Synthesis of Heterocyclic Compounds

Heterocyclic chemistry has benefited substantially from MW-expedited processes developed over the last decade. An exhaustive overview is provided elsewhere in this book [97, 98] limited solvent-free chemistry utilizing mineral-supported reagents is covered in this section. 

Solvent-free cyclization of converting N-aryl iminodithiazoles into 2-cyano ben-zothiazoles under the action of MW has been investigated to develop environmentally friendly procedures for synthesis of heterocyclic molecules for which traditional methods failed or are less attractive [174], 

A solvent-free MW-promoted one-pot synthesis of fluorinated 2,3-dihydro-l,5-benzothiazepines by Michael addition followed by dehydrative cyclization has 

Pharmacologically important natural 2-aroylbenzofurans are easily obtainable under basic solvent-free conditions from a-tosyl oxyketones and salicylaldehydes 

Reaction of anthranilic acid derivatives with formamide on silica gel, acidic alumina, or montmorillonite KIO under the action of MW irradiation generates quina-zolines in good yields [181]. Another one-step MW method for preparation of sub- 

Heterocyclic compounds are immensely important due to their wide spectrum of biological activity. A number of diverse heterocyclic systems have been synthesised. For details sec Sec. 13.3. 

The use of microwaves has led to substantial savings in time for many syntheses in the laboratory as well as in industry. Microwave induced reactions can be carried out in water or organic solvents. The organic solvents if used, are required in very small quantities. The most important feature of microwaves induced reactions is that these can also be carried out in the solid state, i.e., without the use of any solvent. 

Shui-Teinchem, Shyh-Homgchiou and Kung-Tsungwang, J. Chem. Soc. Chem. Commun., 1990,807. 

Monteux, A. Petit, J. Aizpurua, E. Domingulz and C. Plomu, Tetrahedron Lerr., 1996,37,8177. 

Kataoka, M. Yoskioka, Y. Sendo, S. Nishitant, S. Hirai, T. Maeda and W. Nagata, Tetrahedron Lett., 1979,2793. 

Heterocyclic compounds are indispensable in recent far-reaching developments in the material and biological sciences because they can be used as a substructure in functional materials, agrochemicals, and pharmaceuticals. Transition-metal catalysis continues to be a fruitful source of new methods for the synthesis of heterocyclic compounds, since transition-metal catalysts can be used to construct complex structures directly from easily accessible starting materials under neutral and mild reaction conditions. The cycloaddition of unsaturated molecules is one of the most straightforward and atom-economical reactions for constructing substituted heterocyclic compounds [20]. 

Wakatsuki and Yamazaki pioneered the Co-catalyzed reaction of alkynes with nitriles to give substituted pyridines [21], Recently, there have been extensive studies on the development of transition-metal catalysts other than Co. Ru [22], Rh [23], and Ni [24] catalysts have been reported. Details are provided in other sections. 

One of the most reliable methods for the construction of an oligoheteroarene structure is the transition-metal-catalyzed cross-coupling reaction [26]. However, a problem to be overcome remains in the cross-coupling. The installation of a metal group into heteroaromatic compounds is often dififlcult because of problems with the stability of the resulting heteroaromatic metal reagent [27]. For example, 2-pyridyl boronic acid and its esters are easily decomposed by proton [28]. In addition to this problem with stability, the transmetallation of an electron-deficient heteroaromatic boron reagent to palladium is relatively slow [29]. 

Cycloaddition offers a convenient approach to oligoheteroarenes that are not easily accessible by cross-coupling. An advantage of this new methodology is that construction and connection of the ring can be performed in a single operation from easily accessible and stable materials without a metallation step. 

