Field Of Heterocyclic Chemistry Research Articles

Urea-Promoted Neat Synthesis of Fused Dihydroisoquinolines and Disubstituted Pyridines: A Mechanistic Observation with Molecular-Sensing Studies.

An efficient and short synthesis of fused dihydroisoquinolines, diaryl substituted pyridine derivatives in good to high yields has been established by using an environmentally safe, solvent-metal-oxidant-free tandem approach. In this article, we discuss how the electrocyclic reaction is more pronounced in the solid phase in the presence of urea, whereas the typical aza-Michael addition is more prominent in presence of arylamine in the solution phase for 3-(2-formylcycloalkenyl)acrylic ester derivative substrates. The wide range of substrates and urea-promoted neat synthesis made our approach more significant in medical and also analytical science. Moreover, an isoquinoline alkaloid decumbenine B analogue has been synthesized by using our newly developed neat methodology. We have also investigated the photophysical properties of the synthesized fused dihydroisoquinoline derivatives. One of the synthesized molecules was used as a sensor for the selective detection of toxic picric acid. Therefore, the effective neat synthesis and molecular sensing applications of these compounds made our approach more exciting in the field of heterocyclic chemistry.

Total Synthesis of Altemicidin: A Surprise Ending for a Monoterpene Alkaloid.

Monoterpene alkaloids encompass distinct chemical diversity and wide-ranging bioactivity. Their compact complexity has made them popular as synthetic targets and has inspired many distinct strategies and tactics in the field of heterocyclic chemistry. This article documents the evolution of a synthetic program aimed at accessing the unusual sulfonamide-containing natural product altemicidin, which was generally believed to be a monoterpene alkaloid throughout our entire synthetic investigations but has recently been found to originate through an unexpected and quite disparate biosynthetic pathway. By leveraging a pyridine dearomatization/cycloaddition strategy, we developed a concise pathway to the 5,6-fused bicyclic azaindane core and, after significant experimentation, an ultimate synthesis of altemicidin itself. Tactics to productively manipulate the multiple functional groups present on this highly polar scaffold proved challenging but were eventually realized via several carefully orchestrated and chemoselective transformations-investments that paid dividends in the form of significantly shorter chemical synthesis. Surprisingly, the bond-forming logic between our presumed abiotic synthetic strategy to this alkaloid class and its subsequently identified biosynthetic pathway is eerily similar.

Evaluation of the anti-inflammatory, analgesic, anti-pyretic and anti-ulcerogenic potentials of synthetic indole derivatives

A large number of new synthetic compounds are synthesized in the field of heterocyclic chemistry having a variety of biological potentials. In the present study, some synthetic indole derivatives are used to check anti-inflammatory, analgesic, antipyretic and gastroprotective activity in albino mice. Albino mice of either sex of reproductive age were used for each study (n = 5). In anti-inflammatory activity, the negative control (NC) and positive control group animals were treated with normal saline and 10 mg/kg of indomethacin respectively. The treated groups received the twenty four different synthetic chemicals, after 30 min of sub cutaneous injection of carrageenan. In analgesic activity, hot-plate method is used and for each group the latency period was recorded at zero moment of the provision of required dose and after 30, 60, 90, 120 and 180 min. In anti-pyretic activity, Pyrexia was induced by using Brewer's yeast method. Before any treatment and then after duration of 18 h, the rectal temperatures were recorded. Among all the chemicals, only those chemicals which show any potential related to above mentioned activities were selected for gastroprotective activity. The gastroprotective activity was performed to check the gastric ulcers by using 300 mg/kg of single oral dose of indomethacin to animals of all groups except NC group. This study helped to screen out the most potent indole derivatives 3a-II and 4a-II from the 24 synthetic indole derivatives which demonstrated the best biological potential (anti-inflammatory, analgesic, antipyretic, and gastroprotection) as compared to the remaining ones. The micrometric and biochemical results also support the histological findings. Out of the twenty-four novel indole amines tested, 3a-II and 4a-II have shown the effective pharmacological capacity and additionally have not shown any overt and systemic toxicity. Thus these two indole amines need further in-depth pharmacokinetic and pharmacodynamics studies before they are recommended for any pre-clinical trial.

