Non-traditional pathways of extraterrestrial formation of organic compounds

The mechanisms of solid-phase reactions that have been experimentally and theoretically studied during recent decades and can be directly related to the formation of organic substances in space and their delivery to Earth and to the problems of prebiotic evolution are considered. Among these mechanisms are molecular tunneling (hypothesis of the cold prehistory of life), polycondensation of solid monomers by shock waves (problem of the delivery of organic substances to Earth by meteorites), thermal and thermal-wave explosions. and oscillations of temperature and radical concentrations in small cold particles under radiation exposure, mechanochemical explosions and autowave propagation of chemical reactions due to the positive feedback between fragile destruction of solids and reactions at freshly formed surfaces. Written on the basis of the report at the International Conference “Chemical Physics at the Threshold of XXI Century,” April 16–19, 1996, Moscow. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 409–417, March, 1997.     

Continuous‐Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

In the past few years, continuous‐flow reactors with channel dimensions in the micro‐ or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of this type, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, microreactor technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. This Review discusses recent literature examples of continuous‐flow organic synthesis where hazardous reactions or extreme process windows have been employed, with a focus on applications of relevance to the preparation of pharmaceuticals.     

Recent advances in solventless organic reactions: towards benign synthesis with remarkable versatility

A paradigm shift away from using solvents in organic synthesis as solventless reactions can lead to improved outcomes, and more benign synthetic procedures, in for example aldol condensation reactions, sequential aldol and Michael addition reactions en route to Kr?hnke type pyridines, reactions leading to 3-carboxycoumarins, benzylidenes, 4-aryl-1,4-dihydropyridines and 2-aryl-1,2,3,4-tetrahydroquinazolines, and oligomerisation reactions for the synthesis of cavitands; kinetic considerations for the reaction of two solids can only be explained if a eutectic melt is formed during the reaction.     

Autowave modes of polymerization and other reactions in solid frozen matrixes near of absolute zero and their role in mechanisms of fast chemical transformations of substance in universe

Almost two decades ago there were discovered new autowave selfpropagation phenomena in the cryo‐chemical reactions at investigating of chemical solid phase transformations near absolute zero of temperatures. Such an autowave regime is observed for different classes of chemical reactions (polymerisation, copolymerisation and also hydrocarbon halogenation, hydro‐halogenation etc). The chemical transformations studied at the such low temperatures 4–77 K proceeded with so great rates that they can be compared only with the fastest high‐temperature combustion reactions known in chemistry. It allows to advance a principally new autowave conception of the matter chemical activity in solid state. The essentially non‐Arrenius conception is based on the assumption that a mechanical energy accumulated in solid matrix can be transformated to the chemical forms.     

Plasmonic heterogeneous catalysis for organic transformations

Plasmonic catalysis has been recognised as a promising alternative to many conventional thermal catalytic processes in organic synthesis. In addition to their high activity in fine chemical synthesis, plasmonic photocatalysts are also able to maintain control of selectivity under mild conditions by utilising visible-light as an energy source. This review provides an overview of the recent advances in organic transformations with plasmonic metal nanostructures, including selective reduction, selective oxidation, cross-coupling and addition reactions. We also summarize the photocatalysts and catalytic mechanisms involving surface plasmon resonance. Finally, control of reaction pathway and strategies for tailoring product selectivity in fine chemical synthesis are discussed.     

Using geminal dicationic ionic liquids as solvents for high-temperature organic reactions

[reaction: see text] Several organic reactions conducted at high temperatures, including the isomerization reaction, the Claisen rearrangement, and the Diels-Alder reaction, were investigated in three geminal dicationic ionic liquids with high thermal stability. High to moderate yields of the products for most entries were obtained. Advantages of these approaches are discussed. These ionic liquids were shown to be recyclable. The utility of these ionic liquid solvents for high-temperature organic reactions was demonstrated.     

