RU2053225C1 - Method for production of n,n-di(cyclohexyl)amine of sorbic acid - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: N,N-di(cyclohexyl)amine is used as reagent 1, solution of sorbic acid chloride being used as reagent 2. Said reagent is prepared by interaction of equimolar quantities of sorbic acid and tonyl chloride in acid medium, organic solvent being used. Desired product is prepared in the medium of the same solvent being chosen of group which includes heptane, hexane and benzene. Molar ratio of sorbic acid and N, N-di(cyclohexyl)amine is 1:2.2, said amine being gradually added. Melting point of desired product is 75-79 C. EFFECT: improves efficiency of the method.

Description

 The invention relates to the chemistry of the production of sorbic acid amides (trans, trans-2,4-hexadiene acid), in particular to the production of N, N-di (cyclohexyl) sorbic acid amide of the formula (N State registration No. 506976).

CH ₃ CH = CHCH = CHCHN (cyclo-C ₆ H ₁₁ ) ₂ (I)
In the following, this amide is referred to as ditsamide. To date, a large number of sorbic acid amides have been synthesized (I, p. 53 et seq.); some of them are widely used in medical practice (like analeptics, local anesthetics, analgesics, germicidal preparations) and in agriculture (like fungicides, seed disinfectants, herbicides, insecticides, repellents) (I, p. 152-154). The production of sorbic acid amides is carried out in accordance with the technology widely used in organic chemistry, namely, by the interaction of sorbic acid chloride (hereinafter referred to as HASK) with the corresponding amine. So, for example, claimed [2] the use as herbicides and plant growth regulators of amides of 2,4-hexadiene acid of the formula
Ar-Y-CH (R) CH = CHCH = CHCHN (R ¹ ) ₂ , (II) where R = H atom or CH ₃ group; Y = O atom or divalent S atom; R ¹ = H atom, C ₁ -C ₄ alkyl, C ₂ -C ₄ alkenyl, C ₂ -C ₄ alkynyl, cyclo-C ₃ -C ₆ alkyl, phenyl, benzyl; Ar = (un) substituted phenyl, pyridyl, naphthyl, quinoline radical or phenoxy-phenyl or pyridyloxy-phenyl group.

Причем известен способ [2] получения эфиров формулы (III), тогда как в отношении получения кислот формулы (IV), хлорангидрида формулы (V), эфиров формулы (VI), тиолэфиров формулы (VII) и амидов формулы (II) используют классические методы, широко применяемые в органической химии, эфиры формулы (III) могут быть превращены путем гидролиза в карбоновые кислоты формулы (IV), из которых в свою очередь могут быть получены галогенонгидридов формулы (V), способные к реакции со спиртами, тиолами или аминами с образованием соответственно эфиров формулы (VI), тиолэфиров формулы (VII) или амидов формулы (II), в том числе и N,N-ди(циклогексил)амида 5-арилокси- или 5-арилтио-замещенной 2,4-гексадиеновой кислоты формулы (II), где R¹цикло-С₆-алкил (прототип).Amides of the formula (II), like ethers or thiol ethers, are obtained [2] from 2,4-hexadiene acid esters (mainly from methyl ether) of the formula (III)

Moreover, the known method [2] for the preparation of esters of formula (III), while in relation to the production of acids of formula (IV), acid chloride of formula (V), esters of formula (VI), thioethers of formula (VII) and amides of formula (II), classical methods are used widely used in organic chemistry, esters of formula (III) can be converted by hydrolysis to carboxylic acids of formula (IV), from which halides of formula (V) can in turn be prepared, capable of reacting with alcohols, thiols or amines to form respectively esters of the formula (VI), thioethers formula (VII) or amides of formula (II), including the N, N-di (cyclohexyl) amide of 5-aryloxy or 5-arylthio-substituted 2,4-hexadiene acid of the formula (II), where R ¹ cyclo- C ₆ -alkyl (prototype).

