N,N1-polimetilen bis morfolilo urea as a stimulant growth

The closest analogue in structure and properties is piperidine sol-4- [parachlorophenoxy butine acid as a cotton growth stimulator. The indicated substance piperidine salt (PS) of 4- [para-chlorophenoxy] -2-butynic acid is obtained: first, a Grignard reagent, then p-chlorophenol propargyl ester is added. The reaction mass is heated for 1.5 hours and cooled, the emitted carbon dioxide is passed through for 2 hours, then washed with an alkali solution, the alkaline solution is acidified, filtered and dried. Again, piperidine is added to the reaction mass in ether; a piperidine salt of 4- [para-chlorophenoxy] -2-butinoic acid forms a precipitate.

However, the synthesis of this substance is very difficult, due to the high toxicity of propargyl chloride involved in the synthesis, as well as its inaccessibility, since this substance is a scarce imported raw material. In addition, the synthesis of the growth stimulator is a multistage (6 stage) and a long process (8-9 hours).

Known drug N, N1-tetramethylene bis [(cyclohexyl) urea] and N, N-tetramethylene bis [(β-chloroethyl) urea] is obtained by reacting tetramethylene diisocyanate with cyclohexylamine (-H2N-CH2-CH2Cl) in 50% NaOH medium and triethylamine, the mixture is stirred for 7.5-8 hours, filtered, dried and cleaned, obtaining the following structural formulas:

NCN (CH 2 ) 6

HOH

NCN

I II I

HOH

CI CH 2 CH 2 N C N  (CH 2 ) 4 N C N CH 2 CH 2 CI

HOH   HOH

with yields of 62%. The authors then carry out the reaction of N-nitrosation in order to obtain anticancer activity [2-4]. However, the synthesis of this substance is very difficult due to the fact that the H2N-CH2-CH2Cl reagent is also a strong lacrimator that acts on the central nervous system, affects the liver, MPC 2 mg / l3. In addition, the synthesis of the above anticancer drug is a multistage (6 stages) long process (7.5 hours).

The purpose of this article is to reduce the stadial stage and the complexity of obtaining a growth stimulator, providing at very low concentration at a dilution of 750,000 times (0.00001% of the concentration compared to the known) growth-stimulating activity, reduction of toxicity, increasing the yield of the growth stimulator, as well as providing waste-free technology.

The task is achieved by obtaining N, N1-polymethylene bis [(morpholyl) urea] from hexane-1,6-diisocyanate in dimethylformamide and morpholine.

The mixture was kept at room temperature (28-340 ° C) for 3 hours. Then add water, the precipitated white precipitate is washed, chromatographed, dried, the melting point, the yield, the gross formula are determined.

Rostreguliruyuschuyu activity on tomato culture reaches 139.4% due to root growth at a concentration of 0.001% (Table 2.)

The task is achieved without waste-free technology for the synthesis of a new, first-produced low-toxic, environmentally friendly, easy way to obtain a growth stimulator that provides the growth-regulating properties of tomatoes, cucumbers, and cotton.

Waste-free technology for polymethylene bis [(morpholyl) urea]

17.4 g (0.2 mol) of morpholine are placed in a half-liter steel reactor, 30 ml of dimethylformamide are added and with vigorous stirring, 16.8 ml (0.1 mol) of hexane-1,6-diisocyanate are added dropwise. The reaction lasts for 2.5-3 hours at a temperature of 28-340 ° C. After the completion of the reaction, the contents of the reactor are transferred to the container, 150 ml of water is added. The precipitation is washed, dried at room temperature. Chromatographic on a column of AI2O3 II degree of purity. After drying, a white powder is obtained, the yield is 29.1 g (85.0%), T. pl. = 180 ° C; Rf = 0.69; molecular weight = 342.0.

Found%: C 55.75 H 8.44 N 16.03

Calculated for C16H30 N4O4,%: C 56.14 H 8.77 N 16.37

To prove the structure of the compound obtained, in addition to elemental analysis, IR spectra and molecular models were taken.

In the IR spectrum of polymethylene bis [(morpholyl) urea] there is a wide absorption band in the region of 1637 cm-1, characteristic for the HN-CO-N C = O bond absorption, the absorption band in the 3293 cm-1 region indicates the presence of NH groups, and finally for - (CH2) 6- groups in the 756-726 cm-1 region.

The data of elemental analysis and the IR spectrum, and molecular models confirm the structural formula of polymethylene bis [(morpholyl) urea].

To identify the growth-stimulating activity of polymethylene bis [(morpholine) urea], tests were carried out in the laboratory of the Institute of Chemistry of Plant Substances of the Academy of Sciences of the Republic of

Uzbekistan under laboratory conditions, biotests were seeds of vegetable crops and cotton.

In the experiments, cucumbers of the variety “Uzbekistan-740”, “Tempo” grade tomatoes and medium-fiber cotton, “S-6524” grade were used. The preparations were dissolved in DMFO and used by the method of presowing seed locking for 18-20 hours. Concentrations of 0.1 were used; 0.01; 0.001; 0.0001; 0.00001%. The repetition of experiments 4-fold. The counts were carried out by measuring the length of the stem and root in 10 day old seedlings of cotton.

It was noted that all drugs tend to stimulate the growth of the root systems of young seedlings, both vegetables and cotton.

Primary screening was carried out according to the method of Yu.V. Rakitin. This method allows you to quickly determine the degree of physiological activity of chemical compounds, which is detected by stimulating or inhibiting the germination of plant seeds, as well as by changing the length of the roots and the length of the stem part.

The preparations were tested by the method of locking seeds in solutions of different concentrations, followed by germination in Petri dishes. Control seeds were soaked in distilled water.

Each series of experiments is accompanied by control. In the control variants, only a pure solvent is added to the nutritional medium.

Comparative tests also show that the tested preparation is BC-2, i.e. Polymethylene bis [(morpholine) urea] from 7.5 to 75,000 times lower concentration of our drug, showed higher growth-stimulating activity than Roslin, which is now used in many sectors of agriculture in Uzbekistan.

BC-2 preparation on cotton culture showed biological activity, at a concentration of 0.00001% (in a separation of 75,000 times) stimulated root growth by 121.2%, and stem growth 114.3% above the control and the well-known drug Roslin (concentration 0.75-1.0%).

The BC-2 preparation on the cucumber culture also showed biological activity, at a concentration of 0.00001% (i.e., 75,000 times dilution) contributed to a root growth of 128.7%, slightly lower growth of the stem was 114.3% higher than the control and the famous drug "Roslyn".

The preparation BC-2 on tomatoes, similarly to the previous cultures, showed a very high biological activity, up to 117.1% at a concentration of 0.00001% (even in the division 75,000 times).

Thus, the low toxic (LD50 = 4070 mg / kg) preparation BC-2 did not show high stimulating properties on the seeds of tomato, cucumbers and cotton at 0.00001% concentration.

In conclusion, the BC-2 drug polymethylene bis [(morpholyl) urea] was synthesized using non-waste technology, even at a dilution 75,000 times several thousand times better than the stimulating activity of the currently used known drug Roslin and the control drug.

Information sources:

• [1]    - SU № 1453850, С 07 Д 295/02, 1988г.

• [2]    - патент 6133299 США, МПК⁷ А 61 К 31/44, заявл. 25.02.1993г., опубл. 17.10.2000г.

• [3]    - J. Med. Chem., 2001, 44, № 5, p. 694-702.

• [4]    - Rev. Roum. Chem., 1997, 22, № 6, p. 885-898.