RU2334739C1 - Method of 2,3,5-trialkylpyridines production - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention refers to heterocycle production methods, specifically to technology of 2,3,5-trialkylpyridines. Substance of method consists in catalytic reaction of ammonia with aliphatic aldehydes with lanthanide trichloride crystalline hydrate LnCl₃·6H₂O (Ln=Pr, Nd, Tb) at molar ratio ammonia: aldehyde: catalyst equal to 50:150:1, process is performed at atmospheric pressure, room temperature, in dimethyl sulfoxide within 24 h in air atmosphere. These compounds are widely used for synthesis of medical products, including anti-HIV agents, and for production of pigment, plant chemical protection products, as extracting agents, sorbents and corrosion inhibitors.

EFFECT: by-product content reduction, higher yield of end product, end product cost saving.

1 tbl, 1 ex

Description

The present invention relates to methods for producing heterocyclic compounds, specifically to a method for producing 2,3,5-trialkylpyridines of the general formula

where R = C ₂ H ₅ , C ₃ H ₇ , C ₄ H ₉

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, plant protection products, as extractants, sorbents and corrosion inhibitors.

The known method (Yu.D.Dolskaya, G.Ya. Kondratyev. Catalytic synthesis of alkylpyridines from 2-azarlenes-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-propylidenepropenylamine with propylene under the action of a heterogeneous catalyst composition K ₂ O / Al ₂ O ₃ at a temperature of 410-450 ° C.

The disadvantages of this method include the low yield of the target product (17%), high temperature (high energy consumption), and the inaccessibility of N-propylidenepropenylamine (the synthesis is carried out by the reaction of propionic aldehyde with allyl (or propenyl) amine at 410-450 ° C).

The known method (F.A. Selimov, A.Zh. Akhmetov, U.M. Dzhemilev. Synthesis of alkyl substituted pyridines by liquid-phase condensation of aldehydes with amines under the influence of metal complex catalysts. Izv. AN SSSR, Ser. Chem., 1987, No. 9, 2042 ) obtaining 2,3,5-trialkyl-substituted pyridines in the reaction of liquid-phase condensation of aliphatic aldehydes with urea under the action of the Co (2-ethylhexanoate) ₂ -Et ₃ Al catalyst system. The yield of 2,3,5-trialkylpyridines reaches 80% during the reaction 4 hours, at 200 ° C, in benzene, in an argon atmosphere.

The disadvantages of this method include high energy consumption (high temperature, pressure), the need to use special equipment (autoclave), argon, fire, explosive Et ₃ Al, as well as the need for preliminary obtaining complex Co (2-ethylhexanoate) ₂ .

A new method is proposed for producing 2,3,5-trialkylpyridines.

The essence of the method consists in the interaction of ammonia with aliphatic aldehydes in the presence of a catalyst for crystalline lanthanide trichloride LnCl ₃ · 6H ₂ O (Ln = Pr, Nd, Tb) with a molar ratio of ammonia: aldehyde: catalyst equal to 50: 150: 1. The process is conducted in air, at atmospheric pressure and room temperature in Limethyl sulfoxide (DMSO) for 24 hours.

The reaction proceeds according to the scheme:

R = C ₂ H ₅ , C ₃ H ₇ , C ₄ H ₉ ; Ln = Pr, Nd, Tb

Significant differences of the proposed method

1. In the proposed method, a commercial crystalline hydrate of lanthanide trichloride LnCl ₃ · 6H ₂ O (Ln = Pr, Nd, Tb) is used as a catalyst. The process is conducted in air at atmospheric pressure and room temperature in DMSO for 24 hours. The yield of the target products reaches 83%. In known methods, K ₂ O / Al ₂ O ₃ or less available compounds are used as a catalyst: a complex of Co (2-ethylhexanoate) ₂ and Et ₃ Al. The process is conducted in the range of 200-420 ° C.

The proposed method has the following advantages.

1. As a catalyst, crystalline hydrates LnCl ₃ · 6H ₂ O (Ln = Pr, Nd, Tb) produced by domestic industry are used.

2. The method allows, by reducing the interaction temperature, to reduce the content of by-products of the croton condensation of the aldehyde and thereby increase the yield of the target product to 83%.

3. The method allows to significantly reduce the temperature (from 200-420 to 20 ° C), does not require special equipment (autoclave), argon atmosphere and thereby significantly simplifies the synthesis and reduce the cost of the target product.

The method is illustrated by the following examples.

EXAMPLE 1. 81 mmol of butyric 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 NdCl ₃ · trichloride crystalline hydrate is added 6H ₂ O and 5 ml DMSO and continue to stir for 24 hours at 20 ° C. The reaction mass is extracted with ether (3 × 50 ml), the combined extracts are dried over anhydrous MgSO ₄ , the solvent is distilled off and the residue is fractionated in vacuo. The yield of 2-propyl-3,5-diethylpyridine is 81% (3.87 g).

Other examples confirming the method are given in the table.

