* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Journal of the American Chemical Society, 1933, vol. 55, p. 319
[2] Journal of the American Chemical Society, 1934, vol. 56, p. 2456,2458
2
[ 6283-25-6 ]
[ 5131-60-2 ]
Yield
Reaction Conditions
Operation in experiment
95%
With 5%-palladium/activated carbon; hydrazine hydrate In methanol at 20℃; for 0.0833333 h;
General procedure: To a mixture ofhalogenated nitroarene (1 mmol), Pd/C(5percent), and MeOH (5mL) was added NH2NH2·H2O (10 mmol), and the resultingsolution was heated at 80 °C reflux condition for 5 min. Thenthe mixture was filtered and concentrated in vacuo. Thecrude material was purified by flash column
41%
With iron; ammonium chloride In water at 78℃; for 1 h;
Method 61; 4-Chlorobenzene- 1 ,3-diamine; To a solution of ammonium chloride (1.57g, 29mmol) in H2O (10ml) were added 2- chloro-5-nitroaniline (1.Og, 5.8mmol) and iron powder (1.62 g, 29 mmol). The solution was stirred at 78 °C for one hour then filtered at 50 °C. The filtrate was collected and the solvent was removed under reduced pressure. The residue was taken up in DCM and filtered. The filtrate was collected and the solvent was removed under reduced pressure affording 337 mg of the title compound (41 percent); m/z 143.
98 %Chromat.
With hydrazine hydrate In ethanol at 80℃; for 1 h; Inert atmosphere
General procedure: Hydrazine hydrate was chosen as the hydrogen donor for the low emission of pollutants. In a typical procedure, hydrazine hydrate (4 equiv) was added into the reactor which containing fresh prepared catalyst as described above. Then the reactor was put into a preheated oil bath with a stirring speed of 500 rpm, and the substrate (1 mmol)dissolved in 1 mL ethanol was added drop-wisely under argon. The reactions were monitored by TLC. After the reaction, the reaction mixture was vacuum filtered through a pad of silica on a glass-fritted funnel and an additional 15 mL of ethyl acetate (5 mL portions) was used to rinse the product from the silica, the filtrate was concentrated in vacuum and analyzed by GC. Products were purified by column chromatography and identified by 1H NMR and 13C NMR.
With tin(II) chloride dihdyrate In ethanol at 20℃;
A mixture of 1-chloro-2,4-dinitro-benzene (100 mg, 0.5 mmol) and SnCl2.2H2O (1.12 g, 5 mmol) in ethanol (2.5 mL) was stirred at room temperature overnight. Water was added and then the mixture was basified to pH 7-8 with saturated NaHCO3 solution. The solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to yield 4-chloro-benzene-1,3-diamine (D-1) (79 mg, quant.). HPLC ret. time 0.38 min, 10-99percent CH3CN, 5 min run; ESI-MS 143.1 m/z (MH+).
Reference：
[1] Patent: US2015/231142, 2015, A1, . Location in patent: Paragraph 0569
[2] Journal of the Chinese Chemical Society, 2003, vol. 50, # 2, p. 267 - 271
[3] Synlett, 2004, # 10, p. 1835 - 1837
[4] Tetrahedron Letters, 1985, vol. 26, # 50, p. 6233 - 6234
[5] Angewandte Chemie, 1981, vol. 93, # 5, p. 477 - 479
[6] Synthetic Communications, 1999, vol. 29, # 6, p. 1033 - 1036
[7] Journal of the Chemical Society, 1900, vol. 77, p. 1217
[8] Monatshefte fuer Chemie, 1900, vol. 21, p. 268
[9] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1879, vol. 11, p. 376;[10] Justus Liebigs Annalen der Chemie, 1879, vol. 197, p. 84
