Structure of 2,5-Hexanedione
CAS No.: 110-13-4
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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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CAS No. : | 110-13-4 |
Formula : | C6H10O2 |
M.W : | 114.14 |
SMILES Code : | CC(CCC(C)=O)=O |
MDL No. : | MFCD00008792 |
InChI Key : | OJVAMHKKJGICOG-UHFFFAOYSA-N |
Pubchem ID : | 8035 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Warning |
Hazard Statements: | H227-H302-H315-H319-H361-H373 |
Precautionary Statements: | P201-P202-P210-P260-P264-P270-P280-P301+P312+P330-P302+P352-P305+P351+P338-P308+P313-P332+P313-P337+P313-P370+P378-P403+P235-P405-P501 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.67 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 31.36 |
TPSA ? Topological Polar Surface Area: Calculated from |
34.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.27 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.94 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.35 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.18 |
Solubility | 75.5 mg/ml ; 0.661 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.01 |
Solubility | 117.0 mg/ml ; 1.03 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.3 |
Solubility | 5.67 mg/ml ; 0.0497 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 |
-7.19 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 |
0.0 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) |
1.05 |
* 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 |
---|---|---|
81% | With toluene-4-sulfonic acid; In toluene; for 12h;Reflux; Inert atmosphere;Product distribution / selectivity; | 5-Bromo-2-(2,5-dimethyl-lH-pyrrol-l- l)-4,6-dimethylpyrimidine:; To a stirred solution containing 2.00 g (9.89 mmol) of 2-amino-5-bromo-4,6- dimethylpyrimidine in 16 mL of anhydrous toluene was added 1.36 mL (11.5 mmol) of 2,5- hexanedione followed by 96 mg (0.50 mmol) of /~-toluenesulfonic acid. The reaction mixture was heated and stirred at reflux for 12 h. The reaction mixture was poured into 150 mL of water and then extracted with 200 mL of ethyl acetate. The organic solution was washed with 150 mL of brine, dried (MgS04) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15 x 5 cm). Elution with 5: 1 hexanes-ethyl acetate afforded the expected product as light yellow crystals: yield 2.23 g (81%); mp 64-65 C; silica gel TLC Rf 0.65 (6: 1 hexanes-ethyl acetate); 1H NMR(CDC13) delta 2.34 (s, 6Eta), 2.67 (s, 6Eta) and 5.89 (s, 2H);13C NMR (CDC13) delta 14.5, 14.5, 24.9, 24.9, 108.7, 108.7, 118.6, 129.5, 129.5, 155.3, 155.3 and 166.9; mass spectrum (APCI), m/z 280.0458 (M+H)+ (Ci2Hi5N3Br requires 280.0449). |
81% | With toluene-4-sulfonic acid; In toluene; for 12h;Reflux; Inert atmosphere; | To a stirred solution containing 2.00 g (9.89 mmol) of <strong>[4214-57-7]2-amino-5-bromo-4,6-dimethylpyrimidine</strong> (5) in 16 mL of toluene was added 1.36 mL (1.32 g; 11.5 mmol) of 2,5-hexanedione followed by 96 mg (0.50 mmol) of p-toluenesulfonic acid. The reaction mixture was heated and stirred at reflux for 12 h. The reaction mixture was poured into 150 mL of water and then extracted with 200 mL of ethyl acetate. The organic solution was washed with 150 mL of brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15 * 5 cm). Elution with 5:1 hexanes/ethyl acetate afforded 6 as light yellow crystals: yield 2.23 g (81%); mp 64-65 C; silica gel TLC Rf 0.65 (6:1 hexanes/ethyl acetate); 1H NMR (CDCl3) delta 2.34 (s, 6H), 2.67 (s, 6H) and 5.89 (s, 2H); 13C NMR (CDCl3) delta 14.5, 24.9, 108.7, 118.6, 129.5, 155.3 and 166.9; mass spectrum (APCI), m/z 280.0458 (M+H)+ (C12H15N3Br requires 280.0449). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
