Synthesis of substituted 2-ethyl-3-(4-hydrazinocarbonylphenyl)-4-quinazo-lones and 2-ethyl-3-(4-hydrazinocarbonylmethylphenyl)-4-quinazolones

Some substituted 2-ethyl-3-(4-hydrazinocarbonylphenyl)-4-quinazolones and 2-ethyl-3-(4-hydrazinocarbonylmethylphenyl)-4-quinazolones were synthesized and characterized by their sharp melting points, elemental analyses and spectral data.     

2-(3-ethyl-2,2-dimethylcyclobutyl-methyl)-4(3H)-quinazolinones

Anthranilic acid and its 5-bromo and 4-chloro derivatives react with pinanoic and pinonoic acid chlorides to give the corresponding N-acyl derivatives. The pinanoyl derivatives give the corresponding 2-(3-ethyl-2,2-dimethyl-cyclobutylmethyl)-4-(3H)-quinazolinones when refluxed in formamide. Pinanoylanthranilic acid reacts with dicyclohexylcarbodiimide to give 2-(3-ethyl-2,2-dimethylcyclobutylmethyl)benz-3,1-oxazin-4(H)-one and subsequently with hydrazine hydrate to give 3-amino-2-(3-ethyl-2,2-dimethylcyclobutylmethyl)-4(3H)-quinazolinone. Refluxing of the pinanoyl- and pinonoylanthranilic acids with acetic anhydride gives acetylanthranilic acid, and pinonoylanthranilic acid gives 4(3H)-quinazolinone with formamide.Riga Technical University, Riga LV-1658, Latvia; e-mail: marina@osi.lanet.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 811–817, June, 1999.     

Essential oil deterpenation by solvent extraction using 1-ethyl-3-methylimidazolium 2-(2-methoxyethoxy) ethylsulfate ionic liquid

Taking into account that heat application can have undesirable effects in essential oil properties, liquid extraction comes up as a promising process instead of distillation for citrus oil deterpenation. In this work the suitability of using the ionic liquid 1-ethyl-3-methylimidazolium 2-(2-methoxyethoxy) ethylsulfate as a solvent for the extraction of linalool from citrus essential oil (which has been simulated as a mixture of limonene and linalool) has been analyzed. Liquid–liquid equilibrium data at three different temperatures (298.15 K, 308.15 K and 318.15 K) have been reported and successfully correlated using NRTL model. The best results were achieved using α = 0.1 for the systems at 298.15 K and 308.15 K and α = 0.2 at 318.15 K. The solute distribution ratio has showed values close to one and high values of selectivity have been achieved.     

X-ray absorption spectroscopic studies of chromium(V/IV/III)- 2-ethyl-2-hydroxybutanoato(2-/1-) complexes

Structures of the complexes [Cr(V)O(ehba)(2)](-), [Cr(IV)O(ehbaH)(2)](0), and [Cr(III)(ehbaH)(2)(OH(2))(2)](+) (ehbaH(2) = 2-ethyl-2-hydroxybutanoic acid) in frozen aqueous solutions (10 K, [Cr] = 10 mM, 1.0 M ehbaH(2)/ehbaH, pH 3.5) have been determined by single- and multiple-scattering fitting of X-ray absorption fine structure (XAFS) data. An optimal set of fitting parameters has been determined from the XAFS calculations for a compound with known crystal structure, Na[Cr(V)O(ehba)(2)] (solid, 10 K). The structure of the Cr(V) complex [Cr(V)O(ehba)(2)](-) does not change in solution in the presence of excess ligand. Contrary to the earlier suggestions made from the kinetic data (Ghosh, M. C.; Gould, E. S. J. Chem. Soc., Chem. Commun. 1992, 195-196), the structure of the Cr(IV) complex (generated by the Cr(VI) + As(III) + ehbaH(2) reaction) is close to that of the Cr(V) complex (five-coordinate, distorted trigonal bipyramidal) and different from that of the Cr(III) complex (six-coordinate, octahedral). For both Cr(V) and Cr(IV) complexes, some disorder in the position of the oxo group is observed, which is consistent with but not definitive for the presence of geometric isomers. The structure of the Cr(IV) complex differs from that of Cr(V) by protonation of alcoholato groups of the ligands, which leads to significant elongation of the corresponding Cr-O bonds (2.0 vs 1.8 A). This is reflected in the different chemical properties reported previously for the Cr(IV) and Cr(V) complexes, including their reactivities toward DNA and other biomolecules in relation to Cr-induced carcinogenicity.     

