1.2.4- Triazine. 3-amino-. reaction with

Aryl cyanates react with ammonia to form the bis(iminoethers) (100). These compounds form 1,3,5-triazines by reaction with a further equivalent of the cyanate (Scheme 58) (67AG(E)206). IV-Amidoamidines condense with ethyl oxalate to form 2-amino-1,3,5-triazines (equation 53) (71CPB1789). 

An amino group can also be acylated <84JHC697, 86JHC935) it reacts with sulfonyl chlorides and aryl isocyanates <86JHC935>, and also with nitrous acid to give, via the diazonium salt (281), either the triazinone by reaction with water or the chloro-triazine by reaction with chloride ions (Scheme 50). Nitrosation of 3-amino-1,2,4-triazine 2-oxides (282) and subsequent thermolysis of the diazonium tetrafluoroborate salts (283) afforded 3-fluoro-1,2,4-triazine 2-oxides (284) (Scheme 51). In one instance the diazonium tetrafluoroborate was isolated <85H(23)1969>. 

The chemistry of (difluoramino)dinitroacetonitrile was further explored as well [84,85] it underwent common transformations such as hydrolysis to (difluoramino)dinitroacetamide reaction with HCl in anhydrous methanol to form the 0-methyl imidate hydrochloride trimerization to 2,4,6-tris[(difluor-amino)dinitromethyl]-l,3,5-triazine and reaction with azides (NaNs, HN3) to make 5-[(difluoramino)dinitromethyl]tetrazoles. 

Another versatile approach, which nicely complements these Mannich-based procedures, incorporates a preformed symmetrical hexahydro-l,3,5-triazine (HHT) intermediate. In this case the phosphorus reagent reacts with HHT as a trimeric form of the normal aldimine species generated in situ between the amine or amino acid and formaldehyde. These HHT reagents can often be puritied and isolated prior to the reaction with phosphites. They are reasonably stable under neutral or slightly basic conditions, but they can readily revert back to the original amine and formaldehyde after heating with aqueous acid (25). Several can be purchased commercially. 

The [(thioacyl)hydrazino]triazines 554 were synthesized from 6-amino-5-hydrazino[l,2,4]triazines 552 by reaction with 553. Cyclization of 554 with an aqueous mineral acid gave (88S778) the triazinothiadiazine 555. 

Highly substituted pyrrolo[l,2- ][l,2,4]triazines were synthesized from pyrrole derivatives, by closure of the triazine ring. Thus, hydrolytic cleavage of some 1,2-diaminopyrroles having a 1-NH-BOC-protected amino function 43 followed by reaction with 1,2-dicarbonyl compounds afforded a one-pot access to the corresponding bicyclic heterocycles 44 (BOC = f-butoxycarbonyl Equation 6) < 1997J(P 1)1829>. 

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. 

In Scheme 38, two novel cyclizations are shown where the five-membered ring is formed during the reactions. Thus, some 2-amino[l,3,5]triazines 242 were subjected to ring closure by reaction with various halomethylcarbonyl compounds... 

The pyrimido[4,5- ][l,2,4]triazines (6-azapteridines) 18a and 18b, shown in Scheme 18, were formed upon the reaction of the ethyl l,2,4-triazine-6-carboxylates 121 with benzamidine, a reaction which proceeds via the action of boiling acetic acid upon the characterized intermediate salt 122 <2003CCC965>. The same researchers (Scheme 19) also showed that the 5-amino-l,2,4-triazine-6-carboxamide 123 (R =OMe) can undergo reaction in neat benzaldehyde to furnish a low yield of the 6-azapteridine 18b. More importantly, the 5-amino-l,2,4-triazine-6-carboxamides 123 were found to undergo reaction with triethyl orthoformate to yield the 6-unsubstituted-3-arylpyr-imido[4,5-( ][l,2,4]triazines 18c and 18d, also shown in Scheme 19 (R = H) <2003CCC965>, one of only a few entries to such compounds. 

