Pyrrocolines

A number of other syntheses of coniine have been effected, of which that of Diels and Alder is of special interest. The initial adduct of pyridine and methyl acetylenedicarboxylate, viz., tetraraethylquinolizine-1 2 3 4-tetracarboxylate (IX) on oxidation with dilute nitric acid is converted into methyl indolizinetricarboxylate (X). This, on hydrolysis and decarboxylation, furnishes indolizine, the octahydro-derivative (XI) of which, also known as octahydropyrrocoline, is converted by the cyanogen bromide method (as applied by Winterfeld and Holschneider to lupinane, p. 123) successively into the broraocyanoamide (XII), cyanoaraide (XIII) and dZ-coniine (XIV). A synthesis of the alkaloid, starting from indolizine (pyrrocoline) is described by Ochiai and Tsuda. ... 

Pyridine, and its monomethyl and 3,5-dimethyl derivatives " combine exothermically with dimethyl acetylenedicarboxylate in ether yielding some ether soluble materials, including trimethyl pyrrocoline-1,2,3-tricarboxylate (Section III,F,3) and deep red ether-insoluble gums. A number of crystalline compounds have been isolated from these gums by fractional crystallizations and will now be considered in detail. In the case of pyridine, Diels et al. ° isolated a red labile 1 2 molar adduct, which they formulated as (75), which isomerized rapidly on standing to a yellow stable adduct (76). These formulations are no longer accepted. Diels and Alder also suggested that the acetylenic ester first dimerized to the diradical (74) which then combined with the pyridine. 

N-Heteroaromatic compounds like pyridine, pyridazine, pyrazine, isoquinoline, and their derivatives42,250 react with diphenyl cyclopropenone in a formal (3+2) cycloaddition mode to the C=N bond of the heterocycle. As expected from the results discussed earlier (p. 67), the reaction is initiated by attack of nitrogen at the cyclopropenone C3 position and followed by stabilization of the intermediate betaine 390 through nucleophilic interaction of the Cl/C3 bond with the activated a-site of the heterocycle, giving rise to derivatives of 2-hydroxy pyrrocoline 391—394). In some cases, e.g. diphenyl cyclopropenone and pyridine42, further interaction with a second cyclopropenone molecule is possible under the basic conditions leading to esters of type 392. 

In indole s isomer pyrrocoline (l-azabicyclo[4,3,0]nonatetraene) catalytic hydrogenation over palladium in acidic medium reduced the pyrrole ring [466, in neutral medium the pyridine ring [467],... 

Robinson and Sugasawa (8) selected dibenzo[b,g]pyrrocoline for the parent ring system, and this name was adopted for the alkaloid family. The numbering is shown on structure 3 although Robinson used a different pattern. The systematic name for the ring system is indolo[2,l-a]isoquinoline, but di-benzo[ib,g]indolizine also appears in the literature. 

The benzo[a] (19), benzo[/t (15) and benzo[c] (16) fused heterocycles are heterocyclic analogues of naphthalene, with the dibenzo heterocycles (17) bearing a similar electronic relationship to phenanthrene. Some of these compounds are still known by their trivial names indole (15 Z = NH), isoindole (16 Z = NH), carbazole (18) and indolizine (19). The names thianaphthene and pyrrocoline for (15 Z = S) and (19) respectively are now little used. Particular confusion can arise in consulting... 

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. 

This already has several names (see Patterson and Capell, p 116, compd 712), such as Pyrido-2,1—C -s-triazole, Triazole-pyridine, 2 3-Diazo-pyrrocoline, Benztriazole and 1,23-Benzisotri-azole. Of these, only the first name is really scientific and would allow for writing the formula, once one leams what the letter C signifies. This system, however, not only uses numerals for positions, but also introduces letters, a,b,c,d,e, etc, for each side of a ring compd. This, in our opinion, is an unnecessary complication... 

Here the hypothetical 2,N (or 2,2) attack produces a five-membered ring. The tetracyclic product is treated here as an isoquinoline, but it can also be seen as a disubstituted dihydroindole. The usual chemical classification is that of a substituted pyrrocoline, the name for the heterocycle that is the middle two rings of this system. 

Indolizine (pyrrocoline). Indolizine109,110 and its 2-methyl (eq. 12.57), 3-methyl, and 2,3-dimethyl derivatives110 were hydrogenated to the corresponding indolizidines (octahydropyrrocolines) over platinum oxide in acetic acid. Indolizine was also hydrogenated to indolizidine over prereduced platinum oxide in ethanol and a drop of hydrochloric acid.111... 

C. C. J. Culvenor, Current Trends Heterocyclic Chem., Proc. Symp., Canberra, 1957 pp. 103-109. Academic Press, New York, 1958. Indolizine (pyrido[l,2-a]pyrrole, pyrrocoline) and hydro derivatives N. Campbell, In The Chemistry of Carbon Compounds (E. H. 

Indolizine (pyrrocoline, pyrido[l,2-a]pyrrole) and hydro derivatives see Section IV, A, 1,6. 

Indolizine (Pyrrocoline) werden in der Regel mit Platin(IV)-oxid in sauremMedium-19-24 Oder mit Raney-Nickel unter Druck25,26 zu den Octahydro-Verbindungen hy-... 

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