CN105924425B - A kind of method for preparing dihydro sulphur chroman derivative - Google Patents
A kind of method for preparing dihydro sulphur chroman derivative Download PDFInfo
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- CN105924425B CN105924425B CN201610286430.3A CN201610286430A CN105924425B CN 105924425 B CN105924425 B CN 105924425B CN 201610286430 A CN201610286430 A CN 201610286430A CN 105924425 B CN105924425 B CN 105924425B
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- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
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Abstract
The invention discloses a kind of methods for preparing dihydro sulphur chroman derivative, comprise the following steps：Under the conditions of existing for HMPA, using allylic bromination samarium as reducing agent, β arylthio ketone occurs to be coupled cyclization in THF, and reaction terminates the dihydro sulphur chroman derivative described in post-treated obtain.What this method realized thiophenyl using allylic bromination samarium for the first time efficiently removes aromatization reaction, without utilizing gem-dimethyl effect, you can realize that the α positions of S are unsubstituted and have the synthesis of various mono-substituted dihydro sulphur chromans high cis-selectivity.Synthesized dihydro sulphur chromanol can obtain sulphur chromanol through DDQ processing, such compound is tested through activity of weeding, and 85.8% is may be up to the inhibiting rate of the growth of Amaranthus retroflexus root, close to the positive control inhibiting rate of 2,4 D.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular to a kind of method for preparing dihydro sulphur chroman derivative.
Background technology
The synthesis of sulphur chroman and its derivative and its pharmaceutical activity research cause the attention in pesticide and medical research field.
Such as thiochromanone class compound have extensive physiological activity, to Cryptococcus neoformans, saccharomycete, microspore silk bacterium, mould and
Several important pathogeny bacterium such as trichophyta have stronger inhibitory activity.
Although the research for synthesizing sulphur chroman derivative is more, the report of synthesizing dihydro sulphur chroman is more rare so far.Dihydro
Sulphur chromanol can be oxidized to sulfone, sulfoxide (Synlett 2013,24,177-180) through metachloroperbenzoic acid (mCPBA), also may be used
To be oxidized to benzimidazole thiophanate chromanol (Scheme 1) by dichlorocyanobenzoquinone (DDQ).Thus this kind of chroman derivative can be
It prepares sulfone, sulfoxide and benzimidazole thiophanate chromanol and compound precursor is provided, or the screening of physiologically active compound provides new
Compound library.
2013, Ressig seminars reported carbonyl-aromatic ring coupling reaction to β-thio ketone with samarium diodide, to obtain
Obtain dihydro sulphur chroman compound (Synlett 2013,24,177-180).But product only has two, and product types are confined to
There is gem-dimethyl on the alpha-position of S, i.e., need to utilize gem-dimethyl effect, and have the isomer generation of double-bond positional isomerization
(Scheme 2).And β-thio ketone without gem-dimethyl substitution is only capable of providing the dihydro sulphur chromanol (Scheme 3) of 8% yield.
The content of the invention
The present invention provides a kind of universal methods for preparing dihydro sulphur chroman derivative, have not only widened the scope of substrate,
Various substituted dihydro sulphur chroman derivatives can be synthesized, while improve the yield of dihydro sulphur chroman.The configuration of product has
High cis-selectivity, and generated without the isomer by-product of double-bond isomerism.
A kind of method for preparing dihydro sulphur chroman derivative, comprises the following steps：
Under the conditions of hexamethyl phosphoramide (HMPA) is existing, using allylic bromination samarium as reducing agent, β-arylthio ketone exists
Coupling cyclization occurs in organic solvent, after reaction, the dihydro sulphur chroman derivative is obtained by post processing；
The structure of the β-arylthio ketone, allylic bromination samarium and dihydro sulphur chroman derivative respectively as Formulas I, II and
Shown in III：
In Formulas I and III, R1Independently selected from C1~C5Alkyl, substitution either unsubstituted phenyl, substitution or unsubstituted
Furyl；
R2Independently selected from the C arbitrarily substituted1~C5Alkyl, C1~C5Alkoxy or halogen；
R3Independently selected from H or C1~C5Alkyl, R4Independently selected from C1~C5Aliphatic alkyl or R4、R3With connect it
Group form five-membered ring (such as cyclopenta) or hexatomic ring (cyclohexyl).
