# US 9,751,827 B2 · Method for alkylation of amines

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- Number: US 9,751,827 B2
- Document ID: US9751827B2
- Status: Granted
- Kind: B2
- Application number: 14/772,513
- Filed: 2014-01-21
- Published: 2016-01-14
- Granted: 2017-09-05
- Earliest claimed: 2013-03-04
- Assignees: Takasago International Corporation
- Applicants: Takasago International Corporation
- Inventors: Osamu Ogata; Hideki Nara
- Web page: https://patentgrep.com/patent/US9751827B2

## CPC

- C07C 209/02: by substitution of hydrogen atoms by amino groups
- B01J 31/189: {containing both nitrogen and phosphorus as complexing atoms, including e.g. phosphino moieties, in one at least bidentate or bridging ligand}
- B01J 31/20: Carbonyls
- B01J 31/24: Phosphines {, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands}
- B01J 31/248: {Bridged ring systems, e.g. 9-phosphabicyclononane}
- C07D 213/72: Nitrogen atoms (nitro radicals C07D213/61)
- C07D 213/74: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 295/023: Preparation; Separation; Stabilisation; Use of additives
- B01J 2231/4283: using N nucleophiles, e.g. Buchwald-Hartwig amination
- B01J 2231/44: Allylic alkylation, amination, alkoxylation or analogues
- B01J 2531/0258: Flexible ligands, e.g. mainly sp3-carbon framework as exemplified by the "tedicyp" ligand, i.e. cis-cis-cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane
- B01J 2531/821: Ruthenium
- C07C 2603/74: Adamantanes
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention provides a simple, efficient, and industrially advantageous method for the alkylation of amines. The present invention relates to a production method for N-alkylamines whereby an amine is reacted with an alcohol in the presence of a ruthenium complex represented by general formula (1): RuXY(CO)(L) (wherein X and Y can be the same or different and represent a monovalent anionic ligand, and L represents a tridentate aminodiphosphine ligand).

## Claims

### Claim 1

A method for producing an N-alkylamine, comprising reacting an amine with an alcohol in the presence of a ruthenium complex represented by the following general formula (1):
RuHCl(CO)(L) (1)
wherein, the general formula (1), L represents a tridentate aminodiphosphine ligand represented by the following general formula (2):
wherein, in the general formula (2),
R1, R2, R3 and R4 may be the same or different from one another, and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, an aralkyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy group, a heterocyclic group or a substituted amino group, wherein R1 and R2 or R3 and R4 may bind to each other to form a ring together with the adjacent phosphorus atom, and said alkyl group, cycloalkyl group, aryl group, aralkyl group, alkyloxy group, cycloalkyloxy group, aryloxy group, aralkyloxy group, heterocyclic group and substituted amino group may have substituent(s); and
Q1 and Q2 may be the same or different from each other, and each represents an optionally substituted divalent alkylene group, an optionally substituted divalent cycloalkylene group or an optionally substituted divalent aralkylene group,
wherein the N-alkylamine has the following general formula (4) or (9):
R—NH—RA (4)
or
wherein, in the general formula (4) or (9),
R represents an optionally substituted hydrocarbon group, an optionally substituted aryl group or an optionally substituted heterocyclic group, and
RA represents an alkyl group, a cycloalkyl group, an aryl group, an aralkyl group, a heterocyclic group, an alkenyl group, an alkynyl group, a cycloalkenyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy group, a hydroxyl group, an alkoxycarbonyl group, a cycloalkyloxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group, an alkenyloxycarbonyl group, an alkynyloxycarbonyl group, a cycloalkenyloxycarbonyl group, a carboxamide group or an alkoxysulfonyl group, which groups may comprise substituent(s); and
wherein the amine has the following general formula (5):
RA—NH2 (5)
wherein, in the general formula (5), RA represents the same group as in the definition in the general formula (4) or (9), and
the alcohol has the following general formula (6):
R—OH (6)
wherein, in the general formula (6), R represents the same group as in the definition in the general formula (4) or (9).

### Claim 2 (depends on 1)

The production method according to claim 1, wherein L is a tridentate aminodiphosphine ligand represented by the following general formula (3):
wherein, in the general formula (3),
Ar1, Ar2, Ar3 and Ar4 may be the same or different from one another, and each represents an optionally substituted aryl group or an optionally substituted aromatic heterocyclic group.

