CN114805152A

CN114805152A - Method for synthesizing thioamide

Info

Publication number: CN114805152A
Application number: CN202210487922.4A
Authority: CN
Inventors: 张辅民; 唐世忠
Original assignee: Lanzhou University
Current assignee: Lanzhou University
Priority date: 2022-05-06
Filing date: 2022-05-06
Publication date: 2022-07-29
Anticipated expiration: 2042-05-06
Also published as: CN114805152B

Abstract

The invention belongs to the field of synthesis of organic intermediates, and particularly relates to a synthetic method of thioamide, which comprises the following steps: (1) dissolving a nitronium salt in a nitrile compound or dissolving the nitronium salt and the nitrile compound in a solvent; (2) under the protection of argon, adding bromide at the temperature of-35-90 ℃ for reaction; (3) cooling to-35-45 ℃, and adding a vulcanizing agent for reaction; (4) after the reaction is finished, removing fixed impurities and solvent, and purifying to obtain thioamide with a structural formula

Wherein R is various substituted benzyl, linear alkyl and cycloalkyl, R ¹ Is alkyl or phenyl, orThe method has wide substrate range, good to excellent yield and relatively mild reaction conditions, and more importantly, the method realizes the synthesis of thioamide through Ritter reaction similar process for the first time and realizes thioamidation of bromo-derivative of drug molecule or perfume.

Description

Method for synthesizing thioamide

Technical Field

The invention belongs to the field of synthesis of organic intermediates, and particularly relates to a method for synthesizing thioamide.

Background

Thioamides are of great significance in the research of biological, material and chemical disciplines, and are widely applied to a plurality of related research fields. In the aspect of biological research, the compound containing the thioamide structural unit shows certain biological activity and medicinal value, and most importantly, in the polypeptide or the protein, the thioamide structural unit can be used as an amide isostere for detecting the biological activity, the physical property, the stability, the catalytic function, the structural change, the direct change of the physicochemical property and the like of a target molecule; in materials research, thioamides also exhibit their unique functionality in several respects; in the aspect of chemical research, thioamides can be widely applied to natural product synthesis, functional group conversion and heterocyclic compound synthesis as catalysts or synthons. With the continuous and intensive research on thioamides, the importance of thioamides is more and more shown, and therefore, the efficient synthesis of thioamides is always one of the important directions for the research of synthetic chemistry.

However, the current synthesis methods still have some disadvantages, which are mainly shown in that: 1) using Lawesson reagent/P ₂ S ₅ The method for converting amide into thioamide is applied to various small-scale reactions, and has the main defects of causing organic phosphorus pollution problem, difficult separation of Lawesson reagent and the like; 2) the synthesis of thioamides by oxidation using nitriles generally allows the synthesis of only primary thioamides and is generally not applicable to aliphatic nitrile substrates; 3) although thioamide can be synthesized through Beckmann rearrangement reaction, oxime needs to be prepared in advance, and the synthesis steps are complex; 4) the Friedel-Crafts reaction of isothiocyanate mainly has the problem of position selectivity; 5) the Willgeodt-Kindler reaction is generally carried out under the high-temperature condition, the yield is low, and a milder and greener improved method needs to be developed; 6) the oxidative coupling reaction of amines is generally only suitable for the synthesis of conjugated thioamides. Therefore, the development of new methods for the synthesis of thioamides is of great scientific interest, but with certain synthetic challenges.

In view of the above technical problems, the inventors have developed a method for synthesizing thioamides, which is simple in steps and can rapidly prepare thioamides without pollution.

Disclosure of Invention

In order to solve the technical problems, the invention provides the following technical scheme: a method for synthesizing thioamide, which comprises the following steps:

(1) dissolving a nitronium salt in a nitrile compound or dissolving the nitronium salt and the nitrile compound in a solvent;

(2) under the protection of argon, adding bromide at the temperature of-35-90 ℃ for reaction;

(3) cooling to-35-45 ℃, and adding a vulcanizing agent for reaction;

(4) after the reaction is finished, removing fixed impurities and solvent, and purifying to obtain thioamide with a structural formula

Wherein R is various substituted benzyl, linear alkyl and cycloalkyl, R ¹ Is alkyl or phenyl.

The phenyl in the substituted benzyl is halogenated phenyl, tert-butyl phenyl, methyl phenyl or methoxyphenyl.

Preferably, the nitronium salt of step (1) is NOBF ₄ 、NO ₂ BF ₄ 、NOPF ₆ And NOSbF ₆ The nitrile compound is one of acetonitrile, n-butyronitrile, cyclopentanenitrile, benzonitrile and cyclohexanenitrile.

Preferably, the addition amount of the nitronium salt and the nitrile compound in the step (1) is 0.6: 1 n/v; the addition amount of the nitronium salt, the nitrile compound and the solvent is 6: 20: 10 n/n/v.

Preferably, the solvent in step (1) is CH ₃ CN or CH ₃ NO ₂ 。

Preferably, the bromide in step (2) is benzyl bromide, 4-fluorobenzyl bromide, 2-fluorobenzyl bromide, 3-fluorobenzyl bromide, 4-chlorobenzyl bromide, 4-bromobenzyl bromide, 4-trifluoromethylbenzyl bromide, 4-methylbenzyl bromide, 2-methylbenzyl bromide, 3-methylbenzyl bromide, 4-tert-butylbenzyl bromide, 3-methoxybenzyl bromide, 2-bromomethylnaphthalene, 3, 5-di-tert-butylbenzyl bromide, 4-fluoro-2-methylbenzyl bromide, 4-chloro-2-fluorobenzyl bromide, (1-bromoethyl) benzene, 1-bromo-4- (1-bromoethyl) benzene, diphenylbromomethane, tert-butylbromide, bromocyclopentane, bromocycloheptane, 7-bromonorbornane, 1-bromoadamantane, 7-bromonorbornane, 3-bromobenzyl bromide, 3-methoxybenzyl bromide, 2-bromomethylnaphthalene, 3-bromomethyl bromide, 3, 5-di-tert-butylbenzyl bromide, bromonorbornane, 2-bromonorbornane, or bromonorbornane, Any one of 1-bromo-3, 5-dimethyladamantane, salbutamol bromide derivative, and ezetimibe bromide derivative.

