A method for preparing carboxylic acid esters by iron-catalyzed oxidation esterification of alcohols

Abstract

A method for the preparation of carboxylic acid esters by iron-catalyzed oxidation esterification of alcohols. The present invention discloses a method for directly oxidizing and esterifying alcohols to prepare carboxylic acid ester compounds with oxygen or air as the oxidant under iron catalysis. The method is carried out at 25 °C - 60 °C in an organic solvent, using iron nitrate (Fe(NO3)3·9H2O), nitrogen oxides and Lewis acid as catalysts, and oxygen or air as the oxidant, and the alcohol is directly oxidized and esterified to form carboxylic acid ester compounds. The present invention has many advantages such as simple operation, cheap and easily available catalysts and raw materials, mild reaction conditions, excellent yield, good compatibility of substrate functional groups, scalable reaction scale, environmentally friendly reaction process and no pollution, and has the prospect of industrial application.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical synthesis, and relates to a method for directly oxidizing and esterifying an alcohol to prepare a carboxylic acid ester compound by using iron catalysis and oxygen or air as an oxidant. Background Art

[0002] Carboxylic esters are widely present in bulk chemicals, fine chemicals, natural products, and polymers (Otera, J. Esterification: Methods, Reactions, and Applications, Wiley-VCH, Weinheim, 2003.). Due to their wide range of uses, the synthesis of ester compounds has also attracted much attention. Traditional methods generally involve nucleophilic substitution reactions of carboxylic acid derivatives (acyl halides, acid anhydrides, etc.) with alcohols, but these reactions often require relatively harsh reaction conditions and produce stoichiometric amounts of by-products (Otera, J. Chem. Rev. 1993, 93, 1449.). In recent years, there have also been numerous reports on the oxidative esterification reaction of aldehydes with alcohols, but currently this route still requires stoichiometric amounts of oxidants, such as 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.), etc., which will cause a certain burden on the environment, and the aldehydes required for the reaction are often obtained by selective oxidation of alcohols.From the perspective of green and sustainable development, oxygen is an inexpensive, readily available, abundant, and environmentally friendly oxidant. Therefore, the use of oxygen as an oxidant has currently attracted extensive interest (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.). Therefore, the direct oxidative esterification of alcohols using oxygen as an oxidant is considered an ideal method for synthesizing ester compounds. However, to achieve the above reaction, it currently depends on the use of noble metals, etc. (Shi, Z.; Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3381.). Iron, as the most abundant metal in the earth's crust, is widely used in catalyzing various reactions and shows excellent performance especially in oxidation reactions. TEMPO, as a type of stable nitroxide radical, exhibits unique reactivity in the co-catalytic oxidation of alcohols with Fe or Cu. However, in the Fe / TEMPO system, the oxidative esterification of alcohols using oxygen or air as an oxidant has not been reported yet. Summary of the Invention

[0003] The present invention overcomes the deficiencies of the prior art and provides a method for preparing carboxylic ester compounds by the iron-catalyzed oxidative esterification of alcohols using oxygen or air as an oxidant, which has low cost, is suitable for industrial production, has mild reaction conditions, is easy to operate, and is green. In the prior art, there has been no report on the oxidative esterification of alcohols using oxygen or air as an oxidant in the Fe / TEMPO system.

[0004] The present invention overcomes the defects in the existing oxidation technologies, such as using equivalent or excessive oxidants or precious metals as catalysts, with severe reaction conditions, unavailable raw materials, and high costs. It provides a method for the oxidative esterification of alcohols by using greener, cleaner, and cheaper oxygen or air as an oxidant under atmospheric pressure conditions. The reaction uses ferric nitrate nonahydrate, nitrogen oxides, and Lewis acids, which are industrially available and inexpensive, as catalysts, and oxygen or air as an oxidant, successfully achieving the oxidative esterification of alcohols. The present invention has the beneficial effects of low cost, wide raw material sources, a green and clean reaction process, low cost, suitability for industrial production, mild reaction conditions, simple operation, and environmental friendliness.

[0005] The present invention provides a method for directly oxidatively esterifying alcohols to prepare carboxylic ester compounds using iron catalysis with oxygen or air as an oxidant. Under the conditions of 25°C - 60°C, in an organic solvent, using two alcohols as raw materials, ferric nitrate nonahydrate, nitrogen oxides, and Lewis acids as catalysts, and oxygen or air as an oxidant, the alcohols are directly oxidatively esterified to form carboxylic ester compounds. In a specific embodiment, the two alcohols are R 1 CH2OH and R 2 OH. The reaction process is shown in Reaction Scheme (1):

[0006]

[0007] Among them,

[0008] the R 1 includes alkyl groups, alkyl groups with functional groups, and phenyl groups with functional groups;

[0009] The functional groups in the alkyl groups with functional groups are halogen, ether bond, ester group, cycloalkyl group, aryl group, heteroaryl group, alkenyl group, alkynyl group, allene group, alkynyl group with functional groups, amino group, etc.; the aryl groups are phenyl group, halogenated phenyl group, alkylphenyl group, alkoxyphenyl group, alkoxynaphthyl group, biphenyl group, nitrophenyl group, phenyl group substituted with an ester group, cyanophenyl group, m-trifluoromethylphenyl group, etc.; the heteroaryl groups are thiophenyl group, etc.;

[0010] The functional groups in the alkynyl groups with functional groups are alkyl group, phenyl group, etc.;

[0011] The functional groups in the phenyl groups with functional groups are alkoxy group, nitro group, etc.;

[0012] the R 2 OH is methanol or ethanol.

[0013] Preferably, the R 1 includes C1 - C20 alkyl groups, C1 - C20 alkyl groups with functional groups;

[0014] The functional groups in the alkyl group with functional groups are fluorine, chlorine, bromine, iodine, ether bond, ester group, alkenyl group, alkynyl group, alleny group, phenyl group, p-chlorophenyl group, alkylphenyl group, m-methoxyphenyl group, alkoxynaphthyl group, biphenyl group, p-nitrophenyl group, p-cyanophenyl group, phenyl group substituted by ester group, thiophenyl group, amino group.

[0015] Further preferably, R 1 includes C3-C20 alkyl groups and C3-C20 alkyl groups with functional groups;

[0016] Specifically, the R 1 CH2OH is octadecanol, hexadecanol, dodecanol, 9-bromo-1-nonanol, 9-iodo-1-nonanol, 9-phenoxy-1-nonanol, 6-ethoxy-1-hexanol, 8-(toluene-4-sulfonyloxy)-octanol, 6-(methylsulfonyl)-hexanol, acetic acid-(8-hydroxyoctyl) ester, benzoic acid-(6-hydroxyhexyl) ester, methyl 6-hydroxyhexanoate, ethyl 6-hydroxyhexanoate, benzyl 6-hydroxyhexanoate, 10-undecen-1-ol, 9-decen-1-ol, 10-undecyn-1-ol, 7-octyn-1-ol, 6-octyn-1-ol, 7-phenyl-6-octyn-1-ol, 8-(propyl-2-yn-1-yloxy)-octanol, 4-(((6-hydroxyethyl)oxy)methyl)benzonitrile, 2-(9-hydroxynonyl)isoindoline-1,3-dione, 3-cyclohexyl-1-propanol, phenylhexanol, phenylpentanol, phenylbutanol, phenylpropanol, p-cyanophenylpropanol, p-nitrophenylpropanol, 3-trifluoromethylphenylpropanol, p-chlorophenylpropanol, p-methoxyphenylpropanol, p-nitrobenzyl alcohol, p-methoxybenzyl alcohol, 3-bromo-phenethyl alcohol, 2-phenylpropanol, thiophene-2-ethanol, adamantanemethanol, cinnamyl alcohol, 4-hydroxyethylbiphenyl, 6,7-diene-1-octanol.

[0017] In the method of the present invention, the nitrogen oxides are one or more of 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO), 4-acetamido-2,2,6,6-tetramethylpiperidine N-oxide (4-NHAc-TEMPO), 4-methoxy-2,2,6,6-tetramethylpiperidine N-oxide (4-OMe-TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxide (4-OH-TEMPO), 9-azabicyclo[3.3.1]nonane-N-oxy radical (ABNO), etc.; preferably, the nitrogen oxides are 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO), 4-methoxy-2,2,6,6-tetramethylpiperidine N-oxide (4-OMe-TEMPO); further preferably, it is 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO).

