Metal-catalyzed oxidative coupling of thiols
View Patent ↗Disclosed are methods for preparing disulfide compounds through oxidative coupling of thiol compounds. Thiols are oxidized to the corresponding disulfide compound in high yield in presence of a base and a metal salt. The method uses low catalyst loadings and provides organic disulfide compounds with little to no byproducts.
1. A method of producing a compound of formula (II)
or a salt thereof,
the method comprising contacting a thiol and a nickel salt, in the presence of a base, with oxygen; wherein each of X and Y is the same or different and selected from the group consisting of —OH, —SH, —NH 2 , halogen, —COOH, and —COOR; and wherein each of m and n is the same or different and is an integer from 1 to 16, R is C 1 -C 18 alkyl or aryl, and wherein the compound of formula (II) is unsubstituted or substituted by one or more substituents.
2. The method of claim 1 , wherein the compound of formula (II) is
3. The method of claim 1 , wherein the compound of formula (II) is
4. The method of claim 1 , wherein the compound of formula (II) is
5. The method of claim 1 , wherein the nickel salt is selected from the group consisting of nickel sulfate, nickel acetate, and a combination thereof.
6. The method of claim 1 , wherein the organic base is a tertiary amine.
7. The method of claim 1 , wherein the molar ratio of the nickel salt to thiol is about 0.0005 to 1 or less.
8. A method of producing a compound of formula (I), (II), or (III) or a salt thereof, the method comprising:
adding nitrogen to a reaction vessel comprising a thiol, a base, and a nickel salt;
adding substantially pure oxygen to the reaction vessel after the nitrogen has been added; heating the reaction vessel;
maintaining oxygen at the same pressure during reaction;
wherein oxygen is added and maintained at a pressure less than the pressure of nitrogen, and
wherein formula (I) is
wherein each of R 1 and R 2 is the same or different, and is selected from the group consisting of C 1 -C 32 alkyl, C 2 -C 32 alkenyl, C 2 -C 32 alkenyl, aryl, heteroaryl, heterocycle, C 3 -C 8 cycloalkyl, benzyl, alkylheteroaryl, and halosubstituted alkyl, or wherein R 1 and R 2 form a carbocyclic or heterocyclic ring; and wherein each of R 1 and R 2 is unsubstituted or substituted by one or more substituents,
formula (II) is
wherein each of X and Y is the same or different and selected from the group consisting of —OH, —SH, —NH 2 halogen, —COOH, and —COOR; and wherein each of m and n is the same or different and is an integer from 1 to 16, R is C 1 -C 18 alkyl or aryl, and wherein the compound of formula (II) is unsubstituted or substituted by one or more substituents, and
formula (III) is
wherein each of R 1 , R 2 , R 3 , and R 4 is the same or different, and is selected from the group consisting of C 1 -C 32 alkyl, C 2 -C 32 alkenyl, C 2 -C 32 alkynyl, aryl, heteroaryl, heterocycle, C 3 -C 8 cycloalkyl, benzyl, alkylheteroaryl, and halosubstituted alkyl, hydroxyl, alkoxy, halogen, amino, aminoalkyl, thiol, thioalkyl, carbonyl, phosphonyl, phosphoryl, sulfonyl, sulfinyl, wherein each of R 1 , R 2 , R 3 , and R 4 is unsubstituted or substituted by one or more substituents, and wherein m is 0 to 7.
9. The method of claim 8 , wherein the compound of formula (II) is produced and has the formula
wherein each of m and n is the same or different and is an integer from 1 to 12.
10. The method of claim 8 , wherein the compound of formula (II) is produced and has the formula
11. The method of claim 8 , wherein the compound of formula (II) is produced and has the formula
12. The method of claim 8 , wherein the nickel salt is selected from the group consisting of nickel sulfate, nickel acetate, and a combination thereof.
13. The method of claim 8 , wherein the reaction vessel is maintained under an oxygen pressure of from about 50 psig to about 150 psig.
14. The method of claim 8 , wherein the reaction vessel is maintained at a temperature of about 60° C. or less.
15. The method of claim 8 , wherein the compound of formula (III) is produced and has the formula
wherein m is 0 to 7.
16. The method of claim 8 , wherein the compound of formula (III) is produced and has the formula
17. The method of claim 8 , wherein the compound of formula (III) is produced and is mixed with
wherein R is C 1 -C 32 alkyl or aryl and wherein n is 1.
18. The method of claim 1 , wherein the base is an organic base.
19. The method of claim 18 , wherein the organic base is selected from triethanolamine, triethylamine, triisopropylamine, trimethylamine, tripropylamine, tributylamine, triamylamine, triphenylamine, ethyldimethylamine, diethanolamine, diethylamine, diisopropylamine, dimethylamine, dipropylamine, dibutylamine, diamylamine, diphenylamine, methylpropylamine, piperidine, pyrrolidine, morpholine, pyridine, tert-butylamine, aniline, methylamine, ethylamine, propylamine, isopropylamine, butylamine, amylamine, hexylamine, cyclohexylamine, octylamine, or a combination thereof.
20. The method of claim 18 , wherein the organic base is triethanolamine.