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Chemical Structure| 18515-67-8 Chemical Structure| 18515-67-8

Structure of 3-Methyl-4-nitrobenzaldehyde
CAS No.: 18515-67-8

Chemical Structure| 18515-67-8

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Product Details of [ 18515-67-8 ]

CAS No. :18515-67-8
Formula : C8H7NO3
M.W : 165.15
SMILES Code : CC1=C(C=CC(=C1)C=O)[N+](=O)[O-]
MDL No. :MFCD08445621
InChI Key :WHJDQIWWIJARMK-UHFFFAOYSA-N
Pubchem ID :11194528

Safety of [ 18515-67-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 18515-67-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 45.62
TPSA ?

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

62.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.2
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

2.3
Log Po/w (WLOGP)?

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

1.72
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.

0.59
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

0.28
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.22

Water Solubility

Log S (ESOL):?

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

-2.55
Solubility 0.464 mg/ml ; 0.00281 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.

-3.26
Solubility 0.091 mg/ml ; 0.000551 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

-2.11
Solubility 1.29 mg/ml ; 0.00783 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.

-5.67 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

3.0 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)

1.55

Application In Synthesis of [ 18515-67-8 ]

* 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 [ 18515-67-8 ]

[ 18515-67-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 80866-75-7 ]
  • [ 18515-67-8 ]
YieldReaction ConditionsOperation in experiment
93% With pyridinium chlorochromate; In dichloromethane; at 20℃; for 3h; Step 1: 3-methyl-4-nitrobenzaldehyde: To a solution of (3-methyl-4- nitrophenyl)methanol (1.0 equiv.) in dichoromethane, pyridinium chlorochromate (1.1 equiv.) was added and the reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was filtered through celite and the filtrate was evaporated. The residue was adsorbed on silica (100-200 mesh) and purified by flash chromatography on silica gel, eluting with 5% ethyl acetate in petroleum ether (60-80), to provide the title compound in the form of creamish crystals (93%); 1H NMR (300 MHz, CDCl3) δ: 2.66 (s, 3H), 7.84-7.87 (m, 2H), 8.04-8.07 (d, J = 8.7 Hz, IH), 10.12 (s, IH); IR (KBr) 3104, 3079, 2981, 2857, 2743, 1702, 1607, 1518, 1383, 1361, 1308, 1226, 1153, 1008, 832, 735 cm"1.
With manganese(IV) oxide; In dichloromethane; at 20℃; for 48h; Intermediates 25 & 26 To a stirred solution of Intermediate 23 or 24 (60 mmol) in methylene chloride (200 mL) was added manganese oxide (52 g, 600 mmol). The reaction mixture was stirred at room temperature for 2 days and filtered through diatomaceous. The filter cake was washed with methylene chloride (500 mL) and the filtrate was concentrated under reduced pressure to afford the crude aldehyde. To a solution of the aldehyde (8.7 g, 54 mmol) at -78 0C in tetrahydrofuran (180 mL) was added MeLi (2 M in THF, 80 mmol, 40 mL) dropwise via addition funnel. The resulting solution was stirred under nitrogen, at -78 0C, for 4 hours. The reaction mixture was quenched slowly with saturated ammonium chloride solution at -78 0C and warmed to 0 C. The mixture was partitioned between ethyl acetate (500 mL) and water (300 mL). The organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure. The crude oil was purified by chromatography (silica gel, 2:1 hexanes/ethyl acetate) to afford the alcohol intermediate. To a stirred solution of EPO <DP n="65"/>the alcohol (4.0 g, 22 mmol) in methylene chloride (75 ml_) was added manganese oxide (26 g, 300 mmol). The reaction mixture was stirred at room temperature for 2 days and then filtered through diatomaceous. The filter cake was washed with methylene chloride (500 ml_) and the filtrate was concentrated under reduced pressure and the resulting solid was purified by chromatography (silica gel, 4:1 hexanes/ethyl acetate).Intermediate 25 (4.3 g, 35% for 3 steps): 1H NMR (500 MHz, CDCI3) .58.01-7.99 (m, 1 H), 7.91 (s, 1 H), 7.89-7.82 (m, 1H), 2.65-2.64 (m, 6H); HPLC >99%, tR = 8.05 min;Intermediate 26 (1.6 g, 24% for 3 steps): 1H NMR (500 MHz, CDCI3) 67.90-7.88 (m, 1 H), 7.68 (s, 1 H), 7.53-7.55 (m, 1 H), 4.01 (s, 3H), 2.65 (s, 3H).
