CN110746342A - 一种羟基内酰胺的制备方法 - Google Patents
一种羟基内酰胺的制备方法 Download PDFInfo
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- -1 hydroxy lactam Chemical class 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 16
- 125000003118 aryl group Chemical group 0.000 claims abstract description 12
- 238000009905 homogeneous catalytic hydrogenation reaction Methods 0.000 claims abstract description 11
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 3
- 238000006467 substitution reaction Methods 0.000 claims abstract description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 43
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 239000003446 ligand Substances 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 6
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 229910052741 iridium Inorganic materials 0.000 claims description 5
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 5
- 239000002243 precursor Substances 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 4
- 230000000536 complexating effect Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 34
- 125000004429 atom Chemical group 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
- 239000007795 chemical reaction product Substances 0.000 description 42
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 239000000706 filtrate Substances 0.000 description 22
- 239000011521 glass Substances 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 22
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- 239000007787 solid Substances 0.000 description 22
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 239000012018 catalyst precursor Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
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- GBBSUAFBMRNDJC-MRXNPFEDSA-N (5R)-zopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-MRXNPFEDSA-N 0.000 description 1
- ZTUKZULGOCFJET-UHFFFAOYSA-N 1-phenylpyrrolidine-2,5-dione Chemical compound O=C1CCC(=O)N1C1=CC=CC=C1 ZTUKZULGOCFJET-UHFFFAOYSA-N 0.000 description 1
- DLGAPXQHTIJNJA-UHFFFAOYSA-N 2-(2-methylpropyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CC(C)C)C(=O)C2=C1 DLGAPXQHTIJNJA-UHFFFAOYSA-N 0.000 description 1
- ZKHXRXJMCPSISR-UHFFFAOYSA-N 2-[(2-fluorophenyl)methyl]isoindole-1,3-dione Chemical compound FC1=CC=CC=C1CN1C(=O)C2=CC=CC=C2C1=O ZKHXRXJMCPSISR-UHFFFAOYSA-N 0.000 description 1
- BZTGCJMEAYVNSF-UHFFFAOYSA-N 2-[(2-methylphenyl)methyl]isoindole-1,3-dione Chemical compound CC1=CC=CC=C1CN1C(=O)C2=CC=CC=C2C1=O BZTGCJMEAYVNSF-UHFFFAOYSA-N 0.000 description 1
