CN110734384B - Preparation method of hydroxyamide - Google Patents
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Abstract
A method for preparing a hydroxyamide of formula (I),
which is prepared by the homogeneous catalytic hydrogenation reaction of cyclic imide shown in a formula (II),
wherein R is 1 ，R 2 ，R 3 Independently represents H, C1-C12 alkyl, aryl or alkyl containing heteroatom substitution, aryl, R 1 ，R 2 Or C1-C12 alkyl, aryl or heteroatom-containing substituted alkyl, aryl connected by a ring. The catalyst conversion number (TON) of the invention is as high as 100,000, and compared with the prior art, the catalyst has high atom economy and is greenNo pollution, easy industrialization, etc.
Description
Technical Field
The invention relates to the field of organic chemical synthesis, in particular to a preparation method of a hydroxy amide compound.
Background
Hydroxyamides are important organic compounds. On one hand, the organic polymer can be used as a multifunctional organic synthon to carry out various organic reactions to generate fine organic chemicals with important functions. On the other hand, the structure is widely present in natural products and bioactive molecules, and is a structure of a lead compound such as a superior medicine and pesticide. Even such structures are the first-line drugs currently on the market or the pharmaceutical mother-core structures under development, such as vitamin B5, cilostamide, embodromine, etc., which have been proven to have great potential for use.
In order to obtain such compounds starting from cyclic imides, several methods have been developed and summarized in two main categories: one is the reduction of a cyclic imide compound by a metal hydride, and representative reagents are sodium borohydride, lithium borohydride and the like (Tetrahedron Letters,39(28), 5017-5018; 1998; Journal of Organic Chemistry,26,2273-6; 1961). The method needs equivalent reduction reagent, the reaction is sensitive to water, a large amount of three wastes are generated by post-treatment, and the method has no large-scale application potential. The second is a process by catalytic hydrogenation. The method has the advantages of high atom economy, few byproducts, simple post-treatment and almost no three wastes, and is an ideal method. However, the disadvantages of the prior methods are that the activity of the catalyst is too low, the dosage of the catalyst is large, the cost is high, and the requirements of industrial application cannot be met. For example, Takao Ikariya et al, using a half sandwich type ruthenium catalyst, achieved the preparation of hydroxyamides from cyclic imides at catalyst levels of 1% to 10% (Journal of the American Chemical Society,129(2), 290-.
Disclosure of Invention
The invention discloses a method for directly preparing a hydroxy amide compound by homogeneous catalytic hydrogenation of cyclic imide. Compared with the prior art, the method has the advantages of high atom economy, greenness and high efficiency, greatly reduces the three-waste amount, and is beneficial to industrial scale-up production. The chemical structure formula of the hydroxy amide compound is represented by the following general formula (I):
wherein R is 1 ，R 2 ，R 3 Independently H, C1-C12 alkyl, aryl or alkyl and aryl containing heteroatom substitution. R 1 ，R 2 Or C1-C12 alkyl, aryl or heteroatom-containing substituted alkyl, aryl connected by a ring.
The chemical reaction equation of the invention is as follows:
in the reaction formula, the compound (II) is cyclic imide, and the catalyst is an in-situ complex of a ligand and an iridium metal precursor. The structure of the ligand is ferrocene ligand with a structure (III), wherein Ar is phenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3, 5-dimethyl-4-methoxyphenyl; the iridium metal precursor is [ Ir (COD) Cl] 2 (ii) a The solvent is one of isopropanol and tetrahydrofuran or a mixture of the isopropanol and the tetrahydrofuran in any proportion, and the base is one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium hydroxide, sodium carbonate, potassium carbonate and cesium carbonate or a mixture of the tert-butoxide, the sodium carbonate, the potassium carbonate and the cesium carbonate in any proportion.