The present invention realizes that the efficient of thiophenyl removes aromatization reaction using allylic bromination samarium for the first time, without using together with two
Methyl effect, you can realize the synthesis of the unsubstituted and substituted dihydro sulphur chroman of the alpha-position of S, substituent group can be a variety of
The alkyl and aryl of structure enrich the structure type of product.It is worth noting that use the method for the present invention, the alpha-position of sulphur
Unsubstituted dihydro sulphur chroman yield is up to 70%, and literature method (Synlett 2013,24,177-180) yield is only
8%.
Preferably, the R1For methyl, ethyl, phenyl, 2- furyls, the R2For methyl, methoxyl group, chlorine,
Bromine, the R3For H, methyl, the R4For methyl, ethyl, propyl.
The organic solvent is ether solvent, preferably, the organic solvent is tetrahydrofuran, at this point, reaction yield
Highest.
In the present invention, the ratio between amount of substance of the β-arylthio ketone and allylic bromination samarium is 1.0：2.0~2.5.
Preferably, reaction concrete operations are：Under nitrogen protection, it is samarium powder and allyl bromide, bromoallylene is in situ in tetrahydrofuran
The allylic bromination samarium solution is obtained by the reaction, then by HMPA add in allylic bromination samarium solution and be cooled to -30 DEG C with
Under, then the tetrahydrofuran solution of β-arylthio ketone is added in and carries out reduction reaction.
Preferably, the post processing includes：The aqueous sodium potassium tartrate of saturation, reaction solution are added in into reaction solution
Room temperature gradually is gone back up to, is extracted with ethyl acetate, obtained organic phase is washed, dried, concentrated and column chromatography, obtains described
Dihydro sulphur chroman derivative.
Compared with prior art, advantages of the present invention is mainly reflected in：
(1) using organic samarium as coupling reagent aromatization is removed realize alkylthio group substitution aromatic ring, reaction condition is mild,
Reaction time is short, high income；
(2) various structures of product dihydro sulphur chroman can be that the α positions of S have various substituent groups, can also be unsubstituted, and
It need not be confined to must have gem-dimethyl substitution, so as to provide new compound library for the screening of physiologically active compound.
Description of the drawings
Fig. 1 is the product of embodiment 11H NMR spectras；
Fig. 2 is the product of embodiment 113C NMR spectras.
Specific embodiment
Below with specific embodiment come the technical solution that further illustrates the present invention, but the scope of application of the present invention not office
It is limited to following instance.Following product passes through1H NMR and13C NMR confirm.
Embodiment 1：
4-methyl-2-phenyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(IIIa)
4- methyl -2- phenyl-trans- 3,4,4 α, the preparation of 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- phenyl -4- (thiophenyl) -2- butyl- ketone：Allylic bromination samarium=1.0：2.5, wherein
4- phenyl -4- (thiophenyl) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage 30mL, toward pi-allyl at -30 DEG C
The tetrahydrofuran solution of 4- phenyl -4- (thiophenyl) butyl- 2- ketone is injected in the tetrahydrofuran solution of samaric bromide, is reacted 30 minutes.
Under nitrogen protection, samarium powder and allyl bromide, bromoallylene are stirred to react at room temperature in tetrahydrofuran 1 it is small when, generate allyl
HMPA is then added in reaction system with syringe, and the temperature of reaction system is reduced to -30 DEG C by base samaric bromide.Then will
The tetrahydrofuran solution of β-arylthio ketone adds in above-mentioned reaction system by syringe, and TLC tracks to raw material, and the reaction was complete.To anti-
It answers and saturation sodium potassium tartrate solution (20ml) is added in mixture, reaction solution gradually goes back up to room temperature, is extracted with ethyl acetate
(20ml × 3), organic phase are washed successively with saturated sodium bicarbonate sodium solution (20ml), dilute hydrochloric acid (20ml) saturated salt solution (20ml)
It washs, anhydrous Na2SO4It is dry.Concentration, gained crude product is through silica gel column chromatography separating purification (solvent：EtOAc/Petrol=1：30
~1：20) product 4- methyl -2- phenyl-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol, yield 78%, are obtained.Product table
It is as follows to levy data：1H NMR(600MHz,CDCl3) δ 7.41 (d, J=7.5Hz, 2H), 7.36 (t, J=7.6Hz, 2H), 7.31-
7.29 (m, 1H), 6.15-6.13 (m, 1H), 6.03-6.01 (m, 1H), 5.92-5.90 (m, 1H), 4.15 (dd, J=12.4,
2.9Hz, 1H), 3.13 (t, J=7.1Hz, 1H), 2.86-2.74 (m, 2H), 2.37 (t, J=12.6Hz, 1H), 2.29 (dd, J
=12.8,2.9Hz, 1H), 1.22 (s, 3H)13C NMR(100MHz,CDCl3)δ140.4,130.6,128.7,127.8,
127.6,126.8,125.2,123.6,73.6,50.4,49.8,45.9,28.0,21.8.
