CN109020877B - Alkyl modified aryl pyridine compound and preparation method thereof - Google Patents

Alkyl modified aryl pyridine compound and preparation method thereof Download PDF

Info

Publication number
CN109020877B
CN109020877B CN201710431886.9A CN201710431886A CN109020877B CN 109020877 B CN109020877 B CN 109020877B CN 201710431886 A CN201710431886 A CN 201710431886A CN 109020877 B CN109020877 B CN 109020877B
Authority
CN
China
Prior art keywords
pyridine
nmr
cdcl
aryl
carbon atom
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201710431886.9A
Other languages
Chinese (zh)
Other versions
CN109020877A (en
Inventor
张扬会
王晓玲
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tongji University
Original Assignee
Tongji University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tongji University filed Critical Tongji University
Priority to CN201710431886.9A priority Critical patent/CN109020877B/en
Publication of CN109020877A publication Critical patent/CN109020877A/en
Application granted granted Critical
Publication of CN109020877B publication Critical patent/CN109020877B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C07D213/16—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 containing only one pyridine ring
    • 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
    • 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
    • C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/26—Radicals substituted by halogen atoms or nitro radicals
    • 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
    • C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • 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
    • C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57—Nitriles
    • 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
    • C07D401/10—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 linked by a carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

The invention relates to an alkyl modified aryl pyridine compound and a preparation method thereof, wherein the aryl pyridine compound has the following structural formula:
Figure DDA0001317543230000011
wherein R is a substituent on a benzene ring, is H or at least one of substituents containing halogen, aryl, methyl or methoxy, and R is1Selected from the group consisting of aryl, cyano, and methylOne of an alkane of oxy, n-butyl, isopropyl or phthalimido; the aryl pyridine compound is synthesized by the following method: taking divalent palladium salt as a catalyst, mixing aryl pyridine, halogenated aromatic hydrocarbon, a ligand compound, an oxidant and the catalyst, dissolving the mixture in an organic solvent, and reacting to obtain the alkyl modified aryl pyridine compound. Compared with the prior art, the method has the advantages of mild conditions, good yield, simple operation and wide substrate application range.

