Substituted Quinolinones. Part 19. New and Unexpected Results from Oxidation of 3-Acetyl-1-Alkyl- 4-Hydroxyquinolin-2(1H)-Ones Using Selenium Dioxide

Abstract

Oxidation of 3-acetyl-1-alkyl-4-hydroxyquinolin-2(1H)-ones using selenium dioxide under Riley conditions was described. The oxidation reaction produced a mixture of 2 unexpected α-keto acid and its dehydrated dimer derivatives. The oxidation reaction was studied under different reaction conditions in order to maximize the yields and optimize reaction conditions. Also, 1-alkyl-4-hydroxy-3-(2-nitroacetyl)quinolin-2(1H)-one and/or 3-acetyl-1-alkyl-4-diflouro-boryloxyquinolin-2(1H)-one derivatives were subjected to the same oxidation reaction giving rise improved reaction yields and selectivity in case of the boron-complex. Alkaline degradation of the dehydrated dimers led to formation of the 4-hydroxy-2-oxoquinoline-3-carboxylic acids while under the same conditions the α-keto acids underwent deoxalylation.

[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the following free supplemental files: Additional figures].     

Preparation of 2,4,5-trisubstituted pyrazolo[4,3-c]quinolin-3-ones

The preparation of pyrazolo[4,3-c]quinolinones is reported starting from 2-substituted-5-(2-fluorophenyl)-3-oxo-2,4-dihydro-3H-pyrazol-3-ones. A one-pot protocol, in which condensation with an orthoamide followed by substitution with a primary amine and subsequent S_NAr-cyclization to provide rapid access to 4- and 5-substituted pyrazolo[4,3-c]quinolinones was developed.     

DABCO-促进新型呋喃并[3,2-c]喹啉酮类化合物的合成

在1,4-二氮杂二环[2.2.2]辛烷(DABCO)促进下,以水为反应介质,通过3-溴乙酰基-4-羟基-1-甲基-2-喹啉酮与芳香醛的亲核取代、分子内环化及消除的串联反应,合成了9个新型的呋喃并[3,2-c]喹啉酮类化合物,其结构经~1H NMR,~(13)C NMR,IR,MS(ESI)和元素分析表征。     

Synthesis,Characterization, and Antimicrobial Evaluation of Some Novel 4-Hydroxyquinolin-2(1H)-ones

Vilsmeier–Haack formylation of 3-acetyl-1-methyl-4-hydroxyquinolin-2(1H)-one (2) produced the novel 6-methyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde (3). Reactions of carboxaldehyde 3 with a diversity of nucleophilic reagents were studied and a variety of products were obtained via ring-opening, ring-closing (RORC) sequence. Also, some novel heteroannulated pyrano[3,2-c]quinolines were prepared. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

~1H NMR确证6-氟-5(或7)-氯-3-苯基-4-(1H)-喹啉酮衍生物的结构

作者合成了６氟３（取代）苯基４（１Ｈ）喹啉酮的５氯衍生物与７氯衍生物，二者极性差异小，难于分离，以混合物形式存在．所合成的化合物均未见文献报道，本文通过１ＨＮＭＲ上的化学位移、积分面积以及偶合常数确证了混合物中两组份的结构．     

喹啉酮衍生物的合成及其心血管活性

异黄酮化合物具有心血管活性[1],雌激素活性[2]及抗骨质疏松[3]活性等。3 苯基 4(1Ｈ)喹啉酮衍生物是异黄酮化合物的等电子体,文献报道它具有与异黄酮化合物相似的心血管活性[4]和抗肿瘤[5]活性。结构中具有氟原子的化合物大多能改善脂溶性,增强生理活性,且能选择性作用于脑细胞及脑血管;喹诺酮类抗菌药中具有优良抗菌活性的化合物几乎都含有氟原子。我们对含氟的3 苯基 4(1Ｈ)喹啉酮类化合物进行了研究。以氟氯苯胺为原料,合成了其7 氯衍生物(化合物Ａ1～Ａ4),及5 氯衍生物(化合物Ｂ1～Ｂ4),其中7 氯衍生物为主产物,合成路线如下:化合…     

6-羟基-3,4-二氢-2(1H)喹啉酮合成新方法

提出了一种以苯胺和3-氯丙酰氯为原料，经环合、硝化、还原、重氮化水解合成目标产物6-羟基-3，4二氢-2(1H)喹琳酮的新方法。此法合成的目标产物产率高，总产率达67％以上。单步产率均在86．5—99．6％之间，反应条件温和。各步产品经MS，1HNMR进行定性及结构表征。     

New alkaloids from <Emphasis Type="Italic">Casimiroa edulis</Emphasis> fruits and their pharmacological activity

The extract of Casimiroa edulis was investigated for antihypertensive activity. The ethanol and total alkaloids (in chloroform) extracts were found to have antihypertensive properties at doses of 500 and 200 mg/kg, respectively. Four quinolinone alkaloids were isolated and identified as: 2-(2′-hydroxy-4′-methoxyphenyl)-5,8-dimethoxy-3-propyl-1H-quinolin-4-one (1), 5,8-dimethoxy-2-(3′-methoxyphenyl)-3-propyl-1H-quinolin-4-one (2), 5,8-dimethoxy-2-(3′,4′-dimethoxyphenyl)-3-propyl-1H-quinolin-4-one (3), and 5,6-dimethoxy-2-(2′,5′,6′-trimethoxyphenyl)-1H-quinolin-4-one (4). Interestingly, compounds 1, 2, and 3 were found to be new alkaloids. The four isolated alkaloids showed antihypertensive activity at doses of 50, 100, 200, and 300 mg/kg, respectively. Published in Khimiya Prirodnykh Soedinenii, No. 5, pp. 473–476, September–October, 2007.     

色满-4-酮并[2,3-b]喹啉酮衍生物的合成

以丙酮和适当的芳香醛以及丙二酸二乙酯为原料，合成出未见报道的5-芳基- 1，3-环已二酮作为合成块。利用Friedlaender合成法与2-氨基-3-甲酰基色满-4- 酮缩合，首次完成色满-4-酮并[2,3-b]喹啉酮新四环系化合物的合成。所合成的化 合物均经~1H NMR,~(13)C NMR，IR光谱和元素分析予以证实。化合物2a的结构也从 色谱-质谱联机分析的质谱数据得到进一步确认。化合物的药理学离体实验表明， 化合物2a具有较强的抑制肿瘤细胞生长的活性。     

5-氨基-5,6,7,8-四氢-2(1H)-喹啉酮的简便合成

改进了合成5-氨基-5,6,7,8-四氢-2(1H)喹啉酮(5)的方法。以环己二酮为原料,通过亚胺化,Michael反应-环化反应,成肟反应和碱性条件下镍铝合金催化还原共四步反应合成了5,总收率19.6%,其结构经1HNMR,IR和MS确证。