JPS607986B2 - Method for producing 5-(alkoxycarbonyl)methylenehydantoins - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing 5-(alkoxycarbonyl)methylenehydantoins, which are novel compounds. More specifically, this invention relates to the formula (where RI and R2 each represent an alkyl group having 1 to 4 carbon atoms, and X represents an alkoxycarbonyl group having 2 to 5 carbon atoms, a benzyl group, or a cyano group). ) is reacted with phosgene or trichloromethyl chloroformate in the presence of pyridine, and then the reaction product is converted into a compound of the formula R3NH2 where R3 is a hydrogen atom, an alkyl group having 1 to 7 carbon atoms,
Alkenyl group having 3 to 7 carbon atoms, cycloalkyl group having 5 to 7 carbon atoms, benzyl group (wherein R4 is a hydrogen atom, an alkyl group having 1 to 7 carbon atoms, an alkoxyl group having 1 to 4 carbon atoms, a halogen Represents an atom or nitro group, n is 0, 1
, 2 or 3. ) represents a group. 5-(alkoxycarbonyl)methylenehydantoins represented by the formula (wherein R2, R3 and x each have the same meanings as above), which are reacted with a primary amine represented by This is the manufacturing method. In this invention, the reaction is thought to proceed as shown in the following formula. A method is known in which esters of Q-amino acids such as glycine and alanine are reacted with phosgene to produce isocyanates of Q-amino acids, and then amines are reacted with this to obtain hydantoin derivatives (Kirkosmer, E. Cyclopedia of Chemical Technology, 2nd Edition, Volume 11, Pages 141-164,
(1966). A known method is used to prepare Q.8-unsaturated-Q represented by formula [1]
- Even when applied to amino acid esters, 5-(alkoxycarponyl)methylenehydantoins represented by formula [m] cannot be obtained. In the first step, the Q.8-unsaturated Q-amino acid ester represented by the formula [1] is reacted with phosgene or chloroformic acid trichloromethyl ester in the presence of pyridine, and then the reaction product is the expression

By reacting with amines represented by [0], 5-(alkoxycarbonyl) represented by formula [m]
This is based on the knowledge that methylene hydantoins can be obtained. The 5-(alkoxycarbonyl)methylenehydantoins obtained by this invention are new compounds and are useful as agricultural chemicals, medicines, and raw materials thereof. Formula [1
] The Q.8-unsaturated-Q-amino acid ester represented by the formula can be synthesized, for example, by the following method. {1} A cyanoformate ester represented by the formula N:C-COORI and an active methylene compound represented by the formula are reacted in the presence of a titanium or tin halide, and the reaction product mixture is treated with water or an acidic aqueous solution. Method (see Japanese Patent Application Laid-Open No. 103143/1983 filed by the present applicant). {2) A method of reacting a compound represented by the formula with an active methylene compound represented by the above formula. In addition, in each of the above formulas, R1, R2 and X are respectively the same as defined in formula [1]. Specific examples of the Q-8-unsaturated-Q-amino acid ester represented by formula [1] include 1-amino-1,2,2-trimethoxycarbonylethylene, 1-amino-1,2,2-triethoxy carbonylethylene, 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-penzoyl-1,2-diethoxycarbonylethylene, 1-amino-2-penzoyl-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-amino-2-cyano-112-dimethoxycarbonylethylene, 1-amino-2-cyano 1.
2-diethoxycarbonylethylene, 1-amino-2-
Cyano-1-butoxycarbonyl-2-ethoxycarbonylethylene, 1-amino-2-cyano-1-ethoxycarbonyl-2-methoxycarbonylethylene, 1-amino-2-cyano-1-ptoxycarbonyl-2-methoxycarbonylethylene, etc. can be mentioned. Specific examples of the primary amine represented by formula [B] include ammonia, methylamine, ethylamine, propylamine, butylamine, cyclohexylamine, allylamine, benzylamine, aniline, toluidine, xylidine, anisidine, chloroaniline, dichloroaniline,
Examples include trichloroaniline, nitroaniline, nitroanisidine, and chlorotoluidine. Next, the reaction method in this invention will be explained. '1} Q represented by formula [1] in the presence of pyridine
Reaction of 8-monounsaturated -Q-amino acid ester with phosgene or chloroformic acid trichloromethyl ester: This reaction is carried out with aromatic hydrocarbons such as benzene, toluene, xylem, methylene chloride, chloroform, carbon tetrachloride, ethylene chloride, etc. Preferably, the reaction is carried out in an organic solvent such as a halogenated hydrocarbon. There are no particular restrictions on the amount of reaction solvent used, but usually
The amount is 5 to 10 parts by weight per part by weight of the 6-unsaturated-Q-amino acid ester represented by formula [1]. There is no particular restriction on the order of addition of raw materials, but Q.8-unsaturated-
It is convenient to add a solution of phosgene or chloroformic acid trichloromethyl ester in an organic solvent to a solution or suspension in an organic solvent containing the Q-amino acid ester and pyridine. The amount of Q.6-unsaturated-Q-amino acid ester used is preferably 0.75 to 1 mol per mol of phosgeso, and 0.4 to 0.5 mol per mol of trichloromethyl chloroformate. . The amount of pyridine used is preferably about 2 moles per mole of phosgene and about 4 moles per mole of trichloromethyl chloroformate. The reaction temperature is preferably 4,000 or lower, particularly 0 to 3,000, from the viewpoint of suppressing side reactions. The reaction time is usually 0.5 to 4 hours. The reaction product mixture is expressed as follows:

It can be subjected to a reaction with a primary amine represented by [0]. If desired, the reaction product may be isolated from the reaction product mixture and subjected to reaction with the primary amine. ■ Reaction products and formulas

Reaction with a primary amine represented by [0]: the above {1
} is added to the reaction product mixture or a solution or suspension of the reaction product in an organic solvent, and the primary amine represented by formula m] is added, and the reaction is usually carried out at a temperature of 0 to 10,000°C. formula

