Showing papers in "Advances in Heterocyclic Chemistry in 2007"

Current Tröger's Base Chemistry

Abstract: Publisher Summary This chapter summarizes Troger's bases (TBs). It describes its historical developments, revival, synthesis and mechanism of formation, reactivity, physicochemical properties, and its uses and applications. The chapter also provides a brief discussion about pseudo-TBs. It is observed that in principle, any aromatic or heteroaromatic amine can serve as a possible precursor of TBs. TB derivatives are generally viewed as anomalous chiral substances with two nitrogen-containing stereogenic centers. TB derivatives are considered highly useful synthetic building blocks. The common properties of TBs include: biomimetic molecular recognition processes and complex interactions with important biomolecules. TBs represent chiral tectons exhibiting a wide range of applications, such as (1) the TB scaffold is used extensively for the construction of molecular receptors, (2) unique geometry of TB is extensively used in preparing macrocycles, (3) TB derivatives are also considered as hosts for cyclic urea and adenine derivatives, and (4) TB analogs promote investigations of second harmonic reflections from chiral surfaces.

Recent Progress in 1,2,4-Triazolo[1,5-a]pyrimidine Chemistry

Abstract: Publisher Summary 1,2,4-Triazolo[1,5-a]pyrimidines (TPs) play an important role in pharmaceutics, agrochemistry, photography, and other fields. They attract attention in synthetic, analytical, and theoretical chemistry. Isomeric 1,2,4-triazolo[4,3-a]pyrimidines and partially reduced TPs are mentioned only when they are precursors, potential intermediates, or reaction products of TPs. By far, the most TP syntheses are condensations of dinucleophilic 5-amino-1,2,4-triazoles (ATs) with 1,3-bifunctional synthons as in the formation of TP 2. Quantum-chemical calculations on TPs, particularly oxo compounds, were performed by several groups. A new aromaticity index was calculated for heterocyclic compounds. Comparison of the index of 2-ribosyl-5,7-dimethyl TP with that of the isomeric compound suggests that the driving force for the Dimroth rearrangement of the latter substance is the increase in aromatic character. The chapter discusses the molecular dimensions, molecular spectra, thermodynamic properties, tautomerism, and betain and mesoionic structures of TPs. The reactivity of TPs are described including triazolopyrimidines as bases and acids, ring alkylation, electrophilic reactions at carbon ring atoms, nucleophilic addition, ring cleavage, nucleophilic substitution of functional groups at the rings introduction and transformation of individual substituents, and reactivity of side chains. The pharmaceutical and agrochemical uses are described. The uses in information recording are also discussed.

The Chemistry of Thienopyridines

Abstract: Publisher Summary It is noted that the derivatives of pyridine attract significant interest because of their great practical usefulness, primarily, due to their various biological activities. Among pyridine derivatives, the fused analogs are considered extremely important. These factors are supplemented with variations due to annulation at different positions of the heterocyclic fragments. Further, among these heterocyclic systems, thienopyridines occupy a special place. This chapter describes the synthesis, reactivity, and biological activities of isomeric thienopyridines. The chapter considers six isomeric thienopyridine structures characterized by different annulation modes— namely, (1) thieno[2,3- b ]pyridine, (2) thieno[3,2- b ]pyridine, (3) thieno[2,3- c ]pyridine, (4) thieno[3,2- c ]pyridine, (5) thieno[3,4- b ]pyridine, and (6) thieno[3,4- c ]pyridine. The high pharmacological potential of thienopyridine derivatives stimulates the elaboration of new ingenious methods, nonconventional approaches, and regio- and stereoselective procedures that essentially extends the synthetic scope of the chemistry of nitrogen heterocycles. The unexhausted potential of thienopyridine derivatives as synthons also attracts considerable attention of organic chemists, because such compounds allow transformations that have been previously inaccessible.

