CN113831288A - 一种硫代酰胺类衍生物、制备方法及应用 - Google Patents
一种硫代酰胺类衍生物、制备方法及应用 Download PDFInfo
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- 150000003556 thioamides Chemical class 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- -1 nitrogen-containing heterocyclic compound Chemical class 0.000 claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 150000001299 aldehydes Chemical class 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 5
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002496 methyl group Chemical class [H]C([H])([H])* 0.000 claims description 4
- 125000002560 nitrile group Chemical group 0.000 claims description 4
- 150000002825 nitriles Chemical class 0.000 claims description 4
- ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical compound O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 claims description 4
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 claims description 4
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 claims description 2
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 claims description 2
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 claims description 2
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 claims description 2
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 claims description 2
- VAUMDUIUEPIGHM-UHFFFAOYSA-N 5-Methyl-2-thiophenecarboxaldehyde Chemical compound CC1=CC=C(C=O)S1 VAUMDUIUEPIGHM-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 claims description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 abstract description 6
- 239000011593 sulfur Substances 0.000 abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000007142 ring opening reaction Methods 0.000 abstract description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 abstract description 2
- 239000012752 auxiliary agent Substances 0.000 abstract description 2
- 238000006477 desulfuration reaction Methods 0.000 abstract description 2
- 230000023556 desulfurization Effects 0.000 abstract description 2
- 239000003546 flue gas Substances 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 4
- QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical compound NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000001810 isothiocyanato group Chemical class *N=C=S 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000004763 sulfides Chemical class 0.000 description 1
- 125000001391 thioamide group Chemical group 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
Description
技术领域
本发明涉及化合物技术领域,进一步地说,是涉及一种硫代酰胺类衍生物、制备方法及应用。
背景技术
随着工业发展及人类活动的加大,以H2S气体排放量也逐渐增大。H2S排放量的增加破坏了自然界的生态平衡,也使人类生存环境受到了不断恶化的威胁。但同时H2S既是一种弱酸性的化合物,又是一种硫源,因此,将H2S清洁高效地转化为具有高附加值的化学品对解决环境污染、保持生态稳定有着重要的意义。
硫代酰胺是一类杂环类化合物的重要中间体,这类化合物又具有生物活性和药用活性,被广泛用于合成噻唑等硫代杂环类化合物;同时,硫代酰胺类化合物也可以作为配体在金属有机化学中的得以应用,又由于该类化合物中的杂原子富电子特性,可以作为荧光探针应用于材料科学等领域(Chem Rev.2003,103,197;AngewChemInt Ed.2010,49,2011;Tetrahedron 2018,74,4168;Chin.J.Org.Chem.2019,39,3542),因此,高效构建硫代酰胺结构的化合物成为了许多科研工作者的研究重点。
以腈、醛、肟、酰胺、伯胺、卤代炔或异硫腈酸酯等为原料,与硫磺、硫化钠、乙硫醇、二硫化碳、硫氢化钠或劳森试剂等硫化物为硫源进行反应,制备硫代酰胺类衍生物(Synth.Commun.2006,36,295;Tetrahedron2016,72,2012;Org.Lett.2018,20,2228;Adv.Synth.Catal.2019,361,1787),这类反应的明显缺点是使用的有机溶剂沸点较高,反应底物大大过量,废弃物较多,反应温度较高,有的需要使用氧化剂等,不仅反应成本高,而且对环境污染严重。
发明内容
为解决现有技术中出现的问题,本发明提供了一种硫代酰胺类衍生物、制备方法及应用。首次利用H2S为硫源,同时促进含氮杂环化合物开环,与醛类衍生物反应合成一类新型硫代酰胺类衍生物。
本发明的目的之一是提供一种硫代酰胺类衍生物,其特征在于:
所述硫代酰胺类衍生物的结构式为:
其中,R1选自噻吩基、呋喃基、吡咯基、吡啶基、苯基、苯基的邻位、间位或对位单取代或多取代甲基、卤素(F、Cl、Br、I)、甲氧基、腈基、二甲胺基、羟基中的一种或几种;优选选自噻吩基、呋喃基、吡咯基、吡啶基、苯基、苯基的邻位单取代羟基或对位单取代甲基、溴基、甲氧基、腈基、二甲胺基、羟基或二取代二甲氧基.
