JP3218360B2 - Ozonide reducing agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an ozonide reducing agent which is widely used, is industrially safe, is inexpensive, and can be easily worked up.

[0002]

2. Description of the Related Art Conventionally, the ozonolysis reaction has been widely and generally carried out as a method for obtaining carboxylic acids, aldehydes, ketones and epoxides from organic unsaturated compounds and aromatic compounds, and is commonly used industrially. It is a reaction (New Experimental Chemistry Course Vol.15 [I-2] Chapter 10, Publication year;
Published on September 20, 1975, published by Maruzen Co., Ltd.). Usually, the ozonolysis reaction is carried out by subjecting an organic unsaturated compound and an aromatic compound to ozone to obtain an intermediate called ozonide (peroxide) and subjecting the ozonide to oxidation, reduction, hydrolysis and the like. The present invention relates to the latter half of the process, which comprises two steps of extracting a stable target compound. Ozonide in the present invention means any peroxide generated by an ozonolysis reaction such as α-ozonide, β-ozonide, hydroxyperoxide, diperoxide, etc. Can be said to be a key step of the ozonolysis reaction.

In general, it is said that the mildest and least side-reaction method among ozonide treatment methods is reductive decomposition treatment (New Experimental Chemistry Lecture, Vol. 15, [I-2], Chapter 10, published year; (Published by Maruzen Co., Ltd. on September 20, 1975), and various ozonide reducing agents have been used. However, every ozonide reducing agent has some problems. Problems of each ozonide reducing agent are shown in the following (1) to (7).

(1) Reduction of acetic acid-zinc (J. Org. Chem.,2
5, 618 (1960)), compounds decomposed by acids and
It cannot be used for compounds that require a solution.
Industrial waste such as lead is a problem in pollution countermeasures.
I don't.

(2) Catalytic hydrogenation in the presence of a metal catalyst such as Pt, Pd and Ni (J. Am. Oil Chem. Soc., 42 , 236)
In the case of (1965)), hydrogen is passed through the peroxide solution in the presence of an active metal, so there is always a danger of explosion. Further, in a halogen-based solvent, since the solvent itself is reduced by hydrogenation, the type of the solvent used is limited.

(3) Reduction using metals such as Raney nickel and sodium borohydride (Can. J. Chem., 48 , 1105)
(1962)) is disadvantageous because the metal after treatment becomes industrial waste and poses a problem for pollution control.

(4) Reduction using trivalent phosphorus compounds such as triphenylphosphine and phosphite (J. Org. Che)
m., 27 , 4498 (1962)), it is not always easy to remove the phosphine oxide from the reaction system after the treatment, whereas in the case of phosphite, its peculiar odor becomes an environmental problem. Furthermore, it is not advantageous in terms of environment and facilities, for example, in some cases, a closed system must be provided due to strict phosphorous wastewater discharge standards.

(5) Reduction using dimethyl sulfide, which is most commonly used in the laboratory (Tetrahedron Letters, 19
66, 4273), although having a very high reducing power, have environmental problems due to a peculiar unpleasant odor and a problem of handling low flash point compounds, which makes industrial use difficult.

(6) In the reduction using dialkyl disulfides or thiols (J. Org. Chem., 26 , 4912 (1961)), the reducing ability is inferior to that of the above-mentioned sulfides, and a peculiar unpleasant odor is produced. And lacks versatility due to side reactions such as cleavage of disulfide bonds and addition of thiols.

(7) Further, as other sulfur-based ozonide reducing agents, those described in literatures and patents include thiourea (tetrahedron letters, 1983, 236).
7), sodium bisulfite (Helv. Chim. Acta., 21 , 748 (193)
8)), sulfur dioxide (J. Am. Chem. Soc., 75 , 3371 (1953))
However, thiourea and sodium bisulfite are used after being dissolved in water. Therefore, when low temperature is required, they can be frozen and become unusable. For sulfur dioxide, sulfur dioxide gas is generated. Disadvantages.

As described above, an ozonide reducing agent which satisfies all of the problems of economy, safety, yield, ease of post-treatment, working environment and the like and which can be used under all reaction conditions is not yet available. Not found.

