Pyrazine naming

Examination of the pyrazino[2,3-rf]pyrimidine structure of pteridines reveals two principal pathways for the synthesis of this ring system, namely fusion of a pyrazine ring to a pyrimidine derivative, and annelation of a pyrimidine ring to a suitably substituted pyrazine derivative (equation 76). Since pyrimidines are more easily accessible the former pathway is of major importance. Less important methods include degradations of more complex substances and ring transformations of structurally related bicyclic nitrogen heterocycles. 

The Creutz-Taube compound (named after its discoverers), [(NH3)5Ru(pyrazine)Ru(NH3)5]5+ is the middle member of a redox-related series, formally containing one ruthenium(II) and one ruthenium(III) (Figure 1.14) the interest lying in whether the two ruthenium centres are identical, whether the valencies are trapped or whether there is partial delocalization. 

Azirines are dimerized under various conditions to dihydropyrazines or their dehydrogenated products, namely pyrazines (Section 8.03.9.5). Quinoxalines are oxidized with potassium permanganate to afford 2,3-pyrazinedicarboxylic acids, and pteridines are hydrolyzed to give 3-amino-2-pyrazinecarboxylic acid derivatives. Condensation of 3,4-diamino-l,2,5-thiadiazole 176 with a-diketones produces l,2,5-thiadiazolo[3,4- Jpyrazines 177, which are reduced to provide 2,3-diaminopyrazines 178 (Scheme 51) <1997JCM250>. 

There are two theories as to the mechanism of the formation of imidazole and pyrazine compounds, namely, (a) the prior formation of glycosylamines and aminodeoxy sugars, and (b) the fragmentation mechanism. 

Not listed and therefore not permitted are substances from chemical groups like pyrazines, pyridines, amines, amides, or aliphatic lower alcohols, aldehydes and hydrocarbons (C5 and lower) if not mentioned by individual name [17]. 

The effect of the various substituents in the 2-position of pteridine has been investigated.24 Here the (—1) substituents, which disfavour hydration of the 3,4-position, do not interfere with its occurrence in the alternative site for the pteridine nucleus, namely in the pyrazine ring. 

Chemical Name 1-Piperazinecarboxylic acid, 4-methyl-, 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester... 

Recently, two pyrazine (pz)-linked hetero-triads of cobalt phthalocyanine (CoPc) and ZnTPP, namely (CoPc)-pz-(ZnTPP)-pz-(CoPc) (15) and (ZnTPP)-pz-(CoPc)-pz-(ZnTPP) (16), have been prepared [30], The thermal properties of these triads and related macrocyclic components have been studied by thermal gravimetric analysis and differential scanning calorimetry. It has been found that the thermal stability of axial coordination increases in the order ZnPc(pz)2 < ZnTPP(pz)2 sa CoPc(pz)2, and the thermal decomposition of the triads 15 and 16 proceeds firstly via the degradation of the spacer ligand. 

The aspergillic acids are an important group of naturally occurring pyrazine derivatives. They are formed by cultures of the Aspergillus species and were the first natural products shown to be cyclic hydrox-amic acids.9 Aspergillic acid itself was isolated10 in 1943 from A.flavus and subsequently shown to have structure 3. An isomer of deoxy-aspergillic acid, also isolated from A. flavus, was shown to be 3,6-diisobutyl-2-pyrazinone (4) and named flavacol.11... 

Thirteen diazinodiazines without bridged heteroatom are theoretically possible. All of these have been reported in the literature. There are (i) four pyridazinopyridazines, namely pyridazino-[4,3-c]pyridazine (A), pyridazino[3,4-c]pyridazine (B), pyridazino[4,5-c]pyridazine (C), and pyridazino[4,5-[Pg.738]

Aromatic sextets are not essential for the stability of heterocyclic rings and saturated and partially-saturated rings occur widely. These are usually named as the corresponding dihydro or tetrahydro derivatives, e.g., 37-39. The fully-saturated derivatives of pyridine and pyrazine are commonly referred to as piperidine 40 and piperazine 41. The antihypertensive calcium channel antagonist nifedipine 42 is a 1,4-dihydropyridine derivative , and sildenafil 43, which contains a piperazine ring, is a phosphodiesterase inhibitor used to treat erectile dysfunction . 