Modular Microreaction Systems for Homogeneously and Heterogeneously Catalyzed Chemical Synthesis

Until now, microreaction devices designed for a specific type of reaction were used mainly for highly exothermic, very fast reactions. Described is a modular microreaction system and its application to representative homogeneous and heterogeneous reactions important in organic synthesis. The modular microreaction system allows continuous flow processes to be optimized and employed effectively in the chemical laboratory. The modular microreaction systems proved also versatile for syntheses requiring moderate reaction times, thus extending their application to a large fraction of organic reactions. The use of the modular and cleanable microreaction systems to rapidly develop optimized reaction conditions provides an excellent basis for the development of many chemical transformations scalable from milligram to ton production quantities.     

Dinitrogen extrusion from diazene in organic synthesis

Radical-mediated reactions have many advantages in the construction of complex molecular scaffolds by forging chemical bonds of high challenge. Diazenes, including 1,1-diazenes and 1,2-diazenes, can generate biradical species via nitrogen extrusion under thermal or photochemical conditions. The superior reactivity of the generated biradical enables various types of synthetic transformations with excellent chemoselectivity and has been applied to the complex natural products synthesis. In this mini-review, the modes of reaction are summarized and discussed, namely ring contraction via nitrogen deletion, homo or hetero-dimerization, trimethylenemethane (TMM)-diyl cycloaddition. Applications of these classes of reactions in complex natural product synthesis are illustrated. Last but not least, the current state, future directions, and opportunities for dinitrogen extrusion reaction from diazenes are highlighted and discussed.     

Thermal transformation of solid organic compounds

The thermal decomposition of malonic acid was investigated with a derivatograph. Values of activation energy, frequency factor and reaction order were determined from thermal decomposition curves employing different calculation methods. Equations derived for the calculation of kinetic data of inorganic thermal reactions were also found to be suitable in the case of organic reactions. Convenient methods were developed for the calculation of the activation energy, using the DTG curve.     

Identificaiton of potential thermal runaways using small scale thermal analytical techniques

With industry's focus on the early identification of potential thermal runaways in chemical processes, it is important that these potential thermal hazards be identified early in a process' development. Thermal runaways can be initiated in several ways: through an uncontrolled heat of reaction, the initiation of an exothermic decomposition/oxidation, or a combination of these two. It is therefore critical that information on exothermic decomposition/oxidation and heat of reaction be easily obtainable using small scale laboratory reactions.A small scale thermal hazards identification program, using process samples from a 200 ml reaction and small scale thermal analytical techniques, identifies potential thermal runaways rapidly. The small scale thermal hazards identification program utilizes three small scale thermal analytical techniques developed at the Merck Research Laboratories. These include the use of specially designed DSC reusable metal crucibles to identify closed system exothermic activity in process samples, the Small Scale Isothermal Age Technique to accurately determine exothermic onset temperatures and Syringe Injection calorimetry to determine heat of reactions which occur at room temperature.     

A differential thermal analysis (dta) and thermogravimetric analysis (tga) study of some organic acids. part II

The differential thermal analysis and thermogravimetric analysis curves of l6 organic acids are presented. The “procedural weight-loss temperatures” for the anhydrous acids ranged from 115° for salicylhydroxamic acid to 250° for 5-aminosalicylic acid. The DTA curves were characterized by endothermic and exothermic peaks which were caused by fusion, vaporization, sublimation, and decomposition reactions.     

Microwaves in organic synthesis. Thermal and non-thermal microwave effects

Microwave irradiation has been successfully applied in organic chemistry. Spectacular accelerations, higher yields under milder reaction conditions and higher product purities have all been reported. Indeed, a number of authors have described success in reactions that do not occur by conventional heating and even modifications of selectivity (chemo-, regio- and stereoselectivity). The effect of microwave irradiation in organic synthesis is a combination of thermal effects, arising from the heating rate, superheating or "hot spots" and the selective absorption of radiation by polar substances. Such phenomena are not usually accessible by classical heating and the existence of non-thermal effects of highly polarizing radiation--the "specific microwave effect"--is still a controversial topic. An overview of the thermal effects and the current state of non-thermal microwave effects is presented in this critical review along with a view on how these phenomena can be effectively used in organic synthesis.     

