PL93316B1 - - Google Patents

Description

The subject of the invention is a process for the production of 2,2,6,6-tetramethyl-4-ketopiperidine from acetone and ammonia. It is known to produce 2,2,6,6-tetramethyl-4-ketopiperidine, which consists in the fact that 2.2 The 4,4,4-pentylmethyl-2,3,4,5-tetrahydropyrimidine is reacted with a Lewis acid, preferably zinc chloride or calcium chloride, in the presence of water. The pyrimidine derivative used as a substrate can be produced from acetone and ammonia, but its isolation from the reaction medium and, if necessary, purification requires considerable work. Attempts have already been made to combine the two reaction steps, i.e. to carry out the preparation of 2,2,6,6-tetramethyl-4. ketopiperidine directly from acetone, without the isolation of pentamethyltetrahydropyrimidine - Appropriate tests did not show satisfactory yields, because the formation of reaction mixtures was cumbersome and associated with losses. From the German patent specification DOS No. 1695753.6 it is also known to obtain 2.2. , 6-Tetramethyl-4-ketopiperidine (triacetoneamine) by reacting a diacetone alcohol with ammonia in a ketone environment and in the presence of Lewis acid azMh.Chem. 99, page 1145, the Asinger process is known, which consists in reacting acetone with ammonia in the presence of CaCl2. The disadvantage of both methods is the necessity to use significant amounts of catalyst, reaching more than 50% of the acetone substrate, with a low yield of the order of 40-53 % of theoretical yield. It has surprisingly been found that by eliminating this drawback, the process yield is simultaneously considerably increased up to 82% of the theoretical yield of pure triacetoneamine, when the method according to the invention is followed. The process consists of two steps which can be carried out directly in succession, for example in one pot, so that it is primarily suitable for the multi-industrial production of tetramethylpiperidone. Process for the preparation of 2,2,6,6-tetramethyl-4-ketopiperidine from acetone and ammonia, according to the invention, a) acetone is reacted at a temperature of 5-60 ° C with ammonia in the presence of 0.2-12% of 2 93 316 molar acid catalyst based on the amount of acetone used, and b) reactions against with or without addition of further amounts of acetone, it is brought to completion by further heating, the total amount of acetone used in the reaction with respect to the amount of ammonia used in a molar ratio equal to or greater than 1 to 6: 1. In the first process step, preferably at least 0 15 moles of ammonia are reacted with acetone, but it is more expedient for practical reasons to saturate the reaction mixture with ammonia, therefore it is preferable excess ammonia The catalyst is either a Lewis acid such as aluminum chloride, tin tetrachloride or preferably boron trifluoride or an adduct of boron trifluoride, or a protic acid or a salt of a protic acid with ammonia or a nitrogen-containing organic base, especially a primary, secondary or a tertiary nitrogen base. Examples of such protic acids or acid components in the salts used as acid catalysts are, in particular, mineral acids, for example hydrochloric, hydrobromic, hydroiodic, nitric, sulfuric and phosphoric acids, sulfonic acids such as aliphatic or aromatic sulfonic acids for example methanesulfonic, benzenesulfonic, p-toluenesulfonic or naphthalenesulfonic acids, phosphonic or phosphinic acids, such as aliphatic or aromatic, for example methylphosphonic, benzylphosphonic, phenylphosphonic acid, dimethylphosphinic, diethylphosphinic, and phenylphosphinic acid, such as basic or tribasic aliphatic or aromatic carboxylic acids, for example saturated or unsaturated monobasic aliphatic carboxylic acids with 1-18 carbon atoms such as formic, acetic, chloroacetic, dichloroacetic, trichloroacetic, propionic, butyl, lauric, palmitic, acetic, methacrylic and cinnamic, saturated and unsaturated dibasic aliphatic carboxylic acids such as oxalic, malonic, succinic, adipic, sebacic, tartaric, apple, fumaric and maleic acids, tribasic aliphatic carboxylic acids such as citric acid, monobasic aromatic acids such as optionally substituted benzoic and naphthoic acids, and dibasic aromatic carboxylic acids such as phalic and terephthalic acid. Preference is given to monobasic and