RU2026282C1 - Method of synthesis of propenoic acid derivatives and their stereoisomers - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: products: derivatives of propenoic acid of the formula (Z-X; A)--C₆H₃-K-C₆H₃-C(COOCH₃)CHOCH₃ where K - oxygen or sulfur; A - hydrogen, halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy, hydroxy, phenoxy or C₁-C₄-alkylcarbonyl. Reagent 1: compound of the formula: (Z-X; A)--C₆H₃-K-C₆H₃-C(COOCH₃)=CH-OR₃ where R₃ - metal atom. Reagent 2: compound of the formula CH₃L where L - splitting off group. Synthesized compounds are used in agriculture. EFFECT: improved method of synthesis. 7 tbl

Description

 The invention relates to derivatives of propanoic acid exhibiting fungicidal activity and to methods for their preparation.

и их стереоизомеров, где А представляет собой атом водорода, галогена, группу С₁-С₄ алкила, С₁-С₄ алкокси, гидрокси, фенокси, или С₁-С₄алкилкарбонила; К представляет собой кислород или серу; Х представляет собой 0, S(0)_n, NH, NR₁, CH₂, CHR₂, CO, CH₂CH₂, CH=CH, OCH₂, (CH₂)_mO, CHR_nO, OCH₂O, S(O)_nCH₂, S(O)CH₂O, NR₁CH₂, COO, OOC, SO₂O, COCH₂O, COCHR₁O, CONH, NHCO, NHSO₂, COS, SCO, N=N, CH₂OCO, CH₂SCO, CH₂NHCO, CH₂ON= CH, OCH₂CH₂O, NR₁N=CH, CH₂OCONH, CH=CHCH₂O, (R₂)₂P + CH₂O^-, N(COR₁), N=CH, CH(OH), CO₂CH₂, SCH₂O, NR₁CO, S(O)₂NH или СONR₁; R₁представляет собой С₁-С₄
алкил; R₂ представляет собой фенил; n равно 0, 1 или 2; m равно 1, 2, 3, 4 или 5; Q представляет собой галогенидный анион; Z представляет собой фенил (необязательно: монозамещенный С₁-С₆алкилом, С₁-С₄ алкокси, С₁-С₄ галоидалкилом, фенокси, фенилом, амином, окси, 1-(С₁-С₄ алкоксикарбонил)-2-(С₁-С₄ алкокси)-винилом, С₁-С₄галоидалкокси или С₁-С₄ алкоксикарбонилом, или моно- или дизамещенный галогеном, нитро, С₁-С₄ алкилом или циано), нафтил, хинолил, пиридинил (необязательно монозамещенный С₁-С₄ алкилом, С₁-С₄ алкоксикарбонилом, амино, галогеном, нитро, С₁-С₄ алкилкарбониламином, ди(С₁-С₄алкилсульфонил)амино или СН(О)NH,моно- или дизамещенный С₁-С₄галоидалкилом или циано, или дизамещенный амином и одним из следующих заместителей: цианом, галогеном или С₁-С₄ алкокси, или дизамещенный нитро и одним из следующих заместителей: циано, галогеном или ди-(С₁-С₄алкил/амином или С₁-С₄ алкокси, или замещенный циано и двумя группами С₁-С₄ алкила/, пиримидин дизамещенный С₁-С₄ алкилом и С₁-С₄ алкилтио, пиримидинил/ необязательно замещенный С₁-С₄ алкилом, С₁-С₄галоидалкилом, С₁-С₄ алкилтио, циано, нитро, фенилом, НО₂С, С₁-С₄алкоксикарбонилом или С₁-С₄ алкилсульфонилом, или моно- или дизамещенный С₁-С₄ алкокси, или моно- или дизамещенный галогеном или тризамещенный галогеном или дизамещенный галогеном и одним из следующих заместителей С₁-С₄ алкилом, или С₁-С₄ алкилтио/, пиразинил /необязательно/ монозамещенный галогеном или циано, или дизамещенный С₁-С₄ алкилом/, пиридазинил /необязательно: монозамещенный С₁-С₄ алкокси, фенилом или аминокарбонилом, или моно- или дизамещенный галогеном, или дизамещенный галогеном и С₁-С₄ алкилом/, бензотиазолил, тиенил/ необязательно: монозамещенный пиразолилом/ замещенным, в свою очередь, С₁-С₄ алкилом и С₁-С₄ галоидалкилом/, или пиридилом в свою очередь необязательно монозамещенным нитрогруппой/, или дизамещенный галогеном/, 1,2,4-триазолил, хиноксалинил/ монозамещенный галогеном/, 1,3,5-триазинил/ дизамещенный галогеном или дизамещенный галогеном и С₁-С₄ алкокси/, тиазолил/ при желании: монозамещенный нитро, или моно- или дизамещенный С₁-С₄ алкилом/, бензоксазолил, пиридинил-N-оксид; тиено /2,3-d/ пиримидинил, пирролил/ необязательно: монозамещенный С₁-С₄/алкилом/, изоксазолил /монозамещенный С₁-С₄ алкилом/, 1,3,4-тиадиазолил, пиразолил /замещенный галогеном и двумя С₁-С₄алкильными группами/, или 1,2,4-триазинил/ монозамещенный фенилом/; при условии, что когда Z является назамещенным фенилом и Х и К оба представляют собой кислород, то А не является водородом, отличающийся тем, что соединения формулы II

