The present invention relates to new organic bisquinoline compounds with chelate forming abilities. The new compounds are intended for use as key chemicals, e.g. reagents or spe¬ cialty chemicals, in different technical processes.

An important feature of the new compounds is that they exhi¬ bit improved selectivity effects when binding to metal ions ^or ionic compounds such as solid or dissolved metal salts, minerals, and metal surfaces, when compared with previously known compounds. The improved selectivity applies especially to ions and ionic compounds of certain heavy metals, such as copper and zinc, over ions and ionic compounds of other me- tals and non-metals, such as ferrous and ferric ions. The compounds described in the present invention also exhibit selectivity for copper and zinc over cadmium, nickel, cobalt-, chromium, manganese, alkali and alkaline earth metals.

In view of the technical and economical importance of heavy metals and their impact on the environment, selective pro¬ cesses for their recovery from low grade and/or complex de¬ posits are of utmost importance.

Thus, one object of the present invention is to provide new chelate forming agents for selectively separating heavy me¬ tal ions or ionic compounds from a mixture of metal ions or ionic compounds.

Another feature is to provide a process for selectively se¬ parating heavy metal ions and ionic compounds from a mixtu¬ re of metal ions and ionic compounds.

Since the new compounds are also excellent extraction agents, further objects of the invention are to provide new extracting agents and new extracting processes based on the use of the new bisquinoline compounds of the present inven¬ tion.

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_

In particular this invention relates to processes for ex¬ tracting metal ions from aqueous solutions, e.g. from aqueous solutions obtained on recovering metals from ores and from natural, industrial or urban effluents. The pro¬ cesses involve treatment of the aqueous solution with a water immiscible organic solution of the extracting agent or reagent of the invention and subsequent separation of the aqueous phase from the organic phase containing the complexed metal ions.

The new chelate forming agents are bisquinaldic acids which may be represented, by the general formula I:

wherein R-. , R , R_ and R-, which may differ or be indenti- cal, are selected from the group consisting of hydrogen, R and OR, X is selected from the group consisting of 0 and S, and A is selected from the group consisting of (CH ) , CH ₂ CH ₂ (OCH ₂ CH ₂ ) and CH ₂ CH ₂ OCHRCH , wherein n=2-10 and p=l-3. R is a lipophilizing hydrocarbon group which may be aliphatic or aromatic, straight or branched, saturated or unsaturated.

The chelate forming agent should preferably have at least one or two lipophilizing groups R and R should be an alkyl or alkenyl group with 3-24 carbon atoms, optimally 6-18. Suitable R groups are decyl, 3-(5,5,7,7-tetrameth t-l- octenyl) and 1-(5,5,7,7-tetramethyl-2-octenyl) groups.

The total number of carbon atoms in all R groups should not exceed 40.

The following list discloses some of the compounds accor- ding to the invention which have particularly interesting properties:

1,3-bis(2-carboxy-8-quinolinylox .propane, l,3-bis[2-carboxy- 4-(1-hexyloxy)-8-quinolinyloxy]propane, 1,3-bis[2-carboxy- 4- (1-dodecyloxy)-8-quinolinyloxy]propane, 1,3-bis[2-carbo- xy-4-(l-(5,5,7,7-tetramethyl-2-octenyloxy) )-8-quinolinyloxy3- propane, 1,4-bis (2-carboxy-8-quinolinyloxy)butane, 1,8-bis- (2-carboxy-8-quinolinyloxy)octane, 1,8-bis(2-carboxy-8-qui- nolinyloxy)-3,β-dioxaoctane, 1,8-bis[2-carboxy-4-(l-(5,5,7,7- tetramethyl-2-octenyloxy) )-8-quinolinyloxy]-3,β-dioxaoctane, l,8-bis[2-carboxy-3-(1-propyl)-4- (1-(5,5,7,7-tetramethyl-2- octenyloxy) )-8-quinolinyloxy]-3,6-dioxaoctane, l,8-bis[2- carboxy-3-(3-(5,5,7,7-tetramethyl-l-octenyl) )-4-hexyloxy-8- quinolinyloxy]-3,β-dioxaoctane, 1,8-bis[2-σarboxy-5- (1- hexyloxy) 8-quinolinyloxy]-3,6-dioxaoctane, 1,8-bis[2-carbo- xy-5-(l-dodecyloxy)-8-quinolin ^* yloxy]-3,6-dioxaoctane, 1,8- bis[2-carboxy-5- (1-(5,5,7,7-tetramethyl 1-octenyloxy) )-8- quinolinyloxy]-3,β-dioxaoctane, 1,8-bis[2-carboxy-5-(l-hexyjr oxy ⁾ - 6-(5,5,7,7-tetramethyl-l-octenyl) )-8-quinolinyloxy]- 3,6-dioxaoctane, 1,11-bis (2-carboxy-8-quinolinyloxy)-3,6, 9- trioxaundecane and l,2-di[2-carboxy-4-(1-(5,5,7,7-tetra- methyl-2-octenyloxy) )-8-quinolinylthio) Jethane .

