Heterocyclic compounds Pyrrole

Aromatic sextets can also be present in five- and seven-membered rings. If a five-membered ring has two double bonds and the fifth atom possesses an unshared pair of electrons, the ring has five p orbitals that can overlap to create five new orbitals— three bonding and two antibonding (Fig. 2.6). There are six electrons for these orbitals the four p orbitals of the double bonds each contribute one and the filled orbital contributes the other two. The six electrons occupy the bonding orbitals and constitute an aromatic sextet. The heterocyclic compounds pyrrole, thiophene, and... 

M. P. Sammes in Chemistry of Heterocyclic Compounds Pyrroles Part 1 , Wiley-Interscience, New York, 1990, vol. 48, p.549. 

Commonly used secondary amines are the heterocyclic compounds pyrrole dine and morpholine ... 

Use Substitute for tartaric acid, sequesterant for metal ions (calcium, iron), retards hardening of concrete intermediate for synthesis of heterocyclic compounds (pyrroles). 

Bean GP (1990) In Jones RA (ed) Chemistry of heterocyclic compounds, pyrroles. Wiley, New York, pp 105-294... 

Cyclic compounds that contain at least one atom other than carbon within their ring are called heterocyclic compounds, and those that possess aromatic stability are called het erocyclic aromatic compounds Some representative heterocyclic aromatic compounds are pyridine pyrrole furan and thiophene The structures and the lUPAC numbering system used m naming their derivatives are shown In their stability and chemical behav lor all these compounds resemble benzene more than they resemble alkenes... 

The foregoing examples show that the nucleophilic attack to nitroarenes at theorr/io-posidcn followed by cyclizadon is a generid method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion dedved from ethyl isocyanoacetate as the reacdve anion for the preparadon of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyriirddines depending on the stnicture of nitroarenes fEqs. 9.56 and9.57. The synthesis of pyrroles is discussed in detail in Chapter 10. 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

Hoesch reaction. In most cases, a Lewis acid is necessary zinc chloride is the most common. The reaction is generally useful only with phenols, phenolic ethers, and some reactive heterocyclic compounds (e.g., pyrrole), but it can be extended to aromatic amines by the use of BCls. Acylation in the case of amines is regioselectively ortho. Monohydric phenols, however, generally do not give ketones " but are attacked at the oxygen to produce imino esters. Many nitriles... 

Various heterocyclic compounds contribute particular flavor and aroma notes some examples follow Furfural is haylike,15 N-furyl pyrroles pos-... 

The analytical data obtained, particularly by the PUMA mass spectrometer on board Vega 1 during the flyby, indicate the presence of a large number of linear and cyclic carbon compounds, such as olefins, alkynes, imines, nitriles, aldehydes and carboxylic acids, but also heterocyclic compounds (pyridines, pyrroles, purines and pyrimidines) and some benzene derivatives no amino acids, alcohols or saturated hydrocarbons are, however, present (Kissel and Krueger, 1987 Krueger and Kissel, 1987). 

Heteroatom transfer in metallacyclopentadienes was first developed in the context of cobalt chemistry in the mid-1970s [27]. Cobaltacyclopentadienes were converted into various five-membered heterocyclic compounds such as pyrrole and thiophene, and into six-mem-bered heterocyclic compounds such as pyridine and pyridone derivatives. In the case of zirconacydopentadienes, the heteroatom compound must bear at least two halide substituents, since the Cp2Zr moiety is re-converted to the stable Cp2ZrX2. Indeed, this is the driving force behind the heteroatom transfer of zirconacydopentadienes. 

Our study of heterocyclic compounds is directed primarily to an understanding of their reactivity and importance in biochemistry and medicine. The synthesis of aromatic heterocycles is not, therefore, a main theme, but it is useful to consider just a few examples to underline the application of reactions we have considered in earlier chapters. From the beginning, we should appreciate that the synthesis of substituted heterocycles is probably not best achieved by carrying out substitution reactions on the simple heterocycle. It is often much easier and more convenient to design the synthesis so that the heterocycle already carries the required substituents, or has easily modified functions. We can consider two main approaches for heterocycle synthesis, here using pyridine and pyrrole as targets. 

Oxime derivatives of heterocyclic compounds, such as pyrrole and quinoline, were proposed as anti-inflammatory agents, probably due to their ability to inhibit the biosynthesis of leukotrienes . Inhibition of 5-lipogenase by oximes of biphenyl sulfides , and by 0-aIkylcarboxylate oximes of indole " , were suggested as key leads for the development of efficient anti-inflammatory drugs. 

Pyrrole A nitrogen-containing, heterocyclic compound found at low concentrations in crude. Pyrrole can readily polymerize in the presence of light to form dark-brown compounds. Pyrrole derivatives, such as indole, have been identified as sources which can lead to darkening of fuel color and eventual deposit formation. 

Pyrroles, indoles, pyridines, quinolines, and pyrazines are examples of N-hetero-cycles that are produced as fragrance and flavor substances. Thiazoles and dithiazines are examples of nitrogen- and sulfur-containing heterocycles. These heterocyclic compounds are mainly used in aroma compositions, exceptions are indoles and quinolines, which are important fragrance substances. 

Heterocyclic These are compounds having at least one hetero atom (any other atom but carbon, e.g. O, N and S) within the ring, and conforming to Hiickel s rule. The aromaticity of heterocyclic compounds, e.g. pyridine and pyrrole, can be explained as follows. 

Paal-Knorr synthesis It is a useful and straightforward method for the synthesis of five-membered heterocyclic compounds, e.g. pyrrole, furan and thiophene. However, necessary precursors, e.g. dicarbonyl compounds, are not readily available. Ammonia, primary amines, hydroxylamines or hydrazines are used as the nitrogen component for the synthesis of pyrrole. 

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