WO2023232002A1 - 一种铁催化的醇氧化酯化制备羧酸酯的方法 - Google Patents

一种铁催化的醇氧化酯化制备羧酸酯的方法 Download PDF

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WO2023232002A1
WO2023232002A1 PCT/CN2023/096993 CN2023096993W WO2023232002A1 WO 2023232002 A1 WO2023232002 A1 WO 2023232002A1 CN 2023096993 W CN2023096993 W CN 2023096993W WO 2023232002 A1 WO2023232002 A1 WO 2023232002A1
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mmol
group
nmr
tempo
reaction
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麻生明
于一博
钱辉
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Fudan University
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Definitions

  • the invention belongs to the technical field of chemical synthesis and relates to an iron-catalyzed method for preparing carboxylic acid ester compounds by direct oxidation and esterification of alcohol using oxygen or air as an oxidizing agent.
  • Carboxylate esters are widely found in bulk chemicals, fine chemicals, natural products and polymers (Otera, J. Esterification: Methods, Reactions, and Applications, Wiley-VCH, Weinheim, 2003.). Precisely because of their wide range of uses, the synthesis of ester compounds has also attracted much attention. Traditional methods generally involve nucleophilic substitution reactions between carboxylic acid derivatives (acyl halides, acid anhydrides, etc.) and alcohols, but these reactions often require harsh reaction conditions and produce chemically equivalent by-products (Otera, J. Chem. Rev.1993,93 1449.).
  • the invention overcomes the shortcomings of the prior art and provides a low-cost, suitable for industrial production, mild reaction conditions, simple operation, green iron-catalyzed method of preparing carboxylic acid ester compounds through alcohol oxidative esterification using oxygen or air as an oxidant. Methods.
  • the prior art there has been no report on the oxidative esterification of alcohol using oxygen or air as the oxidant in the Fe/TEMPO system.
  • the invention overcomes the shortcomings of the existing oxidation technology that uses equivalent or excessive amounts of oxidants or precious metals as catalysts, harsh reaction conditions, unavailable raw materials, and high costs, and provides a greener, cleaner, and more cost-effective method under atmospheric pressure conditions.
  • Cheap oxygen or air is used as an oxidant to achieve oxidative esterification of alcohol.
  • the reaction uses industrially available and cheap iron nitrate, nitrogen oxides, and Lewis acid as catalysts, and oxygen or air as the oxidant to successfully achieve the oxidative esterification of alcohol.
  • the invention has low cost, wide source of raw materials, green and clean reaction process, low cost, suitable for industrial production, mild reaction conditions, easy operation, environmental friendliness and other beneficial effects.
  • the invention provides an iron-catalyzed method for directly oxidizing and esterifying alcohols to prepare carboxylic acid ester compounds using oxygen or air as an oxidant.
  • two alcohols are used as The raw materials are ferric nitrate nonahydrate, nitrogen oxide and Lewis acid as catalysts, and oxygen or air is used as oxidant to directly oxidize and esterify the alcohol to generate carboxylic acid ester compounds.
  • the two alcohols are R 1 CH 2 OH and R 2 OH.
  • the reaction process is shown in reaction formula (1):
  • the R 1 includes an alkyl group, an alkyl group with a functional group, and a phenyl group with a functional group;
  • the functional groups in the alkyl group with functional groups are halogen, ether bond, ester group, cycloalkyl group, aryl group, heteroaryl, alkenyl, alkynyl, allenyl, alkynyl group with functional groups, amino group, etc.;
  • the aryl group is phenyl, halophenyl, alkylphenyl, alkoxyphenyl, alkoxynaphthyl, biphenyl, nitrophenyl, ester substituted phenyl, cyanophenyl , m-trifluoromethylphenyl, etc.
  • the heteroaryl group is thienyl, etc.;
  • the functional groups in the alkynyl group with functional groups are alkyl, phenyl, etc.;
  • the phenyl group with a functional group is an alkoxy group, nitro group, etc.
  • the R 2 OH is methanol or ethanol.
  • the R 1 includes a C1-C20 alkyl group, a C1-C20 alkyl group with a functional group;
  • the functional groups in the alkyl group with functional groups are fluorine, chlorine, bromine, iodine, ether bond, ester group, alkenyl group, alkynyl group, allenyl group, phenyl group, p-chlorophenyl group, alkylphenyl group, m- Methoxyphenyl, alkoxynaphthyl, biphenyl, p-nitrophenyl, p-cyanophenyl, ester-substituted phenyl, thienyl, amino.
  • R 1 includes a C3-C20 alkyl group, a C3-C20 alkyl group with a functional group
  • the R 1 CH 2 OH is stearyl alcohol, cetyl alcohol, dodecyl alcohol, 9-bromo-1-nonanol, 9-iodo-1-nonanol, 9-phenoxy-1-nonanol Alcohol, 6-ethoxy-1-hexanol, 8-(toluene-4-sulfonyloxy)-octanol, 6-(methanesulfonyl)-hexanol, (8-hydroxyoctyl)acetate, Benzoate-(6-hydroxyhexanoate), 6-hydroxyhexanoic acid methyl ester, 6-hydroxyhexanoic acid ethyl ester, 6-hydroxyhexanoic acid benzyl ester, 10-undecen-1-ol, 9-decene- 1-ol, 10-undecyn-1-ol, 7-octyn-1-ol, 6-octyn-1-ol, 7-phenyl
  • the nitrogen oxide is 2,2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO), 4-acetamido-2,2,6,6-tetramethylpiperidine Nitrogen oxide (4-NHAc-TEMPO), 4-methoxy-2,2,6,6-tetramethylpiperidine nitrogen oxide (4-OMe-TEMPO), 4-hydroxy-2,2,6 , one or more of 6-tetramethylpiperidine nitrogen oxide (4-OH-TEMPO), 9-azabicyclo[3.3.1]nonane-N-oxyl radical (ABNO), etc.; preferred Ground, the nitrogen oxide is 2,2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO), 4-methoxy-2,2,6,6-tetramethylpiperidine nitrogen oxide (4-OMe-TEMPO); further preferably, it is 2,2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO).
  • TEMPO 2,2,6,6-tetramethylpiperidine nitrogen oxide
  • 4-OMe-TEMPO 4-methoxy-2,2,6,6-tetramethylpipe
  • the Lewis acid is bismuth chloride, aluminum chloride, ferric chloride, indium chloride, indium bromide, bismuth bromide, tin chloride, copper fluoride, zinc chloride, trifluoromethyl One or more of ytterbium sulfonate, lanthanum triflate, scandium triflate, etc.; preferably, the Lewis acid is bismuth chloride, aluminum chloride; further preferably, it is bismuth chloride.
  • the organic solvent is dichloromethane, 1,2-dichloroethane, 1,1-dichloroethane, chloroform, toluene, acetonitrile, chloroform, ethyl acetate, 1,3- One or more mixtures of dichloropropane, 1,2-dichloropropane, nitromethane, ethylene glycol dimethyl ether, dioxane, etc.; preferably, the organic solvent is 1,2-dichloropropane. Ethyl chloride, toluene; further preferably, 1,2-dichloroethane.
  • the molar ratio of the raw material alcohol R 1 CH 2 OH and R 2 OH is 1: (1-8); preferably, the molar ratio of the raw material alcohol R 1 CH 2 OH and R 2 OH is It is 1: (4-5); further preferably, it is 1:5.
  • the molar ratio of the raw material alcohol R 1 CH 2 OH, iron nitrate nonahydrate, nitrogen oxides, and Lewis acid is 100: (1-10): (1-10): (1-11) ;
  • the molar ratio of the raw material alcohol R 1 CH 2 OH, iron nitrate nonahydrate, nitrogen oxides, and Lewis acid is 100: (6-8): 5:10; further preferably, it is 100:6 :5:10.
  • the reaction temperature is 25-60°C; preferably, the reaction temperature is 40-50°C; further preferably, the reaction temperature is 50°C.
  • the reaction time is 40-60 hours, preferably 48 hours.
  • the source of oxygen is pure oxygen or air.
  • the possible mechanism of the present invention is as follows: first, alcohol is oxidized under the combined action of iron nitrate, TEMPO and Lewis acid (such as BiCl 3 ) to obtain aldehyde; then, the aldehyde is attacked by methanol to form hemiacetal or acetal, and the acetal can Under the action of BiCl 3 , it returns to hemiacetal, and finally the hemiacetal is oxidized to obtain the corresponding methyl ester product.
  • Lewis acid such as BiCl 3
  • the present invention verified that aldehyde is an intermediate of the reaction of the present invention by monitoring the reaction, and the generation of acid was almost not monitored during the reaction process.
  • the monitoring reaction diagram is shown in Figure 1, which further proves that the reaction system of the present invention does not involve Generation of acid;
  • BiCl 3 or AlCl 3 etc. play the role of Lewis acid instead of acting as an ordinary inorganic chloride.
  • the essential innovations of the present invention are: (1) Starting from the catalytic system, the present invention uses a new catalytic system of iron nitrate, nitrogen oxides, and Lewis acid to directly oxidize and esterify two alcohols to obtain carboxylic acid ester compounds , which cannot obtain the corresponding carboxylic acid ester compounds under the previously reported catalytic systems of iron nitrate, nitrogen oxides, and inorganic halides. For details, see Comparative Example 1 of the present invention; (2) From the alcohol oxidative esterification Starting from the concept, the present invention proposes a convenient and simple method to achieve the oxidative esterification of two alcohols. However, most of the previously reported methods rely on the use of precious metals, such as Au, Pd, etc., which greatly increases the production cost, and Not only is the iron/TEMPO system cheaper, it has not been reported before.
