The method of obtaining organic azides

 

The way to obtain azide derived organic compounds according to the invention involves attaching azide function to the organic compound via reaction of epoxy-derived organic compounds and azide salt of an alkali metal in a solvent. Before and/or during the reaction, to the reaction mixture (1-6C)alkilany ether (2-4C)carboxylic acid having a boiling point above the reaction temperature, the amount close to equimolar relative to the epoxy derivative. Epoxy derived organic compounds selected from styrene oxide, 2,3-epoxybutane, indene oxide and epoxy derived carbohydrate. The reaction temperature is between 60 and 120C. the Technical result - the reduction of by-products, reduction of corrosion of the enamel coating of the reactor. 6 C.p. f-crystals, 1 tab., 2 Il.

The invention relates to a method of joining azide function to an organic compound. In such a way to obtain the azide derivative of an organic epoxy compounds derived organic compounds and azide salt of an alkali metal is introduced into the reaction in plants the stage of synthesis of compounds with amino groups, the introduction of the azide group can be accomplished either by substitution by azide appropriate leaving groups, such as toilet, mesilate or chloride, or attach azide anion to the epoxide. For example, zidovudine, potential precursors of 1,2-aminoalcohols can be derived from epoxides by reaction with an azide of an alkali metal under alkaline or acidic conditions.

In most known in the field of methods to attach the azide to the epoxide process is carried out in a polar organic solvent at a temperature of about 100-110°C, in combination with a buffer system, such as ammoniacal, ammoniumsulfate or three-isopropylbenzenesulfonyl acid/2,6-lutidine (Van Boeckel et al., J. Carbohydr. Chem., 1985, 4, 293-321). The problems faced in such ways that are adverse reactions that can occur in acidic or alkaline conditions, leading to isomerization, epimerization and rearrangement. An additional serious disadvantage of the use of ammonium salts are education ammonium azide, which is an explosive compound, and the use of ammonium chloride to the epoxide instead azide can also join chloride. The use of buffers, consisting of a mixture of the lots, representing a highly toxic and explosive gas. In the General case of the reaction with aside alkali metals cannot be carried out in reactors made of stainless steel, because there is the possibility that upon contact with the reactor walls will form azides of heavy metals, such as azides chromium or Nickel. Such azides of heavy metals in dry form are explosive. In addition, azide ion has the same corrosive properties, such as chloride ion or bromide. On the other hand, in reactors with enamel-coated at temperatures of 100-110°may also cause serious corrosion of the enamel coating. In particular, this occurs under alkaline conditions, when, for example, with the use of sodium azide in water and dimethylformamide pH may increase to values above 12 because of the formation of sodium hydroxide.

Now discovered that it is possible to avoid one or more of the above-mentioned disadvantages of the known methods of joining azide function to the organic compound, if before and/or during the reaction, to the reaction mixture is added to compound (1-6C)alkilany ether (2-4C)carboxylic acid having a boiling point above the reaction temperature in kolichestvo branched alkyl group, having 1-6 carbon atoms and (2-4C)carboxylic acid refers to a straight or branched carboxylic acid having 2-4 carbon atoms.

The presence of such ether in the reaction mixture maintains the pH during the formation of organic azide in an acceptable interval. Ester its shades hydroxide ions formed during the reaction and, thus, the pH is maintained below 10. When using this procedure, the reaction accession azide can be conducted safely in the reactor enamel without education attestovannoi acid and without corrosion of the enamel layer of the wall of the reactor.

Can be used esters which have a boiling point above the reaction temperature. The boiling point should be above this temperature, otherwise the ester will evaporate from the reaction mixture. Examples of suitable esters are (1-6C)alkylphosphate, (1-5C)allylacetate, (1-4C)alkylphosphonate, (1-3C)alkylsulfonate, with butyl acetate is preferred.

The reaction mixture is heated to the reaction temperature at which the epoxy derivative and azide can react with the formation of the azide derived organic compounds. About the as long until the reaction is complete.