[0012]

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned problems of an ozonide reducing agent in a conventional ozonolysis reaction.

[0013] That is, one object of the present invention is to provide an ozonide reducing agent which can perform reductive decomposition treatment of ozonide in a wide range of reaction temperatures without causing any side reaction in any reaction solvent.

Another object of the present invention is to provide an ozonide reducing agent which can be easily removed from the reaction system even after the treatment to obtain an ozonolysis reaction target in a high yield.

Another object of the present invention is to provide an ozonide reducing agent which does not require extra facilities in terms of environment and safety.

The present inventors have focused on sulfides having the most reducing power among the organic reducing agents in solving the above-mentioned problems of the known ozonide reducing agents in the ozonolysis reaction. did. That is, sulfides represented by dimethyl sulfide have two-coordinate sulfur, and are easily oxidized by active oxygen such as ozonide due to the electron sharing resonance stabilizing effect of oxidized sulfoxide (in other words, If so, it is expected that the reductive decomposition reaction of ozonide is likely to occur) (Daikamo, Organic Sulfur Chemistry -Reaction Mechanism-, published year; September 1, 1982, publisher; Kagaku Dojin, Ltd.). However, although sulfides can be expected to have such a high reducing ability, they have the above-mentioned odor problem and problems as low flash point compounds. In order to avoid this, the present inventor has conducted various studies, and by introducing a polar functional group to these sulfides, the effect of decreasing the vapor pressure and increasing the boiling point while maintaining the high reducing ability of the sulfides is maintained. The present inventors have obtained a new finding that a desired ozonide reducing agent can be obtained by reducing malodor and improving safety, and have completed the present invention.

By the way, sulfides into which a polar functional group is introduced, that is, compounds in which a hydrocarbon residue having a polar functional group such as a hydroxyl group, a nitrile group, or a carboxyl group as a substituent at both ends of bi-coordinated sulfur is introduced. Among them, bis (hydroxy) alkyl sulfide derivatives are, for example, antioxidants for plastics such as polypropylene and polyester (JP-A-54-43536) and antioxidants for lubricating oils (JP-A-3-502093). Antioxidants for inks and paints (JP-A-55-16916), fabric softeners (JP-B-60-9968),
It is a widely used inexpensive compound that is widely used as a catalyst pretreatment agent (Japanese Patent Application Laid-Open No. 5-154394) and is industrially mass-produced. However, no examples have been reported in which these bis (hydroxyalkyl) sulfide derivatives and mixtures thereof were used as an ozonide reducing agent in an ozonolysis reaction.

The ozonide reducing agent of the present invention is a compound having a hydrocarbon residue substituted with a polar functional group at both ends of sulfur.

In the ozonide reducing agent of the present invention, the above hydrocarbon residues at both ends of sulfur may be the same or different. Examples of the polar functional group include a hydroxyl group, a nitrile group, and a carboxyl group.

The ozonide reducing agent of the present invention includes a general formula XR ¹ -R ² -SR ³ -R ⁴ -Y (1) wherein R ¹ and R ⁴ are the same or different, Indicates a single bond or an aliphatic hydrocarbon residue. R ² and R ³ are the same or different and each represents a saturated or unsaturated aliphatic hydrocarbon residue, alicyclic hydrocarbon residue or aromatic hydrocarbon residue. X and Y are the same or different and each represents a hydroxyl group, a nitrile group or a carboxyl group. A compound represented by the formula:
Formula ^{R 5 -S-R 6 (2} ) wherein, R ⁵ and R ⁶ are the same or different, a hydroxyl group, a hydroxymethyl group, comprising a nitrile group, a cyanomethyl group, a carboxyl group and carboxymethyl group as a substituent A heterocyclic group having at least one group selected from the group is shown. And the like.

