CN117069612A - Novel method for synthesizing cyanoacrylate - Google Patents
Novel method for synthesizing cyanoacrylate Download PDFInfo
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- CN117069612A CN117069612A CN202310859852.5A CN202310859852A CN117069612A CN 117069612 A CN117069612 A CN 117069612A CN 202310859852 A CN202310859852 A CN 202310859852A CN 117069612 A CN117069612 A CN 117069612A
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- etoac
- cyanoacrylate
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- cdcl
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- 229920001651 Cyanoacrylate Polymers 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 24
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 172
- -1 p-methylene Chemical group 0.000 claims abstract description 49
- 238000006243 chemical reaction Methods 0.000 claims abstract description 41
- MLIREBYILWEBDM-UHFFFAOYSA-M 2-cyanoacetate Chemical compound [O-]C(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-M 0.000 claims abstract description 39
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000000203 mixture Substances 0.000 claims abstract description 38
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 35
- NLCKLZIHJQEMCU-UHFFFAOYSA-N cyano prop-2-enoate Chemical class C=CC(=O)OC#N NLCKLZIHJQEMCU-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- AZQWKYJCGOJGHM-UHFFFAOYSA-N para-benzoquinone Natural products O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000003960 organic solvent Substances 0.000 claims abstract description 3
- 235000019439 ethyl acetate Nutrition 0.000 claims description 80
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 68
- 238000004440 column chromatography Methods 0.000 claims description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 238000003786 synthesis reaction Methods 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000012074 organic phase Substances 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims description 2
- DKCPKDPYUFEZCP-UHFFFAOYSA-N 2,6-di-tert-butylphenol Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=C1O DKCPKDPYUFEZCP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 238000013461 design Methods 0.000 abstract description 2
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 62
- 239000012043 crude product Substances 0.000 description 31
- 239000011734 sodium Substances 0.000 description 30
- 239000000047 product Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- IJVRPNIWWODHHA-UHFFFAOYSA-N 2-cyanoprop-2-enoic acid Chemical compound OC(=O)C(=C)C#N IJVRPNIWWODHHA-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application discloses a novel method for synthesizing cyanoacrylate, which comprises the following steps: s1, adding a p-methylene quinone compound, cyanoacetate, elemental sulfur, an organic solvent and alkali into a reaction container, and stirring at a high temperature; s2, after the reaction is finished, adding saturated sodium bicarbonate and ethyl acetate to dilute the mixture, stirring, extracting, separating and purifying to obtain cyanoacrylate compounds; the application adopts a high-efficiency route without metal catalysis, the synthetic route is novel in design, the operation method is simple, and the product can be directly obtained by reaction under mild conditions.
Description
Technical Field
The application relates to the technical field of compound synthesis, in particular to a novel method for synthesizing cyanoacrylate.
Background
Cyanoacrylates have a wide range of biological activities, and are commonly used in the fields of herbicides, insecticides, bactericides and the like, and the herbicidal activity thereof is one of the hot spots in the current herbicide research field. In addition, cyanoacrylates are frequently used as monomers for the synthesis of polymers, and are widely used in materials science as adhesives and support materials. In addition to these widespread applications, cyanoacrylates have been used for the synthesis of such cyano equivalents as primary amines, tetrazoles, aldehydes/ketones, acrylic acid derivatives and related functional groups. The synthesis and bioactivity studies of 2-cyanoacrylate chiral derivatives in Guizhou university 2006, the role of various cyanoacrylate derivatives is described in detail.
Classical synthetic routes to cyanoacrylate derivatives involve two methods, namely by using cyanoacetate, carbon disulphide, nucleophile and methylating agent as substrates under basic conditions, or by reacting under acidic conditions (e.g. TiCl 4 ) Using aldehyde/ketone and cyanoacetate as raw materials. Although these methods have been widely used in the field of synthesizing cyanoacrylate derivatives, they have been plagued by limitations such as a range of application of substrates, stability, toxicity, serious environmental pollution problems, laborious post-experimental treatments, and single molecular structure of the products. Therefore, there is a great need and a need to develop new strategies to improve the previous methods of synthesizing cyanoacrylate derivatives, and to accommodate the social development needs.
Disclosure of Invention
Aiming at the problems, the application provides a novel method for synthesizing cyanoacrylate, which is simple to operate, mild in reaction condition and nontoxic.
To achieve the purpose, the application provides the following technical scheme:
the application provides a novel method for synthesizing cyanoacrylate, which comprises the following steps:
s1, adding a p-methylene quinone compound, cyanoacetate and elemental sulfur (S) 8 ) Stirring the mixture at a high temperature;
s2, after the reaction is finished, adding saturated sodium bicarbonate and ethyl acetate to dilute the mixture, stirring, extracting, separating and purifying to obtain the cyanoacrylate compound.
