Structure of 615-37-2
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CAS No. : | 615-37-2 |
Formula : | C7H7I |
M.W : | 218.04 |
SMILES Code : | CC1=CC=CC=C1I |
MDL No. : | MFCD00001042 |
InChI Key : | RINOYHWVBUKAQE-UHFFFAOYSA-N |
Pubchem ID : | 5128 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.16 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.94 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.32 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.6 |
Solubility | 0.0549 mg/ml ; 0.000252 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.6 |
Solubility | 0.545 mg/ml ; 0.0025 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.74 |
Solubility | 0.0396 mg/ml ; 0.000182 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.54 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.53 |
* 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 |
---|---|---|
99% | Stage #1: With potassium carbonate In toluene at 148℃; for 21 h; Heating / reflux Stage #2: With hydrogenchloride In water Stage #3: With sodium hydroxide In water |
(R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride:; A 3 -necked 100 ml glass reactor was flushed for 15 min with N2 and subsequently charged with 15 g (90.8 mmol) of the above mentioned (3R)-methyl-3-hydroxy-3- phenylpropylamine (>99 percent ee, chiral HPLC), potassium phosphate (28.9 g, 136.2 mmol) and 1.73 g copper(I)iodide (9.8 mmol, 10 mol-percent). 60 ml of toluene was added to the mixture and the suspension was stirred for 5 min. 12.8 ml (100 mmol) of 2-iodotoluene was added and the reaction mixture was heated to reflux for 24 h. After cooling to room temperature, the suspension was filtered and the filter cake was washed with 60 ml of toluene. 75 ml of water was added to the filtrate and the mixture was stirred for 10 min at room temperature. The aqueous phase was brought to pH 1-2 with 30 percent HCl and the phases were separated. 60 ml of toluene was added to the aqueous phase and aqueous NaOH was added until pH 12-14 of the aqueous phase was reached. After stirring for EPO <DP n="16"/>10 min the phases were separated. The organic phase was evaporated under reduced pressure yielding 25 g of an oil.The oil was redissolved in 80 ml of toluene, warmed to 80 °C and 36 g of a 10 percent HCl- ethyl acetate solution was added dropwise to the solution. During cooling of the solution a white solid precipitated. After 5 h at room temperature, the suspension was filtered and the residue was dried in vacuum at about 50 °C to yield 22 g (75.4 mmol, 83 percent) of (R)- N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride.The (R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride salt was placed in a 100 ml reaction vessel and 55 ml of isopropanol was added. Upon heating to reflux temperature all solids were dissolved. Slow cooling to room temperature gave 18.1 g (82 percent) of colorless (R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride (>99 percent ee, HPLC). |
94% | Stage #1: With potassium carbonate In toluene at 148℃; for 21 h; Heating / reflux Stage #2: With hydrogenchloride In water Stage #3: With sodium hydroxide In water |
(R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride:; A 3 -necked 100 ml glass reactor was flushed for 15 min with N2 and subsequently charged with 15 g (90.8 mmol) of the above mentioned (3R)-methyl-3-hydroxy-3- phenylpropylamine (>99 percent ee, chiral HPLC), potassium phosphate (28.9 g, 136.2 mmol) and 1.73 g copper(I)iodide (9.8 mmol, 10 mol-percent). 60 ml of toluene was added to the mixture and the suspension was stirred for 5 min. 12.8 ml (100 mmol) of 2-iodotoluene was added and the reaction mixture was heated to reflux for 24 h. After cooling to room temperature, the suspension was filtered and the filter cake was washed with 60 ml of toluene. 75 ml of water was added to the filtrate and the mixture was stirred for 10 min at room temperature. The aqueous phase was brought to pH 1-2 with 30 percent HCl and the phases were separated. 60 ml of toluene was added to the aqueous phase and aqueous NaOH was added until pH 12-14 of the aqueous phase was reached. After stirring for EPO <DP n="16"/>10 min the phases were separated. The organic phase was evaporated under reduced pressure yielding 25 g of an oil.The oil was redissolved in 80 ml of toluene, warmed to 80 °C and 36 g of a 10 percent HCl- ethyl acetate solution was added dropwise to the solution. During cooling of the solution a white solid precipitated. After 5 h at room temperature, the suspension was filtered and the residue was dried in vacuum at about 50 °C to yield 22 g (75.4 mmol, 83 percent) of (R)- N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride.The (R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride salt was placed in a 100 ml reaction vessel and 55 ml of isopropanol was added. Upon heating to reflux temperature all solids were dissolved. Slow cooling to room temperature gave 18.1 g (82 percent) of colorless (R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride (>99 percent ee, HPLC). |
82% | Stage #1: With potassium phosphate In toluene for 24 h; Heating / reflux Stage #2: With hydrogenchloride In water Stage #3: With sodium hydroxide In water |
(R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride:; A 3 -necked 100 ml glass reactor was flushed for 15 min with N2 and subsequently charged with 15 g (90.8 mmol) of the above mentioned (3R)-methyl-3-hydroxy-3- phenylpropylamine (>99 percent ee, chiral HPLC), potassium phosphate (28.9 g, 136.2 mmol) and 1.73 g copper(I)iodide (9.8 mmol, 10 mol-percent). 60 ml of toluene was added to the mixture and the suspension was stirred for 5 min. 12.8 ml (100 mmol) of 2-iodotoluene was added and the reaction mixture was heated to reflux for 24 h. After cooling to room temperature, the suspension was filtered and the filter cake was washed with 60 ml of toluene. 75 ml of water was added to the filtrate and the mixture was stirred for 10 min at room temperature. The aqueous phase was brought to pH 1-2 with 30 percent HCl and the phases were separated. 