The method of producing iminodiacetonitrile
(57) Abstract:Use: in organic synthesis. Entity: an improved method of producing iminodiacetonitrile. Reagent 1: Hexamethylenetetramine or ammonia. Reagent 2: hydrogen Cyanide. Reaction conditions: Aqueous medium in the presence of an inorganic acid, the temperature range from 50°C to the boiling temperature, pH of the reaction mass was adjusted to 5.5 - 10 and the reaction mass is heated to 50 to 100°C for a time sufficient to convert by-products. Goal - increase the yield of the target product. 3 C.p. f-crystals. The invention is directed to a method of producing iminodiacetonitrile (IDAN), iminodiacetic acid (IDA) and their derivatives.It is well known that IDAN is a valuable intermediate compound to produce compounds, such as IDA. It is also well known that IDA is a valuable intermediate compound to produce other compounds. In fact, in the United States IDA produce in industrial quantities for use as intermediate compounds in the production of other compounds. There are many methods of obtaining as IDAN and IDA.For example, U.S. patent N 3886198 (Philbrook and others) discloses a method of obtaining th acid, hydrochloric acid and nitric acid, an aqueous mixture has a pH of 3-5, and the molar ratio of hexamethylenetetramine and hydrogen cyanide 1:(5-7). The water mixture is passed through a reaction zone of the tubular reactor at 50-120aboutC.U.S. patent N3988360 ( Gaudette and others) discloses a continuous method of obtaining IDAN continuous preparation of an aqueous reaction mixture containing hexamethylenetetramine, formaldehyde and hydrogen cyanide (molar ratio 1:(1-2,2):(6:9-8,6), through the continuous feed in a continuous reaction zone at 50-250aboutWith an aqueous solution of hexamethylenetetramine, having a temperature of 0-80aboutWith, an aqueous solution of formaldehyde having a temperature of 0-80aboutWith, and hydrogen cyanide, having a temperature of 0-25aboutC. the pH of the resulting aqueous reaction mixture is 5-10. The resulting IDAN you can select or you can hydrolyze with the formation of alkali metal salts of IDA, which you can select or, podkisst into IDA.U.S. patent N 4307037 (Suchsland and others) discloses a production method IDAN reaction of hexamethylenetetramine with hydrogen cyanide in acidic aqueous media. In this way the pH during the reaction from the beginning is 5.5 and 7.5, and then it is gradually reduced to 0.5-3.5 dobavit way to obtain IDAN reaction 1 mol, equivalent of hexamethylenetetramine with 2 mol. equivalents of formaldehyde and 8 mol. equivalents of hydrogen cyanide at 20-90aboutC and pH 5.5 to 6.5.Despite the fact that using the preceding methods, you can achieve satisfactory results, all of them suffer from one or more disadvantages. All previously used processes are formed of undesirable side reaction products, such as glycolytic, aminoacetonitrile, ammonium salts and the like.In this work provides an improvement of the previously used methods consists in the fact that most of the side products of the reaction in turn required IDAN, IDA and their derivatives and thereby increase the total outputs. Remove these by-products of the reaction is considerably simplified, since the amount of side reaction products is reduced.These and other advantages are achieved in a method of producing iminodiacetonitrile interaction in the reaction medium of ammonia with formaldehyde and hydrogen cyanide or hexamine from formaldehyde and hydrogen cyanide, in which the improvement is more subsequent stages of setting the pH of the reaction medium up to 5.5 to 10.0 and heating R is the reaction in the reaction medium in iminodiacetonitrile.As indicated previously, specialists in this field are numerous known methods of obtaining IDAN and IDA. Usually they represent the reaction between ammonia, formaldehyde and hydrogen cyanide at pH 3-7 and temperatures up to 120aboutC. on the other hand, the aqueous reaction mixture of hexamethylenetetramine, formaldehyde and hydrogen cyanide may react at temperatures up to 250aboutC. the Actual method used to obtain IDAN and IDA is not crucial in the improved method of this invention.However, we found that the method of the presented invention is particularly applicable to the production method IDAN or its salts, which can be hydrolyzed, and IDA interaction 2 mol. equivalents of formaldehyde with 1 mol. equivalent of hexamethylenetetramine and 8 mol. equivalents of hydrogen cyanide in the presence of a strong mineral acid, such as hydrochloric, sulphuric, nitric acid and the like, obtaining 4 mol. equivalents IDAN.This reaction usually proceeds at moderate temperatures, for example 20 to 60aboutC, and pH 5-6. This method reduces the number of undesirable side reaction products such as glycolytic, aminoacetonitrile and ammonium salts. Preferred much the AI ammonium salt.Regardless of