Дисертації з теми "Spiro compound"

L’électronique organique (EO) s’articule autour de l’utilisation des semi-conducteurs organiques (SCOs). Les diodes organiques électroluminescentes (OLEDs) font partie des technologies électroniques les plus matures et sont déjà présentes dans nos smartphones, ordinateurs et téléviseurs. Durant cette thèse, nous nous sommes particulièrement intéressés à l’élaboration de matrices hôtes pour la seconde génération d’OLEDs : les diodes organiques électrophosphorescentes (PhOLEDs). Deux design moléculaires différents ont été conçus avec deux objectifs différents. Le premier objectif consiste à développer de nouvelles matrices hôtes utilisant l’architecture Donneur-spiro-Accepteur pour des PhOLEDs monocouches, qui sont des dispositifs simplifiés utilisant seulement les électrodes et la couche émissive. Ces travaux ont conduit à la fabrication de PhOLEDs monocouches des trois couleurs présentes dans un pixel (rouge, vert et bleu), et des couleurs pour l’éclairage (jaune et blanc). Des records de performances ont été obtenus. Le deuxième objectif consiste à développer de nouveaux SCOs appelés nano-anneaux. Après un chapitre bibliographique analysant les performances des nano-anneaux en EO, nous présenterons une étude de structure/propriétés de nano-anneaux donneur-accepteur. Ces travaux, nous ont permis de mieux comprendre les propriétés singulières de ces composés cycliques à base de carbazoles, qui ont ensuite ont été incorporés dans des PhOLEDs multicouches pour évaluer leurs performances en tant que matrice hôtes. Ces travaux représentent les premiers exemples du domaine
Organic electronics (EO) is based on organic semiconductors (OSCs). Organic light-emitting diodes (OLEDs) are among the most mature EO technologies and are already present in our smartphones, computers and televisions. During this thesis, we were particularly interested in the development of host materials for the second generation of OLEDs: organic electrophosphorescent diodes (PhOLEDs). Two different molecular designs have been elaborated with two different objectives. The first objective was to develop new host materials using the Donor-spiro-Acceptor architecture for single-layer PhOLEDs, which are simplified devices using only the electrodes and the emissive layer. This work has enabled the fabrication of single-layer PhOLEDs in the three colours present in a pixel (red, green and blue) and in the colours used for lighting (yellow and white). Device performance records have been obtained. The second objective was to develop new SCOs, with a cylindric shape, called nanohoops. After a bibliographic chapter analysing the performance of nanohoops in EO, we present a structure/properties study of Donor-Acceptor nanohoops. This work enabled us to gain a better understanding of the unique properties of these carbazole-based nanohoops, which were then incorporated into multilayer PhOLEDs to measure their performances. This work provides the first exemples of the field

De par leur versatilité synthétique, les matériaux moléculaires pour l’électronique ou la photonique organique peuvent être conçus sur mesure afin d'intégrer, de façon optimale, divers types de dispositifs. Dans ce contexte, ces travaux de thèse se sont consacrés à l'élaboration et l'étude de composés spiro pour des applications en électronique organique. Ainsi, après un premier chapitre introductif présentant un état de l’art focalisé sur l'utilisation des composés spiro au sein de dispositifs électroniques, les deux autres chapitres seront consacrés à l'élaboration et la mise en oeuvre de nouvelles molécules organiques comportant un coeur spiro. En conséquence, le chapitre 2 sera entièrement consacré à la synthèse des molécules cibles envisagées. Il reprendra donc la fonctionnalisation d’un composé spiro largement étudié : le spirobifluorène, ainsi que les synthèses décrites de certains de ses analogues bi-hétérocycliques, et les optimisations apportées. Enfin, la présentation d'une nouvelle méthodologie de synthèse de composés à coeur spiro à partir de bis-arylcétone sera exposée et rationalisée grâce à une approche théorique. Le chapitre 3, quant à lui, rassemblera l'ensemble des caractérisations des propriétés physico-chimiques des composés préparés afin de pouvoir dégager certaines règles d'ingénierie moléculaire. De plus, la caractérisation de dispositifs électroniques incorporant nos molécules comme matériaux actifs nous permettra de mettre en avant les avantages des molécules à coeur spiro par rapport à leurs analogues linéaires
