1.2.4- Triazines with nucleophiles

Apart from these indexes, the present volume contains four chapters spanning a wide range of heterocyclic chemistry. 1,5-Diazocines by Perlmutter, continues his coverage of important eight-membered heterocycles (cf. Azocines in Volume 31, and 1,4-Diazocines in Volume 45). Charushin, Alexeev, and Chupahkin from the Soviet Union, and Van der Plas from Holland cover reactions of 1,2,4-triazines with nucleophiles, a subject to which they bring much expertise. 

N. V Alekseeva, L. N. Yakhontov, Reactions of Pyridines, Pyrimidines, and 1,3,5-Triazines with Nucleophilic Reagents, Russ. Chem. Rev. 1990, 59, 514-530. 

Reaction of 1,2,3-triazine with nucleophiles usually leads to ring opening via attack at C-4. However, silyl enol ethers react with chloroformate/l,2,3-triazine salts to give 5-substituted 2,5-dihydro-l,2,3-triazines, which can be re-aromatised using cerium(lV) ammonium nitrate. In this case, initial addition of the electrophile takes place at N-2, leading to the specific activation of C-5. ... 

The treatment of 3-amino-1,2,4-triazine 2-oxides 1 or 3-amino-1,2,4-benzotri-azine 1-oxides 29 with nitrous acid proceeds as a diazotization reaction, but the diazo compounds have never been isolated owing to the easy displacement of the di-azo group with nucleophiles. Thus the reaction of 3-amino-1,2,4-triazine 2-oxides 1 with sodium nitrite in hydrochloric or hydrobromic acids leads to the corresponding 3-halogen-1,2,4-tiiazine 2-oxides 119 or 3-bromo-l,2,4-benzotriazine 1-oxides 120 (77JOC546, 82JOC3886). 

Tris(trinitromethyl)-l,3,5-triazine reacts with nucleophiles such as alcohols and amines to give products in which the trinitromethyl groups are displaced in turn to yield mono, di, then trisubstituted compounds. Some of the products which have been obtained are shown in Scheme 12 <95CHE(31)596>. 

Most of the known types of reactions of condensed 1,2,3-triazines with both electrophiles and nucleophiles have necessarily been included in the appropriate preceding sections. The following brief discussion is therefore restricted to coverage of a number of reactions that have not so far been mentioned and, in most cases, have not been investigated in detail. 

Vapor-phase flash pyrolysis of 4-phenyl-1,2,3-benzotriazine (8, R = Ph) at 420°-450° gives a mixture of biphenylene, 9-phenylacridine, unchanged triazine, and the 2-phenylbenzazete (158). Compound 158, which is stable at -80°, dimerizes when warmed to room temperature and reacts readily with nucleophiles and 1,3-dienes. The thermally more... 

The above reactions are relatively straightforward in terms of mechanism. There are, however, a number of important transformations based on 1,3,5-triazine as starting material, and which result in formation of either pyridine or pyrimidine derivatives. 1,3,5-Triazine reacts very readily with nucleophiles, probably as outlined in equation (197) if X in (31) is a suitable electrophile, cyclization can take place. Thus, when X = CN, 4-amino-5-cyanopyrimidine is obtained, and other illustrative examples are shown in equation (198). This procedure is particularly useful for the preparation of 2-unsubstituted pyrimidines, a class of compound which is not readily accessible by other types of ring formation. The reverse type of transformation, i.e. of pyrimidines to 1,3,5-triazines, is also an important synthetic method, and one which has been studied in detail. Two types of substituted... 

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). 

Most mono-anchor dyes are derivatives of cyanuric chloride (2,4,6-trichloro-1,3,5-triazine [108-77-0]), a molecule of wide synthetic potential because the three chlorine atoms on the triazine ring differ in their reactivities [12], The first chlorine atom exchanges with nucleophiles in water at 0 - 5 °C, the second at 35 -40 °C, and the third at 80 - 85 °C. A wide variety of triazinyl dyes can thus be prepared by careful selection of the reaction conditions. Condensation of cyanuric chloride with a chromophore ( Chrom. ) containing an amino group yields the highly reactive dichlorotriazinyl dyes 1 [11]. These very reactive dyes are sensitive to hydrolysis, and a suitable buffer is usually added to the powdered dye to increase its stability [13],... 

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,... 

The Diels-Alder reaction of 5-acetyl-3-methylthio-l,2,4-triazine with cyclic enam-ines produces 3-acetyl-l-methylthiocycloalka[c]pyridines, which are synthons for the preparation of sempervirine and its analogues.126 Cycloadditions of aryl-substituted 1,2,4-triazines (117) with 2-cyclopropylidene-l,3-dimethylimidazolidine (118) yield Diels-Alder adducts (120) that eliminate N2 to form dispiropyridines (121), which rearrange to pyrrolo[3,2-c]pyridines (122). At low temperatures, zwitterions (119) formed by nucleophilic attack of (118) on the triazines could be detected spectroscopically and, in some reactions, isolated (Scheme 34).127... 

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... 

The tricyclic furo-fused 1,2,4-triazinium salt (74 X= O) reacts with nucleophiles such as sodium hydrogen sulfide, sodium diethyl malonate, or sodium ethyl cyanoacetate to yield the new ring systems thieno[2,3-e pyrido[l,2-Z>]-l,2,4-triazinium perchlorate (74 X= S) and cyclopenta(e]pyrido[ 1,2-b -1,2,4-triazines (75) [94CB1799]. 

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