JPH02200653A - Preparation of aldehyde from primary alcohol - Google Patents

Abstract

PURPOSE:To profitably provide the subject compound in a high yield without causing a problem such as the treatment of waste water by treating a primary alcohol with a bromous acid alkali metal salt in the presence of a catalytic amount of an N-oxyl compound. CONSTITUTION:A primary alcohol is reacted with a bromous acid alkali metal salt (e.g. potassium bromite or sodium bromite), preferably in a ratio of 1:1-10mol, especially 1:2-6mol, at -20 to 100 deg.C, especially -10 to 50 deg.C, in the presence of a catalytic amount of an N-oxyl compound to provide the objective compound. The N-oxyl compound is concretely 2,2,4,4-tetramethylazetidine-1-oxyl; 2,2-dimethyl-4,4-dipropyl azetidine-1-oxyl; etc., and is preferably used in an amount of 0.003-0.5mol per mol of the primary alcohol.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for producing aldehydes from primary alcohols, which can obtain aldehydes from primary alcohols in high yield.

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

Various methods have been developed to obtain aldehydes by oxidizing primary alcohols. For example, manganese dioxide, manganese dioxide, and
Methods using heavy metal oxides such as chromic acid and lead tetraacetate require stoichiometric or higher amounts of toxic oxidizing agents, leaving problems in the disposal of waste after the reaction. .

Another method using a stoichiometric amount of an oxidizing agent is a method using hydrogen peroxide-metal salt (Can.

J, Chea, 48.2924 (19B5)), DM
Method using SO (dimethyl sulfoxide) (CheI
I, Ber, 100.8881 (1967)), the method using iron N potassium (J, Am.

CheIIl, Soc, 80.2038 (195B
)), method using nickel peroxide (J, Org, Ch
em, 27.1597 (19B2)), method using ruthenium complex (Tetrahedron Letter
s, 22.1605 (1981)), method using hypochlorous acid (Tetrahedron Letters, 1
641 (197B)), but all of these methods generally require complicated reaction operations, so there are many problems in implementing them industrially.

In addition to these methods, there is also an air oxidation method using noble metals as a catalyst, such as a method using platinum black (Tetr
ahedron, 9.67 (1960)) and a method using palladium salt (Tetrahedron, 9.67 (1960)).
(1980)), but all of these methods generally require conditions of high temperature and pressure, making them unsuitable for the synthesis of aldehydes, and using expensive precious metals, making them economically disadvantageous. be.

A method of oxidizing primary alcohols to aldehydes under relatively mild conditions using nitrosonium salts as catalysts has also been developed. Such oxidation methods include, for example, a method in which a halogen such as bromine or chlorine is used as an oxidizing agent to generate a nitrosonium salt from an N-oxyl compound (J, AIl
, Che+a.

Soc,, 106.3877 (19B4), J, Org.
, Chem, 50.3930 (1965)), copper,
Method using metal compounds such as iron (J, Am, Chen
+, Soc,, 106.3374 (1984), J.
Mol.

Cat, 32,357 (19g5) and 31.2
17 (1985)), peroxide oxidation method (J, Or
g, Che [1,, 40, 1988 (1975), 40
．． 1880 (1975) and 42.2077 (19
77)) are known. However, these methods are difficult to implement industrially because they need to be carried out in an anhydrous system or require a large amount of N-oxyl compound.

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

Chem, 52.2559 (1987)) has been developed. In this method, an N-oxyl compound is used in a catalytic amount, and the nitrosonium salt is continuously generated so that it can be recycled.

However, when this method is implemented on an industrial scale, the following problems arise. In other words, sodium hypochlorite is an unstable compound and is difficult to store and handle, especially at high concentrations.Sodium hypochlorite is generally available and handled in the form of aqueous crystals with a concentration of about 12%, and the stoichiometric amount is If more than the stoichiometric amount of the aqueous sodium hypochlorite solution is not used, the amount of reaction solution will increase, leading to a decrease in production efficiency, an increase in waste solution, and other problems, such as being economically disadvantageous.

In addition, there is a method in which an N-oxyl compound is electrolytically oxidized by a direct method to produce a nitrosonium salt, and this salt is used as an oxidizing agent to oxidize a primary alcohol to an aldehyde corresponding to the primary alcohol (J, AIl ,Chem,So
c,, 105.4492(In2)). This method does not require a chemical oxidizing agent, but uses twice the molar amount of the N-oxyl compound relative to the primary alcohol, and the preparation of the nitrosonium salt by electrolytic oxidation is performed in a separate reactor from the oxidation of the alcohol. The so-called Excel method (Ex-Cel)
1 M'method), and has drawbacks such as requiring a structurally complex separation cell for the electrolyzer, which is disadvantageous for industrial implementation.

