CN104844648B - A kind of synthetic method of group thiophosphate compound - Google Patents
A kind of synthetic method of group thiophosphate compound Download PDFInfo
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- CN104844648B CN104844648B CN201510153369.0A CN201510153369A CN104844648B CN 104844648 B CN104844648 B CN 104844648B CN 201510153369 A CN201510153369 A CN 201510153369A CN 104844648 B CN104844648 B CN 104844648B
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- ester
- thiophenol
- phosphite
- cdcl
- mercaptan
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- -1 thiophosphate compound Chemical class 0.000 title claims abstract description 24
- 238000010189 synthetic method Methods 0.000 title claims abstract description 17
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims abstract description 96
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 150000008301 phosphite esters Chemical class 0.000 claims abstract description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 8
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229950009390 symclosene Drugs 0.000 claims abstract description 6
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 5
- CHJUOCDSZWMLRU-UHFFFAOYSA-N oxo(dipropoxy)phosphanium Chemical compound CCCO[P+](=O)OCCC CHJUOCDSZWMLRU-UHFFFAOYSA-N 0.000 claims description 41
- 239000007788 liquid Substances 0.000 claims description 25
- 150000002148 esters Chemical class 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 8
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical class FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 claims description 6
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical class SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 claims description 6
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical class COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 claims description 6
- UTTUIPRCIQKLQE-UHFFFAOYSA-N C(C)OP(OOC)OOC Chemical compound C(C)OP(OOC)OOC UTTUIPRCIQKLQE-UHFFFAOYSA-N 0.000 claims description 6
- LXXNWCFBZHKFPT-UHFFFAOYSA-N Ethyl 2-mercaptopropionate Chemical compound CCOC(=O)C(C)S LXXNWCFBZHKFPT-UHFFFAOYSA-N 0.000 claims description 6
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 claims description 6
- DVQJZMHWNRXGSM-UHFFFAOYSA-N bis(2-methylpropyl) hydrogen phosphite Chemical compound CC(C)COP(O)OCC(C)C DVQJZMHWNRXGSM-UHFFFAOYSA-N 0.000 claims description 6
- CMKBCTPCXZNQKX-UHFFFAOYSA-N cyclohexanethiol Chemical compound SC1CCCCC1 CMKBCTPCXZNQKX-UHFFFAOYSA-N 0.000 claims description 6
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- BVXOPEOQUQWRHQ-UHFFFAOYSA-N dibutyl phosphite Chemical compound CCCCOP([O-])OCCCC BVXOPEOQUQWRHQ-UHFFFAOYSA-N 0.000 claims description 5
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical class OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 claims description 4
- FTBCOQFMQSTCQQ-UHFFFAOYSA-N 4-bromobenzenethiol Chemical class SC1=CC=C(Br)C=C1 FTBCOQFMQSTCQQ-UHFFFAOYSA-N 0.000 claims description 4
- WVDYBOADDMMFIY-UHFFFAOYSA-N Cyclopentanethiol Chemical compound SC1CCCC1 WVDYBOADDMMFIY-UHFFFAOYSA-N 0.000 claims description 4
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical group COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004494 ethyl ester group Chemical group 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 238000004817 gas chromatography Methods 0.000 claims description 2
- 238000002390 rotary evaporation Methods 0.000 claims description 2
- PMNLUUOXGOOLSP-UHFFFAOYSA-N alpha-mercaptopropionic acid Natural products CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 27
- 230000015572 biosynthetic process Effects 0.000 abstract description 26
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 230000000975 bioactive effect Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 125000003963 dichloro group Chemical group Cl* 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 138
- 239000000463 material Substances 0.000 description 24
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- 238000004679 31P NMR spectroscopy Methods 0.000 description 23
- 238000011017 operating method Methods 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- QVKQJEWZVQFGIY-UHFFFAOYSA-N dipropyl hydrogen phosphate Chemical compound CCCOP(O)(=O)OCCC QVKQJEWZVQFGIY-UHFFFAOYSA-N 0.000 description 6
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical class CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 6
- NFORZJQPTUSMRL-UHFFFAOYSA-N dipropan-2-yl hydrogen phosphite Chemical compound CC(C)OP(O)OC(C)C NFORZJQPTUSMRL-UHFFFAOYSA-N 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- VEMXDEHLAOUMJI-UHFFFAOYSA-N [S].C1(=CC(=CC=C1)C)C Chemical compound [S].C1(=CC(=CC=C1)C)C VEMXDEHLAOUMJI-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- PVQVJLCMPNEFPM-UHFFFAOYSA-N bis(2-methylpropyl) hydrogen phosphate Chemical compound CC(C)COP(O)(=O)OCC(C)C PVQVJLCMPNEFPM-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- XLMPYCGSRHSSSX-UHFFFAOYSA-N 3-Mercapto-2-butanone Chemical compound CC(S)C(C)=O XLMPYCGSRHSSSX-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 241001614291 Anoplistes Species 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- OSVXSBDYLRYLIG-UHFFFAOYSA-N chlorine dioxide Inorganic materials O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- ZMJUYWJINBSMOL-UHFFFAOYSA-N cyclohexyloxy-dihydroxy-sulfanylidene-$l^{5}-phosphane Chemical compound OP(O)(=S)OC1CCCCC1 ZMJUYWJINBSMOL-UHFFFAOYSA-N 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- SAUMVKNLVQDHMJ-UHFFFAOYSA-N dichlorine trioxide Inorganic materials ClOCl(=O)=O SAUMVKNLVQDHMJ-UHFFFAOYSA-N 0.000 description 1
- WZPMZMCZAGFKOC-UHFFFAOYSA-N diisopropyl hydrogen phosphate Chemical compound CC(C)OP(O)(=O)OC(C)C WZPMZMCZAGFKOC-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
Abstract
The present invention relates to a kind of synthetic method of group thiophosphate compound.The present invention, in the dichloro 5 of chlorination reagent 1,3, thiophosphate is synthesized under the promotion of 5 DMHs/sym-closene using phosphite ester and thiophenol or mercaptan.Mild condition, is swift in response, and course of reaction need not add alkali and catalyst, have wide applicability to the substrate of different functional groups.The phosphorothioate backbone that the present invention is efficiently built is the important skeleton of many medicines, agricultural chemicals, bioactive molecule and natural products, and synthetic method of the present invention provides a generally applicable preparation method for the synthesis of this kind of compound.
