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CAS No. : | 1205-64-7 | MDL No. : | MFCD00008530 |
Formula : | C13H13N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | TWPMMLHBHPYSMT-UHFFFAOYSA-N |
M.W : | 183.25 | Pubchem ID : | 14569 |
Synonyms : |
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.08 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 60.95 |
TPSA : | 12.03 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | Yes |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.76 cm/s |
Log Po/w (iLOGP) : | 2.48 |
Log Po/w (XLOGP3) : | 3.75 |
Log Po/w (WLOGP) : | 3.74 |
Log Po/w (MLOGP) : | 3.61 |
Log Po/w (SILICOS-IT) : | 3.24 |
Consensus Log Po/w : | 3.36 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.84 |
Solubility : | 0.0264 mg/ml ; 0.000144 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.7 |
Solubility : | 0.037 mg/ml ; 0.000202 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.35 |
Solubility : | 0.000813 mg/ml ; 0.00000444 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 1.56 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.2% | With sodium t-butanolate In toluene at 20 - 130℃; Inert atmosphere | 3.0 g (30 mmol) of sodium tert-butoxide, 217 mg (0.5 mmol) of IPr-HCl (compound No. 1), 45 mg (0.2 mmol) of palladium(II) acetate, 3.67 g (20 mmol) of 3-methyldiphenylamine, 3.2 g (10 mmol) of 4,4'-dibromobiphenyl and 30 ml of toluene were put into a 50-ml three-neck flask equipped with a stirrer, a condenser tube, a thermometer and a gas-introducing duct, in an argon current at room temperature, and reacted under reflux in an oil bath controlled at a temperature of 130°C for 7 hours. The reaction liquid was cooled to room temperature, then left overnight at room temperature, and 150 ml of methylene chloride was added thereto. The insoluble matter was removed by filtration, and the filtrate was washed twice with 50 ml of water. This was dewatered and dried with 30 g of anhydrous sodium sulfate, and the solvent was evaporated away to give a residue. The residue was purified through column chromatography (carrier, Fuji Silicia's NH silica gel 150 g; eluent, cyclohexane) to give 4.4 g of N,N'-diphenyl-N,N'-di(m-tolyl)benzidine (TPD) (yield 85.2percent). |
51% | Stage #1: With sodium hydride; magnesium bromide In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 2 h; Inert atmosphere Stage #2: With iron(II) chloride In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 14 h; Inert atmosphere |
In a 100 ml flask purged with a nitrogen atmosphere,30 g of xylene, 7.33 g (40 mmol) of N- (3-methylphenyl) aniline, 0.96 g (40 mmol) of sodium hydride,7.36 g (40 mmol) of magnesium bromide was charged,The reaction solution was heated to 140 ° C. while stirring.After aging for 2 hours at the same temperature, 0.063 g (0.5 mmol) of iron (II) chloride,3.12 g (10 mmol) of 4,4'-dibromobiphenyl was added,Further aging was carried out for 14 hours at the same temperature. After completion of the reaction,After cooling, water was added to dissolve the salt and liquid separation was carried out. After separating the organic layer,As a result of analysis by GC using the internal standard method,Bis (3-methylphenylphenylamino) biphenyl as a target product was produced in a yield of 51percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.3% | With bis-triphenylphosphine-palladium(II) chloride; sodium hydroxide; at 230℃; for 8h;Inert atmosphere; Dean-Stark; | M-toluidine as an amine compound, bromobenzene as a halogenated allyl compound, bisphosphoryl phosphine dicycloride as a catalyst, and sodium hydroxide as a salt group.146.6 g of bromobenzene was used for 50 g (0.47 mol) of m-toluidine, 146.6 g of bromobenzene,necessary for reaction with m-toluidine73.3 g (0.47 mol) of the above substrate was used as a reaction solvent, and 73.3 g of this excessive amount was used as a reaction solvent (1.5 times by mass with respect to m-toluidine)To the above amounts of m-toluidine and bromobenzene were added 0.33 g (0.47 mmol) of bisphosphorylphosphine dihydrochloride,And 46.7 g of sodium hydroxide (1. 17 mol) was added,The inside of the system was sufficiently replaced with nitrogen.After that, the temperature of the hot water bath was increased to 230 C. and the reaction was carried out for 8 hours.This reaction was carried out by using distillation tube to distill off the by-produced water to the outside of the system. During the reaction, the reaction did not suddenly boil. After completion of the reaction, the reaction was cooled and the excess bromobenzene was reduced After separating the aqueous layer, the heptane was distilled off under reduced pressure, and distillation was carried out. After distilling off the reaction product, heptane and water were added to the reaction product, and the reaction product was subjected to liquid separation operation to extract the reaction product into the heptane layer. Thereby, 3-methyldiphenylamine was obtained |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With palladium diacetate; potassium carbonate; In isopropyl alcohol; at 110℃; for 14h; | Step 1: Synthesis of Intermediate 1-15.1 3 -Methyl- diphenylamine R38 (1.0 g, 5.5 mmol), K2CO3 (75 mg, 0.55 mmol) and palladium acetate (37 mg, 0.16 mmol) in 2,2-dimethyl-l-propanol (5 mL) is is stirred at 110 C for 14 h. Water is added to the reaction mixture and extracted with dichloromethane. The combined organic layer is concentrated in vacuo, residue triturated with methanol/dichloromethane and dried in vacuo and directly taken to the next step. Yield 29%>, m/z 182 [M+H]+, rt 0.67 min, LC-MS Method X012 S01. |
29% | With palladium diacetate; potassium carbonate; at 110℃; for 14h; | 3-Methyl-diphenylamine R38 (1.0 g, 5.5 mmol), K2CO3 (75 mg, 0.55 mmol) and palladium acetate (37 mg, 0.16 mmol) in 2,2-dimethyl-1-propanol (5 mL) is stirred at 110 C. for 14 h. Water is added to the reaction mixture and extracted with dichloromethane. The combined organic layer is concentrated in vacuo, residue triturated with methanol/dichloromethane and dried in vacuo and directly taken to the next step. Yield 29%, m/z 182 [M+H]+, rt 0.67 min, LC-MS Method X012_S01. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With tetrabutylammomium bromide; palladium diacetate; potassium carbonate; 2,6-bis(diphenylphosphino)pyridine; In N,N-dimethyl acetamide; at 135℃; for 2h;Inert atmosphere;Catalytic behavior; | General procedure: A round bottomedflask was charged with bromobenzene (4 mmol), aniline (4 mmol),TBAB (3 mmol), and K2CO3 (4 mmol) under a dry nitrogen atmosphere. A solution of (Ph2P)2py (0.05 mol % in 2 mL of DMAc) and a solution of palladiumacetate (0.025 mol % in 2 mL of DMAc) was added through a rubber septum,and the resulting mixture was heated at 135 C for the appropriate time. Uponcompletion of the reaction, the mixture was cooled to room temperature and quenched with H2O. After extraction with CH2Cl2 (3 20 mL), the combinedorganic layer was dried over MgSO4. The solvent was evaporated and the cruderesidue was purified by silica gel chromatography, using n-hexane/EtOAc aseluent to provide the desired product. The products were characterized byNMR spectroscopy |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With tri-tert-butyl phosphine; 5%-palladium/activated carbon; sodium t-butanolate; In o-xylene; at 110℃; for 2h;Inert atmosphere;Catalytic behavior; | A cooling tube, round bottom flask 50mL equipped with athermometer, at room temperature, bromobenzene 1.4g in a nitrogen atmosphere(9.0 mmol), 3- methyl-diphenylamine 1.1 g (6.0 mmol), palladium supported materialB 0 .13g (palladium atom 0.12mmol), was mixed with sodium -tert- butoxide 0.86g(9.0mmol) and o- xylene 6.0g. After nitrogen is a flow of about 20 minutes, tri(tert- butyl) phosphine (hereinafter, "P- (tBu) 3" and also indicate)36.4 mg (0.18 mmol) was dissolved o- xylene ( 150 uL) was added and undernormal pressure, pressurized to 110 C.It was raised and the mixture was stirred for 2 hours after.Incidentally, the yield by gas chromatography, was calculated by internalstandard method with an internal standard substance n- eicosane. The resultsare shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With tri-tert-butyl phosphine; 5%-palladium/activated carbon; sodium t-butanolate; In o-xylene; at 110℃; for 2h;Inert atmosphere; | A cooling tube, round bottom flask 50mL equipped with athermometer, at room temperature, bromobenzene 1.4g in a nitrogen atmosphere(9.0 mmol), 3- methyl-diphenylamine 1.1 g (6.0 mmol), palladium supported materialB 0 .13g (palladium atom 0.12mmol), was mixed with sodium -tert- butoxide 0.86g(9.0mmol) and o- xylene 6.0g. After nitrogen is a flow of about 20 minutes, tri(tert- butyl) phosphine (hereinafter, "P- (tBu) 3" and also indicate)36.4 mg (0.18 mmol) was dissolved o- xylene ( 150 uL) was added and undernormal pressure, pressurized to 110 C.It was raised and the mixture was stirred for 2 hours after.Incidentally, the yield by gas chromatography, was calculated by internalstandard method with an internal standard substance n- eicosane. The resultsare shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.2% | With sodium t-butanolate;palladium diacetate; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride; In toluene; at 20 - 130℃;Inert atmosphere; | 3.0 g (30 mmol) of sodium tert-butoxide, 217 mg (0.5 mmol) of IPr-HCl (compound No. 1), 45 mg (0.2 mmol) of palladium(II) acetate, 3.67 g (20 mmol) of 3-methyldiphenylamine, 3.2 g (10 mmol) of 4,4'-dibromobiphenyl and 30 ml of toluene were put into a 50-ml three-neck flask equipped with a stirrer, a condenser tube, a thermometer and a gas-introducing duct, in an argon current at room temperature, and reacted under reflux in an oil bath controlled at a temperature of 130°C for 7 hours. The reaction liquid was cooled to room temperature, then left overnight at room temperature, and 150 ml of methylene chloride was added thereto. The insoluble matter was removed by filtration, and the filtrate was washed twice with 50 ml of water. This was dewatered and dried with 30 g of anhydrous sodium sulfate, and the solvent was evaporated away to give a residue. The residue was purified through column chromatography (carrier, Fuji Silicia's NH silica gel 150 g; eluent, cyclohexane) to give 4.4 g of N,N'-diphenyl-N,N'-di(m-tolyl)benzidine (TPD) (yield 85.2percent). |
51% | In a 100 ml flask purged with a nitrogen atmosphere,30 g of xylene, 7.33 g (40 mmol) of N- (3-methylphenyl) aniline, 0.96 g (40 mmol) of sodium hydride,7.36 g (40 mmol) of magnesium bromide was charged,The reaction solution was heated to 140 ° C. while stirring.After aging for 2 hours at the same temperature, 0.063 g (0.5 mmol) of iron (II) chloride,3.12 g (10 mmol) of 4,4'-dibromobiphenyl was added,Further aging was carried out for 14 hours at the same temperature. After completion of the reaction,After cooling, water was added to dissolve the salt and liquid separation was carried out. After separating the organic layer,As a result of analysis by GC using the internal standard method,Bis (3-methylphenylphenylamino) biphenyl as a target product was produced in a yield of 51percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.3% | With benzyltriphenylphosphonium chloride; potassium carbonate;copper(l) iodide; at 200 - 210℃; for 12h; | Example 10 Synthesis of Tris{4-[N-(3-methylphenyl)-N-phenylamino]phenyl}amine (exemplified compound I-25) Tris(4-bromophenyl)amine was mixed in an amount of 8.2 g (17.0 mmol) with 18.7 g (102.0 mmol) of N-(3-methylphenyl)-N-phenylamine, 13.5 g (102.0 mmol) of potassium carbonate, 0.5 g (2.6 mmol) of copper iodide, and 1.0 g (2.6 mmol) of benzyltriphenylphosphonium chloride. This mixture was reacted at 200-210 C. for 12 hours in a nitrogen stream. After the reaction, 100 mL of toluene and 50 mL of water were added and the resultant mixture was subjected to liquid separation. Thereafter, the organic layer was washed with water and dehydrated and dried with anhydrous sodium sulfate. After the drying agent was removed by filtration, 100 mL of hexane was added to the organic layer. The resultant solution was cooled for crystallization. Thus, the target compound (I-25) was obtained as light-yellow crude crystals in an amount of 7.9 g (yield, 85.3%). The target compound obtained had a melting point of 210-211 C. and a content as determined by HPLC of 99.2% (HPLC conditions: column, Super-ODS; eluent, methanol/tetrahydrofuran (V/V=97/3); buffer, triethylamine and acetic acid each in an amount of 0.1%; detection UV, 254 nm; flow rate, 0.8 mL/min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With tri-tert-butyl phosphine; 5%-palladium/activated carbon; sodium t-butanolate; In o-xylene; at 110℃; for 2h;Inert atmosphere; | A cooling tube, round bottom flask 50mL equipped with athermometer, at room temperature, bromobenzene 1.4g in a nitrogen atmosphere(9.0 mmol), 3- methyl-diphenylamine 1.1 g (6.0 mmol), palladium supported materialB 0 .13g (palladium atom 0.12mmol), was mixed with sodium -tert- butoxide 0.86g(9.0mmol) and o- xylene 6.0g. After nitrogen is a flow of about 20 minutes, tri(tert- butyl) phosphine (hereinafter, "P- (tBu) 3" and also indicate)36.4 mg (0.18 mmol) was dissolved o- xylene ( 150 uL) was added and undernormal pressure, pressurized to 110 C.It was raised and the mixture was stirred for 2 hours after.Incidentally, the yield by gas chromatography, was calculated by internalstandard method with an internal standard substance n- eicosane. The resultsare shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper; potassium carbonate;PEG-6000; In 1,2-dichloro-benzene; for 22h;Heating / reflux; | (Synthetic Example 1) N,N'-diphenyl-N,N'-bis(3-tolyl)-4,4'-diaminobiphenyl (3,3-TPD) was synthesized as follows. 