The molar ratio between the added amount of ester and added amount of epoxide in the reaction time should be close to equimolar relative to the epoxy derivative. Usually close to equimolar ratio is within the range from 0.9 to 1.1. A ratio of 1.0 is preferred. A ratio of less than 0.9 ultimately may allow the pH to reach values of more than 12, with negative consequences for the enamel coating of the reactor, and the ratio of more than 1.1 may lead to the formation of alanovoy acid, with which the alkali metal azide can give volatile, toxic and explosive attestation acid.

Ester may be added to the reaction mixture before the reaction or during the reaction or at the same time and before and during the reaction, although from a practical point of view it is preferable to add the ester before the beginning of the reaction.

The method of this invention can be used to obtain the azide derivative adjacent to the hydroxyl function of any organic compound capable of epoksidnogo function. Examples of organic compounds bearing an epoxy function for this is s are derivatives of carbohydrates with an epoxy function. It is more preferable to use in this process, epoxy derivatives of 1,6:2,3-dianhydro-4-O-phenylmethyl-D-mannopyranose or 1,6: 2,3-dianhydro-4-O-[2,3-bis-O-phenylmethyl-4,6-O-phenylmethylene-D-glyukopiranozil]--D-mannopyranose or 1,6:2,3-dianhydro-4-O-[2,3-bis-O-phenylmethyl-4,6-O-(1-methylethylidene)--D-glyukopiranozil]--D-mannopyranose. Additionally, the preferred application of the method is to obtain 2-azide-2-deoxy-pyranose, which is the precursor glycosamino fragment in glycosaminoglycan with antithrombotic properties.

Aside alkali metals that may be used are lithium azide, potassium azide and sodium azide, while preferred is sodium azide.

The method can be used many different types of solvents such as ethanol, acetonitrile, dimethylsulfoxide or hexamethylene. It is preferable to use a polar aprotic solvent which is a solvent miscible with water, has a high dielectric constant (>15) and not capable DVD, M-methylpyrrolidone or dimethylacetamide. N-methylpyrrolidinone is the most preferable when atidaryta carbohydrates. Preferably the solvent, water is added in order to achieve a higher concentration of water-soluble alkali metal azide in the reaction mixture. In the reaction mixture may contain a large amount of water, up to an equal volume of organic solvent.

The reaction accession can usually held at the reaction temperature varying in the range of 60 to 120°C, and preferably at 110°C.

Completion of the reactions of addition can be determined by measuring concentration of components in a mixture by methods well-known to specialists in this field. The reaction can last from one hour to several days, depending on the reactivity of organic epoxide and the various compounds in the mixture. When there is no significant increase in the number of organic azide formed during the reaction, or the number of products undesirable side reactions increases, the reaction was completed.

The following example is described to illustrate the invention.

Captions to figures.

Figure 1: Reaction s 2: Reaction scheme of merger azide functions the following epoxides: 1,6:2,3-dianhydro-4-0-[2,3-bis-O-phenylmethyl-4,6-O-phenylmethylene-D-glyukopiranozil]--D-mannopyranose, 1,6:2,3-dianhydro-4-O-[2,3-bis-O-phenylmethyl-4,6-O-(1-methylethylidene)--D-glyukopiranozil]--D-mannopyranose, cyclohexanone, glycidylmethacrylate ether, styrene oxide and the oxide of indene.

Example

The procedure of joining azide to 1,6:2,3-dianhydro-4-0-phenylmethyl-D-mannopyranose.

10,88 kg 1,6:2,3-dianhydro-4-O-phenylmethyl-D-mannopyranose (1 in figure 1) was dissolved in 54,4 l 1-methyl-2-pyrrolidone in the reactor enamel. Added 6113 ml n-butyl acetate, 9028 g of sodium azide and 38 liters of water. The mixture was heated at 100-110°C and was stirred for 20 hours at l00-110°C. the Mixture was cooled to 25°C and was added water and ethyl acetate. The product was separated from the reaction mixture by extraction with ethyl acetate.

An ethyl acetate extract was evaporated at 60°C in vacuum with the introduction of water and the product was led out of the water at 30°C.

