# US 10,246,395 B2 · Methods of acylation with an ionic liquid catalyzing medium

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- Number: US 10,246,395 B2
- Document ID: US10246395B2
- Status: Granted
- Kind: B2
- Application number: 15/846,414
- Filed: 2017-12-19
- Published: 2018-06-21
- Granted: 2019-04-02
- Earliest claimed: 2016-12-19
- Assignees: The Board of Trustees of The University of Alabama; Reliance Industries Limited
- Applicants: The Board of Trustees of the University of Alabama; Reliance Industries Limited
- Inventors: Robin D. Rogers; Rajkumar Kore; Parasu Veera Uppara
- Web page: https://patentgrep.com/patent/US10246395B2

## CPC

- C07C 45/00: Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C 45/46: Friedel-Crafts reactions
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

Described herein are methods of acylating an aryl substrate comprising combining a substituted aryl substrate with an acylating agent in the presence of a catalyzing medium, thereby acylating the substituted aryl substrate in the para position, wherein the catalyzing medium is an ionic liquid comprising at least one cation and at least one metal halide anion.

## Claims

### Claim 1

A method of acylating an aryl substrate, comprising: combining a substituted aryl substrate with an acylating agent in the presence of a catalyzing medium, thereby acylating the substituted aryl substrate in the para position;
wherein the catalyzing medium is an ionic liquid comprising at least one cation and at least one metal halide anion, wherein the ionic liquid is a salt of the at least one cation and the at least one metal halide anion with a melting point of 150 ° C. or less, and wherein the at least one metal halide anion comprises [Al2Cl7]−;
wherein the aryl substrate comprises a compound of formula I:
wherein R5 is H, halogen, hydroxyl, substituted or unsubstituted C1-C8 alkyl, or substituted or unsubstituted C1-C8 cycloalkyl;
wherein the acylating agent comprises an acyl halide of formula II or an acid anhydride of formula III:
wherein
X is a halogen;
R6 is H, halogen, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 cycloalkyl, or substituted or unsubstituted aryl; and R7 and R8 are independently H, halogen, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 cycloalkyl, substituted or unsubstituted aryl, or wherein, as valence permits, R7 and R8, together with the atoms to which they are attached, form a 4-10membered cyclic moiety.

### Claim 2 (depends on 1)

The method of claim 1, wherein the at least one cation is an ammonium, an imidazolium, a pyridinium, a phosphonium, a sulphonium, or a combination thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the at least one cation comprises an ammonium cation of the structure NR1 R2R3R4 , wherein R1, R2, R3, and R4 are independently H, halogen, substituted or unsubstituted C1-C14 alkyl, substituted or unsubstituted C1-C8 cycloalkyl, or wherein, as valence permits, two or more of R1 , R2, R3, and R4, together with the atoms to which they are attached, form a 3-10 membered cyclic moiety.

### Claim 4 (depends on 3)

The method of claim 3, wherein R1, R2, R3, and R4 are independently H or substituted or unsubstituted C1-C14 alkyl.

### Claim 5 (depends on 1)

The method of claim 1, wherein the at least one cation comprises a phosphonium cation of the structure PR1R2R3R4, wherein R 1,R2, R3, and R4 are independently H, halogen, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C8 cycloalkyl, or wherein, as valence permits, two or more of R1, R2, R3, and R4, together with the atoms to which they are attached, form a 3-10 membered cyclic moiety.

### Claim 6 (depends on 5)

The method of claim 5, wherein R1, R2, R3, and R4 are independently H or substituted or unsubstituted C1-C20 alkyl.

### Claim 7 (depends on 1)

The method of claim 1, wherein the at least one cation comprises [AlCl2(n-methyl-2-pyrrolidone)2]+, [(CH2)13CH3P((CH2)5CH3)3]+, [HN(C2H5)3]+, or a combination thereof.

### Claim 8 (depends on 1)

The method of claim 1, wherein the catalyzing medium is an ionic liquid comprising [HN(C2H5)3][Al2Cl7], [(CH2)13CH3P((CH2)5CH3)3][Al2Cl7], [AlCl2(n-methyl-2-pyrrolidone)2][Al2Cl7], or a combination thereof.

### Claim 9 (depends on 1)

The method of claim 1, wherein R5 is substituted or unsubstituted C1-C8 alkyl.

### Claim 10 (depends on 1)

The method of claim 1, wherein the acylating agent comprises an acyl an acid anhydride of formula III:
wherein R7 and R8 are independently H, halogen, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 cycloalkyl, substituted or unsubstituted aryl, or wherein, as valence permits, R7 and R8, together with the atoms to which they are attached, form a 4-10 membered cyclic moiety.

### Claim 11 (depends on 10)

The method of claim 10, wherein R7 and R8 are independently H, halogen, hydroxyl, or substituted or unsubstituted C1-C8 alkyl.

### Claim 12 (depends on 1)

The method of claim 1, wherein the acylating agent comprises acetic anhydride.

### Claim 13 (depends on 1)

The method of claim 1, wherein the catalyzing medium is provided in an amount of from 1-50 mol % relative to the amount of acylating agent.

### Claim 14 (depends on 1)

The method of claim 1, wherein the method is performed in the absence of HF.

### Claim 15 (depends on 1)

The method of claim 1, wherein the method produces 4-isobutylacetophenone.

### Claim 16 (depends on 1)

The method of claim 1, wherein the substituted aryl substrate acylated in the para position is produced in a yield of 40% or more.

### Claim 17 (depends on 1)

The method of claim 1, wherein the method is used to produce an intermediate for the synthesis of ibuprofen.