CN105753715A - Methylation method for amine - Google Patents
Methylation method for amine Download PDFInfo
- Publication number
- CN105753715A CN105753715A CN201610207593.8A CN201610207593A CN105753715A CN 105753715 A CN105753715 A CN 105753715A CN 201610207593 A CN201610207593 A CN 201610207593A CN 105753715 A CN105753715 A CN 105753715A
- Authority
- CN
- China
- Prior art keywords
- amine
- carbonate
- methylation method
- quadrosilan
- methylphenylamine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000011987 methylation Effects 0.000 title claims abstract description 21
- 238000007069 methylation reaction Methods 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims abstract description 20
- 150000001412 amines Chemical class 0.000 title claims abstract description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 63
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 38
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 32
- 239000003054 catalyst Substances 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 14
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 14
- 150000003141 primary amines Chemical class 0.000 claims abstract description 11
- 150000003335 secondary amines Chemical class 0.000 claims abstract description 11
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 9
- ZTQZMPQJXABFNC-UHFFFAOYSA-N 2,2,4,6,6,8-hexamethyl-4,8-diphenyl-1,3,5,7,2,4,6,8-tetraoxatetrasilocane Chemical compound O1[Si](C)(C)O[Si](C)(C=2C=CC=CC=2)O[Si](C)(C)O[Si]1(C)C1=CC=CC=C1 ZTQZMPQJXABFNC-UHFFFAOYSA-N 0.000 claims description 22
- 229960001328 quadrosilan Drugs 0.000 claims description 22
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 14
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 5
- 229960003805 amantadine Drugs 0.000 claims description 5
- RGQCAJMEHUBUKW-UHFFFAOYSA-N n-fluoro-n-methylaniline Chemical compound CN(F)C1=CC=CC=C1 RGQCAJMEHUBUKW-UHFFFAOYSA-N 0.000 claims description 5
- XWEDAOHUHOHFPJ-UHFFFAOYSA-N n-bromo-n-methylaniline Chemical compound CN(Br)C1=CC=CC=C1 XWEDAOHUHOHFPJ-UHFFFAOYSA-N 0.000 claims description 4
- TXTHKGMZDDTZFD-UHFFFAOYSA-N n-cyclohexylaniline Chemical compound C1CCCCC1NC1=CC=CC=C1 TXTHKGMZDDTZFD-UHFFFAOYSA-N 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- WPFGFHJALYCVMO-UHFFFAOYSA-L rubidium carbonate Chemical compound [Rb+].[Rb+].[O-]C([O-])=O WPFGFHJALYCVMO-UHFFFAOYSA-L 0.000 claims description 4
- 229910000026 rubidium carbonate Inorganic materials 0.000 claims description 4
- LNVWRBNPXCUYJI-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazol-4-amine Chemical compound CC1=NNC(C)=C1N LNVWRBNPXCUYJI-UHFFFAOYSA-N 0.000 claims 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims 1
- 231100000419 toxicity Toxicity 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 abstract 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 9
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 8
- 230000008014 freezing Effects 0.000 description 8
- 238000007710 freezing Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000005311 nuclear magnetism Effects 0.000 description 8
- 238000005086 pumping Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 4
- 230000001035 methylating effect Effects 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- SDIXRDNYIMOKSG-UHFFFAOYSA-L disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 description 2
- FBGJJTQNZVNEQU-UHFFFAOYSA-N n,3-dimethylaniline Chemical compound CNC1=CC=CC(C)=C1 FBGJJTQNZVNEQU-UHFFFAOYSA-N 0.000 description 2
- LXZGVFCKZRHKMU-UHFFFAOYSA-N n-benzyl-n-methylaniline Chemical compound C=1C=CC=CC=1N(C)CC1=CC=CC=C1 LXZGVFCKZRHKMU-UHFFFAOYSA-N 0.000 description 2
- HRBASXKYUKFHKC-UHFFFAOYSA-N n-cyclohexyl-n-methylaniline Chemical compound C=1C=CC=CC=1N(C)C1CCCCC1 HRBASXKYUKFHKC-UHFFFAOYSA-N 0.000 description 2
- 229960000888 rimantadine Drugs 0.000 description 2
- AXVOAMVQOCBPQT-UHFFFAOYSA-N triphos Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 AXVOAMVQOCBPQT-UHFFFAOYSA-N 0.000 description 2
- LFKXWKGYHQXRQA-FDGPNNRMSA-N (z)-4-hydroxypent-3-en-2-one;iron Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LFKXWKGYHQXRQA-FDGPNNRMSA-N 0.000 description 1
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 1
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical group C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 238000006824 Eschweiler-Clarke methylation reaction Methods 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a methylation method for amine. The methylation method is characterized by comprising the following steps: taking carbonate as a catalyst, taking carbon dioxide as a C1 source, taking diphenylsilane as a reducing agent, and reacting primary amine or secondary amine in an acetonitrile solvent, thereby obtaining a corresponding methylation product. The invention develops a new methylation method for amine, wherein the used raw materials are low in cost and low in toxicity, the reaction operation is simple, and the yield is high.
