(一)技术领域(1) Technical field
本发明涉及一种醇氧化制备醛/酮的方法，具体涉及一种利用铁盐作催化剂、TEMPO(2,2,6,6-四甲基哌啶-氮-氧化物)作助催化剂、氨基酸作配体、氧气或空气作氧化剂的醇氧化制备醛/酮的新方法。The invention relates to a method for preparing aldehyde/ketone by oxidation of alcohol, in particular to a method using iron salt as a catalyst, TEMPO (2,2,6,6-tetramethylpiperidine-nitrogen-oxide) as a cocatalyst, amino acid A new method for the preparation of aldehydes/ketones by oxidation of alcohols as ligands and oxygen or air as oxidant.
(二)背景技术(2) Background technology
醇类化合物的选择性氧化制备相应的醛或酮是有机化学及化工中非常重要的一类反应。[Sheldon,R.A.Kochi，J.K.Metal-Catalyzed Oxidation of Organic Compounds,Academic Press,New York,1981]。这是因为醛或酮在农药、医药以及香料的合成中是一类十分重要的中间体，并且有些醛酮本身就是香料的重要成分。世界上每年生产的羰基化合物超过107吨，其中大多数由醇直接氧化得到。在众多醇氧化反应中，氧气是最具有吸引力的氧化剂，因为氧气不仅具有丰富、廉价、易得等特点，并且其最终产物为水，不会对环境造成污染，亦不会对产物造成二次污染，符合可持续发展和“绿色化学”的理念。[E.,Modern Oxidation Methods,Wiley-VCH,2004]。但是氧气在常温常压下性质稳定，所以直接用氧气来实现醇的选择性氧化是十分困难的。为此，人们发展了各种过渡金属催化剂如钌、钯、金、铂等金属复合物类的催化剂，用于醇的有氧氧化。但是这些金属催化剂存在着价格昂贵，所用辅助配体制备困难，不易修饰等缺点。The selective oxidation of alcohols to the corresponding aldehydes or ketones is a very important class of reactions in organic chemistry and chemical engineering. [Sheldon, RA Kochi, JK Metal-Catalyzed Oxidation of Organic Compounds, Academic Press, New York, 1981]. This is because aldehydes or ketones are very important intermediates in the synthesis of pesticides, medicines and fragrances, and some aldehydes and ketones are themselves important components of fragrances. The annual production of carbonyl compounds in the world exceeds 107 tons, most of which are obtained by direct oxidation of alcohols. In many alcohol oxidation reactions, oxygen is the most attractive oxidant, because oxygen is not only rich, cheap, and easy to obtain, but also its final product is water, which will not pollute the environment or cause secondary pollution to the product. Secondary pollution, in line with the concept of sustainable development and "green chemistry". [E. , Modern Oxidation Methods, Wiley-VCH, 2004]. However, oxygen is stable at normal temperature and pressure, so it is very difficult to directly use oxygen to realize the selective oxidation of alcohols. For this reason, various transition metal catalysts such as ruthenium, palladium, gold, platinum and other metal complex catalysts have been developed for the aerobic oxidation of alcohols. However, these metal catalysts are expensive, difficult to prepare auxiliary ligands, and difficult to modify.
铁作为地壳中含量最丰富的过渡金属，其盐及复合物被广泛应用于催化反应。如2002年，Marti课题组[S.E.Martin and D.F.Suárez,Tetrahedron Lett.,2002,43,4475.]首次利用FeNO3·9H2O/FeBr3为催化剂，乙腈为溶剂，室温下可实现二级脂肪醇及苄醇的选择性氧化。梁鑫淼课题组[N.Wang,R.Liu,J.Chen and X.Liang,Chem.Commun.,2005,5322；X.Wang and X.Liang,Chin.J.Catal.,2008,29,935；W.Yin,C.Chu,Q.Lu,J.Tao,X.Liangand R.Liu,Adv.Synth.Catal.2010,352,113.W.Yin,C.Chu,Q.Lu,J.Tao,X.Liang andR.Liu,Adv.Synth.Catal.2010,352,113.]先后分别利用FeCl3·6H2O/TEMPO/NaNO2、FeNO3·9H2O/4-OH-TEMPO以及FeCl3/4-acetamido-TEMPO/NaNO2等体系实现了醇的空气(或氧气)氧化反应。该方法可以选择性氧化一级、二级苄醇以及烯丙醇。最近麻生明课题组[(a)S.Ma,J.Liu,S.Li,B.Chen,J.Cheng,J.Kuang,Y.Liu,B.Wan,Y.Wang,J.Ye,Q.Yu,W.Yuan and S.Yu,Adv.Synth.Catal.2011,353,1005；(b)Liu,J.；Ma,S.,Org.Biomol.Chem.2013,11,4186；(c)Liu,J.；Ma,S.,Tetrahedron 2013,69(47),10161；(d)Liu,J.；Ma,S.,Org.Lett.2013,15,5150.]发展了FeNO3·9H2O/TEMPO/NaCl催化体系，通过调整各组分的比例可以实现连烯醇、炔丙醇、苄醇以及高炔丙醇的选择性氧化。尽管这些铁催化体系有较好的效果，但他们有一个共同的缺点，即这些体系中的铁催化剂仅限于FeNO3或必须使用NaNO2启动基于NO/NO2的催化循环来活化利用氧气。当采用FeNO3以外的铁盐，并且不加NaNO2时，反应均无法进行。[R.Liu,X.Liang,C.Dong and X.Hu,J.Am.Chem.Soc.,2004,126,4112.]。此外这些体系均为酸性，对酸敏感的底物无法适用，底物范围较受限制。Iron is the most abundant transition metal in the earth's crust, and its salts and complexes are widely used in catalytic reactions. For example, in 2002, the Marti research group [SEMartin and DF Suárez, Tetrahedron Lett., 2002, 43, 4475.] used FeNO3 9H2 O/FeBr3 as a catalyst for the first time, and acetonitrile as a solvent, and the secondary aliphatic alcohol and Selective oxidation of benzyl alcohol. Liang Xinmiao's research group [N.Wang, R.Liu, J.Chen and X.Liang, Chem.Commun., 2005, 5322; X.Wang and X.Liang, Chin.J.Catal., 2008, 29,935; W. Yin, C. Chu, Q. Lu, J. Tao, X. Liang and R. Liu, Adv. Synth. Catal. 2010, 352, 113. W. Yin, C. Chu, Q. Lu, J. Tao, X. Liang andR.Liu, Adv.Synth.Catal.2010,352,113.] using FeCl3 ·6H2 O/TEMPO/NaNO2 , FeNO3 ·9H2 O/4-OH-TEMPO and FeCl3 /4-acetamido- TEMPO/NaNO2 and other systems realize the air (or oxygen) oxidation reaction of alcohols. The method can selectively oxidize primary and secondary benzyl alcohol and allyl alcohol. Recently, Ma Shengming's research group [(a) S.Ma, J.Liu, S.Li, B.Chen, J.Cheng, J.Kuang, Y.Liu, B.Wan, Y.Wang, J.Ye, Q .Yu, W.Yuan and S.Yu, Adv.Synth.Catal.2011, 353, 1005; (b) Liu, J.; Ma, S., Org.Biomol.Chem.2013, 11, 4186; (c ) Liu, J.; Ma, S., Tetrahedron 2013, 69(47), 10161; (d) Liu, J.; Ma, S., Org. Lett.2013, 15, 5150.] developed FeNO3 · The 9H2 O/TEMPO/NaCl catalytic system can realize the selective oxidation of allenyl alcohol, propargyl alcohol, benzyl alcohol and homopropargyl alcohol by adjusting the ratio of each component. Although these iron-catalyzed systems have good results, they have a common disadvantage that the iron catalysts in these systems are limited toFeNO3 or NaNO2 must be used to initiate a NO/NO2- based catalytic cycle to activate the utilization of oxygen. When iron salts other than FeNO3 were used and NaNO2 was not added, the reaction could not proceed. [R. Liu, X. Liang, C. Dong and X. Hu, J. Am. Chem. Soc., 2004, 126, 4112.]. In addition, these systems are all acidic, and cannot be applied to acid-sensitive substrates, and the scope of substrates is relatively limited.