Apatite phosphate doped by cobalt as hight efficient catalyst of multi-component synthesis of therapeutic spiropyrimidine compound

Spiropyrimidines vanquish a significant situation in the field of heterocyclic chemistry, they are broadly utilized as an antibacterial, an inhibitor of multidrug opposition, or an antiplatelet and antithrombotic drug. Phosphate, the principal Moroccan mineral wealth occupies a vital spot in the economic sector and its valuation is a goal continually looked for. Among the conceivable outcomes of valorization, its utilization in heterogeneous catalysis which thought about an exceptionally encouraging new way. In this context, the focus on the reaction of the synthesis of spiropyrimidine, catalyzed by natural phosphate (NP) and by fluoroapatite (Fap), are used alone or doped by cobalt. These phosphate catalysts were characterized by XRD, IR and SEM, while the synthesized spiropyrimidine was identified by IR, GC–MS and NMR. The obtained yield with fluorapatite doped by cobalt (Co/Fap), at room temperature in ethanol is very high and shows a high impact performance induced by a synergistic effect compared to that of NP alone.Graphical

A Review of Ruthenium-catalyzed C-N Bond Formation Reactions for the Synthesis of Five-membered N-heterocycles

The field of heterocyclic chemistry has been revolutionized using transition metal catalysts in recent years. Various research groups have focused on the development of general protocols to achieve better functional group compatibilities and greater levels of molecular complexity under mild reaction conditions, using easily available starting substrates. The methodologies used earlier for their synthesis were less approachable to organic chemists because of their high cost, highly specified instrumentation and inconvenient methods. For both stereoselective and regioselective synthesis of five-membered nitrogen- containing heterocycles, cyclic reactions that are Ru-catalyzed have known to be very efficient. These methods have many advantages as compared to alternative pathways involved in the synthesis of heterocyclic compounds. In this review article, we concentrated on the synthesis of nitrogen-containing five-membered heterocycles in the presence of a ruthenium catalyst. This review mostly covers the literature published during the period from 1977-2019.

Isothiazoles in the Design and Synthesis of Biologically Active Substances and Ligands for Metal Complexes

The chemistry of isothiazoles is being intensively developed, which is evidenced by the wide range of selective transformations involving the isothiazole heterocycle and the high biological activity of its derivatives that can be used as effective new drugs and plant protection chemicals. Some representatives of isothiazoles have proven to be synergists of bioactive substances, which opens the way to lower the doses of drugs used and is especially important in cancer chemotherapy. In the framework of the present review, the accomplishments in the chemistry of isothiazoles over the past 18 years are examined, whilst current strategies for the synthesis of isothiazole-containing molecules and key directions of studies in this field of heterocyclic chemistry are discussed. Considerable attention is paid to chlorinated isothiazoles and strategies for their use in the synthesis of biologically active substances. In addition, a comprehensive review of existing literature in the field of metal complexes of isothiazoles is given, including the results and prospects for the practical use of isothiazole–metal complexes as catalysts for cross-coupling reactions in aqueous and aqueous–alcoholic media (‘green chemistry’).1 Introduction2 Synthesis by Ring-Forming Reactions2.1 Intramolecular Cyclization2.2 (4+1)-Heterocyclization2.3 (3+2)-Heterocyclization2.4 Syntheses by Ring Transformations3 Isothiazoles by Ring Functionalization Reactions: Nucleophilic Substitution, Cross-Coupling and Side-Chain Functionalization4 Selected Syntheses of Biologically Active Isothiazole Derivatives5 Isothiazoles in the Synthesis of Transition-Metal Complexes and in Metal-Complex Catalysis6 Conclusion

A Review of 2,3-Benzodiazepine-related Compounds: Diazepines and 1,2,5- Triazepines Fused with Five-membered Nitrogen Heterocycles

Background: 2,3-Benzodiazepines represent an important class of biologically active compounds, some members of this family have reached the human clinical stage. With formal bioisosteric replacement of the benzene ring to five-membered nitrogen heterocycles, several new diazepine and 1,2,5-triazepine derivatives have been synthesized in the past 30 years. Objective: Investigations in the field of heterocyclic chemistry is very important, because there could be several new medicines among the newly synthesized heterocyclic ring systems, which could be used against several diseases which have no remedy yet, for example some types of cancer. The research on antibacterial compounds is also an important field because of spreading of multiresistant pathogens. This review aims to summarize the literature of certain 2,3-benzodiazepine analogues. Conclusion: After a brief historical introduction, various ring systems containing a 2,3-diazepine or a 1,2,5- triazepine ring condensed with five-membered nitrogen heterocycles are disclosed. First, pyrrole-fused compounds are introduced, followed by indole and carbazole derivatives. After that, diverse ring systems containing an imidazole ring are presented. The review is closed with the chemistry of some interesting triazole and tetrazole derivatives. Many of these compounds bear significant biological efficacy.