The Synthesis of Heterocycles Using Cascade Chemistry

Abstract: Publisher Summary This chapter reviews the kind of reactions that have been sequenced into cascades to produce heterocyclic molecules. The fact that multiple reactions give rise to a cascade sequence makes the categorization of these processes difficult. From the selective sampling of cascade reactions for the synthesis of heterocyclic molecules that has been outlined in this chapter, it is clear that virtually any reaction can be incorporated into a tandem sequence. Many of these cascades rapidly construct hetero-polycyclic systems that are difficult to produce in other ways. Several cascade sequences for heterocyclic synthesis have been well explored: (1) Padwa's rhodium carbene-initiated dipolar cycloadditions, (2) Denmark's nitroalkene [4+2]/[3+2]-cycloadditions, (3) Overman's Aza-Cope/Mannich cascade, (4) Bunce's conjugate addition strategy, (5) Molina's Aza-Wittig/heterocumulene cyclization reactions, and (6) Grigg's use of relays and switches in palladium-mediated cascades have matured into significant synthetic tools. Familiar multi-component reactions, such as the Ugi reaction, are being used in interesting ways. Other sequences show tremendous promise. Fu's asymmetric Kinugasa reaction, indium-initiated radical cascades, Buchwald's copper catalyzed N-arylation reactions, Trost's alkyne heterocyclization, and Hoveyda and Schrock tandem AROM/RCM reactions all provide improvements in stereoselectivity and involve the use of environmentally benign reagents. Continued development of these cascade reactions will have a significant impact on the processes used to make heterocyclic compounds on an industrial scale.

Nucleophilic Aromatic Substitution of Hydrogen as a Tool for Heterocyclic Ring Annulation

Abstract: Publisher Summary SNH methodology finds significant use in organic synthesis. A major advantage of this methodology is that it eliminates the necessity of first introducing a good leaving group into an aromatic substrate. Moreover, in classical SN ipso reactions an acid, such as HHal, H2SO4 or HNO2 is normally liberated that has to be scavenged. However, in SNH processes, a water molecule is typically formed that can contribute to “green chemistry.” This chapter deals with SNH cyclizations. SNH based heterocyclizations allow the synthesis of a great variety of heterocyclic structures differing in ring size, number of heteroatoms and their type, and degree of unsaturation. Various arenes and hetarenes with appropriate electron deficiency can be used as substrates. In context to future prospects, it is observed that a large number of known SNH cyclizations deals with the pyrrole ring closure, therefore search for new substrates, reagents, and cyclization schemes for the annulation of other heterocyclic rings is desirable. It is also important to optimize reaction conditions as many existing transformations do not provide high enough yields.

Pyrazol-3-ones. Part III: Reactivity of the Ring Substituents

Abstract: Publisher Summary All pyrazolones are named according to the International Union of Pure and Applied Chemistry (IUPAC) recommendations as pyrazol-3-ones and not as pyrazol-5-ones. The IUPAC nomenclature numbers the ring clockwise, whereas most organic chemists are used to an anti-clockwise numbering. Alkylation of pyrazol-3-ones usually occurs not only on side-chain substituents, such as primary amino groups, but also on the nitrogen atom of the unsubstituted lactam group. Alkylation can also occur on a stabilized carbanion generated from a methyl group by a strong base. Most of the acylation reactions are carried out with 4-amino-1,2-dihydro-1,5-dimethyl-2- phenyl-3H-pyrazol-3-one (4-aminoantipyrine). The acid chlorides are prepared separately or generated in situ from the corresponding carboxylic acid in the presence of the aminopyrazol-3-ones. The only halogenation reactions of the ring substituents of pyrazol-3-ones known are those with bromine, N-bromosuccinimide, and hydrogen bromide. Sulfonation of 5-aminopyrazol-3-ones is described. Coupling the diazonium salts with carbon nucleophiles is the most common reaction. Condensation reactions are discussed. One of the categories of reactions may involve nucleophilic addition either by or to the pyrazol-3-one side-group. A variety of nucleophilic substitution reactions are discussed. Pyrazol-3-ones are oxidized by a variety of oxidizing agents. The reduction of functional groups, such as aldehyde, nitro, nitroso, alkene, and imino as well as deamination of amines and cleavage of amides are accomplished by various reducing agents without affecting the pyrazol-3-one ring. Some miscellaneous reactions are discussed.

