Structure of Iodobenzene
CAS No.: 591-50-4
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Sustainable methodologies for synthesis of small organic molecules using micellar catalysis
Deborah Sam Ogulu ;
Abstract: Organic synthesis is a critical process in the creation of small molecule pharmaceuticals and agrochemicals. However, most methods for synthesizing these small molecules rely on toxic organic solvents as the reaction medium which account for approximately 80% of pharmaceutical waste. Moreover, many catalytic reactions require expensive endangered precious metals like palladium and costly metals. This dissertation presents research that aims to develop sustainable, eco-friendly reaction conditions to address these issues. Chapter 1 provides an overview of green and sustainable chemistry and chemistry in water. It explains what sustainability entails and the drive towards greener synthetic methods. Also included is the introduction to the concept of chemistry in water, the different types of roles of water in chemistry, and the development of micellar catalysis – including its evolution, applications, current challenges, and future directions. Chapter 2 discusses the development of a ligand-free bimetallic nanocatalyst for the hydrogenation of unsaturated enones. This ligand-free nanocatalyst was prepared from nickel and ppm loading of palladium and was stabilized by harnessing the structural features of the amphiphile, PS-750-M. The physical properties of the nanoparticles were evaluated and thoroughly characterized using different analytical techniques like HRTEM, XPS, and TGA. Chapter 3 describes the application of a copper catalyst in the hydroboration of unsymmetrical internal alkynes with high regioselectivity under aqueous micellar conditions. The methodology was amenable to internal alkynes with diverse functional groups and provides a unique route to access β selective alkenyl boronates. Chapter 4 showcases the development of a protocol towards coupling of aryl boronic acids and primary amines under aqueous micellar conditions using an inexpensive nickel catalyst and oxygen balloon. The developed methodology provides another way to access amines under more sustainable reaction conditions. Chapter 5 describes the use of ppm palladium and copper catalysts immobilized on silica for the catalytic dehydration of amides to nitriles. The protocol employs acetonitrile as the additive and the reaction is performed using aqueous PS-750-M as the reaction medium.
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Guo, Sheng ; Wu, Yifan ; Luo, Shao-Xiong Lennon ; Swager, Timothy M. ;
Abstract: Heterogenous catalysts with confined nanoporous catalytic sites are shown to have high activity and size selectivity. A solution-processable nanoporous organic polymer (1-BPy-Pd) catalyst displays high catalytic performance (TON > 200K) in the heterogeneous Suzuki–Miyaura coupling (SMC) reaction and can be used for the preparation of the intermediates in the synthesis of pharmaceutical agents. In comparison to the homogeneous catalyst analogue (2,2′-BPy)PdCl2, the heterogenous system offers size-dependent catalytic activity when bulkier substrates are used. Furthermore, the catalyst can be used to create catalytic impellers that simplify its use and recovery. We found that this system also works for applications in heterogenous Heck and nitroarenes reduction reactions. The metal-binding nanoporous polymer reported here represents a versatile platform for size-selective heterogeneous and recyclable catalysts.
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Keywords: nanoporous organic polymer ; heterogeneous catalyst ; Suzuki−Miyaura coupling reaction ; size-selective reaction ; catalyst processing
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Purchased from AmBeed: 128796-39-4 ; 10365-98-7 ; 98-80-6 ; 556-96-7 ; 171663-13-1 ; 71597-85-8 ; 402-43-7 ; 2042-37-7 ; 22385-77-9 ; 16419-60-6 ; 15862-18-7 ; 87199-15-3 ; 171408-84-7 ; 643-58-3 ; 591-50-4 ; 76911-73-4 ; 398-36-7 ; 14871-92-2 ; 5720-07-0 ; 945976-76-1 ; 366-18-7 ; 2920-38-9 ; 623-00-7 ; 24973-49-7 ; 588-59-0 ; 128796-39-4 ; 5723-93-3 ; 17057-88-4 ; 126485-55-0
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CAS No. : | 591-50-4 |
Formula : | C6H5I |
M.W : | 204.01 |
SMILES Code : | IC1=CC=CC=C1 |
MDL No. : | MFCD00001029 |
InChI Key : | SNHMUERNLJLMHN-UHFFFAOYSA-N |
Pubchem ID : | 11575 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.16 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.97 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.21 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.94 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.79 |
