Methods of forming imines, imine-related and imine-derived compounds using green solvents

Patent metadata

Field	Value
Publication number	US-11565995-B2
Application number	US-202117234715-A
Country	US
Kind code	B2
Filing date	Apr 19, 2021
Priority date	Apr 17, 2020
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

The present disclosure relates to using green solvents to synthesize an array of imines, imine-related and imine-derived compounds in an efficient and eco-friendly matter, satisfying green chemistry requirements. Reaction embodiments are performed using solvents, such as ethyl lactate and dimethyl isosorbide, which are both individually characterized as green. In embodiments, solvents include lactic whey and/or water as co-solvents. In these green solvents, the synthesis process discussed herein can produce up to quantitative yields of product at room temperature in a short duration. Embodiments include a method of forming an imine, imine-related or imine-derived compound product. In embodiments, the methods include mixing an aldehyde reactant with a nucleophilic/nitrogen-containing reactant in a green solvent at a temperature between negative twenty degrees Celsius (−20° C.) and positive fifty degrees Celsius (50° C.); stirring the mixture; and forming an imine, imine-related or imine-derived compound product.

First claim

What is claimed is:

1. A method of forming an imine, imine-related or imine-derived compound product, comprising the steps of:
mixing a first reactant characterized as a carbonyl-containing compound with a second reactant characterized as a nitrogen-containing reactant in a green solvent at a temperature between negative twenty degrees Celsius (−20° C.) and fifty degrees Celsius (50° C.) to form a mixture, wherein the green solvent comprises an aqueous solution of dimethyl isosorbide or an aqueous solution of ethyl lactate;
stirring the mixture for a first duration; and
forming an imine, imine-related or imine-derived compound product.

2. The method of claim 1 , wherein the first reactant is one or more of an aldehyde, ketone, or ester.

3. The method of claim 1 , wherein the second reactant is further characterized as a nucleophilic/nitrogen-containing reactant.

4. The method of claim 1 , wherein the imine-related compound is one or more of oxime, azine, hydrazone, phenylhydrazone, or semicarbazones.

5. The method of claim 1 , wherein the first reactant is an ester and the compound product is characterized as quinoxalinone.

6. The method of claim 1 , wherein the green solvent comprises an aqueous solution of ethyl lactate over a range of concentration ratios from 60:40 to 100:0, 70:30 to 90:10, or 75:25 to 85:15 of ethyl lactate:water.

7. The method of claim 1 , wherein the green solvent further comprises an aqueous solution of ethyl lactate at a concentration ratio of 80:20 ethyl lactate:water.

8. The method of claim 1 , wherein the green solvent comprises an aqueous solution of dimethyl isosorbide over a range of concentration ratios from 85:15 to 100:0, 90:10 to 95:5, or 92:8 of dimethyl isosorbide:water.

9. The method of claim 1 , wherein the green solvent comprises an aqueous solution of ethyl lactate over a range of concentration ratios from 60:40 to 100:0, 70:30 to 90:10, or 75:25 to 85:15 of ethyl lactate:lactic whey.

10. The method of claim 9 , wherein the lactic whey is acidic whey.

11. The method of claim 1 , further comprising the steps of:
mixing the first reactant into solution in the green solvent to form a green solvent aldehyde solution, wherein the first reactant is an aldehyde reactant;
mixing the second reactant into solution in water to form an aqueous nucleophilic/nitrogen-containing solution, wherein the second reactant is a nucleophilic/nitrogen containing reactant;
mixing the green solvent aldehyde solution with the aqueous nucleophilic/nitrogen-containing solution;
stirring the green solvent aldehyde solution together with the aqueous nucleophilic/nitrogen-containing solution; and
forming an imine, imine-related or imine-derived compound product.

12. The method of claim 1 , wherein the first reactant is an aldehyde reactant comprising a substituted benzaldehyde.

13. The method of claim 1 , wherein the second reactant is a nucleophilic/nitrogen-containing reactant comprising a semicarbazide hydrochloride.

14. The method of claim 1 , wherein the first reactant is an aldehyde reactant and the second reactant is a nucleophilic/nitrogen-containing reactant, and wherein the method comprises: heating the first reactant in an aqueous solution to form a supersaturated green solvent aldehyde solution; and
mixing the second reactant into the supersaturated green solvent aldehyde solution within zero (0) to thirty (30) seconds after the first reactant is totally dissolved and completely enters solution in the green solvent.

15. A method of forming an imine, imine-related or imine-derived compound product, comprising the steps of:
mixing a first reactant characterized as a carbonyl-containing compound with a second reactant characterized as a nitrogen-containing reactant in a green solvent at a temperature between negative twenty degrees Celsius (−20° C.) and fifty degrees Celsius (50° C.) to form a mixture, wherein the green solvent comprises an aqueous solution of ethyl lactate and lactic whey;
stirring the mixture for a first duration; and
forming an imine, imine-related or imine-derived compound product.

16. The method of claim 15 , wherein the lactic whey is acidic whey.

17. The method of claim 15 , wherein the green solvent comprises an aqueous solution of ethyl lactate over a range of concentration ratios from 70:30 to 90:10, or 75:25 to 85:15 of ethyl lactate:lactic whey.

18. A solvent solution suitable for forming an imine, imine-related or imine-derived compound, or pharmaceutically acceptable salt thereof, comprising: an aqueous solution of ethyl lactate and lactic whey.

19. The solvent solution of claim 18 , wherein the aqueous solution comprises ethyl lactate over a range of concentration ratios from 70:30 to 90:10, or 75:25 to 85:15 of ethyl lactate:lactic whey.

20. The solvent solution of claim 19 , wherein the lactic whey is acidic whey or sweet whey.

Assignees

• Research Foundation For The State Univ Of New York
• Univ New York State Res Found

Inventors

• Helms Eric
• Bennett Jacqueline

Classifications

• C07D241/42 Primary

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

• C07C2601/16

  the ring being unsaturated · CPC title

• C07C249/02

  of compounds containing imino groups · CPC title

• C07D241/44

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring · CPC title

• C07C249/08 Primary

  by reaction of hydroxylamines with carbonyl compounds · CPC title