CN110903317A - 一种制备多取代偕二芳基甲基磷酸酯类化合物的方法 - Google Patents
一种制备多取代偕二芳基甲基磷酸酯类化合物的方法 Download PDFInfo
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- -1 phosphite compound Chemical class 0.000 claims abstract description 41
- 239000000047 product Substances 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 238000006477 desulfuration reaction Methods 0.000 claims abstract description 5
- 230000023556 desulfurization Effects 0.000 claims abstract description 5
- 238000000746 purification Methods 0.000 claims abstract description 3
- 238000000926 separation method Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
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- 238000004440 column chromatography Methods 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
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- 238000005954 phosphonylation reaction Methods 0.000 claims description 4
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- 239000002585 base Substances 0.000 claims description 3
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- QPKOILOWXGLVJS-UHFFFAOYSA-N bis(2-methylpropoxy)-oxophosphanium Chemical compound CC(C)CO[P+](=O)OCC(C)C QPKOILOWXGLVJS-UHFFFAOYSA-N 0.000 claims description 2
- OSPSWZSRKYCQPF-UHFFFAOYSA-N dibutoxy(oxo)phosphanium Chemical compound CCCCO[P+](=O)OCCCC OSPSWZSRKYCQPF-UHFFFAOYSA-N 0.000 claims description 2
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 claims description 2
- NFORZJQPTUSMRL-UHFFFAOYSA-N dipropan-2-yl hydrogen phosphite Chemical compound CC(C)OP(O)OC(C)C NFORZJQPTUSMRL-UHFFFAOYSA-N 0.000 claims description 2
- RQKYHDHLEMEVDR-UHFFFAOYSA-N oxo-bis(phenylmethoxy)phosphanium Chemical compound C=1C=CC=CC=1CO[P+](=O)OCC1=CC=CC=C1 RQKYHDHLEMEVDR-UHFFFAOYSA-N 0.000 claims description 2
- 150000008301 phosphite esters Chemical class 0.000 claims description 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
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- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 claims 1
