Oxazepines and Thiazepines

Oxazepines and Thiazepines.—The irradiation of quinoline N-oxide (168) has been assumed to give the 3,1-benzoxazepine (169) as the primary product, but in earlier work only the hydrolysis products iV-formylindole and iV-formyl-2-hydroxyindoline were obtained. In a re-investigation of the photolysis, carried out under scrupulously anhydrous conditions, the parent benzoxazepine has been obtained for the first time. Under the same conditions, isoquinoline N-oxide gave the non-isolable 1,3-benzoxazepine (170), which could be identified spectroscopically in dilute solution and trapped by the addition of amines, but which polymerized when concentrated.  

An analogous reaction forms the key step in a direct and versatile route to 4-substituted indoles from quinoline N-oxides. Irradiation of the latter gave (171 X = H), which was hydrolysed by chromatography on silica to give the indolinol (172) this was transformed into (173). The benzoxazepines (171) are stable solids when X = CN, but they rearranged if irradiated (254 nm) to give the 3-formylindole (174) [cf. the analogous reactions of diazepines and oxepines described above]. 

2-Oxazepines have previously been suggested as unstable intermediates in the photolysis of acridine N-oxide and related N-oxides now two examples, (175 R = CN) and (175 R = Cl), have been isolated for the first time. As predicted, they are unstable and undergo a variety of isomerization reactions in the dark and under mild conditions. The novel cyclic sulphilimine (176) ring-expands when boiled in xylene to give the dibenzothiazepine (177) in moderate (26%) yield.  

Earlier work on the use of C,N-dilithiated intermediates in the synthesis of phenanthridenes has now been extended to the seven-membered dibenzo- 

Kaneko, A. Yamamoto, and M. Hashiba, Chem. Pharm. Bull, 1979, 27, 946. 

---

Psycholeptics, Diazepines, Oxazepine and Thiazepines (clozapine, quetiapine, olanzapine)... 

There has been a modest interest in the chemistry of these systems over the past decade. In this chapter, the 1,2-oxazepines and 1,2-thiazepines are grouped together due to their sparseness in the literature. There is a general review of these systems that appeared in CHEC-II(1996) <1996CHEC-II(9)183>. The parent systems 1 and 2, respectively, are shown below however, most of the known compounds are based on their reduced derivatives. Oxidized forms of the 1,2-thiazepine system are also treated, in particular derivatives of 1,2-thiazepine 1,1-dioxide 3. 

Compared with azepine derivatives, considerable scope still exists for innovative exploration of ring-closing metathesis methodology to access multisubstituted 1,2-oxazepine and 1,3-thiazepine derivatives and benz-fused analogues. Also, the full synthetic potential of the Meisenheimer rearrangement to afford various 1,2-oxazepine derivatives with different types of functionality present is still to be realized. 

Considerable synthetic scope exists for the application of diene-based and ene-yne-based ring-closing metathesis reactions to the synthesis of 1,3-oxazepine and 1,3-thiazepine derivatives. Particular emphasis on type e reactions is likely to be very fruitful. 

Ring Synthesis of 1,4-Oxazepines and 1,4-Thiazepines, Classified by Number of Ring... 

---