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CAS No. : | 3383-21-9 | MDL No. : | MFCD00001647 |
Formula : | C14H20O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | NOUZOVBGCDDMSX-UHFFFAOYSA-N |
M.W : | 220.31 | Pubchem ID : | 76915 |
Synonyms : |
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.57 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 66.23 |
TPSA : | 34.14 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.33 cm/s |
Log Po/w (iLOGP) : | 2.48 |
Log Po/w (XLOGP3) : | 3.26 |
Log Po/w (WLOGP) : | 3.08 |
Log Po/w (MLOGP) : | 2.19 |
Log Po/w (SILICOS-IT) : | 3.35 |
Consensus Log Po/w : | 2.87 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.13 |
Solubility : | 0.164 mg/ml ; 0.000745 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.65 |
Solubility : | 0.0492 mg/ml ; 0.000223 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.25 |
Solubility : | 0.122 mg/ml ; 0.000556 mol/l |
Class : | Soluble |
PAINS : | 2.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 3.86 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
100% | With periodate form of Amberlyst A26 In chloroform at 20℃; for 0.75h; further reagent; | |
100% | With potassium permanganate In dichloromethane for 3h; Ambient temperature; | |
100% | With 3,3-dimethyldioxirane In propan-2-one |
100% | With tert.-butylhydroperoxide; tris(triphenylphosphine)ruthenium(II) chloride In benzene at 0℃; for 3h; | |
100% | With oxygen; triethylamine In propan-2-one at 20℃; for 0.5h; | |
100% | With 3Cu(2+)*4C27H21N3O6*11C2H3N*6BF4(1-)*16H2O In chloroform at 40℃; for 4h; | |
100% | With copper(II) tetrafluoroborate hexahydrate; C26H50N12(2+)*2F6P(1-); oxygen; copper chloride (II) In acetonitrile at 60℃; for 2h; Schlenk technique; | |
99% | With oxygen In tetrahydrofuran at 25℃; for 5h; | |
99% | With oxygen In chloroform; lithium hydroxide monohydrate at 20℃; for 8h; | |
99% | With oxygen In toluene at 25℃; for 24h; | |
99% | With dihydrogen peroxide In tetrahydrofuran; lithium hydroxide monohydrate at 0 - 20℃; for 48h; | 7 General procedure for 4 catalyzed H2O2 oxidation of dihydroxy arenes General procedure: The polymer-supported Ru(II)/dm-Pheox complex 4 (160.0 mg, 2.2 mol %) was suspended in THF (3.0 mL). Dihydroxy arene of 1.0 mmol was added with constant stirring at 0 C followed by the addition of H2O2 (30% aq, 0.15 mL, 1.3 mmol). The reaction mixture was then stirred at room temperature. After the starting materialhad completely oxidized, diethyl ether (3.0 mL) was added, followed by centrifugation of the mixture. The quinone product was collected by decantation and the polymeric-catalyst was quantitatively recovered by washing the residue with diethyl ether (33.0 mL). The polymeric-catalyst was dried under vacuum beforethe next cycle. The collected product was dried over anhydrous Na2SO4 and condensed under vacuum to afford the corresponding quinone in a pure form. |
99% | With Au/C; potassium carbonate In chloroform; lithium hydroxide monohydrate at 20℃; for 18h; | |
99% | With sodium (meta)periodate; tetrabutylammonium bromide In dichloromethane; lithium hydroxide monohydrate at 20℃; for 1h; | |
99% | With oxygen; C48H13Cu2F20N5O2 at 50℃; for 12h; | |
98% | With cerium(IV); mesoporous silica In dichloromethane for 0.0833333h; Ambient temperature; | |
98% | With glacial acetic acid; NaNO2 at 20 - 25℃; for 2.5h; | |
98% | With oxygen In carbon dioxide at 60℃; for 15h; | |
98% | With sodium hypochlorite pentahydrate In lithium hydroxide monohydrate; ethyl acetate at 0℃; for 0.666667h; chemoselective reaction; | Representative Procedure for Method B (Table 1, Entry 11 = Table S1, Entry 5) General procedure: For convenience, an aqueous solution of NaOCl (10 wt%) was prepared from NaOCl·5H2O (Wako) and deionized-H2O at 0 °C immediately and stored at 0 °C. To a stirring mixture of 1b (29.2 mg, 0.100 mmol) in EtOAc (5.00 mL) and deionized-water (0.180 mL) was added 10 wt% aqueous NaOCl (Wako, 70.0 μL, 0.110 mmol, 1.1 equiv) prepared above at 0 °C. The reaction was monitored by TLC analysis. After 5 min, the resulting mixture was quenched by saturated aqueous Na2S2O3 (ca. 5 mL) and saturated aqueous NaHCO3 (ca. 5 mL) at 0 °C. The aqueous layer was separated and extracted with EtOAc (twice). The combined organic layers were washed with brine. The combined organic layers were dried over anhydrous MgSO4, and then the solvents were removed in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexane-EtOAc = 10:1 to 2:1) to give desired product 2b (27.9 mg, 0.961 mmol, 96% yield). |
98% | With manganese oxide octahedral molecular sieve-supported copper hydroxide; air In ethanol at 20℃; for 1h; Green chemistry; | |
97% | With laccase; 2,3-dimethyl-buta-1,3-diene In acetate buffer at 3 - 20℃; for 24h; | |
97% | With oxygen; mesoporous silica In dichloromethane at 25℃; for 4.5h; | 3.3. General Procedure for P1/Silica-gel Combined Catalyst Catalyzed Aerobic Oxidation of Various Dihydroxy Arenes General procedure: In a two-neck 100 ml round bottomed flask connected tomolecular oxygen balloon (1.0 atm) and containing dihydroxyarene (0.1 mmol), P1 (100 mg, 0.1 mmol/g loading)and 250 mg silica-gel, a 3.0 mL of CH2Cl2 was injected and the reaction mixture was stirred at room temperature and followed by TLC until the starting material had completely converted to quinone. The quinone product was extracted with CH2Cl2 or ether and was obtained under reduced pressure.The further purification of most of the quinone product was not necessary. The P1/silica-gel combined catalyst was washed several times with ether or CH2Cl2 until it became completely clean and dried under vacuum to be ready for the next cycle. |
96% | With polystyrene-bound selenoxide In glacial acetic acid for 4.5h; Ambient temperature; | |
96% | With glacial acetic acid; NaNO2 In lithium hydroxide monohydrate at 20℃; for 1h; | |
96% | With lithium hydroxide monohydrate; oxygen In chloroform at 20℃; for 28h; | |
95% | With dihydrogen peroxide In tetrahydrofuran at 20℃; for 1.1h; | |
95% | With oxygen; triethylamine In 1,2-dichloro-ethane at 65℃; | |
95% | With sodium (meta)periodate; ammonium acetate In ethyl acetate at 50℃; for 3h; Inert atmosphere; | |
94% | With iodic acid In lithium hydroxide monohydrate; propan-2-one at 20℃; for 2h; | |
94% | With C48H90N12Si2(2+)*2F6P(1-) In [D3]acetonitrile for 95.55h; Inert atmosphere; Schlenk technique; Sealed tube; | |
91% | With [bis(acetoxy)iodo]benzene In methanol Ambient temperature; | |
91% | With sodium chlorine monoxide In dichloromethane at -10 - -5℃; for 0.166667h; | |
91% | With [bis(acetoxy)iodo]benzene In methanol at 20℃; for 0.666667h; | |
91% | Stage #1: 3,5-Di-tert-butylcatechol With 1,3,5-Tri-tert-butylbenzene In deuterated methanol at 20℃; for 24h; Stage #2: With C36H78Cu2N6O2(2+)*2CF3O3S(1-); oxygen In deuterated methanol | |