в которой R₃ представляет собой атом металла, обрабатывают соединением формулы: СH₃L, в которой L представляет собой отщепляемую группу.In particular, the invention relates to compounds of formula (1) and a method for their preparation, namely, a method for producing propanoic acid derivatives of the general formula I

and stereoisomers thereof, wherein A represents a hydrogen atom, a halogen atom, a C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy, hydroxy, phenoxy, or C ₁ -C ₄ alkylcarbonyl; K represents oxygen or sulfur; X represents 0, S (0) _n , NH, NR ₁ , CH ₂ , CHR ₂ , CO, CH ₂ CH ₂ , CH = CH, OCH ₂ , (CH ₂ ) _m O, CHR _n O, OCH ₂ O , S (O) _n CH ₂ , S (O) CH ₂ O, NR ₁ CH ₂ , COO, OOC, SO ₂ O, COCH ₂ O, COCHR ₁ O, CONH, NHCO, NHSO ₂ , COS, SCO, N = N, CH ₂ OCO, CH ₂ SCO, CH ₂ NHCO, CH ₂ ON = CH, OCH ₂ CH ₂ O, NR ₁ N = CH, CH ₂ OCONH, CH = CHCH ₂ O, (R ₂ ) ₂ P + CH ₂ O ^- , N (COR ₁ ), N = CH, CH (OH), CO ₂ CH ₂ , SCH ₂ O, NR ₁ CO, S (O) ₂ NH or CONR ₁ ; R ₁ represents C ₁ -C ₄
alkyl; R ₂ represents phenyl; n is 0, 1 or 2; m is 1, 2, 3, 4 or 5; Q represents a halide anion; Z represents phenyl (optional: monosubstituted with C ₁ -C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, phenoxy, phenyl, amine, hydroxy, 1- (C ₁ -C ₄ alkoxycarbonyl) -2- (C ₁ -C ₄ alkoxy) vinyl, C ₁ -C ₄ haloalkoxy or C ₁ -C ₄ alkoxycarbonyl, or mono- or disubstituted with halogen, nitro, C ₁ -C ₄ alkyl or cyano), naphthyl, quinolyl, pyridinyl ( optionally monosubstituted C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxycarbonyl, amino, halogen, nitro, C ₁ -C ₄ alkylcarbonylamine, di (C ₁ -C ₄ alkylsulfonyl) amino or CH (O) NH, mono- or disubstituted C ₁ -C ₄ haloalkyl silt and cyano, or disubstituted with an amine and one of the following substituents: cyan, halogen or C ₁ -C ₄ alkoxy, or disubstituted with nitro and one of the following substituents: cyano, halogen or di- (C ₁ -C ₄ alkyl / amine or C ₁ -C ₄ alkoxy, or substituted with cyano and two C ₁ -C ₄ alkyl groups /, pyrimidine disubstituted with C ₁ -C ₄ alkyl and C ₁ -C ₄ alkylthio, pyrimidinyl / optionally substituted with C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ alkylthio, cyano, nitro, phenyl, HO ₂ C, C ₁ -C ₄ alkoxycarbonyl or C ₁ -C ₄ alkylsulfonyl, or mono- or disubstituted C ₁ -C ₄ alkoxy, or mono- or disubstituted by halogen or trisubstituted by halogen or disubstituted by halogen and one of the following substituents: C ₁ -C ₄ alkyl, or C ₁ -C ₄ alkylthio /, pyrazinyl / optionally / monosubstituted with halogen or cyano, or disubstituted with C ₁ -C ₄ alkyl /, pyridazinyl / optionally: monosubstituted With ₁ -C ₄ alkoxy, phenyl or aminocarbonyl, or mono- or disubstituted with halogen, or disubstituted with halogen and C ₁ -C ₄ alkyl /, benzothiazolyl, thienyl / optionally: monosubstituted with pyrazolyl / substituted in turn, C ₁ -C ₄ alkyl and C ₁ -C ₄ haloalkyl / or pyridyl, in turn, optionally monosubstituted by nitro group /, or disubstituted by halogen /, 1,2,4-triazolyl, quinoxalinyl / monosubstituted by halogen /, 1,3,5-triazinyl / disubstituted by halogen or disubstituted by halogen and C ₁ -C ₄ alkoxy /, thiazolyl / optionally: monosubstituted nitro, or mono- or disubstituted With ₁ -C ₄ alkyl /, benzoxazolyl, pyridinyl-N-oxide; thieno / 2,3-d / pyrimidinyl, pyrrolyl / optionally: monosubstituted With ₁ -C ₄ / alkyl /, isoxazolyl / monosubstituted With ₁ -C ₄ alkyl /, 1,3,4-thiadiazolyl, pyrazolyl / substituted with halogen and two C ₁ -C ₄ alkyl groups /, or 1,2,4-triazinyl / monosubstituted with phenyl /; with the proviso that when Z is substituted phenyl and X and K are both oxygen, A is not hydrogen, characterized in that the compounds of formula II

