1.2.4- Triazine 1,4-dioxides

The reaction of 1,2,4-triazine 4-oxides 8 bearing substituents at the 3, 5, and 6 positions with peroxyacetic acid proceeds as an N-oxidation process exclusively at the 1 position, resulting in 1,2,4-triazine 1,4-dioxides 14. Oxidation of 1,2,4-triazine 4-oxides 8 unsubstituted at the 5 position leads to 5-hydroxy-1,2,4-triazine 4-oxides 15 (76LA153). 

The generation of other heteroq cles from Bfx and Fx has been the subject of exhaustive investigation. The most important transformation of Bfx to other heterocycles has been described by Haddadin and Issidorides, and is known as the Beirut reaction . This reaction involves a condensation between adequate substituted Bfx and alkene-type substructure synthons, particularly enamine and enolate nucleophiles. The Beirut reaction has been employed to prepare quinoxaline 1,4-dioxides [41], phenazine 5,10-dioxides (see Chap. Quinoxahne 1,4-dioxide and Phenazine 5,10-dioxide. Chemistry and Biology ), 1-hydroxybenzimidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [42], and benzo[e] [ 1,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyan-amide [43-46] (Fig. 4). 

Chloro- and fluorosulfonylcarbamoyl chlorides were found to react with aminotriazole (42) to give [l,2,4]triazolo[5,l-c][l,2,4,6]thiatriazine-l,1-dioxide (43) <77JCR(S)238>. A thiazole-fused thia-triazine-dioxide (45) was prepared from the aminothiazole derivative (44) by chloro-sulfonylisocyanate. The observed regioselectivity in this reaction was interpreted by the preference for nucleophilic addition at the more electrophilic isocyanate which was followed by the cyclization at the sulfonyl chloride <87JMC2058>. 

Furalazine, Acetylfuratrizine, Panfuran-S. Heating nitrovin in butanol or dimethylformamide at 100—130°C affords furalazine, 6-[2-(5-nitro-2-furanyl)ethenyl]-l,2,4-triazine-3-amine (34). An improved synthesis originates with 5-nitro-2-furancarboxaldehyde and acetone, proceeds through 4-(5-nitro-2-furanyl)-3-buten-2-one followed by a selenium dioxide oxidation to the pymvaldehyde hydrate, and subsequent reaction with aininoguariidine (35). Furalazine, acetylfuratrizine (36), and the A[-A/-bis(hydroxymethyl) derivative, Panfuran-S, formed from the parent compound and formaldehyde (37), are systemic antibacterial agents. 

Phenylsulfonyl)indole 330 was converted to a ketone by a set of standard reactions followed by the selenium dioxide oxidation of the resulting acetyl goup to the ketoaldehyde 332 (Scheme 101). Methylthiosemicarbazide hydroiodide reacted with 332 to the triazine 333 in 83% yield. As Diels-Alder reactions with 1 -pyrrolidinocyclohexene failed, 333 was first oxidized... 

Electrochemical reduction of various 3,4-disubstituted-l,2,5-thiadiazole 1,1-dioxides (3,4-diphenyl- 10, phenanthro[9,10]- 51, and acenaphtho[l,2]- 53) gave the corresponding thiadiazoline 1,1-dioxides <1999CJC511>. Voltammetric and bulk electrolysis electroreduction of 3,4-diphenyl-l,2,5-thiadiazole 1-oxide 9 at ca. —1.5 V, in acetonitrile, gave 3,4-diphenyl-l,2,5-thiadiazole 8 (50%) and 2,4,6-triphenyl-l,3,5-triazine 54 (30%) (Equation 3) <2000TL3531>. 

Supercritical fluid extraction with methanol modified carbon dioxide has been applied to the determination of Triazine herbicides in soil [103]. 