[11] RSC Advances, 2015, vol. 5, # 71, p. 57444 - 57452
[12] Chemistry - A European Journal, 2015, vol. 21, # 52, p. 19016 - 19027
[13] Green Chemistry, 2016, vol. 18, # 8, p. 2435 - 2442
[14] Applied Catalysis A: General, 2017, vol. 537, p. 50 - 58
4
[ 106-47-8 ]
[ 5131-60-2 ]
Yield
Reaction Conditions
Operation in experiment
61.6%
With sulfuric acid; hydroxylamine In water at 40℃; Electrolysis; Inert atmosphere
The amination p-anisidine and p-chloroaniline wasconducted at 40 °C under argon in a custom-madethree-electrode cell [1] which allowed working withboth liquid and solid electrodes. The electrolyses in 8–12 M H2SO4 were performed using a Metrohm AutolabPGSTAT 302N potentiostat/galvanostat (current density–2 mA/cm2) and a mercury cathode (11 cm2); a platinumcathode (8.2 cm2) was used in more acidic media.The catholyte (25 mL) contained an aqueous solution of sulfuric acid, 0.1 mol/L of Ti(IV), 0.2 mol/Lof NH2OH, and 0.2 mol/L of substrate (p-anisidine or p-chloroaniline).When the electrolysis was complete, the catholyte was diluted with water and neutralized by treatmentfirst with a saturated aqueous solution of sodium hydroxide (on cooling) and then with NaHCO3. The products were extracted into chloroform (p-anisidine) or benzene (p-chloroaniline) and quantified by GLCon a Khromatek-Kristall 5000.2 chromatograph equipped with a flame ionization detector [CP-Sil 8CB capillary column, 60 m × 0.25 mm × 0.25 μm; oventemperature 160 °C; carrier gas (helium) inlet pressure 200 kPa]. Qualitative analyses were also performed ona Chrom-5 chromatograph (flame ionization detector; glass column, 3.5 m × 3 mm; stationary phase XE-60 or OV-17).
Reference：
[1] Russian Journal of Organic Chemistry, 2015, vol. 51, # 3, p. 439 - 440[2] Zh. Org. Khim., 2015, vol. 51, # 3, p. 452 - 453,2
5
[ 13243-32-8 ]
[ 5131-60-2 ]
Reference：
[1] Synthesis, 2001, # 1, p. 81 - 84
6
[ 108-24-7 ]
[ 97-00-7 ]
[ 5131-60-2 ]
[ 51867-83-5 ]
[ 62595-00-0 ]
Reference：
[1] Journal of Chemical Research, 2004, # 9, p. 596 - 598
7
[ 635-22-3 ]
[ 5131-60-2 ]
Reference：
[1] RSC Advances, 2015, vol. 5, # 43, p. 34398 - 34414
[2] Catalysis Science and Technology, 2015, vol. 5, # 1, p. 286 - 295
[3] Catalysis Letters, 2014, vol. 144, # 3, p. 439 - 446
8
[ 97-00-7 ]
[ 5131-60-2 ]
Reference：
[1] Patent: US2011/98311, 2011, A1,
9
[ 97-00-7 ]
[ 635-22-3 ]
[ 5131-60-2 ]
[ 6283-25-6 ]
[ 108-45-2 ]
Reference：
[1] Journal of Catalysis, 2008, vol. 255, # 2, p. 335 - 342
10
[ 136833-36-8 ]
[ 5131-60-2 ]
Reference：
[1] Helvetica Chimica Acta, 1952, vol. 35, p. 1470,1473
11
[ 97-00-7 ]
[ 635-22-3 ]
[ 5131-60-2 ]
[ 6283-25-6 ]
[ 108-45-2 ]
Reference：
[1] Journal of Catalysis, 2008, vol. 255, # 2, p. 335 - 342
With tin(II) chloride dihdyrate; In ethanol; at 20℃;
A mixture of 1-chloro-2,4-dinitro-benzene (100 mg, 0.5 mmol) and SnCl2.2H2O (1.12 g, 5 mmol) in ethanol (2.5 mL) was stirred at room temperature overnight. Water was added and then the mixture was basified to pH 7-8 with saturated NaHCO3 solution. The solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to yield 4-chloro-benzene-1,3-diamine (D-1) (79 mg, quant.). HPLC ret. time 0.38 min, 10-99% CH3CN, 5 min run; ESI-MS 143.1 m/z (MH+).
