CN118206466A - N1-Benzyl aryl hydrazine compound, and preparation method and application thereof - Google Patents

N1-Benzyl aryl hydrazine compound, and preparation method and application thereof Download PDF

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CN118206466A
CN118206466A CN202410306683.7A CN202410306683A CN118206466A CN 118206466 A CN118206466 A CN 118206466A CN 202410306683 A CN202410306683 A CN 202410306683A CN 118206466 A CN118206466 A CN 118206466A
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benzyl
compound
aryl hydrazine
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formula
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张振明
舒树丙
余梦
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Jiangxi Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C241/00—Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C241/02—Preparation of hydrazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C243/10—Hydrazines
    • C07C243/22—Hydrazines having nitrogen atoms of hydrazine groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/46—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms
    • C07C323/48—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms to nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

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  • Chemical Kinetics & Catalysis (AREA)
  • Indole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to the field of organic chemistry, in particular to an N 1 -benzyl aryl hydrazine compound, a preparation method and application thereof. The invention uses benzyl alcohol (primary alcohol) and aryl hydrazine as initial raw materials, and constructs a series of N 1 -benzyl aryl hydrazine compounds through the dehydration of DDQ and PPh 3, and is applied to the synthesis of indole compounds. The synthesis method has the advantages that the reaction raw materials are simple and easy to obtain, the reaction conditions are simple, mild, efficient and free of metal residue, the environment-friendly chemical category is met, the indole compound can be efficiently synthesized by the reaction, and the application prospect is very wide.

Description

N 1 -benzyl aryl hydrazine compound and preparation method and application thereof
Technical Field
The invention relates to the field of organic chemistry, in particular to an N 1 -benzyl aryl hydrazine compound, a preparation method and application thereof.
Background
N 1 -substituted aryl hydrazine compounds are not only core frameworks with important bioactive molecules, but also important synthons in organic synthesis, and are widely used for preparing various nitrogen-containing heterocyclic compounds with bioactivity. However, methods for synthesizing such compounds have been limited to date. The traditional synthesis method is nitrous acid diazonium method using aniline, and multiple reactions are designed for such reactions, and highly toxic nitrite is required to be used. Later stages have also developed some nucleophilic substitution reactions to synthesize N 1 -substituted arylhydrazines, however, such reactions require the use of large amounts of strong bases. The recent transition metal catalyzed N 1 -direct functionalization reaction is also a good synthetic strategy, but the participation of transition metals can have problems with metal residues in drug synthesis. Therefore, the development of a simple, efficient and mild method for constructing the N 1 -substituted aryl hydrazine compounds has important research significance and practical application value.
Disclosure of Invention
Based on the above, the invention provides N 1 -benzyl aryl hydrazine compounds, a preparation method and application thereof, and at least solves one problem in the prior art.
In a first aspect, the present invention provides N 1 -benzyl arylhydrazines of formula III:
the compound of the formula III,
Wherein R, R' is independently selected from hydrogen, alkyl, groups containing mono-or poly-substituted electron donating and electron withdrawing effects.
In a second aspect, the invention provides a method for preparing an N 1 -benzyl arylhydrazine compound shown in formula III, which comprises the following steps:
Under the participation of triphenylphosphine (PPh 3) and 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ), enabling benzyl alcohol compounds shown in a formula I and aryl hydrazine compounds shown in a formula II to react in a solvent to obtain N 1 -benzyl aryl hydrazine compounds shown in a formula III;
Formula I,/> A formula II;
Wherein R, R' is independently selected from hydrogen, alkyl, groups containing mono-or poly-substituted electron donating and electron withdrawing effects.
In a third aspect, the invention provides an application of an N 1 -benzyl aryl hydrazine compound shown in a formula III in preparing an indole compound.