The amount of the primary amine represented by [0] used is preferably 1 to 1.5 mol per 1 mol of phosgene when phosgene is used in the reaction of m above; When methyl ester is used, it is preferably used in an amount of 2 to 3 moles per mole of trichloromethyl chloroformate. The reaction time is usually 1-2 beat hours. In this reaction, when alkylamine, cycloalkylamine, alkenylamine, benzylamine, alkoxyphenylamine, etc. are used as the primary amine,
Along with the 5-(alkoxycarbonyl)methylenehydantoins represented by the formula [m], the hydantoic acid esters represented by the above formula [W], which are precursors thereof, may be obtained. At this time, hydantoate esters are prepared by adding a tertiary amine such as triethylamine, tripropylamiso, or tributylamine to the reaction product mixture or the above-mentioned hydantoate esters isolated from the reaction product mixture and heating the mixture. It can be converted into a 5-(alkoxycarbonyl)methylenehydantoin represented by formula [m] by ring closure. The desired product, 5-(alkoxycarbonyl)methylenehydantoin, can be isolated, for example, by the following method. The reaction product mixture is washed with water to remove the pyridinium chloride by-produced in the above reaction as an aqueous solution, and then the organic solvent is distilled off to obtain crude crystals of the desired product. Crude crystals of the desired product are isolated by conventional methods of preparation. Specific examples of 5-di(methoxycarbonyl)methylene-3-isopropylhydantoin, 5-di(methoxycarbonyl)methylene- 3-penzylhydantoin, 5-di(methoxycarbonyl)methylene-3-(315-dichlorophenyl)hydantoin, 5-di(ethoxycarbonyl)
Methylene-3-phthylhydantoin, 5-di(ethoxycarbonyl)methylene-3-cyclohexylhydantoin, 5-di(ethoxycarbonyl)methylene-3-allylhydantoin, 5-di(ethoxycarbonyl)methylene-3-phenylhydantoin , 5-di(ethoxycarbonyl)methylene-3-(p-tolyl)hydantoin,
5-di(ethoxycarbonyl)methylene-3-(305
-dichlorophenyl)hydantoin, 5-di(ethoxycarbonyl)methylene-3-(2,4,5-trichlorophenyl)hydantoin, 5-di(ethoxycarbonyl)methylene-3-(2-methoxy-4-nitrophenyl) ) Hydantoin, 5-di(propoxycarbonyl)methylene-3-methylhydantoin, 5-(benzoyl)ethoxycarbonylmethylene-3-isopropylhydantoin, 5-(benzoyl)ethoxycarbonylmethylene-3-phthylhydantoin, 5-( Benzoyl)ethoxycarbonylmethylene-3-allylhydantoin, lye
(benzoyl)ethoxycarbonylmethylene-3-(3
・4-xylyl)hydantoin, 5-(benzoyl)ethoxycarbonylmethylene-3-(2,4,5-trichlorophenyl)hydantoin, 5-(benzoyl)ethoxycarbonylmethylene-3-(3,5-dichlorophenyl) ) Hydantoin, 5-(benzoyl)propoxycarbonylmethylene-3-penzylhydantoin, 5-(
benzoyl)propoxycarponylmethylene-3-(4
-methoxyphenyl)hydantoin, 5-(benzoyl)methoxycarbonylmethylene-3-phenylhydantoin, 5-(cyano)ethoxycarbonylmethylene-3
-isopropylhydantoin, 5-(cyano)ethoxycarbonylmethylene-3-allylhydantoin, 5-(
cyano)ethoxycarbonylmethylene-3-(3.5-
dichlorophenyl)hydantoin, 5-(cyano)methoxycarbonylmethylene-3-isopropylhydantoin, 5-(cyano)methoxycarbonylmethylene-3-(3,4-xylyl)hydantoin, 5-(cyano)methoxycarbonylmethylene-3-( Examples thereof include 3,5-dichlorophenyl)hydantoin and 5-[(benzoyl)ethoxycarbonylmethylene]hydantoin. Next, examples will be shown. Example 1 1-Amino-2,2-dimethoxycarbonyl-1-ethoxycarbonylethylene (melting point 72-73°C) 80.7
20 mmol of methylene chloride containing 107.5 mmol of phosgene was added dropwise to 120 mmol of methylene chloride containing 193.6 mmol of pyridine under ice-cooling, and the mixture was allowed to react at room temperature for 2 hours under reduced pressure. To the reaction mixture was added dropwise 60 methylene chloride containing 80.7 mmol of 3,5-dichloroaniline under ice cooling, and the mixture was allowed to react at room temperature for 2 hours under condensation. 150 m' of water was added to the resulting reaction product mixture and then filtered. The furnace solution was separated, and the organic solvent layer was dried over hot sodium sulfate and then concentrated under reduced pressure. By adding 50% of ethanol to the residual sticky crystals and filtering, 16.34% of 5-di(methoxycarbonyl)methylene-3-(3,5-dichlorophenyl)hydanthin was obtained as crystals. Ta. By recrystallizing this crystal with ethanol,
7.27 colorless needle crystals with a melting point of 228-23,000 were obtained. The elemental analysis values (unit: weight %, same hereinafter) are shown below. C day N CI analysis value 45.38 2.41 7.57 19
．． 21 calculated value 45.06 2.70 7.51
19.00 (C, 4 days, as N206CI2) Example 2 Contains 11.0 mmol of 1-amino-1,2,2-triethoxycarbonylethylene (melting point 69.5-7000) and 26.3 mmol of pyridine. Benzene 1 containing 13.2 mmol of phosgene in 40' of benzene under ice cooling
0' was added dropwise to the mixture, and the mixture was allowed to react for 2 hours at room temperature. To the reaction mixture was added dropwise 10 drops of benzene containing 15.4 mmol of aniline under ice cooling, and the reaction mixture was allowed to react under reflux for 3 minutes. 30 g of water was added to the reaction product mixture and then filtered. The furnace solution was separated, and the organic solvent layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. By adding 30% of isopropyl ether to the residual crystals and filtering, 2.33% of 5-di(ethoxycarbonyl)methylene-3-phenylhydantoin was obtained. By recrystallizing this with benzene, colorless needle-like crystals with a melting point of 167.500 were obtained. The elemental analysis values are shown below. C Day N Analysis value 57.94 4.85 8.23 Calculated value
57.83 4.85 8.43 (C, 6th, 6N
206) Example 3 35 mmol of benzene containing 13.6 mmol of 1-amino-1,2,2-triethoxycarbonylethylene and 32.6 mmol of pyridine, under ice, containing 16.3 mmol of phosgene. 15% of benzene was added dropwise to the mixture, and the mixture was allowed to react at room temperature for 2 hours. To the reaction mixture was added dropwise 15 parts of benzene containing 19.0 mmol of p-toludine under ice cooling, and the reaction mixture was allowed to react at room temperature for 1 hour under condensation. The reaction product mixture was treated as in Example 2 to give 5.07 kg of red oak crystals as a concentrated residue. By recrystallizing the residual liquid with 70 volumes of ethanol, 5-
1.92 g of di(ethoxycarbonyl)methylene-3-(p-tolyl)hydanthin (melting point 154-155 DEG C.) was obtained. The elemental analysis values are shown below. C Day N Analysis value 58.81 5.13 7.91 Calculated value
59.96 5.24 8.09 (C, 7th, 8N
206) Example 4 Phosgene 26 was added under ice-cooling to 60 methylene chloride containing 20.0 mmol 1-amino-1,2,2-triethoxycarponylethylene and 48.0 mmol pyridine.
