WO2001062719A1 - Selective oxidation of sulfides by the use of an oxidant system consisting of lithium molibdenate niobate and hydrogen peroxide - Google Patents

Selective oxidation of sulfides by the use of an oxidant system consisting of lithium molibdenate niobate and hydrogen peroxide Download PDF

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WO2001062719A1
WO2001062719A1 PCT/KR2001/000252 KR0100252W WO0162719A1 WO 2001062719 A1 WO2001062719 A1 WO 2001062719A1 KR 0100252 W KR0100252 W KR 0100252W WO 0162719 A1 WO0162719 A1 WO 0162719A1
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sulfone
sulfoxide
mmol
sulfide
hydrogen peroxide
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PCT/KR2001/000252
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French (fr)
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Sangho Koo
Kwanghyun Ahn
Songho Byeon
Jaedeuk Yang
Minkoo Ji
Soojin Choi
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Sangho Koo
Kwanghyun Ahn
Songho Byeon
Jaedeuk Yang
Minkoo Ji
Soojin Choi
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Priority to AU2001236161A priority Critical patent/AU2001236161A1/en
Publication of WO2001062719A1 publication Critical patent/WO2001062719A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B45/00—Formation or introduction of functional groups containing sulfur
    • C07B45/04—Formation or introduction of functional groups containing sulfur of sulfonyl or sulfinyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C315/00—Preparation of sulfones; Preparation of sulfoxides
    • C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides

Definitions

  • the present invention relates to a process for preparing a sulfoxide or a sulfone, which is very important intermediate for synthesis of pharmaceuticals or natural compounds, via oxidation of a sulfide.
  • R and R * independently represent an alkyl. alkenyl. vinyl, allyl, propargyl or aryl group.
  • a sulfide compound is primarily oxidized to a sulfoxide compound, which is then further oxidized to a sulfone compound by oxidant.
  • oxidant oxidant
  • oxidants usable for oxidizing a sulfide include NaI0 , oxone, and the like.
  • oxidation of phenyl prenyl sulfide was tried in the presence of methyl alcohol solvent (Table 1 , Ex.3 - Ex.6) by the inventors.
  • sulfoxide compound [A] was mainly obtained regardless of the amount of the oxidant.
  • the selectivity was remarkable when using NaI0 4 as oxidant.
  • oxidation to sulfoxide [A] was easy, but oxidation to sulfone [B] was difficult, as was the reaction using hydrogen peroxide/acetic acid oxidant system.
  • MCPBA meta-chloroperbenzoic acid among the oxidants
  • epoxy sulfone compound [C] was obtained in 62% yield as well as sulfone compound [B] in 22% yield.
  • selective oxidation could be performed by controlling the amount of MCPBA, an oxidant having strong electrophilicity.
  • MCPBA an oxidant having strong electrophilicity.
  • excess amount of MCPBA by the use of excess amount of MCPBA, oxidation of the double bond as well as oxidation of sulfide was progressed to give epoxy sulfone compound [C].
  • MCPBA is employed in an excess amount, since the accurate amount cannot be evaluated as it is commercially merchandised in 60 - 80% purity. Especially, oxidation of the double bond should occur in case of performing the oxidation in a large scale. What is critical is that the MCPBA is expensive, and involves the problem of treating meta-chlorobenzoic acid as by-product, so that it can be hardly employed industrially.
  • sulfone [B] was very selectively obtained without providing oxidation of the double bond nor production of sulfoxide [A]
  • 64 - 74% of sulfoxide was obtained, but with about 10 - 20% of sulfone [B] as by-product.
  • the oxidant system consisting of metal oxide as catalyst and hydrogen peroxide as oxidant is suitable for oxidation of allylic sulfide having double bond of increased electron density by alkyl substituent(s), to sulfone.
  • the inventors evaluated the ability of selective oxidation of allylic sulfide having double bond of increased electron density due to extended conjugation to sulfoxide and sulfone. respectively, by using metal oxide as catalyst and controlling the amount of hydrogen peroxide as oxidant. Oxidation was attempted by using phenyl 3,7,1 1-trimethy 1-2,4,6, 10-dodecatetraenyl sulfide as the allylic sulfide, Nb 2 0 5 , Mo0 3 , V 2 0 5 , MeRe0 3 , Na 2 W0 4 , or the like as metal oxide catalyst, and 1 equivalent or 2 equivalents of hydrogen peroxide. The results are shown in Table 3.
  • the inventors paid intensive efforts to develop a process for selective oxidation of allylic sulfide comprising double bond(s) with high electron density due to many alkyl substituents or conjugation to the corresponding sulfoxide or sulfone, and eventually developed lithium molibdenate niobate(LiNbMo0 6 )-H 2 0 2 oxidant system.
  • the present invention provides a process of selective oxidation for preparing a sulfoxide or a sulfone compound from the corresponding sulfide by the use of an oxidant system consisting of LiNbMo0 6 as a composite metal oxide and H 2 0 2 as a quantitative oxidant, in the presence of alcoholic solvent and under the condition of controlling the amount of the quantitative oxidant.
  • a sulfoxide or a sulfone compound is synthesized in high yield under the condition of adding 1 equivalent or 2 or more equivalents (preferably, 3 equivalents) of hydrogen peroxide as quantitative oxidant in the presence of LiNbMo0 6 catalyst and alcohol solvent (preferably, methanol) at room temperature.
  • the quantitative oxidant is preferably added at 0°C.
  • R and R' are defined as above, and R" represents a lower alkyl group.
  • the inventors could obtain the corresponding sulfoxide or sulfone from a sulfide in high yield by using LiNbMo0 6 as composite metal oxide catalyst and hydrogen peroxide as quantitative oxidant under the condition of adding 1 equivalent or 2 equivalents of hydrogen peroxide, respectively, at 0°C to room temperature in the presence of alcohol solvent (preferably, methanol), to complete the invention.
  • alcohol solvent preferably, methanol
  • the object of the present invention is to provide a process for selective oxidation of a sulfide compound, especially, an allylic sulfide comprising double bond(s) with high electron density due to a multiple of alkyl substituents or conjugation, to the corresponding sulfoxide or sulfone.
  • the oxidant system according to the present invention LiNbMo0 6 - H 2 0 2 is very efficient on oxidation of an allylic sulfide having double bond of high electron density due to many alkyl substituents or conjugation, differently from MCPBA with high electrophilicity or hydrogen peroxide-acetic acid system.
  • the process provides selective synthesis of the desired sulfoxide or sulfone by controlling the amount of hydrogen peroxide as quantitative oxidant. without oxidizing the double bond to epoxy group.
  • an oxidant having low electrophilicity requires long reaction time owing to low reactivity in case of oxidation to a sulfide, and provides low selectivity of oxidation to sulfoxide or sulfone.
