CS366491A3 - Process for preparing n-monosubstituted or n,n'-disubstituted urea - Google Patents

Abstract

Process for the preparation of N-mono- or N,N-disubstituted ureas by reacting ammonium isocyanate with a primary or secondary amine in a diluent.

Description

1

Production method N-monosubstituted or N, N-disubstituted

T urea

Technical field

The present invention relates to a process for the preparation of N-or N, N-disubstituted urea. u ·> "> oστ- α- i,> '> m o f1 1 - 5 Z? 3 q n axis b 41 i t u u.

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BACKGROUND OF THE INVENTION The preparation of N-monosubstituted or N, N-disubstituted urea derivatives by reacting isocyanic acid released, for example, by addition of an acid to a potassium isocyanate or sodium, with primary or secondary amines is generally known in the art of Houben-Weyl. , Methodender organischem Chemie, Erweiterungs- und Folgebánde zuřvierten Auflage, Vol. E4, pp. 362-364. An example of this reaction has been disclosed in Organic Synthesis, Vol. 31, 1951, pp. 9-11, the reaction of p-bromoaniline with sodium isocyanate in a mixture of glacial acetic acid and water to form p-bromophenylurea is described. In European Patent Specification. 333,350 discloses the production of aromatic bis-di-alkylurea derivatives by reacting an aromatic diamine with isocyanate, liberated by acidification of potassium, sodium or silver isocyanate.

SUMMARY OF THE INVENTION

It has now been found that primary or secondary amines can be reacted not only with isocyanate but also with its salts, in particular ammonium isocyanate, to obtain N-monosubstituted or N, N-disubstituted urea derivatives. Unexpectedly, the process may be carried out such that it is not necessary to release the isocyanate acid from the isocyanate ammonium by acid treatment. 2

Accordingly, the present invention provides a process for preparing an N-monosubstituted or N, N-disubstituted urea by reacting an ammonium isocyanate in a diluent with a primary or secondary amine.

Ammonium isocyanate is formed, for example, by rapid evaporation of the urea followed by condensation of the reaction gases, for example, according to U.S. Pat. No. 2,712,491, or by spraying molten urea into ammonia gas at high temperatures followed by condensation of the reaction mixture, e.g., U.S. Patent No. 2,712,492.

The term "primary or secondary amines" refers to compounds which contain one or more amino groups. They may be substituted with additional, inert groups under the reaction conditions. Examples are aliphatic, cycloaliphatic or cyclic amines, for example methylamine, ethylamine, hexylamine, hexadecylamine, isopropylamine, isobutyl amine, isooctylamine, methylethylamine, cyclohexylamine, pyrrolidine, pyrrole, piperidine, morpholine, dimethylamine, diethylamine, diisopropylamine, ethylenediamine hexamethylenediamine, 4,4'-diaminodicyclohexylmethane or aromatic amines such as aniline, nitroanilines, chloranilines, tollylamines, benzylamines, naphthylamines, phenylenediamines, tolluylenediamines, 4,4'-diaminodiphenylmethane and others. To carry out the process of the present invention, isocyanate ammonium is used as a precursor in a diluent which is inert to the reaction conditions and then a primary or secondary amine is added with stirring, or a primary or secondary amine is used as a diluent inert under the reaction conditions. or without diluent when the amine is liquid and can simultaneously serve as a diluent, and ammonium isocyanate is added with stirring.

As the inert diluent, for example, aliphatic hydrocarbons such as pentane, hexane, heptane, aromatic hydrocarbons such as benzene, toluene, xylene, halogenated aliphatic hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, ethyl chloride, ethylene chloride, halogenated aromatic hydrocarbons, can be used. as chlorobenzene, tri-chlorobenzenes, ethers such as diethyl ether, diisopropyl ether, dibutyl ether, ethyl methyl ether, dioxane, tetrahydrofuran, dimethoxyethane, carboxylic acid amides such as dimethylformamide, N-methylpyrrolidone, alcohols such as methanol, ethanol, diisopropyl alcohol and also water or mixtures of said solvents. Preference is given to the use of aliphatic or aromatic hydrocarbons, halogenated aliphatic or aromatic hydrocarbons, ethers, alcohols and water, particularly preferred is n-hexane, chloroform, chlorobenzene, dioxane and water.

Ammonium isocyanate can be added as such or with a diluent which is inert under the reaction conditions, for example together with any of the aforementioned liquid diluents, the primary or secondary amine being added as such in gaseous or liquid form or together with an inert diluent under reaction conditions, for example, together with any of the above gaseous or liquid diluents. The addition can be carried out at temperatures ranging from -20 ° C to the boiling point of the diluent used, preferably at -10 ° C to room temperature, particularly preferably at room temperature.

