Organic Chemistry Research Research Articles

ChemInform Abstract: Transition Metal‐Catalyzed Decarboxylative Coupling Reactions of Alkynyl Carboxylic Acids

AbstractReview: 68 refs.

John Cymerman Craig

John C Craig, an Emeritus Professor of Chemistry and Pharmaceutical Chemistry at the University of California, San Francisco, died suddenly on 26 September of complications related to cardiac disease. John was 92 years old and still maintained an office at the School of Pharmacy at UCSF. His final research was a series of six papers with colleagues at the London School of Tropical Medicine to find out ‘just how the antimalarials kill the parasites inside the human red blood cells.' John's career began at the University of London where he received Bachelor of Science degrees in both Physics and Chemistry (with first class Honors) followed by a PhD in Organic Chemistry from Imperial College, London. From 1942 to 45 John was a Gas Identification Officer and instructed both military and civilians in Chemical Defense, for which he was awarded the Defense Medal. John taught at London University's Charing Cross Hospital in Organic Chemistry, was Senior Lecturer in Organic Chemistry at the University of Sydney (St Paul's College) from 1948 to 1961, and also received the D.Sc. degree from Sydney University in 1962, for his research in Organic and Medicinal Chemistry. In 1958 he became Visiting Scientist at The National Institutes of Health and Walter Reed Army Medical Center for research in anti-radiation drugs. John began his 30-year career at UCSF in 1960, teaching both at the undergraduate and graduate level. He was Professor of Chemistry from 1963 to 1971, Department of Pharmaceutical Chemistry Chairman from 1963 to 71, and Associate Dean of Research from 1971 to 1992. He was selected by the UCSF Academic Senate as the Annual UCSF Faculty Research Lecturer in 1974, and received the first Academic Senate UCSF Service Award in 1993. His research produced over 250 publications in Organic and Medicinal Chemistry and focused on chemical structure and biological activity, including work on the synthesis of vitamin A, chemotherapy of tuberculosis and malaria, and development of stable isotope tracer technology for diagnostic tests for genetic diseases in infants and newborns (to replace the use of radioactive tracers). John was awarded the Research Award in Natural Products from the American Pharmaceutical Association Foundation in 1967, and the Research Achievement Award in Pharmaceutical Analysis from the American Pharmaceutical Scientists in 1988. He was elected to Fellowship in the Academy of Pharmaceutical Scientist in 1967 and to membership in the American College of Neuropsychopharmacology in 1975. For the past 21 years John was a member of the UCSF board of the Faculty Emeriti Association and served as Vice chairman, Chairman and Historian of the state-wide Council of UC Emeriti. John was active in amateur radio from the age of 14 years. In San Francisco he was a member of the SF Radio Club and the Cathay Radio Club. He participated in the UCSF Emergency Network. Since finding a rare early English cookery book (the earliest cookery books were full of medicinal cures) on a barrow in London as a student, John was busy collecting antiquarian English cookery books. In 1988 the Bancroft Library, University California Berkeley presented 100 volumes of John's collection in an exhibit titled ‘Four Hundred Years of English Diet and Cookery: 1541–1939'. He was a member of the Bancroft Council, Bancroft Library, 1989–1997, and edited ‘The Cookery Manuscript of Lillie Hitchcock Coit, 1870–1890, San Francisco' which the Bancroft published in 1998. He is survived by his wife Elaine of San Francisco, his daughter, Elizabeth (Eric) and grandchildren Benjamin and Katherine of Park City, Utah; his son, Anthony (Ruth) of Dorset, UK, and grandsons Thomas (Kelly) of Perth, Australia, and Matthew (Ruth) of Devon, UK, and four great grandchildren.

Proton Fingerprints Portray Molecular Structures: Enhanced Description of the1H NMR Spectra of Small Molecules

The characteristic signals observed in NMR spectra encode essential information on the structure of small molecules. However, extracting all of this information from complex signal patterns is not trivial. This report demonstrates how computer-aided spectral analysis enables the complete interpretation of 1D (1)H NMR data. The effectiveness of this approach is illustrated with a set of organic molecules, for which replicas of their (1)H NMR spectra were generated. The potential impact of this methodology on organic chemistry research is discussed.

