# US 12,215,064 B2 · Compounds for chromatographic separation of rare earth elements and s-, p-, d-metals, method of separation, and use thereof

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- Number: US 12,215,064 B2
- Document ID: US12215064B2
- Status: Granted
- Kind: B2
- Application number: 17/616,340
- Filed: 2020-05-28
- Published: 2022-08-18
- Granted: 2025-02-04
- Earliest claimed: 2019-06-05
- Assignees: Ustav Organicke Chemie A Biochemie Av Cr, V.V.I.
- Applicants: Ustav Organicke Chemie A Biochemie Av Cr, V.V.I
- Inventors: Miloslav Polasek
- Web page: https://patentgrep.com/patent/US12215064B2

## CPC

- C07B 59/00: Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se}
- C07B 59/002: {Heterocyclic compounds}
- B01D 15/424: {Elution mode}
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 401/14: containing three or more hetero rings
- C07F 9/6524: having four or more nitrogen atoms as the only ring hetero atoms
- C07F 9/65583: {each of the hetero rings containing nitrogen as ring hetero atom}
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present invention relates to compounds of general formula (I), wherein —X is selected from a group consisting of H; C1 to C6, alkyl; halogen (F, Cl, Br or I); Y is selected from a group consisting of nitrogen; N-oxide; Z1, Z2, Zm, wherein m is 1 or 2, are independently selected from the group consisting of —CH2—CH2— and —CH2—CH2—CH2; A, Am, wherein m is 1 or 2, are independently selected from H; —CH2COOH; —CH2C(O)NH2; —CH2P(O)(OH)2, and n is 1 or 2; R1, R2, R3 are independently H; C1 to C6, alkyl; C1 to C6 alkyloxy; C6 to C10 aryloxy; benzyloxy; C1 to C6 alkylthio; C6, to C10 arylthio; F; Cl; Br; I; OH; SH; NH2; C1 to C6, alkylamino; di(C1 to C6, alkyl)amino; C1 to C6 acylamino; di(C1 to C6 acyl) amino; C6 to C10 arylamino; di(C6 to C10 aryl)amino; CN; OH; nitro; COORn, C(O)NHRn, C(O)N(Rn)2, wherein Rn is independently H or C1 to C10 alkyl or C6, to C10 aryl; and/or neighboring two of R1, R2, R3 together with neighboring two carbon atoms of the aromatic cycle form a six-membered ring, optionally substituted with one or more substituents independently selected from the group consisting of OH, SH, CF3, F, Cl, Br, I, C1 to C6, alkyl, C1to C6, alkyloxy, C1 to C6 alkylthio, NH2, C1 to C6 alkylamino, di(C1 to C6 alkyl)amino, NO2, COOH, COORn, C(O)NHRn, C(O)N(Rn)2, wherein Rn is WO 2020/244686 A1 independently H or C1 to C10 alkyl or C6 to C10 aryl; with the proviso that when n is 2 and all of Z1, Z2, Zm are —CH2—CH2—, then A is not —CH2COOH; for chromatographic separation of rare earth elements and/or s-, p- and d-block metals, as well as to the method of the separation of rare earth elements.

## Claims

### Claim 1

A method of chromatographic separation comprising:
providing a mixture of at least one metal ion selected from Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Pm, Sm, Sc, Tb, Tm, Yb, Y, alkaline earth metals, Al, Ga, In, Tl, Sn, Pb, Bi and transitional metals, and at least one further metal ion, wherein said further metal ion is selected from rare earth metal ions, transition metal ions, non-transition metal ions, and actinide ions,
contacting the mixture with at least one compound of general formula (I) to form a chelates;
applying the chelates to a chromatographic column; and
eluting from the chromatographic column a chelate of the at least one metal ion and a chelate of the at least one further metal ion;
wherein:
formula (I) is:
X is H, C1 to C6 alkyl, F, Cl, Br or I;
Y is N or N-oxide;
Z1, Z2, and Zm, wherein m is 1 or 2, are -CH2-CH2-or -CH2-CH2-CH2-;
A and Am, wherein m is 1 or 2, are independently H, -CH2COOH, -CH2C(O)NH2;
-CH2P(O)(OH)2, or
n is 1 or 2;
R1, R2, and R3 are independently H, C1 to C6 alkyl, C1 to C6 alkyloxy, C6 to C10 aryloxy, benzyloxy, C1 to C6 alkylthio, C6 to C10 arylthio, F, Cl, Br, I, OH, SH, NH2, C1 to C6 alkylamino, di (C1 to C6 alkyl) amino, C1 to C6 acylamino, di(C1 to C6 acyl) amino, C6 to C10 arylamino, di(C6 to C10 aryl) amino, CN, OH, nitro, COORn, C(O)NHRn, or C(O)N(Rn)2, wherein Rn is independently H, C1 to C10 alkyl, or C6 to C10 aryl;
and/or wherein any neighboring two of R1, R2, and R3 together with any neighboring two carbon atoms of the aromatic cycle form a six-membered ring, optionally substituted with one or more substituents independently selected from the group consisting of OH, SH, CF3, F, Cl, Br, I, C1 to C6 alkyl, C1 to C6 alkyloxy, C1 to C6 alkylthio, NH2, C1 to C6 alkylamino, di(C1 to C6 alkyl) amino, NO2, COOH, COORn, C(O)NHRn, or C(O)N(Rn)2, wherein Rn is independently H, C1 to C10 alkyl, C6 to C10 aryl;
with the proviso that when n is 2 and all of Z1, Z2, Zm are -CH2-CH2-, then A is not -CH2COOH.

