JPH0446937B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for the preparation of halohydrins, which are 1,1-bis[(optionally substituted) phenyl]-2-haloalkan-1-ols.

German Patent No. 1172654 describes and claims a process for preparing chlorohydrin by reacting olefins or polyolefins with chlorine in an aqueous medium, which may be substituted or branched. or an olefin or polyolefin having from 5 to 40 carbon atoms in the molecule, which may be cyclic, can be mixed with the water and the olefin or polyolefin used.
The method includes reacting with chlorine in a liquid reactive medium containing at least 50 parts by volume (based on 100 parts by volume of water) of an organic solvent having a boiling point below .degree.

In particular, the organic solvent used in the above method should be heated at 150°C.
, especially below 100° C., and which contain only carbon, hydrogen and oxygen in the molecule, such as alcohols, ethers, aldehydes, ketones, carboxylic acids and carboxylic acid esters. The olefin used as a starting material is typically a mixture of hexadecene-1 and _C13 - _C15 -alkenes.

According to the invention, the formula: [wherein R and R ¹ are hydrogen, X is chlorine or fluorine, and Y and Z are each independently hydrogen, fluorine or chlorine, provided that Y and Z are not both hydrogen or both halogen and A is chlorine or bromine], which has the formula: The substituted alkene of formula [wherein R, R ¹ , X, Y and Z are as defined above] is treated with chlorine, bromine, This includes reacting with hypochlorous acid or hypobromous acid.

The proportion of water to amide solvent is advantageously such that the amount of water is the maximum that can be used without forming two layers in the reaction mixture. Generally, this amount is approximately 25% w/water and solvent together.
It is w. The halohydrin yield can be adversely affected if two layers are formed.

A particularly advantageous method is to carry out the reaction in the presence of hydrogen peroxide. In this case, the overall reaction can be expressed by: From the above formula it is clear that 2 moles of alkene () requires 1 mole of chlorine or bromine and 1 mole of hydrogen peroxide to form 2 moles of halohydrin (). Although this optimal theoretical stoichiometry may not be achieved in practice, particularly good methods ensure that most of the halogen used is used for halohydrin formation.

The amount of chlorine or bromine used is the alkene 2 of the formula
An excess of slightly more than 1 mol per mol, preferably from 1.1 to 1.5 mol per 2 mol of alkene.

The same considerations apply when using hydrogen peroxide regarding its amount. In general, a greater amount of chlorine or bromine and hydrogen peroxide than that indicated by the above reaction equation is likely to be present in the reactants, possibly due to the known reactions that take place between these reactants, resulting in the loss of some of the reactants chlorine or bromine and hydrogen peroxide from the system. Chlorine or bromine and hydrogen peroxide must be used. Hydrogen peroxide is commercially available at 30% (100%
volume) - advantageously used in the form of an aqueous solution, but
Other concentrations can be used if desired.

When hypochlorous acid or hypobromous acid is used in the process, they may be added in the form of dilute aqueous solutions or an alkali metal salt of hypochlorous acid or hypobromous acid, such as a sodium or potassium salt. Alternatively, it may be formed in situ by adding an aqueous solution of a salt such as an alkaline earth metal salt, such as a calcium salt. Particularly good salts of hypochlorous acid are sodium hypochlorite, since they are commercially available in the form of aqueous solutions; optionally mixtures of halide and oxyhalide salts, e.g. bromide and bromate; Mixtures can be used.

Since an amide solvent is used, the temperature range from normal room temperature to approx.
Reaction temperatures up to 100°C are common. The reaction can be carried out by adding an alkene of the formula to a mixture of water and an amide solvent, followed by addition of chlorine or bromine and especially hydrogen peroxide to the mixture, while maintaining the desired reaction temperature. A useful working concentration of the alkene in the aqueous solvent mixture is about 15% w/w, but concentrations up to about 30% w/w or even higher can be applied.

In particular, the reaction can be carried out by adding the alkene to the aqueous amide solvent followed by the addition of chlorine or bromine and, if used subsequently, hydrogen peroxide. Optionally, chlorine or bromine and hydrogen peroxide are added simultaneously or optionally in small amounts to the alkene, amide solvent and water;
Chlorine or bromine and hydrogen peroxide may be added simultaneously or in portions to the amide solvent and water mixture.
If the reaction mixture is tested after all the halogens have been added and it is observed that some alkenes remain unreacted, chlorine or bromine and hydrogen peroxide can be added until all the alkenes have been used. can. The product can be separated during the reaction, or if the proportions of amide solvent and water do not allow this, it can be isolated from the reaction mixture by diluting it with water, generally An oil forms, which can crystallize after stirring at room temperature for a certain period of time. The crude product is collected, washed with water and dried. The process may be operated batchwise or continuously.

Substituted alkenes of the formula that can be used as starting materials in the present invention are, for example, of the formula: It is obtained by heating an alcohol of the formula in which R, R ¹ , X, Y and Z are as defined above in the presence of a catalytic amount of a strong acid such as p-toluenesulfonic acid.