[0018] In the method of the present invention, the Lewis acid is one or more of bismuth chloride, aluminum chloride, iron chloride, indium chloride, indium bromide, bismuth bromide, tin chloride, copper fluoride, zinc chloride, ytterbium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, scandium trifluoromethanesulfonate, etc.; preferably, the Lewis acid is bismuth chloride, aluminum chloride; more preferably, it is bismuth chloride.

[0019] In the method of the present invention, the organic solvent is one or a mixture of more of dichloromethane, 1,2-dichloroethane, 1,1-dichloroethane, chloroform, toluene, acetonitrile, chloroform, ethyl acetate, 1,3-dichloropropane, 1,2-dichloropropane, nitromethane, ethylene glycol dimethyl ether, dioxane, etc.; preferably, the organic solvent is 1,2-dichloroethane, toluene; more preferably, it is 1,2-dichloroethane.

[0020] In the method of the present invention, the starting alcohol R 1 CH2OH and R 2 The molar ratio of OH is 1:(1 - 8); preferably, the molar ratio of the starting alcohol R 1 CH2OH and R 2 The molar ratio of OH is 1:(4 - 5); more preferably, it is 1:5.

[0021] In the method of the present invention, the starting alcohol R 1 The molar ratio of CH2OH, ferric nitrate nonahydrate, nitrogen oxides, and Lewis acid is 100:(1 - 10):(1 - 10):(1 - 11); preferably, the molar ratio of the starting alcohol R 1 CH2OH, ferric nitrate nonahydrate, nitrogen oxides, and Lewis acid is 100:(6 - 8):5:10; more preferably, it is 100:6:5:10.

[0022] In the present invention, the reaction temperature is 25 - 60 °C; preferably, the reaction temperature is 40 - 50 °C; more preferably, the reaction temperature is 50 °C.

[0023] In the present invention, the reaction time is 40 - 60 hours, preferably, it is 48 hours.

[0024] In the present invention, the source of oxygen is pure oxygen or air.

[0025] The possible mechanism of the present invention is as follows: First, the alcohol is oxidized to obtain an aldehyde under the combined action of ferric nitrate, TEMPO, and a Lewis acid (such as BiCl3); then, the aldehyde is attacked by methanol to form a hemiacetal or acetal, and the acetal can return to the hemiacetal under the action of BiCl3, and finally the hemiacetal is oxidized to obtain the corresponding methyl ester product, and the reaction mechanism is shown in the following formula (2).

[0026] The present invention verified through monitoring reactions that aldehydes are intermediates of the reactions described in the present invention, and almost no acids were detected during the reaction process. The monitoring reaction diagram is as shown in Figure 1 which further proves that the formation of acids is not involved in the reaction system of the present invention. In addition, in the reaction system of the present invention, BiCl3 or AlCl3, etc. play the role of Lewis acids rather than ordinary inorganic chlorides.

[0027]

[0028] The essential innovative points of the present invention are as follows: (1) Starting from the catalytic system, the present invention utilizes a new catalytic system of iron nitrate, nitrogen oxides, and Lewis acid, enabling the direct oxidative esterification of two alcohols to obtain carboxylic acid esters, which cannot obtain the corresponding carboxylic acid esters under the previously reported catalytic system of iron nitrate, nitrogen oxides, and inorganic halides. See Comparative Example 1 of the present invention for details. (2) Starting from the concept of oxidative esterification of alcohols, the present invention proposes a convenient and simple method to achieve the oxidative esterification of two alcohols. Most of the previously reported methods rely on the trial of precious metals such as Au and Pd, which greatly increases the production cost. The iron / TEMPO system is not only cheaper but also has not been reported before.

[0029] 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 CH2OH and R 2 OH as raw materials, with ferric nitrate nonahydrate, nitrogen oxides, and Lewis acid as catalysts, and using oxygen or air as an oxidant, the alcohols are directly oxidatively esterified to form carboxylic acid esters. The present invention uses oxygen or air as an oxidant, and can oxidatively esterify primary alcohols containing various functional groups (such as halogen, ether bond, ester group, alkenyl, alkynyl, etc.) to obtain carboxylic acid esters. The present invention has a wide substrate generality and a high yield, and uses cheap and green iron nitrate, TEMPO, and bismuth chloride as catalysts, and oxygen or air, which is rich in reserves and easily available, as an oxidant, effectively solving the problems of narrow substrate generality, the need for precious metals to participate, and the use of equivalent or excessive toxic oxidants in the current methods. The present invention has many advantages such as simple operation, cheap and easily available catalysts and raw materials, mild reaction conditions, excellent yield, good compatibility of substrate functional groups, the reaction scale can be enlarged, and the reaction process is environmentally friendly and pollution-free. The method of the present invention can be used for both small-scale laboratory synthesis and large-scale industrial production.

[0030] The present invention uses oxygen or air, which is a green, inexpensive, and widely available clean energy source, to replace the chemical oxidants required in traditional oxidation methods as oxidants. Its by-product is water, and almost no pollution to the environment is generated during the whole reaction process, meeting the requirements of green chemistry. Ferric nitrate nonahydrate, nitrogen oxides, and Lewis acids used in the method of the present invention are all commercially available reagents, and they are inexpensive and have a high yield, which can effectively reduce production costs. The reaction conditions of the present invention are mild and the post-treatment is simple, so the operation is convenient and easy to control. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is a monitoring reaction diagram of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0032] Combined with the following specific embodiments, the present invention will be further described in detail. The processes, conditions, experimental methods, etc. for implementing the present invention, except for the specifically mentioned content below, are all common knowledge and well-known general knowledge in the art, and the present invention has no particularly restricted content.

[0033] Note: In the reaction formulas of the following examples, mol represents mole; Fe(NO3)3·9H2O represents ferric nitrate nonahydrate(III); TEMPO represents 2,2,6,6-tetramethylpiperidine oxide; BiCl3 represents bismuth chloride; DCE represents 1,2-dichloroethane; Et2O represents diethyl ether; DCM represents dichloromethane; CHCl3 represents chloroform; toluene represents toluene; dioxane represents 1,4-dioxane; O2 balloon means the reaction is carried out in an oxygen atmosphere provided by an oxygen balloon; Air balloon means the reaction is carried out in an air atmosphere provided by an air balloon; h represents hour; the boiling range of petroleum ether is 60 - 90 °C; the NMR yield is determined by 1 1H NMR, with dibromomethane as the internal standard and the silica gel mesh number being 300 - 400.

[0034] Example 1

[0035]

[0036] Step I: Add Fe(NO3)3·9H2O (24.3 mg, 0.06 mmol), TEMPO (8.4 mg, 0.05 mmol), BiCl3 (31.3 mg, 0.1 mmol), 1a (241.4 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) into a 50 mL round-bottom flask in sequence. Insert an oxygen balloon, and the reaction is stirred in an oil bath at 50 °C for 48 h. The reaction solution is passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), the solvent is removed by rotary evaporation. 2 mL of methanol and 1 mL of saturated sodium bisulfite solution are added to the crude product, and it is vigorously stirred for 1 h, dried with anhydrous sodium sulfate, passed through a silica gel column (1 cm), eluted with DCM (3 x 15 mL), the solvent is removed by rotary evaporation, and separation and purification are carried out by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 2 / 1) to obtain the product 5a as a pale yellow solid (188.0 mg, 70%).

[0037] 1 1H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H, OCH3), 2.30 (t, J = 7.4 Hz, 2H, CH2), 1.67 - 1.56 (m, 2H, CH2), 1.34 - 1.17 (m, 24H, 12xCH2), 0.88 (t, J = 6.6 Hz, 3H, CH3); 13 13C NMR (100 MHz, 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, 1164 cm -1 ; MS (70 eV, EI) m / z (%): 270 (M + , 19.23), 74 (100).

[0038] Example 2

[0039]

[0040] The operation was the same as that in Step I of Example 1 of the present invention. 1b (270.5 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a white solid 5b (217.8 mg, 73%) (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 2 / 1).

