CN105924425A - Preparation method of dihydrothiochroman derivative - Google Patents

Preparation method of dihydrothiochroman derivative Download PDF

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CN105924425A
CN105924425A CN201610286430.3A CN201610286430A CN105924425A CN 105924425 A CN105924425 A CN 105924425A CN 201610286430 A CN201610286430 A CN 201610286430A CN 105924425 A CN105924425 A CN 105924425A
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sulfur
samarium
chroman derivative
method preparing
methyl
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CN105924425B (en
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王小霞
谢婷婷
李建永
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Zhejiang Normal University CJNU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—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
    • 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
    • A01N43/14—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 six-membered rings
    • A01N43/18—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 six-membered rings with sulfur as the ring hetero atom

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Abstract

The invention discloses a method for preparing a dihydrothiochroman derivative. The method comprises the following steps: under the existence of HMPA, allyl samarium bromide is adopted as a reducing agent, and beta-arylthio ketone is subjected to a coupling cyclization reaction in THF; a treatment is carried out after the reaction, and the dihydrothiochroman derivative is obtained. According to the invention, a phenylthio high-efficiency de-aromatization reaction is realized with allyl samarium bromide for a first time. No gem-dimethyl effect is needed, and dihydrothiochroman synthesis with no substitution on the alpha-site of S and with various single substitutions can be realized with high diastereoselectivity. After a DDQ treatment of the synthesized dihydrothiochromanol, thiochromanol can be obtained. As a result of a herbicidal activity test, the compound has an amaranthus retroflexus root growth inhibition rate up to 85.8%, which is close to a 2,4-D positive control inhibition rate.

Description

A kind of method preparing dihydro sulfur chroman derivative
Technical field
The invention belongs to organic synthesis field, be specifically related to a kind of side preparing dihydro sulfur chroman derivative Method.
Background technology
Sulfur chromane and the synthesis of derivant and pharmaceutically active research thereof thereof cause pesticide and medical research The attention in field.Such as thiochromanone compounds has physiologically active widely, to Cryptococcus histolyticus, Several important source of disease bacterium such as yeast, sporidiole silk bacterium, mycete and trichophyton have stronger suppression Activity.
Although the research of synthesis sulfur chroman derivative is more, the report of synthesizing dihydro sulfur chromane is the most more Rare.Dihydro sulfur chromane alcohol can be oxidized to sulfone, sulfoxide (Synlett through metachloroperbenzoic acid (mCPBA) 2013,24,177-180), it is also possible to be oxidized to benzimidazole thiophanate chromane by DDQ (DDQ) Alcohol (Scheme 1).Thus this kind of chroman derivative can be to prepare sulfone, sulfoxide and benzimidazole thiophanate chromane Alcohol provides compound precursor, it is also possible to for the compound library that the screening offer of physiologically active compound is new.
2013, Ressig seminar reported with samarium diodide even for the carbonyl-aromatic ring of ketone to β-sulfur Connection reaction, obtains dihydro sulfur chroman compound (Synlett 2013,24,177-180).But product only has Two examples, and product types is confined to have gem-dimethyl on the alpha-position of S, i.e. needs to utilize gem-dimethyl to imitate Should, and have the isomer generation (Scheme 2) of double-bond positional isomerization.And replace without gem-dimethyl β-sulfur be only capable of providing dihydro sulfur chromane alcohol (Scheme 3) of 8% productivity for ketone.
Summary of the invention
The invention provides a kind of universal method preparing dihydro sulfur chroman derivative, not only widened at the end The scope of thing, can synthesize various substituted dihydro sulfur chroman derivative, improve dihydro sulfur color simultaneously Full yield.The configuration of product has high cis-selectivity, and does not has the isomerism of double-bond isomerism Body by-product generates.
