JPS63222694A - Fluoroalkylation by enzyme - Google Patents

Abstract

PURPOSE:To efficiently obtain fluoroalkylated acetylenes useful as industrial raw materials, etc., by reacting a specific perhaloalkane with an acetylene derivative in the presence of an enzyme. CONSTITUTION:One equiv. perhaloalkane expressed by formula I (X and Y are same or different halogen; Z is Br or I; n is 0 or >=1) (e.g. perfluoroalkyl iodide) and 1-100 equiv. acetylene derivative expressed by formula II [R1 and R2 are same or different H, (ar)alkyl or aryl] are added to a solvent containing water. An enzyme having metallic ions as a prosthetic group (e.g. urease having Ni) is then added to the solvent and, as necessary, a surfactant is added and reacted at 0-55 deg.C to form perfluoroalkylethylenes expressed by formula III.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a fluoroalkylation process for introducing fluoroalkyl groups into acetylenes.

The reaction of introducing fluoroalkyl groups into acetylenes has been studied for a long time. Initially, light irradiation, heating, and radical initiators were used, but recently, methods for activating perhaloalkanes using electrolysis and various metal reactants have been developed to improve selectivity. (Journal of Kakuki Synthesis Association, Vol. 42, 775 (1984)), L/ However, these methods require reaction conditions such as organic *wk, metal, temperature, pressure, etc., which are undesirable from the viewpoint of the production process. shall be.

In response, the present inventor has developed a method for activating perhaloalkanes using an enzymatic reaction, which has not been studied so far! After much research, we were able to develop a novel fluoroalkylation that had not been seen using conventional chemical methods. That is, the present invention provides a novel method for fluoroalkylating acetylene, which is characterized by reacting a perhaloalkane having at least one fluorine atom and at least one bromine or iodine atom with an acetylene derivative in the presence of an enzyme. This is what we provide.

According to the method of the present invention, a perhaloalkane represented by the above formula [11] and a R1-C=iC-R2 [2] cetylenes represented by the following formula [2] are combined by the action of an appropriate enzyme PeHCX represented by the following formula [3]
It was discovered for the first time that the Y (C+iF 21101) fluoroalkylethylene term could be efficiently obtained in one step under mild conditions.

As the perhaloalkane in the present invention, a compound represented by the following formula [■] can be used.

CnF2n+1-C-Y (1) Where, X and Y are the same or different halogen atom Z is a bromine atom or an iodine atom n is an integer of 0 or 1 or more Among the compounds represented by formula [1], preferred compounds are X
and Y are both fluorine atoms, or a compound in which one is a fluorine atom and the other is a halogen atom, a bromine atom, or a fluorine atom. The former can introduce useful perfluoroalkyl groups into acetylene, while the latter can introduce fluoroalkyl groups with active halogen atoms (i.e., odorant atoms or iodine atoms) that can be later attached to various functional or organic groups. It is useful for introducing groups. ・N in formula [11 is usually suitably 30 or less,
In particular, 16 or less is preferable.

Examples of acetylene derivatives include acetylene having at least one unsaturated triple bond and derivatives thereof (for example, acetylene having an inert functional group), and acetylene having one unsaturated triple bond is particularly preferred. , compounds represented by the following formula [2] are preferred.

R1-CmiC-R2C2 In formula [2], R1 and R2 may be different or the same, and represent a hydrogen atom, an alkyl group, an aryl group, an aralkyl group, etc.

The alkyl group may be a cycloalkyl group as well as a linear or branched alkyl group, and the aryl group or aralkyl group may have an aromatic nucleus substituent such as an alkyl group.

The number of carbon atoms in the acetylenes is not particularly limited, but it is preferably about 20 or less, particularly 15 or less.It depends on the type of target product, but products having a fluoroalkyl group at the end are highly useful, and by-products Acetylenes in which one of R1 and R2 is a hydrogen atom are preferred for reasons such as a decrease in the number of hydrogen atoms.

The enzyme used in the present invention is particularly preferably an enzyme having a metal ion as a prosthetic group.

Such W# capsules include urease containing nickel,
Enzymes such as catalase, peroxidase, hemoglobin, and myoglobin having protoheme can be mentioned, and urease and catalase are particularly preferred.

The reaction is carried out by adding 1 to 100 equivalents of the acetylene derivative to 1 equivalent of perfluoroalkyl iodide, preferably 1 to 5 equivalents to improve the selectivity, adding the enzyme, and stirring or stirring in water or a solvent containing water. This is done by shaking.

A surfactant may be added if necessary, and it is also possible to use an immobilized enzyme.

The reaction temperature is suitably 0 to 55°C, particularly preferably 20 to 40°C.

There is no need to particularly control the reaction pH, but an appropriate buffer α
may also be used.

As a result of the reaction, for example, a product represented by the following formula [3] is produced from the perhaloalkane represented by the above formula [1] and the acetylene represented by the above formula [2].

When the acetylenes have a terminal unsaturated triple bond, the fluoroalkyl group is usually attached to the terminal carbon atom, and only olefins with trans stereochemistry are produced. That is, in the formula [3],
A product is obtained in which R2 is a hydrogen atom.

The present invention will be explained in more detail below with reference to Examples.
The present invention is not limited to these examples.

Example 1-15 A series of perhaloalkanes shown in Table 1 (10 m, mol
), acetylene derivative (catalase or urease for 20 mmol, both manufactured by Nagase Sangyo, 10 rng
) was added and stirred for 1 to 4 weeks in a pH 8 phosphate buffer, the fluoroalkylated products shown in the table were obtained.

Table 1

Claims (1)

[Claims] 1. Acetylene fluoroalkylation method 2, which comprises reacting a perhaloalkane having at least one fluorine atom and at least one bromine or iodine atom with an acetylene derivative in the presence of an enzyme. , Production method 3 according to claim 1, characterized in that an enzyme having a metal ion as a prosthetic group is used as oxygen, and the perhaloalkane is a compound represented by the following formula [1] Manufacturing method described in claim 1 ▲ Numerical formulas, chemical formulas, tables, etc. are included ▼ [1] However, X and Y are the same or different halogen atoms Z is a bromine atom or an iodine atom n is an integer of 0 or 1 or more 4, The manufacturing method according to claim 1, characterized in that acetylenes are used in an excess amount relative to perhaloalkanes.