According to the invention, the tridentate ligand with strong electron donating property and iridium are adopted as the catalyst, so that on one hand, the stability of the catalyst is enhanced, the catalyst is not easy to inactivate, on the other hand, the activity of negative hydrogen in the center of the catalyst is greatly enhanced, two molecules of hydrogen can be simultaneously activated to reduce cyclic imide, and the hydroxy amide compound can be obtained through one-step reaction. The catalyst conversion number (TON) is as high as 100,000, which is far higher than the prior preparation technology of the similar compounds. Meanwhile, compared with the prior art, the method has the characteristics of high atom economy, greenness, no pollution, easy industrialization and the like.
Detailed Description
The present invention will be described in further detail with reference to the following examples, but the present invention is not limited to these examples.
Example 1
Preparation of the catalyst
In a glove box, ligand (5.5mg,0.011mmol,2.2equiv), [ Ir (COD) Cl was weighed] 2 (3.4mg,0.005mmol,1equiv), 10mL of ultra-dry isopropanol was added, and the mixture was stirred at room temperature for 1.0 hour to prepare a catalyst metal complex having a concentration of 0.001mol/L, which was used directly in the homogeneous catalytic hydrogenation.
Example 2
In a glass tube with magnetons, 237mg of 2-benzylisoindoline-1, 3-dione (1mmol), 11.2mg of potassium tert-butoxide, 5 ml of isopropanol under nitrogen protection, 200. mu.l of 0.001M catalyst (S/C. RTM. 5,000) were added, and then the reaction flask was transferred into an autoclave, which was then tightened, charged with 4MPa of hydrogen and reacted at 40 ℃ for 24 hours. After the reaction is finished, the reaction product is naturally cooled to room temperature, hydrogen is carefully discharged, the reaction product is filtered by diatomite, and the organic solvent in the filtrate is removed to obtain 231mg of the product, wherein the yield is 96%.
White solid. 1H NMR (400MHz, T-MeOD) δ 7.06-6.96(m,5H),4.10(s,2H),3.31(T, J ═ 4.0Hz,2H),2.06(T, J ═ 4.0Hz,2H),1.60-1.57(m,2H), 13C NMR (101MHz, T-MeOD) δ 175.74,140.06,129.51,128.54,128.17,62.26,44.09,33.60,29.80.
Example 3
A glass tube with magnetons was charged with 50mg of 2- (2-methylbenzyl) -isoindoline-1, 3-dione (0.2mmol), 2.2mg of potassium tert-butoxide, 2 ml of isopropanol under nitrogen, 10. mu.l of 0.001M catalyst (S/C ═ 20,000), and the flask was transferred to an autoclave, which was then tightened, filled with 1MPa hydrogen and reacted at 100 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 51mg of a white solid with a yield of 99%.
White solid. 1H NMR (400MHz, CDCl3) delta 7.55-7.53(m,1H),7.43-7.41(m,3H),7.38-7.31(m,1H),7.27-7.23(m,3H),7.16-7.10(m,3H),4.60-4.58(m,4H),2.35(s,3H).13C NMR (101MHz, CDCl3) delta 169.97,140.36,138.71,137.83,135.58,131.43,130.96,128.89,128.71,128.60,128.26,127.68,124.94,64.80,44.35,21.51
Example 4
A glass tube with magnetons was charged with 50mg of 2- (3-methylbenzyl) -isoindoline-1, 3-dione (0.2mmol), 0.8mg of sodium hydroxide, 2 ml of isopropanol under nitrogen, 10. mu.l of 0.001M catalyst (S/C ═ 20,000) and then the flask was transferred to an autoclave, the autoclave was screwed down, charged with 10MPa hydrogen and reacted at 20 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 51mg of a white solid with a yield of 99%.
A white solid. 1H NMR (400MHz, CDCl3) δ 7.51-7.49(m,1H),7.41-7.37(m,1H),7.31-7.25(m,3H),7.21-7.17(m,3H),4.60(d, J ═ 12Hz,2H),4.53(s,2H),2.35(s,3H).13C NMR (101MHz, CDCl3) δ 169.79,140.08,136.48,135.54,135.48,131.30,130.82,130.71,128.53,128.19,128.00,127.80,126.39,64.65,42.39,19.12.
