WO2015166961A1

WO2015166961A1 - 1,1,2-tribromoethane production method

Info

Publication number: WO2015166961A1
Application number: PCT/JP2015/062878
Authority: WO
Inventors: 淳白井; 大塚　達也; 洋介岸川; 智仁濱田
Original assignee: ダイキン工業株式会社
Priority date: 2014-04-28
Filing date: 2015-04-28
Publication date: 2015-11-05
Also published as: WO2015166962A1

Abstract

The purpose of the present invention is to provide a low-cost and high-yield production method for 1,1,2-tribromoethane. The present invention provides a 1,1,2-tribromoethane production method that includes a step (A) wherein 1,1,2-tribromoethane is obtained by brominating a 1,1,2-trihaloethane that is represented by general formula (1). [In the formula, X¹, X², and X³ represent a chlorine atom or a bromine atom, provided that at least one of X¹, X², and X³ is a chlorine atom.]

Description

Process for producing 1,1,2-tribromoethane

The present invention relates to a method for producing 1,1,2-tribromoethane.

1,1-Dibromoethylene is a synthetic intermediate for pharmaceuticals (for example, antibiotics), a synthetic intermediate for optical fiber sheath materials, a synthetic intermediate for coating materials, a synthetic intermediate for semiconductor resist materials, and a highly functional compound. This compound is useful as an intermediate for the synthesis of molecular monomers.
Conventionally, it is known that 1,1-dibromoethylene is obtained by dehydrobromination of 1,1,2-tribromoethane (Patent Document 1).
Here, it is known that 1,1,2-tribromoethane, which is a raw material of the production method disclosed in Patent Document 1, is obtained by a bromine addition reaction of vinyl bromide (Non-Patent Document 1). ).
Patent Documents 2 to 4 each disclose a method for producing an alkyl bromide from alkyl chloride using hydrogen bromide or aluminum and bromine.

Japanese Patent Laid-Open No. 50-52006 US Pat. No. 1,891,415 U.S. Pat. No. 2,120,675 US Pat. No. 2,057,964

In the production method described in Non-Patent Document 1, vinyl bromide, which is a raw material, must be produced by bromination of ethylene followed by dehydrobromination, so that the number of steps and waste are large. For industrial use, it is disadvantageous from the viewpoint of manufacturing cost and the like.
Further, when alkyl chloride was used as a raw material as in the production methods described in Patent Documents 2 to 4, according to the study by the present inventors, the yield and purity of the target alkyl bromide were low.
Accordingly, an object of the present invention is to provide a method for producing 1,1,2-tribromoethane which is low in cost and high in yield.
Another object of the present invention is to provide a method for producing 1,1-dibromoethylene which is low in cost and high in yield.

As a result of intensive studies, the present inventors have found that the formula (1):

[Where:
X ¹ , X ² , and X ³ represent a chlorine atom or a bromine atom.
However, at least one of X ¹ , X ² , and X ³ is a chlorine atom. ]
By further converting the chlorine atom of 1,1,2-trihaloethane represented by the following formula to bromine atom, we found that 1,1,2-tribromoethane can be produced at low cost and high yield. As a result, the present invention has been completed.

The present invention includes the following aspects.

Item 1.
A method for producing 1,1,2-tribromoethane having the formula (1):

[Where:
X ¹ , X ² , and X ³ represent a chlorine atom or a bromine atom.
However, at least one of X ¹ , X ² , and X ³ is a chlorine atom. ]
Represented by
A production method comprising a step A in which 1,1,2-trihaloethane is brominated to obtain 1,1,2-tribromoethane.
Item 2.
Item 2. The production method according to Item 1, wherein the 1,1,2-trihaloethane represented by the formula (1) is 1,2-dibromo-1-chloroethane or 1,1,2-trichloroethane.
Item 3.
Item 3. The production method according to Item 1 or 2, wherein in step A, 1,1,2-trihaloethane represented by the formula (1) is reacted with aluminum and bromine to obtain 1,1,2-tribromoethane.
Item 4.
In step A, 1,1,2-trihaloethane represented by the formula (1) is reacted with an aluminum halide having one or more bromine atoms to obtain 1,1,2-tribromoethane 4. The production method according to any one of 3 above.
Item 5.
Item 5. The method according to Item 4, wherein the aluminum halide having one or more bromine atoms is aluminum bromide.
Item 6.
Item 6. The production method according to any one of Items 1 to 5, wherein the reaction temperature in Step A is in the range of −78 ° C. to 20 ° C.
Item 7.
Item 7. The production method according to any one of Items 1 to 6, wherein Step A is carried out in the presence of an alkyl halide compound as a reaction solvent.
Item 8.
A method for producing 1,1-dibromoethylene, wherein 1,1,2-tribromoethane obtained by the production method according to any one of Items 1 to 7 is dehydrobrominated using a base. , A production method comprising a step B of obtaining 1,1-dibromoethylene.
Item 9.
Item 9. The production method according to Item 8, wherein Step B is carried out in the presence of a water-soluble organic solvent as a reaction solvent or a mixed solvent of a water-soluble organic solvent and water.
Item 10.
Item 9. The production method according to Item 8, wherein Step B is carried out using a phase transfer catalyst in the presence of water and in the absence of a water-soluble organic solvent.
Item 11.
Step B is one or more amine compounds, and (1) a compound having a hydroxyl group,
(2) a compound having a sulfide bond,
Items 8 to 10 are carried out in the presence of one or more compounds selected from the group consisting of (3) a compound having a thiophenolic or thiol sulfur atom, and (4) a sulfite compound (5) a nitrite compound. 11. The production method according to any one of 10 above.

The present invention provides a method for producing 1,1,2-tribromoethane that is low in cost and high in yield.
The present invention also provides a method for producing 1,1-dibromoethylene that is low in cost and high in yield.

