Dibenzo oxepines

The central C-C double bond of dibenz[, /]oxepin displays the properties of an activated aromatic system and undergoes substitution reactions. Nitration and acid-catalyzed dcutcration gives the dibenzo[i>,/]oxepins 1 with the respective substituent in position 10.161... 

Kiyama, R., Honma, T., Hayashi, K., Ogawa, M., Hara, M., Fujimoto, M., and Fujishita, T. Angiotensin II receptor antagonists. Design, synthesis, and in vitro evaluation of dibenzo[a,d]cycloheptene and dibenzo[b,f oxepin derivatives. 

Bromobenzyloxy)benzaldehyde 0-alkyloximes 383 are converted to the corresponding dibenzo[l), e]oxepines 384 by radical addition reaction with BusSnH and AIBN (equation 167)34 . 

The monocyclic thiepins are less stable than the corresponding oxepins and the few known examples have to date no significant commercial applications. Several members of the much more stable dibenzo[6,/]thiepin series have however been synthesized and tested for biological activity. Thus thiepins (259) and (260) were found to have antiinflammatory and antihistamine properties respectively (74JHC17). 

Aminomethyl)biphenyl-2-carboxylic acid (70) and -acetic acid (69) have been prepared from dibenzo-substituted oxepin-2-one 66 by potassium phthalimide ring opening. Further Arndt-Eistert homologation of 67 provided 68.[104]... 

V,/V-Dimethylaminomethyl-2,3,3 ,12 -tetrahydrodibenzo[A/]furo[2,3- /]oxepine derivatives, for example, 145 (X = F, Cl, Br, OMe, etc.), are described as potent anxiolytic agents <2004CPB262, 2005BML2898, 2005FA241>, dibenzo[A/]thieno[2,3- /]oxepine derivatives are claimed as inhibitors of tumor necrosis factor-cr and interleukin-1 production for the treatment of inflammatory diseases <2004W02004078763>. 8-Oxa-l,2-diazadibenzo[i , ]azulene derivatives (dibenzo[/>,/]pyrazolo[3,4- /]oxepines) were synthesized as inhibitors of tumor necrosis factor-x and interleukin-1 production <2003W02003099822>. 

Bauhinoxepins A and B, new antimycobacterial dibenzo[A,/]oxepines, were isolated from the roots of Bauhinia saccocalyx <2004HCA175>. 

A preparation of dibenz[A/]oxepinecarboxamide derivatives, useful for the treatment of neurological and vascular disorders related to /3-amyloid generation and aggregation, was claimed <2005W02005014517>. Closely related aminoalkyl-substituted dibenzo[A/]oxepine derivatives, for example, 149, are opioid receptor antagonists <2005W02005090337>. 

Reaction of 117/-dibenzo[7/]thiepin-10-ones 135a and 135b with chloroacetone in the presence of base in dimethyl sulfoxide (DMSO) resulted in formation of O-alkylation products 136a and 136b in 23% and 8% yields, respectively (Equation 18) <2006JHC749>. On the other hand, oxepine analogs preferentially gave G-alkylation products. 

The synthesis of the highly hindered dibenzo[c,e]oxepine derivative 153 has been achieved by acid-catalysed dehydration of the diol 152 [02JCS(P1)2673],... 

Novel classes of fused pyrroles, dibenzo[2,3 6,7]oxepino[4,5- ]pyrroles and dibenzo[2,3 6,7]thiepino[4,5- ]pyrroles, were prepared by the intermolecular cyclocondenation of dibenzo[2,3 6,7]oxepin-5-ones and dibenzo[2,3 6,7]thiopin-5-ones with (dimethylhydrazono)acetaldehyde <07JHC1129>. 

Chloro-10,ll-dibenzo[b,f]oxepin-10-yl)-8-methyl-3,8-diazabicyclo[3.2.1]octane... 

Treatment of ketone 409 with lithium diisopropylamide (LDA) results in the ethyl 1,2-dihydroxybenzoate 410 in a 74% yield (equation 191) . The acid-catalyzed isomerization of diarene oxides derived from benz[a]anthracene, chrysene and benzo[c]phenanthrene gives mixtures of isomeric polycyclic phenols. Finally, it should be mentioned that dibenzo[i>, ]oxepin 411 undergoes an interesting rearrangement to 2-hydroxyphenylindene 412 (equation 192). 

Dibenzo[h./]oxepins and dibenzo[hJ]thiepins have important medicinal uses and can be prepared by irradiation of halogeno-substituted acetophones in liquid ammonia in the presence of bases (Nagaoka). A novel 1,9-hydrogen atom abstraction occurs on irradiation of 47 to give ultimately the keto ether 48 (Mizuno et al.) and previously unknown polycyclic ring systems such as 49,... 

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