- GGYRSKHFTUAHBW-UHFFFAOYSA-N 2-[(3-methylphenyl)methyl]isoindole-1,3-dione Chemical compound CC1=CC=CC(CN2C(C3=CC=CC=C3C2=O)=O)=C1 GGYRSKHFTUAHBW-UHFFFAOYSA-N 0.000 description 1
- KGYUBBFNBRAXAV-UHFFFAOYSA-N 2-[(4-methylphenyl)methyl]isoindole-1,3-dione Chemical compound C1=CC(C)=CC=C1CN1C(=O)C2=CC=CC=C2C1=O KGYUBBFNBRAXAV-UHFFFAOYSA-N 0.000 description 1
- UDMQMFVAVBUAOT-UHFFFAOYSA-N 2-benzyl-4-chloroisoindole-1,3-dione Chemical compound C(C1=CC=CC=C1)N1C(C=2C(C1=O)=C(C=CC=2)Cl)=O UDMQMFVAVBUAOT-UHFFFAOYSA-N 0.000 description 1
- GNUKPTBHTMHTRJ-UHFFFAOYSA-N 2-benzyl-5-chloroisoindole-1,3-dione Chemical compound C(C1=CC=CC=C1)N1C(C2=CC=C(C=C2C1=O)Cl)=O GNUKPTBHTMHTRJ-UHFFFAOYSA-N 0.000 description 1
- ZXLYYQUMYFHCLQ-UHFFFAOYSA-N 2-methylisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(C)C(=O)C2=C1 ZXLYYQUMYFHCLQ-UHFFFAOYSA-N 0.000 description 1
- MFUPLJQNEXUUDW-UHFFFAOYSA-N 2-phenylisoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1=CC=CC=C1 MFUPLJQNEXUUDW-UHFFFAOYSA-N 0.000 description 1
- RLARUBPTQYKZKA-UHFFFAOYSA-N 2-propylisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC)C(=O)C2=C1 RLARUBPTQYKZKA-UHFFFAOYSA-N 0.000 description 1
- AMEZJARRAUZZHY-UHFFFAOYSA-N 2-tert-butylisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(C(C)(C)C)C(=O)C2=C1 AMEZJARRAUZZHY-UHFFFAOYSA-N 0.000 description 1
- WITXFYCLPDFRNM-UHFFFAOYSA-N N-Benzylphthalimide Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 WITXFYCLPDFRNM-UHFFFAOYSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229960000820 zopiclone Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/62—Naphtho [c] pyrroles; Hydrogenated naphtho [c] pyrroles
- C07D209/66—Naphtho [c] pyrroles; Hydrogenated naphtho [c] pyrroles with oxygen atoms in positions 1 and 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/827—Iridium
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
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- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Abstract
Description
技术领域
本发明涉及一种羟基内酰胺化合物的制备方法。
背景技术
羟基内酰胺是一种重要的有机化合物。一方面它作为酰亚胺阳离子前体,可以发生多种有机反应,生成具有重要作用的精细有机化工品。另一方面,该结构广泛存在于天然产物以及生物活性分子中,是一种优势的医药、农药等先导化合物的结构。甚至于该类结构已经是目前市场上一线用药的母核结构,例如目前应用广泛的安眠类药物佐匹克隆。
为了得到这类化合物,目前已经发展了一些方法,归纳起来主要有三类:一是通过金属或者金属氢化物还原环状酰亚胺化合物,代表性的试剂有锌,硼氢化钠等(Journal ofOrganic Chemistry,82(4),2193-2198;2017;Synthetic Communications,36(4),435-444;2006)。该类方法需要用到当量的还原试剂,反应对水敏感,后处理产生大量的三废,没有大规模应用潜力。二是通过硅烷、硼烷等非金属还原试剂还原(SyntheticCommunications,28(13),2507-2516; 1998)。该类方法也需要当量以上的还原剂,对水敏感,反应过程中产生的酸性气体对设备有较大腐蚀,后处理过程中三废量大,也不适宜工业化生产。三是通过催化氢化的方法。该类方法原子经济性高,副产物少,后处理简单,几乎无三废,是一种理想的方法。但目前该类方法的缺点是活性低,选择性差。例如非均相的钯炭催化剂,用量超过10%(WO 2007088189, WO 2009019281,WO 2008061955)。对于均相催化剂,S.H.Bergens等人(Journal of the American Chemical Society,132(37),12832-12834;2010)利用Noyori类型钌催化剂,成功实现了羟基内酰胺的制备,最低催化剂用量为0.02%。虽然该过程较为绿色,但催化剂用量大,成本高,达不到工业应用的要求。
