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CAS No. : | 10486-61-0 | MDL No. : | MFCD00037901 |
Formula : | C4H3IS | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | WGKRMQIQXMJVFZ-UHFFFAOYSA-N |
M.W : | 210.04 | Pubchem ID : | 66332 |
Synonyms : |
|
Num. heavy atoms : | 6 |
Num. arom. heavy atoms : | 5 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 37.04 |
TPSA : | 28.24 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.71 cm/s |
Log Po/w (iLOGP) : | 1.96 |
Log Po/w (XLOGP3) : | 2.63 |
Log Po/w (WLOGP) : | 2.35 |
Log Po/w (MLOGP) : | 2.18 |
Log Po/w (SILICOS-IT) : | 3.69 |
Consensus Log Po/w : | 2.56 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.42 |
Solubility : | 0.0806 mg/ml ; 0.000384 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.87 |
Solubility : | 0.281 mg/ml ; 0.00134 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.62 |
Solubility : | 0.5 mg/ml ; 0.00238 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.61 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: 3-Bromothiophene With n-butyllithium In hexane at -70℃; Inert atmosphere; Stage #2: In tetrahydrofuran; hexane at -70 - 0℃; Inert atmosphere; Stage #3: With 1,2-Diiodoethane In tetrahydrofuran; hexane at -70 - 20℃; Inert atmosphere; chemoselective reaction; | |
86% | Stage #1: 3-Bromothiophene With n-butyllithium In hexane at -70 - 0℃; for 0.5h; Inert atmosphere; Stage #2: With 1,2-Diiodoethane In hexane at -70 - 20℃; for 1h; Inert atmosphere; | |
84% | With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine In 1,4-dioxane at 110℃; for 24h; Inert atmosphere; |
80% | With copper(l) iodide; N,N-dimethylethylenediamine; sodium iodide In 5,5-dimethyl-1,3-cyclohexadiene; diethylene glycol dimethyl ether at 110℃; Inert atmosphere; | |
75% | With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine In 1,4-dioxane at 110℃; for 24h; Inert atmosphere; | |
With n-butyllithium; iodine | ||
With n-butyllithium; 1,2-Diiodoethane 1.) THF, hexane, -40 deg C; 2.) THF, hexane, r.t.; Yield given. Multistep reaction; | ||
83 %Chromat. | Stage #1: 3-Bromothiophene With indium; bathophenanthroline; 3-chloroprop-1-ene; lithium chloride; cobalt(II) bromide In tetrahydrofuran at 80℃; for 18h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; | |
With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine In 5,5-dimethyl-1,3-cyclohexadiene; diethylene glycol dimethyl ether | ||
88 %Chromat. | With copper(I) oxide; <i>L</i>-proline; potassium iodide In ethanol at 110℃; for 30h; Schlenk technique; Inert atmosphere; Sealed tube; | 2.2. General procedure for aryl and heteroaryl bromide-iodideexchange reaction General procedure: A Schlenk tube was charged with Cu2O (7.2 mg, 10 mol%), l-proline (11.5 mg, 20 mol%), aryl (or heteroaryl) bromide (1 or 3,0.50 mmol), potassium iodide (KI) (249 mg, 0.75 mmol), and EtOH(1.5 mL) under nitrogen atmosphere. The Schlenk tube was sealedwith a teflon valve, and then the reaction mixture was stirred at110C for a period (the reaction progress was monitored by GCanalysis). After the reaction was completed, GC yield of high volatileproduct was determined using an appropriate internal standard(chlorobenzene or 1-chloro-4-methylbenzene) or the solvent wasremoved under reduced pressure. The residue obtained was puri-fied via silica gel chromatography (eluent: petroleum ether/ethylacetate = 10/1) to afford aryl iodides 2a-2o or heteroaryl iodides4a-4g. |
10.31 g | With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine In 1,4-dioxane at 110℃; for 24h; Inert atmosphere; Sealed tube; | 3.2. 3-iodothiophene (3) 3.2.1. Method A In a 100 mL reactor, stoppered with rubber septum andflushed with argon, CuI (0.584 g, 3.07 mmol, 0.05 eq.) andNaI (18.39 g 123 mmol, 2 eq.) were introduced and flushed with argon. The xylene (40 mL) and the dioxane (10 mL),previously flushed with argon for 20 min, were introduced.The N,N'-dimethylethylendiamine (0.541 g, 0.600 mL, 6.13mmol, 0.1 eq.) and the 3-bromothiophene (10.00 g, 61.3mmol, 1 eq.) were added. The suspension was degassed withargon for 10 min and it was introduced into the oil bath,warmed at 110°C. The reaction was checked by GC andstopped after 24 h. The suspension was filtered on a Buchner,and the solid was washed with dichloromethane. The mostvolatile solvents were removed under vacuum with a Claisenapparatus working at rt, and the highest boiling solvent (xylene)was removed in the same apparatus by warming from rtto 65-70°C as a maximum, to minimize product losses.A brownish oil was obtained, that was purified by Biotageflash chromatography on silica with petroleum ether,giving a faint yellow oil, 10.31 g (82%). 1H NMR (200 MHz, CDCl3) δ 7.41 (dd, J = 3.0, 1.2 Hz,1H, H-2), 7.20 (dd, J = 5.0, 3.0 Hz, 1H, H-4), 7.10 (dd, J =5.0, 1.2 Hz, 1H, H-5). 13C NMR (50 MHz, CDCl3) δ 134.87(C-4), 128.76 (C-2), 127.43 (C-5), 77.25 (C-3). MS (EI,m/z): 209.18. Elemental analysis: required for C4H3IS, C22.87, H 1.44, S 15.27, found: C 22.93, H 1.39, S 15.22. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sulfuric acid; iodine; iodic acid; acetic acid In hexane; water at 40℃; for 15h; | 6 Example 6: Synthesis of a 2,3-diiodothiophene (hexane solvent) In a 30-mL four mouth flask, 3-iodothiophene (2 g, 9.5mmol), Iodine (0.87 g, 3.4mmol), iodic acid (0.35 g, 2.0mmol), acetic acid (4 mL), n-hexane (6 mL), water (1.5 mL), and concentrated sulfuric acid (two drops) were added, and it was made to react at 40 degrees C for 15 hours. After ending reaction, after cooling to a room temperature, a saturated sodium bicarbonate aqueous solution (10 mL) and diethylether (10 mL) were added and extracted. The sodium-hydrogen-sulfite aqueous solution (10 mL) and the saturated sodium chloride solution solution (10 mL) washed the obtained organic layer in order 10%, and it dried with magnesium sulfate. By refining the gift obtained by filtration and concentration with column chromatography (silica gel: hexane solvent), the 2,3-diiodothiophene was obtained as a substantially colorless liquid at 2.5 g (78% of yield). |
With iodine; iodic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique; | |
99% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique; | |
80% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In diethylamine |
207.3 mg | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In diethylamine; N,N-dimethyl-formamide at 120℃; for 0.0833333h; microwave irradiation; | |
With bis-triphenylphosphine-palladium(II) chloride; triethylamine; copper(l) chloride In dimethyl sulfoxide at 20℃; for 1h; Inert atmosphere; | 3. General procedure for the Sonogashira-Glaser cyclization sequence General procedure: A mixture of a (hetero)aryl iodide 3 (2.00 mmol), PdCl2(PPh3)2 (28.1 mg, 0.04 mmol,2 mol %), and CuCl (7.92 mg, 0.08 mmol, 4 mol %) was dissolved in DMSO (2.00mL) in a 80 mL microwave vessel equipped with a stirring bar and a septum and was degassed with N2 for 5 min. After addition of trimethylsilylacetylene (0.42 mL,3.00 mmol) and dry triethylamine (0.55 mL, 4.00 mmol) the solution was stirred atroom temperature for 1 h. | |
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) at 20℃; for 3h; Inert atmosphere; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Schlenk technique; Inert atmosphere; | Synthesis of substrates 1,2-diphenylethyne derivatives General procedure: Chapter one: A 100 mL schlenk tube was charged with iodobenzene (3.0 mmol), ethynyltrimethylsilane (3.6 mmol), PdCl2(PPh3)2 (0.15 mmol), CuI (0.15 mmol), Et3N:THF = 3:2 (10.0 mL). Then the tube was charged with nitrogen, and was stirred at room temperature for the indicated time until complete consumption of starting material as monitored by TLC analysis. After the completion of the reaction, then the reaction mxtuire was filtered and the filtrate diluted in ethyl acetate and washed with water. The combined organic layers were dried over anhydrous Na2SO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography (petroleum ether unless otherwise noted) to give the corresponding trimethyl(phenylethynyl)silanes, and used for the next reaction. | |
Stage #1: 3-thienyl iodide With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: trimethylsilylacetylene at 20℃; for 4h; Schlenk technique; Inert atmosphere; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine at 60℃; for 1h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; trifuran-2-yl-phosphane; triethylamine In tetrahydrofuran at 60℃; for 9h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triphenyl phosphite; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 60℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With palladium diacetate; trifuran-2-yl-phosphane; caesium carbonate In acetonitrile at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With 1,2-dimethoxyethane; silver carbonate In xylene at 200℃; for 0.5h; microwave irradiation; | |
52% | With silver carbonate In 1,2-dimethoxyethane; m-xylene at 200℃; for 0.5h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With 2-(2-methyl-1-oxopropane)cyclohexanone; caesium carbonate In N,N-dimethyl-formamide at 20℃; for 17h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With triethylsilane; palladium diacetate; sodium hydrogencarbonate; sodium carbonate at 20℃; for 48h; | General Procedure A for reductive carbonylation of aryl iodide to aromatic aldehyde underambient conditions. General procedure: A flask was charged with aryl iodide 1 (0.5 mmol), Pd(OAc)2 (2.4 mg, 0.01mmol), Na2CO3 (53.1 mg. 0.5 mmol), NaHCO3 (42.0 mg, 0.5 mmol), and PEG-400 (2 g) beforestandard cycles evacuation and backfilling with dry and pure carbon monoxide. Triethylsilane(162.8 μl, 1.0 mmol) was added successively. Then, the mixture was stirred at room temperaturefor the indicated time. At the end of the reaction, the reaction mixture was extracted with diethylether (3 × 10 mL). The organic phases were combined, and the volatile components wereevaporated under reduced pressure. The crude product was purified by column chromatography onsilica gel (petroleum ether / diethyl ether). |
