- Synthetic method for antitumor drug intermediate 3,5-di-tert-butyl-4-hydroxybenzoic acid
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The invention discloses a synthetic method for the antitumor drug intermediate 3,5-di-tert-butyl-4-hydroxybenzoic acid. The synthetic method comprises the following steps: adding 2-amino-3,5-di-tert-butyl-4-hydroxy-6-bromo-benzyl alcohol and a sodium sulfate solution into a reaction vessel, controlling the speed of stirring, controlling a solution temperature, carrying out a reaction, adding anitromethane solution, raising the solution temperature and the stirring speed, and continuing the reaction; and adding a diethyl glutarate solution and niobium pentachloride powder, carrying out a reaction, carrying out washing with a sodium bromide solution a plurality of times, adding an oxalic acid solution to adjust a pH value, carrying out washing with a 1,2-diphenylethane solution a plurality of times, then carrying out recrystallization in a dibutylamine solution, and carrying out dehydration with a dehydrating agent so as to obtain the finished 3,5-di-tert-butyl-4-hydroxybenzoic acid.
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Paragraph 0015; 0020; 0024; 0025-0029
(2018/07/30)
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- 3. 5 - Di-tert-butyl -4 - hydroxy benzoic acid production method (by machine translation)
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The invention discloses a 3, 5 - di-tert-butyl - 4 - hydroxy benzoic acid production method, comprises sequentially the following steps: nitrogen gas under the protection of the added to the reaction kettle 2, 6 - di-tert-butyl phenol, aqueous solution of potassium hydroxide and toluene, which divides the water under the condition of a reflux reaction; then to carbon dioxide in the reactor until the pressure is 0.1 - 3.0 mpa, pressure-maintaining condition kohl uncle - Schmidt reaction, after the reaction, the corresponding after-treatment, to obtain 3, 5 - di-tert-butyl - 4 - hydroxy benzoic acid crude product. The invention short reaction time, the conversion is high, the traditional gas-solid process and the existing solvent process for synthesizing process advantage is obvious, suitable for further industrialization. (by machine translation)
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Paragraph 0048-0072
(2019/01/16)
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- Preparation method of propofol and structural analogues of propofol
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The invention relates to a preparation method of propofol and structural analogues of propofol. The preparation method comprises the steps as follows: preparing an intermediate from p-hydroxybenzoic acid and alkyl alcohol as raw materials under the action of a solid acid catalyst, and then preparing a target product by a decarboxylase reaction. The preparation method has the characteristics of being green in synthesis, realizing biotransformation, causing little pollution, producing few by-products and the like, and is suitable for industrial production; the purity of the prepared products such as propofol is 99.6% or higher, which meets various medicinal standards.
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Paragraph 0096
(2017/08/28)
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- Bismuth-based cyclic synthesis of 3,5-di-tert-butyl-4-hydroxybenzoic acid via the oxyarylcarboxy dianion, (O2CC6H2 tBu2O)2-
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3,5-Di-tert-butyl-4-hydroxybenzoic acid can be made under mild conditions in a cyclic process from carbon dioxide and 3,5-di-tert-butyl-4-phenol using bismuth-based C-H bond activation and CO2 insertion chemistry starting with the Bi3+ complex, Ar′BiCl2, of the NCN pincer ligand, Ar′ = 2,6-(Me2NCH2) 2C6H3. Complexes of the recently discovered oxyaryl dianion, (C6H2tBu2-3,5-O-4) 2-, and the oxyarylcarboxy dianion, [O2C(C 6H2tBu2-3,5-O-4)]2-, are intermediates in the process. Further studies of the oxyarylcarboxy dianion in Ar′Bi[O2C(C6H2tBu 2-3,5-O-4)-κ2O,O′], show that it undergoes decarboxylation upon reaction with I2 and it reacts with trimethylsilyl chloride to produce the trimethylsilyl ether of the trimethylsilyl ester of 3,5-di-tert-butyl-4-hydroxybenzoic acid and the Ar′BiCl2 starting material.
- Kindra, Douglas R.,Evans, William J.
