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Yi Shen ;
Abstract: Developing methodologies to synthesize high-value products efficiently from simple substrates with control over the reactivity and selectivity is highly favored by the chemical industry. Employing assisted tandem catalysis, where serial reactions can be carried out in one pot, to achieve streamlined complex syntheses significantly reduces the number of steps and waste. Harnessing spatial and temporal control in catalysis enables approaches toward one-pot transformations and allows the integration of several catalytic processes. Ferrocene-based ligand_x005f_x0002_supported metal complexes represent a promising class of catalysts that can incorporate redox control over catalytic processes. We have developed a redox-controlled selective hydroamination reaction catalyzed by (thiolfan*)Zr(NEt2)2 (thiolfan*= 1, 1'-bis (2,4-di-tert-butyl-6-thiophenoxy)ferrocene). In situ switching of the catalyst’s state during the reaction enables selectivity toward different substrates (Chapter 2). Incorporating the greenhouse gas CO2 into N-carboxyanhydrides (NCAs) followed by subsequent NCA utilization illustrates the possibility of integrating two synthetic steps in one vessel to afford a valuable material with possible CO2 recycling. To demonstrate the immense potential of integrating multi-step transformations in one pot, we developed a set of sustainable conditions for NCA synthesis (Chapter 3). Moreover, several metal catalysts supported by ferrocene-based ligands were found to catalyze NCA polymerization in the presence of a co_x005f_x0002_catalyst. To establish an integrated system composed of two incompatible processes, we aimed to compartmentalize the active reagents for each step. The structure of the ferrocene-based pro-ligand was modified for surface anchoring. Our efforts toward immobilizing ferrocene-supported metal catalysts onto conductive surfaces pave the way of achieving spatiotemporal control over the processes of NCA synthesis and polymerization (Chapter 4). In addition to the redox-switchable characteristic, ferrocene-based compounds provide a unique platform to support lanthanides and engender distinctive optical properties to them. We synthesized and characterized a series of ytterbium complexes displaying an ultra-narrow absorption in the ultraviolet-visible (UV-Vis) region. The extraordinarily narrow linewidth observed for (thiolfan)YbCl(THF) (thiolfan = 1,1′-bis(2,4-di-tert-butyl-6-thiomethylenephenoxy)ferrocene) allows us to investigate its applications toward magnetic field and liquid cell quantum sensing (Chapter 5)
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CAS No. : | 118-48-9 |
Formula : | C8H5NO3 |
M.W : | 163.13 |
SMILES Code : | O=C(NC1=CC=CC=C12)OC2=O |
MDL No. : | MFCD00006700 |
InChI Key : | TXJUTRJFNRYTHH-UHFFFAOYSA-N |
Pubchem ID : | 8359 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P261-P264-P272-P280-P302+P352-P305+P351+P338-P321-P333+P313-P337+P313-P363-P501 |
* 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 |
---|---|---|
In toluene; at 100℃; for 12h; | General procedure: 7.1.13. Solution-phase synthesis of library compounds 21Isatoic anhydride (20) (0.1 mmol) was partitioned into reaction vials and treated with aniline (0.10 mmol) in toluene (1.0 mL) at 100 C for 12 h. The mixture in each vessel was allowed to coolto ambient temperature, and the solvent was removed under reduced pressure. The residue in each vessel was dissolved in pyridine(1.0 mL) and treated with compound 37 (0.10 mol) at ambient temperature for 12 h. The mixture was then treated with polymer-bound tris(2-aminoethyl)amine for 12 h and filtered off. The filtrate was collected in vials and the solutions were evaporatedin vacuo to afford anthranilamide derivatives 21, which were analyzed by HPLC and MS. 21a; FAB-MS m/z 443 [M+H]+, 21b; FABMS m/z 443 [M+H]+, 21c; FAB-MS