* 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.
Stage #1: Inert atmosphere; Heating Stage #2: at 70 - 90℃; for 1.5 h; Inert atmosphere
(1) equipped with N2 air duct,Three rotor, and a dropping funnel was added to the reaction flask 2,6-di-t-butylphenol, and 20.6g of zinc carbonate mass ratio of 1.5 and a mixture of tributyl tin acetate 0.072g,Melting under nitrogen protection and heating to obtain a reactant; (2) When the reaction temperature reaches 70 ° C,To the reactant of the step (1), 8.24 g of the reactant methyl acrylate was added dropwise.After the completion of the dropwise addition, the reaction was continued for 0.5 hours.After heating to 90 ° C for 1 hour,Cooled to 80 ° C,Adjust the reaction solution to neutral with hydrochloric acid,crystallization,After suction filtration,Get the product;The final product yield was 99percent and the purity without recrystallization was as high as 99.5percent.
96 - 96.7 %Chromat.
Stage #1: at 40 - 50℃; Stage #2: at 110 - 140℃; for 1.85 - 3.43333 h;
A 1-liter round bottom Pyrex flask equipped with a magnetic stir bar, temperature probe, heating mantle, and total condenser for distillate removal was used. The flask was initially charged with 350.7 g of molten 2,6-di-tert-butylphenol ("2,6-DTBP", 1.70 mol) at 40 to 50° C., 2.42 g of potassium hydroxide (KOH) pellet, and 14.7 g of DMSO. The pressure was then reduced to 15 mm Hg and the temperature was increased from 40° C. to 115° C. over 70 minutes to remove the water by-product. The resulting white slurry was then cooled to 110° C. A water-cooled total reflux condenser and a 250-ml addition funnel containing 155.6 g of methyl acrylate were installed to the reactor. The methyl acrylate ("MA") was added dropwise over 30 minutes, during which the temperature of the reactor was allowed to rise from 110° C. to 129° C. The reactor was heated further to 135° C. in 6 minutes, then cooled to 110° C. and held at 110° C. for 170 minutes. The red clear solution was analyzed by Gas Chromatography ("GC") and found to contain 1.2 area percent 2,6-di-tert-butylphenol and 96.0 area percent 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester. The pressure was then reduced to 20 mm Hg, and the excess methyl acrylate was stripped at 110° C. The intermediate was analyzed by GC and found to contain 93.9 wt. percent 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester and 0.67 wt. percent 2,6-DTBP. A 21.5 g portion of the 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester intermediate was used for physical property measurements. EXAMPLE 2 This example demonstrates another two-step method for the production of 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, isooctyl ester, which is suitable for use as an antioxidant. Step 1: Michael Reaction. A 12-liter round bottom Pyrex flask equipped with an overhead agitator, temperature probe, heating mantle, and a reflux condenser in series of a total condenser for distillate removal were used. The flask was initially charged with 4126.4 g of molten 2,6-DTBP (20.0 mol) at 40 to 50° C., 28.1 g of KOH pellet (0.50 mol), and 85.9 g of DMSO (1.1 mol). The pressure was then reduced to 20 mm Hg and the temperature was increased from 40° C. to 126° C. over 76 minutes to remove the water by-product. The resulting white slurry was then cooled to 110° C. Cooling water was then put to the jacket of the reflux condenser and 995.2 g of methyl acrylate (11.56 mol) was then added dropwise from a 1000-ml funnel to the reactor over 37 minutes, during which time the reactor temperature was allowed to rise from 110° C. to 117° C. A stream of nitrogen was injected between the heating mantle and the reactor wall to remove the heat. The dropping funnel was immediately recharged with an additional 847.4 g of methyl acrylate (9.84 mol), which was added dropwise to the reactor over 39 minutes, while the reactor temperature was allowed to increase to 130° C. The reactor temperature was then brought to 140° C. over 10 minutes before cooling to 110° C. over 25 minutes. After a 110 minute hold at 110° C., the reaction mass was found to contain 1.58 area percent 2,6-DTBP and 96.7 area percent 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester. The reaction mass was held for 30 minutes longer at 110° C., before the excess methyl acrylate was stripped off at 110° C. and 20 mm Hg. The resulting 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester was analyzed by GC and found to contain 0.47 wt. percent 2,6-DTBP and 94.85 wt. percent 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester, and 1.75 area percent diesters.
98.5 %Chromat.