(三)发明内容(3) Contents of the invention
本发明旨在提供一种以廉价易得、对环境友好的铁盐作催化剂，TEMPO作助催化剂，氨基酸作配体，氧气或空气作氧化剂氧化醇制备相应醛/酮的新方法。The present invention aims to provide a new method for preparing corresponding aldehyde/ketone by oxidizing alcohol with cheap, easy-to-obtain and environment-friendly iron salt as catalyst, TEMPO as co-catalyst, amino acid as ligand and oxygen or air as oxidant.
为实现上述目的，本发明采用如下技术方案：To achieve the above object, the present invention adopts the following technical solutions:
一种铁盐催化醇氧化制备醛/酮的方法，所述方法为：A kind of method that iron salt catalyzes alcohol oxidation to prepare aldehyde/ketone, described method is:
将底物式(I)所示化合物、催化剂铁盐、助催化剂TEMPO、氨基酸配体和溶剂混合后，在氧气或空气(一般为常压)气氛中回流搅拌1～60h(优选12～36h)，之后反应液经后处理得到产物式(II)所示化合物；After mixing the compound represented by the substrate formula (I), the catalyst iron salt, the cocatalyst TEMPO, the amino acid ligand and the solvent, reflux and stir in an atmosphere of oxygen or air (generally normal pressure) for 1 to 60 hours (preferably 12 to 36 hours) Afterwards, the reaction solution obtains the compound shown in the product formula (II) through aftertreatment;
所述底物式(I)所示化合物与催化剂铁盐、助催化剂TEMPO、氨基酸配体的投料物质的量之比为1：0.01～0.5：0.01～0.3：0.01～0.5；The ratio of the amount of the substrate compound represented by the formula (I) to the catalyst iron salt, cocatalyst TEMPO, and amino acid ligand is 1:0.01～0.5:0.01～0.3:0.01～0.5;
所述铁盐为氯化铁、氯化亚铁、硫酸铁、硫酸亚铁、乙酰丙酮铁、乙酰丙酮亚铁、高氯酸铁、氟化铁、氟化亚铁、三氟甲磺酸铁、三氟甲磺酸亚铁、溴化铁、溴化亚铁、醋酸铁或醋酸亚铁；The iron salt is ferric chloride, ferrous chloride, ferric sulfate, ferrous sulfate, ferric acetylacetonate, ferrous acetylacetonate, ferric perchlorate, ferric fluoride, ferrous fluoride, ferric trifluoromethanesulfonate , ferrous trifluoromethanesulfonate, ferric bromide, ferrous bromide, ferric acetate or ferrous acetate;
所述氨基酸配体为L-脯氨酸、L-丙氨酸、L-丝氨酸、L-亮氨酸、L-组氨酸、L-苯丙氨酸、DL-苯丙氨酸、L-天门冬氨酸、DL-天门冬氨酸、L-甲硫氨酸、L-缬氨酸、L-甘氨酸、DL-丙氨酸、L-肌氨酸、L-异亮氨酸、N-乙酰基-L-组氨酸、N-乙酰基-L-半胱氨酸、2-甲基丙氨酸、4-甲氧基苯基甘氨酸、4-甲氧基苯基缬氨酸、L-谷氨酰胺、DL-α-氨基异丁酸、DL-苯丙氨酸、L-苏氨酸、N-乙酰基-L-缬氨酸或N-苯基丙氨酸；The amino acid ligand is L-proline, L-alanine, L-serine, L-leucine, L-histidine, L-phenylalanine, DL-phenylalanine, L- Aspartic acid, DL-aspartic acid, L-methionine, L-valine, L-glycine, DL-alanine, L-sarcosine, L-isoleucine, N- Acetyl-L-histidine, N-acetyl-L-cysteine, 2-methylalanine, 4-methoxyphenylglycine, 4-methoxyphenylvaline, L - glutamine, DL-alpha-aminoisobutyric acid, DL-phenylalanine, L-threonine, N-acetyl-L-valine or N-phenylalanine;
所述溶剂为甲苯、二甲苯、氯苯、正己烷、三氟甲苯、二氯乙烷、二氯甲烷、甲醇、乙醇、异丙醇、叔戊醇、叔丁醇、二氧六环、六氟异丙醇、乙腈、四氢呋喃、丙酮、DMF或DMSO；The solvent is toluene, xylene, chlorobenzene, n-hexane, trifluorotoluene, dichloroethane, dichloromethane, methanol, ethanol, isopropanol, tert-amyl alcohol, tert-butanol, dioxane, hexa Fluoroisopropanol, acetonitrile, tetrahydrofuran, acetone, DMF or DMSO;
式(I)或式(II)中，R1为氢、甲基、甲氧基、甲硫基、氰基、氟、氯、溴、碘、硝基、醚键、炔基、烯基、苯基或三氟甲基；In formula (I ) or formula (II), R is hydrogen, methyl, methoxy, methylthio, cyano, fluorine, chlorine, bromine, iodine, nitro, ether bond, alkynyl, alkenyl, Phenyl or trifluoromethyl;
R2为氢、甲基、乙基、苯基或苯甲酰基；R ishydrogen , methyl, ethyl, phenyl or benzoyl;
X为碳、氮、氧或硫；X is carbon, nitrogen, oxygen or sulfur;
n为0或1；n is 0 or 1;
m为0或1。m is 0 or 1.
