JPS6021970B2 - Novel production method for α-keto acids - Google Patents

Description

[Detailed description of the invention] The present invention relates to a novel method for producing Q-keto acids.

More specifically, the present invention relates to a novel method for producing carbonyl compounds by oxidizing quaternary salts. The Q-keto acids obtained by the present invention are useful as pharmaceuticals or industrial chemicals, and are also useful as intermediates thereof. No method of producing Q-keto acids by the method of the present invention has hitherto been known.

Since the present invention binds the target Q-keto acids in good yield under mild conditions, it has become possible to synthesize Q-keto acids, which were difficult to synthesize in the past, by applying the present invention. This is a valuable method for producing Q-keto acids. As a result of extensive research into a new method for producing carbonyl compounds, the present inventors have discovered a method in which a quaternary salt (on the n-B side) is irradiated with light in the coexistence of 4N11- (Bu represents a butyl group). It was discovered that a carbonyl compound can be obtained by oxidizing with oxygen, and based on this knowledge, the present invention was completed.

The present invention relates to the general formula '1) [in the formula '11, R, ' is an alkyl group, an aralkyl group, R2 is an alkyl group, an aralkyl group, a phenyl group, an aromatic double ring or an alkoxycarbonyl alkyl group, and A ↓ or (R3, R4 represent a hydrogen atom or an alkyl group, R5 represents an alkyl group), X- represents a halogen ion. The general formula ■ (R in formula '21) is oxidized with oxygen under light irradiation in the presence of
R2 has the same meaning as above)
The present invention provides a novel method for producing keto acids.

The quaternary salt represented by the general formula '1' used as a raw material in the present invention can be synthesized by a known method from the corresponding a-halokacarbonyl humble conductor and pyridines or N-alkyl a-thiopyridones.

R and R2 of the above quaternary salt are not particularly limited in the number of carbon atoms or structure within the above-mentioned range, and R3 and R4 are hydrogen atoms or alkyl groups, and the alkyl group is C
, ~C3 are preferred. R5 is an alkyl group, and C, to C3 are particularly preferred. X- is a bromide ion or an iodo ion. Examples of suitable quaternary salts are shown below. The method of the present invention is illustrated by the following reaction formula.

(In the formula, R,, R2, A+, and X- have the same meanings as above.) The method of the present invention is carried out by oxidizing the above-mentioned quaternary salt in an inert solvent.

Furthermore, the method of the present invention optionally contains the above-mentioned quaternary salt in an inert solvent (Bu represents a butyl group).
An overall improvement in yield is observed by oxidation with oxygen in the presence of light irradiation.

Specifically, when X- is a promyeon, (nBu)4
The coexistence of N11- is preferable, and when X- is an iodide ion, the coexistence effect of (u)4N+1- is not so great.

This reaction is carried out in water and/or an organic solvent such as acetonitrile, alcohol, or acetone, preferably acetonitrile or a mixed solvent of water and acetonitrile. Oxidation may be carried out by any method, but it is preferable to introduce oxygen into the reaction form in a gaseous form, such as oxygen or an oxygen-containing gas such as air, and the oxidizing agent is not present in the reaction system in excess of what is necessary. It's okay. There is no particular restriction on the reaction temperature, but it is usually carried out under mild conditions around room temperature. Although the reaction may be carried out for a long time, it is usually carried out for 1 minute to 2 hours or more (several days). The amount of (nBu)4W1- used is not particularly determined, but
It is preferred to use 0.73 to 3.7 moles of the corresponding quaternary salt. Light irradiation is carried out using a conventional light source for photoreaction, but irradiation with a high-pressure mercury lamp is preferred. The quaternary salt is used as a prom salt or an iodo salt, and is particularly preferably used as an iodo salt.

After the reaction mixture is treated in an aqueous sodium sulfite solution, the product can be isolated and purified by conventional methods. Furthermore, this reaction proceeds even in a weakly alkaline aqueous solution, and the desired product can be obtained in a similar high yield. As the weakly alkaline aqueous solution, a sodium bicarbonate aqueous solution is preferred. This reaction is difficult to proceed under acidic conditions. Next, some examples of Q-keto acids produced by the method of the present invention will be listed, but the Q-keto acids obtained by the method of the present invention are not limited to the following examples. Next, the present invention will be specifically described with reference to Examples.

Example 1 Synthesis of 2-oxo-n-dodecanoate 1 mmol of 1-ethoxycarbonylundecylviridinium iodide and 0.0 mmol of tetra-n-butylammonium iodide were placed in a Pyrex test tube 30 equipped with an injection tube. 73 mol
was dissolved in 20 ml of acetonitrile.