1.0g (2.46mmol) of 4,4'-diiodobiphenyl and 20 ml of o-dichlorobenzene were added to a 100 ml four-necked flask made of glass. Furthermore 1.08g (5.90mmol) of m-methyldiphenylamine, 0.104g of poly(ethylene glycol) PEG-6000 as a reaction accelerator that was available from Wako Pure Chemical Industries, Ltd., 2.73g (0.0198mol) of potassium carbonate and 0.635g (9.87mmol) of powdered copper were added thereto. It was determined for tracing by the high-speed liquid chromatography. And it was stirred and refluxed for 22 hours until no peaks of starting materials and intermediates were determined. It was filtrated at the hot temperature. The product was washed with dichloromethane until color of the filtrate was to be light. The solvent was distilled under reduced pressure. Residual product was purified by silica gel column chromatography to obtain 3,3-TPD that is represented by Compound Example 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With palladium diacetate; tri-tert-butyl phosphine; sodium t-butanolate In toluene for 48h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With bis{1,1?-dimethyl-3,3?-methylenediimidazoline-2,2?-diylidene}nickel(II) dibromide; potassium tert-butylate; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere; Schlenk technique;Catalytic behavior; | General procedure: Under an N2 atmosphere, KOtBu (1.3 mmol), complex 1 (1 mol %), dioxane (2 ml), amines (1.3 mmol) and aryl chlorides (1.0 mmol) were successively added into a Schlenk tube. The mixture was stirred vigorously at 90 C for 4 h. Then the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (eluent: PE/EA = 15:1) to give the pure products. The reported yields are the average of two runs. |
94% | With C19H14N4NiO2; potassium tert-butylate; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere; Schlenk technique; | General procedure: Under an N2atmosphere, KOtBu (1.3 mmol), complex 1 (1 mol%),dioxane (2 ml), amines (1.3 mmol) and aryl chlorides (1.0 mmol)were successively added into a Schlenk tube. The mixture wasstirred vigorously at 90C for 4 h. Then the solvent was removedunder reduced pressure and the residue was purified by columnchromatography on silica gel (eluent:PE/EA = 15:1) to give the pureproducts. The reported yields are the average of two runs.The catalytic reactions have been given in Tables 4-7. The result-ing amines were identified by comparison of the1H and13C NMRdata with those previously reported (ESI). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20 - 25.5%Chromat.; 5 - 9%Chromat. | With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); 2?-(diphenylphosphino)-N,N?-dimethyl-(1,1?-biphenyl)-2-amine; In 1,2-dimethoxyethane; at 100℃; for 21h; | This example illustrates the tandem Ir-catalyzed borylation and catalytic amination process. [0064] 3-Aminoboronic acids and esters as shown below are of interest as evidenced by the large number of derivatives synthesized, and by several patents, which note their activity as O-lactamase inhibitors (See, for example, Shoichet et al., WO0035905). Few in number, however, are 1, 3, 5-aminoboronic acids and esters (about 25 compounds by SCIFINDER SCHOLAR). Such substrates may prove useful for further derivatization as they can possess three unique sites for diversity. Furthermore, these compounds may prove ideal as scaffolds for combinatorial libraries. The boronic acid or ester can be transformed into a myriad of functionalities including aryl or vinyl via the Suzuki-Miyuara coupling (Miyaura and Suzuki, Chem. Rev. 95: 2457-2483 (1995); Suzuki, J. Organomet. Chem. 576: 147-168 (1999); Miyaura, In Advances in Metal-Organic Chemistry: Liebeskind, Ed.: JAI: London,; Vol. 6, pp. 187-243 (1998)). If R is a halogen, then there exists a multitude of coupling opportunities (See, for examples, Metal-catalyzed Cross-coupling Reactions; Diederich and Stang, eds.: Wiley: Wienheim, 1998). [0066] Recently, a catalytic aromatic C-H activation/borylation reaction utilizing Ir- or Rh-catalysts was developed. The process is high yielding, functional group tolerant (alkyl, halo, carboxy, alkoxy, and protected amino), chemoselective (1,3-substited arenes give only the 5-boryl product), and efficient (Iverson and Smith, J. Am. Chem. Soc. 121: 7696-7697 (1999); Cho et al., J. Am. Chem. Soc. 122: 12868-12869 (2000); Tse et al., Org. Lett. 3: 2831 (2001); Chao et al., Science 295: 305-308 (2002)). Furthermore, the process allows for the direct construction of aryl boronic esters from hydrocarbon feedstocks without going through an aryl halide. Scheme 2 depicts a prototypical borylation reaction: borylation of benzene using (Ind)Ir(COD)(2 mol %), dppe (2 mol %). The borane of choice is pinacolborane (HBPin). A variety of Ir(I) catalysts can be used, including [Ir(COD)Cl]2, Ir(Indenyl)(C2H4)2, Ir(Indenyl)dppe, and (Indenyl)Ir(COD), in the presence of 2 mol equivalents of PMe3 or 1 mol equivalent of a bidentate ligand like dmpe or dppe. The catalyst system of choice is (Indenyl)Ir(COD), dppe or dmpe (2 mol % each) because of it's cleanness of reaction and efficient TOF (24 h-1 with benzene). The reaction can be run in the neat arene or in inert solvents (e.g. cyclohexane). During our studies into tandem borylation/Suzuki coupling, we noted difficulties with the hydrolysis of the boronic ester functionality (Bpin). The robustness of the BPin group suggested that, perhaps, the pinacol might serve as a protecting group for the boron. Thus, it was deemed of interest to explore other catalytic transformations in the presence of the BPin group. One such transformation is the Buchwald-Hartwig amination of aryl halides (See, for example; Wolfe et al.,. J. Org. Chem. 65: 1158 (2000); Hartwig et al., J. Org. Chem. 64: 5575 (1999); Wolfe and Buchwald, Angew. Chem. Int. Ed. 38: 2413 (1999)). Initially, the reaction was attempted on pure 1-chloro-3-methylphenyl-5-BPin. As shown in Scheme 3 (Buchwald-Hartwig coupling of 1-chloro-3-methylphenyl-5-BPin with aniline), application of Buchwalds protocol proceeded cleanly to give the desired cross-coupling product in 64.7% and 63.8% yield. The use of PtBu3 improved the yield to 78.8%. Unfortunately, initial attempts to perform the reaction in the ?one-pot? protocol were unsuccessful. Table 1 summarizes the results. In all cases where K3PO4.nH2O was used, a significant amount of pinacol was observed by GC-FID (Entries 1-5). While this is indicative of reaction of the BPin group and is most likely a by-product of Suzuki coupling (in this case, dimerization or oligiomerization of the starting material), no dimers or oligiomers were isolated. Noteworthy, is the formation of the desired product, albeit in low yield (10% GC-FID ratio), using K3PO4.nH2O and PtBu3 when all other attempts using the base failed. With anhydrous K3PO4, results were better (Entries 6-9). Most importantly, no pinacol was formed in these reactions. Changing the base or increasing catalyst loading did not improve the results. The use of PtBu3 led to the best results and after 4 days at 100 C., 34.4% of the desired product was isolated (Entry 10). This result, however, falls short of the reaction performed on pure material and shows that the by-products from the Ir-catalyzed borylation are not completely innocuous. As was previously mentioned, a potential source of concern is the presence of free bidentate phosphines after the borylation, which may interfere with subsequent reactions. In the tandem Suzuki reactions, an aryl chloride was successfully coupled only when dmpe was used as the Ir ligand. Thus, the tandem borylation/Buchwald-Hartwig amination reaction of the present invention was attempted using the (Ind)Ir(COD)/dmpe precatalyst.... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11%Chromat.; 15%Chromat.; 11%Chromat.; 6%Chromat. | With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; 2?-(diphenylphosphino)-N,N?-dimethyl-(1,1?-biphenyl)-2-amine; In 1,2-dimethoxyethane; at 100℃; for 21h; | This example illustrates the tandem Ir-catalyzed borylation and catalytic amination process. [0064] 3-Aminoboronic acids and esters as shown below are of interest as evidenced by the large number of derivatives synthesized, and by several patents, which note their activity as O-lactamase inhibitors (See, for example, Shoichet et al., WO0035905). Few in number, however, are 1, 3, 5-aminoboronic acids and esters (about 25 compounds by SCIFINDER SCHOLAR). Such substrates may prove useful for further derivatization as they can possess three unique sites for diversity. Furthermore, these compounds may prove ideal as scaffolds for combinatorial libraries. The boronic acid or ester can be transformed into a myriad of functionalities including aryl or vinyl via the Suzuki-Miyuara coupling (Miyaura and Suzuki, Chem. Rev. 95: 2457-2483 (1995); Suzuki, J. Organomet. Chem. 576: 147-168 (1999); Miyaura, In Advances in Metal-Organic Chemistry: Liebeskind, Ed.: JAI: London,; Vol. 6, pp. 187-243 (1998)). If R is a halogen, then there exists a multitude of coupling opportunities (See, for examples, Metal-catalyzed Cross-coupling Reactions; Diederich and Stang, eds.: Wiley: Wienheim, 1998). [0066] Recently, a catalytic aromatic C-H activation/borylation reaction utilizing Ir- or Rh-catalysts was developed. The process is high yielding, functional group tolerant (alkyl, halo, carboxy, alkoxy, and protected amino), chemoselective (1,3-substited arenes give only the 5-boryl product), and efficient (Iverson and Smith, J. Am. Chem. Soc. 121: 7696-7697 (1999); Cho et al., J. Am. Chem. Soc. 122: 12868-12869 (2000); Tse et al., Org. Lett. 3: 2831 (2001); Chao et al., Science 295: 305-308 (2002)). Furthermore, the process allows for the direct construction of aryl boronic esters from hydrocarbon feedstocks without going through an aryl halide. Scheme 2 depicts a prototypical borylation reaction: borylation of benzene using (Ind)Ir(COD)(2 mol %), dppe (2 mol %). The borane of choice is pinacolborane (HBPin). A variety of Ir(I) catalysts can be used, including [Ir(COD)Cl]2, Ir(Indenyl)(C2H4)2, Ir(Indenyl)dppe, and (Indenyl)Ir(COD), in the presence of 2 mol equivalents of PMe3 or 1 mol equivalent of a bidentate ligand like dmpe or dppe. The catalyst system of choice is (Indenyl)Ir(COD), dppe or dmpe (2 mol % each) because of it's cleanness of reaction and efficient TOF (24 h-1 with benzene). The reaction can be run in the neat arene or in inert solvents (e.g. cyclohexane). During our studies into tandem borylation/Suzuki coupling, we noted difficulties with the hydrolysis of the boronic ester functionality (Bpin). The robustness of the BPin group suggested that, perhaps, the pinacol might serve as a protecting