发明内容
一方面公开一种环状酰亚胺均相催化氢化直接制备羟基内酰胺化合物的方法,通过本方法的实施,可以高效制备羟基内酰胺化合物,完全避免使用危险性试剂硼氢化钠等。
本发明通过以下技术方案实现:
一种羟基内酰胺化式(I)的制备方法,由式(II)所示环状酰亚胺在溶剂中,在碱存在下通过均相催化氢化反应制得
其中,R1,R2,R3,分别独立为H,C1-C12的烷基,芳基或者含杂原子取代的烷基,芳基,R1,R2也可以是通过环连接起来的C1-C12的烷基,芳基或者含杂原子取代的烷基,芳基。
在一些实施例中,所述催化剂为配体和铱金属前体的原位配合物,其中配体的结构为具有(III)或(IV)结构的二茂铁配体,其中Ar为苯基,4-甲基苯基,3,5-二甲基苯基,3,5- 二甲基-4-甲氧基苯基;铱金属前体为[Ir(COD)Cl]2;溶剂为异丙醇、四氢呋喃、甲苯的一种或者任意比例的混合物,碱为叔丁醇钾、叔丁醇钠、叔丁醇锂、氢氧化钾、氢氧化钠、碳酸钠、碳酸钾、碳酸铯的一种或者任意比例混合物。
在一些实施例中,所述催化剂与环状酰亚胺的比例为1:5,000-100,000,优选1:20, 000-50,000。
在一些实施例中,所述溶剂为异丙醇、四氢呋喃、甲苯中的一种或几种组合,更优选异丙醇。
在一些实施例中,所述碱为叔丁醇钾,碱与环状酰亚胺的比例为1:5-100,优选1:10-50。
在一些实施例中,所述均相催化氢化反应的温度为20-80摄氏度,更优选40-60摄氏度。
在一些实施例中,所述均相催化氢化反应的氢气压力为1-10MPa,优选4-6MPa。
在一些实施例中,所述均相催化氢化反应的时间为10-30小时,优选20-25小时。
本发明采用弱给电子性的三齿配体与铱配合做催化剂,一方面通过三齿配位增强了催化剂的稳定性,不易失活,另一方面精细的调控了催化剂的活性,能够选择性活化一分子氢气对环状酰亚胺进行还原,一步反应专一生成羟基内酰胺化合物。同时与现有技术相比,本方法具有原子经济性高、选择性单一、三废少、易于工业化等特点。本发明的催化剂转化数(TON, turnover number)高达100,000,大幅度领先于目前该领域的所有已知催化剂,易于工业化放大。
具体实施方式
以下通过具体的实施例对本发明上述的内容作进一步的详细说明,但本发明不局限于实施例。
实施例1
在氩气气氛下往4.0mL的瓶中加入催化剂前体[Ir(COD)Cl]2(6.71mg,1.0×10- 2mmol,1 eq),配体(III)(2.4×10-2mmol,2.4eq)和无水异丙醇(iPrOH,2.0mL)。将混合物在在充满氩气的手套箱中25℃下搅拌12.0h,得到橙红色溶液,该催化剂溶液可以直接用来做催化反应。
实施例2
在氩气气氛下往4.0mL的瓶中加入催化剂前体[Ir(COD)Cl]2(6.71mg,1.0×10- 2mmol,1 eq),配体IV(2.4×10-2mmol,2.4eq)和无水异丙醇(iPrOH,2.0mL)。将混合物在在充满氩的手套箱中25℃下搅拌12.0h,得到橙红色溶液,该催化剂溶液可以直接用来做催化反应。
实施例3
在带磁子的玻璃试管中加入237mg 2-苄基异吲哚啉-1,3-二酮(1mmol),11.2mg叔丁醇钾,氮气保护下加入2毫升异丙醇,加入10微升0.01M的催化剂(S/C=10,000),充入4MPa 氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品232mg,收率97%。
白色固体,1H NMR(400MHz,d6-DMSO)δ7.71-7.69(m,1H),7.66-7.53(m,3H),7.53-7.29 (m,4H),7.28-7.23(m,1H),5.67(d,J=8.0Hz,1H),4.92(d,J=16Hz,1H),4.37(d,J=12Hz, 1H).13C NMR(101MHz,CDCl3)δ166.15,144.89,137.74,132.09,131.42,129.42,128.49, 127.68,127.11,123.76,122.47,80.28,42.11.
实施例4
在带磁子的玻璃试管中加入257mg 2-苄基-4-氯异吲哚啉-1,3-二酮(1mmol),11.2mg叔丁醇钠,氮气保护下加入2毫升四氢呋喃,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,80℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品251mg,两种异构体比例为2.5:1,收率97%。
白色固体。1H NMR(400MHz,d6-DMSO)δ7.69-7.53(m,3H),7.36-7.26(m,5H),7.53-7.29 (m,4H),7.28-7.23(m,1H),6.92(d,J=8.0Hz,0.3H),6.82(d,J=8.0Hz,0.7H),5.72(d,J=8.0 Hz,0.3H),5.66(d,J=8.0Hz,0.7H),4.93-4.85(m,1H),4.38-4.34(m,1H).13CNMR(101MHz, d6-DMSO)δ165.01,163.85,147.71,141.33,137.51,137.37,133.62,132.66,131.71,130.78, 129.44,129.08,128.60,128.56,127.78,127.27,127.22,127.10,122.88,121.56,79.64,79.31, 40.15.HRMS(ESI)calcd.for C15H12ClNO2[M+H]+:274.0557,Found:274.0628.