需要说明的是，当底物式(I)所示化合物为伯醇时，所得产物式(II)所示化合物为醛；当底物式(I)所示化合物为仲醇时，所得产物式(II)所示化合物为酮。It should be noted that when the compound shown in the substrate formula (I) is a primary alcohol, the compound shown in the product formula (II) is an aldehyde; when the compound shown in the substrate formula (I) is a secondary alcohol, the product formula The compound shown in (II) is a ketone.
本发明所述铁盐催化醇氧化制备醛/酮的方法，优选所述底物式(I)所示化合物与催化剂铁盐、助催化剂TEMPO、氨基酸配体的投料物质的量之比为1：0.05～0.2：0.1～0.3：0.05～0.2。The method for preparing aldehyde/ketone by ferric salt catalyzed oxidation of alcohol of the present invention, the ratio of the amount of feed material of the compound shown in preferred described substrate formula (I) and catalyst ferric salt, cocatalyst TEMPO, amino acid ligand is 1: 0.05-0.2: 0.1-0.3: 0.05-0.2.
优选所述铁盐为氯化铁、氯化亚铁、三氟甲磺酸铁、三氟甲磺酸亚铁、溴化铁或溴化亚铁。Preferably, the iron salt is ferric chloride, ferrous chloride, ferric triflate, ferrous triflate, ferric bromide or ferrous bromide.
优选所述氨基酸配体为L-缬氨酸、DL-丙氨酸、2-甲基丙氨酸、L-苯丙氨酸、L-异亮氨酸、4-甲氧基苯基甘氨酸或4-氯苯基缬氨酸，其结构式分别如下所示：Preferably, the amino acid ligand is L-valine, DL-alanine, 2-methylalanine, L-phenylalanine, L-isoleucine, 4-methoxyphenylglycine or 4-chlorophenylvaline, its structural formula is as follows respectively:
优选所述溶剂为甲苯、三氟甲苯、二甲苯、氯苯、叔戊醇或二氧六环；并且，推荐所述溶剂的体积用量以底物式(I)所示化合物的质量计为10～100mL/g，优选20～40mL/g。Preferably, the solvent is toluene, trifluorotoluene, xylene, chlorobenzene, tert-amyl alcohol or dioxane; and, the volumetric amount of the recommended solvent is 10% based on the mass of the compound shown in the substrate formula (I). ~ 100 mL/g, preferably 20 ~ 40 mL/g.
一般情况下，本发明所述后处理的方法为：反应结束后，反应液冷却至室温，过滤，取滤液蒸除溶剂，剩余物进行柱层析纯化，以正己烷：乙酸乙酯体积比10：1的混合液为洗脱剂，收集含目标化合物的洗脱液，蒸除溶剂后干燥即得产物。Generally speaking, the post-treatment method of the present invention is as follows: after the reaction is finished, the reaction solution is cooled to room temperature, filtered, the filtrate is taken to evaporate the solvent, and the residue is purified by column chromatography. : The mixed solution of 1 is the eluent, the eluent containing the target compound is collected, the solvent is evaporated and dried to obtain the product.
进一步，具体推荐本发明所述铁盐催化醇氧化制备醛/酮的方法为：Further, it is specifically recommended that the method for preparing aldehydes/ketones by the oxidation of alcohols catalyzed by iron salts of the present invention is:
将底物式(I)所示化合物、催化剂铁盐、助催化剂TEMPO、氨基酸配体和溶剂混合后，在氧气或空气(一般为常压)气氛中回流搅拌12～36h，之后反应液冷却至室温，过滤，取滤液蒸除溶剂，剩余物进行柱层析纯化，以正己烷：乙酸乙酯体积比10：1的混合液为洗脱剂，收集含目标化合物的洗脱液，蒸除溶剂后干燥即得产物式(II)所示化合物；After mixing the compound represented by the substrate formula (I), the catalyst iron salt, the cocatalyst TEMPO, the amino acid ligand and the solvent, reflux and stir in an atmosphere of oxygen or air (generally normal pressure) for 12 to 36 hours, and then cool the reaction solution to At room temperature, filter, take the filtrate and evaporate the solvent, and the residue is purified by column chromatography, using a mixture of n-hexane:ethyl acetate with a volume ratio of 10:1 as the eluent, collect the eluate containing the target compound, and evaporate the solvent Post-dry to obtain the compound shown in the product formula (II);
所述底物式(I)所示化合物与催化剂铁盐、助催化剂TEMPO、氨基酸配体的投料物质的量之比为1：0.05～0.2：0.1～0.3：0.05～0.2；The ratio of the amount of the compound represented by the substrate formula (I) to the catalyst iron salt, co-catalyst TEMPO, and amino acid ligands is 1: 0.05-0.2: 0.1-0.3: 0.05-0.2;
所述铁盐为氯化铁、氯化亚铁、三氟甲磺酸铁、三氟甲磺酸亚铁、溴化铁或溴化亚铁。The iron salt is ferric chloride, ferrous chloride, ferric trifluoromethanesulfonate, ferrous trifluoromethanesulfonate, ferric bromide or ferrous bromide.
所述氨基酸配体为L-缬氨酸、DL-丙氨酸、2-甲基丙氨酸、L-苯丙氨酸、L-异亮氨酸、4-甲氧基苯基甘氨酸或4-氯苯基缬氨酸；The amino acid ligand is L-valine, DL-alanine, 2-methylalanine, L-phenylalanine, L-isoleucine, 4-methoxyphenylglycine or 4 - Chlorophenylvaline;
所述溶剂为甲苯、三氟甲苯、二甲苯、氯苯、叔戊醇或二氧六环；所述溶剂的体积用量以底物式(I)所示化合物的质量计为20～40mL/g。The solvent is toluene, trifluorotoluene, xylene, chlorobenzene, tert-amyl alcohol or dioxane; the volumetric amount of the solvent is 20～40mL/g based on the mass of the compound shown in the substrate formula (I) .
本发明的有益效果主要体现在：The beneficial effects of the present invention are mainly reflected in:
(1)使用廉价易得，且对环境友好的铁盐作为催化剂；(1) Use cheap, easy-to-get, and environmentally friendly iron salts as catalysts;
(2)使用自然界中资源丰富，廉价易得且易于修饰的氨基酸作为配体；(2) Use amino acids that are abundant in resources, cheap and easy to obtain and easy to modify in nature as ligands;
(3)反应底物适用性广，一级苄醇、二级苄醇、烯丙醇以及杂环芳醇等采用本发明氧化体系均可以高收率地转化成相应的醛(酮)。(3) The reaction substrate has wide applicability, and primary benzyl alcohol, secondary benzyl alcohol, allyl alcohol and heterocyclic aromatic alcohol can all be converted into corresponding aldehydes (ketones) in high yields by using the oxidation system of the present invention.
