KR810000003B1 - Process for the preparing 1-thiadiazolyl-6-acyloxytetrahydropyrimidinones - Google Patents

Abstract

1-Thiadiazolyl-6-acyloxytetrahydropyrimidinones (I; R1 = alkyl, alkenyl, haloalkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl or cycloalkyl; R2 = alkyl, alkenyl, haloalkyl; R6 = alkyl, haloalkyl, alkenyl, alkinyl, alkoxyalkyl, cycloalkyl; X = alkyl, halogen, haloalkyl, nitro, cyano, alkoxy; m, n = O-3; R7, R8 = methyl, ethyl), useful as herbicide, were prepd. by reaction of compd. (II) and acid anhydride (III) in the presence of toluene sulfonic acid at 50-90≰C. The reaction of compd. (II) and (IV) at 10-30≰C also give title compound.

Description

Method for preparing 1-thiadiazolyl-6-acyloxy tetrahydro pyrimidinone

The present invention relates to a method for preparing a new compound represented by formula (I).

(여기서 R⁴및 R⁵는 각각 수소 또는 알킬이다)이며 R³은 수소 또는

이고 R⁶는 알킬, 할로알킬, 알케닐, 알키닐, 알콕시알킬, 싸이클로알킬 또는

(여기서 X는 알킬, 수소, 할로알킬, 니트로, 씨아노 또는 알콕시, m과 n은 각각 0-3의 정수이다)이다.Wherein R ¹ is alkyl, alkenyl, haloalkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl or cycloalkyl, R ² is alkyl, alkenyl, haloalkyl or

Wherein R ⁴ and R ⁵ are each hydrogen or alkyl, and R ³ is hydrogen or

And R ⁶ is alkyl, haloalkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl or

Wherein X is alkyl, hydrogen, haloalkyl, nitro, cyano or alkoxy, m and n are each an integer of 0-3.

(여기서 R⁴및 R⁵는 각각 수소 또는 저급알킬이다)이고 R³은 수소 또는

이며 R⁶은 저급알킬, 저급클로로알킬, 저급브로모알킬, 저급알키닐, 저급알톡시알킬, 탄소원자 3-7의 싸이클로알킬 또는 -(CH₂)m

(여기서 X는 저급알킬, 저급알콕시, 수소 또는 저급할로알킬이고 m과 n은 각각 0-3의 정수이다)을 나타낸다. 여기에서 사용되는 ＂저급＂이란 탄소원자 6까지의 직쇄 또 측쇄 탄소결합을 의미한다.In more detail the present invention, R ¹ is lower alkyl, lower alkenyl, lower chloroalkyl, lower bromoalkyl, trifluoromethyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylsulfinyl or carbon Cycloalkyl of atoms 3-7, R ² is lower alkyl, lower alkenyl, lower cycloalkyl, lower bromoalkyl or

Wherein R ⁴ and R ⁵ are each hydrogen or lower alkyl and R ³ is hydrogen or

And R ⁶ is lower alkyl, lower chloroalkyl, lower bromoalkyl, lower alkynyl, lower alkoxyalkyl, cycloalkyl of 3-7 carbon atoms or-(CH ₂ ) m

Wherein X is lower alkyl, lower alkoxy, hydrogen or lower haloalkyl and m and n are each an integer of 0-3. As used herein, "lower" means a straight or branched carbon bond of up to 6 carbon atoms.

이고 R⁶가 전술한 바와같은 본 발명의 화합물은 R³이 수소인 일반식(II)로 표시되는 상응하는 본 발명의 화합물을 톨루엔 술론산의 촉매량존재하에서 일반식(III)으로 표시되는 산무수물로 반응시켜서 제조된다.The compounds of the present invention are useful as preparations as expected. R ³ is

And R ⁶ is a compound of the present invention wherein the compound of the present invention represented by formula (II) wherein R ³ is hydrogen is an acid anhydride represented by formula (III) in the presence of a catalytic amount of toluene sulfonic acid. It is prepared by reacting with.

Wherein R ¹ and R ² are as described above.

In the above formula, R ⁶ is as described above.

시간동안 교반하면서 가열하는 것이 효과적이고 반응혼합물 냉각시켜 원하는 생성물이 침전되면 여과에 의하여 회수하고 또는 그속에 용해되었다면 유기반응매질을 증발시켜서 회수할 수 있다.This reaction combines the reactants and the catalyst at room temperature in the presence of an inert organic reaction medium and then the reaction mixture is brought to a temperature of 50-90 ° C. in a steam bath.

Heating with stirring over time is effective and the reaction mixture can be cooled and recovered by filtration if the desired product precipitates or by evaporation of the organic reaction medium if dissolved therein.

In some cases, an acid anhydride can be used as a solvent of the general formula (R) compound without using an inert solvent as the reaction medium. When using lower alkanone anhydride, water can be added to the reaction mixture to precipitate the desired product after completion of the reaction. The product is purified by conventional methods such as recrystallization.

인 본 발명의 화합물은 3급 아민과 같은 산수용체의 존재하에 일반식(II)로 표시되는화합물을 일반식(IV)로 표시되는 산할라이드와 반응시켜 제조할 수 있다.R ³ is

The compound of the present invention may be prepared by reacting a compound represented by the general formula (II) with an acid halide represented by the general formula (IV) in the presence of an acid acceptor such as a tertiary amine.

In the above formula, R ⁶ is as described above.

This preparation method can be used when the desired anhydride of formula (III) cannot be used. This reaction is slowly added while stirring the acid chloride of formula (IV) to a solution of the compound represented by formula (II) in an equimolar amount dissolved in an inert organic solvent at a temperature of about 10-30 ° C. in the presence of an acid acceptor. It is effective. After the addition is complete, the reaction mixture is heated to a degree up to the reflux temperature of the mixture to ensure that the reaction is complete. After that, if the desired product is dissolved in it, the reaction mixture can be filtered first to remove the acid acceptor chloride and the solvent is removed or, if precipitated, filtered, washed and purified. Compounds of the invention wherein R ³ is hydrogen are prepared by heating the compound represented by formula (V) in an aqueous acidic reaction medium diluted for about 10-60 minutes.

Wherein R ¹ and R ² are as described above and R ⁷ and R ⁸ are methyl or ethyl. The temperature is used from 70 ° C. up to the reflux temperature of the reaction mixture. The reaction medium consists of an aqueous solution of dilute inorganic acid, such as hydrochloric acid at a concentration of about 0.5-5%. After completion of the reaction, the product can be recovered as a precipitate by cooling the reaction mixture, which can be further purified or used by conventional methods such as recrystallization. The compound represented by general formula (IV) can be prepared by reacting 1 molar amount of the isocyanate dimer of general formula (VI) with about 2 moles of acetal represented by general formula (VII).

Wherein R ¹ is as described above.

Wherein R ² , R ⁷ and R ⁸ are as described above.

This reaction can be carried out by heating the isocyanate dimer and acetal mixture in an inert organic reaction medium such as benzene at the reflux temperature of the reaction mixture. Heating at reflux is continued for about 2-30 minutes to complete the reaction and then the desired product can be recovered by evaporation of the reaction medium and can be further purified or used by conventional techniques.

