PL191755B1 - Urea derivatives with thioether bridge and method of obtaining them - Google Patents

Abstract

1. Urea derivatives with a thioether bridge of the general formula 1, wherein R is a 4-chloroaniline, 4-bromoaniline, 4-methylaniline or 4-methoxyaniline group or an N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino or N,N-dibutylamino group. 2. A method for the preparation of urea derivatives with a thioether bridge of the general formula 1, wherein R is a 4-chloroaniline, 4-bromoaniline, 4-methylaniline or 4-methoxyaniline group or an N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino or N,N-dibutylamino group, characterized in that bis(isocyanatomethyl) sulfide is reacted with an aromatic amine of the general formula 2, wherein R1 is a 4-chloroaniline, 4-bromoaniline, 4-methylaniline or 4-methoxyaniline group or with an aliphatic N,N-dialkylamine of the general formula 3, wherein R2 is an N,N-dimethylamino, N,N-diethylamino group. N,N-dipropylamine or N,N-dibutylamine in a solution of an inert organic solvent, at room temperature in the case of aromatic amines and at a temperature lower than the boiling point of the aliphatic N,N-dialkylamine used, in an inert gas atmosphere.

Description

Description of the invention

The subject of the invention is new urea derivatives with a thioether bridge and a method for their preparation.

N-phenyldiureas and N, N-dialkyldiureas with a diethylene thioether group exhibiting insecticidal activity are known. These compounds are obtained by reacting bis (2-isocyanatoethyl) sulfide with ring substituted aniline derivatives or with aliphatic N, N-dialkylamines in an inert organic solvent solution under a nitrogen atmosphere.

The essence of the invention are new urea derivatives with a thioether bridge of the general formula I, in which R is 4-chloroaniline, 4-bromoaniline, 4-methylaniline or 4-methoxyaniline or N, N-dimethylamine, N, N-diethylamine, N, N -dipropylamine or N, N-dibutylamine. These N-phenyldiureas and N, N-dialkyldiureas compounds contain in the molecule a thioether bridge linked to methylene groups and two correspondingly substituted ureido groups.

Process for the preparation of urea derivatives with a thioether bridge of the general formula, in which R is 4-chloroaniline, 4-bromoaniline, 4-methylaniline or 4-methoxyaniline or N, N-dimethylamine, N, N-diethylamino, N, N-dipropylamine group or N, N-dibutylamino, where the bis (isocyanatomethyl) sulfide is reacted with an aromatic amine of the general formula 2, wherein R ¹ is 4-chloroaniline, 4-bromoaniline, 4-methylaniline or 4-methoxyaniline, or with an aliphatic N, N-dialkylamine of general formula 3, in which R ² is N, N-dimethylamino, N, N-diethylamino, N, N-dipropylamino or N, N-dibutylamino, in a solution of an inert organic solvent at a temperature at room temperature in the case of aromatic amines and at a temperature below the boiling point of the aliphatic N, N-dialkylamine used, under an inert gas atmosphere. Diethyl ether is used as the inert organic solvent and nitrogen is used as the inert gas.

The starting bis (isocyanatomethyl) sulfide is obtained by a Curtius rearrangement of the bis (azidocarbonylmethyl) sulfide in toluene solution. Bis (azidocarbonylmethyl) sulfide is obtained by nitrosation of bis (carbazoylmethyl) sulfide or by reaction of bis (chloroformylmethyl) sulfide with sodium azide.

The advantages of the method according to the invention are low raw material costs, simple technology and high product yields. The derivatives produced are characterized by a high degree of purity. The starting bis (isocyanatomethyl) sulphide is obtained by the phosgene-free method which does not pose any health or environmental hazards.

The compounds according to the invention showed insecticidal activity in preliminary and detailed tests carried out on a five-day-old imago of a female housefly.

The method according to the invention, without limiting its scope of protection, is presented in the following examples. IR spectra were recorded on a FT IR 2000 spectrophotometer, and ¹ H and ¹³ C NMR spectra were recorded on a Varian Gemini 200 spectrometer.