Application examples 1
The dihydro sulphur chromanol 0.2mmol that embodiment 1 is obtained, ethyl acetate 2ml, DDQ0.24mmol are in 25ml round bottoms
30min is stirred in flask at room temperature, reaction system is evaporated under reduced pressure to concentration on a rotary evaporator, gained crude product is through silica gel
Column chromatographic isolation and purification, the yield to be higher than 99% obtains benzimidazole thiophanate chroman alcoholic compound, shown in structure such as formula (IV a)：
Test that (method, which is shown in, should iron, Yin Caiping, leaf sage's great waves etc., cotton locust enteron aisle fungi Phoma sp.HCO through activity of weeding3
Weeding and immunosuppressant ingredient research,《Research and development of natural products》, 2010,22,600-602.), the alcoholization of benzimidazole thiophanate chroman
Closing object has the growth of Amaranthus retroflexus root 72.4% inhibiting rate.
Embodiment 2：
2-(4-chlorophenyl)-4-methyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol
(IIIb) preparation of 4- methyl -2- (4- chlorphenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (4- chlorphenyls) -4- (thiophenyl) -2- butanone：Allylic bromination samarium=1.0：2.5
Wherein 4- (4- chlorphenyls) -4- (thiophenyl) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage 30mL, in -30 DEG C
The lower tetrahydrofuran that 4- (4- chlorphenyls) -4- (thiophenyl) 2- butyl- ketone is injected into the tetrahydrofuran solution of allylic bromination samarium
Solution reacts 30 minutes.
The other the same as in Example 1 obtains 4- methyl -2- (4- chlorphenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chromans -4-
Alcohol, yield 59%.
Embodiment 3：
2-(2-chlorophenyl)-4-methyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol
(IIIc)
The preparation of 4- methyl -2- (2- chlorphenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (2- chlorphenyls) -4- (thiophenyl) -2- butanone：Allylic bromination samarium=1.0：2.5
Wherein 4- (2- chlorphenyls) -4- (thiophenyl) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage 30mL, in -30 DEG C
The lower tetrahydrofuran that 4- (2- chlorphenyls) -4- (thiophenyl) -2- butanone is injected into the tetrahydrofuran solution of allylic bromination samarium
Solution reacts 30 minutes.
The other the same as in Example 1 obtains 4- methyl -2- (2- chlorphenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chromans -4-
Alcohol, yield 53%.
Embodiment 4：
2-(4-bromophenyl)-4-methyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol
(IIId)
The preparation of 4- methyl -2- (4- bromophenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol.
Feed intake substance amount ratio be 4- (4- bromophenyls) -4- (thiophenyl) -2- butanone：Allylic bromination samarium=1.0：2.0
Wherein 4- (4- bromophenyls) -4- (thiophenyl) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage 30mL, in -30 DEG C
The lower tetrahydrofuran that 4- (4- bromophenyls) -4- (thiophenyl) -2- butyl- ketone is injected into the tetrahydrofuran solution of allylic bromination samarium
Solution reacts 30 minutes.
The other the same as in Example 1 obtains 4- methyl -2- (4- bromophenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chromans -4-
Alcohol, yield 66%.
