CA1187834A

CA1187834A - Method for the preparation of narwedine-type dienones and their derivatives

Info

Publication number: CA1187834A
Application number: CA000340093A
Authority: CA
Inventors: Radoslav Y. Vlahov; Maria S. Zagorova; Maya H. Hinova; Dikran A. Krikoryan; Stoyan P. Parushev
Original assignee: Edinen Centar Po Chimia
Current assignee: Edinen Centar Po Chimia
Priority date: 1978-11-21
Filing date: 1979-11-19
Publication date: 1985-05-28

Abstract

ABSTRACT OF THE DISCLOSURE:
The present invention relates to a method for the preparation of wherein A 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:

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 /\/ \

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 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:

oCH2Ph ll 2 5 H 3C O ~N -CH 3 ~- C1~ 3 CH30 Br CH30 Br Ph = phenyl

Claims

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:

wherein A 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:

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:

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:

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.