WO2015113192A1

WO2015113192A1 - Benzo-lactam compound, synthesis method and application thereof

Info

Publication number: WO2015113192A1
Application number: PCT/CN2014/071616
Authority: WO
Inventors: 王君良; 蔡国平; 江海; 陈邦池
Original assignee: 迈克斯(如东)化工有限公司; 浙江省诸暨合力化学对外贸易有限公司
Priority date: 2014-01-28
Filing date: 2014-01-28
Publication date: 2015-08-06

Abstract

Disclosed are a benzo-lactam compound, a synthesis method and an application thereof, which comprises the following steps: step (a): compound (I) and compound (II) or compound (III) reacting with an action of a catalyst or without the action of the catalyst and in a condition with a solvent or without the solvent to obtain compound (IV); and step (b): compound (IV) and compound (V) reacting in presence of an acid binding agent and a phase transfer catalyst to obtain component (VI). For a general formula of benzo-lactam compound (VI), see formula I. The method is not only mild in a condition, easy to control in a process, simple in after-treatment, but also capable of obtaining the benzo-lactam compound with a high yield and high purity. The obtained benzo-lactam compound can be further used for synthesizing flumioxazin or other benzo-lactam compounds provided with various wide biological organic and pharmacological activity.

Description

Benzolactam compound and synthesis method and application thereof

Technical field

The invention relates to the technical field of synthesis and application of benzoheterocyclic compounds, in particular to benzolactam compounds and methods and applications thereof.

Background technique

The benzolactam compound itself is a class of compounds having a wide range of bioorganic and pharmaceutical activities or important synthetic intermediates. Propionamide is one of the most representative members. Propionamide is a herbicide that is absorbed by young shoots and leaves. Soil treatment can effectively prevent annual broadleaf weeds and some grass weeds. Propifluramide is easily degraded in the environment and is safe for later crops.

A method for the synthesis of propifluramide is disclosed in US Pat. No. 4,640,707, US Pat. No. 4,792, 605, US Pat. The key step of the method is to react 6-amino-7-fluoro-2H-M-benzoxazine-3(4H)-one with a halogenated propyne under strong alkali to obtain 4-N-propyl. Alkylation product. However, due to the presence of a 6-primary amine group in the structure of the substrate, the propargylation is not chemically selective and produces polypropargylation by-products. This not only wastes expensive intermediates and propargylating agents, but also the purification of impure products leads to an increase in overall process costs.

Another method for synthesizing propiflufloxacin is disclosed in JP 5097826A. This method protects the 6 primary amines in 6-amino-7-fluoro-2H-1,4-benzoxazine-3(4H)-one with mercapto ketone. This method uses both a large amount of decyl ketone as a protective reagent and a solvent. The reaction was refluxed under reduced pressure for several hours. The resulting protected intermediate is then propargylated to give the 4-N-propyne-6-imine intermediate. This method requires not only a large amount of mercapto ketone but also an intermediate of 4-N-propyne-6-imine which is an oily liquid which is difficult to refine and which makes it difficult to synthesize the final high-purity propiflufen product.

Summary of the invention

It is an object of the present invention to overcome the deficiencies of the prior art and to provide benzolactam compounds and methods for their synthesis and use. Benzolactam compound (VI)

In the formula:

RH, d_ ₅ embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl group, ₍₆ _ ₁₂ aryl;

Is CM alkyl with, C ₃ _ ₇ cycloalkyl embankment group, C ₆ _ ₁₂ aryl group, d_ ₅ amino embankment, d_ ₅ embankment group, d_ ₅ embankment mercapto; to 15, CM alkyl with, CF _3, CN; X is 0, s;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1.

Said is 15 or propynyl; is p-nitrophenyl or p-chlorophenyl; R ₃ is H or methyl; X is 0; Y is H or F; n is 0.

The steps of the preparation method of the benzolactam compound are as follows:

Step (a): Compound (I) is reacted with compound (II) or compound (III) in the presence or absence of a catalyst in the presence or absence of a solvent to obtain compound (IV).