The pyrimido[4,5- ]-l,2,4-triazines 19 were synthesized from the 5-amino-l,2,4-triazine-6-carboxylate 128 upon reaction with an aryl isocyanate in the presence of pyridine, with the appropriate aryl isocyanate acting as a source of two of the ring atoms, as shown in Equation (18) <2003ARK98>. 

The pyrazolo-fused pyrimido[4,5-< ]-l,2,4-triazine 35 was synthesized using the 5-amino-6-cyano triazine 131 (Scheme 21) as the precursor. Reaction with phosgeniminium chloride gave the amide halide intermediate 132 which in turn produced the pyrimido[4,5-< ]-l,2,4-triazine 35 upon treatment with gaseous hydrogen chloride <1996T3037>. 

In common with most other sections in this chapter, progress in areas other than the azapteridines is limited to only a few publications. Thus, as shown in Equation (25), the amino-(thioxo)-triazine 161 acts as the 3-heteroatom component and undergoes a regiospecific cyclocondensation reaction with the dichlorocinnoline 160 to give the condensed pyridazino[3,4-( ]-l,3,4-thiadiazine tetracycle 162 via loss of two units of HCl <2000PS315>. 

A number of 1,2,4-triazines such as the parent compound, the 3-methylthio, 3-methoxy and 3-amino-6-bromo derivatives add ammonia in liquid ammonia at -44 °C to the N(4) —C(5) bond to give adducts of type (lOl), as was shown by XH and 13CNMR spectroscopy. No reaction was observed with 3-methoxy-l,2,4-triazine 1-oxide (71), other 3-amino-l,2,4-triazines, or compounds with a substituent in the 5-position. As was shown using lsN-enriched ammonia, an equilibrium between the covalent addition products (101) and the open-chain isomers (102) does not occur (78RTC273). 

Triazine and some of its 3-methoxy, 3-methylthio or 3-amino derivatives (103) with the 5-position unsubstituted react with potassium cyanide to afford two products, the i-triazinyls (105) and the l,2,4-triazine-5-carboxamides (104). These are proposed to be formed via a cyanide adduct (73JHC343, 74JHC43). The bi-l,2,4-triazinyls (105) were also isolated when the triazines (103) were treated with sodium methoxide or potassium in liquid ammonia. It is suggested that the methoxide-catalyzed dimerization proceeds via an anionic intermediate (106), while the reaction with potassium in liquid ammonia occurs via a free radical process. 

Amino groups react very easily with aldehydes or ketones, and with aldehydes in the presence of amines, they can be acylated by the usual acylating agents, and they react with amidacetals, Vilsmeier reagents and nitroso compounds (Scheme 12). As mentioned earlier, alkylation leads mainly to AT(2)-alkylated products. The hydrazino group reacts in the same way as the amino group with aldehydes or ketones, with acyl chlorides or carboxylic anhydrides, with sulfonyl chlorides, ortho esters, carbon disulfide and with nitrous acid. The last three reactions have mainly been used for the synthesis of condensed 1,2,4-triazines. 

The cyclization of a-hydrazinohydrazones (653) with ketones has been used for the synthesis of 4-amino-2,3,4,5-tetrahydro-l,2,4-triazines (654), and their reaction with phosgene affords 4-amino-4,5-dihydro-1,2,4-triazin-3-ones (655) (78HC(33)189, pp. 608, 656). 3-Thioxo-l,2,4-triazine-5,6-dione (657) was obtained when oxamohydrazide (656) reacted with thiophosgene (76ACS(B)7l). 

The reaction of melamine with formaldehyde is a useful one, as the initial product (39) forms a resin on heating. Such condensates are very important polymers (see Section 2.20.6.3 and Chapter 1.11). Melamine and other amino-1,3,5-triazines form salts with aqueous acids. In addition, the amino-1,3,5-triazines form potassium and silver salts (58CRV131). 

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