Oxolamine
Encyclopedia
Oxolamine is a cough suppressant.
systems all rely on hydroxylamine
for providing a preformed N-O linkage. The preparation of the respiratory anti-inflammatory and antitussive agent oxolamine starts by acylation
of the alkoxide
from the N-hydroxyamidine with 3-chloropropionyl chloride; the presence of the negative charge on oxygen results in the formation of the O-acylated product. Treatment of that intermediate with triethylamine
leads
to cyclization via imine formation to afford the 1,2,4-oxadiazole. Displacement of the terminal chlorine
with diethylamine
gives the corresponding amine oxolamine.
Synthesis
The syntheses of 1,2,4-oxadiazoleOxadiazole
Oxadiazole is a heterocyclic aromatic chemical compound with the molecular formula C2H2N2O. There are four isomers of oxadiazole:1,2,4-Oxadiazole, 1,2,5-oxadiazole, and 1,3,4-oxadiazole are known, but the 1,2,3-isomer is unstable and reverts to the diazoketone tautomer...
systems all rely on hydroxylamine
Hydroxylamine
Hydroxylamine is an inorganic compound with the formula NH2OH. The pure material is a white, unstable crystalline, hygroscopic compound. However, hydroxylamine is almost always provided and used as an aqueous solution. It is used to prepare oximes, an important functional group. It is also an...
for providing a preformed N-O linkage. The preparation of the respiratory anti-inflammatory and antitussive agent oxolamine starts by acylation
Acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
of the alkoxide
Alkoxide
An alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They can be written as RO−, where R is the organic substituent. Alkoxides are strong bases and, when R is not bulky, good nucleophiles and good ligands...
from the N-hydroxyamidine with 3-chloropropionyl chloride; the presence of the negative charge on oxygen results in the formation of the O-acylated product. Treatment of that intermediate with triethylamine
Triethylamine
Triethylamine is the chemical compound with the formula N3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine, for which TEA is also a common abbreviation....
leads
to cyclization via imine formation to afford the 1,2,4-oxadiazole. Displacement of the terminal chlorine
Chlorine
Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...
with diethylamine
Diethylamine
Diethylamine is a secondary amine with the molecular structure CH3CH2NHCH2CH3. It is a flammable, strongly alkaline liquid. It is miscible with water and ethanol. It is a colorless liquid which often appears brown due to impurities...
gives the corresponding amine oxolamine.