Stage #1: at 40 - 110℃; Stage #2: at 110 - 120℃; for 5.23333 h;
A 1-liter round bottom Pyrex flask equipped with a magnetic stir bar, thermal probe, heating mantle, water-cooled total reflux condenser, and 250-ml addition funnel were used. The flask was initially charged with 309.3 g of molten 2,6-DTBP (1.50 mol) at 40-50° C., 4.21 g of potassium tert-butoxide (t-BuOK), and 16.82 g of tetrahydrofuran (THF) to form a slurry. The slurry was heated to 110° C. and 142.0 g of methyl acrylate was added dropwise from the addition funnel over 98 minutes while the reactor was maintained at 110-120° C. After holding at 120° C. for 3.6 additional hours, the red clear reaction mass was found (by GC) to contain 0.46 area percent 2,6-DTBP and 98.5 area percent 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester. The pressure was then reduced to 20 mm Hg to strip off the THF and excess methyl acrylate. The methyl ester intermediate contained 96.3 wt. percent 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester, 0.11 wt. percent 2,6-DTBP, 0.04 wt percent methyl acrylate, and 0.38 wt. percent THF.
Reference：
[1] Patent: CN108358781, 2018, A, . Location in patent: Paragraph 0046-0049
[2] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1989, vol. 38, # 8.2, p. 1677 - 1682[3] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1989, # 8, p. 1829 - 1835
[4] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1989, vol. 38, # 8.2, p. 1677 - 1682[5] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1989, # 8, p. 1829 - 1835
[6] Russian Chemical Bulletin, 2007, vol. 56, # 10, p. 2038 - 2042
[7] Patent: US2005/192455, 2005, A1, . Location in patent: Page/Page column 14
[8] Patent: US2005/192455, 2005, A1, . Location in patent: Page/Page column 11-12
[9] Patent: US2005/192455, 2005, A1, . Location in patent: Page/Page column 14-15
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[ 3852-09-3 ]
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[ 128-39-2 ]
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[1] Journal of Chemical Research, Synopses, 1995, # 9, p. 366 - 367
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12
[ 50-00-0 ]
[ 108-80-5 ]
[ 128-39-2 ]
[ 27676-62-6 ]
Yield
Reaction Conditions
Operation in experiment
92.3%
With hexamethylenetetramine In methanol; water at 120 - 140℃; for 6 h; Autoclave; Inert atmosphere
To a 1L autoclave with mechanical stirring, thermometer socket, pressure gauge, nitrogen replacement port, 178g of 2,6-di-tert-butylphenol, 24.48g of paraformaldehyde, 41.28g of isocyanuric acid and 4.4g of urotropine were added. 4.4g, under vacuum, nitrogen replacement for more than 3 times, after the last nitrogen replacement, under the condition of negative pressure (-0.01Mpa), 1000mL aqueous solution of 70percent by volume of methanol is pumped into the reactor, and then Nitrogen gas was introduced into the apparatus to a pressure of 0.6 MPa, and the temperature was raised under a nitrogen atmosphere. After the temperature was raised to 120 ° C for 2 hours, the temperature was further raised to 140 ° C for 4 hours, and the reaction was completed. The circulating water of the reaction kettle was cooled to 58 ° C to obtain a crude product, and the crude product was directly filtered, and the solid matter was dissolved in a 70percent by volume aqueous solution of methanol at a concentration of 70 ° C, and recrystallized by cooling, and then anhydrous at 55 ° C. The methanol was washed twice or more and dried to obtain a white crystalline material, which was the target product hindered phenolic antioxidant 3114, and the yield was 92.3percent.
Reference：
[1] Patent: CN108707122, 2018, A, . Location in patent: Paragraph 0020; 0021; 0028; 0029
13
[ 128-39-2 ]
[ 7175-54-4 ]
[ 80-15-9 ]
[ 15773-11-2 ]
Reference：
[1] Journal of the American Chemical Society, 2014, vol. 136, # 28, p. 9925 - 9937
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[ 489-01-0 ]
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[1] Journal of Organic Chemistry, 1996, vol. 61, # 6, p. 2006 - 2012
21
[ 128-39-2 ]
[ 728-40-5 ]
Yield
Reaction Conditions
Operation in experiment
65%
With nitric acid; acetic acid In cyclohexane at 10 - 20℃; for 0.25 h;
2,6-di-t-butylphenol (8 g, 39 mmoles) is dissolved in 25 ml of cyclohexane at 10° C. A mixture (1/1) of nitric acid/acetic acid (5 ml) is added dropwise to the reaction medium maintained at this temperature.. Then agitation is carried out for 15 minutes at ambient temperature, then the precipitate formed is filtered, followed by rinsing with water and with pentane.. The 2,6-di-t-butyl-4-nitrophenol obtained (6.34 g, 65percent) is dried in an oven and will be used without other purification in the following stages.. Pale yellow powder.. Melting point: 167-168° C. NMR 1H (CDCl3, 100 MHz, δ): 1.48 (s, 18H, 2 TBu); 5.93 (s, 1H, OH); 8.13 (s, 2H, arom H.).
