The method of obtaining n,n-diethylmetatoluamide

 

(57) Abstract:

The inventive product is N, N-diethylmetatoluamide. Reagent 1: m-tolarova acid. Reagent 2: diethylamin. Reaction conditions: diethylamin served in a mixture with a solvent (benzene, toluene, m-xylene) in the ratio 1:1 under the layer of the reaction mixture with vigorous stirring at 200 - 220oWith continuous and direct the azeotropic distillation of the mixture of solvent, water and unreacted diethylamine in the presence of a catalyst-complexing compounds P(3), or B.

The invention relates to methods of obtaining N,N-diethyl-meta-toluamide (DETA), which is one of the best repellents, and can be used in the chemical and pharmaceutical industries.

A method of obtaining DEATH metal, which consists in the interaction m-Truelove acid (MTC) with thionyl chloride or other gloriously agents (l3, COCl2c the formation of the acid chloride m-Truelove acid, separation, distillation and further processing the last diethylamino with subsequent vacuum distillation of the obtained raw DEATH metal [1]

The disadvantage of this method is the use of a large number gloriously agents, strong corrosion of the rim, solid waste, including vacuum-evaporating device of the acid chloride m-Truelove acid, and gaseous emissions containing Hcl and SO2.

Also known more promising method of obtaining DATA from m-Truelove acid without intermediate formation of the acid chloride in the presence of titanium compounds (of 0.0001-0.1 g per 1 g MTC). Use TiCl4, Ti(OAlk)4where Alk C3-C18, complex compounds of titanates with triethanolamine, tetraethyleneglycol; titanium acetylacetonate. The process is conducted in an organic solvent azeotropic distillation of water and solvent recovery. Output DETA 68-74% [2]

The advantage of this method is the exception to the stage of obtaining the acid chloride, which leads to the reduction of aggressive waste.

The disadvantage of this method is the use as catalysts of toxic titanium compounds that can get into the final product, as well as the duration of the process at a fairly high temperature (220-235aboutWith over 40 hours). Technological design method using a nozzle Dean-stark to return the solvent to the reaction mass does not allow sufficiently removed from the reaction mass water due to the formation of ternary mixture of the reaction (conversion of 93% yield 68-74%).

The invention allows to reduce the duration of the process, to reduce the temperature of the process, to use more available and cheaper catalysts, as well as to increase the output of diethyltoluamide.

The essence of the proposed method lies in the fact that N,N-diethyl-meta-toluamide produced by the interaction meta-Truelove acid with diethylamine when heated (200-220about(C) in the presence of a catalyst (compounds 3-valent phosphorus and boron) and a solvent, forming an azeotrope with eye-catching during the reaction with water, when the continuous supply of diethylamine in a mixture solvent (1: 1) under a layer of reaction mass at a temperature of 200-230aboutWith and in continuous distillation of a mixture solvent of water and unreacted diethylamine through direct refrigerator with a reflux condenser, which contributes to more complete removal of water from the reaction mass and a shift in the equilibrium towards formation of diethyltoluamide.

The condensate can then be regenerated.

P R I m e R 1. 50 g (0.36 m) m-Truelove acid, 1 ml of diethylamine and 1 ml of xylene, 1,25 g H3RHO3(0,015 m) are loaded into a flask of 250 ml, equipped with a stirrer, thermometer, addition funnel for reagent supply under layer Rea is Argonaut azeotrope with xylene excess moisture from m-Truelove and of phosphorous acid and at a temperature of 200aboutFrom start to apply under the layer of the reaction mixture, a mixture of diethylamine with xylene (1:1). Formed during the reaction water azeotrope is distilled off with xylene and unreacted by diethylamino. The condensate is collected in a receiver and then subjected to regeneration. Duration of response of 9 o'clock

After the reaction mass is then cooled to a temperature of 60aboutC and washed with 50 ml of 25% aqueous sodium chloride solution containing 1 l 1.1 g sodium hydroxide. Stirred at 60about1 h, transferred into a separating funnel and separate the lower aqueous layer, which then goes on acidification and isolation of unreacted m-Truelove acid. The upper layer containing diethyltoluamide, washed again with 40 ml of 25% aqueous solution of sodium chloride at 60aboutC, divided by a separating funnel. The organic layer containing DETA, is subjected to vacuum rectification. Basic fraction Argonauts at a residual pressure: 5 mm at 133aboutC, 10 mm at 146-148aboutC.

