The Replacement Nomenclature System

At this point, we can introduce an entirely different system of nomenclature that is nevertheless accepted by lUPAC and is extremely valuable in multicyclic and bridged saturated systems. This is the replacement system, where the hydrocarbon name that would correspond to the entire ring structure, as if no heteroatom were present, is stated, and then given a Hantzsch-Widman prefix and number for the heteroatom(s). Thus, phenanthridine shown previously has the ring framework of the hydrocarbon phenanthrene, with N at position 5. The replacement name would be 5-azaphenanthrene. 

COMMON RING SYSTEMS AND THE NAMING OF HETEROCYCLIC COMPOUNDS 

This system also can be used for simpler ring systems. Thus, phos-phabenzene was the name first used when this compound initially was synthesized in 1971 by A. Ashe. The Hantzsch-Widman name would be the less informative phosphinine. 

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Further substitution of the peripheral carbon atoms of the cyclazines by heteroatoms (N, S, etc.) is indicated in this chapter according to the replacement nomenclature system (aza, thia, etc.). Although, strictly, this runs contrary to the rules,lc since it is a heterocyclic, not a hydrocarbon, system which is replaced, the connection between closely related compounds can more clearly be seen. It should be noted that Chemical Abstracts employs the systematic fusion nomenclature I, for instance, is pyrrolo[2,l,5-cd]indolizine. 

Several names have been used in the chemical literature for pyrrolo[l,2-a]pyridine including pyrrocoline, pyrindole, pyrrodine and 8-pyrrolopyridine, but the one which is now used by Chemical Abstracts, and which will be used in this chapter, is indolizine. The numbering of the system is shown in formula (1). The denomination of aza derivatives follows the replacement nomenclature system, e.g. 1-azaindolizine, etc. It should be noted that Chemical Abstracts follows the systematic fusion nomenclature 1-azaindolizine, for instance, is imidazo[l,2-a]pyridine. The cyclazine nomenclature is treated in Section 3.08.9.1. 

There are several types of nomenclature systems that are recognized. Which type to use is sometimes obvious from the nature of the compound. Substitutive nomenclature, in general, is preferred because of its broad applicability, but radicofunctional, additive, and replacement nomenclature systems are convenient in certain situations. 

The nomenclature of the family of compounds to be discussed below has for long been the cause of much confusion. The systematic name for a six-membered ring containing one sulfur atom is thiin, but Chemical Abstracts uses the name thiopyran, while many earlier publications have used the replacement nomenclature thiapyran (which is strictly inaccurate as thia implies replacement of carbon, rather than oxygen, by sulfur). Throughout this chapter the terms thiopyran and thiin will be used interchangeably, while thiadecalin nomenclature will be found convenient for the perhydrobenzothiopyran systems. 

Pyrimidine (1) is the trivial name for 1,3-diazine two me/a-oriented CH units in benzene have been replaced by nitrogen atoms. Quinazoline (2) is benzo-fused pyrimidine and is defined by the fusion nomenclature as benzo[if]pyrimidine, alternatively as 1,3-diazanaphthalene by the replacement nomenclature. Perimidine (3) is the trivial name for the pen -naphtho-fused pyrimidine system. It may be called (fusion names) l//-benzo[f/e]quinazoline or l//-naphtho[l,8-r/e]pyrimidine, or alternatively l//-l,3-diazaphenalene by the replacement nomenclature. However, the three trivial names are all system names accepted by lUPAC and approved as parents for further fusion name formation the benzo- and naphtho-pyrimidine names are therefore not used. In principle, additional rings can be fused onto the benzo or naphtho moiety in either quinazoline or perimidine without any profound alteration in heterocyclic reactivity. Aceperimidylene (4) and aceperimidine (5) are the trivial names for two cyclopenteno and cyclopentano fused perimidines. 

Figure 1. On the left, FR901483 structure with the replacement nomenclature numbering used in this review. On the right, FR901483 structure showing the heterocyclic system numbering (octahydro-1 //-7,1 Oa-inethanopyrrolo[ 1,2o]azocine) used by several authors.

