CN113773244A - Method for removing ketone fragment in nitrogen heterocyclic compound substituent - Google Patents
Method for removing ketone fragment in nitrogen heterocyclic compound substituent Download PDFInfo
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- CN113773244A CN113773244A CN202110366443.2A CN202110366443A CN113773244A CN 113773244 A CN113773244 A CN 113773244A CN 202110366443 A CN202110366443 A CN 202110366443A CN 113773244 A CN113773244 A CN 113773244A
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- 238000000034 method Methods 0.000 title claims abstract description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 26
- 125000000468 ketone group Chemical group 0.000 title claims abstract 3
- 238000007327 hydrogenolysis reaction Methods 0.000 claims abstract description 22
- 229910052761 rare earth metal Inorganic materials 0.000 claims abstract description 19
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 150000002910 rare earth metals Chemical class 0.000 claims abstract description 7
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910000077 silane Inorganic materials 0.000 claims abstract description 4
- 230000003197 catalytic effect Effects 0.000 claims abstract description 3
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims abstract 3
- 150000003333 secondary alcohols Chemical class 0.000 claims abstract 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- 239000003054 catalyst Substances 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- 238000012546 transfer Methods 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- 229910052684 Cerium Inorganic materials 0.000 claims description 2
- 229910052692 Dysprosium Inorganic materials 0.000 claims description 2
- 229910052691 Erbium Inorganic materials 0.000 claims description 2
- 229910052693 Europium Inorganic materials 0.000 claims description 2
- 229910052688 Gadolinium Inorganic materials 0.000 claims description 2
- 229910052689 Holmium Inorganic materials 0.000 claims description 2
- 229910052765 Lutetium Inorganic materials 0.000 claims description 2
- 229910052779 Neodymium Inorganic materials 0.000 claims description 2
- 229910052777 Praseodymium Inorganic materials 0.000 claims description 2
- 229910052772 Samarium Inorganic materials 0.000 claims description 2
- 229910052771 Terbium Inorganic materials 0.000 claims description 2
- 229910052775 Thulium Inorganic materials 0.000 claims description 2
- 229910052769 Ytterbium Inorganic materials 0.000 claims description 2
- 229910052746 lanthanum Inorganic materials 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
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910052706 scandium Inorganic materials 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 11
- 125000001424 substituent group Chemical group 0.000 abstract description 9
- 229930014626 natural product Natural products 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 4
- 238000013461 design Methods 0.000 abstract description 2
- -1 diaryl methanol compound Chemical class 0.000 description 22
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 150000002576 ketones Chemical group 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- ZLKXXTNOBAOGCJ-UHFFFAOYSA-N 2-(quinolin-2-ylmethyl)quinoline Chemical compound C1=CC=CC2=NC(CC=3N=C4C=CC=CC4=CC=3)=CC=C21 ZLKXXTNOBAOGCJ-UHFFFAOYSA-N 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- GMPCGXKPIWOZTM-UHFFFAOYSA-N 2-(1-benzothiophen-2-ylmethyl)-1-benzothiophene Chemical compound C1=CC=C2SC(CC=3SC4=CC=CC=C4C=3)=CC2=C1 GMPCGXKPIWOZTM-UHFFFAOYSA-N 0.000 description 4
- JVYGSYTXAREMJK-UHFFFAOYSA-N 2-(pyridin-2-ylmethyl)pyridine Chemical compound C=1C=CC=NC=1CC1=CC=CC=N1 JVYGSYTXAREMJK-UHFFFAOYSA-N 0.000 description 4
- 150000004030 azacyclic compounds Chemical class 0.000 description 4
- QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- 238000004904 shortening Methods 0.000 description 3
- KEHOIBBPRFRZFW-UHFFFAOYSA-N 4-propan-2-yl-2-[(4-propan-2-yl-4,5-dihydro-1,3-oxazol-2-yl)methyl]-4,5-dihydro-1,3-oxazole Chemical compound CC(C)C1COC(CC=2OCC(N=2)C(C)C)=N1 KEHOIBBPRFRZFW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- NJBCRXCAPCODGX-UHFFFAOYSA-N 2-methyl-n-(2-methylpropyl)propan-1-amine Chemical compound CC(C)CNCC(C)C NJBCRXCAPCODGX-UHFFFAOYSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- IUHFWCGCSVTMPG-UHFFFAOYSA-N [C].[C] Chemical class [C].