Synthesis and polymerization of (R)-(+)-2-methyl-2-ethyl-3-propiothiolactone

(R)-(+)-2-Methyl-2-ethyl-3-propiothiolactone was synthesized by debenzylation and cyclization of (?)-2-methyl-2-ethyl-3-benzylmercaptopropionyl chloride under the conditions of Friedel-Crafts synthesis, and by dehydration of (R)-(+)-2-methyl-2-ethyl-3-mercaptopropionic acid with dicyclohexyl carbodiimide. The configuration of the (+)-propiothiolactone was determined by chemical interconversion with (?)-2-methyl-2-ethylsuccinic acid, the absolute configuration of which is known to be (R). The polymerization of (R)-(+)-2-methyl-2-ethyl-3-propiothiolactone was performed in bulk with tetrabutylammonium versatate as catalyst. The specific rotation of the polymer ([α]_D +151.7°) compared with the rotation of the low molecular weight model compound (R)-(+)-2-methyl-2-ethyl-3-acetylmercapto-thiolpropionic acid methyl ester ([α]D +55.0°) shows a significant enhancement, thus suggesting the possibility of the presence of rigid conformations in polymer chain.     

LDA-catalyzed cycloisomerization of 2-(2-propynyloxy)ethyl iodides leading to 3-(iodomethylene)tetrahydrofurans

LDA catalyzes cycloisomerization of 2-(2-propynyloxy)ethyl iodides to give 3-(iodomethylene)tetrahydrofurans. The reaction is proposed to proceed through a mechanism involving exo-cyclization of an alkynyllithium intermediate and protonation of the resulting alkylidene carbenoid by the starting iodide. [reaction: see text]     

Design and synthesis of (E)-4-((3-ethyl-2,4,4-trimethylcyclohex-2-enylidene)methyl)benzoic acid

(E)-4-((3-Ethyl-2,4,4-trimethylcyclohex-2-enylidene)methyl)benzoic acid, 6, was synthesized in 87% starting from β-cyclocitral. The target compound 6 was synthesized starting from 1 via a Grignard reaction to form alcohol 2. Compound 2 was converted to Wittig salt 3 by treatment with aldehyde 4 in butyllithium and hexane at −78 °C to form ester 5. Ester 5 was saponified and, following acidification, acid 6 was isolated as white solid yield 87%.     

3-乙基-2-丙基喹啉衍生物的合成工艺研究

以芳胺和正丁醛为原料,对甲基苯磺酸(TsOH)为促进剂,采用"一锅法"合成了3-乙基-2-丙基喹啉衍生物,系统地考察了原料比例、溶剂以及芳胺上取代基对反应的影响,比较了不同的质子酸促进剂对喹啉衍生物产率以及选择性的影响,并对产物进行了核磁共振表征.实验结果表明当用对甲基苯磺酸(TsOH)为促进剂时,3乙基-2-丙基喹啉收率可达到59%,同时生成40%N-丁基苯胺;磷钼酸、浓硫酸也可以选择性地得到喹啉衍生物,但收率较低,分别只有28%和24%.同时,考察了苯胺环上取代基对喹啉收率的影响,当苯环上有供电子基时,有利于喹啉的生成,而吸电子基则不利于喹啉的生成.并推测了反应机理.     

Synthesis of 1-(2-ethyl-3-indolyl)-1-(3-pyridyl)ethylene and related ellipticine analogues

Indole, 2-methylindole, and 3-etliylindole have been condensed with acetyl- and propionylpyridine, respectively. When propionylpyridine was used as the reactant, the product always was a 1-(pyridyl)-1-indoly[propylene. Condensation of 2-substituted indoles with 3-acetylpyridine gave similar products, whereas a similar condensation with 4-acetylpyridine gave 1,2-bis(3-indolyl)-1-(4-pyridyl)ethanes (e.g. 7a ). Condensation of unsubstituted indole with 3-or 4-acetylpyridine respectively, gave 1,1-bis(3-indolyl)-1-(pyridyl)ethanes (e.g. 6c ).     

Mild synthesis of 5-(9-ethyl-9H-carbazol-3-yl)-N-aryl-1,3,4-thiadiazol-2-amines

An efficient synthetic method for heterocycles containing both carbazole and 1,3,4-thiadiazole moieties is described. 9-Ethyl-9H-carbazol-3-carbaldehyde reacted with 4-arylthiosemicarbazides, with acetic acid as catalyst, to give 1-(9-ethyl-9H-carbazol-3-yl)methylene-4-arylthiosemicarbazides, which were further treated with manganese dioxide at room temperature in acetone to give 5-(9-ethyl-9H-carbazol-3-yl)-N-aryl-1,3,4-thiadiazol-2-amines in good to high yield. This procedure has the advantages of mild conditions, easy separation, and simple manipulation.     