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- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
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- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
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- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 238000006254 arylation reaction Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
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- 239000003480 eluent Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
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- CAAULPUQFIIOTL-UHFFFAOYSA-N methyl dihydrogen phosphate Chemical class COP(O)(O)=O CAAULPUQFIIOTL-UHFFFAOYSA-N 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000741 silica gel Chemical class 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- OQCOEVHYCWVHTP-UHFFFAOYSA-N (4-hydroxy-4-oxo-1,3,2,4lambda5-dioxazaphosphetidin-2-ium-2-ylidene)azanide Chemical compound [N-]=[N+]1OP(=O)(O1)O OQCOEVHYCWVHTP-UHFFFAOYSA-N 0.000 description 1
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 1
- RNFJDJUURJAICM-UHFFFAOYSA-N 2,2,4,4,6,6-hexaphenoxy-1,3,5-triaza-2$l^{5},4$l^{5},6$l^{5}-triphosphacyclohexa-1,3,5-triene Chemical compound N=1P(OC=2C=CC=CC=2)(OC=2C=CC=CC=2)=NP(OC=2C=CC=CC=2)(OC=2C=CC=CC=2)=NP=1(OC=1C=CC=CC=1)OC1=CC=CC=C1 RNFJDJUURJAICM-UHFFFAOYSA-N 0.000 description 1
- AAPRGJZEAGZCJC-UHFFFAOYSA-N 4-[(4-methylphenyl)sulfonyl-phenylmethyl]phenol Chemical compound C1(=CC=CC=C1)C(C1=CC=C(C=C1)O)S(=O)(=O)C1=CC=C(C)C=C1 AAPRGJZEAGZCJC-UHFFFAOYSA-N 0.000 description 1
- 102000005702 Calcium-Activated Potassium Channels Human genes 0.000 description 1
- 108010045489 Calcium-Activated Potassium Channels Proteins 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
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- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
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- 229910019142 PO4 Inorganic materials 0.000 description 1
