CN105503791A - 2-hydroxymethyl-5-aminomethyl-furan compound synthesis method - Google Patents

2-hydroxymethyl-5-aminomethyl-furan compound synthesis method Download PDF

Info

Publication number
CN105503791A
CN105503791A CN201410484223.XA CN201410484223A CN105503791A CN 105503791 A CN105503791 A CN 105503791A CN 201410484223 A CN201410484223 A CN 201410484223A CN 105503791 A CN105503791 A CN 105503791A
Authority
CN
China
Prior art keywords
amine
methylol
furan compounds
methyl furan
synthesizing
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.)
Pending
Application number
CN201410484223.XA
Other languages
Chinese (zh)
Inventor
张宗超
许占威
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dalian Institute of Chemical Physics of CAS
Original Assignee
Dalian Institute of Chemical Physics of CAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Dalian Institute of Chemical Physics of CAS filed Critical Dalian Institute of Chemical Physics of CAS
Priority to CN201410484223.XA priority Critical patent/CN105503791A/en
Publication of CN105503791A publication Critical patent/CN105503791A/en
Pending legal-status Critical Current

Links

Landscapes

  • Furan Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention relates to a 2-hydroxymethyl-5-aminomethyl-furan compound synthesis method, and belongs to the field of chemical synthesis. The method comprises: weighing a divalent ruthenium coordination compound, an amine substrate and 5-hydroxymethyl furfural, dissolving in a solvent, and carrying out an amine reducing reaction for 4-36 h at a reaction temperature of 30-100 DEG C under a hydrogen pressure of 1.0-2.0 Mpa by adopting the 5-hydroxymethyl furfural as a raw material, adopting hydrogen as a reducing agent and adopting the divalent ruthenium coordination compound as a catalyst according to a molar ratio of the amine substrate to the divalent ruthenium coordination compound to the 5-hydroxymethyl furfural of 1.0-2.0:0.001-0.01:1 so as to synthesize the 2-hydroxymethyl-5-aminomethyl-furan compound. According to the present invention, the ruthenium coordination compound is adopted as the catalyst, the hydrogen is adopted as the reducing agent, the operation is simple, the raw material cost is low, and the reaction efficiency is high.