A kind of method preparing dihydro sulfur chroman derivative, comprises the following steps:
Under conditions of hexamethyl phosphoramide (HMPA) exists, with allylic bromination samarium as reducing agent, There is coupling cyclization in β-arylthio ketone, after reaction terminates, obtains through post processing in organic solvent To described dihydro sulfur chroman derivative；
The structure of described β-arylthio ketone, allylic bromination samarium and dihydro sulfur chroman derivative is the most such as Shown in Formulas I, II and III:
In Formulas I and III, R1Independently selected from C1～C5Alkyl, replacement or unsubstituted phenyl, Replace or unsubstituted furyl；
R2Independently selected from any substituted C1～C5Alkyl, C1～C5Alkoxy or halogen；
R3Independently selected from H or C1～C5Alkyl, R4Independently selected from C1～C5Aliphatic alkyl, Or R4、R3Five-membered ring (such as cyclopenta) or hexatomic ring (ring is formed with the group connecting them Hexyl).
The present invention uses allylic bromination samarium efficiently to go aromatization reaction, nothing to realize thiophenyl first Must utilize gem-dimethyl effect, the alpha-position that can realize S is unsubstituted, and substituted dihydro sulfur color Full synthesis, substituent group can be alkyl and the aryl of various structures, enriches the structure type of product. It is worthy of note, the method using the present invention, the dihydro sulfur chromane productivity that the alpha-position of sulfur is unsubstituted can Reach 70%, and literature method (Synlett 2013,24,177-180) productivity is only 8%.
As preferably, described R1For methyl, ethyl, phenyl, 2-furyl, described R2For Methyl, methoxyl group, chlorine, bromine, described R3For H, methyl, described R4For methyl, ethyl, Propyl group.
Described organic solvent is ether solvent, and as preferably, described organic solvent is oxolane, this Time, reaction yield is the highest.
In the present invention, described β-arylthio ketone is 1.0 with the ratio of the amount of the material of allylic bromination samarium: 2.0～2.5.
As preferably, reaction concrete operations are: under nitrogen protection, by samarium powder and allyl bromide, bromoallylene in four The reaction of hydrogen furan situ obtains described allylic bromination samarium solution, then HMPA is added alkene Propyl group samaric bromide solution is also cooled to less than-30 DEG C, then is added by the tetrahydrofuran solution of β-arylthio ketone Enter to carry out reduction reaction.
As preferably, described post processing includes: add saturated potassium sodium tartrate water in reactant liquor Solution, reactant liquor gradually goes back up to room temperature, is extracted with ethyl acetate, the organic facies obtained carries out washing, It is dried, concentrates and column chromatography, obtain described dihydro sulfur chroman derivative.
Compared with prior art, advantages of the present invention is mainly reflected in:
(1) use organic samarium as coupling reagent realize alkylthio group replace aromatic ring remove aromatization, Reaction condition is gentle, the response time is short, yield is high；
(2) various structures of product dihydro sulfur chromane, can be that the α position of S has various substituent group, also Can be unsubstituted, without being confined to have gem-dimethyl to replace, such that it is able to be physiology active ingredient The screening of thing provides new compound library.
Accompanying drawing explanation
Fig. 1 is the product of embodiment 11H NMR spectra；
Fig. 2 is the product of embodiment 113C NMR spectra.
Detailed description of the invention
Further illustrate technical scheme with specific embodiment below, but the present invention's is applicable Scope is not limited to following instance.The equal warp of following product1H NMR and13C NMR confirms.
Embodiment 1:
4-methyl-2-phenyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(IIIa)
The preparation of 4-methyl-2-phenyl-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-phenyl-4-(thiophenyl)-2-butyl-ketone: allylic bromination samarium=1.0: 2.5, wherein 4-phenyl-4-(thiophenyl)-2-butanone 1mmol, organic solvent is oxolane, consumption For 30mL, at-30 DEG C, in the tetrahydrofuran solution of allylic bromination samarium, inject 4-phenyl-4-(benzene Sulfenyl) tetrahydrofuran solution of butyl-2-ketone, reacts 30 minutes.