实施例5
在带磁子的玻璃试管中加入257mg 2-苄基-5-氯异吲哚啉-1,3-二酮(1mmol),6mg氢氧化钾,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入6MPa氢气,20℃反应30小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品246mg,两种异构体比例为1:1,收率95%。
白色固体。1H NMR(400MHz,CDCl3)δ7.54-7.39(m,3H),7.31-7.27(m,5H),5.56(d,J= 8.0Hz,1H),4.94-4.89(m,1H),4.29-4.25(m,1H),4.00-3.91(m,1H).13C NMR(101MHz,CDCl3)δ166.51,166.22,145.65,142.20,139.00,136.51,136.45,136.29,133.05,132.64,130.37, 129.73,128.98,128.61,128.57,127.99,127.97,124.88,124.60,124.20,123.60,80.81,80.65, 42.96.HRMS(ESI)calcd.for C15H12ClNO2[M+H]+:274.0557,Found:274.0629.
实施例6
在带磁子的玻璃试管中加入224mg 2-苯基异吲哚啉-1,3-二酮(1mmol),6mg氢氧化钠,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入10MPa氢气,30℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品220mg,收率97%。
白色固体。1H NMR(400MHz,d6-DMSO)δ7.78-7.67(m,5H),7.63-7.60(m,1H),7.46-7.42 (m,2H),7.23-7.19(m,1H),6.54(s,1H).13C NMR(101MHz,CDCl3)δ165.43,144.40,137.46, 132.75,131.28,129.67,128.66,124.64,123.66,122.83,122.30,81.87.
实施例7
在带磁子的玻璃试管中加入237mg 2-(对甲基苯)异吲哚啉-1,3-二酮(1mmol),6mg 氢氧化锂,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品230mg,收率96%。
白色固体。1H NMR(400MHz,d6-DMSO)δ7.78-7.67(m,5H),7.63-7.60(m,1H),7.46-7.42 (m,2H),7.23-7.19(m,1H),6.54(s,1H).13C NMR(101MHz,CDCl3)δ168.44,145.66,136.97, 135.54,133.99,132.70,130.92,130.48,125.08,124.63,124.15,84.37,21.04.
实施例8
在带磁子的玻璃试管中加入253mg 2-(4-甲氧基苯)异吲哚啉-1,3-二酮(1mmol),10mg 叔丁醇锂,氮气保护下加入2毫升异丙醇,加入20微升0.01M的催化剂(S/C=5,000),充入1MPa氢气,60℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品250mg,收率98%。
白色固体;95%收率.1H NMR(600MHz,T-MeOD)δ7.81-7.79(m,1H),7.71-7.67(m,2H), 7.61-7.58(m,1H),7.54-7.52(m,2H),7.02-7.00(m,2H),6.31(s,1H),3.83(s,3H).13CNMR(150 MHz,T-MeOD)δ168.61,159.61,145.77,133.94,132.72,130.92,130.79,127.32,124.65,124.14, 115.26,84.82,55.93.
实施例9
在带磁子的玻璃试管中加入241mg 2-(2-氟苯)异吲哚啉-1,3-二酮(1mmol),11mg叔丁醇钾,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品237mg,收率97%。
白色固体。1H NMR(400MHz,T-MeOD)δ7.82-7.80(m,1H),7.72-7.65(m,3H),7.62-7.58 (m,2H),7.46-7.40(m,1H),6.99-6.94(m,1H),6.45(s,1H).13C NMR(101MHz,CDCl3)δ168.36,165.46,163.04,145.45,140.34,140.24,135.44,134.36,132.37,131.25,131.16,131.06, 130.09,126.20,124.66,124.34,123.65,119.15,119.12,112.89,112.68,110.86,110.60,84.02, 71.42.