Method for Producing 1,1,2-Tribromoethane The method for producing 1,1,2-tribromoethane according to the present invention comprises the steps of brominating 1,1,2-trihaloethane represented by the formula (1) and Step A to obtain 1,2-tribromoethane.
The 1,1,2-trihaloethane represented by the formula (1) used in Step A can be produced by a known method or a method analogous thereto. 1,1,2-trihaloethane is also commercially available.
The 1,1,2-trihaloethane represented by the formula (1) used in Step A is preferably 1,2-dibromo-1-chloroethane or 1,1,2-trichloroethane, for example. As the 1,1,2-trihaloethane represented by the formula (1), a mixture of 1,2-dibromo-1-chloroethane and 1,1,2-trichloroethane may be used.
Among these, 1,2-dibromo-1-chloroethane is particularly preferable because the production of by-products is highly suppressed.
Of the 1,1,2-trihaloethane represented by the formula (1), 1,2-dibromo-1-chloroethane is specifically preferred for a method including a step of adding bromine to vinyl chloride, for example. Can be manufactured. This method is advantageous because 1,2-dibromo-1-chloroethane can be produced using vinyl chloride, which is easily available and inexpensive. The method for producing 1,2-dibromo-1-chloroethane will be described in detail later.

In a preferred embodiment of the present invention, the reaction of Step A (that is, bromination of 1,1,2-trihaloethane represented by the formula (1)) is preferably represented by the formula (1). This can be done by reacting 1,1,2-trihaloethane with aluminum and bromine. That is, in this embodiment, in step A, 1,1,2-trihaloethane represented by the formula (1) is reacted with aluminum and bromine to obtain 1,1,2-tribromoethane.
The form of aluminum is not particularly limited, and can be used in Step A in a normal form such as powder, granule, or foil.
The amount of aluminum is preferably in the range of 0.1 equivalents to 5 equivalents, more preferably 0.1 equivalents to 3 equivalents, relative to the 1,1,2-trihaloethane represented by the formula (1). And more preferably in the range of 0.2 to 2 equivalents.
Bromine may be added to the reaction system of Step A together with the solvent described later (for example, as bromine dissolved in the solvent described later).
The amount of bromine is preferably in the range of 0.1 equivalents to 5 equivalents, more preferably 0.1 equivalents to 3 equivalents, relative to the 1,1,2-trihaloethane represented by the formula (1). And more preferably within the range of 0.1 to 2 equivalents.

In another preferred embodiment of the present invention, the reaction of Step A (that is, bromination of 1,1,2-trihaloethane represented by the above formula (1)) is also preferably represented by the above formula (1). The 1,1,2-trihaloethane represented by can be reacted with an aluminum halide having one or more bromine atoms. That is, in this embodiment, in Step A, 1,1,2-trihaloethane represented by the formula (1) is reacted with an aluminum halide having one or more bromine atoms to produce 1,1,2-tribromo. Get ethane. Examples of the aluminum halide having one or more bromine atoms include AlBrCl ₂ , AlBr ₂ Cl, AlBrF ₂ , AlBr ₂ F, AlBrClF, and AlBr ₃ (aluminum bromide). An aluminum halide may be used individually by 1 type, or may be used in combination of 2 or more type. The aluminum halide having one or more bromine atoms is preferably AlBrCl ₂ , AlBr ₂ Cl, or AlBr ₃ , and more preferably AlBr ₃ .
The amount of the aluminum halide having one or more bromine atoms varies depending on the type of the aluminum halide, but is preferably 0.1% relative to the 1,1,2-trihaloethane represented by the formula (1). It is in the range of 1 equivalent to 5 equivalents, more preferably in the range of 0.1 equivalents to 3 equivalents, and still more preferably in the range of 0.2 equivalents to 2 equivalents.

A suitable reaction temperature in Step A may vary depending on the raw material compound in Step A (that is, 1,1,2-trihaloethane represented by the formula (1)), but in one embodiment of the present invention, in Step A, The upper limit of the reaction temperature is preferably 50 ° C., more preferably 20 ° C .; the lower limit of the reaction temperature in Step A is preferably −78 ° C., more preferably −60 ° C., still more preferably − 50 ° C, even more preferably -40 ° C; and the reaction temperature of step A is preferably in the range of -78 ° C to 50 ° C, more preferably in the range of -60 ° C to 20 ° C, further Preferably, it is in the range of −50 ° C. to 20 ° C., or −50 ° C. to −20 ° C., and more preferably in the range of −40 ° C. to 20 ° C., or −40 ° C. to −20 ° C.
As for the suitable reaction temperature of Step A, in another embodiment, the upper limit of the reaction temperature of Step A is preferably 20 ° C., more preferably 0 ° C .; the lower limit of the reaction temperature of Step A is preferably Is −78 ° C., more preferably −60 ° C., still more preferably −50 ° C., even more preferably −40 ° C .; and the reaction temperature in Step A is preferably −78 ° C. to 20 ° C. Within a range of −50 ° C. to 0 ° C., more preferably within a range of −50 ° C. to −10 ° C., and even more preferably within a range of −40 ° C. to −10 ° C. .
When the starting compound of Step A is 1,2-dibromo-1-chloroethane, the upper limit of the reaction temperature is preferably 20 ° C., more preferably 10 ° C., and even more preferably 0 ° C .; The lower limit is preferably −78 ° C., more preferably −60 ° C., still more preferably −40 ° C .; and the reaction temperature in step A is preferably in the range of −78 ° C. to 20 ° C., more Preferably, it is in the range of −60 ° C. to 10 ° C., more preferably in the range of −40 ° C. to 0 ° C.
When the raw material compound of step A is 1,1,2-trichloroethane, the upper limit of the reaction temperature is preferably 20 ° C., more preferably 10 ° C., still more preferably 5 ° C .; the lower limit of the reaction temperature is Preferably −78 ° C., more preferably −50 ° C., still more preferably −30 ° C .; and the reaction temperature in step A is preferably within the range of −78 ° C. to 20 ° C., more preferably − It is in the range of 50 ° C. to 10 ° C., more preferably in the range of −30 ° C. to 5 ° C.
If the reaction temperature in step A is too high, the yield of 1,1,2-tribromoethane tends to decrease.
However, when the reaction temperature in step A is low, it is difficult to reduce the reaction temperature in this way, which is disadvantageous in terms of cost.
Therefore, when the yield of 1,1,2-tribromoethane is sufficient, the reaction temperature in step A is usually more preferable.

The reaction time of step A is usually in the range of 0.5 to 10 hours.