Preferably, the reaction time in step (2) is 30 min.

Preferably, the molar ratio of bromide to nitronium salt is 1: 1.5.

Preferably, the sulfurizing reagent in step (3) is thioacetamide, thiourea or Na ₂ S, NaHS or H ₂ S。

Preferably, the solid impurities in the step (4) are removed by filtering through diatomite, and ethyl acetate is used as an eluent; distilling the filtrate under reduced pressure to remove the organic solvent; the crude product was purified by flash column chromatography on silica gel.

Preferably, the thioamide comprises

And the like.

The invention has the beneficial effects that: the invention discloses a synthesis method of thioamide, which uses nitronium salt to promote bromide, nitrile and a sulfurization reagent to synthesize various thioamides. The method has the advantages of large chemical products as raw materials, simple operation, mild reaction conditions, short reaction time, gram-scale preparation and the like, and more importantly, the method can realize thioamidation of active functional molecules.

Detailed Description

The following description of the preferred embodiments of the present invention is provided for the purpose of illustration and description, and is in no way intended to limit the invention.

Example 1

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at room temperature (20 ℃ C.) under an argon atmosphere, and reacted at room temperature (20 ℃ C.) for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (48.3mg, 73%, white crystals).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.39-7.32(m,5H),4.80(d,J＝5.2Hz,2H),2.57(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ201.0,136.2,129.1,128.5,128.3,50.8,34.3；MS(EI)m/z(％):165(52),132(21),105(32),91(100)；IR(KBr plate):3220,3069,2923,1551,1393,1341,1165,1071,940,694cm ^-1 .

example 2

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon blanket and the reaction was continued for 30min at 45 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is led into a reaction tube (the gas guide needle has obvious gas outflow) for 1 minute, and the tail gas is dissolved in copper sulfate waterThe solution was absorbed and stirring was continued at this temperature for 20 minutes. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (52.9mg, 80%, white crystals).

Example 3

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. Then the temperature is reduced to-35 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (49.6mg, 75%, white crystals).

Example 4

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Under the protection of argon, at 45 DEG CBenzyl bromide (0.4mmol, 68.4mg) was added dropwise and the reaction was continued at 45 ℃ for 30 minutes. Then the temperature is reduced to 0 ℃, and H is injected by using an air guide needle ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (46.3mg, 70%, white crystals).

Example 5

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. Then the temperature is reduced to 20 ℃, and the H is introduced by using a gas guide needle ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (43.0mg, 65%, white crystals).

Example 6

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. Then cooling to-15 deg.C, adding Na ₂ S (4.0mmol, 312.2mg) and stirring was continued at this temperature for 20 min. After the reaction is finished, diatomite is used for filtering to remove solid impurities such as elemental sulfur and the like, and ethyl acetate is used as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (19.8mg, 30%, white crystals).

Example 7

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. The temperature was then lowered to-15 ℃ and NaHS (4.0mmol, 224.2mg) was added and stirring continued at this temperature for 20 minutes. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (15.9mg, 24%, white crystals).

Example 8

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. The temperature was then reduced to-15 deg.C, thiourea (4.0mmol, 304.5mg) was added and stirring continued at this temperature for 20 minutes. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (10.0mg, 15%, white crystals).

Example 9

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. The temperature was then reduced to-15 ℃ and thioacetic amine (4.0mmol, 300.5mg) was added and stirring continued at this temperature for 20 minutes. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (50.2mg, 76%, white crystals).

Example 10

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NOBF ₄ (0.6mmol, 71.3mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Under argon, benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃. And the reaction was continued at a temperature of 45 ℃ for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (52.9mg, 80%, white crystals).

Example 11

Taking benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NOPF ₆ (0.6mmol, 106.2mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (47.6mg, 72%, white crystals).

Example 12

Taking benzyl bromide and acetonitrile as raw materials:

the dried 10mL reaction tube and the dried reagent are put into a glove box, and NOSbF is added ₄ (0.6mmol, 154.1mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (19.8mg, 30%, white crystals).

Example 13

Taking 4-fluorobenzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 4-fluorobenzyl bromide (0.4mmol, 75.6mg) was added slowly at 45 ℃ under argon and the reaction was continued for 30min at 45 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction was completed, the reaction mixture was filtered through celite to removeSolid impurities such as elemental sulfur and the like, and ethyl acetate is used as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (51.3mg, 70%, white crystals).

The product detection data were as follows: ¹ H NMR(400MHz,CDCl ₃ ):δ7.55(s,1H),7.31-7.28(m,2H),7.03(t,J＝8.4Hz,2H),4.77(d,J＝5.2Hz,2H),2.55(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ201.1,162.6(d,J＝246.0Hz),132.0(d,J＝3.0Hz),130.2(d,J＝8.0Hz),115.9(d,J＝21.0Hz),49.8,34.2；HRMS(ESI)m/z calculated for C ₉ H ₁₀ FNS[M+H] ⁺ 184.0591,found 184.0598.MS(EI)m/z(％):184(4),183(37),124(19),109(100),59(17)；IR(KBr plate):3224,3070,1555,1509,1227,1168,1079,827,729cm ^-1 .

