The method of obtaining benzamide
(57) Abstract:The inventive product-benzamid, so pl. 128-129°C. Reagent 1: methyl ester of benzoic acid. Reagent 2: NH3in CH3OH . Reaction conditions: in the presence of water at a mass ratio of methyl ester of benzoic acid: CH3OH in NH3aq. 25% 1:(5-10):(4,5-7) mainly at room temperature. 1 C.p. f-crystals, 1 table. The invention relates to chemistry, specifically to an improved method of obtaining benzamide.Known methods for producing benzamide of the methyl ester of benzoic acid interaction with ammonia in the presence of a catalyst of the type of aluminum chloride [Japan's Bid 79 76501, class C 07 C 103/00] or with a large excess of ammonia at temperatures above 100aboutWith pressure [Dormidontova N. In., Ustavshikov B. F., farberow M. I., scientific notes Yaroslavl Institute of technology, 1971, T. 22, vol.1, pp. 77-82. The reaction rate of the ammonolysis of esters of a-hydroxy acids and their correlation equation taffeta].Known methods for producing benzamide of the ethyl ester of benzoic acid by contact with an aqueous ammonia when heated to 100about[ompt. rend. Acad. Sci., 1847, v.25, p.734] or when heated with alcoholic ammonia; the closer the proposed method is a method of obtaining benzamide, it lies in the fact that the ethyl ester of benzoic acid is subjected to interaction with ammonia in a solution of methanol in the presence of a catalyst. As catalyst using sodium cyanide. In a closed vessel at 50aboutWith exposure to 50 h, the conversion of ether was 79% and the actual yield of 64% . In the absence of sodium cyanide conversion does not exceed 57% [Hogberg , T., Strom, P., Ebner, M., Ransby, S., J. Org. Chem., 1987, v.52, N 10, p.2033-2036, Cyanide as an Efficient and Mild Cataiyst in the Aminolysis of Esters] (prototype).The disadvantage of the prototype method is the low yield of the target product and the use of toxic catalyst.The aim of the invention is to simplify the process, improve its environmental safety and increase the yield of the target product. This goal is achieved by a method of obtaining benzamide, which consists in the fact that the methyl ester of benzoic acid is subjected to interaction with ammonia in aqueous methanol in the presence of a catalyst, which in this way is water at the weight ratio of methyl ester of benzoic acid:methanol:aqueous ammonia (25%) 1:(5-10):(4,5-7), usually at room temperature.For separation of the target product, it is advisable to remove the excessive number of Ada with the addition of a small amount of ammonia.Thus, in the proposed method all unreacted reagents can be regenerated and used in subsequent cycles. Therefore, the proposed method is environmentally safe.Although the amidation of esters of carboxylic acids is a common method of obtaining amides in organic chemistry repeatedly attempts were carried out its application to the esters of benzoic acid, low reaction rate and reversibility of the processes are not allowed to rely on its practical implementation for the synthesis of benzamide. This is illustrated by the work of Gordon and co-authors (Gordon M. , Miller J. G., Day, A. R. J. Am. Chem. Soc., 1948, v.70, No. 5, p. 1946-1953. Effect of structure on reactivity. I.; Gordon M., Miller J. G., Day, A. R. ibid., 1949, v.71, No. 4, p.1245-1250. ibid. II.) to study the kinetics of different ammonolysis of esters. Unlike esters of fatty acids of a number of esters of aromatic acids, in particular benzoic acid, are virtually inert in the reactions of ammonolysis. In the same conditions, the relative speed of the ammonolysis of methylbenzoate is only 8% of the speed of ammonolysis of methyl acetate (PL. 6, Gordon M., Miller J. G., Day, A. R. ibid., 1949, v.71, No. 4, p.1245-1250. Effect of structure on reactivity. II.)
The comparison of the velocities of the ammonolysis of esters of benzoic acid shows that alcohol residue is.R. ibid. , 1949, v.71, No. 4, p.1245-1250. Effect of structure on reactivity. II.)
