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Chemical Structure| 2103-57-3 Chemical Structure| 2103-57-3

Structure of 2,3,4-Trimethoxybenzaldehyde
CAS No.: 2103-57-3

Chemical Structure| 2103-57-3

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Product Details of [ 2103-57-3 ]

CAS No. :2103-57-3
Formula : C10H12O4
M.W : 196.20
SMILES Code : C1=C(C(=C(OC)C(=C1)OC)OC)C=O
MDL No. :MFCD00003310
InChI Key :UCTUXUGXIFRVGX-UHFFFAOYSA-N
Pubchem ID :75006

Safety of [ 2103-57-3 ]

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

Computational Chemistry of [ 2103-57-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 51.31
TPSA ?

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

44.76 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.22
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

1.3
Log Po/w (WLOGP)?

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

1.52
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.

0.55
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

2.03
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.52

Water Solubility

Log S (ESOL):?

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

-1.93
Solubility 2.31 mg/ml ; 0.0118 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.84
Solubility 2.83 mg/ml ; 0.0144 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

-2.73
Solubility 0.363 mg/ml ; 0.00185 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

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

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.

-6.57 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

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)

1.75

Application In Synthesis of [ 2103-57-3 ]

* 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 [ 2103-57-3 ]

[ 2103-57-3 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 141-78-6 ]
  • [ 2103-57-3 ]
  • [ 33130-04-0 ]
  • 2
  • [ 2103-57-3 ]
  • [ 19676-64-3 ]
YieldReaction ConditionsOperation in experiment
95% With sulfuric acid; dihydrogen peroxide; In methanol; water; at 20℃; for 24h; Synthesis of 2,3,4-trimethoxyphenolA solution of 2,3,4-trimethoxybenzaldehyde (5.0 g, 36.7 mmol) and 31% aqueous H202 (5.3 g,48 mmol) in methanol (50 mL) was stirred with sulfuric acid (0.5 mL) at room temperature for24 h, the reaction was quenched with water, and extracted with CH2C12. The organic layer waswashed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. Theresidue was purified by column chromatography on silica gel with EtOAc/hexane (15:85) toyield a pure product of 2,3,4-trimethoxyphenol (6.3 g, 95% yield). C9H,204 ‘H NMR (400 MHz,CDC13) 6.57 (1 H, d, J= 8.0 Hz), 6.50 (1 H, d, J= 8.0 Hz), 3.87 (3 H, br s), 3.83 (3 H, br s),3.74 (3 H, br s). ‘3C NMR (100 MHz, CDC13) 146.7, 143.3, 142.2, 140.5, 108.7, 107.6, 61.0,60.7, 56.4. HRMS (negative mode) calcd for C9H,,04: 183.0657, found: mlz 183.0661 [M- Hf.