example 14

Taking 2-fluorobenzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 2-fluorobenzyl bromide (0.4mmol, 75.6mg) was added slowly at 90 ℃ under argon and the reaction was continued for 30min at 90 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (27.5mg, 38%, yellow oily liquid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.53(s,1H),7.40(td,J＝1.6Hz,J＝7.6Hz,1H),7.34-7.28(m,1H),7.15-7.05(m,2H),4.88(d,J＝5.2Hz,2H),2.56(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ201.3,161.3(d,J＝245.0Hz),131.2(d,J＝4.0Hz),130.2(d,J＝8.0Hz),124.6(d,J＝4.0Hz),123.1(d,J＝15.0Hz),115.7(d,J＝21.0Hz),44.4(d,J＝3.0Hz),34.3；HRMS(ESI)m/z calculated for C ₉ H ₁₀ FNS[M+H] ⁺ 184.0591,found 184.0589.MS(EI)m/z(％):183(43),167(27),124(75),110(15),109(100)；IR(KBr plate):3223,3046,2929,1535,1492,1390,1336,1232,1171,1105,1075,758cm ^-1 .

example 15

3-fluorobenzyl bromide and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 3-Fluorobenzyl bromide (0.4mmol, 75.6mg) was added slowly at 90 ℃ under argon and the reaction was continued for 30min at 90 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, diatomite is used for filtering to remove solid impurities such as elemental sulfur and the like, and ethyl acetate is used as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (29.3mg, 40%, yellow oily liquid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.69(s,1H),7.34-7.30(m,1H),7.10(d,J＝7.8Hz,1H),7.03-6.99(m,2H),4.82(d,J＝5.4Hz,2H),2.57(s,3H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ201.5,163.0(d,J＝244.5Hz),138.6(d,J＝6.0Hz),130.6(d,J＝7.5Hz),123.9(d,J＝3.0Hz),115.14(d,J＝34.5Hz),115.13(d,J＝6.0Hz),49.8,34.1；MS(EI)m/z(％):184(6),183(52),164(4),124(41),109(100)；IR(KBr plate):3221,3050,2929,1592,1536,1488,1450,1387,1334,1254,1170,1069,950,787,685cm ^-1 .

example 16

4-chlorobenzyl bromide and acetonitrile are taken as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 4-chlorobenzyl bromide (0.4mmol, 82.2mg) was added slowly at 45 ℃ under argon and the reaction was continued for 30 minutes at 45 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (57.0mg, 71%, yellow solid).

The product detection data were as follows: ¹ H NMR(600MHz,CDCl ₃ ):δ7.42(s,1H),7.34-7.32(m,2H),7.27(d,J＝8.4Hz,2H),4.80(d,J＝5.4Hz,2H),2.58(s,3H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ201.4,134.7,134.2,129.8,129.2,49.8,34.3；HRMS(ESI)m/zcalculated for C ₉ H ₁₀ ClNS[M+H] ⁺ 200.0295,found 200.0293.MS(EI)m/z(％):201(16),199(40),142(8),140(28),127(33),125(100),89(26)；IR(KBr plate):3227,3065,2927,1596,1376,1336,1169,1092,927,814,695cm ^-1 .

example 17

Taking 4-bromobenzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 4-bromobenzyl bromide (0.4mmol, 100.0mg) was added slowly at 45 ℃ under an argon atmosphere and the reaction was continued at 45 ℃ for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (79.6mg, 82%, white solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.52(s,1H),7.49-7.45(m,2H),7.20(d,J＝8.4Hz,2H),4.77(d,J＝5.2Hz,2H),2.57(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ201.4,135.2,132.1,130.1,122.2,49.8,34.2；HRMS(ESI)m/zcalculated for C ₉ H ₁₀ BrNS[M+H] ⁺ 243.9790,245.9770,found 243.9801,245.9779.MS(EI)m/z(％):245(85),243(81),186(25),184(30),171(94),169(100)；IR(KBr plate):3216,3044,2924,1536,1487,1383,1332,1167,1072,1012,798cm ^-1 .

example 18

Taking 4-trifluoromethyl benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 4-trifluoromethyl benzyl bromide (0.4mmol, 95.6mg) was added slowly at 90 ℃ under argon and the reaction was continued for 30min at 90 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (11.6mg, 12%, yellow solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.60(d,J＝8.0Hz,2H),7.44(d,J＝8.0Hz,2H),4.90(d,J＝5.6Hz,2H),2.59(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ201.8,140.2,130.4(q,J＝33.0Hz),128.6,125.9(q,J＝4.0Hz),124.0(d,J＝270.0Hz).49.7,34.2；HRMS(ESI)m/z calculated for C ₁₀ H ₁₀ F ₃ NS[M+H] ⁺ 234.0559,found 234.0558.MS(EI)m/z(％):234(12),233(68),174(46),159(100),145(11)；IR(KBr plate):3222,3048,2928,1537,1387,1326,1166,1124,1067,1019,931,692cm ^-1 .

example 19

Taking 4-methylbenzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Argon shield4-methylbenzyl bromide (0.4mmol,74.0mg) was slowly added at room temperature (20 ℃ C.) and the reaction was continued at room temperature (20 ℃ C.) for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for guiding H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (55.3mg, 77%, yellow solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.46(s,1H),7,21(d,J＝7.8Hz,2H),7.16(d,J＝7.8Hz,2H),4.74(d,J＝5.4Hz,2H),2.55(s,3H),2.34(s,3H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ200.7,138.1,133.1,129.7,128.5,50.5,34.2,21.2；HRMS(ESI)m/z calculated for C ₁₀ H ₁₃ NS[M+H] ⁺ 180.0841,found 180.0839.MS(EI)m/z(％):179(31),120(19),105(100),91(17)；IR(KBr plate):3220,3049,3023,2922,1535,1385,1333,1166,1071,924,808,700cm ^-1 .