[C] IUHFWCGCSVTMPG-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- YBRNUJSXEIBYFU-UHFFFAOYSA-N hydroxy(phenyl)silane Chemical compound O[SiH2]C1=CC=CC=C1 YBRNUJSXEIBYFU-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000001420 substituted heterocyclic compounds Chemical class 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/127—Preparation from compounds containing pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D263/12—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention belongs to the technical field of chemical industry, and relates to a method for hydrogenolysis of a non-tension nonpolar carbon-carbon single bond on a nitrogen heterocyclic side chain, in particular to a simple method for removing a ketone fragment in a nitrogen heterocyclic compound substituent. In the invention, under a rare earth catalytic system, secondary alcohol or secondary amine or silane is used as a hydrogen source to realize the method for highly selectively transferring and hydrogenolyzing the nitrogen heterocyclic side chain carbon-carbon single bond, wherein the reaction can not be or is difficult to realize by other known methods; the method provides a new strategy for the structure simplification of complex natural products and the reverse synthetic route design of organic synthesis, and can be widely applied; the method has the advantages of good atom economy, simple and convenient operation, controllable position selectivity, chemical selectivity and the like, and provides a practical new method for simplifying the side chain substituent of the nitrogen heterocyclic ring.
Description
Technical Field
The invention belongs to the technical field of chemical industry, and relates to a method for hydrogenolysis of a non-tension nonpolar carbon-carbon single bond of a nitrogen heterocyclic side chain, in particular to a simple method for removing a ketone fragment in a nitrogen heterocyclic substituent, especially a method for shortening a carbon chain of the nitrogen heterocyclic substituent.
Background
The prior art discloses that nitrogen heterocyclic ring structural units are widely present in the molecular structures of natural products and bulk chemical products. In research practice, modification of ring substituents is often required to modulate their biological activity and functional properties, however, traditional methods of modifying nitrogen heterocycles have been largely limitedBased on C-H activation or derivatization of existing functional groups, a new functional substituent is introduced. In contrast, methods for shortening azacyclic side chains have been reported to be less, primarily limited to the cleavage of carbon-heteroatom bonds or the cleavage of heteroatom-substituted carbon-carbon bonds. So far, reports on partial fragment cutting of nitrogen heterocyclic substituent directly through fat non-activated carbon-carbon single bond hydrogenolysis reaction are not seen. The reason for this is mainly due to selective cleavage of the side chain C (sp)3)-C(sp3) Bonds are more challenging than extending carbon chains, and there is no effective general method (Science 2019,364, 681-685; nature 2020,580, 621-627). Hydrogenolysis of nonpolar, non-activated C (sp)3)-C(sp3) The bond tends to result in preferential cleavage of the carbon-nitrogen bond (Nature Commun.2017,8,1866). Therefore, the selective cleavage of C (sp) has been developed3)-C(sp3) The method of bonding, whether it is for structural optimization of natural products or for the design of routes for organic synthesis, will have a major impact (Nature 2018,564, 244-248; nature 2016,537, 214-219). Carbonyl groups are widely found in natural products and organic synthetic molecules and are readily introduced by various conventional reaction routes. It has been shown that the removal of a part of the ketone structural unit in the side chain substituent of the natural heterocyclic compound not only can effectively improve the activity of the natural product, but also can reduce the toxicity of the natural product by the strategy (chem.Rev.2019,119, 4180-4220). Unfortunately, due to the lack of methods for removing ketone building blocks from organic molecules, structurally simplified analogs of such natural products now have to be synthesized using multistep processes or de novo synthetic strategies, which not only reduce the atom economy of synthesis of the target molecule, but are also time-consuming and laborious (J.Am.chem.Soc.2010,132, 1432-1442; J.Am.chem.Soc.2004,126, 1038-1040). Through C (sp)3)-C(sp3) The main reason why the removal of the ketone structural unit by the bond reduction reaction is difficult is that the carbonyl ratio is C (sp)3)-C(sp3) The bond is more easily reduced. Therefore, there is an urgent need to develop a C (sp) having high selectivity away from carbonyl group3)-C(sp3) Bond hydrogenolysis strategies.
