New luminescent 2-methoxy-6-(4-methoxy-phenyl)-4-p-tolyl-nicotinonitrile: Synthesis, crystal structure, DFT and photophysical studies

In the current communication, we report the synthesis, spectroscopic, crystal structure, DFT and photophysical studies of a new nicotinonitrile derivative, viz. 2-methoxy-6-(4-methoxy-phenyl)-4-p-tolyl-nicotinonitrile (2) as a potential blue light emitting material. The compound 2 was synthesized in good yield via a simple route. The acquired spectral and elemental analysis data were in consistent with the chemical structure of 2. The single crystal study further confirms its three dimensional structure, molecular shape, and nature of short contacts. Its DFT calculations reveal that compound 2 possesses a non-planar structure and its theoretical IR spectral data are found to be in accordance with experimental values. In addition, its UV visible and fluorescence spectral measurements prove that the compound exhibits good absorption and fluorescence properties. Also, it shows positive solvatochromic effect when the solvent polarity was varied from non-polar to polar. (c) 2014 Elsevier B.V. All rights reserved.

Síntese e transformação de 4-quinolonas e quinolinas

Compostos do tipo quinolin-4(1H)-ona e quinolina estão presentes em diversas moléculas biologicamente ativas, desde alcalóides naturais a fármacos sintéticos disponíveis comercialmente, sendo que, as quinolin-4(1H)-onas destacam-se essencialmente pela sua atividade antibiótica de largo espectro. Este tipo de compostos têm sido alvo de intensa pesquisa na procura de novas moléculas com potencial aplicação na indústria farmacêutica. Nesta dissertação estabeleceram-se novos métodos de síntese de quinolin-4(1H)- onas e quinolinas e estudou-se a sua reatividade em algumas transformações químicas. No primeiro capítulo apresenta-se uma breve revisão bibliográfica sobre a ocorrência natural, atividade biológica e métodos de síntese de (E)-2- estirilquinolin-4(1H)-onas e acridin-9(10H)-onas. Seguidamente, descreve-se a síntese de novas (E)-2-estirilquinolin-4(1H)-onas a partir da ciclização de (E)- N-(2-acetilfenil)-3-arilacrilamidas, que são obtidas através da reação da 2’- aminoacetofenona com derivados do ácido cinâmico. Neste capítulo estão também descritas as transformações das (E)-2-estirilquinolin-4(1H)-onas em acridin-9(10H)-onas através de reações de Diels-Alder com a Nmetilmaleimida. No entanto, antes de se proceder ao estudo da reação de Diels-Alder foi necessário efetuar a proteção do grupo amina da 4-quinolona para evitar reações secundárias na reação de cicloadição. O estudo da proteção direta do grupo amina das (E)-2-estirilquinolin-4(1H)-onas conduziu à sintese de derivados da 2-estiril-4-metoxiquinolina como produtos secundários. A falta de regiosseletividade na reação de proteção levou a uma alteração da estratégia e as (E)-2-estiril-1-metilquinolin-4(1H)-onas foram sintetizadas a partir da reação de metilação das (E)-N-(2-acetilfenil)-3-arilacrilamidas seguida de ciclização in situ. As reações foram efetuadas também sob irradiação com micro-ondas e verificou-se que a principal vantagem desta tecnologia está relacionada com a diminuição drástica do tempo de reação. O segundo capítulo centra-se no estudo de reações catalisadas por paládio. Apresenta-se uma breve revisão bibliográfica sobre a ocorrência, propriedades biológicas e métodos de síntese de (E)-3-estirilquinolin-4(1H)-onas e furo[3,2- c]quinolinas. Seguidamente, descreve-se a síntese da 3-iodoquinolin-4(1H)- ona a partir da reação da 2’-aminoacetofenona com o formato de metilo, seguida de iodação na posição 3. A 3-iodoquinolin-4(1H)-ona será usada como precursor de novas (E)-3-estirilquinolin-4(1H)-onas através de reações de Heck com derivados do estireno. Verificou-se, no entanto, que a reação conduzia a baixos rendimentos e a estratégia utilizada para contornar esta situação foi a proteção do grupo amina da quinolona de partida, levando assim à sintese de novas (E)-3-estiril-1-metilquinolin-4(1H)-onas em bons resultados. Em alguns casos, as reações de Heck deram origem a derivados do produto secundário ramificado, verificando-se que a reação procede por duas vias mecanísticas. Este estudo foi também efetuado sob irradiação com microondas, no entanto, verificou-se que neste caso esta tecnologia conduz a uma diminuição do tempo, mas também a uma diminuição dos rendimentos. Estudou-se também a reatividade da 3-iodoquinolin-4(1H)-ona com derivados de arilacetileno em reações de Sonogashira, tendo-se estabelecido novas rotas de síntese de 2-arilfuro[3,2-c]quinolinas e, em alguns casos, de 2-aril-3- (feniletinil)furo[3,2-c]quinolinas como produtos secundários. A 3-iodo-1- metilquinolin-4(1H)-ona foi também usada como reagente de partida em reações de Sonogashira com o fenilacetileno levando à formação de novas 2- fenil-5-metilfuro[3,2-c]quinolin-4(5H)-onas. No terceiro capítulo apresenta-se uma breve revisão bibliográfica sobre a ocorrência natural, atividade biológica e métodos de síntese de pirrolo[3,2- c]quinolinas e descreve-se a síntese de novos derivados destes compostos usando a 4-cloro-3-iodoquinolina como sintão. Assim, fez-se reagir a 4-cloro-3- iodoquinolina, preparada a partir da 3-iodoquinolin-4(1H)-ona, em reações de Sonogashira, levando ao estabelecimento de novas rotas de síntese de 3- (ariletinil)-4-cloroquinolinas. Seguidamente estudou-se a reatividade das 3- (ariletinil)-4-cloroquinolinas em reações de substituição nucleofílica com várias aminas, levando à formação das intermediárias aminoquinolinas que após ciclização conduzem à síntese das novas pirrolo[3,2-c]quinolinas. Em alguns casos estes compostos foram também sintetizados num só passo usando como precursor as 3-(ariletinil)-4-cloroquinolinas, embora em piores rendimentos. Neste capítulo é também testada a reatividade da 3-(ariletinil)-4- cloroquinolina e da 4-cloro-3-iodoquinolina com a azida de sódio, tendo-se obtido as 4-aminoquinolinas correspondentes. Todos os novos compostos sintetizados foram caracterizados estruturalmente recorrendo a estudos de espectroscopia de ressonância magnética nuclear (RMN), incluindo espectros de 1H e 13C e estudos bidimensionais de correlação espectroscópica homonuclear e heteronuclear e de efeito nuclear de Overhauser (NOESY). Foram também efectuados, sempre que possível, espectros de massa (EM) e análises elementares ou espectros de massa de alta resolução (EMAR) para todos os novos compostos sintetizados.

