CN105218418A - A kind of preparation method of thioether - Google Patents
A kind of preparation method of thioether Download PDFInfo
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- CN105218418A CN105218418A CN201510640231.3A CN201510640231A CN105218418A CN 105218418 A CN105218418 A CN 105218418A CN 201510640231 A CN201510640231 A CN 201510640231A CN 105218418 A CN105218418 A CN 105218418A
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Abstract
A preparation method for thioether is prepared by the reaction formula of following formula (1) or formula (2):
wherein, above-mentioned A
1-R
1-X
1, A
2-R
2-X
2for halides, do not need transition-metal catalyst in this reaction, avoid heavy metal contamination, used sulphur source (sulfide and elemental sulfur) is cheap and easy to get, efficiently simple to operate, and reaction conditions is gentle, cost is low, high safety, is applicable to suitability for industrialized production.
Description
Technical field
The invention belongs to technical field of medical chemistry, be specifically related to a kind of preparation method of thioether.
Background technology
Sulfide based structural unit is extensively present in and manyly has in the natural product of physiologically active and the medicine of synthetic.All there is sulfide based structural unit in the husky medicine such as star, foodstuff additive diallyl thioether of antipsychotics Quetiapine, antimicrobial drug thioether, thus sulfide based structural unit has important using value.
Traditional thioether preparation method is as follows:
Traditional thioether synthesis technique generally needs to add the transition-metal catalysts such as palladium, rhodium, copper or nickel.Such as following several preparation scheme: 1. with three (benzylidene-acetone) two palladium be catalyzer, three (methylbenzene) ethane for part, sodium sulphite is sulphur source (Org.Lett.2011,13,4100 ?4103); 2. be catalyzer with cuprous iodide, elemental sulfur is sulphur source (Organometallics, 2013,32,5514 ?5522); 3. be catalyzer with cuprous iodide, potassium thiocyanate is sulphur source (Chin.J.Chem.2012,30,651 ?655); 4. be catalyzer with neutralized verdigris, potassium ethyl xanthonate is sulphur source (Org.Lett.2011,13,1008 ?1011); 5. be catalyzer with cuprous iodide, thiocarbamide is sulphur source (Tetrahedron.Lett.2015,56,2426 ?2429).The first scheme needs palladium catalyst and Phosphine ligands, wherein catalyzer and part expensive, and palladium catalyst can produce heavy metal waste slag, and Phosphine ligands should not be preserved, therefore is not suitable for suitability for industrialized production.Rear four kinds of schemes adopt copper to make catalyzer, and catalyzer price is relatively inexpensive, avoids the use of Phosphine ligands simultaneously, reduces synthesis technique cost.But in these four kinds of schemes, all can produce heavy metal waste slag, aftertreatment cost is high, and in medicine synthesising process, there is the problems such as heavy-metal residual again.
Summary of the invention
The object of the invention is the weak point overcoming traditional technology, provide a kind of thioether preparation method through improvement, the method does not need transition-metal catalyst, efficiently simple to operate, and agents useful for same is cheap and easy to get, and cost is low, is applicable to suitability for industrialized production.
For reaching above-mentioned purpose, the technical solution adopted in the present invention is: a kind of preparation method of thioether, is to be prepared by the reaction formula of following formula (1) or formula (2):
Wherein, above-mentioned A
1-R
1-X
1, A
2-R
2-X
2for halides, its substituting group has following characteristics: A
1=A
2or A
1≠ A
2; R
1=R
2or R
1≠ R
2; X
1=X
2or X
1≠ X
2.Particularly, this halides A
1-R
1-X
1and halides A
2-R
2-X
2structure be one in following two kinds of situations:
Situation one: as halides A
1-R
1-X
1in R
1for C
1~ C
40fat group, X
1for halogen or trifluoromethanesulfonic acid ester group; A
1during for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, phenyl or benzyl, halides A
2-R
2-X
2structural formula is as follows:
In this structural formula, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group or sulfonate group, X
2for halogen or trifluoromethanesulfonic acid ester group; A ring is had at least to exist in a ring or b ring: when b ring does not exist, Z, M, Q also do not exist; When a, b ring exists and Z, Q, M are all C, A
2be positioned at X
2ortho position or contraposition; When a ring presence or absence, b ring exists and Z, M are C, Q when being N, X
2be positioned at ortho position or the contraposition of Q on b ring; When a ring presence or absence, b ring exist and Z be C, Q, M is when being N, X
2be positioned at optional position on b ring; When a ring presence or absence, b ring exists and Z, Q are N, M when being C, X
2be positioned at optional position on b ring.