In the general formula (1), examples of the saturated or unsaturated aliphatic hydrocarbon residue represented by R ² and R ³ include a linear or branched C _1-6 alkylene group,
Examples thereof include a linear or branched C _2-8 alkenylene group and a linear or branched C _2-6 alkynylene group. Examples of the linear or branched C _1-6 alkylene group include a methylene group, an ethylene group, a trimethylene group, a 2-methyltrimethylene group, a 2,2-dimethyltrimethylene group, a 1-methyltrimethylene group, Examples thereof include a methylmethylene group, an ethylmethylene group, a tetramethylene group, a pentamethylene group, and a hexamethylene group. Examples of the linear or branched C _2-8 alkenylene group include a vinylidene group, a propenylene group, a pentylene group and a 4-propyl-2-pentylene group. Examples of the linear or branched C _2-6 alkynylene group include an ethynylene group and a propynylene group.

Examples of the alicyclic hydrocarbon residue represented by R ² and R ³ include C _3-8 cycloalkylene such as a cyclopentylene group and a cyclohexylene group.

Examples of the aromatic hydrocarbon residue represented by R ² and R ³ include a phenylene group, and a C _1-6 alkyl group such as a methyl group or an amino group is substituted on the phenylene group. Is also good.

Examples of the aliphatic hydrocarbon residue represented by R ¹ and R ⁴ include a linear or branched C _1-6 alkylene group. Examples of the linear or branched C _1-6 alkylene group include a methylene group, an ethylene group, a trimethylene group, a 2-methyltrimethylene group, a 2,2-dimethyltrimethylene group, a 1-methyltrimethylene group, Examples thereof include a methylmethylene group, an ethylmethylene group, a tetramethylene group, a pentamethylene group, and a hexamethylene group.

As the ozonide reducing agent represented by the general formula (1), R ¹ and R ⁴ are the same or different and each represents a single bond or a linear or branched C _1-6 alkylene group;
R ² and R ³ are the same or different and each is a straight-chain or branched C
_1-6 alkylene group, linear or branched C _2-8 alkenylene group, linear or branched C _2-6 alkynylene group, C _3-8 cycloalkylene group or phenyl ring C on
Preferred examples include an ozonide reducing agent which represents a phenylene group which may be substituted by a _1-6 alkyl group and / or amino group, and wherein X and Y are the same or different and each represents a hydroxyl group, a nitrile group or a carboxyl group. R ¹ and R ⁴ each represent a single bond, R ² and R ³ each represent a linear C _1-6 alkylene group, and X and Y each represent a hydroxyl group or a nitrile group. Reducing agents are particularly preferred.

Specific examples of the ozonide reducing agent represented by the above general formula (1) include, for example, bis (hydroxyalkyl) sulfide derivatives [more specifically, thiodimethanol, thiodiethanol, thiodipropanol, thiodiisopropanol] , Thioditertiary butanol, thiodipentanol, thiodihexanol, thiodiethylene glycol, thiodicyclopentanol, thiodicyclohexanol, etc.], bis (hydroxyalkenyl) sulfide derivatives [more specifically, thiodivinyl alcohol, Dipropenyl alcohol, thiodibutenyl alcohol, thiodipentenyl alcohol, etc.), bis (hydroxyalkynyl) sulfide derivatives [more specifically, thiodipropargyl alcohol, etc.], bis (hydroxyaryl) sulfide derivatives [More specifically, thiodiphenol, thiodicresol, bis (2-hydroxymethylphenyl) disulfide, bis (3-hydroxyethylphenyl) disulfide, bis (4-hydroxyallylphenyl) disulfide, thiodihydroxyaniline, etc.] , Bis (cyanoalkyl) sulfide derivatives [more specifically, thiodipropionitrile, thiodibutyronitrile, etc.], bis (cyanoalkenyl) sulfide derivatives [more specifically, thiodiacrylonitrile, etc.], bis (carboxyalkyl) Sulfide derivatives [more specifically, thiodipropionic acid, thiodiisobutyric acid, etc.], bis (carboxyalkenyl) sulfide derivatives [more specifically, thiodioleic acid, thiodifumaric acid, etc.], hydroxyalkylhydroxyalkenyl sulfide Derivative [More specifically hydroxyethyl hydroxybutyl the polybutenyl sulfides), (hydroxypropyl hydroxyethyl, more particularly propargyl sulfide, etc.] hydroxyalkyl hydroxyalkynyl sulfide derivatives, hydroxyalkenyl hydroxyalkynyl
Sulfide derivatives (more specifically, hydroxypropenyl hydroxypropargyl sulfide, etc.), hydroxyalkyl carboxyalkyl sulfide derivatives (more specifically, hydroxyethyl carboxypropyl sulfide, etc.), hydroxyalkyl cyanoalkyl sulfide derivatives (more specifically, hydroxyethyl Cyanopropyl sulfide, etc.), hydroxyalkyl 4-hydroxy-alkylphenyl sulfide derivative [more specifically, hydroxyethyl 4-hydroxy-3-methylphenyl sulfide, etc.], cyanoalkyl 4-hydroxyphenyl sulfide derivative [more specifically, Cyanoethyl 4-hydroxyphenyl sulfide, etc.), cyanoalkyl cyanoalkenyl sulfide derivative [more specifically, cyanop Ropil
Cyanobutenyl sulfide, etc.), cyanoalkyl carboxyalkyl sulfide derivative (more specifically, cyanoethyl carboxypropyl sulfide, etc.),
Cyanoalkylcarboxyalkenyl sulfide derivative (more specifically, cyanoethyl carboxypropenyl sulfide, etc.), cyanoalkenyl carboxyalkyl sulfide derivative (more specifically, cyanobutenyl carboxypropyl sulfide, etc.), cyanoalkenyl carboxyalkenyl sulfide derivative (more specifically, Cyanobutenyl carboxypropenyl
Sulfide etc.], cyanoalkenyl carboxyalkynyl sulfide derivatives [more specifically, cyanobutenyl carboxypropargyl sulfide etc.] and the like. These may be used alone or in combination of two or more.

