Methods of obtaining intermediates

 

(57) Abstract:

This invention relates to new methods for producing compounds of formula (I)

where one of the groups R1and R2is cyclopropyl and the other is phenyl substituted by two or three groups, which may be the same or different, selected from halogen, nitro, cyano, -(CR4R5)S(O)pR6, -S(O)pR6C1-6alkoxy, C1-4haloalkoxy,1-4of alkyl, C1-4haloalkyl and SF5; where p is 0, 1 or 2; R4and R5independently are hydrogen or C1-4by alkyl; and R6is1-4the alkyl. The method involves the hydrolysis and decarboxylation of compounds of formula (II):

where R1and R2defined above and R3is1-4the alkyl, in the presence of water. When this compound of formula (II) is obtained by acylation of compounds of formula (III):

where R1and R3defined above with compound of formula (IV): R2C(=O)X (IV) wherein R2defined above, X is a leaving group, and the method is carried out in the presence of a magnesium halide and a base. The compound of formula (III), where R' is cyclopropyl, Paul who is a substituted or unsubstituted imidazol-1-ilen ring, with the compound of the formula (VI):

where R3defined above, via the decarboxylation of compounds of formula (VII):

where R1is cyclopropyl and R3defined above. 4 C. and 15 C.p. f-crystals.

This invention relates to new methods of producing intermediate compounds (particularly compounds of beta-keeeper and 1,3-dione), used in the manufacture of pesticides.

Pesticide 4-benzoimidazole, especially herbicides based on 5-cyclopropylethanol and intermediate compounds for their synthesis are described in the literature, for example in the publication of applications at the European patent№ 0418175, 0487353, 0527036, 0560482, 0609798 and 0682659.

There are various ways to obtain these compounds. This invention is an improved or more economical ways of getting pesticides and intermediates used for their production.

This invention, accordingly, provides a method (A) obtain the compounds of formula (I):

where one of the groups R1and R2are cyclopropyl and the other is phenyl substituted by two or three groups, which may be the same or different, selected/SUB>haloalkoxy,1-4of alkyl, C1-4haloalkyl, 1,2,4-triazole-1-yl-SF5; where p is 0, 1 or 2; R4and R5independently are hydrogen or C1-4by alkyl; and R6is1-4by alkyl; where the method involves hydrolysis and decarboxylation of compounds of formula (II):

where R1and R2defined above and R3is1-4the alkyl.

Certain compounds of formula (I) are known, and several methods for their preparation and transformation in herbicide derivatives of 4-benzoimidazole described in applications for European patents listed above.

In formulas (I) and (II) in the formulas below, the preferred meanings of the radicals are as follows.

Preferably the group R1or R2which is substituted by phenyl substituted by two or three groups selected from halogen, trifloromethyl, nitro, -CH2S(O)pCH3, -S(O)pCH3, methoxy, methyl and 1,2,4-triazole-1-yl.

More preferably the group R1or R2which is substituted by phenyl, has as one of the Vice 2-S(O)pCH3group.

More preferably, the GRU-CF3; 2-S(O)pCH3-3-OCH3-4-F; 2-CH2S(O)pCH3-4-VG; 2-(1,2,4-triazole-1-yl)-4-CF32-NO2-4-S(OH)pCH3substituted phenyl.

Most preferably the group R1or R2which is substituted by phenyl, choose from:

2-S(O)pCH3-4-CF3and 2-S(O)pCH3-3-OCH3-4-F substituted phenyl.

Preferably R3is stands or ethyl.

Obtaining compounds of formula (I) from compounds of formula (II) can be carried out in a polar or non-polar solvent (preferably polar solvents). The preferred solvent miscible with water. Examples of polar solvents include NITRILES, especially acetonitrile; dimethyl sulfoxide, dimethylformamide; N,N-dimethylacetamide; N-organic; and ethers, especially dioxane and tetrahydrofuran. Acetonitrile is the preferred solvent for the method (A). Examples of nonpolar solvents include aromatic or aliphatic hydrocarbons, such as toluene and xylene; or an aromatic or aliphatic halogenated hydrocarbons such as chlorobenzene. Usually requires the presence in the environment of the solvent water. Kolichestvo co-solvent. The ratio of solvent/water preferably ranges from about 99.9:0.1 to about 9:1 (by volume).