Table Example Aldehyde Catalyst Exit, % Target product one Oil
C ₄ H ₈ O NdCl ₃ · 6H ₂ O 81 2-Propyl-3,5-diethylpyridine 2 Oil
C ₄ H ₈ O PrCl ₃ · 6H ₂ O 83 2-Propyl-3,5-diethylpyridine 3 Oil
C ₄ H ₈ O TbCl ₃ · 6H ₂ O 61 2-Propyl-3,5-diethylpyridine four Valerian
C ₅ H ₁₀ O PrCl ₃ · 6H ₂ O 77 2-butyl-3,5-dipropylpyridine 5 Kapron
C ₆ H ₁₂ O PrCl ₃ · 6H ₂ O 74 2-amyl-3,5-dibutylpyridine

All experiments were carried out in DMSO with a molar ratio of ammonia: aldehyde: catalyst equal to 50: 150: 1, at 20 ° C for 24 hours.

The resulting compounds have the following physicochemical characteristics:

2-Propyl-3,5-ethylpyridine. T _bale 75-78 ° C (1 mmHg).

Found,%: C 81.92; N, 7.83; H, 10.25. C ₁₂ H ₁₉ N.

Calculated,%: C 81.35; N, 7.92; H, 10.73.

¹ H NMR Spectrum (CDCl ₃ , δ, ppm): 0.98 m (3H, CH ₃ ); 1.18 m (6H, CH ₃ ); 1.32 m (2H, CH ₂ ); 2.54-2.66 m (4H, CH ₂ ; 2.72 q (2H, CH ₂ ); 7.25-8.21 d (2H, C ₅ H ₂ N).

¹³ C NMR spectrum (CDCl ₃ , δ, ppm): 14.06 k (C ¹³ ); 14.70 k (C ¹¹ ); 15.19 k (C ⁹ ); 22.79 t (C ¹² ); 24.89 t (C ⁸ ); 25.47 t (C ¹⁰ ); 36.30 t (C ⁷ ); 135.29 d (C ⁴ ); 136.07 s (C ³ ); 136.36 s (C ⁵ ); 145.83 d (C ⁶ ); 157.04 s (C ² ).

2-Butyl-3,5-propylpyridine. T _bale 80-82 ° C (1 mmHg).

Found,%: C 81.93; N 6.52; H, 11.55. C ₁₅ H ₂₅ N.

Calculated,%: C 82.19; N, 6.39; H, 911.42.

¹ H NMR Spectrum (CDCl ₃ , δ, ppm): 0.90 m (9H, CH ₃ ); 1.40 m (2H, CH ₃ ); 1.53 m (6H, CH ₂ ); 2.53 m (4H, CH ₂ ); 2.63 m (2H, CH ₃ ); 7.17-8.15 d (2H, C ₂ H ₅ N).

¹³ C NMR spectrum (CDCl ₃ , δ, ppm): 13.11 q (C ¹⁶ ); 13.60 c (C ¹³ ); 14.25 k (C ¹⁰ ); 22.90 t (C ¹⁵ ); 23.31 t (C ¹² ); 24.23 t (C ⁹ ); 25.07 t (C ¹⁴ ); 28.63. t (C ⁸ ); 31.46 t (C ¹¹ ); 34.30 t (C ⁷ ); 133.23 d (C ⁴ ); 135.54 s (C ³ ); 136.82 s (C ⁵ ); 141.47 d (C ⁶ ); 158.10 s (C ² ).

2-Amyl-3,5-dibutylpyridine. T _bale 105-108 ° C (1 mmHg).

Found,%: C 82.27; N, 5.80; H, 11.93. C ₁₈ H ₃₁ N.

Calculated,%: C 82.76; N, 5.36; H, 11.88.

¹ H NMR Spectrum (CDCl ₃ , δ, ppm): 0.92 m (9H, CH ₃ ); 1.32 m (14H, CH ₂ ; 2.50 m (4H, CH ₂ ); 2.70 m (2H, OD); 7.10-8.20 d (2H, C ₅ H ₂ N).

¹³ C NMR spectrum (CDCl ₃ , δ, ppm): 13.07 k (C ¹⁹ ); 13.07 k (C ¹⁵ ); 14.11 k (C ¹¹ ); 22.26 t (C ¹⁸ ); 22.26 t (C ¹⁴ ); 22.49 t (C ¹⁰ ); 28.40 t (C ⁸ ); 30.44 t (C ¹² ); 32.64 t (C ¹⁷ ); 32.87 t (C ⁹ ); 33.01 t (C ¹³ ); 33.52 t (C ¹⁶ ); 34.56 t (C ⁷ ); 135.22 d (C ⁴ ); 136.28 s (C ³ ); 136.55 s (C ⁵ ); 145.89 d (C ⁶ ); 159.06 s (C ² ).

Claims (1)

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

where R is C ₂ H ₅ , C ₃ H ₇ , C ₄ H ₉ , consisting in the interaction of ammonia with aliphatic aldehydes of the general formula RCH ₂ CHO, where R has the above meanings, in the presence of a catalyst for crystalline lanthanide trichloride LnCl ₃ · 6H ₂ O (Ln - Pr, Nd, Tb) at a molar ratio ammonia: aldehyde: catalyst, equal to 50: 150: 1, atmospheric pressure, room temperature, in DMSO, for 24 hours in an atmosphere of air.