Under nitrogen protection, samarium powder and allyl bromide, bromoallylene are stirred reaction 1 in oxolane under room temperature little Time, generate allylic bromination samarium, with syringe, HMPA added reaction system subsequently, and will be anti- The temperature answering system is reduced to-30 DEG C.Then the tetrahydrofuran solution of β-arylthio ketone is passed through syringe Adding above-mentioned reaction system, it is complete that TLC tracks to raw material reaction.Add saturated in reactant mixture Sodium potassium tartrate solution (20ml), reactant liquor gradually goes back up to room temperature, is extracted with ethyl acetate (20ml × 3), organic facies is successively with saturated sodium bicarbonate sodium solution (20ml), dilute hydrochloric acid (20ml) saturated food Saline (20ml) washs, anhydrous Na2SO4It is dried.Concentrating, gained crude product separates pure through silica gel column chromatography Change (developing solvent: EtOAc/Petrol=1:30～1:20), obtain product 4-methyl-2-phenyl-anti- -3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol, yield 78%.Characterization of The Products data are as follows: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 sulfur chromane alcohol 0.2mmol that embodiment 1 is obtained, ethyl acetate 2ml, DDQ 0.24mmol stirs 30min in 25ml round-bottomed flask under room temperature, reaction system rotated Reduce pressure on evaporimeter distillation and concentration, and gained crude product is through silica gel column chromatography separating purification, with higher than 99% Yield obtains benzimidazole thiophanate chromane alcoholic compound, shown in structure such as formula (IV a):
Through activity of weeding test, (method is shown in and should iron, Yin Caiping, leaf sage's great waves etc., cotton locust intestinal fungus Phoma sp.HCO3Weeding and immunosuppressant ingredient research, " research and development of natural products ", 2010, 22,600-602.), benzimidazole thiophanate chromane alcoholic compound has the suppression ratio of 72.4% to the growth of Amaranthus retroflexus root.
Embodiment 2:
2-(4-chlorophenyl)-4-methyl-3,4,4a, 7-tetrahydro-2H-thiochromen-4-ol (IIIb) 4-methyl The preparation of-2-(4-chlorphenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(4-chlorphenyl)-4-(thiophenyl)-2-butanone: allylic bromination samarium= 1.0:2.5, wherein 4-(4-chlorphenyl)-4-(thiophenyl)-2-butanone 1mmol, organic solvent is tetrahydrochysene Furan, consumption is 30mL, injects at-30 DEG C in the tetrahydrofuran solution of allylic bromination samarium The tetrahydrofuran solution of 4-(4-chlorphenyl)-4-(thiophenyl) 2-butyl-ketone, reacts 30 minutes.
The other the same as in Example 1, obtains 4-methyl-2-(4-chlorphenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur Chromane-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-chlorphenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(2-chlorphenyl)-4-(thiophenyl)-2-butanone: allylic bromination samarium= 1.0:2.5, wherein 4-(2-chlorphenyl)-4-(thiophenyl)-2-butanone 1mmol, organic solvent is tetrahydrochysene Furan, consumption is 30mL, injects at-30 DEG C in the tetrahydrofuran solution of allylic bromination samarium The tetrahydrofuran solution of 4-(2-chlorphenyl)-4-(thiophenyl)-2-butanone, reacts 30 minutes.
The other the same as in Example 1, obtains 4-methyl-2-(2-chlorphenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur Chromane-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-bromophenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol.
Feed intake the amount of material than for 4-(4-bromophenyl)-4-(thiophenyl)-2-butanone: allylic bromination samarium= 1.0:2.0, wherein 4-(4-bromophenyl)-4-(thiophenyl)-2-butanone 1mmol, organic solvent is tetrahydrochysene Furan, consumption is 30mL, injects at-30 DEG C in the tetrahydrofuran solution of allylic bromination samarium The tetrahydrofuran solution of 4-(4-bromophenyl)-4-(thiophenyl)-2-butyl-ketone, reacts 30 minutes.