Description
Technical field
The present invention relates to a kind of synthetic method of group thiophosphate compound.
Background technology
Group thiophosphate compound is the very important compound of a class, and they are in organic synthesis, medicine, bioactivity
The fields such as molecule, agricultural chemicals, material science are widely used.Particularly in medicine and pesticide field, group thiophosphate compound is accounted for
There is consequence, the representative thiophosphate that some of them have been applied, structural formula is as follows：
For the synthetic method of various group thiophosphate compounds, there are reports in current document.
R.Harveyh et al. discloses a kind of method for synthesizing thiophosphate, and this method is hydrogenated by adding highly basic
Sodium, then again with thioether reactant, obtain object.But because sodium hydride alkalescence is very strong, cause functional group compatibility poor, make a lot
Substrate is unsuitable for this method.(R.Harveyh；E.Jacobson；E.Jensen, J.Am.Chem.Soc., 1963,85,
1623-1626.)
Babak Kaboudin et al. disclose a kind of method for synthesizing thiophosphate, and this method is made using cuprous iodide
Intersect the catalyst of dehydrogenation coupling reaction for phosphite ester and thiophenol, and in the presence of organic base, with N, N- dimethyl formyls
Amine is solvent, in room temperature reaction 5 hours, you can obtain phosphorothioate compound with higher yields.However, the reaction time compared with
It is long, and big polar solvent DMF is used, post-reaction treatment is relatively cumbersome.(Babak Kaboudin；
Yaghoub Abedi；Jun-ya Kato；Tsutomu Yokomatsu, Synthesis, 2013,45,2323-2327.)
Yi Chen et al. disclose a kind of method for synthesizing thiophosphate, and this method uses N- chlorosuccinimides
For chlorination reagent, it generates corresponding alkyl or aryl sulphur chloromethylated intermediate with alkyl or aryl thiol reactant, then again should
Intermediate and phosphite reactions, obtain object.Compared to other methods, this method substantially reduces the reaction time, to virtue
Fragrant race's substrate and aliphatic mercaptan substrate are respectively provided with preferable compatibility, but this method needs to carry out two-step reaction, repeatedly adds
Material make it that operation is relatively cumbersome.(Yi Chen；Chin Fa Lee；Green Chem., 2014,16,357-364.)
Jie Bai et al. disclose a kind of method for synthesizing thiophosphate, and this method is with aryl sulfonyl chloride and phosphorous
Acid esters is substrate, and copper acetate is catalyst, under conditions of alkali is not added with, and can obtain 20 kinds of arylthio phosphorus with preferable yield
Acid esters.But the deficiency of this method is that the reaction time is longer, it usually needs reacted 24 hours at a high temperature of 140 DEG C, and
The consumption of phosphite ester is 7 times of aryl sulfonyl chloride, causes the waste of raw material, does not meet the principle of Atom economy.(Jie
Bai；Xiuling Cui；Hui Wang；Yangjie Wu；Chem Commun., 2014,50,8860-8863.)
In summary, existing method still suffers from some shortcoming when synthesizing thiophosphate, and those skilled in the art one
It is straight to study and exploring, it is desirable to be able to find more gentle reaction condition, synthesized within the shorter time, with higher yield
The new method of thiophosphate.
The content of the invention
The technical problem to be solved is：A kind of mild condition, the method for willing synthesis thiophosphate are provided.
The synthetic method reaction equation of group thiophosphate compound of the present invention is as follows：
Wherein, R1For alkyl, R2For aryl or alkyl；
Phosphite ester is dimethylphosphite, diethyl phosphite, di-n-propyl phosphite, diisopropyl phosphite, Asia
Dibutylphosphoric acid ester, phosphorous acid diisobutyl ester, phosphorous acid dimethoxy ethyl ester or phosphorous acid dichloride ethyl ester；
Thiophenol is 2,4- thiophenol dimethyl benzenes, 2- methylbenzene phenyl-sulfhydrates, 3- methylbenzene phenyl-sulfhydrates, 4- methoxybenzenethiols, 2- naphthalenes
Thiophenol, 4- chlorothio-phenols, 4- bromo thiophenols or 4- fluoro thiophenols；
Mercaptan is the butanone of 3- sulfydryls -2, benzyl mercaptan, cyclohexanethiol, cyclopentyl mercaptan, 3- mercapto-propionates, 2- mercaptos
Acetic acid methyl ester or ethyl 2-mercaptopropionate；
Chlorination reagent is chloro- 5, the 5- DMHs of 1,3- bis- or sym-closene；Solvent is dichloromethane or 1,2-
Dichloroethanes；
The reactions steps of the synthetic method are as follows：Phosphite ester, thiophenol or mercaptan are added to the molten of chloride containing reagent
In agent, it is stirred at room temperature 5~10 minutes, is reacted with " one kettle way "；Reaction process is monitored with gas-chromatography, question response is complete
Quan Hou, filtering reacting liquid boils off filtrate rotary evaporation after solvent, then carries out pillar layer separation, obtains required D2EHDTPA
Ester type compound；
The phosphite ester, thiophenol or mercaptan, the mol ratio of chloro- 5, the 5- DMHs of 1,3- bis- are 1~1.2: 1:
0.5；
The mol ratio of chloro- 5, the 5- DMHs of the phosphite ester, thiophenol, 1,3- bis- is 1~1.2: 1: 0.5；
The phosphite ester, thiophenol or mercaptan, the mol ratio of sym-closene are 1: 1: 0.35.