94% With formic acid; dihydrogen peroxide; In dichloromethane; water; at 20℃;Reflux; 2,3,4-trimethoxybenzaldehyde (11.7 g, 59.7 mmol) was dissolved in 200 mL of DCM. H2O2 30% (15.4 mL, 2.5 equiv) and formic acid (9.2 mL, 4 equiv) were added and the solution was stirred and heated to reflux for 6 h. The reaction mixture was then allowed to cool to room temperature and stirred overnight at the same temperature. 1.5 N NaOH (200 mL) was added to the solution, and the mixture was further stirred for 15 min. The organic layer was concentrated under vacuum and the residue was gathered with the aqueous layer. 130 mL of methanol were added, and the mixture was stirred for 30 min at r.t. The methanol was evaporated, and the mixture was extracted with DCM. The crude was purified by column chromatography on silicagel (eluent: petroleum ether/ethyl acetate 7:3) to give 1b (10.3 g, 94%). 1H NMR (500MHz, CDCl3) d: 3.81 (3H, s, OCH3), 3.89 (3H, s, OCH3),3,95 (3H, s, OCH3), 5.40(1H, s, OH), 6.55 (1H, d, J = 10 Hz,CH-5), 6.61 (1H, d, J = 10 Hz, CH-6).13C NMR (500MHz, CDCl3) d:56.6 (OCH3-4), 60.9 (OCH3-3), 61.2 (OCH3-2), 107.6 (CH-5), 108.5 (CH-6), 140.1 (C-2) 142.9(C-1), 145.2 (C-3), 150.4 (C-4); EIMS m/z 184 [M]+ (100), 169 (80), 154 (20), 126 (40); anal. C,58.71; H, 6.62 %, calcd for C9H12 O4 C, 58.69;H, 6.57 %,
79% With sulfuric acid; dihydrogen peroxide; In methanol; at 0 - 20℃; for 0.5h; A solution of 2,3,4-trimethoxybenzaldehyde (20g, 100.9mmol) and sulfuric acid (2mL) in MeOH (200mL) was stirred at 0C. To the previous solution, 30% H2O2 (13.6mL, 131.2mmol) was added dropwise at 0C and then was stirred at room temperature for 30min. The solution was evaporated and extracted with EtOAc. The crude product was purified through chromatography to provide a transparent oil (14.8g, 79%; EtOAc/hexane, Rf=0.25). 1H NMR (300MHz, CDCl3): δ 3.79 (s, 3H), 3.88 (s, 3H), 3.94 (s, 3H), 5.54 (s, 1H), 6.54 (d, 1H, J=9.0Hz), 6.62 (d, 1H, J=9.0Hz).
79% With sulfuric acid; dihydrogen peroxide; In methanol; at 20℃; for 0.5h;Inert atmosphere; 4.1.7 2,3,4-Trimethoxyphenol (15) H2O2 (30%, 13.6 mL, 131.2 mmol) was added dropwise at 0 C to a solution of 2,3,4-trimethoxybenzaldehyde (20 g, 100.9 mmol), and sulfuric acid (2 mL) in MeOH (200 mL) and the resulting mixture was stirred at room temperature for 30 min. The reaction was evaporated and extracted with EtOAc. The organic layer was collected and purified by column chromatography to afford 15 (14.8 g, 79%) as a transparent oil. 1H NMR (300 MHz, CDCl3): δ 3.79 (s, 3H), 3.88 (s, 3H), 3.94 (s, 3H), 5.54 (s, 1H), 6.54 (d, J = 9.0 Hz, 1H), 6.62 (d, J = 9.0 Hz, 1H).
With sulfuric acid; dihydrogen peroxide; In methanol; at 25℃;Inert atmosphere; INTERMEDIATE 12,3,4-Trimethoxyphenol; A solution of 2,3,4-trimethoxybenzaldehyde (1,00 g, 5.10 mmol) and 30 wt/v % hydrogen peroxide (0.672 mL, 6.52 mmol) in cone. H2SO4 (0.102 mL) and MeOH (10.19 niL) was stirred overnight at 25 0C under N2. After this time the mixture was diluted with water (20 mL) and extracted with CH2Cl2 (3 x 30 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to afford the crude product. This was purified by flash chromatography (Biotage Horizon, 4OM, Si9 -30 niL/min, 100% hexanes for 360 mL, gradient to 50% EtOAc in hexanes over 2088 mL) to afford 2,3,4-trimethoxyphenol, as a colorless oil. R/ = 0.93 (50% EtOAc/hexanes). LCMS calc. = 185.1; found = 185.2 (M+H)+. 1H NMR (600 MHz, CDCl3): δ 6.62 (d, J- 9.0 Hz5 1 H); 6.55 (d, J= 8.9 Hz, 1 H); 5.49 (s, 1 H); 3.94 (s, 3 H); 3.89 (s, 3 H); 3.80 (s, 3 H).
