RESUMO
Achieving the goal of generating all of the world's energy via renewable sources and significantly reducing the energy usage will require the development of novel, abundant, nontoxic energy conversion materials. Here, a cost-efficient and scalable continuous flow synthesis of Cs3Cu2I5 nanocrystals is developed as a basis for the rapid advancement of novel nanomaterials. Ideal precursor solutions are obtained through a novel batch synthesis, whose product served as a benchmark for the subsequent flow synthesis. Realizing this setup enabled a reproducible fabrication of Cs3Cu2I5 nanocrystals. The effect of volumetric flow rate and temperature on the final product's morphology and optical properties are determined, obtaining 21% quantum yield with the optimal configuration. Consequently, the size and morphology of the nanocrystals can be tuned with far more precision and in a much broader range than previously achievable. The flow setup is readily applicable to other relevant nanomaterials. It should enable a rapid determination of a material's potential and subsequently optimize its desired properties for renewable energy generation or efficient optoelectronics.
RESUMO
ß-Aminophosphonates obtained by the Michael addition of primary amines to the double bond of diethyl vinylphosphonate proved to be suitable starting materials (amine components) in the Kabachnik-Fields reaction with formaldehyde and dialkyl phosphites or secondary phosphine oxides to afford N-phosphonylmethyl- and N-phosphinoylmethyl-ß-aminophosphonates. On the other hand, the starting aminophosphonates were modified by N-acylation using acid chlorides. The N-acyl products were found to exist in a dynamic equilibrium of two conformers as suggested by the broad NMR signals. At 26 °C, there may be rotation around the N-C axis of the acylamide function. At the same time, low-temperature NMR measurements at -5 °C revealed the presence of two distinct rotamers that could be characterized by 31P, 13C and 1H NMR data. The modified ß-aminophosphonic derivatives were subjected to a comparative structure-activity analysis on MDA-MB-231, PC-3, A431 and Ebc-1 tumor cell lines, and in a few cases, significant activity was detected.
Assuntos
Antineoplásicos , Organofosfonatos , Organofosfonatos/química , Organofosfonatos/farmacologia , Organofosfonatos/síntese química , Humanos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Aminas/química , Aminas/farmacologia , Aminas/síntese químicaRESUMO
A palladium-catalyzed highly CâS-selective Stille cross-coupling between aryl thianthrenium salts and tri- or tetrasubstituted alkenyl stannanes is described. Herein, critical challenges including site- and chemoselectivity control are well addressed through CâH thianthrenation and CâS alkenylation, thereby providing an expedient access to stereodefined tri- and tetrasubstituted alkenes in a stereoretentive fashion. Indeed, the palladium-catalyzed Stille-alkenylation of poly(pseudo)halogenated arenes displays privileged capability to differentiate CâS over CâI, CâBr, CâCl bonds, as well as oxygen-based triflates (CâOTf), tosylates (CâOTs), carbamates and sulfamates under mild reaction conditions. Sequential and multiple cross-couplings via selective CâX functionalization should be widely applicable for increasing functional molecular complexity. Modular installation of stereospecific alkene motifs into pharmaceuticals illustrated the synthetic application of the present protocol in drug discovery.
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We described a regioselective tri- and tetra-functionalization of the pyridazine scaffold using two readily available building blocks: 3-alkylthio-6-chloropyridazine and 3,4-bis(methylthio)-6-chloropyridazine by performing selective metalations with TMPMgCl â LiCl and catalyst-tuned cross-coupling reactions with arylzinc halides. Several of the resulting pyridazines were converted into more elaborated N-heterocycles such as thieno[2,3-c]pyridazines and 1H-pyrazolo[3,4-c]pyridazines.
