CN108484464A - A kind of method of selective oxidation disulfide - Google Patents
A kind of method of selective oxidation disulfide Download PDFInfo
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- CN108484464A CN108484464A CN201810102187.4A CN201810102187A CN108484464A CN 108484464 A CN108484464 A CN 108484464A CN 201810102187 A CN201810102187 A CN 201810102187A CN 108484464 A CN108484464 A CN 108484464A
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Abstract
The present invention relates to a kind of method of selective oxidation disulfide, a kind of new synthetic method of single sulfone compound shown in formula (I) is disclosed：Using disulfide is raw material shown in formula (II), in the presence of tert-butyl hydroperoxide, oxidation reaction occurs in a solvent, it is after reaction, post-treated to obtain single sulfone compound shown in formula (I).Compared with the conventional method, present invention employs green friendly oxidant tert-butyl hydroperoxide, the use of metallic catalyst is avoided, reaction condition is mild, high selectivity, easy to operate, and substrate applicability is wide, and reaction yield is high.
Description
Technical field
The present invention relates to the new methods that a kind of selective oxidation disulfide generates single sulfone compound, belong to organic synthesis neck
Domain.
Background technology
Sulfone compound has extensive biological activity, and the structure, such as the knot of class containing sulfone are all had in many drugs
Anti-inflammatory agent Meloxicam, antimicrobial Sulfamethoxazole, gout suppressant probenecid and the antidiabetic drug glibenclamide of structure are in addition, such is changed
Object is closed to be obtained for extensively in anti-arrhythmia, heart failure resistance, antitumor drug and agrochemical medicine and pesticide field
Application.In recent years, structure optimization is carried out to sulfone compound, influence of the research structure to bioactivity is found with higher
The sulfone compound of bioactivity, it has also become one of the hot spot that pharmaceutical chemistry circle scholars study.
The synthesis of sulfone compound is mainly obtained by the oxidation of thioether, and the selective oxidation of thioether is at sulfoxide or sulfone
Where the key and difficult point of oxidation reaction.Numerous document reports synthesis of such compound, as Zhang et al. uses mesoporous stone
Black carbonitride/isobutylaldehyde system is aoxidized (Green Chem., 2012,14,1904-1908) under illumination condition；Cai etc.
People is aoxidized (Chem.Lett., 2010,39,368-369) using ammonium ceric nitrate/iodine system；Natarajan et al. was used
Potassium acid sulfate/potassium bromide system is aoxidized (Tetrahedron Letters, 2015,56,4131-4134), has obtained list
Sulfone compound also has document report using selenium catalyst (Molecules, 2015,20,10748-10762), bromination copper catalysis
(Tetrahedron Letters, 2010,51,6255-6258), silver nitrate (Synthesis, 2011,2,277-280) are catalyzed
Disulfide, what is obtained is a sulfoxide or disulfoxide compound, does not obtain single sulphones.But these methods have used
Poison is harmful to expensive reagent or severe reaction conditions, or selective not high easily by substrate oxidation at a sulfoxide, disulfoxide
Or two sulfones, substrate applicability be not wide.Therefore, develop that a kind of raw material is easy to get, the method for high-efficient simple is carried out selectively oxidizing sulfur ether and arrived
Sulfone is very necessary.The present invention is highly selective by disulfide selectivity using cheap green oxidant tert-butyl hydroperoxide
It is oxidized to single sulfone compound, no peroxidating by-product generates, easy to operate, product yield high.
Invention content
The purpose of the present invention is to provide a kind of new method of selective oxidation disulfide, the conjunctions of green close friend's simple and effective
At single sulfone compound.To achieve the above object, the present invention adopts the following technical scheme that：
A kind of method of selective oxidation disulfide, the method carry out as follows：
Disulfide shown in formula (II) is dissolved in solvent, tert-butyl hydroperoxide is added as oxidant, in 30-100
1-24h is reacted at a temperature of DEG C, after reaction (TLC detections), reaction solution is post-treated to obtain single sulfone class chemical combination shown in formula (I)
Object；The amount ratio of disulfide shown in the formula (II) and the substance of the tert-butyl hydroperoxide is 1:2~10；
In formula (II) or formula (I), R is Cl-C6 alkyl, alkoxy, benzyl, alkynyl, alkenyl, heterocycle, phenyl or substituted benzene
Base, the substituted-phenyl are that the substituted bases of H on phenyl are monosubstituted or polysubstituted, and the number of the substituent group is 1-3, described
Substituent group respectively stands alone as C1-C4 alkyl or alkoxy, hydroxyl, aldehyde radical, F, Cl or Br.