Further, above-mentioned X
1during for halogen, be fluorine, chlorine, bromine or iodine; X
2during for halogen, be fluorine, chlorine, bromine or iodine.
Situation two: as halides A
1-R
1-X
1, A
2-R
2-X
2in R
1, R
2during for aryl, halides A
1-R
1-X
1general formula for shown in formula I, halides A
2-R
2-X
2general formula for shown in formula II:
When above-mentioned formula I, II is monocyclic aromatic compounds, this halides A
1-R
1-X
1structure be reduced to general formula III, halides A
2-R
2-X
2structure be reduced to general formulae IV:
In above-mentioned general formula III, IV:
When Z, Q, M are all C, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group or sulfonate group, and A
1be positioned at X
1ortho position or contraposition, A
2be positioned at X
2ortho position or contraposition;
When Z be N, Q, M be C time, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, on pyridine ring 2 or 4, position; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
When Z, Q be N, M are C, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, position is two or three-digit on aromatic nucleus; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
When Z be C, Q, M be N time, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, position is optional position on aromatic nucleus; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl.
When above-mentioned formula I, II is bicyclic aromatic compounds, this halogenide A
1-R
1-X
1structure for shown in general formula V, this halogenide A
2-R
2-X
2structure for shown in general formula VI:
In above-mentioned general formula V, VI:
When Z, Q, M are all C, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group or sulfonate group, and A
1, A
2lay respectively at X
1or X
2ortho position or contraposition;
When Z be N, Q, M be C time, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, be positioned at 2 or 4 of quinoline ring; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
When Z, Q be N, M are C, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, be positioned at the two or three-digit of quinoxaline ring; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
When Z be C, Q, M be N time, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, position is at 2 or 4 of benzo pyrimidine ring; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl.
Further, above-mentioned X
1during for halogen, be fluorine, chlorine, bromine or iodine, X
2during for halogen, be fluorine, chlorine, bromine or iodine.
Solvent in above-mentioned reaction formula (1), reaction formula (2) is selected from the one in toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, N, N-dicarboximide, dimethyl sulfoxide (DMSO), methylene dichloride, acetonitrile, ether, methyl alcohol or ethanol.
Sulfide in above-mentioned reaction formula (1) is selected from M
2s, MSCN or MSCSOR, wherein, M is selected from lithium, sodium, potassium or caesium, and R is selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-or the tertiary butyl.
Elemental sulfur in above-mentioned reaction formula (2) is selected from S
2, S
4, S
6, S
8or the one in amorphous sulfur.
In above-mentioned reaction formula (2), the general formula of alkali is MOR or MY, and wherein, M is selected from lithium, sodium, potassium or caesium; R is selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl or carbonyl; Y is selected from carbonate, phosphate radical, acetate moiety, propionate, butanic acid root, methacrylate, positive pentanoate, isovalerate or PIVALIC ACID CRUDE (25) root.
If no special instructions, S is herein sulphur atom, and C is carbon atom, and N is nitrogen-atoms, and O is Sauerstoffatom.
The preparation process of the inventive method is specific as follows:
1:1:1 gets A in molar ratio
1-R
1-X
1, A
2-R
2-X
2, sulphur source (sulfide or elemental sulfur), 1mmolA pressed by solvent
1-R
1-X
1the ratio of getting 4ml solvent takes, and alkali presses 1mmolA
1-R
1-X
1the ratio of getting 2mmol solvent takes, and reacts by aforesaid reaction formula (1) or reaction formula (2).Particularly, under nitrogen atmosphere protection, by A
1-R
1-X
1, elemental sulfur, alkali and solvent join in reactor, or by A
1-R
1-X
1, sulfide and solvent join in reactor, stirring reaction in 20-180 DEG C of oil bath.Work as A
1-R
1-X
1after reacting completely, reaction system is cooled to room temperature, then by A
2-R
2-X
2join in reactor, in 20-180 DEG C of oil bath, continue stirring reaction.After question response terminates, reaction system is cooled to room temperature, adds water, aqueous phase is extracted with ethyl acetate 3 times, and merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains target product.Work as A
1-R
1-X
1with A
2-R
2-X
2time identical, can join in reactor, stirring reaction in 20-180 DEG C of oil bath simultaneously.