Based on the current state of the art, the inventors of the present application propose to provide a method for hydrogenolysis of a non-strained non-polar carbon-carbon single bond on a side chain of an azacyclic compound, and in particular, to a simple method for removing a ketone fragment from a substituent of an azacyclic compound.
Disclosure of Invention
The invention aims to provide a method for hydrogenolysis of a non-tension non-polar carbon-carbon single bond on a side chain of an azacyclic compound based on the current situation of the prior art, and particularly relates to a simple method for removing a ketone fragment in a substituent of the azacyclic compound.
The invention provides a method for obtaining a novel substituted heterocyclic compound by using a compound shown as a formula (I) as a raw material and a diaryl methanol compound as a hydrogen source and carrying out high-selectivity hydrogenolysis on a carbon-carbon single bond on a side chain of an azacyclo. The method has the advantages of good atomic economy, simple and convenient operation and the like.
The invention provides a method for hydrogenolysis of a branched carbon-carbon single bond of an azacyclo, in particular to a simple method for removing a ketone fragment in a substituent of an azacyclo compound, which comprises the following steps:
under the protection of nitrogen, in a rare earth catalytic system, taking a compound shown as a formula (I) as a reactant, taking diaryl methanol or secondary amine or silane as a hydrogen source, and carrying out selective hydrogenolysis on a carbon-carbon single bond far away from a carbonyl group to obtain hydrogenolysis products (II) and (III); the reaction formula is as follows:
in the above formula, representative heterocycles have been listed therein;
the catalyst is a rare earth alkyl complex, a rare earth aryl complex, a rare earth amino complex, a rare earth alkoxy complex, a rare earth sulfenyl complex, a rare earth amidino complex and the like;
the rare earth metals are Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu;
the solvent is benzene, toluene, xylene, tetrahydrofuran and hexane;
the hydrogen source comprises: diarylcarbinols, secondary amines, hydrosilanes; the hydrogen source is preferably: diaryl carbinols, aryl silanes;
calculated according to molar ratio: the ratio of the compound of the formula (I) to the rare earth catalyst is 1/0.005-0.30, and the ratio of the compound of the formula (I) to the hydrogen source is 1/0.5-2.0;
the reaction temperature of the transfer hydrogenolysis compound (I) is 0-120 ℃;
the reaction time of the transfer hydrogenolysis compound (I) is 2-48 h.
The invention relates to a method for shortening side chain substituent of nitrogen heterocyclic compound by hydrogenolysis reaction of non-tension nonpolar carbon-carbon single bond. Compared with the existing process route, the method has the following advantages:
1) the raw material (the compound of formula (I)) and the hydrogen source are widely available or easy to prepare;
2) directly removing ketone fragments of heterocyclic substituent groups through carbon-carbon bond hydrogenolysis reaction, and providing a convenient way for synthesizing another substituted nitrogen heterocyclic ring from one substituted nitrogen heterocyclic ring;
3) the conventional reactivity reversal of the ketone is controlled by the catalyst, so that the reduction of the carbon-carbon single bond-preferential carbonyl is realized for the first time;
4) the protection of carbonyl in the hydrogenolysis process of the carbon-carbon bond is avoided, a large amount of reaction reagents and reaction steps are saved, and the economy and the atom economy are good;
4) the method has the advantages of simple operation, mild reaction conditions, strong reaction selectivity, high product yield, simple preparation process and product separation and purification, and good application prospect.
Compared with the prior art, the invention has the beneficial effects that:
the method can directly cut off the inert carbon-carbon single bond to obtain a corresponding carbon-carbon bond hydrogenolysis product; side chain simplification of numerous types of nitrogen heterocyclic compounds that are otherwise impossible or difficult to achieve is successfully achieved; realizing gram-grade carbon-carbon bond hydrogenolysis reaction; in addition, functional group compatibility is good; the reaction condition is mild, the product is convenient to separate and purify, and the process operation is simple and convenient.
Detailed Description
The present invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.
Example 1
Synthesis of bis (2-pyridyl) methane in one step from 1, 3-diphenyl-4, 4-bis (2-pyridyl) -1-butanone:
under the protection of nitrogen, 1, 3-diphenyl-4, 4-di (2-pyridyl) -1-butanone (0.50mmol), diphenylmethanol (0.50mmol) and catalyst Y [ N (SiMe)3)2]3(2 mol%) was dissolved in 2mL of toluene and reacted at 110 ℃ for 12 hours, and the isolated yield of the product, bis (2-pyridyl) methane, was 85%.