m/z 443 [M+H]+, 21d; FAB-MS m/z 463 [M+H]+, 21e; FAB-MS m/z 463 [M+H]+, 21g; FAB-MS m/z459 [M+H]+, 21h; FAB-MS m/z 489 [M+H]+, 21i; FAB-MS m/z 493[M+H]+, 21j; FAB-MS m/z 513 [M+H]+, 21k; FAB-MS m/z 521[M+H]+, 21l; FAB-MS m/z 472 [M+H]+, 21m; FAB-MS m/z 457 [M+H]+, 21n; FAB-MS m/z 471 [M+H]+, 21o; FAB-MS m/z 430[M+H]+, 21p; FAB-MS m/z 444 [M+H]+, 21q; FAB-MS m/z 444[M+H]+, 21r; FAB-MS m/z 444 [M+H]+, 21s; FAB-MS m/z 460 [M+H]+, 21t; FAB-MS m/z 449 [M]+, 21u; FAB-MS m/z 433[M+H]+, 21v; FAB-MS m/z 469 [M+H]+, 21w; FAB-MS m/z 480[M+H]+. Compound 21f was obtained from 2-amino-5-chloro-3-hydroxy-40-methoxybenzanilide using the methods described forthe synthesis of compound 19 as a colorless solid (423 mg, 56%): | |
With ethyl acetate; at 70℃; for 24h; | General procedure: A flame-dried 25 mL reaction tube was placed with a stirring bar. Then, Nmethylisatoicanhydride (2 mmol), amine compounds (1.0 equiv) and EtOAc (4.0 mL)were added. The resulting mixture was stirred at 70 for 24 hours. Then, the reactionmixture was concentrated and purified by column chromatography (silica gel) to givethe target product A. A flame-dried 100 mL round-bottom flask was placed with a stirring bar. Then, A (1.5 mol), R2B(OH)2 (1.5 equiv), CuCl (20 mol%), Et3N (50 mol%) and MeOH (30 mL)were added, The resulting mixture was stirred at room temperature for 12 hours. Then,the reaction mixture was filtered, concentrated, and purified by columnchromatography (silica gel) to give the target product B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 100℃; for 12h; | General procedure: 7.1.13. Solution-phase synthesis of library compounds 21Isatoic anhydride (20) (0.1 mmol) was partitioned into reaction vials and treated with aniline (0.10 mmol) in toluene (1.0 mL) at 100 C for 12 h. The mixture in each vessel was allowed to coolto ambient temperature, and the solvent was removed under reduced pressure. The residue in each vessel was dissolved in pyridine(1.0 mL) and treated with compound 37 (0.10 mol) at ambient temperature for 12 h. The mixture was then treated with polymer-bound tris(2-aminoethyl)amine for 12 h and filtered off. The filtrate was collected in vials and the solutions were evaporatedin vacuo to afford anthranilamide derivatives 21, which were analyzed by HPLC and MS. 21a; FAB-MS m/z 443 [M+H]+, 21b; FABMS m/z 443 [M+H]+, 21c; FAB-MS m/z 443 [M+H]+, 21d; FAB-MS m/z 463 [M+H]+, 21e; FAB-MS m/z 463 [M+H]+, 21g; FAB-MS m/z459 [M+H]+, 21h; FAB-MS m/z 489 [M+H]+, 21i; FAB-MS m/z 493[M+H]+, 21j; FAB-MS m/z 513 [M+H]+, 21k; FAB-MS m/z 521[M+H]+, 21l; FAB-MS m/z 472 [M+H]+, 21m; FAB-MS m/z 457 [M+H]+, 21n; FAB-MS m/z 471 [M+H]+, 21o; FAB-MS m/z 430[M+H]+, 21p; FAB-MS m/z 444 [M+H]+, 21q; FAB-MS m/z 444[M+H]+, 21r; FAB-MS m/z 444 [M+H]+, 21s; FAB-MS m/z 460 [M+H]+, 21t; FAB-MS m/z 449 [M]+, 21u; FAB-MS m/z 433[M+H]+, 21v; FAB-MS m/z 469 [M+H]+, 21w; FAB-MS m/z 480[M+H]+. Compound 21f was obtained from 2-amino-5-chloro-3-hydroxy-40-methoxybenzanilide using the methods described forthe synthesis of compound 19 as a colorless solid (423 mg, 56%): |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; at 150℃; for 6h; | Example 9 [N- (1-ACETYL-3,] 3-dimethyl-2, [3-DIHYDRO-LH-INDOL-6-YL)-2-] [ [(QUINOLIN-4-YLMETHYL)-AMINO]-BENZAMIDE] Step A: Preparation of [N- (1-ACETYL-3,] 3-dimethyl-2,3- [DIHYDRO-LH-INDOL-6-YL)-2-AMINO-BENZAMIDE] A mixture of 1- (6-amino-3, 3-dimethyl-2,3-dihydro- indol-1-yl)-ethanone (1.02 g, 5 mmol) and isatoic anhydride (0. 