Compared with prior art, tool of the present invention has the following advantages:
1, do not need transition-metal catalyst in reaction, not only avoid heavy metal contamination, and reduce the cost of synthesis technique.
2, used in the reaction sulphur source such as sodium sulphite, simple substance, potassium thiocyanate is cheap and easy to get, and atom utilization is high.
3, used in reaction alkali is some alkali cheap and easy to get.
4, efficiently simple to operate, reaction conditions is gentle, and reagent used is cheap and easy to get, and cost is low, high safety, is applicable to suitability for industrialized production.
Embodiment
Now further illustrate the present invention by following examples, but and non-limiting scope of the present invention.
The preparation of embodiment 1 two-(4-chloro phenyl) thioether
Under nitrogen atmosphere protection; by chloro-for 1-4-oil of mirbane (157mg, 1mmol), sodium sulphite (39mg, 0.5mmol), N; N-dicarboximide (2ml) joins in dry reaction tubes, is suspended in 120 DEG C of oil baths and reacts 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, and merge organic phase, evaporated under reduced pressure solvent, column chromatography obtains yellow solid i.e. two-(4-nitrophenyl) thioethers (132mg, yield is 98%).
The preparation of embodiment 2 (2-nitrophenyl) (4-acetylphenyl) thioether
Under nitrogen atmosphere protection, by 4-bromoacetophenone (99mg, 0.5mmol), thiocarbamide (38mg, 0.5mmol), 1,4-dioxane (2ml) joins in dry reaction tubes, at 80 DEG C of oil bath stirring reaction 12h.After reaction system is cooled to room temperature, 2-bromo nitrobenzene (101mg, 0.5mmol) is added in reaction tubes, be suspended in 140 DEG C of oil baths and react 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times; merge organic phase; evaporated under reduced pressure solvent, column chromatography for separation obtains colorless solid i.e. (2-nitrophenyl) (4-acetylphenyl) thioether (126mg, yield is 92%).
The preparation of embodiment 3 (4-aldehyde radical phenyl) (4-trifluoromethyl) thioether
Under nitrogen atmosphere protection; by 4-chlorobenzotrifluoride (90mg; 0.5mmol), sulphur powder (16mg; 0.5mmol), sodium carbonate (212mg; 2mmol), dimethyl sulfoxide (DMSO) (2ml) joins in dry reaction tubes, at 80 DEG C of oil bath stirring reaction 6h.After reaction system is cooled to room temperature, 4-bromobenzaldehyde (92mg, 0.5mmol) is added in reaction tubes, be suspended in 100 DEG C of oil baths and react 12h.After reaction system is cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains colorless solid i.e. (4-aldehyde radical phenyl) (4-trifluoromethyl) thioether (127mg, yield is 90%).
The preparation of embodiment 4 two-(2 '-pyridyl) thioether
Under nitrogen atmosphere protection, 2-iodine pyridine (103mg, 1mmol), potassium thiocyanate (49mg, 0.5mmol), toluene (2mml) are joined in dry reaction tubes, is suspended in 140 DEG C of oil baths and reacts 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains yellow oily liquid i.e. two-(2 '-pyridyl) thioethers (88mg, yield is 83%).
The preparation of embodiment 5 (4-cyano-phenyl) (2 '-pyrimidyl) thioether
Under nitrogen atmosphere protection; by 2-trifluoromethanesulfonic acid yl pyrimidines (112mg; 0.5mmol), potassium ethyl xanthonate (80mg, 0.5mmol), tetrahydrofuran (THF) (2ml) join in dry reaction tubes, at 80 DEG C of oil bath stirring reaction 12h.After reaction system is cooled to room temperature, 4-chlorobenzene cyanogen (69mg, 0.5mmol) is added in reaction tubes, be suspended in 140 DEG C of oil baths and react 12h.After reaction system is cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains yellow oily liquid i.e. (4-cyano-phenyl) (2 '-pyrimidyl) thioether (101mg, yield is 95%).
The preparation of embodiment 6 two-(5 '-pyrimidyl) thioether
Under nitrogen atmosphere protection; by 5-bromo pyrimi piperidine (159mg; 1mmol), sulphur powder (16mg; 0.5mmol), salt of wormwood (138mg; 1mmol), N; N-dicarboximide (2ml) joins in dry reaction tubes, is suspended in 140 DEG C of oil baths and reacts 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains yellow oily liquid i.e. two-(5 '-pyrimidyl) thioethers (87mg, yield is 95%).