60 ml of toluene was added to the aqueous phase and aqueous NaOH was added until pH 12-14 of the aqueous phase was reached. After stirring for EPO <DP n="16"/>10 min the phases were separated. The organic phase was evaporated under reduced pressure yielding 25 g of an oil.The oil was redissolved in 80 ml of toluene, warmed to 80 °C and 36 g of a 10 percent HCl- ethyl acetate solution was added dropwise to the solution. During cooling of the solution a white solid precipitated. After 5 h at room temperature, the suspension was filtered and the residue was dried in vacuum at about 50 °C to yield 22 g (75.4 mmol, 83 percent) of (R)- N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride.The (R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride salt was placed in a 100 ml reaction vessel and 55 ml of isopropanol was added. Upon heating to reflux temperature all solids were dissolved. Slow cooling to room temperature gave 18.1 g (82 percent) of colorless (R)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride (>99 percent ee, HPLC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium 5-methyl-1,3,4-oxadiazole-2-thiolate; basolite C300; In water; N,N-dimethyl-formamide; at 130℃; for 4.25h;Green chemistry; | General procedure: A mixture of iodobenzene (2.0 mmol), potassium 5-methyl-1,3,4-oxadiazole-2-thiolate (1) (3.0 mmol), MOF-199 (8 mg, 10 % mol) were added to a flask containing 2 mL DMF/H2O (20:1), The reaction continued at 130 C under atmospheric conditions until completion. Thereaction progress was controlled by thin-layer chromatography. The reaction mixture was then filtered. The filtrate was evaporated under vacuum, CH2Cl2 (20 ml) was addedand the mixture was washed with H2O (2 x 15 ml). Theorganic layer was dried over anhydrous Na2SO4. The solvent was evaporated to give the crude diaryl disulfide, which was purified by plate chromatography (silica gel,n-hexane-ethyl acetate, 20:1). All spectra of the diaryl disulfides are mentioned in the electronic supplementary material. |
97% | With morpholinium morpholine-1-carbodithioate; copper(l) chloride; potassium hydroxide; In water; N,N-dimethyl-formamide; at 110℃; for 20h;Green chemistry; | General procedure: To a stirred mixture of aryl (alkyl) halide (2.0 mmol), morpholin-4-ium morpholine-4-carbodithioate(0.75 g, 3.0 mmol) in DMF/H2O (2:1) was added CuCl (0.3 g, 3.0 mmol) followed byKOH (2.0 g) and heated at 110C under atmospheric conditions until completion (20 h). Theprogress of the reaction was monitored by TLC. Upon completion of the reaction, the mixturewas cooled to room temperature and then filtered. The filtrate was evaporated under vacuum,CH2Cl2 (20 ml) was added and the mixture was washed with H2O (2 × 15 ml). The combinedorganic layer was dried over Na2SO4, and filtered to afford the crude diaryl (dialkyl) disulfide,which was purified by plate chromatography (silica gel, n-hexane: ethyl acetate, 20:1; in the caseof 3i and 3k was 4:1). |
95% | With indium(III) oxide; ammonia; water; sulfur; In ethanol; at 60℃;Green chemistry; | General procedure: A mixture of alkyl/aryl halide, 1 (1.2 mmol), ammonium hydroxide (1 mmol) and nanosulfur powder (3 mmol, 96 mg) was stirred in 5mL of solvent (ethanol/water (2:1)) at 60 C. Under this stirring condition indium oxide nanoparticles (3 mol-%) were added to it and the reaction was stirred for a period of 10 min to 1 h at 60 C. After completion of the reaction as indicated by thin layer chromatography (TLC), the reaction mixture was cooled to room temperature and a 2:1 mixture of ethyl acetate/water (15 mL) was added and indium oxide was removed by centrifuge. The combined organic extracts were dried with anhydrous sodium sulfate and concentrated to give desired product in high purity. |
92% | With [2,2]bipyridinyl; copper(l) iodide; sodium carbonate; sulfur; aluminium; In N,N-dimethyl-formamide; at 110℃; for 24h;Inert atmosphere; | To a mixture of sulfur (10.6 mg, 0.3 mmol), CuI (8.5 mg, 0.045 mmol), aluminum powder (53-150 μm) (16.2 mg, 0.6 mmol), Na2CO3 (15.9 mg, 0.15 mmol), bpy (7.0 mg, 0.045 mmol), and 2-iodotoluene 1a (65.4 mg, 0.3 mmol), DMF (0.5 mL) was added, and the mixture was stirred at 110 C for 24 h. After the reaction mixture was diluted with Et2O, the solution was washed with H2O and saturated sodium chloride and dried over anhydrous magnesium sulfate. Chromatography on silica gel (hexane) gave di(2-methylphenyl) disulfide (34.0 mg, 92%). 1H NMR (270 MHz, CDCl3) δ 7.49-7.52 (m, 2H), 7.10-7.15 (m, 6H), 2.42 (s, 6H); 13C NMR (67 MHz, CDCl3) δ 137.4, 135.4, 130.3, 128.7, 127.3, 126.7, 20.0. Anal. Calcd for C14H14S2: C, 68.24; H, 5.73. Found: C, 68.19; H, 5.70. |
90% | With carbon disulfide; potassium cyanide; copper(l) iodide; In N,N-dimethyl-formamide; at 20 - 120℃; for 1.7h; | General procedure: KCN (1.1 mmol, 0.07 g) and CS2 (1.3 mmol, 0.07 mL) were added to a flask containing DMF (1 mL) at room temperature. After 15 min, iodobenzene (1.0 mmol, 0.11 mL) and CuI (20 mol%, 0.038 g) were added and the reaction mixture stirred at 120 C. Upon reaction completion (TLC, 1.25 h), the mixture was cooled to room temperature, diluted with H2O (1 mL) and extracted with n-hexane/ethyl acetate (1:1, 4 × 1 mL). The combined organic extracts were concentrated and the residue purified by silica gel column chromatography using n-hexane as eluent to give the pure diphenyldisulfane as a white crystalline powder in 92% (0.10 g) yield. |
89% | With potassium ethyl xanthogenate; potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 8h; | General procedure: A mixture of the requisite alkyl (aryl) halide (2.0 mmol), potassiumO-ethylcarbonodithioate (0.48 g, 3.0 mmol) and MOF-199(8 mg) in DMF (15.0 mL) in a 25 mL round-bottom flask wasstirred at 120 C for 8 h. The reaction was monitored by TLCanalysis. Upon completion of the reaction, the mixture wascooled to room temperature and then filtered. The filtrate wasevaporated under vacuum, CH2Cl2 (20 mL) was added, and themixture was washed with H2O (2 × 15 mL). The combinedorganic layers were dried over Na2SO4, filtered, and solvent wasremoved in vacuo. The residue was purified by thick-layer chromatographyon silica gel (eluting with n-hexane-ethyl acetate,20:1; in the case of 4e and 4f, 4:1 and 2:1, respectively) to givethe corresponding products. |
