Whole-gunawardana-thesis.pdf (4.04 MB)
Synthesis of some benzoxaza and benzodioxaza heterocycles: Use of the Meisenheimer rearrangement route to fused medium-ring systems
thesisposted on 2023-05-27, 07:41 authored by Gunawardana, IWK
The aim of this work was to prepare examples of benzodioxazocine and benzodioxazonine ring systems by the Meisenheimer rearrangement of the N-oxides of related benzoxaza systems. The 1,4-benzoxazepine and 1,5-benzoxazocine derivatives required as starting materials were prepared by two different ring construction methods, viz. the Bischler-Napieralski cyclization and a C-N type condensation. For example, 8-methoxy-5-phenyl-2,3-dihydro-1,4- benzoxazepine was obtained by the Bischler-Napieralski cyclization of an amide precursor. Three other 1,4-benzoxazepine derivatives and 9-methoxy-6-phenyl-3,4-dihydro-2H-1,5-benzoxazocine were similarly prepared (Chapters 2 and 3). A C-N type ring construction method was employed to prepare 5-phenyl-2,3-dihydro-1,4-benzoxazepine and its 7-chloro analogue. In these cases the precursors were amino-ketones.All these cyclic imines were then converted to the corresponding N-methyl amines by quaternization and reduction. These amines were converted to their N-oxides for use in the Meisenheimer rearrangement. The Meisenheimer rearrangement of 1,4-benzoxazepine-N-oxides proceeded smoothly giving rise to the corresponding 1,5,4-benzodioxazocine derivatives in high yields. For example, 9-methoxy-4-methyl-6-phenyl- 3,4-dihydro-2H,6H-1,5,4-benzodioxazocine was prepared from 8-methoxy- 4-methyl-5-phenyl-2,3,4,5-tetrahydro-1,4-benzoxazepine-N-oxide. Five analogous 1,5,4-benzodioxazocines were similarly prepared (Chapter 4). However, when the 1,5-benzoxazocine-N-oxide derivative was subjected to this rearrangement at about 10¬¨‚àû, only decomposition products, including hydroxylamines, were obtained. At lower temperatures (-5¬¨‚àû-0¬¨‚àû) the Meisenheimer rearrangement of this N-oxide gave the expected ring enlarged product, 10-methoxy-5-methyl-7-phenyl-2,3,4,5-tetrahydro-7// 1,6,5-benzodioxazonine in 50% yield. The 1,5,4-benzodioxazocine and 1,6,5-benzodioxazonine ring systems have not been described previously.
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