JPH0535151B2 - - Google Patents

Description

[Detailed description of the invention] Industrial application field The present invention is based on the formula It relates to 2,2-dimethyl-1,3-oxathian-3,3-dioxide [hereinafter referred to as sulfone ()] shown by The sulfone () provided by the present invention synthesizes natural physiologically active substances or their analogs that are important as fragrances such as diasmones, pesticides such as insect pheromones and insect hormones, and pharmaceuticals such as prostaglandins and steroids. General formula useful as an intermediate for (In the formula, R represents an alkyl group, an alkenyl group, a cycloalkyl group, an aralkyl group or an aryl group) [hereinafter,
This is useful as a raw material for the synthesis of hydroxyketone (referred to as hydroxyketone). BACKGROUND ART Although sulfone () is a new compound that has not been described in any literature, several methods for synthesizing hydroxyketone () derived from this compound and its ester are known. For example, Yoshioka et al. report in Pharmaceutical Journal, Vol. 93, pp. 1183-1187, that by acid-treating α-acyl-γ-butyrolactone obtained by condensation of γ-butyrolactone and an ester, R is an isobutyl group in the general formula (). reported the synthesis of hydroxyketones with propyl or benzyl groups. M. Larcheveque et al. Synthesis, 1975, 256
259, it is reported that a hydroxyketone in which R is an isobutyl group or a hexyl group in the general formula () was synthesized by treating with a ketimine basic compound and reacting the generated anion with oxirane. H.C.Brown et al. J.Am.Chem.Soc., vol. 89, 4530
-4531, it is reported that by reacting dicyclohexylborane and allyl benzoate and carbonylating the resulting trialkylborane, a benzoic acid ester of a hydroxyketone in which R is a cyclohexyl group in the general formula () was obtained. There is. P.J. Wagner et al. J.Am.Chem.Soc., vol. 94, 7495~
Friedel succinic anhydride in benzene on page 7499
-Crafts reaction, esterify the resulting β-benzoylpropionic acid, protect its carbonyl group with a ketal, reduce the ester moiety, and then remove the ketal. reported the synthesis of hydroxyketones in which R is a phenyl group. In addition, the general formula that is considered to be equivalent to hydroxyketone () in terms of organic synthesis chemistry A method for synthesizing a γ-haloketone (hereinafter referred to as haloketone ( )) represented by the formula (wherein R is as defined above and X represents a halogen atom) is also known. For example, JBBicking et al. J.Med.Chem., vol. 20,
On pages 35 to 43, by reacting 4-chlorobutyronitrile with a Grignard reagent prepared from 1-bromopentane, in the general formula (), R is an n-heptyl group and X is a chlorine atom. reported that they had synthesized a haloketone. Problems to be Solved by the Invention In the method of Yoshioka et al., the final step is an acid treatment step using 10% hydrochloric acid, and considering that hydroxyketone () is unstable to acids, the yield is good. It is difficult to predict the yield, and their report does not mention the yield. According to the method of M. Larcheveque et al., hydroxyketones () are obtained in good yields, but in order to synthesize hydroxyketones () with different alkyl groups, ketimines with corresponding alkyl groups are required. , it is not possible to easily synthesize many types of hydroxyketones () with different alkyl groups. Similarly, in the method of H.C.Brown et al., in order to synthesize hydroxyketones () with different alkyl groups, it is necessary to use dialkylborane having the corresponding alkyl group as the starting material, and the isolation yield is not very good. . In the paper, the method of PJ Wagner et al. is limited to the synthesis of hydroxyketones () in which R is represented by a phenyl group, but for example, when synthesizing hydroxyketones () in which R is represented by an alkyl group, the general formula (In the formula, R is as defined above.) [Hereinafter, this will be referred to as a ketoester (). ] is considered as an intermediate, this method can also be applied as a method for synthesizing hydroxyketone () in which R is an alkyl group. However, this method requires a large number of steps, and the reaction of protecting the ketone of a compound that has a ketone and an ester in the same molecule, such as ketoester (), by converting it into ethylene ketal generally reduces the yield due to side reactions such as transesterification. It cannot be said to be an excellent method, considering that it is known to be harmful and that the final step, the deketalization reaction using an acid, is also considered to be harsh on the product hydroxyketone (). Furthermore, the method of JBBicking et al. for obtaining haloketone () has a problem in that the Grignard reaction proceeds only at a rate of 20 to 30%. As described above, all of the synthesis methods known in the literature for hydroxyketones () or haloketones () have the problems shown above, and hydroxyketones () or haloketones () with different alkyl groups
Currently, there is a desire to develop a method that enables production on an industrial scale. Therefore, the object of the present invention is to provide a method for producing hydroxyketone (), which is a synthetic intermediate for useful substances such as fragrances, agricultural chemicals, and medicines, on an industrial scale and in good yield.