The other the same as in Example 1, obtains 4-methyl-2-(4-bromophenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur Chromane-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-bromophenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(3-bromophenyl)-4-(thiophenyl)-2-butanone: allylic bromination samarium= 1.0:2.0, wherein 4-(3-bromophenyl)-4-(thiophenyl)-2-butanone 1mmol, organic solvent is tetrahydrochysene Furan, consumption is 30mL, injects at-30 DEG C in the tetrahydrofuran solution of allylic bromination samarium The tetrahydrofuran solution of 4-(3-bromophenyl)-4-(thiophenyl)-2-butanone, reacts 30 minutes.
The other the same as in Example 1, obtains 4-methyl-2-(3-bromophenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur colors Full-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-trifluoromethyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(4-trifluoromethyl)-4-(thiophenyl)-2-butanone: allyl bromide, bromoallylene Changing samarium=1.0:2.5, wherein 4-(4-trifluoromethyl)-4-(thiophenyl)-2-butanone 1mmol, has Machine solvent is oxolane, and consumption is 30mL, toward the tetrahydrochysene furan of allylic bromination samarium at-30 DEG C Mutter and solution injects the tetrahydrofuran solution of 4-(4-trifluoromethyl)-4-(thiophenyl)-2-butanone, instead Answer 30 minutes.
The other the same as in Example 1, obtains 4-methyl-2-(4-trifluoromethyl)-trans-3,4,4 α, 7-tetrahydrochysenes -2H-sulfur chromane-4-alcohol, yield 69%.
Application examples 2
The dihydro sulfur chromane alcohol product 0.2mmol that embodiment 6 is obtained, ethyl acetate 2ml, DDQ 0.24mmol stirs 30min in 25ml round-bottomed flask under room temperature, reaction system rotated Reduce pressure on evaporimeter distillation and concentration, and gained crude product is through silica gel column chromatography separating purification, with higher than 99% Yield obtains benzimidazole thiophanate chromane alcoholic compound, shown in structure such as formula (I V b):
Testing through activity of weeding, this compound has the suppression ratio of 85.8% to the growth of Amaranthus retroflexus root, with The positive control suppression ratio 88.9% of 2,4-D is suitable.
Embodiment 7:
2-(4-methoxyphenyl)-4-methyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(IIIg)
The preparation of 4-methyl-2-(4-methoxyphenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(4-methoxyphenyl)-4-(thiophenyl)-2-butanone: allylic bromination Samarium=1.0:2.5, wherein 4-(4-methoxyphenyl)-4-(thiophenyl)-2-butanone 1mmol, You Jirong Agent is oxolane, and consumption is 30mL, and at-30 DEG C, the oxolane toward allylic bromination samarium is molten Liquid injects the tetrahydrofuran solution of 4-(4-methoxyphenyl)-4-(thiophenyl)-2-butanone, reacts 30 points Clock.
The other the same as in Example 1, obtains 4-methyl-2-(4-methoxyphenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H- Sulfur chromane-4-alcohol, yield 62%.
Embodiment 8:
4,6-dimethyl-2-phenyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(IIIh)
The preparation of 4,6-dimethyl-2-phenyl-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-phenyl-4-(p-methylphenyl sulfur generation)-2-butanone: allylic bromination samarium= 1.0:2.5, wherein 4-phenyl-4-(p-methylphenyl sulfur generation)-2-butanone 1mmol, organic solvent is tetrahydrochysene Furan, consumption is 30mL, injects at-30 DEG C in the tetrahydrofuran solution of allylic bromination samarium The tetrahydrofuran solution of 4-phenyl-4-(p-methylphenyl sulfur generation)-2-butanone, 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-sulfur chromanes -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-methoxyphenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(4-methoxyphenyl)-4-(p-methylphenyl sulfur generation)-2-butanone: allyl Base samaric bromide=1.0:2.5, wherein 4-(4-methoxyphenyl)-4-(p-methylphenyl sulfur generation)-2-butanone 1 Mmol, organic solvent is oxolane, and consumption is 30mL, toward allylic bromination samarium at-30 DEG C Tetrahydrofuran solution in inject 4-(4-methoxyphenyl)-4-(p-methylphenyl sulfur generation)-2-butanone tetrahydrochysene Tetrahydrofuran solution, reacts 30 minutes.
