|dc.description.abstract||This research was directed towards the investigation
and development of an aryne route to the syntheses of
aporphi ne and dibenzopyrrocolinium (dibenzoindolizinium)
alkaloids and to the stability of the latter under the
conditions used for aryne formation. The work c an be
divided into three main sections .
i) - Synthesis of Glaucine
6-Bromo-3,4-dimethoxyphenylacetic acid, prepared by
the action of bromine i n acetic acid on3,4-dimethoxyphenylacetic
a cid, was converted into its acid chloride by t he
action of thionyl chloride. This on treatment with 3,4-
dimethoxyphenylethylamine pr ovided N-(3, 4-dimethoxyphenylethyl)-
2-(2-bromo-4,S-dimethoxyphenyl)-acetamide which on
dehydration with phosphoryl chloride (Bischler Napieralski
reaction) in dry benzene afforded l -(2-bromo-4,S-dimethoxybenzyl)-
3,4-dihydro-6,7-dimethoxyisoquinoline, isolated as
hydrochl oride. A new method o f destroying the excess of
phosphoryl chloride was developed which proved to be quite
useful. Methylation of the dihydroisoquinoline'with methyl
iodide in methanol , and subsequent reduction with sodium
borohydride provided (±)-6-bromolaudanosine. Act ion of
potassamide or sodamide in anhydrous liquid ammonia on
(±)-6-bromolaudanosine yielded the corresponding amino
derivative along with other products. Diazotization and
ring closure of (±)-6-aminolaudanosine then a f forded (±)-glaucine which was isolated as methiodide.
ii) - Intramolecular Capture of Aryne During Glaucine
Synthesis, and Subsequent Reactions .
This section deals with the by-products formed under
the conditions of the aryne stage of t he glaucine synthesis.
The crude product, obtained in the reaction of potassamide
or sodamide in liquid ammonia on (±)-6-bromolaudanosine, was
s eparated by chromatography, Three products were separated
a ) - 5,6-Dimethoxy-2-( 3,4-dimethoxy-6-ethylphenyl)-lmethylindole.
Two mechanisms are proposed for the formation
of this interesting product. This compound also was prepared
by the action of potassamide in l,iquid ammonia on 5,6 ,l2,l2atetrahydro-
i odide .
b) - 5,6-Dimethoxy-2-(3,4-dimethoxy-6-vinylphenyl)-lmethylindoline.
Its formation represented a new method
of Hofmann degradation . Further confirmation of structure
was done by performing the normal Hofmann reaction on
5, 6,12,12a-tetrahydro -2/3,9,lO-tetramethoxy ~7-methyldibe nz[
b,g]indolizinium iodide. The indoline prepared i n this way
was identical in all respects with that prepared above .
c) - 1- (2-amino-4,5-dimethoxybenzyl ) -l,2,3,4-tetrahydro-2-
methyl-6,7-dimethoxyisoquinoline, was converted t o glaucine
as stated in section 1 .
iii) - Attempt:,ed Sxnthesis of Liriodenine
Piperonal was converted into 3,4-methylenedioxyinitrostyrene which on reduction with lithium aluminium hydride
provided 3,4-methylenedioxyphenylethylamine. The method of
extraction after the reduction was improved t o some extent.
The amine on condensation with m-chlorophenylacetyl chloride,
prepared by the action of oxalyl chloride on 3,4-methylenedioxyphenylacetic
acid, provided N-[ ~ -(3,4-methylenedioxyphenyl)-
e thyl)-3-chlorophenylacetamide. This on dehydration
with phosphoryl chloride in dry benzene followed by air
oxidation afforded l-(3-chlorobenzoyl)-6,7-methylenedioxyi
soquinoline. This compound on r eaction with potassamide
in liquid ammonia afforded a crude product from which. one
product was separated by chromatography i n a pure condition .
This yellow compound analysed as,c17Hl ON2021 and was t he
main product i n the reaction ; a t entative structure is
A second compound, not obtained in pure condition,
was submitted to Pschorr reaction in the hope of obtaining
liriodenine, but without success.||en_US