JPS6345662B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention is a raw material for producing quaternary ammonium salts that are widely used as hair rinses, fabric softeners, etc., and secondary amines that are useful as synthetic raw materials and intermediates for pharmaceuticals, agricultural chemicals, and fragrances. The present invention relates to a selective manufacturing method. More specifically, the present invention relates to a novel method for producing secondary amines by reducing oximes with specific reactants. [Prior art and problems to be solved by the invention] Secondary amines are used as raw materials for the production of various substances. For example, hexamethyleneimine is useful as a raw material for producing herbicides such as molinate herbicides, and various secondary amines are useful raw materials for the synthesis of geraniol and nerol, which are useful raw materials for perfumes and medicines, and as useful raw materials for perfumes. It is also useful as a raw material for the production of certain geranylamines. In addition, secondary amines are useful as raw materials for the production of various agricultural chemicals and pharmaceuticals. Furthermore, long-chain aliphatic secondary amines having two long-chain alkyl groups in the molecule can be used as hair rinses,
It is a useful material as a raw material for producing quaternary ammonium salts, which are widely used as fabric softeners. A method for selectively producing such useful secondary amines is to reductively alkylate a primary amine such as P-phenylenediamine with an aldehyde or ketone in the presence of hydrogen and a Pt or Pd catalyst to produce a secondary amine. How to manufacture. (Japanese Unexamined Patent Publication No. 123148/1983) is known, but this method requires an expensive catalyst and uses a primary amine as a starting material. Another known method is to nitrile fatty acids with ammonia and reduce them by adding hydrogen in the presence of a Ni catalyst to produce secondary amines (Japanese Unexamined Patent Publication No. 56-29546). However, it requires increased pressure and high temperature for reduction and uses a nitrile as a starting material. As a method for producing an amine from an oxime as a starting material, there is a method for producing an amine by reducing the oxime with hydrogen in the presence of a catalyst such as Ni (Japanese Patent Application Laid-open No. 116406/1983). As is known, this method produces primary amines as the main product. Also to oxime
Method for producing amines by reduction by acting with _LiAlH4 (J.Org.Chem.17, 294-297
(1952); hereinafter referred to as Document A) is also known, but primary amines are produced as the main products. That is, in Document A, when a specific oxime, for example acetophenone oxime, is used as an oxime, in addition to the main product, the primary amine α-phenylethylamine (yield 56%), the secondary amine N- Although it is described that ethylalinine (yield 16%) is also a secondary amine, it does not produce the secondary amine aimed at in the present invention with high selectivity.
That is, in the conventional methods for producing amines from oximes, particularly aliphatic oximes and alicyclic oximes, it has been difficult to produce the secondary amines aimed at in the present invention in high yield and with high selectivity. Furthermore, the present inventor proposed a method for producing an α-alkyl secondary amine by treating oxime sulfonate with trialkylaluminium to produce an imine, and further reducing it with diisobutylaluminum hydride as shown in the following formula ( J.Am.Chem.Soc.103,
7368−7370 (1981)). (In the formula, R′, R ¹ ′, R ² ′ and R ³ each represent a hydrocarbon group.) However, in this method, the target substance is obtained in two steps, and the oxime is mesylated or tosylated to convert it into a sulfonate. It is complicated because it has to be done. [Means for Solving the Problems] Therefore, in view of the above-mentioned situation, the present inventor conducted intensive research on a method for producing the desired secondary amine in a high yield and with high selectivity under mild conditions. We have arrived at the present invention. That is, the gist of the present invention is the following general formula [] (However, in the formula, R ¹ and R ² represent the same or different hydrogen or a hydrocarbon group having 1 to 30 carbon atoms, and the hydrocarbon group may contain a functional group that does not affect the reaction, and (R ¹ and R ² may combine to form a ring) The oxime represented by the following general formula [] R ³ R ⁴ AlH [] (However, in the formula, R ³ and R ⁴ are the same or different hydrogen or (representing a hydrocarbon group having 1 to 15 carbon atoms) is reduced with aluminum hydride to form the following general formula [] (However, R ¹ and R ² in the formula are the same as above.) A method for producing a secondary amine is provided, which is characterized by producing a secondary amine represented by the following. [Function] The oxime used in the present invention has the following general formula [] (However, in the formula, R ¹ and R ² are the same as above.) Preferably, it is a ketoxime. Specifically, acetoxime, benzophenone oxime, cyclohexanone oxime, propiophenone oxime, acetophenone oxime, α-tetralone oxime, 6-undecanone oxime, cyclododecanone oxime, dimethoxyacetophenone oxime, diphenylacetoxy Examples include dibenzylacetoxime, hexadecanophenone oxime, and 9-heptadecanone oxime. These oximes can be obtained by known methods, for example, by condensing the corresponding ketone and hydroxylamine hydrochloride under weak basic conditions. Aluminum hydride as a reactant used in the present invention is a compound represented by the following general formula [] R ³ R ⁴ AlH [] (wherein R ³ and R ⁴ are the same as above), and is preferably dialkyl aluminum. It is a hydride. Specifically, dimethylaluminum hydride, diethylaluminum hydride, methylethylaluminum hydride, diisopropylaluminum hydride, ethylisopropylaluminum hydride, diisobutylaluminum hydride, di-n-butylaluminum hydride, dihexylaluminum hydride, dioctylaluminum hydride, didecylaluminum hydride etc. can be exemplified. Particularly preferred is diisobutylaluminum hydride. Reduction is carried out in the presence or absence of a solvent. Examples of the solvent include solvents that do not affect the reaction between the oxime and the reactant, such as aliphatic hydrocarbons such as hexane and heptane, alicyclic hydrocarbons such as methylcyclohexane and cyclohexane,
Examples include aromatic hydrocarbons such as benzene, toluene, and xylene, halogenated hydrocarbons such as dichloromethane and monochlorobenzene, and ethers such as dioxane, tetrahydrofuran, dimethoxyethane, and diethylene glycol dimethyl ether. The molar ratio of reactant to oxime is usually 1 or more, preferably about 3 to 10. If there is too little reactant, the reduction will be incomplete; if there is too much, there will be no significant effect. Although the amount of inert solvent is not critical, it is usually about 1 to 20 inert solvent per mole of oxime. Reduction is usually carried out under an inert atmosphere such as nitrogen or argon. The order of addition of the oxime, dialkyl aluminum, hydride, and inert solvent is arbitrary. Reduction temperature is -50~150℃, preferably -10~30℃
It is ℃. If the reduction temperature is too low, the reaction rate will decrease. Moreover, if the temperature is too high, side reactions may occur. The reduction time varies depending on various other conditions, but
Usually it takes about 0.5 to 5 hours. The reaction product can be purified by well-known purification methods such as solvent extraction,
By appropriately using filtration, distillation, chromatography, etc., the desired secondary amine can be purified and isolated. [Examples] The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited to the Examples below. Example 1 Acetophenone oxime (135 mg, 1 mmol)
Diisobutylaluminum hydride (5 ml of 1M hexane solution, 5 mmol) was added dropwise to an anhydrous dichloromethane solution (10 ml) at 0°C under an argon atmosphere, and the mixture was reacted with stirring at 0°C for 2 hours. After the reduction reaction was completed, it was diluted with 20 ml of anhydrous dichloromethane and treated with sodium fluoride (840 mg, 20 mmol), followed by water (0.27 ml, 15 mmol). The suspension was stirred vigorously at 0° C. for 30 minutes, filtered, washed with dichloromethane and the solvent removed to give a colorless oil. The oily substance was purified by column chromatography packed with silica gel to obtain N-ethylalinine (111 mg,
A yield of 92% was obtained. Its NMR is as follows. δ6.23−7.15 (m, 5H, Ar−H), 3.06 (q, 2H,
J=7Hz, NCH ₂ ), 1.20(t, 3H, J=7Hz,
CH ₃ ), 1.20 (s, 1H, NH) Examples 2 to 4 Examples except that the compounds shown in Table 1 were used as oximes and the reduction reaction was carried out at the reaction temperature and reaction time shown in Table 1. The product secondary amine was prepared exactly as in Example 1. The results are shown in Table-1.

