Method of obtaining n-substituted 3-cycloalkylsulfonyl-pyrolydion-2,5

专利摘要:
A fungicidal compound of the formula: <IMAGE> (I) wherein A is C5-10 cycloalkyl, R is hydrogen, C1-6 alkyl, phenyl optionally substituted by one or more groups selected from C1-4 alkyl, nitro, hydroxy, carboxy, sulfo, sulfonylamino, halogen, C1-4 alkoxy, C1-4 acyloxy, C2-5 alkoxycarbonyl, C1-4 acyl, and N-(C2-5 alkoxycarbonyl)-sulfonylamino, or phenyl-(C1-4 alkyl) or a salt thereof.
公开号:SU1165231A3
申请号:SU813322502
申请日:1981-08-12
公开日:1985-06-30
发明作者:Шереш Ене；Варконьи Эрика；Вираг Шандор；Кульчар Габор
申请人:Хиноин Дьедьсер Еш Ведьесети Тремекек Дьяра Рт (Инопредприятие)；
IPC主号:

专利说明:

The invention relates to the preparation of iovyos 3-cycloalkylsulphonylpyrrolidinedione-2,5 derivatives, showing fungicidal activity. The formation of the pyrrolidine -2,5-one cycle is known by the closure of the corresponding polyamide when heated ij. The purpose of the invention is to develop on the basis of a well-known method for the preparation of new compounds with an increased fungicidal effect. The delivered del is achieved by the fact that according to the method of obtaining N-substituted 3-cycloalkylsulfonyl pyrrolidinedione-2.5 of the general formula $ 0, A,, (Where A is cyclopentyl or cyclohex R is ethyl, hexyl, phenyl, benzyl, tolyl, 4-methyl -2-sulfophenyl, 3,4-methyl-dioxyphenyl, 4-methyl-3-carboxyphenyl, 4-methyl-2-hydroxymethylphenyl or phenyl, substituted in the position of 4 methyl, labels si-, aminosulfonyl-, ad-TIL-, ethoxycarbonylaminosulfonyl- or by sulfo group, in position 2 by chlorine, and in position 3 by the nitro group, polyamide cycloalkylsulfonyl succinic acid of the general formula CHj-CH-SOi-A (and i I B D where A has the indicated meaning; B and D are substituents, one of which is a hydroxyl group, and the other is a group pa - NH-R, where R has the indicated values, is subjected to dehydration with acetic anhydride in the presence of no aqueous sodium acetate. Compounds of general formula (I), which are formed during the reaction, are precipitated from the reaction mixture and can be separated from the reaction mixture by filtration or centrifugation, or remain in solution. In the latter case, the reaction mixture is usually treated in such a way that the by-products present in some cases are separated by filtration, then the reaction mixture is poured, for example, onto ice, after which the product is separated. According to another method, the volatile components and solvent are removed by distillation from the reaction mixture, and the resulting residue is purified, for example, by recrystallization. Example 1. 1-Phenyl-3-cyclohexylsulfonylpyrrolidinedione-2, 5. 3.39 g (0.01 mol) of 2-cyclohexyl sulfonate 1-4-phenylamino-4-oxobutanoic acid is dissolved in a mixture of 20 MP of acetic anhydride and 0.82 g (0.01 mol) of anhydrous sodium acetate and the reaction solution is heated in for 1 h at 100 ° C. Then the reaction mass is poured onto crushed ice and the indicated compound precipitated out is separated by filtration, after which, washing with water, the acid is removed from it. As a result, 2.76 g (86%) of the title compound with a mp. 149-151 s. After recrystallization from methyl alcohol, the product has so pl. about 150-152 ° C. The minimum inhibitory concentration in the case of Trichbphyton men- tagrophytes 2.5 µg / ml, in the case of Trichophyton floccosum is 1.0 µg / ml. The following compounds can also be obtained by these methods: 1-Ethyl-3-cyclohexylsulfoNylpyrrolidinedione-2, 5, yield 47.6%, m.p. 118-120 0. 