．． 10 M of methylene chloride containing 2 mmol was added dropwise to the mixture, and the mixture was reacted for 3 hours at room temperature under vacuum. The reaction product mixture was added with 30 methylene chloride containing 20.0 mmol of 3,5-dichloroaniline under ice cooling.

[ was added dropwise to the mixture, and the mixture was allowed to react at room temperature for 1 hour under a glass of water. The reaction product mixture was treated as in Example 1,
5-di(ethoxycarbonyl)methylene-3-(3.5
-Dichlorophenyl)hydantoin colorless crystals (melting point 1
72-175q○) 1.42 evenings were obtained. The elemental analysis values are shown below. C day N CI analysis value 48.00 3.83 6.79 17.
49 calculated value 47.90 3.52 6.98 1
7.67 (C, 6th, 4CI2N206) Example
5 To 35' of methylene chloride containing 13.1 mmol of 1-amino-1,2,2-triethoxycarbonylethylene and 31.4 mmol of pyridine, 1 phosgene was added under ice cooling.
15 of methylene chloride containing 5.8 mmol was added dropwise,
The reaction mixture was allowed to react for 2 hours at room temperature under a vacuum cleaner. To the reaction product mixture, 20 methylene chloride containing 18.3 mmol of 2,4,5-trichloroaniline was added dropwise under ice cooling, and the mixture was allowed to react under a pestle at room temperature for 1 hour. The reaction product mixture was treated as in Example 1,
5-di(ethoxycarbonyl)methylene-3-(2.4
・Colorless crystals of 5-trichlorophenyl)hydanthin (
A melting point of 172-17400) was obtained. The elemental analysis values are shown below. C day N
CI analysis value 44.18 2.70 6.26 24
．． 34 calculated value 41.11 3.01 6.43
24.41 (C, 6 days, 3C] as 3N206) Example 6 To 35M of benzene containing 3.0 mmol of 1-amino-112,2-triethoxycarbonylethylene i and 31.1 mmol of pyridine was added phosgene under ice cooling. 15.1 mmol of benzene containing 15.6 mmol was added dropwise, and the reaction was allowed to proceed at room temperature for 2 hours.To the reaction product mixture, 18.1 mmol of 4-nitro-0-anisidine was added under ice-cooling. The reaction mixture was allowed to react for 1 hour at room temperature.The reaction product mixture was treated as in Example 1,
Crystals of 5-di(ethoxycarbonyl)methylene-3-(2-methoxy-4-nitrophenyl)hydanthin (melting point: 170-17,200) were obtained in an amount of 0.68 kg. The elemental analysis values are shown below. C Day N Analysis value 50.06 4.44 10.09 Calculated value 50.13 4.21 10.32 (C, 7th day,
7N309) Example 7 36.3 mmol of phosgene was added under ice cooling over 25 mmol of methylene chloride containing 30.2 mmol of 1-amino-2-penzoyl-112-diethoxycarbonylethylene (mp 138-13900) and 726 mmol of pyridine. Add 25 mmol of methylene chloride containing 25 mmol of
Allowed time to react. 42. 3,4-xylidine was added to the reaction product mixture under ice.
25 units of methylene chloride containing 3 mmol was added dropwise to the mixture, and the reaction was allowed to proceed for 1 hour at room temperature under a vacuum cleaner. The reaction product mixture was treated as in Example 2 except that ethanol was used as the recrystallization solvent to give 5-(
benzoyl)ethoxycarbonylmethylene-3-(3.
Cool-colored needle-like crystals of 4-xylyl)hydantoin (melting point 19
5-197°C) 4.29 hours were obtained. The elemental analysis values are shown below. C Day N Analysis value 67.28 5.17 7.05 Calculated value
67.34 5.14 7.14 (C22nd 2bu2
Example 8 40.2 mmol of 1-amino-2-benzoyl-1,2-diethoxycarbonylethylene and 96.0 mmol of pyridine.
To 75 mmol of methylene chloride containing 5 mmol, 30 mmol of methylene chloride containing 48.2 mmol of phosgene was added dropwise under ice cooling, and the mixture was reacted at room temperature for 2 hours. To the reaction product mixture, 25 methylene chloride containing 56.3 mmol of 3,5-dichloroaniline was added dropwise under ice cooling, and a reaction was carried out at room temperature under water. The reaction product mixture was treated as in Example 1 except that benzene was used as the recrystallization solvent to give a slightly yellow 5-(benzoyl)ethoxycarbonylmethylene-3-(3,5-dichlorophenyl)hydasotoine. Needle crystals (melting point 249-2
5100) 5.91 evening was obtained. The elemental analysis values are shown below. C day N CI analysis value 55.
