| 99% |
In dichloromethane at 20℃; for 24h; |
3.3. General Procedures for the Preparation of CompoundsI-V
General procedure: To a solution of amines (1 equiv) in (10 mL) of CH2Cl2,was added the corresponding isothiocyanate or phenylisocyanate(1 equiv), and the resulting solution was stirred at roomtemperature until TLC indicated the reaction was complete(24 h for (thio)ureas) and (4h for ureas). The solvent wasremoved in vacuum. The crude product was purified by columnchromatography to afford (thio)ureas I-V. The pureproducts I-III and V were obtained by recrystallization fromCH2Cl2. Compound IV was purified by chromatography on acolumn of silica gel with AcOEt/Acetone (9:1). 3.3.1. N-phenyl -N'-(2-pyridynyl)thiourea (I)Colorless solid; 99% yield; mp 176-178°C IR (v, cm-1KBr): 3172 (NH), 3037 (C-H), 1594 (C=C), 1547 (NH),1188 (C=S). 1H NMR (400 MHz, CDCl3) δ: 13.70 (1H,broad, H-9), 9.17 (1H, broad, H-2), 8.23 (1H, dd, J=5.3, 1.1Hz, H-5), 7.67 (2H, dd, J=7.9, 2.3 Hz, H-11, 15), 7.63 (1H,d, J=8.1 Hz, H-7), 7.43 (2H, t, J=7.9 Hz, H-12, H-14), 7.27(1H, m, H-13), 7.00 (1H, ddd, J=7.3, 5.3, 0.8 Hz, H-6), 6.92(1H, d, J=8.1 Hz, H-8). 13C NMR (100 MHz, CDCl3) δ:178.7 (C=S), 153.1 (C-3), 145.6 (C-5), 139.0 (C-7), 138.6(C-10), 128.7 (C-12, 14), 126.3 (C-13), 124.9 (C-11, 15),118.2 (C-6), 112.4 (C-8). EI MS (70eV) m/z: [M-1]+ 228.17(10), 227.14 (56), 78.03 (100), 77.05 (20) [24]. |
| 98% |
In ethanol for 1h; Heating; |
|
| 98% |
With C64H52CaN6 In neat (no solvent) at 60℃; for 12h; Schlenk technique; Glovebox; Inert atmosphere; |
|
| 97% |
In <i>tert</i>-butyl alcohol for 4h; Reflux; |
Preparation of Thioureas 3a-z
General procedure: Method B; To a solution of isothiocyanate 1 (1.0 mmol) in tert-butanol (10 mL) was added the corresponding amine 2 (1.2 mmol), andthe mixture was refluxed until isothiocyanate was consumed(TLC). Then, the solvent was evaporated, 10 mL of CH2Cl2 was added and the same work up used in method A was followed. |
| 96% |
With 2-(2,4,5,7-tetrabromo-3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid; oxygen In water; dimethyl sulfoxide at 20℃; for 8h; Schlenk technique; Sealed tube; Irradiation; Green chemistry; |
|
| 96% |
In neat (no solvent) at 20℃; for 0.166667h; Schlenk technique; Green chemistry; |
|
| 95% |
In dichloromethane at 20℃; for 3h; |
4.1.1 1,3-Diphenylthiourea [35]
To a stirred solution of 60 phenylisothiocyanate (1.00mmol; 135mg) in 61 dichloromethane (0.5mL) at room temperature, was added dropwise a solution of 62 aniline (1.00mmol; 93mg) in dichloromethane (0.5mL). The reaction was followed by TLC (dichloromethane) and completed in 3h. The resulting suspension was filtered and washed with diethyl ether; Yield 95%; white crystals; mp 142-144°C (lit [59]. 140-142°C); IR υmax (cm-1) 3202, 3053, 1598, 1526, 1491, 1449, 1342, 1313, 1288, 1242, 1171, 1069, 1021, 1003, 933, 756, 694, 642, 629, 610; 1H NMR (400MHz, DMSO-d6) δ (ppm) 9.79 (s, 2H, 2×NH), 7.48 (d, J= 7.4Hz, 4H, 2′ and 6′-ArCH), 7.33 (t, J= 8.2 and 7.6Hz, 4H,3′ and 5′-ArCH), 7.12 (t, J= 7.4Hz, 2H, 4′-ArCH); 13C NMR (101MHz, DMSO-d6) δ (ppm) 179.63 (2-CS), 139.46 (1′-ArC), 128.45 (ArCH), 124.44 (4′-ArCH), 123.66 (ArCH). |
| 95% |
In dichloromethane at 20℃; for 3h; |
4.1.1. 1,3-Diphenylthiourea [13]
To a stirred solution of phenyl isothiocyanate (1 mmol;135 mg) in dichloromethane (0.5 mL) at room temperaturewas added dropwise a solution of aniline (1 mmol; 93 mg)in dichloromethane (0.5 mL). The reaction was followed bythin-layer chromatography (dichloromethane) andcompleted in 3 h. The product so formed in suspensionwasfiltered and washed with ethyl ether; 217 mg (95%); whitecrystals; mp 142e144 C (lit. [14], 140e142 C). 1H NMR(400 MHz, DMSO-d6) d (ppm) 9.79 (s, 2H), 7.48 (d,J 7.4 Hz, 4H), 7.33 (t, J 8.2 and 7.6 Hz, 4H), 7.12 (t,J 7.4 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) d (ppm)179.6, 139.5, 128.5, 124.4, 123.7. |
| 95% |
With [κ2-{(Ph2P-(=Se))}2NCH2(C5H4N)ZnCl2] In toluene at 25℃; Schlenk technique; Inert atmosphere; |
General Procedure for the Catalytic Addition of Amines with RNCO and RNCS.
