Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-09-19
2002-05-07
Powers, Fiona T. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06384231
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a method of producing 2,4-oxazolidinediones and metal salts thereof.
2,4-oxazolidinediones and metal salts thereof are compounds useful as an intermediate of a medicine.
As a method of producing metal salts of 2,4-oxazolidinediones, known are a method in which alcohol is used singly as a solvent, and a 2-hydroxycarboxylate, urea and a metal alkoxide are reacted in this solvent, a method in which a 2-hydroxycarboxylate and urea are added to a mixture of a metal alkoxide and a solvent and, then, they are mixed and reacted, and the like [J. Am. Chem. Soc., 63, 2376 (1941)]. However, the former method has a problem that the yield of the resulting metal salt of a 2,4-oxazolidinedione is low, and the latter method has a problem that relatively large amount of by-products are produced simultaneously.
Further, as a method of producing 2,4-oxazolidinediones, there is known a method in which a 2-hydroxycarboxylate, urea and a metal alkoxide are reacted in a solvent to obtain a reaction mixture containing a metal salt of a 2,4-oxazolidinedione, and an aqueous solution of an acid is added,to the resulted reaction mixture [J. Am. Chem. Soc., 63, 2376 (1941)]. However, also this production method has a problem that the yield of the resulting 2,4-oxazolidinedione is not sufficient.
The present inventors have intensively studied for solving the above-mentioned conventional problems, and resultantly found that a metal salt of 2, 4-oxazolidinedione can be obtained efficiently by reacting a 2-hydroxycaboxylate, urea and a metal alkoxide in an aromatic hydrocarbon.
Also, the present inventors have found that when a 2-hydroxycarboxylate and a metal alkoxide are added to urea, the amount of by-products produced is small.
Further, the present inventors have intensively studied for developing a method which can produce a 2,4-oxazolidinedione from a metal salt of 2,4-oxazolidinedione with high yield, and resultantly found that by adding a metal salt of 2,4-oxazolidinedione to an aqueous solution of an acid, the intended 2,4-oxazolidinedione can be obtained at high yield. Thus, the present invention was completed.
SUMMARY OF THE INVENTION
The present invention provides a method of producing a metal salt of 2,4-oxazolidinedione of the general formula (III) wherein a 2-hydroxycarboxylate of the general formula (I), urea and a metal alkoxide of the formula (II) are reacted in an aromatic hydrocarbon:
wherein, R
1
and R
2
each independently represent a hydrogen atom or a lower alkyl group, and R
3
represents a lower alkyl group;
R
4
—OM (II)
wherein, R
4
represents a lower alkyl group, and M represents an alkali metal atom;
wherein, R
1
, R
2
and M have the same meanings as described above. (hereinafter, this method is referred to as Metal salt production method 1).
The present invention also provides a method of producing a metal salt of 2, 4-oxazolidinedione of the general formula (III) wherein a 2-hydroxycarboxylate of the general formula (I) and a metal alkoxide of the formula (II) are added to urea, and, then, they are reacted. (hereinafter, this method is referred to as Metal salt production method 2).
Further, the present Invention provides a method of producing a 2,4-oxazolidinedione of the general formula (IV):
wherein, R
1
and R
2
have the same meanings as described above, wherein a metal salt of 2,4-oxazolidinedione of the general formula (III) is added to an aqueous solution of an acid. (hereinafter, this method is referred to as Production method 3).
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
As the lower alkyl group represented by R
1
, R
2
and R
3
in the general formula (I) and as the lower alkyl group represented by R
1
and R
2
in the general formulae (III) and (IV) for example, a methyl group, ethyl group, propyl group, butyl group and the like are listed.
