Structure of 5-Nitrosalicylaldehyde
CAS No.: 97-51-8
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CAS No. : | 97-51-8 |
Formula : | C7H5NO4 |
M.W : | 167.12 |
SMILES Code : | O=CC1=CC([N+]([O-])=O)=CC=C1O |
MDL No. : | MFCD00007337 |
InChI Key : | IHFRMUGEILMHNU-UHFFFAOYSA-N |
Pubchem ID : | 66808 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.67 |
TPSA ? Topological Polar Surface Area: Calculated from |
83.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.55 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.72 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.11 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.29 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.57 |
Solubility | 4.52 mg/ml ; 0.0271 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.04 |
Solubility | 1.51 mg/ml ; 0.00904 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.15 |
Solubility | 12.0 mg/ml ; 0.0716 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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 |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.81 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
3.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.55 |
* 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 |
---|---|---|
72% | aluminium trichloride; In hexane; water; | EXAMPLE 1 While cooling a mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether in an ice bath, 43.9 g of anhydrous aluminum chloride was added in small portions to the mixture, followed by stirring at room temperature for 10 minutes and thereafter by refluxing with heating for 22 hours. The reaction mixture was then cooled in an ice bath, and 200 ml of water was added to the mixture with full stirring, whereby white crystals were separated out. The white crystals were collected and dissolved in hot hexane, and the solution was filtered. The mother liquor was thereafter cooled, giving 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde in the form of white needlelike crystals (yield 72%). 1 H-NMR(CDCl3); deltappm 4.72(s, 2H, --CH2 Cl), 8.56(s, 2H, ArH), 10.00(s, 1H, CHO), 12.10(s, 1H, OH). |
72% | aluminium trichloride; In hexane; water; | Example 1 A mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether was cooled on an ice-bath and 43.9 g of anhydrous aluminum chloride was added in small portions. The mixture was stirred at room temperature for 10 minutes and, then, refluxed for 22 hours. This reaction mixture was cooled on an ice-bath and 200 ml of water was added with vigorous stirring, whereupon white crystals separated out. These white crystals were collected, dissolved in hot hexane and filtered and the mother liquor was cooled to give 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde as colorless needles (Yield 72%). 1H-NMR (CDCl3): deltappm 4.72 (s, 2H, -CH2Cl), 8.56 (s, 2H, ArH), 10.00 (s, 1H, CHO), 12.10 (s, 1H, OH) |
72% | aluminium trichloride; In hexane; water; | Example 1 A mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether was cooled on an ice-bath and 43.9 g of anhydrous aluminum chloride was added in small portions. The mixture was stirred at room temperature for 10 minutes and, then, refluxed for 22 hours. This reaction mixture was cooled on an ice-bath and 200 ml of water was added with vigorous stirring, whereupon white crystals separated out. These white crystals are collected, dissolved in hot hexane and filtered and the motor liquor was cooled to give 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde as colorless needles (Yield 72%). 1H-NMR (CDCl3): deltappm 4.72 (s, 2H, -CH2Cl), 8.56 (s, 2H, ArH), 10.00 (s, 1H, CHO), 12.10 (s, 1H, OH) |
With aluminum (III) chloride; | A compound having the structure shown as the final product in the scheme detailed in FIG. 4 was synthesized and characterized. Reaction step (1) (shown in isolation in FIG. 6) proceeds well and the product was characterized by 1H NMR spectroscopy (peak obtained at MW=214). This product was readily purified by recrystallization from hot n-hexane. The yield of this reaction in our hands was not established. The literature value is 89% isolated yield. L. D. Taylor and R. B. Davis, J. Org. Chem. 1963, 28, 1713. [0074] Reaction step (2) (shown in isolation in FIG. 7) also proceeded and the crude product was purified by recrystallization from ethanol/tetrahydrofuran. Small, square-shaped orange crystals were obtained over a period of two days in ca. 12% yield. Analysis of these crystals via 1H NMR spectroscopy suggests that their crystal structure may contain tetrahydrofuran (see FIG. 8). Mass spectroscopy yielded an m/z peak at 352. Further addition of tetrahydrofuran to the ethanol mixture yielded a second crop of similar