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Chemical Structure| 613-46-7 Chemical Structure| 613-46-7

Structure of 2-Naphthonitrile
CAS No.: 613-46-7

Chemical Structure| 613-46-7

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Product Details of [ 613-46-7 ]

CAS No. :613-46-7
Formula : C11H7N
M.W : 153.18
SMILES Code : N#CC1=CC=C2C=CC=CC2=C1
MDL No. :MFCD00016807
InChI Key :AZKDTTQQTKDXLH-UHFFFAOYSA-N
Pubchem ID :11944

Safety of [ 613-46-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 613-46-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 48.66
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.

1.97
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

2.68
Log Po/w (WLOGP)?

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

2.71
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.

2.48
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

2.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.56

Water Solubility

Log S (ESOL):?

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

-3.09
Solubility 0.123 mg/ml ; 0.000804 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.

-2.83
Solubility 0.226 mg/ml ; 0.00147 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

-4.14
Solubility 0.011 mg/ml ; 0.0000721 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.

-5.33 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

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)

1.28

Application In Synthesis of [ 613-46-7 ]

* 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 [ 613-46-7 ]

[ 613-46-7 ] Synthesis Path-Downstream   1~20

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YieldReaction ConditionsOperation in experiment
88% General procedure: A flame-dried resealable 2-5 mL Pyrex reaction vessel was charged with the solid reactant(s): (hetero)aryl nitriles 1 (1.0 mmol) and Cs2CO3 (1.5 mmol). The reaction vessel was capped with a rubber septum, and pyrrolidinone (2 mL per mmol [0.5 M]) was added through the septum. The septum was replaced with a teflon screwcap. The reaction vessel was sealed and heated at 130 °C for 2 h. The resulting suspension was cooled to room temperature and filtered through a pad of celite eluting with CH2Cl2/MeOH (7:3), and the inorganic salts were removed. The filtrate was concentrated and purification of the residue by silica gel column chromatography gave the desired product.
88% With water; at 110℃; for 6h; General procedure: Two milli liter water at room temperature was added to astirred mixture of nitrile (1mmol) and catalyst (40mg) thenheated with an oil bath maintained at 110°C, and stirred. After completion of the reaction (monitored by TLC), thecatalyst was removed from the reaction mixture by externalmagnet. Then the mixture was extracted with ethyl acetate,subsequently purified by column chromatography on silicagel to provide the corresponding amide products.
70%Chromat. With [Ru(CO)(pyridoxal-4-methyl-thiosemicarbazide hydrochloride)(triphenylphosphine)2]; In methanol; water; at 80℃; for 1h;Catalytic behavior; General procedure: Organic nitrile (1 mmol) and distilled water (1 mL) were sequentially added to 3 mL methanol solution of the ruthenium catalyst (0.3 molpercent) and the reaction mixture was stirred at 80°C. After completion of reaction, the catalyst was extracted from the reaction mixture by the addition of CH2Cl2/petroleum ether followed by filtration. The filtrate was subjected to GC analysis and the product was identified and determined with authentic samples
With C40H45ClN3O2PRu; In methanol; water; at 20℃; for 4h;Inert atmosphere; Schlenk technique; Green chemistry;Catalytic behavior; General procedure: Organic nitrile (1 mmol) and distilled water (1 mL) were sequentially added to 3 mL methanol solution of the [Ru?NHC] catalyst (0.5 molpercent) and the reaction mixture was stirred at room temperature. The progress of the reaction in each case was monitored by TLC analysis. After completion of reaction the catalyst was extracted from the reaction mixture by the addition of CH2Cl2/petroleum ether followed by filtration. The filtrate was subjected to GC analysis and the product was identified with authentic samples.

