TW387883B - Intermediates for the preparation of 2-imidazolin-5-ones - Google Patents

Description

A7 B7 V. Description of the invention (The present invention relates to novel products which can be used as intermediates of 2-dihydroimidazol-5 · one for the preparation of bactericidal fungi. The present invention also relates to methods for preparing these novel products, and from this And other novel intermediates to obtain 2-dihydropyridine-5-net. 2-dihydroimidazol-5-one is known for its fungicidal activity, especially see European Patent Application No. 551,048 No. 599,749 and No. 629,616, and see International Application No. WO 93/24467. One object of the present invention is to propose novel intermediates for the preparation of these 2-dihydroimidazol-5-ones. Another object is to propose a novel way to obtain the bactericidal 2-dihydroimidazol-5-one with improved safety. The present invention thus provides 2-dihydroimid-5-one of the general formula (I). ... "(Please read the note on the back before this page)

(I)-In the formula of the Central Bureau of Standards and ψ 'Cooperative, -R1 is a C1-C3 alkyl or phenyl group, and -R2 is an aryl group selected from phenyl or pyridyl, and if necessary, selected from a halogen atom 'One to three groups of nitro or cyano are substituted, and C1-C3 alkyl or CL · C3 alkoxy; except for 4-ethyl-4-phenyl_2-thiotetraamine. The subject matter of the invention is also the salt-formed form and stereoisomers of the compound of formula (I). In particular, 'the main body of the present invention is optical from asymmetric carbon -4- The paper size is applicable to China National Standard (CNS) A4 specification (2 丨 0X297 mm) 5. Description of the invention (2) A7 B7 The isomers are printed by the Shell Standard Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. The most special is that if the R1 & R2 groups are different, the optical isomers come from the asymmetric carbon. These optical isomers are optically pure compounds or compounds enriched in a mirror image isomer. In the following, the optically active compound that is rich in a predetermined image isomer is referred to as a compound containing at least 80% (preferably at least 90%) of this image isomer. All of these compounds are included in the above formula (1). Among the compounds of formula (I), the following are preferred: • R1 is a C1-C3 alkyl group, and -R2 represents a phenyl group, optionally substituted with a halogen atom, a cyano group, or a nitro group, or a methyl group or a methoxy group . _ More specifically, among the compounds of formula (I), R2 is a phenyl group and R1 is a fluorenyl group. According to a very advantageous transformation of the present invention, the compound of formula () is: -R1 is a methyl group, and -R2 is a phenyl group, which are mirror image isomers of the asymmetric carbons connected to R1 and R2. In this article, all the radicals in the chemical formulas described below, and the radicals defined in the general formula (〗), have the same meaning unless otherwise specified. In the scope of this specification, including subsequent patent applications, alkyl groups and partial groups may be straight or branched. A mode for preparing the compound of formula (I) is described. This mode of preparation is for compounds in which the carbon attached to the base of R1 and R2 is racemic. However, those skilled in the art will use these same reactions to obtain the compound of formula (1) which docks R1 & R2 as a mirror image isomer. The reason for this is that the following reactions are completely -5- (Please read the notes on the back before you go to this page)-Binding, binding-thread ^ 7. Jingyang Biaomu Cooperative Cooperative V. Description of the invention (3) A7 B7 Selectivity, that is, no change in this absolute configuration of the same carbon. The compound of formula (I) can be obtained by reacting the compound of formula (II) with carbon disulfide in a solvent or a solvent mixture as needed, and in the presence of a base at a temperature of οι to +50 ec, according to the following figure 0 (II) CS, 0, NFh-〇-SH% m

