Chemical Properties
White to Off-White Solid
Uses
Semi-synthetic antibiotic related to Penicillin. Antibacterial.
Definition
ChEBI: A hydrate that is the trihydrate form of amoxicillin; a semisynthetic antibiotic, used either alone or in combination with potassium clavulanate (under the trade name Augmentin) for treatment of a variety of bacterial infections.
Description
Amoxicillin was synthesized by Beecham Research Laboratories in 1968. A hydroxyl group was introduced on the benzene ring of ampicillin. Amoxicillin shows about a twofold higher serum concentration than ampicillin when administered orally. It was shown by double-blind comparative studies with ampicillin that amoxicillin was as effective as ampicillin when administered at half the dose of ampicillin.
Originator
Arnoxil,Bencard,UK,1972
Manufacturing Process
Ethyl chlorocarbonate (2.2 ml) was added to an ice cold solution of O,N-dibenzyloxycarbonyl-p-oxy-dl-α-aminophenylacetic acid (10 grams) and
triethylamine (3.85 ml) in dry acetone (193 ml). The mixture was stirred at
0°C for 5 minutes during which triethylamine hydrochloride precipitated. The
suspension was cooled to -30°C and stirred vigorously while adding as rapidly
as possible an ice cold solution of 6-aminopenicillanic acid (5.85 grams) in 3%
aqueous sodium bicarbonate (193 ml), the temperature of the mixture never
being allowed to rise above 0°C. The resulting clear solution was stirred for 30
minutes at 0°C, and then for a further 30 minutes, without external cooling,
and finally extracted with diethyl ether (3 x 200 ml) only the aqueous phase
being retained.
This aqueous solution was brought to pH 2 by the addition of hydrochloric acid
and the 6-(O,N-dibenzyloxycarbonyl-p-oxy-dl-α-
aminophenylacetamido)penicillanic acid so liberated was extracted into diethyl
ether (50 ml and 2 portions of 30 ml). The ether phase was washed with
water (3 x 5 ml) and the water washings were discarded.
Finally, the penicillin was converted to the sodium salt by shaking the ether
solution with sufficient 3% sodium bicarbonate to give a neutral aqueous
phase, separating the latter and evaporating it at low pressure and
temperature below 20°C. The product was finally dried over phosphorus
pentoxide in vacuo to give sodium 6-(O,N-dibenzyloxycarbonyl-p-oxy-dl-α-
aminophenylacetamido)-penicillanate (9.2 grams).
A suspension of palladium on calcium carbonate (36 grams of 5%) in water
(150 ml) was shaken in an atmosphere of hydrogen at room temperature and
atmospheric pressure for 1 hour. A neutral solution of sodium 6-(O,Ndibenzyloxycarbonyl-
p-oxy-dl-α-aminophenylacetamido)penicillanate (9
grams) in water (100 ml) was then added and shaking in hydrogen was
resumed for one hour. The suspension was then filtered and the collected
catalyst was washed well with water without being allowed to suck dry
between washings. The combined filtrate and washings were then brought to
pH 6.5 with dilute hydrochloric acid and evaporated to dryness at reduced
pressure and temperatures below 20°C. The product was finally dried over
phosphorus pentoxide in vacuo to give a solid (5.4 grams) containing 6-(phydroxy-
dl-α-aminophenylacetamido)penicillanic acid.
Brand name
Amoxil (GlaxoSmithKline);
Dispermox (Ranbaxy); Larotid (GlaxoSmithKline);
Trimox (Apothecon) [Name previously used:
Amoxycillin.].
Therapeutic Function
Antibacterial
Synthesis
Amoxicillin trihydrate crystals can be obtained through a malic acid-assisted crystallization framework under optimized conditions (2.5 M malic acid, pH 5.5, 60 min, 1500 rpm), reaching 99.21% purity and 61.82% yield[1].
References
[1]Ergin, M. F., Yaşa, H., & Onar, H. Ç. (2026). Green manufacturing of amoxicillin trihydrate: a malic acid-assisted crystallization framework enhanced by Taguchi–ANN optimization. RSC Advances, 16(16), 14793–14805.
https://doi.org/10.1039/d5ra09898j
