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[ CAS No. 59046-72-9 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 59046-72-9
Chemical Structure| 59046-72-9
Chemical Structure| 59046-72-9
Structure of 59046-72-9 * Storage: {[proInfo.prStorage]}
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Product Details of [ 59046-72-9 ]

CAS No. :59046-72-9 MDL No. :MFCD09030317
Formula : C15H10O Boiling Point : -
Linear Structure Formula :- InChI Key :SDSQNHMKRHPAIM-UHFFFAOYSA-N
M.W :206.24 Pubchem ID :10013210
Synonyms :

Calculated chemistry of [ 59046-72-9 ]

Physicochemical Properties

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 : 17.07 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.14 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.63
Log Po/w (XLOGP3) : 3.4
Log Po/w (WLOGP) : 2.98
Log Po/w (MLOGP) : 3.44
Log Po/w (SILICOS-IT) : 4.09
Consensus Log Po/w : 3.31

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.75
Solubility : 0.0367 mg/ml ; 0.000178 mol/l
Class : Soluble
Log S (Ali) : -3.44
Solubility : 0.0753 mg/ml ; 0.000365 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.95
Solubility : 0.00231 mg/ml ; 0.0000112 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.4

Safety of [ 59046-72-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 59046-72-9 ]

* 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.

  • Downstream synthetic route of [ 59046-72-9 ]

[ 59046-72-9 ] Synthesis Path-Downstream   1~80

  • 1
  • [ 623-73-4 ]
  • [ 59046-72-9 ]
  • [ 145838-87-5 ]
YieldReaction ConditionsOperation in experiment
82% With niobium pentachloride In dichloromethane at 25℃; for 16h;
71% With niobium pentachloride In dichloromethane at 25℃; 15 General procedure for the niobium-catalyzed formation of the ortho-alkynyl-β-keto esters (3a-t) 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.
57% With tin(ll) chloride In dichloromethane for 4h; Ambient temperature;
With niobium pentachloride In dichloromethane at 25℃; for 16h;

  • 2
  • [ 536-74-3 ]
  • [ 6630-33-7 ]
  • [ 59046-72-9 ]
YieldReaction ConditionsOperation in experiment
99% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 2h;
99% Stage #1: ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: ethynylbenzene With copper (I) iodide In tetrahydrofuran at 20℃; for 24h;
99% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 34h; Inert atmosphere;
98% With copper (I) iodide In tetrahydrofuran for 3h; Heating;
98% With copper (I) iodide; trans-bis(triphenylphosphine)palladium(II) dichloride In triethylamine at 60℃; for 4h; Inert atmosphere; 1 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 60°C 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; 2.1 General procedures for the synthesis of substrates 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).
97% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine In tetrahydrofuran at 30 - 40℃; for 2h; Schlenk technique;
96% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran Inert atmosphere; Schlenk technique;
96% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 8h; Inert atmosphere;
95% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 70℃; Inert atmosphere;
95% With copper (I) iodide; bis(benzonitrile)palladium(II) chloride; tri-tert-butyl phosphine; triethylamine In toluene at 20℃; for 8h; Inert atmosphere; 4 Sonogashira Cross Coupling of 2-bromobenzaldeyde with Phenylacetylene (B1) 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; 4.2. Typical procedure for preparation of N-(o-arylethynyl)benzylp-toluenesuldonamide 1 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.
94% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine
94% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In triethylamine at 50℃;
94% With tripotassium phosphate tribasic; ϖ-allylpalladium (II) chloride dimer; N1,N1,N2,N2-tetrakis[(diphenylphosphino)methyl]ethane-1,2-diamine In 1,4-dioxane at 105℃; for 20h; Inert atmosphere;
94% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; Inert atmosphere;
94% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 6h; Schlenk technique; Inert atmosphere;
94% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; Schlenk technique; Inert atmosphere;
94% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; Inert atmosphere; Sealed tube;
94% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; Inert atmosphere;
93% With copper (I) iodide; triphenylphosphine In triethylamine for 6h; Heating;
93% With triethylamine In tetrahydrofuran for 3h; Heating;
93% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N,N-diisopropylamine In toluene at 80℃; for 20h; Inert atmosphere;
93% Stage #1: ethynylbenzene; ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine for 0.0833333h; Inert atmosphere; Stage #2: With copper (I) iodide at 50℃; for 4h; Inert atmosphere;
93% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran Inert atmosphere; Schlenk technique; Reflux;
93% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique;
92% With triethylamine at 80℃; for 18h;
92% With copper (I) iodide; triethylamine at 28℃; for 12h;
92% With copper (I) iodide; bis(benzonitrile)palladium(II) chloride; tri-tert-butyl phosphine; triethylamine In toluene Inert atmosphere;
92% Stage #1: ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran Inert atmosphere; Schlenk technique; Stage #2: ethynylbenzene In tetrahydrofuran for 3h; Schlenk technique; Inert atmosphere; Reflux;
92% With piperidine; 1,3-bis(5-ferrocenylisoxazoline-3-yl)benzene; tetrabutylammonium bromide; palladium diacetate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 60℃; for 3h;
92% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; 1,1'-bis(diphenylphosphino)ferrocene; N-ethyl-N,N-diisopropylamine In tetrahydrofuran Reflux; Inert atmosphere; 2-Phenylethynylbenzaldehyde (7g) 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).
92% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 60℃; for 4h; Inert atmosphere;
92% Stage #1: ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: ethynylbenzene With copper (I) iodide In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;
91% With copper (I) iodide; triethylamine at 50℃; for 4h;
91% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 4h;
91% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 4h;
91% With copper (I) iodide; triethylamine at 80℃; for 16h;
91% With triethylamine at 50℃; for 5h; 2.b 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 50°C 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
91% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 1h; Inert atmosphere;
91% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In triethylamine at 65℃; for 16h;
91% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine In tetrahydrofuran at 70℃; Inert atmosphere;
91% Stage #1: ethynylbenzene; ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 20℃; for 0.25h; Inert atmosphere; Stage #2: With copper (I) iodide at 50℃; for 1h; Inert atmosphere;
91% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 60℃; for 2h; Inert atmosphere;
90% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; potassium carbonate for 17h; Neat (no solvent);
90% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran Inert atmosphere; Reflux;
90% With triethylamine In lithium hydroxide monohydrate at 90 - 100℃; for 4h;
90% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 60℃; for 19h; Inert atmosphere;
90% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; Schlenk technique; Inert atmosphere;
90% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 60℃; for 4h; 1.1 (1) Preparation of Compound 3-1 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 [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 1h;
89% With potassium carbonate In ethanol; lithium hydroxide monohydrate at 100℃; for 2h;
89% Stage #1: ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 0.25h; Inert atmosphere; Stage #2: ethynylbenzene at 20℃; for 12h; Inert atmosphere;
89% With C19H16ClNPdS; potassium carbonate In N,N-dimethyl-formamide at 90℃; for 5h;
89% With tripotassium phosphate tribasic; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 120℃; Schlenk technique; Inert atmosphere; Alkynes 2 and 9; General Procedure 1 (GP 1) 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; General procedure for the synthesis of aromatic alkynols 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.
88% With copper (I) iodide; triphenylphosphine In triethylamine at 80℃; for 10h;
88% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N,N-diisopropylamine In toluene at 20 - 50℃; Inert atmosphere; Sealed tube;
88% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 0 - 45℃; Inert atmosphere;
87% With piperidine In neat (no solvent) at 90℃; for 5h; Green chemistry; 2.4. General procedure for Sonogashira cross coupling reactions 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).
86% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N,N-diisopropylamine In tetrahydrofuran at 20℃; Inert atmosphere;
86% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20 - 50℃; Inert atmosphere;
85% With copper (I) iodide; triethylamine; triphenylphosphine at 80℃; for 5h;
85% With copper (I) iodide; trans-bis(triphenylphosphine)palladium(II) dichloride; triethylamine at 50℃; for 4h; Inert atmosphere;
85% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 80℃; Inert atmosphere;
85% With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 90℃; for 6h;
85% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 10h; Inert atmosphere; 12.1 Example 12Preparation of Compound 12 (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).
85% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique;
84% With copper (I) iodide; palladium diacetate; triethylamine; triphenylphosphine at 80℃; for 5h;
84% Stage #1: ortho-bromobenzaldehyde With copper (I) iodide; triethylamine at 23℃; for 0.25h; Inert atmosphere; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) for 0.25h; Inert atmosphere; Stage #3: ethynylbenzene at 20℃; for 12h; Inert atmosphere;
84% Stage #1: ortho-bromobenzaldehyde With copper (I) iodide; triethylamine at 23℃; for 0.25h; Inert atmosphere; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) for 0.25h; Inert atmosphere; Stage #3: ethynylbenzene at 20℃; for 12h; Inert atmosphere;
84% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 12h; Inert atmosphere; a a) Synthesis of 2-(phenylethynyl)benzaldehyde (S-1) 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%).
84% Stage #1: ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 0.166667h; Inert atmosphere; Schlenk technique; Reflux; Stage #2: ethynylbenzene Inert atmosphere; Schlenk technique; Reflux;
83% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N,N-diisopropylamine In tetrahydrofuran at 80℃; for 3h; Inert atmosphere;
83% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine In tetrahydrofuran at 0 - 45℃; Inert atmosphere; Schlenk technique;
82% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In N,N-dimethyl-formamide at 40 - 50℃; for 1h;
82% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In N,N-dimethyl-formamide
82% With triethylamine In N,N-dimethyl-formamide at 80℃; for 20h;
82% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 55℃; for 24h; Inert atmosphere;
82% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In triethylamine at 50℃; for 3h; 4 Preparation of Compound 1-18 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 50°C. 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.
81% With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 50℃; for 12h; Inert atmosphere;
80% With copper (I) iodide; triethylamine; triphenylphosphine for 48h; Heating;
80% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; triphenylphosphine for 48h; Heating;
80% With potassium carbonate at 100℃; for 1h; Schlenk technique;
80% Stage #1: ethynylbenzene; ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 20℃; for 0.333333h; Inert atmosphere; Schlenk technique; Stage #2: With copper (I) iodide at 50℃; for 12h; Inert atmosphere; Schlenk technique;
80% Stage #1: ethynylbenzene; ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 20℃; for 0.333333h; Inert atmosphere; Stage #2: With copper (I) iodide at 50℃; for 12h; Inert atmosphere;
79% With copper (I) iodide; palladium diacetate; triethylamine; triphenylphosphine
79% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; Inert atmosphere;
79% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 80℃; for 18h; Sealed tube; Inert atmosphere; regioselective reaction;
79% With copper (I) iodide; C26H24N6NiS4; triethylamine In N,N-dimethyl-formamide at 80℃; for 8h; Inert atmosphere; Typical procedure for the Sonogashira reaction of aryl bromides with phenylacetylene 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; Synthesis of alkyne 2[5] 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 potassium carbonate; cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane In N,N-dimethyl-formamide at 140℃; for 20h;
78% With C37H29ClN3PPdS; triethylamine In N,N-dimethyl-formamide at 20℃; for 12h; Typical procedure for the Sonogashira cross-coupling reaction 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.
78% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 60℃; Inert atmosphere;
77% Stage #1: ethynylbenzene; ortho-bromobenzaldehyde With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: With copper (I) iodide at 50℃; for 5.5h; Inert atmosphere;
77% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; Inert atmosphere;
76% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; Inert atmosphere;
76% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 50℃; Inert atmosphere;
76% With copper (I) iodide; palladium diacetate; triethylamine; dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane In neat liquid at 20℃; Schlenk technique; Inert atmosphere;
75% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper(II) iodide; triethylamine In tetrahydrofuran at 20℃; for 15h; Inert atmosphere;