The purpose of this invention is to provide a novel synthetic intermediate. Means for Solving the Problems According to the present invention, the above object is achieved by providing a sulfone represented by the general formula (). The alkyl group represented by R in the above general formula () is methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, pentyl group, isopentyl group, neopentyl group, hexyl group, heptyl group. groups, octyl groups, etc.
Alkenyl groups include 3-cis-hexenyl, cycloalkyl groups include cyclopentyl and cyclohexyl, aralkyl groups include benzyl, and aryl groups include phenyl, tolyl, xylyl, and naphthyl groups. Illustrated. The sulfone () of the present invention has a formula known in the literature. 2,2-dimethyl-1,3-oxathiane (hereinafter referred to as oxathiane).
B. Sjoberg, Ber., 75B , 13-29 (1942)].
This oxidation usually oxidizes the reaction system by using peroxides such as hydrogen peroxide, peracids, potassium permanganate, and sodium metaperiodate, among the many reagents known to oxidize sulfides to sulfones. It is preferable to use an oxidizing agent that can maintain neutrality [see New Experimental Chemistry Course, Synthesis and Reaction of Organic Compounds (), pp. 1759-1761, Maruzen (1978)]. The amount of oxidizing agent is oxathian ()
It is sufficient if the amount is 2 equivalents or more, but usually about 2 to 3 equivalents are used. For example, when a peracid such as peracetic acid or metachloroperbenzoic acid is used as the oxidizing agent, as the reaction progresses, acids such as acetic acid and metachlorobenzoic acid are liberated, respectively. Since oxathiane () is unstable to acids, it is preferable to add a basic substance such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, etc. to the reaction system to neutralize the generated acid.
The basic substance may be used in an excess amount of 2 equivalents or more relative to oxathian (), but preferably 3 to 4 equivalents. It is usually preferable to carry out this reaction in a solvent. As the solvent, water and hydrophilic solvents such as methanol, ethanol, and acetone can be used alone or in combination.
Furthermore, a halogenated hydrocarbon solvent such as methylene chloride or chloroform can be added to water and these hydrophilic solvents. The amount of solvent to be used is not critical, but it is about 1 to 1000 times the weight of oxathian (2000), preferably 3 to 500 times the weight of oxathian (). The reaction temperature ranges from 0°C to the boiling point of the solvent used, preferably from 10°C to 30°C. The reaction time depends on the reaction temperature used, but is usually
The reaction time is about 10 minutes to 10 hours, and it is convenient to follow the progress of the reaction by thin layer chromatography and to conclude the reaction when the spots originating from the raw materials disappear. After completion of the reaction, isolation and purification of the product from the reaction mixture are carried out in accordance with methods used for isolation and purification of products obtained by general organic synthesis reactions from the reaction mixture. For example, if a hydrophilic solvent is used, the solvent is distilled off under reduced pressure if necessary, water is added to the residue, and a solvent such as ether or ethyl acetate or a halogenated hydrocarbon solvent such as methylene chloride or chloroform is added. Extract using Separate the organic layer and extract the aqueous layer well with solvent. The organic layers are combined, washed with brine, dried with a desiccant such as anhydrous magnesium sulfate or anhydrous sodium sulfate, and then the solvent is distilled off under reduced pressure. The residue was reconsolidated from a mixed solvent of methylene chloride and hexane,
Get sulfone (). The conversion of sulfone ( ) to hydroxyketone ( ) provided by the present invention is carried out as follows. (In the above formula, R is as defined above.) That is, after treating the sulfone () with a basic compound, it is reacted with an aldehyde represented by the general formula () [hereinafter referred to as aldehyde ()]. After oxidizing the resulting sulfone alcohol represented by the general formula () [hereinafter referred to as sulfone alcohol ()], hydroxyketone () is obtained by treating with hydrous silica gel. The reaction between sulfone () and aldehyde () is usually carried out in an ethereal solvent such as tetrahydrofuran or 1,2-dimethoxyethane under an inert gas atmosphere such as nitrogen or argon. Treatment with basic compounds such as organolithium reagents such as lithium, alkali metal hydrides such as sodium hydride, lithium hydride, etc. This is carried out by generating an anion represented by [hereinafter referred to as anion ()] and adding aldehyde () to this anion solution. The amount of solvent used to generate the anion () is not critical, but it is approximately
500 times the weight, preferably about 10 to 100 times the weight.