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[4] Patent: US6727239, 2004, B1, . Location in patent: Page column 19
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[6] Canadian Journal of Chemistry, 1984, vol. 62, p. 2803 - 2812
[7] Patent: US2868844, 1957, ,
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[11] Chemistry Letters, 1992, # 9, p. 1743 - 1746
[12] Patent: US5354782, 1994, A,
[13] Patent: EP1857444, 2007, A1, . Location in patent: Page/Page column 19
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[1] Canadian Journal of Chemistry, 1984, vol. 62, p. 2803 - 2812
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[1] Patent: CN107011149, 2017, A, . Location in patent: Paragraph 0064-0067
With (phthalocyaninato)iron(II); In methanol; at 20℃; for 5h;
A methanol solution (100 mL) of 2,6-di-t-butylphenol (309 mg, 1.5 mmol) was oxidized under the presence of phthalocyanine-Fe (II) (853 mg, 1.5 mmol) at a room temperature for 5 hours according to a method of ]. The resultant reaction mixture was stirred until the reaction was completed, and then evaporated. The resulting residue was dissolved in ethanol, filtered, and evaporated to yield a crystal, probucol diphenoquinone (340 mg, 100%). Electron impact mass spectra (EI-MS) were recorded on a double-focusing mass spectrometer (AX505W: JEOL). mp 223-225C 1H NMR (CDCl3) delta: 1.37 (36H, s), 7.71 (4H, s) EI-MS (m/z): 408 (M), 393 (M-CH3), 351 (M-C4H9)
98%
With copper ion-supported hydrophobically modified D301 resin; air; In 1,2-dichloro-ethane; at 80℃; for 3h;
100 g of 2,6-di-tert-butylphenol was dissolved in 800 g of dichloroethane, and 4 g of the above copper ion-supported hydrophobically modifiedD301 resin catalyst, 80 g of continuous air was introduced, stirred and reacted at 80C for 3 hours, and the filtrate was filtered to recover the above copper ionsSupported hydrophobic modified D301 resin catalyst.The filtrate was distilled to give a residue. The residue was washed with ethanol and dried to give 3,3 ', 5,5'-tetrakisTert-butyl-4,4'-biphenoquinone.The yield of 3,3 ', 5,5'-tetra-t-butyl-4,4'-biphenoquinone was calculated to be 98%, and the copper ion content in the product was3.0mug / g, the product purity is 99.9%.
90%
With manganese (II) acetate tetrahydrate; sodium hydroxide; In methanol; water; at 25℃; for 4h;Catalytic behavior;
2.5 Oxidative CC coupling of 2,6-di-tert-butylphenol (conversion of 2,6-di-tert-butylphenol to 3,3'-5,5'-tetra-tert-butyldiphenoquinone) Oxidative coupling of 2,6-di-tert-butylphenol (2,6-DTBP) was performed by taking 2,6-DTBP in methanol, sodium hydroxide in water was added to it such that the overall concentration is 10 mol%. To the above solution MII acetate (0.01 mmol) (MII = MnII, FeII, CoII, NiII, CuII) in methanol was added and the mixture was stirred at 25 C for 4-24 h. Product started forming as red precipitate after an hour of addition of MII acetate solution. On completion of the reaction the product was collected by filtration, washed by methanol and dried. The product was found to be pure by TLC and hence the dried product was analyzed by ESI-MS and 1H NMR spectroscopy. ESI-MS (positive ion mode): m/z = 409.30 [(DPQH)]+ (calc. 409.31); m/z = 431.29 [(DPQNa)]+ (calc. 431.29). 1H NMR (500 MHz, CDCl3): delta = 7.71(s, 4H), 1.36 (s, 36H) ppm.