the method by which get IDAN and IDA of hexamethylenetetramine or its precursors, ammonia and formaldehyde, the reaction of hexamethylenetetramine with formaldehyde and hydrogen cyanide, improvement, according to the presented method, makes unwanted side reaction products such as glycolytic, aminoacetonitrile and ammonium salts in the desired IDAN, salt IDA and their derivatives. In the method of the presented invention is not matter, periodic way or continuous IDAN received or its derivatives. The improved method includes an additional stage of setting the pH of the reaction medium up to 5.5 to 10.0, and heating the reaction medium to a high temperature for a time sufficient to convert by-products of the reaction environment in IDAN or its derivatives.Depending on the temperature and pH of the reaction medium IDAN pass through a number of derivatives to double salts IDA. Whereas opening presents, these derivatives can be obtained experienced by routine experiment.It was found that the presence of glucocontrol contributed to the evolution side reaction products in desire desired compounds in the absence of glucocontrol for to avoid the bad outputs require longer reaction times. In order to obtain high outputs of the desired compounds in a reasonable time, preferably with a molar excess of glucocontrol, compared with the number of aminoacetonitrile and ammonium salts.In the method according to the invention the pH of the reaction medium was adjusted to 5.5 to 10.0. At pH below 5.5 transformation of by-products of the reaction in the desired IDAN and its derivatives significantly slowed down, and at pH above 10.0 outputs become worse because of the formation of undesirable side reaction products, although formed a number IDAN and its derivatives. Preferably the pH of the reaction medium to bring to 6-8.You can use a number of ways to set the pH of the reaction medium. Suitable materials used for determining the pH include hydroxides of alkali metals such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like, or adding carbonates of alkali metals such as sodium carbonate, potassium carbonate and the like.To establish the pH of the reaction medium can also be used hydroxides and carbonates of alkaline-earth metals such as calcium hydroxide, the ammonium. Hydroxides of alkali metals are preferred. Especially preferred is sodium hydroxide because it is readily available and inexpensive.In the method of the invention, the temperature can be varied within wide limits. At temperatures above 100aboutWith proceeds adverse reaction, which gives a colored mass. Preferably, the reaction medium containing a molar excess of glucocontrol towards aminoacetonitrile and ammonium salts were heated to 50-80aboutC. At a temperature below the 50aboutWith the transformation of the by-products of the reaction in the desired IDAN or its derivatives is very slow. Especially, it is preferable to heat the reaction medium to a temperature of 60-80aboutC.At temperatures from 50 to 100aboutC and pH from 5.5 to 10.0 reaction is completed within about 5 hours At temperatures from 60 to 80aboutWith and preferably pH 6 to 8, the reaction according to the method of the invention is completed in less time, usually for 2 hoursAccording to the invention, it is desirable to remove from the reaction medium at least a certain amount, IDAN before setting the pH of the reaction medium and heating the reaction medium. IDAN can be isolated from the reaction medium range spooge, as at least some amount of IDAN was isolated from the reaction mixture, and the pH of the reaction mixture has set and the reaction mixture was heated for converting by-products of the reaction environment in IDAN or its derivatives, separated IDAN can be connected with the reaction medium and to hydrolyze the alkali metal hydroxide with the formation of double salts IDA. This double salt can be used as intermediate compounds or can be acidified to obtain the IDA. Hydrolysis IDAN takes place at a higher pH conditions known to specialists in this field. Education IDA from her double salts requires only the addition of an acid such as a strong mineral acid, under conditions known to specialists in this field.P R I m e R 1. This example illustrates one of the options presented to the invention, when IDAN not isolated from the reaction mixture prior to the conversion of by-products of the reaction in the desired connection.In a flask with a capacity of 150 ml with thermorelay equipped with a stirrer, thermometer and pH probe, add 34,15 g of hexamethylenetetramine, 6.25 g of 36% hydrochloric acid, 30,4 50% formalin, 34, 45 g of water and 53.8 hydrogen cyanide, pH of the reaction mixture is 5.5. The mixture is heated on the. the donkey additional heating for 2 hours at 75aboutWith the contents analyzed by high-performance liquid chromatography. The output of the composite