Structure of 59046-72-9
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CAS No. : | 59046-72-9 |
Formula : | C15H10O |
M.W : | 206.24 |
SMILES Code : | O=CC1=CC=CC=C1C#CC2=CC=CC=C2 |
MDL No. : | MFCD09030317 |
InChI Key : | SDSQNHMKRHPAIM-UHFFFAOYSA-N |
Pubchem ID : | 10013210 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 64.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.4 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.98 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.44 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.31 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.75 |
Solubility | 0.0367 mg/ml ; 0.000178 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.44 |
Solubility | 0.0753 mg/ml ; 0.000365 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.95 |
Solubility | 0.00231 mg/ml ; 0.0000112 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
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) |
Yes |
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 |
-5.14 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 |
2.0 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) |
2.4 |
* 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 |
---|---|---|
71% | With niobium pentachloride; In dichloromethane; at 25℃; | General procedure: To a solution of CH2Cl2 (10.0 mL), NbCl5 (10.0 mol %) and ortho-alkynyl aldehydes (1 mmol), ethyl 2-diazoacetate (1.2 mmol) was added and the reaction mixture was allowed to stir at 25 C for 12-16 h. The reaction mixture was filtered and diluted with ethyl acetate and washed with brine solution. The combined organic fractions were dried over anhydrous Na2SO4 and concentrated under vacuum to yield the crude product. The crude product was purified by column chromatography on silica gel using ethyl acetate/hexane as the eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With copper (I) iodide; trans-bis(triphenylphosphine)palladium(II) dichloride; In triethylamine; at 60℃; for 4h;Inert atmosphere; | O-Bromobenzaldehyde (9.3g 50mmol), phenylacetylene (5.355g 52.5mmol) and 200ml triethylamine were injected into a 500ml Shrek tube under nitrogen conditions, and then bistriphenylphosphine palladium dichloride (0.702g1mmol) ) And cuprous iodide (0.190g 1mmol), stirred at 60C for 4h, passed silica gel column chromatography, eluent is petroleum ether: ethyl acetate = 50:1, to obtain 2-phenylynyl benzaldehyde (10.094g 98%) |
98% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; at 55℃;Inert atmosphere; | To a solution of 2-bromobenzaldehyde (1.85 g, 10.0 mmol) and ethynylbenzene (1.124g,11.0 mmol) in Et3N (20.0 mL) was added Pd(PPh3)2Cl2 (140 mg, 2.0% mol) and CuI (20 mg,1.0% mol). The mixture was stirred at 55 oC for overnight. It was then quenched with water andwashed with ethyl acetate. After removal of solvent, the crude residue was purified by flashchromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) to afford the desiredproduct 2-(phenylethynyl)benzaldehyde (2.02 g, 98% yield). |
95% | With copper (I) iodide; bis(benzonitrile)palladium(II) chloride; tri-tert-butyl phosphine; triethylamine; In toluene; at 20℃; for 8h;Inert atmosphere; | Sonogashira Cross Coupling of 2-bromobenzaldeyde with Phenylacetylene (B1) (0164) A suspension of aryl bromide (4.5 mmol), PdCl2(PhCN)2 (0.23 mmol), Cu(I) iodide (0.23 mmol) in 20 mL of triethylamine was degassed three times with freeze/pump/thaw technique in a flame dried round bottom flask. Once the reaction mixture was completely thawed and the atmosphere replaced with argon, tri-tert-butylphosphine (0.45 mmol in a 10% solution of toluene) was added, immediately followed by 1.2 equiv. of phenylacetylene (5.4 mmol) using a syringe. The mixture was allowed to react for 8 hours and monitored by TLC. After total consumption of the aryl bromide, the reaction mixture was filtered through celite and extracted with DCM (3×30 mL). The organic layer was washed with a saturated solution of ammonium chloride, water and dried over anhydrous Na2SO4. Solvent was removed under reduced pressure. The reaction mixture was purified by flash chromatography (eluent: hexane/ethyl acetate) on silica gel to afford compounds B1 (95%). |
95% | With copper (I) iodide; bis (triortho-tolylphosphine)palladium(II) chloride; In triethylamine; at 50℃; for 12h;Inert atmosphere; | General procedure: To a solution of o-bromobenzaldehyde (10.0 mmol, 1.85 g),PdCl2(PPh3)2 (0.2 mmol, 140.4 mg) and CuI (0.1 mmol, 19.0 mg) inEt3N (0.3 M) was added ethynylbenzene (12.0 mmol, 1.32 mL). Theobtained mixture was stirred for 12 h at 50C under argon atmosphere.Sat. aq. NH4Cl solution (15.0 mL) was added to the mixture, and the product was extracted with CHCl3 (15.0 mL 3). Theorganic layer was dried over Na2SO4 and filtered. After removal ofthe solvent under reduced pressure, the residue was purified bysilica-gel column chromatography (eluent: n-hexane:EtOAc 19:1)to give o-(phenylethynyl)benzaldehyde (1.96 g, 95%). To a solutionof o-(phenylethynyl)benzaldehyde in EtOH (1.0 M) was added hydroxylaminehydrochloride (1.2 equiv.). The mixture was stirred for1 h at room temperature. To the obtained mixture were slowlyadded Zn powder (2.5 equiv.) and hydrochloric acid (12.0 M, 4.0equiv.) at 0 C. The obtained mixture was stirred for 0.5 h at roomtemperature under argon atmosphere. A solution of ammonia(28e30%) was slowly added until pH S 7, and the product wasextracted with CHCl3 (15.0 mL 3). The organic layer was driedover Na2SO4 and filtered. After removal of the solvent underreduced pressure, p-toluenesulfonyl chloride (1.1 equiv.) and pyridine(0.5 M) were added to the residue in dichloromethane (1.0 M)at 0 C. The obtained mixture was stirred for 12 h at room temperatureunder argon atmosphere. Aq. NH4Cl solution (15.0 mL)was added to the mixture, and the product was extracted withCHCl3 (15.0 mL 3). Then, the organic layer was dried over Na2SO4and filtered. After removal of the solvent under reduced pressure,the residue was purified by silica-gel column chromatography(eluent: n-hexane:EtOAc 3:1) to give N-(o-phenylethynyl)benzylp-toluenesulfonamide 1A (2.76 g, 76%). Other N-(o-arylethynyl)benzyl p-toluenesulfonamides 1Be1W were obtained in 55%e78%yields by the same procedure. |
