4//-l,2,4-Triazepine

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

Benzoyl-3,6,7-triphcnyl-2//-l,2,4-triazepine (35%) is obtained from benzoyl chloride and... 

RuCl(TAZO)(p-cymene) (TAZO =2-methyl-5-oxo-7-phenyl-3-thioxo-3,4,5, 6-tetrahydro-2//-l,2,4-triazepine TAZS =2-methyl-7-phenyl-3, 5-dithioxo-3,4, 5, 6-tetrahydro-2H-l, 2, 4-triaze-pine). These were made from [RuCljCp-cymene)] and (TAZO). As RuCl(TAZO)(p-cymene)/Oj/MejCHCHO/CH3Clj they epoxidised natural terpenic alkenes (Table 3.1) [959]. 

The reaction of (1 /. , 3/. , 5/. )-2-rncthyl-3,5-bis(rncthylthio)-7-phcnyl-2//-l, 2,4 triazepine 59 with trimethyloxosulfonium iodide 60 was described <2000MOL186>. This reaction is depicted in Scheme 4 and was performed under inert atmosphere using standard vacuum line techniques. Trimethyloxosulfonium iodide was suspended in anhydrous DMSO and sodium hydride was added at room temperature. The mixture was stirred and cooled to 10 °C before adding rapidly a solution of 59 in anhydrous DMSO. After stirring for 48 h at room temperature the reaction mixture was poured in cold water and extracted with chloroform. The product was identified as 2-methyl-5-methylmercapto-3-dimethylsulfoxymethine-7-phenyl-l,2,4-triazepine 61, which was obtained, in 85% yield, as an orange solid after recrystallization from carbon tetrachloride. 

Fully-unsaturated 2//-l,2,4-triazepines 690 are formed by the cycloaddition of 1-azirines 688 to 1,2,4,5-tetrazines 689 (Scheme 298). The initial product rearranges by a 1,5-hydrogen shift to give 690 <1974TL2303>. 

Thermolysis of 4-benzyl-3,7-diphenyl-4/7-l,2,4-triazepine gives a mixture of the rearranged pyrazole 2, 2.4-diphenylpyrimidine and l-benzyl-4-phenylimidazole.341... 

A solution of ethyl 5-amino-3-(2-pyridyl)-l//-l,2,4-triazepine-6-carboxylate 266 mg (1.0 mmol) in 0.2M NaOH (lOmL) was refluxed for 1 h. After cooling, the solution was neutralized with dil HCI, and the resulting precipitate was filtered and dried yield 162 mg (74%). Recrvstallization (DMF/MeOH) afforded a colorless powder mp >300 C. 

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). 

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). 

Theoretical calculations depicted in Section 13.14.2.1.1 (i) were complemented with experimental measurements of UV-Vis spectroscopy to determine which of the different tautomers of 3,5-dithio-2,7-dimethyl-[l,2,4]-triazepine 4 (Figure 1) are present in different solvents and ambient conditions <2005SAA875>. The results showed that in nonpolar solvents (MeCN), the most stable tautomeric forms seem to be the dithione form 4 followed by the isomers 6 and 7. The experimental spectrum showed three parts the first was located between 350 and 450 nm, log e 2.72 at 400 nm and log 3.37 at 360 nm, and appears to be composed of one or two mt bands. The second part of the spectrum located between 250 and 350 nm was a jtjt band, log e 4.46 at 290 nm. The third region below 250 nm was composed of two 7t7t bands located ca. 230 and 210nm, log s 3.92 at 230 nm and log s 4.17 at 210nm, respectively. 

The synthesis of diaryl-thiazolotriazepines 62 from the reaction of l,2,4-triazepine-3-thiones 63 (1.8 mmol) with 2-haloketones 64 (6.25 mmol) in ethanol under reflux for 2h was described <1999T5909> with the goal of creating new immunomodulating agents (Scheme 5). The starting triazepines were prepared by the addition of thiocyanic acid 65 to the chalcones 66 according to an already known method, followed by reaction of the intermediate 67 with hydrazine. 

The first example of the pyrazolo[l,5- ]-l,2,4-triazepine system 156 was obtained by reaction of l,5-diamino-3-f-butylpyrazole 157 with acetylacetone 158 in refluxing acetic acid <2003OBC4268> (Figure 8). The product was obtained as an oil (39%) after chromatography on alumina. 

Diaminopyrazoles 158 and 159 also react with /3-ketoesters in refluxing acetic acid (1-1.5 h) to give pyrazolo[l,5-A -l,2,4-triazepin-2-ones 160-163. Compounds 160-162 were prepared in 42—45% yield using the appropriate keto-esters, though ethyl benzoylacetate and ethyl pivaloylacetate failed to react, presumably by electronic and steric... 

The 4//-l,2,4-triazepine system 692 can be prepared via a photochemical rearrangement of 3,4,7-triaza-2,4-norcar-adienes 691 (Scheme 299) <1976TL2459>. 

Cyclization of 2,7-dimethyl-5-hydrazino-6 f-l, 2,4-triazepin-3-thione (552) with orthoesters gave [78JCR(S)190] 3-substituted 6,8-dimethyl-9//-l,2,4-triazepin-5-thiones 553. 

Trichloro-l,3-diphenyl-l/f-l,2,4-triazepine has recently been synthesized in high yield by the reaction of tetrachlorocyclopropene with two moles of diphenylnitrilimine (81S322). 

Aryl-l,2,4-triazepin-3-ones (2) were also prepared from the appropriate aryl isocyanate and 3-(methylamino)propionaldehyde diethyl acetal (Scheme 4). The yields in each reaction step were comparable to those for the synthesis of the triazin-3-ones. 

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