In brief, the improved selectivity of the new compounds according to the present invention can be ascribed to

a) the metal bonding groups in the reagent, that is the qui- noline nitrogen and the carbox lic oxygen, and

b) special, so called primary, structure elements, the function of which is to direct and limit the coordina¬ tion geometry of the metal complex by sterical influ¬ ence.

OMPI

In addition to the primary structure elements, the func¬ tion of which is common for all compounds according to the present invention, there are secondary structure elements which are decided by and adapted for the technical proces- ses for which the compounds are intended. The secondary structure elements modify the physical properties of the compounds such as solubility, hydrophobicity etc. , proper¬ ties determining the distribution of the compounds between different phases in multiple phase systems such as oil/ water, solid phase/liquid phase. The secondary elements are designed and positioned so that they do not interfere with the function of the primary structure elements and with the bonding ability of the compounds.

An essential feature of the structure of the compounds of the invention is the primary structure element, the flex¬ ible molecular chain joining the two quinoline nuclei in the 8-positions. This chain should be an α,ω-bisoxy or -bis- thio group with at least_ two carbon atoms.

Another essential feature of the present compounds is the lack of substituent in the 7-positions. It has been found that a substituent in this position dramatically decreases the extracting power. A possible theoretical explanation to this effect is that the substituent in the 7-position pre¬ vents complexation by sterical hindrance in the sensitive complex-binding area. The 7-positions must therefore be avoided when the secondary lipophilizing elements are intro¬ duced into the parent molecule.

The substituents in the 3-, 4-, 5- and 6-positions of the quinoline nuclei are not critical and are chosen to give sufficient lipophilicity to the reagent.

It is believed that the selectivity of the tetradentate bis¬ quinaldic acids is related to their ability to disfavour the extraction of certain hexacoordinating metal ions such

3+ ^' 2+ as Fe and Fe ions, while simultaneously enhancing the

extraction of certain tetracoordinating metal ions such as Cu 2+ and Zn2+ ions.

This discriminating effect may be rationalized by the fact that in a one-to-one complex between a hexacoordinating me¬ tal ion and a tetradentate organic reagent, only four out of six ligand sites, which are occupied by hydrophiliσ inorganic ligands in the original aquo-complex, are replaced by the lipophilizing organic reagent. Such a mixed and consequently only partially lipophilized metal ion complex is then less likely to be extracted into an organic phase relative to the fully lipophilized one-to-one complex resulting from the complexation by the same tetradentate reagent with a tetracoordinating metal ion.

The tetradentate bisquinaldic acid derivatives of the pre¬ sent invention may be obtained by hydrolysis of the corres¬ ponding dinitriles, which are prepared by alk lation of 8- hydroxyquinaldonitriles with the appropriate ditosylates or dihalides. The 8-hydroxyquinaldonitriles are synthesized from 8-hydroxyquinolines, which can be synthezised by lite¬ rature methods or are commercially available. The 8-hydroxy- quinolines are oxidized to the N-oxides, which are trans¬ formed into 8-hydroxy-l-methoxy-quinolinium methyl sulfates using dimethyl sulfate.. Reaction with sodium cyanide gives 8-hydroxy-2-cyanoquinolines.

An alternative route for the preparation of the reagents in¬ volve alkylation of 2-nitrophenols or 2-aminothiophenols with an α,ω-dihalide and, after reduction of the former to the corresponding bis-aniline compound, reaction with di- ethyl oxalacetic acid sodium salt or dimethyl acetylene di- carbox late, followed by 0-alkylation with an appropriate alkyl halide and hydrolysis of the ester groups.

The new quinaldic acids are excellent reagents for the sol¬ vent extraction of metal ions that can form a complex com¬ pound soluble in an organic solvent, in particular copper(II)

OMPI

and zinc (II) .

Any organic solvent or mixture of solvents may be used which is immiscible with water and chemically stable. Non- flam ability and low toxicicy are desirable properties.

Modifiers such as long chain aliphatic alcohols, which im¬ prove solubility, phase separation and general extraction performance may be added, suitably in amounts from 0.4 to 20% by weight of the organic solvent. Emulsification may be reduced by the addition of surface active agents such as ethylene oxide/alkyl phenyl condensates. Solubility and ex¬ traction performance may be further enhanced by using mix¬ tures of quinaldic acids with different lipophilizing sub¬ stituents R-3.-R5, and A.

Since acid is liberated during the extraction process, it may be necessary to add alkali to maintain the pH of the aqueous phase at the proper level.

Generally solutions containing from 5 to 50% by weight of the quinaldic acids are most effective. The extraction is conveniently carried out at ambient or near ambient tempera¬ tures but elevated temperatures may sometimes be required to improve the solubility of the extracted complexes.

