Reactivity heterocydes

Price W. A., Silva A. M. S., Cavaleiro JAS 2-Styrylchromones Biological Action, Synthesis and Reactivity Heterocydes 1993 36 2601-2611... 

In this section, only salient features of the synthesis, physicochemical properties, and reactivity of major derivatives of 2-aminothiazole and 2-imino-4-thiazoline are summarized. Further details on each compound are found in associated references collected in Section VII. The synthetic methods reported in this section exclude heterocydization methods treated in Chapter II but given in specific references found in Section VII. 

Organic Synthesis Theory and Applications Progress in Heterocydic Chemistry Progress in Macrocydic Chemistry Progress in Physical Organic Chemistry Reactive Intermediates (Plenum)... 

Both, the Kolbe-Schmitt reaction and the dialkyl carbonate route may be beneficial, notably when taking into account the former syntheses used to produce these carboxylato derivatives. Prior to the study of Tommasi et al., the formation of imi-dazolium carboxylates via highly reactive N-heterocydic carbenes (NHC) had been reported, although this rather challenging synthesis could not be extended to an industrial scale. The synthesis of l,3-diisopropyl-4,5-dimethyl-imidazohum-... 

The intramolecular Alder-ene reaction (enyne cydoisomerization reaction) with alkynes as the enophiles has found wide application compared with diene systems. The reason may be the ready chemo-differentiation between alkene and alkyne functionality and the more reactive alkyne moiety. Furthermore, the diene nature of the products will promote further applications such as Diels-Alder reactions in organic synthesis. Over the past two decades the transition metal-catalyzed Alder-ene cycloisomerization of l,n-enynes (typically n= 6, 7) has emerged as a very powerful method for constructing complicated carbo- or heterocydic frameworks. The transition metals for this transformation indude Pd, Pt, Co, Ru, Ni-Cr, and Rh. Lewis acid-promoted cydoisomerization of activated enynes has also been reported [11],... 

The chemistry of pyrrole, furan, and thiophene is similar to that of activated benzene rings. In general, however, the heterocydes are more reactive toward electrophiles than benzene rings are, and low temperatures are often necessary to control the reactions. Halogenation, nitration, sulfonation, and... 

Thiophene is a usefiil template for four-carbon homologation via reduction [9], as well as a bioisostere of the benzene ring and other heterocydes in medicinal chemistry. Thiophene is a n-electron-excessive heterocycle. It favors electrophilic substitution, which, similar to metalation, takes place preferably at the a-positions due to the electronegativity of the sulfiir atom [10]. In comparison to the oxygen atom in fiiran, the sulfiir atom in thiophene has lower electronegativity, so its lone pair electtons are more effectively incorporated into the aromatic system. The aromaticity of thiophene is in between that of benzene and fiiran. As a consequence, the difference in reactivity of a-halothiophenes and 3-halothiophenes is not as pronounced as that of the corresponding halofiirans. 

The relationship between A -heterocydic carbene structure and reactivity... 

Replacing the hydroxyl group with an amido group provides access to the corresponding nitrogen heterocydes, the 3-pyrrolinones [40]. The example in Equation 1.42 highlights the chemoselectivity of the process since normally the diene moiety of substrate 39 is considered the more reactive functionality. 

The last chapter concerns the chemistry of triphosphabenzenes and valence isomers reviewed by H. Heydt. The remarkable versatfle reactivity of 1,3,5 triphos-phinines through a fruitful and smart organophosphorus chemistry and leading to a large variety of new phosphorus heterocydes is presented. 

The high reactivity of ortho-benzyne is also evident in 1,3-dipolar cycloadditions. The reaction is an extremely useful route to benzo-fused five-membered ring heterocydes. For example, azides give benzotriazoles, diazo compounds give (after... 

This general reactivity has been used recently to obtain benzocondensed heterocydes (2012S547), 1,2,4-triazoles (2010JOC8724), and fluorinated oxadiazin-6-ones (2009TL1472). 

Over the past several decades, research in the field of palladium catalysis has resulted in the development of a myriad of transformations that provide access to saturated nitrogen heterocycles. Many of these transformations effect the formation of several bonds, and/or proceed with good to excellent levels of stereocontrol. Despite the many advances made in this field, discoveries of new reactivity are still being reported with great frequency, and this promises to remain a fruitful area of research for many years to come. In particular, the development of new palladium catalysts will likely lead to improvements in the scope of existing transformations, and will also open up new reaction pathways that can be applied to unsolved problems in heterocydic chemistry. 

The cross-coupling reactions of hydrazines with aryl halides to give substituted hydrazines is very important from the point of view of nitrogen heterocyde synthesis (for example, indoles, indazoles, pyrazoles, and aryltriazoles, and before this report by Straddiotto s group [28a], there was no literature method for the Pd-catalyzed cross-coupling of hydrazine to aryl electrophiles. Hydrazines are difficult substrates because of their reducing power and the reactivity of the mono-arylated hydrazine product to further arylation. 

The SnAt reactivity of the quinazoline system offers synthetic applications for this heterocyde. For instance, 4-chloro-2-phenylquinazoline (49), by reaction with pheno-lates, is converted into the 4-(aryloxy)quinazoIine 50, which undergoes a Chapman rearrangement at 300 °C with a 1,3-migration of the aryl residue to N-3 forming the 3-arylquinazolin-4(3H)-one 51. The latter hydrolyzes with aqueous add to form benzoxazinone 52 and a primary arylamine ... 

The replacement of a heterocydic hydroxyl group (generally in the 0X0 form, Section II,E,2,e) with thioxo or chloro groups by phosphorus pentasulfide or phosphorus oxychloride presumably proceeds through nucleophilic substitution (frequently add-catalyzed, 21 and 86) of thiophosphoryloxy and dichlorophosphoryloxy intermediates. The 4-position in pyrimidine is more reactive than the 2-position and, at low temperature, this type of thionation of pyrimidine-2,4-diones is specific for the 4-position. In 6W-triazine... 

Garrett, C.E. and Fu, G.C. (1998) Nudeophilic catalysis with Jt-bound nitrogen heterocydes synthesis of the first ruthenium catalysts and comparison of the reactivity and the enantioselectivity of ruthenium and iron complexes. J. Am. Chem. Soc., 120, 7479-7483. 

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