IDAN is 96%.P R I m m e R 2. This example illustrates another option when IDAN separated from the reaction mixture before the reaction by-products make the desired connection.The procedure of example 1 is repeated, except that after the first stage heating for 2 h, the reaction medium is cooled to room temperature and the mixture filtered. It was determined that the output selected at this stage IDAN is 79%. The filtrate is transferred into a round bottom flask with a capacity of 250 ml, bring its pH to 7, and then heated to 75aboutC for 2 h the resulting mixture is combined with the original filtered IDAN and receive the composite output is 97%.For example, although the improved method according to the invention has been described as a batch process it is clear that it can be done in a continuous way. Thus, it is possible to carry out modifications without disconnecting from the essence of the described invention.The following examples 3 and 4 additionally confirm the claimed scope of the invention.P R I m e R 3. Repeat mediatory 50aboutWith over two hours, and bring the pH of the reaction medium up to 5.5. After additional heating for 5 h at 50aboutWith content analyzed by high-performance liquid chromatography. The output of the composite IDAN is 95%.P R I m e R 4. Repeat the methodology of the process accordingly to example 1 except that the mixture is heated from room temperature to 100aboutC for 2.5 h and the addition of 0.1 m sodium hydroxide pH adjusted to 10.After additional heating for 4 h at 100aboutWith the contents analyzed by high-performance liquid chromatography. The output of the composite IDAN is 94,5%. 1. The METHOD of producing IMINODIACETONITRILE interaction of hexamethylenetetramine or ammonia with formaldehyde and hydrogen cyanide in aqueous medium in the presence of an inorganic acid at an elevated temperature in the range from 50oC to the boiling point with getting the reaction mixture, characterized in that, to increase the yield of the target product, the pH of the reaction mixture obtained in the reaction was adjusted to 5.5 - 10 and the reaction mass is heated to 50 - 100oWith in a period of time sufficient to convert/SUP>C.3. The method according to p. 1, characterized in that the pH of the reaction mass is brought to 6 - 8.4. The method according to p. 1, characterized in that the pH is determined by adding alkali metal hydroxide, for example sodium hydroxide.
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a method for semi-hydrogenation of dinitriles of the general formula: NC-R-CN (I) wherein R means linear or branched alkylene or alkenylene group comprising from 1 to 12 carbon atoms to the corresponding aminonitriles. Method involves using hydrogen in the presence of catalyst based on nickel, cobalt, Raney nickel or Raney cobalt comprising, possibly, an activating element that is taken among the 6 group of the Periodic system of element by the IUPAC nomenclature in the presence of strong mineral base representing a derivative of alkaline or earth-alkaline metal or ammonium hydroxide. In carrying out the hydrogenation process the parent mixture comprises water in the weight concentration at least 0.5 weight% of the total content of liquid components of the above said mixture, diamine and/or aminonitrile that can be form from the hydrogenating dinitrile and non-converted dinitrile wherein the weight concentration of all three indicated components is from 80% to 99.5%. The semi-hydrogenation reaction is carried out in the presence of at least one the selectivity-enhancing agent that is taken among the group comprising the following components: - compound comprising at least one cyano-group not bound with carbon atom that is taken among the group comprising hydrogen cyanide, lithium, sodium, potassium, copper cyanide, chelate cyanides of K3[Fe(CN)6], K4[Fe(CN)4], K3[Co(CN)6], K2[Pt(CN)6], K4[Ru(CN)6], ammonium or alkaline metal cyanides, tetrabutyl ammonium cyanide, tetramethyl ammonium thiocyanide, tetrapropyl ammonium thiocyanide; - organic isonitrile that is taken among the group including tert.-octylisonitrile, tert.-butylisonitrile, n-butylisonitrile, isopropylisonitrile, benzylisonitrile, ethylisonitrile, methylisonitrile and amylisonitrile; - tetraalkyl ammonium or tetraalkylphosphonium hydroxide or fluoride is taken among the group comprising tetramethyl ammonium, tetraethyl ammonium, tetrapropyl ammonium, tetrabutyl ammonium, tetrabutylphosphonium; - the chelate coordination compound formed by at least one metal atom and at least carbonyl radicals that is taken among the group comprising organic compounds including carbonyl, phosphine, arsine or mercapto-groups bound with metal and taken among the group comprising iron, ruthenium, cobalt, osmium, rhenium, iridium and rhodium. Method provides enhancing the selectivity by the aminonitrile group.
