Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2000-01-28
2001-01-09
Barts, Samuel (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S648000, C568S649000, C568S656000
Reexamination Certificate
active
06172268
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method for producing an optically active 1-substituted 2-propanol which is useful as a starting material for pharmaceuticals or agricultural chemicals, particularly as an intermediate for synthetic antibacterial agents.
2. Discussion of Background
The following methods have been proposed for the synthesis of optically active 1-aryloxy-2-propanols among optically active 1-substituted 2-propanols.
(1) A method of reacting optically active 2-O-tetrahydropyranylpropane-1,2-diol with a fluorobenzene derivative (EP322815A).
(2) A method of reacting optically active 2-O-tetrahydropyranylpropane-1,2-diol with a phenol derivative by means of a Mitsunobu reagent (JP-A-1-250369).
(3) A method of reducing a 1-aryloxy-2-propanone by means of a microorganism (JP-A-3-183469, JP-A-5-68577).
(4) A method of converting a racemic modification of a 1-aryloxy-2-propanol to an optically active 1-aryloxy-2-acyloxypropane by means of a microorganism, followed by hydrolysis (JP-A-4-267890).
However, the above methods have the following problems.
The methods (1) and (2) require many steps for the synthesis of the optically active starting material. The methods (3) and (4) utilize microorganisms and thus have drawbacks specific to microbial reactions. For example, they have problems such that the volume efficiency is poor, and an antipode having an absolute configuration opposite to the desired optically active substance, will be obtained. Namely, the conventional methods have had problems in their industrial application.
SUMMARY OF THE INVENTION
The present invention has been made to solve the above problems, and it is an object of the present invention to provide a method for producing an optically active 1-substituted 2-propanol which is useful as an intermediate for e.g. synthetic antibacterial agents. That is, the present invention provides a method for producing an optically active 1-substituted 2-propanol of the following formula 1, which comprises reacting a hydroxy aromatic compound of the following formula 2 with, an optically active propylene oxide in the presence of a catalyst:
AOH Formula 2
CH
3
C*H(OH)CH
2
OA Formula 1
wherein A is a univalent aromatic group, and C* is an asymmetric carbon atom.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Now, the present invention will be described in detail.
In the hydroxy aromatic compound (formula 2) in the present invention, A is a univalent aromatic group having one hydrogen atom on an aromatic ring removed from a compound having the aromatic ring. The compound having the aromatic ring may, for example, be an aromatic hydrocarbon compound such as benzene, naphthalene, anthracene, biphenyl or indene, a compound having an aromatic hetero ring such as pyridine, furan, thiophene, pyridazine, pyrimidine, pyrazine, 1,3,5-triazine, isoquinoline, quinoxaline or naphthylizine, or an aromatic hydrocarbon compound or a compound having a hetero ring, which has a substituent.
In the present invention, A is preferably an aryl group Which is a residue having one hydrogen atom removed from an aromatic hydrocarbon compound, or a substituted aryl group. Namely, as the hydroxy aromatic compound (formula 2) in the present invention, a hydroxyaryl compound of the following formula 2a, is preferred:
A
r
OH Formula 2a
wherein A
r
is an aryl group or a substituted aryl group.
When A
r
is a substituted aryl group, such a substituted aryl group is a group having at least one hydrogen atom in the aryl group substituted by a substituent. As such a substituent, a halogen atom, a nitro group, a cyano group, a carbamoyl group, a monoacylamino group or a diacylamino group is, for example, preferred. As the halogen atom, a chlorine atom, a bromine atom or a fluorine atom is preferred. As the monoacylamino group, an acetylamino group is preferred, and as the diacylamino group, a diacetylamino group is preferred.
As the substituted aryl group, a substituted phenyl group is preferred. The number of substituents in the substituted phenyl group is preferably from 1 to 4, particularly preferably from 1 to 3. Further, when the number of substituents in the substituted phenyl group is two or more, such substituents may be the same or different.
