Method for preparing alkylamines

Abstract

The present invention relates to a method for preparing alkylamines using carbon monoxide and the use of this method in the manufacturing of vitamins, pharmaceutical products, adhesives, acrylic fibres and synthetic leathers, pesticides, surfactants, detergents and fertilisers. It also relates to a method for manufacturing vitamins, pharmaceutical products, adhesives, acrylic fibres, synthetic leathers, pesticides, surfactants, detergents and fertilisers, comprising a step of preparing alkylamines by the method according to the invention. The present invention further relates to a method for preparing marked alkylamines and uses thereof.

Claims

1. A method for preparing alkylamines of formula (I): ##STR00055## wherein: R.sup.1, R.sup.2 and R.sup.3 represent, independently of each other, a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle groups being optionally substituted; or R.sup.1 and R.sup.2, taken together with the nitrogen atom to which they are bound, form a heterocycle, optionally substituted, and R.sup.3 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle groups being optionally substituted; m, m′, m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; R.sup.1, R.sup.2 and R.sup.3 and —CH.sub.2— optionally comprise H, C, N, O, F and/or S as defined below: H represents a hydrogen atom (.sup.1H), deuterium (.sup.2H) or tritium (.sup.3H); C represents a carbon atom (.sup.12C), an isotope .sup.11C, .sup.13C or .sup.14C; N represents a nitrogen atom (.sup.14N); an isotope .sup.15N; O represents a oxygen atom (.sup.16O); an isotope .sup.17O or .sup.18O; F represents a fluorine atom (.sup.19F), an isotope .sup.18F; S represents a sulphur atom (.sup.32S), an isotope .sup.33S, .sup.34S or .sup.36S; characterised by reacting an amine of formula (II) ##STR00056## wherein R.sup.1, R.sup.2 and R.sup.3, —CH.sub.2—, m, m′ and m″ are as defined above; R represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle groups being optionally substituted; X represents a halogen atom, trifluoromethylsulfonate (triflate), methanesulfonate (mesylate), p-toluenesulfonic acid (tosylate); n is an integer chosen from 0 and 1; with CO wherein C and O are as defined above and a reducing agent chosen from H.sub.2, LiAlH.sub.4, NaBH.sub.4, Zn, LiBH.sub.4, a silane of formula (III) ##STR00057##  and a borane of formula (IV) ##STR00058## wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 represent, independently of each other, a hydrogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, a silyl group, a siloxy group, an amino group, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, silyl, siloxy and amino groups being optionally substituted; or R.sup.7 and R.sup.8 taken together with the boron atom to which they are bound form a heterocycle, optionally substituted; in the presence of a metal catalyst, and optionally a promoter; wherein the catalyst is a metal salt wherein the metal is a transition metal chosen from chromium, tungsten, manganese, rhenium, silver, ruthenium, rhodium, cobalt, iron, nickel, copper, iridium, osmium, molybdenum, gold, platinum and palladium, and the anions forming the salts with the aforementioned transition metals are chloride (Cl.sup.−), sulphate (SO.sub.4.sup.2−), sulphide (S.sup.2−), nitrate (NO.sub.3.sup.−), oxide (O.sup.2−) and hydroxide (OH.sup.−); with the substitution on alkyl, alkenyl and alkynyl groups being one or more hydroxyl groups, one or more alkoxy groups, one or more aryl groups, one or more halogen atoms chosen from fluorine, chlorine, bromine and iodine atoms, one or more nitro groups (—NO.sub.2), one or more nitrile groups (—CN), one or more alkyl groups, the substitution on heteroaryl and heterocycle groups being one or more hydroxyl groups, one or more alkoxy groups, one or more aryl groups, one or more halogen atoms chosen from fluorine, chlorine, bromine and iodine atoms, one or more nitro groups (—NO.sub.2), one or more nitrile groups (—CN), one or more alkyl groups, and the substitution on aryl groups being one or more hydroxyl groups, one or more alkoxy groups, one or more siloxy groups, one or more halogen atoms chosen from fluorine, chlorine, bromine and iodine atoms, one or more nitro groups (—NO.sub.2), one or more nitrile groups (—CN), one or more alkyl groups.

