SYNTHESIS OF INTERMEDIATE SALBUTAMOL (SAL) AS ASTHMA DRUGS FROM 4-HYDROXYACETOPHENONE

• Main Author: Ulfa Permata, Rizky
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/67508
• Institution: Institut Teknologi Bandung

Salbutamol is an effective-adrenoceptor stimulator for the treatment of various respiratory diseases including asthma and COPD (chronic obstructive pulmonary disease). Hydroxymethyl compound has been successfully synthesized from 4-hydroxyacetophenone which is an important intermediate for the synthesis of salbutamol. The reaction between formaldehyde and 4-hydroxyacetophenone under acidic condition produces 4 (four) derivates hydroxymethyl compounds, including 4-hydroxy-3-hydroxymethyl acetophenone, 6-acetyl-1,3-benzodioxane, 5-acetyl-2-hydroxybenzyl acetate, and 6-acetyl-8-hydroxymethyl-1,3-benzodioxane. The compound 6-acetyl-1,3-benzodioxane was produced as the dominant compound with yield 47%. The dioxane ring of 6-acetyl-1,3-benzodioxane is stable for bromination reaction using bromine, reduction reaction using sodium borohydride, and amination reaction using tert-butylamine. The bromination reaction to 6-acetyl-1,3-benzodioxane produces 6-bromoacetyl-1,3-benzodioxane with a yield 57%, reduction reaction produced 1-(4H-benzo-1,3-dioxane-6-yl)ethanol with yield 51%, and amination reaction afforded ter-butil N-(2-(4H-1,3-benzodioksan-6-il)-2-oksoetil)formamide produce yield 44%. Intermediate compound of 5-acetyl-2-hydroxybenzyl acetate was brominated and reduced respectively to afford 2-bromo-1-(3-bromo-4-hydroxy-5-(hydroxymethyl)phenyl)ethenone 42% and also 1-(4-hydroxy-3-(methoxymethyl)phenyl)ethenone and the yield percentage was 66%. All product compounds were characterized by 1H-NMR, 13C-NMR, HSQC, and HMBC. Based on these measurements, the compound has been successfully synthesized and accordance as target compound.