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Chemical Structure| 1625-91-8

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Product Details of [ 1625-91-8 ]

CAS No. :1625-91-8
Formula : C20H26
M.W : 266.42
SMILES Code : CC(C1=CC=C(C2=CC=C(C(C)(C)C)C=C2)C=C1)(C)C
MDL No. :MFCD00008834
InChI Key :CDKCEZNPAYWORX-UHFFFAOYSA-N
Pubchem ID :74195

Safety of [ 1625-91-8 ]

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

Computational Chemistry of [ 1625-91-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 20
Num. arom. heavy atoms 12
Fraction Csp3 0.4
Num. rotatable bonds 3
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 90.42
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.89
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

7.7
Log Po/w (WLOGP)?

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

5.95
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.

6.77
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

6.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

6.08

Water Solubility

Log S (ESOL):?

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

-6.59
Solubility 0.0000687 mg/ml ; 0.000000258 mol/l
Class?

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

Poorly soluble
Log S (Ali)?

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

-7.54
Solubility 0.00000766 mg/ml ; 0.0000000287 mol/l
Class?

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

Poorly 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

-7.34
Solubility 0.0000123 mg/ml ; 0.0000000461 mol/l
Class?

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

Poorly soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
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

Yes
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

Yes
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.

-2.46 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

1.0
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

1.0
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)

1.92

Application In Synthesis of [ 1625-91-8 ]

* 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 [ 1625-91-8 ]

