- Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof
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Methods of synthesizing compounds comprising fluorinated aryl groups are disclosed, wherein said methods utilize hydrogen bond directed photocatalytic hydrodefluorination.
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- Continuous synthesis method for substituted benzoic acid organic matter
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The invention provides a continuous synthesis method for a substituted benzoic acid organic matter. The continuous synthesis method comprises the following steps: in the presence of a catalyst and anorganic solvent, continuously putting an organic matter of a formula (I) shown in the specification, and oxygen into a continuous reaction device, carrying out a continuous oxidation reaction so as toobtain the substituted benzoic acid organic matter, and continuously discharging the substituted benzoic acid organic matter, wherein the substituted benzoic acid organic matter is of a structure ofa formula (II) shown in the specification. Oxygen is a green reagent and is cheap and easy to obtain, a great amount of wastes are not generated after reactions are completed, and the system is easy to treat. Due to continuous reaction operation, the risk that the solvent has flash evaporation explosion because of high-concentration oxygen in in-batch reactions can be reduced. Under same oxidationconditions, due to a continuous preparation process, escape of oxygen can be reduced, the utilization rate of oxygen can be greatly increased, operation can be also simplified, the security of reactions can be improved, and the yield of the substituted benzoic acid organic matter can be increased.
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Paragraph 0040-0060; 0138
(2019/10/01)
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- Pharmaceutical intermediate 2,4-difluorobenzoic acid synthesis method
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The invention discloses a pharmaceutical intermediate 2,4-difluorobenzoic acid synthesis method, which mainly comprises: adding 3-4 mol of a 1,3-dichloro-2-propanol solution, 2 mol of a 2,4-difluoro-6-bromo-isopropylbenzene solution and 600-800 ml of an aqueous solution to a reaction container, controlling the stirring speed at 110-130 rpm, heating the solution to a temperature of 40-50 DEG C, adding 5-6 mol of a boron trifluoride-butyl ether solution, maintaining for 90-110 min, carrying out pressure reducing concentration after completing the reaction, adding 300 ml of a 1-pentanol solution,filtering, adjusting the pH value of the filtrate to 4-5, crystallizing, filtering, re-crystallizing in a 4-methyl-2-pentanone solution, and dewatering with a dewatering agent to obtain the finishedproduct 2,4-difluorobenzoic acid.
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Paragraph 0011; 0013; 0014; 0015
(2018/11/03)
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- Synthetic method of medical intermediate 2, 4-difluorobenzoic acid
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The invention discloses a synthetic method of medical intermediate 2, 4-difluorobenzoic acid. The synthetic method specifically includes following steps: adopting a sol-gel method to prepare nano silicon oxide loaded Pd as a catalyst; adding cetyl trimethyl ammonium chloride to perform in-situ modification on the surface of the catalyst in the process of preparation; adding ammonium chloride and the prepared catalyst into the raw material, namely 2, 4-dinitrotoluene, for reaction, collecting filtrate, and adding tetrabutylammonium bromide, manganese dioxide and hydrogen peroxide for reaction to obtain white solid; allowing N, N-dimethyl formamide, sodium fluoride, white solid and tetrabutylammonium bromide for reaction to obtain 2, 4-difluorobenzoic acid. The synthetic method is simple tooperate and high in target product yield.
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Paragraph 0019-0024; 0025-0030; 0031-0036; 0037-0048
(2018/05/16)
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- Preparing method of 2,4-difluorobenzoic acid
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The invention discloses a preparing method of 2,4-difluorobenzoic acid. According to the method, 2,4-dinitritoluene serves as a raw material, and a drug intermediate 2,4-difluorobenzoic acid is prepared through oxidization and fluorination, wherein potassium permanganate serves as an oxidizing agent, and potassium fluoride serves as a fluorinating agent. The synthesis method of the 2,4-difluorobenzoic acid is simple in technology, environmentally friendly, high in yield, and low in cost. According to the method, the total yield is 66%, and is obviously higher than that of other methods in theprior art.
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Paragraph 0013
(2018/03/24)
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- New method for non-metal catalytic oxidation synthesis of substituted benzoic acid compound
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The invention discloses a method for synthesis of a substituted benzoic acid compound, a Wittig reagent and hydrogen peroxide as raw materials are reacted by heating in an organic solvent at reaction temperature of room temperature or 50 DEG C, the reaction formula is as shown in the specification, in the formula, Ar is an aromatic ring substituent, X is an unsaturated ester substituent or an aromatic ring substituent. The method has the following beneficial effects: (1) the method has the advantages of simple operation, wide substrate application range, high yield, friendliness to the environment; (2) the Wittig reagent is simple in preparation, the raw materials are cheap, the Wittig reagent which is not participated in the reaction can also be recycled by recrystallization; (3) the reaction conditions of the Wittig reagent and the hydrogen peroxide are mild, and the post treatment is simple, the method is green and environmentally-friendly and is suitable for industrial enlargement; and (4) by-product triphenylphosphine oxide is also recyclable, is an important chemical raw material and can be applied as organic synthesis intermediates, pharmaceutical intermediates, catalysts and extractants.
