| 95% |
With hydrogenchloride; indium In water at 100℃; for 0.5h; |
|
| 95% |
With ammonium chloride; zinc In methanol; water at 0℃; for 0.25h; |
General procedure for the synthesis of 4a-h
General procedure: Zinc dust (10 mmol) was added portionwise to a stirred solution of 2-nitroanil-ine (1 mmol) in MeOH and saturated NH4Cl solution (4 ml,1:1) over 15min at 0 °C.After completion of the reaction as determined by thin-layerchromatography(TLC), the reaction mixture was filtered through celite,and the MeOH was removed under vacuo.Then the aqueous residue was extracted with Et2O. Next,the organic solvent was dried (Na2SO4) and concentrated.The crude product was purified by column chromatography over silicagel. |
| 90% |
With tin(ll) chloride In ethyl acetate at 80℃; for 3h; |
|
| 80.9% |
With tin(II) chloride dihdyrate In ethanol for 2h; Reflux; |
Procedure for the synthesis of N-benzylbenzene-1,2-diamine 6
The stirred solution of N-benzyl-2-nitroaniline (5) (2.0 g,0.00876 m) in ethanol (50 mL), SnCl2.2H2O was added and the reaction mixture was heated under reflux for 2 h. Thesolvent was evaporated under reduced pressure. The residuewas dissolved in saturated aqueous NaHCO3 solution(100 mL) and product extracted with hot ethyl acetate (5 ×50 mL). The combined organic extracts were washed withbrine (2 × 50 mL), dried over Na2SO4 and the solvent underreduced pressure to get desired product (6). Yield 1.4 g,80.9%; m. p. 123-125 °C; 1H NMR (400 MHz, DMSO-d6):δ 7.37 (d, 2H, J = 7.28 Hz, Ar-H), 7.30 (t, 2H, J = 7.68 Hz,Ar-H), 7.21 (t, 1H, J = 7.24 Hz, Ar-H), 6.60 (dd, 1H, J =1.84, 7.28 Hz, Ar-H), 6.47 (m, 2H, Ar-H), 6.38 (dd, 1H,J = 2.08, 7.24 Hz, Ar-H), 4.92 (br s, 1H, -N-H), 4.39 (br s,2H, -NH2), 4.29 (s, 2H, benzylic); 13C-NMR (100 MHz,DMSO-d6): δ 140.12 (C-1), 135.81 (C-5), 134.87 (C-2),128.04 (2C, C-3′ and C-), 127.09 (2C, C-2′ and C-6′),126.43 (C-1′), 117.89 (C-4′), 117.08 (C-3), 114.54 (C-4),110.40 (C-6), 47.19 (C, benzylic); FTIR (neat, cm-1) νmax:3331 (N-H), 3028 and 3052 (C-H, aromatic), 2844 (C-H,aliphatic); GC-MS (m/z) = 198 [M]+; anal. calcd. (%) forC13H14N2: C, 78.75; H, 7.12; N, 14.13. Found: C, 78.20; H,7.81; N, 14.13. |
| 52% |
With acetic acid; zinc In methanol at 20℃; for 24h; |
|
| 50% |
With iron In ethanol; acetic acid at 20 - 40℃; |
|
| 50% |
With iron In ethanol; acetic acid at 40℃; |
16.Two
Step Two: To a solution of 49 (0.79 g, 3.5 mmol) in ethanol (7.0 mL) and acetic acid (7.0 mL) at room temperature, Fe powder (2.44 g, 34.6 mmol) was added and the suspension was stirred vigorously at 40° C. until thin layer chromatography indicated complete consumption of 49. The mixture was filtered through Celite, washing with chloroform. The filtrate was diluted with saturated sodium bicarbonate and the chloroform layer was dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (4:1 increasing to 1:1 hexanes:ethyl acetate) to give compound 50 (0.35 g, 50%) |
|
With hydrogenchloride; tin(ll) chloride |
|
|
With potassium hydroxide; sodium dithionite |
|
|
With ammonia; hydrogen In methanol |
|
|
With hydrazine hydrate In methanol for 0.166667h; Heating; Yield given; |
|
|
With hydrazine In methanol at 20℃; for 0.75h; |
1
N-Benzyl-benzene-l,2-diamine[0272] To a solution of benzyl-(2-nitro-phenyl)-amine and RaNi (0.7 mmol) in MeOH (20 mL) was added hydrazine monohydrate (14.0 mmol) portion-wise over 30 min at ambient temperature. The reaction was stirred for an additional 15 min at ambient temperature and then filtered over celite. The filtrate was concentrated to dryness and reconstituted in EtOAc (50 mL). The organic solution was washed with H2O (1 x 50 mL) and brine (1 x 50 mL), and then it was dried over MgSO4 and concentrated to dryness to provide iV-benzyl-benzene- 1 ,2-diamine. |
|
With hydrogen In ethanol |
5 B: N-(Benzyl)-2-aminoaniline and N-benzyl-2-mercaptobenzimidazole
B: N-(Benzyl)-2-aminoaniline and N-benzyl-2-mercaptobenzimidazole Platinum oxide (0.38 g) was prereduced under 50 psi of hydrogen gas in ethanol (50 ml). N-Benzyl-2-nitroaniline, (1.0 g, 4.4 mmole) was added, and the solution was hydrogenated at 50 psi of hydrogen for 3 hours to produce a mixture containing N-benzyl-2-aminoaniline. |
