Optically active secondary amine compound, process for producing optically active secondary amine compound and process for producing optically active carboxylic acid by using said compound

Disclosed are optically active secondary amine compounds and salts thereof having the general formula (I): ##STR1## a process for the preparation of the optically active secondary amine compounds and salts thereof, and the use of such compounds. Such compounds exhibit a high resolution power and hence are useful agents for optical resolution.

The present invention relates to novel optically active secondary amine 
compounds and salts thereof having the general formula (I): 
##STR2## 
wherein R.sub.1 represents a naphthyl or cyclohexyl group, or a phenyl 
group optionally substituted by halogen, nitro, lower alkyl or lower 
alkoxy, R.sub.2 represents a lower alkyl group or a benzyl group 
optionally substituted by lower alkyl, R.sub.3 represents a 
p-hydroxyphenyl or 2-hydroxy-3-lower alkoxyphenyl group when R.sub.2 is 
lower alkyl, or R.sub.3 represents a p-hydroxyphenyl group when R.sub.2 is 
benzyl optionally substituted by lower alkyl, and C* represents an 
asymmetric carbon atom. 
This invention also relates to a process for the preparation of said 
optically active secondary amine compounds and salts thereof, and to the 
use of such compounds. 
It is known, for instance, from the disclosure of Japanese Patent 
Application Kokoku Nos. 20382-1971 and 37130-1979 and Japanese Patent 
Application Kokai No. 35540-1988 that a number of optically active primary 
amine compounds, such as .alpha.-phenyl-.beta.-tolylethylamine, 
.alpha.-phenylethylamine, .alpha.-naphthylethylamine and the like, can be 
used as agents for the optical resolution of compounds having carboxylic 
acid groups. 
The present inventors have synthesized various derivatives of the 
above-mentioned optically active amine compounds to investigate the 
properties of these derivatives, and have now found that a specific kind 
of optically active secondary amine compounds, having a hydroxybenzyl 
group bonded to the nitrogen atom, exhibit a resolution ability higher 
than that of the corresponding optically active primary amine compounds, 
and hence are useful agents for the optical resolution. The present 
invention has been accomplished on the basis of the above finding and 
additional extensive studies. 
Thus, according to the present invention, there are provided novel 
optically active secondary amine compounds and salts thereof having the 
general formula (I): 
##STR3## 
wherein R.sub.1 represents a naphthyl or cyclohexyl group, or a phenyl 
group optionally substituted by halogen, nitro, lower alkyl or lower 
alkoxy, R.sub.2 represents a lower alkyl group or a benzyl group 
optionally substituted by lower alkyl, R.sub.3 represents a 
p-hydroxyphenyl or 2-hydroxy-3-lower alkoxyphenyl group when R.sub.2 is 
lower alkyl, or R.sub.3 represents a p-hydroxyphenyl group when R.sub.2 is 
benzyl optionally substituted by lower alkyl, and 
C* represents an asymmetric carbon atom, and also provides a process for 
the preparation of said amine compounds, and the use of such compounds. 
Now, a detailed explanation will be given for the present invention. 
The optically active secondary amine compounds according to the invention 
are represented by the general formula (I). 
Examples of the substituent represented by R.sub.1 include naphthyl, 
cyclohexyl, phenyl, halogen-substituted phenyl such as o-, m- or 
p-chlorophenyl, o-, m- or p-bromophenyl or the like, nitro-substituted 
phenyl such as o-, m- or p-nitrophenyl or the like, lower 
alkyl-substituted phenyl such as o-, m- or p-tolyl, o-, m- or 
p-ethylphenyl, o-, m- or p-propylphenyl or the like, and lower 
alkoxy-substituted phenyl such as o-, m- or p-methoxyphenyl, o-, m- or 
p-ethoxyphenyl, o-, m- or p-propoxyphenyl or the like. 
Examples of the substituents represented by R.sub.2 include lower alkyl 
such as methyl, ethyl, propyl, butyl, pentyl or the like, benzyl, and 
lower alkyl-substituted benzyl such as o-, m- or p-tolylmethyl, o-, m- or 
p-ethylphenylmethyl, o-, m- or p-propylphenylmethyl, o-, m- or 
p-butylphenylmethyl, o-, m- or p-pentylphenylmethyl or the like. 
Examples of the substituents represented by R.sub.3 are p-hydroxyphenyl, 
2-hydroxy-3-methoxyphenyl, 2-hydroxy-3-ethoxyphenyl, 
2-hydroxy-3-propoxyphenyl, 2-hydroxy-3-butoxyphenyl, 
2-hydroxy-3-pentoxyphenyl, etc. 
As representative examples of the compounds according to the invention, 
there may be mentioned N-(p-hydroxybenzyl)-1-phenylethylamine, 
N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine, 
N-(p-hydroxybenzyl)-1-(p-isopropylphenyl)ethylamine, 
N-(p-hydroxybenzyl)-1-(p-nitrophenyl)ethylamine, 
N-(p-hydroxybenzyl)-1-(p-bromophenyl)ethylamine, 
N-(p-hydroxybenzyl)-1-(1-naphthyl)ethylamine, 
N-(p-hydroxybenzyl)-1-cyclohexylethylamine, 
N-(p-hydroxybenzyl)-1-(p-methoxyphenyl)ethylamine, 
N-(2-hydroxy-3-methoxybenzyl)-1-phenylethylamine, 
N-(2-hydroxy-3-methoxybenzyl)-1-(p-tolyl)ethylamine, 
N-(2-hydroxy-3-methoxybenzyl)-1-(p-isopropylphenyl)ethylamine, 
N-(2-hydroxy-3-methoxybenzyl)-1-(p-nitrophenyl)ethylamine, 
N-(2-hydroxy-3-methoxybenzyl)-1-(p-bromophenyl)ethylamine, 
N-(2-hydroxy-3-methoxybenzyl)-1-(1-naphthyl)ethylamine, 
N-(2-hydroxy-3-methoxybenzyl)-1-cyclohexylethylamine, 
N-(2-hydroxy-3-methoxybenzyl)-1-(p-methoxyphenyl)ethylamine, 
N-(p-hydroxybenzyl)-.alpha.-phenyl-.beta.-p-tolylethylamine and the like. 
The optically active secondary amine compounds (I) may be prepared by a 
process, wherein an optically active amine of the general formula (II): 
##STR4## 
wherein R.sub.1, R.sub.2 and C* have the meanings stated above, is reacted 
with a hydroxybenzaldehyde of the general formula (III): 
EQU R.sub.3 --CHO (III) 
wherein R.sub.3 has the meaning stated above, to produce an imine compound 
of the general formula (IV): 
##STR5## 
wherein R.sub.1, R.sub.2, R.sub.3 and C* have the meanings stated above, 
and said imine compound is then subjected to a reduction process. 
Examples of salts of the optically active compounds (I) includes salts of 
the amine compounds with inorganic acids such as hydrochloric acid, 
sulfuric acid, nitric acid and the like. 
In carrying out the reactions of the optically active compounds (II) with 
the hydroxybenzaldehydes (III) to form the imine compounds (IV), it is 
possible to use, as the optically active amine (II), 1-phenylethylamine, 
1-(1-naphthyl)ethylamine, 1-cyclohexylethylamine, 1-(p-tolyl)ethylamine, 
1-(p-isopropylphenyl)ethylamine, 1-(p-nitrophenyl)ethylamine, 
1-(p-bromophenyl)ethylamine, .alpha.-ethylbenzylamine, 
.alpha.-isopropylbenzylamine, 1-(.beta.-naphthyl)ethylamine, 
.alpha.-phenyl-.beta.-p-tolylethylamine, etc. They are known compounds and 
will be easily available. Examples of the hydroxybenzaldehydes (III) 
include p-hydroxybenzaldehyde, 2-hydroxy-3-methoxybenzaldehyde and the 
like. 
Usually, the reaction is carried out in an organic solvent. Examples of 
such solvents include aromatic hydrocarbons such as benzene, toluene, 
xylene, etc., halogenated hydrocarbons such as carbon tetrachloride, 
chloroform, etc., alcohols such as methanol, ethanol, isopropanol and the 
like, and ethers such as diethyl ether, tetrahydrofuran, etc. These 
solvents may be used alone or in the form of a mixture thereof. 
The reaction temperature is generally within 0.degree. to 200.degree. C., 
preferably 0.degree. to 150.degree. C. Usually, the object of the reaction 
will be satisfactorily accomplished if the reaction time is within 0.5 to 
30 hours, preferably 0.5 to 10 hours. 
The imine compounds (IV) thus obtained may be isolated, or may be used in 
the next reaction step without being separated therefrom. 
In the next step, the imine compounds (IV) are reduced so as to produce the 
optically active amine compounds (I). This reduction may generally be 
carried out by using a reducing agent such as metal hydrides, or by 
catalytic hydrogenation. 
