Synthesis Of Organic Molecules Research Articles

Recent Routes in Synthesis and Biological Activity of Pyrimido[4,5-b] Quinoline Derivatives: A Review (Part II)

The synthesis of organic molecules has been a tremendous and rapid advance in the recent decade to obtain high biological and pharmacological activities. In this review, the organic synthesis of pyrimido[4,5-b]quinoline derivatives is considered an alternative method to traditional procedures for treating many diseases that affect humans. Also, by transferring electrons, stereoselective syntheses occur via organic reactions in various unnatural and natural conditions at room temperature and normal pressure. We found that the structure of pyrimido[4,5-b]quinoline derivatives was formed by substrates, bases, electrophiles, and low-level and highly stable reagents that can be broadly applied to synthesize more heterocycles. These reagents include: 2- nitrobenzaldehyde; 3-(benzyloxy)-4-methoxy-2-nitrobenzaldehyde; 4,5-dimethoxy-2- nitrobenzaldehyde; 2-aminobenzaldehyde; 2-aminoquinoline-3-carboxamide; 2-chloroquinoline3-carbaldehyde; 2-bromobenzaldehyde; 2-chloroquinoline-3-carbonitrile; 2-chloroquinoline-3- carboxylic acid; aniline; phenyl-methanamine; amino-quinoline-3-carboxylic acid /aminoquinoline-carbonitrile; amino-6,7-dimethoxy-quinoline-3-carbonitrile; amino-oxolo [4,5- g]quinolin-carboxamide; 3-(aminomethyl) quinolin-2-amine; 4-aminobenzo[d][1,3] dioxole-5- carbaldehyde; thiourea; ethyl 3-oxo-butanoate; 2-cyano-acetamide; 2-(bis (methylthio) methylene) malononitrile; ethyl 3,3-diamino-2-cyanoacrylate; naphthalene-1,4-dione; and N-carbamoyl-2- cyanoacetamide derivatives. The prepared pyrimido[4,5-b]quinoline derivatives were described through means of the following chemical reactivity: alkylation, bromination, chlorination, cyclocondensation, cyclization, acylation, oxidation-reduction, dehydration, addition reaction and Vilsmeier-Haack reaction (Vilsmeier reagent).

Protocellular Heme and Iron-Sulfur Clusters.

ConspectusCentral to the quest of understanding the emergence of life is to uncover the role of metals, particularly iron, in shaping prebiotic chemistry. Iron, as the most abundant of the accessible transition metals on the prebiotic Earth, played a pivotal role in early biochemical processes and continues to be indispensable to modern biology. Here, we discuss our recent contributions to probing the plausibility of prebiotic complexes with iron, including heme and iron-sulfur clusters, in mediating chemistry beneficial to a protocell. Laboratory experiments and spectroscopic findings suggest plausible pathways, often facilitated by UV light, for the synthesis of heme and iron-sulfur clusters. Once formed, heme displays catalytic, peroxidase-like activity when complexed with amphiphiles. This activity could have been beneficial in two ways. First, heme could have catalytically removed a molecule (H2O2) that could have had degradative effects on a protocell. Second, heme could have helped in the synthesis of the building blocks of life by coupling the reduction of H2O2 with the oxidation of organic substrates. The necessity of amphiphiles to avoid the formation of inactive complexes of heme is telling, as the modern-day electron transport chain possesses heme embedded within a lipid membrane. Conversely, prebiotic iron-sulfur peptides have yet to be reported to partition into lipid membranes, nor have simple iron-sulfur peptides been found to be capable of participating in the synthesis of organic molecules. Instead, iron-sulfur peptides span a wide range of reduction potentials complementary to the reduction potentials of hemes. The reduction potential of iron-sulfur peptides can be tuned by the type of iron-sulfur cluster formed, e.g., [2Fe-2S] versus [4Fe-4S], or by the substitution of ligands to the metal center. Since iron-sulfur clusters easily form upon stochastic encounters between iron ions, hydrosulfide, and small organic molecules possessing a thiolate, including peptides, the likelihood of soluble iron-sulfur clusters seems to be high. What remains challenging to determine is if iron-sulfur peptides participated in early prebiotic chemistry or were recruited later when protocellular membranes evolved that were compatible with the exploitation of electron transfer for the storage of energy as a proton gradient. This problem mirrors in some ways the difficulty in deciphering the origins of metabolism as a whole. Chemistry that resembles some facets of extant metabolism must have transpired on the prebiotic Earth, but there are few clues as to how and when such chemistry was harnessed to support a (proto)cell. Ultimately, unraveling the roles of hemes and iron-sulfur clusters in prebiotic chemistry promises to deepen our understanding of the origins of life on Earth and aids the search for life elsewhere in the universe.