The reaction temperature is in the range of -100°C to room temperature, preferably in the range of -78°C to 0°C, more preferably in the range of -78°C to
-30℃ range. The reaction time depends on the reaction temperature used, but is usually about 1 minute to 30 minutes. The amount of basic compound used is 0.9 to 1.2 to sulfone ()
equivalent, preferably 1.0 to 1.1 equivalent. When adding the aldehyde () to the anion () produced in this way, the aldehyde () can be added dropwise as it is or a solution diluted with the solvent used to generate the anion ().
This reaction is also in the range of -100°C to room temperature, preferably -78°C to
The reaction is carried out at a temperature in the range of 0°C, more preferably in the range of -78°C to -30°C, and for a reaction time of about 1 minute to 30 minutes. Isolation and purification of the product from the reaction mixture are carried out in the same manner as those used for the isolation and purification of products obtained by general organic synthesis reactions from the reaction mixture. For example, after distilling off the solvent under reduced pressure if necessary, water is added and extraction is performed with a solvent such as ether or ethyl acetate or a halogenated hydrocarbon solvent such as methylene chloride or chloroform.
Separate the organic layer and thoroughly extract the aqueous layer with a solvent. The organic layers are combined, washed with brine, dried with a desiccant such as anhydrous magnesium sulfate or anhydrous sodium sulfate, and the solvent is distilled off under reduced pressure to obtain a crude product of sulfonic alcohol (2). This crude product can also be purified by operations such as column chromatography. Next, the conversion of sulfone alcohol () to hydroxyketone () starts by first subjecting sulfone alcohol () to an oxidation reaction. As the oxidizing agent used here, various oxidizing agents known to normally oxidize alcohol to carbonyl groups can be used [New Experimental Chemistry Course, Oxidation and Reduction [-1], [-2], See Maruzen (1976)].
Due to the ease of reaction operation, chromic acid,
Preferably, the Jones oxidation reaction using sulfuric acid is employed. The amount of acetone used is about 10 to 200 times the weight of sulfone alcohol (2018). Jones
Theoretically, the amount of the reagent may be 1 equivalent relative to the sulfonic alcohol (), but it is usually used in a slight excess.
The reaction temperature is around 0°C, and the reaction time is within 30 minutes. Normally, the Jones reagent is added dropwise little by little, and if the Jones reagent becomes excessive relative to the sulfonic alcohol (), the red color of the Jones reagent will not disappear, so after confirming the disappearance of the raw material by thin layer chromatography, immediately Post-treatment of the reaction is preferred. For post-treatment of the reaction, first, isopropanol is added dropwise to the reaction mixture until the red color of the Jones reagent disappears to decompose the excess Jones reagent.
