CN107573376A - A kind of preparation method of alkyl sulfide (selenium) for phosphonate ester - Google Patents
A kind of preparation method of alkyl sulfide (selenium) for phosphonate ester Download PDFInfo
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- CN107573376A CN107573376A CN201710800328.5A CN201710800328A CN107573376A CN 107573376 A CN107573376 A CN 107573376A CN 201710800328 A CN201710800328 A CN 201710800328A CN 107573376 A CN107573376 A CN 107573376A
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- selenium
- phosphonate ester
- bfee
- alkyl sulfide
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Abstract
The present invention relates to a kind of alkyl sulfide (selenium) for the preparation method of phosphonate ester, comprise the following steps：1) aryl end alkene, sulphur (selenium) powder, P H reagents and alkali are mixed in toluene solution, then add BFEE, at a temperature of 50~100 DEG C, after reacting 2~12h, be cooled to room temperature, obtain reaction solution；2) reaction solution obtained by step 1) is concentrated with organic solvent, isolated and purified, that is, obtain alkyl sulfide (selenium) for phosphonate ester；The present invention compared with the existing technology, has the characteristics that preparation technology is simply efficient, easy to operate, substrate expansibility is good, yield is high, and gained target product alkyl sulfide (selenium) can be applied to organic synthesis, medical domain for phosphonate ester.
Description
[technical field]
The invention belongs to technical field of organic synthesis, specifically a kind of alkyl sulfide (selenium) is for the preparation side of phosphonate ester
Method.
[background technology]
Thiophosphonate containing P-S-C (sp3) key all has in organic synthesis, pharmaceutical chemistry, functional material etc.
Important application.Such as ecostigmine (Echothiopate), there is special efficacy for treatment glaucoma；Methylpyridine phosphorus
(Azamethiphos), fensulfothion (Fensulfothion) is a kind of efficient insecticide.Selenium is a kind of multi-functional life battalion
Element is supported, it plays an important roll in terms of the diseases such as treatment tumour, cardiovascular disease, diabetes, heart disease.In addition, in organic conjunction
Into, photoelectric material, metallurgy etc. organic selenium compounds, equally with important application.Traditional preparation contains P-S (Se)-C
(sp3) method of key compound is cumbersome, the cycle is longer, is unfavorable for large-scale industrial production application.
[content of the invention]
A kind of alkyl sulfide (selenium) is provided for the preparation side of phosphonate ester present invention aim to solve above-mentioned deficiency
Method, have the characteristics that preparation technology is simply efficient, easy to operate, substrate expansibility is good, yield is high, solve traditional preparation side
It is cumbersome existing for method, the cycle is long, be unfavorable for large-scale production the problem of.
A kind of alkyl sulfide (selenium) is designed to achieve the above object for the preparation method of phosphonate ester, is comprised the following steps：1) will
Aryl end alkene, sulphur (selenium) powder, P-H reagents and alkali are mixed in toluene solution, then add BFEE, 50~
At a temperature of 100 DEG C, after reacting 2~12h, room temperature is cooled to, obtains reaction solution；2) by the reaction solution organic solvent obtained by step 1)
Concentrate, isolate and purify, that is, obtain alkyl sulfide (selenium) for phosphonate ester.
Further, in step 1), aryl end alkene, sulphur powder/selenium powder, P-H reagents, alkali, BFEE rub
Your ratio is (1~2)：(1~2)：1：(1~2)：(1~2).
Further, in step 1), sulphur powder/selenium powder, P-H reagents, aryl end alkene, alkali are weighed in test tube, adds toluene,
Test tube is sealed, then is stirred for reacting by BFEE injecting tube with microsyringe.
Further, in step 1), the P-H reagents are phosphine oxide compound.The phosphine oxide compound is diphenyl phosphine oxide.
Further, in step 1), aryl end alkene is styrene, in tert-butyl group base styrene, p-chlorostyrene
It is any.
Further, in step 1), the alkali is triethylamine.
Further, in step 1), the dosage of the toluene is：Every mM of aryl end vinyl compound 2~6mL first
Benzene.
Further, in step 1), the content of the BFEE is 48~98%.
Further, in step 2), after isolating and purifying, column chromatography for separation is carried out to concentrate, with ethyl acetate and oil
For the mixture of ether as solvent, its volume ratio is ethyl acetate/petroleum ether=1/1~1/10.