72%
With potassium hydroxide; In water; tert-butyl alcohol; at 20℃; for 24h;
DPQ was prepared by adapting a procedure described in the literature.3 2,6-di-tert-butilfenol (8.288 g, 40 mmol), tert-butanol(100 mL), and a KOH solution (8 g in 12 mL of water) were added to a 250 mL Erlenmeyer flask, and the mixture was stirred open to air at room temperature. The initial yellow solution changed to orange and then to red during the first hour of the reaction, becoming eventually a brown-red suspension. After 24 hours, 30 mL of water were added to the mixture,filtered off, washed with water and dried to obtain 7.2086 g (88 %) of a red-brown powder. Further recrystallization with a toluene/ethanol mixture gave 5.8727 g (72 %)of long red-brown needles with a purple reflux
32%
With oxygen; potassium hydroxide; In water; tert-butyl alcohol; at 20℃; for 0.5h;
KOH (2.8 g, 50.0 mmol) was added to a mixture of t-butanol (50 mL) and H 2 O (1 mL) under an O 2 atmosphere. After stirring for 10 min, 2,6-di-tert-butylphenol (2.06 g, 10.0 mmol) was added portionwise. The resulting reaction solution is stirred at room temperature Mix and TLC monitor the reaction. The reaction mixture was poured into H 2 (100 mL) and stirred for 30 min. The resulting solid was used in small amounts of MeOHWashed and filtered to obtain 3,3',5,5'-tetra-tert-butyl-[1,1'-di(cyclohexadienyl)-2,2',5,5'-tetraene-4 , 4'-two Ketone (0.66 g, yield 32%).
With copper(l) chloride; In DMF (N,N-dimethyl-formamide); at 60℃; for 10h;
10.3 g of 2,6-di-t-butylphenol was dissolved in 100g of N,N-dimethylformamide, 0.5g of copper(I) chloride was added thereto and stirred at 60C. The solution was heated for about 10 hours under air bubbling. The precipitates were collected by filtration, washed well with water and methanol and dried to give 9.6g of brown crystal (decomposition point: 248C, MS m/z 408 (MW=408.6)). The infrared absorption spectrum (KBr) of the dimer is shown in Fig. 1.
With copper(II) nitrate trihydrate; Trimethylenediamine; sodium chloride; In methanol; at 29.84℃;
All kinetic runs were performed at 303K, in methanol solution, using pseudo-first-order conditions for the copper complex (1:255). The formation of 3,3?,5,5?-tetra-tert-butyl-4,4?-dibenzoquinone, at 418nm (epsilon=3.95×104L mol-1 cm-1) was followed spectrophotometrically. Stock solutions of Cu(NO3)2·3H2O, 1,3-propanediamine or 1,4-butanediamine, sodium chloride or sodium bromide were prepared separately at the same concentration (0.0225M); 2,6-di-tert-butylphenol was prepared at 0.0229M. Aliquots of each reactive were used in order to obtain a final concentration of 0.00003M for the corresponding catalyst and 0.0077M for the substrate. At least three runs were averaged for each experiment. In order to compare these results with those published earlier [10,12], we have been employed the same concentrations.
With nitric acid; acetic acid; In cyclohexane; at 10 - 20℃; for 0.25h;
2,6-di-t-butylphenol (8 g, 39 mmoles) is dissolved in 25 ml of cyclohexane at 10 C. A mixture (1/1) of nitric acid/acetic acid (5 ml) is added dropwise to the reaction medium maintained at this temperature.. Then agitation is carried out for 15 minutes at ambient temperature, then the precipitate formed is filtered, followed by rinsing with water and with pentane.. The 2,6-di-t-butyl-4-nitrophenol obtained (6.34 g, 65%) is dried in an oven and will be used without other purification in the following stages.. Pale yellow powder.. Melting point: 167-168 C. NMR 1H (CDCl3, 100 MHz, delta): 1.48 (s, 18H, 2 TBu); 5.93 (s, 1H, OH); 8.13 (s, 2H, arom H.).
With nitronium tetrafluoroborate; In sulfolane; dichloromethane;
Step a: 3,5-Di-t-butyl-4-hydroxy-nitrobenzene Dissolve 2,6-di-t-butylphenol (721 mg, 3.5 mmol) in methylene chloride (10 mL) and cool to -60 C. Add, by dropwise addition, a solution of nitronium tetrafluoroborate (25 mL of a 0.5M solution in sulfolane, 12.5 mmol) in methylene chloride (15 mL). Warm slowly to 10 C. and partition between methylene chloride (75 mL) and water (75 mL). Separate the aqueous phase and extract with methylene chloride (50 mL). Combine the organic phases, dry (MgSO4) and evaporate the solvent in vacuo. Purify and separate by flash silica gel chromatography to give the title compound.