Example 5
A glass tube with magnetons was charged with 50mg of 2- (4-methylbenzyl) -isoindoline-1, 3-dione (0.2mmol), 1.2mg of potassium hydroxide, 2 ml of isopropanol under nitrogen, 20. mu.l of 0.001M catalyst (S/C ═ 10,000), and the reaction flask was transferred to an autoclave, which was screwed down, charged with 3MPa hydrogen, and reacted at 40 ℃ for 20 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 51mg of a white solid with a yield of 99%.
White solid. 1H NMR (400MHz, CDCl 3). delta.7.53-7.51 (m,1H),7.45-7.41(m,1H),7.37-7.30(m,2H),7.26-7.23(m,2H),7.17-7.15(m,2H),4.59-4.57(m,4H),2.34(s,3H).13C NMR (101MHz, CDCl 3). delta. 169.95,140.34,137.59,135.62,134.90,131.40,130.94,129.64,128.24,127.94,127.67,64.82,44.13,21.24.
Example 6
A glass tube with magnetons was charged with 52mg of 2- (2-fluorobenzyl) -isoindoline-1, 3-dione (0.2mmol), 2.2mg of sodium tert-butoxide, 2 ml of isopropanol under nitrogen, 20. mu.l of 0.001M catalyst (S/C10,000), and the flask was transferred to an autoclave, which was then tightened, filled with 4MPa hydrogen and reacted at 40 ℃ for 20 hours. After the reaction, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 52mg of a white solid with a yield of 99%.
A white solid. 1H NMR (400MHz, d6-DMSO)) δ 7.54-7.52(m,1H),7.43-7.38(m,2H),7.34-7.27(m,2H),7.14-7.02(m,3H),4.66(d, J ═ 4Hz,1H),4.55(s,1H).13C NMR (101MHz, CDCl3) δ 169.98,162.40,159.95,140.15,135.42,131.42,130.89,130.40,130.36,129.69,129.61,128.27,127.84,125.04,124.89,124.55,124.51,115.72,115.50,64.71,38.39,38.35.
Example 7
A glass tube with magnetons was charged with 48mg of 2-methyl-isoindoline-1, 3-dione (0.3mmol), 3.3mg of potassium tert-butoxide, 3 ml of tetrahydrofuran under nitrogen, 30. mu.l of 0.001M catalyst (S/C10,000) was added, and then the reaction flask was transferred to an autoclave, the autoclave was screwed down, charged with 4MPa hydrogen gas, and reacted at 40 ℃ for 15 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully released, the reaction mixture was filtered through celite, and 49mg of a yellow oily substance was obtained after the organic solvent was removed from the filtrate, with a yield of 99%.
A yellow oily liquid. 1H NMR (400MHz, CDCl3) δ 7.54-7.51(m,1H),7.46-7.34(m,3H),4.61(s,2H),3.03(d, J ═ 4.0Hz,2H), 13C NMR (101MHz, CDCl3) δ 170.70,140.31,135.63,131.26,130.88,128.15,127.45,64.81,26.98.
Example 8
190mg of 2-propyl-isoindoline-1, 3-dione (1.0mmol), 11.2mg of potassium tert-butoxide, 2 ml of tetrahydrofuran under nitrogen protection and 10. mu.l of a 0.001M catalyst (S/C100,000) were added to a glass tube with a magneton, and then the reaction flask was transferred to an autoclave, the autoclave was screwed, charged with 6MPa of hydrogen, and reacted at 60 ℃ for 25 hours. After the reaction, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 190mg of a yellow oily substance in a yield of 99%.
A yellow oily liquid. 1H NMR (400MHz, CDCl3) δ 7.53-7.51(m,1H),7.47-7.43(m,1H),7.417.34(m,2H),4.61(d, J ═ 4.0Hz,2H),4.41(t, J ═ 8.0Hz,1H),3.46-3.41(m,2H),1.69-1.63(m,2H),1.03-0.94(m,3H), 13C NMR (101MHz, CDCl3) δ 167.69,140.40,136.09,131.33,130.98,128.28,127.51,64.94,42.08,22.99,11.57.
