
Dihydromorphinones from morphine and analogs
============================================

German Patents 607931, 617238 (both from 1935) and 623821 (1936), all 
describing the rearrangement of morphine, codeine and ethylmorphine into 
the corresponding dihydromorphinones. The first uses immense amounts of 
platinum or palladium in acid solution to affect the rearrangement, the 
second uses a lot less catalyst, and the last one uses alcohol as solvent, 
in which the reaction proceeds without any acid added. 

Translated from german by Rhodium. Thanks to Piglet for sending me copies 
of the original patents. 


Deutsches Reichspatent 607,931
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Procedure for the Production of Dihydromorphinones
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	It is well known that morphine and its ethers, through treatment 
with hydrogen gas in the presence of large amounts of noble metal catalysts 
through heating the acid soln., can be transformed to the dihydrated keto 
derivatives. 
	Surprisingly, it was now found that for this transformation to take 
place, hydrogen is completely unnecessary, and that just heating the 
acidified alkaloid solution with a larger amount of finely divided platinum 
row metals, will suffice to affect the simultaneous dehydration/hydration 
in good yields. 
	This success is particularly unexpected because it was not to be 
foreseen that platinum metal not saturated with hydrogen is capable to use 
the hydrogen originating from the dehydrogenation [of the 6-position] 
almost quantitatively for the hydrogenation of the double bond [in the 7-8 
position] of morphine or its analogs without in addition of excess 
hydrogen from an external source. 

Example 1:

300 grams of codeine free base was dissolved in 2000ml dilute HCl, and 
after the addition of 150 grams finely divided palladium, the mixture was 
heated under reflux for one hour. After the palladium was filtered off, the 
acid filtrate was basified with NaOH solution. The base which separated was 
recrystallized from alcohol. Yield of dihydrocodeinone 75-85%, mp 195°C.

Example 2:

5 grams of codeine hydrochloride was dissolved in 30 ml water, and 
acidified with a little HCl, and after the addition of 4 grams platina 
black, the solution was refluxed for 5 hours. After workup as in example 1, 
the yield was 65-75% of theory. 

Example 3:

5 g of morphine HCl was dissolved in 50ml water, slightly acidified with 
HCl, and 5 grams of platina black was added and the solution refluxed for 
4 hours. Workup as in example 1. Yield 2.5 grams dihydromorpinone.

Example 4:

To a solution of codeine hydrochloride, slightly acidified with HCl, 50 ml 
of a 10% solution of colloidal platinum was added, and the solution was
refluxed for 3 hours. Workup as in example 1. Yield 3 g dihydrocodeinone. 

Example 5:

6 grams codeine freebase was dissolved in a solution of 4 grams of tartaric 
acid in 50 ml of water, and 6 grams palladium black was added. The solution 
was refluxed for 1 hour and worked up as in example 1. Yield 75% of theory. 

Example 6:

6 g codeine phosphate was dissolved in 30 ml water, and acidified with 5ml
dilute phosphoric acid. 4g of finely divided palladium was added, and the 
solution was refluxed for one hour. Workup as in example 1. Yield 60-70%.

Example 7:

6 grams of codeine free base was dissolved in dilute acetic acid, and was 
refluxed for two hours after the addition of 5 grams palladium black. 
After workup as in example 1, the yield was 40% of theory. 
 
Example 8:

21 grams of codeine free base was dissolved in an excess of dilute sulfuric 
acid, mixed with 16 grams palladium black and refluxed for one hour. After
workup as in example 1, the yield was 80-85% of theory. 

Example 9:

10 grams of ethylmorphine was mixed with 50 ml water and acidified with 
HCl. 10 grams of platina black was added and the mixture was refluxed. 
The yield of ethyldihydromorphinone was 65-75% of theory. 


Deutsches Reichspatent 617,238
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Procedure for the Production of Dihydromorphinones
==================================================

	As in patent 607931, a method is decribed below for the production 
of dihydromorphinones by rearrangement without the use of hydrogen, but 
simply by heating the alkaloid in an acidic solution together with a 
platinum catalyst.
	While in patent 607931, realtively large amounts of platinum 
catalyst is used, we have found that only a fraction of that amount is 
needed, and sometimes with even better yields. 

Example 1:

300g codeine freebase was dissolved in 2000ml dilute HCl, and was heated 
with 25g of finely powdered palladium, and boiled under reflux for an hour. 
The palladium was filtered off, and the filtrate basified with NaOH 
solution. The precipitated base was recrystallized from alcohol. Yield 
85-95% of dihydrocodeinone, mp 195°C. 

Example 2:

5 grams of codeine hydrochloride was dissolved in 30ml water, and acifified 
with a small amount of HCl, and after the addition of 0.5g of palladium
black, the mixture was refluxed for five hours, and worked up as in example 
1. The yield was 70% of theoretical.

Example 3:

5 grams of morphine hydrochloride was dissolved in a slightly acid HCl 
solution, and after the addition of 0.5g palladium black, the mixture was
refluxed for three hours and worked up as in example 1. The yield was 3g. 

Example 4:

6 grams of codeine freebase was dissolved in 30ml water together with 4g of
tartaric acid, and 0.5g of palladium black was added. The mixture was
refluxed for one hour and worked up as in example 1. The yield was 75% of
theory. 
 
Example 5:

6 grams of codeine phosphate was dissolved in 30ml water, and acidified 
with 5ml dilute phosphoric acid, and after the addition of 0.5g of 
palladium black, the solution was refluxed for an hour. After workup as in 
example 1, 60-70% yield of dihydrocodeinone was isolated. 

Example 6:

21 grams of codeine freebase was dissolved in an excess of dilute H2SO4, 
and two grams of palladium black was added and the solution refluxed for 
one hour. The yield was 90% of theory.

Example 7:

10 grams of ethylmorphine freebase was added to 50ml water, and HCl was 
added until the solution was slightly acidic and all ethylmorphine had 
dissolved. 1 gram palladium black was added, and the solution was boiled 
under reflux. The mixture was worked up as in example 1. The yield of 
ethyldihydromorphinone was 75% of theory. 



Deutsches Reichspatent 623,821
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Procedure for the Production of Dihydromorphinones
==================================================

	As in patent 617238, a method is decribed below for the production 
of dihydromorphinones without the addition of hydrogen gas. 
	While the rearrangement in patent 617238 is affected by the 
presence of acids, we have now found that the reaction with morphine and 
its ethers is taking place in an alcoholic solution in good yields without 
the addition of any acid. 

Example 1:

5 grams morphine was dissolved in 50 ml of alcohol and after the addition 
of 0.5g of palladium black, the mixture was refluxed for 4 hours. After the 
catalyst wass filtered off and the solution concentrated, dihydromorphinone 
crystallized. Yield 3 grams. 

Example 2:

10 grams of codeine was dissolved in 100ml alcohol, and after the addition 
of 0.5 grams palladium black the solution was refluxed for 4 hours. Workup 
as in example 1. Yield 7 grams of dihydrocodeinone.

Example 3:

5 g ethylmorphine and 0.3g of palladium black was dissolved in alcohol and
the solution was refluxed. Yield 3g of ethyldihydromorphinone.