The process of the invention may be applied to aqueous leach solutions of minerals, scrap metal or other metai-containing by-products or residues obtained by treatment thereof with acids such as sulfuric, sulfurous, hydrochloric or nitric acids. The extraction may be performed in any pH range in which the metal hydroxides are not precipitated. The pH may be chosen in such a way that only the desired metal ion is extracted; a convenient pH range is 1-5.

The process is in general particularly suitable for the re _¬ covery of metals from solutions containing at least 5 g per litre.

The liquid-liquid contacting mixture should be .mixed

intimately to obtain maximum mass transfer. It should also be given a sufficiently long setting or quiescent period to allow the phases to separate. These conditions may be ful¬ filled by using mixer-settlers, differential contactors or centrifugal separators.

To recover the extracted metal from the chelate, the orga¬ nic phase is stripped with a strong aqueous acid. The orga¬ nic phase may then be conditioned in a wash step to remove complexed acid prior to the next loading step.

Due to the dependance on a constant distribution coefficient and on proper timing for phase separation, the extraction process is essentially a steady-state process and should be run as a σontinous, rather than batch, operation. If a se¬ ries of mixer-settlers are used they should always be run with countercurrent flows for maximum efficiency.

The metal ion selectivities expressed by the present class of chelating compounds can be advantageously used in other separation processes such as liquid or solid supported mem¬ brane technique and ore flotation. The specific compounds used in these other separation methods are derived from pa¬ rent structures possessing the same primary structural ele- ments as described above, but with different secondary ele¬ ments specifically adopted for the actual process.

The invention is illustrated but not limited by the follo¬ wing examples.

Example 1

8-Hydroxγquinoline (87 g, 0.6 mol) in acetic acid (180 ml) was heated to 65-70°C. 35% H ₂ 0 ₂ (46 ml) was added and an- other two portions of 35% H ₂ 0 ₂ (2 x 36 ml) were added after 1 h 20 min and 2 h 40 min respectively. The reaction mix¬ ture was kept at 65-70°C for 5 h and then left at room tem¬ perature overnight. Evaporation of the solvent gave 117 g of an oil which was partly dissolved in CH_C1 ₂ (0.6 1). This solution was washed with 10% Na ₂ C0 ₃ (100 + 50 ml) and dried. The solvent was evaporated and the residue extracted with boiling water (0.7 + 0.3 1). 8-Hydrσxyquinoline-l-oxi- de precipitated as yellow crystals (24 g, 28%) , m.p.130-7 C

(A.N. Bhat and B.D. Jain, J. Scient. Ind. Res. 19B (1960)16 and K. Ramaiah and V.R. Srinivasan, Proc. Indian Acad. Sci. A55 (1962) 360) .

Dimethyl sulfate (4-5% excess) was added to 8-hydroxyquino- line-1-oxide, (55 g, 0.34 mol) and the mixture was heated to 75 C for 3.5 h. When the mixture was allowed to reach room temperature 8-hydroxy-l-methoxyquinolinium methyl sulfate slowly crystallized. The product was washed with ether and dissolved in water (200 ml) . This solution was added to so¬ dium cyanide (50 g, 1 mol) in water (200 ml) at -5 C during 45 min. After stirring at 0°C for a further 2 h, a 1:1 mix¬ ture of acetic acid and water (100 ml) was added. The preci¬ pitate formed was filtered off, washed with water and dried

Recrystallization of the crude product (54 g) from petroleum ether 100-125 C (1.6 1) with decolorizing carbon gave 8- hydroxyquinoline-2-carbonitrile (47 g, 0.27 mol, 80%), m.p. 134-5 C (V.M. Dziomko, J.A. Krasavin and Yu. Radin, Chem. Abstr. 65 (1966) 5437, 7139).

8-Hydroxyquinoline-2-carbonitrile (3.40 g, 20 m ol) and po- tassium carbonate (3.04 g, 22 mmol) in dimethylformamide

(DMF) (35 ml) were stirred and heated to 75°C. 1,3-propane- diol ditosylate was added during 25 min and the reaction was continued for an additional 20 h. The reaction mixture was

cooled and poured into ice-water (300 ml) . The precipipa- ted product was filtered off and recrystallized to give . l,3-bis(2-cyano-8-quinolinyloxy) propane (62%) , m.p. 221-4 C (acetone) . Anal. Calσ. for ^C ₂ 3 ^H 16 ^N 4°2 ^{: C: 72} - ⁶ ' H: 4.2, N:14.7. Found: C:73.1, H:4.2, N:14.8.

The dinitrile was hydrolyzed to the dicarboxyliσ acid by o potassium hydroxide (KOH) in aq. ethanol at 70 C until the evolution of ammonia had ceased (40 h) . The reaction mix- ture was poured into water, neutralized with 2M HCl, and the product, 1,3-bis (2-carboxy-8-quinolinyloxy) propane m.p. 181-2°C (R 418) , crystallized. Anal. Calc. for ^C 23 ^H i8 ^N 2°6 ^: C:66.02, H:4.34, N:6.70. Found: C:65.93, H:4.40, N:6.6β.