1 -CH-Hexyl-3-cyclohexylsulfonylpyrrolidinedione - 2, 5, yield 39.8%, so pl. 127-130 ° C. 1- (2-Chlorophenyl) -3-cyclohexylsulfonylpyrrolidinedione-2, 5, yield 71.4%, so pl. 153-155 ° C. 1- (3-Nitrophenyl) -3-cyclohexylsulfonylpyrrolidione-2, 5, yield 92%, so pl. US-Ue c. 3 1- (4-Acetoxyphenyl) -3-cyclohexylsulfonylpyrrolidinedione-2, 5, 79.1% yield, tg. 203-206 ° C. 1- (4-Sulfoaminophenyl) -3-cyclohexylsulfonylpyrrolidinedione-2, 5, yield 71.8%, mp 208-210 ° C. 1- (4-Methoxyphenyl) -3-cyclohexyl sulfonylpyrrolidinedione-2.5, yield 85.7%, mp. 139-140s. (N-Ethoxycarbonylsulfonylamino) -phenyl-3-cyclohexylsulfone-pyrrolidinedione-2, 5, yield 42.6%, mp. 115-I8 ° C. 1-Benzyl-3-cyclohex lsulfonylpyrrolidinedione-2, 5, yield 84%, t. GO1. 160-162 C. 1-Phenyl-3-cyclopentylsulfonylpyrolidinedione-2.5, yield 60.2%, so pl. 158-159s (from ethyl alcohol). . 1- (P-Tol l) -3-cyclopentylsulfonylpyrrolidinedione-2, 5, yield 86.1%, mp. t78-180 С (after recrystallization from ethyl alcohol). 1- (And Sulfophenyl) -3-cyclohexylsulfonylsrrolidindione-2, 5, yield 56.2%, so pl. 230-236 C. 1- (4-Methyl-2-sulfophenyl) -3-cyclohexyl 1 sulfonylpyrrolidiophene-2, 5 yield 53, tZ, so pl. 244-247 s. 1- (3,4-Dioxyphenyl) -3-cyclohexylsulfonylpyrrolidinedione-2, 5, yield 91.8%, mp. 186-188 ° C. 1- (4-Methyl-3-carboxyphenyl) -3-cyclohexylsulfonylpyrrolidinedione -2.5, yield 46.7%, mp. 184-188 0. 1- (4-Methyl-2-hydroxymethyl-1) -3-schistelohexypsulphonylpyrrolidinedione -2.5, yield 86.2%, P.PL. 174-177c. EXAMPLE 2. 1 (P-Tolsh1) -3-cyclohexylsulfonylpyrro-Shdin-2, 5 -dioi. ; 2.82, g (8 mol) of 2-cyclohexylsul background-4- (p-tolylamino) -4-oxo-butyric acid in 10 MP dimethyl forms and mixed with 1.0 g of pentooxide phosphorus, then added dropwise | 0 , 3 ml of concentrated sulfuric acid. The mixture is heated to and kept at this temperature for 2 hours. The reaction mixture is evaporated to dryness and the remaining thick oil is diluted with a small amount of methanol. Obtain 1.26 g (47%) of 1- (L-tklk) -3-1Shkloheksylsulfonylpyrrolidii-2, 5-dioia. T.SH1. 170-171 ° C (krnstashshz &amp; from methanol). 314 EXAMPLE 3. 1- (4-Ethylphenyl) -3-cyclohexnylsulfonylpyrrolidin-2, 3-dione. 3.66 g (10 mmol) of 2-octylohexylsulfonyl-4- (4-ethylphenylamino) -4-hydroxybutyric acid are mixed with 60 ml of xylene and 3 ml of phosphorus trichloride are added dropwise with stirring. The reaction mixture is heated to with stirring for 20 minutes, then filtered and the filtrate is concentrated under a vacuum. The residue is taken up in ether and filtered off pol.u1 (Enn1y white crystalline material. Obtain 2.17 g (62%) of 1- (4-tsm1phenyl) -3-cyclohexn1sulfonylpyrrolidin-2, 5-dione. So pl.153156 ° ( crystallized from methanol.) Example 1. 1- (i-Tolyl) -3-Cyclohexylsulfonylpyrrolidin-2, 5-dione .3, 53 g (10 mmol) 2-cyclohexiplsulfonyl-4- (and-tolylamino ) -4-hydroxybutyric acid in 30 ml of anhydrous dichloromethane is cooled down with stirring until. While stirring and at a temperature of 0-5 ° C, 1.19 g (11 mmol) of ethyl chlorofurky acid are added dropwise. The temperature is slowly is raised to 30 ° C and the reaction mixture is slowly stirred at this temperature for an additional 30 minutes, the spent product is separated out and the filtrate is taken up to dryness 1.72 (51%) of 1- (| 7-tolyl) -3-cyclohexylsulphoshpyrrolidin-2, 5- Diona. T. PL ITO-HI C (mold out methanol). New measured at position t derivatives of Z-cycloalkenesulfonylphenol rolidindione-2.5, corresponding to the general formula (1), due to the presence of strongly pronounced fungicidal activity used as biologically active substances in fungicidal preparations. The fsgcicidal activity of the new compounds of the general formula is investigated as follows. The nutritious soil is inoculated with. With 10 mp microbes and germinated me, the fungi are examined after 24, 48,. 72, 144 and 288 h, then determine the minimum inhibitory concentration. The results are presented in Table. 1 and 2.