|
With acetic acid; zinc In ethanol Reflux; |
|
|
With hydrogenchloride; indium In water at 100℃; for 1h; |
|
|
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 3h; |
4.1.2 Synthetic procedure for nitro reduction (1b)
General procedure: To a stirred solution of 1a (1.0 eq.) in MeOH was added 10% Pd/C (10% w/w). The reaction mixture was stirred for 3 h at room temperature under H2 environment. After the reaction was completed, the reaction mixture was filtered and then concentrated in vacuo. The crude product was purified by flash column chromatography (ethyl acetate/hexane) to give desired product 1b. |
|
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 3h; |
4.1.2. Synthetic procedure for nitro reduction (1b)
General procedure: To a stirred solution of 1a (1.0 eq.) in MeOH was added 10% Pd/C(10% w/w). The reaction mixture was stirred for 3 h at room temperature under H2 environment. After the reaction was completed, the reaction mixture was filtered and then concentrated in vacuo. The crude product was purified by flash column chromatography (ethyl acetate/hexane) to give desired product 1b. |
|
With acetic acid; zinc In methanol at 20℃; |
|
|
With iron; ammonium chloride In ethanol; water for 4h; Reflux; Inert atmosphere; Schlenk technique; |
|
|
With hydrogenchloride; zinc In water at 20℃; |
|
|
With iron; acetic acid at 20℃; for 2h; |
|
|
With iron; acetic acid In water; ethyl acetate for 6h; Reflux; |
1.2 General procedure for preparation of N-substituted-benzene-1,2-diamine(B2a-B2x)
General procedure: A mixture of N-substituted-2-nitroanilines(B1a-B1x) (50 mmol), iron powder (250 mmol), acetic acid (500 mmol),water (35 ml) and ethyl acetate (80 ml) was heated to reflux for 6h. After completion of the reaction as indicated by TLC, the mixture was filtered immediately. The organic layer of the filtrate was separated, washed with water, dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain diamines (B2a-B2x) as a brown solid. |
|
With ammonium chloride; zinc In methanol at 20℃; for 1h; |
|
| 8.3 g |
With iron; acetic acid In ethanol at 60℃; for 2h; |
3.1.12. Synthesis of N1-benzylbenzene-1,2-diamine (4f)
A solution of 1-fluoro-2-nitrobenzene (15.0 mL, 0.14 mol, 1.0 equiv.), benzylamine (17.0 mL, 0.15mol, 1.1 equiv.) and TEA (25.0 mL, 0.18 mol, 1.3 equiv.) in DMSO (10 mL) was stirred at 100 °C for 18 h. After cooling down, the obtained orange solution was poured into water and the reaction productwas extracted with ethyl acetate (3 × 100 mL). The organic phase was washed with brine (1 × 50 mL)and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave N-benzyl-2-nitroaniline as a red solid (29.0 g, 89.5% yield), which was used in the next step without furtherpurification. A slurry of N-benzyl-2-nitroaniline (10.0 g, 44.0 mmol, 1.0 equiv.) and iron powder (12.3g, 220.0 mmol, 5.0 equiv.) in a mixture of 95% ethanol (100 mL) and glacial acetic acid (50 mL) wasstirred at 60 °C for 2 h. The progress of reaction was monitored by TLC, when the reaction wascompleted, the excess of volatiles was evaporated under reduced pressure. The obtained residue wastreated with water, the pH was adjusted to ca. 8 using sodium hydroxide and the reaction productwas extracted with ethyl acetate (3 × 150 mL). The organic phase was washed with brine (1 × 50 mL)and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the resultingfiltrate was evaporated under reduced pressure, giving N1-benzylbenzene-1,2-diamine (4f) as abrown solid (8.3 g, 96% yield) used in the next step without further purification. M.p. 49.0-50.0 °C,R.f. = 0.33 (hexane:ethyl acetate 9:1 v/v). 1H NMR (500 MHz, CDCl3) δ 7.48-7.43 (m, 2H, HAr), 7.43-7.37 (m, 2H, HAr), 7.36-7.31 (m, 1H, HAr), 6.89-6.83 (m, 1H, HAr), 6.80-6.69 (m, 3H, HAr), 4.35 (s, 2H,CH2), 3.46 (bs, 3H, NH2 + NH); 13C NMR (125 MHz, CDCl3) δ 139.4, 137.7, 134.2, 128.7, 127.9, 127.3,120.8, 118.9, 116.6, 112.1, 48.7; HRMS (ESI): m/z [M + H]+ calcd for C13H15N2: 199.12298, found:199.12313; |
|
With acetic acid; zinc In methanol at 20℃; |
|
|
With iron; acetic acid In water; ethyl acetate for 6h; Reflux; |
|
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