Syntheses of N-heterocyclic carbenes and intermediates therefor

Patent metadata

Field	Value
Publication number	US-9890125-B2
Application number	US-201414759595-A
Country	US
Kind code	B2
Filing date	Jan 6, 2014
Priority date	Jan 8, 2013
Publication date	Feb 13, 2018
Grant date	Feb 13, 2018

Abstract

A method of preparing a 2,6 disubstituted anilines includes, reacting a 2-amino isophthalic acid diester with sufficient Grignard reagent R 2 CH 2 MgX to form the corresponding diol product, dehydrating the diol product to the corresponding dialkene; and hydrogenating the diol product to form the corresponding aniline. The 2,6 disubstituted anilines can be used to produce N-Heterocyclic Carbenes (NHCs). The NHCs can find application in various fields such as organic synthesis, catalysis and macromolecular chemistry. Palladium catalysts containing the NHCs are also described.

First claim

The invention claimed is:

1. A method of preparing an at least 2,6 disubstituted aniline, the method comprising: reacting a 2-amino isophthalic acid diester with sufficient Grignard reagent R 2 CH 2 MgX to form the corresponding diol product,
wherein X is chloride, bromide or iodide, and R 2 is selected from H, methyl, ethyl, n-propyl and

wherein either R 3 is H and R 4 is alkyl that may be substituted, or
each of R 3 , R 4 are an independently selected alkyl that may be substituted;
dehydrating the diol product to the corresponding dialkene; and
hydrogenating the dialkene product to form the corresponding aniline.

2. The method of claim 1 , wherein the 2-amino isophthalic acid diester has H in the meta and para positions to provide an aniline of general formula I, wherein the groups Z 1 , Z 2 , and Z 3 are H:

3. The method of claim 2 , further comprising substitution of one or more of the H groups Z 1 , Z 2 , and Z 3 with a substituent independently selected from the group consisting of: —I, —CF 3 , —OR 6 , —R 6 and —NR 7 2 ;
wherein each group R 5 , R 6 or R 7 is independently selected from the group consisting of alkyl that may be unsaturated, substituted alkyl that may be unsaturated, aryl, substituted aryl, aralkyl and substituted aralkyl.

4. The method of claim 3 , wherein Z 1 , and Z 3 are H and Z 2 is selected from the group consisting of —I, —CF 3 , —OR 5 , —R 6 and —NR 7 2 .

5. The method according to claim 1 , wherein the 2-amino isophthalic acid diester is of formula X:

wherein each group R 1 is independently selected from the group alkyl, benzyl and substituted benzyl.

6. The method of claim 1 , wherein the 2-amino isophthalic acid diester has a substituent Z provided in one or more of the positions meta or para to the amino group;
wherein each Z is independently selected from the group consisting of —I, —CF 3 , —OR 5 , —R 6 and —NR 7 2 , wherein each group R 5 , R 6 or R 7 is independently selected from the group consisting of: alkyl that may be unsaturated, substituted alkyl that may be unsaturated, aryl, substituted aryl, aralkyl and substituted aralkyl.

7. The method of claim 1 , wherein the 2-amino isophthalic acid diester is of general formula Xa:

wherein each group Z 1 , Z 2 and Z 3 is independently selected from the group consisting of —H, —I, —CF 3 , —OR 5 , —R 6 and —NR 7 2 , wherein each group R 5 , R 6 or R 7 is independently selected from the group consisting of alkyl that may be unsaturated, substituted alkyl that may be unsaturated, aryl, substituted aryl, aralkyl and substituted aralkyl.

8. The method of claim 1 , wherein the dehydration of the diol product is by use of sulfuric acid.

9. The method of claim 1 , wherein the hydrogenation of the dialkene is by H 2 in the presence of a catalyst.

10. The method of claim 1 , further comprising preparation of the 2-amino isophthalic acid diester by:
the bis-oxidation of 2-nitro-m-xylene to 2-nitroisophthalic acid;
the conversion of 2-nitroisophthalic acid to a corresponding nitro diester; and
the reduction of the nitro diester to the 2-amino isophthalic acid diester.

11. The method of claim 10 , wherein the bis-oxidation of 2-nitro-m-xylene to 2-nitroisophthalic acid is by means of alkaline potassium permanganate.

12. The method of claim 10 , wherein the reduction of the nitro diester to the 2-amino isophthalic acid diester is by H 2 in the presence of a catalyst.

13. The method of claim 1 , wherein R 2 is selected from H, methyl, ethyl and n-propyl.

14. An aniline of formula VII or formula VIII:

Assignees

• Univ Court Univ St Andrews

Inventors

• Nolan Steven P
• Meiries Sebastien

Classifications

• C07C215/68

  having amino groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton · CPC title

• C07C213/00

  Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton · CPC title

• C07C209/68

  from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton · CPC title

• C07C209/70

  by reduction of unsaturated amines · CPC title

• C07D233/58 Primary

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms · CPC title