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Structure of 103426-20-6

Chemical Structure| 103426-20-6

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Product Details of [ 103426-20-6 ]

CAS No. :103426-20-6
Formula : C8H7ClO
M.W : 154.59
SMILES Code : O=CC1=CC(C)=CC(Cl)=C1
MDL No. :MFCD11553565

Safety of [ 103426-20-6 ]

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

Computational Chemistry of [ 103426-20-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 41.81
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.85
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

2.82
Log Po/w (WLOGP)?

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

2.46
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.

2.37
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

3.08
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.52

Water Solubility

Log S (ESOL):?

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

-2.95
Solubility 0.172 mg/ml ; 0.00111 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.

-2.84
Solubility 0.226 mg/ml ; 0.00146 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

-3.33
Solubility 0.0718 mg/ml ; 0.000465 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.

-5.24 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

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)

1.05

Application In Synthesis of [ 103426-20-6 ]

* 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 [ 103426-20-6 ]

[ 103426-20-6 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 103426-20-6 ]
  • [ 189161-09-9 ]
  • 2
  • [ 103426-20-6 ]
  • 3-Chloro-N-(4-methanesulfonyl-phenyl)-5-methyl-benzamidine [ No CAS ]
  • 3
  • [ 103426-20-6 ]
  • [ 177661-46-0 ]
  • 4
  • [ 103426-20-6 ]
  • [ 177661-14-2 ]
  • 5
  • [ 103426-20-6 ]
  • [ 1027488-95-4 ]
  • 6
  • [ 79-46-9 ]
  • [ 556-97-8 ]
  • [ 62358-81-0 ]
  • [ 67-68-5 ]
  • [ 103426-20-6 ]
  • [ 56961-33-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; sodium hydroxide; N-Bromosuccinimide; potassium tert-butylate; silver nitrate; dibenzoyl peroxide; In tetrachloromethane; water; 3-Chloro-5-methylbenzoic acid A well stirred mixture of N-bromosuccinimide (32.5 g), 5-chloro-m-xylene (25.6 g) and carbon tetrachloride (500 ml) is refluxed for 8 hours. The solution is well illuminated and every 2 hours small quantities of benzoyl peroxide are added. The cooled mixture is filtered and the solvent evaporated to give an oil consisting of a mixture of 3-chloro-5-methylbenzyl bromide and 5-chloro-m-xylene in a ratio of about 2:1 (34.5 g). The above mixture is added to a stirred mixture of potassium tert-butoxide (14 g), 2-nitropropane (11 g) and dimethylsulphoxide (100 ml) and the mixture is stirred overnight at room temperature. Water (500 ml) is added and the separated oil extracted with ether. Evaporation of the dried ether solution yields an oil consisting of a mixture of <strong>[103426-20-6]3-chloro-5-methyl-benzaldehyde</strong> and 5-chloro-m-xylene (approximately 1:1) (18.5 g). The above mixture is slowly added over a 15 minute period to a stirred suspension of moist silver oxide [prepared from silver nitrate (24 g) and an aqueous solution of sodium hydroxide (5.7 g)] in a solution of sodium hydroxide (5.7 g) in water (50 ml). The stirred mixture is refluxed for 30 minutes, cooled, filtered and the filtrate extracted with ether. Acidification of the aqueous layer with 2N HCl yields a precipitate which is filtered and recrystallized from aqueous methanol to yield 3-chloro-5-methylbenzoic acid, 174-175 C. (9.4 g).
With hydrogenchloride; sodium hydroxide; N-Bromosuccinimide; potassium tert-butylate; silver nitrate; dibenzoyl peroxide; In tetrachloromethane; water; 3-Chloro-5-methylbenzoic acid A well stirred mixture of N-bromosuccinimide (32.5 g), 5-chloro-m-xylene (25.6 g) and carbon tetrachloride (500 ml) is reflexed for 8 hours. The solution is well illuminated and every 2 hours small quantities of benzoyl peroxide are added. The cooled mixture is filtered and the solvent evaporated to give an oil consisting of a mixture of 3-chloro-5-methyl-benzyl bromide and 5-chloro-m-xylene in a ratio of about 2:1 (34.5 g). The above mixture is added to a stirred mixture of potassium tert-butoxide (14 g), 2-nitropropane (11 g) and dimethylsulphoxide (100 ml) and the mixture is stirred overnight at room temperature. Water (500 ml) is added and the separated oil extracted with ether. Evaporation of the dried ether solution yields an oil consisting of a mixture of <strong>[103426-20-6]3-chloro-5-methyl-benzaldehyde</strong> and 5-chloro-m-xylene (approximately 1:1) (18.5 g). The above mixture is slowly added over a 15 minute period to a stirred suspension of moist silver oxide [prepared from silver nitrate (24 g) and an aqueous solution of sodium hydroxide (5.7 g)] in a solution of sodium hydroxide (5.7 g) in water (50 ml). The stirred mixture is refluxed for 30 minutes, cooled, filtered and the filtrate extracted with ether. Acidification of the aqueous layer with 2N HCl yields a precipitate which is filtered and recrystallized from aqueous methanol to yield 3-chloro-5-methylbenzoic acid, 174-5 C. (9.4 g).