RESUMO
A literature survey showed that different derivatives with the 9-phenyl-9H-carbazole or the dihydroindoline scaffold may be of biological activity including cytotoxic effect. Driven by this experience, P-functionalized derivatives of these N-heterocycles were synthesized. Three N-heterocycles, 9-(4-bromophenyl)-9H-carbazole, 3-bromo-9-phenyl-9H-carbazole and 1-(5-bromoindolin-1-yl)ethan-1-one, were coupled with dialkyl phosphites and diarylphosphine oxides using Pd(OAc)2 (10 %) as the catalyst precursor and triethylamine as the base in ethanol under microwave irradiation. The excess of the Y2 P(O)H reagent (Y=alkoxy, aryl) (30 %) served as the P-ligand in its trivalent tautomeric form (Y2 POH), hence there was no need for the usual P-ligands meaning cost and environmental burden. Hence, the presented method is a "green" approach that proved to be more efficient than the preparation by the traditional method. The products, dialkyl phosphonates and tertiary phosphine oxides obtained in 58-84 % yields were characterized, one of them also by single crystal X-ray analysis, and were subjected to inâ vitro biological activity evaluation. A (carbazol)yl-phenylphosphonate, an N-phenyl-(carbazol)yl-phosphonate, a (carbazol)yl-phenylphosphine oxide and an N-phenyl-(carbazol)ylphosphine oxide revealed a significant cytotoxic activity on A549 human non-small-cell lung carcinoma and MonoMac-6 acute monocytic leukemia cancer cells. The cytotoxic effect was significant as compared to that of the reference compounds.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Paládio/química , Micro-Ondas , Catálise , ÓxidosRESUMO
Diethyl α-benzylamino- and α-amino-benzylphosphonates obtained by the Kabachnik-Fields reaction were useful intermediates in the synthesis of other derivatives. Acylation of α-aminophosphonates with acyl chlorides led to the corresponding N-acyl species existing under a dynamic equilibrium of two conformers. Judging from the broad NMR signals, the sterically most crowded N-benzoyl-N-benzyl derivative suffered a hindered rotation around the N-C axis to the acyl carbon atom at 26 °C. Low temperature NMR measurements at -10 °C showed the presence of two distinct rotamers that were characterized. The other acylated α-amino-benzylphosphonates prepared revealed a less hindered rotation. Single crystal X-ray diffraction of the NH-propionyl species showed a dimer, in which the two molecules were held together by rare intermolecular PîOâ¯HN bonds. On the other hand, substituted α-benzylamino-benzylphosphonates prepared by phospha-Mannich reactions were employed, as a new approach, in a second Kabachnik-Fields condensation by reaction with formaldehyde and dialkyl phosphites or secondary phosphine oxides to afford novel N-phosphonoylmethyl- and N-phosphinoylmethyl-α-amino-benzylphosphonates. The structure of the new products was confirmed by two-dimensional NMR spectroscopy. A symmetrical bis derivative was prepared in a diastereoselective manner. A related tris(phosphonoylmethyl)amine species was also synthesized.
RESUMO
A series of complexes [Cu2X2(Pic3PO)2] (X = Cl, Br, I) based on tris(pyridin-2-ylmethyl)phosphine oxide (Pic3PO) has been synthesized. At 298 K, these compounds exhibit thermally activated delayed fluorescence (TADF) of 1(M+X)LCT type with λmax varying from 485 to 545 nm, and quantum efficiency up to 54%. In the TADF process, the halide effect appears as the emission intensification and bathochromic shift of λmax in the following order X = I < Br < Cl. Upon X-ray irradiation, the title compounds emit radioluminescence, the emission bands of which have the same shape as those at TADF, thereby meaning a similar radiative excited state. By contrast to TADF, the halide effect in the radioluminescence is reversed: its intensity grows in the order X = Cl < Br < I, since heavier atoms absorb X-rays more efficiently. These findings essentially contribute to our knowledge about the halide effect in the photo- and radioluminescent Cu(I) halide emitters.