Description
Technical field
The present invention relates to the methylation method of a kind of amine.
Background technology
Methyl substituted amine is widely present in natural product, and has important application in big chemical industry, fine chemistry industry, medicine and dyestuff etc..And industrial traditional methylating is to be reacted by Eschweiler-ClarkeMethylation, this reaction is with the poisonous formaldehyde source as C1, and carboxylic acid is as reducing agent.In laboratory, conventional methylating reagent is highly toxic iodomethane, dimethyl sulfate, methyl tosylate, Azimethylene. etc..In recent years, scientists is found that a kind of new methylation method: utilize nontoxic, and cheap carbon dioxide is as the C1 source in the methylating of amine, and hydrogen or silane or borine are as reducing agent.Wherein, the most prominent with the work of Cantat, Beller, Klankermayer group.2013, Cantat group developed an IPrZnCl2Catalyst.In THF, under the effect of this catalyst, methylphenylamine, phenylsilane, and 1barCO2Within 20 hours, obtaining DMA 100 DEG C of reactions, productivity has reached 95%, and TON is 48, TOF is 2.4.Coexisting 2013, Beller group has developed the catalyst system and catalyzing (RuCl of a ruthenium2(dmso)4, BuPAd2), in toluene solvant, under the effect of this catalyst system and catalyzing, methylphenylamine, phenylsilane, and 30barCO2Within 16 hours, obtaining DMA 100 DEG C of reactions, productivity reaches 98%, and TON is 49, TOF is 3.1.Klankermayer group was also found that a catalyst in 2013, (Ru (triphos) (tmm)), in THF, under this catalyst action, and methylphenylamine, 60barH2CO with 20bar2Within 10 hours, obtaining DMA 150 DEG C of reactions, productivity reaches 99%, and it is 4.0 that TON reaches 40, TOF.In the same year, Beller group has developed the catalyst system and catalyzing (Ru (acac) of a ruthenium3, triphos).In THF, under catalyst system and catalyzing effect, aniline, the H of 60bar2And 20barCO2Within 16 hours, obtaining corresponding DMA 140 DEG C of reactions, productivity has reached 96%, and TON has reached 96, TOF and reached 6.0.In 2014, Cantat group developed a ferrum catalyst system and catalyzing (Fe (acac)2, PP3).In THF, under this catalyst system and catalyzing effect, methylphenylamine, the CO of phenylsilane and 1bar2Within 18 hours, obtain the DMA of correspondence 100 DEG C of reactions, productivity reaches 55%, and TON is 5.5, TOF is 0.31.2014, Cantat there have been developed first non-metallic catalyst, VBMe.In THF, under this catalyst action, with 9-BBN as reducing agent, methylphenylamine and 1barCO2Within 0.17 hour, obtaining corresponding methylate 90 DEG C of reactions, productivity has reached 98%, and TON reaches 490, TOF and reached 2934.By observing it is seen that, the synthesis of the catalyst in these catalyst system and catalyzings is typically complex, and price comparison is expensive.Therefore find low toxicity, methylation method cheap, efficient still seems very necessary.