The isocyanate dimer of general formula (VI) can be prepared by reacting thiadiazole represented by general formula (VII) with phosgene.

Wherein R ¹ is as described above. This reaction is effective to add a slurry or solution of thiadiazole in a suitable organic solvent such as ethyl acetate to a phosgene solution saturated in an organic solvent such as ethyl acetate. The resulting mixture is stirred at room temperature for 4-24 hours. Nitrogen gas is blown into the reaction mixture to remove unreacted phosgene. The desired product is recovered by filtration if something like precipitation is produced or by evaporation of the organic solvent used if dissolved in it. This product can be used as is or further purified if desired.

Examples of the thiadiazoles represented by the general formula (VIII) useful for preparing the compounds of the present invention include 5-methyl-2-amino-1,3,4-thiadiazole, -5-ethyl-2-amino- 1,3,4-thiadiazole, 5-propyl-2-amino-1,3,4-thiadiazole, 5-acetyl-2-amino-1,3,4-thiadiazole, 5-chloro Methyl-2-amino-1,3,4-thiadiazole, 5-β chloroethyl-2-amino-1,3,4-thiadiazole, -2-γ-chromopropyl-2-amino- 1,3,4-thiadiazole, 5-trichloromethyl-2-amino-1,3,4-thiadiazole, 5-methoxy-2-amino-1,3,4-thiadiazole, 5-ethoxy-2-amino-1,3,4-thiadiazole, 5-propoxy-2-amino-1,3,4-thiadiazole, 5-butyloxy-2-amino-1,3 , 4-thiadiazole, 5-hexyloxy-2-amino-1,3,4-thiadiazole, 5-methylthio-2-amino-1,3,4-thiadiazole, 5-ethylthio 2-amino-1,3,4-thiadiazole, 5-propylthio-2-amino-1,3,4-thiadiazole, 5-butylthio-2-amino-1,3,4-thia Diazole, 5-methylsulfonyl-2-amino-1 , 3,4-thiadiazole, 5-ethylsulfonyl-2-amino-1,3,4-thiadiazole, 5-butylsulfonyl-2-amino-1,3,4-thiadiazole, 5 -Methylsulfinyl-2-amino-1,3,4-thiadiazole, 5-ethylsulfonyl-2-amino-1,3,4-thiadiazole, 5-propylsulfinyl-2-amino-1 , 3,4-thiadiazole, 5-t-butyl-2-amino-1,3,4-thiadiazole, 5-trifluoromethyl-2-amino-1,3,4-thiadiazole, 5-cyclopropyl-2-amino-1,3,4-thiadiazole, 5-cyclobutyl-2-amino-1,3,4-thiadiazole, 5-cyclopentyl-2-amino- 1,3,4-thiadiazole, 5-cyclohexyl-2-amino-1,3,4-thiadiazole, 5-cycloheptyl-2-amino-1,3,4-thiadiazole, And the like.

When the acetal represented by formula (VII) is not readily available, the amine represented by formula (IX) can be prepared by reacting with dimethyl acetal or diethyl acetal of β-bromopropion aldehyde.

In the above formula, R ² is as described above.

This reaction can be carried out by mixing 1-2 molar amounts of the amine represented by the general formula (IX) with 1 molar amount of acetal of β-bromo propionaldehyde in an equimolar ratio dissolved in an inert organic reaction medium such as methanol. The reaction mixture is heated at reflux for 4-8 hours, then cooled to room temperature and neutralized by adding sufficient alkali metal hydroxide or carbonate to complete the reaction by stirring at room temperature for 24 hours to complete the reaction and filtration of the reaction mixture. The filtrate is then distilled off under reduced pressure to yield the desired product.

-부틸아민,

-부틸아민, 펜틸아민, 헥실아민, 아릴아민, 프로파길아민, 2-부텐일아민, 3-부텐일아민, 3-펜텐일아민, 4-펜텐일아민, 5-헥실일아민, 1-메틸-2-프로피닐아민, 1,1,-디메틸-2-프로피닐아민, 1-에틸-2-프로피닐아민, 1,1-디에틸-2-프로피닐아민, 1-프로피닐-2-프로피닐아민, 1,1-디프로필-2-프로피닐아민, 1-코로로아릴아민, 1-브로모아릴아민, 4-크로로-2-부텐일아민, 6-크로로-4-헥센일아민 등이 있다.Examples of the compound represented by the general formula (IX) include methyl adine, ethylamine, propylamine, isopropylamine,

Butylamine,

Butylamine, pentylamine, hexylamine, arylamine, propargylamine, 2-butenylamine, 3-butenylamine, 3-pentenylamine, 4-pentenylamine, 5-hexylylamine, 1-methyl -2-propynylamine, 1,1, -dimethyl-2-propynylamine, 1-ethyl-2-propynylamine, 1,1-diethyl-2-propynylamine, 1-propynyl-2- Propynylamine, 1,1-dipropyl-2-propynylamine, 1-corroarylamine, 1-bromoarylamine, 4-chloro-2-butenylamine, 6-chloro-4-hex Selenamine.

Examples of suitable acid anhydrides represented by general formula (III) include acetic anhydride, propionic anhydride, pentane anhydride, hexane anhydride, acrylic anhydride, butene anhydride, pentene anhydride, chloride acetate anhydride, bromoacetic anhydride, β-crobutane anhydride , Cyclohexyl carboxy anhydride, benzoic anhydride, toruic anhydride, 4-chlorobenzoic anhydride, 3-bromobenzoic anhydride, 4-fluorobenzoic anhydride, 4-methoxybenzoic anhydride, 4-ethoxybenzo Ik anhydride, 4-chloromethylbenzoic anhydride, 4-trifluoromethylbenzoic anhydride, 3,4,5-trichlorobenzoic anhydride, phenyl acetic anhydride, 4-methylphenic acetal anhydride, β-phenylpropion Anhydride, γ-phenylbutane anhydride, propinoic anhydride, butinoic anhydride, methoxy acetic anhydride, β-methoxy propion anhydride, γ-ethoxy butanoic anhydride, and the like.

Examples of suitable acid chlorides represented by general formula (IV) useful for preparing the compounds of the present invention are acid chlorides of the same acid as described above in the examples of acid anhydrides.

The preparation method of the compound of the present invention is further described according to the following examples.

Example 1

Preparation of 5-methyl-1,3,4-thiadiazol-2-yl isocyanate dimer

Saturated solution of phosgene dissolved in 100 ml of ethyl acetate is placed in a glass reaction vessel equipped with a mechanical stirrer. 40 g of a slurry of 5-methyl-2-amino-1,3,4-thiadiazole dissolved in 300 ml of ethyl acetate is added to the reaction vessel, and the resulting mixture is stirred for 16 hours to form a precipitate. The reaction mixture was washed with nitrogen gas to remove unreacted phosgene, the washed mixture was filtered to recover the precipitate, and the precipitate was recrystallized to give the desired product 5-methyl-1,3,4-thiadiazol-2-yl isocyanate equivalent. Sieve is generated.