Example 2

1,4-Bis (2-cyano-8-quinolinyloxy) butane was prepared by the method described in example 1 using 1,4-dibromobutane in place of 1, 3-propanediol ditosylate. Yield: 75%, m.p. 2 23333°°CC ⁽ (DDMMFF ⁾ ) .. AAnnaall.. CCaallcc.. ffoorr ^c C ₂₂ 4 ₄ ^H Hi ₁ 8 ₈ °02 _Λ ^N 4 ^: ; ' C:73.08, H:4.60, N.14.21. Found: C:72.92, H:4.59, N.14.17.

1 ,4-Bis (2-carboxy-8-quinolinyloxy) butane, m.p. 201-3 C (MeOH) (R 432) . Anal. Calc. for C ₂₄ H N 0 : C: 66.66, H: 4.66, N:6.48. Found: C:66.57., H:4.66, N:6.39.

Example 3

1,8-Bis (2-cyano-8-quinolinyloxy) octane was prepared by the method described in example 1 using 1,8-dibromooctane in place of 1, 3-propanediol ditosylate. Yield: 98%, m.p. 166- 1 16688..55°°CC ((CCHH ₃₃ CCNN)) .. AAnnaall.. Calc. for C _2g H _2g 0 N : C:74.64, H:5.82. Found: C:73.βl, H:5.76.

1, 8-Bis (2-carboxy-8-quinolinyloxy) octane (R 488) was obtai¬ ned by hydrolysis of the nitrile in 84% yield, m.p. 173-6°C (CH..C0OH, H ₂ 0) . Anal. Calc. for ^gH^N.O,: C: 68.84, H: 5.78 , N:5.74. Found: C-.68.41, H:5.82, :5.62.

Example 4

l,10-Bis(2-cyano-8-quinolinyloxy)decane was prepared by the method described in example 1 using 1,10-decanediol ditosy- late (E.J.P. Fear, J. Thrower and J. Veitch, J. Che . Soc. (1958) 1325) in place of 1,3-propanediol ditosylate. Yield: 59%, m.p. 150-5°C (toluene). Anal. Calc. for C ₃₀ H, ₀ N>O ₂ : C:75.29, H:6.32, N.11.71. Found: C:75.3, H:6.3, N:11.6.

1,10-Bis(2-carboxy-8-quinolinyloxy)decane (R 516) was obtai¬ ned by hydrolysis of the nitrile with KOH in glycol at 135- 140°C for 15 h. Yield: 72%, m.p. 172-8°C (CH ₃ COOH-H ₂ 0 and CHC1 ₃ ) . Methyl ester: M.p. 114-5°C. Anal. Calc. for C -,£-.HJ,o-N. _,0 _C b: C:70.57, H:6.66, N:5.14. Found: C: 70.50, H:6.62, N:5.09.

Example 5

1,5-Bis(2-cyano-8-quinolinyloxy)-3-oxapentane was obtained by the method described in example 1 using diethyleneglycol ditosylate (J. Dale and P.O. Kristansen, Acta Chem. Scand.

26 (1972) 1471) in place of 1,3-propanediol ditosylate.

Yield: 60%, m.p. 192-4°C (acetone). Anal. Calc. for

^C 24 ^H 18 ^N 4°3 ^{: C:70} - ²³ ' H:4.42, N:13.65. Found: C:70.6, H:4.5, N:13.6.

1,5-Bis(2-carboxy-8-quinolinyloxy)-3-oxapentane (R 448) was obtained by hydrolysis of the nitrile with Claisen's alkali at 80°C for 1 week. Yield: 38%, m.p. 170-2°C (EtOH and ben- zene).Anal. Calc. for C ₂₄ H ₂ N 0 : C:64.3, H:4.5, N:6.3. Found: C:64.0, H:4.5, N:6.2.

Example 6

1,8-Bis (2-cyano-8-quinolinyloxy)-3,6-dioxaoctane was obtai¬ ned by the method described in example 1 using triethylene- glycol ditosylate in place of 1,3-propanediol ditosylate. Yield: 60%, m.p. 143-6°C (toluene). Anal. Calc. for

C^H^N.O _. .: C:68.7, H:4.9, N:12.3, 0:14.1. Found: C:68.5, 26 22 4 4

H:4.9, N:12.3, 0: 13.9.

l,8-Bis(2-carboxy-8-quinolinyloxy)-3, 6-dioxaoctane (R 492) was obtained by hydrolysis of the nitrile with Claisen's alkali: H ₂ 0 2:1 at 80°C for 27 h. Yield: 70%, m.p. 148-9°C (EtOH) . Anal. Calc. for ^C ₂ 6 ^H 24 ^N 2°8 ^{: C:β3} - ⁴ ' H:4.9, N ^: 5.7, 0:26.0. Found: C:63.4, H:4.9, N:5.6, 0:26.2.

