噻唑啉-2-硫酮衍生物的合成与生物活性

根据活性亚结构拼接原理,将3-芳基-4-氨基-5-乙氧羰基(氰基)-3H-噻唑啉-2-硫酮与酰氯反应得到目标化合物3-芳基-4-取代苯氧乙酰氨基-5-乙氧羰基(氰基)-3H-噻唑啉-2-硫酮.再以3-苯基-4-氨基-5-乙氧羰基-3H-噻唑啉-2-硫酮为合成原料,经过Aza-Wittig反应得到目标化合物5-芳氧基-3,6-二芳基-2-硫代噻唑并[4,5-d]嘧啶-7-酮.通过IR,1H NMR,EI-MS,元素分析等方法对所合成的化合物进行了结构表征.代表化合物5-对氯苯氧基-3,6-二苯基-2-硫代-2,3-二氢噻唑并[4,5-d]嘧啶-7(6H)-酮(C1)经单晶X衍射证实了结构.除草活性测试结果表明:部分噻唑啉-2-酮类衍生物对稗草和油菜都表现出了较好的抑制活性.     

新型5-芳甲酰胺基-6-芳胺基-吡唑并[3,4-d] 嘧啶-4-酮衍生物的合成及其除草活性

以吡唑膦亚胺、芳基异氰酸酯和芳基甲酰肼为原料，通过串联氮杂Wittig反应关环合成了12种新型的5-芳甲酰胺基-6-芳胺基-吡唑并[3,4-d]嘧啶-4-酮衍生物(3a~3l)，其结构经¹H NMR, ¹³C NMR， IR和HR-MS(ESI)表征。对单双子叶除草活性的初步测试结果发现：部分化合物具有优异的除草活性，特别是浓度为100 mg·L^-1时，5-(4-氟苯甲酰胺基)-6-(4-氯苯胺基)-3-甲硫基-1-苯基-1H-吡唑[3,4-d]-嘧啶-4(5H)-酮3i和5-(4-吡啶苯甲酰胺基)-6-(4-氯苯胺基)-3-甲硫基-1-苯基-1H-吡唑[3,4-d]-嘧啶-4 (5H)-酮3k对油菜和稗草的茎和根的抑制率高达100%。     

新型噻吩并嘧啶酮类衍生物的合成及其抑菌活性

以1,2,4-三氮唑为起始原料,经取代、Gewald反应、Wittig反应和成环反应合成了7个新型的含氟噻吩并嘧啶酮类衍生物——2-二烷氨基-3-对氟苯基-5-甲基-6-(1H-1,2,4-三唑-1-基)-噻吩并[2,3-d]嘧啶-4(3H)-酮(6a~6g),其结构经1H NMR,MS和元素分析表征。抑菌活性测试结果表明:6对棉花枯萎菌、水稻纹枯菌、黄瓜灰霉菌、小麦赤霉菌、苹果轮纹及棉花炭疽具有较好的抑制作用,其中2-二异丁氨基-3-对氟苯基-5-甲基-6-(1H-1,2,4-三唑-1-基)-噻吩并[2,3-d]嘧啶-4(3H)-酮(6f)的抑菌活性最好,在用药量为5×10-5g·L-1时,对棉花枯萎菌的抑制率为85%。     

新型含吲唑环嘧啶衍生物的合成

以6-硝基-1H-吲唑为原料,经氮原子甲基化、催化氢化还原、亲核取代以及烷基化反应制得关键中间体N(2′-氯嘧啶-4′-基)-N,1-二甲基-1H-吲唑-6-胺(5);5与芳香胺进行亲核取代反应合成了一系列新型取代氨基嘧啶衍生物——N-(2′-取代氨基嘧啶-4′-基)-N,1-二甲基-1H-吲唑-6-胺,其结构经1H NMR和MS表征.     

苯桥连的双[噻唑并[4,5-d]嘧啶-7(6H)-酮]衍生物的合成

在乙醇钠的催化下,4-[(三苯基膦叶立德)氨基]-2,3-二氢-3-苯基-2-硫代噻唑-5-羧酸乙酯(膦亚胺1)与芳香基二异氰酸酯和亲核试剂的双氮杂Wittig反应制得苯桥连的双[噻唑并[4,5-d]嘧啶-7(6H)-酮]衍生物,产率为56%～92%.产物结构经IR,1H NMR,MS和元素分析确证.     

3-(2-氟-4-氯-5-取代基苯基)-7-甲基-3H-吡唑并[3,4-d][1,2,3]三嗪- 4(7H)-酮化合物的合成及其对原卟啉原氧化酶的抑制活性

为了发现新型的原卟啉原氧化酶抑制剂, 根据生物合理设计方法, 设计并合成了一系列的结构新颖的3H-吡唑并[3,4-d][1,2,3]三嗪-4-酮衍生物. 利用不同取代的5-氨基-吡唑-4-甲酰氯与取代苯胺反应制得的5-氨基-N-苯基-1H-吡 唑-4-甲酰胺衍生物, 经进一步重氮化得到目标化合物, 并对化合物3f进行衍生化. 所得目标化合物的结构均经1H NMR, IR和元素分析确证. 生物活性测定结果表明, 部分化合物对原卟啉原氧化酶有较高的抑制活性, 讨论了其结构与活性的关系.     