89.7% | With [CuII(N-(2-hydroxypropyl)-3-methoxysalicylaldimine(-1H))2] In methanol | 3.4 Catecholase activity of 1 and 2: spectrophotometric study In order to study the catecholase activity of complexes 1 and 2, 3,5-DTBC, with two bulky t-butyl substituents on the ring and a low quinone-catechol reduction potential, was chosen as the substrate. This makes it easily oxidized to the corresponding o-quinone, 3,5-DTBQ, which is highly stable and shows a maximum absorption at 401 nm in methanol [9c]. Solutions of 1 and 2 were treated with 100 equivalents of 3,5-DTBC under aerobic conditions. The repetitive UV-Vis spectral scan was recorded in pure methanol (Figs. 4 and 5). Spectral bands at 250, 284, 362 and 575 nm appeared in the electronic spectrum of complex 1, whereas 3,5-DTBC showed a single band at 282 nm. As the reaction proceeded, there was a gradual decrease in intensity of the band at 282nm due to the catechol and a new band was formed at ~388nm, which indicated the formation of the respective quinone derivative, 3,5-DTBQ, which was purified by column chromatography. Initially, complex 2 showed bands at ~282 and ~408nm in methanol. After addition of 3,5-DTBC, the time dependent spectral scan showed a very smooth growth of the quinone band at ~401nm, with a concomitant decrease in the characteristic ~282nm band for 3,5-DTBC. In each case, the product 3,5-DTBQ was purified by column chromatography, isolated in high yield (89.70% for 1 and 75.45% for 2) by slow evaporation of the eluant and identified by 1H NMR spectroscopy (Figs. S1 and S2; Supplementary file). 1H NMR (CDCl3, 400 MHz) δH: 1.16 (s, 9H), 1.20 (s, 9H), 6.15 (d, J=2.4 Hz, 1H), 6.86 (d, J=2.4 Hz, 1H). In order to find out the comparative reaction rate between 3,5-DTBC and each of 1 and 2, the reaction kinetics between 1/2 and 3,5-DTBC was studied by observing the time dependent change in absorbance at a wavelength of 401 nm, which is characteristic of 3,5-DTBQ in methanol. The color of the solution gradually turned deep brown, indicative of the gradual conversion of 3,5-DTBC to 3,5-DTBQ. The difference in absorbance ΔA at 401 nm was plotted against time to obtain the rate for that particular catalyst to substrate concentration ratio (Figs. 6 and 7). A first-order catalytic reaction was observed, with the rates 4.4×10-5min-1 for 1 and 8.15×10-4min-1 for 2. |
89.7% | With Ni(CH2(CH2NCHC10H6O)2) In acetonitrile at 20℃; | |
88% | With tetrabutylammonium (meta)periodate In methanol; dichloromethane Ambient temperature; other oxidants, other solvents, with catalyst, various reaction times; | |
88% | With tetrabutylammonium (meta)periodate In methanol; dichloromethane Ambient temperature; | |
88% | With benzeneseleninic anhydride In tetrahydrofuran for 0.25h; Ambient temperature; | |
88% | With dihydrogen peroxide In dichloromethane; lithium hydroxide monohydrate; acetonitrile for 0.0833333h; | |
85% | With glacial acetic acid; NaNO2 In lithium hydroxide monohydrate at 20℃; for 1h; | |
83.8% | With [Cu(2,2'-dipyridylamine)2NCS]2[Cu(2,2'-dipyridylamine)2(NCS)2](ClO4)2 In acetonitrile at 25℃; | 2.5 Catalytic oxidation of 3,5-DTBC In order to study the catecholase activity of thecomplex, a 10-4M solution of 1 in acetonitrile wastreated with 100 equiv. of 3,5-di-tert-butylcatechol (3,5-DTBC) under aerobic conditions at room temperature.Absorbance vs. wavelength (wavelength scans) of thesesolutions were recorded at a regular time interval of5 min in the wavelength range 300-900 nm.The kinetics of oxidation of 3,5-DTBC were determinedby the method of initial rates and monitored thegrowth of the quinone band at 393 nm as a functionof time.20 23 Kinetic experiment was performed with 1(at a constant concentration of 1 × 10-4 M) and 3,5-DTBC (varying the concentration from 1 × 10-3 M to1 × 10-2 M) in acetonitrile using UV-Vis spectrophotometer.2mL of 3,5-DTBC solution at appropriate concentration,obtained by accurate dilution from the stocksolution, was taken in the UV-Vis quartz cell (1 cm)and kept for a while inside the cell holder which wasattached with a thermostat to keep the temperature at25C. Then, 0.04mL of stock solution of the complexwas added to it to achieve the ultimate concentration ofthe complex as 1×10-4 M. The formation of 3,5-DTBQwas monitored with time at a wavelength of 393 nm.Each experiment was performed in triplicate. |
82% | With NaNO2 In lithium hydroxide monohydrate; glacial acetic acid | |
82% | With piperidine; C43H36FeN3O3; oxygen In chloroform-d1 at 20℃; for 2h; | |
81% | With glacial acetic acid; NaNO2 at 20℃; for 1h; | |
80% | With oxygen In methanol at 23℃; for 120h; aqueous borate buffer; | |
75% | With sodium (meta)periodate In dichloromethane at 20℃; for 3h; | |
75.8% | With C28H26N4NiO2S2; oxygen In methanol for 4h; | 3.4. Catecholase activity of 1 and 2: spectrophotometric study For the study of the catecholase activity of complexes 1 and 2, 3,5-DTBC, with two bulky t-butyl substituents on the ring and alow quinone-catechol reduction potential, has been chosen as the substrate. This makes it easily oxidizable to the corresponding o-quinone, 3,5-DTBQ, which is highly stable and shows a maximum absorption at 401 nm in methanol. Solutions of 1 and 2 were treated with 100 equivalents of 3,5-DTBC under aerobic conditions. Repetitive UV-Vis spectral scans for both complexes were recorded in pure MeOH (Figs. 3 and 4). Spectral bands at 250, 390 and 600,and 218, 244, 372 and 610 nm appeared in the electronic spectra of complexes 1 and 2, respectively whereas 3,5-DTBC shows a singleband at 282 nm. After addition of 3,5-DTBC, the time dependent spectral scans show a very smooth growth of the quinone band at 401 nm, as reported by Krebs et al. [25], concomitant with a decrease in the characteristic 282 nm band for 3,5-DTBC, which indicates the formation of the respective quinone derivative, 3,5-DTBQ, that was subsequently purified by column chromatography. The product was isolated in high yield (71.1% and 75.8% for 1 and 2, respectively) by slow evaporation of the eluant and was identifiedby 1H NMR spectroscopy (Figs. S3 and S4; Supporting information). 1H NMR (CDCl3, 400 MHz) for 1, δH (ppm): 1.22 (s, 9H), 1.26 (s, 9H), 6.21 (d, J = 2.4 Hz, 1H), 6.93 (d, J = 2.0 Hz, 1H). For 2, δH (ppm): 1.16 (s, 9H), 1.20 (s, 9H), 6.15 (d, J = 2.4 Hz, 1H), 6.86 (d, J = 2.4 Hz, 1H). |
73.7% | With [Cu(1,10-phenanthroline)(OH2)2(NO3)](NO3); oxygen In methanol at 25℃; for 1h; | 2.5. Catalytic oxidation of 3,5-DTBC In order to examine the catecholase activity of the complex, a10-4 M solution of 1 in methanol solvent was treated with100 equiv. of 3,5-di-tert-butylcatechol (3,5-DTBC) under aerobicconditions at room temperature. Absorbance versus wavelength(wavelength scans) of these solutions were recorded at a regulartime interval of 5 min in the wavelength range 300-500 nm.The kinetics of oxidation of 3,5-DTBC were determined by themethod of initial rates and involved monitoring the growth ofthe quinone band at 400 nm as a function of time [33]. Kineticexperiment was performed with 1 (at a constant concentration of1 x 10-4 M) and 3,5-DTBC (varying the concentration from1 x 10-3 M to 1 x 10-2 M) in methanol adopting UV-Vis spectrophotometer.The experimental procedure involved the preparationof stock solutions of the mononuclear Cu(II) complex and thesubstrate 3,5-DTBC at higher concentrations in methanol medium.2 mL of 3,5-DTBC at appropriate concentration, obtained by accuratedilution from the stock solution, was taken into the UV-Visquartz cell and kept for a while inside the cell holder which wasattached with a thermostat to keep the temperature at 25 °C. Then,0.04 mL of stock solution of the complex was added to it to achievethe ultimate concentration of the complex as 1 x 10-4 M. The formationof 3,5-DTBQ was monitored with time at a wavelength of400 nm. The initial rate method was applied to determine the rateconstant value for each concentration of the substrate and eachexperiment was repeated thrice. |
72% | With C28H28N2NiO4 In acetonitrile at 25℃; | |
70% | With [Co(SCN)2(N,N'-(bis(pyridine-2-yl)benzilidene)-1,2-ethanediamine)]; oxygen In acetonitrile for 6h; | 3.3. Catecholase activity of 1: spectrophotometric study In order to study the catecholase activity of the complex 1, 3,5-DTBC with two bulky t-butyl substituents on the ring and low quinone-catechol reduction potential has been chosen as substrate.This makes it easily oxidized to the corresponding o-quinone, 3,5-DTBQ which is highly stable and shows a maximum absorption at401 nmin methanol. Solution of 1was treated with 100 equivalentsof 3,5-DTBC under aerobic conditions. The repetitive UVeVisspectral scanwas recorded in pure MeOH and MeCN (Figs. 3 and 4).Spectral bands at 264 and 496 nm appear in the electronic spectrumof complex 1, whereas 3,5-DTBC shows a single band at282 nm. After addition of 3,5-DTBC, the time dependent spectral scanshows very smooth growing of quinone band at 400 nm, as reportedby Krebs et al. [23], indicates the formation of the respectivequinone derivative, 3,5-DTBQ which was purified by column chromatography. The product obtained from each solvent wasisolated in high yield (65% and 70%) by slow evaporation of theeluant and was identified by measuring melting point (~110 C). |