Beneficial effects of the present invention：The synthetic method is to use chloro- 5, the 5- DMHs of 1,3- bis- or trichlorine isocyanide to urinate
Acid occurs dehydrogenation coupling reaction between phosphite ester and thiophenol/mercaptan and obtains thiophosphate, compare as chlorination reagent
In synthetic method of the prior art, the advantage of synthetic method of the invention is as follows：
(1) in method of the invention, reaction condition is gentleer, exists without highly basic, big polar solvent (such as DMF) and only
It can complete at room temperature.
(2) reagent used in method of the invention is cheap and easy to get, and course of reaction is without inert gas shielding, using " one
Pot method " operation is easier.
(3) synthetic method of the invention is quicker, needs a few hours and dozens of hour mostly relative to prior art
Reaction time, the present invention, which only needs to several minutes, can react complete.
(4) because the present invention is without using highly basic, therefore the synthetic method of the present invention has universality, can be used for various Asias
Phosphate and thiophenol/mercaptan.According to the structure of target product, the mercaptan or sulphur of any phosphite ester and different structure can be selected
Phenol, hence in so that group thiophosphate compound is no longer limited by the reaction condition of harshness.
(5) method of the invention can obtain satisfied yield, obtain D2EHDTPA ester products.
The phosphorothioate backbone that the present invention is efficiently built is many medicines, agricultural chemicals, bioactive molecule and natural products
Important skeleton, synthetic method of the present invention provides a generally applicable preparation side for the synthesis of this kind of compound
Method.
Embodiment
Embodiment 1
With 2,4- thiophenol dimethyl benzenes (2a) and di-n-propyl phosphite (1a) for Material synthesis 2,4- 3,5-dimethylphenyl sulphur
For phosphoric acid di-n-propyl ester (3a)：
Added in equipped with magneton 10mL reaction bulbs chloro- 5, the 5- DMHs (0.0493g, 0.25mmol) of 1,3- bis-,
Dichloromethane (1.5mL), be stirred at room temperature it is uniform, be stirred vigorously down add thereto di-n-propyl phosphite (1a, 0.083g,
0.5mmol) with 2,4- thiophenol dimethyl benzenes (2a, 0.069g, 0.5mmol), close the lid, room temperature is stirred vigorously 10 minutes；Gas
The reaction of phase chromatogram monitoring is complete；Reacting liquid filtering, colourless transparent liquid (3a) 0.139g is obtained after being spin-dried for through column chromatography for separation, production
Rate 92%.
Rf=0.33 (VN-hexane/VEthyl acetate=4/1)；1H NMR (300MHz, CDCl3）δ 7.47 (dd, J=7.9,2.3Hz,
1H), 7.07 (s, 1H), 6.98 (d, J=7.9Hz, 1H), 4.12-3.94 (m, 4H), 2.48 (s, 3H), 2.30 (d, J=
2.1Hz, 3H), 1.66 (dt, J=13.7,6.9Hz, 4H), 0.92 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3)δ
142.20 (d, J=5.4Hz), 139.72 (d, J=3.3Hz), 136.36 (d, J=4.2Hz), 131.84 (d, J=2.8Hz),
127.70 (d, J=2.8Hz), 122.24 (d, J=7.4Hz), 69.61 (d, J=7.1Hz), 23.74 (d, J=7.2Hz),
21.35 (d, J=17.7Hz), 10.14 (s)；31P NMR (121MHz, CDCl3)δ23.54(s)；MS (70eV, EI) C14H23O3PS
[M]：302.09.
Embodiment 2
With 2,4- thiophenol dimethyl benzenes (2a) and di-n-propyl phosphite (1a) for Material synthesis 2,4- 3,5-dimethylphenyl sulphur
For phosphoric acid di-n-propyl ester (3a)：
Operating method be the same as Example 1.Difference is, is replaced using sym-closene (0.04g, 0.175mmol)
1,3- bis- chloro- 5,5- DMHs are used as chlorination reagent.Obtain colourless transparent liquid (3a) 0.133g, yield 88%.
Rf=0.33 (VN-hexane/VEthyl acetate=4/1)；1H NMR (300MHz, CDCl3) δ 7.47 (dd, J=7.9,2.3Hz,
1H), 7.07 (s, 1H), 6.98 (d, J=7.9Hz, 1H), 4.12-3.94 (m, 4H), 2.48 (s, 3H), 2.30 (d, J=
2.1Hz, 3H), 1.66 (dt, J=13.7,6.9Hz, 4H), 0.92 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3)δ
142.20 (d, J=5.4Hz), 139.72 (d, J=3.3Hz), 136.36 (d, J=4.2Hz), 131.84 (d, J=2.8Hz),
127.70 (d, J=2.8Hz), 122.24 (d, J=7.4Hz), 69.61 (d, J=7.1Hz), 23.74 (d, J=7.2Hz),
21.35 (d, J=17.7Hz), 10.14 (s)；31P NMR (121MHz, CDCl3)δ23.54(s)；MS (70eV, EI) C14H23O3PS
[M]：302.09.
Embodiment 3
With 2- methylbenzene phenyl-sulfhydrates (2b) and di-n-propyl phosphite (1a) for Material synthesis 2- aminomethyl phenyls D2EHDTPA two
N-propyl (3b)：
Operating method be the same as Example 1.Difference is, 2,4- dimethyl benzene sulphur is replaced using 2- methylbenzene phenyl-sulfhydrates (2b)
Phenol (2a).Obtain colourless transparent liquid (3b) 0.127g, yield 88%.