75% | With 1H-imidazole; copper(l) iodide; sodium thiosulfate pentahydrate; potassium carbonate; In water; dimethyl sulfoxide; at 130℃; for 24h;Green chemistry; | General procedure: A mixture of iodobenzene (1.0 mmol, 0.115 mL),Na2S2O3•5H2O (3 mmol, 248.21 mg), using CuI (0.7 mmol,190.45 mg) catalyst in the presence of K2CO3(2mmol,138.21 mg) and in the presence imidazole (1.6 mmol, 68.08mg) in DMSO/H2O (2 mL) at 130C for 21 h under normal atmospheric conditions until completion. The reaction progresswas controlled by thin-layer chromatography. Also itcan be controlled by color change of litmus paper [38]. Thereaction mixture was then filtered. The filtrate was evaporatedunder vacuum, CH2Cl2 (20 mL) was added and themixture was washed with H2O (2 × 15 mL). The organiclayer was dried over anhydrous Na2SO4. The solvent wasevaporated to give the crude diaryl/alkyl disulfide, whichwas purified by plate chromatography (silica gel, n-hexane-ethyl acetate, 20:1) |
70% | With potassium 5-methyl-1,3,4-oxadiazole-2-thiolate; nickel(II) chloride hexahydrate; ethylene glycol; potassium hydroxide; In water; N,N-dimethyl-formamide; at 130℃; for 8h; | General procedure: A mixture of iodobenzene (2.0 mmol), potassium 5-methyl-1,3,4-oxadiazole-2-thiolate (1, 0.462 g, 3.0 mmol), NiCl2·6H2O (10 mol%) and KOH (1.0 g, 18 mmol) were added to a flask containing DMF-H2O (2 mL, 20:1) and EG (0.11 mL, 2 mmol). The reaction mixture was heated at 130 C under atmospheric conditions until completion, monitored by TLC. The reaction mixture was then filtered, the filtrate was evaporated under reduced pressure, CH2Cl2 (20 mL) was added, and the mixture was washed with H2O (2 × 15 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and the solvent was evaporated to give the crude diaryl/alkyl disulfide, which was purified by preparative TLC (silica gel; n-hexane-EtOAc, 20:1). |
70% | With 1,10-Phenanthroline; potassium sulfide; iron oxide; potassium hydroxide; In N,N-dimethyl-formamide; at 120℃; for 15.5h;Inert atmosphere; Green chemistry; | General procedure: A mixture of aryl iodide (1.0 mmol), K2S(1.0 mmol), Fe3O4 nanoparticle (6 mg), 1,10-Phenanthroline (6 mg) and KOH(0.05 g) were added to a flask containing 2 mL DMF. Thereaction continued at 120 C under N2atmospheric conditionsuntil completion.The reaction progress was controlledby thin-layer chromatography. The reaction mixture wasthen filtered. The filtrate was evaporated under vacuum;afterward, CH2Cl2(20 mL) was added and the mixture waswashed with H2O(2 × 15 mL). The organic layer was driedover anhydrous Na2SO4.The solvent was evaporated to givethe crude diaryl disulfide, which was purified by plate chromatography(silica gel, n-hexane-ethyl acetate, 20:1). (Fordetails, please see Electronic Supplementary Information.) |
68% | With potassium sulfide; nickel(II) chloride hexahydrate; acetylacetone; potassium hydroxide; In water; N,N-dimethyl-formamide; at 110℃; for 24h; | General procedure: To a stirred mixture of aryl (primary alkyl) halide (2.0 mmol), 0.33 g potassium sulfide (3.0 mmol) and acac (20 mol%) in 2 cm3 DMF (containing a few drops water),NiCl2.6H2O (10 mol%) and then 1.0 g KOH (18.0 mmol) were added and the whole reaction mixture was heated at 110 C under atmospheric conditions until completion. The progress of the reaction was monitored by TLC. Upon completion of the reaction, the mixture was cooled to room temperature. Then, the pH of mixture was adjusted to 7 with 5 % HCl and filtered. The filtrate was evaporated under vacuum, 20 cm3 ethyl acetate was added and the mixture was washed with H2O (2 x 15 cm3). The combined organic layer was dried over Na2SO4 and filtered to afford the crude diaryldisulfide and dialkyldisulfide, which was purified by preparative chromatography (silica gel, n-hexane:ethyl acetate 20:1; in the case of Table 3, entries 12-15 was 4:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With potassium carbonate; at 85℃; for 24h;Inert atmosphere; Green chemistry; | General procedure: To a mixture of the catalyst 3 (20mg containing 0.05mol% Pd for aryl iodides and 40mg containing 0.1mol% Pd for aryl bromides and chlorides), aryl halide (1mmol), alkyne (1.5mmol), and K2CO3 (1.5mmol, 207mg) was added PEG 200 (2mL) under argon atmosphere. The reaction mixture was stirred for the appropriate reaction time at 85 or 130C (see, Table 2). The progress of the reaction was monitored by using gas chromatography. After completion of the reaction, pure products were obtained by using column chromatography with hexane and ethyl acetate as eluents. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With sodium t-butanolate; In dimethyl sulfoxide; at 110℃; for 12h;Green chemistry; | General procedure: Aryl halide (1.0 mmol), secondary amines (1mmol),2 mmol tBuONa and 0.2 mol% ofPd/Nf-G catalyst were addedin a 1 mL DMSO and the reaction was carried at 110C for 12h. The progress ofthe reaction was monitored by Gas Chromatography (GC). After completion ofreaction, the reaction mixture was cooled to room temperature and it was extracted with ethyl acetate. The catalyst was easily recovered by simple filtration followed by washing with ethanol and drying and preserved for nextruns. The pure products were obtained by column chromatography using hexane:ethyl acetate as the eluent. The preserved catalyst reused in a subsequent runfor recyclability study. The conversion of reactant was determined by Gaschromatography (GC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium azide; copper diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 95℃; for 5h; | 1.0 mmol o-methyl iodobenzene,1.2 mmol sodium azide,0.15 mmol DBUAnd 0.1mmol of copper acetate were sequentially added to a reaction flask equipped with 3mL of dimethyl sulfoxide,The reaction mixture was stirred at 95 C for 5.0 h,TLC was followed until the reaction was complete,A few drops of aqueous ammonia were added to the reaction mixture,Then extracted with ethyl acetate (10 mL × 3),Then washed once with saturated saline,dry,Suction filtration,Remove the solvent,Purification by column chromatography gave the desired product,Yield 75%. |
75% | With sodium azide; copper(II) acetate monohydrate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 95℃; for 5h; | General procedure: CAUTION: Azides are potentially explosive and so appropriateprecautions against blast must be taken when preparing, handlingand heating them. Reactions must be carried out on a small scale. A mixture of the aryl iodide (1.0 mmol), sodium azide (1.2 mmol),DBU (0.15 mmol) and Cu(OAc)2·H2O (0.1 mmol) in DMSO (3.0 mL)in a 10 mL flask was heated to 95 C (the temperature in the reaction flask was monitored) for 1.5-5.0 h. After the reaction was completed asjudged by TLC, the cooled mixture was poured into water (30 mL)containing several drops of ammonia. The resulting aqueous phase was extracted with ethyl acetate (3 × 30 mL). The combined organic phases were washed with brine (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was loaded on asilica gel column and eluted with petroleum ether (boiling range 60-90 C)/ethyl acetate to afford the product. |
