A method for synthesizing alcohols by in-situ catalytic alkylation

Abstract

The invention discloses an in-situ catalytic alkylation synthesis method of alcohols, which uses a VIB group metal complex, an auxiliary ligand and a base as a catalytic reaction system, uses an alcohol as an alkylating agent, and performs an in-situ catalytic alkylation reaction on a nucleophilic substrate in a solvent and an inert gas atmosphere, wherein the nucleophilic substrate is an amine. The catalytic system of the invention has a wide range of adaptability to substrates, and can catalyze the synthesis of C-N bond compounds of different structures under relatively mild conditions; a series of valuable N-alkylated compounds can be synthesized greenly.

Description

[0001] This application is a divisional application of patent application number CN202010658851.0, filed on July 9, 2020, and entitled “A method for in-situ catalytic alkylation synthesis of alcohols”. Technical Field

[0002] The invention belongs to the field of chemical synthesis, and in particular relates to an in-situ catalytic alkylation synthesis method for alcohols. Background Art

[0003] Alkylation is one of the important reactions for building CN and CC bonds, and has a wide range of applications in the synthesis of active natural products, drugs, and functional materials. Traditional N-alkylation and C-alkylation reactions require the use of highly toxic organic halogen reagents, metal organic reagents, and excessive bases, and are accompanied by the production of a large number of byproducts and waste, causing significant environmental pollution. Therefore, directly using green, renewable alcohols as alkylation reagents and adopting the "borrowing hydrogen reaction" strategy catalyzed by transition metal catalysts for alkylation reactions has great advantages in green synthesis and selectivity. This strategy uses metal catalysts to catalyze the dehydrogenation of non-activated alcohols to aldehyde / ketone electrophilic synthons; then the aldehyde / ketone reacts with a nucleophilic reagent to obtain a condensation intermediate containing an unsaturated double bond of C=N or C=C; finally, the catalyst in situ reduces the C=N or C=C double bond to form an alkylation product with a CN or CC bond. The advantages of this method are that it uses cheap and readily available alcohol substrates as alkylation reagents, has high atom efficiency, has only water as a byproduct, is environmentally friendly, can avoid over-alkylation, and has high selectivity. However, this method mainly focuses on noble metal catalysts such as ruthenium, rhodium, iridium, etc., and the cost is relatively high. In recent years, non-noble metals such as iron, cobalt, manganese, nickel and other catalysts have also been developed, but most of the non-noble metal catalysts currently used in this type of reaction contain phosphorus elements or phosphine ligands in their structures, which are environmentally unfriendly, and the applicability of the reaction substrate is also limited. Therefore, it is necessary to develop a simple, efficient, and environmentally friendly new type of non-noble metal catalyst with broad application prospects. Chromium, molybdenum, and tungsten of the VIB family are a type of non-noble metal with huge reserves on the earth, with the advantages of wide sources, low prices, and environmental friendliness. They are widely used in the fields of organic metals, battery energy storage, and luminescent metal materials. If they can be applied to the alkylation synthesis reaction of catalytic alcohols, it is very in line with the needs of sustainable development and green synthesis, and has great application value. Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings of the prior art and provide an in-situ catalytic alkylation synthesis method for alcohols which is environmentally friendly, low in cost, simple to operate and has wide applicability of reaction substrates.

[0005] The purpose of the present invention is achieved through the following technical solutions:

[0006] An in-situ catalytic alkylation synthesis method for alcohols uses a VIB group metal complex, an auxiliary ligand and a base as a catalytic reaction system, uses an alcohol (structural formula 1) as an alkylation agent, and performs an in-situ catalytic alkylation reaction on a nucleophilic substrate (structural formula 2, including amines, ketones or secondary alcohols, etc.) in a solvent and inert gas atmosphere, and the reaction temperature is 80-150°C.

[0007]

[0008] Wherein, R of the alkylating agent alcohol (Formula 1) 3 , R 4 is H, aliphatic substituent (including large steric hindrance group), aromatic substituent or heterocyclic substituent; the nucleophile (Formula 2) is an amine, a ketone or a secondary alcohol. The molar ratio of the alkylating agent to the nucleophilic substrate is 1:1 to 1.5:1, preferably 1.2:1.

[0009] The alkylating agent alcohol (Formula 1) has R 3 , R 4 In the formula, the aliphatic substituent is preferably a long-chain aliphatic hydrocarbon containing an aromatic ring; the large steric hindering group is preferably 2-methyl, 2-ethyl, 2-propyl or 2-tert-butyl; the aromatic substituent is preferably a benzene ring derivative or a heterocyclic aromatic compound, which may contain an electron-donating group, an electron-withdrawing group, or a functional group such as a cyano / alkenyl / alkynyl group, the electron-donating group is preferably an alkyl, alkoxy or thioether group, and the electron-withdrawing group is preferably a halogen or trifluoromethyl group; the heterocyclic substituent is a nitrogen-containing heterocycle, an oxygen-containing heterocycle or a sulfur-containing heterocycle. The aromatic ring-containing long-chain aliphatic hydrocarbon is preferably phenylbutyl, phenylpentyl, phenylhexyl, phenylheptyl and phenyloctyl.

[0010] More specifically, when the nucleophilic substrate is an amine, an N-alkylation reaction is performed to obtain an N-alkylated product, and the general reaction formula is:

[0011]

[0012] The amine substituent R 1 For H, R 2 It is an aliphatic substituent (including a large steric hindrance group), an aromatic substituent, a heterocyclic substituent or a sulfonyl substituent. The aliphatic substituent is preferably a long-chain aliphatic hydrocarbon containing an aromatic ring; the large steric hindrance group is preferably 2-methyl, 2-ethyl, 2-propyl or 2-tert-butyl; the aromatic substituent is preferably a benzene ring derivative or a heterocyclic aromatic compound, which may contain an electron-donating group, an electron-withdrawing group, or a functional group such as a cyano / alkenyl / alkynyl group; the electron-donating group is preferably an alkyl, alkoxy or thioether group; the electron-withdrawing group is preferably a halogen or a trifluoromethyl group; the heterocyclic substituent is a nitrogen-containing heterocyclic ring, an oxygen-containing heterocyclic ring or a sulfur-containing heterocyclic ring; the sulfonyl substituent is a p-alkylbenzenesulfonyl group. The long-chain aliphatic hydrocarbon containing an aromatic ring is preferably phenylbutyl, phenylpentyl, phenylhexyl, phenylheptyl and phenyloctyl.

[0013] More specifically, when the nucleophilic substrate is a ketone, a C-alkylation reaction is carried out to obtain a C-alkylation product, and the general reaction formula is:

[0014]

[0015] The substituent R of the ketone 1 and R 2 It is an aliphatic substituent (including a large steric hindering group), an aromatic substituent or a heterocyclic substituent. The aliphatic substituent is preferably a long-chain aliphatic hydrocarbon containing an aromatic ring; the large steric hindering group is preferably 2-methyl, 2-ethyl, 2-propyl or 2-tert-butyl; the aromatic substituent is preferably a benzene ring derivative or a heterocyclic aromatic compound, which may contain an electron-donating group, an electron-withdrawing group, or a functional group such as a cyano / alkenyl / alkynyl group, the electron-donating group is preferably an alkyl, alkoxy or thioether group, and the electron-withdrawing group is preferably a halogen or trifluoromethyl group; the heterocyclic substituent is a nitrogen-containing heterocycle, an oxygen-containing heterocycle or a sulfur-containing heterocycle. The long-chain aliphatic hydrocarbon containing an aromatic ring is preferably phenylbutyl, phenylpentyl, phenylhexyl, phenylheptyl and phenyloctyl.