Solubility | 0.0333 mg/ml ; 0.000163 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.92 |
Solubility | 0.243 mg/ml ; 0.00119 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.35 |
Solubility | 0.0907 mg/ml ; 0.000445 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.24 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.14 |
* 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 |
---|---|---|
38% | With aluminum (III) chloride In carbon disulfide at 5 - 10℃; for 24 h; Inert atmosphere | Iodobenzene (10Og, 0.49 mol) was taken in a dry 1 L 3 neck flask equipped with a N2 inlet and to it 200 ml of CS2 was added. The contents were cooled to 0-50C and then AICI3 (80 g, 0.6 moles) and subsequently propionyl chloride (60 g, 0.64 mol) were added while keeping the temperature (internal) at 5-100C. The contents were stirred for 24 hrs.The reaction mixture was poured into a 5 liter plastic beaker containing 1 L of 10percent HCI + 1 Kg of crushed ice. The resultant slurry was extracted with 1 L of ethyl acetate. The organic layer was separated and washed with 2x500 ml of water and 500 ml of brine. The organic layer was dried over sodium sulphate and concentrated at 400C to give 4'-iodopropiophenone (48 g, 38percent).1H NMR (500 MHz, CDCI3-d) 7.82 (d, 2H), 7.67 (d, J = 8.30 Hz, 2H), 2.96 (q, J = 7.00 Hz, 2H), 1.22 (t, J = 7.32 Hz, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.4% | With copper; potassium carbonate In <i>N</i>-methyl-acetamide | 368.1 1-(4-anilinophenyl)ethanone 4-amino-acetophenone (4.87 g; 36.0 mmol) is dissolved in dimethylformamide (75 ml). 15 g (0.108 mol) of potassium carbonate (previously dried at 170° C. under an argon atmosphere), 7.236 g (36.0 mmol) of iodobenzene, 0.4 g of copper in powder form and a catalytic quantity of copper iodide are added. The reaction mixture is taken to reflux for 12 hours. After leaving the reaction medium to return to ambient temperature, it is filtered on celite and poured into ice-cold water. After extraction with ethyl acetate, the organic phase is washed with water before being dried over magnesium sulphate, filtered and concentrated under vacuum. The product obtained is purified by crystallization from heptane in order to produce a yellow solid with a yield of 53.4percent. Melting point: 105° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.4% | With potassium carbonate In <i>N</i>-methyl-acetamide | 335.1 1-(4-anilinophenyl)ethanone 4-amino-acetophenone (4.87 g; 36.0 mmol) is dissolved in dimethylformamide (75 ml). 15 g (0.108 mol) of potassium carbonate (previously dried at 170° C. under an argon atmosphere), 7.236 g (36.0 mmol) of iodobenzene, 0.4 g of copper powder and a catalytic quantity of copper iodide are added. The reaction mixture is taken to reflux for 12 hours. After leaving the reaction medium to return to ambient temperature, the latter is filtered on celite and poured into ice-cooled water. After extraction with ethyl acetate, the organic phase is washed with water before being dried over magnesium sulphate, filtered and concentrated under vacuum. The product obtained is purified by crystallization from heptane in order to produce a yellow solid with a yield of 53.4percent. Melting point: 105° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tetrakis(triphenylphosphine) palladium(0) In toluene at 120℃; for 16 h; Inert atmosphere | In the same procedure as in Synthesis Example 2, the compound 2 was prepared from a solution containing the compound 1 (28.5 g, 125 mmol), tetrahydrofuran (125ml), the n-BuLi-hexane solution (74.9 ml, mole number of n-BuLi in the solution: 125 mmol, molarity (mole number of n-BuLi/solution amount): 1.67M) and zinc chloride (28.4 g, 208 mmol) dissolved in tetrahydrofuran (208 ml). After preparing the compound 2, the compound 2 was put into a three-necked flask, to which an oil-sealed rotary pump was connected through a solvent trap that is cooled using a solvent of dry ice/acetone. The three-necked flask was heated to about 40 degrees C under reduced pressure to remove the solvent (310 ml) from the reaction system (the solvent removal step). A removal amount of the solvent herein is an amount collected by the solvent trap. Subsequently, nitrogen was put into the reaction system to return to the normal pressure. Toluene (104 ml) was put into the reaction system (toluene addition step). Next, iodobenzene (21.3g, 104 mmol) and Pd(PPh3)4 (2.89 g, 2.5 mmol) were