1H NMR(400MHz,CDCl3)δ(ppm)8.58–8.45(m,2H),7.58(t,J＝7.6Hz,2H),7.24(d,J＝7.7Hz,2H),7.11(t,J＝6.5Hz,2H),4.32(s,2H)。
Example 2
Synthesis of bis (2-quinolinyl) methane in one step from 1, 3-diphenyl-4, 4-bis (2-quinolinyl) -1-butanone:
under the protection of nitrogen, raw materials of 1, 3-diphenyl-4, 4-di (2-quinolyl) -1-butanone (0.50mmol), 4-methoxyphenyl benzyl alcohol (0.80mmol) and a catalyst La [ N (SiMe)3)2]3(5 mol%) was dissolved in 2mL of toluene and reacted at 80 ℃ for 24 hours, and the isolated yield of the product, bis (2-quinolyl) methane, was 89%.
1H NMR(400MHz,CDCl3)δ(ppm)8.11(d,J＝8.5Hz,2H),8.02(d,J＝8.4Hz,2H),7.74(d,J＝8.2Hz,2H),7.70(t,J＝7.7Hz,2H),7.49(t,J＝7.4Hz,2H),7.40(d,J＝8.4Hz,2H),4.73(s,2H)。
Example 3
Synthesis of bis (2-benzothienyl) methane in one step from 1, 3-diphenyl-4, 4-bis (2-benzothiazolyl) -1-butanone:
under the protection of nitrogenRaw materials of 1, 3-diphenyl-4, 4-bis (2-benzothiazolyl) -1-butanone (0.50mmol), phenylsilane (0.60mmol) and a catalyst Sm (SPh)3(5 mol%) is dissolved in 2mL xylene and reacted at 110 ℃ for 12h, and the product, bis (2-benzothienyl) methane, is isolated in 59% yield.
1H NMR(400MHz,CDCl3)δ(ppm)8.07(d,J＝7.2Hz,2H),7.87(d,J＝7.9Hz,2H),7.51(t,J＝7.6Hz,2H),7.41(t,J＝7.5Hz,2H),4.98(s,2H)。
Example 4
Synthesis of bis (4-isopropyl-4, 5-dihydrooxazolyl) methane from 1, 3-diphenyl-4, 4-bis (4-isopropyl-4, 5-dihydrooxazolyl) -1-butanone in one step:
under the protection of nitrogen, raw materials of 1, 3-diphenyl-4, 4-di (4-isopropyl-4, 5-dihydrooxazolyl) -1-butanone (0.5mmol), diisobutylamine (0.55mmol) and catalyst YPh3(5 mol%) is dissolved in 2mL toluene, and the reaction is carried out for 12h at 100 ℃, and the separation yield of the product bis (4-isopropyl-4, 5-dihydrooxazolyl) methane is 54%.
1H NMR(400MHz,CDCl3)δ(ppm)4.25(t,J＝8.5Hz,2H),4.02–3.84(m,4H),3.32–3.26(m,2H),1.78–1.70(m,2H),0.93(d,J＝6.7Hz,6H),0.85(d,J＝6.8Hz,6H)；
Example 5
Synthesis of bis (2-quinolinyl) methane in one step from (E) -1, 5-diphenyl-6, 6-bis (2-quinolinyl) -3-alkenyl-1-pentanone:
under the protection of nitrogen, raw material (E) -1, 5-diphenyl-6, 6-di (2-quinolyl) -3-alkenyl-1-pentanone (0.50mmol), diphenylmethanol (0.40mmol) and catalyst Y (OCHPh)2)3(3 mol%) was dissolved in 2mL of tetrahydrofuran and reacted at 80 ℃ for 24 hours, and the isolated yield of the product, bis (2-quinolyl) methane, was 73%.