With platinum on activated charcoal; In methanol; at 30℃; under 3750.38 Torr; for 1.5h;Autoclave;Catalytic behavior;
General procedure: PtL1/L2/C (25.0 mg, 1.282 mol of Pt) and the desired amountof substrate were placed in a Teflon-coated stainless steel auto-clave (80.0 mL), equipped with magnetic stirrer, temperature andpressure controller. The autoclave was then sealed and evacu-ated, followed by charging it with deaerated MeOH (10.0 mL)by suction. Afterwards, the autoclave was placed in an oil pathwhich was heated to 30.0C. Once the latter temperature wasreached, the autoclave was pressurized with hydrogen (5.0 bar) and stirred at 800 rpm. After the desired reaction time, the auto-clave was removed from the oil bath and cooled to 20.0C, followedby venting the excess hydrogen. The suspension was centrifugedand the catalytic solution separated from catalyst by decantationin air atmosphere. To the latter solutions n-dodecane (100.0 L,0.44 mmol) was added as external standard and analyzed by GC.Recycling experiments were conducted by using recovered PtL1/2,applying the above descript protocol. The Ptsurface-atom related TOF(h-1) values were calculated according to the following equation:mmol(converted substrate) × [mmol(Ptsurface) × h]-1.The mmolof Ptsurface(i.e. amount of Pt atoms exposed to the substrate)using 25.0 mg of catalyst for the hydrogenation reactions were0.7179 mol for PtL1and 0.7948 mol for PtL2and PtC,according to the percentage of Pt-atoms localized on the NPs? sur-face (i.e. 56% (PtL1) and 62% for PtL2/C), using a HRTEM-basedcalculation [35].
...he aromatic nucleus, for example alkyl groups and halogen atoms. ...1,4-phenylenediamine2,4-tolylenediamine2,4-diaminoanisole2,4-diaminochlorobenzene2,5-diaminoanisole1,2-phenylenediamine2,6-tolylenediamine1,4-diaminonaphthalene...
[4-({5-[2-(4-<i>tert</i>-butoxyoxalyl-phenoxy)-acetylamino]-2-chloro-phenylcarbamoyl}-methoxy)-phenyl]-oxo-acetic acid <i>tert</i>-butyl ester[ No CAS ]
With benzoyl chloride; triethylamine; In dichloromethane; at 0℃; for 16h;
benzoyl chloride (5.2 ml) was added to a stirred mixture of 2,4-diaminochlorobenzene (6.42 g), triethylamine (12.5 ml) and methylene chloride (100 ml) which had been cooled to 0°C. The mixture was allowed to warm to ambient temperature and was stirred for 16 hours.. The mixture was evaporated and the residue was triturated under a saturated aqueous sodium bicarbonate solution.. The resultant solid was isolated, washed in turn with water and isohexane and dried under vacuum at 55°C. There was thus obtained N-(3-amino-4-chlorophenyl)benzamide as a solid (10.38 g); NMR Spectrum: (DMSOd6) 5.32 (s, 2H), 6.9 (m, 1H), 7.1 (d, 1H), 7.37 (d, 1H), 7.52 (m, 3H), 7.9 (d, 2H), 10.05 (s, 1H).
206 g of N,N'-dicyclohexylcarbodiimide and 71 g of 2,4-diaminodichlorobenzene were mixed with 500 ml of toluene, and to this was added 3 g of aluminum chloride in several portions at room temperature. Upon completion of the heat generation, to this was added 1 liter of methanol and 20 g of activated carbon, and the mixture was stirred for 1 hour while the inner temperature was kept at 50 C. The reaction solution was filtered to remove solids, about 0.3 liters of methanol was distilled off under reduced pressure, and the residue was cooled until the inner temperature reached 10 C. The precipitated crystals were filtered and dried to obtain 183 g of crystals of the guanidine compound of Specific example (2)-4. Identification of the guanidine compound of Specific Example (2) -4 was conducted using 1H-NMR (solvent: DMSO-d6, 300 MHz). Data are shown below. 1H-NMR (delta, ppm): 0.98 to 1.30 (m, 20 H), 1.56 (m, 4 H), 1.63 (m, 8 H), 1.86 (m, 8 H), 3.39 (m, 4 H), 4.74 (m, 4 H), 6.05 (d, 1 H), 6.16 (dd, 1 H), 7.06 (d, 1 H)
15.0 ml of pyridine are added to a solution of 173.0 g (0.9 mol) of ETHYLBENZOYL acetate in 3.2 litres of xylene, and the mixture is heated to 130-135°C. At that temperature, 107.0 g (0.75 mol) of 4-chloro-1, 3-phenylenediamine are added in portions to the solution and the ethynol that is liberated is distilled off continuously. After 5 hours, the reddish-brown solution is cooled to 25°C and 14.3 g (75 mol) of p-toluenesulfonic acid are added thereto. The resulting green suspension is then boiled for 6 hours under reflux, the water of reaction being distilled off. The suspension, which is now yellow, is allowed to cool to room tempera- ture. Filtration is then carried out, the precipitate is washed with a total of 500 mi of ethanol in three portions, and the crude product is dried for 20 hours at 80°C under a laboratory vacuum. There are obtained 179 G (0. 66 mol, yield 88 percent of theory) of A beige-brown powder of formula which, after recrystallisation from acetic acid, is in the form of white crystals having a melting point of 327°C.
