CS202432B1 - Method of preparing ethylene-n,n-bis-valine - Google Patents

Description

The present invention relates to the preparation of ethylene-Ν, Ν'-bis-valine.

Ethylene-Ν, Ν'-bis-valine is a novel complexone based on the natural amino acid valine.

It is a newly synthesized substance, not yet described in the literature. Although there are some lower amino acid condensation data in the patent literature (British Patent No. 723,316), the disadvantage of this process is that it is operated under pressure and the reaction yields are relatively low.

The present invention is directed to the preparation of a novel complexone, ethylene-Ν, Ν'-bis-valine, by condensation, preferably in an alkaline medium, of valine with ethylene dihalide, wherein the molar ratio of amino acid to ethylene dihalide is 2: 1 to 5: 1. 1.10® pressure Pa to 5.10® Pa, preferably from 1.10 to ⁵ Pa 5.10®. Condensation is carried out in an aqueous environment.

The condensation of valine with ethylenedihalide follows the equation,

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CH-CH-COOH + 2

AND

NH

AND

NH

CH-CH-COOH where X = halogen.

The reaction produces ethylene-Ν, Ν'-bia valine and a hydrogen halide, which is preferably bound by the addition of alkali in the form of the corresponding alkali metal halides, thereby moving the reaction to the right, favoring the formation of ethylene-Ν, Ν'-bis- valine.

Condensation in aqueous media is carried out by mixing an aqueous solution of valine with ethylene dihalide and an aqueous or aqueous-alcoholic / resp. an alcoholic / alkali metal hydroxide solution. Also preferred is the use of solid alkali metal or alkaline earth metal carbonate or bicarbonate. The solution was refluxed for several hours with stirring.

After cooling the solution and acidifying with an inorganic acid, preferably concentrated hydrochloric acid, the crude ethylene-Ν, Ν -his-valine precipitates, which is recrystallized several times from hot water and the resulting crystalline material is dried under vacuum.

An advantage of the preparation of the ethylene-N, N'-biavaline according to the invention is that the condensation proceeds sufficiently quickly already at atmospheric pressure and with higher yields than the processes described in the above-mentioned patent.

The new valine-based complexone could find use in analytical chemistry as a metal-determining agent, in catalysis in redox reactions and in the medical field as a selective datoxifying agent.

Prlkladprovedenl

In a 250 ml three-necked flask equipped with a michadioma, a reflux condenser and a dropping funnel, 20 g (0.5 mol) of NaOH in 40 ml of water was added to 58.5 g (0.5 mol) of L-valine. The solution is heated with stirring to reflux and 47 g / 0.25 mole / of ethylene together with 34.5 g / 0.25 mol / ^K 2 ^C0 3 P ⁸⁶ ° ^Malu added so that the pH of the solution was in the range of 10 to 11 After all ethylene dibromide was added and the solution was allowed to reflux for 20 hours with stirring. Upon cooling and acidification with concentrated HCl to pH 8, a white crude product precipitated which, after washing with distilled water, was recrystallized several times from hot water and the crystals obtained were dried in vacuo. 40 g of ethylene-Ν, Ν'-bis-L-valine are obtained, which is 81.5% yield. Melting point 281 ° C (carbon monoxide). The overall formula is 12 12 ^ 24 ^W 2 ° 4 * ^{Molecular Mass} 280.3. Elemental analysis: Calculated: 55.40 λ C, 9.21 XH, 10.73 X N. Found: 55.69 XC, 9.16 XH, 10.67 X N. The newly synthesized substance obtained was characterized by IR and 1 H. -NMR spectroscopy

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IR spectra were measured by KBr technique. The characteristic absorption bands of ethylene-Ν, Ν-bie-L-valine bonds are shown in Table 1.

Table 1

Belt position

/ cm ¹ / Characteristics Note 3400 mr ^ ₂ ⁺ vatlenční vibrace 2860 - 3100 = CH ₃ ⁺ H _2% * ^ CH valence vibrations 1590 deformation vibrations 1575 -0 ⁱⁿ asC00 valence Vibration 1430 - 1470 ch ₂ scissoring vibration 1305 ^ sCOO valence vibrations 1320 ch ₂ wagging vibration 1250-1260 ^ COH deformation vibrations 1100 - 1200 rocking vibration 1055 ^ C-N valence vibrations 770 ^ C-C valence vibrations 545 nh ₂ ⁺ torsional vibration

The structure of the new compound was confirmed by 1 H-NMR spectroscopy. The ethylene-N'-bis-L-valine solution was prepared at a concentration of 10% by weight. in D ₂ ° P ° alkalization to pH approx. 12 with KOD. Sodium salt of 3- (trimethylsilyl) propionic acid (TSP) was used as internal standard. Spectra were measured at an operating frequency of 80 MHz. The resonant frequencies of the individual signals together with their integral intensities are shown in Table 2.

Table 2

"Exp" theor

Assigned

S, ppm (R)

226.0

220.0

204.5 155.8 '146.7 140.0 ► 134.0

128.6 ^r z

1.9

4.0

-CH "

2.8> N-CH ₂ -CH ₂ -N <

2.5

CH,

1.0 2 -CH * ch ₃

1,8

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77.0 75.8 70.3 68.0 ₍

12.1 12

CH ³ I -CH ² y ch

0.9 * In the case of a multiplet, it corresponds to the center of the bands.

Claims (1)

A process for the preparation of ethylene-Ν,--bis-valine, characterized in that valine is condensed with ethylenedihalide, preferably and ethylenedibromide, in an alkaline medium at reflux and in a pressure range of from 1.10 to 5.10 Pa, preferably to 1.10. up to 5.10 Pa, in a 2: 1 to 5: 1 valine: ethylene dihalide molar ratio, wherein the acidic reaction and the inorganic acid, preferably concentrated hydrochloric acid, isolate the crude product which is purified by recrystallization.