Due to the adoption of the technical scheme, the embodiment of the invention has at least the following beneficial effects:
Adopting a dehydration method of organic substances DDQ and PPh 3, under the condition of no metal participation and no alkali participation, using simple and easily obtained benzyl alcohol and aryl hydrazine as raw materials, synthesizing a series of N 1 -benzyl substituted aryl hydrazine compounds simply, efficiently, mildly and without metal residue, and applying the compounds to synthesizing indole compounds; the adopted synthesis method does not need a metal catalyst and alkali, has the advantages of simple and easily obtained raw materials, short reaction route, low production cost, no harsh reaction conditions, high purity of the prepared product, and is a brand new synthesis method which is more economical, more environment-friendly and simpler and milder in reaction conditions, and can be widely applied to synthesizing N-substituted indole compounds.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a compound 3aa in an embodiment of the present invention.
FIG. 2 is a nuclear magnetic resonance carbon spectrum of compound 3aa in the example of the present invention.
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of compound 3ab in the example of the present invention.
FIG. 4 is a nuclear magnetic resonance carbon spectrum of compound 3ab in the example of the present invention.
FIG. 5 is a nuclear magnetic resonance hydrogen spectrum of compound 3ac in the example of the present invention.
FIG. 6 is a nuclear magnetic resonance carbon spectrum of compound 3ac in the example of the present invention.
FIG. 7 is a nuclear magnetic resonance hydrogen spectrum of compound 3ad in the example of the present invention.
FIG. 8 is a nuclear magnetic resonance spectrum of compound 3ad in the example of the present invention.
FIG. 9 is a nuclear magnetic resonance hydrogen spectrum of compound 3ba in the example of the present invention.
FIG. 10 is a nuclear magnetic resonance carbon spectrum of compound 3ba in the example of the present invention.
FIG. 11 is a nuclear magnetic resonance hydrogen spectrum of compound 3ca in the example of the present invention.
FIG. 12 is a nuclear magnetic resonance carbon spectrum of compound 3ca in the example of the present invention.
FIG. 13 is a nuclear magnetic resonance hydrogen spectrum of compound 3da in the example of the present invention.
FIG. 14 is a nuclear magnetic resonance spectrum of compound 3da in the example of the present invention.
FIG. 15 is a nuclear magnetic resonance hydrogen spectrum of compound 3ea in the example of the present invention.
FIG. 16 is a nuclear magnetic resonance carbon spectrum of compound 3ea in the example of the present invention.
FIG. 17 is a nuclear magnetic resonance hydrogen spectrum of the compound 3fa in the example of the present invention.
FIG. 18 is a nuclear magnetic resonance spectrum of 3fa, a compound of the example of the present invention.
FIG. 19 is a nuclear magnetic resonance hydrogen spectrum of Compound 3ga in the example of the present invention.
FIG. 20 is a nuclear magnetic resonance carbon spectrum of 3ga of the compound in the example of the present invention.
FIG. 21 is a nuclear magnetic resonance hydrogen spectrum of compound 3ha in the example of the present invention.
FIG. 22 is a nuclear magnetic resonance carbon spectrum of 3ha of the compound according to the embodiment of the present invention.
FIG. 23 is a nuclear magnetic resonance hydrogen spectrum of compound 4a in the example of the present invention.
FIG. 24 is a nuclear magnetic resonance spectrum of compound 4a according to the embodiment of the present invention.
Detailed Description
The following is a clear and complete description of the conception and technical effects produced thereby to fully illustrate the objects, aspects, and effects of the present invention.
The invention uses benzyl alcohol (primary alcohol) and aryl hydrazine as initial raw materials, and constructs a series of N 1 -benzyl aryl hydrazine compounds through the dehydration of DDQ and PPh 3, and is applied to the synthesis of indole compounds. The synthesis method has the advantages that the reaction raw materials are simple and easy to obtain, the reaction conditions are simple, mild, efficient and free of metal residue, the environment-friendly chemical category is met, the indole compound can be efficiently synthesized by the reaction, and the application prospect is very wide. The invention provides a more environment-friendly path for synthesizing indole drug molecules.