After adding water, extraction is performed with a solvent such as ether or ethyl acetate, or a halogenated hydrocarbon solvent such as methylene chloride or chloroform. Separate the organic layer and extract the aqueous layer with a solvent. The organic layers were combined, washed with brine, dried using a desiccant such as anhydrous magnesium sulfate or anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. A crude product of ketosulfone (hereinafter referred to as ketosulfone ( )) represented by the formula (wherein R is as defined above) is obtained. Without purifying this ketosulfone (), it is diluted with a solution of solvents such as hexane, ether, and ethyl acetate alone or in a mixture, and adsorbed onto silica gel that has been inactivated by adding a small amount of water in advance. Add water and let stand or stir overnight. The obtained silica gel adsorbate is placed on the top of a freshly prepared silica gel column and purified by chromatography to obtain hydroxyketone (). Further, when converting sulfone () to hydroxyketone (), the following alternative method can also be used. (In the formula, R is as defined above, and R ² represents a lower alkyl group.) That is, the general formula ( ) (hereinafter referred to as ester ()) directly produces a ketosulfone represented by the general formula (). Hydroxyketone () is obtained by treating this ketosulfone () by the method described above. Various conditions during the reaction between anion () and ester () and ketosulfone () from the reaction mixture after the reaction is complete
The isolation method can be carried out in the same manner as in the various conditions used in the reaction between the anion () and the aldehyde () and the method used to isolate the sulfonic alcohol from the reaction mixture. The conversion of ketosulfone ( ) to hydroxyketone ( ) is as described above. The hydroxyketone () thus obtained can be easily converted into a haloketone (). For example, by treating with thionyl chloride in the presence of pyridine, triethylamine, etc., a haloketone in which X in the general formula () is a chloro group can be obtained. Hydroxyketone () or Haloketone ()
can be converted into fragrances, pesticides, medicines, etc. For example, in the general formula (), R is 3-cis-
Hydroxyketone represented by a hexenyl group can be converted to cis-diasmone, a fragrance, by the following route. In the above formula, the conversion of dienone (XI) to cis-diasmone has already been reported by PAGrieco [J.Org.Chem., 37, 2363-2364 (1972)
reference〕. In exactly the same way, dihydrdiasmone can be synthesized from a hydroxyketone in which R is a hexyl group in the general formula (). Furthermore, this method for synthesizing the cyclopentenone skeleton can also be applied to the synthesis of prostaglandins. Chalcogran, which is the main aggregation pheromone of Pityogenes Chalcographus (L), an insect that damages forests in Europe, can be synthesized from hydroxyketone in which R is an ethyl group in the general formula (). In the general formula (), R is n-heptyl group and induced by 11,12-secoprostaglandins, which exhibit the ability to enhance [JBBicking et al., J.Med.Chem., 20 , 35~
43 (1977)] In the general formula (), R is a methyl group,
A haloketone in which X is a chlorine atom or an iodine atom is used as a raw material for a structural unit in the synthesis of juvenile hormone. [In the above formula, R ¹ represents a methyl group or an ethyl group.
Ph represents a phenyl group. JAFindlay et al.
J. Chem, Soc, (C), 1970 , 2631-2635] In the general formula (), R is a methyl group and Used as raw material for Crignard reagent during synthesis. [In the above formula, Ph represents a phenyl group and Py represents pyridine. L.Velluz et al., CRAcadl.Sci., Paris;
257, 3086 (1963)] [Examples] Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples. In addition, in the examples and reference examples,
Infrared absorption spectroscopy (IR analysis) is measured in CHCl ₃ solution, nuclear magnetic resonance spectroscopy (NMR
Analysis) was measured using tetramethylsilane (TMS) as an internal standard and _CDCl3 as a solvent. Example 1 13.2 g of oxathian () was dissolved in 1 part of methylene chloride, 500 ml of an aqueous sodium carbonate solution was added to form two layers, and 44 g of 80% metachloroperbenzoic acid was gradually added while stirring at room temperature. After the addition was complete, stirring was continued for an additional 30 minutes at room temperature. Transfer the reaction solution to a separatory funnel, separate the liquids, separate the organic layer, and remove the aqueous layer.
