3,5-diiodoaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 3,5-diiodonitrobenzene (10 g, 26.7 mmol) in anhydrous EtOH (100 mL) was added SnCl2.2H2O (30 g, 133.6 mmol). The reaction mixture was brought to boil and a solution of NaBH4 (508 mg, 13.4 mmol) in EtOH (50 mL) was added slowly then stirred at reflux for 1 h. After the reaction was cooled down to 0° C., the mixture was neutralized with a solution of 3M NaOH (200 mL). The aniline derivative was extracted with chloroform, dried over Na2SO4 and evaporated under reduced pressure to afford 6.4 g of 3,5-diiodoaniline 11(70%) as a white solid. HR-ES(+): calculated for C6H5I2N [M] 345.8584, found 345.8583. at reflux for 1 h The aniline derivative was extracted with chloroform dried over Na2SO4 evaporated under reduced pressure

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,5-Diiodoaniline was obtained by the procedure of M. Bérubé (M. Bérubé, et al. Synthesis of Simplified Hybrid Inhibitors of Type 1 17β-Hydroxysteroid Dehydrogenase via the Cross-Metathesis and the Sonogashira Coupling Reactions, Organic Lett. 6 (2004) 3127-3130). 5 g (14.5 mmol) of 3,5-diiodoaniline were stirred with the solution of 5 mL of concentrated hydrochloric acid and 5 mL of water. The mixture was cooled to about −10° C. and 5.5 mL of 20% aqueous solution of NaNO2 was added dropwise with continuous stirring. The suspension was allowed to stir for another 40 minutes. Next, the cooled solution of 10.8 g (47.9 mmol) of SnCl2. 2H2O in 11 mL of concentrated HCl was added dropwise at −10° C. to the suspension of diazocompound. The reaction mixture was kept −10° C. for one hour and at 5° C. overnight. The obtained precipitate of a double salt with tin chloride was filtered off and washed with water. The residue was resuspended in water and added concentrated aqueous solution of NaOH to alkaline medium. The 3,5-diiodophenylhydrazine was extracted with ether, the organic layer was washed in turn with aqueous NaOH, Na2S2O3 and water, and dried with CaCl2. Ether was evaporated to give 4.2 g of 3,5-diiodophenylhydrazine. 1H-NMR (200 MHz, DMSO-d6), δ, ppm: 7.10 (2H, d, 1.2 Hz, arom.), 6.92 (1H, d, 1.2 Hz, arom.), 5.51 (1H, s, NH), 4.12 (2H, broad s, NH2). The reaction mixture was kept −10° C. for one hour and at 5° C. overnight The obtained precipitate of a double salt with tin chloride was filtered off washed with water added concentrated aqueous solution of NaOH The 3,5-diiodophenylhydrazine was extracted with ether the organic layer was washed in turn with aqueous NaOH, Na2S2O3 and water dried with CaCl2 Ether was evaporated

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 3,5-Diiodoaniline [Dininno, F.; Guthikonda, R. N.; Schmitt, S. M. 1994 U.S. Pat. No. 5,292,879 A] (1 g, 2.90 mmol), 6-(2-Trimethylsilanyl-ethoxycarbonylamino)-hexanoic acid (1 g, 3.77 mmol) in DMF (12 ml) were added DIPEA (0.9 ml, 5.8 mmol) and HATU (1.65 g, 4.35 mmol). The mixture was stirred for overnight at room temperature. The reaction mixture was diluted with Et2O. To the mixture was added sat.NaHCO3 and then separated. The aqueous phase was extracted with Et2O (3×40 ml). The combined extraction were washed with 5% HCl (30 ml), H2O (50 ml), sat.NaHCO3 (30 ml), and Brine (30 ml), and finally dried over MgSO4, filtered and concentrated in vacuo. The crude was purified by silica gel column with (Hexane:EtOAc=6:4) to afford 21 (1 g, 59%) as a colorless powder. 1H NMR (300 MHz, (CD3)2SO): δ 0.09 (S, 9H), 0.84 (t, J=2.1 Hz, 2H), 1.34 (m, 2H), 1.40 (m, 2H), 1.50 (m, 2H), 2.41 (t, J=1.8 Hz, 2H), 2.47 (m, 2H), 2.89 (m, 2H), 4.01 (t, 2H), 6.92 (bt, 1H), 7.68 (m, 1H), 7.99 (m, 2H); 13C NMR (75 MHz, (CD3)2SO): δ −0.72, 18.0, 25.2, 26.4, 29.9, 36.9, 61.9, 96.4, 127.0, 139.0, 142.3, 156.9, 172.2; IR (film): 3326, 2853, 2361, 1687, 1541, 1450, 1249, 837 cm−1; MS: (ESI)) [M+Na]+ 624.9 To the mixture was added NaHCO3 and then separated The aqueous phase was extracted with Et2O (3×40 ml) The combined extraction were washed with 5% HCl (30 ml), H2O (50 ml) NaHCO3 (30 ml), and Brine (30 ml), and finally dried over MgSO4 filtered concentrated in vacuo The crude was purified by silica gel column with (Hexane:EtOAc=6:4)