EFFECT: improved preparing method.
13 cl, 2 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a method for semi-hydrogenation of dinitrile of the general formula: NC-R-CN wherein R means linear or branched alkylene group comprising from 1 to 12 carbon atoms to the corresponding aminonitrile in the liquid medium. Method is carried out in the presence of a catalyst, such as nickel or Raney nickel comprising an activating element taken among rhodium or iridium wherein the weight ratio (Rh or Ir)/Ni is from 0.05% to 10%. Method provides enhancing yield of aminonitrile.
EFFECT: improved and enhanced method.
21 cl, 3 ex
FIELD: organic chemistry, biochemistry.
SUBSTANCE: invention relates to compounds used as intermediates substances for inhibitors of transfer of cholesteryl ester protein (CETP) and methods for their preparing. Indicated compounds are represented by the following formulae:
wherein R is taken among methyl and benzyl and by the formula
wherein R represents methyl.
EFFECT: improved preparing method, valuable biochemical properties of inhibitors.
15 cl, 9 ex
FIELD: organic chemistry, chemical technology, catalysts.
SUBSTANCE: invention relates to a method for synthesis of aminonitrile from corresponding dinitrile. Method involves contacting dinitrile of the general formula R(CN)2 wherein R means alkylene group comprising from 2 to 25 carbon atoms with hydrogen-containing medium in the presence of a solvent, hydrogenation catalyst and an additive comprising tetralkyl ammonium cyanate for enhancing yield and/or selectivity by aminonitrile as the end product. Also, invention relates to the catalyst composition used in hydrogenation of dinitrile to aminonitrile comprising the combination (1) of the hydrogenation catalyst useful for hydrogenation of dinitrile of the general formula R(CN)2 wherein R means alkylene group comprising from 2 to 25 carbon atoms to aminonitrile, and (2) additive comprising compound of tetraalkyl ammonium cyanate.
EFFECT: improved method of synthesis.
15 cl, 10 ex
FIELD: organic chemistry.
SUBSTANCE: invention relates to chiral N-acetyl-alpha-amino acid salts and optically active beta-aminoalkylnitriles, in particular compound of formula IIa , wherein R is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl; Q is N-acetyl-alpha-amino acid. Also invention relates to method for conversion of racemic 3-amino-(C3-C7)-alkylnitrile of formula I to corresponding (R) isomer of formula IIf. Claimed method includes interaction of racemic 3-amino-(C3-C7)-alkylnitrile of formula I with N-acetyl-alpha-amino acid of formula Q in solvent. Also disclosed is method for conversion of R or S 3-amino-(C3-C7)-alkylnitrile to racemic 3-amino-(C3-C7)-alkylnitrile by interaction of R or S 3-amino-(C3-C7)-alkylnitrile with aqueous ammonia at 30-200°C. Composition useful as structure units in synthesis of optically active beta-amino acids, enriched with compound of formula IIa and compound of formula I, wherein Q is N-acetyl-alpha-amino acid; and R is as defined above also are disclosed.
EFFECT: new method for separation of 3-aminoalkylnitryles.
2 dwg, 8 ex
SUBSTANCE: method involves a step for hemihydrogenation in the presence of a strong base and a step for separating hexamethylene diamine and aminocapronitrile from the hemihydrogenation medium or hydrogenate. Hydrogenate is mixed with an acid and/or acid salt of an alkali metal or ammonia in an amount which is sufficient to maintain the relationship T defined by the formula T = [A] * na / [M] * nb, in which [A] is molar concentration of the anion of the corresponding acid or acid salt, [M] is molar concentration of the cation of the corresponding base or acid salt present, na is the charge value of anion A, nb is the charge value of cation M, T varies from 1.01 to 5. Further, said hydrogenate undergoes distillation to extract the head fraction of A mainly consisting of hexamethylene diamine, and a tail fraction of B consisting of aminocapronitrile, adiponitrile and high boiling point compounds.
EFFECT: method enables extraction of hexamethylene diamine from adiponitrile hemihydrogenation medium with high degree of purification, specifically very low content of tetrahydroazepine.
8 cl, 3 ex