[0041] m.p. 42.1 - 43.5 °C (low melting solid, unable to recrystallize, directly measured melting point); 1 1H NMR (400 MHz, CDCl3) δ = 3.66 (s, 3H, OCH3), 2.30 (d, J = 7.6 Hz, 2H, CH2), 1.65 - 1.58 (m, 2H, CH2), 1.32 - 1.17 (m, 28H, 14xCH2), 0.88 (t, J = 6.4 Hz, 3H, CH3); 13 13C NMR (100 MHz, 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, 1105 cm -1 ; MS (70 eV, EI) m / z (%): 298 (M + , 43.97), 74 (100).

[0042] Example 3

[0043]

[0044] The operation was the same as that in Step I of Example 1 of the present invention. 1c (186.4 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5c (160.7 mg, 75%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0045] 11H NMR (400 MHz, CDCl3) δ = 3.67 (s, 3H, OCH3), 2.30 (t, J = 7.6 Hz, 2H, CH2), 1.70 - 1.57 (m, 2H, CH2), 1.45 - 1.15 (m, 16H, CH2×8), 0.88 (t, J = 6.6 Hz, 3H, CH3); 13 13C NMR (100 MHz, 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, 1116 cm -1 ; MS (70 eV, EI) m / z (%): 214 (M + , 4.71), 74 (100).

[0046] Example 4

[0047]

[0048] The operation was the same as in Step I of Example 1 of the present invention. 1d (223.5 mg, 1.0 mmol), Fe(NO3)3·9H2O (32.3 mg, 0.08 mmol), TEMPO (8.3 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5d (189.5 mg, 74%, 98% purity) (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 2 / 1).

[0049] 1 1H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H, OCH3), 3.40 (t, J = 6.8 Hz, 2H, CH2), 2.30 (t, J = 7.4 Hz, 2H, CH2), 1.85 (quint, J = 7.1 Hz, 2H, CH2), 1.68 - 1.56 (m, 2H, CH2), 1.48 - 1.37 (m, 2H, CH2), 1.32 (s, 6H, 3xCH2); 13 13C NMR (100 MHz, 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, 1170 cm-1 ; MS(ESI) m / z: 275 (M( 81 Br)+Na) + , 273 (M( 79 Br)+Na) + .

[0050] Example 5

[0051]

[0052] The operation was the same as in Step I of Example 1 of the present invention. 1e (269.9 mg, 1.0 mmol), Fe(NO3)3·9H2O (32.3 mg, 0.08 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (32.1 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5e (200.1 mg and 23.2 mg (90% purity), 74%) (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 3 / 1).

[0053] 1 H NMR (400 MHz, CDCl3): δ = 3.67 (s, 3H, OCH3), 3.18 (t, J = 7.0 Hz, 2H, CH2), 2.30 (t, J = 7.6 Hz, 2H, CH2), 1.82 (quint, J = 7.1 Hz, 2H, CH2), 1.68 - 1.56 (m, 2H, CH2), 1.45 - 1.35 (m, 2H, CH2), 1.31 (s, 6H, 3xCH2); 13 C NMR (100 MHz, 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, 1169 cm -1 ; MS(ESI) m / z: 299 (M + H) + , 321 (M + Na) + .

[0054] Example 6

[0055]

[0056] Step II: Add Fe(NO3)3·9H2O (32.6 mg, 0.08 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), 1f (146.0 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) into a 50 mL round-bottom flask in sequence. Insert an oxygen balloon, and the reaction is stirred in an oil bath at 50 °C for 48 hours. The reaction solution is passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), the solvent is removed by rotary evaporation, 2 mL of THF and 0.5 mL of HCl (3 M) are added to the crude product, and it is stirred vigorously for 2 h. The pH of the reaction solution is adjusted to about 8 with saturated sodium bicarbonate solution, 2 mL of saturated sodium bisulfite solution is added, and it is stirred vigorously for 2 h. The reaction solution is extracted with DCM (3 x 15 mL), the organic phases are combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent is removed by rotary evaporation, and it is separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1 to 10 / 1) to obtain the product 5f as a pale yellow liquid (88.6 mg, 49%, 96% purity).

[0057] 1 H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H, OCH3), 3.46 (q, J = 6.9 Hz, 2H, OCH2), 3.41 (t, J = 6.6 Hz, 2H, OCH2), 2.32 (t, J = 7.6 Hz, 2H, CH2), 1.73 - 1.52 (m, 4H, 2xCH2), 1.46 - 1.32 (m, 2H, CH2), 1.19 (t, J = 7.0 Hz, 3H, CH3); 13 C NMR (100 MHz, 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, 1109 cm -1 ; MS (ESI) m / z: 175 (M+H) + , 197 (M+Na) + ; HRMS calcd m / z for C9H 19 O3 [M+H] + : 175.1329, found 175.1330.

[0058] Example 7

[0059]

[0060] Step III: Add Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (31.9 mg, 0.1 mmol), 1 g (236.7 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) successively into a 50 mL round-bottom flask. Insert an oxygen balloon and stir the reaction in an oil bath at 50 °C for 48 hours. Filter the reaction solution through a short silica gel column (3 cm) and elute with ether (3 x 25 mL). Rotavapor to remove the solvent. Purify the crude product by silica gel column chromatography (eluent: for the first column passing: petroleum ether / ethyl acetate = 40 / 1; for the impure part's second column passing: petroleum ether / ethyl acetate = 50 / 1) to obtain 5 g (166.4 mg, 63%) of the product as a pale yellow liquid.

[0061] 1 1H NMR (400 MHz, CDCl3): δ = 7.32 - 7.20 (m, 2H, Ar-H), 6.96 - 6.83 (m, 3H, Ar-H), 3.93 (t, J = 6.6 Hz, 2H, OCH2), 3.65 (s, 3H, OCH3), 2.29 (t, J = 7.6 Hz, 2H, CH2), 1.76 (quint, J = 7.0 Hz, 2H, CH2), 1.62 (quint, J = 7.3 Hz, 2H, CH2), 1.52 - 1.40 (m, 2H, CH2), 1.38 - 1.27 (m, 6H, 3xCH2); 13 13C NMR (100 MHz, 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, 1169 cm -1 ; MS (ESI) m / z: 266 (M + H) + , 288 (M + Na) + ; HRMS calcd m / z for C 16 H 25 O3 [M + H] + : 266.1798, found 266.1796.

[0062] Example 8

[0063]

[0064] The operation was the same as that in Step II of Example 6 of the present invention. 1h (196.7 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.2 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5h (106.3 mg, 47%) (eluent: petroleum ether / ethyl acetate = 3 / 1 to 2 / 1).

[0065] 1 1H NMR (400 MHz, CDCl3): δ = 4.23 (t, J = 6.4 Hz, 2H, OCH2), 3.67 (s, 3H, OCH3), 3.01 (s, 3H, CH3), 2.34 (t, J = 7.4 Hz, 2H, CH2),1.82 - 1.73 (m, 2H, CH2), 1.72 - 1.62 (m, 2H, CH2), 1.50 - 1.39 (m, 2H, CH2); 13 13C NMR (100 MHz, 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, 1104 cm -1 ; MS (ESI) m / z: 225 (M+H) + , 247 (M+Na) + .

[0066] Example 9

[0067]

[0068] The operation was the same as that in Step I of Example 1 of the present invention. 1i (300.5 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (8.4 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5i (230.1 mg, 70%) (eluent: petroleum ether / ethyl acetate = 15 / 1 to 10 / 1).

[0069] 11H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.0 Hz, 2H, Ar-H), 7.35 (d, J = 7.6 Hz, 2H, Ar-H), 4.01 (d, J = 6.4 Hz, 2H, CH2), 3.66 (s, 3H, OCH3), 2.45 (s, 3H, CH3), 2.28 (d, J = 7.6 Hz, 2H, CH2), 1.68 - 1.50 (m, 4H, 2xCH2), 1.34 - 1.18 (m, 6H, 3xCH2); 13 13C NMR (100 MHz, 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, 1048 cm -1 ; MS (70 eV, EI) m / z (%): 328 (M + , 7.42), 91 (100); HRMS calcd m / z for C 16 H 24 O5S [M] + : 328.1339, Found: 328.1339.