Example 2

Preparation of Dimethyl Acetal of 3-Methylamino Propion Aldehyde

1.0 mole of methylamine, 0.5 mole of dimethyl acetal of tromoprion aldehyde and 100 ml of methanol are placed in a glass reactor equipped with a mechanical stirrer, thermometer and reflux cooler. The reaction mixture is heated with stirring at reflux for 4 hours. After this time the reaction mixture is cooled to room temperature and NaOH20g is added. The reaction mixture is further stirred for 8 hours. The reaction mixture is filtered and the filtrate is distilled under reduced pressure to give dimethyl acetal of the desired product 3-methylamino propion aldehyde.

Example 3

Preparation of Digityl Acetal of 3-1-methyl-3- (5-methyl-1,3,4-thiadiazol-2-yl) ureido propionaldehyde

A mixture of 0.05 mole of 5-methyl-1,3,4-thiadiazol-2-yl isocyanate dimer and 0.1 mole of dimethyl acetal of 3-methyl amino propionaldehyde and 60 ml of benzene was prepared in a glass reactor equipped with a mechanical stirrer and a reflux cooler. Put it in. The reaction mixture is heated to reflux for 15 minutes. After this time the mixture removes benzene under reduced pressure to give a solid product as a residue. Recrystallization of this residue yields dimethyl acetal of the desired product 3-1-methyl-3- (5-methyl-1,3,4-thiadiazol-2-yl) ureido propionaldehyde.

Example 4

Preparation of Tetrahydro-1- (5-methyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone

3- [1-methyl-3- (5-methyl-1,3,4-thiadiazol-2-yl) ureido] 15 g of dimethyl acetal of propionaldehyde, 400 ml of water and 4 ml of hydrochloric acid were refluxed with a mechanical stirrer, thermometer and Place in a glass reactor equipped with a cooler. The reaction mixture is heated at reflux for 15 minutes. The reaction mixture is filtered hot and the filtrate is considered to form a precipitate. The precipitate is recovered by filtration, dried and recrystallized to give the desired product Tedra Hydro-1- (5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2 -(1H) -pithymidion is produced.

Example 5

Preparation of Tetrahydro-1- (5-methyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-acetyloxy-2 (1H) -pyrimidinone

0.1 mol of tetrahydro-1- (5-methyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone, 0.11 mol of acetic anhydride, 0.05 g of toluene sulfoic acid and 100 ml of benzene are placed in a glass reaction vessel equipped with a mechanical stirrer and a thermometer. The reaction mixture is heated with steam stirring for 2 hours. After this time, the reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure, leaving a residue. Recrystallization of the residue gave the desired product tetra hydro-1- (5-methyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-acetyloxy-2 (1H) -pyrimidinone. do.

Example 6

Preparation of 5-methoxy-1,3,4-thiadiazol-2-yl isocyanate dimer

100 ml of saturated solution of phosgene dissolved in ethyl acetate is placed in a glass reactor equipped with a mechanical stirrer. 40 g of a slurry of 5-methoxy-2-amino-1,3,4-thiadiazole dissolved in 300 ml of ethyl acetate is added to the reaction vessel, and the resulting mixture is stirred for 16 hours to form a precipitate. Washing the reaction mixture with nitrogen gas removes unreacted phosgene. Filtration of the washed mixture recovers precipitation. Recrystallization of the precipitate yields the desired product 5-methoxy-1,3,4-thiadiazol-2-yl isocyanate dimer.

Example 7

Preparation of Dimetal Acetal of 3-Methyl Amino Propion Aldehyde

2.0 mole of ethylamine, 1.0 mole of dimethyl acetal of 3-propo propionaldehyde and 100 ml of methanol are placed in a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux cooler. The reaction mixture is heated with stirring for 5 hours at reflux. After this time, the reaction mixture is cooled to room temperature and Na0H20g is added. The reaction mixture is further stirred for 12 hours. Filtration of the reaction mixture and distillation of the filtrate under reduced pressure yielded the dimetal acetal of the desired product 3-ethyl amino propion aldehyde.

Example 8

Preparation of dimethyl acetal of 3- [1- (ethyl-3- (5-methoxin-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde

0.05 mol of 5-methoxy-1,3,4-thiadiazol-2-yl isocyanate dimer, 0.1 mol of dimethyl acetal of 3-ethylamino propionaldehyde and 60 ml of benzene were placed in a glass reactor equipped with a mechanical stirrer and a reflux cooler. Put it in. The reaction mixture is heated at reflux for 15 minutes.

After this time the mixture is removed from the benzene under reduced pressure to give a solid product as a residue. Recrystallization of the residue yields digityl acetal of the desired product 3- [1- (ethyl-3- (5-methoxy-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde.

Example 9

Preparation of Tetra Hydro-1- (5-methoxy-1,3,4-thiadiazol-2--yl) -3-ethyl-6-hydroxy-2 (1H) -pyrimidinone

3- [1-ethyl-3- (5-methoxy-1,3,4-thiadiazol-2-yl) ureido] 400 ml of 15 g mol of dimethyl acetal of propionaldehyde and 4 ml of hydrochloric acid were added to a mechanical stirrer, thermometer and reflux. Place in a glass reaction vessel equipped with a cooler.

The reaction mixture is heated at reflux for 15 minutes. The reaction mixture is filtered when hot and the filtrate is cooled down to form a precipitate. The precipitate is recovered by filtration and dried to crystallize the desired product tetrahydro-1- (5-methoxy-1,3,4-thiadiazol-2-yl) -3-ethyl-6-hydroxy-2 (1H) -pyrimidinone is produced.

Example 10

Preparation of Tetrahydro-1- (5-methoxy-1,3,4-thiadiazol-2yl) -3-ethyl-propionyloxy-2 (1H) -pyrimidinone

Tetrahydro-1- (5-methoxy-1,3,4-thiadiazol-2-yl) -3-ethyl-6-hydroxy-2 (1H) -pyrimidinone 0.1 mole, propionic anhydride 0.11 mole , 0.05 g of totoene sulfoic acid and 100 ml of benzene are placed in a glass reactor equipped with a mechanical stirrer and thermometer. After cooling the reaction mixture to room temperature and removing the solvent under reduced pressure, a residue is left. Recrystallization of the residue affords the desired product tetra hydro-1- (5-methoxy-1,3,4-thiadiazol-2-yl) -3-ethyl-6-propionyloxy-2 (1H) -pyrimidinone. Is generated.

Example 11

Preparation of 5-methylthio-1,3,4-thiadiazol-2-yl isocyanate dimer

A saturated solution of posogen dissolved in 100 ml of ethyl acetate is placed in a glass reactor equipped with a mechanical stirrer.