Description

Alkyl modified aryl pyridine compound and preparation method thereof
Technical Field
The invention relates to the field of organic synthesis, in particular to an alkyl modified aryl pyridine compound and a preparation method thereof.
Background
Compounds containing alkyl structures are important components of many biological medicines, natural products, and chemical materials. The main methods for constructing carbon-carbon bonds in traditional chemistry include nucleophilic addition, nucleophilic substitution, Friedel-Crafts reaction, and the like. The origin of modern coupling reactions dates back to the last 70 s, and the great impact of such reactions on organic synthesis technology and the development of such reactions over the last two decades have gained widespread acceptance. However, on the one hand, the reaction substrates such as organometallic reagents and organic halides used in such reactions are mostly expensive or require multiple steps to be synthesized, which increases the reaction cost. On the other hand, the reagent can generate self-coupling side reaction in the reaction process, and simultaneously, chemical waste can be generated due to a large amount of leaving groups after the reaction is finished, so that the utilization rate of raw materials is low, and the environment is polluted.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide an alkyl modified aryl pyridine compound and a preparation method thereof.
The purpose of the invention can be realized by the following technical scheme:
an alkyl modified aryl pyridine compound, wherein the structural formula of the aryl pyridine compound is as follows:
Figure BDA0001317543220000011
wherein R is a substituent on a benzene ring, is H or one of substituents containing halogen, aryl, methyl or methoxy, and R is1Is selected from one of the alkanes containing aryl, cyano, methoxy, n-butyl, isopropyl or phthalimido.
As a preferred embodiment, R is selected from the group consisting of H, 4-Me, 4-Cl, 4-Ph, 4-OMe, 4-CF3、4-C(CH3)3、4-COCH3One of 3-OMe, 3-Me, 3,5-diMe, 3,5-diOMe, 3,4-diOMe and 2-Benzo, wherein "2-" represents a carbon atom adjacent to a carbon atom bonded to a pyridine ring on a benzene ring, "3-" represents a carbon atom meta to the carbon atom bonded to the pyridine ring on the benzene ring, "4-" represents a carbon atom para to the carbon atom bonded to the pyridine ring on the benzene ring, and "5-" represents a carbon atom meta to the other side of the carbon atom bonded to the pyridine ring on the benzene ring in the case that a substituent is provided in the "3-" position.
A preparation method of an alkyl modified aryl pyridine compound comprises the steps of taking a divalent palladium salt as a catalyst, mixing aryl pyridine, halogenated aromatic hydrocarbon, a ligand compound, an oxidant and the catalyst, dissolving the mixture in an organic solvent, and reacting to obtain the alkyl modified aryl pyridine compound.
As a preferred embodiment, the molar ratio of aryl pyridine, alkyl iodide, ligand compound, oxidant, catalyst is 1: (4-8): (0.4-1): (2-4): (0.01-0.1);
the reaction process conditions are as follows: reacting for 4-8h at 40-80 ℃. More preferred process conditions are: the temperature is 60 ℃, and the reaction time is 6 h.
As a preferred embodiment, the arylpyrazoles have the following structure:
Figure BDA0001317543220000021
as a preferred embodiment, the iodoalkane has a structure of R1-I。
In a preferred embodiment, the ligand compound is selected from one of amino acids, pyridines or phosphoric acid compounds. More preferably, the ligand compound is dibenzyl phosphate, and the structural formula of the ligand compound is as follows:
Figure BDA0001317543220000022
in a preferred embodiment, the oxidizing agent is at least one of silver carbonate, silver oxide or silver fluoride.
As a preferred embodiment, the catalyst is Pd (OAc)2、Pd(TFA)2、PdCl2Or Pd (MeCN) Cl2At least one of (1).
As a preferred embodiment, the organic solvent is a reducing solvent selected from at least one of dichloroethane, 2-methyl-2-butanol, trifluoroacetic acid, 1, 4-dioxane, tetrahydrofuran, toluene, dimethyl sulfoxide, acetonitrile, methanol, n-propanol, isopropanol, n-butanol, or t-pentanol.
The alkyl modified aryl pyridine compound takes aryl pyridine arene and alkyl iodide as raw materials. In the presence of an organic solvent, with Pd (OAc)2Under the action of ligand, the compound is prepared by coupling reaction under the conditions of oxidant and reducing solvent, and the reaction equation is as follows:
Figure BDA0001317543220000031
the product alkyl modified aryl pyridine compound obtained by the method can be separated by thin layer chromatography, column chromatography or reduced pressure distillation, for example, the thin layer chromatography and the column chromatography are used, and the developing solvent is a mixed solvent of a nonpolar solvent and a polar solvent. The recommended solvent can be mixed solvents of petroleum ether-dichloromethane, petroleum ether-ethyl acetate, petroleum ether-diethyl ether and the like, and the volume ratios of the recommended solvents can be respectively as follows: nonpolar 5: 1. for example: petroleum ether/ethyl acetate 5/1.
The function of the additive (namely the ligand compound) of the method is very critical, and when the additive is not added, the reaction effect is very poor, so that the additive has certain influence on the formation of a key intermediate in the reaction process, and the additive can stabilize the reaction intermediate so as to promote the generation of a product. The oxidizing agent functions to oxidize divalent palladium to tetravalent palladium because the reaction proceeds through the oxidative addition of a divalent palladium compound to a haloalkane to produce a tetravalent palladium compound. The addition of the oxidant can promote the oxidation of bivalent palladium into tetravalent palladium so as to improve the catalytic efficiency. Meanwhile, silver ions in the oxidant can play a role in capturing halogen in halogenated alkane. In addition, the method has the greatest advantages that a five-membered ring target intermediate formed by activating a carbon-hydrogen bond is the key of the reaction, a side reaction for eliminating beta hydrogen of halogenated alkane is avoided, and a process with very high atom economy is realized based on the principle of C-H bond activation functionalization reaction. The reaction substrate only needs to leave one hydrogen atom, which greatly reduces the generation of reaction waste, and the reaction can be efficiently realized in an air environment under mild conditions.
Compared with the prior art, the invention has the following advantages:
(1) the method is suitable for different types of aryl pyridine and iodoalkane, and has the advantages of mild reaction conditions and simple and convenient operation.
