Heterocycles pyridine reactions

The chemistry of these polycyclic heterocycles is just what you miglu expect from a knowledge of the simpler heterocycles pyridine and pyrrole Quinoline and isoquinoline both have basic, pyridine-like nitrogen atoms, anc both undergo electrophilic substitutions, although less easily than benzene Reaction occurs on the benzene ring rather than on the pyridine ring, and r mixture of substitution products is obtained. 

Aromatic N-containing heterocycles (pyridine, imidazole etc.,) and their alkyl derivatives represent an important group of products and they have received considerable attention because of their various applications. For instance, methyl pyridines (picolines) and dimethyl pyridines (lutidines) are a class of industrially valuable compounds for the production of dyes and fine chemicals [108]. Sreekumar et al [109] reported pyridine methylation to 3-picolines over Zni xCoxFe204 spinel systems at reaction temperature between 325 and 425°C. The... 

The displacement of halogen with a copper(I) acetylide and subsequent or synchronous copper catalyzed addition of a neighboring nucleophilic substituent to the triple bond (equation 2) constitutes a versatile synthesis of heterocycles. This reaction has been utilized both for the synthesis of furo[3,2-c]pyridines (equation 3) and furo[3,2-6]pyridines (equation 4) (68JHC227, 72MI31700>. 

Groebke, K., Weber, L. and Mehlin, E, Synthesis ofimidazo[l,2-a] annulated pyridines, pyrazines and pyrimidines by a novel three-component condensation, Synlett, 1998, 661 Blackburn, C., Guan, B., Shiosaki, K. and Tsai, S., Parallel synthesis of 3-aminoimidazo[l,2-a] pyridines and pyrazines by a new three-component condensation, Tetrahedron, 1998, 3635-3638 Bienayme, H. and Bouzid, K., A new heterocyclic multicomponent reaction for the combinatorial synthesis of fused 3-aminoimidazoles, Angew. Chem., Int. Ed. Engl, 1998, 37, 2234-2237. 

The most reactive in this reaction were N-phosphorylated salts of isoquinoline, which hetarylated indole even at room temperature. Pyridine and particularly quinoline are less reactive. With these heterocycles the reaction took place only in the presence of the more active dialkylphosphinic acid chlorides. The steric effects of the substituents at the phosphorus atom have a definite role. It was found that substituents with smaller molecular mass and less branched substituents made it possible to conduct the reaction under milder conditions and lead to an... 

N-Heterocyclics. The reaction of primary amines with the carbonyl products derived from lipid oxidation is a major pathway in lipid-protein interactions. Formation of Schiff s base intermediates followed by cyclization and rearrangement can yield imines, pyridines and pyrroles (5,15,30,31). For example, 2-pentylpyridine may result from the reaction of ammonia with 2,4-decadienal, one of the principle aldehydes from the autoxidation of linoleate (5). 

Radical nucleophile oxidation based on one-electron oxidation, known as the Minisci reaction, is employed for the functionalization of /V-heterocycles with acidic hydrogen peroxide in the presence of iron(II) salts (Figure 3.112).472 A range of A-heterocycles (pyridines, pyrazines, quinolines, etc.) which are activated towards attack by nucleophilic radicals when protonated are suited to this chemistry. The Minisci reaction is suitable for the preparation of carboxylic amides (from formamide), carboxylic esters (from pyruvic esters via a hydroxyhydroperoxide), aldehydes (from 1,3,5-trioxane) and alkylated pyridines (either from carboxylic acids or from alkyl iodides in dimethyl sulfoxide).473 The latter reaction uses dimethyl sulfoxide as the source of methyl radical (Figure 3.112). 

Copper(I) acetylides provide a useful route to the synthesis of a variety of organic acetylenic compounds and heterocycles, by reaction with aryl and other halides. A particularly important indirect use, where acetylides are probable intermediates, is the oxidative dimerization of acetylenes. A common procedure is to use the N, N,N, TV -tetramethylethylenediamine complex of CuCl in a solvent, or CuCl in pyridine-methanol, and oxygen as a reoxidant for Cu+ ... 

Representative examples of Pd-catalyzed heterocycle carbonylation reactions are shown below. Alkoxycarbonylation of 2,3-dichloro-5-(methoxymethyl)pyridine (79) took place regioselectively at C(2) to give ester 80 [79]. Aminocarbonylation of 2,5-dibromo-3-methylpyridine also proceeded preferentially at C(2) to give amide 81 despite the steric hindrance of the 3-methyl group [80]. 

