Method for preparing 2-aryl malonamide and applications thereof

Abstract

Disclosed are a method for preparing 2-aryl malonamide and an application thereof. This method uses 2-(cyclohexenylidene) malononitrile as a raw material, which undergoes an aromatization-hydrolyzation reaction in the presence of an oxidant and water to produce 2-aryl malonamide by one step. Compared to the prior art, the method for preparing 2-aryl malonamide of this application has the following features and advantages: (1) this method employs a completely different synthetic strategy; (2) raw materials used in this method are easily obtained; (3) this method not only has high yield, but also does not require expensive metal catalysts. This method is lower-cost, suitable for the industrial production.

Claims

1. A method for preparing 2-aryl malonamide, comprising: subjecting compound 1 to an aromatization-hydrolyzation reaction in the presence of an oxidant and water to produce 2-aryl malonamide 2 by one step, as shown in the following reaction scheme: ##STR00002## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 each are independently hydrogen, a C.sub.1-C.sub.10 alkyl group, a C.sub.6-C.sub.12 aryl group or a heteroaryl group containing one or two atoms selected from nitrogen, oxygen and sulfur.

2. The method of claim 1, wherein R.sup.1 and R.sup.2 each are independently a C.sub.1-C.sub.3 alkyl group or a C.sub.6-C.sub.12 aryl group; R.sup.3 is a C.sub.1-C.sub.3 alkyl group; and R.sup.4 and R.sup.5 each are hydrogen.

3. The method of claim 2, wherein R.sup.1 and R.sup.2 each are ethyl, and R.sup.3 is methyl.

4. The method of claim 1, wherein the oxidant is peroxide, oxygen, air or an oxidizing acid; and a molar ratio of the oxidant to the compound 1 is 0.5-2.0:1.

5. The method of claim 4, wherein the oxidant is potassium persulfate or concentrated sulfuric acid; and the molar ratio of the oxidant to the compound 1 is 1.0-1.2:1.

6. The method of claim 1, wherein a temperature of the aromatization-hydrolyzation reaction 0-100 C.

7. The method of claim 6, wherein the temperature of the aromatization-hydrolyzation reaction is 60-80 C.

8. The method of claim 1, wherein the aromatization-hydrolyzation reaction is carried out in the presence of an acid.

9. The method of claim 8, wherein the acid is concentrated sulfuric acid.

10. A method for synthesizing Pinoxaden, comprising: 1) subjecting compound 1 to an aromatization-hydrolyzation reaction in the presence of an oxidant and water to produce 2-aryl malonamide 2 by one step, as shown in the following reaction scheme: ##STR00003## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 each are independently hydrogen, a C.sub.1-C.sub.10 alkyl group, a C.sub.6-C.sub.12 aryl group or a heteroaryl group containing one or two atoms selected from nitrogen, oxygen and sulfur; and 2) synthesizing Pinoxaden using the 2-aryl malonamide prepared in step 1).

Description

DETAILED DESCRIPTION OF EMBODIMENTS

(1) Some features of this application will be further illustrated below with reference to the embodiments, but these embodiments are not intended to limit this application.

(2) The raw materials used in the invention can be prepared by Knoevenagel condensation of cyclohexenone and malononitrile (J. Mol. Cata. A. Chem. 2003, 195 (1-2), 263).

Example 1 Preparation of 2-(2,6-diethyl-4-methylphenyl) malonamide

(3) 43.0 g of 2-(2,6-diethyl-4-methyl-2-ene-1-cyclohexylidene) malononitrile (0.20 mol), 54.1 g of potassium persulfate (0.2 mol) and 5.4 g of water (0.30 mol) were cooled to 0-5 C. Concentrated sulfuric acid was dropwise added to the reaction mixture which was then heated to 70 C. for reaction. After the reaction was completed, the reaction mixture was cooled, poured into ice water and extracted twice with ethyl acetate. The organic phases were combined, dried and crystallized by concentration to give 40.0 g of 2-(2,6-diethyl-4-methylphenyl) malonamide, and the yield was 80%.

(4) .sup.1H NMR (MeOD, 500 MHz): 6.99 (s, 2H), 4.81 (s, 1H), 2.60 (q, J=9.0 Hz, 4H), 2.32 (s, 3H), 1.22 (t, J=9.0 Hz, 6H).

(5) NMR (CDCl.sub.3, 125 MHz): 174.7, 145.0, 139.0, 130.2, 128.9, 48.9, 27.5, 21.2, 15.5.