General procedure: A solution of primary or secondary amine (0.276 mmol) in toluene (1.0 mL) was added drop wise into the reaction mixture of RNCO (0.276 mmol) or RNCS (0.276 mmol) and zinc complex [{Ph2P(Se)2N-CH2C5H4N}ZnCl2] 2 (0.0138 mmol) to a 25 mL dry Schlenk flask. The reaction mixture was stirred for 2 hours at room temperature. Solvent was evaporated under vacuo. White solid compound obtained in each case. The conversion of amines was calculated from isolated pure products. The products were identified by 1H NMR spectroscopy and MS analysis; the values were compared with previous literature. |
| 93% |
In dichloromethane at 20℃; for 24h; |
|
| 93% |
for 0.00833333h; Microwave irradiation; Neat (no solvent); |
|
| 92% |
In chlorobenzene at 70℃; for 2h; Sealed tube; |
|
| 92% |
In dichloromethane at 20℃; |
4.1.2. Synthesis of model compounds
General procedure: In a dry flask equipped with a stirring bar under nitrogen atmosphere,1 mmol of aniline or p-trifluoromethylaniline or o-toluidinewas dissolved in 12 mL of dry DCM. 1 mmol of theappropriate isothiocyanate was added dropwise to the correspondinganiline solution at room temperature. The reactionmixture was left to stir overnight and then was evaporated todryness. The thiourea products were purified by column chromatographyon a short column, using pentane/EtOAc as eluent. |
| 90% |
In ethyl acetate for 1h; Reflux; |
|
| 90% |
In tetrahydrofuran at 50℃; for 48h; |
|
| 89% |
In benzene for 0.5h; Ambient temperature; |
|
| 88% |
In tetrahydrofuran at 20℃; for 40h; Inert atmosphere; |
|
| 87% |
In benzene at 20 - 25℃; |
|
| 85% |
In dichloromethane at 20℃; for 16h; Inert atmosphere; |
|
| 84.4% |
With pyridine at 20℃; Inert atmosphere; |
|
| 84% |
In dichloromethane at 20℃; for 24h; |
1.1 Step 1: Preparation of 1,3-diphenylthiourea
Phenyl isothiocyanate (phenyl isothiocyanate, 1.0 mL, 1.1 mmol) and aniline (aniline, 1.6 mL, 1.3 mmol) were dissolved in dry DCM (dry dichloromethane, 10 mL) at room temperature, followed by reaction for 24 hours. After completion of the reaction, the solvent was removed and filtered with a solution (100 mL) in which chloroform and n-hexane were mixed in a volume ratio of 2:8 to obtain 1,3-diphenylthiourea as a white solid (2.1 g, yield, 84%). |
| 84% |
In dichloromethane at 20℃; for 24h; Inert atmosphere; |
Preparation of S-Benzyl-N,N'-diphenyl isothiouronium iodide catalyst(1c)
Phenyl isothiocyanate (40 mmol) was added to a solution of aniline (40 mmol) in dry dichloromethane at room temperature. The reaction mixture was stirred for 24 hr, filtered, then washed with dichloromethane and dried, to give a white solid1,3-diphenylthiourea (5.03 g, yield 84%). Then, 1,3-diphenylthiourea (4.4 mmol) was added to a solution of benzyl iodide (13.2 mmol) in drydichloromethaneat room temperature. The reaction mixture was then stirred for 24 hr. The reaction mixture was concentrated in vacuo. The residue was purified via flash chromatography (hexane:ethyl acetate = 8:2), to give a yellow solidS-benzyl-N,N'-diphenyl isothiouronium iodide(1.14 g, yield 58%).mp1C;1H NMR (300MHz, DMSO):δ7.207~7.387(m, 15H),δ 4.445(s. 2H); HR TOF-MS for C20H18N2S: calcd 318.1186(M+), found 318.1185(M+). |
| 82% |
In ethanol for 0.0833333h; Ambient temperature; |
|
| 82% |
In toluene |
|
| 75% |
With triethylamine In dichloromethane at 20℃; Cooling with ice; |