in which R ₃ represents a metal atom, treated with a compound of the formula: CH ₃ L, in which L represents a leaving group.

 The compounds of formula I are active fungicides for controlling a wide range of pathogens in various plant species.

 The compounds of formula (I) are safer with respect to cultivated plants (e.g. grapes) compared to known compounds with similar structure.

 The compounds are also useful as industrial (as opposed to agricultural) fungicides, for example, for the prevention of fungal infections of wood, leather, leather products and especially paint films.

 The compounds can be used as fungicides, usually using a carrier or diluent (composition).

 When used as fungicides, the compounds can be applied in a variety of ways. For example, they can be applied in the form of a composition and as such directly on the foliage of plants, seeds or the habitat of plants or growing plants, or can be applied in the form of spraying, dust, cream or paste, in the form of vapors or granules of slow action. Any part of the plant can be treated, including foliage, trunk, branches or roots or the earth around the roots, or seeds before sowing, or the soil as a whole, as well as irrigation water or hydroponic plant growing systems.

The invention is illustrated by the following examples. In all examples, the term "ether" refers to diethyl ether, magnesium sulfate is used to dry the solutions, and the solutions are concentrated under reduced pressure. Reactions involving moisture-sensitive intermediates are carried out in a nitrogen atmosphere, and the solvents are dried before use, if necessary. Unless otherwise indicated, chromatography is carried out on a column filled with silica gel. Where indicated, infrared and NMR spectroscopy data are selective without specifying all absorption bands in all cases. ¹ H-NMR spectra were recorded using CDCl ₃ as solvent, unless otherwise indicated. The following abbreviations are used everywhere:
DME - dimethoxyethane, THF - tetrahydrofuran, DMF - N, N-dimethylformamide, NMR - nuclear magnetic resonance, IR - infrared, s - singlet, d - doublet, t - triplet, m - multiplet, mp - melting point,
GC = gas chromatography,
TLC = thin layer chromatography,
HPLC = high performance liquid chromatography,
Vg = wide (band),
ppm = parts per million (ppm).

Example 1. This example illustrates the preparation of (E) -methyl-2- [2- (3- [3-methoxyphenoxy] phenoxy) phenyl] -3-methoxypropenoate (compound 129 of the table, 1) ,
To a stirred solution of 0.61 g of sodium in 10 ml of methanol, 4.34 g of resorcinol is added in one portion. After the resulting mixture was stirred for half an hour at room temperature, the excess methanol was distilled off under reduced pressure. To the residue, in the form of an oily orange liquid, 6.6 ml of pyridine, 14.74 g of 3-bromoanisole and 192 mg of copper chloride are added. The mixture was stirred for 66 hours at 125 ° ^C, then cooled and poured into dilute hydrochloric acid, and then cooled and poured into dilute hydrochloric acid, and then subjected to extraction with ether.

The ether extracts are back-extracted with a dilute aqueous sodium hydroxide solution. The aqueous extracts are acidified with dilute hydrochloric acid and extracted with ether. The resulting ether extracts are washed successively with water and brine, and then dried and concentrated, resulting in 3.72 g of a red oily liquid. After distillation of this liquid (oven temperature 170 ^C, pressure 0.05 mmHg) gave 1.71 g of 3- (3-methoxyphenoxy) phenol as an oil pale yellow.