Description

A kind of method of synthesizing 2-methylol-5-amine methyl furan compounds
Technical field
The invention belongs to the field of chemical synthesis, be specifically related to a kind of method of synthesizing 2-methylol-5-amine methyl furan compounds.
Background technology
The exhaustion day by day of the growth consumed along with fossil resource and reserves, the exploitation of renewable resources receive much concern.Biomass are renewable resourcess that class reserves are large, distribution is wide, cost is low, are that raw material production chemical will alleviate the heavy dependence of social development to fossil resource (Chem.Rev.2007,107,2411 – 2502) to a certain extent with biomass.Lignocellulose is biomass main components, is made up of Mierocrystalline cellulose (35 ~ 50%), hemicellulose (20 ~ 35%) and xylogen (10 ~ 25%).Compared with the xylogen of complex structure, stable in properties, Mierocrystalline cellulose, hemicellulose are easy to be hydrolyzed and produce the carbohydrate that glucose is master.
5 hydroxymethyl furfural (5-HMF) is one of chemical received much concern in recent years, can obtain (Science2006,312,1933 – 1937 by glucose or fructose through dehydration reaction; Science2007,316,1597 – 1600).Take 5-HMF as platform chemicals, the multiple Chemicals (Chem.Rev.2011,111,397 – 417) having more added value can be prepared through reactions such as oxidation, reduction, condensations.
2-methylol-5-amine methyl furan compounds has biological activity usually, its research as drug molecule is subject to people's extensive concern always, as regulated (WOPat.2008145616), glycine antagonists (WOPat.2008065500), muscarine stimulant (J.Med.Chem.1994 as antihistamine (USPat.19814279911), L-glutamic acid, 37,4278 – 4287), Pyricularia oryzae inhibitor (Chinese pharmaceutical chemistry magazine, 3rd phase in 2007,129 – 134), calcium channel blocker etc. uses (USPat.19885017586).Therefore, 2-methylol-5-amine methyl furan compounds study on the synthesis significant (Fig. 9).
2-methylol-5-amine methyl furan compounds can be prepared by the Mannich reaction of furans, formaldehyde, amine (J.Chem.Soc.1958,4728 – 4731).The furfuran compound that Mannich reaction uses is transformed by Biomass-based chemicals 5-HMF or furfural (furfural) and obtains, and primary amine reaction activity is low simultaneously.And reductive amination process directly with Biomass-based chemicals 5-HMF for raw material, shorten synthetic route, compare with Mannich reaction, have more development prospect, meet Green Chemistry require (Figure 10).
The reductive amination process of secondary amine and 5-HMF and derivative thereof needs to use Na (OAc) 3bH (WOPat.2007142584; Bioorg.Med.Chem.2012,20,5893 – 5900) as reductive agent; Primary amine and 5-HMF and derivatives reaction thereof are realized (Eur.J.Med.Chem.2012,55,243 – 254) by two-step reaction: acid catalysis aldehyde, amine condensation Schiff's base; NaBH 4reduced Schiff base.The people such as Stevens (GreenChem.2010,12,1201 – 1206) report one pot of two-step approach, NaBH 4as reductive agent, the reductive amination process of 5-HMF and primary amine.This reaction is without the need to using catalyzer, and solvent is water and alcohol, but need microwave heating, arylamine reaction activity low, use excessive NaBH 4for the factors such as reductive agent limit the widespread use of the method.
Summary of the invention
