Diazepines as Substrates

Treatment of l,3-diphenyl-4,5,6,7-tetrahydro-l//-l,2-diazepine (32) with polyphosphoric acid at 110°C for a few minutes gave three products, of which one proved to be 2,5-bis(3-anilinopropyl)-3,6-diphcnylpyr tzine (33) (10% yield after separation) a rational mechanism involving N—N fission and subsequent dimerization has been proposed No other examples appear to have been reported. 

Flash pyrolysis of 5,7-diphenyl-2,3-dihydro-17/-l,4-diazepine (34, R = H) at 700°C in a vacuum afforded 2-phenylpyrazine (35) in 21% yield, after separation from a pyrimidine the methyl substrate (34, R = Me) also gave a small yield of the same product (35) and 6-phenyl-2,3-dihydro-17f-l,4-diazepine gave some unsubstituted pyrazine.  

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Stanovnik and co-workers (100,101) systematically investigated the cycloaddition reactions of diazoalkanes with unsaturated nitrogen heterocycles, such as azolo-[l,5-fl]pyridines, pyridazin-3(2/7)-ones, and [fo]-fused azolo- and azinopyridazines. The Stanovnik group have studied the further transformations of the products and reviews of this chemistry are available. In a typical example, the reaction of 6-chlorotetrazolo[l,5-/7]pyridazine (37) with 2-diazopropane yields the NH,NH-dihy-dro-pyrazolo[4,3-(i]tetrazolo[l,5-/7]pyridazine 38 (102) (Scheme 8.11). The latter substrate reacts with acetone to produce an azomethine imine 39 that thermally rearranges to give the fused dihydro-1,2-diazepine 40. The azomethine imine obtained with glucose can be trapped with methyl acrylate to furnish the C-nucleoside 41 (103). 

The incorporation of an amide bond in the substrate provided l,4-diazepin-2-ones as single diastereomers with the stereochemistry at C-5 determined by single crystal X-ray structure analysis, as depicted in Scheme 46 <2006OL3425>. 

With the aim of determining if similar reactivity could be displayed with maleimides using nonalkene substrates, the same authors have discovered a new photochemically mediated intramolecular [5+2] photocycloaddition of maleimides to C=N bonds [94]. Indeed, introducing a C=N based functionality to the maleimide photosubstrates 88 had the potential to extend the scope of the [5+2] cycloaddition by enabling the formation of 1,3-diazepines 89, constituting a class of diazepines that has rarely been reported. As shown in Scheme 20.38, the reaction performed in acetonitrile was tolerant to a wide range of C=N systems, and proceeded efficiently even with bulky substituted hydrazones and oximes. This process constituted a new method for the synthesis of fused polycyclic 1,3-diazepines. 

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