Triazepine derivatives

Photolysis of pyridazine IV-ethoxycarbonylimide results in the formation of the pyrrole derivative (56). The rearrangement is postulated to proceed via a diaziridine, followed by ring expansion to the corresponding 1,2,3-triazepine derivative and rearrangement to a triazabicycloheptadiene, from which finally a molecule of nitrogen is eliminated (Scheme 19) (80CPB2676). 

Interesting triazepine derivatives have been prepared from silaheterocycles with CDI or ImCSIm. For the conversions via the various routes with about 70% yields were reported.11493... 

Imidazo-fused analogues 174 of the 1,2,4-triazepine system have been synthesised from pre-formed imidazoles 173. Reaction of 173 with iV,iV -dimethylhydrazine.2HCl and the appropriate orthoformate then resulted in the triazepine derivatives 174 the formation of the imidates 175 is proposed to occur initially, followed by the ring closed intermediates 176. Reaction of 176 with the alcohol would then give 174 <04JMC1044>. 

Pentacarbonyl(trichloromethylisocyanide)chrome (26) reacted with A,A -dimethylethylene-diamine to give the 1,3,5-triazepine derivative (28) via adduct (27) (Scheme 3) <88AG1391, 89JOM(369)105>. 

The reaction of 2-amino-l-pyrazolylbenzimidazole (69) with 1,2-dibromoethane in the presence of potassium carbonate yielded the substitution product (70), which then immediately cyclized to afford the benzimidazo[l,2-c]pyrazolo[2,3-a]-l,3,5-triazepine derivative (71) (Scheme 12) <94BSB57>. 

Ring closure reactions of a 4-hydrazino[l]benzofuro[2,3- /]pyridazine, derived from naturally occurring rotenone, yielded [l]benzofuro[2,3-d]pyridazines fused with 1,2,4-triazole, 1,2,4-triazine, and 1,2,4-triazepine derivatives <01JHC1097>. 

Derivatives or benzo analogs of all four possible 1//-triazepine systems are known. 

Triphenyl-2//-l,2,4-triazepine reacts with tosyl chloride under standard conditions to afford the 2-tosyl derivative 20.337... 

Azido-3-methoxypyridazines 1 are transformed into 6,7-dimethoxy-477-1,2.5-triazepines 3 by irradiation in the presence of sodium methoxide. The reaction proceeds via the unstable 277-tautomers 2, which were detected by NMR spectroscopy and can be trapped as the 2-acetyl derivatives 4 by adding acetyl chloride to the crude photolysate.371 The synthesis fails for azidopyridazines lacking the 3-methoxy substituent. 

A light-induced ring expansion of the tetrazolo-uracil 147 afforded ready access to the ring expanded 57f-l,3,5-triazepine-2,4-dione nucleoside derivative 148 in 80% yield <06JOC1742>. 

Phenylsydnone 89 is not restricted to [3+2] cycloaddition. Reaction of sydnone 89 and its derivatives with the substituted azete 90 gives isomeric l//-triazepines after extrusion of carbon dioxide (Equation 8). 

The N—C—N—N fragment can also be supplied by thiosemicarbazides (NH2N(R)CSNH2) which react with malonic acid derivatives or j8-keto esters to give l,2,4-triazepine-3-thiones (78JHC71, 80RTC301). 

Another interesting reaction of diamines with isothiocyanates is the formation of l,3,5-triazepine-2-thione derivatives by the action of various classes of diamines on 2,3,4,5,6-penta-O-acetyl-D-gluconyl isothiocyanate (32). The reaction has been performed in acetonitrile or N,N-dimethyl-formamide solution with o-phenylenediamine, diaminomalononitrile, 5,6-diamino-l,3-dimethyluracil, 4,5-diamino-2,6-dithiopyrimidine, 4,5-diamino-2-thiopyrimidine, and 4,5-diaminopyrimidine, and afforded... 

The gas-phase basicity (GB) of 3-thio-5-oxo 1, 5-thio-3-oxo 2, and 3,5-dithio 4 derivatives of 2,7-dimethyl-[l,2,4]-triazepine (Figure 1) has been measured by means of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and complemented with theoretical calculations. The experimental FTICR results are discussed in Section 13.14.4.1.l(i). The structures and vibrational frequencies of all stable protonated tautomers and all transition states connecting them have been obtained by means of the B3LPY density functional method, together with 6-31G basis set expansion. The final energies were obtained at the B3LYP/6-311 + G(3df,-2p) level (2002JPC7383). 

Reactions of 1,2-diaminobenzimidazole 72 with 1,3-diketones, acetocetic acid, and its derivatives to obtain fused triazepines were studied <2002CHE598>. The obtained products are depicted in Scheme 18. 

In the synthesis of l,2,5-triazepine-l,5-diones, which are expected to mimic the structural features of or-peptidyl prolin-amides, the preparation of N2,N3-disubstituted derivatives 213a from the reaction of (Z)-alanine with the N2-substituted triazepines 213 resulted in lower yields. It has been reported that these fused triazepinediones could be elaborated to give constrained rir-peptidyl proline peptide mimetics of defined stereochemistry and sequence <1997J(P1)2297>. 

All the approaches discussed in Sections 13.16.9 and 13.16.10 were widely applied to the synthesis of 1,3,5-triazepine heterocyclic ring. For the monocyclic and fused compounds, the [1+6] and [3+4] cyclization reaction and the azine ring expansion are the most popular routes (for additional information on the early reports, see CHEC-II(1996)). The bridged derivatives, such as hexaazaisowurtzitanes 5 (Figure 1), are available by multicomponent condensation. 

In our opinion, the reactions of chalcones 141 with some or /zo-diamines containing a hydrazine amino group (1,2-diaminobenzimidazole 142, 3,4-diaminotriazoles 143 and 1,2,4-triaminotriazoles 144) [122, 123, 124] are more interesting from both a practical and a theoretical viewpoint. The possibility to obtain the derivatives of azolopyrimidine 145—147 but not the triazepine systems in such reactions was demonstrated [124]. In this case the cyclocondensation is accompanied by the elimination of not only a molecule of water but also a molecule of ammonia. The proposed mechanism of the cyclocondensation [122] implies formation of a dihydroazolopyrimidine system with its subsequent heteroaromatization by amino-group elimination (Scheme 4.45). 

The photolysis of 4-azidopyridazines gives significant yields of the ring-expansion products, unsaturated 1,2,5-triaze-pines. Thus, 3-methoxy derivative 801 reacts, via formation of a nitrene and ring opening of an intermediate fused azirine, with methoxide or diethylamine to give 4-methoxy (or4-diethylamino)-l,2,5-triazepines 802 (X = OMe, NEt2). 

The triazepine dione derivatives 94 (R, R, R, R = H, alkyl groups) have neurotrophic activity and are potentially useful in the treatment and prevention of neuronal disorders including, for example, Parkinson s disease, Alzheimer s disease and multiple sclerosis <03WOP028734>. 

Diazepines were also transformed into pyridazines either with hydrochloric acid, NBS, or hydrazine (77BCJ2153 86H3059). A 1,2,5-triazepine could also be transformed into a pyridazine derivative (85H1675). 

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