Example 1 To solutions of 1 g (0.0069 mol) of bis (isocyanatomethyl) sulfide in 30 ml of anhydrous diethyl ether, under an atmosphere of dry nitrogen, 0.017 mol of an aromatic amine is added with stirring, successively: 4-chloroaniline, 4-bromoaniline, 4-methylaniline (4-toluidine) or 4-methoxyaniline (4-anisidine). The reaction mixtures are then left for a dozen or so hours, filtered, washed several times with small amounts of cold room temperature, under nitrogen atmosphere, while stirring. The obtained deposits of N-phenyldiureas I-IV of diethyl ether, then crystallized from a mixture of methanol and dimethylformamide. Proceeding in this way, you get:

bis (4-chlorophenylureidomethyl) sulfide (I), m.p. 226.5-228 ° C and the cumulative formula C16H16Cl2N4O2S (MC 399.30).

Analysis: IR (KBr, cm ^-1 ): 3310, 1561 (NH), 2989, 2918 (CH alif), 1631 (C = O), 1228 (CN), 631 (CS); ¹ H NMR (TMS, DMSO-d6, 6 ppm): 4.37 (d, 4H, CH2), 6.86 (t, 2H, _CH? NH), 7.26, 7.43 (AA'BB ' , 8H, CH arom), 8.96 (s, 2H, arom CNH); ¹³ C NMR (TMS, DMSO-D6, 8 ppm): 39.67 (2C, CH2S), 118.50, 127.40 (8C, CH arom), 123.99 (2C, CCl arom), 138 , 04 (2C, arom CN), 153.71 (2C, CO);

bis (4-bromophenylureidomethyl) (II) sulfide, m.p. 234-235 ° C and the cumulative formula C16H16Br2N4O2S (MC 488.20).

Analysis: IR (KBr, cm ^-1 ): 3311, 1555 (NH), 2922 (CH alif.), 1634 (CO), 1228 (CN), 637 (CS); ¹ H NMR (TMS, DMSO-D6, d ppm): 4.38 (d, 4H, CH2S), 6.87 (t, 2H, CH2NH), 7.38 (m, 8H, CH arom), 8 , 96 (s. 2H, arom CNH); ¹³ C NMR (TMS, DMSO-D6, d ppm): 40.52 (2C, CH2S), 112.67 (2C, CBr arom), 119.80, 131.20 (8C, CH arom), 139 , 36 (2C, arom CN), 154.57 (2C, CO);

PL 191 755B1 bis (4-methylphenylureidomethyl) (III) sulfide, m.p. 218-219.5 ° C and the cumulative formula C18H22N4O2S (MC 358.47).

Analysis: IR (KBr, cm ^-1 ): 3315, 1562 (NH), 2920, 2863 (CH alif.), 1635 (C = O), 1232 (CN), 634 (CS); ¹ H NMR (TMS, DMSO-D6, 8 ppm): 2.20 (s, 6H, CH3), 4.38 (d, 4H, CH2S), 6.76 (t, 2H, CH2NH), 7.02 , 7.28 (AA'BB ', 8H, CH arom), 8.68 (s, 2H, arom CNH); ¹³ C NMR (TMS, DMSO-D6, d ppm): 20.02 (2C, CH3), 40.51 (2C, CH2S), 118.04, 128.77 (8C, CH arom), 130.06 (2C, CCH3 arom), 137.31 (2C, arom CN), 154.74 (2C, CO);

bis (4-methoxyphenylureidomethyl) (IV) sulfide, m.p. 215-216.5 ° C and the cumulative formula C18H22N4O4S (MC 390.46).

Analysis: IR (KBr, cm ^-1 ): 3325, 1551 (NH), 2926, 2839 (CH alif.), 1636 (C = O), 1236 (CN), 620 (CS); ¹ H NMR (TMS, DMSO-D6, d ppm): 3.68 (s, 6H, CH3O), 4.37 (d, 4H, CH2S), 6.71 (t, 2H, CH2NH), 6.81, 7.30 (AA'BB ', 8H, CH arom), 8.60 (s, 2H, arom CNH); ¹³ C NMR (TMS, DMSO-D6, d ppm): 40.55 (2C, CH2S), 55.05 (2C, CH3O), 113, 80, 119.76 (8C, CH arom), 133.01 (2C, arom CN), 154.19 (2C, COCH3 arom), 154.93 (2C, CO).