06 3.25 6.38 16.06 Calculated value
55.45 3.26 6.47 16.37 (
Example 9 43.3 mmol of 1-amino-2-penzoyl-1,2-diethoxycarbonylethylene and 103 pyridiso
．． In 70' of methylene chloride containing 9 mmol, under ice cooling,
30' of methylene chloride containing 52.0 mmol of phosgene
was added dropwise, and the mixture was allowed to react for 2 hours at room temperature under a pestle. Fifty units of methylene chloride containing 60.6 mmol of 2,4,5-trichloroaniline were added dropwise to the reaction mixture under ice cooling, and the reaction mixture was allowed to react at room temperature under a cicada atmosphere for 10 hours. The reaction product mixture was treated as in Example 1 except that benzene was used as the recrystallization solvent to obtain 5-(benzoyl)ethoxycarbonylmethylene-3-(2.4
・Colorless crystals of 5-trichlorophenyl)hydanthin (
A melting point of 50-25 was obtained. The elemental analysis values are shown below. C day N
CI analysis value 51.47 2.89 5.94
22.97 Calculated value 51.36 2.80 5.9
9 1 22.74 (as C2 Rainbow, 3CI3N205) Example 10 Methylene chloride 60 containing 20.0 mmol of 1-amino-2-cyano 1,2-diethoxycarbonylethylene (mp 76-7700) and 48.0 mmol of pyridiso
Then, under ice, 20 methylene chloride containing 25.4 mmol of phosgene was added dropwise to the mixture, and then the mixture was poured into the solution and allowed to react at room temperature for 2 hours. To the reaction product mixture, 20 mmol of methylene chloride containing 20.0 mmol of 3,5-dichloroaniline was added dropwise under ice cooling, and the reaction mixture was allowed to react for 1 hour at room temperature under cooling conditions. 100% water was added to the reaction product mixture, which was then filtered to give 5-(cyano)ethoxycarbonylmethylene-3-(
1.64 ml of 3,5-dichlorophenyl)hydantoin was obtained. Separate the furnace liquid, concentrate the organic solvent layer under reduced pressure,
5.23 hours of brown solid was obtained as residual sugar. 50% of ethanol was added to this residue, which was then filtered to obtain 1.50% of the above compound. The total amount of the above compound (3.14) was recrystallized from ethyl acetate to form colorless needle crystals (melting point 285).
~2870) Obtained 1.51 evening. The elemental analysis values are shown below. C day N CI analysis value 47.76 2.56 11.82 19
．． 88 calculated value 47-48 2.56 11.87
20.02 (C, 4 days as 9CI2N304) Example 11 1-amino-2-cyano 1-ethoxycarbonyl-2
-Methoxycarbonylethylene (melting point 115-1160
0) Add 177% of phosgene to 60% of methylene chloride containing 14.7 mmol and 35.4 mmol of pyridine under ice cooling.
15 mmol of methylene chloride was added dropwise to the mixture, and the mixture was reacted for 2 hours at room temperature under a rope. Add 20% of 3,4-xylidine to the reaction mixture under ice cooling.
25 mmol of methylene chloride containing 6 mmol was added dropwise and allowed to react for 1 hour at room temperature under the ocean. 50 sakaki of water was added to the reaction product mixture, and then it was filtered. The reaction mixture was separated into organic solvent layers. After drying with anhydrous sodium sulfate, it was concentrated under reduced pressure and the residue was 3.9 g of yellow crystals.
I got 5 nights. Add 20% of ethanol to this, and then heat in a furnace to crystallize 2.1 of 5-(cyano)methoxycarbonylmethylene-3-(3,4-xylyl)hydanthin.
I got 2 nights. The crystals were recrystallized from methanol to obtain yellow needle crystals with a melting point of 255-2570. The elemental analysis values are shown below. C Day N Analysis value 60.48 4.20 14.33 Calculated value 60.20 4.38 14.04 (C, 5th day,
3N304) Example 12 1-Amino-2-cyano-1-ethoxycarbonyl-2
- 60 mmol of methylene chloride containing 25.0 mmol of methoxycarbonylethylene and 59.9 mmol of pyridine
To the mixture was added dropwise 10 methylene chloride containing 33.6 mmol of phosgene under ice-cooling, and the mixture was allowed to react at room temperature for 2 hours under reduced pressure. Add 3,5-dichloroanie IJ to the reaction product mixture under ice cooling.
30 methylene chloride containing 25.0 mmol of chloride was added dropwise to the mixture, and the reaction was carried out at room temperature under a punch. The reaction product mixture was treated as in Example 10 to give 5-(cyano)methoxycarbonylmethylene-3-(
1.159 pale yellow crystals (melting point 268-269o0) of 3,5-dichlorophenyl)hydanthin were obtained. The elemental analysis values are shown below. C day N C
I Analysis value 46.00 2.04 12.32 20
．． 46 calculated value 45.91 2.07 12.35
20.85 (C, 3 days as 7CI2N304) Example 13 120 m of chlorobenzene containing 14.9 mmol of 1-amino-2-penzoyl-1,2-diethoxycarbonylmethylene (mp 138-13900) and 32.7 mmol of pyridine. 30 drops of chlorobenzene containing 16.4 mmol of phosgene were added under the ice, and 2 drops of soil were added under the ice.
Allowed time to react. To the reaction product mixture, 5.96 g of a 2% by weight aqueous solution of ammonia was added dropwise under ice cooling, and the mixture was allowed to react for 3 hours under simulated ammonia. 50' of water was added to the reaction product mixture, then filtered,
0.74 crystals of 5-(benzoyl)ethoxycarbonylmethylenehydantoin were obtained. This was recrystallized from ethanol, with a melting point of 229-231°C.
