Compounds that Contain Three Heteroatoms

A subcategory of dopamine receptor antagonists has found some use as antiemetic agents administered in conjunction with antimmor chemotherapy. The preparation of one of these agents based on a benzotriazole nucleus begins with nitration of the amino salicylate ester (67-1). Catalytic hydrogenation of the product (67-2) leads to the orf/zo-diamine (67-3). Treatment of this last product with nitrous acid 

FIVE-MEMBERED HETEROCYCLES FUSED TO A BENZENE RING 

Patent 5,854,282. Note this patent describes the chemistry up to the phenol 2-8. The alkylation step is conjectural though well precedented. 

Lombardino, J. G. in Nonsteroidal Antiinflamatory Drugs, Ix)mbardino, J. G., ed., Wiley-Interscience, New York, 1985, 261. 

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Sulfur containing heterocycles are also common Compounds m which sulfur is the heteroatom m three four five and six membered rings as well as larger rings are all well known Two interesting heterocyclic compounds that contain sulfur-sulfur bonds are hpoic acid and lenthiomne... 

In using the tables, it would be best to survey the list of tables included in each chapter to determine how many categories might possibly contain the compound of interest. It should be noted that a large number of cyclophanes which contain fewer than three heteroatoms are not included in this book since they are not generally useful as cation binders. 

McKay and Latham (1981) have also determined compound class distributions in the high-boiling distillates and the residua for four crude oils. As shown in Table VIII, the content of heteroatom compounds increases with increasing boiling point. The 675°C+ residuum may have nearly 10 times the acids, bases, or neutral Lewis (pyrrolic and amides unreactive to column resins) bases compared to the VGO portion (370-535°C). Grizzle et al. (1981) have also employed compound class separations and have observed similar trends. McKay and Latham (1981) calculated that each acid, base, or neutral nitrogen molecule in the <675°C residuum contains three to five heteroatoms. 

Though you have only seen a couple of examples of the latter, it is clear that organosulfur and organoselenium chemistry are closely related. In the next chapter we will look at the quite different type of chemistry exhibited by organic compounds containing three other heteroatoms—silicon, tin, and boron. 

Benzene is the archetypal example of a compound that displays aromatic properties. Aromatic compounds are characterised by a special stability over and above that which would be expected as a result of the delocalisation of the double bonds in a linear system. Typically, this extra stability is associated with the closed loop of six electrons, the aromatic sextet, as occurs in benzene itself. However, larger and smaller loops are possible. So long as there are (4n+2)7i electrons (where n is an integer from zero, upwards) present in (at least three) adjacent p sub-orbitals that form a closed circuit, then the resultant molecule will be aromatic. It is also possible for heteroatoms to form part of the cyclic structure, and for the structure to be charged. Furthermore, aromatic compounds, in contrast to unsaturated compounds, tend to undergo substitution reactions more readily than addition reactions. This is because it is usually thermodynamically favourable to preserve the aromatic stability rather than release the energy contained in the double bonds. 

Another important type of complex is formed between metal ions and cyclic organic compounds, known as macrocycles. These molecules contain nine or more atoms in the cycle and include at least three heteroatoms, usually oxygen, nitrogen, or sulfur. Crown ethers such as 18-crown-6 and dibenzo-18-crown-6 are examples of organic macrocycles. Some macrocyclic compounds form three-dimensional cavities that can just accommodate appropriately sized metal ions. Ligands known as cryptands are examples. Selectivity occurs to a large extent because of the size and shape of the cycle or cavity relative to that of the metal, although the nature of the heteroatoms and their electron densities, the compatibility of the donor atoms with the metal, and several other factors also play important roles. 

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