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Chemical Structure| 39229-12-4

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Product Details of [ 39229-12-4 ]

CAS No. :39229-12-4
Formula : C14H9BrO2
M.W : 289.13
SMILES Code : O=C(C1=CC=C(Br)C=C1)C(C2=CC=CC=C2)=O
MDL No. :MFCD00223484
InChI Key :REKFALFAMJBFCR-UHFFFAOYSA-N
Pubchem ID :236701

Safety of [ 39229-12-4 ]

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

Computational Chemistry of [ 39229-12-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 69.25
TPSA ?

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

34.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.15
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

4.07
Log Po/w (WLOGP)?

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

3.51
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.

2.91
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

3.95
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.32

Water Solubility

Log S (ESOL):?

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

-4.52
Solubility 0.00871 mg/ml ; 0.0000301 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.49
Solubility 0.00932 mg/ml ; 0.0000322 mol/l
Class?

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

Moderately 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

-5.66
Solubility 0.000637 mg/ml ; 0.0000022 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

Yes
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

Yes
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.

-5.17 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

0.0
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.

1.0 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)

1.61

Application In Synthesis of [ 39229-12-4 ]

* 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 [ 39229-12-4 ]

[ 39229-12-4 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 13667-12-4 ]
  • [ 39229-12-4 ]
YieldReaction ConditionsOperation in experiment
90% With water; copper; Selectfluor; In acetonitrile; at 20℃; for 4h; General procedure: 1 or 3 (0.2 mmol), Cu(0) powder (0.64 mg, 5 mo%), Selectfluor (141.7 mg, 0.4 mmol, 2equiv), and CH3CN:H2O = 50:1 (V/V, 2 mL) were added to a 10-mL flask. Then the reaction mixture was stirred at room temperature for given times (see Table 2). Upon completion, the resulting mixture was diluted with CH2Cl2 (10 mL) and filtered through Celite. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel (100-200 mesh) using petroleum ether-EtOAc (20/1-3/1) as eluent to give pure 2 or 4.
83.9% With Oxone; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [Ru(cymene)Cl2]2; sodium hydrogencarbonate; In nitromethane; water; at 20℃; for 12h; General procedure: Alkyne (0.2 mmol), Oxone (330.0 mg), NaHCO3 (41.0 mg) were added to test tube. Nitromethane (4.0 mL) and water (0.5 mL) was added via syringe. A [Ru(cymene)Cl2]2 solution (10uL, 0.004 mM in distilled nitromethane, 0.02% equiv) and 3.12 mg TEMPO which were diluted by nitromethane were added into the tube. The reaction mixture was placed under air, stirred for 12h. And it must be noted that the mixture should be stirred vigorously. It was then quenched (consumption of residual Oxone) with saturated Na2SO3 solution and reaction mixture was extracted with ethyl acetate (3×4 mL). The organic layer was separated and dried with Na2SO4. Removal of solvent followed by flash column chromatographic purification afforded products.
82% With ammonium iodide; potassium ethyl xanthogenate; In water; dimethyl sulfoxide; at 130℃; for 12h;Schlenk technique; General procedure: A mixture of 1,2-diphenylethyne (1.0 mmol) and EtOCS2K (1.2 mmol) and NH4I (2.0 mmol) in 3 mL of DMSO/H2O (2:1) were stirred for 12 hours at 130 oC. Monitoring with TLC and GC-MS analysis was used to show the starting materials were completely consumed. After the reaction was finished, the reaction mixture was cooled to room temperature, the solution was filtered though a small amount of silica gel. The residue was purified by silica gel preparative TLC (n-hexane: EtOAc = 20:1), which furnished benzyl as a pale-yellow solid