In organic electronics or photonics field, the molecular materials can be elaborated on fashion in order due to their synthetic versatility which represents a strong advantage for their optimal integration in corresponding devices. In this context, this thesis work was devoted to the development and study of spiro compounds for organic electronics applications. After a first opening chapter focusing on the state of the art of various uses of spiro compounds in molecular electronic, the two following chapters are devoted to the development and implementation of new organic molecules including a spiro node. Therefore, chapter 2 is completely devoted to the synthesis of envisioned target molecules. It resumes the functionalisation of a well-spread spiro compound: the spirobifluorene, as well as the optimized synthesis of some previously described bi-heterocyclic analogs. Finally, the presentation of a new synthesis methodology starting form bis-aryl ketones is exposed and streamlined with a theoretical approach. Concerning the chapter 3, it collects all physicochemical characterizations of the prepared compound in order to emit some simple molecular engineering rules. Moreover, the characterization of electronic devices incorporating our molecules as active materials allow us to highlight the benefits of spiro molecules by comparison to their linear analogs

This thesis is divided in two separate sections, both conducted in the Department of Chemical and Pharmaceutical Sciences under the supervision of Prof. Dr. Simonetta Benetti and Prof. Dr. Claudio Trapella. The first project aimed to demonstrate the opportunity of utilizing a new type of citrus waste, called decanter centrifuge orange waste (DCOW), to extract cellulose and other constituents of the matrix. These could be sold as either mixture or isolated compounds (or derivatives) thus avoiding environmental dangerous waste disposal. A sequence of extraction steps and pH-dependant treatments were studied in order to isolate five different products from DCOW. The choice of the solvents used for extraction was directed by economic issues as well as by the need to attain food-grade compounds. An acidic treatment was utilized in order to isolate a pectic fraction, while a basic treatment allowed purifying the cellulose fraction. α-Cellulose was successfully isolated (with a yield of 9.81% ± 0.25 on dry basis) and used to produce cellulose acetate, a well-known commercial product. The other isolated fractions were analytically characterized and consisted of polyphenols, carbohydrates and terpenes, which represent all high-value products whose further purification may results in appealing saleable products. The second project was intended to synthesize potential inhibitors of mitochondrial permeability transition pore (mPTP) complex opening, which is known to be responsible for ischemic-reperfusion injury (IRI). Up to now, only few compounds are known to directly inhibit this complex. Of them, dicyclohexylcarbodiimide (DCC) and oligomycin A were elected as drug design starting points. Since DCC is slowly hydrated in human body to form dicyclohexylurea (DCU), the latter was chosen as the real starting reference substrate for the synthesis of the target compounds. Therefore, symmetric and asymmetric ureas and thioureas were produced. Besides, some aliphatic carbamate derivatives were synthesized to better understand the influence of the rings adjacent to the carbonyl group on biological activities. Studies were also conducted to synthesize new spiro compounds mimicking oligomycin A structural core. In this case, 1-phenyl-1, 3, 8-triaza-spiro[4,5]decan-4-one template was used to produce the corresponding N-8 substituted derivatives. Almost all these derivatives were produced in reasonably high yields, using inexpensive reagents and under rather mild reaction conditions. Noticeably, preliminary results from biological characterization showed that these derivatives have both inhibitor and activator potency against mPTP opening. While the identified inhibitors may be useful for IRI treatments, alternative use of the activators as antitumor compounds was hypothesized.
