Method for the isomerization of cis-alkenyl compounds

An object of the present invention is to provide a method for the preparation of geometrical isomers which are important as constituents of synthetic pheromones, synthetic perfumes, terpenes and the like (i.e., a method for the isomerization of cis-alkenyl compounds to their trans-isomers). In this method, the above-described object is accomplished by reacting a cis-alkenyl compound in the presence of nitric acid used as the sole catalyst.

FIELD OF THE INVENTION AND RELATED ART STATEMENT 
This invention relates to a method for the preparation of geometrical 
isomers which are important as constituents of synthetic pheromones, 
synthetic perfumes, terpenes and the like. More particularly, it relates 
to a method for the isomerization of cis-alkenyl compounds to their 
trans-isomers. 
In recent years, the technique of utilizing synthetic sex pheromones to 
predict the breeding of harmful insects or disturb communications between 
harmful insects has made great progress for the main purpose of 
controlling harmful insects of the order Lepidoptera. Thus, the 
utilization of synthetic sex pheromones is now in the stage of practical 
application. 
Sex pheromones produced by lepidoptera are composed chiefly of unsaturated 
aliphatic compounds, and most of them are alkenes and alkadienyl 
compounds. Moreover, the position of an unsaturated bond or bonds in these 
components, their geometrical structure (i.e., cis- or trans-form), and 
the mixing ratio of these components have already been determined. The 
results thus obtained constitute an important factor to be considered in 
the synthesis of sex pheromones. 
Conventionally known techniques for the isomerization of cis-isomers to 
trans-isomers are as follows: 
An isomerization reaction using a mercapto-containing compound or a 
disulfide as a catalyst is described in Japanese Patent Publication Nos. 
57608/'87 and 58337/'87. 
Moreover, an isomerization reaction using elemental selenium (Se) as a 
catalyst is described in Journal of Am. Oil Chem. Soc., 26, 83, 1949. 
Furthermore, an isomerization reaction using a mineral acid (e.g., nitrous 
acid, sulfurous acid or the like) as a catalyst and conducted in an 
organic solvent is described in Journal of Am. Oil Chem. Soc., 26, 83, 
1949. 
In addition, an isomerization method using nitrous acid derived from sodium 
nitrite and a mineral acid as a catalyst is described in the Journal of 
the Japanese Society of Chemical Synthesis, 38(7), 643-646, 1987. 
However, these conventional techniques have the following respective 
disadvantages. 
In the isomerization reaction using a mercapto-containing compound or a 
disulfide as a catalyst, the mercapto-containing compound used as a 
catalyst imparts an unpleasant mercapto odor to the products. This is 
especially undesirable in the case of perfume products having fragrance 
for their commercial value. 
In the isomerization reaction using elemental selenium (Se) as a catalyst, 
selenium (Se) falls under the class of poisons as provided for according 
to the Poisonous and Deleterious Substances Control Law in Japan and is 
undesirable from the viewpoint of safety, hygiene and environmental 
protection. 
The isomerization reaction using a mineral acid (e.g., nitrous acid, 
sulfurous acid or the like) as a catalyst and conducted in an organic 
solvent is undesirable in that it involves a high cost and requires a 
complicated procedure owing to the necessity of recovering the organic 
solvent. Moreover, mineral acids exhibit a powerful isomerizing activity, 
but have the disadvantage that they tend to cause polymerization and/or a 
shift of the double bond in olefinic compounds, resulting in a reduction 
in yield and purity. In particular, a shift of the double bond may cause a 
subtle change of odor in perfumes, and may produce impurities exerting a 
serious influence on biological activities in sex pheromones. Accordingly, 
it is very important to minimize the shifts of the double bonds. 
The isomerization reaction using nitrous acid derived from sodium nitrite 
and a mineral acid as a catalyst is also undesirable in that it involves a 
high cost and the use of a mineral acid produces the same disadvantage as 
described above. 
Thus, conventional isomerization techniques have their respective 
disadvantages and there has been a demand for the development of a new 
technique. 
In view of these circumstances, it is an object of the present invention to 
provide a method for the isomerization of cis-alkenyl compounds to their 
trans-isomers with a high degree of isomerization and a high selectivity. 
SUMMARY OF THE INVENTION 
The present inventors made an intensive investigation for the purpose of 
solving the above-described problem. As a result, it has unexpectedly been 
found that, by adding 0.5 to 3% by weight of nitric acid (as expressed in 
terms of pure HNO.sub.3) to cis-alkenyl compounds and reacting them at 
temperature of 60.degree. to 150.degree. C. for a period of 0.5 to 5 
hours, their trans-isomers can be obtained at a degree of isomerization of 
50 to 81% and a selectivity of 99 to 100%. Although 61% nitric acid was 
used in the examples given below, 65%, 70% and 98% products are also 
commercially available. Any of these products may be used in the present 
invention without difficulty. 
