Direct introduction of heterocyclic residues into 1,2,4‐triazin‐5(2H)ones

Abstract

3‐Aryl‐1,2,4‐triazin‐5(2H)‐ones 1a‐c react with indoles 2a‐c in trifluoroacetic acid/chloroform or in boiling butanol or acetic acid to give 3‐aryl‐6‐(indolyl‐3)‐1,6‐dihydro‐1,2,4‐triazin‐5(2H)‐ones 3a‐g. Oxidation of the dihydro‐1,2,4‐triazin‐5(2H)‐ones 3a‐e afforded 6‐(indolyl‐3)‐1,2,4‐triazin‐5(2H)‐ones 4a‐e, products of nucleophilic substitution of hydrogen in 1a‐c. Refluxing 1b with N‐methylpyrrote 5b in butanol for an extended time resulted in the formation of 3‐(4‐chlorophenyl)‐6‐(1‐meuiylpyrrolyl‐2)‐1,2,4‐triazin‐5(2H)‐one 4h. The reaction of 1a‐c with indoles 2a‐c, pyrroles 5a,b, 1,3‐dimethyl‐2‐phenylpyrazol‐4‐one (8) and aminothiazoles 9a,b in acetic anhydride affords the 1‐acetyl‐3‐aryl‐6‐hetaryl‐1,6‐dihydro‐1,2,4‐triazin‐5(2H)‐ones 6a‐s. Reaction of 1a‐c with N‐methyl‐pyrrole 5b in acetic anhydride gives beside the 1:1 addition products 6h‐k also the 2:1 addition products 7a‐c.

Asymmetric induction in the reactions of azinones with C-nucleophiles

“…2, 8 An asymmetric carbon atom, directly or indirectly incorporated into the substrate molecule (for nyl 6 pyrrolyl 1,6 dihydro 1,2,4 triazin 5(4H) ones. 10 In the present work, it was found that reflux of 6 phenyl 1,2,4 triazin 5(2H) one (2) with indoles in acetic anhy dride smoothly leads to 2,4 diacetyl 3 indolyl 6 phenyl 1,2,4 triazin 5(2H) ones 6-8 (Scheme 2, Table 1). It is noticeable that both nitrogen atoms placed in α positions to the reaction center undergo acylation.…”

C-H-Functionalization of 1,2,4-triazines: oxidation and elimination pathways of aromatization of σH-adducts

“…[16][17][18] The problem of nucleophilic substitution of hydrogen in 1,2,4 triazines was considered in a number of papers and monographs. [19][20][21][22][23][24][25] For example, a number of C nu cleophiles were reported to be successfully introduced in the 1,2,4 triazine ring, 22,23 in particular, alkylphenols 24 and crown ethers. 25 Thus, the dissolution of 1,2,4 triazines in trifluoroacetic or acetic acid results to the formation of protic NH triazinium salts, which at room temperature easily react with 2,6 dimethylphenol and resorcinol.…”

Regioselectivity in the reactions of pyrroles with 3-aryl-1,2,4-triazin-5-ones

“…[5][6][7][8][9] The reactions of 3-aryl-1,2,4-triazin-5(4H)-ones with indoles, phenols, thiazoles and pyrazolones in the presence of acetic anhydride occur via the nucleophilic addition of these heterocycles at the 6-position of the triazine ring. [10][11] The reactions of pyrrole and 1-methylpyrrole with 1a,b afforded 1-acetyl-3aryl-6-(pyrrol-2-yl)-1,6-dihydro-1,2,4-triazin-5(4H)-ones 4a,b, 5a,b, respectively, in 60-80% yields. 10 We found that the reactions of 3-aryl-1,2,4-triazin-5(4H)-ones 1 with 1-methylpyrrole in the presence of strong carboxylic acids or their anhydrides gives β-heteroarylpyrroles 2-3 with high regioselectivity.…”

“…[10][11] The reactions of pyrrole and 1-methylpyrrole with 1a,b afforded 1-acetyl-3aryl-6-(pyrrol-2-yl)-1,6-dihydro-1,2,4-triazin-5(4H)-ones 4a,b, 5a,b, respectively, in 60-80% yields. 10 We found that the reactions of 3-aryl-1,2,4-triazin-5(4H)-ones 1 with 1-methylpyrrole in the presence of strong carboxylic acids or their anhydrides gives β-heteroarylpyrroles 2-3 with high regioselectivity.…”

“…(H-3' and H-4' proton resonances), and the multiplet at 6.5-6.6 ppm belongs to the H-5' proton. 10 The structure of 3a was determined by 1 H-13 C NMR (COLOC) correlation spectroscopy. In particular, the interaction of the N-1' methyl group protons with two α-atoms (H-2' and H-5') of the pyrrole ring provides evidence for the β-addition of pyrrole to triazinone 1a.…”