Organic compounds -- part of the class 532-570 series – Organic compounds – Sulfur containing
Reexamination Certificate
2001-10-18
2003-12-09
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Sulfur containing
C568S824000
Reexamination Certificate
active
06660888
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to sulfone compounds that are useful intermediate compounds for the production of pharmaceuticals, feed additives or food additives such as retinol, and production methods for producing the same, and a process for the production of retinol using the same.
BACKGROUND OF THE INVENTION
There has been disclosed a process for producing retinol by reacting a sulfone of formula (6) shown below with a C10 aldehyde compound derived from linalool by a plurality of steps to obtain a C20 hydroxy sulfone compound, and derivatizing the same by a plurality of steps (U.S. Pat. No. 4,825,006). However, there is a demand for the development of a further improved industrial production process for producing retinol.
SUMMARY OF THE INVENTION
According to the present invention, retinol can be readily obtained by using novel sulfone compounds and a readily available C5 allyl halide compound.
The present invention provides
1. a disulfone compound of formula (1):
wherein Ar denotes a substituted or unsubstituted aryl group, R
1
denotes a hydrogen atom or a protective group of a hydroxyl group and the wavy line means that the disulfone compound is an E or Z geometrical isomer or a mixture thereof;
2. a process for producing the disulfone compound of formula (1) as defined above, which comprises reacting an allylsulfone of formula (2):
wherein Ar and the wavy line have the same meanings as defined in connection with formula (1) above, with an allyl halide compound of formula (3):
wherein X denotes a halogen atom, R denotes a protective group of a hydroxyl group and the wavy line has the same meanings as defined above, in the presence of a base selected from an alkyl lithium, an alkali metal alkoxide, an alkali metal amide, an alkali metal hydride, or an alkali metal hydroxide, and optionally deprotecting;
3. a process for producing retinol, which comprises reacting the disulfone compound of formula (1):
wherein Ar, R
1
and the wavy line have the same meaning as defined above, with a base selected from an alkali metal alkoxide, an alkali metal amide, an alkali metal hydride, or an alkali metal hydroxide, and optionally deprotecting;
4. an allylsulfone compound of formula (2):
wherein Ar and the wavy line have the same meanings as defined above;
5. a process for producing an allylsulfone compound of formula (2) as defined above, which comprises reacting the sulfone compound of formula (4):
wherein R, Ar and the wavy line have the same meanings as defined above, with an arylsulfinate of formula (5):
ArSO
2
M (5)
wherein Ar has the same meaning as defined above in connection with formula (1), and M denotes an alkali metal, in the presence of a palladium catalyst; and
6. a process for producing a sulfone of formula (4) as defined above, which comprises reacting a sulfone of formula (6):
wherein Ar has the same meaning as defined above, with an allyl halide compound of formula (3):
wherein X, R and the wavy line have the same meanings as defined above, in the presence of a base selected from an alkyl lithium, an alkali metal alkoxide, an alkali metal amide, or an alkali metal hydride.
DETAILED DESCRIPTION
A description will be made to the substituent groups in formulae (1) through (6).
Examples of the protective group represented by R1 or R in the present specification include, for example, an acyl group, a silyl group, tetrahydropyranyl group, an alkoxymethyl group (e.g. a methoxymethyl group, a methoxyethoxymethyl group and the like), 1-ethoxyethyl group, a p-methoxybenzyl group, a t-butyl group, a trityl group, and an alkoxy carbonyl group such as 2,2,2-trichloroethoxycarbonyl group, allyloxycarbonyl or the like.
Examples of the acyl group include, for example,
a C
1
-C
6
alkanoyl group, which may be substituted with a halogen atom or an alkoxy group, and
a benzoyl group, which may be substituted with a halogen atom, a hydroxy group, an alkoxy group, an acetoxy group, a nitro group or the like.
Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Specific examples of the C
1
-C
6
alkanoyl group, which may be substituted with a halogen atom or an alkoxy group include, for example, a formyl, acetyl, ethoxyacetyl, fluoroacetyl, difluoroacetyl, trifluoroacetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, bromoacetyl, dibromoacetyl, tribromoacetyl, propionyl, 2-chloropropionyl, 3-chloropropionyl, butyryl, 2-chlorobutyryl, 3-chlorobutyryl, 4-chlorobutyryl, 2-methylbutyryl, 2-ethylbutyryl, valeryl, 2-methylvaleryl, 4-methylvaleryl, hexanoyl, isobutyryl, isovaleryl, pivaloyl, or the like.
Examples of the benzoyl group, which may be substituted with a halogen atom, a hydroxy group, an alkoxy group, an acetoxy group, a nitro group or the like include, for example, a benzoyl, an o-chlorobenzoyl, m-chlorobenzoyl, p-chlorobenzoyl, o-hydroxybenzoyl, m-hydroxybenzoyl, p-hydroxybenzoyl, o-acetoxybenzoyl, o-methoxybenzoyl, m-methoxybenzoyl, p-methoxybenzoyl and p-nitrobenzoyl group.
Examples of the silyl group include, for example, a trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl group and the like.
Preferred protective group is an acyl group (e.g. acetyl group and the like).
Examples of the unsubstituted or substituted aryl group represented by “Ar” include, for example, a phenyl group and a naphthyl group, and a phenyl or naphthyl group substituted with a straight or branched C1-C5 alkyl group, a straight or branched C1-C5 alkoxy group, a halogen atom, a nitro group or the like.
Examples of the C1-C5 alkyl group include, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a sec-butyl group, a t-butyl group, an isobutyl group, a n-pentyl group, a t-amyl group, and the like.
Examples of the C1-C5 alkoxy group include, for example, a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a sec-butoxy group, a t-butoxy group, an isobutoxy group, a n-pentoxy group, a t-amyloxy group and the like.
Specific examples of the unsubstituted or substituted aryl group include, for example, 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 and p-nitrophenyl and the like. Preferred are a phenyl group, a tolyl group and the like.
The disulfone compound of formula (1) can be obtained, for example, by a process of reacting the allylsulfone compound of formula (2) with an allyl halide compound of formula (3) in the presence of a base selected from an alkyl lithium, an alkali metal alkoxide, alkali metal amide, alkali metal hydride or an alkali metal hydroxide.
Examples of the halogen atom represented by X in formula (3) typically include a chlorine atom, a bromine atom, and an iodine atom.
Specific examples of the allyl halide compound of formula (3) include, for example, an ally halide compound of formula (3), wherein X is a bromine atom, and R is an acetyl group.
Examples of the alkyl lithium include, for example, n-butyl lithium, sec-butyl lithium, t-butyl lithium and the like.
Examples of the alkali metal alkoxide include, for example, a C1-C5 alcoholate of an alkali metal such as sodium methoxide, potassium methoxide, lithium methoxide, sodium ethoxide, potassium ethoxide, lithium ethoxide, potassium t-butoxide, sodium t-butoxide, lithium t-butoxide, sodium t-amylate, potassium t-amylate and the like.
Examples of the alkali metal amide include, for example, lithium amide, potassium amide, sodium amide, lithium diisopropylamide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, lithium hexamethyldisilazide and the like.
Examples of the alkali metal hydride include, for example, sodium hydride, potassium hydride, lithium hydride and the like.
Examples of the alkali metal hydroxide include, for example, sodium hydroxide, potassium hydroxide and lithium hydroxide.
Any b
Doi Noriyuki
Kimura Kazutaka
Konya Naoto
Seko Shinzo
Takahashi Toshiya
Birch & Stewart Kolasch & Birch, LLP
Sumitomo Chemical Company Limited
Vollano Jean F.
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