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[98]Ye, Fei; Haddad, Mansour; Michelet, Véronique; Ratovelomanana-Vidal, Virginie [Organic Letters, 2016, vol. 18, # 21, p. 5612 - 5615]
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  • 3
  • [ 59046-72-9 ]
  • [ 1576-35-8 ]
  • [ 75586-32-2 ]
YieldReaction ConditionsOperation in experiment
89% With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In nonane; dimethyl sulfoxide; acetonitrile at 70℃; for 2.5h; Molecular sieve;
87% In methanol at 20℃; for 2h;
77% With hydrogenchloride In ethanol Ambient temperature; dark;
62% In methanol at 20℃; for 2h;
53% In ethanol at 20℃; for 1h; 1.2 (2) Preparation of Compound 3-2 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 1,2-dichloro-ethane at 20℃; for 1h; Inert atmosphere;
In 1,2-dichloro-ethane at 20℃; for 0.166667h;
In acetonitrile at 80℃; for 0.25h;
In methanol at 60℃; Inert atmosphere;
In dichloromethane at 20℃; for 0.5h; 4.2. General experimental procedure for the multi-component reaction of 2-alkynylbenzaldehyde, 4-methylbenzenesulfono-hydrazide, carbodiimide, and bromine 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℃; 1.2 (2) intermediate compound 4a-4i synthesis: (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℃; 2 (2) intermediate compound 4a-4i synthesis: 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.
In methanol at 20℃;

Reference: [1]Hao, Wen-Juan; Du, Yan; Wang, Dan; Jiang, Bo; Gao, Qian; Tu, Shu-Jiang; Li, Guigen [Organic Letters, 2016, vol. 18, # 8, p. 1884 - 1887]
[2]Cai, Zhong-Jian; Ji, Shun-Jun; Li, Fang-Hui; Wang, Dian-Liang; Wu, Bing; Yao, Hai-Feng [Organic and Biomolecular Chemistry, 2020, vol. 18, # 38, p. 7577 - 7584]
[3]Anderson, Patrick N.; Sharp, John T. [Journal of the Chemical Society. Perkin transactions I, 1980, p. 1331 - 1334]
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[5]Current Patent Assignee: LT SAMBO CO LTD - US2020/308150, 2020, A1 Location in patent: Paragraph 0136; 0138; 0143
[6]Chen, Zhiyuan; Wu, Jie [Organic Letters, 2010, vol. 12, # 21, p. 4856 - 4859]
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[11]Current Patent Assignee: HUNAN UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN105330663, 2016, A Location in patent: Paragraph 0038; 0041; 0042
[12]Current Patent Assignee: HUNAN UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN105294689, 2016, A Location in patent: Paragraph 0038; 0039
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  • 4
  • [ 59046-72-9 ]
  • [ 1066-54-2 ]
  • [ 879286-37-0 ]
YieldReaction ConditionsOperation in experiment
100% With n-butyllithium In tetrahydrofuran at -78℃;
88% Stage #1: trimethylsilylacetylene With ethylmagnesium bromide In tetrahydrofuran at 20℃; for 4h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at 20℃; for 4h;
85% With SDDA In benzene
64% With ethyl bromide; magnesium In tetrahydrofuran at 0 - 20℃; Inert atmosphere;
49% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -78℃; Inert atmosphere;
49% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; a a) Synthesis of 1-(2-(phenylethynyl)phenyl)-3-(trimethylsilyl)prop-2-yn-1-ol (S-5) 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. 2-(phenylethynyl)benzaldehyde (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%).
Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: o-(phenylethynyl)benzaldehyde for 0.25h;
Stage #1: trimethylsilylacetylene With ethylmagnesium bromide In tetrahydrofuran at 0 - 20℃; for 0.25h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere;

  • 5
  • [ 59046-72-9 ]
  • [ 4301-14-8 ]
  • [ 183312-49-4 ]
YieldReaction ConditionsOperation in experiment
99% In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Schlenk technique;
99% In tetrahydrofuran at 0 - 20℃;
98% In tetrahydrofuran at 0 - 20℃; for 2h; 1 2-Phenynylbenzaldehyde (10.094g 49mmol) and 50ml of anhydrous tetrahydrofuran were added to a 500ml round-bottomed flask and stirred at 0°C. 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%)
97% In tetrahydrofuran at 20℃; for 16h;
91% In tetrahydrofuran at 0 - 20℃; Inert atmosphere;
86% Stage #1: o-(phenylethynyl)benzaldehyde; acetylenemagnesium bromide In tetrahydrofuran; hexane at 0℃; Schlenk technique; Inert atmosphere; Stage #2: With ammonium chloride In tetrahydrofuran; hexane; water at 0℃;
In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;
In tetrahydrofuran at 0 - 20℃; for 4h; Inert atmosphere;

  • 6
  • [ 59046-72-9 ]
  • [ 536-74-3 ]
  • [ 216306-60-4 ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: phenylacetylene With ethylmagnesium bromide In tetrahydrofuran at 40℃; for 0.5h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at 23 - 25℃; Stage #3: With water; ammonium chloride In tetrahydrofuran
93% Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.75h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at -78 - 20℃; Inert atmosphere;
87% Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at -78 - 20℃; for 4h; Inert atmosphere;
87% Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at 20℃; for 2h; Inert atmosphere;
86% Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.333333h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at -78 - 28℃; Further stages.;
86% Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;
76% Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; Schlenk technique;
With sodium aluminum diethyl dihydride 1.) C6H6, 3 h, 2.) C6H6, 0 deg C, 1 h; Yield given. Multistep reaction;
Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -78 - 20℃; for 12h;
Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -78 - 20℃; for 1h;
Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere;
Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique;
Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -78 - 20℃;
Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.75h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at 25℃; for 2h;

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[2]Harris, Trevor; Gomes, Gabriel Dos Passos; Clark, Ronald J.; Alabugin, Igor V. [Journal of Organic Chemistry, 2016, vol. 81, # 14, p. 6007 - 6017]
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[6]Sun, Ning; Xie, Xin; Wang, Gaonan; Chen, Haoyi; Liu, Yuanhong [Advanced Synthesis and Catalysis, 2017, vol. 359, # 8, p. 1394 - 1401]
[7]Chen, Zhiyuan; Jia, Xuegong; Huang, Jiapian; Yuan, Jianjun [Journal of Organic Chemistry, 2014, vol. 79, # 21, p. 10674 - 10681]
[8]Schmittel, Michael; Strittmatter, Marc; Schenk, Wolfdieter A.; Hagel, Michael [Zeitschrift fur Naturforschung, B: Chemical Sciences, 1998, vol. 53, # 9, p. 1015 - 1020]
[9]Patil, Nitin T.; Pahadi, Nirmal K.; Yamamoto, Yoshinori [Journal of Organic Chemistry, 2005, vol. 70, # 24, p. 10096 - 10098]
[10]Ponpandian, Thanasekaran; Muthusubramanian, Shanmugam; Rajagopal, Sridharan [European Journal of Organic Chemistry, 2013, # 19, p. 3974 - 3977]
[11]Pati, Kamalkishore; Hughes, Audrey M.; Phan, Hoa; Alabugin, Igor V. [Chemistry - A European Journal, 2014, vol. 20, # 2, p. 390 - 393]
[12]Xu, Murong; Zheng, Zhong; Wang, Mengdan; Kong, Lingkai; Ao, Yujuan; Li, Yanzhong [Organic and Biomolecular Chemistry, 2018, vol. 16, # 45, p. 8761 - 8768]
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  • 7
  • [ 59046-72-9 ]
  • [ 13141-40-7 ]
YieldReaction ConditionsOperation in experiment
100% With sodium tetrahydroborate In methanol at 0℃; for 0.5h; 2-Phenoxybenzylalcohol (3d) 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.
97% With sodium tetrahydroborate In methanol at 0℃; for 16h; Inert atmosphere;
95% With sodium tetrahydroborate In methanol
95% With sodium tetrahydroborate In methanol at 0℃; for 0.333333h; General procedure for the synthesis of aromatic alkynols 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.
88% With sodium tetrahydroborate In methanol at 0 - 20℃; General procedure for the synthesis of 2-arylalkynyl methanols 8/9. 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.
88% With sodium tetrahydroborate In methanol at 0℃; for 0.5h; Inert atmosphere; Schlenk technique;
85% With sodium tetrahydroborate In methanol at 0℃; for 0.5h; Schlenk technique;
82% With sodium tetrahydroborate In ethanol at 20℃; for 2h;
With sodium tetrahydroborate
With sodium tetrahydroborate
1.80 g With sodium tetrahydroborate In methanol at 0℃;
With diisobutylaluminium hydride In dichloromethane at -78 - 20℃;