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

Procedure: To the solution of 3,5-diiodoaniline (5.0 g, 0.01 mol) in anhydrous acetone (150 mL) was added benzoylisothiocyanate (2.81 g, 0.012 mol) and the reaction mixture was stirred at room temperature for 30 min. Acetone was distilled off and the crude residue was washed with hexane to obtain desired compound as a yellow solid (6.35 g, 91%). Acetone was distilled off the crude residue was washed with hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,3-diiodo-5-nitro-benzene (15.80 g, 0.042 mol) in ethanol (200 mL) was added SnCl2.2H2O (28.50 g, 0.13 mol) portion wise at room temperature. The reaction mixture was heated under reflux at 80° C. for 1.5 h. After cooling to room temperature, the solvent was evaporated under reduced pressure and the crude solid thus obtained was basified with 4N NaOH solution to pH 12. The mixture was extracted with ethyl acetate (×3) and the combined organic layer was washed with brine solution and dried over Na2SO4. The solvent was removed under reduced pressure, to give the desired compound as a yellow solid (11.0 g, 75%). The reaction mixture was heated After cooling to room temperature the solvent was evaporated under reduced pressure the crude solid thus obtained The mixture was extracted with ethyl acetate (×3) the combined organic layer was washed with brine solution dried over Na2SO4 The solvent was removed under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,3-diiodo-5-nitro-benzene (15.80 g, 0.042 mol) in ethanol (200 mL) was added SnCl2.2H2O (28.50 g, 0.13 mol) portion wise at room temperature. The reaction mixture was heated under reflux at 80° C. for 1.5 h. After cooling to room temperature, the solvent was evaporated under reduced pressure and the crude solid thus obtained was basified with 4N NaOH solution to pH 12. The mixture was extracted with ethyl acetate (×3) and the combined organic layer was washed with brine solution and dried over Na2SO4. The solvent was removed under reduced pressure, to give the desired compound as a yellow solid (11.0 g, 75%). The reaction mixture was heated After cooling to room temperature the solvent was evaporated under reduced pressure the crude solid thus obtained The mixture was extracted with ethyl acetate (×3) the combined organic layer was washed with brine solution dried over Na2SO4 The solvent was removed under reduced pressure

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

Procedure: 3,5-Diiodoaniline [Dininno, F.; Guthikonda, R. N.; Schmitt, S. M. 1994 U.S. Pat. No. 5,292,879 A] (1 g, 2.90 mmol), 6-(2-Trimethylsilanyl-ethoxycarbonylamino)-hexanoic acid (1 g, 3.77 mmol) in DMF (12 ml) were added DIPEA (0.9 ml, 5.8 mmol) and HATU (1.65 g, 4.35 mmol). The mixture was stirred for overnight at room temperature. The reaction mixture was diluted with Et2O. To the mixture was added sat.NaHCO3 and then separated. The aqueous phase was extracted with Et2O (3×40 ml). The combined extraction were washed with 5% HCl (30 ml), H2O (50 ml), sat.NaHCO3 (30 ml), and Brine (30 ml), and finally dried over MgSO4, filtered and concentrated in vacuo. The crude was purified by silica gel column with (Hexane:EtOAc=6:4) to afford 21 (1 g, 59%) as a colorless powder. 1H NMR (300 MHz,(CD3)2SO): δ 0.09 (S, 9H), 0.84 (t, J=2.1 Hz, 2H), 1.34 (m, 2H), 1.40 (m, 2H), 1.50 (m, 2H), 2.41 (t, J=1.8 Hz, 2H), 2.47 (m, 2H), 2.89 (m, 2H), 4.01 (t, 2H), 6.92 (bt,1H), 7.68 (m, 1H), 7.99 (m, 2H); 13C NMR (75 MHz, (CD3)2SO): 6-0.72, 18.0, 25.2, 26.4, 29.9, 36.9, 61.9, 96.4, 127.0, 139.0, 142.3, 156.9, 172.2; IR (film): 3326, 2853, 2361, 1687, 1541, 1450, 1249, 837 cm−1; MS:(ESI)) [M+Na]+ 624.9 To the mixture was added NaHCO3 and then separated The aqueous phase was extracted with Et2O (3×40 ml) The combined extraction were washed with 5% HCl (30 ml), H2O (50 ml) NaHCO3 (30 ml), and Brine (30 ml), and finally dried over MgSO4 filtered concentrated in vacuo The crude was purified by silica gel column with (Hexane:EtOAc=6:4)

