METHODE DE PREPARATION DE DIENONES DE TYPE NARWEDINE ET DE LEURS DERIVES

METHOD FOR THE PREPARATION OF NARWEDINE-TYPE DIENONES AND THEIR DERIVATIVES

Abrégé anglais

ABSTRACT OF THE DISCLOSURE:
The present invention relates to a method for
the preparation of
< IMG > wherein A < IMG >
denotes
R3 is a halogen atom, R4 is a lower alkyl group, R5 is
HClO4 or other organic or inorganic acid;
X = O, Y = H2 or X = H2, Y = O or X = H2, Y = H2
wherein diphenolic compounds of the general formula:
< IMG >
wherein R3 and A have the above-mentioned meanings; and
R1 and R2 are,independently,each a lower alkyl group ,
a -CH2C6H5 group or a -CH2C6H4OCH3 group, are subjected to
electrochemical oxidation at an anode potential ranging from
1.1 to 1.7 volts in the presence of an organic solvent and a conductive

salt. The so obtained narwedine-type dienones are of high
purity and can give Amaryllidaceae alkaloids by subsequent
chemical transformations.

Revendications

The embodiments of the invention in which an
exclusive property or privilege is claimed are defined as
follows:
1. Method for the preparation of narwedine-type
enones and their derivatives of the general formula:
< IMG > wherein A < IMG >
denotes
R3 is a halogen atom, R4 is a lower alkyl group, R5 is
an organic or inorganic acid;
X = O ,Y = H2 or X = H2 , Y = O or X = H2 , Y = H2
characterized in that a diphenolic compound of the general formula:
< IMG >
wherein R3 and A have the above-mentioned meanings; and
R1 and R2 are,independently,each a lower alkyl group,
a -CH2C6H5 group or a -CH2C6H4OCH3 group, is subjected to
electrochemical oxidation at an anode potential ranging from
1.1 to 1.7 volts in the presence of an organic solvent
and a conductive salt.

2, Method as claimed in claim 1, wherein the
said solvent is methyl cyanate.
3. Method as claimed in claim 1, wherein the
said conductive salt is selected from the group constituted
by KClO4, LiClO4, (C4H9)4NBF4,and (C2H5)4NBF4.
4. Method as claimed in claim 1, wherein R5
is HClO4.
5. Method for the preparation of narwedine-type
enones and their derivatives of the general formula:
< IMG >
R3 is a halogen atom, R4 is a lower alkyl group ,
X = O, Y = H2 or X = H2, Y = O or X = H2, Y = H2
characterized in that a diphenolic compound of the general
formula:
< IMG >

wherein R3, X and Y have the above-mentioned meanings;
and R1 and R2 are, independently, each a lower alkyl
group, a -CH2C6H5 group or a -CH2C6H4OCH3 group, is
subjected to electrochemical oxidation at an anode
potential ranging from 1.1 to 1.7 volts in the presence
of an organic solvent and a conductive salt.
6. Method as claimed in claim 5, wherein the
said solvent is methyl cyanate.
7. Method as claimed in claimed 5 or 6, wherein
the said conductive salt is selected from the group
constituted by KClO4, LiClO4, (C4H9)4NBF4, and (C2H5)4
NBF4.
8. Method as claimed in claim 5, wherein R3 is
a bromine atom, R4 is a methyl group, R2 is methyl group,
a -CH2C6H5 group or a -CH2C6H4OCH3 group and R1 is a
methyl group, a -CH2C6H5 group or a -CH2C6H4OCH3 group.

Description

87 ~
Thl6 lnvention r~late~ to ~ method for the
preparation of narwedln~ type di~none~, which ~re the
starting ~ater~al~ for the ~ynthe6i6 of ~maryllidaceae
alkaloid~.
The preparation o~- narwedine-type dienone~ by
~henolic oxidative reaction6 ~ the appropriate diphenollc
derivatives is well known ln the literature, but by this
way of ox~dation a yreat number of by products which are
unusable and difficult to ~parate i~ produced.
The object of the lnvention is to provide a
method for the preparation ~f high purity narwedine-type
dienones with a g~od yiPld which can ~ive Amaryllidaceae
alkaloids by subsequent chamical transformations.
In accordance with the method of the present
invention the compounds of general formula
in which A 1~ R4 1~ 4 . R5
~ ~A denotes
0~
; H3C R3
R3 is a halogen atom, R4 is a lower alkyl group, R5 is HC104
: or other organic or inorganic acid
X = 0 ,Y = H2 or X = M~, Y = 0 or X = H2 ~Y = H2
are produced from di~henolic de~ivatives with co~non
formula:

