DE2529549C3 - Process for the preparation of phenylisopropylureas - Google Patents

Description

CH ₁

C-X

(Π)

in which X stands for a chlorine or bromine atom, with urea or a urea derivative of the general Formula:

H ₁ NCONHR

(Ul)

in which R has the meaning given.

2. The method according to claim 1, characterized in that the reaction is carried out in the presence of oc-methylstyrene carries out.

3. The method according to claim 2, characterized in that the reaction is carried out in the presence of 1 to 10 moles of Λ-methylstyrene, based on 1 mole of cumyl halide, carries out.

4. The method according to claim 3, characterized in that the reaction is carried out in the presence of 3 to 6 moles of Λ-methylstyrene, based on 1 mole of cumyl halide, carries out.

5. The method according to claim 1, characterized in that the reaction is carried out at a temperature of 0 to 10O ⁰ C.

6. The method according to claim 5, characterized in that the reaction is carried out at a Temperature of 10 to 80 ° C carries out.

7. The method according to claim 1, characterized in that the reaction with urea in carried out in an aqueous medium.

8. The method according to claim 1, characterized in that the reaction with urea in carries out an aqueous medium in the presence of Λ-methylstyrene.

9. The method according to claim 1, characterized in that the reaction with urea derivatives of the general formula HI, in which R stands for an optionally substituted phenyl radical, is carried out in a strongly polar aprotic solvent.

10. The method according to claim 1, characterized in that the reaction with urea derivatives of the general formula III, in which R is an optionally substituted phenyl radical or a

Phenylalkyl, in a strongly polar aprotic solvent in the presence of Ä-Methylstyrene carries out.

The invention relates to a process for the preparation of phenylisopropylureas, d. H. N- (a, * - dimethylbenzyl) -N'-substituted or unsubstituted ureas, of the general formula

CH ₃

C- NHCONHR

CH ₃

in which R represents a hydrogen atom, one which is optionally substituted by at least one Ct-alkyl radical Phenyl radical or a phenylalkyl radical.

These phenylisopropylureas are suitable as herbicides, as starting materials for the production of Intermediates. For example, compounds of the general formula I in which R stands for. a optionally substituted phenyl radical, can be used in a highly effective manner as herbicides. the Compound of the general formula I in which R represents a hydrogen atom can easily be reacted convert with sodium nitrite in the presence of hydrogen chloride into the corresponding cumyl isocyanate. The The isocyanate formed in the process is an intermediate product for a wide variety of organic compounds. For example, if this isocyanate is reacted with N-Methylani-Hn, it is obtained as a herbicide useful N - («, Ä-Dimethylbenzyl) -N'-phenylurea.

As a rule, urea derivatives are obtained by reacting primary or secondary amines with Isocyanates. The starting isocyanates are usually by reacting the corresponding amines with an excess of phosgene produced. However, the use of phosgene requires an accurate one Control to avoid environmental pollution or pollution. Especially among the It is often difficult to deal with currently strict environmental protection requirements in industrial plants Phosgene to work.

According to a very special manufacturing process for urea derivatives, ureas and olefins are made or alcohols are used as starting materials. However, such a method is not suitable for Production of phenylisopropylurea derivatives of the general formula I. Tests have shown that that the relevant compounds of general formula I are hardly after such a process can be produced.

In contrast to this, according to the invention, a highly advantageous process for the production of Phenylisopropylureas of the general formula I developed without the need for humans and animal highly dangerous phosgene and without compulsion to use a special pressure reactor at relatively low reaction temperature and normal (atmospheric) pressure high yields of the desired Phenylisopropylureas supplies.

I.

The invention now relates to a process for the preparation of phenylisopropylurea derivatives general formula

CH,

- C-NHCONHR

(D

in which R is a hydrogen atom, optionally substituted by at least one Ci-G, -alkyl radical Phenyl radical or a phenylalkyl radical, which is characterized in that one is a cumyl halide the general formula

-CX CH ₃

(Π)

in which X stands for a chlorine or bromine atom, with urea or a urea derivative of the general formula

H ₂ NCONHR

(Hl)

in which R has the meaning given.

From Peter A. S. S m i th in "The Chemistry of Open Chain Organic Nitrogen Compounds", Volume 1, page 271, W. A. Benjamin, Inc., New York, 1965, it is known that alkylating agents take ureas under Attack formation of isourea salts on the oxygen atom. This means that when there is a reaction no dehydrohalogenation occurs between an organic halide and urea. So became for example benzyl chloride with urea under the mild conditions maintained according to the invention implemented, whereby it could be ensured that hardly any dehydrochlorination took place. With regard to it is completely unexpected and surprising that the reaction of a cumyl halide general formula II with urea or a urea derivative of the general formula IH im Within the scope of the process according to the invention with dehydrohalogenation taking place without further ado Phenylisopropylureas of the general formula I form.