The most commonly used reaction temperature is from 0°C to the boiling point of the solvent, preferably from 20°C to 120°C and more preferably from 60°C. to 100°C.

Typically the reaction is carried out in the presence of a strong acid, usually a mineral acid, for example sulfuric acid or preferably hydrochloric acid, or organic carboxylic acids, such as triperoxonane acid. The amount of acid present can vary from a catalytic amount to a large excess. Typically, a catalytic amount give good results.

When carrying out the reaction using acidic conditions and readily available reagents, the compounds of formula (I) can be obtained easily, with a large output and with minimal formation of by-products. The reaction is particularly suitable for esters of lower Akilov formula (II), especially those in which R3is stands or ethyl, because these compounds can be obtained from more readily available or less expensive raw materials.

Another object of this invention is the method (C) p is>the de R1and R3such as defined above, with a compound of formula (IV):

R2C(=O)X (IV)

where R2defined above, and X is a leaving group, typically a halogen atom (preferably chlorine); or imida-Zol-1-yl.

In formulas (III) and (IV) the above values of R1and R2such as defined above for formulas (I) and (II).

In a particularly preferred variant of the method (B) the group R1is cyclopropyl; R2is 2-S(O)pCH3-4-CF3or 2-S(OH)pCH3-3-OCH3-4-F substituted phenyl; and R3is stands, ethyl or tert-bootrom.

The compounds of formula R2C(=O)X and their predecessors carboxylic acid, where R2is cyclopropyl, generally described in the literature, and if R2is substituted by phenyl, receive them, in General, are described in applications for European patents listed above, and related publications.

Obtaining compounds of formula (II) from compounds of formulas (III) and (IV) can be carried out by (a) the interaction of enolate metal compounds of the formula (III) with allermuir agent (IV). Enolate metal is preferably magnesium enolate, and receive it, usually in situ, the tion. If you use a magnesium alkoxide, it is usually taken in equimolar amounts.

The interaction of compounds of the formula (III) and (IV) can also be (b) in the presence of a magnesium halide and a base. The magnesium halide is usually the chloride, bromide or iodide magnesium (magnesium iodide conveniently obtain the in situ using magnesium chloride and alkali metal iodide, preferably sodium iodide or potassium iodide).

Used the base can be selected from trialkylamines, such as triethylamine, and pyridine. The amount of magnesium halide is generally 1 equivalent, and the amount used of the base is usually from 1 to 2 equivalents, preferably 2 equivalents. The reaction temperature is usually from 0°C to 100°C, preferably from 0°C. to 30°C.

If the above reaction is carried out using enolate magnesium, may be a side reaction in which the compound (IV) reacts with the alkoxide, which is present as part of a complex enolate magnesium (which is when it is used as a solvent may be present even after removing all alcohol), with complex alcohol ester compounds (IV). Although usually I'm not the author and lead to a reduction of the yield of compound (II). This problem can essentially be avoided if you stick to the techniques with the use of magnesium halide/reasons described above.

Solvents suitable for the above method of obtaining compounds of formula (II) include NITRILES, preferably acetonitrile; aromatic hydrocarbons, preferably toluene; chlorinated hydrocarbons such as dichloromethane; chlorinated aromatic solvents such as chlorobenzene; and ethers such as tetrahydrofuran and 1,4-dioxane.

The compounds of formula (II), where R3is C1-3the alkyl, are novel and, as such, are another object of the present invention.

Another object of this invention is the method (S) for obtaining compounds of formula (III) interaction of the compounds of formula (V):

where R1defined above, and Y is a leaving group, such as cyano or preferably optionally substituted imidazol-1-ilen ring; with the compound of the formula (VI):

where R3defined above; receiving, via the decarboxylation of the intermediate compounds of formula (VII):

where R1and R3defined above, the compounds forstie acid.

In formulas (V), (VI) and (VII) above preferred values of R1such as defined for formulas (I) and (II).

Imidazol-1-ilen group Y is optionally substituted from 1 to 3 (usually one or two) groups selected from C1-4of alkyl, C1-4haloalkyl and halogen. Preferably Y is imidazol-1-yl.

