Optimasi Sintesis Flutamida (4-Nitro-3-trifluorometil isobutil anilin)

LISA NOVELIA ADISTIA, Dr. Ritmaleni, S.Si

2016 | Skripsi | S1 FARMASI

Flutamida merupakan antiandrogenik yang digunakan sebagai kombinasi obat untuk terapi kanker prostat pada pria.Flutamida dapat disintesis dengan menggunakan 4-nitro-3-trifluorometil anilin dan turunan asam isobutirat.Penelitian ini bertujuan untuk melakukan optimasi sintesis flutamida menggunakan 4-nitro-3-trifluorometil anilin dan turunan asam isobutirat dengan pelarut piridin dan trietilamin. Flutamida disintesis dengan 4-nitro-3-trifluorometil anilin dan turunan asam isobutirat (asam isobutirat, isobutiril klorida, dan anhidrida isobutirat) menggunakan pelarut piridin dan trietilamin pada kondisi refluks dengan suhu 75oC pada penggunaan starting material isobutiril klorida, 90oC pada pada penggunaan starting material anhidrida isobutirat, 90oC dan 140oC pada penggunaan starting material asam isobutirat. Hasil sintesis direkristalisasi menggunakan toluena yg telah dipanaskan dan dimasukan ke dalam ice bath selama 10 menit. Selanjutnya disaring menggunakan corong Buchner dan didiamkan hingga membentuk kristal flutamida murni.Kristal flutamida murni diuji kemurniannya dengan penetapan titik leleh dan Kromatografi Lapis Tipis serta dielusidasi strukturnya menggunakan Kromatografi Gas-Spektrometri Massa. Hasil penelitian menunjukkan bahwa flutamida dapat diperoleh dari reaksi antara anhidrida isobutirat dan 4-nitro-3-trifluorometil anilin menggunakan pelarut piridin, dengan rendemen sebesar 22,33%. Reaksi antara asam isobutirat dan 4-nitro-3-trifluorometil anilin menggunakan pelarut piridin pada suhu 90oC dan 140oC selama 240 menit tidak menghasilkan flutamida. Sedangkan reaksi antara isobutiril klorida dan 4-nitro-3-trifluorometil anilin diperoleh rendemen 73,04% pada penggunaan pelarut piridin dan diperoleh rendemen 6,19% pada penggunaan pelarut trietilamin.

Flutamide is an anti-androgenic used for drug combination in treating prostate cancer. Flutamide can be synthesized using 4-nitro-3-triflouromethyl aniline and derivative of isobutyric acid. The experiment is conducted to optimize the synthesis of flutamide using 4-nitro-3-trifluoromethyl aniline and derivative of isobutyric acid with pyridine and triethylamine as solvent. Flutamide was synthesized using 4-nitro-3-trifluoromethyl aniline and derivative of isobutyric acid (isobutyric acid, isobutyryl chloride and isobutyric anhydride) with pyridine and triethylamine as solvent under reflux condition at 75oC using isobutyryl chloride as starting material, 90oC using isobutyric anhidride as starting material, and 90oC & 140oC using isobutyric acid as starting material. Product of synthesis was recrystallized using toluene. The mixture is filtered using Buchner funnel, kept under room temperature until the pale yellow needle-shaped crystal was obtained. The purity of flutamide crystal was checked using Thin Layer Chromatography and melting point. The structure of flutamide crystal is elusidated using Chromatography Gas- Mass Spectrometry. Result of the experiment showed flutamide can be synthesized using 4-nitro-3-trifluoromethyl aniline and isobutyric anhydride with yield 22,33%. Reaction between 4-nitro-3-trifluoromethyl aniline and isobutyric acid under reflux condition at 90oC & 140oC for 240 minutes can not produced flutamide. The yield obtained from reaction between 4-nitro-3-trifluoromethyl aniline and isobutyryl chloride was 73,04% using pyridine as solvent and 6,19% using triethylamine as solvent.

Kata Kunci : flutamida, anhidrida isobutirat, isobutiril klorida, piridin, trietilamin