nickel(2+);diacetate;tetrahydrate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The nickel hydroxide (line 50) is transferred to the nickel acetate production system tank (n) where it is dissolved in acetic acid (line 49, 1:1 ratio to dry nickel solids) and 100% wt acetic acid (line 51) are added to produce the final product nickel acetate tetrahydrate (line 52). The reaction is shown below: 2H2O+Ni(OH)2+2CH3COOH→Ni(CH3COO)2.4H2O

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 4 ml glass vial was added nickel acetate tetrahydrate (35 mg, 0.14 mmol), a Teflon stirbar, and distilled pyridine (1.4 ml). The vial was capped and the solution stirred vigorously to afford a blue solution. A solution of 2-nitro-N-(2-(pyridin-2-yl)phenyl)benzenesulfonamide (0.050 g, 0.14 mmol) in distilled pyridine (1.4 ml) was added to the reaction mixture dropwise. The resulting dark green-blue solution was stirred for 5 min, whereupon aqueous sodium hydroxide (2.55 M, 0.110 ml) was added dropwise. The mixture was sonicated briefly, leading to a yellow-green solution. Following 20 min, the solution was transferred to a 20 ml glass vial, and pentane (16 ml) was added dropwise with stirring, resulting in a biphasic system. The pentane layer was decanted, and ether (18 ml) was added. The mixture was stirred vigorously, leading to precipitation of a yellow solid. The mixture was centrifuged, the supernatant decanted, and the resulting residue was dried in vacuo. Minimal dicholoromethane was added to the residue, leading to the production of a quantity of orange solid. The mixture was filtered through Celite, affording a green solution that was concentrated in vacuo to afford the product 1x as a green solid (15.6 mg, 6%). An NMR sample was allowed to stand at ambient temperature for 2 days, during which time large green crystals grew. One of these crystals was analyzed by X-ray diffraction (see FIG. 5). a Teflon stirbar, and distilled pyridine (1.4 ml) The vial was capped to afford a blue solution was added dropwise The mixture was sonicated briefly was added dropwise with stirring resulting in a biphasic system The pentane layer was decanted ether (18 ml) was added The mixture was stirred vigorously leading to precipitation of a yellow solid the supernatant decanted, and the resulting residue was dried in vacuo Minimal dicholoromethane was added to the residue The mixture was filtered through Celite affording a green solution that was concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 4 ml glass vial was added nickel acetate tetrahydrate (35 mg, 0.14 mmol), a Teflon stirbar, and distilled pyridine (1.4 ml). The vial was capped and the solution stirred vigorously to afford a blue solution. A solution of 2-nitro-N-(2-(pyridin-2-yl)phenyl)benzenesulfonamide (0.050 g, 0.14 mmol) in distilled pyridine (1.4 ml) was added to the reaction mixture dropwise. The resulting dark green-blue solution was stirred for 5 min, whereupon aqueous sodium hydroxide (2.55 M, 0.110 ml) was added dropwise. The mixture was sonicated briefly, leading to a yellow-green solution. Following 20 min, the solution was transferred to a 20 ml glass vial, and pentane (16 ml) was added dropwise with stirring, resulting in a biphasic system. The pentane layer was decanted, and ether (18 ml) was added. The mixture was stirred vigorously, leading to precipitation of a yellow solid. The mixture was centrifuged, the supernatant decanted, and the resulting residue was dried in vacuo. Minimal dicholoromethane was added to the residue, leading to the production of a quantity of orange solid. The mixture was filtered through Celite, affording a green solution that was concentrated in vacuo to afford the product 1x as a green solid (15.6 mg, 6%). An NMR sample was allowed to stand at ambient temperature for 2 days, during which time large green crystals grew. One of these crystals was analyzed by X-ray diffraction (see FIG. 5). a Teflon stirbar, and distilled pyridine (1.4 ml) The vial was capped to afford a blue solution was added dropwise The mixture was sonicated briefly was added dropwise with stirring resulting in a biphasic system The pentane layer was decanted ether (18 ml) was added The mixture was stirred vigorously leading to precipitation of a yellow solid the supernatant decanted, and the resulting residue was dried in vacuo Minimal dicholoromethane was added to the residue The mixture was filtered through Celite affording a green solution that was concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add nickel (II) acetate tetrahydrate (24.8 gms. 10 mmol) to a stirred solution of kanamycin A (9.7 gms., 20 mmol) in dimethylsulfoxide (400 ml.). Stir at room temperature for 30 minutes, then to the resulting nickel (II) salt complex thereby formed add N-benzyloxycarbonyloxyphthalimide (13.0-15.6 gms., 44-52.6 mmol) in dimethylsulfoxide (70 ml.) over a 10 minute period. Stir at room temperature for one hour, then pour the reaction mixture into ether (2500 ml.) and shake one minute. Allow the oil to settle and decant the supernatant dimethylsulfoxide ether. Repeat this procedure two more times using 1500 ml. and 1000 ml., respectively, of ether. Dissolve the resultant gummy residue in methanol (1000 ml.) and concentrated ammonium hydroxide (50 ml.). Bubble hydrogen sulfide through the solution and separate the resultant precipitate of nickel (II) sulfide through a pad of Celite and wash the residue with methanol. Stir the combined filtrate and methanol wash with Amberlite IRA-401S (OH⃝) ion exchange resin (300 gms.), filter off the resin and evaporate the filtrate in vacuo. Triturate the resultant gummy residue with a 50:50 mixture of acetonitrile:ether and filter the resultant white solid to obtain 3,6'-di-N-benzyloxycarbonylkanamycin A; yield 12.5 gms. (83.5% theory); [α]D26 +78° (c, 4.84 in 50% aqueous methanol). Analysis Calculated for: C34H48O15N4.H2O; C, 56.2; H, 6.75; N, 6.94%. Found: C, 51.02; H, 6.26; N, 6.85%. E. Treat each of the following aminoglycosides with a mixture of cupric acetate hydrate and nickel (II) acetate tetrahydrate or with cobalt (II) acetate tetrahydrate or with cadmium (II) acetate dihydrate according to the procedures of Examples 11A through 11D, respectively.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The nickel hydroxide (line 144) is transferred to the nickel re-slurry tank 147 where water (line 145) and 100 wt % acetic acid (146) are added to produce the final product, nickel acetate tetrahydrate (line 148). The reaction is shown below 2H2O+Ni(OH)2+2CH3COOH→Ni(CH3COO)2.4H2O are added

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The nickel hydroxide (line 144) is transferred to the nickel re-slurry tank 147 where water (line 145) and 100 wt % acetic acid (146) are added to produce the final product, nickel acetate tetrahydrate (line 148). The reaction is shown below 2H2O+Ni(OH)2+2CH3COOH→Ni(CH3COO)2.4H2O are added

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add nickel (II) acetate tetrahydrate (24.8 gms., 10 mmol) to a stirred solution of kanamycin A (9.7 gms., 20 mmol) in dimethylsulfoxide (400 ml.). Stir at room temperature for 30 minutes, then to the resulting nickel (II) salt complex thereby formed add N-benzyloxycarbonyloxyphthalimide (13.0-15.6 gms., 44-52.6 mmol) in dimethylsulfoxide (70 ml.) over a 10 minute period. Stir at room temperature for one hour, then pour the reaction mixture into ether (2500 ml.) and shake one minute. Allow the oil to settle and decant the supernatant dimethylsulfoxide ether. Repeat this procedure two more times using 1500 ml. and 1000 ml., respectively, of ether. Dissolve the resultant gummy residue in methanol (1000 ml.) and concentrated ammonium hydroxide (50 ml.). Bubble hydrogen sulfide through the solution and separate the resultant precipitate of nickel (II) sulfide through a pad of Celite and wash the residue with methanol. Stir the combined filtrate and methanol wash with Amberlite IRA-401S (OH⃝) ion exchange resin (300 gms.), filter off the resin and evaporate the filtrate in vacuo. Triturate the resultant gummy residue with a 50:50 mixture of acetonitrile:ether and filter the resultant white solid to obtain 3,6'-di-N-benzyloxycarbonylkanamycin A; yield 12.5 gms. (83.5% theory); [α]D26 + 78° (c, 4.84 in 50% aqueous methanol). Analysis Calculated for: C34H48O15N4.H 2 O; C, 56.2; H, 6.75; N, 6.94%. Found: C, 51.02; H, 6.26; N, 6.85%.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add nickel (II) acetate tetrahydrate (24.8 gms., 10 mmol) to a stirred solution of kanamycin A (9.7 gms., 20 mmol) in dimethylsulfoxide (400 ml.). Stir at room temperature for 30 minutes, then to the resulting nickel (II) salt complex thereby formed add N-benzyloxycarbonyloxyphthalimide (13.0-15.6 gms., 44-52.6 mmol) in dimethylsulfoxide (70 ml.) over a 10 minute period. Stir at room temperature for one hour, then pour the reaction mixture into ether (2500 ml.) and shake one minute. Allow the oil to settle and decant the supernatant dimethylsulfoxide ether. Repeat this procedure two more times using 1500 ml. and 1000 ml., respectively, of ether. Dissolve the resultant gummy residue in methanol (1000 ml.) and concentrated ammonium hydroxide (50 ml.). Bubble hydrogen sulfide through the solution and separate the resultant precipitate of nickel (II) sulfide through a pad of Celite and wash the residue with methanol. Stir the combined filtrate and methanol wash with Amberlite IRA-401S (OH⃝) ion exchange resin (300 gms.), filter off the resin and evaporate the filtrate in vacuo. Triturate the resultant gummy residue with a 50:50 mixture of acetonitrile:ether and filter the resultant white solid to obtain 3,6'-di-N-benzyloxycarbonylkanamycin A; yield 12.5 gms. (83.5% theory); [α]D26 +78° (c, 4.84 in 50% aqueous methanol). Analysis Calculated for: C34H48O15N4.H2O; C, 56.2; H, 6.75; N, 6.94%. Found: C, 51.02; H, 6.26; N, 6.85%.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The nickel hydroxide (line 50) is transferred to the nickel acetate production system tank (n) where it is dissolved in acetic acid (line 49, 1:1 ratio to dry nickel solids) and 100% wt acetic acid (line 51) are added to produce the final product nickel acetate tetrahydrate (line 52). The reaction is shown below: 2H2O+Ni(OH)2+2CH3COOH→Ni(CH3COO)2.4H2O