RCO-NR $\genfrac{}{}{0ex}{}{\text{1}}{\text{2}}$ +RCONHR $\genfrac{}{}{0ex}{}{\text{1}}{\text{2}}$ •HCl
В качестве акцептора НСl может использоваться другой амин, например пиридин и др. третичные амины. То есть этим методом процесс фактически от начала и до конца реакции осуществляется в щелочной среде. Любым этим методом может быть получен как хлорангидрид 2,4-гексадиеновой кислоты, например ХАСК, так и прототип и заявляемый дицамид. Недостатком этого метода является обособленность стадий получения и выделения хлорангидрида кислоты, например ХАСК и целевого амида, например дицамида; фракционирование ХАСК при высоком вакууме, что значительно затрудняет ведение процесса в производственных условиях, при этом остается значительное количество кубовых остатков, подлежащих сжиганию.The most common classical method for producing amides of 2,4-hexadiene acid and its substituted analogues is the interaction of an acid chloride, for example, HASA, with an amine (I, p. 53 et seq.). In turn, HASK can be obtained by a well-known method using various halogenating agents, for example, SOCl ₂ , POCl ₃ , PCl ₅ or others (I, p. 49 et seq.). In this case, the molar ratio of the reagents is acid: halogenating agent 1: 1 or more, HASK: amine = 1: 2 or more, the second amine molecule is an Hcl acceptor released during the reaction:
RCOCl + 2NHR $\genfrac{}{}{0ex}{}{\text{1}}{\text{2}}$ ___ → (RCO-NR $\genfrac{}{}{0ex}{}{\text{1}}{\text{2}}$ + HCl)

RCO-NR $\genfrac{}{}{0ex}{}{\text{1}}{\text{2}}$ + RCONHR $\genfrac{}{}{0ex}{}{\text{1}}{\text{2}}$ • HCl
As an acceptor of Hcl another amine can be used, for example pyridine and other tertiary amines. That is, by this method, the process is actually from the beginning to the end of the reaction in an alkaline environment. Any of this method can be obtained as acid chloride of 2,4-hexadiene acid, for example HASK, and the prototype and the inventive ditsamide. The disadvantage of this method is the isolation of the stages of preparation and isolation of an acid chloride, for example, HASA and the target amide, for example, dicamide; HACC fractionation at high vacuum, which greatly complicates the process in a production environment, while there remains a significant amount of bottoms to be burned.

In order to eliminate these drawbacks, reduce the energy intensity of the process and improve the state of aggregation of the target dicamide, a new modification of the method of producing dicamide is proposed, consisting in the fact that the solution obtained by the interaction of sorbic acid (SC) and thionyl chloride (molar ratio of reactants 1: 1) (pH 1-2) chloride, sorbic acid in an organic solvent (heptane, hexane, benzene) was added dropwise under stirring at 20-30 ^C. N, N-di (cyclohexyl) amine (DCHA), the molar ratio of the reactants SC: DCHA 1: 2.2. Then the reaction mixture was heated to boiling and allowed to extract for 5-6 h. The reaction mixture (pH 10.9) was cooled to 18-20 ° ^C. Thus the claimed method at the initial stage of the interaction of reactants in the process is an acidic environment (in the prototype alkaline environment), followed by neutralizing it and then alkalizing as the amine is added. The resulting hydrochloride of the starting amine is filtered off. The filter cake of the starting amine hydrochloride is washed with a solvent and sent for regeneration for reuse. The washing filtrate is attached to the main filtrate (dicamide solution in a solvent) and all together are successively washed with water (to remove water-soluble salts), 5% hydrochloric acid to pH 3-4 (to remove unreacted and excess starting amine), again water to pH 7. Then the solvent is distilled off under reduced pressure (100-300 mm RT. Art.) in a water bath. The distillation process is stopped after taking at least 2/3 of the initial amount of solvent, then the bottom residue is poured hot while stirring into a container (crystallizer) and gradually cooled with stirring and constant cooling. Strictly ensure that during crystallization there is no heating of the mixture.

-

C

-

C

-

-N

C 166,75 (С-1), 121,67 (С-2), 141,55 (С-3), 130,74 (С-4), 136,26 (С-5), 18,60 (С-6); кольцо: 56,62 (С-1 ), 31,35 (С-26 ), 26,5 (С-35 ), 25,58 С-4 ); молекулярная масса: найдено 275, вычислено 275,44.The yield of the target dicamide is 53-57%, based on the sorbic acid taken in the reaction; the content of the main substance is 98.3-99.8 (GLC). _Mp 75-79 ^{° C} (dec.). The structure of the obtained amide was proved by ¹³ C NMR and mass spectrometry:
C

-

C

-

C

-

-N

C 166.75 (C-1), 121.67 (C-2), 141.55 (C-3), 130.74 (C-4), 136.26 (C-5), 18.60 ( C-6); ring: 56.62 (C-1), 31.35 (C-26), 26.5 (C-35), 25.58 C-4); molecular weight: found 275, calculated 275.44.

 PRI me R 1. Obtaining N, N-di (cyclohexyl) amide of sorbic acid in heptane.

 Obtaining sorbic acid chloride (HASK).