In the case of a process using a reducing agent, it is possible to employ 
metal hydrides such as lithium aluminum hydride, sodium borohydride and 
boranes, for instance, diborane, borane-THF, borane-sulfide complexes, 
borane-amine complexes and the like. 
When lithium aluminum hydride or sodium borohydride is used as the reducing 
agent, the amount thereof used may generally be within 0.25 to 5 moles, 
preferably 0.25 to 2 moles per 1 mole of the imine compounds. 
In the case of boranes, they may usually be used within a range of 0.3 to 5 
moles, preferably 0.3 to 3 moles expressed as boron per 1 mole of the 
imine compounds. 
The reduction is generally carried out in a solvent. The solvents should be 
preferably those inert to the reduction, and include, for example, ethers 
such as diethyl ether, diglyme, triglyme, tetrahydrofuran, dioxane, etc., 
aromatic hydrocarbons such as benzene, toluene, xylene, etc., and 
halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane, 
chloroform, etc. These solvents may be used alone or in the form of a 
mixture thereof. 
When effecting the reduction by using sodium borohydride as the reducing 
agent, it is possible to use not only the above-mentioned solvents but 
also lower alcohols. There is no specific limitation in the amount of the 
solvents used. 
The reaction temperature is generally within a range of -50.degree. to 
+100.degree. C., preferably -20.degree. to +100.degree. C. The reaction 
time is not particularly limited. 
After the completion of the reaction, the reaction mixture is decomposed 
with water, acetic acid or an inorganic acid. Then the reaction mixture is 
alkalized, and organic layer is separated under neutral or weakly alkaline 
conditions, which is thereafter concentrated to obtain the optically 
active amine compounds (I). If necessary, it is possible to effect a 
purification operation, including, for instance, a recrystallization, a 
column chromatography using silica gel and the like. 
In the case of the catalytic hydrogenation, use may be made of a reduction 
catalyst, including, for example, Raney nickel, palladium-carbon, platinum 
dioxide, platinum black and the like. These catalysts may be used 
generally within a range of 0.1 to 100% by weight, preferably from 0.5 to 
50% by weight on the basis of the weight of the imine compounds (IV). 
Though the solvent to be used is not particularly restricted. As long as it 
does not paison the catalyst, usually alcohols such as methanol, ethanol, 
etc., ethers such as diethyl ether, tetrahydrofuran, dioxane and the like, 
acetate esters such as ethyl acetate, isoamyl acetate, butyl acetate, 
etc., aromatic hydrocarbons such as benzene, toluene, xylene and the like, 
acetic acid, N-methylpyrrolidone, water, etc. These solvents may be used 
alone or as a mixture thereof. There is no specific limitation in the 
amount of the solvents used. 
The reaction temperature is generally within a range of -30.degree. to 
+150.degree. C., preferably -10.degree. to +100.degree. C. The reaction 
pressure is usually within a range 0 to 100 kg/cm.sup.2, preferably 
between 0 to 50 kg/cm.sup.2. The reaction time is not particularly 
limited. 
After the reduction is carried out in this way, the catalyst is removed by 
filtration, the optically active amine compounds (I) is obtained by 
evaporation of the filtrate. If necessary, it is effect a purification, 
including, for example, a recrystallization and a column chromatography 
using silica gel or the like. 
The compounds (I) according to the invention are useful as agents for the 
optical resolution. For instance, if any one of the compounds according to 
the invention is reacted with (.+-.)-chrysanthemic acid, and if the 
resulting salt is subjected to an optical resolution, then 
(+)-chrysanthemic acid will be obtained. 
Furthermore, if a compound according to the invention is reacted with a 
(.+-.)-.alpha.-substituted phenylacetic acid, for instance, 
(.+-.)-ibuprofen, (.+-.)-naproxen, (.+-.)-flurbiproten, (.+-.)-ketoprofen, 
(.+-.)-2-(4-chlorophenyl)isovaleric acid or the like, 
(.+-.)-cis-permethric acid, (.+-.)-trans-permethric acid, or an 
.alpha.-hydroxy-acid such as (.+-.)-2-hydroxy-4-phenylbutanoic acid, 
(.+-.)-mandelic acid or the like, and if the resulting amine salt is 
thereafter subjected to an optical resolution, then the corresponding 
optically active (+)-.alpha.-transpermethric acid or 
(-)-.alpha.-hydroxy-acid will be obtained. 
As examples of the compounds according to the invention, which are very 
desirable as agents for the optical resolution of (.+-.)-chrysanthemic 
acid, (.+-.)-permethric acid and (.+-.)-2-(4-chlorophenyl)isovaleric acid, 
there may be mentioned (R)-N-(p-hydroxybenzyl)-1-phenylethylamine, 
(R)-N-(p-hydroxybenzyl)-1-naphthylethylamine, 
(S)-N-(p-hydroxybenzyl)-1-cyclohexylethylamine, 
(R)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine, 
(R)-N-(p-hydroxybenzyl)-1-(p-nitrophenyl)ethylamine, 
(R)-N-(p-hydroxybenzyl)-1-(p-bromophenyl)ethylamine, 
(R)-N-(2-hydroxy-3-methoxybenzyl)-1-phenylethylamine, 
(R)-N-(2-hydroxy-3-methoxybenzyl)-1-(p-tolyl)ethylamine, 
(R)-N-(2-hydroxy-3-methoxybenzyl)-1-(p-nitrophenyl)ethylamine, 
(R)-(+)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta.-p-tolylethylamine and the 
like. When the optical resolution of (.+-.)-ketoprofen or (.+-.)-mandelic 
acid is carried out, it is advantageous to use, as agents for the optical 
resolution the compounds according to the invention, with the proviso that 
the compounds used for this purpose should have a steric configuration 
opposite to that of the compounds listed in the above. 
As (.+-.)-chrysanthemic acid, use may be made of (.+-.)-trans-chrysanthemic 
acid or (.+-.)-cis/trans-mixed-chrysanthemic acid generally within a range 
of a cis/trans ratio of 0/100 to 50/50, preferably 0/100 to 40/60. 
An optical resolution of (.+-.)-chrysanthemic acid, (.+-.)-cis-permethric 
acid, (.+-.)-trans-permethric acid, (.+-.)-.alpha.-hydroxy-acid, 
(.+-.)-.alpha.-substituted phenylacetic acid as the like is generally 
carried out in a solvent. Examples of solvents used are aromatic 
hydrocarbons such as benzene, toluene, xylene and the like, aliphatic 
hydrocarbons such as hexane, heptane, etc., alcohols such as methanol, 
ethanol, etc., ketones such as acetone, methyl isobutyl ketone and the 
like, ethers such as tetrahydrofuran, dioxane, etc., and a mixture of 
these solvents as well as a mixture of the solvents with water. 
In carrying out an optical resolution, use is made of the optically active 
amine compounds as the agents for optical resolution within a range of 0.2 
to 1.2 moles, preferably 0.3 to 1.1 moles per 1 mole of 
(.+-.)-chrysanthemic acid, (.+-.)-cis-permethric acid, 
(.+-.)-trans-permethric acid, (.+-.)-.alpha.-hydroxy-acids or 
(.+-.)-.alpha.-substituted phenylacetic acids. 
In the case of the optical resolution of (.+-.)-chrysanthemic acid, 
(.+-.)-cis-permethric acid, (.+-.)-trans-permethric acid and 
(.+-.)-2-(4-chlorophenyl)isovaleric acid, it is possible to carry out a 
process, wherein such a substance is dissolved, together with (R)-isomers 
of the optically active amine compounds (I), in any of the above-mentioned 
solvents, and then kept standing or stirred. The temperature is generally 
within a range of -20.degree. to +150.degree. C., preferably -10.degree. 
to +100.degree. C., with the proviso that when R.sub.1 =cyclohexyl, then 
use is made of (S)-isomers of the amine compounds (I). In the case of the 
optical resolution of (.+-.)-ketoprofen or (.+-.)-mandelic acid, use is 
usually made of (S)-isomers of the amine compounds (I), except that, when 
R.sub.1 =cyclohexyl, then use is made of (R)-isomers of the amine 
compounds (I). 
After that, the crystalline materials thus produced are separated by 
filtration, and decomposed with an acid such as hydrochloric acid, 
sulfuric acid or the like. Thereafter, an extraction operation is carried 
out with organic solvents to give (+)-transchrysanthemic acid, 
(+)-cis-permethric acid, (+)-transpermethric acid, (-)-mandelic acid, 
(+)-.alpha.-substituted phenylacetic acid or the like. On the other hand, 
the aqueous layer is alkalized and subjected to an extraction operation, 
whereby the (R)- or (S)-isomers of the optically active amine compounds 
may be easily recovered for the reuse thereof. 