In the above general formula (2), R ⁵ and R ⁶
Represented by a hydroxyl group, a hydroxymethyl group, a nitrile group, a cyanomethyl group, a heterocyclic group having at least one group selected from the group consisting of a carboxyl group and a carboxymethyl group as a substituent, thienyl Groups, furyl, pyridyl, pyranyl, pyrrolyl, chromenyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, pyrazinyl, pyrimidyl, pyrimidyl, quinolyl and the like.

Examples of the ozonide reducing agent represented by the general formula (2) include a thienyl group having R ⁵ and R ⁶ each having a hydroxyl group or a hydroxymethyl group as a substituent, and a furyl group having a hydroxyl group or a hydroxymethyl group as a substituent. Alternatively, an ozonide reducing agent showing a pyridyl group having a hydroxyl group or a hydroxymethyl group as a substituent can be preferably exemplified.

Specific examples of the ozonide reducing agent represented by the above general formula (2) include, for example, bis (hydroxyheterocyclic) sulfide derivatives [more specifically, thiodihydroxythiophene, thiodihydroxymethylthiophene, thiodihydroxyfuran] Thiodihydroxymethylfuran, thiodihydroxypyridine, thiodihydroxymethylpyridine and the like]. They are,
One type is used alone, or two or more types are used in combination.

Further, the compound of the general formula (1) and the compound of the general formula (2) can be used in combination.

As starting materials for the ozonolysis reaction to which the present invention can be applied, a new experimental chemistry course, Vol.
2] Chapter 10 (issued year; September 20, 1975, publisher;
Alkenes, as described in Maruzen Co., Ltd.)
Alkynes, aromatic compounds, including heterocyclic aromatic compounds, include all organic compounds having a carbon-carbon or carbon-nitrogen unsaturated bond in the molecule, specific examples thereof include substituted ethylenes, There are steroids, enol ethers, azines, diazoalkanes, Schiff bases and the like. More specifically, indene, styrene, cyclohexene, cyclohexylidene, camphene, longiolefin, norbornene, naphthoquinone, vinylcyclohexene, α-binene , Benzene, naphthalene, phenanthrene, anthracene, phenol, quinoline, pyrrole, furan, thiophene, indole, benzofuran,
Examples include diphenylethyl carbinol, nitrone, acetal and the like. Furthermore, the ozonide reducing agent of the present invention can be applied to a β-lactam compound having an unsaturated bond in a side chain by handling near neutrality, and is specifically described in JP-A-2-306973. It can be used for bicyclic oxazolinoazetidinone derivatives, thiazolinoazetidinone derivatives, monocyclic azetidinone derivatives, exomethylene cephem derivatives, exomethylene penum derivatives, etc.