(I) In the formula, R3 is an amine group or a hydroxyl group, or an alkoxy group having t to 6 (preferably to 3) carbon atoms, or a benzyloxy group substituted with an _ atom if necessary. The base used as required may be an inorganic base such as an alkali metal or alkaline earth metal hydroxide or a salt of a broken acid, or an organic base such as a primary, secondary or tertiary amine. The base / compound II ratio (expressed in moles) is from 0.05 to 1_2, preferably from 0.1 to i. In this figure, the compound of formula (III) can be isolated into an intermediate, and if a base is used, it can be in the form of a salt. The solvents that can be used are water, ethers, cyclic ethers, alkyl esters, dipolar solvents such as 6 · nitrile, alcohols and aromatic solvents with 1 to 4 carbon atoms, preferably toluene , Two gas methyl or gas imitation, and carbon disulfide. The solvent mixture that can be used is a mixture of one or more alcohols and one or more of the above solvents. If R3 is a base, water is preferably used as the solvent β. If R3 is not a hydroxyl group, an alcohol / water mixed solution is preferably used as the solvent. -6- This paper size is applicable to the Chinese National Standards of Standards (CNS) Bagu ^ grid (2 丨 〇 > < 297) (Please read the precautions on the back before Jr, J € this page) Printed by the central and central bureau of Shellfish Consumer Cooperative Co., Ltd. A7 ---- B7 V. Description of the invention (4) When the compound of formula (III) is isolated, it can be directly heated and converted at 25, c to the reflux temperature of the solvent used. The compound (J. intermediate compound (111) is converted into compound (I), which can be treated by treating a strong acid with an inorganic acid such as hydrochloric acid or sulfuric acid, or an organic acid such as trifluoroacetic acid. This process is preferred to the absence of an alkali or 20 To 40T: at temperature. In this process, the compound of formula (III) was not isolated. · Another procedure for preparing compound (J) from compound (Π) is described in AC Davis and AJ, Levy Journal of the Society (J. Chem. Soc.) 2419-25 (1951) or κ · Hofmann waiting for the Journal of the American Chemical Society (j. Am. Chem. Soc), Volume 74, 470 ~ 47 6 pages (1952) ). The α-amino ester of formula (II) (wherein R3 is an alkoxy group) can be obtained according to M. Brenner and W. Huber. Chemistry and Technology (Helv Ch.

Acta (1953), Vol. 36, pp. 1109 ~ 1115, a similar procedure is described in which the corresponding α-amino acid is subjected to an esterification reaction. The obtaining of aminoamidoamine of formula (11) (wherein R3 is an amine group) can be described according to JA Garbarino's Ann. ChiMca ItaL, Volume 59, pages 841 ~ 849 (1969) From the role of amino esters to ammonia. α-Amino acids are prepared according to reactions and methods known per se. If the compound of formula (II) is an amine ester mirror isomer, it is specifically obtained from the following:-According to RS Atkinson et al., Tetrahedron, 1992, No. 48, 7713-30, formerly asymmetric (Prochiral) compound undergoes non-mirror selective amination reaction, and then, asymmetric coupling via deprotection reaction, or this paper size applies China National Standard (CNS) A4 specification (210X297 mm) ------ ^-; --- install-* \ 1 ·: (Please read the precautions on the back before f is X) Order V. Description of the Invention (5)-According to Y. Sugi and S. Mitsui Bulletin of the Society

Chem, Soc. Japan), 1969, "Liao period" pages 2984-89, corresponding to the dissociation of racemic mixtures from asymmetric compounds, or-according to DJ Cram et al. Journal of the American Chemical Society, 1961, period On pages 2183-89, the asymmetric amino acid undergoes esterification, and the compound of the right formula (II) is an amine-based amine mirror isomer. 'According to H. Dahii et al., Swiss Chemical Journal, Vol. 53, 1370 ~ ; The description on page 1378 (1970) is obtained starting from the asymmetric amino ester, or by dissociation from the corresponding racemic mixture. 2-thiotetrahydrothiazol-5-one of formula (I) is used to prepare bactericidal formula (ιν) 2_dihydroimidazole-5 · one,