Rf=0.34 (VN-hexane/VEthyl acetate=4/1)；1H NMR (300MHz, CDCl3) δ 7.66-7.60 (m, 1H), 7.28 (d,
J=2.3Hz, 2H), 7.22-7.14 (m, 1H), 4.14-3.96 (m, 4H), 2.54 (d, J=1.3Hz, 3H), 1.68 (dd, J=
14.0,7.3Hz, 4H), 0.92 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3) δ 142.32 (d, J=5.7Hz),
136.28 (d, J=4.2Hz), 130.96 (d, J=2.6Hz), 129.50 (d, J=3.0Hz), 126.85 (d, J=2.7Hz),
125.99 (d, J=7.4Hz), 69.69 (d, J=7.1Hz), 23.72 (d, J=7.2Hz), 21.56 (s), 10.12 (s)；31P
NMR (121MHz, CDCl3)δ23.09(s)；MS (70eV, EI) C13H21O3PS[M]：288.02.
Embodiment 4
With 3- methylbenzene phenyl-sulfhydrates (2c) and di-n-propyl phosphite (1a) for Material synthesis 3- aminomethyl phenyls D2EHDTPA two
N-propyl (3c)：
Operating method be the same as Example 1.Difference is, 2,4- dimethyl benzene sulphur is replaced using 3- methylbenzene phenyl-sulfhydrates (2c)
Phenol (2a).Obtain colourless transparent liquid (3c) 0.129g, yield 90%.
Rf=0.225 (VN-hexane/VEthyl acetate=4/1)；1H NMR (300MHz, CDCl3) δ 7.36 (dd, J=5.5,5.0Hz,
2H), 7.22 (t, J=7.5Hz, 1H), 7.15 (dd, J=7.6,0.6Hz, 1H), 4.28-3.85 (m, 4H), 2.33 (s, 3H),
1.79-1.50 (m, 4H), 0.91 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3) δ 139.30 (d, J=2.3Hz),
135.27 (d, J=5.3Hz), 131.66 (d, J=5.3Hz), 129.90 (d, J=2.8Hz), 129.21 (d, J=2.2Hz),
126.31 (d, J=7.1Hz), 69.60 (d, J=6.7Hz), 23.65 (d, J=7.3Hz), 21.36 (s), 10.13 (s)；31P
NMR (121MHz, CDCl3)δ23.17(s)；MS (70eV, EI) C13H21O3PS[M]：288.07.
Embodiment 5
With 4- methoxybenzenethiols (2d) and di-n-propyl phosphite (1a) for Material synthesis 4- methoxyphenylthio phosphorus
Sour di-n-propyl ester (3d)：
Operating method be the same as Example 1.Difference is, 2,4- dimethyl benzenes are replaced using 4- methoxybenzenethiols (2d)
Thiophenol (2a).Obtain colourless transparent liquid (3d) 0.141g, yield 93%.
Rf=0.05 (VPetroleum ether/VEthyl acetate=9/1)；1H NMR (300MHz, CDCl3) δ 7.50-7.44 (m, 2H), 6.90-
6.84 (m, 2H), 4.14-3.97 (m, 4H), 3.80 (s, 3H), 1.74-1.61 (m, 4H), 0.92 (t, J=7.4Hz, 6H)；13C
NMR (75MHz, CDCl3) δ 160.61 (d, J=2.8Hz), 136.49 (d, J=4.8Hz), 116.84 (d, J=7.5Hz),
115.08 (d, J=2.5Hz), 69.56 (d, J=6.7Hz), 55.51 (s), 23.71 (d, J=7.2Hz), 10.16 (s)；31P
NMR (121MHz, CDCl3)δ23.59(s)；MS (70eV, EI) C13H21O4PS[M]：304.10.
Embodiment 6
With 2- thionaphthols (2e) and di-n-propyl phosphite (1a) for Material synthesis 2- naphthalene D2EHDTPA di-n-propyl esters (3e)：
Operating method be the same as Example 1.Difference is, 2,4- thiophenol dimethyl benzenes are replaced using 2- thionaphthols (2e)
(2a).Solvent uses 1,2- dichloroethanes to replace dichloromethane.White solid (3e) 0.137g, yield are obtained after column chromatography for separation
85%.
Rf=0.1 (VPetroleum ether/VEthyl acetate=9/1)；1H NMR (300MHz, CDCl3) δ 8.09 (t, J=2.2Hz, 1H),
7.87-7.75 (m, 3H), 7.65-7.58 (m, 1H), 7.55-7.47 (m, 2H), 4.28-3.94 (m, 4H), 1.82-1.53 (m,
4H), 0.91 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3) δ 134.47 (d, J=6.8Hz), 133.75 (d, J=
2.3Hz), 133.16 (d, J=1.8Hz), 131.08 (d, J=4.2Hz), 129.08 (d, J=1.6Hz), 127.85 (dd, J=
3.6,1.1Hz), 127.16 (d, J=1.0Hz), 126.87 (d, J=0.7Hz), 124.00 (d, J=7.3Hz), 69.74 (d, J
=6.8Hz), 23.69 (d, J=7.2Hz), 10.15 (s)；31P NMR (121MHz, CDCl3)δ22.91(s)；MS (70eV, EI)
C16H21O3PS[M]：324.10.
Embodiment 7
With 4- chlorothio-phenols (2f) and di-n-propyl phosphite (1a) for Material synthesis 4- chlorophenylthio di(2-ethylhexyl)phosphates positive third
Ester (3f)：
Operating method be the same as Example 1.Difference is, 2,4- thiophenol dimethyl benzenes are replaced using 4- chlorothio-phenols (2f)
(2a).Obtain colourless transparent liquid (3f) 0.137g, yield 89%.