Alternatively, if the salts thus formed are decomposed with a base such as 
sodium hydroxide or the like, and if the resultant products are then 
extracted with organic solvents under alkaline conditions, then the 
optically active amine compounds may be recovered. On the other hand, the 
aqueous layer is acidified, and then subjected to an extraction operation 
to give (+)-trans-chrysanthemic acid, (+)-cis-permethric acid, 
(+)-trans-permethric acid, (-)-.alpha.-hydroxy-acid, 
(+)-.alpha.-substituted phenylacetic acid or the like. 
The optically active amine compounds of the general formula (I) according 
to the invention have good properties as agents for the optical 
resolution, and are very desirable for the use thereof in industrial 
fields. Furthermore, the optically active amine compounds mentioned above 
can advantageously be prepared according to the invention even on an 
industrial acale. 
Next, the invention will be illustrated in more detail by the Examples. 
However, it should be noted that the invention is not limited only to the 
Examples.

EXAMPLE 1 
9.96 g (0.082 mole) of (R)-(+)-1-phenylethylamine and 10.54 g (0.086 mole) 
of p-hydroxybenzaldehyde were dissolved in 140 ml of ethyl alcohol, and 
the resulting solution was stirred under reflux for 2 hours. The reaction 
mixture was cooled to room temperature, and the crystalline material thus 
formed was separated by filtration to give 13.0 g of 
(-)-N-(p-hydroxybenzylidene)-1-phenylethylamine. Yield: 70.4%. 
m.p. 176.degree.-178.degree. C.; [.alpha.].sub.D.sup.22 -120.7.degree. (C 
1.0, MeOH) 
NMR-spectral data (.delta. ppm, DMSO-d.sub.6) 1.50 (d) 3H; 4.50 (q) 1H; 
6.7-7.8 (m) 9H; 7-7.8 (broad) 1H; 8.34 (s) 1H. 
EXAMPLE 2 
15 g (0.111 mole) of (R)-(+)-(p-tolyl)ethylamine and 14.23 g (0.117 mole) 
of p-hydroxybenzaldehyde were dissolved in 200 ml of ethyl alcohol, and 
the resultant solution was stirred at room temperature for 2 hours and 
then stirred under reflux for 2 hours. The reaction mixture was 
concentrated under reduced pressure to give 27.2 g of a crude crystalline 
product comprising (R)-(-)-N-(p hydroxybenzylidene)-1-(p-tolyl)ethylamine. 
The crude product was recrystallized from ethyl alcohol to obtain 20.6 g 
of the aimed product. Yield: 77.7%. 
m.p. 168.degree.-170.degree. C.; [.alpha.].sub.D.sup.24 -118 0.degree. (C 
1.0, MeOH) 
NMR-spectral data (.delta. ppm, DMSO-d.sub.6) 1.48 (d) 3H; 2.29 (s) 3H; 
4.94 (q) 1H; 6.7-7.8 (m) 9H; 8.28 (s) 1H. 
EXAMPLE 3 
The procedures shown in Example 2 were repeated, except that 5.34 g of 
(R)-(+)-(p-nitrophenyl)ethylamine were used instead of 15 g of 
(R)-(+)-1-(p-tolyl)ethylamine, and that 5.13 g of 
2-hydroxy-3-methoxybenzaldehyde were used instead of 14.23 g of 
p-hydroxybenzaldehyde. 
9.14 g of 
(R)-(-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(p-nitrophenyl)ethylamine 
were obtained. 
Yield: 94.7%. 
m.p. 88.degree.-90.degree. C.; [.alpha.].sub.D.sup.25 -223.0.degree. (C 
1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.66 (d) 3H; 3.94 (s) 3H; 4.67 
(m) 1H; 6.8-7.05 (m) 3H; 7.4-8.35 (m) 4H; 8.49 (s) 1H; 13.6 (s) 1H. 
EXAMPLE 4 
4.44 g (0.0222 mole) of (R)-(+)-1-(p-bromophenyl)ethylamine and 2.85 g 
(0.0233 mole) of p-hydroxybenzaldehyde were dissolved in 30 ml of ethyl 
alcohol, and the solution thus formed was stirred under reflux for 3 
hours. After the completion of the reaction, the reaction mixture was 
concentrated under reduced pressure, and refined by a column 
chromatography using 30 g of silica gel to give 6.75 g of 
(-)-N-(p-hydroxybenzylidene)-1-(p-bromophenyl)ethylamine. 
Yield: 97.9%. 
m.p. 156.degree.-161.degree. C.; [.alpha.].sub.D.sup.25 -87.6.degree. (C 
0.7, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, DMSO-d.sub.6) 1.48 (d) 3H; 4.34 (q) 1H; 
6.75-7.9 (m) 9H; 8.93 (s) 1H. 
EXAMPLE 5 
The procedures shown in Example 4 were repeated, except that 5.32 g of 
(R)-(+)-(p-nitrophenyl)ethylamine were used instead of 4.44 g of 
(R)-(+)-1-(p-bromophenyl)ethylamine, and that the amount of 
p-hydroxybenzaldehyde used was 4.10 g. 
8.62 g of (-)-N-(p-hydroxybenzylidene)-1-(p-nitrophenyl)ethylamine were 
obtained. Yield: 99.7%. 
m.p 118.degree.-119.5.degree. C.; [.alpha.].sub.D.sup.25 -105.3.degree. (C 
1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.65 (d) 3H; 4.63 (q) 1H; 
6.55-7.0 (m) 4H; 7.4-8.3 (m) 9H; 8.31 (s) 1H. 
EXAMPLE 6 
The procedures shown in Example 4 were repeated, except that 7.63 g of 
(S)-(+)-1-cyclohexylethylamine were used instead of 4.44 g of 
(R)-(+)-1-(p-bromophenyl)ethylamine, and that the amount of 
p-hydroxybenzaldehyde used was 7.69 g. 
15.98 g of (+)-N-(p-hydroxybenzylidene)-1-cyclohexylethylamine were 
obtained. Yield: 94.8%. 
m.p. 130.5.degree.-132.degree. C.; [.alpha.].sub.D.sup.25 +122.7.degree. (C 
1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 0.5-2.05 (broad) 11H; 1.29 (d) 
3H; 3.03 (q) 1H; 6.4-7.7 (m) 4H; 8.07 (s) 1H; 9.17 (s) 1H. 
EXAMPLE 7 
The procedures shown in Example 4 were repeated, except that 9.27 g of 
(S)-(+)-1-cyclohexylethylamine were used instead of 4.44 g of 
(R)-(+)-1-(p-bromophenyl)ethylamine, and that 11.64 g of 
2-hydroxy-3-methoxybenzaldehyde were used instead of 4.44 g of 
p-hydroxybenzaldehyde. 
18.59 g of (+)-N-(2-hydroxy-3-methoxybenzylidene)-1-cyclohexylethylamine 
were obtained. 
Yield: 97.6%. 
[.alpha.].sub.D.sup.26 +132.2.degree. (C 1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 0.5-2.0 (broad) 11H; 1.28 (d) 
3H; 3.15 (m) 1H; 3.90 (s) 1H; 6.84 (m) 3H; 8.65 (s) 1H; 14.0-14.8 (broad) 
1H. 
EXAMPLE 8 
The procedures shown in Example 4 were repeated, except that 13.67 g of 
(R)-(+)-1-(1-naphthyl)ethylamine were used instead of 4.44 g of 
(R)-(+)-1-(p-bromophenyl)ethylamine, and that 12.75 g of 
2-hydroxy-3-methoxybenzaldehyde were used instead of 4.44 g of 
p-hydroxybenzaldehyde. 
23.42 g of (-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(1-naphthyl)ethylamine 
were obtained. 
Yield: 96.1%. 
[.alpha.].sub.D.sup.23 -327.9.degree. (C 1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.76 (d) 3H; 3.87 (s) 3H, 5.36 
(q) 1H; 6.6-7.0 (m) 3H; 7.2-8.2 (m) 7H; 8.35 (s) 1H; 13.5-14.5 (broad) 1H. 
EXAMPLE 9 
The procedures shown in Example 4 were repeated, except that 6.76 g of 
(R)-(+)-1-(1-tolyl)ethylamine were used instead of 4.44 g of 
(R)-(+)-1-(p-bromophenyl)ethylamine, and that 7.99 g of 
2-hydroxy-3-methoxybenzaldehyde were used instead of 4.44 g of 
p-hydroxybenzaldehyde. 
12.77 g of (-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(p-tolyl)ethylamine 
were obtained. 
Yield: 94.8%. 
[.alpha.].sub.D.sup.27 -211.7.degree. (C 1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.61 (d) 3H; 2.33 (s) 3H, 3.90 
(s) 3H; 4.53 (q) 1H; 6.7-7.0 (m) 3H; 7.0-7.4 (m) 4H; 8.36 (s) 1H; 
13.4-14.6 (broad) 1H. 