实施例10
在带磁子的玻璃试管中加入258mg 2-(5-氯吡啶)异吲哚啉-1,3-二酮(1mmol),11mg 碳酸钾,氮气保护下加入2毫升四氢呋喃,加入2微升0.01M的催化剂(S/C=50,000),充入6MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品251mg,收率96%。
白色固体。1H NMR(400MHz,CDCl3)δ8.59(d,J=8.0Hz,1H),8.34(d,J=4.0Hz,1H),7.91-7.89(m,1H),7.79-7.76(m,1H),7.72-7.67(m,2H),7.60-7.56(m,1H),6.73(d,J=4.0Hz, 1H),5.52(d,J=4.0Hz,1H).13C NMR(101MHz,CDCl3)δ166.48,150.39,146.06,142.20, 138.77,133.68,131.73,130.33,126.99,124.30,123.81,115.12,82.30.
实施例11
在带磁子的玻璃试管中加入251mg 2-(2-甲基苄基)异吲哚啉-1,3-二酮(1mmol),15mg 叔丁醇钠,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品249mg,收率98%。
白色固体。1H NMR(400MHz,T-MeOD)δ7.79-7.76(m,1H),7.66-7.54(m,3H),7.23-7.08 (m,4H),5.66(s,1H),5.06(d,J=16Hz,1H),4.38(d,J=12Hz,1H),2.31(d,J=4Hz,3H).13C NMR(101MHz,T-MeOD)δ169.26,146.13,139.59,138.39,133.66,132.61,130.78,129.73, 129.66,129.25,126.17,124.68,123.94,82.07,43.61,21.42.HRMS(ESI)calcd.for C16H15NO2 [M+H]+:254.1103,Found:254.1175.
实施例12
在带磁子的玻璃试管中加入251mg 2-(3-甲基苄基)异吲哚啉-1,3-二酮(1mmol),10mg 甲醇钠,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品248mg,收率98%。
白色固体。1H NMR(400MHz,CDCl3)δ7.62-7.60(m,1H),7.56-7.54(m,2H),7.46-7.43(m, 1H),7.16-7.13(m,4H),5.50(s,1H),4.68(d,J=16Hz,1H),4.21(d,J=16Hz,1H),2.31(s,3H). 13C NMR(101MHz,CDCl3)δ167.47,144.25,136.63,134.46,132.48,131.16,130.64,129.75, 128.85,127.84,126.30,123.62,123.44,81.14,40.32,19.34.HRMS(ESI)calcd.for C16H15NO2 [M+H]+:254.1103,Found:254.1174.
实施例13
在带磁子的玻璃试管中加入251mg 2-(4-甲基苄基)异吲哚啉-1,3-二酮(1mmol),12mg 甲醇钾,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入 4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品249mg,收率98%。
白色固体。1H NMR(400MHz,CDCl3)δ7.64-7.63(m,1H),7.55-7.54(m,2H),7.46-7.43(m, 1H),7.20-7.18(m,2H),7.10-7.08(m,2H),5.57(s,1H),4.80(d,J=16Hz,1H),4.19(d,J=12Hz, 1H),2.30(s,3H).13C NMR(101MHz,CDCl3)δ167.43,144.09,137.49,133.87,132.43,131.47, 129.86,129.52,128.60,123.53,123.49,81.07,42.49,21.22.
实施例14
在带磁子的玻璃试管中加入161mg 2-甲基异吲哚啉-1,3-二酮(1mmol),6mg氢氧化钠,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气, 40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品158mg,收率97%。
白色固体。1H NMR(400MHz,CDCl3)δ7.60-7.58(m,1H),7.56-7.52(m,2H),7.42-7.38(m, 1H),5.29(s,1H),2.91(s,3H).13C NMR(101MHz,CDCl3)δ167.70,143.92,132.27,131.55, 129.83,123.35,123.19,83.71,26.23.
实施例15
在带磁子的玻璃试管中加入189mg 2-正丙基异吲哚啉-1,3-二酮(1mmol),20mg碳酸铯,氮气保护下加入2毫升四氢呋喃,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品184mg,收率96%。
白色固体。1H NMR(400MHz,CDCl3)δ7.54-7.47(m,2H),7.43-7.41(m,1H),7.36-7.32(m, 1H),5.67(d,J=8.0Hz,1H),3.34-3.27(m,1H),3.17-3.10(m,1H),1.59-1.49(m,2H),0.83(t,J= 8.0Hz,3H).13C NMR(101MHz,CDCl3)δ170.26,144.11,132.08,131.44,129.53,123.31,13.04, 81.61,40.67,21.48,11.43.