70% | With C32H32Cl2Cu2N2O2S2; oxygen In methanol at 25℃; for 6h; | 3.4 Catecholase activity of 1:spectrophotometric study In order to study the catecholase activity, 3,5-ditertiarybutylcatechol (3,5-DTBC) was chosen as a substrate. It can easily be oxidized to the corresponding quinone 3,5-ditertiarybutylquinone (3,5-DTBQ) which is very stable because the low quinine catechol reduction potential. Before proceeding the detail kinetic experiment we have done simple repetitive UV-VIS scan for 6h by adding the mixture of the catalyst (1×10-4M concentration) and 100 equivalent amount of the substrate 3,5-DTBC in methanol and acetonitrile solvents (Figs. 3 and 4 ). 3,5-DTBC shows a single band at 282nm (inset to Fig. 3). Characteristic peaks of 3,5-DTBQ, which is an oxidation product of 3,5-DTBC by aerial oxygen in presence of 1, appears at 398nm in methanol and 401nm in acetonitrile are very close or same to the reported value of 401nm [16]. The quinone was separated and purified by column chromatography and the product was isolated with high yield (70%). The quinine is characterised by melting point measurements with the value 110°C [17]. In order to find out the reaction rate between 3,5-DTBC and 1, the reaction kinetics was studied and observed that the time dependent change in absorbance was at a wavelength of 398nm in methanol and 401 in acetonitrile. Gradually the colour of the solution was turned deep brown that indicates that the gradual conversion of 3,5-DTBC to 3,5-DTBQ. In methanol the difference in absorbance ΔA at 398nm was plotted against time to calculate the initial rate for that particular catalyst to substrate concentration ratio (Fig. 5 ). A first-order catalytic reaction was observed, with initial rate 5.08×10-3min-1. But in acetonitrile the same was done at 401nm, the reaction was also of first order (Fig. 6 ) with initial rate 3.25×10-5min-1. 3.4.1 Enzyme kinetics study Enzymatic kinetic experiments were performed UV-Vis spectrophotometrically thermostated at 25°C with the complex, and the substrate 3,5-DTBC in MeOH. 0.04ml of each complex solution, with a constant concentration of 1×10-4M, was added to 2ml of 3,5-DTBC of a particular concentration (varying its concentration from 1×10-3M to 1×10-2M) to achieve the ultimate concentration of the complex as 1×10-4M. The conversion of 3,5-DTBC to 3,5-DTBQ was monitored with time at a wavelength of 398nm for solutions in MeOH and 401nm in acetonitrile. The rate for each concentration of the substrate was determined by the initial rate method. The rate versus concentration of substrate data were analyzed on the basis of Michaelis-Menten approach of enzyme kinetics to get the Lineweaver-Burk (double reciprocal) plot as well as the values of the various kinetic parameters Vmax (maximum velocity), KM (Michaleis-Menten constant) and Kcat (Turn over number). The observed rate vs. [substrate] plot along with Lineweaver-Burk plot in methanol and acetonitrile solutions are given respectively in Figs. 7 and 8 . The turnover numbers (Kcat) are calculated as 4.02×103h-1 in methanol and 9.57×103h-1 in acetonitrile. |
70% | With oxygen; pyrographite In 5,5-dimethyl-1,3-cyclohexadiene at 120℃; for 24h; | |
70% | With oxygen; [Cu(μ-Cl)(4-oxo-4H-chromene-3-carbaldehyde-4(N)-ethylthiosemicarbazone)]2Cl2 In methanol at 25℃; for 1.5h; | |
67% | With C10H12N2O4V(1-)*H(1+); oxygen In methanol for 6h; | |
64% | With Py2CuCl2; PyCuClOCH3; oxygen In pyridine; methanol for 2h; | |
62% | With C18H14N4O4(4-)*2V(5+)*4O(2-)*2Na(1+)*8H2O In acetonitrile for 6h; | |
60% | With N5-ethyl-2-hydroperoxy-3-methyllumiflavine; potassium-t-butoxide In <i>tert</i>-butyl alcohol at 30℃; | |
60% | With 1-methyl-1,3-dihydro-indol-2-one In dichloromethane at 55℃; for 24h; | |
54% | With C48H44Cu4N10O14(2+)*2CH3O(1-) In methanol at 25℃; for 1h; | Catechol oxidation 3,5-Di-tert-butyl catechol (43 mg,0.192 mmol) dissolved in methanol (2 mL) was added to methanol/HEPES buffer (pH 8.2) solution of R-Cu2+ (2.5 mg, 0.002 mmol)(3 mL) (100:1 ratio of substrate and catalyst). The mixture was stirred for 1 h, and the solvent was removed under reduced pressure. The residue was extracted with CH2Cl2 (3 10 mL). The organic fractions were combined, filtered through Celite, and dried over Na2SO4. The solvent was removed under reduced pressure, and the residue (36 mg), as analyzed by 1H NMR spectroscopy in CDCl3 is a mixture of the product 3,5-dtbq (54%) and the substrate 3,5-dtbc (46%). Yield of 3,5-dtbq relative to the starting 3,5-dtbc = 46%. |
53% | With oxygen; 2,3-dihydro-2,2,2-triphenylphenanthro[9,10-d]-1,3,2-λ5-oxazaphosphole In methanol at 60℃; for 5h; Schlenk technique; | |
52% | With oxygen at 50℃; for 12h; chemoselective reaction; | |
51% | With potassium superoxide; Etamon In N,N-dimethyl-formamide at 20℃; | |
43% | With triethylamine; copper(II) bromide In 1,2-dichloro-ethane at 25℃; for 3h; Schlenk technique; | |
40% | With benzenetellurinyl acetate In chloroform for 12h; Heating; | |
35% | With dihydrogen peroxide; ferric acetate; glacial acetic acid; 3-chloro-benzenecarboperoxoic acid for 2h; | |
With dinuclear Cu(I); oxygen for 24h; Ambient temperature; other tyrosinase moldels; | ||
With oxygen; copper chloride (II) In pyridine for 24h; Ambient temperature; other copper reagents, other solvents; | ||
With dihydrogen peroxide In acetonitrile at 5℃; for 0.166667h; various peroxides; | ||
With copper(I) tetrakis(acetonitrile) hexafluorophosphate; 3,6,9,16,19,22-hexaazatricyclo{22.2.1.1(11,14)}octacosa-1(26),2,9,11,13,15,22,24-octaene; oxygen In methanol; acetonitrile for 2h; | ||
With <Cu(me-ox)>(PF6)2; oxygen; triethylamine In methanol at 15℃; var. catalysts, other aromatic; | ||
With oxygen In dimethyl sulfoxide at 25℃; for 5h; further catalysts; also 4-methylcatchol; | ||
different catalysts; stoichiometric conditions as well; | ||
With oxygen In methanol at 25℃; for 1.16667h; investigation of catalytic activity; different catalysts and reaction times; | ||
With oxygen In methanol at 25℃; | ||
With lead(IV) dioxide | ||
With dihydrogen peroxide | ||
With o-tetrachloroquinone | ||
Multistep reaction; | ||
With cerium (IV) sulfate; sulfuric acid In methanol; chloroform for 2h; ice methanol cooled solution; | ||
With oxygen In toluene for 0.5h; Yield given; | ||
With oxygen; copper chloride (II) In pyridine for 24h; Ambient temperature; Yield given; | ||
With oxygen In methanol | ||
With argon; oxygen; mesoporous silica | ||
With sodium (meta)periodate In acetate buffer at 20℃; | ||
With oxygen In methanol | ||
With oxygen In propan-2-one at -60℃; | ||
100 % Spectr. | With [Cu(N,N,N',N'-tetramethylethylenediamine)OH]2(ClO4)2; oxygen In acetonitrile at 25℃; | |
With oxygen In dichloromethane at 20℃; | ||
With copper(II)-Ac-His-His-Gly-His-OH; oxygen In methanol; lithium hydroxide monohydrate at 24.85℃; | ||
With air; dicopper(II) organic In methanol at 25℃; | ||
With Cu[p-tert-butyl-calix[4]arene-1,3-(OCH2CO2H)2]pyridine; oxygen In methanol; chloroform for 16h; | ||
With air; di-Cu2+-dinuclear aminopeptidase from Streptomyces griseus; HEPES buffer at 25℃; | ||
With Cu2{2-[(2-OH-5-Me-benzyl)amino]cyclohexane-1-CO2H}(H2O)2 In methanol at 25℃; | ||
With oxygen In methanol at 25℃; | ||
With oxygen In methanol at 20℃; for 15h; | ||
With meso-pentafluoro[26]hexaphyrin(1.1.1.1.1) In chloroform-d1 at 20℃; | ||
With oxygen In methanol | ||
With air; dimanganese(IV) compound In dichloromethane at 20℃; | ||
In methanol at 25℃; | ||
98 % Chromat. | With copper(ll) acetate; oxygen; benzene-1,2-diol In acetonitrile at 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With nitric acid In acetic acid | 15 4,6-di-tert-Butyl-3-nitrocyclohexa-3,5-diene-1,2-dione Example 15 4,6-di-tert-Butyl-3-nitrocyclohexa-3,5-diene-1,2-dione To a solution of 3,5-di-tert-butylcyclohexa-3,5-diene-1,2-dione (4.20 g, 19.1 mmol) in acetic acid (115 mL) was slowly added HNO3 (15 mL). The mixture was heated at 60° C. for 40 min before it was poured into H2O (50 mL). The mixture was allowed to stand at room temperature for 2 h, then was placed in an ice bath for 1 h. The solid was collected and washed with water to provide 4,6-di-tert-butyl-3-nitrocyclohexa-3,5-diene-1,2-dione (1.2 g, 24%). 1H NMR (400 MHz, DMSO-d6) δ 6.89 (s, 1H), 1.27 (s, 9H), 1.24 (s, 9H). |