group for the boron. Thus, it was deemed of interest to explore other catalytic transformations in the presence of the BPin group. One such transformation is the Buchwald-Hartwig amination of aryl halides (See, for example; Wolfe et al.,. J. Org. Chem. 65: 1158 (2000); Hartwig et al., J. Org. Chem. 64: 5575 (1999); Wolfe and Buchwald, Angew. Chem. Int. Ed. 38: 2413 (1999)). Initially, the reaction was attempted on pure 1-chloro-3-methylphenyl-5-BPin. As shown in Scheme 3 (Buchwald-Hartwig coupling of 1-chloro-3-methylphenyl-5-BPin with aniline), application of Buchwalds protocol proceeded cleanly to give the desired cross-coupling product in 64.7% and 63.8% yield. The use of PtBu3 improved the yield to 78.8%. Unfortunately, initial attempts to perform the reaction in the ?one-pot? protocol were unsuccessful. Table 1 summarizes the results. In all cases where K3PO4.nH2O was used, a significant amount of pinacol was observed by GC-FID (Entries 1-5). While this is indicative of reaction of the BPin group and is most likely a by-product of Suzuki coupling (in this case, dimerization or oligiomerization of the starting material), no dimers or oligiomers were isolated. Noteworthy, is the formation of the desired product, albeit in low yield (10% GC-FID ratio), using K3PO4.nH2O and PtBu3 when all other attempts using the base failed. With anhydrous K3PO4, results were better (Entries 6-9). Most importantly, no pinacol was formed in these reactions. Changing the base or increasing catalyst loading did not improve the results. The use of PtBu3 led to the best results and after 4 days at 100 C., 34.4% of the desired product was isolated (Entry 10). This result, however, falls short of the reaction performed on pure material and shows that the by-products from the Ir-catalyzed borylation are not completely innocuous. As was previously mentioned, a potential source of concern is the presence of free bidentate phosphines after the borylation, which may interfere with subsequent reactions. In the tandem Suzuki reactions, an aryl chloride was successfully coupled only when dmpe was used as the Ir ligand. Thus, the tandem borylation/Buchwald-Hartwig amination reaction of the present invention was attempted using the (Ind)Ir(COD)/dmpe precatalyst.... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14 - 27%Chromat.; 3 - 5%Chromat.; 4%Chromat. | With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); 2?-(diphenylphosphino)-N,N?-dimethyl-(1,1?-biphenyl)-2-amine; In 1,2-dimethoxyethane; at 100℃; for 21h; | This example illustrates the tandem Ir-catalyzed borylation and catalytic amination process. [0064] 3-Aminoboronic acids and esters as shown below are of interest as evidenced by the large number of derivatives synthesized, and by several patents, which note their activity as O-lactamase inhibitors (See, for example, Shoichet et al., WO0035905). Few in number, however, are 1, 3, 5-aminoboronic acids and esters (about 25 compounds by SCIFINDER SCHOLAR). Such substrates may prove useful for further derivatization as they can possess three unique sites for diversity. Furthermore, these compounds may prove ideal as scaffolds for combinatorial libraries. The boronic acid or ester can be transformed into a myriad of functionalities including aryl or vinyl via the Suzuki-Miyuara coupling (Miyaura and Suzuki, Chem. Rev. 95: 2457-2483 (1995); Suzuki, J. Organomet. Chem. 576: 147-168 (1999); Miyaura, In Advances in Metal-Organic Chemistry: Liebeskind, Ed.: JAI: London,; Vol. 6, pp. 187-243 (1998)). If R is a halogen, then there exists a multitude of coupling opportunities (See, for examples, Metal-catalyzed Cross-coupling Reactions; Diederich and Stang, eds.: Wiley: Wienheim, 1998). [0066] Recently, a catalytic aromatic C-H activation/borylation reaction utilizing Ir- or Rh-catalysts was developed. The process is high yielding, functional group tolerant (alkyl, halo, carboxy, alkoxy, and protected amino), chemoselective (1,3-substited arenes give only the 5-boryl product), and efficient (Iverson and Smith, J. Am. Chem. Soc. 121: 7696-7697 (1999); Cho et al., J. Am. Chem. Soc. 122: 12868-12869 (2000); Tse et al., Org. Lett. 3: 2831 (2001); Chao et al., Science 295: 305-308 (2002)). Furthermore, the process allows for the direct construction of aryl boronic esters from hydrocarbon feedstocks without going through an aryl halide. Scheme 2 depicts a prototypical borylation reaction: borylation of benzene using (Ind)Ir(COD)(2 mol %), dppe (2 mol %). The borane of choice is pinacolborane (HBPin). A variety of Ir(I) catalysts can be used, including [Ir(COD)Cl]2, Ir(Indenyl)(C2H4)2, Ir(Indenyl)dppe, and (Indenyl)Ir(COD), in the presence of 2 mol equivalents of PMe3 or 1 mol equivalent of a bidentate ligand like dmpe or dppe. The catalyst system of choice is (Indenyl)Ir(COD), dppe or dmpe (2 mol % each) because of it's cleanness of reaction and efficient TOF (24 h-1 with benzene). The reaction can be run in the neat arene or in inert solvents (e.g. cyclohexane). During our studies into tandem borylation/Suzuki coupling, we noted difficulties with the hydrolysis of the boronic ester functionality (Bpin). The robustness of the BPin group suggested that, perhaps, the pinacol might serve as a protecting group for the boron. Thus, it was deemed of interest to explore other catalytic transformations in the presence of the BPin group. One such transformation is the Buchwald-Hartwig amination of aryl halides (See, for example; Wolfe et al.,. J. Org. Chem. 65: 1158 (2000); Hartwig et al., J. Org. Chem. 64: 5575 (1999); Wolfe and Buchwald, Angew. Chem. Int. Ed. 38: 2413 (1999)). Initially, the reaction was attempted on pure 1-chloro-3-methylphenyl-5-BPin. As shown in Scheme 3 (Buchwald-Hartwig coupling of 1-chloro-3-methylphenyl-5-BPin with aniline), application of Buchwalds protocol proceeded cleanly to give the desired cross-coupling product in 64.7% and 63.8% yield. The use of PtBu3 improved the yield to 78.8%. Unfortunately, initial attempts to perform the reaction in the ?one-pot? protocol were unsuccessful. Table 1 summarizes the results. In all cases where K3PO4.nH2O was used, a significant amount of pinacol was observed by GC-FID (Entries 1-5). While this is indicative of reaction of the BPin group and is most likely a by-product of Suzuki coupling (in this case, dimerization or oligiomerization of the starting material), no dimers or oligiomers were isolated. Noteworthy, is the formation of the desired product, albeit in low yield (10% GC-FID ratio), using K3PO4.nH2O and PtBu3 when all other attempts using the base failed. With anhydrous K3PO4, results were better (Entries 6-9). Most importantly, no pinacol was formed in these reactions. Changing the base or increasing catalyst loading did not improve the results. The use of PtBu3 led to the best results and after 4 days at 100 C., 34.4% of the desired product was isolated (Entry 10). This result, however, falls short of the reaction performed on pure material and shows that the by-products from the Ir-catalyzed borylation are not completely innocuous. As was previously mentioned, a potential source of concern is the presence of free bidentate phosphines after the borylation, which may interfere with subsequent reactions. In the tandem Suzuki reactions, an aryl chloride was successfully coupled only when dmpe was used as the Ir ligand. Thus, the tandem borylation/Buchwald-Hartwig amination reaction of the present invention was attempted using the (Ind)Ir(COD)/dmpe precatalyst.... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8 - 23%Chromat.; 3%Chromat.; 4 - 21%Chromat. | With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); 2?-(diphenylphosphino)-N,N?-dimethyl-(1,1?-biphenyl)-2-amine; In 1,2-dimethoxyethane; at 100℃; for 21 - 48h; | This example illustrates the tandem Ir-catalyzed borylation and catalytic amination process. [0064] 3-Aminoboronic acids and esters as shown below are of interest as evidenced by the large number of derivatives synthesized, and by several patents, which note their activity as O-lactamase inhibitors (See, for example, Shoichet et al., WO0035905). Few in number, however, are 1, 3, 5-aminoboronic acids and esters (about 25 compounds by SCIFINDER SCHOLAR). Such substrates may prove useful for further derivatization as they can possess three unique sites for diversity. Furthermore, these compounds may prove ideal as scaffolds for combinatorial libraries. The boronic acid or ester can be transformed into a myriad of functionalities including aryl or vinyl via the Suzuki-Miyuara coupling (Miyaura and Suzuki, Chem. Rev. 95: 2457-2483 (1995); Suzuki, J. Organomet. Chem. 576: 147-168 (1999); Miyaura, In Advances in Metal-Organic Chemistry: Liebeskind, Ed.: JAI: London,; Vol. 6, pp. 187-243 (1998)). If R is a halogen, then there exists a multitude of coupling opportunities (See, for examples, Metal-catalyzed Cross-coupling Reactions; Diederich and Stang, eds.: Wiley: Wienheim, 1998). [0066] Recently, a catalytic aromatic C-H activation/borylation reaction utilizing Ir- or Rh-catalysts was developed. The process is high yielding, functional group tolerant (alkyl, halo, carboxy, alkoxy, and protected amino), chemoselective (1,3-substited arenes give only the 5-boryl product), and efficient (Iverson and Smith, J. Am. Chem. Soc. 121: 7696-7697 (1999); Cho et al., J. Am. Chem. Soc. 122: 12868-12869 (2000); Tse et al., Org. Lett. 3: 2831 (2001); Chao et al., Science 295: 305-308 (2002)). Furthermore, the process allows for the direct construction of aryl boronic esters from hydrocarbon feedstocks without going through an aryl halide. Scheme 2 depicts a prototypical borylation reaction: borylation of benzene using (Ind)Ir(COD)(2 mol %), dppe (2 mol %). The borane of choice is pinacolborane (HBPin). A variety of Ir(I) catalysts can be used, including [Ir(COD)Cl]2, Ir(Indenyl)(C2H4)2, Ir(Indenyl)dppe, and (Indenyl)Ir(COD), in the presence of 2 mol equivalents of PMe3 or 1 mol equivalent of a bidentate ligand like dmpe or dppe. The catalyst system of choice is (Indenyl)Ir(COD), dppe or dmpe (2 mol % each) because of it's cleanness of reaction and efficient TOF (24 h-1 with benzene). The reaction can be run in the neat arene or in inert solvents (e.g. cyclohexane). During our studies into tandem borylation/Suzuki coupling, we noted difficulties with the hydrolysis of the boronic ester functionality (Bpin). The robustness of the BPin group suggested that, perhaps, the pinacol might serve as a protecting group for the boron. Thus, it was deemed of interest to explore other catalytic transformations in the presence of the BPin group. One such transformation is the Buchwald-Hartwig amination of aryl halides (See, for example; Wolfe et al.,. J. Org. Chem. 65: 1158 (2000); Hartwig et al., J. Org. Chem. 64: 5575 (1999); Wolfe and Buchwald, Angew. Chem. Int. Ed. 38: 2413 (1999)). Initially, the reaction was attempted on pure 1-chloro-3-methylphenyl-5-BPin. As shown in Scheme 3 (Buchwald-Hartwig coupling of 1-chloro-3-methylphenyl-5-BPin with aniline), application of Buchwalds protocol proceeded cleanly to give the desired cross-coupling product in 64.7% and 63.8% yield. The use of PtBu3 improved the yield to 78.8%. Unfortunately, initial attempts to perform the reaction in the ?one-pot? protocol were unsuccessful. Table 1 summarizes the results. In all cases where K3PO4.nH2O was used, a significant amount of pinacol was observed by GC-FID (Entries 1-5). While this is indicative of reaction of the BPin group and is most likely a by-product of Suzuki coupling (in this case, dimerization or oligiomerization of the starting material), no dimers or oligiomers were isolated. Noteworthy, is the formation of the desired product, albeit in low yield (10% GC-FID ratio), using K3PO4.nH2O and PtBu3 when all other attempts using the base failed. With anhydrous K3PO4, results were better (Entries 6-9). Most importantly, no pinacol was formed in these reactions. Changing the base or increasing catalyst loading did not improve the results. The use of PtBu3 led to the best results and after 4 days at 100 C., 34.4% of the desired product was isolated (Entry 10). This result, however, falls short of the reaction performed on pure material and shows that the by-products from the Ir-catalyzed borylation are not completely innocuous. As was previously mentioned, a potential source of concern is the presence of free bidentate phosphines after the borylation, which may interfere with subsequent reactions. In the tandem Suzuki reactions, an aryl chloride was successfully coupled only when dmpe was used as the Ir ligand. Thus, the tandem borylation/Buchwald-Hartwig amination reaction of the present invention was attempted using the (Ind)Ir(COD)/dmpe precatalyst.... |