45 g of a slurry of 5-methylthio-2-amino-1,3,4-thiadiazole dissolved in 300 ml of ethyl acetate was added to the reaction vessel, and the resulting mixture was stirred for 16 hours to form a precipitate. Washing the reaction mixture with nitrogen gas removes unreacted posogen. Filtration of the washed mixture recovers precipitation. Recrystallization of the precipitate yields the desired product 5-methylthio-1,3,4-thiadiazol-2-yl isocyanate dimer.

Example 12

Preparation of 3-propyl amino propionaldehyde dimethyl acetal

2.0 moles of propylamine, dimethyl acetal 1.0 moles of 3-propomopropion aldehyde and 100 ml of methanol are placed in a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux cooler.

The reaction mixture is heated with stirring at reflux for 3 hours. After this time, the reaction mixture is cooled to room temperature and NaOH20g is added. Filtration of the reaction mixture and distillation of the filtrate under reduced pressure yielded dimethyl acetal of the desired product 3-propyl amino propionaldehyde.

Example 13

Preparation of dimethyl acetal of 3- [1-propyl-3- (5-methylthio-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde

A mixture of 0.05 mol of 5-methylthio-1,3,4-thiadiazol-2-yl isocyanate dimer, 0.1 mol of 3-propyl amino propionaldehyde and 60 ml of benzene was placed in a glass reaction vessel equipped with a mechanical stirrer and a reflux cooler. Put it in. The reaction mixture is heated at reflux for 15 minutes. After this time the mixture removes benzene under reduced pressure to give a solid product as a residue. Recrystallization of the residue gives the dimethyl acetal of the desired product 3- [1-propyl-3- (5-methylthio-1,3,4-thiadiazol-2-yl) eureido] propion aldehyde.

Example 14

Preparation of Tetrahydro-1- (5-methylthio-1,3,4-thiadiazol-2-yl) -3-propyl-6-hydroxy-2 (1H) -pyrimidinone

3- [1-propyl-3- (5-methylthio-1,3,4-thiadinazol-2-yl) ureido] 15 g of dimethylacetal of propionaldehyde, 400 ml of water and 4 ml of hydrochloric acid were mixed with a mechanical stirrer and a thermometer. Place in a glass reaction vessel equipped with a reflux condenser. The reaction mixture is heated at reflux for 15 minutes. The reaction mixture is filtered while hot and the filtrate is cooled to precipitate. The precipitate is recovered by filtration and recrystallized to give the desired product tetra hydro-1- (5-methylthio-1,3,4-thiadiazol-2-yl) -3-propyl-6-hydroxy-2 (1H) Pyrimidinone is produced.

Example 15

Preparation of tetra hydro-1- (5-methylthio-1,3,4-thiadiazol-2-yl) -3-propyl-6-butanoyloxy-2 (1H) pyrimidinone

Tetra hydro-1- (5-methylthio-1,3,4-thiadiazol-2-yl) 3-propyl-6-hydroxy-2 (1H) -pyrimidinone 0.1 mole, butanoic anhydride 0.11 mole , 0.05 g of toluene sulfoic acid and 100 ml of benzene are placed in a glass reaction vessel equipped with a mechanical stirrer and a thermometer.

The reaction mixture is heated with stirring for 2 h in a steam bath. After this time, the reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure, leaving a residue. Recrystallization of the residue affords the desired product tetra hydro-1- (5-methylthio-1,3,4-thiadiazol-2-yl) -3-propyl-6-butanoyloxy-2 (1H) -pyrimidinone. Is generated.

Example 16

Preparation of 5-methylsulfonyl-1,3,4-thiadiazol-2-yl isocyanate dimer

Saturated solution of phosgene dissolved in 100 ml of ethyl acetate is placed in a glass reaction vessel equipped with a mechanical stirrer. 50 g of a slurry of 5-methylsulfonyl-2-amino-1,3,4-thiadiazole dissolved in 300 ml of ethyl acetate is added to the reaction vessel, and the resulting mixture is stirred for 16 hours to form a precipitate. Washing the reaction mixture with nitrogen gas removes unreacted phosgene.

Filtration of the washed mixture recovers the precipitate. Recrystallization of the precipitate yields the desired product 5-methylsulfonyl-1,3,4-thiadiazol-2-yl isocyanate dimer.

Example 17

Preparation of Dimethyl Acetal of 3-aryl Amino Propion Andide

1.0 mole of aryl amine, 0.5 mole of dimethyl acetal of 3-bromo propionaldehyde and 100 ml of methanone are placed in a glass reactor equipped with a mechanical stirrer, thermometer and reflux cooler. The reaction mixture is heated with stirring for 8 hours at reflux temperature. After this time the reaction mixture is cooled to room temperature and 20 g of NaOH is added.

The reaction mixture is stirred for another 14 hours. Filtration of the reaction mixture and distillation of the filtrate under reduced pressure yielded dimethyl acetal of the desired product 3-acetylaminopropion aldehyde.

Example 18

Preparation of dimethyl acetal of 3- (1-aryl-3- (5-methylsulfonyl-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde

0.05 roll of 5-methylsulfonyl-1,3,4-thiadiazol-2-yl isocyanate dimer, 0.1-mol of dimethylacetal and benzene of 3-arylaminopropion aldehyde and 60 ml of glass equipped with mechanical stirrer and reflux cooler Place in reaction vessel. The reaction mixture is heated for 15 minutes. After this time the mixture removes benzene under reduced pressure to give a solid product as a residue.

Recrystallization of the residue gives the dimethyl acetal of the desired product 3- [1-aryl-3- (5-methylsulfonyl-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde.

Example 19

Preparation of Tetra Hydro-1- (5-methylsulfonyl-1,3,4-thiadiazol-2-yl) -3-aryl-6-hydroxy-2 (1H) -pyramimidone

15 g of dimethyl acetal of 3-1-methyl-3- (5-methylsulfonyl-1,3,4-thiadiazol-2-yl) ureido propionaldehyde, 400 ml of water and 4 ml of hydrochloric acid were added to a mechanical stirrer, thermometer and reflux. Place in a glass reaction vessel equipped with a cooler. The reaction mixture is heated at reflux for 15 minutes. The reaction mixture is filtered when hot and the filtrate is cooled to precipitate. The precipitate is recovered by filtration, dried and recrystallized to give the desired product tetra hydro-1- (5-methyl sulfonyl-1,3,4-thiadiazol-2-yl) -3-aryl-6-hydroxy-2 (1H) -pyrimidinone is produced.

Example 20

Preparation of Tetra Hydro 1- (5-methylsulfonyl-1,3,4-thiadiazol-2-yl) -3-aryl-6-cyclohexyl carbonyloxy-2 (1H) -pyrimidinone

Tetrahydro-1- (5-methylsulfonyl-1,3,4-thiadiazol-2-yl) -3-aryl-6-hydroxy-2 (1H) -pyrimidinone 0.1 mole, cyclohexane carboxylic acid 0.11 mol of anhydride, 0.05 g of toluenesulfonic acid and 100 ml of benzene are placed in a glass reactor equipped with a mechanical stirrer and thermometer. The reaction mixture is heated with stirring for 2 h in a steam bath. After this time, the reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure, leaving a residue.

