-polyfluoroankyl-nitroaniline and method of production thereof

 

(57) Abstract:

Describes the polyfluoroankyl--nitroaniline and their derivatives, which can be used as reagents for the synthesis of compounds with potential biological activity, the General formula

RFCHN(R1R2)CHRNO2,

where RF= CF3C2F5C3F7C4F9C6F13H(CF2CF2)nwhere n = 1,2,3; R = H, alkyl (C1- C4, Ph; R1= H, HHCl; C(O)R3where R3= H, alkyl (C1-C6, Ph; R2= H; R1+R2= ftail,

and the way they are received, wherein the NITRILES poliftorirovannykh acid is subjected to interaction with the sodium salts of nitroalkanes in 1,4 - dioxane, and then subjected to interaction with sodium borohydride and acetic acid in benzene in the ratio of sodium borohydride: acetic acid 1: 0.75 to 1 emitting products known methods. 2 S. and 1 C.p. f-crystals, 2 tab.

The invention relates to organic chemistry, specifically to new chemical compounds - polyfluoroankyl--nitroanilines and their N-ACI-derivatives of the General formula 1

< / BR>
where (a) RF=CF3; C2F5; C3F, h;

R1=H; C(O)R3where R3=H, alkyl (C1-C6Ph;

R2=H;

< / BR>
b) RF=C2F5; C3F7; C4F9; H(CF2CF2);nwhere n=1,2,3;

R1=HHCl;

R2=H.

which can be used as intermediate products in the synthesis of biologically active compounds.

These compounds may be used, in particular, to obtain a fluorine-containing analogues of amino acids by transformation nitromethylene carboxyl group in the same way as is described in the famous work /S. Sabelle, D. Luset, T. Le Gall, Ch. Mioskowski. "Enantioselective synthesis of a-aminoacids from nitroalkenes". Tetrahedron Lett. 1998, v. 39.P. 2111-2114/. Fluoride-aminosilane and their analogues are of considerable interest as substances with biological activity. /"Fluorine compounds. Synthesis and application". Under.ed. N. Ishikawa. M; World. 1990. C. 306-337/. From this point of view, the claimed compounds can be considered as precursors of fluorinated amino acids, which determines the possible aspects of their practical use.

The closest analogue of the structure is hydrochloride 1,1,1-Cryptor-2-amino-3-nitropropane formula (2), which is used in the body of the 3-nitropropenes and reaction with enamines" Zhur.org.chem. 1987. So 23. N 6. C. 1331-1332/

< / BR>
The method of obtaining the compounds of formula (2) is in the interaction of freshly prepared sodium salt of nitromethane in tetrahydrofuran with cryptorchidism in the presence of chloride triethylenediamine. Formed - nitroenamine allocate treatment of the reaction mixture with a solution of H2SO4in tetrahydrofuran, followed by distillation in vacuum. Then the product is dissolved in benzene and added NaBH4and a catalytic amount of methyl tetrabutylamonium. Stirred for 6 h at 40-50oC, filtered and the filtrate miss HCl to stop shedding amine hydrochloride. The residue is filtered and crystallized from ethanol. Yield 59%, so pl. 106-107oC /Aizikovich A. J., Bazyl ' And. So 1,1,1-Cryptor-2-diazo-3-nitropropane - synthesis and reactions with enamines. Zhur.org.chem. 1987. T. 23 N 6. C. 1331-1332/.

Object of the invention is the synthesis of a new group of compounds that can serve as initial products to obtain substances with potential biological activity, in particular fluorinated analogues of amino acids.

This object is achieved by the structure of new compounds, namely the presence of polyporales Deputy nitromethylene and amino groups, is home to the thrill politicalanomaly acid is subjected to interaction with the sodium salt of the nitroalkane in 1,4-dioxane, and then subjected to interaction with sodium borohydride and acetic acid in benzene with the release of the final products by the known methods, however preferably the ratio of sodium borohydride-acetic acid is 1: 0.75-1. N-Derivatives of amines were obtained by the interaction of hydrochloride amines of General formula (1) with carboxylic acid anhydrides in the presence of basic agents.

All compounds are crystalline substances stable in the long term. Their structure is clearly established methods of elemental analysis and NMR1H and19F-spectroscopy (tables 1, 2).