(2) Based on the process of C-H bond activation functionalization reaction, only one hydrogen atom is left in a reaction substrate, so that the generation of chemical waste is greatly reduced, and the method is a synthetic technology of the aryl pyridine compound with very high atom economy.
Detailed Description
The present invention will be described in detail with reference to specific examples.
The reagents used in the following examples are all commercially available products or prepared by a method conventional in the art unless otherwise specified.
Example 1
Palladium-catalyzed reaction of arylpyridines with butyl iodide
The palladium-catalyzed reaction of aryl pyridine and iodobutane to synthesize the alkyl-substituted aryl pyridine aromatic compound comprises the following steps: to a 35ml Schlenk reaction tube were added, in order, a stirrer, 0.45mg of Pd (OAc)2(10 mol%), the corresponding arylpyridine (0.2mmol), 91.0uL n-butyl iodide (0.8mmol), 44.5mg (BnO)2PO2H(80mol％)，165.4mgAg2CO3(3.0equiv) and 1.0mL of t-Amyloh: CH3CN (9:1), then sealing the reaction tube by a matched polytetrafluoroethylene plug, and placing the reaction tube in a magnetic stirrer at 60 ℃ for reaction for 12 hours. When the reaction is finished, the reaction tube is removed from the heating device and cooled to room temperature,diluting the reaction solution with ethyl acetate, performing suction filtration through diatomite, washing for several times with ethyl acetate to obtain filtrate, concentrating the filtrate with a rotary evaporator, purifying and separating the obtained crude product with a silica gel plate to obtain a corresponding butyl compound, weighing to determine the yield, and performing qualitative detection by using NMR and HRMS.
Figure BDA0001317543220000041
The following 13 experiments can be divided according to the difference of R groups in aryl pyridine, and the following table 1 specifically shows.
TABLE 1
Figure BDA0001317543220000042
Figure BDA0001317543220000051
Wherein, (BnO)2PO2H is dibenzyl phosphate.
The characterization data of the products of each experimental group by NMR and HRMS are as follows:
experiment 1-1:
and (3) a product A: 2- (2-butylphenyl) pyridine
Figure BDA0001317543220000052
1H NMR(400MHz,CDCl3)8.73(d,J＝3.5Hz,1H),7.79(ddd,J＝7.7,7.7,1.6Hz,1H),7.43(d,J＝7.8Hz,1H),7.40–7.33(m,3H),7.33–7.26(m,2H),1.48(t,J＝7.9Hz,2H),1.55–1.39(m,2H),1.30–1.21(m,2H),0.83(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)160.35,149.12,140.75,140.37,136.09,129.74,129.72,128.28,125.73,124.16,121.63,33.49,32.61,22.51,13.83.HRMS(ESI-TOF)m/z:calcd for C15H17NNa+:234.1253(M+Na)+,found:234.1242.
And (3) a product B: 2- (2,6-dibutylphenyl) pyridine
Figure BDA0001317543220000053
Colorless liquid, 11% yield.
1H NMR(400MHz,CDCl3)8.75(d,J＝4.0Hz,1H),7.78(ddd,J＝7.7,7.7,1.8Hz,1H),7.34–7.26(m,2H),7.16(d,J＝7.6Hz,2H),2.34(t,J＝8.8Hz,4H),1.53–1.37(m,4H),1.24–1.14(m,4H),0.78(t,J＝7.3Hz,6H).13C NMR(101MHz,CDCl3)159.68,149.27,140.71,139.87,135.75,127.93,126.52,125.05,121.61,33.32,33.20,22.56,13.79.HRMS(ESI-TOF)m/z:calcd for C19H25NNa+:290.1879(M+Na)+,found:290.1881.
Experiments 1-2:
and (3) a product A: 2- (2-butyl-4-methylphenyl) pyridine
Figure BDA0001317543220000061
Colorless liquid, 55% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.8Hz,1H),7.76(ddd,J＝7.7,7.7,1.8Hz,1H),7.41(d,J＝7.8Hz,1H),7.30–7.23(m,2H),7.16(s,1H),7.12(d,J＝7.7Hz,1H),2.73(t,J＝7.9Hz,2H),2.42(s,3H),1.56–1.42(m,2H),1.33–1.24(m,2H),0.83(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)160.40,149.09,140.61,137.94,137.56,136.03,130.47,129.74,126.50,124.18,121.42,33.61,32.60,22.58,21.29,13.86.HRMS(ESI-TOF)m/z:calcd for C16H19NNa+:248.1410(M+Na)+,found:248.1404.
And (3) a product B: 2- (2,6-dibutyl-4-methylphenyl) pyridine
Figure BDA0001317543220000062
Colorless liquid, 14% yield.
1H NMR(400MHz,CDCl3)8.74(d,J＝6.8Hz,1H),7.76(ddd,J＝7.7,7.7,1.8Hz,1H),7.32–7.24(m,2H),6.98(s,2H),2.39(s,3H),2.31(t,J＝8.0Hz,4H),1.51–1.33(m,4H),1.27–1.14(m,4H),0.78(t,J＝7.3Hz,6H).13C NMR(101MHz,CDCl3)159.85,149.25,140.62,137.34,137.16,135.66,127.29,125.26,121.46,33.41,33.17,22.62,21.33,13.80.HRMS(ESI-TOF)m/z:calcd for C20H27NNa+:304.2036(M+Na)+,found:304.2034.
Experiments 1-3:
and (3) a product A: 2- (4- (tert-butyl) -2-butylphenyl) pyridine
Figure BDA0001317543220000063
Colorless liquid, 61% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.2Hz,1H),7.77(ddd,J＝7.7,7.7,1.7Hz,1H),7.44(d,J＝7.8Hz,1H),7.35(s,1H),7.34(s,2H),7.27(dd,J＝7.0,5.4Hz,1H),2.76(t,J＝7.9Hz,2H),1.54–1.44(m,2H),1.40(s,9H),1.31–1.24(m,2H),0.84(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)160.41,151.14,149.12,140.24,137.51,136.02,129.50,126.81,124.07,122.79,121.42,34.60,33.76,33.03,31.41,22.64,13.90.HRMS(ESI-TOF)m/z:calcd for C19H25NNa+:290.1879(M+Na)+,found:290.1887.
And (3) a product B: 2- (4- (tert-butyl) -2, 6-dibutylphenyl) pyridine
2-(4-(tert-butyl)-2,6-dibutylphenyl)pyridine
Figure BDA0001317543220000071
Colorless liquid, 12% yield.
1H NMR(400MHz,CDCl3)8.73(d,J＝4.8Hz,1H),7.77(ddd,J＝7.7,7.7,1.7Hz,1H),7.34–7.31(m,1H),7.30–7.25(m,1H),7.16(s,2H),2.34(t,J＝7.9Hz,4H),1.38(s,9H),1.36–1.28(m,4H),1.23–1.15(m,4H),0.78(t,J＝7.3Hz,6H).13C NMR(101MHz,CDCl3)159.91,150.51,149.19,140.16,137.02,135.65,125.12,123.64,121.45,34.51,33.59,33.56,31.44,22.63,13.83.HRMS(ESI-TOF)m/z:calcdfor C23H33NNa+:346.2505(M+Na)+,found:346.2519.
Experiments 1-4:
and (3) a product A: 2- (3-butyl- [1, 1' -diphenyl ] -4-yl) pyridine
2-(3-butyl-[1,1'-biphenyl]-4-yl)pyridine
Figure BDA0001317543220000072
White solid, 52% yield.
1H NMR(400MHz,CDCl3)8.76(d,J＝4.7Hz,1H),7.81(ddd,J＝7.7,7.7,1.7Hz,1H),7.70(d,J＝7.8Hz,2H),7.59(s,1H),7.56(d,J＝8.0Hz,1H),7.50(dd,J＝15.6,7.7Hz,4H),7.41(t,J＝7.3Hz,1H),7.34–7.28(m,1H),2.84(t,J＝7.8Hz,2H),1.60–1.50(m,2H),1.36–1.25(m,2H),0.86(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)160.05,149.23,141.24,141.13,141.07,139.34,136.16,130.32,128.78,128.64,127.35,127.23,124.58,124.16,121.68,33.60,32.84,22.59,13.88.HRMS(ESI-TOF)m/z:calcd for C21H21NNa+:310.1566(M+Na)+,found:310.1560.
And (3) a product B: 2- (3, 5-dibutyl- [1, 1' -diphenyl ] -4-yl) pyridine
2-(3,5-dibutyl-[1,1'-biphenyl]-4-yl)pyridine
Figure BDA0001317543220000081
White solid, 17% yield.
1H NMR(400MHz,CDCl3)8.78(d,J＝4.7Hz,1H),7.88–7.76(m,1H),7.68(d,J＝7.5Hz,2H),7.50(t,J＝7.6Hz,2H),7.43–7.31(m,5H),2.42(t,J＝7.7Hz,4H),1.54–1.42(m,4H),1.28–1.17(m,4H),0.80(t,J＝7.3Hz,6H).13C NMR(101MHz,CDCl3)159.52,149.39,141.52,141.25,140.77,139.00,135.80,128.69,127.25,127.15,125.52,125.13,121.69,33.39,22.62,13.82.HRMS(ESI-TOF)m/z:calcd for C25H29NNa+:366.2192(M+Na)+,found:366.2196.
Experiments 1-5:
and (3) a product A: 2- (2-butyl-4-chlorophenyl) pyridine
Figure BDA0001317543220000082
Colorless liquid, 40% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.7Hz,1H),7.78(ddd,J＝7.7,7.7,1.7Hz,1H),7.39(d,J＝7.8Hz,1H),7.33(d,J＝2.0Hz,1H),7.32–7.24(m,3H),2.72(t,J＝7.9Hz,2H),1.53–1.41(m,2H),1.29–1.20(m,2H),0.82(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)159.21,149.29,142.83,138.81,136.28,134.04,131.13,129.61,125.89,124.11,121.93,33.21,32.53,22.45,13.81.HRMS(ESI-TOF)m/z:calcd for C15H16ClNNa+:268.0863(M+Na)+,found:268.0867.