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- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000003804 effect on potassium Effects 0.000 description 1
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- KFZUDNZQQCWGKF-UHFFFAOYSA-M sodium;4-methylbenzenesulfinate Chemical class [Na+].CC1=CC=C(S([O-])=O)C=C1 KFZUDNZQQCWGKF-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4056—Esters of arylalkanephosphonic acids
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Molecular Biology (AREA)
Abstract
本发明公开了一种如式（Ⅸ）所示的偕二芳基甲基磷酸酯类化合物的制备方法，偕二芳基甲基砜类化合物与亚磷酸酯类化合物在碱性条件下，发生脱硫膦酰化反应，生成偕二芳基甲基磷酸酯类化合物。该过程操作简单，无需使用金属试剂、高毒性或高危险性试剂。反应转化率高，原子经济性高，副产物少，产物易分离提纯，适用于工业化生产
Description
技术领域
本发明属于有机合成化学领域，涉及一种制备多取代偕二芳基甲基磷酸酯类化合物的方法。
背景技术
偕二芳基甲基磷酸酯类化合物作为一种非常重要的骨架结构，广泛应用于医药、手性配体、阻燃材料、光电材料等领域，也是制备烯烃的重要中间体。例如化合物TPMP-III-4 (Ⅰ) 可引起细胞周期阻滞，抑制微管蛋白聚合，分离癌细胞中线粒体束缚的己糖激酶，并且抑制钙依赖钾离子通道，从而诱导多种癌细胞死亡 (J. Am. Chem. Soc. 2008, 130,31, 10274-10281)。再如化合物 (Ⅱ) 被认为是人类前列腺酸磷酸酶最有效的抑制剂(Bioorg. Med. Chem. Lett. 1996, 6, 311-314)，又如化合物 (Ⅲ) 是一种潜在的抗氧化剂和抗癌药物 (Eur. J. Med. Chem. 2019, 184, 111735)，而化合物 (Ⅳ) 对钾离子通道有良好的调节作用(WO2005003143)。
基于偕二芳基甲基磷酸酯类化合物在众多领域中的突出作用，此类化合物的合成引起化学家的广泛关注。传统合成方法包括Plater等报道的芳基卤代物和亚磷酸三乙酯参与的Michaelis-Arbuzov reaction（Tetrahedron 2003, 59, 4673），该方法反应条件苛刻，芳基卤代物毒性和污染较大，对人体和环境有害。2013年，Pallikonda等报道了FeCl3催化的α-羟基磷酸酯与芳烃之间的傅-克芳基化反应，用于偕二芳基甲基磷酸酯类化合物的制备 (Eur. J. Org. Chem. 2013, 944)，但该方法只适用于含富电子芳烃的底物，局限性大。2019年Kim等发现BF3-Et2O可催化芳基醛，亚磷酸三乙酯和甲基苯基醚的一锅法多组分反应，合成出一系列甲基磷酸酯类化合物 (J. Org. Chem. 2019, 84, 6323−6336），该方法与Pallikonda等发展的方法相类似，底物范围窄小，仅局限于富电子芳烃。2017年Wang课题组报道了金属Rh (Ⅰ) 催化的α-重氮磷酸酯和芳基苯硼酸的芳基化反应，生成偕二芳基甲基磷酸酯化合物（Chin. J. Chem. 2017, 35, 621-627），尽管该反应收率优良，但芳基硼酸底物范围小且重氮化合物不稳定，限制了其实际应用。
为了克服上述缺陷，本方法旨在公开一种利用偕二芳基甲基砜类化合物与亚磷酸酯类化合物的脱硫膦酰化反应，制备偕二芳基甲基磷酸酯类化合物的方法，该方法原料廉价易得，无需使用金属催化剂和高毒性试剂，反应底物适用范围广，对比已有的方法，本方法步骤简洁，操作简单，应用性更好。
发明内容
本发明能弥补现有合成方法缺点，绿色，高效合成多取代偕二芳基甲基磷酸酯类化合物。
本发明采用碱性条件下，偕二芳基甲基砜类化合物与亚磷酸酯类化合物的脱硫膦酰化反应，以偕二芳基砜类化合物和亚磷酸酯类化合物为原料，合成如式 (IX) 所示的偕二芳基甲基磷酸酯类化合物，其中R1为叔丁基、甲基、异丙基、氢原子、溴原子、甲氧基，R2为叔丁基、甲基、异丙基、氢原子、溴原子、甲氧基，R3为4-氟苯基、2-甲基苯基、4-硝基苯基、4-氰基苯基、4-甲氧基苯基、2-三氟甲基苯基、2-萘基、环己基等基团，R4为甲氧基、乙氧基、异丙氧基、苯基等。