Example 1. Getting hydrochloride 1,1,1-Cryptor-2-amino-3-nitropropane.

To a suspension of 8.3 g (0.1 mol) of sodium salt of nitromethane in 100 ml of dry 1.4-dioxane 30-40 min missed triptoreline obtained simultaneously from 20.0 g (0.15 mol) of amide triperoxonane acid and 21.3 g (0.15 mol) of P2O5. Then the reaction mixture was stirred for 0.5 h in the presence of 0.1 g (3 10-4mol) of tetrabutylammonium bromide, and then slowly added 2.7 ml (0.05 mol) of concentrated sulfuric acid, cooling the reaction mixture on a water bath with ice. The precipitation sulfa the rim of the enamine, was dissolved in 60 ml of dry benzene and slowly under stirring was added to a suspension of 3.7 g (0.1 mol) of NaBH4in 60 ml of dry benzene. After adding the whole amount of a solution of the enamine reaction mass was stirred 30 min, then was slowly added dropwise a solution of 6.0 ml (0.1 mol) of acetic acid in 50 ml of dry benzene was stirred another 30 min at room temperature and 1.5-2 h at 50-60oC, cooled to room temperature, the precipitate was filtered, and through the filtrate was barbotirovany dry HCl. Precipitated hydrochloride was filtered and recrystallized from ethanol. Output, and so pl. is shown in table 1, and the range of PMR in table 2.

Example 2. Getting 1,1,1,2,2,3,3,4,4,5,5,6,6-traducator-7 - amino-8-nitroethane.

To a suspension of 8.3 g (0.1 mol) of sodium salt of nitromethane in 200 ml of 1,4-dioxane with stirring was bury 34.5 g (0.1 mol) of nitrile performative acid for 3 h in the presence of 0.1 g (3 10-4mol) tetrabutylammonium bromide. After adding the entire amount of the nitrile, the reaction mixture was stirred 30 min, then was slowly added 2.7 ml (0.05 mol) of concentrated sulfuric acid, cooling the reaction mixture on a water bath with ice. The precipitation of sodium sulfate ethyltrichlorosilane, dried, dissolved in 100 ml of dry benzene and slowly under stirring was added to a suspension of 3.7 g (0.1 mol) of NaBH4in 100 ml of dry benzene. After adding the whole amount of a solution of the enamine reaction mass was heated for 6 h, and then, without stopping the heating, was slowly added dropwise a solution of 6.0 ml (0.1 mol) of acetic acid in 50 ml of dry benzene was stirred another 30 min at room temperature and 1.5-2 h at 50-60oC, again cooled to room temperature, the precipitate was filtered, and through the filtrate was barbotirovany dry HCl. The precipitation of the free amine was filtered and recrystallized from ethanol. Output, and so pl. is given in table. 1, and the spectrum of the PMR - in table. 2.

Example 3. Obtain 1,1,1-Cryptor-2-(N-benzoyl)amino-3-nitropropane.

A mixture of 8.1 g (0.05 mol) of the hydrochloride 1,1,1-Cryptor-2-amino-3-nitropropane and 7.0 (0.05 mol) of benzoyl chloride was boiled for 4 hours in 50 ml of benzene in the presence of 7.9 g (0.1 mol) of pyridine, after which the solvent was evaporated in vacuum at 10-15 mm RT.art., and the residue was washed with a saturated solution of NaCl. The precipitation was filtered off, washed with cold ether, dissolved in chloroform, was added hexane, precipitated precipitate was filtered. Output, and so pl. shown in the tables is 1 and 2, there were obtained similar methods.

1. -Polyfluoroankyl--nitroaniline and their derivatives of General formula

< / BR>
where (a) RF= CF3; C2F5; C3F7; C4F9; C6F13; H(CF2CF2)nwhere n = 1, 2, 3;

R = H, alkyl WITH1-C4Ph;

R1= H, C(O)R3where R3= H, alkyl WITH1-C6Ph;

R2= N,

or

< / BR>
or b) RF= C2F5; C3F7; C4F9; C6F13; H(CF2CF2)nwhere n = 1, 2, 3;

R1= HHCl,

R2= H.