[0070] Example 10

[0071]

[0072] The operation was the same as in Step II of Example 6 of the present invention. 1j (189.1 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.3 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5j (144.7 mg, 67%) (eluent: petroleum ether / ethyl acetate = 15 / 1 to 10 / 1).

[0073] 11H NMR (400 MHz, CDCl3): δ = 4.05 (t, J = 6.8 Hz, 2H, OCH2), 3.67 (s, 3H, OCH3), 2.31 (t, J = 7.4 Hz, 2H, CH2), 2.04 (s, 3H, CH3), 1.70 - 1.56 (m, 4H, 2xCH2), 1.43 - 1.28 (m, 6H, 3xCH2); 13 13C NMR (100 MHz, 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, 1034 cm -1 ; MS (ESI) m / z: 217 (M+H) + , 239 (M+Na) + ; HRMS calcd m / z for C 11 H 21 O4 [M+H] + : 217.1434, found 217.1429.

[0074] Example 11

[0075]

[0076] The operation was the same as in Step II of Example 6 of the present invention. 1k (220.1 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (31.0 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5k (164.3 mg, 66%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0077] 1 1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 7.2 Hz, 2H, Ar-H), 7.54 (t, J = 7.4 Hz, 1H, Ar-H), 7.43 (t, J = 7.6 Hz, 2H, Ar-H), 4.32 (t, J = 6.6 Hz, 2H, OCH2), 3.66 (s, 3H, OCH3), 2.34 (t, J = 7.4 Hz, 2H, CH2), 1.79 (quint, J = 7.1 Hz, 2H, CH2), 1.71 (quint, J = 7.7 Hz, 2H, CH2), 1.54 - 1.42 (m, 2H, CH2);13 13C NMR (100 MHz, 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): ν = 2951, 1735, 1715, 1451, 1436, 1271, 1171, 1114 cm -1 ; MS (70 eV, EI) m / z (%): 250 (M + , 1.09), 105 (100); HRMS calcd m / z for C 14 H 18 O4 [M] + : 250.1200, Found: 250.1204.

[0078] Example 12

[0079]

[0080] The operation was the same as in Step I of Example 1 of the present invention. 1l (146.3 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.4 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5l (116.3 mg, 67%) (eluent: petroleum ether / dichloromethane = 2 / 1 to 1 / 1, then dichloromethane).

[0081] 1 1H NMR (400 MHz, CDCl3): δ = 3.56 (s, 6H, 2xOCH3), 2.27 - 2.13 (m, 4H, 2xCH2), 1.60 - 1.47 (m, 4H, 2xCH2); 13 13C NMR (100 MHz, CDCl3) δ = 173.7, 51.5, 33.6, 24.3; IR (neat) ν = 2955, 1734, 1437, 1367, 1248, 1197, 1171, 1083 cm -1 ; MS (70 eV, EI) m / z (%): 143 ((M - OMe) + , 73.02), 114 (100).

[0082] Example 13

[0083]

[0084] The operation was the same as that in Step II of Example 6 of the present invention. 1m (160.7 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (32.0 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5m (110.3 mg, 58%) (eluent: petroleum ether / ethyl acetate = 20 / 1 to 10 / 1).

[0085] 1 1H NMR (400 MHz, CDCl3): δ = 4.13 (q, J = 7.1 Hz, 2H, OCH2), 3.67 (s, 3H, OCH3), 2.40 - 2.26 (m, 4H, 2xCH2), 1.73 - 1.58 (m, 4H, 2xCH2), 1.26 (t, J = 7.2 Hz, 3H, CH3); 13 13C NMR (100 MHz, 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, 1143 cm -1 ; MS (ESI) m / z: 189 (M + H) + , 211 (M + Na) + .

[0086] Example 14

[0087]

[0088] The operation was the same as that in Step II of Example 6 of the present invention. 1n (223.8 mg, 1.0 mmol), Fe(NO3)3·9H2O (32.3 mg, 0.08 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5n (157.9 mg, 63%) (eluent: petroleum ether / ethyl acetate = 25 / 1 to 20 / 1).

[0089] 11H NMR (400 MHz, CDCl3): δ = 7.44 - 7.25 (m, 5H, Ar-H), 5.11 (s, 2H, OCH2), 3.65 (s, 3H, OCH3), 2.37 (t, J = 7.0 Hz, 2H, CH2), 2.32 (t, J = 7.0 Hz, 2H, CH2), 1.76 - 1.58 (m, 4H, 2xCH2); 13 13C NMR (100 MHz, 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, 1140 cm -1 ; MS (ESI) m / z: 251 (M+H) + , 273 (M+Na) + .

[0090] Example 15

[0091]

[0092] The operation was the same as in Step II of Example 6 of the present invention. 1o (165.1 mg, 95% purity, 1.0 mmol), Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.5 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5o (118.6 mg, 63%, 98% purity) (eluent: petroleum ether / ethyl acetate = 60 / 1 to 50 / 1).

[0093] 1 1H NMR (400 MHz, 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 = 7.4 Hz, 2H, CH2), 2.04 (q, J = 6.9 Hz, 2H, CH2), 1.67 - 1.57 (m, 2H, CH2), 1.42 - 1.25 (m, 8H, 4xCH2); 13CNMR (100 MHz, 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, 1169 cm -1 ; MS (ESI) m / z: 185 (M+H) + .

[0094] Example 16

[0095]

[0096] The operation was the same as in Step II of Example 6 of the present invention. 1p (171.3 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.4 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.3 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a yellow liquid 5p (115.9 mg, 56%, 96% purity) (eluent: petroleum ether / ethyl acetate = 50 / 1).

[0097] 1 1H NMR (400 MHz, 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 = 7.4 Hz, 2H, CH2), 2.10 - 1.97 (m, 2H, CH2), 1.67 - 1.57 (m, 2H, CH2), 1.42 - 1.20 (m, 10H, 5xCH2); 13 13C NMR (100 MHz, 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, 1170 cm -1 ; MS (ESI) m / z: 199 (M+H) + .

[0098] Example 17

[0099]

[0100] The operation was the same as that in Step II of Example 6 of the present invention. 1q (126.9 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5q (103.9 mg, 66%, 98% purity) (eluent: petroleum ether / ethyl acetate = 30 / 1).

[0101] 1 1H NMR (400 MHz, CDCl3): δ = 3.67 (s, 3H, OCH3), 2.30 (t, J = 7.6 Hz, 2H, CH2), 2.20 (td, J1 = 7.0 Hz, J2 = 2.7 Hz, 2H, CH2), 1.95 (t, J = 2.6 Hz, 1H, CH), 1.65 (quint, J = 7.5 Hz, 2H, CH2), 1.60 - 1.50 (m, 2H, CH2), 1.48 - 1.38 (m, 2H, CH2); 13 13C NMR (100 MHz, 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, 1172 cm -1 ; MS (ESI) m / z: 155 (M + H) + .

[0102] Example 18

[0103]

[0104] The operation was the same as that in Step I of Example 1 of the present invention. 1r (167.8 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (32.1 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5r (127.6 mg, 65%) (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 2 / 1).

[0105] 11H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H, OCH3), 2.30 (t, J = 7.4 Hz, 2H, CH2), 2.17 (t, J = 7.0 Hz, 2H, CH2), 1.94 (s, 1H, CH), 1.68 - 1.57 (m, 2H, CH2), 1.52 (quint, J = 7.2 Hz, 2H, CH2), 1.45 - 1.24 (m, 8H, 4xCH2); 13 13C NMR (100 MHz, 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, 1170 cm -1 ; MS (ESI) m / z: 197 (M + H) + , 219 (M + Na) + .

[0106] Example 19

[0107]

[0108] The operation was the same as in Step I of Example 1 of the present invention. 1s (126.0 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.9 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (31.7 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5s (85.3 mg, 55%) (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 2 / 1).

[0109] 1 1H NMR (400 MHz, CDCl3): δ = 3.67 (s, 3H, OCH3), 2.33 (t, J = 7.6 Hz, 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); 13 13C NMR (100 MHz, CDCl3): δ = 173.9, 78.5, 75.7, 51.3, 33.5, 28.3, 24.0, 18.3, 3.3.