Step A can be carried out in the presence or absence of a reaction solvent.
Step A is preferably carried out in the presence of a reaction solvent from the viewpoint of high reliability of reaction progress.
When step A is carried out in the presence of a reaction solvent, the reaction solvent is preferably an alkyl halide solvent (halogenated alkyl compound).
Examples of the halogenated alkyl solvent include chlorinated solvents, brominated solvents, and fluorinated solvents. A chlorinated solvent means a solvent containing a chlorine atom, a brominated solvent means a solvent containing a bromine atom, and a fluorinated solvent means a solvent containing a fluorine atom. In the following, a chlorinated solvent, a brominated solvent, and a fluorinated solvent will be exemplified. That is, for example, CH ₃ CClF ₂ can be a chlorinated solvent as well as a fluorinated solvent.
The chlorinated solvent may be a halogenated alkyl solvent having only a chlorine atom as a halogen atom.
The bromine-based solvent may be a halogenated alkyl solvent having only a bromine atom as a halogen atom.
The fluorine-based solvent may be a halogenated alkyl solvent having only a fluorine atom as a halogen atom. Examples of the chlorine-based solvent include methylene chloride, chloroform, carbon tetrachloride, ethyl chloride, 1,1-dichloroethane, 1, Examples include 2-dichloroethane, 1-chloropropane, 2-chloropropane, 1-chlorobutane, 2-chlorobutane, 1-chloro-2-methylpropane, and 1-chloropentane.
Examples of brominated solvents include dibromomethane, dibromoethane, tetrabromoethane, isopropyl bromide, normal propyl bromide, bromochloromethane, and 1,2-dibromo-1,1-difluoroethane.
Examples of the fluorine-based solvent include hydrochlorofluoroalkanes such as CH ₃ CClF ₂ , CH ₃ CCl ₂ F, CF ₃ CF ₂ CCl ₂ H, and CF ₂ ClCF ₂ CFHCl;
Chlorofluoroalkanes such as CF ₂ ClCFClCF ₂ CF ₃ , CF ₃ CFClCFClCF ₃ ; and perfluorocyclobutane, CF ₃ CF ₂ CF ₂ CF ₃ , CF ₃ CF ₂ CF ₂ CF ₂ CF ₃ , CF ₃ CF ₂ CF ₂ CF ₂ Perfluoroalkanes such as CF ₂ CF ₃ are mentioned.
The said reaction solvent may be used individually by 1 type, or may be used in combination of 2 or more type. The reaction solvent is more preferably methylene chloride, chloroform, carbon tetrachloride, dibromomethane, or dibromoethane, or a mixed solvent of two or more thereof.
Surprisingly, bromination of 1,1,2-trihaloethane represented by the above formula (1) has a higher priority than bromination of methylene chloride even in the case of using methylene chloride as a solvent in Step A. Progresses to 1,1,2-tribromoethane. Since methylene chloride is available at a low cost, it is advantageous in terms of cost to use methylene chloride as a solvent.
When the raw material compound of Step A is 1,1,2-trichloroethane, from the viewpoint of obtaining 1,1,2-tribromoethane in a particularly high yield, the reaction solvent is preferably a bromine-based solvent, More preferred is a halogenated alkyl solvent having only a bromine atom as a halogen atom, and particularly preferred is dibromomethane.
When step A is carried out in the presence of a reaction solvent, the amount of the reaction solvent is preferably 3 to 30 weights with respect to 1 part by weight of 1,1,2-trihaloethane represented by the formula (1). In the range of parts, more preferably in the range of 3 to 10 parts by weight.
When the raw material compound of step A is 1,2-dibromo-1-chloroethane,
Step A is preferably
In the presence of an alkyl halide as the reaction solvent,
The upper limit of the reaction temperature is preferably 20 ° C, more preferably 10 ° C, still more preferably 0 ° C; and the lower limit of the reaction temperature is preferably -78 ° C, more preferably -60 ° C, More preferably, it is carried out at -40 ° C.
When the raw material compound of step A is 1,1,2-trichloroethane,
Step A is preferably
In the presence of an alkyl halide as a reaction solvent (preferably a bromine-based solvent, more preferably an alkyl halide solvent having only a bromine atom as a halogen atom, particularly preferably dibromomethane),
The upper limit of the reaction temperature is preferably 20 ° C, more preferably 10 ° C, still more preferably 5 ° C; and the lower limit of the reaction temperature is preferably -78 ° C, more preferably -50 ° C, further Preferably, it is carried out under the condition of −30 ° C.

Step A is preferably performed under an inert gas.
Examples of the inert gas include nitrogen.

The method for producing 1,1,2-trihaloethane represented by the formula (1) used in the step A will be described later.

As an example of a specific embodiment of step A, a reaction solvent solution of bromine is dropped into aluminum and a reaction solvent which are put in a reactor, and then 1,1,2-represented by the above formula (1) The method of dripping the reaction solvent solution of trihaloethane is mentioned.

Another example of a specific embodiment of step A includes a method in which bromine is added dropwise to aluminum in a reactor and 1,1,2-trihaloethane represented by the above formula (1).

As yet another example of the specific embodiment of Step A, the reactor is charged with 1,1,2-trihaloethane represented by the above formula (1), the reaction solvent, and bromine, and after mixing these, The method of putting aluminum is mentioned.

As still another example of the specific embodiment of step A, 1,1,2-trihaloethane represented by the above formula (1) is dropped into aluminum bromide in a reactor and a reaction solvent. Is mentioned.

As another example of a specific embodiment of Step A, 1,1,2-trihaloethane represented by the above formula (1) and a reaction solvent are put in a reactor, and after mixing these, aluminum, and Examples include a method of adding bromine in several steps (for example, a method of adding aluminum and dropping bromine three times (three sets), each of which is 1/3 of a predetermined amount).

Method for Producing 1,1-Dibromoethylene The method for producing 1,1-dibromoethylene of the present invention is 1,1,2-tribromo obtained by the method for producing 1,1,2-tribromoethane of the present invention. Ethane is dehydrobrominated using a base to include step B to give 1,1-dibromoethylene.

The 1,1,2-tribromoethane obtained by the method for producing 1,1,2-tribromoethane of the present invention is used as it is, or solvent extraction, drying, filtration, distillation, concentration, or a combination thereof. The product can be purified by the conventional method and used in Step B.

Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, and magnesium hydroxide; inorganic basic salts such as sodium carbonate, potassium carbonate, cesium carbonate, calcium carbonate, and sodium bicarbonate; and amine compounds (E.g., aliphatic primary amines, aliphatic secondary amines, aliphatic tertiary amines, alicyclic secondary amines, alicyclic tertiary amines, aromatic amines, heterocyclic amines, and And organic bases such as polymer-supported amine compounds). Examples of the amine compound include amine compounds exemplified below as stabilizers. The amine compound as a stabilizer described later can also function as the base.
Preferred examples of the base include sodium hydroxide, potassium hydroxide, ammonia, and triethylamine.
The said base may be used individually by 1 type, or may be used in combination of 2 or more type. The combination may be, for example, a combination of an inorganic base and an amine compound exemplified as a stabilizer described later.
The base may be used in the form of an aqueous solution (eg, sodium hydroxide aqueous solution, aqueous ammonia). The water of the aqueous solution can function as a reaction solvent.
The amount of the base is preferably in the range of 0.9 equivalents to 5.0 equivalents, more preferably in the range of 0.9 equivalents to 3.0 equivalents with respect to 1,1,2-tribromoethane. Of these, more preferably in the range of 0.9 equivalents to 2.0 equivalents, still more preferably in the range of 1.0 equivalents to 1.5 equivalents, still more preferably 1.0 equivalents to 1.2 equivalents. Is within the range. As described above, when the amine compound exemplified as the stabilizer functions also as the base, the amount of the base including the amine compound is preferably such an amount.

The upper limit of the reaction temperature in Step B is preferably 100 ° C, more preferably 80 ° C, and still more preferably 60 ° C.
The lower limit of the reaction temperature in Step B is preferably 0 ° C, more preferably 5 ° C, and still more preferably 10 ° C.
The reaction temperature in Step B is preferably in the range of 0 ° C. to 100 ° C., more preferably in the range of 5 ° C. to 80 ° C., still more preferably in the range of 10 ° C. to 60 ° C.

The reaction time of step B is usually in the range of 0.5 to 40 hours.

Step B can be performed preferably in the presence of a stabilizer. In the present specification, the “stabilizer” can be a “polymerization inhibitor”, a “decomposition inhibitor”, or a “polymerization inhibitor” and a “decomposition inhibitor”. The stabilizer can be added to the reaction system before the reaction in Step B and at any time during the reaction. Further, the “before the reaction of Step B” may be any time before the reaction of Step A and during the reaction, which is performed before Step B.
By carrying out Step B in the presence of a stabilizer, the stability of 1,1-dibromoethylene, which is the product of Step B, can be improved.
The stabilizer is preferably, for example, an aliphatic primary amine, an aliphatic secondary amine, an aliphatic tertiary amine, an alicyclic secondary amine, an alicyclic tertiary amine, an aromatic And amine compounds such as aromatic amines, heterocyclic amines, and polymer-supported amine compounds.
Examples of the aliphatic primary amine include methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine, cyclohexylamine, and ethylenediamine.
Examples of the aliphatic secondary amine include dimethylamine, diethylamine, dipropylamine, dibutylamine, dipentylamine, dihexylamine, and dicyclohexylamine.
Examples of the aliphatic tertiary amine include trimethylamine, triethylamine, diisopropylethylamine, tributylamine, and N, N, N ′, N′-tetramethylethylenediamine.
Examples of the alicyclic secondary amine include piperidine, piperazine, pyrrolidine, and morpholine.
Examples of the alicyclic tertiary amine include N-methylpiperazine, N-methylpyrrolidine, 5-diazabicyclo [4.3.0] nonane-5-ene, and 1,4-diazabicyclo [2.2.2]. ] Octane is mentioned.
Examples of the aromatic amine include aniline, methylaniline, dimethylaniline, N, N-dimethylaniline, haloaniline, and nitroaniline.
Heterocyclic amines include, for example, pyridine, melamine, pyrimidine, piperazine, quinoline, and imidazole.
Examples of the polymer-supported amine compound include polyallylamine and polyvinyl pyridine.
Moreover, as a stabilizer other than the above (that is, a stabilizer other than an amine compound),
(1) a compound having a hydroxyl group,
(2) a compound having a sulfide bond,
(3) A group comprising a compound having a thiophenolic or thiol sulfur atom, and (4) a sulfite compound (5) a nitrous acid compound (in this specification, this group may be referred to as a compound group (C). 1 or more compounds selected from (in the present specification, the compound may be referred to as a compound (C)).
The said compound (C) may be used individually by 1 type, or may be used in combination of 2 or more type.
Examples of the “(1) hydroxyl group-containing compound” include, for example, a formula such as methanol, ethanol, isopropyl alcohol, and t-butanol: R—OH (wherein R is, for example, an alkyl having 1 to 6 carbon atoms) An alcohol represented by a group; and phenolhydroquinone, 4-methoxyphenol, 2,5-di-tert-butylhydroquinone, methylhydroquinone, tert-butylhydroquinone (TBH), p-benzoquinone, methyl-p -Substituted with one or more hydroxyl groups such as benzoquinone, tert-butyl-p-benzoquinone, 2,5-diphenyl-p-benzoquinone, and 2,6-di-tert-butyl-4-methylphenol (BHT) A compound having a partial structure which is a benzene ring (wherein the hydroxyl group is Kiso may be made based on (O =). The number of carbon atoms in the compound is preferably a 6-20.) (Hereinafter, the compound may be simply referred to as phenolic compounds.) Can be mentioned.
Examples of the “(2) compound having a sulfide bond” include, for example, a dialkyl sulfide (the two “alkyl” have the same or different carbon number, preferably 1 to 6), and a diphenyl sulfide structure. (Eg, compounds having a phenyl sulfide structure and having a sulfide bond having 6 to 20 carbon atoms, such as diphenyl sulfide and phenothiazine).
Examples of the “(3) compound having a thiophenolic or thiol sulfur atom” include R (—SH) such as thiophenol, benzenedithiol, 1,2-ethanedithiol, and 1,3-propanedithiol. _n [wherein R represents, for example, an alkane having 1 to 6 carbon atoms or an aromatic carbocyclic ring having 6 to 12 carbon atoms (eg, benzene, diphenyl); and n represents, for example, 1 or 2 Represents an integer. ] The compound represented by this is mentioned.
Examples of the “(4) sulfite compound” include potassium sulfite, calcium sulfite, sodium hydrogen sulfite, sodium sulfite, barium sulfite, magnesium sulfite, dimethyl sulfite, diethyl sulfite, diamyl sulfite, dipropyl sulfite, and diisopropyl sulfite. .
Examples of the “(5) nitrite compound” include potassium nitrite, sodium nitrite,
Mention may be made of methyl nitrite, ethyl nitrite, amyl nitrite, propyl nitrite and isopropyl nitrite.