Step (b): Compound (IV) is reacted with compound (V) in the presence of an acid binding agent and a phase transfer catalyst to obtain compound (VI). The compound (I) has the formula:

In the formula:

Is 15, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

X is 0, S;

丫 is d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of compound (II) is:

Ύ ( ) where:

It is CM alkyl with, C ₃ _ ₇ cycloalkyl embankment group, C ₆ _ ₁₂ aryl group, d_ ₅ amino embankment, d_ ₅ embankment group, d_ ₅ embankment mercapto; compounds of general formula (III) are:

In the formula:

X is 0, S;

CM thiol, ( ₆ _ ₁₂ aryl;

Z is d_ ₅ fluorenyl, C ₆ _{-12 12} aryl, d ₅垸 amino, d ₅ methoxy, d ₅ fluorenyl; The formula of the compound (IV) is:

In the formula:

Is CM alkyl with, C ₃ _ ₇ cycloalkyl embankment group, C ₆ _ ₁₂ aryl group, d_ ₅ embankment amino, d_ ₅ embankment group, d_ ₅ embankment mercapto; to 15, d_ ₅ embankment, halogen, CF _3, CN ;

X is 0, S;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of the compound (V) is:

(V)

In the formula:

! ^为为. ^ Embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl group, ₍₆ _ ₁₂ aryl;

It is a halogen, a sulfonate, a sulfate or a phosphate.

The compound (II) described in the step (a) is p-nitrobenzaldehyde, p-chlorobenzaldehyde or hydrazine, hydrazine-dimethylformamide, and the compound (III) is trimethyl orthoformate or triethyl orthoformate. The catalyst is a dehydrating agent or an acid, and the dehydrating agent is preferably a molecular sieve, anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous calcium chloride or thionyl chloride; the acid is preferably sulfuric acid, hydrochloric acid, acetic acid, Phosphoric acid or p-toluenesulfonic acid; the solvent is an organic solvent, and the organic solvent is preferably toluene, xylene, methanol, ethanol, isopropanol or anthracene, fluorenyl-dimercaptocarboxamide.

The compound (V) described in the step (b) is chloropropyne, bromopropyne or propyne methanesulfonate, the acid binding agent is an inorganic base or an organic base; and the inorganic base is preferably potassium carbonate or sodium carbonate. , sodium hydrogencarbonate, sodium hydroxide or potassium hydroxide; the organic base is preferably piperidine, pyridine or triethylamine, the phase transfer catalyst is a quaternary ammonium salt, a quaternary phosphonium salt or a crown ether, the quaternary ammonium salt Preferably, it is tetrabutylammonium bromide, triethylphenylammonium chloride or tetrabutylammonium hydrogen sulfate, and the quaternary phosphonium salt is preferably hexadecanoyltributylphosphonium bromide or n-butyltri-n-octane The guanidine bromide, the crown ether is preferably 18-crown-6.

The use of the benzolactam compound is for the preparation of the compound (VIII), and the compound (VIII) has the following formula:

Where Q represents:

In the formula:

Is 15, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

R ₇ is H, d_ ₅ embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl, C ₃ _ ₇ cycloalkyl embankment group, C ₆ _ ₁₂ aryl;

, R ₉ is selected from H, d_ ₅ embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl, C ₃ _ ₇ cycloalkyl embankment group, C ₆ _ ₁₂ aryl group or combined together as trimethylene, tetramethylene, Methylene or pentamethylene ring;

X is 0, S;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1;

m is 1-4.

The steps of the preparation method of the compound (VIII) are as follows:

Step (a) Compound (VI) gives compound (VII) under the action of a catalyst,

Step (b) Compound (VII) is reacted with compound (IX), compound (X), compound (XI) or compound (XII) in an organic solvent to obtain a compound (νπι;>,

The general formula of the compound (VI) is as follows:

In the formula:

X is 0, S;

Y is H, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of the compound (VII) is as follows:

In the formula:

! ^^ ^ is alkyl, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl, C ₆ _ ₁₂ aryl;

Is 15, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

X is 0, S;

Y is H, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of the compound (IX) is as follows:

o

R people ( ^IX )

In the formula:

R ₇ is H, d_ ₅ embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl, C ₃ _ ₇ cycloalkyl group embankment, C,

L ₂ is halogen, hydroxy, carbonyloxy;

The general formula of the compound (X) is as follows:

In the formula:

m is 1-4;

The general formula of the compound (XI) is as follows:

In the formula:

, R ₉ is selected from H, d_ ₅ embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl, C ₃ _ ₇ cycloalkyl, C ₆ _ ₁₂ aryl group or combined together as trimethylene, tetramethylene, Methylene or pentamethylene ring;

The general formula of the compound (XII) is as follows:

The catalyst described in the step (a) is an acid or a base, and the acid is preferably one or more of sulfuric acid, hydrochloric acid, acetic acid, phosphoric acid, p-toluenesulfonic acid or zinc chloride; the base is preferably hydrogen. One or more of sodium oxide, potassium hydroxide, ethanolamine, hydrazine hydrate, piperidine, aqueous ammonia, ethylamine, n-propylamine or n-hexylamine. In the step (b), the organic solvent is preferably xylene or chlorine. One or more of benzene, toluene, methylene chloride, trichloromethane or acetic acid.

