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Synthesis Of Chiral Phosphoric Acid Catalyst and Its Application in Enantioselective Amidoalkylation Reaction of 2,5-Dimethylpyrrole and 5-Hydroxybutyrolactam

Hamzah Shiddiq Saifurofi', Dr. M. Idham Darussalam Mardjan, M.Sc.; Prof. Laurent Commeiras

2023 | Skripsi | KIMIA

Pengembangan sintesis enantioselektif ?-laktam menggunakan katalis asam fosfat kiral telah dilakukan. Penelitian ini bertujuan untuk mensintesis senyawa asam fosfat kiral dan mengaplikasikannya pada reaksi amidoalkilasi enantioselektif senyawa turunan ?-laktam. Penelitian diawali dengan melakukan sintesis senyawa asam fosfat kiral melalui lima tahapan reaksi, meliputi reaksi metilasi, iodinasi, cross-coupling, demetilasi, dan fosforilasi. Senyawa enantioselektif ?-laktam disintesis dari reaksi antara 2,5-dimetilpirol dengan 5-hidroksibutirolaktam menggunakan asam fosfat kiral sebagai katalis. Produk reaksi yang dihasilkan dianalisis menggunakan spektrometer 1H-NMR dan 13C-NMR. Analisis asam fosfat kiral dilakukan menggunakan spektrometer 31P-NMR. Analisis HPLC dilakukan untuk menentukan nilai enantiomeric excess senyawa ?-laktam. 
Hasil penelitian menunjukkan bahwa reaksi metilasi, iodinasi, cross-coupling, demetilasi, dan fosforilasi menghasilkan persen hasil berturut-turut sebesar 52%, 78%, 59%, 99%, dan 78%. Senyawa asam fosfat kiral dapat disintesis dengan total persen hasil sebesar 19?ri lima tahapan reaksi dan didapatkan sebagai senyawa murni melalui metode rekristalisasi. Senyawa enantioselektif 2-isobutil-3-metil-1,2-dihidro-1?H,5H-[2,3?-bipirol]-5-on dapat disintesis menggunakan katalis asam fosfat kiral dan didapatkan persen hasil sebesar 94?ngan enantiomeric excess sebesar 83%. 

Development of enantioselective synthesis of ?-lactam in the presence of chiral phosphoric acid catalyst has been carried out. This research was aimed to synthesize a chiral phosphoric acid and apply it in the enantioselective amidoalkylation reaction of ?-lactam derivative. Initially, chiral phosphoric acid was synthesized from (S)-BINOL in five reaction steps, including methylation, iodination, cross-coupling, demethylation, and phosphorylation reactions. Then, synthesis of enantioenriched ?-lactam was conducted from 5-substituted-hydroxybutyrolactam and 2,5-dimethylpyrrole in the presence of chiral phosphoric acid as catalyst. All of the synthesized compounds were elucidated using 1H-NMR and 13C-NMR spectrometer. Additional analysis of chiral phosphoric acid was carried out using 31P-NMR spectrometer. HPLC analysis was performed to determine the enantiomeric excess of the enantioenriched lactam.
The results showed that the reaction process included methylation, iodination, cross-coupling, demethylation, and phosphorylation reactions obtained the yields of 52%, 78%, 59%, 99%, and 78%, respectively. The chiral phosphoric acid could be synthesized in 19% total yield over five reaction steps and could be obtained as a pure form through recrystallization method. The enantioenriched 2-isobutyl-3-methyl-1,2-dihydro-1?H,5H-[2,3?-bipyrrol]-5-one was successfully synthesized using the synthesized chiral phosphoric acid in 94% yield and 83% ee.

Kata Kunci : Chiral phosphoric acid, enantioselective amidoalkylation reaction, butyrolactam, pyrrole.

  1. S1-2023-424220-abstract.pdf  
  2. S1-2023-424220-bibliography.pdf  
  3. S1-2023-424220-tableofcontent.pdf  
  4. S1-2023-424220-title.pdf