The present invention relates to a method for producing an optically active (+)-(s)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone which comprises reacting (.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate of the formula (II), ##STR1## with an optically active (+)-.alpha.-phenyl-.beta.-p-tolylethylamine to produce diastereomer salts, separating an optically active (-)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate by making use of a solubility difference between the diastereomer salts, and then hydrolyzing said optically active acid phthalate in water or a solvent containing water in the presence or absence of a base below the small excess of the stoichiometric amount, and novel (.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate and its production.

The present invention relates to a method for producing an optically active 
(+)-(s)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone of the formula 
(I), 
##STR2## 
More particularly, it relates to a method for producing an optically active 
(+)-(s)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone of the formula 
(I) which comprises reacting 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate of 
the formula (II), 
##STR3## 
with an optically active (+)-.alpha.-phenyl-.beta.-p-tolylethylamine to 
produce diastereomer salts, separating an optically active 
(-)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate by 
making use of a solubility difference between the diastereomer salts, and 
then hydrolyzing said optically active acid phthalate in water or a 
solvent containing water in the presence or absence of a base below the 
small excess of the stoichiometric amount. 
Further, the present invention relates to novel 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate of 
the formula (II) and its production. More particularly, it relates to a 
method for producing 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate of 
the formula (II) which comprises reacting 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone with phthalic 
acid in the presence of a base. 
Allethrin of the formula (III), 
##STR4## 
known as typical agricultural chemicals having the skeleton of 
cyclopentenolone was invented by M. S. Schechter in 1949, and it has 
widely been used in the world because of its excellent insecticidal 
activity and low toxicity. As to a method for synthesizing the alcohol 
moiety of allethrin, i.e. allethrolone of the formula (IV), 
##STR5## 
there are many well-known ones including synthetic methods for the optical 
isomers of allethrolone. 
While it is well known that esters resulting from cyclopentenolone of the 
formula (I) having a similar structure to allethrolone and various acids 
have also a strong insecticidal activity like allethrin, and particularly 
that the compound of the formula (V), 
##STR6## 
which is an ester resulting from cyclopentenolone and 
2,2,3,3-tetramethylcyclopropanecarboxylic acid, has extremely strong 
knock-down and lethal effects (Published Examined Japanese Patent 
Application No. 15843/1975). 
Further, the alcohol of the formula (I) has an asymmetric carbon atom at 
the 4-position so that it exists as two optical isomers. And, an ester 
resulting from one of the isomers, an optically active 
(+)-(s)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone, and 
2,2,3,3-tetramethylcyclopropanecarboxylic acid, has an insecticidal 
activity of about 2 times as strong as that of its racemate. 
As a result of the inventors' extensive study over a long period of time, 
the inventors succeeded in synthesizing an optically active 
4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate. Further, 
the inventors developed a method for producing an optically active 
(+)-(s)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone, an unknown 
compound before the present invention, by hydrolyzing the optically active 
acid phthalate in water or a solvent containing water with a base of a 
small excess over the theoretical equivalent. 
And, the inventors developed a method for producing novel 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate, 
which is the starting material of the above process. 
The method of the present invention is carried out as follows: Firstly, the 
(.+-.)-.alpha.-phenyl-.beta.-p-tolylethylamine salt of 
(-)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate is 
obtained by reacting 1 mole of 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate 
which may optionally contain in part an optically active 
4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate with 0.5 
to 1.0 mole of an optically active 
(+)-.alpha.-phenyl-.beta.-p-tolylethylamine in an inert solvent, 
collecting the precipitated crystalline salt by filtration and if 
necessary recrystallizing the salt from a suitable solvent. Then, the 
objective optically active 
(+)-(s)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone is obtained by 
decomposing the salt as usual with an acid or alkali to obtain 
(-)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate and 
hydrolyzing the acid phthalate in water or a solvent containing water with 
a base below the small excess of the theoretical equivalent. 
Referring to the present invention in more detail, 1 mole of 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate 
which may optionally contain in part an optically active 
4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate is 
allowed to react with 0.5 to 1.0 mole of an optically active 
(+)-.alpha.-phenyl-.beta.-p-tolylethylamine in an inert solvent (e.g. 
aromatic hydrocarbon solvents such as benzene and toluene; ether solvents 
such as diethyl ether and diisopropyl ether; aliphatic hydrocarbon 
solvents such as n-hexane, n-pentane and n-heptane; mixtures of these 
solvents in suitable proportions). 
The reaction is effected usually at temperature of -10.degree. C. to the 
boiling point of the used solvent and comes to an end in 10 minutes to 48 
hours. The precipitated crystalline salt is collected by filtration and if 
necessary recrystallized from a suitable solvent (e.g. aromatic 
hydrocarbon solvents such as benzene and toluene; ether solvents such as 
diethyl ether and diisopropyl ether; aliphatic hydrocarbon solvents such 
as n-hexane, n-pentane and n-heptane; alcohol solvents such as isopropyl 
alcohol, ethyl alcohol and tert-butyl alcohol; mixtures of these solvents 
in suitable proportions) to obtain the 
(+)-.alpha.-phenyl-.beta.-p-tolylethylamine salt of 
(-)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate. This 
salt is then decomposed as usual with an acid or alkali to obtain 
(-)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate. 