With nitric acid; In 2,2,4-trimethylpentane; water; at 0 - 20℃; for 1.0h;
2,6-Di-tert-butylphenol (5.00 g) was dissolved in isooctane (20 mL), 70% nitric acid (1.54 mL) was added under ice-cooling, and the mixture was allowed to warm to room temperature and stirred for 1 hr. The precipitate was collected by filtration, washed with water, and recrystallized from methanol to give the title compound as crystals (3.00 g). IR nu (Nujol) cm-1; 3543, 1510. 1H-NMR (CDCl3) delta (ppm); 1.47 (18H, s), 5.91 (1H, s), 8.12 (2H, s).
With [Cu(2,4-dihydroxypyrimidine-5-carboxylic acid)(phenanthroline)(CH3OH)]NO3.H2O; dihydrogen peroxide; sodium dodecyl-sulfate; potassium hydroxide; In water; at 60℃; for 5h;
At room temperature, equipped with a condenser and a thermometer 10ml three-necked flask were added 2,6-di-t-butylphenol (206mg,1mmol), potassium hydroxide (56mg, 1mmol), sodium dodecyl sulfate (SDS, 29mg, 1mmol), followed by addition of 5mLWater, stirring, adding copper complex (0.02mmol) as a catalyst. It was heated to 50 , with a 10mul syringeThe H2O2 (30percent) and slowly added dropwise to the mixed solution, was added 10 l of 15 minutes each, a total of twice, 5h the reaction was stopped.Reaction products were separated by TLC on silica gel thin layer previously prepared. The results show that: the conversion rate of 2,6-di-tert-butyl-phenol100percent, double the product benzoquinone content of 79percent, diphenyl quinone content of 21percent.
(1) equipped with N2 air duct,Three rotor, and a dropping funnel was added to the reaction flask 2,6-di-t-butylphenol, and 20.6g of zinc carbonate mass ratio of 1.5 and a mixture of tributyl tin acetate 0.072g,Melting under nitrogen protection and heating to obtain a reactant; (2) When the reaction temperature reaches 70 C,To the reactant of the step (1), 8.24 g of the reactant methyl acrylate was added dropwise.After the completion of the dropwise addition, the reaction was continued for 0.5 hours.After heating to 90 C for 1 hour,Cooled to 80 C,Adjust the reaction solution to neutral with hydrochloric acid,crystallization,After suction filtration,Get the product;The final product yield was 99% and the purity without recrystallization was as high as 99.5%.
With dimethyl sulfoxide;potassium hydroxide; at 120℃; for 3.75h;Product distribution / selectivity;
Step 1: Preparation of 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester Into a 1-liter round bottom flask equipped with magnetic stirring bar and connected to a Dean-Stark trap and cooling condenser under N2 atmosphere, the following were charged: 206.3 g 2,6-DTBP (1.00 mol) 31.6 g toluene 1.33 g KOH pellets (23.7 mmol, 2.37 mol %) 4.71 g (-4 mL) DMSO promoter (60 mmol, 6.0 mol %) The reaction was heated to 140 C. to remove the water/toluene azeotrope. A white slurry was obtained and 7.2 g hazy toluene was collected in the trap. The Dean-Stark trap was removed and a cooling condenser was connected to the reactor. The heating was reset to 120 C. Vigorous condensation was observed and 99.1 g (1.15 mol) of methyl acrylate was added over a 45-minute period. After three hours of heating at 120 C., the 2,6-di-tert-butylphenol conversion was about 98.5% complete.
96 - 96.7%Chromat.