The N 1 -benzyl aryl hydrazine compound has a structure shown in a formula III:
the compound of the formula III,
Wherein R, R' is independently selected from hydrogen, alkyl, groups containing mono-or poly-substituted electron donating and electron withdrawing effects.
In some alternative embodiments, R, R' is independently selected from hydrogen, alkyl of C 1-C18, alkoxy of C 1-C18, phenyl, naphthyl, morpholinyl, halogen atom, thiophenyl, pyrazolyl. Preferably, the R, R' is independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, phenyl, naphthyl, morpholinyl, fluoro, chloro, bromo, iodo, thiophenyl, pyrazolyl.
In some alternative embodiments, the N 1 -benzyl arylhydrazines are one of the compounds of the formula:
。
the preparation method of the N 1 -benzyl aryl hydrazine compound comprises the following steps:
Under the participation of triphenylphosphine (PPh 3) and 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ), enabling benzyl alcohol compounds shown in a formula I and aryl hydrazine compounds shown in a formula II to react in a solvent to obtain N 1 -benzyl aryl hydrazine compounds shown in a formula III;
Wherein R, R' is as defined above.
According to the method, aryl hydrazine compounds and benzyl alcohol compounds are used as starting materials, the N 1 -benzyl substituted aryl hydrazine compounds are constructed by a PPh 3 -DDQ dehydration method through simple thermal reaction, compared with the existing synthetic method of N 1 -benzyl substituted aryl hydrazine compounds, a metal catalyst and alkali are not needed, the raw materials are simple and easy to obtain, the reaction route is short, the experimental operation is convenient, the production cost is low, the reaction condition is not harsh (the operation can be performed under normal pressure), the required equipment is simple), the prepared target product is easy to purify, the yield is good, the product purity is high, and the method is a brand new synthetic method which is more economical, more environment-friendly, and the reaction condition is simpler and milder.
In some alternative embodiments, the aryl hydrazines of formula II are phenylhydrazine, p-tert-butylphenylhydrazine, p-bromophenylhydrazine, 2, 4-dimethylbenzylhydrazine, or p-methylphenylhydrazine. The adopted aryl hydrazine compounds have the advantages of wide sources, low price and rich structure types.
In some alternative embodiments, the benzyl alcohol compound of formula I is p-phenyl benzyl alcohol, p-methoxy benzyl alcohol, p-chlorobenzyl alcohol, p-methyl benzyl alcohol, p-tert-butyl benzyl alcohol, p-bromo benzyl alcohol. The benzyl alcohol is adopted as the raw material, the reaction activity is relatively mild, and the raw material is cheap and easy to obtain.
In some alternative embodiments, the molar ratio of the aryl hydrazine compound of formula II to the benzyl alcohol compound of formula I is (1-3): 1. preferably, the molar ratio of the aryl hydrazine compound shown in the formula II to the benzyl alcohol compound shown in the formula I is 3:1, a step of; the reaction of the raw material benzyl alcohol can be ensured to be complete in the proportion, so that the yield of the target product is improved.
In some alternative embodiments, the solvent is petroleum ether, methylene chloride, acetonitrile, or ethyl acetate.
In some alternative embodiments, the reaction is performed under an oxygen, air, or nitrogen atmosphere.
In some alternative embodiments, the reaction is performed at 0 ℃ to 80 ℃.
The N 1 -benzyl aryl hydrazine compound is an important scaffold material, widely exists in natural products and drug molecules with biological activity, and is an important component of N-substituted indole in organic synthesis. Therefore, the N 1 -benzyl aryl hydrazine compound can be used for preparing indole compounds. For example, the indole compound can be obtained by reacting the N 1 -benzyl aryl hydrazine compound and the ketone compound in a solvent in the presence of acetic acid.
Some exemplary embodiments are described below.