Example 9
A glass tube with magnetons was charged with 38mg of 2-isopropyl-isoindoline-1, 3-dione (0.2mmol), 2.0mg of lithium tert-butoxide, 2 ml of tetrahydrofuran under nitrogen, 20. mu.l of 0.001M catalyst (S/C10,000) was added, and then the reaction flask was transferred to an autoclave, the autoclave was screwed down, charged with 4MPa hydrogen, and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully released, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 39mg of a yellow oily substance in a yield of 99%.
Yellow oily liquid. 1H NMR (400MHz, CDCl3) δ 7.53-7.50(m,1H),7.41-7.37(m,1H),7.33-7.29(m,2H),4.51(s,2H),3.24-3.21(m,2H),1.90-1.81(m,1H),2.07-2.00(m,1H),0.95(d, J ═ 8.0Hz,2H), 13C NMR (101MHz, CDCl3) δ 170.17,139.74,134.136.12,131.07,130.74,128.19,127.86,64.62,47.60,28.61,20.24.
Example 10
A glass tube with magnetons was charged with 40mg of 2-tert-butyl-isoindoline-1, 3-dione (0.2mmol), 2.2mg of potassium tert-butoxide, 2 ml of tetrahydrofuran under nitrogen protection, 4. mu.l of 0.001M catalyst (S/C50,000) was added, and then the reaction flask was transferred to an autoclave, the autoclave was screwed down, charged with 4MPa hydrogen, and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully released, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 41mg of a yellow oily substance in a yield of 99%.
A yellow oily liquid. 1H NMR (400MHz, CDCl3) delta 7.48-7.46(m,1H),7.38-7.36(m,1H),7.32-7.28(m,2H),4.51(s,2H),1.45(s,3H).13C NMR (101MHz, CDCl3) delta 169.80,139.41,137.26,130.72,130.60,128.07,127.65,64.46,52.10,28.75.
Example 11
A white solid. A glass tube with magnetons was charged with 44mg of 2-phenyl-isoindoline-1, 3-dione (0.2mmol), 1.0mg of sodium hydroxide, 2 ml of isopropanol under nitrogen, 4. mu.l of 0.001M catalyst (S/C ═ 50,000), and then the flask was transferred to an autoclave, which was then tightened, filled with 4MPa hydrogen and reacted at 40 ℃ for 12 hours. After the reaction, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 45mg of a white solid with a yield of 99%.
A white solid. 99% yield.1H NMR (400MHz, d6-DMSO) δ 7.74-7.72(m,2H),7.60-7.58(m,1H),7.54-7.48(m,2H),7.39-7.32(m,3H),7.11-7.07(m,1H),5.32(s,1H),4.67(d, J ═ 8.0Hz,2H), 13C NMR (101MHz, d6-DMSO) δ 168.90,138.67,135.26,135.14,134.56,131.67,131.04,129.76,127.92,127.28,121.53,65.88.
Example 12
A glass tube with magnetons was charged with 47mg of 2- (4-methylphenyl) -isoindoline-1, 3-dione (0.2mmol), 1.2mg of potassium hydroxide, 2 ml of isopropanol under nitrogen, 10. mu.l of 0.001M catalyst (S/C ═ 20,000), and the flask was transferred to an autoclave, which was then tightly closed, charged with 4MPa of hydrogen, and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully released, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 48mg of a yellow oily substance in a yield of 99%.
A white solid. 1H NMR (400MHz, CDCl 3). delta.7.72-7.70 (m,1H),7.53-7.51(m,2H),7.48-7.47(m,1H),7.43-7.40(m,2H),7.19-7.17(m,2H),4.67(s,2H),2.35(s,3H).13C NMR (101MHz, CDCl 3). delta. 167.90,139.68,136.29,135.34,134.76,131.63,131.17,129.77,128.62,128.25,120.53,64.80,21.08.