Rf=0.162 (VPetroleum ether/VEthyl acetate=9/1)；1H NMR (300MHz, CDCl3) δ 7.54-7.47 (m, 2H), 7.35-
7.29 (m, 2H), 4.07 (qdt, J=9.9,8.2,6.6Hz, 4H), 1.74-1.61 (m, 4H), 0.92 (t, J=7.4Hz, 6H)
；13C NMR (75MHz, CDCl3) δ 135.87 (d, J=5.3Hz), 135.58 (d, J=3.4Hz), 129.66 (d, J=
2.2Hz), 69.84 (d, J=6.8Hz), 23.68 (d, J=7.2Hz), 10.14 (s)；31P NMR (121MHz, CDCl3)δ
22.31(s)；MS (70eV, EI) C12H18ClO2PS[M]：307.93.
Embodiment 8
With 4- bromo thiophenols (2g) and di-n-propyl phosphite (1a) for Material synthesis 4- bromophenyls D2EHDTPA two positive third
Ester (3g)：
Operating method be the same as Example 1.Difference is, 2,4- thiophenol dimethyl benzenes are replaced using 4- bromo thiophenols (2g)
(2a).Obtain colourless transparent liquid (3g) 0.16g, yield 91%.
Rf=0.135 (VPetroleum ether/VEthyl acetate=9/1)；1H NMR (300MHz, CDCl3) δ 7.52-7.39 (m, 4H), 4.17-
3.97 (m, 4H), 1.75-1.62 (m, 4H), 0.92 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3) δ 136.09 (d, J
=5.3Hz), 132.62 (d, J=2.2Hz), 126.07 (d, J=7.3Hz), 123.73 (d, J=3.5Hz), 69.86 (d, J=
6.8Hz), 23.69 (d, J=7.2Hz), 10.14 (s)；31P NMR (121MHz, CDCl3)δ22.04(s)；MS (70eV, EI)
C12H18BrO3PS[M]：353.91.
Embodiment 9
With 4- fluoro thiophenols (2h) and di-n-propyl phosphite (1a) for Material synthesis 4- fluorophenylthio di(2-ethylhexyl)phosphates positive third
Ester (3h)：
Operating method be the same as Example 1.Difference is, 2,4- thiophenol dimethyl benzenes are replaced using 4- fluoro thiophenols (2h)
(2a).Obtain colourless transparent liquid (3h) 0.119g, yield 82%.
Rf=0.135 (VPetroleum ether/VEthyl acetate=9/1)；1H NMR (300MHz, CDCl3) δ 7.64-7.45 (m, 2H), 7.09-
7.00 (m, 2H), 4.07 (qdt, J=9.9,8.2,6.6Hz, 4H), 1.75-1.58 (m, 4H), 0.92 (t, J=7.4Hz, 6H)
；13C NMR (75MHz, CDCl3) δ 136.80 (dd, J=8.4,5.1Hz), 116.81 (d, J=2.3Hz), 116.52 (d, J=
2.3Hz), 69.77 (d, J=6.8Hz), 23.70 (d, J=7.2Hz), 10.14 (s)；31P NMR (121MHz, CDCl3)δ
22.74(s)；MS (70eV, EI) C12H18FO3PS[M]：291.98.
Embodiment 10
With 2,4- thiophenol dimethyl benzenes (2a) and diisopropyl phosphite (1b) for Material synthesis 2,4- 3,5-dimethylphenyl sulphur
For diisopropyl phosphate (3i)：
Operating method be the same as Example 1.Difference is, phosphorous acid two positive third is replaced using diisopropyl phosphite (1b)
Ester (1a).Obtain colourless transparent liquid (3i) 0.136g, yield 90%.
1H NMR (300MHz, CDCl3) δ 7.52 (dd, J=7.9,2.3Hz, 1H), 7.06 (s, 1H), 7.00-6.94 (m,
1H), 4.72 (dhept, J=8.7,6.2Hz, 2H), 2.47 (d, J=0.8Hz, 3H), 2.29 (d, J=2.0Hz, 3H), 1.31
(d, J=6.2Hz, 6H), 1.24 (d, J=6.2Hz, 6H)；13C NMR (75MHz, CDCl3) δ 141.98 (d, J=5.6Hz),
139.40 (d, J=3.3Hz), 136.03 (d, J=4.2Hz), 131.73 (d, J=2.7Hz), 127.57 (d, J=2.7Hz),
122.87 (d, J=7.3Hz), 73.27 (d, J=7.2Hz), 24.02 (d, J=4.2Hz), 23.67 (d, J=5.6Hz),
21.35 (dd, J=20.3,0.7Hz)；31PNMR (121MHz, CDCl3)δ21.44(s)；MS (70eV, EI) C14H23O3PS[M]：
301.96.
Embodiment 11
With 2,4- thiophenol dimethyl benzenes (2a) and dibutyl phosphite (1c) for Material synthesis 2,4- 3,5-dimethylphenyls are thio
Dibutylphosphoric acid ester (3j)：
Operating method be the same as Example 1.Difference is, di-n-propyl phosphite is replaced using dibutyl phosphite (1c)
(1a).Obtain colourless transparent liquid (3j) 0.153g, yield 93%.
1H NMR (300MHz, CDCl3) δ 7.47 (dd, J=7.9,2.2Hz, 1H), 7.07 (s, 1H), 6.97 (d, J=
7.9Hz, 1H), 4.16-3.98 (m, 4H), 2.48 (s, 3H), 2.30 (d, J=2.0Hz, 3H), 1.61 (dt, J=14.7,
6.6Hz, 4H), 1.35 (dq, J=14.5,7.3Hz, 4H), 0.90 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3)δ
142.17 (d, J=5.4Hz), 139.70 (d, J=3.3Hz), 136.31 (d, J=4.2Hz), 131.82 (d, J=2.7Hz),
127.68 (d, J=2.8Hz), 122.24 (d, J=7.4Hz), 77.58 (s), 77.16 (s), 76.74 (s), 67.86 (d, J=
7.1Hz), 32.34 (d, J=7.0Hz), 21.34 (dd, J=18.5,0.8Hz), 18.79 (s), 13.70 (s)；31P NMR
(121MHz, CDCl3)δ23.56(s)；MS (70eV, EI) C16H27O3PS[M]：329.95.
