CN113773244B - 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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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 35
- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 31
- 125000000468 ketone group Chemical group 0.000 title claims abstract 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 17
- 238000007327 hydrogenolysis reaction Methods 0.000 claims abstract description 15
- 229910052761 rare earth metal Inorganic materials 0.000 claims abstract description 13
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 150000002910 rare earth metals Chemical class 0.000 claims abstract description 8
- -1 diaryl methanol Chemical compound 0.000 claims description 27
- 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 14
- 150000001875 compounds Chemical class 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 229910000077 silane Inorganic materials 0.000 claims description 3
- 239000002904 solvent Substances 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
- 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
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 12
- 229930014626 natural product Natural products 0.000 abstract description 7
- 125000001424 substituent group Chemical group 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 4
- 238000013461 design Methods 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 150000003333 secondary alcohols Chemical class 0.000 abstract 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 10
- 150000002576 ketones Chemical group 0.000 description 10
- 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
- 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
- 238000003776 cleavage reaction Methods 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
- 230000007017 scission Effects 0.000 description 4
- 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 3
- 238000000926 separation method 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
- 238000010504 bond cleavage reaction Methods 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
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- LYTMVABTDYMBQK-UHFFFAOYSA-N 2-benzothiophene Chemical compound C1=CC=CC2=CSC=C21 LYTMVABTDYMBQK-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- IUHFWCGCSVTMPG-UHFFFAOYSA-N [C].[C] Chemical class [C].[C] IUHFWCGCSVTMPG-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 238000013459 approach Methods 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
- 230000003197 catalytic 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
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons 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
- 238000005457 optimization Methods 0.000 description 1
- 230000037361 pathway Effects 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
- 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
- 229910052706 scandium Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000001420 substituted heterocyclic compounds Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 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
- 229910052727 yttrium Inorganic materials 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, relates to a method for hydrogenolyzing nonpolar carbon-carbon single bonds of nitrogen heterocyclic side chains, and in particular relates to a simple method for removing ketone fragments in nitrogen heterocyclic compound substituents. The invention uses secondary alcohol or secondary amine or silazane as hydrogen source to realize high-selectivity transfer hydrogenolysis nitrogen heterocyclic side chain carbon-carbon single bond method under rare earth catalysis system, wherein the reaction is not realized or is difficult to realize by other known methods; the method provides a new strategy for the structural simplification of complex natural products and the design of an inverse synthetic route of organic synthesis, and can be widely applied; the method has the advantages of good atom economy, simple and convenient operation, controllable position selectivity and chemical selectivity and the like, and provides a practical novel method for simplifying the nitrogen heterocycle side chain substituent.
Description
Technical Field
The invention belongs to the technical field of chemical industry, relates to a method for hydrogenolyzing nonpolar carbon-carbon single bonds of nitrogen heterocyclic side chains, in particular to a simple method for removing ketone fragments in nitrogen heterocyclic compound substituents, and especially relates to a method for shortening carbon chains of nitrogen heterocyclic compound substituents.
Background
The prior art discloses that nitrogen heterocyclic structural units are widely present in the molecular structure of natural products and bulk chemical products. In research practice, modification of ring substituents is often required to regulate their biological activity and functional properties, however, traditional methods of modifying nitrogen heterocyclic compounds are mainly based on c—h activation or derivatization of existing functional groups, introducing new functional substituents. In contrast, the shortened nitrogen heterocyclic side chain approach is less reported and is primarily limited to carbon-heteroatom bond cleavage or heteroatom-substituted carbon-carbon bond cleavage. There has been no report so far on cleavage of a partial fragment of an azacyclic substituent directly by aliphatic non-activated carbon-carbon single bond hydrogenolysis reaction. The reason for this is mainly due to selective cleavage of side chain C (sp 3 )-C(sp 3 ) Bonds are more challenging than elongating carbon chains, and there is no effective general method (Science 2019,364,681-685; nature 2020,580,621-627). Hydrogenolysis of non-polar non-activated C (sp) 3 )-C(sp 3 ) The bond tends to cause preferential cleavage of the carbon-nitrogen bond (Nature Commun.2017,8,1866). Thus, the selective cleavage of C (sp 3 )-C(sp 3 ) The method of bonding will have an important impact both on the structural optimization of natural products and on the route design of organic synthesis (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 a variety of conventional reaction pathways. It has been shown that removal of part of the ketone building blocks in the side chain substituents of the natural heterocyclic compounds not only effectively increases the activity of the natural products, but also reduces the toxicity of the natural products by this strategy (chem. Rev.2019,119, 4180-4220). Unfortunately, due to the lack of methods for removing ketone building blocks from organic molecules, structurally simplified analogues of such natural products now have to be synthesized using either multi-step processes or de novo synthesis strategies, which not only reduce the atomic economy of target molecule synthesis, but are also time-consuming and laborious (J.am. Chem. Soc.2010,132,1432-1442; J.am. Chem. Soc.2004,126, 1038-1040). By C (sp) 3 )-C(sp 3 ) The bond reduction reaction to remove the ketone building block is difficult, mainly due to the carbonyl to C (sp 3 )-C(sp 3 ) The bond is more easily reduced. Thus, there is an urgent need to develop a C (sp 3 )-C(sp 3 ) Bond hydrogenolysis strategy.
