Triazines reaction with cyanamide

It was found that 1,2,4-triazine 4-oxides 55 are active enough to react with cyanamide under basic conditions according to the deoxygenative mechanism to form 5-cyanamino-l,2,4-triazines 73 (00TZV1128). This reaction seems to be facilitated by the easy aromatization of cr -adducts by the Elcb elimination of water. 

On reaction of tetrazines (484) with cyanamides, the bicyclic intermediates (488) lead directly to 3-amino-1,2,4-triazines (487 R1 =NR2) by elimination of nitrogen (79CZ230). 

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). 

Melamine, a white powder, was discovered and identified by Liebig in 1834 but commercial manufacture came only in 1939, by Cyanamid Company of America with dicyandiamide as raw material. Melamine is 2,4,6-triamino-l,3,5-triazine with a structure as shown in Figure 53. On reaction with formaldehyde in aqueous solution the melamine powder dissolves rapidly on heating to form various methylol melamines, as in Figure 54. After further heating and the elimination of water the methylol melamines condense to form resinous polymers. 

The reaction of 1,2,4,5-tetrazines with cyanamides affords 1,2,4-triazines 7 directly via the bicyclic intermediate 6 and loss of nitrogen.196-i97,455,456... 

The reaction of alkyl. /V-cyanoimidates 16 with cyanamide and sodium methoxide in methanol gives 4-methoxy-l,3,5-triazin-2-amines 17 in 33 to 54% yield.403... 

On treatment with diluted hydrochloric acid or sulfuric acid at 40 "C, compound 1 forms amidinobiuret 4 (73%) with loss of nitrogen. When anhydrous hydrochloric acid is added to a solution of the potassium salt of 1 in anhydrous acetone and the resulting precipitate is treated with water, 6-chloro-l,3,5-triazine-2,4-diamine (5) can be obtained. Treatment of 1 with aqueous potassium hydroxide for 24 hours leads to the isolation of 2,4-diamino-l,3,5-triazin-6(l/7)-one 6 (45%). Reaction of 1 with cyanamide in aqueous potassium carbonate solution affords 2, which gives l,3,5-triazine-2,4,6-triamine (7, melamine, 88%) together with ammonia, carbon dioxide and nitrogen when heated in diluted mineral acid. Product 7 can be obtained similarly from tetrazine derivative 3.3 See also Section B.2.3 on 1,3,5-triazines. 

Cycloaddition of the tetrazine (317) to cyanamides R2NCN, followed by extrusion of nitrogen, gives the 1,2,4-triazines (318) in good yield. A similar reaction with iV-(thionitroso)dimethylamine (McaN—N=S) gives the triazole (319), possibly by extrusion of sulphur from an initially formed thiatriazine. " ... 

The reaction of 1,2,4-triazine 4-oxides 26 with cyanamide under basic conditions results in 4,5-dihydro-5-cyan-amino-l,2,4-triazines 135 followed by autoaromatization with the loss of water to yield 136 (Scheme 71 see also pathway b in Scheme 44) <2000RCB1122>. 

The reaction of bis(mercaptothioformylhydrazido)phthalate 4 with cyanamide yielded the bis-l,2,4-triazin-6-yl derivative 5 <01PS65>. 

Subsequently, it was shown that the reaction was catalyzed by base (48M(79)106). Dicyandiamide reacts with nitriles (the most valuable method), amidines, cyanamides, ammonia, cyanates, thiocyanates, carboxylic acids and anhydrides to yield 1,3,5-triazines (Table 13). This synthetic route has been reviewed thoroughly several times (59HC(13)1, p. 219,61MI22000, p. 650, 73ZC408). The base-catalyzed reaction of dicyandiamide with alkyl or aryl nitriles (Scheme 65) proceeds via the imino ether anion and the rate determining step is solvent dependent. In DMSO the formation of the imino ether is rate determining, but in 2-methoxyethanol the reaction between the anion and dicyandiamide controls the rate (66T157). 