Examples of such 2-hydroxycarboxylates include methyl glycolate, ethyl glycolate, propyl glycolate, butyl glycolate, methyl 2-hydroxypropionate, ethyl 2-hydroxypropionate, propyl 2-hydroxypropionate, butyl 2-hydroxypropionate, methyl 2-hydroxyisobutyrate, ethyl 2-hydroxyisobutyrate, propyl 2-hydroxyisobutyrate, butyl 2-hydroxyisobutyrate, methyl 2-hydroxyvalerate, ethyl 2-hydroxyvalerate, propyl 2-hydroxyvalerate, butyl 2-hydroxyvalerate, methyl 2-hydroxyhexanoate, ethyl 2-hydroxyhexanoate, propyl 2-hydroxyhexanoate, butyl 2-hydroxyhexanoate, methyl 2-hydroxy-2-methylbutyrate, ethyl 2-hydroxy-2-methylbutyrate, propyl 2-hydroxy-2-methylbutyrate, butyl 2-hydroxy-2-methylbutyrate and the like.
In any of Metal salt production method 1 and Metal Salt production method 2, the use amount of urea is usually from about 1 to 5-fold mol, preferably from about 1 to 3-fold mol based on the 2-hydroxycarboxylate.
As the lower alkyl group represented by R
4
in the general formula (II), for example, a methyl group, ethyl group, propyl group, butyl group and the like are listed. In the general formula (II), or in the general formula (III), examples of M include alkali metal atoms such as a lithium atom, sodium atom, potassium atom, and the like. Examples of such metal alkoxides include lithium methoxide, lithium ethoxide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide and the like.
In any of Metal salt production method 1 and Metal salt production method 2, the use amount the metal alkoxide is usually from about 1 to 3-fold mol, preferably from about 1 to 2-fold mol, further preferably from about 1 to 1.5-fold mol, based on the 2-hydroxycarboxylate.
In Metal salt production method 1, such a 2-hydroxycarboxylate, urea and a metal alkoxide are reacted in an aromatic hydrocarbon. As the aromatic hydrocarbon, for example, benzene, toluene, xylene, ethylbenzene and the like are listed. These may be used alone or in admixture of two or more. The use amount of the aromatic hydrocarbon is usually from about 0.5 to 10-fold by weight, preferably from about 1 to 5-fold by weight, further preferably from about 2 to 3-fold by weight, based on the 2-hydroxycarboxylate.
The reaction in Metal salt production method 1 of the present invention is conducted in an aromatic hydrocarbon, and alcohol may be allowed to be further present in this reaction. As the alcohol, for example, methanol, ethanol and the like are listed. When reacted in the presence of alcohol, the use amount thereof is usually 10-fold by weight or less, preferably 3-fold by weight or less, more preferably 0.7-fold by weight or less, based on the aromatic hydrocarbon.
For carrying out the reaction in Metal salt production method 1, for example, an aromatic hydrocarbon, urea, a 2-hydroxycarboxylate and a metal alkoxide are mixed. The reaction temperature is usually 50° C. or more and 80° C. or less, preferably 60° C. or more and 70° C. or less. When reacted in the presence of alcohol, this alcohol may also be supplied, together with a metal alkoxide, as a metal alkoxide alcohol solution in which the metal alkoxide is dissolved.
The reaction may also be conducted under reduced pressure, for example, under a pressure of from about 0.080 to 0.093 MPa. The reaction time is preferably from about 2 to 5 hours, usually.
In Metal salt production method 2, a 2-hydroxycarboxylate and a metal alkoxide are added to urea and, then, they are reacted. Usually, a 2-hydroxycarboxylate and a metal alkoxide are added to a mixture o urea and a solvent.
As the solvent, aromatic hydrocarbons, alcohols and the like are listed, and preferable are aromatic hydrocarbons. As the aromatic hydrocarbon, for example, benzene, toluene, xylene, ethylbenzene and the like are listed. As the alcohol, for example, methanol, ethanol and the like are listed. These may be used alone or in combination of two or more. The use amount of a solvent in Metal salt production method 2 is usually from about 0.5 to 10-fold by weight, preferably from about 1 to 5-fold by weight, more preferably from about 2 to 3-fold by weight based on the used 2-hydroxyoarboxylate.
The reaction of Metal salt production method 2 is us
Kamikawa Takashi
Nakamura Keiko
Powers Fiona T.
Sumitomo Chemical Company Limited
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