RECENT ADVANCES OF QUINAZOLINONE DERIVATIVES AS MARKER FOR VARIOUS BIOLOGICAL ACTIVITIES

Heterocyclic chemistry comprises at least half of all organic chemistry research worldwide. Quinazolinone and its derivative s constitute an important class of heterocyclic compounds. The chemistry of quinazoline compounds has more than centuries old history; however the intense searc h for biologically active substances in this series began only in the last few decades. In this present communication an attempt is made to cover the medicinally active compounds, along with the recent discoveries, which were reported to posses various biological activities.

4th Young Investigator Workshop

The present issue of Chemical Monthly is dedicated to the work of young researchers participating in the 4th Young Investigator Workshop (YIW) which took place in August 2012 at Vienna University of Technology (http://investi gator.ias.tuwien.ac.at/). This novel symposium series was launched in 2009 by the Organic Division of the European Association for Chemical and Molecular Sciences (EuChEMS) as a meeting of the most promising researchers in Europe at the beginning of their independent career. Participants are nominated by the chemical societies of their respective countries, initially solely from EuChEMS member states. The series gained recognition rapidly among young researchers due to the unique setup: young scientists are free to network among themselves in an informal environment, sharing their most recent breakthrough results. These unique experiences made YIW become a regular event within the Organic Division of EuChEMS. Due to the success of past workshops, executives within the division decided to open up the meeting beyond European borders. For the first time, young researchers from Asia and North and South America joined a handpicked selection of aspiring young team leaders from Europe, making YIW4Vienna the largest meeting in this series to date. A total of 38 delegates from 23 countries celebrated a firework display of organic chemistry during several hot days in mid-summer in Vienna. It was this substantially increased audience together with the extremely high scientific quality of the presentations which resulted in a significantly increased visibility of this event. Ultimately, the attention of Springer was stirred to support the event as major sponsor and prompted this publisher to dedicate a special issue of this journal to the next generation of researchers in organic chemistry. We are sure you will enjoy reading this issue covering some of the exciting research presented at the workshop from many different areas of organic chemistry. You should also memorize the names of the corresponding authors of the articles, since they will be amongst the researchers leaving significant footprints within the field in the forthcoming years.

Transition metal-catalyzed decarboxylative coupling reactions of alkynyl carboxylic acids

The decarboxylative coupling of alkynyl carboxylic acids is an attractive area of research in organic chemistry, because the structure of aryl alkyne is one of the important building blocks for the synthesis of p-conjugated compounds. The use of alkynyl carboxylic acid as an alkyne source has several advantages in handling and storage. As a catalyst, palladium, copper, nickel, and silver were employed in the decarboxylative coupling reactions. The formation of C–C (sp2–sp, sp–sp and sp3–sp), C–N, C–P and C–S bonds has been developed. This review aims to illustrate the development of the decarboxylative coupling reaction of alkynyl carboxylic acids.

Hydroxamic Acids in Asymmetric Synthesis

Metal-catalyzed stereoselective reactions are a central theme in organic chemistry research. In these reactions, the stereoselection is achieved predominantly by introducing chiral ligands at the metal catalyst's center. For decades, researchers have sought better chiral ligands for asymmetric catalysis and have made great progress. Nevertheless, to achieve optimal stereoselectivity and to catalyze new reactions, new chiral ligands are needed. Because of their high metal affinity, hydroxamic acids play major roles across a broad spectrum of fields from biochemistry to metal extraction. Dr. K. Barry Sharpless first revealed their potential as chiral ligands for asymmetric synthesis in 1977: He published the chiral vanadium-hydroxamic-acid-catalyzed, enantioselective epoxidation of allylic alcohols before his discovery of Sharpless asymmetric epoxidation, which uses the titanium-tartrate complex as the chiral reagent. However, researchers have reported few highly enantioselective reactions using metal-hydroxamic acid as catalysts since then. This Account summarizes our research on metal-catalyzed asymmetric epoxidation using hydroxamic acids as chiral ligands. We designed and synthesized a series of new hydroxamic acids, most notably the C2-symmetric bis-hydroxamic acid (BHA) family. V-BHA-catalyzed epoxidation of allylic and homoallylic alcohols achieved higher activity and stereoselectivity than Sharpless asymmetric epoxidation in many cases. Changing the metal species led to a series of unprecedented asymmetric epoxidation reactions, such as (i) single olefins and sulfides with Mo-BHA, (ii) homoallylic and bishomoallylic alcohols with Zr- and Hf-BHA, and (iii) N-alkenyl sulfonamides and N-sulfonyl imines with Hf-BHA. These reactions produce uniquely functionalized chiral epoxides with good yields and enantioselectivities.