多聚磷酸存在下取代6-苄硫基嘧啶与羧酸的环合反应研究

以多聚磷酸(PPA)为催化剂, 对取代6-苄硫基嘧啶与羧酸的反应进行了研究. 当羧酸为脂肪酸时, 在60-80 ℃下反应, 可选择性地得到6-苄硫基嘌呤衍生物; 改用芳香酸时, 则得到硫上的苄基被脱除的6-巯基嘌呤和嘧啶并[5,4-d]噻唑; 如果将嘧啶4-位上伯胺取代基变成仲胺取代基, 只得到嘧啶并[5,4-d]噻唑. 通过双途径反应机理对上述现象进行了解释.     

新型氨基功能化碱性离子液体1-(2-氨基乙基)-3-甲基咪唑咪唑盐催化四类取代2-氨基-4H-色烯衍生物的合成

设计合成了阴阳离子均具有碱性位点的新型氨基功能化碱性离子液体1-(2-氨基乙基)-3-甲基咪唑咪唑盐([2-aemim]im,3),经ESIMS和1H NMR确定了结构.[2-aemim]im的碱性与氨基功能化的阳离子([2-amim]+)有关,但主要取决于咪唑阴离子(im-).TG-DSC分析显示[2-aemim]im具有高的热稳定性.将[2-aemim]im用于催化水相介质中芳香醛、丙二腈和酚的三组分一锅法反应制备2-氨基-4H-色烯衍生物,阴阳离子之间表现出协同促进催化作用.该催化剂具有高效和底物作用范围广的特点,应用不同的酚类及类似物,如1-萘酚、2-萘酚、间苯二酚和环己二酮,以高产率得到了相应的不同官能团取代的2-氨基-4H-苯并[h]色烯(4a～4e),2-氨基-4H-苯并[f]色烯(5a～se),2-氨基-4H-色烯(6a～6e)和2-氨基-4H-四氢色烯(7a～7e)四类2-氨基-4H-色烯衍生物.离子液体至少可以循环使用5次,催化活性无显著降低.     

2-二烷氨基-3-苯基-5-甲基-6-(1H-1,2,4-三唑-1-基)-噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物的合成及其杀菌活性

用烯基膦亚胺与苯基异氰酸酯、仲胺的串联aza-Wittig反应合成了8个新的2-二烷氨基-3-苯基-5-甲基-6-(1H-1,2,4-三唑-1-基)-噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物(6a～6h),其结构经1H NMR, MS和元素分析表征.初步生物活性测试结果表明,部分6表现出一定的抑菌活性,其中6f在浓度为5×10-5g·L-1时,对棉花炭疽菌的抑制率达到87%.     

新型5,5'-双[对-(4-氨基苯氧基)苯氧基]联嘧啶的合成

2-氯-5-溴嘧啶通过碘代,Ullmann,Williamson和还原反应,合成了新型5,5'-双[对-(4-氨基苯氧基)苯氧基]联嘧啶,其结构经1H NMR,IR和元素分析表征.     

Synthesis of 2-substituted-5-halo-2,3-dihydro-4(H)-pyrimidin-4-ones and their derivatization utilizing the Sonogashira coupling reaction in the enantioselective synthesis of alpha-substituted beta-amino acids

A convenient, one-pot procedure for the synthesis of 1-benzoyl-2(S)-substituted-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones by tandem decarboxylation/beta-iodination of the corresponding 6-carboxy-perhydropyrimidin-4-ones was developed. In addition, several 1-benzoyl-2(S)-substituted-5-bromo-2,3-dihydro-4(H)-pyrimidin-4-ones were readily prepared by bromination of 1-benzoyl-2(S)-substituted-2,3-dihydro-4(H)-pyrimidin-4-ones. Subsequently, Sonogashira coupling of the halogenated heterocyclic enones with various terminal alkynes produced 1-benzoyl-2(S)-isopropyl-5-alkynyl-2,3-dihydro-4(H)-pyrimidin-4-ones in good yields. Hydrogenation of the unsaturated C-C moieties in the Sonogashira products followed by acid hydrolysis afforded highly enantioenriched alpha-substituted beta-amino acids.     

A general approach for the synthesis of 5-substituted-4-amino-pyrrolidin-2-ones and 5-substituted-4-amino-3-pyrrolin-2-ones

Short stereoselective syntheses of both 5-substituted-4-amino-pyrrolidin-2-ones and 5-substituted-4-amino-3-pyrrolin-2-ones from natural α-amino acids are described.     

Diastereoselective synthesis of alpha-methyl and alpha-hydroxy-beta-amino acids via 4-substituted-1,3-oxazinan-6-ones

1,3-oxazinan-6-ones have been utilized in a series of enolate reactions to produce 5-hydroxy and 5-alkyl-4-substituted-1,3-oxazinan-6-ones with excellent trans diastereoselectivity. Highlighting the versatility of the oxazinanone, a number of transformations were performed to produce a variety of protected N-H and N-methyl alpha-hydroxy- and alpha-methyl-beta-amino acids.     

