3964-58-7Relevant articles and documents
In vitrocharacterization of 3-chloro-4-hydroxybenzoic acid building block formation in ambigol biosynthesis
Kresna, I Dewa Made,Linares-Otoya, Luis,Milzarek, Tobias,Duell, Elke R.,Mir Mohseni, Mahsa,Mettal, Ute,K?nig, Gabriele M.,Gulder, Tobias A. M.,Sch?berle, Till F.
, p. 2302 - 2311 (2021/03/24)
The cyanobacteriumFischerella ambiguais a natural producer of polychlorinated aromatic compounds, the ambigols A-E. The biosynthetic gene cluster (BGC) of these highly halogenated triphenyls has been recently identified by heterologous expression. It consists of 10 genes namedab1-10. Two of the encoded enzymes,i.e.Ab2 and Ab3, were identified byin vitroandin vivoassays as cytochrome P450 enzymes responsible for biaryl and biaryl ether formation. The key substrate for these P450 enzymes is 2,4-dichlorophenol, which in turn is derived from the precursor 3-chloro-4-hydroxybenzoic acid. Here, the biosynthetic steps leading towards 3-chloro-4-hydroxybenzoic acid were investigated byin vitroassays. Ab7, an isoenzyme of a 3-deoxy-7-phosphoheptulonate (DAHP) synthase, is involved in chorismate biosynthesis by the shikimate pathway. Chorismate in turn is further converted by a dedicated chorismate lyase (Ab5) yielding 4-hydroxybenzoic acid (4-HBA). The stand alone adenylation domain Ab6 is necessary to activate 4-HBA, which is subsequently tethered to the acyl carrier protein (ACP) Ab8. The Ab8 bound substrate is chlorinated by Ab10 inmetaposition yielding 3-Cl-4-HBA, which is then transfered by the condensation (C) domain to the peptidyl carrier protein and released by the thioesterase (TE) domain of Ab9. The released product is then expected to be the dedicated substrate of the halogenase Ab1 producing the monomeric ambigol building block 2,4-dichlorophenol.
Synthesis method of 3-chloro-4-hydroxybenzoic acid
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Paragraph 0012-0016, (2019/11/04)
The invention discloses a synthesis method of 3-chloro-4-hydroxybenzoic acid. The method comprises the following steps: 1) adding an alkali and water into a reaction flask, performing stirring for dissolving, heating the obtained solution to 80-90 DEG C, dropwise adding 3-chloro-4-hydroxytrifluoromethylbenzene into the reaction flask, and continuously carrying out a reaction at 90-100 DEG C for 2-3 h after the completion of the drop-by-drop addition; or adding the alkali and water into the reaction flask, performing stirring for dissolving,, once adding the 3-chloro-4-hydroxytrifluoromethylbenzene into the reaction flask at room temperature, raising the temperature to 90-100 DEG C, and carrying out a reaction for 2-5 h; and 2) cooling the obtained solution to 30-40 DG C after the reactionis finished, filtering the cooled solution, slowly dropwise adding sulfuric acid or hydrochloric acid to the obtained filtrate to adjust the pH value to 1-2 in order to precipitate a solid, filteringthe obtained solution, washing the precipitate with water, and drying the washed precipitate to obtain a colorless solid which is the 3-chloro-4-hydroxybenzoic acid. The raw materials of the present invention are readily available; and the reaction is carried out directly in water, and does not involve organic solvents, so the cost is low.
A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids
Knaus, Tanja,Tseliou, Vasilis,Humphreys, Luke D.,Scrutton, Nigel S.,Mutti, Francesco G.
supporting information, p. 3931 - 3943 (2018/09/11)
Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.
Banana-shaped liquid crystals based on 2,7-dihydroxynaphthalene derivatives
Derkach,Novikova,Gorecka
, p. 577 - 583 (2015/05/13)
Abstract New mono- and dichloro-substituted derivatives of 2,7-dihydroxynaphthalene were synthesized, and their mesomorphic properties were investigated. Bis-2,7-[4-(4-n-alkoxybenzoyloxy)-3-chlorobenzoyloxy]-naphthalenes with the terminal nonyloxy or decyloxy group were found to form nematic and B1 mesophases; the homolog with dodecyloxy group formed B2 modification exclusively. Bis-2,7-[4-(4-n-alkoxybenzoyloxy)-3,5-dichlorobenzoyloxy]naphthalenes occurred to be non-mesomorphic and vitrified from isotropic liquid.