Get a 58.3 g of DETA with the content of the main product 98%

Conversion ITC 96%

Output DETA 83% loaded acid, 86.5% of the new reaction.

P R I m m e R 2. 50 g m-Truelove acid, 1 ml of diethylamine, 1 ml of benzene and 1.25 g of phosphorus is with benzene (1:1). The reaction takes place analogously to example 1. Duration of 8 hours Output DETA 81% loaded on acid.

P R I m e R 3. In the examples 1 and 2 begin to apply the mixture of diethylamine with toluene at 200aboutC. the Reaction proceeds analogously to examples 1 and 2. The results of the process similar to example 1.

P R I m e R 4. 30 g (0,217 m) m-Truelove acid, 2 ml of benzene, 2.35 g (0,017 g-m) trichloride phosphorus load into a flask of 100 ml, equipped as described in examples 1 and 2, and at 200aboutServed with a mixture of m-xylene/diethylamine under the layer of the reaction mass. After 7 h, the conversion of m-Truelove acid is 97.5%

P R I m e R 5. The 4-necked flask with a capacity of 250 ml, equipped as described in example 1, a reflux condenser, a load of 50 g m-Truelove acid, 1.5 g of boric acid and 1 ml of diethylamine and m-xylene. The reaction mass is heated until complete melting MTC when stopped the mixer, then the mixer and continue heating. At a temperature of 220aboutFrom start to dispense a mixture of diethylamine with m-xylene in the amount of 150 ml and a 1:1 ratio. Loading the mixture is held for 7 hours at a temperature of 220aboutC. during the reaction is carried out continuous removal of unreacted diethylamine, m-xylene and reacts is 15 minutes, then poured into a separating funnel, separate the organic layer from the water containing Na-salt of unreacted m-Truelove acid and conduct vacuum distillation, selecting the main fraction at a temperature of 151aboutC and a vacuum of 10 mm RT.article Get to 46.8 g trademark DEATH metal containing 95,25% m-DETA, representing 80.6% of the downloaded MTC.

P R I m e R 6 (comparative). In conditions of experiments 1 and 2 the mixture flow diethylamine with the solvent is carried out at 180aboutC. After 20 h the reaction mixture was detected 12% DETA.

P R I m e R 7 (comparative prototype). 50 g (0.36 m) m-Truelove acid, 6.5 g of diethylamine (0,09 m) and 0.36 g of phosphorous acid are loaded into a flask of 250 ml with a nozzle Dean-stark, filled with benzene and a reflux condenser. The reaction mixture is heated to melting m-Truelove acid and stirred for 22 hours at a temperature of 220-235aboutC. In the first 3-4 h observed the separation of water from the reaction mass and defending her in the nozzle Dean-stark, then a couple of benzene, water and diethylamine form nonshared mixture.

Diethylamine (25 g, 0,37 m) served under a layer of the reaction mixture for 18 hours After exposure of the reaction mass is treated as described in example 1. Get 11,98 ocrotiti the duration of the process from 35-40 to 7-10 hours at the temperature decrease with 220-235 to 200-220aboutTo use available and cheap catalysts (compounds 3-valent phosphorus and boron H3PO3, PCl3, POCl3H3BO3. In addition, the technological design of the method, it is permanently removed from the reaction mass of water with the solvent and excess diethylamine allows you to increase the conversion-Truelove acid up to 96-99% and, accordingly, to increase the output of diethyltoluamide.

The METHOD of OBTAINING N,N-DIETHYLMETATOLUAMIDE the interaction of metatoluidine acid with diethylamine at 200 - 220oIn the presence of a catalyst and solvent - aromatic hydrocarbon azeotropic distillation of the water formed, characterized in that diethylamin served in the mixture with the solvent in a ratio of 1 : 1 under the layer of the reaction mixture with vigorous stirring and continuous direct the azeotropic distillation of the mixture of solvent, water and unreacted diethylamine, at the same time as the catalyst is used complexing compound of trivalent phosphorus or boron, and as the aromatic solvent is benzene or toluene, or betaxolol.