2. A method for preparing alkylamines of formula (I): ##STR00059## wherein: R.sup.1, R.sup.2 and R.sup.3 represent, independently of each other, a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle groups being optionally substituted; or R.sup.1 and R.sup.2, taken together with the nitrogen atom to which they are bound, form a heterocycle, optionally substituted, and R.sup.3 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle groups being optionally substituted; m, m′, m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; R.sup.1, R.sup.2 and R.sup.3 and —CH.sub.2— optionally comprise H, C, N, O, F and/or S as defined below: H represents a hydrogen atom (.sup.1H), deuterium (.sup.2H) or tritium (.sup.3H); C represents a carbon atom (.sup.12C) an isotope .sup.11C, .sup.13C or .sup.14C; N represents a nitrogen atom (.sup.14N), an isotope .sup.15N; O represents an oxygen atom (.sup.16O), an isotope .sup.17O or .sup.18O; F represents a fluorine atom (.sup.19F), an isotope .sup.18F; S represents a sulphur atom (.sup.32S), an isotope .sup.33S, .sup.34S or .sup.36S; characterised by reacting an amine of formula (II) ##STR00060## wherein R.sup.1, R.sup.2 and R.sup.3, —CH.sub.2—, m, m′ and m″ are as defined above; R represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle groups being optionally substituted; X represents a halogen atom, trifluoromethylsulfonate (triflate), methanesulfonate (mesylate), p-toluenesulfonic acid (tosylate); n is an integer chosen from 0 and 1; with CO wherein C and O are as defined above and a reducing agent chosen from Hz, LiAlH.sub.4, NaBH.sub.4, Zn, LiBH.sub.4, a silane of formula (III) ##STR00061##  and a borane of formula (IV) ##STR00062## wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 represent, independently of each other, a hydrogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, a silyl group, a siloxy group, an amino group, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, silyl, siloxy and amino groups being optionally substituted; or R.sup.7 and R.sup.8 taken together with the boron atom to which they are bound form a heterocycle, optionally substituted; in the presence of a metal catalyst, and optionally a promoter; wherein the catalyst is a metal complex wherein the metal is a transition metal chosen from chromium, tungsten, manganese, rhenium, silver, ruthenium, rhodium, cobalt, iron, nickel, copper, iridium, osmium, molybdenum, gold, platinum and palladium, and the ligands being bound to the transition metals are chosen from: nitrogenous bases chosen from trimethylamine, triethylamine, piperidine, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]octane (DABCO), proline, phenylalanine, a thiazolium salt, N-diisopropylethylamine (DIPEA or DIEA), bipyridyl (bipy), terpyridine (terpy); phenanthroline (phen), ethylenediamine, N,N,N′,N′-tetra-methyl-ethylenediamine (TMEDA), quinoline and pyridine; phosphorous bases chosen from triphenylphosphine, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), triisopropylphosphine, tris[2-diphenylephosphino)ethyl]phosphine (PP.sub.3), tricyclohexylphosphine, 1,2-bis-diphenylphosphinoethane (dppe), 1,2-bis(diphenylphosphino)ethane (dppb); alkyl and aryl phosphonates chosen from diphenylphosphate, triphenylphosphate (TPP), tri(isopropylphenyl)phosphate (TIPP), cresyldiphenyl phosphate (CDP), tricresylphosphate (TCP); alkyl and aryl phosphates chosen from di-n-butylphosphate (DBP), tris-(2-ethylhexyl)-phosphate and triethyl phosphate; oxygenated bases chosen from acetate (OAc), acetylacetonate, methanolate, ethanolate, benzoyl peroxide; silylated ligands chosen from triphenylsilyl, diphenylhydrosilyl, trimethylsilyl, dimethylhydrosilyl, triethylsilyl, triethoxysilyl; carbonaceous ligands chosen from CO, CN.sup.−, and N-heterocyclic carbenes from an imidazolium salt chosen from the salts of 1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-3-ium, 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazol-3-ium, 1,3-bis(2,4,6-trimethylphenyl)-1H-imidazol-3-ium, 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro-1H-imidazol-3-ium, 4,5-dichloro-1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-3-ium, 1,3-di-tert-butyl-1H-imidazol-3-ium, 1,3-di-tert-butyl-4,5-dihydro-1H-imidazol-3-ium, said salts being in the form of chloride salts; the metal complex optionally comprising a counterion chosen from sodium (Na.sup.+), potassium (K.sup.+), ammonium (NH.sub.4.sup.+); with the substitution on alkyl, alkenyl and alkynyl groups being one or more hydroxyl groups, one or more alkoxy groups, one or more aryl groups, one or more halogen atoms chosen from fluorine, chlorine, bromine and iodine atoms, one or more nitro groups (—NO.sub.2), one or more nitrile groups (—CN), one or more alkyl groups, the substitution on heteroaryl and heterocycle groups being one or more hydroxyl groups, one or more alkoxy groups, one or more aryl groups, one or more halogen atoms chosen from fluorine, chlorine, bromine and iodine atoms, one or more nitro groups (—NO.sub.2), one or more nitrile groups (—CN), one or more alkyl groups, and the substitution on aryl groups being one or more hydroxyl groups, one or more alkoxy groups, one or more siloxy groups, one or more halogen atoms chosen from fluorine, chlorine, bromine and iodine atoms, one or more nitro groups (—NO.sub.2), one or more nitrile groups (—CN), one or more alkyl groups.