[0016] More specifically, when the nucleophilic substrate is a secondary alcohol, a C-alkylation reaction is carried out to obtain a C-alkylation product, and the general reaction formula is:

[0017]

[0018] Among them, the substituent R of the secondary alcohol 1 and R 2 It is an aliphatic substituent (including a large steric hindering group), an aromatic substituent or a heterocyclic substituent. The aliphatic substituent is preferably a long-chain aliphatic hydrocarbon containing an aromatic ring; the large steric hindering group is preferably 2-methyl, 2-ethyl, 2-propyl or 2-tert-butyl; the aromatic substituent is preferably a benzene ring derivative or a heterocyclic aromatic compound, which may contain an electron-donating group, an electron-withdrawing group, or a functional group such as a cyano / alkenyl / alkynyl group, the electron-donating group is preferably an alkyl, alkoxy or thioether group, and the electron-withdrawing group is preferably a halogen or trifluoromethyl group; the heterocyclic substituent is a nitrogen-containing heterocycle, an oxygen-containing heterocycle or a sulfur-containing heterocycle. The long-chain aliphatic hydrocarbon containing an aromatic ring is preferably phenylbutyl, phenylpentyl, phenylhexyl, phenylheptyl and phenyloctyl.

[0019] The VIB group metal complex is a chromium, molybdenum or tungsten complex; preferably a zero-valent carbonyl-containing chromium, molybdenum or tungsten complex; more preferably hexacarbonyl chromium, hexacarbonyl molybdenum or hexacarbonyl tungsten.

[0020] The molar ratio of the VIB group metal complex to the nucleophilic substrate is 0.005:1 to 0.15:1, preferably 0.02:1 to 0.1:1.

[0021] The auxiliary ligand is one of the following structures L1 to L7:

[0022]

[0023] The molar ratio of the auxiliary ligand to the VIB group metal complex is 1:1 to 1.5:1, preferably 1.2:1.

[0024] The base is NaOH, KOH, NaOtBu, KOtBu, NaH or KH; the molar ratio of the base to the alkylating agent alcohol is 0.3:1 to 1.5:1, preferably 0.5:1 to 1:1.

[0025] The solvent is one or two of benzene, toluene, dioxane, THF, t-AmOH, n-hexane and cyclohexane.

[0026] The inert gas is nitrogen or argon.

[0027] The reaction time of the alkylation is 6 to 24 hours. After the reaction is completed, extraction, separation, purification and drying are performed to obtain the alkylation product.

[0028] The principle of the present invention is to successfully realize an efficient, green, in-situ simple and economical alcohol alkylation reaction by means of a hydrogen borrowing strategy and clever use of the low electronegativity of zero-valent VIB group metal complexes and the high activity of metal-hydride anion intermediates.

[0029] Compared with the prior art, the present invention has the following advantages and effects:

[0030] (1) The present invention uses a VIB group non-precious metal complex as a catalyst to provide a novel in-situ catalytic alkylation synthesis method for alcohols. The reaction directly uses alcohol as a raw material, and the reactants are easily available and green and renewable.

[0031] (2) The catalyst raw materials of the present invention are easily available, low in cost, do not require the use of phosphine-containing ligands, are low in toxicity, are environmentally friendly, and have simple reaction operations.

[0032] (3) The catalytic system of the present invention has a wide range of adaptability to substrates and can catalyze the synthesis of CN and CC bond compounds with different structures under relatively mild conditions; a series of valuable N-alkylated and C-alkylated compounds can be synthesized in a green way. DETAILED DESCRIPTION

[0033] In order to facilitate the understanding of the present invention, the present invention will be described in detail below in conjunction with specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be pointed out that, for those skilled in the art, without departing from the inventive concept, the present invention can also make some variations and improvements, which all belong to the protection scope of the present invention.

[0034] Example 1: Synthesis of N-benzylaniline

[0035] Aniline (1 eq.), benzyl alcohol (1.2 eq.), hexacarbonyl tungsten (10% eq.), auxiliary ligand L4 (R 5 =H,R 6 =H, 12% eq.), KO t Bu (1 eq.), 1,4-dixoane (2 mL), react at 130°C for 24 h. After the reaction is complete, extract with ethyl acetate, spin dry, column chromatography, and dry to obtain colorless oily N-benzylaniline with a yield of 94%.

[0036] 1 H NMR (400MHz, CDCl3) δ7.46 (q, J=7.7Hz, 4H), 7.41–7.36 (m, 1H), 7.32–7.25 (m ,2H),6.84(t,J=7.3Hz,1H),6.74(d,J=7.9Hz,2H),4.41(s,2H),4.10(s,1H). 13 C NMR (100MHz, CDCl3) δ148.05, 139.36, 129.15, 128.51, 127.38, 127.10, 117.42, 112.74, 48.16.

[0037] Example 2: Synthesis of N-benzyl-4-methylaniline

[0038] In a 10 mL Schlenk tube with a stirrer, 4-methylaniline (1 eq.), benzyl alcohol (1.2 eq.), chromium hexacarbonyl (5% eq.), auxiliary ligand L3 (R 5 =Me, X =Br, 6% eq.), KO t Bu (0.5 eq.), toluene (2 mL), react at 120°C for 24 h. After the reaction is complete, extract with ethyl acetate, spin dry, column chromatography, and dry to obtain light yellow oily N-benzyl-4-methylaniline with a yield of 95%.

[0039] 1 H NMR (400MHz, CDCl3) δ7.44–7.37(m,4H),7.32(t,J=6.8Hz,1H),7.05(d,J=8.2Hz,2H),6.62(d,J=8.4Hz,2H),4.35(s,2H),3.70(s,1H),2.30(s,3H). 13C NMR (100MHz, CDCl3) δ145.86,139.61,129.68,128.53,127.43,127.08,126.66,112.94,48.57,20.35.

[0040] Example 3: Synthesis of N-benzyl-4-methoxyaniline

[0041] In a 10 mL Schlenk tube with a stirrer, 4-methoxyaniline (1 eq.), benzyl alcohol (1.2 eq.), molybdenum hexacarbonyl (2% eq.), auxiliary ligand L1 (R 5 =Me, X =Br, 3% eq.), KO t Bu (0.5 eq.), n-hexane (2 mL), react at 130°C for 24 h. After the reaction is complete, extract with ethyl acetate, spin dry, column chromatography, and dry to obtain a light yellow oily substance, N-benzyl-4-methoxyaniline, with a yield of 97%.

[0042] 1 H NMR (400MHz, CDCl3) δ7.43–7.33(m,4H),7.29(t,J=6.8Hz,1H),6.80(d,J=8.9Hz,2H),6.63(d,J=8.9Hz,2H),4.30(s,2H),3.76(s,3H),3.42(s,1H). 13 C NMR (100MHz, CDCl3) δ152.12,142.39,139.63,128.53,127.48,127.10,114.85,114.06,55.74,49.18.

[0043] Example 4: Synthesis of N-benzyl-4-methylthioaniline

[0044] According to the synthesis method in Example 1, 4-methylthioaniline (1 eq.) was used to replace aniline. Other operating conditions were the same as in Example 1. After the reaction, a yellow oily substance, N-benzyl-4-methylthioaniline, was obtained with a yield of 88%.

[0045] 1 H NMR (400MHz, CDCl3) δ7.38–7.32(m,4H),7.31–7.27(m,1H),7.22(d,J=8.6Hz,2H),6.58(d,J=8.6Hz,2H),4.31(s,2H),4.09(s,1H),2.40(s,3H). 13C NMR (100MHz, CDCl3) δ146.89,139.08,131.35,128.57,127.34,127.20,124.35,113.38,48.18,19.01.

[0046] Example 5: Synthesis of N-benzyl-4-tert-butylaniline

[0047] According to the synthesis method in Example 2, 4-tert-butylaniline (1 eq.) was used instead of aniline. Other operating conditions were the same as in Example 2. After the reaction, a yellow oily substance, N-benzyl-4-tert-butylaniline, was obtained with a yield of 89%.

[0048] 1 H NMR (400MHz, CDCl3) δ7.40 (dt, J=14.8, 7.3Hz, 4H), 7.32 (t, J=7.0Hz, 1H), 7.26 (d, J=8.7Hz, 2H), 6.65 (d, J=8.6Hz, 2H), 4.35 (s, 2H), 3.76 (s, 1H), 1.33 (s, 9H). 13 CNMR (100MHz, CDCl3) δ145.82,140.27,139.66,128.55,127.51,127.12,125.98,112.53,48.59,33.82,31.52.

[0049] Example 6: Synthesis of N-benzyl-4-ethylaniline

[0050] According to the synthesis method in Example 3, 4-ethylaniline (1 eq.) was used instead of aniline. Other operating conditions were the same as in Example 3. After the reaction, a light yellow oily substance, N-benzyl-4-ethylaniline, was obtained with a yield of 91%.