[Problems to be Solved by the Invention] Therefore, in view of the above-mentioned prior art, the present inventors have conducted intensive research to find a method for industrially obtaining aldehydes from primary alcohols in high yield. It has been discovered that the corresponding aldehyde can be obtained in high yield from a primary alcohol by treating the primary alcohol with an alkali metal bromite in the presence of a certain amount of N-oxyl compound, and the present invention was completed.

[Means for Solving the Problems] That is, the present invention relates to a method for producing an aldehyde from a primary alcohol, which is characterized by reacting the primary alcohol with an alkali metal bromite salt in the presence of an N-oxyl compound.

[Function and Examples] In the method of the present invention for producing aldehyde by oxidizing a primary alcohol in the presence of an N-oxyl compound using an alkali metal salt of bromite, the effect of the alkali metal salt of bromite is A nitrosonium salt is produced from the N-oxyl compound.

This compound immediately oxidizes the primary alcohol to an aldehyde and returns to the original N-oxyl compound, but is again converted to a nitrosonium salt by the alkali metal bromite salt in the system, and is converted back into the primary alcohol. Acts as an oxidizing agent to aldehydes.

Therefore, the nitrosonium salt is recycled in the method of the invention.

The primary alcohol used in the method of the present invention is, for example, a linear alcohol having a primary hydroxyl group represented by RCH20H (in the formula, R represents a hydrogen atom or an alkyl group having 1 to 50 carbon atoms). or cyclic compounds, and the molecules of such primary alcohols contain functional groups such as ketones, esters, amides, nitro, nitriles, halogens, sulfonyls, olefins, and phenyls that are stable against oxidation of nitrosonium salts. It may be Further, the primary alcohol may have two or more primary hydroxyl groups in the molecule, and in this case, it is converted to di(poly)aldehyde via monoaldehyde. If there is a secondary hydroxyl group in the same molecule, it is converted to ketoaldehyde via hydroxyaldehyde. Said 1
Specific examples of alcohols include 1-propanol, l-pentanol, ■-hexanol, ■-octatool, l-decanol, ■-undecanol, heptadecanol, cyclohexylmethylcarbinol, benzyl alcohol, and β-phenethyl alcohol. , 2-ethylhexanol, tetrazocar 2-ynyniol, 1
．． 8-octanediol, ■, 10-decanediol,
Cyclohexanedimethylcarbinol, l-methylsulfonyl-1-octatool, 2-nitro-1-decyl alcohol, 4-ethoxycarbonyl-1-butanol,
Heptadecafluoro, however, the present invention is not limited to such examples.

In the present invention, the N-oxyl compound used is represented by the general formula (I): (wherein, RI R2R3R4R5 and R6 each independently represent an alkyl group having 1 to 30 carbon atoms, and R1
and R4 may be combined to form a cyclic compound, and in this case, the ring may have an unsaturated bond. Further, 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, and the molecule may have two or more N-oxyl groups. ) can be mentioned. Specific examples of such N-oxyl compounds include 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-8-pyrroline-1-oxyl-3-carboxylic acid, 4-amino-2゜2.8.6-tetramethylpiperidine-1-oxyl, 4-oxo-2
,2,8,8-tetramethylpiperidine-loxyl,
4-methoxy-2,2,B, 8-tetramethylpiperidine-1-oxyl, 4-benzoyloxy-2,2,8
, 8-tetramethylpiperidine-1-oxyl, 2.2
．． 8.8-Tetramethylpiperidine-1-oxyl-4
-carboxylic acid, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-cyano-2,2
,8,6-tetramethylpiperidine-1-oxyl, di-t-butylamine-N-oxyl, membrane pair 2R'0CO
(CH2) s CO2R' (in the formula, R7 represents)
, -membrane pair: (in the formula, R7 is the same as above), and the like.

The amount of these N-oxyl compounds used as a catalyst is 1
alcohol 1 o, oooi to n+ol ~ 10
mols is preferably 0.003 to 0.5 mol.

If it is less than (1,Hl)Imol, the yield will decrease, and if it is more than 10 mol, no improvement in the effect can be expected even if a larger amount is used, and it will become uneconomical.

