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Chemical Structure| 1131-62-0 Chemical Structure| 1131-62-0
Chemical Structure| 1131-62-0

1-(3,4-Dimethoxyphenyl)ethanone

CAS No.: 1131-62-0

4.5 *For Research Use Only !

Cat. No.: A265414 Purity: 98%

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Product Citations

Product Citations

Chapel Hill ;

Abstract: Photoredox catalysis has traditionally been accomplished by using ruthenium or iridium polypyridyl complexes. These complexes, while robust in their application, can prove to be quite cost prohibitive. Additionally, their respective redox windows are relatively narrow, limiting the scope of substrates with which they can undergo photoinduced electron transfer. Visible light absorbing organic chromophores have proven to be cost effective alternatives to precious transition metal photoredox catalysts. Additionally, the excited state redox potentials of organic photoredox catalysts can be significantly greater than that of their inorganic counterparts allowing for the development of new methodologies on substrates that could not otherwise undergo photoinduced electron transfer. In particular, organic acridinium dyes possess photophysical properties that make them extremely potent excited state oxidants. More recently it has been demonstrated that the acridine radical in the excited state possesses and excited state oxidation potential comparable to that of dissolving metal reductants making it an excellent excited state reductant. Herein, we describe methods developed that leverage the 5.51 V of redox potential that acridinium complexes can access. Nucleophilic aromatic substitution (SNAr) is a common method for arene functionalization; however, reactions of this type are typically limited to electron-deficient aromatic halides. Herein, we describe a mild, metal_x005f_x0002_free, cation-radical accelerated nucleophilic aromatic substitution (CRA-SNAr) using a potent acridinium photoredox catalyst as an excited state oxidant. Selective substitution of arene C−O bonds on a wide array of aryl ether substrates was shown with a variety of primary amine nucleophiles. Mechanistic evidence is also presented that supports the proposed CRA-SNAr pathway. Ketone–olefin coupling reactions are common methods for the formation of carbon–carbon bonds. This reaction class typically requires stoichiometric or super stoichiometric quantities of metal reductants and catalytic variations are limited in application. Photoredox catalysis has offered an alternative method towards ketone–olefin coupling reactions, although most methods are limited in scope to easily reducible aromatic carbonyl compounds. Herein, we describe a mild, metal-free ketone–olefin coupling reaction using an excited state acridine radical super reductant as a photoredox catalyst. We demonstrate both intra and intermolecular ketone–olefin couplings of aliphatic and aromatic ketones and aldehydes. Mechanistic evidence is also presented supporting an “olefin first”ketone–olefin coupling mechanism.

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Alternative Products

Product Details of [ 1131-62-0 ]

CAS No. :1131-62-0
Formula : C10H12O3
M.W : 180.20
SMILES Code : CC(C1=CC=C(OC)C(OC)=C1)=O
MDL No. :MFCD00008737
InChI Key :IQZLUWLMQNGTIW-UHFFFAOYSA-N
Pubchem ID :14328

Safety of [ 1131-62-0 ]

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

Calculated chemistry of [ 1131-62-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 49.62
TPSA ?

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

35.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.19
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

1.44
Log Po/w (WLOGP)?

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

1.91
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.

1.13
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

2.19
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.77

Water Solubility

Log S (ESOL):?

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

-2.01
Solubility 1.77 mg/ml ; 0.00982 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.

-1.79
Solubility 2.91 mg/ml ; 0.0162 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

-2.99
Solubility 0.186 mg/ml ; 0.00103 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

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.

-6.38 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)

1.5

Application In Synthesis [ 1131-62-0 ]

* 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 [ 1131-62-0 ]