Summary of the invention
The purpose of the present invention is to propose to a kind of methylation catalytic method of new amine, high to solve methylating reagent toxicity used in the methylation method of existing amine, or the shortcoming such as expensive catalyst, thus the preparation for N-methyl amine provides another kind of approach cheap, efficient.
In order to achieve the above object, the invention provides the methylation method of a kind of amine, it is characterised in that, including: with carbonate for catalyst, carbon dioxide is as C1 source, and quadrosilan is as reducing agent, primary amine or secondary amine are reacted in acetonitrile solvent, obtains corresponding methylate.
Preferably, described carbonate is cesium carbonate, rubidium carbonate or potassium carbonate.
Preferably, described primary amine or secondary amine at least one in the fluoro-methylphenylamine of 4-, Phenhenzamine, amantadine, N-cyclohexyl aniline, the bromo-methylphenylamine of 4-, N-methyl meta-aminotoluene and methylphenylamine.
Preferably, the consumption of described carbonate is the 0.01-30mol% of the consumption of primary amine or secondary amine.
Preferably, the mol ratio of described quadrosilan and primary amine or secondary amine is 1-6: 1.
Preferably, described reaction temperature is 0 DEG C-100 DEG C, and the response time is 12h-72h.
Preferably, before described reaction, first by primary amine or secondary amine in glove box, quadrosilan, carbonate and acetonitrile join N2In schlenk pipe under protection, again through biexhaust pipe by N therein2It is replaced as CO2。
Preferably, the pressure of described carbon dioxide is 0.1-2bar.
Compared with prior art, the invention has the beneficial effects as follows:
The present invention opens the methylation method of a kind of new amine, and raw materials used cost is low, and toxicity is little, and operation is simple, productivity is high.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is expanded on further.Should be understood that these embodiments are merely to illustrate the present invention rather than restriction the scope of the present invention.In addition, it is to be understood that after having read the content that the present invention lectures, the present invention can be made various changes or modifications by those skilled in the art, and these equivalent form of values fall within the application appended claims limited range equally.
Embodiment 1
The preparation of the fluoro-DMA of 4-:
1) by fluoro-for 0.25mmol4-methylphenylamine in glove box; 6equiv (1.5mmol) quadrosilan; 10mol% (with the fluoro-methylphenylamine of 4-for benchmark) cesium carbonate, 1.6ml acetonitrile solvent joins in the schlenk pipe under 50mlN2 protection.
2) by biexhaust pipe under freezing vacuum pumping by the N in schlenk pipe2It is replaced as CO2, CO2Pressure be 1bar.
3) with described cesium carbonate for catalyst, described carbon dioxide is as C1 source, and the described fluoro-methylphenylamine of 4-, as reducing agent, is reacted 72 hours in 80 DEG C by described quadrosilan in acetonitrile solvent.
4), after reaction terminates, adding 0.2mmol ferrocene in schlenk pipe is mark in nuclear-magnetism.
5) by Bruker nmr analysis, the nuclear magnetic spectrogram of products therefrom and document (Z.Yang, B.Yu, H.Zhang, Y.Zhao, G.Ji, Z.Ma, X.Gao, Z.Liu, GreenChem.2015,17,4189-4193.) in the corresponding pure material spectrogram reported for work consistent, the productivity > 95% of the fluoro-DMA of 4-in the present embodiment.
Embodiment 2
The preparation of N-methyl-N-benzyl aniline:
1) by 0.25mmolN-benzylaniline, 6equiv (1.5mmol) quadrosilan in glove box, 10mol% (with Phenhenzamine for benchmark) cesium carbonate, 1.6ml acetonitrile solvent joins 50mlN2In schlenk pipe under protection.
2) by biexhaust pipe under freezing vacuum pumping by the N in schlenk pipe2It is replaced as CO2, CO2Pressure be 1bar.