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supporting information
p. 3052 - 3054
(2014/03/21)
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- Method for producing 3,5-DI-TERT-BUTYL-4-hydroxybenzoic acid
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The present invention provides a method for producing 3,5-di-tert-butyl-4-hydroxybenzoic acid comprising:(1) providing 2,6-di-tert-butylphenol which may contain up to 0.5 % by weight of 3,3',5,5'-tetra-tert-butyl-4,4'-dihydroxybiphenyl;(2) reacting a basic alkali metal compound with an excess amount of the 2,6-di-tert-butylphenol, which is: in excess of the basic alkali metal compound, to give the alkali metal 2,6-di-tert-butylphenolate; and(3) reacting the alkali metal 2,6-di-tert-butylphenolate obtained in step (2) with carbon dioxide to give 3,5-di-tert-butyl-4-hydroxybenzoic acid. According to the method of the present invention, 3,5-di-tert-butyl-4-hydroxybenzoic acid can be obtained with high and stable yield.
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Page/Page column 6
(2010/02/14)
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- PROCESS FOR PRODUCTION OF HYDROXYBENZOIC ACIDS
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The present invention provides A method for producing a hydroxybenzoic acid compound comprising, preparing an alkali metal salt of a phenol compound from the phenol compound, and reacting the alkali metal salt of the phenol compound with carbon dioxide, wherein the step of preparing the alkali metal salt of the phenol compound from the phenol compound comprises the steps of:a) reacting an alkali metal alkoxide with an excess amount of the phenol compound, which is in excess of the alkali metal alkoxide, to give the alkali metal salt of the phenol compound, andb) distilling away the generated alcohol from the reaction simultaneously with carrying out step a). The method of the present invention makes it possible to produce hydroxybenzoic acid compound in high yield without using aprotic polar organic solvent.
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Page/Page column 7
(2010/02/14)
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- PROCESS FOR PRODUCTION OF HYDROXYBENZOIC ACIDS
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The present invention provides a method for producing a hydroxybenzoic acid compound comprising, dehydrating a phenol compound and an alkaline metal compound to form the alkaline metal salt of the phenol compound and reacting the alkaline metal salt and carbon dioxide, wherein the dehydrating step is conducted by reacting the alkaline metal compound with an excess amount of the phenol compound at a temperature of 160°C or above. According to the method of the present invention, the hydroxybenzoic acid compound can be obtained by simple steps with low cost without using an expensive aprotic polar organic solvent. The provided method can produce highly pure hydroxybenzoic acid compound comprising little by-products in high yield.
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- Bi0-catalyzed oxidation of mandelic acid derivatives: Substrate selectivity
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A series of mandelic acid derivatives was oxidized with a bismuth-catalyzed oxidation system based on Bi0/DMSO/O2. Benzaldehyde and/or benzoic acid derivatives could be obtained chemoselectively depending on the catalytic system and the substitution on the aromatic ring. A strong substrate selectivity was observed, suggesting different oxidation mechanisms. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Favier, Isabel,Giulieri, Francoise,Dunach, Elisabet,Hebrault, Dominique,Desmurs, Jean-Roger
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p. 1984 - 1988
(2007/10/03)
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- Process for preparing hydroxybenzoic acids
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A process for preparing a hydroxybenzoic acid is herein disclosed which comprises reacting a phenol with an alkali metal compound by the use of an aprotic polar organic solvent as a reaction solvent to form an alkali metal salt of the phenol, and then reacting this alkali metal salt with carbon dioxide to obtain a hydroxybenzoic acid, said process comprising the step of carrying out the reaction under conditions that a molar ratio of the phenol to the total of the alkali metal compound and the aprotic polar organic solvent is larger than 1. Furthermore, the process may contain the steps of precipitating crystals from the reaction solution, separating the solid from the solution to obtain a wet alkali metal salt of the hydroxybenzoic acid, dissolving the wet alkali metal salt in water, and precipitating crystals from the solution by acidification to obtain the hydroxybenzoic acid.