[ 1625-91-8 ] Synthesis Path-Downstream   1~35

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YieldReaction ConditionsOperation in experiment
With nitric acid; acetic anhydride; acetic acid; In dichloromethane; Preparation of 4,4'-di-tert-butyl-2-nitro-1,1'-biphenyl To <strong>[1625-91-8]4,4'-di-tert-butylbiphenyl</strong> (15.00 g, 56.30 mmol) was added acetic anhydride (300 mL) in a flask that was immersed in a room temperature water bath. To the suspension was added slowly dropwise a mixture of acetic acid (15 mL, 261.81 mmol) and fuming nitric acid (9.0 mL, 191.43 mmol) over the period of 10 minutes via a pressure equalizer addition funnel. The solid went into solution and turned yellow. The mixture was allowed to stir for 30 minutes and checked by GC/MS which showed reaction completion. The mixture was added to 2.5 L of ice-water and stirred for 1 hour 15 minutes. The yellow precipitate was collected by vacuum filtration and washed with two 100-mL portions of ice-water. This crude solid was dissolved in 250 mL of methylene chloride. The solution was washed with water (250 mL) and 1M aqueous NaOH (250 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under high vacuum to give the crude as a yellow solid. The crude solid was dissolved in minimum amount of chloroform for loading in the column cartridge.
  • 4
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  • [ 70728-89-1 ]
YieldReaction ConditionsOperation in experiment
98.6% With bromine; iodine; In dichloromethane; at 5 - 20℃; for 2h; EXAMPLE 1 1 g of <strong>[1625-91-8]4,4'-di-tert-butylbiphenyl</strong> were dissolved in 10 g of dichloromethane, and 30 mg of iodine were added. The mixture was then cooled to 5 C. Over a period of 1 h, 650 mg of bromine were added. The mixture was then stirred at room temperature for 1 h. For work-up, 3 ml of a 10% strength solution of NaHSO3 were added, the phases were separated and the organic phase was washed until neutral, dried and concentrated using a rotary evaporator. This gave 1.28 g of 2-bromo-<strong>[1625-91-8]4,4'-di-tert-butylbiphenyl</strong> (98.6% of theory).
91.5% With bromine; iodine; In dichloromethane; for 12h;Cooling with ice; In a 100 ml three-necked round bottom flask of adding 10g4, 4' - di-tert-butyl biphenyl (37.6mmol), proper amount of iodine simple substance, 15 ml dichloromethane, in ice water bath stirring for about 10min. At the same time added to the constant pressure dropping funnel in 5 ml dichloromethane and 2.3 ml bromine, in order to 2 seconds/drop in the speed of the bottle into the reaction, the reaction 12h after stop, will 30 ml saturated sodium sulfite solution is added in the reaction solution, stirring until the solution turns into yellow, then transferred to a separatory funnel in the solution, the violent oscillation, layered, collecting the lower organic matter, to the collected organic layer in adding anhydrous sodium sulfate drying, a certain time period, filtering, and steaming and removing the solvent in the filtrate, to obtain white crude product, in the crude product is added in proper amount of absolute ethanol, heating and stirring, reflux 30min, cooling at a standstill, with the white solid precipitated, filtered, anhydrous ethanol washing product, to obtain white solid, yield of 91.5%. Mp: 90 - 91 C
With bromine;iron(III) chloride; In chloroform; at 0℃; To a solution of 4,4'-di-tert-butylbirhohenyl (3.99 g, 15 mmol) and anhydrous ferric chloride (20 mg) in chloroform (30ml) at 0 C was added dropwise bromine (2.4 g, 15 mmol) solved in chloroform (10 ml). The reaction was stirred overnight The reaction mixture was quenched with sodum carbonate until the orange color disappeared. Then washed with water and extracted with hexane (50 ml) 3 times. The combined organic phase was washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo. 1HNMR measurement indicated tihat the conversion ratio is about 50%. The crude product was directly used for further reaction.
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YieldReaction ConditionsOperation in experiment
78% <strong>[1625-91-8]4,4'-di-tert-butylbiphenyl</strong> (1.5 g, 5.6 mmol) and iron powder (0.08 g) were added to dry CH2Cl2(40 mL). After cooling to 0 oC temperature, Br2 FontWeight="Bold" FontSize="10" (0.58 mL, 11.2 mmol) in CH2Cl2 (10 mL) was added dropwise. Kept the mixture at 0 oC temperature for 2 h, sodium bissulfite aqueous solution was added to quench Br2. The organic layer was separated, and dried over Na2SO4.After removal of the solvent, the crude product was chromatographically purified onsilica gel eluting with petroleum ether afford 2,2-dibromo-<strong>[1625-91-8]4,4'-di-tert-butylbiphenyl</strong> 8 (2.2 g, 78percent). 1H NMR (600 MHz, CDCl3, ppm): delta 7.68 (sd, 2H), 7.39(dd, J=6.0 Hz, 2H), 7.19 (d, J=6.0 Hz, 2H), 1.38 (s, 18H). 13CNMR (150 MHz, CDCl3, ppm): delta 152.71, 139.03, 130.74, 129.52, 124.16, 123.41, 34.72,31.23.
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YieldReaction ConditionsOperation in experiment
100% iron(III) chloride; In dichloromethane; at 20℃; To a stirred solution of biphenyl (15.4 g, 100 mmol) and anhydrous ferric chloride (80 mg) in dichlorometfaaiie (100ml) at room temperature was added slowly tert-butyl chloride (23.2 .ml, 21(5 mmol). The reaction was stirred overnight. The product was washed with water and extracted with hexane (100 ml) 3 times. The combined organic phase was washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo and gave 26.6 g of Compound S (yield 100%). 1H NMR (400 MHz, chloroform-d): delta, ppm 7.542 (d, 4 H), 7.444 (d, 4 H), 1.365 (s, 18 H).
