Application Of Ultrasound In Chiral Resolution

Ultrasonic is a kind of frequency above 20000 hz is beyond the scope of the human ear hearing sound waves,its direction,strong penetrating power,and because the cavitation effect produced by ultrasonic irradiation also has been widely used in chemistry.Ultrasonic chemistry is mainly comes from the cavitation effect,bubble burst will lead to the huge energy of liquid concentration and liquid movement of kinetic energy is converted into heat of bubbles,resulting in a local high temperature and high pressure,chemical reaction for the hardware in extreme conditions provides a unique way We use these features of ultrasound to introduce ultrasound into the process of chiral separation,which greatly improves the splitting effect.We have also designed a new resolution concept that has never been reported.Under ultrasound-assisted conditions,The exchange between the racemate and the racemate split salt in the configuration and we call it ultrasound-assisted displacement and resolution.For chiral separation of ondansetron and venlafaxine,under the same conditions,the resolution effect of the ultrasound-assisted permutation resolution method is the best,and only one or two recrystallizations are required to obtain the optically pure substance.Compared with the traditional method,not only greatly improved the splitting efficiency but also greatly reduced the split time.Ondansetron is a tetrahydroindazolone derivative and is currently the drug of choice for the treatment of nausea and vomiting following cytotoxic chemotherapy and radiation therapy.We used the tartrate derivative DTTA as a resolving agent and used the traditional resolution,ultrasound-assisted resolution and ultrasound-assisted displacement resolution to split the ondansetron by hand.The solvent,solvent amount,ultrasonic power,and ultrasonic temperature were used.Ultrasonic time and other conditions were screened to determine the best separation process.We conducted infrared,powder diffraction,and single crystal diffraction analysis of the two diastereomeric salts of ondansetron and preliminary explored their resolution mechanism.The experimental results showed that D-DTTA-(R)-ondansetron salt crystallizes more strongly than D-DTTA-(S)-ondansetron,with ionic and hydrogen bonds to two diastereomeric salts.Stability has a certain influence D-DTTA-(R)-ondansetron salt is more stable than D-DTTA-(S)-ondansetron salt,and D-DTTA-(S)-ondansetron salt is more soluble in solvents,By analyzing single crystal data of D-DTTA-(R)-ondansetron salt,it was found that one resolving agent D-DTTA molecule and another D-DTTA molecule are connected to each other in the form of a hydrogen chain,and then each The resolving agent D-DTTA is connected to an ondansetron molecule in the form of a hydrogen bond to form a chain-like supramolecular structure.Venlafaxine chemical named 1-[2(Dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol is an antidepressant that inhibits the reuptake of both norepinephrine and serotonin.Because of its unique neuropharmacological activity,it is used to treat anxiety,panic disorder and major depressive disorder,In this paper,tartrate derivatives DTTA was used as a resolving agent,and venlafaxine was separated by ultrasonic-assisted displacement and resolution.The optimum conditions for resolution were determined by screening the solvent,ultrasonic power and ultrasonic time.We found that L-DTTA-(S)-venlafaxine salt is crystalline and L-DTTA-(R)-venlafaxine salt is amorphous by powder diffraction,single crystal diffraction,etc.As can be seen from the crystal structures of diastereomeric salts,the more-soluble salt L-DTTA-(R)-venlafaxine forms a columnar supramolecular structure,while the less-soluble salt L-DTTA-(S)-venlafaxine salt appears as multilayered sandwich supramolecular structure which is formed by the superimposition of venlafaxine molecular layer and DTTA molecular layer each other,The interlayer space of the sandwich supramolecule is 9.143 (?),the mole ratio of venlafaxine molecule and DTTA molecule is 2:1 in the L-DTTA-(S)-venlafaxine salt,compared to the equal numbers of venlafaxine molecule and DTTA molecule in the L-DTTA-(R)-venlafaxine salt.