3) with described cesium carbonate for catalyst, described carbon dioxide is as C1 source, and the described fluoro-methylphenylamine of 4-, as reducing agent, is reacted 72 hours in 80 DEG C by described quadrosilan in acetonitrile solvent.
4), after reaction terminates, adding 0.2mmol ferrocene in schlenk pipe is mark in nuclear-magnetism.
5) by Bruker nmr analysis, the nuclear magnetic spectrogram of products therefrom and document (M.-C.Fu, R.Shang, W.-M.Cheng, Y.Fu, AngewandteChemieInternationalEdition2015,54,9042-9046.) in the corresponding pure material spectrogram reported for work consistent, the productivity > 95% of N-methyl N-benzylaniline in the present embodiment.
Embodiment 3
The preparation of N-rimantadine:
1) by 0.25mmol amantadine, 6equiv (1.5mmol) quadrosilan in glove box, 10mol% (with amantadine for benchmark) cesium carbonate, 1.6ml acetonitrile solvent joins 50mlN2In schlenk pipe under protection.
2) by biexhaust pipe under freezing vacuum pumping by the N in schlenk pipe2It is replaced as CO2, CO2Pressure be 1bar.
3) with described cesium carbonate for catalyst, described carbon dioxide is as C1 source, and described amantadine, as reducing agent, is reacted 72 hours in 80 DEG C by described quadrosilan in acetonitrile solvent.
4), after reaction terminates, adding 0.2mmol ferrocene in schlenk pipe is mark in nuclear-magnetism.
5) by Bruker nmr analysis, the nuclear magnetic spectrogram of products therefrom and document (P.Besenius, P.A.G.Cormack, R.F.Ludlow, S.Otto, D.C.Sherrington, Chem.Commun.2008,2809.) in the corresponding pure material spectrogram reported for work consistent, the productivity > 95% of N-rimantadine in the present embodiment.
Embodiment 4
The preparation of N-methyl-N-cyclohexyl aniline:
1) by 0.25mmolN-cyclohexyl aniline, 6equiv (1.5mmol) quadrosilan in glove box, 10mol% (with N-cyclohexyl aniline for benchmark) cesium carbonate, 1.6ml acetonitrile solvent joins 50mlN2In schlenk pipe under protection.
2) by biexhaust pipe under freezing vacuum pumping by the N in schlenk pipe2It is replaced as CO2, CO2Pressure be 1bar.
3) with described cesium carbonate for catalyst, described carbon dioxide is as C1 source, and described N-cyclohexyl aniline, as reducing agent, is reacted 72 hours in 80 DEG C by described quadrosilan in acetonitrile solvent.
4), after reaction terminates, adding 0.2mmol ferrocene in schlenk pipe is mark in nuclear-magnetism.
5) by Bruker nmr analysis, the nuclear magnetic spectrogram of products therefrom and document (S.Sueki, Y.Kuninobu, Org.Lett.2013,15,1544-1547.) in the corresponding pure material spectrogram reported for work consistent, the productivity > 95% of N-methyl-N-cyclohexyl aniline in the present embodiment.
Embodiment 5
The preparation of the bromo-DMA of 4-:
1) by bromo-for 0.25mmol4-methylphenylamine, 6equiv (1.5mmol) quadrosilan in glove box, 5mol% (with the bromo-methylphenylamine of 4-for benchmark) cesium carbonate, 1.6ml acetonitrile solvent joins 50mlN2In schlenk pipe under protection.
2) by biexhaust pipe under freezing vacuum pumping by the N in schlenk pipe2It is replaced as CO2, CO2Pressure be 1bar.
3) with described cesium carbonate for catalyst, described carbon dioxide is as C1 source, and the described bromo-methylphenylamine of 4-, as reducing agent, is reacted 48 hours in 80 DEG C by described quadrosilan in acetonitrile solvent.
4), after reaction terminates, adding 0.2mmol ferrocene in schlenk pipe is mark in nuclear-magnetism.