Amine can be added to the ammonium isocyanate in an equivalent amount or excess. It may also be expedient to add ammonium isocyanate in excess to accelerate the reaction. Usually, however, except where the amine serves as a diluent, the amine is reacted with isocyanate-ammonium in equivalent amounts. 4

After the addition of the amine or isocyanate ammonium is complete, the reaction mixture is further stirred to complete the reaction at a temperature that can reach the reflux temperature of the reaction mixture, but preferably the reaction is first carried out at room temperature and then refluxed. Alternatively, the reaction can be carried out using elevated pressure, for example up to 2.0 mPa.

After cooling, the obtained compound crystallizes out of the diluent and is filtered off without the need to evaporate the diluent and optionally the volatile components of the reaction mixture. Alternatively, the reaction product can be purified by conventional means such as recrystallization, distillation or chromatography. When urea is formed as a by-product, which can occur, urea can be precipitated as a solid, depending on the diluent used, and optionally removed by filtration, recrystallization or chromatography.

In a preferred embodiment of the process of the invention, the isocyanatammonium salt is dissolved or suspended in a diluent which is inert under the reaction conditions and then an equivalent amount of a primary or secondary amine diluted with the same solvent is added with stirring to the room. After the addition is complete, the mixture is stirred at room temperature to quench the reaction and heat to the boiling point of the solvent under reflux. After cooling the reaction mixture, the precipitate formed is filtered off with suction and optionally recrystallized. When using water as a diluent, the reaction product can be recrystallized directly from the reaction mixture after dilution with water. If no precipitate is formed after completion of the reaction, the solvent can be evaporated and the evaporate evaporated and optionally recrystallized or chromatographed. In another preferred embodiment, the liquefied primary or secondary amine is used at room temperature as both the reactant and the diluent and ammonium isocyanate is added with stirring.

After the addition is complete, the reaction mixture is stirred at room temperature for the completion of the reaction and then at elevated temperature. After completion of the reaction, the amine is distilled off or removed by chromatography and the product thus obtained is further purified by crystallization and recrystallization or chromatography.

The process of the invention allows for the simple obtaining of N-moosubstituted or N, N-disubstituted urea from ammonium isocyanate in good yield and therefore represents technical advances.

The invention will now be described in more detail with reference to the following non-limiting Examples. EXAMPLE 1 10.8 g (0.15 mol) of 83% ammonium isocyanate are brought to a suspension in 90 ml of chloroform, 28.1 g, 0.15 mol of dodecylamine dissolved in chloro is added at room temperature. forma ,. the mixture was stirred for 1 hour and then heated at reflux for 2 hours. After cooling, the precipitate formed is filtered off with suction and dried. In this way, 33.5 g of dodecylurea having a melting point of 102 DEG-105 DEG C. are obtained in a yield of 98% of theory. Example 2

The procedure described in Example 1 was followed, but 14.9 g (0.15 mol) of cyclohexylamine was used instead of dodecylamine, yielding 20.1 g of cyclohexylurea in 94% of theory.

Analysis calculated for C 59.1, H 9.9, N 19.7%, found C 59.2, H 9.9, N 19.7%. Example 3

The procedure described in Example 1 was followed but the isopropylamine (8.9 g, 0.15 mol) was used instead of dodecylamine to give 13.7 g of isopropylurea in 89% of theory.

H, 9.8; N, 27.2. Found: C, 47.0; H, 9.6; N, 27.7%. 7 Example 4

The procedure described in Example 1 is followed, but 4.5 g (0.075 mol) of ethylenediamine is used instead of dodecylamine to yield 6.1 g of ethylenediurea in 55% of theory.

Analysis calculated for C 32.7, H 6.9, N 38.1%, found C 32.7, H 7.0, N 38.2%. Example 5

The procedure described in Example 1 was followed but 14.0 g (0.15 mol) of aniline was used instead of dodecylamine and water was used instead of chloroform. The reaction was recrystallized directly from the reaction mixture by addition of water. 4.9 g of phenylurea with a melting point of 145 DEG-148 DEG C. are obtained in this way in a yield of 24% of theory. Example 6