24% | With nitric acid In acetic acid at 60℃; for 0.666667h; | 15 4,6-di-tert-Butyl-3-nitrocyclohexa-3,5-diene-1,2-dione To a solution of 3,5-di-tert-butylcyclohexa-3,5-diene-1,2-diose (4.20 g, 19.1 mmol) in acetic acid (115 mL) was slowly added HNO3 (15 mL). The mixture was heated at 60° C. for 40 min before it was poured into H2O (50 mL). The mixture was allowed to stand at room temperature for 2 h, then was placed in an ice bath for 1 h. The solid was collected and washed with water to provide 4,6-di-tert-butyl-3-nitrocyclohexa-3,5-diene-1,2-dione (1.2 g, 24%). 1H NMR (400 MHz, DMSO-d6) δ 6.89 (s, 1H), 1.27 (s, 9H), 1.24 (s, 9H). |
With nitric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.7% | for 6h; Heating; | |
59% | In methanol at 20℃; | 4.2. All N,N-disubstituted o-aminophenols were synthesized using the single general procedure General procedure: A solution of 3,5-di-tert-butyl-o-benzoquinone (2.2 g; 0.01 mol) in MeOH (50 mL) and three-fold excess of dried amine was stirred at room temperature. When the cherry-red solution turned colorless o-aminophenol was formed. Upon concentration of the reaction mixture to 15-20 mL colorless crystals was collected by filtration and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.1% | With water for 5h; Heating; | |
62% | In methanol at 20℃; | 4.2. All N,N-disubstituted o-aminophenols were synthesized using the single general procedure General procedure: A solution of 3,5-di-tert-butyl-o-benzoquinone (2.2 g; 0.01 mol) in MeOH (50 mL) and three-fold excess of dried amine was stirred at room temperature. When the cherry-red solution turned colorless o-aminophenol was formed. Upon concentration of the reaction mixture to 15-20 mL colorless crystals was collected by filtration and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium <i>tert</i>-butylate In <i>tert</i>-butyl alcohol at 30℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In nitromethane for 24h; Ambient temperature; | |
1: 85% 2: 15% | With C34H24Cl4Cu2FeN10O4(1-)*C8H20N(1+); oxygen; sodium hydroxide In methanol at 25℃; for 6h; | |
1: 76% 2: 24% | With [Co(3-hydroxy-2-quinoxalinecarboxylato)2(H2O)2]*2H2O; dihydrogen peroxide; sodium dodecyl-sulfate; potassium hydroxide In water at 50℃; for 4h; | 1 At room temperature,Was added to a 10 ml three-necked flask equipped with a condenser and a thermometer2,4-di-tert-butylphenol(206 mg, 1 mmol),Potassium hydroxide (56 mg, lmmol) and sodium dodecyl sulfate (SDS, 29 mg, lmmol) were added and then added5 mL of pure water, stirred and the cobalt complex (0.02 mmol) prepared in Example 1 was added as a catalyst. Heated to 50 ° C with stirring,The aqueous solution of H202 having a mass percentage of 30% was slowly dropped into the above mixed solution with a 10 μ1 syringe, and the mixture was added every 15 minutesInto 10μ1, a total of 20μ1 drop, reaction 4h (from the beginning of the drop of H202 aqueous solution began to stop) after the stop. Prepared by TLC methodThe reaction product was separated on a thin layer of silica gel. The results showed that the conversion of 2,4 - di - tert - butyl phenol was 100%The yield of 2 '- dihydroxy - 3,3', 5,5 '- tetra - tert - butylbiphenyl (TBBP) was 76% and the yield of benzoquinone was 24%. |
1: 63% 2: 7% | In acetonitrile for 24h; Ambient temperature; other Co-complexes, other solvents; | |
1: 6% 2: 11% | In methanol for 24h; Ambient temperature; | |
Multistep reaction; | ||
With [copper(I)(NC5H4(CH2)2NCHC(CH3)3)(acetonitrile)2]PF6; oxygen; triethylamine In dichloromethane | ||
With hydrogenchloride; C19H27CuN5(1+)*F6P(1-); oxygen In dichloromethane for 1h; | ||
With tetrakis(actonitrile)copper(I) hexafluorophosphate; oxygen; N-ethyl-N,N-diisopropylamine In dichloromethane at 23℃; for 1h; Molecular sieve; | ||
1: 15 %Chromat. 2: 85 %Chromat. | With C34H22Cl4Cu2FeN10O4(1-)*C8H20N(1+); oxygen; sodium hydroxide In methanol at 25℃; for 6h; | |
With [Cu(MeCN)2(2-[(1H-pyrazol-1-yl)methyl]pyridine)]PF6; oxygen; triethylamine In dichloromethane at 20℃; for 6h; Glovebox; | ||
With C16H22CuN6(1+)*F6P(1-); oxygen; triethylamine In dichloromethane at 20℃; for 5h; | ||
With C15H23CuN7(1+)*ClO4(1-); oxygen; triethylamine In dichloromethane at 20℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With tetrakis(actonitrile)copper(I) hexafluorophosphate; N,N'-di-tert-butylethylenediamine; oxygen; In dichloromethane; phenol; at 20℃; under 760.051 Torr; for 4h;Inert atmosphere; | Representative Procedure: 12 A flame-dried, 25 mL Radley tube, equipped with a Teflon-coated stir barand a rubber septum, was charged with 3 (206.3 mg, 1.0 mmol, 1.0 equiv) and additive (if applicable, cf.Table S3). The reaction vessel was then purged with a steady stream of N2 for 2 min prior to the additionof dry and degassed CH2Cl2 (8.0 mL). A separate, flame-dried test tube (16 x 125 mL) was charged with[Cu(CH3CN)4]PF6 (cf. Table S3), N,N?-di-tert-butylethelenediamine (cf. Table S3), and CH2Cl2 (2.0 mL)to afford a homogeneous, pink solution. This solution was then added to the Radley tube via syringe toafford a final volume of 10.0 mL and a concentration of 0.1 M with respect to the phenol. The rubberseptum was then rapidly removed and replaced with a Radley cap, which was connected to a tank of O2and pressurized to 1 atm. Under a constant O2 pressure (1 atm), the reaction was vented 3 times for 10 s toeliminate N2. The reaction mixture was then stirred at room temperature for 4 h, depressurized by opening12 Procedure was adapted from Esguerra, K. V. N.; Fall, Y.; Lumb, J.-P. Angew. Chem. Int. Ed. 2014, 53, 5877-5881S13to the atmosphere and quenched by the addition of NaHSO4 (20 mL, 10% by weight aqueous solution).The phases were then separated, and the aqueous phase was extracted with CH2Cl2 (3 x 20 mL). Thecombined organic fractions were then dried over MgSO4, filtered and concentrated in vacuo to afford aresidue which was analyzed directly by 1H NMR.Analytical data for compound 2: 1H NMR (500 MHz, CDCl3) delta 6.92 (d, J = 2.3 Hz, 1H), 6.18 (d, J = 2.4Hz, 1H), 1.24 (s, 9H), 1.20 (s, 9H). Analytical data matches that reported in the literature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium fluoride In acetonitrile for 1h; Ambient temperature; | |
83% | With potassium carbonate In acetonitrile | XII 4,6-Di-tert-butyl-2-triethylsiloxy-2-trifluoromethyl-3,5-cyclohexadien-1-one EXAMPLE XII 4,6-Di-tert-butyl-2-triethylsiloxy-2-trifluoromethyl-3,5-cyclohexadien-1-one The procedure of Example V was repeated using a mixture of 176 mg (0.80 mmol) of 3,5-di-tert-butyl-1,2-benzoquinone, 147 mg (0.80 mmol) of triethyltrifluoromethylsilane, 22 mg (0.16 mmol) of potassium carbonate, and 1 mL of acetonitrile at 25 C for 24 hours. PTLC afforded 269 mg (83% yield) of 4,6-di-tert -butyl-2-triethylsiloxy-2-trifluoromethyl-3,5-cyclohexadien-1-one as a yellow liquid: 1 H NMR (CDCl3) δ 0.35-1.10 (m, 15H), 1.16 (s, 3H), 1.23 (s, 3H), 5.85 (d, 1H, J=2 Hz), 6.84 (d, 1H, J=2 Hz); 19 F NMR (CDCl3, relative to CFCl3) -80.0 ppm (s); IR (neat) 2955, 2909, 2874, 1689, 1459, 1366, 1270, 1244, 1179, 1143, 1072, 1033, 998, 890, 831, 810, 743, 695 cm-1; mass spectrum (70 eV) m/z (relative intensity) 404 (29, M+), 389 (20), 375 (79, M-C2 H5), 57 (100). |