n为1到5的整数(包括1和5)。
本发明的目的之二是提供一种硫代酰胺类衍生物的制备方法。
所述方法包括:
醛类衍生物、含氮杂环化合物和溶剂加入反应釜,充入H2S进行反应,制得所述硫代酰胺类衍生物。
本发明的一种优选的实施方式中,
所述含氮杂环化合物的结构式为:
n为1到5的整数(包括1和5)。
本发明的一种优选的实施方式中,
所述醛类衍生物的结构式为:
R1选自噻吩基、呋喃基、吡咯基、吡啶基、苯基、苯基的邻位、间位或对位单取代或多取代甲基、卤素(F、Cl、Br、I)、甲氧基、腈基、二甲胺基、羟基中的一种或几种;
优选选自噻吩基、呋喃基、吡咯基、吡啶基、苯基、苯基的邻位单取代羟基或对位单取代甲基、溴基、甲氧基、腈基、二甲胺基、羟基或二取代二甲氧基。
本发明的一种优选的实施方式中,
所述醛类衍生物选自苯甲醛、对甲基苯甲醛、对氯苯甲醛、对羟基苯甲醛、对甲氧基苯甲醛、对二甲氨基苯甲醛、3,4-二甲氧基苯甲醛、对腈基苯甲醛、3-溴苯甲醛、2-羟基苯甲醛、3-噻吩甲醛、5-甲基-2-噻吩甲醛、2-呋喃甲醛、2-噻吩甲醛、2-吡啶甲醛、2-吡咯甲醛中的一种或组合。
本发明的一种优选的实施方式中,
所述溶剂选自N-甲基吡咯烷酮、四氢呋喃、水、聚乙二醇、二恶烷中的一种或组合。本发明的溶剂都是低沸点溶剂,方便后续处理。
含氮杂环化合物和溶剂的用量比为:1mmol:(1~4)mL。
本发明的一种优选的实施方式中,
所述含氮杂环化合物、醛类衍生物、H2S的摩尔用量比为1:(1~4):(1~5);
优选为:1:(1~4):(3~5);
本发明的一种优选的实施方式中,
反应温度为80~150℃;反应压力为0.2~1MPa;反应时间为12~36h。
制备方法具体如下:
在聚四氟乙烯内衬的不锈钢高压反应釜中依次加入醛类衍生物、含氮杂环化合物有机碱和溶剂,充入1~5mmol的H2S,控制反应温度为80~150℃,待反应完成后,冷却至室温,用乙酸乙酯溶解,减压除去溶剂得粗产物,粗产物经重结晶或柱层析分离得到一类新型硫代酰胺类衍生物。
本发明的目的之三是提供一种硫代酰胺类衍生物在医药、农业中的应用。
本发明与传统催化剂和反应工艺比较具有以下优点:
1、利用H2S为硫源,烟气脱硫产品,价格低廉易得。
2、反应体系相对简单,除原料外不加入其它任何助剂。
3、含氮杂环化合物为碱和亲核试剂,利用H2S促进含氮杂环化合物开环,与醛类衍生物反应合成目标产品,提高了原子经济性。
4、适合多种高附加值医药中间体的合成,且对每一种高附加值医药中间体均具有较强的底物适用性。
具体实施方式
下面结合具体实施例对本发明进行具体的描述,有必要在此指出的是以下实施例只用于对本发明的进一步说明,不能理解为对本发明保护范围的限制,本领域技术人员根据本发明内容对本发明做出的一些非本质的改进和调整仍属本发明的保护范围。
实施例中涉及的反应试剂均为常用的市售产品。实施例中使用的核磁共振波谱仪型号为Agilent 500MHz DD2。
实施例1~18:不同摩尔用量比合成N-(3-(2-氧代氮)丙基)硫代酰胺。