More preferably R1is cyclopropyl; or choose from:

2-S(O)pCH3-4-CF3-phenyl and 2-S(OH)pCH3-3-OCH3-4-F-phenyl.

Most preferably, R1is cyclopropyl.

Preferably R3is stands, ethyl or tert-bootrom.

Obtaining compounds of formula (VII) compounds of the formula (V) or (VI) may be carried out by (a) the interaction of complex metal compounds of the formula (VI) with the compound of the formula (V). The reaction is usually carried out under the conditions described above for the reaction of compounds of formulas (III) and (IV).

The interaction of compounds of the formula (V) and (VI) can also be carried out (b) in the presence of a magnesium halide and a base, usually in the conditions described above for the reaction of compounds of formulas (III) and (IV).

Solvents suitable for the above sposob).

Particularly preferred solvents for the method (S) are acetonitrile and tetrahydrofuran.

Optional compound of formula (V) can be obtained in situ by the interaction of the compounds of formula:

R1C(=O)Cl (VIII)

with 1H-imidazole, optionally substituted from 1 to 3 (usually one or two) groups selected from C1-4of alkyl, C1-4haloalkyl and halogen. Preferably 1H-imidazol unsubstituted. Usually in the reaction using 2 equivalent optionally substituted 1H-imidazole, and the reaction is carried out in an inert solvent, for example acetonitrile or tetrahydrofuran, at temperatures from -20°C to 60°N

The alternate connection of the formula (V) can be obtained in situ by the interaction of the compounds of formula:

R1C(=O)OH (VIIIa)

with optional substituted derivatives of 1,1'-carbonyldiimidazole (preferably 1,1'-carbonyl diimidazol).

Typically used equimolar amount of compounds (V):(VI).

Intermediate compounds of formula (VII), which are betametasone, decarboxylases, usually in situ, in the presence of a strong acid, usually a mineral acid, preferably hydrochloric acid, and usually when temprary (III) are particularly useful for producing compounds in which R1is cyclopropyl, and is more convenient than other known methods, for example methods involving the acylation expensive acid Melodrama (2,2-dimethyl-1,1-dioxane-4,6-dione) with the subsequent alcoholysis and decarboxylation as described in the publication of a European patent application No. 0418175. The advantage of this method (C) obtain the compounds of formula (III) of imidazolides formula (V) is a higher yield in comparison with the same reaction, in which imidazole formula (V) substituted anhydrides of the formula (VIII).

Compounds of formulas (III) and (V), where R1is phenyl substituted by two or three groups, one of which is 2-S(O)pR6are new and, as such, are the object of the present invention.

The compounds of formula (VI) is known.

According to another variant of the present invention, the method (a) and (b) can be combined to obtain the compounds of formula (I) from compounds of formula (III).

According to another variant of the present invention, the method (A), (b) and (C) can be combined to obtain the compounds of formula (I) from compounds of formula (V).

According to another variant of the present invention, the method (In the ia of the formula (I), obtained according to the methods of this invention can be used to obtain servicenation derivatives of 4-benzoimidazole according to the following reaction scheme:

In the above schemes, R1is cyclopropyl, R2is substituted phenyl and R3is alkyl. 4-Benzoimidazole formulas (IX) and (X) described, for example, in the publications of applications for European patents№ 0418175, 0487353, 0572036, 0560482, 0609798 and 0682659.

The following non-limiting examples illustrate the invention.

Example 1

Obtaining 3-cyclopropyl-1-(4-fluoro-3-methoxy-2-methylthiophenyl)propane-1,3-dione.

A solution of 3-cyclopropyl-1-(4-fluoro-3-methoxy-2-methylthiophenyl)-2-methoxycarbonylamino-1,3-dione (0.15 g) in a mixture of acetonitrile/water (95:5) containing 3 drops of hydrochloric acid (2M), heated under reflux for 44 hours, cooled, dried (magnesium sulfate) and evaporated to obtain the target compound (0.08 g), NMR of 0.9 (m, 2H), 1,1 (m, 2H), 1,65 (m, 1H)that is 2.37 (s, 3H), of 3.96 (s, 3H), 4,15 (s, 1H), 5,9 (s, 1H), 6,95-to 7.15 (m, 2H).