0.43 hours of cool-colored needle-like crystals were obtained. The elemental analysis values are shown below. C Day N Analysis value 58.40 4.28 9.65 Calculated value
58.33 4.20 9.72 (C, 4 days.2N
205) Example 14 1-Amino-2,2-dimethoxycarbonyl-lmethoxycarbonylethylene (melting point 72-73°C) 60.0
To 110 mmol of methylene chloride containing 144.0 mmol of pyridine, 10 mmol of methylene chloride containing 75.7 mmol of phosgene was added dropwise under ice-cooling, and the mixture was allowed to react at room temperature for 2 hours under a syringe. 60% of isopropylamine was added to the reaction mixture under ice cooling.
30 M of methylene chloride containing 1 mmol was added dropwise, and the mixture was allowed to react at room temperature for 2 hours. After adding 100% of water to the reaction product mixture, the liquid was separated,
The organic solvent layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. 100 M of benzene containing 18.7 mmol of triethylamine was added to the residue, and the mixture was reacted under reflux for 3 hours. The reaction product mixture was concentrated under reduced pressure, and the residual crystals were recrystallized from ethanol to give 5-di(methoxycarponyl)methylene-3-isoph. Colorless acicular crystals of lopyrhydantin (melting point 128-12
900) Obtained on 3.10 pm. The elemental analysis values are shown below. C Day N Analyzed value 48.78 5.12 10.28 Calculated value 48.89 5.22 10.37 (C,.day,
4N206) Example 15 1-Amino-2,2-dimethoxycarbonyl-1-ethoxycarbonylethylene and 100 methylene chloride containing 30.0 mmol of pyridine and 72.1 mmol of pyridine,
Under ice-cooling, 25 mmol of methylene chloride containing 35.7 mmol of phosgene was added dropwise, and the mixture was allowed to react at room temperature for 2 hours under reduced pressure. To the reaction mixture was added dropwise 25' of methylene chloride containing 30.1 mmol of benzylamiso under ice-cooling.
The reaction was allowed to proceed at room temperature for 24 hours. After adding 5 parts of water to the reaction product mixture, the layers were separated, and the organic solvent layer was dried over anhydrous sodium sulfate, and then concentrated. 200% of isopropyl ether was added to the residue, and then heated to give 5-di(methoxycarbonyl)methylene-
1.50 crystals of 3-penzylhydanthin were obtained. The isopropyl ether solution of the furnace liquid was concentrated, and 50 benzene containing 39.5 mmol of triethylamine was added to the residue, and the mixture was reacted under reflux for 1.5 hours. Thereafter, benzene was distilled off to crystallize 5-di(methoxycarbonyl)methylene-3-penzylhydantoin.
I got 78 evenings. This crystal and the above crystal were recrystallized with methanol to give colorless needle-shaped crystals with a melting point of 169-171°C.2.
I got 32 evenings. The elemental analysis values are shown below. C Day N Analysis value 56.56 4.39 8.75 Calculated value
56.61 ・4.43 8.80 (C, 5th, 4N
206) Example 16 Methylene chloride 3 containing 11.8 mmol of 1-amino-1,2,2-triethoxycarbonylethylene (Fumushi point 69.5-7000) and 28.3 mmol of pyridine.
15 M of methylene chloride containing 14.2 mmol of phosgene was added dropwise to the solution under ice-cooling, and the mixture was reacted for 2 hours at room temperature under Nada. To the reaction mixture was added dropwise 10 volumes of methylene chloride containing 16.5 mmol of butylamine under ice cooling, and the mixture was reacted for one period at room temperature under a hawker. The reaction product mixture was treated as in Example 14 except that n-hexane was used as the recrystallization solvent to give 5
Crystals of -di(ethoxycarbonyl)methylene-3-butylhydanthin (melting point 59-61°C) at 0.96°C were obtained. The elemental analysis values are shown below. C Day N Analysis value 54.04 6.28 8.92 Calculated value
53.84 6.45 8.97 (CMH2bu20
6) Example 17 A mixture of 25 methylene chloride containing 11.1 mmol of 1-amino-1,2,2-triethoxycarbonylethylene and 26.7 mmol of pyridine was added under ice-cooling to 13 phosgene.
．． 15 ml of methylene chloride containing 3 mmol was added dropwise and allowed to react at room temperature for 2 hours. To the reaction mixture was added dropwise 10 methylene chloride containing 15.6 mmol of allylamine under ice-cooling, and
The reaction was carried out under reflux for 2 hours. The reaction product mixture was treated as in Example 14 to obtain colorless needle crystals of 5-di(ethoxycarbonyl)methylene-3-allylhydanthin (melting point 91-9200).
．． I got 60 evenings. The elemental analysis values are shown below. C Day N Analysis value 52.49 5.45 9.29 Calculated value
52.70 5.44 9.46 (C, 3rd, 6N
206) Example 18 47.3 mmol of 1-amino-2-penzoyl-1,2-diethoxycarbonylethylene and 113 mmol of pyridine
．． To 75 mmol of methylene chloride containing 4 mmol, 30 mmol of methylene chloride containing 56.7 mmol of phosgene was added dropwise under ice cooling, and the mixture was allowed to react under a female pestle at room temperature for 2 hours. 25 m' of methylene chloride containing 66.2 mmol of isopropylamine was added dropwise to the reaction product mixture, and the mixture was allowed to react at room temperature for 2 hours under water pressure. After adding 50 kg of water to the reaction product mixture, the layers were separated, and the organic solvent layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. 48.0 mmol of triethylamine and 50 mmol of benzene were added to the solution, and the mixture was reacted under reflux for 2 hours. The reaction product mixture was concentrated under reduced pressure, and 180 g of ethanol was added to the yellowish brown crystals of the residue, which was then filtered to obtain crystals of 5-(benzoyl)ethoxycarponylmethylene-3-1-isopropylhydanthin. I got it. Recrystallize this with ethanol and the melting point will be 160-16○
4.48 kg of colorless needle crystals were obtained. The elemental analysis values are shown below. C Day N Analysis value 61.58 5.29 8.49 Calculated value
61.81 5.49 8.48 (C, 7th, 8N
205) Example 19 1-amino-2-penzoyl-1,2-diethoxycarbonylethylene 12.7 mmol and pyridine 30.