Synthesis of quinazolines and quinazolinones via palladium-mediated approach

Abstract Quinazoline derivatives have drawn attention in the field of heterocyclic chemistry because of their unique skeleton and interesting biological applications. This review summarizes the recent palladium-catalyzed reactions used to construct quinazoline and its related 4(3H)-quinazolinone analogues. The mechanisms of some Pd-catalyzed reactions are also discussed.

Dedication to Desmond Joseph Brown

This issue of Aust. J. Chem. is dedicated to Desmond Joseph Brown, formerly of the JohnCurtin School ofMedical Research, ANU, whom we always referred to as ‘Des’. An honorary member of the RACI and an eminent organic chemist who influenced the careers of many chemists, Des was a graduate of the University of Sydney and was awarded Ph.D. and D.Sc. degrees by the University of London. His detailed obituary has been published in Chemistry in Australia, July 2014, pp. 28–29. Des’s career (1942–1985) in academic organic chemical research was almost entirely in the field of heterocyclic chemistry, with emphasis in medicinal chemistry. His interest in these fields began during a year of study in Professor Adrien Albert’s ChemotherapyUnit at the University of Sydney. He thenwent to Imperial College, University of London, where he carried out research on heterocyclic analgesics for his Ph.D. degree under the supervision of Dr A. H. Cook and Professor Ian Heilbron. This was followed by a year at University College, University of London, working on pyrimidine and pteridine research. He was then appointed to the Department of Medical Chemistry in the John Curtin School of Medical Research (JCSMR) at the newly establishedAustralianNational University (ANU), where Adrien Albert had the foundation Chair. He assisted Professor Albert in the design of the building in Canberra, which was completed in 1956, and in establishing the department. Des was Professor Albert’s right-hand man until Professor Albert’s retirement in 1972, and later was appointed head of the Medical Chemistry Group in the JCSMRuntil his retirement at the end of 1985. He then became a Visiting Fellow in the Research School of Chemistry (RSC, ANU)where hewas providedwith an office and facilities for writing books (1986 to 2012). The Department of Medical Chemistry consisted of a fourstorey wing of the JCSMR building in which a very large space that spanned three storeyswas designated ‘TheHighLaboratory’. Des was in charge of this area which was used for very large scale syntheses and when the purification of large quantities of chemicals was required. This laboratory was converted to provide more laboratory space to accommodate new areas of research after 1972. Des’s research was mainly in the areas of pyrimidine, purine, and pteridine chemistry, substances that have central biological importance. He published most of his work in several series of papers, but only the first and the last parts of the series are referenced here. These include Improved Syntheses in the Pyrimidine Series (six parts), Simple Pyrimidines (17 parts), PyrimidineReactions (27 parts),TheDimrothRearrangement (18 parts), Isomerizations Akin to the Dimroth Rearrangement (five parts), Purine Studies (19 parts), Pteridine Studies (12 parts), Aza-analogues of Pteridines (eight parts), Triazolopteridines (three parts), and Naphthimidazoles (three parts). Other papers that he wrote did not belong to any series and stood alone. These included papers on triand tetrazolopurinones, a new route to pyrazolo[2,4-b] pyrazine, triazolopyrimidines, and triazolopurines, among several others. An important aspect of Des’s research was the study of the physico-chemical properties of many of the compounds that he, his students, and co-workers prepared. The studies specifically included the ionisation constants of the substances as well as the electronic spectra of the neutral and ionic species, photoelectron spectra of pteridines, and C NMR of tautomerism in N-heterocycles. Together with Adrien Albert and their co-workers, the department had amassed a tremendous amount of physico-chemical data which is now indispensible in the field ofmedicinal chemistry. The amount of data collected and published nowmakes it possible to predict with some degree of accuracy the dissociation constants of ionisable drugs,

Effect of bisphenol-A on the structures and properties of phthalonitrile-based resin containing benzoxazine

Phthalonitrile and benzoxazine have been considered as high-performance materials in the field of heterocyclic chemistry. The polymerization of phthalonitrile and benzoxazine accelerated by active phenolic hydroxyl has attracted wide interests. In this work, self-promoted polymerization behavior and processability of phthalonitrile containing benzoxazine (BA-ph) with bisphenol-A (BPA) were investigated. Results revealed that BA-ph/BPA exhibited representative double- stage curing behaviors corresponding to the ring-opening polymerization of benzoxazine rings and ring-formation polymer- ization of nitrile groups. Compared with that of BA-ph, processability of BA-ph/BPA was improved and could be tuned by varying BPA contents, processing temperature and time. Then BA-ph/BPA/glass fiber (GF) composite laminates were pre- pared. In comparison with that of BA-ph/GF laminates (542 MPa and 25.8 GPa), the flexural strength and modulus were up to 789 MPa and 23.6 GPa, respectively. Moreover, double Tgs were observed at temperature around 200~300°C and 300~380°C, indicating microphase separation during the polymerization of oxazine rings and nitrile groups, confirmed by the scanning electron microscopic (SEM) images. Thermal stabilities demonstrated that all BA-ph/BPA/GF composites exhibited high T10% up to 510°C. The systematic study of BA-ph/BPA system could enrich our knowledge on phthaloni- trile-based resins in industrial applications, especially in the areas which require excellent mechanical properties and high temperature resistance.