[0110] Example 20

[0111]

[0112] The operation was the same as that in Step II of Example 6 of the present invention. 1t (189.1 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (16.2 mg, 0.1 mmol), BiCl3 (31.5 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5t (90.7 mg, 41%, 98% purity) (eluent: petroleum ether / ethyl acetate = 50 / 1).

[0113] 1 1H NMR (400 MHz, 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 = 7.0 Hz, 2H, CH2), 2.37 (t, J = 7.4 Hz, 2H, CH2), 1.87 - 1.75 (m, 2H, CH2), 1.69 - 1.59 (m, 2H, CH2); 13 13C NMR (100 MHz, 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): ν = 2949, 1735, 1490, 1437, 1362, 1199, 1171, 1145 cm -1 ; MS (70 eV, EI) m / z (%): 216 (M + , 28.56), 115 (100).

[0114] Example 21

[0115]

[0116] The operation was the same as that in Step II of Example 6 of the present invention. 1u (182.7 mg, 1.0 mmol), Fe(NO3)3·9H2O (31.9 mg, 0.08 mmol), TEMPO (12.7 mg, 0.08 mmol), BiCl3 (31.5 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5u (108.3 mg, 51%) (eluent: petroleum ether / ethyl acetate = 15 / 1).

[0117] 11H NMR (400 MHz, CDCl3): δ = 4.13 (d, J = 2.4 Hz, 2H, OCH2), 3.66 (s, 3H, OCH3), 3.50 (t, J = 6.4 Hz, 2H, OCH2), 2.43 (t, J = 2.4 Hz, 1H, CH), 2.30 (t, J = 7.4 Hz, 2H, CH2), 1.70 - 1.52 (m, 4H, 2xCH2), 1.42 - 1.26 (m, 6H, 3xCH2); 13 13C NMR (100 MHz, 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, 1098 cm -1 ; MS (ESI) m / z: 213 (M+H) + , 235 (M+Na) + ; HRMS calcd m / z for C 12 H 21 O3 [M+H] + : 213.1485, found 213.1484.

[0118] Example 22

[0119]

[0120] The operation was the same as in Step II of Example 6 of the present invention. 1v (233.0 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.4 mg, 0.06 mmol), TEMPO (8.3 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5v (129.9 mg, 50%) (eluent: petroleum ether / ethyl acetate = 10 / 1 to 5 / 1).

[0121] 11H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 8.0 Hz, 2H, Ar-H), 7.44 (d, J = 8.0 Hz, 2H, Ar-H), 4.55 (s, 2H, OCH2), 3.67 (s, 3H, OCH3), 3.51 (t, J = 6.4 Hz, 2H, OCH2), 2.33 (t, J = 7.4 Hz, 2H, CH2), 1.78 - 1.58 (m, 4H, 2xCH2), 1.52 - 1.34 (m, 2H, CH2); 13 13C NMR (100 MHz, 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, 1099 cm -1 ; MS (70 eV, EI) m / z (%): 261 (M + , 3.52), 116 (100); HRMS calcd m / z for C 15 H 19 NO3 [M] + : 261.1359, Found: 261.1363.

[0122] Example 23

[0123]

[0124] The operation was the same as in Step I of Example 1 of the present invention. 1w (290.2 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5w (248.2 mg, 78%) (eluent: petroleum ether / dichloromethane = 3 / 1 to 1 / 1, then 1 / 2).

[0125] 11H NMR (400 MHz, CDCl3): δ = 7.91 - 7.78 (m, 2H, Ar-H), 7.77 - 7.65 (m, 2H, Ar-H), 3.76 - 3.55 (m, 5H, OCH3 and NCH2), 2.29 (t, J = 7.4 Hz, 2H, CH2), 1.78 - 1.55 (m, 4H, 2xCH2), 1.40 - 1.19 (m, 8H, 4xCH2); 13 13C NMR (100 MHz, 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, 1060 cm -1 ; MS (70 eV, EI) m / z (%): 317 (M + , 9.61), 160 (100); HRMS calcd m / z for C 18 H 23 NO4[M] + : 317.1622, Found: 317.1623.

[0126] Example 24

[0127]

[0128] The operation was the same as in Step II of Example 6 of the present invention. 1x (141.7 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (8.4 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a yellow liquid 5x (122.0 mg, 73%) (eluent: petroleum ether / ethyl acetate = 100 / 1 to 50 / 1).

[0129] 1 1H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H, OCH3), 2.32 (t, J = 7.8 Hz, 2H, CH2), 1.77 - 1.59 (m, 5H, CH and 2xCH2), 1.52 (q, J = 7.5 Hz, 2H, CH2), 1.30 - 1.10 (m, 4H, 2xCH2), 0.96 - 0.82 (m, 2H, 2xCH2); 1313C NMR (100 MHz, 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, 1165 cm -1 ; MS (70 eV, EI) m / z (%): 170 (M + , 1.01), 97 (100).

[0130] Example 25

[0131]

[0132] The operation was the same as in Step I of Example 1 of the present invention. 1y (136.3 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.3 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5y (105.1 mg, 64%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0133] 1 1H NMR (400 MHz, 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 = 8.0 Hz, 2H, CH2), 2.63 (t, J = 7.8 Hz, 2H, CH2); 13 13C NMR (100 MHz, 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, 1028 cm -1 ; MS (70 eV, EI) m / z (%): 164 (M + , 38.9), 104 (100).

[0134] Example 26

[0135]

[0136] The operation was the same as in Step I of Example 1 of the present invention. 1z (149.5 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.9 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5z (115.6 mg, 63%, 96% purity) (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 2 / 1).

[0137] 1 1H NMR (400 MHz, CDCl3): δ = 7.26 (t, J = 7.4 Hz, 2H, Ar-H), 7.17 (t, J = 7.4 Hz, 3H, Ar-H), 3.64 (s, 3H, OCH3), 2.64 (t, J = 7.6 Hz, 2H, CH2), 2.31 (t, J = 7.6 Hz, 2H, CH2), 2.31 (quint, J = 7.5 Hz, 2H, CH2); 13 13C NMR (100 MHz, 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, 1146 cm -1 ; MS (70 eV, EI) m / z (%): 178 (M + , 42.91), 104 (100).

[0138] Example 27

[0139]

[0140] The operation was the same as in Step I of Example 1 of the present invention. 1aa (167.5 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (32.1 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5aa (111.8 mg, 59%) (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 2 / 1).

[0141] 11H NMR (400 MHz, CDCl3): δ = 7.26 (t, J = 7.4 Hz, 2H, Ar-H), 7.20 - 7.12 (m, 3H, Ar-H), 3.65 (s, 3H, OCH3), 2.62 (t, J = 6.6 Hz, 2H, CH2), 2.32 (t, J = 6.6 Hz, 2H, CH2), 1.74 - 1.55 (m, 4H, 2xCH2); 13 13C NMR (100 MHz, 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, 1142 cm -1 ; MS (70 eV, EI) m / z (%): 192 (M + , 3.56), 91 (100).

[0142] Example 28

[0143]

[0144] The operation was the same as in Step I of Example 1 of the present invention. 1ab (182.8 mg, 97% purity, 1.0 mmol), Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.3 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were reacted for 48 hours to obtain a pale yellow liquid 5ab (162.6 mg, 79%) (eluent: petroleum ether / dichloromethane = 15 / 1 to 5 / 1, then 3 / 1).

[0145] 1 1H NMR (400 MHz, CDCl3): δ = 7.25 (t, J = 7.2 Hz, 2H, Ar-H), 7.20 - 7.09 (m, 3H, Ar-H), 3.64 (s, 3H, OCH3), 2.59 (t, J = 7.6 Hz, 2H, CH2), 2.28 (t, J = 7.6 Hz, 2H, CH2), 1.64 (sextet, J = 7.9 Hz, 4H, 2xCH2), 1.35 (quint, J = 7.6 Hz, 2H, CH2); 13CNMR(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).

