Home Cart Sign in  
Chemical Structure| 129931-47-1 Chemical Structure| 129931-47-1
Chemical Structure| 129931-47-1

3-Chloro-2-fluoro-5-(trifluoromethyl)benzonitrile

CAS No.: 129931-47-1

4.5 *For Research Use Only !

Cat. No.: A312194 Purity: 97%

Change View

Size Price

US Stock

Global Stock

In Stock
100mg łÿͶÊÊ Inquiry Inquiry
250mg łòò¶ÊÊ Inquiry Inquiry
1g łÇîó¶ÊÊ Inquiry Inquiry
5g łÿͧ¶ÊÊ Inquiry Inquiry

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 100mg

    łÿͶÊÊ

  • 250mg

    łòò¶ÊÊ

  • 1g

    łÇîó¶ÊÊ

  • 5g

    łÿͧ¶ÊÊ

In Stock

- +

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support Online Technical Q&A
Product Citations

Alternative Products

Product Details of [ 129931-47-1 ]

CAS No. :129931-47-1
Formula : C8H2ClF4N
M.W : 223.55
SMILES Code : N#CC1=CC(C(F)(F)F)=CC(Cl)=C1F
MDL No. :MFCD09999623
Boiling Point : No data available
InChI Key :XRFKGJGJYKZNMH-UHFFFAOYSA-N
Pubchem ID :19773824

Safety of [ 129931-47-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Calculated chemistry of [ 129931-47-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 41.13
TPSA ?

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

23.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.92
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

3.25
Log Po/w (WLOGP)?

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

4.94
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.

3.5
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

3.92
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.51

Water Solubility

Log S (ESOL):?

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

-3.52
Solubility 0.0668 mg/ml ; 0.000299 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.

-3.42
Solubility 0.0843 mg/ml ; 0.000377 mol/l
Class?

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

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

-4.27
Solubility 0.0119 mg/ml ; 0.0000533 mol/l
Class?

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

Moderately 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

Yes
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.

-5.36 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

1.0
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

0.0 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)

2.06

Application In Synthesis of [ 129931-47-1 ]

* 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 [ 129931-47-1 ]