Example 1:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
117.9 mg triphenylphosphine, 204.3 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and a stirrer are added into a clean 50 mL round bottom flask, 2.0 mL dichloromethane is added under the protection of nitrogen, stirring is carried out under normal temperature conditions, after 1 minute, 97.2 mg phenylhydrazine and 32.4 mg benzyl alcohol are added into the flask, the reaction is carried out for 30 minutes under the conditions, and a TLC (thin layer chromatography) point plate is used for monitoring; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product was a yellow oily liquid with a yield of 82%.
The nuclear magnetism and high resolution mass spectrum data of compound 3aa are shown below ：1H NMR (400 MHz, CDCl3) δ 7.28 (dq, J = 15.9, 7.4 Hz, 7H), 7.08 (d, J = 8.0 Hz, 2H), 6.80 (t, J = 7.1 Hz, 1H), 4.57 (s, 2H), 3.49 (s, 2H).（ as shown in FIG. 1 and ）;13C NMR (101 MHz, CDCl3) δ 151.8, 137.6, 129.1, 128.7, 127.9, 127.4, 118.6, 113.7, 60.4.（ as shown in FIG. 2 ）; HRMS (ESI) m/z calcd for C13H14N2 +[M + H]+: 199.1230, found: 199.1229.
Example 2:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
In a clean 50 mL round bottom flask were added 235.8 mg triphenylphosphine, 204.3 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and stirrer, under oxygen protection then 2.0 mL petroleum ether, stirring at 60 ℃ for 3 min, then 109.8 mg p-methyl phenylhydrazine, 32.4 mg benzyl alcohol were added to the inside, reacting for 3 min, TLC plate monitoring; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product is yellow oily liquid with 57 percent of yield
The nuclear magnetism and high resolution mass spectrum data of compound 3ab are shown in FIG. 3 and FIG. 4 as follows ：1H NMR (600 MHz, CDCl3)δ7.29 (ddt,J= 19.8, 14.2, 7.2 Hz, 5H), 7.07 (d,J= 8.4 Hz, 2H), 6.99 (d,J= 8.4 Hz, 2H), 4.51 (s, 2H), 3.45 (s, 2H), 2.27 (s, 3H).（ and FIG. ）;13C NMR (151 MHz, CDCl3)δ149.8, 137.7, 129.6, 128.7, 128.2, 128.1, 127.4, 114.2, 61.1, 20.4.（ ）; HRMS (ESI) m/z calcd for C14H16N2 +[M + H]+: 213.1386, found 213.1395.
Example 3:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
In a clean 50 mL round bottom flask were added 235.8 mg triphenylphosphine, 204.3 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and stirrer, 2.0 mL acetonitrile was then added under air, stirred at 30 ℃ for 3 minutes, then 124.2 mg p-methoxyphenylhydrazine, 32.4 mg benzyl alcohol were added to the inside, reacted for 3 minutes, and monitored by TLC plates; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product is black liquid, and the yield is 72 percent
The nuclear magnetism and high resolution mass spectrum data of compound 3ac are shown in FIG. 5 and FIG. 6 as follows ：1H NMR (600 MHz, CDCl3)δ7.36 – 7.25 (m, 5H), 7.07 (d,J= 9.0 Hz, 2H), 6.84 (d,J= 9.0 Hz, 2H), 4.43 (s, 2H), 3.77 (s, 3H), 3.25 (s, 2H).（ and ）;13C NMR (151 MHz, CDCl3)δ153.4, 146.4, 137.5, 128.6, 128.4, 127.5, 116.4, 114.4, 62.4, 55.7.（ ）; HRMS (ESI) m/z calcd for C14H16N2O+[M + H]+: 251.1155, found 251.1182.
Example 4:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
In a clean 50 mL round bottom flask were added 235.8 mg triphenylphosphine, 102.1 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and stirrer, under nitrogen then 2.0 mL acetonitrile under stirring at 80 ℃ for 30 minutes, then 147.6 mg p-tert-butylphenylhydrazine, 32.4 mg benzyl alcohol were added to the inside, reacted for 3 minutes under this condition, and TLC plates were monitored; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The desired product was a black solid in 28% yield.