2. Way to obtain-polyfluoroankyl --nitroaniline General formula

< / BR>
where (a) RF= CF3; C2F5; C3F7; C4F9; C6F13; H(CF2CF2)nwhere n = 1, 2, 3;

R = H, alkyl WITH1-C4Ph;

R1= H, C(O)R3where R3= H, alkyl WITH1-C6Ph;

R2= N,

or

< / BR>
or b) RF= C2F5; C3F7; C4F9; C6F13; H(CF2CF2)nwhere n = 1, 2, 3;

R1= HHCl

R2= H

characterized in that the nitrile corresponding politicalanomaly acid is subjected to the view with sodium borohydride and acetic acid in benzene, followed, where appropriate, processing the obtained compounds hydrogen chloride to obtain hydrochloride of the compound of formula I, which optionally may be treated with acid chloride of the corresponding carboxylic acid in the presence of a basic agent, and the release of the final product.

3. The method according to p. 2, wherein the process is conducted at a molar ratio of sodium borohydride and acetic acid is 1 : 0.75 to 1, respectively.

 

Same patents:

The invention relates to new derivatives of demineralised General formula 1

< / BR>
where A1and A2independently of one another denote hydrogen, lower alkyl, lower alkenyl or lower alkanoyl; or where A1and A1together denote C1-C4alkylen;

Ar1and Ar2independently of one another denote phenyl, optionally substituted by one or two substituents selected from the group phenyl, halogenosilanes lower alkyl, hydroxyl, lower alkoxyl, phenyl(lower)alkoxy, halogen, nitro, amino, di(lower)alkylamino and cyano; or C3-C8cycloalkyl;

X denotes oxygen or sulfur; and

R denotes hydrogen, lower alkyl, phenyl(lower)alkyl or amino, or their pharmaceutically-acceptable salts, and pharmaceutical compositions based on these compounds exhibiting inhibitory effect on proteincontaining or serine-trionychinae suitable for use in the pharmaceutical industry and in veterinary medicine

The invention relates to an improved process for the preparation of N-(cyclohexylthio) phthalimide formula (1)

The invention relates to organic chemistry, in particular to a method of obtaining an individual stereoisomers of 4-diprosone glutamic acid of General formula

< / BR>
< / BR>
ALK is a lower alkyl

The invention relates to the field of synthesis of organic compounds-4-halogenated derivatives of glutamic acid (GA) the General formula I,

< / BR>
Alk alkyl, x is halogen, P protecting group, namely the synthesis of dimethyl (2S, 4RS)-N-phthaloyl-4-adglutinata acid of the formula II,

< / BR>
which can be used as sintana to obtain C4-derivatives of GA, has anticancer, radioprotective, and other types of biological activity /1-3/, and to a method for obtaining compounds of formula II

The invention relates to the derivatives of benzene, substituted heterocyclic ring represented by the General formula

XZ (1) where R cycloalkyl group having 3-8 carbon atoms;

X halogen atom;

The Z group of the formula

-Nor-Nin which cycloalkyl group may be substituted by an alkyl group having 1-6 carbon atoms, to a process for their preparation and herbicides containing them as active ingredient

The invention relates to methods for bisimide 2,2-bis[4- (3,4-dicarboxyphenoxy)phenyl] propane (abbreviated) bis(everflame), which is the intermediate for the synthesis of the dianhydride And the monomer to the thermoplastic polyetherimide [1] with excellent performance characteristics: high temperature resistance, good electrical properties, high fire resistance (oxygen index 47)

The invention relates to florenceville compounds of General formula (X)(Y)C=C(Z)-(CH2)n-Q(I), where X and Y are fluorine; Z is hydrogen, fluorine; n= 1, 3, 5, 7, 9, 11; Q-CH2OTHER6CH2NO2, CHN=CHR2CY2N=C=O, CH2N+R3R4R5W - (C=O)-R11provided that if X and/or Y is fluorine and Q is-(C=O)-R11each X, Y, Z is fluorine, and n = 1, W is the anion of a mineral or organic acid; R2possibly substituted phenyl, R3, R4, R5is hydrogen and the other, R6is hydrogen, (C1-C6)-alkyl, and others, R11-halogen, NHOH, and others, and to their agricultural acceptable salts

The invention relates to the field of organic chemistry, and in particular to a method for producing amides of unsaturated acids of the General formula 1