Example 13
A glass tube with magnetons was charged with 51mg of 2- (4-methylphenyl) -isoindoline-1, 3-dione (0.2mmol), 2.8mg of potassium carbonate, 2 ml of tetrahydrofuran under nitrogen, 20. mu.l of 0.001M catalyst (S/C. 10,000) was added, and then the reaction flask was transferred to an autoclave, the autoclave was screwed, charged with 4MPa of hydrogen, and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 51mg of a white solid with a yield of 99%.
A white solid. 1H NMR (400MHz, CDCl3) δ 7.73-7.70(m,1H),7.56-7.53(m,2H),7.49-7.47(m,1H),7.44-7.41(m,2H),6.92(d, J ═ 8.0Hz,2H),4.68(d, J ═ 8.0Hz,2H),3.82(s,3H), 13C NMR (101MHz, CDCl3) δ 167.83,157.00,139.79,136.26,131.62,131.18,130.99,128.62,128.20,122.31,114.45,64.86,55.68.
Example 14
A glass tube with magnetons was charged with 51mg of 2- [2- (5-chloropyridine) ] -isoindoline-1, 3-dione (0.2mmol), 2.2mg of sodium carbonate, 2 ml of isopropanol under nitrogen, 100. mu.l of 0.001M catalyst (S/C2,000) was added, and then the reaction flask was transferred to an autoclave, which was screwed down, charged with 4MPa of hydrogen, and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 51mg of a white solid with a yield of 99%.
White solid. 1H NMR (400MHz, CDCl3) δ 8.00(d, J ═ 4.0Hz,2H),7.94-7.91(m,1H),7.71-7.67(m,1H),7.52-7.50(m,1H),7.52-7.48(m,1H),7.39-7.36(m,2H),6.46(d, J ═ 8.0Hz,2H),5.33(s,2H), 13C NMR (101MHz, CDCl3) δ 174.25,156.83,146.65,146.23,137.82,134.16,129.19,125.93,125.86,122.22,121.06,109.70,69.80.
Example 15
43mg of 1,3, 5-tribenzyltretrahydropyrolo [3,4-d ] imidazole-2,4,6(5H) -trione (0.1mmol), 6.7mg of cesium carbonate, 1 ml of isopropanol under nitrogen protection, 50. mu.l of 0.001M catalyst (S/C2,000) were added to a glass tube with a magnet, and then the reaction flask was transferred to an autoclave, the autoclave was screwed, charged with 4MPa of hydrogen gas, and reacted at 40 ℃ for 24 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 43mg of a white solid with a yield of 99%.
White solid, > 99% yield.1H NMR (400MHz, T-MeOD) δ 7.36-7.30(m,7H),7.22-7.15(m,7H),4.90(d, J ═ 8.0Hz,1H),4.81(d, J ═ 8.0Hz,1H),4.53(d, J ═ 8.0Hz,1H),4.46-4.35(m,2H),4.15(d, J ═ 8.0Hz,1H),4.05(d, J ═ 8.0Hz,1H),3.82(d, J ═ 4.0Hz,1H), 13C NMR (101MHz, T-MeOD) δ 172.14,160.70,137.96,137.86,137.05,129.86,129.84,129.80,129.75,129.70,129.35,129.31,129.03,129.01,128.82,128.77,84.99,62.04,55.99,48.27,46.69,43.93.
Example 16
40mg of 1-phenylpiperidine-2, 6-dione (0.2mmol), 2.2mg of potassium tert-butoxide, 2 ml of isopropanol under nitrogen protection and 10. mu.l of 0.001M catalyst (S/C20,000) were added to a glass tube with a magneton, and then the reaction flask was transferred to an autoclave, the autoclave was screwed, charged with 4MPa of hydrogen gas, and reacted at 40 ℃ for 12 hours. After the reaction, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 40mg of a white solid with a yield of 99%.
A white solid. 99% yield.1H NMR (400MHz, T-MeOD) δ 7.32-7.22(m,5H),4.36(s,2H),3.56(T, J ═ 4.0Hz,2H),2.26(T, J ═ 4.0Hz,2H),1.71-1.68(m,2H),1.57-1.54(m,2H), 13C NMR (101MHz, T-MeOD) δ 175.93,140.08,129.52,128.56,128.18,62.49,44.07,36.76,33.08,23.44.