### Claim 2 (depends on 1)

The method of claim 1,
wherein the at least one metal ion comprises Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Pm, Sm, Sc, Tb, Tm, Yb, and Y, and the
at least one further metal ion is selected from rare earth metal ions, transition metal ions, non-transition metal ions, and actinide ions.

### Claim 3 (depends on 1)

The method of claim 1 further comprising, repeating the applying and eluting steps to further separate the at least one metal ion.

### Claim 4 (depends on 1)

The method of claim 1 further comprising decomplexing with acid the chelate of the metal ion to obtain the metal ion.

### Claim 5 (depends on 1)

The method of claim 1, wherein the at least one metal ion is Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Pm, Sm, Sc, Tb, Tm, Yb, or Y.

### Claim 6 (depends on 5)

The method of claim 5, wherein the at least one further metal ion is different from the at least one metal ion and is Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Pm, Sm, Sc, Tb, Tm, Yb, or Y.

### Claim 7 (depends on 1)

The method of claim 1, wherein the at least one metal ion and the at least one further metal ion are s-, p-and d-block metals, selected from groups II.A, III.A, IV.A, V.A, I.B, II.B, and VIII.B metal.

### Claim 8 (depends on 7)

The method of claim 7, wherein the at least one metal ion and the at least one further metal ion are different and are Ca2+, Fe2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Al3+, Pb2+, or Bi3+.

### Claim 9 (depends on 1)

The method of claim 1, wherein X is H, -CH3, or Cl.

### Claim 10 (depends on 1)

The method of claim 1, wherein R1, R2, and R3 are independently H, C1to C6 alkyl, and/or neighboring two of R1, R2, R3 together with neighboring two carbon atoms of the aromatic cycle form a six-membered ring, optionally substituted with one or more substituents independently selected from the group consisting of OH, SH, CF3, F, Cl, Br, I, C1 to C6 alkyl, C1 to C6 alkyloxy, C1 to C6 alkylthio, NH2, C1 to C6 alkylamino, di(C1 to C6 alkyl) amino, NO2, COOH, COORn, C(O)NHRn, and C(O)N(Rn)2, wherein Rn is independently H or C1 to C10 alkyl or C6 to C10 aryl.

### Claim 11 (depends on 1)

The method of claim 1, wherein at most one of A and Am is H.

### Claim 12 (depends on 1)

The method of claim 1, wherein X is -CH3 or Cl, Y is N, and all of R1, R2, and R3 are H.

### Claim 13 (depends on 1)

The method of claim 1, wherein X is H, Y is N-oxide, and two of R1, R2, and R3 together with neighboring two carbon atoms of the aromatic cycle form a six-membered ring, optionally substituted with one or more substituents independently selected from the group consisting of OH, SH, CF3, F, Cl, Br, I, C1 to C6 alkyl, C1 to C6 alkyloxy, C1 to C6 alkylthio, NH2, C1 to C6 alkylamino, di(C1 to C6 alkyl) amino, NO2, COOH, COORn, C(O)NHRn, and C(O)N(Rn)2, wherein Rn is independently H or C1 to C10 alkyl or C6 to C10 aryl.

### Claim 14 (depends on 1)

The method of claim 1, wherein the compound represented by formula (I) is: 1-((4,7-bis (carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl) methyl) isoquinoline 2 oxide; 1-((4-(2-amino-2-oxoethyl)-7,10-bis (carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl) methyl) isoquinoline 2-oxide; 1-((4,10-bis (2-amino-2-oxoethyl)-7-(phosphonomethyl)-1,4,7,10-tetraazacyclododecan-1-yl) methyl) isoquinoline 2-oxide; 1,1′-((7,10-bis (carboxymethyl)-1,4,7,10-tetraazacyclododecane-1,4 diyl) bis (methylene)) bis (isoquinoline 2-oxide); 1-((1,7,10-tris (carboxymethyl)-1,4,7,10-tetraazacyclotridecan-4-yl) methyl) isoquinoline 2-oxide; 1-((4,7,10-tris (carboxymethyl)-1,4,7, 10-tetraazacyclotridecan-1-yl) methyl) isoquinoline 2-oxide; 1-((4,8,11-tris (carboxymethyl)-1,4,8,11-tetraazacyclotetradecan-1-yl) methyl) isoquinoline 2-oxide;
2,2′,2″-(11-((6-chloropyridin-2-yl) methyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-triyl) triacetic acid; 2,2′,2″-(11-((6-methylpyridin-2-yl) methyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-triyl) triacetic acid; 1-((4,7-bis (carboxymethyl)-1,4,7-triazonan-1-yl) methyl) isoquinoline 2-oxide; 1-((5,9-bis (carboxymethyl)-1,5,9-triazacyclododecan-1-yl) methyl) isoquinoline 2-oxide; or 1-((4,8,12-tris (carboxymethyl)-1,4,8, 12-tetraazacyclopentadecan-1-yl) methyl) isoquinoline 2-oxide.