The present invention is compared with the existing technology, there is provided a kind of alkyl sulfide (selenium) that efficiently prepares for phosphonate methods, pass through by
Aryl end alkene, sulphur (selenium) powder, P-H reagents and alkali are placed in toluene solution, cold after reaction under BFEE effect
But, reaction solution is obtained, then reaction solution is directly concentrated, isolated and purified, that is, obtain alkyl sulfide (selenium) has for phosphonate ester, this method
The features such as preparation technology is simple efficient, easy to operate, substrate expansibility is good, yield is high, and gained target product alkyl sulfide
(selenium) can be applied to organic synthesis, medical domain for phosphonate ester.
[embodiment]
The invention provides a kind of alkyl sulfide (selenium) for the preparation method of phosphonate ester, comprise the following steps：1) by aryl end
Alkene, sulphur (selenium) powder, P-H reagents and alkali are mixed in toluene solution, BFEE are then added, in 50~100 DEG C of temperature
Under degree, after reacting 2~12h, room temperature is cooled to, obtains reaction solution；2) reaction solution obtained by step 1) is concentrated with organic solvent, divided
From purifying, that is, alkyl sulfide (selenium) is obtained for phosphonate ester.Gained target product alkyl sulfide (selenium) can be applied to organic conjunction for phosphonate ester
Into, medical domain.
In step 1), aryl end alkene, sulphur powder/selenium powder, P-H reagents, alkali, the mol ratio of BFEE are (1~2)：
(1~2)：1：(1~2)：(1~2), by the mol ratio, sulphur powder/selenium powder, P-H reagents, aryl end alkene, alkali are weighed in test tube,
Toluene is added, seals test tube, then be stirred for reacting by BFEE injecting tube with microsyringe.P-H reagents are
Phosphine oxide compound, preferably diphenyl phosphine oxide.Aryl end alkene is styrene, to appointing in tert-butyl group base styrene, p-chlorostyrene
It is a kind of.Alkali is triethylamine, and the dosage of toluene is：Every mM of aryl end vinyl compound 2~6mL toluene, boron trifluoride second
The content of ether is 48~98%.In step 2), after isolating and purifying, column chromatography for separation is carried out to concentrate, with ethyl acetate and stone
For the mixture of oily ether as solvent, its volume ratio is ethyl acetate/petroleum ether=1/1~1/10.
For alkyl sulfide (selenium) of the present invention for the preparation method of phosphonate ester, the reaction expression being related to is as follows：
X:S8Or Se
Wherein, Ar is aryl, R1、R2For aryl.
The present invention is made with reference to specific embodiment further explained below：
Embodiment 1
The preparation method of S- (1- phenylethyls) diphenyl Thiophosphonate, comprises the following steps：Weigh 0.36mmol's
Sulphur powder, 0.3mmol diphenyl phosphine oxides, 0.36mmol styrene, 0.3mmol triethylamines add toluene, sealing examination in test tube
Pipe, then reaction 12h in 0.6mmol BFEE injecting tubes, will be stirred under the conditions of 70 DEG C with microsyringe,
Room temperature is cooled to, obtains reaction solution.Gained reaction solution is concentrated under reduced pressure, right with ethyl acetate/petroleum ether=1/3 (v/v) for solvent
Concentrate carries out column chromatography for separation, obtains 98.4mg target products.
The target product yield of the present embodiment is 97%.Nuclear-magnetism sign is carried out to target product, it is as follows：
1H NMR(500MHz,CDCl3):δ7.85-7.76(m,4H),7.52–7.49(m,1H),7.47-7.44(m,3H),
7.37 (s, 2H), 7.18-7.13 (m, 5H), 4.54-4.48 (m, 1H), 1.73 (d, J=7.1Hz, 3H)13C NMR(125MHz,
CDCl3):δ 142.9 (d, J=4.5Hz), 133.9 (d, J=105.7Hz), 132.6 (d, J=107.9Hz), 132.2,
132.2,131.8 (d, J=10.4Hz), 131.1 (d, J=10.4Hz), 128.5 (d, J=13.0Hz), 128.4,128.4 (d,
), J=13.0Hz 127.3,126.9,44.4 (d, J=2.3Hz), 24.8 (d, J=3.5Hz)；31P NMR(202MHz,
CDCl3):δ40.85..