在15ml聚四氟乙烯内衬的反应釜中加入1mmol含氮杂环化合物(DBU1,8-二氮杂双环[5,4,0]十一碳-7-烯)、对应量的苯甲醛,再加入2mL THF作为反应溶剂,放入磁子,拧紧反应釜,然后通入相应量的H2S,在相应的温度下搅拌反应一定时间。将反应釜冷却至室温后,用乙酸乙酯溶解,减压除去溶剂得粗产物;粗产物经重结晶或柱层析分离(200-300目硅胶,石油醚和乙酸乙酯作洗脱剂)得到纯度大于99%的黄色粉末N-(3-(2-氧代氮)丙基)硫代苯甲酰胺。核磁表征数据:1H NMR(500MHz,CDCl3,TMS):δ(ppm)9.62(s,1H),7.95~7.93(m,2H),7.45~7.36(m,3H),3.87(q,J=5.0,5.5Hz,2H),3.46~3.42(m,2H),3.37~
3.35(m,2H),2.56~2.54(m,2H),1.90~1.85(m,2H),1.75~1.73(m,2H),1.69~1.65(m,4H),HRMS(ESI)m/z:291.1517[M+H]+。
表1给出不同摩尔用量比、反应温度、反应溶剂合成N-(3-(2-氧代氮)丙基)硫代酰胺的实验结果。
表1
实施例19~38:一类新型硫代苯甲酰胺类衍生物的合成
以下一类新型硫代苯甲酰胺类衍生物参照实施例2合成条件进行合成,相关数据列于表2-表3中。
表2
表3
说明:由于个别产物后处理较为困难,所以产率会较低些。但都经过谱图证明得到了所述产物。
Claims (10)
2.如权利要求1所述的硫代酰胺类衍生物,其特征在于:
R1选自噻吩基、呋喃基、吡咯基、吡啶基、苯基、苯基的邻位单取代羟基或对位单取代甲基、溴基、甲氧基、腈基、二甲胺基、羟基或二取代二甲氧基。
3.一种如权利要求1~2之一所述的硫代酰胺类衍生物的制备方法,其特征在于所述方法包括:
醛类衍生物、含氮杂环化合物和溶剂加入反应釜,充入H2S进行反应,制得所述硫代酰胺类衍生物。
6.如权利要求5所述的制备方法,其特征在于:
所述醛类衍生物选自苯甲醛、对甲基苯甲醛、对氯苯甲醛、对羟基苯甲醛、对甲氧基苯甲醛、对二甲氨基苯甲醛、3,4-二甲氧基苯甲醛、对腈基苯甲醛、3-溴苯甲醛、2-羟基苯甲醛、3-噻吩甲醛、5-甲基-2-噻吩甲醛、2-呋喃甲醛、2-噻吩甲醛、2-吡啶甲醛、2-吡咯甲醛中的一种或组合。
7.如权利要求3所述的制备方法,其特征在于:
所述溶剂选自N-甲基吡咯烷酮、四氢呋喃、水、聚乙二醇、二恶烷中的一种或组合。
8.如权利要求3所述的制备方法,其特征在于:
所述含氮杂环化合物、醛类衍生物、H2S的摩尔比为1:(1~4):(1~5);优选为1:(1~4):(3~5);
含氮杂环化合物和溶剂的用量比为:1mmol:(1~4)mL。
9.如权利要求3所述的制备方法,其特征在于:
反应温度为80~150℃;反应压力为0.2~1MPa;反应时间为12~36h。
10.一种如权利要求1~2之一所述的硫代酰胺类衍生物在医药、农业中的应用。
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