Reference: [1]Fukuda, Miwa; Sasaki, Tomomi; Hashimoto, Tomoko; Miyachi, Hiroyuki; Waki, Minoru; Asai, Akira; Takikawa, Osamu; Ohno, Osamu; Matsuno, Kenji [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 17, p. 2846 - 2849]
[2]Ackermann, Martin; Bucher, Janina; Rappold, Melissa; Graf, Katharina; Rominger, Frank; Hashmi, A. Stephen K. [Chemistry - An Asian Journal, 2013, vol. 8, # 8, p. 1786 - 1794]
[3]Hamze, Abdallah; Provot, Olivier; Alami, Mouad; Brion, Jean-Daniel [Organic Letters, 2005, vol. 7, # 25, p. 5625 - 5628]
[4]Yu, Shu-Yan; Gao, Li-Hong; Wu, Jing-Xin; Lan, Hong-Bing; Ma, Yi; Yin, Zhi-Gang [Chemical Papers, 2020, vol. 74, # 10, p. 3303 - 3310]
[5]Asthana, Mrityunjaya; Singh, Jay Bahadur; Singh, Radhey M. [Tetrahedron Letters, 2016, vol. 57, # 5, p. 615 - 618]
[6]Hu, Yue; Huang, Hanmin [Organic Letters, 2017, vol. 19, # 19, p. 5070 - 5073]
[7]Long, Peng-Wei; Bai, Xing-Feng; Ye, Fei; Li, Li; Xu, Zheng; Yang, Ke-Fang; Cui, Yu-Ming; Zheng, Zhan-Jiang; Xu, Li-Wen [Advanced Synthesis and Catalysis, 2018, vol. 360, # 15, p. 2825 - 2830]
[8]Jongcharoenkamol, Jira; Chuathong, Patsapon; Amako, Yuka; Kono, Masato; Poonswat, Kasam; Ruchirawat, Somsak; Ploypradith, Poonsakdi [Journal of Organic Chemistry, 2018, vol. 83, # 21, p. 13184 - 13210]
[9]Orita, Akihiro; Yoshioka, Naonori; Struwe, Petra; Braier, Arnold; Beckmann, Anke; Otera, Junzo [Chemistry - A European Journal, 1999, vol. 5, # 4, p. 1355 - 1363]
[10]Mukhopadhyaya, Jayanta Kumar; Kozikowski, Alan P.; Grajkowska, Ewa; Pshenichkin, Sergey; Wroblewski, Jarda T. [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 14, p. 1919 - 1924]
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[12]Fischer, Dirk; Tomeba, Hisamitsu; Pahadi, Nirmal K.; Patil, Nitin T.; Huo, Zhibao; Yamamoto, Yoshinori [Journal of the American Chemical Society, 2008, vol. 130, # 46, p. 15720 - 15725]
  • 8
  • [ 59046-72-9 ]
  • [ 37993-76-3 ]
YieldReaction ConditionsOperation in experiment
98% With silver hexafluoroantimonate; 4-methoxypyridine N-oxide; sodium tetrachloroaurate(III) dihyrate; ammonium acetate In acetonitrile at 85℃; for 2h; Sealed tube; Inert atmosphere; regioselective reaction;
95% With ammonium acetate; silver nitrate In <i>tert</i>-butyl alcohol at 27 - 30℃; for 2h; Inert atmosphere;
86% With ammonium bicarbonate; silver nitrate In acetonitrile at 120℃; for 12h;
78% With 4-aminomethylphenol; silver nitrate In ethanol at 80℃; 1; 2; 3; 4 Example 4 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; Typical procedure: 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; Typical procedure for 3 General procedure: To a solution of 2-(phenylethynyl)benzaldehyde 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.
58% With ammonia In methanol at 130℃; for 0.5h; Microwave irradiation;
57% With ammonium bicarbonate; silver nitrate In acetonitrile at 100℃; 1.2 (2) Synthesis of the target compound 4a-4l: 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 120°C 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.
45% With ammonia In ethanol at 80℃; for 2h;
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: 51 percent / potassium carbonate; Pd(PPh3)4; ethyl 4-bromo-2-butenoate / dimethylsulfoxide / 24 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: 14 percent / potassium carbonate; Pd(PPh3)4 / dimethylformamide / 24 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: 45 percent / potassium carbonate; Pd(PPh3)4 / dimethylsulfoxide / 24 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: 16 percent / potassium carbonate; Pd(PPh3)4 / dimethylformamide / 24 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: 13 percent / potassium carbonate; Pd(PPh3)4 / dimethylformamide / 120 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: 18 percent / potassium carbonate; Pd(PPh3)4 / dimethylformamide / 48 h / 100 °C
Multi-step reaction with 2 steps 1: 98 percent / 24 h / 20 °C 2: 100 percent / CuI / dimethylformamide / 3 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 2 h / 25 °C 2: 100 percent / CuI / dimethylformamide / 3 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: 48 percent / Pd(PPh3)4; K2CO3; o-EtO2CC6H4I / dimethylformamide / 11 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: 14 percent / K2CO3 / Pd(PPh3)4 / dimethylformamide / 24 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: K2CO3 / Pd(PPh3)4 / dimethylformamide / 11 h / 100 °C
Multi-step reaction with 2 steps 1: 97 percent / H2O / 12 h / 20 °C 2: K2CO3 / Pd(PPh3)4 / dimethylformamide / 7 h / 100 °C
Multi-step reaction with 2 steps 1: 99 percent Spectr. / CDCl3 / 1 h / 20 °C 2: 74 percent / NH3 / CH2Cl2 / 20 h
Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride / acetonitrile / 10 - 12 h / 20 °C 2: zinc(II) chloride / 1,4-dioxane / 12 h / 110 °C 3: dichloro bis(acetonitrile) palladium(II); tributyl-amine; tetrabutylammonium acetate; zinc(II) oxide / toluene / 22 h / 120 °C
Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride; pyridine / ethanol / 2 h / Reflux; Inert atmosphere 2: silver trifluoromethanesulfonate / dichloromethane / 0.5 h / 20 °C / Inert atmosphere 3: silver trifluoromethanesulfonate; copper(II) bis(trifluoromethanesulfonate) / N,N-dimethyl-formamide; 1,2-dichloro-ethane / 24 h / 120 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: 24 h / 20 °C / Inert atmosphere 2: silver(I) exchanged K10-montmorillonite clay / N,N-dimethyl-formamide / 6 h / 100 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: 24 h / 20 °C / Inert atmosphere 2: AgI–K10 montmorillonite clay / N,N-dimethyl-formamide / 6 h / 100 °C / Inert atmosphere; Green chemistry
Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride / acetonitrile / 20 °C 2: zinc(II) chloride / 1,4-dioxane / 12 h / 110 °C 3: ytterbium(III) oxide; tetrabutylammonium acetate / toluene / 24 h / 120 °C
Multi-step reaction with 3 steps 1: acetonitrile / 5 h / 80 °C 2: silver trifluoromethanesulfonate / acetonitrile / 3 h / 80 °C 3: 1,3-bis(mesityl)imidazolium chloride; dirhodium tetraacetate; caesium carbonate; water / toluene / 24 h / 95 °C / Schlenk technique
Multi-step reaction with 2 steps 1: hydrazine hydrochloride / ethanol / 3 h / 20 °C 2: silver nitrate / dimethyl sulfoxide / 0.5 h / 100 °C
With copper(l) iodide; ammonium acetate In tetrahydrofuran; water at 50℃; for 2h; Green chemistry; General Procedure for the synthesis of Isoquinolines/Furopyridines/Thienopyridines 4(a-r): Synthesis of 3-phenylisoquinoline (4a): 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.
Multi-step reaction with 2 steps 1: 24 h / 20 °C / Inert atmosphere 2: copper(l) iodide / N,N-dimethyl-formamide / 12 h / 100 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: dichloromethane / 20 °C / Molecular sieve 2: sodium hydroxide; tetrakis(triphenylphosphine) palladium(0); water / N,N-dimethyl-formamide / 4 h / 135 °C
Multi-step reaction with 2 steps 1: dichloromethane / 20 °C / Molecular sieve 2: caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0); water / N,N-dimethyl-formamide / 4 h / 135 °C
Multi-step reaction with 4 steps 1.1: zinc; hydroxylamine hydrochloride / ethanol / Inert atmosphere 1.2: 12 h / 0 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; iodine / acetonitrile / 12 h / 20 - 60 °C / Inert atmosphere 3.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 10 h / 20 °C / Inert atmosphere 4.1: zinc / ethanol / 12 h / Inert atmosphere; Reflux
Multi-step reaction with 2 steps 1: acetic acid / tetrahydrofuran / 6 h / 20 °C 2: silver hexafluoroantimonate / 1,2-dichloro-ethane; 2,2,2-trifluoroethanol / 6 h / 80 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 2 steps 1.1: hydroxylamine hydrochloride; sodium acetate / acetonitrile / 12 h / 20 °C 2.1: silver trifluoromethanesulfonate / 1,2-dichloro-ethane / 1 h / 60 °C / Inert atmosphere 2.2: 20 °C / Inert atmosphere

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  • 9
  • [ 59046-72-9 ]
  • [ 75-64-9 ]
  • [ 241813-23-0 ]
YieldReaction ConditionsOperation in experiment
100% at 20℃; for 24h;
100% at 20℃; for 12h; 12.2 (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).
at 20℃; Molecular sieve;
at 20℃; for 24h; Inert atmosphere;
at 20℃; for 24h; Inert atmosphere;
In dichloromethane at 20℃; Molecular sieve;
In dichloromethane at 20℃; Molecular sieve;

  • 10
  • [ 67-56-1 ]
  • [ 59046-72-9 ]
  • [ 60815-13-6 ]
YieldReaction ConditionsOperation in experiment
96% at 25℃;
93% In N,N-dimethyl-formamide at 70℃;
92% With C58H44Ag2F6O6S6 In dichloromethane at 20℃; for 12h; Inert atmosphere; Schlenk technique; General procedure for intramolecular cyclization of alkyne 2 to compound 4 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.
90% With p-benzoquinone In 1,4-dioxane at 10℃; for 0.5h;
84% With palladium diacetate In tetrahydrofuran at 25℃; for 0.5h; Schlenk technique; Inert atmosphere; regioselective reaction;
74% With dimethylsulfide gold(I) chloride In methanol; dichloromethane at 20℃; for 0.5h;