Recrystallization of the residue affords the desired product tetra hydro-1- (5-methylsulfonyl-1,3,4-thiadiazol-2-yl) -3-aryl-6-cyclohexyl carbonyloxy-2 (IH)- Pyrimidinone is produced.

Example 21

Preparation of 5-cyclopropyl-1,3,4-thiadiazol-2-yl isocyanate dimer

Saturated solution of phosgene dissolved in 100 ml of ethyl acetate is placed in a glass reaction vessel equipped with a mechanical stirrer. 50 g of a slurry of 5-cyclopropyl-2-amino-1,3,4-thiadiazole dissolved in 300 ml of ethyl acetate is added to the reaction vessel, and the resulting mixture is stirred for 16 hours to form a precipitate.

Washing the reaction mixture with nitrogen gas removes unreacted phosgene. The precipitate which filtered the washed mixture is recovered. The desired product 5-cyclopropyl-1,3,4-thiadiazol-2-yl isocyanate dimer is produced which recrystallizes the precipitate.

Example 22

Preparation of dimethyl acetal of 3-propargyl amino propion aldehyde.

2.0 moles of propargyl amine, 1.0 mole of dimethyl acetal of 3-bromo propion aldehyde and 100 ml of methanol are placed in a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux cooler.

The reaction mixture is heated with stirring at reflux for 6 hours. After this time the reaction mixture is cooled to room temperature and NaOH20g is added. The reaction mixture is further stirred for 18 hours. Filtration of the reaction mixture and distillation of the filtrate under reduced pressure yielded dimethyl acetal of the desired product 3-propargyl amino propion aldehyde.

Example 23

Preparation of dimethyl acetal of 3- (1-propargyl-3- (5-cyclopropyl-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde

A mixture of 0.05 mol of 5-cyclopropyl-1,3,4-thiadiazol-2-yl isocyanate dimer, 0.1 mol of dimethyl acetal of 3-propargyl-amino propionaldehyde and 60 ml of benzene was refluxed with a mechanical stirrer. Place in a glass reactor equipped with a cooler.

The reaction mixture is heated at reflux for 15 minutes. After this time the mixture is removed from the benzene under reduced pressure to give a solid product as a residue. Recrystallization of the residue gives the dimethyl acetal of the desired product 3- [1-propargyl-3- (5-cyclopropyl-1,3,4-thiadiazol-2-yl) ureido propionaldehyde.

Example 24

Preparation of Tetra Hydro-1- (5-cyclopropyl-1,3,4-thiadiazol-2-yl) -3-propargyl-6-hydroxy-2 (1H) -pyrimidinone

3- [1-propargyl-3- (5-cyclopropyl-1,3,4-thiadiazol-2-yl) ureido] 15 g of dimethyl acetal of propionaldehyde, 400 ml of water and 4 ml of hydrochloric acid were added to a mechanical stirrer, Place in a glass reaction vessel equipped with a thermometer and reflux condenser. The reaction mixture is heated at reflux for 15 minutes. The reaction mixture is filtered when hot and the filtrate is cooled to form a precipitate. The precipitate is recovered by filtration, dried and recrystallized to give the desired product tetra hydro-1- (5-cyclopropyl-1,3,4-thiadiazol-2-yl) -3-propargyl-6-hydroxy- 2 (1H) -pyrimidinone is produced.

Example 25

Preparation of Tetrahydro-1- (5-cyclopropyl-1,3,4-thiadiazol-2-yl) -3-propargyl-6-benzoyloxy-2 (1H) -pyrimion

Tetrahydro-1- (5-cyclopropyl-1,3,4-thiadiazol-2-yl) -3-propargyl-6-hydroxy-2 (1H) -pyrimidinone 0.1 mole, of benzo 0.11 mol of acid anhydride, 0.05 g of toluene sulfoic acid and 100 ml of benzene are placed in a glass reaction vessel equipped with a mechanical stirrer and thermometer. The reaction mixture is heated with stirring for 2 h in a steam bath. After this time, the reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure, leaving a residue. Recrystallization of the residue affords the desired product tetra hydro-1- (5-cyclopropyl-1,3,4-thiadiazol-2-yl) -3-propargyl-6-benzoicoxy-2 (1H) -pyri. Midinone is produced.

Example 26

Preparation of 5-triflomethyl-1,3,4-thiadiazol-2-yl isocyanate dimer

Saturated solution of phosgene dissolved in 100 ml of acetate is placed in a glass reaction vessel equipped with a mechanical stirrer. 45 g of a slurry of 5-trifluoromethyl-2-amino-1,3,4-thiadiazole dissolved in 300 ml of ethyl acetate was added to the reaction vessel, and the resulting mixture was stirred for 16 hours to form a precipitate. Removing the reaction mixture with nitrogen gas removes unreacted posgen.

Filtration of the washed mixture recovered 48 g of white solid. Recrystallization of this solid from dimethyl formamide yields the desired product 5-triflo methyl-1,3,4-thiadiazol-2-yl isocyanate dimer.

Example 27

Preparation of dimethyl acetal of 3- [1-methyl-3- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde

A mixture of 9.5 g of 5-trifluoromethyl-1,3,4-thiadiazol-2-yl isocyanate dimer and 5.8 g of dimethyl acetal of 3-methyl-amino propionaldehyde and 60 ml of benzene was equipped with a mechanical stirrer and a reflux cooler. Into a glass reaction vessel.

The reaction mixture is heated at reflux for 15 minutes. After this time the mixture is removed from the benzene under reduced pressure to give a solid product as a residue. Recrystallization of this product yields the dimethyl acetal of the desired product 3- [1-methyl-3-3- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde. do.

Example 28

Preparation of tetra hydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone

15 g of dimethyl acetal of 3- [1-methyl-3- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) ureido] propionaldehyde, 400 ml of water and 4 ml of hydrochloric acid were added to a mechanical stirrer, Place in a glass reaction vessel equipped with a thermometer and reflux condenser. The reaction mixture is heated at reflux for 15 minutes. The reaction mixture is filtered when hot and the filtrate is cooled to form a precipitate. The precipitate is recovered by filtration, dried and recrystallized to give the desired product tetra hydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3--methyl-6-hydroxy -2 (1H) -pyrimidinone is produced.

Example 29

Preparation of tetra hydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-acetaloxy-2 (1H) -pyrimidinone

Tetrahydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone 0.1 mol, acetic anhydride 0.11 mol, 0.05 g of toluene sulfoic acid and 100 ml of benzene are placed in a glass reaction vessel equipped with a mechanical stirrer and thermometer. The reaction mixture is heated with stirring for 2 h in a steam bath. After this time, the reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure, leaving a residue. Recrystallization of the residue affords the desired product tetra hydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-acetyloxy-2 (1H) -pyrimi Dion is produced.