And (3) a product B: 2- (2,6-dibutyl-4-chlorophenyl) pyridine
Figure BDA0001317543220000091
Colorless liquid, 9% yield.
1H NMR(400MHz,CDCl3)8.75(d,J＝4.4Hz,1H),7.79(ddd,J＝7.7,7.7,1.6Hz,1H),7.35–7.31(m,1H),7.26(d,J＝7.7Hz,1H),7.15(s,2H),2.30(t,J＝8.9Hz,4H),1.49–1.33(m,4H),1.24–1.11(m,4H),0.78(t,J＝7.3Hz,6H).13C NMR(101MHz,CDCl3)158.64,149.49,142.81,138.39,135.94,133.45,126.40,125.07,121.91,33.05,33.00,22.47,13.75.HRMS(ESI-TOF)m/z:calcd for C19H24ClNNa+:324.1489(M+Na)+,found:324.1492.
Experiments 1-6:
and (3) a product A: 1- (3-butyl-4- (pyridin-2-yl) acetyl-1-one
1-(3-butyl-4-(pyridin-2-yl)phenyl)ethan-1-one
Figure BDA0001317543220000092
Colorless solid, 40% yield.
1H NMR(400MHz,CDCl3)8.75(d,J＝4.1Hz,1H),7.95(d,J＝1.4Hz,1H),7.88(dd,J＝7.9,1.7Hz,1H),7.82(ddd,J＝7.7,7.7,1.8Hz,1H),7.48(d,J＝7.9Hz,1H),7.43(d,J＝7.8Hz,1H),7.34(ddd,J＝7.5,4.9,1.0Hz,1H),2.79(t,J＝8.2Hz,2H),2.68(s,3H),1.56–1.43(m,2H),1.32–1.19(m,2H),0.83(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)198.21,159.21,149.34,144.83,141.44,136.81,136.32,130.12,129.67,125.86,124.03,122.22,33.36,32.65,26.79,22.49,13.78.HRMS(ESI-TOF)m/z:calcd for C17H19NNaO+:276.1359(M+Na)+,found:276.1359.
Experiments 1-7:
and (3) a product A: 2- (2-butyl-4- (trifluoromethyl) phenylpyridine
2-(2-butyl-4-(trifluoromethyl)phenyl)pyridine
Figure BDA0001317543220000093
White solid, 32% yield.
1H NMR(400MHz,CDCl3)8.75(d,J＝4.3Hz,1H),7.82(ddd,J＝7.7,7.7,1.8Hz,1H),7.60(s,1H),7.56(d,J＝8.1Hz,1H),7.49(d,J＝8.0Hz,1H),7.42(d,J＝7.8Hz,1H),7.38–7.32(m,1H),2.78(t,J＝7.9Hz,2H),1.55–1.45(m,2H),1.32–1.23(m,2H),0.83(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)158.97,149.37,143.67,141.80,136.35,130.36(q,J＝32.0Hz),130.17,126.47(q,J＝3.7Hz),124.26(q,J＝272.3Hz),124.01,122.55(q,J＝3.8Hz),122.25,33.20,32.61,22.45,13.73.HRMS(ESI-TOF)m/z:calcd for C16H16F3NNa+:302.1127(M+Na)+,found:320.1153.
Experiments 1-8:
and (3) a product A: 2- (2-butyl-5-methylphenyl) pyridine
Figure BDA0001317543220000101
Colorless liquid, 62% yield.
1H NMR(400MHz,CDCl3)8.73(d,J＝4.5Hz,1H),7.77(ddd,J＝7.7,7.7,1.4Hz,1H),7.41(t,J＝7.5Hz,1H),7.32–7.26(m,1H),7.26–7.16(m,3H),2.70(t,J＝8.29Hz,2H),2.40(s,3H),1.53–1.38(m,2H),1.32–1.19(m,2H),0.82(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)160.39,149.20,140.20,137.59,136.00,135.18,130.42,129.68,128.95,124.14,121.56,33.65,32.19,22.52,20.98,13.88.HRMS(ESI-TOF)m/z:calcd for C16H19NNa+:248.1410(M+Na)+,found:248.1404.
And (3) a product B: 2- (2,6-dibutyl-3-methylphenyl) pyridine
Figure BDA0001317543220000102
Colorless liquid, 7% yield.
1H NMR(400MHz,CDCl3)8.74(d,J＝3.6Hz,1H),7.78(ddd,J＝7.7,7.7,1.6Hz,1H),7.34–7.26(m,2H),7.17(d,J＝7.8Hz,1H),7.06(d,J＝7.8Hz,1H),2.37(s,3H),2.34–2.19(m,4H),1.50–1.33(m,4H),1.24–1.08(m,4H),0.82–0.69(m,6H).13C NMR(101MHz,CDCl3)160.27,149.19,140.21,139.06,138.38,135.63,133.49,130.04,126.31,125.04,121.53,33.37,33.10,31.98,30.23,23.07,22.59,19.51,13.83,13.61.HRMS(ESI-TOF)m/z:calcd for C16H19NNa+:304.2046(M+Na)+,found:304.2046.
Experiments 1-9:
product A-1: 2- (2-butyl-5-methoxyphenyl) pyridine
Figure BDA0001317543220000111
White solid, 60% yield.
1H NMR(400MHz,CDCl3)8.73(d,J＝4.1Hz,1H),7.78(ddd,J＝7.7,7.7,1.7Hz,1H),7.42(d,J＝7.8Hz,1H),7.32–7.21(m,2H),6.93(dd,J＝5.4,2.7Hz,2H),3.85(s,3H),2.66(t,J＝7.9Hz,2H),1.50–1.37(m,2H),1.30–1.15(m,2H),0.81(t,J＝7.3Hz,3H).13CNMR(101MHz,CDCl3)160.16,157.47,149.19,141.23,136.09,132.87,130.78,124.09,121.73,114.71,114.36,55.38,33.72,31.78,22.44,13.86.HRMS(ESI-TOF)m/z:calcd forC16H19NNaO+:264.1359(M+Na)+,found:264.1364.
And (3) a product B: 2- (2, 6-dibutyl-3-methoxyphenyl) pyridine
2-(2,6-dibutyl-3-methoxyphenyl)pyridine
Figure BDA0001317543220000112
White solid, 8% yield.
1H NMR(400MHz,CDCl3)8.74(d,J＝4.6Hz,1H),7.78(ddd,J＝7.7,7.7,1.6Hz,1H),7.31(s,1H),7.28(s,1H),7.11(d,J＝8.4Hz,1H),6.89(d,J＝8.4Hz,1H),3.87(s,3H),2.37–2.19(m,4H),1.49–1.28(m,4H),1.23–1.09(m,4H),0.81–0.62(m,6H).13C NMR(101MHz,CDCl3)159.65,155.67,149.19,141.08,135.64,132.77,129.67,126.90,124.95,121.60,110.26,55.64,33.50,32.62,32.07,27.16,22.94,22.53,13.83,13.75.HRMS(ESI-TOF)m/z:calcd for C20H27NNaO+:320.1985(M+Na)+,found:320.1996.
Product A-2: 2- (2-butyl-3-methoxyphenyl) pyridine
Figure BDA0001317543220000113
White solid, 6% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.3Hz,1H),7.78(ddd,J＝7.7,7.7,1.6Hz,1H),7.41(d,J＝7.8Hz,1H),7.27(dd,J＝9.2,6.8Hz,2H),6.97(dd,J＝10.2,8.2Hz,2H),3.89(d,J＝14.3Hz,3H),2.75–2.59(m,2H),1.51–1.40(m,2H),1.27–1.16(m,2H),0.80(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)160.34,157.89,149.07,141.85,135.94,129.82,126.28,124.21,122.00,121.64,110.33,55.68,32.16,26.29,22.84,13.82.HRMS(ESI-TOF)m/z:calcd for C16H19NNaO+:264.1359(M+Na)+,found:264.1365.
Experiments 1-10:
and (3) a product A: 2- (3-Butylnaphthalen-2-yl) pyridine 2- (3-butylnaphtalen-2-yl) pyridine
Figure BDA0001317543220000121
White solid, 41% yield.
1H NMR(400MHz,CDCl3)8.78(d,J＝4.5Hz,1H),7.93–7.76(m,5H),7.59–7.45(m,3H),7.34(dd,J＝6.9,5.4Hz,1H),2.94(t,J＝7.9Hz,2H),1.56–1.42(m,2H),1.35–1.22(m,2H),0.84(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)160.32,149.12,139.30,138.79,136.30,133.40,131.79,129.10,127.95,127.87,127.16,126.26,125.47,124.34,121.80,33.19,33.04,22.53,13.90.HRMS(ESI-TOF)m/z:calcd for C19H19NNa+:284.1410(M+Na)+,found:284.1420.
And (3) a product B: 2- (1, 3-Dibutylnaphthol-2-yl) pyridine 2- (1, 3-dibutylnaphtalen-2-yl) pyridine
Figure BDA0001317543220000122
White solid, 10% yield.
1H NMR(400MHz,CDCl3)8.80(d,J＝3.6Hz,1H),8.06(dd,J＝13.9,8.1Hz,1H),7.92–7.77(m,2H),7.65(s,1H),7.59–7.48(m,2H),7.35(d,J＝7.7Hz,2H),2.76(t,J＝7.9Hz,2H),2.50–2.40(m,2H),1.72–1.60(m,1H),1.59–1.41(m,3H),1.36–1.18(m,4H).0.81(t,J＝7.3Hz,6H).13C NMR(101MHz,CDCl3)160.19,149.35,138.55,138.45,136.85,135.82,133.75,130.43,128.19,125.57,125.24,125.17,124.43,121.78,121.35,33.71,33.18,32.89,29.65,23.18,22.61,13.86,13.73.HRMS(ESI-TOF)m/z:calcd for C23H27NNa+:340.2036(M+Na)+,found:340.2047.
Experiments 1-11:
and (3) a product A: 2- (2-butyl-3, 4-dimethoxyphenyl) pyridine
2-(2-butyl-3,4-dimethoxyphenyl)pyridine
Figure BDA0001317543220000131
White solid, 62% yield.
1H NMR(400MHz,CDCl3)8.70(d,J＝4.6Hz,1H),7.77(t,J＝7.7Hz,1H),7.39(d,J＝7.6Hz,1H),7.30–7.24(m,1H),7.10(d,J＝8.4Hz,1H),6.88(d,J＝8.4Hz,1H),3.94(s,3H),3.90(s,3H),2.77(t,J＝8.1Hz,2H),1.38(dd,J＝15.3,8.0Hz,2H),1.27–1.16(m,2H),0.78(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)160.18,152.74,149.00,147.36,136.09,135.48,125.48,124.21,121.43,109.55,100.22,60.76,55.72,32.89,26.39,22.81,13.75.HRMS(ESI-TOF)m/z:calcd for C17H21NNaO2 +:294.1465(M+Na)+,found:294.1466.
And (3) a product B: 2- (2,6-dibutyl-3, 4-dimethoxyphenyl) pyridine
2-(2,6-dibutyl-3,4-dimethoxyphenyl)pyridine
Figure BDA0001317543220000132
White solid, 8% yield.