  • 11
  • [ 64-17-5 ]
  • [ 59046-72-9 ]
  • [ 127233-59-4 ]
YieldReaction ConditionsOperation in experiment
76% With p-benzoquinone In 1,4-dioxane at 10℃; for 0.5h;
  • 12
  • [ 1455-13-6 ]
  • [ 59046-72-9 ]
  • 1-methoxy-3-phenyl-4-deuterium-1H-isochromene [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With p-benzoquinone In 1,4-dioxane at 10℃; for 0.5h;
  • 14
  • [ 59046-72-9 ]
  • [ 75-64-9 ]
  • (E)-tert-butyl([2-(2-phenylethynyl)phenyl]methylidene})amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% at 20℃; for 24h;
97% With water at 25℃; for 2h;
97% In water at 20℃; for 12h;
97% With magnesium sulfate In dichloromethane at 40℃; for 5h;
94% at 20℃; for 24h;
94% at 20℃; for 24h; Inert atmosphere;
With triethylamine at 20℃; for 24h; 2.b 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 50°C 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

  • 15
  • [ 241813-23-0 ]
  • [ 59046-72-9 ]
  • [ 37993-76-3 ]
  • 16
  • [ 673-32-5 ]
  • [ 59046-72-9 ]
  • [ 83179-46-8 ]
YieldReaction ConditionsOperation in experiment
86% With Difluoroacetic acid In 1,2-dichloro-ethane at 100℃; for 0.25h;
86% With zinc(II) chloride In 1,2-dichloro-ethane at 80℃; for 36h; Inert atmosphere; regiospecific reaction;
63% With toluene-4-sulfonic acid In 1,2-dichloro-ethane at 200℃; for 0.5h; Microwave irradiation; General procedure for the reaction of 2-(phenylethynyl)benzaldehyde (1) and alkynes 2 General procedure: A solution of 2-(phenylethynyl)benzaldehyde (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
  • 17
  • [ 67-56-1 ]
  • [ 59046-72-9 ]
  • [ 587882-43-7 ]
YieldReaction ConditionsOperation in experiment
93% With iodine; potassium carbonate In dichloromethane at 20℃;
84% Stage #1: o-(phenylethynyl)benzaldehyde With tetrafluoroboric acid; [bis(pyridine)iodine]+ tetrafluoroborate In diethyl ether; dichloromethane at 0 - 20℃; for 0.5h; Stage #2: methanol In diethyl ether; dichloromethane for 1h;
84% Stage #1: o-(phenylethynyl)benzaldehyde With tetrafluoroboric acid; Barluenga reagent In diethyl ether; dichloromethane at 20℃; for 0.5h; Stage #2: methanol In diethyl ether; dichloromethane at 20℃; for 1h; Further stages.;
  • 18
  • [ 1942-45-6 ]
  • [ 59046-72-9 ]
  • 2,3-dipropylnaphthalene [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With Difluoroacetic acid In 1,2-dichloro-ethane at 100℃; for 0.25h;
51% With zinc(II) chloride In 1,2-dichloro-ethane at 80℃; for 20h; Inert atmosphere; regiospecific reaction;
  • 19
  • [ 59046-72-9 ]
  • [ 536-74-3 ]
  • [ 612-94-2 ]
YieldReaction ConditionsOperation in experiment
90% With Difluoroacetic acid In 1,2-dichloro-ethane at 100℃; for 0.25h;
81% With zinc(II) chloride In 1,2-dichloro-ethane at 80℃; for 12h; Inert atmosphere; regiospecific reaction;
50% With silver trifluoromethanesulfonate; aniline In dichloroethane at 80℃; for 6h;
36% With trifluorormethanesulfonic acid In dichloromethane at 20℃; for 24h;
28% With toluene-4-sulfonic acid In 1,2-dichloro-ethane at 200℃; for 0.5h; Microwave irradiation; General procedure for the reaction of 2-(phenylethynyl)benzaldehyde (1) and alkynes 2 General procedure: A solution of 2-(phenylethynyl)benzaldehyde (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

  • 20
  • [ 59046-72-9 ]
  • [ 932-87-6 ]
  • 2-bromo-3-phenylnaphthalene [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With Difluoroacetic acid; copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane at 100℃; for 0.25h; Inert atmosphere; 2 Step 2: Synthesis of Intermediate B13 (2-bromo-3-phenylnapthalene) Referring to Journal of the American Chemical Society, 2003, 125(36), 10921, a mixture of o-(phenylethynyl)benzaldehyde (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; step 2 Step 2: Synthesis of intermediate B13 (2-bromo-3-phenylnaphthalene) Referring Journal of the American Chemical Society, 2003, 125(36), 10921, To a mixture of o-(phenylethynyl)benzaldehyde (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%.
73% With Difluoroacetic acid In 1,2-dichloro-ethane at 100℃; for 0.25h;
  • 21
  • [ 59046-72-9 ]
  • [ 501-65-5 ]
  • [ 70489-30-4 ]
YieldReaction ConditionsOperation in experiment
96% With copper(II) bis(trifluoromethanesulfonate); trifluoroacetic acid In 1,2-dichloro-ethane at 100℃;
85% With Difluoroacetic acid In 1,2-dichloro-ethane at 100℃; for 0.25h;
54% With zinc(II) chloride In 1,2-dichloro-ethane at 80℃; for 20h; Inert atmosphere; regiospecific reaction;
49% With toluene-4-sulfonic acid In 1,2-dichloro-ethane at 200℃; for 0.5h; Microwave irradiation; General procedure for the reaction of 2-(phenylethynyl)benzaldehyde (1) and alkynes 2 General procedure: A solution of 2-(phenylethynyl)benzaldehyde (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

  • 22
  • [ 100-42-5 ]
  • [ 59046-72-9 ]
  • phenyl-(2-phenyl-naphthalen-1-yl)-methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With oxone||potassium monopersulfate triple salt; tetra-(n-butyl)ammonium iodide at 50℃; for 3h;
78% Stage #1: o-(phenylethynyl)benzaldehyde With tetrafluoroboric acid; Barluenga reagent In diethyl ether; dichloromethane at 20℃; for 0.5h; Stage #2: styrene In diethyl ether; dichloromethane at 20℃; for 1h;
78% Stage #1: o-(phenylethynyl)benzaldehyde With tetrafluoroboric acid; Barluenga reagent In diethyl ether; dichloromethane at 20℃; for 0.5h; Stage #2: styrene In diethyl ether; dichloromethane at 20℃; for 1h; Further stages.;
77% With iodine; potassium carbonate In dichloromethane for 0.5h;
76% With p-benzoquinone; zinc(II) iodide In ethyl acetate; toluene at 120℃; for 20h; Inert atmosphere;
50% With (1,3-dimesitylimidazol-2-ylidene)gold(I) chloride; Selectfluor; p-benzoquinone In 1,2-dichloro-ethane at 80℃; for 24h; Inert atmosphere; Schlenk technique;

  • 23
  • [ 59046-72-9 ]
  • [ 590-86-3 ]
  • [ 2027-17-0 ]
  • (3-isopropylnaphthalen-1-yl)(phenyl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With gold(III) tribromide In 1,4-dioxane at 100℃; for 3h;
In 1,4-dioxane at 100℃; for 3h;
  • 24
  • [ 89-98-5 ]
  • [ 536-74-3 ]
  • [ 59046-72-9 ]
YieldReaction ConditionsOperation in experiment
89% With copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20℃;
87% With nickel(II) ferrite; potassium carbonate In water at 100℃; for 4h; 2.2. General procedure for the Sonogashira reaction 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.
70% With triethylamine In water at 80℃; for 18h;
67% With triethylamine In N,N-dimethyl-formamide at 80℃; for 24h;
54% With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 22h; Green chemistry; 2.5 General method for Sonogashira coupling reaction General procedure: A mixture of aryl halide (1mmol), terminal alkyne (1mmol), K2CO3 (2mmol) and MNPFemTriazNHCAg complex (6) (100mg) in DMF (5mL) was stirred at 100°C. 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.
44% With tetrabutylammomium bromide; C44H68Cl4N12O4Pd2; caesium carbonate In ethanol; water at 80℃; for 10h;
10% With potassium phosphate tribasic trihydrate; C50H40N6O2Pd(2+)*2F6P(1-); tetrabutylammomium bromide In 1,4-dioxane; water at 100℃; for 30h;
84 % Chromat. With triethylamine In toluene at 80℃; for 12h;