Example II. To solutions of 1 g (0.0069 mol) of bis (isocyanatomethyl) sulfide in 30 ml of anhydrous diethyl ether, under an atmosphere of dry nitrogen, 0.028 mol of aliphatic N, N-dialkylamine, N, N-dimethylamine, N are added while stirring. , N-diethylamine, N, N-dipropylamine or N, N-dibutylamine. When using N, N-dimethylamine, the reaction is carried out at temperature

-5 ° C. The resulting suspensions are stirred for several hours at room temperature under nitrogen atmosphere, with the exception of the synthesis of V diurea, where the temperature of the reaction mixture is kept at 0 ° C to -5 ° C. The solvent and excess aliphatic N, N-dialkylamines are then distilled off using a rotary evaporator under reduced pressure. Attempts to crystallize the obtained derivatives V-VIII from water, methanol, ethanol and mixtures of methanol or ethanol with water proved ineffective and N, N-dialkyldiureas V-VIII were obtained in the form of an amorphous solid (compound V) or thick, oily liquids (compounds VI-VIII). By doing so, you get:

bis (N, N-dimethylureidomethyl) (V) sulfide, m.p. 59-61 ° C and the cumulative formula C8H18N4O2S (MC 234.32).

IR analysis (KBr, cm ^-1 ): 3331, 1528 (NH), 2936 (CH alif.), 1618 (C = O), 1225 (CN), 669 (CS); ¹ H NMR (TMS, CDCl3, d ppm): 2.91 (s, 12H, CH3), 4.44 (d, 4H, CH2), 6.13 (broad band, 2H, NH); ¹³ C NMR (TMS, CDCl3, δ ppm): 36.16 (4C, CH3), 42.90 (2C, CH2S), 158.23 (2C, CO);

Bis (N, N-diethylureidomethyl) sulfide (VI) as a thick, oily liquid with the cumulative formula C12H26N4O2S (MC 290.43).

Analysis: IR (film, cm ^-1 ): 3332, 1527 (NH), 2975, 2933 (CH aliph.), 1633 (C = O), 1272 (CN), 670 (CS); ¹ H NMR (TMS, CDCl 3, 5 ppm): 1.12 (t, 12H, CH3), 3.25 (qui, 8H, CH3CH2), 4.45 (d, 4H, CH2S), 6.06 (t , 2H, NH); ¹³ C NMR (TMS, CDCl, d ppm): 13.71 (4C, CH 3), 41.03 (4C, CH3CH2), 42.26 (2C, CH ₂ S), 157.10 (2C, CO); Bis (N, N-dipropylureidomethyl) sulfide (VII) as a thick oily liquid with the cumulative formula C16H34N4O2S (MC 346.54).

Analysis: IR (film, cm ^-1 ): 3328, 1526 (NH), 2961, 2877 (CH aliph.), 1634 (C = O), 1247 (CN), 673 (CS); ¹ H NMR (TMS, CDCl, d ppm): 0.90 (t, 12H, CH 3), 1.55 (m, 8H, CH3CH2), 3.13 (m, 8H, CH3CH2CH2), 4.45 (d , 4H, CH2S), 5.88 (t, 2H, NH); ¹³ C NMR (TMS, CDC13, 8 ppm): 11.14 (4C, CH3), 21.66 (4C, CH3CH2), 41.51 (2C, CH2S), 48.87 (4C, CH3CH2CH2), 157, 44 (2C, CO);

Bis (N, N-dibutylureidomethyl) sulfide (VIII) as a thick, oily liquid with the total formula C20H42N4O2S (MC 402.65).