5) by Bruker nmr analysis, the nuclear magnetic spectrogram of products therefrom and document (Z.Yang, B.Yu, H.Zhang, Y.Zhao, G.Ji, Z.Ma, X.Gao, Z.Liu, GreenChem.2015,17,4189-4193.) in the corresponding pure material spectrogram reported for work consistent, in the present embodiment, the productivity of the bromo-DMA of 4-is 91%.
Embodiment 6
The preparation of N, N-dimethyl meta-aminotoluene:
1) by 0.25mmolN-methyl-meta-aminotoluene, 6equiv (1.5mmol) quadrosilan in glove box, 10mol% (with N-methyl-meta-aminotoluene for benchmark) cesium carbonate, 1.6ml acetonitrile solvent joins 50mlN2In schlenk pipe under protection.
2) by biexhaust pipe under freezing vacuum pumping by the N in schlenk pipe2It is replaced as CO2, CO2Pressure be 1bar.
3) with described cesium carbonate for catalyst, described carbon dioxide is as C1 source, and described N-methyl-meta-aminotoluene, as reducing agent, is reacted 72 hours in 80 DEG C by described quadrosilan in acetonitrile solvent.
4), after reaction terminates, adding 0.2mmol ferrocene in schlenk pipe is mark in nuclear-magnetism.
5) by Bruker nmr analysis, the nuclear magnetic spectrogram of products therefrom and document (Z.Yang, B.Yu, H.Zhang, Y.Zhao, G.Ji, Z.Ma, X.Gao, Z.Liu, GreenChem.2015,17,4189-4193.) in the corresponding pure material spectrogram reported for work consistent, the productivity > 95% of N, N-dimethyl meta-aminotoluene in the present embodiment.
Embodiment 7
The preparation of DMA:
1) by 0.5mmolN-monomethylaniline., 3equiv (1.5mmol) quadrosilan in glove box, 5mol% (with methylphenylamine for benchmark) potassium carbonate, 1.6ml acetonitrile solvent joins 50mlN2In schlenk pipe under protection.
2) by biexhaust pipe under freezing vacuum pumping by the N in schlenk pipe2It is replaced as CO2, CO2Pressure be 1bar.
3) with described potassium carbonate for catalyst, described carbon dioxide is as C1 source, and described methylphenylamine, as reducing agent, is reacted 24 hours in 80 DEG C by described quadrosilan in acetonitrile solvent.
4), after reaction terminates, adding 0.2mmol ferrocene in schlenk pipe is mark in nuclear-magnetism.
5) by Bruker nmr analysis, the nuclear magnetic spectrogram of products therefrom and document (Z.Yang, B.Yu, H.Zhang, Y.Zhao, G.Ji, Z.Ma, X.Gao, Z.Liu, GreenChem.2015,17,4189-4193.) in the corresponding pure material spectrogram reported for work consistent, in the present embodiment, the productivity of DMA is 61%.
Embodiment 8
The preparation of DMA:
1) by 0.5mmolN-monomethylaniline., 3equiv (1.5mmol) quadrosilan in glove box, 5mol% (with methylphenylamine for benchmark) rubidium carbonate, 1.6ml acetonitrile solvent joins 50mlN2In schlenk pipe under protection.
2) by biexhaust pipe under freezing vacuum pumping by the N in schlenk pipe2It is replaced as CO2, CO2Pressure be 1bar.
3) with described rubidium carbonate for catalyst, described carbon dioxide is as C1 source, and described methylphenylamine, as reducing agent, is reacted 24 hours in 80 DEG C by described quadrosilan in acetonitrile solvent.
4), after reaction terminates, adding 0.2mmol ferrocene in schlenk pipe is mark in nuclear-magnetism.
5) by Bruker nmr analysis, the nuclear magnetic spectrogram of products therefrom and document (Z.Yang, B.Yu, H.Zhang, Y.Zhao, G.Ji, Z.Ma, X.Gao, Z.Liu, GreenChem.2015,17,4189-4193.) in the corresponding pure material spectrogram reported for work consistent, in the present embodiment, the productivity of DMA is 88%.