Plant. In tolerant plants, atrazine is readily transformed to hydroxyatrazine which may degrade via dealkylation of the side chains and subsequent hydrolysis of the amino groups with some evolution of carbon dioxide (Castelfranco et al, 1961 Roth and Knuesli, 1961 Humburg et al, 1989). In corn juice, atrazine was converted to hydroxyatrazine (Montgomery and Freed, 1964). In both roots and shoots of young bean plants, atrazine underwent monodealkylation forming 2-chloro-4-amino-6-isopropylamino-s-triazine. This metabolite is less phytotoxic than atrazine (Shimabukuro, 1967). 

Pelizzetti et al. (1990) investigated the photocatalytic degradation of atrazine in solution in the presence of suspended titanium dioxide as a catalyst under simulated sunlight. Degradation was rapid but mineralization did not occur. Intermediate compounds included 6-hydroxy-A/-ethyl-/V -(l-methylethyl)-5 triazine-2,4-diamine, 2,4-diamino-6-chloro-A/-(l-methylethyl)-5-triazine, 2,4-di-amino-6-chloro-/V-ethyl-5-triazine, 2,4-diamino-6-chloro-5-triazine, 2,4-diamino-6-hydroxy-5-tri-azine, 2-amino-4,6-dihydroxy-5-triazine, 2-amino-4-hydroxy-6-chloro-5-triazine, 2,4-dihydroxy-6-chloro-s-triazine, 6-chloro-/V-acetyl-/V -(l-methylethyl)-5-triazine-2,4-diamine, and cyanuric acid as the final product. 

Photolytic. Pelizzetti et al. (1990) studied the aqueous photocatalytic degradation of prometon and other s-triazines (ppb level) using simulated sunlight (7, >340 nm) and titanium dioxide as a photocatalyst. Prometon rapidly degraded forming cyanuric acid, nitrates, the intermediate tentatively identified as 2,4-diamino-6-hydroxy-7V,A -bis(l-methylethyl)-s-triazine, and other intermediate compounds similar to those found for atrazine. Mineralization of cyanuric acid to carbon dioxide was not observed. 

Soil. Propanil degrades in soil forming 3,4-dichloroaniline (Bartha, 1968, 1971 Bartha and Pramer, 1970 Chisaka and Kearney, 1970 Duke et al., 1991) which degrades via microbial peroxidases to 3,3, 4,4 -tetrachlorazobenzene (Bartha and Pramer, 1967 Bartha, 1968 Chisaka and Kearney, 1970), 3,3, 4,4 -tetrachloroazooxybenzene (Bartha and Pramer, 1970), 4 (3,4-dichloroanilo)-3,3, 4,4 -tetrachloroazobenzene (Linke and Bartha, 1970), and l,3-bis(3,4-dichloro-phenyl)triazine (Plimmer et al., 1970), propionic acid, carbon dioxide, and unidentified products (Chisaka and Kearney, 1970). Evidence suggests that 3,3, 4,4 -tetrachloroazobenzene reacted with... 

Oxidation of triazine herbicides with chlorine and chlorine dioxide has been widely studied [105-108]. In the case of sulfur-containing triazines, oxidation occurs mainly via cleavage of the weakened R-S-CH3 bond rather than by addition of chlorine. Reactions of S-triazines with chlorine are faster than with chlorine dioxide, and form sulfoxide, sulfone, and a sulfone hydrolysis product. Chlorination with chlorine dioxide only produced sulfoxide [108]. Lopez et al. identified the formation of sulfonate esters during the chlorination of ametryn and terbutryn [106, 107]. Triazine DBFs identified by Brix et al. exhibited higher toxicities than the parent compounds [105]. Similar to triazines, clethodim, a cyclohexanedione herbicide, is oxidized by hypochlorite and chloramines to clethodim sulfoxide and then to sulfone [109]. 