  • 25
  • [ 4433-63-0 ]
  • [ 59046-72-9 ]
  • 3-ethyl-2-phenyl-1H-inden-1-ol [ No CAS ]
  • 26
  • [ 59046-72-9 ]
  • [ 106-95-6 ]
  • 1-[2'-(phenylethynyl)phenyl]-3-buten-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With indium In N,N-dimethyl-formamide at 20℃; General procedure for the synthesis of 1-(2-arylalkynylquinolin-3-yl)-but 3-en-1-ols (3) 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.
With aniline; zinc In tetrahydrofuran at 20℃;
  • 27
  • [ 59046-72-9 ]
  • [ 3074-03-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: 0.25 h 2.1: MnO2 / CH2Cl2 / 20 °C 3.1: 61 percent / tetrabutylammonium fluoride / tetrahydrofuran / 0.08 h / 20 °C
Multi-step reaction with 4 steps 1.1: n-BuLi / tetrahydrofuran / -78 °C 1.2: 0.25 h 2.1: MnO2 / CH2Cl2 / 20 °C 3.1: aq. borax / methanol / 20 °C 4.1: 70 percent / benzene / 150 °C
  • 28
  • [ 468751-38-4 ]
  • [ 59046-72-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: TMSOTf 2.1: BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 2.2: tetrahydrofuran; hexane / 1 h / -78 °C 3.1: tetrahydrofuran; hexane / 2 h 4.1: t-BuOK / tetrahydrofuran; hexane / 3.67 h / 0 - 20 °C 5.1: 98 percent / p-TsOH; H2O / acetone / 16 h / 40 °C
Multi-step reaction with 5 steps 1.1: TMSOTf 2.1: BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 2.2: tetrahydrofuran; hexane / 1 h / -78 °C 3.1: tetrahydrofuran; hexane / 1 h / 20 °C 4.1: t-BuOK / tetrahydrofuran; hexane / 1 h / 20 °C 5.1: 98 percent / p-TsOH; H2O / acetone / 16 h / 40 °C
  • 29
  • [ 59046-72-9 ]
  • [ 106-49-0 ]
  • [ 536-74-3 ]
  • [ 1011294-24-8 ]
YieldReaction ConditionsOperation in experiment
88% With copper(I) trifluoromethanesolfonate toluene complex In dichloromethane at 60℃; for 10h; Molecular sieve; 3 Example 3: Preparation of racemic 1-(2-phenylethynyl)-2-(4-methylphenyl)-3-phenyl-1,2-dihydroisoquinoline 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 60°C 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%).
77% With copper(II) sulfate In water ultrasonic conditions;
77% With copper(I) triflate; 2,6-bis((S)-4-isopropyl-4,5-dihydrooxazol-2-yl)pyridine In dichloroethane at 40℃;
  • 30
  • [ 26260-02-6 ]
  • [ 536-74-3 ]
  • [ 59046-72-9 ]
YieldReaction ConditionsOperation in experiment
97% Stage #1: 2-iodobenzaldehyde With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: phenylacetylene In tetrahydrofuran for 18h; Inert atmosphere;
92% With triethylamine In water at 20℃; for 8h; General procedure for the Sonogashira coupling reaction 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.
90% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 14h;
74% With pyrrolidine; copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) In water at 80℃; for 8h;
66% With cetyltrimethylammonim bromide; potassium carbonate In water at 110℃; for 10h; 2.4 General experimental procedure for Sonogashira cross-coupling reaction 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.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; Inert atmosphere;
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 12h; Inert atmosphere;
Stage #1: 2-iodobenzaldehyde With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 23 - 25℃; for 0.25h; Inert atmosphere; Stage #2: phenylacetylene at 50℃; for 4h; Inert atmosphere;
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 16h; Inert atmosphere;
Stage #1: 2-iodobenzaldehyde With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine for 0.0833333h; Inert atmosphere; Stage #2: phenylacetylene With triethylamine at 23 - 25℃; Inert atmosphere;

Reference: [1]Jongcharoenkamol, Jira; Chuathong, Patsapon; Amako, Yuka; Kono, Masato; Poonswat, Kasam; Ruchirawat, Somsak; Ploypradith, Poonsakdi [Journal of Organic Chemistry, 2018, vol. 83, # 21, p. 13184 - 13210]
[2]Keesara, Srinivas; Parvathaneni, Saiprathima; Dussa, Govardhan; Mandapati, Mohan Rao [Journal of Organometallic Chemistry, 2014, vol. 765, p. 31 - 38]
[3]Cinar, M. Emin; Vavilala, Chandrasekhar; Jaquet, Ralph; Bats, Jan W.; Schmittel, Michael [European Journal of Organic Chemistry, 2014, vol. 2014, # 24, p. 5166 - 5177]
[4]Ahammed, Sabir; Dey, Raju; Ranu, Brindaban C. [Tetrahedron Letters, 2013, vol. 54, # 28, p. 3697 - 3701]
[5]Kodicherla, Balaswamy; Perumgani C., Pullaiah; Mandapati, Mohan Rao [Applied Catalysis A: General, 2014, vol. 483, p. 110 - 115]
[6]Wei, Hao; Zhai, Hongbin; Xu, Peng-Fei [Journal of Organic Chemistry, 2009, vol. 74, # 5, p. 2224 - 2226]
[7]Shu, Xing-Zhong; Zhao, Shu-Chun; Ji, Ke-Gong; Zheng, Zhao-Jing; Liu, Xue-Yuan; Liang, Yong-Min [European Journal of Organic Chemistry, 2009, # 1, p. 117 - 122]
[8]Location in patent: body text Vavilala, Chandrasekhar; Bats, Jan W.; Schmittel, Michael [Synthesis, 2010, # 13, p. 2213 - 2222]
[9]Wang, Li-Jing; Zhu, Hai-Tao; Lu, Lei; Yang, Fang; Liu, Xue-Yuan; Liang, Yong-Min [Organic Letters, 2012, vol. 14, # 8, p. 1990 - 1993]
[10]Samanta, Debabrata; Cinar, Mehmet Emin; Das, Kalpataru; Schmittel, Michael [Journal of Organic Chemistry, 2013, vol. 78, # 4, p. 1451 - 1462]
[11]Wang, Jia; Zhu, Hai-Tao; Li, Ying-Xiu; Wang, Li-Jing; Qiu, Yi-Feng; Qiu, Zi-Hang; Zhong, Mei-Jin; Liu, Xue-Yuan; Liang, Yong-Min [Organic Letters, 2014, vol. 16, # 8, p. 2236 - 2239]
  • 31
  • [ 59046-72-9 ]
  • [ 536-74-3 ]
  • [ 22082-92-4 ]
YieldReaction ConditionsOperation in experiment
85% With copper dichloride In nitromethane at 80℃; for 4h; Inert atmosphere;
70% With N-chloro-succinimide; copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane at 80℃; for 8h; Inert atmosphere; regioselective reaction; 4.1. General synthesis of 1-halonaphthalenes 3 General procedure: A solution of 2-(phenylethynyl)benzaldehyde (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.
  • 32
  • [ 59046-72-9 ]
  • [ 536-74-3 ]
  • [ 22082-92-4 ]
  • [ 22082-93-5 ]
YieldReaction ConditionsOperation in experiment
1: 59% 2: 5% With lithium bromide; copper dichloride In acetonitrile at 80℃; for 5h; Inert atmosphere;
  • 33
  • [ 59046-72-9 ]
  • [ 536-74-3 ]
  • [ 22082-93-5 ]
YieldReaction ConditionsOperation in experiment
96% With N-Bromosuccinimide; copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane at 80℃; for 8h; Inert atmosphere; regioselective reaction; 4.1. General synthesis of 1-halonaphthalenes 3 General procedure: A solution of 2-(phenylethynyl)benzaldehyde (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. 1-Bromo-2-phenylnaphthalene (3a)[13]: 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 7.8 Hz, 1H), 7.87-7.66 (m, 2H), 7.65 (dd, J = 8.0, 1.2 Hz, 1H), 7.57 (dd, J = 6.8, 1.2 Hz, 1H), 7.47-7.38 (m, 6H).
62% With copper(ll) bromide In nitromethane at 60℃; for 2h; Inert atmosphere;
  • 34
  • [ 40138-16-7 ]
  • [ 536-74-3 ]
  • [ 59046-72-9 ]
YieldReaction ConditionsOperation in experiment
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; Procedure for the oxidative coupling reaction 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 100°C 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.
79% With pyridine; copper(I) oxide In chloroform at 25℃; for 24h;
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; Typical procedure fortheoxidative coupling reaction 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 100°C 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.
70% With (E)-N-(pyren-1-ylmethylene)benzenamine; oxygen; palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 100℃; for 3h;

  • 35
  • [ 5825-45-6 ]
  • [ 59046-72-9 ]
  • N-[2-(phenylethynyl)benzylidene]-3,4-dihydroquinolin-1(2H)-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With sodium acetate; acetic acid In ethanol at 0 - 20℃;
  • 36
  • [ 32566-01-1 ]
  • [ 59046-72-9 ]
  • [ 1226977-97-4 ]
  • 37
  • [ 32566-01-1 ]
  • [ 59046-72-9 ]
  • [ 1226977-98-5 ]
  • 38
  • [ 5900-59-4 ]
  • [ 59046-72-9 ]
  • [ 1226978-05-7 ]
  • 39
  • [ 59046-72-9 ]
  • [ 40545-33-3 ]
  • [ 1226978-02-4 ]
  • 40
  • [ 59046-72-9 ]
  • [ 115643-59-9 ]
  • [ 1226978-03-5 ]
  • 41
  • [ 59046-72-9 ]
  • [ 24470-78-8 ]
  • [ 59046-69-4 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: isopropyltriphenylphosphonium iodide With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at 0 - 20℃; for 16h; Inert atmosphere;
67% Stage #1: isopropyltriphenylphosphonium iodide With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at 0 - 20℃; Inert atmosphere;
24% Stage #1: isopropyltriphenylphosphonium iodide With n-butyllithium In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; Schlenk technique; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Schlenk technique;
With n-butyllithium In tetrahydrofuran at 0 - 20℃;
Stage #1: isopropyltriphenylphosphonium iodide With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at 0 - 20℃;
Stage #1: isopropyltriphenylphosphonium iodide With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5h; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at 0 - 20℃; Inert atmosphere;

  • 42
  • [ 558-13-4 ]
  • [ 59046-72-9 ]
  • [ 1227172-59-9 ]
YieldReaction ConditionsOperation in experiment
89% Stage #1: carbon tetrabromide With triphenylphosphine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: o-(phenylethynyl)benzaldehyde In dichloromethane for 4h; Inert atmosphere; Schlenk technique;
80% With triisopropyl phosphite In dichloromethane at 20℃; for 15h; Inert atmosphere;
80% Stage #1: carbon tetrabromide With triphenylphosphine; zinc In dichloromethane at 0 - 20℃; for 1.5h; Stage #2: o-(phenylethynyl)benzaldehyde In dichloromethane at 0 - 20℃; for 24h; 4 Preparation of Compound 2-18 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 0°C, 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 0°C, 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.
With triethylamine; triphenylphosphine In dichloromethane at 20℃; for 3h;
With triphenylphosphine In dichloromethane at 0℃; for 0.5h; Inert atmosphere;