Preferably, in step S1, the preparation method of the p-methylenequinone compound includes: 2, 6-di-tert-butylphenol/2, 6-diisopropylphenol, benzaldehyde with different substituents, toluene, piperidine and acetic anhydride are mixed and reacted in a reflux system.
Preferably, the p-methylenequinone compound has the chemical formula:
wherein R is 1 Including t-butyl, isopropyl; r is R 2 Electron withdrawing and donating groups including methyl, methoxy, isopropyl, N-dimethyl, nitro, cyano, fluoro, bromo, and di-and tri-substituted (chloro), and heterocycles of pyridine, thiophene, naphthalene;
and, the chemical reaction formula of step S1 is:
wherein R is 1 Including t-butyl, isopropyl; r is R 2 Electron withdrawing and donating groups including methyl, methoxy, isopropyl, N-dimethyl, nitro, cyano, fluoro, bromo, and di-and tri-substituted (chloro), and heterocycles of pyridine, thiophene, naphthalene; r is R 3 Including methyl, ethyl, t-butyl.
Preferably, in step S1, the organic solvent includes N, N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO), toluene, 1, 4-dioxane.
Preferably, in step S1, the base comprises potassium carbonate, triethylamine, potassium hydroxide, 1, 4-diazabicyclo [2.2.2] octane (DABCO), 1, 8-diazabicyclo undec-7-ene (DBU), sodium bicarbonate, potassium acetate.
Preferably, in step S1, the molar ratio of the methylenequinone compound, the cyanoacetate, the elemental sulfur (S8), and the base is (1-2): (1-2): (0.25-0.5): (1-2); further preferably, the molar ratio of the p-methylenequinone (p-QMs), the cyanoacetate, the elemental sulfur, the base, is 1:1:4:1.
preferably, in the step S1, stirring is carried out for 6-10 hours at 90-120 ℃; further preferably, the temperature is 100℃and the time is 8 hours.
Preferably, in step S2, the organic phase obtained by the separation of the extracts is washed with saturated sodium bicarbonate and the aqueous phase is washed with ethyl acetate.
Preferably, in step S2, the organic phase obtained by the separation of the extract is dried over anhydrous sodium sulfate, concentrated, and then separated and purified.
Preferably, the method of extraction comprises:
r1, extracted with a low concentration of EtOAc,
r2, extracted with high concentration EtOAc;
r3, washing an organic phase obtained by extracting and separating the liquid by using saturated sodium bicarbonate, and washing a water phase by using ethyl acetate;
the organic phase R4 was dried over anhydrous sodium sulfate and concentrated.
Preferably, the concentration of high concentration EtOAc is 3 times that of low concentration EtOAc.
Preferably, in the step S2, the separation and purification is column chromatography separation and purification, and the eluent is a mixture of petroleum ether and ethyl acetate; further preferably, the volume ratio of petroleum ether to ethyl acetate is 30:1.
preferably, a novel method for synthesizing cyanoacrylate has the chemical reaction formula:
into a dry 25ml flask were successively added p-methylenequinones (p-QMs), cyanoacetate, elemental sulfur (S) 8 ) The mixture was stirred at 100 ℃ until reaction was complete, ethyl acetate (EtOAc) and saturated sodium bicarbonate were added, stirred, separated into two layers, extracted with EtOAc, and the crude product was isolated by column chromatography to give the corresponding cyanoacrylate.
Compared with the prior art, the technical scheme of the application has the beneficial effects and remarkable progress that:
1. compared with the prior art, the novel method for synthesizing the cyanoacrylate has wider applicability, adopts a high-efficiency route without metal catalysis, has novel synthetic route design, is simple in operation method and can directly obtain a product through mild condition reaction;
2. the method expands the synthetic route of the cyanoacrylate, obtains more compound with rich structure, and has important significance on the synthetic route of the cyanoacrylate.
Drawings
FIG. 1 is a single crystal plot of the product of example 1, tert-butyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3-phenylacrylate;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3-phenylacrylate which is the product of example 1;
FIG. 3 is a nuclear magnetic resonance spectrum of ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3-phenylacrylate, which is the product of example 1.
Detailed Description
The application is further illustrated below in connection with specific examples. The examples are only for illustrating the present application and are not intended to limit the scope of the present application. Further, it is understood that various changes and modifications may be made by those skilled in the art after reading the disclosure herein, and such equivalents are intended to fall within the scope of the application as defined by the appended claims.