  • the beneficial effects of the present invention include:
  • the present invention discloses that under the conditions of 25-60°C, in an organic solvent, using R 1 CH 2 OH and R 2 OH as raw materials, in the presence of iron nitrate nonahydrate, nitrogen oxides and Lewis acid As a catalyst, oxygen or air is used as the oxidant to directly oxidize and esterify the alcohol to generate carboxylic acid ester compounds.
  • the present invention uses oxygen or air as the oxidant to oxidize and esterify primary alcohols containing various functional groups (such as halogen, ether bonds, ester groups, alkenyl groups, alkynyl groups, etc.) to obtain carboxylic acid ester compounds.
  • the substrate of the present invention has wide applicability and high yield, and uses cheap and green iron nitrate, TEMPO, and bismuth chloride as catalysts, and abundant and easily available oxygen or air as the oxidant, effectively solving the problem of substrates in the current method. It has narrow universality, requires the participation of precious metals, and uses equivalent or excessive amounts of toxic oxidants.
  • the method is simple to operate, the catalyst and raw materials are cheap and easy to obtain, the reaction conditions are mild, the yield is excellent, the substrate functional group has good compatibility, the reaction scale can be enlarged, the reaction process is environmentally friendly, and there is no pollution, and many other advantages.
  • the method of the invention can be used for both small-scale laboratory synthesis and large-scale industrial production.
  • the invention uses oxygen or air, a green, cheap, widely sourced clean energy source, to replace the chemical oxidant required in the traditional oxidation method as the oxidant.
  • the by-product is water.
  • the entire reaction process will hardly cause any pollution to the environment, and is in line with green chemistry. requirements.
  • the ferric nitrate nonahydrate, nitrogen oxides and Lewis acid used in the method of the present invention are all commercially available reagents with low prices and high yields, and can effectively reduce Cost of production.
  • the reaction conditions of the invention are mild and the post-processing is simple, so the operation is convenient and easy to control.
  • Figure 1 is a monitoring reaction diagram of the present invention.
  • mol in the reaction formulas of the following examples represents mole; Fe(NO 3 ) 3 ⁇ 9H 2 O represents iron (III) nitrate nonahydrate; TEMPO represents 2,2,6,6-tetramethylpiperidine oxide; BiCl 3 represents bismuth chloride; DCE represents 1,2-dichloroethane; Et 2 O represents diethyl ether; DCM represents dichloromethane; CHCl 3 represents chloroform; toluene represents toluene; dioxane represents 1,4-dioxane; O 2 balloon means that the reaction is carried out in an oxygen atmosphere provided by an oxygen balloon; Air balloon means that the reaction is carried out in an air atmosphere provided by an air balloon; h means hours; the boiling range of petroleum ether is 60-90°C; the nuclear magnetic yield is determined by 1 H NMR It is confirmed that the internal standard is dibromomethane and the silica gel mesh number is 300-400.
  • Step 1 Add Fe(NO 3 ) 3 ⁇ 9H 2 O (24.3 mg, 0.06 mmol), TEMPO (8.4 mg, 0.05 mmol), BiCl 3 (31.3 mg, 0.1 mmol), and 1a to a 50 mL round-bottomed flask in sequence. (241.4 mg, 1.0 mmol), MeOH (202 ⁇ L, 5 mmol) and DCE (3 mL). An oxygen balloon was inserted and the reaction was stirred in a 50°C oil bath for 48 hours. The reaction solution was passed through a short silica gel column (3cm), eluted with diethyl ether (3 x 25mL), and the solvent was removed by rotary evaporation.
  • Step II Add Fe(NO 3 ) 3 ⁇ 9H 2 O (32.6mg, 0.08mmol), TEMPO (8.1mg, 0.05mmol), BiCl 3 (31.8mg, 0.1mmol), 1f to a 50mL round-bottomed flask in sequence. (146.0 mg, 1.0 mmol), MeOH (202 ⁇ L, 5 mmol) and DCE (3 mL). An oxygen balloon was inserted and the reaction was stirred in a 50°C oil bath for 48 hours. The reaction solution was passed through a short silica gel column (3cm), eluted with diethyl ether (3 x 25mL), and the solvent was removed by rotary evaporation.
  • Step III Add Fe(NO 3 ) 3 ⁇ 9H 2 O (24.5 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl 3 (31.9 mg, 0.1 mmol), 1 g in sequence to a 50 mL round-bottomed flask. (236.7 mg, 1.0 mmol), MeOH (202 ⁇ L, 5 mmol) and DCE (3 mL). An oxygen balloon was inserted and the reaction was stirred in a 50°C oil bath for 48 hours. The reaction solution was passed through a short silica gel column (3cm), eluted with diethyl ether (3 x 25mL), and the solvent was evaporated to remove the solvent.
  • the present invention explores the influence of alcohols on reaction products. It is found that methanol has the best effect. Ethanol and n-propanol can produce corresponding esterification products, but the efficiency is very low. The target product 5 cannot be obtained by reacting with other alcohols. See Table 1 for details.

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Abstract

本发明公开了一种铁催化的以氧气或空气作为氧化剂，醇直接氧化酯化制备羧酸酯类化合物的方法，所述方法为在25℃-60℃条件下，在有机溶剂中，以硝酸铁(Fe(NO3)3·9H2O)、氮氧化物和Lewis酸为催化剂，以氧气或空气作为氧化剂，醇直接氧化酯化生成羧酸酯类化合物。本发明操作简单，催化剂和原料廉价易得，反应条件温和，产率优秀，底物官能团兼容性较好，且反应规模可放大，反应过程对环境友好，不存在污染等诸多优点，具有工业化应用前景。

Description

一种铁催化的醇氧化酯化制备羧酸酯的方法 技术领域
本发明属于化学合成技术领域，涉及一种铁催化的以氧气或空气作为氧化剂，醇直接氧化酯化制备羧酸酯化合物的方法。
背景技术
