- 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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Paragraph 0135
(2021/01/22)
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- Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control
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The photocatalytic C-F functionalization of highly fluorinated arenes is a powerful method for accessing functionalized multifluorinated arenes. The decisive step in the determining regioselectivity in fluorine functionalization is fluoride fragmentation from the radical anion of the multifluorinated arene. To date, the availability of regioisomers has been dictated by the innate electronics of the fluorinated arene, limiting the synthetic utility of the chemistry. This study investigates the remarkable ability of a strategically located hydrogen bond to transcend the normal regioselectivity of the C-F functionalization event. A significant rate acceleration is additionally observed for hydrodefluorination of fluorines that can undergo intramolecular hydrogen bonds that form 5-8-membered cycles with moderately acidic N-H's. The hydrogen bond is expected to facilitate the fragmentation not only by bending the C-F bond of the radical anion out of planarity but also by increasing the exothermicity of the fluoride extrusion step through protonation of the naked fluoride. Finally, the synthetic utility of the method is demonstrated in an expedited synthesis of the trifluorinated α-phenyl acetic acid derivative required for the commercial synthesis of Januvia, an antidiabetic drug. This represents the first synthesis of a commercially important multifluorinated arene via a defluorination strategy and is significantly shorter than the current strategy.
- Khaled, Mohammad B.,El Mokadem, Roukaya K.,Weaver, Jimmie D.
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supporting information
p. 13092 - 13101
(2017/09/26)
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- Electrophilicity and nucleophilicity of commonly used aldehydes
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The present approach for determining the electrophilicity (E) and nucleophilicity (N) of aldehydes includes a kinetic study of KMNO4 oxidation and NaBH4 reduction of aldehydes. A transition state analysis of the KMNO4 promoted aldehyde oxidation reaction has been performed, which shows a very good correlation with experimental results. The validity of the experimental method has been tested using the experimental activation parameters of the two reactions. The utility of the present approach is further demonstrated by the theoretical versus experimental relationship, which provides easy access to E and N values for various aldehydes and offers an at-a-glance assessment of the chemical reactivity of aldehydes in various reactions. the Partner Organisations 2014.
- Pratihar, Sanjay
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p. 5781 - 5788
(2014/07/22)
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- INHIBITORS OF STEAROYL-COA DESATURASE
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity.
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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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- Process improvements in the synthesis of 2,4,5-trifluorobenzoic acid. selective hydrodefluorination of tetrafluorophthalimides
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An improved preparation of the fluoroquinolone antibacterial intermediate 2,4,5-trifluorobenzoic acid is described. A combination of a selective hydrodefluorination and hydrolysis reaction of 3,4,5,6-tetrafluoro-N-methylphthalimide leading to 3,5,6-trifluorophthalic acid was key to the success of the process. In addition the development of a two-step, one-pot imidization/ halogen exchange from tetrachlorophthalic anhydride to 3,4,5,6-tetrafluoro-N-methylphthalimide in sulfolane solvent is detailed.
- Fertel, Lawrence B.
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p. 111 - 115
(2013/09/08)
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- Process for the preparation of fluorinated benzoic acids
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A process for the preparation of 2-chloro-4,5-difluorobenzoic acid and 2,4,5-trifluorobenzoic acid as well as synthetic intermediates useful in and prepared according thereto, comprising reacting a nitrobenzene having the formula STR1 wherein X is chloro or fluoro, with an appropriate carbanion to form a compound having the formula STR2 wherein one of Y and Z is chloro and the other is nitro, and R is a radical selected from the group consisting of --CCl3, --CH2 NO2, --CH(NO2)R1, --CH(CO2 R1)2, --CH(C(O)R2)2, --CH(CN)CO2 R1, --CH(CO2 R1)COR2 and --COR2 where R1 is alkyl or arylalkyl and R2 is alkyl, aryl or arylalkyl and, where appearing more than once in such a radical, R1 and R2 may be the same or different at each occurrence.
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- Process for the preparation of halogenated benzoic acids
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A process for the preparation of halogenated benzoic acids of formula (1): STR1 in which R1, R2, R3, R4 and R5 are hydrogen, fluorine, chlorine or bromine atoms or C1 -C6 -alkyl, C1 -C6 -alkoxy, nitro, cyano, trifluoromethyl, aidehyde, C1 -C4 -alkoxycarbonyl, -SO2 -C1 -C4 -alkyl, -SO2 -phenyl, -CONH2, -CON(C1 -C4 -alkyl)2, hydroxy, carboxy, -NH2 or -N(C1 -C4 - alkyl)2 groups, at least one of the substituents R1 -R5 being one of said halogen atoms, which comprises reacting 1 mol of a benzophenone, asymmetrically substituted on the benzene rings A and B, of general formula (2): STR2 in which R1 -R10 are as defined above for R1 -R5, with about 1 to about 10 mol of an oxidizing agent selected from the group comprising hydrogen peroxide, urea/hydrogen peroxide addition product, an alkali metal peroxide, ammonium, alkali metal or alkaline earth metal peroxodisulfates, pertungstates, perborates or percarbonates, ozone, alkyl- or aryl-percarboxylic acids, alkyl- or aryl-persulfonic acids or persulfuric acid, at temperatures from about -20° to about +100° C.