As the reaction conditions for the ozonation reaction, for example, Chapter 15 of the New Experimental Chemistry Course [I-2] Chapter 10 (published year;
The conditions described in September 20, 1975, published by Maruzen Co., Ltd.) can be widely applied. Specifically, the ozonation reaction is performed in a suitable solvent. Solvents that can be used include, for example, alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, methyl formate, ethyl formate,
Propyl formate, butyl formate, methyl acetate, ethyl acetate,
Lower alkyl esters of lower carboxylic acids such as propyl acetate, butyl acetate, methyl propionate, and ethyl propionate; acetone, methyl ethyl ketone, methyl propyl ketone, methyl butyl ketone, methyl isobutyl ketone, ketones such as diethyl ketone, diethyl ether,
Ethyl propyl ether, ethyl butyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, ethers such as methyl cellosolve, dimethoxyethane, tetrahydrofuran, dioxane, cyclic ethers such as 1,3-dioxolan, acetonitrile, propionitrile, butyronitrile, Isobutyronitrile,
Nitriles such as valeronitrile, benzene, toluene,
Xylene, chlorobenzene, substituted or unsubstituted aromatic hydrocarbons such as anisole, dichloromethane, chloroform, dichloroethane, trichloroethane, dibromoethane, propylene dichloride, carbon tetrachloride, halogenated hydrocarbons such as freons, pentane, hexane, Examples thereof include aliphatic hydrocarbons such as heptane and octane, cycloalkanes such as cyclopentane, cyclohexane, cycloheptane and cyclooctane, amides such as dimethylformamide and dimethylacetamide, and dimethylsulfoxide. These may be used alone or as a mixture of two or more. Further, these organic solvents may contain water as necessary.

These solvents are usually used in an amount of about 1 liter to 200 liters, preferably about 2 liters to 100 liters, per 1 kg of the starting material.
The reaction temperature of the above reaction is usually about -78C to 40C, preferably about -60C to 10C. The amount of ozone used in the above reaction is usually 1 equivalent to the above-mentioned starting material, but if necessary, it is better to pass ozone until the starting material is further consumed. When the amount of ozone used exceeds 1 equivalent, it is preferable to drive off excess ozone by passing dry nitrogen into the reaction mixture, and then perform post-treatment.

The reduction treatment of the ozonized product (ozonide) of the present invention is carried out by directly adding the ozonide reducing agent of the present invention to the above-mentioned ozonation reaction solution. The amount used is at least 1 equivalent or more, preferably about 1 to 3 equivalents, based on the starting material to be subjected to the ozonolysis reaction described above.

The ozonide reduction step of the present invention is usually carried out at -76.
C. to 100 C., preferably -40 C. to 30 C.
It is preferred to carry out in the temperature range described above. When the treatment temperature is high, the risk of explosion increases and the yield tends to decrease,
Conversely, when the treatment temperature is low, the reduction reaction rate is reduced, and a greater amount of the reducing agent tends to be required. The processing time is usually about 3 minutes to 12 hours, preferably about 30 minutes to 6 hours.

In the post-treatment after the reduction step, sulfoxide, which is an oxidized form of the ozonide reducing agent of the present invention, is a water-soluble and highly crystalline compound, and can be easily removed from the reaction system by washing or filtration. By subjecting the reaction solution to a concentration operation and a crystallization operation, the target product can be obtained as a substantially pure product, but it can be naturally purified by other methods. Further, the sulfoxide of the ozonide reducing agent generated here can be incinerated.

[0037]

The ozonide reducing agent of the present invention dissolves in all kinds of solvents (aqueous, non-aqueous, polar and non-polar) and maintains a uniform state at a wide range of temperatures (-76 ° C to 40 ° C). It is a compound that is less subject to use restrictions,
Wastewater regulations are not as strict as phosphorus compounds, and there is less odor peculiar to sulfur compounds, so special equipment for environmental measures is not required.

