JPS6321665B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel process for preparing substituted acetaldoximes. More specifically, the present invention provides the general formula (wherein R ¹ and R ² represent hydrogen, a lower alkyl group, a lower alkoxyl group, or a halogen) and hydroxylamine are reacted. The present invention relates to a method for producing a substituted acetaldoxime represented by the formula (wherein R ¹ and R ² are the same as above). general formula α-Arylpyridine acetonitrile represented by the formula (wherein R ¹ and R ² are the same as above) is a useful compound that serves as a raw material for manufacturing pharmaceuticals such as disopyramide. A method of producing it by a similar reaction was known. However, this reaction has the disadvantage of poor yield, as well as the fact that the benzyl cyanides used as raw materials are synthesized using toxic NaCN, and the halogen cypyridines are expensive. By using the substituted acetaldoxime of the above formula obtained by the present invention, it can be easily converted into the α-arylpyridine acetonitrile of the above formula in high yield, so that the above-described drawbacks and difficulties of conventional methods can be avoided. . The substituted acetaldehyde of the above formula used as a raw material in the present invention is a new compound and can be obtained by reacting the corresponding benzylpyridine and formic acid ester in the presence of a strong base catalyst. Details of such reactions are given in patent applications dated the same date as this application. In the above formula of substituted acetaldehyde, R ¹ and R ² are
Hydrogen; lower alkyl groups, such as methyl, ethyl,
n-propyl, iso-propyl, n-butyl, sec
-butyl, tert-butyl, etc.; lower alkoxyl groups, such as methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, etc.; halogens, such as fluorine, chlorine, bromine, iodine, etc. It is chosen. More specifically,

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[Formula] etc. can be exemplified. When reacting the substituted acetaldehyde with hydroxylamine, in consideration of safety, hydroxylamine is supplied to the reaction system in the form of sulfate or hydrochloride, and a base is also supplied to the reaction system. It is preferable to carry out the reaction while liberating. Examples of the base used for this purpose include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium acetate, and triethylamine. In order to carry out the reaction smoothly, it is preferable to use a solvent that dissolves the substituted acetaldehyde as the reaction medium, such as aromatic hydrocarbons such as benzene, toluene, and xylene, dimethyl sulfoxide, dimethyl formamide, dimethyl acetamide, hexamethyl phosphor aprotic polar solvents such as Ruamide and their mixtures with water, methanol,
Examples include alcohols such as ethanol and isopropanol, and mixtures thereof with water. The amount of hydroxylamine used is preferably 0.5 to 5.0 mol, particularly 1.0 to 2.0 mol, per 1 mol of substituted acetaldehyde.
Also, when using a salt of hydroxylamine, the amount of base used may be equal to or in excess to liberate the hydroxylamine. When using a reaction solvent, it is effective to use about 2.0 to 10.0 parts by weight per 1 part by weight of substituted acetaldehyde. The reaction temperature is 10 or
A temperature of 150°C, especially in the range from 25 to 120°C, is advantageous. After the reaction is completed, the target substituted acetaldehyde oxime can be isolated by a conventional method. The substituted acetaldoxime obtained in the present invention is a useful intermediate that can be easily converted into the corresponding nitrile by the action of a dehydrating agent. Next, an example will be explained. Example 1 α-phenyl-α-(2-pyridyl)acetaldehyde 24.0 g (0.12 mol), ethanol 40 ml,
Hydroxylamine hydrochloride 10.0g (0.14mol),
29.7g of 30% sodium carbonate aqueous solution (as sodium carbonate)
0.28 mol) and stirred at 120°C for 15 minutes. The reaction mixture was extracted with ether and dried according to a conventional method.
When concentrated, the crude crystals of the desired oxime form 25.9
g (yield 100%). This was recrystallized from a toluene-hexane mixed medium to obtain a pure oxime with a mp of 116-118°C. The analysis results are shown below. Elemental analysis Calculated value for C ₁₃ H ₁₂ N ₂ O, C, 73.56; H, 5.70; N, 13.20 Measured value for C ₁₃ H ₁₂ N ₂ O, C, 73.84; H, 5.61; N, 13.05 Infrared spectrum ( KBr Disc) 3200 (cm ^-1 ) (νOH), 3040 & 2860 (νC-H) 1590 (νC=N), 1470, 1430, 955, 745, 700 Nuclear magnetic resonance spectrum (CDCl ₃ );

[Formula] and

Mixture of [formula] (a) or(g); δ.5.08or5.80 (doublet, J=7Hz) (b) and(h); δ.7.30 (multiplet) (c) or(i); δ. 7.46orδ.8.02 (doublet, J=7Hz) (d) and(j);δ.7.2～7.6(multiplet) (e) and(k);δ.8.57(doublet) (f) and(l);δ .9.7 (Broad) Example 2 α-phenyl-α-(2-pyridyl)acetaldehyde 5.9 g (0.03 mol), hydroxylamine hydrochloride 2.7 g (0.04 mol), triethylamine 10
ml and 40 ml of toluene was stirred at 100°C for 40 minutes. 40 ml of water was added to the reaction mixture, extracted with 100 ml of ether, and the organic layer was post-treated in the same manner as in Example 1 to obtain 6.4 g of the desired oxime (yield: 100%). Example 3 α-phenyl-α-(2-pyridyl)acetaldehyde 5.9 (0.03 mol), hydroxylamine hydrochloride 2.8 g (0.04 mol), sodium acetate 4.3 g
(0.05 mol), and 40 ml of DMSO at 100°C.
The mixture was stirred for 40 minutes. Add 40ml of water to the reaction mixture,
After extraction and separation with 100 ml of ether, the organic layer was prepared in Example 1.
Treat in the same manner as to obtain the desired oxime form.
Obtained in a yield of 5.9 g (92% yield). Example 4 α-phenyl-α-(2-pyridyl)acetaldehyde 6.1 g (0.03 mol), hydroxylamine sulfate 3.3 g (0.02 mol), potassium hydroxide 2.3 g
(0.04 mol), 30 ml of DMSO, and 50 ml of water was stirred at room temperature for 1.0 hr. The reaction mixture was extracted with toluene and the organic layer was dried over anhydrous sodium sulfate and concentrated to yield 6.2g of the desired oxime.
The yield was 97%. Example 5 7.4 g of a 30% aqueous sodium carbonate solution was added to a solution consisting of 5.9 g (0.03 mol) of α-phenyl-α-(2-pyridyl)acetaldehyde, 3.3 g (0.02 mol) of hydroxylamine sulfate, 10 ml of ethanol, and 5 ml of water. (0.07 mol as sodium carbonate) was added, and the mixture was heated and stirred at 120°C for 30 minutes. The reaction mixture was treated according to Example 1 to give the corresponding oxime in 93% yield.

Claims (1)

[Claims] 1. General formula (In the formula, R ¹ and R ² are hydrogen, lower alkyl group,
A general formula characterized by reacting a substituted acetaldehyde represented by a lower alkoxyl group or a halogen) with hydroxylamine. (R ¹ and R ² are the same as above) A method for producing a substituted acetaldoxime. 2. The production method according to claim 1, wherein the reaction is carried out in the presence of a solvent.