92% | With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; 1,1'-bis(diphenylphosphino)ferrocene; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran;Reflux; Inert atmosphere; | Tetrakis(triphenylphosphine)palladium (200 mg, 0.173 mmol), 1,1'-bis (diphenylphosphino)- ferrocene (448 mg, 0.808 mmol) and CuI (102 mg, 0.536 mmol) were added to a solution of 2-bromobenzaldehyde (625 μL, 5.35 mmol), ethynylbenzene (1.18 mL, 10.8 mmol) in dry THF (20 mL) and diisopropylethylamine (5 mL). After the reaction mixture was refluxed overnight under Ar, the filtrate through Celite was evaporated. The resulting residue was purified by column chromatography on silica gel (n-hexane/EtOAc = 20/1) provided the title compound (1015 mg, 4.92 mmol) in 92%yield as a brown oil. 1H NMR (400 MHz, CDCl3): δ 10.66 (s, 1H), 7.95 (dd, J = 7.6 Hz, 1.2 Hz, 1H), 7.65 (m, 1H), 7.61-7.55 (m, 3H), 7.46 (t, J = 7.2 Hz, 1H), 7.41-7.37 (m, 3H). |
~ 91% | With triethylamine;[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; at 50℃; for 5h; | About 10 mmols of 2-bromobenzaldehyde was put into a 100 mL two-neck round flask, and was dissolved in about 40 mL of Et3N. Then, about 1.2 mmols of phenylacetylene was added. After PdCl2(PPh3)2 (about 2 mol%) and CuI (about 1 mol%) were added, the temperature was increased. The solution was stirred at about 50C for about 5 hours. The reaction completion was confirmed using TLC. After the end point, the solution was cooled down to room temperature. Then, the solid was filtered, and solvent was removed under reduced pressure. Then, compound 11 was obtained in a form of about 91 % yellow oil using silica gel chromatography (EtOAc/Hex=1/10). Starting material, 2-(phenylethynyl)benzaldehyde (about 5.0 mmol) was put into a one neck round flask, and t-BuNH2 (about 6eq) was added. Then the solution was stirred at room temperature for about 24 hours. The end point was confirmed using TLC. Then, distillation under reduced pressure was performed. Next, the solution was washed with about 50 mL of EtOAc, dried with sodium sulfate anhydride, and filtered. Then, the impure compound 12 was obtained using distillation under reduced pressure. 1H NMR(CDCl3) δ 8.94(s, 1H), 8.12-8.05(m, 1H), 7.54-7.44(m, 3H), 7.33-7.25(m, 5H), 1.34(s, 9H);IR (CHCl3, cm-1) 3065, 2210, 1644 |
90% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; at 60℃; for 4h; | After introducing triethylamine (1500 ml) to 2-bromobenzaldehyde (150 g, 0.81 mol, 1 eq.), ethynylbenzene (99 g, 0.97 mol, 1.2 eq.), Pd(PPh3)2Cl2 (11.8 g, 0.016 mol, 0.02 eq.) and CuI (1.54 g, 0.008 mol, 0.01 eq.), the result was stirred for 4 hours at 60 C. Water was added thereto to terminate the reaction, and the result was extracted using MC and water. After that, water was removed using anhydrous Na2CO3. The result was separated using a silica gel column to obtain Compound 3-1 (150 g) in a 90% yield. |
89% | With tripotassium phosphate tribasic; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In toluene; at 120℃;Schlenk technique; Inert atmosphere; | General procedure: In an oven-dried Schlenk tube were added bromoarylcarbonyl 1/8 (100.0-204.8 mg, 0.54 mmol), phenylacetylene (110.2 mg, 1.08 mmol), Pd(OAc)2 (4.8 mg, 4 mol%), xantphos (25 mg, 8 mol%), and K3PO4 (458 mg, 2.16 mmol) followed by anhyd toluene (1.0 mL) at r.t. under N2 atmosphere and the reaction mixture was allowed to stir at 120 C for 2-6 h. Progress of the alkyne 2 and 9 formation was monitored by TLC until the reaction was complete. Then, the mixture was filtered through Celite and washed with CH2Cl2. Evaporation of the solvent under reduced pressure and purification of the crude material by silica gel column chromatography (PE/EtOAc) furnished the alkyne 2 and 9 (72-91%), respectively, as viscous liquid/semi-solid. |
89% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; at 50℃; for 12h;Inert atmosphere; | Under nitrogen conditions, 2-bromobenzaldehyde(10 mmol), phenylacetylene (12 mmol), Pd(PPh3)2Cl2(0.2 mmol) and CuI (0.1 mmol) were successively introducedinto a 100-mL two-neck flask equipped with Et3N(40 mL). The resulting mixture was stirred at 50 C for 12 hand monitored with TLC. After completion, the crude mixturewas filtered through celite and Et3Nwas removed undervacuum. The residue was diluted with EtOAc (60 mL) andwashed with water (2 × 50 mL). The organic layer was driedover Na2SO4,which was further purified via column chromatographyon silica gel (the mixture of petroleum ether andEtOAc was used as elute) to give 2-(phenylethynyl)benzaldehyde(1.83 g) in 89% yield. 2-(phenylethynyl)benzaldehyde was dissolved in methanol(30 mL), and the resulting mixture was cooled to 0 C. NaBH4 (5 mmol) was added in portions, and the solutionwas stirred for additional 20 min. The reaction was quenchedwith saturated ammonium chloride solution (30 mL).Methanol was removed under vacuum, and the residue wasextracted by EtOAc (2 × 30 mL). The combined organic layerwas dried over anhydrous Na2SO4.After the solvent wasremoved under reduced pressure, (2-(phenylethynyl)phenyl)methanol 1a was obtained (1.76 g) in 95% yield, which wasused directly for the next cyclization without purification. |
87% | With piperidine; In neat (no solvent); at 90℃; for 5h;Green chemistry; | General procedure: Aryl halide (1 mmol), alkyne (1.1 mmol), piperidine (2 mmol)and the Fe3O4(at)SiO2-NHC-Pd() catalyst (0.007 g, 0.43 mol%) wasstirred at 90 C for the appropriate time as indicated in Table 5 andreaction progress was confirmed by TLC. After completion of thereaction, the reaction mixture was diluted with ethyl acetate(10 mL) and the catalyst was separated with an external magnet.Solvent was evaporated under reduced pressure and the cruderesidue was then purified by column chromatography using ethylacetate/hexane as an eluent to give the desired Sonogashira product(5a-5ak; Table 5). |
85% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; at 50℃; for 10h;Inert atmosphere; | (1)Add phenylacetylene (1.32 g, 3.0 mmol) to a solution of 2-bromobenzaldehyde (2 g, 10.8 mmol) in triethylamine (25 mL).Pd(PPh3)2Cl2 (152 mg, 216 μmol),CuI (41 mg, 216 μmol).After argon gas protection, heating at 50 C for 10 h,Triethylamine was removed under reduced pressure. The residue was extracted with ethyl acetate (20 mL×3).Then use water (10mL)Wash twice with saturated saline (10 mL).Dry over anhydrous sodium sulfate, filter, and remove the solvent under pressure.Silica gel column chromatography(The eluent is petroleum ether / ethyl acetate = 20/1)Purified to obtain a yellow liquid 12c,2-(phenylethynyl)benzaldehyde(1.9 g, 85% yield). |
84% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; at 20℃; for 12h;Inert atmosphere; | a) Synthesis of 2-(phenylethynyl)benzaldehyde (S-1) 2-bromobenzaldehyde (1.00 g, 5.43 mmol) was added in one portion to a solution of CuI (0.10 g, 10 mol %) in Et3N (30 mL) and degassed with nitrogen for 15 min at 23 C. PdCl2(PPh3)2 (0.32 g, 5 mol %) was added to the mixture and was stirred for 15 min before being treated with ethynylbenzene (0.63 g, 6.2 mmol) dropwise. The resulting solution was stirred at room temperature for 12 h and then filtered through a celite pad, concentrated, and eluted through a silica column to give the desired 2-(phenylethynyl)benzaldehyde (S-1) (0.93 g, 4.5 mmol, 84%). |
82% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; In triethylamine; at 50℃; for 3h; | After 1 g (5,4 mmol) of Compound SM and 662 mg (6.48 mmol) of ethynylbenzene were dissolved in 22 ml of TEA, 10.3 mg (0.05 mmol) of CuI and 701.9 mg (0.1 mmol) of (Ph3P)2PdCl2 were added dropwise thereto. The mixture was stirred for 3 hours at 50C. After the reaction completed, the result was extracted with ethyl acetate (EA) and water, and the EA layer was washed with 1N-HCl. The organic layer was dried using anhydrous sodium sulfate and filtered, and after the solvent was removed by vacuum distillation again, the result was separated and purified using column chromatography, and 913 mg (82%) of target Compound 1-18 was obtained. |
79% | With copper (I) iodide; C26H24N6NiS4; triethylamine; In N,N-dimethyl-formamide; at 80℃; for 8h;Inert atmosphere; | General procedure: In an oven-dried round bottom flask under an atmosphere of N2, a mixture of aryl halide (1 mmol), phenylacetylene (1.5 mmol), 1 (60.75 ppm or 0.05 mol%), copper(I) iodide (5 mmol), and Et3N (3.0 mmol) in DMF (5 mL) was taken. The reaction mixture was stirred 80 C for 2 h. At the end of the mentioned time, the reaction mixture was diluted with EtOAc (20 mL), washed with water (3 x 10 mL). The combinedorganic layer was dried over anhydrous Na2SO4, filtered and stripped off the solvent under reduced pressure. The residue was subjected to column chromatography on silica gel using ethyl acetate and n-hexane mixtures to afford the desired product in high purity. The products were characterized by 1H and 13C NMR analysis. The procedure for the Sonogashira reaction of aryl bromides was similar as mentioned above in the case of aryl iodides, where aryl bromide (1 mmol) and 1 (121.5ppm or 0.1 mol %) were used and the reaction was carried out for 8 h. |
79% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; at 50℃; for 24h;Inert atmosphere; Schlenk technique; | Compound 2: An oven-dried Schlenk tube was charged with 2-bromobenzaldehyde (0.31mL, 2.7 mmol), phenylacetylene (0.31 mL, 2.8 mmol), copper iodide (10.5 mg, 0.054 mmol), and bis(triphenylphosphine)palladium chloride (38 mg, 0.054 mmol). The mixture was degassed and flushed with argon for three times, then triethylamine (5 mL) was added and the resulting mixture was stirred at 50 C for 24 h. After cooling to room temperature, the slurry was taken up in dichloromethane (50 mL) and water (20 mL). The aqueous layer was extracted with CH2Cl2 (2 × 20 mL). The combined organic layers were dried over magnesium sulfate, then concentrated and purified by column chromatography on silica gel (eluent: petrol ether/ethyl acetate = 75:1) to afford product 2 (438 mg, 79% yield) as reddish oil. |
78% | With C37H29ClN3PPdS; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;Catalytic behavior; | General procedure: In an oven-dried round bottom flask, a mixture of aryl halide (1 mmol), phenylacetylene (1.5 mmol), complex 1 (0.5 mol % for aryl bromides, 1.0 mol % for aryl chlorides) and Et3N (3.0 mmol) in DMF (5 mL) was taken. The reaction mixture was stirred at room temperature (12 h for aryl bromides, 24 h for aryl chlorides). At the end of the time period mentioned, the reaction mixture was diluted with EtOAc (20 mL) and washed with water (3 x 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and stripped off the solvent under reduced pressure. The residue was subjected to column chromatography on silica gel using ethyl acetate and n-hexane mixtures to afford the desired product in high purity. The products were characterized by 1H and 13C NMR analysis. |
38% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; at 20℃; | To a solution of 2-bromobenzaldehyde (6.68 g, 36.1 mmol, 1.0 equiv.), PdC (PPh3)2 (512 mg, 729 μιηοΙ, 4 mol%) and Cul (280 mg, 1.47 mmol, 2 mol%) in degassed NEt3 (70 ml_) was added phenylacetylene (4.41 g, 43.2 mmol, 1.3 equiv.). After the reaction was stirred at room temperature over night the solvent was removed under reduced pressure. The crude material was purified by flash column chromatography (S1O2; petrolether : ethylacetate = 20:1 ) to afford the title compound 1d as slightly yellow oil (2.84 g, 13.8 mmol, 38%). |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; In tetrahydrofuran; at 50℃; for 4h;Inert atmosphere; | General procedure: A two-necked dry flask was charged with the ortho-bromobenzaldehyde (10 mmol), the ethynylbenzene (1.22 g, 12 mmol), and freshly distilled THF 20 mL. Then Et3N (2.8 mL, 20 mmol, 2.0 equiv), PdCl2(PPh3)2 (210 mg, 0.36 mmol, 0.03 equiv), and CuI (95.2 mg, 0.6 mmol, 0.05 equiv) were added. The mixture was heated at 50 C for 4 h. After the reaction was complete (monitored by TLC), the solvents were evaporated under reduced pressure. The crude product was purified by column chromatography (SiO2, ethyl acetate/petroleum ether = 100: 1) to afford the ortho-alkynylbenzaldehyde. | |
With copper (I) iodide; cis-dichlorobis(triphenylphosphine) palladium(II); triethylamine; In tetrahydrofuran;Inert atmosphere; Reflux; | (1) intermediate compound 3a-3i synthesis:Taking 1mmol compound 1a-1c, compound 1mmol 2a-2c, 0 . 1mmol CuI of, 0.03mmol the Pd (PPh3)2Cl2and 2mmol triethylamine dissolved in 5 ml of tetrahydrofuran, under the protection of nitrogen, heating to reflux, TLC monitoring of the reaction process, the reaction is complete, the reactant is cooled to room temperature, by adding a proper amount of water, and then divide the liquid extraction, drying, then column chromatography, to obtain compound 3a-3i (the 1 to 2-bromophenylacetic formaldehyde or 2-bromo-5-methyl-phenyl-formaldehyde or 2-bromo-5-chlorobenzene formaldehyde, 2 for phenylacetylene or the methyl acetylene or to paradichlorbenzene acetylene, thus 1a-1c and 2a-2c intermediate obtained by reaction of a compound 9 a). | |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; In tetrahydrofuran;Inert atmosphere; Reflux; | 1 mmol of the compound 1, 1 mmol of the compound 2, 0.15 mmol of CuI, 0.06 mmolOf Pd (PPh3) 2Cl2 and 2 mmol of triethylamine were dissolved in 5 mL of tetrahydrofuran under nitrogen,Heat reflux, TLC monitoring reaction process, until the reaction is complete, the reaction is cooled to room temperature, adding the right amount ofWater, and then fractional extraction, drying, and then column chromatography, compounds 3a-3l. | |