Claims (8)
1. the methylation method of an amine, it is characterised in that including: with carbonate for catalyst, carbon dioxide is as C1 source, and primary amine or secondary amine, as reducing agent, are reacted by quadrosilan in acetonitrile solvent, obtain corresponding methylate.
2. the methylation method of amine as claimed in claim 1, it is characterised in that described carbonate is cesium carbonate, rubidium carbonate or potassium carbonate.
3. the methylation method of amine as claimed in claim 1, it is characterised in that described primary amine or secondary amine at least one in the fluoro-methylphenylamine of 4-, Phenhenzamine, amantadine, N-cyclohexyl aniline, the bromo-methylphenylamine of 4-and tert-butylamine.
4. the methylation method of amine as claimed in claim 1, it is characterised in that the consumption of described carbonate is the 0.01-30mol% of the consumption of primary amine or secondary amine.
5. the methylation method of amine as claimed in claim 1, it is characterised in that the mol ratio of described quadrosilan and primary amine or secondary amine is 1-6: 1.
6. the methylation method of amine as claimed in claim 1, it is characterised in that described reaction temperature is 0 DEG C-100 DEG C, and the response time is 12h-72h.
7. the methylation method of amine as claimed in claim 1, it is characterised in that the pressure of described carbon dioxide is 0.1-2bar.
8. the methylation method of amine as claimed in claim 1, it is characterised in that before described reaction, first by primary amine or secondary amine in glove box, quadrosilan, carbonate and acetonitrile join N2In schlenk pipe under protection, again through biexhaust pipe by N therein2It is replaced as CO2。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610207593.8A CN105753715B (en) | 2016-04-05 | 2016-04-05 | A kind of methylation method of amine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610207593.8A CN105753715B (en) | 2016-04-05 | 2016-04-05 | A kind of methylation method of amine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105753715A true CN105753715A (en) | 2016-07-13 |
| CN105753715B CN105753715B (en) | 2018-02-13 |
Family
ID=56333509
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610207593.8A Expired - Fee Related CN105753715B (en) | 2016-04-05 | 2016-04-05 | A kind of methylation method of amine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105753715B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106748805A (en) * | 2016-11-25 | 2017-05-31 | 上海科技大学 | A kind of alkylation of amine |
| CN106986776A (en) * | 2017-03-29 | 2017-07-28 | 中国科学院化学研究所 | The method that aminated compounds N methylates is realized in a kind of utilization photocatalysis |
| CN107337606A (en) * | 2017-06-15 | 2017-11-10 | 上海科技大学 | A kind of methylation method of amine |
| CN112010767A (en) * | 2020-09-11 | 2020-12-01 | 南京晓庄学院 | Preparation method of methylamine |
-
2016
- 2016-04-05 CN CN201610207593.8A patent/CN105753715B/en not_active Expired - Fee Related
Non-Patent Citations (4)
| Title |
|---|
| CHI FANG ET AL.: "Selective Formylation and Methylation of Amines using Carbon Dioxide and Hydrosilane Catalyzed by Alkali-Metal Carbonates", 《ACS CATAL.》 * |
| OLIVIER JACQUET ET AL.: "CO2 as a C1-building block for the catalytic methylation of amines", 《CHEMICAL SCIENCE》 * |
| YUEHUI LI ET AL.: "A General Catalytic Methylation of Amines Using Carbon Dioxide", 《ANGEW. CHEM.》 * |
| 崔新江等: "二氧化碳催化加氢制N-甲基胺类化合物催化体系研究", 《第十四届全国青年催化学术会议会议论文集》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106748805A (en) * | 2016-11-25 | 2017-05-31 | 上海科技大学 | A kind of alkylation of amine |
| CN106748805B (en) * | 2016-11-25 | 2019-03-19 | 上海科技大学 | A kind of alkylation of amine |