  • the composite metal catalyst LiNbMo0 6 employed in the present invention can be prepared with relative ease (Kar. T.; Choudhary, R. N. P.. Materials Lett. 1997,
  • the oxidant system LiNbMo0 6 - H 2 0 2 , is a very good oxidant system with excellent reactivity and selectivity to sulfoxide or sulfone in spite of its weak electrophilicity.
  • the oxidant system can provide the corresponding sulfoxide or sulfone compound from a sulfide within a few hours at ambient temperature with high selectivity and good yield.
  • the catalyst LiNbMo0 6 is added to the sulfide solution in an amount of 0.01 to 0.1 equivalent, preferably about 0.05 equivalent, and then 1 equivalent (in case of sulfoxide) or 2 or more equivalents (in case of sulfone) of about 30%) aqueous hydrogen peroxide solution is slowly added thereto.
  • reaction temperature is preferably maintained at 10°C or lower, more preferably at 0°C.
  • the oxidation is completed within about 1 hour in case of a sulfoxide, or about 4 hours in case of a sulfone.
  • the product can be purified by simply concentrating the obtained reaction mixture and subjected to a column chromatography. If in a large scale, the product is preferably worked-up by adding chloroform to the reaction mixture, washing with water, drying and concentrating, and then purified.
  • Example 1 Preparation of phenyl prenyl sulfoxide and sulfone
  • phenyl prenyl sulfide (0.71 g, 4.0 mmol) was dissolved in methanol (20 ml), and the solution was well stirred at 0°C.
  • methanol 20 ml
  • LiNbMo0 6 58 mg, 0.2 mmol
  • 30% aqueous hydrogen peroxide solution (1.20 g, 12.0 mmol
  • phenyl prenyl sulfide (0.60 g, 3.3 mmol) was dissolved in methanol (20 ml), and the solution was well stirred at room temperature.
  • methanol 20 ml
  • LiNbMoO ⁇ 49 mg, 0.2 mmol
  • 30% aqueous hydrogen peroxide solution 1.20 g, 12.0 mmol
  • chloroform 80 ml was added, and the mixture was well washed with distilled water (20 ml x 3), dried over anhydrous sodium sulfate, and filtered.
  • phenyl 3,7,1 l-trimethyl-2.4, 6.10-dodecatetraenyl sulfone was prepared as follows: In a mixture of benzene (30 ml) and methanol (70 ml), phenyl 3,7,1 l-trimethyl-2,4,6, 10-dodecatetraenyl sulfide having trans-/cis- ratio [on the double bond of C-2] of about 2.5: 1 (16.1 g, 51.5 mmol) was dissolved.
  • geranyl phenyl sulfone was prepared as follows: To a solution of geranyl phenyl sulfide (2.80 g, 1 1.4 mmol) dissolved in methanol (45 ml), was added LiNbMoO 6 (0.17 g, 0.60 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (3.86 g, 34.1 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1. to give the objective sulfone (2.68 g, 9.6 mmol. yield: 85%).
  • the NMR data of the obtained geranyl phenyl sulfone are shown below:
  • allyl phenyl sulfone was prepared as follows: To a solution of allyl phenyl sulfide (0.50 g, 3.4 mmol) dissolved in methanol (16 ml), was added LiNbMoO ⁇ (49 mg, 0.20 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (1.00 g, 10.1 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1. to give the objective sulfone (0.54 g, 3.0 mmol, yield: 85%>).
  • the NMR data of the obtained allyl phenyl sulfone are shown below:
  • crotyl phenyl sulfone was prepared as follows: To a solution of crotyl phenyl sulfide (1.64 g, 10.0 mmol) dissolved in methanol (50 ml), was added LiNbMoO 6 (0.15 g, 0.50 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (3.40 g, 30.0 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone ( 1.91 g, 9.7 mmol, yield: 97%o).
  • the NMR data of the obtained crotyl phenyl sulfone are shown below:
  • phenyl propargyl sulfone was prepared as follows: To a solution of phenyl propargyl sulfide ( 1.58 g, 10.7 mmol) dissolved in methanol (50 ml), was added LiNbMo0 6 (0.16 g, 0.50 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (3.60 g, 32.0 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone (1.62 g, 9.0 mmol, yield: 84%>).
  • Example 7 Preparation of 4-hydroxyprenyl phenyl sulfoxide and sulfone To a solution of 4-hydroxyprenyl phenyl sulfide (97 mg, 0.5 mmol) dissolved in methanol (2.5 ml), was added LiNbMoO ⁇ (7.3 mg, 0.05 mmol) as a catalyst, and then 34%) aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto. After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1. to give pure 4-hydroxyprenyl phenyl sulfoxide (79 mg, 0.38 mmol, yield: 75%).
  • 4-hydroxyprenyl phenyl sulfone was prepared as follows: To a solution of 4-hydroxyprenyl phenyl sulfide (0.60 g, 3.2 mmol) dissolved in methanol (15 ml), was added LiNbMo0 6 (46 mg, 0.20 mmol) as a catalyst, and then 30%) aqueous hydrogen peroxide solution (0.96 g, 9.5 mmol) was slowly added thereto.
  • benzyl phenyl sulfone was prepared as follows: To a solution of benzyl phenyl sulfide (2.00 g, 10.0 mmol) dissolved in methanol (50 ml), was added LiNbMo0 6 (0.15 mg, 0.50 mmol) as a catalyst, and then 30%) aqueous hydrogen peroxide solution (3.40 g, 30.0 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1 , to give the objective sulfone (2.27 g, 9.8 mmol, yield: 98%).
  • the NMR data of the obtained benzyl phenyl sulfone are shown below:
  • Example 9 Preparation of diprenyl sulfoxide and sulfone To a solution of diprenyl sulfide (85 mg, 0.50 mmol) dissolved in methanol
  • LiNbMo0 6 (7.3 mg, 0.05 mmol) as a catalyst, and then 34% aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto.
  • diprenyl sulfone was prepared as follows: To a solution of diprenyl sulfide (0.60 g. 3.5 mmol) dissolved in methanol (18 ml), was added LiNbMo0 6 (51 mg, 0.20 mmol) as a catalyst, and then 30%> aqueous hydrogen peroxide solution (1.00 g, 10.1 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone (0.43 g, 2.1 mmol. yield: 71%o).
  • the NMR data of the obtained diprenyl sulfone are shown below:
  • digeranyl sulfone was prepared as follows: To a solution of digeranyl sulfide (3.57 g, 1 1.7 mmol) dissolved in methanol (40 ml), was added LiNbMo0 6 (0.17 g, 0.60 mmol) as a catalyst, and then 30%> aqueous hydrogen peroxide solution (3.96 g, 35.0 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone (2.84 g, 8.4 mmol, yield: 72%).
  • the NMR data of the obtained digeranyl sulfone are shown below:
  • the present invention provides a process for selectively preparing a sulfoxide or a sulfone compound from the corresponding sulfide by the use of LiNbMo0 6 -H 2 0 2 oxidant system having both reactivity and selectivity, under the condition of controlling the quantitative amount of the oxidant.
