JPH0422893B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to the reaction of geranylamine derivatives or nerylamine derivatives in the presence of a hydrogen acceptor using a ruthenium-phosphine complex as a catalyst to produce citral enamine (3,7-dimethyl-1,3,6-
octatrienylylamine derivative) and a method for producing citral by hydrolyzing it. [Prior Art] Citral is important as a raw material for the synthesis of ionone, methylionone, vitamins A and E, as well as food fragrances, soap fragrances, and cologne fragrances. Citral has two stereoisomers, geranial (trans type) and neral (cis type), but for the purpose of perfumery, the mixture is treated as citral without distinguishing between these isomers. In this specification, the term citral is used to mean these isomers and mixtures. The source of citral was lemongrass oil, but recently it has been produced by air oxidation of geraniol from turpentine. That is, α-pinene is hydrogenated to form pinane, which is air oxidized to form hydroperoxide, then pinarol is formed, which is thermally decomposed to form linalool, isomerized to form geraniol and nerol, and this is dehydrogenated. You're getting citral. Also, JP-A-57-
According to No. 102831, amine oxide obtained by oxidation of N,N-diethylnerylamine is used as a raw material, and it is reacted with an acid anhydride, such as acetic anhydride or propionic anhydride, to increase the yield relative to the amine oxide. A method for obtaining citral at 51.4-53.7% is disclosed. [Problems to be Solved by the Invention] However, the above method has disadvantages such as a long number of steps and a low yield, and is not satisfactory. Therefore, it has been desired to develop a method by which citral can be obtained in good yield with simple operations. [Means for Solving the Problem] Under such circumstances, the present inventor was conducting research on the isomerization reaction of geranylamine derivatives and nerylamine derivatives, and found that the use of a ruthenium-phosphine complex as a catalyst would lead to an efficient reaction. The present invention was completed based on the discovery that citral enamine was obtained and that citral could be obtained in good yield with simple operations by hydrolyzing this. That is, the present invention provides the formula () or (), (In the formula, R ₁ and R ₂ represent lower alkyl groups,
or R ₁ and R ₂ are combined with adjacent nitrogen atoms to form a cyclic group or morpholino group having 4 to 5 carbon atoms) in the presence of a hydrogen acceptor. The present invention provides a method for producing citral, which comprises reacting with a ruthenium-phosphine complex as a catalyst to produce citral enamine, which is then hydrolyzed. To carry out the present invention, first, 0.005 to 0.02 mol of ruthenium-phosphine complex and 1 to 3 mol of hydrogen acceptor are added to 1 mol of raw material geranylamine derivative or nerylamine derivative, and 100 mol of hydrogen acceptor is added in the presence of a solvent. React at ~120°C for 10-20 hours. As a solvent, dimethylformamide, 1,3
Aprotic polar solvents such as -dimethyl-2-imidazolidinone, N-methylpyrrolidone, diethylene glycol dimethyl ether, tetrahydrofuran, and dimethyl sulfoxide can be used, and toluene and the like can be used as the aprotic nonpolar solvent. The amount of solvent used is preferably 1 to 5 times the amount (volume) of the raw material amine. After the reaction is completed, the solvent is recovered under reduced pressure. If a dilute solution of sulfuric acid, hydrochloric acid, acetic acid, etc. is added directly after the reaction without separating the citral enamine thus obtained from the reaction solution, it is easily hydrolyzed to produce citral. If this is purified by solvent extraction, distillation, etc., citral with a purity of 95% or more can be obtained. The geranylamine derivative or nerylamine derivative represented by the above formulas () and () used in the present invention is obtained by adding an amine compound and n-butyllithium to geranyl chloride or neryl chloride obtained by reacting geraniol or nerol with phosphorus pentachloride. It is easily produced by reacting the obtained amine lithium compound. Another method is telomerization using a secondary amine such as isoprene or myrcene using an alkali metal compound [K.
