Laboratory Synthesis Of Atenolol

Atenolol IUPAC Chemical Name: 4- [2- hydroxy- 3- [(1- methyl ethyl )amino ]propoxy ]benzene acet amide
Atenolol Use: antiadrenergic (b-receptor), antihypertensive
Atenolol MW: 266.34
Atenolol MF: C14H22N2O3
Atenolol LD50: >57 mg/kg (M, i.v.); 2 g/kg (M, p.o.);77 mg/kg (R, i.v.); 2 g/kg (R, p.o.)

This compound has been obtained by two related ways: 1) The reaction of phenol (I) with formaldehyde gives 4-(hydroxymethyl)phenol (II), which is treated with NaCN in hot DMF to yield 2-(4-hydroxyphenyl)

acetonitrile (III). The hydrolysis of (III) in refluxing ethanol/water, catalyzed by a Pt catalyst affords the corresponding acetamide (IV), which is condensed with an excess of hot epichlorohydrin (V) by means of piperidine gives 2-[4-(2-oxiranylmethoxy)phenyl]acetamide (VI). Finally, the oxirane ring of (VI) is opened with isopropylamine in methanol. 2)The condensation of acetonitrile (III) with epichlorohydrin (V) as before gives the 2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile (VIII), which is treated with isopropylamine (VII) in methanol yielding 2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile (IX). Finally, this compound is hydrolyzed with refluxing ethanol/water catalyzed by a Pt catalyst as before to afford the target acetamide.

for detailed procedure see the follwing references ---
1.Akisanya, J.; et al.; A synthesis of atenolol using a nitrile hydration catalyst. Org Process Res Dev 1998, 2, 4, 274
2. Drugs Fut1976,1,(1):7

Atenolol Reference(s):

1. US 3 663 607 (ICI; 16.5.1972; GB-prior. 21.2.1969).
2. US 3 836 671 (ICI; 17.9.1974; GB-prior. 21.2.1969, 24.9.1969, 18.11.1970 and 19.11.1970).
3. DOS 2 007 751 (ICI; appl. 19.2.1970; GB-prior. 21.2.1969 and 24.9.1969).
4. GB 1 285 038 (ICI; appl. 21.2.1969; valid from 24.9.1969).

alternative synthesis:
GB 1 391 444 (ICI; appl. 13.7.1971; valid from 19.6.1972).
4-hydroxybenzyl cyanide:
GB 1 522 477 (ICI; appl. 13.8.1974; valid from 11.11.1975).
US 4 154 757 (ICI; 15.5.1979; appl. 22.5.1978).

tags-synthesis of drugs,method of preparation of Atenolol,molecular weight  Atenolol, molecular formula of  Atenolol