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Chemical Structure| 138642-62-3 Chemical Structure| 138642-62-3

Structure of 2-Cyanophenylboronic acid
CAS No.: 138642-62-3

Chemical Structure| 138642-62-3

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Product Details of [ 138642-62-3 ]

CAS No. :138642-62-3
Formula : C7H6BNO2
M.W : 146.94
SMILES Code : OB(C1=CC=CC=C1C#N)O
MDL No. :MFCD01632208
InChI Key :NPLZNDDFVCGRAG-UHFFFAOYSA-N
Pubchem ID :2734610

Safety of [ 138642-62-3 ]

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

Computational Chemistry of [ 138642-62-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 40.98
TPSA ?

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

64.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

0.54
Log Po/w (WLOGP)?

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

-0.76
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.

-0.36
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

-0.78
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.27

Water Solubility

Log S (ESOL):?

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

-1.43
Solubility 5.47 mg/ml ; 0.0373 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.

-1.46
Solubility 5.09 mg/ml ; 0.0346 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

-1.35
Solubility 6.52 mg/ml ; 0.0444 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

No
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

Yes
Log Kp (skin permeation)?

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

-6.81 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

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)

1.68

Application In Synthesis of [ 138642-62-3 ]

* 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 [ 138642-62-3 ]

[ 138642-62-3 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 138642-62-3 ]
  • [ 504-63-2 ]
  • [ 172732-52-4 ]
YieldReaction ConditionsOperation in experiment
82.4% at 20℃; for 1h; 3.69 g (48.5 mmol) of 1,3-propanediol was added to the organic phase obtained in Example 1, and the mixture was stirred at room temperature for 1 hour. After separation of the separated aqueous phase, the solvent was distilled off with an evaporator. 2 ml of toluene and 120 ml of heptane were added to the remaining oily matter to precipitate crystals. The obtained crystals were washed with 30 ml of heptane and then dried, 7.44 g (yield: 82.4percent) of 1,3-propanediol ester (2- (1,3,2-dioxaborinan-2-yl) benzonitrile) of 2-cyanophenylboronic acid was obtained. The crystal contained 0.40percent of 1-phenyl-1- (2,2,6,6-tetramethylpiperidin-1-yl) methylimine
57.2% In dichloromethane; Step 1: Synthesis of 2-(1,3,2-dioxaborinan-2-yl)benzonitrile 49.0 g (334 mmol) 2-cyanobenzeneboronic acid and 25.9 g (340 mmol) 1,3-propanediol were dissolved in 1 L CH2Cl2 with stirring in a 2 L round bottom flask for 20 h. The solution was then poured over a filter with suction to remove gummy solids. The filtrate was then dried with anhydrous MgSO4 to remove residual water, filtered and evaporated of solvent to give light-colored oil. The oil was then dissolved in CH2Cl2 and purified on a silica gel plug using CH2Cl2 as eluent. The product fractions were evaporated down to give the product as clear oil (35.7 g, 57.2percent yield).
57.2% In dichloromethane; for 20h; Step 1: Synthesis of 2-(1,3,2-dioxaborinan-2-yl)benzonitrile 49.0 g (334 mmol) 2-cyanobenzeneboronic acid and 25.9 g (340 mmol) 1,3-propanediol were dissolved in 1 L CH2Cl2 with stirring in a 2 L round bottom flask for 20 h. The solution was then poured over a filter with suction to remove gummy solids. The filtrate was then dried with anhydrous MgSO4 to remove residual water, filtered and evaporated of solvent to give light-colored oil. The oil was then dissolved in CH2Cl2 and purified on a silica gel plug using CH2Cl2 as eluent. The product fractions were evaporated down to give the product as clear oil (35.7 g, 57.2percent yield).