The compound (C) as a stabilizer described above is
Is preferably “(1) a compound having a hydroxyl group”, more preferably a phenol compound.
Preferred examples of the stabilizer include diisopropylethylamine, tributylamine, triethylamine, 4-methoxyphenol, 2,6-di-tert-butyl-4-methylphenol (BHT), pyridine, melamine, and phenothiazine. It is done.
The said stabilizer may be used individually by 1 type, or may be used in combination of 2 or more type.
In a preferred embodiment of the present invention, Step B is carried out in the presence of (1) one or more amine compounds and (2) one or more compounds (C), each of which can function as a stabilizer. The
When a stabilizer is used in Step B, the total amount thereof is preferably in the range of 100 to 50,000 ppm (w / w), more preferably 100 to 10000 ppm (with respect to 1,1,2-tribromoethane). w / w), more preferably 100 to 3000 ppm (w / w), even more preferably 100 to 3000 ppm (w / w), particularly preferably 500 to 2000 ppm (w / w). And more particularly preferably in the range of 500 to 1500 ppm (w / w).

As described above, the amine compound as the stabilizer can also function as the base. However, when Step B is carried out in the presence of the stabilizer, preferably an inorganic base as the base and a stable It is preferable to use in combination with an amine compound as an agent. However, it is within the scope of the present invention that the amine compound as a stabilizer functions as a base, while it is also within the scope of the present invention that the amine compound as a base functions as a stabilizer. .

In a particularly preferred embodiment of the present invention, after purification of 1,1,2-tribromoethane produced in Step A, one or more amine compounds are added thereto, and the resulting composition is treated with Step B. Used for.

The reaction of step B is preferably carried out in the presence of a reaction solvent.
Examples of the reaction solvent include a water-soluble solvent, water, and a mixed solvent of two or more thereof.
The reaction solvent is preferably a water-soluble solvent or a mixed solvent of a water-soluble solvent and water. The mixed solvent of water-soluble solvent and water is a mixed solvent containing a water-soluble solvent and water, and may contain a solvent other than these, but preferably consists essentially of a water-soluble solvent and water, More preferably, it consists only of a water-soluble solvent and water. In the mixed solvent, water may be derived from an aqueous base solution as described above.
As the reaction solvent or the water-soluble solvent in the reaction solvent, for example,
Alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and t-butyl alcohol;
Ketones such as acetone and methyl ethyl ketone (MEK);
And ethers such as diethyl ether and tetrahydrofuran (THF); and acetic acid, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), dimethylacetamide (DMAc), 1-methyl-2-pyrrolidone (NMP), etc. Preferably, the organic solvent is methanol, DMF, THF, or NMP.
By using such a solvent, the purification of 1,1-dibromoethylene obtained in Step B can be easily carried out without distillation by washing with water or the like. The risk of polymerization of can be reduced.
The amount of the reaction solvent is usually within a range of 0 to 20 parts by weight, preferably within a range of 0.1 to 15 parts by weight, more preferably, with respect to 1 part by weight of 1,1,2-tribromoethane. Within the range of 0.1 to 10 parts by weight.
When Step B is performed in the presence of water and in the absence of a water-soluble organic solvent, it is preferable to use a phase transfer catalyst. The water can be water as the “reaction solvent” or water of an aqueous solution of the base.
Examples of the phase transfer catalyst include quaternary ammonium such as tetramethylammonium chloride, tetraethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium sulfate, and trioctylmethylammonium chloride. Salts; quaternary phosphonium salts such as tetrabutylphosphonium chloride; pyridinium compounds such as dodecylpyridinium chloride; and crown ethers.
Of these, tetramethylammonium chloride or tetrabutylammonium bromide is preferable.
When a phase transfer catalyst is used, the amount thereof is preferably within a range of 0.01 equivalents to 1 equivalent, more preferably 0.01 equivalents to 0.5 equivalents relative to 1,1,2-tribromoethane. Within the range of equivalents, more preferably within the range of 0.01 equivalents to 0.1 equivalents.

As an example of a specific embodiment of Step B, a reaction of a base with 1,1,2-tribromoethane, a reaction solvent, and a stabilizer, which are produced in the production method of the present invention, is put in a reactor. The method of adding a solvent solution is mentioned.

The 1,1-dibromoethylene obtained by the production method can be isolated or purified by a conventional method such as adding water for liquid separation, if necessary.

After the reaction in Step B, a stabilizer may be added to the product. “After the reaction of Step B” can be after isolation or purification of 1,1-dibromoethylene. Thus, the storage stability of the product can be improved by adding a stabilizer to the product after the reaction in Step B. Examples of the stabilizer include the same stabilizers used before and after the reaction in Step B and at any time during the reaction (that is, during the reaction in Step B).
When a stabilizer is used both during the reaction of Step B and after the reaction of Step B, the stabilizer added to the product after the reaction of Step B is the same as the stabilizer used during the reaction of Step B. May be different.
From the viewpoint of reactivity and stability, the stabilizer used after the reaction in the step B is preferably different from the stabilizer used in the reaction in the step B.
Similarly, from the viewpoint of reactivity and stability, at least one of the two or more stabilizers used after the reaction in Step B is different from the stabilizer used in the reaction in Step B. It is also preferable.
More preferably, one or more amine compounds that can function as a stabilizer are added before the reaction in Step B, and the one or more compounds (C) that can function as a stabilizer after the reaction in Step B. Add. The compound (C) is preferably the “(1) hydroxyl group-containing compound”, and more preferably a phenol compound.
Specifically, in a preferred embodiment of the present invention, for example, triethylamine is added to the reaction system before or during the reaction of Step B, and BHT is added after the reaction of Step B (preferably 1 , After the isolation or purification of 1-dibromoethylene).
The amount of stabilizer added to the product after the reaction of Step B is preferably in the range of 100 to 3000 ppm (w / w), more preferably 100 to 2000 ppm relative to 1,1-dibromoethylene. Within the range of (w / w), more preferably within the range of 100 to 1500 ppm (w / w).