Examples of the used acid includes diluted hydrochloric acid and diluted 
sulfuric acid, and examples of the used alkali are the aqueous solution of 
hydroxides of an alkali metal (e.g. sodium, potassium) and carbonates of 
an alkali metal (e.g. sodium, potassium). The (-)-acid phthalate is then 
decomposed at room temperature (10.degree. C.) to 200.degree. C. for 5 
minutes to 100 hours in water or a solvent containing water. In this case, 
the application of pressure, 1.5 to 10 atm., to the reaction system for 
rapid completion of the reaction, the addition of a base of a 0 to 1.5 
moles of the theoretical equivalent based on 
(-)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate and 
the addition of a pH buffer (e.g. an aqueous solution of sodium acetate, 
sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium hydrogen 
phosphate, potassium dihydrogen phosphate, etc.) give desirable effects in 
terms of the rate of reaction. The usable solvent includes for example 
water and water-soluble solvents (e.g. methanol, ethanol, glycerin, 
ethylene glycol, tetrahydrofuran, acetone, dioxane, dimethylformamide, 
dimethyl sulfoxide). Also, in order to protect 
(+)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone produced during the 
reaction, a solvent sparingly soluble in water (e.g. diethyl ether, 
benzene, toluene, chloroform, carbon tetrachloride, n-hexane, methyl ethyl 
ketone) may be added to the reaction system, or the reaction may be 
carried out in a buffer solution to keep the pH of the reaction system 
nearly neutral. The base used herein is not particularly limited, and it 
includes for example hydroxides and oxides of an alkali metal (e.g. 
sodium, potassium) or alkaline earth metal (e.g. calcium, barium), their 
salts with weak acids (e.g. carbonic acid, bicarbonic acid, boric acid, 
acetic acid), ammonia and organic amines. As the organic amines, any of 
primary, secondary and tertiary amines may be used. For example, there may 
be given ethylamine, triethylamine, cyclohexylamine, dicyclohexylamine, 
pyridine, pyrrolidine, piperidine, aniline, quinoline and picoline. The 
reaction solution thus obtained is then saturated with sodium chloride, 
followed by extraction. The organic layer separated is washed with a 
sodium chloride-saturated water, dried and concentrated under reduced 
pressure to obtain almost pure 
(+)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone. 
Next, there is provided a method for producing 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate of 
the formula (II). 
Firstly, (.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid 
phthalate is obtained by reacting 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone with phthalic 
anhydride in the presence of a base in an inert solvent, adding water in 
an amount of 0.5 to 3.0 times the volume of the reaction solution and 
separating the water layer, adding a small amount of 10% aqueous 
hydrochloric acid to the obtained water layer for neutralization, 
extracting with an organic solvent such as ethyl acetate, diethylether, 
etc., and removing the organic solvent by evaporation. The resulting oily 
product, (.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid 
phthalate is obtained. 
Referring to the present invention in more detail, the reaction is effected 
usually at a temperature of 0.degree. to the boiling point of the used 
solvent and comes to an end in 5 minutes to 10 hours.

The reaction may be carried out in an organic solvent (e.g. aromatic 
hydrocarbon solvents such as benzene and toluene; ether solvents such as 
diethyl ether and diisopropyl ether; dichloromethane. Examples of the base 
includes tertiary amines such as pyridine and triethylamine. The base is 
usually employed in an amount of 1.0 to 2.0 moles to 1 mole of 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone. Phthalic 
anhydride is usually employed in an amount of 1.0 to 1.5 moles to 1 mole 
of (.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone. The present 
invention will be illustrated in more detail with reference to the 
following examples. 
EXAMPLE 1 
(.+-.)-4-Hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate 
(8.9 g) was dissolved in diethyl ether (30 ml), and 
(+)-.alpha.-phenyl-.beta.-p-tolylethylamine (6.3 g) was added thereto, 
followed by stirring at room temperature for a whole day and night. The 
produced salt is collected by filtration and washed with diethyl ether to 
obtain 15.0 g of the salt as white crystals (m.p. 96.degree. C.). Benzene 
(150 ml) was added to this salt, and the mixture was heated to 70.degree. 
C. and allowed to cool with stirring for a whole day and night. The 
produced crystals were collected by filtration to obtain 6.3 g of a white 
crystal (m.p. 112.degree. C.). The crystal was then recrystallized from 
benzene (50 ml) to obtain 5.4 g of a white crystals (m.p. 112.degree. C.). 