  • 43
  • [ 59046-72-9 ]
  • [ 54011-33-5 ]
  • [ 1257647-12-3 ]
YieldReaction ConditionsOperation in experiment
72% With piperidine; acetic acid In toluene for 3h; Reflux; Molecular sieve;
  • 44
  • [ 629-05-0 ]
  • [ 59046-72-9 ]
  • [ 2876-46-2 ]
YieldReaction ConditionsOperation in experiment
92% With toluene-4-sulfonic acid In 1,2-dichloro-ethane at 200℃; for 0.5h; Microwave irradiation; General procedure for the reaction of 2-(phenylethynyl)benzaldehyde (1) and alkynes 2 General procedure: A solution of 2-(phenylethynyl)benzaldehyde (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
61% With zinc(II) chloride In 1,2-dichloro-ethane at 80℃; for 12h; Inert atmosphere; regiospecific reaction;
  • 45
  • [ 59046-72-9 ]
  • [ 108-94-1 ]
  • [ 1268394-65-5 ]
YieldReaction ConditionsOperation in experiment
50% Stage #1: o-(phenylethynyl)benzaldehyde With toluene-4-sulfonic acid hydrazide In ethanol; dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With bromine In ethanol; dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #3: cyclohexanone With potassium phosphate In ethanol at 70℃; Inert atmosphere; Experimental procedure for multi-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, electrophile, and ketone or aldehyde. 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.
  • 46
  • [ 59046-72-9 ]
  • [ 108-94-1 ]
  • [ 1268394-67-7 ]
YieldReaction ConditionsOperation in experiment
62% Stage #1: o-(phenylethynyl)benzaldehyde With toluene-4-sulfonic acid hydrazide In ethanol; dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With iodine In ethanol; dichloromethane at 20℃; for 24h; Inert atmosphere; Stage #3: cyclohexanone With potassium phosphate In ethanol at 70℃; Inert atmosphere; Experimental procedure for multi-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, electrophile, and ketone or aldehyde. 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.
  • 47
  • [ 59046-72-9 ]
  • [ 123-72-8 ]
  • 1-ethyl-6-iodo-5-phenyl-1H,10bH-pyrazolo[5,1-a]isoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: o-(phenylethynyl)benzaldehyde With toluene-4-sulfonic acid hydrazide In ethanol; dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With iodine In ethanol; dichloromethane at 20℃; for 24h; Inert atmosphere; Stage #3: butyraldehyde With potassium phosphate In ethanol at 70℃; Inert atmosphere; Experimental procedure for multi-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, electrophile, and ketone or aldehyde. 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.
  • 48
  • [ 59046-72-9 ]
  • [ 98-86-2 ]
  • 6-bromo-2,5-diphenyl-1H,10bH-pyrazolo[5,1-a]isoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% Stage #1: o-(phenylethynyl)benzaldehyde With toluene-4-sulfonic acid hydrazide In ethanol; dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With bromine In ethanol; dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #3: acetophenone With potassium phosphate In ethanol at 70℃; Inert atmosphere; Experimental procedure for multi-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, electrophile, and ketone or aldehyde. 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.
  • 49
  • [ 59046-72-9 ]
  • [ 96-22-0 ]
  • 6-bromo-2-ethyl-1-methyl-5-phenyl-1H,10bH-pyrazolo[5,1-a]isoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% Stage #1: o-(phenylethynyl)benzaldehyde With toluene-4-sulfonic acid hydrazide In ethanol; dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With bromine In ethanol; dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #3: pentan-3-one With potassium phosphate In ethanol at 70℃; Inert atmosphere; Experimental procedure for multi-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, electrophile, and ketone or aldehyde. 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.
  • 50
  • [ 59046-72-9 ]
  • [ 14114-05-7 ]
  • [ 1263056-63-8 ]
  • 51
  • [ 288-32-4 ]
  • [ 59046-72-9 ]
  • [ 62-53-3 ]
  • [ 1284223-22-8 ]
YieldReaction ConditionsOperation in experiment
87% With silver trifluoromethanesulfonate In toluene at 70℃; Inert atmosphere; 4.1. General procedure for AgOTf-catalyzed three-component reactions of 2-alkynylbenzaldehyde 1, amine 2, and imidazole 3 General procedure: Imidazole 3 (1.0 mmol, 2.0 equiv) and AgOTf (0.025 mmol, 5 mol %) were added to a mixture of 2-alkynylbenzaldehyde 1 (0.5 mmol) and amine 2 (0.5 mmol, 1.0 equiv) in toluene (2.0 mL). The reaction mixture was stirred at 70 °C vigorously until completion of the reaction. Subsequently, 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 in vacuo. The residue was purified by column chromatography on silica gel to provide the desired product I.
  • 52
  • [ 822-36-6 ]
  • [ 59046-72-9 ]
  • [ 62-53-3 ]
  • [ 1284223-27-3 ]
YieldReaction ConditionsOperation in experiment
67% With silver trifluoromethanesulfonate In toluene at 70℃; Inert atmosphere; 4.1. General procedure for AgOTf-catalyzed three-component reactions of 2-alkynylbenzaldehyde 1, amine 2, and imidazole 3 General procedure: Imidazole 3 (1.0 mmol, 2.0 equiv) and AgOTf (0.025 mmol, 5 mol %) were added to a mixture of 2-alkynylbenzaldehyde 1 (0.5 mmol) and amine 2 (0.5 mmol, 1.0 equiv) in toluene (2.0 mL). The reaction mixture was stirred at 70 °C vigorously until completion of the reaction. Subsequently, 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 in vacuo. The residue was purified by column chromatography on silica gel to provide the desired product I.
  • 53
  • [ 59046-72-9 ]
  • [ 1080-32-6 ]
  • [ 59046-63-8 ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: O,O-diethyl benzylphosphonate With sodium hexamethyldisilazane In tetrahydrofuran; hexane at -78 - 20℃; for 0.5h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at -50 - 20℃;
87% Stage #1: O,O-diethyl benzylphosphonate With sodium hydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran at 0 - 20℃; for 6h; Inert atmosphere;
Stage #1: O,O-diethyl benzylphosphonate With sodium hexamethyldisilazane In tetrahydrofuran; hexane at -78 - 20℃; for 0.5h; Stage #2: o-(phenylethynyl)benzaldehyde In tetrahydrofuran; hexane at 20℃;
  • 54
  • [ 40138-16-7 ]
  • [ 932-87-6 ]
  • [ 59046-72-9 ]
YieldReaction ConditionsOperation in experiment
86% With copper(l) iodide; 8-quinolinol; sodium phosphate In ethanol at 80℃; for 24h; 4.2. General procedure for CuI-catalyzed Suzuki coupling reaction of organoboronic acids with alkynyl bromides General procedure: A 5.0 mL of reaction tube was charged with organoboron compound (1.0 mmol), alkynyl bromide (1.0 mmol), CuI (0.10 mmol), 8-hydroxyquinoline (0.20 mmol), ethanol (2.0 mmol). The mixture was stirred at 80 °C for 24 h, and then washed with ethyl acetate (3.0 mL×3), the combined ethyl acetate was concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (petroleum ether as eluting agent) to give the corresponding pure cross-coupling product.
  • 55
  • [ 591-50-4 ]
  • [ 38846-64-9 ]
  • [ 59046-72-9 ]
YieldReaction ConditionsOperation in experiment
70% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 80℃; for 1h; Inert atmosphere; 4.2.1. 2-[(2-Bromophenyl)ethynyl]benzaldehyde (1a) General procedure: A mixture of 2-ethynylbenzaldehyde (12a) (1.00 g, 7.68 mmol), 1-bromo-2-iodo-benzene (13a) (1.18 mL, 9.22 mmol), CuI (146 mg, 0.77 mmol), PdCl2(PPh3)2 (107 mg, 0.15 mmol), and Et3N (15 mL) in THF (15 mL) was stirred at 80 °C for 2 h under argon, and filtrated through a pad of Celite. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography over silica gel with hexane-EtOAc (15:1).
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere;
  • 56
  • [ 59046-72-9 ]
  • [ 479-27-6 ]
  • [ 1314582-64-3 ]
YieldReaction ConditionsOperation in experiment
91% With copper(l) iodide In 1,4-dioxane at 150℃; for 1h; Microwave irradiation; 4.3.1. General procedure: synthesis of 13-(2-Bromophenyl)-7,7a,12,13-dihydroisoquinolino[2,1-a]perimidine (3a) (Table 1, entry 6) General procedure: A mixture of 1a (50 mg, 0.18 mmol), 1,8-diaminonaphthalene (2) (41.5 mg, 0.26 mmol), and CuI (3.3 mg, 0.018 mmol) in dioxane (1.0 mL) was stirred for 60 min at 150 °C under microwave irradiation (300 W). The reaction mixture was concentrated under reduced pressure and purified by column chromatography over silica gel with hexane-EtOAc (15:1).
  • 57
  • [ 6914-71-2 ]
  • [ 59046-72-9 ]
  • [ 1576-35-8 ]
  • [ 1338721-71-3 ]
  • 58
  • [ 726-42-1 ]
  • [ 59046-72-9 ]
  • [ 1576-35-8 ]
  • [ 1322091-54-2 ]
YieldReaction ConditionsOperation in experiment
