3900-89-8Relevant articles and documents
Preparation method of monohalogenated phenylboronic acid
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Paragraph 0066-0071, (2020/09/20)
The invention relates to the technical field of chemical synthesis, and particularly discloses a preparation method of monohalogenated phenylboronic acid. The preparation method comprises the following steps of: by taking dihalogenated benzene as a raw material and a mixture of lithium salt and alkaline ionic liquid as a catalyst, carrying out Grignard exchange with R1MgCl to generate monohalogenated phenyl magnesium chloride, reacting with B (OR) 3 to generate monohalogenated phenyl borate, and hydrolyzing under acidic conditions to obtain monohalogenated phenylboronic acid. The HPLC (High Performance Liquid Chromatography) content of the monohalogenated phenylboronic acid prepared by the method is greater than 99.5%; the total yield of the product is greater than 80%, the contents of monohalogenated phenylboronic acid and phenyldiboronic acid impurities of another halogen are both less than 0.003%, the requirements of modern fine chemical synthesis are completely met, the raw materials are easily available, the operation is simple, the safety is high, and the industrial production of monohalogenated phenylboronic acid is realized.
Mechanistic insights into boron-catalysed direct amidation reactions
Arkhipenko, Sergey,Sabatini, Marco T.,Batsanov, Andrei S.,Karaluka, Valerija,Sheppard, Tom D.,Rzepa, Henry S.,Whiting, Andrew
, p. 1058 - 1072 (2018/02/07)
The generally accepted monoacyloxyboron mechanism of boron-catalysed direct amidation is brought into question in this study, and new alternatives are proposed. We have carried out a detailed investigation of boron-catalysed amidation reactions, through study of the interaction between amines/carboxylic acids and borinic acids, boronic acids and boric acid, and have isolated and characterised by NMR/X-ray crystallography many of the likely intermediates present in catalytic amidation reactions. Rapid reaction between amines and boron compounds was observed in all cases, and it is proposed that such boron-nitrogen interactions are highly likely to take place in catalytic amidation reactions. These studies also clearly show that borinic acids are not competent catalysts for amidation, as they either form unreactive amino-carboxylate complexes, or undergo protodeboronation to give boronic acids. It therefore seems that at least three free coordination sites on the boron atom are necessary for amidation catalysis to occur. However, these observations are not consistent with the currently accepted 'mechanism' for boron-mediated amidation reactions involving nucleophilic attack of an amine onto a monomeric acyloxyboron intermediate, and as a result of our observations and theoretical modelling, alternative proposed mechanisms are presented for boron-mediated amidation reactions. These are likely to proceed via the formation of a dimeric B-X-B motif (X = O, NR), which is uniquely able to provide activation of the carboxylic acid, whilst orchestrating the delivery of the amine nucleophile to the carbonyl group. Quantum mechanical calculations of catalytic cycles at the B3LYP+D3/Def2-TZVPP level (solvent = CH2Cl2) support the proposal of several closely related potential pathways for amidation, all of which are likely to be lower in energy than the currently accepted mechanism.
Importance of 5/6-aryl substitution on the pharmacological profile of 4?-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1?-biphenyl]-2-carboxylic acid derived PPARγ agonists
Obermoser, Victoria,Mauersberger, Robert,Schuster, Daniela,Czifersky, Monika,Lipova, Marina,Siegl, Monika,Kintscher, Ulrich,Gust, Ronald
supporting information, p. 590 - 603 (2016/12/09)
In this structure-activity relationship study, the influence of aryl substituents at position 5 or 6 on the pharmacological profile of the partial PPARγ agonist 4‘-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1‘-biphenyl]-2-carboxylic acid was investigated. This lead was previously identified as the essential part of telmisartan to induce PPARγ activation. Para-OCH3-phenyl substitution strongly increased potency and efficacy independent of the position. Both compounds represent full agonists because of strong hydrophobic contacts with the amino acid Phe363 in the ligand binding domain. Partial agonists with higher potency than telmisartan or the lead were obtained with OH or Cl substituents at the phenyl ring. Molecular modeling suggested additional hydrogen or halogen bonds with Phe360 located at helix 7. It is assumed that these interactions fix helix 7, thereby promoting a partial agonist conformation of the receptor. The theoretical considerations correlate very well with the results from the luciferase transactivation assay using hPPARγ-LBD as well as those from a time-resolved fluorescent resonance energy transfer (TR-FRET) assay in which the coactivator (TRAP220, PGC-1α) recruitment and corepressor (NCoR1) release pattern was investigated.