EXAMPLE 10 
The procedures shown in Example 4 were repeated, except that 7.27 g of 
(R)-(+)-1-phenylethylamine were used instead of 4.44 g of 
(R)-(+)-1-(p-bromophenyl)ethylamine, and that 9.58 g of 
2-hydroxy-3-methoxybenzaldehyde were used instead of 4.44 g of 
p-hydroxybenzaldehyde. 
14.58 g of (-)-N-(2-hydroxy-3-methoxybenzylidene)-1-phenylethylamine were 
obtained. Yield: 95.2%. 
[.alpha.].sub.D.sup.27 -215.8.degree. (C 1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.41 (d) 3H; 3.5-4.05 (m) 3H; 
3.90 (s) 3H; 5.5-6.5 (broad) 2H; 6.34-6.9 (m) 3H; 7.32 (s) 5H. 
EXAMPLE 11 
21.13 g (0.1 mole) of (S)-(+)-.alpha.-phenyl-.beta.-p-tolylethylamine 
(optical purity: 98.2%) and 12.82 g (0.105 mole) of p-hydroxybenzaldehyde 
were dissolved in 100 ml of toluene, and the solution thus formed was 
stirred under reflux for 2 hours, while the water formed during the 
reaction was azeotropically distilled off. Then the reaction mixture was 
cooled to room temperature, and the crystalline material thus formed was 
separated by filtration and recrystallized from ethyl acetate to give 
17.09 g of an imine compound as colorless crystals. Yield: 54.2%. 
m.p. 202.degree.-204.degree. C.; [.alpha.].sub.D.sup.25 -129.4.degree. (C 
1.0, EtOH) 
NMR-spectral data (.delta. ppm, DMSO-d.sub.6) 2.25 (s) 3H; 3.10 (d) 2H; 
4.50 (t) 1H; 6.7-7.7 (m) 9H; 7.0 (s) 4H; 8.0 (s) 1H; 8.7-10.5 (broad) 1H. 
EXAMPLE 12 
15.0 g (0.124 mole) of (R)-(+)-1-phenylethylamine and 19.8 g (0.13 mole) of 
2-hydroxy-3-methoxybenzaldehyde were dissolved in 300 ml of ethyl alcohol, 
and the resultant solution was stirred at room temperature for 3 hours, 
and then stirred under reflux for 2 hours. After that, 2.35 g (0.062 mole) 
of sodium borohydride were added at room temperature to the reaction 
mixture, which was then stirred at a temperature of from 30.degree. to 
35.degree. C. for 1 hour, and thereafter stirred at a temperature of from 
55.degree. to 60.degree. C. for 1.5 hours. After the completion of the 
reaction, 50 ml of a 10% hydrochloric acid were added at room temperature. 
The reaction mixture was then concentrated under reduced pressure, and the 
resulting residue was dissolved in 150 ml of water. The aqueous solution 
thus formed was washed with 150 ml of toluene, and the aqueous layer was 
neutralized or weakly alkalized with a 23% aqueous sodium hydroxide 
solution. The toluene layer was washed with water, and concentrated under 
reduced pressure to give 31.41 g of 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-phenylethylamine as oily 
substance. Yield: 98.6%. 
[.alpha.].sub.D.sup.20 +29.6.degree. (C 1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.42 (d) 3H; 3.5-4.05 (m) 3H; 
3.89 (s) 3H; 5.5-6.5 (broad) 2H; 6.35-6.9 (m) 3H; 7.32 (s) 5H. 
EXAMPLE 13 
The procedures of Example 12 were repeated, except that 13.67 g of 
(R)-(+)-1-(1-naphthyl)ethylamine were used instead of 15.0 g of 
(R)-(+)-1-phenylethylamine, and that 12.75 g of 
2-hydroxy-3-methoxybenzaldehyde were employed instead of 19.8 g of 
2-hydroxy-3-methoxybenzaldehyde. 
(R)-(-)-N-(2-hydroxy-3-methoxybenzyl)-1-(1-naphthyl)ethylamine was obtained 
in an amount of 23.67 g. Yield: 96.5%. 
[.alpha.].sub.D.sup.25 -42.5.degree. (C 1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.56 (d) 3H; 3.87 (s) 3H; 4.70 
(q) 1H; 5.68-7.0 (broad) 2H; 6.3-6.9 (m) 3H; 7.1-8.2 (m) 7H. 
EXAMPLE 14 
8.5 g (0.0283 mole) of 
(R)-(-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(p-nitrophenyl)ethylamine 
were dissolved in 150 ml of ethyl alcohol. Then, 0.54 g (0.0143 mole) of 
sodium borohydride was added at room temperature to the reaction mixture, 
which was thereafter stirred at a temperature of from 30.degree. to 
35.degree. C. for 2 hours, and then stirred at a temperature of from 
55.degree. to 60.degree. C. for 2 hours. After the completion of the 
reaction, the reaction mixture was admixed with 30 ml of a 10% 
hydrochloric acid, and then concentrated under reduced pressure. The 
resulting residue was dissolved in 150 ml of water, washed with 100 ml of 
toluene, and separated into individual layers. The aqueous layer was 
neutralized or weakly alkalized with a 20% aqueous sodium hydroxide 
solution, and extracted twice with 100 ml of toluene. The toluene layer 
was washed with water, and concentrated under reduced pressure to give 
7.75 g of (R)-(+)-N-(2-hydroxy- 
3-methoxybenzyl)-1-(p-nitrophenyl)ethylamine as crystalline substance. 
Yield: 90.6%. 
m.p 112.5.degree.-113.5.degree. C.; [.alpha.].sub.D.sup.24 +64.0.degree. (C 
1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.46 (d) 3H; 3.5-4.2 (m) 3H; 
3.9 (s) 3H; 5.0-6.4 (broad) 1H; 6.4-6.9 (m) 3H 7.35-8.4 (m) 4H (s). 
EXAMPLE 15 
The procedures shown in Example 14 were repeated, except that 18.0 g of 
(S)-(+)-N-(2-hydroxy-3-methoxybenzylidene)-1-cyclohexylethylamine were 
used instead of 8.5 g of 
(R)-(-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(p-nitrophenyl)ethylamine. 
16.12 g of (S)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-cyclohexylethylamine 
were obtained as crystalline substance. Yield: 88.0%. 
m.p. 65.degree.-66.degree. C.; [.alpha.].sub.D.sup.23 +3.8.degree. (C 1.0, 
CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 0.7-2.1 (broad) 11H; 1.12 (d) 
3H; 2.64 (q) 1H; 3.89 (s) 3H; 3.9-4.1 (m) 2H; 5.9-6.6 (broad) 2H; 5.5-7.0 
(m) 3H. 
EXAMPLE 16 
The procedures shown in Example 14 were repeated, except that 24.0 g of 
(R)-(-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(1-naphthyl)ethylamine were 
used instead of 8.5 g of 
(R)-(-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(p-nitrophenyl)ethylamine. 
23.69 g of (R)-(-)-N-(2-hydroxy-3-methoxybenzyl)-1-(1-naphthyl)ethylamine 
were obtained. Yield: 98.0%. 
[.alpha.].sub.D.sup.25 -42.5.degree. (C 1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.56 (d) 3H; 3.87 (s) 5H; 4.70 
(q) 1H; 5.4-7.3 (broad) 2H; 6.3-6.9 (m) 3H; 7.1-8.2 (m) 7H. 
EXAMPLE 17 
11.26 g (0.05 mole) of (R)-(-)-N-(p-hydroxybenzylidene)-1-phenylethylamine 
were dissolved in 150 ml of ethyl alcohol. The resulting solution was 
admixed with 0.95 g (0.025 mole) of sodium borohydride at room 
temperature, stirred at a temperature of from 30.degree. to 35.degree. C. 
for 2 hours, and then stirred at a temperature of from 55.degree. to 
60.degree. C. for 2 hours. After the completion of the reaction, 28 ml of 
a 10% hydrochloric acid were added at room temperature to the reaction 
mixture, which was then concentrated under reduced pressure. The residue 
thus obtained was admixed with 50 ml of water, and thereafter neutralized 
or weakly alkalized with a 20% aqueous sodium hydroxide solution. Then an 
extraction operation was carried out twice with 100 ml of chloroform, and 
the chloroform layer was washed with water, dried over sodium sulfate, and 
concentrated under reduced pressure to give 11.34 g of crude 
(R)-(+)-N-(p-hydroxybenzyl)- 1-phenylethylamine. The crude product was 
refined by a column chromatography employing silica gel, so that 10.64 g 
of a refined product were obtained as viscous oil. Yield: 93.6%. 