[0146] Example 29

[0147]

[0148] The operation was the same as in Step II of Example 6 of the present invention. 1ac (204.1 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.3 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), MeOH (162 μL, 4 mmol), and DCE (4 mL) were reacted for 48 hours to obtain a yellow liquid 5ac (121.8 mg, 51%, 98% purity) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0149] 1 H 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); 13 C 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; 19 F 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).

[0150] Example 30

[0151]

[0152] The operation was the same as that in Step II of Example 6 of the present invention. 1ad (161.1 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.3 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (4 mL) were reacted for 60 hours to obtain a yellow liquid 5ad (89.7 mg, 47%) (eluent: petroleum ether / ethyl acetate = 10 / 1 to 8 / 1).

[0153] 1 H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8.4 Hz, 2H, Ar-H), 7.32 (d, J = 8.4 Hz, 2H, Ar-H), 3.67 (s, 3H, OCH3), 3.02 (t, J = 7.6 Hz, 2H, CH2), 2.66 (t, J = 7.6 Hz, 2H, CH2); 13 C NMR (100 MHz, 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, 1159 cm -1 ; MS (70 eV, EI) m / z (%): 189 (M + , 21.63), 129 (100).

[0154] Example 31

[0155]

[0156] The operation was the same as that in Step II of Example 6 of the present invention. 1ae (181.1 mg, 1.0 mmol), Fe(NO3)3·9H2O (33.0 mg, 0.08 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (31.7 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), and DCE (4 mL) were reacted for 48 hours to obtain a yellow liquid 5ae (89.0 mg, 43%) (eluent: petroleum ether / ethyl acetate = 8 / 1 to 5 / 1).

[0157] 11H NMR (400 MHz, CDCl3): δ = 8.15 (d, J = 8.4 Hz, 2H, Ar-H), 7.38 (d, J = 8.4 Hz, 2H, Ar-H), 3.68 (s, 3H, OCH3), 3.07 (t, J = 7.4 Hz, 2H, CH2), 2.69 (t, J = 7.4 Hz, 2H, CH2); 13 13C NMR (100 MHz, CDCl3): δ = 172.5, 148.2, 146.6, 129.1, 123.7, 51.7, 34.7, 30.5; IR (neat): ν = 3113, 3083, 1727, 1607, 1514, 1430, 1346, 1191, 1169 cm -1 ; MS (70 eV, EI) m / z (%): 209 (M + , 26.18), 149 (100).

[0158] Example 32

[0159]

[0160] The operation was the same as in Step II of Example 6 of the present invention. 1af (169.9 mg, 1.0 mmol), Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (4 mL) were reacted for 48 hours to obtain a yellow liquid 5af (103.2 mg, 52%) (eluent: petroleum ether / ethyl acetate = 25 / 1 to 20 / 1).

[0161] 1 1H NMR (400 MHz, 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 = 7.6 Hz, 2H, CH2), 2.60 (t, J = 7.8 Hz, 2H, CH2); 13 13C NMR (100 MHz, CDCl3): δ = 173.0, 138.9, 132.0, 129.6, 128.5, 51.6, 35.4, 30.2; IR (neat): ν = 2951, 1734, 1492, 1436, 1364, 1195, 1157, 1092 cm -1 ; MS (70 eV, EI) m / z (%): 200 (M( 37 Cl) + , 9.7), 198 (M(35 Cl) + ,29.17),138(100).

[0162] Example 33

[0163]

[0164] The operation was the same as in Step II of Example 6 of the present invention. 1ag (175.5 mg, 95% purity, 1.0 mmol), Fe(NO3)3·9H2O (32.3 mg, 0.08 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (32.0 mg, 0.1 mmol), MeOH (202 μL, 5 mmol), DCE (4 mL) were reacted for 48 hours to obtain a yellow liquid 5ag (107.3 mg, 55%) (eluent: petroleum ether / ethyl acetate = 15 / 1 to 10 / 1).

[0165] 1 1H NMR (400 MHz, CDCl3): δ = 7.10 (d, J = 8.8 Hz, 2H, Ar-H), 6.82 (d, J = 8.4 Hz, 2H, Ar-H), 3.76 (s, 3H, OCH3), 3.65 (s, 3H, OCH3), 2.88 (t, J = 7.8 Hz, 2H, CH2), 2.59 (t, J = 7.8 Hz, 2H, CH2); 13 13C NMR (100 MHz, 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, 1157 cm -1 ; MS (70 eV, EI) m / z (%): 194 (M + ,21.47),121(100).

[0166] Example 34

[0167]

[0168] The operation was the same as that in Step I of Example 1 of the present invention. 1a (2.4195 g, 10.0 mmol), Fe(NO3)3·9H2O (244.8 mg, 0.6 mmol), TEMPO (79.1 mg, 0.5 mmol), BiCl3 (313.3 mg, 1.0 mmol), MgSO4 (702.4 mg), MeOH (1.2 mL, 30 mmol), and DCE (30 mL) were reacted for 48 hours to obtain a white solid 5a (2.1826 mg, 81%) (eluent: petroleum ether / ethyl acetate = 200 / 1 to 80 / 1).

[0169] 1 H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H, OCH3), 2.30 (t, J = 7.4 Hz, 2H, CH2), 1.62 (quint, J = 7.2 Hz, 2H, CH2), 1.37 - 1.18 (m, 24H, 12xCH2), 0.88 (t, J = 6.8 Hz, 3H, CH3); 13 C NMR (100 MHz, 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.

[0170] Example 35

[0171]

[0172] The operation was the same as that in Step I of Example 1 of the present invention. 1a (10.8905 g, 45.0 mmol), Fe(NO3)3·9H2O (552.0 mg, 1.35 mmol), TEMPO (215.6 mg, 1.35 mmol), AlCl3 (605.8 mg, 4.5 mmol), MgSO4 (2.9995 g), MeOH (5.3 mL, 135 mmol), and DCE (90 mL) were reacted for 48 hours to obtain a white solid 5a (9.0110 g, 74%) (eluent: petroleum ether / dichloromethane = 5 / 1 to 4 / 1, then 3 / 1, then petroleum ether / ethyl acetate = 40 / 1).

[0173] 1 H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3H, OCH3), 2.30 (t, J = 7.4 Hz, 2H, CH2), 1.62 (quint, J = 7.2 Hz, 2H, CH2), 1.37 - 1.18 (m, 24H, 12xCH2), 0.88 (t, J = 6.8 Hz, 3H, CH3);13 13C NMR (100 MHz, 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.

[0174] Example 36

[0175]

[0176] Fe(NO3)3·9H2O (1.2246 g, 3 mmol), TEMPO (478.3 mg, 3 mmol), AlCl3 (1.3472 g, 10 mmol), 1c (22.8 mL, d = 0.833 g / mL, 100 mmol), MeOH (12.2 mL, 300 mmol), and DCE (200 mL) were successively added to a 1 L round-bottom flask. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with diethyl ether (200 mL), and the solvent was removed by rotary evaporation to obtain 5c. The crude spectrum showed a 1H NMR yield of 73%.

[0177] Example 37

[0178]

[0179] The operation was the same as in Step II of Example 6 of the present invention. 1q (631.8 mg, 5.0 mmol), Fe(NO3)3·9H2O (121.6 mg, 0.3 mmol), TEMPO (40.0 mg, 0.25 mmol), BiCl3 (157.1 mg, 1.5 mmol), MgSO4 (249.6 mg), MeOH (0.6 mL, 15 mmol), and DCE (15 mL) were reacted for 48 h to obtain a pale yellow liquid 5q (516.2 mg, 65%, 97% purity) (eluent: petroleum ether / ethyl acetate = 49 / 1 to 24 / 1).

[0180] 1 1H NMR (400 MHz, CDCl3): δ = 3.67 (s, 3H, OCH3), 2.30 (t, J = 7.4 Hz, 2H, CH2), 2.25 - 2.13 (m, 2H, CH2), 1.99 - 1.91 (m, 1H, CH), 1.65 (quint, J = 7.3 Hz, 2H, CH2), 1.55 (quint, J = 7.0 Hz, 2H, CH2), 1.50 - 1.38 (m, 2H, CH2); 1313C NMR (100 MHz, CDCl3): δ = 174.0, 84.2, 68.3, 51.4, 33.8, 28.1, 28.0, 24.3, 18.1.