ORGANIC COMPOUNDS
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Page/Page column 76, (2014/05/24)
Novel benzofuran derivatives are disclosed. The derivatives have S1P1 receptor activity and/or disease modifying activity and find use in the treatment of conditions or diseases associated with the immune, vascular and nervous systems in animals and/or humans
SMALL MOLECULE MALARIAL ALDOLASE-TRAP ENHANCERS AND GLIDEOSOME INHIBITORS
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, (2013/05/21)
In one aspect, the present invention relates to a method of identifying compounds useful in modifying the activity of Aldolase. The method includes providing a first model comprising Aldolase or residues of the amino acid sequence corresponding to SEQ ID NO: 1 said residues being at amino acid positions selected from the group consisting of 10-13, 26, 27, 29, 30, 31, 32, 33, 37, 39, 40, 41, 43, 44, 47, 48, 51, 52, 60, 63, 66, 79, 84, 85, 92, 93, 103, 106-109, 112-117, 138, 142, 146, 148, 151, 153, 179, 182, 183, 185, 186, 194, 196, 197, 198, 199, 208, 226-228, 231- 269, 270, 272, 277-283, 285-289, 294, 295, 297-299, 301-304, 306-310, 312, 313, 316, 317, 319, 321, 323, 326, 330, 344, 345, and 347, providing one or more candidate compounds, evaluating contact between the candidate compounds and the first model to determine which of the one or more candidate compounds have an ability to bind to and/or fit in the first model, and identifying compounds which, based on said evaluating, have the ability to bind to and/or fit in the first model as compounds potentially useful for modifying the activity of Aldolase. The present invention also discloses compounds and compositions which modify the activity of Aldolase, or a complex between Aldolase and TRAP. Methods of treating or preventing malaria, or an infection by apicomplexan organisms are also disclosed.
Kinetics of chlorination of phenol and monosubstituted phenols by t-butyl hypochlorite in aqueous alkaline medium
Moodithaya,Gowda, B. Thimme
, p. 420 - 425 (2007/10/03)
The kinetics of chlorination of the parent and sixteen monosubstituted phenols (2-chloro, 2-methyl, 2-carboxy, 2-nitro, 3-chloro, 3-methyl, 3-carboxy, 4-fluoro, 4-chloro, 4-bromo, 4-methyl, 4-ethyl, 4-methoxy, 4-carboxy, 4-acetyl and 4-nitro) by t-BuOCl have been studied in aqueous alkaline medium. The rates of reactions show first order kinetics each in |t-BuOCl| and |XC 6H4OH| and inverse first order in |OH-|. Variation in either ionic strength or addition of reaction product has no significant effect on the rates of reactions, while lowering of the dielectric constant of the medium increases the rate. The rates are measured at different temperatures and the activation parameters for all the phenols computed. A mechanism involving the electrophilic attack of phenoxide ions by HOCl in the rate determining step is suggested. The rates decrease in the order: 3-CH 3 > 2-CH3 > 4-OCH3 > 4-CH3 > 4-C2H5 > H > 3-Cl > 3-COO- > 4-F > 2-COO- > 4-Br > 2-Cl > 4-Cl > 4-COO- > 4-COCH3 > 2-NO2 > 4-NO2. Hammett equation of the type, log k = -3.44 - 2.35 ρ is found to be valid for substituent effects. The enthalpy and entropy of activation are correlated.
