CN115215764B - Preparation method of deuterated aromatic nitrile compound - Google Patents

Preparation method of deuterated aromatic nitrile compound Download PDF

Info

Publication number
CN115215764B
CN115215764B CN202210812275.XA CN202210812275A CN115215764B CN 115215764 B CN115215764 B CN 115215764B CN 202210812275 A CN202210812275 A CN 202210812275A CN 115215764 B CN115215764 B CN 115215764B
Authority
CN
China
Prior art keywords
deuterated
aromatic nitrile
deuteration
compound
solvent
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.)
Active
Application number
CN202210812275.XA
Other languages
Chinese (zh)
Other versions
CN115215764A (en
Inventor
摆建飞
吴涛
江之江
高章华
刘嫣然
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.)
Ningbo Cuiying Chemical Technology Co ltd
Zhejiang University of Science and Technology ZUST
Original Assignee
Ningbo Cuiying Chemical Technology Co ltd
Zhejiang University of Science and Technology ZUST
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 Ningbo Cuiying Chemical Technology Co ltd, Zhejiang University of Science and Technology ZUST filed Critical Ningbo Cuiying Chemical Technology Co ltd
Priority to CN202210812275.XA priority Critical patent/CN115215764B/en
Publication of CN115215764A publication Critical patent/CN115215764A/en
Application granted granted Critical
Publication of CN115215764B publication Critical patent/CN115215764B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/001—Acyclic or carbocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/002—Heterocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

Landscapes

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

Abstract

The invention discloses a preparation method of deuterated aromatic nitrile compounds, which takes the aromatic nitrile compounds shown in the formula (I) as raw materials, under the protection of inert atmosphere, aryl methylimino acid ester is firstly generated in situ with aliphatic alcohol compounds in a catalytic system, then hydrogen-deuterium exchange reaction is carried out with deuteration reagent, then in situ hydrolysis is carried out to obtain aromatic nitrile ortho-position deuteration compounds, and finally, products are separated and purified; the catalytic system comprises a metal catalyst, an auxiliary agent, an oxidant and a solvent. The invention has the advantages of high operability and good deuteration effect.