  • 7
  • methanolic KOH [ No CAS ]
  • [ 75-09-2 ]
  • [ 103426-20-6 ]
  • 3-Chloro-5-methylphenyl-(trichloromethyl)carbinol [ No CAS ]
  • [ 115-20-8 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In chloroform; N,N-dimethyl-formamide; EXAMPLE 12 3-Chloro-5-methylphenyl-(trichloromethyl)carbinol A cold solution (-10 C.) of <strong>[103426-20-6]3-chloro-5-methylbenzaldehyde</strong> (19.5 g) and chloroform (15.6 ml) in 76 ml of DMF was treated dropwise with a 5M methanolic KOH solution (17.16 ml). The reaction mixture was stirred for 2 hours at -10 C. and then poured into a cold mixture of 170 ml of 1N HCl and 170 ml of CH2 Cl2 with vigorous stirring. The layers were separated and the aqueous phase further extracted with CH2 Cl2 (2*200 ml). The combined organic layers were washed with water (3*100 ml) and then dried over MgSO4. Concentration produced 38.17 g of a crude oil. Purification by silica gel chromatography with 50:50 hexane:CH2 Cl2 as eluent gave 32.3 g of pure trichloromethyl carbinol.
  • 8
  • (3-chloro-5-methylphenyl)methanol [ No CAS ]
  • [ 79-37-8 ]
  • [ 103426-20-6 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; EXAMPLE 11 3-Chloro-5-methylbenzaldehyde To a cold solution (-60 C.) of oxalyl chloride (14.88 ml) in 300 ml of CH2 Cl2, dimethylsulfoxide (25.16 ml) in 75 ml of CH2 Cl2 was added followed by the addition of 3-chloro-5-methylbenzyl alcohol (23 g) in 100 ml of CH2 Cl2. To this cold mixture, triethylamine (103 ml) was slowly added (exothermic) over 20 minutes. The reaction mixture was then permitted to warm to room temperature over 1.5 hours. The mixture was then added to 1 L of water and the layers separated. The CH2 Cl2 layer was repeatedly washed with water and then dried with MgSO4. Concentration afforded 25.4 g of an oil which was chromatographed on silica gel. Elution with 60:40 hexane:CH2 Cl2 gave 20.01 g of pure 3-chloro-5-methylbenzaldehyde.
  • 9
  • [ 62358-81-0 ]
  • [ 103426-20-6 ]
YieldReaction ConditionsOperation in experiment
42% With 2-nitropropane; sodium hydride; In ethanol; for 3.0h; [00327] To a solution of sodium metal ( 52 mg, 2.3mmol) in ethanol was added 2- nitropropane (0.23g, 2.4 mmole) followed by the addition of 3-chloro-5-methybenzylbromide (0.5g, 2.3 mmol). The reaction was allowed to stir for 3 hours and the precipitate formed was filtered off. The filtrate was concentrated under reduced pressure, redissolved in diethylether and washed with IN sodium hydroxide (twice), water, and dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified via silica gel chromatography using 10% dichloromethane and 90% petroleum ether, to give 0.15g of 3-chloro-5-methylbenzaldehyde (42%). 1H-NMR (CDCl3): 2.46 (s, 3H) 7.43(s, IH) 7.56 (s, IH) 7.68(s, IH), 9.92 (s, IH).
With 2-nitropropane; sodium ethanolate; In ethanol; for 3.0h; [0363] To a solution of sodium metal ( 52 mg, 2.3mmol) in ethanol was added 2- nitropropane (0.23g, 2.4 mmole) followed by the addition of 3-chloro-5-methybenzylbromide (0.5g, 2.3 mmol). The reaction was allowed to stir for 3 hours and the precipitate formed was filtered off. The filtrate was concentrated under reduced pressure, redissolved in diethylether and washed with IN sodium hydroxide (twice), water, and dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified via silica gel chromatography using 10% dichloromethane and 90% petroleum ether, to give 0.15g of 3-chloro-5-methylbenzaldehyde. 1H-NMR (CDCl3): 2.46 (s, 3H) 7.43(s, IH) 7.56 (s, lH) 7.68(s, IH), 9.92 (s, IH).
  • 10
  • [ 189161-09-9 ]
  • [ 103426-20-6 ]
YieldReaction ConditionsOperation in experiment
42% Preparation of 3-chloro-5-methylbenzaldehyde To a solution of sodium metal (52 mg, 2.3 mmol) in ethanol was added 2-nitropropane (0.23 g, 2.4 mmole) followed by the addition of 3-chloro-5-methybenzylbromide (0.5 g, 2.3 mmol). The reaction was allowed to stir for 3 hrs and the precipitate formed was filtered off. The filtrate was concentrated under reduced pressure, redissolved in diethylether and washed with 1N sodium hydroxide (twice), water, and dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified via silica gel chromatography using 10% dichloromethane and 90% petroleum ether, to give 0.15 g of 3-chloro-5-methylbenzaldehyde (42%). 1H-NMR (CDCl3): 2.46 (s, 3H) 7.43 (s, 1H) 7.56 (s, 1H) 7.68 (s, 1H), 9.92 (s, 1H).
  • 12
  • [ 556-97-8 ]
  • [ 103426-20-6 ]
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Julia-Kocienski Olefination • Kinetics of Alkyl Halides • Knoevenagel Condensation • Kumada Cross-Coupling Reaction • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nozaki-Hiyama-Kishi Reaction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • 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 • Reformatsky Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Stetter Reaction • 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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