Transformation of methyl N-methyl-N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetates into 4-methylamino-5-nitrosopyrimidines and 9-methylpurin-8-ones

N-Methyl-N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetic acid methyl esters under the treatment of sodium alkoxides, depending on the nature of substituents in 6 position of the pyrimidine ring, undergo ring closure and rearrangement to give 6-substituted-4-methylamino-5-nitrosopyrimidines or 9-methylpurin-8-ones.     

Synthesis of 4H-pyrazolo- and 4H-pyrrolophenothiazin-4-one derivatives

5-Methyl- and 6-methyl-2-phenyl-2H-indazole-4,7-diones were condensed with 2-aminobenzenethiol or 6-substituted-3-aminopyridine-2(1H)thiones 4 to produce a new type of 5-methyl-2-phenyl-4H-pyrazolophenothiazin-4-ones or 8-substituted-7-aza-5-methyl-2-phenyl-4H-pyrazolophenothiazin-4-one derivatives. From 6-bromo-2,5-dimethyl-1,3-diphenyl-2H-isoindole-4,7-dione and 4 8-substituted-7-aza-2,5-dimethyl-1,3-diphenyl-4H-pyrrolophenothiazin-4-one derivatives were also prepared.     

Efficient synthesis of 5-substituted-4,5-dihydro-1,2,4-triazin-6-ones and 5-substituted-1,2,4-triazin-6-ones

Treatment of methyl α-(dimethylarninomethyleneamino)carboxylates 1 (from α-amino acids and dimethylformamide dimethylacetal) with hydrazine gives 5-substituted-4,5-dihydro-1,2,4-triazin-6-ones 2 , which are smoothly dehydrogenated to 5-substituted-1,2,4-triazin-6-ones 3 with potassium permanganate in acetone/acetic acid.     

A new method for the synthesis of 6H,11H-indolo[3,2-c]-isoquinolin-5-ones/thiones and their reactions

The synthesis of 8-substituted and unsubstituted 6H,11H-indolo[3,2-c]isoquinolin-5-ones/thiones 3a-c and 4a-c and their derivatives viz, ethyl (8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)acetates 5a-c , (8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)acetyl hydrazides 6a-c , 3,5-disubstituted-pyrazoles 7a-c and 8a-c , 3-substituted-pyrazol-5-ones 9a-c and 5-(8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)methyl-1,3,4-oxadiazole-2-thiones 10a-c , also ethyl (8-substituted-11H-indolo[3,2-c]isoquinolin-5-ylthio)ace-tates 11a-c , (8-substituted-11Hindolo[3,2-c]isoquinolin-5-ylthio)acetyl hydrazides 12a-c , 3,5-disubstituted-pyrazoles 13a-c and 14a-c , 3-substituted-pyrazol-5-ones 15a-c and 5-(8-substituted-11H-indolo[3,2-c]isoquin-olin-5-yl)thiomethyl-1,3,4-oxadiazole-2-thiones 16a-c is described.     

Eco-friendly rapid synthesis of 3-substituted-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones in choline chloride based deep eutectic solvent

A series of 3-substituted-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones and 6-iodo-3-substituted-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones were synthesized in choline chloride/urea deep eutectic solvent. Substituted 2-mercapto-4(3H)-quinazolinones were synthesized from anthranilic acid or 5-iodoanthranilic acid and appropriate isothiocyanates in good to excellent yields. Isolation of final product was easy and required no further purification. Synthesis of these compounds was rapid, selective, and catalyst free, while preparation of deep eutectic solvent was easy, components are readily available, cheap, and environmentally friendly.     

COPPER-CATALYSED REARRANGEMENT OF 4-SUBSTITUTED-2,3-1H-BENZOXAZINE-1-THIONES

Abstract

4-Substituted-2,3-1H-benzoxazine-1-thiones were prepared by the treatment of the corresponding benzoxazine-1-ones with P₂S₅. The thermal rearrangement of 4-substituted-2.3-1H-benzoxazine-1-thiones, catalysed by metallic copper, yielded 4-substituted-2.3-1 H-benzthiazine-1-ones.     

4-Alkoxycarbonyl, 4-alkylthiocarbonyl and 5-alkoxycarbonyloxy derivatives of 1-substituted-3-methylpyrazol-5-ones

The reaction of 1-substituted-3-methylpyrazol-5-ones 1 with alkyl chloroformates and calcium hydroxide in dioxane have been studied. With 1-phenyl-3-methylpyrazol-5-one, the isolated product was alkyl 3-methyl-5-oxo-1-phenylpyrazole-4-carboxylate 2 but with 1-alkyl-3-methylpyrazol-5-one formation of 1-alkyl-5-alkoxycarbonyloxy-3-methylpyrazole 3 was observed. Replacement of alkyl chloroformate by bis(alkoxythiocarbonyl) sulfide results in the formation of 4-alkoxythiocarbonyl derivatives 4 in low yield with both 1-substituted-3-methylpyrazol-5-ones.