¹ H NMR delta: 3.78 (3H, s), 4.93 (1H, s) ppm.

To a stirred solution of 0.18 g of sodium in 4 ml of methanol, 1.70 g of 3- (3-methoxyphenoxy) phenol is added in one portion. After the resulting mixture was stirred for half an hour at room temperature, the excess methanol was distilled off under reduced pressure. To the residue, as an oil of orange color is added 0.85 g of o-bromophenylacetic acid and 40 mg of copper chloride and the reaction mixture was stirred for one hour at 130 ° ^C. Thereafter, thereto was further added 0.4 g of o-bromophenylacetic acid and 0 13 g of sodium ethoxide was added and stirring continued at 130 ^{° C} for a further 3 hours. The mixture was then cooled, acidified with dilute hydrochloric acid and subjected to extraction with ether.

The ether extracts are washed successively with water and brine, then dried and concentrated, to give 3.12 g of a red oily liquid containing 2- [3- (3-methoxyphenoxy) phenoxy] phenylacetic acid. To 3.12 g of this crude acid was added 40 ml of methanol and 3 drops of concentrated sulfuric acid. The reaction mixture was stirred for one hour at ⁹⁰ ° C, then slowly cooled, poured into water and subjected to extraction with ether. The ether extracts are washed successively with a dilute aqueous solution of sodium hydroxide, water and brine, dried and concentrated, yielding 1.33 g of a yellow oily liquid. After distilling it (bath temperature 160 ^C, pressure 0.07 mmHg) afforded 1.03 g (yield 36% based on 3- (3-methoxyphenoxy) phenol), 2- [3- (3- methoxyphenoxy) phenoxy] phenyl acetate.

¹ H NMR delta: 3.62 (1H, s), 3.68 (2H, s), 3.78 (3H, s), ppm.

A mixture of 1.00 g of methyl- [3- (3-methoxyphenoxy) phenoxy] phenylacetate and 3.34 ml of methyl formate in 1 ml of DMF is added dropwise over 10 minutes to a stirred suspension of 0.13 g of sodium hydride in 10 ml of DMF, cooled ice to a temperature below 10 ^{° C} (with effervescence occurs). After complete addition, the reaction mixture was stirred for 2 hours at room temperature, then poured into water, acidified with dilute hydrochloric acid and extracted with ether. The extracts are washed with water, dried and concentrated, resulting in 1.09 g of a yellow oily liquid. 0.76 g of potassium carbonate and 0.33 g of dimethyl sulfate are added to a stirred solution of this liquid in 20 ml of DMF, and the resulting mixture is stirred at room temperature for 2.5 hours, then it is poured into water and subjected to extraction with ether.

 The extracts are washed with water, dried, concentrated and chromatographed using a 1: 1 mixture of ether and gasoline as eluent. The result is 0.61 g (55% yield based on methyl 2- [3-methoxyphenoxy) phenoxy] phenyl acetate) of the target compound as a colorless viscous oily liquid.

¹ H NMR delta: 3.60 (3H, s), 3.75 (3H, s), 3.78 (3H, s), 6.55-6.72 (5H, m), 6.97 (1H d) 7.10-7.30 (6G, m), 7.48 (1H, s) ppm. IR max (nujol) 1713, 1628 cm ^-1 .

 Example 2. This example describes the preparation of (E) -methyl-3-methoxy-2- [2- (3-phenoxyphenylthio) phenyl [propenoate (compound N 446 from table 3).

2-меркаптофенилуксусную кислоту получают описанным в литературе способом (см. D.Papa и др., J.Org. Chem., 1949, 24, 723,, R.H.Glauert, F.G.Mann, J. Chem. Soc., 1952, 2127 и ссылки в этой статье). 1,68 г 2-меркаптофенилуксусной кислоты добавляют к перемешиваемому раствору 0,8 г гидроксида натрия в 10 мл метанола (в сравнении с D.С.Atkinson и др., J.Mеd. Chem., 1983, 26, 1361). Образующийся оранжевый раствор перемешивают при комнатной температуре в течение 90 мин, затем концентрируют при пониженном давлении, удаляя остатки ментола путем азеотропной перегонки с толуолом. В результате получают желтое твердое вещество.

