JP2604826B2 - Highly selective oxidation of primary alcohols to aldehydes - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a method for highly selective oxidation of primary alcohols, which can obtain aldehydes from primary alcohols in high yield.

[Prior art] Oxidation of primary alcohols to corresponding aldehydes is an important and basic reaction technique in synthetic organic chemistry, and is particularly useful for pharmaceuticals, agricultural chemicals and other compounds and intermediates of industrial raw materials. Widely used in the synthesis of

Various methods have been developed to oxidize primary alcohols to produce aldehydes. For example, in the case of using a heavy metal oxide such as manganese dioxide, chromic acid, or lead tetraacetate as the oxidizing agent, a toxic oxidizing agent is stoichiometric. The need for stoichiometric or higher leaves problems in the treatment of the post-reaction waste.

Another method using a stoichiometric amount of an oxidizing agent is a method using a hydrogen peroxide-metal salt (Can. J. Chem., 43, 2924 (1.
965)), a method using DMSO (dimethylsulfoxide) (Chem. Ber., 100, 3861 (1967)), and a method using potassium iron (IV) (J. Am. Chem. Soc., 80, 2038 (1958)). ), A method using nickel peroxide (J. Org. Chem., 27, 1597 (196)
2)), method using ruthenium complex (Tetrahedron Let
ters, 22, 1605 (1981)), a method using hypochlorous acid (Te
trahedron Letters, 1641 (1976)), etc., but all of these methods generally have low yields and have problems in industrial implementation.

In addition to these methods, a method using platinum black as an air oxidation method using a noble metal as a catalyst (Tetrahedron, 9, 67)
(1960)) and methods using palladium salts (Tetrahedron,
9,67 (1960)), but all of these methods have low yields and require high-temperature and high-pressure conditions,
It is economically disadvantageous because expensive precious metals are used.

Also, a method of oxidizing to an aldehyde corresponding to a primary alcohol under relatively confidential conditions using a nitrosonium salt has been developed. As such an oxidation method, for example, a method of generating a nitrosonium salt from an N-oxyl compound using a halogen such as bromine or chlorine as an oxidizing agent (J. Am. Chem. Soc., 10
6,3877 (1984): J. Org. Chem., 50, 3930 (1965)), copper,
A method using a metal compound such as iron (J. Am. Chem. Soc., 10
6,3374 (1984): J. Mol. Cat., 32,357 (1985): 31, 217 (1
985)), oxidation method using peroxide (J. Org. Chem., 40, 1988).
(1975): 40, 1860 (1975): 42, 2077 (1977)). However, these methods have to be carried out in an anhydrous system or require a stoichiometric amount or more of an N-oxyl compound, which is industrially difficult to carry out. In addition, a method using sodium hypochlorite as an oxidizing agent for the purpose of improving these (J. Org. Chem.,
52, 2559 (1987)). According to such a method, a catalytic amount of an N-oxyl compound is used, and a method is devised to continuously generate a nitrosonium salt to be used in a circulating manner. However, even in this method, a large amount of sodium hypochlorite is required, and therefore, when the method is carried out on an industrial scale, the following points become problems. That is, since sodium hypochlorite is unstable at high concentration, it is generally available and can be handled at about 12% concentration, and the use of sodium hypochlorite in an equivalent amount or more increases the volume of the reaction solution. As a result, the production efficiency is reduced, the waste liquid is increased, and the like, which is economically disadvantageous.

There is also a method in which a N-oxyl compound is electrolytically oxidized by a direct method to form a nitrosonium salt, and this is used as an oxidizing agent to oxidize a primary alcohol to an aldehyde corresponding to the primary alcohol (J. Am .Chem.Soc., 105,4492
(1983)). This method does not require a chemical oxidizer,
The N-oxyl compound is twice as much as the alcohol, and the adjustment of the nitrosonium salt by electrolytic oxidation is performed in a separate reactor from the oxidation of the alcohol. This is a so-called Excel-method (Ex-Cell Method). Is disadvantageous for industrial implementation, such as requiring a structurally complicated separation cell.