Extracted twice with 250 ml of methylene chloride. The organic layers were combined, washed with brine, and then dried using anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was recrystallized using a mixed solvent of methylene chloride and hexane to obtain 11 g (67%) of sulfone (). mp 63-65℃ IR analysis: 1305, 1290, 1105, 1075 cm ^{-1 1} H-NMR analysis δ ^ppm _CDCl3 : 1.64 (6H, s, C( CH
₃ ) ₂ , 2.32 (2H, m, _-CH2 - CH2 _{- CH2-} ),
3.22 (2H, t, J=6Hz, -CH2 _- O-), 3.90
(2H, t, J=6Hz, -CH2 - _SO2- ) Elemental analysis: Actual value C, _43.73 : H, 7.12 Calculated value C, 43.88: H, 7.37 MS analysis: 165 [M+1] Example 2 13.2 After adding 22.8 g of 30% hydrogen peroxide solution to g of oxathian () and stirring at room temperature for 1 hour,
Stirring was continued under heating and reflux for 4 hours. After cooling, the reaction mixture was diluted with approximately 100 ml of water and extracted three times with 100 ml of methylene chloride. The organic layers were combined, washed with brine, and then dried using anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, it was recrystallized using a mixed solvent of methylene chloride and hexane, yielding 10.5 g (64%).
The sulfone () was obtained. The melting point and various analysis results of this product were completely consistent with those obtained in Example 1. Reference Example 1 8.49 g of sulfone () was dissolved in 500 ml of tetrahydrofuran, cooled to -78°C, and 1.1 equivalents of n-butyllithium solution was gradually added dropwise with stirring under a nitrogen atmosphere to generate anion (). Ta. After continuing stirring at −78° C. for 10 minutes, 7.8 g of an aldehyde of the general formula () in which R is an n-heptyl group was gradually added dropwise. After the addition was completed, stirring was continued for another 10 minutes, and disappearance of the raw material was confirmed by thin layer chromatography. After about 1 ml of water was added to the reaction mixture, the cooling bath was removed and the mixture was stirred for a while at room temperature. The solvent was distilled off under reduced pressure, and about 100 ml of water was added to the resulting residue, which was extracted three times with 100 ml of methylene chloride. The organic layers were combined, washed with brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting concentrate was subjected to silica gel column chromatography using methylene chloride to obtain 11.8 (8.6%) of the product. According to the analysis results below, this product has a general formula () in which R is n-
It was confirmed that it was a sulfone alcohol with a heptyl group. In addition, the result of recrystallization mp is 50-51
It was warm at ℃. IR analysis: 3540, 3010, 2950, 2925, 1295, 1210,
1100, 1075cm ^{-1 1} H-NMR analysis δ ^ppm _CDCl3 0.88 (3H, t), 1.55
1.1-3.0 including (3H, s) and 1.72 (3H, s)
(17H), 3.16 (1H, ddd, J = 1.5Hz, 4Hz, 13
Hz), 3.93 (1H, d, J=2Hz), 4.02 (1H, t,