example 20

Taking 2-methylbenzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 2-methylbenzyl bromide (0.4mmol,74.0mg) was added slowly at room temperature (20 ℃ C.) under an argon blanket and the reaction was continued at room temperature (20 ℃ C.) for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is led into a reaction tube (the gas guide needle has obvious gas outflow) for 1 minute, tail gas is absorbed by copper sulfate aqueous solution, and the reaction tube continues to be used at the temperatureStirred for 20 minutes. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (58.5mg, 82%, yellow solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.28-7.18(m,5H),4.76(d,J＝4.8Hz,2H),2.55(s,3H),2.33(s,3H)； ¹³ CNMR(100MHz,CDCl ₃ ):δ200.6,137.1,134.1,130.9,129.6,128.6,126.5,49.1,34.1,19.2；HRMS(ESI)m/zcalculated for C ₁₀ H ₁₃ NS[M+H] ⁺ 180.0841,found 180.0850.MS(EI)m/z(％):179(83),164(9),105(100),91(18)；IR(KBr plate):3218,3021,2924,1531,1389,1331,1169,1071,924,745cm ^-1 .

example 21

3-methyl benzyl bromide and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 3-methylbenzyl bromide (0.4mmol,74.0mg) was added slowly at room temperature (20 ℃) under an argon blanket and the reaction was continued at room temperature (20 ℃) for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (51.5mg, 72%, oily liquid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.44(s,1H),7.27-7.24(m,1H),7.15-7.11(m,3H),4.76(d,J＝5.2Hz,2H),2.57(s,3H),2.35(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ200.8,138.9,136.0,129.2,190.0,128.95,125.5,50.8,34.2,21.5；HRMS(ESI)m/z calculated for C ₁₀ H ₁₃ NS[M+H] ⁺ 180.0841,found 180.0850.MS(EI)m/z(％):179(86),146(36),120(28),105(100),91(12)；IR(KBr plate):3220,3026,2921,1534,1491,1331,1168,1072,942,693cm ^-1 .

example 22

Taking 4-tert-butyl benzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 4-tert-butylbenzylbromide (0.4mmol, 90.9mg) was slowly added at room temperature (20 ℃) under argon protection, and the reaction was continued at room temperature (20 ℃) for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas introduction needle with significant gas outflow) for 1 minute, the tail gas is absorbed with aqueous copper sulfate solution and stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (74.6mg, 84%, white solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.40(d,J＝8.4H z,2H),7.27(d,J＝8.4Hz,2H),4.76(d,J＝4.8Hz,2H),2.56(s,3H),1.32(s,9H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ200.7,151.5,133.1,128.4,126.0,50.5,34.7,34.2,31.4；HRMS(ESI)m/z calculated for C ₁₃ H ₁₉ NS[M+H] ⁺ 222.1311,found 222.1320.MS(EI)m/z(％):221(78),162(19),147(100),132(52),117(29)；IR(KBr plate):3217,2962,1536,1388,1333,1166,1071,1019,927,690cm ^-1 .

example 23

3-methoxybenzyl bromide and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 3-methoxybenzyl bromide (0.4mmol, 80.4mg) was added slowly at room temperature (20 ℃) under argon protection, and the reaction was continued at room temperature (20 ℃) for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (13.0mg, 17%, yellow oily liquid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.41(s,1H),7.30-7.27(m,1H),6.92-6.85(m,3H),4.77(d,J＝5.2Hz,2H),3.81(s,3H),2.58(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ200.9,160.0,137.6,130.1,120.6,114.1,113.6,55.4,50.7,34.2；HRMS(ESI)m/z calculated for C ₁₀ H ₁₃ NOS[M+H] ⁺ 196.0791,found 196.0799.MS(EI)m/z(％):195(73),162(45),136(20),122(12),121(100)；IR(KBr plate):3221,3049,2933,1601,1534,1490,1331,1292,1166,1047,785,691cm ^-1 .

example 24

Taking 2-bromomethylnaphthalene and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 2-bromomethylnaphthalene (0.4mmol, 88.4mg) was added slowly at 0 deg.C under argon blanket and the reaction was continued for 30 minutes in an ice-water bath (0 deg.C). Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, diatomite is used for filtering to remove solid impurities such as elemental sulfur and the like, and ethyl acetate is used as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (56.7mg, 66%, yellow solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.85-7.81(m,3H),7.76(s,1H),7.51-7.48(m,2H),7.42(dd,J＝1.6Hz,J＝8.4Hz,1H),4.96(d,J＝5.2Hz,2H),2.59(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ201.0,133.5,133.4,133.1,128.9,127.9,127.8,127.4,126.6,126.4,126.1,50.8,34.2；HRMS(ESI)m/z calculated for C ₁₃ H ₁₃ NS[M+H] ⁺ 216.0841,found 216.0842.MS(EI)m/z(％):215(33),182(25),156(9),141(100),127(8)；IR(KBr plate):3360,3219,3051,2923,1531,1392,1362,1323,1167,1074,1019,818,741cm ^-1

example 25

3, 5-di-tert-butyl benzyl bromide and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 3, 5-di-tert-butylbenzylbromide (0.4mmol, 113.3mg) was slowly added at room temperature (20 ℃) under an argon blanket, and the reaction was continued at room temperature (20 ℃) for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas introduction needle with significant gas outflow) for 1 minute, the tail gas is absorbed with aqueous copper sulfate solution and stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (90.9mg, 82%, white solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.47(s,1H),7.42(s,1H),7.19(d,J＝1.8Hz,2H),4.76(d,J＝4.8Hz,2H),2.57(s,3H),1.34(s,18H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ200.4,151.7,135.2,123.0,122.5,51.7,35.0,34.1,31.5；HRMS(ESI)m/z calculated for C ₁₇ H ₂₇ NS[M+Na] ⁺ 300.1756,found 300.1768.MS(EI)m/z(％):278(20),277(100),262(7),203(95),187(31),57(43)；IR(KBr plate):3238,3055,2964,2866,1599,1545,1390,1363,1172,1077,945,712cm ^-1 .