Embodiment 12
With 2,4- thiophenol dimethyl benzenes (2a) and phosphorous acid dimethoxy ethyl ester (1d) for Material synthesis 2,4- dimethyl benzenes
Base D2EHDTPA dimethoxy ethyl ester (3k)：
Operating method be the same as Example 1.Difference is, phosphorous acid two is replaced using phosphorous acid dimethoxy ethyl ester (1d)
N-propyl (1a).Obtain colourless transparent liquid (3k) 0.139g, yield 83%.
1H NMR (300MHz, CDCl3) δ 7.52 (dd, J=7.9,2.4Hz, 1H), 7.07 (s, 1H), 6.98 (d, J=
7.9Hz, 1H), 4.28-4.12 (m, 4H), 3.58-3.51 (m, 4H), 3.35 (s, 6H), 2.48 (d, J=0.9Hz, 3H), 2.30
(d, J=2.2Hz, 3H)；13C NMR (75MHz, CDCl3) δ 142.43 (d, J=5.5Hz), 139.91 (d, J=3.5Hz),
136.62 (d, J=4.3Hz), 131.87 (d, J=2.9Hz), 127.76 (d, J=2.9Hz), 121.63 (d, J=7.5Hz),
71.31 (d, J=7.3Hz), 66.81(d, J=7.0Hz), 59.08 (s), 21.35 (d, J=17.6Hz)；31P NMR
(121MHz, CDCl3)δ24.72(s)；MS (70eV, EI) C14H23O5PS[M]：334.94.
Embodiment 13
With 2,4- thiophenol dimethyl benzenes (2a) and phosphorous acid dichloride ethyl ester (1e) for Material synthesis 2,4- 3,5-dimethylphenyl sulphur
For di(2-ethylhexyl)phosphate chloroethene ester (3l)：
Operating method be the same as Example 1.Difference is, phosphorous acid two positive third is replaced using phosphorous acid dichloride ethyl ester (1e)
Ester (1a).Obtain colourless transparent liquid (3l) 0.051g, yield 30%.
1H NMR (300MHz, CDCl3) δ 7.50 (dd, J=7.9,2.5Hz, 1H), 7.10 (s, 1H), 7.01 (d, J=
7.9Hz, 1H), 4.38-4.20 (m, 4H), 3.64 (t, J=5.9Hz, 4H), 2.49 (d, J=1.2Hz, 3H), 2.32 (d, J=
2.4Hz, 3H)；13C NMR (75MHz, CDCl3) δ 142.61 (d, J=5.5Hz), 140.47 (d, J=3.6Hz), 136.72 (d,
J=4.3Hz), 132.12 (d, J=3.1Hz), 127.95 (d, J=3.0Hz), 120.78 (d, J=7.8Hz), 77.58 (s),
77.16 (s), 76.74 (s), 67.30 (d, J=6.7Hz), 42.33 (d, J=7.5Hz), 21.40 (d, J=17.7Hz)；31P
NMR (121MHz, CDCl3)δ24.87(s)；MS (70eV, EI) C12H17Cl2O3PS[M]：341.94.
Embodiment 14
With the butanone of 3- sulfydryls -2 (2i) and di-n-propyl phosphite (1a) for Material synthesis 3- methyl -2- carbonyls-thio phosphorus
Sour di-n-propyl ester (3m)：
Operating method be the same as Example 1.Difference is, 2,4- dimethyl benzenes are replaced using 3- sulfydryl -2- butanone (2i)
Thiophenol (2a), and the consumption of di-n-propyl phosphite is changed to 0.6mmol, reacts at room temperature 5 minutes.Obtain colourless transparent liquid (3m)
0.069g, yield 52%.
1H NMR (300MHz, CDCl3) δ 4.14-3.96 (m, 5H), 2.33 (s, 3H), 1.80-1.66 (m, 4H), 1.52
(dd, J=7.2,0.5Hz, 3H), 0.97 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3) δ 205.20 (d, J=
5.2Hz), 69.63 (dd, J=6.8,3.3Hz), 49.20 (d, J=3.3Hz), 27.35 (s), 23.65 (dd, J=7.5,
0.6Hz), 18.69 (d, J=6.4Hz), 10.18 (s)；31P NMR (121MHz, CDCl3)δ25.44(s)；MS (70eV, EI)
C10H21O4PS[M]：268.31.
Embodiment 15
With 2,4- thiophenol dimethyl benzenes (2a) and diethyl phosphite (1f) for Material synthesis 2,4- 3,5-dimethylphenyls are thio
Diethyl phosphate (3n)：
Operating method be the same as Example 1.Difference is, di-n-propyl phosphite is replaced using diethyl phosphite (1f)
(1a), obtains colourless transparent liquid (3n) 0.122g, yield 89%.
1H NMR (300MHz, CDCl3) δ 7.47 (dd, J=7.9,2.3Hz, 1H), 7.08 (s, 1H), 6.99 (d, J=
7.9Hz, 1H), 4.24-4.08 (m, 4H), 2.48 (s, 3H), 2.30 (d, J=2.1Hz, 3H), 1.30 (td, J=7.1,
0.8Hz, 6H)；13CNMR (75MHz, CDCl3) δ 142.16 (d, J=5.4Hz), 139.72 (d, J=3.4Hz), 136.32 (d, J
=4.2Hz), 131.80 (d, J=2.8Hz), 127.68 (d, J=2.8Hz), 122.13 (d, J=7.4Hz), 64.10 (d, J=
6.7Hz), 21.28 (d, J=14.6Hz), 16.14 (d, J=7.1Hz)；31P NMR (121MHz, CDCl3)δ23.46(s)；MS
(70eV, EI) C12H19O3PS[M]：274.32.