(四)具体实施方式(4) Specific implementation methods
下面结合具体实施例对本发明进行进一步描述，但本发明的保护范围并不仅限于此。The present invention will be further described below in conjunction with specific examples, but the protection scope of the present invention is not limited thereto.
实施例1Example 1
在配有磁子搅拌的1L圆底烧瓶中加入对甲基苯甲醇(12.22g，100.0mmol，即式(I)中的R1为4-甲基，R2为氢，X为碳，n为1，m为0)，氯化铁(0.81g，5mmol)，L-异亮氨酸(1.31g，10mmol)，TEMPO(1.56g，10mmol)，甲苯300.0mL，然后用氧气将反应瓶内的空气置换，回流搅拌6h。反应结束后，待反应液冷却至室温，过滤，取滤液蒸除溶剂得到粗产物，所得粗产物进行柱层析纯化，用正己烷：乙酸乙酯(体积比10：1)的混合液洗脱，收集含目标化合物的洗脱液，蒸除溶剂后干燥，得到产物对甲基苯甲醛10.93g，收率为91％。Add p-methylbenzyl alcohol (12.22g, 100.0mmol) in a 1L round bottom flask equipped with magnetic stirring, that is, R in formula (I)1 is 4-methyl, R2 is hydrogen, X is carbon, n is 1, m is 0), ferric chloride (0.81g, 5mmol), L-isoleucine (1.31g, 10mmol), TEMPO (1.56g, 10mmol), toluene 300.0mL, and then use oxygen to Air replacement, reflux and stirring for 6h. After the reaction, the reaction solution was cooled to room temperature, filtered, and the filtrate was evaporated to remove the solvent to obtain a crude product, which was purified by column chromatography and eluted with a mixture of n-hexane:ethyl acetate (volume ratio 10:1) , collected the eluate containing the target compound, evaporated the solvent and dried to obtain 10.93 g of the product p-tolualdehyde with a yield of 91%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ2.38(s,3H),7.27(d,J＝4.3Hz,2H),7.73(d,J＝4.0Hz,2H),9.91(s,1H).1 H NMR (500MHz, CDCl3 ): δ2.38(s, 3H), 7.27(d, J=4.3Hz, 2H), 7.73(d, J=4.0Hz, 2H), 9.91(s ,1H).
核磁共振碳谱13C NMR(125MHz，CDCl3):δ21.5,129.4,129.5,134.0,145.2,191.6.13 C NMR (125MHz, CDCl3 ): δ21.5, 129.4, 129.5, 134.0, 145.2, 191.6.
实施例2Example 2
所用的反应物为对甲氧基苯甲醇(12.22g，100.0mmol，即式(I)中的R1为4-甲氧基，R2为氢，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：氯化亚铁(2.54g，20mmol)，L-异亮氨酸(1.31g，10mmol)，TEMPO(1.56g，10mmol)，氯苯300.0mL，在空气条件下回流搅拌24h。最终得到产物12.53g，收率92％。The reactant used is p-methoxybenzyl alcohol (12.22g, 100.0mmol, that is, R in formula (I)1 is 4-methoxy, R2 is hydrogen, X is carbon, n is 1, m is 0 ), the experimental method and steps are the same as in Example 1, and the difference is: ferrous chloride (2.54g, 20mmol), L-isoleucine (1.31g, 10mmol), TEMPO (1.56g, 10mmol), chlorobenzene 300.0mL, stirred at reflux for 24h under air condition. Finally, 12.53 g of the product was obtained with a yield of 92%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ3.71(s,3H),6.84(d,J＝4.3Hz,2H),7.67(d,J＝4.3Hz,2H),9.72(s,1H).1 H NMR (500MHz, CDCl3 ): δ3.71(s, 3H), 6.84(d, J=4.3Hz, 2H), 7.67(d, J=4.3Hz, 2H), 9.72(s ,1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ55.4,114.2,129.9,131.8,164.6,190.6.13 C NMR (125MHz, CDCl3 ): δ55.4, 114.2, 129.9, 131.8, 164.6, 190.6.
实施例3Example 3
所用的反应物为3,4,5-三甲氧基苯甲醇(12.22g，100.0mmol，即式(I)中的R1为3,4,5-三甲氧基，R2为氢，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：三氟甲磺酸铁(25.15g，50mmol)，2-甲基丙氨酸(5.16g，50mmol)，TEMPO(4.69g，30mmol)，二甲苯300.0mL，用氧气将反应瓶内的空气置换后回流搅拌1h。最终得到产物18.05g，收率92％。The reactant used is 3,4,5-trimethoxybenzyl alcohol (12.22g, 100.0mmol, that is, R in formula (I ) is 3,4,5-trimethoxy, R ishydrogen , X is Carbon, n is 1, m is 0), experimental method and step are with embodiment 1, difference is: iron trifluoromethanesulfonate (25.15g, 50mmol), 2-methylalanine (5.16g, 50mmol ), TEMPO (4.69g, 30mmol), xylene 300.0mL, reflux and stir for 1h after replacing the air in the reaction flask with oxygen. Finally, 18.05 g of the product was obtained with a yield of 92%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ3.89(d,J＝4.0Hz,9H),7.09(s,2H),9.83(s,1H).1 H NMR (500MHz, CDCl3 ): δ3.89(d, J=4.0Hz, 9H), 7.09(s, 2H), 9.83(s, 1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ56.2,60.8,106.7,131.7,143.6,153.6,190.8.13 C NMR (125MHz, CDCl3 ): δ56.2, 60.8, 106.7, 131.7, 143.6, 153.6, 190.8.
实施例4Example 4
所用的反应物为对氟苯甲醇(1.26g，10.0mmol，即式(I)中的R1为4-氟，R2为氢，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：溴化铁(0.03g，0.1mmol)，L-苯丙氨酸(0.17g，1.0mmol)，TEMPO(0.31g，2.0mmol)，三氟甲苯30.0mL，用氧气将反应瓶内的空气置换后回流搅拌24h。最终得到产物1.14g，收率90％。The reactant used is p-fluorobenzyl alcohol (1.26g, 10.0mmol, that is, R in formula (I)1 is 4-fluoro, R2 is hydrogen, X is carbon, n is 1, m is 0), experimental method And step is with embodiment 1, difference is: iron bromide (0.03g, 0.1mmol), L-phenylalanine (0.17g, 1.0mmol), TEMPO (0.31g, 2.0mmol), trifluorotoluene 30.0 mL, replace the air in the reaction bottle with oxygen and then reflux and stir for 24h. Finally, 1.14 g of the product was obtained with a yield of 90%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ7.16-7.20(m,2H),7.87-7.90(m,2H),9.94(s,1H).1 H NMR (500MHz, CDCl3 ): δ7.16-7.20(m, 2H), 7.87-7.90(m, 2H), 9.94(s, 1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ116.3,132.4,133.0,164.8,191.6.13 C NMR (125MHz, CDCl3 ): δ116.3, 132.4, 133.0, 164.8, 191.6.