Solid-state compounds of 4-methoxybenzylidenepyruvate and cinnamylidenepyruvates with thorium (IV) - Preparation and thermal studies

By close control of experimental variables affecting precipitation, solid-state compounds of the type Th(OH)(m)L4-m.nH(2)O, where L stands for 4-methoxy-benzylidenepyruvate, cinnamylidenepyruvate or 4-dimethylaminocinnamylidene-pyruvate; m=0 to 3 and n=0.5-3 were isolated. Chemical analysis, TG, DTG, DSC and X-ray powder diffractometry have been employed to characterize and to study the thermal behavior of these compounds in dynamic air atmosphere. In all cases, hydration water is slowly lost between 30 and 160degreesC; a continuous, slow rate, mass loss is observed thereafter and beyond 280-400degreesC the rate of decomposition/oxidation increased rapidly, to give ThO2 as the final product, beginning at 412-510degreesC. The results associated with the hydroxo-compounds indicate that the loss of constitution water (OH ions) and the decomposition / oxidation of the organic moieties occur as simultaneous process.

Effect of non-steroidal anti-inflammatory drugs (NSAID) on the histamine release induced by compound 48/80 and cardiac anaphylaxis in guinea-pig isolated heart

Histamine release from guinea pig heart treated with compound 48/80 was potentiated by the cyclooxygenase inhibitors indomethacin and piroxicam but not by aspirin or phenylbutazone. This differential effect suggests that the potentiation is not merely due to an inhibition of prostaglandin synthesis. Piroxicam potentiated the histamine release induced by cardiac anaphylaxis whereas indomethacin reduced this effect. The SRS-A antagonist FPL 55712 inhibited histamine release induced by cardiac anaphylaxis, but not that evoked by compound 48/80, and also prevented the potentiation due to indomethacin and piroxicam. In total, these data suggest that the potentiation of histamine release by piroxicam and indomethacin is probably due to a diversion of arachidonic acid metabolism from the cyclooxygenase to the lipoxygenase pathways. The resulting lipoxygenase products may then regulate histamine release, with the secretion due to antigen being more sensitive to such modulation than that evoked by compound 48/80.