82%Chromat. | With sodium azide; bis(2,2,6,6-tetramethyl-3,5-heptanedionato)copper(II); In N,N-dimethyl-formamide; at 100℃; for 12h;Sealed tube; | General procedure: In a 10-mL sealed tube with a spin bar, halobenzene (1 mmol) was used, or in 25-ml round-bottom flask with a spin bar equipped with condenser, boronic acid (1 mmol), was used and DMF (4 ml), sodium azide (1.2 mmol), and Cu(TMHD)2 (0.20 mmol) were added and containers were sealed properly. The reaction mixturewas heated at the 100 C with stirring for desired time and cooled to room temperatureon completion of the reaction. Then the mixture poured into 15 ml of ice-coldwater and extracted with diethyl ether (310 ml). The residue obtained was purifiedby column chromatography (silica gel, 60:20 mesh; petroleum ether = ethyl acetate98:2%) to afford the desired azide products. The organic solution was analyzed by GC and confirmed by GCMS and NMR. The purity of compounds was determinedby GC-MS analysis. All products are known in the literature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium phosphate; In N,N-dimethyl-formamide; for 4h;Reflux; | General procedure: Aryl boronic acid (1.0 mmol), aryl iodide (1.0 mmol), NitmtaaDFNS (6 mg), DMF (10 mL) and K3PO4 (5 mmol) were released to a100 mL autoclave. The autoclave was closed, purified twice with carbonmonoxide gas, pressurized with 2 MPa of carbon monoxide, and thenheated under reflux for 4 h. Then, the reaction blend was cooled to roomtemperature and the remaining CO gas was carefully evacuated and the reactor was opened. The reaction was monitored by TLC. Uponcompletion, ethanol was released to the reaction blend and the catalystwas isolated by filtration. Then the solvent was eliminated from thesolution under decreased pressure and the final product was purified byrecrystallization employing ethyl acetate/n-hexane. |
89% | With triethylamine; In water; at 130℃; under 22502.3 Torr; for 6h;Autoclave; | In a typical experiment, known quantities of iodobenzene (1.0 mmol), phenylacetylene (1.2 mmol), P(DVB-IL)-Pd (20 mg, Pd 0.5 mol %), Et3N (0.4 mL, 2.4 mmol), and distilled water (5.0 mL) were charged into the reactor. The autoclave was closed, purged three times with CO, pressurized to 3.0 MPa with CO, and then stirred at 130 C for 6 h. After cooling down to room temperature, the reaction mixture was analyzed by GC-MS and then worked up by removing water under vacuum and the residue was purified by chromatography on silica gel (eluting solvent hexane:ethyl acetate). |
75% | With triethylamine; In 1,2-dimethoxyethane; at 80℃; under 3040.2 Torr; for 7h;Autoclave;Catalytic behavior; | General procedure: To a 100 mL autoclave, aryl iodide (1 mmol), alkyne (1.15 mmol),Pd(II)APTESK10 (0.03 g), Et3N (2 mmol) and solvent (10 mL) wereadded. The autoclave was closed, flushed two times with carbon monoxide, pressurized with 4 atm of CO, and heated at 80 C for 7 h. After the completion of the reaction, the reactor was cooled to room temperature, and the remaining CO gas was carefully vented, and the reactor was opened. The reactor vessel was thoroughly washed with ethyl acetate (3 × 10 mL) to remove any trace of product and catalyst if present. The catalyst was filtered, and the filtrate washed with brine (2 × 10 mL), dried over anhydous Na2SO4, and the solvent evaporated under vacuum. Purification of residue was carried out by column chromatography (silica gel, 120-200 mesh,petroleum ether/ethyl acetate) to afford the desired product. |
60% | With triethylamine; In N,N-dimethyl-formamide; at 80℃; under 760.051 Torr; for 6h;Schlenk technique; | General procedure: To a 50 mL Schlenk flask were added aryl iodide (1 mmol), alkyne(1.2 mmol), Et3N (3 mmol), Pd/DNA (containing 0.01 mmol of Pd) and3 mL of DMF. The flask was cooled in liquid nitrogen, evacuated andconnected with CO balloon. The reaction mixture was stirred for 6 h at80 C. After that time, the flask was cooled down to ambient temperatureand 5 mL of H2O was added. The products were separated by extraction,using 3×7 mL of Et2O, and analyzed by GC-FID with an internalstandard (mesitylene, 0.076 mL). |
100%Chromat. | With bis-[1-(5’-diphenylphosphinothiazol-2’-yl)-imidazolyl]dichloropalladium(II); triethylamine; In N,N-dimethyl-formamide; at 90℃; under 7500.75 Torr; for 1.5h;Autoclave; | General procedure: In a typical experiment, the isolated crystalline precatalyst 1A (or 2A, 0.005 mmol) was sequentially mixed with 3 mL of solvent (DMF or [Bmim]PF6 if required), iodobenzene (5mmol), phenylacetylene (6 mmol), and Et3N (7.5 mmol). The obtained mixture was placed in a sealed Teflon-lined stainless steel autoclave, purged with syngas (CO, 1.0 MPa) and then stirred vigorously at the required temperature for the appointed time. Upon completion of the reaction, the mixture wasc ooled to room temperature and the pressure was carefully released. The reaction mixture was extracted with diethyl ether(5 mL 3). The ether fractions were combined and then analyzedby GC to determine the conversion of PhI (1-dodecane as an internal standard) and the selectivity for the carbonylative products (normalization method). The structures of the carbonylative products were further confirmed by GC-MS. |