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Page column 10,11
(2010/02/05)
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- Ozonation of 1,1,2,2-tetraphenylethene revisited: Evidence for electron- transfer oxygenations
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Ozonolyses of 1,1,2,2-tetraphenylethene (TPE, 1) have been described many times in the literature, but the reports are contradictory. This reaction is particularly important for understanding the mechanism of alkene ozonolysis, in view of possible stabilization of reactive intermediates by aryl groups. Thus, systematic investigations of ozonolysis in both aprotic solvents and in protic solvents are reported here. Attention is directed to the following details that have been underestimated in the past: i) the actual electronic structure of ground-state ozone (O3), ii) differentiation between strained and unstrained alkenes, iii) the significance of both the O3 concentration and the TPE concentration, iv) the influence of various solvents, including pyridine, v) the influence of the reaction temperature, vi) the role of electron-transfer catalysis (ETC) and, yii) the effect of structural modifications. Our results suggest that ozonolysis of TPE (1) does not include a 1,3-dipolar reaction step, but represents a particularly interesting example of electron-donor (TPE)/electron-acceptor (O3) redox chemistry. The present investigations include several crucial results. First, pure 3,3,6,6-tetraphenyltetroxane (3, m.p. 221°(dec.)) and pure tetraphenylethylene ozonide (4, m.p. 153°(dec.)) are prepared for the first time, although 3 and 4 have long been known. Second, the singlet diradical character of O3, lessened by means of hypervalent-electron interaction and predicted by different calculations, is evidenced via reaction with the spintrap galvinoxyl (2,6-bis(1-1-dimethylethyl)-4-{[3,5-bis(1,1- dimethylethyl)-4-oxocyclohexa-2,5-dien-1-ylidene]methyl}phenoxy; 8), and the zwitterionic reaction behavior of ground-state O3 is ruled out. Third, the electronacceptor ability of O3 is evidenced by reactions with suitable tetraaryl ethylenes: it is enhanced by addition of catalytic amounts of protons or Lewis acids. Fourth, the observed distribution of the O3 O-atoms to the two different olefinic C-atoms of the unsymmetric alkene 27b is in full agreement with an initial single-electron transfer (SET) step, followed by a radical mono-oxygenation to cause the crucial C,C cleavage. Final dioxygenation should lead to the generally known products (ozonides, tetroxanes, hydroperoxides). The regioselectivity is found to be inconsistent with the expected decay of an intermediate primary ozonide. Finally, the treatment of 1,2-bis(4-methoxyphenyl)acenaphthylene (36) with O3 (simultaneous transfer of three O-atoms) leads to the same experimental result as a stepwise transfer of one O-atom followed by a transfer of two O- atoms.
- Schank, Kurt,Beck, Horst,Buschlinger, Michael,Eder, Joerg,Heisel, Thomas,Pistorius, Susanne,Wagner, Christiane
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p. 801 - 826
(2007/10/03)
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- Antiviral use of a 2,6-di-t-butylphenol compound substituted in 4 position against herpes viruses and papillomaviruses
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A therapeutical use is provided for cornpounds selected from the group which consists of (a) phenols of formula (I): STR1 wherein R is a C1-12 alkyl group, a C2-12 alkenyl group, a C2-12 alkynyl group, a C1-12 alkoxy group, a formyl group, a C2-12 alkanoyl group, a C1-12 hydroxyalkyl group, a primary, secondary or tertiary amide group, an OCH3 group, CH2 OH or a COOH group or an A--COOH group where A is a C1-11 aliphatic hydrocarbon residue; and (b) the corresponding salts and esters thereof when R is COOH or A--COOH; for obtaining an antiviral drug for use in the human or veterinary therapeutical treatment of viral diseases.
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- Identification of Degradation Products of Terbutol in Environmental Water from Golf Courses
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Degradation products of terbutol (2,6-di-tert-butyl-4-methylphenyl N-methylcarbamate) in drainage and ground water from golf courses, on which terbutol had been applied as a herbicide, were identified by capillary GC/MS and reversed-phase HPLC. terbutol and 4-carboxy-, N-demethyl-, and 4-carboxy-N-demethylterbutol were detected in all water samples at concentrations of parts per billion levels.In addition, 4-(hydroxymethyl)- and 4-formylterbutol, 2,6-di-tert-butyl-4-methylphenol (BHT), and 4-(hydroxymethyl)-, 4-formyl-, and 4-carboxy-BHT were observed in some water samples at concentrations of parts per thousand levels.These results demonstrated that terbutol applied on golf courses was mainly degraded by N-demethylation, oxidation of the 4-methyl group, and hydrolysis of the carbamate ester linkage. Keywords:Terbutol; 2,6-di-tert-butyl-4-methylphenyl N-methylcarbamate; identification; degradation