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Paragraph 0055; 0056; 0057; 0058
(2018/01/11)
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- Palladium-Catalyzed Ligand-Controlled Selective Synthesis of Aldehydes and Acids from Aryl Halides and Formic Acid
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Selective synthesis is in the core of modern organic chemistry. In this communication, a novel ligand-dependent palladium-catalyzed carbonylation procedure for the divergent synthesis of aldehydes and carboxylic acids from easily available aryl halides was established. Under the same reaction conditions, the reaction pathway could be controlled by the ligands applied to give formylated and carboxylated products selectively. Sterically hindered monodentate ligands facilitated the reductive carbonylation and provided aldehydes, whereas bidentate ligands preferred the carboxylation reaction and produced carboxylic acids. A wide range of functional groups were tolerated, and the products were, in general, obtained in moderate to excellent yields.
- Wu, Fu-Peng,Peng, Jin-Bao,Meng, Ling-Shen,Qi, Xinxin,Wu, Xiao-Feng
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p. 3121 - 3124
(2017/08/29)
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- Room Temperature Carbonylation of (Hetero) Aryl Pentafluorobenzenesulfonates and Triflates using Palladium-Cobalt Bimetallic Catalyst: Dual Role of Cobalt Carbonyl
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An efficient method for the carbonylation of (hetero) aryl pentafluorobenzenesulfonates and triflates under exceptionally mild conditions using palladium/dicobalt octacarbonyl [Pd/Co2(CO)8] has been developed. Besides acting as carbon monoxide (CO) source, Co2(CO)8enhances the reaction rate by accelerating the CO insertion through an in situ generated bimetallic palladium cobalt tetracarbonyl [Pd-Co(CO)4] complex. Under the optimized reaction condition, carbonylation of a wide range of activated and deactivated, as well as sterically hindered and heteroaromatic, substrates proceeded efficiently at room temperature. The high chemoselectivity and improved synthesis of biologically relevant Isoguvacine and Lazabemide intermediates highlights its scope as a valuable synthetic method. The generality of this protocol was further extended to other electrophiles (bromides, chlorides and tosylates). (Figure presented.).
- Joseph, Jayan T.,Sajith, Ayyiliath M.,Ningegowda, Revanna C.,Shashikanth, Sheena
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supporting information
p. 419 - 425
(2017/02/10)
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- An outstanding catalyst for the oxygen-mediated oxidation of arylcarbinols, arylmethylene and arylacetylene compounds
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A convenient and sustainable protocol for the aerobic oxidation of benzyl alcohols to carbonyl compounds, based on the use of 1,2,4-triazole-type ligands and nickel(ii) bromide, is described. This combination leads to the formation of an exceedingly active, enzyme-like system that allows for other oxidative processes, such as benzylic C-H oxidation and oxygen-mediated cleavage of C-C triple bond, a pioneering procedure for transformation of alkynes into carboxylic acids.
- Urgoitia,Sanmartin,Herrero,Domínguez
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supporting information
p. 4799 - 4802
(2015/03/18)
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- An efficient one pot method for synthesis of carboxylic acids from nitriles using recyclable ionic liquid [bmim]HSO4 Dedicated to my mentor Professor (Mrs.) Krishna Misra on her 76th birthday
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Environmentally benign ionic liquid [bmim]HSO4 was found suitable for conversion of nitriles into carboxylic acids under mild conditions with excellent purity.
- Kumar, Satyanand,Dixit, Sandeep Kumar,Awasthi, Satish Kumar
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supporting information
p. 3802 - 3804
(2014/07/07)
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- Method for estimating SN1 rate constants: Solvolytic reactivity of benzoates
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Nucleofugalities of pentafluorobenzoate (PFB) and 2,4,6-trifluorobenzoate (TFB) leaving groups have been derived from the solvolysis rate constants of X,Y-substituted benzhydryl PFBs and TFBs measured in a series of aqueous solvents, by applying the LFER equation: log k = sf(Ef + Nf). The heterolysis rate constants of dianisylmethyl PFB and TFB, and those determined for 10 more dianisylmethyl benzoates in aqueous ethanol, constitute a set of reference benzoates whose experimental ΔG ? have been correlated with the ΔH? (calculated by PCM quantum-chemical method) of the model epoxy ring formation. Because of the excellent correlation (r = 0.997), the method for calculating the nucleofugalities of substituted benzoate LGs have been established, ultimately providing a method for determination of the SN1 reactivity for any benzoate in a given solvent. Using the ΔG? vs ΔH? correlation, and taking sf based on similarity, the nucleofugality parameters for about 70 benzoates have been determined in 90%, 80%, and 70% aqueous ethanol. The calculated intrinsic barriers for substituted benzoate leaving groups show that substrates producing more stabilized LGs proceed over lower intrinsic barriers. Substituents on the phenyl ring affect the solvolysis rate of benzhydryl benzoates by both field and inductive effects.
- Matic, Mirela,Denegri, Bernard,Kronja, Olga
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supporting information
p. 8986 - 8998,13
(2012/12/12)
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- Enzymatic Baeyer-Villiger oxidation of benzaldehydes
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The selectivity of the chemical Baeyer-Villiger oxidation of benzaldehydes depends on steric and electronic factors, the type of oxidizing agent and the reaction conditions. Here we report on the enzymatic Baeyer-Villiger oxidation of fluorobenzaldehydes
- Moonen, Marielle J. H.,Westphal, Adrie H.,Rietjens, Ivonne M. C. M.,Van Berkel, Willem J. H.
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p. 1027 - 1034
(2007/10/03)
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- Promoting or preventing haloaryllithium isomerizations: Differential basicities and solvent effects as the crucial variables
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Deprotonation-triggered heavy halogen migrations should become a favorite tool in arene synthesis if their occurrence and outcome could be made predictable. Particularly attractive, though extremely rare, are stop-and-go situations where a first intermediate, generated by metalation, can be trapped at -100 °C, whereas at -75 °C halogen migration gives rise to an isomer. As shown now, one can conveniently produce the initial aryllithium species by halogen/metal interconversion in toluene at -100 °C, under conditions that preclude, halogen migration, and unleash the isomerization process by adding tetrahydrofuran at -75 °C.
- Heiss, Christophe,Rausis, Thierry,Schlosser, Manfred
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p. 617 - 621
(2007/10/03)
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- Carboxylation and esterification of functionalized arylcopper reagents
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Functionalized arylcopper reagents have been produced in good yields at 25 °C from activated copper and the corresponding functionalized aryl iodides without the need of traditional organolithium or Grignard precursors. These organocopper compounds will undergo carboxylation with CO2 to form the corresponding copper benzoates. In turn, these salts can be acidified to produce the functionalized aryl acids or treated with appropriate alkyl halides in the presence of a dipolar aprotic solvent to generate the corresponding aryl esters. This methodology permits the formation of functionalized organic acids and esters that could not be generated by the carboxylation of organomagnesium compounds.
- Ebert, Greg W.,Juda, Wayne L.,Kosakowski, Robert H.,Ma, Bing,Dong, Liming,Cummings, Keith E.,Phelps, Mwita V. B.,Mostafa, Adel E.,Luo, Jianyuan
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p. 4314 - 4317
(2007/10/03)
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- Nitroarene catalyzed oxidation with sodium percarbonate or sodium perborate as the terminal oxidant
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A new catalytic oxidation method for the preparation of aromatic carboxylic acids from methyl aryl ketones is reported. The method is an alternative to the haloform reaction; it is benign and affords the desired product without production of any harmful side products. The catalytic cycle is based on the use of an electron-deficient nitroarene as catalyst with either of the two cheap and green oxidants sodium percarbonate or sodium perborate. The method gives a good yield (87%) and shows excellent selectivity when the model substrate (acetophenone) is oxidized. A series of benzoic acids of industrial interest were prepared by means of this method.
- Bj?rsvik, Hans-René,Merinero, José Angel Vedia,Liguori, Lucia
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p. 8615 - 8620
(2007/10/03)
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- Exploring Structural Opportunities: The Regioflexible Substitution of 1,3-Difluorobenzene
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To demonstrate the superiority of modern organometallic methods, the inexpensive starting material 1,3-difluorobenzene has been selectively converted into the three benzoic acids and all seven bromobenzoic acids containing the two fluorine atoms in homovicinal positions. The 2,6-difluorobenzoic acid (1) was prepared in a one-pot reaction consisting of direct metallation and carboxylation. The key step on the route to the bromobenzoic acid 4 was a deprotonation-triggered bromine migration from the 2- to the 4-position. All other products were attained through (2,6-difluorophenyl)triethylsilane (11). Consecutive deprotonation of the sites adjacent to the fluorine atoms, followed by appropriate electrophilic substitution, provided not only the acid 7 but also the dibromo and iodobromo derivatives 13 and 23. These in turn gave the isomers 14 and 24 upon base-mediated migration of the heaviest halogen, which made the acids 8 and 10 directly accessible. The regiocontrolled monodebromination of intermediate 14 afforded (4-bromo-2,6-difluoro)triethylsilane (15), which opened the route to the acids 3 and 5 (by carboxylation and protodesilylation) and to acid 9 (by carboxylation and bromodesilylation). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Schlosser, Manfred,Heiss, Christophe
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p. 4618 - 4624
(2007/10/03)
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- Phosphonic acid derivatives having carboxypeptidase b inhibitory activity
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A compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof: wherein R1represents hydrogen atom, an alkyl group, a substituted alkyl group and the like; R2and R3represent hydrogen atom, an alkyl group, a substituted alkyl group, an alkoxyl group and the like; X represents —CH2—, —O—, or —NH—; A represents the following group (II): [in which R7and R8represent hydrogen atom, an alkyl group, an acyl group, an alkoxycarbonyl group and the like; R9and R10represents hydrogen atom, a halogen atom, hydroxyl group, phenyl group, an alkyl group and the like] and the like; and E represents hydrogen atom and the like, which has inhibitory activity against carboxypeptidase B and is useful for therapeutic and/or preventive treatment of a thrombotic disease.