Questa tesi è divisa in due progetti distinti, entrambi condotti al Dipartimento di Chimica e Scienze Farmaceutiche e sotto la supervisione della professoressa Simonetta Benetti e del professor Claudio Trapella. Il primo progetto mira a dimostrare l’opportunità di utilizzare un nuovo tipo di rifiuto agrumicolo, chiamato residuo d’arancia della centrifuga decanter (decanter centrifuge orange waste – DCOW), per estrarre la cellulosa e altri costituenti presenti all’interno matrice organica. Quest’ultimi potrebbero essere venduti sia come miscele complesse che come composti purificati (o derivati), al fine di ridurre l’impatto ambiente derivante dal progressivo deposito dello scarto agrumicolo. Sono stati studiati differenti approcci al problema, tra cui una sequenza di estrazioni con solventi organici e trattamenti a differente pH al fine di isolare cinque differenti frazioni. I solventi utilizzati durante le estrazioni sono stati selezionati tenendo in considerazione l’ipotetico costo industriale e la necessità di ottenere dei composti che potessero essere destinati anche ad un uso alimentare. Un trattamento acido è stato invece necessario per rimuovere ed isolare una frazione pectica, mentre il trattamento basico ha permesso di purificare la frazione cellulosica. Infine, l’α-cellulosa ottenuta (con una resa del 9.81 % ± 0.25 rispetto al peso secco della matrice) è stata utilizzata per produrre l’acetato di cellulosa, un noto prodotto di interesse commerciale. Nelle altre frazioni isolate, caratterizzate dal punto di vista analitico, è stata riscontrata la presenza di polifenoli, carboidrati e terpeni, tutti composti ad alto valore aggiunto, la cui purificazione potrebbe essere considerata, in futuro, per ottenere ulteriori prodotti di interesse commerciale. Il secondo progetto è stato indirizzato alla sintesi di potenziali inibitori dell’apertura del poro di transizione di permeabilità mitocondriale (mPTP), che è noto per essere responsabile dai danni da ischemia-riperfusione. Fino a questo momento, si conoscono solo pochi composti in grado di inibire questo complesso proteico. Tra questi sono presenti la dicicloesilcarbodiimmide (DCC) e l’oligomicina A le cui strutture sono state prese come punti di partenza per la costruzione dei nuovi inibitori. Poiché la DCC all’interno del corpo umano è lentamente idratata a dicicloesilurea (DCU), quest’ultima è stata selezionata come principale riferimento per la sintesi dei targets. Per questo motivo sono state sintetizzate differenti uree e tiouree simmetriche e asimmetriche. Inoltre sono stati sintetizzati due derivati carbammici per meglio comprendere l’importanza biologica di strutture cicliche adiacenti al gruppo carbonile. Per quanto riguarda la struttura dell’oligomicina A, si è optato per sintetizzare delle nuove molecole che possedessero uno spiro centro, come nel caso dell’oligomicina, ma che permettessero delle modifiche strutturali su più parti della molecola. In questo caso si è scelto l’1-fenil-1,3,8-triaza-spiro[4,5]decan-4-one, un composto commercialmente disponibile, per produrre i corrispettivi derivati sull’atomo di azoto in posizione 8. Quasi tutti i derivati sono stati sintetizzati con rese moderatamente alte, utilizzando reagenti economici e in condizioni di reazione blande. Inaspettatamente, i risultati preliminari provenienti da test biologici in vitro hanno mostrato che alcuni dei prodotti sintetizzati sembrano buoni inibitori, mentre altri sono risultati induttori dell’apertura dell’mPTP. Questi ultimi, nonostante non possano essere utilizzati nel campo del trattamento da IRI, potrebbero possedere un efficacia come composti anti-tumorali.

Les travaux décrits dans ce mémoire ont pour objet l’étude de la réactivité des ω-céto-esters acétyléniques vis-à-vis des métaux de transition. Lorsque ces composés sont traités avec une mélange Ti(OiPr)4/iPrMgBr, la formation d’alcools allyliques bicycliques est observée avec une totale diastéréosélectivité par rapport à la jonction de cycle (cis) et une configuration (E) pour la double liaison. Il a été montré que ces produits peuvent être transformés en lactone α,β-insaturé, sous-structures de produits naturels. La cycloisomérisation d’alcynyl cétones catalysées par des sels d’Ag(I) conduit à la formation de composés spiraniques. En piégeant l’intermédiaire réactionnel, la synthèse des composés vinyl-iodés correspondants a été réalisée. Si la réaction de cycloisomérisation est effectuée avec