Cyclotrimerization of nitriles with heteroatomic substituents are also facile and important reactions. Melamine is formed on heating cyanamide above its melting point (equation 74) (59HC(l3)l, p. 309). Substituted cyanamides react to give either the expected 1,3,5-triazine or the isomer (142). The 1,3,5-triazine is the preferred product at high temperatures, under acid catalysis, and for cyanamides with bulky substituents, whilst the isomer is favoured by basic conditions and low temperatures (Scheme 80). The mechanism of formation of (142) has been proposed (Scheme 81) (78RCR975). 

The Beirut reaction has also been employed to prepare 1-hydroxybenz-imidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [46,47], and benzo[e][l,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyanamide [48-50]. 

Similar to urea (see Section 13.2), melamine can react with formaldehyde forming a thermosetting resin. Melamine is a trimer of cyanamide and contains three amino groups that offer six possible points of reaction. Since melamine can be considered a triamine of 1,3,5-triazine, this group of resins can be included in the class of polymers with heterocycles in their structure. The first stage of the reaction of melamine with formaldehyde can be written as follows ... 

The transformation of one 1,2,4-triazine ring into another 1,2,4-triazine has been reported. Reaction of /V-substituted cyanamides with 1,2,4-triazines affords, via exclusive addition of the nitrile group across C5—N2 of the 1,2,4-triazine nucleus, the nonisolable bicyclic intermediate 16, from which trifluoroacetonitrile is eliminated to yield 1,3,5-triazines 17 as the main products. Elimination of methyl thiocyanate is a side reaction affording 1,2,4-triazines 18.2U2... 

A series of papers from Seitz s group, which also deals with examples in the 1,2,4-triazine field, describes routes to bicyclic pyridazines and pyridines. Instead of the terminal alkyne group the cyanamide unit can be used, leading to bicyclic 1,2,4-triazines. Scheme 54 offers the general reaction sequence (306) -> (307) and a selection of typical systems (308)-(310), which can be synthesized by... 

Triflic anhydride was found to be efficient for the cyclotrimerization of dialkylcyanamides 166 under mild conditions. The same reaction can be applied to aryl nitriles and thiocyanates. The reaction involves the formation of the bistrifluoroisourea intermediates 167, which react quickly with two molecules of cyanamide to afford the triazines 168 (Scheme 25) <2004S503>. 

Seitz et al. prepared various l,2,4-triazine-C -nucleosides 340 via cycloaddition of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 147 to monosaccharide-derived imido esters 339 as intermediates in their quest for new pyridine C-nucleosides <1999ZNB549, 1997ZNB851, 1995AP175>. Similarly, the same group reported the preparation of novel 2-(2 -pyrrolidinyl)pyridines from (3 )- and (R)-proline via cycloaddition of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 147 to heterodienophilic imidates or hydrazones derived from (3)- and (R)-proline <1999TA573>. Reaction of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate 150 with either 0-methylisourea or cyanamide gave... 

Reactions of 2,6-di(trihalomethyl)-substituted 1,4,3,5-oxathiadiazine 4,4-dioxides 62 with substituted cyanamides in aromatic solvents (benzene, toluene, chlorobenzene, benzonitrile) furnish stable complexes 27 including 1,4,3,5-oxathiadiazine 4,4-dioxide, symmetric triazine, and solvent (or no solvent) in a ratio of 2 2 1. The molecules involved in the complexes are joined by intramolecular (van der Waals) forces into a unified, energetically favorable supra-molecular system (Scheme 15) <2005RJ0289>. 

The byproducts biuret and cyanuric acid are observed in the largest quantity at low and moderate temperatures up to about 300 °C [36] however, additional byproducts form in smaller amounts as shown in Fig. 16.2 [11, 36, 37]. Substitution of the OH groups of cyanuric acid by NH3 yields the more stable triazines ammelide, ammeline, and melamine [36]. Ammelide may also be formed by the reaction of biuret with HNCO, if water is eliminated instead of NH3 [11]. Melamine may also be produced by trimerization of cyanamide [36] since cyanamide is an intermediate in melamine synthesis [35]. Cyanamide was not observed in a... 

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