83% | With potassium carbonate In acetonitrile | X 4,6-Di-tert-butyl-2-Triethylsiloxy-2-trifluoromethyl-3,5-cyclohexadien-1-one EXAMPLE X 4,6-Di-tert-butyl-2-Triethylsiloxy-2-trifluoromethyl-3,5-cyclohexadien-1-one The procedure of Example III was repeated using a mixture of 176 mg (0.80 mmol) of 3,5-di-tert-butyl-1,2-benzoquinone, 147 mg (0.80 mmol) of triethyltrifluoromethylsilane, 22 mg (0.16 mmol) of potassium carbonate, and 1 mL of acetonitrile at 25° C. for 24 hours. PTLC afforded 269 mg (83% yield) of 4,6-di-tert-butyl-2-triethylsiloxy-2-trifluoromethyl-3,5-cyclohexadien-1-one as a yellow liquid: 1 H NMR (CDCl3)δ0.35-1.10 (m, 15H), 1.16 (s, 3H), 1.23 (s, 3H), 5.85 (d, 1H, J =2 Hz), 6.84 (d, 1H, J=2 Hz); 19 F NMR (CDCl3, relative to CFCl3) -80.0 ppm (s); IR (neat) 2955, 2909, 2874, 1689, 1459, 1366, 1270, 1244, 1179, 1143, 1072, 1033, 998, 890, 831, 810, 743, 695 cm-1; mass spectrum (70 eV) m/z (relative intensity) 404 (29, M+), 389 (20), 375 (79, M-C2 H5), 57 (100). Anal. Calcd. for C21 H35 F3 O2 Si: C, 62.34; H, 8.72. Found: C, 62.46; H, 8.69. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 20% 2: 18% 3: 38% | With 2,5-bis(1,1-dimethylethyl)-1,4-benzenediol; oxygen In tetrahydrofuran at 25℃; for 96h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 3,5-di-tert-butyl-o-benzoquinone; 2-amino-4,6-di-tertbutylphenol In pyridine; methanol for 2h; Reflux; Stage #2: With potassium hydroxide; potassium hexacyanoferrate(III) In diethyl ether; water | Synthesis of redox-active phenox-imQ was carriedout using an original procedure which is a modificationof published earlier [27]. 4,6-Di-tert-butyl-oaminophenol(3.50 g, 15.8 mmol) [28] and 3,5-di-tertbutyl-o-benzoquinone (3.47 g, 15.8 mmol) wereplaced in a flask with a stirrer and dissolved in methanol(50 mL). After dissolution the reaction mixtureturned intensively violet. Pyridine (5 mL) was addedto the resulting solution, and the reaction mixture wasrefluxed with an air reflux condenser for 2 h. The reactionafforded a mixture of the oxidized and reducedforms of phenox-imQ. The dropwise addition of waterto the reaction mixture resulted in the precipitation ofa dark blue substance. The dry residue was dissolved inEt2O, and the solution was transferred to a separatingfunnel. A saturated aqueous solution of K3Fe(CN)6(20 g) and KOH (1 g) was added to the obtained mixture.The resulting reaction mixture was vigorouslyshaken. The oxidation process was monitored by thinlayerchromatography (TLC) using a hexane-ethylacetate (1 : 30) system as an eluent. The disappearanceof one of two blue spots on the chromatogram servedas the indication of the reaction end. The obtainedproduct was crystallized from hexane at -18°. Theformed dark blue crystals of phenox-imQ weredecanted from the mother liquor. The yield was 5.26 g(78%). The spectroscopic data of the synthesizedcompound correspond to the published data [27, 29]. |
With ammonia; water 1.) MeOH; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | In toluene for 10h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With [Cu3(N2,N2'-bis-[(1-butylbenzimidazol-2yl)methyl]biphenyl-2,2'-dicarboxamide)3(NO3)3]3NO3*9H2O; oxygen; In acetonitrile; at 60℃; for 15h; | General procedure: Oxidation of 2,4,6-tri-tert-butyl phenol, 2-amino-5-methylphenol, 2-amino-4-tert-butyl phenol were studied homogeneouslyusing Cu(II) metallatriangles as catalyst in acetonitrile (Scheme 2).The oxidation of 2,4,6-tri-tert-butyl phenol was studied under continuousslow passage of molecular oxygen for a time duration of15 h at 60 C. For the oxidation of 2-amino-5-methyl phenol and2-amino-4-tert-butyl phenol, a solution of these was saturatedwith molecular oxygen and subsequently, the respective phenolswere added and the resultant reaction mixture was stirred at roomtemperature for 4.5 h. The ratio of catalyst:substrate was fixed to1:30 for each reaction. The progress of the reaction was monitoredby TLC (5% ethyl acetate in petroleum ether). After completion ofreaction (as monitored by TLC), reaction mixture was evaporatedto dryness on a rotatory evaporator at reduced pressure and theresidue was extracted with 10 ml diisopropyl ether. The organiclayer was dried over Na2SO4 and evaporated to get the crude compound.This which was further purified by column chromatographyusing 2% ethyl acetate in petroleum ether as eluent for theisolation of 3,5-di-tert-butyl-1,2-diquinone and 2-amino-5,8-dimethyl-4,4-dihydrophenoxazin-3-one; while petroleum etherwas used as the eluent for the isolation of 2,8-di-tert-butyl-10Hphenoxazine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With trifluoroacetic acid In benzene for 14h; Reflux; Dean-Stark; | 4.2.3. Methyl-2-[3,5-di-tert.-butyl)-(20-hydroxyphenyl)amino]benzoate (5a) Benzene solution (30 mL) of 1.1 g (5.0 mmol) of 3,5-di-(tert.-butyl)-1,2-benzoquinone and 1.1 mL (7.5 mmol) of methyl ester of2-aminobenzoic acid contained 0.05 mL of triuoroacetic acid wasreuxed for 2 h and then for 12 h using Dean-Stark apparatus. Thereaction mixture was puried by passing through a SiO2 chro-matographic column (l 25 cm, d 3.0 m, benzene) to select abright yellowish-green fraction ( 380 nm) with Rf 0.75. Thesyrup-like product gradually crystallized at room temperatureduring 2e3 days and was recrystallized from methanol to give1.35 g (76%) of yellow crystals of 7a with m.p. 106e108. IR (KBr, n,m1): 3402 (-H), 3330 (NeH) 2953, 2866 (CeH), 1677 ( O).1 NMR (d, ppm, DMSO-d6): 8.88 s (1H, NH), 8.33 s (1H, ),7.86 d (J 8.0, 1.5 Hz, 1H, 6), 7.32 m (1H 4), 7.09 d (J 2.2 Hz, 1H,60), 7.04 d (J 2.2 Hz,1H, 40), 6.71e6.61 m (2H, 3-5), 2.50 m (3H,),1.39 s (9, 30-t-Bu), 1.23 s (9H, C50-t-Bu); mz: 355 (100%)[M]; Found: C, 74.34; H, 8.25; N, 3.92. C22H29NO3 requires C, 74.33;H, 8.22; N, 3.94. The data on IR,1H NMR, mass-spectra are collectedin SI (Figs. S17eS19). |
39% | With 3,5-Di-tert-butylcatechol at 135 - 140℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In 2,2,2-trifluoroethanol at 20℃; for 1h; | |
53% | In methanol at 20℃; | 4.2. All N,N-disubstituted o-aminophenols were synthesized using the single general procedure General procedure: A solution of 3,5-di-tert-butyl-o-benzoquinone (2.2 g; 0.01 mol) in MeOH (50 mL) and three-fold excess of dried amine was stirred at room temperature. When the cherry-red solution turned colorless o-aminophenol was formed. Upon concentration of the reaction mixture to 15-20 mL colorless crystals was collected by filtration and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In methanol at 20℃; | 4.2. All N,N-disubstituted o-aminophenols were synthesized using the single general procedure General procedure: A solution of 3,5-di-tert-butyl-o-benzoquinone (2.2 g; 0.01 mol) in MeOH (50 mL) and three-fold excess of dried amine was stirred at room temperature. When the cherry-red solution turned colorless o-aminophenol was formed. Upon concentration of the reaction mixture to 15-20 mL colorless crystals was collected by filtration and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | In methanol at 20℃; | 4.2. All N,N-disubstituted o-aminophenols were synthesized using the single general procedure General procedure: A solution of 3,5-di-tert-butyl-o-benzoquinone (2.2 g; 0.01 mol) in MeOH (50 mL) and three-fold excess of dried amine was stirred at room temperature. When the cherry-red solution turned colorless o-aminophenol was formed. Upon concentration of the reaction mixture to 15-20 mL colorless crystals was collected by filtration and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 23% 2: 14% | With C38H50Cl2CuN4O2*H2O; oxygen In methanol at 20℃; for 5h; | Oxidation of 2,4,6-tri-tert-butylphenol and isolation of reaction products 1 mL of 2,4,6-tri-tert-butylphenol solution (85 mg, 324 mM) inmethanol was mixed with 2 mL of copper complex solution(6 mg, 4 mM). The solution was exposed to a slow stream ofmolecular oxygen for twenty minutes and contents stoppered.The solution was stirred at room temperature for 5 h. Theformation of oxidation products was monitored by TLC by using100% toluene solvent system. A TLC of the reaction mixture onsilica gel gives two spots with 2,4-dinitrophenylhydrazine. Twoproducts were found at Rf = 0.20 (A) and 0.69 (B). These wereisolated using preparative TLC. The yield of the products was23% (A) and 14% (B). |