### Claim 3 (depends on 1)

The production method according to claim 1, wherein the N-alkylamine has the general formula (4):
wherein, in the general formula (4),
RA represents an aryl group or an aromatic heterocyclic group, which groups may comprise substituent(s).

### Claim 4 (depends on 1)

The production method according to claim 1, wherein the N-alkylamine has the general formula (9):
wherein, in the general formula (9), RA represents an aryl group, or an aromatic heterocyclic group which groups may comprise substituent(s).

### Claim 5 (depends on 1)

The method according to claim 1, wherein the alcohol is a primary or secondary alcohol.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the alcohol is methanol or ethanol.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the reaction of the amine and the alcohol is conducted in the presence of a basic substance.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the basic substance is a metal alkoxide.

### Claim 9

A method for producing an N-alkylamine, comprising reacting an amine with an alcohol in the presence of a ruthenium complex represented by the following general formula (1):
RuHCl(CO)(L) (1)
wherein, the general formula (1), L represents a tridentate aminodiphosphine ligand represented by the following general formula (2):
wherein, in the general formula (2),
R1, R2, R3 and R4 may be the same or different from one another, and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, an aralkyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy group, a heterocyclic group or a substituted amino group, wherein R1 and R2 or R3 and R4 may bind to each other to form a ring together with the adjacent phosphorus atom, and said alkyl group, cycloalkyl group, aryl group, aralkyl group, alkyloxy group, cycloalkyloxy group, aryloxy group, aralkyloxy group, heterocyclic group and substituted amino group may have substituent(s); and
Q1 and Q2 may be the same or different from each other, and each represents an optionally substituted divalent alkylene group, an optionally substituted divalent cycloalkylene group or an optionally substituted divalent aralkylene group,
wherein the N-alkylamine has the following general formula (7):
wherein, in the general formula (7), RB1 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, an aralkyl group, a heterocyclic group, an alkenyl group, an alkynyl group, a cycloalkenyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy group, a hydroxyl group, an alkoxycarbonyl group, a cycloalkyloxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group, an alkenyloxycarbonyl group, an alkynyloxycarbonyl group, a cycloalkenyloxycarbonyl group, a carboxamide group or an alkoxysulfonyl group, which groups may comprise substituent(s);
RB2 represents an alkyl group, a cycloalkyl group, an aryl group, an aralkyl group, a heterocyclic group, an alkenyl group, an alkynyl group, a cycloalkenyl group, an alkyloxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy group, a hydroxyl group, an alkoxycarbonyl group, a cycloalkyloxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group, an alkenyloxycarbonyl group, an alkynyloxycarbonyl group, a cycloalkenyloxycarbonyl group, a carboxamide group or an alkoxysulfonyl group, which groups may comprise substituent(s);
wherein RB1 and RB2 may bind to each other to form a ring together with the adjacent nitrogen atom; and
R represents an optionally substituted hydrocarbon group, an optionally substituted aryl group or an optionally substituted heterocyclic group,
wherein the amine has the following general formula (8):
wherein, in the general formula (8), RB1 and RB2 each represents the same group as the definition in the general formula (7), and
the alcohol has the following general formula (6):
R—OH (6)
wherein, in the general formula (6), R represents the same group as mentioned above.

### Claim 10 (depends on 9)

The production method according to claim 9, wherein L is a tridentate aminodiphosphine ligand represented by the following general formula (3):
wherein, in the general formula (3),
Ar1, Ar2, Ar3 and Ar4 may be the same or different from one another, and each represents an optionally substituted aryl group or an optionally substituted aromatic heterocyclic group.

### Claim 11 (depends on 9)

The production method according to claim 9,
wherein, in the general formula (7), RB1 represents an aryl group or an aromatic heterocyclic group, which groups may comprise substituent(s).

### Claim 12 (depends on 9)

The method according to claim 9, wherein the alcohol is a primary or secondary alcohol.

### Claim 13 (depends on 9)

The method according to claim 9, wherein the alcohol is methanol or ethanol.

### Claim 14 (depends on 9)

The method according to claim 9, wherein the reaction of the amine and the alcohol is conducted in the presence of a basic substance.

### Claim 15 (depends on 14)

The method according to claim 14, wherein the basic substance is a metal alkoxide.