1H NMR(400MHz,CDCl3)8.73(d,J＝3.8Hz,1H),7.77(t,J＝7.5Hz,1H),7.31–7.24(m,2H),6.72(s,1H),3.93(s,3H),3.87(s,3H),2.43–2.32(m,2H),2.31–2.23(m,2H),1.51–1.33(m,4H),1.24–1.10(m,4H),0.78(t,J＝7.3Hz,3H),0.72(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)159.41,152.11,149.16,145.05,136.61,135.75,135.09,133.23,125.53,121.59,110.61,60.74,55.70,33.52,33.33,32.82,27.32,22.92,22.60,13.85,13.58.HRMS(ESI-TOF)m/z:calcd for C21H29NNaO2 +:350.2091(M+Na)+,found:350.2094.
Experiments 1-12:
and (3) a product A: 2- (2-butyl-3, 5-dimethoxyphenyl) pyridine
2-(2-butyl-3,5-dimethoxyphenyl)pyridine
Figure BDA0001317543220000141
White solid, 42% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.1Hz,1H),7.77(t,J＝7.7Hz,1H),7.38(t,J＝14.0Hz,1H),7.29(d,J＝9.9Hz,1H),6.53(d,J＝10.3Hz,2H),3.88(s,3H),3.85(s,3H),2.56(t,J＝7.9Hz 2H),1.50–1.35(m,2H),1.26–1.13(m,2H),0.79(t,J＝7.3Hz,3H).13CNMR(101MHz,CDCl3)160.40,158.90,158.17,149.12,142.05,135.89,124.15,122.42,121.72,105.36,98.87,55.65,55.42,32.42,25.81,22.68,13.81.HRMS(ESI-TOF)m/z:calcd for C17H21NNaO2 +:294.1465(M+Na)+,found:294.1469.
And (3) a product B: 2- (2,6-dibutyl-3, 5-dimethoxyphenyl) pyridine
2-(2,6-dibutyl-3,5-dimethoxyphenyl)pyridine
Figure BDA0001317543220000142
White solid, 14% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.4Hz,1H),7.76(t,J＝7.6Hz,1H),7.28(d,J＝7.6Hz,2H),6.56(s,1H),3.89(s,6H),2.34–2.12(m,4H),1.46–1.32(m,2H),1.31–1.22(m,2H),1.19–1.08(m,4H),0.73(t,J＝7.3Hz,6H).13C NMR(101MHz,CDCl3)159.69,156.26,149.04,141.90,135.47,124.89,121.85,121.54,95.72,55.85,32.39,26.64,22.86,13.72.HRMS(ESI-TOF)m/z:calcd for C21H29NNaO2 +:350.2091(M+Na)+,found:350.2098.
Experiments 1-13:
and (3) a product A: 2- (2-dibutyl-3, 5-dimethylphenyl) pyridine
2-(2-butyl-3,5-dimethylphenyl)pyridine
Figure BDA0001317543220000143
Colorless liquid, 70% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.7Hz,1H),7.77(ddd,J＝7.7,7.7,1.7Hz,1H),7.40(d,J＝7.8Hz,1H),7.28(ddd,J＝7.4,5.4,2.5Hz,1H),7.08(s,1H),7.01(s,1H),2.65(t,J＝7.9Hz,2H),2.43(s,3H),2.36(s,3H),1.47–1.33(m,2H),1.28–1.16(m,2H),0.80(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)161.24,148.90,140.91,136.58,136.12,135.96,134.73,131.29,128.24,124.21,121.48,32.40,28.90,22.89,20.85,19.78,13.72.HRMS(ESI-TOF)m/z:calcd for C17H21NNa+:262.1566(M+Na)+,found:262.1564.
And (3) a product B: 2- (2,6-dibutyl-3, 5-dimethylphenyl) pyridine
2-(2,6-dibutyl-3,5-dimethylphenyl)pyridine
Figure BDA0001317543220000151
Colorless liquid, 11% yield.
1H NMR(400MHz,CDCl3)8.73(d,J＝4.2Hz,1H),7.76(ddd,J＝7.7,7.7,1.8Hz,1H),7.33–7.28(m,2H),7.04(s,1H),2.33(s,6H),2.27–2.16(m,4H),1.47–1.34(m,2H),1.34–1.21(m,2H),1.19–1.08(m,4H),0.73(t,J＝7.3Hz,6H).13C NMR(101MHz,CDCl3)160.85,149.05,140.60,136.76,135.46,133.28,132.25,125.04,121.43,32.10,30.15,23.04,19.29,13.58.HRMS(ESI-TOF)m/z:calcd for C21H29NNa+:318.2192(M+Na)+,found:318.2205.
Example 2
Palladium catalyzed reaction of 2-phenylpyridine with an alkyl iodide
To a 35ml Schlenk reaction tube were added, in order, a stirrer, 0.45mg of Pd (OAc)2(10 mol%), corresponding 28.6uL 2-phenylpyridine (0.2mmol), iodoalkane (0.8mmol), 44.5mg (BnO)2PO2H(80mol％)，165.4mgAg2CO3(3.0equiv) and 1.0mL of t-Amyloh: CH3CN (9:1), then sealing the reaction tube by a matched polytetrafluoroethylene plug, and placing the reaction tube in a magnetic stirrer at 60 ℃ for reaction for 12 hours. And (3) moving the reaction tube away from the heating device when the reaction is finished, cooling to room temperature, diluting the reaction liquid with ethyl acetate, performing suction filtration through diatomite, washing the ethyl acetate for a plurality of times to obtain filtrate, concentrating the filtrate by using a rotary evaporator, purifying and separating the obtained crude product through a silica gel plate to obtain a corresponding butyl compound, weighing to determine the yield, and performing qualitative detection by using NMR and HRMS.
Figure BDA0001317543220000161
According to R in iodoalkane1The differences of the groups can be divided into the following groups of experiments, and the specific characteristics are shown in the following table 2.
TABLE 2
Figure BDA0001317543220000162
Wherein (BnO)2PO2H is dibenzyl phosphate.
The characterization data of the products of each experimental group by NMR and HRMS are as follows:
experiments 2-14:
and (3) a product C: 2- (2-heptylphenyl) pyridine 2- (2-ethylphenyl) pyridine
Figure BDA0001317543220000163
Colorless liquid, 60% yield.
1H NMR(400MHz,CDCl3)8.73(dd,J＝4.8,0.7Hz,1H),7.78(ddd,J＝7.7,7.7,1.6Hz,1H),7.42(d,J＝7.8Hz,1H),7.40–7.34(m,3H),7.30(ddd,J＝7.5,6.7,4.9Hz,2H),2.74(t,J＝7.9Hz,2H),1.56–1.43(m,2H),1.29–1.16(m,8H),0.88(t,J＝7.0Hz,3H).13CNMR(101MHz,CDCl3)160.36,149.12,140.82,140.34,136.10,129.75,129.73,128.30,125.74,124.15,121.63,32.96,31.72,31.30,29.42,28.98,22.66,14.12.HRMS(ESI-TOF)m/z:calcd for C18H23NNa+:276.1723(M+Na)+,found:276.1729.
And (3) a product D: 2- (2,6-diheptylphenyl) pyridine
Figure BDA0001317543220000171
Colorless liquid, 12% yield.
1H NMR(400MHz,CDCl3)8.75(dd,J＝5.9,1.6Hz,1H),7.78(ddd,J＝7.7,7.7,1.8Hz,1H),7.30(d,J＝6.5Hz,3H),7.15(d,J＝7.6Hz,2H),2.41–2.27(m,4H),1.53–1.35(m,4H),1.28–1.22(m,4H),1.16(s,12H),0.87(t,J＝7.1Hz,6H).13C NMR(101MHz,CDCl3)159.69,149.28,140.78,139.83,135.73,127.94,126.51,125.03,121.60,33.57,31.67,31.12,29.50,28.92,22.64,14.10.HRMS(ESI-TOF)m/z:calcd for C25H37NNa+:374.2818(M+Na)+,found:374.2818
Experiments 2-15:
and (3) a product C: 2- (2- (3-phenylpropyl) phenyl) pyridine
Figure BDA0001317543220000172
White solid, 62% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.2Hz,1H),7.75(t,J＝7.7Hz,1H),7.40(t,J＝17.2Hz,5H),7.32–7.25(m,3H),7.25–7.17(m,1H),7.13(d,J＝7.4Hz,2H),2.84(t,J＝7.6Hz,2H),2.59(t,J＝7.5Hz,2H),1.92–1.80(m,2H).13C NMR(101MHz,CDCl3)160.26,149.23,142.31,140.48,140.35,136.19,129.91,128.45,128.28,126.02,125.68,124.10,121.69,35.77,32.87,32.72.HRMS(ESI-TOF)m/z:calcd for C20H19NNa+:296.1410(M+Na)+,found:296.1409.
And (3) a product D: 2- (2, 6-bis (3-phenylpropyl) phenyl) pyridine
2-(2,6-bis(3-phenylpropyl)phenyl)pyridine
Figure BDA0001317543220000173
White solid, 19% yield.
1H NMR(400MHz,CDCl3)8.70(d,J＝4.3Hz,1H),7.75–7.64(m,1H),7.34–7.21(m,7H),7.18(dd,J＝7.3,5.4Hz,4H),7.07(d,J＝7.2Hz,4H),2.50(t,J＝7.6Hz,4H),2.40(t,J＝8.0Hz,4H),1.88–1.67(m,4H).13C NMR(101MHz,CDCl3)159.33,149.35,142.20,140.30,140.04,135.75,128.33,128.17,128.06,126.75,125.55,124.85,121.67,35.75,33.22,32.55.HRMS(ESI-TOF)m/z:calcd for C29H29NNa+:414.2192(M+Na)+,found:414.2192.
Experiments 2-16:
and (3) a product C: 5- (2- (pyridin-2-yl) phenyl) valeronitrile 5- (2- (pyridine-2-yl) phenyl) pentanoyle
Figure BDA0001317543220000181
Colorless liquid, 52% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.7Hz,1H),7.80(t,J＝7.0Hz,1H),7.42(d,J＝7.8Hz,1H),7.37(d,J＝4.9Hz,2H),7.31(dd,J＝11.8,5.9Hz,3H),2.80(t,J＝7.5Hz,2H),2.23(t,J＝6.9Hz,2H),1.73–1.62(m,2H),1.62–1.52(m,2H).13C NMR(101MHz,CDCl3)160.12,149.12,140.36,139.36,136.47,129.95,129.79,128.50,126.25,124.12,121.87,119.70,31.94,30.08,24.98,16.83.HRMS(ESI-TOF)m/z:calcd for C16H16N2Na+:259.1206(M+Na)+,found:259.1202.
Experiments 2-17:
and (3) a product C: 2- (2- (4-methoxybutyl) phenyl) pyridine
Figure BDA0001317543220000182