platinum on carbon; In water; for 3h;Direct aqueous phase reforming; | Direct aqueous phase reforming (APR) experiments were conducted in 100-ml stirred reactors with draft-tube gas-induction impeller (Parr Series 4590). Reaction tests for direct bio-based feedstock aqueous phase reforming (APR) entailed filling the reactor with 60-grams of solvent (deionized water, or a mixture of DI water and isopropanol (IPA), and 3-3.5 grams of bio-based feedstock comprising biomass (bagasse, or pine sawdust)). One (1) gram of acetic acid was optionally charged to facilitate biomass hydrolysis.[0098] Bagasse was milled via a 1-mm grate. Dry, debarked Loblolly pine was ground via blender (Thomas Scientific of Swedesboro, NJ) and sieved to less than 30 mesh. Dry solids fraction was determined by vacuum drying at 80 °C to 82 °C. One gram of aqueous phase reforming catalyst (reduced 5percent Pt/C catalyst at 50percent moisture, or powdered 1.9percent Pt/A1203) was charged to the reactor, which was charged with 4200 kPa of hydrogen or nitrogen. To minimize degradation of hydrolysate to heavy ends, each reactor was typically heated with a staged temperature sequence of one hour at, 160 °C, 190 °C, 225 °C, and finally 250 °C, before leaving overnight at the final setpoint.[0099] Comparison tests were also conducted with glucose or sorbitol fed directly to the reaction in place of biomass, to simulate and quantify conversion of model hydrolysate to APR intermediates. Glucose is one of the sugars readily leached from biomass in hot water, while sorbitol is readily formed via hydrogenation of glucose, where platinum or other catalysts capable of hydrogenation are present.[00100] A batch reaction time of 20 hours under these conditions corresponds to a weight hourly space velocity (g-feed/g-catalyst/h) of about 3, for a comparable continuous flow reactor. A 0.5-micron sintered metal filter attached to a dip tube allowed liquid samples to be taken throughout the course of reaction, without loss of biomass or catalyst. Samples were analyzed by an HPLC method based on combined size and ion exclusionchromatography, to determine unreacted sorbitol, and amount of C3 and smaller polyols formed: glycerol (Gly), ethylene glycol (EG), and 1,2-propylene glycol (PG). Additional GC analysis via a moderate polarity DB-5 column were conducted to assess formation of C6 and lighter oxygenates (e.g., ketones, aldehydes, alcohols), as well as alkane and alkene products. A separate GC equipped with thermal conductivity and flame ionization (FID) detectors for refinery gas analysis, were used for detection of H2, C02, and light alkanes C1-C5. GC-mass spec was used to characterize select APR reaction product mixtures. Examples 1-3[00101] Batch APR reactions with sugar cane bagasse as biomass feed, and with a comparison of 25percent sorbitol as feed, were performed as described above. 1.7percent acetic acid was added to simulate catalysis of hydrolysis by recycle acid. Products formed from this concentration of acetic acid were subtracted from total product formation, to calculate the net production of liquid fuels from bagasse. This result shown in Table 1 shows the critical importance of concerted APR reaction with hydrolysis of biomass. In the absence of concerted aqueous phase reforming, the hydrolysate undergoes irreversible degradation (presumably to heavy ends), and cannot be reverted to liquid fuels upon subsequent APR and condensation. Converted reaction may be effected by direct inclusion of APR catalyst in the hydrolysis reactor, or via a pump around loop to recirculate liquid between a biomass contactor, and an APR catalytic reactor. Table 1: Direct APR of Biomass |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With acetic acid; at 100℃; for 4h; | A solution of 1 -phenyl-1 /-/-pyrazol-3-amine (3.5 g, 21 .9 mmol) in acetic acid (20 ml_) was treated with 2,5-hexadione (5.2 g, 45.9 mmol) and heated to 100 C for 4 h. The mixture was cooled and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using 5% EtOAc-hexanes eluent to give 3-(2,5-dimethyl-1 - -pyrrol-1 -yl)-1 -phenyl-1 H-pyrazole as a colorless liquid (2.8 g, 54%). 1 H NMR (400 MHz, CDCI3): delta = 7.98 (s, 1 H), 7.74 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.32 (t, J = 7.6 Hz, 1 H), 6.39 (s, 1 H), 5.9 (s, 2H), 2.19 (s, 6H). |
