Process for the preparation of lactams from glyoxalic acid

Patent metadata

Field	Value
Publication number	US-10377707-B2
Application number	US-201615750887-A
Country	US
Kind code	B2
Filing date	Aug 1, 2016
Priority date	Aug 20, 2015
Publication date	Aug 13, 2019
Grant date	Aug 13, 2019

Abstract

A process for the synthesis of lactams suitable for use in antimicrobial, anti-biofilm bacteriostatic compositions.

First claim

The invention claimed is:

1. A process for the synthesis of a γ-lactam, the process comprising the steps of:
(a) performing an Aldol condensation between an acetone initiator and glyoxalic acid;
(b) treating the product(s) of step (a) with an organic acid to effect dehydration;
(c) reacting the product of step (b) with ammonia or a primary amine, or salt thereof, to afford the γ-lactam.

2. The process of claim 1 , wherein the organic acid of step (b) is a sulfonic acid, optionally wherein the sulfonic acid is para-toluenesulfonic acid or methylsulfonic acid.

3. The process of claim 1 , wherein step (c) uses ammonia, optionally wherein step (c) uses concentrated aqueous ammonia.

4. The process of claim 1 , wherein the process further comprises:
(d) dehydration of the γ-lactam product of step (c) to afford a γ-lactam having an exo-methylene group.

5. The process of claim 4 , wherein step (d) uses boron trifluoride etherate.

6. The process of claim 1 , wherein process further comprises making the acetone initiator before step (a), the process comprising the steps of:
(i) reacting an aldehyde with nitroethane; and
(ii) treating the product of step (i) with a Lewis acid;

optionally wherein Lewis acid is Fe/FeCl 3 .

7. The process of claim 1 , wherein the γ-lactam is a lactam of formula (I) or (II):

wherein:
R 1 and R 2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and
R 3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl and —C(O)CR 6 ═CH2;
R 4 and R 5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and
R 6 is selected from hydrogen and methyl; and
R 7 is selected from hydrogen and —C(O)CR 6 ═CH 2 .

8. The process of claim 7 , wherein;
R 1 is hydrogen;
R 3 is hydrogen;
R 4 is hydrogen;
R 5 is hydrogen;
R 6 is hydrogen;
R 7 is hydrogen; and R 2 is aryl or aralalkyl.

9. The process of claim 7 , wherein R 2 is a phenyl group or a substituted phenyl group, optionally wherein R 2 is a mono-substituted phenyl group.

10. The process of claim 9 , wherein R 2 is selected from phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl and 4-methylphenyl.

11. The process of claim 1 , wherein the γ-lactam is a lactam selected from:

Assignees

• Conopco Inc

Inventors

• Norbury Andrew Martyn
• Thornthwaite David William

Classifications

• C07D207/44

  having three double bonds between ring members or between ring members and non-ring members · CPC title

• C07D201/08 Primary

  from carboxylic acids or derivatives thereof, e.g. hydroxy carboxylic acids, lactones or nitriles · CPC title

• C07D207/38

  2-Pyrrolones · CPC title