95%Chromat. | With C37H29Br2N3OPd; triethylamine; In toluene; at 100℃; under 15001.5 Torr; for 18h;Autoclave; Sealed tube; | Add in a 50 mL autoclave and add 5 mL of toluene.1 mmol 2-methyliodobenzene, 1.2 mmol phenylacetylene, 2.0 mmol triethylamine,0.5 mol% benzimidazole nitrogen heterocyclic carbene palladium metal complex (relative to iodobenzene).The reactor was sealed, and the reactor was replaced three times with carbon monoxide to seal the reactor.The CO gas pressure is 2.0 MPa,The temperature is slowly increased to 100 C by the temperature controller.The reaction was carried out for 18 hours, cooled to room temperature, and the kettle was discharged.The liquid obtained by the reaction was qualitatively analyzed by Agilent 6890/5973 GC/MS, and the target product was obtained.1-(2-tolyl)-3-phenyl-2-propyn-1-oneThe selectivity is greater than 99% and the isolated yield is 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate; In ethanol; water; at 90℃; for 24h;Green chemistry; | General procedure: A mixture of arylhalide (1 mmol), styrene (1 mmol), K2CO3(1 mmol), and nano Pd/ZnO (0.009 g, which contains 832 × 10-8mol% of Pd which was determined by ICP) in H2O (1 mL) was placed in a 25 mL round bottom flask. In the case of the substrates whichare insoluble in water, a mixture of H2O/EtOH (1:1) was used as solvent. The mixture was stirred at 90C. After the reaction was finished, the reaction mixture was cooled to the room tempera-ture, diluted with ethyl acetate (5 mL), and the slurry was stirred at room temperature to ensure removal of the product from the surface of the catalyst. Then it was centrifuged to separate the cata-lyst. The centrifugate was washed with water (2 × 5 mL), dried over anhydrous sodium sulfate, further concentrated under reduced pressure, and purified by column chromatography on silicagel to give the desired product. |
89% | With cetyltrimethylammonim bromide; potassium carbonate; In water; at 80℃; for 8h;Green chemistry; | General procedure: Preparation of (E)-1,2-diphenylethene; typical procedure To a mixture of Au/Pd NPs (0.3 mol %) in H2O (2.0 mL), an iodoarene (1.0 mmol), styrene (1.5 mmol), K2CO3 (2.0 mmol), CTAB (0.5 mmol) and H2O (3.0 mL) were added and the mixture was vigorously stirred at 80 C for 8 h. After completion (as monitored by GC and TLC), the product was extracted with EtOAc. The organic phase was separated, dried over anhydrous MgSO4, and evaporated under reduced pressure. The residue was purified by column chromatography. The yields of the products are based on the aryl halide. All the products are known and the melting points were consistent with those reported in the literature.<ce-sup primary_key="ce-sup-328699-none">1,7,8 |
85% | With potassium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 3h; | General procedure: A suspension of aryl halide (1.0 mmol), K2CO3 (2.0 mmol), Fe3O4SiO2-EDTA-Pd (0.008 g, 0.4 mol%) in H2O/DMF [2/1 (v/v)] (3 mL) was mixed in a reaction flask and n-butylacrylate or styrene (1.2 mmol) was added. The reaction mixture was stirred at 100 C for an appropriate time. After completion of the reaction (monitored by TLC), it was cold at room temperature, diluted with ethyl acetate (10 mL) and then the catalyst was separated from the solution by an external magnetic field. The organic phase was separated and dried over MgSO4 and the solvent was then removed under reduced pressure. Pure products were obtained after isolation of the residue by column chromatography on silica (hexane/ethyl acetate). |
81% | With sodium acetate; In N,N-dimethyl-formamide; at 110℃; for 24h; | General procedure: Degassed solvent (DMF), aryl halide(1.0 mmol), olefin (1.0 mmol), base (1.5 mmol), and the nanocrystal catalyst(1.0 mol %) were added to a round-bottom flask, which was backfilled withargon. The reaction mixture was stirred for 24 h at 110 C. After the reaction,the mixture was cooled to room temperature and the catalyst was separatedusing a magnet. The mixture containing products was partitioned betweenmethylene chloride and water and organic layer was concentrated and purifiedthrough flash chromatography using hexane and ethyl acetate (20:1 v/v) as aneluent. The separated nanocrystal catalyst was washed several times withhexane, methylene chloride, ethanol and then dried for the recyclingexperiment. |
73% | With N-(diphenylphosphino)tributylammonium chloride; sodium hydroxide; palladium dichloride; at 120℃; for 2h; | General procedure: Aryl halides (1.0 mmol) were added to a flask containing IL2 (0.5 mmol, 0.20 g), PdCl2 (3 mol%, 0.0053 g), NaOH (2.0 mmol, 0.08 g) and olefin (2.0 mmol) and the mixture was stirred at 120 C. After completion of the reaction, which was detected by TLC analyses, the mixture was cooled to room temperature and the coupled products were extracted with diethyl ether (3 × 3 mL). The solvent was then evaporated to leave the crude products, which were purified by column chromatography over silica gel using n-hexane/ethyl acetate (4:1) as the eluent to give pure products. The products were identified by their spectral data and comparison with authentic samples. |
95%Chromat. | With caesium carbonate; In toluene; at 80℃; for 5h;Inert atmosphere; | In a typical reaction, styrene (1.0 mmol) and aryl halide (1.5 mmol) were reacted in a homogeneous mixture of toluene and PEG-600 (20 ml, 3:1) in the presence of 3 mol % of Cl2PdPEGD catalyst(34.4 mg) and Cs2CO3 (1.5 mmol), under a nitrogen atmosphere at 80 C for 5 h until complete consumption of aryl halide. The reaction progress was monitored by TLC and GC analysis. The mixture was cooled to room temperature and 20 ml of n-hexane was added to separate lower catalyst-philic PEG phase from upper product phase. The product was isolated by decantation and evaporation of solvents under vacuum. Catalyst-philic PEG phase containing polyether palladium catalyst was subjected to reuse by charging with the same amount of the substrates styrene (1.0 mmol) and aryl halide (1.5 mmol), Cs2CO3 (2.0 mmol) and toluene. The identity and purity of the products were confirmed by GC and GC-MS. |
With sodium tetrachloropalladate(II); sodium hydrogencarbonate; In n-heptane; water; at 100℃; for 5h;Catalytic behavior; | General procedure: To a stirred solution of aryl halide (1 mmol) in 2.5 mL heptane were added the alkene (1.5 mmol) and the internal standard (unde-cane, 0.3 mmol). An aqueous solution (2.5 mL) containing ligand 1or 2 (0.1 mmol), Na2PdCl4(0.005 mmol) and NaHCO3(1.5 mmol)was then added. The reaction mixture was heated at 100C for 18 h.The reaction mixture was cooled to room temperature. Once the organic phase has been recovered, the aqueous phase was washed twice with diethyl ether (2 × 2 mL). The combined organic phases were dried over anhydrous MgSO4 and heptane was removed under vacuum. The residue was purified by chromatography over a silica gel column. Elution with 10% ethyl acetate - heptane gave the expected bisaryl products as colorless oils. | |