Further, due to the easily oxidizable property found in the two-coordinate sulfur compound, the yield of the target substance is improved under mild conditions, handling as a dangerous substance is easy, and there is little risk of explosion.

After further treatment, the ozonide reducing agent itself becomes a sulfoxide, which can be easily removed by washing with water in an organic solvent, and does not adversely affect the subsequent steps. In addition, the removed sulfoxide can be incinerated, for example, as compared with the above-mentioned ozonide reducing agent in the conventional ozonolysis reaction.
It is a compound with many excellent features.

[0040]

EXAMPLES Next, the present invention will be described in more detail with reference to working examples of the ozonide reducing agent of the present invention as working examples, but the present invention is not limited to these working examples.

Example 1 p-methoxybenzyl 2- (4-benzenesulfonylthio-3-phenylacetamido-2-azetidinone-
Preparation of 1-yl) -3-hydroxy-2-butenoate 2 p-methoxybenzyl 2- (4-benzenesulfonylthio-3-phenylacetamido-2-azetidinone-
1-yl) -3-methyl-3-butenoate 1 193 g
(Purity 97.3%, 315.5 mmol), 1000 ml of methylene chloride and 75 ml of isopropyl alcohol are added and dissolved by stirring. The reaction solution was cooled to -15 ° C, and ozone gas ( ₃ gO ₃ / hr) was introduced at -20 ° C to 15 ° C over 5 hours and 30 minutes. Excessive ozone gas was removed with nitrogen gas, thiodiethanol (40 ml) was added at -10 ° C, and the mixture was stirred for 12 hours while the temperature was raised to room temperature. The reaction solution was filtered to remove the precipitated thiodiethanol sulfoxide, and then the organic layer was concentrated under reduced pressure. 1200 ml of 10% aqueous isopropyl alcohol is added to the residue, and the mixture is cooled to 24 ° C. or lower for crystallization. Furthermore, 440m of water
The crystals are squeezed out by adding 1 and aged at 10 ° C. for 1 hour. Filtered off the crystals, water-containing isopropyl alcohol, then washed with cold isopropyl alcohol, and dried to give the title compound crystal 2 186.3G (purity 98%) in 97% yield. The ¹ H-NMR spectrum of this product was consistent with that of the standard.

[0042]

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Example 2 Diphenylmethyl 2- (4-benzenesulfonylthio-3-phenylacetamido-2-azetidinone-1-
Preparation of yl) -3-hydroxy-2-butenoate 4 diphenylmethyl 2- (4-benzenesulfonylthio-3-phenylacetamido-2-azetidinone-1-
Yl) -3-methyl- 3 -butenoate 3 211 g
(Purity: 98.2%, 323.2 mmol), 1000 ml of methylene chloride and 75 ml of isopropyl alcohol are added and dissolved by stirring. The reaction solution was cooled to −15 ° C., and ozone gas ( ₃ gO ₃ / hr) was added at −20 ° C. to −15 ° C. for 5 minutes.
Introduced over a period of 30 minutes. Excessive ozone gas is removed with nitrogen gas, and thiodiethanol 40 m
l, and the mixture was stirred for 12 hours while the temperature was raised to room temperature. The thiodiethanol sulfoxide was removed from the reaction solution by washing with 400 ml of water, and then the organic layer was concentrated under reduced pressure. 1200 ml of 10% aqueous isopropyl alcohol is added to the residue, and the mixture is cooled to 24 ° C. or lower for crystallization. Further, 440 ml of water is added thereto to squeeze out the crystals, and the mixture is aged at 10 ° C. for 1 hour. The crystals were collected by filtration, washed with aqueous isopropyl alcohol, then with cold isopropyl alcohol, and dried to give the title compound crystal 4.
201.4 g (purity 98%) was obtained in a yield of 95%. The ¹ H-NMR spectrum of this product was consistent with that of the standard.

[0044]

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Examples 3 to 12 The reaction was carried out under the same reaction conditions as in Example 1 except that the reaction was carried out at the reaction temperature shown in Table 1 using the ozonide reducing agent and the solvent shown in Table 1. The alcohol body 2 was obtained. Table 1 shows the results of these reactions.