With quinoline; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | Referring to Chemistry-A European Journal, 2007, 13(19), 5632, 2-bromobenzaldehyde (1 eq, CAS No. 6630-33-7), CuI (0.025 eq), Pd(PPh3)2Cl2 (0.05 eq), Et3N (0.6 ml), and the ethynylbenzene (1.2 eq, CAS No. 536-74-3) were added under argon to a stirred solution of quinoline (1 mmol) in anhydrous DMF (1.0M to 2-bromobenzaldehyde). The mixture was stirred at room temperature and monitored by thin layer chromatography (TLC). After evaporation under vacuum, the crude mixture was purified by column chromatography on silica gel to give o-(phenylethynyl)benzaldehyde. | |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; In N,N-dimethyl-formamide;Inert atmosphere; | General procedure: A mixture of 2-bromobenzaldehyde (1mmol), CuI (2 mol%) and Pd(PPh3)2Cl2 (2 mol%) in DMF (5 mL)was degassed for 5 min under N2 atmosphere. Then the corresponding alkyne (1.5 equiv) along with 2mL of triethylamine was added to this mixture and allowed to stir at room temperature under N2atmosphere for 2 h. After completion of the reaction indicated by TLC, 5,6-diamino-1,3-dimetyluracilhydrate (1 mmol) and additional (2 mol%) CuI was added to this mixture in the same reaction vessel.Then the mixture was allowed to reflux for 3-4 h at 120 C in open air and progress of the reaction wasmonitored by TLC. After completion of the reaction, solvent was removed under reduced pressure. Theorganic layer extracted with EtOAc (3 × 10 mL) and washed with brine water, dried over Na2SO4. Theorganic extract was concentrated under reduced pressure. The crude product was purified by columnchromatography with EtOAc: petroleum ether (3:7) as eluent to get the desired compound. | |
With copper (I) iodide; (3-carboxyphenyl)diphenylphosphine; palladium diacetate; potassium carbonate; In tetrahydrofuran; lithium hydroxide monohydrate; at 50℃; for 2h;Green chemistry;Catalytic behavior; | In a 10 mL round bottom flask containing 2 mL of (1 : 4) THF-H2O, Pd(OAc)2 (0.02 mmol), 3-(diphenylphosphino)benzoic acid (L 4 ), (0.04 mmol), CuI (0.05 mmol), 2-bromo benzaldehyde (1 mmol), phenylacetylene (1.2 mmol). K2CO3 (2 mmol), were added and the reaction mixture was stirred at 50 C for 2 h until the completion of the starting materials as monitored by TLC. Then NH4OAc (1.5 mmol) was added and again the whole reaction mixture was stirred at same temperature for additional 2 hours. After the formation of desired product 4a as confirmed by TLC, the reaction mixture was extracted with ethyl acetate (10 mL) and water (10 mL) and the organic layer was washed with aqueous saturated brine solution and dried over Na2SO4. The solvent was removed under vacuum, and the residue was purified by flash column chromatography on silica gel using ethyl acetate/ hexanes as the eluent to afford the desired product 4a. | |
With quinoline; copper (I) iodide; trans-bis(triphenylphosphine)palladium(II) dichloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | Referering Chemistry-A European Journal, 2007, 13(19), 5632, 2-bromo-benzaldehyde (1 eq, CAS No.6630-33-7), CuI (0.025 eq), Pd(PPh3)2Cl2 (0.05 eq), Et3N (0.6 ml) and ethynyl benzene (1.2 eq, CAS No. 536-74-3), under argon was added to a stirred solution of quinoline (1 mmol) in anhydrous DMF (1.0 M in 2-bromobenzaldehyde). The mixture was stirred at room temperature, and monitored by thin layer chromatography (TLC). After evaporation in vacuo, the crude mixture was purified by column chromatography on silica gel, o-(phenylethynyl) benzaldehyde was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | In ethanol; at 20℃; for 1h; | Compound 3-1 (155 g, 0.75 mol, 1 eq.) and TsNHNH2 (168 g, 0.90 mol, 1.2 eq.) were introduced to EtOH (3100 ml), and the result was stirred for 1 hour at room temperature (R.T). Produced solids were filtered and dried to obtain Compound 3-2 (150 g) in a 53% yield. |
In dichloromethane; at 20℃; for 0.5h; | General procedure: A mixture of 2-alkynylbenzaldehyde 1 (0.20 mmol) and 4-methylbenzenesulfonohydrazide (0.24 mmol, 1.2 equiv) in anhydrous dichloromethane (0.5 mL) was stirred at room temperature for half an hour. Then bromine (0.24 mmol, 1.2 equiv) and DABCO (0.24 mmol, 1.2 equiv) were added. After stirred at room temperature for 10 min, carbodiimide 2 (0.40 mmol, 2.0 equiv) in anhydrous acetonitrile (1.0 mL) was added. After completion of reaction as indicated by TLC, the reaction was quenched with a saturated NH4Cl solution (3.0 mL). The mixture was stirred for an additional 10 min and extracted with EtOAc (3.0 mL×3). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuum. The crude residue was purified by flash column chromatography (EtOAc/n-hexane, 1:4) to give the desired 1-(4-bromoisoquinolin-1-yl)guanidine 3. | |
With hydrogenchloride; In ethanol; at 20℃; | (2) intermediate compound 4a-4i synthesis:The 5mmol compound 3a-3i and 5mmol paratoluene sulfonyl hydrazide in 40 in anhydrous ethanol, dropping a drop of concentrated hydrochloric acid, stirred at a room temperature, the reaction is finished after a plurality of solid precipitation, filtration, the solid is recrystallized with ethanol, can be with high yield intermediate 4a-4i. |
