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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
2,5-Dihydroxybenzaldehyde (Gentisaldehyde) is a naturally occurring antimicrobial that inhibits the growth of Mycobacterium avium subsp. paratuberculosis. 2,5-Dihydroxybenzaldehyde is active against S. aureus strains with a MIC50 of 500 mg/L.
Synonyms: Gentisaldehyde; 5-Hydroxysalicylaldehyde; NSC 72387
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Commey, Leslie ; Mechref, Yehia ; Burow, Mark ; Mendu, Venugopal ;
Abstract: The peanut seed coat acts as a physical and biochemical barrier against Aspergillus flavus infection; however, the nature of the inhibitory chemicals in the peanut seed coat in general is not known. This study identified and characterized peanut seed coat metabolites that inhibit A. flavus growth and aflatoxin contamination. Selected peanut accessions grown under well-watered and water-deficit conditions were assayed for A. flavus resistance, and seed coats were metabolically profiled using liquid chromatography mass spectrometry. Kyoto Encyclopedia of Genes and Genome phenylpropanoid pathway reference analysis resulted in the identification of several seed coat metabolic compounds, and ten selected metabolites were tested for inhibition of A.flavus growth and aflatoxin contamination. Radial growth bioassay demonstrated that 2,5-dihydroxybenzaldehyde inhibited A. flavus growth (98.7%) and reduced the aflatoxin contamination estimate from 994 to 1 μg/kg. Scanning electron micrographs showed distorted hyphae and conidiophores in cultures of 2,5-dihydroxybenzaldehyde-treated A. flavus, indicating its potential use for field application as well as seed coat metabolic engineering.
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Keywords: aflatoxin, A. flavus ; metabolomics ; seed coat ; liquid chromatography mass spectrometry (LC-MS) ; radial growth bioassay ; secondary metabolites
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CAS No. : | 1194-98-5 |
Formula : | C7H6O3 |
M.W : | 138.12 |
SMILES Code : | O=CC1=CC(O)=CC=C1O |
Synonyms : |
Gentisaldehyde; 5-Hydroxysalicylaldehyde; NSC 72387
|
MDL No. : | MFCD00003333 |
InChI Key : | CLFRCXCBWIQVRN-UHFFFAOYSA-N |
Pubchem ID : | 70949 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H317-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; triethylamine; In tetrahydrofuran; THF(35 ml); ethanol; dichloromethane; | 1) 2-[4-(6-Acryloyloxyhexyloxy)benzoyloxy]-5-(4-trans-pentylcyclohexanecarbonyloxy)benzaldehyde A solution of mesyl chloride (1.14 g) in 10 ml of dry THF is dropwise added to a cooled (-40 to -25°C) solution of 4-(6-acryloyloxyhexyloxy)benzoic acid (2.78 g) and triethylamine (6 ml) in 40 ml of dry THF and under argon. After complete addition (15 min), the reaction mixture was further stirred for 60 min at -25 °C then treated with a solution of 2,5-dihydroxybenzaldehyde (1.38 g) in 10 ml of dry THF and the reaction mixture is further stirred at -25°C for 2 h. This mixture was then treated with a suspension of triethyl-(trans-4-pentylcyclohexynecarbonyl)ammonium; chloride (prepared from trans-4-pentylcyclohexanecarboxylic acid (2.26 g), triethylamine (6 ml) and mesyl chloride (1.14 g) in THF(35 ml)) in dry THF (35 ml), followed by one-crop addition of DMAP (0.24 g). Stirring is continued for 3 h at -25°c and for 30 min at room temperature. The reaction mixture is then poured into 80 ml of saturated NaHCO3, extracted with 2 x 100 ml of ether. The combined organic extracts are washed with HCl 3N (100 ml) then with half saturated NaCl solution (2 x 100 ml), dried over MgSO4, filtered and evaporated to dryness to afford a slightly yellow pasty material. This is flash chromatographed over a short silica-gel column (CH2Cl2). The obtained white residue (2.3 g) was dissolved in CH2Cl2 (5 ml) then reprecipitated from ethanol (50 ml). This affords pure 2-[4-(6-acryloyloxyhexyloxy)benzoyloxy]-5-(4-trans-pentylcyclohexanecarbonyloxy)benzaldehyde as white crystalline material. Yield 1.3 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.4% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 25℃; for 12h;Inert atmosphere; | A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a homogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) to the solution, the mixture was stirred at 25°C for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, and extracted with 500 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1 (volume ratio)) to obtain 75 g of an intermediate A as a white solid (yield: 75.4percent). [0160] The structure of the target product was identified by 1H-NMR. [0161] 1H-NMR data for intermediate A 1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H). |