The above compound is also get the same methodology, but using acetonitrile without adding water, from 3-cyclopropyl-2-etoxycarbonyl-1-(4-fluoro-3-methoxy-2-methylthiophenyl with achievement of complete metamorphosis in the target connection (as shown by NMR), but after this time is still 60% of the original complex of ethyl ether.

Example 2

Obtaining 3-cyclopropyl-1-(4-fluoro-3-methoxy-2-methylthiophenyl)-2-methoxycarbonylamino-1,3-dione.

Carbon tetrachloride is added to a suspension of magnesium turnings (0,107 g, 1.1 equivalent) in methanol. Then add a solution of methyl ester 3-cyclopropyl-3-oxopropanoic acid (0,395 g, 1.1 equivalent) in methanol. The mixture is stirred at 60°C for 0.5 hours, cooled, evaporated and re-evaporated after addition of dry toluene to obtain the corresponding enolate magnesium. To a solution of half of enolate magnesium in toluene added a solution of 4-fluoro-3-methoxy-2-methylthiomethyl chloride (0.54 g) in toluene and the mixture is stirred at 20°C for 18 hours, washed (2M hydrochloric acid, then with water), dried (magnesium sulfate) and evaporated to obtain the target compound (0.75 g), NMR 1,1 (m, 2H), 1,38 (m, 2H), and 2.4 (s, 3H), 2,62 (m, 1H), 3,42 (s, 3H), 4,0 (s, 3H), 6,9 (m, 1H), and 7.1 (m, 1H), 17,8 (s, 1H).

Following this methodology, using as starting compound ethyl ester 3-cyclopropyl-3-oxopropanoic acid, receive 3-cyclopropyl-2-etoxycarbonyl-1-(4-fluoro-3-methoxy-2-metaltype the CLASS="ptx2">

Example 3

Getting 2-tert-butoxycarbonyl-3-cyclopropyl-1-(4-fluoro-3-methoxy-2-methylthiophenyl)propane-1,3-dione

A solution of tert-butyl methyl ether 3-cyclopropyl-3-oxopropanoic acid (0.07 g, 1 equivalent) in acetonitrile is added to the magnesium chloride (0.036 g, 1 equivalent) in acetonitrile under stirring in an atmosphere of inert gas. The mixture is cooled to a temperature of 0°C and add pyridine (0,061 ml, 2 equivalents). After 4 hours at a temperature of 0°C. add a solution of 4-fluoro-3-methoxy-2-methylthiomethyl chloride (0.09 g) in acetonitrile. After 0.75 hour, add water and hydrochloric acid (2M) by extraction into ether. The extract is dried (magnesium sulfate) and evaporated to obtain the target compound (0,139 g), NMR 1,1 (m, 2H), 1,18 (s, N), of 1.35 (m, 2H), 2,42 (s, 3H), 4,0 (s, 3H), 6,9 (m, 1H), 7,05-to 7.15 (m, 1H), 17,6 (SHS, 1H).

Example 4

Obtain tert-butyl ester 3-cyclopropyl-3-oxopropanoic acid using ethoxide magnesium as the base.

A solution of mono-tert-butyl ester of malonic acid (0,525 g, 1 equivalent) in tetrahydrofuran is added to a mixture of ethoxide magnesium (0,357 g, 1 equivalent) in tetrahydrofuran and stirred at a temperature of 20°C for 4 hours. After cooling to a temperature of 0°C dobavljaee 1 hour and then at a temperature of 20°C during the night. Add hydrochloric acid (2M) and the mixture is stirred for 0.5 hour, extracted (ether), dried (magnesium sulfate) and evaporated to obtain the target compound (0,519 g), NMR of 0.95 (m, 2H), 1,1 (m, 2H), 1,3 (m, 1H), 1,5 (, N), and 3.5 (s, 2H).

Example 5

Obtain tert-butyl ester 3-cyclopropyl-3-oxopropanoic acid with the use of magnesium chloride and triethylamine as the base.