In one embodiment of the present invention, Step B includes (1) one or more amine compounds that can function as a stabilizer, and (2) the compound (C) that can function as a stabilizer (preferably, It is carried out in the presence of “(1) a compound having a hydroxyl group”, more preferably a phenol compound).
Particularly preferably, Step B is carried out in the presence of one or more amine compounds and 2,6-di-tert-butyl-4-methylphenol (BHT).
In the reaction of Step B, (1) one or more amine compounds, and (2) the one or more compounds (C) (preferably, “(1) a compound having a hydroxyl group”, more preferably a phenol compound. Particularly preferably, BHT) can be added to the reaction system before the reaction in Step B and at any time during the reaction (that is, during the reaction in Step B), but it must be added before the reaction in Step B. Is preferred. The reaction is new.

Thus, the amount of the one or more amine compounds added to the reaction system of Step B is preferably within a range of 100 to 50000 ppm (w / w), more preferably with respect to 1,1-dibromoethylene. In the range of 100 to 10,000 ppm (w / w), more preferably in the range of 100 to 3000 ppm (w / w), still more preferably in the range of 100 to 2000 ppm (w / w), particularly preferably It is within the range of 100-1500 ppm (w / w).
As described above, one or more compounds (C) (preferably “(1) a compound having a hydroxyl group”, more preferably a phenol compound, and particularly preferably BHT) added to the reaction system of Step B) Is preferably in the range of 100 to 50000 ppm (w / w), more preferably in the range of 100 to 10000 ppm (w / w), still more preferably 100 It is within the range of -3000 ppm (w / w), more preferably within the range of 100-2000 ppm (w / w), and particularly preferably within the range of 100-1500 ppm (w / w).

As an alternative to 1,1-dibromoethylene, the same method as the above-described method for producing 1,1-dibromoethylene of the present invention, except that 1,1,2-tribromoethane is used instead.
(1) 1,1,1-tribromoethane or (2) 1,1,2-tribromoethane and 1,1,1-tribromoethane can also be used for production.

Specifically, 1,1-dibromoethylene can be produced, for example, by the production method described below.
The 1,1-dibromoethylene is produced by dehydrobromination of 1,1,2-tribromoethane and / or 1,1,1-tribromoethane using a base to obtain 1,1- Obtaining dibromoethylene.
At any point in time for the step, that is, before the reaction in the step, during the reaction, and at any point after the reaction, (1) one or more amine compounds and ( 2) The 1,1-dibromoethylene composition of the present invention can be produced by adding one or more compounds (C).
For example, (1) one or more amine compounds and (2) one or more compounds (C) may be added as follows:
An aspect of adding both from the beginning of the step (this includes “before the reaction of the step”),
A mode in which one is added from the beginning of the step and the other is added after the start of the reaction in the step (this includes “after the reaction in the step”),
A mode in which one is added from the beginning of the step and both are added after the start of the reaction in the step (that is, a mode in which the “one” is further added),
A mode in which both are added after completion of the reaction without adding them at the beginning of the process,
An embodiment in which both are added simultaneously during the reaction without adding them at the beginning of the step and an embodiment in which both are added separately during the reaction without adding them at the beginning of the step are exemplified. The

1,1,1-tribromoethane can be produced by a known method or a method analogous thereto.

Method for producing 1,2-dibromo-1-chloroethane As mentioned above, 1,2-dibromo-1-chloroethane used in Step A is, for example,
It can be suitably produced by a method including the step C of adding bromine to vinyl chloride.

The addition of bromine to vinyl chloride can be carried out, for example, by reacting vinyl chloride with bromine.
The amount of bromine is preferably in the range of 0.9 equivalents to 2.0 equivalents, more preferably in the range of 1.0 equivalents to 1.5 equivalents, and even more preferably 1.0 equivalents relative to vinyl chloride. Within the range of ˜1.1 equivalents.

The upper limit of the reaction temperature in Step C is preferably 55 ° C, more preferably 40 ° C, and further preferably 30 ° C.
The lower limit of the reaction temperature in Step C is preferably −5 ° C., more preferably 0 ° C., and still more preferably 5 ° C.
The reaction temperature in Step C is preferably in the range of −5 ° C. to 55 ° C., more preferably in the range of 0 ° C. to 40 ° C., and still more preferably in the range of 5 ° C. to 30 ° C.

The reaction time of step C is usually within a range of 1 to 20 hours.

Step C can be carried out in the presence or absence of a reaction solvent.
The said solvent is carbon tetrachloride, chloroform, and those mixed solvents, for example.

As an example of a specific embodiment of Step C, there is a method of introducing or press-fitting vinyl chloride into a reactor containing bromine by bubbling.

When vinyl chloride is injected, the pressure in the reactor (internal pressure) (gauge pressure) is preferably in the range of 0.01 MPa to 0.3 MPa, more preferably in the range of 0.05 MPa to 0.25 MPa. More preferably, it is in the range of 0.05 MPa to 0.2 MPa.

The 1,2-dibromo-1-chloroethane obtained by the production method can be used in Step A as it is or after being purified by a conventional method such as distillation under reduced pressure or concentration.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

In the following examples, gas chromatography (GC) was performed according to the following GC conditions.
<GC conditions>
GC equipment; SHIMADZU GC-2010
Column: J & W DB-5MS (0.25 μm, 60 m, 0.25 mm ID)
Column oven: 40 ° C. (4 minutes) → Temperature rise (10 ° C./min)→300° C. (0 minute)
Vaporization chamber temperature: 200 ° C

Example C1
Bromine (50 g, 315 mmol) was added to a reactor equipped with a stirrer, and vinyl chloride (21.5 g, 344 mmol) was injected under cooling. Thereafter, the temperature was raised to room temperature, and the mixture was stirred overnight for 17 hours to complete the reaction. The obtained crude product was purified by distillation under reduced pressure to obtain 1,2-dibromo-1-chloroethane (67.6 g, yield 97%) as a colorless oil.

Example C2
Bromine (500 g, 3.13 mol) was added to the reactor, and while cooling, vinyl chloride was added until the bromine color disappeared, and 1,2-dibromo-1-chloroethane (696.5 g, 100% yield) was colorless. Obtained as an oil.