57.2% In dichloromethane; for 20h; Step 1: synthesis of 2-(1,3,2-dioxaborainan-2-yl)benzonitrile 49.0 g (334 mmol) 2-cyano-benzeneboronic acid and 25.9 g (340 mmol) 1,3-propanediol and stirred while 2 ? 1 ? round bottom flask in CH2Cl2 20 hours dongan was dissolved. Then, the solution was poured into a suction filter to remove the solids on the gum. Then, the filtrate was dried over anhydrous MgSO4 and removal of the residue, filtered, to give a lighter colored oil by evaporation of the solvent. Thereafter, the oil was dissolved in CH2Cl2, was purified using CH2Cl2 as eluent on a silica gel plug. Distilling the product fractions to obtain the product (35.7 g, 57.2percent yield) as a clear oil
20% In toluene; for 24h;Reflux; 2-cyano phenyl boronic acid and 1,3 propanediol was solubilized in anhydrous toluene. The reaction mixture was refluxed in a flask equipped with a Dean-Stark apparatus. After 24 h, the reaction was concentrated under reduced pressure to give colorless oil. The crude product was purified on silica gel (DCM) to give 2-[1-3]dioxaborinan-2-yl-benzonitrile; yield: 20percent; 1H NMR (300 MHz, CDCl3) delta ppm 2.08 (t, J = 5.4 Hz, 2H), 4.21 (q, J = 5.4 Hz, 4H), 5.31 (ls, 2H), 7.45 (td, J1 = 7.5 Hz, J2 = 1.5 Hz, 1H), 7.53 (td, J1 = 7.5 Hz, J2 = 1.5 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.85 (d, J = 7.5 Hz, 1H). The 2-[1-3]dioxaborinan-2-yl-benzonitrile was readily solubilized in toluene (0.2 M). To this solution, compound 3e (1eq), PdCl2(dppf) (2percent) and K3PO4 (2 eq) were added. The mixture was refluxed during 2 h, then was concentrated under reduced pressure. The obtained crude product was dissolved in ethyl acetate and washed by HCl 1N. The organic layer was concentrated under reduced pressure and purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (70/30) to give 9 as a yellow powder; purity 99percent; yield: 83percent; mp: 169-170 °C; 1H NMR (300 MHz, CDCl3) delta ppm 1.29 (t, J = 6.9 Hz, 3H), 2.10 (s, 3H), 4.23 (q, J = 6.9 Hz, 2H), 7.61 (td, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.69 (dd, J1 = 7.8 Hz, J2 = 0.9 Hz, 1H), 7.75 (d, J = 8.7 Hz, 2H), 7.82 (td, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.82 (dd, J1 = 7.8 Hz, J2 = 0.9 Hz, 1H), 7.82 (d, J = 8.7 Hz, 2H), 9.13 (s, 1H), 9.95 (sl, 1H); 13C NMR (75 MHz, CDCl3) delta ppm 15.0, 23.9, 60.8, 110.2, 110.9, 119.3, 119.5, 129.3, 130.1, 130.2, 132.7, 134.5, 134.8, 137.1, 139.6, 144.2, 148.4, 162.7, 169.6; LCMS (EI (+)) m/z = 389 [M + H] +. HRMS (EI) calcd for C21H18N4O2 [M + H]+ 375.14517. Found 375.14454.
In tetrahydrofuran; hexane; at 20℃; for 2h;Product distribution / selectivity; Example 3; The organic phase obtained in Example 2 was charged with 77 ml of 1,3-propanediol, and the resulting solution was stirred at room temperature for 2 hours. The free aqueous layer was separated, and then the solvent was removed by distillation using an evaporator. The residual oily substance was dissolved in 700 ml of dichloromethane, and the resulting solution was washed with 153 ml of water. The obtained organic phase was then dried with anhydrous magnesium sulfate, and turned into a solid by drying under reduced pressure using an evaporator. While stirring with a magnetic stirrer, 450 ml of hexane was slowly added dropwise to the oily residue under ice cooling to cause crystals to precipitate. The obtained crystals were washed with 500 of chilled hexane, and dried for 12 hours under reduced pressure at room temperature to obtain 184 g of the 1,3-propanediol ester of 2-cyanophenylboronic acid (2-(1,3,2-dioxaborinan-2-yl)benzonitrile). The purity was 99.4percent, and these crystals contained 0.45 mol percent of 1-phenyl-1-(2,2,6,6-tetramethylpiperidin-1-yl)methyl imine.