所述制备方法，如反应过程式 (Ⅹ) 所示：
过程式 (Ⅹ) 中R1为叔丁基、甲基、异丙基、氢原子、溴原子、甲氧基，R2为叔丁基、甲基、异丙基、氢原子、溴原子、甲氧基，R3为4-氟苯基、2-甲基苯基、4-硝基苯基、4-氰基苯基、4-甲氧基苯基、2-三氟甲基苯基、2-萘基、环己基等基团，R4为甲氧基、乙氧基、异丙氧基、苯基等。
其中，所述偕二芳基甲基砜类化合物、亚磷酸酯、碱的摩尔比为1:1.2:1.2。
其中，所述偕二芳基甲基砜类化合物如式 (XI) 所示，R1为叔丁基、甲基、异丙基、氢原子、溴原子、甲氧基，R2为叔丁基、甲基、异丙基、氢原子、溴原子、甲氧基，R3为4-氟苯基、2-甲基苯基、4-硝基苯基、4-氰基苯基、4-甲氧基苯基、2-三氟甲基苯基、2-萘基、环己基等基团。
其中，所述亚磷酸酯类化合物为亚磷酸二甲酯、亚磷酸二乙酯、亚磷酸二异丙酯、亚磷酸二正丁酯、亚磷酸二异丁酯、亚磷酸二苄酯、二苯氧磷。
其中，所述碱为DBU、Cs2CO3、K2CO3、Na2CO3等。
本发明具体制备方法包括：将偕二芳基甲基砜类化合物加入反应瓶，再加入碱和有机溶剂，然后加入亚磷酸酯类化合物，55°C下反应6h。用薄层色谱检测反应至原料消耗完全后，将产物倒入水中洗涤，用二氯甲烷萃取混合物并分液，用无水硫酸钠干燥有机相，过滤后旋转蒸发除去溶剂得到粗品。粗产品经柱层析法提纯，得到目标化合物。
本发明所述有机溶剂是二甲基亚砜、二氯甲烷、四氢呋喃、二甲基甲酰胺，所用溶剂经市面购得，无任何前处理。
本发明所使用偕二芳基甲基砜类化合物所使用原料合成请参考 (TetrahedronLett, 2019, 60, 244-247; Org. Chem. Front. 2018, 5, 1820-1824)。
本发明所使用取代苯酚，哌啶，醛，格式试剂，对甲苯亚磺酸钠，碱，无水硫酸钠，有机溶剂，硅胶，硅胶板均可由市面购得。
本发明的目的是在于提供一种原料廉价易得，操作简单的偕二芳基甲基磷酸酯类化合物的制备方法。为了达到上述目的，本发明利用碱性条件下，偕二芳基甲基砜类化合物与亚磷酸酯类化合物之间的脱硫膦酰化反应，一锅法制备偕二芳基甲基磷酸酯类化合物。该过程操作简单，无需使用金属试剂、高毒性或高危险性试剂。反应转化率高，原子经济性高，副产物少，产物易分离提纯。同时，所得产物易于进一步衍生，附加值高。
具体实施方式
结合以下具体实施例，对本发明作进一步的详细说明，本发明的保护内容不局限于以下实施例。 在不背离发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。 实施本发明的过程、条件、试剂、实验方法等，除以下专门提及的内容之外，均为本领域的普遍知识和公知常识，本发明没有特别限制内容。
本发明提出的过程式 (Ⅹ) 所示取代甲基磷酸酯化合物具体制备方法具体步骤包括：先称取偕二芳基甲基砜类化合物与碱的摩尔比为1:1.2 加入反应瓶中，再加入溶剂用量为 4 mL/mmol，加入亚磷酸酯类化合物用量为 1.2当量。55 ℃下搅拌反应，用薄层色谱检测反应至原料消耗完全，将反应体系倾倒入水并洗涤，然后用二氯甲烷萃取三次，再用无水硫酸钠干燥有机相，过滤后旋转蒸发除去溶剂得到粗品。所得粗品通过柱层析(洗脱剂为乙酸乙酯:石油醚体积比=1:4-1:1)，得到所述偕二芳基甲基磷酸酯类化合物。
实施例1制备化合物制备二乙基((4-羟基苯基)(苯基)甲基)磷酸酯 (3a)：称取4-((苯基)(对甲苯磺酰基)甲基)苯酚(0.25 mmol)，碳酸铯(0.3 mmol)，加入反应瓶中，加入1mL DMSO，加入亚磷酸二乙酯(0.3 mmol)。55 ℃下搅拌反应，用薄层色谱检测反应至原料消耗完全，将反应后产物倾倒入水中，洗涤，二氯甲烷10 mL×3萃取，用无水硫酸钠干燥有机相，过滤后旋转蒸发除去溶剂得到粗品。所得粗品通过柱层析(洗脱剂为乙酸乙酯: 石油醚体积比=1:1)，得到所述偕二芳基甲基磷酸酯类化合物3a纯品收率65%，见表1。
二乙基((4-羟基苯基)(苯基)甲基)磷酸酯3a的表征为:1H NMR (600 MHz, ) δ8.30 (s, 1H), 7.50 (d, J = 7.8 Hz, 2H), 7.30 (t, J = 7.6 Hz, 2H), 7.27-7.20(m, 3H), 6.71 (d, J = 8.4 Hz, 2H), 4.38 (d, J P-H = 25.4 Hz, 1H), 3.98 (dp, J P-H = 10.1, 7.1 Hz, 2H), 3.90-3.78 (m, 2H), 1.12 (dt, J P-H = 9.9, 7.1 Hz, 6H). 13CNMR (151 MHz, CDCl3 ) δ 156.22 (d, J C-P = 1.8 Hz), 136.94 (d, J C-P = 4.5 Hz),130.44 (d, J C-P = 7.7 Hz), 129.42 (d, J C-P = 8.6 Hz), 128.57 (s), 127.09 (s),126.97 (d, J C-P = 5.7 Hz), 115.98 (s), 62.96 (dd, J C-P = 14.2, 7.5 Hz), 50.38(d, J C-P = 139.4 Hz), 16.22 (t, J C-P = 6.4 Hz)。