crystals. However, this second crop was coated in orange-colored viscous oil, characteristic of material that had come out of solution too quickly. This material is to be further recrystallized to improve product yield. [0075] Reaction step (3) (shown in isolation in FIG. 9) was carried out under reflux (approximately 80 C.) proceeded well and yielded a solid product as expected. Previous attempts to synthesize this compound have yielded viscous oil. Purification of the product from reaction (2) appears to lead to a purer product from reaction (3) as we obtained a solid instead of an oil. This product was analyzed by 1H NMR and by ES mass spectral analysis: FW ca. 506, [M]+504 (100%). [0076] Reaction step (4) (shown in isolation in FIG. 10) was conducted overnight at pH=10-11. However, the pH dropped to a value of 9 after 24 h. Thus, the pH was again raised to a value of ca. 10 and allowed to react for a further 24 h, during which time the reaction mixture maintained its pH value of ca. 10. It appears that at least 48 hours are necessary for the reaction to go to completion as indicated by the lack of further pH change. ES mass spectral analysis indicated a prominent peak at 701 (expected mass of the ligand+Na+). [0077] Reaction step 5 (i.e., the final reaction step shown in FIG. 4) involves the insertion of the metal to the macrocycle. The sample was run through a Chelex 100 column after first neutralizing the reaction mixture to pH=7. However, upon eluting with water, only pale yellow oil was obtained. This did not display the characteristic absorbances of ca. 510 and 550 nm upon exposure to UV-light irradiation. In addition, it was observed that a band of purple-colored material was trapped at the top of the Chelex column. Various solvents were used to try to pass this band through the column, and ethanol and chloroform each were found to be effective to elute the product. This purple-colored material displayed characteristic color changes expected for the final product. UV irradiation (described in the following example) produced a product with absorbances at ca. 510 and 550 nm. Irradiation with white light eliminates these absorbance peaks. Mass spec for the product from step 5 yielded a peak at 835 and also peak at 678 (representing either free ligand or artifactual dissociation of product during electrospray). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | aluminium trichloride; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; chloromethyl methyl ether; | EXAMPLE 1 Synthesis of 3-chloromethyl-5-nitrosalicylaldehyde 5-Nitrosalicylaldehyde (2.42 g, 14.5 mmols) was suspended in 20 ml of chloromethyl methyl ether, and aluminum chloride (7.97 g, 60.0 mmols) was added while cooling in an ice bath. After stirring at room temperature for 10 minutes, the mixture was heated at 60 C. for one hour. Then, the reaction solution was poured into 100 ml of ice water while cooling in an ice bath and the resulting yellow precipitate was filtered. The resulting precipitate was recrystallized from 330 ml of hexane to give 3-chloromethyl-5-nitrosalicylaldehyde (2.49 g, 11.6 mmols) as a yellow needle-like crystal (yield 80%). 1 H-NMR(60 MHz, CDCl3); delta 4.7(s, 2 H, --CH2 Cl), 8.5(s, 2 H, ArH), 10.0(s, 1H, --CHO), 12.1(s, 1 H, --OH) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium iodide; potassium carbonate; In N-methyl-acetamide; ethyl acetate; | The <strong>[4591-55-3]dimethyl pyridine-3,5-dicarboxylate</strong> used as starting material was obtained as follows: A stirred mixture of 5-nitrosalicylaldehyde (8.36 g.), potassium carbonate (11.04 g.), potassium iodide (0.2 g.), N-(4-bromobutyl)phthalimide (15.6 g.) and dimethylformamide (120 ml.) was heated at 100 C. for 48 hours and then cooled to laboratory temperature. Saturated aqueous sodium chloride solution (1200 ml.) and ethyl acetate (300 ml.) were added and the mixture was shaken and filtered, the solid residue being retained. The layers of the filtrate were separated, the aqueous layer was extracted with ethyl acetate (200 ml.) and the combined ethyl acetate solutions were washed three times with saturated aqueous sodium chloride solution (100 ml. each time), dried over magnesium sulphate and evaporated to dryness. The combined residue and retained solid were crystallized from methanol and there was thus obtained 5-nitro-2-(4-phthalimidobutoxy)benzaldehyde, m.p. 145-148 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48%; 23% | General procedure: To a stirring solution of 2-hydroxybenzaldehyde derivative 1 (1.0 mmol), styrenesulfonyl chloride (0.20 g, 1.0 mmol), and K2CO3 (0.14 g, 1.0 mmol) in H2O (15 mL) for 2 h was added 4-hydroxycoumarin derivative 2 (1.2 mmol) or 4-hydroxyquinolinone (0.19 