Homogeneous and heterogeneous catalysts for multicomponent reactions

Organic synthesis performed through multicomponent reactions is an attractive area of research in organic chemistry. Multicomponent reactions involve more than two starting reagents that couple in an exclusive ordered mode under the same reaction conditions to form a single product which contains the essential parts of the starting materials. Multicomponent reactions are powerful tools in modern drug discovery processes, because they are an important source of molecular diversity, allowing rapid, automated and high throughput generation of organic compounds. This review aims to illustrate progress in a large variety of catalyzed multicomponent reactions performed with acid, base and metal heterogeneous and homogeneous catalysts. Within each type of multicomponent approach, relevant products that can be obtained and their interest for industrial applications are presented.

Problem types in synthetic organic chemistry research: Implications for the development of curricular problems for second-year level organic chemistry instruction

Understanding of the nature of science is key to the development of new curricular materials that mirror the practice of science. Three problem types (project level, synthetic planning, and day-to-day) in synthetic organic chemistry emerged during a thematic content analysis of the research experiences of eight practising synthetic organic chemists. Project-level problems include the overarching purpose of synthesizing target molecules. Synthetic planning problems include both the retrosynthetic analysis of target molecules and subsequent development of synthetic pathway proposals. Day-to-day problems include the ‘hurdles’ faced in research laboratories while attempting to realize proposed synthetic pathways. Recommendations are made as to how understanding of the three problem types impact undergraduate-level organic chemistry instruction.

DC-electrochemiluminescence (ECL with a coreactant)—principle and applications in organic chemistry

This review is focused on the so-called DC-electrochemiluminescence (or ECL with coreactant), its fundamentals and use in basic research in organic and coordination chemistry, photo(electro)chemistry and photophysics, where ECL is not still fully explored. This review is also meant to remind the fellow scientists to the substantial contribution of Prof. Fritz Pragst to this field. An appropriate attention is given to the following two types of research problems where ECL plays a crucial role: (1) selective generation of triplet states enabling investigation of their reactions and estimation of their energies; (2) Use of DC-ECL for mechanistic studies in organic electrochemistry, for interception of short-living intermediates and for visualization of electrode processes. The main aim of this paper is not to rewrite already existing reviews in another form, but to complete the whole picture of ECL research and to remind the reader to several fundamental studies, ideas, and papers hoping that they could be inspirative for organic and molecular electrochemists.

Vitomir Šunjić and Michael J. Parnham: Signposts to chiral drugs: organic synthesis in action