Embodiment 5：
2-(3-bromophenyl)-4-methyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol
(IIIe)
The preparation of 4- methyl -2- (3- bromophenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (3- bromophenyls) -4- (thiophenyl) -2- butanone：Allylic bromination samarium=1.0：2.0
Wherein 4- (3- bromophenyls) -4- (thiophenyl) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage 30mL, in -30 DEG C
The lower tetrahydrofuran that 4- (3- bromophenyls) -4- (thiophenyl) -2- butanone is injected into the tetrahydrofuran solution of allylic bromination samarium
Solution reacts 30 minutes.
The other the same as in Example 1 obtains 4- methyl -2- (3- bromophenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chromans -4-
Alcohol, yield 64%.
Embodiment 6：
4-methyl-2-(4-(trifluoromethyl)phenyl)-3,4,4a,7-tetrahydro-2H-
thiochromen-4-ol(IIIf)
The preparation of 4- methyl -2- (4- trifluoromethyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (4- trifluoromethyls) -4- (thiophenyl) -2- butanone：Allylic bromination samarium=
1.0：2.5, wherein 4- (4- trifluoromethyls) -4- (thiophenyl) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage
For 30mL, 4- (4- trifluoromethyls) -4- (benzene sulphur is injected into the tetrahydrofuran solution of allylic bromination samarium at -30 DEG C
Base) -2- butanone tetrahydrofuran solution, react 30 minutes.
The other the same as in Example 1 obtains 4- methyl -2- (4- trifluoromethyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur colors
Full -4- alcohol, yield 69%.
Application examples 2
The dihydro sulphur chromanol product 0.2mmol that embodiment 6 is obtained, ethyl acetate 2ml, DDQ0.24mmol is in 25ml
30min is stirred in round-bottomed flask at room temperature, reaction system is evaporated under reduced pressure to concentration, gained crude product warp on a rotary evaporator
Silica gel column chromatography separating purification, the yield to be higher than 99% obtains benzimidazole thiophanate chroman alcoholic compound, shown in structure such as formula (V b of I)：
It is tested through activity of weeding, which has the growth of Amaranthus retroflexus root 85.8% inhibiting rate, the positive with 2,4-D
It is suitable to compare inhibiting rate 88.9%.
Embodiment 7：
2-(4-methoxyphenyl)-4-methyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol
(IIIg)
The preparation of 4- methyl -2- (4- methoxyphenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (4- methoxyphenyls) -4- (thiophenyl) -2- butanone：Allylic bromination samarium=1.0：
2.5, wherein 4- (4- methoxyphenyls) -4- (thiophenyl) -2- butanone 1mmol, organic solvent is tetrahydrofuran, and dosage is
30mL, at -30 DEG C into the tetrahydrofuran solution of allylic bromination samarium inject 4- (4- methoxyphenyls) -4- (thiophenyl) -
The tetrahydrofuran solution of 2- butanone reacts 30 minutes.
The other the same as in Example 1, obtains 4- methyl -2- (4- methoxyphenyls)-trans- 3,4,4 α, and 7- tetrahydrochysene -2H- sulphur chroman -
4- alcohol, yield 62%.
Embodiment 8：
4,6-dimethyl-2-phenyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(IIIh)
4,6- dimethyl -2- phenyl-trans- 3,4,4 α, the preparation of 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- phenyl -4- (p-methylphenyl is thio) -2- butanone：Allylic bromination samarium=1.0：2.5
Wherein 4- phenyl -4- (p-methylphenyl is thio) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage 30mL, in -30 DEG C
The lower tetrahydrofuran that 4- phenyl -4- (p-methylphenyl is thio) -2- butanone is injected into the tetrahydrofuran solution of allylic bromination samarium
Solution reacts 30 minutes.
The other the same as in Example 1, obtains 4,6- dimethyl -2- phenyl-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol,
Yield 66%.
Embodiment 9：
2-(4-methoxyphenyl)-4,6-dimethyl-3,4,4a,7-tetrahydro-2H-thiochromen-
4-ol(IIIi)
The preparation of 4,6- dimethyl -2- (4- methoxyphenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (4- methoxyphenyls) -4- (p-methylphenyl is thio) -2- butanone：Allylic bromination samarium
=1.0：2.5, wherein 4- (4- methoxyphenyls) -4- (p-methylphenyl is thio) -2- butanone 1mmol, organic solvent are tetrahydrochysene furan
It mutters, dosage 30mL injects 4- (4- methoxyphenyls) -4- at -30 DEG C into the tetrahydrofuran solution of allylic bromination samarium
The tetrahydrofuran solution of (p-methylphenyl is thio) -2- butanone reacts 30 minutes.