Example 17
A glass tube with magnetons was charged with 38mg of 1-benzylpyrroline-2, 5-dione (0.2mmol), 2.2mg of sodium tert-butoxide, 2 ml of isopropanol under nitrogen protection, 5. mu.l of 0.001M catalyst (S/C40,000) was added, and then the reaction flask was transferred to an autoclave, the autoclave was tightened, charged with 4MPa hydrogen and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully released, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 38mg of a yellow oily substance in a yield of 99%.
A yellow oily liquid. 99% yield.1H NMR (400MHz, T-MeOD) δ 7.06-6.96(m,5H),4.10(s,2H),3.31(T, J ═ 4.0Hz,2H),2.06(T, J ═ 4.0Hz,2H),1.60-1.57(m,2H).13C NMR (101MHz, T-MeOD) δ 175.74,140.06,129.51,128.54,128.17,62.26,44.09,33.60,29.80.
Example 18
A glass tube with magnetons was charged with 48mg of 2- (4-fluorobenzene) isoindoline-1, 3-dione (0.2mmol), 6.7mg of cesium carbonate, 2 ml of isopropanol under nitrogen protection, 5. mu.l of 0.001M catalyst (S/C40,000) was added thereto, and the mixture was reacted at 40 ℃ for 12 hours under 4MPa hydrogen. After the reaction is finished, the reaction product is naturally cooled to room temperature, hydrogen is carefully discharged, the reaction product is filtered by diatomite, and 47mg of the product is obtained after the organic solvent is removed from the filtrate, and the yield is 99%.
A white solid. 1 H NMR(400MHz,CDCl 3 )δ7.75-7.72(m,1H),7.63-7.60(m,2H),7.50-7.47(m,1H),7.45-7.39(m,2H),7.09-7.05(m,2H),4.69(d,J＝4.0Hz,2H),3.87(t,J＝4.0Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ167.77,161.01,158.59,139.29,136.09,134.05,134.02,131.77,131.19,128.77,128.58,122.28,122.20,116.06,115.83,64.81.HRMS(ESI)calcd.for C 14 H 12 FNO 2 [M+H]+:246.0852,Found:246.0924.
Example 19
A glass tube with magnetons was charged with 48mg of 2- (3-fluorobenzene) isoindoline-1, 3-dione (0.2mmol) and 2.2mg of potassium tert-butoxide, 2 ml of isopropanol was added under nitrogen protection, 5. mu.l of 0.001M catalyst (S/C40,000) was added, hydrogen gas at 4MPa was introduced, and the reaction was carried out at 40 ℃ for 12 hours. After the reaction is finished, the reaction product is naturally cooled to room temperature, hydrogen is carefully discharged, the reaction product is filtered by diatomite, and 47mg of the product is obtained after the organic solvent is removed from the filtrate, and the yield is 99%.
A white solid. 1 H NMR(400MHz,T-MeOD)δ7.68-7.63(m,2H),7.57-7.52(m,2H),7.44-7.33(m,3H),6.90-6.85(m,1H),4.77(s,2H). 13 C NMR(101MHz,T-MeOD)δ170.38,165.53,163.11,141.75,141.64,140.67,136.72,131.91,131.27,131.17,130.07,129.15,128.75,116.96,116.93,111.93,111.71,108.65,108.38,66.67,63.46.HRMS(ESI)calcd.for C 14 H 12 FNO 2 [M+H]+:246.0852,Found:246.0925.
Example 20
A glass tube with magnetons was charged with 60mg of 2- (4-bromobenzene) isoindoline-1, 3-dione (0.2mmol), 2.1mg of sodium hydroxide, 2 ml of isopropanol under nitrogen protection, 5. mu.l of 0.001M catalyst (S/C. RTM. 40,000) was added, and then the reaction flask was transferred to an autoclave, the autoclave was screwed, charged with 4MPa hydrogen, and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 59mg of a white solid with a yield of 98%.
