JPS607984B2 - Method for producing hydantoin derivatives - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing a hydanthin derivative, and more specifically, the present invention relates to a method for producing a hydanthin derivative, and more particularly, the present invention relates to a method for producing a hydanthin derivative, and more particularly, the present invention relates to a method for producing a hydanthin derivative, and more particularly, the present invention relates to a method for producing a hydanthin derivative. represents a carponyl group, acetyl group, cyano group or penzoyl group. (In the formula, R2 is an alkyl group having 1 to 4 carbon atoms,
4 alkoxyl group or halogen atom, n is 0
, 1, 2 or 3. ) with an aromatic isocyanate represented by the formula (wherein X, Y, R2 and n each have the same meaning as above) in the presence of a tertiary amine. This is a method for producing hydantoin derivatives. formula〔
The hydantoin derivative represented by m] is a new compound and is useful as agricultural chemicals, medicines, and intermediates thereof. The Q.8-unsaturated-Q-amino acid ester represented by the formula [m can be synthesized, for example, by the following method. '1) A method in which a cyanoformic acid ester represented by the formula N...C-COORI is reacted with an active methylene compound represented by the following in the presence of a titanium or tin halide, and the reaction product mixture is treated with water or an acidic aqueous solution. (See Japanese Unexamined Patent Publication No. 3143 of 1983 filed by the present applicant). A method of reacting a compound represented by the formula '2} with an active methylene compound represented by the above formula. Note that in each of the above formulas, R1, , 1-amino-1,2,2-trimethoxycarbonylethylene, 1-amino-1,2,2-triethoxycarbonylethylene, 1-amino-2,2-dimethoxycarbonyl-1-ethoxycarbonylethylene, 1
-amino-2,2-diethoxycarbonyl-1-methoxycarbonylethylene, 1-amino-2,2-diethoxycarbonyl-1-butoxycarbonylethylene, 1-amino-2,2-dipropoxycarbonyl-1-ethoxycarbonylethylene, 1-Amino-2-benzoyl-
1,2-diethoxycarbonylethylene, 1-ami/1-2-benzoyl-1,2-dimethoxycarbonylethylene, 1-amino-2-penzoyl-1-ethoxycarbonyl-2-methoxycarbonylethylene, 1-amino-
2-penzoyl-1-butoxycarbonyl-2-ethoxycarbonylethylene, 1-amino-2-penzoyl-
1-ethoxycarbonyl-2-propoxycarbonylethylene, 1-acetyl-2-amino-1,2-dimethoxycarbonylethylene, 1-acetyl-2-amino-1
・2-diethoxycarbonylethylene, 1-acetyl-
2-amino-2-butoxycarbonyl-1-ethoxycarbonylethylene, 1-acetyl-2-amino-2-ethoxycarbonyl-1-methoxycarbonylethylene,
1-acetyl-2-amino-2-butoxycarbonyl-
1-methoxycarbonylethylene, 1-amino-2-cyano-1,2-dimethoxycarbonylethylene, 1-amino-2-cyano-1,2-diethoxycarbonylethylene, 1-amino-2-cyano-1-butoxycarbonyl-2-ethoxy carbonylethylene, 1-amino-2
-cyano-1-ethoxycarbonyl-2-methoxycarbonylethylene, 1-amino-2-cyano-1-butoxycarbonyl-2-methoxycarbonylethylene, 1-amino-2.2-diacetyl-1-methoxycarbonylethylene, 1-amino-2. Examples include 2-diacetyl-1-ethoxycarbonylethylene, 1-amino-2,2-diacetyl-1-butoxycarbonylethylene, and the like. formula

Specific examples of the aromatic isocyanate represented by [0] include phenyl isocyanate, tolyl isocyanate, key J sil isocyanate, methoxyphenyl isocyanate, chlorophenyl isocyanate, dichlorophenyl isocyanate, trichlorophenyl Examples include isocyanate and bromophenyl isocyanate. Specific examples of the tertiary amine include aliphatic tertiary amines such as trimethylamine, triethylamine, triisopropylamine, and tributylamine. The reaction in this invention includes aromatic hydrocarbons such as benzene, toluene, and xylene, halogenated hydrocarbons such as methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, and chlorobenzene, ethyl ether, isopropyl ether, butyl ether, tetrahydrofuran, dioxane, etc. It is preferable to carry out the reaction by using ether or the like as a reaction solvent. The reaction method is to react with Q.8- under substantially anhydrous conditions.
