Process for the preparation of primary amines
Process for the preparation of primary amines of formula (I): where R3 represents an alkyl, cycloalkyl or aralkyl group, by reaction of a triazolium salt of formula (II): where R1 and R2 represent hydrogen or an alkyl, aralkyl or aryl group, R4 represents an alkyl or aralkyl group or a residue of an organic polymer functionalized by an alkylating group, and A − represents a halogen, alkylsulphonate, arylsulphonate, alkyl sulphate, hydrogensulphate, hemisulphate, perchlorate or hydroxide, with a hydride, in order to obtain an amine of formula (I), which is isolated, if desired, and intermediates.
1. A process for the preparation of a primary amine of formula (I):
wherein
R3 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more hydroxyl groups, amino groups, alkoxy groups including from 1 to 6 carbon atoms or aryl groups including from 6 to 10 carbon atoms, the aryl groups optionally being substituted by one or more linear or branched alkyl groups including from 1 to 6 carbon atoms or by one or more alkoxy groups including from 1 to 6 carbon atoms or by one or more phenyl groups,
a cycloalkyl group including from 5 to 7 carbon atoms optionally substituted by one or more linear or branched alkyl groups including from 1 to 6 carbon atoms or by one or more alkoxy groups including from 1 to 6 carbon atoms,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more linear or branched alkyl groups including from 1 to 6 carbon atoms, by one or more alkoxy groups including from 1 to 6 carbon atoms or by one or more phenyl groups,
comprising the step of reacting a triazolium salt of formula (II):
wherein
R1 and R2, are identical or different, and are
hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, —(OCH 2 CH 2 O) n R′″ groups wherein n is an integer ranging from 1 to 4 and R′″ is a linear or branched alkyl group including from 1 to 4 carbon atoms, —O-aryl groups including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, or —O-aralkyl groups including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups;
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups;
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
R4 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by a —COOH radical or a —COOR′″ group in which R′″ represents a linear or branched alkyl radical including from 1 to 4 carbon atoms,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, a linear or branched alkyl groups including from 1 to 6 carbon atoms, a —COOH radical or a —COOR′″ group wherein R′″ represents a linear or branched alkyl radical including from 1 to 4 carbon atoms,
a residue of an organic polymer functionalized by an alkylating group,
A is
a halogen,
an alkylsulphonate group including from 1 to 6 carbon atoms optionally substituted by one or more halogen groups,
an arylsulphonate group including from 6 to 10 carbon atoms optionally substituted by one or more halogen groups or linear or branched alkyl groups including from 1 to 4 carbon atoms,
an alkyl sulphate group including from 1 to 6 carbon atoms,
a hydrogen sulphate group,
a hemisulphate group,
a perchlorate group, or
a hydroxide group,
with a hydride, to obtain the amine of formula (I).
2. The process according to claim 1 , wherein the R3 group comprises an asymmetric carbon α to the nitrogen.
3. The process according to claim 1 , wherein the triazolium salt of formula (II) is of the formula (IIa):
wherein
R5 is
a hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
R6 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aminotriazolium group of formula
wherein
R7 is
a hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, or
R5 and R6 can form, together with the carbon atom to which they are bonded, a ring comprising 5 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
with the proviso that the carbon carrying the R5, R6 and R7 radicals must be asymmetric.
4. The process according to claim 3 , wherein the compound of formula (IIa) is prepared by reaction of a compound of formula (III):
with an agent for the quaternization of a nitrogen, to produce the compound of formula (IIa).
5. The process according to claim 3 , wherein the compound of formula (IIa) is prepared by reaction of a compound of formula (IIIa):
wherein
R′1 and R′2 are
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, or
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, and
R″ represents
hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
a —(CH 2 CH 2 O) n R′″ group in which n represents an integer ranging from 1 to 4 and R′″ is a linear or branched alkyl group including from 1 to 4 carbon atoms,
with an agent for the quaternization of a nitrogen, to produce the compound of formula (IIa).
6. The process according to claim 5 , wherein the compound of formula (IIIa) is prepared by reaction of an organometallic compound of formula
R7-M
wherein M is an MgX or CeX 2 group in which X represents a halogen atom or M represents a metal,
with a compound of formula (IV)
with the proviso that, when R″ is a hydrogen, at least one of R5 and R6 is an aryl group optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
to produce the compound of formula (IIIa).
7. The process according to claim 6 , wherein the compound of formula (IV) is prepared by etherification and reaction of a compound of formula (V):
with a compound of formula
O═CR5R6
to produce the compound of formula (IV).