Example 1
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3-phenylacrylate in 90% yield. Single crystal spectrogram, nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum of 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3-phenyl ethyl acrylate are shown in figures 1-3 respectively。
1 H NMR(400MHz,CDCl 3 )δ7.49–7.33(m,4H),7.27(d,J＝13.6Hz,2H),7.18(d,J＝6.9Hz,1H),5.71(s,1H),4.16–4.07(m,2H),1.38(d,J＝5.6Hz,18H),1.16–1.07(m,3H). 13 C NMR(101MHz,CDCl 3 )δ170.42,163.54,157.51,135.70,130.08,129.51,129.12,128.77,128.32,127.98,127.79,118.13,100.68,61.80,34.32,29.93,13.79.HRMS:calcd.for C 27 H 33 NO 3 [M+Na]+428.2196；found 428.2195.
Example 2
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (p-tolyl) acrylate in 80% yield.
1 H NMR(400MHz,CDCl 3 )δ7.35–7.25(m,2H),7.20(dd,J＝16.9,7.9Hz,2H),7.09–6.94(m,2H),5.69(s,1H),4.14(p,J＝7.0Hz,2H),2.41(d,J＝2.2Hz,3H),1.38(d,J＝6.2Hz,18H),1.15(dt,J＝14.5,7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ171.04,163.77,157.48,136.31,135.57,130.95,129.86,129.34,128.90,128.72,118.41,99.97,61.79,34.32,30.14,21.58,13.88.HRMS:calcd.for C 27 H 33 NO 3 [M+Na]+442.2352；found 442.2351.
Example 3
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml)), stirring the mixture at 100deg.C until the reaction is complete, adding EtOAc (5 ml) and saturated sodium bicarbonate (5 ml), stirring, separating into two layers, extracting with EtOAc, then extracting with EtOAc (3X 15 ml), separating the crude product by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (m-tolyl) acrylate in 74% yield.
1 H NMR(400MHz,CDCl 3 )δ7.31–7.17(m,4H),7.01–6.94(m,2H),5.70(s,1H),4.13(p,J＝7.1Hz,2H),2.36(d,J＝11.7Hz,3H),1.38(d,J＝6.2Hz,18H),1.13(td,J＝7.1,4.5Hz,3H).13C NMR(101MHz,CDCl 3 )δ170.66,163.68,157.47,139.27,137.63,135.59,130.93,130.04,128.78,127.88,126.76,118.23,100.50,61.79,34.51,30.19,21.33.HRMS:calcd.for C 27 H 33 NO 3 [M+Na]+442.2352；found 442.2351.
Example 4
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (4-isopropyl) acrylate in 72% yield.
1 H NMR(400MHz,CDCl 3 )δ7.34(dd,J＝22.0,8.0Hz,1H),7.28–7.07(m,4H),6.95(s,1H),5.68(s,1H),4.12(qd,J＝7.1,3.7Hz,2H),2.96(p,J＝6.9Hz,1H),1.38(d,J＝4.5Hz,18H),1.31–1.24(m,6H),1.10(dt,J＝12.6,7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ170.68,163.91,157.43,151.49,136.72,135.55,129.97,128.89,127.80,126.01,118.39,100.03,61.72,34.49,34.32,30.12,23.84,13.75.HRMS:calcd.for C 29 H 37 NO 3 [M+Na]+470.2665；found470.2667.
Example 5
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (4-methoxyphenyl) acrylate in 73% yield.
1 H NMR(400MHz,CDCl 3 )δ7.41(d,J＝8.4Hz,1H),7.26(s,1H),7.13(d,J＝8.7Hz,1H),6.97–6.85(m,3H),5.69(s,1H),4.14(dq,J＝24.2,7.1Hz,2H),3.86(d,J＝4.1Hz,3H),1.39(d,J＝6.7Hz,18H),1.22–1.08(m,3H). 13 C NMR(101MHz,CDCl 3 )δ170.79,164.01,161.67,157.51,135.57,133.09,132.10,129.06,127.93,118.65,113.37,99.07,61.74,55.37,34.48,30.16,13.99.HRMS:calcd.for C 27 H 33 NO 4 [M+Na]+458.2301；found 458.2299.
Example 6
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (2-methoxyphenyl) acrylate in 68% yield.
1 H NMR(400MHz,CDCl 3 )δ7.38(ddd,J＝8.5,6.9,2.5Hz,1H),7.29(d,J＝22.9Hz,2H),7.01–6.90(m,3H),5.63(s,1H),4.14(dq,J＝14.3,7.1Hz,2H),3.75(d,J＝26.1Hz,3H),1.37(d,J＝9.5Hz,18H),1.16(dt,J＝12.8,7.2Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ166.31,163.14,157.03,156.44,135.49,131.01,130.51,129.33,128.59,128.02,127.13,120.37,110.80,102.39,61.52,55.62,34.50,30.13,13.93.HRMS:calcd.for C 27 H 33 NO 4 [M+Na]+458.2301；
found 458.2299.
