Method for the synthesis of khusimone

Patent metadata

Field	Value
Publication number	US-9650324-B2
Application number	US-201414902698-A
Country	US
Kind code	B2
Filing date	Jun 25, 2014
Priority date	Jul 3, 2013
Publication date	May 16, 2017
Grant date	May 16, 2017

Abstract

A novel method for synthesis of khusimone, by bringing zizanal into contact with an oxidizing reagent in the presence of a base and an organic solvent.

First claim

The invention claimed is:

1. Khusimone synthesis method by bringing together zizanal and an oxidizing reagent.

2. Method of claim 1 , wherein zizanal is brought together with an oxidizing reagent in the presence of a base.

3. Method of claim 1 , wherein zizanal is brought together with an oxidizing reagent in the presence of an organic solvent.

4. Method of claim 1 , wherein zizanal is brought together with an oxidizing reagent in the presence of a base and an organic solvent.

5. Method of claim 1 , wherein said oxidizing reagent is a peracid or peroxide, or a mixture.

6. Method of claim 1 , wherein said oxidizing reagent can be selected from hydrogen peroxide, tert-butyl hydroperoxide, di-tert-butyl peroxide, dicumyl peroxide, tert-butyl cumyl peroxide, dibenzoyl peroxide, dilauryl, di-(2,4-dichlorobenzoyl), tert-butyl hydroperoxide, cumyl, 1-phenylethyl, performic acid, peracetic acid, perpropionic acid, m-chloroperbenzoic acid, monoperphthalic acid, monopermaleic acid or trifluoroperacetic acid.

7. Method of claim 1 , wherein the molar ratio [(OR)/(Z)] between the oxidizing reagent (OR) and zizanal (Z) is between 0.1 and 50.

8. Method of claim 1 , wherein the molar ratio [(OR)/(Z)] between the oxidizing reagent (OR) and zizanal (Z) is between 0.5 and 25.

9. Method of claim 1 , wherein the molar ratio [(OR)/(Z)] between the oxidizing reagent (OR) and zizanal (Z) is between 1 and 10.

10. Method of claim 1 , wherein the molar ratio [(OR)/(Z)] between the oxidizing reagent (OR) and zizanal (Z) is equal to 6.

11. Method of claim 2 , wherein said base can be selected from sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium methanolate (MeNaO), calcium hydroxide (Ca(OH)2), lithium hydroxide (LiOH).

12. Method of claim 2 , wherein the molar ratio [(B)/(Z)] between the base (B) and zizanal (Z) is between 0.1 and 50.

13. Method of claim 2 , wherein the molar ratio [(B)/(Z)] between the base (B) and zizanal (Z) is between 0.5 and 25.

14. Method of claim 2 , wherein the molar ratio [(B)/(Z)] between the base (B) and zizanal (Z) is between 1 and 10.

15. Method of claim 2 , wherein the molar ratio [(B)/(Z)] between the base (B) and zizanal (Z) is equal to 3.

16. Method of claim 3 , wherein said solvent is selected from water, methanol, ethanol, 5 propanol, isopropanol, n-butanol, secbutanol, isobutanol, tert-butanol, tetrahydrofuran (THF), 1,4-dioxane, methyl tert-butyl ether (MTBE), diethyl ether (Et 2 O), glyme, diglyme, dichloromethane (CH 2 Cl 2 ), chloroform (CHCl 3 ), dimethylsulfoxide (DMSO), acetonitrile, ethyl acetate, isopropyl acetate, or mixtures in any proportions of these solvents.

17. Method of claim 1 , wherein the zizanal concentration in the reaction mixture is between 0.01 and 4.5M.

18. Method of claim 1 , wherein the zizanal concentration in the reaction mixture is between 0.02 and 0.07M.

19. Method of claim 1 , wherein the zizanal concentration in the reaction mixture is 0.2M.

20. Method of claim 1 , wherein the reaction is carried out at a temperature between −25° C. (13° F.) and the solvent reflux temperature.

21. Method of claim 1 , wherein an oxidation step of an 12-norzizaenol (IV)/khusimone (I) mixture obtained after the decarbonylation reaction in an oxidizing medium is involved.

22. Method of claim 21 , wherein the oxidizing step of the 12-norzizaenol (IV)/khusimone (I) mixture is carried out in the presence of an oxidizing medium (0) and an organic solvent.

23. Method of claim 22 , wherein the oxidizing medium (0) is selected from tetrapropylammonium perruthenate, manganese oxide, pyridinium chlorochromate, ceric ammonium nitrate (CAN), pyridinium dichromate, Collins reagent, chromium trioxide, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), 2,4,6-trichloro-1,3,5-triazine, DMSO, a mixture of DMSO and oxalyl chloride, a mixture of mixture of DMSO and pyridine sulfur trioxide, a mixture of DMSO and trifluoroacetic anhydride, a mixture of DMSO and acetic anhydride, a mixture of DMSO and phosphorus oxide (P 2 O 5 ), a mixture of dimethyl sulfide and N-chlorosuccinimide (Me 2 S/NCS Corey-Kim Oxidation), a mixture of H 2 O 2 and potassium bicarbonate (KHCO 3 ) (Fleming Oxidation), Dess-Martin periodinane or acetoxyiodine oxide, 2-iodoxybenzoic acid, aluminum isopropoxide, an oxidizing system containing TEMPO (2,2,6,6-Tetramethylpiperidine-1-oxyl), or tetrapropylammonium perruthenate (TPAP) and N-methylmorpholine-N-oxide and, optionally, a co-oxidant.

24. Method of claim 22 , wherein the oxidizing medium (O) is N-methylmorpholine N-oxide (NMO).

25. Method of claim 22 , wherein the organic solvent is selected from dichloromethane (DCM), diethyl ether, DMSO, toluene, tetrahydrofuran (THF), or acetone, acetonitrile, water, or a mixture in all proportions of the listed solvents, or a mixture in all proportions of the listed solvents.

Assignees

• Robertet Sa
• Univ Nice Sophia Antipolis
• Centre Nat De La Rech Scient (Cnrs)

Inventors

• Belhassen Emilie
• Baldovini Nicolas
• Filippi Jean-Jacques
• Brevard Hugues

Classifications

• C07C45/54 Primary

  of compounds containing doubly bound oxygen atoms, e.g. esters · CPC title

• C07C2103/66

  Chemistry & Metallurgy · mapped topic

• C07C49/653

  polycyclic · CPC title

• C07C2103/97

  Chemistry & Metallurgy · mapped topic

• C07C2603/97

  containing five-membered rings · CPC title