Mono-tert-butyl ester of malonic acid (0,184 g, 1.2 equivalents) is added to a stirred mixture of dry magnesium chloride (0.084 g, 1.2 equivalents) in dry acetonitrile and the mixture is cooled to 0°C. Add triethylamine (0,204 ml, 2 equivalents) and the mixture is stirred at 0°C for 0.25 hour. Add N-cyclopropanecarboxylate (0.10 g, 1 equivalent) at 0°C and stirring is continued for 1 hour at 0°C, then overnight at 20°C. Add hydrochloric acid (2M) and the mixture extracted (ether), washed (2M solution of sodium hydroxide, then with water), dried (magnesium sulfate) and evaporated to obtain the target compound (0.05 g), NMR of 0.95 (m, 2H), 1,1 (m, 2H), 1,3 (m, 1H), 1,5 (, N), and 3.5 (s, 2H).

Comparative example 5A

Obtain tert-butyl ether is as the base.

Using the method of example 5, but replacing N-cyclopropanecarboxylate cyclopropanecarbonitrile, the analysis of the obtained product showed that the target connection has not been established.

The above experiment demonstrates the undeniable advantage of using N-cyclopropanecarboxylate compared with cyclopropanecarbonitrile.

Example 6

Obtain tert-butyl ester 3-cyclopropyl-3-oxopropanoic acid using magnesium chloride and triethylamine as the base via in situ obtain N-cyclopropanecarboxylate.

The imidazole (0,143 g, 2.2 equivalents) and mono-tert-butyl ester of malonic acid (0,141 g, 1.2 equivalents) is added to a stirred mixture of dry magnesium chloride (0,109 g, 1.2 equivalents) in dry acetonitrile and the mixture is cooled to 0°C. Add triethylamine (0,204 ml, 2 equivalents) and the mixture stirred for 0.25 hour, then add cyclopropanecarbonitrile (0.1 g, 1 equivalent) at 0°C. Stirring is continued for 1 hour at 0°C and then overnight at 20°C. Add hydrochloric acid (2M) and the mixture extracted (ether), washed (2M) solution of sodium hydroxide ).

Reference example 1

Getting 4-fluoro-3-methoxy-2-methyldibenzothiophene.

2,4-Debtor-3-methoxybenzoic acid (38,2 g) added to a mixed solution of methylmercaptan (9.7 g) in dry tetrahydrofuran in an atmosphere of inert gas. Added dropwise a solution of n-utility (162 ml of 2.5 M solution in hexane) at -78°C. After 1 hour, the mixture is heated to a temperature of 20°C overnight and evaporated. Add hydrochloric acid (2M) and ether and the organic phase washed (water), dried (magnesium sulfate) and evaporated. The residue is triturated with hexane to obtain 4-fluoro-3-methoxy-2-methylthiazole acid (29,2 g), NMR of 2.6 (s, 3H), 4,0 (s, 3H), and 7.1 (m, 1H), 7,9 (m, 1H).

Oxalicacid (51,5 g) is added to a stirred solution of 4-fluoro-3-methoxy-2-methylthiazole acid (29,2 g) in dichloromethane. After 3.5 hours, the mixture is evaporated to obtain the target compound (33,0 g) and used directly in the above-described reactions.

Reference example 2

Obtaining N-cyclopropanecarboxylate

The solution cyclopropanecarbonitrile (10.0 g) in dry tetrahydrofuran is added dropwise to a solution of imidazole (13,0 g, 2 equivalents), stirred at 0°C. After 1 hour, the solid is,21 (m, 1H), 7,12(d, 1H), 7,55 (d, 1H), 8.34 per (s, 1H).

Comparative example to illustrate the use of this invention

Getting 5-cyclopropyl-4-(4-fluoro-3-methoxy-2-methylsulfonylbenzoyl)isoxazol.

A mixture of 3-cyclopropyl-1-(4-fluoro-3-methoxy-2-methylsulfinylphenyl)propane-1,3-dione (5,4 g) and triethylorthoformate (4.8 g) in acetic anhydride (4.5 g) is heated under reflux for 4 hours. The mixture is evaporated to obtain 3-cyclopropyl-2-ethoxymethylene-1-(4-fluoro-3-methoxy-2-methylsulfinylphenyl)propane-1,3-dione (6,1 g) as a red oil which is used directly in the next stage.