White solid, 50% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.6Hz,1H),7.78(ddd,J＝7.7,7.7,1.7Hz,1H),7.42(d,J＝7.8Hz,1H),7.39–7.33(m,3H),7.32–7.25(m,2H),3.32–3.26(m,5H),2.77(t,J＝7.2Hz,2H),1.63–1.45(m,4H).13C NMR(101MHz,CDCl3)160.27,149.11,140.33,140.32,136.19,129.79,129.73,128.34,125.88,124.16,121.67,72.54,58.49,32.64,29.35,27.76.HRMS(ESI-TOF)m/z:calcd for C16H19NNaO+:264.1359(M+Na)+,found:264.1361.
Experiments 2-18:
and (3) a product C: 2- (2-isobutylphenyl) pyridine
Figure BDA0001317543220000191
Colorless liquid, 27% yield.
1H NMR(400MHz,CDCl3)8.72(d,J＝4.3Hz,1H),7.78(ddd,J＝7.7,7.7,1.6Hz,1H),7.48–7.22(m,6H),2.68(d,J＝7.2Hz,2H),1.70–1.58(m,1H),0.76(d,J＝6.6Hz,6H).13C NMR(101MHz,CDCl3)160.58,149.08,140.74,139.58,136.09,130.56,129.79,128.03,125.84,124.29,121.57,42.05,29.81,22.43.HRMS(ESI-TOF)m/z:calcd forC15H17NNa+:234.1253(M+Na)+,found:234.1250.
And (3) a product D: 2- (2,6-diisobutylphenyl) pyridine
Figure BDA0001317543220000192
Colorless liquid, 11% yield.
1H NMR(400MHz,CDCl3)8.74(d,J＝4.7Hz,1H),7.77(t,J＝8.1Hz,1H),7.27(d,J＝7.7Hz,3H),7.13(d,J＝7.6Hz,2H),2.35–2.17(m,4H),1.68–1.58(m,2H),0.83–0.68(m,12H).13C NMR(101MHz,CDCl3)159.75,149.14,140.58,139.52,135.59,127.54,127.33,125.50,121.51,42.78,29.41,22.68,22.43.HRMS(ESI-TOF)m/z:calcd for C19H25NNa+:290.1879(M+Na)+,found:290.1880.
Experiments 2-19:
and (3) a product C: 2- (4- (2- (pyridin-2-yl) phenyl) butyl) isoindole-1, 3-dione
2-(4-(2-(pyridin-2-yl)phenyl)butyl)isoindoline-1,3-dione
Figure BDA0001317543220000193
1H NMR(400MHz,CDCl3)8.67(d,J＝4.5Hz,1H),7.92–7.78(m,2H),7.71(dd,J＝7.8,6.1Hz,3H),7.42–7.28(m,5H),7.25–7.19(m,1H),3.61(t,J＝6.9Hz,2H),2.80(t,J＝7.3Hz,2H),1.67–1.57(m,2H),1.57–1.47(m,2H).13C NMR(101MHz,CDCl3)168.35,160.17,149.09,140.29,139.96,136.22,133.86,132.13,129.81,128.38,125.99,124.04,123.14,121.69,37.78,32.53,28.36,28.35.HRMS(ESI-TOF)m/z:calcd for C23H20N2NaO2 +:379.1417(M+Na)+,found:379.1403.
Example 3
Reacting 2-phenylpyridine, iodobutane, dibenzyl phosphate, silver carbonate and Pd (TFA)2Mixing the raw materials according to a molar ratio of 1:4:0.8:3:0.01, dissolving the mixture in a solvent of tertiary amyl alcohol, sealing a reaction tube by using a matched polytetrafluoroethylene plug, and placing the reaction tube in a magnetic stirrer at the temperature of 80 ℃ for reaction for 12 hours. Reaction ofAnd (3) when the reaction is finished, moving the reaction tube away from the heating device, cooling to room temperature, diluting the reaction liquid with ethyl acetate, performing suction filtration through diatomite, washing the reaction liquid with ethyl acetate for a plurality of times, concentrating the obtained filtrate with a rotary evaporator, purifying and separating the obtained crude product through a silica gel plate to obtain a corresponding butyl compound, and weighing to calculate the yield. The final product was:
Figure BDA0001317543220000201
the yields were 76% and 12%, respectively.
Example 4
Mixing 2-phenylpyridine, iodobutane, 2, 6-dimethylpyridine, silver carbonate and PdCl2Mixing the raw materials according to a molar ratio of 1:4:0.2:3:0.01, dissolving the mixture in a solvent of tertiary amyl alcohol, sealing a reaction tube by using a matched polytetrafluoroethylene plug, and placing the reaction tube in a magnetic stirrer at the temperature of 80 ℃ for reaction for 12 hours. And (3) moving the reaction tube away from the heating device when the reaction is finished, cooling to room temperature, diluting the reaction liquid with ethyl acetate, performing suction filtration through diatomite, washing the ethyl acetate for a plurality of times to obtain filtrate, concentrating the filtrate by using a rotary evaporator, purifying and separating the obtained crude product through a silica gel plate to obtain a corresponding butyl compound, and weighing to calculate the yield. The final product was:
Figure BDA0001317543220000202
the yields were 60% and 11%, respectively.
Example 5
Compared with example 3, most of them are the same except that in this example, 2-phenylpyridine, iodobutane, dibenzyl phosphate, silver carbonate and Pd (TFA)2In a molar ratio of 1:6:1:4: 0.1.
Example 6
Compared with example 3, most of them are the same except that in this example, 2-phenylpyridine, iodobutane, dibenzyl phosphate, silver carbonate and Pd (TFA)2In a molar ratio of 1:8:0.4:2: 0.02.
Example 7
Most of the same is true as in example 3, except that in this example, silver carbonate is replaced by silver oxide.
Example 8
Compared to example 4, most of them are the same except that in this example, silver carbonate is changed to silver fluoride.
Example 9
Compared with example 1, most of the components are the same, except that in the example, palladium acetate is changed into PdCl2。
Example 10
Compared with example 1, most of them are the same except that in this example, Pd (OAc)2Instead of Pd (MeCN) Cl2。
Example 11
Compared to example 2, most of them are the same except that in this example, the organic solvent is dichloroethane.
Example 12
Compared to example 2, most of them are the same except that in this example, the organic solvent is changed to trifluoroacetic acid.
Example 13
Compared with example 2, most of them are the same except that in this example, the organic solvent is changed to 1, 4-dioxane.
Example 14
In comparison with example 2, the majority are the same, except that in this example the organic solvent is replaced by tetrahydrofuran.
Example 15
Compared to example 2, most of the same is true except that in this example the organic solvent is toluene instead.
Example 16
Compared with example 2, most of them are the same except that in this example, the organic solvent is dimethyl sulfoxide.
Example 17
Compared to example 2, most of them are the same except that in this example, the organic solvent is changed to acetonitrile.
Example 18
Compared with example 2, most of them are the same except that in this example, the organic solvent is changed to methanol.
Example 19
Compared to example 2, most of them are the same except that in this example, the organic solvent is changed to n-propanol.
Example 20
Compared to example 2, most of them are the same except that in this example, the organic solvent is changed to isopropanol.
Example 21
Compared with example 2, most of the same is true, except that in this example, the organic solvent is n-butanol.
Example 22
Most of the same is true compared to example 2, except that in this example, the reaction conditions are: the temperature is 40 ℃, and the reaction time is 12 h.
Example 23
Most of the same is true compared to example 2, except that in this example, the reaction conditions are: the temperature is 80 ℃, and the reaction time is 4 h.
Example 24
Most of the same is true compared to example 2, except that in this example, the reaction conditions are: the temperature is 60 ℃, and the reaction time is 6 h.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.