J=2Hz), 4.44-4.68 (1H, bd) Elemental analysis: Actual value C, 54.44: H, 8.82 Calculated value C, 54.21: H, 9.15 Reference example 2 In the general formula () used in Reference example 1, R is The same procedure as in Reference Example 1 was carried out except that 8.7 g of aldehyde in which R in the general formula () is a cyclohexyl group was used instead of 7.8 g of aldehyde which is a heptyl group, and a general 11.5 g (80%) of a sulfonic alcohol in which R is a cyclohexyl group in formula () was obtained. IR analysis: 3530, 2920, 2850, 1295, 1280, 1100,
1075cm ^{-1 1} H-NMR analysis δ ^ppm _CDCl3 : 1.56(s), 1.72(s), 1.73(s)
Including 0.8~3.2 (20H), 3.24~3.64 (1H, m),
3.93 (1H, m), 4.02 (1H, m), 4.20 (1H, bd) Elemental analysis: Actual value C, 56.46; H, 8.52 Calculated value C, 56.49; H, 8.75 Reference example 3 Used in Reference example 1 The same operation as in Reference Example 1 was carried out except that 5.6 g of an aldehyde in which R is an isopropyl group in the general formula () was used instead of 7.8 g of an aldehyde in which R in the general formula () is a heptyl group. 9.1 g (74%) of a sulfonic alcohol having the general formula () in which R is an isopropyl group and having the following analytical results was obtained. IR analysis: 3550, 3020, 2950, 1295, 1210, 1100,
1075cm ^{-1 1} H-NMR analysis δ ^ppm _CDCl3 : 0.88 to 1.16 (6H, m, (C
H ₃ ) ₂ CH), 1.5 including 1.56(s), 1.74(s), 1.76(s)
~3.05 (10H), 3.16 (1H, m) 3.80 ~ 4.20 (3H) Elemental analysis: Actual value C, 50.41; H, 8.28 Calculated value C, 50.82; H, 8.53 Reference example 4 General formula used in Reference example 1 The same operation as in Reference Example 1 was performed except that 8.3 g of an aldehyde in which R is a phenyl group in the general formula () was used in place of 7.8 g of an aldehyde in which R is a heptyl group in (), and mp123.5-125℃ as well as the main component of
9.5 g (68%) of a sulfone alcohol having a general formula () in which R is a phenyl group was obtained as a mixture of diastereomers with a temperature of mp 123.5 to 125°C. The results of each analysis are shown below. (i) Principal component IR analysis: 3520, 3015, 1600, 1295, 1210,
1100, 1070, 1050, 695 cm ^{-1 1} H-NMR analysis: 1.59 (3H, s), 1.72 (3H,
s), 1.75 (1H, m), 2.47-3.00 (2H, m)
3.30 (1H, ddd, J=2Hz, 4Hz, 13Hz),
3.81 (1H, t, J = 1.5Hz), 3.90 (1H, d,
J=2Hz), 5.78 (1H, br., s), 7.24~8.00
(5H, m) Elemental analysis: Actual value C, 57.44; H, 6.87 Calculated value C, 57.76; H, 6.71 (ii) Diastereomer IR analysis: 3530, 3020, 1600, 1290, 1275,
1210, 1100, 1070, 695cm ^{-1 1} H-NMR analysis: 1.08-1.40 (1H, m), 1.60
(3H, s), 1.78 (3H, s), 1.80~2.32 (1H,
m), 3.1-4.2 (4H), 5.28 (1H, d, J=6
Hz), 7.35 (5H, s) Elemental analysis: Actual value C, 57.27: H, 6.63 Calculated value C, 57.76: H, 6.71 Reference example 5 2.7 g of 50% oily sodium hydride was suspended in 500 ml of tetrahydrofuran, After cooling to −30°C and stirring under nitrogen atmosphere, 8.49 g of sulfone ()
was gradually added dropwise. After the addition was completed, stirring was continued for another 10 minutes, and R was n- in the general formula ().
7.8 g of heptyl group aldehyde was gradually added dropwise. After the addition was completed, the mixture was stirred for an additional 10 minutes, and then disappearance of the raw material was confirmed by thin layer chromatography. Isolation and purification of the product from this reaction mixture is described in Reference Example 1.