1H NMR(400MHz,CDCl3)δ(ppm)8.11(d,J＝8.5Hz,2H),8.02(d,J＝8.4Hz,2H),7.74(d,J＝8.2Hz,2H),7.70(t,J＝7.7Hz,2H),7.49(t,J＝7.4Hz,2H),7.40(d,J＝8.4Hz,2H),4.73(s,2H)。
Example 6
Synthesis of bis (2-benzothienyl) methane in one step from (E) -1, 5-diphenyl-6, 6-bis (2-benzothiazolyl) -3-alkenyl-1-pentanone:
under the protection of nitrogen, raw material (E) -1, 5-diphenyl-6, 6-bis (2-benzothiazolyl) -3-alkenyl-1-pentanone (0.50mmol), diphenyl methanol (0.52mmol) and catalyst Y [ N (SiMe)3)2]3(1 mol%) was dissolved in 2mL of toluene and reacted at 110 ℃ for 6 hours, and the isolated yield of the product, bis (2-benzothienyl) methane, was 84%.
1H NMR(400MHz,CDCl3)δ(ppm)8.07(d,J＝7.2Hz,2H),7.87(d,J＝7.9Hz,2H),7.51(t,J＝7.6Hz,2H),7.41(t,J＝7.5Hz,2H),4.98(s,2H)
Example 7
One-step synthesis of bis (2-pyridyl) methane from 1-tert-butyl-3-phenyl-bis (2-pyridyl) -1-butanone:
under the protection of nitrogen, raw materials of 1-tert-butyl-3-phenyl-di (2-pyridyl) -1-butanone (0.50mmol), diphenylmethanol (0.55mmol) and a catalyst Y [ N (SiMe)3)2]3(5 mol%) was dissolved in 2mL of toluene and reacted at 110 ℃ for 6 hours, and the isolated yield of bis (2-pyridyl) methane was 78%.
1H NMR(400MHz,CDCl3)δ(ppm)8.58–8.45(m,2H),7.58(t,J＝7.6Hz,2H),7.24(d,J＝7.7Hz,2H),7.11(t,J＝6.5Hz,2H),4.32(s,2H)。
Example 8
One-step synthesis of bis (2-quinolinyl) methane from 1-tert-butyl-3-phenyl-bis (2-quinolinyl) -1-butanone:
under the protection of nitrogen, raw material 1-tert-butyl-3-phenyl-di (2-quinolyl) -1-butanone (0.50mmol), phenylsilanol (2.0mmol) and catalyst Yb [ CH ]2(TMS)]3(10 mol%) was dissolved in 2mL of toluene and reacted at 100 ℃ for 48 hours, and the isolated yield of bis (2-quinolyl) methane was 65%.
1H NMR(400MHz,CDCl3)δ(ppm)8.11(d,J＝8.5Hz,2H),8.02(d,J＝8.4Hz,2H),7.74(d,J＝8.2Hz,2H),7.70(t,J＝7.7Hz,2H),7.49(t,J＝7.4Hz,2H),7.40(d,J＝8.4Hz,2H),4.73(s,2H)。
Although the present invention has been described in detail with reference to the preferred embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (5)
1. A method for removing a ketone fragment from a nitrogen heterocyclic compound substituent, comprising the steps of:
under the protection of nitrogen, under a rare earth catalytic system, taking a compound shown as a formula (I) as a reaction substrate, taking alcohol or secondary amine or silane as a hydrogen source, and obtaining hydrogenolysis products (II) and (III) by selectively carrying out hydrogenolysis on a carbon-carbon single bond far away from a carbonyl group; the reaction formula is as follows:
in the above formula, representative heterocycles are listed in the formula;
the catalyst is a rare earth alkyl complex, a rare earth aryl complex, a rare earth amino complex, a rare earth alkoxy complex, a rare earth sulfenyl complex or a rare earth amidino complex;
the rare earth metal is Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb or Lu;
the solvent is benzene, toluene, xylene, tetrahydrofuran or hexane;
the hydrogen source comprises: secondary alcohol, secondary amine, silane.
2. The method of claim 1, wherein the hydrogen source is: diarylcarbinols or arylsilanes.
3. The method according to claim 1, wherein the method comprises, in terms of mole ratios: the ratio of the compound of formula (I)/rare earth catalyst is 1/0.005-0.30, and the ratio of the compound of formula (I)/hydrogen source is 1/0.5-2.0.
4. The process according to claim 1, wherein the reaction temperature for the transfer hydrogenolysis of compound (I) is between 0 ℃ and 120 ℃.
5. The process according to claim 1, wherein the reaction time for the transfer hydrogenolysis of compound (I) is 2 to 48 h.
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