9%Chromat.; 19%Chromat.; 2%Chromat. | With potassium tert-butylate;tris-(dibenzylideneacetone)dipalladium(0); 2?-(diphenylphosphino)-N,N?-dimethyl-(1,1?-biphenyl)-2-amine; at 100℃; for 21h; | This example illustrates the tandem Ir-catalyzed borylation and catalytic amination process. [0064] 3-Aminoboronic acids and esters as shown below are of interest as evidenced by the large number of derivatives synthesized, and by several patents, which note their activity as O-lactamase inhibitors (See, for example, Shoichet et al., WO0035905). Few in number, however, are 1, 3, 5-aminoboronic acids and esters (about 25 compounds by SCIFINDER SCHOLAR). Such substrates may prove useful for further derivatization as they can possess three unique sites for diversity. Furthermore, these compounds may prove ideal as scaffolds for combinatorial libraries. The boronic acid or ester can be transformed into a myriad of functionalities including aryl or vinyl via the Suzuki-Miyuara coupling (Miyaura and Suzuki, Chem. Rev. 95: 2457-2483 (1995); Suzuki, J. Organomet. Chem. 576: 147-168 (1999); Miyaura, In Advances in Metal-Organic Chemistry: Liebeskind, Ed.: JAI: London,; Vol. 6, pp. 187-243 (1998)). If R is a halogen, then there exists a multitude of coupling opportunities (See, for examples, Metal-catalyzed Cross-coupling Reactions; Diederich and Stang, eds.: Wiley: Wienheim, 1998). [0066] Recently, a catalytic aromatic C-H activation/borylation reaction utilizing Ir- or Rh-catalysts was developed. The process is high yielding, functional group tolerant (alkyl, halo, carboxy, alkoxy, and protected amino), chemoselective (1,3-substited arenes give only the 5-boryl product), and efficient (Iverson and Smith, J. Am. Chem. Soc. 121: 7696-7697 (1999); Cho et al., J. Am. Chem. Soc. 122: 12868-12869 (2000); Tse et al., Org. Lett. 3: 2831 (2001); Chao et al., Science 295: 305-308 (2002)). Furthermore, the process allows for the direct construction of aryl boronic esters from hydrocarbon feedstocks without going through an aryl halide. Scheme 2 depicts a prototypical borylation reaction: borylation of benzene using (Ind)Ir(COD)(2 mol %), dppe (2 mol %). The borane of choice is pinacolborane (HBPin). A variety of Ir(I) catalysts can be used, including [Ir(COD)Cl]2, Ir(Indenyl)(C2H4)2, Ir(Indenyl)dppe, and (Indenyl)Ir(COD), in the presence of 2 mol equivalents of PMe3 or 1 mol equivalent of a bidentate ligand like dmpe or dppe. The catalyst system of choice is (Indenyl)Ir(COD), dppe or dmpe (2 mol % each) because of it's cleanness of reaction and efficient TOF (24 h-1 with benzene). The reaction can be run in the neat arene or in inert solvents (e.g. cyclohexane). During our studies into tandem borylation/Suzuki coupling, we noted difficulties with the hydrolysis of the boronic ester functionality (Bpin). The robustness of the BPin group suggested that, perhaps, the pinacol might serve as a protecting group for the boron. Thus, it was deemed of interest to explore other catalytic transformations in the presence of the BPin group. One such transformation is the Buchwald-Hartwig amination of aryl halides (See, for example; Wolfe et al.,. J. Org. Chem. 65: 1158 (2000); Hartwig et al., J. Org. Chem. 64: 5575 (1999); Wolfe and Buchwald, Angew. Chem. Int. Ed. 38: 2413 (1999)). Initially, the reaction was attempted on pure 1-chloro-3-methylphenyl-5-BPin. As shown in Scheme 3 (Buchwald-Hartwig coupling of 1-chloro-3-methylphenyl-5-BPin with aniline), application of Buchwalds protocol proceeded cleanly to give the desired cross-coupling product in 64.7% and 63.8% yield. The use of PtBu3 improved the yield to 78.8%. Unfortunately, initial attempts to perform the reaction in the ?one-pot? protocol were unsuccessful. Table 1 summarizes the results. In all cases where K3PO4.nH2O was used, a significant amount of pinacol was observed by GC-FID (Entries 1-5). While this is indicative of reaction of the BPin group and is most likely a by-product of Suzuki coupling (in this case, dimerization or oligiomerization of the starting material), no dimers or oligiomers were isolated. Noteworthy, is the formation of the desired product, albeit in low yield (10% GC-FID ratio), using K3PO4.nH2O and PtBu3 when all other attempts using the base failed. With anhydrous K3PO4, results were better (Entries 6-9). Most importantly, no pinacol was formed in these reactions. Changing the base or increasing catalyst loading did not improve the results. The use of PtBu3 led to the best results and after 4 days at 100 C., 34.4% of the desired product was isolated (Entry 10). This result, however, falls short of the reaction performed on pure material and shows that the by-products from the Ir-catalyzed borylation are not completely innocuous. As was previously mentioned, a potential source of concern is the presence of free bidentate phosphines after the borylation, which may interfere with subsequent reactions. In the tandem Suzuki reactions, an aryl chloride was successfully coupled only when dmpe was used as the Ir ligand. Thus, the tandem borylation/Buchwald-Hartwig amination reaction of the present invention was attempted using the (Ind)Ir(COD)/dmpe precatalyst.... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10% | Stage #1: 3,6-dibromo-9-ethyl-9H-carbazole; 3-Methyldiphenylamine With copper(l) iodide; trans-1,2-cyclohexanediamine In xylene at 160℃; for 0.5h; Stage #2: With potassium phosphate In xylene for 216h; | 1.1 In an atmosphere of argon, 16.59 g (30 mmol) of N-ethyl-3,6- dibromocarbazole and 12.09 g (66 mmol) of 3-methyldiphenylamine were dissolved in 100ml of dehydrated xylene. Then, 5.7 g (30 mmol) of copper iodide and 22.8 g (200 mmol) of trans-cyclohexanediamine were added to the xylene solution, and stirring was performed at 160 °C for 30 minutes. After the stirring, 27.6 g (130 mmol) of potassium phosphate was added, and stirring was performed further for 9 days. After the stirring and cooling to room temperature, 300 ml of toluene was added, and a precipitated object was filtered. The obtained filtrate was condensed, diethyl ether was added to the filtrate, and a precipitated object was filtered. Then, when methanol was added to the obtained filtrate, a tarry object was precipitated on a surface of the beaker. The filtrate with the tarry object was left at rest overnight, and the liquid phase was removed by decantation to obtain the tarry object. This obtained tarry object was purified by silica gel column chromatography using hexane: chloroform (1: 2) to obtain 3, 6-bis [N- (3-methylphenyl)-N-phenylamino]-9-ethylcarbazole (the above structure formula (56); hereinafter, referred to as EtCzmP2) that is light green powder. The obtained EtCzmP2 was purified by sublimation while setting at a higher temperature of 300 °C and a lower temperature of 200 °C. The yield after the purification by sublimation was approximately 10 %. It was determined according to a thermogravimetry-differential thermal analysis (TG-DTA) measurement that the thermal decomposition temperature of the obtained EtCzmP2 was 310 °C. When vacuum deposition was used to deposit the carbazole derivative, it was possible to form an uniform film. When fluorescence spectrums of a thin film and solution (solvent: methanol) of the obtained EtCzmP2 were measured, the obtained fluorescence spectrums respectively had a maximum peak at 435 nm with respect to an excitation wavelength (312 nm) in the case of the thin film and a maximum peak at 400 nm with respect to an excitation wavelength (290 nm) in the case of the solution (Fig. 2). In addition, when UV-Vis absorption spectrums of the thin film and solution (solvent: methanol) of the obtained EtCzmP2 were measured, a maximum absorption wavelength of 312 nm was obtained in the case of the thin film and a maximum absorption wavelength of 303 nm was obtained in the case of the solution (Fig. 3). Further, the value of a HOMO level that was measured by using Electron Spectrometer for Chemical Analysis AC-2 (from Riken Keiki Co. , Ltd. ) is-5.18 eV In addition, the value of a LUMO level that was estimated by adding the value of an absorption edge of the absorption spectrum (Fig. 3), as an energy gap, to the value of the HOMO level is-1.71 eV. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(Synthetic Example 3) The mixture of 3,3-TPD, 4,4-TPD and N,N'-diphenyl-N-(3-tolyl)-N'-(4-tolyl)-4,4'-diaminobiphenyl (3,4-TPD) that is represented by Compound Example 3 was synthesized as follows. Mixture of 438g (2.43mol) of 3-methyldiphenylamine and 49g (0.27mol) of 4-methyldiphenylamine whose mol ratio is 90: 10 were added to a 5000 ml four-necked flask made of glass. Further 28g (4.4mol) of powdered copper was added thereto. It was heated at 30 degrees Centigrade. 450g (1.1mol) of 4,4'-diiodobiphenyl and 47g of poly(ethylene glycol) PEG-6000 that was available from Wako Pure Chemical Industries, Ltd. were added thereto. It was heated at 100 degrees Centigrade, and then 307g (2.2mol) of powdered potassium carbonate was added thereto. It was heated at 205 degrees Centigrade, and stirred for 14 hours. After cooling, DMF was added thereto, and stirred at 130 degrees Centigrade for 1 hour. After cooling till 90 degrees Centigrade, hot water was added thereto. It was stirred for 2 hours. After filtration, filtrated cake was washed with hot water to obtain brown solid. The obtained brown solid was dispersed and stirred into DMF for 1 hour, filtrated and washed with DMF and methanol. The obtained solid was refluxed with activated carbon in xylene for 1 hour. After cooling till 70 degrees Centigrade, it was filtrated. The filtrate was passed through a column packing adsorbent to obtain colorless solution. The solvent was distilled under reduced pressure. Precipitated crystals were filtrated out and dried to obtain 455g of mixture of TPD. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; copper; In Soltrol/70; at 165℃; for 7h;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, and a condensing tube) was communicated with a nitrogen source and contained 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 168 g of potassium hydroxide (3 moles), 122 g of copper powder (1.76 moles) and 224 ml of Soltrol/70.(R). (fatty mixture of C13-C15 purchased from Phillips Chemical Company). The mixture solution was heated to 165° C. for 7 hours and then 2.5 L Soltrol/70.(R). was added. The temperature of the mixture solution was lowered to 154° C. to filter inorganic solids and to obtain a filtering liquid. 2 L of methanol was added to the filtering liquid to accelerate crystallization of the benzidine compounds. Then, the filtering liquid was filtered again to obtain a yellow solid, which is a crude mixture of three types of benzidine compounds. Moreover, 2 L of methanol dissolved the crude mixture of benzidine compounds and filtered by 1.2 Kg of Woelm neutral alumina to obtain a light-yellow solid. Lastly, n-octane was used to dissolve the light-yellow solid and to re-crystallize the benzidine compounds in the form of white crystal. The white crystal weighed 500 g, has a melting point range of 168-170° C., and is a final mixture of the benzidine compounds having high purity. | |
tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; at 139℃; for 6.5h;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, a condensing tube, and a Dean-Stark device) was communicated with a nitrogen source and accommodated 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 2.4 L of 10-crown-6-ether, 7.36 g of Pd2(dba)3 (0.008 mole) and 5.0 g 2,2'-bis(diphenylphosphino-1,1'-(binaphthyl) (0.008 mole). The mixture solution was stirred for 30 minutes and heated to a reflux temperature of 139° C. The mixture solution was further stirred to react for 6 hours and had further added thereto 1 L of m-xylene and 1 L of deionized water. The mixture solution was held at 65° C. and poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. an m-xylene solution, was removed from the mixture solution, washed with 2 L of deionized water twice and kept at 55° C. The m-xylene solution was filtered by 600 g of Woelm neutral alumina to obtain a filtering liquid. Then, the filtering liquid was dried to obtain 630 g of a crude mixture of benzidine compounds in the form of a yellow solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 595 g, has a melting point range of 169-170° C., and is a final mixture of the benzidine compounds having high purity. | |
With calcium carbonate; zinc;1,10-Phenanthroline; copper diacetate; In xylene; at 120℃; for 10.5h;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, and a condensing tube) was communicated with a nitrogen source and contained 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 2.4 L of xylene, 27 g of 1,10-phenanthroline (0.14 mole), 420 g of cuprous acetate-monohydrate (2.1 moles), 140 g of zinc (2.1 moles) and 552 g of calcium carbonate (4 moles). The mixture solution was stirred for 30 minutes and heated to 120° C. The mixture solution was further stirred to react for 10 hours and had further added thereto 500 ml of xylene, 500 ml of deionized water and 350 g of acetic acid to neutralize calcium carbonate. The mixture solution was held at 65° C. and poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. a xylene solution, was removed from the mixture solution, washed with 1.5 L of deionized water twice and kept at 55° C. The xylene solution was filtered by 500 g of Woelm neutral alumina to obtain a filtering liquid. Then, 1 L of methanol was added to the filtering liquid to accelerate crystallization of benzidine compounds to obtain 595 g crude mixture of benzidine compounds in the form of a white solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 545 g, has a melting point range of 169-170° C., and is a final mixture of the benzidine compounds having high purity |
With potassium hydroxide;1,10-Phenanthroline; copper dichloride; In toluene; at 125℃; for 6.5h;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, and a condensing tube) was communicated with a nitrogen source and contained 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 24 L of toluene, 27 g of 1,10-phenanthroline (0.14 mole), 16 g of cuprous chloride (0.14 mole) and 168 g potassium hydroxide (3 moles). The mixture solution was stirred for 30 minutes and heated to 125° C. The mixture solution was further stirred to react for 6 hours and had added thereto 500 ml of toluene, 500 ml of deionized water and 400 g of acetic acid to neutralize the potassium hydroxide. The mixture solution was held at 70° C. and then poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. a toluene solution, was removed from the mixture solution, washed with 1 L of deionized water twice and kept at 60° C. The toluene solution was filtered by 500 g of Woelm neutral alumina to obtain a filtering liquid. Then, the filtering liquid was dried to obtain 605 g of a crude mixture of benzidine compounds in the form of a white solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 500 g, has a melting point range of 169-170° C., and is a final mixture of the benzidine compounds having high purity. | |
With potassium hydroxide;1,10-Phenanthroline; copper dichloride; In m-xylene; at 139℃; for 7.5h;Heating / reflux;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, a condensing tube, and a Dean-Stark device) was communicated with a nitrogen source and accommodated 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 2.4 L of m-xylene, 27 g of 1,10-phenanthroline (0.14 mole), 16 g of cuprous chloride (0.14 mole) and 168 g potassium hydroxide (3 moles). The mixture solution was stirred for 30 minutes and heated to a reflux temperature of 139° C. The mixture solution was further stirred to react for 7 hours and had further added thereto 1 L of m-xylene, 1 L of deionized water and 400 g of acetic acid to neutralize the potassium hydroxide. The mixture solution was held at 65° C. and poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. an m-xylene solution, was removed from the mixture solution, washed with 2 L of deionized water twice and kept at 55° C. The m-xylene solution was filtered by 600 g of Woelm neutral alumina to obtain a filtering liquid. Then, the filtering liquid was dried to obtain 610 g of a crude mixture of benzidine compounds in the form of a Elite solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 585 g, has a melting point range of 169-170° C., and is a final mixture of the benzidine compounds having high purity. | |
With potassium hydroxide;1,10-Phenanthroline; copper dichloride; In xylene; at 145℃; for 7.5h;Heating / reflux;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, a condensing tube, and a Dean-Stark device) was communicated with a nitrogen source and accommodated 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 2.4 L of xylene, 27 g of 1,10-phenanthroline (0.14 mole), 16 g of cuprous chloride (0.14 mole) and 168 g of potassium hydroxide (3 moles). The mixture solution was stirred for 30 minutes and heated to a reflux temperature of 145° C. The mixture solution was further stirred to react for 7 hours and had further added thereto 1 L of o-xylene, 1 L of deionized water and 400 g of acetic acid to neutralize the potassium so hydroxide. The mixture solution was held at 100° C. and poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. an o-xylene solution, was removed from the mixture solution, washed with 1.5 L of deionized water twice and kept at 70° C. The o-xylene solution was filtered by 20 g of Alcoa-C neutral alumina to obtain a filtering liquid. Then, the filtering liquid was dried to obtain 615 g of a crude mixture of benzidine compounds in the form of a white solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 600 g, has a melting point range of 168-170° C., and is a final mixture of the benzidine compounds having high purity. | |
With potassium hydroxide; 18-crown-6 ether; copper; In m-xylene; at 139℃; for 10.5h;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, and a condensing tube) was communicated with a nitrogen source and contained 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 2.4 L of m-xylene (0.14 mole), 150 g of copper powder (2.4 moles), 168 g potassium hydroxide (3 moles) and 35 g of 18-crown-6-ether. The mixture solution was stirred for 30 minutes and heated to a reflux temperature of 139° C. The mixture solution was further stirred to react for 10 hours and had further added thereto 1 L of m-xylene, 1 L of deionized water and 400 g of acetic acid to neutralize the potassium hydroxide. The mixture solution was held at 65° C. and poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. an m-xylene solution, was removed from the mixture solution, washed with 2 L of deionized water twice and kept at 55° C. The m-xylene solution was filtered by 600 g of Woelm neutral alumina to obtain a filtering liquid. Then, the filtering liquid was dried to obtain 620 g of a crude mixture of benzidine compounds in the form of a white solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 600 g, has a melting point range of 169-170° C., and is a final mixture of the benzidine compounds having high purity. | |
With potassium hydroxide; copper; In Soltrol/170; at 190℃; for 10.5h;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, and a condensing tube) was communicated with a nitrogen source and accommodated 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 2 L of Soltrol.(R)./170, 150 g of copper powder (2.4 moles) and 168 g potassium hydroxide (3 moles). The mixture solution was stirred for 30 minutes and heated to 190° C. The mixture solution was further stirred to react for 10 hours and had further added thereto 1 L of toluene, 1.5 L of deionized water and 400 g of acetic acid to neutralize the potassium hydroxide. The mixture solution was held at 65° C. and poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. a toluene solution, was removed from the mixture solution, washed with 2 L of deionized water twice and kept at 55° C. The toluene solution was filtered by 500 g of Woelm neutral alumina to obtain a filtering liquid. Then, the filtering liquid was dried to obtain 630 g of a crude mixture of benzidine compounds in the form of a white solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 600 g, has a melting point range of 167-170° C., and is a final mixture of the benzidine compounds having high purity. | |
With sodium t-butanolate;palladium diacetate; tri-tert-butyl phosphine; In xylene; at 125℃; for 5.5h;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, a condensing tube, and a Dean-Stark device) was communicated with a nitrogen source and accommodated 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 2.5 L of xylene, 0.183 g of Pd(OAc)2 (0.051 mole), 0.14 g of P(t-Bu)3 (0.043 mole) and 350 g NaO-(t-Bu) (3.64 mole). The mixture solution was stirred for 30 minutes and heated to a reflux temperature of 125° C. The mixture solution was further stirred to react for 5 hours and had further added thereto 500 ml of o-xylene and 500 ml of deionized water. The mixture solution was held at 65° C. and poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. an o-xylene solution, was removed from the mixture solution, washed with 1 L of deionized water twice and kept at 55° C. The o-xylene solution was filtered by 500 g of Woelm neutral alumina to obtain a filtering liquid. Then, the filtering liquid was dried to obtain 660 g of a crude mixture of benzidine compounds in the form of a white solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 580 g, has a melting point range of 168-170° C., and is a final mixture of the benzidine compounds having high purity. | |
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 110℃; for 5.5h;Product distribution / selectivity; | A 5 L tri-neck round bottom flask (equipped with a mechanical stirrer, a thermal controller, a condensing tube, and a Dean-Stark device) was communicated with a nitrogen source and accommodated 500 g of dibromobiphenyl (1.6 moles), 620 g of 3-methyldiphenylamine (3.4 moles), 50 g of diphenylamine (0.3 mole), 2.4 L of toluene, 7.36 g of Pd2(dba)3 (0.008 mole) (prepared according to J. Org. Chem. 2000,65,p.5330) and 350 g NaO-(t-Bu) (3.64 mole). The mixture solution was stirred for 30 minutes and heated to a reflux temperature of 110° C. The mixture solution was further stirred to react for 5 hours and had further added thereto 500 ml of toluene and 500 ml of deionized water. The mixture solution was held at 55° C. and poured into an extracting bottle to place for 10 minutes until layers of the mixture solution separated. An organic layer, i.e. a toluene solution, was removed from the mixture solution, washed with 2 L of deionized water twice and kept at 55° C. The toluene solution was filtered by using 500 g of Woelm neutral alumina to obtain a filtering liquid. Then, the filtering liquid was dried to obtain 650 g of a crude mixture of benzidine compounds in the form of a yellow solid. Lastly, n-octane was used to dissolve the crude mixture and to re-crystallize the benzidine compounds in the form of pure white crystal. The pure white crystal weighed 550 g, has a melting point range of 169-170° C., and is a final mixture of the benzidine compounds having high purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.2% | With tetrabutyl phosphonium bromide; potassium carbonate;copper(l) chloride; In toluene; at 200 - 210℃; for 10h;Product distribution / selectivity; | Examples 2 to 8; Synthesis was conducted in the same manner as in Example 1, except that the aromatic halogen compound, organic salt, and base used in Example 1 were replaced by those shown in Table 1 and the reaction temperature was changed. The results obtained are shown in Table 1. |
