Synthesis of 5-decenyl acetate and other pheromone components

Details Synthesis of 5-decenyl acetate and other pheromone components Synthesis of 5-decenyl acetate and other pheromone components

1999-09-01

2001-04-10

Killos, Paul J. (Department: 1623)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

C560S261000

Reexamination Certificate

active

06215019

ABSTRACT:

TECHNICAL FIELD
The present invention relates to synthetic pheromones and, in particular, to an improved synthesis of E-5-decenyl acetate, the major component of the Peach Twig Borer pheromone (PTB pheromone).
BACKGROUND OF THE INVENTION
The Peach Twig Borer (PTB) is a major pest in stone fruit orchards. One pest control method currently employed involves spraying orchards with insecticides. This method is problematic in various ways. Insecticides are applied directly to the fruit, a practice that is contrary to an increasing preference for organic produce as well as contrary to water quality issues and other environmental concerns. Insecticides are also nondiscriminate killers and kill beneficial insects as well as harmful insects. Finally, the PTB is becoming resistant to many of the common insecticides.
An alternative method to control insect populations involves the use of the insect's sex attractant to confuse the male insect and thereby prevent mating and eliminate future insect generations. This technique is called mating pattern disruption. The biggest problem in using mating pattern disruption to control insect populations is the cost of producing the insect pheromone. Usually the cost of insect pheromone application is the same as or greater than traditional insecticide applications. Methods that reduce the production costs of insect pheromones would make mating pattern disruption an economical technique for controlling insect populations.
PTB pheromone is an 85:15 ratio of E-5-decenyl acetate and E-5-decenol. Thus production of 5-decenyl acetate, which is the major component of PTB pheromone, is a significant step of the PTB pheromone manufacturing process. The acetate can be subsequently removed by hydrolysis to obtain E-5-decenol, the other component of PTB pheromone.
A fast, inexpensive, and high yield process for synthesizing E-5-decenyl acetate is, therefore, desirable.
SUMMARY OF THE INVENTION
An object of the invention is, therefore, to improve the process for manufacturing PTB pheromone.
FIGS. 1A
,
1
B,
1
C, and
1
D (collectively
FIG. 1
) depict a recent method of producing 5-decenyl acetate disclosed in U.S. Pat. No. 5,916,983 of Pederson and Grubbs. The synthesis produces 1-chlorohexene by coupling allyl magnesium chloride and bromochloropropane. A 40 percent yield of a 60:40 isomeric ratio of trans:cis 1-chloro-5-decene is then obtained by olefin metathesis of 1-chlorohexene and 1-hexene. The metathesis catalyst used in this process is bis(tricyclohexylphosphine)dichloro ruthenium (II) benzylidene [(PCy
3
)
2
Cl
2
]Ru═CBPh, referred to as “Grubbs' catalyst.” These reactions were performed between 32° C. and 62° C., because at room temperature, the reaction is slow and conversions are lower. A 27 percent yield was obtained when the reaction was run at 32°. 1-Chloro-5-decene is converted to 5-decenyl acetate by heating the former with potassium acetate in acetic acid. The resulting 60:40 ratio of trans:cis 5-decenyl acetate is isomerized to an 80:20 ratio of trans:cis 5-decenyl acetate by the sodium salt of benzenesulfinic acid in acetic acid.
The low 25 to 27 percent gross yield of 5-decenyl acetate is largely due to the formation of a methylidene ruthenium catalyst intermediate, which is a thermodynamically stable alkylidene that prevents high conversion of starting materials to products and prevents the formation of a high trans isomeric product.