This relatively slim volume will be of interest to those working in synthetic organic chemistry, particularly in the medicinal chemistry area, and having as their aim the discovery of new drug entities for the pharmaceutical industries. It is co-written by an academic (VS), having considerable experience of teaching and research in synthetic organic chemistry allied to medicinal chemistry, and a pharmacologist (MJP) who has extensive experience of research and development involving a variety of therapeutic agents (including anti-inflammatory drugs) in an industrial context. In an introductory chapter, the authors present an overview of the challenges facing organic synthesis in the search for new drug entities and point out the importance of chiral synthesis in the design of molecules able to bind to three dimensional biological target sites, recognising that almost 70% of the top 200 marketed drugs are optically pure. The remainder of the book provides 15 self-contained chapters, each focusing on a specific chiral drug structure, describing its therapeutic profile in terms of its biological target and then presenting a detailed discussion of synthetic approaches to the molecule, the creation of chiral sites and chiral separation techniques. In some cases, retrosynthetic pathways are discussed in relation to potential synthetic strategies and the use of modern reagents, homogeneous catalytic processes and the all-important scaling-up considerations, are highlighted. The range of examples chosen covers a very wide range of therapeutic areas, including anti-inflammatory and anticancer drugs, hypertension and blood lipid control, the treatment of type 2 diabetes, HIV-1, depression and anxiety, antibacterial and anti-asthmatic agents, anti-histamines and even the common household aid (-)-Menthol. Also included is a chapter on 3-amino-1,4benzodiazepines and their potential in the treatment of Alzheimer’s disease. At the end of the book, there is also a useful summary of synthetic methods and concepts that are developed in the individual chapters, together with a useful index. The standard of presentation is very high, with many clearly presented reaction schemes, and each chapter has a comprehensive list of references to the specific area.

Vitomir Šunjić and Michael J. Parnham, “Signposts to chiral drugs: organic synthesis in action”

This relatively slim volume will be of interest to those working in synthetic organic chemistry, particularly in the medicinal chemistry area, and having as their aim the discovery of new drug entities for the pharmaceutical industries. It is co-written by an academic (VS), having considerable experience of teaching and research in synthetic organic chemistry allied to medicinal chemistry, and a pharmacologist (MJP) who has extensive experience of research and development involving a variety of therapeutic agents (including anti-inflammatory drugs) in an industrial context. In an introductory chapter, the authors present an overview of the challenges facing organic synthesis in the search for new drug entities and point out the importance of chiral synthesis in the design of molecules able to bind to three dimensional biological target sites, recognising that almost 70% of the top 200 marketed drugs are optically pure. The remainder of the book provides 15 self-contained chapters, each focusing on a specific chiral drug structure, describing its therapeutic profile in terms of its biological target and then presenting a detailed discussion of synthetic approaches to the molecule, the creation of chiral sites and chiral separation techniques. In some cases, retrosynthetic pathways are discussed in relation to potential synthetic strategies and the use of modern reagents, homogeneous catalytic processes and the all-important scaling-up considerations, are highlighted. The range of examples chosen covers a very wide range of therapeutic areas, including anti-inflammatory and anticancer drugs, hypertension and blood lipid control, the treatment of type 2 diabetes, HIV-1, depression and anxiety, antibacterial and anti-asthmatic agents, anti-histamines and even the common household aid (-)-Menthol. Also included is a chapter on 3-amino-1,4benzodiazepines and their potential in the treatment of Alzheimer’s disease. At the end of the book, there is also a useful summary of synthetic methods and concepts that are developed in the individual chapters, together with a useful index. The standard of presentation is very high, with many clearly presented reaction schemes, and each chapter has a comprehensive list of references to the specific area.

GC-MS and spectrophotometric analysis of biodegradation of new disazo dye by Trametes versicolor

In this study; sub-tropical white rot fungi, Trametes versicolor was investigated for its ability to degrade 4-(3'-methyl-4'-(4"-nitrophenyl)azo- 1'H-pyrazol-5'-ylazo)-3-methyl- H-pyrazol-5-on in the mediums containing glucose and different concentrations of degrade dye in batch systems. This dye was synthetized at Pamukkale Universtiy of Organic Chemistry research laboratory. Samples were collected on 10 days, and was detected by Shimadzu UV-1600A spectrophotometry. Decolorization study showed that this disazo dye was removed by more than 70% in 10 days. Laccase enzyme activity was detected in samples and then last sample was analyzed by GC-MS. Metabolites weren't showed in GC-MS result. It was concluded that T. versicolor could achieve the biodegradation of this new disazo dye.

ChemInform Abstract: Synthesis of Amines by the Electrophilic Amination of Organomagnesium, ‐Zinc, ‐Copper, and ‐Lithium Reagents

AbstractReview: 151 refs.