94.0% | With potassium hydroxide; tetrabutyl phosphonium bromide;copper(l) chloride; In toluene; at 115 - 125℃; for 1h;Product distribution / selectivity; | Example 1; Synthesis of N,N'-Diphenyl-N,N'-bis(3-methylphenyl)(p-terphenyl)-4,4-di amine (exemplified compound I-11); N-(3-Methylphenyl)-N-phenylamine was mixed in an amount of 18.05 g (98.52 mmol) with 11.87 g (24.63 mmol) of 4,4-diiodo-1,1':4',1-terphenyl, 11.06 g (197.0 mmol) of potassium hydroxide, 0.4 g (4.0 mmol) of copper (I) chloride, 1.36 g (4.0 mmol) of tetra-n-butylphosphonium bromide, and 10 mL of toluene. This mixture was reacted at 115-125 C. for 1 hour in a nitrogen stream. After the reaction, 25 mL of toluene and 50 mL of water were added and the resultant mixture was subjected to liquid separation. Thereafter, the organic layer was washed with water and dehydrated and dried with anhydrous sodium sulfate. After the drying agent was removed by filtration, 3.9 g of activated clay was added. The resultant mixture was stirred at 50-55 C. for 1 hour and the clay was removed by filtration. The toluene was distilled off under reduced pressure and 28 mL of ethyl acetate was added to the residue. The resultant solution was cooled for crystallization, and the precipitate was taken out by filtration. Thus, the target compound (I-11) was obtained as white crude crystals in an amount of 13.7 g (yield, 94.0%). The target compound obtained had a melting point of 189-190 C. and a content as determined by HPLC of 99.5% (HPLC conditions: column, YMC-A-002; eluent, hexane/tetrahydrofuran (V/V=97/3); detection UV, 310 nm; flow rate, 0.8 mL/min). |
94.2% | With potassium hydroxide; triphenylmethylarsonium iodide;copper(l) chloride; In toluene; at 115 - 125℃; for 1h;Product distribution / selectivity; | Examples 2 to 8; Synthesis was conducted in the same manner as in Example 1, except that the aromatic halogen compound, organic salt, and base used in Example 1 were replaced by those shown in Table 1 and the reaction temperature was changed. The results obtained are shown in Table 1. |
92.0% | With potassium hydroxide; tetraphenylstibonium bromide;copper(l) chloride; In toluene; at 115 - 125℃; for 1.5h;Product distribution / selectivity; | Examples 2 to 8; Synthesis was conducted in the same manner as in Example 1, except that the aromatic halogen compound, organic salt, and base used in Example 1 were replaced by those shown in Table 1 and the reaction temperature was changed. The results obtained are shown in Table 1. |
89.2% | With potassium hydroxide;copper(l) chloride; In toluene; at 240 - 250℃; for 7h;Product distribution / selectivity; | Comparative Examples 1 and 2; Synthesis was conducted in the same manner as in Example 1, except that no organic salt was used and the reaction temperature was changed to the temperature shown in Table 1. The results obtained are shown in Table 1. |
88.0% | With potassium hydroxide; N-benzyl-N,N,N-triethylammonium chloride;copper(l) chloride; In toluene; at 115 - 125℃; for 3h;Product distribution / selectivity; | Examples 2 to 8; Synthesis was conducted in the same manner as in Example 1, except that the aromatic halogen compound, organic salt, and base used in Example 1 were replaced by those shown in Table 1 and the reaction temperature was changed. The results obtained are shown in Table 1. |
84.6% | With potassium hydroxide; n-butylpyridinium chloride;copper(l) chloride; In toluene; at 115 - 125℃; for 3h;Product distribution / selectivity; | Examples 2 to 8; Synthesis was conducted in the same manner as in Example 1, except that the aromatic halogen compound, organic salt, and base used in Example 1 were replaced by those shown in Table 1 and the reaction temperature was changed. The results obtained are shown in Table 1. |
77.6% | With potassium hydroxide; 1-ethyl-3-methyl-1H-imidazol-3-ium chloride;copper(l) chloride; In toluene; at 115 - 125℃; for 2h;Product distribution / selectivity; | Examples 2 to 8; Synthesis was conducted in the same manner as in Example 1, except that the aromatic halogen compound, organic salt, and base used in Example 1 were replaced by those shown in Table 1 and the reaction temperature was changed. The results obtained are shown in Table 1. |
With potassium carbonate;copper(l) chloride; In toluene; at 200 - 210℃;Reactivity (does not react); | Comparative Example 3; Synthesis was conducted in the same manner as in Example 1, except that the same aromatic halogen compound and base as in Example 8 were used and no organic salt was used. The results obtained are shown in Table 1. | |
With potassium hydroxide;copper(l) chloride; In toluene; at 115 - 125℃; for 30h;Reactivity (does not react); | Comparative Examples 1 and 2; Synthesis was conducted in the same manner as in Example 1, except that no organic salt was used and the reaction temperature was changed to the temperature shown in Table 1. The results obtained are shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
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With pyridine;AlCl3; In dichloromethane; | (a) 2',3',6'-Trifluorophenyl 1,10-dimethylacridan-9-carboxylate. Reaction of 3-methyldiphenylamine (Aldrich) with AlCl3 and oxalyl chloride followed by base-catalyzed rearrangement of the isatins produced a mixture of 1-methylacridine-9-carboxylic acid and 3-methylacridine-9-carboxylic acid. The mixed acids (4 g, 15.6 mmol) were suspended in excess SOCl2 (50 mL) and the reaction mixture was refluxed for 1.5 h. The solvent was removed under reduced pressure. To the above residue was added <strong>[113798-74-6]2,3,6-trifluorophenol</strong> (2.77 g, 18.7 mmol). This mixture was dissolved in CH2 Cl2 and pyridine (4 ml, 49.5 mmol) was added dropwise under argon. The solution was stirred for several days at room temperature, then the solvent and excess pyridine were removed under reduced pressure. The crude material obtained was chromatographed on silica gel (5% ethyl acetate/hexane) to yield 1-methylacridan ester 3 g and the isomeric 3-methyl ester. Compound 3 g: 1 H NMR (CDCl3) delta 7.04-7.25 (m, 2H), 7.70-7.77 (m, 3H), 7.87-7.92 (t, 1H), 8.24-8.31 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
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With potassium hydroxide; | EXAMPLE V Preparation of N,N'-diphenyl-N,N'-bis-(3-methylphenyl)-[1,1'-biphenyl]-4,4'-diamine in the absence of the aliphatic hydrocarbon solvent. A 500 milliliter 3 necked round bottom flask equipped with an argon purge, a condenser and an overhead mechanical stirrer was charged with 81.2 grams (0.2 mole) of 4,4'-diiodobiphenyl, 146.4 grams (0.8 mole) of 3-methyl-diphenylamine, 89.6 grams (1.6 moles) of KOH flake and 80 grams (1.0 mole) of copper powder. The flask was immersed in a 165° C. oil bath and the two-phase melt was stirred for 3 hours. Hot (140° C.) Soltrol.(R). 170 was added and the inorganic solid separated by vacuum filtration. On cooling, the product crystallized from the filtrate and was isolated in 89percent yield by filtration. Purification was accomplished by slurrying the product with neutral alumina (10 grams) in 1 liter of Soltrol.(R). 170 at 150° C. for six hours, the alumina was removed by filtration and the purified product crystallized from the filtration on cooling. Isolation by filtration was accomplished with a 95percent recovery of the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | VIII Preparation of 3-methylphenyldiphenylamine EXAMPLE VIII Preparation of 3-methylphenyldiphenylamine The same equipment and conditions as in example I were employed with the following charge: 20.4 grams (0.1 mole) iodobenzene, 27.5 grams (0.15 mole) 3-methyldiphenylamine, 15.0 grams copper powder and 30.0 milliliters of Soltrol 170. The above-identified intended product was obtained as colorless crystals having a melting point of 69°-70° C. Yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
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74% | With sodium t-butanolate;tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); In toluene; for 2h;Heating / reflux; | The compound of Formula a (1.3 g, 2.2 mmol), 3-tolylphenylamine (0.87 mL, 5.1 mmol), sodium t-butoxide (0.63 g, 6.6 mmol), Pd(dba) (0.06 g, 0.1 mmol) and P(t-Bu)(0.03 g, 0.1 mmol) were added to toluene (20 mL), and then was refluxed under stirring for about 2 hours. After completing the reaction, the mixture was cooled to room temperature and added to a mixed solution of THF and H O. The organic layer was separated from the mixture, dried over MgSO and concentrated. The residue was purified by column chromatography, and then recrystallized from dichloromethane and <n="41"/>ethanol to obtain a compound of Formula 2-3 (1.3 g, 74%). [170] 1U NMR (400 MHz, DMSO-J ) 7.71-7.69(q, 2H), 7.56-7.54(q, 2H), 7.29-7.25(t,4H), 7.18-7.15(t, 2H), 7.10-7.08(d, 4H), 7.02-6.98(t, 2H), 6.96-6.95(m, 6H),6.91-6.88(m, 8H), 6.85-6.82(m, 6H), 6.72-6.70(d, 4H), 2.22 (s, 6H); MS [M+H] 795 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With sodium t-butanolate;tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); In toluene; for 2h;Heating / reflux; | Formula b (1.5 g, 2.54 mmol), 3-tolylphenylamine (1.01 mL, 5.1 mmol), sodium t- butoxide (0.73 g, 5.8 mmol), Pd(dba) (0.07 g, 0.13 mmol) and P(f-Bu) (0.03 g, 0.13 mmol) were added to toluene (25 mL), and then was refluxed under stirring for about 2 hours. After completing the reaction, the mixture was cooled to room temperature and added to a mixed solution of THF and H O. The organic layer was separated from the mixture, dried over MgSO and concentrated. The residue was purified by column4 chromatography, and then recrystallized from dichloromethane and ethanol to obtain a compound of Formula 2-7 (0.72 g, 36%). [185] 1U NMR (400 MHz, DMSO-J ) 7.94-7.92(d, 2H), 7.81-7.79(d, 2H), 7.60-7.58(d,2H), 7.52-7.49(q, 2H), 7.45-7.40(m, 6H), 7.33-7.30(m, 6H), 7.23-7.12(m, 10H),7.08-7.06(d, 2H), 6.91-6.87(t, 2H), 6.72-6.65(dd, 8H), 6.52-6.49(d, 4H), 2.11 (s, 6H);MS [M+H] 795 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With NHC-Pd(II)-Im; potassium tert-butylate; In toluene; for 4h;Inert atmosphere; Reflux; | General procedure: Under N2 atmosphere, KOtBu (114.0 mg, 1.0 mmol), NHC-Pd(II)-Im complex 1 (5.2 mg, 1.0 mol %), dry toluene (1.0 mL), chlorobenzene 2a (0.8 mmol), and aniline 3a (0.96 mmol) were successively added into a Schlenk reaction tube. The reaction mixture was stirred under reflux for 4 h. Then the solvent was removed under reduced pressure and the residue was purified by a flash chromatography on silica gel to give the pure product 4a. |
94% | With C19H14N4NiO2; potassium tert-butylate; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere; Schlenk technique; | General procedure: Under an N2atmosphere, KOtBu (1.3 mmol), complex 1 (1 mol%),dioxane (2 ml), amines (1.3 mmol) and aryl chlorides (1.0 mmol)were successively added into a Schlenk tube. The mixture wasstirred vigorously at 90C for 4 h. Then the solvent was removedunder reduced pressure and the residue was purified by columnchromatography on silica gel (eluent:PE/EA = 15:1) to give the pureproducts. The reported yields are the average of two runs.The catalytic reactions have been given in Tables 4-7. The result-ing amines were identified by comparison of the1H and13C NMRdata with those previously reported (ESI). |
93% | With bis{1,1?-diphenyl-3,3?-methylenediimidazoline-2,2?-diylidene}nickel(II) dibromide; potassium tert-butylate; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere; Schlenk technique;Catalytic behavior; | General procedure: Under an N2 atmosphere, KOtBu (1.3 mmol), complex 1 (1 mol %), dioxane (2 ml), amines (1.3 mmol) and aryl chlorides (1.0 mmol) were successively added into a Schlenk tube. The mixture was stirred vigorously at 90 C for 4 h. Then the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (eluent: PE/EA = 15:1) to give the pure products. The reported yields are the average of two runs. |
