Method for preparing quinoline derivative by one-pot two-step method
阅读说明：本技术 一种一锅两步法制备喹啉衍生物的方法 (Method for preparing quinoline derivative by one-pot two-step method ) 是由 王峰 张超锋 于 2018-07-27 设计创作，主要内容包括：本发明涉及一种一锅两步法制备喹啉衍生物的方法。该方法以芳香硝基化合物和脂肪醇为原料,以含氧二硫化钼为催化剂,首先在0.3～3.0MPa氢气、120～160℃条件下反应2～10h,将芳香硝基化合物转化为芳香胺,随后置换反应气氛,在惰性气氛或者在含氧的气氛、120～200℃条件下反应2～12h,反应完成后,分离液相成分,浓缩,经硅胶柱分离,得到取代喹啉化合物。该合成方法在喹啉化合物合成方面可能有重要的应用。(The invention relates to a method for preparing quinoline derivatives by a one-pot two-step method. The method comprises the steps of taking an aromatic nitro compound and aliphatic alcohol as raw materials, taking oxygen-containing molybdenum disulfide as a catalyst, firstly reacting for 2-10 hours under the conditions of hydrogen pressure of 0.3-3.0 MPa and temperature of 120-160 ℃, converting the aromatic nitro compound into aromatic amine, then replacing reaction atmosphere, reacting for 2-12 hours under the conditions of inert atmosphere or oxygen-containing atmosphere and temperature of 120-200 ℃, separating liquid phase components after the reaction is finished, concentrating, and separating by using a silica gel column to obtain the substituted quinoline compound. The synthesis method can be applied to the synthesis of quinoline compounds.)
1. A method for preparing quinoline derivatives by a one-pot two-step method is characterized by comprising the following steps: taking an aromatic nitro compound and aliphatic alcohol as raw materials, taking oxygen-containing molybdenum disulfide as a catalyst, reacting for 2-10 h in an organic reaction solvent under the conditions of 0.3-3.0 MPa of hydrogen and 120-160 ℃, converting the aromatic nitro compound into aromatic amine, then replacing the reaction atmosphere, reacting for 2-12 h in an inert atmosphere or an oxygen-containing atmosphere at 120-200 ℃, separating liquid phase components after the reaction is finished, concentrating, and separating by a silica gel column to obtain the substituted quinoline compound.
2. The method of claim 1, wherein:
the aromatic nitro compound is one or more than two of the following structures:
(1) nitrobenzene and nitrobenzene substituent Rx-(C6H5-X)-NO2(x ═ 1 to 5), wherein R represents various substituents (R ═ H, F, Cl, Br, I, CH3，OCH3，NH2，NO2One to five of CHO, Ph, etc.), X represents the number of substituents, when X represents the number of substituents>1, R may represent the same substituent or different substituents;
(2) the compound of aromatic condensed ring H is substituted by mononitro, wherein the aromatic condensed ring can be one or two of naphthalene ring and anthracene ring;
(3) the compound of the aromatic heterocyclic ring H substituted by the mononitro group, wherein the aromatic heterocyclic ring can be one or more of a pyridine ring, a thiophene ring, a furan ring and an imidazole ring.
3. The method of claim 1, wherein: the aliphatic alcohol is H (CH)2)nCH2CH3One or more of OH (0. ltoreq. n.ltoreq.6, preferably 0. ltoreq. n.ltoreq.2).
4. The method of claim 1, wherein: containing oxygen bisThe catalyst of molybdenum sulfide is MoS2-xOy0.001. ltoreq. x.ltoreq.0.4 and 0.001. ltoreq. y.ltoreq.0.2, preferably 0.002. ltoreq. x.ltoreq.0.1 and 0.002. ltoreq. y.ltoreq.0.1, in the catalyst.
5. The process of claim 1, wherein the solvent for the reaction is one or more selected from toluene, p-xylene, m-xylene, mesitylene and dodecane.
6. The method of claim 1, wherein: the concentration of the substrate aromatic nitro compound in the organic reaction solvent is 0.05-2 mol/L and 0.1-0.5 mol/L; the amount of the fatty alcohol substance is 10-30 times, preferably 15-30 times of that of the aromatic nitro compound; the dosage of the catalyst is 0.5-30 w%, preferably 5-20 w% of the mass of the aromatic nitro compound substrate; the first step is carried out at the reaction temperature of 120-180 ℃, preferably 120-160 ℃, for 2-10 h, preferably 4-10 h; the reaction temperature of the second step is 120-200 ℃, preferably 160-180 ℃, and the reaction time is 2-12 hours, preferably 2-10 hours.