With hydrogenchloride; In ethanol; at 20℃; | General procedure: The 5mmol compound 3a-3i and 5mmol para-toluenesulfonyl chloride 40 in anhydrous ethanol, dropping a drop of concentrated hydrochloric acid, stirred at a room temperature, the reaction is finished after a plurality of solid precipitation, filtration, the solid is recrystallized with ethanol, can be with high yield intermediate 4a-4i. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | a) Synthesis of 1-(2-(phenylethynyl)phenyl)-3-(trimethylsilyl)prop-2-yn-1-ol (S-5) A THF solution of ethynyltrimethylsilane (0.77 g, 7.8 mmol) was cooled to -78 C. n-BuLi (2.5 M in hexane, 3.1 mL, 7.8 mmol) was slowly added to this solution and was stirred for 0.5 h at -78 C. <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> (S-1) (1.32 g, 6.40 mmol) was added to the resulting solution and was stirred for 1 h at -78 C. The reaction was quenched with water (15 mL) and extracted with ethyl acetate (60 mL). The extract was washed with brine solution, dried over Na2SO4, and concentrated under reduced pressure. The residue was eluted through a silica column to afford 1-(2-(phenylethynyl)phenyl)-3-(trimethylsilyl)prop-2-yn-1-ol (S-5) (0.95 g, 3.1 mmol, 49%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In tetrahydrofuran; at 0 - 20℃; for 2h; | 2-Phenynylbenzaldehyde (10.094g 49mmol) and 50ml of anhydrous tetrahydrofuran were added to a 500ml round-bottomed flask and stirred at 0C. Slowly added 150ml of ethynylmagnesium bromide tetrahydrofuran solution (0.5mol/L), and after the addition, stirred at room temperature for 2h . Quench with saturated ammonium chloride solution, extract with ethyl acetate, dry with anhydrous magnesium sulfate,It was concentrated to obtain 1,6-diynol (10.564g 98%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium tetrahydroborate; In methanol; at 0℃; for 0.5h; | General procedure: NaBH4 (50 mg, 1.3 mmol) was added to a solution of commercial 2-phenoxybenzaldehyde (260 mg, 1.31 mmol) in MeOH (5 mL) at 0 C. After stirring for 30 min at 0 C, the reaction mixture was diluted with water, extracted with EtOAc, dried over MgSO4 and evaporated. The resulting residue was purified by column chromatography on silica gel (n-hexane/EtOAc = 5/1) to provide the title compound (228 mg, 1.14 mmol) in 87% yield as a colorless solid. |
95% | With sodium tetrahydroborate; In methanol; at 0℃; for 0.333333h; | Under nitrogen conditions, 2-bromobenzaldehyde(10 mmol), phenylacetylene (12 mmol), Pd(PPh3)2Cl2(0.2 mmol) and CuI (0.1 mmol) were successively introducedinto a 100-mL two-neck flask equipped with Et3N(40 mL). The resulting mixture was stirred at 50 C for 12 hand monitored with TLC. After completion, the crude mixturewas filtered through celite and Et3Nwas removed undervacuum. The residue was diluted with EtOAc (60 mL) andwashed with water (2 × 50 mL). The organic layer was driedover Na2SO4,which was further purified via column chromatographyon silica gel (the mixture of petroleum ether andEtOAc was used as elute) to give <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong>(1.83 g) in 89% yield. <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> was dissolved in methanol(30 mL), and the resulting mixture was cooled to 0 C. NaBH4 (5 mmol) was added in portions, and the solutionwas stirred for additional 20 min. The reaction was quenchedwith saturated ammonium chloride solution (30 mL).Methanol was removed under vacuum, and the residue wasextracted by EtOAc (2 × 30 mL). The combined organic layerwas dried over anhydrous Na2SO4.After the solvent wasremoved under reduced pressure, (2-(phenylethynyl)phenyl)methanol 1a was obtained (1.76 g) in 95% yield, which wasused directly for the next cyclization without purification. |
88% | With sodium tetrahydroborate; In methanol; at 0 - 20℃; | General procedure: To a solution of o-alkynyl quinoline aldehydes 2 (1 mmol) or o-alkynyl benzaldehyde 4 in methanol (5 mL) at 0 C was added NaBH4 (2 equiv) slowly over a period of time. After whole of NaBH4 had been added, the reaction mixture was stirred at room temperature. After completion of reaction (monitored by TLC), chilled water was added and solid precipitate was obtained. The solid precipitate was filtered and used as such. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With 4-aminomethylphenol; silver nitrate; In ethanol; at 80℃; | 1 mmol of compound 1a, 1.5 mmol of p-hydroxybenzylamine and 1.0 mmol of silver nitrate were dissolved in ethanol, and the reaction was stirred at 80 C. The reaction was monitored by TLC, the reaction was completed, the reaction was stopped, and the reaction was cooled to room temperature. The solvent was removed by steaming under reduced pressure.The residue is subjected to column chromatography to obtain the target product 2a.The yield was 78% |
69% | With ammonium hydroxide; In water; at 100℃; for 24h;Green chemistry; | General procedure: 2-(Phenylethynyl)benzaldehyde 1a (62.0 mg, 0.3 mmol) and ammonium hydroxide (1 mL) were added into a sealed tube. The mixture was stirred at 100 oC for 24h. After cooled to room temperature, 5 mL water was added. The mixture was extracted with ethyl acetate(10 mL×2). The combined organic phase was dried over anhydrous Na2SO4 for 1h. Next, the solvent was removed under reduced pressure. The crude product was purified by column chromatography to afford the corresponding isoquinoline 2a. |
63% | With 4-aminomethylphenol; silver nitrate; In ethanol; at 80℃; for 12h; | General procedure: To a solution of <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> 1a (62.0 mg, 0.3 mmol) in EtOH (2 mL) was added 4-hydroxybenyzlamine (36.9 mg, 0.3 mmol) and AgNO3 (51.0 mg, 0.3 mmol). The mixture was stirred at 80 C for 12h. Then the reaction was quenched with water, extracted with DCM, dried with anhydrous Na2SO4. The solvent was removed under reduced pressure to afford crude product. Purification furnished the corresponding isoquinoline 3a. |
57% | With ammonium bicarbonate; silver nitrate; In acetonitrile; at 100℃; | 1 mmol of compound 3, 3 mmol of ammonium bicarbonate and 0.3 mmol of silver nitrate were dissolved in acetonitrile, 100 C stirring reaction, TLC monitoring reaction process, until the reaction is complete, stop the reaction, the reactantAfter cooling to room temperature, the solvent was removed by distillation under reduced pressure and the residue was subjected to column chromatography to give the target compound of formula I. |
49% | With trifluorormethanesulfonic acid; ammonium carbonate; In toluene; at 120℃; for 12h;Inert atmosphere; | The reaction is carried out in a reactor. The reactor is evacuated and replaced with argon.2-alkynylbenzaldehyde 1 (0.3 mmol) and ammonium carbonate (3-fold molar amount of 2-alkynylbenzaldehyde 1) were added,Toluene (3 mL) was then added, trifluoromethanesulfonic acid (10 mmol%) was added, and the reaction was carried out at 120C for 12 hours.After the reaction was completed, the solvent was removed and the solid was dissolved in dichloromethane and subjected to silica gel column chromatography.Isoquinoline 2 derivatives are available. |