It was irradiated for 60 minutes with a 400W high-pressure mercury lamp while increasing oxygen gas from the jet. After irradiation, the reaction solution was added to 50% of a saturated aqueous solution of sodium sulfite, and then added to 30M of ether.
was added and shaken until the color of iodine disappeared, and then the ether layer was separated. The aqueous layer was further extracted twice with 30 parts of ether, and the ether solutions were combined and dried over sodium bran sulfate. After removing the solvent under reduced pressure, the liquid was separated by silica gel thin film chromatography (developing solvent: benzene), and 2-oxo-dodecanoate ethyl
Obtained with a yield of 3%. Elemental analysis (%) C, 4 days 260
Calculated value as 3 C: 69. Spot H: 10.81 Measured value C: 69.15 H: 10.63 IR (inhibition-1) 2910 (S), 2840 (S), 17
55(S), 1725(S), 1460(m), 125
5(S)NMR (CDC13) (6) 0.77-1.
03 (m, Zu), 1.10-1.67 (m, 1 group), 2
．． 83 (t, J = 7HZ), 4.35 (q, wave, J
■: 7 Hz), Example 2 In a Pyrex test tube 30M equipped with a synthetic injection tube for ethyl oxophenylethanate, 1 mmol of ethoxycarbonyl besodylpyridinium iodide and 0.73 wmol of tetra-n-butylammonium iodide were added.
was dissolved in 20M acetonitrile.

Irradiation was performed for 3 minutes using a 400W high-pressure mercury lamp while passing oxygen gas through the injection tube. After irradiation, the reaction solution was added to a saturated aqueous solution of sodium sulfite, then ether 30' was added, and the mixture was shaken until the color of iodine disappeared, and then the ether layer was separated. The aqueous layer was further extracted twice with ether (30%), and the ether solutions were combined and dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the residue was subjected to silica gel thin layer chromatography (developing medium: benzene) to obtain ethyl oxophenylethanate in a yield of 86%. Elemental analysis (%) Calculated value as C, mountain, o03 C: 67.40H: 5.66 Measured value C: 67.26H: 570 m (arc-1) 3050 (W), 2962 (m), 173
3(S), 1685(S), 1595(m), 1448
(m), 1320(S), 1300(S) NMR (CD
C13) (6) 1.17 (t, thin, J=7HZ), 4
．． 52 (q, 2 days, J=7HZ), 7.35-7.80
(m, spot), 8,00-8.13 (m, 2H) Example
3-7 The compounds shown in the following table were obtained in the same manner as described in Examples 1 and 2 above.

Example 8 Synthesis of ethyl oxophenylethanate In a Pyrex test tube (30 tubes) equipped with an injection tube, 1 mol of 1-methyl-2-(a-ethoxycarbonylbenzylthio)-pyridinium iodide and tetraiodide were added. -n
- 3.7 mol of butylammonium was taken and dissolved with 20 ml of acetonitrile.

Light was irradiated for 30 minutes with a 400W high-pressure mercury lamp while passing oxygen gas through the injection tube. After irradiation, the reaction solution was poured into a saturated aqueous solution of sodium sulfite, and 30% of methylene chloride was added thereto, followed by shaking until the color of iodine disappeared. After separating the methylene chloride layer, the aqueous layer was further extracted twice with methylene chloride (30 cm), and the methylene chloride solutions were combined and dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the residue was subjected to silica gel chromatography (developing solvent: benzene) to obtain ethyl oxophenylethanate in a yield of 85%. Example 9 Synthesis of 2-oxo-n-dodecanoate ethyl 1-methyl-2-(1-ethoxylcarbonyl-n-untesylthio)-pyridinium iodide was added in a Pyrex test tube (3'.) equipped with a jet tube. Tetra-n uride
- 3.7 mmol of butylammonium was taken and dissolved in 20 molar acetonitrile.

Six ships were irradiated with light using a 400W high-pressure mercury lamp while passing oxygen gas through the injection tube. After irradiation, the reaction solution was added to a saturated aqueous solution of sulfite, and 30 M of methylene chloride was further added, and the mixture was shaken until the color of iodine disappeared, and then the methylene chloride layer was separated. The aqueous layer was further extracted twice with 30M methylene chloride, and the methylene chloride solutions were combined and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was subjected to silica gel thin layer chromatography (developing solvent: benzene) to obtain ethyl 2-oxo n-dodecanoate in a yield of 58%. Examples 10 to 12 The compounds shown in the following table were obtained from the corresponding thiopyridinium salts in the same manner as described in Examples 8 and 9 above.

Claims (1)

[Claims] 1 General formula (1) ▲ Numerical formulas, chemical formulas, tables, etc. are included. It is a group heterocycle or an alkoxycarbonyl alkyl group, and A^+ has ▲ a mathematical formula, a chemical formula, a table, etc. ▼ or ▲ a mathematical formula, a chemical formula, a table, etc. ▼ (R_3, R_4 are hydrogen atoms or alkyl groups, R_5
represents an alkyl group), X^- represents a halogen ion], (n-Bu)_4N^+
General formula (2)▲ characterized by being oxidized with oxygen under light irradiation in the coexistence of I^- (Bu represents a butyl group)
There are mathematical formulas, chemical formulas, tables, etc. ▼ (R_1 in formula (2)
, R_2 represents the same meaning as described above).