The other the same as in Example 1, obtains 4,6-dimethyl-2-(4-methoxyphenyl)-trans-3,4,4 α, 7-tetra- Hydrogen-2H-sulfur chromane-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-bromophenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(4-bromophenyl)-4-(p-methylphenyl sulfur generation)-2-butanone: allyl bromide, bromoallylene Changing samarium=1.0:2.5, wherein 4-(4-bromophenyl)-4-(p-methylphenyl sulfur generation)-2-butanone 1mmol, has Machine solvent is oxolane, and consumption is 30mL, toward the tetrahydrochysene furan of allylic bromination samarium at-30 DEG C Mutter and solution injects the tetrahydrofuran solution of 4-(4-bromophenyl)-4-(p-methylphenyl sulfur generation)-2-butanone, instead Answer 30 minutes.
The other the same as in Example 1, obtains 4,6-dimethyl-2-(4-bromophenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H- Sulfur chromane-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-bromophenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(3-bromophenyl)-4-(p-methylphenyl sulfur generation)-2-butanone: allyl bromide, bromoallylene Changing samarium=1.0:2.5, wherein 4-(3-bromophenyl)-4-(p-methylphenyl sulfur generation)-2-butanone 1mmol, has Machine solvent is oxolane, and consumption is 30mL, toward the tetrahydrochysene furan of allylic bromination samarium at-30 DEG C Mutter and solution injects the tetrahydrofuran solution of 4-(3-bromophenyl)-4-(p-methylphenyl sulfur generation)-2-butanone, instead Answer 30 minutes.
The other the same as in Example 1, obtains 4,6-dimethyl-2-(3-bromophenyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H- Sulfur chromane-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-chlorphenyl)-trans-3,4,4 α, 5-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-((2-bromophenyl) sulfenyl)-4-(2-chlorphenyl)-2-butanone: pi-allyl Samaric bromide=1.0:2.5, wherein 4-((2-bromophenyl) sulfenyl)-4-(2-chlorphenyl)-2-butanone 1mmol, Organic solvent is oxolane, and consumption is 30mL, toward the tetrahydrochysene of allylic bromination samarium at-30 DEG C Tetrahydrofuran solution injects the tetrahydrofuran solution of 4-((2-bromophenyl) sulfenyl)-4-(2-chlorphenyl)-2-butanone, React 30 minutes.
The other the same as in Example 1, obtains the 4-bromo-2-of methyl-8-(2-chlorphenyl)-trans-3,4,4 α, 5-tetrahydrochysene-2H- Sulfur chromane-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-furyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(2-furyl)-4-(thiophenyl)-2-butanone: allylic bromination samarium= 1.0:2.5, wherein 4-(2-furyl)-4-(thiophenyl)-2-butanone 1mmol, organic solvent is tetrahydrochysene Furan, consumption is 30mL, injects at-30 DEG C in the tetrahydrofuran solution of allylic bromination samarium The tetrahydrofuran solution of 4-(2-furyl)-4-(thiophenyl)-2-butanone, reacts 30 minutes.
The other the same as in Example 1, obtains 4-methyl-2-(2-furyl)-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur Chromane-4-alcohol, yield 79%.