Takabe et al.: Tetrahedron Lett., 4009 (1972)]
[S. Watanabe et al.: Chem. Ibd., 231 (1973)]. The amine compounds used here include dimethylamine, diethylamine, di-n-propylamine,
Examples include di-isopropylamine, di-n-butylamine, pyrrolidine, piperidine, and morpholine. Hydrogen acceptors include holon, mesityl oxide, 1-octene, cyclohexene, limonene,
Cycloocta-1,5-diene, styrene, etc. are used, and among these, α,β-unsaturated ketones have high potency, and among them, mesityl oxide is preferred. The amount of hydrogen acceptor to be used is preferably approximately equivalent to that of the substrate; for example, if more than three times the amount is used,
There is a significant increase in by-products presumed to be Diels-Alder products. The ruthenium-phosphine complex used in the present invention is a complex in which a bidentate phosphine ligand is coordinated to ruthenium, and is represented by the following formula (). _Run X _o L _p A _q () (where,
(m represents 1 or 2, n represents 1 to 4, p represents 2 to 4, and q represents 0 or 1) Examples of such ruthenium-phosphine complexes include the following. Ru ₂ Cl ₄ (BINAP) ₂ Et ₃ N RuHCl (BINAP) ₂ RuH ₂ (BINAP) ₂ Ru ₂ Cl ₄ (T-BINAP) ₂ Et ₃ N RuHCl (T-BINAP) ₂ RuH ₂ (T-BINAP) ₂ Ru ₂ Cl ₄ (t-Bu-BINAP) ₂ Et ₃ N RuHCl (t-Bu-BINAP) ₂ RuH ₂ (t-Bu-BINAP) ₂ Ru ₂ Cl ₄ (1,4-Diphos) ₂ Et ₃ N RuHCl (1,4-Diphos) ₂ In the above compound, Et is an ethyl group, Ph is a phenyl group, BINAP is 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, T-BINAP is
is 2,2'-bis(di-paratolylphosphino)-
1,1'-binaphthyl, t-Bu-BINAP is 2,
2'-bis(di-paratertial-butylphenylphosphino)-1,1'-binaphthyl,
-DiPhos represents 1,4-bis(diphenylphosphinebutane. Such ruthenium-phosphine complexes are described, for example, in the literature [Y. Ishii et al.:
Tetrahedron Lett., 24 , 2677 (1983)] [Y.Ishii
et al.: Chem Lett., 1179 (1982)] [T. Ikariya et al.:
J.Chem.Soc.Chem.Commun., 922 (1985)]. For example, to give an example of making Ru ₂ Cl ₄ (BINAP) ₂ Et ₃ N,
First, ruthenium chloride and cycloocta-1,
5-Diene (abbreviated as COD) is reacted in ethanol solution to obtain [RuCl ₂ (COD)] _o [MA
Bennet et al.: Chemistry and Ibd., 1516,
(1959)]. Then, [RuCl ₂ (COD)] _o 1 mol
After 1.2 moles of BINAP and 4 moles of triethylamine are heated and reacted in a solvent such as toluene, the crystals are separated and purified by recrystallization in a solvent. Ruthenium-phosphine complexes can be used isolated as crystals or so-called “in situ”.
A ruthenium complex can be prepared and used directly in the reaction. In the present invention, when enamine is hydrolyzed to obtain citral, the aqueous layer separated is made alkaline with caustic soda etc., extracted with a solvent such as toluene, and then distilled to produce geranyl, an unreacted raw material. Amine derivatives or nerylamine derivatives or nerylamine derivatives can be easily recovered. Further, the amine of the geranylamine derivative or the nerylamine derivative, which is generated by decomposition during the reaction process, can be recovered with a recovery rate of 95% or more. [Example] Next, the present invention will be explained with reference to an example. Example 1 10.5 g (50 mmol) of geranyl diethylamine,
Ru ₂ Cl ₄ (BINAP) ₂ Et ₃ N0.423g (0.5 mmol),
26ml dimethylformamide, 6ml mesityl oxide
ml (60 mmol) was placed in a sealed tube and reacted at 120°C for 12 hours. After the reaction, a portion was taken out and trans-stilbene was added as an internal standard reagent.
GLC analysis was performed to determine the conversion rate and selectivity of the reaction from geranyl diethylamine to citral enamine. The conversion rate was 43.3% and the selection rate was 73.7%. Then, dimethylformamide was distilled off,