7. The method of claim 1, wherein: the first step is that the reaction atmosphere is hydrogen, the pressure is 0.3-3.0 MPa, and preferably 0.5-1.0 MPa; the second reaction atmosphere may be a pure inert atmosphere, preferably N2Ar or the mixed gas of the two under the pressure of 0.1-3 MPa, preferably 0.1-1.0 MPa, or the second step reaction is carried out in the atmosphere containing oxygen, preferably air or O2Or a mixed gas atmosphere of the two, the pressure is 0.1 to 1MPa, preferably 0.3 to 0.5 MPa.
8. The method of claim 1, wherein: the aromatic nitro compound is preferably nitrobenzene and nitrobenzene substituent Rx-(C6H5-X)-NO2(x＝1～2)。
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing quinoline derivatives by a one-pot two-step method.
Background
Quinolines and their derivatives are an important class of organic compounds, which are widely used in the synthesis of functional drugs, pesticides, dyes, chemical agents, optical materials, functional polymers, and the like (Andries K et al science.2005; 307(5707): 223-27; Theraladanon C et al tetrahedron: asymmetry.2005; 16(4): 827-31; Roma G et al European Journal of medical chemistry.2000; 35(11): 1021-35; Zhang X J et al macromolecules.1999; 32(22): 7422-29). The synthesis method thereof has been widely noticed by people, whereinOrganic multiplex reactions Skraup reactions (Organic reactions.1953; 7:59-98), Doebner reactions (J.chem.Soc.1934:1520-23), Doebner-Von Miller reactions (Berichtedder deutschen Chemischen Gelschaft.1883; 6(2):2464-72), Combes reactions (J.chem.Soc.1927: 2-18357), Conrad-Limpach reactions (chem.Rev.1942; 30(1):113-44),
However, this strategy for the direct synthesis of quinolines has subsequently proven to be rather difficult, mainly due to the complexity of the tandem reaction. So far, only a few have used homogeneous Ru (chem. Soc. Jpn.1984,57,435-438), Rh (Organometallics 1982,1,1003-1006) compounds and heterogeneous Ir/TiO2(Angew. chem. int. Ed.2011,50,10216-10220) and Pt-Sn/Al2O3Catalytic systems (Chin.J.Catal.2013,33, 1423-1426). And TiO2acidified-TiO2、N-doping TiO2And TiO2The noble metal supported photocatalytic system (Arab J Chem 2017,10, S28-S34, ACS Catal.2013,3, 565-. By way of analysis, one economically viable solution is to use a non-noble metal heterogeneous catalyst that is inexpensive, readily available, and stable to achieve the direct conversion process. Or the reaction is divided into two steps, under the condition that the catalyst and the solvent are not changed, the hydrogenation of the aromatic nitro compound is realized to be converted into the aromatic amine in the first step, the conversion of the aliphatic alcohol is realized by changing the reaction atmosphere in the second step, and meanwhile, the selection of the aniline and the carbonyl compound intermediate generated in situ is realizedAnd (4) carrying out a sexual reaction to generate the quinoline compound.
The invention relates to a method for preparing quinoline derivatives by a one-pot two-step method. The method comprises the steps of taking an aromatic nitro compound and aliphatic alcohol as raw materials, taking oxygen-containing molybdenum disulfide as a catalyst, firstly reacting for 2-10 hours under the conditions of hydrogen pressure of 0.3-3.0 MPa and temperature of 120-160 ℃, converting the aromatic nitro compound into aromatic amine, then replacing reaction atmosphere, reacting for 2-12 hours under the conditions of inert atmosphere or oxygen-containing atmosphere and temperature of 120-200 ℃, separating liquid phase components after the reaction is finished, concentrating, and separating by using a silica gel column to obtain the substituted quinoline compound. The synthesis method can be applied to the synthesis of quinoline compounds.
Disclosure of Invention
The invention relates to a method for preparing quinoline derivatives by a one-pot two-step method. The method comprises the steps of taking an aromatic nitro compound and aliphatic alcohol as raw materials, taking oxygen-containing molybdenum disulfide as a catalyst, firstly reacting for 2-10 hours under the conditions of hydrogen pressure of 0.3-3.0 MPa and temperature of 120-160 ℃, converting the aromatic nitro compound into aromatic amine, then replacing reaction atmosphere, reacting for 2-12 hours under the conditions of inert atmosphere or oxygen-containing atmosphere and temperature of 120-200 ℃, separating liquid phase components after the reaction is finished, concentrating, and separating by using a silica gel column to obtain the substituted quinoline compound.
