JPH02107791A - Oxidation of secondary alcohol to ketone - Google Patents

Abstract

PURPOSE:To produce ketone with high current efficiency in a high yield by electrolytically oxidizing sec. alcohol together with an N-oxyl compd. in an aq. soln. of a halogen-contg. compd. as an electrolytic soln. CONSTITUTION:Sec. alcohol such as 2-pentanol is electrolytically oxidized together with an N-oxyl compd. such as 2,2,4,4-tetramethylazetidine-1-oxyl in a two-phase ununiformly mixed soln. consisting of a hydrophobic org. solvent such as acetone and an aq. soln. of about pH 1-13 prepd. by dissolving a halogen-contg. compd. such as lithium chloride to about 0.1wt.% to saturation concn. At this time, the current density is regulated to about 0.001-10A/cm<2>, the quantity of electricity to about 2-10 Faraday per 1 equiv. hydroxyl group and the reaction temp. to about -20 to 100 deg.C. After the end of the reaction, the org. solvent is separated, the water is distilled off and the resulting crude product is purified as usual to obtain ketone corresponding to the sec. alcohol.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for oxidizing secondary alcohols to ketones, which allows ketones to be obtained from secondary alcohols in high yield.

[Prior art] Oxidation of secondary alcohols to convert them into corresponding ketones is an important reaction technique in organic synthetic chemistry, and is particularly used in the synthesis of compounds useful in pharmaceuticals and agricultural chemicals, as well as intermediates for industrial raw materials. It is widely used.

Various methods have been developed to produce ketones by oxidizing secondary alcohols. For example, methods using chromic acid, permanganic acid, their salts, or heavy metal compounds such as lead tetraacetate as oxidizing agents have been developed to produce ketones in a stoichiometric amount. Since this method requires a toxic oxidizing agent in a larger amount, problems remain in the treatment of waste after the reaction.

Another method using a stoichiometric amount of oxidizing agent is DM
There is an oxidation method using SO (dimethyl sulfoxide), but it is industrially problematic because it requires the reaction to be carried out at an extremely low temperature of -eo'c in an anhydrous solvent.

In addition to these methods, air oxidation methods and catalytic dehydrogenation methods that use precious metals as catalysts are known, but since the reactions are generally carried out at high temperatures, they have the drawback of easily causing side reactions, and are economically expensive. This is a great method.

Therefore, the development of a method to catalytically oxidize alcohol under mild conditions has attracted attention, and a method for oxidizing secondary alcohols that utilizes the strong oxidizing ability of ruthenium tetroxide has been developed (
L, M, Bcrkowltz; JAm, Chem, So
s, , 80.8682 (1958); R, M, M
orlarty;Tctrahcdron Lett,
, 4003 (1970); M, NJhcng U.S. Pat. No. 3,997.578: S, Torll; J.

Org, Cbei, 155 (1986): Tokko Akira [
Publication No. 13-42711. According to this oxidation method, an electrolytic reaction is used in the process of regenerating ruthenium tetroxide from ruthenium dioxide, but ruthenium dioxide is produced in a small amount, and slurry adheres to the electrodes, reducing production efficiency. There are drawbacks.

In addition, 2 under relatively mild conditions using nitrosonium salt
A method of oxidation to ketones corresponding to alcohols has been developed. To generate nitrosonium salts from N-oxyl compounds, oxidation with halogens such as bromine and chlorine (
J, Ats, Cham.

Soc, L06, 3877 (1984): J, Org.
, Chem, 50.3930 (1985)), copper,
Method of oxidizing with metal compounds such as iron (J, Am,
Chem, Soc, 106.3374 (1984
): J.

Mo1. Cat, 32.357 (1985): 31.
217 (1985)), oxidation method with peroxide (
J. Org. Chem., 40, 1998 (1975)
:4(1,1860(1975) :42,2077
(1977)) are known. However, these methods are difficult to implement industrially because they may need to be carried out in an anhydrous system or require a stoichiometric amount or more of the N-oxyl compound.

In addition, for the purpose of improving these methods, a method using sodium hypochlorite as an oxidizing agent (J, Org.

