CN1623991A - Substituted aza five-membered/six-membered ring-2,4-diketone compound and its synthesis method - Google Patents

Abstract

A process for one-step synthesizing 3-dialkylthiomethylene azapentacycle/hexacycle-2,4-dione from alpha-acyl-alpha-amine/ammonia formacyl dithioketene, and the compound (polysubstitutent pyrrolidone or polysubstitutent hydropyridone) prepared by said process are disclosed.

Description

Substituted aza five-membered/six-membered ring-2,4-diketone compound and its synthesis method

Technical field:

The invention discloses a method for one-step synthesis of 3-dialkylthiomethylene aza five-membered/six-membered ring-2,4-dione starting from α-acyl-α-amine/carbamoyl dithioketene The synthesis method and the compound synthesized by the method belong to the technical field of organic synthesis.

Background technique:

Azacyclic ketones are attracting people's attention (Lockhart I.M., Webb N.E., Wright M., Winder C.V., Vamer P..J.Med.Chem., 1972, 15, 935 and references cited therein.Martinelli M., Peterson B..Tetrahedron Lett.1990, 31, 5401.Philip M., Sabol, etc.Tetrahedron, 2003, 59, 2953 and references cited therein). Such as MG-1 and pyrrolidone drugs that have a certain effect on cardiovascular diseases (For a review, see: Palfreyman, M..N.Souness, J.E.Progress in Medicinal Chemistry, 1996, 33, 1) and drugs that have been used in clinical research Piperidone compounds (Shorvonm, Simon.TeLancet, 2001, 358, 9296, 1885 and references cited therein), etc. In synthesis, pyrrolidin-2-ones and piperidin-2-ones can be synthesized by intramolecular dehydration of ω-amino acids (Collum D.B., Ganem B..J.Org.Chem., 1978, 43, 4393.Bartra-Font A..Tetahedron Lett, 1980, 21, 2443), can also start from the ring system containing oxygen atom or sulfur atom, and use the nucleophilicity of nitrogen atom to replace heteroatom to construct nitrogen heterocyclic ring system (Baussanne I., Chiaroni A., Husson H.P., Riche C., Royer J.. Tetrahedron Lett., 1994, 35, 3931. Isabelle Baussanne, Catherine Travers, Jacques Royer. Tetrahedron: Asymmetry, 1998, 9, 797.), or Starting from the product obtained by the reaction of β-amino acid ester and halogenated acetate, an intramolecular nucleophilic addition and elimination reaction occurs in an alkaline medium to generate azacyclic ketones (Wanga Dawei Mab. Tetrahedron: Asymmetry, 2001 , 12, 725.). Although the first method is easy to operate, it lacks the diversity of products due to the limitation of raw materials. The second and third methods have problems such as many steps and cumbersome operation.

Invention content:

The present invention provides a method for one-step synthesis of 3-dialkylthiomethylene aza five-membered/six-membered ring-2,4-diketone starting from α-acyl-α-amine/carbamoyl dithioketene The synthesis method, the reaction is atom-economical, and the product becomes an important organic synthesis intermediate with aza five-membered/six-membered ring system structural units because it contains an active carbonyl group on the heterocycle and retains a dithioketal group. A general method for the preparation of its synthons α-acyl-α-amine/carbamoyl dithioketene starting from readily available ethyl acetoacetate is provided.

Substituted 3-dialkylthiomethylene aza five-membered/six-membered ring-2,4-diketone 1, α-acyl-α-amine/carbamoyl dithioketene 2 and aldehyde involved in the present invention 3 and Compound 2 and Compound 3 are reacted in one step to obtain the synthetic strategy of Compound 1 with the following Scheme 1:

Scheme 1

When n=1; m=1:

R ¹ is a hydrogen atom; each carbon atom of the alkyl group is connected with nitro, cyano, amino, imino, mercapto, phenyl C ₁ -C ₄ alkyl; amino; the nitrogen atom of the amine group is connected with C ₁ -C ₄ alkyl amino group; aryl amino group has chlorine, bromine, iodine, amino, C ₁ -C ₄ hydrocarbon amino group, nitro group, cyano group, acyl group, carboxyl group, sulfonic acid group, C ₁ -C ₄ hydrocarbon group, arylamino group of C ₁ -C ₄ hydrocarbon oxygen group; formyl group; carbamoyl group; C ₁ -C ₄ alkyl group connected to the carbonyl of the acyl group, chlorine, bromine, Acyl of iodine, amino, C ₁ -C ₄ hydrocarbon amino, nitro, cyano, acyl, carboxyl, sulfonic acid, C ₁ -C ₄ hydrocarbon, aryl of C ₁ -C ₄ hydrocarbon oxy; sulfonyl ; The aryl group in the arylsulfonyl group is phenyl and there are chlorine, bromine, iodine, nitro, cyano, sulfonic acid groups, various C ₁ -C ₄ hydrocarbon groups and various C ₁ -C ₄ on the benzene ring Hydrocarbyl alkoxy benzenesulfonyl; pyrrolyl; imidazolyl; furyl; thienyl; pyridyl; benzopyrrolyl; quinolinyl; indolyl; benzimidazolyl; benzofuryl; benzo Thienyl; pyrimidinyl; pyrazinyl; triazinyl; purinyl; naphthyl; anthracenyl; phenanthrenyl; fluorenyl; carbazolyl; furfuryl; vinyl; , cyano group, sulfonic acid group, various C ₁ -C ₄ hydrocarbon groups and various C ₁ -C ₄ hydrocarbon groups alkoxy and alkoxycarbonyl, aryl in aryloxycarbonyl is phenyl and various C ₁ - C ₄ hydrocarbon group and various C ₁ -C ₄ alkoxy substituted phenyl vinyl groups; ethynyl.

^R is furyl; thienyl; pyridyl; benzofuryl; benzothienyl; quinolinyl; benzoquinolyl; pyrimidinyl; pyrazinyl; triazinyl; purinyl; indolyl; The aryl group of the aryl group is a phenyl group with an electron-withdrawing group attached to the benzene ring.

Z is nitrogen, oxygen, sulfur atom, sulfoxide group (-SO), sulfone group (-SO ₂ ), imino group (-NH).

R ³ is various C ₁ -C ₆ hydrocarbon groups; the aryl of benzyl is phenyl and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid, various C ₁ - C ₆ hydrocarbon groups and aryl groups of alkoxy groups of various C ₁ -C ₆ hydrocarbon groups; aryl groups are phenyl groups and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid groups, Various C ₁ -C ₆ hydrocarbon groups and various C ₁ -C ₆ hydrocarbon groups alkoxy-substituted phenyl groups.

R ⁴ is various C ₁ -C ₆ hydrocarbon groups; the aryl of benzyl is phenyl and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid, various C ₁ - C ₆ hydrocarbon group and alkoxy-substituted phenyl of various C ₁ -C ₆ hydrocarbon groups; aryl is phenyl and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid groups are attached to the benzene ring , various C ₁ -C ₆ hydrocarbon groups and alkoxy-substituted phenyl groups of various C ₁ -C ₆ hydrocarbon groups.

The dotted lines between R ³ and R ⁴ represent various bonding relationships, such as: R ³ and R ⁴ are (CH ₂ ) _x , where x=1, 2, 3, 4. When x=1, 2, 3, 4, the hydrogen atoms on each methylene group of the chain segment can be respectively replaced by halogen atoms such as chlorine, bromine, iodine; nitro; cyano; sulfonic acid group; hydroxyl; amino; mercapto; Carboxyl; Alkoxycarbonyl of various C ₁ -C ₆ hydrocarbyls; Various C ₁ -C ₆ hydrocarbyls; Alkoxy of various C ₁ -C ₆ hydrocarbyls; Alkylthio of various C ₁ -C ₆ hydrocarbyls; The aryl of benzyl is phenyl and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid, various C ₁ -C ₆ hydrocarbon groups and various C ₁ -C ₆ hydrocarbon groups are connected to the benzene ring Alkoxy-substituted phenyl; aryl is phenyl and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid, various C ₁ -C ₆ hydrocarbon groups and various Alkoxy-substituted phenyl of C ₁ -C ₆ hydrocarbyl.