As used herein, the term "degree of isomerization" means the percentage of 
the trans-isomer in the reaction product (i.e., the resulting mixture of 
cis- and trans-isomers). The term "selectivity" means the ratio of the 
purity of the reaction product (i.e., the resulting mixture of cis- and 
trans-isomers) to that of the starting material, and indicates the degree 
of reduction in purity due to side reactions such as a shift of the double 
bond during isomerization reaction. 
As described above, the use of nitric acid as the sole catalyst makes it 
possible to isomerize cis-alkenyl compounds to their trans-isomers with a 
high degree of isomerization and a high selectivity. Moreover, this can 
overcome the disadvantages possessed by conventional techniques, such as 
safety problems and high cost. 
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
Several isomerization methods were compared with respect to cis-3-heptenol. 
The results thus obtained are summarized in Table 1 below. 
TABLE 1 
__________________________________________________________________________ 
Isomeriza- 
2-Mercap- 
Selenium 
HCl + NaNO.sub.2 + 
Nitric 
tion method 
toethanol 
(Se) isopro- 
HCl acid (as 
(catalyst panol pure 
and other HNO.sub.3) 
factor) 
Reaction 
Starting 
Same as 
Same as 
Same as 
Same as 
conditions 
material, 
left left left left 
300 g (2.6 
moles) 
2-Mercap- 
Se, 3 g 
HCl, 15 g 
NaNO.sub.2, 9 g 
HNO.sub.3, 2 g 
toethanol, Isopro- 
Aqueous 
9 g panol, 
HCl, 24 g 
600 g 
Stirred at 
Stirred at 
Stirred at 
Stirred at 
Stirred at 
90-100.degree. C. 
170-180.degree. C. 
80-90.degree. C. 
80-90.degree. C. 
80-90.degree. C. 
for 4 for 3 for 3 for 3 for 3 
hours hours hours hours hours 
Degree of 
58 62 52 66 77 
isomeriza- 
tion (%) 
Selectivi- 
93 94 90 94 99 
ty (%) 
__________________________________________________________________________ 
It can be seen from Table 1 that the isomerization method using nitric acid 
as a catalyst in accordance with the present invention is superior to the 
other methods in degree of isomerization and selectivity. 
When nitric acid is used as the sole catalyst, the amount of catalyst added 
is generally in the range of 0.5 to 3% by weight (as expressed in terms of 
pure HNO.sub.3), though it depends on the isomerizing tendency of the 
cis-alkenyl compound. For cis-alkenyl compounds having a relatively low 
molecular weight, it will suffice to add nitric acid in an amount of 0.5 
to 1.5% by weight (as expressed in terms of pure HNO.sub.3) based on the 
weight the cis-alkenyl compound. In some cases, the reaction may be 
conducted in the presence of toluene, xylene, n-hexane or the like. 
The isomerization reaction is generally conducted at a temperature in the 
range of 80.degree. to 100.degree. C., though it depends on the structure 
of the cis-alkenyl compound. If the temperature is lower than 60.degree. 
C., the degree of isomerization will be reduced to 5-10%, while if the 
temperature is unduly high, the selectivity will tend to lower.

Specific examples of cis-alkenyl compounds to which the method of the 
present invention can be applied include alkenes such as cis-3-hexene, 
cis-3-heptene and cis-3-decene; alkenols such as cis-3-hexenol, 
cis-3-heptenol, cis-3-octenol and cis-6-nonenol; alkenyl esters such as 
methyl oleate, cis-8-dodecenyl acetate and cis-3-hexenyl acetate; alkenyl 
halides such as cis-3-hexenyl chloride, cis-3-heptenyl chloride, 
cis-3-octenyl chloride and cis-3-decenyl chloride; and alkenoic acids such 
as oleic acid and cis-5-tetradecenoic acid. However, it is to be 
understood that the present invention is not limited thereto. 
EXAMPLE 1 
(Isomerization of cis-4-tridecenyl chloride with the aid of nitric acid) 
500 g (2.3 moles) of cis-4-tridecenyl chloride and 7.5 g of nitric acid (as 
expressed in terms of pure HNO.sub.3) were placed in a 2-liter reactor and 
stirred at 80.degree.-85.degree. C. for 3 hours. Thereafter, the mixture 
was washed with 500 g of a 5% aqueous solution of sodium hydroxide and 
then twice with 500-g portions of purified water. 