The method is not only mild in condition, the process is easy to control, the post-treatment is simple, and the benzolactam compound can be obtained in high yield and high purity. The resulting benzolactam compound can be further used for the synthesis of propiflufenic or other benzolactam compounds having a wide variety of bioorganic and pharmaceutical activities.

detailed description

The benzolactam compound (VI) has the following formula:

In the formula:

Is CM alkyl with, C ₃ _ ₇ cycloalkyl embankment group, C ₆ _ ₁₂ aryl group, d_ ₅ amino embankment, d_ ₅ embankment group, d_ ₅ embankment mercapto; to 15, CM alkyl with, CF _3, CN;

X is 0, S;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1.

Said 15 or propynyl; p-nitrophenyl or p-chlorophenyl; 15 or methyl; X is 0; Y is H or F; n is 0.

The steps of the preparation method of the benzolactam compound are as follows:

In the formula:

For d_ ₅ fluorenyl, halogen, CF ₃ , CN;

X is 0, s;

丫 is d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of compound (II) is:

Ύ ( ) where:

In the formula:

X is 0, S;

CM thiol, ( ₆ _ ₁₂ aryl;

Z is d_ ₅ fluorenyl, C ₆ _{-12 12} aryl, d ₅垸 amino, d ₅ methoxy, d ₅ fluorenyl;

The formula of the compound (IV) is:

In the formula:

X is 0, S;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1; The general formula of the compound (V) is:

(ν)

In the formula:

It is a halogen, a sulfonate, a sulfate or a phosphate.

Where Q represents:

In the formula:

Is 15, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

, R ₉ is selected from H, d_ ₅ embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl, C ₃ _ ₇ cycloalkyl embankment group, C ₆ _ ₁₂ aryl group or combined together as trimethylene, tetramethylene, Methylene or pentamethylene ring; X is 0, s;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1;

m is 1-4.

The steps of the preparation method of the compound (VIII) are as follows:

Step (a) Compound (VI) gives compound (VII) under the action of a catalyst,

The general formula of the compound (VI) is as follows:

In the formula:

X is 0, S;

Y is H, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of the compound (VII) is as follows:

In the formula:

! ^为为. ^ Embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl, C,

Is 15, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

X is 0, S;

Y is H, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of the compound (IX) is as follows:

In the formula:

L ₂ is halogen, hydroxy, carbonyloxy;

The general formula of the compound (X) is as follows: (X)

In the formula:

m is 1-4;

The general formula of the compound (XI) is as follows:

In the formula:

The general formula of the compound (XII) is as follows:

The following examples are provided to illustrate the invention and not to limit it.

Example 1 Preparation of Compound 0V)

(1) Synthesis of N-6-(7-fluoro-3-oxo-3,4-dihydro-2H-benzo[b][l,4]oxazinylcarbimide methyl ester

Add 3.6 g of 6-amino-7-fluoro-2H-1,4-benzoxazine-3(4H)-one, 0.2 g of p-toluenesulfonic acid and 15 ml of trimethyl orthoformate to a 100 ml three-necked flask. And distilling off the methanol formed by the reaction and the excess trimethyl orthoformate, and cooling to room temperature. It was washed with water and dried to give 3.6 g of a solid.