Description

Preparation method of deuterated aromatic nitrile compound
Technical Field
The invention relates to the technical field of synthesis of deuterated compounds, in particular to a preparation method of deuterated aromatic nitrile compounds.
Background
Deuterium is a stable form of nonradioactive isotope of hydrogen in nature, and carbon-deuterium bonds are more stable (6-9 times) than carbon-hydrogen bonds due to its greater atomic mass than hydrogen. In recent years, with research on deuterated compounds, it has been found that substitution of hydrogen in a drug molecule with deuterium can block metabolic sites and reduce the generation of toxic metabolites. Furthermore, deuteration can slow down the systemic clearance rate and thus extend the half-life of the drug in vivo. Therefore, the aim of reducing the toxic and side effects of the drug can be achieved by reducing the single administration dose while the pharmacological activity of the drug is not affected. Due to the special pharmacokinetic properties of deuterated drugs, the development speed of deuterated drugs has increased in recent years, and the demand for deuteration strategies for various active compounds has also increased.
Cyano groups have good biocompatibility and can often penetrate deep into target proteins to form hydrogen bond interaction with key amino acid residues of active sites; meanwhile, cyano can also be used as a metabolism blocking site to inhibit the oxidative metabolism of small molecules and improve the metabolic stability of the compound in vivo. As an important organic drug group, aromatic nitrile and its derivatives have been widely used in medicine and the like.
Verapamil is, for example, a calcium channel blocker for treating hypertension, angina pectoris, arrhythmia, cerebrovascular disease and the like; the febuxostat has remarkable inhibition effect on the oxidation type and the reduction type XOR, so that the effect of reducing uric acid is stronger and lasting, and the febuxostat can be used for treating chronic hyperuricemia caused by gout; itravirin is a new generation of non-nucleoside reverse transcriptase inhibitors, which can greatly reduce the morbidity and mortality of aids; pirenzenenaphthalene is commonly used for additive treatment of adult and partial seizure patients in children 12 years old and older (with or without secondary generalized seizures); the antitumor drug 2- (4-substituted piperazine-1-yl) methylbenzonitrile has stronger inhibition rate on tumor strain Skov3 (human ovarian cancer) than other tumor strains; bicalutamide is used for the treatment of advanced prostate cancer.
At present, the deuteration research on the aromatic ring of the aromatic nitrile derivative is still in the starting stage. Because the nitrile carbon-nitrogen triple bond is in a linear structure, the catalyst is difficult to form a cyclic metal transition state with nitrogen atoms and ortho-position hydrogen atoms on an aromatic ring to catalyze the reaction, and therefore, the catalyst has a great challenge for the aromatic nitrile compound ring, namely the C-H activation reaction and the H/D exchange reaction. In addition, cyano groups are a type of active functional groups in organic synthesis, can be converted into other functional groups or heterocycles, and have low tolerance to reaction conditions.
Few reports are currently made about the preparation method of deuterated aromatic nitrile derivatives. Dieter Muri et al in 2014 indirectly obtained deuterated aromatic nitrile products by deuterated amides using iridium metal complexes. The reaction needs to use deuterium as a deuterium source, and the catalyst has a complex structure and high price, so that the application range of the catalyst is greatly limited;
。
disclosure of Invention
The invention aims to provide a preparation method of deuterated aromatic nitrile compounds, which has the advantages of high operability and good deuteration effect.
The technical scheme adopted for solving the technical problems is as follows:
the preparation method of deuterated aromatic nitrile compound is characterized in that the aromatic nitrile compound shown in the formula (I) is used as a raw material, aryl methylimino acid ester is firstly generated in situ with aliphatic alcohol compounds in a catalytic system under the protection of inert atmosphere, then hydrogen-deuterium exchange reaction is carried out with deuteration reagent, then in-situ hydrolysis is carried out to obtain the aromatic nitrile ortho-deuteration compound, and finally, the product is separated and purified; the catalytic system comprises a metal catalyst, an auxiliary agent, an oxidant and a solvent;