With C19H22CuN6O3(3+); oxygen In toluene for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 42% 2: 11% | With trifluoroacetic acid In methanol at 20 - 40℃; | For the synthesis of 8,8-dimethyl-7,8,9-trihydro-2,4-di-tert-butylbenzo[2,3]oxonino[4,5-b]quinoxaline-6-one (12) and 3-[2-(2-hydroxy-3,5-di-tert-butylphenylamino)]-5,5-dimethyl-2-cyclohexen-1-one (13), 3-(2-aminophenylamino)-5,5-dimethyl-2-cyclohexen-1-one (10) (0.46 g, 2 mmol) was dissolved in (5 ml) at room temperature. Next, 3,5-di-tert-butyl-1,2-benzoquinone (11) (0.44 g, 2 mmol) was added. The mixture was heated to ∼40 ° and treated with CF3COOH (two drops) after dissolution of the quinone (about 2 min). The reaction mixture became lighter during 1 min and then gradually darkened. Precipitation started after 8-10 min on scratching using a glass rod. The solution and residue were cooled after 1 h; the residue was filtered, washed with a little and petroleum ether and dried. The yield of 12a was 0.22 g. The methanol filtrate was treated with H2O and the residue obtained was filtered, dried, and extracted with Et2O (5 ml). The residue was filtered once more, washed with Et2O and dried. The yield of 13 was 11% (0.1 g). The residue was purified by recrystallization from MeOH or CH3CN. Mp 201-203 ° (13 was recrystallised from CH3CN twice). An additional amount of 12a was obtained from the ether filtrate and the remainder was transferred to a chromatographic column (Al2O3, eluent-CHCl3) and the head fraction separated. The solvent was evaporated and the obtained oil was triturated with CH3CN and the residue filtered. The total yield of colorless crystalline product 12a was 42% (0.36 g). Mp 173-175 ° (12a was recrystallized from MeOH). Compound 12a was soluble in CHCl3, and a solvate with CHCl3 (1:1) was obtained on cooling and scratching with a glass rod. The solvate stoichiometry was established by elemental analysis. Compound 12a. IR (ATR): ν 2957 m (t-Bu), 1743 s (CO), 1200 s, 1174 s, 1100 s (C-O) cm-1.1H NMR (CDCl3, 600 MHz): δ (ppm) 1.08 and 1.23 (both s, 6H, CH3), 1.33 and 1.37 (both s, 18H, t-Bu), 2.08 (dd, 1H, C(7)H2, 2J = 12.9 Hz, 4J = 1.2 Hz), 2.33 (d, 1H, C(7)H2, J = 12.9 Hz), 2.80 (dd, 1H, C(9)H2, 2J = 12.3 Hz, 4J = 1.2 Hz), 2.88 (d, 1H, C(9)H2, J = 12.9 Hz), 7.22 (d, 1H, C(1)H, J = 2.1 Hz), 7.57 (d, 1H, C(3)H, J = 2.1 Hz), 7.71 (m, 2H, C(12)H, C(13)H), 8.05 (m, 2H, C(11)H, C(14)H). MS (EI, 70 eV): m/z 430 [M]+. Anal. Calcd for C28H34N2O2: C, 78.10; H, 7.96. Found: C, 77.93; H, 8.15. Compound 13. IR (ATR): ν 3392 m, 3258 m, 3200 br r (OH, NH), 2955 m (t-Bu), 1596 m, 1552 s, 1532 s (arom) cm-1. 1H NMR (CDCl3, 600 MHz): δ (ppm) 1.04 (s, 6H, CH3), 1.23 (s, 9H, t-Bu(11)), 1.40 (s, 9H, t-Bu(10)), 2.15 (s, 2H, C(6)H2), 2.28 (s, 2H, C(4)H2), 5.25 (s, 1H, C(2)H), 5.33 (s, 1H, OH), 5.98 (s, 1H, N(I)H), 6.35 (s, 1H, N(II)H), 6.62 (dd, 1H, C(3')H, 3J = 8.4 Hz, 4J = 1.2 Hz), 6.80 (t, 1H, C(5')H, J = 7.5 Hz), 6.93 (d, 1H, C(6)H, J = 2.4 Hz), 7.09 (m, 2H, C(6')H, C(4')H), 7.17 (d, 1H, C(4)H, J = 2.4 Hz). MS (EI, 70 eV): m/z 434 [M]+. Anal. Calcd for C28H38N2O2: C, 77.38; H, 8.81. Found: C, 77.54; H, 8.75. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | In n-heptane at 20℃; for 0.5h; | 3.2 3.2 Preparation of 2,4-di-tert-butyl-6-(pyridine-2-yl-methylamino)phenol (HLAph) To a solution of 3,5-DTBQ (1 mmol, 0.22 g) in n-heptane (9 ml) was added 2-(aminomethyl) pyridine (1 mmol, 0.108 ml), followed by stirring for 30 min at room temperature. A yellow precipitate was formed, collected by filtration and then washed with cold n-heptane. The solid material was air-dried and crystallized in a 1:1 dichloromethane/n-hexane mixture (0.2 g, 65%). Anal. Calc. (found) for C20H26N2O: C 77.38 (77.29), H 8.44 (8.26), N 9.02 (9.06). IR (KBr, cm-1): 688, 751, 793, 871, 915, 959, 1030, 1143, 1193, 1246, 1306, 1362, 1473, 1586, 1623, 2869, 2902, 2956, 3059, 3347. 1H NMR (400 MHz, CDCl3, Me4Si) δH: 1.359(s, 9H), 1.489(s, 9H), 7.292(s, 2H), 7.354(q, 1H), 7.853(q, 2H), 8.264(t, 1H), 8.746(t, 1H), 8.899(s, 1H). 13C NMR (100 MHz, CDCl3, Me4Si) δC: 29.42, 31.59, 34.62, 34.99, 76.71, 77.03, 77.34, 110.38, 121.23, 124.55, 125.09, 135.51, 136.73, 141.69, 149.74, 154.58, 155.98. M.p.: 135-138 °C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With potassium fluoride; 18-crown-6 ether In tetrahydrofuran at 0 - 20℃; for 2h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique; | 4.5.12 Preparation of 12 A solution of 0.191 g of 9 (0.85mmol) was added slowly to a solution of 0.320 g of LNN1SnCl (0.85mmol) in 30 mL of THF at room temperature. The green reaction mixture was evaporated in vacuo, washed with hexane and finally dried under vacuum. 0.340 g of 12 (0.57 mmol) was obtained (yield 67%). The aliphatic part of the 1H NMR spectrum is rather complex with some signals being overlapped by signals of complexed THF. 1H NMR (500 MHz, C6D6, 295 K) δ: 7.22 (t, 1H, J=7.6Hz, ArH(4)); 7.14 (d, 1H, J=7.9Hz, ArH(6)); 7.11 (br s, 1H, ArH(4′)); 6.87 (m, 2H, ArH(3,6′)); 6.74 (m, 1H, ArH(5)); 3.67, 2.38 (anisochronous signals, AX spin system, Δδ=648Hz, 2H, NCH2); 1.47 (br s, 6H, N(CH3)2); 1.33 (s, 18H, C(CH3)3); 0.34 (s, 9H, Si(CH3)3). 119Sn NMR (134 MHz, C6D6, 295 K) δ:-471. Anal. found: C 52.5, H 7.0, Cl 6.1, N 4.61%; Calcd for C26H41ClN2O2SiSn: C 52.41, H 6.94, Cl 5.59, N 4.70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | With acetic acid at 65 - 67℃; for 30h; | |
12% | In acetic acid at 65 - 67℃; for 30h; | (2E)-4,6-Di(tert-butyl)-2-(8-methoxyquinolin-2(1H)-ylidene)cyclohepta-4,6-diene-1,3-dione (4a). A mixture of 8-methoxy-2-methylquinoline (3a) (0.87 g, 5 mmol) and 3,5-di(tert-butyl)-1,2-benzoquinone (2) (2.20 g, 10 mmol) in acetic acid (5 ml) was maintained at 65-67°C for 30 h with monitoring by thin-layer chromatography. At the end of the reaction, the cooled mixture was diluted with cold water (250 ml) and extracted with CH2Cl2 (3×30 ml). The organic fraction was dried over sodium sulfate and evaporated. The product was separated by chromatography on an alumina column using 1:1 hexane-CH2Cl2 as the eluent, and the yellow fraction with Rf 0.50-0.65 was collected. After distilling off the solvent, the product was recrystallized from 2-propanol. Yield 0.23 g (12%). Yellow crystals. Mp 176-177°. IR spectrum, ν, cm-1: 1391, 1442, 1459, 1475, 1509, 1568, 1607, 1617 (C=O), 1643 (C=O), 3015-3110 (N-H). 1H NMR spectrum, δ, ppm (J, Hz): 1.22 (9, s, 6-(3)3); 1.35 (9, s, 4-(3)3); 4.10 (3, s, 3); 6.62 (1, d, J = 3.1, H-7); 6.65 (1, d, J = 3.1, H-5); 7.07 (1, d, J = 0.8, H-7'); 7.29-7.38 (2, m, H-5',6'); 8.01 (1, d, J = 9.4, H-4'); 8.17 (1, d, J = 8.7, H-3'); 19.32 (1, s, N). 13C NMR spectrum is given in Table 2. Mass spectrum, m/z (Irel, %): 391 [M]+ (3), 373 [M-CO]+ (25), 320 (15), 306 (11), 292 (5), 234 (4), 140 (6), 91 (16), 57 (72), 41 (100). Found, %: 76.25; H 7.38; N 3.55. C25H29NO3. Calculated, %: 76.70; H 7.47; N 3.58. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With oxygen; mesoporous silica In dichloromethane at 25℃; for 4.5h; | 3.3. General Procedure for P1/Silica-gel Combined Catalyst Catalyzed Aerobic Oxidation of Various Dihydroxy Arenes General procedure: In a two-neck 100 ml round bottomed flask connected tomolecular oxygen balloon (1.0 atm) and containing dihydroxyarene (0.1 mmol), P1 (100 mg, 0.1 mmol/g loading)and 250 mg silica-gel, a 3.0 mL of CH2Cl2 was injected and the reaction mixture was stirred at room temperature and followed by TLC until the starting material had completely converted to quinone. The quinone product was extracted with CH2Cl2 or ether and was obtained under reduced pressure.The further purification of most of the quinone product was not necessary. The P1/silica-gel combined catalyst was washed several times with ether or CH2Cl2 until it became completely clean and dried under vacuum to be ready for the next cycle. |