Example 2 Preparation of 2-(2,6-diethyl-4-methylphenyl) malonamide

(6) 21.4 g of 2-(2,6-diethyl-4-methyl-2-ene-1-cyclohexylidene) malononitrile (0.10 mol) and 13.6 g of 30% hydrogen peroxide (0.12 mol) were cooled to 0-5 C. The reaction mixture was heated to 60 C. for reaction. After the reaction was completed, the reaction mixture was cooled, poured into ice water and extracted twice with ethyl acetate. The organic phases were combined, dried and crystallized by concentration to give 10.2 g of 2-(2,6-diethyl-4-methylphenyl) malonamide.

Example 3 Preparation of 2-(2,6-diethyl-4-methylphenyl) malonamide

(7) 32.1 g of 2-(2,6-diethyl-4-methyl-2-ene-1-cyclohexylidene) malononitrile (0.15 mol) and 6.7 g of water (0.30 mol) were cooled to 0-5 C. Concentrated sulfuric acid was dropwise added to the reaction mixture which was then heated to 80 C. for reaction. After the reaction was completed, the reaction mixture was cooled, poured into ice water and extracted twice with ethyl acetate. The organic phases were combined, dried and crystallized by concentration to give 32.7 g of 2-(2,6-diethyl-4-methylphenyl) malonamide, and the yield was 88%.

Example 4 Preparation of 2-(2,6-diethyl-4-methylphenyl) malonamide

(8) 214.3 g of 2-(2,6-diethyl-4-methyl-2-ene-1-cyclohexylidene) malononitrile (1.00 mol) and 27.0 g of water (1.50 mol) were cooled to 0-5 C. The reaction mixture was dropwise added with concentrated sulfuric acid and simultaneously introduced with oxygen. The reaction mixture was then heated to 80 C. for reaction. After the reaction was completed, the reaction mixture was cooled, poured into ice water and extracted twice with ethyl acetate. The organic phases were combined, dried and crystallized by concentration to give 136.6 g of 2-(2,6-diethyl-4-methylphenyl) malonamide.

Example 5 Preparation of 2-(3-methylphenyl) malonamide

(9) 15.0 g of 2-(3-methyl-2-ene-1-cyclohexylidene) malononitrile (0.09 mol), 25.7 g of potassium persulfate (0.09 mol) and 2.6 g of water (0.14 mol) were cooled to 0-5 C. Concentrated sulfuric acid was dropwise added to the reaction mixture which was then heated to 70 C. for reaction. After the reaction was completed, the reaction mixture was cooled, poured into ice water and extracted twice with ethyl acetate. The organic phases were combined, dried and crystallized by concentration to give 16.2 g of 2-(3-methylphenyl) malonamide, and the yield was 89%.

Example 6 Preparation of 2-(2,6-diphenyl-4-methylphenyl) malonamide

(10) 31.0 g of 2-(2,6-diphenyl-4-methyl-2-ene-1-cyclohexylidene) malononitrile (0.10 mol), 27.0 g of potassium persulfate (0.10 mol) and 2.7 g of water (0.15 mol) were cooled to 0-5 C. Concentrated sulfuric acid was dropwise added to the reaction mixture which was then heated to 70 C. for reaction. After the reaction was completed, the reaction mixture was cooled, poured into ice water and extracted twice with ethyl acetate. The organic phases were combined, dried and crystallized by concentration to give 19.6 g of 2-(2,6-diphenyl-4-methylphenyl) malonamide.

(11) .sup.1H NMR (MeOD, 500 MHz): 7.50-7.40 (m, 10H), 7.20 (s, 2H), 5.11 (s, 1H), 2.44 (s, 3H).

Example 7 Preparation of Pinoxaden

(12) 12.4 g of 2-(2,6-diethyl-4-methylphenyl) malonamide (0.05 mol), 10.5 g of hexahydro-1,4,5-oxadiazepine dihydrochloride (0.06 mol) and 20.2 g of triethylamine (0.20 mol) were stirred and refluxed in xylene for reaction. After the reaction was completed, the reaction mixture was cooled, added with 10.8 g of pivaloyl chloride (0.09 mol) and reacted at room temperature. After the reaction was completed, the reaction mixture was adjusted with dilute hydrochloric acid until pH was acidic and extracted with ethyl acetate. The organic phases were dried and crystallized by concentration to give 14.4 g of Pinoxaden, and the yield was 72%.

(13) .sup.1H NMR (CDCl.sub.3, 500 MHz, TMS): 8.88 (s, 2H), 4.28-4.26 (m, 2H), 3.94-3.93 (m, 2H), 3.89-3.83 (m, 4H), 2.56-2.47 (m, 2H), 2.45-2.40 (m, 2H), 2.39 (s, 3H), 1.12 (t, J=9.0 Hz, 3H), 1.23 (s, 9H).