The nuclear magnetism and high resolution mass spectrum data of compound 3ad are shown in FIG. 7 and FIG. 8 as follows ：1H NMR (400 MHz, CDCl3)δ7.36 – 7.26 (m, 7H), 7.04 (d,J= 8.8 Hz, 2H), 4.54 (s, 2H), 3.51 (s, 2H), 1.30 (s, 9H).（ and FIG. ）;13C NMR (101 MHz, CDCl3)δ149.6, 141.5, 137.9, 128.7, 128.0, 127.3, 125.9, 113.6, 60.9, 33.9, 31.5.（ ）; HRMS (ESI) m/z calcd for C17H22N2 +[M + H]+: 255.1856, found 255.1862.
Example 5:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
235.8 mg triphenylphosphine, 102.1 mg of 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and a stirrer are added into a clean 50mL round bottom flask, 2.0 mL ethyl acetate is then added under air, stirring is carried out at normal temperature, after 30 minutes, 124.2 mg phenylhydrazine and 36.6 mg p-methylbenzyl alcohol are added into the flask, and the reaction is carried out for 1 hour and minutes under the condition, and TLC (thin layer chromatography) point plates are monitored; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product is yellow oily liquid with 67 percent of yield
The nuclear magnetism and high resolution mass spectrum data of compound 3ba are shown in FIG. 9 and FIG. 10 as follows ：1H NMR (400 MHz, CDCl3)δ7.25 (t,J= 7.9 Hz, 2H), 7.20 (d,J= 8.5 Hz, 2H), 7.11 (d,J= 8.1 Hz, 2H), 6.88 (s, 2H), 6.80 (t,J= 7.2 Hz, 1H), 4.49 (s, 2H), 3.87 – 3.83 (m, 4H), 3.47 (s, 2H), 3.16 – 3.11 (m, 4H).（ and FIG. ）;13C NMR (101 MHz, CDCl3)δ151.9, 150.7, 129.1, 129.0, 128.6, 118.6, 115.8, 114.0, 66.9, 59.9, 49.4.（ ）; HRMS (ESI) m/z calcd for C14H16N2 +[M + H]+: 235.1205, found 235.1202.
Example 6:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
78.6 mg triphenylphosphine, 102.1 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and a stirrer are added into a clean 50 mL round bottom flask, 2.0 mL ethyl acetate is then added under the protection of nitrogen, stirring is carried out at the temperature of 0 ℃ for 1 hour, 124.2 mg phenylhydrazine and 55.2 mg p-phenylbenzyl alcohol are added into the flask, the reaction is carried out for 3 minutes under the condition, and a TLC (thin layer chromatography) plate is monitored; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product is yellow solid with the yield of 72%
The nuclear magnetism and high resolution mass spectrum data of compound 3ca are shown in FIG. 11 and FIG. 12 as ：1H NMR (400 MHz, CDCl3)δ7.56 (t,J= 7.7 Hz, 4H), 7.46 – 7.23 (m, 7H), 7.10 (d,J= 8.0 Hz, 2H), 6.82 (t,J= 7.3 Hz, 1H), 4.61 (s, 2H), 3.57 (s, 2H).（ results FIG. 11 and FIG. ）;13C NMR (101 MHz, CDCl3)δ151.8, 140.8, 140.4, 136.7, 129.2, 128.8, 128.4, 127.5, 127.3, 127.1, 118.7, 113.7, 60.1.（ results ）; HRMS (ESI) m/z calcd for C19H18N2 +[M + H]+: 275.1543, found 275.1546.