An alternative nomenclature system for nucleotides emphasizes their acidic properties (a result of the phosphate group). The name of the base unit from the above nomenclature system forms the basis of the name. The ending -osine monophosphate or -ine monophosphate is replaced by -ylic acid. The prefix deoxy- is used as before to distinguish deoxyribose from ribose. 

The nomenclature of FA reflects the long history of their smdy and description. Most FA were originally described under trivial names prior to the adoption of the international molecular nomenclature rules in 1892 (Table 3.1). Even after adopting the International Union of Pure and Applied Chemistry (lUPAC) system for nomenclature (lUPAC-IUB, 1977), the habit of assigning trivial names to FA continues. The basis of the systematic nomenclature system is an extension of that accepted for hydrocarbon (alkane/alkene) naming. Hence, the descriptive name is based on the number of carbon atoms contained in the molecule, with the suffix -e replaced with -oic acid. However, in most instances, FA are referred to by their formula notations. As is the case with systematic and trivial names, there exists an lUPAC accepted formula notation nomenclature and several earher versions (Table 3.2). Each system... 

Organic ring systems are named by replacement nomenclature. Three- to ten-membered mono-cyclic ring systems containing uncharged boron atoms may be named by the specialist nomenclature for heterocyclic systems. Organic derivatives are named as outlined for substitutive nomenclature. The complexity of boron nomenclature precludes additional details the text by Rigaudy and Klesney should be consulted. 

There are 19, largely nonmetallic, elements encompassed by the Hantzsch-Widman system the prefixes to indicate them are shown in Table 2. These prefixes, all of which end in a (which may be lost by elision), are the same as those used in replacement nomenclature (Section 1.02.2.3). 

The fusion name l//-triazolo[4,5-d]pyrimidine for (140) is preferred by practitioners in the field and appears in CA indexes. On the other hand, the nonspecialist, who may well be uncertain about his command of fusion nomenclature, might more easily grasp the replacement name l//-l,2,3,4,6-pentaazaindene. (This is an appropriate place to emphasize that, by lUPAC rules, replacement names are to be based only on a completely carbocyclic parent. Notwithstanding the attractive simplicity of 8-azapurine for the example at hand, it has no sanction see, however. Section 1.02.3.2. The purpose of this avoidance is to forestall a multiplicity of names for systems containing several hetero atoms.)... 

If a tetrahedral center in a molecule has two identical substituents, it is referred to as prochiral since, if either of the like substituents is converted to a different group, the tetrahedral center then becomes chiral. Consider glycerol the central carbon of glycerol is prochiral since replacing either of the —CH9OH groups would make the central carbon chiral. Nomenclature for prochiral centers is based on the (R,S) system (in Chapter 3). To name the otherwise identical substituents of a prochiral center, imagine... 

Over the past two decades, the pharmaceutical community has become acutely aware that many substances of interest can be obtained in more than one crystal form, and that the properties of these solids may often be quite different. Polymorphism is the term used to denote crystal systems where a substance can exist in different crystal packing arrangements, but all of which are characterized by exactly the same elemental composition. Other crystal variations are known where a given substance exists in different crystal packing arrangements, but each of which exhibits a different elemental composition. Since this latter phenomenon usually involves the inclusion of one or more solvent molecules in the crystal, the term solvatomorphism has been coined to replace the inconsistent nomenclature used over the years. These and related phenomena have been the focus of several recent monographs [1-3],... 

Other minor systems are also in use. Some are traditional, and some are very restricted in their application. These include acid nomenclature (inorganic, for oxoacids and derivatives), replacement nomenclature (mainly organic, to denote replacement of skeletal atoms in a parent rather than replacement of hydrogen atoms — oxa-aza replacement is one variant), functional class nomenclature (this is again principally organic and involves the use of type names such as alcohol, acid and ether) and subtractive nomenclatures (such as organic-deoxy and inorganic-debor). These will all be referred to briefly as appropriate. 

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