dibasic aliphatic or aromatic carboxylic acids and monobasic aromatic sulphonic acids such as acetic, succinic, maleic, benzoic, o-iodobenzoic acid, m-methylbenzoic, p-III-n-butylbenzoic, p-toluenesulfonic acid and cinnamic acid. . Suitable organic bases include aliphatic, alicyclic and aromatic, primary, secondary, and tertiary amines, saturated and unsaturated nitrogen bases. urea, thiourea and basic resin ion exchangers. These are primary aliphatic amines such as methylamine, ethylamine, n-butylamine, octylamine, dodecylamine, and hexamethylenediamine, secondary aliphatic amines such as dimethylamine, diethylamine, di-n-propylamine and diisobutylamine, tertiary amines such as thiethylamine, primary alicyclic amines. such as cyclohexylamine, primary aromatic amines such as aniline, toluidine, naphthylamine and benzidine, secondary aromatic amines such as N-methylaniline and diphenylamine, tertiary aromatic amines such as N, N-diethylaniline, saturated and unsaturated nitrogen bases example heterocyclic bases such as pyrrolidine, piperidine, N-methylpyrrolidone-2, pyrazolidine, piperazine, pyridine, picoline, indoline, quinuclidine, morpholine, N-methylmorpholine, 1,4-diazadicyclo [2.2.2] octane and triacetoneamine, urea, thiourea and strongly and weakly basic resin ion exchangers. Acetone and substances such as diacetoneamine and triacetoneamine are preferred. Preferred as salts include cyclohexylamine formate, pyridine formate, pyridine p-toluene sulfonate, di-n-butylamine acetate, di-n-butylamine benzoate, morpholine succinate, morpholine maleate, triethylamine acetate, male triethylamine succinate, triethylamine acetate, triethylamine acetate, triethylamine succinate, triethylamine maleate, aniline acetate, triacetoneamine p-toluenesulfonate and acetone hydrochloride. Particularly preferred are ammonium chloride or boron trifluoride or a mixture of both. These catalysts are introduced in an amount of 0.2-12 mol%, preferably 2-5 mol%, based on the amount of acetone used. As additional cocatalysts, potassium iodide, sodium iodide, lithium bromide, lithium iodide, lithium rhodium, ammonium rhodium, can be used. lithium cyanide, lithium nitrate, ammonium sulphide, bromine, iodine or bromide, iodide nitrate, methanesulphonate, benzenesulphonate or p-toluenesulphonate of ammonia, triethylamine, urea or thiourea, for example in an amount of 0.01-0.5 mol% based on the amount of acetone The reaction temperature is maintained at 5-60 ° C, preferably 5-35 ° C and particularly preferably 5-25 ° C in the first step. It has proved to be advantageous to add a mono- or multifunctional alcohol in the first step. Suitable alcohols for this purpose are, for example, methanol, butanol, cyclohexanol, alcohol, benzyl alcohol, ethylene glycol, diethylene glycol, propylene glycol, ethylene glycol monomethyl ether, or 2-ethylhexanol. Preference is given to using lower monohydric alcohols such as methanol, ethanol and isopropanol, with methanol being particularly preferred. The duration of this lower temperature reaction step is at least one, preferably three hours. One embodiment of the process according to the invention consists in adding a further amount of acetone and / or diacetone alcohol to the reaction medium at the end of the first step. or mesityl or furan oxide or diacetoneamine or triacetodiamine and the temperature is raised, preferably to 40-65 ° C. Usually, acetone is then added in an amount of at least 0.5, in particular 1, preferably 2 to 4 parts per part of the initially introduced amount of acetone. The above-mentioned acetone derivatives, preferably diacetone alcohol or a mixture thereof with acetone, can also be used as acetone. Moreover, it is preferable to add further amounts of catalyst to the reaction medium in the second step. This can take place with the addition of acetone or the derivative of acetone, or later .... The same substances as those introduced in the first stage of the procedure are suitable as catalysts, in particular boron trifluoride, ammonium chloride, concentrated sulfuric acid or hydrogen chloride. In the second stage of the procedure, b) it is preferable to carry out the reaction for 8-20 hours at 50-55 ° C, or at first for 2 to 7 hours at 50-55 ° C, and then within 2-6 hours at the boiling point under a reflux condenser, especially at a temperature of about 