Process for the preparation of diaminobutane

Abstract

The present invention relates to a process for the preparation of diaminobutane from ornithine, comprising steps of: i. preparing a solution of (a) a salt of ornithine and an acid; and (b) an aldehyde or a ketone, or a mixture thereof; in (c) a solvent, wherein the solvent comprises a protic organic solvent or a dipolar aprotic organic solvent, or a mixture thereof and ii. heating the solution to a temperature above 100 C., thereby inducing decarboxylation of the ornithine and formation of diaminobutane.

Claims

1. A process for preparing diaminobutane from ornithine, comprising steps of: (i) preparing a reaction solution comprised of: (a) a salt of ornithine and an acid; and (b) an aldehyde, a ketone or a mixture thereof; in (c) a solvent which comprises a dipolar aprotic organic solvent, and (ii) heating the reaction solution to a temperature above 100 C. thereby inducing decarboxylation of the ornithine and formation of diaminobutane.

2. The process according to claim 1, wherein the salt of ornithine is a salt of ornithine and an acid selected from the group consisting of hydrogen bromide, hydrogen chloride, hydrogen sulfate, hydrogen phosphate and hydrogen nitrate.

3. The process according to claim 2, wherein step (i) comprises dissolving ornithine and an acid in the solvent to obtain a salt solution.

4. The process according to claim 1, wherein the solvent comprises the dipolar aprotic organic solvent in an amount of at least 50 wt. %, relative to the total weight of the solvent.

5. The process according to claim 1, wherein the solvent has a boiling temperature, measured at 0.1 MPa, of at least 150 C.

6. The process according to claim 1, wherein step (ii) comprises heating the reaction solution to a temperature which is in a range of 140-250 C.

7. The process according to claim 1, wherein the dipolar aprotic organic solvent has a dielectric constant of at least 10, determined by the method according to ASTM D924, at 20 C.

8. The process according to claim 1, wherein the dipolar aprotic organic solvent is selected from the group consisting of dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile, dimethyl acetamide, and mixtures thereof.

9. The process according to claim 1, wherein the solvent further comprises a protic organic solvent selected from the group consisting of alcohols.

10. The process according to claim 9, wherein the protic organic solvent is selected from the group consisting of benzyl alcohol, cyclohexanol and mixtures thereof.

11. The process according to claim 1, wherein the aldehyde is p-methoxybenzaldehyde.

12. The process according to claim 1, wherein the ketone is 2-cyclohexenone.

13. The process according to claim 1, wherein the aldehyde, ketone or mixture thereof is present in the reaction solution in an amount within a range of 0.01-0.50 mol %, relative to the molar amount of the ornithine salt.

14. The process according to claim 1, wherein the salt of ornithine and acid is present in an amount within a range of 2-50 wt. %, relative to the total weight of the reaction solution.

15. A process for preparing diaminobutane from omithine, comprising steps of: (i) preparing a reaction solution comprised of: (a) a salt of ornithine and an acid; and (b) p-methoxybenzaldehyde; in (c) a solvent which comprises a protic organic solvent, a dipolar aprotic organic solvent or a mixture thereof, and (ii) heating the reaction solution to a temperature above 100 C. thereby inducing decarboxylation of the omithine and formation of diaminobutane.

16. The process according to claim 15, wherein the salt of omithine is a salt of ornithine and an acid selected from the group consisting of hydrogen bromide, hydrogen chloride, hydrogen sulfate, hydrogen phosphate and hydrogen nitrate.

17. The process according to claim 16, wherein step (i) comprises dissolving ornithine and an acid in the solvent to obtain a salt solution.

18. The process according to claim 15, wherein the solvent comprises the protic organic solvent, the dipolar aprotic organic solvent or the mixture thereof in an amount of at least 50 wt. %, relative to the total weight of the solvent.

19. The process according to claim 15, wherein the solvent has a boiling temperature, measured at 0.1 MPa, of at least 150 C.