example 26

Taking 4-fluoro-2-methylbenzyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Under the protection of argon, at room temperature4-fluoro-2-methylbenzyl bromide (0.4mmol, 81.2mg) was added slowly (20 ℃ C.) and the reaction was continued at room temperature (20 ℃ C.) for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (67.3mg, 85%, white solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.45(s,1H),7.19(dd,J＝6.0Hz,J＝8.4Hz,1H),6.90-6.83(m,2H),4.69(d,J＝4.8Hz,2H),2.52(s,3H),2.29(s,3H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ200.7,162.5(d,J＝244.5),139.5(d,J＝7.5Hz),131.1(d,J＝9.0Hz),129.8(d,J＝3.0Hz),117.5(d,J＝21.0Hz),113.0(d,J＝21.0Hz),48.2,33.9,19.3；HRMS(ESI)m/z calculated for C ₁₀ H ₁₂ FNS[M+H] ⁺ 198.0747,found 198.0746.MS(EI)m/z(％):198(6),197(48),138(10),123(100),122(57),109(11)；IR(KBr plate):3217,3033,2984,2925,1532,1500,1388,1329,1254,1170,1068,1005,961,699cm ^-1 .

example 27

4-chloro-2-fluorobenzyl bromide and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Under argon, 4-chloro-2-fluorobenzyl bromide (0.4mmol,89.4mg) was added slowly at 90 ℃ and the reaction was continued for 30 minutes at 90 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S introductionIn the reaction tube (gas was apparently vented through the gas-conducting needle) for 1 minute, the tail gas was absorbed with aqueous copper sulfate solution and stirring was continued at this temperature for 20 minutes. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (44.2mg, 51%, yellow solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.64(s,1H),7.35(t,J＝8.4Hz,1H),7.10(t,J＝7.8Hz,2H),4.84(d,J＝5.4Hz,2H),2.55(s,3H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ201.6,160.9(d,J＝247.5Hz),135.0(d,J＝10.5Hz),131.8(d,J＝4.5Hz),124.8(d,J＝3.0Hz),121.9(d,J＝15.0Hz),116.5(d,J＝24.0Hz),43.6(d,J＝1.5Hz),34.2；HRMS(ESI)m/z calculated for C ₉ H ₉ ClFNS[M+H] ⁺ 218.0201,found 218.0200.MS(EI)m/z(％):219(15),217(39),160(11),158(36),145(22),143(100)；IR(KBr plate):3220,3048,2932,1612,1535,1489,1336,1170,1078,931,896,687cm ^-1 .

example 28

Taking (1-bromoethyl) benzene and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Under argon, (1-bromoethyl) benzene (0.4mmol,74.0mg) was added slowly at 0 ℃ and the reaction was continued for 30 minutes in an ice-water bath (0 ℃). Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, diatomite is used for filtering to remove elemental sulfur and other solidsBulk impurities, ethyl acetate was used as eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (52.9mg, 74%, yellow oily liquid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.54(s,1H),7.38-7.34(m,4H),7.32-7.28(m,1H),5.76-5.71(m,1H),2.53(s,3H),1.60(d,J＝7.2Hz,3H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ199.6,141.3,128.9,128.0,126.7,54.9,34.5,20.0；MS(EI)m/z(％):179(44),146(61),120(11),105(100),104(58),77(28)；IR(KBr plate):3219.3030,2974,1531,1453,1385,1217,1181,1091,761,698cm ^-1 .

example 29

1-bromo-4- (1-bromoethyl) benzene and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 1-bromo-4- (1-bromoethyl) benzene (0.4mmol,105.6mg) was added slowly at 0 deg.C under argon protection and the reaction was continued for 30 minutes in an ice-water bath (0 deg.C). Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas introduction needle with significant gas outflow) for 1 minute, the tail gas is absorbed with aqueous copper sulfate solution and stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (81.3mg, 79%, yellow solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.79(s,1H),7.43(d,J＝8.4Hz,2H),7.20(d,J＝8.4Hz,2H),5.67-5.60(m,1H),2.49(s,3H),1.54(d,J＝6.8Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ199.9,140.3,131.8,128.3,121.6,54.3,34.2,20.3；HRMS(ESI)m/z calculated for C ₁₀ H ₁₂ BrNS[M+H] ⁺ 257.9947,259.9926,found 257.9946,269.9925.MS(EI)m/z(％):259(37),257(33),185(42),184(34),183(43),182(32),104(100)；IR(KBr plate):3217,3028,2975,2928,1530,1489,1455,1383,1218,1094,1073,1009,826,728cm ^-1 .

example 30

Diphenyl bromomethane and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Under argon, diphenylbromomethane (0.4mmol,98.9mg) was added slowly at-35 ℃ and the reaction was continued at-35 ℃ for 30 minutes. Continuing to maintain the temperature, introducing H through a gas-conducting needle ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (44.5mg, 46%, white solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.80(s,1H),7.37-7.27(m,6H),7.24-7.21(m,4H),6.84(d,J＝8.0Hz,1H),2.56(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ200.4,139.9,128.9,127.9,127.8,63.1,34.3；HRMS(ESI)m/zcalculated for C ₁₅ H ₁₅ NS[M+Na] ⁺ 264.08171,found 264.0817.MS(EI)m/z(％):241(40),208(32),167(100),164(9),152(33)；IR(KBr plate):3219,3060,2915,1520,1376,1173,1084,1061,744,698cm ^-1 .