After filtration, washing and drying the yield was $ 11,935 kg 1,6-anhydrous-2-azido-4-O-phenylmethyl-2-deoxy--D-glucopyranose (2 on figure 1).

TLC: toluene/ethyl acetate 70/30 RF:0,35; temperaturein to TMS standard at 0 MD in the table.

This reaction was carried out with the following epoxides according to the method described above:

With 1,6:2,3-dianhydro-4-O-[2,3-bis-O-phenylmethyl-4,6-O-phenylmethylene-D-glyukopiranozil]--D-mannopyranose (3 on figure 2) obtaining 1,6-anhydrous-2-azido-4-O-[2,3-bis-O-phenylmethyl-4,6-O-phenylmethylene-D-glyukopiranozil]-2-deoxy--D-glucopyranose (4 on figure 2). TLC: toluene/ethyl acetate 70/30 on the silicon dioxide, RF:0,42.

With 1,6:2,3-dianhydro-4-O-[2,3-bis-O-phenylmethyl-4,6-O-(1-methylethylidene)--D-glyukopiranozil]--D-mannopyranose (5 on figure 2) obtaining 1,6-anhydrous-2-azido-4-O-[2,3-bis-O-phenylmethyl-4,6-O-(1-methylethylidene)--D-glyukopiranozil]-2-deoxy--D-glucopyranose (6 in figure 2). TLC: dichloromethane/acetone 90/10, RF:0,50.

With cyclohexanethiol (7 in figure 2) to obtain 2-acidalkaline (8 in figure 2). TLC: dichloromethane/methanol 60/40, RF:0,93.

With glycidylmethacrylate ether (9 in figure 2) to produce according to NMR mixture of 9:1 3-azido-2-hydroxypropyl isopropyl is 75.

With styrene oxide (12 in figure 2) to obtain according to the NMR of the mixture 1:1 2 azido-1-phenylethanol (13 in figure 2) and 2-azido-2-phenylethanol (14 in figure 2). TLC: dichloromethane/methanol 60/40, RF:0,90.

With indene oxide (15 in figure 2) to produce according to NMR 2-asiaindian-1-ol (16 in figure 2) and/or 1-asiaindian-2-ol (17 in figure 2). TLC: toluene/ethyl acetate 1/1, RF:0,74.

Claims

1. The way to obtain azide derived organic compounds, including the accession of the azide function to an organic compound in which an epoxy derived organic compounds and azide salt of an alkali metal is introduced into the reaction in a solvent, characterized in that before and/or during the reaction, to the reaction mixture (1-6C)alkilany ether (2-4C)carboxylic acid having a boiling point above the reaction temperature, the amount close to equimolar relative to the epoxy derivative.

2. The method according to p. 1, characterized in that the epoxy-derived organic compounds selected from styrene oxide, 2,3-epoxybutane, indene oxide and epoxy derived carbohydrate.

3. The method according to p. 2, characterized in that the epoxy-derived organic soedineniya is 1,6:2,3-dianhydro-4-O-phenylmethyl-in-D-mannopyranose or 1,6:2,3-dianhydro-4-O-[2,3-bis-O-phenylmethyl-4,6-O-phenylmethylene-in-D-glyukopiranozil]-b-D-mannopyranose, or 1,6:2,3-dianhydro-4-O-[2,3-bis-O-phenyl-methyl-4,6-O-(1-methylethylidene)-b-D-glyukopiranozil]-b-D-mannopyranose.

5. The method according to any of paragraphs.1-4, characterized in that the reaction temperature is between 60 and 120C.

6. The method according to any of paragraphs.1-5, characterized in that the ester is butyl acetate.

7. The method according to any of paragraphs.1-6, characterized in that the reaction mixture are added water in an amount at most equal to the volume of solvent.