41.8 g | With acetic acid; for 3h;Reflux; | To a solution of <strong>[1128-56-9]1-phenyl-1H-pyrazol-3-ylamine</strong> (32.7 g) in acetic acid (330 ml) was added 2,5-hexanedione (25 ml), and the mixture was stirred for 3 hours at reflux. This reaction solution was cooled to room temperature, and then acetic acid was concentrated under reduced pressure, and then toluene (100 ml) was added thereto, and the mixture was further concentrated. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate 100/1 to 20/1) to give the titled compound (41.8 g). 1H-NMR (CDCl3) delta: 2.19 (s, 6H), 5.90 (s, 2H), 6.39 (d, 1H, J=2.4 Hz), 7.29-7.31 (m, 1H), 7.46-7.48 (m, 2H), 7.72-7.73 (m, 2H), 7.98 (d, 1H, J=2.4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.5 g | With sodium acetate; for 2.0h;Reflux; | To a solution of (2S)-3-chloro-2-hydroxypropylamine.HCl (14.6 g, 0.1 mol) ( prepared in Ex.1) and Sodium acetate ( 16.4 g, 0.2 mol) in acetic acid (150 ml) was added 2,5- hexanedione (12.54g, 0.1 1 mol) and then refluxed for 2 hrs. Pour the R.M into water (500 ml) and then extracted with DCM (100 ml x3 ). Washed DCM layer with sat. aq. Sodium bicarbonate solution ( 50 ml x 2) and water ( 50 ml x 2) . Distill- off the solvent under reduced pressure to yield title compound (Yield = 17.5 g, 92.2% of the theory). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.3% | With toluene-4-sulfonic acid; In toluene; for 2h;Inert atmosphere; Dean-Stark; Heating; | To a mixture of 6-chloropyrazin-2-amine (5 g, 38.6 mmol) and acetonylacetone (6.6 g, 57.9 mmol) in toluene (50 mL) was added p-toluenesulfonic acid (100 mg, 0.56 mmol) and the mixture was heated in a Dean-Stark apparatus for 2 hrs. The mixture was cooled to r.t. and diluted with EA (50 mL), washed with saturated aq.NaHCO3, brine successively, dried and concentrated to give a crude product, which was purified by chromatography (PE / EA = 20: 1) to give 2-chloro-6-(2,5-dimethyl-1H-pyrrol-1-yl)pyrazine (6.1 g, 77.3percent yield) as a yellow solid. Retention time (LC-MS): 1.503 min. MH+ 208. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.1% | With toluene-4-sulfonic acid; In toluene; at 110℃; for 17h;Inert atmosphere; Dean-Stark; | Step 2: Preparation of 5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl) nicotinonitrile (44) To a suspension solution of the intermediate 42 (90.0 g, 0.45 mol, 1.0 eq) in toluene (1.5 L) was added the compound 43 (78.2 g, 0.68 mol, 1.5 eq) and 4-methylbenzenesulfonic acid (2.5 g, 0.01 mol, 0.03 eq). The mixture was heated to 110 C. and stirred for 17 hours to remove water by Dean Stark trap. The mixture was cooled to room temperature, removed of toluene (about 1 L), and then added with EtOAc (2 L) and water (1 L). The mixture was filtered; the aqueous layer was extracted with EtOAc (2 L); the organic phase was washed with brine (3 L) and concentrated to give the crude product, which was purified by flash chromatography (EtOAc:Hexane=1:1) to give the intermediate 44 (110.0 g, 0.39 mol, 87.1%). 1H NMR (400 MHz, DMSO-d6) delta 9.07-9.06 (d, J=2.4 Hz, 1H), 8.96-8.95 (d, J=2.4 Hz, 1H), 5.88 (s, 2H), 2.01 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With acetic acid; In toluene; at 155℃; for 12h; | Hexane-2,5-dione (428.6 mg, 3.76 mmol) was added to a solution of <strong>[1010120-55-4]5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine</strong> (400 mg, 1.88 mmol) and acetic acid (215 muL) in toluene (5 mL). The mixture was stirred at 155 C. for 12 h. The mixture was concentrated to give a crude product. The crude product was purified by flash column chromatography over silica gel (eluent: petroleum ether/ethyl acetate from 100/0 to 40/60). The eluant was collected and the solvent was concentrated under reduced pressure to give 5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-[1,2,4]triazolo[1,5-a]pyridine as a yellow solid (500 mg, 91%). LC-MS: (ES, m/z): [M+1]+ 292.9 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In toluene; at 120℃;Inert atmosphere; Sealed tube; | A 50 mL vial with stir bar was charged with <strong>[56367-24-9]5-isopropyl-1H-pyrazol-3-amine</strong> (500 mg, 3.99 mmol, 1 .00 equiv.), 2,5-hexanedione (600 mg, 5.26 mmol, 1.32 equiv.) and toluene (10 mL, 0.4 M). AcOH (0.3 mL, 5.25 mmol, 1.31 equiv.) was added. The flask was evacuated and flushed with nitrogen. The vial was capped and placed in a 120C bath. The reaction mixture was stirred at 120C overnight. The next morning, the reaction mixture was cooled to room temperature. The reaction mixture was concentrated in vacuo. The resulting material was charged with H2O (50 mL). The mixture was extracted with DCM (3 x 50 mL), and the combined organic layers were washed with brine (2 x 40 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The resulting crude material was purified via silica gel chromatography to yield the desired product. |