The isolation and purification of n-(hexyloxymethyl)caprolactam
(57) Abstract:The invention relates to a method of isolation and purification N-(hexyloxymethyl)caprolactam (CREPA), with insect - and aerorepublica activity. N-(hexyloxymethyl)caprolactam is produced by interaction of N-methylacetoacetate with excess hexanol in the presence of catalytic amount of concentrated hydrochloric acid. Isolation and purification of akrep is achieved in one stage by boiling the reaction mixture with aqueous alkali at atmospheric pressure with simultaneous distillation of hexanol in the form of an azeotrope with water. The invention relates to a method of isolation and purification N-(hexyloxymethyl)caprolactam with protecting and aerorepublica activity.N-(hexyloxymethyl)caprolactam is the technical name for akrep and is a highly effective repellent for protecting humans from the bites of blood-sucking insects and ticks.Akrep registered for cutaneous application. In this regard, there are restrictions on the content of impurities: the content of caprolactam and hexanol should not exceed 0.5% each (TU 2386-003. 00209266-94).According to the method of N-(hexyloxymethyl)caprolactam get vzaimodejstvie hydrochloric acid. Next, perform the isolation and purification of the obtained N-(hexyloxymethyl)caprolactam from unreacted caprolactam and excess hexanol. To this reaction mass is diluted with water, neutralized with sodium hydroxide solution and extracted with benzene. The benzene extract was separated and washed with water to dissolve the unreacted caprolactam. Then hold distillation of benzene at atmospheric pressure and the vacuum distillation of hexanol, after which the product is subjected to vacuum distillation.The disadvantage of this method of isolation and purification of akrep is a large amount of water leaching from equally good solubility of caprolactam in both water and in the organic phase. For more effective cleaning of caprolactam are forced to use benzene, which is highly toxic solvent and applies to flammable liquids. In addition, the vacuum distillation of a significant number of hexanol requires a powerful system to capture relatively low-boiling hexanol-1 to avoid losses. The need for regeneration of benzene and hexanol leads to considerable complication of the technological scheme.To address these shortcomings Fredericton, and hexanol.This is achieved by azeotropic distillation of hexanol with water directly from the reaction mass the stage of receiving akrep, excluding the extraction of the organic phase with benzene at atmospheric pressure in the presence of alkali. When using the separation vessel for collecting stratifying the azeotrope hexanol water it becomes possible to return the distillation of water in the reaction mass. When it was unexpectedly found that N-(hexyloxymethyl)caprolactam sustainable boiling with aqueous solutions of alkalis, whereas the caprolactam is hydrolyzed to 6-aminocaproic acid.Thus, if the reaction mass stage receiving akrep be boiled with aqueous sodium hydroxide solution, the water layer moves the hydrolysis product of caprolactam sodium salt of 6-aminocaproic acid, and hexanol Argonauts in the form of water azeotrope.The organic layer VAT residue represents the target product - akrep.The selection of CREPA, thus, is held in one technological stage, boiling of the reaction mixture with odnowionym solution. There is no need for high-vacuum distillation of the final product.Example. A mixture of 143 g (1 is the significance of 3 hours. Then the reaction mass is neutralized with 0.5 ml of 40% sodium hydroxide solution and washed with 700 ml of water. To the organic layer, add 700 ml of water and 100 ml of 40% aqueous caustic soda solution. The reaction mass is boiled away azeotropic mixture of hexanol with water. After separation of the azeotrope hexanol layer divert and water return in cubic Process is carried out until the content of hexanal and caprolactam <0.5% of each (according to GC).After the process is finished, the reaction mass is then cooled, the aqueous layer was separated. The organic layer was washed with 1 l of water (with the addition of NaCl) and vacuum drying at a temperature of 60-90oC.Obtain 205 g of the product containing 97% of the basic substance, 0.4% hexanol, 0.3% caprolactam and 0.5% moisture. The isolation and purification of N-(hexyloxymethyl)caprolactam obtained by the interaction of the N-methylacetoacetate with excess hexanol, from caprolactam and hexanol, wherein the process is carried out in one stage by boiling the reaction mixture with aqueous alkali at atmospheric pressure with simultaneous distillation of hexanol in the form of an azeotrope with water.