Any method for bringing the unsaturated -Q-amino acid ester, aromatic isocyanate, and tertiary amine into contact can be employed, and there is no particular restriction on the order of addition of these raw materials. The amount of aromatic isocyanate used is Q・B-unsaturated-Q
-The amount of tertiary amine used is preferably 2 to 3 moles per mole of amino acid ester, and the amount of tertiary amine used is Q.8 monounsaturated -
The amount is preferably 1 to 3 mol per mol of Q-amino acid ester. The reaction temperature varies depending on the type of raw materials used, but
If the temperature is too high, the yield of the desired product will decrease, so it is generally preferable to employ a temperature in the range of 20 to 100 degrees. The reaction time is usually 0.5 to 10 hours. The hydantoin derivative produced by the reaction can be isolated, for example, by the following method. If the desired hydantoin derivative is precipitated as crystals from the reaction mixture, the tertiary amine can be removed by filtering the reaction mixture or by adding an acid such as hydrochloric acid or sulfuric acid. The desired product can be obtained by transferring it to water as a salt and then filtering it in an oven. When the desired hydantoin derivative is dissolved in the organic solvent, the organic solvent and the tertiary amine are removed from the reaction product mixture by a known method such as distillation, taking advantage of the difference in boiling points, and then the product is obtained. After removing the tertiary amine as a salt of these acids by taking advantage of the difference in solubility from the product, or by washing the reaction product mixture with an acid such as hydrochloric acid or sulfuric acid, the organic compound can be extracted by a known method such as distillation. By removing the solvent and utilizing the difference in solubility from the resulting product, the desired product, a hydantoin derivative, can be obtained. Specific examples of the hydantoin derivative represented by the formula [m] obtained by this invention include 5-di(ethoxycarbonyl)methylene-3-fuconinylhydantoin, 5-di(ethoxycarbonyl)methylene-3
-(p-tolyl)hydantoin, 5-di(ethoxycarbonyl)methylene-3-(p-chlorophenyl)hydantoin, 5-di(ethoxycarbonyl)methylene-3-
(2,5-dichlorophenyl)hydantoin, 5-di(
ethoxycarbonyl)methylene-3-(3,5-dichlorophenyl)hydantoin, 5-di(methoxycarbonyl)methylene-3-phenylhydantoin, 5-di(
methoxycarbonyl)methylene-3-(3,5-dichlorophenyl)hydantoin, 5-di(benzoyl)ethoxycarbonylmethylene-3-phenylhydantoin,
5-(benzoyl)ethoxycarbonylmethyleso 3-
(2,5-dichlorophenyl)hydantoin, 5-(benzoyl)ethoxycarbonylmethylene-3-(2,4
・5-Trichlorophenyl)hydantoin, 5-(benzoyl)ethoxycarbonylmethylene-3-(p-tolyl)hydantoin, 5-(benzoyl)ethoxycarbonylmethylene-3-(3,4-xylyl)hydantoin, 5-(benzoyl) ) Methoxycarbonylmethylene-3
-Phenylhydantoin, 5-(acetyl)ethoxycarbonylmethylene-3-phenylhydantoin, 5-(
Acetyl)ethoxycarbonylmethylene-3-(p-chlorophenyl)hydantoin, 5-(acetyl)ethoxycarbonylmethylene-3-(3,5-dichlorophenyl)hydantoin, 5-(acetyl)isopropoxycarbonylmethylene-3- (3,5-dichlorophenyl)
Hydantoin, 5-(acetyl)isopropoxycarbonylmethylene-3-(p-methoxyphenyl)hydantoin, 5-(cyano)ethoxycarbonylmethylene-3
-Phenylhydantoin, 5-(cyano)ethoxycarbonylmethylene-3-(3,5-dichlorophenyl)hydantoin, 5-(cyano)methoxycarbonylmethylene-3-(3,4-xylyl)hydantoin, 5- (cyano)methoxycarbonylmethylene-3-(3,5-dichlorophenyl)hydantoin,5-di(acetyl)
Examples include methylene-3-phenylhydantoin, 5-di(acetyl)methylene-3-(p-methoxyphenyl)hydantoin, and 5-di(acetyl)methylene-3-(3,5-dichlorophenyl)hydantoin. Next, examples will be shown. Example 1 To 20 mmol of benzene containing 5.0 mmol of 1-amino-1,2,2-triethoxycarbonylethylene (melting point 69.5-70o0) was added 1 phenyl isocyanate at room temperature.