。
the invention uses cheap metal as catalyst, uses one-pot two-step method, and has simple operation and higher hydrogen-deuterium exchange degree without separating intermediate. Has the characteristics of better operability and stability, high catalytic efficiency, high economic benefit, simple and convenient operation, easy separation of products and the like.
Preferably, the deuterated reagent is one of heavy water, deuterated methanol and deuterated benzene. More preferably heavy water.
Preferably, the inert atmosphere is a gaseous atmosphere composed of nitrogen or argon.
Preferably, the metal catalyst is selected from one of manganese decacarbonyl, manganese pentacarbonyl bromide, manganese acetate, cobalt hydroxide, ferric oxide and ferric oxide. When manganese pentacarbonyl bromide is used, the highest deuteration degree can reach 98%.
Preferably, the auxiliary agent is one of sodium acetate, potassium acetate, sodium oxalate, sodium carbonate and potassium carbonate. When sodium acetate is selected, the highest deuteration degree can reach 95%. The addition of the auxiliary agent can effectively promote the exchange rate of hydrogen and deuterium in the reaction process and improve the deuteration degree of the reaction.
Preferably, the solvent isN-one of methyl pyrrolidone, tetrahydrofuran, dioxane, cyclohexane, cyclopentyl methyl ether. Preferably N-methyl pyrrolidone, and when the solvent is selected, the highest deuteration degree of the product can reach 95 percent.
Preferably, the oxidant is one of sodium hypochlorite, hydrogen peroxide, peracetic acid, sodium dichromate, sodium perborate, potassium perborate, and methyl hypochlorite. When sodium hypochlorite is selected, the highest deuteration degree can reach 95%. The addition of the oxidant can promote the nitrile compound and the alcohol to generate aryl azomethionate in situ.
Preferably, the fatty alcohol compound is one of methanol, ethanol, isopropanol, tertiary butanol and benzyl alcohol. When ethanol is selected, the highest deuteration degree can reach 98 percent.
Preferably, the molar ratio of the materials is aromatic nitrile compound: fatty alcohol compounds: oxidizing agent: deuterated reagent: metal catalyst: auxiliary agent: solvent = 1: 1.1: 1: 10-500: 0.05-0.20:1: 20-500.
Preferably, the R 1 Is alkyl, alkoxy, vinyl, aromatic substituent, nitro, amino, triOne or more of fluoromethyl, halogen, pyridine, thiophene and furan; the R is 2 Is one or more of benzyl, methyl, ethyl, isopropyl, tertiary butyl, alkoxy, allyl and tertiary butyl. The alkyl group may be saturated hydrocarbon of 1-6 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclobutyl, etc. The aromatic substituent may be phenyl, naphthalene, etc.
The beneficial effects of the invention are as follows: according to the invention, the transition metal is utilized to activate the aromatic nitrile compound, the aryl methylimino acid ester intermediate is formed, and the deuteration reagent is taken as a deuteration source to realize the deuteration reaction of the aromatic nitrile compound, so that the synthesis of the deuteration product is realized, the operability is high, the operation is convenient, and the cost is low.
The method is completed under the condition of a conventional laboratory by adopting a technical route, the solvent does not need to be replaced halfway in the one-pot reaction, the reaction operability is high, the deuteration effect is good, the selectivity is good, and the application range is wide.
The process method has good universality, can be used for preparing deuterated products of various aromatic nitrile compounds, and is also applicable to various aromatic nitrile medicaments.
Detailed Description
The technical scheme of the invention is further specifically described by the following specific examples.
In the present invention, the materials and equipment used are commercially available or commonly used in the art, unless otherwise specified. The methods in the following examples are conventional in the art unless otherwise specified.
General embodiment
The preparation method of deuterated aromatic nitrile compound is characterized in that the aromatic nitrile compound shown in the formula (I) is used as a raw material, aryl methylimino acid ester is firstly generated in situ with aliphatic alcohol compounds in a catalytic system under the protection of inert atmosphere, then hydrogen-deuterium exchange reaction is carried out with deuteration reagent, then in-situ hydrolysis is carried out to obtain the aromatic nitrile ortho-deuteration compound, and finally, the product is separated and purified; the catalytic system comprises a metal catalyst, an auxiliary agent, an oxidant and a solvent;