Path toward "Net Zero Organic Synthesis".

Researchers over the past ∼200 years have accomplished the synthesis of simple to very complex molecules; however, the concept of ideal synthesis has still not reached maturity. Of late, the "Net Zero" concept has captured the imagination of many fields of technology, in tune with Ideal Synthesis. The current Viewpoint covers the principles of ideal synthesis being discussed in the literature and how one could take up the synthesis of organic molecules considering the Net Zero concept to make this central science well-accepted by critics of this important field.

Mechanochemical Synthesis of Stimuli Responsive Microgels

AbstractMechanochemical approaches are widely used for the efficient, solvent‐free synthesis of organic molecules, however their applicability to the synthesis of functional polymers has remained underexplored. Herein, we demonstrate for the first time that mechanochemically triggered free‐radical polymerization allows solvent‐ and initiator‐free syntheses of structurally and morphologically well‐defined complex functional macromolecular architectures, namely stimuliresponsive microgels. The developed mechanochemical polymerization approach is applicable to a variety of monomers and allows synthesizing microgels with tunable chemical structure, variable size, controlled number of crosslinks and reactive functional end‐groups.

Modern Strategies for Carbon Isotope Exchange

AbstractIn contrast to stable and natural abundant carbon‐12, the synthesis of organic molecules with carbon (radio)isotopes must be conceived and optimized in order to navigate through the hurdles of radiochemical requirements, such as high costs of the starting materials, harsh conditions and radioactive waste generation. In addition, it must initiate from the small cohort of available C‐labeled building blocks. For long time, multi‐step approaches have represented the sole available patterns. On the other side, the development of chemical reactions based on the reversible cleavage of C−C bonds might offer new opportunities and reshape retrosynthetic analysis in radiosynthesis. This review aims to provide a short survey on the recently emerged carbon isotope exchange technologies that provide effective opportunity for late‐stage labeling. At present, such strategies have relied on the use of primary and easily accessible radiolabeled C1‐building blocks, such as carbon dioxide, carbon monoxide and cyanides, while the activation principles have been based on thermal, photocatalytic, metal‐catalyzed and biocatalytic processes.

Modern Strategies for Carbon Isotope Exchange.

In contrast to stable and natural abundant carbon-12, the synthesis of organic molecules with carbon (radio)isotopes must be conceived and optimized in order to navigate through the hurdles of radiochemical requirements, such as high costs of the starting materials, harsh conditions and radioactive waste generation. In addition, it must initiate from the small cohort of available C-labeled building blocks. For long time, multi-step approaches have represented the sole available patterns. On the other side, the development of chemical reactions based on the reversible cleavage of C-C bonds might offer new opportunities and reshape retrosynthetic analysis in radiosynthesis. This review aims to provide a short survey on the recently emerged carbon isotope exchange (CIE) technologies that provide effective opportunity for late-stage labeling. At present, such strategies have relied on the use of primary and easily accessible radiolabeled C1-building blocks, such as carbon dioxide, carbon monoxide and cyanides, while the activation principles have been based on thermal, photocatalytic, metal-catalyzed and biocatalytic processes.