Example 7
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (4-hydroxyphenyl) acrylate in 82% yield.
1 H NMR(400MHz,CDCl 3 )δ7.34–7.24(m,2H),7.07–7.03(m,1H),6.96(s,1H),6.83–6.72(m,2H),4.17(dq,J＝35.5,7.1Hz,2H),1.38(d,J＝7.5Hz,18H),1.18(dt,J＝50.8,7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ172.20,164.81,159.00,157.80,135.66,133.39,132.44,129.26,128.20,115.22,98.00,62.14,34.48,30.13,13.96.HRMS:calcd.for C 26 H 31 NO 4 [M+Na]+444.2145；found 444.2137.
Example 8
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (4- (dimethylamino) phenyl) acrylate in 81% yield.
1 H NMR(400MHz,CDCl 3 )δ7.41–7.25(m,2H),7.09–6.96(m,2H),6.68–6.57(m,2H),5.53(s,1H),4.22–4.02(m,2H),3.05(d,J＝4.7Hz,6H),1.40(d,J＝7.2Hz,18H),1.25(t,J＝7.1Hz,1H),1.06(t,J＝7.1Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ171.07,165.05,156.42,152.81,135.31,133.63,130.57,128.08,124.94,119.79,110.75,95.58,61.29,40.04,34.31,30.29,13.91.HRMS:calcd.for C 28 H 36 N 2 O 3 [M+Na]+471.2618；found 471.2625.
Example 9
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (4-fluorophenyl) acrylate in 77% yield.
1 H NMR(400MHz,CDCl 3 )δ7.48–7.42(m,1H),7.26(s,1H),7.20–7.05(m,3H),6.94(d,J＝1.1Hz,1H),5.73(s,1H),4.14(qt,J＝7.2,1.8Hz,2H),1.38(dd,J＝6.5,1.2Hz,18H),1.20–1.11(m,3H). 13 C NMR(101MHz,CDCl 3 )δ169.52,165.15,163.40,162.65,157.70,135.80,133.06,131.75,129.03,128.80,118.07,115.34,115.12,100.63,61.94,34.51,30.21,13.89.HRMS:calcd.for C 26 H 30 FNO 3 [M+Na]+446.2101；found 446.2100.
Example 10
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (2-fluorophenyl) acrylate in 79% yield.
1 H NMR(400MHz,CDCl 3 )δ7.43(tdd,J＝7.2,5.2,1.8Hz,1H),7.34–7.24(m,2H),7.19–6.99(m,3H),5.71(d,J＝1.4Hz,1H),4.18(q,J＝7.3Hz,2H),1.39(s,18H),1.20(t,J＝7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ163.53,162.60,160.54,157.55,135.81,131.04,128.17,123.85,117.72,115.50,102.83,61.97,34.53,30.08,13.91.HRMS:calcd.for C 26 H 30 FNO 3
[M+Na]+446.2101；found 446.2100.
Example 11
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (4-bromophenyl) acrylate in 77% yield.
1 H NMR(400MHz,CDCl 3 )δ7.59–7.48(m,2H),7.29(d,J＝25.9Hz,2H),7.08–6.90(m,2H),5.73(s,1H),4.15(q,J＝7.1Hz,2H),1.38(d,J＝6.8Hz,18H),1.16(dt,J＝14.6,7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ169.38,163.21,157.74,138.13,135.85,131.70,131.28,128.73,127.79,124.73,117.95,100.91,62.03,34.53,30.16,13.88.HRMS:calcd.for C 26 H 30 BrNO 3 [M+Na]+508.1282；found 508.1287.
Example 12
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (2-bromophenyl) acrylate in 58% yield.
1 H NMR(400MHz,CDCl 3 )δ7.65–7.56(m,1H),7.41–7.19(m,4H),7.11–7.06(m,1H),5.70(s,1H),4.16–4.04(m,2H),1.42(s,3H),1.39(s,15H),1.19–1.02(m,3H). 13 C NMR(101MHz,CDCl 3 )δ168.14,162.14,157.48,140.38,135.87,132.66,129.97,129.27,128.00,127.06,125.12,121.67,117.55,102.84,61.93,34.56,30.07,13.85.HRMS:calcd.for C 26 H 30 BrNO 3 [M+Na]+508.1282；found 508.1287.
Example 13
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (4-nitrophenyl) acrylate in 79% yield.
