1.2- Diazepines. rearrangement

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]. 

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-... 

Triphenyl-47/-l,2-diazepine is transformed into a mixture of 2,4,6-triphenylpyridine and the rearranged diazepines 3,5,6-triphenyl-4//-l,2-diazepine (28) and 3,5,6-triphenyl-l H-, 2-di-azepine (29) on prolonged heating.111... 

The diazepine 26 reacts with the stable nitrile oxide 27 to yield the cycloadduct 28, accompanied by a trace of the rearranged adduct 29.102... 

The Diels-Alder reaction of cyclopropenes with 1,2,4,5-tetrazines (see Vol.E9c, p 904), a reaction with inverse electron demand, gives isolable 3,4-diazanorcaradienes 1, which are converted into 4H-1,2-diazepines 2 on heating. The transformation involves a symmetry allowed [1,5] sigmatropic shift of one of the bonds of the three-membered ring, a so-called walk rearrangement , followed by valence isomerization.106,107... 

Cyclizations of doubly unsaturated diazo compounds containing a thiophene ring within rather than at the end of the diene system to yield thicnodiazepines have also been reported. Thus, thermolysis of the sodium salt 7 gives the l//-thieno[3,2-r/]-2,3-diazepine 9. The intermediate 8 rearranges to the more stable product 9 by a symmetry allowed [1,5] shift of hydrogen.14,1... 

Ethyl l//-l,2-diazepine-l-carboxylates 5 (Section 4.1.3.1.1.1.2.) rearrange to 1/7-1,3-diazepines 6 in refluxing xylene.157 The reaction only succeeds with 1,2-diazepines containing methyl groups in the 4- and/or 6-positions 3-, 5- or 7-substituted 1,2-diazepines do not isomerize to 1,3-diazepines. The products are very sensitive to hydrolysis so that chromatography has to be performed on Sephadex. 

A mixture of ethyl 3,5-dimethyl-l/f-thieno[2,3-c]-1,2-diazepine-l-carboxylate (6) (10-15%) and the isomeric ethyl 2,5-dimethyl-3//-thieno[2,3-t/]-l, 3-diazepine-3-carboxylate (8) (50-60%) is obtained when a solution of the thienopyridine A-iminc 4 in benzene is irradiated with a 400-W high-pressure mercury lamp for 2-3 hours at 20rC. It has been suggested that product 6 is formed from the intermediate 5. The isomeric intermediate 7 undergoes two consecutive walk rearrangements, followed by valence tautomerization, to give the major product 8.168... 

Dibenzo[l,3]diazepines 9, together with amidines and benzimidazoles, are produced by a rearrangement reaction when certain A.A -diarylamide oximes 7 are treated with tosyl chloride. The intermediate 0-tosyl derivatives 8 cannot be isolated.176... 

Another dihydro derivative has been described in connection with medicinal chemical studies. Thus, reaction of 2-(chloromethyl)quinazoline-3-oxide (3) with hydrazine gives hydr-oxytriazocinamine 4 (and not a diazepine derivative as originally assigned), vigorous acetylation of which results in a rearrangement to give oxazolotriazocine 5.10... 

The formation of 1-aminopyridinium chloride has been accomplished by the acid hydrolysis of N- ( -acetaminobenzene-sulfonimido)pyridine.4 Also, the rearrangement of a substituted diazepine has been observed to give a 1-aminopyridine derivative.5 The present procedure is an adaptation of that described by GosI and Meuwsen.1... 

Continuing his studies on the metallation of tetrahydro-2-benzazepine formamidines, Meyers has now shown that the previously unsuccessful deprotonation of 1-alkyl derivatives can be achieved with sec-butyllithium at -40 °C <96H(42)475>. In this way 1,1-dialkylated derivatives are now accessible. The preparation of 3//-benzazepines by chemical oxidation of 2,5- and 2,3-dihydro-l/f-l-benzazepines has been reported <96T4423>. 3Af-Diazepines are also formed by rearrangement of the 5//-tautomers which had been previously reported to be the products of electrochemical oxidation of 2,5-dihydro-lAf-l-benzazepine <95T9611>. The synthesis and radical trapping activities of a number of benzazepine derived nitrones have been reported <96T6519, 96JBC3097>. 

The ylide 44, prepared from the corresponding diazine and tetracyanoethylene oxide, rearranges in methanol the give the 1,3-diazepine 45 <96TL1587>. The x-ray geometry for 45 is reported. 

The photoreactions of four-membered nitrogen containing heterocycles have been less well investigated and meaningful results are confined to certain azetidines and azetidinones. The photochemically induced rearrangement of azetines 148 to 1,4-diazepines 149 has been rationalized in terms of a process equivalent to a di-7t-methane rearrangement116 a more... 

Although highly reactive, 2/7-azirines are of considerable synthetic interest and serve as a source of the 3-fluoro-4//-l, 3-diazepines 86. Reaction of 80 with difluorocarbene in the presence of furfural gave 86, rather than the expected furfural-derived products 83. Rearrangement of the initial 1,3-dipolar intermediate 81 to 84 and then cycloaddition of 84 with 80 are proposed as key steps in the reaction the intermediate cycloadduct 85 gave 86 on base-induced elimination of HF. Nucleophilic displacement of the fluoro group in 86 provided access to further substituted 1,3-diazepines <06TL639>. 

A high yield approach to the hexahydropyrrolo[3,2-e [l,4]diazepine-2,5-diones, 105 and their tetrahydrofuro analogues, 106, based on rearrangements of cyclopropylketimines and the cyclopropylketones, derived by acid hydrolysis, have been described. Thermolysis followed by DDQ oxidation of the unstable dihydro intermediates then gave compounds 105 (eg. R1 = Me, R2 = i-Bu) and 106 (eg. R = 4-Cl(C6H4)CH2) . 

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). 

Irradiation of the caged oxadiazabicyclo[2.23]nonadiene derivative 24 (X = CH) brings about its rearrangement to the isomeric system 25 and the formation of the 1-ethoxycatbonyl-l//-azepine (26) <99H(51)141>. The latter is also the product of irradiation 25, but the authors interpret their kinetic results to suggest that the azepine is not derived solely from 25, but is also formed directly from 24. Similar studies with 24 (X = N) give 1-ethoxycarbonyl-l// l,2-diazepine (Scheme 4). 

Various diazepines undergo rearrangement on treatment with concentrated hydrobromic acid to give naphthyr-idines in one step (Scheme 67) <2002TL1583>. 

Oxazepine chemistry includes some interesting rearrangement reactions both in synthesis and reactivity, many of which have parallels in the chemistry of the analogous diazepine systems. The preparative routes are classified as discussed earlier (p. 595). 

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