Q Q1CR2= CR3CR4= CR5C(X) OTHER1(1) or their salts, where Q denotes phenyl, pyridyl, naphthyl, degloving, each of which may be substituted by 1-3 substituents selected from the group:1-C6alkyl, C1-C6alkoxy, CF3, halogen, Q1-1,2-cyclopropyl ring, possibly substituted C1-C4the alkyl, R2, R3, R4and R5denote identical or different groups, including hydrogen, C1-6alkyl group, or C1-6 haloalkyl group; one of the radicals necessarily mean hydrogen, X denotes an oxygen atom, R1denotes hydrogen or C1-6the alkyl may contain as substituents DIOXOLANYL group, cyclo(C3-C6)alkyl, possessing insecticidal activity

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention describes dialkylamide derivatives of pyrethroid acids of the general formula (III): wherein R1 and R2 represent organic radicals and each radical represents ethyl, or they both can be bound and in common with nitrogen atom represent piperidide, hexamethyleneimide, morpholide. Represented compounds are used as chemical agents for control of insect-pests in agriculture, veterinary science and cattle breeding.

EFFECT: valuable properties of compounds.

2 dwg, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns chemistry of adamantane derivatives, namely to a new method of obtaining of dialkylamides of 3-brome-1-adamantilalkancarbon acids of the general formula:

R1,R2=H:R3=N(C2H5)2

R1, R2=CH3:R3=N(C2H5)2

which can be of interest as semiproducts in synthesis of some biologically active substances possessing antiviral activity. Method lies in interaction of 1,3-dehydroadamantane with dialkylamides of α-bromalkancarbon acids from the row: diethylamide of α-bromacetic acid, piperidide of α-brompropionic acid, diethylamide of α-bromo-isobutyric acid at mole ratio of reagents peer accordingly 1:3-4, in the environment of the initial dialkylamides of α-bromalkancarbon acids, at temperature of 80-90°C within 4-6 hours.

EFFECT: obtaining of bonds of declared structural formula, excluding reception stage adamantilealkanecarbon acids.

3 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to chemistry of adamantine derivatives, namely, to a method for preparing N-phthalimidoalkyladamantane or its derivatives of the general formula: wherein X means a single bond; R1 means hydrogen atom (H); R means C6H5, C6H4COOC2H5; R1 means CH3; R means CH3; R1 means COOC2H5; R means CH2CH2SCH3, (CH2)3CH3; X means CH2CH2; R1 = R means COOC2H5; X, R1 mean ; R means COOC2H5 that represent important intermediate products in synthesis of biologically active substances. Method is carried out by adding corresponding N-phthalimidoalkyl or its derivative to a derivative of adamantine. 1,3-Dehydroadamantane is used as a derivative of adamantine, and the following compounds are used as N-phthalimidoalkyl or its derivative: N-benzylphthalimide, N-isopropylphthalimide, ethyl esters of N-phthalyl-D,L-methionine, N-phthalyl-D,L-norleucine, N-phthalyl-4-aminomethyl-1-benzoic acid, N-phthalyl-4-aminocyclohexane 1-carboxylic acid, 2-(N-phthalimido)-ethylmalonic acid ethyl ester. Process is carried out in the mole ratios of reagents = 1:(2-3), respectively, in inert solvent medium, at temperature 80-120oC for 4-6 h.

EFFECT: improved preparing method, enhanced yield of end compounds.

7 ex

FIELD: organic chemistry, dyes.

SUBSTANCE: invention relates to the dispersed dyes comprising N-methylphthalimide-diazo-component and a coupling aniline component. Invention proposes a dye of the formula (1): wherein R means hydrogen or bromine atom; R1 means hydrogen atom, methyl or -NHCO-(C1-C4)-alkyl; R2 means (C1-C4)-alkyl substituted with (C1-C4)-alkoxy-group; R3 has any value among R2 being independently of R2. Invention proposes a mixture of dyes comprising at least one azo dye of the formula (1) and at least one azo dye of the formula (4): wherein R1 means hydrogen atom, methyl or -NHCO-(C1-C4)-alkyl; R2 means (C1-C4)-alkyl wherein is possible but not obligatory that C2-alkyl chain or comprising more carbon atoms is broken with oxygen atom, and R has any value of R being independently of R2. Also, invention proposes a method for coloring or printing on semisynthetic or synthetic hydrophobic fibrous materials wherein dye of the formula (1) or mixture of dyes of formulae (1) and (4) is applied on such materials or added in them. Invention proposes dispersed dyes providing coloring characterizing by high strength degree in laundry and against sweat.