Emil Femera [Fischer E., Dilthey, A., Ber., 1902, B. 35 (I), N 3, S. 844-856. Einwirkung von Ammiak auf die Alkylmalonester.] it is shown that for hours in the heat of ethylbenzoic with a large excess saturated at 0aboutWith alcoholic ammonia at 25aboutWith leads to the formation of benzamide with 5%, and at 175aboutWith only 1.7%. In effect described the positive effect of the proposed method is unexpected, and the way to obtain benzamide by ammonolysis of methylbenzoate in aqueous ammonia at room temperature could not be offered a priori.Selection of optimal process conditions unexpectedly allowed to get benzamid with high yield and high quality environmentally friendly and essentially waste-free way.At the stage of ammonolysis temperature increase process certainly increases the speed of ammonolysis, however, even more significantly increased rate of adverse reactions and to obtain the pure target product is not immediately successful, and additional procedures are required to clean it.Increasing the amount of ammonia increases output benzamide, however, to maintain the reaction mixture homogeneous prihodilo process.Distinctive features of the proposed method are used as initial compounds methyl ester benzoic acid, as a catalyst of water at a mass ratio of benzoic acid: methanol:aqueous ammonia (25%) 1:(5-10):(4,5-7).P R I m e R s 1-9. To the methyl ester of benzoic acid added 25% aqueous solution of ammonia and methyl alcohol in an amount necessary for the formation of a homogeneous reaction mass. The mixture was kept at room temperature for a period specified in the time table. Ammonia and methanol removed unreacted methylbenzoate is distilled off with steam up until the distillate will not become completely transparent. Upon cooling, benzamid crystallizes. Receive benzoic acid amide with so pl. 128-129aboutC. 1. The METHOD of OBTAINING BENZAMIDE interaction Olkiluoto ester of benzoic acid with a solution of ammonia in methanol in the presence of a catalyst, characterized in that as Olkiluoto ether use methyl ester benzoic acid, and the catalyst - water at a mass ratio of methyl ester of benzoic acid : methanol : aqueous ammonia(25%) 1 : 5 - 10 : 4,5 - 7 respectively.2. JV
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
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
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
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
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
SUBSTANCE: invention relates to the compounds of the formula and their pharmaceutically acceptable salts used as inhibiting agent in the relation of fermentative beta-secretase and it also relates to pharmaceutical compositions based on the formula. In general formula one of RN and RN' represents hydrogen, and another represents - C(=O)-(CRR')0-6R100, or where R4 is chosen from the group including H; NH2; -NR50CO2R51; -(C1-C4)-alkyl-NR50CO2R51; where n7 is equal to 0, 1, 2 or 3; R50 represents H or C1-C6alkyl; R51 is chosen from the group including phenyl-(C1-C4)-alkyl and (C1-C6)-alkyl; X is chosen from the group including -(C1-C6)-alkylidenyl optionally substituted with 1, 2 or 3 metal groups; Z is chosen from the group including bond, SO2, SO and S; Y stands for (C1-C10)-alkyl; R1 represents -(C1-C6)-alkylphenyl where phenyl ring is optionally substituted by 1, 2, 3 or 4 halogen atoms; R and R' independently represent hydrogen or (C1-C6)-alkyl; R2 represents hydrogen; R3 represents hydrogen; Rc represents - (CR245R250)0-4-aryl; where aryl is optionally substituted by 1, 2 or 3 R200; R200 is chosen from the group including (C1-C6)-alkyl optionally substituted with 1, 2 or 3 groups R205; halogen; C=N; R205 stands for halogen; R245 and R250 in each case stands for H; either R245 or R250 are taken together with carbon atom whereto attached to form carbocycle from 3, 4, 5, 6 or 7 carbon atoms; R100 represents 5-6-merous heteroaryl with 1-2 heteroatoms chosen from nitrogen and sulphur, -phenyl-W-heteroaryl where heteroaryl is 5-6-merous ring containing 1-2 heteroatoms, chosen from nitrogen and oxygen and where cyclic parts of each group are optionally substituted by 1, 2 or 3 groups independently chosen among C1-C6alkyl, -(CH2)0-4-CO2-NR105R'105, -(CH2)0-4-SO2-NR105R'105, -(CH2)0-4-N(R150)-CO-R105, -(CH2)0-4-N(R150)-SO2-R105; W represents -(CH2)0-4; R105 and R'105 independently represent (C1-C6)-alkyl optionally substituted with -NH2 or halogen; R150 represents hydrogen.