A 1-liter round bottom Pyrex flask equipped with a magnetic stir bar, temperature probe, heating mantle, and total condenser for distillate removal was used. The flask was initially charged with 350.7 g of molten 2,6-di-tert-butylphenol (?2,6-DTBP?, 1.70 mol) at 40 to 50 C., 2.42 g of potassium hydroxide (KOH) pellet, and 14.7 g of DMSO. The pressure was then reduced to 15 mm Hg and the temperature was increased from 40 C. to 115 C. over 70 minutes to remove the water by-product. The resulting white slurry was then cooled to 110 C. A water-cooled total reflux condenser and a 250-ml addition funnel containing 155.6 g of methyl acrylate were installed to the reactor. The methyl acrylate (?MA?) was added dropwise over 30 minutes, during which the temperature of the reactor was allowed to rise from 110 C. to 129 C. The reactor was heated further to 135 C. in 6 minutes, then cooled to 110 C. and held at 110 C. for 170 minutes. The red clear solution was analyzed by Gas Chromatography (?GC?) and found to contain 1.2 area % 2,6-di-tert-butylphenol and 96.0 area % 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester. The pressure was then reduced to 20 mm Hg, and the excess methyl acrylate was stripped at 110 C. The intermediate was analyzed by GC and found to contain 93.9 wt. % 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester and 0.67 wt. % 2,6-DTBP. A 21.5 g portion of the 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester intermediate was used for physical property measurements. EXAMPLE 2 This example demonstrates another two-step method for the production of 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, isooctyl ester, which is suitable for use as an antioxidant. Step 1: Michael Reaction. A 12-liter round bottom Pyrex flask equipped with an overhead agitator, temperature probe, heating mantle, and a reflux condenser in series of a total condenser for distillate removal were used. The flask was initially charged with 4126.4 g of molten 2,6-DTBP (20.0 mol) at 40 to 50 C., 28.1 g of KOH pellet (0.50 mol), and 85.9 g of DMSO (1.1 mol). The pressure was then reduced to 20 mm Hg and the temperature was increased from 40 C. to 126 C. over 76 minutes to remove the water by-product. The resulting white slurry was then cooled to 110 C. Cooling water was then put to the jacket of the reflux condenser and 995.2 g of methyl acrylate (11.56 mol) was then added dropwise from a 1000-ml funnel to the reactor over 37 minutes, during which time the reactor temperature was allowed to rise from 110 C. to 117 C. A stream of nitrogen was injected between the heating mantle and the reactor wall to remove the heat. The dropping funnel was immediately recharged with an additional 847.4 g of methyl acrylate (9.84 mol), which was added dropwise to the reactor over 39 minutes, while the reactor temperature was allowed to increase to 130 C. The reactor temperature was then brought to 140 C. over 10 minutes before cooling to 110 C. over 25 minutes. After a 110 minute hold at 110 C., the reaction mass was found to contain 1.58 area % 2,6-DTBP and 96.7 area % 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester. The reaction mass was held for 30 minutes longer at 110 C., before the excess methyl acrylate was stripped off at 110 C. and 20 mm Hg. The resulting 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester was analyzed by GC and found to contain 0.47 wt. % 2,6-DTBP and 94.85 wt. % 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester, and 1.75 area % diesters.
98.5%Chromat.
A 1-liter round bottom Pyrex flask equipped with a magnetic stir bar, thermal probe, heating mantle, water-cooled total reflux condenser, and 250-ml addition funnel were used. The flask was initially charged with 309.3 g of molten 2,6-DTBP (1.50 mol) at 40-50 C., 4.21 g of potassium tert-butoxide (t-BuOK), and 16.82 g of tetrahydrofuran (THF) to form a slurry. The slurry was heated to 110 C. and 142.0 g of methyl acrylate was added dropwise from the addition funnel over 98 minutes while the reactor was maintained at 110-120 C. After holding at 120 C. for 3.6 additional hours, the red clear reaction mass was found (by GC) to contain 0.46 area % 2,6-DTBP and 98.5 area % 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester. The pressure was then reduced to 20 mm Hg to strip off the THF and excess methyl acrylate. The methyl ester intermediate contained 96.3 wt. % 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid, methyl ester, 0.11 wt. % 2,6-DTBP, 0.04 wt % methyl acrylate, and 0.38 wt. % THF.
N-(3,5-di-t-butyl-4-hydroxyphenyl)-5-[4-{imino(2-thienyl)-methylamino}phenyl]-2-furan carboxamide hydroiodide[ No CAS ]
[ 728-40-5 ]
Yield
Reaction Conditions
Operation in experiment
With nitric acid; acetic acid; In cyclohexane;
42.1 2,6-di-t-butyl-4-nitrophenol 2,6-di-t-butylphenol (8 g, 39 mmoles) is dissolved in 25 ml of cyclohexane at 10 C. A (1/1) mixture of nitric acid/acetic acid (5 ml) is added dropwise to the reaction medium maintained at this temperature. Agitation is then carried out for 15 minutes at ambient temperature. Then the precipitate formed is filtered off, rinsed with water and pentane. The 2,6-di-t-butyl-4-nitrophenol obtained (6.34 g, 65%) is dried in an oven and will be used without further purification in the following stages. Pale yellow powder. Melting point: 167-168 C. NMR 1H (CDCl3, 100 MHz, delta): 1.48 (s, 18H, 2tBu), 5.93 (s, 1H, OH), 8.13 (s, 2H, arom. H).