R4 (IV) where -M represents a TF oxygen or sulfur atom; -R30 represents a straight or branched chain containing 1 to 6 carbon atoms; a radical, or a straight or branched chain containing 1 to 6 carbons _Alkyl of the atom; -R4 represents an interest atom or an aryl group; -R5 represents an aryl or heteroaryl group selected from the group consisting of phenyl, fluorenyl, amidinyl, pyrimidinyl, daphnyl, pyrhyl, Pyrimidyl, benzopyrimyl, furanyl, phenylsulfanyl, p-ringyl, isophenyl, or methylenedioxyphenyl groups, each of which may be carried through from 1 to 7 groups, as required, Preferably, i to 3 are selected from R51 -8-"Paper Standard (CNS) 8 4 (210X297 mm)" in this paper for New Year's Eve —'— ~: -------- V. Description of the invention (6 A7 B7) The same or different groups may be substituted as defined by the Ministry of Justice and the Central Bureau of Cooperatives, as shown below;-R51 means:-halogen atom or-straight or branched chain containing 1 to 6 Carbon alkyl, alkyl, alkoxy, alkoxy, alkylthio, alkylthio or alkylsulfonyl, or-cycloalkyl containing 3 to 6 carbon atoms, cycloalkane , Alkenyloxy, alkynyloxy, sulfanyl or alkynylthio, or -terminal or cyano , Or-amine group, if necessary, mono- or di-substituted by an alkyl or fluorenyl group of 6 to 6 carbon atoms or an alkoxycarbonyl group of 2 to 6 carbon atoms; and the compounds and their stereoisomers "Agriculturally acceptable salt formation" In particular, if R1 and R2 are different, they are optical isomers derived from the presence of asymmetric carbons connected to the R1 & R2 group. The description is based on the racemic series or mirror image. The structure series method starts from the main formula (1) 2-thiotetrahydropyrazol-5-one of the present invention to prepare a fungicidal compound of formula (IV). The compound of formula (I) and the compound of formula (V) are generally The reaction is carried out in a solvent at a temperature of + 20 * c to +100 ° C (preferably 40 to 80. (:)) according to the following figure.

k (V) h2s (VI) n Solvents that can be used are, for example, dihenane, dipolar aprotic solvents, in particular, N-methylpyrrolidone 'dimethylformamide, dimethylsulfoxide or acetonitrile, -9- This paper uses Chinese National Ladder Standard (CNS) A4 size (210X297mm) for this paper. Duo printed A7 B7 cooperation with the Central Government Bureau of the Ministry of Economic Affairs. 5. Description of the invention (7) Including 1 to Alcohols (more specifically methanol) with 4 carbon atoms' aromatic solvents (more specifically-designated as V »bito or monogas benzene). The catalyst preferably used for this reaction is selected from a third amine such as triethylamine or tributylamine, or an organic salt of this amine such as tributylamine acetate. This catalyst is usually present at a catalyst / compound (I) ratio (expressed in moles) of 0.05 to 1 (preferably 0.1 to 0.5). In this way, an increased purity is obtained. Thiothelide urea of formula (VI) is converted to 2-dihydroimidazol-5-one of formula (IV) according to the method described in one of the patent applications EP 551,048, EP 599,749 and EP 629,616. The following examples are only used to illustrate the compounds and preparation methods of the subject of the present invention, and in no way limit the scope of the present invention. The derived structures described are established by at least one of the following spectroscopic techniques: proton NMR spectrometry, carbon 13 NMR spectrometry, infrared spectrometry, and mass spectrometry, and customary methods for measuring optical rotation. Example 1: Preparation of (4S) _4-fluorenyl-4-phenyl-2-thiotetrahydrooxazole-5-fluorene from amidoamine 3.26 g (20 milliwatts) of (2S) -2-amino- 2-Phenylpropanamine, 6 ml (100 mol) carbon disulfide and 4 ml acetochloride were put into a 50 ml round bottom flask equipped with a mechanical stirrer. This heterogeneous medium was continuously stirred at 20eC for 20 hours. Excess carbon disulfide and acetonitrile were subjected to vacuum distillation, and then purified and purified to obtain 3.70 g of (4S) -4-methyl-4-phenyl-2-thiotetrahydro-P-sep-5-one as a white solid. Melting point is 104 eC, yield is equivalent to 83%. Real Example 纟: Preparation of (4S) _4-methyl-4-phenyl-2-thiotetrahydrooxazole-5-one-10- from amine esters This paper is applicable to Chinese standards (CNS) A4 Specifications (210X297mm)-'~~ --- (Please read the note on the back, then 0, > v this page) > equipment_ order_