Tuning delocalization in the radical cations of 1,4-bis[4-(diarylamino)styryl]benzenes, 2,5-bis[4-(diarylamino)styryl]thiophenes, and 2,5-bis[4-(diarylamino)styryl]pyrroles through substituent effects

Radical cations have been generated for 10 bis[4-(diarylamino)styryl]arenes and heteroarenes to investigate the effect of the electron-richness of the terminal groups and of the bridging (hetero)arene on delocalization. The intervalence charge-transfer bands of these radical cations vary from weak broad Gaussians, indicative of localized class-II mixed-valence species, to strong relatively narrow asymmetric bands, characteristic of delocalized class-III bis(diarylamino) species, to narrow symmetric bands in cases where the bridge contribution to the singly occupied molecular orbital is largest. Hush analysis of these bands yields estimates of the electronic coupling varying from 480 cm(-1) (electron-poor bridge, most electron-rich terminal aryl groups) to 1000 cm(-1) (electron-rich bridge, least electron-rich termini) if the diabatic electron-transfer distance, R(ab), is equated to the N-N separation. Computational and electron spin resonance (ESR) evidence for displacement of the diabatic states into the bridge (reduced R(ab)) suggests that these values are underestimates and that even more variation is to be expected through the series. Several dications have also been studied. The vis-NIR absorption of the dication of (E,E)-1,4-bis{4-[bis(4-n-butoxyphenyl)amino]styryl}-2,5-dicyanobenzene is seen at an energy similar to that of the strongest band in the spectrum of the corresponding weakly coupled monocation, with approximately twice the absorptivity, and its ESR spectrum suggests essentially noninteracting radical centers. In contrast, the electronic spectra of class-III monocations show no clear relationship to those of the corresponding dications, which ESR reveals to be singlet species.     

Convenient synthesis and antitumor evaluation of some new 9-ethyl-3-(hetaryl)carbazoles

Abstract

In continuing our efforts to develop new potent anticancer candidates, a new series of 9-ethylcarbazoles carrying at position 3 various heterocyclic substituents such as 2-imino-2H-chromenes 5a–e, 2-oxo-2H-chromenes 6a–e, 3-imino-3H-benzo[f]chromene 8, 3-oxo-3H-benzo[f]chromene 9, 2-pyridones 11, 14, pyrazole 19, pyrimidine 23, pyrido[1,2-a]pyrimidine 27, 2H-pyran-2-one 30, and pyrano[2,3-d]pyrimidinetrione 34 were efficiently synthesized, characterized and evaluated for their in vitro antitumor activity. The mechanism for the synthesis of compounds was also discussed. Most of the synthesized compounds were displayed the considerable anticancer activities against three human tumor cells lines, in particular, colon carcinoma (HCT-116), hepatocellular carcinoma (HepG-2) and breast cancer (MCF-7). Compound 6d proves as most active molecule in this study with special effectiveness against the human HCT-116 and HepG-2 as its IC₅₀ values are 1.50, 0.90?μM, respectively, when doxorubicin is compared. Compound 34 was also found to have high activity against HepG-2, HCT-116 and moderate activity against MCF-7.     

Synthesis and diels-alder reactions of (S)-3-chloro and (S)-3-ethyl-2-p-tolylsulfinyl-1,4-benzoquinones

The synthesis of the title compounds in enantiomerically pure form is described. Their cycloadditions with cyclopentadiene and 2,3-dimethyl-1,3-butadiene in the presence of ZnBr₂ take place on the unsubstituted dienophilic double bond C₅-C₆ giving access to optically active 4a,5,8,8a-tetrahydronaphthoquinones with a diastereoisomeric excess ranging from 40 to 72%.     

Pd-catalyzed synthesis of 3-(diarylmethylene)-2-oxindoles and 3-(arylmethylene)-2-oxindoles

An efficient method for the stereoselective synthesis of 3-(diarylmethylene)-2-oxindoles and 3-(arylmethylene)-2-oxindoles via carbopalladation is described. In this approach, an Ugi-4-component reaction (4-CR) adduct was used as the starting material. A one-pot sequence involving intermolecular carbopalladation C-H activation/C-C bond formation efficiently afforded the oxindole derivatives.     