56-60 ° C. In both stages of the procedure, the reactions can be carried out under pressure, for example under a pressure of 1 to 30, especially 1 to 10, preferably 1 to 3 excess pressure atoms . In this case, it is possible to keep the temperature above 60 ° C. The isolation of tetramethylpiperidone can take place in a known manner, for example by adding water and separating as a hydrate, or by adding an acid such as hydrochloric, sulfuric or oxalic acid and separating as a salt either by adding an excess of liquor, in particular concentrated liquor, such as aqueous sodium or potassium liquor and separating as an organic layer, or by, in particular, by distillation after optionally neutralizing the catalyst with a base, such as sodium hydroxide, potassium hydroxide or sodium carbonate. The acetone used in the first step may to some extent contain water and / or acetone condensation products such as diacetone alcohol, mesityl oxide, phoron, diacetonoamine and / or triacetone diamine. Such an additive may have a beneficial effect on performance. A preferred condensation product of acetone is mesityl oxide, in particular diacetone alcohol. Due to this, it is possible to use as a raw material in the first stage of the procedure the distillate obtained during the distillation treatment carried out at the end of the second stage of the procedure, which consequently means a higher degree of acetone conversion. If the water content of the reaction medium increases too much during such a recycle, it is advisable to remove some of the water from the reaction mixture. This can be done in such a way that, at the end of the first step, a concentrated alkaline solution, for example soda ash, is added to the reaction mixture and, after brief stirring, the aqueous layer is separated. In the process according to the invention, it is also possible to use organic solvents for which, as particularly suitable include, for example, hydrocarbons such as aromatic hydrocarbons, for example benzene, toluene and xylene, aliphatic hydrocarbons, for example hexane, heptane and cyclohexane, further halogen hydrocarbons such as methylene chloride, trichlorethane, carbon tetrachloride, ethylene chloride, ethylene chloride and chlorobenzene, furthermore ethers such as tetrahydrofuran. dioxane and diethyl ether and nitriles such as acetonitrile, aprotic polar solvents such as sulfolane, acetonitrile, nitromethane, dimethylformamide, dimethylacetamide, tetramethylurea, hexamethylphosphoric amide and dimethylsulfoxide, and especially preferred unsubstituted alcohols such as or substituted aliphatic alcohols, especially lower alkanols, for example methanol, ethanol, propanol, isopropanol, and tert-butanol, and cyclohexanol, alcohol, benzyl, monomethyl, ethylene glycol ether, 1,3-propanediol glycol and most of all 1 - 4 carbon atoms, such as methanol, in addition to diacetone alcohol, forqn, diacetoneamine, triacetone diamine and mesityl oxide. Mixtures of the above solvents are also suitable. The following examples illustrate the method of the invention. The preferred embodiments of the method according to the invention are clearly shown in PL

Claims (2)

1. patent claims. Example 1 A suspension consisting of 11 g of ammonium chloride and a mixture of 340 g of acetone and 64 g of methanol is saturated in 12 hours at a temperature of 13-17 ° C with ammonia gas. The colorless oil obtained is then diluted with 350 g of acetone and, while stirring, the temperature is kept at 50 ° -55 ° C for 15-20 hours. The excess solvent is then removed by evaporation in a vacuum and 36 g of water are added to the reddish residue. The crystallization, starting at 0-5 ° C, is achieved by stirring for 2 hours until complete. 