3. The method according to claim 1, wherein R.sup.1, R.sup.2 and R.sup.3 represent, independently of each other, a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 1; m, m′ and m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; n=0.

4. The method according to claim 1, wherein R.sup.1 and R.sup.2, taken together with the nitrogen atom to which they are bound, form a heterocycle, optionally substituted as defined in claim 1, and R.sup.3 represents a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups optionally being substituted as defined in claim 1; m, m′ and m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; n=0.

5. The method according to claim 1, wherein R.sup.1, R.sup.2 and R.sup.3 represent, independently of each other, a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 1; R represents a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 1; m, m′ and m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; n=1; X represents a halogen atom, trifluoromethylsulfonate (triflate), methanesulfonate (mesylate), p-toluenesulfonic acid (tosylate).

6. The method according to claim 1, wherein R.sup.1 and R.sup.2, taken together with the nitrogen atom to which they are bound, form a heterocycle, optionally substituted as defined in claim 1, and R.sup.3 represents a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 1; R represents a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 1; m, m′ and m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; n=1; X represents a halogen atom, trifluoromethylsulfonate (triflate), methanesulfonate (mesylate), p-toluenesulfonic acid (tosylate).

7. The method according to claim 1, wherein the values of m, m′, m″, q, q′ and q″ in the alkylamines of formula (I) are chosen so that: 0≤m+q≤10; and/or 0≤m′+q′≤10; and/or 0≤m″+q″≤10.

8. The method according to claim 1, wherein the reducing agent is chosen from Hz, a silane of formula (III) ##STR00063## and a borane of formula (IV) ##STR00064## wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 represent, independently of each other, a hydrogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, a silyl group, a siloxy group, an amino group, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, silyl, siloxy and amino groups being optionally substituted as defined in claim 1; or R.sup.7 and R.sup.8, taken together with the boron atom to which they are bound, form an optionally substituted heterocycle, the substitution being as defined in claim 1.

9. The method according to claim 1, wherein the promoter is of formula RX, with R representing a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 1; and X representing a halogen atom, trifluoromethylsulfonate (triflate), methanesulfonate (mesylate), p-toluenesulfonic acid (tosylate).

10. The method according to claim 2, wherein R.sup.1, R.sup.2 and R.sup.3 represent, independently of each other, a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 2; m, m′ and m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; n=0.

11. The method according to claim 1, wherein R.sup.1 and R.sup.2, taken together with the nitrogen atom to which they are bound, form a heterocycle, optionally substituted as defined in claim 1, and R.sup.3 represents a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups optionally being substituted as defined in claim 1; m, m′ and m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; n=0.

12. The method according to claim 2, wherein R.sup.1, R.sup.2 and R.sup.3 represent, independently of each other, a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 2; R represents a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 2; m, m′ and m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; n=1; X represents a halogen atom, trifluoromethylsulfonate (triflate), methanesulfonate (mesylate), p-toluenesulfonic acid (tosylate).

13. The method according to claim 2, wherein R.sup.1 and R.sup.2, taken together with the nitrogen atom to which they are bound, form a heterocycle, optionally substituted as defined in claim 2, and R.sup.3 represents a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 2; R represents a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 2; m, m′ and m″ are integers chosen from 0 and 1; q, q′, q″ are integers chosen from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; n=1; X represents a halogen atom, trifluoromethylsulfonate (triflate), methanesulfonate (mesylate), p-toluenesulfonic acid (tosylate).

14. The method according to claim 2, wherein the values of m, m′, m″, q, q′ and q″ in the alkylamines of formula (I) are chosen so that: 0≤m+q≤10; and/or 0≤m′+q′≤10; and/or 0≤m″+q″≤10.