17~3~
ORl X X
J~ 1
~ N-R4 ~ 4 5
R20 ~ ~ in wh ch A
~1 ,1
/\/ \
H3C0 3
Rl is a lower alkyl group, a ~CH2C6H5 group or a
-CH2C6H40CH3 group, R2 is a lower alkyl group, a CH~C~H5
yroup or a -CH2C6H50CH3 group, R3 is a halogen atom, R4
is a lower alkyl group, R5 is HC104 or other organic or
inorganic acid, X = H2, Y = O or X = O, Y = H2 or X = H2,
Y = H2 subjected to electrochemical oxidation at an anode
potential ranging from 1.1 to 1.7 volts in the presence
of an organic solvent and a conductive salt.
The electrochemical oxidation of the diphenolic
derivatives is performed in an electrolytic cell with
separated anode and cathode compartments, in an organic
solvent medium (e.g. methyl cyanate3, containing a conductive
salt (e.g. LiC104, KC104, NaC104, (C4Hg)4NBF4 or
(C2H5)4NBF4) at a working anode potential of 1.1 - 1.7 V.
This results in narwedine-type enones and their derivatives
The working electrode may be of platinum,graphite etc., the
working potential being determined by means of a reference
electrode. The medium may be acidic r neutral or alkaline
by the use of different additives such as Na2C03, K2C03,
NaHC03, HBF4, CH3COOH and the like.
The advantage of the method in acco~dance with
the present invention is the high purity state of the
final product. The unreacted starting material during
- 2 -
I

3~
the reaction is easily separated and recirculated to the
process.
The yield of the final product in accordance
with the electrochemical oxidation suggested can be 40%.
The unreacted starting material is introduced again in
the process, and thus a quantitative transformation of
the starting material in the final product is achieved.
By means of this electrochemical oxidation the yield is
higher than that of the other known methods of chemical
oxidation.
The invention is illustrated by the following
examples:
E~ample 1:
This example relates to the following
reaction 1 3 0
l ~ ~ N-CH
PhH2C0~ ~ ~ -CH --3 ~ Br ~ 3
3 Br 3
Ph = phenyl
0,001 moles of N-methyl-(4'-methoxyphenethyl)-2-
bromo-4-methoxy-5-benzyloxybenzamide in a methyl
cyanate solvent (benzamide to solvent ratio of 1:100),
containing 2.4% (C4Hg)4N~F4 (conductive salt) and 2% HBF
(acid) or KC104 and X2C03 was added into the anode compart-
ment of an electrolytic cell. The cathode compartment
and the electrolytic bridge of the reference electrode
contained the same solvent as used in the anodic com-
partment and the same percentage of conductive salt. The
working electxode was of platinum and the reference
3 -

electrode was Ag/Ag+ in methyl cyanate. The working anode
potential was 1.3 V. l'he oxidation was carried out at
a temperature below 0C for 3-5 hours, until the electric
charge,equivalent to the compound submitted to oxidation,
had flown. After the process was completed the solution
of the anode compartment was evaporated to dryness.
The residue thus obtained was dissolved in chloroform
and washed in bicarbonate solution and then water.
After the water was removed from the solution, the
solvent was evaporated. The residue was purified by
chromatography or by recrystallization. The yield of
the product 8-bromo-9-oxogalanthaminone as defined in
the above formula reached up to 40%.
Example 2
Similarly, the product 8 bromo-9-oxagalantha-
minone as defined in the formula below was obtained from
N methyl-~4'-benzyloxyphenethyl)-2-bromo-4,5-dimethoxy-
benzamide by oxidation with comparatively good yield.
The reaction is illustrated below:
0
oCH2Ph ll
2 5 H 3C O ~N -CH 3 ~- C1~ 3
CH30 Br CH30 Br
Ph = phenyl