实施例5Example 5
所用的反应物为邻碘苯甲醇(2.34g，10.0mmol，即式(I)中的R1为2-碘，R2为氢，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：三氟甲磺酸亚铁(0.35g，1.0mmol)，4-甲氧基苯基甘氨酸(0.18g，1.0mmol)，TEMPO(0.16g，1.0mmol)，叔戊醇30.0mL，用氧气将反应瓶内的空气置换后回流搅拌24h。最终得到产物1.97g，收率85％。The reactant used is o-iodobenzyl alcohol (2.34g, 10.0mmol, that is, R in the formula (I ) is2 -iodine, R is hydrogen, X is carbon, n is 1, and m is 0), the experimental method And step is with embodiment 1, difference is: ferrous trifluoromethanesulfonate (0.35g, 1.0mmol), 4-methoxyphenylglycine (0.18g, 1.0mmol), TEMPO (0.16g, 1.0mmol ), tert-amyl alcohol 30.0mL, reflux and stir for 24h after replacing the air in the reaction flask with oxygen. Finally, 1.97 g of the product was obtained with a yield of 85%.
核磁共振氢谱1H NMR(500MHz,CDCl3)δ10.07(s,1H),7.96(d,J＝8.9Hz,1H),7.88(dd,J＝7.7,1.8Hz,1H),7.47(t,J＝7.5Hz,1H),7.33–7.26(m,1H).1 H NMR (500MHz, CDCl3 ) δ10.07(s, 1H), 7.96(d, J=8.9Hz, 1H), 7.88(dd, J=7.7, 1.8Hz, 1H), 7.47( t,J=7.5Hz,1H),7.33–7.26(m,1H).
核磁共振碳谱13C NMR(126MHz,CDCl3)δ195.67,140.62,135.43,135.13,130.24,128.69,100.63.13 C NMR (126MHz, CDCl3 ) δ195.67, 140.62, 135.43, 135.13, 130.24, 128.69, 100.63.
实施例6Example 6
所用的反应物为3-氰基苯甲醇(1.33g，10.0mmol，即式(I)中的R1为3-氰基，R2为氢，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：溴化亚铁(0.11g，0.5mmol)，DL-丙氨酸(0.09g，1mmol)，TEMPO(0.16g，1mmol)，二氧六环30.0mL，用氧气将反应瓶内的空气置换后回流搅拌12h。最终得到产物1.17g，收率89％。The reactant used is 3-cyanobenzyl alcohol (1.33g, 10.0mmol, that is, R in formula (I ) is3 -cyano, R is hydrogen, X is carbon, n is 1, m is 0) , experimental method and step are with embodiment 1, difference is: ferrous bromide (0.11g, 0.5mmol), DL-alanine (0.09g, 1mmol), TEMPO (0.16g, 1mmol), dioxane Ring 30.0mL, replace the air in the reaction flask with oxygen, and then reflux and stir for 12h. Finally, 1.17 g of the product was obtained with a yield of 89%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ7.70(t,J＝8.0Hz,1H),7.91(d,J＝3.8Hz,1H),8.13(d,J＝3.8Hz,1H),8.16(s,1H),10.04(s,1H).1 H NMR (500MHz, CDCl3 ): δ7.70(t, J=8.0Hz, 1H), 7.91(d, J=3.8Hz, 1H), 8.13(d, J=3.8Hz, 1H ),8.16(s,1H),10.04(s,1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ113.7,117.5,130.1,133.1,133.2,136.9,137.1,189.9.13 C NMR (125MHz, CDCl3 ): δ113.7, 117.5, 130.1, 133.1, 133.2, 136.9, 137.1, 189.9.
实施例7Example 7
所用的反应物为4-硝基苯甲醇(1.53g，10.0mmol，即式(I)中的R1为4-硝基，R2为氢，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：氯化铁(0.08g，0.5mmol)，4-氯苯基缬氨酸(0.23g，1.0mmol)，TEMPO(0.16g，1.0mmol)，三氟甲苯30.0mL，用氧气将反应瓶内的空气置换后回流搅拌12h。最终得到产物1.25g，收率83％。The reactant used is 4-nitrobenzyl alcohol (1.53g, 10.0mmol, that is, R in formula (I ) is4 -nitro, R is hydrogen, X is carbon, n is 1, m is 0) , experimental method and step are with embodiment 1, difference is: ferric chloride (0.08g, 0.5mmol), 4-chlorophenylvaline (0.23g, 1.0mmol), TEMPO (0.16g, 1.0mmol) , benzotrifluoride 30.0mL, the air in the reaction bottle was replaced with oxygen and then stirred under reflux for 12h. Finally, 1.25 g of the product was obtained with a yield of 83%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ8.09(d,J＝4.5Hz,2H),8.40(d,J＝4.5Hz,2H),10.17(s,1H).1 H NMR (500MHz, CDCl3 ): δ8.09(d, J=4.5Hz, 2H), 8.40(d, J=4.5Hz, 2H), 10.17(s, 1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ124.3,130.5,140.2,151.3,190.2.13 C NMR (125MHz, CDCl3 ): δ124.3, 130.5, 140.2, 151.3, 190.2.
实施例8Example 8
所用的反应物为2-噻吩甲醇(1.14g，10.0mmol，即式(I)中的R1为氢，R2为氢，X为硫，n为0，m为0)，实验方法和步骤同实施例1，不同之处在于：溴化铁(0.15g，0.5mmol)，L-苯丙氨酸(0.17g，1mmol)，TEMPO(0.16g，1mmol)，氯苯30.0mL，用氧气将反应瓶内的空气置换后回流搅拌12h。最终得到产物1.02g，收率91％。The reactant used is 2-thiophenemethanol (1.14g, 10.0mmol, that is, R in the formula (I ) is hydrogen, R ishydrogen , X is sulfur, n is 0, m is 0), experimental methods and steps With embodiment 1, difference is: iron bromide (0.15g, 0.5mmol), L-phenylalanine (0.17g, 1mmol), TEMPO (0.16g, 1mmol), chlorobenzene 30.0mL, with oxygen After the air in the reaction bottle was replaced, it was refluxed and stirred for 12 hours. Finally, 1.02 g of the product was obtained with a yield of 91%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ7.18-7.20(q,1H),7.74-7.76(m,1H),7.77(dd,J＝1.8Hz,1.5Hz,1H),9.916(d,J＝1.5Hz,1H).1 H NMR (500MHz, CDCl3 ): δ7.18-7.20(q, 1H), 7.74-7.76(m, 1H), 7.77(dd, J＝1.8Hz, 1.5Hz, 1H), 9.916 (d,J=1.5Hz,1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ128.3,135.0,136.3,143.9,182.9.13 C NMR (125MHz, CDCl3 ): δ128.3, 135.0, 136.3, 143.9, 182.9.
