Method of deuteration using mixed catalyst
View Patent ↗The subject of the present invention is to provide a method for deuteration, which can obtain a compound having an aromatic ring and/or a heterocyclic ring at an improved deuteration ratio. The present invention relates to a method for deuteration of a compound having an aromatic ring and/or a heterocyclic ring, comprising reacting the compound having an aromatic ring and/or a heterocyclic ring with a heavy hydrogen source in the presence of an activated mixed catalyst of not less than two kinds of catalysts selected from among a palladium catalyst, a platinum catalyst, a rhodium catalyst, an iridium catalyst, a ruthenium catalyst, a nickel catalyst and a cobalt catalyst.
1. A method for deuteration of a compound having a substituted benzene ring, comprising reacting the compound having the substituted benzene ring with a heavy hydrogen source in the presence of an activated mixed catalyst consisting of a palladium catalyst and a platinum catalyst under sealed reflux condition,
wherein the compound comprises at least one substituent bound to a benzene ring in the compound, and the substituent comprises at least one carbon atom and at least one hydrogen atom, the at least one hydrogen atom being bound to the at least one carbon atom in the substituent, and
wherein all hydrogen atoms that are bound to carbon atoms and are located in both the at least one substituent and the benzene ring of the compound are deuterated at a weight average deuteration ratio in a range of 74.5% or higher.
2. The method for deuteration according to claim 1 , wherein the heavy hydrogen source is a deuterated solvent.
3. The method for deuteration according to claim 2 , wherein the deuterated solvent is heavy water (D 2 O).
4. The method for deuteration according to claim 1 , wherein the activated mixed catalyst is a catalyst obtained by activating mixed non-activated catalysts consisting of a palladium catalyst and a platinum catalyst by contacting the non-activated catalysts with hydrogen gas or heavy hydrogen gas.
5. The method for deuteration according to claim 4 , wherein the contact of the non-activated mixed catalyst with the hydrogen gas or the heavy hydrogen gas is carried out in a reaction system of the deuteration.
6. The method for deuteration according to claim 1 , wherein the palladium catalyst is palladium carbon.
7. The method for deuteration according to claim 1 , wherein the platinum catalyst is platinum carbon.
8. The method for deuteration according to claim 1 , wherein the activated mixed catalyst of a palladium catalyst and a platinum catalyst has a weight ratio of each metal in the palladium catalyst and the platinum catalyst from 1:5 to 5:1.
9. The method for deuteration according to claim 1 , wherein the compound comprises at least one optionally substituted alkyl group as the at least one substituent.
10. The method for deuteration according to claim 1 , wherein the compound comprises at least one optionally substituted alkylamino group as the at least one substituent.
11. The method for deuteration according to claim 1 , wherein the at least one substituent in the compound is substituted with a carboxyl group.
12. The method for deuteration according to claim 1 , wherein the compound comprises at least one optionally substituted alkenyl group as the substituent.
13. The method for deuteration according to claim 1 , wherein at least one deuteration ratio of the hydrogen deuterated in the compound is higher than a deuteration ratio of the hydrogen obtained by a method using the palladium catalyst alone and a deuteration ratio of the hydrogen obtained by a method using the platinum catalyst alone.
14. The method for deuteration according to claim 1 , wherein the at least one substituent in the compound is at least one group selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylphosphino, arylphosphino, alkylphosphinoyl, arylphosphinoyl, alkylamino, arylamino, alkoxycarbonyl, aryloxycarbonyl, alkoxysulfonyl, aryloxysulfonyl, acyl, and acyloxy, which are optionally substituted.
15. The method for deuteration according to claim 1 , wherein the reacting the compound having the substituted benzene ring with the heavy hydrogen source in the presence of the activated mixed catalyst consisting of the palladium catalyst and the platinum catalyst is performed for a period from 1 to 50 hours.
16. A method for deuteration of a compound having a substituted benzene ring, comprising reacting the compound having the substituted benzene ring with a heavy hydrogen source in the presence of an activated mixed catalyst consisting of a palladium catalyst and a platinum catalyst under sealed reflux condition,
wherein the compound comprises at least one substituent bound to a benzoic ring in the compound, and the substituent comprises at least one carbon atom and at least one hydrogen atom, the at least one hydrogen atom being bound to the at least one carbon atom in the substituent, and
hydrogen bound to carbon in an ortho-position of the benzene ring relative to the substituent is deuterated more by the reacting step in the presence of an activated mixed catalyst than the hydrogen in the ortho-position deuterated in the presence of an activated palladium catalyst alone or in the presence of an activated platinum catalyst alone, wherein a weight average deuteration ratio of the hydrogen atoms that are bound to the carbon atoms and are located in both the at least one substituent and the benzene ring of the compound is 74.5% or higher.
17. The method for deuteration according to claim 16 , wherein the reacting step is performed for a period from 1 to 50 hours.