RU2333908C1 - Method for obtaining 2-ethyl-3,5-dimethylpiridin - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to methods for obtaining heterocyclic compounds, namely, to method for obtaining 2-ethyl-3,5-dimethylpiridin. The method consists in interaction of ammonia with propionic aldehide in presence of catalyst crystalhydrate of lanthanide nitrate Ln(NO₃)₃·6H₂O, where Ln=Pr, Nd and Tb, molar ratio ammonia: aldehide: catalyst being 50:150:1, at room temperature in DMF during 24 hours. The said compounds are widely used for synthesis of medications, as well as in production of dyes, means of chemical protection of plants, as extragents, sorbents and inhibitors of corrosion.

EFFECT: obtaining 2-ethyl-3,5-dimethylpiridin with reduction of content of by-products, increase in target product output to 67%, reduction of output production price.

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Description

The present invention relates to methods for producing heterocyclic compounds, specifically to a method for producing 2-ethyl-3,5-dimethylpyridine

Pyridine and its derivatives are structural fragments of many biologically active compounds and are widely used in the synthesis of drugs, including anti-HIV drugs, as well as in the manufacture of dyes, chemical plant protection products, as extractants, sorbents and corrosion inhibitors.

The known method (Yu.D.Dolskaya, G.Ya. Kondratyev. Catalytic synthesis of alkylpyridines from 2-azarlene-1,3 and olefins. Izv. AN SSSR. Ser. Chem. 1970. No. 9. P.2123-2124) obtaining 2-ethyl-3,5-dimethylpyridine with a yield of 17% in the reaction of N-propyleneidepenylamine with propylene under the action of a catalyst K ₂ O / Al ₂ O ₃ at 410-450 ° C.

The disadvantages of this method include the low yield of the target product, high temperature (high energy consumption), and the inaccessibility of N-propylidenepropenylamine (synthesis is carried out by the reaction of propionic aldehyde with allyl (or propenyl) amine at 410-450 ° C).

Closest to the invention is a method (Pat. Germany No. 1276644. Application. 10/06/1964, publ. 04/30/1969) to obtain 2-ethyl-3,5-dimethylpyridine by the reaction of condensation of ammonia with propionic aldehyde under the influence of a catalyst Co ₃ (PO ₄ ) ₂ at 350-420 ° С. In the reaction, a mixture of three pyridine bases is formed: 2-ethyl-3,5-dimethyl, 4-ethyl-3,5-dimethyl and 3,4-dimethylpyridines. The yield of the target product does not exceed 30%.

The disadvantages of this method include: low selectivity and yield of the target product, high temperature (high energy consumption).

The objective of the invention is to obtain 2-ethyl-3,5-dimethylpyridine with a higher yield and at a lower temperature in comparison with known methods. This is achieved by the interaction of ammonia with propionic aldehyde in the presence of a catalyst for the crystalline hydrate of lanthanide nitrate Ln (NO ₃ ) ₃ · 6Н ₂ О (Ln = Pr, Nd, Tb) at a molar ratio of ammonia: aldehyde: catalyst equal to 50: 150: 1. The process is conducted at room temperature in dimethylformamide (DMF) for 24 hours.

The reaction proceeds according to the scheme.

Ln = Pr, Nd, Tb

Significant differences of the proposed method

In the proposed method, commercial lanthanide nitrate crystalline hydrate Ln (NO ₃ ) ₃ · 6H ₂ O (Ln = Pr, Nd, Tb) is used as a catalyst. The process is carried out at room temperature in DMF for 24 hours. The yield of the target product is 60-67%. In known methods, the reaction proceeds under the action of Co ₃ (PO ₄ ) ₂ or K ₂ O / Al ₂ O ₃ in the temperature range 350-450 ° C.

The proposed method has the following advantages:

1. The method allows to reduce the content of by-products of crotonic condensation of the aldehyde by lowering the interaction temperature and thereby increase the yield of the target product to 67%.

2. The method allows to significantly reduce the temperature (from 350-450 to 20 ° C) and thereby significantly simplify the synthesis and reduce the cost of the target product.

The method is illustrated by the following examples:

EXAMPLE 1. 81 mmol of propionic aldehyde is placed in a 25 ml glass flask mounted on a magnetic stirrer, cooled to 0 ° C, 27 mmol of ammonia are added, and stirred vigorously for 1-2 minutes, 0.54 mmol of Pr crystalline hydrate are added ( NO ₃ ) ₃ · 6H ₂ O and 5 ml of DMF and continue to mix for 24 hours at 20 ° C. The reaction mixture was extracted with ether (3 × 50 ml), the combined extracts were dried over anhydrous MgSO ₄ , the solvent was distilled off, and the residue was fractionated in vacuo. The yield of 2-ethyl-3,5-dimethylpyridine is 67% (2.44 g).

Other examples confirming the method are given in the table.

Example Catalyst Time h Exit, % Target product one Pr (NO ₃ ) ₃ · 6H ₂ O 24 67 2-ethyl-3,5-dimethylpyridine 2 Nd (NO ₃ ) ₃ · 6H ₂ O 24 64 2-ethyl-3,5-dimethylpyridine 3 Tb (NO ₃ ) ₃ · 6H ₂ O 24 60 2-ethyl-3,5-dimethylpyridine

All experiments were carried out in DMF at a molar ratio of ammonia: aldehyde: catalyst equal to 50: 150: 1 at 20 ° C.

The obtained 2-ethyl-3,5-dimethylpyridine has the following physicochemical characteristics:

2-ethyl-3,5-dimethylpyridine

¹³ C NMR spectrum 158.05 (C2), 129.59 (C3), 137.69 (C4), 129.39 (C5), 146.49 (C6), 17.09 (C7), 17.74 (C8), 27.51 (C9), 12.20 (C10).

¹ H NMR spectrum 1.25 (t, 3H, CH ₃ (10)), 2.21 (s, 6H, CH ₃ (7.8)), 2.46-2.88 (m, 2H, CH ₂ (9)), 7.15 (s , 1H, CH, (4)), 8.18 (s, 1H, CH, (2)).

Mass spectrum, (70 ev) m / z: 135 [M] ⁺ , 134, 120, 107, 91, 79, 77, 65, 53, 39.

Claims (1)

The method of obtaining 2-ethyl-3,5-dimethylpyridine of the General formula

by reacting ammonia with propionic aldehyde in the presence of a catalyst, characterized in that the catalyst used is crystalline hydrate of lanthanide nitrate Ln (NO ₃ ) ₃ · 6H ₂ O, where Ln is Pr, Nd and Tb, the molar ratio of reactants ammonia: aldehyde: catalyst is 50: 150: 1 and the process is carried out at room temperature in DMF for 24 hours.