 

Same patents:

The invention relates to new chemical compound is 4-bromoaniline N-allyl-N-(adamantyl-1' ) Anthranilic acid of the formula I

exhibiting anti-inflammatory and analgesic activity

The invention relates to chemistry, specifically to an improved method of obtaining benzamide

The invention relates to methods for new therapeutically active derivatives of benzanilide General formulawhere R1- alkyl WITH4-C18with a linear or branched alkyl group which may have a double bond,

R2is hydrogen, methyl or ethyl,

R3- halogen, alkyl WITH1-C5with a linear or branched alkyl group, N(CH3)2, OS or SY, where Y1-C4alkyl linear or branched chain,

R4and R5each independently is hydrogen, alkyl WITH1-C6with a linear or branched alkyl group or a group -(CH2)m-Z, in which Z is a group of the formula och3, -S(O)qСН3or N(CH3)2q= 0,1 or 2, and m= 2,3 or 4, or Z is a 5 - or 6-membered heterocycle containing nitrogen atom, oxygen or sulfur

The invention relates to the chemistry of obtaining amides sorbic acid (TRANS, TRANS-2,4-hexadienoic acid), in particular the production of N,N-di(cyclohexyl)amide sorbic acid of the formula (N GOS

The invention relates to a method for producing complex organic esters or amides of certain organic esters
The invention relates to organic chemistry, specifically to an improved process for the preparation of N-(chloroacetyl)-2,6-dimethylaniline [N-(chloroacetyl)2,6-xylidine] which is an intermediate for the synthesis of drugs (Patents England N 634072, 634073, 705460, 730753, 754413, 7582224, 765544, 793201, 1309874, Sweden N 128901, USA N 2441498 and others), biologically active compounds (U.S. Patent N 4831054, Borovansky A

The invention relates to chemistry, specifically to an improved method of obtaining benzamide

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein Ar represents phenyl substituted with a group taken among isobutyl, benzoyl, isopropyl, styryl, pentyl, (2,6-dichlorophenyl)-amino-group, α-hydroxyethyl, α-hydroxybenzyl, α-methylbenzyl and α-hydroxy-α-methylbenzyl; R represents hydrogen atom; X means linear (C1-C6)-alkylene, (C4-C6)-alkenylene, (C4-C6)-alkynylene optionally substituted with group -CO2R3 wherein R3 means hydrogen atom, group (CH2)m-B-(CH2)n wherein B means oxygen atom; m = 0; n means a whole number 2; or B means group -CONH; m means a whole number 1; n means a whole number 2 and so on; R1 and R2 are taken independently among group comprising hydrogen atom, linear (C1-C4)-alkyl, hydroxy-(C2-C3)-alkyl and so on. Invention proposes a method for preparing compounds of the formula (I). Invention proposes inhibitors of C5-induced hemotaxis of polymorphonuclear leukocytes and monocytes representing (R)-2-arylpropionic acid omega-aminoalkylamides of the formula (I). Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to hemotaxis of polymorphonuclear leukocytes and monocytes and comprising compounds of the formula (I) in mixture with suitable carrier. Proposes (R)-2-arylpropionic acid omega-alkylamides are useful for inhibition of hemotaxic activation induced C5a and other hemotaxic proteins.

EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.

18 cl, 3 tbl, 23 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to methods for preparing N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine (nateglinide). Method for preparing nateglinide crystals of H-type is carried out by addition of inorganic acid to reaction mixture containing nateglinide to provide its acidification. The reaction mixture is prepared by interaction of trans-4-isopropylcyclohexylcarbonyl chloride with D-phenylalanine in a mixed solvent consisting of a ketone solvent and water in the presence of alkali. The ratio of water to ketone solvent is from 10:1 to 0.5:1. Temperature of the mixture is brought about to 58-72°C and concentration of ketone solvent - up to value above 8 wt.-% and less 22 wt.-% for carrying out precipitation of nateglinide crystals. Invention proposes variant for preparing nateglinide crystals of H-type. Also, invention proposes crystals of nateglinide of H-type showing average value of longitudinal axis from 1 to 5 mm and that for transverse axis from 0.1 to 0.5 mm. Invention provides enhancing effectiveness in isolation of nateglinide crystals.

EFFECT: improved preparing methods.

10 cl, 1 tbl, 13 ex

FIELD: industrial organic synthesis.

SUBSTANCE: invention provides a simple method for preparing high-purity acylphenylalanine useful as starting material for pharmaceutical products. Process comprises Schotten-Bauman reaction stage wherein acid chloride reacts with phenylalanine in mixed solvent consisting of water-miscible organic solvent and water, while maintaining alkali pH (>10) of solvent medium with the aid of potassium hydroxide.