In 25' of methylene chloride containing 6 mmol, phosgene 1
15% of methylene chloride containing 5.3 mmol was added dropwise under ice cooling, and the mixture was reacted for 2 hours at room temperature under cooling conditions. To the reaction mixture was added dropwise 10 g of methylene chloride containing 17.8 mmol of butylamine under ice, and the mixture was allowed to react at room temperature for 1 hour. After adding 30% of water to the reaction product mixture, the layers were separated, and the organic solvent layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. 12.5 mmol of triethylamine and 50 mmol of benzene were added to the remaining bamboo, and the mixture was reacted under reflux for 3 hours. The reaction product mixture was treated as in Example 18 to give 5-(besozoyl)ethoxycarbonylmethylene-3
- Pale yellow needle crystals of butylhydanthin (melting point 142~
1440C) Obtained 1.06 pm. The elemental analysis values are shown below. C Day N Analysis value 62.86 5.72 7.96 Calculated value
62.78 5.85 8.14 (C, 8th 2 states 2
05) Example 20 29.6 mmol of 1-amino-2-penzoyl-1,2-diethoxycarbonylethylene and 70.0 mmol of pyridine.
On top of 60 methylene chloride containing 9 mmol, 30 i of methylene chloride containing 35.5 mmol of phosgene was added dropwise under ice cooling, and the mixture was allowed to react at room temperature for 2 hours under condensation. To the reaction product mixture, 20 methylene chloride containing 41.3 mmol of allylamine was added dropwise under ice-cooling, and the mixture was allowed to react at room temperature for 1 hour under pressure. After adding 50% of water to the reaction product mixture, the mixture was separated, and the organic solvent layer was concentrated under reduced pressure. 29.8 mmol of triethylamine and 50 mmol of benzene were added to the residue, and the mixture was reacted under reflux for 1 hour. After cooling the reaction product mixture, it was filtered to obtain 3.69 kg of crystals of 5-(benzoyl)ethoxycarbonylmethylene-3-allylhydanthin. These crystals were recrystallized from benzene to produce pale yellow needle crystals with a melting point of 176-178°C.
I got 7 nights. The elemental analysis values are shown below. C Day N Analyzed value 62.09 4.91 8.47 Calculated value 62.19 4.91 8.53 (C,7
Example 21 Amino-2-benzoyl-1-ethoxycarbonyl-2-isopropoxycarbonylethylene (melting point 106
00) To Z of ethylene chloride 60 containing 15.2 mmol and 35.9 mmol of pyridine, phosgene 1
Twenty minutes of ethylene chloride containing 8.3 mmol was added dropwise to the mixture, and the mixture was allowed to react at room temperature for 2 hours. To the reaction mixture was added dropwise 20% of ethylene chloride containing 15.2 mmol of benzylamine under ice cooling, and the mixture was allowed to react under a pestle at room temperature for 1 hour. After adding 50 parts of water to the reaction mixture, the organic solvent layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. 15.0 mmol of triethylamine and 200 mmol of benzene were added to Isotou, and the mixture was reacted under reflux for 1 hour. The reaction product mixture was concentrated under reduced pressure, 150M of isopropyl ether was added to the pale yellow crystals of the remaining bamboo, and then filtered to give 5-(benzo,yl)isopropoxycarbonylmethylene-3-benzyl. 3.95 crystals of hydantoin were obtained. This is recrystallized from benzene and has a melting point of 189 to 19,000.
1.94 colorless needle crystals were obtained. The elemental analysis values are shown below. C Day N Analysis value 67.61 5.16 7.19 Calculation value 6
7.34 5.14 7.14 (C22nd 2N20
Example 22 To 70' of ethylene chloride containing 26.5 mmol of 1-amino-2-benzoyl-1-ethoxycarbonyl-2-isopropoxycarbonylethylene and 79.6 mmol of pyridine was added 31.8 mmol of phosgene under ice cooling. 20% of ethylene chloride was added dropwise to the mixture, and the mixture was allowed to react at room temperature for 2 hours under pressure. Add p-anisidine hydrochloride 2 to the reaction mixture under ice cooling.
6.6 mmol was added, and the reaction was allowed to proceed at room temperature for 10 hours under ocean conditions. After adding 50 ml of water to the reaction product mixture, the layers were separated, and the organic solvent layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. 26.5 mmol of triethylamine and 150 mmol of benzene were added to the residue, and the mixture was reacted under reflux for 1.5 hours. The reaction product mixture was concentrated under reduced pressure, 150 g of isopropyl ether was added to the sticky brown crystals of Zanwan, and then filtered to give 5-(benzo,yl)isopropoxycarponylmethylene-3. 4.80 crystals of -(4-methoxyphenyl)hydantoin were obtained. This was recrystallized from inpropyl alcohol to obtain colorless acicular crystals with a melting point of 228-230°C. The elemental analysis values are shown below. C
Day N Analysis value 64.55 4.86 6.66 Calculated value 64.70 4.94 6.86 (C22 day 2
Example 23 1-Amino-2-cyano 1,2-Diethoxycarponylethylene To 60 mmol of methylene chloride containing 40.0 mmol of pyridine and 95.8 mmol of pyridine, 48.4 mmol of phosgene was added under ice cooling. Ten methane chloride containing 10 chickens were added dropwise to the mixture, and the mixture was allowed to react at room temperature for 4 hours under the rope. Add 47% of isopropylamine to the reaction mixture under ice cooling.
30 μm of methylene chloride containing 9 mmol was added dropwise to the flask and allowed to react at room temperature for 1 hour. 10 parts water to the reaction product mixture
The organic solvent layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Add 100 units of n-hexane to the residual liquid and filter it to obtain 1 crystal.