实施例16
在带磁子的玻璃试管中加入203mg 2-异丁基异吲哚啉-1,3-二酮(1mmol),10mg叔丁醇锂,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品198mg,收率97%。
白色固体。1H NMR(400MHz,CDCl3)δ7.62-7.54(m,3H),7.46-7.42(m,1H),5.74(s,1H), 3.30-3.24(m,1H),3.15-3.10(m,1H),2.07-2.00(m,1H),0.95(d,J=4.0Hz,3H),0.84(d,J=4.0 Hz,3H).13C NMR(101MHz,CDCl3)δ168.17,134.45,131.49,123.07,44.77,27.44.
实施例17
在带磁子的玻璃试管中加入203mg 2-叔丁基异吲哚啉-1,3-二酮(1mmol),23mg甲醇钾,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品199mg,收率98%。
白色固体。1H NMR(400MHz,CDCl3)δ7.77-7.68(m,1H),7.53-7.44(m,3H),6.00(d,J= 4.0Hz,1H),1.61(s,3H).13C NMR(101MHz,CDCl3)δ168.06,143.62,132.82,132.14,129.66, 123.16,122.83,82.41,54.89,28.72.
实施例18
在带磁子的玻璃试管中加入257mg 2-(2-氟苄基)异吲哚啉-1,3-二酮(1mmol),9mg 碳酸锂,氮气保护下加入2毫升甲苯,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品253mg,收率98%。
白色固体。1H NMR(400MHz,d6-DMSO))δ7.63-7.55(m,1H),7.47-7.43(m,1H),7.53-7.29 (m,4H),7.26-7.21(m,2H),7.06-6.99(m,2H),5.64(s,1H),4.62(d,J=16Hz,1H),4.42(d,J=16 Hz,1H).13C NMR(101MHz,CDCl3)δ167.70,162.16,159.71,144.15,132.57,131.10,130.76, 130.73,129.84,129.61,129.53,124.49,124.45,123.86,123.71,123.64,123.47,115.68,115.46, 81.46,81.45,36.38,36.34.HRMS(ESI)calcd.forC15H12FNO2[M+H]+:258.0852,Found: 258.0924.
实施例19
在带磁子的玻璃试管中加入300mg 2-(4-溴苯)异吲哚啉-1,3-二酮(1mmol),10mg叔丁醇锂,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品295mg,收率98%。
白色固体。1H NMR(600MHz,T-MeOD)δ7.83-7.81(m,1H),7.72-7.70(m,4H),7.62-7.58 (m,3H),6.46(s,1H),4.60(s,3H).13C NMR(150MHz,T-MeOD)δ168.34,145.56,137.78,134.31,132.95,132.44,131.07,125.88,124.69,124.32,119.50,84.05.
实施例20
在带磁子的玻璃试管中加入241mg 2-(3-氟苯)异吲哚啉-1,3-二酮(1mmol),11mg叔丁醇钾,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品237mg,收率97%。
白色固体。1H NMR(400MHz,T-MeOD)δ7.84-7.82(m,1H),7.73-7.70(m,2H),7.69-7.67 (m,1H),7.63-7.60(m,2H),7.47-7.43(m,1H),7.00-6.97(m,1H),6.49(s,1H).13C NMR(101 MHz,CDCl3)δ168.39,165.10,163.49,145.54,140.38,140.31,134.38,132.43,131.26,131.20, 131.08,124.70,124.36,119.21,119.19,112.88,112.74,110.87,110.70,84.07.
实施例21
在带磁子的玻璃试管中加入357mg 2-(4-氯苯)异吲哚啉-1,3-二酮(1mmol),10mg叔丁醇锂,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品251mg,收率97%。
白色固体。1H NMR(600MHz,d6-DMSO)δ7.84-7.82(m,2H),7.78-7.77(m,1H),7.74-7.72 (m,1H),7.69-7.68(m,1H),7.62-7.60(m,1H),7.51-7.50(m,2H),6.92-6.91(m,1H),6.53(d,J= 4.0Hz,1H).13C NMR(150MHz,d6-DMSO)δ165.56,144.29,136.48,133.01,131.05,129.82, 128.65,128.57,123.72,123.54,122.98,81.95.