The cycloaddition of 1 with 1,2,4-triazines (324), bearing one or more electron-accepting substituents, directly affords the 3,8-methanoaza[10]annulene 325 after loss of N2 from the cycloadduct. Similarly, the tetrazine-dicarboxylate 326 reacts with 1 via cycloaddition/cycloelimination to 327, which has norcaradiene struc-ture. a-Pyrones (328) and 1 undergo cycloaddition/C02 extrusion to 1,6-methano[10]annulenes (329). The sequence cycloaddition/C02 extrusion has also been reported for the reaction of cyclopropa[/]phenanthrene (142) with a-pyrone (328, R = H). ° Substituted 1,6-methano[ 10]annulenes 331 are obtained by analogy via cycloaddition/S02 extmsion of 1 with thiophene-1,1-dioxides (330). ... 

Three classes of compound dominate this section, namely the 6-azapteridines or pyrimido[4,5- ][l,2,4]triazines, the 7-azapteridines or pyrimido[5,4-i ][l,2,4]triazines, and the pyrazinothiadiazines, particularly the pyrazino[2,3-r ][l,2,6]thiadiazine 2,2-dioxides. None of the other systems that have appeared in this chapter show important applications. 

Only pyrazine and its benzo derivatives are easily converted into di-A-oxides, although di-A-oxides have been reported, for example, in the pyridazine, pyrimidine and cinnoline series. Oxidation of 3-amino-1,2,4-triazine 2-oxide with H202 in polyphosphoric acid at 24°C affords 3-amino-1,2,4-triazine 2,4-dioxide (78). However, 3-amino-1,2,4-triazine with peracetic or... 

Oxidation of 1-aminobenzimidazoles with manganese dioxide or lead tetraacetate can give either 1,1 -azobenzimidazoles (735) or 3-substituted benzo-l,2,4-triazines (736). Electrochemical measurements have shown that the first step in this reaction is removal of an electron from a ir-orbital of benzimidazole rather than from the A-amino group. Because the cation radical which is formed must be stabilized by loss of a proton, for (736) to form the 2-substituent must contain an NH or OH group. This is unnecessary for the formation of the azo product (735) which may form via a nitrene intermediate. 

Mesityl-2//-benzo[c]-l,2-thiazetidine 1,1-dioxide is prepared from the corresponding benzothia-triazine by photochemically induced elimination of N2 (Scheme 26) (72LA(763)46). 

Disubstituted 1,2,4-triazine 4-oxides (124) with peracids give the corresponding 1,4-dioxides (250). If the 5-position is unsubstituted the 5-oxo 4-oxides (251) are formed, and these are also the products of oxidation by potassium permanganate (76LA153). 

Oxidation of methyl ketone guanylhydrazones (686) with selenium dioxide affords the corresponding monosubstituted glyoxal derivatives (687) which cyclize to the 5-unsubstituted 3-amino-1,2,4-triazines (473) (78HC(33)189, p.360). We have already noted the cyclization of bis(alkylidene)- or bis(arylidene)-acetone guanylhydrazones (475) in the synthesis of 6-(vinyl-substituted) 3-amino-1,2,4-triazines (477) (Section 2.19.4.1.1). 

Diaminoimidazoles (741) and 1,2-diaminobenzimidazoles (743) can be oxidized by manganese dioxide or lead tetraacetate to give a useful synthesis of 3-amino-l,2,4-triazines (742) and -benzotriazines (744) (76SC457, 76TL903, 77JOC542, 78JOC2693). 

Diaryl-l,2,3,5-oxathiadiazine 2,2-dioxides (187) are valuable starting reagents which are readily prepared by treatment of the aryl cyanide with sulfur trioxide. Amidines, imidates and trichloroacetonitrile react with (187) to give a wide range of 4,6-diaryl-l,3 5-triazines in 50-90% yields under acidic conditions (equation 108) (63CB2070). 

When hydrogen chloride was introduced into a solution of the potassium salt of (27) in dry acetone, and the resulting precipitate treated with water, 2,4-diamino-6-chloro-l,3,5-triazine (32) was isolated. Compound (28) decomposed to melamine (33), ammonia, nitrogen and carbon dioxide when heated in dilute mineral acid, and the same compounds were obtained from (29) in the same way (Scheme 4). 

JOC2372). The interaction of 1,8-dehydronaphthalene 240, generated from N-aminonaphtho[[Pg.53]

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