added thereto and reacted at 120 degrees C for 16 hours under nitrogen atmosphere. [0151] A relationship of the solvent amounts in the reaction system in Synthesis Example 4 is shown in Table 1. Herein, a relationship between the total volume VA [liter] of tetrahydrofuran (i.e., the ether solvent having at most 5 carbon atoms) and the mole number Nf2 [mol] of iodobenzene is represented below according the same calculation as in Synthesis Example 3 as shown in Table 1. The relationship of the numerical formula (3) was satisfied. Further, a relationship between a volume VB [liter] of toluene (i.e., an aromatic hydrocarbon solvent having 7 carbon atoms) and a mole number Nf2 [mol] of iodobenzene is represented below as shown in Table 1. The relationship of the numerical formula (5) was satisfied. There is a possibility that n-hexane (i.e., an aliphatic hydrocarbon having 6 carbon atoms) is contained in the reaction system even after the solvent removal step in Synthesis Example 4. However, since the volume of n-hexane after the solvent removal step is less than the volume of toluene subsequently added, the relationship of the numerical formula (5) is still satisfied even in consideration of n-hexane. The same applies to Examples 3 and 4 described later. Accordingly, Synthesis Example 4 was conducted under the reaction condition of satisfying the relationships of the numerical formulae (3) and (5). [0152] After the reaction, a small amount of water was added to the sample to deactivate the reaction. The mixture was diluted with dichloromethane (300 ml). An aqueous solution of tetrasodium ethylenediaminetetraacetate dihydrate (129.9 g, 312 mmol) was added to the diluted mixture and stirred in a separating funnel. An aqueous sodium hydroxide was further added thereto to adjust an aqueous phase to pH10 or more. A dichloromethane phase was collected. The aqueous phase was extracted with dichloromethane several times. The extract was dried over anhydrous magnesium sulfate, filtrated and concentrated. The obtained product was refined by silica-gel chromatography (toluene:ethyl acetate=95:5 (volume ratio)) and was further recrystallized in a mixture solvent of hexane/ethyl acetate to obtain a white solid. The compound 4 was identified according to 1H-NMR and FD-MS. Yield: 24.7 g Yield Rate: 78percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With 10 molpercent nickel based 2,5-dihydroxyterephthalic acid metal organic framework-74; In diethylene glycol dimethyl ether; at 160℃; for 18h;Sealed tube; | General procedure: In a typical experiment, a predetermined amount of Ni-MOF-74 was added to the 8 mL vial containing a mixture of iodobenzene (0.1030 g, 0.5 mmol), benzothiazole (0.1379 g, 1.0 mmol), Li2CO3 or KCl (1.0 mmol), and diphenyl ether (0.085 g, 0.5 mmol) as standard. 1-Methoxy-2-(2-methoxyethoxy)ethane (diglyme) (1 mL) was added and vial was tightly capped. Reaction mixture was heated at 160°C for 24 h. The catalyst loading was based on the molar ratio of nickel/iodobenzene. The reaction yield was monitored by withdrawing aliquots from the reaction mixture at different time intervals, diluting with ethylacetate (2 mL), quenching with an aqueous KOH solution (1percent, 1 mL), and then drying over anhydrous Na2SO4 before analyzing by GC with reference to diphenyl ether (internal equation with pure product), and further confirming product identity by GC?MS and NMR. To investigatethe recycle ability of Ni-MOF-74, the catalyst was filtered from the reaction mixture after the experiment, washed with ethylacetate, water, THF, and dried at 140°C under vacuum in 8 h. For the leaching test, a catalytic reaction was stopped after 12 h, analyzed by GC, and filtered to remove the solid catalyst. The reaction solution was then stirred for a further 12 h. Reaction progress, if any, was monitored by GC as previously described. |
67% | With (1-(2-(tert-butylamino)ethyl)-3-mesityl-2,3-dihydro-1H-imidazol-2-yl)copper(I) iodide; lithium tert-butoxide; In N,N-dimethyl-formamide; at 140℃; for 8h;Glovebox; | General procedure: The product 12a is a representative reaction. To a vial (5 mL) containing caffeine (0.5 mmol), iodobenzene (1.0 mmol), catalyst 3e (0.05 mmol), and LiOtBu (1.0 mmol) was added DMF (1.0 mL) solvent under a glovebox atmosphere. After the substances were completely dissolved, the vial was screw-capped, taken outside the glovebox and heated at 140 °C for 8 h. The resulting mixture was filtered through Celite and washed with dichloromethane. The filtrate solution was concentrated in vacuo to afford the crude product, which was further purified by column chromatography using hexane/ethyl acetate as eluent to furnish 12a in 80percent yield. |