Alan Roy Katritzky. 18 August 1928 — 10 February 2014

After a bright start, first in Oxford and then in Cambridge, Alan Katritzky’s scientific career was spent at the University of East Anglia in Norwich, where he became the founding Professor of Chemistry (1962) and at the University of Florida in Gainesville, USA, in the Kenan Chair of Chemistry from 1980 until his death in 2014. For more than 60 years he was a pioneer in the development of the field of heterocyclic chemistry. His work contributed much to the science that underpins the synthetic work of the modern pharmaceutical and agrichemical industries as well as that of dyestuffs and polymers. His research also touched other areas such as physical organic and polymer chemistry, organic reaction mechanisms, spectroscopy, chemical sensors, peptide synthesis, and reactions in water at high temperatures and pressures. Alan Katritzky worked with large cohorts of graduate students and research fellows drawn from across the globe. Their work was reported in nearly 2200 papers published in the primary scientific literature. He was also very active in the publishing field, writing and editing monographs and reviews, maintaining this prodigious level of output until a few days before he died.

ChemInform Abstract: Microwave‐Assisted Synthesis of Benzo‐Fused Seven‐Membered Azaheterocycles

AbstractReview: such as benzodiazepines, benzothiazepines and benzoxazepines; 102 refs.

Naturally Occurring and Synthetic Agents as Potential Anti-Inflammatory and Immunomodulants

Terpenes in general and triterpenes in particular showed anti-inflammatory activity and act as immunomodulators in nutraceutical agents. Antiinflammation, a useful and attractive approach in experimental oncology, helps to investigate the inflammation preventive potential of natural products and synthetic entities. During the course of our research work in natural product chemistry and synthesis of novel structures in the field of heterocyclic chemistry, we found interesting results. In natural product betulinic acid, α-amyrin acetate, lupeol acetate, oleanolic acid, ursolic acid and their derivatives showed interesting potential analgesic and anti-inflammatory activity. In this review specific reference has been made to novel classes and newly discovered compounds in the literature, which exhibited required activities. Indomethacine is a potent synthetic compound, which becomes the basis of novel anti-inflammatory agents. Shen postulated a receptor theory which indicates the physical parameters responsible for anti-inflammatory activity. Attempt has been made to cover almost all the anti-inflammatory agents which fall under the various chemical structural classes of compounds showing required activity. The objective of this review is to compile relevant data on the mechanism of action of terpenes isolated from active ethnomedicinal plants to examine the role terpenoids have in medicinal plants used against inflammatory diseases, especially those in which an immune response is implicated. In addition, a selection of several structurally related compounds has been compiled in order to analyze the possible structural characteristics and relationships between the different types of structures found in triterpenoids. The selection of active species was made on the basis of their immunomodulatory activity, and their role in the resolution of diseases in which the immune system is implicated to examine the mechanism by which they are useful as ethnopharmacological medicines. These terpenes include ursolic acid, oleanolic acid, betulinic acid. This review discusses in detail the preclinical studies conducted with triterpenes and provides an insight into its mechanism of action.

Highlights of the 2009 New South Wales Southern Highlands Conference on Heterocyclic Chemistry

Meetings that foster interaction between academic and industrial researchers, both operating at the forefront of science, serve to stimulate ideas and allow partnerships to develop. The Southern Highlands Conference brings together experts in the field of heterocyclic chemistry and, in this issue, some of the most recent advances are highlighted (The figure shows 2009 Conference student speakers with President Barbara Messerle).

New Bicyclic Amines: Synthesis and SARs of their Action Against the Causative Organisms of Malaria and Sleeping Sickness

Diaryl-substituted bicyclic amines are a scarcely investigated class of compounds. Only few of them are described and their biological activities are reported poorly. During our work in the field of heterocyclic chemistry, we found that 4-dialkylaminobicyclo[2.2.2]octan-2-ones and -ols show antiprotozoal properties against Plasmodium falciparum K(1) and Trypanosoma brucei rhodesiense, the causative organisms of Malaria tropica and of Human African Trypanosomiasis. Therefore, we synthesized over 200 derivatives in order to investigate their antitrypanosomal and antiplasmodial activities as well as their cyctotoxicity using in vitro microplate assays. Even if the target and the mechanism of action of these compounds are still unknown, we can at least provide several structure-activity relationships for this interesting class of compounds. Moreover, we achieved a distinct improvement of their antiplasmodial and antitrypanosomal properties.