15. The method according to claim 2, wherein the reducing agent is chosen from H.sub.2, a silane of formula (III) ##STR00065## and a borane of formula (IV) ##STR00066## wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 represent, independently of each other, a hydrogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, a silyl group, a siloxy group, an amino group, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, silyl, siloxy and amino groups being optionally substituted as defined in claim 2; or R.sup.7 and R.sup.8, taken together with the boron atom to which they are bound, form an optionally substituted heterocycle, the substitution being as defined in claim 2.

16. The method according to claim 2, wherein the promoter is of formula RX, with R representing a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle, said alkyl, aryl, heteroaryl, heterocycle groups being optionally substituted as defined in claim 2; and X representing a halogen atom, trifluoromethylsulfonate (triflate), methanesulfonate (mesylate), p-toluenesulfonic acid (tosylate).

17. The method according to claim 1, wherein the method further takes place in the presence of an additive chosen from aromatic amides chosen from acetanilide, benzanilide and N-methylacetanilide; Lewis acids chosen from AlCl.sub.3, LiCl, LiBF.sub.4, FeCl.sub.3, InCl.sub.3, BiCl.sub.3.

18. The method according to claim 2, wherein the method further takes place in the presence of an additive chosen from aromatic amides chosen from acetanilide, benzanilide and N-methylacetanilide; Lewis acids chosen from AlCl.sub.3, LiCl, LiBF.sub.4, FeCl.sub.3, InCl.sub.3, BiCl.sub.3.

Description

(1) Other advantages and features of the present invention will become apparent upon reading the following examples given by way of illustration and as limitations, and with reference to the accompanying figures.

(2) FIG. 1 shows the alkylation of amines using alcohols or haloalkanes via the Fischer-Tropsch method.

(3) FIG. 2 shows the reduction of amides into amines by hydrosilylation of the amides in the presence of Co.sub.2CO.sub.8 as a catalyst.

(4) FIG. 3 shows the undesirable reactions likely to occur when the carbonylation reaction is conducted in the presence of a reducing agent and a promoter and when the reduction is conducted in the presence of CO. For example, the silanes (reducing agent) are known to form methane in the presence of iodomethane (promoter), which would deactivate the system, or to form a silylated amine in the presence of an amine.

EXAMPLES

(5) In all the examples, the reagents used, in particular the amine of formula (II), the catalyst, the promoter and the reducing agent are commercially available products or can be synthesised by following the procedures described in the literature. In particular the synthesis of NaCoCO.sub.4 is described in F. W. Edgell, J. Lyford, Inorg. Chem., 1970, 1932, and the synthesis of N-methyl-1,2,3,4-tetrahydroisoquinoline in C. Casagrande, A. Galli, R. Ferrini, G. Miragoli, Farmaco, Edizione Scientifica, 1972, 445. The remainder of the products used are purchased from Sigma-Aldrich.

Example 1: Preparation of Alkylamines of Formula (I) with Variable Chain Lengths

(6) The method for preparing alkylamines of formula (I) can be implemented in a single step and in a single reaction mixture and in the same autoclave (one step one-pot) according to the following experimental protocol.

(7) An autoclave is loaded in a glovebox with the catalyst (between 0.001 and 0.1 molar equivalent), the amine of formula (II) (1 molar equivalent), the promoter (between 0.1 and 1 molar equivalent), the reducing agent (between 1 and 6 molar equivalents), optionally an additive and the solvent. The concentration of amine of formula (II) in the reaction medium is between 0.05 M and 0.3 M. The introduction order is not of importance.

(8) The autoclave is sealed and then purged several times (4 times) with 10 bar of CO and then the temperature is raised to between 50 and 200° C. in 35 minutes. The CO pressure is maintained between 1 and 100 bar. The reaction time is from 1 to 24 hours.

(9) Once the reaction has ended, the autoclave is cooled to ambient temperature (20±5° C.). The crude reaction mixture is filtered on Celite. The volatile compounds are eliminated under reduced pressure and the reaction mixture containing the various alkylamines is purified by silica gel chromatography using a mixture of ethyl acetate and n-pentane as eluent for obtaining analytically pure alkylamines.

(10) A set of results is presented below in Table 1, giving examples of conversions of amines of formula (II) into alkylamines (determined by NMR) using phenylsilane PhSiH.sub.3 (sold by Aldrich) as a reducing agent, optionally CH.sub.3I (sold by Aldrich) as a promoter, and Co.sub.2CO.sub.8 and FeCO.sub.5 (sold by Aldrich) as catalysts, in accordance with the conditions presented below.