Monte Carlo simulation of sugar synthesis on icy dust particles intermittently irradiated by UV in a protoplanetary disk

Context. While synthesis of organic molecules in molecular clouds or protoplanetary disks is complex, observations of interstellar grains, analyses of carbonaceous chondrites, and UV photochemistry experiments are rapidly developing and are providing constraints on and clues to the complex organic molecule synthesis in space. This motivates us to construct a theoretical synthesis model. Aims. We developed a new code to simulate global reaction sequences of organic molecules and apply it to sugar synthesis by intermittent UV irradiation on the surface of icy particles in a protoplanetary disk. Here we show the first results of our new simulation. Methods. We applied a Monte Carlo method to select reaction sequences from all possible reactions, using the graph-theoretic matrix model for chemical reactions and modeling reactions on the icy particles during UV irradiation. Results. We obtain results consistent with the organic molecules in carbonaceous chondrites and obtained by experiments, albeit through a different pathway from the conventional formose reactions previously suggested. During UV irradiation, loosely bonded O-rich large molecules are continuously created and destroyed. After UV irradiation is turned off, the ribose abundance rapidly increases through the decomposition of the large molecules via breakage of O−O bonds and replacements of C−OH by C−H to reach O/C = 1 for sugars. The sugar abundance is regulated mostly by the total atomic ratio H/O of starting materials, but not by their specific molecular forms. Deoxyribose is simultaneously synthesized, and most of the molecules end up in complexes with C-rich molecules.

Catalytic applications of graphene oxide towards the synthesis of bioactive scaffolds through the formation of carbon–carbon and carbon–heteroatom bonds

Abstract During the past several decades, metal-based catalysis is one of the major and direct approaches for the synthesis of organic molecules. Nowadays, materials containing predominantly carbon element which are termed as carbocatalysts, become the most promising area of research to replace transition metal catalysts. In this context of carbocatalysis, the use of graphene oxide (GO) and GO-based materials are under spotlight due to their sustainability, environmental benignity and large scale-availability. The presence of oxygen containing functional groups in GO makes it benign oxidant and slightly acidic catalyst. This chapter provides a broad discussion on graphene oxide (GO) as well as its preparation, properties and vast area of application. The catalytic activity of GO has been explored in different organic transformations and it has been recognized as an oxidation catalyst for various organic reactions.

Catalytic Enantioselective Diels Alder Reaction: Application in the Synthesis of Antiviral Agents

The Diels–Alder reaction (DAR) is one of the most effective and reliable strategies for the construction of six-membered carbocyclic and heterocyclic rings, and it is widely used in the synthesis of organic molecules and drugs. Due to the high regio- and stereo-selectivity and its versatility, DARs have represented a powerful tool for organic chemistry for many years. In addition, the asymmetric DAR has become a fundamental synthetic approach in the preparation of optically active six-membered rings and natural compounds. The COVID-19-related pandemic requires continuous research; DAR represents an useful method to obtain optically active intermediates for the synthesis of antiviral agents under different catalytic conditions. We would like to highlight an intriguing synthetic procedure applied to the development of novel synthetic protocols that are potentially useful against a large panel of viruses and other unmet diseases.

Synthetic Approaches to Complex Organic Molecules in the Cold Interstellar Medium

The observation and synthesis of organic molecules in interstellar space is one of the most exciting and rapidly growing topics in astrochemistry. Spectroscopic observations especially with millimeter and submillimeter waves have resulted in the detection of more than 250 molecules in the interstellar clouds from which stars and planets are ultimately formed. In this review, we focus on the diverse suggestions made to explain the formation of Complex Organic Molecules (COMs) in the low-temperature interstellar medium. The dominant mechanisms at such low temperatures are still a matter of dispute, with both gas-phase and granular processes, occurring on and in ice mantles, thought to play a role. Granular mechanisms include both diffusive and nondiffusive processes. A granular explanation is strengthened by experiments at 10 K that indicate that the synthesis of large molecules on granular ice mantles under space-like conditions is exceedingly efficient, with and without external radiation. In addition, the bombardment of carbon-containing ice mantles in the laboratory by cosmic rays, which are mainly high-energy protons, can lead to organic species even at low temperatures. For processes on dust grains to be competitive at low temperatures, however, non-thermal desorption mechanisms must be invoked to explain why the organic molecules are detected in the gas phase. Although much remains to be learned, a better understanding of low-temperature organic syntheses in space will add both to our understanding of unusual chemical processes and the role of molecules in stellar evolution.