实施例2-14 制备化合物(3b~3n)。
实施例2-14同实施例1.反应中取代基的变化、化合物编号、产率等见表1。
表1
偕二芳基甲基磷酸酯类化合物3b~3n的表征如下:。
产物3b的表征:1H NMR (600 MHz, CDCl3) δ 7.51 (d, J = 7.8 Hz, 2H), 7.32(t, J = 7.6 Hz, 2H), 7.29-7.22 (m, 1H), 6.80 (d, J = 1.5 Hz, 2H), 5.52 (s,1H), 4.35 (d, J P-H = 25.3 Hz, 1H), 3.87 (s, 6H), 3.59 (d, J P-H = 10.7 Hz, 3H),3.54 (d, J P-H = 10.7 Hz, 3H). 13C NMR (151 MHz, ) δ 147.10 (s), 136.75 (d, J C-P=5.3 Hz), 134.23 (s), 129.21 (d, J C-P = 7.8 Hz), 128.67 (s), 127.42 (d, J C-P =5.0 Hz), 127.27 (d, J C-P = 2.0 Hz), 106.49 (d, J C-P = 8.6 Hz), 56.39 (s), 53.46(d, J C-P = 6.8 Hz), 53.36 (d, J C-P = 7.0 Hz), 50.64 (d, J C-P = 139.2 Hz)。
产物3c的表征:1H NMR (600 MHz, CDCl3) δ 7.73-7.67 (m, 2H), 7.58 (d, J =8.0 Hz, 2H), 7.50-7.44 (m, 2H), 7.4-7.32 (m, 4H), 7.30-7.25 (m, 2H), 7.21 (t,J = 7.6 Hz, 2H), 7.16-7.12 (m, 1H), 7.08 (d, J P-H = 1.5 Hz, 2H), 5.04 (s, 1H),4.65 (d, J P-H = 9.7 Hz, 1H), 1.29 (s, 18H)。
产物3d的表征:1H NMR (600 MHz, ) δ 7.94 (s,1H), 7.50 (d, J = 7.7 Hz,2H), 7.31 (t, J = 7.6 Hz,2H), 7.25 (ddd, J = 12.3, 8.1, 4.6 Hz,3H), 6.72 (d,J = 8.3 Hz,2H), 4.41 (d, J P-H = 25.4 Hz,1H), 3.57 (dd, J P-H = 10.7, 7.0 Hz,6H).13C NMR (151 MHz, CDCl3) δ 156.22 (d, J C-P = 1.8 Hz), 136.60 (d, J C-P = 5.1 Hz),130.43 (d, J C-P = 7.9 Hz), 129.34 (d, J C-P = 8.7 Hz), 128.71 (s), 127.26 (d,J C-P = 1.5 Hz), 126.72 (d, J C-P = 5.9 Hz), 116.07 (d, J C-P = 1.2 Hz), 54.84 –51.96 (m), 49.88 (d, J C-P = 139.4 Hz)。
产物3e的表征:1H NMR (600 MHz, ) δ 8.11 (s, 1H), 7.41 (d, J = 7.6 Hz,2H), 7.29- 7.16 (m, 3H), 6.85 (d, J = 8.5 Hz, 2H), 6.72 (d, J = 8.4 Hz, 2H),4.36 (d, J P-H = 25.6 Hz, 1H), 3.77 (s, 3H), 3.57 (d, J P-H = 10.7 Hz, 6H).13C NMR(151 MHz, CDCl3) δ 158.86 (d, J = 1.6 Hz), 156.20 (d, J = 2.1 Hz), 130.49 (d,J = 8.1 Hz), 130.41 (d, J = 7.7 Hz), 128.68 (d, J = 5.1 Hz), 127.17 (d, J =5.3 Hz), 116.11 (s), 114.24 (s), 55.33 (s), 53.66 (dd, J C-P = 16.8, 7.0 Hz),49.02 (d, J C-P = 139.5 Hz)。