实施例9Example 9
所用的反应物为3-吡啶甲醇(1.09g，10.0mmol，即式(I)中的R1为氢，R2为氢，X为氮，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：氯化亚铁(0.06g，0.5mmol)，DL-丙氨酸(0.09g，1mmol)，TEMPO(0.156g，1mmol)，二氧六环30.0mL，用氧气将反应瓶内的空气置换后回流搅拌12h。最终得到产物0.96g，收率90％。The reactant used is 3-pyridinemethanol (1.09g, 10.0mmol, that is, R in formula (I)1 is hydrogen, R2 is hydrogen, X is nitrogen, n is 1, m is 0), experimental methods and steps With embodiment 1, difference is: ferrous chloride (0.06g, 0.5mmol), DL-alanine (0.09g, 1mmol), TEMPO (0.156g, 1mmol), dioxane 30.0mL, with Oxygen replaces the air in the reaction bottle and then reflux and stir for 12h. Finally, 0.96 g of the product was obtained with a yield of 90%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ7.46-7.50(q,1H),8.15-8.18(m,1H),8.82-8.84(q,1H),9.07(d,J＝2.0Hz,1H),10.10(s,1H).1 H NMR (500MHz, CDCl3 ): δ7.46-7.50(q, 1H), 8.15-8.18(m, 1H), 8.82-8.84(q, 1H), 9.07(d, J＝2.0 Hz,1H),10.10(s,1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ124.0,131.4,135.7,151.9,154.6,190.6.13 C NMR (125MHz, CDCl3 ): δ124.0, 131.4, 135.7, 151.9, 154.6, 190.6.
实施例10Example 10
所用的反应物为肉桂醇(1.34g，10.0mmol，即式(I)中的R1为氢，R2为氢，X为碳，n为1，m为1)，实验方法和步骤同实施例1，不同之处在于：三氟甲磺酸铁铁(0.50g，1.0mmol)，L-异亮氨酸(0.13g，1mmol)，TEMPO(0.16g，1mmol)，叔戊醇30.0mL，用氧气将反应瓶内的空气置换后回流搅拌12h。最终得到产物1.18g，收率89％。The reactant used is cinnamyl alcohol (1.34g, 10.0mmol, namely R in formula (I)1 is hydrogen, R2 is hydrogen, X is carbon, n is 1, m is 1), experimental method and step are implemented Example 1, the difference is: iron iron triflate (0.50g, 1.0mmol), L-isoleucine (0.13g, 1mmol), TEMPO (0.16g, 1mmol), tert-amyl alcohol 30.0mL, The air in the reaction flask was replaced with oxygen and then stirred at reflux for 12 h. Finally, 1.18 g of the product was obtained with a yield of 89%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ6.71(q,J＝7.5Hz,1H),7.42(d,J＝2.0Hz,1H),7.43(d,J＝2.0Hz,2H),7.45(d,J＝2.5Hz,1H),7.55(d,J＝2.5Hz,1H),7.56(d,J＝2.0Hz,1H),9.69(d,J＝7.0Hz,1H).1 H NMR (500MHz, CDCl3 ): δ6.71(q, J=7.5Hz, 1H), 7.42(d, J=2.0Hz, 1H), 7.43(d, J=2.0Hz, 2H ),7.45(d,J=2.5Hz,1H),7.55(d,J=2.5Hz,1H),7.56(d,J=2.0Hz,1H),9.69(d,J=7.0Hz,1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ128.5,129.1,131.2,134.0,152.7,193.8.13 C NMR (125MHz, CDCl3 ): δ128.5, 129.1, 131.2, 134.0, 152.7, 193.8.
实施例11Example 11
所用的反应物为4-炔丙基醚苯甲醇(1.62g，10.0mmol，即式(I)中的R1为4-炔丙基醚，R2为氢，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：溴化铁(0.15g，0.5mmol)，2-甲基丙氨酸(0.10g，0.1mmol)，TEMPO(0.16g，1.0mmol)，三氟甲苯30.0mL，用氧气将反应瓶内的空气置换后回流搅拌12h。最终得到产物1.47g，收率92％。The reactant used is 4-propargyl ether benzyl alcohol (1.62g, 10.0mmol, that is, R in formula (I ) is 4-propargyl ether, R ishydrogen , X is carbon, n is 1, m is 0), experimental method and steps are the same as in Example 1, and the difference is: ferric bromide (0.15g, 0.5mmol), 2-methylalanine (0.10g, 0.1mmol), TEMPO (0.16g, 1.0mmol), trifluorotoluene 30.0mL, the air in the reaction flask was replaced with oxygen, and then refluxed and stirred for 12h. Finally, 1.47 g of the product was obtained with a yield of 92%.
核磁共振氢谱1H NMR(500MHz,CDCl3)δ9.92(s,1H),7.88(d,J＝8.8Hz,2H),7.11(d,J＝8.7Hz,2H),4.80(d,J＝2.4Hz,2H),2.58(t,J＝2.4Hz,1H).1 H NMR (500MHz, CDCl3 ) δ9.92(s, 1H), 7.88(d, J=8.8Hz, 2H), 7.11(d, J=8.7Hz, 2H), 4.80(d, J＝2.4Hz, 2H), 2.58(t, J＝2.4Hz, 1H).
核磁共振碳谱13C NMR(126MHz,CDCl3)δ190.74,162.40,131.90,130.67,115.22,77.57,76.35,55.98.13 C NMR (126MHz, CDCl3 ) δ190.74, 162.40, 131.90, 130.67, 115.22, 77.57, 76.35, 55.98.
实施例12Example 12
所用的反应物为4-烯丙基醚苯甲醇(1.64g，10.0mmol，即式(I)中的R1为4-烯丙基醚，R2为氢，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：氯化铁(0.08g，0.5mmol)，4-甲氧基苯基甘氨酸(0.18g，1.0mmol)，TEMPO(0.16g，1.0mmol)，叔戊醇30.0mL，用氧气将反应瓶内的空气置换后回流搅拌12h。最终得到产物1.48g，收率91％。The reactant used is 4-allyl ether benzyl alcohol (1.64g, 10.0mmol, that is, R in formula (I ) is 4-allyl ether, R ishydrogen , X is carbon, n is 1, m is 0), the experimental method and steps are the same as in Example 1, the difference is: ferric chloride (0.08g, 0.5mmol), 4-methoxyphenylglycine (0.18g, 1.0mmol), TEMPO (0.16g , 1.0mmol), tert-amyl alcohol 30.0mL, the air in the reaction flask was replaced with oxygen, and then refluxed and stirred for 12h. Finally, 1.48 g of the product was obtained with a yield of 91%.