The substituted alke of the formula is also directly described above: RR ¹ HCMgHal () [wherein R and R ¹ represent the above, and Hal
represents chlorine, bromine or iodine] and the alkylmagnesium halide of the formula: The intermediate alcohol of the formula can be produced without isolation from the Grignard reaction of [wherein X, Y and Z are as defined above] with benzophenone. After the reaction is complete, pour the Grignard reaction mixture into dilute aqueous acid and collect the organic layer. This organic layer contains the alcohol of formula in the organic solvent or mixture of organic solvents used in carrying out the formation of the Grignard compound and its subsequent reaction with benzophenone, such as a mixture of tetrahydrofuran and toluene. A dehydrating agent is added to the organic layer and the whole is heated to facilitate dehydration of the intermediate alcohol.

A benzophenone of the formula can be prepared in a known manner by the formula: [In the formula, Y and Z represent the above, and
Hal′ represents bromine or preferably chlorine] and a benzoyl halide of the formula: It can be produced by a Friedel-Crafts reaction of the benzene derivative [wherein X represents the above] in the presence of a Lewis acid such as aluminum chloride.

Optionally, the alcohol of formula: [In the formula, R, R ¹ , Y and Z represent the above]
The formula for the compound is: It can be obtained by reacting with a Grignard compound of the formula [wherein X represents the above-mentioned compound and Hal'' is bromine or iodine].

Compounds of formula XI can be prepared by methods known in the art, for example, acid halides of formula: RR ¹ CH.COA () [A, R and R ¹ are as defined above]: It can be obtained by a Friedel-Crafts reaction with a benzene derivative of [wherein Y and Z are as defined above].

The halohydrin of the formula is of the formula: An intermediate for producing a fungicidal compound of the formula in which X, Y and Z are as defined above.

Compounds of the formula and their preparation, including from halohydrins of the formula, are described in European Patent Application No. 0015756. Generally they are the formula: epoxides, which are usually formed from halohydrins under conditions of basic triazole addition.

Halohydrins of the formula that are particularly useful for synthesizing fungicidal compounds of the formula are those in which X , Y , and Z have the following substitution pattern: These halohydrins are another object of the invention.

Next, the present invention will be explained in detail with reference to examples. In this case, "parts" and "%" are "parts by weight" and "% by weight."

Example 1 A solution of 1,1-bis(4-fluorophenyl)ethene (23.5 parts), dimethylformamide (161 parts) and water (46 parts) was stirred at 44°C and bromine (25
part) over a period of about 3 hours. Water (1500
The product is obtained as an oil which crystallizes out on stirring at room temperature. Filtration, washing with water and drying in vacuo at 60°C gave the crude product (33.6 parts), which was 1,1-
Contains 96% (by quantitative PMR) of bis(4-fluorophenyl)-2-bromoethanol (95% conversion based on 1,1-bis(4-fluorophenyl)ethene). Pure samples were obtained by recrystallization from petroleum ether (100-120°), with melting point
It has a temperature of 72.5-73.5℃.

Example 2 A solution of 1,1-bis(4-fluorophenyl)ethene (46.7 parts), dimethylformamide (388 parts) and water (113 parts) was stirred at 45°C and chlorine (18.4 parts) was added for 5 hours. Add across. solution
Cool to 20°C and add water (1000 parts). An oil forms which crystallizes out on stirring. The chlorohydrin is isolated by filtration and washed with water.
After drying in a vacuum oven at 60° C., crude chlorohydrin (60.3 parts) is obtained. This is 1,1-bis(4
-chlorophenyl)-2-chloroethanol 76.5
% (by PMR and GLC), which is 1,
The conversion rate from 1-bis(4-fluorophenyl)ethene is 80%. A pure sample was obtained by recrystallization from hexane and has a melting point of 83-84°C.

The 1,1-bis(4-fluorophenyl)ethene used in this example can be produced as described in Journal of the Chemical Society, pp. 567-570 (1942). can.

Example 3 A solution of 1-(2-chlorophenyl)-1-(4-fluorophenyl)ethene (22 parts), dimethylformamide (161 parts) and water (50 parts) was stirred at 60°C, and bromine (18.7 parts) was stirred at 60°C. ) over 45 minutes. After pouring the reaction mixture into water (500 parts), the product is extracted with chloroform (200 parts). After washing the extract with 10% hydrochloric acid (900 parts) and then with water (500 parts), the chloroform was removed under vacuum, leaving the crude product (32.0 parts), which was 1-(2-
Chlorphenyl)-1-(4-fluorophenyl)
Contains 72.7% (by quantitative PMR) of -2-bromethanol (conversion rate 74.6% based on 1-(2-chlorophenyl)-1-(4-fluorophenyl)ethene).

Example 4 A solution of 1-(2-fluorophenyl)-1-(4-fluorophenyl)ethene (95 parts), dimethylformamide (64.6 parts) and water (200 parts) was heated at 60°C.
Stir at and add bromine (80 parts) over a period of 3 hours. After pouring the reaction mixture into water (2000 parts) and extracting with chloroform (500 parts), the extract was
Wash with 10%-hydrochloric acid (2000 parts) and then water (1000 parts).
The chloroform was then removed under vacuum leaving the crude product (126.3 parts), which was 1-(2-fluorophenyl)-1-(4-fluorophenyl)-
It contains 87.1% of 2-bromoethanol (according to quantitative PMR), which corresponds to a conversion of 1-(2-fluorophenyl)-1-(4-fluorophenyl)ethene of 87.5%.

