METHOD OF PRODUCTION ω-(BIS(PYRIDINE-2-ILMETHYL)AMINO)ALIPHATIC ACIDS - PRECURSORS WITH HELATERAL CENTERS FOR BINDING METALS Russian patent published in 2017 - IPC C07D213/38 C07D213/55 

FIELD: chemistry.

SUBSTANCE: invention relates to a process for preparing ω-(bis (pyridin-2-ylmethyl)amino)aliphatic acids, which are precursors with chelating centers for metal binding. The process involves the preparation of esters ω-derivatives of aliphatic acids, followed by reaction with a reagent containing a picolyl substituent, and consists of two steps. In the first stage, intermediate synthesis products - esters iodaliphatic ω-carboxylic acids by oxidative cleavage of aliphatic cyclic ketones under the action of hydrogen peroxide in the presence of a catalyst of copper ions and iodine compounds at room temperature. Is subjected to cleavage of cyclic ketones used as catalyst copper (I) chloride, the preparation is carried out at a ratio of cyclic ketones components: hydrogen peroxide: copper (I) chloride=1:5:0.1, with stirring for 10-20 hours in the presence methanolic or ethanolic iodine solutions. The amount of iodine taken in a ratio of cyclic ketone: iodine=1:0.5. Further, a saturated solution of sodium hydrogencarbonate is added to the reaction mass, transferring ω-Iodaliphatic carboxylic acids into the aqueous layer in the form of sodium salts, and their esters are separated by extraction of the aqueous layer with ethyl acetate. The ethyl acetate extraction is then dried with anhydrous sodium sulphate; ethyl acetate is evaporated and esters of -iodo-aliphatic ωcarboxylic acids are obtained. In the second stage in esters ω-iodaliphatic carboxylic acids, the iodine atom is replaced by bis(pyridin-2-ylmethyl)amino group, for which di-2-picolylamine is used. The second step is carried out at a component ratio of ethers ω-iodaliphatic carboxylic acids: di-2-picolylamine: triethylamine=1:1.16:1, respectively, with stirring at 50°C for 24 hours. After that, ethers are isolated ω-(bis(pyridin-2-ylmethyl)amino)aliphatic acids, for which a saturated solution of sodium hydrogen carbonate is added to the reaction mass and extracted with ethyl acetate. The ethyl acetate extract was dried with sodium sulfate anhydrous, ethyl acetate was distilled off, the residue was purified by column chromatography on silica gel using hexane-ethyl acetate (1:1) as the eluent, gradually increasing the gradient of the latter, and ether ω-(bis(pyridin-2-ylmethyl)amino)aliphatic acid. The ester obtained is hydrolyzed in acetonitrile under concentrated hydrochloric acid for 2 hours at a temperature of 50°C, the solvent was distilled off in vacuo to give ω-(bis(pyridin-2-ylmethyl)amino)aliphatic acids, which do not require additional purification.

EFFECT: increase in the yield of these acids.

9 dwg, 16 ex