EFFECT: compounds can be applied to prevent and treat diseases mediated by excess activity of beta-secretase such as Alzheimer's disease.
11 cl, 12 tbl, 3 dwg, 1729 ex
SUBSTANCE: present invention relates to novel compounds of formula I: ,
to their synthesis method, a pharmaceutical composition based on said compounds and use of said compounds in making medicinal agents. Substitutes R1, R2, R4, R5, as well as values of A, B, D and n are given in the formula of invention.
EFFECT: obtaining novel compounds of formula I: ,
as well as their pharmaceutically acceptable salts which have inhibitory effect on cholesteryl ester transfer protein (CETP).
14 cl, 251 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a new chemical compound - N-1-[(4-fluorophenyl)-2-(1-ethyl-4-piperidyl)-ethyl]-4-nitrobenzamide hydrochloride of formula Also, the invention refers to drugs.
EFFECT: preparation of a new biologically active compound which exhibits antiarhythmic and antifibrillatory activity.
2 cl, 1 ex, 2 tbl
SUBSTANCE: present invention relates to hot or sweet flavourants in form of a synthetic amide compound or edible salt thereof in amount ranging from approximately 0.001 parts per million to approximately 100 parts per million. The amide compound has formula
where A is a phenyl or a 5- or 6-member heteroaryl ring selected from a group comprising pyridine, pyrazine, pyrazole, thiazole, furan, thiophene, benzofuran and benzothiophene; m equals 1, 2 or 3, each R1 is independently selected from hydroxyl, fluorine, chlorine, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy and isopropoxy, or alternatively two R1 are bonded to form a saturated C1-C3 alkylenedioxy ring on the phenyl; and R2 is a C3-C10 branched alkyl. The amide compound also has formula
in which substitutes A, B, R50, R60, R70, R80, n and m assume values given in the formula of invention. The amide compound is also a specific chemical compound.
EFFECT: obtaining hot and sweet taste modifiers and boosters for food and medicinal products.
39 cl, 7 tbl, 180 ex
SUBSTANCE: invention relates to a novel method of producing terephthalic acid diamide, which can be used in synthesis of polymers, involving reaction of terephthalic acid and urea in stoichiometric ratio, wherein reaction of initial reagents is carried out in solid phase with thorough mixing and simultaneous grinding, at temperature 180-240°C and pressure created by urea decomposition products equal to 5-15 kg/cm2 for a time defined from the beginning of the reaction, specifically from the moment given temperature and pressure values are achieved to the moment of spontaneous fall of the reaction pressure, and then holding the reaction mixture for 1-3 hours.
EFFECT: simple, single-step method without use of aggressive reagents, characterised by high output of high-quality diamide and no formation of additional wastes.
1 cl, 7 ex
SUBSTANCE: invention relates to a novel method of producing terephthalic acid diamide which can be used in production of polymers, involving reaction of terephthalic acid with ammonia, wherein the reaction takes place in a fluidised bed at atmospheric pressure, first at temperature (75-80)°C and ratio acid: gaseous ammonia equal to 1:2-5, while feeding ammonia in amount of 22.05-410.3 l/h and carrying out the reaction for 1.0-2.5 hours until formation of a diammonium salt of terephthalic acid, and then at temperature 240-260°C and ammonia flowrate of 2-5 l/h, while feeding nitrogen in an amount which is sufficient to maintain the fluidised bed and carrying out the reaction for 2-4 hours until release of water ceases.
EFFECT: creating an environmentally safe method by avoiding the need to use volatile reactants, which ensures high output (95-98%) and high quality of the end product.
1 cl, 7 ex