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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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- Spiro compound
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The present invention relates to spiro compounds of general formula I: STR1 wherein the substituents are herein below defined. The present invention relates to antibacterial spiro compounds which are of value as drugs for humans, veterinary drugs or drugs for use in fish culture or as preservatives, and to antibacterial compositions containing one or more of the same compounds as active ingredients.
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- Preparation of 2,4,5-trifluorobenzoic acid by decarboxylation of 3,4,6-trifluorophthalic acid
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3,4,6-Trifluorophthalic acid may be decarboxylated in a controlled manner to form 2,4,5-trifluorobenzoic acid by heating the phthalic acid in a dipolar aprotic solvent in the absence of any catalyst.
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- Process for the preparation of fluorinated benzoic acids
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In the process for the preparation of fluorinated benzoic acids of the formula I STR1 in which X and Y, for example, independently of one another denote chlorine or fluorine and X moreover denotes bromine, a fluorinated chloroacetophenone of the formula II STR2 in which Z denotes chlorine or hydrogen, is reacted with a hypohalite.
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- Novel intermediates for the production of 2,4,5-trifluorobenzoyl fluoride
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The present invention comprises compounds of the formulas: STR1 wherein X is Cl or Br. These compounds are useful as intermediaries for the production of 2,4,5-trifluorobenzoic acid and 2,4,5-trifluorobenzoyl fluoride.
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- Synthesis, Antibacterial Activities, and Pharmacological Properties of Enantiomers of Temafloxacin Hydrochloride
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Temafloxacin hydrochloride is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent.It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group.The two enantiomers were synthesized and tested for their antibacterial activities.Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed.However, they both exhibited similar pharmacological profiles.
- Chu, Daniel T. W.,Nordeen, Carl W.,Hardy, Dwight J.,Swanson, Robert N.,Giardina, William J.,et al.
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p. 168 - 174
(2007/10/02)
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- Process for producing trifluorobenzene compounds
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A trifluorobenzene compound represented by the general formula (I): STR1 wherein Z represents a cyano group or a carboxyl group, and a process for producing said compounds.
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- 8-fluoro and 7,8,10-trifluoro-9-(substituted)-6-oxo-6H-benzo(C)quinolizine-5-carboxylic acids
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Novel substituted quinolinecarboxylic acid derivatives of the formula: STR1 wherein R1 is hydrogen, alkali metal, alkaline earth metal or lower alkyl; R2 is hydrogen, benzyl or alkyl(C1 -C3); X is hydrogen or fluoro; which have antibacterial activity, intermediates useful in the preparation of the compounds, methods of producing and using the compounds to treat bacterial infections in animals.
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- Quinolone Antibacterial Agents. Synthesis and Structure-Activity Relationships of 8-Substituted Quinoline-3-carboxylic Acids and 1,8-Naphthyridine-3-carboxylic Acids
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A series of 7,8-disubstituted 1-cyclopropyl-6-fluoroquinoline-3-carboxylic acids, 7-substituted 1-cyclopropyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids, and 10-substituted 9-fluoropyridobenzoxazine-6-carboxylic acids has been prepared and evaluated for antibacterial activity.The side chains examined at the 7-position (benzoxazine 10-position) included piperazinyl (g), 3-aminopyrrolidinyl (a), 3-(aminomethyl)pyrrolidinyl (b), and alkylated 3-(aminomethyl)pyrrolidinyl (c-f).Variations ta C-8 of the quinolone ring system included hydrogen, nitro, amino, fluorine and chlorine.The relative enhancement of in vitro activities by the side chains on the 8-hydrogen quinolone and 1,8-naphthyridine against Gram-negative organisms was a > b > g > c-f.The activity imparted to the substituted quinolone nucleus by the 8-substituent was in the order F > Cl > naphthyridine > H > benzoxazine > NH2 > NO2.These trends were retained in vivo.
- Sanchez, Joseph P.,Domagala, John M.,Hagen, Susan E.,Heifetz, Carl L.,Hutt, Marland P.,et al.
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p. 983 - 991
(2007/10/02)
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