Heterocyclic compounds, aromatic indoles

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as useful starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, and 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-aromatics (mainly pyrroles and indoles) and saturated nitrogen heterocycles such as pyrrolidines and their derivatives. 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

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. 

Other commonly occurring chemical groups in essential oils include aromatics such as /3-phenethyl alcohol, eugenol, vanillin, benzaldehyde, cinnamaldehyde, etc heterocyclics such as indole, pyrazines, t hi azoles, etc hydrocarbons (linear, branched, saturated, or unsaturated) oxygenated compounds such as alcohols, acids, aldehydes, ketones, ethers and macrocyclic compounds such as the macrocyclic musks, which can be both saturated and unsaturated,... 

Ultraviolet absorption spectra have been used for many years in a qualitative way to indicate similarities in the bonding patterns of different compounds. The recorded UV spectra of azoloazines are characterized by a band at 250-280 nm which is ascribed to a n-n transition and which finds similarity in indole as well as other aromatic carbocyclic and heterocyclic compounds (84CHEC-1(4)497). 

The synthesis has been applied to a great variety of Mannich bases derived from aromatic compounds and from heterocycles, such as indole, pyridine, quinoline, coumar-in, etc.104 Compound 198, for instance, yields the pyranopyridine shown in equation 84104. 

The PNA fraction of the shale oil was smaller (6%) than that fraction in the coal liquids (10- 29%). In shale oil, a larger fraction of the PNA compounds are alkylated than in coal-derived liquids. For example, C5 or higher-substituted aromatics were seen in shale oil but C3 substitution was rare in coal liquid. This characteristic difference in alkyl substitution was repeated also when the N-heterocyclic compounds were similarly compared. Few alkylated species were seen in the coal liquids but Ce and higher-substituted pyridines, quinolines, acridines, indoles, and carbazoles were detected in shale oil. For example, the PNA fraction of shale oil contained many indoles which can be seen in the gas chromatogram of this fraction see Figure 7). The different alkyl substitution patterns found in these two syncrude materials may well reflect the underlying structural differences in coal and kerogen. 

In the Reimer-Tiemann reaction, aromatic rings are formylated by reaction with chloroform and hydroxide ion." ° The method is useful only for phenols and certain heterocyclic compounds such as pyrroles and indoles. Unlike the previous formyla-tion methods (11-18), this one is conducted in basic solution. Yields are generally... 

The ASE values correlate with magnetic susceptibility for the five-membered heteroaromatic compounds. Magnetic and polarizability criteria put the order of aromaticity as thiophene > pyrrole > furan. The other criteria of aromaticity discussed in Section 8.2 are also applicable to heterocyclic compounds. HOMO-LUMO gaps and Fukui functions (see Topic 1.5) have been calculated for compounds such as indole, benzofuran, and benzothiophene and are in accord with the known reactivity patterns of these heterocycles. 

Quinoline, indole, imidazole, purine, and pyrimidine are other examples of heterocyclic aromatic compounds. The heterocyclic compounds discussed in this section are examined in greater detail in Chapter 21. 

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. 

Heterocyclic aromatics with a prominent N-H band include pyrrole and indole where the nitrogen is attached to a single hydrogen. For these compounds, the strong first overtone N-H is apparent at 6835 cm (1463 nm), and the combination band is observed at 4715 cm i (2121 nm). The N-H overtone can be shifted by as many as 400 cm when other substituents are present, such as in 2,2-dimethyl-thiazolidine, where the band is observed near 6450 cm i (1550 nm). When N-H is present in the heterocyclic compound, a second-overtone bending band may be observed as a very weak shoulder near the 4715-cm (2121-nm) position. Other differences between het-erocyclics are found in the C-H region between 6300 cm and 5700 cm i (1587 nm to 1754 nm). 

Other kinds of molecules besides benzene-like compounds can also be aromatic. The cyclopentadienyl anion and cycloheptatrienyl cation, for instance, are aromatic ions. Pyridine and pyrimidine are srx-memhered, nitrogen-containing, aromatic heterocycles. Pyrrole and imidazole are five-membered, nitrogen-containing heterocycles. Naphthalene, quinoline, indole, and many others are polycyclic aromatic compounds. 

Volatile components constitute about 0.1% of roasted coffee by weight Cojfea species, Rubiaceae), and more than 200 substances have been shown in green coffee. More than 800 compounds are known to make up the aroma of roasted coffee. Of these, only about 60 compounds have a significant role in the coffee aroma. Especially typical are a large number of heterocyclic compounds, mainly furans, pyrroles, indoles, pyridines, quinolines, pyrazines, quinoxalines, thiophenes, thiazoles and oxazoles, which arise in caramehsation and the MaiUard reaction during coffee roasting. In addition to heterocyclic products, other important volatiles are also some aliphatic compounds (hydrocarbons, alcohols, carbonyl compounds, carboxylic acids, esters, aliphatic sulfur and nitrogen compounds), alicyclic compounds (especially ketones) and aromatic compounds (hydrocarbons, alcohols, phenols, carbonyl compounds and esters). 

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