Based on the state of the art, the inventors of the present application have sought to provide a method for hydrogenolysis of non-strained nonpolar carbon-carbon single bonds of nitrogen heterocyclic side chains, in particular to a simple method for removing ketone fragments from nitrogen heterocyclic compound substituents.
Disclosure of Invention
The invention aims to provide a method for hydrogenolyzing nonpolar carbon-carbon single bonds of nitrogen heterocyclic side chains, in particular to a simple method for removing ketone fragments in nitrogen heterocyclic compound substituents.
The invention provides a method for obtaining a novel substituted heterocyclic compound by taking a compound shown in a formula (I) as a raw material and taking a diaryl methanol compound as a hydrogen source and hydrogenolyzing a carbon-carbon single bond of an azacyclic side chain with high selectivity. The method has the advantages of good atom economy, simple operation and the like.
The invention provides a method for hydrogenolysis of nitrogen heterocyclic branched carbon-carbon single bonds, in particular to a simple method for removing ketone fragments in nitrogen heterocyclic compound substituents, which comprises the following steps:
in a rare earth catalytic system under the protection of nitrogen, taking a compound shown in a formula (I) as a reactant, taking diaryl methanol or secondary amine or silane as a hydrogen source, and obtaining hydrogenolysis products (II) and (III) by selectively hydrogenolyzing a carbon-carbon single bond far away from carbonyl; the reaction formula is as follows:
in the above formula, representative heterocycles are listed therein;
the catalyst is rare earth alkyl complex, rare earth aryl complex, rare earth amino complex, rare earth alkoxy complex, rare earth hydrocarbon sulfur-based complex, rare earth amidino complex and the like;
the rare earth metal is Sc, Y, la, ce, pr, nd, sm, eu, gd, tb, dy, ho, er, tm, yb, lu;
the solvent is benzene, toluene, xylene, tetrahydrofuran or hexane;
the hydrogen source includes: diaryl methanol, secondary amines, silazanes; the hydrogen source is preferably: diaryl methanol, aryl silane;
calculated according to the mole ratio: the compound of formula (I)/rare earth catalyst is 1/0.005-0.30, and the compound of formula (I)/hydrogen source is 1/0.5-2.0;
the reaction temperature for transferring the hydrogenolysis compound (I) is 0-120 ℃;
the reaction time for transferring the hydrogenolysis compound (I) is 2-48 hours.
The method for shortening the side chain substituent of the nitrogen heterocyclic compound through hydrogenolysis reaction of non-tension nonpolar carbon-carbon single bond. Compared with the existing process route, the method has the following advantages:
1) The source of the raw materials (the compound of formula (I)) and the hydrogen source are wide or easy to prepare;
2) The direct removal of ketone fragments of heterocyclic substituents by carbon-carbon bond hydrogenolysis provides a convenient route for synthesizing one substituted nitrogen heterocycle from another;
3) The conventional reactivity reversal of ketone is controlled by the catalyst, so that the reduction of the carbonyl group with the carbon-carbon single bond priority is realized for the first time;
4) The protection of carbonyl in the hydrogenolysis process of carbon-carbon bonds is avoided, a large number of reaction reagents and reaction steps are saved, and the economy and 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 be used for directly cutting off the inert carbon-carbon single bond to obtain the corresponding carbon-carbon bond hydrogenolysis product; side chain simplification of numerous types of aza heterocyclic compounds that are otherwise not or hardly achievable has been successfully achieved; realizing gram-grade carbon-carbon bond hydrogenolysis reaction; in addition, the compatibility of the functional groups is good; the reaction condition is mild, the separation and purification of the product are convenient, and the process operation is simple.
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
One-step synthesis of bis (2-pyridyl) methane from 1, 3-diphenyl-4, 4-bis (2-pyridyl) -1-butanone:
1, 3-diphenyl-4, 4-bis (2-pyridyl) -1-butanone (0.50 mmol), benzhydrol (0.50 mmol) 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%.
1 H NMR(400MHz,CDCl 3 )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
One-step synthesis of bis (2-quinolinyl) methane from 1, 3-diphenyl-4, 4-bis (2-quinolinyl) -1-butanone:
under the protection of nitrogen, the raw material 1, 3-diphenyl-4, 4-di (2-quinolyl) -1-butanone (0.50 mmol), 4-methoxy phenyl benzyl alcohol (0.80 mmol) 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-quinolinyl) methane was 89%.