The synthetic route of the present invention is as follows：
Preferably, in the above method, in formula (II) or formula (I), R be phenyl, p-methylphenyl, p-methoxyphenyl, 2,
4- 3,5-dimethylphenyls, rubigan or p-bromophenyl.
Further, in the above method, the substance of disulfide and the tert-butyl hydroperoxide shown in the formula (II)
Amount than preferably 1:4~6.
Further, in the above method, the volumetric usage of the solvent is with the amount of the substance of disulfide shown in formula (II)
It is calculated as 2~6 mL/mmol；It is preferred that 2mL/mmol.
Further, in the above method, the solvent is 1,2- dichloroethanes, dichloromethane, chloroform, carbon tetrachloride, second
One kind in nitrile, acetone, ethyl acetate, dioxane, tetrahydrofuran, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide
Or it is a variety of；It is preferred that 1,2- dichloroethanes, dichloromethane or chloroform.
Further, in the above method, the reaction temperature of reaction of the present invention is 30~100 DEG C, preferably 60-90 DEG C.
Further, in the above method, the reaction time of reaction of the present invention is 1-24h, preferably 1.5-10h.
Further, in the above method, post-processing step of the present invention is：After reaction, the water (use of the water is added
Amount recommends to be calculated as 5mL/mmol with the amount of the substance of disulfide shown in formula (II)), extract (3 × 5mL/ with dichloromethane
Mmol), merge organic layer and drying, be concentrated under reduced pressure, with petroleum ether：Ethyl acetate is 20:1 mixed liquor is solvent, column layer
Analysis detaches to obtain single sulfone compound shown in formula (I).
Further, in the above method, sulfone compound shown in formula (I) is one of following compounds：
The structure warp of gained compound (I) of the invention1H NMR、13The methods of C NMR, MS, HRMS are characterized and are confirmed.
Beneficial effects of the present invention：It is following several that disulfide is oxidized to single sulfone compound generally use in the prior art
Catalyst system and catalyzing：Selenium catalyst, silver nitrate, copper bromide metallic catalyst are such as used, expensive, selectivity is low, is easy oxidation
At a sulfoxide or disulfoxide, without single sulfone product；Using carbon nitride catalyst, aerobic gas and illumination, condition harshness；Using nitric acid
When cerium ammonium/iodine, potassium hydrogen persulfate/potassium bromide make catalyst, complicated dicyandiamide solution is used；And the technology of the present invention is using nonmetallic
Cheap reagent, mild condition, reagent is simple, and substrate selective can be oxidized to single sulfone under suitable dosage, will not be into one
Step is oxidized to two sulfones, and yield can reach 80% or more substantially.The present invention is easy to operate, and reaction condition is mild, high selectivity, product
High income, substrate applicability is wide, meets the requirement of Green Chemistry.
Specific embodiment
With specific embodiment, the following further describes the technical solution of the present invention below, but protection scope of the present invention
It is without being limited thereto.
Embodiment 1
Diphenyl disulfide (20mmol, 4.36g) is sequentially added in 100mL single port bottles, mass fraction is 70% tertiary butyl
Hydrogen peroxide (100mmol, 12.86g) and 40mL chloroforms react 1.5h at 65 DEG C.(TLC monitorings) after reaction stops adding
Heat after being cooled to room temperature, is added 100mL water, then extract (3 × 100mL) with dichloromethane, merges organic layer and drying, decompression
Concentration, column chromatography (solvent：Petroleum ether：Ethyl acetate=20:1) white object product, yield 89% (4.45g) are obtained.
Fusing point：36-37℃；1H NMR(500MHz,CDCl3)δ7.61-7.54(m,3H),7.51-7.30(m,7H)；13C
NMR(100MHz,CDCl3)δ142.8,136.4,133.4,131.2,129.2,128.6,127.7,127.4；HRMS(ESI)
calcd for C12H10NaO2S2[M+Na]+273.0014；found 273.0014.
Embodiment 2
Two pairs of methylbenzene disulfides (20mmol, 4.92g), 70% t-butyl peroxies are sequentially added in 100mL single port bottles
Change hydrogen (120mmol, 15.43g) and 40mL1,2- dichloroethanes, reacts 3h at 80 DEG C.(TLC monitorings) after reaction stops
Heating after being cooled to room temperature, is added 100mL water, then extract (3 × 100mL) with dichloromethane, merges organic layer and drying, subtract
Pressure concentration, column chromatography (solvent：Petroleum ether：Ethyl acetate=20:1) white object product, yield 90% (5.00g) are obtained.
