JPS6345384B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to novel substituted acetaldoximes. More specifically, the present invention is based on the following formula (wherein, R is hydrogen or an alkyl group having 1 to 4 carbon atoms)
pyridyl)acetaldoxime. general formula α-aryl-α-(2-pyridyl)acetonitrile represented by the formula (wherein R is the same as above) is a useful compound that is a raw material for manufacturing pharmaceuticals such as disopyramide, and conventionally used with benzyl anides and 2-pyridyl). A method for producing it by reaction with halopyridine was known. However, this reaction has the drawbacks of poor yield and the need to use expensive 2-halopyridine. α-aryl-α-(2-pyridyl) of the present invention
Acetaldoxime is a useful compound that can be converted into the above-mentioned nitriles in high yield by dehydration, and the provision of this compound has made it possible to avoid the above-mentioned drawbacks of conventional methods. α-aryl-α-(2-pyridyl) of the present invention
A specific example of acetaldoxime is

【formula】

【formula】

【formula】

【formula】

【formula】

[Formula] etc. can be exemplified. α-aryl-α-(2-pyridyl) of the present invention
To produce acetaldoxime, use the following formula (In the formula, R is the same as above) α-aryl-α-(2-pyridyl)acetaldehyde and hydroxyamine may be reacted. In addition, α-aryl-α-(2-pyridyl) shown in the above formula
Acetaldehyde is also a new compound and can be obtained by reacting the corresponding benzylpyridines with formic acid esters in the presence of a strong basic catalyst. Details of such reactions are given in the co-dated application. 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, 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, dimethylformamide, dimethylamide, and hexamethylphosphorus. Examples of the solvent include aprotic polar solvents such as amide and mixtures thereof with water, alcohols such as methanol, 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 between 10 and
A temperature of 150°C, especially in the range from 25 to 120°C, is advantageous. After the reaction is completed, the target substituted acetaldoxime 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 solvent 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 ); (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)or(k);δ.8.57(doublet) (f)and(l);δ.9.7(broad) Reference example α-phenyl-α-(2-pyridyl)acetaldoxime 6.4g (0.03 mol), NaOH 1.2g
(0.03 mol), and 100 ml of dimethyl sulfoxide
The mixture was heated and stirred at 120°C for 300 minutes to react. The reaction mixture was cooled, neutralized with acetic acid, and then analyzed using a gas chromatograph (Dia Solid ZS,
2m), the yield of nitrile compound was 93
It was %.

Claims (1)

[Claims] 1. General formula (wherein, R is hydrogen or an alkyl group having 1 to 4 carbon atoms)
pyridyl) acetaldoxime.