NH - OC6H13where R is H, CH3with insect - and aerorepublica activity
NH - OR1where R=C3H7when R1=C2H5-C4H9with insectrepellent activity
< / BR>where A denotes-CC-,, -CH=CH-(CIS), -CH2-CH2-,
X is hydrogen or halogen,
Y cyclohexyloxy group, or when X is hydrogen, Y is phenyl
or their salts with mineral or organic acids, with the property that specifically bind to Sigma receptors, in particular, with receptors of the Central nervous system that allows them to be used as protivoponosnye agents
R(I)where R is F, Cl, which have garmentindustry activity against microsomal cytochrome P-450-dependent monooxygenase system, liver, metabolizing foreign compounds - xenobiotics
where (a) X=-CH2-CH2-, R1=R2=CH3, R3=H, n=1;
b) X=-CH2-CH2-, R1=CH3, R2=CH2CH2OH, R3=H, n=1;
C) X=-CH2-CH2-, R1=C2H5, R2=R3=H, n=1;
g) X=-CH2-CH2-, R1=C2H5, R2=CH3, R3=H, n=0 or 1;
d) X=-CH2-CH2-, R1=R2=C2H5, R3=H, n=1;
e) X=-CH2-CH2-, R1=C2H5, R2=H-C3H7, R3=H, n=1;
W) X=-CH2-CH2-, R1=C2H5, R2=R3=CH3n=1;
C) X=-CH2-CH2-, R1=R2=R3=C2H5n=1;
and) X=-CH2-CH2-, R1=C2H5, R2and R3together = -(CH2)2O(CH2)2-, n=1;
K) X=-CH2-CH2-, R1=ISO-C3H7, R2=CH3, R3=H, n=0;
l) X=-CH2-CH2-5, R2=CH3, R3=H, n=0;
n) X=-CH=CH-, R1=R2=C2H5, R3=H, n=1,
that possess antiarrhythmic effect and can find application in medicine
Rwhere R1is hydroxy, lower alkanoyloxy, OCOT1Y2where: Y1, Y2is hydrogen, lower alkyl when X = CH2; R2group of the formula
ororor< / BR>ororwhere n' is 0,1,2,3; n = 2,1,0, where: Y3Y4is hydrogen, lower alkyl, Y5- phenyl-lower alkoxy, hydrogen, lower alkoxy when X is - S R2group
CHY5ororwhere Y3, Y5have the specified values;
R3lowest alkoxyl, lower alkyl, hydrogen, halogen, trifluoromethyl, lower alkylsulfonyl, R
FIELD: analytical methods.
SUBSTANCE: method of determining glycine when developing continuous protein fermentation processes consisting in preparing aqueous solution of glycine followed by extraction and further analysis of organic phase is characterized by that 20-35% by weight of lithium sulfate as salting-out agent is added to aqueous solution of glycine (pH˜5) and then solution is extracted with ternary mixture of hydrophilic solvents: 65-65.5% isopropyl alcohol, 20-20.5% acetone, and 14-15% ethyl acetate at volume ratio of extractant mixture to aqueous salt solution 1:10. Nonaqueous concentrate is further analyzed using potentiometric titration technique.
EFFECT: increased degree of glycine recovery to 98-99% and avoided use of dangerous reagents in organic phase analysis.
1 tbl, 11 ex
FIELD: organic chemistry, biochemistry, chemical technology.
SUBSTANCE: invention relates to a method for purification of synthetic 5-aminolevulinic (5-amino-4-oxopentaenic) acid hydrochloride (5-ALA) representing endogenous substance and biological precursor of porphyrines in living organism and plants. Preliminary purification of 5-ALA hydrochloride is carried out by electrodialysis of 5-ALA solutions with the concentration 140-300 g/l in current density 0.5-2.0 A/dm2 and at temperature 20-30°C. Proposed method of purification of 5-ALA hydrochloride provides isolating expensive preparation from filtrates and to enhance the content of basic substance in technical 5-ALA hydrolyzate prepared by catalytic and electrochemical methods with the parent content of basic substance 87.0%, not above, that results to enhancing yield of final 5-ALA hydrochloride. Purified substance can be used in research and industrial practice.
EFFECT: improved purifying method.
SUBSTANCE: anhydride is a physiologically active substance and can be used, for example, in chemotherapy as a low-toxic agent for inhibiting growth of carcinoma 755 (breast cancer). The object of the present invention is synthesis of a novel mixed anhydride based on dichloroacetic and aminoacetic acid which, for instance, enables to inhibit growth of carcinoma 755 (breast cancer) in monotherapy. The given task is solved through synthesis of a novel mixed anhydride based on dichloroacetic acid and aminoacetic acid of formula 1, which can be used in medical practice as an anti-tumour agent which enables, for example, to inhibit growth of carcinoma 755. The other objective of the invention is designing a method of producing the mixed anhydride based on dichloroacetic acid and aminoacetic acid. This task is solved using a method which involves successive reaction of aminoacetic acid with an alkali metal hydroxide in an aqueous medium followed by treatment of the reaction mass with dichloroacetyl chloride in a chloroalkane solution, acidation of the reaction medium with aqueous hydrochloric acid solution and extraction of the end product using existing techniques. The disclosed compound can be used in medical practice as an anti-tumour compound.