羧酸酯广泛存在于大宗化学品、精细化学品、天然产物以及聚合物中(Otera,J.Esterification:Methods,Reactions,and Applications,Wiley-VCH,Weinheim,2003.)。也正是由于它们用途广泛，关于酯类化合物的合成也备受关注。传统的方法一般是羧酸衍生物(酰卤，酸酐等)与醇发生亲核取代反应，但这些反应往往需要比较严苛的反应条件以及会产生化学当量的副产物(Otera,J.Chem.Rev.1993,93 1449.)。近些年来，从醛出发与醇发生氧化酯化反应也有大量的报道，但是目前该路径仍需化学当量的氧化剂，如MnO2(Ekoue-Kovi,K.；Wolf,C.Chem.Eur.J.2008,14,6302.)，oxone(Travis,B.R.；Sivakumar,M.；Hollist,G.O.；Borhan,B.Org.Lett.2003,5,1031；Hackbusch,S.；Franz,A.H.Tetrahedron Lett.2016,57,2873.)，H2O2(Samanta,S.；Pappula,V.；Dinda,M.；Adimurthy,S.Org.Biomol.Chem.2014,12,9453；Gopinath,R.；Patel,B.K.Org.Lett.2000,2,577.)，TBHP(Zhu,Y.；Yan,H.；Lu,L.；Liu,D.；Ron,G.；Mao,J.J.Org.Chem.2013,78,9898；Guggilapu,S.D.；Prajapti,S.K.；Babu,B.N.Tetrahedron Lett.2015,56,889.)，TCCA(Gaspa,S.；Porcheddu,A.；De Luca,L.Org.Lett.2015,17,3666.)等，会对环境造成一定的负担，而且反应所需的醛往往是通过醇的选择性氧化得到。从绿色和可持续发展的角度来看，氧气是一种廉价易得、含量丰富、环境友好的氧化剂，因此目前利用氧气作为氧化剂吸引了人们的广泛兴趣(Arends,I.W.C.E.；Sheldon,R.A.Modern Oxidation Methods,Wiley-VCH,Weinheim,2004,pp.83；Mallat,T.；Baiker,A.Chem.Rev.2004,104,3037；Markó,I.E.；Giles,P.R.；Tsukazaki,M.；Chellé-Regnaut,I.；Gautier,A.；Dumeunier,R.；Philippart,F.；Doda,K.；Mutonkole,J.-L.；Brown,S.M.；Urch,C.J.Adv.Inorg.Chem.2004,56,211；Zhan,B.Z.；Thompson,A.；Tetrahedron 2004,60,2917；Schultz,M.J.；Sigman,M.S.Tetrahedron 2006,62,8227；Matsumoto,T.；Ueno,M.；Wang,N.；Kobayashi,S.Chem.Asian J.2008,3,196；Parmeggiani,C.；Cardona,F.Green Chem.2012,14, 547.)。因此，以氧气作为氧化剂，醇的直接氧化酯化被认为是一种理想的合成酯类化合物的方法。然而，要想实现上述反应，目前还依赖于贵金属的使用等(Shi,Z.；Zhang,C.；Tang,C.；Jiao,N.Chem.Soc.Rev.2012,41,3381.)。铁作为地壳中含量最丰富的金属，被广泛应用于催化各类反应，尤其在氧化反应中表现优秀。而TEMPO作为一类稳定的氮氧自由基，在于Fe或者Cu共催化氧化醇的反应中，表现出其独特的反应活性。但在Fe/TEMPO体系，以氧气或空气为氧化剂，醇的氧化酯化还未见报道。
发明内容
本发明克服了现有技术的不足，提供了一种成本低廉、适合工业化生产、反应条件温和、操作简便、绿色的铁催化的以氧气或空气为氧化剂，醇氧化酯化制备羧酸酯类化合物的方法。现有技术中关于Fe/TEMPO体系，以氧气或空气为氧化剂，醇的氧化酯化还未见报道。
本发明克服了现有氧化技术中使用当量或过量的氧化剂或贵金属作为催化剂，反应条件严苛、原料不可得、成本昂贵等缺陷，提供了一种在大气压的条件下，利用更加绿色、清洁、廉价的氧气或空气作为氧化剂，来实现醇的氧化酯化。反应以工业易得、廉价的硝酸铁、氮氧化物、Lewis酸为催化剂，氧气或空气作为氧化剂，成功实现了醇的氧化酯化。本发明所需成本低廉、原料来源广泛、反应过程绿色干净，具有成本低廉、适合工业化生产、反应条件温和、操作简便、对环境友好等有益效果。
本发明提供了一种铁催化的以氧气或空气作为氧化剂，醇直接氧化酯化制备羧酸酯类化合物的方法，在25℃-60℃的条件下，在有机溶剂中，以两种醇为原料，以九水合硝酸铁、氮氧化物和Lewis酸为催化剂，以氧气或空气作为氧化剂，将所述醇直接氧化酯化生成羧酸酯类化合物。在具体实施方案中，所述两种醇为R1CH2OH和R2OH。其反应过程如反应式(1)所示：
其中，
所述R1包括烷基，带有官能团的烷基，带有官能团的苯基；
所述带有官能团的烷基中的官能团为卤素、醚键、酯基、环烷基、芳基、杂芳基、烯基、炔基、联烯基、带官能团的炔基、氨基等；所述芳基为苯基、卤代苯基、烷基苯基、烷氧基苯基、烷氧基萘基、联苯基、硝基苯基、酯基取代的苯基、氰基苯基、间三氟甲基苯基等；所述杂芳基为噻吩基等；
所述带有官能团的炔基中的官能团为烷基、苯基等；
所述带有官能团的苯基为烷氧基、硝基等；
所述R2OH为甲醇或乙醇。
优选地，所述R1包括C1-C20的烷基，带有官能团的C1-C20的烷基；
所述带有官能团的烷基中的官能团为氟、氯、溴、碘、醚键、酯基、烯基、炔基、联烯基、苯基、对氯苯基、烷基苯基、间甲氧基苯基、烷氧基萘基、联苯基、对硝基苯基、对氰基苯基、酯基取代的苯基、噻吩基、氨基。
进一步优选地，R1包括C3-C20的烷基，带有官能团的C3-C20的烷基；
具体地，所述R1CH2OH为十八醇，十六醇，十二醇，9-溴-1-壬醇，9-碘-1-壬醇，9-苯氧基-1-壬醇，6-乙氧基-1-己醇，8-(甲苯-4-磺酰氧基)-辛醇，6-(甲磺酰基)-己醇，乙酸-(8-羟基辛)酯，苯甲酸-(6-羟基己)酯，6-羟基己酸甲酯，6-羟基己酸乙酯，6-羟基己酸苄酯，10-十一烯-1-醇，9-癸烯-1-醇，10-十一炔-1-醇，7-辛炔-1-醇，6-辛炔-1-醇，7-苯基-6-辛炔-1-醇，8-(丙基-2-炔-1-氧基)-辛醇，4-(((6-羟基乙基)氧)甲基)苯甲腈，2-(9-羟基壬基)异二氢吲哚-1,3-二酮，3-环已基-1-丙醇，苯己醇，苯戊醇，苯丁醇，苯丙醇，对氰基苯丙醇，对硝基苯丙醇，3-三氟甲基苯丙醇，对氯苯丙醇，对甲氧基苯丙醇，对硝基苯甲醇，对甲氧基苯甲醇，3-溴苯乙醇，2-苯基丙醇，噻吩-2-乙醇，金刚烷甲醇，肉桂醇，4-羟乙基联苯，6,7-二烯-1-辛醇。
本发明方法中，所述的氮氧化物为2,2,6,6-四甲基哌啶氮氧化物(TEMPO)、4-乙酰氨基-2,2,6,6-四甲基哌啶氮氧化物(4-NHAc-TEMPO)、4-甲氧基-2,2,6,6-四甲基哌啶氮氧化物(4-OMe-TEMPO)、4-羟基-2,2,6,6-四甲基哌啶氮氧化物(4-OH-TEMPO)、9-氮杂双环[3.3.1]壬烷-N-氧基自由基(ABNO)等之一种或几种；优选地，所述氮氧化物为2,2,6,6-四甲基哌啶氮氧化物(TEMPO)、4-甲氧基-2,2,6,6-四甲基哌啶氮氧化物(4-OMe-TEMPO)；进一步优选地，为2,2,6,6-四甲基哌啶氮氧化物(TEMPO)。
本发明方法中，所述的Lewis酸为氯化铋、氯化铝、氯化铁、氯化铟、溴化铟、溴化铋、氯化锡、氟化铜、氯化锌、三氟甲磺酸镱、三氟甲磺酸镧、三氟甲磺酸钪等之一种或几种；优选地，所述Lewis酸为氯化铋、氯化铝；进一步优选地，为氯化铋。
本发明方法中，所述有机溶剂为二氯甲烷、1,2-二氯乙烷、1,1-二氯乙烷、三氯甲烷、甲苯、乙腈、氯仿、乙酸乙酯、1,3-二氯丙烷、1,2-二氯丙烷、硝基甲烷、乙二醇二甲醚、二氧六环等中的一种或多种混合；优选地，所述有机溶剂为1,2-二氯乙烷、甲苯；进一步优选地，为1,2-二氯乙烷。
本发明方法中，所述的原料醇R1CH2OH与R2OH的摩尔比例为1：(1-8)；优选地，所述原料醇R1CH2OH与R2OH的摩尔比例为1：(4-5)；进一步优选地，为1:5。
本发明方法中，所述的原料醇R1CH2OH、九水合硝酸铁、氮氧化物、Lewis酸的摩尔比例为100：(1-10)：(1-10)：(1-11)；优选地，所述的原料醇R1CH2OH、九水合硝酸铁、氮氧化物、Lewis酸的摩尔比例为100：(6-8)：5：10；进一步优选地，为100:6:5:10。
本发明中，所述反应温度为25-60℃；优选地，反应温度为40-50℃；进一步优选地，反应温度为50℃。
本发明中，所述反应的时间为40-60小时，优选地，为48小时。
本发明中，所述氧气的来源为纯的氧气或空气。
本发明可能的机理如下：首先，醇在硝酸铁，TEMPO和Lewis酸(如BiCl3)的共同作用下，被氧化得到醛；然后，醛被甲醇进攻形成半缩醛或缩醛，缩醛可以在BiCl3的作用下回到半缩醛，最后半缩醛被氧化得到相应的甲酯产物，反应机理如下式(2)所示。
本发明通过监测反应验证了醛是本发明所述反应的中间体，而在反应过程中几乎未监测到酸的生成，监测反应图如图1所示，进一步证明本发明反应体系中并不涉及酸的生成；另外，在本发明反应体系中，BiCl3或AlCl3等起到Lewis酸的作用，而不是作为普通的无机氯化物。
本发明的实质创新点在于：(1)从催化体系出发，本发明利用硝酸铁、氮氧化物、Lewis酸这一新的催化体系，使得两种醇直接发生氧化酯化得到羧酸酯类化合物，这在之前报道的硝酸铁、氮氧化物、无机卤化物的催化体系下是不能得到相应的羧酸酯类化合物的，具体见本发明对比例1；(2)从醇氧化酯化这一概念出发，本发明提出了一种方便简单的方法能够实现两种醇的氧化酯化，而之前报道的方法大多依赖于贵金属的试用，如Au，Pd等，这极大提高了生产成本，而铁/TEMPO这一体系不仅更为廉价，而且关于这一体系之前尚未报道。
本发明的有益效果包括：本发明公开了在25-60℃的条件下，在有机溶剂中，以R1CH2OH和R2OH为原料，在九水合硝酸铁、氮氧化物和Lewis酸为催化剂，以氧气或空气作为氧化剂，将所述醇直接氧化酯化生成羧酸酯类化合物。本发明利用氧气或空气作为氧化剂，可将含有多种官能团(如卤素、醚键、酯基、烯基、炔基等)的一级醇氧化酯化得到羧酸酯类化合物。本发明底物普适性广泛，产率较高，并且使用了廉价绿色的硝酸铁，TEMPO，氯化铋作为催化剂，储量丰富易得的氧气或空气作为氧化剂，有效解决了当前方法中底物普适性窄，需要贵金属参与，当量或过量有毒氧化剂的使用等问题。本发明操作简单，催化剂和原料廉价易得，反应条件温和，产率优秀，底物官能团兼容性较好，且反应规模可放大，反应过程对环境友好，不存在污染等诸多优点。本发明方法既可用于小规模实验室合成，也可用于大规模工业生产。
本发明利用绿色，廉价，来源广泛的清洁能源氧气或空气替代传统氧化方法中所需要的化学氧化剂作为氧化剂，其副产物为水，整个反应过程中几乎不会对环境产生任何污染，符合绿色化学的要求。本发明方法中用到的九水合硝酸铁、氮氧化物和Lewis酸均为市售可得试剂，并且价格低廉，产率较高，可有效降低 生产成本。本发明反应条件温和，后处理简单，因此操作方便且易控制。
附图说明
图1为本发明监测反应图。
具体实施方式
结合以下具体实施例，对本发明作进一步的详细说明。实施本发明的过程、条件、实验方法等，除以下专门提及的内容之外，均为本领域的普遍知识和公知常识，本发明没有特别限制内容。
注：以下实施例反应式中的mol表示摩尔；Fe(NO3)3·9H2O表示九水合硝酸铁(III)；TEMPO表示2,2,6,6-四甲基哌啶氧化物；BiCl3表示氯化铋；DCE表示1,2-二氯乙烷；Et2O表示乙醚；DCM表示二氯甲烷；CHCl3表示氯仿；toluene表示甲苯；dioxane表示1,4-二氧六环；O2 balloon表示反应在氧气球提供的氧气氛围下进行；Air balloon表示反应在空气球提供的空气氛围下进行；h表示小时；石油醚沸程为60-90℃；核磁产率由1H NMR确定，内标为二溴甲烷，硅胶目数为300-400。
实施例1
步骤I：向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.3mg,0.06mmol)，TEMPO(8.4mg,0.05mmol)，BiCl3(31.3mg,0.1mmol)，1a(241.4mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，粗产品中加入2mL甲醇，1mL饱和亚硫酸氢钠溶液，剧烈搅拌1h，加无水硫酸钠干燥，过硅胶短柱(1cm)，DCM洗脱(3 x 15mL)，旋蒸旋去溶剂，利用硅胶柱层析法进行分离纯化(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后2/1)，得到产物淡黄色固体5a(188.0mg,70％)。
1H NMR(400MHz,CDCl3):δ＝3.66(s,3H,OCH3),2.30(t,J＝7.4Hz,2H,CH2),1.67-1.56(m,2H,CH2),1.34-1.17(m,24H,12 x CH2),0.88(t,J＝6.6Hz,3H,CH3)；13C NMR(100MHz,CDCl3):δ＝174.3,51.4,34.1,31.9,29.7,29.63,29.57, 29.4,29.3,29.2,29.1,24.9,22.7,14.1；IR(neat):v＝2950,2916,2849,1739,1465,1436,1377,1195,1164cm-1；MS(70eV,EI)m/z(％):270(M+,19.23),74(100).