Chlorometabolite production by the ecologically important white rot fungus Bjerkandera adusta
Silk,Aubry,Lonergan,Macaulay
, p. 1603 - 1616 (2007/10/03)
Two strains of the basidiomycete, Bjerkandera adusta (DAOM 215869 and BOS55) produce in static liquid culture, phenyl, veratryl, anisyl and chloroanisyl metabolites (CAM's) (alcohols, acids and aldehydes) as well as a series of compounds not previously known to be produced by Bjerkandera species: 1-phenyl, 1-anisyl, 1-(3-chloro-4-methoxy) and 1-(3,5-dichloro-4-methoxy) propan-1,2-diols, predominantly as erythro diastereomers with 1R, 2S absolute configurations. 1-Anisyl-propan-1,2-diol and 1-(3,5-dichloro-4-methoxy)-propan-1,2-diol are new metabolites for which the names Bjerkanderol A and B, respectively, are proposed. Experiments with static liquid cultures supplied with 13C66- and 13C9-L-phenylalanine showed that all identified aromatic compounds (with the exception of phenol) can be derived from L-phenylalanine. For the aryl propane diols, the 13C label appeared only in the phenyl ring and the benzylic carbon, suggesting a stereoselective re-synthesis from a C7 and a C2-unit, likely aromatic aldehyde and decarboxylated pyruvate, respectively. Other compounds newly discovered to be derived from phenylalanine by this white rot fungus include phenylacetaldehyde and phenylpyruvic, phenylacetic, phenyllactic, mandelic and phenyl glyoxylic (benzoyl formic) acids. For both strains, cultures supplied with Na37Cl showed incorporation of 37Cl in all identified chlorometabolites. Veratryl alcohol and the CAM alcohols, which occur in both strains and can be derived from L-phenylalanine (all 13C-labelled), have reported important physiological functions in this white rot fungus. Possible mechanisms for their formation through the newly discovered compounds are discussed.
Kinetics and mechanism of chlorination of phenol and substituted phenols by sodium hypochlorite in aqueous alkaline medium
Gowda,Mary
, p. 1196 - 1202 (2007/10/03)
The kinetics of chlorination of the parent and thirteen substituted phenols (2-methyl, 2-chloro, 2-carboxy, 3-methyl, 3-chloro, 3-carboxy, 4-methyl, 4-ethyl, 4-chloro, 4-bromo, 4-carboxy, 4-acetyl and 4-nitro phenols) by NaOCl have been studied in aqueous alkaline medium under varying conditions. The rates show first order kinetics each in [NaOCl] and [(X)C6H4(OH)] and inverse first order in [OH-]. Variation in ionic strength of the medium and addition of Cl have no significant effect on the rates of reactions. The rates of the reactions are measured at different temperatures and the activation parameters for all the phenols computed. A mechanism involving the electrophilic attack of the phenoxide ions by NaOCl in the rate determining step has been considered. The values of the pre-equilibrium and the rate determining steps have been calculated for all the phenols. The rates decrease in the order: 3-CH3 >2-CH3 >4-C2H5 = 4-CH3 >phenol >3-COO = 3-Cl > 2-COO >4-COO >2-Cl ? 4-Cl ? 4-Br > 4-COCH3 >4-NO2. Hammett plot of the type, log kobs = -2.88 -3.2980σ is found to be valid. The correlation between the enthalpies and the free energies of activations is reasonably linear with an isokinetic temperature of 300 K. Further, the energies of activation of all the phenols are optimised corresponding to the log A of the parent phenol through the equation, Ea = 2.303 RT (log A - log kobs). Similarly log A values of all the phenols are optimised corresponding to the Ea of PhOH through the equation, log A = log kobs + Ea/2.303RT. Ea increases with the introduction of electron-withdrawing groups into the benzene ring, while the introduction of the electron-releasing groups lowers Ea for the reaction. Similarly log A decreases with the substitution of electron-withdrawing groups, while log A increases on substitution with the electron-releasing groups.
Highly selective oxidative monochlorination to synthesize organic intermediates: 2-Chlorotoluene, 2-chloroaniline, 2-chlorophenol, and 2-chloro-4-methylphenol
Mukhopadhyay, Sudip,Chandnani, Kavita H.,Chandalia, Sampatraj B.
, p. 196 - 200 (2013/09/08)
An alternative manufacturing process scheme was developed to synthesize monochloro-substituted aromatic compounds in high selectivity, involving oxidalive chlorination by using HCI-H2O2. Thus, 2-chlorotoluene, 2-chloroaniline, and 2-chlorophenol were synthesized by oxidative chlorination followed by desulphonation or decarboxylation. Oxidative chlorination of 4-methylbenzenesulphonic acid, 4-methylbenzoic acid, 4-aminobenzoic acid, and 4-hydroxybenzoic acid by using a suitable ratio of reactantr:HCI:H2O2, and their subsequent desulphonation or decarboxylation, gave 60-85% yield of the desired products. Oxidative chlorination of 4-methylphenol by using HCI-H2O2 gave as high as 98% selectivity to the desired 2-chloro-4-methylphenol.