Add 50 ml of water and 50 ml of ethyl ether, cool to 0℃, slowly add 70 ml of 10% acetic acid dropwise, and add 50 ml of ethyl ether.
-5 and stirred for 2 hours. The mixture was separated into an aqueous layer and an oil layer, so the aqueous layer was extracted with ethyl ether, combined with the oil layer, washed with 5% hydrochloric acid and 10% aqueous sodium carbonate solution, and dried over magnesium sulfate. After distilling off the solvent, distill it to 80-85
2.34 g of citral (theoretical yield 71%) was obtained as a fraction of °C/1 mmHg. According to GLC analysis, this product was a 25:75 mixture of neral and geranial. In the above step, the aqueous layer separated by ether extraction after hydrolysis was cooled with ice water, made alkaline by adding 50% caustic soda aqueous solution, extracted with toluene, and distilled to obtain 1.51 g of diethylamine (recovered). (95% recovery rate) and 5.35 g (90% recovery rate) of unreacted geranyl diethylamine were recovered. Example 2 neryl diethylamine 10.5 g (50 mmol),
Ru ₂ Cl ₄ (BINAP) ₂ Et ₃ N0.423g (0.5 mmol),
26ml dimethylformamide, 17ml mesityl oxide
ml (150 mmol) was placed in a sealed tube and reacted at 100°C for 20 hours. After the reaction was completed, the same procedure as in Example 1 was carried out.
GLC analysis showed conversion rate of 36.0% and selectivity.
It was 58.1%. Then, dimethylformamide was distilled off, and 50 ml of water and 50 ml of ethyl ether were added.
The mixture was cooled to 0° C., and 70 ml of 10% acetic acid was slowly added dropwise thereto, the pH was adjusted to 4 to 5, and the mixture was stirred for 2 hours. The aqueous layer and the oil layer were separated, and the aqueous layer was extracted with ethyl ether, washed together with the oil layer with 5% hydrochloric acid and 10% aqueous sodium carbonate solution, and dried using magnesium sulfate. After distilling off the solvent, perform distillation at 80-85℃/1
mmHg fraction of citral 1.43 g (theoretical yield 52.3
%) was obtained. According to GLC analysis, this product was a 33:67 mixture of neral and geranial.
Also, in the same manner as in Example 1, 1.25 diethylamine
g (95% recovery) and neryl diethylamine 6.05
g (recovery rate 90%). Example 3 2.1 g (10 mmol) of geranyl diethylamine,
[RuCl ₂ (COD)] _o 28 mg (0.1 mmol), BINAP66
mg (10 mmol), dimethylformamide 5.2 ml,
1.2 ml (12 mmol) of mesityl oxide was placed in a sealed tube and reacted at 120°C for 12 hours. GLC analysis was performed in the same manner as in Example 1 to determine the conversion rate and selectivity of the reaction leading to citral enamine.
The conversion rate was 73.7% and the selection rate was 54.0%. Then, by treating in the same manner as in Example 1, the boiling point is 80~
0.59 g of citral at 85℃/1 mmHg (theoretical yield 52.5
%) was obtained. According to GLC analysis, this product was a 27:73 mixture of neral and geranial. Examples 4 to 12 Ru ₂ Cl ₄ used in Example 1
(BINAP) Citral was obtained from geranyl diethylamine in the same manner as in Example 1, using each ruthenium-phosphine complex instead of ₂ Et ₃ N. The results are shown in Table 1.

【table】

[Table] Examples 12 to 15 Citral was obtained in the same manner as in Example 1 except that each geranylamine derivative was used in place of the geranyl diethylamine used in Example 1. The results are shown in Table 2.

【table】

〔Effect of the invention〕

The present invention is a highly industrially valuable production method capable of producing useful citral using readily available geranylamine derivatives and nerylamine derivatives as raw materials in relatively short steps and in good yield.

Claims (1)

[Claims] 1 Formula () or () (In the formula, R ₁ and R ₂ represent lower alkyl groups,
or R ₁ and R ₂ are combined with adjacent nitrogen atoms to form a cyclic group or morpholino group having 4 to 5 carbon atoms) in the presence of a hydrogen acceptor. 1. A method for producing citral, which comprises reacting with a ruthenium-phosphine complex as a catalyst to produce citral enamine, which is then hydrolyzed.