铟试剂在有机合成中的应用

综述了近十年来铟试剂在有机合成中的应用。重点讨论了铟试剂参与的有关碳-碳键形成的反应,如羰基化合物的烯丙基化、Reformatsky反应、成环以及三氯化铟作为Lewis酸的催化反应以及铟试剂的水相反应化学。铟试剂的这些反应,尤其是水相反应具有其它金属有机试剂在化学选择性和立体选择性方面具有独特的优势。     

Synthesis of Densely Packaged,Ultrasmall Pt02 Clusters within a Thioether‐Functionalized MOF: Catalytic Activity in Industrial Reactions at Low Temperature

The gram‐scale synthesis, stabilization, and characterization of well‐defined ultrasmall subnanometric catalytic clusters on solids is a challenge. The chemical synthesis and X‐ray snapshots of Pt⁰₂ clusters, homogenously distributed and densely packaged within the channels of a metal–organic framework, is presented. This hybrid material catalyzes efficiently, and even more importantly from an economic and environmental viewpoint, at low temperature (25 to 140 °C), energetically costly industrial reactions in the gas phase such as HCN production, CO₂ methanation, and alkene hydrogenations. These results open the way for the design of precisely defined catalytically active ultrasmall metal clusters in solids for technically easier, cheaper, and dramatically less‐dangerous industrial reactions.     

Synthesis of Densely Packaged,Ultrasmall Pt02 Clusters within a Thioether‐Functionalized MOF: Catalytic Activity in Industrial Reactions at Low Temperature

The gram‐scale synthesis, stabilization, and characterization of well‐defined ultrasmall subnanometric catalytic clusters on solids is a challenge. The chemical synthesis and X‐ray snapshots of Pt⁰₂ clusters, homogenously distributed and densely packaged within the channels of a metal–organic framework, is presented. This hybrid material catalyzes efficiently, and even more importantly from an economic and environmental viewpoint, at low temperature (25 to 140 °C), energetically costly industrial reactions in the gas phase such as HCN production, CO₂ methanation, and alkene hydrogenations. These results open the way for the design of precisely defined catalytically active ultrasmall metal clusters in solids for technically easier, cheaper, and dramatically less‐dangerous industrial reactions.     

Thermal analysis of the pyrolytic behaviors of a highly crosslinked polymer

Thermogravimetric-mass spectrometric (TG/MS) and differential scanning calorimetric (DSC) techniques were used in the characterization of oxidative and nonoxidative degradation reactions of a highly crosslinked divinylbenzene/styrene copolymer. When the copolymer was subjected to a temperature-programmed air environment, four exothermic reactions were detected. The initial small exothermic reaction, starting at ca. 125°C and reaching its maximum at ca. 180°C, was presumed to result from the decomposition of peroxides. The second exothermic reaction, which overlapped with the initial one and peaked at ca. 270°C, was attributed to oxidation with a significant amount of oxygen uptake and liberation of some gaseous products such as CO₂, styrene, benzaldehyde, ethylstyrene, and ethylbenzaldehyde. The strongest exothermic reaction took place at ca. 290–380°C and had its peak at ca. 360°C. Associated with this reaction was the generation of many gaseous pyrolysates, as given above. The exothermic reaction continued at a relatively constant rate from ca. 380°C to the maximum temperature of the experiment (500°C) with the release of only one gaseous product (CO₂). The initial exothermic reaction can be eliminated by controlled thermal decomposition of peroxides; therefore, a more thermally stable polymer can be obtained. Exothermic reactions, starting at ca. 170°C, were observed. Pyrolytic reactions in an inert gas were also studied.     