75.4% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 25℃; for 12h;Inert atmosphere; | A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde,105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g(43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare ahomogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimidehydrochloride (WSC) to the solution, the mixture was stirred at 25°C for 12 hours.[0169] After completion of the reaction, the reaction mixture was added to 1.51 of water, and extracted with 500 ml ofethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. Ethylacetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid.The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1 (volume ratio)) toobtain 75 g of an intermediate A as a white solid (yield: 75.4percent). The structure of the target product was identified by 1HNMR.[0170] 1H-NMR data for intermediate A1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H),1.58-1.42 (m, 8H). |
75.4% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 25℃; for 12h;Inert atmosphere; | Step 3: Synthesis of Intermediate C A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a homogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (hereinafter referred to as ?WSC?) to the solution, the mixture was stirred at 25° C. for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, and extracted with 500 ml of ethyl acetate. After drying the ethyl acetate layer over anhydrous sodium sulfate, sodium sulfate was separated by filtration. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1 (volume ratio (hereinafter the same))) to obtain 75 g of an intermediate C as a white solid (yield: 75.4percent). The structure of the target product was identified by 1H-NMR. 1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H) |
75.4% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 25℃; for 12h;Inert atmosphere; | Step 1: Synthesis of Intermediate E (0199) (0200) A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) to the solution, the mixture was stirred at 25° C. for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, followed by extraction with 500 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1) to obtain 75 g of an intermediate E as a white solid (yield: 75.4percent). (0201) The structure of the target product was identified by 1H-NMR. (0202) 1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H) |
75 g | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 20℃; for 12h;Inert atmosphere; | 2,5-dihydroxybenzaldehyde 20 g (144.8 mmol) in a 4-port reactor equipped with a thermometer under a nitrogen stream. 4-(6-Propyloxy-1-hexyloxy)benzoic acid (manufactured by DKSH Co., Ltd.) 105.8 g (362.0 mmol), N,N-dimethylaminopyridine (N,N-dimethyl-4) -Aminopyridine) 5.3 g (43.4 mmol) was dissolved in 200 mL of N-methylpyrrolidone (N-methyl-2-pyrrolidone). 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) 83.3 g (434.4 mmol) was added to this solution, and stirred at room temperature for 12 hours. After completion of the reaction, the reaction solution was poured into 1.5 L of water and extracted with ethyl acetate (500 mL). The ethyl acetate layer was dried over anhydrous sodium sulfate. After the sodium sulfate was filtered off, ethyl acetate was evaporated to dryness eluted from the filtrate to give a pale yellow solid. The pale yellow solid was purified by hexane column chromatography (toluene: ethyl acetate = 9:1) to afford 75 g of intermediate product Z (yield: 75.4 molpercent) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | General procedure: 2,5-Dihydroxybenzaldehyde (1.0 eq.) and cesium carbonate (1.0 eq.) were suspended in DMF and the suspension, warmed to 60 °C for 15 min. After cooling down to rt, the corresponding bromide (1.1 eq.) was added in DMF (0.5 M concentration of 2,5-dihydroxybenzaldehyde) and the reaction was stirred at rt for 2h for benzylic haloalkanes or at 60 °C overnight for aliphatic haloalkanes. The solvents were evaporated and the crude dissolved in water and ethyl acetate. The aqueous phase was extracted with ethyl acetate (3x) and the combined organic layers were dried over magnesium sulfate, filtered and the solvent evaporated. The crude product was purified by flash chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | In ethanol; at 20℃; | General procedure: Compounds 2 were prepared by the reaction between <strong>[7504-94-1]2-hydrazinylpyrimidine</strong> 1 (0.04 g, 0.36 mmol) and the appropriate aromatic or heteroaromatic aldehyde (1.0 eq., 0.36 mmol) in ethanol (3.0 mL) [27]. The reaction mixture was stirred for between 20 min and 5 h at room temperature. After rotary evaporation, the product was purified by washing with cold ethanol (2.0 mL) and cold diethyl ether (2.0 mL), leading to the pure derivatives 2a-f as solid in 27-75% yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With sodium metabisulfite; In ethanol; water; for 24h;Reflux; | General procedure: To a solution of the appropriate 3,4-diaminobenzene derivative (1ad)(2 mmol) in ethanol (15 mL) 2.85 N aqueous solution of sodium metabisulphite (1.6 mL) and the appropriate substituted arylaldehyde(2 mmol) were added. The reaction mixture was heated at reflux for 24 h. The solvent was then evaporated under reduced pressure. The residue was added with HCl 1 N (10 mL), the formed precipitate was filtered off, washed with water (3×10 mL) and purified by crystallization from the adequate solvent to give the title compounds.Following the general procedure benzimidazoles 3 [19], 4 [20], 5 [21],7 [24], 6, 32 and 33 [15] were prepared and their analytical and spectral data are in agreement with those reported in literature. |