 

Same patents:

The invention relates to methods for diacetone-L - sorbose used in the production of ascorbic acid

The invention relates to methods for DAS used as an intermediate product in the production of ascorbic acid (vitamin C)

The invention relates to new derivatives of fatty acids, which drugs or agrochemicals, with improved performance as it relates to lipophilic derivative of biologically active compounds of the General formula CH3-(CH2)7-CH=CH-(CH2)n-X -, where n is an integer of 7 or 9; X is selected from the group comprising-COO-, -CONH-, -CH2O-, -CH2S-, -CH2O-CO-, -CH2NHCO-, -COS-; lipophilic group SN3-(CH2)7-CH=CH-(CH2)n-X - is CIS - or transconfiguration; And is a fragment of a molecule of biologically active compounds (BAC), non-nucleoside and nucleoside derivative and containing in its structure at least one of functional groups selected from a) alcohol, b) simple broadcast) phenol, (d) amino, (e) thiol, (f) carboxylic acids and (g) of ester carboxylic acid, provided that no connection specified in paragraph 1 of the claims

The invention relates to N-allyl-D-glucosamine formula (1) as adaptogene

The invention relates to the field of organic chemistry and can find application in biology and medicine

The invention relates to the field of organic chemistry and relates to the process of obtaining intermediate for the synthesis of vitamin B2

The invention relates to compounds that are used as medicines, which have antiendotoxin activity, in particular analogs of lipid A

The invention relates to new compounds of the number of semicarbazides, namely 4-(glucopyranosyl) semicarbazides General formula

R-NH-CO-NH-NH2(I) where R = D-glucosyl-D-galactosyl-L-arabinosyl-that can be used for the synthesis of compounds possessing anti-inflammatory, antimicrobial activity

The invention relates to hexanitrohexaazaisowurtzitane and method thereof

The invention relates to the field management of chemical engineering processes and relates, in particular, the automation of the processes of preparation of solutions of initial components in semi-continuous reactors actions (CND) for the subsequent synthesis of the desired products, which find wide application in paint and chemical-pharmaceutical industries upon receipt of varnishes, paints, medicines and vitamins

FIELD: molecular biology, bioorganic chemistry.

SUBSTANCE: method for preparing DNA-chip involves modifying a polymer surface comprising electrophilic groups with compound of the formula: H2N-X-Si(OR)3 wherein X means propyl; R means ethyl in gaseous phase, and with a solution of compound of the formula: Y-X-Si(OR)3 wherein Y means a functional group; X means propyl; R means ethyl or methyl. Then oligonucleotide is immobilized on the modified surface of a polymer by the covalent route. Use of the invention provides decreasing the cost and enhancing effectiveness of modification of backing in production of DNA-chips.

EFFECT: improved preparing method.

11 cl, 10 dwg, 2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: disclosed is a method of producing surface-modified nanoparticles for immobilising biological substances. The method involves modifying Fe3O4 nanoparticles containing ester groups. The obtained particles are then treated with aminopropyl triethoxy silane. Further, the suspension of nanoparticles is incubated with a condensing agent and the enzyme is immobilised.

EFFECT: method enables to obtain immobilised preparations with high enzyme specific activity.

3 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I , isomer thereof of formula IA , mixture of isomers thereof IA/C , synthesis method thereof, as well as methods of producing compounds of formula IVA from compounds of formula IA, involving reduction and removal of protection from compounds of formula IA via hydrogenolysis using H2 and a catalytic amount of Pd/C, in the presence of trifluoroacetic acid to obtain a compound of formula VA; further reaction of this compound with Cbz-t-leu-OH, EDC and HOBt to obtain a compound of formula VIA; reaction of compound VIA with H2 and a catalytic amount of Pd/C in the presence of citric acid to obtain an amine and reaction of said amine and 4-amino-3-chlorobenzoic acid in the presence of CDMT and NMM to obtain a compound of formula IVA.

EFFECT: fewer synthesis steps and high output while using dynamic crystallisation.

13 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the technique for nitration of aromatic compounds, and specifically to a method for catalytic nitration of aromatic compounds with nitric acid in a column-type apparatus. The apparatus is simultaneously a reactor and a fractionation column and is filled with a catalytically active filling consisting of a carrier on which an active component is deposited. The catalytically active filling used has ratio of the mass of the active component to the volume of the catalyst of about 0.4 g/cm3, with the amount of the active component - sulphated titanium or zirconium oxides of 5-20% of the mass of the catalyst.