[0051] 1 H NMR (400MHz, CDCl3) δ7.49–7.40(m,4H),7.36(t,J=6.9Hz,1H),7.12(d,J=8.4Hz,2H),6.6 8(d,J=8.4Hz,2H),4.39(s,2H),3.96(s,1H),2.65(q,J=7.6Hz,2H),1.30(t,J=7.6Hz,3H). 13 C NMR (100MHz, CDCl3) δ146.08,139.62,133.29,128.51,128.49,127.44,127.07,112.90,48.55,27.88,15.92.

[0052] Example 7: Synthesis of N-benzyl-4-bromoaniline

[0053] According to the synthesis method in Example 1, 4-bromoaniline (1 eq.) was used instead of aniline. Other operating conditions were the same as in Example 1. After the reaction, a yellow oily substance, N-benzyl-4-bromoaniline, was obtained with a yield of 91%.

[0054] 1 H NMR (400MHz, CDCl3) δ7.44–7.38(m,4H),7.37–7.33(m,1H),7.29(d,J=8.8Hz,2H),6.55(d,J=8.8Hz,2H),4.34(s,2H),4.10(s,1H). 13 C NMR (100MHz, CDCl3) δ146.97, 138.79, 131.85, 128.63, 128.19, 127.32, 114.36, 109.02, 48.14.

[0055] Example 8: Synthesis of N-benzyl-4-chloroaniline

[0056] According to the synthesis method in Example 2, 4-chloroaniline (1 eq.) was used instead of aniline. Other operating conditions were the same as in Example 2. After the reaction, a yellow oily substance, N-benzyl-4-chloroaniline, was obtained with a yield of 83%.

[0057] 1 H NMR (400 MHz, CDCl3) δ7.36 (d, J = 4.4 Hz, 4H), 7.30 (dd, J = 8.9, 4.4 Hz, 1H), 7.12 (d, J = 8.8 Hz, 2H), 6.56 (d, J = 8.8 Hz, 2H), 4.31 (s, 2H), 4.09 (s, 1H). 13 C NMR (100MHz, CDCl3) δ146.58, 138.88, 129.03, 128.67, 127.38, 127.34, 122.08, 113.90, 48.32.

[0058] Example 9: Synthesis of N-benzyl-4-fluoroaniline

[0059] According to the synthesis method in Example 3, 4-fluoroaniline (1 eq.) was used instead of aniline. Other operating conditions were the same as in Example 3. After the reaction, a yellow oily substance, N-benzyl-4-fluoroaniline, was obtained with a yield of 87%.

[0060] 1H NMR (400MHz, CDCl3) δ7.39(dd,J=6.7,3.8Hz,4H),7.34–7.29(m,1H),6.91(t,J=8.8Hz,2H),6.58(dd,J=9.0,4.4Hz,2H),4.31(s,2H),3.70(s,1H). 13 C NMR (100MHz, CDCl3) δ155.83 (d, J = 234.9Hz), 144.40, 139.17, 128.57 (d, J = 8.7Hz) ,128.21,127.34(d,J=18.2Hz),115.60(d,J=22.3Hz),113.61(d,J=7.4Hz),48.87.

[0061] 19 F NMR (377MHz,CDCl3)δ-127.85.

[0062] Example 10: Synthesis of N-benzyl-2-methylthioaniline

[0063] According to the synthesis method in Example 1, 2-methylthioaniline (1 eq.) was used to replace aniline. Other operating conditions were the same as in Example 1. After the reaction, a light yellow oily substance, N-benzyl-2-methylthioaniline, was obtained with a yield of 90%.

[0064] 1 H NMR (400MHz, CDCl3) δ7.53–7.30(m,6H),7.20(t,J=7.7Hz,1H),6.73(t,J=7.4Hz,1H),6.65(d,J=8.1Hz,1H),5.44(s,1H),4.46(s,2H),2.40(s,3H). 13 C NMR (100MHz, CDCl3) δ148.02,139.14,133.93,129.36,128.57,127.15,127.10,119.72,117.14,110.32,47.92,18.05.

[0065] HRMS(ESI):Calculated for[C 14 H 16 NS] + 230.0998; Found 230.0997.

[0066] Example 11: Synthesis of N-benzyl-2-methylaniline

[0067] According to the synthesis method in Example 2, 2-methylaniline (1 eq.) was used instead of aniline. Other operating conditions were the same as in Example 2. After the reaction was completed, a light yellow solid N-benzyl-2-methylaniline was obtained with a yield of 90%.

[0068] 1 H NMR (400MHz, CDCl3) δ7.41 (dt, J=14.8, 7.3Hz, 4H), 7.33 (t, J=7.0Hz, 1H), 7.14 (dd, J=12.7, 7. 1Hz, 2H), 6.72 (t, J = 7.3Hz, 1H), 6.66 (d, J = 8.0Hz, 1H), 4.42 (s, 2H), 3.91 (s, 1H), 2.21 (s, 3H). 13 C NMR (100MHz, CDCl3) δ146.02,139.46,130.02,128.62,127.50,127.21,127.12,121.87,117.14,109.93,48.27,17.52.

[0069] Example 12: Synthesis of N-benzyl-2-phenylaniline

[0070] According to the synthesis method in Example 3, 2-phenylaniline (1 eq.) was used instead of aniline. Other operating conditions were the same as in Example 3. After the reaction was completed, a light yellow solid N-benzyl-2-phenylaniline was obtained with a yield of 93%.

[0071] 1 H NMR (400MHz, CDCl3) δ7.64–7.53(m,4H),7.50–7.40(m,6H),7.38–7.21(m,3 H), 6.91 (t, J = 7.4Hz, 1H), 6.79 (d, J = 8.1Hz, 1H), 4.53 (s, 1H), 4.43 (s, 2H). 13 C NMR (100MHz, CDCl3) δ144.79,139.40,130.13,129.29,128.84,128.63,128.48,128.17,127.57,127.15,126.93,117.10,110.69,48.01.

[0072] Example 13: Synthesis of N-2-methylbenzyl-2-methylthioaniline

[0073] According to the synthesis method in Example 1, 2-methylthioaniline (1 eq.) was used instead of aniline, and 2-methylbenzyl alcohol (1.2 eq.) was used instead of benzyl alcohol. The other operating conditions were the same as those in Example 1. After the reaction, a light yellow oily substance, N-2-methylbenzyl-2-methylthioaniline, was obtained with a yield of 97%.

[0074] 1 H NMR(400MHz, CDCl3)δ7.50(dd,J=7.6,1.5Hz,1H),7.39(d,J=6.7Hz,1H),7.30–7.23(m,4H),6.75(td,J =7.5, 1.1Hz, 1H), 6.67 (d, J = 8.1Hz, 1H), 5.25 (s, 1H), 4.40 (d, J = 4.6Hz, 2H), 2.45 (s, 3H), 2.39 (s, 3H). 13 C NMR (100MHz, CDCl3) δ148.14,136.64,136.09,134.00,130.34,129.43,127.80,127.27,126.09,119.63,117.06,110.14,46.15,18.90,18.09.

[0075] HRMS(ESI):Calculated for[C 15 H 18 NS] + 244.1154; Found 244.1154.

[0076] Example 14: Synthesis of N-benzyl-3-vinylaniline

[0077] According to the synthesis method in Example 2, 3-vinylaniline (1 eq.) was used instead of aniline. The other operating conditions were the same as in Example 2. After the reaction, a light yellow oily substance, N-benzyl-3-vinylaniline, was obtained with a yield of 89%.

[0078] 1 H NMR (400MHz, CDCl3) δ7.57–7.34(m,5H),7.24(t,J=7.8Hz,1H),6.92(d,J=7.6Hz,1H),6.84–6.70(m,2H),6.63 (dd,J=8.0,1.9Hz,1H),5.80(dd,J=17.6,0.8Hz,1H),5.31(dd,J=10.9,0.7Hz,1H),4.41(s,2H),4.08(s,1H). 13C NMR (100MHz, CDCl3) δ148.24,139.29,138.44,137.20,129.29,128.54,127.41,127.14,115.73,113.39,112.41,110.53,48.19.