The N-(3-amino-4-chlorophenyl)-2-nitrobenzamide used as a starting material was prepared as follows: 2-Nitrobenzoyl chloride (4.64 ml) was added to a stirred mixture of 3-amino-4-chloroaniline (5 g), triethylamine (9.78 ml) and methylene chloride (300 ml) and the reaction mixture was stirred at ambient temperature for 16 hours. The mixture was partitioned between methylene chloride and a saturated aqueous sodium bicarbonate solution. The organic phase was evaporated and the residue was purified by column chromatography on silica to give the required starting material (3.02 g); NMR Spectrum: (DMSOd6) 5.38 (s, 2H), 6.74 (d, 1H), 7.11 (d, 1H), 7.27 (s, 1H), 7.7-7.75 (m, 2H), 7.84 (t, 1H), 8.1 (d, 1H), 10.5 (s, 1H); Mass Spectrum: M+H+292 and 294.
The N-(5-benzamido-2-chlorophenyl)-4-methoxy-2-nitrobenzamide used as a starting material was prepared as follows: Benzoyl chloride (5.2 ml) was added to a stirred mixture of 2,4-diaminochlorobenzene (6.42 g), triethylamine (12.5 ml) and methylene chloride (100 ml) which had been cooled to 0° C. The mixture was allowed to warm to ambient temperature and was stirred for 16 hours. The mixture was evaporated and the residue was triturated under a saturated aqueous sodium bicarbonate solution. The resultant solid was isolated, washed in turn with water and isohexane and dried under vacuum at 55° C. There was thus obtained N-(3-amino-4-chlorophenyl)benzamide as a solid (10.38 g); NMR Spectrum: (DMSOd6) 5.32 (s, 2H), 6.9 (m, 1H), 7.1 (d, 1H), 7.37 (d, 1H), 7.52 (m, 3H), 7.9 (d, 2H), 10.05 (s, 1H).
The N-(3-amino-4-chlorophenyl)benzamide used as a starting material was prepared as follows: Benzoyl chloride (5.2 ml) was added to a stirred mixture of 2,4-diaminochlorobenzene (6.42 g), triethylamine (12.5 ml) and methylene chloride (100 ml) which had been cooled to 0° C. The mixture was allowed to warm to ambient temperature and was stirred for 16 hours. The mixture was evaporated and the residue was triturated under a saturated aqueous sodium bicarbonate solution. The resultant solid was isolated, washed in turn with water and isohexane and dried under vacuum at 55° C. to yield the required compound (10.38 g); NMR 5.32 (s, 2H), 6.9 (m, 1H), 7.1 (d, 1H), 7.37 (d, 1H), 7.52 (m, 3H), 7.9 (d, 2H), 10.05 (s, 1H).
The N-(3-amino-4-chlorophenyl)-3-dimethylaminobenzamide used as a starting material was prepared as follows: A solution of 3-dimethylaminobenzoyl chloride hydrochloride (20 g) in methylene chloride (100 ml) was added dropwise over 2 hours to a solution of 4-chloro-3-aminoaniline (14.25 g) and triethylamine (38 ml) in methylene chloride (500 ml), and the reaction stirred at ambient temperature for 18 hours. The precipitated solid was collected to give the title compound (29.7 g, quantitative): NMR: 2.94 (s, 3H), 5.28 (s, 2H), 6.88 (m, 2H), 7.09 (d, 1H), 7.16 (m, 2H), 7.28 (dd, 1H), 7.33 (m, 1H), 9.91 (s, 1H); m/s 290, 292.