des ω-céto-esters acétyléniques, des ester α,β-insaturés sont isolés. Les produits obtenus ont ensuite été utilisés comme substrats pour la formation de systèmes tricycliques 6-5-5 et 6-6-5. Ces enchaînements de cycles sont présents dans le squelette carboné d’une grande variété de produits naturels. Les travaux décrits dans ce mémoire ont pour objet l’étude de la réactivité des ω-céto-esters acétyléniques vis-à-vis des métaux de transition. Lorsque ces composés sont traités avec une mélange Ti(OiPr)4/iPrMgBr, la formation d’alcools allyliques bicycliques est observée avec une totale diastéréosélectivité par rapport à la jonction de cycle (cis) et une configuration (E) pour la double liaison. Il a été montré que ces produits peuvent être transformés en lactone α,β-insaturé, sous-structures de produits naturels. La cycloisomérisation d’alcynyl cétones catalysées par des sels d’Ag(I) conduit à la formation de composés spiraniques. En piégeant l’intermédiaire réactionnel, la synthèse des composés vinyl-iodés correspondants a été réalisée. Si la réaction de cycloisomérisation est effectuée avec des ω-céto-esters acétyléniques, des ester α,β-insaturés sont isolés. Les produits obtenus ont ensuite été utilisés comme substrats pour la formation de systèmes tricycliques 6-5-5 et 6-6-5. Ces enchaînements de cycles sont présents dans le squelette carboné d’une grande variété de produits naturels
In this work, the reactivity of acetylenic ω-ketoesters towards different metal complexes was investigated. When acetylenic ω-ketoesters are submitted to Ti(OiPr)4/iPrMgBr, the formation of fused bicyclic γ-hydroxy-α,β-unsaturated esters was observed. The products were obtained with absolute selectivity in regard to the ring junction formed (cis) and the configuration of the double bond (E) and could be transformed into the corresponding α,β-unsaturated lactones, substructures of various natural products. When ω-ketoalkynes are used in Ag(I)-catalyzed cycloisomerization reactions, the formation of spirocyclic compounds was observed. By taking advantage of the reaction intermediates of this reaction, it was possible to isolate the corresponding spirocyclic alkenyl iodides. Performing cycloisomerization reactions with acetylenic ω-ketoesters, spirocyclic α,β-unsaturated esters are formed. We could show that these products are valuable substrates for the formation of 6-5-5- and 6-6-5-fused tricyclic systems which represent the skeleton of a large group of natural products

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This work describes firstly an efficient and regioselective method for the synthesis of a new series of 2,2,2-trifluoro-1-[4-methoxy-spiro(2H-chromen-2,1 -cycloalkan)-3-yl]ethanones from the Kabbe adducts (spiro[chroman-2,1 -cycloalkan]-4-ones). Yields of 38 % to 61 % were obtained when trifluoroacetylation reactions of mixtures of enolethers and/or acetals derived from four spiro ketones (Kabbe adducts) were performed at a temperature of 45 oC and employing anhydrous chloroform as the solvent. Subsequently, when the respective trifluoroacetylated Kabbe adducts reacted with phenylhydrazine and methylhydrazine at a 1:1 molar ratio in refluxing ethanol for 24 hours, a new series of seven examples of a novel spiro-condensed heterocyclic system, namely 1(2)-methyl(phenyl)-3-(trifluoromethyl)-1,4(2,4)-dihydro-spiro(chromen[4,3-c]pyrazole-4,n -cycloalkanes) where cycloalkanes are cyclopentane, cyclohexane and cycloheptane (n = 1) and tetrahydro-2H-pyran (n = 2) were isolated at yields of between 35 % and 51 %. NMR and X-ray diffraction techniques demonstrated clearly that reactions from methylhydrazine and phenylhydrazine were regioselective and allowed to isolate separately the 1,3- and 2,3-trifluoromethylated isomers, respectively. Subsequently, two examples of new 3-hydroxy-3-(trifluoromethyl)-3,3a-dihydro-4H-spiro(chromen[4,3-c]isoxazole-4,1 -cycloalkanes), derivated from cyclopentanone and cyclopentanone, were obtained from the reaction of 2,2,2-trifluoro-1-[4-methoxy-spiro(2H-chromen-2,1 -cycloalkan)-3-yl]ethanones with hydroxylamine hydrochloride in yields of 42% and 58%, respectively. Finally, the structures of new spiro heterocycles were determined with the aid and simultaneous application of 1H-, 13C{1H}- and 19F-NMR, X-ray monocrystal diffraction, Mass Spectrometry and DFT calculation techniques and their purity were proved by elemental analysis or High Resolution Mass Spectrometry (HRMS).