88% With silver trifluoromethanesulfonate In 1,2-dichloro-ethane at 50 - 60℃; Inert atmosphere; General procedure for AgOTf-catalyzed three-component reaction of 2-alkynylbenzaldehyde 1, sulfonohydrazide, with carbodiimide 2. General procedure: Silver triflate (0.02 mmol, 10 mol %) was added to a solution of 2-alkynylbenzaldehyde 1 (0.2 mmol), sulfonohydrazide (0.2 mmol), and carbodiimide compound 2 (0.4 mmol, 2.0 equiv) in DCE (2.0 mL). The solution was stirred at 50-60 °C for overnight. After completion of reaction as indicated by TLC, the reaction was quenched by addition of saturated aqueous NH4Cl (5.0 mL), and the mixture was extracted with EtOAc (4.0 mL×3). The combined organic layer was dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel to provide the desired product 3.
  • 59
  • [ 838-98-2 ]
  • [ 59046-72-9 ]
  • [ 1576-35-8 ]
  • [ 1322091-61-1 ]
YieldReaction ConditionsOperation in experiment
88% With silver trifluoromethanesulfonate In 1,2-dichloro-ethane at 50 - 60℃; Inert atmosphere; General procedure for AgOTf-catalyzed three-component reaction of 2-alkynylbenzaldehyde 1, sulfonohydrazide, with carbodiimide 2. General procedure: Silver triflate (0.02 mmol, 10 mol %) was added to a solution of 2-alkynylbenzaldehyde 1 (0.2 mmol), sulfonohydrazide (0.2 mmol), and carbodiimide compound 2 (0.4 mmol, 2.0 equiv) in DCE (2.0 mL). The solution was stirred at 50-60 °C for overnight. After completion of reaction as indicated by TLC, the reaction was quenched by addition of saturated aqueous NH4Cl (5.0 mL), and the mixture was extracted with EtOAc (4.0 mL×3). The combined organic layer was dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel to provide the desired product 3.
  • 60
  • [ 1006619-83-5 ]
  • [ 59046-72-9 ]
  • [ 1364406-03-0 ]
  • (R)-8-chloro-4b,5-dihydro-10-methyl-12-phenylisoquinolino[2,1-a]quinazolin-6-one [ No CAS ]
  • C23H17ClN2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With methyl(triphenylphosphine)gold(I); (S)-3,3'-bis(9-anthracenyl)-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate In 1,2-dichloro-ethane at -5 - 20℃; for 80h; Molecular sieve; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
  • 61
  • [ 5900-59-4 ]
  • [ 59046-72-9 ]
  • [ 1364405-97-9 ]
  • 62
  • [ 59046-72-9 ]
  • [ 54166-95-9 ]
  • [ 1364405-95-7 ]
  • (R)-7-chloro-4b,5-dihydro-12-phenylisoquinolino[2,1-a]quinazolin-6-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With methyl(triphenylphosphine)gold(I); (S)-3,3'-bis(9-anthracenyl)-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate In 1,2-dichloro-ethane at -5 - 20℃; for 80h; Molecular sieve; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
  • 63
  • [ 59046-72-9 ]
  • [ 1882-71-9 ]
  • [ 1364405-99-1 ]
  • 64
  • [ 59046-72-9 ]
  • [ 115643-59-9 ]
  • [ 1364405-93-5 ]
  • (R)-7-fluoro-4b,5-dihydro-12-phenylisoquinolino[2,1-a]quinazolin-6-one [ No CAS ]
  • 65
  • [ 59046-72-9 ]
  • [ 1187397-44-9 ]
  • [ 37993-76-3 ]
  • 66
  • [ 504-29-0 ]
  • [ 106106-81-4 ]
  • [ 59046-72-9 ]
  • [ 2923-28-6 ]
  • 13-[(3-chlorobenzyl)amino]-6-phenylpyrido[2',1':2,3]imidazo[5,1-a]-isoquinolinium trifluoromethanesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: 2-aminopyridine; 1-chloro-3-(isocyanomethyl)benzene; o-(phenylethynyl)benzaldehyde With ytterbium(III) triflate In tetrahydrofuran at 55℃; for 12h; Stage #2: silver trifluoromethanesulfonate In tetrahydrofuran at 55℃; for 1h;
  • 67
  • [ 59046-72-9 ]
  • [ 22884-29-3 ]
  • [ 1398121-29-3 ]
  • [ 1398121-30-6 ]
  • 68
  • [ 59046-72-9 ]
  • [ 536-74-3 ]
  • [ 612-94-2 ]
  • [ 22082-93-5 ]
YieldReaction ConditionsOperation in experiment
With copper(ll) bromide In nitromethane at 60℃; for 2h; Inert atmosphere; Overall yield = 232 mg; 3-1. Synthesis of 4,4,5,5-Tetramethyl-2-(2-phenyl-naphthalen-1-yl)-[1,3,2]dioxaborolane A solution of o-(2-phenylethynyl)benzaldehyde (1.00 mmol, 0.207 g) and CuBr2 (2.00 mmol. 0.447 g) in CH3NO2 (3.0 mL) was stirred under an argon atmosphere at room temperature.S2) Phenyl acetylene (1.20 mmol, 0.123 g) was added to the reaction mixture and the resulting mixture was heated at 60 ˚C for 2 h under an argon atmosphere. Another run of the same scale was carried out. The both reaction mixtures were combined, and the resulting mixture was evaporated and purified by silica gel column chromatography (n-hexane). The products were further purified by preparative HPLC to afford the inseparable mixture of 1-bromo-2-phenylnaphthalene and 2-phenylnaphthalene (232 mg, 1-bromo-2-phenylnaphthalene : 2-phenylnaphthalene = 66 : 34). This mixture was used in the next step. To the solution of the above mixture in THF (5.0 mL) was slowly added a solution of n-BuLi in hexane (0.4 mL, 1.6 M) at -78 °C under an argon atmosphere. After being stirred for 30 min, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (120 mg, 0.65 mmol) was added to the reaction mixture. The mixture was stirred for 1 h at -78 °C and then slowly warmed to room temperature. After being stirred for 2 h at room temperature, H2O was added to the mixture, and the resulting mixture was extracted with CHCl3. The organic layer was washed with brine and dried over anhydrous MgSO4. After removal of the solvent under reduced pressure, purification by chromatography (n-hexane : AcOEt = 19 : 1) gave 4,4,5,5-tetramethyl-2-(2-phenyl-naphthalen-1-yl)-[1,3,2]dioxaborolaneS3) (99 mg, 0.30 mmol, yield 15% for two steps).
1: 28 %Spectr. 2: 8 %Spectr. With N-Bromosuccinimide; copper(II) bis(trifluoromethanesulfonate) In hexane at 80℃; for 8h; Inert atmosphere; regioselective reaction; 4.1. General synthesis of 1-halonaphthalenes 3 General procedure: A solution of 2-(phenylethynyl)benzaldehyde (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. 1-Bromo-2-phenylnaphthalene (3a)S1: 1H-NMR (400 MHz, CDCl3) δ 8.42 (d, J = 7.8 Hz, 1H), 7.87-7.66 (m, 2H), 7.65 (dd, J = 8.0, 1.2 Hz, 1H), 7.57 (dd, J = 6.8, 1.2 Hz, 1H), 7.47-7.38 (m, 6H).
  • 69
  • [ 59046-72-9 ]
  • [ 748805-85-8 ]
  • [ 1428747-18-5 ]
  • 70
  • [ 59046-72-9 ]
  • [ 37585-16-3 ]
  • [ 1428747-25-4 ]
  • 71
  • [ 59046-72-9 ]
  • [ 20712-12-3 ]
  • [ 1428747-27-6 ]
  • 72
  • [ 59046-72-9 ]
  • [ 23612-57-9 ]
  • [ 1428747-76-5 ]
  • 73
  • [ 59046-72-9 ]
  • [ 28144-70-9 ]
  • [ 1469993-57-4 ]
YieldReaction ConditionsOperation in experiment
92% With iodine; potassium carbonate; sodium sulfate In acetonitrile at 20℃; for 3h; General procedure for the iodine-mediated reaction of 2-alkynylbenzaldehydes (1) and 2-aminobenzamides (4) as exemplified by the preparation of 5aA1 General procedure for the iodine-mediated reaction of 2-alkynylbenzaldehydes (1) and 2-aminobenzamides (4) as exemplified by the preparation of 5aA1 To a stirred solution of 1aA (0.42 g, 2.0 mmol), 41 (0.272 g, 2.0 mmol) in MeCN (15 mL) were added I2 (0.762 g, 3.0 mmol), K2CO3 (0.414 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g, 2.0 mmol) at room temperature. The reaction was allowed to proceed at room temperature until complete consumption of starting material as monitored by TLC (ca. 3 h). Thereafter saturated Na2S2O3 aqueous solution was added; the solid precipitate was filtered and dried to give 5aA1.
76% With iodine In 1,2-dichloro-ethane at 20℃; for 8h; Inert atmosphere;
  • 74
  • [ 1006619-83-5 ]
  • [ 59046-72-9 ]
  • [ 1469886-57-4 ]
YieldReaction ConditionsOperation in experiment
84% With iodine In 1,2-dichloro-ethane at 20℃; for 3h; Inert atmosphere;
  • 75
  • [ 59046-72-9 ]
  • [ 118-92-3 ]
  • C22H14INO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With iodine; sodium hydrogencarbonate; sodium sulfate In acetonitrile at 20℃; for 5h; 1 General procedure for the iodine-mediated reaction of 2-alkynylbenzaldehydes 1 and anthranilic acid 2 as exemplified by the preparation of 3aAa To a stirred mixture of 1aA (0.42 g, 2.0 mmol) and 2a (0.279 g, 2.0 mmol) in MeCN (15 mL) were added NaHCO3 (0.252 g, 3.0 mmol), I2 (0.762 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g, 2.0 mmol) at room temperature. The reaction was allowed to proceed at room temperature until complete consumption of starting material as monitored by TLC (ca. 5 h). After the reaction was complete, the mixture was washed with saturated Na2S2O3 solution, extracted with EtOAc (2×25 mL), dried over anhydrous Na2SO4, and evaporated in vacuum on a rotary evaporator to afford a residue. This residue was purified by column chromatography on silica gel using hexanes-EtOAc (70:30, v/v) as the eluent to furnish 0.85 g (94%) of 3aAa as a white solid. 4.2.1 Iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11(16),12,14,17-eptaen-8-one (3aAa) Mp: 142-143 °C; Rf=0.65 (CH2Cl2-MeOH, 9.5:0.5, v/v); IR (KBr) ν: 1722, 1592, 1464, 1280, 758 cm-1. 1H NMR (300 MHz, CDCl3): δ (ppm)=6.44 (d, 1H, J=7.8 Hz, ArH), 6.89 (s, 1H, CH), 7.08-7.19 (m, 4H, ArH), 7.26-7.29 (m, 3H, ArH), 7.38-7.46 (m, 2H, ArH), 7.57 (t, 1H, J=6.6 Hz, ArH), 7.74 (d, 1H, J=8.1 Hz, ArH), 8.07 (dd, 1H, J1=1.4 Hz, J2=7.5 Hz, ArH); 13C NMR (75 MHz, CDCl3): δ (ppm)=89.5, 122.7, 123.5, 124.7, 126.2, 127.9, 128.2, 128.5, 128.9, 129.1, 130.1, 123.6, 131.1, 131.4, 132.9, 133.3, 138.7, 142.3, 144.2, 163.5. MS (ESI+): m/z=452.0. ESI-HRMS calculated for C22H14INO2 [MH]+: 452.0147, found: 452.0143.
