having a substituent, As a substituent of the alkoxy group having a group, a halogen atom, C ₁ to
C ₂₀ alkyl, C ₁ -C ₂₀ alkoxy, C ₁ -C ₂₀ haloalkyl, C ₁ -C ₂₀ haloalkoxy, C ₁ -C ₂₀ alkylthio, C ₁ -C ₂₀ haloalkylthio, cyano, nitro,
Examples of the alkyl group having a halogen atom include an alkyl group having a halogen atom, particularly a fluorine atom, in which part or all of the alkyl group is substituted with a halogen atom.

Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

Examples of the organic base used in the present invention include those commonly used. Examples thereof include aliphatic amines (primary amines, secondary amines, tertiary amines) and alicyclic amines (primary amines). Organic bases such as secondary amines, tertiary amines), aromatic amines (primary amines, secondary amines, tertiary amines), and heterocyclic amines; , Methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine, cyclohexylamine, ethylenediamine, and the like.Examples of the aliphatic secondary amine include dimethylamine,
Diethylamine, dipropylamine, dibutylamine,
Dipentylamine, dihexylamine, dicyclohexylamine and the like, and as the aliphatic tertiary amine,
Trimethylamine, triethylamine, tributylamine, diisopropylethylamine, N, N, N ', N'-tetramethylethylenediamine, and the like; examples of alicyclic secondary amines include piperidine, piperazine, pyrrolidine, and morpholine; As the cyclic tertiary amine, N-
Methylpiperazine, N-methylpyrrolidine, 5-diazabicyclo [4.3.0] nonane-5-ene, 1,4-diazabicyclo [2.
2.2] octane; aromatic amines include aniline, methylaniline, dimethylaniline, N, N-dimethylaniline, haloaniline, nitroaniline, and the like; heterocyclic amines include pyridine, pyrimidine,
Examples thereof include pyrazine, quinoline, imidazole and the like, and further include a polymer-carrying amine compound such as polyallylamine and polyvinylpyridine; or a mixture thereof.

The process of the present invention uses 0.2 to 20 moles, preferably 0.3 to ₅ moles, of IF5 per mole of a compound having a carbon-carbon double bond, and Can be selected in the range of catalyst amount to excess amount,
Preferably 0.1 mol per mol of the compound to be fluorinated.
Up to 50 mol can be used. The amount of HF used can be selected in the range of a large excess from the amount of the catalyst, but in order to make the reaction system more strongly acidic, more than three times the amount of one nitrogen atom of the organic base to be added. Is preferably used, and more preferably about 4 to 20 times.

Generally, triethylamine is three times the molar amount of HF
And a complex (J. Fluorine Chem., R. Franz, 1980,
15, 423), and more HF is added, the acidity is further increased. Addition of iodine fluoride to 1-dodecene, which is a compound having a carbon-carbon double bond, is via a carbocation (A), which is an intermediate, and is a reactive species (B ) And (C) become equilibrium and react with each other. From (B), (D) becomes (C)
From (E) is considered to be generated.

[0022]

Embedded image

As the acidity of the reaction system increases, the carbocation, which is a reaction intermediate, is further stabilized, and its life is extended. As a result, the carbocation (B) stabilized by an electron-donating substituent is equilibrated. Is expected to tilt. In fact, in Example 1, by adding Et ₃ N-5HF salt, the formation ratio of compounds D and E became 98: 2, and Comparative Example 1
In the case of (D: E = 81: 19), the generation ratio was dramatically improved. This is to make the reaction system acidic,
It is understood that the carbocation (B) which is more energetically stable is generated due to the equilibrium of the carbocation as described above, and as a result, the 2-fluoro form was preferentially obtained. Thus, when the terminal of the compound is a double bond, it is preferable to make the inside of the reaction system more acidic in order to improve the regioselectivity of the product. It is preferable to add more than three times the amount of HF.

The reaction temperature is from -70 ° C to 200 ° C, preferably from -20 ° C to 100 ° C.
The desired product can be obtained.

The reaction solvent may or may not be used,
Preferably used. As the reaction solvent, pentane,
Aliphatic solvents such as hexane, heptane, cyclohexane, petroleum ether, dichloromethane, dichloroethane, chloroform, fluorotrichloromethane, 1,1,2-trichlorotrifluoroethane, 2-chloro-1,2-dibromo-1,1,
2-trifluoroethane, 1,2-dibromohexafluoropropane, 1,2-dibromotetrafluoroethane, 1,1-difluorotetrachloroethane, 1,2-difluorotetrachloroethane, heptafluoro-2,3,3-trichloro butane,
1,1,1,3-tetrachlorotetrafluoropropane, 1,1,1-
Halogenated aliphatic solvents such as trichloropentafluoropropane, 1,1,1-trichlorotrifluoroethane, polychlorotrifluoroethylene, methyl formate, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, methyl propionate, γ- Butyrolactone, ester solvents such as propion carbonate, acetonitrile, nitrile solvents such as propionitrile, benzene, chlorobenzene, toluene, dichlorobenzene, fluorobenzene,
Aromatic solvents such as nitrobenzene, diethyl ether,
Ether solvents such as dipropyl ether and tetrahydrofuran, N, N-dimethylformamide, dimethylsulfoxide, water, nitromethane, N, N-diethylformamide, N, N-dimethylacetamide, 1-methyl-
Examples thereof include 2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone, tetramethylurea, 1,3-dimethylpropyleneurea, and hexamethylphosphoramide, which are used alone or as a mixture of any two or more kinds. .