This chapter describes in general terms the types of reactivity found in the typical six- and five-membered aromatic heterocycles. We discuss electrophilic addition (to nitrogen) and electrophilic, nucleophilic and radical substitution chemistry. This chapter also has discussion of orf/to-quinodimethanes, in the heterocyclic context. Organometallic derivatives of heterocycles, and transition metal (especially palladium)-catalysed chemistry of heterocycles, are so important that we deal with these aspects separately, in Chapter 4. Emphasis on the typical chemistry of individual heterocyclic systems is to be found in the summary chapters (7, 10, 13, 15, 19 and 23), and a more detailed examination of typical heterocyclic reactivity and many more examples for particular heterocyclic systems are to be found in the chapters - Pyridines Reactions and Synthesis , etc. 

Anderson and Webster (10) showed the pyridyl-silicon bond of 2-(trimethylsilyl)pyridine to be susceptible to cleavage by alcohol and water to form unsubstituted pyridine. Thames and coworkers (11) showed that neutral reagents, including aldehydes, acid halides, chloroformates, and anhydrides, have the ability to cleave several silicon-carbon bonds on select heterocycles (Schemes VI-VIII). However, the silicon-carbon bond of nonheterocycles is not susceptible to neutral reagent cleavage, and too, the full extent of heterocyclic cleavage reactions is not known. 

For a brief discussion of substitution reactions on pyridines, sec Eichcr, T., Hauptmann, S. The Chemistry of Heterocycles Structures, Reactions. Synthesis, and Applications, 2nd ed. Wiley-VCH Weinheim, Germany, 2003 pp 269-310. For a more comprehensive discussion, sec Comins, D. L., Joseph, S. P. Pyridines and their Benzo Derivatives Reactivity at the Ring. In Comprehensive heterocyclic Chemistry H Katrizky, A. R. Rees, C. W. Scriven, E. F. McKillop, A. Eds. Pergamon Oxford, 1996 Vol. 5, p 37. 

The required pyridinium salts can be obtained by the King-Ortoleva reaction (see p 273), as is shown by the synthesis of benzothiazole-2-carbaldehyde 237. In the Krohnke reaction, the heterocycle pyridine ensures the targeted conversion CH3 -> CH=0 of methyl groups in arenes or heteroarenes [78]. 

Recent progress in the synthesis of heterocycles (pyridines, p3ridones, pyrans, pyrimidinediones, etc.) using [2 + 2 + 2] cycloaddition reactions catalyzed by transition metal complexes 06ASC2307. 

Small hydrogen isotope effects have been found in a nucleophilic substitution of an aromatic heterocycle, the reaction of cyanuric chloride with aniline-N,N-d2 in benzene solution (Zollinger, 1961a). As the effects are small (5%), it is difficult to draw definite mechanistic conclusions. The reactions of cyanuric chloride and other halogenated triazine derivatives are subject to bifunctional catalysis (e.g. by carboxylic acids and by a -pyridone) and to catalysis by monofunctional bases like pyridine (Bitter and Zollinger, 1961). Reinheimer et al. (1962) measured the solvent isotope effect in the hydrolysis of 2-chloro-5-nitro-pyridine (A h,o/ d.o = 2 36). The result makes it probable, but... 

Katritzky, A., Barcock, R., Siskin, M., et al. (1994). Aqueous high-temperature chemistry of carbo- and heterocycles. 23. reactions of pyridine analogs and benzopyrroles in supercritical water at 460°C, Energy Fuels, 8, pp. 990-1001. 

Photochemical properties of azido derivatives of six-member aza-heterocycles (pyridine, pyrimidine, triazine, quinoline, acridine) are discussed. Data on the stmcture of the reaction products formed under photolysis of azides in different conditions (solvent, temperature, additives), and also data on the matrix isolation spectroscopy of heterocyclic nitrenes, including high-spin nitrenes, produced by low-temperature photolysis of the corresponding azides are shortly examined. 

Alkoxythiazoles are prepared by heterocyclization (274, 462). The Williamson method using catalytic amounts of KI and cupric oxide is also possible (278. 288, 306). 5-Acetoxy-4-alkenylthiazoles are obtained by treatment of 242 with acetyl chloride and triethylamine or with acetic anhydride and pyridine (450). Similarly, the reaction of diphenylketene with 242 affords 5-acyloxy-4-alkenylthiazoles (243) (Scheme 120) (450). The readiness of these o-acetylations suggests that 4-alkylidene thiazoline-5-one might be in equilibrium with 4-alkenyl-5-hydroxythiazoles (450). 

Although acetonitrile is one of the more stable nitriles, it undergoes typical nitrile reactions and is used to produce many types of nitrogen-containing compounds, eg, amides (15), amines (16,17) higher molecular weight mono- and dinitriles (18,19) halogenated nitriles (20) ketones (21) isocyanates (22) heterocycles, eg, pyridines (23), and imidazolines (24). It can be trimerized to. f-trimethyltriazine (25) and has been telomerized with ethylene (26) and copolymerized with a-epoxides (27). 

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