Embodiment 16
With 2,4- thiophenol dimethyl benzenes (2a) and dimethylphosphite (1g) for Material synthesis 2,4- 3,5-dimethylphenyls are thio
Dimethyl phosphate (3o)：
Operating method be the same as Example 1.Difference is, di-n-propyl phosphite is replaced using dimethylphosphite (1g)
(1a), obtains colourless transparent liquid (3o) 0.108g, yield 88%.
1H NMR (300MHz, CDCl3) δ 7.45 (dd, J=7.9,2.3Hz, 1H), 7.08 (s, 1H), 7.01-6.96 (m,
1H), 3.81 (s, 3H), 3.77 (s, 3H), 2.49 (d, J=0.9Hz, 3H), 2.31 (d, J=2.2Hz, 3H)；13C NMR
(75MHz, CDCl3) δ 142.16 (d, J=5.4Hz), 139.89 (d, J=3.5Hz), 136.30 (d, J=4.2Hz), 13186
(d, J=2.8Hz), 127.75 (d, J=2.9Hz), 121.50 (d, J=7.4Hz), 54.30 (d, J=6.6Hz), 21.20 (d,
J=13.8Hz)；31P NMR (121MHz, CDCl3)δ26.54(s)；MS (70eV, EI) C10H15O3PS[M]：245.91.
Embodiment 17
With 2,4- thiophenol dimethyl benzenes (2a) and phosphorous acid diisobutyl ester (1h) for Material synthesis 2,4- 3,5-dimethylphenyl sulphur
For phosphoric acid diisobutyl ester (3p)：
Operating method be the same as Example 1.Difference is, phosphorous acid two positive third is replaced using phosphorous acid diisobutyl ester (1h)
Ester (1a), obtains colourless transparent liquid (3p) 0.153g, yield 93%.
1H NMR (300MHz, CDCl3) δ 7.47 (dd, J=7.9,2.3Hz, 1H), 7.06 (s, 1H), 6.99-6.93 (m,
1H), 3.92-3.75 (m, 4H), 2.48 (s, 3H), 2.29 (d, J=2.1Hz, 3H), 1.91 (dp, J=13.3,6.7Hz, 2H),
0.90 (d, J=6.7Hz, 12H)；13C NMR (75MHz, CDCl3) δ 142.17 (d, J=5.4Hz), 139.68 (d, J=
3.4Hz), 136.37 (d, J=4.2Hz), 131.80 (d, J=2.8Hz), 127.65 (d, J=2.8Hz), 122.19 (d, J=
7.4Hz), 73.91 (d, J=7.6Hz), 29.17 (d, J=7.3Hz), 21.50 (s), 21.21 (s), 18.79 (s)；31P NMR
(121MHz, CDCl3)δ23.38(s)；MS (70eV, EI) C16H27O3PS[M]：329.94.
Embodiment 18
It is Material synthesis dibenzylsulfide for phosphoric acid di-n-propyl ester (3q) with benzyl mercaptan (2j) and di-n-propyl phosphite (1a)：
Operating method be the same as Example 1.Difference is, 2,4- thiophenol dimethyl benzenes are replaced using benzyl mercaptan (2j)
(2a), obtains colourless transparent liquid (3q) 0.122g, yield 85%.
1H NMR (300MHz, CDCl3) δ 7.39-7.26 (m, 5H), 4.07-3.87 (m, 6H), 1.72-1.59 (m, 4H),
0.93 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3) δ 137.69 (d, J=5.6Hz), 129.05 (s), 128.79
(s), 127.74 (s), 69.12 (d, J=6.2Hz), 35.07 (d, J=3.8Hz), 23.61 (d, J=7.5Hz), 10.17 (s)
；31P NMR (121MHz, CDCl3)δ26.86(s)；MS (70eV, EI) m/z (EI) C13H21O3PS[M]：287.91.
Embodiment 19
With cyclohexanethiol (2k) and di-n-propyl phosphite (1a) for Material synthesis cyclohexyl thio phosphoric acid di-n-propyl ester
(3r)：
Operating method be the same as Example 1.Difference is, 2,4- thiophenol dimethyl benzenes are replaced using cyclohexanethiol (2k)
(2a), obtains colourless transparent liquid (3r) 0.112g, yield 80%.
1H NMR (300MHz, CDCl3) δ 4.12-3.94 (m, 4H), 3.35-3.21 (m, 1H), 1.81-1.66 (m, 6H),
1.61-1.22 (m, 8H), 0.97 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3) δ 69.03 (d, J=6.6Hz),
45.71 (d, J=3.5Hz), 35.48 (d, J=6.0Hz), 26.09 (s), 25.44 (s), 23.70 (d, J=7.4Hz), 10.24
(s)；31P NMR (121MHz, CDCl3)δ27.78(s)；MS (70eV, EI) m/z (EI) C12H25O3PS[M]：281.02.
Embodiment 20
With cyclopentyl mercaptan (2l) and di-n-propyl phosphite (1a) for Material synthesis cyclopenta D2EHDTPA di-n-propyl ester
(3s)：
Operating method be the same as Example 1.Difference is, 2,4- thiophenol dimethyl benzenes are replaced using cyclopentyl mercaptan (2l)
(2a), obtains colourless transparent liquid (3s) 0.110g, yield 83%.
1H NMR (300MHz, CDCl3) δ 4.13-3.96 (m, 4H), 3.56-3.42 (m, 1H), 2.19-2.05 (m, 2H),
1.79-1.68 (m, 6H), 1.68-1.57 (m, 4H), 0.97 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3)δ69.01
(d, J=6.5Hz), 44.82 (d, J=3.7Hz), 35.50 (d, J=6.8Hz), 24.47 (s), 23.72 (d, J=7.4Hz),
10.23(s)；31P NMR (121MHz, CDCl3)δ27.63(s)；MS (70eV, EI) m/z (EI) C11H23O3PS[M]：267.05.