Embodiment 14:
2,4-dimethyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(III n)
2,4-dimethyl-trans-3,4,4a, the preparation of 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 4-(thiophenyl)-2 pentanone: allylic bromination samarium=1.0:2.5, its Middle 4-(thiophenyl)-2 pentanone 1mmol, organic solvent is oxolane, and consumption is 30mL, in-30 Toward the tetrahydrochysene furan of injection 4-(thiophenyl)-2 pentanone in the tetrahydrofuran solution of allylic bromination samarium at DEG C Mutter solution, react 30 minutes.
The other the same as in Example 1, obtains 2,4-dimethyl-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4- Alcohol, yield 83%
Embodiment 15:
4-ethyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol(IIIo)
The preparation of 4-ethyl-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol
Feed intake the amount of material than for 1-(thiophenyl)-propione: allylic bromination samarium=1.0:2.5, its Middle 1-(thiophenyl)-propione 1mmol, organic solvent is oxolane, and consumption is 30mL, in-30 Toward the tetrahydrochysene furan of injection 1-(thiophenyl)-propione in the tetrahydrofuran solution of allylic bromination samarium at DEG C Mutter solution, react 30 minutes.
The other the same as in Example 1, obtains 4-ethyl-trans-3,4,4 α, 7-tetrahydrochysene-2H-sulfur chromane-4-alcohol, yield 80%.

Claims (9)

1. the method preparing dihydro sulfur chroman derivative, it is characterised in that comprise the following steps:
Under conditions of hexamethyl phosphoramide (HMPA) exists, with allylic bromination samarium as reducing agent, β-arylthio ketone occurs coupling to be cyclized in organic solvent, and reaction terminates, post-treated obtain described Dihydro sulfur chroman derivative；
The structure of described β-arylthio ketone, allylic bromination samarium and dihydro sulfur chroman derivative is the most such as Shown in Formulas I, II and III:
In Formulas I and III, R1Independently selected from C1～C5Alkyl, replacement or unsubstituted phenyl, Replace or unsubstituted furyl；
R2Independently selected from any substituted C1～C5Alkyl, C1～C5Alkoxy or halogen；
R3Independently selected from H or C1～C5Alkyl, R4Independently selected from C1～C5Aliphatic alkyl, Or R4、R3Five-membered ring or hexatomic ring is formed with the group connecting them.
The method preparing dihydro sulfur chroman derivative the most according to claim 1, its feature exists In, described R1For methyl, ethyl, phenyl or 2-furyl.
The method preparing dihydro sulfur chroman derivative the most according to claim 1, its feature exists In, described R2For methyl, methoxyl group, chlorine or bromine.
The method preparing dihydro sulfur chroman derivative the most according to claim 1, its feature exists In, described R3For H or methyl.
The method preparing dihydro sulfur chroman derivative the most according to claim 1, its feature exists In, described R4For methyl, ethyl or propyl group.
The method preparing dihydro sulfur chroman derivative the most according to claim 1, its feature exists In, described organic solvent is oxolane.
The method preparing dihydro sulfur chroman derivative the most according to claim 1, its feature exists In, described β-arylthio ketone is 1.0:2.0～2.5 with the ratio of the amount of the material of allylic bromination samarium.
The method preparing dihydro sulfur chroman derivative the most according to claim 1, its feature exists In, reaction concrete operations are: under nitrogen protection, by samarium powder and allyl bromide, bromoallylene in oxolane Central Plains Position reaction obtains described allylic bromination samarium solution, then hexamethyl phosphoramide is added allyl bromide, bromoallylene Change samarium solution and be cooled to less than-30 DEG C, then the tetrahydrofuran solution addition of β-arylthio ketone is carried out Coupling cyclization.
The method preparing dihydro sulfur chroman derivative the most according to claim 1, its feature exists In, described post processing includes: add saturated aqueous sodium potassium tartrate in reactant liquor, reaction Liquid gradually goes back up to room temperature, is extracted with ethyl acetate, and the organic facies obtained carries out washing, is dried, dense Contracting and column chromatography, obtain described dihydro sulfur chroman derivative.
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