Crystal structure of 2-bromobenzoic acid hydrazide, C7H7BrN2O

C7H7BrN2O, monoclinic, P121/c1 (no. 14), a = 12.769(3) A, b = 12.754(3) A, c = 5.026(1) A, = 99.874(4)°, V = 806.5 A 3 , Z =4 ,Rgt(F) = 0.028, wRref(F 2 ) = 0.074, T = 293 K. Source of material The title compound was synthesized by the reaction of ethyl ester of 2-bromobenzoic acid with hydrazine hydrate (80 %) in absolute ethanol. The reaction mixture was refluxed for 7 h. The excess of solvent was distilled off, the residue was filtered and washed with water. Colorless thin needle-shaped single crystals suitable for Xray analysis were obtained by recrystallization from 60 % ethanol. Experimental details While the H atoms bound to N atoms were refined freely due to their importance in hydrogen bonding, the H atoms attached to C atoms were refined using conventional restraints. Discussion Aromatic hydrazides are a very important intermediate especially in the field of heterocyclic chemistry. Aromatic hydrazide have been used for the synthesis of various biologically active five membered heterocycles such as 2,5-disubstituated-1,3,4oxadiazoles, 5-substituted-2-mercapto-1,3,4-oxadiazoles etc. Due to its versatilities in the synthesis of various heterocyclic compounds, we have synthesized the title compound and report its structure. The r.m.s. deviation from plane is 0.678 A in the molecular structure of the title compound. Within phenyl ring, the bond lengths lie between 1.376(4) A and 1.386(3) A highlighting the aromatic character. The valence angle C2–C1–C6 of 121.1(2)° is larger than the standard value (120°). The opening of this angle is due to the presence of the bromo group on C1, which involves a decrease of the ring angles on C1 (118.2 (2)°) and C6 (118.2(2)°). The C7—O1 bond distance (1.225(3) A) is compatible with respective distances in a related structure [2] and smaller than those usually observed in carboxylic acids (1.365 A). The structure is influenced by quite interesting intra- and intermolecular hydrogen bonding which stabilizes the whole crystal structure.

How Have We Found Any New Reactions in the Field of the Heterocyclic Chemistry?

AbstractFor Abstract see ChemInform Abstract in Full Text.

How have we found any new reactions in the field of the heterocyclic chemistry?

This review describes the discovery of new reactions in the field of heterocyclic chemistry. The reactions taken as typical examples involve 1) the photochemical ring transformations of quinolines to indole rings, 2) the ring transformations of indoles to quinazoline and quinoxaline rings, 3) the ring expansion reactions of indoles to 1H-1-benzazepines, 4) the intramolecular photo[2+2]cycloaddition reactions of 2- or 3-alkenyloxy-(or amino-)cyclohex-2-en-1-ones, 5) the syntheses of the nitrogen-containing heterocycles using the cyclizations of N-alkenylcarbamoylmethyl radicals, and 6) the general syntheses of bridged azabicyclic compounds using radical translocation/cyclization reactions. Modification of the water-soluble aminating agent hydroxylamine-O-sulfonic acid to the more powerful aminating agent O-mesitylenesulfonylhydroxylamine is also described.

7-Ethoxycarbonylmethyl-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine

The crystal structure of the title ester, ethyl 5-methyl-1,2,4-triazolo[1,5-a]pyrimidine-7-acetate, C10H12N4O2, is described. In the field of heterocyclic chemistry, the prospects offered for the design of antiviral agents, as well as the chemistry of interaction of N-bridged purine analogue ligands with heavy metals, are of biological and environmental importance. This study has elucidated the isomeric structure of a heterocyclic product of the condensation of 3-amino-1,2,4-triazole and 4-hydroxy-6-methyl-2H-pyran-2-one (triacetic acid lactone).

New antitumor agents from inhibitors of folate-dependent enzymes

This lecture summarizes our recent investigations in folate analogue chemistry, which have resulted in the synthesis of several extremely promising chemotherapeutic agents for the treatment of solid tumors. Much of this work has been published previously, this review lecture is concerned with some of the chemical developments of interest in the field of heterocyclic chemistry.