When Z is a nitrogen atom, R ⁴ is various C ₁ -C ₆ hydrocarbon groups.

When n=2; m=0, R ¹ , R ³ , R ⁴ , Z and the various bonding relationships represented by the dotted lines between R ³ and R ⁴ are the same as n=1; m=1 when R ¹ , R ³ , R ⁴ , Z and the dotted lines between R ³ and R ⁴ represent the same linkages. ^R2 is pyrrolyl; imidazolyl; benzopyrrolyl; benzimidazolyl; quinolinyl; benzoquinolyl; pyrimidinyl; ; The aryl group is a phenyl group and a phenyl group with an electron-donating group attached to the benzene ring.

The technical solution of the present invention is: starting from ethyl acetoacetate, first synthesize ethyl 2-dialkylthiomethylene-3-carbonyl butyrate, then hydrolyze 2-dialkylthiomethylene-3-carbonyl Ethyl butyrate gives 2-dialkylthiomethylene-3-oxobutanoic acid. Starting from 2-dialkylthiomethylene-3-carbonylbutyric acid, via 2-dialkylthiomethylene-3-carbonylbutyryl chloride and 2-dialkylthiomethylene-3-carbonylbutyryl chloride The compound represented by general formula 2 is synthesized by one-pot reaction with amine (R ¹ NH ₂ ) at normal temperature, and the compound represented by general formula 1 is synthesized by reacting compound 2 with aldehyde 3 under basic conditions.

The positive effect of the present invention is: starting from readily available raw materials (ethyl acetoacetate or acetoacetamide/amine), via α-acyl-α-ammonia/carbamoyl dithioketene intermediate 2, under mild conditions Synthesize compounds (polysubstituted pyrrolidones and polysubstituted hydropyridones) that have potential pharmacological activity and can be used as important intermediates in organic synthesis. The reaction is atom-economical. The structural characteristics of the reaction products (multi-substituted pyrrolidones and multi-substituted hydropyridones) are as follows: the nitrogen heterocycle contains active carbonyl groups and α-carbonyl dithioketal groups with Push-Pull electron interaction, and is expected to become a complex structural heterocyclic group. It is an important synthetic intermediate of cyclic compounds and even pyrrole ring system and piperidine ring system natural products.

Detailed ways:

The solvent used for the reaction is: halogenated hydrocarbons, such as chloroform, methylene chloride, ethylene dichloride, and carbon tetrachloride. C ₁ -C ₆ hydrocarbon-based ethers, such as methyl ethyl ether, diethyl ether, n-butyl ether. Esters of C ₁ -C ₆ hydrocarbon groups, such as ethyl acetate and n-butyl acetate. C ₁ -C ₆ hydrocarbon-based alcohols, such as methanol, ethanol, n-butanol. Amides, such as dimethylformamide, dimethylacetamide, dimethyl sulfoxide. Liquid hydrocarbons, such as petroleum ether, cyclohexane, benzene, nitrobenzene and some other commonly used organic solvents.

Example 1

In a 100ml Erlenmeyer flask, add 50ml of DMF, 15.2g (110mmol) of anhydrous K ₂ CO ₃ , stir for 10 minutes, then add amine/carbamoyl acetone (500mmol), stir for 0.5 hours, under ice-cooling Add 4 ml (55 mmol) of carbon disulfide and continue to stir for 1 hour, add dihalogenated hydrocarbon (55 mmol), stir for 10 hours, pour into 150 ml of water, a large amount of white solid precipitates, filter with suction, and dry to obtain a light yellow solid product α-ammonia / carbamoyl dithioketene 2. The reaction is shown in the following formula, and the data is shown in the table below:

R ¹ =H; R, R = (CH ₂ ) ₂ 77.2%

R ¹ =H; R, R = (CH ₂ ) ₃ 78.5%

R ¹ =H; R, R = (CH ₂ ) ₄ 76.0%

R ¹ =H; R = CH ₃ 73.2%

^R1 = H; R = Bn 72.0%

R ¹ =ClC ₆ H ₄ ; R, R = (CH ₂ ) ₂ 93.0%

R ¹ =ClC ₆ H ₄ ; R, R = (CH ₂ ) ₃ 94.2%

R ¹ =ClC ₆ H ₄ ; R, R = (CH ₂ ) ₄ 89.5%

R ¹ =ClC ₆ H ₄ ; R=CH ₃ 85.0%

R ¹ = ClC ₆ H ₄ ; R = Bn 88.3%

R ¹ =2,4-Me ₂ C ₆ H ₃ ; R,R = (CH ₂ ) ₂ 93.2%

R ¹ =2,4-Me ₂ C ₆ H ₃ ; R,R=(CH ₂ ) ₃ 94.0%

R ¹ =2,4-Me ₂ C ₆ H ₃ ; R,R=(CH ₂ ) ₄ 91.3%

R ¹ = 2,4-Me ₂ C ⁶ H ₃ ; R = CH ₃ 87.6%

R ¹ = 2,4-Me ₂ C ₆ H ₃ ; R = Bn 86.0%

Example 2

In a 100ml Erlenmeyer flask, add 50ml of DMF, 15.2g (110mmol) of anhydrous K ₂ CO ₃ , stir for 10 minutes, then add 6.4ml (500mmol) of ethyl acetoacetate, stir for 0.5 hour, under ice-cooling Add 4 ml (55 mmol) of carbon disulfide and continue stirring for 1 hour, add 1,3-dibromopropane (or 1,2-dibromoethane and 1,4-dibromobutane) (55 mmol), stir for 10 hours, pour into A large amount of white solid was precipitated in 150 ml of water, which was filtered by suction and dried to obtain ethyl 2-[1,3]dithia-2-methylene-3-oxobutanoate as a white solid product with a yield of 85.0%. The reaction is shown in the following formula, and the data are shown in the table below.

R, R=(CH ₂ ) ₂ 93.8%

R, R=(CH ₂ ) ₃ 95.0%

R, R=(CH ₂ ) ₄ 91.3%

R= _CH3 87.5%

R＝Bn 86.2%

According to the hydrolysis method of ester (edited by Fan Nengting, Organic Synthesis Book, Beijing Science Press. 1981, 28), the product obtained above was hydrolyzed to synthesize 2-dialkylthiomethylene-3-carbonylbutanoic acid. Yield >85%.

Put dry CH ₂ Cl ₂ (or THF, 10 mL) and compound 2-(2,5-dithiocyclopentyl) methylene-3-oxobutanoic acid (408.5 mg , 2.0mmol), after stirring for 15min, SOCl ₂ (285.6mg, 2.4mmol) was added, heated to reflux in a hot water bath for 3min under electromagnetic stirring, and the heating was stopped. After the reaction system was cooled to room temperature, Et ₃ N (1010.0 mg, 10.0 mmol) was added dropwise. Stir at room temperature (about 0.5 h), and add R ¹ NH ₂ (2.0 mmol) to the system after TLC detects that the substrate disappears. Stirring was continued at room temperature, and TLC was detected until the nascent acid chloride disappeared. The solvent in the reaction system was discarded by rotary evaporation under reduced pressure, the solid was washed with water, dissolved in chloroform (70 mL), and filtered with suction. The filtrate was washed with water (40mL×2), the chloroform layer was dried over anhydrous magnesium sulfate, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 3:2) to obtain a light yellow solid product α-acyl-α-ammonia/ Carbamoyl dithioketene 2. The reaction is shown in the following formula, and the data is shown in the table below:

R ¹ =OH 79.3%

R ¹ =nC ₄ H ₉ 70.5%

R ¹ = o-BrC ₆ H ₄ 83.6%

R ¹ =α-naphithyl 75.3%

R ¹ =β-naphithyl 75.0%

R ¹ =p-CH ₃ C ₆ H ₄ 70.3%

R ¹ =p-NO ₂ C ₆ H ₄ 70.2%

Example 3

Ethyl 2-dialkylthiomethylene-3-carbonylbutanoate (5 mmol) synthesized in Example 2 and aromatic aldehyde ArCHO (6 mmol) were added to ethanol (15 mL) and stirred in an ice-water bath for 5 min. Add 1N NaOEt/EtOH solution (6mL, equivalent to 6mmol EtONa, prepared now) dropwise, and stir at room temperature. TLC detects that the reaction causes the disappearance of the substrate (it takes about 4 h). The solvent ethanol was evaporated under reduced pressure, and the residual solid after evaporation of ethanol was quickly washed with hydrochloric acid (10 mL, 1N), filtered with suction, washed with water, and dried to obtain a yellow solid -α-cinnamoyl-α-carboxy dithioketene.

Put dry CH ₂ Cl ₂ (or THF, 10 mL) and compound α-cinnamoyl-α-carboxydithioketene (2.0 mmol) into a 50-ML dry three-necked bottle, stir for 15 min, then add SOCl ₂ ( 285.6mg, 2.4mmol), heated to reflux in a hot water bath for 3min under electromagnetic stirring, and stopped heating. After the reaction system was cooled to room temperature, Et ₃ N (1010.0 mg, 10.0 mmol) was added dropwise. Stir at room temperature (about 1 h), and add R ¹ NH ₂ (2.0 mmol) to the system after TLC detects that the substrate disappears. Stirring was continued at room temperature, and TLC was detected until the nascent acid chloride disappeared. The solvent in the reaction system was discarded by rotary evaporation under reduced pressure to obtain a crude product, which was refined according to the refining method in Example 2 to obtain α-cinnamoyl-α-ammonia/carbamoyl dithioketene 2. The reaction is shown in the following formula, and the data is shown in the table below (yield is the total yield of two-step reaction):

R ¹ =H; R ² =2-pyridiuyl; R ³ , R ⁴ =(CH) ₂ 76.6%

R ¹ =H; R ² =4-MeC ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 86.2%

R ¹ =H; R ² =4-UO ₂ C ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 73.2%

R ¹ =H; R ² =4-MeOC ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 87.0%

R ¹ =H; R ² =4-MeOC ₆ H ₄ ; R ³ , R ⁴ =(CH) ₃ 85.6%

R ¹ =ph; R ² =2-pyridiuyl; R ³ , R ⁴ =(CH) ₂ 78.5%

R ¹ =4-MeC ₆ H ₄ ; R ² =2-pyridiuyl; R ³ , R ⁴ =(CH) ₂ 79.3%

R ¹ =4-UO ₂ C ₆ H ₄ ; R ² =2-pyridiuyl; R ³ , R ⁴ =(CH) ₂ 70.2%

R ¹ =4-MeC ₆ H ₄ ; R ² =p-UO ₂ C ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 78.5%

R ¹ =4-UO ₂ C ₆ H ₄ ; R ² =p-MeC ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 77.2%

R ¹ =4-ClC ₆ H ₄ ; R ² =p-UO ₂ C ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 75.6%

Example 4

Add α-acyl-α-ammonia/carbamoyl dithioketene 2 (2.0 mmol) and aromatic aldehyde 3 (2.2 mmol) into ethanol (10.0 mL), and stir for 5 min. Add the EtONa/ethanol solution (2.4 mL, 1N) prepared now dropwise under electromagnetic stirring in an ice-water bath and stir at room temperature for about 1 h. TLC detected that the reaction substrate 2 disappeared. Adjust the pH value to about 7, filter with suction, and wash the solid with water (10mL×2). The ethanol in the filtrate was distilled off under reduced pressure, the residue was washed with water (10 mL×2), and the obtained solids were combined twice. The solid was dried to give crude product. Separation by silica gel G column chromatography, eluting with petroleum ether-ethyl acetate (6:1, v/v) gave the slightly yellow product 1. The reaction is shown in the following formula, and the data is shown in the table below:

n=1 m=1 R ¹ =2,4-Me ₂ C ₆ H ₃ ; R ² =2-pyridyl; R ³ , R ⁴ =(CH) ₂ 83.0%

n=1 m=1 R ¹ =2,4-Me ₂ C ₆ H ₃ ; R ² =4-pyridyl; R ³ , R ⁴ =(CH) ₂ 85.0%

n=1 m=1 R ¹ =2,4-Me ₂ C ₆ H ₃ ; R ² =3-O ₂ UC ₆ H ₄ l; R ³ , R ⁴ =(CH) ₂ 81.2%

n=1 m=1 R ¹ =2-MeC ₆ H ₄ ; R ² =2-pyridyl; R ³ , R ⁴ =(CH) ₂ 86.3%

n=1 m=1 R ¹ =2-MeC ₆ H ₄ ; R ² =2-pyridyl; R ³ , R ⁴ =(CH) ₂ 85.2%

n=1 m=1 R ¹ =2-MeC ₆ H ₄ ; R ² =4-O ₂ UC ₆ H ₄ ; R ³ , R ⁴ =(CH) ₃ 80.6%

n=1 m=1 R ¹ =4-MeC ₆ H ₄ ; R ² =2-pyridyl; R ³ , R ⁴ =(CH) ₂ 87.3%

n=1 m=1 R ¹ =4-O ₂ UC ₆ H ₄ ; R ² =2-pyridyl; R ³ , R ⁴ =(CH) ₂ 78.2%

n=1 m=1 R ¹ =H; R ² =2-pyridyl; R ³ , R ⁴ =(CH) ₂ 68.5%

n=1 m=1 R ¹ =4-ClC ₆ H ₄ ; R ² 0=4-pyridyl; R ³ , R ⁴ =(CH) ₂ 88.6%

n=1 m=1 R ¹ =4-ClC ₆ H ₄ ; R ² =2-pyridyl; R ³ , R ⁴ =(CH) ₂ 86.2%

n=1 m=1 R ¹ =4-ClC ₆ H ₄ ; R ² =3-pyridyl; R ³ , R ⁴ =(CH) ₂ 83.2%

n=2 m=0 R ¹ =ph ₄ ; R ² =ph; R ³ , R ⁴ =(CH) ₂ 78.8%

n=2 m=0 R ¹ =4-MeC ₆ H ₄ ; R ² =4-MeC ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 72.9%

n=2 m=0 R ¹ =4-MeC ₆ H ₄ ; R ² =ph; R ³ , R ⁴ =(CH) ₂ 75.3%

Example 5

Add α-cinnamoyl-α-ammonia/carbamoyl dithioketene 2 (2.0 mmol) into ethanol (10.0 mL), and stir for 5 min. Add the EtONa/ethanol solution (2.4 mL, 1N) prepared now dropwise under electromagnetic stirring in an ice-water bath and stir at room temperature for about 1 h. TLC detected that the reaction substrate 2 disappeared. Adjust the pH value to about 7, filter with suction, and wash the solid with water (10mL×2). The ethanol in the filtrate was distilled off under reduced pressure, the residue was washed with water (10 mL×2), and the obtained solids were combined twice. The solid was dried to give crude product. Separation by silica gel G column chromatography and eluting with petroleum ether-ethyl acetate (6:1, v/v) gave the slightly yellow product 3-dialkylthiomethylenepyrrolidine-2,4-dione derivative 1. The reaction is shown in the following formula, and the data is shown in the table below:

n=1 m=1 R ¹ =2-MeC ₆ H ₄ ; R ² =4-pyridyl; R ³ , R ⁴ =(CH) ₂ 76.3%

n=1 m=1 R ¹ =Ph; R ² =2-pyridyl; R ³ , R ⁴ =(CH) ₂ 78.5%

n=1 m=1 R ¹ =4-ClC ₆ H ₄ ; R ² =4-0 ₂ NC ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 77.6%

n=2 m=0 R ¹ =4-MeC ₆ H ₄ ; R ² =4-MeC ₆ H ₄ ; R ³ , R ⁴ =(CH) ₂ 66.3%

n=2 m=0 R ¹ =4-MeC ₆ H ₄ ; R ² =ph; R ³ , R ⁴ =(CH) ₂ 65.2%

n=2 m=0 R ¹ =ph; R ² =ph; R ³ , R ⁴ =(CH) ₂ 70.6%

Claims (3)

1. The following general formula 1 compound has the following structure:

Among them, when n=1; m=1: R ¹ is a hydrogen atom; each carbon atom of the alkyl group is connected with nitro, cyano, amino, imino, mercapto, phenyl C ₁ -C ₄ alkyl; amino; the nitrogen atom of the amine group is connected with C ₁ -C ₄ alkyl amino group; aryl amino group has chlorine, bromine, iodine, amino, C ₁ -C ₄ hydrocarbon amino group, nitro group, cyano group, acyl group, carboxyl group, sulfonic acid group, C ₁ -C ₄ hydrocarbon group, arylamino group of C ₁ -C ₄ hydrocarbon oxygen group; formyl group; carbamoyl group; C ₁ -C ₄ alkyl group connected to the carbonyl of the acyl group, chlorine, bromine, Acyl of iodine, amino, C ₁ -C ₄ hydrocarbon amino, nitro, cyano, acyl, carboxyl, sulfonic acid, C ₁ -C ₄ hydrocarbon, aryl of C ₁ -C ₄ hydrocarbon oxy; sulfonyl ; The aryl group in the arylsulfonyl group is phenyl and there are chlorine, bromine, iodine, nitro, cyano, sulfonic acid groups, various C ₁ -C ₄ hydrocarbon groups and various C ₁ -C ₄ on the benzene ring Hydrocarbyl alkoxy benzenesulfonyl; pyrrolyl; imidazolyl; furyl; thienyl; pyridyl; benzopyrrolyl; quinolinyl; indolyl; benzimidazolyl; benzofuryl; benzo Thienyl; pyrimidinyl; pyrazinyl; triazinyl; purinyl; naphthyl; anthracenyl; phenanthrenyl; fluorenyl; carbazolyl; furfuryl; vinyl; , cyano group, sulfonic acid group, various C ₁ -C ₄ hydrocarbon groups and various C ₁ -C ₄ hydrocarbon groups alkoxy and alkoxycarbonyl, aryl in aryloxycarbonyl is phenyl and various C ₁ - C ₄ hydrocarbon group and various C ₁ -C ₄ alkoxy substituted phenyl vinyl groups; ethynyl. ^R is furyl; thienyl; pyridyl; benzofuryl; benzothienyl; quinolinyl; benzoquinolyl; pyrimidinyl; pyrazinyl; triazinyl; purinyl; indolyl; The aryl group of the aryl group is a phenyl group with an electron-withdrawing group attached to the benzene ring. Z is nitrogen, oxygen, sulfur atom, sulfoxide group (-SO), sulfone group (-SO ₂ ), imino group (-NH). R ³ is various C ₁ -C ₆ hydrocarbon groups; the aryl of benzyl is phenyl and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid, various C ₁ - C ₆ hydrocarbon groups and aryl groups of alkoxy groups of various C ₁ -C ₆ hydrocarbon groups; aryl groups are phenyl groups and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid groups, Various C ₁ -C ₆ hydrocarbon groups and various C ₁ -C ₆ hydrocarbon groups alkoxy-substituted phenyl groups. R ⁴ is various C ₁ -C ₆ hydrocarbon groups; the aryl of benzyl is phenyl and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid, various C ₁ - C ₆ hydrocarbon group and alkoxy-substituted phenyl of various C ₁ -C ₆ hydrocarbon groups; aryl is phenyl and fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid groups are attached to the