The other the same as in Example 1 obtains 4,6- dimethyl -2- (4- methoxyphenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur
Chroman -4- alcohol, yield 64%.
Embodiment 10：
2-(4-bromophenyl)-4,6-dimethyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-
ol(IIIj)
The preparation of 4,6- dimethyl -2- (4- bromophenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (4- bromophenyls) -4- (p-methylphenyl is thio) -2- butanone：Allylic bromination samarium=
1.0：2.5, wherein 4- (4- bromophenyls) -4- (p-methylphenyl is thio) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage
For 30mL, 4- (4- bromophenyls) -4- (p-methylphenyl sulphur is injected into the tetrahydrofuran solution of allylic bromination samarium at -30 DEG C
Generation) -2- butanone tetrahydrofuran solution, react 30 minutes.
The other the same as in Example 1, obtains 4,6- dimethyl -2- (4- bromophenyls)-trans- 3,4,4 α, and 7- tetrahydrochysene -2H- sulphur chroman -
4- alcohol, yield 67%.
Embodiment 11：
2-(3-bromophenyl)-4,6-dimethyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-
ol(IIIk)
The preparation of 4,6- dimethyl -2- (3- bromophenyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (3- bromophenyls) -4- (p-methylphenyl is thio) -2- butanone：Allylic bromination samarium=
1.0：2.5, wherein 4- (3- bromophenyls) -4- (p-methylphenyl is thio) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage
For 30mL, 4- (3- bromophenyls) -4- (p-methylphenyl sulphur is injected into the tetrahydrofuran solution of allylic bromination samarium at -30 DEG C
Generation) -2- butanone tetrahydrofuran solution, react 30 minutes.
The other the same as in Example 1, obtains 4,6- dimethyl -2- (3- bromophenyls)-trans- 3,4,4 α, and 7- tetrahydrochysene -2H- sulphur chroman -
4- alcohol, yield 63%.
Embodiment 12：
8-bromo-2-(2-chlorophenyl)-4-methyl-3,4,4a,7-tetrahydro-2H-thiochrome
n-4-ol(IIIl)
The preparation of the bromo- 2- of 4- methyl -8- (2- chlorphenyls)-trans- 3,4,4 α, 5- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- ((2- bromophenyls) sulfenyl) -4- (2- chlorphenyls) -2- butanone：Allylic bromination samarium=
1.0：2.5, wherein 4- ((2- bromophenyls) sulfenyl) -4- (2- chlorphenyls) -2- butanone 1mmol, organic solvent is tetrahydrofuran, is used
It measures as 30mL, injects 4- ((2- bromophenyls) sulfenyl) -4- (2- into the tetrahydrofuran solution of allylic bromination samarium at -30 DEG C
Chlorphenyl) -2- butanone tetrahydrofuran solution, react 30 minutes.
The other the same as in Example 1 obtains the bromo- 2- of 4- methyl -8- (2- chlorphenyls)-trans- 3,4,4 α, 5- tetrahydrochysene -2H- sulphur colors
Full -4- alcohol, yield 53%.
Embodiment 13：
2-(furan-2-yl)-4-methyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(IIIm)
The preparation of 4- methyl -2- (2- furyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (2- furyls) -4- (thiophenyl) -2- butanone：Allylic bromination samarium=1.0：2.5
Wherein 4- (2- furyls) -4- (thiophenyl) -2- butanone 1mmol, organic solvent are tetrahydrofuran, dosage 30mL, in -30 DEG C
The lower tetrahydrofuran that 4- (2- furyls) -4- (thiophenyl) -2- butanone is injected into the tetrahydrofuran solution of allylic bromination samarium
Solution reacts 30 minutes.
The other the same as in Example 1 obtains 4- methyl -2- (2- furyls)-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chromans -4-
Alcohol, yield 79%.