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

Procedure: 3,5-Diiodoaniline [Dininno, F.; Guthikonda, R. N.; Schmitt, S. M. 1994 U.S. Pat. No. 5,292,879 A] (1 g, 2.90 mmol), 6-(2-Trimethylsilanyl-ethoxycarbonylamino)-hexanoic acid (1 g, 3.77 mmol) in DMF (12 ml) were added DIPEA (0.9 ml, 5.8 mmol) and HATU (1.65 g, 4.35 mmol). The mixture was stirred for overnight at room temperature. The reaction mixture was diluted with Et2O. To the mixture was added sat.NaHCO3 and then separated. The aqueous phase was extracted with Et2O (3×40 ml). The combined extraction were washed with 5% HCl (30 ml), H2O (50 ml), sat.NaHCO3 (30 ml), and Brine (30 ml), and finally dried over MgSO4, filtered and concentrated in vacuo. The crude was purified by silica gel column with (Hexane:EtOAc=6:4) to afford 21 (1 g, 59%) as a colorless powder. 1H NMR (300 MHz,(CD3)2SO): δ 0.09 (S, 9H), 0.84 (t, J=2.1 Hz, 2H), 1.34 (m, 2H), 1.40 (m, 2H), 1.50 (m, 2H), 2.41 (t, J=1.8 Hz, 2H), 2.47 (m, 2H), 2.89 (m, 2H), 4.01 (t, 2H), 6.92 (bt,1H), 7.68 (m, 1H), 7.99 (m, 2H); 13C NMR (75 MHz, (CD3)2SO): 6-0.72, 18.0, 25.2, 26.4, 29.9, 36.9, 61.9, 96.4, 127.0, 139.0, 142.3, 156.9, 172.2; IR (film): 3326, 2853, 2361, 1687, 1541, 1450, 1249, 837 cm−1; MS:(ESI)) [M+Na]+ 624.9 To the mixture was added NaHCO3 and then separated The aqueous phase was extracted with Et2O (3×40 ml) The combined extraction were washed with 5% HCl (30 ml), H2O (50 ml) NaHCO3 (30 ml), and Brine (30 ml), and finally dried over MgSO4 filtered concentrated in vacuo The crude was purified by silica gel column with (Hexane:EtOAc=6:4)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,5-Diiodoaniline was obtained by the procedure of M. Bérubé (M. Bérubé, et al. Synthesis of Simplified Hybrid Inhibitors of Type 1 17β-Hydroxysteroid Dehydrogenase via the Cross-Metathesis and the Sonogashira Coupling Reactions, Organic Lett. 6 (2004) 3127-3130). 5 g (14.5 mmol) of 3,5-diiodoaniline were stirred with the solution of 5 mL of concentrated hydrochloric acid and 5 mL of water. The mixture was cooled to about −10° C. and 5.5 mL of 20% aqueous solution of NaNO2 was added dropwise with continuous stirring. The suspension was allowed to stir for another 40 minutes. Next, the cooled solution of 10.8 g (47.9 mmol) of SnCl2.2H2O in 11 mL of concentrated HCl was added dropwise at −10° C. to the suspension of diazocompound. The reaction mixture was kept −10° C. for one hour and at 5° C. overnight. The obtained precipitate of a double salt with tin chloride was filtered off and washed with water. The residue was resuspended in water and added concentrated aqueous solution of NaOH to alkaline medium. The 3,5-diiodophenylhydrazine was extracted with ether, the organic layer was washed in turn with aqueous NaOH, Na2S2O3 and water, and dried with CaCl2. Ether was evaporated to give 4.2 g of 3,5-diiodophenylhydrazine. 1H-NMR (200 MHz, DMSO-d6), δ, ppm: 7.10 (2H, d, 1.2 Hz, arom.), 6.92 (1H, d, 1.2 Hz, arom.), 5.51 (1H, s, NH), 4.12 (2H, broad s, NH2). The reaction mixture was kept −10° C. for one hour and at 5° C. overnight The obtained precipitate of a double salt with tin chloride was filtered off washed with water added concentrated aqueous solution of NaOH The 3,5-diiodophenylhydrazine was extracted with ether the organic layer was washed in turn with aqueous NaOH, Na2S2O3 and water dried with CaCl2 Ether was evaporated