  • the process according to the present invention is economically advantageous as the process employs cheap hydrogen peroxide as the quantitative oxidant, and easily carried out as it employs LiNbMo0 6 as a composite metal oxide catalyst which is ready to handle with good stability at room temperature.
  • the process is carried out in high yield under mild condition, and the reaction product can be easily worked-up.
  • the process according to the present invention is very efficient on the oxidation of an allylic sulfide comprising double bond(s) with high electron density to a sulfone which was very difficult to be obtained by means of conventional processes.

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Abstract

The present invention relates to a process for selective oxidation of a sulfide by the use of lithium molibdenate niobate (LiNbMoO6) - hydrogen peroxide oxidant system to the corresponding sulfoxide or sulfone compound within a few hours under the condition of controlling the amount of hydrogen peroxide in the presence of alcohol solvent. The process for oxidizing a sulfide according to the present invention has economic advantage in view of the application for industrial use as well as in a laboratory scale because the process is carried out under mild condition, comprising of simple procedure, and the reactants are easy to handle. In particular, allylic sulfides having double bond(s) of high electron density by alkyl substitution or extended conjugation, which are apt to be attacked by electrophilic oxidants, can be subjected to selective oxidation to sulfones or sulfoxides without oxidation of the double bond(s), according to the present invention.

Description

SELECTIVE OXIDATION OF SULFIDES BY THE USE OF AN OXIDANT SYSTEM CONSISTING OF LITHIUM MOLIBDENATE NIOBATE AND
HYDROGEN PEROXIDE
Technical Field
The present invention relates to a process for preparing a sulfoxide or a sulfone, which is very important intermediate for synthesis of pharmaceuticals or natural compounds, via oxidation of a sulfide.
R R'
Figure imgf000002_0001
In the formulas, R and R* independently represent an alkyl. alkenyl. vinyl, allyl, propargyl or aryl group.
Background Art A sulfide compound is primarily oxidized to a sulfoxide compound, which is then further oxidized to a sulfone compound by oxidant. In general, it has been known that synthesis of sulfoxide via selective oxidation by the use of only one equivalent of oxidant has difficulties in controlling the reaction condition, even though a sulfone compound can be synthesized with comparative ease by using excess amount of oxidant.
For oxidation of a sulfide to a sulfoxide or a sulfone, a process of using hydrogen peroxide in the presence of acetic acid solvent has been well known (Oae, S.; Dawi. T.; Furukawa. N. Tetrahedron Lett. 1984, 25, 69; Paquette, L. A.; Carr, R. V. C. Org. Synth. 1985, 64, 157). By means of the reaction conditions, selective oxidation of phenyl prenyl sulfide to the corresponding sulfone and sulfoxide has been tried by the present inventors, as described in the reaction formula below and Table 1. Under the condition of using excess amount of hydrogen peroxide (3 equivalents) in the presence of acetic acid solvent at room temperature for 24 hours, only sulfoxide [A] was obtained in 90% yield without producing sulfone [B] at all (Ex.l of Table 1 ). Under the same condition but the reaction was carried out at 70°C, sulfoxide [A], sulfone [B] and epoxy sulfone [C] were obtained in 5%, 5% and 12% yield, respectively (Ex.2 of Table 1). Throughout the reaction, the yield was low because it is thought that allylic sulfide is unstable under acidic condition with heating. According to the process, selective synthesis of the sulfoxide (which was thought to be difficult) was rather easy, but the selective synthesis of sulfone compound [B] was difficult.
Other oxidants usable for oxidizing a sulfide include NaI0 , oxone, and the like. By the use of these oxidants, oxidation of phenyl prenyl sulfide was tried in the presence of methyl alcohol solvent (Table 1 , Ex.3 - Ex.6) by the inventors. In these cases, sulfoxide compound [A] was mainly obtained regardless of the amount of the oxidant. In particular, the selectivity was remarkable when using NaI04 as oxidant. According to the processes, oxidation to sulfoxide [A] was easy, but oxidation to sulfone [B] was difficult, as was the reaction using hydrogen peroxide/acetic acid oxidant system.
In order to achieve efficient oxidation of a sulfide to the corresponding sulfone, oxidants with strong electrophilicity are used. It is reported that meta-chloroperbenzoic acid among the oxidants (hereinafter, abbreviated to as "MCPBA") can selectively oxidize a sulfide compound to the corresponding sulfoxide when used in an equivalent amount at low temperature (usually, -78 °C to 0 °C) in the presence of dichloromethane solvent, while selectively oxidize a sulfide to the corresponding sulfone when used in an amount of two equivalents at room temperature (Nicolaou, K. C; Magolda, R. L.; Sipio, W. J.; Barnette, W. E.; Lysenko, Z.; Joullie. M. M., J. Am. Chem. Soc. 1980. 102, 3784). According to the processes described above, the inventors also attempted selective oxidation of phenyl prenyl sulfide (Table 1, Ex.7 - Ex.9). Sulfoxide compound [A] was obtained in 75% yield when one equivalent of MCPBA was slowly added to the sulfide at 0 °C, and the reaction mixture was stirred for 4 hour at the same temperature and then another 4 hours at room temperature, while sulfone compound [B] was obtained in an excellent yield of 91% when using 2 equivalents of MCPBA under the same condition. In the meanwhile, under the condition of using 3 equivalents of MCPBA with stirring at room temperature for 4 hours, epoxy sulfone compound [C] was obtained in 62% yield as well as sulfone compound [B] in 22% yield. In other word, selective oxidation could be performed by controlling the amount of MCPBA, an oxidant having strong electrophilicity. However, in case of oxidizing prenyl sulfide containing a double bond with high degree of alkyl substitution, by the use of excess amount of MCPBA, oxidation of the double bond as well as oxidation of sulfide was progressed to give epoxy sulfone compound [C]. Practically, MCPBA is employed in an excess amount, since the accurate amount cannot be evaluated as it is commercially merchandised in 60 - 80% purity. Especially, oxidation of the double bond should occur in case of performing the oxidation in a large scale. What is critical is that the MCPBA is expensive, and involves the problem of treating meta-chlorobenzoic acid as by-product, so that it can be hardly employed industrially.