This method typically required 18 to 25 days to produce 12 Kg of 5-decenyl acetate in an 80:20 cis:trans ratio using standard-sized equipment (multiple reactions needed to be run because of low yields and many of the reactions needed to be diluted with solvents to work properly). In particular, five days were required to run the reaction and to work up and distill the l-chloro-5-decene. Three metathesis runs at one day each, plus two days to remove the catalyst, and 2 days to distill, were needed to produce the 1-chloro-5-decene for a subtotal of seven days. The subsequent production of 5-decenyl acetate with a trans:cis ratio of 60:40 required two to three runs at 36 to 48 hours each to achieve 98 percent conversion, for a subtotal of four to six days. Twenty-four hours for each of two batches were required to achieve the isomerization of 5-decenyl acetate to an 80:20 ratio of trans:cis, for a subtotal of two days. The total time of 18 to 25 days does not include the time for the final distillation.
Although the 20 percent cis-5-decenyl acetate does not affect the efficacy of the PTB pheromone in lures and mating disruption applications, the low yield and the long completion time make the process expensive. In view of the numerous reaction steps, the large amount of required starting materials and reagents, the long reaction times, and/or the overall low yield, this manufacturing process for 5-decenyl acetate is still not satisfactory.
The invention provides, therefore, an improved synthesis of E-5-decenyl acetate that eliminates many of the problems associated with the previous method. The improved synthesis employs fewer reaction steps, uses stable and readily available starting materials, has a shorter reaction time, and provides a good product yield without the need for expensive and sophisticated equipment. In a preferred embodiment, the improvements include: 1) a technique to obtain higher conversion of starting materials to products (from 40 percent to greater than 75 percent); 2) an increase in the metathesis trans:cis ratio from 60:40 to between 80:20 to 84:16; 3) only two reaction steps; and 4) a production time of less than a week.
In the preferred embodiment, certain of these improvements are accomplished by self-metathesizing 1-hexene to 5-decene followed by cross-metathesizing of 5-decene and 5-hexenyl acetate. The self-metathesis of 1-hexene is performed in the presence of Grubbs' catalyst [(PCy
3
)
2
Cl
2
]Ru═CHPh. Further, the ethylene side product is allowed to bubble out of solution. The 5-decene produced by the self-metathesis is cross-metathesized with 5-hexenyl acetate to yield greater than 98 percent pure 5-decenyl acetate with an 80:20 to 84:16 trans:cis ratio. The reaction is performed in the presence of Grubbs' catalyst and under vacuum in order that the side product 1-hexene is removed from solution. The elimination of 1-hexene prevents the formation of the methylidene catalyst intermediate and leads to an increased yield and a more desirable trans isomeric product ratio (86:14 as compared to the earlier 60:40).
In a more general embodiment, the invention provides a method for synthesizing olefinic alcohols, acetates, aldehydes, carboxylic acids or derivatives thereof by self-metathesizing a first alpha olefin in an exemplary form of CH
2
CH(CH
2
)
n
(CHX)(CH
2
)
m
CH
3
, where X is selected from a hydrogen, alcohol, acetate, halide, tosylate, or mesylate or derivative thereof, and n and m are each selected from zero and an integer less than or equal to 20, in the presence of a first catalyst to form a product in the form of CH
2
CH(CH
2
)
p
(CHX)(CH
2
)
q
CH
3
, where p and q are each selected from zero and an integer such that at least p is greater than n or at least q is greater than m and a first side product in the form of CH
2
Y, where Y is selected from CH
2
or CH(CH
2
)
n
(CHX)(CH
2
)
m
CH
3
; and then cross-metathesizing the product with a second alpha olefin in an exemplary form of NCH(CH
2
)
r
M, where N is selected from CH
2
or CH(CH
2
)
r
M, r is selected from zero and an integer less than or equal to 20, and M is selected from an alcohol, acetate, aldehyde, halide, carboxylic acid, or derivative thereof in the presence of a second catalyst to form CH
3
(CH
2
)
m
(CHX)(CH
2
)
n
CHCH(CH
2
)
r
M or derivatives thereof and a second side product in the form of CH
2
Z, where Z is selected from CH
2
or CH(CH
2
)
n
(CHX)(CH
2
)
m
CH
3
under conditions of sufficiently high temperature and/or sufficiently low pressure (vacuum) such that the second side product evaporates out of the reaction mixture.
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