[0079] Example 15: Synthesis of 4-(benzylamino)benzonitrile

[0080] According to the synthesis method in Example 3, 4-aminobenzonitrile (1 eq.) was used to replace aniline. The other operating conditions were the same as those in Example 3. After the reaction, a colorless oily substance 4-(benzylamino)benzonitrile was obtained with a yield of 93%.

[0081] 1 H NMR (400MHz, CDCl3) δ7.44–7.29 (m, 7H), 6.59 (d, J = 8.6Hz, 2H), 4.78 (s, 1H), 4.38 (d, J = 5.5Hz, 2H). 13 C NMR (100MHz, CDCl3) δ151.08,137.75,133.55,128.72,127.51,127.15,120.38,112.28,98.66,47.26.

[0082] Example 16: Synthesis of N-4-methylthiobenzylaniline

[0083] According to the synthesis method in Example 1, 4-methylthiobenzyl alcohol (1.2 eq.) was used instead of benzyl alcohol. Other operating conditions were the same as in Example 1. After the reaction, a light yellow oily substance, N-4-methylthiobenzyl aniline, was obtained with a yield of 96%.

[0084] 1 H NMR (400MHz, CDCl3) δ7.35–7.27(m,4H),7.21(t,J=7.8Hz,2H),6.76(t,J=7.3Hz,1H),6.65(d,J=8.2Hz,2H),4.31(s,2H),4.03(s,1H),2.50(s,3H). 13 C NMR (100MHz, CDCl3) δ147.98,137.10,136.37,129.18,127.94,126.94,117.55,112.80,47.77,15.95.

[0085] Example 17: Synthesis of N-4-methylbenzylaniline

[0086] According to the synthesis method in Example 2, 4-methylbenzyl alcohol (1.2 eq.) was used instead of benzyl alcohol. Other operating conditions were the same as in Example 2. After the reaction was completed, a light yellow solid N-4-methylbenzylaniline was obtained with a yield of 90%.

[0087] 1 H NMR (400MHz, CDCl3) δ7.38 (d, J=8.0Hz, 2H), 7.33–7.24 (m, 4H), 6.84 (t, J=7. 3Hz, 1H), 6.75 (dd, J = 8.5, 0.8Hz, 2H), 4.39 (s, 2H), 4.05 (s, 1H), 2.47 (s, 3H). 13 C NMR (100MHz, CDCl3) δ148.14,136.73,136.30,129.22,129.16,127.42,117.38,112.75,47.96,21.03.

[0088] Example 18: Synthesis of N-4-methoxybenzylaniline

[0089] According to the synthesis method in Example 3, 4-methoxybenzyl alcohol (1.2 eq.) was used instead of benzyl alcohol. Other operating conditions were the same as those in Example 3. After the reaction, a light yellow oily substance, N-4-methoxybenzyl aniline, was obtained with a yield of 94%.

[0090] 1 H NMR(400MHz, CDCl3) δ7.32(d,J=8.7Hz,2H),7.24–7.18(m,2H),6.92(d,J=8.7Hz,2H),6. 75(t,J=7.3Hz,1H),6.67(dd,J=8.6,1.0Hz,2H),4.28(s,2H),3.98(s,1H),3.83(s,3H). 13 C NMR (100MHz, CDCl3) δ158.80,148.16,131.37,129.18,128.73,117.42,113.97,112.78,55.23,47.73.

[0091] Example 19: Synthesis of N-benzyl-2-pyridineaniline

[0092] According to the synthesis method in Example 1, 2-pyridineaniline (1.0 eq.) was used instead of aniline. Other operating conditions were the same as in Example 1. After the reaction was completed, white solid N-benzyl-2-pyridineaniline was obtained with a yield of 86%.

[0093] 1H NMR(400MHz, CDCl3)δ8.07(dd,J=5.0,1.1Hz,1H),7.43–7.32(m,5H),7.30–7.24(m ,1H),6.63–6.51(m,1H),6.36(d,J=8.4Hz,1H),5.44(s,1H),4.50(d,J=5.8Hz,2H). 13 C NMR (100MHz, CDCl3) δ158.59,147.93,139.09,137.24,128.39,127.19,126.96,112.77,106.51,46.05.

[0094] Example 20: Synthesis of N-benzylquinolin-8-amine

[0095] According to the synthesis method in Example 2, 8-aminoquinoline (1.0 eq.) was used instead of aniline. The other operating conditions were the same as in Example 2. After the reaction was completed, a yellow oily substance, N-benzylquinoline-8-amine, was obtained with a yield of 79%.

[0096] 1 H NMR (400MHz, CDCl3) δ8.78 (dd, J=4.1, 1.5Hz, 1H), 8.09 (dd, J=8.3, 1.4Hz, 1H), 7.50 (d, J=7.4Hz, 2H), 7.4 4–7.37(m,4H),7.33(t,J=7.2Hz,1H),7.11(d,J=8.1Hz,1H),6.71(d,J=7.5Hz,2H),4.61(d,J=5.8Hz,2H). 13 C NMR (100MHz, CDCl3) δ146.81,144.48,139.14,138.13,135.90,128.52,127.68,127.31,127.03,121.31,114.05,105.03,47.59.

[0097] Example 21: Synthesis of N-benzyl-9H-fluorene-2-amine

[0098] According to the synthesis method in Example 3, 99H-fluorene-2-amine (1.0 eq.) was used instead of aniline. The other operating conditions were the same as those in Example 3. After the reaction, a light yellow solid N-benzyl-9H-fluorene-2-amine was obtained with a yield of 86%.

[0099] 1H NMR (400MHz, CDCl3) δ7.63 (dd, J=7.5, 1.5Hz, 1H), 7.55 (dd, J=8.0, 1.8Hz, 1H), 7.38–7.27 (m, 6H), 7.17–7.08 (m,2H),6.69(dd,J=8.0,1.5Hz,1H),6.50(s,1H),4.16(t,J=7.5Hz,1H),3.53(s,2H),3.10(d,J=7.6Hz,2H). 13 C NMR (100MHz, CDCl3) δ148.67,145.86,145.52,141.17,139.91,131.88,129.48,128. 18,126.94,126.23,124.93,124.52,120.52,118.43,114.16,111.67,48.41,40.17.

[0100] Example 22: Synthesis of 1,3-diphenyl-1-propanone

[0101] Acetophenone (1 eq.), benzyl alcohol (1.2 eq.), hexacarbonyl tungsten (5% eq.), auxiliary ligand L5 (R 5 =H, 6% eq.), NaOH (0.5 eq.), toluene (2 mL), react at 140°C for 12 h. After the reaction is complete, extract with dichloromethane, spin dry, column chromatography, and dry to obtain white solid 1,3-diphenyl-1-propanone with a yield of 93%.

[0102] 1 H NMR (400MHz, CDCl3) δ7.97(d,J=7.3Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.6Hz, 2H),7.34–7.26(m,4H),7.22(t,J=7.0Hz,1H),3.48–3.25(m,2H),3.15–2.96(m,2H). 13 C NMR (100MHz, CDCl3) δ199.20,141.24,136.80,133.02,128.56,128.48,128.38,127.99,126.09,40.41,30.09.

[0103] Example 23: Synthesis of 1-phenyl-3-p-tolyl-1-propanone

[0104] Acetophenone (1 eq.), p-methylbenzyl alcohol (1.2 eq.), chromium hexacarbonyl (3% eq.), auxiliary ligand L7 (X = Br, 3.6% eq.), KOH (0.5 eq.), and toluene (2 mL) were added to a 10 mL Schlenk tube with a stirrer under nitrogen protection, and the mixture was reacted at 140° C. for 12 h. After the reaction was complete, the mixture was extracted with dichloromethane, dried by spin drying, column chromatography, and dried to obtain 1-phenyl-3-p-tolyl-1-propanone as a white solid with a yield of 91%.

[0105] 1 H NMR (400MHz, CDCl3) δ7.97(d,J=7.2Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.6 Hz,2H),7.15(q,J=8.1Hz,4H),3.44–3.21(m,2H),3.16–2.87(m,2H),2.34(s,3H). 13 CNMR (100MHz, CDCl3) δ199.30,138.14,136.84,135.57,132.98,129.16,128.54,128.25,127.99,40.56,29.68,20.96.