In a three-necked flask equipped with a reflux condenser, dropping funnel, thermometer, stirrer, water cooling and heating, 33.6 g (0.3 g mol) of sorbic acid and 700 ml of heptane are charged. To the resulting suspension, 35.75 g (0.3 g mol) of thionyl chloride are added dropwise with constant stirring from a dropping funnel; the molar ratio of reagents is 1: 1. Temperature should not rise above 50 ^C. After loading the calculated amount of thionyl chloride the temperature of the flask was raised to reflux and allowed to extract at this temperature with stirring for 5-6 hours. After soaking, the reaction mass is cooled to ^about 18-28 C and filtered off from unreacted acid. The filtrate is a solution of sorbic acid chloride in a solvent (heptane) is sent to the next stage.

 Obtaining N, N-di (cyclohexyl) sorbic acid amide (dicamide).

The solution obtained above of a solution of sorbic acid chloride in heptane is loaded into a flask. Then, 119.66 g (0.66 g-mol) of N, N-di (cyclohexyl) amine (DCCA) are added dropwise with stirring. The molar ratio of HASK: DCCA is 1: 2.2. DCHA dripping spend slowly at a bottom temperature of not higher than 30 ^C. After the calculated amount load DCHA temperature in the reaction mass raised to reflux and holding at this given temperature and stirring for 6 hours. After this time the reaction mixture solution in ditsamida solvent and unreacted excess starting amine residues DCHA hydrochloride salts of sulfur compounds is cooled to 18-20 ^{° C} and the starting amine hydrochloride was filtered off DCHA. DCAH hydrochloride on the filter is washed 2-3 times with a solvent and sent for regeneration. The washing filtrate is attached to the main filtrate and then all together are successively washed with water and 5% hydrochloric acid to pH 3-4. Precipitated in the latter case, DCAH hydrochloride is filtered off and sent for regeneration. The filtrate is transferred to a separatory funnel and the layers are separated: the acidic aqueous layer is sent to neutralization, and the organic layer is washed with water until neutral and the solvent is distilled off under reduced pressure (100-300 mm Hg), making sure that the temperature in the reaction mass did not exceed 45-50 ° ^C. The distillation is stopped after the selection process is not less than 2/3 of the solvent of the charged initially to the reaction. Then, the bottom product is transferred to a crystallizer equipped with a thermometer and stirrer and slowly cooled to 5-7 ^{° C,} taking care to avoid reheating crystallising mass. The white crystallizing product which precipitated in this case is filtered off, washed on the filter with a chilled solvent and dried. Thus, 39.7-43 g of the desired amide are obtained, which is 48-52% of theory, based on the sorbic acid taken in the reaction. From the filtrate, after separation of the bulk of the crystals of dicamide under further condition in the cold, 4.2-5.1 g or 5.1-6.2% of the target product are additionally isolated. Thus, the total yield of the target ditsamide is 54.2-7.1%
The content of the main product is 98.7-99.8% (GLC). T _pl. = 75-79 ^{° C} (dec.).

 PRI me R 2. Obtaining N, N-di (cyclohexyl) amide of sorbic acid in hexane.

 The process design, the number of reaction components and solvent to be loaded, the preparation, isolation and purification of the target product are the same as in Example 1. The difference is that hexane is used as a solvent instead of heptane.

Obtain immediately 32.6 g (38.7%) of crystalline ditsamide, and then, upon further standing in the cold for 2 days, another 13 g (15.7%) was obtained. Thus, 45.6 g of ditsamide was obtained, which is 54.4% of theory, based on the sorbic acid taken in the reaction; the content of the main substance is 99.8% T _pl. = 76-78 ^{° C} (dec.).

 PRI me R 3. Obtaining N, N-di (cyclohexyl) amide of sorbic acid in benzene.

 The hardware design of the process, the number of reaction components and solvent loaded, the preparation, isolation and purification of the product are the same as in Example 1. The difference is that benzene is used as a solvent instead of heptane.

24 g (29%) of crystalline dicamide are obtained immediately and then, after further standing in the cold for 5-7 days, another 20 g (24.2%) is obtained. Thus, 44 g of the target ditsamide was obtained, which is 53.2% of theory, based on the sorbic acid taken in the reaction; the content of the main substance is 98.3-99.63% T _pl. = 75-79 ^{° C} (dec.).

Claims (1)

 METHOD FOR PRODUCING N, N-DI (CYCLOGEXYL) AMBIDE OF SORBIC ACID, characterized in that the N, N-di (cyclohexyl) amine is reacted with a solution of sorbic acid chloride, obtained by reacting equimolar amounts of sorbic acid and thionyl chloride in an organic medium , and the process is conducted in the medium of the same organic solvent selected from the group: heptane, hexane, benzene, with a molar ratio of sorbic acid chloride and N, N-di (cyclohexyl) amine 1: 2.2 with the gradual addition of amines on.