1.2.4- Triazinium salts, reaction

Pyrrolo[ 1,2-b [l, 2,4[triazinium salt 30 was obtained (90CB2039) by the reaction of hydrazone 29 with the Vilsmeier reagent prepared from DMF and oxalylchloride (Scheme 9). 

It was shown that ring-opening reaction of the pyrido[l,2-A [l,2,4]triazinium salt 97 may easily occur with pyrrolidine to afford cis-trans and/or trans-trans triazinyl dienes 98 and 99 98 could be isomerized to -trans-i-trans isomer 99 (Equations 7 and 8) <1996JOC4423, 2001CPH(266)77>. 

The arylfuro-fused pyrido[l,2-/ ][l,2,4]triazinium salt 179 undergoes reaction with methyl hydrazine to give the zwitterionic pyrido-fused pyridazino[3,4- ][l,2,4]triazine 31 as shown in Scheme 32 <2003ARK62, 1997CC757>. Nucleophilic attack of the hydrazine at the bridgehead results in the elimination of an enol that then allows ring closure via attack of the other hydrazine nitrogen onto the carbonyl of the keto tautomer. 

It was hoped that ring contraction of the triazinium salt 166 would give imidazo[2,l-6]thiazolium salts (167) on treatment with acid, but instead the free base of 166 was isolated on work-up of the reaction.159 Related pyridotriazine hydrobromides 168 underwent contraction in acid to give imidazopyridinium salts. 

The unexpected formation of the blue crystalline radical cation (97) from the reaction of triazinium salt (98) with tetracyanoethylene has been reported and the product identified by its EPR spectrum and by X-ray crystallography (Scheme 42).199 Carboxylic acids react with the photochemically produced excited state of N-t-a-phenynitrone (PBN) to furnish acyloxy spin adducts RCOOPBN. The reaction was assumed to proceed via ET oxidation of PBN to give the PBN radical cation followed by reaction with RCO2H.200 The mechanism of the protodiazoniation of 4-nitrobenzenediazonium fluoroborate to nitrobenzene in DMF has been studied.201 Trapping experiments were consistent with kinetic isotope effects calculated for the DMF radical cation. The effect of the coupling of radicals with different sulfur radical cations in diazadithiafulvalenes has been investigated.202... 

In fact, all other reactions of azinium cations with various 1,3- and 1,4-binucleo-philes represent AN AN processes resulting in the formation of stable di-aH-adducts, for example 218 or 220 (Scheme 64). Thorough investigations of these adducts, mostly derived from quinoxalinium and 1,2,4-triazinium salts, were carried out by Chupakhin and Charushin (for review see (88AHC(43)301, 04PAC1621)). They established that the di-adducts 218 and 220 have the corresponding mono-adducts 217 and 219 as their precursors. All mono- and di-adducts interconvert and depending on conditions any of them can be isolated. 

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>. 

Pyrido[l,2-7][l,2,4]triazinium salts 113 can be obtained from 112 with benzil in the presence of either base <2001CPH77> or sulfuric acid (Scheme 73) <2003ARK(xiv)155>. In an analogous reaction, 1,2-diaminopyridines 114 are transformed into 2,3,6-trioxopyridotriazines 115 by treatment with oxalyl chloride in the presence of triethylamine (Scheme 74) <1998SC3331, CHEC-III(12.03.2A4)237>. 

Synthesis of IV-monosubstituted 1,2,3-triazinium salts 13, from 1,2,3-triazines 12, and their reaction towards C-nucleophiles have been described <038413>. 

Amer, M. I., Booth, B. L., Noori, G. F. M., Proenca, M. F. J. R. P. The chemistry of nitrilium salts. Part 3. The importance of triazinium salts in Houben-Hoesch reactions catalyzed by trifluoromethanesulfonic acid. J. Chem. Soc., Pet1[Pg.605]

Quaternary N-alkyl-1,2,4-triazinium salts are undoubtedly more reactive toward nucleophilic reagents than uncharged 1,2,4-triazines and are, therefore, attractive substrates. Only a few reports on the synthesis and reactions of N-alkyl-1,2,4-triazinium cations have been published (71CC1636 78HC(33)189 84LA283 86KGS1535 88KGS525). 