[Table] Also, its NMR is as follows. Example 2 δ2.29 (brt, 4H, NCH ₂ ), 1.28 (m, 14H,
CH ₂ ), 0.88 (brt, 6H, CH ₃ ) Example 3 δ7.02and7.07 (m, 10H, Ar-H), 3.65 (s,
2H, PhCH ₂ N), 2.73 (s, 4H, CH ₂ CH ₂ ), 1.10
(s, 1H, NH) Example 4 δ5.80-7.18 (m, 3H, Ar-H), 3.75 (s, 1H,
NH), 3.66and3.80(s, 6H, OCH ₃ ), 3.10(q,
2H, J=7Hz, NCH ₂ ), 1.18(t, 3H, J=
7Hz, CH ₃ ) Example 5

Diisobutylaluminum hydride (5 ml of 1M hexane solution, 5 mmol) was added dropwise to an anhydrous dichloromethane solution (10 ml) of the formula (1 mmol) at 0°C under an argon atmosphere, and the mixture was heated to 20°C with stirring.
Time reacted. After the reduction reaction, dilute with 20 ml of anhydrous dichloromethane and add sodium fluoride (840 mg,
20 mmol) followed by water (0.27 ml, 15 mmol).
mol). The suspension was stirred vigorously at 0° C. for 30 minutes, filtered, washed with dichloromethane and the solvent removed to give a colorless oil. The oily substance was purified by column chromatography packed with silica gel to obtain a secondary amine product.

[Formula] (111 mg, yield 92%) was obtained. Its NMR is as follows. δ6.30−7.03 (m, 4H, Ar-H), 3.40 (s, 1H,
NH), 2.57−3.07(m, 4H, NCH ₂ andAr−
CH ₂ ), 1.37−2.00 (m, 4H, CH ₂ CH ₂ ) Example 6 As an oxime

〔Effect of the invention〕

The production of secondary amines according to the present invention has great industrial value in that the desired product can be easily obtained under mild conditions with high selectivity and high yield.

Claims (1)

[Claims] 1. The following general formula [] (However, in the formula, R ¹ and R ² represent the same or different hydrogen or a hydrocarbon group having 1 to 30 carbon atoms, and the hydrocarbon group may contain a functional group that does not affect the reaction, and (R ¹ and R ² may combine to form a ring) The oxime represented by the following general formula [] R ³ R ⁴ AlH [] (wherein R ³ and R ⁴ are the same or different hydrogen or (representing a hydrocarbon group having 1 to 15 carbon atoms) is reduced with aluminum hydride represented by the following general formula [] (However, in the formula, R ¹ and R ² are the same as above.) A method for producing a secondary amine, which is characterized by producing a secondary amine represented by the following.