Nickel catalyst, process for preparation and use thereof

Patent metadata

Field	Value
Publication number	US-10940468-B2
Application number	US-201716083085-A
Country	US
Kind code	B2
Filing date	Mar 6, 2017
Priority date	Mar 8, 2016
Publication date	Mar 9, 2021
Grant date	Mar 9, 2021

Abstract

The present invention disclosed to a novel nickel catalyst of formula (I) process for preparation of the same and use of nickel catalyst of formula (I) for C—H bond alkylation, and benzylation of heteroarenes.

First claim

The invention claimed is:

1. A nickel catalyst of formula (I):

wherein:
R and R 1 are the same and are selected from the group consisting of alkyl, aryl, benzyl, heteroaryl; and
X is selected from the group consisting of hydrogen, halogen, OC(O)CH 3 , OC(O) t Bu, OC(O)Ph, OC(O)admantyl, OSO 2 CF 3, BF 4 , and SbF 6 .

2. The nickel catalyst of claim 1 , wherein said nickel catalyst of formula (I) is selected from the group consisting of:
a nickel catalyst of formula (I), wherein R and R 1 are ethyl and X is chloro; and
a nickel catalyst of formula (I), wherein R and R 1 are ethyl and X is OC(O)CH 3 .

3. A process for the preparation of the nickel catalyst of formula (I) of claim 1 , the process comprising:
(a) refluxing a reaction mixture of 2-bromo-N-(quinolin-8-yl) acetamide and an amino compound in a solvent for from 20 hours to 24 hours at a temperature from 60° C. to 80° C., to afford a ligand having formula (IA):

where R and R 1 are the same as in the nickel catalyst of formula (I); and
(b) adding triethylamine to a mixture of the ligand afforded in (a), a nickel compound, and a solvent, followed by refluxing the resulting reaction mixture for 3 hours to 12 hours at a temperature from 60° C. to 70° C., to afford the nickel catalyst of formula (I).

4. The process of claim 3 , wherein said amino compound is selected from diisopropyl amine, diethylamine, and dimethyl amine; and wherein said nickel compound is selected from (DME)NiCl 2 , (THF)NiBr 2, and Ni(OAc) 2, where DME is dimethoxyethane, THF is tetrahydrofuran, and OAc is acetate.

5. The process of claim 3 , wherein said solvent in (a) and (b) is selected from acetone or tetrahydrofuran (THF).

6. A process for the alkylation or benzylation of a heteroarene using a nickel catalyst according to claim 1 , the process comprising:
stirring a reaction mixture of (a)-(e):
(a) the heteroarene,
(b) an organic halide compound or a benzyl compound,
(c) the nickel catalyst of formula (I),
(d) a base, and
(e) a solvent,

at a temperature from 120° C. to 160° C. for a period of 6 hours to 36 hours, to afford either:
an alkylated heteroarene compound when (b) is the organic halide compound; or
a benzylated heteroarene compound when (b) is the benzyl compound,

wherein:
the heteroarene has formula (3):

where:
R 2 is 2-pyridine, 2-pyrimidine, 2,4-pyrazine, or 2-oxazole; and
each R 3 is hydrogen, alkyl, alkoxy, substituted alkoxy, phenoxy, halogen, or trifluoromethyl;

the organic halide compound has formula X—R 4 , where X is chlorine, bromine, or iodine and R 4 is alkyl, whereby the alkylated heteroarene compound has formula (II):

where R 2 and each R 3 are the same as in formula (3), and where R 4 is the same as in the organic halide compound; and

the benzyl compound has formula (6):

where R 4 is hydrogen, methyl, or alkoxy, whereby the benzylated heteroarene compound has formula (III):

where R 2 and R 3 are the same as in formula (3) and R 4 is the same as in formula (6).

7. The process of claim 6 , wherein said heteroarene is selected from the group consisting of 1-(pyridine-2-yl)-1H-indole, 5-methyl-1-(pyridine-2-yl)-1H-indole, 5-methoxy-1-(pyridine-2-yl)-1H-indole, 5-fluoro-1-(pyridin-2-yl)-1H-indole, 5-bromo-1-(pyridine-2-yl)-1H-indole, 1-(pyridin-2-yl)-1H-indole-5-carbonitrile, 3-methyl-1-(pyridine-2-yl)-1H-indole, 1-(pyrimidin-2-yl)-1H-indole, and 5-methoxy-1-(pyrimidin-2-yl)-1H-indole.

8. The process of claim 6 , wherein said organic halide compound is selected from the group consisting of 1-iodobutane, 1-iodopentane, 1-bromohexane, 1-bromodecane, 1-iodododecane, 1-bromotridecane, 1-bromotetradecane, 1-bromohexadecane, 1-bromooctadecane, 1-bromo-2-methylpropane, 1-bromo-3-methylbutane, (bromomethyl)cyclohexane, (2-bromoethyl)cyclohexane, 1-bromo-2,2-dimethylpropane, (3-bromopropyl)benzene, 1-(3-bromopropyl)-4-methoxybenzene, 1-chloro-4-iodobutane, 5-bromopent-1-ene, 9-(4-iodobutyl)-8a,9a-dihydro-9H-carbazole, 2-iodopropane, (1-bromoethyl)benzene, (bromoethylene)dibenzene, 2-iodobutane, bromocyclopropane, iodocyclopentane, bromocyclohexane, bromocycloheptane, and 6-bromo-1-hexene.

9. The process of claim 6 , wherein said benzyl compound is selected from the group consisting of toluene, p-xylene, m-xylene, 1-methoxy-4-methylbenzene, 1-fluoro-4-methylbenzene, 1-chloro-4-methylbenzene, 1-bromo-4-methylbenzene, ortho-xylene, 1-fluoro-2-methylbenzene, 1-chloro-2-methylbenzene, 1-bromo-2-methylbenzene, 1-methyl-2-(trifluoromethyl)benzene, mesitylene, 2,4-difluoro-1-methylbenzene, 1-methylnaphthalene, and 1-(p-tolyl)-1H-indoletoluene.

10. The process of claim 6 , wherein said base is selected from lithium bis(trimethylsilyl)amide, lithium tert-butoxide, or mixture thereof; and wherein said solvent is selected from toluene, chlorobenzene, or mixture thereof.

Assignees

• Council Scient Ind Res

Inventors

• Punji Benudhar
• Soni Vineeta

Classifications

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D209/04

  Indoles; Hydrogenated indoles · CPC title

• C07F15/045

  without a metal-carbon linkage · CPC title

• B01J31/183 Primary

  with more than one complexing nitrogen atom, e.g. phenanthroline · CPC title