example 31

Taking tert-butyl bromide and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Under argon, t-butyl bromide (0.4mmol, 54.8mg) was added at-35 ℃ and the reaction was continued for 30 minutes at-35 ℃. Continuing to maintain the temperature, introducing H through a gas-conducting needle ₂ S is introduced into the reaction tube (gas introduction needle with significant gas outflow) for 1 minute, the tail gas is absorbed with aqueous copper sulfate solution and stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (11.9mg, 23%, white solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.02(s,1H),2.51(s,3H),1.55(s,9H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ199.9,56.0,37.6,27.8；MS(EI)m/z(％):131(100)；IR(KBr plate):3231,3046,2966,2928,1540,1363,1140,1021,738,703cm ^-1 .

example 32

Taking bromocyclopentane and acetonitrile as raw materials:

drying the dried 10mL reaction tubeThe reagent (2) is put into a glove box, and NO is added ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Bromocyclopentane (0.4mmol,59.6mg) was added slowly at 45 ℃ under argon protection and the reaction was continued for 30min at 45 ℃. The temperature is adjusted to-15 ℃, and H is injected by using a gas guide needle ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, diatomite is used for filtering to remove solid impurities such as elemental sulfur and the like, and ethyl acetate is used as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (36.1mg, 63%, yellow solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.42(s,1H),4.71-4.65(m,1H),2.50(s,3H),2.13-2.08(m,2H),1.72-1.66(m,2H),1.65-1.60(m,2H),1.51-1.46(m,2H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ199.8,57.7,34.5,32.2,24.1；HRMS(ESI)m/z calculated for C ₇ H ₁₃ NS[M+Na] ⁺ 166.0661,found 166.0660.MS(EI)m/z(％):143(100),84(9),76(68),69(7),59(24)；IR(KBr plate):3225,3036,2960,2869,1536,1456.1390,1346,1143,1095,723cm ^-1 .

example 33

Bromo-cycloheptane and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Bromocycloheptane (0.4mmol,70.8mg) was added slowly at 45 deg.C under argon and the reaction was continued for 30min at 45 deg.C. The temperature is adjusted to-15 ℃, and the use guide is usedAir needle is used for driving H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (36.1mg, 63%, yellow solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.50(s,1H),4.44-4.41(m,1H),2.48(s,3H),2.03-1.99(m,2H),1.63-1.57(m.4H),1.52-1.47(m,6H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ198.4,56.9,34.5,33.6,28.0,24.2；HRMS(ESI)m/zcalculated for C ₉ H ₁₁ NS[M+H] ⁺ 172.1154,found 172.1154.MS(EI)m/z(％):171(54),138(100),112(56)；IR(KBr plate):3221,3036,2928,2855,1534,1461,1391,1368,1155,1069,715cm ^-1 .

example 34

Taking 7-bromonorbornane and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 7-bromonorbornane (0.4mmol,70.0mg) was added slowly at 45 ℃ under argon and the reaction was continued for 30 minutes at 45 ℃. Cooling to-15 deg.C, and introducing H with air-guiding needle ₂ S is introduced into the reaction tube (the gas guide needle has obvious gas outflow) for 1 minute, the tail gas is absorbed by the copper sulfate aqueous solution, and the stirring is continued for 20 minutes at the temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. Then distilling the filtrate under reduced pressure to remove organic solvent, and subjecting the crude product to silica gel flash column chromatographyPurification (petroleum ether/ethyl acetate) gave the corresponding product (51.9mg, 77%, white solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.33(s,1H),4.14(d,J＝7.8Hz,J＝10.8Hz,2H),2.49(s,3H),2.37(d,J＝3.6Hz,1H),2.31(s,1H),1.90-1.86(m,1H),1.54-1.44(m,2H),1.34-1.23(m,4H),1.16-1.12(m,1H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ199.2,59.4,41.6,39.8,36.2,35.9,34.4,28.1,26.5；HRMS(ESI)m/z calculated for C ₉ H ₁₅ NS[M+H] ⁺ 170.0998,found 170.0996.MS(EI)m/z(％):169(100),136(38),113(67),110(11),95(30)；IR(KBr plate):3214,3039,2956,2873,1537,1454,1370,1347,1304,1137,1096,718cm ^-1 .

example 35

1-bromoadamantane and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 1-bromoadamantane (0.4mmol,86.1mg) was added slowly at 45 ℃ under argon protection and the reaction was continued for 30 minutes at 45 ℃. Cooling to-35 deg.C, and introducing H with air-guiding needle ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (55.2mg, 66%, white solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ6.92(s,1H),2.49(s,3H),2.28(d,J＝1.6Hz,6H),2.10(s,3H),1.68(s,6H)；

¹³ C NMR(100MHz,CDCl ₃ ):δ199.3,56.7,40.1,37.8,36.3,29.5；MS(EI)m/z(％):209(55),208(64),194(8),150(3),135(100)；IR(KBr plate):3308,2908,2895,1525,1406,1393,1090,670,639cm ^-1 .

example 36

Taking benzyl bromide and n-butyronitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) and n-butyronitrile (2.0mmol, 138.2mg) were dissolved in 1mL of dry CH ₃ NO ₂ In (1). The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon blanket and the reaction was continued for 30min at 45 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (44.2mg, 57%, oily liquid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.41(s,1H),7.38-7.35(m,2H),7.33-7.31(m,3H),4.82(d,J＝4.8Hz,2H),2.64(t,J＝7.2Hz,2H),1.85-1.79(m,2H),0.95(t.J＝7.8Hz,3H)； ¹³ C NMR(150MHz,CDCl ₃ ):δ205.6,136.3,129.1,128.4,128.2,50.4,49.1,22.9,13.5；HRMS(ESI)m/z calculated for C ₁₁ H ₁₅ NS[M+H] ⁺ 194.0998,found 194.0997.MS(EI)m/z(％):193(100),149(53),123(59),106(59)；IR(KBr plate):3226,3032,2962,2931,2872,1532,1454,1404,1167,1075,1027,738,697\cm ^-1 .

