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Structure of 92339-07-6

Chemical Structure| 92339-07-6

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Product Details of [ 92339-07-6 ]

CAS No. :92339-07-6
Formula : C8H6F4O2
M.W : 210.13
SMILES Code : OCC1=C(F)C(F)=C(CO)C(F)=C1F
MDL No. :MFCD00229147
InChI Key :SDHKGYDQOGCLQM-UHFFFAOYSA-N
Pubchem ID :4098835

Safety of [ 92339-07-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P233-P260-P261-P264-P271-P280-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501

Computational Chemistry of [ 92339-07-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 38.53
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

40.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.58
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.55
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.6
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.64
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.12

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.67
Solubility 4.45 mg/ml ; 0.0212 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-0.97
Solubility 22.4 mg/ml ; 0.107 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.18
Solubility 0.139 mg/ml ; 0.000659 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.19 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.48

Application In Synthesis of [ 92339-07-6 ]

* 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.

  • Downstream synthetic route of [ 92339-07-6 ]

[ 92339-07-6 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1897-41-2 ]
  • [ 92339-07-6 ]
  • 2
  • [ 92339-07-6 ]
  • [ 79538-03-7 ]
  • [ 703-87-7 ]
YieldReaction ConditionsOperation in experiment
82 - 88%Chromat.; 4 - 11%Chromat. With hydrogen;sponge cobalt catalyst in water-containing state; In toluene; at 160℃; under 3975.4 - 165017 Torr; for 0.5 - 1h;Product distribution / selectivity; To a 1 liter autoclave, 300 ml of toluene, 25 g of a sponge cobalt catalyst in a water-containing state (in which the catalyst amount is 5 g) and 30 g of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol were charged and a gas phase was thoroughly purged with hydrogen, and thereafter the hydrogen pressure was set to 1.5 MPa at ordinary temperature (the pressure means gauge pressure hereinafter). The stirring and heating for the autoclave were started and the temperature thereof was kept to 160 C. When the temperature reached to 160 C., the pressure was 2.2 MPa. The reaction was continued for 1 hr. Then, the autoclave was cooled to room temperature. After the cooling, the pressure showed 1.0 MPa. At this time, the amount of absorbed hydrogen was 104 mol % based on 2,3,5,6-tetrafluorobenzene-1,4-dimethanol charged. Hydrogen inside a reactor was removed, and thereafter the reaction mixture was recovered and the catalyst was filtered. [0059] The reaction mixture was heated under reduced pressure to remove the solvent by distillation, and further by gradually decreasing the pressure, a fraction distilled at 665 Pas at a temperature of from 100 to 105 C. was recovered. The fraction was analyzed with nuclear magnetic resonance spectrum (NMR) analysis and gas chromatography-mass spectroscopy (GC-MS) to identify 98% 2,3,5,6-tetrafluoro-4-methyl-benzyl alcohol. [0060] Further, using the distilled 2,3,5,6-tetrafluoro-4-methyl-benzyl alcohol as an authentic sample, a part of the reaction mixture recovered in the above reaction was analyzed with the gas chromatography internal standard method. In result, the conversion of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol was 94%, the yield of 2,3,5,6-tetrafluoro-4-methyl-benzyl alcohol was 88% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol), and the yield of 2,3,5,6-terafluoro-p-xylene was 4% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol).Example 5 [0068] To a 1 liter autoclave, 600 ml of toluene, 30 g of a sponge cobalt catalyst in a water-containing state (in which the catalyst amount is 6 g) and 60 g of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol were charged and gas phase was thoroughly purged with nitrogen. The stirring and heating for the autoclave were started and the temperature thereof was kept to 160 C. The pressure at this time was 0.28 MPa. Hydrogen was charged to the autoclave to increase the pressure to 0.53 MPa. Then, hydrogen was further fed to the autoclave to keep the pressure at 0.53 MPa, and when the hydrogen absorbing amount reached to 130 mol % based on 2,3,5,6-tetrafluorobenzene-1,4-dimethanol charged while watching the hydrogen flow rate, the reaction was stopped. The reaction required 30 minutes. [0069] Then, the autoclave was cooled to room temperature, gases inside the reactor were removed, and thereafter the reaction mixture was recovered and the catalyst was filtered. [0070] The resulting reaction mixture was analyzed with the gas chromatography internal standard method. In result, the conversion of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol was 99.5%, the yield of 2,3,5,6-tetrafluoro-4-methyl-benzyl alcohol was 82% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol), and the yield of 2,3,5,6-tetrafluoro-p-xylene was 11% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol).