Example 30

-부틸-1,3,4-티아디아졸-2-일 이소시아네이드 이량체의 제조5-

Preparation of -butyl-1,3,4-thiadiazol-2-yl isocyanide dimer

-부틸-2-아미노-1,3,4-티아디아졸의 슬러리 10g을 반응용기에 첨가하고 생성된 혼합물을 16시간동안 교반하면 침전물이 생성된다. 반응혼합물을 질소가스로 세척하면 미반응 포스겐이 제거된다.A saturated solution of phosgene dissolved in 100 ml of ethyl acetate is placed in a glass reaction vessel equipped with a mechanical stirrer. 5- dissolved in 300 ml of ethyl acetate

10 g of a slurry of -butyl-2-amino-1,3,4-thiadiazole is added to the reaction vessel and the resulting mixture is stirred for 16 hours to form a precipitate. Washing the reaction mixture with nitrogen gas removes unreacted phosgene.

-부틸-1,3,4-티아디아졸-2-일 이소시아네이트 이량체가 생성된다.The washed mixture was filtered to give the desired product as a solid having a melting point of 261-263 ° C. 5-

-Butyl-1,3,4-thiadiazol-2-yl isocyanate dimer is produced.

Example 31

-부틸-1,3,4-티아디아졸-2-일 유레이도 프로피온 알데하이드의 디메틸 아세탈의 제조3-1-methyl-3- (5-

Preparation of Dimethyl Acetal of -Butyl-1,3,4-thiadiazol-2-yl ureido propionaldehyde

-부틸-1,3,4-티아디아졸-2-일 이소시아네이트 이량체 6g, 3-메틸아미노 프로피온 알데하이드의 디메틸 아세탈 4.0g과 벤젠 50ml의 혼합물을 기계적 교반기와 환류냉각기가 장치된 유리반응 후라스크에 넣는다. 반응혼합물을 환류온도에서 5분간 교반하면서 가열한다. 이 시간후 반응혼합물을 벤젠을 제거하면 잔사가 생성된다. 잔사를 재결정하면 원하는 생성물 3-[1-메틸-3-(5-부틸-1,3,4-티아디아졸-2-일) 유레이도] 프로피온 알데하이드의 디메틸 아세탈이 생성된다.5-

A mixture of 6 g of -butyl-1,3,4-thiadiazol-2-yl isocyanate dimer, 4.0 g of dimethyl acetal of 3-methylamino propionaldehyde and 50 ml of benzene was prepared by a glass reaction flask equipped with a mechanical stirrer and a reflux condenser. Put it in. The reaction mixture is heated with stirring at reflux for 5 minutes. After this time, benzene is removed from the reaction mixture to form a residue. Recrystallization of the residue gives the dimethyl acetal of the desired product 3- [1-methyl-3- (5-butyl-1,3,4-thiadiazol-2-yl) ureido] propion aldehyde.

Example 32

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-하이드록시-2(1H)-피리미딘온의 제조Tetra hydro-1- (5-

Preparation of -Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone

3- [1-methyl-3- (5-butyl-1,3,4-thiadiazol-2-yl) ureido] 16 g of dimethyl acetal of propionaldehyde, 10 ml of concentrated hydrochloric acid and 500 ml of water were prepared with a mechanical stirrer and thermometer. Place in a glass reaction vessel equipped with a reflux condenser. The reaction mixture is filtered when hot and the filtrate is cooled to form a precipitate.

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-하이드록시-2(1H)-피리미딘온이 생성된다.The precipitate is recovered by filtration, dried and recrystallized to give the desired product tetrahydro-1- (5-

-Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone is produced.

Example 33

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-아세탈옥시-2(1H)-피리미딘온의 제조 테트라 하이드로-1-(5-

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-하이드록시-2(1H)-피리미딘온 0.1몰, 초산무수물 0.11몰, 토루엔 설포산 0.05g과 벤젠 100ml을 기계적 교반기와 온도계가 장치된 유리반응 용기에 넣는다. 반응혼합물을 증기욕상에서 2시간동안 교반하면서 가열한다.Tetra hydro-1- (5-

Preparation of -Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-acetaloxy-2 (1H) -pyrimidinone Tetrahydro-1- (5-

0.1 mol of -butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone, 0.11 mol of acetic anhydride, and 0.05 g of toluene sulfoic acid; 100 ml of benzene is placed in a glass reaction vessel equipped with a mechanical stirrer and thermometer. The reaction mixture is heated with stirring for 2 h in a steam bath.

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-아세틸옥시-2(1H)-피리미딘온이 생성된다.After this time, the reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure, leaving a residue. Recrystallization of the residue affords the desired product tetrahydro-1- (5-

-Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-acetyloxy-2 (1H) -pyrimidinone is produced.

Example 34

Preparation of tetra hydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-benzoyloxy-2 (1H) -pyrimidinone

Tetrahydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone 0.05 mole, triethyl 0.06 moles of amine and 50 ml of benzene are placed in a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux cooler.

0.05 mole of benzoyl chloride is added with stirring. After the addition is complete, the reaction mixture is heated with continuous stirring at reflux for 30 minutes. After this time, the reaction mixture is filtered and the filtrate is removed under reduced pressure to give a solid residue. Recrystallization of the residue affords the desired product tetra hydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-benzoyloxy-2 (H) -pyrimi Dion is produced.

Example 35

Preparation of tetra hydro-1- (5-butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-benzoyloxy-2 (1H) -pyrimidinone

-부틸-1,3,4-티아디아졸-2--일)-3-메틸-6-하이드록시-2(1H)-피리미딘온 0.05몰, 트리에틸 아민 0.06몰과 벤젠 50ml을 기계적교반기, 온도계와 환류냉각기가 장치된 유리 반응 용기에 넣는다.Tetra hydro-1- (5-

0.05 mol of -butyl-1,3,4-thiadiazol-2--yl) -3-methyl-6-hydroxy-2 (1H) -pyrimidinone, 0.06 mol of triethylamine and 50 ml of benzene , Into a glass reaction vessel equipped with a thermometer and reflux condenser.

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-but-3-에노일옥시-2(1H)-피리미딘올, 테트라하이드로-1-(5-

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-pent-4-에노일옥시-2(1H)-피리미딘온, 테트라하이드로-1-(5-

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-hex-4-에노일옥시-2(1H)-피리미딘온, 테트라하이드로-1-(5-

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-but-3-이닐옥시-2(1H)-피리미딘온, 테트라하이드로-1-(5-