核磁共振氢谱1H NMR(500MHz,CDCl3)δ9.89(s,1H),7.84(d,J＝8.8Hz,2H),7.02(d,J＝8.7Hz,2H),6.06(ddd,J＝22.5,10.5,5.3Hz,1H),5.44(dd,J＝17.3,1.4Hz,1H),5.34(dd,J＝10.5,1.3Hz,1H),4.63(d,J＝5.3Hz,2H).1 H NMR (500MHz, CDCl3) δ9.89(s, 1H), 7.84(d, J=8.8Hz, 2H), 7.02(d, J=8.7Hz, 2H), 6.06(ddd, J =22.5,10.5,5.3Hz,1H),5.44(dd,J=17.3,1.4Hz,1H),5.34(dd,J=10.5,1.3Hz,1H),4.63(d,J=5.3Hz,2H) .
核磁共振碳谱13C NMR(126MHz,CDCl3)δ190.72,163.58,132.28,131.92,130.04,118.29,114.99,68.98.13 C NMR (126MHz, CDCl3) δ190.72, 163.58, 132.28, 131.92, 130.04, 118.29, 114.99, 68.98.
实施例13Example 13
所用的反应物为1-(4-甲基苯基)乙醇(13.62g，100.0mmol，即式(I)中的R1为4-甲基，R2为甲基，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：氯化亚铁(1.27g，10.0mmol)，4-氯苯基缬氨酸(2.28g，10.0mmol)，TEMPO(2.34g，15mmol)，间二甲苯300.0mL，用氧气将反应瓶内的空气置换后回流搅拌24h。最终得到产物12.34g，收率92％。The reactant used is 1-(4-methylphenyl)ethanol (13.62g, 100.0mmol, that is, R in formula (I ) is4 -methyl, R is methyl, X is carbon, and n is 1, m is 0), experimental method and step are with embodiment 1, difference is: ferrous chloride (1.27g, 10.0mmol), 4-chlorophenylvaline (2.28g, 10.0mmol), TEMPO (2.34g, 15mmol), m-xylene 300.0mL, replace the air in the reaction flask with oxygen, and then reflux and stir for 24h. Finally, 12.34 g of the product was obtained with a yield of 92%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ2.41(s,3H),2.57(s,3H),7.25(d,J＝4.0Hz,2H),7.86(d,J＝4.3Hz,2H).1 H NMR (500MHz, CDCl3 ): δ2.41(s, 3H), 2.57(s, 3H), 7.25(d, J=4.0Hz, 2H), 7.86(d, J=4.3Hz ,2H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ21.6,26.4,128.4,129.2,134.7,143.8,197.9.13 C NMR (125MHz, CDCl3 ): δ21.6, 26.4, 128.4, 129.2, 134.7, 143.8, 197.9.
实施例14Example 14
所用的反应物为1-(4-氟苯基)乙醇(1.40g，10.0mmol，即式(I)中的R1为4-氟，R2为甲基，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：三氟甲磺酸铁(0.50g，1.0mmol)，L-异亮氨酸(0.26g，2.0mmol)，TEMPO(0.16g，1.0mmol)，二甲苯30.0mL，用氧气将反应瓶内的空气置换后回流搅拌48h。最终得到产物1.23g，收率88％。The reactant used was 1-(4-fluorophenyl)ethanol (1.40 g, 10.0 mmol, that is, R in formula (I ) was4 -fluoro, R was methyl, X was carbon, n was 1, m is 0), the experimental method and steps are the same as in Example 1, the difference is: iron trifluoromethanesulfonate (0.50g, 1.0mmol), L-isoleucine (0.26g, 2.0mmol), TEMPO (0.16 g, 1.0mmol), xylene 30.0mL, reflux and stir for 48h after replacing the air in the reaction flask with oxygen. Finally, 1.23 g of the product was obtained with a yield of 88%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ2.59(s,3H),7.13(t,J＝9.0Hz,2H),7.96-8.00(q,2H).1 H NMR (500MHz, CDCl3 ): δ2.59(s, 3H), 7.13(t, J=9.0Hz, 2H), 7.96-8.00(q, 2H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ26.3,115.5,130.9,133.7,164.7,166.7,196.4.13 C NMR (125MHz, CDCl3 ): δ26.3, 115.5, 130.9, 133.7, 164.7, 166.7, 196.4.
实施例15Example 15
所用的反应物为1-(3-三氟甲基苯基)乙醇(1.90g，10.0mmol，即式(I)中的R1为3-三氟甲基，R2为甲基，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：三氟甲磺酸铁(0.50g，1.0mmol)，L-苯丙氨酸(0.02g，0.1mmol)，TEMPO(0.02g，0.1mmol)，叔戊醇30.0mL，用氧气将反应瓶内的空气置换后回流搅拌60h。最终得到产物1.54g，收率82％。The reactant used is 1-(3-trifluoromethylphenyl)ethanol (1.90g, 10.0mmol, that is, R in formula (I ) is3 -trifluoromethyl, R is methyl, X is Carbon, n is 1, m is 0), experimental method and step are with embodiment 1, difference is: iron trifluoromethanesulfonate (0.50g, 1.0mmol), L-phenylalanine (0.02g, 0.1 mmol), TEMPO (0.02 g, 0.1 mmol), 30.0 mL of tert-amyl alcohol, replaced the air in the reaction flask with oxygen and stirred at reflux for 60 h. Finally, 1.54 g of the product was obtained with a yield of 82%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ2.64(s,3H),7.61(t,J＝7.8Hz,1H),7.81(d,J＝7.5Hz,1H),8.13(d,J＝8.0Hz,1H),8.19(s,1H).1 H NMR (500MHz, CDCl3 ): δ2.64(s, 3H), 7.61(t, J=7.8Hz, 1H), 7.81(d, J=7.5Hz, 1H), 8.13(d ,J＝8.0Hz,1H),8.19(s,1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ26.4,124.7,125.0,129.2,129.5,131.1,131.4,137.5,196.6.13 C NMR (125MHz, CDCl3 ): δ26.4, 124.7, 125.0, 129.2, 129.5, 131.1, 131.4, 137.5, 196.6.
实施例16Example 16
所用的反应物为1-苯丙醇(1.36g，10.0mmol，即式(I)中的R1为4-氢，R2为乙基，X为碳，n为1，m为0)，实验方法和步骤同实施例1，不同之处在于：溴化铁(0.30g，1.0mmol)，2-甲基丙氨酸(0.05g，0.5mmol)，TEMPO(0.16g，1.0mmol)，二氧六环30.0mL，用氧气将反应瓶内的空气置换后回流搅拌48h。最终得到产物1.13g，收率84％。The reactant used is 1-phenylpropanol (1.36g, 10.0mmol, that is, R in formula (I ) is4 -hydrogen, R is ethyl, X is carbon, n is 1, and m is 0), Experimental method and step are with embodiment 1, and difference is: iron bromide (0.30g, 1.0mmol), 2-methylalanine (0.05g, 0.5mmol), TEMPO (0.16g, 1.0mmol), two Oxyhexane 30.0mL, replace the air in the reaction bottle with oxygen, and then reflux and stir for 48h. Finally, 1.13 g of the product was obtained with a yield of 84%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ1.18(t,J＝7.5Hz,3H),2.92-2.97(q,2H),7.40(t,J＝7.0Hz,2H),7.50(t,J＝7.5Hz,1H),7.92(d,J＝3.5Hz,2H).1 H NMR (500MHz, CDCl3 ): δ1.18(t, J=7.5Hz, 3H), 2.92-2.97(q, 2H), 7.40(t, J=7.0Hz, 2H), 7.50 (t,J=7.5Hz,1H),7.92(d,J=3.5Hz,2H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ8.0,31.5,127.8,128.3,132.6,136.8,200.4.13 C NMR (125MHz, CDCl3 ): δ8.0, 31.5, 127.8, 128.3, 132.6, 136.8, 200.4.
