ChemicalBook CAS DataBase List Ethambutol

Ethambutol synthesis

8synthesis methods

Product Name:Ethambutol
CAS Number:74-55-5
Molecular formula:C10H24N2O2
Molecular Weight:204.31

Ethambutol, (±)-N,N-ethylenbis-(2-aminobutan-1-ol) (34.1.4), is synthesized in several different ways. According to one of them, nitropropane undergoes oxymethylation using formaldehyde, and the nitro group in the resulting 2-nitrobutanol (34.1.2) is reduced by hydrogen to an amino group, making racemic (±) 2-aminobutanol. L (＋) tartaric acid is used to separate (＋) 2-aminobutanol (34.1.3). Reacting this with 1, 2-dichloroethane in the presence of sodium hydroxide gives ethambutol (34.1.4).

An alternative method of synthesis consists of preparing (＋) 2-aminobutanol (34.1.3) by reducing ethyl ester of L-2-aminobutyric acid hydrochloride with hydrogen using simultaneously Raney nickel and platinum oxide catalysts. This gives pure (＋) 2-aminobutanol. Reacting this with 1,2-dichloroethane in the presence of sodium hydroxide gives the desired ethambutol (34.1.4).

The third way of synthesis is very interesting and resembles of the Ritter reaction, but which takes place in the presence of chlorine. This method consists of reacting 1-butene and acetonitrile in the presence of chlorine, which evidently results in the 1,4-addition of chlorine to the product of the Ritter reaction, forming an intermediate dichloride (33.1.5), which is hydrolyzed with water to make N-[1-(chloromethyl)-propyl]-acetamide (33.1.6). Heating this product with hydrochloric acid gives racemic (±) 2-aminobutanol, from which (＋) 2-aminobutanol (34.1.3) is isolated as described above using L (＋) tartaric acid. Reacting this with 1,2-dichloroethane in the presence of sodium hydroxide gives the desired ethambutol (34.1.4)