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Chemical Structure| 437-81-0 Chemical Structure| 437-81-0

Structure of 2,6-Difluorobenzaldehyde
CAS No.: 437-81-0

Chemical Structure| 437-81-0

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Product Details of [ 437-81-0 ]

CAS No. :437-81-0
Formula : C7H4F2O
M.W : 142.10
SMILES Code : C1=CC=C(C(=C1F)C=O)F
MDL No. :MFCD00010293
InChI Key :SOWRUJSGHKNOKN-UHFFFAOYSA-N
Pubchem ID :136284

Safety of [ 437-81-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319-H335
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 437-81-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 31.75
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.37
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

1.58
Log Po/w (WLOGP)?

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

2.62
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.

2.32
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

2.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.14

Water Solubility

Log S (ESOL):?

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

-2.09
Solubility 1.14 mg/ml ; 0.00805 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-1.55
Solubility 4.01 mg/ml ; 0.0282 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

-2.88
Solubility 0.188 mg/ml ; 0.00132 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.

-6.05 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

2.0
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)

1.0

Application In Synthesis of [ 437-81-0 ]

* 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 [ 437-81-0 ]

[ 437-81-0 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 40230-24-8 ]
  • [ 437-81-0 ]
  • [ 68-11-1 ]
  • C25H17F2N3OS [ No CAS ]
  • 3
  • [ 437-81-0 ]
  • [ 2040-90-6 ]
  • [ 1268486-37-8 ]
  • 4
  • [ 437-81-0 ]
  • [ 1005-38-5 ]
  • [ 68-11-1 ]
  • [ 1350308-15-4 ]
YieldReaction ConditionsOperation in experiment
78.8% In toluene;Reflux; General procedure: The appropriate (hetero) aromatic amine (1.0 mmol) and 2',6'-/3',5'-dihalo-substituted (hetero/aromatic) aldehyde (1.5 mmol) were stirred in dry toluene under reflux condition followed by addition of mercaptoaceticacid (2.0 mmol). The reaction mixture was refluxed with a Dean-Stark trap for 24-48 h until the complete consumption of (hetero) aromatic amine. The reaction mixture was concentrated to dryness under reduced pressure and the residue was taken up in ethyl acetate. The organic layer was successively washed with 5percent aq citric acid, water, 5percent aq sodium hydrogen carbonate, and then finally with brine. The organic layer was dried over sodium sulfate and solvent was removed under reduced pressure to get a crude product that was purified by column chromatography on silica-gel (230-400 mesh) using hexane-ethyl acetate as eluent. The structures of synthesized compounds were characterized by means of TLC, IR, ESI-MS, 1H NMR, 13C NMR, elemental analyses and HRMS.
  • 5
  • [ 67-56-1 ]
  • [ 372-18-9 ]
  • [ 68-12-2 ]
  • [ 437-81-0 ]
  • [ 13671-00-6 ]
YieldReaction ConditionsOperation in experiment
10%; 58% General procedure: n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in THF (3 mL) at -78 C for 30 min. Then, DMF (0.22 mL, 2.2 mmol) was added to the mixture and the obtained mixture was stirred at rt. After 2 h at the same temperature, THF was removed. Then, MeOH (3 mL) was added to the residue and the mixture was stirred at room temperature. After 30 min, I2 (1523 mg, 6 mmol) and K2CO3 (829 mg, 6 mmol) were added at 0 C and the obtained mixture was stirred for 22 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3×20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide methyl 4-methoxy-1-benzoate in 82% yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure methyl 4-methoxybenzoate as a colorless oil.
  • 6
  • [ 67-56-1 ]
  • [ 437-81-0 ]
  • [ 13671-00-6 ]
  • 7
  • [ 437-81-0 ]
  • [ 13671-00-6 ]
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Arndt-Eistert Homologation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • Grignard Reaction • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hunsdiecker-Borodin Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Julia-Kocienski Olefination • Knoevenagel Condensation • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nozaki-Hiyama-Kishi Reaction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Preparation of Carboxylic Acids • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Carboxylic Acids • Reformatsky Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Stetter Reaction • Stobbe Condensation • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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