The following organisms were investigated in the tests:
Saccharomyces
cereyisiae OKI 1282 1
CandidaS
albicans. CBS.562 2
Candida
tropicalls CBS, 433 3
Aeperpillus
niger CBS.12648 4 0
Aspergillus
niger SSMG-330 20
Aspergillus
fumigatus CBS.11326 - 5
Aspergillus5
flairis CBS.24765 6
Penicillium
digitatum CBS.31948 7
Penicillium
digitatum SSM.G-382 8 20
Penicilliuin
chrysogehum CBS.19646 9
Penicillium
chrysogehum CCM.F-362 10 Microsporum,
gypseum
var vinosum CBS.10064 11. Sporetrichum
schenfii CBS.34033 12
Trichephyton30
rubrum CBS.30338 13
Trichophyton
roentagrophytes CBS.50148 14
Epidermophyton
floccosumOKI / IV 15 h5
Fusarifira
graminorum DSM.11802 16
Fusariura
oxysporum DSM.10975 17
Fusarium40
raoniliforme DSM. 11778 18
Fusarium
sy1 yugite DSM. 11425 19
Candida
krusei79 / K47
Cryptococcus
neoform78 / K16 22
In tab. Figures 1 and 2 instead of the names of microorganisms are numbers that are located next to the names. so
Fasheni used in the names of microorganisms: CBS. Centralbureau voor Schimmelcultures, Vern, the Netherlands; SSM CzichoSlovak Collecticnof Microorganism, I.E.Pyr- 55 kyne University, Czechoslovakia, Bmo; DSM,
Deutsche Samralung.fur Mikroorganismen, Institution of Mycology Berlin, Germany, Federative Republic of Germany, - OKI .: Orszages K3zeg szzeV, tan Intizet, Budapest.
When administered intraperitoneally, the LDjo value of N-phenyl-3-cyclohexylsulfonylpyrrolidindione-2, 5, determined on female mice, is 382 mg / kg, and determined on male mice - 61 mg / kg.
When used per os, the compounds do not exhibit toxicity. "
In tab. Figure 3 shows the minimum inhibitory concentrations of 1 - ((1-tolyl) -3-cyclohexylsulfonylpyrrolidinedione-2, 5, µg / ml of medium, after 24 and 48 hours after the most important pathogenic fungi.
The indicated minimum inhibitory concentrations completely inhibit the development of microorganisms. Sabourod was used as a nutrient.
1- (p-tolyl) -3-tsiklogeksilsulfrnilpirrolidindion-2, 5 and 1-feniltsiklogeksilsulfonilpirrolidindion-2, 5 also have activity against the following phytopathogenic fungi: Botrytis cinerea, Ascochy ta pisi, Carcospora beticola, Taphrina deformans, Phytophtera infestans, Sclerotinia Sclorotiorum, Verticillium alsoatrum, Verticiliiu dahliae, Venturia.
The most preferred target compound of the present invention is 1- (p-tolyl) -3-cyclohexylsulfonippyrrolidin-2, 5-dione (compound A).
For comparison, the following compounds are taken:
Chlorotrimazole: 1- (2-chlorophenyl) -diphenyl-methyl -1H-imidazole (compound B).
Toliaftate: | N-methyl (N-AL-tolyl) -thiocarbamic acid naphthyl ester (compound C).
The results of comparative experiments are given in table. four.
As can be seen from the above data, representatives of the compounds of formula (1) have higher efficacy against fungi, causing a greater proportion of fungal diseases than known fungicides ..
Table 1
75 50 75
75 50 75
9 75 50 75 10 10 50 75 10 50
150150
150200
150200
2550
5050
75150
150200
2525
75100
2.5
1010 25
2.5 10
1 2.5 10
10 75 75
75 75
150 200 150 150
10 25
10 25
10 10
25 25
- l
25 50
75
10 10
ten
25 2.5
25 2.5 2.5
5 5 5
.Table 4