The procedure described in Example 1 was followed but 14.0 g (0.15 mol) of aniline was used instead of dodecylamine to give 7.6 g of phenylurea (37% of theory, m.p. 145-148 ° C). EXAMPLE 7 18.6 g (0.2 mol) of aniline are reacted with 13.3 g (0.2 mol) of 90% ammonium isocyanate under stirring at room temperature. The reaction mixture was stirred at room temperature for 1 hour and then stirred for 5 hours at 55-60 ° C. After completion of the reaction, excess aniline was distilled off and the distillation residue was recrystallized from water. 12.7 g of phenylurea with a melting point of 145 DEG-148 DEG C. are obtained in this way. Examples 8 and 9 20 g, 0.3 mole of 90% ammonium isocyanate are suspended at room temperature or dissolved in 200 g of diluent and then the solution or suspension is reacted with a solution of 18.0 g, 0, 0 g. 15 mol of 1,6-diaminohexane in the same solvent and with stirring. The reaction mixture was then stirred at room temperature for 1 hour, then stirred for an additional 5 hours at 55-60 ° C and then cooled. The precipitate formed is filtered off with suction, recrystallized from water and then dried. Diluents as described below in Table 1 are used to carry out the reaction. Using water as diluent, 600 ml of water are added to the reaction mixture after completion of the reaction and the precipitate formed is then recrystallized directly from the reaction mixture. The yields of 1,6-hexanediurea having a melting point of from 20 to 205 ° C are also shown in Table 1 for each diluent used.

However, benzylurea can be obtained in the same manner as above, but using 32.2 g, 0.3 mol of benzylamine instead of 1,6-diaminohexane in the yields also shown in Table 1.

Analysis calculated for C 64.0, H 6.7, N 64.0%, found C 64.0, H 6.7, N 18.7%.

Table 1 Diluent Yield in% of theoretical 1,6-hexane-benzylurea urea n-hexane 85 76 toluene 73 67 chlorobenzene 56 56 tetrahydrofuran 71 79 dimethoxyethane 72 - 1,4-dioxane 74 72 ethanol 20 - water 59 56 Example 10 18 1.6 g of diaminohexane (0 g, 0.15 mole) is used as a preform in 200 ml of water and the reaction mixture is heated with stirring a) at 50 ° C or b) at 100 ° C. 20.0 g (0.3 mol) of 90M ammonium isocyanate are dissolved in water and added dropwise to the reaction mixture while stirring.

After completion of the reaction, 600 ml of water are added to the reaction mixture and the precipitate formed is recrystallized, filtered off with suction and then dried. There was thus obtained 1,6-hexanediurea having a melting point of 202 DEG-205 DEG C. in the case of a) in a yield of 45% of the theoretical amount and in the case of b) in a yield of 47% of the theoretical amount. EXAMPLE 11 14.11 g (0.2 mole) of 85% ammonium isocyanate are slurried in 200 ml of n-hexane and 48.3 g of 0.2 mol of dioctylamine dissolved in 200 ml of n-hexane are added. After the addition was complete, the reaction mixture was stirred at room temperature for 1 hour and then heated to reflux for 2 hours. After cooling the reaction mixture, a small amount of urea precipitates which is filtered off. The filtrate was distilled at 100 ° C and 3 to 4 Pa to remove volatiles. 51.0 g of N, N-dioctylurea are obtained in this way as a yellowish oil in 90% of theory.

Analysis calculated: C 71.8, H 12.8, N 9.8%, found C 71.9, H 12.9, N 9.8%.

Represented by: JUDr. Zdeňka KOŘEadvokátka

Claims (8)

11 PATENT CLAIMS A process for producing an N-monosubstituted or N, N-di-substituted urea characterized in that an ammonium isocyanate is reacted in a diluent with a primary or secondary amine? 2. The process of claim 1 wherein the reaction is carried out in a diluent inert under the reaction conditions. Process according to claim 1 or 2, characterized in that the inert diluent is an aliphatic or aromatic hydrocarbon, a chlorinated aliphatic or aromatic hydrocarbon, an ether, an alcohol or water. 4. The process of claim 1 wherein the primary or secondary amine is used as a diluent. znacujici 5. The process of claim 1, wherein the ammonium isocyanate and the primary or secondary amine are used in an equivalent amount to be used as a diluent early. | with e- if the amine is not Γ3Γ30 ťλΣ3Τνavgn 6. A process according to claim 1, wherein the ammonium isocyanate in the inert diluent is used in an overlay and a primary or secondary amine is added to the room while stirring at -20 DEG C. to room temperature and the mixture is reacted, whereupon the temperature to terminate the reaction increases to the boiling point of the diluent used as a template by a reflux condenser. e l 6 IIX X 0θ ~ 31 ° Q '66093' I <2 7. The process of claim 1 wherein the primary or secondary amine is optionally used, optionally together with an inert solvent, and ammonium isocyanate 12 is added with stirring at -20 [deg.] C. to room temperature, and the mixture is reacted thereafter. the reaction temperature increases. 8. A process according to claim 1, wherein the N-monosubstituted or N, N-disubstituted urea obtained is isolated from the reaction mixture by conventional means. Represents: Λ '0