Chea+, 52.2559<1987)) has been developed. According to this method, a catalytic amount of the N-oxyl compound is used, and the nitrosonium salt is continuously generated so as to be recycled. However, since this method also requires a large amount of sodium hypochlorite, the following problems arise when it is carried out on an industrial scale.

In other words, because sodium hypochlorite is unstable at high concentrations, only about 12
% concentration product, and if more than the equivalent amount of sodium hypochlorite is used, the number of reaction liquid ports will increase, resulting in a decrease in production efficiency and an increase in waste liquid, which is economically disadvantageous.

Another method is to directly electrolytically oxidize an N-oxyl compound to produce a nitrosonium salt, and use this salt as an oxidizing agent to oxidize a secondary alcohol to the corresponding ketone (J
, Am, CherA, Soc, , 105°4492
(1983)). This method does not require a chemical oxidizing agent, but the N-oxyl compound is used in twice the molar amount relative to the secondary alcohol, and the preparation of the nitrosonium salt by electrolytic oxidation is carried out in a separate reactor from the oxidation of the alcohol. This is the so-called Excel method (Ex-Cel I Method), which is disadvantageous for industrial implementation because it requires a structurally complicated separation cell for the electrolyzer.

[Problems to be Solved by the Invention] The present inventors have conducted intensive research in view of the above-mentioned prior art, and have found that the oxidation of N-oxyl compounds to nitrosonium salts by electrolysis and the oxidation of secondary The oxidation of the alcohol to the corresponding ketone can be carried out in a single electrolytic cell, and the regeneration of the nitrosonium salt and the oxidation of the alcohol can be carried out continuously using an N-oxyl compound as a catalyst. For the first time, he discovered a completely new method for producing ketones with high yield and high current efficiency, leading to the completion of the present invention.

[Means for Solving the Problems] That is, the present invention relates to a method for oxidizing a secondary alcohol to a ketone, which is characterized by electrolyzing the secondary alcohol together with an N-oxyl compound.

[Operations and Examples] In the method of the present invention for producing ketones by oxidizing secondary alcohols using a nitrosonium salt, an electrolytic solution containing a secondary alcohol and an N-oxyl compound is electrolyzed, and first, Generates nitrosonium salt. This compound immediately oxidizes the secondary alcohol to a ketone and returns to the original N-oxyl compound, but is again converted into a nitrosonium salt by electrolytic reaction. Therefore, the nitrosonium salt is recycled in the method of the invention.

In the present invention, since the catalytic oxidation of alcohol and the regeneration of the catalyst by electrolytic oxidation are carried out continuously in the same electrolytic cell, a non-diaphragm type electrolytic cell with the simplest structure can be used.

In the present invention, the electrolytic solution used is, for example, a two-phase solution consisting of water and a hydrophobic solvent, a homogeneous solution containing water, or a mixed solution consisting of the homogeneous water solution and a hydrophilic solvent, and the aqueous layer is preliminarily treated with a halogen-containing compound. is dissolved.

Here, the halogen-containing compound referred to in this specification refers to a compound that generates halogen ions in water. By inserting an electrode into this electrolytic solution and electrolyzing it, an active halogen compound is created from halogen ions, and this is the same as the active halogen compound. A nitrosonium salt is generated by acting on the N-oxyl compound contained in the electrolytic cell. The generated nitrosonium salt oxidizes the secondary alcohol to a ketone and returns itself to an N-oxyl compound, but the N-oxyl compound is oxidized again to an oxonium salt by the active nitrogen compound generated in the electrolytic reaction. Repeat the process of
In the end, the N-oxyl compound is recycled as an oxidizing agent for converting secondary alcohols into ketones. The diagram is as follows.

(In the formula, X represents P, CI, B "or 1.") When carrying out the present invention, the raw material is additionally supplied while the product is removed from the reaction system not only in a batch system but also in a continuous system.
It is also possible to use so-called continuous tank reactor systems.