[Problems to be Solved by the Invention] In view of the above-mentioned prior art, the present inventors have conducted intensive studies to find a method capable of industrially obtaining an aldehyde from a primary alcohol in a high yield. N-
The oxidation of the oxyl compound to the nitrosonium salt and the oxidation of the primary alcohol to the corresponding aldehyde by the nitrosonium salt are performed in a single electrolytic cell, and the nitrosonium salt is regenerated using the N-oxyl compound as a catalyst. It has been found for the first time that aldehydes can be obtained with high yield and high current efficiency when oxidation of alcohol and alcohol is carried out continuously, and the present invention has been completed.

[Means for Solving the Problems] That is, the present invention uses an aqueous solution of an alkali metal bromide selected from lithium bromide, sodium bromide, and potassium bromide as an electrolytic solution. The present invention relates to a method for highly selective oxidation of a primary alcohol to an aldehyde, which comprises electrolyzing a primary alcohol and an N-oxyl compound.

[Operation and Examples] In the method of the present invention for producing an aldehyde by oxidizing a primary alcohol using a nitrosonium salt, an alkali selected from lithium bromide, sodium bromide and potassium bromide is used as an electrolyte. Using an aqueous solution of metal bromide,
First, a primary alcohol and an N-oxyl compound are electrolyzed in an aqueous solution of the alkali metal bromide to form a nitrosonium salt. This compound immediately oxidizes the primary alcohol to an aldehyde and returns to the original N-oxyl compound, which is again converted to a nitrosonium salt by an electrolytic reaction. Therefore, the nitrosonium salt is recycled in the process of the present invention.

In the present invention, since the oxidation of alcohols by the catalyst and the regeneration by the electrolytic oxidation of the catalyst are continuously performed in the same electrolytic cell, a non-diaphragm type electrolytic cell having the simplest structure can be used.

In the present invention, as the electrolytic solution, for example, a two-phase solution composed of water and a hydrophobic solvent, a hydrated homogeneous solution, a mixed solution composed of the hydrated homogeneous solution and a hydrophilic solvent, and the like are used.
An alkali metal bromide selected from lithium bromide, sodium bromide and potassium bromide is dissolved in the aqueous layer in advance.

An active bromine compound is obtained from bromine ions by inserting an electrode into the electrolytic solution to perform electrolysis, and this is caused to act on an N-oxyl compound contained in the same electrolytic cell to generate a nitrosonium salt. The resulting nitrosonium salt oxidizes the primary alcohol to an aldehyde and returns to the N-oxyl compound by itself, but the N-oxyl compound is again oxidized to an oxonium salt by the active bromine compound generated by the electrolytic reaction. And the N-oxyl compound is eventually recycled as an oxidizing agent from the primary alcohol to the aldehyde. The diagram is as follows.

(In the formula, X represents Br.) In practicing the present invention, a so-called continuous tank reactor apparatus is used in which a raw material is additionally supplied while a product is taken out of the reaction system in a batch mode as well as a continuous mode. Can also be used. In the present invention, a non-diaphragm type electrolytic cell simple in equipment can be used, so that a continuous reaction process is possible, which is an industrially advantageous method.

As the primary alcohol used in the method of the present invention, for example, a primary alcohol represented by the general formula: RCH ₂ OH (wherein R represents a hydrogen atom or an alkyl group having 1 to 50 carbon atoms)
It is a chain or cyclic compound having a graded hydroxyl group, and in the molecule of such alcohol, a functional group such as ketone, ester, amide, nitro, nitrile, halogen, sulfonyl, olefin, or phenyl, which is stable against oxidation of nitrosonium salt. May be included. Such a primary alcohol may have two or more primary hydroxyl groups in the molecule, and in this case, it is converted to a di (poly) aldehyde via a monoaldehyde. When a secondary hydroxyl group exists in the same molecule, it is converted to ketoaldehyde via hydroxyaldehyde. Specific examples of such primary alcohols include, for example, 1-propanol, 1-pentanol, 1-hexanol, 1-octanol, 1-decanol, 1-undecanol, cyclohexanemethanol, benzyl alcohol, β-phenethyl alcohol,
2-ethylhexanol, 1,8-octanediol, 1,1
0-decanediol, cyclohexanedimethanol, 1
-Methylsulfonyl-1-octanol, 2-nitro-
Examples include 1-decyl alcohol, 4-carboethoxy-1-butanol, heptadecafluoro-1-decanol and the like.