Example 5 Dimethylformamide (280 parts) and water (80 parts)
A solution of 1,1-bis(4-fluorophenyl)ethene (43.2 parts) in the solution was stirred at 40°C, and bromine (18.8
part) over 25 minutes, then 30% hydrogen peroxide solution (11.5 parts) was added. Testing revealed 23% residual alkenes. Further peroxide solution (24
part) was added to reduce the level of residual alkene to 14% and the reaction was completed by addition of bromine (4.7 parts). The mixture was cooled to 20°C and poured slowly into cold water (800ml) to form white crystals. Filtration and air drying yielded the crude product (61.2 parts), which was 94% 1,1-bis(4-fluorophenyl)-2-bromoethanol (by HPLC).
[Conversion rate: 91.9% based on 1,1-bis(4-fluorophenyl)ethene] Example 6 1-(2-fluorophenyl)-1-(4-fluorophenyl)-2- Bromoethanol 1-(2-fluorophenyl)-1-(4-fluorophenyl)ethene (64.8 parts) was suspended in a mixture of N,N-dimethylformamide (72 parts) and water (40 parts). , and the mixture was heated to 30°C.
Bromine (28.3 parts) and 30% hydrogen peroxide solution (18
) were added simultaneously over a period of 1 hour. When no residual alkene was observed in the PMR spectrum of the molten sample, the mixture was stirred for an additional 2 hours. mixture
Heat to 60°C, hold for 1 hour and drain the bottom layer. 129.1 parts of a light brown liquid was produced as tested by chromatography (HPLC), which was 1-(2-fluorophenyl)-1-(4-fluorophenyl).
-Contains 76.8 parts of 2-bromoethanol.
A sample of 1-(2-fluorophenyl)-1-(4-fluorophenyl)-2-bromoethanol purified by HPLC is an oily liquid that decomposes on heating and an accurate melting point cannot be obtained. Ta. Combustion analysis shows C53.5%; H3.6%; F12.8%; Br26.3%
It was hot. Calculated value of C ₁₄ H ₁₁ BrF ₂ O is C53.67%;
H3.54%; F12.14%; Br25.53%. pmr spectrum (CDCl ₃ /TMS) 3.2 (1H, doublet, J=
1.8Hz, _D2O exchangeable, unstable, OH peak),
4.11 (1H, doublet, J = 10.8Hz, split into two doublets, J = 1.8Hz, olefin H), 4.32 (1H, doublet, J = 10.8Hz, olefin H), 6.85-7.8
(8H, aromatic compound line).

Example 7 1-(2-chlorophenyl)-1-(4-fluorophenyl)-2-bromoethanol 1-(2-chlorophenyl)-1-(4-fluorophenyl)ethene (91.6 parts) was mixed with N,N - suspended in a mixture of dimethylformamide (485 parts) and water (270 parts) and the mixture was heated to 40<0>C.
Bromine (48.4 parts) and 30% hydrogen peroxide (30.6 parts)
(bromine) in alternating aliquots over approximately 1 hour.
3.1 parts followed by 2 parts hydrogen peroxide). After the addition was complete, the mixture was stirred overnight while the temperature was increased to 20°C.
The temperature was lowered to ~25°C. No residual alkene was detected in the test (pmr). Excess bromine was removed by addition of sodium bisulfite (5 parts). Stirring was stopped and the lower layer was separated. This yielded 136.5 parts of light brown liquid, which was determined by PMR analysis to be 1-(2-
Chlorphenyl)-1-(4-fluorophenyl)
-2-bromoethanol 84.9 parts (64.5 parts of theoretical yield)
%). pmr (CCl ₄ /
TMS) 4.15 (1H, double line, J = 10.8 Hz, Olefin H); 4.34 (1H, double line, J = 10.8 Hz, Olefin H); 4.5 (1H, broad peak, D ₂ O exchangeable, non-exchangeable) Stable, OH); 6.7-8.0 (8H, aromatic compound line).

Claims (1)

[Claims] 1 Formula: [wherein R and R ¹ are hydrogen, X is chlorine or fluorine, and Y and Z are each independently hydrogen, fluorine or chlorine, provided that Y and Z are not both hydrogen or both halogen and A is chlorine or bromine. The substituted alkene of formula [wherein R, R ¹ , X, Y and Z are as defined above] is treated with chlorine, bromine, A method for producing halohydrin, which comprises reacting with hypochlorous acid or hypobromous acid. Claim 1 wherein a substituted alkene of formula 2 is reacted with chlorine or bromine in a mixture of water and an amide solvent selected from dimethylformamide, diethylformamide and dimethylacetamide.
The method described in section. 3. The method of claim 2, wherein the reaction is carried out in the presence of hydrogen peroxide.