[0181] Example 38

[0182] Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), 1aj (154.9 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were successively added to a 50 mL round-bottom flask. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5aj. The crude spectrum showed a 1H NMR yield of 18%, the corresponding aldehyde 3aj had a 1H NMR yield of 57%, and the dimethyl acetal 7aj had a 1H NMR yield of 33%.

[0183] Example 39

[0184]

[0185] Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), 1ak (140.9 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were successively added to a 50 mL round-bottom flask. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5ak. The crude spectrum showed a 1H NMR yield of 16%, and the corresponding aldehyde 3ak had a 1H NMR yield of 83%.

[0186] Example 40

[0187]

[0188] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (31.2 mg, 0.1 mmol), 1al (135.9 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 hours. The reaction mixture was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5al. The crude spectrum showed a 11% NMR yield, and the corresponding aldehyde 3al had a 77% NMR yield.

[0189] Example 41

[0190]

[0191] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (33.1 mg, 0.08 mmol), TEMPO (8.4 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), 1am (204.6 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 hours. The reaction mixture was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5am. The crude spectrum showed a 43% NMR yield, the corresponding aldehyde 3am had a 15% NMR yield, and the formal acetal 7am had a 17% NMR yield.

[0192] Example 42

[0193]

[0194] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), 1an (126.2 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 hours. The reaction mixture was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5an. The crude spectrum showed a 34% NMR yield, the corresponding aldehyde 3an had a 26% NMR yield, and the formal acetal 7an had a 30% NMR yield.

[0195] Example 43

[0196]

[0197] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.4 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (32.6 mg, 0.1 mmol), 1ao (138.5 mg, 1.0 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5ao. The crude spectrum showed a NMR yield of 30%, the corresponding aldehyde 3ao had a NMR yield of 46%, and the dimethyl acetal 7ao had a NMR yield of 10%.

[0198] Example 44

[0199]

[0200] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.4 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), 1ap (188.3 mg, 1.0 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5ap. The crude spectrum showed a NMR yield of 36%, the corresponding aldehyde 3ap had a NMR yield of 14%, and the dimethyl acetal 7ap had a NMR yield of 32%.

[0201] Example 45

[0202]

[0203] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (25.1 mg, 0.06 mmol), TEMPO (8.3 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), 1aq (135.9 mg, 1.0 mmol), MeOH (202 μL, 5 mmol), and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5aq. The crude spectrum showed a NMR yield of 22%, and the corresponding aldehyde 3aq had a NMR yield of 64%.

[0204] Example 46

[0205]

[0206] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.4 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), 1ar (128.2 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5ar. The crude spectrum showed a 25% NMR yield, and the corresponding aldehyde 3ar had a 5% NMR yield, and the dimethyl acetal 7ar had a 14% NMR yield.

[0207] Example 47

[0208]

[0209] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.9 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), AlCl3 (13.2 mg, 0.1 mmol), 1a (242.1 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 74% NMR yield, and the corresponding aldehyde 3a had a 16% NMR yield, and the dimethyl acetal 7a had an 8% NMR yield.

[0210] Example 48

[0211]

[0212] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), FeCl3 (16.0 mg, 0.1 mmol), 1a (242.3 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 31% NMR yield, and the corresponding aldehyde 3a had a 33% NMR yield, and the dimethyl acetal 7a had a 22% NMR yield.

[0213] Example 49

[0214]

[0215] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (25.0 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), InCl3 (21.9 mg, 0.1 mmol), 1a (242.9 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 35% NMR yield, the corresponding aldehyde 3a had a 29% NMR yield, and the dimethyl acetal 7a had a 7% NMR yield.

[0216] Example 50

[0217]

[0218] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (25.1 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), InBr3 (35.2 mg, 0.1 mmol), 1a (241.8 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 57% NMR yield, the corresponding aldehyde 3a had a 10% NMR yield, and the dimethyl acetal 7a had a 11% NMR yield.

[0219] Example 51

[0220]

[0221] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), 4-NHAc-TEMPO (10.8 mg, 0.05 mmol), BiCl3 (32.3 mg, 0.1 mmol), 1a (242.8 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 21% NMR yield, the corresponding aldehyde 3a had a 42% NMR yield, and the dimethyl acetal 7a had an 18% NMR yield.

[0222] Example 52

[0223]

[0224] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), 4-OMe-TEMPO (9.6 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), 1a (242.7 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 81%, the corresponding aldehyde 3a had a 1H NMR yield of 11%, and the dimethyl acetal 7a had a 1H NMR yield of 3%.

[0225] Example 53

[0226]

[0227] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), 4-OH-TEMPO (8.7 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), 1a (242.0 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 40%, the corresponding aldehyde 3a had a 1H NMR yield of 33%, and the dimethyl acetal 7a had a 1H NMR yield of 18%.

[0228] Example 54

[0229]

[0230] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (31.3 mg, 0.1 mmol), 1a (242.9 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and CHCl3 (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 25%, the corresponding aldehyde 3a had a 1H NMR yield of 43%, and the dimethyl acetal 7a had a 1H NMR yield of 31%.

[0231] Example 55

[0232]

[0233] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (31.5 mg, 0.1 mmol), 1a (242.4 mg, 1.0 mmol), MeOH (202 μL, 5 mmol), and toluene (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with diethyl ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 44%, the corresponding aldehyde 3a had a 1H NMR yield of 30%, and the dimethyl acetal 7a had a 1H NMR yield of 15%.

[0234] Example 56

[0235]

[0236] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.7 mg, 0.1 mmol), 1a (242.0 mg, 1.0 mmol), MeOH (202 μL, 5 mmol), and 1,4-dioxane (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with diethyl ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 21%, the corresponding aldehyde 3a had a 1H NMR yield of 20%, and the dimethyl acetal 7a had a 1H NMR yield of 1%.

[0237] Example 57

[0238]

[0239] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.4 mg, 0.06 mmol), TEMPO (8.1 mg, 0.05 mmol), BiCl3 (31.9 mg, 0.1 mmol), 1a (242.7 mg, 1.0 mmol), MeOH (122 μL, 3 mmol), and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with diethyl ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 65%, the corresponding aldehyde 3a had a 1H NMR yield of 26%, and the dimethyl acetal 7a had a 1H NMR yield of 3%.

[0240] Example 58

[0241]

[0242] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (31.8 mg, 0.1 mmol), 1a (242.7 mg, 1.0 mmol), MeOH (162 μL, 4 mmol) and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 71%, the corresponding aldehyde 3a had a NMR yield of 22%, and the dimethyl acetal 7a had a NMR yield of 5%.

[0243] Example 59

[0244]

[0245] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (32.6 mg, 0.1 mmol), 1a (242.1 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 74%, the corresponding aldehyde 3a had a NMR yield of 14%, and the dimethyl acetal 7a had a NMR yield of 8%.

[0246] Example 60

[0247]

[0248] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), 1a (242.5 mg, 1.0 mmol), MeOH (244 μL, 6 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 75%, the corresponding aldehyde 3a had a NMR yield of 15%, and the dimethyl acetal 7a had a NMR yield of 7%.

[0249] Example 61

[0250]

[0251] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), 1a (242.5 mg, 1.0 mmol), MeOH (284 μL, 7 mmol) and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 74%, the corresponding aldehyde 3a had a NMR yield of 15%, and the formaldehyde acetal 7a had a NMR yield of 10%.

[0252] Example 62

[0253]

[0254] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.8 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (31.5 mg, 0.1 mmol), 1a (242.4 mg, 1.0 mmol), MeOH (324 μL, 8 mmol) and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 67%, the corresponding aldehyde 3a had a NMR yield of 16%, and the formaldehyde acetal 7a had a NMR yield of 14%.

[0255] Example 63

[0256]

[0257] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (32.2 mg, 0.08 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (34.7 mg, 0.11 mmol), 1a (242.6 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 73%, the corresponding aldehyde 3a had a NMR yield of 19%, and the formaldehyde acetal 7a had a NMR yield of 6%.