Assuntos
Compostos Inorgânicos , Raios X , Fluorescência , Radiografia , ÓxidosRESUMO
New hydroxy-methylenebisphosphonic derivatives were prepared with different P-functions. The outcome of the reaction of α-oxophosphonates (YC(O)P(O)(OR)2) and dialkyl phosphites or diarylphosphine oxides depended on the Y substituent of the oxo-compound, the nature of the P-reagent and the amount of the diethylamine catalyst. Starting from dimethyl α-oxoethylphosphonate, in the presence of 5% of diethylamine, the corresponding Pudovik adduct was the single product. While using 40% of the catalyst, the rearranged species with the >P(O)-O-CH-P(O)< skeleton was the exclusive component. A similar reaction of α-oxobenzylphosphonate followed the rearrangement protocol. X-ray crystallography revealed not only the spatial structures of the three products, but also an intricate pattern evolving from the interplay of slight chemical differences, solvent inclusion and disorder as well as H-bridge patterns, which invite further investigation. In vitro activity of the compounds was assessed on different tumor cell cultures using end-point-type cell tetrazolium-based measurements. These structure-activity studies revealed a cytostatic effect for four rearranged derivatives containing aromatic units. One of them had a pronounced effect on MDA-MB 231 and Ebc-1 cells, showing IC50 = 37.8 and 25.9 µM, respectively.
Assuntos
Compostos Radiofarmacêuticos , Raios X , Radiografia , Sais de Tetrazólio , DietilaminasRESUMO
DFT-calculations allow prediction of the reactivity of uncommon N-heterocyclic scaffolds of pyrazolo[1,5-a]pyrimidines and imidazo[1,2-b]pyridazines and considerably facilitate their functionalization. The derivatization of these N-heterocycles was realized using Grignard reagents for nucleophilic additions to 5-chloropyrazolo[1,5-a]pyrimidines and TMP2 Zn â 2 MgCl2 â 2 LiCl allowed regioselective zincations. In the case of 6-chloroimidazo[1,2-b]pyridazine, bases such as TMP2 Zn â MgCl2 â 2 LiCl, in the presence or absence of BF3 â OEt2 , led to regioselective metalations at positions 3 or 8. Subsequent functionalizations were achieved with TMPMgCl â LiCl, producing various polysubstituted derivatives (up to penta-substitution). X-ray analysis confirmed the regioselectivity for key functional heterocycles.
Assuntos
Magnésio , Zinco , Indicadores e Reagentes , PirimidinasRESUMO
The growing reservations against the use of any kind of chlorine source in pyrotechnic items revolutionize the predominantly empirical development of strobe formulations in two ways. First, a conventionally applied ammonium perchlorate oxidizer needs to be replaced. Second, visible light emissions should no longer be generated by metastable monochloride species. Moreover, until now, toxic substances such as potassium dichromate have been added in order to achieve a more pronounced strobe effect. This work evaluates the potential of stearic acid-treated ceric ammonium nitrate to serve as an oxidizing agent in next-generation strobe compositions. For this purpose, its microscopic structure, energetic properties, and stability under ambient conditions were assessed. A two-component mixture with a magnesium-aluminum alloy was investigated, which should allow for the introduction of copper-based colorants. This potentially paves the way for the first environmentally friendly blue strobe formulations.
RESUMO
We report a lateral sodiation of alkyl(hetero)arenes using on-demand generated hexane-soluble (2-ethylhexyl)sodium (1) in the presence of TMEDA. (2-Ethylhexyl)sodium (1) is prepared via a sodium packed-bed reactor and used for metalations at ambient temperature in batch as well as in continuous flow. The resulting benzylic sodium species are subsequently trapped with various electrophiles including carbonyl compounds, epoxides, oxetane, allyl/benzyl chlorides, alkyl halides and alkyl tosylates. Wurtz-type couplings with secondary alkyl halides and tosylates proceed under complete inversion of stereochemistry. Furthermore, the utility of this lateral sodiation is demonstrated in the synthesis of pharmaceutical relevant compounds. Thus, fingolimod is prepared from p-xylene applying the lateral sodiation twice. In addition, 7-fold isotopically labeled salmeterol-d7 and fenpiprane as well as precursors to super linear alkylbenzene (SLAB) surfactants are prepared.