82% With ammonium iodide; potassium ethyl xanthogenate; In water; dimethyl sulfoxide; at 130℃; for 12h; In the reaction tube, 128 mmg (0.51 mmol) of 1-bromo-4-(phenylethynyl)benzene was added, Potassium ethyl xanthate 96 mmg (0.60 mmol), ammonium iodide 145 mmg (1.00 mmol), dimethyl sulfoxide 2 mL, water 1 mL. The reaction was stirred at 130 C for 12 hours. At the end of the reaction, 10 mL of ethyl acetate was added to quench the reaction. After washing with 6 mL of saturated brine, the organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate (the amount of ethyl acetate was 6 mL). The organic phase was combined and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, The title product 1-(4-bromophenyl)-2-phenylethane-1,2-dione was isolated by column chromatography to give a yield of 82%.
72% With iodine; dimethyl sulfoxide; sodium sulfate; In ethanol; ethyl acetate; (ii) Synthesis of 1-(4-bromophenyl)-2-phenylethanedione A synthetic scheme of 1-(4-bromophenyl)-2-phenylethanedione is shown in (C-2). 10.0 g (38.9 mmol) of <strong>[13667-12-4](4-bromophenyl)phenylacetylene</strong>, 4.7 g (18.5 mmol) of iodine, and 100 mL of dimethyl sulfoxide were placed in a 300-mL three-neck flask, and the mixture was stirred at 155 C. for 4 hours. After the reaction, the reaction solution was cooled, then the reaction solution was put into a 1 wt % sodium sulfate aqueous solution. The precipitated solid was collected by suction filtration. The residue was dissolved into ethanol, and the insoluble part was filtered off through celite. The filtrate was concentrated, and the obtained solid was dissolved into ethyl acetate. The insoluble part was filtered off again by celite-filtration, and the filtrate was concentrated. A first recrystallization was performed on the obtained solid with ethyl acetate and hexane, giving 1.5 g of the target substrate as a solid. A second recrystallization was performed on the filtrate with acetone and hexane, giving 6.7 g of the target substrate as a solid. By the two-time recrystallization, 8.2 g of the product was obtained in the yield of 72%.
72% With iodine; at 155℃; for 4h; In the synthesis a (4-bromophenyl) phenylacetylene 10.0g (38.9mmol), iodine 4.7g (18.5mmol), dimethyl sulfoxide, and put into a 100mL three-necked 300mL flask was stirred for 4 hours at 155 . After the reaction, the reaction solution was cooled, then, one of theBy putting the reaction solution in the amount of% sodium sulfate aqueous solution, to precipitate a solid. After the precipitated solid collected by suction filtration, and the recovered filtrate was dissolved in water, ethanol, passed through Celite and filtered, and the filtrate was concentrated. The solid obtained was dissolved in ethyl acetate, it was passed again by Celite filtration, and the precipitated solid was filtered concentrated. The obtained solid to obtain a target product as a result of the solid was recrystallized from ethyl acetate-hexane 1.5g. Target substance added the filtrate obtained after the solid with acetone, the desired product as a result of the solid was recrystallized again from hexane to give 6.7g.Solid target compound obtained by two recrystallization is combined 8.2g, yield was 72%.
72% With [bis(acetoxy)iodo]benzene; toluene-4-sulfonic acid; In tetrahydrofuran; at 25℃; for 0.0833333h; The 0.3 mmol 1 - bromo -4 - (phenyl ethynyl) benzene, 0.6 mmol paratoluene sulfonic acid, 0.3 mmol iodobenzene diacetate is added to 15 ml thick-wall pressure in the reaction tube, add 3 ml tetrahydrofuran as the solvent. Then, for the 25 C under magnetic stirring 5 minutes. To be after the reaction is complete, the reaction liquid medicine spoon column to add two chromatography silica gel (100 - 200 mesh), and the solvent is removed by reduced pressure distillation, column chromatography separation through such as the structural formula shown in the pure product (petroleum ether/ethyl acetate=5:1 as the eluant). The material is a yellow solid, yield 72%.