Oxidant
Figure imgf000004_0001
Condition
Figure imgf000004_0002
[Table 1 ]
Figure imgf000004_0003
Thus, in order to achieve selective oxidation of allylic sulfide to the corresponding sulfoxide or sulfone without involving oxidation of double bond(s), which is practically available in the industrial field, development of an oxidant with appropriate reactivity and electrophilic property to some extent has been required. As the oxidant of this type, an oxidant system using quantitative amount of hydrogen peroxide with metal oxide catalyst has been reported (Schultz, H. S.; Freyermuth, H. B.; Buc, S. R., J. Org. Chem. 1963, 28, 1 140). Selective oxidation of phenyl prenyl sulfide was attempted by using either 1 equivalent or 3 equivalents of hydrogen peroxide with Mo03, V205, MeRe03, Na2W04, or the like as a metal oxide catalyst (Table 2). In case of using Mo03 as a catalyst, sulfoxide [A] was mainly obtained regardless of the amount of hydrogen peroxide, and the selectivity was not very good (Ex.1 and Ex.2 of Table 2). In case of performing the oxidation by using MeRe03 as a catalyst with 1 equivalent of hydrogen peroxide, the sulfoxide compound [A] was obtained as the main product (Ex.5), while with 3 equivalents of hydrogen peroxide, epoxy sulfone [C] was obtained in 41% yield since oxidation of the double bond also occurred as was in the case of using MCPBA (Ex.6 of Table 2). Differently from the above two cases, when V205 or Na2W04 was used, sulfoxide and sulfone could be obtained in a relatively good selectivity and yield, respectively, by means of controlling the amount of hydrogen peroxide (Ex.3, Ex.4. Ex.7 and Ex.8 of Table 2). In particular, in case of using 3 equivalents of hydrogen peroxide, sulfone [B] was very selectively obtained without providing oxidation of the double bond nor production of sulfoxide [A], However, in the attempt of synthesizing sulfoxide [A] by the use of 1 equivalent of hydrogen peroxide, 64 - 74% of sulfoxide was obtained, but with about 10 - 20% of sulfone [B] as by-product. Thus, the oxidant system consisting of metal oxide as catalyst and hydrogen peroxide as oxidant is suitable for oxidation of allylic sulfide having double bond of increased electron density by alkyl substituent(s), to sulfone.
Figure imgf000006_0001
[Table 2]
Figure imgf000006_0004
Then, the inventors evaluated the ability of selective oxidation of allylic sulfide having double bond of increased electron density due to extended conjugation to sulfoxide and sulfone. respectively, by using metal oxide as catalyst and controlling the amount of hydrogen peroxide as oxidant. Oxidation was attempted by using phenyl 3,7,1 1-trimethy 1-2,4,6, 10-dodecatetraenyl sulfide as the allylic sulfide, Nb205, Mo03, V205, MeRe03, Na2W04, or the like as metal oxide catalyst, and 1 equivalent or 2 equivalents of hydrogen peroxide. The results are shown in Table 3.
Oxidant
Figure imgf000006_0003
Condition
Figure imgf000006_0002
[Table 3]
Figure imgf000007_0001
Differently from the allylic sulfide with double bond of increased electron density due to alkyl substituent(s), selective oxidation of allylic sulfide comprising conjugated double bond(s) to the corresponding sulfoxide or sulfone was very difficult, and no good result could be obtained in terms of selectivity and yield by the use of the metal oxide catalyst as above (Ex.1 to Ex.10 of Table 3). On the contrary, when oxidation of phenyl 3,7, 1 l-trimethyl-2,4,6, 10-dodecatetraenyl sulfide was attempted by using MCPBA (which resulted in selective oxidation of phenyl prenyl sulfide to the corresponding sulfoxide and sulfone), selective oxidation to sulfoxide could be achieved by using 1 equivalent of the oxidant, but selective oxidation to sulfone [E] by using 2 equivalents of the oxidant was not easily performed (Ex. l 1 and Ex.12 of Table 3). It is thought that the product yield is lowered in the process owing to the generation of various by-products such as epoxy sulfone. Thus, it is practically needed to develop more efficient metal oxide catalyst to achieve selective oxidation of allylic sulfide having double bond of increased electron density due to conjugation, not only the sulfϊdes having double bond of increased electron density by alkyl substituent(s), to the corresponding sulfoxide or sulfone.
Disclosure of the Invention
The inventors paid intensive efforts to develop a process for selective oxidation of allylic sulfide comprising double bond(s) with high electron density due to many alkyl substituents or conjugation to the corresponding sulfoxide or sulfone, and eventually developed lithium molibdenate niobate(LiNbMo06)-H202 oxidant system. The present invention provides a process of selective oxidation for preparing a sulfoxide or a sulfone compound from the corresponding sulfide by the use of an oxidant system consisting of LiNbMo06 as a composite metal oxide and H202 as a quantitative oxidant, in the presence of alcoholic solvent and under the condition of controlling the amount of the quantitative oxidant. According to the present invention, a sulfoxide or a sulfone compound is synthesized in high yield under the condition of adding 1 equivalent or 2 or more equivalents (preferably, 3 equivalents) of hydrogen peroxide as quantitative oxidant in the presence of LiNbMo06 catalyst and alcohol solvent (preferably, methanol) at room temperature. In order to enhance the selectivity of oxidation to sulfoxide. the quantitative oxidant is preferably added at 0°C.
R
Figure imgf000008_0001
In the formulas, R and R' are defined as above, and R" represents a lower alkyl group.
As described above, when MCPBA or hydrogen peroxide-AcOH system is employed as an electrophilic oxidant to prepare a sulfone from an allylic sulfide having double bond(s) of high electron density, epoxy sulfone is produced by oxidation of the double bond(s). Thus, a development of oxidant having both reactivity and selectivity at ambient temperature with weak electrophilicity was required. As a result of intensive studies, the inventors could obtain the corresponding sulfoxide or sulfone from a sulfide in high yield by using LiNbMo06 as composite metal oxide catalyst and hydrogen peroxide as quantitative oxidant under the condition of adding 1 equivalent or 2 equivalents of hydrogen peroxide, respectively, at 0°C to room temperature in the presence of alcohol solvent (preferably, methanol), to complete the invention.
The object of the present invention is to provide a process for selective oxidation of a sulfide compound, especially, an allylic sulfide comprising double bond(s) with high electron density due to a multiple of alkyl substituents or conjugation, to the corresponding sulfoxide or sulfone. The oxidant system according to the present invention, LiNbMo06 - H202 is very efficient on oxidation of an allylic sulfide having double bond of high electron density due to many alkyl substituents or conjugation, differently from MCPBA with high electrophilicity or hydrogen peroxide-acetic acid system. The process provides selective synthesis of the desired sulfoxide or sulfone by controlling the amount of hydrogen peroxide as quantitative oxidant. without oxidizing the double bond to epoxy group. In general, an oxidant having low electrophilicity requires long reaction time owing to low reactivity in case of oxidation to a sulfide, and provides low selectivity of oxidation to sulfoxide or sulfone.
The composite metal catalyst LiNbMo06 employed in the present invention can be prepared with relative ease (Kar. T.; Choudhary, R. N. P.. Materials Lett. 1997,
32, 109), and is easy to handle with good stability at room temperature. The oxidant system, LiNbMo06 - H202, is a very good oxidant system with excellent reactivity and selectivity to sulfoxide or sulfone in spite of its weak electrophilicity. Thus, the oxidant system can provide the corresponding sulfoxide or sulfone compound from a sulfide within a few hours at ambient temperature with high selectivity and good yield. According to preferred embodiment of the present invention, it is necessary to obtain an intimate solution when dissolving the sulfide compound in methanol; thus, in case of a sulfide with low solubility, a certain amount of benzene is added to obtain complete dissolution. The catalyst LiNbMo06 is added to the sulfide solution in an amount of 0.01 to 0.1 equivalent, preferably about 0.05 equivalent, and then 1 equivalent (in case of sulfoxide) or 2 or more equivalents (in case of sulfone) of about 30%) aqueous hydrogen peroxide solution is slowly added thereto.