权利要求:
Claims (3)
[1]
METHOD FOR PRODUCING N-SUBSTITUTED 3-CYCLOAPKILSULPHONIPPYROROLIDINDione -
[2]
2.5 General formula (I)
R where A is cyclopentyl or cyclohexyl;
R is ethyl, hexyl, phenyl, benzyl, tolyl, 4-methyl-2-sulfophenyl,
[3]
3,4-methylenedioxyphenyl, 4-me-. til-3-carboxyphenyl, 4-methyl-2-hydroxymethiophenyl or phenyl substituted at position 4 with methyl, methoxy, aminosulfonyl, acetyl, ethoxycarbonylaminosulfonyl or sulfo group, at position 2 with chlorine, and at position 3 with a nitro group, distinguishing "With the fact that the polyamide cycloalkylSulphonyl succinic acid of General formula (11)
0 «^ <> о в в where А has the indicated value;
B and D are substituents, one of which is a hydroxyl group, and the other is an NH-R group, where R has the indicated meanings, is subjected to dehydration with acetic anhydride in the presence of anhydrous sodium acetate.

类似技术:

---

公开号 | 公开日 | 专利标题

---

EP0200638B1|1989-04-19|Process for the preparation of |-1-phenyl-1-diethyl amino carbonyl 2-amino methyl cyclopropane hydrochloride

---

EP2354118A1|2011-08-10|Process for the preparation of combretastatine

---

SU1165231A3|1985-06-30|Method of obtaining n-substituted 3-cycloalkylsulfonyl-pyrolydion-2,5

---

EP0005689A1|1979-11-28|Lactam-N-acetic acids, their amides, process for their preparation and therapeutic compositions containing them

---

SU1279526A3|1986-12-23|Method of producing derivatives of oximes of pyruvic acid or amides teherof

---

FR2531950A1|1984-02-24|O-AMINO ACID AMIDE DERIVATIVES, THEIR PREPARATION, USE IN THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS AND CARDIOVASCULAR DISORDERS, AND COMPOSITIONS CONTAINING SAME

---

EP0117771B1|1987-11-11|Imino-2 pyrrolidines, process for their preparation and their therapeutical use

---

EP0418933A1|1991-03-27|Derivatives of alcadienes, their preparations and medicinal compositions containing them and intermediates

---

DE1770595C3|1975-02-27|2- | -7-nitro-1,2,3,4-tetrahydroquinoline derivatives and their pharmaceutically acceptable acid addition salts

---

RU2037494C1|1995-06-19|Derivatives of 2-azabicyclo-[2,2,1]-hept-5-ene-2-acetic acid

---

BE779775A|1972-08-24|DERIVATIVES OF UREA, METHOD FOR PREPARING THEM AND THEIR APPLICATIONS

---

EP0074873A1|1983-03-23|Derivatives of 3-phenoxy-3-propanol, their preparation and their therapeutic use

---

JPH07304736A|1995-11-21|Indole derivative

---

US3072636A|1963-01-08|Process for the manufacture of ethyleneimine derivatives

---

US4169097A|1979-09-25|2,3-Dihydro-4H-1-benzopyran-4-one O-carbamoyl oximes

---

EP0220112A2|1987-04-29|Aromatic derivatives substituted by an |-alkanol group with an antimicrobial activity, their preparation and compositions containing them

---

CH624389A5|1981-07-31|Process for the preparation of new methylamine derivatives

---

RU2763728C1|2021-12-30|Application of 3-|-2-oxoethylidene)morpholin-2-one as antimicrobial agent

---

SU770040A1|1992-04-23|Derivatives of benzfurane displaying neurotropic activity of depriming kind

---

CH615171A5|1980-01-15|

---

EP0125975B1|1986-03-26|Diphenylazomethines carrying an esterified chain, their preparation and their therapeutical use

---

FR2653430A1|1991-04-26|NEW DIHYDRO-1,2 OXO-2 QUINOXALINE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC USE

---

EP0279350A2|1988-08-24|Fused azepinone and azocinone derivatives , process for their preparation, agents containing them and their use, as well as their intermediates during their production