2-mercaptophenyl acetic acid is prepared as described in the literature (see D. Papa et al., J. Org. Chem., 1949, 24, 723 ,, RHGlauert, FGMann, J. Chem. Soc., 1952, 2127 and references in this article). 1.68 g of 2-mercaptophenylacetic acid is added to a stirred solution of 0.8 g of sodium hydroxide in 10 ml of methanol (compared to D. C. Atkinson et al., J. Med. Chem., 1983, 26, 1361). The resulting orange solution was stirred at room temperature for 90 minutes, then concentrated under reduced pressure, removing menthol residues by azeotropic distillation with toluene. The result is a yellow solid.

To a stirred solution of this yellow substance in 20 ml of DMF was added 0.2 g of copper chloride and a solution of 2.49 g of 3-phenoxybromobenzene obtained from 3-phenoxyphenol and triphenylphosphine dibromide according to the method described by JPSchaefer et al., Org. Synth., Coll. v. 5, 142) in 10 ml of DMF. The resulting mixture was heated at 95 ^{° C} for 1 3/4 hours at ¹²⁵ ° C for 2 hours and then at reflux temperature for a further 2 hours. After cooling, the reaction mixture was poured into aqueous sodium hydroxide solution and washed three times with ether. The aqueous solution was acidified with concentrated hydrochloric acid and subjected to extraction with ether three times.

 The extracts are washed with water, dried and concentrated, resulting in 2.2 g of an oily purple liquid, consisting mainly of 2- (3-phenoxyphenylthio) phenylacetic acid. A solution of this oily liquid in 20 ml of methanol was added to acidic methanol obtained by careful processing of 30 ml of methanol with 3.5 ml of acetyl chloride, and the resulting mixture was stirred for 90 minutes at room temperature. The reaction mixture was then concentrated and the residue was partitioned between ether and aqueous sodium bicarbonate. The organic layer was separated and washed successively with an aqueous solution of sodium hydroxide (twice) and three times with water, then dried and concentrated, resulting in 2.06 g of crude 2- (3-phenoxyphenylthio) phenylacetate as a purple oily liquid.

IR max (film): 1740 cm ^-1 , purity 94% (determined by gas chromatography). The crude methyl 2- (3-phenoxyphenylthio) phenylacetate was converted to the target compound in 53% yield in two steps, in the same manner as described in Example 1 for the conversion of methyl 2- [3- (3-methoxyphenoxy) phenoxy] phenylacetate in (E) -methyl-2- [2- (3-methoxyphenoxy] phenoxy) phenyl] -3-methoxypropenoate, namely by formylation with methyl formate and sodium hydride and subsequent o-methylation with dimethyl sulfate and potassium carbonate. The resulting product is an orange resin (purity determined by gas chromatography, 98%), which crystallized upon standing. T.plav. 48-51.5 ^about S.

IR max (film): 1710 and 1632 cm ^-1 .

¹ H NMR (270 MHz): Delta 3.62 (3H, s), 3.73 (3H, s), 6.78 (1H, dd), 6.88-7.00 (4H, m), 7 05-7.36 (7H, m), 7.42 (1H, d), 7.48 (1H, s) ppm.

 Example 3. This example illustrates the preparation of (E) -methyl-3-methoxy-2- (2- [3-benzoylphenoxy] phenyl) propenoate (compound 12 of Table 1).

 10.0 g of methyl 2- (3-hydroxymethylphenoxy) phenylacetate, 10 g of celite are stirred in 100 ml of methylene chloride and 15.85 g of pyridinium chlorochromate is added to the mixture in one go. After the mixture was stirred at room temperature for 2.5 hours, it was filtered and the filtrate was evaporated, yielding 8.48 g of methyl 2- (3-formylphenoxy) phenylacetate as an orange oily liquid that was pure enough to be pure could be used without further purification.

IR max (film): 1740, 1700 cm ^-1 .

¹ H NMR (270 MHz) delta: 3.59 (3H, s), 3.69 (2H, s), 6.92 (1H, d), 7.14-7.20 (1H, t), 7 , 23-7.37 (3H, m), 7.43 (1H, m), 7.50 (1H, t), 7.60 (1H, dd), 9.95 (1H, s) ppm .

To 2.30 g of the cooled stirred solution of the aldehyde obtained in the previous step in THF was added dropwise phenyl magnesium bromide (2.84 m 3 M solution in ether) at such a rate that the temperature did not rise above -30 ^C. After complete addition (35 min) the reaction mixture is slowly warmed to room temperature, stirred overnight and then cooled in an ice bath, carefully adding water. After that, dilute hydrochloric acid was added to it and subjected to extraction with ethyl acetate. The extracts are dried and evaporated, resulting in a yellow oily liquid, which is purified using flash chromatography using a mixture of hexane and ethyl acetate taken in a 2: 1 ratio as eluent. The result of 1.69 g of 2 - [(3-alpha-hydroxy) benzyl) -phenoxy] phenylacetate in the form of a pale yellow oily liquid.