With triethylamine; In N,N-dimethyl-formamide; at 100℃; for 12h;Sealed tube; | General procedure: A mixture of aryl iodide (1.0 mmol), methyl acrylate (1.1 mmol), triethylamine (2.0 mmol), and an adequate amount of copper catalyst (0.33 mol%) was taken in a round-bottom flask and stirred in DMF (5.0 mL) at 100 C, and the progress of the reaction was monitored by GC.48 At the end of the reaction, the mixture was cooled to room temperature and the catalyst was isolated by magnetic decantation. The recovered catalyst was thoroughly rinsed with ethyl acetate and distilled water, dried at room temperature, and used without any pretreatment for the next runs. The recyclability of the catalyst was screened in the reaction between iodobenzene and methyl acrylate according to the above procedure. | |
With tetrabutylammomium bromide; [Pd(3-(2-fluorobenzyl)-1-(4-methoxyphenyl)-1H-imidazolline-2-ylidene)Br2(pyridine)]; potassium carbonate; In water; at 100℃; for 12h; | General procedure: A round-bottomed flask (50 mL) equipped with a condenserand a magnetic stirring bar was charged with aryl halide(1 mmol), styrene (1.5 mmol), K2CO3 (3 mmol) and 1(1 mol%) in water (3 mL) were allowed to stir at 100 C inair. The progress of the reaction was monitored by TLC(hexane/ethyl acetate, 4:1). After completion of the reaction, the reaction mixture was cooled to room temperature.Ethyl acetate (15 mL) was added to the reaction mixture.The organic layer was washed with water (3 x 10 mL) anddried over anhydrous MgSO4 and the reaction mixture wasanalysed with GC-MS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With ammonium hydroxide; caesium carbonate; In acetonitrile; for 8h;Reflux; Green chemistry; | General procedure: A mixture of the aryl halide (1 mmol), NH4OH (2 mmol), Cs2CO3 (1 mmol) and P4PVy-CuI (0.1 g) in CH3CN (10 mL) was stirred at reflux temperature. After reaction completion (moitored by TLC), the catalyst was recovered by filtration and solvent was evaporated. The residue was poured into a saturated NaCl solution, extracted with ethyl acetate and dried over anhydrous MgSO4. Evaporation of the solvent was followed by column chromatography on silica gel afforded the pure products. |
70% | With acetamidine hydrochloride; caesium carbonate; In N,N-dimethyl-formamide; at 140℃; for 20h;Inert atmosphere; Green chemistry; | General procedure: A two-necked flask equipped with a magnetic stirring bar was charged with Cs2CO3 (2 or 3 mmol), MCM-41-L-proline-CuI (0.1 mmol), aryl iodide (1.0 mmol), acetamidine hydrochloride (1.2 or 2 mmol) and DMF (3.0 mL) under Ar. The reaction mixture was stirred at 130 or 140 C for 20 h. After being cooled to room temperature, the mixture was diluted with CH2Cl2 (10 mL) and filtered. The catalyst was washed with distilled water (2 × 5 mL) and EtOH (2 × 5 mL) and air dried when reused in the next run. The filtrate was concentrated with the aid of a rotary evaporator and the residue was purified by column chromatography on silica gel using petroleum ether (30-60 C)/ethylacetate (10:1 to 1:1) as eluent to give the desired product 2. All the products 2a-z are known compounds. |
55% | With ammonium hydroxide; copper(l) iodide; N,N'-bis(3,5-dimethoxyphenyl)cyclopentane-1,1-dicarboxamide; caesium carbonate; In dimethyl sulfoxide; at 90℃; for 24h;Inert atmosphere; Sealed tube; | General procedure: A 10 mL flask was charged with a magnetic stir bar, CuI (19 mg,10 mol%), L2 (86 mg, 20 mol%), Cs2CO3 (651 mg, 2 mmol) and solid aryl iodides (1.0 mmol). The tube was evacuated and backfilled with argon (this procedure was repeated three times). Under a counter flow of Argon, DMSO (1.0 mL), 1.0 mmol aryl iodides (if liquid), 0.9 mL (12.0 mmol) aqueous ammonia (28%) were added by syringe slowly. The reaction mixture was allowed to stir under argon at room temperature for 24 h. Then the mixture was diluted with 30 ml dichloromethane and passed through a fritted glass filter, the filter cake being further washed with 15 ml dichloromethane, dried over Na2SO4, filtered and the most solvent was removed under vacuum. The residue was purified by column chromatography on silica gel with an eluent of petroleum ether and ethyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With copper(I) oxide; caesium carbonate; In N,N-dimethyl-formamide; at 135℃; for 30h;Inert atmosphere; | General procedure: A sealable vial equipped with a magnetic stir bar was charged with Cs2CO3 (652 mg, 2.0 mmol), Cu2O (14.0 mg, 0.10 mmol) under a nitrogen atmosphere. The aperture of the vial was then covered with a rubber septum. Under a nitrogen atmosphere, alkyl alkyne (4, 1.5 mmol), aryl iodide (2, 1.0 mmol) and DMF (0.5mL) were added by syringe. The septum was then replaced by a screw cap containing a Teflon-coated septum, and the reaction vessel was placed at 135 C. After stirring at this temperature for 48 h, the heterogeneous mixture was cooled to room temperature and diluted with ethyl acetate (20 mL). The resulting solution was filtered through a pad of silica gel then washed with ethyl acetate (20 mL) and concentrated to give the crude material which was then purified by column chromatography on silica gel toyield alkyne 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With copper(l) iodide; 2-(2-benzoylhydrazine-1-carbonyl)-1-benzylpyrrolidine 1-oxide; caesium carbonate; In acetonitrile; at 80℃; for 12h;Inert atmosphere; Sealed tube; | General procedure: CuI (19.2 mg, 0.1 mmol, 10 mol%), Cs2CO3 (650 mg, 2.0 mmol) and L2 (34 mg, 0.1 mmol, 10 mol%) were added to a re-sealable 25 mL test tubes with Teflon septa. The tube was evacuated and backfilled three times with nitrogen. Add the corresponding solvent (EtOH or CH3CN, 1 mL) via syringe under countercurrent nitrogenflow, continue adding halides (1.5 mmol) and nucleophile (1.0 mmol), seal the test tube. The reaction mixture was heated at 80 C for 12 h, and then allowed to cool to room temperature. After the reaction mixture was diluted with CH2Cl2, the precipitate was removed by filtration and washed with water. After extraction, the organic phase was dried over anhydrous sodium sulfate and concentrated by rotary evaporation. The residue was purified by column chromatography. |