Claims (2)

1. A preparation method of an alkyl modified aryl pyridine compound is characterized in that the structural formula of the aryl pyridine compound is as follows:
Figure FDA0002534751890000011
wherein R is1One selected from the group consisting of phthalimido group-containing alkanes; r is selected from H, 4-Me, 4-Cl, 4-Ph, 4-OMe, 4-CF3、4-C(CH3)3、4-COCH3One of 3-OMe, 3-Me, 3,5-diMe, 3,5-diOMe, 3,4-diOMe and 2-benzoyl, wherein "2-" represents a carbon atom adjacent to a carbon atom bonded to a pyridine ring on a benzene ring, "3-" represents a carbon atom meta to the carbon atom bonded to the pyridine ring on the benzene ring, "4-" represents a carbon atom para to the carbon atom bonded to the pyridine ring on the benzene ring, and "5-" represents a carbon atom meta to the other side of the carbon atom bonded to the pyridine ring on the benzene ring with a substituent at the "3-" position;
the preparation method comprises the following steps:
mixing aryl pyridine, iodoalkane, a ligand compound, an oxidant and a catalyst by taking divalent palladium salt as a catalyst, dissolving the mixture in an organic solvent, and reacting to obtain the alkyl modified aryl pyridine compound;
the aryl pyridine has the following structure:
Figure FDA0002534751890000012
the structural formula of the iodoalkane is R1-I; the ligand compound is dibenzyl phosphate; the oxidant is silver carbonate; the catalyst is Pd (OAc)2(ii) a The organic solvent is a mixture of 2-methyl-2-butanol and acetonitrile.
2. The method for preparing alkyl-modified arylpyridines according to claim 1, wherein the molar ratio of arylpyridine to alkyl iodide to ligand compound to oxidant to catalyst is 1: (4-8): (0.4-1): (2-4): (0.01-0.1);
the reaction process conditions are as follows: reacting for 4-8h at 40-80 ℃.
CN201710431886.9A 2017-06-09 2017-06-09 Alkyl modified aryl pyridine compound and preparation method thereof Expired - Fee Related CN109020877B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710431886.9A CN109020877B (en) 2017-06-09 2017-06-09 Alkyl modified aryl pyridine compound and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710431886.9A CN109020877B (en) 2017-06-09 2017-06-09 Alkyl modified aryl pyridine compound and preparation method thereof