¹ H NMR (270 MHz) delta: 3.57 (3H, s), 3.68 (2H, s), 5.79 (1H, s), 6.79-6.90 (2H, m), 7 05-7.13 (3H, m); 7.18-7.40 (9H, m) ppm.

 0.91 g of the hydroxyether obtained in the previous step are stirred at room temperature in 25 ml of methylene chloride with the addition of two celite spatulas. Then, 0.65 g of pyridinium chlorochromate was added to the mixture and it was stirred for 3 hours, then it was filtered, the filtrate was evaporated and purified using high-performance liquid chromatography using a mixture of hexane and ethyl acetate taken in a 3: 1 ratio as eluent. The result is 0.56 g of methyl 2- (3-benzoylphenoxy) phenylacetate as a pale yellow gum.

¹ H NMR (270 MHz) delta: 3.60 (3H, s), 3.70 (2H, s), 6.93 (1H, d), 7.10-7.63 (10H, m), 7 81 (2H, d) ppm.

IR max (film): 1740, 1660 cm ^-1.
The resulting product is transferred to the target compound by treatment with sodium hydride and methyl formate, followed by the addition of potassium carbonate and dimethyl sulfate. The treatment is carried out in two stages, as described in example 1 for a similar transformation.

IR max (film): 1710, 1660, 1635 cm ^-1 .

¹ H NMR (270 MHz) delta: 3.60 (3H, s), 3.75 (3H, s), 6.98 (1H, d), 7.12-7.20 (2H, m), 7 26-7.52 (8H, m), 7.47 (1H, s), 7.55-7.63 (1H, m), 7.80 (2H, dd) ppm.

 Example 4. This example illustrates the preparation of (E) -methyl-3-methoxy-2- (2- [3-benzylphenoxy] phenyl) propenoate (compound N 9 from table 1).

To 1.68 g of methyl 2 - [(3 (Malfa-oxy) benzyl) phenoxy] phenylacetate, prepared as described in Example 3, the method was added dropwise at ⁵ ° C and stirring, 3.28 grams of trifluoroacetic acid. After the addition is complete, 2.24 g of triethylsilane is slowly added dropwise to the resulting mixture. The resulting clear solution was stirred overnight, diluted with water and subjected to extraction with ether. The ether fraction was washed with an aqueous solution of sodium bicarbonate, dried, concentrated and purified using high-performance liquid chromatography using a 4: 1 mixture of hexane and ether as eluent. The result is 1.03 g of methyl -2 (3-benzylphenoxy) phenylacetate as a colorless oily liquid.

IR max (film): 1742 cm ^-1 .

 The resulting product is transferred to the target compound by treatment with sodium hydride and methyl formate and then adding potassium carbonate and dimethyl sulfate. The treatment is carried out in two stages, as described for a similar transformation in example 1.

IR max (film): 1708, 1635 cm ^-1 .

¹ H NMR (270 MHz) delta: 3.56 (3H, s), 3.72 (3H, s), 3.93 (2H, s), 6.76-6.93 (4H, m), 7 08-7.31 (10H, m); 7.47 (1H, s) ppm.

 The following compounds are listed in table. 1-4 are obtained by the method described in examples 1-4. Everywhere in Tables 1-4, the methyl-3-methoxypropenoate group has an (E) configuration.

 Tab. 3 includes compounds of the above formula. For the first four compounds, all values of X, D, G, A, B, and E are shown in Table 1. Those. Compounds NN 13-66 are the same, with the exception of the K value, to which oxygen corresponds in Table 1, and in Table 1. 3 - sulfur. Compound N325 corresponds to the above formula, where X is oxygen and A, B, D, E and G are all hydrogen. A description of the preparation of compound 325 is given in Example 2.

Табл. 4 включает соединения вышеприведенной общей формулы, где все значения Z, X, A, B и E указаны в табл.2, т.е. соединения 1-320 те же, что и в табл. 2, за исключением значения К, которому в табл.2 соответствует кислород, а в табл.4 - сера.

Tab. 4 includes compounds of the above general formula, wherein all values of Z, X, A, B, and E are shown in Table 2, i.e. compounds 1-320 are the same as in table. 2, with the exception of the K value, to which oxygen corresponds in Table 2, and sulfur in Table 4.

