JPS6220973B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the following formula () This relates to the production of safranal shown in Safranal is 0.4 in saffron (Iridaceae)
It is a component of essential oil containing ~1.3%, and is a type of terpene that has the unique aroma of saffron. Conventional methods for producing safranal include extracting it from the essential oil, or oxidizing β-cyclocitral obtained by hydrolyzing the bitter picrocrocin present in saffron. However, the yield in both methods is low, especially from β-picrocrocin, only 1-3%. The present invention relates to a production method characterized in that safranal can be obtained in high yield using geraniol derivatives () which naturally exist as free or ester forms as raw materials. The manufacturing method of the present invention will be diagrammed using chemical formulas, and each step will be explained in detail. (In the formula, R ₁ represents an acyl group, R ₂ represents an aryl group, and the numbers ~ represent each step.) The step is to add a geraniol derivative represented by the general formula () to the general formula () in the presence of a metal acetate and a solvent. ) R ₂ SeX ( ) (In the formula, R ₂ represents an aryl group) is a step of reacting an organic selenyl halide to lead to a compound represented by the general formula (). Examples of the metal acetate salts used include sodium salts and potassium salts, with sodium salts being preferred. As the solvent, lower fatty acids such as acetic acid and propionic acid are selected, with acetic acid being preferred. Examples of organic selenyl halides include phenylselenyl chloride and phenylselenyl cupromide. Regarding reaction temperature and reaction time, 0 to 100
℃ for up to 3 hours, preferably at room temperature for about 1 hour. The step is a step of ring-closing the compound () obtained in the step in the presence of an acid to obtain the compound (). Any solvent may be used as long as it does not participate in the reaction, but halogenated hydrocarbons such as methylene chloride, chloroform, and trichloroethane are preferably selected. The acid used may be either a mineral acid or an organic acid, but a strong organic acidic compound such as trifluoroacetic acid is particularly preferred.
It is sufficient that the reaction temperature is from cooling to room temperature and the reaction time is within 3 hours. The step is a step in which the closed ring product () obtained in the step is converted into selenium oxide (') using hydrogen peroxide. A solvent may or may not be used, but when it is used, methanol or the like is preferred. The reaction temperature is approximately from cooling to room temperature, preferably under ice cooling. A reaction time of 3 hours or less is sufficient. The step is to remove selenium by heating the selenium oxide compound (') obtained in the above manner in a suitable solvent, and to lead to the olefin compound represented by (). A suitable solvent may be any solvent as long as it does not participate in the reaction, but halogenated hydrocarbons such as carbon tetrachloride are preferred. Heating temperature is 0-100
℃, preferably around the boiling point of the solvent, and the reaction time is about 1 to 30 hours, preferably 10 to 20 hours. The process is the olefin body () obtained in this way.
This is a process in which the diolefin is dehydrated under a basic catalyst to obtain a diolefin (). For example, a method using thionyl halide in the presence of an organic tertiary amine such as pyridine is employed. As such thionyl halide, thionyl chloride and thionyl bromide are preferred. The solvent selected is one that does not directly participate in this reaction, such as methylene chloride, chloroform, trichloroethane, etc. The reaction temperature is from cooling to room temperature, and the reaction time is preferably within 3 hours, preferably within 1 hour under ice cooling. The step is a step of hydrolyzing the diolefin body ( ) obtained in the step to lead to an alcohol body ( ). As the hydrolysis method, commonly used known methods are employed. For example, hydrolysis is carried out using an alkaline agent in an alcoholic solvent such as methanol or ethanol, and examples of the alkaline agent include potassium hydroxide and sodium hydroxide. Although the reaction temperature and reaction time cannot be absolutely limited, it is preferable to carry out the reaction at 0 to 50°C for 1 to 24 hours, preferably at room temperature for 1 to 10 hours. This step is a step in which the alcohol () obtained as described above is subjected to an oxidation reaction in the presence of a base to lead to an aldehyde (). The oxidizing agent may be any known oxidizing agent that oxidizes alcohol to aldehyde, but chromium oxide is preferred. The base used in this step is selected from organic tertiary amines such as pyridine and triethylamine, with pyridine being particularly preferred. Although a solvent not directly related to this reaction is selected as the solvent, the above-mentioned organic tertiary amines can also be used as the solvent. A reaction temperature of 0 to 100°C and a reaction time of 24 hours or less are sufficient, preferably 0.5 to 3 hours at room temperature. The step is a step of heat-treating the aldehyde derivative () derived from the steps in the presence of a base to derive safranal represented by the general formula (). Such a basic substance is preferably an organic tertiary amine such as pyridine, substituted pyridine, or an alkylamine such as triethylamine, with pyridine being particularly preferred. In this step, heating may be performed in a basic substance alone, but this does not prevent the coexistence of a solvent, and such solvents are selected from those that do not directly participate in the reaction, such as benzene, toluene, and xylene. The reaction temperature is preferably 0 to 100°C, preferably around the boiling point of the solvent, and the reaction time is 1 to 24 hours, preferably 1 to 5 hours. In addition, as a purification method, a processing method known per se,
Examples include extraction, column chromatography, distillation, and recrystallization. In addition, the structures of the manufacturing intermediate products and safranal obtained in each process are referred to as infrared absorption spectra (hereinafter referred to as IR spectra), nuclear magnetic resonance spectra (hereinafter referred to as NMR spectra), and mass spectrometry spectra (hereinafter referred to as Mass spectra). Confirmation was made through elemental analysis, etc. EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited to these in any way. Example 1 Trans-7-acetoxy-1,1,5-trimethyl-2-phenylselenyl-octa-5-
En-1-ol [Formula: R ₁ = COCH ₃ , R ₂ =
Production of C ₆ H ₅ ] 200 mg of geranyl acetate (1.02 m mol) and 85 mg of sodium acetate (1.04 m mol) were added to 20 ml of acetic acid.
Dissolve in 20 ml of acetic acid under ice-cooling and stirring under a nitrogen stream.
phenylselenyl chloride (1.04 m
mol) 200mg dropwise. After stirring at room temperature for 15 minutes, 50 ml of water was added and extracted with benzene. After washing the benzene layer with saturated sodium bicarbonate solution,
Wash with saturated brine and dry with anhydrous sodium sulfate. The residue obtained by distilling off the solvent was subjected to alumina column chromatography to obtain 94 mg of a colorless oil from the benzene eluate. IR spectrum: (CHCl ₃ ) cm ^-1 3610 (OH),
1720 (C=O) NMR spectrum: δ (CDCl ₃ ) 1.26, 1.33,
1.67, 2.00 (3H, s, C H ₃ each) 3.70 (1H,
dd,

[Formula]) 7.18-7.70 (5H, m, ph Se) Mass spectrum: m/e 369 (M ⁺ ) Example 2 2-acetoxymethyl-3-hydroxy-1,
1,3-trimethyl-6-phenylselenylcyclohexane [Formula: R ₁ = COCH ₃ , R ₂ =
Production of C ₆ H ₅ ] Acetate obtained in Example 1 (0.51 m mol) 100
Dissolve mg in 5 ml of dry methylene chloride, and add 2.5 ml of trifluoroacetic acid under water cooling and stirring in a nitrogen stream.
