2- Aryl-1,2,4-triazine-3,5-diones

Aryl-1.2,4-triazine-3,5-dione are a new class of light activated membrane disrupting herbicides. They are active on both grass and broadieaf weeds at low rates. The synthesis, structure-activity relationships and mechanism of action are presented. 

In conclusion, the 2-aryl-1,2,4-triazine-3,5-diones are a new class of membrane disrupting herbicides. We have demonstrated preemergence tolerance toward soybean and postemergence tolerance toward corn. The mechanism of action has been found to involve inhibition of protoporphyrinogen oxidase which results in the build-up of a photodynamic toxicant, protoporphyrin IX. 

The reaction of 1,2-dicarbonyl compounds (477) with amidrazones (478) is the best method for the synthesis of alkyl-, aryl- or hetaryl-substituted 1,2,4-triazines (481) (78HC(33)189). Mixtures result unless the dione (477) is symmetrical. 

The reaction of 1,2-dicarbonyl compounds (452) with amidrazones (453) is the best method for the synthesis of alkyl, aryl or hetaryl substituted 1,2,4-triazines (78HC(33)189, p. 195). No limitation of this synthetic principle is reported, except that it is, of course, preferable for the dione (452) to be symmetrical. The best reaction procedure is to add the dicarbonyl compound to a solution of the free amidrazone, or amidrazonium salt in the presence of one mole of base, and allow a reaction time of about 12 h. Since the first step of this reaction, i.e. condensation of the hydrazono group with one carbonyl group, is fast, while the second, i.e. condensation of the amide group with the other carbonyl, is slow, the intermediate (454) has been isolated in a few cases. This method has been used also for the synthesis of compounds containing more than one 1,2,4-triazine nucleus, and for the parent 1,2,4-triazine (1) (68CB3952). 

A new, simple, synthesis of 2,4-diaryl-l, 3,5-triazines is shown in Scheme 1. It arose from an attempt to obtain the pyrano[4,3-rf]pyrimidine system by reacting aryl amidines with the 3-methoxymethylenedihydropyran-2,4-dione (1 X= CH2). As well as the desired products, diaryl-I,2,3-triazines were obtained in 30-40% yield. The use of 5-methoxymethylene-2,2-dimethyl-l,3-dioxan-4,6-dione (1 X= 0)(derived from Meldrum s acid) gives the triazines in better yield (> 50%). It was also observed that 3-methoxymethylenefuran-2,4-dione reacted with 5-methylisothiouronium bromide to yield 2,4-bismethylthio-l,3,5-triazine [95M99]. 

Other claims are the isothiazolo[4,5-d][l,2,3]triazine-4-ones (170) for the treatment of gout and eschemia <86EUP274654>, the 3-aryl[l,2,5]thiadiazolo[3,4-d]pyrimidine-7-ones as antiallergics <90EUP349239>, 3-dialkylaminoethyl-l,2,3-triazolo[4,5-d]pyrimidine-5,7-diones as bronchodilators <88EUP272226>, and the 5-aryl-1,2,3-triazolo[4,5-d]pyrimidines as antihypertensives <88USP4923874>. 

Cyclohepta[4,5)pyrrolo[l,2-fl]imidazoles, 2-aryl-, halogenation. 59, 283 Cyclohepta[4,5)pyrrolo[3,2-e][l,2,4]triazine, 3-chloro- 10-(4-chlorobutyD-5,6,7,8,9,10-hexahydro-, 59, 50 3//-Cyclohept(e]isoxazoles, 3a,4,5,6,7,8-hexahydro-, 60, 311-3 Cyclohex-2-en-l-ones, 2- and 3-bromo-, regioselectivity of nitrile oxide cycloaddition, 60, 304 Cyclols, piperazine-2,5-dione-related, 57, 211-7... 

Todorovic et al. [21] gave the synthesis of a library of 3-aryl-pyrimido [5,4-e] [l,2,4]-triazine-5,7-(lH,6H)-dione (v) following microwave approach. The use of microwave irradiation allowed the rapid reaction times and good yields of products. It also avoids the use of metal salts. 

Todorovic N, Giacomelli A, Hassell JA et al (2010) Microwave-assisted synthesis of 3-aryl-pyrimido[5,4-e][l,2,4]triazine-5,7- (lH,6H)-dione libraries derivatives of toxoflavin. Tetrahedron Lett 51 6037-6040... 

Ring-degenerate transformations initiated by the nucleophilic addition at C-5 of the 1,2,4-triazine ring have also been reported to occur in reactions of 4-aryl-substituted 3-methylthio-l,2,4-triazine-3,5-diones with hydrazine hydrate (Scheme 80). This ANRORC mechanism involves the open-chain compound 138 as intermediate (80JHC1733 81JHC953). 

Efficient synthetic routes for 2-, 4- and 6-aryl-l,2,4-triazine-3,5-diones have been reported. Cyclization of 2,6-difluorophenylpyruvic acid 16 with 2-aryl-5,5-... 

Alkyl- or aryl-1,2,4-triazines without a substituent in the 5-position are oxidized by peracids to 1,2,4-triazin-5-ones, or 1,2,4-triazine-5,6-diones if the 6-position is also unsubstituted. 60,235 Oxidation of 3-unsubstituted and 3-methoxy-1,2,4-triazines with peracids produces the 1-oxides 3 in both cases.236... 

Some substituent replacements in this area follow pathways incorporating a Dimroth rearrangement. Thus, 3-alkylthio-4-aryl-l,2,4-triazin-5(4//)-one derivatives (197) react with ammonium acetate in acetic acid under reflux for 4 hours to give mainly the 3-arylamino-l,2,4-triazin-5(2//)-ones (198) 4-aryl-l,2,4-triazine-3,5(2/7,4//)-diones (199) are minor products (Equation (19)) <83H(20)5i>. 

The C-C-C-N-N-N mode b of cyclization is represented by the cyclization of l-aryl-3-alkyl- (or aryl-) (3-hydro-xypropyO-triazenes giving 3,4,5,6-tetrahydro-l,2,3-triazinium salts 31 (Equation (103), Section 9.01.9) and by the preparation of l-alkyl-l,4,5,6-tetrahydro-l,2,3-triazines 30 (Equation 104). There is flexibility in the choice of substituents (alkyl, aryl). Highly functionalized 2,3,4,5-tetrahydro-l,2,3-triazin-4,5-diones (CA 2,3-dihydro-l,2,3-triazine-4,5-diones) 41 are available from the cyclization of 3-diazo-2-oxopropionic acid derivatives, but variation seems to be limited to the choice of the N-3 substituent (Equation 106). 

Bayer introduced 2-aryl-l,2,4-triazine-3,5-diones with the 2,4-dihalo-5-aminoalkylsulfonylphenyl, such as 102 [109] and 103 [110] the aromatic substitution pattern is reminiscent of sulfentrazone (15). 

Synthesis, Herbicidal Activity, and Action Mechanism of 2 Aryl-l,2,4-triazine-3,5-diones... 

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