1.4- Diazepine

The PdCli-catalyzed instantaneous rearrangement of A -carbethoxy-S-azabi-cyclo[5.1.0]oct-3-ene (60) takes place at room temperature to give A -car-bethoxy-8-azabicyclo[3.2.1]oct-2-ene (61)[50], The azepine 62 undergoes a smooth skeletal rearrangement to give 63, and the diazepine 64 is converted into the open-chain product[51]. Beckmann fission of the oxime 65 of ketones and aldehydes to give the nitrile 66 is induced by a Pd(0) complex and oxygen [52,53]. 

Table 4. Pyrrolopyrimidine, Diazepin, and Other A Nucleoside Antibiotics, Sugar-I -X...

DiaZepin Nucleosides. Four naturally occurring dia2epin nucleosides, coformycin (58), 2 -deoxycoformycin (59), adechlorin or 2 -chloro-2 -deoxycoformycin (60), and adecypenol (61), have been isolated (1—4,174,175). The biosynthesis of (59) and (60) have been reported to proceed from adenosine and C-1 of D-ribose (30,176,177). They are strong inhibitors of adenosine deaminase and AMP deaminase (178). Compound (58) protects adenosine and formycin (12) from deamination by adenosine deaminase. Advanced hairy cell leukemia has shown rapid response to (59) with or without a-or P-interferon treatment (179—187). In addition, (59) affects interleukin-2 production, receptor expression on human T-ceUs, DNA repair synthesis, immunosuppression, natural killer cell activity, and cytokine production (188—194). 

There are several examples of the formation of pyridazines from other heterocycles, such as azirines, furans, pyrroles, isoxazoles, pyrazoles or pyrans and by ring contraction of 1,2-diazepines. Their formation is mentioned in Section 2.12.6.3.2. 

Ring contraction and intramolecular cyclization constitute a convenient route to ring-fused systems that would be difficult to synthesize in other ways. H- 1,2-Diazepines (538) undergo electrocyclic ring closure to the fused pyrazole system (539) (71CC1022). Azepines also undergo similar valence bond isomerizations. 

The 1,2-diazepine ring system is related, thermally and photoehemieally, to two pyrazole [4.5] bicyclie systems (511) and (512). A large number of publieations by Moore, Sharp, Snieekus and Streith deal with these isomerizations (72CC827, 80CC444). 

Pyrazoles can be prepared by ring opening reactions of fused systems already containing the pyrazole nucleus. Thus several [5.5], [5.6] and [5.7] fused heterocycles have been opened to substituted pyrazoles, usually in basic medium. In general, the method has little preparative interest since another pyrazole derivative has usually been used to build the ring-fused system. However, due to the unexpected structures obtained, two publications are worthy of notice. 6//-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine (638) was readily obtained from the corresponding pyrazolopyrimidine by the action of diazomethane at room temperature (Scheme 59) (81H(15)265). When (638) was treated with potassium hydroxide, the pyrazole (640) was formed, probably via the diazepine (639). 

Tricarbonyliron complexes of 1,2-diazepines do not show the rapid isomerization found in their azepine counterparts (Scheme 22) the iron forms a diene complex with the C=C double bonds in the 4- and 6-positions. The chemistry of the 1,2-diazepine complexes is similar to that of the azepine complexes (Section 5.18.2.1) (81ACR348). 

Structural isomerization of three-membered rings with exocyclic unsaturation (Scheme 21) has been found with aziridineimines (Section 5.04.3.13) and diaziridineimines (Section 5.08.3.2.4). This involves an acyclic intermediate, while large ring systems prefer to isomerize through bicyclic ones. The 1,2- to 1,3-diazepine conversion is an example (Scheme 22) (Section 5.18.2.2). 

Photoisomerization of azomethinimines to diaziridines was observed in several classes of compound. Diazepine (271) was converted, even by sunlight, to its diaziridine isomer (68JA4738). Further photoisomerizations were observed with azomethinimines (272) obtained from pyrazolidones (70JPR161), and with some pyridazinium betaines (273). 

With munchnones, the initial adducts (330) spontaneously lose carbon dioxide with ring cleavage to give the benzo-l,3-diazepines (331) (81TH50901). 

H-1,2-Diazepine, 1 -acyl-3,5,7-triaryl-synthesis, 7, 602 If/-1,2-Diazepine, 2,3-dihydro-cycloaddition reactions, 7, 604 If/-1,2-Diazepine, 4,5-dihydro-synthesis, 7, 599 4//-1,2-Diazepine, 5,6-dihydro-synthesis, 7, 597, 598... 

Diazepines synthesis, 7, 595-620 transition metal complexes reactivity, 7, 28... 

Diazepines alkylation, 7, 617 electrophilic reactions, 7, 615 with fused heterocyclic rings... 

H-Dibenzo[d,/][l,3]diazepine, 5,7-dihydroxy-synthesis, 7, 605 Dibenzodiazepines synthesis, 7, 605... 

Pyrazolo[3,4-d][l,2]diazepines synthesis, 7, 597 Pyrazolop, 4- 6][ 1,4]diazepines synthesis, 5, 272 Pyrazolo[l, 4]diazepinones as anticonvulsant, 1, 170 Pyrazolo[2,3-e]diazepinones synthesis, 5, 272 1 H-Pyrazolo[l,5-6]imidazoles synthesis, 6, 992 Pyrazolo[2,3-a]imidazoles biological activity, 6, 1024 Pyrazolo[2,3-c]imidazoles reactions, 6, 1041 synthesis, 6, 1047 Pyrazolo[2,3-imidazoles synthesis, 6, 991 Pyrazolo[3,2- njisoquinolines synthesis, 5, 339 Pyrazolop, 4-c]isoquinolines synthesis, 5, 273 Pyrazolonaphthyri dines synthesis, 5, 339 Pyrazolone, diazophotolysis, 5, 252 Pyrazolone, 4,4-dihalo-rearrangements, 5, 250 Pyrazolone, ethoxy-hydrazinolysis, 5, 253 Pyrazolone, 4-halo-... 

---