A white solid. 1 H NMR(600MHz,T-MeOD)δ7.65-7.63(m,3H),7.56-7.55(m,1H),7.52-7.48(m,3H),7.43-7.41(m,1H),4.76(s,2H). 13 C NMR(150MHz,T-MeOD)δ170.14,140.53,139.08,136.59,132.71,131.75,129.93,128.99,128.60,123.15,117.76,63.33.
Example 21
A glass tube with a magneton was charged with 46mg of (1R,5S) -3-benzyl-6, 6-dimethyl-3-azabicyclo [3.1.0] hexane-2, 4-dione (0.2mmol), 2.2mg of lithium tert-butoxide, 2 ml of isopropanol under nitrogen protection, 5. mu.l of 0.001M catalyst (S/C40,000) was added, and then the reaction flask was transferred to an autoclave, which was then tightened, charged with 4MPa hydrogen and reacted at 40 ℃ for 12 hours. After the reaction, the reaction mixture was naturally cooled to room temperature, hydrogen was carefully removed, the reaction mixture was filtered through celite, and the organic solvent was removed from the filtrate to obtain 45mg of a white solid with a yield of 98%.
A white solid. 1 H NMR(600MHz,T-MeOD)δ7.32-7.26(m,4H),7.24-7.22(m,1H),4.37-4.31(m,2H),4.00-3.96(m,1H),3.88-3.84(m,1H),1.53(d,J＝4.0Hz,1H),1.30-1.24(m,1H),1.24(s,3H),1.19(s,3H). 13 C NMR(150MHz,T-MeOD)δ173.39,140.32,129.48,128.50,128.10,59.03,44.08,34.07,31.86,29.12,24.68,14.92.
Example 22
To a glass tube with a magneton were added 50mg of (3aR,4S,7R,7aS) -2-phenyl-3 a,4,7,7 a-tetrahydro-1H-4, 7-methanoisoindole-1, 3(2H) -dione (0.2mmol), 6.8mg of sodium carbonate, 2 ml of tetrahydrofuran under nitrogen protection, 5. mu.l of 0.001M catalyst (S/C ═ 40,000), and then the reaction flask was transferred to an autoclave, which was then tightened, charged with 4MPa hydrogen, and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen gas was carefully released, the reaction mixture was filtered through celite, and 49mg of a yellow oily substance was obtained after the organic solvent was removed from the filtrate, with a yield of 98%.
A white solid. 1 H NMR(600MHz,T-MeOD)δ7.32-7.25(m,5H),4.59(s,2H),2.68(s,2H),2.58(s,2H),1.65(d,J＝4.0Hz,2H),1.38-1.36(m,2H),1.15(d,J＝8.0Hz,1H),0.94(d,J＝8.0Hz,1H). 13 C NMR(150MHz,T-MeOD)δ180.72,137.69,129.58,129.52,128.85,49.86,43.15,41.13,33.72,30.67,28.89.HRMS(ESI)calcd.for C 16 H 21 NO 2 [M+H]+:260.1572,Found:260.1654.
Example 23
To a glass tube with a magneton were added 50mg of (3aR,4R,7S,7aS) -2-phenyl-3 a,4,7,7 a-tetrahydro-1H-4, 7-methanoisoindole-1, 3(2H) -dione (0.2mmol), 6.8mg of cesium carbonate, 2 ml of tetrahydrofuran under nitrogen protection, 5. mu.l of 0.001M catalyst (S/C ═ 40,000), and then the reaction flask was transferred to an autoclave, which was then tightened, charged with 4MPa hydrogen, and reacted at 40 ℃ for 12 hours. After the reaction was completed, the reaction mixture was naturally cooled to room temperature, hydrogen gas was carefully released, the reaction mixture was filtered through celite, and 49mg of a yellow oily substance was obtained after the organic solvent was removed from the filtrate, with a yield of 98%.