；
the deuterated reagent is one of heavy water, deuterated methanol and deuterated benzene; the inert atmosphere is a gas environment formed by nitrogen or argon; the metal catalyst is selected from one of manganese decacarbonyl, manganese pentacarbonyl bromide, manganese acetate, cobalt hydroxide, ferric oxide and ferroferric oxide; the auxiliary agent is one of sodium acetate, potassium acetate, sodium oxalate, sodium carbonate and potassium carbonate; the solvent isN-one of methyl pyrrolidone, tetrahydrofuran, dioxane, cyclohexane, cyclopentyl methyl ether; the oxidant is one of sodium hypochlorite, hydrogen peroxide, peracetic acid, sodium dichromate, sodium perborate, potassium perborate and methyl hypochlorite; the fatty alcohol compound is one of methanol, ethanol, isopropanol, tertiary butanol and benzyl alcohol.
The molar usage ratio of the materials is that the aromatic nitrile compound: fatty alcohol compounds: oxidizing agent: deuterated reagent: metal catalyst: auxiliary agent: solvent = 1: 1.1: 1: 10-500: 0.05-0.20:1: 20-500.
The R is 1 Is one or more of alkyl, alkoxy, vinyl, aromatic substituent, nitro, amino, trifluoromethyl, halogen, pyridine, thiophene and furan; the R is 2 Is one or more of benzyl, methyl, ethyl, isopropyl, tertiary butyl, alkoxy, allyl and tertiary butyl.
Example 1 synthesis of benzonitrile ortho-deuterated product:
under nitrogen atmosphere, 15 mL dry sealed tube was taken, benzonitrile (103 mg, 1 mmol) and sodium hypochlorite (150 mg, 2 mmol) were added sequentially, ethanol (0.1 mL) was slowly added dropwise with stirring, and the reaction solution was reacted at room temperature for 24 hours (arylmethylimino acid ester was prepared in situ). To the reaction mixture was then added manganese carbonyl bromide (27.5 mg, 0.1 mmol), sodium acetate (82 mg, 1 mmol), N-methylpyrrolidone: heavy water=0.5/0.5 mL (v/v=1/1), and reacted at 100 ℃ for 0.5 hours. After the reaction, 5 ml of 1N aq HCl was added and stirred at room temperature for about 1 hour (hydrolysis of aryl azomethionate to give aromatic nitrile). With 10The ethyl acetate is extracted for 2 to 3 times, the organic phase is dried and concentrated to obtain a crude product. The crude product is purified by column chromatography to obtain the benzonitrile ortho-deuterated product. 1 H NMR (500 MHz, Chloroform-d)δ7.62 (m, 1H), 7.60-7.54 (m, 0.2 H), 7.49-7.47 (m, 2H)。
Under the same conditions, starting from each substituted aromatic nitrile derivative, derivative 1 (deuterated product of the aromatic nitrile derivative represented by formula II) was obtained under the above conditions, and the results are shown in the following table:
。
deuterated 4-aminophenylacetonitrile, 2-d
1 H NMR (500 MHz, Chloroform-d) δ 6.94-6.92 (m, 0.18 H, Labelled), 6.57-6.55 (m, 2H), 3.62(t, J = 1.0 Hz, 2H), 3.16 (brs, 2H).
Deuterated 4-fluorobenzonitrile, 3-d
1 H NMR (500 MHz, Chloroform-d) δ 7.61-7.57 (m, 0.2H, Labelled), 7.15-7.09 (m, 2H).
Deuterated 3, 5-diaminobenzonitrile, 4-d
1 H NMR (500 MHz, Chloroform-d) δ 6.83-6.73 (m, 0.22H, Labelled), 5.44 (s, 1H), 4.35 (brs, 4H).
Deuterated 2-bromomethyl-4-fluorobenzonitrile, 5-d
1 H NMR (500 MHz, Chloroform-d) δ 7.66-7.58 (m, 0.07H, Labelled), 7.10 (d, J = 16.5 Hz, 1H), 7.08 (m, 1H), 4.51 (d, J = 1.1 Hz, 2H).
Deuterated 4-amino-2-methoxybenzonitrile, 6-d
1 H NMR (500 MHz, Chloroform-d) δ 7.42-7.40 (m, 0.13H, Labelled), 6.42-6.37 (m, 2H), 4.40 (brs, 2H), 3.92(s, 3H).
Deuterated 4-phenoxybenzonitrile, 7-d
1 H NMR (500 MHz, Chloroform-d) δ 7.74-7.69 (m, 0.26H, Labelled), 7.37-7.32 (m, 2H), 7.18-7.13 (m, 2H), 7.09(tt, J = 9.0, 2.0 Hz, 1H), 7.03-7.01 (m, 2H).
Deuterated 4-morpholinyl benzonitrile, 8-d
1 H NMR (500 MHz, Chloroform-d) δ 7.13-7.07 (m, 0.16H, Labelled), 6.87-6.80 (m, 2H), 3.89-3.83 (m, 4H),3.19-3.13 (m, 4H).
Deuterated 3-benzyloxy-4-methoxybenzonitrile, 9-d
1 H NMR (500 MHz, Chloroform-d) δ 7.45-7.43 (m, 0.06H, Labelled), 7.40-7.37 (m, 4H), 7.35-7.34 (m, 0.11H, Labelled), 7.33-7.29 (m, 1H),7.26-7.24 (m, 1H), 5.15 (t,J= 1.0 Hz, 2H), 3.87 (s, 3H).
Deuterated febuxostat, 10-d
1 H NMR (500 MHz, Chloroform-d) δ 8.26 (d,J= 2.1 Hz, 1H), 8.19-8.17 (m, 1H), 7.22-7.20 (m, 0.1H, Labelled), 3.96 (d,J= 5.0 Hz, 2H), 2.85-2.77 (m, 1H), 2.68 (s, 3H), 1.15 (d,J= 7.2 Hz, 6H)。
The above-described embodiment is only a preferred embodiment of the present invention, and is not limited in any way, and other variations and modifications may be made without departing from the technical aspects set forth in the claims.