Example 3: Continuous Processing of Hindered Phenolic Esters (mixture of n-butyl and methyl acrylate) with a Continuous Phenoxide FormationThe same procedure of Example 1 is used except that in the four-reactor sys- tern of part two, n-butyl acrylate is fed into the first reactor at a rate of 1.52 kg/hr and at simultaneously, methyl acrylate is fed into the same reactor at a rate of 0.08 kg/hr.The use of a mixture of n-butyl and methyl acrylate in the process can preclude crystallation of the hindered ester-substituted phenol
With N,N?-(di-2,6-diisopropylphenyl)naphthalene-1,4,5,8,-tetracarboxylic acid bisimide; oxygen; potassium hydroxide; In methanol; at 90℃; for 24h;
To a three-necked flask, a MeOH solution of NDI 1 (for entry 2, 2 is absent), starting material 2 and KOH (for entry 3, KOH is absent) was added and then reacted at 20 °C (entry 5), 40 °C (entry 1) or 90 °C (entry 6) for 24 h or 200 h (the reaction progress is monitored by thin layer chromatography). After being cooled to room temperature, the cooled mixture was poured into 1 mol L?1 aqueous HCl (100 mL) and extracted with DCM (50 mL) twice. The obtained organic solution was washed with a saturated solution of NaHCO3 (50 mL) and water for two times, and further dried by anhydrous Na2SO4. Filtration and removal the organic solvents afford a brown solid, which was purified by column chromatography (SiO2, DCM:PE=1:1) affording compound 3 as a yellow solid (815 mg, 80 percent) and Compound 4 is a light yellow solid (70 mg, 5 percent) for entry 1, but 3 of 60 mg (ca. 5percent) and 4 of 817 mg (85 percent) for entry 6. For other trials (entry 2?5), almost no oxidative products was obtained.
80%; 5%
With N,N?-(di-2,6-diisopropylphenyl)naphthalene-1,4,5,8,-tetracarboxylic acid bisimide; oxygen; potassium hydroxide; In methanol; at 40℃; for 24h;
To a three-necked flask, a MeOH solution of NDI 1 (for entry 2, 2 is absent), starting material 2 and KOH (for entry 3, KOH is absent) was added and then reacted at 20 °C (entry 5), 40 °C (entry 1) or 90 °C (entry 6) for 24 h or 200 h (the reaction progress is monitored by thin layer chromatography). After being cooled to room temperature, the cooled mixture was poured into 1 mol L?1 aqueous HCl (100 mL) and extracted with DCM (50 mL) twice. The obtained organic solution was washed with a saturated solution of NaHCO3 (50 mL) and water for two times, and further dried by anhydrous Na2SO4. Filtration and removal the organic solvents afford a brown solid, which was purified by column chromatography (SiO2, DCM:PE=1:1) affording compound 3 as a yellow solid (815 mg, 80 percent) and Compound 4 is a light yellow solid (70 mg, 5 percent) for entry 1, but 3 of 60 mg (ca. 5percent) and 4 of 817 mg (85 percent) for entry 6. For other trials (entry 2?5), almost no oxidative products was obtained.
