Pyridine based ionic fluoride for catalyzing indole and tetrazole formation

Patent metadata

Field	Value
Publication number	US-10577327-B2
Application number	US-201816004511-A
Country	US
Kind code	B2
Filing date	Jun 11, 2018
Priority date	Jun 11, 2018
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

A pyridine based ionic liquid with a fluoride counter anion which catalyzes Fischer indole reaction and click chemistry. Methods of preparing the ionic liquid, and methods of utilizing the ionic liquid as a catalyst to synthesize indoles/indolenines and tetrazoles are also provided.

First claim

The invention claimed is:

1. An ionic liquid, which is at least one selected from the group consisting of

2. A method of synthesizing an ionic liquid of formula (I)

or a solvate thereof, a tautomer thereof, a stereoisomer thereof, or a mixture thereof, the method comprising:
reacting a pyridine compound of formula (IV)

or a salt thereof, a solvate thereof, a stereoisomer thereof, or a mixture thereof with an alkyl halide of formula (V)

or a salt thereof, a solvate thereof, a stereoisomer thereof, or a mixture thereof to obtain a N-alkylated pyridinium halide; and
treating the N-alkylated pyridinium halide with a fluoride salt, thereby forming the ionic liquid of formula (I),
wherein in formulae (I), (IV), and (V):
R 1 and R 2 are independently selected from the group consisting of an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted arylalkyl, and an optionally substituted aryl;
R 3 is selected from the group consisting of a hydrogen, an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted arylalkyl, an optionally substituted aryl, an optionally substituted alkoxy, an optionally substituted alkanoyl, an optionally substituted aroyl, a halogen, a nitro, and a cyano;
R 4 and R 5 are independently selected from the group consisting of a hydrogen, an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted arylalkyl, and an optionally substituted aryl;
X is a chloride, a bromide, or an iodide; and
n is an integer in a range of 0-15.

3. The method of claim 2 , wherein a molar ratio of the pyridine compound of formula (IV) to the alkyl halide of formula (V) is in a range of 1:2 to 2:1.

4. The method of claim 2 , wherein the fluoride salt is at least one selected from the group consisting of transition metal fluorides, alkali metal fluorides, ammonium fluoride, and hydrogen fluoride.

5. The method of claim 2 , wherein the fluoride salt is silver fluoride.

6. A method of synthesizing an indole or indolenine, the method comprising reacting an aryl hydrazine with an alkyl ketone or an alkyl aldehyde in the presence of the ionic liquid of claim 1 , thereby forming the indole or indolenine.

7. The method of claim 6 , wherein a molar ratio of the aryl hydrazine to the alkyl ketone or the alkyl aldehyde is in a range of 1:2 to 2:1, and wherein the ionic liquid is present in an amount of 5 mol % to 40 mol % relative to moles of the aryl hydrazine.

8. The method of claim 6 , wherein the reacting is conducted at a temperature in the range of 60° C. to 120° C.

9. The method of claim 6 , wherein the indole and indolenine is at least one selected from the group consisting of

10. A method of synthesizing a tetrazole, the method comprising reacting a nitrile with an azide in the presence of the ionic liquid of claim 1 , thereby forming the tetrazole.

11. The method of claim 10 , wherein a molar ratio of the nitrile to the azide is in a range of 1:2 to 1:6, and wherein the ionic liquid is present in an amount of 10 mol % to 50 mol % relative to moles of the nitrile.

12. The method of claim 10 , wherein the reacting is conducted at a temperature in the range of 80° C. to 150° C.

13. The method of claim 10 , wherein the tetrazole is at least one selected from the group consisting of

Assignees

• Univ King Abdulaziz

Inventors

• Ghumro Sarfaraz Ali
• Alharthy Rima D
• Saleem Sana
• Al-Rashida Mariya
• Iqbal Nafees
• Ahmed Shakil
• Ali Syed Abid
• Moin Syed Tarique
• Hameed Abdul

Classifications

• C07D209/86 Primary

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system · CPC title

• B01J31/0284

  of an aromatic ring, e.g. pyridinium · CPC title

• C07D257/04

  Five-membered rings · CPC title

• B01J31/0237

  Amines · CPC title

• C07D213/74 Primary

  Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals · CPC title