EFFECT: prevented formation of impurities.

13 cl, 4 tbl, 12 ex

FIELD: organic chemistry, detergents.

SUBSTANCE: claimed method includes interaction of ethylene diamine with tetraacetic acid. Obtained reaction mixture is treated with acetic anhydride at elevated temperature and N,N,N',N'-tetraacetylethylene diamine is isolated from reaction mass by crystallization. Reagent interaction is carried out in system of two continuous reactors acting in mixing-displacement regime at continuous raw material feeding such as ethylene diamine into top of the first reactor and acetic anhydride into top of the second reactor. Molar ratio of fresh acetic anhydride to ethylene diamine is 2.05-2.1. Temperature difference between top and bottom parts is maintained from 20 to 30°C for the first reactor and from 20 to 40°C for the second one. Compound of present invention is useful in detergent compositions.

EFFECT: target product of increased yield and purity, simplified process.

1 dwg, 1 tbl, 8 ex

FIELD: industrial organic synthesis.

SUBSTANCE: process involves formic acid-methylamine reaction via intermediate methylammonium formate salt, which is dehydrated in presence of molybdenum trioxide catalyst dissolved in aqueous methylamine and added to formic acid in amount 2.0-4.0 wt % based on the latter. Reaction is carried out for 1-2 h in reactor filled with inert packing material having developed surface without cooling of reaction mixture, whereupon volatile products are distilled away at bottom temperature up to 190°C for 60-90 min. Bottom residue containing catalyst, after isolation of desired product, is returned to reactor.

EFFECT: reduced reaction time, reduced power consumption, improved quality of product obtained at increased yield, and diminished production waste.

5 cl, 8 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of aromatic carboxylic acid aminoanilides, such as 21-chloro-4,41-diaminobenzanilide or bis-(2-chloro-4-aminophenol)terephthalamide used in production of thermostable, refractory and highly strength fibers. Method is carried out by acylation of 2-chloro-4-nitroaniline with 4-nitrobenzoic acid chloroanhydride or terephthaloyl chloride, respectively, in organic solvent medium at heating followed by reduction of formed chloro-substituted nitroanilide of aromatic carboxylic acid in a solvent. The acylation process is carried out in the presence of ferric chloride as a catalyst, at chloroanhydride excess with respect to 2-chloro-4-nitroaniline at graduate increase of temperature up to boiling of reaction mass under atmosphere pressure. Ferric chloride is used as anhydrous FeCl3 or crystal hydrate FeCl3 x 6H2O or an aqueous solution. In the reduction process a mixture of water and dipolar aprotonic solvent is used, and mother solutions after isolation of chloro-substituted nitroanilide and chloro-substituted aminoanilide are recovered to recycle at corresponding step of process. Before recovering to recycle at acylation or reduction step, respectively, mother solutions are treated with activated carbon. Invention provides preparing end products of high quality and decreasing amount of waste.

EFFECT: improved method of synthesis.

6 cl, 1 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: method to manufacture benzyldimethyl[3-(myristoilamino)propyl]ammonium chloride monohydrate-С26Н47ClN2О·Н2О implies two stages, which are reacting myristic acid followed by the end product formation at the second stage. 3-dimethylaminopropylamide is obtained at the first stage by direct reaction of myristic acid with 3-dimethylaminopropylamine in aromatic hydrocarbons, while end product is obtained at the second stage by direct benzylation in alcohols or ketones.

EFFECT: improved purity of end product and process safety.

3 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the optically active compounds of bisoxazoline of the formula (1) and the method of their preparation, to the new intermediate products and methods of their preparation, it also refers to cooper asymmetric complex on the basis of the bisoxazoline optically active compound of the formula (1) and the method of preparation of cyclopropalcarbon acids using the asymmetric complex. In the compound of the formula (1) , R1 and R2 are equal and each time stand for C1-6 alkoxy group, C1-6 alkyl group substituted by unsubstituted phenyl group or phenyl group substituted by C1-6 alkyl or C1-6 alkoxy group, R1 and R2 with carbon atom of oxazoline ring, to which they are joined and form cykloalkyl ring which has 3-7 carbon atoms, R3 defines unsubstituted 1-naphthyl group or 2-naphthyl group, or 1-naphthyl group or 2-naphthyl group substituted by at least one C1-6 alkyl group or C1-6 alkoxy group; R4 and R5 are equal and each of them stands for hydrogen atom or C1-6 alkyl group or R4 and R5 with carbon atom, to which they are joined, form cykloalkyl ring which has 3-6 carbon atom and * mean asymmetrical center.