1,3-di-tert-butyl-2-(4-(tert-butyl)phenoxy)benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
20%
With di-tert-butyl{2?-isopropoxy-[1,1?-binaphthalen]-2-yl}phosphane; potassium phosphate; bis(dibenzylideneacetone)-palladium(0); In toluene; at 110℃; for 18h;Inert atmosphere;
General procedure: An oven-dried Schlenk tube was evacuated and backfilled with nitrogen. The Schlenk tube was charged with Pd(bda)2 (11.5 mg,0.02 mmol), L1 (13.7 mg, 0.03 mmol), K3PO4 (424.5 mg, 2 mmol), and toluene (1.0 mL). After stirring for 15 min, the solution of arylhalide (1.0 mmol) and phenol (1.2 mmol) in toluene (1.5 mL) was added. The septum was replaced with an inside reflux condenser, and then the reaction mixture was stirred for 18 h at 110 C. Then,the reaction mixture was cooled to room temperature and quenched with water (5 mL). After separating the organic phase, the aqueous phase was extracted with ethyl acetate (3 mL3), and the combined organic phase was dried over anhydrous Na2SO4. The solvent was concentrated under reduced pressure, and then the crude material was purified by column chromatography on silica gel
1,3-diallyl-5-(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanurate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N,N,N,N,N,N-hexamethylphosphoric triamide; In N,N-dimethyl-formamide; at 120℃; for 8h;
To a solution of 2,6-di-tert-butylphenol (2.06 g, 0.01 mol) in DMF is added paraformaldehyde (0.45 g, 0.OlSmol), <strong>[6294-79-7]diallyl isocyanurate</strong>(3.14 g, 0.015 mol) and HMTA (0.18 g, 0.00 1 mol). The resulting solution is stined at 120C for 8 hours. The reaction mixture is then quenched by addition of water and extracted with ethyl acetate. The combined organic layers are washed with brine, dried over sodium sulfate (Na2SO4), and concentrated under reduced pressure. The crude material is purified by flash column chromatography to obtain the desired product. 1H NMR (400 MHz, CDC13) oe 7.36 (s, 2H), 5.86 (m, 2H), 5.30 (m, 2H), 5.23 (m, 2H), 4.97 (s, 2H), 4.47 (d, 4H), 1.43 (s, 18H).
A mixture of 292 g (1 mol) of 3,5-di-tert-butyl-4-hydroxyphenylpropionic acid was addedMethyl esterWith 8.8 g of catalyst p-toluenesulfonic acid was added to the reactor,Heating up to 90 C reaction.HPLC monitoring reaction,When the raw material content is less than 20%When the intermediate content reaches 80%, the reaction is terminated.Step-dealkylation The high performance liquid chromatogram is shown in Fig.1Among them, impurity 1: tr = 3.208, content of 4.14%;Impurity 3: tr = 3.493, content 1.60%;Intermediate: tr = 5.385, content 80.08%;Raw materials: tr = 12.470, content of 10.96%;Impurity 2: tr = 16.067, content 2.35%.
3,5-di-tert-butyl-1′-methyl-1′,4′-dihydro-2′H-spiro[cyclohexane-1,3′-quinoline]-2,5-dien-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
45%
General procedure: Taking compound A1 (2,6-di-tert-butylphenol) 0.13 mmol,Compound B1 (2-pyrrolidinylbenzaldehyde) 0.1 mmolAnd piperidine 0.2 mmol in the reaction flask,Add 1 mL of toluene,Stir the reaction at 120 C for 12 h,After cooling to room temperature;Then added to the reaction system1 mL of hexafluoroisopropanol HFIP,Stir at 25 C for 10 min,After the reaction is over,The reaction product is subjected to rotary distillation to concentrate.Separate and purify on a silica gel column.Starting material: <strong>[7755-70-6]2-methylaminobenzaldehyde</strong>,2,6-di-tert-butylphenolReaction conditions: 25 C / HFIP, 40 min
With hydrogenchloride; 15-crown-5; 3,4,7,8-Tetramethyl-o-phenanthrolin; cadmium(II) iodide; ytterbium(III) triflate; In tetrachloromethane; water; at 50℃; for 10h;Catalytic behavior;
Add 100 mmol of the compound of the formula (I) and 320 mmol of the compound (II) to a suitable amount of a mixture of carbon tetrachloride and 15-crown-5 in a volume ratio of 5:1 at room temperature. Then adding a ternary composite catalyst (a mixture of Yb(OTf)3,3,4,7,8-tetramethyl-1,10-phenanthroline and CdI2, The mass ratio of the three is 1:0.2:0.05, the mass of the compound of the formula (I) and the ternary composite catalyst is 1:0.03), and the aqueous solution of dilute hydrochloric acid having a concentration of 3% by mass (the compound of the formula (I) and the rare The mass ratio of the aqueous hydrochloric acid solution is 1:0.5); Then, the temperature was raised to 50 C with stirring, and the reaction was carried out at this temperature for 10 hours. After the completion of the reaction, the mixture was filtered while hot, and the filtrate was washed thoroughly with deionized water 2-3 times. The organic phase was separated, concentrated under reduced pressure, and the residue was recrystallized from petroleum ether to give the desired product antioxidant 330. The yield was 99.5%.
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