Add and continue stirring for 15 minutes. After the reaction is complete, 20 ml of water is added, and the methylene chloride layer is washed with saturated aqueous sodium bicarbonate and saturated brine, and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was subjected to alumina column chromatography to obtain 65 mg of a colorless oil from the methylene chloride eluate. IR spectrum: (CHCl ₃ ) cm ^-1 3610 (OH),
1720 (C=O) NMR spectrum: δ (CDCl ₃ ) 0.90, 1.18,
1.30, 2.03 (3H, s, C H ₃ each) 3.01 (1H,
dd, 〓C H Seph) 4.7 (2H, m, -C H ₂ OAc)
7.2-7.7 (5H, m, ArSe) Mass spectrum: m/e 369 (M ⁺ ) Elemental analysis: C ₁₈ H ₂₆ O ₃ Se・0.2C ₆ H ₆ calculated value: C, 59.83; H, 7.12 Experimental value: C, 59.79; H, 7.35 Example 3 2-acetoxymethyl-3-hydroxy-1,
1,3-trimethyl-6-phenylselenoxycyclohexane [Formula': R ₁ = COCH ₃ , R ₂ =
C ₆ H ₆ ] Acetate obtained in Example 2 (2.36 m mol) 872
Dissolve mg in 2 ml of methanol and stir under ice cooling.
Add 5 drops of 30% hydrogen peroxide solution and continue stirring for 10 minutes. After the reaction is complete, add 10 ml of water and extract with benzene. The benzene layer is washed with saturated brine and then dried over anhydrous sodium sulfate. m. by recrystallizing the crystals obtained by distilling off the solvent from ethanol.
Obtain 420 mg of colorless needle crystals with p.139-140.5°. IR spectrum: (CHCl ₃ ) cm ^-1 3610 (OH),
1720(C=O) NMR spectrum: δ( _CDCl3 )4.60(5H,
broad s,

[Formula]) Mass spectrum: m/e 312 (M ⁺ -73) Elemental analysis: C ₁₈ H ₂₆ O ₄ Se Calculated value: C, 56.10; H, 6.80 Experimental value: C, 56.08; H, 6.89 Example 4 2-acetoxymethyl-3-hydroxy-1,
Production of 1,3-trimethyl-5-cyclohexene [formula: R ₁ = COCH ₃ ] The selenium oxide compound (1.06 m
Dissolve 410 mg (mol) in 50 ml of carbon tetrachloride and heat under reflux for 16 hours. The solvent was distilled off, and the resulting residue was subjected to silica gel column chromatography to obtain 210 mg of a colorless oil from the benzene eluate. IR spectrum: (CHCl ₃ ) cm ^-1 3610 (OH),
1720 (C=O) NMR spectrum: δ (CDCl ₃ ) 5.18-5.75 (2H, m, olefin proton) Mass spectrum: m/e 212 (M ⁺ ) Elemental analysis: C ₁₂ H ₂₀ O ₃ calculated value: C, 67.89; H, 9.50 Experimental value: C, 67.69; H, 9.22 Example 5 2-acetoxymethyl-1,1,3-trimethyl-3,5-cyclohexadiene [formula: R ₁
= COCH ₃ ] Acetate obtained in Example 4 (0.94 m mol) 200
Dissolve mg in 20 ml of methylene chloride, and add thionyl chloride (0.97 m mol) in a nitrogen stream while stirring on ice.
Add 115 mg and 90 mg of pyridine (1.2 mmol) and continue stirring for 5 minutes. After the reaction is complete, add 50 ml of water, wash with saturated potassium hydrogen sulfate, saturated sodium hydrogen carbonate, and saturated saline, and dry over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was subjected to silica gel column chromatography to obtain 162 mg of a colorless oil from the benzene eluate. IR spectrum: (CHCl ₃ ) cm ^-1 1720 (C=O) NMR spectrum: δ (CDCl ₃ ) 5.15-5.88 (3H, m, olefin proton) Mass spectrum: m/e 151 (M ⁺ -43) Elemental analysis :C ₁₂ H ₁₈ O ₂・0.5CH ₂ Cl ₂ Calculated value: C, 62.58; H, 8.09 Experimental value: C, 62.94; H, 8.05 Example 6 2-Hydroxymethyl-1,1,3-trimethyl-3 , 5-cyclohexadiene [formula] Acetate obtained in Example 5 (0.77m mol) 150
Dissolve mg in 10 ml of methanol, add 3 ml of 1N potassium hydroxide-methanol solution, and stir at room temperature for 4 hours. After the reaction is complete, add 50 ml of water and extract with benzene. The benzene layer was washed with saturated saline and dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent was subjected to silica gel column chromatography, and a colorless oil was obtained from the methylene chloride eluate.