(11) TABLE-US-00001 TABLE 1 Reducing Amine agent Catalyst Conditions Conversion Products 0 PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 60 bar, 7 h, 200° C. Promoter: CH.sub.3I (0.33 eq.) Solvent: MeCN (0.3M) 88% PhSiH.sub.3 (2 eq.) FeCO.sub.5 (0.06 eq.) CO 60 bar, 7 h, 200° C. Promoter: CH.sub.3I (0.33 eq.) Solvent: MeCN (0.3M) 65% PhSiH.sub.3 (1.5 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 50 bar, 10 h, 200° C. Solvent: MeCN (0.2M) 93% PhSiH.sub.3 (1.5 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 50 bar, 7 h, 180° C. Solvent: MeCN (0.2M) 78%

(12) The yields are determined by GC/MS. The alkylamine yields have not been optimised but are encouraging. The by-products obtained are the corresponding amides. They can be recycled and can serve as starting products.

(13) The results show that the operating conditions specified above lead to mixtures of alkylamines wherein the length of each alkyl chain may be different and vary independently. The reaction conditions are therefore very important for the selectivity and efficacy of the reaction.

Example 2: Preparation of Alkylamines of Formula (I) with Variable Chain Lengths

(14) The same operating method as the one in example 1 is followed. In this example, various reducing agents were tested.

(15) The results are presented below in Table 2.

(16) TABLE-US-00002 TABLE 2 Reducing Amine agent Catalyst Conditions Conversion Products PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 50 bar, 7 h, 200° C., Solvent: MeCN (0.2M) 99% 0 PhSiH.sub.3 (3 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 50 bar, 7 h, 200° C. Solvent: MeCN (0.2M) 90% Ph.sub.2SiH.sub.2 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 50 bar, 7 h, 200° C. Solvent: MeCN (0.2M) 99% H.sub.2 (50 bar) Co.sub.2CO.sub.8 (0.06 eq.) CO 50 bar, 15 h, 200° C. Solvent: MeCN (0.2M) 40% Et.sub.3SiH (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 50 bar, 15 h, 200° C. Solvent: MeCN (0.2M) 94%

(17) The amount of reducing agent and the type of reducing agent are crucial factors since the yield depends on this significantly. The yields are determined by GC/MS. The alkylamine yields were not optimised but are encouraging. The by-products obtained are the corresponding amides that come from the carbonylation of the corresponding alkylamines. These amides can be recycled and can serve as starting products.

Example 3: Preparation of Alkylamines of Formula (I) with Controlled Chain Lengths

(18) A) Control by Reaction in Two Steps in the Same Autoclave (Two Steps One-Pot)

(19) The method for preparing alkylamines of formula (I) can be implemented in two steps and in a single reaction mixture (two steps one-pot) according to the following experimental protocol.

(20) An autoclave is loaded in a glovebox with the catalyst (between 0.001 and 0.1 molar equivalent), the amine of formula (II) (1 equivalent), the promoter (between 0.3 and 1 molar equivalent) and the solvent. The concentration of amine of formula (II) in the reaction medium is between 0.01 M and 0.3 M. The introduction order is of no importance.

(21) The autoclave is sealed and then purged several times (4 times) with 10 bar of CO and then the temperature is raised to between 150 and 200° C. in 35 minutes. The CO pressure is maintained between 1 and 100 bar. The reaction time is 1 to 24 hours.

(22) The autoclave is next purged 4 times with 5 bar of argon and then the reducing agent (between 1 and 6 molar equivalents) is introduced. The autoclave is next heated to between 50 and 200° C. for 1 to 10 hours.

(23) Once the reaction has ended, the autoclave is cooled to ambient temperature (20±5° C.). The crude reaction mixture is filtered on Celite. The volatile compounds are eliminated under reduced pressure and the reaction mixture containing the various alkylamines is purified by silica gel chromatography using a mixture of ethyl acetate/n-pentane as eluent to obtain analytically pure alkylamines.

(24) The reaction scheme is as follows:

(25) ##STR00028##

(26) TABLE-US-00003 TABLE 3 Reducing Amine agent Catalyst Conditions Conversion Products PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) 1) CO 60 bar, catalyst, promoter (CH.sub.3I 0.8 eq.), 200° C., 10 h 2) Ar 1 bar, reducing agent, 200° C., 6 h 70% 0

(27) This result shows that the operating conditions specified above lead to an alkylamine whose alkyl chain is lengthen in a controlled manner. All the converted amine gives the corresponding alkylamine. The reaction is therefore particularly clean since no by-product is obtained. In addition, the amine that has not reacted can be recycled.