Lithiation of 3-(Acylamino)-2-unsubstituted-, 3-(Acylamino)-2-ethyl-, and 3-(Acylamino)-2-propyl-4(3H)-quinazolinones: Convenient Syntheses of More Complex Quinazolinones(1)

3-(Pivaloylamino)- and 3-(acetylamino)-4(3H)-quinazolinones react with alkyllithium reagents to give 1,2-addition products in very good yields. Lithiation takes place with LDA and is regioselective at position 2. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding substituted derivatives in very good yields. Reactions of the lithium reagents with iodine give oxidatively dimerized cyclic structures. 3-(Pivaloylamino)- and 3-(acetylamino)-2-ethyl-4(3H)-quinazolinones and 3-(pivaloylamino)- and 3-(acetylamino)-2-propyl-4(3H)-quinazolinones are lithiated at the benzylic position with LDA. The lithium reagents so produced also react with a variety of electrophiles to give the corresponding 2-substituted-4(3H)-quinazolinone derivatives in very good yields. However, lithiation of 3-(acylamino)-2-(1-methylethyl)-4(3H)-quinazolinones was unsuccessful, as were lithiations of compounds having a diacetylamino group at position 3. The amide groups have been cleaved in good yield under basic or acidic conditions from some of the products to provide access to the free amino compounds.     

Asymmetric synthesis of (-)-eburnamonine and (+)-epi-eburnamonine from (4S)-4-ethyl-4-[2-(hydroxycarbonyl)ethyl]-2-butyrolactone.

The key chiral nonracemic 4,4-disubstituted 2-butyrolactone carboxylic acid, (S)-4, is readily accessible via an efficient and stereospecific dirhodium(II) tetraacetate catalyzed tertiary C-H insertion reaction of the diazomalonate (S)-5. The coupling of the acid (S)-4 with tryptamine produces the amide (S)-3, which is then transformed into the aldehyde 23 and hydroxy-lactam 24. Acid-mediated Pictet-Spengler cyclization of 23 and 24 produces the tetracyclic indole lactams (1S,12bS)-25a and (1S,12bR)-25b. Compounds 25a and 25b are converted, via the lactam alcohols 30a and 30b, to (-)-eburnamonine (1a) and (+)-epi-eburnamonine (1b).     

Stereospecific [2+2] autophotocycloaddition in the dimeric complex of 18-crown-6 ether styryl dye bearing N-(3-ammoniopropyl) substituent

New 18-crown-6 ether styryl dye of the 4-pyridine series bearing N-(3-ammoniopropyl) substituent has been synthesized. In MeCN, the dye forms a stable dimeric complex of the syn-head-to-tail type due to the complexation of the ammonium group of one molecule with the crown ether fragment of another. In the dimeric complex, the ethylene bonds of the molecules are close in space and antiparallel, which promotes an efficient stereospecific [2+2] autophotocycloaddition to yield the only rctt-isomer of 1,2,3,4-tetrasubstituted cyclobutane. The cyclobutane derivative structure was confirmed by NMR spectroscopy and X-ray diffraction.     

基于N-乙基咔唑-2-乙烯基-8-羟基喹啉锌的黄绿色有机电致发光器件的性能

通过用一种既具有空穴传输特性又具有发光特性的新型荧光染料N-乙基咔唑-2-乙烯基-8-羟基喹啉锌((E)-2-(2-(9-ethyl-9H-carbazol-3-yl)vinyl) quinolato-zinc, CzHQZn)作为受主, 制备了结构为ITO/2T-NATA (30 nm)/CBP: 6%Ir(ppy)3:wCzHQZn(20 nm)/Alq3(50 nm)/LiF/Al(ITO: indium-tin oxide, 2T-NATA: 4,4',4'-{N,N-(2-naphthyl)-N-phenylamino}-triphenylamine, CBP: 4,4-N,N'-dicarbazole-biphenyl, Ir(ppy)3: factris (2-phenylpyridine) iridium, Alq3: tris(8-quinolinolato) aluminum; w 是CzHQZn 的质量分数)的黄绿色有机电致发光器件(OLEDs). 研究了掺杂体系在不同掺杂浓度(w=5%、10%、12%、15%)时的电致发光(EL)特性. 结果表明, CzHQZn 掺杂浓度为10%的器件在11 V 电压下实现了黄绿光发射, 色坐标为(0.4045, 0.5113), 最大发光亮度为16110 cd·m-2; 而在7 V电压下的最大发光效率为2.19 cd·A-1, 最大外量子效率为0.775%.     

2-(p-取代苯乙烯基)噻唑碘盐的电子光谱研究

本文测定八种2-(p-取代苯乙烯基)噻唑碘盐染料的电子光谱。研究其吸收光谱的λ_(max)与取代基常数σ之间的定量关系,以λ_(max)值对Δσ(σρ-σm)作图呈线性趋势。并发现这些染料吸收带的溶剂效应符合 Nicol 理论。