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 4 ml glass vial was added nickel acetate tetrahydrate (35 mg, 0.14 mmol), a Teflon stirbar, and distilled pyridine (1.4 ml). The vial was capped and the solution stirred vigorously to afford a blue solution. A solution of 2-nitro-N-(2-(pyridin-2-yl)phenyl)benzenesulfonamide (0.050 g, 0.14 mmol) in distilled pyridine (1.4 ml) was added to the reaction mixture dropwise. The resulting dark green-blue solution was stirred for 5 min, whereupon aqueous sodium hydroxide (2.55 M, 0.110 ml) was added dropwise. The mixture was sonicated briefly, leading to a yellow-green solution. Following 20 min, the solution was transferred to a 20 ml glass vial, and pentane (16 ml) was added dropwise with stirring, resulting in a biphasic system. The pentane layer was decanted, and ether (18 ml) was added. The mixture was stirred vigorously, leading to precipitation of a yellow solid. The mixture was centrifuged, the supernatant decanted, and the resulting residue was dried in vacuo. Minimal dicholoromethane was added to the residue, leading to the production of a quantity of orange solid. The mixture was filtered through Celite, affording a green solution that was concentrated in vacuo to afford the product 1x as a green solid (15.6 mg, 6%). An NMR sample was allowed to stand at ambient temperature for 2 days, during which time large green crystals grew. One of these crystals was analyzed by X-ray diffraction (see FIG. 5). a Teflon stirbar, and distilled pyridine (1.4 ml) The vial was capped to afford a blue solution was added dropwise The mixture was sonicated briefly was added dropwise with stirring resulting in a biphasic system The pentane layer was decanted ether (18 ml) was added The mixture was stirred vigorously leading to precipitation of a yellow solid the supernatant decanted, and the resulting residue was dried in vacuo Minimal dicholoromethane was added to the residue The mixture was filtered through Celite affording a green solution that was concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add nickel (II) acetate tetrahydrate (24.8 gms. 10 mmol) to a stirred solution of kanamycin A (9.7 gms., 20 mmol) in dimethylsulfoxide (400 ml.). Stir at room temperature for 30 minutes, then to the resulting nickel (II) salt complex thereby formed add N-benzyloxycarbonyloxyphthalimide (13.0-15.6 gms., 44-52.6 mmol) in dimethylsulfoxide (70 ml.) over a 10 minute period. Stir at room temperature for one hour, then pour the reaction mixture into ether (2500 ml.) and shake one minute. Allow the oil to settle and decant the supernatant dimethylsulfoxide ether. Repeat this procedure two more times using 1500 ml. and 1000 ml., respectively, of ether. Dissolve the resultant gummy residue in methanol (1000 ml.) and concentrated ammonium hydroxide (50 ml.). Bubble hydrogen sulfide through the solution and separate the resultant precipitate of nickel (II) sulfide through a pad of Celite and wash the residue with methanol. Stir the combined filtrate and methanol wash with Amberlite IRA-401S (OH⃝) ion exchange resin (300 gms.), filter off the resin and evaporate the filtrate in vacuo. Triturate the resultant gummy residue with a 50:50 mixture of acetonitrile:ether and filter the resultant white solid to obtain 3,6'-di-N-benzyloxycarbonylkanamycin A; yield 12.5 gms. (83.5% theory); [α]D26 +78° (c, 4.84 in 50% aqueous methanol). Analysis Calculated for: C34H48O15N4.H2O; C, 56.2; H, 6.75; N, 6.94%. Found: C, 51.02; H, 6.26; N, 6.85%. E. Treat each of the following aminoglycosides with a mixture of cupric acetate hydrate and nickel (II) acetate tetrahydrate or with cobalt (II) acetate tetrahydrate or with cadmium (II) acetate dihydrate according to the procedures of Examples 11A through 11D, respectively.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The nickel hydroxide (line 144) is transferred to the nickel re-slurry tank 147 where water (line 145) and 100 wt % acetic acid (146) are added to produce the final product, nickel acetate tetrahydrate (line 148). The reaction is shown below 2H2O+Ni(OH)2+2CH3COOH→Ni(CH3COO)2.4H2O are added