1 H NMR(400MHz,CDCl 3 )δ8.31–8.23(m,2H),7.39–7.23(m,4H),5.78(s,1H),4.15(q,J＝7.0Hz,2H),1.37(d,J＝5.3Hz,18H),1.20(t,J＝7.2Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ168.00,162.46,158.04,148.29,145.89,136.19,129.98,128.44,127.92,123.26,117.34,102.09,62.32,34.58,30.02,13.91.HRMS:calcd.for C 26 H 30 N 2 O 5 [M+Na]+473.2046；found 473.2042.
Example 14
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (2-nitrophenyl) acrylate in 76% yield.
1 H NMR(400MHz,CDCl 3 )δ7.43(tdd,J＝7.9,5.5,1.5Hz,1H),7.33(d,J＝1.2Hz,2H),7.19–7.01(m,3H),5.71(d,J＝1.4Hz,1H),4.18(q,J＝7.2Hz,2H),1.40–1.38(m,18H),1.20(t,J＝7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ186.43,163.46,159.86,156.27,151.68,148.87,148.36,135.45,133.15,131.88,131.72,131.04,130.97,130.89,129.83,128.98,128.83,128.68,123.86,123.83,115.95,115.73,35.26,33.76,30.78,29.78,28.05.HRMS:calcd.for C 26 H 30 N 2 O 5 [M+Na]+473.2046；found 473.2042.
Example 15
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (2, 6-dichlorophenyl) acrylate in 78% yield.
1 H NMR(400MHz,CDCl 3 )δ7.72–7.67(m,2H),7.31(s,1H),7.24(s,2H),5.78(s,1H),4.14(q,J＝7.1Hz,2H),1.38(s,18H),1.18(t,J＝7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ168.31,162.56,157.97,144.03,136.12,131.76,129.77,128.51,128.04,118.34,113.33,101.86,62.25,34.57,30.03,13.88.HRMS:calcd.for C 26 H 29 Cl 2 NO 3 [M+Na]+496.1416；found 496.1418.
Example 16
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (3, 4, 5-trimethoxyphenyl) acrylate in 87% yield.
1 H NMR(400MHz,CDCl 3 )δ7.33–6.96(m,2H),6.60(d,J＝31.4Hz,1H),6.39(s,1H),5.72(s,1H),4.12(p,J＝7.4Hz,2H),3.94–3.72(m,9H),1.38(d,J＝7.1Hz,18H),1.17–1.04(m,3H). 13 C NMR(101MHz,CDCl 3 )δ169.59,163.95,157.70,152.75,139.90,135.66,134.49,129.00,128.13,118.22,107.53,100.08,61.87,61.09,56.32,34.53,30.15,13.94.HRMS:calcd.for C 29 H 37 NO 6 [M+Na]+518.2513；found 518.2507.
Example 17
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (naphthalen-2-yl) acrylate in 89% yield.
1 H NMR(400MHz,CDCl 3 )δ7.90–7.80(m,3H),7.61–7.49(m,2H),7.44–7.36(m,1H),7.34–7.23(m,2H),7.18–7.00(m,1H),5.72(d,J＝1.6Hz,1H),4.13(dq,J＝32.7,7.1Hz,2H),1.38(d,J＝2.7Hz,18H),1.16(t,J＝7.1Hz,1H),1.04(t,J＝7.1Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ170.48,163.67,157.59,136.68,135.75,133.97,132.59,129.64,129.17,128.89,128.64,127.87,127.60,126.96,126.68,126.13,118.26,100.98,61.87,34.52,30.14,13.80.HRMS:calcd.for C 30 H 33 NO 3 [M+Na]+478.2352；found 478.2345.
Example 18
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give ethyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (thiophen-2-yl) acrylate in 81% yield.
1 H NMR(400MHz,CDCl 3 )δ7.81(dd,J＝3.9,1.2Hz,1H),7.64(ddd,J＝17.9,5.1,1.2Hz,1H),7.22–7.14(m,1H),7.06(s,2H),5.57(s,1H),4.13(dq,J＝76.5,7.1Hz,2H),1.41(d,J＝3.2Hz,18H),1.27–1.22(m,1H),1.03(t,J＝7.1Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ163.83,160.49,156.42,141.42,135.48,134.43,133.70,129.86,128.24,127.20,118.30,98.04,61.80,34.36,30.24,13.77.HRMS:calcd.for C 24 H 29 NO 3 S[M+Na]+434.1760；found 434.1759.
Example 19
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give tert-butyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3-phenylacrylate in 79% yield.