A white solid. 1 H NMR(600MHz,T-MeOD)δ7.39-7.38(m,2H),7.31-7.25(m,3H),3.31-3.29(m,2H),3.14-3.11(m,2H),2.64(s,2H),2.16(s,1H),1.67-1.66(m,1H),1.57-1.55(m,1H),1.40(d,J＝8.0Hz,2H),0.96-0.95(m,2H). 13 C NMR(150MHz,CDCl 3 )δ180.34,137.83,129.89,129.52,128.94,49.88,42.97,42.95,40.55,25.29.HRMS(ESI)calcd.for C 16 H 21 NO 2 [M+H]+:260.1572,Found:260.1654。
Claims (9)
1. A method for preparing a hydroxyamide represented by formula (I),
wherein R is 1 ，R 2 ，R 3 Independently of each other is H, C1-C12 alkyl, aryl, R 1 ，R 2 Or C1-C12 alkyl, aryl connected by a ring;
the catalyst of the homogeneous catalytic hydrogenation reaction is obtained by in-situ complexing of a ligand and an iridium metal precursor, the structure of the ligand is a ferrocene ligand with a structure (III),
2. The preparation method of claim 1, wherein the solvent used in the homogeneous catalytic hydrogenation reaction is one of isopropanol and tetrahydrofuran or a mixture of isopropanol and tetrahydrofuran in any proportion.
3. The preparation method of claim 1, wherein the homogeneous catalytic hydrogenation reaction further comprises a base, wherein the base is one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium hydroxide, sodium carbonate, potassium carbonate and cesium carbonate or a mixture of the two in any proportion.
4. The preparation process according to claim 1, wherein the ratio of the catalyst to the cyclic imide is 1:10,000-50,000.
5. The production method according to claim 2, wherein the solvent is isopropyl alcohol.
6. The method according to claim 3, wherein the base is potassium tert-butoxide and the ratio of the base to the cyclic imide is 1: 10-50.
7. The production method according to claim 1, wherein the temperature of the homogeneous catalytic hydrogenation reaction is 40 to 60 degrees celsius.
8. The production process according to claim 1, wherein the hydrogen pressure in the homogeneous catalytic hydrogenation is 4 to 6 MPa.
9. The production process according to claim 1, wherein the time for the homogeneous catalytic hydrogenation reaction is 20 to 25 hours.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4082748A (en) * | 1976-08-27 | 1978-04-04 | The Dow Chemical Company | Process for production of oxazine diones |
| CN107417562A (en) * | 2017-08-14 | 2017-12-01 | 凯特立斯（深圳）科技有限公司 | It is catalyzed the method for prochirality alpha ketoamide synthesis of chiral α hydroxy amides |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4082748A (en) * | 1976-08-27 | 1978-04-04 | The Dow Chemical Company | Process for production of oxazine diones |
| US4130711A (en) * | 1976-08-27 | 1978-12-19 | The Dow Chemical Company | Process for production of piperazinediones |
| CN107417562A (en) * | 2017-08-14 | 2017-12-01 | 凯特立斯（深圳）科技有限公司 | It is catalyzed the method for prochirality alpha ketoamide synthesis of chiral α hydroxy amides |
Non-Patent Citations (4)
| Title |
|---|
| "Chemoselective Hydrogenation of Imides Catalyzed by Cp*Ru(PN) Complexes and Its Application to the Asymmetric Synthesis of Paroxetine";Masato Ito等;《J. AM. CHEM. SOC.》;20061219;第129卷(第2期);第290-291页 * |
| "Desymmetrization of meso-Cyclic Imides via Enantioselective Monohydrogenation";Satoshi Takebayashi等;《J. AM. CHEM. SOC.》;20100824;第132卷;第12832-12834页 * |
| "Highly chemoselective hydrogenation of cyclic imides to ω -hydroxylactams or ω -hydroxyamides catalyzed by iridium catalysts";Chao Wu等;《Org. Chem. Front. ,》;20210930;第8卷;第6530-6534页 * |
| "Highly Enantioselective Hydrogenative Desymmetrization of Bicyclic Imides Leading to Multiply Functionalized Chiral Cyclic Compounds";Masato Ito等;《J. AM. CHEM. SOC.》;20100730;第132卷;第11414-11415页 * |
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