58%Chromat.; 14%Chromat. With hydrogen;rhenium oxide-alumina catalyst; In 1,4-dioxane; at 220℃; under 36003.6 Torr; for 5h;Product distribution / selectivity; Example 4 To a 100 ml autoclave, 30 ml of 1,4-dioxane, 1.5 g of a supported rhenium oxide-alumina catalyst and 3.0 g of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol were charged and a gas phase was thoroughly purged with hydrogen, and thereafter the hydrogen pressure was set to 3 MPa at ordinary temperature.The stirring and heating for the autoclave were started and the temperature thereof was kept to 220 C. When the temperature reached to 220 C., the pressure was 4.8 MPa. The reaction continued for 5 hr. Then, the autoclave was cooled to room temperature and the pressure after the cooling showed 2.6 MPa. At this time, the amount of absorbed hydrogen was 116 mol % based on 2,3,5,6-tetrafluorobenzene-1,4-dimethanol charged.hydrogen inside a reactor was removed, and thereafter the reaction mixture was recovered and the catalyst was filtered.The resulting reaction mixture was analyzed with the gas chromatography internal standard method.In result, the conversion of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol was 83%, the yield of 2,3,5,6-tetrafluoro-4-methyl-benzyl alcohol was 58% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol), and the yield of 2,3,5,6-terafluoro-p-xylene was 14% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol).
40%Chromat.; 7%Chromat. With hydrogen;sponge cobalt catalyst in a water-containing state; In 1,4-dioxane; at 160℃; under 3750.38 Torr; for 4h;Product distribution / selectivity; Example 2 To a 100 ml autoclave, 30 ml of 1,4-dioxane, 2.5 g of a sponge cobalt catalyst in a water-containing state (in which the catalyst amount is 0.5 g) and 3.0 g of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol were charged and a gas phase was thoroughly purged with hydrogen, and thereafter the hydrogen pressure was set to 0.3 MPa at ordinary temperature.The stirring and heating for the autoclave were started and the temperature thereof was kept to 160 C. When the temperature reached to 160 C., the pressure was 0.5 MPa. hydrogen was fed to the autoclave to keep a pressure at 0.5 MPa, and when the hydrogen absorbing amount reached to 145 mol % based on 2,3,5,6-tetrafluorobenzene-1,4-dimethanol charged while watching the hydrogen flow rate, the reaction was stopped.The reaction required 4 hr. Then, the autoclave was cooled to room temperature.hydrogen inside a reactor was removed, and thereafter the reaction mixture was recovered and the catalyst was filtered. The resulting reaction mixture was analyzed with the gas chromatography internal standard method.In result, the conversion of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol was 69%, the yield of 2,3,5,6-tetrafluoro-4-methyl-benzyl alcohol was 40% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol), and the yield of 2,3,5,6-terafluoro-p-xylene was 7% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol).
37%Chromat.; 6%Chromat. With hydrogen;palladium on activated charcoal; In 1,4-dioxane; at 220℃; under 67506.8 Torr; for 12h;Product distribution / selectivity; Example 3 To a 100 ml autoclave, 30 ml of 1,4-dioxane, 3.0 g of a supported palladium-carbon catalyst and 3.0 g of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol were charged and a gas phase was thoroughly purged with hydrogen, and thereafter the hydrogen pressure was set to 5 MPa at ordinary temperature.The stirring and heating for the autoclave were started and the temperature thereof was kept to 220 C. When the temperature reached to 220 C., the pressure was 9 MPa. The reaction continued for 12 hr.Then, the autoclave was cooled to room temperature and the pressure after the cooling showed 4.7 MPa. At this time, the amount of absorbed hydrogen was 82 mol % based on 2,3,5,6-tetrafluorobenzene-1,4-dimethanol charged. hydrogen inside a reactor was removed, and thereafter the reaction mixture was recovered and the catalyst was filtered.The resulting reaction mixture was analyzed with the gas chromatography internal standard method.In result, the conversion of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol was 56%, the yield of 2,3,5,6-tetrafluoro-4-methyl-benzyl alcohol was 37% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol), and the yield of 2,3,5,6-terafluoro-p-xylene was 6% (on the basis of 2,3,5,6-tetrafluorobenzene-1,4-dimethanol).

  • 3
  • [ 3217-47-8 ]
  • [ 79538-03-7 ]
  • [ 703-87-7 ]
  • [ 92339-07-6 ]
YieldReaction ConditionsOperation 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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• Alkyl Halide Occurrence • Appel Reaction • Arndt-Eistert Homologation • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chugaev Reaction • Clemmensen Reduction • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Corey-Kim Oxidation • Dess-Martin Oxidation • Fischer Indole Synthesis • Friedel-Crafts Reaction • Grignard Reaction • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hunsdiecker-Borodin Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Jones Oxidation • Lawesson's Reagent • Leuckart-Wallach Reaction • Martin's Sulfurane Dehydrating Reagent • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mitsunobu Reaction • Moffatt Oxidation • Oxidation of Alcohols by DMSO • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Alcohols • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Preparation of Carboxylic Acids • Prins Reaction • Reactions of Alcohols • Reactions of Aldehydes and Ketones • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Carboxylic Acids • Reactions with Organometallic Reagents • Reformatsky Reaction • Ritter Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Sharpless Olefin Synthesis • Specialized Acylation Reagents-Ketenes • Stobbe Condensation • Swern Oxidation • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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