Another example of interaction between A7/-triazinium salts and C-nucleophiles is the reaction of 3-substituted 1,2,4-triazines with indoles in the presence of trifluoroacetic acid (Scheme 17) (87MI2 88MI1). 

By contrast, when comparing the relative reactivity of the C-3 and C-6 positions in 3,6-dichloro-5-amino-l,2,4-triazine (95) with sodium meth-oxide, a different reaction pattern was observed. Substitution takes place at C-6 and not at C-3, yielding 5-amino-3-chloro-6-methoxy-l,2,4-triazine (96). When the reaction is carried out in methanol in the presence of hydrochloric acid, C-3 substitution is observed, yielding 5-amino-6-chloro-3-methoxy-l,2,4-triazine (97) (Scheme 59) (75CCC2680). In this case we deal with N2H- and A -triazinium salts stabilized by conjugation with the amino group. In these azinium salts the electrophilicity at C-3 is likely more enhanced than at C-6. 

Reaction of alkali hydroxide with l-methyl-l,2,4-triazinium salts 149 provokes transformation into 1,2,4-triazole derivatives 153 (Scheme 85) (71CC1636). The reaction is presumed to be initiated by addition of the nucleophile on the carbon adjacent to the quaternary nitrogen (i.e., at C-6). Attempts to obtain spectroscopic evidence for the intermediary cr-ad-duct 150 failed however, some support for their formation is provided by the fact that 1-methyl-1,2,4-triazin-6-ones 152 were isolated as by-products when 6-unsubstituted quaternary salts 149 (R3 = H) were treated with alkali under oxidative conditions (Scheme 85) (7ICC 1636). Transformation into triazoles 153 occurs in the presence of nucleofugic groups at C-3 (R1 = OCH3, SCH3) in salts 149 (Scheme 85). 

Tricyclic furo[2,3-e]pyrido[l,2-fr][l,2,4]triazinium salt 612 underwent ring transformation by reaction with carbon nucleophiles. Thus, the sodium salt of 1 generated from reaction of 1 and sodium hydride in acetonitrile, was treated with 612 to give 7-benzoyl-8,9,10,ll-tetrahydro-9,9-dimethylindenoll,2-eJpyrido[l,2-frJl,2,4-triazin-ll-one (94CB1799), which because of the enhanced delocalization of the n electronic system, it existed in two equilibrium forms 613 and 614 (Scheme 132). 

Reaction of monocyclic 1,2,3-triazines 1 with mesitylenesulfonyl-O-hydroxylamine led to the isolation of 2-amino-l, 2,3-triazinium salts 5 which could be deprotonated by base to the 1,2,3-tri-azin-2-imines 6.246,247 The imino compounds could be acylated yielding either (acylimino)-1,2,3-triazines 6a or the dimers 7. 

The formation of 1,2,4-triazinium salts by protonation or alkylation is a well-known reaction and a number of theoretical calculations on this problem have been published.15 Calculation of the protonation energies for the parent 1,2,4-triazine by an ab initio method gave the following values Nl + — H 218.7,248 218.6249 kcal mol-1 N2+-H 229.8, 222.8 kcal mol-1 N4+ — H 212.2, 211.9 kcal mol-1. 