EFFECT: use of said compound in oncological practice inhibits growth of carcinoma.
2 cl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a method for preparing a solid form of the compound gadobenate dimeglumine of formula (I) used as a contrast agent for diagnostic visualisation, particularly in magnetic resonant tomography. The presented method involves spray drying of a liquid composition of the above compound. Preferentially, the liquid composition represents an aqueous solution. The invention also refers to a solid powder form of gadobenate dimeglumine prepared by the method described above, a pharmaceutical kit containing this form, and a method for preparing a solid form of 4-carboxy-5,8,11-tris(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecane-13 acid.
EFFECT: method enables preparing the high-yield and reproducible solid form of gadobenate dimeglumine, which possesses good flowability and dissolution rate.
15 cl, 3 ex
FIELD: amino acids, chemical technology.
SUBSTANCE: invention relates to methods for separation and isolation of individual aromatic amino acids from their mixtures. Proposed method is carried out by multiple-stage procedure by continuous passing the parent solution of mixture of phenylalanine and tyrosine through column packed with strong-base anion-exchange resin AV-17-2P in OH-form and in periodic change of temperature regimen. After saturation of sorbent with amino acids the process is carried out by turns at two temperature values by collecting two fractions in outlet. At value T1 = 20°C eluate is enriched with tyrosine as one component of the solution and at value T2 = 80°C - with another component, i. e. phenylalanine. By changing volumes of fractions colleted at different values of temperature the method provides, if necessary, to enhancing degree of purification of one component of the mixture. Process can be carried out both in mono- and multi-stage regimen and both different columns and a single the same column can be used as different stages. Proposed invention provides the separation method that results to the enhanced effectiveness for separation of mixture of phenylalanine and tyrosine and excluding accessory reagent from the technological process used in regeneration and conversion of ion-exchange resins to working form, elimination of flows and enhanced yield of amino acids. Invention can be used in chemical, microbiological, food processing industry and agriculture.
EFFECT: improved separating method.
4 cl, 6 tbl, 4 ex
FIELD: separation and cleaning of para-aminobenzoic acid.
SUBSTANCE: proposed method consists in increasing the concentration of salts of para-nitrobenzoic acid in reaction mass by obtaining the following ratio of sodium and ammonium salts: Na-salt : NH4-salt = 7.5-8.0 : 2.5-2.0 mole; acidation of solution of para-aminobenzoic acid is carried out with the aid of nitric acid at concentration of 20-25%. Novelty of invention consists in setting the required ratio of sodium and ammonium salts of para-nitrobenzoic acid and use of nitric acid for separation of para-aminobenzoic acid from solution.
EFFECT: increased productivity of equipment; high concentration of salts of para-nitrobenzoic acid; high purity of target product.
2 cl, 1 tbl, 4 ex
FIELD: preparative chemistry and technology.
SUBSTANCE: invention relates to a method for separating in fractionating a solution containing betaine and sucrose. Method involves chromatographic fractionation of this solution, nanofiltration and regeneration of fraction enriched with betaine and, possibly, fraction enriched with sucrose. Chromatographic separation is carried out in columns filled with material chosen from cation-exchange and anion-exchange resins, and nanofiltration is carried out with a membrane for nanofiltration chosen from polymeric and inorganic membranes having the limit value of passing through a column from 100 to 2500 g/mole. Solution for fractionation represents a solution prepared from sugar beet, for example, the black syrup solution.
EFFECT: improved method of betaine regeneration.
40 cl, 12 tbl, 3 dwg, 7 ex
FIELD: food industry, medicine.
SUBSTANCE: invention relates to a method for production of highly purified amino acid mixtures. Method involves separation of suspended particles and clearing protein hydrolyzate on clearing sorbent. Ammonia is removed from hydrolyzate by its passing through desalting system at the rate from 2 to 3 volumes per volume of desalting system/h followed by carrying out sorption of amino acids on cation-exchange resin in H+-form. Amino acids are eluted from cation-exchange resin with alkali solution and eluate is subjected for microfiltration and drying. Desalting system represents a system of succession connected ion-exchange column with alternating cation-exchange resin - anion-exchange resin wherein volume of anion-exchange resin provides exceed of its full ion-exchange capacity by 20-25% as compared with that in cation-exchange resin. Method provides enhancing effectiveness of ion-exchange purification of amino acids.
EFFECT: improved preparing method.
6 cl, 2 dwg, 1 tbl, 3 ex