The resulting substance was distilled to obtain 495 g of an oily liquid 
(with a vapor pressure of 2-3 mmHg at 130.degree. C.). Then, this product 
was examined for degree of isomerization and selectivity by gas 
chromatography. 
Thus, a mixture of trans-4-tridecenyl chloride and cis-4-tridecenyl 
chloride was obtained at a degree of isomerization of 78% and a 
selectivity of 99%. 
EXAMPLES 2-6 
Attempts were made to isomerize other cis-alkenyl compounds in the same 
manner as in Example 1. The starting materials and reaction conditions 
employed are shown in Tables 2 and 3 below. Comparative Example 1 
(Isomerization of cis-4-tridecenyl chloride with the aid of 
2-mercaptoethanol) 
500 g (2.3 moles) of cis-4-tridecenyl chloride, which was used for reaction 
in Example 1, was placed in a 2-liter reactor, and 25 g (0.32 mole) of 
2-mercaptoethanol was added thereto. This mixture was stirred at 
90.degree.-95.degree. C. for 3 hours. Then, the isomerization reaction was 
stopped by cooling the mixture to room temperature. Thereafter, the 
mixture was subjected to after-treatments as described in Example 1. 
Thus, a mixture of trans-4-tridecenyl chloride and cis-4-tridecenyl 
chloride was obtained at a degree of isomerization of 62% and a 
selectivity of 93%. 
Comparative Example 2 
(Isomerization of cis-8-dodecenyl acetate with the aid of NaNO.sub.2 and 
HCl) 
500 g (2.2 moles) of cis-8-dodecenyl acetate, 15 g of NANO.sub.2, and 40 g 
of a 20% aqueous solution of HCl were placed in a 2-liter reactor and 
stirred at 80.degree.-90.degree. C. for 3 hours. Then, the isomerization 
reaction was stopped by cooling the mixture to room temperature. 
Thereafter, the mixture was subjected to after-treatments as described in 
Example 1. 
Thus, a mixture of trans-8-dodecenyl acetate and cis-8-dodecenyl acetate 
was obtained at a degree of isomerization of 65% and a selectivity of 93%. 
The above-described results are summarized in Tables 2 and 3 below. 
TABLE 2 
______________________________________ 
Example 
Example Example Example 
1 2 3 4 
______________________________________ 
cis-Alkenyl com- 
cis-4-Tri 
cis-3- cis-3- cis-3- 
pound decenyl Hexene Heptenol 
Octenyl 
chloride chloride 
Weight percentage 
1.5 1.0 1.0 1.0 
of nitric acid 
(as pure HNO.sub.3) 
based on starting 
material 
Reaction tempera- 
80-85 60-65 80-85 85-90 
ture (.degree.C.) 
Reaction time 
3.0 3.0 3.0 3.0 
(hrs) 
Degree of iso- 
78 70 74 81 
merization (%) 
Selectivity (%) 
99 100 99 99 
______________________________________ 
TABLE 3 
______________________________________ 
Compar- 
ative Compara- 
Example 
Example Example tive 
5 6 1 Example 2 
______________________________________ 
cis-Alkenyl com- 
Oleic cis-8- cis-4-Tri- 
cis-8- 
pound acid Dode- decenyl 
Dodecenyl 
cenyl chloride 
acetate 
acetate 
Weight percentage 
1.5 1.5 -- -- 
of nitric acid 
(as pure HNO.sub.3) 
based on starting 
material 
Reaction tempera- 
85-90 90-95 90-95 80-90 
ture (.degree.C.) 
Reaction time 
3.0 3.0 3.0 3.0 
(hrs) 
Degree of iso- 
78 80 62 65 
merization (%) 
Selectivity (%) 
99 99 93 93 
______________________________________ 
Application Example 1 
(Synthesis of trans-4-tridecenyl acetate) 
495 g (2.2 moles) of the mixture of trans-4-tridecenyl chloride and 
cis-4-tridecenyl chloride synthesized in Example 1, 432 g (4.4 moles) of 
potassium acetate, and 264 g (4.4 moles) of acetic acid were mixed under 
an atmosphere of nitrogen (N.sub.2) and stirred at 180.degree.-185.degree. 
C. for 10 hours. Thereafter, this mixture was washed with 600 g of 
purified water and then with 600 g of a 5% aqueous solution of sodium 
bicarbonate. The resulting organic layer was purified by distillation. 
Thus, there was obtained 548 g (2.2 mole) of 4-tridecenyl acetate having a 
trans to cis ratio of 78:22 and a purity of 98%. This product is a sex 
pheromone component of the tomato pinworm (Keiferia lycopersicella) known 
as an insect pest of tomato fields principally in the United States of 
America.