[0106] Example 24: Synthesis of 3-p-methoxyphenyl-1-phenyl-1-propanone

[0107] Acetophenone (1 eq.), p-methoxybenzyl alcohol (1.2 eq.), molybdenum hexacarbonyl (2% eq.), auxiliary ligand L2 (R 5 =H,R 6 =Me, X =Br, 2.4% eq.), KOH (0.5 eq.), n-hexane (2 mL), react at 130°C for 12 h. After the reaction is complete, extract with dichloromethane, spin dry, column chromatography, and dry to obtain a white solid 3-p-methoxyphenyl-1-phenyl-1-propanone with a yield of 94%.

[0108] 1 H NMR (400MHz, CDCl3) δ7.96(d,J=7.1Hz,2H),7.56(t,J=7.4Hz,1H),7.45(t,J=7.6Hz,2H),7.18(d ,J=8.6Hz,2H),6.85(d,J=8.6Hz,2H),3.79(s,3H),3.27(t,J=7.6Hz,2H),3.02(t,J=7.6Hz,2H). 13C NMR (100MHz, CDCl3) δ199.36,157.93,136.83,133.25,132.98,129.29,128.54,127.98,113.88,55.21,40.65,29.23.

[0109] Example 25: Synthesis of 3-p-fluorophenyl-1-phenyl-1-propanone

[0110] According to the synthesis method in Example 22, 4-fluorobenzyl alcohol (1.2 eq.) was used instead of benzyl alcohol. The other operating conditions were the same as those in Example 22. After the reaction was completed, white solid 3-p-fluorophenyl-1-phenyl-1-propanone was obtained with a yield of 88%.

[0111] 1 H NMR (400MHz, CDCl3) δ7.95(d,J=7.1Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.6Hz,2H),7.2 1(dd,J=8.6,5.4Hz,2H), 6.98(t,J=8.7Hz,2H), 3.28(t,J=7.5Hz,2H), 3.05(t,J=7.5Hz,2H). 13 C NMR (100MHz, CDCl3) δ199.01,136.77,133.10,129.83,129.76,128.60,127.98,115.32,115.11,40.39,29.24. 19 FNMR (376MHz,CDCl3)δ-117.27.

[0112] Example 26: Synthesis of 3-p-chlorophenyl-1-phenyl-1-propanone

[0113] According to the synthesis method in Example 23, 4-chlorobenzyl alcohol (1.2 eq.) was used instead of p-methylbenzyl alcohol. The other operating conditions were the same as those in Example 23. After the reaction was completed, white solid 3-p-chlorophenyl-1-phenyl-1-propanone was obtained with a yield of 83%.

[0114] 1 H NMR (400MHz, CDCl3) δ7.95 (d, J = 7.1Hz, 2H), 7.56 (t, J = 7.4Hz, 1H), 7.46 (t, J = 7.6Hz, 2H) ,7.30–7.23(m,2H),7.18(d,J=8.4Hz,2H),3.28(t,J=7.5Hz,2H),3.05(t,J=7.5Hz,2H). 13C NMR (100MHz, CDCl3) δ198.83,139.70,136.71,133.14,131.84,129.79,128.61,128.56,127.98,40.11,29.35.

[0115] Example 27: Synthesis of 3-p-bromophenyl-1-phenyl-1-propanone

[0116] According to the synthesis method in Example 24, 4-chlorobenzyl alcohol (1.2 eq.) was used instead of p-methoxybenzyl alcohol. Other operating conditions were the same as those in Example 24. After the reaction was completed, white solid 3-p-chlorophenyl-1-phenyl-1-propanone was obtained with a yield of 80%.

[0117] 1 H NMR (400MHz, CDCl3) δ7.95 (d, J = 8.0Hz, 2H), 7.56 (t, J = 6.8Hz, 1H), 7.50–7.37 (m, 4H), 7.17–7.05 (m, 2H), 3.28 (t, J = 7.5Hz, 2H), 3.03 (t, J = 7.4Hz, 2H). 13 C NMR (100MHz, CDCl3) δ198.77,140.21,136.68,133.13,131.50,130.19,128.60,127.96,119.83,40.01,29.38.

[0118] Example 28: Synthesis of 3-(p-trifluoromethyl)phenyl-1-phenyl-1-propanone

[0119] According to the synthesis method in Example 24, 4-trifluoromethylbenzyl alcohol (1.2 eq.) was used instead of p-methoxybenzyl alcohol. Other operating conditions were the same as those in Example 24. After the reaction was completed, white solid 3-p-trifluoromethylphenyl-1-phenyl-1-propanone was obtained with a yield of 89%.

[0120] 1 H NMR (400MHz, CDCl3) δ7.96 (d, J=7.5Hz, 2H), 7.56 (dd, J=11.2, 7.7Hz, 3H), 7.46 (t, J=7.7Hz,2H),7.37(d,J=8.0Hz,2H),3.33(t,J=7.5Hz,2H),3.14(t,J=7.4Hz,2H). 13C NMR (100MHz, CDCl3) δ198.52,145.42,136.62,133.21,128.78,128.63,127.96,125.40,125.37,122.91,39.78,29.73. 19 F NMR (376MHz,CDCl3)δ-62.35.

[0121] Example 29: Synthesis of 3-o-trifluoromethylphenyl-1-phenyl-1-propanone

[0122] According to the synthesis method in Example 22, 2-trifluoromethylbenzyl alcohol (1.2 eq.) was used instead of benzyl alcohol. The other operating conditions were the same as those in Example 22. After the reaction was completed, white solid 3-o-trifluoromethylphenyl-1-phenyl-1-propanone was obtained with a yield of 90%.

[0123] 1 H NMR (400MHz, CDCl3) δ7.96(d,J=7.2Hz,2H),7.65(d,J=7.8Hz,1H),7.56(t,J=7.4Hz,1 H),7.52–7.43(m,3H),7.40(d,J=7.6Hz,1H),7.32(t,J=7.6Hz,1H),3.51–2.95(m,4H). 13 C NMR (100MHz, CDCl3) δ198.58,140.13,136.65,133.14,131.95,131.33,128.61,128.44,128.01,126.31,126.11,126.05,123.24,40.52,27.07. 19 F NMR (376MHz, CDCl3) δ-59.68.

[0124] Example 30: Synthesis of 3-o-methylphenyl-1-phenyl-1-propanone

[0125] According to the synthesis method in Example 23, o-methylbenzyl alcohol (1.2 eq.) was used to replace p-methylbenzyl alcohol. The other operating conditions were the same as those in Example 23. After the reaction was completed, white solid 3-o-methylphenyl-1-phenyl-1-propanone was obtained. The yield was 89%.

[0126] 1H NMR (400MHz, CDCl3) δ7.99 (d, J = 7.2Hz, 2H), 7.58 (t, J = 7.4Hz, 1H), 7.47 (t, J = 7. 6Hz,2H),7.24–7.11(m,4H),3.43–3.20(m,2H),3.15–2.94(m,2H),2.37(s,3H). 13 C NMR (100MHz, CDCl3) δ199.31,139.32,136.79,135.93,133.03,130.29,128.67,128.56,127.98,126.27,126.12,39.06,27.46,19.30.

[0127] Example 31: Synthesis of 3-(2,6-dimethyl)phenyl-1-phenyl-1-propanone

[0128] According to the synthesis method in Example 24, 2,6-dimethylbenzyl alcohol (1.2 eq.) was used instead of p-methoxybenzyl alcohol. The other operating conditions were the same as those in Example 24. After the reaction was completed, white solid 3-(2,6-dimethyl)phenyl-1-phenyl-1-propanone was obtained with a yield of 92%.

[0129] 1 H NMR (400MHz, CDCl3) δ8.03(d,J=7.8Hz,2H),7.61(t,J=7.0Hz,1H),7.51(t,J=7.7Hz,2H),7.10(s,3H),3.30–2.91(m,4H),2.41(s,6H). 13 C NMR(100MHz, CDCl3)δ199.29,137.79,136.65,136.00,132.97,128.50,128.18,127.89,125.95,37.54,23.92,19.71.HRMS(ESI)m / z calcd for C 17 H 19 O[M+H] + :239.14304,found:239.14309.