EXAMPLE 1 A room temperature solution of 1-chloro-2,4-diaminobenzene (1.43 g, 10 mmol), 1-hexadecanesulfonyl chloride (3.24 g, 10 mmol), imidazole (0.68 g, 10 mmol) and toluene (20 mL) was stirred for 1 hr. Isopropyl alcohol (20 mL) was added and the reaction mixture was heated at 60° C. for 2 hours. Analysis by thin layer chromatography (tlc) (40percent ethyl acetate and 60percent heptane) indicated incomplete acylation and additional 1-hexadecanesulfonyl chloride (0.7 g, 2 mmol) was added and the reaction mixture was stirred at 60°-62° C. for an additional hour, at which time the reaction appeared to be complete by tlc analysis. The reaction solution was treated with hot water (50 mL) and the layers separated. The toluene layer was further washed twice with 50 mL of hot water. Heptane (20 mL) was added to the recovered toluene layer to precipitate the product, N-(3-amino-4-chlorophenyl)-1-hexadecanesulfonamide, which was isolated by cooling the mixture to about 0° C. and collecting the product by vacuum filtration. After being washed with cold heptane, the product was dried (yield=3.12 g, 72percent of the theoretical yield) and it melted at 103°-104° C. No impurities were observed by H1 NMR analysis.
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 25℃; for 10h;
Method 63; N-(3 - Amino-4-clilorophenyl)-3 -( 1 -cyano- 1 -methylethvDbenzamide; To a stirring solution of 3-(l-cyano-l-methylethyl)-benzoic acid (Method 73; 268 mg,1.41 mmol) in DMF (10 ml) were added 4-chlorobenzene-l,3-diamine (Method 61; 337 mg, 2.36 mmol), HATU (808 mg, 2.13 mmol) and DIEA (0.74 ml, 4.25 mmol) and the reaction mixture was stirred for 10 hours at 25 °C. The reaction mixture was partitioned between EtOAc and H2O. The organics were washed with H2O, brine and dried (MgSO4 (s)). The EPO <DP n="72"/>solvent was removed under reduced pressure affording 330 mg (98percent) of the title compound; m/z 314.
With 5%-palladium/activated carbon; hydrazine hydrate; In methanol; at 20℃; for 0.0833333h;
General procedure: To a mixture ofhalogenated nitroarene (1 mmol), Pd/C(5percent), and MeOH (5mL) was added NH2NH2·H2O (10 mmol), and the resultingsolution was heated at 80 °C reflux condition for 5 min. Thenthe mixture was filtered and concentrated in vacuo. Thecrude material was purified by flash column
41%
With iron; ammonium chloride; In water; at 78℃; for 1h;
Method 61; 4-Chlorobenzene- 1 ,3-diamine; To a solution of ammonium chloride (1.57g, 29mmol) in H2O (10ml) were added 2- chloro-5-nitroaniline (1.Og, 5.8mmol) and iron powder (1.62 g, 29 mmol). The solution was stirred at 78 °C for one hour then filtered at 50 °C. The filtrate was collected and the solvent was removed under reduced pressure. The residue was taken up in DCM and filtered. The filtrate was collected and the solvent was removed under reduced pressure affording 337 mg of the title compound (41 percent); m/z 143.
98%Chromat.
With hydrazine hydrate; In ethanol; at 80℃; for 1h;Inert atmosphere;
General procedure: Hydrazine hydrate was chosen as the hydrogen donor for the low emission of pollutants. In a typical procedure, hydrazine hydrate (4 equiv) was added into the reactor which containing fresh prepared catalyst as described above. Then the reactor was put into a preheated oil bath with a stirring speed of 500 rpm, and the substrate (1 mmol)dissolved in 1 mL ethanol was added drop-wisely under argon. The reactions were monitored by TLC. After the reaction, the reaction mixture was vacuum filtered through a pad of silica on a glass-fritted funnel and an additional 15 mL of ethyl acetate (5 mL portions) was used to rinse the product from the silica, the filtrate was concentrated in vacuum and analyzed by GC. Products were purified by column chromatography and identified by 1H NMR and 13C NMR.
1,2-diamino-4-chloro-5-thiocyanato-benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With bromine; acetic acid; In methanol;
EXAMPLE 4 To a solution of 14.2 g of 4(5)-chloro-o-phenylene diamine and 38 g of ammonium rhodanide in 120 ml of methyl alcohol 5 ml of acetic acid are added, whereafter a solution of 7.2 ml of bromine in 20 ml of methyl alcohol is added at a temperature of 15°-17° C. in 30-60 minutes. The mixture is diluted with water and after adjusting the pH value to 8, 1,2-diamino-4-chloro-5-thiocyanatobenzene is obtained, melting at 108°-110° C.