46% | With potassium phosphate; Cu2(4,4?-biphenyldicarboxylate)2(4,4?-bipyridine); In Hexadecane; N,N-dimethyl-formamide; at 120℃; for 3h;Green chemistry; | General procedure: In a typical experiment, a pre-determined amount of Cu2(BPDC)2(BPY) was added to theflask containing a solution of iodobenzene (0.112 mL, 1 mmol),benzoxazole (0.238 g, 2 mmol), K3PO4(0.532 g, 2 mmol) and n-hexadecane (0.1 mL) as internal standard in DMF (4 mL). Thecatalyst concentration was calculated based on the molar ratio ofcopper/iodobenzene. The reaction mixture was stirred at 100Cunder an argon atmosphere for 180 min. The reaction conver-sion was monitored by withdrawing aliquots from the reactionmixture at different time intervals, quenching with an aqueousNaOH solution (5percent, 1 mL), drying over anhydrous Na2SO4, analyz-ing by GC with reference to n-hexadecane, and further confirmingproduct identity by GC?MS. To investigate the recyclability ofCu2(BPDC)2(BPY), the catalyst was filtered from the reaction mix-ture after the experiment, washed with copious amounts of DMF,dried under air at room temperature for 1 h, and reused if neces-sary. For the leaching test, a catalytic reaction was stopped after30 min, analyzed by GC, and filtered to remove the solid catalyst.The reaction solution was then stirred for a further 150 min. Reac-tion progress, if any, was monitored by GC as previously described. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate;bis(tri-t-butylphosphine)palladium(0); In 1,2-dimethoxyethane; at 100℃; for 14.0h; | A. To a solution of ethyl isonipecotate (1.00 g, 6.36 mmol) in 10 mL of anhydrous DME was added iodobenzene (1.95 g, 9.54 mmol), bis(tri-t-butylphosphine)palladium(0) (0.33 g, 0.636 mmol), and potassium phosphate (2.70 g, 12.7 mmol). The reaction mixture was heated to 100° C. and stirred for 14 hours. Solids were filtered off from the resulting mixture and the collected filtrate was concentrated under reduced pressure to provide the crude product, which was then redissolved into 10 mL of methanol. 2 mL of 1N lithium hydroxide was added to hydrolyze the ester at 80° C. for 3 hours. Solvent was evaporated off and the basic residue was acidified by 2N HCl. The aqueous mixture was extracted with EtOAc. The combined organic layers was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to afford the crude product which was then purified by flash column chromatography with CH2Cl2 and MeOH to yield 1-phenyl-piperidine-4-carboxylic acid as yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25.9 g (94.2%) | With chlorine; In chloroform; | EXAMPLE 6 Preparation of iodobenzene dichloride. Chlorine gas is bubbled through a solution of iodobenzene (20.4 g; 0.1 mole) in chloroform (100 ml) while the temperature of the reaction mixture is maintained at -5° C. In about 10 minutes a yellow solid precipitates and is removed by filtration. The filtrate is then further treated with chlorine gas until the formation of yellow solid ceases. The solid fractions are combined and air dried to afford 25.9 g (94.2percent) of title product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With copper(l) iodide; 18-crown-6 ether; potassium carbonate; In DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone); at 170℃; for 20h; | Synthesis of Intermediate E; 3.25 g (10.0 mmol) of 3, 6-dibromocarbazole, 10.2 g (50.0 mmole) iodobenzene, 190 mg (1.0 mmole) of Cul, 132 mg (0.5 mmole) of 18-C-6, 2.76 g (20.0mmole) of K2CO3 were dissolved in 50 mL of DMPU, and stirred at 170°C for 20 hours. The mixture was cooled to room temperature and 50 mL of diethylether was added thereto. Then the mixture was washed with plenty of water and ammonium hydroxide solution. A collected organic layer was dried over MgSO4 to evaporate the solvent. The residue was purified using silica gel column chromatography to obtain 3.40 g of white solid Intermediate E (Yield: 85 percent). (NMR (CDCl3, 400MHz) delta (ppm) 7.92 (m, 2H), 7.55-7.47 (m, 6H), 7.36-7.16 (m, 3H); 13C NMR (CDCl3, 100MHz) delta (ppm) 142.6, 137.6, 130.2, 129.8, 127.4, 127.0, 122.8, 122.5, 115.3, 111.3). |
75% | With tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine; sodium t-butanolate; In toluene; at 100℃; for 24h; | To a round bottom flask Sub 2-1-6 (6.5g, 20mmol), Sub 2-1-2-1 (4.1g, 20mmol),Pd2 (dba) 3 (0.9g, 1mmol), PPh3 (0.5g, 2mmol ), NaOt-Bu (5.8g, 60mmol), were addedto toluene (210mL), respectively, and refluxed under stirring for 24 hours at 100 ° C.The organic layer was dried and the ether was extracted with water over MgSO4 andconcentrated and to the resulting organic silicagel column and recrystallized from a Sub2-1-7-1 6.0g (yield: 75percent) was obtained. |