85 g, 5.2 mmol) in DMSO (5 mL) was heated to 150 [C] for 6 h. After cooling to RT, the mixture was suspended in a [NAHC03] solution (40 mL) and extracted with [CH2CL2] [(20] mL x 3). The organic solution was combined and concentrated in vacuo. The residue was purified via flash chromatography on silica gel (EtOAc: hexanes 9: 2) to give the desired compound as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Example 4Preparation of 2-Amino-N-(2-methyl-2H-indazol-6-yl)-benzamide; A solution of 34.9 g isatinic anhydride, 30 g <strong>[50593-30-1]6-amino-2-methyl-2H-indazole</strong> and 12.2 ml acetic acid in 94 ml 2-butanol were stirred for 6 hours at 100 C. After evaporation of 70 ml 2-butanol, 45 ml methanol were added and after further 45 min. at 65 C. the reaction was cooled to room temperature. The suspension was filtered and the solution was distilled to remove the methanol. At 45 C. about 45 ml ethyl acetate and 30 ml triethylamine were added. To this solution, 250 ml MTBE were added slowly at 45 C. to precipitate the title compound as a pale material that was filtered off. After drying, 47 g (86%) of 2-Amino-N-(2-methyl-2H-indazol-6-yl)-benzamide were isolated.1H-NMR (300 MHz, CDCl3): delta=4.18 (s, 3H); 6.29 (s, 2H); 6.56 (t, 1H); 6.72 (d, 1H); 7.16 (dt, 1H); 7.25 (dd, 1H); 7.55-7.65 (m, 2H); 8.05 (s, 1H); 8.20 (s, 1H); 9.95 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | DIAD (0.9 mL, 1 eq) in THF (2 mL) was added dropwise to a stirred solution containing (l-isopentyl-lH-benzo[d]imidazol-2-yl)methanol (1.0 g), RhoRho1¾ (1.2 g, 1 eq) and isatoic anhydride (748 mg, leq) in THF (30 mL) and stirred overnight. The reaction was concentrated to a light brown residue that was taken up in DMF (20 mL) and treated with <strong>[42303-42-4]ethyl <strong>[42303-42-4]1-aminocyclopropanecarboxylate hydrochloride</strong></strong> (1.05 g, 1.5 eq) and heated to 75C for 48 h. Aqueous workup between Et20 and water gave a brown foam (11.2 g) . This crude ester was dissolved in 2 M NaOH / EtOH (4: 1, 10 mL) and warmed to 70C for 5 h. The cooled reaction was concentrated, taken up in 2M NaOH and washed with Et20. The aqueous phase was acidified to pH 4 with 2M HCl and extracted into EtOAc (2 x 25 mL). This gave an impure brown foam which was purified on silica gel with isohexane / EtOAc (3:1 to 1 :1) as eluant. This gave the desired acid as the more polar component as a cream solid (279mg, 15%). ? NMR (400 MHz, DMSO): delta 8.85 (1H, s), 8.8 (1H, t), 7.58 (1H, d), 7.48 (1H, d),7.349 (1H, dd), 7.18 (3H, m), 6.93 (1H, d), 6.55 (1H, t), 4.68 (2H, d), 4.29 (2H, m), 1.67 (1H, sept), 1.578 (2H, m), 1.085 (2H, m), 0.94 (8H, d). LC/MS 421.5 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With water; at 20.0℃; for 3.0h;Green chemistry; | General procedure: A mixture of isatoic anhydride (1 mmol), amine (1 mmol), and aromatic aldehyde (1 mmol) in H2O (5 mL) was stirred at room temperature for 2-3 h. After the completion of reaction (checked by TLC), the precipitate was filtered off and recrystallized from ethanol to give the pure compound 6 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 100℃; for 12h; | General procedure: 7.1.13. Solution-phase synthesis of library compounds 21Isatoic anhydride (20) (0.1 mmol) was partitioned into reaction vials and treated with aniline (0.10 mmol) in toluene (1.0 mL) at 100 °C for 12 h. The mixture in each vessel was allowed to coolto ambient temperature, and the solvent was removed under reduced pressure. The residue in each vessel was dissolved in pyridine(1.0 mL) and treated with compound 37 (0.10 mol) at ambient temperature for 12 h. The mixture was then treated with polymer-bound tris(2-aminoethyl)amine for 12 h and filtered off. The filtrate was collected in vials and the solutions were evaporatedin vacuo to afford anthranilamide derivatives 21, which were analyzed by HPLC and MS. 21a; FAB-MS m/z 443 [M+H]+, 21b; FABMS m/z 443 [M+H]+, 21c; FAB-MS m/z 443 [M+H]+, 21d; FAB-MS m/z 463 [M+H]+, 21e; FAB-MS m/z 463 [M+H]+, 21g; FAB-MS m/z459 [M+H]+, 21h; FAB-MS m/z 489 [M+H]+, 21i; FAB-MS m/z 493[M+H]+, 21j; FAB-MS m/z 513 [M+H]+, 21k; FAB-MS m/z 521[M+H]+, 21l; FAB-MS m/z 472 [M+H]+, 21m; FAB-MS m/z 457 [M+H]+, 21n; FAB-MS m/z 471 [M+H]+, 21o; FAB-MS m/z 430[M+H]+, 21p; FAB-MS m/z 444 [M+H]+, 21q; FAB-MS m/z 444[M+H]+, 21r; FAB-MS m/z 444 [M+H]+, 