In the present invention, the N-oxyl compound used is represented by the general formula (I): (Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each represent an alkyl group having 1 to 30 carbon atoms, and R ¹ and R ⁴ may combine to form a cyclic compound. In this case, an unsaturated bond may be present in the ring, and a functional group such as an amino group, a carbonyl group, an amide group, a halogen, or a nitrile may be bonded to the carbon forming the ring. Which may have two or more N-oxyl groups in the molecule). Specific examples of such compounds include, for example, 2,2,4,
4-tetramethylazetidine-1-oxyl, 2,2-dimethyl-4,4-dipropylazetidine-1-oxyl, 2,
2,5,5-tetramethylpyrrolidine-1-oxyl, 2,2,
5,5-tetramethyl-3-oxopyrrolidine-1-oxyl, 2,2,5,5-tetramethylpyrrolidine-1-oxyl, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3- Carboxamide, 2,2,5,5-tetramethyl-3
-Pyrroline-1-oxyl-3-carboxylic acid, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-oxo-2,2,6,6-tetramethylpiperidine-
1-oxyl, 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-benzoyloxy-2,
2,6,6-tetramethylpiperidine-1-oxyl, 2,2,
6,6-tetramethylpiperidine-1-oxyl-4-carboxylic acid, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-cyano-2,2,6,6-tetra Methylpepyridine-1-oxyl, di-t-butylamine-n-oxyl, general formula: R ₇ OCO (CH ₂ ) ₈ CO ₂ R ₇ (where R ⁷ is ), The general formula: Wherein R ₇ is the same as described above.

The amount of these N-oxyl compounds used as catalysts is
The amount is 0.0001 to 10 mol, preferably 0.003 to 0.5 mol, per 1 mol of the primary alcohol. When the amount is less than 0.0001 mol, the yield decreases, and even if the amount is more than 10 mol, no further improvement in the effect can be expected, which is uneconomical.

The concentration of the halogen-containing compound in the aqueous alkali metal bromide solution ranges from 0.1% by weight to a saturated aqueous solution, preferably from 5% by weight to a saturated aqueous solution. At concentrations lower than 0.1% by weight, the reaction tends to be slow.

The pH of the aqueous solution is from 1 to 13, preferably from 4 to 12. pH1
If the pH is lower than 13, the reaction is slow. If the pH is higher than 13, the product becomes unstable and the yield decreases.

As a reaction solvent, the reaction can be carried out in an aqueous solution when the primary alcohol, which is the reactant, is water-soluble. Or a mixed solution of an aqueous solution containing an alkali metal bromide and a hydrophilic organic solvent. The organic solvent may be any organic solvent that is stable against oxidation of the nitrosonium salt. Specific examples of such an organic solvent include ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and 3-pentanone; acetonitrile, propione Nitriles such as nitriles and benzonitrile; halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride, dichloroethane, trichloroethane and chlorobenzene;
Aliphatic or alicyclic hydrocarbons such as pentane, hexane, cyclohexane, heptane, octane, cyclooctane; aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene; methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate , Methyl propionate, γ
Esters such as butyrolactone; ethers such as tetrahydrofuran, dimethoxyethane and dioxane; and other sulfolane. These organic solvents are used alone or as a mixed solvent of two or more kinds. When a heterogeneous solution consisting of water and a hydrophobic organic solvent is used, it is preferable to carry out the reaction smoothly by performing sufficient stirring.