8. The process according to claim 7 , wherein the etherification takes place before the reaction of the compound of formula (V) with the compound of formula O═CR5R6.
9. The process according to claim 7 , wherein the etherification takes place after the reaction of the compound of formula (V) with the compound of formula O═CR5R6, with the proviso that at least one of R5 and R6 represents an aryl group optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups.
10. The process according to claim 5 , wherein the compound of formula (IIIa) is prepared by reduction by the action of a metal hydride on a compound of formula (IV)
or by hydrogenation of the compound of formula (IV), with the proviso that R5 cannot be hydrogen.
11. An intermediate for preparing an amine of formula H 2 N—CHR6R7, wherein
R6 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aminotriazolium group of formula
wherein R1 and R2, are identical or different, and are
hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, —(OCH 2 CH 2 O) n R′″ groups wherein n is an integer ranging from 1 to 4 and R′″ is a linear or branched alkyl group including from 1 to 4 carbon atoms, —O-aryl groups including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, or —O-aralkyl groups including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups:
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups;
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
R4 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by a —COOH radical or a —COOR′″ group in which R′″ represents a linear or branched alkyl radical including from 1 to 4 carbon atoms,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, a linear or branched alkyl groups including from 1 to 6 carbon atoms, a —COOH radical or a —COOR′″ group wherein R′″ represents a linear or branched alkyl radical including from 1 to 4 carbon atoms, or
a residue of an organic polymer functionalized by an alkylating group, and
A is
a halogen,
an alkylsulphonate group including from 1 to 6 carbon atoms optionally substituted by one or more halogen groups,
an arylsulphonate group including from 6 to 10 carbon atoms optionally substituted by one or more halogen groups or linear or branched alkyl groups including from 1 to 4 carbon atoms,
an alkyl sulphate group including from 1 to 6 carbon atoms,
a hydrogen sulphate group,
a hemisulphate group,
a perchlorate group, or
a hydroxide group,
R7 is
a hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
wherein the intermediate is selected from the group consisting of:
4-[(R)-1-Ethyl-2,2-dimethoxyethylamino]-(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazole
4-[(S)-1-Ethyl-2,2-dimethoxyethylamino]-(S,S)-3,5-bis(1-ethoxyethyl)-1,2,4-triazole
4-[(R)-1-Ethyl-2,2-dimethoxyethylamino]-(S,S)-3,5-bis(1-ethoxyethyl)-1,2,4-triazole
4-(1-Phenyl-2,2-dimethoxyethylamino)-(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazole
4-(1-Ethyl-2,2-dimethoxyethylamino)-(S,S)-3,5-bis(1-(2-methoxyethyl)ethyl)-1,2,4-triazole
4-(1-Ethylbutylamino)-(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazole
4-(1-Ethylisobutylamino)-(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazole
4-(1-Phenylpropylamino)-(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazole
4-(1-Phenylethylamino)-(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazole and
(Hexyl-3,4-diamino)-4,4′-bis[(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazole].
12. An intermediate for preparing an amine of formula H 2 N—CR5R6R7 wherein
R5 is
a hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
R6 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aminotriazolium group of formula
wherein R1 and R2, are identical or different, and are
hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, —(OCH 2 CH 2 O) n R′″ groups wherein n is an integer ranging from 1 to 4 and R′″ is a linear or branched alkyl group including from 1 to 4 carbon atoms, —O-aryl groups including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, or —O-aralkyl groups including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups;
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups;
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
R4 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by a —COOH radical or a —COOR′″ group in which R′″ represents a linear or branched alkyl radical including from 1 to 4 carbon atoms,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, a linear or branched alkyl groups including from 1 to 6 carbon atoms, a —COOH radical or a —COOR′″ group wherein R′″ represents a linear or branched alkyl radical including from 1 to 4 carbon atoms, or
a residue of an organic polymer functionalized by an alkylating group, and
A is
a halogen,
an alkylsulphonate group including from 1 to 6 carbon atoms optionally substituted by one or more halogen groups,
an arylsulphonate group including from 6 to 10 carbon atoms optionally substituted by one or more halogen groups or linear or branched alkyl groups including from 1 to 4 carbon atoms,
an alkyl sulphate group including from 1 to 6 carbon atoms,
a hydrogen sulphate group,
a hemisulphate group,
a perchlorate group, or
a hydroxide group,
R7 is
a hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, or
R5 and R6 can form, together with the carbon atom to which they are bonded, a ring comprising 5 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
wherein the intermediate is selected from the group consisting of:
N-[(S,S)-3,5-Bis(1-methoxyethyl)-1,2,4-triazol-4-yl]-2,2-dimethoxyethylimine
N-[(S,S)-3,5-Bis(1-methoxyethyl)-1,2,4-triazol-4-yl]butylimine
N-[(S,S)-3,5-Bis(1-methoxyethyl)-1,2,4-triazol-4-yl]isobutylimine
N-[(S,S)-3,5-Bis(1-methoxyethyl)-1,2,4-triazol-4-yl]-1-(ethoxycarbonyl)methylimine
N-[(S,S)-3,5-Bis(1-methoxyethyl)-1,2,4-triazol-4-yl]-1-phenylethylimine
N-[(S,S)-3,5-Bis(1-methoxyethyl)-1,2,4-triazol-4-yl]-1-methyl-2,2-dimethoxyethylimine
Bis[N-[(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazol-4-yl]methylimine]
N-[(S,S)-3,5-Bis(1-ethoxyethyl)-1,2,4-triazol-4-yl]-2,2-dimethoxyethylimine, and
N-[(S,S)-3,5-Bis(1-(2-methoxyethoxy)ethyl)-1,2,4-triazol-4-yl]-2,2-dimethoxyethylimine.