产物3f的表征:1H NMR (600 MHz, ) δ 8.18 (d, J = 6.9 Hz, 1H), 8.00 (d,J = 8.1 Hz, 1H), 7.81 (dd, J = 26.6, 7.9 Hz, 3H), 7.51 (t, J = 7.7 Hz, 1H),7.49-7.40 (m, 3H), 7.26 (d, J = 9.0 Hz, 2H), 6.66 (d, J = 8.3 Hz, 1H), 5.24(d, J P-H = 26.7 Hz, 1H), 3.57 (dd, J P-H = 17.7, 10.8 Hz, 6H). 13C NMR (151 MHz,DMSO(d6)) δ 156.85 (d, J C-P = 2.1 Hz), 134.15 (d, J C-P = 22.9 Hz), 131.57 (d,J C-P = 12.1 Hz), 130.96 (d, J C-P = 6.8 Hz), 129.23 (s), 128.06 (s), 127.11 (t,J C-P = 6.3 Hz), 126.88 (s), 126.17 (s), 125.81 (s), 124.10 (s), 115.62 (s),53.41 (dd, J C-P = 56.9, 6.9 Hz), 43.23 (d, J C-P = 139.3 Hz)。
产物3g的表征:1H NMR (600 MHz, ) δ 7.92 (d, J = 7.7 Hz, 1H), 7.56(brs, 1H), 7.30-7.22 (m, 1H), 7.21-7.11 (m, 4H), 6.67 (d, J = 8.4 Hz, 2H),4.62 (d, J P-H = 26.2 Hz, 1H), 3.58 (dd, J P-H = 10.7, 1.3 Hz, 6H), 2.28 (s, 3H).13C NMR (151 MHz, ) δ 156.13 (d, J C-P = 3.1 Hz), 136.43 (d, J C-P = 12.3 Hz),134.99 (d, J C-P = 2.6 Hz), 130.80 (d, J C-P = 13.2 Hz), 130.71 (s), 129.11 (d,J C-P = 5.5 Hz), 127.28 (s), 126.27 (s), 125.83 (d, J C-P = 6.2 Hz), 116.06 (d,J C-P = 2.0 Hz), 53.61 (d, J C-P = 7.4 Hz), 53.51 (d, J C-P = 7.5 Hz), 45.52 (d,J C-P = 140.9 Hz), 19.85 (s)。
产物3h的表征:1H NMR (600 MHz, ) δ 8.08 (s, 1H), 7.74 (d, J = 7.7 Hz,1H), 7.70 (s, 1H), 7.52 (d, J = 7.7 Hz, 1H), 7.45 (t, J = 7.8 Hz, 1H), 7.26(d, J = 8.6 Hz, 2H), 6.76 (d, J = 8.5 Hz, 2H), 4.47 (d, J P-H = 25.5 Hz, 1H),3.60 (dd, J P-H = 14.8, 10.8 Hz, 6H). 13C NMR (151 MHz, ) δ 156.56 (d, J C-P = 2.0Hz), 137.87 (d, J C-P = 4.4 Hz), 132.67 (d, J C-P = 7.7 Hz), 131.11 (q, J C-F =32.4 Hz), 130.57 (d, J C-P = 7.8 Hz), 129.28 (s), 126.33-126.05 (m), 125.97 (d,J C-P = 6.0 Hz), 124.24 (d, J C-P = 2.4 Hz), δ 124.07 (q, J C-F = 272.5 Hz).116.27(s), 53.79 (dd, J C-P = 37.6, 7.5 Hz), 49.69 (d, J C-P = 140.0 Hz)。