An odor can be described by the combination of threshold value and odor quality. The threshold value, the lowest concentration that creates an odor impression, can be considered the intensity factor, whereas the odor quality describes the character of the aroma. As has been mentioned under olfactory theories, attempts at reducing the number of characteristic odor qualities to a small number have not been successful. In many cases, the aroma and flavor of a food can be related to the presence of one or a few compounds that create an impression of a particular food when smelled alone. Such compounds have been named contributory flavor compounds by Jennings and Sevenants (1964). Some such compounds are the pyrazines, which give the odor quality of green bell peppers nootkatone for grapefmit esters for fruits ... 

The general term oxypyrazine is used here to include derivatives such as the cy-cloamidic tautomeric pyrazinones (1), the alcoholic hydroxyalkylpyrazines (2), the etherial alkoxypyrazines (3-5), the cycloamidic nontautomeric pyrazinones (6), and pyrazine A-oxides (7, 8) in addition, related types like diketopiperazines, acy-loxypyrazines, pyrazine quinones, and endoperoxypyrazines are covered as appropriate. Some brief ancillary information on trivial names, natural occurrence, and biological activities of pyrazines (mainly oxy derivatives) is collected in a final Appendix section. 

Because most pharmaceutical, agrochemical, and naturally occurring pyrazines are in fact oxypyrazines of one sort or another,12181281 an alphabetical list of many such recently mentioned pyrazines (under their trivial names, if any) is presented at this point. Each entry includes a chemical name or indication of structure, the type of bioactivity and/or natural source (as appropriate), and the CAS Registrary number and/or leading reference(s) (to facilitate any search for detailed information). 

Since the excellent 1973 summary of azido—tetrazolo valence-tautomerism in nitrogenous heterocycles,1713 little has been added to our knowledge of factors governing such tautomerism (227 228) in the pyrazine series. However, it has been shown by NMR studies that 2-azidopyrazine 4-oxide (229) exists as such in chloroform, as tetrazolo[l,5-a]pyrazine 7-oxide (230) in dimethyl sulfoxide, and as a mixture in acetone.272 For obvious pragmatic reasons, all such compounds are named as azidopyrazines in this book, irrespective of their predominant structures. 

Nearly 1000 compounds have so far been identified in the volatile constituents of meat from beef, chicken, mutton and pork (6). The largest number of volatiles has been determined in beef and these were representative of most classes of organic compounds. Hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids, esters, lactones, ethers, sulfur and halogenated compounds as well as different classes of heterocyclic substances (Figure 1) namely furans, pyrldlnes, pyrazines, pyrroles, oxazol(in)es, thiazol(in)es, thiophenes were present in cooked meat flavor volatiles as shown in Table I. Many of these compounds are unimportant to the flavor of meat and some may have been artifacts (16). 

During the isolation of cathinone, 3,6-dimethyl-2,5-diphenyl pyrazine (3) was also found (14). This is doubtless an artifact, the product of oxidative dimerization of cathinone which involves the formation of condensation product 4 as an intermediate (18). Also found was the diketone (5) and the cinnamoyl compound (6) (14), later shown to have the (S) stereochemistry illustrated and named merucathinone (6,19,20). Merucathine (7) has also been isolated (6,21,22), and this and merucathinone are minor components. (-)-Norephedrine (8) also occurs in khat (14), and its iV-formyl derivative (9) has been found in plant material of South Arabian origin (23). Despite earlier positive reports, ephedrine and pseudoephedrine have not been verified as components of khat (14). HPLC has been employed to separate and quantify mixtures of the khatamines cathinone, (+)-norpseudoephedrine, and (—)-norephedrine in connection with a study of their distribution in different parts of the khat plant and in specimens of different geographical origin (20,21). 

TABLE 1.1 NAMES ASSIGNED TO SOME SIMPLE PYRAZINES BY EARLY WORKERS... 

Diphenylpyrazine (1, R = R = Hi, R = R = H) was the second pyrazine synthesized, and it was prepared by Staedel and Riigheimer (10) in 1876 by the action of ammonia on w-chloroacetophenone and was named isoindol. These authors postulated the first structure for a pyrazine as an inner anhydride (2) of an amino ketone. 

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