Fusing point：70-72℃；1H NMR(500MHz,CDCl3) δ 7.49-7.45 (m, 2H), 7.25 (ddd, J=13.0,
10.0,7.9Hz, 4H), 7.16 (d, J=8.0Hz, 2H), 2.44 (s, 3H), 2.39 (s, 3H)；13C NMR(125MHz,
CDCl3)δ 144.6,142.0,140.4,136.5,130.2,129.4,127.6,124.6,21.6,21.5；MS(ESI)
279.3[M+H]+.
Embodiment 3
Di-p-methoxy diphenyl disulfide ether (20mmol, 5.56g), 70% tertiary butyl mistake are sequentially added in 100mL single port bottles
Hydrogen oxide (80mmol, 10.29g) and 40mL dichloromethane react 2h at 60 DEG C.(TLC monitorings) after reaction stops adding
Heat after being cooled to room temperature, is added 100mL water, then extract (3 × 100mL) with dichloromethane, merges organic layer and drying, decompression
Concentration, column chromatography (solvent：Petroleum ether：Ethyl acetate=20:1) white object product, yield 85% (5.27g) are obtained.
Fusing point：84-86℃；1H NMR(500MHz,CDCl3)δ7.53-7.49(m,2H),7.31-7.26(m,2H),
6.91-6.87(m,2H),6.87-6.83(m,2H),3.88(s,3H),3.85(s,3H)；13C NMR(125MHz,CDCl3)δ
163.5,162.2,138.4,134.9,129.9,118.9,114.9,113.8,55.7,55.5；MS(ESI)311.1[M+H]+.
Embodiment 4
Two-(2,4- dimethyl) diphenyl disulfide ethers (20mmol, 5.48g), 70% tertiary fourth are sequentially added in 100mL single port bottles
Base hydrogen peroxide (40mmol, 5.14g) and 40mL1,2- dichloroethanes react 5h at 85 DEG C.(TLC monitorings) after reaction,
Stop heating, after being cooled to room temperature, 100mL water is added, then extract (3 × 100mL) with dichloromethane, merge organic layer and do
It is dry, it is concentrated under reduced pressure, column chromatography (solvent：Petroleum ether：Ethyl acetate=20:1) white object product, yield 80% are obtained
(4.90g)。
Fusing point：59-61℃；1H NMR(500MHz,CDCl3) δ 7.32 (d, J=8.1Hz, 1H), 7.13 (d, J=8.0Hz,
2H),7.03(s,1H),6.96-6.90(m,2H),2.65(s,3H),2.38(s,3H),2.32(s,3H),2.13(s,3H)；13C
NMR(125MHz,CDCl3)δ144.6,143.9,142.3,138.6,138.3,137.6,133.4,131.7,130.2,
127.6, 126.4,123.9,21.4,21.3,20.4,20.3；HRMS(ESI)calcd for C16H18NaO2S2[M+Na]+
329.0640；found 329.0656.
Embodiment 5
Two rubigan disulfides (20mmol, 5.72g), 70% t-butyl peroxy are sequentially added in 100mL single port bottles
Change hydrogen (120mmol, 15.43g) and 40mL chloroforms, reacts 4h at 30 DEG C.(TLC monitorings) after reaction stops heating, cold
But to 100mL water after room temperature, is added, then with dichloromethane (3 × 100mL) is extracted, merges organic layer and drying, is concentrated under reduced pressure,
Column chromatography (solvent：Petroleum ether：Ethyl acetate=20:1) white object product, yield 87% (5.53g) are obtained.
Fusing point：131-134℃；1H NMR(500MHz,CDCl3)δ7.56-7.50(m,2H),7.47-7.42(m,2H),
7.39-7.35(m,2H),7.35-7.30(m,2H)；13C NMR(125MHz,CDCl3)δ141.3,140.6,138.6,137.7,
129.9,129.3,128.9,126.0；MS(ESI)318.8[M+H]+.
Embodiment 6
Two p-bromophenyl disulfides (20mmol, 7.52g), 70% t-butyl peroxy are sequentially added in 100mL single port bottles
Change hydrogen (200mmol, 25.72g) and 40mL chloroforms, reacts 10h at 90 DEG C.(TLC monitorings) after reaction stops heating, cold
But to 100mL water after room temperature, is added, then with dichloromethane (3 × 100mL) is extracted, merges organic layer and drying, is concentrated under reduced pressure,
Column chromatography (solvent：Petroleum ether：Ethyl acetate=20:1) white object product, yield 73% (5.96g) are obtained.