Embodiment 2
The preparation method of S- (1- (4- (tert-butyl group) phenyl) ethyl) diphenyl Thiophosphonate, comprises the following steps：Claim
Take 0.36mmol sulphur powder, 0.3mmol diphenyl phosphine oxides, 0.36mmol to tert-butyl group base styrene, 0.3mmol triethylamines in examination
Guan Zhong, toluene is added, seal test tube, then with microsyringe by 0.6mmol BFEE injecting tubes, in 70 DEG C of bars
Reaction 12h is stirred under part, room temperature is cooled to, obtains reaction solution.Gained reaction solution is concentrated under reduced pressure, with ethyl acetate/petroleum ether
=1/3 (v/v) is solvent, carries out column chromatography for separation to concentrate, obtains 92mg target products.
The target product yield of the present embodiment is 78%.Nuclear-magnetism sign is carried out to target product, it is as follows：
1H NMR(500MHz,CDCl3):δ7.83-7.75(m,4H),7.51-7.48(m,1H),7.44–7.42(m,3H),
7.36-7.33 (m, 2H), 7.18 (d, J=7.9Hz, 2H), 7.11 (d, J=7.9Hz, 2H), 4.55-4.49m, 1H), 1.73
(d, J=7.0Hz, 3H), 1.26 (s, 9H)13C NMR(125MHz,CDCl3):δ 150.1,139.9 (d, J=4.5Hz),
134.2 (d, J=107.1Hz), 132.8 (d, J=105.1Hz), 132.1,131.8,131.8 (d, J=10.4Hz), 131.1
(d, J=10.4Hz), 128.5 (d, J=12.8Hz), 128.3 (d, J=13.2Hz), 126.6,125.3,44.1 (d, J=
2.0Hz), 34.4,31.3,24.7 (d, J=3.6Hz)31P NMR(202MHz,CDCl3):39.48.
Embodiment 3
The preparation method of S- (1- (4- chlorphenyls) ethyl) diphenyl Thiophosphonate, comprises the following steps：Weigh
0.36mmol sulphur powder, 0.3mmol diphenyl phosphine oxides, 0.36mmol p-chlorostyrenes, 0.3mmol triethylamines add in test tube
Enter toluene, seal test tube, then entered in 0.6mmol BFEE injecting tubes under the conditions of 50 DEG C with microsyringe
Row stirring reaction 12h, is cooled to room temperature, obtains reaction solution.Gained reaction solution is concentrated under reduced pressure, with ethyl acetate/petroleum ether=1/3
(v/v) it is solvent, column chromatography for separation is carried out to concentrate, obtains 74.8mg target products.
The target product yield of the present embodiment is 67%.Nuclear-magnetism sign is carried out to target product, it is as follows：
1H NMR(500MHz,CDCl3):δ 7.80 (dd, J=13.1,7.2Hz, 2H), 7.71 (dd, J=13.1,7.2Hz,
2H),7.52–7.42(m,4H),7.36-7,32(m,2H),7.10–7.06(m,4H),4.56–4.50(m,1H),1.69(d,J
=7.2Hz, 3H)；13C NMR(125MHz,CDCl3):δ 141.4,133.5 (d, J=106.1Hz), 132.9,132.3,132.1
(d, J=110.1Hz), 132.0,131.7 (d, J=10.5Hz), 131.0 (d, J=10.6Hz), 128.6 (d, J=
13.0Hz), 128.4,128.4 (d, J=13.0Hz), 128.4,43.6 (d, J=1.9Hz), 24.5 (d, J=4.6Hz)；31P
NMR(202MHz,CDCl3):41.40.
Embodiment 4
The preparation method of Se- (1- phenylethyls) diphenyl seleno phosphonate ester, comprises the following steps：Weigh 0.36mmol's
Selenium powder, 0.3mmol diphenyl phosphine oxides, 0.36mmol styrene, 0.3mmol triethylamines add toluene, sealing examination in test tube
Pipe, then reaction 12h in 0.6mmol BFEE injecting tubes, will be stirred under the conditions of 50 DEG C with microsyringe,
Room temperature is cooled to, obtains reaction solution.Gained reaction solution is concentrated under reduced pressure, right with ethyl acetate/petroleum ether=1/4 (v/v) for solvent
Concentrate carries out column chromatography for separation, obtains 81.1mg target products.