In the method of the present invention, electrolysis can be carried out using a non-diaphragm type electrolytic cell which is simple in terms of equipment, so a continuous reaction process is also possible, and the method is industrially advantageous.

The secondary alcohol used in the method of the invention has the general formula RI R2Cll0I! (where R1 and R
2 represents an alkyl group having 1 to 50 carbon atoms, respectively), and such secondary alcohols are, for example, chain or cyclic compounds that have a secondary hydroxyl group, and have compounds in the molecule that are resistant to oxidation of nitrosonium salts. It may have a functional group such as ketone, ester, amide, nitro, nitrile, halogen, sulfonyl, olefin, phenyl, etc., which is stable.

Such a secondary alcohol may have two or more secondary hydroxyl groups in the molecule, and in this case, it is converted to a di(poly)ketone via a monoketone. Also, 1 in the same molecule
If there is a class hydroxyl group, the ke! - Converted to aldehyde. Examples of such secondary alcohols include 2-pentanol and 3-pentanol.
-Pentanol, 2-hexanol, 3-hexanol, 2-heptatool, 2-octatool, 3-octatool, 3-decanol, ■, 10-undecanediol, α-phenethyl alcohol, ■, 1-dichloro- 2-heptatool, ■-phenyl-1-propatool, ■-methylsulfonyl-2-octatool, 2-nitro-3-
Nonyl alcohol, 1-carboethoxyamino-2-
Property Tools, L, 1, 1. -Trichloro-2-octatool, 1.1-dichloro2-octatool, 1.3
Aliphatic and aromatic alcohols such as -dichloro-2-propanol; cyclopentanol, cyclohexanol, 4-tert.
-Methylcyclohexanol,! Examples include alicyclic alcohols such as menthol, cycloheptatool, cyclooctatool O1l cyclododecanol, and 1,4-cyclohexanediol, but the present invention is not limited to these examples.

The N-oxyl compound used has the general formula (I): (wherein, R3, R4, Rs R6, R7 and R8 are each an alkyl group having 1 to 30 carbon atoms, and R3 and 86 are bonded to form a cyclic compound. In that case, there may be an unsaturated bond within the ring.Also, a functional group such as an amino group, carbonyl group, amide group, halogen, or nitrile may be bonded to the carbon forming the ring. Moyo (, 2 in the molecule
(which may have more than one N-okynyl group) can be mentioned. Specific examples of such N-oxyl compounds include 2,2゜4,4-tetramethylazetidine-1-oxyl, 2゜2-dimethyl-4,
4-dipropylacetidine-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-viroline-1-oxyl-
3-carboxylic acid, 4-amino-2,2,8.6-tetramethylbiperidine-1-oxyl, 4-oxo-2,
2,6,B-tetramethylpiperidine-1-oxyl,
4-Methoxy-2,2,8,6-titramethylpiveridine-1-oxyl, 4-benzoyloxy-2,2°C
16-tetramethylpiperidine-1-oxyl, 2゜2
, (i, 6-titramethylpiveridine-1-oxyl 4
-carboxylic acid, 4-hydroxy-2,213,6-titramethylpiveridine-l-oxyl, 4-cyano-2
゜2.6.8-Tetramethylpiperidine-1-oxyl, di-t-butylamine-〇-oxyl, general formula = R9
000(CH2)8 CO2R9 C)+3 General formula: CH2-CHCHCH2 CO2RI CO2R9CO2R9CO2R9 (in the formula, R9 is the same as above), and the like.

Use of these N-oxyl compounds as catalysts is 2
0.0 (101 to 10 mol, preferably 0.03 to 0.5 mol) per 1 mol of alcohol.

If the amount is less than o, ooi mole, the yield will decrease and 1
Even if it is used in an amount greater than 0 mol, no further improvement in effect can be expected and it is uneconomical.

Examples of halogen-containing compounds include fluorine, chlorine,
Examples include alkali metal salts such as bromine and iodine, alkaline earth metal salts, ammonium salts, transition metal salts, and hydrogen halides.