As the electrode, an electrode used for a normal electrolytic reaction can be used, but the present invention is not particularly limited by the kind of the electrode. Specific examples of such an electrode include, for example, platinum, platinum black, carbon, titanium, stainless steel, nickel, lead oxide, and the like, and an electrode that has undergone processing such as surface treatment. Materials or different materials may be used.

As the electrolytic cell, for example, any of an electrolytic cell in which the positive and negative electrode chambers are separated by a diaphragm and a non-diaphragm type electrolytic cell can be used, but a non-diaphragm type electrolytic cell is usually used.

The current density is in the range of 0.001 to 10 A / cm ² while inserting the electrode into an electrolytic cell containing a primary alcohol, an aqueous solution containing a catalyst N-oxyl compound and an alkali metal bromide and a solvent, and stirring, preferably. 0.001 to 0.2 A / cm ²
It is adjusted to be within the range. Current density is 0.001 A / cm ²
When it is lower, the reaction requires a long time, and when it is higher than 10 A / cm ² , a high voltage is required, and the side reaction tends to increase.

In the present invention, the amount of electricity required for the reaction is theoretically 2 Faraday with respect to 1 equivalent of the hydroxyl group, but in order to complete the reaction, it is 2 to 10 Faraday, preferably about 2 to 6 Faraday. desirable.

The reaction temperature is in the range of −20 to 100 ° C., preferably −10 to 50
It is in the range of ° C. When the reaction temperature is lower than −20 ° C., the reaction rate is reduced, and when the reaction temperature is higher than 100 ° C., a side reaction occurs and the yield tends to decrease.

The reaction time varies depending on the size of the electrode used, the current density, the reaction temperature, the type and concentration of the primary alcohol, and other conditions, but is substantially determined by the amount of electricity per mole of the primary alcohol.

After the completion of the reaction, the hydrophobic solvent is separated, and the solvent is distilled off to obtain a crude product. If necessary, the corresponding aldehyde compound can be obtained by carrying out conventional post-treatments such as distillation, recrystallization and chromatographic purification.

Next, the present invention will be described in more detail based on examples, but the present invention is not limited to only these examples.

Example 1 172.3 mg of 1-undecanol in a 20 ml glass reaction vessel
(1 mmol), 2.8 mg (0.01 mmol) of 4-benzoyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 3 ml of methylene chloride and 5 ml of a 25% aqueous sodium bromide solution saturated with sodium bicarbonate. Then, two platinum electrodes (each having a surface area of 1.5 cm ² ) were inserted into this mixed solution, and a constant current electrolysis was performed at room temperature with stirring at a current value of 30 mA. The reaction was stopped by supplying 2.2-Faraday / mol of electricity, the methylene chloride layer and the aqueous layer of the reaction mixture were separated, and the aqueous layer was extracted with methylene chloride. The methylene chloride extracts were combined and concentrated, and the residue was purified on a silica gel column with n-hexane-hexane.
Purification by elution with a mixed solvent of ethyl acetate (7: 1), n-
160.1 mg of undecanal was obtained. In addition, an absorption peak was observed at 1725 cm ⁻¹ in the IR spectrum, and the presence of C = 0 was confirmed. The yield was 94% and the current efficiency was 91%.

The measurement results of the NMR spectrum of n-undecanal obtained below are shown.

(NMR spectrum (60 MHz (CDCl ₃ ), unit: ppm (TMS)) δ 0.88 (s, 3H, -CH ₃ ) 0.95 to 1.75 (brd, 16H, -CH _2- ) 2.45 (m, 2H, -CH _2- ) 9.82 (t, 1H, -CHO) Examples 2 to 6 4-benzoyloxy-2,2,2 used in Example 1
Instead of 6,6-tetramethylpiperidine-1-oxyl, an N-oxyl compound shown in Table 1 was used, and n-undecanal was obtained in the same manner as in Example 1 except that the current was passed until the reaction was completed. Incidentally, 1725 cm ^{-1 according} to the IR spectrum
The presence of C = 0 was confirmed by an absorption peak. The amount of electricity and the yield up to the completion of the reaction are also shown in Table 1.