Analysis: IR (film, cm ^-1 ): 3332, 1527 (NH), 2956, 2935, 2870 (CH alif.), 1635 (C = O), 1231 (CN), 673 (CS); ¹ H NMR (TMS, CDCl, d ppm): 0.90 (t, 12H, CH 3), 1.30 (sxt, 8H, CH3CH2), 1.32 (m, 8H, CH3CH2CH2), 3.16 (qui , 8H, CH3CH9CH2CH2), 4.44 (d, 4H, CH2S), 5.91 (t, 2H, NH); ¹³ C NMR (TMS, CDCl3, d ppm): 13.77 (4C, CH3), 20.07 (4C, CH3CH2), 30.67 (4C, CH3CH9CH2CH2), 41.34 (2C, CH2S), 46, 95 (4C, CH3CH2CH2CH2), 157.36 (2C, CO).

The insecticidal activity of the new urea derivatives I-VIII was assessed on the basis of a preliminary test carried out in laboratory conditions. As a bioindicator, a five-day-old imago of a female housefly was used - Musca domestica L. Each of the tested compounds was used in the solution at the following concentrations: 0.1%, 0.01% and 0.001%. N-Phenyldiureas I-IV were used as solutions in dimethylformamide, and N, N-dialkyldiureas V-VIII as solutions in ethanol.

On the surface of Petri dishes with a diameter of 10 cm, 1 ml of the prepared solutions was applied with a pipette in a spiral motion to each lower and upper dish. For the control object used

PL 191 755B1 solvent only. During the inspection, all undesirable factors that could have influenced the test results, including natural insect mortality, were eliminated. The control insects were subjected to the same treatments as the insects with the tested preparations. After evaporation of the solvent, 10 five-day-old imago of a female housefly were placed in each of the lower plates. The insects were anesthetized with carbon dioxide. Then the plates were covered and kept in an air-conditioned room at 25 ° C.

The assessment of the insecticidal activity of the tested compounds was performed after 24 hours, and then after 29 hours from the start of the experiment, after these periods the percentage of insect mortality was determined, which is the effectiveness of the preparations. Insects treated with individual compounds were compared each time with insects from the control object. The assessment was carried out according to a five-point scale, in which, based on the percentage of insect mortality, the following were assumed:

over 90% - very good effect of the preparation,

-90% - good effect of the preparation,

- 70% - medium effect of the preparation,

-40% - poor effect of the preparation, below

20% - very poor effect of the preparation.

The experiment was carried out in triplicate for each of the given concentrations, and the results presented are the mean of triplicate. The obtained results are summarized in the table.

Tabe la

No. of diurea Insect mortality, [%] after 24 hours after 29 hours AND II - - III 40-45 56-60 IV 46 65 V 38-48 54 VI 45-50 70 VII 40-45 55-65 VIII 50 60-64

Only N-phenyldiureas III and IV, containing no chlorine or bromine atom in the aromatic rings, showed moderate insecticidal activity. Preparations I and II with a chlorine or bromine atom in the aromatic rings showed no insecticidal activity against the house fly. All V-VIII N, N-dialkiI diureas showed moderate insecticidal activity.

Claims (3)

Patent claims 1. Urea derivatives with a thioether bridge of the general formula, in which R is 4-chloroaniline, 4-bromoaniline, 4-methylaniline or 4-methoxyaniline or N, N-dimethylamine, N, N-diethylamine, N, N-dipropylamine, or N, N-dibutylamine. 2. Process for the preparation of urea derivatives with a thioether bridge of the general formula, in which R is 4-chloroaniline, 4-bromoaniline, 4-methylaniline or 4-methoxyaniline or N, N-dimethylamino N, N-diethylamino N, N-dipropylamino or N, N-dibutylamine, characterized in that the bis (isocyanatomethyl) sulfide is reacted with an aromatic amine of the general formula II in which R ¹ is 4-chloroaniline 4-bromoaniline 4-methylaniline or 4-methoxyaniline or with N, N -dialkiloaminą aliphatic radical of the general formula 3, wherein R ² is an N, N-dimethylamino, N, N-diethylamino. N, N-dipropylamine or N, N-dibutylamine in an inert organic solvent solution at room temperature PL 191 755B1 for aromatic amines and at a temperature below the boiling point of the aliphatic N-dialkylamine used under an inert gas atmosphere. 3. The method according to p. The process of claim 2, wherein the inert organic solvent is diethyl ether and the inert gas is nitrogen.