- Suzuki, Toshinari,Yaguchi, Kumiko,Ohnishi, Kazuo,Suga, Tetsuya
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p. 1712 - 1717
(2007/10/02)
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- Reactivity in the Para Oxo Ketene Route of Ester Hydrolysis. The Effect of Internal Nucleophilicity and the Irrelevance of B Strain
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The hydrolysis of 2,4-dinitrophenyl (DNP) esters of substituted 4-hydroxybenzoic acids obeys the equation kobsd = (ka + kb->)/(1 + +>/Ka) and involves a para oxo ketene intermediate.The ka term fits a Broensted equation against the pK of the 4-hydroxybenzoate (log ka = 1.15pKa - 11.71) provided the 2,6-positions of the benzoate are free.The ka term for the 2,6-dimethyl-4-hydroxybenzoate ester is 1015-fold larger than that for the parent 4-hydroxybenzoate ester.An electronic effect due to different hydroxyl pKa's may be calculated from the above linear free energy relationship to contribute 1.6percent of the discrepancy.The other component of the discrepancy is ascribed to a preferred alignment of the ester in the 2,6-dimethyl case perpendicular to the plane of the aromatic ring. The fused ketene in the microscopic reverse reaction has a LUMO acceptor orbital perpendicular to the plane of the ring, in agreement with our conclusions.Force-field calculations of nonbonding interactions indicate no strain release in the elimination mechanism giving rise to ka.The dramatic (107-fold) enhancement of the apparent second-order rate constant for alkaline hydrolysis of the 2,6-dimethyl ester compared with that of the corresponding 2',4'-dinitrophenyl 4-methoxy-2,6-dimethylbenzoate is due mostly to the steric strain imposed in the tetrahedral transition state for the latter reaction.This strain is not sufficient, however, to cause the normal BAc2 mechanism in the alkaline hydrolysis of mesitoates to change to a "square planar" concerted process.
- Thea, Sergio,Cevasco, Giorgio,Guanti, Giuseppe,Kashefi-Naini, Nasrin,Willams, Andrew
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p. 1867 - 1872
(2007/10/02)
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- Peroxy Esters. 9. Base- and Radical-Induced Decomposition of 1-Alkyl-3,5-di-tert-butyl-4-oxo-2,5-cyclohexadienyl 3,5-Di-tert-butyl-4-hydroxyperbenzoates
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The title peroxy esters 1, when deprotonated with t-BuOK in DMF to the corresponding phenolate anions, decompose even at -78 deg C to give compounds 2-10.These compounds result undoubtedly from homolysis of the peroxy bond in 1, indicating that the generation of a carbanion at the α-position of the acyl group in peroxy esters (via resonance in the present case) induces ready homolysis of the peroxy bond.The oxidation of 1 with one-electron oxidizing agents gives rise to the corresponding phenoxy radicals, which also induce homolysis of the peroxy bond.
- Nishinaga, Akira,Nakamura, Koichi,Matsuura, Teruo
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p. 3700 - 3703
(2007/10/02)
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- Nickel salt-ester stabilizing compositions
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Compositions of nickel salts of 4-hydroxybenzoic acids and esters of aliphatic or aromatic carboxylic acids, which esters have boiling points of at least about 250° C. are useful for stabilizing polyolefins against degradation by heat and ultraviolet radiation and for rendering polyolefins dyeable.
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- Nickel stabilizers and dye enhancers for polyolefins
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Products of the reaction of about 30 to 90 parts by weight of a compound of formula (I) STR1 wherein R1 and R2 are each alkyl radicals having up to 8 carbon atoms at least one of which is branched on the alpha carbon, and R3 and R4 are each hydrogen or an alkyl radical having up to 18 carbon atoms, and about 70 to 10 parts by weight, respectively, of a secondary or tertiary phosphite are useful for stabilizing polyolefins against degradation by heat and ultraviolet radiation and for rendering polyolefins dyeable by chelatable dyes such as aromatic ortho hydroxy azo dyes.
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- Preparation of 3,5-dialkyl-4-hydroxybenzoic acid
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A process for preparing a sterically hindered 3,5-dialkyl-4-hydroxybenzoic acid which comprises reacting a sterically hindered 2,6-dialkylphenol with an excess of sodium hydride or lithium hydride in a dry dipolar aprotic solvent, carboxylating the resulting anhydrous phenolate with an excess of carbon dioxide at atmospheric pressure and at a temperature of about 70° C. to 80° C., then destroying the excess sodium hydride or lithium hydride by addition of an alcohol, followed by acidifying the reaction mixture to obtain a high yield of the sterically hindered 3,5-dialkyl-4-hydroxybenzoic acid.
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