Example 7

1,11-Bis (2-cyano-8-quinolinyloxy)-3,6,9-trioxaundecane was obtained by the method described in example 1 using tetra- ethyleneglycol ditosylate in place of 1,3-propanediol dito- sylate. Yield: 68%, m.p. 137-140°C (toluene). Anal. Calc. for C _,_0 _o H-.O,N4,0D-: C:67.5, H:5.3, N:11.2. Found: C: 68.0, H:5.3,

N:ll.l.

1,11-Bis (2-carboxy-8-quinolinyloxy)-3,6,9-trioxaundecane (R 536) was obtained by hydrolysis of the nitrile with KOH in EtOH:H 0 1:1 at 80°C during 66 h. Yield: 87%, m.p. 132-

5°C ⁽ benzene ⁾ . Anal. Calc. for ^C 2 ₈ ^H 28 ^N 2° ₉ ^{: C:β2} - ⁷ ' H:5.3, N:5.2. Found: C:62.7, H:5.3, N:5.2.

Example 8

1,8-Bis(2-cyano-8-quinolinyloxy)-3,6-dioxa-4- (1-decyl)octa¬ ne was obtained by the method described in example 1 using 1,2-bis(2-hydroxyethoxy)dodecane ditosylate (M.Cinquini and P. Tundo, Synthesis (1976) 516) in place of 1,3-propanediol ditosylate. Yield: 80% (oil) .

1,8-Bis(2-carboxy-8-quinolinyloxy)-3,6-dioxa-4- (1-decyl) - octane (R 632) was obtained by hydrolysis of the nitrile with KOH in glycol for 10 days at 130°C. Yield: 41%, m.p. 93-7°C (EtOH) .

Example 9

l,8-[2-Cyano-7-(3- (5,5,7,7-tetramethyl-l-octenyl) )-8-quino- linyloxy]octane was prepared from 7-C3-(5,5,7,7-tetramethyl- 1-octenyl) ]-8-hydroxyquinoline-2-carbonitrile (SE patent application 8206378-5) (19.09 g, 56.7 mmol), 1,8-dibromooc- tane (8.02 g, 29.5 mmol) and K CO. (8.15 g, 59 mmol) in DMF (75 ml) at 75°C during 18 h. The product was isolated by toluene extraction and purified by chromatagraphy on silica gel with toluene: ethyl acetate 60:1 as eluant. Yield:

19.95 g (90%). Anal. Calc. for C ₅₂ H _{7Q 4} 0 ₂ : C:79.75, H:9.01, N:7.15. Found: C:79.65, H.-8.99, N:7.03.

The dinitrile (19.8 g, 25.3 mmol) was hydrolyzed with KOH (25 g) in ethanol (255 ml) at reflux during 17 h. Acidifi¬ cation and ether extraction yielded 19.8 g l,8-[2-carboxy- 7-(3-(5,5,7,7-tetramethyl-l-octenyl) )-8-quinolinyloxy]octane (R 821) (95% yield), m.p. 85-7°C. Mai. Calc. for C ₅₂ H _?2 N ₂ 06:

C-76.06, H:8.84, N:3.41. Found: C-.76.06, H:8.81, N:3.30.

Example 10

7-C3-(5,5,7,7-Tetramethyl-l-octenyl) ]-8-hydroxyquinoline- 2-carbonitrile (SE patent application 8206378-5) (1.02 g, 3.0 mmol) and K ₂ ^C0 3 (0.41 g, 3.0 mmol) in DMF (4.5 ml) were allowed to react with diethyleneglycol ditosylate (0.62 g, 1.5 mmol) during 4 h at 75°C. The product was worked up by ether extraction and purified by chromatography on silica gel, eluting with 0.5% EtOH in CH ₂ C1 ₂ to give 0.93 g 1,5- bis[2-cyano-7-(3- (5,5,7,7-tetramethyl-l-octenyl) )quinolinyl- oxyl-3-oxapentane (83% yield) , m.p. 91-6 C.

The dinitrile (0.83 g, 1.12 mmol) was hydrolyzed with KOH (1.2 g) in ethanol (17 ml) for 20 h at 75-80°C. The resul- ting diacid was isolated by ether extraction after acidifi¬ cation. Yield: 0.83 g of l,5-bis[2-carboxy-7- (3- (5,5,7,7- tetramethyl-1-octenyl) )quinolinyloxy]-3-oxapentane (R 81) , (95%), m.p. U5-120°C (cyclohexane) . Anal. Calc. for

C:73.82, H:8.26, N:3.59. Found: C: 73.82, H:8.24

^C 48 ^H 64 ^N 2°7 ^; N:3.56.

Example 11

1,11-Bis[2-cyano-7-{3- (5 ,5,7 ,7-tetramethyl-l-octeny1) )-8- quinolinyloxy]-3,6, -trioxaundecane was prepared by the method described in example 10 using tetraethyleneglycol ditosylate in place of diethyleneglycol ditosylate. Yield: 77%.