benzene ring , various C ₁ -C ₆ hydrocarbon groups and alkoxy-substituted phenyl groups of various C ₁ -C ₆ hydrocarbon groups. The dotted line between R ³ and R ⁴ represents various bonding relationships, such as: R ³ and R ⁴ are (CH ₂ ) _x , (x=1,2,3,4); x=1,2,3,4 , the hydrogen atoms on each methylene group of the chain segment can be replaced by halogen atoms such as chlorine, bromine, iodine; nitro; cyano; sulfonic acid; hydroxyl; amino; mercapto; _{carboxyl ;} Alkoxycarbonyl of hydrocarbyl; various C ₁ -C ₆ hydrocarbyl; alkoxy of various C ₁ -C ₆ hydrocarbyl; alkylthio of various C ₁ -C ₆ hydrocarbyl; aryl of benzyl is phenyl and Phenyl substituted by fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid, various C ₁ -C ₆ hydrocarbon groups and various C ₁ -C ₆ hydrocarbon groups on the benzene ring; Aryl is phenyl and alkoxy with fluorine, chlorine, bromine, iodine, nitro, cyano, sulfonic acid, various C ₁ -C ₆ hydrocarbon groups and various C ₁ -C ₆ hydrocarbon groups attached to the benzene ring Substituted phenyl groups. When Z is a nitrogen atom, R ⁴ is various C ₁ -C ₆ hydrocarbon groups. When n=2; m=0, R ¹ , R ³ , R ⁴ , Z and the various bonding relationships represented by the dotted lines between R ³ and R ⁴ are the same as n=1; m=1 when R ¹ , R ³ , R ⁴ , Z and the dotted lines between R ³ and R ⁴ represent the same linkages. ^R2 is pyrrolyl; imidazolyl; benzopyrrolyl; benzimidazolyl; quinolinyl; benzoquinolyl; pyrimidinyl; ; The aryl group is a phenyl group and a phenyl group with an electron-donating group attached to the benzene ring. 2. Starting from ethyl acetoacetate, first synthesize ethyl 2-dialkylthiomethylene-3-carbonyl butyrate, and then hydrolyze ethyl 2-dialkylthiomethylene-3-carbonylbutyrate to obtain 2 - Dialkylthiomethylene-3-oxobutanoic acid. Starting from 2-dialkylthiomethylene-3-carbonylbutyric acid, via 2-dialkylthiomethylene-3-carbonylbutyryl chloride and 2-dialkylthiomethylene-3-carbonylbutyryl chloride The compound represented by general formula 2 is synthesized by one-pot reaction with amine (R ¹ NH ₂ ) at room temperature. 3. Starting from α-acyl-α-amine/carbamoyl dithioketene 2, react with aldehyde 3 under basic conditions to synthesize substituted aza five-membered/six-membered ring-2,4 represented by general formula 1 - A method for the synthesis of diketone compounds. Include the following steps: The solvent used for the reaction is: halogenated hydrocarbons, such as chloroform, dichloromethane, dichloroethane, carbon tetrachloride; C ₁ -C ₆ hydrocarbon-based ethers: such as methyl ethyl ether, diethyl ether, n-butyl ether; C ₁ -C ₆ hydrocarbon-based esters: such as ethyl acetate, n-butyl acetate; C ₁ -C ₆ hydrocarbon-based alcohols: such as methanol, ethanol, n-butanol; amides: such as dimethylformamide, di Methyl acetamide; dimethyl sulfoxide; liquid hydrocarbons: such as petroleum ether, cyclohexane, benzene, nitrobenzene and some other commonly used organic solvents. Starting from α-acyl-α-amine/carbamoyl dithioketene, react in the presence of a base at 0 to 200°C for 10 minutes to one week to synthesize 3-dialkylthiomethylene azapenta in one step Member/six-membered ring-2,4-dione derivatives.