In order to improve the selectivity on the oxidation to sulfoxide. the reaction temperature is preferably maintained at 10°C or lower, more preferably at 0°C.
The oxidation is completed within about 1 hour in case of a sulfoxide, or about 4 hours in case of a sulfone. If the reaction is carried out in a small scale, the product can be purified by simply concentrating the obtained reaction mixture and subjected to a column chromatography. If in a large scale, the product is preferably worked-up by adding chloroform to the reaction mixture, washing with water, drying and concentrating, and then purified.
Examples
Processes for preparing sulfoxides or sulfones via selective oxidation of sulfides in accordance with the present invention are now described in more detail by referring to the examples below, but it should be noticed that the present invention is not restricted to the examples by any means.
Example 1 : Preparation of phenyl prenyl sulfoxide and sulfone In a 100 ml round-bottomed flask, phenyl prenyl sulfide (0.71 g, 4.0 mmol) was dissolved in methanol (20 ml), and the solution was well stirred at 0°C. To the solution, was added LiNbMo06 (58 mg, 0.2 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (1.20 g, 12.0 mmol) was slowly added thereto. After stirring the resultant mixture at 0°C for 4 hours, the solvent was removed by evaporation under reduced pressure. Thus obtained crude product was purified by silica gel column chromatography to give pure phenyl prenyl sulfoxide (0.60 g, 3.1 mmol, yield: 77%). The sulfone (0.12 g, yield: 14%) was also obtained. The NMR data of the obtained phenyl prenyl sulfoxide are shown below:
1H-NMR δ 1.32 (3H, s), 1.64 (3H, s), 3.52 (1H, dd of A part of ABq, Jd = 8.0, 12.5, JAB = 12.5 Hz), 3.59 ( 1H, dd of B part of ABq, Jd = 7.5, 12.5, JAB = 12.5 Hz),
4.99 (1H, t, J = 7.9 Hz), 7.39 - 7.53 (5H, m).
In a 100 ml round-bottomed flask, phenyl prenyl sulfide (0.60 g, 3.3 mmol) was dissolved in methanol (20 ml), and the solution was well stirred at room temperature. To the solution, was added LiNbMoOό (49 mg, 0.2 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution ( 1.20 g, 12.0 mmol) was slowly added thereto. After stirring the resultant mixture at room temperature for 4 hours, chloroform (80 ml) was added, and the mixture was well washed with distilled water (20 ml x 3), dried over anhydrous sodium sulfate, and filtered. After removing the solvent under reduced pressure, the crude product was purified by silica gel column chromatography to obtain pure phenyl prenyl sulfone (0.56 g, 2.7 mmol, yield: 82%). The NMR data of the obtained phenyl prenyl sulfone are shown below:
Η-NMR δ 1.31 (3H, s), 1.72 (3H, s), 3.79 (2H, d, J = 7.9 Hz), 5.19 ( lH, t,
J = 7.9 Hz), 7.52 - 7.88 (5H, m).
Example 2: Preparation of phenyl 3.7.1 l-trimethyl-2,4, 6, 10-dodecatetraenyl sulfoxide and sulfone
In a 25 ml round-bottomed flask, phenyl
3,7,1 l-trimethyl-2,4,6, 10-dodecatetraenyl sulfide having trans-/cis- ratio [on the double bond of C-2] of about 2.5: 1 ( 156 mg, 0.5 mmol) was dissolved in a mixture of methanol (2.0 ml) and benzene (0.5 ml), and the solution was well stirred at 0°C. To the solution, was added LiNbMo06 (7 mg, 0.025 mmol) as a catalyst, and then 34% aqueous hydrogen peroxide solution (50 μL. 0.5 mmol) was slowly added thereto.
After stirring the resultant mixture at room temperature for 2.5 hours, the solvent was removed by evaporation under reduced pressure. Thus obtained crude product was purified by silica gel column chromatography to give phenyl 3,7,1 l-trimethyl-2,4,6, 10-dodecatetraenyl sulfoxide having trans-/cis- ratio [on the double bond of C-2] of about 2.5: 1 (131 mg, 0.4 mmol, yield: 80%). The sulfone (7 mg, yield: 4%>) was also obtained. The NMR data of the obtained sulfoxide are shown below: Η-NMR δ 1.59 (3H, s), 1.63 (3H, s), 1.70 (3H, s), 1.81 (3H, s), 2.12 (4H. br s), 3.71 ( IH, d of A of ABq, Jd = 8.6, JAB = 12.8 Hz), 3.78 (IH. d of B of ABq, Jd = 8.2, JAB = 12.8 Hz), 5.13 (IH, br s), 5.29 (IH, t, J = 8.4 Hz), 5.90 (IH. d, J = 10.9 Hz), 6.14 (IH, d, J = 15.2 Hz), 6.44 (IH. dd, J = 15.2, 10.9 Hz), 7.47 - 7.55 (3H, m), 7.57 - 7.65 (2H, m).
