Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2000-10-10
2002-09-03
Shippen, Michael L. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S031000, C568S032000
Reexamination Certificate
active
06444857
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a process for producing Vitamin A aldehyde, a key material for producing a carotenoid that is an important ingredient of pharmaceuticals, food and feed additives, and an intermediate for producing the same.
Vitamin A aldehyde is an important material for producing carotenoid such as &bgr;-carotene and a process of oxidizing retinol has been known for producing the same. However, the process has a drawback in that the process requires the use of retinol, which is very unstable to heat, light or oxygen.(e.g., J.Chem. Soc. 411 (1944), JP 63-233943A, Helv. Chim. Acta 40, 265 (1957), JP7-103095B).
There has also been known a carbon-increment reaction process at the side chain of C13 compounds such as &bgr;-ionone ( e.g., Tetrahedron Lett. 35, 7383 (1994)), or C10 compound cyclocitral (Chem. Lett. 1201 (1975)). These processes are not always advantageous from an industrial view point because commercially expensive &bgr;-ionone or cyclocitral and multistep processes are required. There has been also known a method in which a C10 cyclic sulfone compound is coupled with a C10 aldehyde dimethyl acetal compound having an allyl halide moiety in its molecule (Bull. Soc. Chim. Fr. 130, 200 (1993). The method is not always advantageous from industrial view point in that synthesis of said C10 aldehyde dimethyl acetal compound required multistep processes.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a process for producing Vitamin A aldehyde using a novel intermediate which is easy to handle and readily available from a diol derivative of the formula (2) which is obtained from a rather inexpensive C10 compound such as linalool or geraniol or the like, without using unstable retinol.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention provides:
1. An alcohol derivative of formula (1):
wherein Ar is an optionally substituted aryl group, R is a straight or branched C1-C3 lower alkyl group, and the wavy line depicted by
indicates a single bond and stereochemistry relating to a double bond bound therewith is E or Z or a mixture thereof;
2. A method for producing an alcohol derivative of formula (1) as defined above, which comprises reacting a diol derivative of formula (2):
wherein Ar and the wavy line represent the same as defined above, with a lower alcohol of formula (3):
ROH (3)
wherein R is a straight or branched C1-C3 lower alkyl group, in the presence of an acid catalyst; and
3. A method for producing an aldehyde derivative of formula (4):
wherein Ar is an optionally substituted aryl group, R is a straight or branched C1-C3 lower alkyl group and the wavy line represents the same as defined above,
which comprises reacting an alcohol derivative of formula (1) as defined above, with an oxidizing agent.
First, explanation will be made to the definitions of R and Ar in the chemical formulae (1), (2), (3) and (4) of the present specification.
Examples of the straight or branched C1-C3 alkyl group represented by R include a methyl, ethy, n-propyl and i-propyl group.
Examples of the optionally substituted aryl group represented by Ar include a phenyl group, a naphthyl group and the like, and the substituent which may be present on the said aryl groups includes
a C1-C5 alkyl group (e.g., a methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, t-butyl, n-pentyl, neo-pentyl group, and the like),
a C1-C5 alkoxy group (e.g., a methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, i-butoxy, t-butoxy, n-pentyloxy, neo-pentyloxy group, and the like),
a halogen atom (e.g., a chlorine, bromine, fluorine or iodine atom), a nitro group and the like.
Specific examples thereof include phenyl, naphthyl, o-tolyl, m-tolyl, p-tolyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-bromophenyl, m-bromophenyl, p-bromophenyl, o-iodophenyl, m-iodophenyl, p-iodophenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl and the like.
Next a description will be made to the process for producing an alcohol derivative of formula (1), which comprises reacting a diol derivative of formula (2), with a lower alcohol of formula (3), in the presence of an acid catalyst.
The acid catalyst employed in this reaction includes a Lewis acid, and a Brønsted acid. Examples of the Lewis acid include stannous chloride, stannic chloride, zinc chloride, ferric chloride, boron trifluoride ether complex and a triflate of a rare earth element such as scandium triflate, and examples of the Brønsted acid include hydrobromic acid, hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, benzoic acid, triphenylphosphine hydrobromide, pyridine hydrochloride, a heteropolyacid such as phosphotungstic acid hydrate, phosphomolybdic acid hydrate or silicotungstic acid hydrate and the acidic ion exchange resin such as a strongly acidic resin having a terminal sulfonic acid group.
The amount of an acid catalyst is usually 0.01 to 3 moles per mol of the diol derivative of formula (2).
Examples of the lower alcohol include methanol, ethanol, n-propanol, and i-propanol and the like.
Preferred are methanol, ethanol and i-propanol.
These alcohols can be usually used as a solvent .
The reaction temperature usually ranges from −78° C. to the boiling point of the solvent employed, and preferably from −10° C. to 50° C.
After completion of the reaction, the alcohol derivative (1) is usually isolated by a conventional post treatment such as extraction, evaporation, and /or recrystallization, and may be further purified by chromatography on a silica gel, if necessary.
Specific examples of the alcohol derivative of formula (1) include an alcohol compound of formula (1), wherein R is a methyl group and Ar is a tolyl group, and
further alcohol compounds of formula (1), wherein R is an ethyl, n-propyl, i-propyl group in place of the methyl group in the above-described compound and alcohol compounds of formula (1), wherein Ar represents a phenyl, naphthyl, m-tolyl, p-tolyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-bromophenyl, m-bromophenyl, p-bromophenyl, o-iodophenyl, m-iodophenyl, p-iodophenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-nitrophenyl, m-nitrophenyl, or p-nitrophenyl group in place of the tolyl group in the above-described compounds.
The aldehyde derivative (4) can be obtained by a method which comprises reacting the alcohol derivative of formula (1) with an oxidizing agent optionally in the presence of a catalyst. Examples of the oxidizing agent and the optionally used catalyst will be specified as below.
The oxidizing of the alcohol derivative (1) is usually conducted by one of the following methods and the like.
The oxidizing of the alcohol derivative (1) can be conducted by a step comprising:
(a) subjecting the alcohol derivative (1) to contact with a metal oxidant, or
(b) subjecting the alcohol derivative (1) to contact with a sulfoxide compound, a sulfoxide-activating compound and optionally a base, or
(c) subjecting the alcohol derivative (1) to contact with a sulfide compound, a halogenating agent and a base, or
(d) subjecting the alcohol derivative (1) to contact with an aldehyde in the presence of a catalyst selected from an aluminum alkoxide or aryloxide, and a boron compound, or
(e) subjecting the alcohol derivative (1) to contact with an oxygen in the presence of a catalyst.
A description will be made to the oxidizing step (a).
Examples of the metal oxidant include a salt or oxide of chromium or manganese, an oxide of nickel or selenium, or a salt of silver. Specific examples thereof include pyridinium chlorochromate, pyridinium dichromate, manganese dioxide, nickel peroxide, selenium dioxide and silver carbonate. The amount of the metal oxidant to be used is usually about 1 to 20 moles, preferably 1 to 10 moles per mol of the alcohol derivative (1).
The reaction is usually conducted in a solvent.
Konya Naoto
Seko Shinzo
Takahashi Toshiya
Birch & Stewart Kolasch & Birch, LLP
Shippen Michael L.
Sumitomo Chemical Company Limited
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