_3⁄4 NMR (δ, CDC1 ₃ ): 8.941 (br, IH), 7.824-7.823 (dd, IH), 6.781-6.759 (dd, IH), 6.498-6.480 (dd, IH), 4.600 (s, 2H), 3.898 (s, 3H). MS: [M+H] 225丄

(2) Synthesis of 7-fluoro-6-(2-methylpropyleneamine)-2H-benzo[b][l,4]oxazine-3(4H)one

Add 7.3 g of 6-amino-7-fluoro-2H-1,4-benzoxazine-3(4H)-one and 75 ml of N,N-dimethylformamide (DMF) to a 100 ml three-necked flask, stir and cool. To -30 ° C. 4 ml of thionyl chloride was added dropwise, and after the completion of the dropwise addition, the temperature was raised to 40 °C. After reacting for 1 hour, it was cooled to room temperature, most of the DMF was removed under reduced pressure, 50 ml of 4M potassium carbonate solution was added, filtered, and the filter cake was washed with water and dried to give a solid (yield: 91%).

_3⁄4 NMR (δ, CDC1 ₃ ): 9.185 (br, IH), 7.524 (s, IH), 6.723-6.701 (dd, IH), 6.453-6.437 (dd, 1H) _: 4.561 (s, 2H), 3.019 ( s, 6H). MS: [M+H] 238.1.

(3) Synthesis of 6-(4-chlorobenzylideneamine)-7-fluoro-2H-benzo[b][l,4]oxazine-3(4H)one

Add 11.6 g of 6-amino-7-fluoro-2H-1,4-benzoxazine-3(4H)-one, 10 g of p-chlorobenzaldehyde and 120 ml of toluene to a 250 ml three-necked flask, reflux and distill off toluene, and add 10 ml hydrazine, hydrazine-dimethylformamide, refluxing, refluxing for 2 hours, heating was stopped, and the mixture was naturally cooled to room temperature under stirring, filtered, washed once with ethanol, washed with water and dried to give a solid, 15.8 g, yield 77 %.

_3⁄4 NMR (δ, CDC1 ₃ ): 8.562 (br, IH), 8.494 (s, IH), 7.851 (s, IH), 7.835 (s, IH), 7.464 (s, IH), 7.448 (s, IH) , 6.848-6.826 (dd, IH), 6.694-6.679 (dd, IH), 4.645 (s, 2H). MS: [M+H] 305.0

(4) Synthesis of 6-(4-nitrobenzylideneamine)-7-fluoro-2H-benzo[b][l,4]oxazine-3(4H)one

21.5 g of 6-amino-7-fluoro-2H-1,4-benzoxazine-3(4H)-one, 17.8 g of p-nitrobenzaldehyde and 140 ml of toluene were added to a 250 ml three-necked flask, and the toluene was refluxed and distilled off. It was cooled, filtered, washed once with ethanol, washed with water and dried to give 35.3 g of solid.

_3⁄4 NMR (δ, CDC1 ₃ ): 8.664 (s, IH), 8.344 (s, IH), 8.327 (s, IH), 8.084 (s, IH), 8.068 (s, IH), 7.715 (br, IH) , 6.881-6.859 (dd, IH), 6.740-6.725 (dd, IH), 4.663 (s, 2H). MS: [M+H] 316.1 Example 2 Preparation of Compound (VI)

(1) 6-(4-Chlorobenzylideneamine)-7-fluoro-4-(2-propynyl)-2H-benzo[b][l,4]oxazin-3(4H)one Synthesis 12.2 g of 6-(4-chlorobenzylideneamine)-7-fluoro-2H-benzo[b][l,4]oxazin-3(4H)one was added in a 250 ml three-necked flask. g potassium carbonate, O. lg tetrabutylammonium bromide and 100 ml DMF, stirred at room temperature. After adding 4.8 g of bromopropyne, the reaction was carried out at 60 ° C for 7 hours, desolvation, watering, filtration, washing with water, and drying to give 10.7 g of a solid, yield 78%.

_3⁄4 NMR (δ, CDC1 ₃ ): 8.540 (s, IH), 7.878 (s, IH), 7.861 (s, IH), 7.473 (s, IH), 7.455 (s, IH), 7.060-7.045 (dd, IH), 6.868-6.847 (dd, IH), 4.715-4.710 (dd, 2H), 4.666 (s, IH), 2.313-2.303 (t, 1H). MS: [M+H] 343.1

(2) 6-(4-Nitrobenzylideneamine)-7-fluoro-4-(2-propynyl)-2H-benzo[b][l,4]oxazin-3(4H) Synthesis of Ketones In a 250 ml three-necked flask, 12.6 g of 6-(4-nitrobenzylideneamine)-7-fluoro-2H-benzo[b][l,4]oxazin-3(4H)one was sequentially added. 16.5 g of potassium carbonate, 0.6 g of tetrabutylammonium bromide and 100 ml of DMF were stirred at -30 °C. 14 g of bromopropyne was added, and the mixture was reacted at 50 ° C for 4 hours, desolvated, water-slurryed, filtered, washed with water, and dried to give 13 g of a solid.

