Hydrazine polyanions: different strategies in the synthesis of heterocycles
Date
2015-06-10
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Abstract
Hüdrasiini fragmenti võib leida paljudes hästi tuntud värvainete, agrokemikaalide ja ravimite struktuurides. Farmaatsiatööstuses on lämmastikku sisaldavad heterotsüklid erikohal ja C-N sideme moodustamine on seejuures üks laiemalt kasutatavatest reaktsioonitüüpidest. Selle tõttu on tsükliliste hüdrasiini derivaatide süntees märkimisväärse tähtsusega, kuid sobivate sünteesimeetodite puudumise tõttu on paljud neist siiamaani suhteliselt raskesti kättesaadavad ja väheuuritud. Antud töö on keskendunud erinevat tüüpi tsükliliste hüdrasiinide sünteesile ja tutvustab rea uusi sünteesimeetodeid, mis lihtsustavad juurdepääsu nendele unikaalsetele ühenditele.
Uuringu keskseks kohaks on hüdrasiinide polüanioonide tekitamine ja alküülimine. Töö käigus näidati, et hüdrasiinide polüanioonide otsene alküülimine dihalogeniididega sobib nende heterotsüklite sünteesiks, kus N-N side asub väljaspool tsüklit. Lisaks näidati, et polüanioonide strateegia on suurepärane instrument ka tsüklitekke metateesiks vajalike substraatide sünteesiks, mis lähtudes diasendatud hüdrasiinidest avab ligipääsu paljudele heterotsüklitele, kus N-N side on tsükli sees. Hüdrasiinide polüanioone võib edukalt kasutada ka aromaatse sillaga bis(hüdrasiinide) üheetapiliseks sünteesiks. Selliseid ühendeid võib lugeda potentsiaalseteks närvihaiguste ravimite kandidaatideks. Lisaks praktilisele väärtusele, omab see protsess ka suurt teoreetiliselt tähtsust, kuna see hõlmab absoluutselt uut reaktsioonitüüpi, mida pole varem kirjeldatud.
Hydrazine moiety can be found in the structures of many well-known dyes, agrochemicals and drugs. In the pharmaceutical industry nitrogen-containing heterocycles take the special place, and C-N bond formation is one of the most employed reaction types. For that reason, synthesis of cyclic hydrazine derivatives, many of which still remain relatively unachievable and unexplored, is of a significant importance. The current dissertation is focused on the synthesis of different types of cyclic hydrazines and introduces a set of new synthetic methods to simplify an access to these compounds. The central point of the research is formation and alkylation of hydrazine polyanions. It was shown that direct alkylation of hydrazine polyanions with dihalides was applicable for the synthesis of the heterocycles with the N-N bond outside the ring. Polyanion strategy was demonstrated to be an excellent tool for the synthesis of the substrates for ring-closing metathesis from disubstituted hydrazines, thus opening the door to extremely large number of heterocyclic synthetic targets with the N-N bond inside the ring. Also, hydrazine polyanions may be successfully used for a single-step synthesis of aromatic-bridged bis(hydrazines) which may be considered as potential neuroprotective drug candidates. In addition to its practical value, this process may have also a theoretical importance, as it involves an absolutely new reaction type which to the best of our knowledge have never been described before.
Hydrazine moiety can be found in the structures of many well-known dyes, agrochemicals and drugs. In the pharmaceutical industry nitrogen-containing heterocycles take the special place, and C-N bond formation is one of the most employed reaction types. For that reason, synthesis of cyclic hydrazine derivatives, many of which still remain relatively unachievable and unexplored, is of a significant importance. The current dissertation is focused on the synthesis of different types of cyclic hydrazines and introduces a set of new synthetic methods to simplify an access to these compounds. The central point of the research is formation and alkylation of hydrazine polyanions. It was shown that direct alkylation of hydrazine polyanions with dihalides was applicable for the synthesis of the heterocycles with the N-N bond outside the ring. Polyanion strategy was demonstrated to be an excellent tool for the synthesis of the substrates for ring-closing metathesis from disubstituted hydrazines, thus opening the door to extremely large number of heterocyclic synthetic targets with the N-N bond inside the ring. Also, hydrazine polyanions may be successfully used for a single-step synthesis of aromatic-bridged bis(hydrazines) which may be considered as potential neuroprotective drug candidates. In addition to its practical value, this process may have also a theoretical importance, as it involves an absolutely new reaction type which to the best of our knowledge have never been described before.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone.
Keywords
heterotsüklilised ühendid, hüdrasiinid, keemiline süntees, heterocyclic compounds, hydrazines, chemical synthesis