-Line C 387883 A? ____ B7 V. Description of the invention (8) 2 g (11.1 ¾ ear) (2S) -2-amino-2-phenylpropanoic acid methyl vinegar, 5 ml tetrahydrofuran, 1.82 ml (13 mmol) Mol) triethylamine and 078 ml (13 mmol) carbon disulfide were put into a 25 ml test tube equipped with a magnetic stirrer. After sealing, the test tube was kept at 45 ° C, and the homogeneous medium was continuously stirred at this temperature for 4 hours. After cooling and purification ', 2 g of (4S) _4-methyl_4_phenyl · 2-thiotetrahydropyrazole-5 -one was obtained as a white powder with a yield of 80/0. Actually, H: Preparation of (4S) _. 4 · methyl-4-phenyl-.1-anilino-2-thiohydantoin urea 893 mg (4 pen moles) (4S)-4 -methyl- 4-Phenyl-2-thiotetrahydrou cejun _ 5-one, 8 ml of acetonitrile and 100 ml (0.4 mmol) of tributylamine were input into a 25 ml round-bottomed flask equipped with a magnetizer. . The mixture was warmed up, and then a solution of 520 mg (4.8 mmol) of phenylhydrazine in 4.5 ml of acetonitrile was added for 2 hours. The reaction medium is heated at 80 ° C for 6 hours. After cooling, acetonitrile was removed by distillation under reduced pressure. After purification, 975 mg of (4S) -4-methyl-4 · phenyl-1-anilino-2-thioethyllactone urea was obtained as a white solid with a melting point of 167.0 and a purity of 100 as determined by HPLC. %, That is, a yield of 82%. Example 4: Preparation of (4S) -4-methyl-4-benzyl-2 · thiotetraamine pseling · 11-gram (1) from (2S) -2-amino-2-phenylpropionic acid (1 0.2 mole) (2S) -2-amino-2-phenylpropionic acid (or a mixture containing 15% by weight amino acid in solid NaCl), 10 ml of N-fluorenylpyrrolidone, 0.8 g ( 2. ΗΓ2 mol) sodium hydroxide pellets, followed by 1.8 ml (3. Γ 2 mol) of carbon disulfide, sequentially input into a 50 ml round bottom flask equipped with a magnetic stirrer. After sealing, the reaction medium is heated under intense stirring at 60 ° C for 5 hours. -11-The paper's A degree applies to the Chinese standard (CNS Μ4 ^ «· (210X297 mm) 337833 a? B7. V. Description of the invention ( 9) After cooling, add 50 ml of water and then 5.4 ml of concentrated sulfuric acid to the reaction medium. The organic phase is extracted, washed, dried, and concentrated. (4S) -4 -methyl-4- Phenyl-2-thiotetrahydrooxazole_5_one, yield 84%. (Please read the precautions on the back before r is this page.) -12- This paper size applies to Chinese national standard (CNS > A4 size (210X297 mm)

Claims (1)