产物3i的表征:1H NMR (600 MHz, CDCl3) δ 7.49 (ddd, J = 8.4, 5.3, 1.6Hz, 2H), 7.28 (d, J P-H = 1.6 Hz, 2H), 7.01 (t, J = 8.6 Hz, 2H), 5.21 (s, 1H),4.35 (d, J P-H = 25.4 Hz, 1H), 3.55 (d, J P-H = 10.6 Hz, 3H), 3.52 (d, J P-H = 10.6Hz, 3H), 1.42 (s, 18H); 13C NMR (151 MHz, CDCl3) δ 161.97 (dd, J C-F,C-P = 245.7,2.4 Hz), 153.08 (d, J C-P = 1.9 Hz), 136.16 (d, J C-P = 3.1 Hz), 133.59 -132.65(m), 130.98 (t, J C-F,C-P = 7.9 Hz), 126.65 (d, J C-P = 5.2 Hz), 125.98 (d, J =7.8 Hz), 115.40 (d, J C-F = 22.0 Hz), 53.45 (d, J C-P = 7.5 Hz), 53.11 (d, J C-P =7.5 Hz), 49.79 (d, J C-P = 138.6 Hz), 34.43 (s), 30.24 (s)。
产物3j的表征:1H NMR (600 MHz, CDCl3) δ 7.92 (d, J = 7.8 Hz, 1H), 7.28(d, J P-H = 1.5 Hz, 2H), 7.24-7.20 (m, 1H), 7.14 (d, J = 4.3 Hz, 2H), 5.13 (s,1H), 4.61 (d, J P-H = 26.1 Hz, 1H), 3.52 (d, J P-H = 2.2 Hz, 3H), 3.51 (d, J P-H =2.3 Hz, 3H), 2.36 (s, 3H), 1.40 (s, 18H); 13C NMR (151 MHz, CDCl3) δ 152.88(d, J C-P = 3.0 Hz), 136.17 (d, J C-P = 12.2 Hz), 135.90 (d, J C-P = 1.6 Hz),135.67 (d, J C-P = 3.3 Hz), 130.61 (s), 129.33 (d, J C-P = 5.5 Hz), 126.97 (s),126.44 (d, J C-P = 5.6 Hz), 126.34 (d, J C-P = 7.7 Hz), 126.19 (d, J C-P = 2.1 Hz),53.27 (d, J C-P = 7.3 Hz), 53.12 (d, J C-P = 6.6 Hz), 45.89 (d, J C-P = 138.8 Hz),34.37 (s), 30.39 (s), 20.08 (s)。
产物3k的表征:1H NMR (600 MHz, CDCl3) δ 8.18 (d, J = 8.4 Hz, 2H), 7.69(dd, J = 8.8, 1.8 Hz, 2H), 7.28 (d, J P-H = 1.8 Hz, 2H), 5.22 (s, 1H), 4.46 (d,J P-H = 25.3 Hz, 1H), 3.61 (d, J P-H = 10.8 Hz, 3H), 3.53 (d, J P-H = 10.7 Hz, 3H),1.42 (s, 18H)。
产物3l的表征:1H NMR (600 MHz, CDCl3) δ 7.62 (q, J P-H = 8.7 Hz), 7.26(s), 5.21 (s), 4.40 (d, J P-H = 25.3 Hz), 3.59 (d, J P-H = 10.8 Hz), 3.52 (d, J P-H = 10.6 Hz), 1.42 (s); 13C NMR (151 MHz, CDCl3) δ 153.38 (d, J C-P = 2.2 Hz),142.92 (d, J C-P = 5.2 Hz), 136.42 (s), 132.32 (s), 130.14 (d, J C-P = 7.8 Hz),126.04 (d, J C-P = 7.8 Hz), 125.50 (d, J C-P = 5.8 Hz), 118.73 (s), 110.99 (d,J C-P = 1.5 Hz), 53.78 (d, J C-P = 7.1 Hz), 53.07 (d, J C-P = 7.6 Hz), 50.69 (d,J C-P = 138.6 Hz), 34.45 (s), 30.29 (s)。