实施例22
在带磁子的玻璃试管中加入241mg 2-(4-氟苯)异吲哚啉-1,3-二酮(1mmol),11mg叔丁醇钾,氮气保护下加入2毫升异丙醇,加入2微升0.01M的催化剂(S/C=50,000),充入4MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品238mg,收率98%。
白色固体。1H NMR(600MHz,T-MeOD)δ7.82-7.81(m,1H),7.72-7.69(m,4H),7.62-7.59 (m,1H),7.21-7.18(m,2H),6.40(s,1H).13C NMR(150MHz,CDCl3)δ168.50,162.87,161.25, 145.70,134.46,134.44,134.16,132.51,131.00,127.16,127.10,124.69,124.26,116.64,116.49, 84.56.
实施例23
在带磁子的玻璃试管中加入175mg 1-苯基吡咯烷-2,5-二酮(1mmol),5.6mg氢氧化钾,氮气保护下加入2毫升四氢呋喃,加入5微升0.01M的催化剂(S/C=20,000),充入2MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品170mg,收率96%。
白色固体。1H NMR(600MHz,CDCl3)δ7.13-7.31(m,5H),5.82-5.89(m,1H),2.12-7.49(m, 4H).13C NMR(150MHz,CDCl3)δ174.91,137.32,128.95,128.08,127.54,81.87,27.78,25.90.
实施例24
在带磁子的玻璃试管中加入323mg 1-萘基-苯并异吲哚啉-1,3-二酮(1mmol),4.0mg氢氧化钠,氮气保护下加入2毫升四氢呋喃,加入2微升0.01M的催化剂(S/C=50,000),充入2MPa氢气,40℃反应24小时。反应结束后,自然冷却至室温,小心放掉氢气,硅藻土过滤,滤液脱去有机溶剂后得产品315mg,收率97%。
白色固体。1H NMR(400MHz,d6-DMSO)δ8.38-8.01(m,4H),7.73-7.55(m,4H),7.46-6.99 (m,2H),7.23-7.19(m,3H),6.84(s,1H).13C NMR(101MHz,CDCl3)δ167.01,142.74,136.21, 134.32,132.42,133.63,133.05,129.04,128.67,128.31,127.83,127.63,127.12,126.16,125.89, 125.34,124.75,121.02,119.07,104.09,91.8。
Claims (10)
3.根据权利1所述的制备方法,所述的溶剂为异丙醇、四氢呋喃、甲苯的一种或者任意比例的混合物。
4.根据权利1所述的制备方法,所述的碱为叔丁醇钾、叔丁醇钠、叔丁醇锂、氢氧化钾、氢氧化钠、碳酸钠、碳酸钾、碳酸铯的一种或者任意比例混合物。
5.根据权利1或2所述的制备方法,所述催化剂与环状酰亚胺的比例为1∶20,000-50,000。
6.根据权利1或3所述的制备方法,所述的溶剂为异丙醇。
7.根据权利1或4所述的制备方法,所述的碱为叔丁醇钾,所述碱与环状酰亚胺的比例为1∶10-50。
8.根据权利1所述的制备方法,所述均相催化氢化反应的温度为20-80摄氏度,更优选40-60摄氏度。
9.根据权利1所述的制备方法,所述均相催化氢化反应的氢气压力为4-6MPa。
10.根据权利1所述的制备方法,所述均相催化氢化反应的时间为20-25小时。
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HUIFANG NIE ET AL.: "Asymmetric hydrogenation of aromatic ketones using an iridium(I) catalyst containing ferrocene-based P–N–N tridentate ligands", 《TETRAHEDRON: ASYMMETRY》 * |
SATOSHI TAKEBAYASHI ET AL.: "Desymmetrization of meso-Cyclic Imides via Enantioselective Monohydrogenation", 《J. AM. CHEM. SOC.》 * |
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