1.3.5- Triazines amidines

Crude yield. h Determined by IR spectroscopy. Ratio (amidine/triazine) 6 1. Determined by MS. Amidine hydrochloride. 

Substances of this type have hitherto received little attention. One of the reasons appears to be the limited possibilities of preparation. The only known method of preparation, described by Woolley et ai./ proceeds from the derivatives of 4-aminoimidazole-5-carboxylic acid. The amide of this acid (142) is treated with nitrous acid to yield 4-hydroxyimidazo [4,5-d]-i -triazine (2-azahypoxanthine) (143), the amidine (144) yielding the 4-amino derivative (2-azaadenine) (145) under the same conditions. 2-Azahypoxanthine was probably obtained in the same way earlier but was not identified. ... 

A convenient synthesis of trisubstituted 1,3,5-triazines uses acylamidines 1 and amidines < 95JOC8428 >, whilst l,3,5-triazin-2(l/f)-ones 3 are obtained from N-acyl-lV -carbamoyl-S-methylisothioureas 2 <96H(43)839>. 

Der hier gegebene Reaktionsmechanismus macht gleichzeitig das bei der Anwendung freier Amidine beobachtete Auftreten 2.4-disubstituier-ter s-Triazine (LXVIII) erklarlich, indem zwei Mole des Zwischenpro-duktes LXIVa unter Austritt der Nebenprodukte Ammoniak und Formamidin miteinander reagieren. 

Synthesis of the sym-Triazine System. I. Trimerization and Cotrimerization of Amidines. J. Amer. chem. Soc. 81, 1466 (1959)-... 

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>. 

Furthermore, it was pointed out that, whereas the formation of the amino adduct is fast and the formation of the product slow, it is possible that an equilibrium exists among the starting materials, their 1 1 a-amino adducts, and their open-chain amidines (Scheme 11.54). When this is the case, one may expect that, if the amination of phenyl-1,3,5-triazine is stopped before complete conversion, the retrieved starting material should be N-labeled. This has indeed been found. This behavior is in agreement with that observed with the Chichibabin amination of 4- and 5-phenylpyrimidine. 

Triazines are formed from AAs after being transformed with DMF-DMA into amidines and subsequent treatment with hydrazine [90H(30)393]. Esters of heterocyclic dehydroamino acids reacted in a similar... 

Amidines react with derivatives of cyanic esters to give a variety of 1,3,5-triazines with an aryloxy substituent. Typical examples are RC(NH)NH2 + (521) —> (522), and (523) —> (524) (72AG(E)949). 

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). 

Nearly all such syntheses are based on the use of amidines as one of the starting reagents. The role of amidines in the synthesis of 1,3,5-triazines has been reviewed recently by Gautier et al. (B-75M122000). 

Base-catalyzed trimerizations are facile also for example, trifluoromethyl cyanide trimer-izes in the presence of ammonia, presumably through the formation of the amidine intermediate (139 Scheme 77) (67JOC231). Similarly, perfluoro-n-propyl cyanide forms the 1,3,5-triazine in the presence of sodium methoxide, probably via the imidate (140 Scheme 78) (52JA5633). 

Substituted amidines are of limited use in the synthesis of symmetric 1,3,5-triazines. Only formamidine or amidines bearing strongly electron withdrawing groups react readily. The proposed mechanism (59JA1466) resembles that of the trimerization of imidates (Scheme 87). 

The reaction between amidine salts and acetimidates or propionimidates provides a valuable route to unsymmetrical 1,3,5-triazines bearing two methyl or two ethyl groups respectively (equation 90). Yields vary, and mixtures can be formed (Table 18). The reaction does not work well for amidines with large alkyl substituents (62JOC3608). 

Table 18 Synthesis of 1,3,5-Triazines from the Reaction of Imidates and Amidines (62JOC3608)...

Bader has described the first preparative route to 1,3,5-triazines containing three different alkyl or aryl substituents (65JOC702). The initial step is the formation of an acyl imidate (162) followed by condensation with an amidine to give the product (Scheme 100). Although mixtures are formed, the method is valuable because such triazines are otherwise very difficult to prepare. Typical examples are given in Table 19. 

The isocyanates play a most important role in the syntheses of l,3,5-triazine-2,4-diones. Two equivalents of the isocyanate react with an equivalent of another reagent, usually an amidine or imine, to yield the desired products. Once again the reaction occurs via a dipolar intermediate (165 Scheme 103) (see Sections 2.20.4.5.3 and 2.20.4.6.1). 

Recently, it has been shown that some 1,2,4-triazines react with aryl amidines to form the 1,3,5-triazines (184) and (185) (equation 107) (81TL1393). It is proposed that the... 

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). 

The 2-alkyl and 2-aryl derivatives are best prepared by the reaction between 1,3,5-triazine and an imidate or amidine (see Section 2.20.3.1.2). 2-Amino-l,3,5-triazines may be prepared efficiently by (a) treatment of 1,3,5-triazine with 1-amidinopyrazole (see Section 2.20.3.1) (b) condensation of triformidomethane and a formylguanidine (see Section 2.20.4.3.3). 2-Aryloxy derivatives are produced by hydrogenation of the corresponding dichloro-l,3,5-triazine derivative (see Section 2.20.3.12). 

Triazines containing two different substituents are formed by a variety of methods. The guidelines described above are applicable to these compounds also (see Section 2.20.4.9.4). The condensation of imidates with amidines provides a valuable route to 6-substituted 2,4-dialkyl-l,3,5-triazines (see Section 2.20.4.6.2). 

Triazines with three different substituents are formed by variations on the above methods. There is no efficient route to trialkyl or triaryl derivatives, although the reaction of acylimidates and amidines has met with some success (see Section 2.20.4.6.2). In general the best routes available are as follows, (a) Substitution reactions of cyanuric chloride, (b) The condensation of Af-cyanoamidine with chloromethyliminium salts, (c) 2-Aryl-1,3,5-triazin-2-ones may be efficiently prepared by ring closure reactions on AT-(a-chloroalky-lidene)carbamoyl chloride and amidines (see Section 2.20.4.4.1). 

Thallium complexes amidines, 205 phthalocyanines, 863 porphyrins, 821 triazines, 205 Thallium(I) complexes... 

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