The target product yield of the present embodiment is 70%.Nuclear-magnetism sign is carried out to target product, it is as follows：
1H NMR(500MHz,CDCl3):δ7.85–7.79(m,4H),7.50–7.37(m,6H),7.21–7.10(m,5H),
4.64 (p, J=7.3Hz, 1H), 1.85 (d, J=7.2Hz, 3H)；13C NMR(125MHz,CDCl3):δ 143.2 (d, J=
3.9Hz), 134.7 (d, J=97.0Hz), 133.7 (d, J=96.1Hz), 132.1 (d, J=2.7Hz), 132.0 (d, J=
3.0Hz), 131.95,131.5 (d, J=10.8Hz), 130.9 (d, J=10.7Hz), 128.5 (d, J=11.1Hz), 128.4
(d, J=11.1Hz), 128.4,127.1,127.0,41.9 (d, J=2.4Hz), 24.4 (d, J=2.7Hz)；31P NMR
(202MHz,CDCl3):38.22。
The present invention is simultaneously not limited to the embodiments described above limitation, other any Spirit Essences and principle without departing from the present invention
Lower made change, modification, replacement, combination, simplification, should be equivalent substitute mode, be included in the protection model of the present invention
Within enclosing.
Claims (10)
1. a kind of alkyl sulfide (selenium) is for the preparation method of phosphonate ester, it is characterised in that comprises the following steps：
1) aryl end alkene, sulphur (selenium) powder, P-H reagents and alkali are mixed in toluene solution, then add BFEE,
At a temperature of 50~100 DEG C, after reacting 2~12h, room temperature is cooled to, obtains reaction solution；
2) reaction solution obtained by step 1) is concentrated with organic solvent, isolated and purified, that is, obtain alkyl sulfide (selenium) for phosphonate ester.
2. the method as described in claim 1, it is characterised in that：In step 1), aryl end alkene, sulphur powder/selenium powder, P-H examinations
Agent, alkali, the mol ratio of BFEE are (1~2)：(1~2)：1：(1~2)：(1~2).
3. method as claimed in claim 2, it is characterised in that：In step 1), sulphur powder/selenium powder, P-H reagents, aryl end are weighed
Alkene, alkali add toluene in test tube, seal test tube, then be stirred in BFEE injecting tube with microsyringe
Reaction.
4. method as claimed in claim 3, it is characterised in that：In step 1), the P-H reagents are phosphine oxide compound.
5. method as claimed in claim 4, it is characterised in that：The phosphine oxide compound is diphenyl phosphine oxide.
6. the method as described in claim 4 or 5, it is characterised in that：In step 1), aryl end alkene is styrene, to uncle
Any of butyl base styrene, p-chlorostyrene.
7. method as claimed in claim 6, it is characterised in that：In step 1), the alkali is triethylamine.
8. method as claimed in claim 7, it is characterised in that：In step 1), the dosage of the toluene is：Every mM of aryl
Hold vinyl compound 2~6mL toluene.
9. method as claimed in claim 8, it is characterised in that：In step 1), the content of the BFEE for 48~
98%.
10. method as claimed in claim 9, it is characterised in that：In step 2), after isolating and purifying, post layer is carried out to concentrate
Analysis separation, using the mixture of ethyl acetate and petroleum ether as solvent, its volume ratio for ethyl acetate/petroleum ether=1/1~
1/10。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108129512A (en) * | 2018-02-07 | 2018-06-08 | 上海应用技术大学 | A kind of allyl sulfide generation or the preparation method of phosphoroselenoate and phosphonate ester |
| CN112940032A (en) * | 2021-01-30 | 2021-06-11 | 上海应用技术大学 | Preparation method of benzyl thiophosphonate |
| CN113264957A (en) * | 2021-05-10 | 2021-08-17 | 新乡医学院 | Preparation method of beta-trifluoromethyl thioester compound |
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| CN108129512A (en) * | 2018-02-07 | 2018-06-08 | 上海应用技术大学 | A kind of allyl sulfide generation or the preparation method of phosphoroselenoate and phosphonate ester |
| CN112940032A (en) * | 2021-01-30 | 2021-06-11 | 上海应用技术大学 | Preparation method of benzyl thiophosphonate |
| CN113264957A (en) * | 2021-05-10 | 2021-08-17 | 新乡医学院 | Preparation method of beta-trifluoromethyl thioester compound |
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