The preparation of embodiment 7 (the bromo-2 '-pyridyl of 5-) (2 '-quinolyl) thioether
Under nitrogen atmosphere protection, 2-chloroquinoline (82mg, 0.5mmol), thiocarbamide (38mg, 0.5mmol), ether (2ml) are joined in dry reaction tubes, at 60 DEG C of oil bath stirring reaction 2h.After reaction system is cooled to room temperature, fluoro-for 2-5-bromopyridine (88mg, 0.5mmol) is added in reaction tubes, be suspended in 100 DEG C of oil baths and react 12h.After reaction system is cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains yellow solid i.e. (the bromo-2 '-pyridyl of 5-) (2 '-quinolyl) thioether (149mg, yield is 94%).
The preparation of embodiment 8 two-(2 '-quinoxalinyl) thioether
Under nitrogen atmosphere protection; by 2-trifluoromethanesulfonic acid base quinoxaline (274mg; 1mmol), potassium thiocyanate (49mg, 0.5mmol), acetonitrile (2ml) join in dry reaction tubes, is suspended in 140 DEG C of oil baths and reacts 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains yellow solid i.e. two-(2 '-quinoxalinyl) thioethers (140mg, yield is 97%).
The preparation of embodiment 9 (4-nitrophenyl) (2 '-pyrazinyl) thioether
Under nitrogen atmosphere protection; by 4-nitro-chlorobenzene (101mg, 0.5mmol), potassium ethyl xanthonate (80mg, 0.5mmol), N; N-dicarboximide (2ml) joins in dry reaction tubes, at 40 DEG C of oil bath stirring reaction 2h.After reaction system is cooled to room temperature, 2-bromo-pyrazine (80mg, 0.5mmol) is added in reaction tubes, be suspended in 80 DEG C of oil baths and react 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains yellow solid i.e. (4-nitrophenyl) (2 '-pyrazinyl) thioether (111mg, yield is 95%).
The preparation of embodiment 10 di-n-butyl thioether
Under nitrogen atmosphere protection; by n-butyl bromide (136mg, 1mmol), potassium ethyl xanthonate (80mg, 0.5mmol), N; N-dicarboximide (2ml) joins in dry reaction tubes, is suspended in 120 DEG C of oil baths and reacts 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, and merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains colourless oil liquid and di-n-butyl thioether.(71mg, yield is 95%).
The preparation of embodiment 11 2-propyl carbinol base thioether
Under nitrogen atmosphere protection; by bromo-for 4-n-butyl alcohol (153mg, 1mmol), sodium sulphite (39mg, 0.5mmol), N; N-dicarboximide (2ml) joins in dry reaction tubes, is suspended in 140 DEG C of oil baths and reacts 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, and merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains yellow oily liquid i.e. two-propyl carbinol base thioether (81mg, yield is 95%).
The preparation of embodiment 12 (2 '-quinolyl) n-butyl sulfide
Under nitrogen atmosphere protection, 2-bromine quinoxaline (105mg, 0.5mmol), potassium ethyl xanthonate (80mg, 0.5mmol), N, N-dicarboximide (2ml) are joined in dry reaction tubes.React 4h in 20 DEG C of oil baths after, then trifluoromethanesulfonic acid base butane (101mg, 0.5mmol) is added in reaction tubes, be suspended in 120 DEG C of oil baths and react 12h.After reaction system being cooled, add 15ml water, aqueous phase ethyl acetate 30ml extracts 3 times, merge organic phase, evaporated under reduced pressure solvent, column chromatography for separation obtains yellow solid i.e. (2 '-quinolyl) n-butyl sulfide (205mg, yield is 94%).