Hydrolysis with 10% KOH in EtOH gave 1,ll-bis[2-carboxy-7- (3-(5,5,7,7-tetramethyl-l-octenyl) )-8-quinolinyloxy]-3,6,9- triαxaundecane (R 869) in 90% yield.

Example 12

1,3-Bis(2-σarbethoxy-4-hydroxy-8-quinolinyloxy)propane was prepared by the Conrad-Limpach-Knorr reaction(B. Riegel, C.J. Albisetti, G.R. Lappin and R.H. Baker, J. Amer. Chem. Soc. _68_ (1946) 2685 and G.F. Lisk and G.W. Stacy, J. Amer. Chem. Soc. _68 (1946) 2686). K ₂ C0 ₃ (5.52 g, 40 mmol) was ad¬ ded to 2-nitrophenol (5.56 g, 40 mmol) in DMF (20 ml) , 1,3- dibromopropane was added and the reaction mixture kept at 70 C. The reaction mixture was cooled and poured into water and recrystallized from ethanol to give 4.80 g (75% yield) of 1,3-di(o-nitrophenoxy) ropane. This product was reduced with hydrazine (3 ml) and Pd(C) (0.2 g) in ethanol (150 ml) at reflux for 1.5 h. The resulting diamino compound was σon- verted to the hydrochloride. 1,3-Di(o-aminophenoxy)propane hydrochloride (4.38 g, 13 mmol) was stirred at ambient tem¬ perature for two days with diethyloxalacetic acid sodium salt (5.56 g, 26.5 mmol), anhydrous Na_S0. (5.8 g) and ab¬ solute alcohol(26 ml). Water was added and the product was extracted with ether. The ether phase was washed with 1M H SO., water and brine, yielding 6.60 g (85%) of the con¬ densation product. This product was dissolved xn diphenyl ether (15 ml) and -he. solution was added dropwise to β ^Λ ml ζfi ^~

( OMPI

refluxing diphenyl ether during 7 min. Reflux was conti¬ nued for an additional 8 min after which most of the sol¬ vent was distilled off at reduced pressure. Chromatography on silica gel with 5% EtOH in CH ₂ C1 ₂ and recrystallization from methanol yielded 1.44 g (14% yield based om 2-nitro- phenol) , m.p. 191-2°C.

The 4-hydroxy compound was alkylated (K ₂ C0 ₃ /DMF) with 1- chloro-5 _/ 5,7,7-tetramethyl-2-octane at 85°C overnight. The crude product was hydrolyzed with KOH-EtOH-H-O at reflux during 5 h. l,3-Bis[2-carboxy-4-(1-(5,5,7,7-tetramethyl-2- octenyloxy) ) -8-quinolinyloxy3propane (R 794) precipitated on addition of water and dilute H ₂ S0 ₄ to pH 3, 1.98 g (94% yield) , m.p. 167-9°C

Example 13

2-Nitrophenol (13.9 g, 0.10 mol) and Co (13.8 g, 0.10 mol) in DMF (50 ml) were stirred and heated to 85°C. Tri- ethyleneglycol ditosylate (22.9 g, 50 ml) in DMF (45 ml) was added and the reaction was left for 22.5 h at 85 C. The reaction mixture was worked up by addition of water and ex¬ traction with CH-C1-. The organic phase was washed with 10% NaHC0 ₃ - The product (7.84 g, 10 mmol) was dissolved in etha- nol (200 ml) and heated to reflux. Pd(C) (0.25 g) was added and then cautiously hydrazine (4 ml) . Refluxing was conti - nued for 2 h. Ethanol was removed by distillation and the product was converted to the hydrochloride (7.22 g, 89% yield). The hydrochloride (6.1 g, 15 mmol), diethyloxalace- tic acid sodium salt (6.3 g, 30 mmol) and anhydrous Na SO. (6.6 g) were stirred in absolute alcohol (30 ml) at room temp, for 20 h. Water was added and the product was isolated by ether extraction. The ether phase was washed with 1M H S0 ₄ , water and brine. Evaporation of the solvent yielded a yellow oil (8.06 g) . Diphenyl ether (7 ml) was added to the oil and the solution was added dropwise to refluxing di¬ phenyl ether (50 ml) during 4 min. Heating was continued for an additional 7 min, the solution was cooled and petroleum

OMH_

ether (75 ml b.p. 40-60°C) was added. The product, 1,8-bis- (2-carbethoxy-4-hydroxy-8-quinolinyloxy)-3,6-dioxaoctane, crystallized. Recrystallization from ethanol gave 2.87 g (33% yield), m.p. 141-2°C.

The 4-hydroxy compound (2.70 g, 4.66 mmol) was stirred at 60°C for 20 min with K CO (1.40 g, 10.2 mmol) in DMF (20 ml.). l-Chloro-5,5,7,7-tetramethyl-2-octene (2.13 g, 10.5 mmol) was added and the reaction was continued for 40 h at 60°C. Work-up by ether extraction and recrystallization from petroleum ether: ether 3:1 gave 3.20 g (75% yield) of the 4-alkoxy ester, m.p. 78-80°C.

