Synthesis Of Nitrogen-Containing Heterocyclic Compounds Via Multi-Component Reaction

Heterocycles constitute the largest diversity of organic molecules of chemical, biomedical,and industrial significance. They are also among the most frequently encountered scaffolds innumerous drugs and pharmaceutically relevant substances. In the past several decades, aseries of libraries consisting of heterocycles have been successfully established for thestructure-activity-relationship studies (SAR) for drug design and synthesis. While thediversity-oriented synthesis (DOS) continues to be an area of importance at the interface oforganic synthesis and chemical biology, more efficient multi-component domino reactions(MDRs) for the synthesis of a series of heterocycles, particularly functionalizedmulti-heterocycles, have been in high demand. Multi-component domino reactions (MDRs)serve as a rapid and efficient tool for the synthesis of versatile heterocycles, particularly thosecontaining structural diversity and complexity, by a one-pot operation. These reactions candramatically reduce the generation of chemical wastes, costs of starting materials, and the useof energy and manpower. Moreover, the reaction period can be substantially shortened. ThisReview covers recent advances on multi-component domino reactions for the construction offive-, six-, and seven-membered heterocyclic skeletons and their multi-cyclic derivatives.In the context of sustainable chemistry, the design and development of sequencesallowing highly selective access to elaborated molecular scaffolds while combining structuraldiversity with eco-compatibility, are great challenges for organic chemists. Multi-componentreactions (MCRs) are now well-established approaches to reach this near ideal goal. Thisdissertation will be divided in four sections. Most of compounds were characterized by IR,1HNMR and13C NMR.Firstly, Indole and indoline fragments are important moieties of a large number of naturalbiologically active compounds, and some of indolines, spiro-annulated with heterocycles inthe3-position, have shown high biological activity. Substituted2-amino-4H-pyrans take asignificant place among the6-memberedoxygen-containing heterocycles. Some of thempossess anticancer and antimicrobial activity; others were employed in syntheses of bloodanticoagulant warfarin and tacrine analogs (cholinesterase inhibitors). We herein report a new method for the synthesis of2-amino-5-oxo-indols by the one-pot, three-component reaction ofan isatin, malononitrile and dimedone in the presence of a catalytic amount ofhexamethyleneteramine in water.In recent years, the use of polyethylene glycol as a reaction medium has gainedconsiderable interest in organic synthesis due to its many advantages from environmental,economical, and safety standpoints. It is non-toxic, inexpensive, non-volatile, thermally stable,biologically acceptable, and eco-friendly, and allows many useful organic transformations tobe performed under mild reaction conditions, such as coupling, addition, substitution,condensation, oxidation, reduction, and multi-component reaction. In a continuation of ourinterest in developing more efficient and environmental benign methodologies, we reportherein a simple and facile procedure for the synthesis of pyrazolophthalazinyl spirooxindolesthrough one-pot three-component reaction of isatin, malononitrile or cyanoacetic ester andphthalhydrazide catalyzed by NiCl2in PEG600.The1,2-dihydroquinazoline compound family has a rich pharmacology with reportednitric oxide synthase (NOS) inhibitors and antiinflammatory efficiency. We found that themixtures of sugars, sugar alcohols or citric acid with urea and inorganic salts form stablemelts when heated to70oC. The results recommend the non-toxic sugar–urea–salt melts asmore sustainable reaction media for chemical transformations.4-substituted-spiro-1,2-dihydr-oquinazolines and related compounds were synthesized by direct reaction of2-aminobenzop-henones, isatin, or1,2-diketone derivatives and ammonium acetate in the presence of thenon-toxic sugar–urea–salt melts. Excellent conversion of starting materials was achieved tothe desired1,2-dihydro-quinazoline products.Pyrimidine compounds which present in many natural products, are important drugmolecule structural units. We report herein a simple and facile procedure for the synthesis ofpyrimidine compounds through one-pot three-component reaction of2-aminobenzophenones,aldehydes and ammonium acetate in the presence of the non-toxic sugar–urea–salt melts.As mentioned above four types of material containing nitrogen heterocyclic which playsan important role are important compounds, so the research on nitrogen heterocycliccompounds is of great significance. We on the basis of previous research successfully synthesized the four substances, using “one-pot” of multi-component reactions in water, PEG600and the non-toxic sugar–urea–salt melts, using cheap and easily obtained catalyst. Theadvantages of the method are suitable for various substrates, mild condition, operation andexperimental simplicity, high yield. It will promote the development of organic synthesischemistry.