286 g of 2,2,6,6-tetramethyl-4-ketopyridine hydrate having a melting point of 55-60 ° C. are obtained in the form of slightly yellowish crystals. If the reaction mixture is neutralized with oxalic acid, the product is obtained in the form of an oxalic salt with a decomposition temperature of 180 ° C. An example. The procedure is analogous to that in example 1, except that in the second stage, together with the addition of acetone, 1.3 g of boron trifluoride dissolved in ether are introduced. The isolation of 2,2,6,6-tetramethyl-4-ketopiperidine is carried out analogously to example I. The procedure is analogous to that of Example 1 with the difference that instead of ammonium chloride 1.3 g of boron trifluoride dissolved in ether are used. In the second stage of the procedure, 11 g of ammonium chloride together with acetone are then added to the reaction mixture. Examples IV-VII. The suspension, consisting of ammonium chloride ligands, 340 g of acetone and 64 g of methanol, is saturated in 4 hours at 13-17 ° C with ammonia gas. The colorless oil obtained is then diluted with 900 g of acetone and kept at a temperature of 50-55 ° C for 15-20 hours with agitation. After the first 6 hours, 70 g of 97% sulfuric acid is added dropwise to the solution within 1-2 hours. At the end of the reaction time, the reaction mixture is adjusted to pH = - = 4.5-5 with 97% sulfuric acid within 1 * 2 hours. The resulting 2,2,6,6-tetramethyl-4-ketopiperidine bisulfate suspension is filtered at 5-10 ° C and washed with acetone. 655 g of the bisulfate salt are obtained, corresponding to 381 g of 2,2,6,6, -tetromethyl-4-ketopiperidine. If the procedure is analogous to that given above, but the amounts of acetone and sulfuric acid given below in Table 1 are used in the second stage of the procedure, the yields presented in the third column of this table are obtained. Table I 1 Example I V I VI I VII 1., \ Amount of acetone | in the second stage of the procedure 9Q0g 1140 g 670g Amount of sulfuric acid (added after 6 hours) 70g I 45g iii iii n »Yield 100% 1 2,2,6,6-tetramethyl-4-ketopiperidine 1 isolated] in the form of bisulfate) 1 342 g 1,402 g 1,349 J Example VII I. A suspension consisting of 11 g ammonium chloride, 340 g acetone and 64 g methanol is saturated in 4 hours at 13-17 ° C with ammonia gas. The colorless oil obtained is diluted with 900 g of acetone and is kept at 50-55 ° C under agitation for 15-20 hours. After the first 6 hours, the pH of the solution is adjusted to 8.5-8.6 by introducing about 23 g of gaseous hydrogen chloride. At the end of the reaction time and the reaction mixture is brought to a pH value within 1-2 hours with the aid of the hydrochloride. ** 5 ^ 6- The resulting suspension of 2,2,6,6-tetramethyl-4-ketopiperidine hydrochloride is filtered at a temperature 0-5 ° Cl washed with acetone. 400 g of the hydrochloride salt are obtained, corresponding to? 93 g of 2,2,6,6-tetramethyl-4-ketopiperidine. 2 of the mother liquor, after distilling off water and methanol and diluting the still residue with acetone, a further 95 g of the hydrochloride is isolated, corresponding to 70 g of 2,2,6,6-tetramethyl-4-ketopiperidine. Example IX. 40 g of gaseous ammonia are introduced into a mixture consisting of 126 g of acetone, 22.5 g of methanol and 4.7 ammonium chloride in about 4 hours at a temperature of 13-15 ° C. The reaction mixture is then stirred for a further 30 minutes at the same temperature, then 220 g of diacetone alcohol and 110 g of acetone are added, the whole is heated within 1 hour to 55 ° C and is kept at this temperature for another 12 hours. After and fractionated distillation, 125 g of 2,2,6,6-tetramethyl * 4-ketopiperidine are obtained. Example X. A suspension consisting of 11 g of ammonium chloride, 340 g of acetone and 64 g of methanol is saturated for 4 hours at 13-17 ° C with ammonia gas, then the colorless oil obtained is diluted with 900 g of acetone and kept at a temperature of 50-55 ° C for 15-20 hours with stirring. The resulting reaction mixture contains, according to the gas chromatogram, 378 g of 2,2,6,6-tetramethyl-4-ketopiperidine (triacetoneamine) which is isolated by distillation. Example XI. A suspension of 11 g of ammonium chloride, 340 g of acetone and 4 g of a 20% aqueous solution of ammonium sulfide is saturated for 4 hours at 13-17 ° C with ammonia gas. The next step is the same as in Example X. The reaction mixture finally contains 450 g of triacetoneamine. Example XII. Within 4 hours, a suspension of 11 g ammonium chloride, 340 g acetone and 1 g potassium iodide was saturated with gaseous ammonia. The following is the same as in Example X. The reaction mixture contains 400 g of triacetoneamine. If in this example potassium iodide is replaced with a suitable amount of one of the following cocatalysts: NH4Br, NH4N03, NH4J, LiBr, UJ, LiN03, NaJ, J2, urea nitrate, triethylammonium p-toluenesulfonate, NH4SCN or LiSCN, performance. Example XIII. The procedure