Specific examples of ureas of the general formula I which can be prepared according to the invention are N-aA-dimethylbenzyl) urea, N - {<% A-dimethylbenzyl) -N'-phenylurea, N - («A-dimethylbenzyl) -

N '- (o-, m- or p-) - tolylurea, N- (oA-dimethylben2yl) -

N '- (2,4-dimethylphenyl) urea, N- (aA-dimethylbenzyl) -N'-benzylurea, N - («A-dimethylbenzyl) -N '- (α-methylbenzyl) urea and

N, N'-bis (iXA-dimethylbenzyl) urea. The structural formula given shows that the urea derivatives according to the invention by a quaternary carbon atom of the phenylisopropyl radical (α, α-dimethylbenzyl radical) on the nitrogen atom to which a hydrogen atom is still attached. Furthermore, there is at least one hydrogen atom on the other nitrogen atom of the urea skeleton bound.

Leave the cumyl halides used as starting materials in the process according to the invention easily by converting what is inexpensively available in the petrochemical industry Obtain α-methylstyrene with a hydrogen halide. From the connections of the general form! Urea is commercially available. The substituted ones Urea compounds can be obtained by reacting the corresponding amines, e.g. B. of aniline or toluidine, with sodium cyanate in aqueous hydrochloric acid solution. Needless to say, it goes without saying that the starting materials which can be used according to the invention do not affect those according to the manufacturing processes described manufacturable starting materials are limited.

Since the cumyl halides of the general formula II are relatively unstable compounds, is it is advisable to prepare them immediately before they are implemented. You can also do it while performing of the method according to the invention can be produced in situ. For example, methyl styrene is left with a hydrogen halide to form a cumyl halide of the general formula II react, whereupon the urea compound of the general formula III is added. On the other hand, a Hydrogen halide in a mixture of -methylstyrene and the urea compound of the general formula III are introduced with stirring. The cumyl halide formed is then in situ with the urea compound implemented.

The process according to the invention can be carried out in the absence of a solvent. Preferably however, it is carried out in the presence of a solvent. To this end are for example aprotic solvents are suitable. If the starting material of the general formula HI Is urea, hydrocarbons can also be used. Water can also be used as a solvent whichever is preferred. If the starting material of the general formula Hl one Contains phenyl radical or an alkyl-substituted phenyl radical, should appropriately aprotic Strong polarity solvents are used. For example, dimethylformamide, acetonitrile, Dimethylsutfoxid, nitromethane, nitrobenzene, methyl isobutyl ketone, Methyläthylketoii and / or acetone. Mixtures of these solvents with small amounts of other aprotic solvents, such as dioxane, tetrahydrofuran, cyclohexanone, chloroform, chlorobenzene, benzene, toluene, xylene or ether, be used. There are no specific limits on the amount of solvent to be used; h., the The amount can be selected depending on how the method according to the invention is carried out.

It has been shown that particularly good results are obtained when the described reaction is carried out in the presence of oc-methylstyrene. In such a case, the -methylstyrene presumably captures the hydrogen halide formed as a by-product and converts into the cumyl halide of the general formula II, which then again takes part in the reaction with the urea compound of the general formula III. The -methylstyrene can be added to the reaction mixture during the course of the reaction or it can be present from the start as an excess (based on the -mei'nylstyrene required with the hydrogen halide in the preparation of the starting cumyl halide). The amount of α-methylstyrene per mole of cumyl halide is expediently 1 to moles, preferably 3 to 6 moles.
The method according to the invention is almost running

stoichiometric. To suppress side reactions or to improve profitability and productivity, however, the reaction should preferably be carried out in such a way that one or the other of the starting materials is present in a slight excess. Preferably the urea compound of the general formula SH used in excess, d. H. in an amount greater than 1 mole up to about 5 Moles per mole of cumyl halide of the general formula 11. When used as a urea compound of the general Formula III urea itself is used and the reaction proceeds in the presence of water should the The amount of urea is expediently at least 2 mol. The reason for this is that the urea as Catches by-product formed hydrogen halide and converts into a hydrogen halide salt. This here formed salt no longer takes part in the implementation.

The process according to the invention takes place under relatively mild conditions. The reaction temperature is generally from 0 to 100 ⁰ C, preferably 10 to 8O ⁰ C. Concerning the reaction pressure, there are no specific rules; The reaction is usually carried out at atmospheric pressure. In any case, the temperature and pressure conditions can be varied as desired within reasonable limits. However, if the temperature is too high, undesired decomposition with polymerization of the starting materials or the end product occurs, or other side reactions can occur. Consequently, as a rule, heating to a temperature above 100 ^° C. should be avoided. The reaction time is usually inversely related to the reaction temperature. At higher temperatures it is one to several hours, at lower temperatures 1 to 4 day (s).

All reaction products of the general formula I are solid at room temperature and can from the Reaction products are obtained in crystalline form. The crystalline products can, if desired be purified in the usual way, for example by recrystallization.