68% | With rhodium(III) chloride trihydrate; hydrogen; triethylamine; triphenylphosphine In N,N-dimethyl acetamide at 90℃; for 12h; Autoclave; | General procedure for reductive carbonylation of aryl iodides with CO and H2 General procedure: All reactions were carried out in an 80 mL Teflon-lined stainless steel reactor equipped with a magnetic stirring bar. Typically, in a glovebox, the aryl iodides (1.0 mmol), RhI3(0.025 mmol), PPh3 (0.1 mmol), Et3N (1.2 mmol), and DMA (2 mL) were loaded into the reactor. Then, the autoclave was screwed up, charged with CO and H2 to a total pressure of 10 bar (1:1) and transferred to an oil bath preheated at 90 °C, which was controlled by a Haake-D3 temperature controller. After completion of the reaction, the reactor was cooled in iced water and the gas carefully vented. The conversion and yield of the aryl iodides and arylaldehydes were determined by GC analysis using dodecane as an internal standard. For yield determination of the other products, the reaction mixture was first analyzed by GC-MS to determine the structures of the aromatic aldehyde products. Then, CH2Cl2 (5 mL) was added to the reaction mixture, after which deionized water (10 mL) was added to extract the solvent DMA for 5 times. The organic layer was dried over anhydrous Na2SO4, concentrated by rotary evaporation and finally purified by column chromatography on silica gel using n-hexane/ethyl acetate as eluent to obtain the pure products and isolated yields. |
82 % Chromat. | With 1,4-diaza-bicyclo[2.2.2]octane; palladium diacetate; formic acid In N,N-dimethyl-formamide at 50℃; for 5h; Electrolysis; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With 2-(2-methyl-1-oxopropane)cyclohexanone; caesium carbonate In N,N-dimethyl-formamide at 20℃; for 17h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With 2-(2-methyl-1-oxopropane)cyclohexanone; caesium carbonate In N,N-dimethyl-formamide at 20℃; for 19h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: C10H11IO2 With TurboGrignard In tetrahydrofuran at -20℃; for 2h; Stage #2: 3-thienyl iodide In tetrahydrofuran; toluene at -20℃; for 9h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With ammonium hydroxide; copper(l) iodide; N,N'-bis(3,5-dimethoxyphenyl)cyclopentane-1,1-dicarboxamide; caesium carbonate; In dimethyl sulfoxide; at 20℃; for 24h;Inert atmosphere; Sealed tube; | General procedure: A 10 mL flask was charged with a magnetic stir bar, CuI (19 mg,10 mol%), L2 (86 mg, 20 mol%), Cs2CO3 (651 mg, 2 mmol) and solid aryl iodides (1.0 mmol). The tube was evacuated and backfilled with argon (this procedure was repeated three times). Under a counter flow of Argon, DMSO (1.0 mL), 1.0 mmol aryl iodides (if liquid), 0.9 mL (12.0 mmol) aqueous ammonia (28%) were added by syringe slowly. The reaction mixture was allowed to stir under argon at room temperature for 24 h. Then the mixture was diluted with 30 ml dichloromethane and passed through a fritted glass filter, the filter cake being further washed with 15 ml dichloromethane, dried over Na2SO4, filtered and the most solvent was removed under vacuum. The residue was purified by column chromatography on silica gel with an eluent of petroleum ether and ethyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 2-Picolinic acid; potassium phosphate; copper(l) iodide In dimethyl sulfoxide at 80℃; for 24h; Inert atmosphere; | |
70% | With copper(l) iodide; potassium carbonate; 1,1,3,3-tetramethyl-1,3-bis(3-pyridinyl)disiloxane In N,N-dimethyl-formamide at 100℃; for 24h; Inert atmosphere; | General procedure for preparation of diaryl ether General procedure: Aryl iodide or bromides (1 mmol), ArOH (1 mmol), CuI(20 mol%), and dimethyl di (2-pyridyl)silane (20 mol%) were placed in a small round-bottom flask. DMF (3 mL) and K2CO3(276 mg, 2 mmol) were then added together. The mixture was stirred for 24 h at 100°C in nitrogen atmosphere. The reaction mixture was cooled to room temperature. Ethyl acetate(10 mL) and H2O (1 mL) were added and the mixture was stirred. The organic layer was separated and the aqueous layer was extracted twice more with ethyl acetate (10 mL). Combined organic layer was dried overNa2SO4 and filtered. The filtrate was concentrated and the resulting residue was purified by silica gelchromatography and afforded the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With manganese powder In ethanol for 2h; Reflux; Green chemistry; | |
90% | With triethylamine In N,N-dimethyl-formamide at 80℃; for 3h; | |
89% | With diethylzinc(II); tris(para-trifluoromethyl)phenyl phosphine In tetrahydrofuran; toluene at 110℃; for 24h; |
88% | With potassium carbonate In methanol at 80℃; for 6h; Inert atmosphere; Green chemistry; | General experimental procedures for Sonogashira reaction General procedure: Stirring the mixture of aryl halide (1.00 mmol), phenylacetylene derivative (1.50 mmol), Pd(at)MOF-808 (3 mol %), K2CO3 (2.00 mmol) and methanol (5.00 mL) at 80 °C for 2-8 h. After cooling down the mixture to room temperature, evaporating the solution under reduced pressure. After that, purifying the residue by silica gel column chromatography to collect the target coupling products. |
87% | With 2-aminophenyl diphenylphosphinite; tetrabutylammonium bromide; palladium diacetate; sodium hydroxide In lithium hydroxide monohydrate at 25℃; for 14h; | |
86% | With iron(II,III) oxide; potassium carbonate In ethylene glycol at 125℃; for 20h; | |
84% | With triethylamine; palladium (II) chloride at 20℃; for 2h; Inert atmosphere; Ionic liquid; Sonication; | |
62% | With piperidine In N,N-dimethyl-formamide at 130℃; for 3h; Sealed tube; | |
54% | With [Cu(N,N'-di-methylethylenediamine)2]Cl2·H2O; Cs2CO3; N<SUB>1</SUB>,N<SUB>2</SUB>-dimethylethane-1,2-diamine In 1,4-dioxane; methanol at 135℃; for 22h; Inert atmosphere; | |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In N,N-dimethyl-formamide at 25℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate In ethanol at 80℃; for 12h; Inert atmosphere; | |
99% | With potassium carbonate In water at 90℃; for 12h; | |
99% | With potassium carbonate In ethanol at 80℃; for 5h; Inert atmosphere; | Typical Experimental Procedure of Suzuki-Miyaura Coupling (Table 2, entry1) General procedure: A mixture of 1a (102 mg, 0.5 mmol), phenylboronic acid 2a(91.4 mg, 0.75 mmol), and K2CO3(138 mg, 1.0 mmol) in EtOH (3 mL) was heated in the presence of SGlPd at 80°C for 3 h under argon an atmosphere without stirring. After the reaction mixture was cooled to room temperature, the SGlPd was removed from the reaction mixture and rinsed several time with EtOH. The raction mixture was poured into 2 MNaOH aq., extracted with AcOEt. The organic layer was washed with sat. aq. NH4Cl, and sat. aq. NaCl, dried over anhydrous NaSO4. Concentration at reduced pressure gave yellowish oil, which was chromatographed on silica gel with hexane as the eluent to give the biphenyl (3a, 77.1 mg, 99%) as a colorless solid. The recovered SGlPd catalyst was again subjected to next reaction for second run. The procedure was repeated a total 10 runs. |
96% | With potassium carbonate In water; acetone at 60℃; for 5h; | |
95% | With C72H48Cl3F9P3Pd3S3(1+)*F6Sb(1-); potassium carbonate In water; acetonitrile at 80℃; for 6h; Inert atmosphere; | |
92% | With potassium carbonate In methanol at 40℃; for 3h; | Typical procedure for SMC reaction a definite amount ofpalladium catalyst (1) and base were placed in a dried 25mLround bottom flask, aromatic halide (1.0mmol), phenylboronicacid (1.5mmol) and solvent (6.0mL) were added, andthe mixture was stirred at 40°C for a desired time. Afterthat, the reaction mixture was quenched with water andextracted with ethyl acetate. The combined organic layerswere dried over anhydrous Na2SO4.Solvent was removedunder a reduced pressure and the crude product was purified by silica gel chromatography with a mixture of petroleumether and ethyl acetate. |
99 %Chromat. | With sodium carbonate In water; ethyl acetate; isopropyl alcohol at 50℃; for 0.00138889h; Microchannel flow reactor; | |
95 %Chromat. | With potassium carbonate In water at 80℃; for 3h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium-t-butoxide; C38H58N2O8 at 120℃; for 24h; Sealed tube; Inert atmosphere; | |
87% | With 9,9′-(ethane-1,2-diylbis(azanediyl))bis(1Hphenalen-1-one); potassium-t-butoxide In neat (no solvent) at 130℃; for 12h; Sealed tube; | |
86% | With C70H100N10O10; potassium-t-butoxide at 120℃; for 24h; Schlenk technique; Sealed tube; Inert atmosphere; |
85% | With N,N'-diethylurea; potassium-t-butoxide at 120℃; for 24h; Schlenk technique; Sealed tube; Inert atmosphere; | 2. General procedure for the arylation of arenes General procedure: Aryl iodides (0.2 mmol) t-BuOK (0.6 mmol, 3.0 equiv), and U6 (0.02 mmol, 10 mol%) were added in dried Schlenk tubes. Benzene (2 mL) were added into tubes by syringe. The septum-sealed tube was evacuated and refilled with nitrogen three times. The mixture was stirred under a nitrogen atmosphere in sealed Schlenk tubes at 120 °C for 24 h. The reaction was cooled down to room temperature. The mixture was filtered through a short plug of silica gel, washed with a copious amount of ethyl acetate. The combined organic phase was concentrated under vacuum. The product was purified through flash column chromatography on 300-400 mesh silica gel with hexane/ethyl acetate as eluent. Solvent was removed under vacuum to give the pure product. |
85% | With N,N'-diethylurea; potassium-t-butoxide at 130℃; for 24h; | 11 Example 11: (1) Combine 10mol% diethylurea (0.02mmol), 0.6mmol potassium tert-butoxide, 0.2mmol 3-iodothiopheneAnd 2ml of benzene in the reaction tube, heating and stirring the reaction, the heating and stirring temperature is 130°C , the reaction time is 24h.(2) After the reaction, it is separated by column chromatography (the column packing is 300-400 mesh column chromatography silica gel, eluentIs: petroleum ether), the product 3-phenylthiophene can be obtained with a yield of 85%. |
81% | With quinoline-1-amino-2-carboxylic acid; potassium-t-butoxide at 120℃; for 24h; Sealed tube; Inert atmosphere; | |