[.alpha.].sub.D.sup.21 +44.2.degree. (C 1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.39 (d) 3H; 3.54 (s) 2H; 3.83 
(q) 1H; 5.09 (s) 2H; 6.5-7.25 (m) 4H; 7.32 (s) 5H. 
EXAMPLE 18 
The procedures shown in Example 14 were repeated, except that 12.52 g of 
(R)-(-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(p-tolyl)ethylamine were used 
instead of 8.5 g of 
(R)-(-)-N-(2-hydroxy-3-methoxybenzylidene)-1-(p-nitrophenyl)ethylamine. 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-(p-tolyl)ethylamine was obtained as 
crude crystalline product. Yield: 96.9%. The crude product was 
recrystallized from isopropanol to give 8.53 g of a refined product. Yield 
after recrystallization: 69.7%. 
m.p. 87.degree.-88.5.degree. C.; [.alpha.].sub.D.sup.25 +42.3.degree. (C 
1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.43 (d) 3H; 2.34 (s) 3H; 
3.5-4.1 (m) 3H; 3.87 (s) 3H; 5.9-7.3 (broad) 2H; 6.35-6.85 (m) 3H; 7.15 
(s) 4H. 
EXAMPLE 19 
19.0 g (0.0794 mole) of 
(R)-(-)-N-(p-hydroxybenzylidene)-1-(p-tolyl)ethylamine were dissolved in 
200 ml of ethyl alcohol. The resulting solution was admixed with 1.50 g 
(0.04 mole) of sodium borohydride at room temperature, stirred at a 
temperature of from 25.degree. to 30.degree. C. for 1 hours, and then 
stirred at a temperature of from 55.degree. to 60.degree. C. for 1 hours. 
After the completion of the reaction, 47 ml of a 10% hydrochloric acid 
were added at room temperature to the reaction mixture, which was then 
concentrated under reduced pressure. The residue thus obtained was admixed 
with 100 ml of water, and thereafter neutralized or weakly alkalized with 
a 20% aqueous sodium hydroxide solution. Then an extraction operation was 
carried out three times with 100 ml of chloroform, and the chloroform 
layer was washed with water, dried over sodium sulfate, and concentrated 
under reduced pressure to give 18.99 g of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine. Yield: 99.1%. 
m.p. 114.5.degree.-116.degree. C.; [.alpha.].sub.D.sup.24 +47.5.degree. (C 
1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 1.27 (d) 3H; 2.32 (s) 3H; 3.42 
(s) 2H; 3.69 (q) 1H; 6.3-7.4 (broad) 2H; 6.5-7.5 (m) 8H. 
EXAMPLE 20 
6.26 g (0.0206 mole) of (R)-(-)-N-(p-hydroxybenzylidene)- 
1-(p-bromophenyl)ethylamine were dissolved in 50 ml of ethyl alcohol. The 
resulting solution was admixed with 0.39 g (0.0103 mole) of sodium 
borohydride at room temperature, stirred at a temperature of from 
25.degree. to 30.degree. C. for 2 hours, and then stirred at a temperature 
of from 55.degree. to 60.degree. C. for 2 hours. After the completion of 
the reaction, 15 ml of a 10% hydrochloric acid were added at room 
temperature to the reaction mixture, which was then concentrated under 
reduced pressure. The residue thus obtained was neutralized or weakly 
alkalized with a 2% aqueous sodium hydroxide solution. Then an extraction 
operation was carried out three times with 50 ml of chloroform, and the 
chloroform layer was washed with water, dried over sodium sulfate, and 
concentrated under reduced pressure to give 6.14 g of a crude crystalline 
product, which was then recrystallized from toluene, so that 4.67 g of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-bromophenyl)ethylamine were obtained. 
Yield: 74.0%. 
m.p. 110.degree.-112.degree. C.; [.alpha.].sub.D.sup.24 +52.2.degree. (C 
1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, DMSO-d.sub.6) 1.25 (d) 3H; 2.0-2.9 (broad) 
1H; 3.40 (s) 2H; 3.69 (q) 1H; 6.5-7.7 (m) 3H; 8.7-9.6 (broad) 1H. 
EXAMPLE 21 
17.13 g (0.10 mole) of (R)-(+)-naphthylethylamine and 12.82 g (0.105 mole) 
of p-hydroxybenzaldehyde were dissolved in 300 ml of ethyl alcohol, and 
the resultant solution was stirred under reflux for 2 hours. 1.89 g (0.05 
mole) of sodium borohydride were added at room temperature to the reaction 
mixture, which was then stirred at room temperature for 1.5 hours, and 
thereafter stirred under reflux for 1 hour. After the completion of the 
reaction, the reaction mixture was concentrated under reduced pressure. 
The residue thus obtained was admixed with 100 ml of water, and extracted 
twice with 100 ml of ethyl acetate. The ethyl acetate layer was 
concentrated under reduced pressure to give 28.964 g of a crude 
crystalline product, which were then admixed with a 36% hydrochloric acid 
in methanol so as to form a hydrochloride salt of the product. The 
solution was concentrated under reduced pressure, and the residue thus 
formed was admixed with 50 ml of toluene to crystallized out the 
hydrochloride salt, which was then separated off by filtration, and washed 
twice with 50 ml of toluene to obtain 30.42 g of the crystalline product. 
This product was admixed with 100 ml of water, neutralized or weakly 
alkalized with a 20% aqueous sodium hydroxide solution, and extracted 
three times with 200 ml of ethyl acetate. The organic layer was washed 
with water, dried and concentrated under reduced pressure to give 26.99 g 
of (R)-(-)-N-(p-hydroxybenzyl)-1-(1-naphthyl)ethylamine as crystals. 
Yield: 97.3%. 
m.p. 131.5.degree.-133.degree. C.; [.alpha.].sub.D.sup.25 -3.4.degree. (C 
1.0, CHCl.sub.3) 
EXAMPLE 22 
4.50 g (0.02 mole) of the 
(R)-(-)-N-(p-hydroxybenzylidene)-1-phenylethylamine, which had been 
obtained in Example 1, were dissolved in 200 ml of tetrahydrofuran, and 
admixed with 36.4 ml (0.04 mole) of a 1.1M solution of a borane-THF 
complex in tetrahydrofuran. The reaction mixture was stirred at room 
temperature for 8 hours, and thereafter stirred at 50.degree. C. for 2 
hours. 
The reaction mixture was cooled with ice, and admixed with a 10% 
hydrochloric acid to decompose the reaction product. Then the reaction 
mixture was concentrated under reduced pressure, and the resultant residue 
was neutralized with a 20% aqueous sodium hydroxide solution, and 
extracted with chloroform. The organic layer was concentrated under 
reduced pressure, and refined by a silica gel column chromatography to 
give 4.38 g of (R)-(+)-N-(p-hydroxybenzyl)-1-phenylethylamine. Yield: 
96.4%. 
[.alpha.].sub.D.sup.25 +44.1.degree. (C 1.0, CHCl.sub.3) 
EXAMPLE 23 
5.63 g (0.025 mole) of (R)-(-)-N-(P-hydroxybenzylidene)-1-phenylethylamine 
were dissolved in 50 ml of methanol. To this solution was added 5% by 
weight of a 5% Pd/C per the weight of the imine compound in an autoclave, 
and a catalytic hydrogenation reaction was effected under a hydrogen 
pressure of 20 kg/cm.sup.2 at a temperature of from 25.degree. to 
30.degree. C. for 12 hours. After the completion of the reaction, the 
catalyst was separated off by filtration, and the reaction mixture was 
concentrated under reduced pressure to obtain 5.58 g of a crude amine 
product, which were then refined by a silica gel column chromatography, so 
that 5.38 g of (R)-(+)-N-(p-hydroxybenzyl)-1-phenylethylamine were 
obtained. Yield: 94.7%. 
[.alpha.].sub.D.sup.25 +44.2.degree. (C 1.0, CHCl.sub.3) 
EXAMPLE 24 
21.13 g (0.1 mole) of (R)-(-)-.alpha.-phenyl-.beta.-p-tolylethylamine 
(optical purity: 100%) and 12.82 g (0.105 mole) of p-hydroxybenzaldehyde 
were dissolved in 750 ml of ethyl alcohol. The reaction solution thus 
obtained was stirred at room temperature for 3 hours, and then stirred 
under reflux for 1 hour. Thereafter, the reaction solution was admixed at 
room temperature with 1.89 g (0.05 mole) of sodium borohydride, stirred 
for 3 hours, and then stirred under reflux for 1 hour. The reaction 
mixture was admixed with 75 ml of a 10% hydrochloric acid, and then 
concentrated under reduced pressure to give a crude 
(R)-(+)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta.-p-tolylethylamine.cndot.HC 
l salt, which was thereafter neutralized with an aqueous sodium hydroxide 
solution. The resultant solution was concentrated under reduced pressure 
to obtain the crystals, which were then recrystallized from ethyl alcohol, 
so that 20.47 g of 
(R)-(+)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta.-p-tolylethylamine were 
obtained as colorless crystals. Yield: 64.5%. 
m.p. 129.5.degree.-130.degree. C.; [.alpha.].sub.D.sup.25 +21.2.degree. (C 
1.0, CHCl.sub.3) 
NMR-spectral data (.delta. ppm, CDCl.sub.3) 2.29 (s) 3H; 2.94 (d) 2H; 3.49 
(d) 2H; 3.89 (t) 1H; 3.37 (s) 2H; 6.35-6.90 (m) 4H; 6.99 (s) 4H; 7.30 (s) 
5H. 