58 g With manganese(IV) oxide; In dichloromethane; at 40℃; for 2h; A flask was charged with <strong>[80866-75-7](3-methyl-4-nitro-phenyl)-methanol</strong> (66.9 g, 0.400 mol), manganese(IV) oxide (85%, 5 μm powder, 409.1 g, 4.00 mol), and CH2Cl2 (1337 mL). The mixture was stirred at 40 C. for at least 2 h or until HPLC analysis showed that the reaction had proceeded to greater the 97% completion. The cooled batch was diluted with CH2Cl2 (1 L) and filtered through a Celite pad (34 g), and the filter cake was rinsed with more CH2Cl2 (1 L). The filtrate and washes were concentrated under in vacuo to dryness to give the title compound as a yellow solid (58 g, 87% yield).
  • 2
  • 9-(3-methyl-4-nitrophenyl)-2,3,5.6,7,9-hexahydrothieno[3.2-b]quinolin-8(4H)-one 1,1-dioxide 3-Methyl-4-nitrobenzaldehyde [ No CAS ]
  • [ 80866-75-7 ]
  • [ 7529-22-8 ]
  • [ 18515-67-8 ]
YieldReaction ConditionsOperation in experiment
silica gel; In tetrapropylammonium perruthennate; dichloromethane; EXAMPLE 219A 3-methyl-4-nitrobenzaldehyde To a solution of <strong>[80866-75-7]3-methyl-4-nitrobenzyl alcohol</strong> (3.0 g, 18 mmol), N-methylmorpholine-N-oxide (3.2 g, 27 mmol), and powdered 4A molecular sieves (8.98 g) in methylene chloride (40 mL) was added in one portion tetrapropylammonium perruthenate (0.315 g, 0.898 mmol), and the reaction stirred at room temperature. The reaction was filtered through silica gel, eluding with methylene chloride, solvent evaporated and the residue purified by flash chromatography to provide 2.2 g of the title compound. Examp~le 219B 5 9-(3-methyl-4-nitrophenyl)-2,3,5.6,7,9-hexahydrothieno[3.2-b]quinolin-8(4H)-one 1,1-dioxide 3-Methyl-4-nitrobenzaldehyde (0.99 g, 6.0 mmol) was processed according to the method of Example 11 5C to provide the title compound. mp >250; 10 1H NMR (DMSO-d6) δ 1.90 (m, 2H), 2.26 (m, 2H), 2.54 (m, 2H), 2.86 (m, 1H), 3.02 (m, 1H), 3.38 (m, 2H), 4.98 (s, 1H), 7.30 (m, 2H), 7.92 (d, 1H, J=6.0Hz)), 9.85 (s, 1H); MS (ESI+) m/z 375 (M+H)+; Anal. Calcd for C18H18N205S0.2H20: C, 57.74;H, 4.85; N, 7.48. Found: C, 56.91;H, 5.07; N, 7.07.
  • 3
  • [ 89-87-2 ]
  • [ 18515-67-8 ]
  • [ 3113-71-1 ]
  • [ 80866-75-7 ]
YieldReaction ConditionsOperation in experiment
Adding a time fresh material of the oxidation reactor 2,4-dimethyl-nitrobenzene and catalyst is dissolved in the acetic acid CeO2, naphthenic acid cobalt and having the general formula (IV) of a metal phthalocyanine structure (R1=H, R2=CH3CH2, M=Mn) mixture, the total concentration of 450 ppm, acetic acid and 2,4-dimethylnitro Benzene mass ratio of 0. 08. When the device was operated stably, the flow rate of the fresh material in the oxidation reactor was 6.0 mL / h. The average residence time of the oxidation reactor in liquid phase was 5.0 h, and the mass fraction of oxygen was 80% oxygen-enriched air was continuously fed into the oxidation reactor, maintaining the reaction temperature at 125 C and the reaction pressure at 0.6 MPa. The volume ratio of the water added into the hydrolysis reactor to the oxidation reaction liquid entering the hydrolysis reactor is 0.43: 1, and the oxygen-enriched air with the oxygen mass percentage of 80% is continuously fed, and the reaction temperature in the hydrolysis reactor is maintained at 78 C, the reaction pressure is 0. 4MPa, then the hydrolysis reactor liquid phase residence time of 5. Oh. Hydrolysis reactor out The liquid-liquid phase was continuously fed into the liquid-liquid delaminator at a temperature of 45. 8 C and a pressure of 0.3 MPa. The conversion of 2,4-dimethylnitrobenzene in the system was 97.0%, The selectivities of 3-methyl-4-nitrobenzyl alcohol, 3-methyl-4-nitrobenzaldehyde and 3-methyl-4-nitrobenzoic acid were 54.2%, 36.5% 9.3%, other by-products were not detected.
 

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