1 H NMR(400MHz,CDCl 3 )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
One-step synthesis of bis (2-benzothienyl) methane from 1, 3-diphenyl-4, 4-bis (2-benzothiazolyl) -1-butanone:
under the protection of nitrogen, the raw material 1, 3-diphenyl-4, 4-bis (2-benzothiazolyl) -1-butanone (0.50 mmol), phenylsilane (0.60 mmol) and a catalyst Sm (SPh) 3 (5 mol%) was dissolved in 2mL of xylene and reacted at 110℃for 12 hours, and the product bis (2-benzothienyl) methane was isolated in 59% yield.
1 H NMR(400MHz,CDCl 3 )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
One-step synthesis of bis (4-isopropyl-4, 5-dihydro-oxazolyl) methane from 1, 3-diphenyl-4, 4-bis (4-isopropyl-4, 5-dihydro-oxazolyl) -1-butanone:
under the protection of nitrogen, the air conditioner is provided with a nitrogen inlet,raw material 1, 3-diphenyl-4, 4-di (4-isopropyl-4, 5-dihydro oxazolyl) -1-butanone (0.5 mmol), diisobutylamine (0.55 mmol) and catalyst YPh 3 (5 mol%) was dissolved in 2mL of toluene and reacted at 100℃for 12 hours, and the product bis (4-isopropyl-4, 5-dihydro-oxazolyl) methane was isolated in 54% yield.
1 H NMR(400MHz,CDCl 3 )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
One-step synthesis of bis (2-quinolinyl) methane 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 (0.50 mmol), benzhydrol (0.40 mmol) and catalyst Y (OCHPh) 2 ) 3 (3 mol%) was dissolved in 2mL of tetrahydrofuran and reacted at 80℃for 24 hours, and the product bis (2-quinolinyl) methane was isolated in 73% yield.
1 H NMR(400MHz,CDCl 3 )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
One-step synthesis of bis (2-benzothienyl) methane from (E) -1, 5-diphenyl-6, 6-bis (2-benzothiazolyl) -3-alkenyl-1-pentanone:
under nitrogen, starting material (E) -1, 5-diphenyl-6, 6-bis (2-benzothiazolyl) -3-alkenyl-1-pentanone (0.50 mmol), benzhydrol (0.52 mmol) and catalyst Y [ N (SiMe 3 ) 2 ] 3 (1 mol%) was dissolved in 2mL of toluene and reacted at 110℃for 6 hours to give bis (2-benzothiophene)Radical) methane separation yield 84%.
1 H NMR(400MHz,CDCl 3 )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, the raw material 1-tertiary butyl-3-phenyl-di (2-pyridyl) -1-butanone (0.50 mmol), benzhydrol (0.55 mmol) 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 yield of bis (2-pyridyl) methane was 78%.
1 H NMR(400MHz,CDCl 3 )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, the raw material 1-tertiary butyl-3-phenyl-di (2-quinolyl) -1-butanone (0.50 mmol), phenylsilanol (2.0 mmol) 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 di (2-quinolinyl) methane was 65%.
1 H NMR(400MHz,CDCl 3 )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)。
The above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered by the scope of the claims of the present invention.
Claims (4)
1. A method for removing a ketone fragment from a nitrogen heterocyclic compound substituent, comprising the steps of: under the protection of nitrogen, using a rare earth catalyst, taking a compound shown in a formula (I) as a reaction substrate, taking diaryl methanol or aryl silane as a hydrogen source, and obtaining hydrogenolysis products (II) and (III) by selectively hydrogenolyzing carbon-carbon single bonds far away from carbonyl in the presence of a solvent; the reaction formula is as follows:
r=alkyl, aryl or heteroaryl
R 1 ,R 2 ,R 3 =aryl or heteroaryl;
n＝0-2；
the rare earth catalyst is Y [ N (SiMe) 3 ) 2 ] 3 、La[N(SiMe 3 ) 2 ] 3 、Sm(SPh) 3 、YPh 3 、Y(OCHPh 2 ) 3 ；
The solvent is benzene, toluene, xylene, tetrahydrofuran or hexane.
2. The method according to claim 1, wherein in the method, the molar ratio is calculated: the dosage ratio of the compound of the formula (I) to the rare earth catalyst is 1:0.005-0.30, the ratio of the compound of formula (I) to the hydrogen source being 1:0.5-2.0.
3. The process of claim 1 wherein the reaction temperature is from 0 ℃ to 120 ℃.
4. The method according to claim 1, wherein the reaction time is 2 to 48 hours.
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