20. The process according to claim 15, wherein step (ii) comprises heating the reaction solution to a temperature which is in a range of 140-250 C.

21. The process according to claim 15, wherein the dipolar aprotic organic solvent has a dielectric constant of at least 10, determined by the method according to ASTM D924, at 20 C.

22. The process according to claim 15, wherein the solvent comprises a dipolar aprotic organic solvent selected from the group consisting of dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile, dimethyl acetamide, and mixtures thereof.

23. The process s according to claim 15, wherein the solvent comprises a protic organic solvent selected from the group consisting of alcohols.

24. The process according to claim 15, wherein the solvent is selected from the group consisting of dimethylsulfoxide (DMSO), benzyl alcohol, cyclohexanol and mixtures thereof.

Description

EXPERIMENTS

(1) An amount of the salt of ornithine and hydrogen chloride was weighted into a small reaction vessel equipped with a reflux cooler, an aliquot of the solvent and a small amount of aldehyde or ketone was added. The resulting solution was heated under atmospheric pressure and kept under reflux of the solvent. The conversion of the ornithine decarboxylation was followed by thin layer chromatography. The diaminobutane formation and presence or absence of side products by ring closure reaction were confirmed by thin layer chromatography and reference samples.

(2) The solvents used in the experiments, and some properties thereof, are listed in the table 3 and 4 below. The components and the amounts thereof in the various experiments, as well as the reaction conditions and results obtained have been collected in Table 5.

(3) TABLE-US-00003 TABLE 3 Protic solvents Boiling Abbreviation Name Temperature ( C.) CH cyclohexanol 161 BA Benzylalcohol 205

(4) TABLE-US-00004 TABLE 4 Aprotic solvents: Relative Dielectric Boiling Abbreviation Name constant Temperature ( C.) DMSO dimethylsulfoxide 48.9 189 DG diglyme 7.3 162

(5) The results show that with the use of a solvent with sufficient polarity a good conversion is obtained, in contrast with a relatively apolar solvent like diglyme. Also the addition of triethanolamine does not help to catalyse the desired reaction.

(6) TABLE-US-00005 TABLE 5 Overview of Examples and Comparative Experiments. Examples/ Ornithine. Comparative HCl salt Mol Catalyst Mol Mol % Amount TEA.sup.b) T Hours Experiments (g) (*10.sup.3) (l) (*10.sup.3) cat. Solvent.sup.d) (l) (l) ( C.) reflux Result.sup.c) CHA.sup.a) E-I 0.5 3 50 0.52 17.3 CH 5 reflux 20 Mix Ornithine/DAB E-II reflux 44 100% DC: 100% DAB E-III 0.5 3 28 0.29 9.7 BA 5 reflux 1.5 100% DC: 100% DAB E-IV 0.5 3 28 0.29 9.7 BA 5 410 reflux 100% DC: DAB + RP E-V 0.25 1.5 14 0.146 9.7 DMSO 2.05 190 1.5 100% DC AA.sup.a) E-VI 0.5 1.5 28 0.18 6.1 BA 5 reflux 24 100% DC CHA.sup.a) CE-A 0.5 3 50 0.52 17.3 DG 5 410 reflux 23 No reaction CE-B 0.5 3 50 0.52 17.3 DG 5 reflux 20 No reaction Ornithine CHA CE-C 0.5 3.8 50 0.52 13.7 CH 5 reflux 19 Primarily RP CE-D 0.5 3.8 50 0.52 13.7 BA 5 reflux 19 Primarily RP CE-E 0.39 3.0 50 0.52 17.3 CH 5 reflux 19 Primarily RP CE-F 0.39 3.0 50 0.52 17.3 BA 5 reflux 19 Primarily RP .sup.a)CHA = cyclohexenon; AA = p-Anisaldehyde .sup.b)TEA = triethanolamine; .sup.c)RP = ring closed product = 6-aminopiperidin-2-one