Structure of 3217-47-8
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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.
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Assembly of Multi-Dimensional Molecular Networks through Self-Complementary Halogen-Bonded Tectons
Moghadasnia, Michael P. ; Eckstein, Brian J. ; Balaich, Gary J. ; McGuirk, C. Michael ;
Abstract: A high-fidelity and self-complementary halogen bonding moiety, 2-iodooxazole, was identified using density functional theory-based calculations. Installation of 2-iodooxazole on two geometrically complementary cores using a two-step synthetic approach gave the tectons 1,4-bis(2-iodooxazol-5-yl)benzene (BIOx) and 1,4-bis(2-iodooxazol-5-yl)-2,3,5,6-tetrafluorobenzene (FIOx). Single crystal X-ray diffraction studies have shown that both BIOx and FlOx possess the requisite strength and geometry to assemble into crystalline, multi-dimensional halogen-bonded networks. Control of assembly through chemically intuitive solvent conditions permitted the deliberate assembly of one, two, or three-dimensional halogen-bonded networks. This work demonstrates that through careful design of tectons and crystal-growth conditions, halogen-bonded networks may meet the bar set by hydrogen-bonded analogues.
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Ultralow Surface Tension Solvents Enable Facile COF Activation with Reduced Pore Collapse
Zhu, Dongyang ; Verduzco, Rafael ;
Abstract: Covalent organic frameworks (COFs) are organic, crystalline, highly porous materials attractive for applications such as gas storage, gas separations, catalysis, contaminant adsorption, and membrane filtration. Activation of COFs removes adsorbed solvents and impurities, but common methods for COF activation can result in the collapse of porous structure and loss of accessible surface areas. Here, we present a study of the impact of solvent surface tension on the activation process and demonstrate that activation using the ultralow surface tension solvent perfluorohexane (PFH) is simple and effective for a range of COF materials. We synthesized six different imine-based COFs through imine condensation reactions between tris(4-aminophenyl)benzene (TAPB) or 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and multifunctional di- and tri-benzaldehydes with different aromatic substituents. For each COF, we performed a solvent wash followed by vacuum drying using six solvents varying in surface tension from 11.9 to 72.8 mN m-1. Through powder X-ray diffraction (PXRD) measurements combined with nitrogen adsorption and desorption anal., we found that some COF chemistries readily lost their porosity during activation with higher surface tension solvents while others were more robust. However, all COFs could be effectively activated using PFH to produce materials with excellent crystallinity and high surface areas, comparable to those for samples activated using supercritical CO2. This work demonstrates that the solvent surface tension used during activation has a strong impact on the potential pore collapse, and activation using PFH provides a simple and effective activation method to produce COFs with excellent crystallinities and pore structures.
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Keywords: COFs ; activation ; perfluorohexane ; pore collapse ; ultralow surface tension solvents
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CAS No. : | 3217-47-8 |
Formula : | C8H2F4O2 |
M.W : | 206.09 |
SMILES Code : | O=CC1=C(F)C(F)=C(C=O)C(F)=C1F |
MDL No. : | MFCD08704256 |
InChI Key : | WJHRAPYKYJKACM-UHFFFAOYSA-N |
Pubchem ID : | 10420501 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
34.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.66 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.46 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.87 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.36 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.09 |
Solubility | 1.67 mg/ml ; 0.00812 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.57 |
Solubility | 5.61 mg/ml ; 0.0272 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.42 |
Solubility | 0.0787 mg/ml ; 0.000382 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
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) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.67 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 |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.28 |
* 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 |
---|---|---|
[Example 1]; In a conical flask, 20.6 g of 95% sulfuric acid was slowly added dropwise to 70 g (2.2 mol) of methanol with ice cooling. Then, into a 300-ml glass autoclave, the resulting sulfuric acid/methanol solution and a 5% Rh/C catalyst (available from NE Chemcat Corporation, hydrous product) in an amount of 0.25 g on a dry weight basis were charged. The system was purged with hydrogen to make a hydrogen pressure 0.1 MPa at room temperature. Heating of the autoclave and stirring of the contents in the EPO <DP n="20"/>autoclave were started, and the temperature was increased to 400C and was held constant for 1 hour. After the autoclave was cooled, 10 g (50 mmol) of tetrafluoroterephthalonitrile (available from Tokyo Kasei Kogyo Co., Ltd.) was fed to the autoclave, and the temperature was raised to 700C in a nitrogen atmosphere. At 700C, introduction of hydrogen was started. The