产物3m的表征:1H NMR (600 MHz, CDCl3) δ 8.26 (d, J = 8.0 Hz, 1H), 7.65(d, J = 7.9 Hz, 1H), 7.57 (t, J = 7.7 Hz, 1H), 7.41 (s, 2H), 7.34 (t, J = 7.6Hz, 1H), 5.16 (s, 1H), 4.78 (d, J P-H = 26.2 Hz, 1H), 3.52 (d, J P-H = 10.6 Hz,3H), 3.50 (d, J P-H = 10.7 Hz, 3H), 1.41 (s, 18H); 13C NMR (151 MHz, CDCl3) δ153.12 (d, J C-P =1.8 Hz), 136.25 (s), 135.99 (s), 131.93 (s), 131.62 (d, J C-P =5.4 Hz), 128.39 (qd, J C-F,C-P = 28.6, 10.0 Hz), 127.00 (s), 126.23 (d, J C-P =5.4 Hz), 126.19 (d, J C-P = 7.1 Hz), 126.14 (d, J C-P = 8.3 Hz), 124.45 (q, J C-F =273.9 Hz), 53.61 (d, J C-P = 7.0 Hz), 53.09 (d, J C-P = 7.2 Hz), 45.02 (d, J C-P =139.4 Hz), 34.42 (s), 30.28 (s)。
产物3n的表征:1H NMR (600 MHz, CDCl3) δ 7.97 (s, 1H), 7.85-7.77 (m,3H), 7.67 (d, J = 8.5 Hz, 1H), 7.49-7.41 (m, 2H), 7.38 (d, J P-H = 1.5 Hz, 2H),5.14 (s, 1H), 4.53 (d, J P-H = 25.3 Hz, 1H), 3.54 (t, J P-H = 11.0 Hz, 6H), 1.41(s, 18H); 13C NMR (151 MHz, CDCl3) δ 153.04 (d, J C-P = 2.1 Hz), 136.04 (s),134.77 (d, J C-P = 5.4 Hz), 133.50 (s), 132.48 (s), 128.24 (s), 128.17 (d, J C-P = 1.7 Hz), 128.01 (s), 127.57 (s), 127.52 (s), 126.81 (d, J C-P = 5.3 Hz),126.15 (d, J C-P = 7.7 Hz), 126.04 (s), 125.84 (s), 53.43 (d, J C-P = 6.8 Hz),53.21 (d, J C-P = 7.4 Hz), 50.81 (d, J C-P = 138.4 Hz), 34.43 (s), 30.34 (s)。
最后说明的是，以上优选实施例仅用以说明本发明的技术方案而非限制，尽管通过上述优选实施例已经对本发明进行了详细的描述，但本领域技术人员应当理解，可以在形式上和细节上对其做出各种各样的改变，而不偏离本发明权利要求书所限定的范围。
Claims (5)
1.偕二芳基甲基磷酸酯类化合物的制备方法，是利用碱催化下的偕二芳基甲基砜类化合物与亚磷酸酯类化合物之间的脱硫膦酰化反应，得到如式（Ⅸ）所示的偕二芳基甲基磷酸酯类化合物；
所述制备方法反应式如式 (Ⅹ) 所示:
其中R1为叔丁基、甲基、异丙基、氢原子、溴原子、甲氧基；R2为叔丁基、甲基、异丙基、氢原子、溴原子、甲氧基；R3为苯基，2-氟苯基，3-氟苯基，4-氟苯基，2-溴苯基，3-溴苯基，4-溴苯基，2-甲基苯基，3-甲基苯基，4-甲基苯基，2-氯苯基，3-氯苯基，4-氯苯基，2-甲氧基苯基，3-甲氧基苯基，4-甲氧基苯基，4-硝基苯基，4-氰基苯基，2-萘基，2-吡啶基，2-三氟甲基苯基，3-三氟甲基苯基，4-三氟甲基苯基，2，4-二氯苯基，1，3-二氢异苯并呋喃基，4-叔丁基苯基，1-萘基苯基，环己基；R4为甲氧基，乙氧基，异丙氧基，正丁氧基，异丁氧基，苄氧基，苯基。
2.如权利要求1所述的制备方法，其特征在于，偕二芳基甲基砜类化合物、亚磷酸酯、碱的摩尔比为1:1.2:1.2。
3.如权利要求1所述的制备方法，其特征在于，所述碱为有机碱或无机碱；亚磷酸酯类化合物是亚磷酸二甲酯、亚磷酸二乙酯、亚磷酸二异丙酯、亚磷酸二正丁酯、亚磷酸二异丁酯、亚磷酸二苄酯、二苯氧磷。
4.如权利要求1所述的制备方法，其特征在于将偕二芳基甲基砜类化合物加入反应瓶，再加入碱和有机溶剂，然后加入亚磷酸酯类化合物，有机溶剂用量为4 mL/mmol 偕二芳基甲基砜类化合物，55℃下反应6h，用薄层色谱检测反应进程，反应完毕后，倒入水中洗涤，再加入二氯甲烷萃取，分液后干燥，旋蒸浓缩得粗产物，使用柱层析法提纯得到纯品。
5.如权利要求1所述的制备方法，其特征在于，所述制备方法的收率为44%-97%。
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| 尤鹏盛等: "偕二芳基甲基磷酸酯类化合物的合成新方法", 《中国科技论文在线》 * |
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