[0026]

According to the present invention, using the IF ₅ suitable for industrial use in inexpensive, can be introduced fluoride iodine compounds having a variety of double bonds. In addition, the coexistence of HF exceeding 3 equivalents with respect to the added organic base significantly improves the regioselectivity of hydrogen fluoride addition.

[0027]

EXAMPLES Hereinafter, the present invention will be described with reference to Examples and Comparative Examples.
This will be described in more detail.

[0028]

【table 1】

Example 1 IF was placed in a PFA container (30 ml)._Five/ Et_ThreeN-3
HF 460 mg (1.2 mmol), I_Two 127 mg (0.5 mmol), CH _TwoCl_Two 8
ml, Et_ThreeN-5HF 2 ml and 1-dodecene 189 ml (1.0 mmol)
And the reaction vessel was heated in a 40 ° C. oil bath for 28 hours. reaction
After completion, quench with about 20 ml of ice water and extract with ether
And saturated aqueous sodium bicarbonate and 10% hypo
In addition, neutralization and decomposition of oxidizing substances were performed. ether
The solution was dried over potassium carbonate and obtained by evaporation of the solvent
The crude product is subjected to column chromatography (developing solvent;
Sun), and purify 2-fluoro-1-iodo-dodecane to 83
%, 1-fluoro-2-iodo-dodecane at 2%. Compound Data: 2-Fluoro-1-iodo-dodecane:¹ H-NMR (CDCl_Three) δ0.88 (3H, t, J = 7.1 Hz), 1.27-1.46
(16H, m), 1.2-1.92 (2H, m), 4.13-4.22 (2H, dm, J = 20.0
 Hz), 4.45 (1H, dm, J = 47.6Hz);¹⁹ F-NMR (CDCl_Three) δ-171.2- -171.5 (1F, m); IR (neat) 2925, 2854, 1465, 1414, 1338, 1187, 991,
 721, 637. 1-Fluoro-2-iodo-dodecane:¹ H-NMR (CDCl_Three) δ0.88 (3H, t, J = 7.1 Hz), 1.26-1.46
(16H, m), 1.67-1.78 (2H, m), 3.31 (1H, m), 4.28-4.69
(2H, m);¹⁹ F-NMR (CDCl_Three) δ-198.4 (1F, dt, J = 13.4 Hz, J = 47.6
 [Comparative Example 1] IF in a container made of PFA (30 ml)_Five/ Et_ThreeN-3HF 460 mg (1.
2 mmol), I_Two 127 mg (0.5 mmol), CH _TwoCl_Two 8ml, Et_ThreeN-3HF
 Add 2 ml and 189 ml (1.0 mmol) of 1-dodecene and react.
The vessel was heated in a 40 ° C. oil bath for 3 hours. After the reaction is completed, about 20
Quench with ml of ice water, extract with ether and add saturated bicarbonate
Neutralize by adding sodium aqueous solution and 10% hypo aqueous solution.
And unreacted oxidizing substances were decomposed. Ether solution with charcoal
Crude product obtained by drying over potassium phosphate and evaporating the solvent
To column chromatography (developing solvent: hexane)
More purified, 65% 2-fluoro-1-iodo-dodecane, 1-fluo
ro-2-iodo-dodecane was obtained at 15%.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Koji Oishi 3rd Miyukigaoka, Tsukuba, Ibaraki Daikin Industries, Ltd. F-term (reference) 4H006 AA02 AA03 AB81 AC30 BA37 BA51 BC17 BC32 BE53 EA02 4H039 CA51 CA54 CF10

Claims (6)

[Claims] 1. The method according to claim 1, wherein IF is added to a carbon-carbon double bond of the organic compound.
_{5. A} process for producing a fluorinated organic compound, which comprises adding iodine fluoride (IF) under stronger acidic conditions in the presence of iodine and an organic base. 2. The method according to claim 1, wherein the carbon-carbon double bond of the organic compound is
₅ , iodine, organic base, and nitrogen atom 1 of organic base
The method for producing a fluorinated organic compound according to claim 1, wherein iodine fluoride (IF) is added in the presence of HF that is more than three times the amount of HF. 3. The method for producing a fluorinated organic compound according to claim 1, wherein the organic base is triethylamine. 4. The method for producing a fluorinated organic compound according to claim 1, wherein iodine fluoride is added to a terminal double bond of the organic compound. 5. A fluorination reagent for an organic compound for adding iodine fluoride to an organic compound having a double bond, wherein
A reagent comprising F ₅ , iodine, an organic base, and HF in an amount greater than 3 times the amount of one nitrogen atom of the organic base. 6. The fluorination reagent for an organic compound according to claim 5, wherein the organic base is triethylamine.