The transition-metal-catalyzed [2- -2-1-2] cycloaddition of two molecules of alkyne with one molecule of isocyanate is an atom-economical and environmentally benign reaction for the synthesis of 2-pyridone, which is a valuable heterocycle for 

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The protonated azirine system has also been utilized for the synthesis of heterocyclic compounds (67JA44S6). Thus, treatment of (199) with anhydrous perchloric acid and acetone or acetonitrile gave the oxazolinium perchlorate (207) and the imidazolinium perchlorate (209), respectively. The mechanism of these reactions involves 1,3-bond cleavage of the protonated azirine and reaction with the carbonyl group (or nitrile) to produce a resonance-stabilized carbonium-oxonium ion (or carbonium-nitrilium ion), followed by attack of the nitrogen unshared pair jf electrons to complete the cyclization. 

Intramolecular cyclization in perfluoroaromanc systems proves useful for the synthesis of heterocyclic compounds [72] For example, the Fischer indole synthesis, which normally requires the presence of an ortho proton, occurs satisfactonly with an ortho fluonne in theperfluoronaphthalene senes [73] (equation 37)... 

Hydrazine and its derivatives find considerable use in the synthesis of biologically active materials, dyestuff intermediates and other organic derivatives. Reactions of aldehydes to form hydrazides (RCH=NNH2) and azines (RCH=NN=CHR) are well known in organic chemistry, as is the use of hydrazine and its derivatives in the synthesis of heterocyclic compounds. 

Ring-chain transformations and their application in the synthesis of heterocyclic compounds 99MI31. 

Solvent-free synthesis of heterocyclic compounds using microwaves 99JHC1565. 

Synthesis of heterocyclic compounds using hypervalent iodine reagents 98AHC(69)1. 

Dihydrofurans in synthesis of heterocyclic compounds 97UK151. Hydrofurans in syntheses of heterocycles 97KGS723. 

Tfctcro-Diels Alder reaction is a powerful methodology in the synthesis of heterocyclic compounds. Using the high pressure technique has greatly extended the synthetic applications of this methodology. 

The synthesis of heterocyclic compounds using transition metals and using heterocyclic compounds as intermediates in the synthesis of other organic compounds will bean additional feature of each volume. Pathways involving the destruction of heterocyclic rings will also be dealt with so that the synthesis of specifically functionalized non-heterocyclic molecules can be designed. Each volume in this series will provide an overall picture of heterocyclic compounds... 

Glutaconaldehyde anion serves as an interesting intermediate for the synthesis of heterocyclic compounds. The parent pyrylium perchlorate has been prepared from glutaconaldehyde and 70% perchloric acid in ether at -55°.° The reaction of glutaconaldehyde anion with alkyl and aryl isothiocyanates and... 

Itoh K, Yamamoto Y (2004) Ruthenium Catalyzed Synthesis of Heterocyclic Compounds. 11 249-276... 

Orru, R.V.A. St de Greef, M. (2003) Recent Advances in Solution-Phase Multicomponent Methodology for the Synthesis of Heterocyclic Compounds. Synthesis, 1471-1499. 

In a paper concerned primarily with the use of epoxyalkylphosphonates in the synthesis of heterocyclic compounds, the (epoxyalkyl)phosphonic esters have been obtained, accompanied by (2-oxoalkyl)phosphonic esters (81) in the reaction... 

As already described for the all-carbon-Diels-Alder reaction, a hetero-Diels-Alder reaction can also be followed by a retro-hetero-Diels-Alder reaction. This type of process, which has long been known, is especially useful for the synthesis of heterocyclic compounds. Sanchez and coworkers described the synthesis of 2-aminopyridines [48] and 2-glycosylaminopyridines 4-144 [49] by a hetero-Diels-Alder reaction of pyrimidines as 4-143 with dimethyl acetylenedicarboxylate followed by extrusion of methyl isocyanate to give the desired compounds (Scheme 4.30). This approach represents a new method for the synthesis of 2-aminopyridine nucleoside analogues. In addition to the pyridines 4-144, small amounts of pyrimidine derivatives are formed by a Michael-type addition. 

The combination of silyl enol ethers and fluoride ion provides more reactive anions to give alkylated nitro compounds in good yields after oxidation with DDQ, as shown in Eq. 9.22.36 This process provides a new method for synthesis of indoles and oxyindoles (see Chapter 10, Synthesis of Heterocyclic Compounds). 

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