Nitrogen, heterocyclic compounds indole

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. 

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. 

The alkaloids are also relevant to drug design. Alkaloids are complex heterocyclic compounds that contain nitrogen and thus have base-like (hence the term alkaloid ) properties they are extremely structurally diverse. Nicotine is one of the simplest alkaloids. Oxidation of nicotine produces nicotinic acid, a vitamin that is incorporated into the important coenzyme nicotinamide adenine dinucleotide, commonly referred to as NAD" (oxidized form). The neurotransmitter serotonin is an alkaloid containing the aromatic indole ring system. 

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. 

Most of the heterocycles are known hy their trivial names, e.g. pyridine, indole, quinoline, thiophene and so on. However, there are some general rules to he followed in a heterocycle, especially in the use of suffixes to indicate the ring size, saturation or unsaturation as shown in the following table. For example, from the name, pyridine, where the suffix is -ine, one can understand that this heterocyclic compound contains nitrogen, has a six-memhered ring system and is unsaturated. 

The heterocyclization of peri-aminonaphthoyl compounds allows the preparation of three main types of benzo[crf]indole series, namely, bases 113, benzo[crf]indolium salts 114, and benzo[crf)indole-2-ones 115. Because closure to the nitrogen heterocycle is so facile, peri-amino-substituted naphthaldehydes and naphthyl ketones, even under conditions of their formation, are converted into benzo[crf]indoles 113. Those unsubstituted in position 2, as well as 2-alkyl-substituted benzo[cd]indoles 113 (R = H, Aik), have not been isolated because of their easy oxidation by air. 

Cyclization of a variety of alkylideneketenes generated by the Meldrum s acid method has provided a number of useful syntheses of nitrogen heterocycles. Thus, for example, FVP of 382 leads to the azepinone 383177, and the indole compounds 384 may give... 

The nitrogen in fuels consists of complex, mostly heterocyclic compounds. In petroleum crudes, these include pyrroles, indoles, isoquinolines, acridines, and porphyrins. During refining most of these concentrate in the heavy resin and asphaltene fractions, which might suggest their relatively late release in the... 

Nitrogen-containing heterocyclic compounds such as indoles and imidazoles are also formylated by the electron-rich olefin. 3-Methylimidazol-5-carboxaldehyde can be prepared from 2-methyl-imidazole (yield 83%) and 2-phenylindole-3-carboxaldehyde from 2-phenylindole (yield 64%). 

Heterocyclic compounds containing a nitrogen atom commonly undergo N-alkylation or C-alkylation. N-Methyl pyrrole can be prepared by interaction of methyl iodide with potassium pyrrole (40%). N-Carbethoxy pyrrole is made from chloroformic ester and potassium pyrrole. The C-alkylation of pyrroles has been discussed. 3-Alkylindoles are made by the alkylation and decarboxylation of indole-2-carboxylic acid. The conditions for alkylation of pyrrolidine are analogous to those employed for the alkylation of a secondary amine. Thus, pyrrolidine on treatment with n-butyl bromide and potassium hydroxide in boiling benzene is con-... 

In another study, ammonia fixation of N-labeled ammonium hydroxide with Suwannee River fiilvic acid, IHHS peat and leonardite humic acid were examined by solution NMR with the application of INEPT and DEPT pulse sequences.(23) Similar reaction of ammonia with all three samples is reported. Most of the nitrogen incorporated seems to be in the form of indole and pyrrole followed by pyridine, pyrazine, amide and aminohydroquinone nitrogen. The authors also suggest a possible reaction mechanism to explain the formation of the heterocyclic compounds identified in the spectra. They also claimed that these results need to be substantiated through further work with model compounds and experiments with the reaction conditions, i.e., in which phenols will undergo oxidation to quinones when reacted with ammonia. 

These compounds satisfy the criteria for aromaticity (planar, cyclic n system, and the Huckel number of 4n -I- 2 71 electrons) pyrrole, imidazole, indole, pyridine, 2-methylpyridine, pyrimidine, and purine. The systems with 6 7i electrons are pyrrole, imidazole, pyridine, 2-methylpyridine, and pyrimidine. The systems with 10 7i electrons are indole and purine. The other nitrogen heterocycles shown are not aromatic because they do not have cyclic 7i systems. 

Photocyclization of iV-chloroacetyl amines has been used previously in the synthesis of nitrogen heterocycles, and the reaction of the substituted amine (166) leads to a benzazepinone that can be elaborated to give pseudoprotopine alkaloids. Y-Chloroacetyl derivatives of the seven isomeric indolylethylamines give azepinoindoles and azocinoindoles by photocyclization. Quantum yields for the reaction are correlated with calculated (CNDO/2 and INDO) electron densities, and on this basis mechanisms are suggested the conclusion is that both indole radical cations and indolyl radicals (for the 1-substituted compounds) are... 

Zeolites are known to catalyze the formation of various nitrogen-containing aromatic ring systems. Examples include the synthesis of pyridines by dehydrogenation / condensation / cyclization of C -Cg precursors [1], the formation of methylpyridines by high-temperature isomerization of anilines [2], the amination of oxygen-containing heterocyclic compounds [3] and the Fischer indole synthesis [4,5]. The latter synthesis consists (see Scheme 1) of a condensation towards a phenylhydrazone followed by an acid-catalyzed cyclization with elimination of ammonia. The two reaction steps are usually combined in a one-pot procedure. 

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