reaction pressure was controlled so that the hydrogen absorption rate should become not more than 10 ml/min. After a lapse of 6 hours and 30 minutes, absorption of hydrogen ceased. The quantity of hydrogen absorbed was 119% of the theoretical quantity of hydrogen absorbed. The reaction solution was filtered to separate the catalyst, and methanol was distilled off at atmospheric pressure. Thereafter, 100 g of water was added to the residue, and the mixture was refluxed by heating at an internal temperature of 1000C for 60 minutes. Then, methanol formed by hydrolysis of acetal was distilled off at atmospheric pressure. When the top temperature of the distillation reached 99C, the distillation was finished, and the resulting solution was cooled to room temperature. Then, the solution was extracted 3 times each with 30 g of toluene . EPO <DP n="21"/>From the toluene extract, a small amount of a sample was withdrawn, and it was subjected to GC analysis. As a result of the analysis, a peak of the tetrafluoroterephthalonitrile as a raw material was below the detection limit, the amount of tetrafluoroterephthalaldehyde was 92.0 mol%, the amount of 2, 3, 5, 6-tetrafluorobenzene was 0.94 mol%, and the amount of 2, 3, 5, 6-tetrafluorobenzonitrile was 0.79 mol%. On the other hand, the aqueous phase was neutralized and then subjected to GC analysis. As a result of the analysis, presence of 3.39 mol% of 2, 3, 5, 6-tetrafluorobenzylamine was confirmed. The results are set forth in Table 1. [Example 2]The same operations as in Example 1 were carried out, except that as a catalyst a 5% Pd/C catalyst (available from NE Chemcat Corporation, hydrous product) was charged in an amount of 0.25 g on a dry weight basis. After a lapse of 3.3 hours, absorption of hydrogen ceased. The quantity of hydrogen absorbed was 117% of the theoretical quantity of hydrogen absorbed. Treatment of the reaction solution was carried out in the same manner as in Example 1.From the toluene extract, a small amount of a sample was withdrawn, and it was subjected to GC analysis. As a EPO <DP n="22"/>result of the analysis, a peak of the tetrafluoroterephthalonitrile as a raw material was below the detection limit, and the amount of tetrafluoroterephthalaldehyde was 68.9 mol%. On the other hand, the aqueous phase was neutralized and then subjected to GC analysis. As a result of the analysis, presence of14.8 mo1% of 2, 3, 5, 6-tetrafluorobenzylamine was confirmed.The results are set forth in Table 1. [Example 2]; The same operations as in Example 1 were carried out, except that as a catalyst a 5% Pd/C catalyst (available from NE Chemcat Corporation, hydrous product) was charged in an amount of 0.25 g on a dry weight basis. After a lapse of 3.3 hours, absorption of hydrogen ceased. The quantity of hydrogen absorbed was 117% of the theoretical quantity of hydrogen absorbed. Treatment of the reaction solution was carried out in the same manner as in Example 1.From the toluene extract, a small amount of a sample was withdrawn, and it was subjected to GC analysis. As a EPO <DP n="22"/>result of the analysis, a peak of the tetrafluoroterephthalonitrile as a raw material was below the detection limit, and the amount of tetrafluoroterephthalaldehyde was 68.9 mol%. On the other hand, the aqueous phase was neutralized and then subjected to GC analysis. As a result of the analysis, presence of14.8 mo1% of 2, 3, 5, 6-tetrafluorobenzylamine was confirmed.The results are set forth in Table 1.; [Example 3] The same operations as in Example 1 were carried out, except that the temperature of the pretreatment of the catalyst with hydrogen was changed from 400C to 500C.After a lapse of 5.5 hours, absorption of hydrogen ceased.The quantity of hydrogen absorbed was 106% of the theoretical quantity of hydrogen absorbed. Treatment of the reaction solution was carried out in the same manner as in Example 1.From the toluene extract, a small amount of a sample was withdrawn, and it was subjected to GC analysis. As a result of the analysis, a peak of the tetrafluoroterephthalonitrile as a raw material was ... | ||
[Example 7]; The same operations as in Example 1 were carried out, except that the catalyst used was changed from the 5% Rh/C catalyst (available from NE Chemcat Corporation, hydrous product) to a 2% Rh/C catalyst (available from NE Chemcat EPO <DP n="26"/>Corporation, hydrous product) . After a lapse of 7.3 hours, absorption of hydrogen ceased. The quantity of hydrogen absorbed was 114% of the theoretical quantity of hydrogen absorbed. Treatment of the reaction solution was carried out in the same manner as in Example 1.From the toluene extract, a small amount of a sample was withdrawn, and it was subjected to GC analysis. As a result of the analysis, a peak of the tetrafluoroterephthalonitrile as a raw material was below the detection limit, the amount of tetrafluoroterephthalaldehyde was 88.6 mol%, the amount of 2, 3, 5, 6-tetrafluorobenzene was 1.15 mol%, and the amount of 2, 3, 5, 6-tetrafluorobenzonitrile was 2.63 ralphaol%. On the other hand, the aqueous phase was neutralized and then subjected to GC analysis. As a result of the analysis, presence of 2.36 mol% of 2, 3, 5, 6-tetrafluorobenzylamine was confirmed. The results are set forth in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[Comparative Example 1]; The same operations as in Example 1 were carried out, except that the amount of the catalyst used was