Specific examples of such halogen-containing compounds include lithium chloride, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, strontium chloride, barium chloride, aluminum chloride, zinc chloride, tin chloride,
Chlorides such as nickel chloride, cobalt chloride, and ammonium chloride; Bromides such as lithium bromide, sodium bromide, potassium bromide, magnesium bromide, calcium bromide, zinc bromide, and ammonium bromide; hydrobromic acid, etc. Examples include hydrohalic acid. Among these halogen dowel compounds, bromides are particularly preferred in terms of efficiently obtaining ketones. The concentration of the halogen-containing compound in the aqueous solution of the halogen dowel compound ranges from Q, F type % to a saturated aqueous solution, preferably from 5% by weight to a saturated aqueous solution.

At concentrations lower than 0.1 m2%, the reaction tends to be slow.

911 in the aqueous solution is 1-13, preferably 4-12. If the pH is less than 2111, the reaction is slow, and if the pH exceeds 3, the product tends to be unstable and the yield tends to decrease.

If the reaction substrate, the secondary alcohol, is water-soluble, the reaction can be carried out in an aqueous solution, but generally a two-phase system consisting of a hydrophobic organic solvent and an aqueous solution containing a halogen-containing compound is used. or in a mixed solution of an aqueous solution containing halogen ions and a hydrophilic organic solvent. The organic solvent may be any organic solvent that is stable against oxidation of the nitrosonium salt, and specific examples of such organic solvents include ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and 3-pentanone; acetonitrile, and propion. Nitriles such as nitrile and benzonitrile; halogenated hydrocarbons such as carbon ditetrachloride, chloroform, methylene chloride, dichloroethane, trichloroethane, and chlorobenzene; aliphatic or cycloaliphatic such as pentane, hexane, cyclohexane, heptane, octane, and cyclooctane; Hydrocarbons: Aromatic hydrocarbons such as benzene, toluene, xylene, and ethylbenzene; Esters such as methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate, methyl propionate, and γ-butyrolactone; Ethers such as tetrahydrofuran, dimethoxyethane, and dioxane ;Other examples include sulfolane. These organic solvents may be used alone or as a mixed solvent of two or more.

In addition, when using a heterogeneous solution consisting of water and a hydrophobic organic solvent, it is preferable to perform sufficient stirring to carry out the reaction smoothly.

Although electrodes used in ordinary electrolytic reactions can be used as the electrodes, the present invention is not particularly limited by the type of such electrodes.

Specific examples of such electrodes include platinum, platinum black, carbon, titanium, stainless steel, nickel, lead oxide, and other electrodes that have been subjected to surface treatment, etc., and the anode and cathode may be made of the same material or Different materials are used.

The electrolytic cell may be either an electrolytic cell in which the anode and cathode chambers are separated by a diaphragm or a non-diaphragm electrolytic cell, but a non-diaphragm electrolytic cell is usually used.

The current density is determined by inserting an electrode into an electrolytic bath containing a secondary alcohol, an aqueous solution containing a catalyst N-oxyl compound, and a halogen ion, and a solvent, and increasing the current density to 0.
001 to IOA/c-, preferably 0.01 to 0
．． It is adjusted to be in the range of 2A/cd. When the current density is lower than 0.0'01A/cd, the reaction takes a long time, and when it is higher than IOA/cd, high voltage is required and side reactions tend to increase. .

In the present invention, the amount of electricity required for the reaction is theoretically 2 faradays per equivalent of hydroxyl group, but in order to complete the reaction, it is desirably 2 to 10 faradays, preferably 2 to 6 faradays. .

The reaction temperature ranges from -20 to 100°C, preferably -100°C.
~50°C. If the reaction temperature is lower than -20°C, the reaction will be slow, and if it is higher than 100°C, side reactions will occur and the yield will tend to decrease.

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

After the reaction is completed, the hydrophobic solvent is separated and the solvent is distilled off to obtain a crude product. Distillation, if necessary;
The corresponding ketone body can be obtained by conventional post-treatment methods such as recrystallization and chromatographic purification.