This diethyl ester (3.10 g, 3.4 mmol) was hydrolyzed with KOH in ax_. ethanol at reflux for 1 h to give 1,8-bist2-car- boxy-4-(l-(5,5,7,7-tetramethyl-2-octenyloxy) ) -8-quinolinyl- oxy]-3,6-dioxaoctane (R 856) (2.29 g, 79%), m.p. 93-100°C (EtOH). Anal. Calc. for C ₅₀ H _{68 2} O ₁₍₎ .H ₂ O: C:68.6, H:8.06,

N:3.2. Found: C:68.8, H:8.0, N:3.2,

Example 14

The hydrochloride of 1,2-di(o-aminophenylthio) ethane (R.D. Cannon, B. Chiswell and L.M. Venanzi, J. Chem. Soc. A (1967) 1277) (3.25 g, 10 mmol) was stirred with diethyloxalacetic acid sodium salt (4.20 g, 20 mmol), Na_SO. (4.4 g) and ab¬ solute ethanol (20 ml) for two days yielding a partly crys¬ talline product after workup. This product was mixed with diphenyl ether (10 ml) and added dropwise to refluxing di- phenyl ether (70 ml) during 5 min. Reflux was continued for 10 min, the solution was cooled and petroleum ether (160 ml) was added. The precipitate formed was recrystallized from CHC1 ₃ - toluene to give 1,2-di(2-carbethoxy-4-hydroxy-8- quinolinylthio) ethane, m.p. 226-8°C (26% yield) .

1,2-Di(o-aminophenylthio) ethane (0.91 g, 3.3 mmol) and di¬ methyl acetylene dicarboxylate (0.95 ml, 7.0 mmol) were refluxed in methanol (30 ml for one day. The solvent was

OMPI

evaporated and the residue was dissolved in ether-CH^l- and washed with 2M HCl. Recrystallization from methanol afforded the anilino butenedioate (1.37 g, 74% yield), m.p. 119°C. This product was cyclized in refluxing diphenyl ether as de- scribed above, to yield l,2-di(2-carbomethoxy-4-hydroxy-8- quinolinylthio)ethane (1.07 g, 87% yield), m.p. 238-240°C.

The methyl or ethyl ester (2.13 mmol) and ₂ CO-. (0.65 g, 4.7 mmol) was stirred in DMF (15 ml) at 70°C for 15 min. l-Chloro-5,5,7,7-tetramethyl-2-octene (1.03 g, 5.11 mmol) was added and stirring was continued for 20 h. The mixture was cooled and poured into water. The product was filtered off and recrystallized from petroleum ether (b.p. 100-125 c) . Ethyl ester: yield 83% (1.51 g) , m.p. 127-145°C.

The diester (1.76 mmol) was hydrolyzed with KOH (1 g) , EtOH (20 ml) and H_0 (4 ml) at reflux overnight. Addition of wa¬ ter and acidification gave 1.09 g 1,2-di[2-carboxy-4-(1- (5,5,7,7-tetramethyl-2-octenyloxy) )-8-quinolinylthio]ethane (R 800) (77% yield) , m.p. 166-8°C (ag. acetic acid) . Anal.

Calc. for C4.6 ,-H6 →0 →N _→ 2,06 _C S2 →..H_20: C:67.4, H:7.6, N:3.4. Found:

C:67.8, H:7.4, N:3.4.

Example 15

An aqueou parts of metal sulfates ) was prepared by dissolving the metal salts in dilute sulfuric acid. The me¬ tal concentrations were kept around 2 mM and the pH of the solution was adjusted to about 2. A 10 mM solution of the appropriate reagent in chloroform was prepared and the two phases were agitated until equilibrium was reached. The two phases were then separated by centrifugation and the dist¬ ribution of each metal between the two phases was determi¬ ned. The percentage of metal ions extracted is given below.

OMPI

R 821 2.0 2 6 13 11 10

R 488 1.8 98 11 0 3 1 R 794 1.9 100 45 5 0 0

R 856 1.9 100 16 3 2 2

R 800 1.9 100 41 8 2 3

R 632 1.9 91 5 3 1 -

Example 16

An aqueous sulfuric acid solution at pH 2 containing equal concentrations of metal sulfates (Cu 2+, Zn2+, Fe3+, Cd2+ and K ) was contacted with an equal volume of a chloroform solution of the appropriate ligand until equilibrium was reached. The two phases were separated and the distribution of each metal between the two phases was determined. The percentage of metal ions extracted from the water is given below.