EXAMPLE 25 
3.15 g (0.01 mole) of the imine compound, which had been obtained in 
Example 11, were dissolved in 100 ml of tetrahydrofuran, and admixed at 
room temperature with 20 ml (0.02 mole) of a 1.0M solution of a borane-THF 
complex in tetrahydrofuran. The reaction mixture was stirred at room 
temperature for 10 hours, and then stirred at 50.degree. C. for 2 hours. 
Then the reaction mixture was cooled with ice, and admixed with a 10% 
hydrochloric acid to effect a decomposition reaction. The reaction mixture 
was thereafter concentrated under reduced pressure, neutralized with an 
aqueous sodium hydroxide solution, and extracted with chloroform to give 
crude crystalline (S)-(-)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta. 
-p-tolylethylamine, which was then recrystallized from ethyl alcohol, so 
that 2.37 g of the aimed product were obtained. Yield: 74.7%. 
m.p. 129.0.degree.-130.degree. C.; [.alpha.].sub.D.sup.25 +19.6.degree. (C 
1.0, CHCl.sub.3) 
EXAMPLE 26 
8.0 g (0.0476 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5) were dissolved in 8.0 g of toluene, and the resulting 
solution was added dropwise to a solution of 6.88 g (0.0285 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine in 72 g of toluene under 
stirring at 70.degree. C. The reaction mixture was cooled to 20.degree. C. 
over 4 hours, and kept at this temperature for 30 minutes to precipitate a 
crystalline material, which was then separated by filtration, washed twice 
with 15 ml of toluene, and again separated by filtration to give 8.46 g of 
a crystalline product. Yield: 43.4%. 
The crystalline product was decomposed with a 2% aqueous sodium hydroxide 
solution, and adjusted to a pH of from 8 to 9. Then an extraction 
operation was carried out twice with 50 ml of toluene, and the organic 
layer was concentrated under reduced pressure to recover 4.93 g of the 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine. 
The aqueous layer was acidified with a 10% hydrochloric acid, extracted 
twice with 50 ml of toluene, and concentrated under reduced pressure to 
give 3.46 g of (+)-trans-chrysanthemic acid. Yield: 43.3%. 
The (+)-trans-chrysanthemic acid thus obtained was converted into an ester 
of (S)-(+)-2-octanol, which was analysed by a gas chromatography. It was 
found that there were the following optical isomers in this ester product: 
0.3% of (+)-cis-isomer, 0.2% of (-)-cis-isomer, 95.4% of (+)-trans-isomer, 
and 9.2% of (-)-transisomer. Yield (D/D): 82.8%. 
EXAMPLES 27-32 
The procedures shown in Example 26 were repeated, except that the cis/trans 
ratio of (.+-.)-cis/trans-chrysanthemic acid was varied, that use was made 
of various optically active amine compounds and various solutions, and 
that the molar ratio of the amine compounds to the chrysanthemic acid was 
varied. 
EXAMPLE 27 
Materials Used in Reaction 
5.7 g (0.0339 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=19.7/80.3); 4.87 g (0.0202 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine; and 28.5 g of toluene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 2.11 g Yield (D/D): 
70.1%. 
The ratio of optical isomers: 1.7% of (+)-cis-isomer, 1.1% of 
(-)-cis-isomer, 93.0% of (+)-trans-isomer, and 4.2% of (-)-trans-isomer. 
EXAMPLE 28 
Materials Used in Reaction 
8.0 g (0.0476 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=0.1/99.9); 6.88 g (0.0285 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine; and 80 g of toluene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 3.49 g. Yield 
(D/D): 86.3%. 
The ratio of optical isomers: 0% of (+)-cis-isomer, 0% of (-)-cis-isomer, 
98.9% of (+)-trans-isomer, and 1.1% of (-)-trans-isomer. 
EXAMPLE 29 
Materials Used in Reaction 
8.0 g (0.0476 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 8.59 g (0.0356 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine; and 80 g of toluene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 3.71 g. Yield 
(D/D): 87.7%. 
The ratio of optical isomers: 0.4% of (+)-cis-isomer, 0.2% of 
(-)-cis-isomer, 94.1% of (+)-trans-isomer, and 5.3% of (-)-trans-isomer. 
EXAMPLE 30 
Materials Used in Reaction 
8.0 g (0.0476 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 6.88 g (0.0285 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine; and 80 g of 
monochlorobenzene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 3.55 g. Yield 
(D/D): 82.9%. 
The ratio of optical isomers: 0.4% of (+)-cis-isomer, 0.2% of (-)-cis 
isomer, 93.1% of (+)-trans-isomer, and 6.3% of (-)-trans-isomer. 
EXAMPLE 31 
Materials Used in Reaction 
8.0 g (0.0476 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 6.88 g (0.0285 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine; and 80 g of methyl 
isobutyl ketone. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 3.40 g. Yield 
(D/D): 82.3%. 
The ratio of optical isomers: 0.3% of (+)-cis-isomer, 0% of (-)-cis-isomer, 
96.5% of (+)-trans-isomer, and 3.2% of (-)-trans-isomer. 
EXAMPLE 32 
Materials Used in Reaction 
8.0 g (0.0476 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 8.17 g (0.0359 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-phenylethylamine; and 64 g of isopropanol. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 2.52 g. Yield 
(D/D): 60.0%. 
The ratio of optical isomers: 0.4% of (+)-cis-isomer, 0.3% of 
(-)-cis-isomer, 94.9% of (+)-trans-isomer, and 4.3% of (-)-trans-isomer. 
EXAMPLE 33 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid and 2.77 g 
(0.01 mole) of (R)-(-)-N-(p-hydroxybenzyl)-1-(1-naphthyl)ethylamine were 
added to 8.4 g of isopropanol, and heated to 70.degree. C. so as to 
dissolve these reactants in the isopropanol. The reaction solution was 
admixed with 1 mg of an 
(R)-(-)-N-(p-hydroxybenzyl)-1-(1-naphthyl)ethylamine salt of 
(+)-trans-chrysanthemic acid, and cooled to 20.degree. C. over 4 hours. 
Then the reaction mixture was kept standing over night. 
1.62 g of the crystalline material thus formed (yield: 36.4%) were 
separated by filtration, and decomposed with a 2% aqueous sodium hydroxide 
solution. The reaction mixture was adjusted to a pH of from 8 to 9, and 
extracted twice with 25 ml of chloroform. The organic layer was 
concentrated under reduced pressure to recover 0.99 g of 
(R)-(-)-N-(p-hydroxybenzyl)-1-(1-naphthyl)ethylamine. 
The aqueous layer was acidified with a 10% sulfuric acid, extracted twice 
with 25 ml of toluene, and concentrated under reduced pressure to give 
0.60 g of (+)-trans-chrysanthemic acid. Yield: 35.7%. 
The (+)-trans-chrysanthemic acid thus obtained was converted into an ester 
of (S)-(+)-2-octanol which was then analysed by a gas chromatography. 
The ratio of the optical isomers: 0.6% of (+)-cis-isomer, 0.3% of 
(-)-cis-isomer, 96.4% of (+)-trans-isomer, and 2.7% of (-)-trans-isomer. 
EXAMPLES 34-37 
The procedures shown in Example 33 were repeated, except that use was made 
of various optically active amine compounds and also various solvents. 
EXAMPLE 34 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 3.06 g (0.01 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-bromophenyl)ethylamine; and 33.6 g of 
isopropanol. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.52 9. Yield 
(D/D): 60.0%. The ratio of optical isomers: 0.4% of (+)-cis-isomer, 0.4% 
of (-)-cis-isomer, 96.6% of (+)-trans-isomer, and 2.6% of 
(-)-trans-isomer. 
EXAMPLE 35 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 2.17 g (0.01 mole) of 
(S)-(+)-N-(p-hydroxybenzyl)-1-cyclohexylethylamine; and 5.0 g of toluene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.62 g. Yield 
(D/D): 65.2%. The ratio of optical isomers: 0.5% of (+)-cis-isomer, 0.3% 
of (-)-cis-isomer, 87.9% of (+)-trans-isomer, and 11.3% of 
(-)-trans-isomer. 