[0130] Example 32: Synthesis of 1-phenyl-3-(thiophen-2-yl)-1-propanone

[0131] According to the synthesis method in Example 22, 2-thiophene methanol (1.2 eq.) was used instead of benzyl alcohol. The other operating conditions were the same as those in Example 22. After the reaction was completed, white solid 1-phenyl-3-(thiophen-2-yl)-1-propanone was obtained with a yield of 89%.

[0132] 1 H NMR (400MHz, CDCl3) δ7.98 (d, J = 7.1Hz, 2H), 7.57 (t, J = 7.4Hz, 1H), 7.47 (t, J = 7.6Hz, 2H), 7.13 (dd, J = 5.1, 1.2Hz, 1H), 6.93 (dd, J=5.1, 3.4Hz, 1H), 6.87 (dd, J=3.3, 0.9Hz, 1H), 3.40–3.34 (m, 2H), 3.33–3.27 (m, 2H). 13 C NMR (100MHz, CDCl3) δ198.55,143.84,136.69,133.13,128.60,127.99,126.81,124.64,123.34,40.51,24.18.

[0133] Example 33: Synthesis of 1-phenyl-3-ferrocenyl-1-propanone

[0134] According to the synthesis method in Example 23, ferrocenylmethanol (1.2 eq.) was used instead of p-methylbenzyl alcohol. The other operating conditions were the same as those in Example 23. After the reaction was completed, yellow solid 1-phenyl-3-ferrocenyl-1-propanone was obtained with a yield of 89%.

[0135] 1 H NMR (400MHz, CDCl3) δ7.97(d,J=7.4Hz,2H),7.57(t,J=7.3Hz,1H),7.47(t,J=7.6Hz,2H),4.19–4.03(m,9H),3.39–3.07(m,2H),2.95–2.57(m,2H). 13 C NMR (100MHz, CDCl3) δ199.48,136.85,132.97,128.55,127.99,87.95,68.55,68.50,68.08,67.31,40.30,24.06.

[0136] Example 34: Synthesis of 3-(Furan-2-yl)-1-phenyl-1-propanone

[0137] According to the synthesis method in Example 24, 2-furanmethanol (1.2 eq.) was used instead of p-methoxybenzyl alcohol. The other operating conditions were the same as those in Example 24. After the reaction was completed, light yellow solid 3-(furan-2-yl)-1-phenyl-1-propanone was obtained with a yield of 85%.

[0138] 1H NMR (400MHz, CDCl3) δ7.72(d,J=3.7Hz,1H),7.65(d,J=4.9Hz,1H),7.38–7.21(m,5H),7.16–7.11(m,1H),3.26(t,J=7.7Hz,2H),3.13–3.06(m,2H). 13 C NMR (100MHz, CDCl3) δ192.11,144.12,140.95,133.51,131.77,128.50,128.38,128.04,126.17,41.10,30.35.

[0139] Example 35: Synthesis of 1-(2,6-dimethyl)phenyl-3-phenyl-1-propanone

[0140] According to the synthesis method in Example 22, 2,6-dimethylacetophenone (1.0 eq.) was used instead of acetophenone. The other operating conditions were the same as those in Example 22. After the reaction was completed, a light yellow oily substance 1-(2,6-dimethyl)phenyl-3-phenyl-1-propanone was obtained with a yield of 89%.

[0141] 1 H NMR (400MHz, CDCl3) δ7.29(qd,J=14.2,6.9Hz,5H),7.19(t,J=7.6Hz,1H),7.04(d,J=7.5Hz,2H),3.25–2.92(m,4H),2.20(s,6H). 13 C NMR(100MHz, CDCl3)δ209.39,142.12,140.83,132.41,128.49,128.45,128.43,127.70,126.11,46.16,29.34,18.97.HRMS(ESI)m / z calcd for C 17 H 18 ONa[M+H+Na] + :261.12499,found:261.12492.

[0142] Example 36: Synthesis of 3-phenyl-1-(2-trifluoromethyl)phenyl-1-propanone

[0143] According to the synthesis method in Example 23, 2-trifluoromethylacetophenone (1.0 eq.) was used instead of acetophenone. The other operating conditions were the same as those in Example 23. After the reaction was completed, white solid 3-phenyl-1-(2-trimethyl)phenyl-1-propanone was obtained with a yield of 82%.

[0144] 1H NMR (400MHz, CDCl3) δ7.71 (d, J = 7.0Hz, 1H), 7.61–7.51 (m, 2H), 7.35–7.28 (m, 3H), 7.27–7.19 (m, 3H), 3.23–3.15 (m, 2H), 3.10–3.02 (m, 2H). 13 C NMR (100MHz, CDCl3) δ203.38,140.58,131.78,129.96,128.51,128.34,126.79,126.67,126.62,126.21,44.83,29.81. 19 F NMR(376MHz,CDCl3)δ-58.06.HRMS(ESI)m / z calcd for C 16 H 12 OF3[MH] - :277.08457,found:277.08459.

[0145] Example 37: Synthesis of 2-benzyl-3,4-dihydro-1(2H)-naphthalenone

[0146] According to the synthesis method in Example 24, 3,4-dihydro-1(2H)-naphthalenone (1.0 eq.) was used instead of acetophenone. The other operating conditions were the same as those in Example 24. After the reaction was completed, a light yellow oily substance 2-benzyl-3,4-dihydro-1(2H)-naphthalenone was obtained with a yield of 88%.

[0147] 1 H NMR(400MHz, CDCl3)δ8.08(dd,J=7.8,1.0Hz,1H),7.47(td,J=7.5,1.4Hz,1H),7.36–7.28(m,3H),7.28–7.18(m,4H),3.50(dd,J=13.6,3.9Hz,1H ),3.03–2.85(m,2H),2.81–2.71(m,1H),2.65(dd,J=13.6,9.6Hz,1H),2.12(dq,J=13.4,4.5Hz,1H),1.80(dddd,J=13.3,11.6,10.1,5.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ199.38,144.00,140.00,133.24,132.43,129.23,128.68,128.37,127.51,126.59,126.10,49.42,35.64,28.59,27.63.

[0148] Example 38: Synthesis of 1,3-diphenyl-1-propanone

[0149] In a 10 mL Schlenk tube with a stirrer, phenylethanol (1 eq.), benzyl alcohol (1.2 eq.), hexacarbonyl tungsten (10% eq.), auxiliary ligand L4 (R 5 =H,R 6 =H, 12% eq.), KO t Bu (1 eq.), t-AmOH (2 mL), react at 130°C for 24 h. After the reaction is complete, extract with dichloromethane, spin dry, column chromatography, and dry to obtain white solid 1,3-diphenyl-1-propanone with a yield of 88%.

[0150] 1 H NMR (400MHz, CDCl3) δ7.97(d,J=7.1Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.6Hz,2H),7. 30(dd,J=14.9,7.9Hz,4H),7.21(t,J=7.0Hz,1H),3.31(t,J=7.6Hz,2H),3.10–3.06(m,2H). 13 C NMR (100MHz, CDCl3) δ199.21,141.26,136.83,133.04,128.58,128.51,128.40,128.02,126.11,40.44,30.12.

[0151] Example 39: Synthesis of 1-phenyl-3-p-methylphenyl-1-propanone

[0152] In a 10 mL Schlenk tube with a stirrer, phenylethanol (1 eq.), p-methylbenzyl alcohol (1.2 eq.), hexacarbonyl chromium (5% eq.), auxiliary ligand L7 (X = Br, 6% eq.), NaOH (0.5 eq.), t-AmOH (2 mL) were added under nitrogen protection, and the mixture was reacted at 130° C. for 24 h. After the reaction was complete, the mixture was extracted with dichloromethane, dried by spin drying, column chromatography, and dried to obtain a white solid 1-phenyl-3-p-methylphenyl-1-propanone with a yield of 86%.

[0153] 1 H NMR (400MHz, CDCl3) δ7.96(d,J=7.2Hz,2H),7.56(t,J=7.4Hz,1H),7.45(t,J=7.6Hz ,2H),7.21–7.09(m,4H),3.29(t,J=7.7Hz,2H),3.03(t,J=7.7Hz,2H),2.33(s,3H).13 C NMR (100MHz, CDCl3) δ199.32,138.17,136.88,135.61,133.00,129.18,128.57,128.27,128.02,40.60,29.71,20.99.