Example A1
After the atmosphere in the reactor was replaced with nitrogen, aluminum (109 mg, 4.05 mmol) and dichloromethane (30 mL) were added. The mixture was cooled to −20 ° C. with stirring, and a solution of bromine (1.07 g, 6.75 mmol) in dichloromethane (20 mL) was added dropwise. After stirring at −20 ° C. for 15 minutes, a solution of 1,2-dibromo-1-chloroethane (3 g, 13.5 mmol) in dichloromethane (20 mL) was added dropwise. After stirring at −20 ° C. for 1 hour, the mixture was poured into ice water. After stirring for a while, liquid separation was performed to obtain 1,1,2-tribromoethane (GC area 74%), and 1,2-dibromo-1-chloroethane (GC area 20%) as a raw material was recovered.

Example A2
1,1,2-tribromoethane (GC area 89%) was obtained in the same manner as in Example A1, except that the equivalent of aluminum to 1,2-dibromo-1-chloroethane was changed to 0.4 and the equivalent of bromine to 0.65. As a result, 1,2-dibromo-1-chloroethane (GC area 9%) as a raw material was recovered.

Example A3
Example A1 except that the weight ratio of 1,2-dibromo-1-chloroethane to dichloromethane was changed to 1:10 (where the amount of 1,2-dibromo-1-chloroethane is the same as in Example A1). Similarly, 1,1,2-tribromoethane (GC area 73%) was obtained, and 1,2-dibromo-1-chloroethane (GC area 26%) as a raw material was recovered.

Example A4
The equivalent of aluminum to 1,2-dibromo-1-chloroethane was changed to 0.5, the equivalent of bromine to 0.8, and the weight ratio of 1,2-dibromo-1-chloroethane to dichloromethane was changed to 1:10 (where The amount of 1,2-dibromo-1-chloroethane is the same as in Example A1, except that 1,1,2-tribromoethane (GC area 97%) is obtained in the same manner as in Example A1. Some 1,2-dibromo-1-chloroethane (GC area 2%) was recovered.

Example A5
The equivalent of aluminum to 1,2-dibromo-1-chloroethane was changed to 0.5, the equivalent of bromine to 0.5, and the weight ratio of 1,2-dibromo-1-chloroethane to dichloromethane was changed to 1:10 (where The amount of 1,2-dibromo-1-chloroethane is the same as in Example A1, except that 1,1,2-tribromoethane (GC area 89%) is obtained in the same manner as in Example A1. Some 1,2-dibromo-1-chloroethane (GC area 5%) was recovered.

Example A6
A brominated product of 1,1,2-tribromoethane (GC area 20%), dichlorobromoethane (GC area 14%), and dichloromethane, except that the reaction temperature was changed to 0 ° C. (GC area 37%) was obtained, and 1,2-dibromo-1-chloroethane (GC area 29%) as a raw material was recovered.

Example A7
After the atmosphere in the reactor was replaced with nitrogen, aluminum (60.7 mg, 2.25 mmol) and 1,2-dibromo-1-chloroethane (1 g, 4.5 mmol) were added. The mixture was cooled to −20 ° C. with stirring, and bromine (360 mg, 2.25 mmol) was added dropwise. After stirring at −20 ° C. for 1 hour, the mixture was poured into ice water. After stirring for a while, liquid separation was performed to obtain 1,1,2-tribromoethane (GC area 48%), and 1,2-dibromo-1-chloroethane (GC area 52%) as a raw material was recovered.

Example A8
Except that the reaction time was changed to 5.5 hours, 1,1,2-tribromoethane (GC area 90%) was obtained in the same manner as in Example A7, and the raw material 1,2-dibromo-1-chloroethane ( GC area 0.3%) was recovered.

Example A9
After the atmosphere in the reactor was replaced with nitrogen, aluminum (60 mg, 2.25 mmol) and 1,2-dichloroethane (8 mL) were added. The mixture was cooled to −20 ° C. with stirring, and bromine (360 mg, 2.25 mmol) was added dropwise. After stirring at −20 ° C. for 15 minutes, 1,2-dibromo-1-chloroethane (1 g, 4.5 mmol) was added dropwise. After stirring at −20 ° C. for 1 hour, the mixture was poured into ice water. After stirring for a while, liquid separation was performed to obtain 1,1,2-tribromoethane (GC area 32%) and a brominated product of 1,2-dichloroethane (GC area 30%), and the raw material 1, 2-Dibromo-1-chloroethane (GC area 34%) was recovered.

Example A10
After the atmosphere in the reactor was replaced with nitrogen, aluminum bromide (396 mg, 1.49 mmol) and dichloromethane (7.6 mL) were added. The mixture was cooled to −20 ° C. with stirring, and 1,2-dibromo-1-chloroethane (1 g, 4.5 mmol) was added dropwise. After stirring at −20 ° C. for 1 hour, the mixture was poured into ice water. After stirring for a while, liquid separation was performed to obtain 1,1,2-tribromoethane (GC area 92%).

Example A11
After the atmosphere in the reactor was replaced with nitrogen, aluminum (60.7 mg, 2.25 mmol) and dibromomethane (30 g) were added. The mixture was cooled to 0 ° C. with stirring, and bromine (360 mg, 2.25 mmol) was added dropwise. After stirring at 0 ° C. for 15 minutes, 1,2-dibromo-1-chloroethane (1 g, 4.5 mmol) was added dropwise. After stirring at 0 ° C for 1 hour, the mixture was poured into ice water. After stirring for a while, liquid separation was performed to obtain 1,1,2-tribromoethane (GC area 82%), and 1,2-dibromo-1-chloroethane (GC area 2%) as a raw material was recovered.

Example A12
After the atmosphere in the reactor was replaced with nitrogen, aluminum (240 mg, 8.90 mmol) and dibromomethane (30 g) were added. The mixture was cooled to −20 ° C. with stirring, and bromine (1.8 g, 11.3 mmol) was added dropwise. After stirring at −20 ° C. for 15 minutes, 1,1,2-trichloroethane (1 g, 7.50 mmol) was added dropwise. The temperature was raised to 0 ° C., stirred for 5.5 hours, and then poured into ice water. After stirring for a while, liquid separation was performed to obtain 1,1,2-tribromoethane (GC area 88%), chlorodibromoethane (GC area 2%), and various kinds of unknown structures. 1,2-trichloroethane (GC area 5%) was recovered.