Pivaloyl chloride (2.71 mL, 22.0 mmol) was injected dropwise into a stirred solution of 4-chloro-1 ,3-benzenediamine (2.85 g, 20.0 mmol) in pyridine (20 mL) at room temperature. After stirring 60 h, water (200 mL) was added and the mixture extracted with ethyl acetate. The extracts were washed with 0.1 M aqueous hydrochloric acid, water and brine, dried (MgSO4) and evaporated under reduced pressure. The residue was recrystallised (toluene) to give the title compound (3.11 g, 69percent) as a solid. 1 H NMR (400MHz, DMSO-d6) delta 1.20 (s, 9H),5.26 (s, 2H), 6.77 (dd, J = 8.6, 2.5 Hz, 1 H), 7.06 (d, J = 8.6 Hz, 1 H), 7.22 (d, J = 2.5 Hz, 1H), 9.01 (s, 1H).
N-(3-amino-4-chlorophenyl)-2-methylpropanamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
69%
In dichloromethane; for 2h;
Lambda/-(3-Amino-4-chlorophenyl)-2-methylpropanamide. lsobutyric anhydride (2.33 ml_, 14.1 mmol) was injected into a stirred mixture of4-chloro-1 ,3-phenylenediamine (2.00 g, 14.0 mmol) and dichloromethane (30 ml_) and stirring continued for 2 h. Solvent was removed under reduced pressure until a precipitate had formed. The precipitate was filtered, washed with a little dichloromethane and dried to give the title compound (2.06 g, 69percent) as a purple-white powder. 1 H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.26 (d,J=6.82 Hz, 6 H) 2.49 (septet, J=6.86 Hz, 1 H) 4.09 (s, 2 H) 6.61 (dd, J=8.59, 2.53 Hz, 1 H) 7.12 (s, 1 H) 7.16 (d, J=8.59 Hz, 1 H) 7.38 (d, J=2.27 Hz, 1 H)
1,1-dimethylethyl {2-[(3-amino-4-chlorophenyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
33%
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; for 18h;
Benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (4.00 g, 7.69 mmol) was added to a mixture of 4-chloro-1 ,3-phenylenediamine (1.00 g, 7.01 mmol), N-(te/f-butoxycarbonyl)-2-aminoisobutyric acid (1.60 g, 7.87 mmol), N,N-diisopropylethylamine (3.00 mL, 17.2 mmol) and dichloromethane (7 ml_) and the mixture stirred 18 h under nitrogen. The mixture was diluted with ethyl acetate, washed with 1 M aqueous hydrochloric acid and brine, then dried (MgSO4). The solvent was removed under reduced pressure and the residue EPO <DP n="118"/>chromatographed (silica gel, 10-50percent ethyl acetate/hexane) to give the title compound (0.75 g, 33percent) as a solid. 1 H NMR (400 MHz, DMSO-c/6) delta ppm 1.36 (m, 15 H) 5.29 (s, 2 H) 6.73 (br s, 1 H) 6.88 (br s, 1 H) 7.05 (d, J=8.59 Hz, 1 H) 7.20 (s, 1 H) 9.21 (s, 1 H)
D-1; 4-Chloro-benzene-1,3-diamineA mixture of 1-chloro-2,4-dinitro-benzene (100 mg, 0.5 mmol) and SnCl2.2H2O (1.12 g, 5 mmol) in ethanol (2.5 mL) was stirred at room temperature overnight.Water was added and then the mixture was basified to pH 7-8 with saturated NaHCO3 solution.The solution was extracted with ethyl acetate.The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to yield 4-chloro-benzene-1,3-diamine (D-1) (79 mg, quant.). HPLC ret. time 0.38 min, 10-99percent CH3CN, 5 min run; ESI-MS 143.1 m/z (MH+)
With sulfuric acid; hydroxylamine; In water; at 40℃;Electrolysis; Inert atmosphere;
The amination p-anisidine and p-chloroaniline wasconducted at 40 °C under argon in a custom-madethree-electrode cell [1] which allowed working withboth liquid and solid electrodes. The electrolyses in 8?12 M H2SO4 were performed using a Metrohm AutolabPGSTAT 302N potentiostat/galvanostat (current density?2 mA/cm2) and a mercury cathode (11 cm2); a platinumcathode (8.2 cm2) was used in more acidic media.The catholyte (25 mL) contained an aqueous solution of sulfuric acid, 0.1 mol/L of Ti(IV), 0.2 mol/Lof NH2OH, and 0.2 mol/L of substrate (p-anisidine or p-chloroaniline).When the electrolysis was complete, the catholyte was diluted with water and neutralized by treatmentfirst with a saturated aqueous solution of sodium hydroxide (on cooling) and then with NaHCO3. The products were extracted into chloroform (p-anisidine) or benzene (p-chloroaniline) and quantified by GLCon a Khromatek-Kristall 5000.2 chromatograph equipped with a flame ionization detector [CP-Sil 8CB capillary column, 60 m × 0.25 mm × 0.25 mum; oventemperature 160 °C; carrier gas (helium) inlet pressure 200 kPa]. Qualitative analyses were also performed ona Chrom-5 chromatograph (flame ionization detector; glass column, 3.5 m × 3 mm; stationary phase XE-60 or OV-17).