-부틸-1,3,4-티아디아졸-2-일)-3-메틸-6-hex-4-이노일옥시-2(1H)-피리미딘온 등이 있다.0.05 mole of benzoyl chloride is added dropwise with stirring. After the addition is complete, the reaction mixture is heated with stirring for 30 minutes at reflux temperature. After this time, the reaction mixture is filtered and the filtrate is removed under reduced pressure to form a solid residue. Recrystallization of the residue gave the desired product tetra hydro-1- (5-butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-benzoyloxy-2 (1H) -pyrimidinone. do. Additional compounds within the scope of the present invention prepared by the preparation method of the above examples are tetra hydro-1- (5-ethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6- Acryloyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-propyl-1,3,4-thiadiazol-2-yl) -3-butyl-6-But-3-eno Iloxy-2 (1H)-pyrimidinone, tetra hydro-1- (5-butyl-1,3,4-thiadiazol-2-yl) -3-pentyl-6-Pent-3-enoyljade Ci-2 (1H) -pyrimidinone, tetrahydro-1- (5-pentyl-1,3,4-thiadiazol-2-yl (-3-hexyl-6-hex-4-enoyloxy- 2 (1H) -pyrimidinone, tetra hydro-1- (5-hexyl-1,3,4-thiadiazol-2-yl) -3-pent-3-ethyl-6-pentanoyloxy-2 ( 1H) -pyrimidinone, tetra hydro-1- (5-cyclopropyl-1,3,4-thiadiazol-2-yl-3-hex-4-enyl-6-hexanoyloxy-2 (1H) ) -Pyrimidinone, tetra hydro-1- (5-cyclobutyl-1,3,4-thiadiazol-2-yl) -3-bromomethyl-6-butanoyloxy-2 (1H)- Pyrimidinone, tetra Idro-1- (5-cyclopentyl-1,3,4-thiadiazol-2-yl) -3-trichloromethyl-6-chloro acetaloxy-2 (1H) -pyrimidinone, tetra Hydro-1- (5-cyclohexyl-1,3,4-thiadiazol-2-yl) -3-β-chlorohexyl-6-bromoacetyloxy-2 (1H) -pyrimidinone tetra Hydro-1- (5-cycloheptyl-1,3,4-thiadiazol-2-yl) -3-β-bromoethyl-6-β-crorobutanoyloxy-2 (1H) -pyri Midinone, tetrahydro-1- (5-aryl-1,3,4-thiadiazol-2-yl) -3- (1,1-diethylprop-2-ynyl) -6-cyclopropyl- Carbonyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-but-3-enyl-1,3,4-thiadiazol-2-yl) -3- (1,1-di Propylbrom-2-ynyl) -6-cyclobutyl-carbonyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-4-enyl-1,3,4-thiadiazole-2 -Yl) -3-methyl-cyclopentyl carbonyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-pent-4-enyl-1,3,4-thiadiazole-2- Yl) -3-methyl-6-cyclohexyl-carbo Nyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-hex-4-enyl-1,3,4-thiadiazol-2-yl) -3-methyl--6-cyclo Hexylcarbonyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-chloromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-cycloheptyl -Carbonyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-bromomethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6- (4- Methyl thibenzoyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-trichloromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6- (4 -Ethylthiobenzoyloxy) -2 (1H) -pyrimidione, tetrahydro-1- (5-β-chloroethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6 -(3-propylthiobenzoyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-β-bromoethyl-1,3,4-thiadiazol-2-yl) -3-methyl -6- (3-hexyl thiobenzoyloxy) -2 (1H) -pyrimidinone, tetrahydro-1- (5-W-chlorohesyl-1,3,4-thiadiazol-2-yl)- 3-methyl-6- (3,4,5-trichlorobenzoyljade ) -2 (1H) -pyrimidinone, tetrahydro-1- (5-ethoxy1,3,4-thiadaazol-2-yl) -3-methyl-6- (3-ethyl benzoyloxy)- 2 (1H) -pyrimidinone, tetrahydro-1- (5-propoxy-1,3,4-thiadiazol-2-yl) -3-methyl-6- (4-propylbenzoyloxy-2 ( 1H) -pyrimidinone, tetrahydro-1- (5-butoxy-1,3,4-thiadiazol-2-yl) -3-methyl-6- (4-butylbenzoyloxy) -2 ( 1H) -pyrimidinone, tetrahydro-1- (5-hexyloxy-1,3,4-piadiazol-2-yl) -3-methyl-3- (4-hexylbenzoyloxy) -2 ( 1H) -pyrimidinone, tetrahydro-1- (5-ethylthio-1,3,4-thiadiazol-2-yl) -3-methyl-6- (4-bromobenzoyloxy) -2 ( 1H) -pyrimidinone, tetrahydro-1-(5-propylpio-1,3,4-thiadiazol-2-yl) -3-methyl-6- (4-iodobenzoyloxy) -2 (1H) -pyrimidinone, tetrahydro-1- (5-hexylthio-1,3,4-thiadiazol-2-yl) -3-methyl-6- (2-fluorobenzoyloxy) -2 (1H) -pyrimidinone, tetrahydro-1- (5-ethylsulfonyl-1,3,4-thiadi Zol-2-yl) -3-methyl-6- (2-ethoxybenzoyloxy) -2 (1H) -pyrimidinone, tetrahydro-1- (5-propylsulfonyl-1,3,4-thia Diazol-2-yl) -3-methyl-6- (4-propoxybenzoyloxy) -2 (1H) -pyrimidinone, tetra hydro-1- (5-butylsulfonyl-1,3,4- Thiadiazol-2-yl) -3-methyl-6- (4-hexyloxybenzoyloxy) -2 (1H) -pyrimidinone, tetra hydro-1- (5-hexylsulfonyl-1,3,4 -Thiadiazol-2-yl) -3-methyl-6- (3-chloromethyl benzoyloxy) -2 (1H) -pyrimidinone, tetrahydro-1- (5-ethylsulfinyl-1,3 , 4-thiadiazole-2-methyl-6- (4-trifluoro methylbenzoyloxy) -2 (1H) -pyrimidinone, tetrahydro-1- (5-propyl sulfinyl-1,3,4 -Thiadiazol-2-yl) -3-methyl-6- (4-β-bromoethyl benzoyloxy) -2 (1H) -pyrimidinone, tetrahydro-1- (5-hexylsulfinyl-1 , 3,4-thiadiazol-2-yl) -3-methyl-6-acetaloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-trifluoromethyl-1,3,4 -Thiadiazol-2-yl) -3-methyl-6- Bromoacetyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-β- Chloropropanoyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-trifluoromethyl-1,3,4-thiadiazol-2-yl) -3-methyl-6- β-bromopentanoyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-trifluorotomethyl-1,3,4-thiadaazol-2-yl) -3-methyl-6 -W-chlorohexanoyloxy-2 (1H) -pyrimidine is tetrahydro-1- (5-

-Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-but-3-enoyloxy-2 (1H) -pyrimidinol, tetrahydro-1- (5-

-Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-pent-4-enoyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-

-Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hex-4-enoyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-

-Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-but-3-ynyloxy-2 (1H) -pyrimidinone, tetrahydro-1- (5-

-Butyl-1,3,4-thiadiazol-2-yl) -3-methyl-6-hex-4-inoyloxy-2 (1H) -pyrimidinone and the like.

