CODE REF AL7CB116

ORGANIC CHEMISTRY

Synthesis of Procaine; novocaine; 2-(diethylamino)ethyl 4-aminobenzoate)

Aymen LABIDI
INSAT, Université de Carthage, Centre Urbain Nord, BP 676, Tunis-Cedex, 1080 Tunis, Tunisia

articleinfo abstract
Article history:
Procaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular
Written 17 November 2019
injection of penicillin, and it is also used in dentistry. Owing to the ubiquity of the trade name Novocain, in some regions,
Revised 17 November 2019 procaine is referred to generically as novocaine. It acts mainly as a sodium channel blocker.[1] Today it is used
Available 20 November 2019 therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion-enhancing, and mood-
Keywords:
enhancing effects
A. Procaine Procaine was first synthesized in 1905, shortly after amylocaine. It was created by the chemist Alfred Einhorn who gave
A. Reduction the chemical the trade name Novocaine, from the Latin nov- (meaning "new") and -caine, a common ending
C. Oxydation for alkaloids used as anesthetics. It was introduced into medical use by surgeon Heinrich Braun. Prior to the discovery
D. Recrystallization of amylocaine and procaine, cocaine was a commonly used local anesthetic. Einhorn wished his new discovery to be used
for amputations, but for this surgeons preferred general anesthesia. Dentists, however, found it very useful.

1. Introduction

primary use for procaine is as an anaesthetic. 2. Experimental details

Procaine is used less frequently today, since more effective
2.1. Synthesis
(and hypoallergenic) alternatives such as lidocaine (Xylocaine) exist.
Procaine can be synthesized in two ways
Like other local anesthetics (such as mepivacaine, and prilocaine),
procaine is a vasodilator, thus is often coadministered
2.2. The first consists of the direct reaction of the 4-aminobenzoic acid
with epinephrine for the purpose of vasoconstriction.
ethyl ester with 2-diethylaminoethanol in the presence of sodium
Vasoconstriction helps to reduce bleeding, increases the duration and
ethoxide.
quality of anesthesia, prevents the drug from reaching systemic
2.3. The second is by oxidizing 4-nitrotoluene to 4-nitrobenzoic acid,
circulation in large amounts, and overall reduces the amount of
which is further reacted with thionyl chloride, the resulting acid
anesthetic required. Unlike cocaine, a vasoconstrictor, procaine does
chloride is then esterified with 2-diethylaminoethanol to give
not have the euphoric and addictive qualities that put it at risk for
Nitrocaine. Finally, the nitro group is reduced by hydrogenation
abuse.
over Raney nickel catalyst
Procaine, an ester anesthetic, is metabolized in the plasma by the Procaine can be synthesized in two way
enzyme pseudocholinesterase through hydrolysis into para-amino
benzoic acid (PABA), which is then excreted by the kidneys into
the urine.
A 1% procaine injection has been recommended for the treatment of
extravasation complications associated with venipuncture, steroids,
and antibiotics. It has likewise been recommended for treatment of
inadvertent intra-arterial injections (10 ml of 1% procaine), as it helps
relieve pain and vascular spasm.

Procaine is an occasional additive in illicit street drugs, such as

cocaine. MDMA manufacturers also use procaine as an additive at
ratios ranging from 1:1 up to 10% MDMA with 90% procaine, which
can be life-threatening

n
Corresponding author. Tel.: 00216 97 53 75 01.
E-mail address aymenlabidi@insat.u-carthage.tn.
2 A. Ghouili et al. / Journal of Physics and Chemistry of Solids 75 (2014) 188–193

References

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