  • 76
  • [ 59046-72-9 ]
  • [ 446-32-2 ]
  • 4-fluoro-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With iodine; sodium hydrogencarbonate; sodium sulfate In acetonitrile at 20℃; for 5h; 2 General procedure: To a stirred mixture of 1aA (0.42 g, 2.0 mmol) and 2a (0.279 g, 2.0 mmol) in MeCN (15 mL) were added NaHCO3 (0.252 g, 3.0 mmol), I2 (0.762 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g, 2.0 mmol) at room temperature. The reaction was allowed to proceed at room temperature until complete consumption of starting material as monitored by TLC (ca. 5 h). After the reaction was complete, the mixture was washed with saturated Na2S2O3 solution, extracted with EtOAc (2×25 mL), dried over anhydrous Na2SO4, and evaporated in vacuum on a rotary evaporator to afford a residue. This residue was purified by column chromatography on silica gel using hexanes-EtOAc (70:30, v/v) as the eluent to furnish 0.85 g (94%) of 3aAa as a white solid. 4.2.2 4-Fluoro-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one (3aAb) Yield: 84% (0.78 g from 0.42 g) as a gray solid, mp: 156-158 °C; Rf=0.68 (CH2Cl2-MeOH, 9.5:0.5, v/v); IR (KBr) ν: 1726, 1292, 788 cm-1. 1H NMR (300 MHz, CDCl3): δ (ppm)=6.15 (d, 1H, J=8.7 Hz, ArH), 6.87 (d, 1H, J=8.1 Hz, ArH), 7.11 (s, 2H, CH), 7.26-7.61 (m, 7H, ArH), 7.76 (d, 1H, J=7.2 Hz, ArH), 8.06 (s, 1H, ArH); 13C NMR (75 MHz, CDCl3): δ (ppm)=90.6, 100.8, 103.9, 112.4 (d, J=25.5 Hz), 114.5 (d, J=22.5 Hz), 123.3, 125.6(2C), 128.7, 129.2, 130.2, 131.6, 132.8, 134.5, 134.9, 142.9, 145.6, 151.7, 153.2, 153.5158.5, 162.9. MS (ESI+): m/z=470.0. ESI-HRMS calculated for C22H13FINO2 [MH]+: 470.0053, found: 470.0034.
  • 77
  • [ 20776-50-5 ]
  • [ 59046-72-9 ]
  • 4-bromo-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With iodine; sodium hydrogencarbonate; sodium sulfate; In acetonitrile; at 20℃; for 5h; General procedure: To a stirred mixture of 1aA (0.42 g, 2.0 mmol) and 2a (0.279 g, 2.0 mmol) in MeCN (15 mL) were added NaHCO3 (0.252 g, 3.0 mmol), I2 (0.762 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g, 2.0 mmol) at room temperature. The reaction was allowed to proceed at room temperature until complete consumption of starting material as monitored by TLC (ca. 5 h). After the reaction was complete, the mixture was washed with saturated Na2S2O3 solution, extracted with EtOAc (2×25 mL), dried over anhydrous Na2SO4, and evaporated in vacuum on a rotary evaporator to afford a residue. This residue was purified by column chromatography on silica gel using hexanes-EtOAc (70:30, v/v) as the eluent to furnish 0.85 g (94%) of 3aAa as a white solid. 4.2.3 4-Bromo-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one (3aAc) Yield: 92% (0.97 g from 0.42 g) as a white solid, mp: 163-165 C; Rf=0.68 (CH2Cl2-MeOH, 9.5:0.5, v/v); IR (KBr) nu: 1721, 1593, 1385, 1075, 765 cm-1. 1H NMR (300 MHz, CDCl3): delta (ppm)=6.65 (s, 1H, ArH), 6.99 (s, 1H, CH), 7.15 (s, 2H, ArH), 7.32-7.51 (m, 6H, ArH), 7.64 (d, 1H, J=6.5 Hz, ArH), 7.82 (d, 1H, J=7.9 Hz, ArH), 7.96 (d, 1H, J=8.3 Hz, ArH); 13C NMR (75 MHz, CDCl3): delta (ppm)=89.4, 120.6, 127.5, 128.1, 128.3, 128.5, 128.7, 129.6(4C), 130.5(3C), 131.2(2C), 131.3, 131.6, 133.2, 138.2, 144.7, 162.8. MS (ESI+): m/z=530.2. ESI-HRMS calculated for C22H13BrINO2 [MH]+: 529.9253, found: 529.9233.
  • 78
  • [ 59046-72-9 ]
  • [ 5794-88-7 ]
  • 5-bromo-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With iodine; sodium hydrogencarbonate; sodium sulfate In acetonitrile at 20℃; for 5h; 4 General procedure: To a stirred mixture of 1aA (0.42 g, 2.0 mmol) and 2a (0.279 g, 2.0 mmol) in MeCN (15 mL) were added NaHCO3 (0.252 g, 3.0 mmol), I2 (0.762 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g, 2.0 mmol) at room temperature. The reaction was allowed to proceed at room temperature until complete consumption of starting material as monitored by TLC (ca. 5 h). After the reaction was complete, the mixture was washed with saturated Na2S2O3 solution, extracted with EtOAc (2×25 mL), dried over anhydrous Na2SO4, and evaporated in vacuum on a rotary evaporator to afford a residue. This residue was purified by column chromatography on silica gel using hexanes-EtOAc (70:30, v/v) as the eluent to furnish 0.85 g (94%) of 3aAa as a white solid. 4.2.4 5-Bromo-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one (3aAd) Yield: 86% (0.91 g from 0.42 g) as a white solid, mp: 176-178 °C; Rf=0.67 (CH2Cl2-MeOH, 9.5:0.5, v/v); IR (KBr) ν: 1726, 1266, 1096, 703 cm-1. 1H NMR (300 MHz, CDCl3): δ (ppm)=5.92 (d, 1H, J=8.5 Hz, ArH), 6.13-3.38 (m, 5H, ArH), 6.41 (d, 1H, J=1.7 Hz, ArH), 6.72-6.77 (m, 1H, ArH), 6.88 (s, 1H, ArH), 6.96-7.02 (m, 3H, ArH), 7.77 (s, 1H, ArH); 13C NMR (75 MHz, DMSO): δ (ppm)=91.6, 121.2, 124.2, 128.4(2C), 128.5(3C), 129.8(2C), 130.1, 130.6, 131.4, 131.7, 132.6, 133.8, 135.8, 136.7, 137.3, 141.8, 145.8, 162.7. MS (ESI+): m/z=530.1. ESI-HRMS calculated for C22H13INO2 [MH]+: 529.9253, found: 529.9248.
  • 79
  • [ 59046-72-9 ]
  • [ 89-77-0 ]
  • 4-chloro-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With iodine; sodium hydrogencarbonate; sodium sulfate In acetonitrile at 20℃; for 5h; 5 General procedure: To a stirred mixture of 1aA (0.42 g, 2.0 mmol) and 2a (0.279 g, 2.0 mmol) in MeCN (15 mL) were added NaHCO3 (0.252 g, 3.0 mmol), I2 (0.762 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g, 2.0 mmol) at room temperature. The reaction was allowed to proceed at room temperature until complete consumption of starting material as monitored by TLC (ca. 5 h). After the reaction was complete, the mixture was washed with saturated Na2S2O3 solution, extracted with EtOAc (2×25 mL), dried over anhydrous Na2SO4, and evaporated in vacuum on a rotary evaporator to afford a residue. This residue was purified by column chromatography on silica gel using hexanes-EtOAc (70:30, v/v) as the eluent to furnish 0.85 g (94%) of 3aAa as a white solid. 4.2.5 4-Chloro-17-iodo-18-phenyl-9-oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-one (3aAe) Yield: 90% (0.87 g from 0.42 g) as a white solid, mp: 198-200 °C; Rf=0.65 (CH2Cl2-MeOH, 9.5:0.5, v/v); IR (KBr) ν: 1725, 1591, 1424, 1262, 1088, 705 cm-1. 1H NMR (300 MHz, CDCl3): δ (ppm)=6.43 (d, 1H, J=1.1 Hz, ArH), 6.93 (s, 1H, CH), 7.12-7.15 (m, 3H, ArH), 7.34-7.45 (m, 5H, ArH), 7.59 (t, 1H, J=7.2 Hz, ArH), 7.76 (d, 1H, J=7.9 Hz, ArH), 7.98 (d, 1H, J=8.4 Hz, ArH); 13C NMR (75 MHz, CDCl3): δ (ppm)=90.2, 121.6, 122.7(2C), 126.7, 128.3, 128.6(4C), 130.5(2C), 131.2, 131.7(2C), 133.2, 138.2, 139.2, 139.4, 141.7, 144.8, 162.7. MS (ESI+): m/z=486.1. ESI-HRMS calculated for C22H13ClINO2 [MH]+: 485.9758, found: 485.9740. The details of the crystal structure investigation of this compound can be obtained from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK vide CCDC no. 956063.
  • 80
  • [ 59046-72-9 ]
  • [ 5680-80-8 ]
  • [ 1533409-53-8 ]
  • [ 37993-76-3 ]
YieldReaction ConditionsOperation in experiment
52%; 40% With gold(III) chloride; triethylamine; In 1,2-dichloro-ethane; at 70℃;Schlenk technique; Sealed tube; Inert atmosphere; General procedure: An oven-dried Schlenk tube with a Teflon screw valvewas charged with 1.1 equiv of L(-)Amino ester hydrochloride 2a-b,DCE (1,2-dichloroethane) (2.0 mL), 1.1 equiv Et3N, 0.5 mmol of the 2-alkanylaldehyde 1a-i, and AuCl3(10 mol %). The Schlenk tube was capped with a rubber septum and then evacuatedand backfilled with nitrogen. The septum was then replaced with a Teflon screw valve,and the Schlenk tube was sealed. The reaction mixture was heated to 70 C until2-alkanylaldehyde 1a-i had been completelyconsumed (as determined by TLC) and was allowed to cool to room temperature.The reaction mixture was diluted with ethyl acetate (10 mL) and water (15 mL).Organic layer was concentrated under reduced pressure. The crude material soobtained was purified by column chromatography on silica gel. Reaction wascarried out without Et3N when S (+) phenyl glycinol 2c isused.
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