85.7% With aluminum (III) chloride; In nitromethane; at 20℃; for 3h;Inert atmosphere; In 100 ml round bottom flask in three adding 8.0g (52mmol) biphenyl, 1.0g (7.5mmol) anhydrous aluminum chloride, vacuum, nitrogen, is added to the flask in 30 ml nitromethane, solid-dissolving, stirring continuously open at the same time circulating condensed water, then added to the constant pressure dropping funnel in 16 ml tert butyl chlorine, in order to 2 seconds/drop speed in is added to the bottle, after the completion of the reaction at room temperature 3h, after the reaction, the solution is purple, and a large number of solid produced in the bottle. By adding a small amount of water, the white solid precipitated, filtered, washing the filter cake with absolute ethanol, to obtain white solid, drying. The yield is 85.7%. Mp: 126 - 127 C.
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YieldReaction ConditionsOperation in experiment
83% With bis-triphenylphosphine-palladium(II) chloride; 1,1',1"-[benzene-1,3,5-triyltris(methylene)]tris[(octyl)-4-pyridin-4-ylpyridinium] hexafluorophosphate; tetrabutylammonium bis[(trifluoromethane)sulfonyl]imide; In N,N-dimethyl-formamide; at 60℃;Electrochemical reaction; General procedure: In an undivided cellequipped with a Zn sacrificial anode (1.5 x 1.0 cm2) and a Pt cathode (1.5 x 1.0 cm2) was placed a DMF(3 mL) solution of 4-bromopropiophenone (4a, 0.053 g, 0.25 mmol), 1 (0.14 g, 7.6 x 10-2 mmol),[Bu4N+][Tf2N-] (0.16 g, 0.30 mmol), and a catalytic amount of PdCl2(PPh3)2 (0.0086 g, 1.2 x 10-2 mmol).The solution was electrolyzed under constant current conditions (10 mA) at 60 C until 2 F/mol-4a ofelectricity was passed. The reaction mixture was poured into 5% aq. HCl (12 mL). The mixture wasextracted with AcOEt (10 mL x 3). The combined organic layer was washed successively with waterand brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified bycolumn chromatography (SiO2, toluene/AcOEt = 10/1) to afford 4,4?-dipropanoylbiphenyl (5a, 0.030 g,0.11 mmol, 89%).
68% With bis-triphenylphosphine-palladium(II) chloride; 1,1'-dioctyl-4,4'-bipyridinium bis(trifluimide); tetrabutylammonium bis[(trifluoromethane)sulfonyl]imide; In 1-methyl-pyrrolidin-2-one; at 60℃;Electrochemical reaction; A typical procedure of the electroreductive coupling of aryl bromide1 with catalytic amounts of [OctV2+][Tf2N]2 and Pd species isas follows. Into an undivided cell fitted with a Zn anode(1.5 1 cm2) and a Pt cathode (1.5 1 cm2) was added a DMF(3 mL) solution of 4-bromopropiophenone (1a, 0.25 mmol),[Bu4N+][Tf2N] (0.3 mmol), [OctV2+][Tf2N]2 (0.075 mmol,30 mol %), and PdCl2(PPh3)2 (0.0125 mmol, 5 mol %). The wholemixture was electrolyzed at 60 C under constant current(10 mA) conditions until 2 F/mol-1a of electricity was passed.The reaction mixture was poured into 5% aq HCl and extractedwith AcOEt. Purification by column chromatography (SiO2, toluene/AcOEt = 10/1) afforded 4,40-dipropanoylbiphenyl (2a) in 94%yield
64% With palladium diacetate; bis(tri-n-butyltin); cesium fluoride; tricyclohexylphosphine; In neat (no solvent); at 110℃; for 24h; A screw-cap vial equipped with a magnetic stir bar was charged with aryl halide (1 mmol), hexa-n-butylditin (0.5 mmol),palladium acetate (0.01 mmol) and tricyclohexylphosphine (0.02 mmol),followed by anhydrous cesium fluoride (1.5 mmol). The resulting mixture was manually homogenized with a magnet. A vial was transferred to a preheated oil bath (110 C). After 24 h, the mixture was cooled, dissolved in CH2Cl2-H2O mixture (1:1), the organic phase was separated, the solvent was evaporated in vacuo and the product was isolated by flash chromatography on a silica gel by elution with hexane-CH2Cl2 mixture.
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  • [ 61217-61-6 ]
YieldReaction ConditionsOperation in experiment
With lithium; In tetrahydrofuran; at 0℃;Inert atmosphere; Schlenk technique; Lithium ribbon (0.252 g, 36 mmol, 3 equiv), cut into small pieces, was introduced into a pre-dried Schlenk flask flushed with anhydrous argon. Anhydrous THF (40 mL) and 4,4?-di-tert-butylbiphenyl (DBB; 3.2 g, 12 mmol, 1 equiv) were sequentially added into the flask and the reaction mixture was stirred vigorously at 0 C. After 4-5 h, a deep-blue LiDBB solution in THF was obtained (ca. 0.25 M; determined by titration with a calibrated menthol solution in THF at 0 C until the blue color of LiDBB solution persisted).
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  • 2,7-di-tert-butyl-9,9-dimethyl-9H-9-silafluorene [ No CAS ]
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  • [ 4885-02-3 ]
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  • 2,7-di-tert-butyl-4-formyl-9-fluorenone [ No CAS ]
  • [ 189238-34-4 ]
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YieldReaction ConditionsOperation in experiment
41% Example 4 - Preparation of 4,4'-Di-t-butylbiphenyl. Into a 250 ml 3-neck round bottom flask equipped with a mechanical stirrer, thermometer, and inlet was charged, with agitation, 40 mL of nitromethane to which was added portionwise 20.7 grams (156 mmol, 1.69 eq) of aluminum chloride with agitation and cooling so as not to exceed 40° C. This solution was added to a mixture of 14.2 grams (92.1 mmol, 1.0 eq) of biphenyl and 26.5 grams (120 mmol, 1.3 eq) of 2,6-di-t-butyl-4-methylphenol in 40 mL of nitromethane at 15° C. over a period of 5 to 10 minutes. The mixture turned a dark opaque color and near the end of the addition, the mixture became very thick. The reaction mixture was allowed to stir for 30 minutes and then poured into ice-water. The mixture was extracted with ether twice and the ether layer was concentrated in vacuo. Additional ether was added to the solid and the mixture was concentrated in vacuo. Toluene was added to the solid and the mixture was concentrated in vacuo. This treatment was to insure removal of nitromethane before washing with base. The brown solid residue was dissolved in ether and washed with approximately 300 mL of 1M sodium hydroxide until the aqueous layer was no longer deeply colored. The organic layer was washed with water and concentrated in vacuo. The brown residue was recrystallized from approximately 150 mL of ethanol to give 10 grams (41percent yield). Melting point=129°-130° C.
 

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