With copper(l) iodide; ammonium acetate; In tetrahydrofuran; water; at 50℃; for 2h;Green chemistry;Catalytic behavior; | In a 10 mL round bottom flask containing 2 mL of (1 : 4) THF-H2O, Pd(OAc)2 (0.02 mmol), 3-(diphenylphosphino)benzoic acid (L 4 ), (0.04 mmol), CuI (0.05 mmol), 2-bromo benzaldehyde (1 mmol), phenylacetylene (1.2 mmol). K2CO3 (2 mmol), were added and the reaction mixture was stirred at 50 C for 2 h until the completion of the starting materials as monitored by TLC. Then NH4OAc (1.5 mmol) was added and again the whole reaction mixture was stirred at same temperature for additional 2 hours. After the formation of desired product 4a as confirmed by TLC, the reaction mixture was extracted with ethyl acetate (10 mL) and water (10 mL) and the organic layer was washed with aqueous saturated brine solution and dried over Na2SO4. The solvent was removed under vacuum, and the residue was purified by flash column chromatography on silica gel using ethyl acetate/ hexanes as the eluent to afford the desired product 4a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | at 20℃; for 12h; | (2)To 11c (2.0g, 12.1mmol)Triethylamine (25mL)Iodobenzene (2.96 g, 14.5 mmol) was added to the solution.Pd(PPh3)2Cl2 (170 mg, 241 μmol),CuI (46 mg, 241 μmol).Under argon protection conditions,After the reaction was carried out for 10 hours,Triethylamine was removed under reduced pressure.The residue was extracted with ethyl acetate (20 mL×3).Then water (10 mL) and saturated brine(10 mL) was washed twice, dried over anhydrous sodium sulfate and filtered.The solvent was removed under pressure.The residue was purified by silica gel column chromatography eluting elutObtaining a yellow liquid 11b,4-methyl-N-(3-phenylpropyl-2-alkyne)aniline(2.6 g, 89% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With C58H44Ag2F6O6S6; In dichloromethane; at 20℃; for 12h;Inert atmosphere; Schlenk technique; | General procedure: A dried Schlenk tube was charged with the silver salt (0.5 mmol%-5 mol %), then degassed and backfilled with argon for three times. A solution of alkyne 2 (30 mg, 0.15 mmol) in anhydrous CH2Cl2 (1 mL) and MeOH (18 μL, 0.45 mmol) was added and the mixture was stirred at room temperature for 12 h. The crude solution was concentrated under reduced pressure and purified by column chromatography on silica gel (eluent: petrol ether/ ethylacetate = 50:1) to obtain product 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; at 20℃; for 24h; | About 10 mmols of 2-bromobenzaldehyde was put into a 100 mL two-neck round flask, and was dissolved in about 40 mL of Et3N. Then, about 1.2 mmols of phenylacetylene was added. After PdCl2(PPh3)2 (about 2 mol%) and CuI (about 1 mol%) were added, the temperature was increased. The solution was stirred at about 50C for about 5 hours. The reaction completion was confirmed using TLC. After the end point, the solution was cooled down to room temperature. Then, the solid was filtered, and solvent was removed under reduced pressure. Then, compound 11 was obtained in a form of about 91 % yellow oil using silica gel chromatography (EtOAc/Hex=1/10). Starting material, <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> (about 5.0 mmol) was put into a one neck round flask, and t-BuNH2 (about 6eq) was added. Then the solution was stirred at room temperature for about 24 hours. The end point was confirmed using TLC. Then, distillation under reduced pressure was performed. Next, the solution was washed with about 50 mL of EtOAc, dried with sodium sulfate anhydride, and filtered. Then, the impure compound 12 was obtained using distillation under reduced pressure. 1H NMR(CDCl3) δ 8.94(s, 1H), 8.12-8.05(m, 1H), 7.54-7.44(m, 3H), 7.33-7.25(m, 5H), 1.34(s, 9H);IR (CHCl3, cm-1) 3065, 2210, 1644 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With toluene-4-sulfonic acid; In 1,2-dichloro-ethane; at 200℃; for 0.5h;Microwave irradiation; | General procedure: A solution of <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> (1) (0.60 mmol, 124 mg), alkyne 2 (0.30 mmol), and TsOH.H2O(0.90 mmol, 171 mg) in ClCH2CH2Cl (2.0 mL) was treated at 200 Cfor 30 min under microwave condition (Biotage INITIATOR; Allreactions were carried out under temperature-constant operation). Thereaction mixture was diluted with CHCl3 and washed with saturatedNaHCO3 (aq) and brine. The organic layer was dried over MgSO4.After removal of the solvent under reduced pressure, the residue waspurified by chromatography on SiO2 to give the naphthalene derivatives. Further purification was carried out a recyclable preparativeHPLC, if necessary. The structures of the products were assigned bytheir NMR spectra. The product was characterized by comparing itsspectral data with previous report.8a |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With toluene-4-sulfonic acid; In 1,2-dichloro-ethane; at 200℃; for 0.5h;Microwave irradiation; | General procedure: A solution of <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> (1) (0.60 mmol, 124 mg), alkyne 2 (0.30 mmol), and TsOH.H2O(0.90 mmol, 171 mg) in ClCH2CH2Cl (2.0 mL) was treated at 200 Cfor 30 min under microwave condition (Biotage INITIATOR; Allreactions were carried out under temperature-constant operation). Thereaction mixture was diluted with CHCl3 and washed with saturatedNaHCO3 (aq) and brine. The organic layer was dried over MgSO4.After removal of the solvent under reduced pressure, the residue waspurified by chromatography on SiO2 to give the naphthalene derivatives. Further purification was carried out a recyclable preparativeHPLC, if necessary. The structures of the products were assigned bytheir NMR spectra. The product was characterized by comparing itsspectral data with previous report.8a |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With Difluoroacetic acid; copper(II) bis(trifluoromethanesulfonate); In 1,2-dichloro-ethane; at 100℃; for 0.25h;Inert atmosphere; | Referring to Journal of the American Chemical Society, 2003, 125(36), 10921, a mixture of <strong>[59046-72-9]o-(phenylethynyl)benzaldehyde</strong> (0.5 mmol, CAS No. 59046-72-9) and Cu(OTf)2(5 mol %) in 1,2-dichloroethane (2 ml) were added with (bromoethynyl)benzene (0.6 mmol, CAS No. 932-87-6) and CF2HCO2H (0.5 mmol) successively at room temperature under N2 atmosphere. The resulting mixture was stirred at 100 C. for 15 min and then cooled to room temperature. A saturated aqueous solution of NaHCO3 was added, and the mixture was extracted with ether three times. The combined extracts were washed with brine, dried over MgSO4, and evaporated to leave the crude product, which was purified by silica gel column chromatography using hexane as eluent to give 2-bromo-3-phenylnaphthalene (0.43 mmol) in 86% yield. |
