Methods for hydrodealkenylation
The present disclosure pertains to new methods of performing a hydrodealkenylation of monounsaturated alcohols, thiols, and derivatives thereof, such as terpenes and derivatives, comprising ozonolysis and quenching using a sulfinic acid or sulfinic acid salt.
1. A method of making a compound according to Formula 1:
wherein n is an integer from 0-5; X is O or S; R 3 is selected from H, C 1-6 alkyl, and C 2-10 acyl; and each of R 1 , R 2 , R 4 , R 5 , and R 6 are independently selected from H and C 1-10 alkyl, optionally wherein each of said C 1-10 alkyl is further substituted by a group selected from C 1-6 alkyl, hydroxy, C 1-6 alkoxy, formyl, and C 2-10 acyl, or wherein R 1 and R 2 , and/or R 4 and R 5 , and/or R 2 and R 5 , can be taken together to form a C 3-8 carbocyclic ring, wherein such ring is optionally substituted by a group selected from C 1-6 alkyl, hydroxy, C 1-6 alkoxy, formyl, and C 2-10 acyl;
wherein the method comprises the steps of (a) treating the compound of Formula 2,
wherein n, X, and each of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as defined for Formula 1, and
wherein Z is selected from vinyl (—CH═CH 2 ) and isopropenyl (—C(CH 3 )═CH 2 );
with ozone to form an ozonide mixture, and (b) quenching the ozonide mixture with an alpha-hydroxysulfinic acid or alpha-hydroxysulfinic acid salt quenching agent to yield the compound of Formula 1.
2. The method of claim 1 , wherein the quenching agent is an alpha-hydroxysulfinic acid or alpha-hydroxysulfinic acid salt according to the formula:
wherein R is H, methyl, formyl or acetyl,
wherein R is H or methyl,
wherein R 7 and R 8 are each independently selected from C 1-6 alkyl, aryl, and heteroaryl, and wherein M is a metal or ammonium counterion.
3. The method of claim 1 , wherein the quenching agent is HOCH 2 S(O)OH or HOCH 2 S(O)OM, wherein M is selected from Li, Na and K.
4. The method of claim 1 , wherein the quenching agent is HOCH 2 S(O)ONa.
5. The method of claim 1 , wherein X is S.
6. The method of claim 1 , wherein X is O.
7. The method of claim 1 , wherein R 3 is selected from H, methyl, formyl, acetyl, propionyl, butyryl, and pentanoyl.
8. The method of claim 7 , wherein R 3 is H.
9. The method of claim 1 , wherein each of R 1 , R 2 , R 4 , R 5 , and R 6 are independently selected from H and C 1-6 alkyl, optionally wherein each of said C 1-6 alkyl is further substituted by C 1-4 alkyl, hydroxy, C 1-3 alkoxy, formyl, or C 2-6 acyl.
10. The method of claim 1 , wherein R 1 and R 2 and/or R 4 and R 5 are taken together to form a C 3-8 carbocyclic ring, wherein such ring is optionally substituted by C 1-6 alkyl, hydroxy, C 1-6 alkoxy, formyl, or C 2-10 acyl.
11. The method of claim 1 , wherein R 2 and R 5 are taken together to form a C 3-8 carbocyclic ring, wherein such ring is optionally substituted by C 1-6 alkyl, hydroxy, C 1-6 alkoxy, formyl, or C 2-10 acyl.
12. The method of claim 1 , wherein the compound of Formula 1 is selected from the group consisting of:
wherein R is H, methyl, ethyl, formyl or acetyl; and wherein in each of said compounds any stereogenic center can have any permitted stereochemical arrangement or combination thereof.
13. The method of claim 1 , wherein the compound of Formula 2 is selected from citronellol, isocitronellol, dihydromyrcenol, and isopulegol.
14. The method of claim 1 , wherein step (a) comprises treating the compound of Formula 2 with ozone in a carrier gas in a solvent selected from water, propanol, isopropanol, n-butanol, s-butanol, t-butanol, acetic acid, propionic acid, butyric acid, formic acid, n-propyl acetate, isopropyl acetate, n-butyl acetate, t-butyl acetate, ethyl propionate, propyl propionate, butyl propionate, methyl butyrate, ethyl butyrate, hexane, cyclohexane, heptane, octane, and any mixture thereof, or neat in the compound of Formula 2, optionally at a concentration of 1-15% ozone in the carrier gas.
15. The method of claim 14 , wherein the solvent for step (a) is selected from water, isopropanol, n-butanol, acetic acid, propionic acid, butyric acid, formic acid, n-propyl acetate, isopropyl acetate, n-butyl acetate, cyclohexane, heptane, octane, and any mixture thereof.
16. The method of claim 1 , wherein step (a) provides a crude product stream which passes directly into a batch reactor or flow reactor for step (b).
17. The method of claim 16 , wherein the crude product stream provided by step (a) is continuously quenched by adding a solution of the alpha-hydroxysulfinic acid or alpha-hydroxysulfinic acid salt in water to the crude product stream from step (a), optionally wherein the aqueous quench solution further comprises a co-solvent or buffer.
18. The method of claim 17 , wherein the buffer is an inorganic basic salt selected from an alkali metal acetate or alkali metal phosphate, or alkali metal carbonate or bicarbonate.
19. The method of claim 1 , wherein the method further comprises the step of treating a compound of Formula 1 wherein R 3 is H with an acylating agent and a base in a solvent to form the compound of Formula 1 wherein R 3 is C 2-10 acyl; or wherein the method further comprises the step of treating a compound of Formula 1 wherein R 3 is formyl with a base in a solvent to form the compound of Formula 1 wherein R 3 is H.