Sustainable and Reusable Sulfonic Acid-Functionalized Task-Specific Ionic Liquid Catalysts for Multicomponent Reactions. A Review

Improvements in Sustainable Organic Synthesis are usually related to the investigation of less hazardous, non-corrosive and renewable materials, as well as waste prevention, energy efficiency, solvent-free reactions, and the development of efficient reusable catalysts. In this context, multicomponent reactions emerged as important strategies for the rapid and more sustainable synthesis of organic molecules. In addition, the use of task-specific ionic liquids as non-conventional solvents and/or catalysts in multicomponent reactions has recently received great attention, contributing to the development of greener synthetic methodologies. This review describes the studies on the use of structurally diverse homogeneous and heterogeneous sulfonic acid-functionalized task-specific ionic liquids as acidic catalysts for multicomponent reactions applied to the synthesis of nitrogen- and oxygen-based heterocycles, as well as related compounds. The combination of the green credentials of multicomponent reactions and acidic ionic liquids are able to improve process sustainability and green metrics, contributing to sustainable chemical development and, ultimately, to economic growth and cleaner industrial production.

Unusual Chemical Processes in Interstellar Chemistry: Past and Present

The chemistry that occurs in interstellar clouds consists of both gas-phase processes and reactions on the surfaces of dust grains, the latter particularly on and in water-dominated ice mantles in cold clouds. Some of these processes, especially at low temperature, are very unusual by terrestrial standards. For example, in the gas-phase, two-body association reactions form a metastable species known as a complex, which is then stabilized by the emission of radiation under low-density conditions, especially at low temperatures. In the solid phase, it has been thought that the major process for surface reactions is diffusive in nature, occurring when two species undergoing random walks collide with each other on a surface that has both potential wells and intermediate barriers. There is experimental evidence for this process, although very few rates at low interstellar temperatures are well measured. Moreover, since dust particles are discrete, modeling has to take account that reactant pairs are on the same grain, a problem that can be treated using stochastic approaches. In addition, it has been shown more recently that surface reactions can occur more rapidly if they undergo any of a number of non-diffusive processes including so-called three-body mechanisms. There is some experimental support for this hypothesis. These and other unusual gaseous and solid-state processes will be discussed from the theoretical and experimental points of view, and their possible role in the synthesis of organic molecules in interstellar clouds explained. In addition, their historical development will be reviewed.

Light harnessing by Algae: from fundamental investigations to light-based biotechnologies

Light is the most abundant source of energy on earth and is used by photosynthetic organisms to drive the synthesis of organic molecules. Light also allows the catalysis of few enzymes, the photoenzymes. Among them, the fatty acid photodecarboxylase (FAP) isolated from microalgae converts fatty acids into hydrocarbons. We present here our understanding of the role of hydrocarbons produced by FAP in vivo, the catalytic mechanism of the FAP and its potential biotechnological applications.

Novel D-π-A phenothiazine and dibenzofuran organic dyes with simple structures for efficient dye-sensitized solar cells

Synthesis of organic molecules is imperative for users to gain a low-cost sensitizer for the purpose of dye-sensitized solar cells (DSSCs). Phenothiazine and Dibenzofuran based organic dyes ((5-(10H-phenothiazin-2-yl) thiophene-2-carbaldehyde and (Z)-2-cyano-N'-((5-(dibenzo[b,d]furan-4-yl)thiophen-2-yl)methylene) acetohydrazide)) are synthesized and optimized as sensitizers for DSSC applications. The synthetic dye compounds are characterized by Mass, FT-IR, NMR and absorption spectra. The molecular energy levels of the PTCH and BFCH were determined using cyclic voltammetry to assess the driving forces for electron injection, redox behavior and regeneration of the dye. The experimental spectral frequencies of the dye molecules are compared to the calculated results. Furthermore, its electronic and photovoltaic properties have been evaluated using Time Dependent-Density Functional Theory (TD-DFT) method. Effects of the acceptor unit (cyanoacetohydrazide), π-conjugation bridges, phenothiazine and dibenzofuran (Donor) were studied. Quantum chemical parameters have also been analyzed using density functional theory. In addition, an important analysis of the reorganization energy, molecular electrostatic potential and the natural bond orbital had also been studied for the title molecules.

