Method of synthesis of 1, 4, 7, 10, 13, 16, 21, 24-octaazabicyclo [8.8.8] hexacosane (1) and 1, 4, 7, 10, 13, 16, 21, 24-octaazabicyclo [8.8.8] hexacosa, 4, 6, 13, 15, 21, 23-hexaene (2)
View Patent ↗A process for producing compound 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa, 4,6,13,15,21,23-hexaene (2) and then compound 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) from compound (2) is described. The process uses a reaction between triaminoethylamine and glyoxal in the presence of water, alcohol and tertiary amine at low temperature to produce compound 2. Then compound 1 is produced from compound 2 by reduction with an alkali metal containing ammonia as the reductant. The compounds are aza cryptands which are used to bind metals and the like for electrides, and in alkalides, medicine and water treatment, for instance.
1. A process for the preparation of 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) which comprises:
(a) reacting a mixture of tris(2-aminoethyl)amine (tren) with glyoxal in the presence of water, a water miscible solvent and a tertiary amine with cooling to a temperature of about −30° C. or less, wherein the glyoxal is added slowly to the mixture, to prepare 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) without formation of gelatinous byproducts.
2. The process of claim 1 wherein 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) is separated from the reaction mixture.
3. The process in claim 1 wherein the reaction mixture is heated to remove the solvent thereby precipitating 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) which is separated from the reaction mixture.
4. The process of claim 3 wherein the precipitated and separated 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) is recrystallized from an organic solvent in the presence of a basic salt in water that dissolves any of the byproducts.
5. The process of any one of claims 1 , 2 , 3 or 4 wherein the cooling is with dry ice.
6. A process for the preparation of 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) which comprises:
(a) reacting in a non-reactive gas atmosphere a mixture of tris(2-aminoethyl)amine (tren) with glyoxal in the presence of water, a water miscible solvent and a tertiary amine with cooling to a temperature of about −30° C. or less, wherein the glyoxal is added slowly to the mixture, to prepare 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) without formation of gelatinous byproducts;
(b) reacting compound (2) in the mixture of step (a) with an alkali metal, in isopropanol in the presence of ammonia at a temperature of about −30° C. or less to form compound (1) from compound (2);
(c) causing the second mixture to warm to room temperature with removal of the ammonia; and
(d) separating compound (1) from the reaction mixture into an organic solvent for compound (1).
7. The process of claim 6 wherein 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) is separated in step (d) by the organic solvent and water extraction so that 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) is in the organic solvent.
8. The process of claim 7 wherein the organic solvent is selected from the group consisting of toluene, isopropanol, petroleum ether, dichloromethane and mixtures thereof.
9. The process claim 6 wherein the alkali metal is sodium.
10. The process of any one of claims 6 , 7 , 8 or 9 wherein the cooling is with dry ice.
11. A process for the preparation of 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) which comprises:
(a) reacting 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) in a mixture of a lower alkanol containing 1 to 4 atoms with an alkali metal in the presence of ammonia with cooling of the mixture to a temperature of −30° C. or less to form compound (1) from compound (2);
(b) causing the mixture including compound (1) to warm with the removal of the ammonia; and
(c) separating compound (1) from the reaction mixture.
12. The process of claim 11 wherein 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) is separated by an organic solvent-water extraction so that compound (1) is in the organic solvent, and wherein the solvent is selected from the group consisting of toluene, petroleum ether, isopropanol, dichloromethane and mixtures thereof.
13. The process of claim 11 wherein the alkali metal is sodium.
14. The process of claim 11 wherein the cooling is with dry ice.
15. A process for the preparation of 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) which comprises:
(a) reacting a mixture of tris(2-aminoethyl)amine (tren) with glyoxal in the presence of water, isopropyl alcohol (i-PrOH) and triethylamine (Et 3 N) with cooling to a temperature of about −30° C. or less, wherein the glyoxal is added slowly to the mixture, to prepare 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) without formation of gelatinous byproducts.
16. The process of claim 15 wherein 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) is separated from the reaction mixture.
17. The process in claim 15 wherein the reaction mixture is heated to remove isopropyl alcohol (i-PrOH) thereby precipitating 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) which is separated from the reaction mixture.
18. The process of claim 17 wherein the precipitated and separated 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) is recrystallized from an organic solvent in the presence of a basic salt in water that dissolves byproducts.
19. The process of any one of claims 15 , 16 , 17 or 18 wherein the cooling is with dry ice.
20. A process for the preparation of 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) which comprises:
(a) reacting in a non-reactive gas atmosphere a mixture of tris(2-aminoethyl)amine (tren) with glyoxal in the presence of water, isopropyl alcohol (i-PrOH) and triethylamine (Et 3 N) with cooling to a temperature of about −30° C. or less, wherein the glyoxal is added slowly to the mixture, to prepare 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) without formation of gelatinous byproducts;
(b) reacting compound (2) in a second mixture with an alkali metal in the presence of ammonia at a temperature of about −30° C. or less to form compound (1) from compound (2);
(c) causing the second mixture to warm to room temperature with removal of the ammonia; and
(d) separating compound (1) from the reaction mixture.
21. The process of claim 20 wherein 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) is separated in step (d) by an organic solvent and water extraction, so that 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) is in the organic solvent.
22. The process of claim 21 wherein the organic solvent is selected from the group consisting of toluene, petroleum ether, isopropanol, dichloromethane and mixtures thereof.
23. The process claim 20 wherein the alkali metal is sodium.
24. The process of any one of claims 20 , 21 , 22 , or 23 wherein the cooling is with dry ice.
25. A process for the preparation of 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) which comprises:
(a) reacting 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosa-4,6,13,15,21,23-hexaene (2) in a mixture of isopropyl alcohol (i-PrOH) with an alkali metal in the presence of ammonia with cooling of the mixture to a temperature of −30° C. or less to form compound (1) from compound (2);
(b) causing the mixture including compound (1) to warm with the removal of the ammonia; and
(c) separating compound (1) from the reaction mixture.
26. The process of claim 25 wherein 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) is separated by an organic solvent-water extraction so that 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane (1) is in the organic solvent, and wherein the solvent is selected from the group consisting of toluene, petroleum ether, isopropanol or dichloromethane and mixtures thereof.
27. The process of claim 25 wherein the alkali metal is sodium.
28. The process of claim 25 wherein the cooling is with dry ice.
29. The process of claim 1 wherein the water miscible solvent is isopropanol.
30. The process of claim 6 wherein the water miscible solvent in step (a) is isopropanol.
31. The process of claim 6 wherein the water miscible solvent in step (a) is isopropanol and the alkali metal in step (b) is sodium metal.