[0046]

[Table 1]

Examples 13 to 18 The reaction was carried out under the same reaction conditions as in Example 2 except that the reaction was carried out using the solvents shown in Table 2 at the reaction temperatures shown in the same table, and the desired alcohol 4 was obtained. Obtained. Table 2 shows the results of these reactions.

[0048]

[Table 2]

Example 19 Diphenylmethyl 1- (3-benzyl-2-thia-
Preparation of 4,7-diazabicyclo [3.2.0] hept-3-en-6-one-7-yl) -3-hydroxy-2-butenoate 6 diphenylmethyl 1- (3- Benzyl-2-thia-
4,7-diazabicyclo [3.2.0] hept-3-en-6-one-7-yl) -3-methyl-3-butenoate 5 250 g of methylene chloride and 25 ml of isopropyl alcohol in 50 g And dissolve with stirring. The reaction solution was
After cooling to 15 ° C., ozone gas was introduced for 1 hour and 40 minutes. Remove excess ozone gas with nitrogen gas,
At -10 ° C, 11 ml of thiodiethanol and 12 ml of thiodipropionitrile were added, and the mixture was returned to room temperature and stirred for 3 hours. The reaction solution was filtered to remove the precipitated thiodiethanol sulfoxide, and 200 ml of 5% aqueous sodium bicarbonate solution was added.
And washed with water 100ml2 times, dried over anhydrous magnesium sulfate to give the title compound 6 40 g concentrated under reduced pressure. The ¹ H-NMR spectrum of this product was consistent with that of the standard.

[0050]

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Example 20 p-Nitrobenzyl 1- (4-formyl-3- (4-
Nitrophthalimide) -2-azetidinone-1-yl)
Preparation of -3-hydroxy-2-butenoate 8 p-nitrobenzyl 1- (4-formyl-3- (4-
Nitrophthalimide) -2-azetidinone-1-yl)
100 ml of methylene chloride and 7.5 ml of isopropyl alcohol were added to 20.1 g of -3-methyl-3-butenoate 7.
ml was added and suspended. The reaction solution was cooled to −15 ° C., and ozone gas was introduced for 30 minutes. After purging excess ozone with nitrogen gas, 6.2 ml of thiodiethanol was added, and the mixture was stirred for 1.5 hours while returning to room temperature. The reaction solution was washed once with 200 ml of 5% aqueous sodium bicarbonate and twice with 200 ml of water, dried over anhydrous magnesium sulfate, and powdered with 500 ml of isopropyl ether to obtain 15 g of the title compound.
Obtained. The ¹ H-NMR spectrum of this product was consistent with that of the standard.

[0052]

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EXAMPLE 21 Preparation of 1- (4-methoxyphenyl) azetidin-2,3-dione 10 1- (4-methoxyphenyl) 3-methyleneazetidin-2-one 9 100 ml of methylene and 7.5 ml of isopropyl alcohol are added and dissolved by stirring. The reaction solution was cooled to −15 ° C., and ozone gas was introduced over 30 minutes. After that, excess ozone gas was removed with nitrogen gas, and thiodiethanol 3 ml at −10 ° C.
And 6 g of thiodicresol were added, and the mixture was returned to room temperature and stirred for 1 hour. The reaction solution was filtered to remove the precipitated thiodiethanol sulfoxide, and 5% aqueous sodium hydrogen carbonate was added.
washed with ml of water 50ml2 times, dried over anhydrous magnesium sulfate to give the title compound 10 14 g concentrated under reduced pressure. The ¹ H-NMR spectrum of this product was consistent with that of the standard.

[0054]

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Examples 22 to 39 Tables 3 to 8 show the reaction conditions and results of the ozonolysis reaction performed using the reducing agent and the starting material represented by the following structural formulas.