Alkylation of l,2,4-triazin-3-amines with dimethyl sulfate was reported to yield the 1-methyl-1,2,4-triazinium salts 6 (R5 = Me).258 It was thought that alkylation of l,2,4-triazin-3-amines with iodomethane gave a 1 1 mixture of the 3-amino-l-methyl and the 3-amino-4-methyl-l,2,4-triazinium salts. However, reexamination of this reaction showed that Nl and N2 alkylated products 6 and 7 were isolated, but no 4-alkyl-l,2,4-triazinium salt.258 The formation of 2-substituted l,2,4-triazin-3-imines 8 during the alkylation of l,2,4-triazin-3-amines (R3 = H) has also been reported.257,26t> 264 When NR3R4 = NH2, the main products with methyl iodide are 2-methyl-l,2,4-triazin-3-imines 8 and the 1-methyl-1,2,4-triazinium salts 6 the minor products NR3R4 = NHMe affords predominantly the l-methyl-l,2,4-triazinium salts 6, and NR3R4 = NMe2 yields only the 1-methyl-l,2,4-triazinium salts 6.257... 

Alkylation of 1,2,4-triazine 1-oxides with triethyloxonium salts affords 4-alkyl-l-oxido-l,2,4-triazinium salts 9261 while alkylation of the 2-oxide with triethyloxonium salts yields the O-alkylated product 10.261 Reaction of 1,2,4-triazine 4-oxides with triethyloxonium salts produces 1-alkylated 1,2,4-triazinium salts 11.261... 

Alkoxycarbonyl-l,2,3-triazinium salts, which were postulated to be formed in situ in low concentration from triazines and chloroformates, have been trapped by carrying out reactions in the presence of a ketene silyl acetal or a silyl enol ether, which gives 2-alkoxycarbonyl-5-substituted... 

The reaction of triazinium salts (78) with superoxide gave 5,5 -bi(2-methyl-2,5-dihydrotriazinyls)... 

Reaction of 6-methyl-3-trimethylsilyloxy-1,2,4-triazine 1-oxide (100) with alkylating agents gives, after aqueous work-up, 4-alkyl-6-methyl-l,2,4-triazin-3-one 1-oxides (101) (Equation (5)) <86JHC1613>. Alkylation of the 1,2,4-triazine 1-oxides (102a-c) with triethyloxonium salts yielded 4-alkyl-l-oxy-l,2,4-triazinium salts (103a-c) (Equation (6)) <95UP6il-oi>. 

The formation of pyridine IV-imines by an add-catalyzed rearrangement of some diazepinones and related compounds has been extensively investigated by Moore and co-workers (Eq. 9).115 The formation of pyridine N-imines from l/f-l,2-diazepines is also known (Eq. 10).68 69,116,117 Diels-Alder reactions of pyrazoles with dimethyl acetylenedicarboxylate, in the presence of BF3, have been reported to give IV-aminopyridinium salts (Eq. II).118 l,4-Dihydropyrido[l,2-a]-as-triazinium salts and their pyrimido derivatives undergo ring contraction in boiling aqueous acid, yielding 1-aminoimidazo[l,2-a]pyridinium and pyrimidinium salts, respectively (Eq. 

Diaminopyridinium iodide undergoes reaction with ethyl aceto-acetate and acetylacetone to form somewhat unexpected products, the pyrido[l,2-a]pyrimidine derivatives 33 and 34, respectively.154 The initial step has been shown to be decomposition of 1,2-diaminopyridinium iodide to 2-aminopyridinium iodide which undergoes condensation with [i-dicarbonyl compounds. The reaction of 1,2-diaminopyridinium salt with 1,2-dicarbonyl compounds gives pyrido[ 1,2-A] [1,2,4]-triazinium salts 35.161... 

A theoretical study has been performed in order to estimate the ability of 1,2,4-triazines to undergo N-protonation reactions. The ab initio calculations, obtained using HF/6-31G, have shown that the N2-H triazinium cation is the most stable thermodynamically similar characteristics have been obtained for Nj- and N2-H 1,2,4-triazinium salts derived from protonation of 6-phenyl-l,2,4-triazine <2003CHE616>. 

It is well recognized that N-alkylation of aza-aromatic compounds is usually an irreversible process <1978AHC(22)71>. However, a feature of l-alkyl-l,2,4-triazinium salts 5 is an unusual dequaternization reaction which has been found to occur under very mild conditions on treatment of 5 with triethylamine in methanol, ethanol, or acetone solutions (Scheme 7) <1995MC104>. 

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