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Chemical Structure| 34036-07-2 Chemical Structure| 34036-07-2

Structure of 3,4-Difluorobenzaldehyde
CAS No.: 34036-07-2

Chemical Structure| 34036-07-2

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Product Details of [ 34036-07-2 ]

CAS No. :34036-07-2
Formula : C7H4F2O
M.W : 142.10
SMILES Code : C1=C(C=CC(=C1F)F)C=O
MDL No. :MFCD00010328
InChI Key :JPHKMYXKNKLNDF-UHFFFAOYSA-N
Pubchem ID :588088

Safety of [ 34036-07-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319-H335
Precautionary Statements:P210-P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P370+P378-P362+P364-P403+P233-P501

Computational Chemistry of [ 34036-07-2 ] 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.

1.41
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

1.88
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

2.21

Water Solubility

Log S (ESOL):?

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

-2.28
Solubility 0.74 mg/ml ; 0.00521 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.

-1.86
Solubility 1.96 mg/ml ; 0.0138 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.

-5.83 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)

1.03

Application In Synthesis of [ 34036-07-2 ]

* 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 [ 34036-07-2 ]

[ 34036-07-2 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 34036-07-2 ]
  • [ 3537-14-2 ]
  • [ 896114-98-0 ]
YieldReaction ConditionsOperation in experiment
In nitrobenzene; at 160℃; for 26h; 1.00 g 2,3-diamino-5-nitro-pyridine and 0.95 g 3,4-difluorobenzaldehyde were stirred in 60 ml nitrobenzene at 160 C for 26 hrs. The solvent was removed under vacuum and the residue dissolved in 40 ml pyridine at 60 C. The solution was cooled in an ice bath. Precipitated product was isolated by filtration and dried to yield 0.5 g of the title product.
In nitrobenzene; at 160℃; for 26h; Example 10-1 [2-(3,4-Difluoro-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-carbamic acid isopropyl ester a) 2-(3,4-Difluoro-phenyl)-6-nitro-3H-imidazo[4,5-b]pyridine; 1.00 g 2,3-diamino-5-nitro-pyridine and 0.95 g 3,4-difluorobenzaldehyde were stirred in 60 ml nitrobenzene at 160 C. for 26 hrs. The solvent was removed under vacuum and the residue dissolved in 40 ml pyridine at 60 C. The solution was cooled in an ice bath. Precipitated product was isolated by filtration and dried to yield 0.5 g of the title product.
  • 2
  • monohydrate of hydrazine [ No CAS ]
  • [ 28785-06-0 ]
  • [ 34036-07-2 ]
  • 1-(3,4-difluorobenzylidene)-2-(4-propylbenzylidene)hydrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; triethylamine; In ethanol; dichloromethane; (Example 4) Synthesis of 1-(3,4-difluorobenzylidene)-2-(4-propylbenzylidene)hydrazine (Compound No. 7 set forth in Table 1) To 40 g of a monohydrate of hydrazine was added a solution of 10 g of <strong>[28785-06-0]4-propylbenzaldehyde</strong> in 50 m of ethanol. The mixture was stirred at room temperature for 30 minutes. To the mixture was then added 150 m of saturated aqueous solution of sodium bicarbonate. To the mixture was then added 100 m of dichloromethane. The mixture was then washed with 150 m of saturated aqueous solution of sodium bicarbonate twice. To the resulting organic phase was then added 5 m of triethylamine. The mixture was then dehydrated and dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure. To the residue was then added 5 m of triethylamine. To the mixture were then added 50 m of ethanol and 8.5 g of 3,4-difluorobenzaldehyde. The mixture was then stirred at room temperature for 6.5 hours. To the mixture was then added 150 m of saturated aqueous solution of sodium bicarbonate. To the mixture was then added 100 m of dichloromethane. The mixture was then washed with 150 m of saturated aqueous solution of sodium bicarbonate twice. The solvent was then distilled off under reduced pressure. The residue was purified through alumina (basic) column chromatography (dichloromethane), and then recrystallized from methanol to obtain 5.7 g of 1-(3,4-difluorobenzylidene)-2-(4-propylbenzylidene)hydrazine. The compound thus obtained had a melting point of 50°C and exhibited nematic phase up to 59.5°C. The foregoing procedure was followed except that 4-methylbenzaldehyde, 4-ethylbenzaldehyde, 4-butylbenzaldehyde, 4-pentylbenzaldehyde, 4-heptylbenzaldehyde or 4-methoxybenzaldehyde was used instead of <strong>[28785-06-0]4-propylbenzaldehyde</strong>.
  • 3
  • [ 34036-07-2 ]
  • [ 120-35-4 ]