(S)-tert-butyl {1-(2-chloro-6,7-dimethoxyquinazolin-4-yl)pyrrolidin-3-yl}carbamate[ No CAS ]
(S)-N1-{4-(3-aminopyrrolidin-1-yl)-6,7-dimethoxyquinazolin-2-yl}-4-chlorobenzene-1,3-diamine dihydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1.2 mg
Example 1 (S)-N1-{4-(3-aminopyrrolidin-1-yl)-6,7-dimethoxyquinazolin-2-yl}-4-chlorobenzene-1,3-diamine dihydrochloride A mixture of (S)-tert-butyl {1-(2-chloro-6,7-dimethoxy-quinazolin-4-yl)pyrrolidin-3-yl}carbamate (35 mg, 0.09 mmol) prepared in Reference Example 1, palladium acetate (1 mg, 5 mol percent), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthine (5.2 mg, 10 mol percent), cesium carbonate (59 mg, 0.18 mmol), 4-chloro-1,3-diaminobenzene (15.7 mg, 0.11 mmol) and 1,4-dioxane (1 ml) was stirred for 1 hour in a microwave (600 W). After cooling the reaction mixture to room temperature, the same was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1?dichloromethane/methanol=20/1). The resulting residue was dissolved in ethyl acetate, and then hydrochloric acid gas was added thereto. The resulting solid was filtered, washed, dried to prepare the titled compound (1.2mg) as a pale yellow solid.j0263] ?H-NMR (400 MHz, CD3OD) oe 7.62 (brs, 1H), 7.52 (brs, 1H), 7.15 (s, 1H), 6.90 (s, 1H), 6.86 (s, 1H), 4.41 (brs, 3H), 4.26 (brs, 2H), 3.98 (s, 3H), 3.90 (s, 3H), 2.66 (brs, 1H),2.35 (brs, 1H).
4-chloro-N1-(2'-iodo-6,6'-dimethyl-[1,1'-biphenyl]-2-yl)benzene-1,3-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With C50H46CuN6O4(1+)*F6P(1-); sodium carbonate; In dichloromethane; at 0℃; for 48h;Inert atmosphere; Schlenk technique;
General procedure: Under nitrogen atmosphere, a Schlenk tube was sequentially charged with cyclicdiaryliodonium salt (1.0 equiv), copper catalyst A1 or A2 (5.0 molpercent), Na2CO3 (3.0 equiv) anddichloromethane (0.05 M). After the mixture was chilled to proper temperature, the appropriateamine (1.2 equiv) was added and stirred for the time indicated in the experimental procedures.The reaction mixture was filtered through a plug of celite with ethyl acetate. The filtrate wasconcentrated under reduced pressure, and the residue was purified by column chromatographyon silica gel to deliver the corresponding product.
With potassium hydroxide; at 60℃; for 0.5h;Green chemistry;Catalytic behavior;
General procedure: In a round-bottomed flask equipped with mechanical stirrer,aryl halide (1 mmol), amine (1.2 mmol), catalyst (5 mg) and KOH(2 mmol) were stirred in ethanol (5 ml) under air atmosphere at 60C for 0.5 h. The progress of the reaction was monitored by TLC and GC. After completion of the reaction, CH2Cl2 (15 ml) was added and the catalyst was separated using an external magnet. The organic layer was washed with water (3 x 10 ml) and dried over anhydrous MgSO4. The product was isolated by column chromatography (nhexaneeethylacetate, 5:1) to afford the corresponding products.The products were characterized by their physical properties,melting points, and FT-IR, 1H NMR and 13C NMR [69-71].
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