Studies in terpenoids. Part XXXI. Synthesis of pyrocurzerenone, a furosesquiterpenoid from Curcuma zedoaria

7-Acetonyloxy-5-methyl--tetralone (Vc) was cyclodehydrated to 7,8-dihydro-1,5-dimethylnaphtho[2,1-b]furan-9(6H)-one (VIa), the structure of which was established by an independent synthesis from methyl 4-(4-acetonyloxy-2-methylphenyl)butyrate (IXd). Similarly, 7-acetonyloxy-2,5-dimethyl--tetralone (Vf), synthesized via 4-(5-isopropyl-4-methoxy-2-methylphenyl)-2-methylbutyric acid (XIIb) and 7-methoxy-2,5-dimethyl--tetralone (Vd), was cyclodehydrated to 7,8-dihydro-1,5,8-trimethylnaphtho[2,1-b]furan-9(6H)-one (VIb), which on reduction and dehydration furnished pyrocurzerenone (6,7-dihydro-1,5,8-trimethylnaphtho[2,1-b]furan)(I). The deisopropylation and cyclodehydration of (XIIb) to (Vd) were effected in one step by treatment with polyphosphoric acid.

Enantiodivergent Formal Total Synthesis of Aspercyclide C from L-(+)-Tartaric Acid

The enantiodivergent formal syntheses of both enantiomers of aspercyclide C is accomplished. Starting from L-(+)-tartaric acid, the key protected allylic alcohol, (3R,4R)-4-(methoxy-methoxy) non-1-en-3-ol is prepared, and is then elaborated into both enantiomers of 3-(4-methoxybenzyl)oxy]non-1-en-4-ol via Mitsunobu inversion. Esterification with a known biaryl acid, followed by ring-closing metathesis and deprotection completes the syntheses.

Total synthesis of substituted (±)-6,6-dimethyl-B-norestra-1,3,5(10)-trien-17?-ols and their 9?-isomers

Total syntheses of (±)-1,4-dimethoxy-6,6-dimethyl-B-norestra-1,3,5(10)-trien-17?-ol(11a), (±)-2,3-dimethoxy-6,6-dimethyl-B-norestra-1,3,5(10)-trien-17?-ol (11b), and (±)-3-methoxy-6,6-dimethyl-B-norestra-1,3,5(10)trien-17?-ol (11c), have been carried out starting from 4,7-dimethoxy-3,3-dimethylindan-1-one (1), 5,6-dimethoxy-3,3-dimethylindan-1-one (2), and 4?-methoxy-3-methylbut-2-enophenone (4), respectively. Generally, it is found that the intermediate 6,6-dimethyl-B-norestra-1,3,5(10),8-tetraen-17?-ols (10), on lithium�liquid ammonia reduction, yield a mixture of 8?,9?- and 8?,9?-trienols, (11) and (12) respectively, in the ratio 1 : 1. This is due to the comparable stabilities of these two isomers. However, the reduction carried out in presence of aniline affords a higher percentage of the 8?,9?-trienol (11). The assignment of configurations is made by chemical and 1H n.m.r. analysis. Catalytic hydrogenation of the tetraenols (10) is shown to proceed via initial isomerisation to the corresponding 6,6-dimethyl-B-norestra-1,3,5(10),9(11)-tetraen-17?-ols (26), followed by hydrogenation from the ?-side to give, exclusively, the 8?,9?-trienols (12).

Tertiary amine-based glutathione peroxidase mimics: some insights into the role of steric and electronic effects on antioxidant activity

In this work, several tertiary amine-based diaryl diselenides were synthesized and evaluated for their glutathione peroxidase (GPx)-like antioxidant activities using hydrogen peroxide, tert-butyl hydroperoxide and cumene hydroperoxide as substrates and thiophenol (PhSH) and glutathione (GSH) as co-substrates. A comparison of the GPx-like activity of 4-methoxy-substituted N,N-dialkylbenzylamine-based diselenides with that of the corresponding 6-methoxy-substituted compounds indicates that the activity highly depends on the position of the methoxy substituent. Although the methoxy group at 4- and 6-position alters the electronic properties of selenium, the substitution at the 6-position provides the required steric protection for some of the key intermediates in the catalytic cycle. A detailed experimental and theoretical investigation reveals that the 6-methoxy substituent prevents the undesired thiol exchange reactions at the selenium centers in the selenenyl sulfide intermediates. The 6-methoxy substituent also prevents the formation of seleninic and selenonic acids. When PhSH is used as the thiol co-substrate, the 4-methoxy-substituted diselenides exhibit GPx-like activity similar to that of the parent compounds as the 4-methoxy substituent does not block the selenium center in the selenenyl sulfide intermediates from thiol exchange reactions. In contrast, the 4-methoxy substituent significantly enhances the GPx-like activity of the diselenides when glutathione (GSH) is used as the co-substrate. (C) 2012 Elsevier Ltd. All rights reserved.