For aromatic nitro compounds, it may be: (1) nitrobenzene and nitrobenzene substituent Rx-(C6H5-X)-NO2(x ═ 1 to 5), wherein R represents various substituents (R ═ H, F, Cl, Br, I, CH3，OCH3，NH2，NO2CHO, Ph, etc.), X represents the number of substituents. When X is present>1 is the same substituent that R may represent or different substituents; (2) nitro compounds with benzene rings substituted by other aromatic condensed rings, wherein the other aromatic condensed rings can be one or more of naphthalene rings, anthracene rings and the like; (3) the nitro compound with the benzene ring substituted by the aromatic heterocyclic ring can be one or more of a pyridine ring, a thiophene ring, a furan ring, an imidazole ring and the like.
For fatty alcohols, the fatty alcohol is H (CH)2)nCH2CH3One or more of OH (n is more than or equal to 0 and less than or equal to 6). When n is>2 is, in addition to a linear alkane substituent, a substituent having a branch.
The catalyst containing molybdenum disulfide oxide is MoS2-XOyBy controlling the sulfuration and reduction degree of the molybdate precursor, x is more than or equal to 0 and less than or equal to 0.4 and y is more than or equal to 0 and less than or equal to 0.2 in the obtained catalyst. Regarding the preparation method of the molybdenum sulfide catalyst: ammonium molybdate and/or sodium molybdate are/is taken as a precursor, thiourea and/or sodium sulfide is taken as a sulfur source, and the formula is shown in the specification(Mo):n(S)Dispersing the catalyst in an aqueous solution according to a molar ratio of 1: 3-1: 30, carrying out hydrothermal treatment at 160-240 ℃ for 6-72 h, filtering and washing to obtain the catalyst. Wherein, the effect of taking ammonium molybdate as a precursor is better than that of sodium molybdate, thiourea in the sulfur source is cheap and easy to control and decompose, and is more suitable in the process of preparing molybdenum sulfide materials, and the synthesis of the catalyst is optimized: according to n(Mo):n(S)The feeding is carried out at a molar ratio of 1: 6-1: 30, and the hydrothermal treatment is carried out at 160-220 ℃ for 12-48 h.
The solvent for the reaction may be one or more of toluene, p-xylene, m-xylene, mesitylene and dodecane.
Aiming at specific synthesis conditions, the concentration of the substrate aromatic nitro compound is 0.05-2 mol/L; the amount of the fatty alcohol substance is 10-30 times of that of the aromatic nitro compound; the dosage of the catalyst is 0.5-20 w% of the mass of the aromatic nitro compound substrate; the first step is carried out at the reaction temperature of 120-160 ℃ for 2-10 h; the reaction temperature of the second step is 120-200 ℃, and the reaction time is 2-12 h. Regarding atmosphere conversion mainly involved in a one-pot two-step method, the reaction atmosphere in the first step is hydrogen, and the pressure is 0.3-3.0 MPa; the second reaction atmosphere may be a pure inert atmosphere, N2Ar or the mixed gas of the Ar and the Ar, the pressure is 0.1-3 MPa, or the second step reaction is carried out in air or O2The reaction is carried out under the atmosphere, and the pressure is 0.1-1 MPa.
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing a quinoline compound through oxidation-reduction integration.
Drawings
FIG. 1 commercial MoS2 (Black 2H-MoS)2) And MoS2-xOy(180-24h) (Red O-MoS)2) Raman mapping of (a). Contrast display MoS2-xOy(180-24h) obvious crystal lattice oxygen residue or doping.
FIG. 2.MoS2-xOy(180-24h) EDX elemental analysis, the catalyst after analysis being expressed in MoS form1.73O0.1(180-24h)。
FIG. 3 shows a reaction equation for preparing quinoline derivatives by a one-pot two-step method.
The specific implementation mode is as follows:
in order to further explain the present invention in detail, several specific embodiments are given below, but the present invention is not limited to these embodiments.
First, for the convenience of expressing the catalyst used, the relevant catalyst will be described. MoSxThe base catalyst is synthesized hydrothermally. Commercial ammonium molybdate and thiourea according to n(Mo):n(S)The mixture was added to a 150mL stainless steel autoclave lined with tetrafluoro at 1:3 to 1:30, and 90mL deionized water was added with stirring. And then the sealed stainless steel autoclave is placed in an oven at 160-250 ℃ for treatment for 12-48 h. After the treatment is finished, the reaction kettle is naturally cooled to room temperature, and the black solid is washed by deionized water and absolute ethyl alcohol. The catalyst obtained was named MoS2-xOy(m-nh), wherein m represents the temperature of the treatment and n represents the time of the treatment. In order to verify whether the catalyst contains lattice oxygen residues or incorporation, the resulting catalyst was first characterized using Raman spectroscopy, followed by characterization of the oxygen content in the catalyst using EDX electron microscopy characterization techniques. MoS2-xOy(m-n h), the correlation results are plotted for the x and y parameters of the catalyst. In MoS2-xOy(180-24h), wherein FIG. 1 is a Raman spectrum diagram and FIG. 2 is an element distribution diagram.
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