Various β-ketoamides were conveniently prepared by direct aminolysis of acyl Meldrum's acids. Aminolysis with substituted anilines underwent smoothly regardless of different substituent effects. Noteworthy was weakly nucleophilic amines such as 2-aminopyridine, and 2-nitroaniline afforded the corresponding β-ketoamide in excellent yields. In the same manner aliphatic primary and secondary amines underwent aminolysis effectively, even sterically congested diisopropylamine gave the amide without any difficulties. Subsequently β-ketoamides were transformed into ketene dithioacetal α-anilides in high yields by using carbon disulfide and alkyl halide in the presence of potassium carbonate. Thermal cyclization reaction took place smoothly either by heating ketene dithioacetals in an inert solvent like odichlorobenzene at reflux temperature for 2-4 hr or by direct thermolysis at the temperature slightly above its melting point giving off alkyl mercaptan. After cooling the reaction mixture, crystalline solid was filtered to give 3-acyl-4-alkylthio-2-(1H)-quinolinones in respectable yields.
In the same manner β-keto amides from amino heterocycles such as aminopyridines and aminopyrimidine were subjected to the condition to make the corresponding ketene dithioacetals. However it was not possible to isolate ketene dithioacetals of aminopyridines since under the condition cyclization took place simultaneously to give the cyclized products. But β-keto amide from 4.6-dimethyl-2-aminopyrimidine gave the corresponding ketene dithioacetal which was isolated and further cyclized into 3-acetyl-6,8-dimethyl-4-methylthio-2H-pyrimido[1,2-a]pyrimidin-2-one.
In an effort to expand its scope, we applied this reaction to the formation of 2(1H)-pyridone skeleton. Thus β-keto enamides were prepared by adding appropriate β-ketoester enolate to the substituted trans vinyl isocyanate followed by heating the adduct in DMSO to eliminate carboalkoxy group. Subsequent formation of ketene dithioacetal enamide was carried out as usual to give the 2-pyridones in decent yields.
2-Acetyl(ethoxycarbonyl)methylene-1,3-dithietane and -dithiane were condensed with various aldehyedes or ketones to afford high yields of the corresponding substituted 2-(1-carboxy-2-oxo-3-butenylidene)-1,3-dithietanes and -dithianes, which upon heating decaboxylated smoothly to give the alkenoyl-and cinnamoylketene dithioacetals in high yield.
아실멜드럼산과 아민과의 반응에 의해 얻어진 β-케토카복사미드 중 β-케토아닐리드로 부터 케텐디티오 아세탈 α-아닐리드를 만들어 열고리화 반응을 시킨 결과 3-아실-4-알킬티오-2-퀴놀린온(103)을 좋은 수율로 합성하였으며, 아민이 포함된 헤테로 사이클 아민과 디케텐 반응에 의해서 얻어진 아세토아세트 헤테로 사이클 아미드를 이황화 탄소 및 요오드메탄과 반응시킨 결과 2-아미노피리딘인 경우에는 케텐디티오 아세탈을 거치지 않고 직접 2H-피리도[1,2-a]피리미딘-2-온(120)이 얻어졌으며, 2-아미노 피리미딘인 경우에는 케텐디티오 아세탈을 거쳐 열고리화 반응에 의하여 2H-피리미도[1,2-a]피리미딘-2-온이 얻어졌다. 한편 비닐 이소시아네이트로 부터 α-에톡시카보닐 -β-케토엔아미드를 디알콕시카보닐화하여 β-케토엔아미드를 얻어 이황화 탄소와 요오드 메탄과의 반응에 의해 얻어진 케텐디티오 아세탈 α-엔아미드를 열고리화 반응시켜 3-아세틸-4-메틸티오-2-피리돌(121)을 얻었다.
◁그림 삽입▷(원문을 참조하세요)
위와 같이 얻어진 3-아실-4-아킬티오-2-퀴놀린온은 히드라진과의 반응에 의하여 4H-피라졸로 [4,3-c]퀴놀린-4-온이 얻어지며 산화에 의해서는 3-아실-4-알킬설폭시-2-퀴놀린온이 얻어지는데 이것을 가수분해하면 3-아실-4-히드록시-2-퀴놀린온과 3-아실-4-알킬티오-2-퀴놀린온이 동시에 얻어진다. 또한3-아실-4-메틸티오-2-퀴놀린온은 상전이 촉매 중에서 요오드메탄또는 벤질브로마이드로 알킬화 시키면 설포니윰염이 생기며 이것을 가열하면 3-아실-2-알콕시-4-메틸티오퀴놀린이 되며 벤질설포니움염은 염기 존재하에서 반응시키면 3-아세틸과 분자내 반응을 하며 티오페놀이나 벤질아민으로 친핵성반응을 시키면 벤질페닐설파이드와 디벤질 아민이 얻어진다.
한편 β-케토에스테르로 부터 얻어진 2-아세틸 (에톡시카보닐) 메틸렌이 -1,3-디티에탄과 디티안을 알데히드 또는 케톤과 염기중에서 반응시키면 -2-(1-카복시-2-옥소-3-부테닐리덴)-1.3-디티에탄과 디티안이 얻어지며 이것을 디카복실화 시키면 알케노일 또는 신남오일 케텐디티오 아세탈이 좋은 수율로 얻어진다.