[0154] Example 40: Synthesis of 3-p-methoxyphenyl-1-phenyl-1-propanone

[0155] In a 10 mL Schlenk tube with a stirrer, phenylethanol (1 eq.), p-methoxybenzyl alcohol (1.2 eq.), molybdenum hexacarbonyl (3% eq.), auxiliary ligand L3 (R 5 =Me, X =Br, 3.6% eq.), NaOH (0.5 eq.), toluene (2 mL), react at 130°C for 24 h. After the reaction is complete, extract with dichloromethane, spin dry, column chromatography, and dry to obtain white solid 3-p-methoxyphenyl-1-phenyl-1-propanone with a yield of 90%.

[0156] 1 H NMR (400MHz, CDCl3) δ7.97(d,J=7.8Hz,2H),7.56(t,J=7.3Hz,1H),7.46(t,J=7.6Hz,2H),7.18(d ,J=8.4Hz,2H),6.86(d,J=8.4Hz,2H),3.79(s,3H),3.28(t,J=7.7Hz,2H),3.03(t,J=7.6Hz,2H). 13 C NMR (100MHz, CDCl3) δ199.29,157.92,136.83,133.23,132.94,129.27,128.51,127.95,113.87,55.18,40.61,29.21.

[0157] Example 41: Synthesis of 3-phenyl-1-p-trifluoromethylphenyl-1-propanone

[0158] According to the synthesis method in Example 38, 4-trifluoromethylacetophenone (1.0 eq.) was used instead of acetophenone. The other operating conditions were the same as those in Example 38. After the reaction was completed, white solid 3-phenyl-1-trifluoromethylphenyl-1-propanone was obtained with a yield of 82%.

[0159] 1H NMR (400MHz, CDCl3) δ7.96 (d, J=7.9Hz, 2H), 7.61–7.52 (m, 3H), 7.46 (t, J=7. 6Hz, 2H), 7.37 (d, J = 8.0Hz, 2H), 3.33 (t, J = 7.5Hz, 2H), 3.14 (t, J = 7.4Hz, 2H). 13 C NMR (100MHz, CDCl3) δ198.53, 145.42, 136.65, 133.21, 128.78, 128.63, 128.32, 127.97, 125.39 (q, J = 3.8Hz), 122.91, 39.78, 29.74. 19 F NMR (376MHz, CDCl3) δ-62.36.

[0160] Example 42: Synthesis of 3-p-fluorophenyl-1-phenyl-1-propanone

[0161] According to the synthesis method in Example 39, p-fluorobenzyl alcohol (1.2 eq.) was used instead of p-methylbenzyl alcohol. Other operating conditions were the same as those in Example 39. After the reaction was completed, white solid 3-p-fluorophenyl-1-phenyl-1-propanone was obtained with a yield of 86%.

[0162] 1 H NMR(400MHz, CDCl3) δ7.95(d,J=7.2Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.6Hz,2H),7.2 1(dd,J=8.5,5.5Hz,2H),6.98(t,J=8.7Hz,2H),3.28(t,J=7.6Hz,2H),3.05(t,J=7.5Hz,2H). 13 C NMR (100MHz, CDCl3) δ199.00, 133.11, 129.76 (t, J = 8.4Hz), 128.58 (d, J = 6. 8Hz),128.00,127.70,125.87,115.23(d,J=21.2Hz),114.97,40.41,29.27. 19 F NMR (376MHz,CDCl3)δ-117.29.

[0163] Example 43: Synthesis of 3-p-bromophenyl-1-phenyl-1-propanone

[0164] According to the synthesis method in Example 40, p-bromobenzyl alcohol (1.2 eq.) was used instead of p-methoxybenzyl alcohol, molybdenum hexacarbonyl (5% eq.), and auxiliary ligand L3 (R 5=Me, X=Br, 6% eq.), and other operating conditions were the same as those in Example 40. After the reaction, a white solid 3-p-bromophenyl-1-phenyl-1-propanone was obtained with a yield of 86%.

[0165] 1 H NMR (400MHz, CDCl3) δ7.95 (d, J=7.7Hz, 2H), 7.56 (t, J=7.3Hz, 1H), 7.49–7.3 8(m,4H),7.13(d,J=8.2Hz,2H),3.28(t,J=7.5Hz,2H),3.03(t,J=7.5Hz,2H). 13 C NMR (100MHz, CDCl3) δ198.73,140.21,136.68,133.11,131.49,130.18,128.59,127.95,119.83,39.99,29.38.

[0166] Example 44: Synthesis of 3-(2-methylphenyl)-1-phenyl-1-propanone

[0167] According to the synthesis method in Example 38, 2-methylbenzyl alcohol (1.2 eq.) was used instead of benzyl alcohol, and other operating conditions were the same as those in Example 38. After the reaction was completed, white solid 3-(2-methylphenyl)-1-phenyl-1-propanone was obtained with a yield of 91%.

[0168] 1 H NMR (400MHz, CDCl3) δ8.00(d,J=7.8Hz,2H),7.58(t,J=7.3Hz,1H),7.48(t,J=7. 6Hz,2H),7.24–7.12(m,4H),3.38–3.23(m,2H),3.18–3.01(m,2H),2.38(s,3H). 13 C NMR (100MHz, CDCl3) δ199.27,139.31,136.78,135.91,133.01,130.27,128.66,128.55,127.97,126.25,126.11,39.04,27.45,19.29.

[0169] Example 45: Synthesis of 3-(naphthalen-2-yl)-1-phenyl-1-propanone

[0170] According to the synthesis method in Example 39, naphthalene-2-ylmethanol (1.2 eq.) was used instead of p-methylbenzylmethanol, and the other operating conditions were the same as those in Example 39. After the reaction was completed, white solid 3-(naphthalene-2-yl)-1-phenyl-1-propanone was obtained with a yield of 88%.

[0171] 1 H NMR(400MHz, CDCl3)δ8.00(d,J=7.6Hz,2H),7.82(t,J=7.8Hz,3H),7.71(s,1H),7 .57(t,J=7.3Hz,1H),7.50–7.38(m,5H),3.41(t,J=7.6Hz,2H),3.31–3.19(m,2H). 13 C NMR (100MHz, CDCl3) δ199.10,138.74,136.80,133.58,133.04,132.05,128.57, 128.08,128.00,127.58,127.41,127.13,126.46,125.97,125.28,40.30,30.22.

[0172] Example 46: Synthesis of 1-phenyl-3-ferrocenyl-1-propanone

[0173] According to the synthesis method in Example 40, ferrocenylmethanol (1.2 eq.) was used instead of p-methoxybenzylmethanol, molybdenum hexacarbonyl (5% eq.), and the auxiliary ligand L3 (R 5 =Me, X=Br, 6% eq.), and other operating conditions were the same as those in Example 40. After the reaction, yellow solid 1-phenyl-3-ferrocenyl-1-propanone was obtained with a yield of 87%.

[0174] 1 H NMR (400MHz, CDCl3) δ7.97(d,J=7.2Hz,2H),7.56(d,J=6.9Hz,1H),7.47(t,J=6 .9Hz,2H),4.11(d,J=23.4Hz,9H),3.20(t,J=7.3Hz,2H),2.80(t,J=7.2Hz,2H). 13 CNMR(100MHz, CDCl3)δ199.43,136.83,132.94,128.52,127.96,87.93,68.48,68.06,67.29,40.27,24.03.

[0175] Example 47: Synthesis of 3-phenyl-1-trifluoromethylphenyl-1-propanone

[0176] According to the synthesis method in Example 38, m-trifluoromethylphenylethanol (1.0 eq.) was used instead of phenylethanol. Other operating conditions were the same as those in Example 38. After the reaction was completed, white solid 3-phenyl-1-m-trifluoromethylphenyl-1-propanone was obtained with a yield of 82%.