[0258] Example 64

[0259]

[0260] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (28.4 mg, 0.07 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (31.9 mg, 0.10 mmol), 1a (241.6 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 76%, the corresponding aldehyde 3a had a NMR yield of 13%, and the formaldehyde acetal 7a had a NMR yield of 9%.

[0261] Example 65

[0262]

[0263] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (32.7 mg, 0.08 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (32.0 mg, 0.1 mmol), 1a (242.6 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 77%, the corresponding aldehyde 3a had a NMR yield of 14%, and the formaldehyde acetal 7a had a NMR yield of 4%.

[0264] Example 66

[0265]

[0266] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (19.0 mg, 0.06 mmol), 1a (243.0 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (4 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 40 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 64%, the corresponding aldehyde 3a had a NMR yield of 22%, and the formaldehyde acetal 7a had a NMR yield of 8%.

[0267] Example 67

[0268]

[0269] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.9 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (31.6 mg, 0.1 mmol), 1a (241.1 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 25 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 52%, the corresponding aldehyde 3a had a NMR yield of 8%, and the formaldehyde acetal 7a had a NMR yield of 25%.

[0270] Example 68

[0271]

[0272] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (31.4 mg, 0.1 mmol), 1a (241.3 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 35 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 76%, the corresponding aldehyde 3a had a NMR yield of 7%, and the formaldehyde acetal 7a had a NMR yield of 9%.

[0273] Example 69

[0274]

[0275] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.5 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (31.9 mg, 0.1 mmol), 1a (242.7 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 40 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a NMR yield of 80%, the corresponding aldehyde 3a had a NMR yield of 10%, and the formaldehyde acetal 7a had a NMR yield of 5%.

[0276] Example 70

[0277]

[0278] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.7 mg, 0.06 mmol), TEMPO (7.9 mg, 0.05 mmol), BiCl3 (32.5 mg, 0.1 mmol), 1a (242.5 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 45 °C for 48 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 81%, the corresponding aldehyde 3a had a 1H NMR yield of 11%, and the dimethyl acetal 7a had a 1H NMR yield of 7%.

[0279] Example 71

[0280]

[0281] To a 25 mL eggplant-shaped flask, Fe(NO3)3·9H2O (24.2 mg, 0.06 mmol), TEMPO (8.2 mg, 0.05 mmol), BiCl3 (31.0 mg, 0.1 mmol), 1a (241.9 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 60 °C for 48 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 56%, the corresponding aldehyde 3a had a 1H NMR yield of 31%, and the dimethyl acetal 7a had a 1H NMR yield of 5%.

[0282] Example 72

[0283]

[0284] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (8.0 mg, 0.05 mmol), BiCl3 (31.5 mg, 0.1 mmol), 1a (243.5 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An air balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 hours. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a. The crude spectrum showed a 1H NMR yield of 33%, the corresponding aldehyde 3a had a 1H NMR yield of 39%, and the dimethyl acetal 7a had a 1H NMR yield of 22%.

[0285] Example 73

[0286]

[0287] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.6 mg, 0.06 mmol), TEMPO (8.3 mg, 0.05 mmol), BiCl3 (32.3 mg, 0.1 mmol), 1a (242.0 mg, 1.0 mmol), EtOH (231.6 mg, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation to obtain 5a-A. The crude spectrum showed a NMR yield of 14%, and the corresponding aldehyde 3a had a NMR yield of 58%.

[0288] Comparative Example 1

[0289]

[0290] To a 50 mL round-bottom flask, Fe(NO3)3·9H2O (24.2 mg, 0.06 mmol), TEMPO (8.3 mg, 0.05 mmol), KCl (7.8 mg, 0.1 mmol), 1a (242.4 mg, 1.0 mmol), MeOH (202 μL, 5 mmol) and DCE (3 mL) were added successively. An oxygen balloon was inserted, and the reaction was stirred in an oil bath at 50 °C for 48 h. The reaction solution was passed through a short silica gel column (3 cm), eluted with ether (3 x 25 mL), and the solvent was removed by rotary evaporation. 2 mL of methanol and 1 mL of saturated sodium bisulfite solution were added to the crude product, and it was stirred vigorously for 1 h, dried with anhydrous sodium sulfate, passed through a short silica gel column (1 cm), eluted with DCM (3 x 15 mL), and the solvent was removed by rotary evaporation. Column chromatography on silica gel was used for separation and purification (eluent: petroleum ether / dichloromethane = 10 / 1 to 4 / 1, then 2 / 1), and the product 5a could not be obtained.

[0291] Example 74

[0292] The present invention explored the influence of alcohols on the reaction products and found that methanol had the best effect. Ethanol and n-propanol could have corresponding esterification products, but the efficiency was very low. Other alcohols could not obtain the target product 5. See Table 1 for details.

[0293] Table 1

[0294]

[0295] The protection scope of the present invention is not limited to the above examples. Without departing from the spirit and scope of the inventive concept, the changes and advantages that those skilled in the art can think of are included in the present invention, and the scope of protection is defined by the appended claims.

Claims

1. A method for directly oxidizing and esterifying alcohols with iron catalysis to prepare carboxylic acid ester compounds, characterized in that, The method directly oxidizes and esterifies the alcohol to produce a carboxylic acid ester compound by using the alcohol as a raw material, ferric nitrate nonahydrate, nitrogen oxides and Lewis acid as catalysts, and oxygen or air as an oxidant in an organic solvent under the condition of 25°C - 60°C; the alcohol is R 1 CH2OH and R 2 OH; The reaction process is shown in Reaction Formula (1): Reaction Formula (1); wherein, The said R 1 includes alkyl, alkyl with functional groups, and phenyl with functional groups; the functional group in the alkyl group with a functional group is halogen, ether bond, ester group, cycloalkyl group, aryl group, heteroaryl group, alkenyl group, alkynyl group, allene group, alkynyl group with a functional group, amino group; the functional group in the alkynyl group with a functional group is alkyl group, phenyl group; the functional group in the phenyl group with a functional group is alkoxy group, nitro group; The R 2 OH is methanol or ethanol; the Lewis acid is one or more of bismuth chloride, aluminum chloride, iron chloride, indium chloride, indium bromide, bismuth bromide, tin chloride, zinc chloride.

2. The method according to claim 1, characterized in that, Said R 1 includes an alkyl group of C1-C20, an alkyl group of C1-C20 with a functional group; the functional group in the alkyl group with a functional group is fluorine, chlorine, bromine, iodine, ether bond, ester group, alkenyl group, alkynyl group, allene group, phenyl group, p-chlorophenyl group, alkylphenyl group, m-methoxyphenyl group, alkoxynaphthyl group, biphenyl group, p-nitrophenyl group, p-cyanophenyl group, phenyl group substituted by ester group, thiophene group, amino group.

3. The method according to claim 1, wherein the nitroxide is one or more of 2,2,6,6-tetramethylpiperidine nitroxide (TEMPO), 4-acetamido-2,2,6,6-tetramethylpiperidine nitroxide (4-NHAc-TEMPO), 4-methoxy-2,2,6,6-tetramethylpiperidine nitroxide (4-OMe-TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine nitroxide (4-OH-TEMPO), 9-azabicyclo[3.3.1]nonane-N-oxy radical (ABNO).

4. The method according to claim 1, characterized in that, the organic solvent is one or a mixture of more of dichloromethane, 1,2-dichloroethane, 1,1-dichloroethane, chloroform, toluene, acetonitrile, chloroform, ethyl acetate, 1,3-dichloropropane, 1,2-dichloropropane, nitromethane, ethylene glycol dimethyl ether, dioxane.

5. The method according to claim 1, characterized in that, The raw material alcohol R 1 CH2OH and R 2 The molar ratio of OH is 1:(1 - 8).

6. The method according to claim 1, wherein The raw material alcohol R 1 The molar ratio of CH2OH, iron nitrate nonahydrate, nitrogen oxides, and Lewis acid is 100:(1-10):(1-10):(1-11).

7. The method according to claim 1, wherein The time of the reaction is 40 - 60 hours.

8. The method according to claim 1, wherein The source of oxygen for the reaction is pure oxygen or air.

9. The method according to claim 1, characterized in that The temperature of the reaction is 25°C - 60°C.

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