1 H NMR(400MHz,CDCl 3 )δ7.48–7.41(m,1H),7.41–7.34(m,2H),7.25(d,J＝5.0Hz,2H),7.20–6.91(m,2H),5.65(s,1H),1.38(s,20H),1.30(s,7H). 13 C NMR(101MHz,CDCl 3 )δ168.60,162.70,157.19,139.68,135.54,130.63,129.60,128.60,127.96,127.42,118.31,102.84,82.86,34.49,30.11,27.56.HRMS:calcd.for C 28 H 25 NO 3 [M+Na]+456.2509；found 456.2512.
Example 20
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give tert-butyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (m-tolyl) acrylate in 75% yield.
1 H NMR(400MHz,CDCl 3 )δ7.25(d,J＝5.3Hz,4H),7.02–6.92(m,2H),5.65(s,1H),2.36(d,J＝7.3Hz,3H),1.39(d,J＝2.2Hz,20H),1.31(s,7H). 13 C NMR(101MHz,CDCl 3 )δ168.72,162.88,157.16,139.56,137.52,135.50,130.66,130.19,128.60,127.90,127.41,126.84,118.36,102.70,82.75,34.50,30.15,27.55,21.30.HRMS:calcd.for C 29 H 37 NO 3 [M+Na]+
470.2665；found 470.2668.
Example 21
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give tert-butyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (2-bromophenyl) acrylate in 77% yield.
1 H NMR(400MHz,CDCl 3 )δ7.69–7.56(m,1H),7.39–7.22(m,4H),7.15–7.08(m,1H),5.47(d,J＝144.9Hz,1H),1.44–1.33(m,18H),1.29–1.20(m,9H). 13 C NMR(101MHz,CDCl 3 )δ165.92,161.49,157.13,140.73,135.76,132.70,129.59,127.76,125.32,117.68,105.25,84.02,82.95,49.68,44.02,34.54,30.09,27.55.HRMS:calcd.for C 28 H 34 BrNO 3 [M+Na]+
536.1594；found 536.1598.
Example 22
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give tert-butyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (naphthalen-2-yl) acrylate in 73% yield.
1 H NMR(400MHz,CDCl 3 )δ7.93–7.75(m,3H),7.47(td,J＝17.5,8.5Hz,2H),7.21(dd,J＝38.0,2.2Hz,2H),5.19(d,J＝2.0Hz,1H),4.75(ddd,J＝12.2,8.9,2.1Hz,1H),4.22(dt,J＝9.1,2.9Hz,1H),1.43(dd,J＝7.6,2.0Hz,18H),1.23(dd,J＝6.4,1.8Hz,9H). 13 C NMR(101MHz,CDCl 3 )δ164.18,153.22,137.19,136.12,133.38,132.70,129.80,129.04,128.64,128.05,127.65,126.79,126.32,126.10,124.77,116.57,83.90,51.47,45.01,34.42,30.24,27.47.HRMS:calcd.for C 32 H 37 NO 3 [M+Na]+506.2665；found 506.2663.
Example 23
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give tert-butyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (3, 4, 5-trimethoxyphenyl) acrylate in 76% yield.
1 H NMR(400MHz,CDCl 3 )δ7.25(s,1H),7.13(s,1H),6.67(s,1H),6.58(s,1H),5.19(d,J＝5.1Hz,1H),4.45(dd,J＝14.0,8.5Hz,1H),4.05–3.96(m,1H),3.85(d,J＝7.6Hz,6H),3.81(d,J＝3.7Hz,3H),1.42(d,J＝5.6Hz,18H),1.23(d,J＝4.9Hz,9H). 13 C NMR(101MHz,CDCl 3 )δ164.06,153.21,137.31,136.07,135.52,128.76,124.63,116.59,105.34,83.85,60.88,56.10,53.47,52.07,45.97,34.43,30.23,27.43.HRMS:calcd.for C 31 H 41 NO 6 [M+Na]+546.2826；found 546.2827.
Example 24
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give methyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3-phenylacrylate in 84% yield.
1 H NMR(400MHz,CDCl 3 )δ7.52–7.25(m,5H),7.22–6.93(m,2H),5.67(d,J＝38.6Hz,1H),3.72(d,J＝22.2Hz,3H),1.38(d,J＝6.3Hz,18H). 13 C NMR(101MHz,CDCl 3 )δ171.39,163.83,157.65,139.15,135.68,130.78,129.54,128.88,128.33,128.01,118.26,99.86,52.66,34.51,30.10.HRMS:calcd.for C 25 H 29 NO 3 [M+Na]+414.2039；found 414.2039.
Example 25
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give methyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (p-tolyl) acrylate in 79% yield.