81% | With di-tert-butyl hyponitrite; potassium-t-butoxide In dimethyl sulfoxide at 60℃; for 8h; Schlenk technique; Inert atmosphere; | Coupling Reaction of Arenes with Aryl Iodides (Tables 1-2): Representative Procedure(Table 1, Entry 2) General procedure: To a mixture of 4-iodoanisole (1a: 46.8 mg, 0.200 mmol), potassiumtert-butoxide (44.9 mg, 0.400 mmol) and di-tert-butyl hyponitrite (7.0 mg, 0.040 mmol) in a 20mL Schlenk tube was added benzene (2a: 2.1 mL, 24 mmol) and dimethyl sulfoxide (0.14 mL,2.0 mmol), and the resulting mixture was stirred at 60 C for 8 h. The reaction mixture wasquenched with a saturated NH4Cl aqueous solution (2.0 mL) and extracted with ethyl acetate (10mL x 3). Nonane was added as an internal standard for GC analysis, and an aliquot of theorganic layer was subjected to GC analysis. The combined organic layer was dried over MgSO4,filtered, and concentrated in vacuo. The residue was subjected to silica gel chromatography(hexane, PTLC) to give 4-methoxybiphenyl (3aa: 29.8 mg, 81% yield). |
71% | With potassium-t-butoxide; toluene-4-sulfonic acid hydrazide at 110℃; for 24h; Schlenk technique; Inert atmosphere; Sealed tube; | |
69% | With bathophenanthroline; sodium tertiary butoxide at 155℃; for 6h; Inert atmosphere; | |
69% | With potassium-t-butoxide; <i>L</i>-proline at 150℃; for 24h; Sealed tube; Inert atmosphere; | |
68% | With potassium-t-butoxide; phenylhydrazine at 100℃; for 30h; Inert atmosphere; Schlenk technique; | |
67% | With 6-oxo-1,6-dihydropyridine-2-carboxylic acid dimethylamide; potassium-t-butoxide at 25℃; for 24h; Inert atmosphere; UV-irradiation; Green chemistry; | |
64% | With (2-(methylamino)phenyl)methanol; potassium-t-butoxide at 100℃; for 24h; Sealed tube; | |
63% | With ethyl 5-(5-(tert-butoxycarbonylamino)-1-octyl-4-oxo-1,4-dihydropyridine-3-carboxamido)-1-octyl-4-oxo-1,4-dihydropyridine-3-carboxylate; potassium-t-butoxide at 120℃; for 24h; Schlenk technique; Sealed tube; Inert atmosphere; | |
68 %Chromat. | With di-tert-butyl peroxide; potassium-t-butoxide at 85℃; for 24h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: 2-iodo-5-bromopyridine With zinc In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: 3-thienyl iodide With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; chemoselective reaction; | General procedure for Pd-catalyzed coupling reactions (1a - 1g, 2a - 2b) General procedure: In a 50 mL round-bottomed flask, Pd[P(Ph)3]4 (0.06g, 1 mol %) was placed. Next, 16 mL of 0.5 M solution of 5-bromo-2-pyridylzinc iodide (I) in THF was added into the flask. Iodobenzene (0.82g, 4 mmol) was added via a syringe. The resulting mixture was stirred at room temperature overnight. Quenched with saturated NH4Cl solution, then extracted with ethyl acetate (30 mL x 3). Combined organics were washed with saturated Na2S2O3 solution and brine. Dried over anhydrous MgSO4. A flash column chromatography (1 % EtOAc/ 99 % Heptane) gave 0.88g of 1a as a white solid in 941% isolated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N-Bromosuccinimide In N,N-dimethyl-formamide for 1h; | |
87.3% | With N-Bromosuccinimide In N,N-dimethyl-formamide for 1.5h; Inert atmosphere; Heating; | |
75% | With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃; for 12h; Darkness; |
74% | With N-Bromosuccinimide; acetic acid at 100℃; for 1h; Inert atmosphere; | |
74% | With N-Bromosuccinimide; acetic acid at 100℃; for 1h; Inert atmosphere; | |
72% | With N-Bromosuccinimide In N,N-dimethyl-formamide at 50℃; for 17.5h; Cooling with ice; Inert atmosphere; Darkness; | 1 EXAMPLE 1 Synthesis of 2-bromo-3-iodothiophene (1). A solution of 3-iodothiophene (1.10 g, 5.20 mmol) in anhydrous DMF (27 mL) was cooled in an ice bath under N2 and NBS (0.98 g, 5.5 mmol) was added in a single portion. The reaction was protected from light, stirred for 16 h and then heated to 50° C. for 1.5 h. After cooling to room temperature the solution was poured into hexanes (100 mL) and washed with brine (3×100 mL). The organic layer was dried over MgSO4, concentrated, and purified by column chromatography using hexanes as eluent to yield 1.08 g (72%) colorless liquid. 1H NMR (400 MHz, CDCl3) δ 7.22 (d, 2H), 6.94 (d, 2H). |
44% | With N-Bromosuccinimide; acetic acid for 0.5h; Reflux; | |
With N-Bromosuccinimide In N,N-dimethyl-formamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere; | 5.6 (6) A dried round bottom flask was charged with copperCD iodide (0.10 g, 0.53 mmol), cesium carbonate (3.58 g, 11 mmol). The flask was evacuated and backfilled with nitrogen. Under the flow of nitrogen, ( |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With caesium carbonate; thiourea In dimethyl sulfoxide at 110℃; for 18h; Inert atmosphere; chemoselective reaction; | |
79% | With caesium carbonate; thiourea; copper(II) oxide In dimethyl sulfoxide at 20 - 110℃; Inert atmosphere; | 13 General procedure for the synthesis of aryl sulfides: General procedure: To a stirred solution of aryl halides (2.0 mmol) and thiourea (1.2 equiv) in dry DMSO (2.0 mL) at rt was added nano CuO (5.0 mol %) followed by Cs2CO3 (2.0 equiv) and heated at 110 °C for 15 h. The progress of the reaction was monitored by TLC. After the reaction was complete, the reaction mixture was allowed to cool, and a 1:1 mixture of ethyl acetate/water (20 mL) was added. The combined organic extracts were dried with anhydrous Na2SO4. The solvent and volatiles were completely removed under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 9:1) to afford the corresponding coupling product in excellent yields.Recycling of the catalyst:after the reaction was complete, the reaction mixture was allowed to cool, and a 1:1 mixture of ethyl acetate/water (2.0 mL) was added and CuO was removed by centrifugation. After each cycle, the catalyst was recovered by simple centrifugation, washing with deionized water and ethyl acetate and then drying in vacuo. The recovered nano CuO was used directly in the next cycle.Data of representative examples:Dip-tolylsulfane (Table 3, entry 3): yellow oil;1H NMR (200 MHz, CDCl3, TMS): δ = 7.21 (d, 4H, J = 8.0 Hz), 7.06 (d, 4H, J = 8.0 Hz), 2.32 (s, 6H); 13C NMR (50 MHz, CDCl3, TMS): δ = 136.7, 132.81, 131.0, 129.8, 96.1.Table 3, entry 3): yellow oil;1H NMR (200 MHz, CDCl3, TMS): δ = 7.21 (d, 4H, J = 8.0 Hz), 7.06 (d, 4H, J = 8.0 Hz), 2.32 (s, 6H); 13C NMR (50 MHz, CDCl3, TMS): δ = 136.7, 132.81, 131.0, 129.8, 96.1.Bis(4-ethylphenyl)sulfane (Table 3, entry 4): colorless oil; 1HNMR (300 MHz, CDCl3, TMS): δ = 7.21(d, 4H, J = 7.8 Hz), 7.07 (d, 4H, J = 7.8 Hz), 2.62-2.52 (m, 4H), 1.26 (t, 6H, J = 7.8 Hz);13C NMR (75 MHz, CDCl3, TMS): δ = 143.1, 132.7, 131.0, 128.6, 28.3, 15.4; mass (EI): m/z 242 [M]+; Anal. calcd for: (C16H18S) C, 79.29; H, 7.49; S, 13.23; found: C,79.22; H,7.42; S,13.19.Table 3, entry 4): colorless oil; 1HNMR (300 MHz, CDCl3, TMS): δ = 7.21(d, 4H, J = 7.8 Hz), 7.07 (d, 4H, J = 7.8 Hz), 2.62-2.52 (m, 4H), 1.26 (t, 6H, J = 7.8 Hz);13C NMR (75 MHz, CDCl3, TMS): δ = 143.1, 132.7, 131.0, 128.6, 28.3, 15.4; mass (EI): m/z 242 [M]+; Anal. calcd for: (C16H18S) C, 79.29; H, 7.49; S, 13.23; found: C,79.22; H,7.42; S,13.19.Bis(3-nitrophenyl)sulfane (Table 3, entry 7): pale yellow oil; 1H NMR (300 MHz, CDCl3, TMS): δ = 8.19-8.15 (m, 4H), 7.65 (d, 2H, J = 8.3 Hz), 7.55 (t, 2H, J = 8.3 Hz); 13C NMR (75 MHz, CDCl3, TMS): δ = 148.8, 136.7, 130.7, 125.6, 122.7; mass (EI): m/z 276 [M]+; Anal. calcd for: (C12H8N2O4S) C, 52.17; H, 2.92; S, 11.61; N, 10.14; found: C, 52.12; H, 2.86; S, 11.55; N, 10.9.Table 3, entry 7): pale yellow oil; 1H NMR (300 MHz, CDCl3, TMS): δ = 8.19-8.15 (m, 4H), 7.65 (d, 2H, J = 8.3 Hz), 7.55 (t, 2H, J = 8.3 Hz); 13C NMR (75 MHz, CDCl3, TMS): δ = 148.8, 136.7, 130.7, 125.6, 122.7; mass (EI): m/z 276 [M]+; Anal. calcd for: (C12H8N2O4S) C, 52.17; H, 2.92; S, 11.61; N, 10.14; found: C, 52.12; H, 2.86; S, 11.55; N, 10.9.4,4'-Thiodianiline (Table 3, entry 11): brown solid; mp 104-105 °C; 1H NMR (300 MHz, CDCl3, TMS): δ = 7.10 (d, 4H, J = 8.68 Hz), 6.52 (d, 4H, J = 8.68 Hz), 3.51 (br s, 4H); 13C NMR (75 MHz, CDCl3, TMS): δ = 145.5, 133.8, 132.6, 124.8, 115.6; mass (EI): m/z 216 [M]+; Anal. calcd for: (C12H12N2S) C, 66.63; H, 5.59; N, 12.95; S, 14.82; Found: C, 66.61; H, 5.58; N, 12.92; S, 14.81.Table 3, entry 11): brown solid; mp 104-105 °C; 1H NMR (300 MHz, CDCl3, TMS): δ = 7.10 (d, 4H, J = 8.68 Hz), 6.52 (d, 4H, J = 8.68 Hz), 3.51 (br s, 4H); 13C NMR (75 MHz, CDCl3, TMS): δ = 145.5, 133.8, 132.6, 124.8, 115.6; mass (EI): m/z 216 [M]+; Anal. calcd for: (C12H12N2S) C, 66.63; H, 5.59; N, 12.95; S, 14.82; Found: C, 66.61; H, 5.58; N, 12.92; S, 14.81.Dithiophen-3-ylsulfane (Table 3, entry 15): yellow oil; 1H NMR (300 MHz, CDCl3, TMS): δ = 7.31-7.25 (m, 2H), 7.17-7.11(m, 2H), 6.96-6.94 (m, 2H); 13C NMR (75 MHz, CDCl3, TMS): δ = 129.6, 126.4, 124.7; mass (EI): m/z 197 [M]+; Anal. calcd for: (C8H6S3) C, 48.45; H, 3.05; S, 48.50; found: C,48.42; H,3.02; S,48.47.Table 3, entry 15): yellow oil; 1H NMR (300 MHz, CDCl3, TMS): δ = 7.31-7.25 (m, 2H), 7.17-7.11(m, 2H), 6.96-6.94 (m, 2H); 13C NMR (75 MHz, CDCl3, TMS): δ = 129.6, 126.4, 124.7; mass (EI): m/z 197 [M]+; Anal. calcd for: (C8H6S3) C, 48.45; H, 3.05; S, 48.50; found: C,48.42; H,3.02; S,48.47.Dipyrimidin-5-ylsulfane (Table 3, entry 17): colorless oil; 1H NMR (300 MHz, CDCl3, TMS): δ = 9.15 (s, 2H), 8.74(s, 4H); 13C NMR (75 MHz, CDCl3, TMS): δ = 158.6, 157.7, 129.8; mass (EI): m/z 190 [M]+; Anal. calcd for: (C8H6N4S) C, 50.51; H, 3.18; N, 29.45; S, 16.86; found: C, 50.45; H, 3.13; N, 29.41; S, 16.81.Table 3, entry 17): colorless oil; 1H NMR (300 MHz, CDCl3, TMS): δ = 9.15 (s, 2H), 8.74(s, 4H); 13C NMR (75 MHz, CDCl3, TMS): δ = 158.6, 157.7, 129.8; mass (EI): m/z 190 [M]+; Anal. calcd for: (C8H6N4S) C, 50.51; H, 3.18; N, 29.45; S, 16.86; found: C, 50.45; H, 3.13; N, 29.41; S, 16.81. |
74% | With thiourea; potassium hydroxide In water for 24h; Reflux; |
62% | With potassium thioacyanate; copper(II) oxide; potassium hydroxide In dimethyl sulfoxide at 130℃; for 20h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With N-Bromosuccinimide In ethyl acetate at 60℃; for 30h; Inert atmosphere; Sealed tube; | 3.3. 2,5-dibromo-3-iodothiophene (4) 3.3.2. Method B In a 100 mL reactor, purged with argon for 10 min, thecompound 3 (5.00 g, mmol, 1 eq.) and NBS (12.74 g, mmol, 3eq.) were introduced and the reactor was closed with a rubberstopper and was purged with argon for 10 min. Ethyl acetate(70 mL) was added and the reactor was introduced in an oilbath warmed at 60°C and was left to react for 30 h. The reactionwas cooled to rt and the solution was extracted withhexane and washed with water (2 × 50 mL) and brine(1 × 50 mL). The organic phase was collected, dried withsodium sulfate, filtered and evaporated, obtaining a reddishoil. The crude was purified by flash chromatography on BiotageKP Sil 100 g silica column, eluting with hexane. Thecollected fractions were evaporated giving a faint pink oil:8.54 g (98%). The same reaction was also performed at 25°Cfor 5 days, giving nearly the same yield. The NMR spectraare in agreement with the literature [12].1H NMR (200 MHz, CDCl3) δ 6.92 (s, 1H). 13C NMR (50MHz, CDCl3) δ 137.17 (C-4), 116.41 (C-2), 113.55 (C-5),85.28 (C-3). MS (EI, m/z): 365.80. Elemental analysis: requiredfor C4HBr2IS, C 13.06, H 0.27, S 8.72, found: C13.12, H 0.31, S 8.69. |
With N-Bromosuccinimide In N,N-dimethyl-formamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With manganese(II) fluoride; (S,S)-1,2-diaminocyclohexane; caesium carbonate In water at 130℃; for 24h; | |
70% | With copper(l) iodide; manganese(II) fluoride; (1R,2R)-1,2-diaminocyclohexane; potassium hydroxide In water at 100℃; for 48h; | General procedure for N-arylation of nitrogen nucleophiles General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999% purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98% purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With copper(l) iodide; manganese(II) fluoride; (1R,2R)-1,2-diaminocyclohexane; potassium hydroxide In water at 100℃; for 48h; | General procedure for N-arylation of nitrogen nucleophiles General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999% purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98% purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis. |
79% | With manganese(II) fluoride; (S,S)-1,2-diaminocyclohexane; caesium carbonate In water at 130℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With caesium carbonate; copper(II) oxide In dimethyl sulfoxide at 80℃; for 8h; | Representative experimental procedure for the synthesis of N-substituted indoles: General procedure: To a stirred solution of aryl halides (1.0 mmol) and indoline/indoline carboxylic acid (1.0 equiv) in dry DMSO (2.0 mL) at rt was added nano CuO (5.0 mol %) followed by Cs2CO3 (2.0 equiv) and heated at 80 °C for 8 h. The progress of the reaction was monitored by TLC. After the reaction was complete, the reaction mixture was cooled to room temperature and catalyst was filtered, the crude residue was extracted 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 (7:3) as eluent to give the corresponding N-substituted indoles in excellent yields. The identity and purity of the product were confirmed by 1H, 13C NMR, and mass spectra. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 3-ethynylthiophene With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 60℃; Inert atmosphere; Stage #2: 3-thienyl iodide at 60℃; for 16h; Inert atmosphere; | |
90% | Inert atmosphere; | |
89% | With copper(I) oxide; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 135℃; for 8h; Inert atmosphere; Sealed tube; |
73% | With palladium diacetate; sodium hydroxide In water; acetone at 60℃; for 18h; | |
With copper(l) iodide; [PdCl2(triphenylphosphine)]2; triethylamine In N,N-dimethyl-formamide at 80℃; for 10h; Inert atmosphere; Sealed tube; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Schlenk technique; Inert atmosphere; | Synthesis of substrates 1,2-diphenylethyne derivatives General procedure: Chapter one: A 100 mL schlenk tube was charged with iodobenzene (3.0 mmol), ethynyltrimethylsilane (3.6 mmol), PdCl2(PPh3)2 (0.15 mmol), CuI (0.15 mmol), Et3N:THF = 3:2 (10.0 mL). Then the tube was charged with nitrogen, and was stirred at room temperature for the indicated time until complete consumption of starting material as monitored by TLC analysis. After the completion of the reaction, then the reaction mxtuire was filtered and the filtrate diluted in ethyl acetate and washed with water. The combined organic layers were dried over anhydrous Na2SO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography (petroleum ether unless otherwise noted) to give the corresponding trimethyl(phenylethynyl)silanes, and used for the next reaction. | |
With copper(l) iodide; sym,trans-[PdCl2(PPh3)2]; triethylamine at 20℃; for 10h; Inert atmosphere; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With ammonium hydroxide; 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phosphaadamantane; palladium diacetate In toluene at 100℃; for 20h; Autoclave; | General procedure for Palladium-Catalyzed Aminocarbonylation of Aryl Iodides Using Aqueous Ammonia: General procedure: To a 45 mL glass-lined autoclave, 1 (0.5 mmol), Pd(OAc)2 (0.01mmol), CYTOP292 (0.02mmol), aqueous ammonia (0.2 mL) and toluene (10 mL) were sequentially added. After sealing, the autoclave was purged three times with carbon monoxide and pressurized with 100 psi of CO. The resulting mixture was then heated at 100 °C for 20 h. The autoclave was removed from the oil bath and cooled to room temperature prior to the release of excess carbon monoxide. The reaction mixture was concentrated by rotary evaporator, and purified by flash chromatography on silica gel with a mixture of hexanes and ethyl acetate (2:1to 1:2) as the eluent to afford the products. |
86% | With 1,4-diaza-bicyclo[2.2.2]octane; N-methoxylamine hydrochloride; sodium iodide; palladium dichloride In acetonitrile at 90℃; for 8h; Autoclave; Inert atmosphere; | Aminocarbonylation of Aryl and Heteroaryl Iodides;General Procedure General procedure: To an autoclave (100 mL capacity), were added an arylhalide (1 mmol), methoxylamine hydrochloride (1.2 equiv),DABCO (2 equiv), PdCl2 (10 mol%), NaI (0.2 mmol) and MeCN (15 mL), under an inert atm. The autoclave was flushed three times with CO and then pressurized to 5 atm of CO. The mixture was stirred with a mechanical stirrer (550rpm) at 90 °C for 8 h. The reactor was cooled to r.t., degassed carefully, opened and the reaction mixture removed. The reactor vessel was washed with EtOAc (2 × 5 mL) to remove residual product. The mixture was filtered and the filtrate washed with brine (2 × 4 mL), dried over Na2SO4, filtered and the solvent evaporated under vacuum. Purification of the residue was carried out by column chromatography (silicagel, 100-200 mesh, PE-EtOAc) to afford the corresponding product in good to excellent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In dimethyl sulfoxide at 70℃; for 8h; | 15 4.2.15 3-Benzyl-5-(1-(3-thienyl)vinyl)-2-oxazolidinone (2ao) General procedure: The reaction of Pd(PPh3)4 (17 mg, 0.015 mmol), K2CO3 (85 mg, 0.62 mmol), 1a (48 mg, 0.30 mmol), 3-iodothiophene (78 mg, 0.37 mmol), and a balloon of carbon dioxide (about 1 L) in 2 mL of DMSO afforded 81 mg of 2ao (94%) as an oil (petroleum ether/ethyl acetate=4:1): 1H NMR (300 MHz, CDCl3) δ 7.36-7.18 (m, 6H, ArH), 7.00-6.93 (m, 1H, H in thienyl), 6.90 (d, J=3.6 Hz, 1H, H in thienyl), 5.54 (s, 1H, one proton of C=CH2), 5.42 (s, 1H, one proton of C=CH2), 5.32 (t, J=8.0 Hz, 1H, OCH), 4.49 (d, J=15.0 Hz, 1H, one proton of CH2 in Bn), 4.35 (d, J=14.7 Hz, 1H, one proton of CH2 in Bn), 3.67 (t, J=9.0 Hz, 1H, one proton of NCH2 in oxazolidinone ring), 3.19 (t, J=7.7 Hz, 1H, one proton of NCH2 in oxazolidinone ring); 13C NMR (75 MHz, CDCl3) δ 157.4, 139.5, 138.7, 135.3, 128.7, 127.91, 127.87, 127.5, 125.3, 124.0, 112.5, 73.2, 49.4, 48.1; MS (m/z) 285 (M+, 3.48), 241 (M+-CO2, 54.57), 91 (100); IR (neat, cm-1) ν 2951, 2919, 2850, 1748, 1621, 1430, 1374, 1325, 1248, 1190, 1012; HRMS calcd for C16H15NO2S (M+): 285.0824, found 285.0823. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With palladium diacetate; triethylamine In N,N-dimethyl-formamide at 80℃; for 24h; | 5 Synthesis of (E)-1-(3-thiopheno)parthenolide (PNR-5-53) A mixture of parthenolide (50 mg, 0.20 mmol), triethylamine (60 mg, 0.61 mmol), and 3-iodothiophene (46 mg, 0.21 mmol) in DMF (0.1 ml) was treated with palladium(ll) acetate (0.5 mg, 0.002 mmol) and then heated at 80°C under air. After 24 h, the reaction mixture was allowed to cool to room temperature, water (8 mL) was added, and the resultant mixture was extracted with ethyl acetate (10 ml x 3). The separated organics were dried over Na2SO4 and concentrated under reduced pressure. The obtained crude residue was purified by using silica flash chromatography (hexanes/EtOAc; 9:1-4:1) to afford the (E)-13-(3-thiopheno)parthenolide as a white solid (35 mg) in 52 % yield. MP 183-185°C; 1H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 2.8 Hz, 1 H), 7.51 (s, 1 H), 7.41 (s, 1 H), 7.20-7.21 (d, J= 4.4 Hz, 1 H), 5.28-5.31 (d, J =12 Hz, 1 H), 3.96-4.00 (t, J=6.8Hz, 1 H), 3.18 (m, 1 H), 2.82-2.84 (d, J=8.8 Hz, 1 H), 2.43 (m, 1 H), 2.16-2.30 (m, 5H), 1.72 (s, 3H), 1.54 (m, 1 H), 1.33 (s, 3H), 1.26-1.31 (m, 1 H); 13C NMR (100 MHz,CDCl3) δ 171.09, 135.37, 134.52, 131.85, 129.28, 127.78, 127.33, 126.49, 125.42, 82.7, 66.41, 61.64, 46.92, 42.10, 35.99, 30.56, 24.36, 17.52, 17.30 ppm. |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-ethyl-N,N-diisopropylamine In toluene at 80℃; | 5.1.1 General synthetic procedure for C-C bond formation (5a-h) General procedure: A mixture of parthenolide (1.0mmol) and an appropriate aromatic iodide (1.1mmol) was refluxed at 80°C using palladium (II) ferrocene (0.01mmol) and di-isopropylethyl-amine (3.0mmol) in toluene (0.1ml) under air for 18-24h. The reaction mixture was then allowed to cool to room temperature, water (8ml) added, and the resultant mixture was extracted with ethyl acetate (10ml×3). The separated organics were dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The obtained crude residue was purified by silica flash chromatography (9:1 to 4:1, hexanes/EtOAc) to afford the corresponding aryl substituted parthenolide as a solid (40-50mg) in 70-80% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: 3-thienyl iodide With water; cesium fluoride In dimethyl sulfoxide at 20℃; for 0.166667h; Stage #2: tert-butylisonitrile In dimethyl sulfoxide at 90℃; for 9h; | Benzamides 3; General Procedure General procedure: A mixture of aryl halide (1.0 mmol), CsF (1.0 mmol), PS-Pd-NHC (1 mol%), and DMSO-H2O (9:1) (2 mL) were added successively to a 10-mL round-bottom flask. The mixture stirred at r.t. for 10 min. Then isocyanide (1.2 mmol) was added and the mixture was stirred with a magnetic stirrer at 90 °C for 9 h. The mixture was filtered to separate the catalyst and the filtrate was extracted with EtOAc (3 × 5 mL). The combined organic layers were dried (anhyd Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether-EtOAc, 10:1) to give the final pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With [ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; potassium carbonate; triphenylphosphine; In benzene; at 150℃; for 24h;Sealed tube; | General procedure: In a 30-mL sealed tube, <strong>[2622-63-1]1-methyl-2-phenylbenzimidazole</strong> (1, 0.25mmol), [RuCl2(p-cymene)]2 (0.0125 mmol), Ph3P (0.075 mmol),K2CO3 (0.50 mmol), and iodoarene (0.25 mmol) were combined inanhydrous benzene (2 mL) under air. The mixture was then stirredat 150 °C for 24 h. The mixture was cooled to r.t., diluted with EtOAc, and filtered through a small pad of Celite. The filtrate was concentrated in vacuo and purified by flash chromatography (silicagel, EtOAc?hexane) to give the analytically pure 2-(biphenyl-2-yl)benzimidazoles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With water; palladium diacetate; potassium carbonate at 20℃; for 12h; | 4-Nitrobenzoic Acid (2a) General procedure: A 25-mL flask was charged with Pd(OAc)2 (1.2 mg, 0.005 mmol), 1-iodo-4-nitrobenzene (1a, 127.0 mg, 0.5 mmol), K2CO3 (141.0 mg, 1.0 mmol), H2O (0.5 mL), and PEG 400 (2.0 mL); the flask was subjected to standard cycles (3 ×) of evacuation and back-filling with dry and pure CO. The mixture was stirred at r.t. for the indicated time. The mixture was poured into sat. aq NaCl (15 mL), acidified to pH 3 with 3 M aq HCl, and extracted with EtOAc (3 × 15 mL). The solvent was removed from the combined organic phases on a rotary evaporator. The crude product was purified by column chromatography (silica gel, PE-EtOAc-HCO2H, 25:1:1) to afford 2a as a light yellow solid; yield: 75mg (90%); mp 238.0-239.3 °C. 1H NMR (400 MHz, DMSO-d6): δ = 13.68 (br s, 1 H), 8.30 (d, J = 8.0 Hz,2 H), 8.14 (d, J = 8.0 Hz, 2 H). 13C NMR (100 MHz, DMSO-d6): δ = 165.9, 150.0, 136.4, 130.7, 123.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With copper(l) iodide; potassium <i>tert</i>-butylate; N<SUP>1</SUP>,N<SUP>2</SUP>-bis(pyridin-2-ylmethyl)oxalamide In dimethyl sulfoxide at 20℃; for 24h; Inert atmosphere; Sealed tube; Schlenk technique; | |
50% | With cobalt(II) oxalate dihydrate; caesium carbonate; N,N`-dimethylethylenediamine In water at 120℃; for 24h; Green chemistry; | General Procedure for N-Arylation of Pyrrolidinone/AliphaticAmides: General procedure: A mixture of cobalt(II) oxalate dihydrate(Sigma-Aldrich, 0.294 mmol), Cs2CO3 (2.94 mmol), pyrrolidinoneor aliphatic amide (1.47 mmol), DMEDA (0.588 mmol),distilled H2O (0.3 mL) and aryl halide (2.205 mmol) were addedto an 8.0-mL reaction vial fitted with a Teflon-sealed screw cap.The reaction mixture was stirred under air in a closed system at120 °C and 130 °C, respectively for 24 h. The heterogeneousmixture was subsequently cooled to r.t. and diluted withCH2Cl2. The combined organic extracts were dried over anhydNa2SO4, filtered and the solvent was removed under reducedpressure. The crude product was loaded into the column usingminimal amounts of CH2Cl2 and was purified by silica gel column chromatography to afford the N-arylated product. Theidentity and purity of products were confirmed by 1H NMR and13C NMR spectroscopic analysis. |
With potassium phosphate In dimethyl sulfoxide at 110℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With selenium; potassium phosphate; copper(l) chloride In dimethyl sulfoxide at 140℃; for 24h; Inert atmosphere; Schlenk technique; | |
67.9% | With selenium; potassium phosphate; copper(l) chloride In dimethyl sulfoxide at 20 - 120℃; for 27h; Inert atmosphere; | 6 Example 6: At room temperature, the reaction vessel in an organic solvent DMSO was added the above formula (II) compound, the compound of formula (III), elemental Se, CuCl and K3PO4.Wherein the molar ratio of the compound of formula (II) and the formula (III) is 1: 2, compound with elemental Se molar ratio of formula (II) is 1: 3 molar amount of CuCl is of formula (II) compound molar amount 20 %, with a compound of formula (II) K3PO4The molar ratio of 1: 1.5, and then purged with nitrogen, and replaced twice, in a nitrogen atmosphere such that the reaction environment; was warmed to 120 deg.] C, and the reaction incubated for 27 hours.After post-treatment to give the product of formula (the I), in a yield of 67.9%, purity 98.1% (HPLC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium phosphate; copper; In dimethyl sulfoxide; at 100℃; for 24h; | General procedure: A mixture of Cu0 powder (Sigma-Aldrich, <425mum, 99.5% trace metals basis, 0.095mg, 0.015mmol, 3-mol%), anhydrous K3PO4 (0.75mmol), <strong>[872-35-5]2-mercaptoimidazole</strong>/sulfur-containing azoles (0.5mmol), DMSO (0.2mL) and aryl halide (0.75mmol) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 100C for 24h. The heterogeneous mixture was subsequently cooled to room temperature and diluted with 4.0mL dichloromethane. The combined organic extracts were dried with anhydrous Na2SO4, filtered and the solvent was removed under reduced pressure. The crude product was loaded onto the column using minimal amounts of dichloromethane and was purified by silica-gel column chromatography to afford the S-arylated product. The identity and purity of products was confirmed by 1H and 13C NMR spectroscopic analys. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 3-thienyl iodide; methyl 2-methyl-2-(phenylsulfonylamido)propionic acid With sodium acetate; palladium diacetate In acetonitrile at 100℃; for 12h; Stage #2: With copper(l) iodide In acetonitrile at 20 - 100℃; for 8h; | 4.1.1. General procedure for palladium(II)/copper(I)-catalyzed sequential C-H arylation and oxidative C-N bond cleavage of arylsulfonamino acids General procedure: A mixture of aryl sulfonamide 1 (0.25 mmol), aryl iodide 2 (0.5 mmol), Pd(OAc)2 (0.025 mmol), NaOAc (0.5 mmol), and CH3CN (0.5 mL) was placed in a 25 mL Schlenk tube with a rubber plug. The tube was heated at 100 oC for 12h. At this point, the reaction mixture was cooled to room temperature, and the CuI (0.025 mmol) was added. The reaction mixture was reheated to 100 °C for an additional 8h, and the product was extracted with EtOAc (3×5 mL). Combined organic layers were dried over Na2SO4, concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/EtOAc = 5/1) to afford the desired product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium phosphate; copper(l) iodide; N′,N′-diphenyl-1H-pyrrole-2-carbohydrazide In diethylene glycol at 100℃; for 12h; Sealed tube; | 16 Synthesis of N-phenyl 3-thienylamine The 210 mg (1mmol) 3 - iodo thiophene, 121 mg (1.3mmol) aniline, 9.5 mg (0.05mmol) CuI, 15 mg (0.05mmol) ligand L1, 424mg (2mmol) K3PO4, 2 ml DEG, adding 10 ml reaction tube, sealing, 100 °C reaction under the condition 12h. After the stop of the reaction, water, extracted with ethyl acetate, washing, saturated salt water washing, after drying with anhydrous sodium sulfate, filtered, the filtrate is distilled under reduced pressure, purification by silica gel chromatography separation column column, shall be N - phenyl 3 - thiophenine 158 mg, yield 90%. |
86% | With potassium phosphate; copper(l) iodide; N′,N′-diphenyl-1H-pyrrole-2-carbohydrazide In diethylene glycol at 20℃; Sealed tube; | |
53% | With (1,2-dimethoxyethane)dichloronickel(II); Ir[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]2(4,4'-di-tert-butyl-2,2'-bipyridyl)PF6; triethylamine; 4,4'-di-tert-butyl-2,2'-bipyridine In acetonitrile at 23 - 25℃; for 24h; Sealed tube; Irradiation; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With cesiumhydroxide monohydrate; sodium carbonate; sodium iodide; iron(II) chloride; In chloroform; at 120℃; for 12h; | Compound 11:A 25 mL reaction flask was charged with ferrous chloride (0.05 mmol),4-iodothiophene (0.5 mmol),4-ethoxycarbonylphenylboronic acid (0.75 mmol),Sodium carbonate (1.Ommol),Cesium hydroxide monohydrate (2.5 mmol),Sodium iodide (0.251111] 100),(0.75_31),Chloroform (1.5_31) and polyethylene glycol-400 (2. (^),And reacted at 120 for 12 h. Cooled to room temperature,extraction,The solvent was evaporated under reduced pressure and the residue was isolated by column chromatography to obtain 88% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With copper(l) iodide; ethylenediamine; sodium t-butanolate; In toluene; at 100℃; for 4.0h; | General procedure: CuI (10mol%) and EDA (10mol%) were added to a mixtureof O-alkyl carbamate (1mmol), NaOtBu (1.5mmol) and aryl halide (1mmol) in 2mL toluene and the mixture wasstirred for the appropriate time, which was determined byTLC monitoring, at 100C. After completion of the reaction,the catalyst was removed by filtration and 20mL H2Owas added to the filtrate. The resultant mixture was extractedwith CHCl3.Then the organic phase was washed with water(2 × 10mL) and dried over anhydrous Na2SO4.After evaporationof CHCl3under reduced pressure, the correspondingcrude product was purified by flash chromatography to givethe desired pure cross-coupling product in good to excellentyield. In the case of using arylboronic acids as couplingpartners, Cu(OAc)2 was employed instead of CuI. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tris-(dibenzylideneacetone)dipalladium(0); trifuran-2-yl-phosphane; potassium carbonate; In acetonitrile; at 80℃; under 375.038 Torr; for 24.0h;Schlenk technique; | General procedure: Aryl iodide (1 mmol), nucleophile (0.8-1.2 mmol), tris-(2-furyl)-phosphine (TFP) (10 mol %), tris-dibenzylideneacetonedipalladium (0) (Pd2dba3) (2.5 mol %), base (2 mmol) and MeCN (20 mL) were combined in a Schlenk tube. After two freeze-pump-thaw cycles, allene gas (0.5 atm) was charged into the Schlenk tube, the mixture thawed and then heated for 16-24 h at 70-80C with magnetic stirring. After cooling to room temperature and venting excess allene, DCM (10 mL) was added, the mixture filtered, and the filtrate evaporated in vacuo. Column chromatography of the residue afforded the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | Stage #1: 4,6-dichloropyrimidine With bis(2,2,6,6-tetramethylpiperidinyl)zinc, lithium chloride, magnesium chloride complex In tetrahydrofuran at 0 - 20℃; for 2h; Stage #2: 3-thienyl iodide With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 20 - 65℃; for 16.3333h; | 1 4,6-Dichloro-5-(thiofen-3-yl)pyrimidine (3) 4,6-Dichloropyrimidine (2) was zincated according to modified literature procedure (Mosrin, M.;Knochel, Chem. Eur. J. 2009, 15, 1468-1477). 4,6-Dichloropyrimidine (2) (950 mg, 6.30 mmol)was dissolved in THF (10 ml) and added dropwise into an ice-cooled solution of(TMP)2Zn.MgC12.LiC1 in THF (0.35 M, 9.0 ml, 3.15 mmol) and the reaction mixture was stirred at0 °C for 1 hour, then let to warm to r.t. for one hour and added to a solution of 3-iodothiophene(0.74 ml, 6.7 mmol) and Pd(PPh3)4 (775 mg, 0.67 mmol) in THF (3 ml), which was pre-stirred atr.t. for 20 mm., and stirred at 65 ° for 16 hrs. Solvent was evaporated under reduced pressure andcrude mixture was purified by HPFC (hexane/EtOAc 0 - 1%) to give 3 (890 mg, 58 %) as a white solid. m.p. 178 - 180 °C. JR (ATR): v = 2932, 2862, 1510, 1404, 1326, 813, 774. ‘H NMR (600.1 MHz, CDC13): 7.15 (dd, 1H, J4,5 = 4.9, J4,2 = 1.4, H-4-thienyl); 7.47 (dd, 1H, J2,5 = 3.0, J2,4 = 1.4, H-2-thienyl); 7.48 (dd, 1H, J5,4 = 4.9, i_s,2 = 3.0, H-5-thienyl); 8.75 (s, 1H, H-2). ‘3C NMR (150.9MHz, CDC13): 126.12 (CH-5-thienyl); 126.91 (CH-2-thienyl); 128.08 (CH-4-thienyl); 129.83 (C-5); 131.56 (C-3-thienyl); 156.44 (CH-2); 161.55 (C-4,6). APCJ MS mlz (rel%): 231 (100) [M+H]. HR MS (APCJ) for C8H5N2C125 [M+H]: calcd 230.95450; found 230.95456 |
890 mg | Stage #1: 4,6-dichloropyrimidine With bis(2,2,6,6-tetramethylpiperidinyl)zinc, lithium chloride, magnesium chloride complex In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: 3-thienyl iodide With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 65℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.5% | With sulfuryl dichloride; diphenyl sulfide; antimony(III) chloride In 1,2-dichloro-ethane at 20 - 25℃; for 4h; | 10 [Example 10] 1 g of 3-iodothiophene (4.76 mmol; manufactured by Tokyo Chemical Industry Co., Ltd.)0.02 g (0.095 mmol; antimony chloride) (manufactured by Wako Pure Chemical Industries, Ltd.) and 0.018 g (0.095 mmol, diphenyl sulfide manufactured by Wako Pure Chemical Industries, Ltd.) of antimony chloride were dissolved in 5 g of ethylene dichloride,Subsequently, 0.83 g (6.19 mmol; manufactured by Wako Pure Chemical Industries, Ltd.) of sulfuryl chloride was added,The reaction was carried out at 20 to 25 ° C. for 4 hours. After completion of the reaction,A 10 wt% hydrochloric acid aqueous solution was addedWell, after stirring for a while,The organic layer was separated. Then,Neutralized with a 10 wt% aqueous sodium hydroxide solution,The organic layer was separated.Purity of the target product and content of by-products in the obtained reaction solution were analyzed by GC.2-chloro-4-iodothiophene: 83.54%, haloSubstitution (byproduct): 0.00%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With copper(l) iodide; ethylenediamine; sodium t-butanolate In toluene at 100℃; for 5.5h; | 2.2 General Procedure for the Synthesis of Alkyl Aryl Carbamates General procedure: CuI (10mol%) and EDA (10mol%) were added to a mixtureof O-alkyl carbamate (1mmol), NaOtBu (1.5mmol) and aryl halide (1mmol) in 2mL toluene and the mixture wasstirred for the appropriate time, which was determined byTLC monitoring, at 100°C. After completion of the reaction,the catalyst was removed by filtration and 20mL H2Owas added to the filtrate. The resultant mixture was extractedwith CHCl3.Then the organic phase was washed with water(2 × 10mL) and dried over anhydrous Na2SO4.After evaporationof CHCl3under reduced pressure, the correspondingcrude product was purified by flash chromatography to givethe desired pure cross-coupling product in good to excellentyield. In the case of using arylboronic acids as couplingpartners, Cu(OAc)2 was employed instead of CuI. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium phosphate; palladium dichloride; In water; N,N-dimethyl-formamide; at 20℃; for 4h; | General procedure: tert-Butyl nitrite (155 mg, 1.1 mmol) was added drop wise to a mixture ofbis(pinacolato)diborane (127 mg, 0.5 mmol), 4-anisidine (61 mg, 0.5 mmol)and eosin Y (0.01 mmol) in acetonitrile (3 mL). The resulting mixture wasstirred at room temperature under irradiation with blue LED for 2 h (TLC).Acetonitrile was then evaporated and DMF-water (1:1, 4 mL) was addedfollowed by PdCl 2 (3 mg, 5 mol %), K 3 PO 4 (138 mg, 0.65 mmol) and 1-iodo-2-methylbenzene (131 mg, 0.6 mmol), respectively. The reaction mixture wasstirred for 4 h at room temperature (TLC) and was extracted with ethyl acetate(3 10 mL). The extract was washed with water (5 mL) and brine (5 mL) anddried over Na 2 SO 4 . The crude product was puried by column chromatographyover silica gel (hexane) to afford pure 4-methoxy-2-methyl-1,10-biphenyl as ayellow viscous liquid (172 mg, 87%).1H NMR (500 MHz, CDCl 3 ) d 2.39 (s, 3H),3.94 (s, 3H), 7.05-7.08 (m, 2H), 7.33-7.38 (m, 6H);13C NMR (125 MHz, CDCl 3 ) d20.6, 55.3, 113.6 (2C), 125.8, 127.1, 129.9, 130.3(2C), 130.4, 134.5, 135.5, 141.7,158.6. These data are in perfect match with those reported for an authenticsample.17cThis procedure was followed for all the reactions listed in Table 3.All of these products (4a,17a4b,17b4c,17c4d,17d4e,17a4f,17e4g,17f4h,17g) areknown compounds, and their spectroscopic data are in agreement with thosepreviously reported. Although these experiments were performed with0.5 mmol scale similar results were obtained in higher (10-15 mmol) scale. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With dichloro bis(acetonitrile) palladium(II); sodium acetate In water at 100℃; for 12h; Green chemistry; | S3 General procedure for the Heck-arylation/cyclisation of ortho-hydroxy cinnamate esters General procedure: o-hydroxy-cinnamate ester 1 (0.5 mmol,), aryl iodides 2 (1.0 mmol, 2.0 equiv), Pd(OAc)2 (0.05 mmol, 10 mol %), and H2O (1ml) was charged into a pressure tube. The reaction mixture was stirred at 100 °C for 12 h under air. After cooled to room temperature, the reaction mixture was diluted with EtOAc (5 mL) and washed with NH4Cl (3 x 5 mL). The organic phase was separated, dried over NaSO4 and the solvent was removed in vacuo. The residue was purified by column chromatography by using hexanes/ethyl acetate as eluent to afford the desired products 3a-z. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium fluoride; copper (I) iodide In dimethyl sulfoxide at 60℃; for 15h; Inert atmosphere; Schlenk technique; | 9 Preparation of Heteroaryldifluoroacetic Acid Ester Compound 2,2-Difluoro-2- (thiophen-3-yl) acetic acid ethyl ester (Compound 3h) was prepared according to the following procedure.In the Schlenk tube,3 - Iodothiophene (105.2 mg, 0.5 mmol), copper (I) iodide (190.5 mg, 1.0 mmol), potassium fluoride (58.1 mg, 1.0 mmol) and DMSO (2.0 mL). Finally, α- (trimethylsilyl) difluoroacetic acid ethyl ester (Compound 2a) (196.3 mg, 1.0 mmol) was added and the mixture was stirred at 60 ° C. for 15 hours under a nitrogen atmosphere. After the reaction, trifluoroethanol (50.0 mg, 0.5 mmol) was added as an internal standard and measurement by 19 F-NMR revealed that 2,2-difluoro-2- (thiophene-3-yl) acetic acid ethyl ester (compound 3 h) was produced in a yield of 77%. The reaction mixture was extracted with ethyl acetate, washed with water and dried over anhydrous sodium sulfate. Anhydrous sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. Purification of the residue by silica gel column chromatography (Hexane: EtOAc = 50: 1) gave 2,2-difluoro-2- (thiophene-3-yl) acetic acid ethyl ester (Compound 3h) (76.5 mg, 0.37 mmol, Yield: 74%). |
With potassium fluoride; copper (I) iodide In dimethyl sulfoxide at 60℃; for 15h; Inert atmosphere; | A Step A: E-1 (6.42 g, 30.57 mmol) was added to dimethyl sulfoxide (50 mL) followed by potassium fluoride (3.55 g, 61.14 mmol) and cuprous iodide (11.64 g, 61.14 mmol) and finally ethyl (trimethylsilyl)difluoroacetate (12 g, 61.14 mmol) was added. The reaction mixture was stirred at 60 degrees Celsius for 15 hours under nitrogen protection. After natural cooling, tert-butyl methyl ether (200 mL) and water (300 mL) were added to dilute the reaction solution, and stirring was continued for 10 minutes, followed by filtration. The filter cake was washed with tert-butyl methyl ether (30 mL/time, washed 3 times). The filtrates were combined, and the organic phase was separated, washed with water (300 mL) and saturated brine (300 mL) in turn, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent: petroleum ether) to obtain E-2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With sodium azide; copper(ll) sulfate pentahydrate; sodium carbonate; sodium L-ascorbate; <i>L</i>-proline In water; dimethyl sulfoxide at 70℃; Inert atmosphere; | 3.3.5. 2,8-Bis((1-(thiophen-3-yl)-1H-1,2,3-triazol-4-yl)methoxy)quinoline, 2b General procedure: A mixture of an aromatic or benzylic halide (1 mmol), quinoline-propargyl compound (for 1a-1c 1 mmol andfor 2a-2c and 3a-3c 0.5 mmol), L-proline (24 mg, 0.2 mmol), Na2 CO3 (24 mg, 0.2 mmol), NaN3 (65 mg, 1mmol), sodium ascorbate (20 mg, 0.1 mmol), DMSO/H2 O (18:2, 2.0 mL), and CuSO4 5H2 O solution (1 M,0.05 mL) in a 20-mL scintillation vial was stirred overnight at 70 C. The crude mixture was poured into colddilute NH4 OH solution (30 mL) and extracted with ethyl acetate (4 20 mL). The collected organic layer waswashed with brine, dried over MgSO4 , and concentrated in vacuo. The crude product was purified by flashcolumn chromatography using mixtures of ethyl acetate and hexane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With bis-triphenylphosphine-palladium(II) chloride; formic acid; triethylamine; tris-(o-tolyl)phosphine In dimethyl sulfoxide at 70℃; for 24h; | 1. Typical reaction procedure General procedure: PdCl2(PPh3)2 (0.1 mmol), P(o-tolyl)3 (0.1 mmol), TFben(0.5 mmol) and indole (1.0 mmol) were transferred into an ovendriedtube (15 mL), which was evacuated and backfilled withN2(5x). DMSO (2 mL), aryl iodide (1.2 mmol), Et3N (1 mmol) andHCO2H (1.5 mmol) were added into the tube via syringe. The reactionmixture was stirred at 70 °C for 24 h. After the reaction wascomplete, the mixture was filtrated and extracted with DCM. Thecombined organic layers were washed with H2O and brine, driedover anhydrous Na2SO4, and then concentrated under vacuum.The crude product was purified by column chromatography on silicagel (petroleum ether/ethyl acetate = 20/1) to afford the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | Stage #1: Methyl isobutyrate With 2,2,6,6-tetramethylpiperidinyl-lithium In toluene at 20℃; for 0.25h; Glovebox; Stage #2: 3-thienyl iodide With di-μ-iodobis(tri-t-butylphosphino)dipalladium(l) In toluene at 20℃; Glovebox; chemoselective reaction; | General procedure for the dinuclear Pd(I)-mediated enolate arylation General procedure: Inside the glovebox, lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 70.7 mg, 0.48 mmol, 1.2 eq.) was dissolved in toluene (1.5 mL) and carbonyl compound (3, 0.48 mmol, 1.2 eq.) was added. After 15 min of stirring at ambient temperature a solution of Pd(I) iodo dimer (2, 3.5 mg, 0.004 mmol, 1 mol% for aryl iodides; 17.4 mg, 0.02 mmol, 5 mol% for aryl bromides) and aryl halide (4, X = I or Br, 0.4 mmol, 1.0 eq.) in toluene (0.5 mL) was added. After 4-18 h of further stirring at ambient temperature (reaction progress was monitored by GCMS), the crude was directly adsorbed onto silica (washing with diethyl ether) and purified by flash column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With magnesium In N,N-dimethyl-formamide at 110℃; for 20h; Inert atmosphere; Schlenk technique; Green chemistry; | Heterogeneous copper(I)-catalysed C-Se coupling reaction; general procedure General procedure: Under an argon atmosphere, a Schlenk tube was charged with bpy-MCM-41-CuI (78 mg, 0.05 mmol), diaryl diselenide (0.25 mmol), aryl iodide (0.5 mmol), Mg turnings (24 mg, 1.0 mmol) and DMF (1.5 mL). The mixture was stirred at 110 °C under Ar for 20-40 h. After completion of the reaction, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (15 mL), and filtered. The bpy-MCM-41-CuI catalyst residue was washed with 1.0 M dilute hydrochloric acid (2 × 5 mL), water (2 × 5 mL), and acetone (2 × 5 mL) when being reused in another catalytic cycle. The filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography on silica gel (petroleum ether (60-90 °C)/ethyl acetate) to provide the desired product 3. CAUTION: All reactions using selenium containing compounds should be carried out in a well-ventilated fume cupboard. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 30℃; Schlenk technique; Inert atmosphere; | 6 (1) Specifically, 1 mmol of Compound V-1, 0.05 mmol of copper (I) iodide, 0.03 mmol of Bis(triphenylphosphine)palladium(II) dichloride, 20 mL of tetrahydrofuran (THF), 2 mL of triethylamine and 1.2 mmol of Compound IV-1 were added sequentially to a 50 mL Schlenk tube under nitrogen atmosphere. The mixture was stirred at 30° C. until TLC analysis confirmed complete conversion of the raw materials. Thereafter, the mixture was filtered, spin-dried, dry-loaded onto a column, and separated using column chromatography, thereby obtaining 126 mg of yellow solid, that is, Compound III-1, with a yield of 51%. |
49% | Stage #1: 2-methyl-3-(prop-2-yn-1-yloxy)-4H-pyran-4-one With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In tetrahydrofuran for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: 3-thienyl iodide With triethylamine In tetrahydrofuran at 20℃; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With selenium; oxygen; copper diacetate; sodium carbonate In 1-methyl-pyrrolidin-2-one at 120℃; for 18h; Schlenk technique; Green chemistry; | |
82% | With selenium; oxygen; copper diacetate; sodium carbonate In 1-methyl-pyrrolidin-2-one at 120℃; for 18h; | 9 Synthesis of 1-methyl-3-morpholinyl-4-(3-thienyl)maleimide compound At room temperature, 3-iodothiophene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv) , Copper acetate (0.02mmol, 0.1equiv), sodium carbonate (0.8mmol, 4equiv) and 1mL N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, stirring at 120 reaction temperature for 18h . The reaction mixture was cooled, then ethyl acetate was added for dilution, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and combined To the organic phase, add 5g of anhydrous sodium sulfate, stand still for 30 minutes, wash the filter cake 3 times with 5mL ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether = 8 :1), the product is a yellow liquid, the yield is 82%, and the product weight is 59 mg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.08% | Stage #1: 3-thienyl iodide With n-butyllithium; diisopropylamine In diethyl ether at -78℃; for 1h; Stage #2: 3-(tert-butyldimethylsilanyloxy)propionaldehyde In diethyl ether for 1h; | 11C 3-((tert-butyldimethylsilyl)oxy)-1-(3-iodothiophen-2-yl)propan-1-ol n-BuLi (2.5 M, 20.95 mL) was added dropwise into a solution of diisopropylamine (5.3 g, 52.37 mmol) in diethyl ether (100 mL) at -78°C, and the reaction mixture was warmed up to 0°C with stirring for 30 min. Then, 3-thiophene (10 g, 47.61 mmol) was added to the reaction solution at -78°C and stirred for 1h. Example 11B was added dropwise to the above reaction solution, followed by stirring for another 1 hour. The reaction solution was quenched with saturated ammonium chloride solution (100 mL) and extracted with ethyl acetate (50 mL * 4). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography to give the title compound as yellow oil (15 g, 79.08%). 1H NMR (400MHz, CHLOROFORM-d) δ= 7.24 (d, J=5.3 Hz, 1H), 7.02 (d, J=5.3 Hz, 1H), 5.19 (td, J=2.8, 8.5 Hz, 1H), 4.32 (d, J=2.5 Hz, 1H), 3.94 (dd, J=4.6, 6.1 Hz, 2H), 2.04 - 1.93 (m, 2H), 0.94 (s, 9H), 0.12 (d, J=1.3 Hz, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.89% | A solution of N-butyllithium (2.5 mol/L, 10.46 mL) in n-hexane was slowly added dropwise in a solution of diisopropylamine (2.65 g, 26.16 mmol, 3.68 mL) in diethyl ether (40 mL) at -78C over about 10 min, during wihch the temperature was controlled at -78C. After completion of dropwise addition, the mixture was warmed up to 0C and stirred for 30 min. The reaction system was then cooled down to -78C, and added with 3-iodothiophene (5.49 g, 26.16 mmol). After stirring for 30 min, <strong>[2987-17-9]cyclobutylcarboxaldehyde</strong> (2 g, 23.78 mmol) was added dropwise, and stirred at -78C for 2 h. The system was added with 50 mL of saturated ammonium chloride solution, and then extracted with ethyl acetate (50 mL * 3). The organic phase was combined and washed with 50 mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate, filtered under suction and evaporated under reduced pressure. The crude compound obtained was purified by column chromatography to give the compound of cyclobutyl-(3-iodo-2-thienyl)methanol as a colorless liquid (3 g, 10.20 mmol, yield of 42.89%). 1H NMR (400MHz, CHLOROFORM-d) delta = 7.26 - 7.23 (m, 1H), 7.01 (d, J=5.3 Hz, 1H), 4.94 (d, J=7.8 Hz, 1H), 2.84 - 2.71 (m, 1H), 2.15 - 2.07 (m, 3H), 1.91 - 1.87 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With Iron(III) nitrate nonahydrate; potassium phosphate; copper(II) oxide In N,N-dimethyl-formamide at 90℃; Inert atmosphere; | 2. Synthesis of Substrates 3a-3v. General procedure: In a round bottom flask, tert-butanesulfinamide (152 mg, 1.26 mmol), 1-chloro-4-iodobenzene (200 mg, 0.84 mmol), Fe(NO3)3•9H2O (51 mg, 0.13 mmol), K3PO4 (354 mg, 1.68 mmol), CuO (6.7 mg, 0.084 mmol) mixed with fresh distillated DMF (0.9 mL) in a nitrogen atmosphere. The mixture was kept stirring at 90 oC overnight until the substrate was completely consumed (monitored by TLC analysis). Then, H2O (10 mL) was added, and the mixture was extracted by ethyl acetate (3 x 10 mL). The combined organic phase was dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether: ethyl acetate = 2:1) to furnish the desired compound 3a (180 mg, 93 % yield) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With Wilkinson?s catalyst; 1,3-bis-(diphenylphosphino)propane; water; In tetrahydrofuran; at 140℃; for 12h;Inert atmosphere; Sealed tube; | General procedure: Rh(PPh3)3Cl (2.5 mol%) and DPPP (0.04 mmol) were transferred into an oven-dried tube(15 mL), which was evacuated and backfilled with N2 (5x). THF(2 mL), H2O (1 mmol), aryl iodides (1.2 mmol), furfural (1 mmol)and amine (1.8 mmol) were added into the tube via syringe and sealed with Teflon plug. The reaction mixture was stirred at 140 C for 12 h. After the reaction was complete, the mixture was concentrated by rotary evaporation. The crude product was purified by column chromatography (EA/PE = 1/20) on a silica gel to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine In tetrahydrofuran at 40℃; for 8h; Schlenk technique; Inert atmosphere; Sealed tube; enantioselective reaction; | (R)-3-(3-(Difluoromethyl)-5-phenylpent-1-yn-1-yl)thiophene (6c). To a 25 mL of Schlenk was addedPdCl2(PPh3)3 (7.0 mg, 0.01 mmol, 0.05 equiv) and CuI (3.8 mg, 0.02 mmol, 0.1 equiv). The mixture wasevacuated and backfilled with argon for three times. Compound 5d (39 mg, 0.2 mmol, 1.0 equiv), 3-iodothiophene (54.6 mg, 0.26 mmol, 1.3 equiv), iPr2NH (202 mg, 2.0 mmol, 10.0 equiv) and THF (2 mL) wereadded. The Schlenk tube was sealed with a screw-cap and put into a 40 oC oil bath. After stirring for 8 h, thereaction mixture was cooled to room temperature and concentrated. The residue was purified by flash columnchromatography on silica gel (n-hexane/AcOEt = 80/1) to give compound 6c (45 mg, 82% yield) as a colorlessoil. [α]D20 = 60.6 (c = 1.400, CHCl3) for a sample with 95:5 er; 1H NMR (400 MHz, CDCl3) δ 7.46 (dd, J = 2.9,1.0 Hz, 1H), 7.33 - 7.18 (m, 6H), 7.13 (dd, J = 5.0, 1.1 Hz, 1H), 5.79 (td, J = 56.4, 4.2 Hz, 1H), 3.04 - 2.92 (m, 2H), 2.84 - 2.73 (m, 1H), 2.09 - 1.88 (m, 2H). 19F NMR (376 MHz, CDCl3) δ -119.00 (ddd, J = 275.1, 56.3,12.4 Hz, 1F), -121.31 (ddd, J = 275.2, 56.5, 13.8 Hz, 1F). 13C NMR (101 MHz, CDCl3) δ 140.7, 123.0, 129.0,128.6, 128.52, 128.47, 126.2, 125.2, 115.7 (t, J = 245.5 Hz), 83.8 (t, J = 7.1 Hz), 80.1, 37.1 (t, J = 23.0 Hz),32.8, 29.5 (t, J = 3.0 Hz). IR (thin film) max 2959, 1384, 1131, 1053 cm-1. MS (EI): m/z (%) 276 (M)+, 225, 191(100). HRMS (EI): Calculated for C16H14F2S: 276.0784; Found: 276.0777 (M)+. Enantiomeric purity (er = 95:5)was measured by chiral HPLC on OJH column (i-PrOH:n-hexane = 5:95, 0.7 mL/min, UV detection at 214 nm);tR =22.890 min (major), tR =19.007 min (minor). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With D-galacturonic acid; potassium carbonate; copper(I) bromide In water; dimethyl sulfoxide at 80 - 100℃; Inert atmosphere; Green chemistry; | General Procedure for Catalytic Experiments General procedure: To a 10 mL vial was charged with aryl halide (0.8 mmol), N-containing heterocycle (1.0 mmol), CuBr (0.04 mmol), GalA (0.08mmol), K2CO3 (2.4 mmol), and 50% aq DMSO. The flask wasevacuated and backfilled with argon three times, and the reaction mixture was stirred at appropriate temperature under oil bath for the indicated time. After the complete consumption of aryl halide monitored by TLC, the mixture was then cooled to ambient temperature (if the product was acidic, the mixture was acidified), diluted with ethyl acetate (5 mL), filtered via aCelite pad, and washed with ethyl acetate (10-20 mL). The organic layer was separated by the separating funnel, which was washed successively with water (2 × 10 mL) and brine (2 ×10 mL). The organic layer was dried over anhydrous MgSO4 and concentrated by reduced pressure in a rotary evaporator, which was then purified by column chromatography on silica gel to provide the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With N-ethyl-N,N-diisopropylamine In toluene at 110℃; for 24h; Inert atmosphere; | Heterogeneous Palladium-Catalyzed Carbonylative Synthesis of 2-Arylbenzoxazinones 3; General Procedure General procedure: MCM-41-Pd(OAc)2 (5 mol%), 2-iodoaniline 1 (1.2 mmol) and aryl iodide2 (1.0 mmol) (if solid). The vial was purged with argon and then aryl iodide 2 (1.0 mmol) (if liquid), DiPEA (4.0 mmol), and toluene (2mL) were injected by syringe. The vial was placed in an alloy plate and the plate was then transferred into a 300 mL autoclave under argon. After the autoclave had been flushed with CO (3×), the CO pressure was adjusted to 5 bar and the reaction was carried out for 24 h at 110°C. Upon completion of the reaction, the autoclave was cooled to ambient temperature and the pressure was released cautiously. EtOAc(10 mL) was then added and the resulting mixture was filtered. The Pd catalyst was recovered, by washing with distilled water (2 × 5 mL) and acetone (2 × 5 mL), followed by drying under vacuum at 80 °C for 2 h, and reused in the next cycle. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, light PE-EtOAc, 10:1) to afford the desired product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With N-ethyl-N,N-diisopropylamine In toluene at 110℃; for 24h; Inert atmosphere; | Heterogeneous Palladium-Catalyzed Carbonylative Synthesis of 2-Arylbenzoxazinones 3; General Procedure General procedure: MCM-41-Pd(OAc)2 (5 mol%), 2-iodoaniline 1 (1.2 mmol) and aryl iodide2 (1.0 mmol) (if solid). The vial was purged with argon and then aryl iodide 2 (1.0 mmol) (if liquid), DiPEA (4.0 mmol), and toluene (2mL) were injected by syringe. The vial was placed in an alloy plate and the plate was then transferred into a 300 mL autoclave under argon. After the autoclave had been flushed with CO (3×), the CO pressure was adjusted to 5 bar and the reaction was carried out for 24 h at 110°C. Upon completion of the reaction, the autoclave was cooled to ambient temperature and the pressure was released cautiously. EtOAc(10 mL) was then added and the resulting mixture was filtered. The Pd catalyst was recovered, by washing with distilled water (2 × 5 mL) and acetone (2 × 5 mL), followed by drying under vacuum at 80 °C for 2 h, and reused in the next cycle. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, light PE-EtOAc, 10:1) to afford the desired product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With N-ethyl-N,N-diisopropylamine In toluene at 110℃; for 24h; Inert atmosphere; | Heterogeneous Palladium-Catalyzed Carbonylative Synthesis of 2-Arylbenzoxazinones 3; General Procedure General procedure: MCM-41-Pd(OAc)2 (5 mol%), 2-iodoaniline 1 (1.2 mmol) and aryl iodide2 (1.0 mmol) (if solid). The vial was purged with argon and then aryl iodide 2 (1.0 mmol) (if liquid), DiPEA (4.0 mmol), and toluene (2mL) were injected by syringe. The vial was placed in an alloy plate and the plate was then transferred into a 300 mL autoclave under argon. After the autoclave had been flushed with CO (3×), the CO pressure was adjusted to 5 bar and the reaction was carried out for 24 h at 110°C. Upon completion of the reaction, the autoclave was cooled to ambient temperature and the pressure was released cautiously. EtOAc(10 mL) was then added and the resulting mixture was filtered. The Pd catalyst was recovered, by washing with distilled water (2 × 5 mL) and acetone (2 × 5 mL), followed by drying under vacuum at 80 °C for 2 h, and reused in the next cycle. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, light PE-EtOAc, 10:1) to afford the desired product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With copper(l) iodide; sodium azide; sodium L-ascorbate; N,N`-dimethylethylenediamine In ethanol; water at 50℃; for 20h; | 3 3,5-dichloro-N-(2-(l-(thiophen-3-yl)-lH-l,2,3-triazol-4-yl)propan-2-yl)benzamide (GWL2.190) In a round bottom flask, pronamide (intermediate 1) (122 mg, 0.476 mmol, 1.0 eq.), 3-iodothiophene (100 mg, 0.476 mmol, 1.0 eq.), copper(I)iodide (9 mg, 0.048 mmol, 0.1 eq.), sodium L-ascorbate (10 mg, 0.048 mmol, 0.1 eq.), and sodium azide (62 mg, 0.952 mmol, 2.0 eq.) were dissolved 4.7 ml of 7:3 ethanol to deionized water. Then, N, N’- dimethylethylenediamine (12 mg, 0.01 ml, 0.136 mmol, 0.2 eq.) was added via syringe. The reaction mixture was placed in an oil bath at 50 °C and allowed to mix for 20 hours. The reaction was monitored by TLC with 1 : 1 EtO Ac/Hex. Upon completion, the reaction mixture was diluted with deionized water and extracted three times with ethyl acetate. The organic extracts were combined, washed with brine, and dried over anhydrous sodium sulfate. The crude material was purified by column chromatography with 3 :7 EtO Ac/Hex. The product was a white solid. 86% (157 mg). NMR (400 mHz, DMSO-de, TMS) d 8.71 (s, 1H), 8.59 (s, 1H), 8.00 (dd, J=1.36, 1.80, 1.40, 1H), 7.87 (d, J=1.88, 2H), 7.79 (t, J=1.88, 1H), 7.78 (m, J=2.00, 5.28, 1H), (dd, J=1.36, 5.24, 1.36, 1H) 1.75 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With aluminum (III) chloride; palladium diacetate; triethylamine; triphenylphosphine; lithium chloride In N,N-dimethyl-formamide at 85℃; for 20h; Sealed tube; Inert atmosphere; | 1.2 General procedure General procedure: Pd(OAc)2 (3mol %; 6.7mg), PPh3 (6mol %; 15.7mg), AlCl3 (5mol %; 6.6mg), LiCl (1.5mmol; 63.6mg), and a 2.5mL vial containing TFBen (2.0mmol; 420mg) were added to an oven-dried tube (15mL), which was then placed under vacuum and refilled with nitrogen for three times 9. Aryl iodides (1.2mmol), epoxides (1.0mmol), Et3N (1.5mmol; 209μL), and DMF (2mL) were added into the tube via syringe. The tube was sealed and the mixture was stirred at 85°C in an oil bath for 20h. After the reaction was finished, the crude mixture was filtered and concentrated under vacuum. The crude product was purified by column chromatography on silica gel (PE/EA=100/1) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With 1,2-bis(diphenylphosphino)ethane nickel(II) chloride; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; lithium iodide; zinc In tetrahydrofuran at 100℃; for 12h; Inert atmosphere; | 10 Preparation Example 10 Add 0.3 mmol of diphenyl antimony chloride IX (R1 = n-Bu, R2, R3 = H), 0.3 mmol of 3-iodothiophene (R4 = 3-Thiophene) containing bridged nitrogen atom ligand into a 25 mL reaction tube, 0.03mmol 1,2-bis(diphenylphosphine)ethane nickel chloride, 0.03mmol 1,1'-binaphthalene-2,2'-bisdiphenylphosphine, 0.6mmol zinc powder and 0.6mmol lithium iodide. For vacuum, backfill with nitrogen three times, add 3 mL of tetrahydrofuran (THF) under a nitrogen atmosphere, and react at 100° C. for 12 h. After the reaction is completed, wash with 9 mL 1N dilute hydrochloric acid solution three times (3 mL each time), and then neutralize with saturated sodium bicarbonate solution to pH=7. The organic phase was obtained by liquid separation, which was washed with water, dried, and concentrated under reduced pressure to obtain a crude product. The crude product is separated and purified by column chromatography to obtain a pure compound with a yield of 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethylamine In N,N-dimethyl-formamide at 100℃; for 4h; Green chemistry; | General experimental procedures for Heck reaction General procedure: The reactions were conducted in similar way as for Sonogashira reaction. Stirring the mixture of aryl halide (1.00 mmol), styrene derivative (1.50 mmol), Pd(at)MOF-808 (3 mol %), Et3N (2.00 mmol) and DMF (5.00 mL) at 100 °C for 2-8 h. After cooling down the mixture to room temperature, evaporating the solution under reduced pressure. After that, purifying the residue by silica gel column chromatography to collect the target coupling products |
Tags: 10486-61-0 synthesis path| 10486-61-0 SDS| 10486-61-0 COA| 10486-61-0 purity| 10486-61-0 application| 10486-61-0 NMR| 10486-61-0 COA| 10486-61-0 structure
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H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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