71% With iodine; dimethyl sulfoxide; at 155℃; for 4h; A synthetic scheme of 1-(4-bromophenyl)-2-phenylethanedione is shown in (B-5). In a 300 mL three-necked flask were placed 7.4 g (28 mmol) of <strong>[13667-12-4](4-bromophenyl)phenylacetylene</strong>, 3.7 g (14 mmol) of iodine, and 70 mL of dimethyl sulfoxide. The solution was stirred at 155 C. for 4 hours under a stream of nitrogen. After a predetermined time, the solution was cooled to room temperature and added to about 200 mL of a 1 wt % aqueous sodium thiosulfate solution; then, a solid was precipitated. The solid was collected by suction filtration. The obtained solid was dissolved in ethyl acetate, and the solution was subjected to suction filtration through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855). The filtrate was condensed to obtain a solid. The obtained solid was recrystallized with ethyl acetate/hexane; thus, 4.5 g of target pale-yellow powder was obtained with a yield of 71%.
71% With iodine; dimethyl sulfoxide; at 155℃; for 4h; A synthetic scheme of 1-(4-bromophenyl)-2-phenylethanedione is shown in (A-2). In a 300 mL three-necked flask were placed 7.4 g (28 mmol) of <strong>[13667-12-4](4-bromophenyl)phenylacetylene</strong>, 3.7 g (14 mmol) of iodine, and 70 mL of dimethyl sulfoxide. The solution was stirred under nitrogen stream at 155 C for 4 hours. After a predetermined time, the solution was cooled to room temperature and added to a 1 wt% aqueous sodium thiosulfate solution; then, a solid was precipitated. The solid was collected by suction filtration. The obtained solid was dissolved in ethyl acetate, and the solution was subjected to suction filtration through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855). The filtrate was condensed to obtain a solid. The obtained solid was recrystallized with ethyl acetate/hexane; thus, 4.5 g of target pale-yellow powder was obtained with a yield of 71 %.
60% With magnesium bromide diethyl etherate; oxygen; In acetonitrile; for 24h;Irradiation; Typical procedure: A solution of diphenylacetylene (1, 0.3 mmol) and MgBr2·OEt2 (0.3 mmol) in dry MeCN (5 mL) in a pyrex test tube, purged with an O2-balloon, is stirred and irradiated externally with four 22 W fluorescent lamps, which are equipped in the distance of 65 mm, for 24 h. The reaction mixture is washed with aq. Na2S2O3 and brine, concentrated in vacuo, and purified by PTLC.
With iodine; dimethyl sulfoxide; sodium sulfate; In ethanol; ethyl acetate; (ii) Synthesis of 1-(4-bromophenyl)-2-phenylethanedione A synthesis scheme of 1-(4-bromophenyl)-2-phenylethanedione is shown in (B-2). Into a 300-mL three-neck flask were added 10.0 g (38.9 mmol) of <strong>[13667-12-4](4-bromophenyl)phenylacetylene</strong> synthesised by (i), 4.7 g (18.5 mmol) of iodine, and 100 mL of dimethyl sulfoxide, and the mixture was stirred at 155 C. for 4 hours. After the reaction, the reaction solution was cooled and then put into a 1 wt % sodium sulfate aqueous solution to precipitate a solid. The precipitated solid was collected by suction filtration. The collected residue was dissolved in ethanol, and then the solution was filtered through Celite. The filtrate was concentrated, and the obtained solid was dissolved in ethyl acetate. The solution was filtered again through Celite. The filtrate was concentrated to precipitate a solid. The obtained solid was recrystallized with ethyl acetate and hexane, giving 1.5 g of the target product as a solid. The filtrate from which the solid of the target product has been obtained was again recrystallized with acetone and hexane, giving 6.7 g of the target product as a solid. The total weight of the solid of the target product obtained by the two-time recrystallization was 8.2 g and the yield of the product was 72 %.

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Historical Records

Technical Information

• Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Clemmensen Reduction • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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