Example A13
After purging the inside of the reactor with nitrogen, 1,2-dibromo-1-chloroethane (50 g, 225 mmol), dichloromethane (250 g), and bromine (19.8 g, 125 mmol) were added. Cool to −10 ° C. with stirring and add aluminum (2.43 g, 90 mmol). After stirring at the same temperature for 1 hour, it was poured into ice water. After stirring for a while, liquid separation was performed to obtain 1,1,2-tribromoethane (GC area 84%), and 1,2-dibromo-1-chloroethane (GC area 15%) as a raw material was recovered.

Example A14
After the atmosphere in the reactor was replaced with nitrogen, 1,2-dibromo-1-chloroethane (1000 g, 3.75 mol) and dichloromethane (4000 mL) were added. The mixture was cooled to −20 ° C. with stirring, aluminum (20.3 g, 752 mmol) was added, and bromine (192 g, 1.20 mol) was added dropwise. This addition operation was performed three times in total. After stirring at the same temperature for 3 hours, the mixture was poured into ice water. After stirring for a while, liquid separation was performed to obtain a crude product. The obtained crude product was purified by distillation to obtain 1,1,2-tribromoethane (yield 94%, GC area 99%).

Example B1
Methanol (0.3 g), 1,1,2-tribromoethane (3.0 g, 11.2 mmol) and Et ₃ N (5 mg) were added to the reactor. Further, 25% aqueous sodium hydroxide solution (1.97 g, 12.3 mmol) was added, and the mixture was heated to 50 ° C. with stirring. After stirring at the same temperature for 20 hours, liquid separation was performed to obtain 1,1-dibromoethylene (1.68 g, yield 81%, GC area 98.7%) as a colorless oil.

Example B2
To the reactor, DMF (1 g), 1,1,2-tribromoethane (1.0 g, 3.75 mmol), Et ₃ N (1 mg) were added. After adding sodium hydroxide (165.2 mg, 4.13 mmol), the mixture was heated to 50 ° C. with stirring. After completion of the reaction, water was added for liquid separation to obtain 1,1-dibromoethylene (GC area 96.5%) as a colorless oil.

Example B3
To the reactor was added THF (1 g), 1,1,2-tribromoethane (1.0 g, 3.75 mmol), Et ₃ N (1 mg). After adding sodium hydroxide (165.2 mg, 4.13 mmol), the mixture was heated to 50 ° C. with stirring. After completion of the reaction, water was added and the mixture was separated to give 1,1-dibromoethylene (GC area 95.4%) as a colorless oil.

Example B4
To the reactor, NMP (1 g), 1,1,2-tribromoethane (1.0 g, 3.75 mmol) and Et ₃ N (1 mg) were added. After adding sodium hydroxide (165.2 mg, 4.13 mmol), the mixture was heated to 50 ° C. with stirring. After completion of the reaction, water was added and the mixture was separated to give 1,1-dibromoethylene (GC area 92.4%) as a colorless oil.

Example B5
Methanol (0.5 g), 1,1,2-tribromoethane (5.0 g, 18.7 mmol) and Et ₃ N (189 mg, 1.87 mmol) were added to the reactor. A 50% aqueous sodium hydroxide solution (1.65 g, 20.6 mmol) was added to the mixed solution, and the mixture was stirred at room temperature for 15 hours. Analysis by NMR and GC gave 1,1-dibromoethylene (94% yield).

Example B6
Methanol (0.5 g), 1,1,2-tribromoethane (5.0 g, 18.7 mmol) and Et ₃ N (5 mg) were added to the reactor. A 50% aqueous sodium hydroxide solution (1.65 g, 20.6 mmol) was added to the mixed solution, and the mixture was stirred at room temperature for 15 hours. Analysis by NMR and GC gave 1,1-dibromoethylene (yield 91%, GC area 98.8%).

Example B7
Tetramethylammonium chloride (205.5 mg, 1.875 mmol), 1,1,2-tribromoethane (10 g, 37.5 mmol) and Et ₃ N (10 mg) were added to the reactor. Under ice-cooling, 50% aqueous sodium hydroxide solution (3.3 g, 41.3 mmol) was added, and the mixture was stirred at room temperature for 51 hours and then separated to give 1,1-dibromoethylene (GC area 56%) as a colorless oil. Got as.

1,1,2-tribromoethane and 1,1-dibromoethylene obtained by the production method of the present invention are pharmaceutical intermediates (for example, antibiotics), synthetic intermediates for optical fiber sheath materials, It is a compound useful as a synthetic intermediate for coating materials, a synthetic intermediate for semiconductor resist materials, a synthetic intermediate for monomers of functional polymers, and the like.

Claims

A method for producing 1,1,2-tribromoethane having the formula (1):

[Where:
X ¹ , X ² , and X ³ represent a chlorine atom or a bromine atom.
However, at least one of X ¹ , X ² , and X ³ is a chlorine atom. ]
Represented by
A production method comprising a step A in which 1,1,2-trihaloethane is brominated to obtain 1,1,2-tribromoethane.

The production method according to claim 1, wherein the 1,1,2-trihaloethane represented by the formula (1) is 1,2-dibromo-1-chloroethane or 1,1,2-trichloroethane.

The process according to claim 1 or 2, wherein in step A, 1,1,2-trihaloethane represented by the formula (1) is reacted with aluminum and bromine to obtain 1,1,2-tribromoethane.

In step A, 1,1,2-trihaloethane represented by the formula (1) is reacted with an aluminum halide having one or more bromine atoms to obtain 1,1,2-tribromoethane. 4. The production method according to any one of items 1 to 3.

The method according to claim 4, wherein the aluminum halide having one or more bromine atoms is aluminum bromide.

The process according to any one of claims 1 to 5, wherein the reaction temperature in step A is in the range of -78 ° C to 20 ° C.

The production method according to any one of claims 1 to 6, wherein Step A is carried out in the presence of an alkyl halide compound as a reaction solvent.

A method for producing 1,1-dibromoethylene, wherein 1,1,2-tribromoethane obtained by the production method according to any one of claims 1 to 7 is dehydrobrominated using a base. And the production method comprising the step B of obtaining 1,1-dibromoethylene.

The production method according to claim 8, wherein Step B is carried out in the presence of a water-soluble organic solvent as a reaction solvent or a mixed solvent of a water-soluble organic solvent and water.

The production method according to claim 8, wherein Step B is carried out using a phase transfer catalyst in the presence of water and in the absence of a water-soluble organic solvent.