Organometallic Chemistry of Polypyridine Ligands I

Abstract: Publisher Summary This chapter deals with organometallic complexes of non-transition metals and those of Groups IIIB–VIB. 2,2′-bipyridine, 1,10-phenanthroline, and their derivatives and analogues are chemically stable π-acidic ligands that tend to form complexes with metals in their lower oxidation states. It is noted that 2,2′-bipyridine and its derivatives are the most widely used ligands. They act as classical chelating ligands and serve as electron reservoirs. Organometallic complexes of 2,2′-bipyridine are prominent catalysts of electrochemical and photochemical reduction of carbon dioxide, as well as of the water gas shift reaction. Polypyridyl organometallic complexes serve as building blocks in supramolecular structures that in combination with their photochemical properties make them extremely attractive materials of modern electronics. The chapter describes the complexes of polypyridine ligands with scandium, titanium, chromium, and vanadium group metals. Polypyridine ligands essentially stabilize the complexes of metals of Groups VB and VIB in their low oxidation states forming stable species, with interesting photochemical and electrochemical properties. They form chelates with η2-coordination and all the chemical changes occur in the rest of the complex.

Aminoisoxazoles: Preparations and Utility in the Synthesis of Condensed Systems

Abstract: Publisher Summary This chapter deals with the chemistry of aminoisoxazoles(AI), which is a subsection of isoxazole chemistry. The available amino group changes distinctly the properties and reactivity of the isoxazole ring, and some reactions and rearrangements that are unusual in isoxazole chemistry become typical. An amino group is convenient in combinatorial chemistry and facilitates the use of these compounds in modern drug discovery. The studies on AI have been mainly concerned with the biological activities and the preparation of fused heterocyclic systems, such as isoxazolopyridines, isoxazolopyrimidines, and isoxazolodiazepines. AI-based condensed heterocyclic systems are more biologically promising than AI themselves. Indeed, AI derivatives possess cytostatic, antibacterial, herbicidal, immunological, hypocholesterolemic, and anticonvulsant activities among other activities.

Peri-Annulated Heterocyclic Systems. Part I

Abstract: Publisher Summary The chapter presents various aspects of the chemistry of peri-fused heterocyclic systems taking into account the new findings. The chapter discusses the previously developed sequence, describing successively the compounds with larger heterocycles, with increasing number of heteroatoms in the heteroatom order N,O,S, and occasionally other heteroatoms. This chapter draws attention to the peri-fused heterocyclic naphthalene derivatives with a four-membered heterocyclic ring. Those peri-annulated heterocycles with a closed π-system that possess a double bond or another π- or p-electron “bridge” situated in the peri-position of the naphthalene ring opposite to the heterocycle should be set apart. A large number of stable representatives of four-membered heterocycles with nitrogen or oxygen ring heteroatom are described, among them also their benzoannulated derivatives. The chapter describes the peri-annulated heterocyclic naphthalene derivatives with a four-membered hetero ring— namely, (1)Naphth[1,8-bc]azete, (2)Naphtho[1,8-bc]phosphate, (3)Naphth[1,8-bc]oxete, (4)Naphtho[1,8-bc]thiete and its S-Oxides (5)Naphtho[1,8-bc]borete and (6)Naphtho[1,8-bc]silete .

Isothiazolium Salts and Their Use as Components for the Synthesis of S,N-Heterocycles

Abstract: Publisher Summary This chapter presents a complete picture of the chemistry of monocyclic, bicyclic, benzocyclic, and heterocyclic annulated isothiazolium salts 5–15. Several new alternatives to the classical methods of synthesis have been developed. The chapter deals with isothiazole and its derivatives that have a broad range of biological activities. Isothiazol-3(2H)-ones 1 are potent industrial microbicides because of their antifungal and antibacterial activities. The development of a new and efficient method for the synthesis of functionalized monocyclic sultams has attracted much attention due to their importance in biological and pharmacological research. The first monocyclic 2, 3-dihydroisothiazole 1, 1-dioxides 4, without the 3-oxogroup but with anti-HIV-1 activity have been recently synthesized. Patents are included, if they reveal the new synthetic aspects or interesting applications of formed novel S,N-heterocycles.