80% | With potassium phosphate; copper(l) iodide; 2-((2-isopropylphenylimino)methyl)phenol; In 1,4-dioxane; at 20 - 101℃; for 24h;Schlenk technique; Inert atmosphere; | General procedure: 2-((2-Isopropylphenylimino)methyl)phenol (15mol%), CuI (5mol%), phenol (1.5mmol, 141mg) and K3PO4 (2.0mmol, 425mg) were added to a screw-capped Schlenk tube under argon. The tube was then evacuated and backfilled with argon (three cycles). Iodobenzene (1mmol, 0.11mL) and dry dioxane (0.5mL) were added by syringe at room temperature. The reaction mixture was stirred at needed temperature (101C) for 24h. The reaction mixture was allowed to reach room temperature and then diluted with dichloromethane (10mL). The slurry was filtered, and the filter cake was washed with 10mL of dichloromethane. The solvent was removed in vacuo, and the residue was purified by column chromatography on silica gel to afford the desired product (3aa). |
73% | With tetrabutylammomium bromide; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 24h; | General procedure: Cu- catalyst (0.05 g) in DMSO (5 mL) was taken in a 100 mLround bottom flask and stirred at room temperature for 10 min.Then aryl halide (1 mmol), phenol (1 mmol), tetrabutylammoniumbromide (tBu4NBr) (0.1 mmol), Cs2CO3(1 mmol) and DMSO (5 mL)were added to it. The final reaction mixture was heated at 120Cunder an open air condition. The reaction mixtures were collectedat different time intervals and identified by GC-MS and quantifiedby GC. After the completion of the reaction, the catalyst was fil-tered off and washed with water followed by acetone and dried inoven. The filtrate was extracted with ethyl acetate (3 × 20 mL) andthe combined organic layers were dried with anhydrous Na2SO4byvacuum. The filtrate was concentrated by vacuum and the result-ing residue was purified by column chromatography on silica gelto provide the desired product. |
51% | With copper(I) oxide; caesium carbonate; imidazole-4-carboxylic acid; In acetonitrile; at 80℃; for 24h; | General procedure: To a screw-capped vial (4-mL) were added Cs2CO3 (1.0 mmol, 325 mg), Cu2O (0.005 mmol, 0.7 mg), 1H-imidazole-4-carboxylic acid (0.01 mmol, 1.1 mg) and acetonitrile (0.25 mL). The vial was sealed with septum and allowed to stir for a while; the iodoarene (0.5 mmol) and phenol (0.6 mmol) were then injected into the reaction mixture via a syringe. The septum was removed, and the vial was sealed with a screw cap. The reaction mixture was stirred at 80 oC for 24 h. The crude reaction mixture was diluted with CH2Cl2, filtered through a thin Celite pad, and concentrated in vacuo. The residue was isolated through a column chromatography by using hexane and ethyl acetate as eluent to give the pure product. Products 3a-v were obtained according to this procedure. The known structures were characterized by the 1H NMR and 13C NMR of reported literatures.1-3 Spectral data, 1H NMR and 13C NMR spectra for all the new compounds are listed below. |
50% | With tetrabutylammomium bromide; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 16h; | General procedure: Polymer supported Cu(II) catalyst (0.05 g, 0.0098 mmol) in DMSO (5 mL) was taken in a 100 ml R.B flask and stirred at room temperature for 10 min. Then aryl halide (1 mmol), phenol(1 mmol), tetrabutylammonium bromide (tBu4NBr) (0.1 mmol),Cs2CO3 (1 mmol) and DMSO (5 mL) were added to it. The final reaction mixture was refluxed at 120 C under an open air condition.The reaction mixtures were collected at different time intervals and identified by GCMS and quantified by GC. After the completion of the reaction, the catalyst was filtered off and washed with water followed by acetone and dried in oven. The filtrate was extracted with ethyl acetate (3 x 20 ml) and the combined organic layers were dried with anhydrous Na2SO4 by vacuum. The filtrate was concentrated by vacuum and the resulting residue was purified by column chromatography on silica gel to provide the desired product. |
41% | With copper(l) iodide; potassium carbonate; 1,1,3,3-tetramethyl-1,3-bis(3-pyridinyl)disiloxane; In N,N-dimethyl-formamide; at 100℃; for 24h;Inert atmosphere; | General procedure: Aryl iodide or bromides (1 mmol), ArOH (1 mmol), CuI(20 mol%), and dimethyl di (2-pyridyl)silane (20 mol%) were placed in a small round-bottom flask. DMF (3 mL) and K2CO3(276 mg, 2 mmol) were then added together. The mixture was stirred for 24 h at 100C in nitrogen atmosphere. The reaction mixture was cooled to room temperature. Ethyl acetate(10 mL) and H2O (1 mL) were added and the mixture was stirred. The organic layer was separated and the aqueous layer was extracted twice more with ethyl acetate (10 mL). Combined organic layer was dried overNa2SO4 and filtered. The filtrate was concentrated and the resulting residue was purified by silica gelchromatography and afforded the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | General procedure: A 15mL glass vial equipped with magnetic stir bar was charged with 1mmol of aryl iodide substrate, arene (3mL, 67 equiv), tert-potassium butoxide (2 equiv), 35mg of IrPyBzASMNPs (0.42mol%) catalyst in 1mL DMSO, purged with nitrogen and sealed with rubber cap. Afterwards, the system was sonicated for 15min and irradiated with the 2×12W white LEDs by keeping at a distance of 10cm for 18h under constant stirring. After completion of the reaction, the catalyst was separated via external magnet and the supernatant was extracted with (3×30mL) ethyl acetate and water. Subsequently, the organic layer was collected, rotary evaporated and further purified by silica gel column chromatography using hexane. | |
54% | With cesium hydroxide; 5,10,15,20-tetra(p-tolyl)porphyrin; tert-butyl alcohol; at 200℃; for 4h;Darkness; | H2(ttp) (7.5 mg, 0.0112 mmol), 2-iodotoluene (28 μL, 0.224mmol), CsOH (335 mg, 2.24 mmol), tBuOH (210 μL, 2.24 mmol) were added inbenzene (2.0 mL, 22.4 mmol). The mixture was heated at 200 C for 4 h to afford54% 2-methylbiphenyl2 (2c). |
54% | With potassium 2-methylbutan-2-olate; N,N`-dimethylethylenediamine; at 80℃; for 24h;Inert atmosphere; | General procedure: A Schlenk tube was charged with t-AmOK (1.5 mmol) under anatmosphere of nitrogen, and the solvent (toluene) was removedunder reduced pressure. Then 4-iodoanisole (117 mg, 0.5 mmol),ligand and benzene (4.0 mL) was added. The resulting mixture was stirred at 80 C for 24 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate (10 mL3). The organic layers were combined, dried over Na2SO4 and concentrated under reduced pressure, and then purified by silica gel chromatograph (petroleum ether) to yield the desired product as a white solid. |