Examples 7 to 9 4-benzoyloxy-2,2,6,6- used in Example 1
The amount of tetramethylpiperidine-1-oxyl added to the second
N-Undecanal was obtained in the same manner as in Example 1 except that the amount of electricity was changed to 2.0 as shown in the table and an electric quantity of 2.0 Faraday / mol was applied. The yield of n-undecanal obtained was
It is shown in the table.

Examples 10 to 12 Instead of the 25% aqueous sodium bromide solution (pH 8 to 9) saturated with sodium bicarbonate used in Example 1, an aqueous solution saturated with sodium bicarbonate having a sodium bromide concentration shown in Table 3 was used. The procedure was performed in the same manner as in Example 1, except that a quantity of electricity of 2-Faraday / mol was applied to obtain n-undecanaal.
The yield is shown in Table 3.

Examples 13 to 15 and Comparative Examples 1 and 2 Instead of the 25% aqueous sodium bromide solution saturated with sodium bicarbonate used in Example 1, an aqueous solution saturated with sodium bicarbonate having a halogen-containing compound concentration shown in Table 4 was used. use,
The amount of electricity shown in Table 4 was applied to obtain n-undecanal. The yield is also shown in Table 4.

Examples 16 to 17 The procedure of Example 1 was repeated, except that the electrodes shown in Table 5 were used instead of the platinum plate used in Example 1, to obtain n-undecanal. The obtained yield of n-undecanal is also shown in Table 5.

Examples 18 to 25 The same procedure as in Example 1 was carried out except that the organic solvent shown in Table 6 was used instead of the methylene chloride used in Example 1, and a current of 2 Faraday / mol was passed. -I got Undecanal. The yield of n-undecanal obtained was 6
It is shown in the table.

Examples 26 to 33 Instead of 1-undecanal used in Example 1, the seventh
Electrolysis was performed at an electric quantity of 2.0 to 6.0 Faraday / mol in the same manner as in Example 1 except that the alcohols shown in the table were used.
Table 7 shows the obtained products and yields.

Incidentally, NMR spectra of the product obtained in Examples 26~33 (60MHz (CDCl _3), unit: ppm (TMS)) and IR spectra are as follows.

(Example 26; 2-ethylhexanal) (A) NMR spectrum δ 0.80 to 1.03 (6H, —CH ₃ ) 1.20 to 1.80 (9H, —CH ₂ —, —CH <) 2.19 (t, 2H, —CH ₂₎ −) 10.02 (1H, —CHO) (B) IR spectrum 1730 cm ⁻¹ absorption (C = 0) (Example 27; n-heptanal) (A) NMR spectrum δ 0.90 (m, 3H, —CH ₃ ) 1.31 _{~1.63 (m, 8H, -CH 2} -) 2.39 (m, 2H, -CH 2 -) 9.79 (m, 1H, -CHO) (B) IR spectrum 1710 cm ^-1 absorption (C = 0) (example 28 n-dodecanal) (A) NMR spectrum δ 0.88 (m, 3H, -CH ₃ ) 1.28 to 1.62 (m, 18H, -CH _2- ) 2.42 (m, 2H, -CH _2- ) 9.78 (t, (1H, -CHO) (B) IR spectrum 1720 cm ^-1 absorption (C = 0) (Example 29; (A) NMR spectrum δ 0.85 to 2.09 (m, 10H, -CH _2- ) 2.25 (m, 1H, CH-) 9.7 (1H, -CHO) (B) IR spectrum 1720 cm ^-1 absorption (C = 0) (Example 30; 1,10-decanedialdehyde) (A) NMR spectrum δ 1.32 to 2.60 (m, 16H, -CH _2- ) 9.81 (t, 2H, -CHO) (B) IR spectrum 1720 cm ^-1 Absorption (C = 0) (Example 31; benzaldehyde) (A) NMR spectrum δ 7.40 to 8.0 (m, 5H) 10.05 (s, 1H, -CHO) (B) IR spectrum 1710 cm ¹ absorption (C = 0) ( example 32: 10-hydroxy undecanal) (A) NMR spectrum _{δ1.10 (s, 3H, -CH 3} ) 1.20~1.70 (m, 12H, -CH 2 -) 2.30~2.50 (m, 4H, -CH _{2 -) 3.75 (q, 2H} , -CH 2 -) 9.60 (t, 1H, -CHO) (B) IR spectrum 1720 cm ^-1 absorption (C = 0) (example 33; 10 ketone undecanal) (A ) NMR spectrum δ 0.88 (s, 3H, -CH _{3) 0.95~1.75 (brd, 16H,} -CH 2 -) 2.45 (m, 2H, -CH 2 -) 9.82 (t, 1H, -CHO) (B) IR spectrum 1725 cm ^-1 absorption (C = 0) Comparison Example 3 4-benzoyloxy-2,2,6,6- used in Example 1
The same operation as in Example 1 was carried out except that tetramethylpiperidine-1-oxyl was not added, and no n-undecanal was produced.