A sulfone alcohol in which R is an n-heptyl group in the general formula ()
11.0g (80%) was obtained. The MP and various analysis results of this product were completely the same as those of the sulfone alcohol obtained in Reference Example 1. Reference Examples 6 to 8 Instead of 7.8 g of the aldehyde in which R is an n-heptyl group in the general formula () used in Reference Example 5, aldehydes in which R in the general formula () is a cyclohexyl group, an isopropyl group, or a phenyl group, respectively, were used. The same operation as in Reference Example 5 was carried out except that 8.7 g, 5.6 g, and 8.3 g were used, respectively, and 10.8 g (75 %), 8.5g (69%) 8.8
g (63%) was obtained. These mp and various analytical results were in good agreement with those of the sulfone alcohols obtained in Reference Examples 2, 3, and 4, respectively. Reference Example 9 In the general formula () obtained in Reference Example 1, R is n-
Dissolve 11.3 g of sulfonic alcohol, which is a heptyl group, in 200 ml of acetone, cool it in an ice-water bath, and then dropwise add Jones reagent while stirring. After the reaction mixture maintained its red color, disappearance of the starting material was confirmed by thin layer chromatography. Isopropanol was added dropwise until the reaction mixture turned green to decompose excess Jones reagent, and then the solvent was distilled off under reduced pressure. Approximately 100 ml of water was added to the resulting residue to dissolve it well, and the mixture was extracted three times with 50 ml of ether. The organic layers were combined, washed successively with water and brine, and then dried over anhydrous magnesium sulfate. The oil obtained by distilling off the solvent under reduced pressure was diluted with about 20 ml of a mixed solvent of hexane-ethyl acetate (5:1), and then adsorbed onto 20 g of silica gel, which had been inactivated in advance with about 2 ml of water. Ta. After leaving it overnight,
This was placed on the top of an approximately 200 g silica gel column and purified by development using a mixed solvent of hexane and ethyl acetate to obtain 5.9 g (87%) of a colorless liquid. The following analysis results confirmed that this product was a hydroxyketone in the general formula () in which R was an n-heptyl group. IR analysis: ~3450, 3010, 2950, 2930, 2870,
1705, 1210, 1080, 1035 cm ^{-1 1} H-NMR analysis δ ^ppm _CDCl3 : 0.88 (3H, t, J=6
Hz), 1.0-2.1 (9H), 2.44 (2H, t, J=7
Hz), 2.56 (2H, t, J=7Hz), 3.64 (2H, t,
J=6Hz) MS analysis: 158 [M ⁺ ] HighMS: Actual value 158.13068 Calculated value 158.13068 (C ₉ H ₁₈ O ₂ ) Reference example 10 Sulfone alcohol in which R is a heptyl group in the general formula () used in Reference example 9 11.3
6.6 g (91%) of a colorless liquid was obtained by performing the same operation as in Reference Example 9, using 11.8 g of a sulfonic alcohol of the general formula () in which R is a cyclohexyl group, which was synthesized in the same manner as in Reference Example 2, instead of g. Obtained.
The following analysis results confirmed that this product was a hydroxyketone in the general formula () in which R was a cyclohexyl group. IR analysis: 3425, 3005, 2930, 2850, 1700, 1450,
1085, 1030cm ^{-1 1} H-NMR analysis δ ^ppm _CDCl3 1.00-2.12 (13H), 2.36
(1H, m), 2.58 (2H, t, J=6Hz), 3.63
(2H, t, J=6Hz) MS analysis: 170 [M ⁺ ] HighMS: Actual value 170.13290 Calculated value 170.13490 (C ₁₀ H ₁₈ O ₂ ) Reference example 11 In the general formula () used in Reference example 9, R is heptyl Sulfonic alcohols 11.3
The same procedure as in Reference Example 9 was carried out using 10.1 g of a sulfonic alcohol synthesized in the same manner as in Reference Example 3 in which R is an isopropyl group in place of 10.1 g of sulfonic alcohol synthesized in the same manner as in Reference Example 3 to obtain 2.83 g (51%) of a colorless liquid. Obtained. The following analysis results confirmed that this product was a hydroxyketone in the general formula () in which R was an isopropyl group. IR analysis: 3425, 3010, 2970, 2930, 2870, 1700,
1460, 1380, 1360, 1210, 1090, 1040cm ^{-1 1} H-NMR analysis: 1.11 (6H, d, J = 6Hz), 1.4
~2.2 (including 3H, m, OH ), 2.4~2.8 (3H,
m), 3.66 (2H, t, J = 6Hz) MS analysis: 130 [M ⁺ ] HighMS: Actual value 130.09836 Calculated value 130.09736 (C ₇ H ₁₄ O ₂ ) Reference example 12 General formula used in Reference example 9 () Sulfonic alcohol 11.3 in which R is a heptyl group
The same operation as in Reference Example 9 was carried out using 11.6 g of sulfonic alcohol synthesized in the same manner as in Reference Example 4, in which R is a phenyl group, in place of 11.6 g of sulfonic alcohol synthesized in the same manner as in Reference Example 4, to obtain 4.8 g (69%) of a colorless liquid. Obtained. According to the analysis results below, this product has R in the general formula ().
