Nucleophiles triazine reactions with

Nucleophilic addition using organometallics showed that the C-4 position of (la) is a hard reaction site, whereas the C-5 position has soft reactivity (Equation (15)) <85CC1370>. These results are in accord with those from MO calculations. Softer nucleophiles such as organocopper reagents underwent a redox reaction with triazine to give 2,5-dihydro derivatives without ring substitution. 

Cyanuric fluoride behaves much the same as cyanuric chloride but its higher reactivity leads to nucleophilic reactions with aromatic amines, which act as carbon nucleophiles. This is a useful advantage for cyanuric fluoride, as a synthetic reagent, for the synthesis of these triazine derivatives with carbon substituents. 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

In Scheme 7, ring-opening reactions of some fused pyrazoles are shown. Thus, Baraldi et al. <1999S453> described that the pyrazolo[l,5-<7][l,2,4]triazine-dione derivative 72 is sensitive toward nucleophiles its reaction with benzylamine at room temperature gives rise to the acyl semicarbazide 73 in high yield (78%). 

In the reactions with phosphonio-a-methoxycarbonyl-alkanides, the products of type 261 derived from 1,3-cycloaddition can rearrange to the tautomeric lif-pyrazolo-triazole (87MI2). The reaction of 3-diazopyra-zoles and 3-diazoindazole with acyl-substituted phosphonium ylides led to pyrazolo-triazine and indazolo-triazine derivatives 266 instead of the expected triazole compounds (8IJHC675). In this case, the ylides, which can exist as phosphonium enolates, possess nucleophilic and electrophilic centers in a /8-relationship, giving [7 + 2] or [11 -I- 2]cycloaddition reactions. With dimethylsulfonio-a-aroyl-methanides, very complex, temperature-dependent mixtures were obtained, in some cases with sulfur retention (87MI3). 

Nucleophilic substitution with heteroaryl halides is a particularly useful and important reaction. Due to higher reactivity of heteroaryl halides (e.g. 35, equation 24) in nucleophilic substitution these reactions are widely employed for synthesis of Al-heteroaryl hydroxylamines such as 36. Nucleophilic substitution of halogen or sulfonate functions has been performed at positions 2 and 4 of pyridine , quinoline, pyrimidine , pyridazine, pyrazine, purine and 1,3,5-triazine systems. In highly activated positions nucleophilic substitutions of other than halogen functional groups such as amino or methoxy are also common. 

Nucleophilic substitution of the 4-chloro group of the 4-pyranotriazines 103 with hydrazine gives the 4-hydrazino-triazines 104, which can be further elaborated to the corresponding azides 105 or cyclized upon reaction with formic acid or carbon disulfide to give the triazolotriazines 106 or thioxotriazolotriazines 107, respectively (Scheme 11) <2005HC0495>. 

The arylfuro-fused pyrido[l,2-/ ][l,2,4]triazinium salt 179 undergoes reaction with methyl hydrazine to give the zwitterionic pyrido-fused pyridazino[3,4- ][l,2,4]triazine 31 as shown in Scheme 32 <2003ARK62, 1997CC757>. Nucleophilic attack of the hydrazine at the bridgehead results in the elimination of an enol that then allows ring closure via attack of the other hydrazine nitrogen onto the carbonyl of the keto tautomer. 

The characteristic reaction is ring cleavage. The reaction between 1,3,5-triazine and a primary amine (Scheme 7) is typical. Further examples of reactions with nucleophiles are shown in Scheme 8 (63AG(E)309). 

There have been reviews of nucleophilic substitution103 and of deoxidative nucleophilic substitution 104 in heterocyclic A -oxidcs. Stable carbon-carbon-bonded adducts, such as (22), have been reported from the reactions of 6-phenyl-1,2,4-triazine 4-oxides with phenols oxidation of the adducts may be achieved by reaction with potassium permanganate in acetone.105... 

Asymmetric synthesis of primary amines by nucleophilic 1,2-addition of alkyl-lithiums to aldehyde SAMP/RAMP hydrazones has been reported in detail.105 On reaction with a range of lithium alkyls, 1,3,5-triazinc has been found to form 1,4-adducts which yield 1,4-dihydrotriazines on hydrolysis 106 in contrast LiNR2 or LiCR3(thf)2 promote 1,3,5-triazine ring-opening reactions. 

Base-catalyzed hydrogen exchange, 16, 1 Basicity and acidity of azoles, 41, 187 Behavior of monocyclic 1,2,4-triazines in reactions with C-, N-, O-, and S-nucleophiles, 46, 73 1-, 2-, and 3-Benzazepines, 17, 45 Benzisothiazoles, 14, 43 38, 105 Benzisoxazoles, 8, 277 29, 1 Benzoazines, reactivity with nucleophiles,... 

There are three groups of substrates for which SNH reactions are especially characteristic (i) neutral azines and azoles (ii) azinium and azolium salts and (iii) nitro-arenes. Their electron-deficiency and, thus, their ability to react with nucleophiles strongly differ from each other. Azinium salts are the more electrophilic and are able to add even neutral nucleophiles very easily. Triazines,. v-tetrazines and polynitro-arenes also possess high electrophilicity. At the same time substrates such as pyridine (82JHC1285, 72JA682) and cinnoline (03CHE87), at a low temperature (e.g. in liquid ammonia as a solvent), do not react even with sodium amide. It should also be... 

---