O presente trabalho descreve inicialmente um método eficiente e regiosseletivo para a síntese de uma nova série de 2,2,2-triflúor-1-[4-metóxi-espiro(2H-cromen-2,1 -cicloalcan)-3-il]etanonas a partir de adutos de Kabbe (espiro[croman-2,1 -cicloalcan]-4-onas). Rendimentos de 38% a 61% foram obtidos quando reações de trifluoracetilação de misturas de enoléteres e/ou acetais derivados de quatro espiro cetonas (adutos de Kabbe) foram realizadas a 45 ºC usando clorofórmio anidro como solvente. Subsequentemente, quando os respectivos adutos de Kabbe trifluoracetilados foram reagidos com fenilhidrazina ou metilhidrazina, em relação molar de 1:1, sob refluxo de etanol por 24 horas, uma série de sete exemplares de um novo sistema heterocíclico espiro-condensado, denominado 1(2)-metil(fenil)-3-(trifluormetil)-1,4(2,4)-diidro-espiro(chromen[4,3-c]pirazol-4,n -cicloalcanos) onde os cicloalcanos são ciclopentano, ciclohexano e cicloheptano (n = 1) e tetraidro-2H-pirano (n = 2), foi isolada em rendimentos entre 35 % e 51 %. Técnicas de RMN e de difração de raios-X demonstraram claramente que as reações a partir da metilhidrazina e da fenilhidrazina foram regiosseletivas e permitiram isolar separadamente os isômeros trifluormetilados 1,3 e 2,3, respectivamente. Em sequência, dois exemplares de novas 3-hidróxi-3-(trifluormetil)-3,3a-diidro-4H-espiro(cromen[4,3-c]isoxazol-4,1 -cicloalcanos), derivados da ciclopentanona e ciclohexanona, foram obtidos a partir da reação de 2,2,2-triflúor-1-[4-metóxi-espiro(2H-cromen-2,1 -cicloalcan)-3-il]etanonas com cloridrato de hidroxilamina em rendimentos de 42% e 58%, respectivamente. Finalmente, as estruturas dos novos espiro heterociclos foram determinadas com o auxílio e aplicação simultânea de experimentos de RMN de 1H, 13C{1H}, 19F, difração de raios-X em monocristais, Espectrometria de Massas e cálculos DFT e, a sua pureza comprovada por Análise Elementar ou por Espectrometria de Massas de Alta Resolução (HRMS).

La catalyse organométallique est l'un des piliers de la synthèse chimique moderne. Elle permet notamment la formation rapide de liaisons carbone-carbone et carbone-hétéroatome, processus les plus importants pour la fabrication des milliers de composés nécessaires à la vie contemporaine. Elle répond également aux critères d'économie d'atomes et d'énergie, et de réduction des déchets, des risques et des coûts de mise en oeuvre d'une réaction chimique.Parmi les thématiques les plus récentes de la synthèse organique, la catalyse homogène à l'or s'est imposée en seulement quelques années comme un outil synthétique très puissant. Elle autorise la génération rapide de complexité moléculaire à partir de substrats simples par l'activation d'insaturations carbonées. Durant ces études, nous avons tenté de tirer profit du caractère carbophile des complexes d'or (1) et (Ill) mais aussi de leur affinité pour certaines fonctions polaires pour transformer des hétérocycles acétyléniques en composés hétéropolycycliques dans des réactions en cascade. La réactivité complémentaire des complexes d'argent (1) a également été exploitée, ces derniers présentant de surcroît une sélectivité remarquable pour la déprotection d'éthers de méthoxybenzyle
Organometallic catalysis is a key tool of modern chemical synthesis. lts use is ubiquitous in the preparation of bulk or fine chemicals, in particular for the assembly of carbon-carbon and carbon-heteroatom bonds. Besides its overall efficiency, it responds to the responsible criteria of energy and atom economy, the reduction of waste, risk, and financial costs needed to perform a chemical reaction.ln just a few years, homogenous gold catalysis has emerged as an invaluable tool for the fast generation of molecular complexity. lndeed, it allows the strong electrophilic activation of unsaturated hydrocarbon moieties (e.g. alkynes or alienes). During this PhD thesis, we focused our studies on the use of gold's pi acidity as weil as its "classical" - but less discussed - Lewis acid character for the triggering of cascade reactions.Starting from acetylenic heterocycles, we targeted the synthesis of polycyclic compounds. The milder reactivity of silver complexes was also found useful in these reactions, as weil as in the deprotection of methoxybenzyl ethers

The main topic of this thesis is the use of organocatalysis to synthesize organic compounds enantiomerically enriched. The first matter is about the synthesis of α-amino thioester derivatives through a tandem condensation-intramolecular rearrangement-protonation, this is a conceptually novel chiral Brønsted base/ Brønsted acid catalytic method that provides a number of important synthetic building blocks in good yields and with moderate and good enantioselectivities. The second topic is concerned to the synthesis of aldols derivatives of pyridine carbaldehydes functionalized in different positions using simple amino acids derivatives as catalysts, for example L-proline, L-pyrrolidine tetrazole and so on. This is important because is necessary to found news synthetic methods to produce pyridines nucleus that are very important building block for drugs. Following it is illustrated a preliminary result of a new methodological approach to the synthesis of enantiomerically enriched cyclopentanones starting from cyclobutanones and spirocyclopentanones, it is possible to expand the ring through an organocatalysed Michael reaction. This new approach takes advantages of the introduction of the α,β-unsatured aldehyde function on cyclobutanones. Finally, supramolecular interactions by halogen bonding are described. These occurs between enatiomerically enriched aldols benzothiophene derivatives, synthesized by means of organocatalysed reactions. These kinds of interactions are strongly important in supramolecular chemistry but also in biochemistry, materials and crystal engineering.

