Method for preparing methylated amines

Patent metadata

Field	Value
Publication number	US-9783514-B2
Application number	US-201314404865-A
Country	US
Kind code	B2
Filing date	Jun 4, 2013
Priority date	Jun 5, 2012
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

The present invention relates to a method for preparing methylated amines using carbon dioxide and to the use of the method for manufacturing vitamins, pharmaceutical products, glues, acrylic fibres and synthetic leathers, pesticides and fertilisers. The invention also relates to a method for manufacturing vitamins, pharmaceutical products, glues, acrylic fibres, synthetic leathers, pesticides and fertilisers, including a step of preparing methylated amines by the method according to the invention. The present invention also relates to a method for preparing marked methylated amines and to the uses thereof.

First claim

The invention claimed is:

1. A process for the preparation of methylated amines of formula (I):

in which:
R 1 and R 2 represent, independently of one another,
a hydrogen atom, an alkyl group, an aryl group, or a heteroaryl group, said alkyl, aryl, and heteroaryl groups optionally being substituted, or
R 1 and R 2 , taken together with the nitrogen atom to which they are bonded, form an optionally substituted heterocycle,
R 1 and R 2 optionally comprise an H, C, N, O, F, Si and/or S as defined below;
H represents a hydrogen atom ( 1 H), deuterium ( 2 H) or tritium ( 3 H);
C represents a carbon atom ( 12 C) or a 11 C, 13 C or 14 C isotope;
N represents a nitrogen atom ( 14 N) or a 15 N isotope;
O represents an oxygen atom ( 16 O) or an 18 O isotope;
F represents a fluorine atom ( 19 F) or a 18 F isotope;
Si represents a silicon atom ( 28 Si) or a 29 Si or 30 Si isotope;
S represents a sulfur atom ( 32 S), or a 33 S, 34 S or 36 S isotope;
comprising a step of reacting an amine of formula (II), in which R 1 and R 2 and N are as defined above:

with CO 2 , in which C and O are as defined above, in the presence of a catalyst and of a silane compound of formula (III):

in which:
H is as defined above,
R 3 , R 4 and R 5 represent, independently of one another,
a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, a silyl group or a siloxy group, said alkyl, alkoxy, silyl, siloxy, and aryl groups optionally being substituted.

2. The process as claimed in claim 1 , wherein the catalyst is selected from the group consisting of organic catalysts and metal catalysts, the metal catalysts being chosen from metal salts or metal complexes.

3. The process as claimed in claim 2 , wherein the organic catalyst is:
a secondary or tertiary amine selected from the group consisting of triazabicyclodecene (TBD), N-methyltriazabicyclodecene (MeTBD), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), trimethylamine, triethylamine, piperidine, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]octane (DABCO), proline, phenylalanine, a thiazolium salt and N-diisopropylethylamine (DIPEA or DIEA), or
an N-heterocyclic carbene resulting from an imidazolium salt selected from the group consisting of 1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-3-ium (carbene A), 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazol-3-ium (carbene C), 1,3-bis(2,4,6-trimethylphenyl)-1H-imidazol-3-ium (carbene B), 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro-1H-imidazol-3-ium (carbene D), 4,5-dichloro-1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-3-ium (carbene E), 1,3-di(tert-butyl)-1H-imidazol-3-ium (carbene F) and 1,3-di(tert-butyl)-4,5-dihydro-1H-imidazol-3-ium salts, said salts being in the form of chloride salts.

4. The process as claimed in claim 2 , wherein the metal catalyst is selected from the group consisting of metal salts or complexes of:
metals chosen from boron, silicon, aluminum, gallium, tin or indium;
alkali metals chosen from sodium or potassium;
alkaline earth metals chosen from magnesium or calcium;
transition metals selected from the group consisting of nickel, iron, cobalt, zinc, copper, rhodium, ruthenium, platinum, palladium and iridium; and
rare earth metals chosen from lanthanum, cerium, praseodymium or neodymium.

5. The process as claimed in claim 1 , wherein the reaction is carried out under a CO 2 pressure of between 1 and 50 bar, limits included.

6. The process as claimed in claim 1 , wherein the reaction is carried out at a temperature of between 25 and 150° C., limits included.

7. The process as claimed in claim 1 , wherein the reaction is carried out for a period of time of 5 minutes to 72 hours, limits included.

8. The process as claimed in claim 1 , wherein the reaction is carried out in a mixture of at least two solvent(s) selected from the group consisting of:
ethers,
hydrocarbons,
nitrogenous solvents,
sulfoxides, and
alkyl halides.

9. The process as claimed in claim 1 , wherein the solvent is the amine of formula (II).

10. The process as claimed in claim 1 , wherein the molar ratio of the silane compound of formula (III) to the amine of formula (II) is from 1 to 10, limits included.

11. The process as claimed in claim 1 , wherein the amount of catalyst is from 0.001 to 1 molar equivalent, limits included, with respect to the amine of formula (II).

12. A process for the manufacture of vitamins, pharmaceutical products, adhesives, acrylic fibers, synthetic leather, pesticides and fertilizers comprising a step of preparing methylated amines of formula (I) by reacting an amine of formula (II) with CO 2 in the presence of a catalyst and of a silane compound of formula (III) as claimed in claim 1 .

13. A process for the manufacture of tracers and radioactive tracers, wherein the process comprises a step of preparation of labeled methylated amines of formula (I) as claimed in claim 1 .

14. The process as claimed in claim 1 , wherein the reaction is carried out under a CO 2 pressure of between 1 and 30 bar, limits included.

15. The process as claimed in claim 1 , wherein the reaction is carried out under a CO 2 pressure of between 1 and 10 bar, limits included.

16. The process as claimed in claim 1 , wherein the reaction is carried out at a temperature of between 50 and 125° C., limits included.

17. The process as claimed in claim 1 , wherein the reaction is carried out for a period of time of 15 minutes to 48 hours.

18. The process as claimed in claim 1 , wherein the reaction is carried out in a mixture of at least two solvent(s) selected from the group consisting of diethyl ether, THF, benzene, toluene, pyridine, acetonitrile, dimethyl sulfoxide, chloroform, and methylene chloride.

Assignees

• Commissariat Energie Atomique

Inventors

• Cantat Thibault
• Gomes Christophe
• Jacquet Olivier

Classifications

• C07D295/00 Primary

  Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms · CPC title

• C07B59/002

  Heterocyclic compounds · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07C217/82

  of the same non-condensed six-membered aromatic ring · CPC title

• C07C211/08

  containing alkyl groups having a different number of carbon atoms · CPC title