In the table. 5 shows the data of proton NMR for a number of compounds of the table. 1, 2, 3 and 4. The chemical shifts in ppm refer ^-1 from tetramethylsilane, in all cases in deuterated chloroform is used as solvent. The column entitled “frequency” refers to the operating frequencies in NMR spectrometers. The following abbreviations are used in Table 5: Ush - widened band, s - singlet, d - doublet, t - triplet, k - quartet, m - multiplet.

 Test Example The proposed compounds are tested in relation to various fungal diseases of plant leaves. The tests are carried out as follows.

 Plants are grown in John Innes Potting Compost (N 1 or 2) in pots with a diameter of 4 cm. Preparations of the test compounds are prepared either by grinding in a ball mill with water dispersol T, or by dissolving in acetone or a mixture of acetone and ethanol and then diluting to the desired concentration immediately before use. In the case of leaf diseases, the compositions (the concentration of the active component, if not specified, 100 ppm) are sprayed with leaves or they are introduced into the soil. When spraying, the composition is applied in the maximum amount retained on the leaves. When introduced into the soil to the root system, the final concentration corresponds to about 40 ppm. active component calculated on dry soil. When processing cereals, Tween 20 is added to the compositions in such an amount that its final concentration is 0.05%.

 In most cases, the test compound is applied to the soil or leaves are sprayed with it one or two days before the infection of the plant with the pathogen.

 The exceptions are experiments in Erysiphe graminis. In this case, the plants are infected 24 hours before treatment. Infection with leaf pathogens is carried out by spraying the leaves of test plants with spore suspensions.

 After infection, the plants are kept under conditions favorable for the development of the disease, until its obvious signs appear, by which an assessment of the degree of its development can be made. The time between the moment of infection and the assessment of the degree of development of the disease, vary up to 4 to 14 days depending on the disease and environmental conditions.

 The degree of development of the disease is evaluated in points according to the following system: 4 = absence of disease, 3 = disease from traces to 5% from untreated plants, 2 = disease 6-25% from untreated plants, 1 = disease 26-59% from untreated plants, 0 = disease 60-100% of untreated plants.

 The results are shown in table.6.

 Since the compounds that meet this application have a wide range of activity, the applicants compared them with mancozeb, which is one of the most broad-spectrum fungicides available from the industry. As for structural similarity, carboxin and pyroxyfur, as well as the compound ap 01788261 are proposed for comparison. The biological data of mancozeb, carboxin and pyroxyfur are given in Table 7 below. A biological test to obtain this data is carried out using the method described in Test Example 1.

 Thus, from the above data, the useful properties of the compounds of this invention and their advantages both over the most active commercial fungicides and in comparison with the closest analogue in structure are clear.

 p. 54

Claims (1)

 METHOD FOR PRODUCING PROPENIC ACID DERIVATIVES AND THEIR STEREOISOMERS. A method of obtaining derivatives of propenic acid of the General formula