g, 1.2 mmol) and EDDA (20 mmol%) and the mixture was heated at reflux for 12 h. After completion of the reaction as indicated by TLC, the mixture was cooled to room temperature and the organics were extracted using CH2Cl2 (30 mL). Evaporation of the solvent under reduced pressure followed by column chromatography on silica gel using hexane-ethyl acetate (3:1), afforded products 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | In ethanol; for 1h;Reflux; | The title compound, (E)-2-(((4-bromo-2-(trifluoromethoxy)phenyl)imino)methyl)-4-nitrophenol, was prepared by reflux a mixture of a solution containing 2-hydroxy-5-nitrobenzaldehyde (0.0138 g, 0.082 mmol) in 20 ml ethanol and a solution containing <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (0.0211 g, 0.082 mmol) in 20 ml ethanol. The reaction mixture was stirred for 1 hunder reflux. The crystals of suitable for (E)-2-(((4-bromo-2-(trifluoromethoxy)phenyl)imino)methyl)-4-nitrophenol X-ray analysis were obtained from ethyl alcohol by slow evaporation (yield%35; m.p 198-200 C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation; | General procedure: A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized to give compounds 3-29. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trifluorormethanesulfonic acid; In toluene; at 60℃; for 15h;Inert atmosphere; | General procedure: To a solution of nitrosalicylaldehyde (2.0 mmol), diphenylacetylene (1.0 mmol) and trimethyl orthoformate (2.0 mmol) in toluene (5.0 mL) under nitrogen, trifluoromethanesulfonic acid (18 μL, 0.20 mmol, 20 mol%) was added. After being stirred at reflux for 15 h, methanol (5.0 mL, 0.12 mol) was added. Then the reaction mixture was quenched with H2O. The organic layer was separated and the aqueous layer was extracted with ethylacetate. The combined organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (hexane/ethylacetate = 100: 1 to 20: 1) to afford product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In ethanol; for 6h;Reflux; | 2-hydroxy-5-nitrobenzaldehyde (0.84g 5 mmol) and 5-methoxypyridin-2-amine(0.62g 5 mmol) were added to the roundbottom flask with 20 ml absolute methanol. After refluxing 2h, alarge amount of yellow is precipitated. Then the mixture was cooledto room temperature and filtered the solid. The crude product waswashed three times with methanol. Bright yellow solid: 83percent.m.p.169.6?176.2 °C. 1H NMR (400 MHz, CDCl3) delta ppm=14.69 (s,1H, OH), 9.50 (s, 1H, CH), 8.51 (s,1H, ArH), 8.51 (d, 2H, ArH), 7.39 (s,2H, ArH), 7.12 (d, 1H, ArH), 3.97 (s, 3H, CH3). 13C NMR (126 MHz,CDCl3) delta 165.36 (s), 159.89 (s), 154.05 (s), 152.22 (s), 151.53 (s),135.60 (s), 134.74 (s), 122.98 (s), 119.41 (s), 109.13 (s), 97.67 (s),55.92 (s), 44.62 (s), 12.76 (s). MS (ESI) (CH2Cl2) m/z: 272.05 (M?1).Calcd. For C13H11N3O4: C, 57.14; H, 4.06; N, 15.38; O,23.42. Found:C,57.62; H, 4.27; N, 15.69; O,23.51; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In ethanol; at 20℃; | General procedure: To a solution of benzaldehydes (1 equiv) in ethanol (10 mL) wasadded anilines (1 equiv), and the reaction mixture was stirred at roomtemperature overnight. The solid was collected by filtration and washedwith cold ethanol and hexane. |
68% | In ethanol; at 20℃; | General procedure: To a solution of benzaldehydes (1 equiv) in ethanol (10 mL) was added anilines (1 equiv), and the reaction mixture was stirred atroom temperature overnight. The solid was collected by filtration,and washed with cold ethanol and hexane. 5.4.1 (E)-2-(((3-ethynylphenyl)imino)methyl)-4-nitrophenol (1) The title compound was prepared according to general procedure (A) using 5-nitrosalicylaldehyde (200mg, 1.20mmol) and 3-aminophenylacetylene 1a (135muL, 1.20mmol, 1 equiv), yielding the pure product as a yellow solid (242mg, 76%), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid; In ethanol; at 20℃; for 8h; | General procedure: In a stirred mixture of 5-amino-2-(benzo[d]thiazol-2-yl) phenol(3a) or 4-amino-2-(benzo[d]thiazol-2-yl) phenol (3b)(1.0 mmol) and substituted salicylaldehyde (1.2m/m of 3aand 3b) in ethanol added few drops of acetic acid. The reactionmixture was stirred at room temperature for 8 h. Theprecipitate was filtered and recrystallized with hot ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | 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. |
Tags: 97-51-8 synthesis path| 97-51-8 SDS| 97-51-8 COA| 97-51-8 purity| 97-51-8 application| 97-51-8 NMR| 97-51-8 COA| 97-51-8 structure
A270221 [17028-61-4]
2-Hydroxy-3-methoxy-5-nitrobenzaldehyde
Similarity: 0.88
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P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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