Publications (2)

Publication Number Publication Date
CN109020877A CN109020877A (en) 2018-12-18
CN109020877B true CN109020877B (en) 2020-08-18

Family

ID=64628704

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710431886.9A Expired - Fee Related CN109020877B (en) 2017-06-09 2017-06-09 Alkyl modified aryl pyridine compound and preparation method thereof

Country Status (1)

Country Link
CN (1) CN109020877B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114539168B (en) * 2020-11-27 2023-11-17 武汉大学 Method for synthesizing Piraglatin and analogues thereof
CN114574882B (en) * 2022-03-28 2024-02-13 河南师范大学 Method for synthesizing ortho-alkylaryl pyridine compound by electrochemical oxidative dehydrogenation coupling

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105859765A (en) * 2016-04-26 2016-08-17 同济大学 Alkyl-modified pyridylarylsilane compounds and preparation method thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008024953A2 (en) * 2006-08-25 2008-02-28 Brandeis University Transition metal-catalyzed alkylation of c-h bonds with organoboron reagents

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105859765A (en) * 2016-04-26 2016-08-17 同济大学 Alkyl-modified pyridylarylsilane compounds and preparation method thereof

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
Cobalt-Catalyzed C-H Bond Functionalizations with Aryl and Alkyl Chlorides;Benudhar Punji et al.;《Chem. Eur. J.》;20130702;第19卷;第10605-10610页 *
Extrusion of CO from Aryl Ketones: Rhodium(I)-Catalyzed C-C Bond Cleavage Directed by a Pyridine Group;Zhi-Quan Lei et al.;《Angew. Chem. Int. Ed.》;20120206;第51卷;第2690-2694页 *
Long-Range Bonding/Nonbonding Interactions: A Donor−Acceptor Resonance Studied by Dynamic NMR;Renzo Ruzziconi et al.;《Org. Lett.》;20150514;第17卷;第2740-2743页 *
Nickel-catalyzed N-heterocycle-directed cross-coupling of fluorinated arenes with organozinc reagents;Sen-Han Xiao et al.;《Tetrahedron》;20140425;第70卷;第4405-4411页 *
Pd-Catalyzed Monoselective ortho-C−H Alkylation of N‑Quinolyl Benzamides: Evidence for Stereoretentive Coupling of Secondary Alkyl Iodides;Shu-Yu Zhang et al.;《J. Am. Chem. Soc》;20141210;第137卷;第531-539页 *
Regioselectivity-Switchable Hydroarylation of Styrenes;Ke Gao et al.;《J.AM.CHEM.SOC》;20101215;第133卷(第3期);第400-402页 *
Ruthenium-Catalyzed Regioselective Direct Alkylation of Arenes with Unactivated Alkyl Halides through C-H Bond Cleavage;Lutz Ackermann et al.;《Angew. Chem. Int. Ed.》;20090711;第48卷;第6045-6048页 *

Also Published As

Publication number Publication date
CN109020877A (en) 2018-12-18

Similar Documents

Publication Publication Date Title
CN109020877B (en) Alkyl modified aryl pyridine compound and preparation method thereof
Kundu et al. Zwitterionic-type molten salt: a mild and efficient organocatalyst for the synthesis of 3-aminoalkylated indoles via three-component coupling reaction
Otomura et al. Bromine cation initiated vic-diphosphination of styrenes with diphosphines under photoredox catalysis
CN113717396B (en) Copper (I) -based covalent metal organic framework material for catalyzing hydroboration reaction of alkyne and preparation method thereof
Dash et al. C3-symmetric pyridine and bipyridine derivatives: simple preparation by cyclocondensation and 2D self-assembly at a solution–graphite interface
Telvekar et al. Oxidative decarboxylation of 2-aryl carboxylic acids using (diacetoxyiodo) benzene for preparation of aryl aldehydes, ketones, and nitriles
Choudary et al. Highly efficient allylation of aldehydes and three-component synthesis of homoallylamines using bismuth triflate catalyst
Zhao et al. Palladium-catalyzed direct C (sp 3)–H arylation of indole-3-ones with aryl halides: a novel and efficient method for the synthesis of nucleophilic 2-monoarylated indole-3-ones
JP4929468B2 (en) Synthesis method of oligomeric compounds using cross-coupling reaction
Cui et al. Direct Iodosulfonylation of Alkylynones with Sulfonylhydrazides and Iodine Pentoxide Leading to Multisubstituted α, β-Enones
Ng et al. Mild and Efficient Vicinal Dibromination of Olefins Mediated by Aqueous Ammonium Fluoride
da Silva et al. Copper-based 2D-coordination polymer as catalyst for allylation of aldehydes
Biswas et al. Synthesis of 3, 3-Dialkylated Oxindoles by Oxidative Radical 1, 2-Alkylarylation of α, β-Unsaturated Amides
Pena et al. Palladium-catalyzed carbonylative coupling reactions using triorganoindium compounds
CN107629049B (en) Synthesis method of pyridine [2,1-a ] isoindole compound
Chen et al. Palladium-catalyzed intramolecular direct arylation for phosphorus heterocycle synthesis
CN107382910B (en) Difluoromethyl aldehyde hydrazone compound and preparation method thereof
CN110698368A (en) Preparation method of (E) -3-phenyl-3-benzenesulfonyl acrylate compound
Bourne-Branchu et al. Cobalt-Catalyzed Oxidative Homocoupling of Arylzinc Species
Yamamoto et al. Synthesis of functionalized allylsilicone compounds via rhodium-catalyzed conjugate addition of (E)-or (Z)-[3-trimethylsilyl-1-propenyl] boronic acids to enones
JP6011769B2 (en) Polystyrene-supported pyridine bisoxazoline derivative-calcium catalyst
Maerten et al. Direct synthesis of benzoylpyridines from chloropyridines via a palladium-carbene catalyzed carbonylative Suzuki cross-coupling reaction
Wang et al. Copper (I)-Catalyzed Enantioselective 1, 4-Conjugate Hydrophosphination of α, β-Unsaturated Esters
Ouyang et al. Rh (II)-Catalyzed Ring Expansion of Cyclopropyl N-Tosylhydrazones to 1-Substituted Cyclobutenes
Chen et al. An efficient and green oxidation of vicinal diols to aldehydes using polymer-supported (diacetoxyiodo) benzene as the oxidant

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20200818