1 H NMR(400MHz,CDCl 3 )δ7.49–7.25(m,3H),7.21–6.81(m,3H),5.47–5.26(m,1H),3.11(hept,J＝6.9Hz,2H),1.44(s,1H),1.36–1.14(m,21H). 13 C NMR(101MHz,CDCl 3 )δ
168.67,162.64,153.47,139.49,133.63,131.18,130.28,129.71,127.98,127.08,118.22,103.04,82.97,27.57,27.15,22.53.HRMS:calcd.for C 26 H 31 NO 3 [M+Na]+428.2196；found 428.2194.
Example 26
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give methyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (naphthalen-2-yl) acrylate in 76% yield.
1 H NMR(400MHz,CDCl 3 )δ7.91–7.79(m,3H),7.69–7.47(m,3H),7.34–7.00(m,3H),5.72(s,1H),3.72(d,J＝41.2Hz,3H),1.37(d,J＝3.5Hz,18H). 13 C NMR(101MHz,CDCl 3 )δ171.34,163.95,157.71,136.51,135.77,134.02,132.59,131.52,129.75,128.97,128.72,128.26,127.89,127.60,126.94,126.65,118.33,100.19,52.71,34.52,30.12.HRMS:calcd.for C 29 H 31 NO 3 [M+Na]+464.2196；found 464.2197.
Example 27
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give methyl 2-cyano-3- (3, 5-di-tert-butyl-4-hydroxyphenyl) -3- (4-bromophenyl) acrylate in 81% yield.
1 H NMR(400MHz,CDCl 3 )δ7.60–7.50(m,2H),7.33–7.21(m,2H),7.10–6.91(m,2H),5.74(s,1H),3.74(d,J＝8.3Hz,3H),1.38(d,J＝7.2Hz,18H). 13 C NMR(101MHz,CDCl 3 )δ170.09,163.53,157.84,137.93,135.90,131.70,131.31,128.78,128.09,124.87,117.98,100.22,52.77,34.53,30.09.HRMS:calcd.for C 25 H 28 BrNO 3 [M+Na]+494.1125；found 494.1117.
Example 28
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc followed by extraction with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give 2-cyano-3- (4-hydroxy-3, 5-diisopropylphenyl) -3-phenylacrylate in 74% yield.
1 H NMR(400MHz,CDCl 3 )δ7.51–7.34(m,3H),7.22–7.09(m,3H),5.60–5.47(m,1H),4.15(dq,J＝17.9,7.1Hz,2H),3.12(hept,J＝6.8Hz,2H),1.18(t,J＝6.8Hz,12H),1.12(t,J＝7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ170.61,163.57,153.85,139.19,133.77,130.31,129.67,127.99,127.28,118.08,100.79,61.91,27.13,22.55,13.80.HRMS:calcd.for C 24 H 27 NO 3 [M+Na]+400.1883；found 400.1886.
Example 29
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc and then extracted with EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give tert-butyl 2-cyano-3- (4-hydroxy-3, 5-diisopropylphenyl) -3-phenylacrylate in 69% yield.
1 H NMR(400MHz,CDCl 3 )δ7.28–7.16(m,4H),7.07(t,J＝6.8Hz,2H),5.69(s,1H),2.41(s,3H),1.40(d,J＝4.9Hz,21H). 13 C NMR(101MHz,CDCl 3 )δ171.80,164.07,157.59,140.86,135.59,129.90,129.37,128.75,127.63,124.44,118.49,99.25,52.63,34.49,30.13,21.61.HRMS:calcd.for C 26 H 31 NO 3 [M+Na]+428.2196；found 428.2188.
Example 30
In a dry 25ml flask were successively added p-QM (0.5 mmol), cyanoacetate (0.5 mmol), elemental sulfur (S 8 ) (0.125 mmol), DBU (0.5 mmol) and DMSO (1 ml), the mixture was stirred at 100deg.C until the reaction was complete, etOAc (5 ml) and saturated sodium bicarbonate (5 ml) were added, stirred, split into two layers, extracted with EtOAc followed by EtOAc (3X 15 ml) and the crude product was separated by column chromatography to give methyl 2-cyano-3- (4-hydroxy-3, 5-diisopropylphenyl) -3-phenylacrylate in 72% yield.
1 H NMR(400MHz,CDCl 3 )δ7.52–7.33(m,3H),7.20–7.12(m,3H),7.03–6.82(m,1H),5.39(s,1H),3.77–3.64(m,3H),3.11(hept,J＝6.8Hz,2H),1.19(t,J＝7.0Hz,12H). 13 C NMR(101MHz,CDCl 3 )δ171.22,163.80,153.82,138.98,133.68,130.41,129.67,128.01,127.35,118.13,100.20,52.69,27.17,22.53.HRMS:calcd.for C 23 H 25 NO 3 [M+Na]+386.1726；found386.1725.