[ 129931-47-1 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 129931-46-0 ]
  • [ 129931-47-1 ]
YieldReaction ConditionsOperation in experiment
71% With thionyl chloride; potassium carbonate; In N-methyl-acetamide; EXAMPLE III 3-Chloro-2-fluoro-5-(trifluoromethyl)benzonitrile was prepared as follows: Thionyl chloride, 6.0 g (50 mmol) was added to a slurry of 4.0 g (16 mmol) 3-chloro-2-fluoro-5-(trifluoromethyl) benzamide and 15 mL dimethylformamide at 0 C. After stirring for one hour the reaction mixture was diluted with 25 mL pentane and neutralized by dropwise addition of a saturated potassium carbonate solution and filtered. The pentane solution was dried and distilled to yield 3-chloro-2-fluoro-5-(trifluoromethyl) benzonitrile in 71% yield, bp 75-85 C./20 mm Hg.
  • 2
  • [ 129931-47-1 ]
  • [ 126538-80-5 ]
  • 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-4-pentafluoroethylpyrimidin-6-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
(c) 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-4-pentafluoroethylpyrimidin-6-one (compound No 4 in Table I) was prepared by the reaction of <strong>[129931-47-1]3-chloro-4-fluoro-5-cyano-trifluoromethylbenzene</strong> and 4-pentafluoroethylpyrimidin-6-one. 1 H NMR delta(CDCl3 /d6 -DMS0): 8.15 (1H,s); 8.09 (2H,m); 7.09 (1H,s).
  • 3
  • [ 126538-85-0 ]
  • [ 129931-47-1 ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; PREPARATION 2 This description illustrates the preparation of 3-chloro-4-fluoro-5-cyano-trifluoromethylbenzene. A solution of 3-amino-5-chloro-4-fluorotrifluoromethylbenzene (3g) in acetonitrile (10ml) was added dropwise to a stirred suspension of copper (I) cyanide (1.26g) in dry acetonitrile (50ml) whilst the reaction temperature was maintained at 0 C. After the addition was complete, the reaction mixture was allowed to warm to the ambient temperature (about 23 C.) and left overnight. The reaction mixture was poured into water, extracted with diethyl ether, dried over anhydrous magnesium sulphate and filtered. Evaporation of the solvent, under reduced pressure, gave a brown oil, which was flushed through a plug of silica gel using petroleum ether (boiling range 60-80 C.) containing diethyl ether (20% by volume) as eluent. After removal of the solvent, under reduced pressure, kugelrohr distillation of the residue gave two fractions, the first of which (boiling point 110 C. at 15mmHg) was predominantly composed of 3-chloro-4-fluoro-5-cyano-trifluoromethylbenzene. This material was used without further purification. 1 H NMR delta(CDCl3) 7.95 (1H, m); 7.85 (1H, m).
  • 4
  • [ 77227-95-3 ]
  • [ 129931-47-1 ]
YieldReaction ConditionsOperation in experiment
With potassium fluoride; In N-methyl-acetamide; toluene; PREPARATION 7 This description illustrates an alternate preparation of 3-chloro-4-fluoro-5-cyano-trifluoromethylbenzene. Dry potassium fluoride (1.94g) was added to a flask containing dry toluene (31 ml), dry dimethylformamide (7.8ml) and a catalytic amount of 18-crown-6. The stirred mixture was heated to reflux, and approximately 25 mls of the distillate was collected. After cooling to ambient temperature, 3-cyano-4,5-dichloro-trifluoromethylbenzene (4g) was added in one portion, and the stirred mixture was heated to 130 C. for 16 hours, and then to 145 C. for 24 hours. After cooling to ambient temperature, the reaction mixture was filtered, the residue washed with ethyl acetate, and the combined filtrate washed with brine. After drying over anhydrous magnesium sulphate, evaporation under reduced pressure gave a brown oil which was subjected to kugelrohr distillation, to give 3-chloro-4-fluoro-5-cyano-trifluoromethylbenzene as a pale yellow liquid (3.17g). 1 H NMR delta(CDCl3) 7.95 (1H,dq); 7.85 (1H,dq)
  • 5
  • [ 129931-47-1 ]
  • [ 124432-69-5 ]
  • 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-3-cyano-5-trifluoromethyl-2-pyridone [ No CAS ]
YieldReaction ConditionsOperation in experiment
(m) 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-3-cyano-5-trifluoromethyl-2-pyridone (Compound No 17 in Table II) was prepared by the reaction of <strong>[129931-47-1]3-chloro-4-fluoro-5-cyano-trifluoromethylbenzene</strong> and 3-cyano-5-trifluoromethyl-2-pyridone. 1 H NMR delta(CDCl13): 8.15 (2H,d); 8.05 (1H,d); 7.78 (1H,d)
  • 6
  • [ 129931-47-1 ]
  • [ 26387-78-0 ]
  • 1-(2-chloro-6-cyano-4-trifluoromethylphenyl)-3-dimethyl-aminopyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N-methyl-acetamide; mineral oil; Step (d) A solution of 3-dimethyl-aminopyrazole (440mg) in dimethylformamide (3ml) was added in small portions to a suspension of sodium hydride (160mg of a 60% suspension in mineral oil) in dimethylformamide (2ml). The reaction mixture was stirred until all effervescence had stopped and then it was added to a solution of 2-fluoro-3-chloro-5-trifluoromethylbenzonitrile (1g) in dimethylformamide (15ml) under a nitrogen atomsphere. After one hour of stirring the mixture was poured into brine and extracted with ethyl acetate. The extracts were washed with brine, dried over magnesium sulphate and the solvent evaporated under reduced pressure to give a yellow solid (910mg) which was purified by recrystallisation from hexane to give 1-(2-chloro-6-cyano-4-trifluoromethylphenyl)-3-dimethyl-aminopyrazole. melting point: 115-116 C. 1 H NMR delta(CDCl3): 7.94 (1H,d); 7.90 (1H,d); 7.86 (1H,d); 6.03 (1H,d); 2.98 (6H,s)
  • 7
  • [ 33252-64-1 ]
  • [ 129931-47-1 ]
  • 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-3-nitro-5-trifluoromethyl-2-pyridone [ No CAS ]
YieldReaction ConditionsOperation in experiment
(h) 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-3-nitro-5-trifluoromethyl-2-pyridone (Compound No 15 in Table II) was prepared by the reaction of 3-chloro-4-fluoro-5-cyanotrifluoromethylbenzene and 3-nitro-5-trifluoromethyl-2-pyridone. 1 H NMR delta(CDCl3): 8.65 (1H,d); 8.17 (1H,d); 8.08 (1H,d); 7.89 (1H,m).
  • 8
  • [ 129931-47-1 ]
  • 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-4-trifluoromethyl-2-pyridone [ No CAS ]
YieldReaction ConditionsOperation in experiment
(g) 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-4-trifluoromethyl-2-pyridone (Compound No 14 of Table II) was prepared by reacting 3-chloro-4-fluoro-5-cyanotrifluoromethylbenzene and 4-trifluoromethyl-2-pyridone. 1 H NMR delta(CDCl3) 8.10 (1H,d); 8.0 (1H,d); 7.26 (1H,dd); 7.04 (1H,s); 6.55 (1H,dd).
  • 9
  • [ 129931-47-1 ]
  • [ 109919-32-6 ]
  • 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-5-bromo-4-trifluoromethyl-2-pyridone [ No CAS ]
YieldReaction ConditionsOperation in experiment
(i) 1-(2-Chloro-6-cyano-4-trifluoromethylphenyl)-5-bromo-4-trifluoromethyl-2-pyridone (Compound No 16 in Table II) was prepared by the reaction of 3-chloro-4-fluoro-5-cyanotrifluoromethylbenzene and 5-bromo-4-trifluoromethyl-2-pyridone. 1 H NMR delta(CDCl3) 8.10 (1H,d); 8.01 (1H,d); 7.45 (1H,s); 7.13 (1H,s).
  • 10
  • [ 129931-47-1 ]
  • 5-(2-hydroxyisopropyl)-4-trifluoromethyl-pyrimidin-6-one [ No CAS ]
  • 1-(2-chloro-6-cyano-4-trifluoromethylphenyl)-5-(2-hydroxyisopropyl)-4-trifluoromethylpyrimidin-6-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage 1 1-(2-chloro-6-cyano-4-trifluoromethylphenyl)-5-(2-hydroxyisopropyl)-4-trifluoromethylpyrimidin-6-one was prepared from <strong>[129931-47-1]3-chloro-4-fluoro-5-cyano-trifluoromethylbenzene</strong> and 5-(2-hydroxyisopropyl)-4-trifluoromethyl-pyrimidin-6-one (Preparation 2) according to the general method disclosed in EP 0 398 499 for the preparation of Compound A1 in Table A1. Melting Point: 125.6 - 127.6C, 1H NMR delta(CDCl3): 8.14(s,1H); 8.05(s,1H); 7.99(s,1H); 3.45(s,1H); 1.75(d,6H).
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 129931-47-1 ]