The following compounds may be mentioned as specific examples of the hydroxy aromatic compound (formula 2) in the present invention. However, there is no particular limitation as to the positions at which the hydroxyl groups and the substituents are bonded in the following hydroxy aromatic compounds.
Examples of the hydroxy aromatic compound (formula 2) other than the hydroxyaryl compound (formula 2a):
Hydroxypyridine, fluorohydroxypyridine, chlorohydroxypyridine, trifluoromethylhydroxypyridine, hydroxyfuran, fluorohydroxyfuran, chlorohydroxypyrimidine, hydroxypyrazine, chlorohydroxyisoquinoline, and hydroxynaphthylidine.
Examples of the hydroxyaryl compound (formula 2):
Phenol, nitrophenol, cyanophenol, chlorophenol, fluorophenol, chloronitrophenol, fluoronitrophenol, chlorofluoronitrophenol, and difluoronitrophenol.
In the present invention, the hydroxy aromatic compound (formula 2) is preferably a hydroxyaryl compound (formula 2a), particularly preferably a compound of the formula (formula 2a) wherein Ar is a substituted phenyl group. Further, the hydroxyaryl compound (formula 2a) is preferably one wherein Ar is a phenyl group substituted by a nitro group and a halogen atom. As such a halogen atom, a fluorine atom and/or a chlorine atom is preferred.
Further, the hydroxyaryl compound (formula 2a) is preferably a nitrophenol of the following formula 2b:
wherein X is a fluorine atom or a chlorine atom.
Further, the following compounds may be mentioned as specific examples other than nitrophenols (formula 2b) among hydroxy aromatic compounds (formula 2) of the present invention.
6-Chloro-2-nitrophenol,
5-chloro-2-nitrophenol,
4-chloro-2-nitrophenol,
3-chloro-2-nitrophenol,
6-fluoro-2-nitrophenol,
5-fluoro-2-nitrophenol,
4-fluoro-2-nitrophenol,
3-fluoro-2-nitrophenol.
The following compounds may be mentioned as specific examples of the nitrophenols (formula 2b).
2-Chloro-3-fluoro-6-nitrophenol,
2,3-difluoro-6-nitrophenol.
In the present invention, the hydroxy aromatic compound (formula 2) is reacted with an optically active propylene oxide.
The optically active propylene oxide is a propylene oxide which contains either a propylene oxide wherein the absolute configuration of asymmetric carbon atom is R (i.e. R-propylene oxide) or a propylene oxide wherein such an absolute configuration is S (i.e. S-propylene oxide) excessively. The optical active propylene oxide may be one containing either R-propylene oxide or S-propylene oxide excessively.
The reaction of the present invention proceeds while the absolute configuration of the asymmetric carbon atom of the propylene oxide is maintained. Accordingly, a propylene oxide may be employed which has an absolute configuration corresponding to the absolute configuration of the desired compound. The optically active propylene oxide can be obtained by e.g. kinetic resolution as disclosed in a literature (Science, 277, 936 (1997)). The optically active propylene oxide is preferably one having an optical purity of from 0.1 to 100% ee (enantio excess), more preferably from 10 to 100% ee, most preferably from 30 to 100% ee.
The optically active propylene oxide is used preferably in an amount of from 10 to 500 mol %, more preferably from 50 to 300 mol %, to the hydroxy aromatic compound (formula 2).
The reaction of the present invention is carried out in the presence of a catalyst. As the catalyst, alumina, a base or a metal complex compound is, for example, preferred. The alumina may, for example, be W-200 (tradename, manufactured by Woelm Co.), and the base may be an organic base or an inorganic base. The organic base is preferably triethylamine or diisopropylethylamine, and the inorganic base is preferably sodium hydroxide, sodium carbonate, sodium hydrogencarbonate, potassium hydroxid
Asai Tomoyuki
Tohma Toshihiko
Asahi Glass Company Limited
Barts Samuel
Davis Brian J.
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
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