changed from 0.25 g to 0.05 g on a dry weight basis. After a lapse of 7.0 hours, absorption of hydrogen ceased. The quantity of hydrogen absorbed was 83% of the theoretical quantity of hydrogen absorbed. Treatment of the reaction solution was carried out in the same manner as in Example 1. EPO <DP n="28"/>From the toluene extract, a small amount of a sample was withdrawn, and it was subjected to GC analysis. As a result of the analysis, the tetrafluoroterephthalonitrile as a raw material remained in an amount of 21.0 mol%, and tetrafluoroterephthalaldehyde was obtained in an amount of only 5.0 mol%. The amount of 2, 3, 5, 6-tetrafluorobenzene was 0.65 mol%, the amount of 2,3,5,6- tetrafluorobenzonitrile was 0.53 mol%, and 1-cyano- 2, 3, 5, 6-tetrafluorobenzaldehyde wherein a nitrile group on only one side had reacted was obtained in an amount of 63.1 mol%. On the other hand, the aqueous phase was neutralized and then subjected to GC analysis. As a result of the analysis, presence of 2.88 mol% of 2,3,5,6- tetrafluorobenzylamine was confirmed. The results are set forth in Table 2.; [Comparative Example 3]; The same operations as in Example 1 were carried out, except that the amount of sulfuric acid used was changed from 20.6 g to 5.15 g (50 mmol). After a lapse of 4.2 hours, absorption of hydrogen ceased. The quantity of hydrogen absorbed was 47% of the theoretical quantity of hydrogen absorbed. Treatment of the reaction solution was carried out in the same manner as in Example 1.From the toluene extract, a small amount of a sample was withdrawn, and it was subjected to GC analysis. As a result of the analysis, a peak of the tetrafluoroterephthalonitrile as a raw material was below EPO <DP n="30"/>the detection limit, and tetrafluoroterephthalaldehyde was obtained in an amount of only 14.5 mol%. The amount of 2, 3, 5, 6-tetrafluorobenzene was 0.81 mol%, the amount of 2, 3, 5, 6-tetrafluorobenzonitrile was 0.67 mol%, and 1- cyano-2, 3, 5, 6-tetrafluorobenzaldehyde wherein a nitrile group on only one side had reacted was obtained in an amount of 54.0 mol%. On the other hand, the aqueous phase was neutralized and then subjected to GC analysis. As a result of the analysis, presence of 0.04 mol% of 2,3,5,6- tetrafluorobenzylamine was confirmed. The results are set forth in Table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[Comparative Example 4]; The same operations as in Example 1 were carried out, except that the reaction temperature was changed from 7O0C to 12O0C. After a lapse of 8.0 hours, absorption of hydrogen ceased. The quantity of hydrogen absorbed was 103% of the theoretical quantity of hydrogen absorbed. Treatment of the reaction solution was carried out in the same manner as in Example 1. From the toluene extract, a small amount of a sample was withdrawn, and it was subjected to GC analysis. As a result of the analysis, a peak of the tetrafluoroterephthalonitrile as a raw material was below the detection limit, and tetrafluoroterephthalaldehyde was EPO <DP n="31"/>obtained in an amount of only 2.6 mol%. The amount of 2, 3, 5, beta-tetrafluorobenzene was 1.08 mol%, the amount of 2, 3, 5, 6-tetrafluorobenzonitrile was 0.87 mol%, and 1- cyano-2, 3, 5, 6-tetrafluorobenzaldehyde wherein a nitrile group on only one side had reacted was obtained in an amount of 42.2 mol%. On the other hand, the aqueous phase was neutralized and then subjected to GC analysis. As a result of the analysis, the amount of 2,3,5,6- tetrafluorobenzylamine was below the detection limit. The results are set forth in Table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;cobalt R400; In toluene; at 120 - 150℃; under 3750.38 - 5625.56 Torr; for 10.5h;Autoclave;Product distribution / selectivity; | In a 100 ml autoclave, 6.0 g (29.1 mmol) of 2,3,5,6-tetrafluorobenzene-1,4-dicarbaldehyde, 24.0 g of toluene and 0.6 g of a sponge cobalt catalyst (R-400 manufactured by Nikko Rica Corporation) having been separately subjected to methanol replacement and toluene replacement in advance were placed.First, the autoclave was purged with nitrogen at room temperature and then purged with hydrogen. Subsequently, the temperature of the autoclave was raised to 120 C., then hydrogen was fed to the autoclave with maintaining the pressure at 0.5 MPa, and the reaction was carried out at a temperature of 120 C. for 5 hours. The ratio of absorption of hydrogen at this time was 63%. The temperature of the autoclave was further raised up to 150 C. over a period of 20 minutes, then hydrogen was fed to the autoclave with maintaining the pressure at 0.75 MPa, and the reaction was further, carried out at a temperature of 150 C. for 5 hours and 10 minutes. The ratio of absorption of hydrogen through the whole reaction was 102%. Then, feeding of hydrogen was terminated, and the autoclave was cooled to room temperature. Subsequently, the catalyst was filtered out, and the reaction liquid was taken out.A small amount of a sample was withdrawn and subjected to GC analysis. As a result of the analysis, a peak of the 2, 3, 5, 6-tetrafluorobenzene-1,4-dicarbaldehyde as a raw material was not more than the limit of detection, the formation ratio of 2,3,5,6-tetrafluoro-4-methylbenzyl alcohol was 80.8%, the formation ratio of 1,4-dimethyl-2,3,5,6-tetrafluorobenzene was 8.6%, and the formation ratio of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol was 6.9%. |
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