实施例2
操作同本发明实施例1步骤I，1b(270.5mg,1.0mmol)，Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到白色固体5b(217.8mg,73％)(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后2/1)。
m.p.42.1-43.5℃(低熔点固体，无法重结晶，直接测熔点)；1H NMR(400MHz,CDCl3)δ＝3.66(s,3H,OCH3),2.30(d,J＝7.6Hz,2H,CH2),1.65-1.58(m,2H,CH2),1.32-1.17(m,28H,14 x CH2),0.88(t,J＝6.4Hz,3H,CH3)；13C NMR(100MHz,CDCl3)δ＝174.3,51.3,34.1,31.9,29.7,29.6,29.4,29.3,29.2,29.1,24.9,22.7,14.1；IR(neat):v＝2916,2848,1738,1463,1435,1380,1331,1254,1213,1194,1169,1105cm-1；MS(70eV,EI)m/z(％):298(M+,43.97),74(100).
实施例3
操作同本发明实施例1步骤I，1c(186.4mg,1.0mmol)，Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5c(160.7mg,75％)(洗脱剂：石油醚/乙酸乙酯＝20/1)。
1H NMR(400MHz,CDCl3)δ＝3.67(s,3H,OCH3),2.30(t,J＝7.6Hz,2H,CH2),1.70-1.57(m,2H,CH2),1.45-1.15(m,16H,CH2×8),0.88(t,J＝6.6Hz,3H,CH3)；13C NMR(100MHz,CDCl3)δ＝174.2,51.3,34.1,31.9,29.7,29.6,29.4,29.3,29.2,29.1,24.9,22.6,14.0；IR(neat):v＝2924,2855,1742,1463,1438,1363,1236,1198,1171,1116cm-1；MS(70eV,EI)m/z(％):214(M+,4.71),74(100).
实施例4
操作同本发明实施例1步骤I，1d(223.5mg,1.0mmol)，Fe(NO3)3·9H2O(32.3mg,0.08mmol)，TEMPO(8.3mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5d(189.5mg,74％,98％purity)(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后2/1)。
1H NMR(400MHz,CDCl3):δ＝3.66(s,3H,OCH3),3.40(t,J＝6.8Hz,2H,CH2),2.30(t,J＝7.4Hz,2H,CH2),1.85(quint,J＝7.1Hz,2H,CH2),1.68-1.56(m,2H,CH2),1.48-1.37(m,2H,CH2),1.32(s,6H,3 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.0,51.3,33.9,33.7,32.7,28.91,28.87,28.4,28.0,24.7；IR(neat):v＝2930,2855,1737,1458,1437,1362,1197,1170cm-1；MS(ESI)m/z:275(M(81Br)+Na)+,273(M(79Br)+Na)+.
实施例5
操作同本发明实施例1步骤I，1e(269.9mg,1.0mmol)，Fe(NO3)3·9H2O(32.3mg,0.08mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(32.1mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5e(200.1mg and 23.2mg(90％purity),74％)(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后3/1)。
1H NMR(400MHz,CDCl3):δ＝3.67(s,3H,OCH3),3.18(t,J＝7.0Hz,2H,CH2),2.30(t,J＝7.6Hz,2H,CH2),1.82(quint,J＝7.1Hz,2H,CH2),1.68-1.56(m,2H,CH2),1.45-1.35(m,2H,CH2),1.31(s,6H,3 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.1,51.4,34.0,33.4,30.3,28.9,28.2,24.8,7.1；IR(neat):v＝2926,2853,1736,1459,1434,1361,1195,1169cm-1；MS(ESI)m/z:299(M+H)+,321(M+Na)+.
实施例6
步骤II：向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(32.6mg,0.08mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，1f(146.0mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，粗产品中加入2mL THF，0.5mL HCl(3M),剧烈搅拌2h。加饱和碳酸氢钠溶液将反应液pH调节至8左右，加2mL饱和亚硫酸氢钠溶液，剧烈搅拌2h，反应液DCM萃取(3 x 15mL)，合并有机相，饱和食盐水洗，无水硫酸钠干燥，过滤，旋蒸旋去溶剂，利用硅胶柱层析法进行分离纯化(洗脱剂：石油醚/乙酸乙酯＝20/1至10/1)，得到产物淡黄色液体5f(88.6mg,49％,96％purity)。
1H NMR(400MHz,CDCl3):δ＝3.66(s,3H,OCH3),3.46(q,J＝6.9Hz,2H,OCH2),3.41(t,J＝6.6Hz,2H,OCH2),2.32(t,J＝7.6Hz,2H,CH2),1.73-1.52(m,4H,2 x CH2),1.46-1.32(m,2H,CH2),1.19(t,J＝7.0Hz,3H,CH3)；13C NMR(100MHz,CDCl3):δ＝174.0,70.2,66.0,51.3,33.9,29.3,25.7,24.7,15.0；IR(neat):v＝2975,2940,2860,1738,1437,1376,1201,1167,1109cm-1；MS(ESI)m/z:175(M+H)+,197(M+Na)+；HRMS calcd m/z for C9H19O3[M+H]+:175.1329,found 175.1330.
实施例7
步骤III：向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(31.9mg,0.1mmol)，1g(236.7mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，粗产品利用硅胶柱层析法进行分离纯化(洗脱剂：第一次过柱：石油醚/乙酸乙酯＝40/1；不纯部分二次过柱：石油醚/乙酸乙酯＝50/1)，得到产物淡黄色液体5g (166.4mg,63％)。
1H NMR(400MHz,CDCl3):δ＝7.32-7.20(m,2H,Ar-H),6.96-6.83(m,3H,Ar-H),3.93(t,J＝6.6Hz,2H,OCH2),3.65(s,3H,OCH3),2.29(t,J＝7.6Hz,2H,CH2),1.76(quint,J＝7.0Hz,2H,CH2),1.62(quint,J＝7.3Hz,2H,CH2),1.52-1.40(m,2H,CH2),1.38-1.27(m,6H,3 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.1,159.0,129.3,120.3,114.4,67.7,51.3,33.9,29.2,29.1,29.0,25.9,24.8；IR(neat):v＝2930,2856,1737,1599,1496,1470,1436,1242,1198,1169cm-1；MS(ESI)m/z:265(M+H)+,287(M+Na)+；HRMS calcd m/z for C16H25O3[M+H]+:265.1798,found 265.1796.
实施例8
操作同本发明实施例6步骤II，1h(196.7mg,1.0mmol)，Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.2mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5h(106.3mg,47％)(洗脱剂：石油醚/乙酸乙酯＝3/1至2/1)。
1H NMR(400MHz,CDCl3):δ＝4.23(t,J＝6.4Hz,2H,OCH2),3.67(s,3H,OCH3),3.01(s,3H,CH3),2.34(t,J＝7.4Hz,2H,CH2),1.82-1.73(m,2H,CH2),1.72-1.62(m,2H,CH2),1.50-1.39(m,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.7,69.6,51.4,37.1,33.5,28.6,24.8,24.1；IR(neat):v＝2935,2859,1732,1438,1349,1169,1104cm-1；MS(ESI)m/z:225(M+H)+,247(M+Na)+.
实施例9
操作同本发明实施例1步骤I，1i(300.5mg,1.0mmol)，Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(8.4mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5i(230.1mg,70％)(洗 脱剂：石油醚/乙酸乙酯＝15/1至10/1)。
1H NMR(400MHz,CDCl3):δ＝7.79(d,J＝8.0Hz,2H,Ar-H),7.35(d,J＝7.6Hz,2H,Ar-H),4.01(d,J＝6.4Hz,2H,CH2),3.66(s,3H,OCH3),2.45(s,3H,CH3),2.28(d,J＝7.6Hz,2H,CH2),1.68-1.50(m,4H,2 x CH2),1.34-1.18(m,6H,3 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.0,144.6,133.2,129.7,127.8,70.5,51.3,33.8,28.7,28.6,28.4,25.0,24.6,21.5；IR(neat):v＝2939,2910,2868,1731,1598,1466,1434,1347,1311,1248,1215,1173,1098,1071,1048cm-1；MS(70eV,EI)m/z(％):328(M+,7.42),91(100)；HRMS calcd m/z for C16H24O5S[M]+:328.1339,Found:328.1339.
