2.4- Benzoxazocine

Chemical Name 3,4,5,6-tetrahydro-5-methyl-1-phenyl-1 H-2,5-benzoxazocine hydrochloride Common Name —... 

The enol lactones were synthesized by Hofmann degradation of metho salts of classic phthalideisoquinoline alkaloids. The biogenetically relevant transformations were highly stereospecific. In this way aobamidine (96) was obtained from the methiodide of (erythro) bicuculline (88) (2), and ad-lumidiceine enol lactone (97) was produced from both (threo) isomeric adlumidiceine (89) and capnoidine (90) methiodides (14,15,91-93). (Z)- (98) and ( )-N-methylhydrastine (99) were obtained from / - (91, erythro) and a-N-methylhydrastinium (92, threo) iodides (5,87,91,96-98), respectively, as were (Z)- (101) and (JE)-narceine enol lactones (102) synthesized from a- (94, erythro) and /J-narcotine (95, threo) quaternary N-metho salts (87,90), respectively. In a similar process /J-hydrastine (91) JV-oxide heated in chloroform yielded enol lactone 124 of Z configuration (99) however, a-narcotine (94) N-oxide was transformed to benzoxazocine 125 (99). ... 

There are many examples for seven-membered benzoannelated heterocycles that include benzazepines (332) [245, 454] benzothiazepines (333) [455, 456] and the very important pharmacological family of benzodiazepines (334) [285, 457, 458], which was the first class of small molecules synthesized on solid supports [459]. Benzoxazocines (335) [460] are examples for benzoannelated eight-mem-bered heterocycles obtained on solid supports (Fig. 3.14). 

Four oxazocine rings and 15 benzoxazocine systems are possible a compilation of the literature on these compounds has been prepared (82H(19)709). Many of these ring systems have been described in patents and rather obscure journals, and in a number of cases the evidence for structural assignments is inadequate. Methods of preparation include cyclization of polyfunctional chains, and ring expansions or rearrangement of several types. Some representative examples of oxazocines and benzoxazocines that have been well characterized are compounds (305)-(310). 

The transition metal catalysed nucleophilic attack of heteroatoms onto triple bonds has also been exploited in the preparation of larger rings. The intramolecular reaction of the phenol derivative shown in 5.12. and the pendant triple bond could result in the formation of a seven or an eight membered ring. Although the former system would be favoured by geometric considerations, the only product formed in the process is the benzoxazocin derivative, whose formation is probably driven by electronic factors.12... 

Phenyl-3,4,5,6-tetrahydro-lIA2,5-benzoxazocine hydrochloride [iV-desme-... 

REPRESENTATIVE EXAMPLES OF NMR STUDIES ON 2,5-BENZOXAZOCINE MEDIUM RING STEREOCHEMISTRY... 

Fig. 13. Crystallographically determined torsion angles (deg) and different orientations of the (reference,S)-TCC conformation for 1 -phenyl-3,4,5,6-tetrahydro-1 //-2,5-benzoxazocine-5-carbonitrile (30).

Racemic (1 / A,3RiS )-3-methyl-1-phenyl-3,4,5,6-tetrahydro-l//-2,5-benzoxazocine-5-carbonitrile (35) crystallized as a racemic compound in an achiral space group.1 X-ray structure analysis showed that one of the enantiomers in the crystal was bent into the (retro,S)-TBC conformation (for torsion angles of the X-ray structure, see Fig. 18).1 TBC is a relatively rare d.v-cyclooctene conformation, and is the fourth and highest energy conformation for d.v-cyclooctene within an energy window of 33.4 kJ from the ground state.1 Selected FI and 13C solution-state and 13C cp/mas... 

The synthesis of benzoxazocines 253a-f was performed by a solid-phase synthesis approach with a three-component reaction. Thus, 1,3-propylenediamine was attached onto a chlorotrityl polystyrene resin and condensed with aliphatic... 

Regarding the 1,3-oxazocines, it was reported that the isolation of 5, 8-anhydro-adenosine in an attempt of obtaining 8-fluoroadenosine <2007T3782>, a decaline-fused 1,3-oxazocine, which was unexpectedly obtained in the contest of an attempted synthesis of axinyssamine <2007T1544>, an efficient synthesis and X-ray crystal structure analysis of [ 1 ]bcnzopyrano[4,3-r/]l,3-benzoxazocin-13-onc and its derivatives and 5,6-dihydro-2,4-... 

The two step conversion of the benzoxazole, first into the benzoxazolium bromide 123 followed by ring expansion afforded the A-formyl benzoxazocine 124 (Scheme 13) <1995JOC2597>. This approach was also successfully applied to the synthesis of A-formyl benzo[l,4]thiazocine from the benzothiazole (Scheme 16, Section 14.06.5.3). 

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