0.309 was obtained. 100 units of benzene and 33.8 mmol of triethylamine were added to the crystals, and 2
Allowed time to react. The reaction product mixture was concentrated under reduced pressure to obtain 8.70 g of crystals of 5-(cyano)ethoxycarbonylmethylene-3-isopropylhydanthin. This was recrystallized from ethanol, with a melting point of 210-211℃.
3.32 days of pale yellow needle crystals were obtained. The elemental analysis values are shown below. C Day N Analyzed value 52.21 5.19 16.61 Calculated value 52.59 5.22 16.72 (C,.day,
Example 24 35.7 mmol of phosgene was added to 60 mmol of methylene chloride containing 30.0 mmol of 1-amino-2-cyano-1,2-diethoxycarbonylethylene and 72.1 mmol of pyridine under ice cooling. Drop 10 parts of methylene chloride containing
The mixture was allowed to react for 5 hours at room temperature under a terrace. To the reaction mixture was added dropwise 30% of methylene chloride containing 30.1 mmol of allylamine under ice-cooling, and the mixture was reacted for 1 time at room temperature under a rope strainer. After adding 100 parts of water to the reaction product mixture, the layers were separated, and the organic solvent layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain a brown colored result.7.
I got 63 nights. Add 50% of isopropyl ether to this, filter it, and
-(Shea/)ethoxycarbonylmethylene-3-allylhydantoin crystals of 3.90 kg were obtained. The crystals were recrystallized from ethanol to give 2.62 kg of colorless needle crystals with a melting point of 168-16,900. The elemental analysis values are shown below. C Day N Analyzed value 53.64 4.29 17.18 Calculated value 53.01 4.45 16.86 (C,.day.,
N304) Example 25 1-amino-2-cyano-1-ethoxycarbonyl-2
- 60 mmol of methylene chloride containing 20.0 mmol of methoxycarbonylethylene and 48.0 mmol of pyridine
10' of methylene chloride containing 25.7 mmol of phosgene was added dropwise to the solution under ice-cooling, and the solution was stirred at room temperature under condensation. Immediately. It was allowed to react for a while. 24. Add isopropylamine under ice to the reaction mixture.
30 mmol of methylene chloride containing 0 mmol was added dropwise to the mixture, and the mixture was allowed to react at room temperature for 1 hour. After adding 100 parts of water to the reaction product mixture, the layers were separated, and the organic solvent layer was dried by adding anhydrous sodium sulfate, and then concentrated under reduced pressure. 100% of n-hexane was added to the residue and filtered. 15.9 mmol of triethylamine and 100 mmol of benzene were added to the separated crystals, and the mixture was reacted under reflux for 3 hours. The reaction product mixture was concentrated under reduced pressure to give 5-(cyano)
4.04 crystals of methoxycarbonylmethylene-3-isopropylhydanthin were obtained. This was recrystallized from ethanol and had a melting point of 217-218.
1.12 pale yellow needle-like crystals of 500% were obtained. The elemental analysis values are shown below. C Day N Analyzed value 50.78 4.71 17.55 Calculated value 50.63 4.67 17.72 (C, Rainbow, .
Example 26 50% of ethylene chloride containing 28.5 mmol of 1-amino-2,2-dimethoxycarbonyl-1-ethoxycarbonylethylene and 68.4 mmol of pyridine was added under ice-cooling to trichloromethyl chloroformate. Ethylene chloride (20M) containing 15.3 mmol was added dropwise to the mixture, and the mixture was reacted for 2 hours at room temperature under a vacuum cleaner. To the reaction mixture was added dropwise 30 mg of ethylene chloride containing 28.5 mmol of p-anisidine under ice-cooling.
The reaction was allowed to take place at room temperature for 2 feeding hours. After adding 50 parts of water to the reaction product mixture, the liquid was separated.
The organic solvent layer was dried over anhydrous sodium sulfate and then concentrated. Add 20 ml of methanol to the residue, then filter through a furnace,
2.55 crystals of 5-di(methoxycarbonyl)methylene-3-(p-methoxyphenyl)hydanthin were obtained. This was recrystallized from ethyl acetate, with a melting point of 204-206
1.35 pale yellow needle-shaped crystals of 0.00 were obtained. The elemental analysis values are shown below. C day N analysis value 53.61 4
．． 21 8.28 Calculated value 53.90 4.22
8.38 (C, 5 days, as 4N207) Example 27 20.0 mmol of 1-amino-2-bensoyl-1,2-diethoxycarbonylethylene and 48.0 mmol of pyridine.
To 50 mmol of methylene chloride containing 0 mmol, 20 mmol of methylene chloride containing 12.0 mmol of chloroformic acid trichloromethyl ester was added dropwise under ice-cooling, and the mixture was allowed to react at room temperature for 2 hours under a vacuum. 20 mmol of methylene chloride containing 28.0 mmol of 315-dichloroaniline was added dropwise under ice and allowed to react under a fly pestle at room temperature for 2 hours. The reaction mixture was treated as in Example 8. do,
Colorless needle crystals (melting point: 251°C) of 5-(benzoyl)ethoxycarbonylmethylene-3-(3,5-dichlorophenyl)hydanthin (melting point: 251°C) were obtained for 1.70 min. The elemental analysis values are shown below. C day N CI analysis value 55.47 3.31 6.38 16
．． 09 calculated value 55.45 3.26 6.47
16.37 (as C2, 4CI2N205) Example 28 9.4 mmol of 1-amino-2-penzoyl-1,2-diethoxycarbonylethylene and 22.5 mmol of pyridine
To 25 mmol of ethylene chloride containing 25 mmol, 10 mmol of ethylene chloride containing 6.1 mmol of chloroformic acid trichloromethyl ester was added dropwise under ice cooling, and the mixture was reacted for 2 hours at room temperature under the presence of oak. 2-methoxy-4-nito was added to the reaction mixture under ice cooling. 35' of ethylene chloride containing 13.1 mmol of aniline
was added and allowed to react under a frame at room temperature for 20 hours. Thirty percent of water was added to the resulting reaction product mixture, and then filtered. The furnace solution was separated, and the organic solvent layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. After adding 30 cores of isopropyl alcohol to the remaining sticky crystals, it was filtered to give 5-(
Benzoyl)ethoxycarbonylmethylene-3-(2
-Methoxy-4-nitrophenyl)hydantoin crystals of 1.95 kg were obtained. The crystals were recrystallized with ethanol to obtain 1.05 mm of colorless needle-like crystals with a melting point of 210-21,200. The elemental analysis values are shown below. C Day N Analyzed value 57.48 3.97 9.45 Calculated value 57
．． 41 3.90 9.56 (C2, Sun, 7N3
08) Example 29 1-amino-2-cyano-1-ethoxycarbonyl-2
30 ethylene chloride containing 10.1 mmol of methoxycarbonylethylene and 24.3 mmol of pyridine were placed under ice on a tabletop with 5.0 mmol of trichloromethyl chloroformate.