The present invention seeks to for existing 2-methylol-5-amine methyl furan compounds synthetic method Problems existing, provide one with divalent ruthenium title complex for catalyzer, hydrogen is reductive agent, take 5-HMF as the novel method that initiator prepares 2-methylol-5-amine methyl furan compounds.
A kind of method of synthesizing 2-methylol-5-amine methyl furan compounds of the present invention, carry out according to following steps:
Take divalent ruthenium title complex, amine substrate, 5 hydroxymethyl furfural be dissolved in solvent, take 5 hydroxymethyl furfural as raw material, hydrogen is reductive agent, divalent ruthenium title complex is catalyzer, carry out reductive amination process, wherein the ratio of amine substrate, divalent ruthenium title complex, 5 hydroxymethyl furfural amount of substance is 1.0 ~ 2.0:0.001 ~ 0.01:1; Hydrogen pressure is 1.0 ~ 2.0Mpa; Temperature of reaction is 30 ~ 100 DEG C; Reaction times is: 4 ~ 36h; Synthesis 2-methylol-5-amine methyl furan compounds.
Described amine substrate is primary amine or secondary amine.
Described primary amine structural formula is:
Wherein R 1=ortho position, the substituting group of a position and contraposition, comprises H, F, Cl, Br, Me, OMe, OH or NH 2.
Described secondary amine structural formula is:
Wherein, R 2=ortho position, the substituting group of a position and contraposition, comprises H, F, Cl, Br, Me, OMe, OH or NH 2
R 3=Me, Et, n-Pr, i-Pr or n-Bu;
X=CH 2, O, NH or NR 3;
N＝0～10,m＝0～10。
Described divalent ruthenium complex structure formula is:
The structural formula of synthesized 2-methylol-5-amine methyl furan compounds is:
Wherein, R 1=ortho position, the substituting group of a position and contraposition, comprises H, F, Cl, Br, Me, OMe, OH or NH 2
R 2=Me, Et, n-Pr, i-Pr or n-Bu;
X=CH 2, O, NH or NR 3;
N＝0～10,m＝0～10。
Described solvent is methyl alcohol, ethanol, ethylene glycol, water, benzene, toluene, methylene dichloride, dimethyl sulfoxide (DMSO), DMF, ethyl acetate, tetrahydrofuran (THF), acetonitrile or chloroform.
Described 5 hydroxymethyl furfural concentration is 50 – 200gL -1.
Beneficial effect of the present invention is: ruthenium complexe is catalyzer, and hydrogen is reductive agent, and simple to operate, raw materials cost is low, and reaction efficiency is high.
Accompanying drawing explanation
Fig. 1 (5-((phenylamino) methyl) furan-2-yl) methanol's 1hNMR spectrogram
Fig. 2 (5-((phenylamino) methyl) furan-2-yl) methanol's 13cNMR spectrogram
Fig. 3 (5-(morpholinomethyl) furan-2-yl) methanol's 1hNMR spectrogram
Fig. 4 (5-(morpholinomethyl) furan-2-yl) methanol's 13cNMR spectrogram
Fig. 5 (5-(((4-methoxyphenyl) amino) methyl) furan-2-yl) methanol's 1hNMR spectrogram
Fig. 6 (5-(((4-methoxyphenyl) amino) methyl) furan-2-yl) methanol's 13cNMR spectrogram
Fig. 7 (5-((benzyl (methyl) amino) methyl) furan-2-yl) methanol's 1hNMR spectrogram
Fig. 8 (5-((benzyl (methyl) amino) methyl) furan-2-yl) methanol's 13cNMR spectrogram
Fig. 9 is the bioactive molecules structure of bibliographical information
Figure 10 is the synthesis of 2-methylol-5-amine methyl furan compounds
Embodiment
Below in conjunction with specific embodiment, the present invention is described further; but protection scope of the present invention is not by the restriction of embodiment; if the person skilled in the art in this field makes some nonessential improvement and adjustment according to the invention described above content to the present invention, still belong to protection scope of the present invention.Instrument used in following examples and model are: stirring heating reactor IKA model is RCTbasic, NMR testing tool is Bruker400MHz nuclear magnetic resonance spectrometer.