10 benzene containing 4.9 mmol was added dropwise, and then 100% benzene containing 10.0 mmol of triethylamine was added dropwise, followed by reaction under reflux for 1 hour. The reaction product mixture was allowed to cool to room temperature, washed with 30% of 1N hydrochloric acid, and then thoroughly filtered. The solution was separated, and the aqueous layer was extracted three times with 30 parts each of chloroform. The chloroform layer was added to the benzene layer, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. After adding 20 g of isopropyl ether to the residue, it was filtered to obtain 1.59 g of crystals of 5-di(ethoxycarbonyl)methylene-3-phenylhydantoin. This was recrystallized from benzene to obtain colorless needle crystals with a melting point of 167.500. The elemental analysis values are shown below. C Day N Analysis value 58.08 4.75 8.36 Calculated value 57.83 4.85 8.43 (C
, 6 days, as 6N206) Example 2 To Z of 80 mmol of ethylene chloride containing 50.0 mmol of trimethylamine was added 20.0 mmol of 1-amino-1,2,2-triethoxycarbonylethylene at room temperature, followed by 50 mmol of phenyl isocyanate. After adding 20% of ethylene chloride containing 0 mmol, the reaction was allowed to proceed at room temperature for one hour. The reaction product mixture was concentrated under reduced pressure. After adding 60 g of isopropyl ether to the residue, it was filtered to obtain 6.74 g of crystals of 5-di(ethoxycarbonyl)methylene-3-phenylhydantoin. This was recrystallized from ethanol to obtain 5.41 kg of colorless needle-like crystals with a melting point of 165-16°C. The elemental analysis value is Example 1
It was similar to that of Example 3 10.0 mmol of 1-amino-1,2,2-triethoxycarbonylethylene and 2 of tri-n-butylamine
To 30' of ethylene chloride containing 4.9 mmol was added dropwise at room temperature 10' of ethylene chloride containing 24.9 mmol of phenyl isocyanate, and the mixture was reacted at room temperature for 24 hours. The reaction product mixture was concentrated under reduced pressure. The residue was recrystallized from ethanol to obtain 2.59 kg of colorless needle-like crystals of 5-di(ethoxycarbonyl)methylene-3-phenylhydantoin. Its elemental analysis values were similar to those in Example 1. Example 4 To 80 mmol of ethylene chloride containing 50.0 mmol of triethylamine was added 20.0 mmol of 1-amino-1,2,2-triethoxycarbonylethylene at room temperature, followed by p-
After adding 20 mmol of tyrene chloride containing 50.0 mmol of trilysocyanate, the mixture was allowed to react at room temperature for 1 hour. The reaction product mixture was treated as in Example 2,
Colorless acicular crystals of 5-di(ethoxycarbonyl)methylene-3-(p-tolyl)hydanthin (melting point 154oC)
5.69 evenings were obtained. The elemental analysis values are shown below. C day N analysis value 5
8.87 5.18 7.88 Calculated value 58
．． 96 5.24 8.09 (C, 7th, 8th
Example 5 Benzene 70' containing 10.0 mmol of 1-amino-1,2,2-triethoxycarbonylethylene was added at room temperature to benzene 5' containing 20.0 mmol of triethylamine, and then p -Chlorophenyl isocyanate 20
．． Add dropwise 30 g of benzene containing 0 mmol, after which
The reaction was carried out under reflux for 5 hours. The reaction product mixture was cooled to room temperature, washed with 30 portions of 1N hydrochloric acid, and the benzene layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. 25 grams of petroleum benzine was added to the remaining light brown crystals and filtered to obtain 3.70 grams of crystals of 5-di(ethoxycarbonyl)methylene-3-(p-chlorophenyl)hydantoin. This was recrystallized with ethanol to obtain 2.00 crystals with a melting point of 161.5-160. The elemental analysis values are shown below. C day N CI analysis value 52.28 4.15 7.55 9
．． 82 calculated value 52.40 4.12 7.64
9.67 (C, 6 days, as 5CIN206) Example 6 In 80' of ethylene chloride containing 50.0 mmol of triethylamine, 20.0 mmol of 1-amino-1.2.2-triethoxycarbonylethylene at room temperature; Then 3.