86% | With Difluoroacetic acid; copper(II) bis(trifluoromethanesulfonate); In 1,2-dichloro-ethane; at 100℃; for 0.25h;Inert atmosphere; | Referring Journal of the American Chemical Society, 2003, 125(36), 10921, To a mixture of <strong>[59046-72-9]o-(phenylethynyl)benzaldehyde</strong> (0.5 mmol, CAS No. 59046-72-9) and Cu(OTf)2 (5 mol%) in 1,2-dichloroethane (2 ml), (bromoethynyl)benzene (0.6 mmol, CAS No. 932-87-6) and CF2HCO2H (0.5 mmol) were successively added at room temperature under an atmosphere of N2. Stirring the resulting mixture at 100 15 minutes and then cooled to room temperature. A saturated aqueous NaHCO3 solution was added and the mixture was extracted three times with ether. Combined extracts were rinsed with Breen, followed by drying and evaporation over MgSO4, by using hexane as an eluent was purified by silica gel column chromatography to give 2-bromo-3-phenyl-naphthalene (0.43 mmol) to yield 86%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With toluene-4-sulfonic acid; In 1,2-dichloro-ethane; at 200℃; for 0.5h;Microwave irradiation; | General procedure: A solution of <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> (1) (0.60 mmol, 124 mg), alkyne 2 (0.30 mmol), and TsOH.H2O(0.90 mmol, 171 mg) in ClCH2CH2Cl (2.0 mL) was treated at 200 Cfor 30 min under microwave condition (Biotage INITIATOR; Allreactions were carried out under temperature-constant operation). Thereaction mixture was diluted with CHCl3 and washed with saturatedNaHCO3 (aq) and brine. The organic layer was dried over MgSO4.After removal of the solvent under reduced pressure, the residue waspurified by chromatography on SiO2 to give the naphthalene derivatives. Further purification was carried out a recyclable preparativeHPLC, if necessary. The structures of the products were assigned bytheir NMR spectra. The product was characterized by comparing itsspectral data with previous report.8a |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With nickel(II) ferrite; potassium carbonate; In water; at 100℃; for 4h; | General procedure: In a round-bottom flask equipped with a condenser for refluxingand a magnetic stirring bar, aryl/alkyl halide (1 mmol), phenylacetylene (1 mmol), K2CO3 (1.1 mmol), nickel ferrite nanoparticles(0.05 mmol) and water (3 ml) were added and heated at 100 Cunder air atmosphere. The mixture was vigorously stirred underthese reaction conditions and its completion was monitored byTLC (EtOAc-n-hexane, 25:75).In each case, after completion of the reaction, the mixturewas dilutedwith diethyl ether and water. The organic layer was washed withbrine, dried over MgSO4, and concentrated under reduced pressureusing a rotary evaporator. The residue was purified by recrystallizationfrom ethanol and water. |
54% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 22h;Green chemistry; | General procedure: A mixture of aryl halide (1mmol), terminal alkyne (1mmol), K2CO3 (2mmol) and MNPFemTriazNHCAg complex (6) (100mg) in DMF (5mL) was stirred at 100C. The progress of reaction was monitored by TLC. After completion, the reaction mixture was quenched in ice cold water and 6 was separated by external magnet. The reaction mixture was extracted with ethyl acetate (3×25mL). Evaporation of solvent in vaccuo followed by column chromatography over silica gel using petroleum ether/ethyl acetate afforded desired Sonogashira coupling products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With indium; In N,N-dimethyl-formamide; at 20℃; | General procedure: Indium metal (2.5mmol) and allyl bromide (3mmol) were added to a solution of o-alkynyl quinoline aldehydes 2 (1mmol) in DMF (8mL) and stirred for 2-4h. After completion of the reaction, the reaction mixture was quenched with a few drops of 2N HCl, diluted with water and the corresponding 1-(2-arylalkynylquinolin-3-yl)-but-3-en-1-ols (3) precipitated out. The solid precipitates were filtered out and were pure enough for further use. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With copper(I) trifluoromethanesolfonate toluene complex; In dichloromethane; at 60℃; for 10h;Molecular sieve; | 0.412g (2 mmol) 2-phenylethynylbenzaldehyde [using orthobromobenzaldehyde and phenylacetylene as raw materials,Preparation according to J. Org. Chem., 2014, 79(9), 4231-4239], 0.257 g (2.4 mmol) 4-methylaniline,0.306 g (3 mmol) phenylacetylene, 0.104 g (0.2 mmol) copper triflate toluene complex, 0.5 g 4Å-MS and 15 mlA mixture of dichloromethane was reacted at 60C for 10 h. . It was filtered off, evaporated to dryness and purified by silica gel column chromatography (PE:EA=9:1).The target compound 1-phenylethynyl-2-(4-methylphenyl)-3-phenyl-1,2-dihydroisoquinoline 0.70 g (light yellow solid,The rate is 88%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine; In water; at 20℃; for 8h; | General procedure: An aryl halide (1.0 mmol) and a terminal alkyne (1.2 mmol) were added to a mixture of PS-tsu-Pd(II) complex (3) (0.001 mmol), triethylamine (2.0 mmol), and water (3 mL) in a round bottom flask under vigorous stirring. The mixture was stirred at room temperature for 8 h under aerobic conditions. After completion of the reaction, the mixture was filtered to recover the catalyst. The polymer was washed with water, acetonitrile and subjected to vacuum drying for the next run. Further, the reaction mixture was extracted with ethyl acetate and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel using ethyl acetate/hexane as the eluent to give the corresponding coupling products. |