A similar technique also receive the following link:

3-cyclopropyl-2-ethoxymethylene-1-(4-fluoro-3-methoxy-2-methylthiophenyl)propane-1,3-dione.

Hydroxylamine hydrochloride (1,67 g) and sodium acetate (1.3 g) is added to a stirred solution of 3-cyclopropyl-2-ethoxymethylene-1-(4-fluoro-3-methoxy-2-methylsulfinylphenyl)propane-1,3-dione (6,1 g) in ethanol. After 1 hour, the solvent is evaporated and the residue in ethyl acetate was washed (water), dried (magnesium sulfate) and evaporated. Purification of the residue by chromatography on a column of silica gel with elution by ethyl acetate/hexane (1:1) and rubbing with ethanol is connected:

5-cyclopropyl-4-(4-fluoro-3-methoxy-2-methylthioethyl)isoxazol, so pl. of 62.5-65°C.

1. The method of obtaining the compounds of formula (I)

where one of the groups R1and R2is cyclopropyl and the other is phenyl substituted by two or three groups, which may be the same or different, selected from halogen, nitro, cyano, -(CR4R5)S(O)pR6, -S(O)pR6C1-6alkoxy, C1-4haloalkoxy,1-4of alkyl, C1-4haloalkyl and SF5where p = 0, 1, or 2; R4and R5independently are hydrogen or C1-4the alkyl and R6is1-4by alkyl;

which includes hydrolysis and decarboxylation of compounds of formula (II):

where R1and R2defined above and R3is1-4the alkyl in the presence of water.

2. The method according to p. 1, which is carried out in the presence of a strong acid.

3. The method according to p. 1 or 2, in which the acid is present in a catalytic amount.

4. The method according to any of paragraphs.1-3, in which the reaction is carried out in a polar solvent.

5. The method according to p. 4, in which the polar solvent is acetonitrile.

6. The way Paul>/P>where R1and R3defined in paragraph 1, with a compound of formula (IV)

R2C(=O)X (IV)

where R2defined in paragraph 1;

X is a leaving group,

moreover, the method is carried out in the presence of a magnesium halide and a base.

7. The method of obtaining the compounds of formula (III) under item 6, where R1is cyclopropyl, which includes the interaction of the compounds of formula (V)

where R1is cyclopropyl;

Y is substituted or unsubstituted imidazol-1-ilen ring,

with the compound of the formula (VI)

where R3defined in paragraph 1, through the decarboxylation of compounds of formula (VII)

where R1is cyclopropyl and R3defined in paragraph 1.

8. The method according to p. 7, where Y is imidazol-1-yl.

9. The method according to p. 7, in which the compound of formula (VII) decarboxylate into the presence of a strong acid.

10. The method according to p. 7 or 8, which is carried out using complex metal compounds of the formula (VI).

11. The method according to p. 10, in which the complex metal is a complex magnesium.

12. The method according to p. 10, which is carried out using halogen ora is substituted by phenyl, choose from 2-S(O)pCH3, 4-CF3; 2-S(O)pCH3, 3-OCH3, 4-F; 2-CH2S(O)pCH3, 4-Br; and 2-NR2A 4-S(O)pCH3substituted phenyl.

14. The method according to any of paragraphs.1-6, where the group R1or R2which is substituted by phenyl, which are selected from 2-S(O)pCH3, 4-CF3; and 2-S(O)pCH3, 3-OCH3, 4-F substituted phenyl.

15. The method according to any of the preceding paragraphs, in which R3is stands or ethyl.

16. The method according to p. 1, in which the compound of formula (II) are obtained by the method according to p. 6.

17. The method according to p. 16 in which the compound of formula (III) used in the method according to p. 6, get way under item 7.

18. The method according to p. 6, in which the compound of formula (III), where R1is cyclopropyl get way under item 7.

19. The compound of General formula (II)

where R1and R2defined in paragraph 1 and R3is C1-3the alkyl.