Reagent ? ^H eq Cu ²⁺ Zn ²⁺ Fe ³⁺ Cd ²⁺ K ⁺

R 821 1.9 1 3 5 1 0

R 488 1.8 99 14 5 1 7

R 794 1.9 100 49 11 - -

R 856 1.9 100 14 3 - 0

R 800 1.8 100 38 4 61 0

R 632 2.0 92 6 3 6 -

Examp _le 17

Equal amounts of sulfate salts of metals (Cu ²⁺ , Zn ²⁺ , Ni ²⁺ ,

2+ 2+ Co and Cd ) were dissolved in dilute sulfuric acid at pH 4. This solution was equilibrated at 25°C with a chloro- form solution of the ligand concerned. The two phases were separated and the distribution of each metal between the two phases was determined. The percentage of metal ions ex¬ tracted from the water phase is given below.

Reagent p ²⁺ Zn ²⁺ i ²⁺ Co ²⁺ cd ²⁺

*H Cu eq

R 821 3.0 27 8 10 14 4

R 488 2.6 100 66 5 4 5

R 794 2.3 100 80 5 5 33

R 856 2.3 100 54 5 0 -

R 800 2.1 100 79 4 17 81

R 632 2.5 99 14 4 - 7

Example 18

A mixture of equal amounts of metal sulfates (Cu 2+, Zn2+, Fe 2+ and Cd2+ was dissolved in sulfuric acid at different pH. The solution was equilibrated with chloroform solutions of the ligands concerned and the distribution of metals in the two phases was determined. The results are given below

(p ^c Hi.n = initial p ^{i ■} H- ,' p-Heq = pH at equilibrium)

Reagent pH. xn p ^* -H Cu ²⁺ eq Zn ²⁺ Fe ²⁺ Cd ²⁺

R 418 2.5 2.5 99 28 0 5

R 418 4.0 2.8 99 63 0 12

R 432 1.9 1.7 90 7 0 5

R 432 3.3 2.1 95 33 0 37

R 632 2.0 10Q 23 3 8

R 632 4.0 100 33 4 13

R 781 2.0 1.9 32 1 0 1

R 781 3.9 2.6 89 6 0 6

Example 19

A mixture of equal amounts of metal sulfates (Co 2+, Ni2+,

2+ 3+ Zn and Cr ) was dissolved in sulfuric acid at different pH. This solution was equilibrated with chloroform solu- tions of the ligands concerned and the distribution of metals between the two phases was determined. The results are given below (FH _±n = initial pH, pH = pH at equilib¬ rium) .

R 418 2.5 2.5 0 0 29 0

R 418 4.0 2.8 0 0 52 0

R 432 1.9 1.9 0 0 3 0

R 432 3.4 2.1 0 0 76 0

R 781 2.0 2.0 1 2 2 0

R 781 4.0 3.6 3 2 6 0

Example 20

A mixture of equal amount of metal sulfates (Mg 2+, Mn2+, Na + and Zn2+) was dissolved in sulfuric acid at different pH. This solution was equilibrated with chloroform solu- tions of the appropriate ligands and the amount of metals extracted from the water phase (in %) was determined. The results are given below (pH. = initial pH, pH = pH at equilibrium) .

Reagent pH. Mmrg2+ M _ΛΛ n ² + Na ^{+ c} in ^P eq Zn ²⁺

R 418 2.5 2.5 0 0 0 21

R 418 4.0 3.1 0 0 0 76

R 432 1.9 1.8 3 3 0 5

R 432 3.9 2.3 8 7 0 78

R 781 2.0 2.0 0 0 0 2

R 781 4.0 3.9 0 0 0 18

Example 21

A series of sulfuric acid solutions of single metal sulfates at pH 2 were shaken with equal volumes of chloroform solu¬ tions of the appropriate extractant. The percentage of metal removed from the water phase is given below.

Reagent Zn2+ Fe2+ Cu2+ Ni . 2^ Fe2+

R 492 0 0 48

R 536 11 0

R 516 10 0

R 632 14 5 78

Example 22

A series of sulfuric acid solution of single metal sulfa¬ tes at pH 4 were shaken with equal volumes of chloroform solutions of the appropriate extractants. The percentage of metal removed from the water phase is given below.

Reagent Zn ²⁺ Cu ²⁺

R 492 35 56

R 536 44 75

R 516 44 0 88

R 632 30

Example 23

A series of single metal sulfate solutions were prepared and contacted with a chloroform solution of R 488. The equilib¬ rium pH value of the aqueous phase was adjusted to a given value. The amount of metal extracted at a given pH value was determined. The pH _5Q values (the pH value at which 50% of the metal is extracted) for each metal were calculated and are given below.

Metal

Cu ²⁺ 0.9

Zn ²⁺ 2.0

Fe ³⁺ 2.4

Example 24

A plastic film containing the selective reagent dissolved in chloroform was placed between two solutions so that any transport of ions would occur only through the membrane. The first solution (feed solution) contained the metal ions in acidic sulfate solution, while the second contai¬ ned only concentrated sulfuric acid. Efter some time the metal ions were transfered from the feed solution into the sulfuric acid solution.