Example 7:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
In a clean 50mL round bottom flask were added 235.8 mg triphenylphosphine, 204.3 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and stirrer, under oxygen then 2.0 mL petroleum ether, stirred at 30 ℃ for 30 minutes, then 124.2 mg phenylhydrazine, 57.9 mg 4-morpholinyl benzyl alcohol were added to the inside, reacted for 30 minutes, and TLC plates were monitored; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product was a black solid in 51% yield.
The nuclear magnetism and high resolution mass spectrum data of compound 3da are shown in FIG. 13 and FIG. 14 as follows ：1H NMR (400 MHz, CDCl3)δ7.25 (t,J= 7.9 Hz, 2H), 7.20 (d,J= 8.5 Hz, 2H), 7.11 (d,J= 8.1 Hz, 2H), 6.88 (s, 2H), 6.80 (t,J= 7.2 Hz, 1H), 4.49 (s, 2H), 3.87 – 3.83 (m, 4H), 3.47 (s, 2H), 3.16 – 3.11 (m, 4H).（ and FIG. ）;13C NMR (101 MHz, CDCl3)δ151.9, 150.7, 129.1, 129.0, 128.6, 118.6, 115.8, 114.0, 66.9, 59.9, 49.4. （ ）; HRMS (ESI) m/z calcd forC17H21N3O+[M + H]+: 284.1758, found 284.1764.
Example 8:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
235.8 mg triphenylphosphine, 204.3 mg of 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and a stirrer are added into a clean 50 mL round bottom flask, 2.0 mL ethyl acetate is then added under the protection of nitrogen, stirring is carried out at 60 ℃ for 3 minutes, 124.2 mg phenylhydrazine and 42.6 mg p-chlorobenzyl alcohol are added into the flask, the reaction is carried out for 30 minutes under the condition, and a TLC (thin layer chromatography) plate is monitored; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The desired product was a black solid in 86% yield.
The nuclear magnetism and high resolution mass spectrum data of compound 3ea are shown below ：1H NMR (400 MHz, CDCl3)δ7.32 – 7.22 (m, 6H), 7.05 (d,J= 7.9 Hz, 2H), 6.83 (t,J= 7.3 Hz, 1H), 4.56 (s, 2H), 3.56 (s, 2H).（ as shown in FIG. 15 and ）;13C NMR (151 MHz, CDCl3)δ151.6, 136.3, 133.1, 129.2, 129.2, 128.8, 118.9, 113.6, 59.8.（ as shown in FIG. 16), HRMS (ESI) M/z calcd for C 13H13N2 Cl+ [ M+H ] +: 233.0840, found 233.0845.
Example 9:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
to a clean 50 mL round bottom flask was added 235.8 mg triphenylphosphine, 204.3 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and stirrer, 2.0 mL ethyl acetate under nitrogen, stirred at 60 ℃ for 30 minutes, then added 124.2 mg phenylhydrazine, 64.8mg p-phenylsulfanylbenzyl alcohol, reacted for 3 minutes under this condition, and monitored by TLC plates; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product was a yellow oily liquid with a yield of 72%.
The nuclear magnetism and high resolution mass spectrum data of the compound 3fa are shown in FIG. 17 and FIG. 18 as follows ：1H NMR (600 MHz, CDCl3)δ7.36 – 7.32 (m, 2H), 7.31 – 7.19 (m, 9H), 7.09 – 7.00 (m, 2H), 6.81 (t,J= 7.3 Hz, 1H), 4.55 (s, 2H), 3.56 (s, 2H).（ and ）;13C NMR (151 MHz, CDCl3)δ151.6, 136.8, 135.7, 134.8, 131.3, 131.1, 129.2, 129.1, 128.7, 127.1, 118.7, 113.5, 59.9.（ ）; HRMS (ESI) m/z calcd for C19H18N2S+[M + H]+: 307.1264, found 307.1258.
