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Abstract

Efficient methods for the preparation of 3-keto-3,4-dihydro-2H-1,5-benzodioxepin (I, R1 = R2= R3= R4= H) have been developed.

This compound was then used as an intermediate for the synthesis of a series of derivatives of potential pharmacological interest. These were submitted to biological screening and preliminary results revealed that one of these compounds possessed weak tranquillising and antidepressant activity. However, this aspect of the work was abandoned at an early stage owing to the publication of patents ei.4 claiming biological activity for a variety of dihydro-1,5-benzo- Gdioxepins.

Attention was then focussed on the preparation of a series of ketones of the general formula (1) having from one to four t-butyl, methyl or pheny] substituents in the aromatic ring in order to study their chemical and physical properties and if possible to correlate these with the conformations of the heterocyclic rings.

Most of the substituted pyrocatechols (II) required as starting materials in this investigation were prepared by established procedures; marked improvements were made in the preparations of 3-t-butyl, 3,4,5- and 3,4,6-trimethylpyrocatechols.

The conversion of the pyrocatechols (II) into the substituted o-phenylenedioxydiacetonitriles (III) was accompanied in a number of cases by the formation of the symmetrical triazines.

Intramolecular cyclisation of the dinitriles (III) gave high yields of the enaminonitriles of the general formulae (V) and (VI).

Those derived from unsymmetrically substituted dinitriles were shown by nuclear magnetic resonance spectroscopy to be approximately 1:1 mixtures of the two possible isomers (V and VI). From a mixture containing the 6- and 9-methyl compounds (V, R1 = Me= R2= R3= R4 = H, R3= Me, R4= H) one pure isomer was separated and identified on the basis of its nuclear magnetic resonance spectrum.

Acid hydrolysis of the enaminonitriles (V) gave the corresponding ketones (I) which were characterised by chemical and physical methods.

Attempts were made to determine the conformation of the heterocyclic ring of the substituted ketonee (I) end their derivatives from the extent of their ultra-violet absorption in the 260-270nm band compsred with those of the correspondingly substituted planar 1,3 benzodioxoies (VII), as described by Archer and Claret3.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science > Q Science (General) Q Science > QD Chemistry
Departments:	School of Science & Technology > School of Science & Technology Doctoral Theses Doctoral Theses

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