43% | With C28H29Cl2N3OPd; potassium tert-butylate; In toluene; at 110℃; for 15h;Schlenk technique; Inert atmosphere; | General procedure: A Schlenk ask was charged with the required aryl chloride (0.25 mmol), amine (0.30 mmol), N-heterocyclic carbene-palladium(II) complex (2 mol%), KOtBu (1.3 equiv), and toluene (0.5 mL). The mixture was stirred at 110 C for 15 h under N2. After cooling, the mixture was evaporated and the product was isolated by preparative TLC on silica gel plates. The puried products were identied by 1H NMR spectra, and their analytical data are given in the Supporting Information. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine; In N,N-dimethyl-formamide; at 60℃; for 2h;Catalytic behavior; | General procedure: In a 50 cm3 round-bottom flask, phenylboronic acid(1.2 mmol), primary amine (1.0 mmol), triethyl amine(2.0 mmol), and 80 mg (0.018 mol% of Cu) Cu-ACP-Am-Fe3O4SiO2 were mixed in 5 cm3 DMF and the reactionwas allowed to stir at 60 C temperature for 2 h in aerobiccondition. Reactions was monitored by thin-layer chromatography(TLC) using aluminum-backed silica gel 60 (F254)plates. After completion of the reaction, the catalyst wasseparated magnetically using bar magnet. Finally, the resultingsolution was extracted with ethyl acetate and dried overanhydrous Na2SO4.The solvent was removed under reducedpressure and the product was purified by silica gel columnchromatography. |
84% | With triethylamine; In methanol; at 20℃; for 5h; | General procedure: In a typical reaction, arylboronic acid (1 mmol), amino-compound (1 mmol), catalyst (5 wt%), Et3N (2 mmol) were mixed in methanol ( 5mL) in a 25mL round bottomed flask. The reaction mixture was subjected under continuous stirring at room temperature for 5 h. Reaction was monitored from time to time using TLC. After completion of the reaction, catalyst was separated with the aid of an external magnet and reaction mixture was taken in ethyl acetate. The organiclayer was washed using brine solution, dried over sodium sulfate. After evaporating the solvent, the crude product was puried by column chromatography using 230-400 silica mesh. The recovered catalyst was washed with methanol and ethyl acetate, dried in oven and kept in desiccator for further use. |
78% | With potassium carbonate; In acetonitrile; for 13h;Reflux; | General procedure: Aniline (0.0931g, 1mmol) and phenylboronic acid (0.2438g, 2mmol) were dissolved in acetonitrile (10mL) in a50mL round bottomed flask and stirred for 20 minutes. The base K2CO3(0.2764g, 2mmol) and complex (C3) (8 mol%) were added to thereaction flask. The mixture washeated under reflux for specific time (9-12 hr). The progress of the reactionwas monitored by TLC at regular intervals. After completion, the reactionmixture was cooled to room temperature and the catalyst was removed byfiltration. The filtrate was treated with ethyl acetate (3x10mL). The combinedorganic layers were treated with saturated brine solution and dried overanhydrous sodium sulphate. The removal of solvent yields crude product, whichafter purification by column chromatographyover Silica gel G-60, afforded the desired product. The spectral data ofsynthesized product are given below. |
75% | With C21H16CuN2O2; potassium carbonate; In water; at 28℃; for 19h; | General procedure: A 50 mL round bottomed flask was charged with amine (0.5 mmol), arylboronicacid (0.75 mmol), K2CO3 (1.5 mmol, 207 mg), C-1 complex (20 mol %, 39.15 mg) in 3 mL of water at room temperature. The reaction mixture was stirred with a magnetic stirrer for appropriate time. The progress of the reaction was monitored by TLC. After the completion of the reaction, the mixture was diluted with 20 mL of water and extracted with diethylether (3*20 mL). The combined organic layer were washed with brine and dried over by anhydrous Na2SO4 and evaporated in a rotary evaporator under reduced pressure. The crude was purified by column chromatography on silica gel (hexane/ethyl acetate, 9:1) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In dichloromethane; at 20℃; for 6h;Molecular sieve; | General procedure: To a solution of compound 2(0.108 g, 0.5 mmol) in solvent (8 mL) was added amine (0.6 mmol) and 4A molecule sieve (4 g). The mixture was stirred at room temperature, tracked byTLC. After compound 2 disappeared, the mixture was filtered and the filtrate was concentrated, the products were obtained by flash chromatography using petroleum ether and ethyl acetate (5/1 to 3/1, V/V) as eluent. All the productshave been previously reported in references and were conformed by comparing melting points and 1H NMR or MS data and spectra with literatures. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With C21H16CuN2O2; potassium carbonate; In water; at 28℃; for 22h; | General procedure: A 50 mL round bottomed flask was charged with amine (0.5 mmol), arylboronicacid (0.75 mmol), K2CO3 (1.5 mmol, 207 mg), C-1 complex (20 mol %, 39.15 mg) in 3 mL of water at room temperature. The reaction mixture was stirred with a magnetic stirrer for appropriate time. The progress of the reaction was monitored by TLC. After the completion of the reaction, the mixture was diluted with 20 mL of water and extracted with diethylether (3*20 mL). The combined organic layer were washed with brine and dried over by anhydrous Na2SO4 and evaporated in a rotary evaporator under reduced pressure. The crude was purified by column chromatography on silica gel (hexane/ethyl acetate, 9:1) to afford the desired product. |
78% | With N-(pyrid-2-yl)benzamide; nickel(II) acetate tetrahydrate; N,N,N',N'-tetramethylguanidine; In toluene; at 60℃; for 24h; | General procedure: The 25 mL RB flask was charged with arylboronic acid (1 mmol), N-nucleophile (2 mmol), Ni(OAc)2*4H2O/1a (10 mol % of Ni(II) salt and 20 mol % of 1a), TMG (2 mmol), and toluene (1 ml). The reaction mixture was stirred at 60 C for 24 h. After completion of the reaction, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (20 mL), and washed with brine water. The combined organic phase was dried over anhydrous Na2SO4. After removal of the solvent, the residue was subjected to column chromatography on silica gel using hexane to afford the Chan-Lam product in high purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100℃; for 12h;Inert atmosphere; | General procedure: General procedure for the palladium-catalyzed reaction A solution of Pd(OAc)2 (0.8 mg, 0.0036 mmol), Xantphos (2.1 mg, 0.0036 mmol), NaOtBu (51 mg, 0.53 mmol), 1-bromo-4-iodobenzene (1a) (100 mg, 0.35 mmol), and N,N-diphenylamine (2a) (72 mg, 0.43 mmol) in toluene (0.5 mL) was stirred at 100 C for 12 h. The reaction was quenched with H2O, and extracted with CH2Cl2 (3*3 mL). The chemoselectivity (3aa/4aa=92/8) was measured by HPLC analysis using Inertsil ODS-3V. The pure monoaminated product 3aa (99 mg, 86%) was obtained by flash chromatography (hexane/CH2Cl2=97/3) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With iron(II) phthalocyanine; copper diacetate; In ethanol; at 40℃; | A reaction flask was added 3-methylaniline 0.107 g (1 mmol), phenylhydrazine 0.216g (2 mmol), FePc 0.114 Ke (0.2 mmol), Cu (OAc) 2 0.03 g (0.15 mmol) and 10 ml of ethanol 40 C reaction; TLC until complete reaction was followed over; After the reaction, thecrude product obtained was purified by column chromatography (petroleum ether: ethylacetate = 100: 1) to give the desired product (86% yield). |
76% | With tetrabenzoporphyrinatocobalt(II); copper diacetate; In acetonitrile; at 0℃; for 13h; | General procedure: Into a 25 mL round-bottom flask, amine (2) (1 mmol), Cu(OAc)2 (0.02 g, 0.1 mmol) and acetonitrile (4 mL) were added, the mixture was stirred and cooled to 0 C. Then, CoPc (0.057 g, 0.1 mmol) was added, the solution of arylhydrazine (1) (2 mmol) in acetonitrile (2 mL) was added successively at a rate of 0.2 mmol per hour while stirring for 13 h in air. After completion of the reaction monitored by TLC analysis (developing solvent: ethyl acetate/petroleum ether (1:8)), the mixture was filtered, concentrated, and the residue was further purified by column chromatography using ethyl acetate/petroleum ether (1:100) as eluent to afford N-aryl amine 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With cobalt(II) phthalocyanine; copper(l) chloride; In chloroform; at 20℃; | In the reaction flask aniline 0.093 g (1 mmol), 3- methyl phenylhydrazine 0.159 g(1.3 mmol), CoPc 0.057 g (0.1 mmol), CuCl0.01 g (0.1 mmol) and 10 ml of chloroform, 20 C reaction ; TLC until complete reaction was followed over; after the reaction, thecrude product obtained was purified by column chromatography (petroleum ether: ethylacetate = 100: 1) to give the desired product (yield 85%). |
75% | With tetrabenzoporphyrinatocobalt(II); copper diacetate; In acetonitrile; at 0℃; for 13h; | General procedure: Into a 25 mL round-bottom flask, amine (2) (1 mmol), Cu(OAc)2 (0.02 g, 0.1 mmol) and acetonitrile (4 mL) were added, the mixture was stirred and cooled to 0 C. Then, CoPc (0.057 g, 0.1 mmol) was added, the solution of arylhydrazine (1) (2 mmol) in acetonitrile (2 mL) was added successively at a rate of 0.2 mmol per hour while stirring for 13 h in air. After completion of the reaction monitored by TLC analysis (developing solvent: ethyl acetate/petroleum ether (1:8)), the mixture was filtered, concentrated, and the residue was further purified by column chromatography using ethyl acetate/petroleum ether (1:100) as eluent to afford N-aryl amine 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; for 4h;Reflux; Inert atmosphere; | In the round bottom flask was charged with 1,3-dibromo-5-chlorobenzene 25g (92.47mmol) and methyl diphenyl amine 33.9g (184.9mmol) into a sodium t- butoxide 26.7g (277.41mmol) was added to 463ml toluene dissolved. Here Pd (dba)2 0.266g (0.462mmol) and tri-tert-butylphosphine was put 0.187g (0.924mmol) in turn and the mixture was stirred under reflux for 4 hours under a nitrogen atmosphere. After the reaction the organic layer was then extracted with ethyl acetate dry distilled over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product n- hexane / dichloromethane (9: 1 by volume) to yield the silica gel column 37.3g (yield 85%) of intermediate M-11 the desired compound is purified by chromatography as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With tri-tert-butyl phosphine; 5%-palladium/activated carbon; sodium t-butanolate; In o-xylene; at 110℃; for 2h;Inert atmosphere; | A cooling tube, round bottom flask 50mL equipped with athermometer, at room temperature, bromobenzene 1.4g in a nitrogen atmosphere(9.0 mmol), 3- methyl-diphenylamine 1.1 g (6.0 mmol), palladium supported materialB 0 .13g (palladium atom 0.12mmol), was mixed with sodium -tert- butoxide 0.86g(9.0mmol) and o- xylene 6.0g. After nitrogen is a flow of about 20 minutes, tri(tert- butyl) phosphine (hereinafter, "P- (tBu) 3" and also indicate)36.4 mg (0.18 mmol) was dissolved o- xylene ( 150 uL) was added and undernormal pressure, pressurized to 110 C.It was raised and the mixture was stirred for 2 hours after.Incidentally, the yield by gas chromatography, was calculated by internalstandard method with an internal standard substance n- eicosane. The resultsare shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With tri-tert-butyl phosphine; 5%-palladium/activated carbon; sodium t-butanolate; In o-xylene; at 110℃; for 2h;Inert atmosphere; | General procedure: A cooling tube, round bottom flask 50mL equipped with athermometer, at room temperature, bromobenzene 1.4g in a nitrogen atmosphere(9.0 mmol), 3- methyl-diphenylamine 1.1 g (6.0 mmol), palladium supported materialB 0 .13g (palladium atom 0.12mmol), was mixed with sodium -tert- butoxide 0.86g(9.0mmol) and o- xylene 6.0g. After nitrogen is a flow of about 20 minutes, tri(tert- butyl) phosphine (hereinafter, "P- (tBu) 3" and also indicate)36.4 mg (0.18 mmol) was dissolved o- xylene ( 150 uL) was added and undernormal pressure, pressurized to 110 C.It was raised and the mixture was stirred for 2 hours after.Incidentally, the yield by gas chromatography, was calculated by internalstandard method with an internal standard substance n- eicosane. The resultsare shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium acetate; palladium diacetate; triphenylphosphine; In toluene; at 100℃; for 12h;Schlenk technique; Inert atmosphere; | General procedure: A Schlenk reaction tube was charged with Amine or amide 1 (1.2 mmol), aryltrimethylgermane 2 (1.0 mmol), Pd(OAc)2 (5 mol %), PPh3 (5 mol %), toluene (2.0 mL), under argon atmosphere at 100 C for 12 h. After completion of the reaction, asindicated by TLC, the reaction mixture was extracted with diethyl ether (3×10 mL). The combined organic layer was washedby water and dried by Na2SO4. The solvent was removed in vacuo and the residue, further purification was carried out byshort column chromatography (silica gel 300400 mesh, petroleum ether / ethyl acetate as the eluent) to give the targetmolecules. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71 %Chromat. | With gold-palladium bimetallic nanoparticles supported on TiO2 In 1,3,5-trimethyl-benzene at 160℃; for 24h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With bis-[(trifluoroacetoxy)iodo]benzene; In 1,2-dichloro-ethane; at 20℃; for 0.5h; | General procedure: PIFA (0.75 equiv.) was added to a stirred solution of the appropriatenaphthalenamine 1 (0.30 mmol, 1 equiv) in DCE (3 mL) atr.t., and the mixture was stirred for 30 min. When the reactionwas complete, sat. aq NaHCO3 was added to the mixture, andthe aqueous phase was extracted with CH2Cl2. The extractswere dried (Na2SO4) and evaporated to dryness, and the cruderesidue was purified by column chromatography (silica gel,hexane-EtOAc). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 68% 2: 18% | Stage #1: Diphenyliodonium triflate; 1-amino-3-methylbenzene With copper(l) iodide; 2,6-di-tert-butyl-pyridine In toluene at 20℃; for 12h; Schlenk technique; Inert atmosphere; Stage #2: With copper(l) iodide; 1,10-Phenanthroline; potassium <i>tert</i>-butylate In toluene at 120℃; for 24h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene; at 110℃; for 24h;Molecular sieve; Inert atmosphere; Schlenk technique; | General procedure: To a mixture of PhN=NNHTs (1 mmol), boronic acid (1.5 mmol) 4 A MS (0.25 g) and freshly distilled DBU (3 mmol), dry toluene (2 mL) was added in a Schlenk flask under nitrogen atmosphere. The tube was caped tightly and heated at 110 C for 24 h. After completion of reaction, water was added to the reaction mixture and extracted with EtOAc. The EtOAc layer was separated, washed with brine, dried over Na2SO4, and evaporated. Purification of the crude product by flash chromatography over silica gel (230-400 mesh) with petroleum ether-EtOAc as eluent gave the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With potassium phosphate; In toluene; at 80℃; for 15h;Inert atmosphere; | General procedure: To a 50 mL of two-neck round-bottomed flask charged with a magnetic stirrer bar, were successively added 1-Bromo(2-diphenylphosphoryl)ethyne (1) (305 mg, 1.0 mmol), diphenylamine(203 mg, 1.2 mmol, 1.2 equiv), K3PO4 (637 mg, 3.0 mmol, 3.0 equiv) and dehydrated toluene (5mL). After the mixture was stirred at 80 C for 15 h, the reaction mixture was quenched with 1 mL of saturated NH4Cl aq., and extracted with ethyl acetate and H2O, and dried over brine and MgSO4. The crude product was purified by flash chromatography (hexane/EtOAc, 1:2) to afford the corresponding phosphoryl ynamine 2a (240 mg) in 61% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.9% | With tri-tert-butyl phosphine; palladium diacetate; caesium carbonate; In toluene; at 110℃; for 20h;Inert atmosphere; | Under a nitrogen atmosphere,Adding 2,2'-dibromo-9,9'-spirobifluorene (0.7 g, 1.48 mmol),3-methyldiphenylamine (0.82 g, 4.44 mmol),Palladium acetate (18mg, 0.082mmol),Cesium carbonate (1.74g, 5.33mmol)And tri-tert-butylphosphine (0.038mL, 0.15mmol) in toluene (10mL)Heat and stir at 110 C for 20 hours.After cooling to room temperature,The reaction was quenched with a saturated ammonium chloride solution.The aqueous layer was extracted three times with ethyl acetate,The combined organic phases were washed with a saturated aqueous sodium chloride solution.After the organic phase was dried over anhydrous sodium sulfate,The solvent was evaporated to dryness under reduced pressure,The obtained product was further purified by silica gel column chromatography,Petroleum ether / ethyl acetate (10: 1, v / v) was used as the eluent.Get pure product,As a white solid.Yield: 82.9% (0.8 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With palladium on activated charcoal; toluene-4-sulfonic acid In 1,3,5-trimethyl-benzene at 160℃; for 2h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With palladium on activated charcoal; toluene-4-sulfonic acid In 1,3,5-trimethyl-benzene at 160℃; for 18h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With palladium on activated charcoal; toluene-4-sulfonic acid In 1,3,5-trimethyl-benzene at 160℃; for 2h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With palladium on activated charcoal; toluene-4-sulfonic acid In 1,3,5-trimethyl-benzene at 160℃; for 2h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With palladium on activated charcoal; toluene-4-sulfonic acid In 1,3,5-trimethyl-benzene at 160℃; for 2h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.29% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In toluene at 90℃; for 5h; Inert atmosphere; | 3.3 Step 3. Under the protection of nitrogen,Intermediate 2 (17.00g, 21.37mmol) and raw material D-052 (3.92g, 21.37mmol) were dissolved in 200.00ml of toluene solution,Add tris(dibenzylideneacetone)dipalladium (0.19g, 0.21mmol),Tri-tert-butylphosphine (0.22g, 1.07mmol) and sodium tert-butoxide (4.11g, 42.74mmol),Stir evenly, heat up to 90, and reflux for 5h;After the reaction, the temperature was slightly reduced to 70°C, and then filtered with diatomaceous earth.After removing the salt and catalyst, the filtrate is cooled to room temperature,Wash with water three times, keep the organic phase, and then extract the aqueous phase with ethyl acetate;After combining the organic phases, use anhydrous magnesium sulfate for drying,Dissolve the solid organic matter in the toluene solution and stir at the temperature for 5 hours.After the solution is cooled to room temperature, the solution is suction filtered to obtain a solid,Then it was rinsed with petroleum ether and dried to obtain Intermediate 3 (16.56g, yield: 86.29%); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 110℃; for 24h;Inert atmosphere; Schlenk technique; | Add <strong>[25032-74-0]bis(3-bromophenyl)methanone</strong> (1.35g, 3.75mmol), 3-methyl-N-phenylaniline (1.5g, 8.25mmol, purchased from Adamas), and tri-tert-butylPhosphine (30mg, 0.15mmol), into a 100mL Schlenk flask. Pd2(dba )3 (137mg, 0.15mmol), sodium tert-butoxide (828mg, 8.625mmol) and toluene (20mL), the reaction system was heated to 110C under a nitrogen atmosphere and stirred for 24 Hour.After cooling to room temperature, adding H2O and EA for extraction, the organic phases were combined, dried with anhydrous Na2SO4, and the solvent was removed by a rotary evaporator to obtain a crude product.The crude product was purified by column chromatography (silica gel column, eluent: PE:EA=100:1, volume ratio) to obtain a pale yellow solid as the product with a yield of 88%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; at 110℃; for 24h;Inert atmosphere; Schlenk technique; | To a 100mL Schlenk flask add <strong>[25032-74-0]bis(3-bromophenyl)methanone</strong> (1.35g, 3.75mmol), 3-methyl-N-phenylaniline (458g, 2.5mmol, purchased from Adamas), and tri-tert-butylphosphine (30mg, 0.15mmol), into a 100mL schlenk flask. Pd2(dba)3(137mg, 0.15mmol), sodium tert-butoxide (720mg, 7.5mmol) and toluene (20mL), the reaction system was heated to 110C in a nitrogen atmosphere and stirred for 24 hours .After cooling to room temperature, adding H2O and EA for extraction, the organic phases were combined, dried over anhydrous Na2SO4, and the solvent was removed by a rotary evaporator to obtain a crude product.The crude product was purified by column chromatography (silica gel column, eluent PE:EA=100:1, volume ratio) to obtain a pale yellow solid as the product with a yield of 76%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.6% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In toluene at 110℃; for 24h; Schlenk technique; Inert atmosphere; | 2.1 (1) Synthesis of 2,7-bis(phenyl(m-tolyl)amino)-9H-fluorenone Add 2,7-dibromo-9-fluorenone (1g, 3mmol, purchased from Adamas) and 3-methyl-N-phenylaniline (1.2g, 6.6mmol, purchased from Adamas) into a 100mL schlenk tube , Pd2(dba)3(100mg, 0.12mmol), tri-tert-butylphosphine (24mg, 0.12mmol), sodium tert-butoxide (663mg, 6.9mmol) and toluene (20mL), the reaction system is heated to Stir at 110°C for 24 hours in a nitrogen environment. After cooling to room temperature, adding H2O and EA for extraction, the organic phases were combined, dried with anhydrous Na2SO4, and the solvent was removed by a rotary evaporator to obtain a crude product.The crude product was purified by column chromatography (silica gel column, eluent PE:EA=50:1, volume ratio) to obtain a purple solid as the product with a yield of 92.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In toluene at 110℃; for 24h; Inert atmosphere; Schlenk technique; | 5.1 (1) Synthesis of 2-bromo-7-(phenyl(m-tolyl)amino)-9H-fluorenone Add 2,7-dibromo-9-fluorenone (1g, 3mmol, purchased from Adamas) into a 100mL Schlenk tube, 3-methyl-N-phenylaniline (367mg, 2mmol, purchased from Adamas), and Pd to a 100mL schlenk tube.2(dba)3(192mg, 0.1mmol), tri-tert-butylphosphine (10mg, 0.1mmol), sodium tert-butoxide (576mg, 6mmol) and toluene (20mL), the reaction system was heated to 110°C under a nitrogen atmosphere and stirred 24 hours.After cooling to room temperature, adding H2O and EA for extraction, the organic phases were combined, dried with anhydrous Na2SO4, and the solvent was removed by a rotary evaporator to obtain a crude product.The crude product was purified by column chromatography (silica gel column, eluent PE:EA=50:1, volume ratio) to obtain a rose-red solid as the product with a yield of 84%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 93% 2: 7% | With iron(III) trichloride hexahydrate; triphenylphosphine; sodium hydroxide In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 20℃; for 0.75h; Sonication; Green chemistry; | Method C: General procedure: The ultrasonic probe was immersed directlyin the reactor. An ultrasonic generator (Sonics VC 505 300W) emitted sound vibration into the reaction mixture. Sonificationwas achieved at a low frequency of 20 kHz (50% amplitude) at room temperature for 45 min. The aryl halideor arylboronic acids (4.5 mmol), the aniline compound (2.25mmol), the ligand (0.05 mmol) and the catalyst FeCl3.6H2O,Ag, CuO or ZrO2) (0.025 mmol) were placed in a reactor. 3mL of solvent were added. After the reaction, the mixturewas extracted (three times) with diethyl ether. The latter wasdried on MgSO4 and the solvent removed under vacuum.The coupling product was finally isolated with silica gelchromatography. The reaction yields were determined withgas chromatography on a Shimadzu 2014-GC chromatograph. The capillary column was DB-5 and the carrier gaswas helium. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 83% 2: 17% | With iron(III) trichloride hexahydrate; triphenylphosphine; sodium hydroxide In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 20℃; for 0.75h; Sonication; Green chemistry; | Method C: General procedure: The ultrasonic probe was immersed directlyin the reactor. An ultrasonic generator (Sonics VC 505 300W) emitted sound vibration into the reaction mixture. Sonificationwas achieved at a low frequency of 20 kHz (50% amplitude) at room temperature for 45 min. The aryl halideor arylboronic acids (4.5 mmol), the aniline compound (2.25mmol), the ligand (0.05 mmol) and the catalyst FeCl3.6H2O,Ag, CuO or ZrO2) (0.025 mmol) were placed in a reactor. 3mL of solvent were added. After the reaction, the mixturewas extracted (three times) with diethyl ether. The latter wasdried on MgSO4 and the solvent removed under vacuum.The coupling product was finally isolated with silica gelchromatography. The reaction yields were determined withgas chromatography on a Shimadzu 2014-GC chromatograph. The capillary column was DB-5 and the carrier gaswas helium. |
Tags: 1205-64-7 synthesis path| 1205-64-7 SDS| 1205-64-7 COA| 1205-64-7 purity| 1205-64-7 application| 1205-64-7 NMR| 1205-64-7 COA| 1205-64-7 structure
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P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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