Assuntos
Compostos de Epóxi , Sódio , Catálise , Íons , Preparações FarmacêuticasRESUMO
We report a new convenient preparation of dicarbamoylzincs of type (R1 R2 NCO)2 Zn by the treatment of ZnCl2 and formamides R1 R2 NCHO with LiTMP in THF (15 °C, 15â min) or by the reaction of formamides R1 R2 NCHO with TMP2 Zn (25 °C, 16â h). This second method tolerates sensitive groups such as an ester, ketone or nitro function. Reaction of these dicarbamoylzincs with allylic, benzylic, aryl, alkenyl bromides, acid chlorides, aldehydes or enones provided various polyfunctional amides in 47-97 % yields. 13 C NMR characterization of these new carbamoylzinc derivatives is reported.
Assuntos
Amidas , Compostos Organometálicos , Aldeídos/química , Amidas/química , Formamidas , Cetonas , Compostos Organometálicos/químicaRESUMO
In the field of energetic binders, only hydroxy-terminated glycidyl azide polymer (GAP) has found widespread application and prevailed in the market. However, oxiranes such as glycidyl azide (GA) allow two ring-opening modes during polymerization and thus lead to polymers of different termination causing inhomogeneous curing results. An elegant solution is the polymerization of 3-azidooxetane as only terminating primary hydroxyl groups are formed. Beyond this, poly(3-azidooxetane) and GAP are equal in other aspects due to the similar repetition unit. Since literature methods for the preparation of 3-azidooxetane either employed toxic solvents, gave low yields or impurified product, or could not be reproduced, a new synthesis method was developed to afford pure material and satisfying yields. The syntheses of toluene- and methanesulfonic acid esters of oxetan-3-ol as precursors were also significantly improved in comparison to the literature and their molecular structures elucidated by single-crystal X-ray diffraction. The aforementioned compounds and poly(3-azidooxetane) were intensively studied by vibrational and multinuclear NMR spectroscopy (1H, 13C, 14N), differential scanning calorimetry, and elemental analysis. The key compound, 3-azidooxetane, was compared to glycidyl azide regarding performance using the EXPLO5 V6.04 thermochemical code and their sensitivity toward external stimuli like shock and friction assessed according to BAM standard procedures.
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Fluoromethyl-2,4,6-trinitrophenylsulfonate has been prepared for the first time and qualified as a simple to use monofluoromethylating reagent. Its molecular structure in the solid state has been determined by single-crystal X-ray diffraction studies. This reagent proves to be effective for the electrophilic introduction of a CH2F group into selected chalcogen and nitrogen nucleophiles. Monofluoromethyl derivatives of various bifunctional N,O-nucleophiles have been synthesized using fluoromethyl-2,4,6-trinitrophenylsulfonate. Due to the good crystallizing properties of the anion, the fluoromethylated products as well as side products that are difficult to identify by nuclear magnetic resonance spectroscopy can readily be characterized by X-ray crystallographic techniques.
RESUMO
Aryl- and heteroaryl-dichlorophosphines are mildly and selectively made in a one-pot synthesis in moderate to good yields starting from the respective aryl bromides or five-membered heterocycles, following lithiation with nBuLi, transmetalation with ZnCl2, and subsequently the reaction with PCl3. Selected aryl- and heteroaryl-dichlorophosphines were successfully synthesized using this reaction method and could easily be purified after isolation. The intermediate formation of the organozinc species is essential, as it prevents the formation of multiple substitution products. Important are also the reaction conditions: the usage of the proper solvent for the respective aromatic precursors and removal of the remaining salts by addition of a dioxane/pentane mixture. Depending on the solvent and steric demand of the substituent, mono- and bis-substitution products can be formed but formation also prevented. Hereby, different organozinc species might play an important role.