[ 1131-62-0 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 50-00-0 ]
  • [ 51304-61-1 ]
  • [ 1131-62-0 ]
  • N-<1-(3,4-dimethoxyphenyl)propionyl>-4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine hydrochloride [ No CAS ]
  • 2
  • [ 91-16-7 ]
  • [ 108-24-7 ]
  • [ 38480-94-3 ]
  • [ 1131-62-0 ]
  • 3
  • [ 91-16-7 ]
  • [ 64-19-7 ]
  • [ 38480-94-3 ]
  • [ 1131-62-0 ]
  • 4
  • [ 91-16-7 ]
  • [ 141-78-6 ]
  • [ 38480-94-3 ]
  • [ 1131-62-0 ]
  • 5
  • [ 564443-27-2 ]
  • [ 1131-62-0 ]
  • [ 1257653-76-1 ]
YieldReaction ConditionsOperation in experiment
75% With sodium hydroxide; In ethanol; water; at 27℃; for 4.0h; Example 5(E)-l-(3,4-dimethoxyphenyl)-3-(6-(trifluoromethyl) imidazo [2,1- b] thiazol-5-yl)Prop-2-en-l-one (8f)To a stirred solution 3,4-dimethoxyphenyl acetophenone (180 mg, 2.7 mmol) and a 6- (trifluoromethyl) imidazo [2,1-b] thiazole-5-carbaldehyde (246 mg, 2.7 mmol) in ethanol (20ml) 10% aqueous solution of NaOH was added (5ml). The reaction mixture was stirred at room temperature 27C for 4 h and the reaction was monitored by TLC using ethyl acetate-hexane (3:7) as a solvent system. The solvent was evaporated under vacuum then the residue was dissolved in ethylacetate / water. The organic layer was washed with brine and evaporated. This was further purified by columnchromatography using ethyl acetate: hexane (2:8) as a solvent system to obtain the pure product (8f) as yellow solid (306 mg, 75% yield). Mp: 167-169 C'H NMR (CDC13, 300 MHz), delta 3.97 (s, 6H), 6.93 (d, 1H, J= 9.065 Hz), 7.19 (d, 1H, J = 4.53. Hz), 7.41 (d, 1H, J= 15.86 Hz ), 7.57 -7.61 (m, 2H), 7.83 (d, 1H, J= 4.53 Hz), 7.91 (d, 1H J= 15.86 Hz) , ESI-MS:382.35 (M+H)+.
  • 8
  • [ 17823-69-7 ]
  • [ 1131-62-0 ]
  • [ 1482517-93-0 ]
  • 10
  • [ 39974-94-2 ]
  • [ 1131-62-0 ]
  • C21H21NO4 [ No CAS ]
  • 11
  • [ 10102-94-0 ]
  • [ 1131-62-0 ]
  • C20H18BrNO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In ethanol; at 20℃; for 24h; General procedure: The relevant N-methyl intermediate (3a-c, 2 mmol), acetophenonederivate (2 mmol) and potassium hydroxide (6 mmol) wasdissolved in ethanol (20 mL) and stirred for 24 h. Then the reactionmixture was filtered and washed with water and cold ethanol. Thecrude product was purified by recrystallization from ethanol anddichloromethane to give pure chalcone (4a-q) with yields of34.2-93.1%.
  • 12
  • [ 16313-65-8 ]
  • [ 1131-62-0 ]
  • 2-(3,4-dimethoxybenzoyl)-6-nitro-4(3H)-quinazolinone [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With iodine; In dimethyl sulfoxide; at 20 - 110℃; for 2h; 2.3 g of 3,4-dimethoxyacetophenone was dissolved in 10 mL of DMSO.Slowly add 1.8g iodine,Drop at room temperatureAdd 2.3g<strong>[16313-65-8]<strong>[16313-65-8]2-Amino-5-nitrobenzamid</strong>e</strong> dissolved in 20mLa solution of DMSO,The reaction was carried out at 110 C for 2 h.150 mL of water was added to the reaction system.Extracted with (3 x 50 mL) ethyl acetate.Reuse (2 × 40mL)Washing with saturated NaHSO3 solution to remove iodine,After washing with water, dried over anhydrous magnesium sulfate.Evaporate the solvent under reduced pressure.The residue was separated by chromatography (eluent: ethyl acetate: petroleum ether = 1:2).2-(3,4-dimethoxybenzoyl)-6-nitro-4(3H)-quinazolinone 3.1 g,Yield 67%,
  • 13
  • [ 1131-62-0 ]
  • [ 204905-77-1 ]
  • (E)-3-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-one [ No CAS ]
  • 14
  • [ 10535-17-8 ]
  • [ 3929-47-3 ]
  • [ 90-05-1 ]
  • [ 1131-62-0 ]
  • 15
  • [ 10535-17-8 ]
  • [ 3929-47-3 ]
  • [ 5888-52-8 ]
  • [ 90-05-1 ]
  • [ 1131-62-0 ]
  • 16
  • [ 5147-80-8 ]
  • [ 1131-62-0 ]
  • (2Z,4E)‑2‑cyano‑3,5‑bis(methylsulfanyl)‑5‑(3,4‑dimethoxyphenyl)penta‑2,4‑dienoic acid amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With sodium hydroxide; In dimethyl sulfoxide; at 20℃; General procedure: To a solution of 3,3-bis(methylsulfanyl)methylenemalononitrile 1 (1.70 g, 10 mmol) in 20 mL of DMSO, keton 2a - j (10 mmol) and powdered sodium hydroxide (0.8 20 mmol) were added, and the mixture was magnetically stirred for 4 - 5 h at room temperature. After addition of 300 mL of water to the mixture, the solution was stirred for 12 h at room temperature. The formed precipitate was collected by filtra- tion and washed several times with water. After drying under air, the formed product was recrystallized using methanol or ethanol to obtain the pure products.
 

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