实施例10
操作同本发明实施例6步骤II，1j(189.1mg,1.0mmol)，Fe(NO3)3·9H2O(24.3mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5j(144.7mg,67％)(洗脱剂：石油醚/乙酸乙酯＝15/1至10/1)。
1H NMR(400MHz,CDCl3):δ＝4.05(t,J＝6.8Hz,2H,OCH2),3.67(s,3H,OCH3),2.31(t,J＝7.4Hz,2H,CH2),2.04(s,3H,CH3),1.70-1.56(m,4H,2 x CH2),1.43-1.28(m,6H,3 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.0,171.0,64.3,51.3,33.8,28.8,28.7,28.4,25.6,24.7,20.8；IR(neat):v＝2937,2858,1735,1437,1365,1234,1170,1034cm-1；MS(ESI)m/z:217(M+H)+,239(M+Na)+；HRMS calcd m/z for C11H21O4[M+H]+:217.1434,found 217.1429.
实施例11
操作同本发明实施例6步骤II，1k(220.1mg,1.0mmol)，Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(31.0mg,0.1mmol)，MeOH (202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5k(164.3mg,66％)(洗脱剂：石油醚/乙酸乙酯＝20/1)。
1H NMR(400MHz,CDCl3):δ＝8.04(d,J＝7.2Hz,2H,Ar-H),7.54(t,J＝7.4Hz,1H,Ar-H),7.43(t,J＝7.6Hz,2H,Ar-H),4.32(t,J＝6.6Hz,2H,OCH2),3.66(s,3H,OCH3),2.34(t,J＝7.4Hz,2H,CH2),1.79(quint,J＝7.1Hz,2H,CH2),1.71(quint,J＝7.7Hz,2H,CH2),1.54-1.42(m,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.7,166.4,132.7,130.2,129.3,128.2,64.5,51.3,33.7,28.2,25.4,24.4；IR(neat):v＝2951,1735,1715,1451,1436,1271,1171,1114cm-1；MS(70eV,EI)m/z(％):250(M+,1.09),105(100)；HRMS calcd m/z for C14H18O4[M]+:250.1200,Found:250.1204.
实施例12
操作同本发明实施例1步骤I，1l(146.3mg,1.0mmol)，Fe(NO3)3·9H2O(24.4mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5l(116.3mg,67％)(洗脱剂：石油醚/二氯甲烷＝2/1至1/1，然后二氯甲烷)。
1H NMR(400MHz,CDCl3):δ＝3.56(s,6H,2 x OCH3),2.27-2.13(m,4H,2 x CH2),1.60-1.47(m,4H,2 x CH2)；13C NMR(100MHz,CDCl3)δ＝173.7,51.5,33.6,24.3；IR(neat)v＝2955,1734,1437,1367,1248,1197,1171,1083cm-1；MS(70eV,EI)m/z(％):143((M-OMe)+,73.02),114(100).
实施例13
操作同本发明实施例6步骤II，1m(160.7mg,1.0mmol)，Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(32.0mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5m(110.3mg,58％)(洗 脱剂：石油醚/乙酸乙酯＝20/1至10/1)。
1H NMR(400MHz,CDCl3):δ＝4.13(q,J＝7.1Hz,2H,OCH2),3.67(s,3H,OCH3),2.40-2.26(m,4H,2 x CH2),1.73-1.58(m,4H,2 x CH2),1.26(t,J＝7.2Hz,3H,CH3)；13C NMR(100MHz,CDCl3):δ＝173.7,173.2,60.2,51.4,33.8,33.5,24.3,24.2,14.1；IR(neat):v＝2981,2945,2873,1731,1438,1372,1242,1172,1143cm-1；MS(ESI)m/z:189(M+H)+,211(M+Na)+.
实施例14
操作同本发明实施例6步骤II，1n(223.8mg,1.0mmol)，Fe(NO3)3·9H2O(32.3mg,0.08mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5n(157.9mg,63％)(洗脱剂：石油醚/乙酸乙酯＝25/1至20/1)。
1H NMR(400MHz,CDCl3):δ＝7.44-7.25(m,5H,Ar-H),5.11(s,2H,OCH2),3.65(s,3H,OCH3),2.37(t,J＝7.0Hz,2H,CH2),2.32(t,J＝7.0Hz,2H,CH2),1.76-1.58(m,4H,2 x CH2)；13C NMR(100MHz,CDCl3):δ＝173.6,173.0,135.9,128.4,128.1,66.0,51.4,33.7,33.5,24.2；IR(neat):v＝2951,1731,1455,1438,1381,1358,1164,1140cm-1；MS(ESI)m/z:251(M+H)+,273(M+Na)+.
实施例15
操作同本发明实施例6步骤II，1o(165.1mg,95％purity,1.0mmol)，Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.5mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5o(118.6mg,63％,98％purity)(洗脱剂：石油醚/乙酸乙酯＝60/1至50/1)。
1H NMR(400MHz,CDCl3):δ＝5.87-5.73(m,1H,＝CH),5.03-4.95(m,1H, one proton of＝CH2),4.95-4.88(m,1H,one proton of＝CH2),3.66(s,3H,OCH3),2.30(t,J＝7.4Hz,2H,CH2),2.04(q,J＝6.9Hz,2H,CH2),1.67-1.57(m,2H,CH2),1.42-1.25(m,8H,4 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.2,139.0,114.1,51.3,34.0,33.7,29.0,28.83,28.76,24.9；IR(neat):v＝3080,2927,2855,1740,1463,1436,1361,1198,1169cm-1；MS(ESI)m/z:185(M+H)+.
实施例16
操作同本发明实施例6步骤II，1p(171.3mg,1.0mmol)，Fe(NO3)3·9H2O(24.4mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.3mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到黄色液体5p(115.9mg,56％,96％purity)(洗脱剂：石油醚/乙酸乙酯＝50/1)。
1H NMR(400MHz,CDCl3):δ＝5.87-5.73(m,2H,＝CH),5.05-4.87(m,1H,＝CH2),3.66(s,3H,OCH3),2.30(t,J＝7.4Hz,2H,CH2),2.10-1.97(m,2H,CH2),1.67-1.57(m,2H,CH2),1.42-1.20(m,10H,5 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.2,139.1,114.1,51.3,34.0,33.7,29.2,29.1,29.05,28.97,28.3,28.8,24.9；IR(neat):v＝3077,2926,2855,1740,1463,1436,1361,1197,1170cm-1；MS(ESI)m/z:199(M+H)+.
实施例17
操作同本发明实施例6步骤II，1q(126.9mg,1.0mmol)，Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5q(103.9mg,66％,98％purity)(洗脱剂：石油醚/乙酸乙酯＝30/1)。
1H NMR(400MHz,CDCl3):δ＝3.67(s,3H,OCH3),2.30(t,J＝7.6Hz,2H, CH2),2.20(td,J1＝7.0Hz,J2＝2.7Hz,2H,CH2),1.95(t,J＝2.6Hz,1H,CH),1.65(quint,J＝7.5Hz,2H,CH2),1.60-1.50(m,2H,CH2),1.48-1.38(m,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝174.0,84.2,68.3,51.4,33.8,28.1,28.0,24.3,18.1；IR(neat):v＝3295,2940,2863,1735,1460,1436,1364,1202,1172cm-1；MS(ESI)m/z:155(M+H)+.
实施例18
操作同本发明实施例1步骤I，1r(167.8mg,1.0mmol)，Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(32.1mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5r(127.6mg,65％)(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后2/1)。
1H NMR(400MHz,CDCl3):δ＝3.66(s,3H,OCH3),2.30(t,J＝7.4Hz,2H,CH2),2.17(t,J＝7.0Hz,2H,CH2),1.94(s,1H,CH),1.68-1.57(m,2H,CH2),1.52(quint,J＝7.2Hz,2H,CH2),1.45-1.24(m,8H,4 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.1,84.5,68.0,51.3,33.9,29.0,28.9,28.8,28.5,28.3,24.8,18.2；IR(neat):v＝3304,2933,2857,1737,1459,1438,1361,1197,1170cm-1；MS(ESI)m/z:197(M+H)+,219(M+Na)+.
实施例19
操作同本发明实施例1步骤I，1s(126.0mg,1.0mmol)，Fe(NO3)3·9H2O(24.9mg,0.06mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(31.7mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5s(85.3mg,55％)(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后2/1)。
1H NMR(400MHz,CDCl3):δ＝3.67(s,3H,OCH3),2.33(t,J＝7.6Hz,2H, CH2),2.20-2.06(m,2H,CH2),1.77(s,3H,CH3),1.75-1.65(m,2H,CH2),1.55-1.45(m,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.9,78.5,75.7,51.3,33.5,28.3,24.0,18.3,3.3.