Time and Pot Economy in Total Synthesis.

We would all like to make or obtain the materials or products we want as soon as possible. This is human nature. This is true also for chemists in the synthesis of organic molecules. All chemists would like to make their target molecules as soon as possible, particularly when their interest is in the physical or biological properties of those molecules.As demonstrated by today's COVID-19 (SARS-CoV-2) pandemic, rapid synthesis is also crucial to enable chemists to deliver effective therapeutic agents to the community. Several concepts are currently well-accepted as important for achieving this: atom economy, step economy, and redox economy. Considering the importance of synthesizing organic molecules rapidly, I recently proposed adding the concept of time economy.In a multisep synthesis, each step has to be completed within a short period of time to make the desired molecule rapidly. The development of rapid reactions is important but also insufficient. After each step, frequent and repetitive workup operations such as quenching the reaction, extraction, separation of water and organic phases, drying the organic phase, filtration, evaporation, and purification may be required, and the time necessary for these processing operations must be taken into account. Indeed, some of the most time-consuming operations in most syntheses are the purification stages.On the other hand, one-pot reactions are processes in which several sequential reactions are conducted in a single reaction vessel, which avoids the need to purify intermediates. One-pot reactions are a useful way to shorten the total synthesis time, and the approach generally leads to an increase in the yield and a reduction in the amount of chemical waste formed. Thus, I also propose the importance of pot economy.On the basis of these concepts of time and pot economy, we have accomplished efficient syntheses of several natural products and medicines. The key to the success of these syntheses is the use of diphenylprolinol silyl ether as an effective catalyst in a one-pot reaction, in which it does not disturb the subsequent reactions. Our strategy is (1) to construct the chiral key skeletons and/or key components of natural products and medicines directly using organocatalyst-mediated one-pot reactions and (2) to conduct the subsequent transformations to the final molecules in a small number of pots utilizing the internal quench method. By means of this strategy, PGE1 methyl ester, estradiol methyl ether, and clinprost were synthesized in three, five, and seven pots, respectively. Furthermore, (-)-oseltamivir, ABT-341, baclofen, and Corey lactone were synthesized in a single reaction vessel. Further optimization of the reactions in terms of time economy allowed (-)-oseltamivir and Corey lactone to be synthesized within 60 and 152 min, respectively. These syntheses will be highlighted as case studies. Although the organocatalyst is a key compound in this Account, pot- and time-economical syntheses can be expanded to organometallic chemistry and, indeed, to organic chemistry in general.

Urea-Assisted Synthesis and Characterization of Saponite with Different Octahedral (Mg, Zn, Ni, Co) and Tetrahedral Metals (Al, Ga, B), a Review.

Clay minerals surfaces potentially play a role in prebiotic synthesis through adsorption of organic monomers that give rise to highly concentrated systems; facilitate condensation and polymerization reactions, protection of early biomolecules from hydrolysis and photolysis, and surface-templating for specific adsorption and synthesis of organic molecules. This review presents processes of clay formation using saponite as a model clay mineral, since it has been shown to catalyze organic reactions, is easy to synthesize in large and pure form, and has tunable properties. In particular, a method involving urea is presented as a reasonable analog of natural processes. The method involves a two-step process: (1) formation of the precursor aluminosilicate gel and (2) hydrolysis of a divalent metal (Mg, Ni, Co, and Zn) by the slow release of ammonia from urea decomposition. The aluminosilicate gels in the first step forms a 4-fold-coordinated Al3+ similar to what is found in nature such as in volcanic glass. The use of urea, a compound figuring in many prebiotic model reactions, circumvents the formation of undesirable brucite, Mg(OH)2, in the final product, by slowly releasing ammonia thereby controlling the hydrolysis of magnesium. In addition, the substitution of B and Ga for Si and Al in saponite is also described. The saponite products from this urea-assisted synthesis were tested as catalysts for several organic reactions, including Friedel–Crafts alkylation, cracking, and isomerization reactions.

