IAOCAT. .kSESTHETIC .ACTIVITY"
Concentration of test material,
. . .
The value is
at 0.3% concentration, 0.5% irritated t,he eye.
The local anes-
thetic activity of lidocaine at 0.01~~
is li%, and at
Calculated as 100
response (see test).
the methoxy group decreases the potency as in
more sensitive method, ionization constants, was used
to determine minor changes in electron density. In the
series, the pKa values of the a-phenylcinnamic
acids parallel with the carbonyl stretching frequency of
the amino esters and are directly proportional to the
local anesthetic activity.
series, the pK,
values of the acids are inversely proportional to the
local anesthetic activity. The activity of
approximately the same as that of lidocaine \Then
tested by the corneal reflex method.
chlorides were prepared by heating the acids6 with a 10% excess
of thionyl chloride in refluxing benzene for 30 min.
One drop of
pyridine per gram of acid was added to the reaction mixture.
solvent and excess thionyl chloride were removed in a rotatory
evaporator. The acid chloride was dissolved in hexane and the
evaporation repeated. In 3 cases
the acid chlo-
rides were recrystallized from hexane and analyzed (Table I).
This was found to be unnecessary since the crude acid chlorides
afforded good yields of the esters. In most cases the acid chloride
in benzene, when treated with 1 mole of the amino alcohol at
room temperature, afforded the solid ester hydrochloride which
was cwllected by filtration. With
moles of the
amino alcohol were allowed to react with the acid chloride and
t,he solid amino alcohol hydrochloride was removed by filtration.
Melting points were taken on a Fisher-Johns melting point block and
performed in the microanalytical labora-
tory, Department of Chemistry, University of California, 13erkeley. Calif.
The filtrate was washed wit,h water, dried over anhydrous sodium
sulfate, and evaporated to dryness
An et,her solution
of the free ester was treated with dry hydrogen chloride to give
the ester hydrochloride, which was collerted hy filt>ration. When
ethanol, it was converted to the ethyl
ester, m.p. 166-l6i0, confirmed by its identit,y with an aut,hen-
tic sample prepared from the acid chloride and ethanol.
these preparations are in Table I and the analytical
dat,a are in Table 111.