实施例20
操作同本发明实施例6步骤II，1t(189.1mg,1.0mmol)，Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(16.2mg,0.1mmol)，BiCl3(31.5mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5t(90.7mg,41％,98％purity)(洗脱剂：石油醚/乙酸乙酯＝50/1)。
1H NMR(400MHz,CDCl3):δ＝7.45-7.35(m,2H,Ar-H),7.31-7.22(m,3H,Ar-H),3.67(s,3H,OCH3),2.43(t,J＝7.0Hz,2H,CH2),2.37(t,J＝7.4Hz,2H,CH2),1.87-1.75(m,2H,CH2),1.69-1.59(m,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.9,131.5,128.1,127.5,123.8,89.5,80.9,51.5,33.5,28.1,24.1,19.1；IR(neat):v＝2949,1735,1490,1437,1362,1199,1171,1145cm-1；MS(70eV,EI)m/z(％):216(M+,28.56),115(100).
实施例21
操作同本发明实施例6步骤II，1u(182.7mg,1.0mmol)，Fe(NO3)3·9H2O(31.9mg,0.08mmol)，TEMPO(12.7mg,0.08mmol)，BiCl3(31.5mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5u(108.3mg,51％)(洗脱剂：石油醚/乙酸乙酯＝15/1)。
1H NMR(400MHz,CDCl3):δ＝4.13(d,J＝2.4Hz,2H,OCH2),3.66(s,3H,OCH3),3.50(t,J＝6.4Hz,2H,OCH2),2.43(t,J＝2.4Hz,1H,CH),2.30(t,J＝7.4Hz,2H,CH2),1.70-1.52(m,4H,2 x CH2),1.42-1.26(m,6H,3 x CH2)；13C NMR (100MHz,CDCl3):δ＝174.1,79.9,74.0,70.0,57.9,51.3,33.9,29.3,28.92,28.90,25.8,24.7；IR(neat):v＝3274,2932,2857,1735,1437,1357,1249,1171,1098cm-1；MS(ESI)m/z:213(M+H)+,235(M+Na)+；HRMS calcd m/z for C12H21O3[M+H]+:213.1485,found 213.1484.
实施例22
操作同本发明实施例6步骤II，1v(233.0mg,1.0mmol)，Fe(NO3)3·9H2O(24.4mg,0.06mmol)，TEMPO(8.3mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5v(129.9mg,50％)(洗脱剂：石油醚/乙酸乙酯＝10/1至5/1)。
1H NMR(400MHz,CDCl3):δ＝7.63(d,J＝8.0Hz,2H,Ar-H),7.44(d,J＝8.0Hz,2H,Ar-H),4.55(s,2H,OCH2),3.67(s,3H,OCH3),3.51(t,J＝6.4Hz,2H,OCH2),2.33(t,J＝7.4Hz,2H,CH2),1.78-1.58(m,4H,2 x CH2),1.52-1.34(m,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.9,144.2,132.0,127.5,118.7,111.0,71.7,70.6,51.3,33.8,29.2,25.6,24.5；IR(neat):v＝2947,2863,2223,1738,1609,1448,1371,1236,1170,1099cm-1；MS(70eV,EI)m/z(％):261(M+,3.52),116(100)；HRMS calcd m/z for C15H19NO3[M]+:261.1359,Found:261.1363.
实施例23
操作同本发明实施例1步骤I，1w(290.2mg,1.0mmol)，Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5w(248.2mg,78％)(洗脱剂：石油醚/二氯甲烷＝3/1至1/1，然后1/2)。
1H NMR(400MHz,CDCl3):δ＝7.91-7.78(m,2H,Ar-H),7.77-7.65(m,2H,Ar-H),3.76-3.55(m,5H,OCH3and NCH2),2.29(t,J＝7.4Hz,2H,CH2),1.78-1.55(m,4H,2 x CH2),1.40-1.19(m,8H,4 x CH2)；13C NMR(100MHz,CDCl3):δ＝173.9,168.1,133.6,131.9,122.9,51.1,37.7,33.7,28.8,28.74,28.69,28.3,26.5,24.6；IR(neat):v＝2928,2855,1736,1707,1466,1436,1395,1170,1060cm-1；MS(70eV,EI)m/z(％):317(M+,9.61),160(100)；HRMS calcd m/z for C18H23NO4[M]+:317.1622,Found:317.1623.
实施例24
操作同本发明实施例6步骤II，1x(141.7mg,1.0mmol)，Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(8.4mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到黄色液体5x(122.0mg,73％)(洗脱剂：石油醚/乙酸乙酯＝100/1至50/1)。
1H NMR(400MHz,CDCl3):δ＝3.66(s,3H,OCH3),2.32(t,J＝7.8Hz,2H,CH2),1.77-1.59(m,5H,CH and 2x CH2),1.52(q,J＝7.5Hz,2H,CH2),1.30-1.10(m,4H,2 x CH2),0.96-0.82(m,2H,2 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.5,51.3,37.1,32.9,32.3,31.6,26.4,26.1；IR(neat):v＝2922,2851,1739,1449,1436,1366,1195,1165cm-1；MS(70eV,EI)m/z(％):170(M+,1.01),97(100).
实施例25
操作同本发明实施例1步骤I，1y(136.3mg,1.0mmol)，Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.3mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5y(105.1mg,64％)(洗 脱剂：石油醚/乙酸乙酯＝20/1)。
1H NMR(400MHz,CDCl3):δ＝7.37-7.24(m,2H,Ar-H),7.23-7.10(m,3H,Ar-H),3.67(s,3H,OCH3),2.95(t,J＝8.0Hz,2H,CH2),2.63(t,J＝7.8Hz,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.3,140.5,128.5,128.2,126.2,51.5,35.7,30.9；IR(neat):v＝3026,2950,2834,1736,1604,1496,1443,1364,1290,1255,1164,1075,1055,1028cm-1；MS(70eV,EI)m/z(％):164(M+,38.9),104(100).
实施例26
操作同本发明实施例1步骤I，1z(149.5mg,1.0mmol)，Fe(NO3)3·9H2O(24.9mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5z(115.6mg,63％,96％purity)(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后2/1)。
1H NMR(400MHz,CDCl3):δ＝7.26(t,J＝7.4Hz,2H,Ar-H),7.17(t,J＝7.4Hz,3H,Ar-H),3.64(s,3H,OCH3),2.64(t,J＝7.6Hz,2H,CH2),2.31(t,J＝7.6Hz,2H,CH2),2.31(quint,J＝7.5Hz,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.8,141.3,128.4,128.3,125.9,51.3,35.0,33.3,26.4；IR(neat):v＝3027,2946,2864,1735,1496,1442,1366,1246,1168,1146cm-1；MS(70eV,EI)m/z(％):178(M+,42.91),104(100).
实施例27
操作同本发明实施例1步骤I，1aa(167.5mg,1.0mmol)，Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(32.1mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5aa(111.8mg,59％)(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后2/1)。
1H NMR(400MHz,CDCl3):δ＝7.26(t,J＝7.4Hz,2H,Ar-H),7.20-7.12(m,3H,Ar-H),3.65(s,3H,OCH3),2.62(t,J＝6.6Hz,2H,CH2),2.32(t,J＝6.6Hz,2H,CH2),1.74-1.55(m,4H,2 x CH2)；13C NMR(100MHz,CDCl3):δ＝174.0,142.1,128.32,128.26,125.7,51.4,35.5,33.9,30.8,24.5；IR(neat):v＝3026,2943,2861,1736,1495,1436,1360,1198,1142cm-1；MS(70eV,EI)m/z(％):192(M+,3.56),91(100).
实施例28
操作同本发明实施例1步骤I，1ab(182.8mg,97％purity,1.0mmol)，Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.3mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(3mL)反应48小时得到淡黄色液体5ab(162.6mg,79％)(洗脱剂：石油醚/二氯甲烷＝15/1至5/1，然后3/1)。
1H NMR(400MHz,CDCl3):δ＝7.25(t,J＝7.2Hz,2H,Ar-H),7.20-7.09(m,3H,Ar-H),3.64(s,3H,OCH3),2.59(t,J＝7.6Hz,2H,CH2),2.28(t,J＝7.6Hz,2H,CH2),1.64(sextet,J＝7.9Hz,4H,2 x CH2),1.35(quint,J＝7.6Hz,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝174.0,142.4,128.3,128.2,125.6,51.3,35.6,33.9,30.9,28.6,24.7；IR(neat):v＝3026,2930,2857,1736,1495,1436,1362,1198,1170cm-1；MS(70eV,EI)m/z(％):206(M+,9.32),91(100).
实施例29
操作同本发明实施例6步骤II，1ac(204.1mg,1.0mmol)，Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.3mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，MeOH(162μL,4mmol)，DCE(4mL)反应48小时得到黄色液体5ac(121.8mg,51％,98％purity)(洗脱剂：石油醚/乙酸乙酯＝20/1)。
1H NMR(400MHz,CDCl3):δ＝7.51-7.44(m,2H,Ar-H),7.42-7.34(m,2H, Ar-H),3.67(s,3H,OCH3),3.01(t,J＝7.8Hz,2H,CH2),2.66(t,J＝7.6Hz,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝172.8,141.4,131.7,130.8(q,J＝31.9Hz),128.9,125.0(q,J＝3.7Hz),124.1(q,J＝270.4Hz),123.2(q,J＝3.7Hz),51.6,35.3,30.6；19F NMR(376MHz,CDCl3):δ＝-63.1；IR(neat):v＝1737,1439,1365,1327,1199,1159,1118,1073cm-1；MS(70eV,EI)m/z(％):232(M+,44.2),172(100).