Applicant states that during the description of the above specification:
the terms "this embodiment," "an embodiment of the application," "as shown in … …," "further improved embodiments," and the like, mean that a particular feature, structure, material, or characteristic described in the embodiment or example is included in at least one embodiment or example of the application; in this specification, a schematic representation of the above terms is not necessarily directed to the same embodiment or example, and the particular features, structures, materials, or characteristics described, etc. may be combined or combined in any suitable manner in any one or more embodiments or examples; furthermore, various embodiments or examples, as well as features of various embodiments or examples, described in this specification may be combined or combined by one of ordinary skill in the art without undue experimentation.
Finally, it should be noted that:
the above embodiments are only for illustrating the technical solution of the present application, and are not limiting thereof;
although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art will appreciate that modifications may be made to the technical solutions described in the foregoing embodiments, or equivalents may be substituted for some or all of the technical features thereof, without departing from the spirit of the technical solutions of the embodiments of the present application, and that insubstantial improvements and modifications or substitutions by one skilled in the art from the disclosure herein are within the scope of the application as claimed.
Claims (10)
1. A novel method for synthesizing cyanoacrylate, comprising the steps of:
s1, adding a p-methylene quinone compound, cyanoacetate and elemental sulfur (S) 8 ) Stirring the mixture at a high temperature;
s2, after the reaction is finished, adding saturated sodium bicarbonate and ethyl acetate to dilute the mixture, stirring, extracting, separating and purifying to obtain the cyanoacrylate compound.
2. The novel process for the synthesis of cyanoacrylate according to claim 1, wherein in step S1, the preparation method of the p-methylenequinone compound comprises: 2, 6-di-tert-butylphenol/2, 6-diisopropylphenol, benzaldehyde with different substituents, toluene, piperidine and acetic anhydride are mixed and reacted in a reflux system.
3. A novel process for the synthesis of cyanoacrylates according to claim 2 wherein,
the chemical formula of the p-methylene quinone compound is as follows:
wherein R is 1 Including t-butyl, isopropyl; r is R 2 Electron withdrawing and donating groups including methyl, methoxy, isopropyl, N-dimethyl, nitro, cyano, fluoro, bromo, and di-and tri-substituted (chloro), and heterocycles of pyridine, thiophene, naphthalene;
and, the chemical reaction formula of step S1 is:
wherein R is 1 Including t-butyl, isopropyl; r is R 2 Electron withdrawing and donating groups including methyl, methoxy, isopropyl, N-dimethyl, nitro, cyano, fluoro, bromo, and di-and tri-substituted (chloro), and heterocycles of pyridine, thiophene, naphthalene; r is R 3 Including methyl, ethyl, t-butyl.
4. A novel method for synthesizing cyanoacrylate according to claim 1 wherein the organic solvent in step S1 comprises N, N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO), toluene, 1, 4-dioxane.
5. A novel process for the synthesis of cyanoacrylates according to claim 1 characterised in that in step S1 the base comprises potassium carbonate, triethylamine, potassium hydroxide, 1, 4-diazabicyclo [2.2.2] octane (DABCO), 1, 8-diazabicyclo undec-7-ene (DBU), sodium bicarbonate, potassium acetate.
6. The novel process for the synthesis of cyanoacrylate according to claim 1 wherein in step S1 the molar ratio of the p-methylenequinone compound, the cyanoacetate, elemental sulphur (S8) and the base is (1-2): (1-2): (0.25-0.5): (1-2).
7. The novel process for the synthesis of cyanoacrylate according to claim 1 wherein in step S1 the stirring is carried out at a temperature ranging from 90 to 120 ℃ for a period ranging from 6 to 10 hours.
8. A novel process for the synthesis of cyanoacrylates according to claim 1 wherein, in step S2, the extraction process comprises:
r1, extracted with a low concentration of EtOAc,
r2, extracted with high concentration EtOAc;
r3, washing an organic phase obtained by extracting and separating the liquid by using saturated sodium bicarbonate, and washing a water phase by using ethyl acetate;
the organic phase R4 was dried over anhydrous sodium sulfate and concentrated.
9. A novel process for the synthesis of cyanoacrylate according to claim 8 wherein the concentration of high concentration EtOAc is 3 times that of low concentration EtOAc.
10. The novel process for the synthesis of cyanoacrylate according to claim 1, wherein in step S2, the separation and purification are carried out by column chromatography, and the eluent used is a mixture of petroleum ether and ethyl acetate.
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