The crystal was then recrystallized from benzene (50 ml) to obtain 5.4 g 
of a white crystal (m.p. 115.degree. C.). The crystal was then suspended 
in diethyl ether (90 ml), and a 1% aqueous hydrochloric acid (75 ml) was 
added, followed by stirring for 30 minutes. The ether layer was once 
washed with a 1% aqueous hydrochloric acid, and the solvent was removed by 
evaporation to obtain 2.7 g of 
(-)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate as an 
oily product. [.alpha.].sub.D.sup.22 =-21.5.degree. (c=0.53, CHCl.sub.3). 
This oily product was once dissolved in a mixture of water (18 ml) and 
sodium hydrogen carbonate (0.75 g), and then a 10% aqueous hydrochloric 
acid (2-3 cc) was added to the solution to adjust the pH to 5. The 
solution was refluxed with stirring for 8 hours. The reaction solution was 
cooled and extracted with addition of ethyl acetate, water and sodium 
chloride. After removing the solvent by evaporation, the resulting crude 
oily product was purified by passing it through a silica gel column using 
a 2:1 mixture of n-hexane and ethyl acetate as solvent. Thus, 1.1 g of 
(+)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone was obtained. 
[.alpha.].sub.D.sup.21 =+22.4.degree. (c=0.5, CHCl.sub.3), 
n.sub.D.sup.23.5 1.5275. By gas chromatography on an optically active 
column, it was found that the optical purity of this product was 100%. 
EXAMPLE 2 
(-)-4-Hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate was 
synthesized by the same manner as in the Example 1. [.alpha.].sub.D.sup.22 
=-21.5.degree. (c=0.53, CHCl.sub.3). The oily (-)-acid phthalate (2.7 g) 
was dissolved in water (25 ml) and the mixture was refluxed with stirring 
for 10 hours. The reaction mixture was worked up and purified in the same 
manner as in Example 1. Thus, 0.9 g of 
(+)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone was obtained. 
[.alpha.].sub.D.sup.20 =+21.8.degree. (c=0.4, CHCl.sub.3), n.sub.D.sup.20 
1.5270. 
EXAMPLE 3 
(-)-4-Hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate 
([.alpha.].sub.D.sup.22 =21.0.degree. (c=0.50, CHCl.sub.3)) (2.7 g) was 
dissolved in water (20 ml) solution of sodium acetate (0.5 g) and the 
resulting solution was refluxed with stirring for 15 hours. 0.85 Gram of 
(+)-4-hydroxy-3-methyl-2-2'-propynyl-cyclopentenone was obtained after the 
same purification as in Example 1. [.alpha.].sub.D.sup.20 =+20.8 (c=0.51, 
CHCl.sub.3). 
EXAMPLE 4 
(.+-.)-4-Hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone (7.50 g) and 
phthalic anhydride (7.40 g) were dissolved in toluene (50 ml). 
Triethylamine (6.0 g) was added to this solution over an hour. The 
resulting solution was stirred for 2 hours at 25.degree. C. Then water (50 
ml) was added to the mixture and the water layer was separated. 10% 
Hydrochloric acid (about 25 ml) was added to the water layer and this 
solution was twice extracted with diethyl ether (100 ml.times.2). The 
ether extract was washed with NaCl solution (50 ml) and dried over 
MgSO.sub.4. After removing the solvent, the almost pure 
(.+-.)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone acid phthalate 
(13.2 g) was obtained. Yield: 88.6%, n.sub.D.sup.25.5 1.5403. 
EXAMPLE 5 
The optically active 
(-)-(s)-2-methyl-3-2'-propynyl-cyclopent-2-en-4-on-1-yl 2,2,3,3-tetramethy 
lcyclopropanecarboxylate [.alpha..sub.D =-7.2.degree., c=(0.5, CHCl.sub.3)] 
[Compound A] is obtained by reacting the present compound, 
(+)-(s)-4-hydroxy-3-methyl-2-2'-propynyl-2-cyclopentenone with 
2,2,3,3-tetramethylcyclopropanecarbonyl chloride in the manner described 
in U.S. Pat. No. 3,876,681. 
And, the Compound A and reference compound were dissolved in kerosene to 
obtain an oil spray having the prescribed concentration of each compound. 
Ten northern house mosquito female adults (Culex pipiens pallens) and ten 
housefly adults (Musca domestica) were liberated in a (70 cm).sup.3 glass 
chamber, and 0.7 ml of the above oil spray was sprayed into the chamber. 
Thereafter, the number of knocked-down insects was counted with the lapse 
of time, and the value of KT.sub.50 was obtained from the average 
knock-down ratio of three replications according to the Finney's method. 
______________________________________ 
KT.sub.50 (sec) 
Concen- Northern house 
Test tration Housefly mosquito female 
compound (%) adult adult 
______________________________________ 
Compound A 0.1 84 &lt;30 
0.05 130 38 
0.025 200 68 
Reference 0.1 120 44 
Compound* 0.05 210 85 
0.025 380 122 
______________________________________ 
*Compound described in U.S. Pat. No. 3876681.