Claims (8)
1. a preparation method for thioether, is characterized in that, is to be prepared by the reaction formula of following formula (1) or formula (2):
Wherein, A
1-R
1-X
1, A
2-R
2-X
2for halides, the one in following two kinds of situations:
Situation one: as halides A
1-R
1-X
1in R
1for C
1~ C
40fat group, X
1for halogen or trifluoromethanesulfonic acid ester group; A
1during for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, phenyl or benzyl, halides A
2-R
2-X
2structural formula is as follows:
In this structural formula, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group or sulfonate group, X
2for halogen or trifluoromethanesulfonic acid ester group; Have at least a ring to exist in a ring or b ring, when b ring does not exist, Z, M, Q also do not exist; When a, b ring exists and Z, Q, M are all C, A
2be positioned at X
2ortho position or contraposition; When a ring presence or absence, b ring exists and Z, M are C, Q when being N, X
2be positioned at ortho position or the contraposition of Q on b ring; When a ring presence or absence, b ring exist and Z be C, Q, M is when being N, or when a ring presence or absence, b ring exists and Z, Q are N, M when being C, X
2be positioned at optional position on b ring;
Situation two: as halides A
1-R
1-X
1, A
2-R
2-X
2in R
1, R
2during for aryl, A
1-R
1-X
1, A
2-R
2-X
2be respectively the monocyclic aromatic compounds shown in general formula III, IV, or be respectively the bicyclic aromatic compounds shown in general formula V, VI:
In general formula III, IV:
When Z, Q, M are all C, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group or sulfonate group, A
1, A
2lay respectively at X
1or X
2ortho position or contraposition;
When Z be N, Q, M be C time, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, on pyridine ring 2 or 4; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
When Z, Q be N, M are C, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, two or three-digit on aromatic nucleus; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
When Z be C, Q, M be N time, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, optional position on aromatic nucleus; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
In general formula V, VI:
When Z, Q, M are all C, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group or sulfonate group, and A
1, A
2lay respectively at X
1or X
2ortho position or contraposition;
When Z be N, Q, M be C time, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, be positioned at 2 or 4 of quinoline ring; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
When Z, Q be N, M are C, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, be positioned at the two or three-digit of quinoxaline ring; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl;
When Z be C, Q, M be N time, X
1, X
2for halogen or trifluoromethanesulfonic acid ester group, position is at 2 or 4 of benzo pyrimidine ring; A
1, A
2for trifluoromethyl, trichloromethyl, trisbromomethyl, aldehyde radical, ethanoyl, nitro, cyano group, ester group, sulfonate group, methoxyl group, hydroxyl, hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, phenyl or benzyl.
2. the preparation method of a kind of thioether as claimed in claim 1, it is characterized in that, solvent in described formula (1), formula (2) is selected from toluene, tetrahydrofuran (THF), 1, one in 4-dioxane, N, N-dicarboximide, dimethyl sulfoxide (DMSO), methylene dichloride, acetonitrile, ether, methyl alcohol or ethanol.
3. the preparation method of a kind of thioether as claimed in claim 1, is characterized in that, the sulfide in described formula (1) is selected from M
2s, MSCN or MSCSOR, wherein, M is selected from lithium, sodium, potassium or caesium, and R is selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-or the tertiary butyl.
4. the preparation method of a kind of thioether as claimed in claim 1, is characterized in that, the elemental sulfur in described formula (2) is selected from S
2, S
4, S
6, S
8or the one in amorphous sulfur.
5. the preparation method of a kind of thioether as claimed in claim 1, is characterized in that, in described formula (2), the general formula of alkali is MOR or MY, and wherein, M is selected from lithium, sodium, potassium or caesium; R is selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl or carbonyl; Y is selected from carbonate, phosphate radical, acetate moiety, propionate, butanic acid root, methacrylate, positive pentanoate, isovalerate or PIVALIC ACID CRUDE (25) root.
6. the preparation method of a kind of thioether as claimed in claim 1, is characterized in that, the temperature of reaction of described formula (1), formula (2) is 20 ~ 180 DEG C.
7. the preparation method of a kind of thioether as claimed in claim 1, is characterized in that, X in described situation one
1, X
2for fluorine, chlorine, bromine or iodine.