|
| 75% |
With sodium hydrogencarbonate; (1-bromoethyl)benzne In 1,2-dichloro-benzene at 120℃; for 24h; |
General procedure for 4a
General procedure: A clean washed boiling tube equipped with a magnetic stir bar was charged with aniline 1a (0.0930g, 1 mmol), phenyl isothiocyanates 2a (0.1350 g, 1 mmol), 0.5 mmol of NaHCO3 and dichloroethane (1mL), the above mixture was stirred for 24 h at 120 °C temperature. After completion of the reaction, the mixture was poured into 10 mL of NaHCO3 solution. The product was extracted with ethyl acetate (10 mL × 3) and dried with anhydrous Na2SO4. Removal of the solvent under reduced pressure, the left-out residue was purified through column chromatography using silica gel (20% EtOAc/hexane) to obtained (Z)-N,3-diphenylthiazolidin-2-imine 4a in 82 % yield (0.2082g). |
| 27% |
With triethylamine In dichloromethane |
|
|
In acetone Heating; |
|
|
In diethyl ether Yield given; |
|
|
In ethanol Ambient temperature; |
|
|
In dichloromethane for 2h; Ambient temperature; |
|
|
In acetic acid at 69.85℃; |
|
|
In N,N-dimethyl acetamide at 20℃; for 0.25h; ultrasound irradiation; |
|
|
In dichloromethane |
|
|
In acetone at 20℃; for 6h; |
|
|
In benzene at 20℃; for 3h; |
|
|
In benzene at 25℃; |
|
|
In dichloromethane for 120h; Inert atmosphere; |
|
|
In acetonitrile at 20℃; for 1h; |
|
|
In N,N-dimethyl-formamide at 20℃; for 0.333333h; |
|
|
In acetonitrile at 20℃; |
Synthesis of 2
General procedure: To the solution of phenylisothiocyante 5 (0.1 mol) in acetonitrile (10 mL), added corresponding amine 6 and the resulting mixture was allowed to stir for 3-4 h at room temperature. The reaction mixture was evaporated under reduced pressure and resulting solid was poured in to water. The compound was separated by using methylenechloride (50 mL) which was dried over Na2SO4. The organic layer was concentrated and the crude product was purified using column chromatography. 2k: Yield 94%; viscous solid; Rf= 0.45 (Ethyl acetate/hexane; 1:4), IR (neat): 3200, 3163, 1665, 1600, 1554, 1471, 1455 cm-1; 1H NMR (CDCl3): δ 1.1 (m, 12H, 2C(CH3)2)), 2.99 (m, 2H, 2(CH(CH3)2)), 6.00 (bs, 1H, NH), 7.13 (t, J = 8.0 Hz, 2H, Ar-H), 7.28 (t, J = 7.6 Hz, 1H, Ar-H), 7.52 (t, J = 8.0 Hz, 2H, Ar-H), 7.81 (bs, 1H, NH). HRMS calcd for C13H20N2S m/z 236.1347, found 236.1339. |
|
With 1-butyl-3-methylimidazolium Tetrafluoroborate at 20℃; for 0.333333h; |
|
|
In dimethyl sulfoxide at 80℃; for 0.166667h; Inert atmosphere; |
|
|
In neat (no solvent) at 90℃; |
|
|
In ethanol Reflux; |
|
|
In toluene at 24.84℃; |
|
| 82 %Spectr. |
With [(ImDippN)Th{N(SiMe3)2}3] In benzene-d6 at 80℃; for 12h; Glovebox; Sealed tube; |
|
|
In ethanol Reflux; |
|
|
In acetone at 60℃; Reflux; |
4. Synthesis of Ligands L1 - L4
General procedure: Ligands L1 - L4 were synthesized according to the previous reported method.5b p-Methoxyaniline acetone solution (12 mmol p-methoxyaniline in 20 mL acetone) was added dropwise to the solution of phenyl isothiocyanate (12 mmol) in acetone (20 mL). The reaction mixture was heated to 60 °C and refluxed for 2-3 hours and the reaction was monitored by TLC. After completion of the reaction, the resulting precipitate was collected by filtration and washed with water and ethanol to afford the pure L4. |
|
In methanol Reflux; |
|
|
In acetonitrile at 20℃; |