With sulfuric acid; dihydrogen peroxide; In methanol; at 20℃; for 12h; To a solution of 2,3,4-trimethoxybenzaldehyde (1.0 g, 5.1mmol) in MeOH (7.3 mL), 31% H2O2 (0.75 mg, 6.6 mmol)and H2SO4 (0.07 mL) were added at room temperature.After stirring for 12 h at the same temperature, the volatilesolvent was removed in vacuo to leave a residue. Theresidue was treated with H2O (30 mL) and extracted twicewith CHCl3. The extract was washed with H2O, saturatedNaHCO3 aqueous solution, and brine. The organic layerwas dried over Na2SO4 and concentrated in vacuo to givecrude 2,3,4-trimethoxyphenol (1.1 g), which was used forthe next step without further purification.1H NMR (CDCl3; 400 MHz) δ 6.63 (1H, d, J = 9.0 Hz),6.56 (1H, d, J = 9.0 Hz), 5.39 (1H, s), 3.96 (3H, s), 3.90(3H, s), 3.81 (3H, s).
79 g To a solution containing 150.0 g ( 0.77 mol) of 2,3,4-trimethoxybenzaldehyde in 1000 mL of DCM was added 300.0 g (1.74 mol) of m- CPBA in five portions (30 g each) at 0C - 10C (ice-water bath). After the addition the reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was filtered to remove the solid and the filtrate was washed with aqueous NaHC03 (400 mL c 3), water (300 mL) and brine (300 mL). The organic layer was separated and dried over anhydrous Na2S04 and the mixture was filtered. The filtrate was concentrated to provide a dark yellow colored oil which was dissolved in EtOH (600 mL) and treated with a 10% aqueous KOH solution (500 mL) in one portion. The mixture was stirred at 50C for 4 h. The mixture was then cooled and acidified to pH=1 with 1 M HCI and extracted with DCM (500 mL x 3). The combined organic extracts were washed with water (500 mL) and brine (500 mL), dried over anhydrous Na2S04 and then filtered. The filtrate was concentrated and purified by silica gel chromatography (column height: 50 cm, diameter: 20 cm, 100-200 mesh silica gel, petroleum ether / EtOAc = 30/1 , 20/1 , 15/1 , 10/1) to give Int V-1 (79.0 g) as yellow oil. 1H NMR: (CDCIs, 400 MHz): d 6.63 (d, J = 8 Hz, 1 H), 6.55 (d, J = 8 Hz, 1 H), 5.38 (brs, 1 H), 3.96 (s, 3H), 3.90 (s, 3H), 3.81 (s, 3H).
79.0 g Int V-1 To a solution containing 150.0 g (0.77 mol) of 2,3,4-trimethoxybenzaldehyde in 1000 mL of DCM was added 300.0 g (1.74 mol) of m- CPBA in five portions (30 g each) at 0C - 10C (ice-water bath). After the addition the reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was filtered to remove the solid and the filtrate was washed with aqueous NaHC03 (400 mL c 3), water (300 mL) and brine (300 mL). The organic layer was separated and dried over anhydrous Na2S04 and the mixture was filtered. The filtrate was concentrated to provide a dark yellow colored oil which was dissolved in EtOH (600 mL) and treated with a 10% aqueous KOH solution (500 mL) in one portion. The mixture was stirred at 50C for 4 h. The mixture was then cooled and acidified to pH=1 with 1 M HCI and extracted with DCM (500 mL x 3). The combined organic extracts were washed with water (500 mL) and brine (500 mL), dried over anhydrous Na2S04 and then filtered. The filtrate was concentrated and purified by silica gel chromatography (column height: 50 cm, diameter: 20 cm, 100-200 mesh silica gel, petroleum ether / EtOAc = 30/1, 20/1, 15/1, 10/1) to give Int V-1 (79.0 g) as yellow oil. 1H NMR: (CDCIs, 400 MHz): d 6.63 (d, J = 8 Hz, 1H), 6.55 (d, J = 8 Hz, 1H), 5.38 (brs, 1H), 3.96 (s, 3H), 3.90 (s, 3H), 3.81 (s, 3H).