example 37

Taking benzyl bromide and cyclopentanenitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) and cyclopentanenitrile (2.0mmol, 190.3mg) are dissolved in 1mL dry CH ₃ NO ₂ In (1). The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon blanket and the reaction was continued for 30min at 45 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (44.4mg, 51%, yellow solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.39-7.31(m,5H),4.84(d,J＝5.2Hz,2H),2.94-2.86(m,1H),2.00-1.93(m,4H),1.87-1.77(m,2H),1.66-1.55(m,2H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ210.2,136.5,129.1,128.4,128.2,55.3,50.3,34.2,25.9；HRMS(ESI)m/z calculated for C ₁₃ H ₁₇ NS[M+H] ⁺ 220.1154,found 220.1153.MS(EI)m/z(％):219(100),149(30),113(19),106(60)；IR(KBr plate):3237,3031,2955,2867,1527,1451,1402,1321,1131,1076,1028,732,696,617cm ^-1 .

example 38

Taking benzyl bromide and benzonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) and benzonitrile (2.0mmol, 206.2mg) in 1mL of dry CH ₃ NO ₂ In (1). The reaction tube was sealed with a sealing film and removed from the glove box. Benzyl bromide (0.4mmol, 68.4mg) was added dropwise at 45 ℃ under an argon blanket and the reaction was continued for 30min at 45 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (19.4mg, 21%, yellow solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.76-7.74(m,3H),7.48-7.44(m,1H),7.41-7.35(m,7H),5.00(d,J＝5.2Hz,2H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ199.3,141.8,136.3,131.3,129.2,128.7,128.5,128.4,126.8,51.2；HRMS(ESI)m/z calculated for C ₁₄ H ₁₃ NS[M+H] ⁺ 220.0841,found 220.0841.MS(EI)m/z(％):227(91),149(10),121(100),106(69)；IR(KBr plate):3232,3060,3029,1519,1450,1381,1335,1066,1029,943,694cm ^-1 .

example 39

Taking 7-bromonorbornane and n-butyronitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) and n-butyronitrile (2.0mmol, 138.2mg) were dissolved in 1mL of dry CH ₃ NO ₂ In (1). The reaction tube was sealed with a sealing film and removed from the glove box. 7-bromonorbornane (0.4mmol,70.0mg) was added at 45 ℃ under an argon blanket and the reaction was continued for 30 minutes at 45 ℃. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (55.3mg, 70%, white solid).

The product detection data were as follows:

¹ H NMR(600MHz,CDCl ₃ ):δ7.20(s,1H),4.18-4.15(m,1H),2.55(t,J＝7.8Hz,2H),2.37(d,J＝3.6Hz,1H),2.31(s,1H),1.91-1.87(m,1H),1.77-1.74(m,2H),1.53-1.46(m,2H),1.33-1.23(m,4H),1.16-1.13(m,1H),0.91(t,J＝7.2Hz,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ203.8,59.0,49.2,41.6,40.0,36.2,35.9,28.1,26.5,22.9,13.3；

example 40

Taking 7-bromonorbornane and cyclohexanecarbonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) and cyclohexanecarbonitrile (2.0mmol, 218.3mg) in 1mL dry CH ₃ NO ₂ In (1). The reaction tube was sealed with a sealing film and removed from the glove box. 7-bromonorbornane (0.4mmol,70.0mg) was added at 45 ℃ under argon and the reaction was continued at 45 ℃ for 30 minutes. Then the temperature is reduced to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube(significant gas flow through the gas needle) for 1 minute, the tail gas was absorbed using aqueous copper sulfate solution and stirring was continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (61.7mg, 65%, white solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):7.02(s,1H),4.23-4.18(m,1H),2.45-2.33(m,3H),1.95-1.78(m,5H),1.69-1.67(m,1H),1.61-1.45(m,4H),1.33-1.14(m,8H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ208.6,58.5,55.1,41.7,40.2,36.3,36.0,33.04,32.95,28.2,26.5,26.1,25.7；

EXAMPLE 41

1-bromo-3, 5-dimethyladamantane and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. 1-bromo-3, 5-dimethyladamantane (0.4mmol,97.3mg) was added slowly at 45 ℃ under argon and the reaction was continued for 30 minutes at 45 ℃. Cooling to-35 deg.C, and introducing H with air-guiding needle ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (67.9mg, 72%, yellow oily liquid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ6.99(s,1H),2.46(s,3H),2.16-2.13(m,1H),2.12(s,2H),1.90(dd,J＝12.4Hz,J＝28.4Hz,4H),1.38-1.25(m,4H),1.18-1.10(m,2H),0.83(s,6H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ199.3,58.3,50.6,45.9,42.6,38.5,37.7,32.6,30.1,30.0；HRMS(ESI)m/z calculated for C ₁₄ H ₂₃ NS[M+H] ⁺ 238.1624,found 238.1623.MS(EI)m/z(％):237(30),236(40),213(16),163(58),107(100)；IR(KBr plate):3253,3037,2945,2903,2862,2842,1535,1454,1393,1161,1069,1040,690cm ^-1 .

example 42

The salix musk bromo-derivative and acetonitrile are used as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Salix musk bromo-derivative (0.4mmol,123.7mg) was added at-35 ℃ under argon protection and the reaction was continued at-35 ℃ for 30 min. Continuing to maintain the temperature, introducing H through a gas-conducting needle ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent, and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (61.8mg, 51%, white solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ7.21(d,J＝1.6Hz,1H),7.16(d,J＝1.6Hz,1H),5.81-5.74(m,1H),2.86(td,J＝2.8Hz,J＝7.2Hz,2H),2.53(s,3H),1.93(t,J＝7.2Hz,2H),1.62(d,J＝6.8Hz,3H),1.35(s,9H),1.27(s,3H),1.26(s,3H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ199.0,153.5,150.7,139.3,135.8,120.2,118.9,53.2,44.3,41.4,35.1,34.6,31.8,28.9,28.8,28.4,18.5；HRMS(ESI)m/z calculated for C ₁₉ H ₂₉ NS[M+H] ⁺ 304.2093,found304.2092.MS(EI)m/z(％):303(9),229(88),228(100),213(91),129(43),115(29)；IR(KBr plate):3217,2955,2864,1531,1458,1384,1103,1042,748,720cm ^-1 .