21s; FAB-MS m/z 460 [M+H]+, 21t; FAB-MS m/z 449 [M]+, 21u; FAB-MS m/z 433[M+H]+, 21v; FAB-MS m/z 469 [M+H]+, 21w; FAB-MS m/z 480[M+H]+. Compound 21f was obtained from 2-amino-5-chloro-3-hydroxy-40-methoxybenzanilide using the methods described forthe synthesis of compound 19 as a colorless solid (423 mg, 56percent): |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With pyridine; at 120℃; for 18h; | Isatoic anhydride (compound l) (1 g, 6.13 mmol) and <strong>[2886-33-1]L-aspartic acid dibenzyl ester p-toluenesulfonate salt</strong> (compound 6) (1 g, 6.13 mmol) are dissolved in pyridine to form a chemical solution, and the chemical solution is heated to 120 C. and reacted for 18 hours. Afier 18 hours, the reaction solution is cooled to room temperature, and drops of 6N HC1 are added gradually to acidify the reaction solution to a pH value of 1. The acidified reaction solution is extracted by ethyl acetate, and the combined organic layer is washed by saturated salt water to remove the salts, and then anhydrous magnesium sulfate is used for drying and filtering. The filtered solution is concentrated to form a crude product, and the crude product is re-crystallized by ethyl acetate and water to obtain the final white solid product which is the compound 7A(0.36g,18%) Analysis Data of Compound 7A ?H-NMR (300 MHz, DMSO-d5): oe 2.78 (dd, 1H),2.90 (dd, 1H), 4.07 (ddd, 1H), 5.07 (s, 2H), 7.10 (d, 1H), 7.27 (dd, 1H), 7.33 (m, 5H), 7.75 (dd, 1H), 8.62 (dd, 1H), 10.4 (s, NH); ?3C-NMR(75 MHz, DMSO-d5): oe 171.3, 170.4, 168.1, 137.0, 136.4, 132.8, 130.9, 128.8, 128.4, 128.1, 126.7, 124.7,121.5, 66.0, 49.1, 33.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With copper(l) iodide; ammonium acetate; In neat (no solvent); at 120℃; for 4h; | General procedure: A mixture of isatoic anhydride (1.0 mmol), benzonitrile(1.0 mmol), NH4OAc (4.0 mmol), and CuI (0.1 mmol)was heated for 4 h at 120 C. After completion of thereaction as indicated by TLC monitoring, the reactionmixture was cooled to room temperature, and the residuewas purified by column chromatography using n-hexane-EtOAc (4:1) as eluent. The solvent was removed, and thepure product 3a was obtained as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With toluene-4-sulfonic acid; In ethanol; water; at 20℃; for 0.916667h;Sonication; | General procedure: An equimolar amount of Isatoic anhydride (1mmol) and 2-Furoic hydrazide (1mmol) was taken in 50mL round bottom flask containing 10mL of ethanol: water (5:5 v/v) mixed solvent and P-TSA (20mol%). The resultant reaction mixture was sonicated till the completion of reaction. Then the respective substituted salicylaldehydes (1mmol) were added in it. The reaction mixture was further sonicated, and the progress of reaction was monitored on thin layer chromatography (TLC). After completion of reaction the product was isolated by simple filtration method and washed with ethanol. The formation of product was confirmed by spectral techniques such as IR, NMR and LCMS Analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | General procedure: β-Cyclodextrin (30 mol %), isatoic anhydride (1.0 mol eq.) and substituted isatin (1.0 mol eq.), were mixed in 8 mL water followed by stirring for 0.5 h at room temperature. Then primary amine (1.0 mol eq.) was added and reaction mixture was stirred vigorously upto disappearance of reactants on TLC (monitored by silica TLC). After completion reaction mixture was extracted by ethyl acetate and evaporated under reduced pressure. Solid residue was further crystallized by methanol and filtrate was kept for catalyst recovery. |
Tags: Isatoic anhydride | Ketones | Carbamates | Oxazines | Ser/Thr Protease | Protease | Heterocyclic Building Blocks | Organic Building Blocks | 118-48-9
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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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