Example 10:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
176.9 mg triphenylphosphine, 102.1 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and a stirrer are added into a clean 50 mL round bottom flask, 2.0 mL petroleum ether is then added under air, stirring is carried out under normal temperature conditions, after 30 minutes, 124.2 mg phenylhydrazine and 55.8mg p-bromobenzyl alcohol are added into the flask, the reaction is carried out for 30 minutes under the conditions, and TLC point plates are monitored; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product was a black liquid with a yield of 69%.
The nuclear magnetism and high resolution mass spectrum data of compound 3ga are shown in FIG. 19 and FIG. 20 as follows ：1H NMR (400 MHz, CDCl3)δ7.45 (d,J= 8.3 Hz, 2H), 7.29 – 7.24 (m, 2H), 7.18 (d,J= 8.2 Hz, 2H), 7.04 (d,J= 8.0 Hz, 2H), 6.83 (t,J= 7.3 Hz, 1H), 4.54 (s, 2H), 3.59 (s, 2H).（ and ）;13C NMR (151 MHz, CDCl3)δ151.6, 136.8, 131.8, 129.6, 129.2, 121.2, 118.9, 113.6, 59.8. （ ）;HRMS (ESI) m/z calcd for C13H13N2Br+[M + H]+: 277.0335, found 277.0332.
Example 11:
The preparation method of the N 1 -benzyl substituted aryl hydrazine compound comprises the following steps:
176.9mg triphenylphosphine, 68.1 mg 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) and a stirrer are added into a clean 50 mL round bottom flask, 2.0 mL ethyl acetate is then added under air, stirring is carried out at normal temperature, after 30 minutes, 124.2 mg phenylhydrazine and 52.2mg 4-pyrazol-1-yl benzyl alcohol are added into the flask, the reaction is carried out for 3 minutes under the condition, and a TLC point plate is monitored; after the reaction is finished, the reaction solution is added with water and extracted for 3 times by ethyl acetate, and the organic layer is concentrated and separated by column chromatography to obtain the target product. The target product is black solid with the yield of 78%
The nuclear magnetism and high resolution mass spectrum data of compound 3ha are shown in FIG. 21 and FIG. 22 as follows ：1H NMR (600 MHz, CDCl3)δ7.89 (d,J= 2.4 Hz, 1H), 7.71 (d,J= 1.4 Hz, 1H), 7.65 (d,J= 8.5 Hz, 2H), 7.37 (d,J= 8.4 Hz, 2H), 7.29 – 7.24 (m, 2H), 7.08 (d,J= 8.1 Hz, 2H), 6.83 (t,J= 7.3 Hz, 1H), 6.47 – 6.42 (m, 1H), 4.60 (s, 2H), 3.61 (s, 2H).（ and FIG. ）;13C NMR (151 MHz, CDCl3)δ151.6, 141.1, 139.5, 136.0, 129.2, 129.0, 126.8, 119.5, 118.8, 113.7, 107.6, 59.9.（ ）; HRMS (ESI) m/z calcd for C13H14N2 +[M + Na]+: 287.1267, found 287.1271.
Example 12:
In this example, an indole compound 4a was synthesized using the N 1 -benzyl substituted aryl hydrazines compound 3aa prepared in example 1, and the preparation method includes the following steps:
29.4 mg cyclohexanone and a stirrer are added into a 50 mL round bottom flask, 60 mg3aa are then added, stirring is carried out at 70 ℃, 2.5 mL acetic acid is added to the flask, the reaction is carried out for 12 hours under the condition, and a TLC plate is used for monitoring; after the reaction is finished, the reaction solution is extracted for 3 times by ethyl acetate after adding water, and the pure target product 4a is obtained after the concentration of an organic layer and separation by column chromatography, and the yield is 84 percent.