Fluorinated Building Blocks

Chemical Structure| 94087-40-8

A263664 [94087-40-8]

3-Chloro-2-fluorobenzonitrile

Similarity: 0.89

Chemical Structure| 146780-26-9

A196817 [146780-26-9]

5-Chloro-2,4-difluorobenzonitrile

Similarity: 0.86

Chemical Structure| 887267-38-1

A141456 [887267-38-1]

3-Chloro-2,4-difluorobenzonitrile

Similarity: 0.85

Chemical Structure| 693245-52-2

A186260 [693245-52-2]

3-Chloro-5-(trifluoromethyl)benzonitrile

Similarity: 0.82

Chemical Structure| 57381-51-8

A116866 [57381-51-8]

4-Chloro-2-fluorobenzonitrile

Similarity: 0.81

Aryls

Chemical Structure| 94087-40-8

A263664 [94087-40-8]

3-Chloro-2-fluorobenzonitrile

Similarity: 0.89

Chemical Structure| 146780-26-9

A196817 [146780-26-9]

5-Chloro-2,4-difluorobenzonitrile

Similarity: 0.86

Chemical Structure| 887267-38-1

A141456 [887267-38-1]

3-Chloro-2,4-difluorobenzonitrile

Similarity: 0.85

Chemical Structure| 693245-52-2

A186260 [693245-52-2]

3-Chloro-5-(trifluoromethyl)benzonitrile

Similarity: 0.82

Chemical Structure| 57381-51-8

A116866 [57381-51-8]

4-Chloro-2-fluorobenzonitrile

Similarity: 0.81

Chlorides

Chemical Structure| 94087-40-8

A263664 [94087-40-8]

3-Chloro-2-fluorobenzonitrile

Similarity: 0.89

Chemical Structure| 146780-26-9

A196817 [146780-26-9]

5-Chloro-2,4-difluorobenzonitrile

Similarity: 0.86

Chemical Structure| 887267-38-1

A141456 [887267-38-1]

3-Chloro-2,4-difluorobenzonitrile

Similarity: 0.85

Chemical Structure| 693245-52-2

A186260 [693245-52-2]

3-Chloro-5-(trifluoromethyl)benzonitrile

Similarity: 0.82

Chemical Structure| 57381-51-8

A116866 [57381-51-8]

4-Chloro-2-fluorobenzonitrile

Similarity: 0.81

Nitriles

Chemical Structure| 94087-40-8

A263664 [94087-40-8]

3-Chloro-2-fluorobenzonitrile

Similarity: 0.89

Chemical Structure| 146780-26-9

A196817 [146780-26-9]

5-Chloro-2,4-difluorobenzonitrile

Similarity: 0.86

Chemical Structure| 887267-38-1

A141456 [887267-38-1]

3-Chloro-2,4-difluorobenzonitrile

Similarity: 0.85

Chemical Structure| 693245-52-2

A186260 [693245-52-2]

3-Chloro-5-(trifluoromethyl)benzonitrile

Similarity: 0.82

Chemical Structure| 57381-51-8

A116866 [57381-51-8]

4-Chloro-2-fluorobenzonitrile

Similarity: 0.81

Trifluoromethyls

Chemical Structure| 693245-52-2

A186260 [693245-52-2]

3-Chloro-5-(trifluoromethyl)benzonitrile

Similarity: 0.82

Chemical Structure| 32137-20-5

A536246 [32137-20-5]

1-Chloro-2-fluoro-4-(trifluoromethyl)benzene

Similarity: 0.81

Chemical Structure| 1092460-79-1

A146970 [1092460-79-1]

3-Chloro-4-(trifluoromethyl)benzonitrile

Similarity: 0.78

Chemical Structure| 328-87-0

A210386 [328-87-0]

2-Chloro-5-trifluoromethylbenzonitrile

Similarity: 0.78

Chemical Structure| 1813-33-8

A247204 [1813-33-8]

2-Chloro-4-(trifluoromethyl)benzonitrile

Similarity: 0.77