EXAMPLE 36 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 3.06 g (0.01 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-bromophenyl)ethylamine; and 13.9 g of 
methyl alcohol. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.53 g. Yield 
(D/D): 60.6%. The ratio of optical isomers: 0.2% of (+)-cis-isomer, 0.2% 
of (-)-cis-isomer, 95.9% of (+)-trans-isomer, and 3.7% of 
(-)-trans-isomer. 
EXAMPLE 37 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 2.25 g (0.01 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-tolyl)ethylamine; and 126 g of toluene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.69 g. Yield 
(D/D): 80.7%. The ratio of optical isomers: 0.4% of (+)-cis-isomer, 0.3% 
of (-)-cis-isomer, 97.8% of (+)-trans-isomer, and 1.5% of 
(-)-trans-isomer. 
EXAMPLE 38 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5) and 3.02 g (0.01 mole) of 
(R)-(+)-N-(2-hydroxy-3-methoxy-benzyl)-1-(p-nitrophenyl)ethylamine were 
added to 17.0 g of toluene, and heated to 70.degree. C. so as to dissolve 
these reactants in the toluene. The reaction mixture thus formed was 
admixed with 1 mg of an 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-(p-nitrophenyl)ethylamine salt of 
(+)-trans-chrysanthemic acid, and cooled to 20.degree. C. over 4 hours. 
Then the reaction mixture was kept standing over night. 
The crystalline material thus formed was separated off by filtration. The 
amount of the crystalline material obtained was 1.98 g (yield: 42.1%). The 
crystalline material was decomposed with a 1% hydrochloric acid, and then 
an extraction operation was effected twice with 20 ml of toluene. The 
organic layer was concentrated under reduced pressure to give 0.69 g of 
(+)-trans-chrysanthemic acid (yield: 41.1%). 
The aqueous layer was decomposed with a 2% aqueous sodium hydroxide 
solution, adjusted to a pH of from 8 to 9, and extracted twice with 20 ml 
of toluene. The organic layer thus obtained was concentrated under reduced 
pressure to recover 1.22 g of 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-(p-nitrophenyl)ethylamine. 
The (+)-trans-chrysanthemic acid thus obtained was converted into an ester 
of (S)-(+)-2-octanol, which was then analysed by a gas chromatography. The 
analytical results concerning the optical isomers were as follows: 1.7% of 
(+)-cis-isomer, 0% of (-)-cis-isomer, 96.8% of (+)-trans-isomer, and 1.5% 
of (-)-trans-isomer. Yield (D/D): 80.9%. 
EXAMPLES 39-43 
The procedures shown in Example 38 were repeated, except that use was made 
of various optically active amine compounds and also various solvents. 
EXAMPLE 39 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 2.71 g (0.01 mole) of 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-phenylethylamine; and 9.7 g of 
toluene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.57 g. Yield 
(D/D): 65.9%. The ratio of optical isomers: 0.5% of (+)-cis-isomer, 0.2% 
of (-)-cis-isomer, 96.6% of (+)-trans-isomer, and 2.8% of 
(-)-trans-isomer. 
EXAMPLE 40 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 2.72 g (0.01 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)ethylamine; and 60 g of toluene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.69 g. Yield 
(D/D): 80.6%. The ratio of optical isomers: 1.0% of (+)-cis-isomer, 0.3% 
of (-)-cis-isomer, 97.1% of (+)-trans-isomer, and 1.6% of 
(-)-trans-isomer. 
EXAMPLE 41 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 2.72 g (0.01 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-(p-nitrophenyl)ethylamine; and 12.1 g of 
isopropanol. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.63 g. Yield 
(D/D): 71.9%. The ratio of optical isomers: 0.7% of (+)-cis-isomer, 0.5% 
of (-)-cis-isomer, 95.1% of (+)-trans-isomer, and 3.8% of 
(-)-trans-isomer. 
EXAMPLE 42 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 3.02 g (0.01 mole) of 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-(p-tolyl)ethylamine; and 6.4 g of 
toluene. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.52 g. Yield 
(D/D): 59.8%. The ratio of optical isomers: 0.7% of (+)-cis-isomer, 0.2% 
of (-)-cis-isomer, 95.9% of (+)-trans-isomer, and 3.2% of 
(-)-trans-isomer. 
EXAMPLE 43 
Materials Used in Reaction 
1.68 g (0.01 mole) of (.+-.)-cis/trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5); 3.02 g (0.01 mole) of 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-(p-tolyl)ethylamine; and 8.6 g of 
isopropanol. 
Product 
The amount of (+)-trans-chrysanthemic acid obtained was 0.52 g. Yield 
(D/D): 60.7%. The ratio of optical isomers: 0.8% of (+)-cis-isomer, 0% of 
(-)-cis-isomer, 97.3% of (+)-trans-isomer, and 1.9% of (-)-trans-isomer. 
EXAMPLE 44 
1.68 g (10 millimoles) of (.+-.)-cis-trans-mixed chrysanthemic acid 
(cis/trans=4.5/95.5) and 3.17 g (10 millimoles) of 
(R)-(+)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta.-p-tolylethylamine were 
added to 43.92 g of toluene, and heated to 70.degree. C. so as to dissolve 
these reactants in the toluene. Thereafter, a cooling operation was 
started for the reaction mixture. At 50.degree. C., about 1 mg of an 
(R)-(+)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta.-p-tolylethylamine salt of 
(+)-trans-chrysanthemic acid was added to the reaction mixture, which was 
then cooled to 20.degree. C. over 2 hours, and thereafter kept standing 
over night. 
2.30 g of the crystalline material thus formed were separated by filtration 
(yield: 47.4%), and decomposed with a 2% aqueous sodium hydroxide 
solution. Then an extraction operation was effected three times with 40 ml 
of toluene. The organic layer was concentrated under reduced pressure to 
recover 1.50 g of 
(R)-(+)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta.-p-tolylethylamine. The 
aqueous layer was acidified with 7 ml of a 10% hydrochloric acid, 
extracted with 20 ml of toluene, and concentrated under reduced pressure 
to give 0.79 g of (+)-trans-chrysanthemic acid. Yield: 47.0%. Yield (d/d): 
91.3%. 
The (+)-trans-chrysanthemic acid thus obtained was converted into an ester 
of (S)-(+)-2-octanol, which was analysed by a gas chromatography. The 
analytical results concerning the optical isomers were as follows: 1.3% of 
(+)-cis-isomer, 0.6% of (-)-cis-isomer, 95.8% of (+)-trans-isomer, and 
2.3% of (-)-trans-isomer. 
EXAMPLES 45-47 
The procedures shown in Example 44 were repeated, except that the cis/trans 
ratio of (.+-.)-cis/trans-chrysanthemic acid was varied, and that the 
molar ratio of (.+-.)-cis/trans-chrysanthemic acid to 
(R)-(+)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta.-p-tolylethylamine was also 
varied. The results of these experiments are shown in Table 1. 
TABLE 1 
__________________________________________________________________________ 
Amount used (g) (+)-chrysanthemic acid 
Optically Amount 
Ratio of optical isomers 
Ex. 
(.+-.)-chrysan- 
active obtained (+)- 
(-)- 
No. 
themic acid 
amine Solvent 
(g) (+)-cis 
(-)-cis 
trans 
trans 
__________________________________________________________________________ 
44 1.68 3.17 Toluene 
0.79 1.3 0.6 95.6 
2.3 
(10 mmol) 
(10 mmol) 
43.92 
(Y(d/d) =* 
(cis/trans = 91.3%) 
4.5/95.5) 
45 0.84 0.79 Toluene 
0.36 0.7 0.4 97.6 
1.3 
(5 mmol) 
(2.5 mmol) 
12.60 
(Y(d/d) = 
(cis/trans = 84.3%) 
4.5/95.5) 
46 0.84 1.58 Toluene 
0.30 5.5 2.7 90.8 
1.0 
(5 mmol) 
(5 mmol) 
12.60 
(Y(d/d) = 
(cis/trans = 68.8%) 
20.3/79.7) 
47 1.68 3.17 Toluene 
0.81 -- -- 97.4 
2.6 
(10 mmol) 
(10 mmol) 
44.0 (Y(d/d) = 
(cis/trans = 93.9%) 
0/100) 
__________________________________________________________________________ 
*Y(d/d) . . . Yield (d/d) 
EXAMPLE 48 
2.13 g (0.01 mole) of (.+-.)-2-(4-chlorophenyl)-isovaleric acid and 2.57 g 
(0.01 mole) of (R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-phenylethylamine 
were added to 8.5 g of toluene, and heated to 70.degree. C. so as to 
dissolve these reactants in the toluene. The reaction mixture was cooled 
to 20.degree. C. over 4 hours, and then kept standing at this temperature 
over night. 