13. The process according to claim 4 , wherein the stereoisomers of formula (III) are separated by high performance liquid chromatography.
14. The process according to claim 3 , wherein the diastereoisomers of formula (IIa) are separated by crystallization.
15. An enantiomerically pure diastereoisomer of a compound of formula (IIa)
wherein
R1 and R2, are identical or different, and are
hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, —(OCH 2 CH 2 O) n R′″ groups wherein n is an integer ranging from 1 to 4 and R′″ is a linear or branched alkyl group including from 1 to 4 carbon atoms, —O-aryl groups including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, or —O-aralkyl groups including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups;
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups;
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
R4 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by a —COOH radical or a —COOR′″ group in which R′″ represents a linear or branched alkyl radical including from 1 to 4 carbon atoms,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, a linear or branched alkyl groups including from 1 to 6 carbon atoms, a —COOH radical or a —COOR′″ group wherein R′″ represents a linear or branched alkyl radical including from 1 to 4 carbon atoms,
a residue of an organic polymer functionalized by an alkylating group,
A is
a halogen,
an alkylsulphonate group including from 1 to 6 carbon atoms optionally substituted by one or more halogen groups,
an arylsulphonate group including from 6 to 10 carbon atoms optionally substituted by one or more halogen groups or linear or branched alkyl groups including from 1 to 4 carbon atoms,
an alkyl sulphate group including from 1 to 6 carbon atoms,
a hydrogen sulphate group,
a hemisulphate group,
a perchlorate group, or
a hydroxide group,
R5 is
a hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
R6 is
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
R7 is
a hydrogen,
a linear or branched alkyl group including from 1 to 6 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms, hydroxyl groups or amino groups,
a cycloalkyl group including from 3 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms,
an aryl group including from 6 to 10 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups,
an aralkyl group including from 7 to 16 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms or phenyl groups, or
R5 and R6 can form, together with the carbon atom to which they are bonded, a ring comprising 5 to 7 carbon atoms optionally substituted by one or more alkoxy groups including from 1 to 6 carbon atoms or linear or branched alkyl groups including from 1 to 6 carbon atoms.
16. The enantiomerically pure diastereoisomer of a compound of formula (IIa) according to claim 15 , wherein the compound of formula (IIa) is 1-benzyl-4-[(R)-1-phenyl-2,2-dimethoxyethylamino]-(S,S)-3,5-bis(1-methoxyethyl)-1,2,4-triazolium bromide.
17. The process according to claim 1 , further comprising the step of isolating the amine of formula (I).
18. The process according to claim 4 , wherein the compound of formula (IIa) is isolated.
19. The process according to claim 5 , wherein the compound of formula (IIa) is isolated.
20. The process according to claim 6 , wherein M is Li, Cu or (½) Zn.
21. The process according to claim 6 , wherein the compound of formula (IIIa) is isolated.
22. The process according to claim 7 , wherein the compound of formula (IV) is isolated.
23. The process according to claim 5 , wherein the stereoisomers of formula (IIIa) are separated by high performance liquid chromatography.
24. The process according to claim 13 , wherein the high performance liquid chromatography is chiral high performance liquid chromatography.
25. The process according to claim 23 , wherein the high performance liquid chromatography is chiral high performance liquid chromatography.
26. The process according to claim 5 , wherein the diastereoisomers of formula (IIa) are separated by crystallization.