Thioureas were prepared according to the reported procedure
General procedure: To a solution of aniline (10 mmol) in CH3CN (10 mL) was added isothiocyanate (10mmol). The reation was then stirred until complete conversion of the starting material monitored by TLC. The solvent was removed under reduced pressure and the residue was recrystallized from EtOH to get the desired thioureas 1. |
|
Inert atmosphere; |
|
| 1.497 g |
In dichloromethane for 0.75h; Cooling with ice; |
1
Place aniline (11 mmol),Triethylamine (36.2 mmol) and tetrahydrofuran 10 mL were placed in the flask,Stir for 10 minutes in an ice bath.Carbon disulfide (11 mmol) was then added dropwise to the mixture over 30 minutes; after the addition was complete,The mixture was stirred at room temperature for a further 10 hours; then cooled on an ice bath.Slowly added TsCl (12.1 mmol),After stirring for another 1h,Phenyl isothiocyanate to give 0.965 g.Dissolve 0.965 g of phenyl isothiocyanate in methylene chloride.Under ice bath conditions,Add 0.665 grams of aniline,After stirring the reaction for 45 minutes, the reaction is complete.Filter; filter cake washed with methylene chloride several times,Dried N,N-diphenyl thiourea 1.497 g will be dried. 1.497 g of N,N-diphenylthiourea and methylene chloride are mixed in a round bottom flask.Then add 7 mmol of malonyl chloride,Heat to reflux for 1 hour,After the reaction is complete,Spin off the solvent,Then 1 ml of 1.0 M hydrochloric acid was added to quench the reaction.washing,dry,Column chromatography,A barbituric acid derivative was obtained.The barbituric acid derivative and ethanol were mixed in a flask.Stir well,Add excess furfural and 0.5 ml pyridine,Stir for 2-3 hours at room temperaturefilter,Column chromatography,The target product 1,3-diphenyl-5(2-furylmethylene)thiobarbituric acid (1,3-diphenyl-5-(2-furanmethylene)thiobupiva) was obtained. (Acid acid) (structure shown in Formula 4) 0.346 g. |
|
In dichloromethane at 20℃; |
|
|
In acetone at 20℃; |
2.2. General Procedure for the Synthesis of Compounds-1-14
General procedure: Phenyl isothiocyanate (3 mmol) and 3 mmol of anilineswere taken in 6 mL of acetone. The reaction mixture wasstirred at room temperature for 6-8 hours. Progress of thereaction was monitored by thin layer chromatography (0.2mm silica gel 60). After completion of the reaction, resultingsolid product was subjected to the column chromatography(16-063-02 mm, mesh 70-230) with Hex: EtOAc (8:2) forpurification [11]. |
|
In N,N-dimethyl-formamide at 20℃; for 5h; |
|
|
In ethanol at 20℃; |
|
|
In toluene for 1h; |
1.1(e) Example 1(e) Synthesis of N,N′ disubstituted thioureas
A solution of alkylamine (3.0 mmol) in toluene (2.5 mL) was added to a solution of alkyl or aryl isothiocyanate (3.0 mmol) in toluene (2.5 mL). The resulting liquid was pumped under vacuum while stirring for 60 minutes to remove toluene, producing a powder. To produce thiourea crystals suitable for X-ray crystallography, the powder was dissolved in 10 mL of diethyl ether or toluene and allowed to evaporate. For N,N′-diphenyl-thiourea, the volume of toluene was increased to 5 mL for each, resulting in 10 mL total. |
|
at 20℃; for 24h; |
|
|
With sodium hydroxide In water at 20℃; for 1h; |
|
|
In dichloromethane at 20℃; for 3h; |
|
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