Next, the present invention will be explained in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 4-t-butylcyclohexanol 15B, 3 mg (1.0 mmol), 2.8 mg of 4-benzoyloxy-2,2,6,6-titramethylpiberidine-1-oxyl in a 20 ml glass reaction vessel. (0.01 mmol),
Weigh out 3 ml of methylene chloride and 5 ml of a 25% sodium bromide aqueous solution saturated with sodium bicarbonate, insert two platinum electrodes (surface area of each 1.5 cd) into this mixture, and measure the current value at room temperature while stirring. Constant current electrolysis was performed at 30 mA.

2.6 1 mole of Farade was energized through the electric port to initiate the reaction.
L L, separating the methylene chloride layer and the aqueous layer of the reaction mixture;
The aqueous layer was extracted with methylene chloride. The methylene chloride extracts were combined and concentrated, and the remaining liquid was purified by eluting with a mixed solvent of n-hexane-ethyl acetate (10:l) on a silica gel column, and purified with 4-t-butylcyclohexanone 143. I got .5mg.

In addition, an absorption peak at 1720 cm-' was observed in the IR spectrum, confirming the presence of C--O. The yield was 93% and the current efficiency was 67%.

N1 of 4-t-butylcyclohexanone obtained below
The M1 constant results of the 4R spectrum are shown.

(NMR spectrum (60M1lz (CDCIs))
, unit: ppm (TMS)) 60.69 (s, 9H, t-Bu) IJO ~ 2.50 (m, 911) Examples 2 to 6 4-benzoyloxy-2,2 used in Example 1
, G, using the N-oxyl compounds shown in Table 1 instead of G-tetramethylpiperidine-1-oxyl,
The reaction was carried out in the same manner as in Example 1, except that electricity was applied until the reaction was completed, and 4-1-butylcyclohexane was obtained. Furthermore, I
The R spectrum confirmed the presence of an absorption peak at 1720 cm-'. Obtained 4-
The yield of 1-butylcyclohexanone is also shown in Table 1.

[Margin below] Examples 7 to 9 4-benzoyloxy-2,2゜6. used in Example 1.
4-t was prepared in the same manner as in Example 1, except that the addition of 6-titramethylpiveridine-1-oxyl was adjusted as shown in Table 2, and an electric current of 1 mole of 2.0 farade was applied. −
Butylcyclohexanone was obtained. The yield of the 4-1-butylcyclohexanone obtained is shown in Table 2.

Table 2 Examples 10 to 12 Instead of the 25% sodium bromide aqueous solution (pits 8 to 9) saturated with sodium bicarbonate used in Example 1, saturated baking soda having the sodium bromide concentration shown in Table 3 was used. The procedure was carried out in the same manner as in Example 1, except that an aqueous solution of 1 mole of 2 Farade was applied, and 4-t-butylcyclohexanone was obtained. The yield of the 4-t-butylcyclohexanone obtained is shown in Table 3.

Examples 13 to 18 Examples except that instead of the 25% sodium bromide aqueous solution saturated with sodium bicarbonate used in Example 1, an aqueous solution saturated with sodium bicarbonate having the halogen-containing compound concentration shown in Table 4 was used. The amount of electricity shown in Table 4 was applied in the same manner as in 1 to obtain 4-t-butylcyclohexanone. The yield is also shown in Table 4.

Table 4 Table 3 Examples 19 and 20 The same procedure as Example 1 was carried out except that the electrodes shown in Table 5 were used in place of the platinum plate used in Example 1, and 4-t-butylcyclohexanone I got it.

The yield is also shown in Table 5.

Ta. The yield of the obtained 4-t-butylcyclohexanone is also shown in Table 6.

[Margin below] Table 5 Examples 21 to 29 Examples except that the organic solvent shown in Table 6 was used instead of the methylene chloride used in Example 1, and the amount of electricity was adjusted as shown in Table 6. Electricity was applied in the same manner as in 1 to obtain 4-1-butylcyclohexanone using 1 mole of 1 mol of Farade as shown in Table 6. The products shown in Table 7 were obtained. The yield of the obtained product is also listed in Table 7.

