Laboratory synthesis of Medicinal compounds.
SYNTHESIS OF PROPRANOLOL
To synthesis and find out the percentage yield of Propranolol
REFERENCES
1. Kaiser, C., Jen, T., Garvey, E., Bowen, W.D. (1997). Journal of
Medicinal Chemistry, 20(5), 687-9.
2. Crowther, A.F. & Smith, L.H. (1968). Journal of Medicinal
Chemistry, 11, 1009-13.
3. Jaggers, S. E.; Jones, G. (1978). Journal of Medicinal Chemistry, v. 21, n. 2, p. 182-188.
PRINCIPLE
Propranolol is the most useful nonselective adrenergic antagonist (β1, β2- blocker). Propranolol is used in the treatment of angina and hypertension. By antagonizing the β2-receptor, propranolol possesses serious problems to asthmatic patients. Propranolol presents an aryloxypropanolamine structure and has been synthesized in two steps from α-naphthol, using the route shown below:
1. Kaiser, C., Jen, T., Garvey, E., Bowen, W.D. (1997). Journal of
Medicinal Chemistry, 20(5), 687-9.
2. Crowther, A.F. & Smith, L.H. (1968). Journal of Medicinal
Chemistry, 11, 1009-13.
3. Jaggers, S. E.; Jones, G. (1978). Journal of Medicinal Chemistry, v. 21, n. 2, p. 182-188.
PRINCIPLE
Propranolol is the most useful nonselective adrenergic antagonist (β1, β2- blocker). Propranolol is used in the treatment of angina and hypertension. By antagonizing the β2-receptor, propranolol possesses serious problems to asthmatic patients. Propranolol presents an aryloxypropanolamine structure and has been synthesized in two steps from α-naphthol, using the route shown below:
EXPERIMENTAL
A. Synthesis of epoxide
Transfer 1.25 g (0.0085 mol) of 1-naphthol (PM = 144.18 g/mol), 0.5 g KOH to a round-bottom flask and add ethanol/H2O (9:1). After dissolution, add drop wise 4ml (0.049 moles) of epichlorhydrin (MM = 92.5 g/mol, d = 1.180 g/ml, and e.p. 114 °C). The reaction is left under magnetic stirring at room temperature for 48 h. TLC is carried out in an eluent system (hexane/ethyl acetate 9:1) to monitor the end of the reaction. Remove ethanol by vacuum evaporator. Extract aqueous phase with ethyl ether. The ethyl ether extract is dried with anhydrous sodium sulfate. Filter and remove solvent to obtain the crude brown oil.
A. Synthesis of epoxide
Transfer 1.25 g (0.0085 mol) of 1-naphthol (PM = 144.18 g/mol), 0.5 g KOH to a round-bottom flask and add ethanol/H2O (9:1). After dissolution, add drop wise 4ml (0.049 moles) of epichlorhydrin (MM = 92.5 g/mol, d = 1.180 g/ml, and e.p. 114 °C). The reaction is left under magnetic stirring at room temperature for 48 h. TLC is carried out in an eluent system (hexane/ethyl acetate 9:1) to monitor the end of the reaction. Remove ethanol by vacuum evaporator. Extract aqueous phase with ethyl ether. The ethyl ether extract is dried with anhydrous sodium sulfate. Filter and remove solvent to obtain the crude brown oil.
B. Synthesis of propranolol
Transfer 0.2 g (1.0 mmol) of the crude oil with methanol to a round-bottom flask fitted with a stopper and add 4ml of isopropylamine (47 mmol; 2.78 g; d = 0.694 g/ml). Keep the reaction under temperature control (t = 40 °C), for 2 h. Remove solvents by vacuum evaporator. To the obtained product, add 30ml of 2.0 mol/L HCl and transfer to a separating funnel. Extract with ethyl ether. Transfer the aqueous extract to an Erlenmeyer flask and alkalinize with 32ml, 2.0 mol/L NaOH, in an ice bath (0 °C), with vigorous stirring to precipitate the product. Filter the precipitate, dry in a vacuum desiccator, and recrystallize from petrol ether (boiling point = 65–110 °C). Weigh the solid.
OBSERVATION AND CALCULATIONS
Molecular weight of 1- Naphthol = 144.17g
Molecular weight of propranolol = 259.3 g
Theoretical yield = 2.25 g
Practical yield = ……… g
Percentage yield =
Determine the melting point (reported m.p., 95–96 °C).
RESULTS
At least two products are obtained in the first step reaction; however, it is not necessary to purify the crude oil. The by-product results from nucleophilic attack of potassium salt of 1-naphthol to the formed epoxide. This by-product is removed in the second step by ether extraction. The yield is satisfactory. Spectrometric data analysis is recommended.
Disclaimer: This document is provided to the general public as a courtesy; any individual, institution, or organization who choose to use this document, either in its original or in a modified form, do so at their own risk, author is not liable for injuries or accidents that occur in any lab.
No comments:
Post a Comment