In the meanwhile, phenyl 3,7,1 l-trimethyl-2.4, 6.10-dodecatetraenyl sulfone was prepared as follows: In a mixture of benzene (30 ml) and methanol (70 ml), phenyl 3,7,1 l-trimethyl-2,4,6, 10-dodecatetraenyl sulfide having trans-/cis- ratio [on the double bond of C-2] of about 2.5: 1 (16.1 g, 51.5 mmol) was dissolved. To the solution, LiNbMoO6 (301 mg, 1.03 mmol) and 35% aqueous hydrogen peroxide solution ( 12.5 g, 0.129 mol) were sequentially added at 0°C, and the resultant reaction mixture was stirred at 25 °C for 6 hours. Then, the mixture was worked up according to the same procedure of Example 1 , to give 3,7, 1 l-trimethyl-2.4, 6, 10-dodecatetraenyl sulfone (13.7 g, 39.8 mmol, yield: 77%). The sulfone had trans-/cis- ratio [on the double bond of C-2] of about 2.5: 1 , but the trans- and cis-sulfone could be separated by column chromatography. The NMR data of each sulfone are shown below:
Η-NMR (trans-) δ 1.60 (3H, s), 1.68 (3H, s), 1.71 (3H, s), 1.78 (3H, s), 2.09 (4H, br s), 3.67 (2H, d, J = 8.0 Hz), 5.10 (IH, br s), 5.57 (IH, t, J = 8.0 Hz). 5.89 ( IH, d, J = 1 1.0 Hz), 6.16 (IH, d, J = 15.2 Hz), 6.40 (IH, dd. J = 15.2, 1 1.0 Hz), 7.12 - 7.44 (5H, m)
Η-NMR (cis-) δ 1.60 (3H, s). 1.68 (3H, s), 1.79 (3H. s). 1.88 (3H, s), 2.10 (4H, br s), 3.73 (2H, d, J = 7.9 Hz), 5.10 (IH. br s), 5.44 (IH. t, J = 7.9 Hz). 5.93 (IH, d, J = 1 1.5 Hz), 6.16 (IH, d, J = 15.2 Hz), 6.47 (IH, dd. J = 15.2. 1 1.0 Hz), 7.12 - 7.44 (5H, m) Example 3: Preparation of geranyl phenyl sulfoxide and sulfone
To a solution of geranyl phenyl sulfide (123 mg, 0.50 mmol) dissolved in methanol (2.5 ml), was added LiNbMo06 (7.3 mg, 0.05 mmol) as a catalyst, and then 34%o aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto. After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1 , to give pure geranyl phenyl sulfoxide ( 102 mg, 0.39 mmol, yield: 78%). Geranyl phenyl sulfone ( 19 mg, 0.07 mmol, yield: 14%) was also obtained. The NMR data of the obtained geranyl phenyl sulfoxide are shown below: Η-NMR δ 1.42 (3H, s). 1.59 (3H, s), 1.69 (3H, s), 2.02 (4H, br s), 3.54
( IH. d of A part of ABq, Jd = 8.1 , JAB = 12.7 Hz), 3.63 ( IH, d of B part of ABq, Jd = 7.8, 12.5, JAB = 12.7 Hz). 5.05 (2H, t, J = 7.7 Hz), 7.47 - 7.54 (3H, m), 7.57 = 7.64 (2H, m)
In the meanwhile, geranyl phenyl sulfone was prepared as follows: To a solution of geranyl phenyl sulfide (2.80 g, 1 1.4 mmol) dissolved in methanol (45 ml), was added LiNbMoO6 (0.17 g, 0.60 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (3.86 g, 34.1 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1. to give the objective sulfone (2.68 g, 9.6 mmol. yield: 85%). The NMR data of the obtained geranyl phenyl sulfone are shown below:
Η-NMR δ 1.31 (3H, s), 1.59 (3H, s), 1.69 (3H, s). 2.00 (4H. br s), 3.81 (2H, d, J = 8.1 Hz). 5.03 (IH, br s), 5.19 ( IH, t, J = 8.1 Hz). 7.51 - 7.89 (5H, m).
Example 4: Preparation of allyl phenyl sulfoxide and sulfone
To a solution of allyl phenyl sulfide (75 mg, 0.50 mmol) dissolved in methanol (2.5 ml), was added LiNbMo06 (7.3 mg, 0.05 mmol) as a catalyst, and then 34% aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto. After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1, to give pure allyl phenyl sulfoxide (76 mg. 0.46 mmol. yield: 91%). Allyl phenyl sulfone (4 mg, 0.02 mmol, yield: 4%) was also obtained. The NMR data of the obtained allyl phenyl sulfoxide are shown below:
Η-NMR δ 3.49 (IH, d of A part of ABq, Jd = 7.5, JAB = 12.8 Hz), 3.57 ( IH, d of B part of ABq, Jd = 7.5, JAB = 12.8 Hz), 5.18 (IH, dd, J = 1.0, 16.0 Hz), 5.32 ( IH, dd, J = 0.6, 9.8 Hz), 5.63 (IH. ddt, Jd = 9.8, 16.0, Jt = 7.5 Hz), 7.49 - 7.61 (5H, m).
In the meanwhile, allyl phenyl sulfone was prepared as follows: To a solution of allyl phenyl sulfide (0.50 g, 3.4 mmol) dissolved in methanol (16 ml), was added LiNbMoOό (49 mg, 0.20 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (1.00 g, 10.1 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1. to give the objective sulfone (0.54 g, 3.0 mmol, yield: 85%>). The NMR data of the obtained allyl phenyl sulfone are shown below:
Η-NMR δ 3.82 (2H, d, J = 6.0 Hz), 5.16 ( lH, ddd, J = 1.1 , 2.2, 16.4 Hz), 5.33 (IH, ddd, J = 0.8, 1.6, 7.9 Hz), 5.78 (IH. ddt, Jd - 7.9, 16.4, Jt = 6.0 Hz), 7.54 -
7.89 (5H, m)
Example 5: Preparation of allyl phenyl sulfoxide and sulfone
To a solution of crotyl phenyl sulfide (82 mg, 0.50 mmol) dissolved in methanol (2.5 ml), was added LiNbMo06 (7.3 mg, 0.05 mmol) as a catalyst, and then
34%o aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto. After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1 , to give pure crotyl phenyl sulfoxide (79 mg, 0.44 mmol, yield: 88%). Crotyl phenyl sulfone (10 mg, 0.05 mmol, yield: 10%) was also obtained. The NMR data of the obtained crotyl phenyl sulfoxide are shown below:
Η-NMR δ 1.66 (3H. dd. J = 0.6, 6.5 Hz), 3.41 (IH, d of A part of ABq, Jd = 7.5, JAB = 12.7 Hz), 3.47 (IH, dd of B part of ABq, Jd = 7.5, JAB = 12.7 Hz), 5.28 (IH, ddt, Jd = 1.6, 15.2, Jt= 7.3 Hz). 5.58 (IH, dq, Jq = 6.5, Jd = 15.2 Hz), 7.46 - 7.60 (5H, m). In the meanwhile, crotyl phenyl sulfone was prepared as follows: To a solution of crotyl phenyl sulfide (1.64 g, 10.0 mmol) dissolved in methanol (50 ml), was added LiNbMoO6 (0.15 g, 0.50 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (3.40 g, 30.0 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone ( 1.91 g, 9.7 mmol, yield: 97%o). The NMR data of the obtained crotyl phenyl sulfone are shown below:
1H-NMR δ 1.67 (3H, d, J = 6.2 Hz), 3.74 (2H, d, J = 7.1 Hz), 5.42 ( IH, ddt, Jd = 1.3, 15.3, J, = 7.2 Hz), 5.56 ( IH, dq, Jq = 6.3, Jd = 15.3 Hz), 7.32 - 7.90 (5H,m).
Example 6: Preparation of phenyl propargyl sulfoxide and sulfone
To a solution of phenyl propargyl sulfide (74 mg, 0.50 mmol) dissolved in methanol (2.5 ml), was added LiNbMo06 (7.3 mg, 0.05 mmol) as a catalyst, and then 34%o aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto. After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1 , to give pure phenyl propargyl sulfoxide (76 mg, 0.46 mmol, yield: 93%). Phenyl propargyl sulfone (5 mg, 0.03 mmol, yield: 6%) was also obtained. The NMR data of the obtained phenyl propargyl sulfoxide are shown below: Η-NMR δ 2.35 (IH, t, J = 2.7 Hz), 3.62 ( I H. d of A part of ABq, Jd = 2.8.