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YieldReaction ConditionsOperation in experiment
96% With oxalyl dichloride; triethylamine; In dimethyl sulfoxide; acetonitrile; at 20℃; for 0.666667h;Inert atmosphere; Nitrogen protection, in a 100 mL three-necked flask equipped with a thermometer,Add anhydrous acetonitrile (10 mL) in turn, twoJia Ya satire (0·03mmol, 2·5mg, 0·Olequiv),2-naphthylcarboxamide (3mmol, 513mg, 1 · Oequiv)And triethylamine (1 · 04mL, 7 · 5mmol, 2 · 5equiv),Slowly add oxalyl chloride to the constant pressure dropping funnel at room temperature(0.31 mL, 3.6 mmol, 1.2 equiv) in dry acetonitrile (5 mL).After the addition was completed, stirring was continued for 40 min, suction filtration, and the filtrate was spun dry.Distilled water (15 mL) was added and extracted with ethyl acetate (3 chi 10 mL).The combined organic layers were washed with aq.Filtration, rotary distillation to remove the solvent to obtain a crude product.Purified by column chromatography (petroleum ether / ethyl acetate = 9:1),441 mg of 2-naphthonitrile was obtained in a yield of 96%.
84% at 300℃; for 1h; General procedure: Following the amide intermediate Preparation Example A. The reaction vessel is closed (when the amide intermediate has a boiling point at normal pressure equal to or lower than the reaction temperature TB described below) or the reaction vessel is kept open (when the amide intermediate has a boiling point higher than the normal pressure When the reaction temperature is TB), the stirring is continued (600 r/min), the reaction temperature is changed to TB, and after the reaction temperature TB is maintained for TD hours, the reaction is almost complete. Then, the reaction vessel was sealed and connected to a vacuum pump so that the degree of vacuum in the reaction vessel reached 20-50 mbar (according to the type of nitrile product) and the distillate was used as the nitrile product. The yield of the nitrile product was calculated and sampled for nuclear magnetic proteomics and elemental analysis to characterize the nitrile product obtained. Specific reaction conditions and characterization results are shown in Tables A-7, A-8, A-9, A-10 and A-11 below. These characterization results show that the nitrile product obtained has an extremely high purity (above 99%).In these nitrile product preparation examples, 10 g of diphosphorus pentoxide was optionally added to the reaction vessel as a catalyst at the start of the reaction.
61% With triethylamine; ethanaminium,N-(difluoro-lambda4-sulfanylidene)-N-ethyl-,tetrafluoroborate; In toluene; at 20℃; for 4h;Inert atmosphere; General procedure: To a solution of the aldoxime or the amide (1.0 mmol) and Et3N (1.5mmol) in EtOAc (1 mL, 1 M) at r.t. was added XtalFluor-E8 (1.1 mmol)portionwise over ca. 2 min. The resulting solution was stirred at r.t.for 1 h. The reaction mixture was quenched with sat. aq Na2CO3 and extracted with CH2Cl2 (2 × 10 mL). The combined organic layers were washed with H2O and brine, dried (MgSO4), and concentrated under vacuum to afford the crude nitrile, which was purified by flash chromatography, if required.
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  • alkali [ No CAS ]
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  • cyanides [ No CAS ]
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  • potassium ferro cyanide [ No CAS ]
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  • sodium [ No CAS ]
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YieldReaction ConditionsOperation in experiment
With 10% CuO-ZnO on activated carbon; In toluene; at 100℃; for 4h;Inert atmosphere; General procedure: Calculated amount of catalyst (for example 60 mg), benzaldehyde oxime 4 (670 mg) and 1.1 mL toluene as a solvent were taken in an oven-dried, nitrogen purged Schlenk tube. Then the mixture was purged with nitrogen and stirred at 100 °C for 4 h. After set reaction time, the mixture was allowed to cool to room temperature, diluted with 2 mL ethanol, and filtered. The analysis of filtered reaction mixture was carried out by gas chromatography (Varian 3900) equipped with CP-Sil 5CB capillary column (15 m length and 0.25 mm diameter) and a flame ionization detector (FID). GC oven temperature was programmed from 60 to 110 °C at the rate of 8 °C/min and 111 to 300 °C at the rate of 25 °C/min. Helium was used as a carrier gas. Temperatures of injection port and FID were kept constant at 295 and 300 °C, respectively. Retention times of different compounds were determined by injecting pure compound under identical conditions.
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  • C46H54Fe2N2S2(2+)*F6P(1-)*BF4(1-) [ No CAS ]
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