1.2.3- Benzotriazine ring

The third known benzologue, the pyrido[l,2-c][l,2,4]benzotriazine ring system, was synthesised by two different methods. In the first synthesis or//io-piperidinophenyl diazonium sulfonate (173) was cyclized with sulfur dioxide, then treated with warm dilute sodium hydroxide to give (174) (Equation (38)) <68CC923>. The other synthesis is based on an abnormal reaction of cyclohexanone hydrazones (175). Instead of Fischer cyclization to carboline derivatives, another reaction took place in HCl affording 6-cyclohexyl derivatives (176) (Equation (39)) <70KGS186>. 

Figure B2.4.1. Proton NMR spectra of the -dimethyl groups in 3-dimethylamino-7-methyl-l,2,4-benzotriazine, as a fiinction of temperature. Because of partial double-bond character, there is restricted rotation about the bond between the dunethylammo group and the ring. As the temperature is raised, the rate of rotation around the bond increases and the NMR signals of the two methyl groups broaden and coalesce.

Photolytic nitrogen elimination from 8f/-quinazolino[3,2-c][l,2,3]benzotriazin-8-one (1) leads to two intermediates, only one of which can be isolated. When the reaction is performed in the presence of nucleophiles, both intermediates react, via ring enlargement, to provide di-benzo[l,5]diazocines.43 In addition to morpholine and methanol, other alcohols or water can be used as the nucleophile. 

There is only one reported synthesis of a bcnzannulated 1,2,4-triazocine system. 2-Phenylbenz-azete (1), which can be generated from 4-phenyl-l,2,3-benzotriazine by pyrolysis, is reacted with tetrazine 2 to give a [4 + 2] adduct, which loses nitrogen and finally results in the eight-membered-ring derivative after valence isomerization.2... 

Reaction of triazenes 112 with -BuLi and subsequent treatment with di-fer/-butyl dicarbonate afforded the tricycles 113 as single diastereomers. The analogs of 112 with two alkyl substituents on the N atom (when N atom is not incorporated in a ring) gave diastereomeric mixtures of the corresponding benzotriazines under the same conditions (Equation 12) <2002AGE484>. 

As mentioned in Section II,D,l,a, the presence of a r-butyl or phenyl group at position 5 of the 1,2,4-triazine ring does not prevent addition of the amide ion to that position. Therefore, it becomes of interest to investigate whether in the amino-dehalogenation of two annelated 3-chloro-l,2,4-triazines, i.e., 3-chloro-l,2,4-benzotriazine (123) and 3-chlorophenanthro[9,10-e]l,2,4-triazine (125), using potassium amide/liquid ammonia, the Sn(ANRORC) process would be involved. Both compounds... 

The ring-chain equilibrium 80A SOB has been observed (83CJC179 85CJC2455 86CJC250 87CJC292) in solutions of 4-hydroxy-3,4-dihydro-1,2,3-benzotriazines. The tautomerization is accompanied by the ready dehydration SOB SI, especially in the derivatives SO (R = Me = alkyl) (75CJC3714). 

Lead tetraacetate oxidation of 3-substituted 1- and 2-aminoindazoles 6 and 7, has been shown by Rees to result in rapid and almost quantitative conversion into 4-substituted 1,2,3-benzotriazines (8, R = Me, OMe, Ph). 1,2,3-Benzotriazine (8, R = H) was prepared similarly, and for the first time, by carefully controlled oxidation of either 1- or 2-aminoindazole (6, 7, R = H). These remarkable ring expansion reactions, which apparently proceed via the formation of intermediate nitrenes, appear to be a direct and logical extension of original work by Bamberger and Goldberger in 1898 on the oxidative ring expansion of... 

There are two general ring syntheses available for the preparation of 3-substituted l,2,3-benzotriazin-4(3//)-ones, namely, (i) diazotization of anthranilamide and its derivatives and (ii) cyclization of 1-alkyl- or 1-aryl-3-(o-carbalkoxy)triazenes, and both reactions have been studied in considerable detail. 3-Substituted l,2,3-benzotriazin-4(3//)-ones have also been obtained by alkylation and acylation of l,2,3-benzotriazin-4-one these last reactions are discussed separately (see Section II, C, 3). 

Hydrolysis of condensed 1,2,3-triazines results in cleavage of the heterocycUc ring and is in many respects an unexceptional and fully predictable type of reaction. The relative ease with which ring fission takes place, and the products formed, depend almost entirely on the nature of the substituents at the 3- and 4-positions and on the reaction conditions employed. Moreover, hydrolysis under basic conditions normally leads to fission of the N,—C4 bond whereas under acidic conditions most 1,2,3-benzotriazine derivatives behave as masked diazonium compounds, and hydrolysis proceeds with fission of the Nj— N3 bond and transient formation of a diazonium compound, from which the observed products are ultimately derived. Hydrolysis of certain derivatives probably also involves covalent hydration as the key step. 

Very little is known about the susceptibility of the ring nitrogen atoms in 1,2,3-triazine derivatives to N-oxidation. Attempts to oxidize the N-aryl- 77 and iV-alkyltriazinium (79) betaines to the corresponding 1-oxides under a variety of conditions were unsuccessful, and the betaines were recovered unchanged even after prolonged exposure to powerful oxidants.It has been reported that oxidation of the 4-arylthio-1,2,3-benzotriazine (109) takes place at nitrogen rather than sulfur, and the product has been formulated as the Nj-oxide (110) or the N,-isomer. The evidence in favor of structure 110— the lack of bands... 

In contrast to the above situation with respect to oxidation of the ring nitrogen atoms of 1,2,3-triazines, oxidation of derivatives of 3-amino-l,2,3-benzotriazin-4-(3/0-one (101a) has proved to be of considerable interest and has been investigated in some detail by Rees and his colleagues. Treatment of 101a with lead tetraacetate at 80° has been shown to give benzyne in very low yield, but at room... 

No detailed studies have been carried out on electrophilic substitution of the homocyclic ring(s) in condensed 1,2,3-triazine derivatives. Nitration and bromination of 3-phenyl-1,2,3-benzotriazin-4(3 -one (10, R =... 

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