JAB = 15.8 Hz), 3.68 ( IH, d of B part of ABq, Jd = 2.8, JAB = 15.8 Hz), 7.52 - 7.58 (3H, m), 7.67 - 7.73 (5H, m).
In the meanwhile, phenyl propargyl sulfone was prepared as follows: To a solution of phenyl propargyl sulfide ( 1.58 g, 10.7 mmol) dissolved in methanol (50 ml), was added LiNbMo06 (0.16 g, 0.50 mmol) as a catalyst, and then 30% aqueous hydrogen peroxide solution (3.60 g, 32.0 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone (1.62 g, 9.0 mmol, yield: 84%>). The NMR data of the obtained phenyl propargyl sulfone are shown below: Η-NMR δ 2.40 (lH, t, J = 2.6 Hz), 3.99 (2H, d, J = 2.6 Hz), 7.58 - 7.66 (3H, m), 7.70 - 7.76 (IH, m), 7.79 - 8.03 (2H, m).
Example 7: Preparation of 4-hydroxyprenyl phenyl sulfoxide and sulfone To a solution of 4-hydroxyprenyl phenyl sulfide (97 mg, 0.5 mmol) dissolved in methanol (2.5 ml), was added LiNbMoOό (7.3 mg, 0.05 mmol) as a catalyst, and then 34%) aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto. After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1. to give pure 4-hydroxyprenyl phenyl sulfoxide (79 mg, 0.38 mmol, yield: 75%). At the same time, 4-hydroxyprenyl phenyl sulfone ( 14 mg, 0.06 mmol. yield: 12%) was also obtained. The NMR data of the obtained 4-hydroxyprenyl phenyl sulfoxide are shown below:
Η-NMR δ 1.39 (3H, s), 3.45 (IH, br s ), 3.58 ( IH, d of A part of ABq, Jd = 8.1, JAB = 12.8 Hz), 3.61 ( IH, d of B part of ABq, Jd = 8.1, JAB = 12.8 Hz), 3.95 (2H, s), 5.40 (IH, t, J = 8.1 Hz), 7.46 - 7.60 (5H, m).
In the meanwhile, 4-hydroxyprenyl phenyl sulfone was prepared as follows: To a solution of 4-hydroxyprenyl phenyl sulfide (0.60 g, 3.2 mmol) dissolved in methanol (15 ml), was added LiNbMo06 (46 mg, 0.20 mmol) as a catalyst, and then 30%) aqueous hydrogen peroxide solution (0.96 g, 9.5 mmol) was slowly added thereto.
After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone (0.67 g, 3.0 mmol, yield: 95%>). The NMR data of the obtained 4-hydroxyprenyl phenyl sulfone are shown below: Η-NMR δ 1.34 (3H. s), 2.98 (lH. br s), 3.87 (2H, d, J = 8.1 Hz), 3.97 (2H, s), 5.53 (IH, dt, Jd = 1.4, Jt = 8.1 Hz), 7.52 - 7.89 (5H, m).
Example 8: Preparation of benzyl phenyl sulfoxide and sulfone
To a solution of benzyl phenyl sulfide (100 mg, 0.50 mmol) dissolved in methanol (2.5 ml), was added LiNbMo06 (7.3 mg, 0.05 mmol) as a catalyst, and then 34%o aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto. After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1, to give pure benzyl phenyl sulfoxide (102 mg, 0.47 mmol, yield: 94%>). At the same time, benzyl phenyl sulfone (3 mg, 0.01 mmol, yield: 3%) was also obtained. The NMR data of the obtained benzyl phenyl sulfoxide are shown below:
Η-NMR δ 3.99 (IH, A part of ABq, JAB = 12.6 Hz), 4.08 (IH, B part of ABq, JAB = 12.6 Hz), 6.96 - 7.01 (2H, m), 7.20 - 7.31 (3H, m), 7.33 - 7.49 (5H, m).
In the meanwhile, benzyl phenyl sulfone was prepared as follows: To a solution of benzyl phenyl sulfide (2.00 g, 10.0 mmol) dissolved in methanol (50 ml), was added LiNbMo06 (0.15 mg, 0.50 mmol) as a catalyst, and then 30%) aqueous hydrogen peroxide solution (3.40 g, 30.0 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1 , to give the objective sulfone (2.27 g, 9.8 mmol, yield: 98%). The NMR data of the obtained benzyl phenyl sulfone are shown below:
Η-NMR δ 4.67 (2H, s), 7.13 -7.28 (5H, m), 7.51 - 7.72 (5H, m).
Example 9: Preparation of diprenyl sulfoxide and sulfone To a solution of diprenyl sulfide (85 mg, 0.50 mmol) dissolved in methanol
(2.5 ml), was added LiNbMo06 (7.3 mg, 0.05 mmol) as a catalyst, and then 34% aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto.
After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1. to give pure diprenyl sulfoxide (50 mg, 0.27 mmol, yield: 54%). At the same time, diprenyl sulfone (108 mg, 0.53 mmol, yield: 6%>) was also obtained. The NMR data of the obtained diprenyl sulfone are shown below: Η-NMR δ 1.74 (6H, s), 1.85 (6H, s), 3.66 (4H, d, J = 7.7 Hz), 5.30 (2H, t,
J = 7.7 Hz).
In the meanwhile, diprenyl sulfone was prepared as follows: To a solution of diprenyl sulfide (0.60 g. 3.5 mmol) dissolved in methanol (18 ml), was added LiNbMo06 (51 mg, 0.20 mmol) as a catalyst, and then 30%> aqueous hydrogen peroxide solution (1.00 g, 10.1 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone (0.43 g, 2.1 mmol. yield: 71%o). The NMR data of the obtained diprenyl sulfone are shown below:
Η-NMR δ 1.67 (6H, s), 1.78 (6H. s), 3.60 (4H, d, J = 7.7 Hz), 5.23 (2H, t, J = 7.7 Hz)
Example 10: Preparation of digeranyl sulfoxide and sulfone To a solution of digeranyl sulfide ( 153 mg, 0.50 mmol) dissolved in methanol
(2.5 ml), was added LiNbMo06 (7.3 mg, 0.05 mmol) as a catalyst, and then 34% aqueous hydrogen peroxide solution (50 mg, 0.50 mmol) was slowly added thereto. After stirring at 0°C for 1 hour, the reaction mixture was worked up according to the same procedure of Example 1, to give pure digeranyl sulfoxide (77.4 mg, 0.24 mmol, yield: 48%). At the same time, digeranyl sulfone (12 mg, 0.04 mmol, yield: 7%>) was also obtained. The NMR data of the obtained digeranyl sulfone are shown below:
Η-NMR δ 1.61 (6H, s), 1.69 (6H, s), 1.73 (6H, s), 2.14 (8H, br s), 3.67 (4H, d, J = 7.7 Hz), 5.08 (2H, br s), 5.30 (2H. t, J = 7.7 Hz).