[0056]

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[0057]

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[0058]

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[0059]

[Table 3]

[0060]

[Table 4]

[0061]

[Table 5]

[0062]

[Table 6]

[0063]

[Table 7]

[0064]

[Table 8]

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-2-306973 (JP, A) JP-A-55-120538 (JP, A) JP-A-47-18814 (JP, A) Edited by The Chemical Society of Japan, "New Experimental Chemistry, Vol. 15, Oxidation and Reduction (I) -2", Maruzen Co., Ltd., September 20, 1976, p. 563-p. 603 (58) Field surveyed (Int. Cl. ⁷ , DB name) C07B 31/00

Claims (8)

(57) [Claims] An ozonide reducing agent used for reductive decomposition treatment of ozonide is a hydroxyl group, a nitrile group or a carboxylic acid.
An ozonide reducing agent, which is a compound having a hydrocarbon residue substituted with a ruboxyl group at both ends of sulfur. Wherein ozonide reducing agent of the general formula ^{X-R 1 -R 2 -S-} R 3 -R 4 -Y (1) [wherein, R ¹ and R ⁴ are the same or different, single bond Or
Shows an aliphatic hydrocarbon residue. R ² and R ³ are the same or different
Is a saturated or unsaturated aliphatic hydrocarbon residue,
It represents a cyclic hydrocarbon residue or an aromatic hydrocarbon residue. X and
And Y are the same or different and each represents a hydroxyl group, a nitrile group,
Represents a ruboxyl group. And a compound represented by the general formula R ⁵ -SR ⁶ (2) wherein R ⁵ and R ⁶ are the same or different and each represents a substituent.
Hydroxyl, hydroxymethyl, nitrile, cyanome
Group consisting of tyl group, carboxyl group and carboxymethyl group
Represents a heterocyclic group having at least one group selected from
You. ] Selected from the group consisting of compounds represented by
The ozonide reducing agent according to claim 1, which is at least one compound . 3. ozonide reducing agent of the general formula ^{X-R 1 -R 2 -S-} R 3 -R 4 -Y (1) [wherein, R ¹ and R ⁴ are the same or different, single bond Or
Shows an aliphatic hydrocarbon residue. R ² and R ³ are the same or different
Is a saturated or unsaturated aliphatic hydrocarbon residue,
It represents a cyclic hydrocarbon residue or an aromatic hydrocarbon residue. X and
And Y are the same or different and each represents a hydroxyl group, a nitrile group,
Represents a ruboxyl group. ] The compound represented by the formula:
Item 3. An ozonide reducing agent according to item 2. 4. An ozonide reducing agent wherein R ¹ and R ⁴ are the same or different.
Different single bond or linear or branched C _1-6 alkyl
And R ² and R ³ are the same or different and are linear or
A branched C _1-6 alkylene group, a linear or branched
Alkenylene group C _2-8, straight or branched authors C _2-6
Lucinylene group, C _3-8 cycloalkylene group or phenyl
A C _1-6 alkyl group and / or an amino group are substituted on the
Indicates a phenylene group which may have, X and Y are the same or
Shows hydroxyl group, nitrile group or carboxyl group differently
The ozonide according to claim 3, which is a compound of the general formula (1).
Reducing agent. 5. An ozonide reducing agent wherein R ¹ and R ⁴ are both single bonds
R ² and R ³ are both linear C _1-6 alkyl
X and Y each represent a hydroxyl group or a nitrile group.
The ozonide compound according to claim 4, which is a compound of the general formula (1).
Base agent. 6. The ozonide reducing agent is thiodiethanol,
Odipropanol, thiodiisopropanol, thiodic
Resole, thiodipropionitrile, thiodipropion
Acid, thiodiphenol and thiodi (2-methylphenol
At least one compound selected from the group consisting of
An ozonide reducing agent according to claim 4. 7. An ozonide reducing agent wherein R ⁵ and R ⁶ are both substituted
Having a hydroxyl group or a hydroxymethyl group
Enyl group, hydroxyl group or hydroxymethyl
A hydroxyl group or a furyl group having a
General formula showing a pyridyl group having a hydroxymethyl group
The ozonide reduction according to claim 2, which is a compound of (2).
Agent. 8. A method for reducing ozonide, comprising adding the ozonide reducing agent according to claim 1 to a reaction system in the reductive decomposition treatment of ozonide.