Organic compounds -- part of the class 532-570 series – Organic compounds – Sulfur containing
Reexamination Certificate
1999-06-09
2001-04-03
Vollano, Jean F. (Department: 1609)
Organic compounds -- part of the class 532-570 series
Organic compounds
Sulfur containing
C568S032000, C568S034000, C568S447000, C568S446000
Reexamination Certificate
active
06211411
ABSTRACT:
DETAILED DESCRIPTION OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for producing retinal, 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.
2. Description of the Related Art
Retinal is an important material for producing carotenoid such as &bgr;-carotene and a process has been known for producing the same by oxidizing retinol. However, the process has a drawback in that the process requires the use of retinol, which is very unstable to heat, light and 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 citral (Chem. Lett. 1201 (1975)). These processes are not always advantageous from an industrial view point because commercially expensive &bgr;-ionone or citral, which are produced by multistep processes, is required.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a process for producing retinal by using a novel intermediate which is easy to handle and readily available from a sulfone derivative of the formula (6) which is obtained from inexpensive materials as depicted in Scheme 1 below by using a coupling reaction of a C10 allyl halide derivative (5) with a C10-cyclic sulfone derivative (4) which can be derivatized from a rather inexpensive C10 compound such as linalool or geraniol or the like, such that a new synthetic process to retinal without using unstable retinol is completed.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention provides:
1. A sulfone aldehyde derivative of the Formula (1):
wherein Ar is an optionally substituted aryl group;
2. A method for producing a sulfone aldehyde derivative of the Formula (1) as defined above, which comprises subjecting a sulfone derivative of the Formula (2):
wherein Ar is an optionally substituted aryl group, and R is a hydrogen atom or a protective group for a hydroxy group, to an elimination reaction, whereby eliminating the OR group;
3. A sulfone derivative of the Formula (2) as defined above,
4. A method for producing a sulfone derivative of the Formula (2) as defined above, which comprises oxidizing a hydroxysulfone derivative of the Formula (3):
wherein Ar and R are the same as defined above; and
5. A method for producing retinal, which comprises contacting the sulfone aldehyde derivative of the Formula (1 ) as defined above with a base.
First, explanation will be made to the definitions of R and Ar in the chemical formulae (1), (2) and (3) of the present specification.
R represents a hydrogen atom or a protective group for a hydroxyl group. Examples of the protective group include:
an acyl group such as acetyl, pivaloyl, benzoyl, p-nitrobenzoyl and the like,
a silyl group such as trimethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl and the like,
a tetrahydropyranyl group, alkoxymethyl group such as methoxymethyl, methoxyethoxymethyl, 1-ethoxyethyl and the like,
a benzyl group, p-methoxybenzyl group, t-butyl group, trityl group, 2,2,2-trichloroethoxycarbonyl group, an allyloxycarbonyl group and the like.
Ar represents an optionally substituted aryl group. Examples of the aryl group includes phenyl group, naphthyl group and the like, and the substituent 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.
The sulfone aldehyde derivative of the Formula (1) above can be produced by a method which comprises subjecting the sulfone derivative of the Formula (2) to an elimination reaction, whereby the OR group is eliminated.
When R in the sulfone derivative (2) is a hydrogen atom, the elimination reaction to produce the sulfone aldehyde derivative (1) is usually effected by subjecting the sulfone derivative (2) to a dehydration reaction in the presence of an acid catalyst.
The acid catalyst employed in this reaction includes a Lewis acid, a Brønsted acid, a heteropolyacid, an acidic ion exchange resin, an acid chloride and the like. Examples of the Lewis acid include zinc chloride, boron trifluoride ether complex and a triflate of a rare earth element such as scandium triflate, and examples of a Brønsted acid include hydrobromic acid, hydrochloric acid, sulfuric acid, sulfonic acid, triphenylphosphine hydrobromide, pyridine hydrochloride and benzoic acid, and the acidic ion exchange resin may be a strongly acidic resin having a terminal sulfonate group.
Examples of the acid chloride include thionyl chloride, phosphorus oxychloride and the like.
The amount of an acid catalyst is usually 0.1 to 1 molar equivalent, alternatively 0.1 to 1 part by weight based on a sulfone derivative (2).
The reaction described above usually employs an organic solvent including a hydrocarbon solvent such as n-hexane, n-heptane, cyclohexane, n-pentane, toluene, xylene and the like, an ether solvent such as 1,4-dioxane, diethylether, tetrahydrofuran, anisol and the like, a halogenated solvent such as chloroform, dichloromethane, 1,2-dichloroethane, monochlorobenzene, o-dichlorobenzene and the like, an aprotic polar solvent such as N,N-dimethylformamide, dimethylsulfoxide, N,N-dimethylacetamide, hexamethylphosphoric triamide and the like.
The reaction temperature usually ranges from −78° C. to the boiling point of the solvent employed, and preferably from −10° C. to 60° C. The reaction time may vary depending on the types of the catalyst and the temperature employed in the reaction, and usually ranges from 1 hour to 24 hours.
After the reaction, the sulfone aldehyde 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.
When R in the sulfone derivative (2) is a protective group for a hydroxyl group, then the sulfone aldehyde derivative (1) can be obtained by an elimination reaction in the presence of a palladium catalyst, whereby the OR is removed. The reaction is usually effected, for example, by a method which comprises contacting the sulfone derivative (2) with a palladium catalyst.
Examples of the palladium catalyst employed in the reaction described above include tetrakis(triphenylphosphine)palladium, palladium acetate, palladium propionate, dichlorobis(triphenylphosphine)palladium, di-p-chlorobis(&eegr;-allyl)palladium, dichloro(&eegr;-1,5-cyclooctadiene)palladium, dichloro(&eegr;-2,5-norbornadiene)palladium, dichlorobis(acetonitrile)palladium, dichlorobis(benzonitrile)palladium, dichlorobis(N,N-dimethylformamide)palladium, bis(acethylacetonato)palladium, bis(dimethylglyoxymato)palladium and the like. When a divalent palladium catalyst is employed, it is preferred to use a phosphine together.
The amounts of the catalyst and a phosphine to be used is usually 1 to 10 molar % based on the sulfone derivative of the Formula (2).
The reaction described above usually employs an organic solvent including an ether solvent such as 1,4-dioxane, tetrahydrofuran and the like, a hydrocarbon solvent such as n-hexane, n-heptane, cyclohexane, n-pentane, toluene, xylene and the like, a halogenated solvent such as chloroform, dichloromethane, 1,2-dichloroethane, monochlorobenze
Konya Naoto
Seko Shinzo
Takahashi Toshiya
Sughrue Mion Zinn Macpeak & Seas, PLLC
Sumitomo Chemical Company Limited
Vollano Jean F.
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