is analogous to that in Example Xf, but instead of 64 g of methanol, 64 g of dioxane are used. The reaction mixture contains 314 g of triacetoneamine. Example XIV. The procedure is analogous to that of Example X, but instead of 64 g of methanol, 64 g of ethanol are used. The reaction mixture contains 363 g of triacetoneamine. Example XV. The procedure is analogous to that in Example X, but instead of 64 g of methanol, 64 g of isopropanol are used. The reaction mixture contains 350 g of triacetoneamine. Example XVI. The same result as in Example XV is obtained if 64 g of dimethylformamide are used instead of methanol. Example XVII. The procedure is analogous to that in example X, but no methanol is added. The reaction mixture contains 336 g of triacetoneamine. Example XVIII. The suspension, consisting of 11 g of ammonium chloride, 340 g of acetone and 64 of methanol, is saturated with gaseous ammonia for 4 hours at 13-17 ° C, then the colorless oil obtained is diluted with 1360 g of acetone and kept at a temperature of 50 ° C with stirring. 55 ° C for 15-20 hours. The resulting reaction mixture contains 420 g of triacetoneamine. Example XIX. The procedure is analogous to that in Example X, but after dilution, 900 g of acetone are first stirred at 50-55 ° C for 6 hours and then boiled under reflux (at 56-60 ° C) for 3 hours. The resulting reaction mixture contains 337 g of triacetoneamine. Example XX. The procedure is analogous to Example X, but instead of 11 g of ammonium chloride 5.5 g or 30 g of ammonium chloride are used, the results are given in Table 2 below. Table 2 i— Ammonium chloride and according to 5.5 38.0 I Amount of triacetoneamine 1 in the reaction mixture 1 220 1 381 I _1 Example XXI. The suspension, consisting of 20 g of ammonium bromide, 340 g of acetone and 64 g of methanol, is saturated in 4 hours at 13-17 ° C with gaseous ammonia, then the colorless oil obtained is diluted with 900 g of acetone and kept at a temperature of 50-40 with stirring. 55 ° C for 15-20 hours. The resulting reaction mixture contains, according to the gas chromatogram, 425 g of 2,2,6,6-tetramethyl-4-ketopiperidine, which is isolated by distillation. Example XXII. 18.7 g of liquid ammonia are introduced into a suspension consisting of 5.15 g of ammonium bromide and 420 g of acetone at a temperature of 24-26 ° C, and the reaction solution is kept under stirring for 7 hours at a temperature of 64-65 ° C. In this way, the triacetoneamine is obtained in high yield as in example XXI. Example XXIII. Proceeding analogously to example XXII but replacing the ammonium bromide with the appropriate amount of hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, dichloroacetic acid, propionic acid, oxalic acid, malonic acid, maleic acid , succinic acid, fumaric acid, benzoic acid, cinnamic acid or phthalic acid, the triacetonamine is obtained in a similarly high yield. Example XXIV. Proceeding analogously to example XXII but replacing the ammonium bromide with the appropriate amount of methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 6 93 316 BF3, ZnCl 2, NH4Cl, NH4J, NH4NO3, (NH4) 2SO4, ammonium formate, ammonium acetate, ammonium p-toluenesulfonate, p-toluenesulfonate, triethylammonium urea nitrate, urea p-toluenesulfonate, trihydrochloride pyrimine, pyridine formates with similarly high efficiency. Example XXV. The suspension, consisting of 16 g of ammonium nitrate, 340 g of acetone and 64 g of methanol, is saturated in 4 hours at 13-17 ° C with gaseous ammonia, then the colorless oil obtained is diluted with 900 g of acetone and kept at 50 ° C with stirring. 55 ° C within 15-20 hours. The resulting reaction mixture contains, according to the gas chromatogram, 380 g of triacetoneamine which is separated by distillation. Claimed Process for the preparation of 2,2,6,6-tetramethyl-4-ketopiperidine from acetone and ammonia, characterized in that acetone is reacted at a temperature of 5-60 ° C with ammonia in the presence of 0.2-12 mol% of catalysts based on the amount of acetone used and the reactions, in the event of the possible addition of further amounts of acetone, are terminated by further heating, the total amount of acetone used in the reaction to the amount of ammonia used in a molar ratio equal to or greater than 1.6 : 1. Wash. Typographer. UP PRL, circulation 120 + 18 Price PLN 45 PL