Assuntos
Brometos , Indicadores e ReagentesRESUMO
The syntheses of a sterically demanding, multidentate bis(quinaldinyl)phenylphosphine oxide ligand and some Cu(I) and Ag(I) complexes thereof are described. By introducing a methylene group between the quinoline unit and phosphorus, the phosphine oxide ligand gains additional flexibility. This specific ligand design induces not only a versatile coordination chemistry but also a rarely observed and investigated behavior in solution. The flexibility of the birdlike ligand offers the unexpected opportunity of open-wing and closed-wing coordination to the metal. In fact, the determined crystal structures of these complexes show both orientations. Investigations of the ligand in solution show a strong dependency of the chemical shift of the CH2 protons on the solvent used. Variable-temperature, multinuclear NMR spectroscopy was carried out, and an interesting dynamic behavior of the complexes is observed. Due to the introduced flexibility, the quinaldinyl substituents change their arrangements from open-wing to closed-wing upon cooling, while still staying coordinated to the metal. This change in conformation is completely reversible when warming up the sample. Based on 2D NMR spectra measured at -80 °C, an assignment of the signals corresponding to the different arrangements was possible. Additionally, the copper(I) complex shows reversible redox activity in solution. The combination of structural flexibility of a multidentate ligand and the positive redox properties of the resulting complexes comprises key factors for a possible application of such compounds in transition-metal catalysis. Via a reorganization of the ligand, occurring transition states could be stabilized, and selectivity might be enhanced.
RESUMO
A set of rhenium-catalyzed arylation-acyl cyclizations between (hetero)arylmagnesium halides and enol lactones through a cascade C(sp2 )-C(sp2 )/C(sp2 )-C(sp2 ) bond formation under mild reaction conditions has been developed. Indeed, a wide range of functional groups on both organomagnesium halides and enol lactones is well tolerated by the simple rhenium catalysis, thus furnishing polyfunctionalized indenones in one-pot fashion and with complete control of the regioselectivity. Moreover, this approach also provides a straightforward synthetic route to neolignan and (iso)pauciflorolâ F. Mechanistic studies demonstrated that the reaction involves a sequence of syn-carborhenation and intramolecular nucleophilic addition.
RESUMO
The sodiation of substituted acrylonitriles and alkenyl sulfides in a continuous flow set-up using NaDA (sodium diisopropylamide) in EtNMe2 or NaTMP (sodium 2,2,6,6-tetramethylpiperidide)â TMEDA in n-hexane provides sodiated acrylonitriles and alkenyl sulfides, which are subsequently trapped in batch with various electrophiles such as aldehydes, ketones, disulfides and allylic bromides affording functionalized acrylonitriles and alkenyl sulfides. This flow-procedure was successfully extended to other acrylates by using Barbier-type conditions.
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Chiral ß-aminoalkylzinc halides were prepared starting from optically pure commercial ß-amino-alcohols. These amino-alcohols were converted to the corresponding N-pyrrolyl-protected alkyl iodides which undergo a zinc insertion in the presence of LiCl (THF, 25 °C, 10-90â min). Subsequent Negishi cross-coupling or acylation reactions with acid chlorides produced amino-derivatives with retention of chirality. Diastereoselective CBS-reductions of some prepared N-pyrrolyl-ketones provided 1,3-subsituted N-pyrrolyl-alcohols with high diastereoselectivity. Additionally, a deprotection procedure involving an ozonolysis allowed the conversion of the pyrrole-ring into a formamide without loss of optical purity.
RESUMO
We report the formation and characterization of two diastereomeric thiol-ene addition products of the asthma medication Montelukast within chewing tablets. Widespread tin-based thermal stabilizers dioctyltin bis(2-ethylhexyl thioglycolate) and monooctyltin tris(2-ethylhexyl thioglycolate), used in the manufacturing process of the medication's forming foil, were identified as the source of the thiol reactant, showing that these stabilizers may play a part in the degradation of Montelukast and APIs with functionalities similar to those of Montelukast, which should be considered during development of medication. The isolation and analysis of these impurities was performed by HPLC and UV-vis spectroscopy. HRMS and NMR data were collected to characterize and determine the structures of these compounds.