In the meanwhile, digeranyl sulfone was prepared as follows: To a solution of digeranyl sulfide (3.57 g, 1 1.7 mmol) dissolved in methanol (40 ml), was added LiNbMo06 (0.17 g, 0.60 mmol) as a catalyst, and then 30%> aqueous hydrogen peroxide solution (3.96 g, 35.0 mmol) was slowly added thereto. After stirring at room temperature for 4 hours, the reaction mixture was worked up according to the same procedure of Example 1, to give the objective sulfone (2.84 g, 8.4 mmol, yield: 72%). The NMR data of the obtained digeranyl sulfone are shown below:
Η-NMR δ 1.61 (6H, s), 1.68 (6H, s), 1.72 (6H, s), 2.13 (8H, br s), 3.66 (4H, d, J = 7.7 Hz), 5.07 (2H, br s), 5.29 (2H. t, J = 7.7 Hz).
Chemical structures of the reactant and the product, and the yield of each reaction described in Examples 1 - 10 are listed in Table 4. Table 4
Ex. Allylic sulfide Yield of sulfoxιde(sulfone) Yield of sulfone
Figure imgf000019_0001
,SPh 91 %(4%) 88%
^SPh 88%(10%) 97%
SPh
93%(6%) 84%
HO.
^SPh 75%(12%) 95%
0"SPh 94%(3%) 98%
Figure imgf000019_0002
Figure imgf000019_0003
As can be seen from the Examples, the present invention provides a process for selectively preparing a sulfoxide or a sulfone compound from the corresponding sulfide by the use of LiNbMo06 -H202 oxidant system having both reactivity and selectivity, under the condition of controlling the quantitative amount of the oxidant. The process according to the present invention is economically advantageous as the process employs cheap hydrogen peroxide as the quantitative oxidant, and easily carried out as it employs LiNbMo06 as a composite metal oxide catalyst which is ready to handle with good stability at room temperature. The process is carried out in high yield under mild condition, and the reaction product can be easily worked-up. In addition, the process according to the present invention is very efficient on the oxidation of an allylic sulfide comprising double bond(s) with high electron density to a sulfone which was very difficult to be obtained by means of conventional processes.

Claims

1. A process of selective oxidation for preparing a sulfoxide or a sulfone compound from the corresponding sulfide by the use of an oxidant system consisting of LiNbMo06 as a composite metal oxide catalyst and H202 as a quantitative oxidant, in the presence of alcoholic solvent and under the condition of controlling the amount of the quantitative oxidant.
Figure imgf000021_0001
In the formulas, R and R' independently represent an alkyl, alkenyl, vinyl, allyl, propargyl or aryl group, and R" represents lower alkyl group.
2. A process of selective oxidation for preparing a sulfoxide or a sulfone compound from the corresponding sulfide according to claim 1 , wherein R or R' of the compound represents allyl group comprising a double bond with high electron density due to alkyl substituent(s) or conjugation.
3. A process according to claim 1 , wherein the selectivity of oxidation is enhanced by using 0.01 to 0.1 equivalent of the catalyst and maintaining the reaction temperature under 10°C during the oxidation to sulfoxide.
4. A process of selective oxidation for preparing a sulfoxide compound from the corresponding sulfide according to claim 1, which comprises the steps of dissolving 1 equivalent of a sulfide compound in alcohol solvent, adding 0.01 to 0.1 equivalent of LiNbMo06 catalyst thereto, and further adding 1 equivalent of aqueous H202 solution at a temperature under 10°C.
5. A process of selective oxidation for preparing a sulfone compound from the corresponding sulfide according to claim 1. which comprises the steps of dissolving 1 equivalent of a sulfide compound in alcohol solvent, adding 0.01 to 0.1 equivalent of LiNbMo06 catalyst thereto, and further adding 2 equivalents or more of aqueous H202 solution at room temperature.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102086167A (en) * 2010-12-09 2011-06-08 济南大学 Method for preparing ethylsulfonyl acetonitrile
RU2668810C1 (en) * 2017-08-07 2018-10-08 Федеральное Государственное Бюджетное Учреждение Науки Институт Химии Коми Научного Центра Уральского Отделения Российской Академии Наук Method for obtaining petroleum sulfoxides
EP3421442A1 (en) 2017-06-28 2019-01-02 Construction Research & Technology GmbH Dispersant for inorganic particles

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4025565A (en) * 1972-02-22 1977-05-24 Asahi Glass Co., Ltd. Process for preparing unsaturated aldehyde having three to four carbon atoms
EP0124845A1 (en) * 1983-05-10 1984-11-14 I.M.F. Industria Macchine Faenza S.P.A. Device for positioning an machining unit relatively to a workpiece, in particular for transfer lines
WO1998013329A1 (en) * 1996-09-24 1998-04-02 E.I. Du Pont De Nemours And Company Molybdenum based oxidation catalysts

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4025565A (en) * 1972-02-22 1977-05-24 Asahi Glass Co., Ltd. Process for preparing unsaturated aldehyde having three to four carbon atoms
EP0124845A1 (en) * 1983-05-10 1984-11-14 I.M.F. Industria Macchine Faenza S.P.A. Device for positioning an machining unit relatively to a workpiece, in particular for transfer lines
WO1998013329A1 (en) * 1996-09-24 1998-04-02 E.I. Du Pont De Nemours And Company Molybdenum based oxidation catalysts

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
A.V. RAMASWAMY AND S. SILVASANKER: "Selective oxidation reactions over titanium and vanadium metallosilicate molecular sieves", CATALYSIS LETTERS, vol. 22, no. 3, 1993, pages 239 - 249 *
CAROLE DUBOC-TOIA ET AL.: "Enantioselective sufoxidation as a prove for a metal-based mechanism in H2O2-dependent oxidation catalyzed by a Diiron complex", INORGANIC CHEMISTRY, vol. 38, no. 6, 1999, pages 1261 - 1268 *
TAKAHIRO IWAHAMA ET AL.: "Selective oxidation of sulfides to sulfoxides with molecular oxygen catalyzed by N-hydroxyphthalimide(NHPI) in the presence of alcohols", TETRAHEDRON LETTERS, vol. 39, no. 49, 1998, pages 9059 - 9062, XP004141002, DOI: doi:10.1016/S0040-4039(98)02054-1 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102086167A (en) * 2010-12-09 2011-06-08 济南大学 Method for preparing ethylsulfonyl acetonitrile
CN102086167B (en) * 2010-12-09 2013-05-08 济南大学 Method for preparing ethylsulfonyl acetonitrile
EP3421442A1 (en) 2017-06-28 2019-01-02 Construction Research & Technology GmbH Dispersant for inorganic particles
RU2668810C1 (en) * 2017-08-07 2018-10-08 Федеральное Государственное Бюджетное Учреждение Науки Институт Химии Коми Научного Центра Уральского Отделения Российской Академии Наук Method for obtaining petroleum sulfoxides

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