Atenolol
Synthesis and Physical Properties of Atenolol
Source: Ali, O., Obaid, R., Saify, Z & Ahmed, S. (2005). Biopharmaceutical Evaluation of Oral Tablet Atenolol (100 and 50 mg) on Local Population. Pakistan Journal of Pharmaceutical Sciences, 18(1), 25-32
Atenolol is defined to be a “beta1-selective cardioselective beta-adrenergic receptor blocking agent without membrane stabilizing or intrinsic sympathomimetic activities. Higher doses of this drug inhibits the beta 2- adrenoreceptors 1”. Atenolol has the molecular formula of C14H22N2O3. Its molecular mass is 266.3 grams and its IUPAC name is (RS)-4-(2-hydroxy-3-isopropylaminopropoxy) phenylacetamide. Its melting point 152-155 degrees Celsius, has a dissociation constant (pKa) of 9.6 at 24 degrees Celsius. It is soluble in water, ethanol and methanol but it is insoluble in ether 2.Atenolol can be synthesized in two parts. The first synthesis is with the reaction of phenol and formaldehyde to form the 4-(hydroxymethyl)phenol the second is treating the 4-(hydroxymethyl)phenol compound with NaCN in hot DMF to form the product of 2-(4-hydroxyphenyl)acetonitrile. Then 2-(4-hydroxyphenyl)acetonitrile will be refluxed with H2O and Ethanol. After the hydrolysis with water and ethanol, this compound will be catalysed using a Pt catalyst which forms the product of acetamide then condensed with hot piperidine gives 2-[4-(2-oxiranylmethoxy)phenyl]acetamide. Then the oxirane ring of 2-[4-(2-oxiranylmethoxy)phenyl]acetamide is opened using isopropylamine in methanol. The condensation of acetonitrile with epichlorohydrin as before gives the 2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile which is then treated with isopropylamine in methanol yielding 2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile. This compound is hydrolyzed with refluxing ethanol/water catalyzed by a Pt catalyst as before to afford the target acetamide3.
References:
1 Atenolol tablet Retrieved from
Source: Ali, O., Obaid, R., Saify, Z & Ahmed, S. (2005). Biopharmaceutical Evaluation of Oral Tablet Atenolol (100 and 50 mg) on Local Population. Pakistan Journal of Pharmaceutical Sciences, 18(1), 25-32
Atenolol is defined to be a “beta1-selective cardioselective beta-adrenergic receptor blocking agent without membrane stabilizing or intrinsic sympathomimetic activities. Higher doses of this drug inhibits the beta 2- adrenoreceptors 1”. Atenolol has the molecular formula of C14H22N2O3. Its molecular mass is 266.3 grams and its IUPAC name is (RS)-4-(2-hydroxy-3-isopropylaminopropoxy) phenylacetamide. Its melting point 152-155 degrees Celsius, has a dissociation constant (pKa) of 9.6 at 24 degrees Celsius. It is soluble in water, ethanol and methanol but it is insoluble in ether 2.Atenolol can be synthesized in two parts. The first synthesis is with the reaction of phenol and formaldehyde to form the 4-(hydroxymethyl)phenol the second is treating the 4-(hydroxymethyl)phenol compound with NaCN in hot DMF to form the product of 2-(4-hydroxyphenyl)acetonitrile. Then 2-(4-hydroxyphenyl)acetonitrile will be refluxed with H2O and Ethanol. After the hydrolysis with water and ethanol, this compound will be catalysed using a Pt catalyst which forms the product of acetamide then condensed with hot piperidine gives 2-[4-(2-oxiranylmethoxy)phenyl]acetamide. Then the oxirane ring of 2-[4-(2-oxiranylmethoxy)phenyl]acetamide is opened using isopropylamine in methanol. The condensation of acetonitrile with epichlorohydrin as before gives the 2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile which is then treated with isopropylamine in methanol yielding 2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile. This compound is hydrolyzed with refluxing ethanol/water catalyzed by a Pt catalyst as before to afford the target acetamide3.
References:
1 Atenolol tablet Retrieved from
References: 1 Atenolol tablet Retrieved from http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1cc22d45-f09a-49e1-896c-01ef9f80822f#nlm34089-3 (Accessed April 15, 2013) 2 Ali, O., Obaid, R., Saify, Z & Ahmed, S. (2005). Biopharmaceutical Evaluation of Oral Tablet Atenolol (100 and 50 mg) on Local Population. Pakistan Journal of Pharmaceutical Sciences, 18(1), 25-32 3 Atenolol Synthesis Retrieved from http://homepage.ntlworld.com/bhandari/Imperial/Atenolol/Synthesis.htm (Accessed April 15, 2013)