实施例30
操作同本发明实施例6步骤II，1ad(161.1mg,1.0mmol)，Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.3mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(4mL)反应60小时得到黄色液体5ad(89.7mg,47％)(洗脱剂：石油醚/乙酸乙酯＝10/1至8/1)。
1H NMR(400MHz,CDCl3):δ＝7.58(d,J＝8.4Hz,2H,Ar-H),7.32(d,J＝8.4Hz,2H,Ar-H),3.67(s,3H,OCH3),3.02(t,J＝7.6Hz,2H,CH2),2.66(t,J＝7.6Hz,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝172.5,146.0,132.2,129.1,118.8,110.1，51.6,34.7,30.7；IR(neat):v＝2952,2227,1733,1608,1506,1437,1365,1174,1159cm-1；MS(70eV,EI)m/z(％):189(M+,21.63),129(100).
实施例31
操作同本发明实施例6步骤II，1ae(181.1mg,1.0mmol)，Fe(NO3)3·9H2O(33.0mg,0.08mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(31.7mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(4mL)反应48小时得到黄色液体5ae(89.0mg,43％)(洗 脱剂：石油醚/乙酸乙酯＝8/1至5/1)。
1H NMR(400MHz,CDCl3):δ＝8.15(d,J＝8.4Hz,2H,Ar-H),7.38(d,J＝8.4Hz,2H,Ar-H),3.68(s,3H,OCH3),3.07(t,J＝7.4Hz,2H,CH2),2.69(t,J＝7.4Hz,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝172.5,148.2,146.6,129.1,123.7,51.7,34.7,30.5；IR(neat):v＝3113,3083,1727,1607,1514,1430,1346,1191,1169cm-1；MS(70eV,EI)m/z(％):209(M+,26.18),149(100).
实施例32
操作同本发明实施例6步骤II，1af(169.9mg,1.0mmol)，Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(4mL)反应48小时得到黄色液体5af(103.2mg,52％)(洗脱剂：石油醚/乙酸乙酯＝25/1至20/1)。
1H NMR(400MHz,CDCl3):δ＝7.30-7.20(m,2H,Ar-H),7.17-7.07(m,2H,Ar-H),3.66(s,3H,OCH3),2.91(t,J＝7.6Hz,2H,CH2),2.60(t,J＝7.8Hz,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.0,138.9,132.0,129.6,128.5,51.6,35.4,30.2；IR(neat):v＝2951,1734,1492,1436,1364,1195,1157,1092cm-1；MS(70eV,EI)m/z(％):200(M(37Cl)+,9.7),198(M(35Cl)+,29.17),138(100).
实施例33
操作同本发明实施例6步骤II，1ag(175.5mg,95％purity,1.0mmol)，Fe(NO3)3·9H2O(32.3mg,0.08mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(32.0mg,0.1mmol)，MeOH(202μL,5mmol)，DCE(4mL)反应48小时得到黄色液体5ag(107.3mg,55％)(洗脱剂：石油醚/乙酸乙酯＝15/1至10/1)。
1H NMR(400MHz,CDCl3):δ＝7.10(d,J＝8.8Hz,2H,Ar-H),6.82(d,J＝ 8.4Hz,2H,Ar-H),3.76(s,3H,OCH3),3.65(s,3H,OCH3),2.88(t,J＝7.8Hz,2H,CH2),2.59(t,J＝7.8Hz,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝173.3,158.0,132.5,129.1,113.8,55.1,51.4,35.9,30.0；IR(neat):v＝3011,2929,1729,1610,1511,1436,1373,1176,1157cm-1；MS(70eV,EI)m/z(％):194(M+,21.47),121(100).
实施例34
操作同本发明实施例1步骤I，1a(2.4195g,10.0mmol)，Fe(NO3)3·9H2O(244.8mg,0.6mmol),TEMPO(79.1mg,0.5mmol),BiCl3(313.3mg,1.0mmol),MgSO4(702.4mg)，MeOH(1.2mL,30mmol)，DCE(30mL)反应48小时得到白色固体5a(2.1826mg,81％)(洗脱剂：石油醚/乙酸乙酯＝200/1至80/1)。
1H NMR(400MHz,CDCl3):δ＝3.66(s,3H,OCH3),2.30(t,J＝7.4Hz,2H,CH2),1.62(quint,J＝7.2Hz,2H,CH2),1.37-1.18(m,24H,12 x CH2),0.88(t,J＝6.8Hz,3H,CH3)；13C NMR(100MHz,CDCl3):δ＝174.1,51.2,34.0,31.9,29.62,29.61,29.59,29.5,29.4,29.3,29.2,29.1,24.9,22.6,14.0.
实施例35
操作同本发明实施例1步骤I，1a(10.8905g,45.0mmol)，Fe(NO3)3·9H2O(552.0mg,1.35mmol),TEMPO(215.6mg,1.35mmol),AlCl3(605.8mg,4.5mmol),MgSO4(2.9995g)，MeOH(5.3mL,135mmol)，DCE(90mL)反应48小时得到白色固体5a(9.0110g,74％)(洗脱剂：石油醚/二氯甲烷＝5/1至4/1，然后3/1，然后石油醚/乙酸乙酯＝40/1)。
1H NMR(400MHz,CDCl3):δ＝3.66(s,3H,OCH3),2.30(t,J＝7.4Hz,2H,CH2),1.62(quint,J＝7.2Hz,2H,CH2),1.37-1.18(m,24H,12 x CH2),0.88(t,J＝ 6.8Hz,3H,CH3)；13C NMR(100MHz,CDCl3):δ＝174.1,51.2,34.0,31.9,29.62,29.61,29.59,29.5,29.4,29.3,29.2,29.1,24.9,22.6,14.0.
实施例36
向1L的圆底瓶中依次加入Fe(NO3)3·9H2O(1.2246g,3mmol)，TEMPO(478.3mg,3mmol)，AlCl3(1.3472g,10mmol)，1c(22.8mL,d＝0.833g/mL,100mmol)，MeOH(12.2mL,300mmol)和DCE(200mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(200mL)，旋蒸旋去溶剂，得到5c，粗谱显示核磁收率为73％
实施例37
操作同本发明实施例6步骤II，1q(631.8mg,5.0mmol)，Fe(NO3)3·9H2O(121.6mg,0.3mmol)，TEMPO(40.0mg,0.25mmol)，BiCl3(157.1mg,1.5mmol)，MgSO4(249.6mg)，MeOH(0.6mL,15mmol)，DCE(15mL)反应48小时得到淡黄色液体5q(516.2mg,65％,97％purity)(洗脱剂：石油醚/乙酸乙酯＝49/1至24/1)。
1H NMR(400MHz,CDCl3):δ＝3.67(s,3H,OCH3),2.30(t,J＝7.4Hz,2H,CH2),2.25-2.13(m,2H,CH2),1.99-1.91(m,1H,CH),1.65(quint,J＝7.3Hz,2H,CH2),1.55(quint,J＝7.0Hz,2H,CH2),1.50-1.38(m,2H,CH2)；13C NMR(100MHz,CDCl3):δ＝174.0,84.2,68.3,51.4,33.8,28.1,28.0,24.3,18.1.