EFFECT: valuable properties of dyes.

7 cl, 2 tbl, 3 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to phthalimido-derivatives of the general formula (I): wherein X means -N= or -CH=; R1 means -CO-NR5R6, -CHR7-(CH2)n-CO-NR5R6, -(CH2)n-NR5R6, -(CH2)n-COOR8, -(CH2)n-CN, -CHR7-(CH2)n-CF3, -(CH2)n-NH-COR9, -(CH2)n-NH-COOR8, -(CH2)n-piperidinyl, -(CH2)n-morpholinyl, -(CH2)n-tetrahydrofuranyl, -(CH2)n-thiophenyl or -(CH2)n-isoxazolyl wherein a heterocyclic ring can be substituted with (C1-C6)-alkyl; -(CH2)n-phenyl wherein phenyl ring can be substituted with halogen atom or halogen-(C1-C6)-alkyl; -(CH2)p-OR8, -(CH2)p-SR8, -(CH2)p-SO-R9 or -(CH2)n-CS-NR5R6; R2 means hydrogen atom (H), (C1-C6)-alkyl, -(CH2)p-OR10, -(CH2)p-SR or benzyl; R3 means H, (C1-C6)-alkyl; R4 means halogen atom, halogen-(C1-C6)-alkyl, cyano-, (C1-C6)-alkoxy- or halogen-(C1-C6)-alkoxy-group; Each R5 and R6 means independently of one another H, (C1-C6)-alkyl; R7 means H, -OH, (C1-C6)-alkoxy-group; R8 means H, (C1-C6)-alkyl; R9 means (C1-C6)-alkyl; R10 means H, (C1-C6)-alkyl; m = 1, 2 or 3; n = 0, 1 or 2; p = 1 or 2, and their pharmaceutically acceptable salts. Compounds of the formula (I) inhibit activity of monoamine oxidase B (MAO B) that allows their using as a drug.

EFFECT: valuable medicinal and biochemical properties of compounds.

14 cl, 4 sch, 1 tbl, 53 ex

FIELD: organic chemistry, biochemistry, medicine, virology.

SUBSTANCE: invention relates to a compound of the general formula: (R1)-(R2)-N-CH-(CH=CH2)-CH2R3 wherein R1 represents alkoxycarbonyl, arylalkoxycarbonyl, aryloxycarbonyl, benzoyloxycarbonyl; R2 represents hydrogen atom (H), or R1 and R2 in common with nitrogen atom to which they are joined form phthalimido, succinimido or N-diformyl group; R3 represents thioalkyl or thioaryl. Also, invention relates to a method for synthesis of compounds represented by the formula (8): that involves the following steps: (a) treatment of hydroxybutene of the formula (6): with methanesulfonyl chloride in the presence of an amine base in a polar aprotonic solvent to obtain butene mesylate of the formula (7a): wherein R' represents alkyl or aryl, and (b) treatment of butene mesylate (7a) with thiophene oxide wherein thiphene is formed in situ using thiophenol and non-nucleophilic base in polar aprotonic solvent to obtain thiophenylbutene (8). Also, invention relates to a method for stereoselective conversion of compound of the formula (8) to compound of the formula (9): or the formula (10): wherein this method involves treatment of compound of the formula (8) with osmium-containing oxidizing combination of reagents: K2OsO2(OH)4/K3Fe(CN)6, K2CO3, NaHCO3 and CH3SO2NH2 in the presence of DHQD2PHAL as a chiral accessory reagent to obtain compound represented by he formula (9) or the formula (10). Invention provides synthesis of butene and butane compounds that are useful as intermediate compound in synthesis of nelfinavir mesylate relating to a protease inhibitor.

EFFECT: improved methods of synthesis.

8 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to extraction of M-(chloralkylthyo)phthalimides, which are efficient anti-scorchers for synthetic and natural rubber. N-(chloralkylthyo)phthalimide is extracted from the mix with phenyl chloride by distillation of the latter. The distillation is effected in vacuum in azeotropy with water in the presence of surfactant in the amount of not over 0.33% relative to added water volume.

EFFECT: increase in vacuum azeotropic distillation intensity and higher power saving.

3 tbl, 30 ex

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