The nuclear magnetism and high resolution mass spectrum data of compound 4a are shown in FIG. 24 below ：1H NMR (400 MHz, CDCl3)δ7.77 – 7.63 (m, 1H), 7.47 – 7.33 (m, 4H), 7.32 – 7.24 (m, 2H), 7.20 – 7.12 (m, 2H), 5.36 (s, 2H), 2.95 (t, J = 5.7 Hz, 2H), 2.78 (t, J = 5.8 Hz, 2H), 2.14 – 1.98 (m, 4H);13C NMR (101 MHz, CDCl3)δ138.5, 136.8, 135.7, 128.8, 127.7, 127.3, 126.3, 120.9, 119.0, 117.9, 110.0, 109.1, 46.3, 23.4, 23.4, 22.3, 21.3.（, HRMS (ESI) m/z calcd for C 19H19N+[M + H]+ 262.1590, found 262.1603.
In conclusion, the purity of the target product prepared by the preparation method provided by the invention is high, the yield can reach 51% -86%, wherein the yields of the compounds 3aa and 3ea are the highest (reach 86%), and the yield of the indole compound 4a synthesized by taking the compound as a raw material reaches 84%, so that the purity of the target product prepared by the preparation method provided by the invention is high, and the conversion rate is high. N 1 -benzyl substituted aryl hydrazine compounds prepared in example 1-example 11 can be used for organic synthesis of N-substituted indole.
The present invention is not limited to the above embodiments, but is merely preferred embodiments of the present invention, and the present invention should be considered as being within the scope of the present invention as long as the technical effects of the present invention are achieved by the same or equivalent means. Various modifications and variations are possible in the technical solution and/or in the embodiments within the scope of the invention.

Claims (10)

  1. N 1 -benzyl aryl hydrazine compounds are characterized by having a structure shown in a formula III:
    the compound of the formula III,
    Wherein R, R' is independently selected from hydrogen, alkyl, groups containing mono-or poly-substituted electron donating and electron withdrawing effects.
  2. 2. The N 1 -benzyl arylhydrazines of claim 1 wherein the R, R' is independently selected from the group consisting of hydrogen, C 1-C18 alkyl, C 1-C18 alkoxy, phenyl, naphthyl, morpholinyl, halogen atoms, phenylthio, pyrazolyl.
  3. 3. The N 1 -benzyl arylhydrazines of claim 1 wherein the R, R' is independently selected from the group consisting of hydrogen, methyl, ethyl, N-propyl, isopropyl, N-butyl, isobutyl, t-butyl, methoxy, ethoxy, phenyl, naphthyl, morpholinyl, fluoro, chloro, bromo, iodo, phenylthio, pyrazolyl.
  4. 4. The N 1 -benzyl arylhydrazines compound according to claim 1, wherein the N 1 -benzyl arylhydrazines compound is one of the compounds represented by the following formula:
    。
  5. 5. The method for preparing the N 1 -benzyl arylhydrazines according to claim 1, comprising the steps of:
    Under the participation of triphenylphosphine and 2, 3-dichloro-5, 6-dicyanobenzoquinone, enabling benzyl alcohol compounds shown in a formula I and aryl hydrazine compounds shown in a formula II to react in a solvent to obtain N 1 -benzyl aryl hydrazine compounds shown in a formula III;
    Wherein R, R' is independently selected from hydrogen, alkyl, groups containing mono-or poly-substituted electron donating and electron withdrawing effects.
  6. 6. The method according to claim 5, wherein the molar ratio of the arylhydrazine compound of formula II to the benzyl alcohol compound of formula I is (1-3): 1.
  7. 7. The method according to claim 5, wherein the solvent is petroleum ether, dichloromethane, acetonitrile or ethyl acetate.
  8. 8. The method of claim 5, wherein the reaction is performed under an oxygen, air or nitrogen atmosphere.
  9. 9. The method of claim 5, wherein the reaction is carried out at 0 ℃ to 80 ℃.
  10. 10. The use of an N 1 -benzyl arylhydrazines according to claim 1 for the preparation of indoles.
CN202410306683.7A 2024-03-18 2024-03-18 N1-Benzyl aryl hydrazine compound, and preparation method and application thereof Pending CN118206466A (en)

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