With [Cu3(μ-OH)(μ-diphenylphosphinate)3(μ-hexafluoroacetylacetonate)3]; oxygen In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In acetonitrile at 20℃; for 0.5h; | 2.2.1. Synthesis of HLBAP A synthesis of ligand precursor HLBAP (Scheme 6) was already previously described [16, 36]. A solution of 3,5-DTBQ (3,5-di tertbutyl quinone; 0.22 g, 1.0 mmol) in acetonitrile (4 mL) was prepared,to which 2-aminobenzyl amine (0.122 g, 1.0 mmol) was added. The reaction solution was stirred for 30 min at the room temperature in the presence of air. The yellow precipitate of HLBAP was filtered off and dried in air. (0.278 g, 85% yield). Anal. Calcd. for C21H28N2O (324.46 g/mol) C,77.74; H, 8.70; N, 8.63%. Found: C, 76.93; H, 8.55; N, 8.48%. 1H NMR(400 MHz, CDCl3, 298 K): d 1.4 (s, 9H), 1.5 (s, 9H), 6.3 (s, 2H), 6.7 (s,1H), 6.8 (m, 2H), 7.0 (d, 1H), 7.3 (d, 2H), 7.4 (d, 1H), 8.7 (s, 1H). nmax(KBr)/cm1: 3421 (OeH, NeH) 2951 (CeH) 1466 (CeH), 1212(CeO), 1607 (C]N) 651(CeH, methylene). ESI-MS m/z (%): 325.5 [MHLBAP1]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In ethanol at 20℃; Inert atmosphere; | General procedures for the preparationof catechol thioethers 1-7 General procedure: The target compounds were prepared according to reportedprocedure with some modifications [31]. The appropriatethiol (4.5 mmol in 10 cm3 ethanol) was added dropwise toa solution of 3,5-di-tert-butyl-o-benzoquinone in 20 cm3ethanol (3.0 mmol) over a period of 4-5 h and the mixturewas stirred under argon until decolouration of the reactionmedia at room temperature. The volume was concentratedunder a reduced pressure to yield a crude solid which wasrecrystallized in acetonitrile. Reaction of 3,5-di-tert-butylo-benzoquinone with thiosalicylic acid was performed inethanol under the same conditions. A dropwise addition ofthiosalicylic acid in ethanol to the reaction mixture resultedin the formation of a beige precipitate. Upon completion ofaddition of thiosalicylic acid solution the stirring wascontinued before decolouration of the reaction media. Thevolume was concentrated under reduced pressure to 5 cm3and resulting solid 4 was collected by filtration, washedwith cold EtOH, and air-dried. |
70% | In ethanol at 20℃; Inert atmosphere; | General procedure: Compounds 1-8 were synthesized using the modified known procedure.38 A solution of thiol (4.5 mmol) in ethanol (10 mL)was added dropwise to a solution of 3,5-di-tert-butyl-o-benzoquinone (0.66 g, 3.0 mmol) in ethanol (20 mL) over 4-5 h at room temperature under argon to the complete bleaching of the reaction mixture. The solvent was evaporated under reduced pressure. The formed precipitate was recrystallized from acetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In ethanol at 20℃; Inert atmosphere; | General procedures for the preparationof catechol thioethers 1-7 General procedure: The target compounds were prepared according to reportedprocedure with some modifications [31]. The appropriatethiol (4.5 mmol in 10 cm3 ethanol) was added dropwise toa solution of 3,5-di-tert-butyl-o-benzoquinone in 20 cm3ethanol (3.0 mmol) over a period of 4-5 h and the mixturewas stirred under argon until decolouration of the reactionmedia at room temperature. The volume was concentratedunder a reduced pressure to yield a crude solid which wasrecrystallized in acetonitrile. Reaction of 3,5-di-tert-butylo-benzoquinone with thiosalicylic acid was performed inethanol under the same conditions. A dropwise addition ofthiosalicylic acid in ethanol to the reaction mixture resultedin the formation of a beige precipitate. Upon completion ofaddition of thiosalicylic acid solution the stirring wascontinued before decolouration of the reaction media. Thevolume was concentrated under reduced pressure to 5 cm3and resulting solid 4 was collected by filtration, washedwith cold EtOH, and air-dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With air In n-heptane at 20℃; for 2h; | Synthesis of H2LDAP To a solution of 3,5-DTBQ(0.44 g, 2 mmol) in n-heptane(5mL) was added 1,3-diaminopropane (0.08 mL, 1 mmol), andthe reaction stirred for 2h at room temperature in the presenceof air. The yellow precipitate was formed. The pale yellowishmicrocrystals were grown from a 1:1 solvent mixture ofdichloromethane/n-heptane (Scheme 2).Yield: 0.220 g (45%). Anal. calcd. (found) for C31H50N2O2: C77.13 (77.01), H 10.44 (10.39), N 5.80 (5.76).νmax(KBr)/cm-1:3367 (O-H), 3291 (N-H), 2962, 2715, 2601 (C-H), 1593(C=C), 1486 (C=N), 1141 (C-N), 884-596 (=C-H bending). 1HNMR (400 MHz, deuterated DMSO, 298 K): δ 1.216 (s, 9H),2.514, 2.519, 2.523, 2.528, 2.532, 2.546 (s, 9H), 3.216(sextet), 3.349 (s), 4.475 (s, 2H), 6.507, 6.513 (d, 1H), 6.597,6.603 (d, 1H), 7.289 (s, 1H). 13C{H}NMR (100 MHz,deuterated DMSO): δ 30.34, 31.98, 34.22, 34.93, 38.97, 39.18,39.39, 39.59, 39.80, 40.01, 40.22, 111.70, 112.06, 136.88,137.34, 140.29, 142.07. m.p. 158-161 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | In ethanol at 20℃; Inert atmosphere; | 4.1.3. Synthesis of catechol thioethers 1-9 General procedure: The target compounds were prepared according to reported procedure [55] with some modifications. The appropriate thiol (3 mmol in10 ml ethanol) was added dropwise to a solution of 3,5-di-tert-butyl-obenzoquione (2.0 mmol, 0.44 g) in 15 ml ethanol over a period of 4-5 hand the mixture was stirred at room temperature under argon till decolouration of the reaction media. The volume was concentrated under a reduced pressure to yield a crude solid which was recrystallized from acetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | In ethanol; at 20℃;Inert atmosphere; | General procedure: The target compounds were prepared according to reported procedure [55] with some modifications. The appropriate thiol (3 mmol in10 ml ethanol) was added dropwise to a solution of 3,5-di-tert-butyl-obenzoquione (2.0 mmol, 0.44 g) in 15 ml ethanol over a period of 4-5 hand the mixture was stirred at room temperature under argon till decolouration of the reaction media. The volume was concentrated under a reduced pressure to yield a crude solid which was recrystallized from acetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With ammonium acetate In acetic acid at 118℃; for 24h; | Typical procedure for preparation of 2-(2-(4,5-diphenyl-1H-imidazol-3-ium-2-yl)phenoxy)acetate (7a) General procedure: A solution of benzil (0.21 g, 1 mmol), 2-(2-formylphenoxy)acetic acid (0.18 g, 1 mmol) and ammonium acetate (excessamount) in AcOH (5 mL) was heated at reflux for 24 h. After completion of the reaction, as indicated by TLC (ethylacetate/n-hexane, 3/1), the mixture was cooled to room temperatureand poured into cold H2Oto precipitate the crude product7a as cream powder (0.32 g, yield 86%); mp 160-163 °C. IR(KBr) cm-1: 3048, 2929, 2848, 1733, 1652, 1600, 1489, 1407.1H NMR (300.13 MHz, DMSO-d6) δ: 3.59-3.98 (1H, bm,NH), 4.01-4.06 (1H, m, NH), 4.89 (2H, s, CH2),7.10-8.21(14H, m, H-Ar). 13C NMR (100.62 MHz, DMSO-d6) δ: 66.6,114.4, 118.9, 122.3, 127.7, 128.2, 128.4, 129.0, 130.4, 133.2,143.4, 154.6, 172.0. Anal. calcd for C23H18N2O3:C, 74.58; H,4.90; N, 7.56; found C, 78.50; H, 4.91; N, 7.46 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile at 20℃; Inert atmosphere; | 4.2. General procedure for the synthesis of benzo[1,4]oxazines General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL,2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq),were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL),respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1,4]oxazine product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 20℃;Inert atmosphere; | General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL,2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq),were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL),respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1,4]oxazine product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 20℃;Inert atmosphere; | General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL,2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq),were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL),respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1,4]oxazine product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 