Claims (4)

1. A preparation method of deuterated aromatic nitrile compound is characterized in that aromatic nitrile compound shown in formula (I) is used as raw material, aryl methylimino acid ester is generated with aliphatic alcohol compound in situ in a catalytic system under the protection of inert atmosphere, then hydrogen-deuterium exchange reaction is carried out with deuteration reagent, then in-situ hydrolysis is carried out to obtain aromatic nitrile ortho-deuteration compound, and finally, the product is separated and purified; the catalytic system comprises a metal catalyst, an auxiliary agent, an oxidant and a solvent;
；
the metal catalyst is selected from one of manganese decacarbonyl, manganese pentacarbonyl bromide and manganese acetate;
the saidThe oxidant is sodium hypochlorite; the fatty alcohol compound is one of methanol, ethanol, isopropanol, tertiary butanol and benzyl alcohol; the molar usage ratio of the materials is that the aromatic nitrile compound: fatty alcohol compounds: oxidizing agent: deuterated reagent: metal catalyst: auxiliary agent: solvent = 1: 1.1: 1: 10-500: 0.05-0.20:1: 20-500; the R is 1 Is one or more of alkyl, alkoxy, vinyl, nitro, amino, trifluoromethyl, halogen, pyridine, thiophene and furan.
2. The method of claim 1, wherein the deuterating agent is one of heavy water, deuterated methanol, deuterated benzene.
3. The method according to claim 1, wherein the inert atmosphere is a gaseous atmosphere composed of nitrogen or argon.
4. The method according to claim 1, wherein the solvent isN-one of methyl pyrrolidone, tetrahydrofuran, dioxane, cyclohexane, cyclopentyl methyl ether.
CN202210812275.XA 2022-07-11 2022-07-11 Preparation method of deuterated aromatic nitrile compound Active CN115215764B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210812275.XA CN115215764B (en) 2022-07-11 2022-07-11 Preparation method of deuterated aromatic nitrile compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210812275.XA CN115215764B (en) 2022-07-11 2022-07-11 Preparation method of deuterated aromatic nitrile compound

Publications (2)

Publication Number Publication Date
CN115215764A CN115215764A (en) 2022-10-21
CN115215764B true CN115215764B (en) 2023-12-08

Family

ID=83612052

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210812275.XA Active CN115215764B (en) 2022-07-11 2022-07-11 Preparation method of deuterated aromatic nitrile compound

Country Status (1)

Country Link
CN (1) CN115215764B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0782252A (en) * 1993-06-30 1995-03-28 Fuji Photo Film Co Ltd Production of imidic acid ester compound and n-pyrazolylamidoxime compound
CN104529823A (en) * 2014-10-23 2015-04-22 江苏南方农药研究中心 Benzimidate compound preparation method
CN108675942A (en) * 2018-06-19 2018-10-19 杭州盛漫生物科技有限公司 A kind of preparation method of aromatic nitrile compounds