---

CH629796A5|1982-05-14|Therapeutically active compounds of 4-|benzoic acid

---

DE3008903A1|1980-09-18|2-MERCAPTOACYLPYRAZOLIDINONE-3-CARBONIC ACID DERIVATIVES

同族专利:

---

公开号 | 公开日

---

ATA368480A|1983-08-15|

---

NO154493B|1986-06-23|

---

JPH0325422B2|1991-04-05|

---

IT1141606B|1986-10-01|

---

GB2054589B|1984-07-25|

---

PL127255B1|1983-10-31|

---

SU1373704A1|1988-02-15|

---

IT8068139D0|1980-07-17|

---

DK159418C|1991-03-18|

---

LU82636A1|1980-10-24|

---

GR69590B|1982-07-05|

---

DK159418B|1990-10-15|

---

CA1135707A|1982-11-16|

---

PL127256B1|1983-10-31|

---

IL60612A|1984-05-31|

---

PL127097B1|1983-09-30|

---

NO154493C|1986-10-01|

---

FI74948B|1987-12-31|

---

JPS5639067A|1981-04-14|

---

YU183080A|1983-09-30|

---

IL60612D0|1980-09-16|

---

DE3026755A1|1981-02-05|

---

CS226015B2|1984-03-19|

---

AT374177B|1984-03-26|

---

FI802268A|1981-01-18|

---

SE450831B|1987-08-03|

---

FR2461700B1|1985-04-26|

---

GB2054589A|1981-02-18|

---

FI74948C|1988-04-11|

---

HU178455B|1982-05-28|

---

AU6048080A|1981-01-15|

---

AU535388B2|1984-03-15|

---

US4364958A|1982-12-21|

---

NO802134L|1981-01-19|

---

NL8004093A|1981-01-20|

---

SE8005208L|1981-01-18|

---

DD152126A5|1981-11-18|

---

FR2461700A1|1981-02-06|

---

PL127257B1|1983-10-31|

---

BE884353A|1980-11-17|

---

ES494310A0|1981-08-01|

---

DD156562A5|1982-09-08|

---

SU1192616A3|1985-11-15|

---

CH651296A5|1985-09-13|

---

ES8106141A1|1981-08-01|

---

SU1156594A3|1985-05-15|

---

SU1007555A3|1983-03-23|

---

PL225695A1|1981-10-30|

---

IN151488B|1983-05-07|

---

DE3026755C2|1991-07-11|

---

DD156572A5|1982-09-08|

---

YU41935B|1988-02-29|

---

DK307580A|1981-01-18|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US3538114A|1966-08-12|1970-11-03|Basf Ag|N--succinimides|

---

GB1319772A|1969-06-18|1973-06-06|Geistlich Soehne Ag|Succinimides|

---

US3804856A|1970-09-04|1974-04-16|Sumitomo Chemical Co|N-phenylsuccinimides|

---

CA950916A|1970-09-04|1974-07-09|Shigehiro Ooba|N-phenylsuccinimide derivatives|

---

JPS4833025A|1971-08-28|1973-05-07|

---

JPS5412904B2|1973-05-18|1979-05-26|DE3637507A1|1986-11-04|1988-05-05|Bayer Ag|NEW METHOD FOR PRODUCING PARTLY NEW 3-SULFENYLMALEINIMIDES AND THEIR USE|

---

DE3719764A1|1987-06-13|1988-12-22|Bayer Ag|ION EXCHANGE RESINS LOADED WITH CHINOLON CARBONIC ACID DERIVATIVES, THEIR PRODUCTION AND USE|

---

US5892057A|1997-09-18|1999-04-06|Pierce Chemical Company|Preparation of sulfo-N-hydroxysuccinimide salts|

---

DE69814110T2|1997-09-18|2004-01-29|Pierce Chemical Co|SULFO-N-HYDROXYSUCCINIMIDES AND METHOD FOR THE PRODUCTION THEREOF|

---

EP1132379A4|1998-09-21|2005-02-16|Takeda Pharmaceutical|Novel thiol derivatives, process for producing the same and utilization thereof|

---

HU226421B1|1998-11-09|2008-12-29|Sanofi Aventis|Process for racemizing optically active 2--2--ethylamino)-acetamides|

法律状态:

优先权:

---

申请号 | 申请日 | 专利标题

---

HU79CI1951A|HU178455B|1979-07-17|1979-07-17|Process for producing new 1-substituted-3-cycloalkyl-sulfonyl-pyrrolidine-2,5-dione derivatives|

---