Embodiment 1
Aniline and 5-HMF react: weigh and get 63.0mg5-HMF, 51.2mg aniline, and 1.5mg catalyzer measures 1.0mL solvent.System hydrogen pressure is 1.5Mpa, and temperature is 60 DEG C, and the reaction times is 12h.Reaction terminates rear underpressure distillation and removes solvent, and adopt silicagel column separated product (5-((phenylamino) methyl) furan-2-yl) methanol, yield reaches as high as 93%.
(5-((phenylamino) methyl) furan-2-yl) methanol 1hNMR spectrogram 13cNMR spectrogram as depicted in figs. 1 and 2, as seen from the figure:
1HNMR(CDCl 3,400MHz)δ3.13(br,2H),4.30(s,2H),4.54(s,2H),6.18(d,J＝3.1Hz,1H),6.21(d,J＝3.1Hz,1H),6.67-6.78(m,3H),7.18-7.22(m,2H)； 13CNMR(CDCl 3,100MHz)δ41.6,57.4,107.8,108.6,113.3,118.2,129.3,147.6,152.9,153.5.
Embodiment 2
Morpholine and 5-HMF react: weigh and get 63.0mg5-HMF, 87.0mg morpholine, and 0.3mg catalyzer measures 1.0mL solvent.System hydrogen pressure is 2.0Mpa, and temperature is 30 DEG C, and the reaction times is 36h.Reaction terminates rear underpressure distillation and removes solvent, and adopt silicagel column separated product (5-(morpholinomethyl) furan-2-yl) methanol, yield reaches as high as 83%.
(5-(morpholinomethyl) furan-2-yl) methanol 1hNMR spectrogram 13cNMR spectrogram as shown in Figure 3 and Figure 4, as seen from the figure:
1HNMR(CDCl 3,400MHz)δ2.47-2.48(m,4H),2.65(br,1H),3.51(s,2H),3.70-3.72(m,4H),4.57(s,2H),6.17(d,J＝3.0Hz,1H),6.21(d,J＝3.0Hz,1H)； 13CNMR(CDCl 3,100MHz)δ53.3,55.4,57.4,66.7,108.2,110.0,151.0,154.2.
Embodiment 3
P-nethoxyaniline and 5-HMF react: weigh and get 63.0mg5-HMF, 61.6mg P-nethoxyaniline, and 3.0mg catalyzer measures 1.0mL solvent.System hydrogen pressure is 1.0Mpa, and temperature is 80 DEG C, and the reaction times is 4h.Reaction terminates rear underpressure distillation and removes solvent, and adopt silicagel column separated product (5-(((4-methoxyphenyl) amino) methyl) furan-2-yl) methanol, yield reaches as high as 91%.
(5-(((4-methoxyphenyl) amino) methyl) furan-2-yl) methanol 1hNMR spectrogram 13cNMR spectrogram as shown in Figure 5 and Figure 6, as seen from the figure:
1HNMR(CDCl 3,400MHz)δ3.27(brs,2H,NHandOH),3.73(s,3H,OMe),4.21(s,2H,CH 2NH),4.51(s,2H,CH 2OH),6.14(d,J＝3.1Hz,1H,furanH),6.17(d,J＝3.1Hz,1H,furanH),6.61-6.79(m,4H,ArH)； 13CNMR(CDCl 3,100MHz)δ42.6,55.8,57.3,107.8,108.5,114.85,114.86,141.7,152.6,153.0,153.5.
Embodiment 4
N-methylbenzylamine and 5-HMF react: weigh and get 63.0mg5-HMF, 100.2mgN-methylbenzylamine, and 1.5mg catalyzer measures 1.0mL solvent.System hydrogen pressure is 1.5Mpa, and temperature is 100 DEG C, and the reaction times is 12h.Reaction terminates rear underpressure distillation and removes solvent, and adopt silicagel column separated product (5-((benzyl (methyl) amino) methyl) furan-2-yl) methanol, yield reaches as high as 74%.
(5-((benzyl (methyl) amino) methyl) furan-2-yl) methanol 1hNMR spectrogram 13cNMR spectrogram as shown in Figure 7 and Figure 8, as seen from the figure:
1HNMR(CDCl 3,400MHz)δ2.23(s,3H,Me),3.53(s,2H,CH 2N),3.55(s,2H,CH 2N),4.57(s,2H,CH 2OH),6.15(d,J＝3.1Hz,1H,furanH),6.21(d,J＝3.1Hz,1H,furanH),7.23-7.32(m,5H,ArH)； 13CNMR(CDCl 3,100MHz)δ42.1,53.5,57.6,61.3,108.3,109.4,127.1,128.3,129.2,138.5,152.4,153.7。