碩士
國立臺灣師範大學
化學系
104
In my thiesis, the cinchona alkaloid derived organocatalysts were utilized for the synthesis of cyclohexanone and cyclopentanone derivatives via the covalent or non-covalent asymmetric organocatalysis. In the first part, a new class of coumarin derivatives, bearing an electrophilic and a nucleophilic site at the same time, have been developed. Cinchona alkaloid-derived chiral hydrogen bonding catalysts were utilized to carry out the [3+2] cyclization of these coumarin derivatives with 2-alkylidene indandiones. The corresponding spiro products bearing four stereocenters, including an all-carbon quaternary center, were obtained as single diastereomers with high enantioselectivity. The Michael addition intermediate was also isolated and a few control experiments have been performed to support the proposed mechanism. In second part, a cinchona-alkaloid derived chiral primary-amine-catalyzed enantioselective spirocyclohexanones derivatives is demonstrated. Both the enantiomeric forms of the trans isomer are obtained in excellent yields and enantioselectivities. Mechanistic investigations revealed two competing pathways, a concerted Diels−Alder reaction and a stepwise Michael addition, for the formation of corresponding products.

碩士
國立清華大學
化學系
90
Sequential treatment of bicyclic γ-cyano-α,β-unsaturated ketone 2, readily achieved by Robinson annulation of α-cyano ketone 1 with lithium naphthalenide (LN) and 1,4-diiodobutane or 1,5-diiodopentane gave, in one pot, spiro product 3 in a highly regioselective manner. The dienolate intermediate of the above reductive decyanation process could also be trapped with diethyl chlorophosphonate to give dienyl phosphate 4. Under Lewis acid catalysis conditions, treatment of phosphate 4 with dienophiles gave the highly functionalized Diels-Alder adduct such as compound 5. The details of the investigation into the generality and scope of the above-mentioned transformations constitute the body of this thesis.

博士
國立成功大學
化學系碩博士班
101
Part 1 Free radical reaction 1.A free radical reaction medicated by manganese(III) acetate between 2-benzoyl-1,4-benzoquiones and 1,3-dicarbonyl compounds produces benzo[c]furan-4,7-diones 34 and anthracene-1,4-diones 35 with chemoselectivity. 2.A free radical cyclization reaction mediated by Mn3+ between TsNa and N-(β-allylsulfonylpropionyl)-4-methoxy- naphthylamine 65 can produce spirolatam 75 without any 6-endo-trig product. Part 2 Heterolytic reaction 1.Highly functionalized isoxazoles can be synthesized from ethyl α- nitrocinnamates 60 and ethyl nitroacetate under basic condition.Besides, highly functionalized isoxazoles can also be synthesized from ethyl nitroacetate and aromatic aldehydes under basic condition. 3-Amidoisoxazoles 82 can also be synthesized from ethyl nitroacetate， aromatic aldehydes, morpholine and pyridinium bromide under not only one-pot but solvent-free condition. 2.Highly functionalized 2,3-dihydrofurans 34 can be synthesized by one-pot multicomponent reaction. The solvent-free condition is also effective.