Metal Nanoparticles: An Efficient Tool for Heterocycles Synthesis and Their Functionalization via C-H Activation

Background: Metal nanoparticles have been extensively used in the synthesis of organic molecules during the last few decades especially due to their high catalytic activity. Organic reactions involving C-H functionalisations are very much in demand as they provide a direct method of derivatisation of organic molecules, thus making the process economical. In the recent years, metal nanoparticles catalysed C-H activation reactions have led to the design of useful molecules especially heterocyclic motifs which form the core structure of drugs and thus have high biological and industrial importance. Methods: In this review, we present a collection of reactions where metal nanoparticles are instrumental in the synthesis and functionalization of heterocycles via C-H activation. The review consists of three units namely, Nano-copper catalysed C-H activation reactions, nano-palladium catalysed CH activation reactions and other nano-metals catalysed C-H activation reactions. Results: The discussion reflects the scope of nano-metals as effective catalysts for the synthesis and functionalization of heterocycles as well as the efficiency of nano-metals towards catalysing economic and environmentally viable reaction protocols. Conclusion: The theme of this review is to correlate nanometal catalysis, heterocyclic synthesis and C-H activation, each of which in itself forms an integral part of modern day chemical research. Thus, the review will hopefully highlight the need for future development and research in this area and be instrumental in guiding researchers towards fulfilling that goal.

Zinc Battery Driven by an Electro-Organic Reactor Cathode

Synthesis of organic molecules by utilizing the principles of electrochemistry satisfies 9 out of the 12 postulates of green chemistry, conferring electrochemical synthetic methodologies with clean, safe, and green tags. However, electro-organic synthesis is a heterogeneous interfacial reaction demanding significant driving force in terms of voltage or current. Here, we demonstrate an unusual route for electro-organic synthesis during electricity generation in a battery, where the positive half-cell is designed to function as an organic reactor generating useful chemicals and fuel molecules. The proposed electro-organic synthesizer Zn battery couples organic synthesis with power production during discharge chemistry, thereby demonstrating its tremendous potential in the sustainable energy landscape.

Olefination of Alkyl Halides with Aldehydes by Merging Visible-Light Photoredox Catalysis and Organophosphorus Chemistry

SummaryCarbon-carbon double bond (C=C) formation is a crucial transformation in organic chemistry. Visible-light photoredox catalysis provides economical and sustainable opportunities for the development of novel and peculiar organic reactions. Here we report a method for the olefination of alkyl halides with aldehydes by visible-light photoredox catalysis using triphenylphosphine as a reductive quencher (103 examples). This transformation accommodates a variety of aldehydes including paraformaldehyde; aqueous formaldehyde; 2,2,2-trifluoroacetaldehyde monohydrate; 2,2,2-trifluoro-1-methoxyethanol; and other common aldehydes. The present method exhibits several advantages, including operational simplicity, mild reaction conditions, wide functional group tolerance, and amenability to gram-scale synthesis. We anticipate that it will be widely used in the synthesis of organic molecules, natural products, biological molecules, and polymers.

Covalent Organic Frameworks-Organic Chemistry Beyond the Molecule.

The synthesis of organic molecules has at its core, purity, definitiveness of structure, and the ability to access specific atoms through chemical reactions. When considering extended organic structures, covalent organic frameworks (COFs) stand out as a true extension of molecular organic chemistry to the solid state, because these three fundamental attributes of molecular organic chemistry are preserved. The fact that COFs are porous provides confined space within which molecules can be further modified and controlled.