实施例38
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，1aj(154.9mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5aj，粗谱显示核磁收率为18％，相应的醛3aj核磁收率为57％，缩甲醛7aj核磁收率为33％。
实施例39
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，1ak(140.9mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5ak，粗谱显示核磁收率为16％，相应的醛3ak核磁收率为83％。
实施例40
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(31.2mg,0.1mmol)，1al(135.9mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5al，粗谱显示核磁收率为11％，相应的醛3al核磁收率为77％。
实施例41
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(33.1mg,0.08mmol)，TEMPO(8.4mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，1am(204.6mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5am，粗谱显示核磁收率为43％，相应的醛3am核磁收率为15％，缩甲醛7am核磁收率为17％。
实施例42
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，1an(126.2mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5an，粗谱显示核磁收率为34％，相应的醛3an核磁收率为26％，缩甲醛7an核磁收率为30％。
实施例43
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.4mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(32.6mg,0.1mmol)，1ao(138.5mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5ao，粗谱显示核磁收率为30％，相应的醛3ao核磁收率为46％，缩甲醛7ao核磁收率为10％。
实施例44
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.4mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，1ap(188.3mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5ap，粗谱显示核磁收率为36％，相应的醛3ap核磁收率为14％，缩甲醛7ap核磁收率为32％。
实施例45
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(25.1mg,0.06mmol)，TEMPO(8.3mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，1aq(135.9mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5aq，粗谱显示核磁收率为22％，相应的醛3aq核磁收率为64％。
实施例46
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.4mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，1ar(128.2mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5ar，粗谱显示核磁收率为25％，相应的醛3ar核磁收率为5％，缩甲醛7ar核磁收率为14％。
实施例47
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.9mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，AlCl3(13.2mg,0.1mmol)，1a(242.1mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为74％，相应的醛3a核磁收率为16％，缩甲醛7a核磁收率为8％。
实施例48
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(7.9mg,0.05mmol)，FeCl3(16.0mg,0.1mmol)，1a(242.3mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为31％，相应的醛3a核磁收率为33％，缩甲醛7a核磁收率为22％。
实施例49
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(25.0mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，InCl3(21.9mg,0.1mmol)，1a(242.9mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为35％，相应的醛3a核磁收率为29％，缩甲醛7a核磁收率为7％。
实施例50
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(25.1mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，InBr3(35.2mg,0.1mmol)，1a(241.8mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。 反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为57％，相应的醛3a核磁收率为10％，缩甲醛7a核磁收率为11％。
实施例51
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，4-NHAc-TEMPO(10.8mg,0.05mmol)，BiCl3(32.3mg,0.1mmol)，1a(242.8mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为21％，相应的醛3a核磁收率为42％，缩甲醛7a核磁收率为18％。
实施例52
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.6mg,0.06mmol)，4-OMe-TEMPO(9.6mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，1a(242.7mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为81％，相应的醛3a核磁收率为11％，缩甲醛7a核磁收率为3％。
实施例53
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.8mg,0.06mmol)，4-OH-TEMPO(8.7mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，1a(242.0mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶 剂，得到5a，粗谱显示核磁收率为40％，相应的醛3a核磁收率为33％，缩甲醛7a核磁收率为18％。
实施例54
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(31.3mg,0.1mmol)，1a(242.9mg,1.0mmol)，MeOH(202μL,5mmol)和CHCl3(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为25％，相应的醛3a核磁收率为43％，缩甲醛7a核磁收率为31％。
实施例55
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(31.5mg,0.1mmol)，1a(242.4mg,1.0mmol)，MeOH(202μL,5mmol)和甲苯(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为44％，相应的醛3a核磁收率为30％，缩甲醛7a核磁收率为15％。
实施例56
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.7mg,0.1mmol)，1a(242.0mg,1.0mmol)，MeOH(202μL,5mmol)和1,4-二氧六环(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为21％，相应的醛3a核磁收率为20％，缩甲醛7a核磁收率为1％。
实施例57
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.4mg,0.06mmol)，TEMPO(8.1mg,0.05mmol)，BiCl3(31.9mg,0.1mmol)，1a(242.7mg,1.0mmol)，MeOH(122μL,3mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为65％，相应的醛3a核磁收率为26％，缩甲醛7a核磁收率为3％。
实施例58
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(31.8mg,0.1mmol)，1a(242.7mg,1.0mmol)，MeOH(162μL,4mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为71％，相应的醛3a核磁收率为22％，缩甲醛7a核磁收率为5％。
实施例59
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(32.6mg,0.1mmol)，1a(242.1mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为74％，相应的醛3a核磁收率为14％，缩甲醛7a核磁收率为8％。
实施例60
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，1a(242.5mg,1.0mmol)，MeOH(244μL,6mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为75％，相应的醛3a核磁收率为15％，缩甲醛7a核磁收率为7％。
实施例61
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，1a(242.5mg,1.0mmol)，MeOH(284μL,7mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为74％，相应的醛3a核磁收率为15％，缩甲醛7a核磁收率为10％。
实施例62
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.8mg,0.06mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(31.5mg,0.1mmol)，1a(242.4mg,1.0mmol)，MeOH(324μL,8mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为67％，相应的醛3a核磁收率为16％，缩甲醛7a核磁收率为14％。
实施例63
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(32.2mg,0.08mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(34.7mg,0.11mmol)，1a(242.6mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。 反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为73％，相应的醛3a核磁收率为19％，缩甲醛7a核磁收率为6％。
实施例64
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(28.4mg,0.07mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(31.9mg,0.10mmol)，1a(241.6mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为76％，相应的醛3a核磁收率为13％，缩甲醛7a核磁收率为9％。
实施例65
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(32.7mg,0.08mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(32.0mg,0.1mmol)，1a(242.6mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为77％，相应的醛3a核磁收率为14％，缩甲醛7a核磁收率为4％。
实施例66
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(19.0mg,0.06mmol)，1a(243.0mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(4mL)。插上氧气球，反应在50℃油浴下搅拌40小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为64％，相应的醛3a核磁收率为22％，缩甲醛7a核磁收率为8％。
实施例67
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.9mg,0.06mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(31.6mg,0.1mmol)，1a(241.1mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在25℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为52％，相应的醛3a核磁收率为8％，缩甲醛7a核磁收率为25％。
实施例68
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(31.4mg,0.1mmol)，1a(241.3mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在35℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为76％，相应的醛3a核磁收率为7％，缩甲醛7a核磁收率为9％。
实施例69
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.5mg,0.06mmol)，TEMPO(7.9mg,0.05mmol)，BiCl3(31.9mg,0.1mmol)，1a(242.7mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在40℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为80％，相应的醛3a核磁收率为10％，缩甲醛7a核磁收率为5％。
实施例70
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.7mg,0.06mmol)，TEMPO (7.9mg,0.05mmol)，BiCl3(32.5mg,0.1mmol)，1a(242.5mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在45℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为81％，相应的醛3a核磁收率为11％，缩甲醛7a核磁收率为7％。
实施例71
向25mL的茄形瓶中依次加入Fe(NO3)3·9H2O(24.2mg,0.06mmol)，TEMPO(8.2mg,0.05mmol)，BiCl3(31.0mg,0.1mmol)，1a(241.9mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在60℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为56％，相应的醛3a核磁收率为31％，缩甲醛7a核磁收率为5％。
实施例72
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(8.0mg,0.05mmol)，BiCl3(31.5mg,0.1mmol)，1a(243.5mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上空气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a，粗谱显示核磁收率为33％，相应的醛3a核磁收率为39％，缩甲醛7a核磁收率为22％。
实施例73
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.6mg,0.06mmol)，TEMPO(8.3mg,0.05mmol)，BiCl3(32.3mg,0.1mmol)，1a(242.0mg,1.0mmol)，EtOH(231.6mg,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，得到5a-A， 粗谱显示核磁收率为14％，相应的醛3a核磁收率为58％。
对比例1
向50mL的圆底瓶中依次加入Fe(NO3)3·9H2O(24.2mg,0.06mmol)，TEMPO(8.3mg,0.05mmol)，KCl(7.8mg,0.1mmol)，1a(242.4mg,1.0mmol)，MeOH(202μL,5mmol)和DCE(3mL)。插上氧气球，反应在50℃油浴下搅拌48小时。反应液过硅胶短柱(3cm)，乙醚洗脱(3 x 25mL)，旋蒸旋去溶剂，粗产品中加入2mL甲醇，1mL饱和亚硫酸氢钠溶液，剧烈搅拌1h，加无水硫酸钠干燥，过硅胶短柱(1cm)，DCM洗脱(3 x 15mL)，旋蒸旋去溶剂，利用硅胶柱层析法进行分离纯化(洗脱剂：石油醚/二氯甲烷＝10/1至4/1，然后2/1)，无法得到产物5a。
实施例74
本发明探讨醇类对反应产物的影响，结果发现甲醇效果最佳，乙醇和正丙醇能有相应酯化产物，但效率很低，其他醇反应不能得到目标产物5，详见表1。
表1
本发明的保护内容不局限于以上实施例。在不背离本发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。

Claims (11)

  1. 一种铁催化的醇直接氧化酯化制备羧酸酯类化合物的方法，其特征在于，所述方法在25℃-60℃的条件下，在有机溶剂中，以醇为原料，以九水合硝酸铁、氮氧化物和Lewis酸为催化剂，以氧气或空气作为氧化剂，将所述醇直接氧化酯化生成羧酸酯类化合物；所述醇为R1CH2OH和R2OH；
    所述反应过程如反应式(1)所示：
    其中，
    所述R1包括烷基，带有官能团的烷基，带有官能团的苯基；
    所述带有官能团的烷基中的官能团为卤素、醚键、酯基、环烷基、芳基、杂芳基、烯基、炔基、联烯基、带官能团的炔基、氨基；
    所述带有官能团的炔基中的官能团为烷基、苯基；
    所述带有官能团的苯基为烷氧基、硝基；
    所述R2OH为甲醇或乙醇。
  2. 如权利要求1所述的方法，其特征在于，所述R1包括C1-C20的烷基，带有官能团的C1-C20的烷基；
    所述带有官能团的烷基中的官能团为氟、氯、溴、碘、醚键、酯基、烯基、炔基、联烯基、苯基、对氯苯基、烷基苯基、间甲氧基苯基、烷氧基萘基、联苯基、对硝基苯基、对氰基苯基、酯基取代的苯基、噻吩基、氨基。
  3. 如权利要求1所述的方法，其特征在于，所述氮氧化物为2,2,6,6-四甲基哌啶氮氧化物(TEMPO)、4-乙酰氨基-2,2,6,6-四甲基哌啶氮氧化物(4-NHAc-TEMPO)、4-甲氧基-2,2,6,6-四甲基哌啶氮氧化物(4-OMe-TEMPO)、4-羟基-2,2,6,6-四甲基哌啶氮氧化物(4-OH-TEMPO)、9-氮杂双环[3.3.1]壬烷-N-氧基自由基(ABNO)之一种或几种。
  4. 如权利要求1所述的方法，其特征在于，所述Lewis酸为氯化铋、氯化铝、氯化铁、氯化铟、溴化铟、溴化铋、氯化锡、氟化铜、氯化锌、三氟甲磺酸镱、三氟甲磺酸镧、三氟甲磺酸钪之一种或几种。
  5. 如权利要求1所述的方法，其特征在于，所述有机溶剂为二氯甲烷、1,2- 二氯乙烷、1,1-二氯乙烷、三氯甲烷、甲苯、乙腈、氯仿、乙酸乙酯、1,3-二氯丙烷、1,2-二氯丙烷、硝基甲烷、乙二醇二甲醚、二氧六环中的一种或多种混合。
  6. 如权利要求1所述的方法，其特征在于，所述的原料醇R1CH2OH与R2OH的摩尔比例为1：(1-8)。
  7. 如权利要求1所述的方法，其特征在于，所述的原料醇R1CH2OH、九水合硝酸铁、氮氧化物、Lewis酸的摩尔比例为100：(1-10)：(1-10)：(1-11)。
  8. 如权利要求1所述的方法，其特征在于，所述反应的时间为40-60小时。
  9. 如权利要求1所述的方法，其特征在于，所述反应氧气的来源为纯的氧气或空气。
  10. 如权利要求1所述的方法，其特征在于，所述反应的温度为25℃-60℃。
  11. 按如权利要求1-10之任一项所述方法制备得到的羧酸酯类化合物。
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