实施例17Example 17
所用的反应物为1-(2-噻吩)乙醇(1.28g，10.0mmol，即式(I)中的R1为4-氢，R2为甲基，X为硫，n为0，m为0)，实验方法和步骤同实施例1，不同之处在于：三氟甲磺酸亚铁(0.35g，1.0mmol)，L-缬氨酸(0.12g，1.0mmol)，TEMPO(0.32g，2.0mmol)，氯苯30.0mL，用氧气将反应瓶内的空气置换后回流搅拌36h。最终得到产物1.11g，收率88％。The reactant used is 1-(2-thiophene)ethanol (1.28g, 10.0mmol, that is, R in formula (I ) is4 -hydrogen, R is methyl, X is sulfur, n is 0, m is 0), experimental method and steps are the same as in Example 1, and the difference is: ferrous trifluoromethanesulfonate (0.35g, 1.0mmol), L-valine (0.12g, 1.0mmol), TEMPO (0.32g, 2.0mmol), 30.0mL of chlorobenzene, the air in the reaction flask was replaced with oxygen, and then refluxed and stirred for 36h. Finally, 1.11 g of the product was obtained with a yield of 88%.
核磁共振氢谱1H NMR(500MHz,CDCl3):δ2.49(t,J＝7.0Hz,3H),7.04-7.07(m,1H),7.55-7.59(m,1H),7.62-7.65(m,1H).1 H NMR (500MHz, CDCl3): δ2.49(t, J=7.0Hz, 3H), 7.04-7.07(m, 1H), 7.55-7.59(m, 1H), 7.62-7.65(m ,1H).
核磁共振碳谱13C NMR(125MHz,CDCl3):δ26.5,128.0,132.4,133.6,144.3,190.5.13 C NMR (125MHz, CDCl3 ): δ26.5, 128.0, 132.4, 133.6, 144.3, 190.5.
实施例18Example 18
所用的反应物为苄叉丙醇(1.48g，10.0mmol，即式(I)中R1为氢，R2为甲基，X为碳，n为1，m为1)，实验方法和步骤同实施例1，不同之处在于：氯化亚铁(0.13g，1.0mmol)，L-苯丙氨酸(0.17g，1.0mmol)，TEMPO(0.08g，0.5mmol)，三氟甲苯30.0mL，用氧气将反应瓶内的空气置换后回流搅拌36h。最终得到产物1.32g，收率90％。The reactant used is benzylidene propanol (1.48g, 10.0mmol, namely formula (I) in R1 is hydrogen, R2 is methyl, X is carbon, n is 1, m is 1), experimental method and step With embodiment 1, difference is: ferrous chloride (0.13g, 1.0mmol), L-phenylalanine (0.17g, 1.0mmol), TEMPO (0.08g, 0.5mmol), trifluorotoluene 30.0mL , Replace the air in the reaction bottle with oxygen and then reflux and stir for 36h. Finally, 1.32 g of the product was obtained with a yield of 90%.
核磁共振氢谱1H NMR(500MHz,CDCl3)δ7.59–7.48(m,3H),7.45–7.35(m,3H),6.72(d,J＝16.3Hz,1H),2.38(s,3H).1 H NMR (500MHz, CDCl3 ) δ7.59–7.48(m,3H),7.45–7.35(m,3H),6.72(d,J＝16.3Hz,1H),2.38(s,3H) ).
核磁共振碳谱13C NMR(126MHz,CDCl3)δ198.34,143.39,134.39,130.46,128.92,128.20,127.14,27.43.13 C NMR (126MHz, CDCl3 ) δ198.34, 143.39, 134.39, 130.46, 128.92, 128.20, 127.14, 27.43.
由上述的实施例表明，本发明所提供的常压下利用氧气作氧化剂，铁盐作催化剂，氨基酸作配体，TEMPO作助催化剂，回流条件下实现醇的有氧氧化制备醛/酮的方法，具有底物适用范围广、操作易于控制、成本低廉、反应过程对环境友好、无污染等特点。Shown by above-mentioned embodiment, under the atmospheric pressure provided by the present invention utilizes oxygen to make oxidant, iron salt is made catalyst, amino acid is made ligand, and TEMPO is made cocatalyst, realizes the method for preparing aldehyde/ketone by the aerobic oxidation of alcohol under reflux condition , which has the characteristics of wide application range of substrates, easy operation and control, low cost, environmental friendliness and no pollution in the reaction process.
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| CN201510594861.1ACN105294413B (en) | 2015-09-17 | 2015-09-17 | Method for preparing aldehyde/ketone by catalyzing alcohol oxidation with iron salt |
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| CN201510594861.1ACN105294413B (en) | 2015-09-17 | 2015-09-17 | Method for preparing aldehyde/ketone by catalyzing alcohol oxidation with iron salt |
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| CN106905097A (en)* | 2017-03-07 | 2017-06-30 | 浙江工业大学 | Method for preparing aldehyde by oxidizing primary alcohol |
| CN113968832B (en)* | 2021-10-19 | 2024-01-09 | 安徽金禾实业股份有限公司 | Preparation method of 2-acetyl furan |
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| US6426418B1 (en)* | 2001-11-02 | 2002-07-30 | Apotex, Inc. | Processes for the manufacturing of 3-hydroxy-N,1,6-trialkyl-4-oxo-1,4-dihydropyridine-2-carboxamide |
| CN103772082B (en)* | 2010-07-26 | 2016-01-20 | 华东师范大学 | The method of aldehydes or ketones prepared by a kind of dioxygen oxidation alcohol |
| CN102442973A (en)* | 2011-09-22 | 2012-05-09 | 华东理工大学 | Catalytic oxidation of primary alcohol ring-closing method for synthesizing benzimidazole and benzothiazole compounds |
| CN104557355A (en)* | 2014-12-27 | 2015-04-29 | 浙江工业大学 | Method for preparing aldehyde or ketone through promoting copper-catalyzed aqueous alcohol to oxidize by functionalized amino acid |
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