Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2000-06-01
2001-09-11
Higel, Floyd D. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S378000, C568S470000
Reexamination Certificate
active
06288283
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for producing retinal which is a basic starting material for producing carotenoids that is important in the fields of medicines, feed additives and food additives and it also relates to intermediates for producing retinal.
2. Description of Related Art
Retinal is an important basic starting material for producing carotenoids, e.g., &bgr;-carotene. As a method for the production of retinal, a method has been known, in which retinal is produced by oxidizing retinol (e.g., J. Chem. Soc. 411 (1944), JP63-233943A, Helv. Chim. Acta 40, 265 (1957) and JP7-103095B). However, this method has a problem in that it has required handling of retinol, which is sensitive to heat, light and oxygen. In addition to the above methods, the following methods are known, a method in which a carbon-increment reaction is conducted in the side chain of &bgr;-ionone which is a C13 compound (e.g., Bull. Soc. Chim. Fr. 132, 696 (1995)) and a method in which a carbon-increment reaction is conducted in a side chain of cyclocitral which is a C10 compound (Chem. Lett. 1201 (1975)). These methods, however, require, as a starting material, &bgr;-ionone or cyclocitral which is expensive on the market and produced by multistage processes. Hence, these methods are not always industrially satisfactory.
SUMMARY OF THE INVENTION
An object of the invention is to provide a process for producing retinal from relatively inexpensive starting material through an intermediate which is easy to handle, instead of labile retinol.
It is also an object of the invention to provide a novel intermediate compounds of formula (1) and (2) as well as processes for producing said intermediates from a diol derivative (3).
As shown in Scheme 1 said diol derivative (3) can be synthesized by treating a sulfone (8) with a base;
said sulfone (8) can be obtained by coupling a cyclic sulfone derivative (6) with an allyl halide derivative (7); and
said cyclic sulfone derivative (6) and said allylhalide derivative (7) can be derivatized from linalool or geraniol which is a relatively inexpensive C10 compound.
The method for producing the diol derivative (3) as shown in the scheme 1 is described in Chem. Lett. 479 (1975), JP11-130709A, JP11-130730A, JP11-222479A, JP11-236356A and JP11-236357A.
The present invention provides:
1. a hydroxyaldehyde derivative of formula (1):
wherein the wavy line depicted by
indicates a single bond and the compound having a double bond to which said single bond is attached represents E or Z isomer or a mixture thereof,
2. a process for producing the hydroxyaldehyde derivative of formula (1) as defined above, which comprises oxidizing a diol derivative of formula (3):
wherein the wavy line depicted by
indicates a single bond and the compound having a double bond to which said single bond is attached represents E or Z isomer or a mixture thereof,
3. a process for producing retinal of formula (4):
wherein the wavy line depicted by
indicates a single bond and the compound having a double bond to which said single bond is attached represents E or Z isomer or a mixture thereof,
which comprises subjecting the hydroxyaldehyde derivative of formula (1) as defined above to a dehydrating reaction,
4. a methoxy alcohol derivative of formula (2):
wherein the wavy line depicted by
indicates a single bond and the compound having a double bond to which said single bond is attached represents E or Z isomer or a mixture thereof.
5. a process for producing the methoxy alcohol derivative of formula (2) as defined above, which comprises selectively methylating a diol derivative of formula (3) as defined above,
6. a process for producing a methoxyaldehyde derivative of formula (5):
wherein the wavy line depicted by
indicates a single bond and the compound having a double bond to which said single bond is attached represents E or Z isomer or a mixture thereof,
which comprises oxidizing a methoxy alcohol derivative of formula (2) as defined above, and
7. a process as defined in item 6 above, which further comprises the step of eliminating a methoxy group of the methoxyaldehyde derivative (5) to produce a retinal of formula (4) as defined above.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the present invention, the wavy line depicted by
in formulae (1) to (8) indicates a single bond and the compound having a double bond to which said single bond is attached represents E or Z isomer or a mixture thereof. The hydroxyaldehyde derivative of formula (1) or the methoxy alcohol derivative of formula (2), for example, may represent a single geometrical isomer of all the possible isomers resulting from geometrical isomerism of each double bond to which a wavy line is attached or an optional mixture thereof.
The hydroxyaldehyde derivative (1) can be obtained by a process which comprises oxidizing the diol derivative (3) as defined above. In a similar manner, the methoxyaldehyde derivative of formula (5) also can be obtained by a process which comprises oxidizing the methoxy alcohol derivative of formula (2) and the following description refers to both the processes.
Oxidation of the diol derivative of formula (3) or the methoxy alcohol derivative of formula (2) is usually conducted with an oxidizing agent.
Examples of the oxidizing agent to be used include salts or oxides of metals such as chromium and manganese or a metal oxide of selenium. Specific examples thereof include pyridinium chlorochromate, pyridinium dichromate, manganese dioxide and selenium dioxide. The amount of the oxidizing agent is usually about 1 to 10 moles and preferably 1 to 3 moles per mol of the diol derivative (3) or the methoxy alcohol derivative of formula (2), respectively.
In the above reaction, an organic solvent is usually used. Examples of such a solvent include
a hydrocarbon solvent such as n-hexane, cyclohexane, n-pentane, n-heptane, toluene or xylene,
a halogenated solvent such as chloroform, dichloromethane, 1,2-dichloroethane, monochlorobenzene or o-dichlorobenzene,
an aprotic solvent such as N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, N,N-dimethylacetamide or hexamethylphosphoric triamide, and
an ether solvent such as 1,4-dioxane, tetrahydrofuran or anisole.
The oxidation reaction is usually conducted in a range from 0° C. to the boiling point of the solvent used.
After the reaction, the hydroxyaldehyde derivative (1) or the methoxyaldehyde derivative (5) can be obtained by a usual post-treatment such as filtration, extraction, evaporation or the like and may be further purified, for example, by silica gel chromatography, if necessary.
The hydroxyaldehyde derivative (1) can be derivatized to retinal (4) by a process which comprises dehydrating the hydroxyaldehyde derivative (1) in the presence of an acid catalyst.
Examples of the acid catalyst include triphenylphosphine hydrobromide, pyridine hydrochloride, pyridine hydrobromide, aniline hydrochloride, aniline hydrobromide, lutidine hydrochloride, lutidine hydrobromide, picoline hydrochloride, picoline hydrobromide, 2-pyridineethansulfonic acid, 4-pyridineethansulfonic acid, thionyl chloride-pyridine and paratoluenesulfonic acid-pyridine.
The amount of the acid catalyst to be used is preferably 0.05 to 2 moles per mol of the hydroxyaldehyde derivative (1).
In the above reaction, an organic solvent is usually used.
Examples of the solvent include
a hydrocarbon solvent such as n-hexane, cyclohexane, n-pentane, n-heptane, toluene or xylene,
an ether solvent such as diethyl ether, tetrahydrofuran or anisole,
a halogenated solvent such as chloroform, dichloromethane, 1,2-dichloroethane, monochlorobenzene or o-dichlorobenzene, and
an aprotic solvent such as N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, N,N-dimethylacetamide or hexamethylphosphoric triamide.
The dehydration is usually conducted in a range from −10° C. to the boiling point of the solvent used and preferably in a range from about 0° C. to 100° C. After completion of the reaction, the desired product can be obtaine
Konya Naoto
Seko Shinzo
Takahashi Toshiya
Birch & Stewart Kolasch & Birch, LLP
Higel Floyd D.
Sackey Ebenezer
Sumitomo Chemical Company Ltd.
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