Claims (8)

1. synthesize a method for 2-methylol-5-amine methyl furan compounds, it is characterized in that carrying out according to following steps:
Take divalent ruthenium title complex, amine substrate, 5 hydroxymethyl furfural be dissolved in solvent, take 5 hydroxymethyl furfural as raw material, hydrogen is reductive agent, divalent ruthenium title complex is catalyzer, carry out reductive amination process, wherein the ratio of amine substrate, divalent ruthenium title complex, 5 hydroxymethyl furfural amount of substance is 1.0 ~ 2.0:0.001 ~ 0.01:1; Hydrogen pressure is 1.0 ~ 2.0Mpa; Temperature of reaction is 30 ~ 100 DEG C; Reaction times is: 4 ~ 36h; Synthesis 2-methylol-5-amine methyl furan compounds.
2., according to a kind of method of synthesizing 2-methylol-5-amine methyl furan compounds according to claim 1, it is characterized in that described amine substrate is primary amine or secondary amine.
3., according to a kind of method of synthesizing 2-methylol-5-amine methyl furan compounds according to claim 2, it is characterized in that described primary amine structural formula is:
Wherein R 1=ortho position, the substituting group of a position and contraposition, comprises H, F, Cl, Br, Me, OMe, OH or NH 2.
4., according to a kind of method of synthesizing 2-methylol-5-amine methyl furan compounds according to claim 2, it is characterized in that described secondary amine structural formula is:
Wherein, R 2=ortho position, the substituting group of a position and contraposition, comprises H, F, Cl, Br, Me, OMe, OH or NH 2
R 3=Me, Et, n-Pr, i-Pr or n-Bu;
X=CH 2, O, NH or NR 3;
N＝0～10,m＝0～10。
5., according to a kind of method of synthesizing 2-methylol-5-amine methyl furan compounds according to claim 1, it is characterized in that described divalent ruthenium complex structure formula is:
6., according to a kind of method of synthesizing 2-methylol-5-amine methyl furan compounds according to claim 1, it is characterized in that the structural formula of described synthesized 2-methylol-5-amine methyl furan compounds is:
Wherein, R 1=ortho position, the substituting group of a position and contraposition, comprises H, F, Cl, Br, Me, OMe, OH or NH 2
R 2=Me, Et, n-Pr, i-Pr or n-Bu;
X=CH 2, O, NH or NR 3;
N＝0～10,m＝0～10。
7. according to a kind of method of synthesizing 2-methylol-5-amine methyl furan compounds according to claim 1, it is characterized in that described solvent is methyl alcohol, ethanol, ethylene glycol, water, benzene, toluene, methylene dichloride, dimethyl sulfoxide (DMSO), DMF, ethyl acetate, tetrahydrofuran (THF), acetonitrile or chloroform.
8., according to a kind of method of synthesizing 2-methylol-5-amine methyl furan compounds according to claim 1, it is characterized in that described 5 hydroxymethyl furfural concentration is 50 – 200gL -1.
CN201410484223.XA 2014-09-22 2014-09-22 2-hydroxymethyl-5-aminomethyl-furan compound synthesis method Pending CN105503791A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410484223.XA CN105503791A (en) 2014-09-22 2014-09-22 2-hydroxymethyl-5-aminomethyl-furan compound synthesis method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410484223.XA CN105503791A (en) 2014-09-22 2014-09-22 2-hydroxymethyl-5-aminomethyl-furan compound synthesis method

Publications (1)

Publication Number Publication Date
CN105503791A true CN105503791A (en) 2016-04-20

Family

ID=55712160

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410484223.XA Pending CN105503791A (en) 2014-09-22 2014-09-22 2-hydroxymethyl-5-aminomethyl-furan compound synthesis method

Country Status (1)

Country Link
CN (1) CN105503791A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107602512A (en) * 2017-09-25 2018-01-19 南昌大学 A kind of method that one kettle way prepares N (5 methyl furfuryl group) aniline
CN107721953A (en) * 2017-11-06 2018-02-23 南昌大学 A kind of method that one kettle way prepares N (5 methyl furfuryl group) benzylamine

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010020556A1 (en) * 2008-08-22 2010-02-25 Evotec Neurosciences Gmbh New bradykinin b1 antagonists
CN102731577A (en) * 2012-06-18 2012-10-17 广东药学院 Synthetic method for ruthenium metal complex

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010020556A1 (en) * 2008-08-22 2010-02-25 Evotec Neurosciences Gmbh New bradykinin b1 antagonists
CN102731577A (en) * 2012-06-18 2012-10-17 广东药学院 Synthetic method for ruthenium metal complex