where A is hydrogen, halogen, a C ₁ -C ₄ -alkyl group, C ₁ -C ₄ -alkoxy, hydroxy, phenoxy, or C ₁ -C ₄ alkylcarbonyl;
K is oxygen or sulfur;
X is O, S (O) _n , NH, NR ₁ , CH ₂ , CHR ₂ , CO, CH ₂ CH ₂ , CH = CH, OCH ₂ , (CH ₂ ) _m O, CHR ₁ O, OCH ₂ O, S (O) _n CH ₂ , S (O) CH ₂ O, NR ₁ CH ₂ , COO, OOC, SO ₂ O, COCH ₂ O, COCHR ₁ O, CONH, NHCO, NHSO ₂ , COS, SCO, N = N, CN ₂ OCO, CH ₂ SCO, CH ₂ NHCO, CH ₂ ON = CH, OCH ₂ CH ₂ O, NR _1, N = CH, CH ₂ OCONH, CH = CHCH ₂ O, (R _2/2 P ^+, CH ₂ Q ^- , N (COR ₁ ), N = CH, CH (OH), CO ₂ CH ₂ , SCH ₂ O, NR ₁ CO, S (O) ₂ NH or CONR ₁ ;
R ₁ - C ₁ - C ₄ -alkyl;
R ₂ is phenyl;
n is 0, 1 or 2;
m = 1 - 5 is an integer;
Q is a halide anion;
Z is phenyl (optionally monosubstituted With ₁ - C ₆ -alkyl, C ₁ - C ₄ -alkoxy, C ₁ - C ₄ -haloalkyl, phenoxy, phenyl, amine, hydroxy, 1- (C ₁ - C ₄ -alkoxycarbonyl) - 2- (C ₁ - C ₄ alkoxy) vinyl, C ₁ - C ₄ haloalkoxy or C ₁ - C ₄ alkoxycarbonyl or mono or disubstituted with halogen, nitro, C ₁ - C ₄ alkyl or cyano), naphthyl, quinolyl, pyridinyl (optionally monosubstituted C ₁ - C ₄ -alkyl, C ₁ - C ₄ -alkoxycarbonyl, amino, halogen, nitro, C ₁ - C ₄ -alkylcarbonylamine, di (C ₁ - C ₄ -alkylsulfonyl) amino or CH (O) NH, or mono- or disubstituted by C ₁ - C ₄ -galoidalkilom or q ano or disubstituted amine and one of the following substituents: cyano, halogen or C ₁ - C ₄ alkoxy and nitro, or disubstituted by one of the following substituents: cyano, halogen or di (C ₁ - C ₄ alkyl) amino, or C ₁ - C ₄ alkoxy, or substituted with cyano and two C ₁ - C ₄ alkyl groups), pyrimidine disubstituted with C ₁ - C ₄ alkyl and C ₁ - C ₄ alkylthio, pyrimidinyl (optionally substituted C ₁ - C _4- alkyl, C ₁ - C ₄ -haloalkyl, C ₁ - C ₄ -alkylthio, cyano, nitro, phenyl, HO ₂ C, C ₁ - C ₄ -alkoxycarbonyl or C ₁ - C ₄ -alkylsulfonyl, or mono- or di-C ₁ - ₄ alkoxy, or mono- or disubstituted by halogen or trisubstituted by halogen, or disubstituted with halogen and one of the following substituents: C ₁ - C ₄ alkyl or C ₁ - C ₄ alkylthio), pyrazinyl (not necessarily monosubstituted by halogen or cyano, or disubstituted C ₁ - C ₄ -alkyl), pyridazinyl (not necessarily monosubstituted C ₁ - C ₄ -alkoxy, phenyl or aminocarbonyl, or mono- or disubstituted with halogen or disubstituted with halogen and C ₁ - C ₄ -alkyl), benzothiazolyl, thienyl (not Mandatory monosubstituted pyrazolyl, substituted C ₁ - C ₄ alkyl and C ₁ - ₄ -galoidalkilom or pyridyl, in turn, not necessarily monosubstituted by nitro, or disubstituted by halogen), 1,2,4-triazolyl, quinoxalinyl (monosubstituted by halogen), 1,3,5-triazinyl (disubstituted by halogen or disubstituted by halogen and C ₁ - C ₄ -alkoxy), thiazolyl (optionally monosubstituted nitro, or mono- or disubstituted C ₁ - C ₄ -alkyl), benzoxazolyl, pyridinyl-N-oxide, thieno (2,3-d) -pyrimidinyl, pyrrolyl (not necessarily monosubstituted With ₁ - With ₄ -alkyl), isoxazolyl (monosubstituted With ₁ - With ₄ -alkyl), 1,3,4-thiadiazolyl, pyrazolyl (substituted by halogen and two C ₁ - C ₄ -alkyl groups) or 1,2,4-triazinyl (monosubstituted with phenyl), provided that when Z is unsubstituted phenyl and X and K are both oxygen, then A is not hydrogen,
and their stereoisomers, characterized in that the compounds of General formula

where R ₃ is metal,
treating a compound of the general formula
CH ₃ L,
where L is a leaving group. Priority by signs:
01/22/88 at A - hydroxy, phenoxy, C ₁ - C ₄ -alkylcarbonyl; X is CH (C ₆ H ₅ ), C (= O) CH ₂ O, CH (OH), CO ₂ CH ₂ , COCH (C ₁ - C ₄ -alkyl) -O-S - CH ₂ O; K is oxygen; Z is unsubstituted phenyl or substituted with halogen;
03/17/88 at K - sulfur; X is oxygen, A is hydrogen, Z is phenylpyrimidinyl;
06/21/88 at A - hydrogen; X is Ph ₂ P ⁺ CH ₂ Br ^- , CH ₂ OCO, CH ₂ NCO, CH ₂ SCO, K is oxygen, Z is phenyl;
09/08/88 at A - hydrogen, X - OCH ₂ -; S (O) CH ₂ O, CH ₂ ON = CH, (CH ₂ ) ₃ O, (CH ₂ ) ₅ O, OCH ₂ CH ₂ O, CH ₂ OCONH, K is oxygen, Z is phenyl;
09/15/87 - the remaining values of the radicals A, Z, X, K indicated in the claims.

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