3.27 g | With palladium diacetate; tris-(o-tolyl)phosphine; sodium t-butanolate; In toluene; | 2.5 g (14.9 mmol) ofcarbazole was used (utilized) to perform an NI3S bromination to synthesize 2,5-dibromocar- bazole. Then, the 2,5-dibromocarbazole and iodinated phenyl were used (utilized) to synthesize 3.72 g (9.28 mmol) of Intermediate E through a buchwald reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With cesium hydroxide; In dimethyl sulfoxide; at 120℃; for 0.666667h;Sealed tube; | A stirred solution of <strong>[886766-28-5]4,7-diaza-spiro[2.5]octane-7-carboxylic acid tert-butyl ester</strong> (0.1 g, 0.471 mmol) [C.A.S. 886766-28-5] , iodobenzene (0.026 ml, 0.236) and CsOH (0.079 g, 0.471 mmol) in DMSO (1 ml) was heated in a sealed tube at 1200C for 20 min. After cooling, additional <strong>[886766-28-5]4,7-diaza-spiro[2.5]octane-7-carboxylic acid tert-butyl ester</strong> (2 eq.) was added, and the mixture was then heated at 1200C for 20 min. The mixture was cooled.The mixture was washed with NH4Cl (aqueous sat. solution) was added and extracted with Et2O. The organic phase was separated, washed with water, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by manifold (Sep-Pak.(R). silica cartridge; DCM as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate D61 (0.021 g, 31percent) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.6% | With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 120℃; for 16h;Inert atmosphere; | [136] N-(2,4-dimethylphenyl)-2,4-dimethyl-N-phenylaniline (Compound 15): A mixture of <strong>[19616-28-5]bis(2,4-dimethylphenyl)amine</strong> (Compound 14) (9.4 g, 41 .8 mmol), iodobenzene (17.14 g, 84 mmol), Pd(OAc)2 (0.47 g, 2.1 mmol), P(t-Bu)3 (0.848 g, 4.2 mmol), sodium tert-butoxide (7.68 g, 80 mmol) in toluene (120 mL) was degassed and heated at 120°C for 16 hours. The resulting mixture was poured into ethyl acetate (250 mL), washed with brine, dried over Na2S04, loaded on silicagel and purified by flash column using eluent of hexanes. After removal of solvent, an oil (Compound 15) was obtained (12.4 g, in 98.6percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.5% | With copper(l) iodide; caesium carbonate; In N,N-dimethyl-formamide; at 110℃; for 12h;Inert atmosphere; | A.3,6-dibromocarbazole (200 mg, 0.62 mmol) was dissolved in DMF solvent,Then iodobenzene (188.3 mg, 0.92 mmol) was added,DL-piperidinecarboxylic acid (11.88 mg, 0.09 mmol),Cuprous oxide (8.27 mg, 0.04 mmol),Cesium carbonate (299.75 mg, 0.92 mmol),Under nitrogen protection,The reaction system was placed at 110 ° C under reflux for 12 h,After the reaction is complete,Ethyl acetate extraction,Organic layer washed three times,Dried over anhydrous sodium sulfate,The solvent is evaporated under reduced pressure;The crude product was purified by column chromatography with ethyl acetate and petroleum ether mixed solvent (20: 1)To obtain compound 3,6-dibromo-9-phenylcarbazole (white solid, 225 mg, yield 90.5percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 120℃; under 7500.75 Torr; for 20h;Inert atmosphere; Autoclave; | General procedure: A 12mL vial was charged with MCM-41-2P-Pd(OAc)2 (2mol%), 2-aminobenzamide (1mmol), aryl iodide (1mmol) (if solid) and a stirring bar. Then, DMF (2mL), aryl iodide (1mmol) (if liquid) and DBU (2mmol) were injected by syringe under an argon atmosphere. The vial was placed in an alloy plate, which was transferred into a 300mL Parr Instruments 4560 series autoclave under an argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10bar CO was fixed at ambient temperature. The autoclave was heated for 20hat 120C. After completion of the reaction, the autoclave was cooled to room temperature and the pressure was released carefully. The reaction mixture was diluted with ethyl acetate (10mL) and filtered. The palladium catalyst was washed with distilled water (2×5mL) and acetone (2×5mL), and reused in the next run. The filtrate was concentrated in vacuo and the pure product was isolated by either washed with water, ethyl acetate and finally hexane or recrystallization from MeOH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 120℃; under 7500.75 Torr; for 20h;Inert atmosphere; Autoclave; | General procedure: A 12mL vial was charged with MCM-41-2P-Pd(OAc)2 (2molpercent), 2-aminobenzamide (1mmol), aryl iodide (1mmol) (if