EFFECT: usage of the asymmetrical complex allows getting cyclopropanecarboxylic acid in high yields.

16 cl, 11 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to the method of making compounds with formula , involving reaction of but-2-enoic acid with chlorotrimethylsilane, bromination of the obtained trimethylsilylcrotonate with N-bromosuccinimide, reaction of the obtained trimethylsilyl-4-bromocrotonate or methyl or ethyl 4-bromocrotonate with dimethylamine so as to obtain 4-dimethylaminocrotonic acid, its separation in form of hydrochloride and chlorination with oxalyl chloride. The method allows for obtaining 4-dimethylamino-2-butenoylchloride, suitable for use as an intermediate compound in the synthesis of pharmaceutically active protein kinase inhibitors.

EFFECT: obtaining the agent, suitable for use as an intermediate compound in the synthesis of pharmaceutically active protein kinase inhibitors.

1 cl, 2 dwg, 3 ex

FIELD: chemistry; food products.

SUBSTANCE: present invention relates to use of N-isobutylamide 2E,4E-decadienoic acid (trans-pellitorine) as an aromatic substance, with a sialagogue but not burning effect in compositions used for food, oral hygiene or consumed for delectation, where trans-pellitorine is used in amounts of 20 parts/million in terms of the total mass of the composition. The invention also relates to the aromatic composition, with a sialagogue but not burning effect, containing trans-pellitorine in amounts of 20 parts/million in terms of the total mass of the composition, as well as to the method of obtaining trans-pellitorine. The invention also pertains to the method of obtaining N-isobutylamide 2E,4E-decadienoic acid.

EFFECT: obtaining a substance with sialagogue and/or irritant effect, as well as a wide neutral aromatic profile.

6 cl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes acylated 6,7,8,9-tetrahydro-5H-benzocycloheptenylamines of the general formula (I): wherein R1 and R4 mean independently hydrogen atom (H), (C1-C10)-alkyl monosubstituted with fluorine atom (F); R2 and R3 mean independently H and (C1-C10)-alkyl; A means -CH, -CHOH; each among B, C and D means -CH2; R5 means possibly substituted phenyl or group Hetar. Also, invention describes method for synthesis of indicated compounds and a pharmaceutical preparation designated for stimulation of expression of endothelial NO-synthase. Nitrogen oxide (NO) released by endothelial tissue displays important significance in function of some main mechanisms of cardiovascular system. Nitrogen oxide exerts the vasodilating effect and inhibits platelets aggregation, adhesion of leukocytes to endothelial tissue and proliferation of smooth muscle cells in internal envelope of blood vessels.

EFFECT: valuable medicinal properties of compounds and pharmaceutical preparations.

16 cl, 1 tbl, 152 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds -acidified arylcycloalkylamins of formula I in any of their stereoisomeric forms or in form of their mixture in any ratio, or their pharmaceutically acceptable salts, where in formula I : R1 represents aryl, not obligatory substituted with one or two similar or different substitutes, selected from group that includes C1-C6-alkyl and halogen; R2 represents aryl or heteroaryl, which represents residue of 5-6-member aromatic monocyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom and/or 1 sulfur atom or oxygen atom, or residue of 9-10-member aromatic bicyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom, each of which is unsubstituted or contains 1-3 similar or different substitutes, selected from group, consisting of halogens, NH2, unsubstituted C1-C10-alkyl, C1-C10 -alcoxy, C1-C10-alkylamino and di(C1-C10-alkyl)amino, and at least monosubstituted C1-C10-alkyl, etc., n represents 1, 2, 3 or 4. Invention relates to pharmaceutical composition, stimulating expression of endothelial NO synthase, based on said compounds, as well as application of compounds of formula I for production of medication for stimulating expression of endothelial NO-synthase and for treatment of such cardiovascular diseases as atherosclerosis, thrombosis, coronary artery disease, hypertension and impaired cardiac function.

EFFECT: invention ensures enhancing composition and treatment method efficiency.

9 cl, 2 tbl, 41 ex

Up!