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  • 4
  • [ 13781-53-8 ]
  • [ 2103-57-3 ]
  • α-(2,3,4-trimethoxybenzylidene)thiophene-3-acetonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
72.3% EXAMPLE 21 α-(2,3,4-trimethoxybenzylidene)thiophene-3-acetonitrile was obtained in the same method as in Referential Example 1 except that 1.96 g (10.0 mmol) of 2,3,4-trimethoxybenzaldehyde (purchased from Tokyo Kasei) was used instead of 2,4,5-trimethoxybenzaldehyde and that 1.23 g (10.0 mmol) of thiophen-3-ylacetonitrile (purchased from Tokyo Kasei) was used instead of 4-bromophenylacetonitrile, and 376 mg (yield: 72.3%) of the compound as a yellow crystalline represented by the following formula was obtained in the same method as in Example 1 except that 603 mg (2.0 mmol) of the above α-(2,3,4-trimethoxybenzylidene)thiophene-3-acetonitrile was used instead of α-cyano-4-bromo-2',4',5'-trimethoxystilbene: STR144 melting point of the obtained compound was 243-245.5 C.
  • 6
  • [ 19012-02-3 ]
  • [ 109-77-3 ]
  • [ 2103-57-3 ]
  • 2-amino-6-(1-methyl-1H-indol-3-yl)-4-(2,3,4-trimethoxyphenyl)nicotinonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
26% With ammonium acetate; In toluene; for 8h;Reflux; General procedure: The substituted 1-(1H-indol-3-yl)ethanone (1 mmol), together with the respective benzaldehyde (1 mmol), malononitrile (1 mmol) and ammonium acetate (8 mmol) were dissolved in toluene (30 mL) and heated to reflux for 8 h. The solvent was removed under reduced pressure and absolute ethanol was added to the residue. The precipitate was collected by filtration and purified by silica gel column chromatography to give the desired product.
  • 7
  • [ 109-77-3 ]
  • [ 51843-24-4 ]
  • [ 2103-57-3 ]
  • 2-amino-6-(5-chloro-1H-indol-3-yl)-4-(2,3,4-trimethoxyphenyl)nicotinonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% With ammonium acetate; In toluene; for 8h;Reflux; General procedure: The substituted 1-(1H-indol-3-yl)ethanone (1 mmol), together with the respective benzaldehyde (1 mmol), malononitrile (1 mmol) and ammonium acetate (8 mmol) were dissolved in toluene (30 mL) and heated to reflux for 8 h. The solvent was removed under reduced pressure and absolute ethanol was added to the residue. The precipitate was collected by filtration and purified by silica gel column chromatography to give the desired product.
  • 8
  • [ 14208-35-6 ]
  • [ 2103-57-3 ]
  • C22H21NO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In ethanol; at 20℃; To a clear solution of 3a (1mmol) in EtOH containing 2, 4, 6-trimethoxy benzaldehyde (1mmol), 40% KOH was added and the resulting reaction mixture was stirred for complition of the reaction at r.t. (TLC control). The separated solid was filtered, washed with excess of water, neutralized with dil HCl, dried over anhydrous Na2SO4, recrystallised from ethanol to obtain product 13. The product was pure enough for further reactions.
  • 9
  • [ 7584-05-6 ]
  • [ 2103-57-3 ]
  • 6-amino-11-(2,3,4-trimethoxyphenyl)-11,12-dihydropyrido[4,3-c][1,8]phenanthroline [ No CAS ]
  • 6-(2,3,4-trimethoxyphenyl)-5,6-dihydro-11H-pyrido[3,4-i]-3-azacarbazole [ No CAS ]
  • 10
  • [ 62-53-3 ]
  • [ 446065-11-8 ]
  • [ 2103-57-3 ]
  • N-(cyclohexyl(2,3,4-trimethoxyphenyl)methyl)aniline [ No CAS ]
 

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A104374 [57415-35-7]

2-Methoxy-4-methylbenzaldehyde

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Ethers

Chemical Structure| 4055-69-0

A362192 [4055-69-0]

2,3-Dihydroxy-4-methoxybenzaldehyde

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Chemical Structure| 148-53-8

A119953 [148-53-8]

2-Hydroxy-3-methoxybenzaldehyde

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Chemical Structure| 6527-32-8

A115848 [6527-32-8]

4-(Benzyloxy)-3,5-dimethoxybenzaldehyde

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Chemical Structure| 573-11-5

A313262 [573-11-5]

2,3,4-Trimethoxybenzoic acid

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Chemical Structure| 57415-35-7

A104374 [57415-35-7]

2-Methoxy-4-methylbenzaldehyde

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