Embodiment 14：
2,4-dimethyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(III n)
The preparation of 2,4- dimethyl-trans- 3,4,4a, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 4- (thiophenyl) -2 pentanone：Allylic bromination samarium=1.0：2.5, wherein 4- (benzene sulphur
Base) -2 pentanone 1mmol, organic solvent is tetrahydrofuran, dosage 30mL, toward the tetrahydrochysene furan of allylic bromination samarium at -30 DEG C
It mutters and the tetrahydrofuran solution of 4- (thiophenyl) -2 pentanone is injected in solution, react 30 minutes.
The other the same as in Example 1 obtains 2,4- dimethyl-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol, yield 83%
Embodiment 15：
4-ethyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(IIIo)
4- ethyls-trans- 3,4,4 α, the preparation of 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol
Feed intake substance amount ratio be 1- (thiophenyl)-propione：Allylic bromination samarium=1.0：2.5, wherein 1- (benzene sulphur
Base)-propione 1mmol, organic solvent is tetrahydrofuran, dosage 30mL, toward the tetrahydrochysene furan of allylic bromination samarium at -30 DEG C
It mutters and the tetrahydrofuran solution of 1- (thiophenyl)-propione is injected in solution, react 30 minutes.
The other the same as in Example 1 obtains 4- ethyls-trans- 3,4,4 α, 7- tetrahydrochysene -2H- sulphur chroman -4- alcohol, yield 80%.
Claims (9)
- A kind of 1. method for preparing dihydro sulphur chroman derivative, which is characterized in that comprise the following steps：Under the conditions of existing for hexamethyl phosphoramide, using allylic bromination samarium as reducing agent, β-arylthio ketone is in organic solvent Generation coupling cyclisation, reaction terminates, post-treated to obtain the dihydro sulphur chroman derivative；The structure of the β-arylthio ketone, allylic bromination samarium and dihydro sulphur chroman derivative are respectively such as Formulas I, II and III institutes Show：In Formulas I and III, R1Independently selected from C1~C5Alkyl, phenyl, furyl；R2Independently selected from C1~C5Alkyl, C1~C5Alkoxy or halogen；R3Independently selected from H or C1~C5Alkyl, R4Independently selected from C1~C5Aliphatic alkyl or R4、R3With connect theirs Group forms five-membered ring or hexatomic ring.
- 2. the method according to claim 1 for preparing dihydro sulphur chroman derivative, which is characterized in that the R1For methyl, Ethyl, phenyl or 2- furyls.
- 3. the method according to claim 1 for preparing dihydro sulphur chroman derivative, which is characterized in that the R2For methyl, Methoxyl group, chlorine or bromine.
- 4. the method according to claim 1 for preparing dihydro sulphur chroman derivative, which is characterized in that the R3For H or first Base.
- 5. the method according to claim 1 for preparing dihydro sulphur chroman derivative, which is characterized in that the R4For methyl, Ethyl or propyl.
- 6. the method according to claim 1 for preparing dihydro sulphur chroman derivative, which is characterized in that the organic solvent is Tetrahydrofuran.
- 7. the method according to claim 1 for preparing dihydro sulphur chroman derivative, which is characterized in that the β-arylthio The ratio between amount of substance of ketone and allylic bromination samarium is 1.0：2.0~2.5.
- 8. the method according to claim 1 for preparing dihydro sulphur chroman derivative, which is characterized in that reaction concrete operations For：Under nitrogen protection, it is molten that samarium powder and allyl bromide, bromoallylene are obtained by the reaction to the allylic bromination samarium in situ in tetrahydrofuran Then hexamethyl phosphoramide is added in allylic bromination samarium solution and is cooled to less than -30 DEG C, then four by β-arylthio ketone by liquid The addition of hydrogen tetrahydrofuran solution carries out coupling cyclization.
- 9. the method according to claim 1 for preparing dihydro sulphur chroman derivative, which is characterized in that the post processing bag It includes：The aqueous sodium potassium tartrate of saturation is added in into reaction solution, reaction solution gradually goes back up to room temperature, is extracted with ethyl acetate, Obtained organic phase is washed, dried, concentrated and column chromatography, obtains the dihydro sulphur chroman derivative.
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