Sinteza i karakterizacija novih derivata nitrazepama

master's thesis

• Title (english): Synthesis and characterization of novel nitrazepam derivatives
• Author: Danijel Knežević
• Mentor: Branka Zorc (mentor)
• Committee member: Branka Zorc
• Committee member: Ivana Perković
• Committee member: Jelena Filipović-Grčić
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2015-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Nitrazepam je anksiolitik, hipnotik i antikonvulziv iz skupine benzodiazepina. U ovom radu opisana je sinteza 7-nitro-5-fenil-1,3-dihidro-2H-1,3,4-benzotriazepin-2-ona (4) i 7-nitro-5-fenil-3,1,4-benzoksadiazepin-2(1H)-ona (7), dva nova strukturna analoga nitrazepama koji na položaju 3 benzodiazepinskog prstena umjesto metilenske skupine imaju NH skupinu, odnosno atom kisika.
Spoj 4 dobiven je ciklizacijom hidrazona 2, a spoj 7 ciklizacijom oksima 6. Reakcije ciklizacije provedene su pomoću trifozgena. Ciklizacijom su nastali željeni produkti, ali bi reakcijske uvjete još trebalo optimirati kako bi se povećalo iskorištenje i smanjilo nastajanje nusprodukata. Hidrazon 2 priređen je iz komercijalno dostupnog 2-amino-5-nitrobenzofenona (ANB) i hidrazin hidrata, a oksim 6 iz ANB i hidroksilamina. Strukture svih sintetiziranih spojeva potvrđene su uobičajenim spektroskopskim metodama (IR, 1H i 13C NMR, MS).

Abstract (english)

Nitrazepam is anxiolytic, hypnotic and anticonvulsant from benzodiazepine group. In this thesis synthesis of 7-nitro-5-phenyl-1,3-dihydro-2H-1,3,4-benzotriazepin-2-one (4) and 7-nitro-5-phenyl-3,1,4-benzoxadiazepin-2(1H)-one (7) has been described, two novel nitrazepam analogs with -NH- and oxygen atom in position 3 of the benzodiazepine ring.
Compound 4 has been prepared by cyclization of hydrazine 2, while compound 7 by cyclization of oxime 6. Cyclization reactions were performed with triphosgene. In further research, optimization of the reaction conditions is planned in order to obtain higher yields and less byproducts. Hydrazone 2 has been synthesized from commercially available 2-amino-5-nitrobenzophenone (ANB) and hydrazine hydrate, while oxyme 6 from ANB and hyroxylamine. The structures of the compounds were confirmed by usual analytical and spectroscopic methods (IR, 1H, 13C NMR and mass spectroscopy).

• Keywords: nitrazepam; analozi nitrazepama; hidrazon; oksim; ciklizacija; sinteza
• Keywords (english): nitrazepam; nitrazepam analogs; hydrazone; oxyme; cyclization; synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:857866
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2016-01-20 16:07:32