was confirmed to be a hydroxyketone with a phenyl group. IR analysis: 3425, 3010, 1680, 1600, 1445, 1210,
1090, 1000cm ^{-1 1} H-NMR analysis: 2.03 (2H, m), 3.15 (2H, t,
J=7Hz), 3.76 (2H, t, J=6Hz), 7.32~
8.20 (5H, m) MS analysis: 164 [M ⁺ ] HighMS: Actual value 164.08535 Calculated value 164.08375 (C ₁₀ H ₁₂ O ₂ ) Reference example 13 Dissolve 8.49 g of sulfone () in 500 ml of tetrahydrofuran and heat to -78°C. After cooling, 1.1 equivalents of n-butyllithium solution was gradually added dropwise while stirring under a nitrogen atmosphere to generate an anion (). After continuing stirring at -78°C for 10 minutes, in the general formula (), R is an n-heptyl group and R ²
10.1 g of an ester in which is a methyl group was gradually added dropwise. After the addition was completed, stirring was continued for another 10 minutes, and disappearance of the raw material was confirmed by thin layer chromatography. After about 1 ml of water was added to the reaction mixture, the cooling bath was removed and the mixture was stirred for a while at room temperature. The solvent was distilled off under reduced pressure, and about 100 ml of water was added to the resulting residue, which was extracted three times with 100 ml of methylene chloride. The organic layers were combined, washed with brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting concentrate was mixed with about 20 ml of hexane-ethyl acetate (5:1).
After diluting with a mixed solvent, the mixture was adsorbed onto 20 g of silica gel, which had been previously inactivated with about 2 ml of water. After standing overnight, this was placed on the top of a 200 g silica gel column and purified by developing with a mixed solvent of hexane and ethyl acetate to obtain 5.8 g (71% from sulfone) of a colorless liquid. . In this product, in the general formula () obtained in Reference Example 9, R is n-
Various analysis results were in good agreement with hydroxyketone, which is a heptyl group. Reference Example 14 In the general formula () obtained in Reference Example 9, R is n-
10ml of 5.0g of hydroxyketone, which is a heptyl group.
was dissolved in benzene, 0.2 ml of pyridine was added, and after sufficiently cooling in an ice water bath, 5.8 g of thionyl chloride was added dropwise over about 5 minutes with stirring. After the dropwise addition was completed, the bath was removed and stirring was continued for 30 minutes at room temperature. Approximately 10 minutes
Heat to about 80℃, cool, and add about 100ml of the reaction mixture.
Pour into ice water and stir well. After extraction three times with about 20 ml of ether, the organic layers were combined and washed successively with water, sodium bicarbonate solution, and brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the resulting yellow liquid was purified by silica gel column chromatography (using a hexane-ether mixed solvent as a developing solvent) to give 4.5 g (81%). A pale yellow liquid was obtained. From the following analysis results, it was confirmed that this product was a haloketone having the general formula () in which R was an n-heptyl group. IR analysis: 3010, 2950, 2930, 2870, 1705 cm ^{-1 1} H-NMR analysis: δ ^ppm _CDCl3 0.88 (3H, t, J=6
Hz), 1.0~2.1 (8H), 2.32~2.70 (4H, m),
3.59 (2H, t, J=6Hz) [Effects of the invention] Novel sulfone () provided by the present invention
As is clear from the Examples and Reference Examples, hydroxyketone (), which is a synthetic intermediate for useful substances such as fragrances, agricultural chemicals, and pharmaceuticals, can be produced in a good yield on an industrial scale. Useful as a precursor for ketones ().

Claims (1)

[Claims] 1 formula 2,2-dimethyl-1,3-oxathian-3,3-dioxide represented by