_3⁄4 NMR (δ, CDC1 ₃ ): 8.710 (s, 1H), 8.351 (s, 1H), 8.333 (s, 1H), 8.118 (s, 1H), 8.101 (s, 1H), 7.139-7.125 (dd, 1H), 6.897-6.876 (dd, 1H), 4.735-4.731 (dd, 2H), 4.691 (s, 1H), 2.329-2.319 (t, 1H). MS: [M+H] 354.1

Example 3 Synthesis of Compound (VII)

(1) Synthesis of 6-amino-7-fluoro-4-(2-propenyl)-2H-benzo[b][l,4]oxazine-3(4H)one

Add 31.9g of 6-(4-nitrobenzylideneamine)-7-fluoro-4-(2-propynyl)-2H-benzo[b][l,4]oxazine to a 250ml three-necked vial -3 (4H) ketone, 89 g of hydrochloric acid and 60 ml of ethanol were heated to 45 ° C and allowed to react for 3 hours. The solution was desolvated, the pH was adjusted to basic with sodium carbonate solution, and a large amount of solid was precipitated, filtered, washed to neutral, and dried to give 18.8 g of solid, yield 91%.

_3⁄4 NMR (δ, CDC1 ₃ ): 6.742-6.715 (dd, 1H), 6.661-6.640 (dd, 1H), 4.626-4.620 (dd, 2H), 4.550 (s, 1H), 3.645 (br, 2H), 2.288-2.276 (t, 1H). MS: [M+H] 221.2

(2) Synthesis of 6-amino-7-fluoro-4-(2-propenyl)-2H-benzo[b][l,4]oxazine-3(4H)one

Add 12g of 6-(4-chlorobenzylideneamine)-7-fluoro-4-(2-propynyl)-2H-benzo[b][l,4]oxazine-3 to a 250ml three-necked vial (4H) ketone, 60ml water and 50ml toluene, after stirring evenly, add 9.8g concentrated sulfuric acid at 0 °C, then warm up to 80 ° C, stir the reaction for about 4 hours, separate the liquid, add sodium carbonate solution to adjust the pH to alkali Sex, a large amount of solid was precipitated, filtered, and washed with water to give 6.70 g of solid, yield 88.3%.

Example 4 Synthesis of Compound (VIII)

(1) 2-(7-Fluoro-3-oxo-4-(2-propynyl)-3,4-dihydro-2H-benzo[b][l,4]oxazin-6-yl) Synthesis of -4,5,6,7-tetrahydrophthalimide

6g of 6-amino-7-fluoro-4-(2-propynyl)-2H-benzo[b][l,4]oxazin-3(4H)one, 4.1g tetrahydrogen was added to a 100ml three-necked vial Phthalic anhydride and 35 ml of acetic acid were heated to reflux. After completion of the reaction, the solution was desolvated, methanol-slurried, filtered, and dried to give 7 g of solid, yield 72%.

_3⁄4 NMR (δ, CDC1 ₃ ): 7.056-7.040 (dd, 1H), 6.912-6.888 (dd, 1H), 4.678 (s, 2H), 4.667-4.660 (dd, 2H), 2.540-2.435 (m, 4H ), 2.301-2.294 (dd, 1H), 1.845-1.839 (m, 4H). MS: [M+H] 355.1

(2) 2-(7-Fluoro-3-oxo-4-(2-propynyl)-3,4-dihydro-2H-benzo[b][l,4]oxazin-6-yl) Synthesis of -4,5,6,7-tetrahydrophthalimide Add 4.4 g of 6-amino-7-fluoro-4-(2-propynyl)-2H-benzo[b][l,4]oxazin-3(4H)one to a 100 ml three-necked flask and

35 ml of acetic acid, 12.2 g of tetrahydrophthalic anhydride was added at 0 ° C, and the reaction was refluxed under heating. After completion of the reaction, the solution was desolvated, methanol-boiled, filtered, and dried to give 5.7 g of a solid.

Claims

Claim

1. A benzolactam compound having the following formula:

In the formula:

X is 0, S;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1.