[0177] 1 H NMR (400MHz, CDCl3) δ8.19(s,1H),8.13(d,J=7.8Hz,1H),7.81(d,J=7.6Hz,1H),7.59(t,J=7. 8Hz,1H),7.34–7.29(m,2H),7.27–7.19(m,3H),3.33(t,J=7.6Hz,2H),3.09(t,J=7.5Hz,2H). 13 C NMR (100MHz, CDCl3) δ197.76,140.85,137.33,131.41,131.12,129.44(dd,J=7.1,3 .6Hz),129.28,128.93,128.58,128.40,126.28,124.87(q,J=3.7Hz),40.55,29.91. 19 F NMR (377MHz, CDCl3) δ-62.82.

[0178] Example 48: Synthesis of 1-(naphthalen-1-yl)-1-phenyl-1-propanone

[0179] According to the synthesis method in Example 39, naphthalene-1-ylethanol (1.0 eq.) was used instead of phenylethanol, and the other operating conditions were the same as those in Example 39. After the reaction was completed, white solid 1-(naphthalene-1-yl)-1-phenyl-1-propanone was obtained with a yield of 83%.

[0180] 1 H NMR (400MHz, CDCl3) δ8.55(d,J=8.4Hz,1H),7.98(d,J=8.2Hz,1H),7.88(d,J=7.8Hz,1H),7.82(d,J=7.1Hz,1H),7.56(dt,J=14.8,7.1Hz,2 H),7.47(t,J=7.7Hz,1H),7.32(dd,J=19.8,12.2Hz,2H),7.17(ddd,J=21.7,14.5,7.0Hz,3H),3.39(t,J=7.7Hz,2H),3.15(t,J=7.6Hz,2H). 13 C NMR (100MHz, CDCl3) δ203.54,141.09,135.99,133.95,132.55,130.11,129.09, 128.52,128.44,127.86,127.36,126.43,126.15,125.76,124.33,43.82,30.59.

[0181] Example 49: Synthesis of 1-phenyl-3-ferrocenyl-1-propanone

[0182] According to the synthesis method in Example 40, o-methylphenethyl alcohol (1.0 eq.) was used instead of phenethyl alcohol, molybdenum hexacarbonyl (5% eq.), and the auxiliary ligand L3 (R 5 =Me, X =Br, 6% eq.), and other operating conditions were the same as those in Example 40. After the reaction, a light yellow oily substance, 1-phenyl-3-ferrocenyl-1-propanone, was obtained with a yield of 82%.

[0183] 1 H NMR (400MHz, CDCl3) δ7.64(d,J=8.0Hz,1H),7.40(t,J=7.4Hz,1H),7.34(t,J=7.5Hz,2H) ,7.26(dd,J=17.5,6.9Hz,5H),3.27(t,J=7.6Hz,2H),3.09(t,J=7.6Hz,2H),2.52(s,3H). 13 C NMR (100MHz, CDCl3) δ203.32,141.13,138.01,137.86,131.90,131.18,128.44,128.36,128.30,126.06,125.60,43.16,30.28,21.18.

[0184] Embodiment 50

[0185] According to the synthesis method in Example 1, the auxiliary ligand L4 (R 5 =H,R 6 =H, 10% eq.), and other operating conditions were the same as those in Example 1. After the reaction, a colorless oily substance, N-benzylaniline, was obtained with a yield of 89%.

[0186] Embodiment 51

[0187] According to the synthesis method in Example 1, the auxiliary ligand L4 (R 5 =H,R 6 =H, 15% eq.), other operating conditions were the same as in Example 1, and after the reaction, a colorless oily substance N-benzylaniline was obtained with a yield of 95%.

[0188] Embodiment 52

[0189] According to the synthesis method in Example 1, hexacarbonyl tungsten (15% eq.), auxiliary ligand L4 (R 5 =H,R 6 =H, 18% eq.), other operating conditions were the same as in Example 1, and after the reaction, a colorless oily substance N-benzylaniline was obtained with a yield of 96%.

[0190] Embodiment 53

[0191] According to the synthesis method in Example 1, the amount of benzyl alcohol used was 1.0 eq., and the other operating conditions were the same as in Example 1. After the reaction was completed, a colorless oily substance, N-benzylaniline, was obtained with a yield of 86%.

[0192] Embodiment 54

[0193] According to the synthesis method in Example 1, the amount of benzyl alcohol used was 1.5 eq., and the other operating conditions were the same as in Example 1. After the reaction was completed, a yellow colorless oily substance N-benzylaniline was obtained, and the yield was 95%.

[0194] Embodiment 55

[0195] According to the synthesis method in Example 3, the amount of the metal complex molybdenum hexacarbonyl is (1% eq.), the auxiliary ligand L1 (R 5 =Me, X=Br, 1.2% eq.), and other operating conditions were the same as those in Example 3. After the reaction, a light yellow oily substance, N-benzyl-4-methoxyaniline, was obtained with a yield of 85%.

[0196] Embodiment 56

[0197] According to the synthesis method of Example 40, the amount of base NaOH used was 1.0 eq., and the other operating conditions were the same as those of Example 40. After the reaction was completed, white solid 3-p-methoxyphenyl-1-phenyl-1-propanone was obtained with a yield of 91%.

[0198] Embodiment 57

[0199] According to the synthesis method of Example 40, the amount of base NaOH used was 1.5 eq., and the other operating conditions were the same as those of Example 40. After the reaction was completed, white solid 3-p-methoxyphenyl-1-phenyl-1-propanone was obtained with a yield of 92%.

[0200] The above descriptions are merely embodiments of the present invention, but the implementation methods of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention are equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for synthesizing alcohols by in-situ catalytic alkylation, characterized in that: The catalytic reaction system is a VIB group metal complex, an auxiliary ligand and a base, and an alcohol is used as an alkylating agent. In a solvent and an inert gas atmosphere, the nucleophilic substrate is subjected to an in situ catalytic alkylation reaction. The molar ratio of the alkylating agent to the nucleophilic substrate is 1:1~1.5:1, and the reaction temperature is 80~150 o C; the nucleophilic substrate is an amine, and an N-alkylation reaction is performed to obtain an N-alkylated product, and the reaction formula is: The amine substituent R 1 For H, R 2 is an aliphatic substituent, an aromatic substituent, a heterocyclic substituent or a sulfonyl substituent; R 3 , R 4 is H, an aliphatic substituent, an aromatic substituent or a heterocyclic substituent; The aliphatic substituent is a long-chain aliphatic hydrocarbon containing an aromatic ring or a large steric hindering group; the long-chain aliphatic hydrocarbon containing an aromatic ring is phenylbutyl, phenylpentyl, phenylhexyl, phenylheptyl or phenyloctyl; the large steric hindering group is 2-methyl, 2-ethyl, 2-propyl or 2-tert-butyl; The aromatic substituent is a benzene ring containing an alkyl group, an alkoxy group, a thioether group, a halogen group, a trifluoromethyl group, a cyano group, an alkenyl group, or an alkynyl group; The heterocyclic substituent is a nitrogen-containing heterocyclic ring, an oxygen-containing heterocyclic ring or a sulfur-containing heterocyclic ring; The sulfonyl substituent is p-alkylbenzenesulfonyl; The VIB group metal complex is chromium hexacarbonyl, molybdenum hexacarbonyl or tungsten hexacarbonyl; the auxiliary ligand is one of the following structures L1 to L7: 。 2. The in-situ catalytic alkylation synthesis method of alcohols according to claim 1, characterized in that: The molar ratio of the VIB group metal complex to the nucleophilic substrate is 0.005:1 to 0.15:

1.

3. The in-situ catalytic alkylation synthesis method of alcohols according to claim 1, characterized in that: The molar ratio of the auxiliary ligand to the VIB group metal complex is 1:1 to 1.5:

1.

4. The in-situ catalytic alkylation synthesis method of alcohols according to claim 1, characterized in that: The base is NaOH, KOH, NaOtBu, KOtBu, NaH or KH; the molar ratio of the base to the alkylating agent alcohol is 0.3:1-1.5:

1.

5. The in-situ catalytic alkylation synthesis method of alcohols according to claim 1, characterized in that: The solvent is one or two of benzene, toluene, dioxane, THF, t-AmOH, n-hexane and cyclohexane.

6. The in-situ catalytic alkylation synthesis method of alcohols according to claim 1, characterized in that: The inert gas is nitrogen or argon; the reaction time of the alkylation is 6 to 24 hours. After the reaction is completed, extraction, separation, purification and drying are performed to obtain the alkylation product.

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