Epoxide Opening versus Silica Condensation during Sol–Gel Hybrid Biomaterial Synthesis

Hybrid organic–inorganic solids represent an important class of engineering materials, usually prepared by sol–gel processes by cross‐reaction between organic and inorganic precursors. The choice of the two components and control of the reaction conditions (especially pH value) allow the synthesis of hybrid materials with novel properties and functionalities. 3‐Glycidoxypropyltrimethoxysilane (GPTMS) is one of the most commonly used organic silanes for hybrid‐material fabrication. Herein, the reactivity of GPTMS in water at different pH values (pH 2–11) was deeply investigated for the first time by solution‐state multinuclear NMR spectroscopic and mass spectrometric analysis. The extent of the different and competing reactions that take place as a function of the pH value was elucidated. The NMR spectroscopic and mass spectrometric data clearly indicate that the pH value determines the kinetics of epoxide hydrolysis versus silicon condensation. Under slighly acidic conditions, the epoxy‐ring hydrolysis is kinetically more favourable than the formation of the silica network. In contrast, under basic conditions, silicon condensation is the main reaction that takes place. Full characterisation of the formed intermediates was carried out by using NMR spectroscopic and mass spectrometric analysis. These results indicate that strict control of the pH values allows tuning of the reactivity of the organic and inorganic moities, thus laying the foundations for the design and synthesis of sol–gel hybrid biomaterials with tuneable properties.     

Functionalization of Metal–Organic Frameworks through the Postsynthetic Transformation of Olefin Side Groups

For the first time, the adaptability of the C?C double bond as a versatile precursor for the postsynthetic modification (PSM) of microporous materials was extensively investigated and evaluated. Therefore, an olefin‐tagged 4,4′‐bipyridine linker was synthesized and successfully introduced as pillar linker within a 9,10‐triptycenedicarboxylate (TDC) zinc paddle‐wheel metal–organic framework (MOF) through microwave‐assisted synthesis. Different reactions, predominately used in organic chemistry, were tested, leading to the development of new postsynthetic reactions for the functionalization of solid materials. The postsynthetic oxidation of the olefin side groups applying osmium tetroxide (OsO₄) as a catalyst led to the formation of a microporous material with free vicinal diol functionalities. The epoxidation with dimethyldioxirane (DMDO) enabled the synthesis of epoxy‐functionalized MOFs. In addition to that, reaction procedures for a postsynthetic hydroboration with borane dimethyl sulfide as well as a photoinduced thiol–ene click reaction with ethyl mercaptan were developed. For all of these PSMs, yields of more than 90 % were obtained, entirely maintaining the crystallinity of the MOFs. Since the direct introduction of the corresponding groups by means of pre‐synthetic approaches is hardly possible, these new PSMs are useful tools for the functionalization of porous solids towards applications such as selective adsorption, separation, and catalysis.     

Water-based biphasic media for exothermic reactions: green chemistry strategy for the large scale preparation of clofibric acid and analogues

A water-based biphasic reaction process has been developed for conducting exothermic reactions without organic solvents. This procedure is rapid, simple, and suitable for small scale synthesis as well as larger (multi-molar) scale reactions. The preparation of several hundred grams of clofibric acid and analogues by this eco-friendly and energy-efficient procedure is described. Smaller amounts of these compounds were prepared by the friction-activated ‘Grindstone Chemistry’ method described previously.     

Application of organic selenides and tellurides in organic synthesis

This paper describes the progress on the synthesis of organic selenides and tellurides and their application in organic synthesis.Low valent selenium and telluronium compounds having high reducing selectivity can be used to form carbon-hydrogen bonds as special reducing reagents.Telluronium ylides can react with aldehydes and ketones by Wittig-type condensation to produce (E)-configuration alkenes stereoselectively.α-Phenylselanyl arsonium ylides were prepared by transyl-idation reaction of arsonium ylides with phenylselanyl halides which can undergo Wittig-type reactions with carbonyl compounds to give (Z)-α-selanyl-α,β-unsaturated compounds with high stereoselectiv-ity.Zirconium,tin,boron,halogen,metal or hetero-atom were introduced in organoselenium and telluronium compounds as new difunctional group reagents.Under transition metal catalysis,the corresponding cross coupling reactions provide new methods of formation of carbon-carbon double bonds,which were used in the stereoselective synthesis of