Sintesis senyawa antimalaria (1)-N-Alkil-1,10-Fenantrolium dan 3-(2-Hidroksietil)-2-Metil-1,10-Fenantrolin4-OL
HADANU, Ruslin, Dr. Chairil Anwar
2004 | Tesis | S2 Ilmu KimiaTelah dilakukan sintesis tiga senyawa (1)-N-alkil-1,10-fenantrolinium dan 3-(2-hidroksi-etil)-2- metil-1,10- fenantrolin-4-ol yang diharapkan memiliki khasiat sebagai antimalaria. Ketiga senyawa (1)-N-alkil-1,10-fenantrolinum tersebut adalah (1)-N-metil-1,10-fenantrolinium sulfat, (1)-N-etil-1,10-fenantrolinum sulfat, dan (1)-N-benzil-1,10-fenantrolinium klorida. Ketiga senyawa tersebut disintesis melalui alkilasi 1,10- fenantrolin monohidrat menggunakan dimetil sulfat, dietil sulfat, dan benzil klorida dalam pelarut aseton pada suhu refluks berturut-turut selama 8; 9,5; dan 11 jam. Pada percobaan ini diperoleh senyawa (1)-N-metil-1,10-fenantrolinium sulfat, (1)-N-etil-1,10-fenantrolinium sulfat, dan (1)-N-benzil-1,10-fenantrolinium klorida, berturut-turut dengan rendemen 67,7; 79,8; dan 50,3%. Sintesis senyawa 3-(2-hidroksi-etil)-2-metil-1,10- fenantrolin-4-ol dilakukan dari 8-aminoquinolin dalam dua tahap, yaitu (1) reaksi 8-aminoquinolin dengan 2-asetil–butirolakton dan (2) siklisasi senyawa 3-[1-(quinolin-8- ilamino)-etiliden]- 4,5-dihidro-furan-2-on. Reaksi 8-aminoquinolin dengan 2-asetil–butirolakton dilakukan dengan katalis asam p-toluensulfonat dalam pelarut toluena pada suhu refluks selama 6 jam. Diperoleh 3-[1-(quinolin-8- ilamino)-etiliden]-4,5-dihidrofuran- 2-on dengan rendemen 60,6%. Reaksi siklisasi 3-[1-(quinolin-8-ilamino)- etiliden]-4,5-dihidro-furan-2-on dilakukan dengan katalis H2SO4 dan tween-80 sebagai katalis transfer fasa dalam pelarut kloroform pada suhu refluks selama 4 jam. Reaksi ini menghasilkan 3-(2-hidroksi-etil)-2-metil-1,10- fenantrolin-4-ol dengan rendemen 76,2%. Siklisasi 3-[1-(quinolin-8- ilamino)-etiliden]-4,5-dihidro-furan-2-on juga dilakukan menggunakan PBr3 dalam pelarut kloroform pada suhu refluks, suhu kamar, dan dibawah -5oC selama 4 jam, tetapi hasil yang diperoleh hanya merupakan campuran produk yang sulit diidentifikasi. Analisis produk dilakukan dengan spektroskopi infra merah (IR), spektroskopi proton resonansi magnetik inti (1H-NMR), spektroskopi karbon resonansi magnetik inti (13C-NMR), dan spektroskopi massa (MS).
It has been conducted the synthesis of three compounds of (1)-N-alkyl-1,10- phenanthrolinium and 3-(2-hydroxy-ethyl)-2-methyl-1,10-phenanthroline-4-ol which are expected to posses antimalarial activity. The three (1)-N-alkyl-1,10- phenanthrolinium are (1)-N-methyl-1,10-phenanthrolinum sulfate, (1)-N-ethyl-1,10- phenanthrolinium sulfate and (1)-N-benzyl-1,10-phenanthrolinium chloride. The three compounds were synthesized through alkylation of 1,10-phenanthroline monohydrate with dimethyl sulfate, diethyl sulfate and benzyl cloride in aceton by refluxing at 8; 9.5; and 11 hours, respectively. These reactions afforded (1)-N-methyl-1,10-phenanthrolinium sulfate, (1)-N-ethyl-1,10-phenanthrolinium sulfate, and (1)-N-benzyl-1,10-phenanthrolinium chloride in 67.7; 79.8; and 50.3% yields, respectively. The synthesis of 3-(2-hydroxy-ethyl)-2-methyil-1,10-phenantroline-4-ol was carried out from 8-aminoquinoline in two steps i.e. (1) reaction of 8-aminoquinoline with 2-acetyl-butyrolactone and (2) cyclization of the resulted 3-[1-(quinolin-8- ylamino)-ethylidene]-4,5-dihydro-furan-2-one. The reaction of 8-aminoquinoline with 2-acetyl-butyrolactone was performed in toluene at reflux for 6 hours in the presence of p-toluensulfonic acid as catalyst. This reaction gave 3-[1-(quinolin-8- ilamino)-etiliden]-4,5-dihidro-furan-2-on in 60.6% yield. The cyclization of 3-[1-(quinoline-8-ylamino)-ethyliden]-4,5-dihydro-furan-2-one was conducted in cloroform at reflux for 4 hours in the presence of H2SO4 as catalyst and also tween 80 as phase transfer catalyst to give 3-(2-hydroxy-ethyl)-2-methyl-1,10- phenanthroline-4-ol in 76.2% yield. Cyclization of 3-[1-(quinoline-8-ylamino)- ethyliden]-4,5-dihydro-furan-2-one was also tried using PBr3 in various conditions. However these reactions only gave a mixture of products which were difficult to be identified. Identification of the products were carried out by means of infra red (IR) spectroscopy, proton nuclear magnetic resonance (1H-NMR) spectroscopy, carbon nuclear magnetic resonance (13C-NMR) spectroscopy, and mass spectroscopy (MS).
Kata Kunci : Sintesis Senyawa Anti Malaria,(1),N,Akil,1, 10,Fenantrolinium,3,(2,Hidroksietil),2 Metil,1