The benzolactam compound according to claim 1, wherein the compound is H or propynyl; is p-nitrophenyl or p-chlorophenyl; R ₃ is H or methyl ; X is 0; Y is H or F _; n is 0.

A process for producing a benzolactam compound (VI) according to claim 1, wherein the steps are as follows: Step (a): Compound (I) and compound (II) or compound (III) Compound (IV) is obtained by reacting with or without a catalyst in the presence or absence of a solvent,

In the formula:

Is 15, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

X is 0, S;

丫 is d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The formula of the compound (II) is: Ύ ( ⁿ ) where:

In the formula:

X is 0, S;

CM thiol, ( ₆ _ ₁₂ aryl;

The formula of the compound (IV) is:

In the formula:

X is 0, S;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of the compound (V) is:

(V) where:

It is a halogen, a sulfonate, a sulfate or a phosphate.

The method for producing a benzolactam compound (VI) according to claim 3, wherein the compound (II) in the step (a) is p-nitrobenzaldehyde, p-chlorobenzaldehyde or hydrazine. , Ν-dimethylformamide, the compound (III) is trimethyl orthoformate or triethyl orthoformate, the catalyst is a dehydrating agent or an acid, and the dehydrating agent is preferably a molecular sieve, anhydrous magnesium sulfate, Anhydrous sodium sulfate, anhydrous calcium chloride or thionyl chloride; the acid is preferably sulfuric acid, hydrochloric acid, acetic acid, phosphoric acid or p-toluenesulfonic acid; The solvent is an organic solvent, and the organic solvent is preferably toluene, xylene, methanol, ethanol, isopropanol or hydrazine, fluorenyl-dimercaptocarboxamide.

The method for producing a benzolactam compound (VI) according to claim 3, wherein the compound (V) in the step (b) is chloropropyne, bromopropyne or propyne methane. The acid ester, the acid binding agent is an inorganic base or an organic base; the inorganic base is preferably potassium carbonate, sodium carbonate, sodium hydrogencarbonate, sodium hydroxide or potassium hydroxide; the organic base is preferably piperidine, pyridine or triethylamine. The phase transfer catalyst is a quaternary ammonium salt, a quaternary phosphonium salt or a crown ether, and the quaternary ammonium salt is preferably tetrabutylammonium bromide, triethylphenylammonium chloride or tetrabutylammonium hydrogen sulfate. The quaternary phosphonium salt is preferably hexadecanyl tributylphosphonium bromide or n-butyl tri-n-octylphosphonium bromide, and the crown ether is preferably 18-crown ether-6.

6. Use of a benzolactam compound according to claim 1, characterized in that it is used for the preparation of compound (VIII), and the compound (VIII) has the following formula:

Where Q represents:

In the formula:

Is 15, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

X is 0, S;

丫 is 15, d 垸₅垸, halogen, CF ₃ , CN;

n is 0 or 1;

m is 1-4.

7. Use of a benzolactam compound according to claim 6, characterized by the step of the preparation method of the compound (VIII) Step (a) Compound (VI) gives compound (VII) under the action of a catalyst,

The general formula of the compound (VI) is as follows:

In the formula:

X is 0, S;

Y is H, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of the compound (VII) is as follows:

In the formula:

! ^为为. ^ Embankment group, C ₃ _ ₅ alkenyl, C ₃ _ ₅ alkynyl, C,

Is 15, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

X is 0, S;

Y is H, d_ ₅ fluorenyl, halogen, CF ₃ , CN;

n is 0 or 1;

The general formula of the compound (IX) is as follows:

In the formula:

L ₂ is halogen, hydroxy, carbonyloxy; The general formula of the compound (X) is as follows:

In the formula:

m is 1-4;

The general formula of the compound (XI) is as follows:

In the formula:

The general formula of the compound (XII) is as follows:

The use of the benzolactam compound according to claim 7, wherein the catalyst in the step (a) is an acid or a base, and the acid is preferably sulfuric acid, hydrochloric acid, acetic acid, phosphoric acid or p-toluene. One or more of an acid or zinc chloride; the base is preferably one or more of sodium hydroxide, potassium hydroxide, ethanolamine, hydrazine hydrate, piperidine, aqueous ammonia, ethylamine, n-propylamine or n-hexylamine. In the step (b), the organic solvent is preferably one or more of xylene, chlorobenzene, toluene, methylene chloride, trichloromethane or acetic acid.