Pyrrolo triazine ring

The synthesis of this ring system was achieved by the reaction of the ketene aminal 79 with 3-morpholino-l-ethyl-l,2,4-triazinium tetrafluoro-borate 78 to give 80 (89IZV494). Cyclization of 78 with the bifunctional nucleophile 81 gave the pyrrolo[3,2-e][l,2,4]triazinones 82 (88TL1431). This reaction represents the first example of orthocyclization onto the 1,2,4-triazine ring by the addition of dienophiles at C-5,6 (Scheme 20). 

Highly substituted pyrrolo[l,2- ][l,2,4]triazines were synthesized from pyrrole derivatives, by closure of the triazine ring. Thus, hydrolytic cleavage of some 1,2-diaminopyrroles having a 1-NH-BOC-protected amino function 43 followed by reaction with 1,2-dicarbonyl compounds afforded a one-pot access to the corresponding bicyclic heterocycles 44 (BOC = f-butoxycarbonyl Equation 6) < 1997J(P 1)1829>. 

Reaction of 1,2,4-triazinium salts with amides of acetoacetic acid results in 1,4,4a,5,7,7a-hexa-hydro-6/7-pyrrolo[3,2-e]-l,2,4-triazin-6-ones via the diaddition of bifunctional nucleophiles at the C-5 and C-6 positions of the 1,2,4-triazine ring (Equation (2)) <88TL1431>. 

Azinium cations undergo cycloaddition reactions with acetoacetamide to give the pyrrolo[3,2-e]-1,2,4-triazine ring system (Equation (12)) <89IZV438,89IZV1501). The reaction takes place under very mild conditions an ethanolic solution of the reactants is heated and then allowed to stand at room temperature for two days whereupon the desired fused heterocyclic product crystallizes. 

The destruction of heterocycles condensed to the 1,2,4-triazine ring can also be treated as a method of substituent modification. For example, the formation of 3-[acetoxy(phenyl)-methyl]-l,2,4-triazines 24 by treatment of [l,2,3]triazolo[5,l-c][l,2,4]triazines with acetic acid,340 and the degradation of the pyrimido[5,4-c]-1.2,4-triazines353 and pyrimido[4,5-e]-1,2,4-triazines to afford 25 and 26, respectively.331 354 Further reactions of this type are discussed in a previous review.8 For a synthesis of l,2,4-triazine-3,5,6-tricarboxylic acid from pyrrolo[2,l-c]benzo-l,2,4-triazine, see also Houben-Weyl, Vol. 4/1 b, p 643. 

The pyrrolo-[l,2-a]-j-triazine ring system, formed by viomycidine and ot,/S-diaminopropionic acid, explains the ultra-violet absorption of viomycin. This ring system may also be responsible for the antimicrobial activity of viomycin , because several dihydro- -triazines possess a remarkable activity towards many micro-organisms. Also this formula cannot yet explain all the results reported in the literature and the final structure for viomycin is thus still undetermined. 

In particular, it has been found that the reaction of 3-aryl-l,2,4-triazines 76, activated by acetic anhydride, with /3-aminovinyl ketones or /3-aminocrotonate 77 in acetic anhydride proceeds at room temperature very smoothly and regioselectively, leading to 3a,4,7,7a-tetrahydro derivatives 78 of the l//-pyrrolo[3,2-< ]-l,2,4-triazine ring system (Scheme 41) <2003RCB1740>. 

Two concurrent reactions, in which either the acetylenic fragment at C-3 of the 1,2,4-triazine ring participates in an intramolecular [4+2] Diels-Alder ring-transformation reaction ( = 1), or diethyl acetylenedicarboxylate undergoes an intermolecular 1,3-dipolar cycloaddition reaction, leading to pyrrolo[2,l ][l,2,4]-triazines, have been described (Scheme 112) <2001MC19>. 

Ring Syntheses Classified by Number of Ring Atoms in Each Component 11.14.8.1 Pyrrolo[1,2-b][1,2,4]triazine... 

Pyrrolo[l,2-rf [l,2,4]triazinones 21 were synthesized from methyl ester of /ra j-4-hydroxy-L-proline 72. The synthetic route involved formation of hydrazones followed by cyclisation with orthoesters <1998BMC349>. Similar reactions have been developed with 3-benzylindole-2-carbohydrazides 73 in reaction with triethyl orthoformate, giving the corresponding ring systems indolo[l,2-r][ 1,2,4]triazin-4-oncs 74 <2004JHC7>. 

A novel pyrido[l,2-6]pyrrolo[2,3-e]-a -triazine (19) is produced when compound (15) is treated with ammonia ammonia attacks the C-lOa carbon and causes ring opening to give the triazinium derivative (18 Nu = NH2) and the amine substituent is then able to react with the carbonyl group of the benzoyl substituent to give the cyclized product (19) in high yield. 

A new bicyclic betaine, a pyrrolo[l,2-.7 [l,2,4]triazin-2-ium -olate 1347, was prepared by the thermolysis of a ring-expansion reaction product 1346, 2,3-di(/-butyl)-l-hydroxy-2,3-dihydropyrrolo[l,2-.7 [l,2,4]triazin-4(17/)-one, of 1,2-di(/-butyl)-l,2-diaziran-3-one 1345 with 177-pyrrole-2-carbaldehyde (Scheme 256) <1995MI1>. Its cyclization reaction with a dipolarophile such as dimethyl 2-butynedioate leads to a fused ring-enlarged compound, a triazocinone derivative 1348 in rather low yield. Heating a solution of triazocine 1348 in benzene- 6 in an NMR tube at 140 °C for 0.5 h leads to its thermal transformation into compound 1349 in 21% yield via skeletal isomerization <1999T13703>. 

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