example 43

The method is characterized by taking ezetimibe bromo-derivative and acetonitrile as raw materials:

putting the dried 10mL reaction tube and the dried reagent into a glove box, and adding NO ₂ BF ₄ (0.6mmol,79.7mg) was dissolved in 1mL of extra dry acetonitrile. The reaction tube was sealed with a sealing film and removed from the glove box. Ezetimibe bromo-derivative (0.4mmol,206.9mg) was added slowly at-35 ℃ under argon protection and the reaction was continued for 30min at-35 ℃. The temperature is raised to-15 ℃, and a gas guide needle is used for leading H ₂ S is introduced into the reaction tube (gas is apparently released from the gas-conducting needle) for 1 minute, the tail gas is absorbed by the aqueous copper sulfate solution, and the stirring is continued for 20 minutes at this temperature. After the reaction is finished, filtering the mixture by using kieselguhr to remove solid impurities such as elemental sulfur and the like, and using ethyl acetate as an eluent. The filtrate was then distilled under reduced pressure to remove the organic solvent and the crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product (105.0mg, 52%, yellow solid).

The product detection data were as follows:

¹ H NMR(400MHz,CDCl ₃ ):δ8.30(d,J＝8.0Hz,1H),8.21(d,J＝8.4Hz,0.9H),7.34-7.27(m,8H),7.22-7.17(m,4H),7.10(s,2H),7.08(s,1.8H),7.02-6.98(m,4H),6.94-6.89(m,4H),5.64(q,J＝8.0Hz,0.9H),5.54(q,J＝7.6Hz,1H),4.65(d,J＝2.0Hz,0.9H),4.63(d,J＝2.0Hz,1H),3.08-3.04(m,2H),2.48(s,3H),2.45(s,2.8H),2.30(s,3H),2.29(s,2.7H),2.24-1.76(m,8H)； ¹³ C NMR(100MHz,CDCl ₃ ):δ200.5,200.2,169.6,169.5,167.2,167.1,163.51,163.46,161.1,161.0,160.4,157.9,150.9,135.88,135.85,135.5,135.4,134.8,134.7,133.5,129.0,128.9,128.8,128.7,127.0,122.62,122.59,118.54,118.46,116.1,115.92,115.87,115.71,115.65,60.9,60.6,60.2,60.1,58.9,58.6,34.1,32.5,32.1,25.58,25.55,21.1；HRMS(ESI)m/z calculated for C ₂₈ H ₂₆ F ₂ N ₂ O ₃ S[M+Na] ⁺ 531.1524,found 531.1523.MS(EI)m/z(％):509(11),508(36),474(19),296(16),254(96),194(51),135(100)；IR(KBr plate):3302,3047,2985,2936,1743,1510,1372,1223,1045,1015,836cm ^-1 .

finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The method for synthesizing thioamide is characterized by comprising the following steps of:

(3) cooling to-35-45 ℃, and adding a vulcanizing agent for reaction;

Wherein R is various substituted benzyl, linear alkyl and cycloalkyl, R ¹ Is alkyl or phenyl;

2. The method of claim 1, wherein the nitronium salt of step (1) is NOBF ₄ 、NO ₂ BF ₄ 、NOPF ₆ And NOSbF ₆ The nitrile compound is one of acetonitrile, n-butyronitrile, cyclopentanenitrile, benzonitrile and cyclohexanenitrile.

3. The method of claim 1, wherein the nitronium salt and the nitrile compound of step (1) are added in an amount of 0.6: 1 n/v; the addition amount of the nitronium salt, the nitrile compound and the solvent is 6: 20: 10 n/n/v.

4. The method of claim 1, wherein the solvent of step (1) is CH ₃ CN or CH ₃ NO ₂ 。

5. The method of claim 1, wherein the bromide in step (2) is benzyl bromide, 4-fluorobenzyl bromide, 2-fluorobenzyl bromide, 3-fluorobenzyl bromide, 4-chlorobenzyl bromide, 4-bromobenzyl bromide, 4-trifluoromethylbenzyl bromide, 4-methylbenzyl bromide, 2-methylbenzyl bromide, 3-methylbenzyl bromide, 4-tert-butylbenzyl bromide, 3-methoxybenzyl bromide, 2-bromomethylnaphthalene, 3, 5-di-tert-butylbenzyl bromide, 4-fluoro-2-methylbenzyl bromide, 4-chloro-2-fluorobenzyl bromide, (1-bromoethyl) benzene, 1-bromo-4- (1-bromoethyl) benzene, diphenylbromomethane, tert-butylbromide, bromocyclopentane, bromocycloheptane, 7-bromonorbornane, or a mixture thereof, Any one of 1-bromoadamantane, 7-bromonorbornane, 1-bromo-3, 5-dimethyladamantane, salidroside bromo-derivative and ezetimibe bromo-derivative.

6. The method of claim 1, wherein the reaction time of step (2) is 30 min.

7. The method of synthesis according to claim 1, wherein the molar ratio of bromide to nitronium salt is 1: 1.5.

8. The method of claim 1, wherein the sulfurizing reagent of step (3) is thioacetamide, thiourea, Na ₂ S, NaHS or H ₂ S。

9. The synthesis method of claim 1, wherein the solid impurities in step (4) are removed by filtration with celite, using ethyl acetate as eluent; distilling the filtrate under reduced pressure to remove the organic solvent; the crude product was purified by flash column chromatography on silica gel.

10. The method of claim 1, wherein said thioamide comprises