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220024925A1 (en) * 2020-07-22 2022-01-27 Acurx Pharmaceuticals Llc Deuterium-Substituted 7-Substituted-2-(Benzylamino)-6-Ozopurine Compounds and Uses Thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0782252A (en) * 1993-06-30 1995-03-28 Fuji Photo Film Co Ltd Production of imidic acid ester compound and n-pyrazolylamidoxime compound
CN104529823A (en) * 2014-10-23 2015-04-22 江苏南方农药研究中心 Benzimidate compound preparation method
CN108675942A (en) * 2018-06-19 2018-10-19 杭州盛漫生物科技有限公司 A kind of preparation method of aromatic nitrile compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Manganese-Catalyzed ortho-C-H Alkenylation of Aromatic N-H Imidates with Alkynes: Versatile Access to Mono-Alkenylated Aromatic Nitriles.;Xiaoxu Yang，et al.;《Adv. Synth. Catal.》;第358卷;2436- 2442 *
Manganese-catalyzed selective C–H activation and deuteration by means of a catalytic transient directing group strategy;Sara Kopf，et al.;《Chem. Commun.》;第57卷;1137-1140 *

Also Published As

Publication number Publication date
CN115215764A (en) 2022-10-21

Similar Documents

Publication Publication Date Title
KR20170117027A (en) Commercially viable synthesis of cantharidin and bioactive cantharidin derivatives
Ni et al. A convenient access to allylic triflones with allenes and triflyl chloride in the presence of (EtO) 2P (O) H
CN115215764B (en) Preparation method of deuterated aromatic nitrile compound
CN108794412B (en) Preparation method of 4, 5-diaryl-2H-1, 2, 3-triazole compound
Qian et al. Electrochemical oxythiocyanation of ortho-olefinic amides: Access to diverse thiocyanated benzoxazines
CN112301370B (en) Electrochemical synthesis method of 1, 3-dimethyl-3-difluoroethyl-2-oxindole compound
Zhang et al. Iron/TEMPO-catalyzed direct aerobic oxidative coupling of methyl-mubstituted N-heteroazaarenes with alcohols
CN107118215B (en) A kind of preparation method for treating breast cancer medicines Rui Boxini intermediate
CN111747858B (en) Method for constructing C-N bond through insertion reaction of nonmetal-catalyzed sulfur ylide and aromatic amine and application
CN110483346B (en) Sulfonyl-substituted alpha-cyclopropylstyrene compound and synthesis method thereof
KR20140042805A (en) Intermediate for synthesizing caspofungin and preparation method therefor
JP2009029733A (en) METHOD FOR PRODUCING alpha,beta-UNSATURATED CARBONYL COMPOUND
Zhou et al. New conformationally flexible and recyclable aryl iodine catalysts from an inexpensive chiral source for asymmetric oxidations
CN109369514A (en) A kind of synthetic method of six-membered carbon ring derivative
CN113754605A (en) Nitrogen-containing ligand and preparation method and application thereof
CN110845363A (en) O-alkenyl aromatic nitrile compound and preparation method thereof
CN115286547B (en) Method for synthesizing aryl benzyl thioether compound
CN110627723A (en) Trifluoromethyl pyrazole derivative and application thereof
CN105820096B (en) A kind of method for preparing substitution ethyl aryl sulfone
CN113277935B (en) Far-end halogenated alkyl ketone using HX as halogen source and synthesis method thereof
Saegusa et al. Bromocyclization of Unsaturated Thioester and Access to Functionalized Sulfur-heterocycles
CN111635372B (en) Oxazolone derivative and synthetic method thereof
JP2014148477A (en) Reaction method and novel azo compound used in the same
CN115710199B (en) Photooxidation reduction catalytic process
CN112920129B (en) 1,2, 3-triazole-2-oxide and preparation method thereof

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