C-13-H-1 dipolar couplings for probing rod-like hydrogen bonded mesogens

Hydrogen bonding is the most important non-covalent interaction utilised in building supramolecular assemblies and is preferred often as a means of construction of molecular, oligomeric as well as polymeric materials that show liquid crystalline properties. In this work, a pyridine based nematogenic acceptor has been synthesized and mixed with non-mesogenic 4-methoxy benzoic acid to get a hydrogen bonded mesogen. The existence of hydrogen bonding between the pyridyl unit and the carboxylic acid was established using FT-IR spectroscopy from the observation of characteristic stretching vibrations of unionized type at 2425 and 1927 cm(-1). The mesogenic acceptor and the complex have been investigated using C-13 NMR in solution, solid and liquid crystalline states. Together with the 2D separated local field NMR experiments, the studies confirm the molecular structure in the mesophase and yield the local orientational order parameters. It is observed that the insertion of 4-methoxy benzoic acid not only enhances the mesophase stability but also induces a smectic phase due to an increase in the core length of the hydrogen bonded mesogen.

A new synthesis of Entacapone and report on related studies

A new synthesis of the catechol-O-methyltransferase (COMT) inhibitor, entacapone (E-isomer) has been achieved under mild conditions by amine-mediated demethylation of the precursor 2-Cyano-3-(3- hydroxy-4-methoxy-5-nitrophenyl) prop-2-eneamide, wherein the methoxyl group adjacent to a nitro group gets demethylated under nucleophilic attack. Similar demethylation was achieved on ethyl 2-cyano-3-(3, 4-dimethoxy-5-nitrophenyl) prop-2-enoate, 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethylprop-2-enamide, ethyl 2-cyano-3-(3-hydroxy-4-methoxy-5-nitrophenyl) prop-2-enoate and ethyl 2-cyano-3-(4-methoxy-3-nitrophenyl) prop-2-enoate. The scope of demethylation has been studied. Analogues of ethyl 2-cyano-3-(3, 4-dimethoxy-5-nitrophenyl) prop-2-enoate wherein a methoxyl group is not adjacent to a NO (2) group are unaffected and phenolic derivatives yield the amine salts. Entacapone has been converted to salts with organic bases. The crystal structure of the isomer of entacapone (Z-isomer), a significant human metabolite of E-isomer has been established. NMR methods for deriving E and Z geometry and other similar molecules have been successfully established, mainly by studying the proton coupled C-13 spectra. Preliminary studies reveal in vitro activity for some compounds against tuberculosis (TB) and dengue.

Oxy anion-accelerated rearrangements

The alkali metal salts of 1,5-hexadien-3-ols undergo accelerated Cope rearrangements to the enolates of δ, ε-unsaturated carbonyl compounds. The generality of the rearrangement was investigated in numerous systems, particularly acyclic cases, and the effect of changes in substituents, counterions, solvents, and geometrical structures were noted and discussed. Applications of this methodology in synthesis included the synthesis of the insect pheromone frontalin, the preparation of selectively monoprotected 1,6-dicarbonyl compounds from 4-methoxy- and 4-phenylthio-1,5-hexadien-3-ols, and the construction of complex ring structures such as a D-homo-estratetraenone derivative.

Thermochemical estimates of the energetics of anionpromoted alkoxide fragmentations were made, and in all cases heterolytic cleavage was favored over hemolytic cleavage by 8.5-53 kcal/mol. The implication of these and other thermochemical estimates is that the anionic oxy-Cope rearrangement occurs via a concerted mechanism rather than a dissociation-recombination process. The concepts of anion-induced bond weakening were successfully applied to an accelerated [1,3]-shift of a dithiane fragment in a cyclohexenyl system. Trapping experiments demonstrated that > 85% of the [1,3]-shift occurred within a solvent cage. Attempts at promoting an intramolecular ene reaction using the potassium salts of 2,7-octadien-1-o1 and 2,8-nonadien-1-o1 were unsuccessful. A general review of anion-promoted bond reorganizations and anion substituent effects is also presented.

一种新型芴类衍生物的光谱性质研究

合成了具有大π共轭性的对称型芴类衍生物9，9-二（2-乙基已基）-2，7-（2-（4-甲氧基）苯-2，1-乙烯基）芴（简写为MO-F1u—MO）。通过元素分析、质谱、紫外-可见光谱和红外光谱对其进行了表征。测试了该染料在乙腈、二氯甲烷、四氢呋喃和正己烷4种不同极性溶剂中的线性吸收光谱和单光子荧光谱。结果发现溶剂效应对吸收光谱和荧光光谱表现出不同程度的影响，对产生这些光谱行为的主要原因进行了讨论。