Comparative Example 4 4-Benzoyloxy-2,2,6,6- used in Example 1
4-instead of tetramethylpiperidine-1-oxyl
Benzoyloxy-2,2,6,6-tetramethylpiperidine
The same operation as in Example 1 was carried out except that 2.6 mg was used. As a result, n-undecanal was not produced at all.

Comparative Example 5 The same procedure was performed as in Example 1 except that a 5% aqueous solution of lithium perchlorate saturated with sodium bicarbonate was used instead of the 25% aqueous solution of sodium bromide saturated with sodium bicarbonate used in Example 1. At an electric charge of 2.0 Faraday / mol, n-undecanal was obtained in a yield of 11%.

Comparative Example 6 4-benzoyloxy-2,2,2 was placed in a 20 ml glass reaction vessel.
2.8 mg of 6,6-tetramethylpepyridine-1-oxyl (0.
01 mmol), 3 ml of methylene chloride and 25 saturated sodium bicarbonate
A 5% aqueous sodium bromide solution was weighed, and two platinum electrodes (each having a surface area of 1.5 cm ² ) were inserted into the mixed solution, and a constant current electrolysis was performed at room temperature with stirring at a room temperature of 30 mA.

The reaction was stopped by passing an electric quantity of 2.2 Faraday / mol. 172.3 mg (1 mmol) of 1-undecanol was added to the solution, and the mixture was stirred at room temperature.

After stirring for 1 hour, the methylene chloride layer and the aqueous layer of the reaction mixture were separated, and the aqueous layer was extracted with methylene chloride.
The methylene chloride extracts were combined and concentrated, and the obtained oil was purified on a silica gel column by elution with a mixed solvent of n-hexane-ethyl acetate (7: 1 by volume) to obtain n-hexane.
Undecanal 2 mg and unreacted 1-undecanal 155
mg. The obtained oil was identified by IR spectrum and NMR spectrum, and it was confirmed that the obtained oil was consistent with the data of n-undecanal obtained in Example 1. The yield was 1%.

According to the method of the present invention, oxidation of a nitrosonium salt of an N-oxyl compound and oxidation of the nitrosonium salt to an aldehyde corresponding to a primary alcohol can be performed in a single electrolytic cell. In addition, there is an effect that the aldehyde can be obtained with high yield and high current efficiency by continuously performing the regeneration of the nitrosonium salt and the oxidation of the alcohol.

Claims (1)

(57) [Claims] An aqueous solution of an alkali metal bromide selected from lithium bromide, sodium bromide and potassium bromide is used as an electrolytic solution, and a primary alcohol and an N-oxyl compound are electrolyzed in the aqueous solution of an alkali metal bromide. A method for highly selective oxidation of a primary alcohol to an aldehyde, characterized in that: