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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
2-Methylbenzaldehyde is an endogenous metabolite.
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Design and synthesis of imidazo[1,2-a]pyridine-chalcone conjugates as antikinetoplastid agents
Agarwal, Devesh S. ; Beteck, Richard M. ; Ilbeigi, Kayhan ; Caljon, Guy ; Legoabe, Lesetja J. ;
Abstract: A library of imidazo[1,2-a]pyridine-appended chalcones were synthesized and characterized using 1H NMR,13C NMR and HRMS. The synthesized analogs were screened for their antikinetoplastid activity against Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Leishmania infantum. The analogs were also tested for their cytotoxicity activity against human lung fibroblasts and primary mouse macrophages. Among all screened derivatives, (E)-N-(4-(3-(2-chlorophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active against T. cruzi and T. b. brucei exhibiting IC50 values of 8.5 and 1.35 μM, resp. Against T. b. rhodesiense, (E)-N-(4-(3-(4-bromophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active with an IC50 value of 1.13 μM. All synthesized active analogs were found to be non-cytotoxic against MRC-5 and PMM with selectivity indexes of up to more than 50.
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Keywords: antikinetoplastid ; chalcone ; drug likeliness properties ; imidazo[1,2-a]pyridine ; neglected tropical diseases (NTDs) ; Trypanosoma brucei brucei ; Trypanosoma brucei rhodesiense
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Selective and Cell-Active PBRM1 Bromodomain Inhibitors Discovered through NMR Fragment Screening
Shifali Shishodia ; Raymundo Nuñez ; Brayden P. Strohmier ; Karina L. Bursch ; Christopher J. Goetz ; Michael D. Olp , et al.
Abstract: PBRM1 is a subunit of the PBAF chromatin remodeling complex that uniquely contains six bromodomains. PBRM1 can operate as a tumor suppressor or tumor promoter. PBRM1 is a tumor promoter in prostate cancer, contributing to migratory and immunosuppressive phenotypes. Selective chemical probes targeting PBRM1 bromodomains are desired to elucidate the association between aberrant PBRM1 chromatin binding and cancer pathogenesis and the contributions of PBRM1 to immunotherapy. Previous PBRM1 inhibitors unselectively bind SMARCA2 and SMARCA4 bromodomains with nanomolar potency. We used our protein-detected NMR screening pipeline to screen 1968 fragments against the second PBRM1 bromodomain, identifying 17 hits with Kd values from 45 μM to >2 mM. Structure–activity relationship studies on the tightest-binding hit resulted in nanomolar inhibitors with selectivity for PBRM1 over SMARCA2 and SMARCA4. These chemical probes inhibit the association of full-length PBRM1 to acetylated histone peptides and selectively inhibit growth of a PBRM1-dependent prostate cancer cell line.
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Purchased from AmBeed: 77326-36-4 ; 104-87-0 ; 2148-56-3 ; 63329-53-3 ; 1591-37-3 ; 387-45-1 ; 936-08-3 ; 1123-56-4 ; 2819989-75-6 ; 703-80-0 ; 1885-29-6 ; 115643-59-9 ; 15764-16-6 ; 487-68-3 ; 145737-61-7 ; 5779-95-3 ; 88-68-6 ; 6575-11-7 ; 77326-62-6 ; 88-65-3 ; 4635-59-0 ; 5779-94-2 ; 56043-01-7 ; 5779-93-1 ; 1591-38-4 ; 446-52-6 ; 62803-47-8 ; 1885-31-0 ; 620-23-5 ; 54166-95-9 ; 22179-72-2 ; 529-20-4 ; 100-52-7 ; 123-11-5 ; 1711-06-4 ; 454-89-7 ; 170875-01-1 ; 883032-29-9 ; 2819989-61-0 ; 1915012-21-3 ; 2819989-58-5 ; 2819989-60-9 ; 2819989-57-4 ; 2819989-68-7 ; 2819989-67-6 ; 111478-13-8 ; 73096-42-1 ; 2835-78-1 ; 118-92-3 ; 22458-07-7 ; 80258-99-7 ; 24782-64-7 ; 1108790-90-4 ; 175204-03-2 ; 97-96-1 ; 780802-33-7 ; 89-98-5
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Nitrothiazole-Thiazolidinone Hybrids: Synthesis and in Vitro Antimicrobial Evaluation
Dylan Hart ; Lesetja J. Legoabe ; Omobolanle J. Jesumoroti ; Audrey Jordaan ; Digby F. Warner ; Rebecca Steventon , et al.
Abstract: Herein we report the synthesis of novel compounds inspired by the antimicrobial activities of nitroazole and thiazolidin-4-one based compounds reported in the literature. Target compounds were investigated in vitro for antitubercular, antibacterial, antifungal, and overt cell toxicity properties. All compounds exhibited potent antitubercular activity. Most compounds exhibited low micromolar activity against S. aureus and C. albicans with no overt cell toxicity against HEK-293 cells nor haemolysis against human red blood cells. Notably, compound 3b exhibited low to sub-micromolar activities against Mtb, MRSA, and C. albicans. 3b showed superior activity (0.25 μg/ml) against MRSA compared to vancomycin (1 μg/ml).
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CAS No. : | 529-20-4 |
Formula : | C8H8O |
M.W : | 120.15 |
SMILES Code : | CC1=C(C=O)C=CC=C1 |
MDL No. : | MFCD00003338 |
InChI Key : | BTFQKIATRPGRBS-UHFFFAOYSA-N |
Pubchem ID : | 10722 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
* 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 |
---|---|---|
87% | With pyridine;Reflux; | To a stirred solution of o-methylbenzaldehyde (50 g, 417 mmol) in pyridine (2 equiv, 65 mL) was added malonic acid (86.6 g, 834 mmol) and the mixture was refluxed for 4-5 h. The reaction mixture was then poured into ice-water followed by 1N HCl. The white solid precipitated out was filtered, washed with water and concentrated under high vacuum for 3-4 h to get the desired product (57 g, 87%). |
87% | With pyridine;Reflux; | lntermediate-1 : o-Methylcinnamic acid: To a stirred solution of o-methylbenzaldehyde (50 g, 417 mmol) in pyridine (2 equiv, 65 ml_) was added malonic acid (86.6 g, 834 mmol) and the mixture was refluxed for 4-5 h. The reaction mixture was then poured into ice-water followed by 1 N HCI. The white solid precipitated out was filtered, washed with water and concentrated under high vacuum for 3-4 h to get the desired product (57 g, 87%). |
55% | With pyridine; In ethanol; for 48h;Reflux; | Briefly, into a 250-mL round-bottom flask, was placed a solution of 2- methylbenzaldehyde (8 g, 66.58 mmol, 1.00 equiv) in ethanol (80 mL), malonic acid (7.6 g, 73.03 mmol, 1.10 equiv), Pyridine (5 mL). The resulting solution was heated to reflux for 48 hr and allowed to cool to room temperature. The crystalline mass which formed was collect by filtration and washed with ethanol. This resulted in 6 g (55%) of (E -3-o- tolylacrylic acid as a white solid. Next, into a 250-mL round-bottom flask was placed a solution of (is)-3-o-tolylacrylic acid (12 g, 73.99 mmol, 1.00 equiv) in methanol (80 mL), Palladium carbon (2 g, 10%). Hydrogen was bubbled into the solution and the resulting solution was stirred overnight at room temperature. The solids were filtered out and the residue was concentrated under vacuum. This resulted in 12 g (98%) of 3-o-tolylpropanoic acid as colorless oil. Next, a solution of 3-o-tolylpropanoic acid (12 g, 73.08 mmol, 1.00 equiv) in TfOH (70 mL) was placed into a 250-mL round-bottom flask. The resulting solution was stirred overnight at room temperature. Then, ice-water was added and extracted with DCM. The combined organic phases were dried over anhydrous Na2S04. After filtration and concentration, the residue was applied onto a silica gel column with EA/PE=1/100 to 1/50. This resulted in 10.6 g (98%) of 4-methyl-2,3-dihydroinden-l-one as a white solid. Next, a solution of l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole (270 mg, 1.36 mmol, 1.00 equiv) in tetrahydrofuran (15 mL) was placed into a 100-mL 3- necked round-bottom flask. This was followed by the addition of n-BuLi (0.55 mL, 2.5M) with dropwise under N2 and stirred for 1 h at -70C. To this was added 4-methyl-2,3- dihydroinden-l-one (200 mg, 1.37 mmol, 1.00 equiv) in tetrahydrofuran (5 mL) dropwise. The reaction mixture was warmed to room temperature over a period of 1 h and the mixture was continued to stir overnight at rt. Then water was added and extracted with EA. The combined organic phases were dried over anhydrous a2S04. After filtration and concentration, the residue was purified by MPLC. This resulted in 250 mg (53%) of 4- methyl- 1 -(1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-imidazol-2-yl)-2,3 -dihydro- 1 H-inden- l-ol as colorless oil. Finally, a solution of 4-methyl-l-(l-((2- (trimethylsilyl)ethoxy)methyl)- 1 H-imidazol-2-yl)-2,3 -dihydro- 1 H-inden- 1 -ol ( 100 mg, 0.29 mmol, 1.00 equiv) in HCOOH (10 mL), Palladium carbon (10 mg) was placed into a 100 mL round bottom flask. The resulting solution was heated to reflux for one overnight. The pH value of the solution was adjusted to 8 with aqueous sodium bicarbonate solution and extracted with EA. The combined organic phases were dried over anhydrous Na2S04. After filtration and concentration, the residue was purified by MPLC. This resulted in 40 mg (67%) of 2-(4-methyl-2,3-dihydro-lH-inden-l-yl)-lH-imidazole as a white solid. LCMS(m/e) 199 (M+H); XH NMR (300 MHz, CDC13) delta ppm 6.96-7.18 (m, 3H), 6.93 (s, 2H), 4.59 (t, J=8.1 Hz, 1H), 2.80-3.00 (m, 2H), 2.50-2.62 (m, 1H), 2.29 (s, 3H), 2.45-2.29 (s, 1H). |
55% | With pyridine; In ethanol; for 48h;Reflux; | Briefly, into a 250-mL round-bottom flask, was placed a solution of 2-methylbenzaldehyde (8 g, 66.58 mmol, 1.00 equiv) in ethanol (80 mL), malonic acid (7.6 g, 73.03 mmol, 1.10 equiv), Pyridine (5 mL). The resulting solution was heated to reflux for 48 hr and allowed to cool to room temperature. The crystalline mass which formed was collect by filtration and washed with ethanol. This resulted in 6 g (55%) of (E)-3-o-tolylacrylic acid as a white solid. Next, into a 250-mL round-bottom flask was placed a solution of (E)-3-o-tolylacrylic acid (12 g, 73.99 mmol, 1.00 equiv) in methanol (80 mL), Palladium carbon (2 g, 10%). Hydrogen was bubbled into the solution and the resulting solution was stirred overnight at room temperature. The solids were filtered out and the residue was concentrated under vacuum. This resulted in 12 g (98%) of 3-o-tolylpropanoic acid as colorless oil. Next, a solution of 3-o-tolylpropanoic acid (12 g, 73.08 mmol, 1.00 equiv) in TfOH (70 mL) was placed into a 250-mL round-bottom flask. The resulting solution was stirred overnight at room temperature. Then, ice-water was added and extracted with DCM. The combined organic phases were dried over anhydrous Na2SO4. After filtration and concentration, the residue was applied onto a silica gel column with EA/PE=1/100 to 1/50. This resulted in 10.6 g (98%) of 4-methyl-2,3-dihydroinden-1-one as a white solid. Next, a solution of 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (270 mg, 1.36 mmol, 1.00 equiv) in tetrahydrofuran (15 mL) was placed into a 100-mL 3-necked round-bottom flask. This was followed by the addition of n-BuLi (0.55 mL, 2.5M) with dropwise under N2 and stirred for 1 h at -70 C. To this was added 4-methyl-2,3-dihydroinden-1-one (200 mg, 1.37 mmol, 1.00 equiv) in tetrahydrofuran (5 mL) dropwise. The reaction mixture was warmed to room temperature over a period of 1 h and the mixture was continued to stir overnight at rt. Then water was added and extracted with EA. The combined organic phases were dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by MPLC. This resulted in 250 mg (53%) of 4-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)-2,3-dihydro-1H-inden-1-ol as colorless oil. Finally, a solution of 4-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)-2,3-dihydro-1H-inden-1-ol (100 mg, 0.29 mmol, 1.00 equiv) in HCOOH (10 mL), Palladium carbon (10 mg) was placed into a 100 mL round bottom flask. The resulting solution was heated to reflux for one overnight. The pH value of the solution was adjusted to 8 with aqueous sodium bicarbonate solution and extracted with EA. The combined organic phases were dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by MPLC. This resulted in 40 mg (67%) of 2-(4-methyl-2,3-dihydro-1H-inden-1-yl)-1H-imidazole as a white solid. LCMS (m/e) 199 (M+H); 1H NMR (300 MHz, CDC3) delta ppm 6.96-7.18 (m, 3H), 6.93 (s, 2H), 4.59 (t, J=8.1 Hz, 1H), 2.80-3.00 (m, 2H), 2.50-2.62 (m, 1H), 2.29 (s, 3H), 2.45-2.29 (s, 1H). |
With piperidine; pyridine; at 85℃; for 24h; | General procedure: A mixture of aromatic aldehydes (3.2 mmol), malonic acid (3.87 mmol), piperidine (0.387 mmol) was dissolved in pyridine and stirred on 85 for 24 h. The pyridine was removed at the vacuum. The reaction mixture was poured into water and washed with HCl. And the precipitate was filtered and washed with hexane for three times, and dried under vacuum to afford the cinnamic acids. | |
With piperidine; pyridine; at 85℃; for 24h; | General procedure: A mixture of aromatic aldehydes (3.2 mmol), malonic acid (3.87 mmol), piperidine (0.387 mmol) was dissolved in pyridine and stirred on 85 C for 24 h. The pyridine was removed at the vacuum. The reaction mixture was poured into water and washed with HCl. And the precipitate was filtered and washed with hexane for three times, and dried under vacuum to afford the cinnamic acids. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With triethylsilane; palladium diacetate; sodium hydrogencarbonate; sodium carbonate; at 20℃; under 760.051 Torr; for 48h; | 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). |
82% | With rhodium(III) chloride trihydrate; hydrogen; triethylamine; triphenylphosphine; In N,N-dimethyl acetamide; at 90℃; under 7500.75 Torr; for 12h;Autoclave; | 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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With potassium tert-butylate; In DMF (N,N-dimethyl-formamide); at 5 - 20℃; for 20h;Product distribution / selectivity; | 4.54 g of tetraethyl 4,4'-dimethylbiphenyl-alpha,alpha'-diyl-diphosphonate and 2.64 g of 2-methylbenzaldehyde were dissolved in 40 ml of N,N-dimethylformamide. At 5 to 10 C., 2.60 g of potassium tert-butoxide was gradually added to the reaction over 10 minutes. Subsequently, the reaction mixture was stirred at room temperature for 20 hours, and then poured into a mixture consisting of 150 ml of water and 150 ml of ethanol. The precipitate was recovered by filtration, washed with water and then dried to obtain pale yellow crystals. The crystals were re-crystallized from a mixed solvent of toluene and ethanol, to obtain 1.88 g of pale yellow crystals (yield 49%). The elementary analysis of this product resulted in 93.09% carbon (theoretical value as compound2-17: 93.22%), and 6.60% hydrogen (theoretical value as compound 2-17: 6.78%). In infrared absorption spectrum (KBr tablet), stretching vibration due to aromatic rings was recognized at around 1600 cm-1. In mass spectrum, a molecular ion peak m/z=386 was recognized. From these results, it was confirmed that the compound thus obtained was compound No.2-17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 223 4-Methoxy-3-(2-methyl-benzylamino)-N-phenyl-benzamide The title compound has been made using the procedure of Example 50, but using 3-amino-4-methoxy-N-phenyl benzamide and 2-methylbenzaldehyde as starting materials, which are commercially available from Aldrich; m.p. 167-169 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With SBA-15/SO3H; In neat (no solvent); at 60℃; for 0.583333h;Green chemistry; | General procedure: In this work SBA-15 nanoreactor was synthesized by the procedure reported by Zhao et al. [6a] and then modified with mercaptopropyltrimethoxysilane (MPTMS) and oxidized to the sulfonic acid [6b] nanoparticle using hydrogen peroxide (Fig. 1). A mixture of diketene (3 mmol), aldehyde (1 mmol), enamine (1 mmol) and alcohol (4 mL) and SBA-15/SO3H (0.07 g, ~4 mol%) was reacted under neat conditions for appropriate time (TLC). After that, 20 mL hot EtOH was added to the reaction vessel and, with simple centrifuging, the catalyst was removed as filtrate, washed and then the product recrystallized from hot ethanol. All of the products are synthesized by four-component method and were identified by their physical and spectral data (mp, IR, 1H NMR and 13C NMR). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With SBA-15/SO3H; In neat (no solvent); at 60℃; for 0.416667h;Green chemistry; | General procedure: In this work SBA-15 nanoreactor was synthesized by the procedure reported by Zhao et al. [6a] and then modified with mercaptopropyltrimethoxysilane (MPTMS) and oxidized to the sulfonic acid [6b] nanoparticle using hydrogen peroxide (Fig. 1). A mixture of diketene (3 mmol), aldehyde (1 mmol), enamine (1 mmol) and alcohol (4 mL) and SBA-15/SO3H (0.07 g, ~4 mol%) was reacted under neat conditions for appropriate time (TLC). After that, 20 mL hot EtOH was added to the reaction vessel and, with simple centrifuging, the catalyst was removed as filtrate, washed and then the product recrystallized from hot ethanol. All of the products are synthesized by four-component method and were identified by their physical and spectral data (mp, IR, 1H NMR and 13C NMR). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58%; 8% | With hydrogen; potassium carbonate; In 1,4-dioxane; at 120 - 140℃; under 30003 Torr; for 20h;Autoclave; | General procedure: The suspension of 5 wt% PdO/Co3O4(20 mg, 1.6 mol% Pd atomand 47 mol% Co to substrate) in dioxane (1 mL) in a stainlessautoclave attached a glass tube was stirred at 120C under H2atmosphere (2 MPa) for 2 h. After cooling to RT, aryl halide 1(0.5 mmol), K2CO3(0.5 mmol) and dioxane (1 mL) were added andstirred at 140C for 20 h under CO:H2= 3:1 atmosphere (4 MPa).The reaction mixture was analyzed by GC using tridecane (30 L,0.1 mmol) as an internal standard after filtration through celite toremove the catalyst. The products 2 and 3 were identified by com-parison of the retention time of GC with the authentic samples. Thealdehydes 2a-f and 2h-k were also characterized by1H and13CNMR after chromatographic purifications. Other aldehydes werefound to be difficult to isolate due to low yields and volatilities. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With sodium hydrogensulfite; In N,N-dimethyl acetamide; at 150℃; | General procedure: Sodium hydrogen sulfite (4 mmol) was added to a solution of anthranilamide 1 (2 mmol) and benzaldehyde 2 (2 mmol) in N,N- dimethylacetamide (5 mL). The mixture was heated under continuous stirring at 150 o C for 2-3 h and poured into ice water. The precipitate was then filtered, washed with water followed byethanol, and dried to yield the 2-arylquinazolinones 3-31.#10;#10; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With carbon supported Pd nanoparticles; 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 80℃; under 7500.75 Torr; for 12h;Sealed tube; Green chemistry; | In a 20 ml reactor, place 10 ml acetonitrile, 5mmol o-methyliodobenzene, 15mmol PMHS with weight average molecular weight of 2000, 5.5mmol DBU, 0.01mmol palladium carbon catalyst consisting of a mass ratio of 10: 100 palladium nanoparticles and activated carbon carrier. Seal. Heat to 80 C. Place CO2 to 1MPa. React for 12 hours. The results are as follows: o-methyliodobenzene conversion is 100%; main product o-methylbenzaldehyde, yield is 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With 1,4-diaza-bicyclo[2.2.2]octane; palladium diacetate; dicyclohexyl-carbodiimide; at 100℃; for 2.5h;Sealed tube; | General procedure: Aryl halide (0.5 mmol), Pd(OAc)2 (2.7 mol%), PEG(3.0 mL) and formic acid (3.5 mmol) were transferredinto a round-bottom flask. After, DABCO (1.0 mmol)and DCC (1.0 mmol) were added to the reaction flask,immediately sealed, and the mixture was stirred at100 C. After the reaction was completed the mixturewas diluted with CH2Cl2and filtered and concentrated.The crude product was purified by column chromatographyon silica gel to afford the corresponding product. |
72% | With iodine; triethylamine; triphenylphosphine; In toluene; at 80℃;Inert atmosphere; Sealed tube; | General procedure: A dried 10 mL reaction tube was charged with I 2 (152 mg, 1.2 mmol),PPh 3 (315 mg, 1.2 mmol), and toluene (4 mL) under argon. The mixture was stirred at r.t. for 10 min. Then aryl iodide 1 (1 mmol), 2P-Fe3O4SiO2-Pd(OAc)2 (79 mg, 3 mol%), and Et3N (606 mg, 6 mmol)were added to this solution. After the addition of HCOOH (184 mg, 4mmol), the reaction tube was immediately sealed and the reactionmixture was stirred at 80C for 3-5 h. After cooling to r.t., the Pd catalyst was magnetically separated from the mixture, washed with toluene (2 mL), distilled H2O (2 × 2 mL) and EtOH (2 × 2 mL), dried undervacuum at 80 C, and used directly in the next cycle. The reaction mixture was then filtered and concentrated under vacuum. The residue was purified by silica gel column chromatography (light PE/EtOAc10:1) to afford the desired product 2. |
Tags: 2-Methylbenzaldehyde | Benzene Compounds | Aryls | Aldehydes | Organic Building Blocks | 529-20-4
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P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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