The material, which had crystalline out, was separated by filtration. The 
amount of the crystalline material thus obtained was 1.47 g (yield: 
31.3%). The crystalline material was decomposed with a 1% hydrochloric 
acid, and then an extraction operation was carried out twice with 20 ml of 
toluene. The organic layer was concentrated under reduced pressure to give 
0.66 g of (S)-(+)-2-(4-chlorophenyl)isovaleric acid. 
Yield: 31%. 
The ratio of the optical isomers: 95.3% of (S)-(+)-isomer, and 4.7% of 
(R)-(-)-isomer. 
EXAMPLE 49 
2.09 g (0.01 mole) of (.+-.)-cis-permethric acid and 2.27 g (0.01 mole) of 
(R)-(+)-N-(p-hydroxybenzyl)-1-phenylethylamine were added to 1.5 g of 
isopropanol, and heated to 70.degree. C. so as to dissolve these reactants 
in the isopropanol. The reaction mixture was cooled to 20.degree. C. over 
4 hours, and then kept standing at this temperature over night. 
The material, which has crystallized out, was separated by filtration. The 
amount of the crystalline material thus obtained was 1.76 g (yield: 
40.3%). The crystalline material was decomposed with a 1% hydrochloric 
acid, and then an extraction operation was carried out twice with 20 ml of 
toluene. The organic layer was concentrated under reduced pressure to give 
0.84 g of (+)-cis-permethric acid. Yield: 40.2%. 
The ratio of the optical isomers: 98.8% of (+)-cis-isomer, and 1.2% of 
(-)-cis-isomer. 
EXAMPLE 50 
2.53 g (0.01 mole) of (.+-.)-ketoprofen and 2.27 g (0.01 mole) of 
(S)-(-)-N-(p-hydroxybenzyl)-1-phenylethylamine were added to 9.1 g of 
methanol, and heated to 60.degree. C. so as to dissolve these reactants in 
the methanol. The reaction mixture was cooled to 20.degree. C. over 4 
hours, and then kept standing at this temperature over night. 
The material, which had crystallized out, was separated by filtration. The 
amount of the crystalline material thus obtained was 2.09 g (yield: 
43.5%). The crystalline material was decomposed with a 1% hydrochloric 
acid, and then an extraction operation was carried out twice with 20 ml of 
toluene. The organic layer was concentrated under reduced pressure to give 
1.09 g of (+)-ketoprofen. Yield: 43.1%. 
The specific rotation of this substance [.alpha.].sub.D.sup.21 : 
+31.7.degree. (C 1.0, chloroform). The ratio of optical isomers: 79.1% of 
(S)-(+)-isomer, and 20.9% of (R)-(-)-isomer. 
EXAMPLE 51 
In this experiment, use was made of the chrysanthemic acid shown in Example 
33. A solution of 16 g (0.0952 mole) of the chrysanthemic acid in 15.5 g 
of toluene was added at 65.degree. C. under stirring to a solution of 
24.47 g (0.0951 mole) of 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-phenylethylamine in 24.5 g of 
toluene. Thereafter, a cooling operation was started for the reaction 
mixture. 5 mg of an 
(R)-(+)-N-(2-hydroxy-3-methoxybenzyl)-1-phenylethylamine salt of 
(+)-trans-chrysanthemic acid were added to the reaction mixture under 
cooling. 
After a material had crystallized out, the reaction mixture was kept at 
58.degree. C. for 1 hour, cooled to 20.degree. C. over 4 hours, and 
stirred at the latter temperature for 30 minutes. 
The crystalline material was separated out by filtration, washed twice with 
7 g of toluene, and decomposed with a 1% hydrochloric acid. Then, an 
extraction operation was carried out twice with 50 g of toluene. The 
organic layer was concentrated under reduced pressure to give 6.34 g of 
(+)-trans-chrysanthemic acid. Yield: 39.6%. Yield (D/D): 76.2%. The ratio 
of optical isomers: 0.5% of (+)-cis-isomer, 0.2% of (-)-cis-isomer, 95.7% 
of (+)-trans-isomer, and 3.7% of (-)-trans-isomer. 
EXAMPLE 52 
The procedures shown in Example 33 were repeated, except that 2.27 g (0.01 
mole) of (R)-(+)-N-(p-hydroxybenzyl)-1-phenylethylamine were used instead 
of (R)-(-)-N-(p-hydroxybenzyl)-1-(1-naphthyl)ethylamine, and that 33.6 g 
of toluene were employed instead of isopropanol. 
0.55 g of (+)-trans-chrysanthemic acid was obtained. Yield: 32.7%. Yield 
(D/D): 64.8%. The ratio of optical isomers: 0.6% of (+)-cis-isomer, 0% of 
(-)-cis-isomer, 98.3% of (+)-trans-isomer, and 1.1% of (-)-trans-isomer. 
COMATIVE EXAMPLE 1 
The procedures shown in Example 52 were repeated, except that 1.21 g (0.01 
mole) of (R)-(+)-.alpha.-phenylethylamine were used instead of 
(R)-(+)-N-(p-hydroxybenzyl)-1-phenylethylamine, and that 16 g of toluene 
were employed. 
1.23 g of chrysanthemic acid were obtained. Yield: 73.2%. Yield (D/D): 
59.9%. The ratio of the optical isomers: 0.3% of (+)-cis-isomer, 0.4% of 
(-)-cis-isomer, 40.6% of (+)-trans-isomer, and 53.3% of (-)-trans-isomer. 
COMATIVE EXAMPLE 2 
The procedures shown in Example 52 were repeated, except that 2.27 g (0.01 
mole) of (R)-(+)-N-(o-hydroxybenzyl)-1-phenylethylamine were used instead 
of (R)-(+)-N-(p-hydroxybenzyl)-1-phenylethylamine, and that 5 g of toluene 
were employed. 
There were no materials crystallized out. 
COMATIVE EXAMPLE 3 
The procedures shown in Example 52 were repeated, except that 2.77 g (0.01 
mole) of (R)-(+)-N-(o-hydroxybenzyl)-1-naphthylethylamine were used 
instead of (R)-(+)-N-(p-hydroxybenzyl)-1-phenylethylamine, and that 5 g of 
toluene was employed. 
There were no materials crystallized out. 
COMATIVE EXAMPLE 4 
The procedures shown in Example 44 were repeated, except that 2.11 g (0.01 
mole) of (S)-(+)-.alpha.-phenyl-.beta.-p-tolylethylamine were used instead 
of (R)-(+)-N-(p-hydroxybenzyl)-.alpha.-phenyl-.beta.-p-tolylethylamine, 
and that 21.8 g of toluene were employed. 
1.18 g of (+)-trans-chrysanthemic acid were obtained. Yield: 70.2%. Yield 
(D/D): 74.4%. The ratio of optical isomers: 1.7% of (+)-cis-isomer, 1.5% 
of (-)-cis-isomer, 52.0% of (+)-trans-isomer, and 44.8% of 
(-)-trans-isomer. 
COMATIVE EXAMPLE 5 
The procedures shown in Example 44 were repeated, except that 0.95 g (0.045 
mole) of (S)-(+)-.alpha.-phenyl-.beta.-p-tolylethylamine was used instead 
of (R)-(+)-N-p-hydroxybenzyl-.alpha.-phenyl-.beta.-p-tolylethylamine, and 
that 5.9 g of toluene were employed. 
0.42 g of (+)-trans-chrysanthemic acid was obtained. Yield: 25%. Yield 
(D/D): 47.4%. The ratio of optical isomers: 2.3% of (+)-cis-isomer, 0% of 
(-)-cis-isomer, 92.5% of (+)-trans-isomer, and 5.2% of (-)-trans-isomer. 
EXAMPLE 53 
1.52 g (0.01 mole) of (.+-.)-mandelic acid and 2.57 g (0.01 mole) of 
(S)-(-)-N-(2-hydroxy-3-methoxybenzyl)-1-phenylethylamine were added to 
6.84 g of toluene, and heated to 70.degree. C. so as to dissolve these 
reactants in the toluene. The reaction mixture was cooled to 20.degree. C. 
over 4 hours, and kept standing at this temperature over night. 
The material, which had crystallized out, was separated off by filtration. 
The amount of the crystalline material thus obtained was 1.64 g (yield: 
40.1%). 
The crystalline material was decomposed with a 1% hydrochloric acid, and an 
extraction operation was carried out twice with 20 ml of diethyl ether. 
The organic layer was concentrated under reduced pressure to give 0.59 g 
of (-)-mandelic acid. Yield: 38.8%. [.alpha.].sub.D.sup.20 : 
-152.8.degree. (C 2.8, H.sub.2 O) The ratio of optical isomers: 1.4% of 
(+)-isomers, and 98.6% of (-)-isomer.