After adding 50.0 mmol of 5-dichlorophenyl isocyanate, the mixture was allowed to react for 2 hours at room temperature under Nada Ocean. The reaction product mixture was concentrated under reduced pressure. After adding 30 ml of ethanol to the residual liquid, heat it in a furnace and boil it for 5-5 minutes.
5.63 crystals of di(ethoxycarbonyl)methylene-3-(3,5-dichlorophenyl)hydanthin were obtained. This was recrystallized from ethanol and had a melting point of 172-173.
4.19 colorless needle-like crystals of 0.00 were obtained. The elemental analysis values are shown below. C day N CI analysis value 48.11 3.73 6.97 17
．． 56 calculated value 47.90 3.52 6.98
17.67 (C, 6 days, as 4CI2N206) Example 7 1-Amino-2-penzoyl-1,2-diethoxycarbonylethylene (mp 138-13900) was added to 30' of benzene containing 10.0 mmol at room temperature. , 10 parts of benzene containing 20.0 mmol of triethylamine, and then 15 parts of benzene containing 25.0 mmol of p-tolylisocyanate were added dropwise, and the mixture was reacted under a rope at room temperature for 20 hours. The reaction product mixture was heated in a furnace, and the furnace liquid was concentrated under reduced pressure. Add 30% of isopropyl ether to the residue and filter it.
2.74 crystals of 5-(benzoyl)ethoxycarbonylmethylene-3-(p-tolyl)hydantoin were obtained.
This was recrystallized from ethanol and the melting point was 205-20o.
2.07 days of pale yellow needle crystals were obtained. The elemental analysis values are shown below. C Day N Analyzed value 66.80 4.87 7.41 Calculated value 66.66 4.79 7.40 (C
Example 8 To benzene containing 10.0 mmol of 1-acetyl-2-amino-1,2-ditoxycarbonylethylene (melting point 88-8900) was added 20.0 mmol of triethylamine at room temperature.
of benzene containing 25.0 mmol of benzene, then of benzene containing 25.0 mmol of phenylisocyanat.
was added dropwise, and the mixture was allowed to react for 2 hours at room temperature. The reaction product mixture was treated as in Example 7,
Pale yellow needle crystals of 5-(acetyl)ethoxycarponylmethylene-3-phenylhydanthin (melting point 16,200
) 1.60 evenings were obtained. The elemental analysis values are shown below. C Day N Analysis value 59.68 4.68 9.28 Calculated value 59.60 4467 9.27 (C
, 5 days, 4N205) Example 9 1-acetyl-2-amino-2-ethoxycarbonyl-
1-isopropoxycarbonylethylene (melting point 64-6
600) Benzene 15 containing 5.0 mmol and benzene 15 containing 10.0 mmol triethylamine at room temperature, followed by p-methoxyphenyl isocyanate 1
10' of benzene containing 2.5 mmol was added dropwise, and the reaction was allowed to proceed at room temperature for 24 hours under pressure. The reaction product mixture was processed in the same manner as in Example 6 to yield 5-(acetyl)isof. Pale yellow crystals of lopoxycarbonylmethylene-3-(p-methoxyphenyl)hydanthin (melting point 168-170
00) Obtained 0.83 evening. The elemental analysis values are shown below. C Day N Analysis value 59.04 5.12 8.00
Calculated value 58.95 5.24 8.09
(as C, 7 days, 8N206) Example 10 To 30 mmol of benzene containing 5.0 mmol of 1-amino-2-cyano-1,2-diethoxycarbonylmethylene (melting point 76-77q0) was added 10 mmol of triethylamine at room temperature.
