1.2.4- Benzotriazines, 1,4-dihydro- from

Dihydro-1,2,3-benzotriazines (452) result from 2-aminobenzylamines (451) with nitrous acid <78HC(33)9l). 

Dihydro-1,2,4-benzotriazines (485) are obtained from the reaction of A -(2-chlorophenyl)-imidates (484) with hydrazines. They can be oxidized to l-alkyl-l,2,4-benzotriazinium salts (486) (67MI21900). 

Dihydro-l,2,4-benzotriazines are isolated from the reduction of 1,2,4-benzotriazines 4 with sodium dithionite346a,b or sodium borohydride.373 The products obtained by reduction of l,2,4-benzotriazine-3-carboxylates 4 (R1 = C02R2) were formulated as the 1,4-dihydro derivatives. Reduction of 1,2,4-benzotriazine A-oxides 5 affords 1,2,4-benzotriazines or dihydro-1, 2,4-benzotriazines, the product ratio depending on the conditions used346b 350a,b 374,375 (see Section 2.2.1.5.2.). 

From PM3 studies, the ring closure of 2-(aminocarbonyl)benzenediazonium ion to 3,4-dihydro-1,2,3-benzotriazin-4-one 3 has been proposed to proceed through an enol-type intermediate. A 6-NO2 group in the starting material is predicted to accelerate and a 6-MeO group to retard the cyclization <2001JMT(535)199>. 

Dihydro-l,2,3-benzotriazin-4-ols 20 are formed from 2-acylbenzenediazonium chlorides 52 and primary aliphatic amines see Scheme 6 for the scope of this transformation and relevant references. 

Under matrix isolation, liberation of N2 from 3,4-dihydro-l,2,3-benzotriazin-4-ones is not the only process that may be observed. Irradiation of 3-methoxy-3,4-dihydro-l,2,3-benzotriazin-4-one 19g (Ar matrix, 10 K, >300nm) resulted in photoreversible formation of ( /Z)-benzazetinones 85 (photo-interconvertible), while there was no firm indication of a ketene intermediate. Thus, a 1,3-sigmatropic shift of the C=0 group from N-3 to N-1 was proposed (Equation 12). A similar reaction was observed for the 3-butoxy- but not for the 3-methylbenzotriazinone 19f <1992CL361>. 

In contrast, alkylations of 3,4-dihydro-l,2,3-benzotriazin-4-ones occur almost exclusively at N-3, and, in recent years, several examples of this finding have been presented, increasingly with microwave activation. 3-Benzylated benzotriazinones 19o were prepared from 3 with the corresponding benzyl chlorides in dimethylformamide (DMF) (Equation 15) <1997JHC1391>. 

Both 3-amino- (and 3-substituted amino-) indazoles and 2-aminobenzanilides (or 2-aminobenzamidines) have been obtained from 3-benzyl-4-imino- and 3-methyl(or phenyl)-4-phenylimino-3,4-dihydro-l,2,3-benzotriazines upon treatment with N2H4/Ra-Ni <1970JC2308>. Electrochemical reduction of 3 in the presence of dilute H2SO4 and of 19n in EtOH/O.SM HCl gave good yields of indazolin-3-one (137 see Equation (50) <1976BSF433>. 

For the rearrangement of 3-substituted-3,4-dihydro-l,2,3-benzotriazin-4-imines 54 (R3 = Bn, Ar) to the isomeric 4-benzyl- (or aryl-) amino-1,2,3-benzotriazines 36, see Section 9.01.4.4. A substituent shift from N-2 to N-3 in 2-methyl- (2-aryl-) l,2,3-benzotriazin-2-ium-4-olates to give the 3-methyl- (3-aryl-) 3,4-dihydro-1,2,3-benzotriazin-4-ones by irradiation in acetonitrile has been reviewed previously <1984CHEC(3)369>. 

The use of 3-hydroxy-3,4-dihydro-l,2,3-benzotriazin-4-one (Dhbt-OH, 19d) as an additive in peptide synthesis by either the carbodiimide or active ester method, and the preparation of such esters from 9-Fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids and a method to prepare analogues of Dhbt-OH have been reviewed up to 1992 in CHEC-II(1996). Always crucial is the conservation of optical purity of the amino acid building blocks in amide or peptide synthesis, and addition of 19d is effective in conserving this optical purity. Both the formation of active esters from 19d and the suppression of racemization by 19d are regarded as due to the nucleophilic character of its anion <1970CB2024> see also Section 9.01.4.2. 

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