Ethylene chloride (20M) containing 4 mmol was added dropwise to the mixture, and the mixture was allowed to react at room temperature for 2 hours under reduced pressure. The reaction product mixture was added with 50 ml of ethylene chloride containing 10.1 mmol of 2-methoxy-4 nitroaniline under ice-cooling.
was added dropwise, and the mixture was reacted for 24 hours at room temperature under a maple pestle. To the reaction product mixture was added 5 tablespoons of water and then filtered to give 5-
(cyano)methoxycarbonylmethylene-3-(2-methoxy-4-nitrophenyl)hydantoin crystals, 1
．． I got 20 evenings. The furnace solution was separated, and the organic solvent layer was dried over anhydrous sodium sulfate and then concentrated. Recrystallize the residue with methanol,
5-(cyano)methoxycarbonylmethylene-3-(2
-Methoxy-4-nitrophenyl)hydantoin in pale yellow needle crystals (melting point: 248 to 250 degrees Celsius) was obtained. The elemental analysis values are shown below. C Day N Analyzed value 48.37 3.03 15.88 Calculated value 48.56 2.91 16.18 (C.4 days,
407) Example 31 50 mmol of ethylene chloride containing 20.0 mmol of 1-amino-11212-triethoxycarbonylethylene and 48.0 mmol of pyridine was cooled on ice, containing 10.8 mmol of trichloromethyl chloroformate. Ethylene chloride (20M) was added dropwise, and the mixture was reacted for 2 hours at room temperature under a female punch. To the reaction mixture was added dropwise 30' of ethylene chloride containing 20.0 mmol of benzylamine under ice-cooling, and the mixture was cooled under ice.
The reaction was allowed to take place at room temperature for two specific periods. The reaction product mixture was treated as in Example 14 to obtain colorless needle-like crystals of 5-di(ethoxycarbonyl)methylene-3-penzylhittertin (high point 149-15).
1°C) 2.15 pm was obtained. The elemental analysis values are shown below. C Day N Analyzed value 58.85 5.15 7.92 Calculated value 5
8.95 5.24 8.09 (C, 7 days.8N
206) Example 30 To 25 units of ethylene chloride containing 10.0 mmol of 1-amino-1,2,2-triethoxycarbonylethylene and 24.9 mmol of pyridine, 6.7 g of trichloromethyl chloroformate was added under ice. 15 mmol of ethylene chloride was added dropwise to the mixture, and the mixture was allowed to react at room temperature for 2 hours under the open ocean. Add cyclohexylamine 16 to the reaction mixture under ice.
．． 10% of ethylene chloride containing 9 mmol was added dropwise, and the reaction was carried out in one batch at room temperature under condensation. The reaction product mixture was treated as in Example 14 to obtain refractory needle crystals of 5-di(ethoxycarbonyl)methylene-3-cyclohexylhydanthin (melting point 118-12000) 1.08
I got the evening. The elemental analysis values are shown below. C Day N Analysis value 56.92 6.42 8.31 Calculated value
56.79 6.55 8.28 (C, 6th 22N
206) Example 32 Trichloromethylester chloroformate 12 was added to 50' of ethylene chloride containing 20.0 mmol of 1-amino-1,2,2-trimethoxycarbonylethylene and 48.0 mmol of pyridine under ice cooling. Twenty minutes of ethylene chloride containing 0.3 mmol was added dropwise to the mixture, and the mixture was reacted for 2 hours at room temperature under a vacuum cleaner. To the reaction mixture was added dropwise 30 mmol of ethylene chloride containing 20.0 mmol of 2,5-dichloroaniline under ice cooling, and the reaction mixture was allowed to react at room temperature for 24 hours under reduced pressure. The reaction product mixture was treated as in Example 14 to obtain "5-di(ethoxycarbonyl)methylene-3-(21
Colorless needle crystals of 5-dichlorophenyl)hydantoin (
A temperature of 3.59 degrees Celsius (178-179° C.) was obtained. The elemental analysis values are shown below. C day N CI

Claims (1)

[Claims] 1 Formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 and R^2 each have a carbon number of 1 to
4 represents an alkyl group, and X represents an alkoxycarbonyl group having 2 to 5 carbon atoms, a benzoyl group, or a cyano group. ) is reacted with phosgene or chloroformic acid trichloromethyl ester represented by the formula R^3NH_2 [wherein R ^3 is a hydrogen atom, an alkyl group with 1 to 7 carbon atoms, an alkenyl group with 3 to 7 carbon atoms, a cycloalkyl group with 5 to 7 carbon atoms, a benzyl group, ▲numerical formula, chemical formula, table, etc.▼ (in the formula , R^4 represents an alkyl group having 1 to 7 carbon atoms, an alkoxyl group having 1 to 4 carbon atoms, a halogen atom, or a nitro group, and n is 0, 1, 2 or 3. show. ] Formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^2, R^3 and X each have the same meaning as above. ) A method for producing 5-(alkoxycarbonyl)methylenehydantoin.