51% | With (5,10,15,20-tetrakis(p-methoxyphenyl)-21H,23H-porphyrinate)cobalt(II); potassium hydroxide; tert-butyl alcohol; at 200℃; for 2h;Inert atmosphere; Darkness; | CoII(t4-OMepp) (0.0112 mmol), aryl halide (0.224 mmol),KOH (2.24 mmol), tBuOH (2.24 mmol) were added in benzene (2.0 mL, 22.4 mmol).The mixture was degassed for three freeze-pump-thaw cycles and heated at 200 C. AfterGCMS analysis of reaction mixture to confirm complete consumption of aryl halide, thereaction mixture was distilled under reduced pressure at room temperature to remove the solvent. The crude residue was purified by column chromatography (silica gel, 230-400mesh) eluting with hexane to afford the biaryls (2). |
20% | With potassium tert-butylate; at 100℃; for 16h;Schlenk technique; Sealed tube; Irradiation; | General procedure: Method A: in a glove box, a 25 mL Schlenk tube equipped with a stir bar was charged with aryl iodides (0.25 mmol),KOtBu (56 mg, 0.5 mmol), and benzene (2.0 mL) was added by syringe. Then the Schlenk tube was sealed by a Teflon screw cap and placed in an oil bath at 100 C (preheated to 100 C) with one 24 W CFL (approximately 5 cm away). The reaction mixture was allowed to stir for 16 h. After being cooled down, the solvent was removed in vacuo and the residue was purified by chromatography on silica gel (eluent:diethyl ether/petroleum ether) to provide the corresponding product. Method B: in a glove box, a 25 mL Schlenk tube equipped with a stir bar was charged with aryl iodides (0.25 mmol), bathophenanthroline (8.3 mg, 0.025 mmol), KOtBu(56 mg, 0.5 mmol), and benzene (2.0 mL) was added by syringe. Then the Schlenk tube was sealed by a Teflon screw cap and placed with one 24 W CFL (approximately 3 cm away). The reaction mixture was allowed to stir for36 h. Then the solvent was removed in vacuo and the residue was purified by chromatography on silica gel (eluent:diethyl ether/petroleum ether) to provide the corresponding product. |
43%Chromat. | With fullerene-C60; potassium hydroxide; tert-butyl alcohol; at 200℃; for 13h;Darkness; | General procedure: C60 (0.00224 mmol), aryl halides (0.224 mmol), KOH(4.48 mmol), and tBuOH (2.24 mmol) were dissolved in benzene(2.0 mL, 22.4 mmol). The mixture was heated at 200 C. Afterconfirming the complete consumption of the aryl halide by GCeMSanalysis the solvent was removed by rotary evaporator. The cruderesidue was purified by column chromatography (silica gel,230e400 mesh) eluting with hexane to afford the correspondingbiaryls 1. |
19%Chromat. | With N1,N2-bis(4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluorononyl)ethane-1,2-diamine; potassium tert-butylate; at 120℃; for 24h;Sealed tube; | General procedure: A reaction tube was charged with KOt-Bu (280.0 mg, 2.5 mmol) at room temperature, and then, 4-iodotoluene (109.0 mg, 0.5 mmol), fluorous ethylenediamine L (1170.0 mg, 1.5 mmol) and benzene (6.0 mL) were added. The resulting mixture was stirred at 120 C for 24 h in this sealed tube equipped with a Teflon plug. After cooling to room temperature, (the fluorous ligand can be recovered by extraction with perfluorotoluene 5 mL × 3, 91% recovery yield ) the reaction mixture was quenched and extracted with ethyl acetate (10 mL × 3). The organic layers were combined, dried over Na2SO4 and concentrated under reduced pressure, and then purified by silica gel chromatography (petroleum ether) to yield the desired product as a white solid (52.9 mg, 63% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | With copper(l) iodide; (1S,2S)-N,N'-dimethyl-1,2-diaminocyclohexane; at 140℃; for 3h; | A flask was charged with 2-iodotoluene (0.964mL, 7.57 mmol), <strong>[5932-27-4]ethyl-1H-pyrazole-3-carboxylate</strong> (1.00 g,7.14 mmol), Cul (272 mg, 1.43 mmol), trans-N,N'-dimethylcyclohexane-1,2-diamine (0.451 mL, 2.86 mmol), and K2CO3 (3.15 g, 22.8 mmol). The reaction mixture was then heated to 140° C. for 3 h. The reaction was then partitioned between CH2C12 and saturated aqueous NH4C1 and separated.The organic layer was washed with water, dried over Na2SO4, filtered and concentrated. The crude was purified via flash chromatography on silica gel (90:10-70:30 hexanes:methyl tert-butyl ether) to give the product (238 mg, 1.03mmol, 14percent) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With [ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; potassium carbonate; triphenylphosphine; In benzene; at 150℃; for 24h;Sealed tube; | General procedure: In a 30-mL sealed tube, <strong>[2622-63-1]1-methyl-2-phenylbenzimidazole</strong> (1, 0.25mmol), [RuCl2(p-cymene)]2 (0.0125 mmol), Ph3P (0.075 mmol),K2CO3 (0.50 mmol), and iodoarene (0.25 mmol) were combined inanhydrous benzene (2 mL) under air. The mixture was then stirredat 150 °C for 24 h. The mixture was cooled to r.t., diluted with EtOAc, and filtered through a small pad of Celite. The filtrate was concentrated in vacuo and purified by flash chromatography (silicagel, EtOAc?hexane) to give the analytically pure 2-(biphenyl-2-yl)benzimidazoles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; In toluene; at 130℃; for 18h;Inert atmosphere; | In a 300 mL three-necked flask vacuum dried and purged with nitrogen, 14 g (73 mmol) of <strong>[53848-17-2]2-bromo-6-methylaniline</strong>,17 g (80 mmol) of 2-iodotoluene,12 g (1.2 × 102 mmol) of sodium tert-butoxide,0.67 g (0.73 mmol) of tris (dibenzylideneacetone) dipalladium (0) and 0.81 g (1.5 mmol) of 1,1'-bis (diphenylphosphino) ferrocene were added. To the mixture was added 160 mL of dehydrated toluene, and the mixture was refluxed at 130 C. for 18 hours under a nitrogen atmosphere.After stirring, the temperature was returned to room temperature, ethyl acetate and water were added to the mixture, and the mixture was subjected to liquid separation operation, and the organic layer was washed with saturated brine. After washing, anhydrous magnesium sulfate was added to the mixture, dried and suction filtered to obtain a filtrate. The resulting filtrate was concentrated. The concentrated mixture was purified by silica gel column chromatography with 100% hexane. The obtained fraction was concentrated to obtain a yellow liquid (intermediate D-1; 2-bromo-6-methyl-N- (ortho-tolyl) aniline) in a yield of 15 g in a yield of 77%. |
Tags: 615-37-2 synthesis path| 615-37-2 SDS| 615-37-2 COA| 615-37-2 purity| 615-37-2 application| 615-37-2 NMR| 615-37-2 COA| 615-37-2 structure
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