### Claim 15

A compound represented by formula (Ia),
X is H, C1 to C6 alkyl, F, Cl, Br or I;
Y is N or N-oxide;
Z1, Z2, and Zm, wherein m is 1 or 2, are -CH2-CH2-or -CH2-CH2-CH2-;
A and Am, wherein m is 1 or 2, are independently H, -CH2COOH, -CH2C(O)NH2; or -CH2P(O)(OH)2, and wherein at most one of A and Am is H;
n is 1 or 2;
R1, R2, and R3 are independently H, C1 to C6 alkyl, C1 to C6 alkyloxy, C6 to C10 aryloxy, benzyloxy, C1 to C6 alkylthio, C6 to C10 arylthio, F, Cl, Br, I, OH, SH, NH2, C1 to C6 alkylamino, di(C1 to C6 alkyl) amino, C1 to C6 acylamino, di(C1 to C6 acyl)amino, C6 to C10 arylamino, di(C6 to C10 aryl)amino, CN, OH, nitro, COORn, C(O)NHRn, or C(O)N(Rn)2, wherein Rn is independently H, C1 to C10 alkyl, or C6 to C10 aryl;
and/or wherein any neighboring two of R1, R2, and R3 together with any neighboring two carbon atoms of the aromatic cycle form a six-membered ring, optionally substituted with one or more substituents independently selected from the group consisting of OH, SH, CF3, F, Cl, Br, I, C1 to C6 alkyl, C1 to C6 alkyloxy, C1 to C6 alkylthio, NH2, C6 to C10 alkylamino, di(C6 to C10 alkyl) amino, NO2, COOH, COORn, C(O)NHRn, or C(O)N(Rn)2, wherein Rn is independently H, C1 to C10 alkyl, C6 to C10 aryl;
with the proviso that:
when n is 2, all of Z1, Z2, Zm are -CH2-CH2-, then A is not -CH2COOH;
when Y is nitrogen, then X is not H; and
when n is 1, all of Z1, Z2, Zm are -CH2-CH2-, and Y is nitrogen, then X is not halogen.

### Claim 16 (depends on 15)

The compound of claim 15, wherein X is selected from a group consisting of H; -CH3 and Cl.

### Claim 17 (depends on 15)

The compound of claim 15, wherein R1, R2, R3 are independently H; C1 to C6 alkyl; and/or neighboring two of R1, R2, R3 together with neighboring two carbon atoms of the aromatic cycle form a six-membered ring, optionally substituted with one or more substituents independently selected from the group consisting of OH, SH, CF3, F, Cl, Br, I, C1 to C6 alkyl, C1 to C6 alkyloxy, C1 to C6 alkylthio, NH2, C1 to C6 alkylamino, di(C1 to C6 alkyl) amino, NO2, COOH, COORn, C(O)NHRn, C(O)N(Rn)2, wherein Rn is independently H or C1 to C10 alkyl or C6 to C10 aryl.

### Claim 18 (depends on 15)

The compound of claim 15 which is: 1-((4,7-bis (carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl) methyl) isoquinoline 2-oxide; 1-((4-(2-amino-2-oxoethyl)-7,10-bis (carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl) methyl) isoquinoline 2-oxide; 1-((4,10-bis (2-amino-2-oxoethyl)-7-(phosphonomethyl)-1,4,7,10-tetraazacyclododecan-1-yl) methyl) isoquinoline 2-oxide; 1-((1,7,10-tris (carboxymethyl)-1,4,7,10-tetraazacyclotridecan-4-yl) methyl) isoquinoline 2-oxide; 1-((4,7,10-tris (carboxymethyl)-1,4,7,10-tetraazacyclotridecan-1-yl) methyl) isoquinoline 2-oxide; 1-((4,8,11-tris (carboxymethyl)-1,4,8,11-tetraazacyclotetradecan-1-yl) methyl) isoquinoline 2-oxide; 2,2′,2″-(11-((6-chloropyridin-2-yl) methyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-triyl) triacetic acid; 2,2′,2″-(11-((6-methylpyridin-2-yl) methyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-triyl) triacetic acid; 1-((4,7-bis (carboxymethyl)-1,4,7-triazonan-1-yl) methyl) isoquinoline 2-oxide; 1-((5,9-bis (carboxymethyl)-1,5,9-triazacyclododecan-1-yl) methyl) isoquinoline 2-oxide; or 1-((4,8,12-tris (carboxymethyl)-1,4,8,12-tetraazacyclopentadecan-1-yl) methyl) isoquinoline 2-oxide.