The alkali metal salt of bromite used in the present invention includes:
Examples include potassium bromite, sodium bromite, and the like, which are used as anhydrides, hydrates, or aqueous solutions. Industrially, it is preferable to use, for example, a commercially available aqueous sodium bromite solution used as a desizing agent. The amount of these alkali metal bromite salts to be used as an oxidizing agent is 1 to 10 m011, preferably 2 to 611 mol, per 1 mol of primary alcohol. If the amount is less than 1 mol, the reaction will not be completed, and if it is used in an amount greater than 1 mol, no further improvement in effect can be expected, resulting in uneconomical results.

The reaction can be carried out in an aqueous solution if the primary alcohol that is the reaction substrate is water-soluble; however, it is generally carried out in a heterogeneous mixed solution consisting of a two-phase system of a hydrophobic organic solvent and water or in water. It may be carried out in a mixed solution of 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;
Nitriles such as acetonitrile, propionitrile, benzonitrile; halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride, dichloroethane, trichloroethane, chlorobenzene; pentane, hexane,
Aliphatic or alicyclic hydrocarbons such as cyclohexane, heptane, octane, and cyclooctane; Aromatic hydrocarbons such as benzene, toluene, xylene, and ethylbenzene; Methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate, and methyl propionate and γ-butyrolactone; ethers such as tetrahydrofuran, dimethoxyethane, and dioxane; and 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 carry out the reaction smoothly by stirring sufficiently.

Note that the concentration of the primary alcohol in the solvent solution is not particularly limited, but it is usually
It is preferably 1 to 50% by weight, especially 0.1 to 80% by weight.

Further, it is desirable that the pH of the aqueous solution or aqueous layer is 4 to 12, preferably 6 to 11. When the pH is less than 4, the amount of esters (dimerized products) produced due to side reactions increases and the yield of aldehyde decreases, and when the pH exceeds 12, side reactions occur from the generated aldehydes and the yield decreases. There is a tendency to

The reaction is started by mixing the primary alcohol solvent solution, the N-oxyl compound, and the alkali metal bromite salt, and the reaction temperature is in the range of -20 to 100°C.
Preferably, the temperature is in the range of -10 to 50°C.

If the reaction temperature is lower than 20°C, the reaction rate will be slow, and if it is higher than 100°C, side reactions will occur and the yield will tend to decrease.

The reaction may be carried out until the primary alcohol in the system disappears, and usually requires about 1 to 10 hours.

After the reaction is completed, the hydrophobic solvent is separated and the solvent is distilled off to obtain a crude product. Distillation, if necessary;
By performing conventional post-treatments such as recrystallization and chromatographic purification, the aldehyde corresponding to the primary alcohol can be converted.

Next, the present invention will be explained in more detail based on Examples, but the present invention is not limited to these Examples.

Run N1 1.7 1-undecanol in a N15O glass reaction vessel
2 g (lomlIlol), 28 mg (0,1 nvol) of 4-benzoyloxy-2,2゜6.6-tetramethylpiperidine-1-oxyl, 10 ml of methylene chloride and to keep p)I in the aqueous layer at 9. Baking soda 5%
Weigh out 20 ml of an aqueous solution containing , cool it in a water bath, and while stirring, add 6.1 g of sodium bromite trihydrate (manufactured by Nihon Shirikani Gyogyo ■, containing 65% NaBr02).
(30 mmol) was added. pH of the water layer at this time
was 9. Thereafter, the reaction was carried out at room temperature for 3 hours.

After confirming the disappearance of the raw material primary alcohol by thin layer chromatography (TLC), 10 ml of 5% sodium hydrosulfide was added and thoroughly stirred to inactivate unreacted excess sodium bromite. The reaction mixture was separated into a methylene chloride layer and an aqueous layer, and the aqueous layer was extracted with methylene chloride. The methylene chloride extracts were combined and concentrated, and the remaining liquid was purified on a silica gel column by elution with a mixed solvent of n-hexane ethyl acetate (7:1) (volume ratio) to obtain 1-undecanal 1. 88 g was obtained (yield: 99%).

In addition, 1792 cm −' (n
eat), 'H-NMR (CDCfs, 500MHz
), δ9. A peak was observed at yeppm(t),
The presence of aldehydes was confirmed. The results of the IH-NMR spectrum of 1-undecanol obtained below are shown.

