Guanidines 1,3,5-triazines

The discovery of fungicidal activity in guanidine, triazine, and an-thraquinone derivatives is opening new areas of fungicide research, and a few pesticides of these types are being developed commercially. 

The reaction of 4-methoxy-3-nitropyridines 129 with guanidine under similar conditions results in 3-aminopyrido[3,4-e]-l,2,4-triazine 1-oxides 130 (76MI). 

Reaction of 2,3-dichlorobenzoyl chloride with cyanide ion leads to the corresponding benzoyl cyanide (141). Condensation of that reactive intermediate with aminoguanidine 142 leads to the hydrazone-like product 143. Treatment with base results in addition of one of the guanidine amino groups to the nitrile function and formation of the 1,2,4-triazine ring. The product, lamo-trigine (144), is described as an anticonvulsant agent [31]. 

When the reaction of diethyl oxomalonate 381 was carried out with the free 5-methyl isothiosemicarbazide, triazine 281 was obtained in addition to its isomeric triazine 382. Reaction of 382 with phosphorus oxychloride gave 383, whose reaction with guanidine or benzamidine gave 384, which cyclized to 385. This represents (85JOC2293) the first example of a preparation of this bicyclic system from a 1,2,4-triazine. 

Interaction of iV-pentafluorophenylcarbonimidoyl dichloride with benzonitrile and aluminium trichloride leads to l-pentafluorophenyl-4,6-diphenyl-13 -triazin-2-one along with urea derivatives . Reaction of perfluoro-5-azanon-4-ene with a range of bidentate nitrogen nucleophiles (urea, substituted amidine hydrochlorides and guanidine), in the presence of triethylamine or potassium hydroxide, effectively provides fluorinated 1,3,5-triazines 16-19 <00JFC(103)105>. 

The main starting compound is the labeled nitroguanidine 257 obtained from guanidine with isotope-labeled potassium nitrate. Reduction of 257 to hydrazine carboximidamide 258 was carried out with zinc and, then, ring closure to 3-amino[l,2,4]triazole 259 was carried out using formic acid. Finally, the ring closure to form the [l,2,4]triazine ring - similar to other procedures presented in Scheme 54 - was perfected by reaction with nitrous acid followed by treatment with ethyl nitroacetate to 260. 

Straightforward synthesis of some substituted naphtho[l, 4]triazines 108 and quinolino[l,2,4]triazines 109-112, via the cyclocondenstion of nitronaphthalenes and nitroquinolines with guanidine have been reported <99JOC3361>. 

Azirine derivatives 318 were shown in the same article to be precursors of triazines 324 (30-35% yield) and pyrimidines 326 (30% yield) upon treatment in DMSO with guanidine and formamidine, respectively (Scheme 71). A similar pathway to that outlined above is also invoked to explain these results thus, intermediate 323 would yield 324 by electro-cyclic ring closure, whereas 326 would be formed by heterocyclization of 325 and loss of ammonia (91JOC7). 

Diamino-s-triazine-2-ol see Ammeline 1 A273 (4,6-Diamino-s-triazine-2-yl)-guanidine... 

Changing the nature of the triazine substitution pattern to the l,3,5-triazine-2,4-dione system leads to another series of herbicides, of which the best example is hexazinone (1) (75USP3902887). It is built up from cyanamide which is converted in several steps to the guanidine (2). Reaction with cyclohexyl isocyanate then gives an intermediate which can be cyclized to hexazinone (Scheme 2). 

In several related transformations, guanidines and hydrazones were employed as nucleophiles instead of carbanions that then leads to annulation of the 1,2,4-triazine ring. For example, 2-nitronaphthalene with guanidine, in the presence of an excess... 

The pyrido-l,2,4-triazines (83) and (85) were prepared in one step from the corresponding nitropyridines (345a,b) by treatment with NaOMe and guanidine, followed by base-catalyzed cyclization <76MI 717-03). 

Cyclizations of acylamidines 720 with amidines 721 or guanidines in aprotic solvents give -triazines 722 bearing three different substituents (Scheme 309) <1995JOC8428>. 

A series of condensed 1,2,4-triazines have been obtained from nitroarenes and guanidines or other TV-nucleophiles as exemplified in Schemes 241243 <1999JOC3361, 2002J(P1)696, 2006RCB1243, CHEC-III(9.02.7.1)158>. The key step in these reactions involves nucleophilic displacement of hydrogen ortho to a nitro group by the action of the iV-nucleophile followed by intramolecular cyclization to the 1,2,4-triazine system. 

The synthesis and biological activity of 2,4,6-triamino-substituted-1,3,5-tiiazines have been described <03JIC138>. The synthesis of //-substituted 2,4-diamino-6-(benzothiazolyl-2-thiomethyl)-l,3,5-triazines 11 has been achieved from guanidine derivative 9 through intermediate 10 <03KGS730>. 

Triazin 6-Amino-4-(4-niethoxy-phenyl-2-methyl- E9c, 719 (Ar-CO-NH-CS-CH3 + Guanidin)... 

Heterocycles. The reagent condenses with guanidine to give 2,4-diamino-j-triazine." ... 

A wide variety of compounds have been shown to inhibit xanthine oxidase guanidines and some triazines (F7), purine derivatives such as purine 6-aldehyde (G5), 6-mercaptopurine (S20), 2,6-diaminopurine (W8), flavonoids (B13), and Antabuse (R6). Although these compounds and the inhibitions they produce are of interest in understanding the nature of the action of xanthine oxidase, none has been useful clinically in limiting urate production. Antabuse, as a result of its action, produces other effects that (fortunately ) have not been found with allopurinol. 

A -Pyrimidinyl-iV-aryl guanidines have been cyclized with keto esters to give 1,3,5-triazine derivatives <05JGU303>. Trimolecular condensation of paraformaldehyde, primary amines and suitable isoxazolyl-iV-arylthioureas 31 using montmorillonite K-10 in diy media, under microwave irradiation afforded the corresponding isoxazolyl triazinethiones 32 <05JHC711>. 

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