| CN106986776A (en) * | 2017-03-29 | 2017-07-28 | 中国科学院化学研究所 | The method that aminated compounds N methylates is realized in a kind of utilization photocatalysis |
| CN106986776B (en) * | 2017-03-29 | 2019-08-16 | 中国科学院化学研究所 | A method of realizing that aminated compounds N- methylates using photocatalysis |
| CN107337606A (en) * | 2017-06-15 | 2017-11-10 | 上海科技大学 | A kind of methylation method of amine |
| CN107337606B (en) * | 2017-06-15 | 2019-09-17 | 上海科技大学 | A kind of methylation method of amine |
| CN112010767A (en) * | 2020-09-11 | 2020-12-01 | 南京晓庄学院 | Preparation method of methylamine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105753715B (en) | 2018-02-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Frogneux et al. | Iron-catalyzed hydrosilylation of CO 2: CO 2 conversion to formamides and methylamines | |
| Rodriguez et al. | Palladium-catalyzed N-(2-pyridyl) sulfonyl-directed C (sp 3)–H γ-arylation of amino acid derivatives | |
| Tu et al. | A highly efficient precatalyst for amination of aryl chlorides: synthesis, structure and application of a robust acenaphthoimidazolylidene palladium complex | |
| CN105753715A (en) | Methylation method for amine | |
| Dong et al. | Mannich reaction in water using acidic ionic liquid as recoverable and reusable catalyst | |
| Wu et al. | An efficient way for the N-formylation of amines by inorganic-ligand supported iron catalysis | |
| Mai et al. | n Bu 4 NI-catalyzed unexpected amide bond formation between aldehydes and aromatic tertiary amines | |
| Zhang et al. | Aryl-palladium-NHC complex: efficient phosphine-free catalyst precursors for the carbonylation of aryl iodides with amines or alkynes | |
| Kobayashi | The new world of organic reactions in water | |
| Jha et al. | Synthesis of glucose-tagged triazolium ionic liquids and their application as solvent and ligand for copper (I) catalyzed amination | |
| Basnet et al. | The copper-catalysed Suzuki–Miyaura coupling of alkylboron reagents: disproportionation of anionic (alkyl)(alkoxy) borates to anionic dialkylborates prior to transmetalation | |
| Wu et al. | Expeditious approach to α-amino phosphonates via three-component solvent-free reactions catalyzed by NBS or CBr 4 | |
| Fu et al. | Direct oxidative amidation of aldehydes with amines catalyzed by heteropolyanion-based ionic liquids under solvent-free conditions via a dual-catalysis process | |
| CN105152922A (en) | Method for synthesizing benzoic acid with thioxanthone catalyst under condition of illumination | |
| CN105061185A (en) | Method for catalytic synthesis of benzoic acid by use of anthraquinone under lighting condition | |
| Genre et al. | Additive-free selective methylation of secondary amines with formic acid over a Pd/In 2 O 3 catalyst | |
| CN101664699A (en) | Catalyzer used for preparing acidamide compound and application thereof | |
| CN102452901A (en) | Method for preparing phenol by performing direct hydroxylation on benzene | |
| Zheng et al. | A novel method to access chiral nonnatural 2, 4-disubstituted pyrrolidines from aldehydes and nitroolefins only with an α-substituent | |
| CN110294701A (en) | A kind of synthetic method of 5- N-methyl-2-2-pyrrolidone N or derivatives thereof | |
| CN106008265A (en) | Palladium-catalyzed benzyl quaternary ammonium salt C-N bond fission Suzuki coupling method | |
| de Jong et al. | One-pot, modular approach to functionalized ketones via nucleophilic addition/Buchwald–Hartwig amination strategy | |
| Fu et al. | Humic acid-catalyzed efficient synthesis of α-aminonitriles in water using potassium hexacyanoferrate (II) as a cyanide source | |
| CN104447391A (en) | Methylenebisamide derivative and preparation method thereof | |
| CN105601523A (en) | Method for synthesizing 2,5-dimethoxy-4-chloroaniline |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180213 |