JPS6321664B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to novel substituted acetaldehydes. More specifically, the invention relates to the general formula (wherein R ¹ is hydrogen or an alkyl group having 1 to 4 carbon atoms) or an enol isomer thereof. general formula (R ¹ is the same as above) α-(2-
Pyridyl)arylacetonitrile is used for various physiologically active substances (e.g. disopyramide, an antiarrhythmia drug).
It is known as a raw material for manufacturing. Conventionally, a method using a reaction between benzyl cyanide and 2-chloropyridine has been known to obtain the above-mentioned nitriles, but the raw materials cannot be prepared at low cost, and the yield of this reaction is not good, so it is not necessarily an excellent method. I couldn't call it a method. By using α-(2-pyridyl)arylacetaldehyde of the above formula (or its enol isomer) created by the present inventors, not only can such nitriles be produced with good yield, but also the aldehyde itself can be produced at low cost. Since it can be synthesized, it has become possible to economically produce the nitrile. The present invention therefore provides new substituted aldehydes (or enol isomers thereof) useful for producing said nitriles.
is intended to provide. In the above formula, R ¹ is hydrogen or an alkyl group having 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl,
When it is tert-butyl and R ¹ is an alkyl group,
in position 2-, 3- or 4-. Specific examples of α-(2-pyridyl)arylacetaldehyde represented by the above formula include:

【formula】

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[Formula] etc. can be exemplified. To produce these α-(2-pyridyl)arylacetaldehydes (or their enol isomers), the general formula 2- represented by (in the formula, R ¹ is the same as above)
It can be obtained by reacting benzylpyridines with a formic acid ester, such as methyl formate or ethyl formate, in the presence of a base such as sodium hydride, sodium ethoxy, potassium tert-butoxy, etc., and then neutralizing it. In this reaction,
It is preferable to use about 1 to 5 moles of formic acid ester and about 1 to 3 moles of base per mole of 2-benzylpyridine, and the reaction temperature is preferably in the range of 10 to 120°C. Further, the reaction can be carried out more advantageously by using a reaction solvent such as dimethyl sulfoxide, dimethylformamide, or tetrahydrofuran in an amount of 5 to 30 parts by weight per 1 part by weight of the 2-benzylpyridine. Furthermore, the reaction system was heated under a carbon monoxide atmosphere.
In particular, good results can also be obtained by maintaining the partial pressure under conditions of 1 to 100 Kg/cm ² . After the reaction is completed, unreacted raw materials, solvent, etc. are separated, and in order to isolate the target α-(2-pyridyl)arylacetaldehyde (or its enol isomer), after neutralization with protonic acid, Conventional separation means such as extraction, distillation, and recrystallization may be appropriately employed. The α-(2-pyridyl)arylacetaldehyde thus obtained usually has the general formula It has an enol structure represented by , and is a yellow liquid or crystal. The α-(2-pyridyl)arylacetaldehyde (or its enol isomer) of the present invention can be converted to the corresponding nitrile by reacting with a neutralizing agent such as hydroxylamine sulfate or hydrochloride and sodium carbonate to form the oxime. A method may be adopted in which the oxime is then dehydrated in the presence of a base. As described above, α-(2-pyridyl)arylacetaldehyde (or its enol isomer) of the present invention is easy to produce, and α-(2-
It is an excellent reaction intermediate because it can be converted to pyridylacetonitrile in high yield. Next, examples will be shown. Example 1 2.0 g (18 mmol) of tert-butoxypotassium and 10 ml of dimethyl sulfoxide were placed in a flask with an internal volume of 50 ml, and the inside of the flask was purged with nitrogen. Add to this 1.7 g (10 mmol) of 2-benzylpyridine.
was added at 40°C. Then, at 40℃ while stirring, 1.5
g (20 mmol) of ethyl formate was added dropwise over 2 hours using a microfeeder. The resulting reaction mixture was poured into 100 ml of water, neutralized with dilute sulfuric acid, and then extracted with toluene. The toluene layer was dried with sodium sulfate and distilled under reduced pressure to a boiling point of 116°C (0.35°C).
1.9 g of a yellow liquid was obtained. When this liquid was left to stand, it turned into yellow crystals with a melting point of 32-34°C, and the following analytical values showed that it was α-(2-pyridyl)phenylacetaldehyde (yield: 96%). Furthermore, it was found from the IR spectrum and NMR spectrum that α-(2-pyridyl)phenylacetaldehyde has an enol structure. Elemental analysis value C: 79.20%, H: 5.59%, O: 8.15%, N: 7.06% Calculated value as C ₁₃ H ₁₁ ON C: 79.16%, H: 5.62%, O: 8.11%, N: 7.10% Mass spectrum m/e: 197 (M ⁺ ), 196, 168 IR spectrum (neat, cm ^-1 ) 3040 (W), 3000 (W), 1614 (S), 1588 (S),
1490 (m), 1467 (S), 1448 (m), 1435 (m),
1222 (S), 1135 (S), 942 (m), 783 (m),
764 (m), 738 (m), 700 (S) NMR spectrum (100 NHz, in CDCl ₃ , TMS standard) δ 6.94-7.62 (9H, m), 8.14 (1H, m), 15.5
(1H, broad, OH) Reference example α-(2-pyridyl) in a flask with an internal volume of 200ml
Phenylacetaldehyde 24.0g (0.122mol),
Ethanol 40ml, hydroxylamine hydrochloride 10.0
g (0.144 mol) and 20 ml of water, then 30
Add 28.6g of % sodium carbonate aqueous solution and heat to 15% at 120℃.
Stir for a minute. After cooling, the reaction mixture was extracted with ether, and the ether layer was dried over sodium sulfate and then concentrated under reduced pressure to obtain 25.9 g of α-(2-pyridyl)phenylacetaldoxime (yield: 100%). α-(2-pyridyl) in a flask with an internal volume of 100ml
Phenylacetaldoxime 6.4g (0.03mol),
1.2 g (0.03 mol) of sodium hydroxide and 50 ml of dimethyl sulfoxide were added, and the mixture was stirred at 120°C for 30 minutes. After cooling, the reaction mixture was neutralized with acetic acid, and α-(2-pyridyl)phenylacetonitrile was analyzed and quantified by gas chromatography, and the yield was 88%.

Claims (1)

[Claims] 1. General formula α-(2-pyridyl)arylacetaldehyde or its enol isomer represented by (wherein R ¹ is hydrogen or an alkyl group having 1 to 4 carbon atoms).