  • 3-(3,4-Difluoro-benzylamino)-4-methoxy-N-phenyl-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 274 3-(3,4-Difluoro-benzylamino)-4-methoxy-N-phenyl-benzamide The title compound has been made using the procedure of Example 50, but using 3-amino-4-methoxy-N-phenyl benzamide and 3,4-difluorobenzaldehyde as starting materials, which can be purchased from Aldrich; m.p. 150-152 C.
  • 4
  • [ 34036-07-2 ]
  • [ 1779-49-3 ]
  • [ 405-03-8 ]
YieldReaction ConditionsOperation in experiment
Methyltriphenylphosphonium bromide (251.31 g, 0.7037 mol), l,8-diazabicyclo[5.4.0]undec- 7-ene (117.84 g, 0.7741 mol) and toluene (250 ml) were taken into a clean and dry reaction assembly. The resulting mixture was heated at 40-45C, followed by stirring for 30 minutes. 3,4-Difluorobenzaldehyde (50 g, 0.3518 mol) was slowly added to the hot solution and the reaction mixture was heated at reflux temperature, followed by maintaining for 5 hours at reflux. After completion of the reaction, the mass was cooled to 25-30C, followed by washing with water (2 x 250 ml). The resulting mass was distilled under reduced pressure while maintaining the temperature at below 50C to give 3,4-difiuorostyrene.
Example 1 Preparation of 3,4-Difluorostyrene Methyltriphenylphosphonium bromide (71 g, 0.2111 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (35.37 g, 0.2311 mol) and toluene (75 ml) were taken into a clean and dry reaction assembly. The resulting mixture was heated at 40-45 C., followed by stirring for 30 minutes. 3,4-Difluorobenzaldehyde (15 g, 0.1055 mol) was slowly added to the above hot solution and the reaction mixture was heated at reflux temperature, followed by maintaining for 6 hours at reflux. After completion of the reaction, the mass was cooled to 25-30 C., followed by washing with water (2*250 ml). The resulting mass was distilled under reduced pressure while maintaining the temperature at below 50 C. to give 3,4-difluorostyrene.
General procedure: To a stirred suspension of methyltriphenylphosphonium bromide (1.61 g, 4.51 mmol, 1.5 equiv.)in 10 mL dry THF at -78 C under argon atmosphere, n-butyllithium (2.8 mL, 4.51 mmol, 1.6 Msolution in THF, 1.5 equiv.) was added dropwise. The yellow solution was allowed to stir for 15min. before addition of the 3,4 dimethoxybenzadehyde 5a (0.5 g, 3 mmol, 1 equiv.) in 5 mL dryTHF, upon which, the mixture turned white or pale yellow. After 2 h (or observed completion ofthe reaction by TLC), saturated ammonium chloride was added and the mixture extracted withCH2Cl2. The combined organic extracts were then dried (Na2SO4), and concentrated in vacuo. Evaporation of the solvent under reduced pressure gave the crude product. Purification by flashcolumn chromatography (Silica gel 230-400 mesh, 1-10% ethyl acetate/ petroleum ether)afforded the desired styrene 6a as a colorless liquid.
  • 5
  • [ 34036-07-2 ]
  • [ 31105-90-5 ]
  • 6
  • [ 40800-65-5 ]
  • [ 34036-07-2 ]
  • ethyl 4-[(3,4-difluorophenyl)methylidene]amino}-3-methylbenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% In ethanol; for 18h;Reflux; Step 1. Synthesis of ethyl 4-[(3,4-difluorophenyl)methylidene]amino}-3-methylbenzoate A solution of <strong>[40800-65-5]ethyl 4-amino-3-methylbenzoate</strong> (0.706 g, 3.94 mmol) and 3,4-difluorobenzaldehye (1.00 mL, 9.08 mmol) in ethanol (10 mL) was stirred at reflux for 18 h and cooled to room temperature. The crude was washed with diethyl ether/n-hexane (1:20) to give ethyl 4-[(3,4-difluorophenyl)methylidene]amino}-3-methylbenzoate (0.986 g, 83%) as an orange solid. 1H NMR (CDCl3, 400 MHz) delta 8.28 (s, 1H), 7.91-7.81 (m, 3H), 7.62-7.59 (m, 1H), 7.31-7.27 (m, 1H), 6.91 (d, 1H), 4.38 (q, 2H), 2.36 (s, 3H), 1.40 (t, 3H).
  • 7
  • [ 34036-07-2 ]
  • [ 1986-47-6 ]
  • (1S*,2R*)-N-(3,4-difluorobenzyl)-2-phenylcyclopropan-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% General procedure: Trans-2-phenylcyclopropylamine hydrochloride (1.0 eq.), acetic acid (1.0eq.) and the appropriate aldehyde (0.9 eq.) were dissolved in around bottom flask in 10 mL dry DCE. The reaction mixture was stirred gently at room temperature for 2 h before sodium triacetoxyborohydride (3.0 eq.) was added in small portions to the reaction vessel. The reaction was monitored by TLC and quenched using 10 mL of an aqueous (5%) NaHCO3 solution. The organic layer was separated and the aqueous layer extracted three times with10 mL of DCE. All organic layers were combined, dried over anhydrous Na2SO4, concentrated in vacuo and purified using flash chromatography (silica gel; cyclohexane/ethyl acetate) to give the desired compound.
  • 8
  • [ 34036-07-2 ]
  • [ 3537-14-2 ]
  • [ 896116-38-4 ]
 

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