 

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The invention relates to new derivatives of balkanov General formula (A)

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where Ar is phenyl which may be unsubstituted or substituted one, two or three substituents independently chosen among Cl, Br, F, -OMe, NO2, CF3C1-4lower alkyl, -NMe2, -NEt2, -SCH3, -NHCOCH3; 2-thienyl, 2-furyl; 3-pyridyl; 4-pyridyl or 3-indolyl; R-OCH2R1where R1choose from a number of-CH= CME2The CME=CH2-The CCH; provided that when Ar is a phenyl,4-alkylphenyl, 4-methoxyphenyl or 3,4-acid, R can be any except 3-methyl-2-butenyloxy

The invention relates to a method for 5,5'-(oxydi)pentanone-2, which can be used as polyfunctional solvent, extractant, as a fragrant substance and as a feedstock for the synthesis of heterocycles

The invention relates to an improved process for the preparation of CIS-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl] ethyl} pyrrolidine, which is a substance to obtain the (-)CIS-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl-5,6,7,8-tetrahydronaphthalen-2-ol, which is used in the treatment of osteoporosis, as well as to intermediate compounds for this method

The invention relates to a new method of obtaining galijasevic connection hydroxydiphenyl, which are used to combat microorganisms

The invention relates to a new method for producing a halogen-o-hydroxydiphenyl compounds of formula (1) in which X Is-O - or-CH2-, m = 1-3, n = 1 or 2, which are used for protecting organic materials from microorganisms, and new acyl compounds of the formula (8), which are intermediate products in which R is unsubstituted C1-C8alkyl substituted with 1-3 atoms of halogen or hydroxy; or unsubstituted WITH6-C12aryl or6-C12aryl substituted by 1-3 halogen atoms, WITH1-C5the alkyl or C1-C8alkoxy

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The invention relates to new immunotherapeutics compounds of the formula

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in which X represents-O - or -(CnH2n)-, in which n is 0, 1, 2 or 3; R1represents alkyl containing from 1 to 10 carbon atoms, or monocyclohexyl containing up to 10 carbon atoms; R2represents hydrogen, lower alkyl or lower alkoxy; R3represents (1) phenyl or naphthalene, unsubstituted or substituted by one or more than one Deputy each independently selected from nitro, halogeno, amino, amino substituted by alkyl containing 1-5 carbon atoms, alkyl containing up to 10 carbon atoms, cycloalkyl containing up to 10 carbon atoms, alkoxy containing up to 10 carbon atoms, cycloalkane containing up to 10 carbon atoms, phenyl or methylendioxy; (2) pyridine; each of R4and R5taken separately, represent hydrogen, or R4and R5taken together, represent a carbon-carbon bond; Y is-COZ, -CN or lower alkyl containing from 1 to 5 carbon atoms; Z represents R7represents an alkyl

The invention relates to a method for producing 5-alkoxyethanol-2 formula CH3WITH(CH2)3OR, where R = CnH2n+1n = 1-10, the interaction of acetylchloride (ADC) with a monohydroxy alcohol R-OH in the presence of palladium catalyst in water in the presence of the source of the alcohol R-OH as solvent or water-air environment at a temperature of 165-200°C for 6-60 hours at a molar ratio of the components: [ADC]:[R-HE]:[H2O]:[cat]:[solvent] = 1:1: (3-8) : (0,005-0,01) : (2-9), where R = CnH2n+1(n = 1-3) solvent - the corresponding alcohol, and when n4 solvent: diethyl ether

The invention relates to new substituted derivatives of bicycloheptadiene and herbicides containing the derivatives as an active ingredient

The invention relates to organic chemistry, analytical chemistry and immunoassay and represents a new connection, which may find application as a reagent for precision fluorimetric determination of small concentrations of europium, and also as a component for a solution, amplifying the signal of self-fluorescence of europium ions, when conducting lanthanide fluorescence immunoassay with a temporal resolution of

-diketones and ketoesters" target="_blank">

The invention relates to the chemistry of adamantane derivatives, and in particular to a new method of obtaining-dicarbonyl derivatives of adamantane General formula

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where R=CH3:R1=CH3OC2H5; R=C6H5: R1=OC2H5C6H5, CF2H

R=CF3:R1=C6H5n-C6H4C1

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which are the products for the synthesis of biologically active substances
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