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- The basicity gradient-driven migration of iodine: Conferring regioflexibility on the substitution of fluoroarenes
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Six different fluoroarenes were submitted to the same transformations. Direct deprotonation with alkyllithium or lithium dialkylamide as reagents and subsequent carboxylation afforded the acids 1, 6, 11, 16, 18, and 23. If the aryllithium intermediate was trapped with iodine rather than with dry ice, an iodofluoroarene (2, 7, 12, 17, 19, and 24) was formed. This, upon treatment with lithium diisopropylamide, underwent deprotonation and iodine migration. The resulting new aryllithium species was intercepted either by carboxylation, to give the acids 3, 8, 13, 20, and 25, or by neutralization, to produce the iodofluoroarenes 4, 9, 14, 21, and 26. The latter family of compounds was converted into another set of acids 5, 10, 15, 22, and 27 by subsequent treatment with butyllithium or isopropylmagnesium chloride and carbon dioxide. ( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).
- Rausis, Thierry,Schlosser, Manfred
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p. 3351 - 3358
(2007/10/03)
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- Fragmentation of radical anions of polyfluorinated benzoates
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A comprehensive study of the symmetry forbidden fragmentation of short-lived radical anions (RAs) has been undertaken for the complete set of polyfluorinated benzoates (C6FnH5-nCO22, n = 1-5). The decay rate constants (kc) of RAs have been determined in aqueous alkaline solution (pH 13.4) by electron photoinjection (EPI) from mercury electrodes and were found to increase dramatically from ≤3 × 103 s-1 (3-F - C6H4CO2-) to (1.2 ± 0.8) × 109 s-1 (C6F5CO2-). The regioselectivity of C-F bond cleavage in the RA fragmentation has been revealed by structure assignment of reduction products of the polyfluorinated benzoic acids by Na, K, and Zn in liquid NH3, as well as by Zn in aqueous NH3 and aqueous alkaline solutions. The kc values depend on the position of the cleaved fluorine to the CO2- group generally in the order para > ortho > meta, and to sharply increase if adjacent fluorine atoms are present. The observed trends reveal that the kinetics of the RA fragmentation reaction is not controlled by the reaction thermodynamics. Semiempirical UHF/INDO calculations, the validity of which has been confirmed by ab initio ROHF/6-31+G calculations, were done to rationalize the observed trends. The reaction transition state (TS) was considered to arise from the RA's and 2*states crossing avoided due to out-of-plane deviation of the cleaving C-F bond. The satisfactory linear correlation (R = 0.96) between the model reaction energy barrier Ea and log kc has been achieved with modeling the local solvation of the CO2- group by its protonation.
- Konovalov, Valery V.,Laev, Sergey S.,Beregovaya, Irina V.,Shchegoleva, Lyudmila N.,Shteingarts, Vitalij D.,Tsvetkov, Yuri D.,Bilkis, Itzhak
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p. 352 - 361
(2007/10/03)
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- Elemental fluorine. Part 1. Synthesis of fluoroaromatic compounds
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Direct fluorination of 4-fluorobenzoic acid, as a model substrate in a variety of reaction media, shows that 98% formic acid and concentrated sulfuric acid are excellent for promoting electrophilic fluorination. A high degree of fluorination may be achieved using concentrated sulfuric acid, showing that in this medium fluorine will act as a powerful electrophile.
- Chambers, Richard D.,Skinner, Christopher J.,Hutchinson, John,Thomson, Julie
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p. 605 - 609
(2007/10/03)
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- 1-phenyl-3-(1-piperazinyl)-1H-indazoles
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Novel 1-phenyl-3-(1-piperazinyl)-1H-indazoles, intermediates and processes for the preparation thereof, and methods for alleviating pain, treating convulsions, and treating depression utilizing compounds or compositions thereof are disclosed.
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