EFFECT: invention provides high rate of nitration without using excess nitric acid, reduces output of byproducts and improves isomeric composition of products.

3 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: relates to field of obtaining N-nitrosodialkylamines. Method of obtaining N-nitrosodialkylamines consists in interaction of water solutions of dialkylamines with carbon dioxide with molar ratio of dialkylamine to carbon dioxide (12):1 with further processing of carnonates of dialkylamines with gas mixture of nitrogen with equimolecular mixture of nitrogen oxide and dioxide or gas mixture of nitrogen with nitrous anhydrite with molar ratio of dialkylamine to nitrogen oxides, in terms of nitrous anhydrite, not less than 1:1, reaction mass being kept at temperature 30-60C, with support of pH of reaction mixtures 3-6.5 for 15-60 minutes.

EFFECT: invention makes it possible to reduce energy consumption, ensure ecological safety of technological production, with simultaneous increase of end product.

1 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and (II), a method for production thereof, metal-containing catalyst systems based on said compounds and a method for hydrocyanation in the presence of said catalyst systems. Compounds of formulae (I) and (II): where R1, R2, R3, R4, R6 and R7 denote H, C1-C12alkyl, an aromatic or cycloaliphatic ring, a carbonyl, alkoxycarbonyl or alkoxy radical, a halogen atom, a nitrile or haloalkyl group containing 1-12 carbon atoms, R5 and R8 denote an aliphatic radical containing 1-12 carbon atoms, an aromatic or cycloaliphatic ring, or multiple aromatic rings which are condensed or bonded with each other.

EFFECT: novel method of producing novel compounds and a catalyst system of formula M[Lf]t, where M denotes a transition metal, Lf denotes an organophosphorus ligand of formula (I) or (II), t is a number from 1 to 10, which can be used in a novel method for hydrocyanation of hydrocarbons.

14 cl, 12 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to catalytic systems based on organophosphorous compounds, complex-forming, suitable for hydrocyanation and hydroformylation of alkenes of formulas M[Lf]t(V) or HM[Lf]t+nCO4-n(VI), where M is transition metal, t is number from 1 to 10, n is number from 1 to 4, Lf stands for organofosphorous ligand of formulas:

or ,

where R1, R2, R3, R4, R5, R7, Z stand for hydrogen atom, C1-12alkyl, phenyl, optionally substituted with 1-3 substituents, selected from C1-6-alkyl and hydroxy-C1-6-alkyl, or C1-12halogenalkyl; X, X1 and X2 stand for O or S, R6 stands for covalent bond, C6-aryl or several bound C6-aromatic cycles, n and n1, stand for valence X1, X2, reduced by 2.

EFFECT: claimed are novel effective catalysts of hydrocyanation and hydroformylation.

13 cl, 30 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds that are represented by the following structural formulas:

The intermediate compound of formula (I), wherein the radicals R1 independently represent methyl, ethyl or n-propyl, for preparing a compound of formula (A), wherein X represents a group of formula (A-I) or (A-II), Y represents C11-C17alkyl, and Z is a direct bond, - (CH2)8- or -CH2-S-CH2-.

EFFECT: compound of formula (A) may be used for stabilizing organic material against thermal, oxidative or light-decomposition.

13 cl, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: method for preparing amides is carried out by reductive amidation of carbonyl compounds at elevated pressures and heated in the presence of a metal catalyst in a polar solvent, using as the reducing carbon monoxide. Instead of catalyst, salt or metal carbonyls are used. They are selected from the group consisting of rhodium, ruthenium, iridium, cobalt, iron. The molar ratio of amide carbonyl compound and the catalyst is (0.5-1.5):1.0:(0.005-0.05), it is preferably 1.5:1.0:0.01. As the solvent, tetrahydrofuran, acetonitrile, ethyl acetate, methylene chloride, alcohols are used. The process is carried out at a pressure of 5-150 atm and at a temperature of 30-250C.

EFFECT: technological and economical method for producing amides by reductive amidation of carbonyl compounds is suitable for use in industry.

6 cl, 30 ex

Up!