66% | With cetyltrimethylammonim bromide; potassium carbonate; In water; at 110℃; for 10h; | General procedure: In a typical reaction, a mixture of aryl halides (1.2 mmol), phenylacetylene (1.5 mmol), K2CO3 (276 mg, 2 mmol), cetyltrimethylammonium bromide (36 mg, 0.1 mmol), H2O (3 mL) and catalyst 3 (30 mg, 0.03 mmol of Cu) was stirred at 110 C for 10 h, then cooled to room temperature, filtered and washed with ethyl acetate (3 × 10 mL). The combined organic layers were extracted with water, saturated brine solution, and dried over anhydrous Na2SO4. The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography by using ethyl acetate/hexane (1:9) as eluent to give the corresponding product. All the products were confirmed by 1H, 13C NMR, and mass spectroscopic analysis. See the Supporting Information for full details. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With N-chloro-succinimide; copper(II) bis(trifluoromethanesulfonate); In 1,2-dichloro-ethane; at 80℃; for 8h;Inert atmosphere; | General procedure: A solution of <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> (1) (0.90 mmol, 0.185 g), alkyne (0.60 mmol), Cu(OTf)2 (0.045 mmol, 0.016 g), NXS (NBS, NCS, or NIS; 0.90 mmol) in ClCH2CH2Cl (4.0 mL) was stirred at 80 C for 8 h under a nitrogen atmosphere. The reaction mixture was diluted with CHCl3 and washed with saturated NaHCO3 aq. and brine. The organic layer was dried over MgSO4. After removal of the solvent under reduced pressure, the residue was purified by chromatography on SiO2 to give the 1-halonaphthalenes 3. Further purification was carried out a recyclable preparative HPLC, if necessary. |
Yield | Reaction Conditions | Operation in experiment |
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81% | With nickel(II) (2-((3-methylthiophen-2-yl)methylene)hydrazinecarbothioamide)2.; 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 100℃; for 5h; | General procedure: In an oven-dried round-bottom flask, a mixture of arylboronic acid (1.0 mmol), phenylacetylene (1.2 mmol), complex 1 (5.0 mol%), and 1,8-diazabicycloundec-7-ene(DBU) (2.0 mmol) in DMF (5 mL) was taken. The reaction mixture was stirred at 100C in air for 5 h. At the end of this time, the reaction mixture was diluted with EtOAc(20 mL) and washed with water (3 9 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and the solvent was stripped off under reduced pressure. The residue was subjected to column chromatography on silica gel using ethyl acetate and n-hexane mixture to afford the desired product. The products were characterized by 1H and 13C NMR analysis. |
78% | With anthracen-9-ylmethylene-(4-methoxyphenyl)amine; palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 100℃; for 2.5h; | General procedure: A mixture of arylboronic acid (1.0mmol), phenylacety-lene (1.2mmol), Pd(OAc) 2 (1.0mol%), L (1.0mol%) and 1,8-diazabicycloundec-7-ene (DBU) (2.0mmol) in DMF (5mL) was stirred at 100C in air for 4h. The reaction mixture was then diluted with EtOAc (20mL) and washed with water (3 × 10mL). The organic layer was dried over anhydrous Na 2 SO 4 , filtered and the solvent was removed. The residue was subjected to column chromatography on silica gel using ethyl acetate and n-hexane mixture to afford the desired product. The products were characterized by 1 H and 13 C NMR analysis. |
Yield | Reaction Conditions | Operation in experiment |
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80% | After 5.9 g (22 mmol) of PPh3 and 1.5 g (22 mmol) of zinc powder were dissolved in 22 ml of dichloromethane at 0C, 7.4 g (22 mmol) of CBr4 compound was added thereto in small fractions for 30 minutes while stirring. The mixture was further stirred for 1 hour at room temperature. The temperature was lowered to 0C, and then 577 mg (2.8 mmol) of Compound 1-18 was added thereto in small fractions for 30 minutes. After that, the result was stirred for one day at room temperature. After the reaction completed, the result was extracted with ethyl acetate and water. The organic layer was dried using anhydrous sodium sulfate and filtered, and after the solvent was removed by vacuum distillation again, the result was separated and purified using column chromatography, and 811 mg (80%) of target Compound 2-18 was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With toluene-4-sulfonic acid; In 1,2-dichloro-ethane; at 200℃; for 0.5h;Microwave irradiation; | General procedure: A solution of <strong>[59046-72-9]2-(phenylethynyl)benzaldehyde</strong> (1) (0.60 mmol, 124 mg), alkyne 2 (0.30 mmol), and TsOH.H2O(0.90 mmol, 171 mg) in ClCH2CH2Cl (2.0 mL) was treated at 200 Cfor 30 min under microwave condition (Biotage INITIATOR; Allreactions were carried out under temperature-constant operation). Thereaction mixture was diluted with CHCl3 and washed with saturatedNaHCO3 (aq) and brine. The organic layer was dried over MgSO4.After removal of the solvent under reduced pressure, the residue waspurified by chromatography on SiO2 to give the naphthalene derivatives. Further purification was carried out a recyclable preparativeHPLC, if necessary. The structures of the products were assigned bytheir NMR spectra. The product was characterized by comparing itsspectral data with previous report.8a |
Yield | Reaction Conditions | Operation in experiment |
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50% | General procedure: A solution of 2-alkynylbenzaldehyde 1 (0.3 mmol), sulfonohydrazide (0.3 mmol, 1.0 equiv) in DCM (1.0 mL) was stirred at room temperature for 10 minutes in a tube. Then Br2 or I2 (0.33 mmol, 1.1 equiv) were added. The reaction mixture was stirred at room temperature for 10 minutes with Br2 or 24 hours with I2. After workup with Na2S2O3, ketone or aldehyde 3 (0.6 mmol, 2.0 equiv) and K3PO4 (0.9 mmol, 3.0 equiv) were added to the solution. The reaction mixture was stirred at 70 C vigorously until completion of the reaction. Then the mixture was diluted with ethyl acetate (5.0 mL), and quenched with water (5.0 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting with PE/EA = 50/1 to 20/1) to provide the desired product 3. column chromatography on silica gel (eluting with PE/EA = 50/1 to 20/1) to provide the desired product 3. 1.0 equiv) in DCM (1.0 mL) was stirred at room temperature for 10 minutes in a tube. Then Br2 or I2 (0.33 mmol, 1.1 equiv) were added. The reaction mixture was stirred at room temperature for 10 minutes with Br2 or 24 hours with I2. After workup with Na2S2O3, ketone or aldehyde 3 (0.6 mmol, 2.0 equiv) and K3PO4 (0.9 mmol, 3.0 equiv) were added to the solution. The reaction mixture was stirred at 70 C vigorously until completion of the reaction. Then the mixture was diluted with ethyl acetate (5.0 mL), and quenched with water (5.0 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting with PE/EA = 50/1 to 20/1) to provide the desired product 3. column chromatography on silica gel (eluting with PE/EA = 50/1 to 20/1) to provide the desired product 3. |
A182351 [189008-33-1]
2-(p-Tolylethynyl)benzaldehyde
Similarity: 1.00
A182351 [189008-33-1]
2-(p-Tolylethynyl)benzaldehyde
Similarity: 1.00
A182351 [189008-33-1]
2-(p-Tolylethynyl)benzaldehyde
Similarity: 1.00