Embodiment 21
With 3- mercapto-propionates (2m) and di-n-propyl phosphite (1a) for the thio phosphorus of Material synthesis methyl propionate base -3-
Sour di-n-propyl ester (3t)：
Operating method be the same as Example 1.Difference is, 2,4- dimethyl benzenes are replaced using 3- mercapto-propionates (2m)
Thiophenol (2a), obtains colourless transparent liquid (3t) 0.131g, yield 92%.
1H NMR (300MHz, CDCl3) δ 4.14-3.94 (m, 4H), 3.70 (s, 3H), 3.07 (dt, J=16.5,7.1Hz,
2H), 2.76 (t, J=7.1Hz, 2H), 1.80-1.65 (m, 4H), 0.97 (t, J=7.4Hz, 6H)；13C NMR (75MHz,
CDCl3) δ 171.80 (s), 69.30 (d, J=6.5Hz), 52.03 (s), 35.62 (d, J=3.9Hz), 25.73 (d, J=
4.1Hz), 23.68 (d, J=7.4Hz), 10.18 (s)；31P NMR (121MHz, CDCl3)δ27.27(s)；MS (70eV, EI) m/
z(EI)C10H21O5PS[M]：285.12.
Embodiment 22
With 2- methyl thioglycolates (2n) and di-n-propyl phosphite (1a) for the thio phosphorus of Material synthesis methyl acetate base -2-
Sour di-n-propyl ester (3u)：
Operating method be the same as Example 1.Difference is, 2,4- dimethyl benzenes are replaced using 2- methyl thioglycolates (2n)
Thiophenol (2a), obtains colourless transparent liquid (3u) 0.129g, yield 95%.
1H NMR (300MHz, CDCl3) δ 4.17-4.00 (m, 4H), 3.76 (s, 3H), 3.61 (d, J=15.2Hz, 2H),
1.80-1.67 (m, 4H), 0.97 (t, J=7.4Hz, 6H)；13C NMR (75MHz, CDCl3) δ 169.40 (d, J=5.1Hz),
69.56 (d, J=6.3Hz), 53.00 (s), 32.30 (d, J=3.8Hz), 23.64 (d, J=7.4Hz), 10.15 (s)；31P
NMR (121MHz, CDCl3)δ25.46(s)；MS (70eV, EI) m/z (EI) C9H19O5PS[M]：271.00.
Embodiment 23
With ethyl 2-mercaptopropionate (2o) and di-n-propyl phosphite (1a) for the thio phosphorus of Material synthesis ethyl propionate base -2-
Sour di-n-propyl ester (3v)：
Operating method be the same as Example 1.Difference is, 2,4- dimethyl benzenes are replaced using ethyl 2-mercaptopropionate (2o)
Thiophenol (2a), obtains colourless transparent liquid (3v) 0.130g, yield 87%.
1H NMR (300MHz, CDCl3) δ 4.20 (q, J=7.1Hz, 2H), 4.14-3.98 (m, 4H), 3.94 (dd, J=
13.3,7.2Hz, 1H), 1.79-1.66 (m, 4H), 1.60 (d, J=7.2Hz, 3H), 1.29 (t, J=7.1Hz, 3H), 0.97
(td, J=7.4,1.2Hz, 6H)；13C NMR (75MHz, CDCl3) δ 172.10 (d, J=5.9Hz), 69.45（Dd, J=6.4,
4.6Hz), 61.90 (s), 42.72 (d, J=3.4Hz), 23.64 (dd, J=7.4,1.5Hz), 20.20 (d, J=6.0Hz),
14.19 (s), 10.16 (d, J=0.8Hz)；31P NMR (121MHz, CDCl3)δ25.14(s)；MS (70eV, EI) m/z (EI)
C11H23O5PS[M]：298.99.
Claims (1)
1. a kind of synthetic method of group thiophosphate compound, it is characterized in that the reaction equation of the synthetic method is as follows：
Phosphite ester is dimethylphosphite, diethyl phosphite, di-n-propyl phosphite, phosphorous acid two wherein shown in formula (1)
Isopropyl ester, dibutyl phosphite, phosphorous acid diisobutyl ester, phosphorous acid dimethoxy ethyl ester or phosphorous acid dichloride ethyl ester；Formula (2) institute
The compound shown be thiophenol or mercaptan, wherein thiophenol be 2,4- thiophenol dimethyl benzenes, 2- methylbenzene phenyl-sulfhydrates, 3- methylbenzene phenyl-sulfhydrates,
4- methoxybenzenethiols, 2- thionaphthols, 4- chlorothio-phenols, 4- bromo thiophenols or 4- fluoro thiophenols, mercaptan are 3- sulfydryl -2- fourths
Ketone, benzyl mercaptan, cyclohexanethiol, cyclopentyl mercaptan, 3- mercapto-propionates, 2- methyl thioglycolates or 2 mercaptopropionic acid second
Ester；
Chlorination reagent is chloro- 5, the 5- DMHs of 1,3- bis- or sym-closene；Solvent is dichloromethane or 1,2- dichloro
Ethane；
The reactions steps of the synthetic method are as follows：In the solvent that phosphite ester, thiophenol or mercaptan are added to chloride containing reagent,
It is stirred at room temperature 5~10 minutes, is reacted with " one kettle way "；Reaction process is monitored with gas-chromatography, after question response is complete,
Filtering reacting liquid, filtrate rotary evaporation is boiled off after solvent, then carries out pillar layer separation, obtains required group thiophosphate
Compound；
The phosphite ester, thiophenol or mercaptan, the mol ratio of chloro- 5, the 5- DMHs of 1,3- bis- are 1~1.2: 1: 0.5；
The phosphite ester, thiophenol or mercaptan, the mol ratio of sym-closene are 1: 1: 0.35.
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