Patent Application No. 8611420_Shao Chinese Application for Patent Fan Laimengchui (February 88) ICS 38 * 7883 D8 Supplementary Scope of Patent Application. 2.12 Printed by Shellfish Consumer Cooperative, Central Standards Bureau, Ministry of Economic Affairs C-SH% (III) ' 2-thiotetrahydropyrazole-5 _ones of the general formula (I) (I) In the formula, -Ri is a C1 or C3 alkyl group, and -R2 is a phenyl group; and a salt-formed form and a corresponding stereoisomer, in particular, because of the presence of an asymmetric carbon with R2 Optical isomers appear. 2. The compound according to item 1 of the scope of patent application, characterized in that Ri is methyl. 3. The compound according to item 1 or 2 of the scope of patent application, which is characterized as a mirror image isomer relative to an asymmetric carbon with 1 ^ and 112. 4. A method for preparing a compound of formula (1) according to item 1 or 2 of the patent application, characterized in that the compound of formula (II) and carbon disulfide are in a solvent or a solvent mixture in the presence of a base if necessary The reaction is carried out at a temperature of 〇 " c to + 50 ° C according to the following: ..W .r3 + cs: — (Π) where 'R3 is an amine group or a hydroxyl group, or one containing 1 to 6 carbon atoms Straight chain or NT,-.: --------- Private ------- Order ------ Line ί (Please read the precautions on the back before filling this page) Patent No. 86104420 Application_Shao Chinese Application for Patent Fan Laimengchuiben (February 88) ICS 38 * 7883 D8 Supplementary Scope of Patent Application. 2.12 Printed by Shellfish Consumer Cooperative, Central Standards Bureau, Ministry of Economic Affairs, ΝΗ-C-SH% (III) ' 2-thiotetrahydropyrazole-5 _ones of the general formula (I) (I) In the formula, -Ri is a C1 or C3 alkyl group, and -R2 is a phenyl group; and a salt-formed form and a corresponding stereoisomer, in particular, because of the presence of an asymmetric carbon with R2 Optical isomers appear. 2. The compound according to item 1 of the scope of patent application, characterized in that Ri is methyl. 3. The compound according to item 1 or 2 of the scope of patent application, which is characterized as a mirror image isomer relative to an asymmetric carbon with 1 ^ and 112. 4. A method for preparing a compound of formula (1) according to item 1 or 2 of the patent application, characterized in that the compound of formula (II) and carbon disulfide are in a solvent or a solvent mixture in the presence of a base if necessary The reaction is carried out at a temperature of 〇 " c to + 50 ° C according to the following: ..W .r3 + cs: — (Π) where 'R3 is an amine group or a hydroxyl group, or one containing 1 to 6 carbon atoms Straight chain or NT,-.: --------- Private ------- Order ------ Line ί (Please read the notes on the back before filling in this page} 888 ^ ABCD 387883 The scope of the patent application is branched alkoxy group, or a benzyloxy group substituted with a halogen atom as required. 5. The method according to item 4 of the patent application scope, characterized in that R3 is an amine group or a hydroxyl group, or contains 1 to 3 carbons Atomic linear or branched alkoxy groups, or benzyloxy substituted with south atoms if necessary. 6. The method according to item 4 or 5 of the scope of patent application, characterized in that it is in the absence of a base or 20 to 40 ° C. 7 · A method of converting a compound of formula (I) according to item 1 or 2 of the patent application park, characterized in that the compound of formula (I) and formula (V ) The compound is reacted in a solvent at a temperature of + 20t to + 100 ° C according to the following figure, --------- ^! (Please read the note on the back before filling this page) 0 (I) (V) xVs + (VI) ^ h2s, wherein -R4 represents a hydrogen atom or a magnetic group; -Rs represents an aryl group or a heteroaryl group selected from the group consisting of phenyl, distillyl, and pyridyl , Pyrimidinyl, daphnyl, pyridinyl, pyrenyl, benzophenone ', succinyl, benzofuranyl, quinolinyl, isoquinolinyl, or methylenediphenyl, these are free If necessary, Ginger is replaced by 1 to 7 bases that are the same or different; -R51 means: -halogen atom, or -2- private paper standard (CNS) A4 Specifications (210X297 mm) Line Γ. Printed by the Central Government Bureau of the Ministry of Economic Affairs and the Industrial and Consumer Cooperatives «. 337883 Patent application scope A8 B8 C8 D8 6 carbon atoms alkyl, haloalkyl, alkoxy, alkoxy, alkylthio, alkylthio or alkanesulfonyl, or-cycloalkyl containing 3 to 6 carbon atoms, Cycloalkyl, alkenyloxy, alkynyloxy, bromothio, or alkynyl, or -Shoryl or Gasoyl * or -Amine 'alkyl or fluorenyl radicals of 1 to 6 carbon atoms as required Or 2 Alkoxycarbonyl groups of up to 6 carbon atoms are mono- or di-substituted. 8. The method according to item 7 of the patent application park, characterized in that the reaction is carried out at a temperature of 40 and 80 ° C, and & is substituted with 1 to 3 substituents. The method of item 7 or 8 is characterized in that it is performed in the presence of a catalyst selected from a third amine or an organic salt of this amine, and the content of the catalyst is such that the catalyst / compound (;) ratio is 〇〇 5 to 10. The method according to item 9. of the patent application, characterized in that the catalyst is triethylamine, tributylamine or tributylamine acetate, and the content of the catalyst is such that the catalyst / compound (I) ratio From 0.1 to 0.5. -3- This paper is in use • National «Ratio (CNS) A4 Size (210x297 mm) (Please read the precautions on the back before filling out this page)-^ 线