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHRISTOPH MǓLLER 等: "Building Blocks from Sugars. Part 23.Hydrophilic 3-Pyridinols from Fructose and Isomaltulose", 《TETRAHEDRON》 *
L. HIZARTZIDIS 等.: "Chemoselective flow hydrogenation approaches to isoindole-7-carboxylic acids and 7-oxa-bicyclio [2.2.1]heptanes", 《RSC ADV.》 *
LEI HUANG 等: "Selective and recyclable rhodium nanocatalysts for the reductive N-alkylation of nitrobenzenes and amines with aldehydes", 《RSC ADV.》 *
ZHANWEI XU 等: "Direct reductive amination of 5-hydroxymethylfurfural with primary/secondary amines via Ru-complex catalyzed hydrogenation", 《RSC ADV.》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107602512A (en) * 2017-09-25 2018-01-19 南昌大学 A kind of method that one kettle way prepares N (5 methyl furfuryl group) aniline
CN107721953A (en) * 2017-11-06 2018-02-23 南昌大学 A kind of method that one kettle way prepares N (5 methyl furfuryl group) benzylamine

Similar Documents

Publication Publication Date Title
Xu et al. Direct reductive amination of 5-hydroxymethylfurfural with primary/secondary amines via Ru-complex catalyzed hydrogenation
Li et al. Thiazolium-derived N-heterocyclic carbene-catalyzed cross-coupling of aldehydes with unactivated imines
Liu et al. Palladium-catalyzed dearomatizing 2, 5-alkoxyarylation of furan rings: diastereospecific access to spirooxindoles
He et al. N-heterocyclic carbene-catalyzed formal cross-coupling reaction of α-haloenals with thiols: Organocatalytic construction of sp 2 carbon–sulfur bonds
Zhang et al. Aryl-palladium-NHC complex: efficient phosphine-free catalyst precursors for the carbonylation of aryl iodides with amines or alkynes
Battini et al. Unexplored reactivity of 2-oxoaldehydes towards Pictet–Spengler conditions: Concise approach to β-carboline based marine natural products
Han et al. Organocatalytic Asymmetric Mannich Reactions of 5H‐Oxazol‐4‐ones: Highly Enantio‐and Diastereoselective Synthesis of Chiral α‐Alkylisoserine Derivatives
Shi et al. Synthesis of functionalized isoquinolin-1 (2H)-ones by copper-catalyzed α-arylation of ketones with 2-halobenzamides.
CN103319311A (en) Preparation method of crizotinib intermediate (1S)-1-(2, 6-dichloro-3-fluorophenyl)ethanol
Ma et al. Synthesis of Benzimidazoles through Palladium‐Catalyzed Amination of 2‐Iodobenzimines with Diaziridinone
Wang et al. An enantioselective aza-Henry reaction of trifluoromethyl ketimines catalyzed by phase-transfer catalysts
CN105503791A (en) 2-hydroxymethyl-5-aminomethyl-furan compound synthesis method
CN103420908A (en) Preparation method of montelukast chiral intermediate
Huang et al. Asymmetric copper-catalyzed propargylic amination with amine hydrochloride salts
Li et al. Synthesis of 1, 4-enyne-3-ones via palladium-catalyzed sequential decarboxylation and carbonylation of allyl alkynoates
EP3008049A1 (en) Process for the production of furanic compounds comprising at least one amine function
CN104262264A (en) New preparation technique of urapidil hydrochloride
CN105712922A (en) Synthetic method of dihydropyrrole and pyrrole compounds
Cheng et al. FeCl 3-catalyzed cyclization of α-sulfonamido-allenes with aldehydes—the substituent effect
Gupta et al. Diastereoselective multi-component tandem condensation: synthesis of 2-amino-4-(2-furanone)-4 H-chromene-3-carbonitriles
CN112552184B (en) Synthetic method of cyclopropyl-containing chiral amine hydrochloride
CN104151283B (en) One catalyzes and synthesizes the method for 12-aryl-8,9,10,12-tetrahydro benzo [α] xanthene-11-ketone derivatives
CN102702207A (en) Method for preparing imidazole isobenzazole compound
CN104311484A (en) Quinoline derivative efficient catalytic synthesis method
CN105622554A (en) Method for preparing 2-hydroxymethyl-5-amine methyl furan compound by fructose

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20160420