Fusing point：148-152℃；1H NMR(500MHz,CDCl3)δ7.64-7.59(m,2H),7.55-7.51(m,2H),
7.47-7.43(m,2H),7.28-7.23(m,2H)；13C NMR(125MHz,CDCl3)δ141.9,137.8,132.9,132.3,
129.2,129.0,127.0,126.6；MS(ESI)409.2[M+H]+。
Claims (8)
1. a kind of method of selective oxidation disulfide, it is characterised in that the method carries out as follows：
Disulfide shown in formula (II) is dissolved in solvent, tert-butyl hydroperoxide is added as oxidant, in 30-100 DEG C of temperature
Degree is lower to react 1-24h, and after reaction, reaction solution is post-treated to obtain single sulfone compound shown in formula (I)；The formula (II)
Shown in the amount ratio of substance of disulfide and the tert-butyl hydroperoxide be 1:2~10；
In formula (II) or formula (I), R is Cl-C6 alkyl, alkoxy, benzyl, alkynyl, alkenyl, heterocycle, phenyl or substituted-phenyl, institute
It is monosubstituted or polysubstituted for the substituted bases of H on phenyl to state substituted-phenyl, the number of the substituent group is 1-3, the substitution
Base respectively stands alone as C1-C4 alkyl or alkoxy, hydroxyl, aldehyde radical, F, Cl or Br.
2. the method as described in claim 1, it is characterised in that：R is phenyl, p-methylphenyl, p-methoxyphenyl, 2,4- bis-
Aminomethyl phenyl, rubigan or p-bromophenyl.
3. the method as described in claim 1, it is characterised in that：The solvent is 1,2- dichloroethanes, dichloromethane, chlorine
Imitative, carbon tetrachloride, acetonitrile, acetone, ethyl acetate, dioxane, tetrahydrofuran, N,N-dimethylformamide, N, N- dimethyl
It is one or more in acetamide.
4. the method as described in claim 1, it is characterised in that：The volumetric usage of the solvent is with two sulphur shown in formula (II)
The amount of the substance of ether is calculated as 2~6mL/mmol.
5. the method as described in claim 1, it is characterised in that：Disulfide shown in formula (II) and the tert-butyl hydroperoxide
Substance amount ratio be 1:4~6.
6. the method as described in claim 1, it is characterised in that：The reaction temperature of the reaction is 60-90 DEG C.
7. the method as described in claim 1, it is characterised in that：The reaction time of the reaction is 1.5-10h.
8. the method as described in claim 1, it is characterised in that the post-processing is：After reaction, water is added, uses dichloromethane
Alkane extracts, and merges organic layer and drying, is concentrated under reduced pressure, with petroleum ether：Ethyl acetate is 20:1 mixed liquor is solvent, column layer
Analysis detaches to obtain single sulfone compound shown in formula (I).
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111100047A (en) * | 2018-10-29 | 2020-05-05 | 中国石油化工股份有限公司 | Thioether oxidation process |
| CN112047902A (en) * | 2020-09-21 | 2020-12-08 | 上海大学 | Preparation method of asymmetric disulfide compound |
| CN112391644A (en) * | 2020-10-23 | 2021-02-23 | 云南民族大学 | Preparation method of disulfoxide compound |
-
2018
- 2018-02-01 CN CN201810102187.4A patent/CN108484464A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| E.A.ZABURDAEVA等: "Oxidation of organic sulfides and disulfides with a tert-butyl hydroperoxide-aluminum tri-tert-butoxide system", 《RUSSIAN CHEMICAL BULLETIN》 * |
| RAJJAKFUR RAHAMAN等: "A Sulfonylation Reaction: Direct Synthesis of 2-Sulfonylindoles from Sulfonyl Hydrazides and Indoles", 《SYNLETT》 * |
| 童踔: "亚砜(砜)类化合物及(E)-β-碘代烯基砜类化合物的合成研究", 《万方学术期刊数据库》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111100047A (en) * | 2018-10-29 | 2020-05-05 | 中国石油化工股份有限公司 | Thioether oxidation process |
| CN111100047B (en) * | 2018-10-29 | 2021-09-07 | 中国石油化工股份有限公司 | Thioether oxidation process |
| CN112047902A (en) * | 2020-09-21 | 2020-12-08 | 上海大学 | Preparation method of asymmetric disulfide compound |
| CN112391644A (en) * | 2020-10-23 | 2021-02-23 | 云南民族大学 | Preparation method of disulfoxide compound |
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