Microwave-Assisted Solvent-Dependent Reaction: Chemoselective Synthesis of Quinoxalin-2(1H)-ones, Benzo[d]imidazoles and Dipeptides

A microwave-assisted solvent-dependent chemoselective reaction dealing with 4-arylidene-2-phenyloxazol-5-ones and diverse ortho-diamines to achieve three types of molecular scaffolds, 3-benzylquinoxalin-2(1H)-ones, benzimidazole and β-amino dipeptides is reported. The procedures feature short reaction time, good to excellent yields, operational simplicity, as well as easily available starting materials. These compounds are of importance for organic chemistry and medicinal chemistry research.

ChemInform Abstract: Catalytic Asymmetric Allylic Alkylation Employing Heteroatom Nucleophiles: A Powerful Method for C—X Bond Formation

AbstractReview: 142 refs.

Synthesis of amines by the electrophilic amination of organomagnesium, -zinc, -copper, and -lithium reagents

Amines are important building blocks in the synthesis of various important organic compounds such as pharmaceuticals, agrochemicals, polymers, dyes, xerographic and photographic materials. Therefore, development of new synthetic methods for amines has attracted the attention of many researchers. Among modern amination methods, electrophilic amination of an easily available organometallic reagent has been found to be a viable alternative method and continues to be an active area for research in synthetic organic chemistry. To date various type of aminating reagents have been used in the electrophilic amination of organomagnesium, -zinc, -copper, and -lithium reagents for the introduction of free or protected amino moieties, such as haloamines, substituted hydroxylamines, imines, oxaziridines, oximes, diazonium salts, azodicarboxylates, azides, and metal amides. This review covers the literature published in the last twenty years in detail. In addition, older literature has been mentioned briefly.

New progress in aggregation-induced emission research

The most fascinating aspect of scientific research is the constant deciphering of mysterious puzzles and the continuous transformation of our mode of thinking. While textbook knowledge is the foundation of human wisdom, some traditional concepts can later prove to be imperfect or even incorrect owing to limitations of the observations and understanding of the involved natural phenomena in particular periods of history. The once popular “geocentric theory”, for example, was totally wrong and hampered scientists’ exploration of the universe, and the “vitality of the doctrine” badly hindered advancement in organic chemistry research. Innovations are needed to break the restraints of such traditional concepts. The area of organic solids research focuses on investigations of molecular functional materials with peculiar optical, electronic and magnetic properties. In this area, a generally accepted concept is that chromophore aggregation always leads to luminescence quenching. This phenomenon of aggregation-caused quenching (ACQ) is termed the “concentration-quenching effect” in the textbook Molecular Fluorescence. Researchers are working on the development of organic light-emitting diodes (OLEDs), in which luminescent molecules are used as a solid film, one of the aggregation forms. Scientists have tried hard to suppress the aggregate formation of luminescent molecules through different approaches, with the aim of mitigating the ACQ effect and achieving OLEDs with high efficiencies. In 2001, Tang’s group discovered a phenomenon exactly opposite to the ACQ effect. The researchers found that luminogen aggregation played a constructive, instead of destructive, role in the light-emitting process; a series of silole molecules, such as hexaphenylsilole (HPS) and methylpentaphenylsilole (MPPS; Figure 1), were found to be nonluminescent in the solution state but emissive in the aggregated state with luminescent quantum yields three orders of

A Reactivity-Driven Approach to the Discovery and Development of Gold-Catalyzed Organic Reactions.

Approaches to research in organic chemistry are as numerous as the reactions they describe. In this account, we describe our reactivity-based approach. Using our work in the area of gold-catalysis as a background, we discuss how a focus on reaction mechanism and reactivity paradigms can lead to the rapid discovery of new synthetic tools.

Catalytic asymmetric allylic alkylation employing heteroatom nucleophiles: a powerful method for C–X bond formation

Metal catalyzed asymmetric allylic alkylation (AAA) reactions have been an extensively studied and fruitful area of research in organic chemistry. The use of heteroatom-centered nucleophiles in this reaction is a powerful method for asymmetric C–X (X = heteroatom) bond formation. This perspective summarizes developments and applications of metal catalyzed AAA reactions employing heteroatom nucleophiles.