(1) 1-NMR (CDCfs, 500MHz) δ
ppm) 0.88 [(t),3H,-CH3]1.
28 [(m), 14H, -(CH2)7]1.62
[(ffl), 2H], 2.41 [(m), 2H]
9.76 [(t) , IH, -CHO] Examples 2 to 5 4-benzoyloxy-2,2 used in Example 1
, 8,8-tetramethylpiperidine-1-oxyl, the N-oxyl compound shown in Table 1 (0,1■o
The reaction was carried out in the same manner as in Example 1, except that 1) was used and the reaction was completed by adding the amount of sodium bromite necessary to complete the reaction. The yield of l-undecanal obtained is also shown in Table 1.

[Margin below] Examples 6 to 8 In Example 1, 4-benzoyloxy-2,2゜6
．． The reaction was carried out in the same manner as in Example 1, except that the amount of 6-tetramethylpiperidine-l-oxyl added was changed as shown in Table 2, and sodium bromite tridisperse hydrate (80mlol) was added. l-undecanal was obtained. Table 2 shows the yield of niundecanal obtained.

Table 2 Examples 9 to 16 Instead of the methylene chloride used in Example 1, the organic solvent (10 ml) shown in Table 3 was used, and sodium bromite trihydrate was used as shown in Table 3. The same procedure as in Example 1 was carried out except for the following.

The yield of 1-undecanal obtained is shown in Table 3.

[Examples 17 to 22 Below are blank spaces. In place of l-undecanol used in Example 1, primary alcohols shown in Table 4 were used, and sodium bromite trihydrate was used in the amounts shown in Table 4. The same procedure as in Example 1 was carried out except that the aldehydes shown in Table 4 were obtained. The yield of the aldehyde obtained is also shown in Table 4.

Margin below C: IH-NM of the products obtained in Examples 17 to 24
R spectrum (CDC#3, 500MHz, δp
p11) was as follows.

(Example 17; n-octanal) 1) 1-NMR spectrum 0.87 (m, 3H1-〇)+3) 1.29 (m
, 101 , -(CH2)6-)2.41 (+
a, 2H, -CH2-)9.85 (t, t■, -
C) TO) (Example 18; n-dodecanal) IH-NMR spectrum 0.88 (t, 3H, -CH5) 1.28 (1,18H, -(CH2)9-) 2.40
(1,2H,-C)12-)9.65 (tStH,
-CHo) (Example 19; n-octadecanal) IH-NMR spectrum 0.87 (m, 38.-CH3) 1.24 (m, 80B, -(CH2)+6-)
2, H (m, 2H, -CH2-) 9, ffO (t, LH, -CHO) IH-NMR spectrum 1.13 (d, 311, -CH5) 1.59 (i
Sloll, -(CI2)5-)2.04 (s,
ill, -〇H) 2.43 (+a, ill, -CIl(C113)
-)9.83 (d, 11L -CHO) (Example 21; △ bar ψφ-= -CIIO) IH-NM
R spectrum 0.87 (t, 3H, -CHg) 1.1-1.8
(+n, 18H, -CH2)9-)2.37 (t
, 2H,-C)+2-)9.17 (tSIHl-C
HO) (Example 22; Benzaldehyde) 1) (-NMR spectrum 7.2-7.9 (m, 5HSPh-) 9.87 (S, ill, -CHO) (Example 23;
2-phenylacetaldehyde) IH-NMR spectrum 3.6 (d, 2H, -〇H2-) 7.18 (s, 5HSPh-) 9.8 (tSIH, -CHO) (Example 24; 3-phenylpropionaldehyde )!
) 1-NMR spectrum 2.8 (+n, 4H, -(CH2)2-) 7.1 (s,
5H, Ph-) 9.82 (t, IHSCHO) Comparative Example 1 2,2.8.8-tetramethyl-4- used in Example 1
The reaction was carried out in the same manner as in Example 1 except that benzoyloxypiperidine-1-oxyl was not added, and the reaction was carried out for 18 hours. ■-Undecanal was produced in a yield of ■8%, and 88% of 1- Undecanol was recovered.

[Effects of the Invention] According to the method of the present invention, the corresponding aldehyde is removed from the primary alcohol by reacting an alkali metal bromite salt with the primary alcohol in the presence of a catalytic amount of an N-oxyl compound. The effect is that it can be easily obtained industrially in high yield.

Claims (1)

[Claims] 1. 1 characterized by reacting a primary alcohol with an alkali metal bromite salt in the presence of an N-oxyl compound
A method for producing aldehydes from alcohols.