Get 106mg. IR spectrum: ( _CHCl3 ) cm ^-1 3600 (OH) NMR spectrum: δ ( _CDCl3 ) 3.58-3.95
(2H, m, -C H ₂ OH) Mass spectrum: m/e 121 (M ⁺ -31) Elemental analysis: C ₁₀ H ₁₆ O・0.2CHCl ₃ Calculated value: C, 69.56; H, 9.27 Experimental value: C , 69.14; H, 8.79 Example 7 2,2,6-trimethylcyclohexer-3,5
Production of -diene-carboxaldehyde [formula] 3.3 g of pyridine and 330 chromium oxide (3.3 m mol)
After stirring for 1 hour, 2 ml of a pyridine solution containing 85 mg of the alcohol (0.56 mmol) obtained in Example 6 was added and the mixture was stirred for 1 hour at room temperature in a nitrogen stream. After the reaction is complete, add 50ml of water and extract with benzene. The benzene layer was washed with saturated aqueous potassium hydrogen sulfate, saturated aqueous sodium hydrogen carbonate, and saturated saline, and then dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent was subjected to silica gel column chromatography, and benzene-
23 mg of colorless oil was obtained from the hexane (1:1) eluate. IR spectrum: (CHCl ₃ ) cm ^-1 1710 (C=O) NMR spectrum: δ (CDCl ₃ ) 2.38 (1H, d,
〓C H -CHO) 5.4-6.1 (3H, m, olefin proton) 9.42 (1H, d, C H O) Mass spectrum: m/e 121 (M ⁺ -29) Example 8 Production of safranal [formula] Implementation Aldehyde obtained in Example 7 (0.15m mol) 23
mg was dissolved in 2 ml of pyridine and heated under reflux for 2.5 hours in a nitrogen stream. After the reaction is complete, add 10 ml of water and extract with benzene. The benzene layer was washed with saturated aqueous potassium hydrogen sulfate, saturated aqueous sodium hydrogen carbonate, and saturated saline, and then dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent was subjected to silica gel column chromatography, and benzene-
9 mg of safranal, a colorless oil, was obtained from the hexane (1:1) eluate. IR spectrum: (CHCl ₃ ) cm ^-1 1665 (C=O) NMR spectrum: δ (CDCl ₃ ) 1.21 (6H,
s, CH ₃ ×2) 2.17 (3H, s, CH ₃ ) 2.83 (2H,
s,

[Formula]) 5.37-5.70 (2H, m, olefin proton) 10.20 (1H, s, C H O) Mass spectrum: m/e 121 (M ⁺ -29)

Claims (1)

[Claims] Linear formula () When producing safranal represented by the general formula () (In the formula, R ₁ represents an acyl group) to a geraniol derivative represented by the general formula () R ₂ SeX () (In the formula, R ₂ represents an aryl group and X represents a halogen atom) Organic selenyl halide React with the general formula () (wherein R ₁ and R ₂ are the same as defined above) is obtained, and then ring-closed in the presence of an acid to form a compound of the general formula () (In the formula, R ₁ and R ₂ are the same as defined above) After forming a ring-closed product represented by the formula (wherein R 1 and R 2 are the same as defined above), it is converted into selenium oxide with hydrogen peroxide, and then deselenized, and the general formula () (In the formula, R ₁ is the same as defined above) is obtained, and then dehydrated under a basic catalyst to obtain the compound of the general formula () (In the formula, R ₁ is the same as the above definition) and then hydrolyzed to form the diolefin body represented by the formula () The alcohol shown by is obtained, and then an oxidation reaction is carried out in the presence of a base to obtain the formula () A method for producing safranal represented by the above general formula (), which comprises converting the safranal into an aldehyde represented by formula (2), followed by heat treatment in the presence of a basicity.