8. the preparation method of a kind of thioether as claimed in claim 1, is characterized in that, X in described situation two
1, X
2for fluorine, chlorine, bromine or iodine.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111559976A (en) * | 2020-05-29 | 2020-08-21 | 扬州大学 | Synthetic method of heteroaryl thioether |
| CN115160196A (en) * | 2022-06-30 | 2022-10-11 | 浙江大学衢州研究院 | Preparation method of symmetrical thioether compound |
| CN115785023A (en) * | 2022-12-06 | 2023-03-14 | 天津久日新材料股份有限公司 | Preparation method of photoinitiator, product and application thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0524781A1 (en) * | 1991-07-25 | 1993-01-27 | Zeneca Limited | Therapeutic amides |
| JP2003146964A (en) * | 2001-11-15 | 2003-05-21 | New Japan Chem Co Ltd | Method for producing diarylsulfone polycarboxylic acid or its anhydride |
| WO2006038741A1 (en) * | 2004-10-08 | 2006-04-13 | Banyu Pharmaceutical Co., Ltd | Method for producing thioether compound |
| CN101962366A (en) * | 2010-09-15 | 2011-02-02 | 北京理工大学 | Diphenyl thioether linked bis-imidazoline ligand compound and preparation method thereof |
| CN102702511A (en) * | 2012-06-13 | 2012-10-03 | 四川大学 | Semi-aromatic polyphenyl sulfoether amide and preparation method of semi-aromatic polyphenyl sulfoether amide |
| CN103073463A (en) * | 2013-02-06 | 2013-05-01 | 西北师范大学 | Synthetic method of diaryl thioether |
| CN103787802A (en) * | 2014-02-11 | 2014-05-14 | 华东师范大学 | Aryl alkyl thioether compounds and synthesis method thereof |
| CN104629053A (en) * | 2013-11-12 | 2015-05-20 | 江苏扬农化工集团有限公司 | Preparation method of polyphenylene sulfide |
-
2015
- 2015-10-01 CN CN201510640231.3A patent/CN105218418A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0524781A1 (en) * | 1991-07-25 | 1993-01-27 | Zeneca Limited | Therapeutic amides |
| JP2003146964A (en) * | 2001-11-15 | 2003-05-21 | New Japan Chem Co Ltd | Method for producing diarylsulfone polycarboxylic acid or its anhydride |
| WO2006038741A1 (en) * | 2004-10-08 | 2006-04-13 | Banyu Pharmaceutical Co., Ltd | Method for producing thioether compound |
| CN101962366A (en) * | 2010-09-15 | 2011-02-02 | 北京理工大学 | Diphenyl thioether linked bis-imidazoline ligand compound and preparation method thereof |
| CN102702511A (en) * | 2012-06-13 | 2012-10-03 | 四川大学 | Semi-aromatic polyphenyl sulfoether amide and preparation method of semi-aromatic polyphenyl sulfoether amide |
| CN103073463A (en) * | 2013-02-06 | 2013-05-01 | 西北师范大学 | Synthetic method of diaryl thioether |
| CN104629053A (en) * | 2013-11-12 | 2015-05-20 | 江苏扬农化工集团有限公司 | Preparation method of polyphenylene sulfide |
| CN103787802A (en) * | 2014-02-11 | 2014-05-14 | 华东师范大学 | Aryl alkyl thioether compounds and synthesis method thereof |
Non-Patent Citations (6)
| Title |
|---|
| ANNENKOVA, V. Z.等: "Formation of radical anions and radicals in the reaction of sodium sulfide with haloaromatic compounds", 《ZHURNAL ORGANICHESKOI KHIMII》 * |
| HSING-YING CHEN 等: "Use of Base Control To Provide High Selectivity between Diaryl Thioether and Diaryl Disulfide for C−S Coupling Reactions of Aryl Halides and Sulfur and a Mechanistic Study", 《ORGANOMETALLICS》 * |
| PILYUGIN, V. S.等: "Synthesis and fungicidal activity of bis[2-[(arylcarbonyl)amino]-1H-benzimidazol-5-yl] sulfones", 《RUSSIAN JOURNAL OF GENERAL CHEMISTRY》 * |
| PLAKHTINSKII, V. V.等: "Synthesis of diarylenes from activated nitro- or haloaromatic compounds and sodium sulfide", 《IZVESTIYA VYSSHIKH UCHEBNYKH ZAVEDENII, KHIMIYA I KHIMICHESKAYATEKHNOLOGIYA》 * |
| 何庆 等: "2,5-二甲氧基-4-氯硝基苯与硫化钠的反应", 《有机化学》 * |
| 石开丁: "常温合成二正辛基亚砜", 《天津化工》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111559976A (en) * | 2020-05-29 | 2020-08-21 | 扬州大学 | Synthetic method of heteroaryl thioether |
| CN115160196A (en) * | 2022-06-30 | 2022-10-11 | 浙江大学衢州研究院 | Preparation method of symmetrical thioether compound |
| CN115160196B (en) * | 2022-06-30 | 2023-12-29 | 浙江大学衢州研究院 | Preparation method of symmetrical thioether compound |
| CN115785023A (en) * | 2022-12-06 | 2023-03-14 | 天津久日新材料股份有限公司 | Preparation method of photoinitiator, product and application thereof |
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