Substantial use as a preparation compound of the present invention is generally made of a preparation composition consisting of an inactive carrier and a manufacturing active capacity of such a compound. It is to be applied to the weed propagation place by the desired amount as a preparation of such a preparation composition. These compositions may be as solids such as powders, granules or wet powders or as liquids such as solutions, aerosols or concentrates which may be emulsified. For example, the problem can be prepared by mixing and stirring the actives with solid inert carriers such as talc, claysilica, propylide and the like, and granules are usually dissolved in attaful solvents in a suitable solvent to form atapules with a particle size of 0.3-1.5 mm. It can be prepared by incorporating into granular carriers such as guides and vermiculite. Wet powders, which can be suspended in water or oil at any desired concentration of the active substance, can be prepared by incorporating the wetting agent into the concentrated powder composition. In some cases, the active compounds are sufficiently soluble in common organic solvents such as petroleum or xylene and can therefore be used directly in solution in these solvents. Sometimes solutions of herbicides can be dispersed under superatmospheric pressure as aerosols.

However, preferred liquid compositions are lubricable concentrates consisting of a solvent and an emulsifier as the active substance of the present invention and an inert carrier. These emulsifiable concentrates may be diluted with water or oil to the desired concentration of the active substance for application to the weed spread area. The most common emulsifiers used in these concentrates are nonionic surfactants or mixtures of nonions and anionic surfactants. By using an emulsifier, it is possible to prepare a converted emulsion for direct use where weeds are rampant.

Typical herbicide compositions according to the invention are as in the following examples where the dose is parts by weight.

Example 36

Preparation of Powder

Product 10 of Example 5

Powder Talc 90

The components are mixed in a mechanical grinder-mixer and a powder of the desired particles is obtained which can be easily flowed up until homogeneous. This powder is suitable for direct use in weed spread areas.

The compounds of the present invention can be applied as herbicides by conventional methods in the art. One method of weed suppression is to spray a herbicide composition consisting of an inert carrier with a compound of the present invention in an amount that is capable of exhibiting herbicidal activity on the weed as an active ingredient in the weed spread area. The concentrations of the novel compounds of the present invention in the composition of herbicides vary widely depending on the formulation or purpose of use, but generally the herbicide composition contains 0.05-95% by weight of the active compound of the present invention.

More preferred types of herbicide compositions of the present invention contain from about 5-75% of active material.

The composition may contain additional materials such as other fungicides, stabilizers, dispersants, active inhibitors, adhesives, adhesives, fertilizers, active enhancers and the like, such as insecticides, nematodes and the like.

The compounds of the present invention are more useful when mixed with other herbicides or dead solids, growth inhibitors and the same as in the herbicide compositions described above. These other substances may contain 5-95% of the active ingredient in the herbicide composition. The use of these herbicides or acaricides in combination with the compounds of the present invention provides more effective herbicide compositions for weed suppression and sometimes results obtainable as individual herbicides. Weeds are undesired plants that grow in undesired places and are of no economic value and interfere with the production of crops, ornamental plants or breeding of livestock. Weeds include wild liquor, lamb's quarter, nectar, wild grass, wild mustard, field pennyless, poisonous grass, rake, chickweed, wild oat, belbit leaf, purdure, vanyardgrano, a kind of perennial plant, Barkweed, Docomari, Wild Buckwheat, Kochia, Canopy, Concosol, Rackweed, Frog Coopweed, Padu, Coupia, Cactus Grass, Corydalis Grass, Gazette, Hempnet, Naweb, Lighthouse Genus, trefoil, memex, jungle rice, herbaceous plants, asteraceae, chapelweed, morning glory, rake grass, dirk salad, nyad, barley weed, fulpanicum Year-round, such as datura, witchgrass, witchgrass, fish tank, tiweed, wild turnip and sprenkle top; Wild carrots, matricaria, wild barley, cauliflower, yellow-headed radish, burdock, hawthorn, biennial plants such as round leaf mallow, vulture, marsupial, moss murinein, and purple star thistle; Or white cockle, perennial barley, cokergrass, johnsongrass, canadatis, hedge bindweed, bermudagrass, chivesorel, quiridok, nutgrass, field cheekweed, dandelion, bellflower, field bindweed, rushonnaedweed Shrubs, herbarium, horsefly, hydrangea, grompon, genus plants, ironward, sesbania, reeds, buds, winter-cress, hosnerol, nutsage, perennial plants and perennial plants such as sicopod Kinds of weeds are known including water. Similarly such weeds are classified as broadleaf weeds or grassy weeds. It is economically desirable to inhibit the growth of such weeds without damaging beneficial plants or grasses.

The new compounds of the present invention are particularly valuable for weed control because they are relatively nontoxic to many beneficial plants, while being toxic to many weeds. The exact amount of compound required depends on several factors, such as the strength of the specific weed species, the climate, the type of soil, the method of application, and the types of beneficial plants in the same area.

Thus, application of up to 1-2 ounces of active compound per acre is sufficient to suppress the auctioned rampant of weeds growing under adverse conditions and application of 10 pounds or more of active compound per acre is a seasoned perennial weed that grows under favorable conditions. It may be necessary to suppress the rampant spread.

The herbicidal toxicity of the new compounds of the present invention can be explained by many known test techniques, such as pre- or post-germination tests.

Preparative activity of the compounds of the present invention has been demonstrated by experiments conducted for the inhibition of germination of various weeds. In these experiments, small plastic greenhouse pots filled with dry soil were sprayed with various types of weed seeds. After seeding the pots, water was sprayed for 24 hours or less until the soil became wet, and the test compound made of an aqueous emulsion of acetone solution containing an emulsifier was sprayed at the concentration indicated on the surface of the soil. After spraying, the soil container was placed in a greenhouse to provide the required heat and watered daily or occasionally. The plants were kept under these conditions for 21 days and the condition of the plants and the degree of damage to the plants were then evaluated on a scale of 0-10 as follows.

0 = No damage, 1,2 = Slight damage, 3,4 = Normal damage, 5,6 = Severe damage, 7,8,9 = Severe damage, 10 = Test

The effect of the compound is demonstrated by the data shown in the following table (I).

The herbicidal activity of the compounds of the present invention has also been demonstrated by experiments conducted for inhibition after germination of various weeds.

The compounds to be tested in these experiments were formulated with aqueous emulsion and sprayed with the indicated doses on the weed leaves of constant size. After spraying, the plants were placed in a greenhouse and watered daily or often. Water was not given to the leaves of treated plants. The extent of damage was measured 14 days after treatment and rated 0-10 as described above.

The effect of this compound is demonstrated by the data shown in the following table (I).

TABLE 1

Claims (1)

The compound of formula (V) is then heated in a dilute aqueous acidic reaction medium to prepare a compound of formula (II), or the compound of formula (II) at 50-90 ° C. in the presence of a catalytic amount of toluenesulfonic acid A method of preparing the following compound of formula (I) by reacting with an acid anhydride of II) or by reacting the following compound of formula (II) with a compound of formula (IV) at 10-30 ° C. in the presence of an acid acceptor.

Wherein R ¹ is alkyl, alkenyl, haloalkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl or cycloalkyl and R ² is alkyl, alkenyl, haloalkyl or

And R ⁴ and R ⁵ are each hydrogen or alkyl and R ⁶ is alkyl, haloalkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl or

X is alkyl, halogen, haloalkyl, nitro, cyano or alkoxy, m and n are each an integer of 0-3 and R ⁷ and R ⁸ are methyl or ethyl.