In tetrahydrofuran; Isopropyl acetate; toluene; at 20 - 25℃; for 2h; Example 2Synthesis of 2-(i ,3,2-dioxaborinane-2-yl)benzoni- trile?Effect of the Temperature in step a) on molaryield and chemical purity 10062] Into a previously dried flask, equipped with a thermometer, condenser and dropping thnnel, under nitrogen flow, 100.0 g (1.00 equiv.) of 2-bromobenzonitrile and 750 ml (7.5 V) of anhydrous Toluene are charged. The mixture is cooled at ?22/?18° C. and 519.0 g (1.30 equiv.) of Isopropylmagnesium chloride/lithium chloride complex 1.3 M (about 20percent wt/wt) in THF are added keeping the Tat ?22/?18° C., over about 1.5 h. The reaction is stirred at ?22/?18° C. for additional 4 hthen the conversion in checked by HPLC. When the reaction is complete, 125.6 g (2.20 equiv.) oftrimethylborate are added keeping the Tat ?22/?18° C. over about 0.5 h. Once the addition is complete, cooling is removed and the reaction is warmed to 20-25° C. and stirred for about 0.5 h. The conversion is checked by HPLC. When the reaction is complete, the mixture is cooled to 0-5°C. and a solution of 0.1 M hydrochloric acid, prepared by mixing 10 ml of 32percent hydrochloric acid (10.17 M) and 990 ml (9.9 V) of purified water, is added at 0-20° C. Afier stirring 0.25 h at 20-25° C. the pH is modified to 3-4 with appropriate amount of 32percent hydrochloric acid. The layers are then separated. The aqueous phase is extracted again with 500 ml (5 V) of Toluene. The organic phases are recombined and washed with 500 ml (5 V) of a saturated sodium chloride solution. The organic layer is extracted at 20-25° C. with 0.1 M sodium hydroxide solution, prepared by mixing 5 ml (0.05 V) of 30percent sodium hydroxide solution and 495 ml (4.95 V) of purified water (the product passes into the aqueous phase). Before performing layer separation the pH is modified to 10-11 with the appropriate amount of 30percent sodium hydroxide solution. Layers are separated and the organic layer is extracted twice with 0.1 M sodium hydroxide solution, prepared by mixing 5 ml (0.05 V) of 30percent sodium hydroxide solution and 495 ml (4.95 V) of purified water. The pH is corrected to 10-11 if needed before each layer separation. The aqueous phases are recombined and are washed with 2x300 ml (2x3 V) of Isopropyl acetate. The organic phase is discarded. The pH of the aqueous phase (containing the reaction product) is corrected with hydrochlonc acid to a final pH of 3-4. The aqueous phase is extracted with 2x500 ml (2x5 V) of Isopropyl acetate. The product passes into the organic phase. 46.0 g (1.1 equiv.) of 1,3- propanediol are then added to the organic solution and the mixture stirred at 20-25° C. for 2 h. The conversion in checked by TLC. When the reaction is complete, the aqueous phase is separated (water is generated during the reaction) and the organic layer is concentrated to residue at T bath 3 5-40° C. The residue is dissolved with 500 ml (5 V) of Dichloromethane and the organic phase is washed with 100 ml (1.0 V) of purified watet Layers are separated and the organic phase is concentrated to small volume in T bath 35-40°C. 100 ml (1.0 V) of n-Heptane are added keeping boiling under vacuum at T bath 35-40° C. and the mixture is concentrated to small volume. Then, 5 ml of Isopropanol and 300 ml (3.0 V) of n-Heptane are slowly added under vigorous stirring. The product crystallizes out. The slurry is stirred at 20-25° C. for 0.5 hand then at 0-5° C. for at least 2 h. The mixture is filtered and washed with 100 ml (1.0 V) of n-Heptane pre-cooled to 0-5° C. Afier vacuum drying at 20-25° C. for at least 8 h 75.1g of 2-(1,3,2-dioxaborinane-2-yl)benzonitrile equal to amolar yield from 2-bromo benzonitrile of 73percent. HPLC purity(AlA percent 99.9percent).

  • 2
  • [ 489446-42-6 ]
  • [ 138642-62-3 ]
  • [ 958-96-3 ]
  • tert-butyl ((3'-nitro-[1,1'-biphenyl]-4-yl)methyl)carbamate [ No CAS ]
  • 3
  • [ 1006-33-3 ]
  • [ 138642-62-3 ]
  • 2'-acetyl-4'-fluoro-[1,1'-biphenyl]-2-carbonitrile [ No CAS ]
  • 4
  • [ 935-99-9 ]
  • [ 138642-62-3 ]
  • 2'-acetyl-4'-chloro-[1,1'-biphenyl]-2-carbonitrile [ No CAS ]
 

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