20℃;Inert atmosphere; | General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL,2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq),were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL),respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1,4]oxazine product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 20℃;Inert atmosphere; | General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL,2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq),were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL),respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1,4]oxazine product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 20℃;Inert atmosphere; | General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL,2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq),were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL),respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1,4]oxazine product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 20℃;Inert atmosphere; | General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL,2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq),were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL),respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1,4]oxazine product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: acetonitrile / 20 °C / Inert atmosphere 2: iodine; triethylamine / 0 - 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile at 20℃; Inert atmosphere; | 4.2. General procedure for the synthesis of benzo[1,4]oxazines General procedure: To a stirred solution of ortho-benzoquinone (0.825 mmol, 1.0equiv) in acetonitrile (4.0 mL), was added dropwise a solution ofprimary amine (0.825 mmol, 1.0 equiv) in acetonitrile (4.25 mL)over 5 min under an argon atmosphere. The deep green colouredsolution was stirred at room temperature for 2e8 h. Aftercompletion of the reaction, as indicated by TLC, the reactionmixture was cooled to 0C. To this, triethylamine (0.34 mL,2.48 mmol, 3 equiv) and iodine granules (0.419 g, 1.65 mmol, 2 eq),were added. The resulting mixture was stirred vigorously for10e60 min under argon atmosphere. Upon completion, the reac-tion mixture was diluted with water and extracted with EtOAc(3 5 mL). The combined organic layer was washed with aqueoussaturated sodium thiosulfate (1 10 mL) and brine (2 10 mL),respectively, dried over Na2SO4, ltered, and concentrated in vacuo.The crude residue was puried by silica gel column chromatog-raphy eluting with pentane:EtOAc (95:5e80:20 v:v) to afford thedesired benzo[1,4]oxazine product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Reflux; | Quinone 1 (0.22 g, 1 mmol) and acetyl cysteine 6 (0.16 g, 1 mmol) were boiled in AcOH (1 mL) for 3-4 min until dissolution, and cooled to ~20 C. The precipitate was filtered off , washed with cold ether, and dried. The yield of crude product was 0.296 g (59%) being a solvate with an AcOH molecule. Colorless substance with m.p. 175-180 C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic anhydride; for 3h;Milling; | B. Quinone 1 (0.22 g, 1 mmol) and acetylcysteine 6 (0.17 g,1 mmol) were ground in an agate mortar. The mixture was transferred to a 25 mL flask, Ac2O (1 mL) was added, and this was triturated with a stick until dissolution and further quick thickening. The substance was kept for 3 h, EtOH (2 mL) and then H2O (5 mL) were added. The yield of crude product was 0.326 g (89%). M.p. 208-211 C (from AcOH). Found (%): , 62.23; , 7.61; S, 8.52. 19H27NO4S. Calculated (%): , 62.44; , 7.45; S, 8.77.IR, /cm-1: 3414 vs; 3170 br. (OH, NH); 1765 vs; 1655 vs ();1588 w; 1548 w (arom). 1H NMR (600 MHz, DMSO-d6), :1.36, 145 (both s, 18 , But); 1.83 (s, 3 , Me); 2.86 (dd, 1 ,2(ax), 2J = 12.1 Hz, 3J = 8.1 Hz); 3.25 (dd, 1 , 2(eq),2J = 12.1 Hz, 3J = 10.9 Hz); 4.55 (dd, 1 , (3), 3J = 8.1 Hz,3J = 10.9 Hz); 7.20 (s, 1 , (7)); 8.60 (d, 1 , NH, 3J = 8.1 Hz).13C NMR (150 MHz, DMSO-d6) : 22.17 ((3)); 29.08 ((6),(8)); 30.85 (C(6), C(8)); 35.12 (C(6)); 36.20 (C(4));36.41 (C(8)); 49.25 (C(3)); 118.15 (C(5a)); 121.55 (C(7));138.36 (C(6)); 142.26 (C(8)); 143.18 (C(9a)); 144.19 (C(9));168.65 (C(3)); 169.28 (C(2)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With trifluoroacetic acid; In acetonitrile; at 71.84℃; | General procedure: 0.22 g (1 mmol) of 3,5-di-(tert-butyl)-1,2-benzoquinone, 0.38 g (2mmol) of 2-amino-4-bromophenol 3h and 0.5 ml of trifluoroacetic acidwere dissolved in 20 mL of acetonitrile. The solution was stirred at refiluxduring 6-8 h. The product was purified by column chromatography overAl2O3 (toluene) to select the fraction with orange fluorescence with Rf ~0.88. The solvent was evaporated and the compound again was purifiedby column chromatography over SiO2 (toluene) to completely separatethe starting material. The product was obtained as the red crystals 215mg (56%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With trifluoroacetic acid In acetonitrile at 71.84℃; | 2.2.8. 9-bromo-2,4-di-(tert-butyl)benzo[5,6][1,4]oxazino[2,3-b]phenoxazine, 4h 0.22 g (1 mmol) of 3,5-di-(tert-butyl)-1,2-benzoquinone, 0.38 g (2mmol) of 2-amino-4-bromophenol 3h and 0.5 ml of trifluoroacetic acidwere dissolved in 20 mL of acetonitrile. The solution was stirred at refiluxduring 6-8 h. The product was purified by column chromatography overAl2O3 (toluene) to select the fraction with orange fluorescence with Rf ~0.88. The solvent was evaporated and the compound again was purifiedby column chromatography over SiO2 (toluene) to completely separatethe starting material. The product was obtained as the red crystals 215mg (56%). M.p. 249-251 C. IR (cm 1): 2960.5, 2867.4, 1560.2,1527.9, 1439.7, 1361.6, 1287.3, 1236.2, 1175.5, 991.8, 858.73, 812.9,646.5; 1H NMR (CDCl3) (ppm): 1.34 (9H, s, t-Bu), 1.46 (9H, s, t-Bu),6.49 (1H, s, 6-H), 6.51 (1H, s, 13-H), 6.92 (1H, d, J 8.7 Hz, 3-H),7.30-7.38 (3H, m, 1-H, 10-H, 11-H), 7.54 (1H, d, J 2.4 Hz, 8-H); m/z: [M] calcd. for C26H25BrN2O2, 477.1172; found, 477.1167. Anal.calcd. for C26H25BrN2O2: C, 65.41; H, 5.28; Br, 16.74; N, 5.87; found: C,65.62; H, 5.32; Br, 16.89; N, 5.47. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With trifluoroacetic acid In acetonitrile at 71.84℃; | 2.2.8. 9-bromo-2,4-di-(tert-butyl)benzo[5,6][1,4]oxazino[2,3-b]phenoxazine, 4h General procedure: 0.22 g (1 mmol) of 3,5-di-(tert-butyl)-1,2-benzoquinone, 0.38 g (2mmol) of 2-amino-4-bromophenol 3h and 0.5 ml of trifluoroacetic acidwere dissolved in 20 mL of acetonitrile. The solution was stirred at refiluxduring 6-8 h. The product was purified by column chromatography overAl2O3 (toluene) to select the fraction with orange fluorescence with Rf ~0.88. The solvent was evaporated and the compound again was purifiedby column chromatography over SiO2 (toluene) to completely separatethe starting material. The product was obtained as the red crystals 215mg (56%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With trifluoroacetic acid In acetonitrile at 71.84℃; | 2.2.8. 9-bromo-2,4-di-(tert-butyl)benzo[5,6][1,4]oxazino[2,3-b]phenoxazine, 4h General procedure: 0.22 g (1 mmol) of 3,5-di-(tert-butyl)-1,2-benzoquinone, 0.38 g (2mmol) of 2-amino-4-bromophenol 3h and 0.5 ml of trifluoroacetic acidwere dissolved in 20 mL of acetonitrile. The solution was stirred at refiluxduring 6-8 h. The product was purified by column chromatography overAl2O3 (toluene) to select the fraction with orange fluorescence with Rf ~0.88. The solvent was evaporated and the compound again was purifiedby column chromatography over SiO2 (toluene) to completely separatethe starting material. The product was obtained as the red crystals 215mg (56%). |
Tags: 3383-21-9 synthesis path| 3383-21-9 SDS| 3383-21-9 COA| 3383-21-9 purity| 3383-21-9 application| 3383-21-9 NMR| 3383-21-9 COA| 3383-21-9 structure
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P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
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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