(28) B) Control by Pressure

(29) A Wilmad NMR tube (or an autoclave) is loaded in a glovebox with the catalyst (between 0.001 and 0.1 molar equivalent), the amine of formula (II) (1 equivalent), the promoter (between 0.3 and 1 molar equivalent) and the solvent. The concentration of amine is between 0.01 M and 0.3 M. The introduction order is of no importance.

(30) An additive (between 0.05 and 1 molar equivalent) may be added in order to promote the reaction. This additive may be an amide or a Lewis acid as described previously.

(31) The tube is sealed and then purged a plurality of times (twice) with 10 bar of CO. The tube is next pressurised at a CO pressure of between 1 and 30 bar. The tube is next heated to between 50° C. and 150° C.

(32) Once the reaction has ended, the autoclave is cooled to ambient temperature (20±5° C.). The crude reaction mixture is filtered on Celite. The volatile compounds are eliminated under reduced pressure and the reaction mixture containing the alkylamines is purified by silica gel chromatography using a mixture of ethyl acetate and n-pentane as eluent in order to obtain the analytically pure alkylamines.

(33) A set of results is presented below in Table 4, giving examples of conversions of amines of formula (II) into alkylamines (determined by NMR) using phenylsilane PhSiH.sub.3 (sold by Aldrich) as a reducing agent, optionally CH.sub.3I and CH.sub.3CH.sub.2I (sold by Aldrich), as a promoter, N-ethylacetanilide and AlCl.sub.3 as additives (sold by Aldrich), and CO.sub.2CO.sub.8, and CO.sub.2CO.sub.8+bpy and FeCO.sub.5 (sold by Aldrich), and NaCoCO.sub.4 manufactured according to the method described in the reference mentioned above, as catalysts, according to the conditions presented below.

(34) TABLE-US-00004 TABLE 4 Reducing Amine agent Catalyst Conditions Conversion Products PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 + bpy (0.06 eq.) CO 8 bar, 17 h, 200° C. Promoter: CH.sub.3I (0.3 eq.) Solvent: MeCN (0.3M) 20% PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 + bpy (0.06 eq.) CO 8 bar, 17 h, 200° C. Promoter: CH.sub.3I (0.3 eq.) Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: MeCN (0.3M) 50% PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 17 h, 200° C. Promoter: CH.sub.3I (0.3 eq.) Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: MeCN (0.3M) 46% PhSiH.sub.3 (2 eq.) NaCoCO.sub.4 (0.06 eq.) CO 8 bar, 17 h, 200° C. Promoter: CH.sub.3I (0.3 eq.) Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: MeCN (0.3M) 46% PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 17 h, 200° C. Promoter: CH.sub.3I (0.3 eq.) Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: toluene (0.3M) 25% 0 PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 17 h, 200° C. Promoter: CH.sub.3CH.sub.2I (0.3 eq.) Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: MeCN (0.3M) 17% PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 17 h, 200° C. Promoter: CH.sub.3I (0.3 eq.) Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: toluene (0.3M) 50% PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 17 h, 200° C. Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: MeCN (0.3M) 45% PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 17 h, 150° C. Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: MeCN (0.3M) 53% PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 17 h, 100° C. Additive: N-ethyl- acetanilide (0.3 eq.) Solvent: MeCN (0.3M) 46% 0 PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 17 h, 100° C. Additive: AlCl.sub.3 (0.3 eq.) Solvent: MeCN (0.3M) 17% PhSiH.sub.3 (2 eq.) Co.sub.2CO.sub.8 (0.06 eq.) CO 8 bar, 16 h, 200° C. Promoter: CH.sub.3I (0.3 eq.) Additive: N- ethylacetanilide (0.3 eq.) Solvent: toluene (0.3M) 40%

(35) The yields are determined by GC/MS. The alkylamine yields were not optimised but are encouraging. The possible by-products obtained are the corresponding amides that result from the carbonylation of the corresponding alkylamines. These amides can be recycled and can serve as starting products.

(36) The results show that, under the operating conditions indicated in Table 4, the conversion of amines of formula (II) into alkylamine of formula (I) takes place in general with an excellent yield. This is because all the converted amine gives the corresponding alkylamine.

(37) All the results obtained in the experimental part show that the preparation of alkylamines by the method of the invention is sufficiently flexible to effectively convert a large variety of amines into alkylamines.