Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus esters
Reexamination Certificate
2002-07-30
2004-07-20
Desai, Rita (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Phosphorus esters
Reexamination Certificate
active
06765107
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a new manufacturing method for phosphonate esters, which have utility as a carbon-carbon binding formation agent, as well as a synthesis intermediate for biologically active substances such as medical drugs and agri-chemicals.
It has been known that the basic skeleton of the phosphonate esters can be found in nature and by using enzymes, etc., it shows biological activity. For example, through an additive reaction to the carbonyl compounds, the Homer-Emmons reaction is efficiently achieved, and therefore it has been widely used as a synthesizing method for various olefins, and as a synthesizing method for polyenes, which are often found in natural substances for the case of allylphosphonate esters. Therefore, phosphonate esters are effective as carbon-carbon binding formation reagents, and in particular they are compounds that are effective as the synthetic intermediate for medical drugs and agri-chemicals.
BACKGROUND ART
As a method of synthesizing phosphonate esters along with the formation of a carbon-phosphorus bond, in general, the method in which the corresponding halide is substituted with trialkylphosphite has been known. However, with this method, different types of halide compounds are formed along with the reaction and a large volume of by-products are generated. In addition, halides newly generated through the reaction additionally react with the trialkylphophite, so that a disadvantage is that a large volume of sub-products is created. Therefore, the method of the prior art cannot be said to be an industrially advantageous method.
DISCLOSURE OF THE INVENTION
The present invention was created by taking the above-mentioned circumstances into account and its objective is to provide an industrially advantageous manufacturing method for phosphonate esters in which the phosphonate esters of the subject can be obtained with a high yield through a simple operation with a minimum of side reaction or sub-products.
In order to avoid the above-mentioned issues, the present invention was conducted after a diligent study of the reaction of secondary phosphonate esters and alkenes that are easy to obtain, and consequently, it was found that the addition reaction advances in the presence of various transition metal catalysts, and phosphonate esters can be obtained with a high yield, thereby achieving the present invention.
In addition, as a result of a diligent study of the reaction of secondary cyclic phosphonate esters and dienes, which are easy to obtain, it was found that the addition reaction advances in the presence of various palladium catalysts, and the new allylphosphonate esters have a high yield and the present invention was completed.
In other words, the present invention has characteristics such that in the presence of a transition metal catalyst, an alkene compound expressed by the general formula (I):
R
1
R
2
C═CR
3
R
4
(I)
(In the formula, each of R
1
to R
4
individually represents, a hydrogen atom, alkyl group, cycloalkyl group, aryl group or aralkyl group. Also, R
1
and R
4
can be combined to form an alkylene group.)
is reacted with a secondary phosphonate ester expressed by the general formula (II):
HP(O)(OR
5
)(OR
6
) (II)
(In the formula, each of R
5
and R
6
individually represents an alkyl group, cycloalkyl group, aralkyl group, or aryl group. Also, R
5
and R
6
can be combined to form an alkylene group with a substitute group.)
It is the invention of a manufacturing method for phosphonate esters expressed as the general formula (III):
R
1
R
2
CH—CR
3
R
4
[P(O)(OR
5
)(OR
6
)] (III)
(In the formula, each of R
1
to R
6
is the same as above.).
Furthermore, the present invention is characterized such that in the presence of palladium catalyst, a diene compound expressed by the general formula (IV):
R
11
R
12
C═CR
13
—CR
14
═CR
15
R
16
(IV)
(In the formula each of R
11
to R
16
individually represents a hydrogen atom, alkyl group, cycloalkyl group, aryl group or aralkyl group. Also, R
11
and R
16
can be combined to form an alkylene group or cyclo alkylene group.) is reacted with a secondary cyclic phosphonate ester expressed by the general formula (V):
HP(O)X (V)
(In the formula, X shows the divalent group of —OC(R
17
R
18
)—C(R
19
R
20
)O—. Here, each of R
17
to R
20
shows a hydrogen atom, alkyl group, cycloalkyl group, or aryl group.)
It is the invention of a manufacturing method for allyphosphonate esters expressed by the general formula (VI):
R
11
R
12
CH—CR
13
═CR
14
—CR
15
R
16
[P(O)X] (VI)
(In the formula, R
11
to R
16
and X are the same as above.) Furthermore, it is an invention for allylphosphonate esters expressed by the general formula (VI):
R
11
R
2
CH—CR
3
═CR14—CR
15
R
16
[P(O)X] (VI)
(In the formula, R
11
to R
16
and X are the same as above.)
BEST MODE FOR CARRYING OUT THE INVENTION
The examples of the alkyl group expressed as R
1
to R
4
for the alkene compound expressed in the above-mentioned general formula (I) used for the present invention, and the alkyl group expressed as R
11
to R
16
for the diene compound expressed in the above-mentioned general formula (IV) are, alkyl groups with 1 to 18 carbons, and preferably 1 to 10 carbons. These can be either linear or branched and specific examples are, for instance, a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group.
In addition, the examples of the cycloalkyl group expressed as R
1
to R
4
and the cycloalkyl group expressed as R
11
to R
16
are, cycloalkyl groups with 5 to 18 carbons, and preferably 5 to 12 carbons. The specific examples are for instance, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclodecyl group and a cyclododecyl group.
Similarly, the examples of an aryl group are an aryl group with 6 to 14 carbons and preferably 6 to 12 carbons, and specific examples are a phenyl group, a tolyl group, an xylyl group, a naphtyl group, a methylnaphtyl group, a penbenzylphenyl group, and a biphenyl group.
Moreover, the examples of an aralkyl group are an aralkyl group with 7 to 13 carbons and preferably 7 to 11 carbons, and specific examples are for instance, a benzyl group, a methylbenzyl group, a phenethyl group, a methylphenethyl group, a phenylbenzyl group and a naphtylmethyl group.
The alkyl group, cycloalklyl group, aryl group and aralkyl group, expressed as the above-mentioned R
1
to R
4
, and the alkyl group, cycloalkyl group, aryl group and aralkyl group expressed as the above-mentioned R
11
to R
16
can be substituted with inert functional groups for the reaction, for example, alkyl groups such as a methyl group or an ethyl group, alkoxy groups such as a methoxy group or an ethoxy group, alkoxycarbonyl groups such as a methoxy carbonyl group or an ethoxy carbonyl group, a cyano group, an N,N-di-substituted amino group such as a dimethylamino group or diethylamino group, and a fluoro group.
The examples of an alkylene group in the general formula (I) in which R
1
and R
4
are combined to form an alkylene group, and the alkylene group in the general formula (IV), in which R
11
and R
16
are combined to form an alkylene group are an alkylene group with 1 to 20 carbons, and more preferably 1 to 10 carbons. Specific examples are, for instance, a methylene group, an ethylene group, a trimethylene group, and a tetramethylene group.
The examples of the cycloalkylene group in the general formula (IV) in which R
11
and R
16
are combined to form a cycloalkylene group are, cycloalkylene group with 5 to 18 carbons, and more preferably 5 to 10 carbons, and specific examples are, for instance, a cyclopentylene group, a cyclohexylene group, a cycloheptylene group, a cyclooctylene group, a cyclononylene group, and a cyclodecylene group.
The examples of an alkene compound preferably used in the present invention are, ethylene, propylene, octene, sty
Han Li-Biao
Mirzaei Farzad
Tanaka Masato
Desai Rita
National Institute of Advanced Industrial Science and Technology
Rader & Fishman & Grauer, PLLC
Shiao Robert
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