[Margins below] Examples 30 to 37 Electrical ff12,0 in the same manner as in Example 1 except that the secondary alcohol shown in Table 7 was used instead of 4-t-butyrunclohexanol used in Example 1. ~In addition, Example 30
NMR spectrum of the product obtained in ~37 (60MH
z (CDC&3>, units: ppc (TMS)) and IR spectra are as follows.

(Example 30; Cyclooctanone) (A) NMR spectrum δ 1.20-2.05 (m, IOH, -C
)+2- )2.41 (+1.4H1-CH2-)
(B) IR spectrum 1710 cm-' absorption (N C-0) (Example 31; 2-octanone) (A) NMR spectrum δ 0.89 (m, 3H, -C) 13) 1.28 ~
L, [io (11,8)1. -CH2-)2.14
(s, 3H, -CH3) 2.42 (t, 2H, -CH2-) (B) IR spectrum 1715 cm-1 absorption (n C-0) (Example 32; 3-decanone) (A) NMR spectrum 60 .89 (fll, 3tL-CH3)1.05
(s, 311, -CH5) 1.28-1.80
(m, IOH, -CH2-)2,38 (q,
2 Hl-CH2-)2.42 (q, 2H, -C
H2-) (B) IR spectrum 1715 cm-' absorption (Example 33. 10-ketoundecanal) (A)
NMR spectrum δ 1.20-1.80 (brd, 1211, -
CH2-)2.10 (S, 3H, -CH5) 2.30-2.55 (a+, 4H, -CH2-)9
．． 64 (III, -CHO) (B) IR spectrum 1720 cm absorption (;co> (Example 34; 4-hydroxyclohexanone) (A
) NMR spectrum 61.82-2.92 (m, 91]) 4.06-4.
38 (m, 1ll) (B) IR spectrum 1700ca+-' absorption (N C-0), (Example 35; 1,1-dichloro-2-heptanone) (A) NMR spectrum 60.89 (3H1-CH3) ■, 15-1.75 (Ill, 811, -CH2-)
2.79 (t, 21i, -C)12-)5.75
(s, 11(,-011(J2)(B) IR spectrum 1735ca+-1 absorption<n c-o>(A) NMR
Spectrum 60.82 (s, 3H, -CH3) 0.90 (s
, 3H,-C)13)0.95 (s, 3H,-
CH3) 1.20-2.30 (m, -CH2-:;CI-)(
B) IR spectrum 1725 cm-' absorption <;c-o> Comparative example 1 4-benzoyloxy-2,2°6. used in Example 1.
The same procedure as in Example 1 was carried out except that 6-tetramethylpiperidine-1-oxyl was not added, and 4-
No t-butylcyclohexanone was produced.

Comparative Example 2 4-benzoyloxy-2,2゜6. used in Example 1.
The same procedure as in Example 1 was carried out, except that 2.6 mg of 2.2,8.6-tetramethyl-4-penzoyloxyviveridine was used instead of 6-titramethylpiveridine-1-oxyl. No 4-t-butylcyclohexanone was produced.

Comparative Example 3 The same procedure as in Example 1 was carried out except that a 5% aqueous lithium perchlorate solution saturated with baking soda was used instead of the 25% aqueous sodium bromide solution saturated with baking soda used in Example 1. 4-1-Butylcyclohexanone was obtained in a yield of 5% by applying a current of 1 mole of 2,0 farade.

[Effects of the Invention] According to the method of the present invention, the oxidation of an N-oxyl compound to a nitrosonium salt by electrolysis and the oxidation of the nitrosonium salt to a ketone corresponding to a secondary alcohol can be carried out in a single electrolytic cell. Furthermore, the N-oxyl compound can be used as a catalyst to continuously regenerate the nitrosonium salt and oxidize the alcohol, making it possible to produce ketones industrially with high yield and high current efficiency. Ru.

Claims (1)

[Scope of Claims] 1. A method for oxidizing a secondary alcohol to a ketone, which comprises electrolyzing the secondary alcohol together with an N-oxyl compound. 2. The oxidation method according to claim 1, wherein an aqueous solution of a halogen-containing compound is used as the electrolyte.