solid) and a stirring bar. Then, DMF (2mL), aryl iodide (1mmol) (if liquid) and DBU (2mmol) were injected by syringe under an argon atmosphere. The vial was placed in an alloy plate, which was transferred into a 300mL Parr Instruments 4560 series autoclave under an argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10bar CO was fixed at ambient temperature. The autoclave was heated for 20hat 120°C. After completion of the reaction, the autoclave was cooled to room temperature and the pressure was released carefully. The reaction mixture was diluted with ethyl acetate (10mL) and filtered. The palladium catalyst was washed with distilled water (2×5mL) and acetone (2×5mL), and reused in the next run. The filtrate was concentrated in vacuo and the pure product was isolated by either washed with water, ethyl acetate and finally hexane or recrystallization from MeOH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With copper(I) oxide; potassium phosphate; In 1-methyl-pyrrolidin-2-one; at 160℃; for 12h;Inert atmosphere; Schlenk technique; | General procedure: A mixture of Cu2O (0.02 mmol), K3PO4 (0.4 mmol), indole-2-carboxylic acid (1) (0.2 mmol), and aryl halide (2) (0.2 mmol) in NMP (2.0 mL) was stirred at room temperature under a N2 atmosphere. The mixture was then heated to 160 °C and stirred at this temperature for 12 h. After completion of the reaction, the mixture was cooled to room temperature and diluted with EtOAc. The mixture was washed with H2O and aq NaCl, dried over MgSO4 and filtered. After evaporation of the solvent, the residue was purified by preparative thin-layer chromatography on silica gel with PE/EtOAc (50:1) as eluent to give the product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With trifluorormethanesulfonic acid; palladium diacetate; silver trifluoroacetate; acetic acid; glycine; at 100℃; for 24h;Sealed tube; | General procedure: A sealed tube with magnetic stir bar was charged with substrate 1 (0.24 mmol), glycine (0.1 mmol, 7.5 mg), Pd(OAc)2 (0.02 mmol, 4.45 mg), AgTFA (0.24 mmol, 53.01 mg) and 2 (0.2 mmol) under air. After addition of AcOH (2 mL) as solvent, TfOH (0.1 mmol, 15.0 mg) was added. The reaction mixture was allowed to stir at 100 C for 24 hours. Upon completion, the reaction mixture was cooled to room temperature, diluted with DCM, and then extracted with saturated NaHCO3 aqueous solution. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The crude residue was purified by column chromatography on silica gel using PE as the eluent to afford the desired products. |
Tags: 591-50-4 synthesis path| 591-50-4 SDS| 591-50-4 COA| 591-50-4 purity| 591-50-4 application| 591-50-4 NMR| 591-50-4 COA| 591-50-4 structure
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Code | Phrase |
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Code | Phrase |
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P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
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P230 | Keep wetted |
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P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
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P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
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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. |
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P282 | Wear cold insulating gloves/face shield/eye protection. |
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P285 | In case of inadequate ventilation wear respiratory protection. |
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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: |
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P321 | |
P322 | |
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P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
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P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
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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. |
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P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
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P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
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P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
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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 |
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