15 benzene containing 0 mmol and then 15 benzene containing 14.2 mmol of phenyl isocyanate were added dropwise, and the mixture was allowed to react under the brood frame at room temperature for 2 hours. To the reaction product mixture, 14.5 parts of 1N hydrochloric acid and 15.5 parts of water were added under ice-cooling, and then heated in the oven to give 1.449 parts of 5-(cyano)ethoxycarbonylmethylene-3-phenylhydanthin. Obtained. This was recrystallized from ethanol and had a melting point of 234-2360.
1.10 pale yellow needle crystals of 0.0% were obtained. The elemental analysis values are shown below. C Day N Analysis value 59.16 4.02 14.63
Calculated value 58.95 3.89 14.73 (
Example 11 Triethylamine 2 was added to 40 mmol of benzene containing 10.0 mmol of 1-amino-212-diacetyl-1-ethoxycarbonylethylene (melting point 75-7600) at room temperature.
Benzene 10 containing 0.0 mmol followed by Benzene 10 containing 20.0 mmol phenyl isocyanate.
After dropping the mixture, the reaction mixture was allowed to react for 2 hours at room temperature under a coagulation frame. Add 20 parts of 1N hydrochloric acid and 1 part of water to the reaction mixture under ice cooling.
5-di(acetyl)methylene-
2.54 ml of 3-phenylhydantoine was obtained. This was recrystallized from benzene to obtain pale yellow needle crystals with a melting point of 230 to 23 years C (1.75 mm). The elemental analysis values are shown below. C Day N Analysis value 62.04 4.55 10.30 Calculated value 61.76 4.44 10.29 (C
, 4 days, as 2N204) Example 12 15 benzene containing 5.0 mmol of 1-amino-2,2-diacetyl-1-ethoxycarbonylethylene,
At room temperature, 5' of benzene containing 10.0 mmol of p-methoxyphenylisocyanate and then 10' of benzene containing 12.5 mmol of p-methoxyphenylisocyanate were added dropwise, followed by the addition of a The reaction mixture was allowed to react for 24 hours.
I got the evening. This was recrystallized from ethanol, with a melting point of 221-22°C.
Yellow needle-like crystals of 0.84 mm were obtained. The elemental analysis values are shown below. C Day N Analyzed value 59.55 4.86 9.29 Calculated value 59.60 4.67 9.27 (C,5
Example 13 To 100' of benzene containing 50.2 mmol of 1-amino-2,2-diacetyl-1-ethoxycarbonylethylene was added 50' of benzene containing 100.4 mmol of triethylamine at room temperature. After dropping 100.4 mmol of 315-dichlorophenyl isocyanate, the mixture was reacted for 18 hours at room temperature under a coagulation frame. To the reaction product mixture, 50% of 2N hydrochloric acid was added under ice, filtered, and 5-di(acetyl)methylene-3-(3.5
12.96 crystals of hydantoin (dichlorophenyl) were obtained. The crystals were recrystallized with benzene to give a melting point of 25.
1.18 pale yellow needle crystals of 4 to 255 ounces were obtained. The elemental analysis values are shown below. C day N
CI analysis value 49.47 2.81 8.08
21.05 Calculated value 49.29 2.95 8.
21 20.78 (C, 4th,.

Claims (1)

[Claims] 1 Formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 represents an alkyl group having 1 to 4 carbon atoms, and
and Y each represent an alkoxycarbonyl group having 2 to 5 carbon atoms, an acetyl group, a cyano group, or a benzoyl group. ) and the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^2 is an alkyl group with 1 to 4 carbon atoms,
~4 alkoxyl groups or halogen atoms, and n is 0, 1, 2 or 3. ) is reacted with an aromatic isocyanate represented by the following formula in the presence of a tertiary amine. A method for producing a hydantoin derivative represented by the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (wherein, X, Y, R^2 and n each have the same meanings as above).