The following examples are intended to illustrate the process according to the invention in more detail. Not so far otherwise stated, all statements mean “parts” - “parts by weight”.

example 1

A mixture of 154.5 parts of cumyl chloride and 120 parts of urea was ^{reacted at a temperature of 70 °} C. for 3 h with stirring. The reaction mixture obtained was cooled with ice, and 1000 parts of a 2N aqueous sodium hydroxide solution were added dropwise with stirring, whereby colorless crystals were deposited. The obtained crystals were separated from the mother liquor, washed with water and n-hexane, and finally dried, whereby a total of 139 parts of colorless crystals were obtained. The crystals obtained contained, by nuclear magnetic resonance spectral analysis, [<5 = 1.73 (6 H, s); δ = 5.91 (2H, broad s); ό = 6.93 (1H, broad s); ό = 7.1-7.7 (5 H, m), 35 ° C, 60 MC, d6-pyridine solvent, 5% by weight solution, TMS reference] N- (a, (X-dimethylbenzyl) urea ( Compound of the formula III: R = H) with a purity of 89%. The remainder (11%) consisted of N, N'-bis (aA-dimethylbenzyl) urea (compound of the formula IH: R = -C (CHs) JQHs ) [Nuclear magnetic resonance spectrum ·, ό = 1.67 (12 H, s), ό = 6.42 (2 H, broad s), δ = 7.1-7.7 (10 H, m) corresponding conditions as already given ].

The two compounds were separated from one another by fractional crystallization from aqueous alcohol separated. The first compound had a melting point of 190.5 to 191 ° C, the last compound a melting point of 226 to 227 ° C.

Example 2

180 g (3 mol) of urea were dissolved in 100 ml of water. The solution obtained was heated to a temperature of 55 ^° C. and 155 g (1 mol) of cumyl chloride were added dropwise with stirring over the course of 2 hours. After completion of the addition, the reaction was continued for a further 3 hours at a temperature of 6O ⁰ C. After cooling, the reaction product obtained was neutralized with 2η aqueous sodium hydroxide solution. The deposited crystals were filtered, washed with a small amount of n-hexane and then washed with water and finally dried in vacuum at a temperature of 8O ⁰ C, and 151 g of colorless crystals were obtained. These were identified as N- (a, a-dimethylbenzyl) urea with a purity of 94%. The remainder (4%) consisted of N, N'-bis («, a-dimethylbenzyl) urea.

Example 3

A mixture of 15.4 g (100 mol) of cumyl chloride, 18.0 g (300 mol) of urea and 30.0 g of α-methylstyrene were stirred at a temperature of 60 ° C for 5 hours. The crystals thereby deposited were filtered off, neutralized with a 1 η aqueous sodium hydroxide solution, washed with water and finally dried, 17.5 g of colorless crystals being obtained became. These consisted of N - (<xA-dimethylbenzyl) urea a purity of 98% and contained 2% N, N '- bis («A-dimethy lbenzyl) urea f.

Example 4

102 parts of phenylurea were suspended in 80 parts of acetonitrile, and 25.4 parts of an α-methylstyrene solution containing 30.5% cumyl chloride were added. The reaction mixture was allowed to react at a temperature of 40 ^° C. for 5 hours while stirring. After the reaction product had been left to stand for 2 days, the crystals which separated out were separated off from the mother liquor and recrystallized from hydrous alcohol, 7.6 parts of N-phenyl-N '- (tXA-dimethylbenzyl) urea (compound of the formula IH: R = C ₆ H ₅ ). The melting point of the crystalline compound was 193 to 194 ° C.

Example 5

11.3 parts of p-tolylurea were suspended in 80 parts of acetonitrile and treated with 7.7 parts of cumyl chloride and 24 parts of "methylstyrene With stirring, the reaction mixture wvirde 6 hours at a temperature of 40 ⁰ C then reacted the reaction mixture was allowed to stand for 2 days. The crystals which precipitated out were separated from the mother liquor, washed with n-hexane and recrystallized from 60% methanol, 13.8 parts of N - («A-dimethylbenzyl) -N '- (p-tolyl) urea (compound of the formula III: R = C6H.4-CH.3-p) were obtained with a melting point of 203 ⁰ C.

Example 6

11.3 parts of p-tolylurea were in 50 parts Nitrobenzene suspended and with 30 parts of a-methylsty-

rol shifted. The resulting mixture was stirred while portionwise anhydrous hydrobromic acid was added. After the amount of the mixture increased by 10 parts, it became Introducing the hydrobromic acid stopped. Then the reaction was carried out at one temperature for 5 hours allowed to drain from 40 ° C. The reaction mixture was finally left to stand overnight. To 30 parts of η-hexane were added and the reaction mixture was left to stand again overnight. The one here Crystals which separated out were recrystallized from 50% strength methanol, 13.4 parts of N - («A-dimethylbenzyl) -N '- (p-tolyl) urea with a melting point of 203 ° C were obtained.

Example 7

12.4 parts of 2,4-xylylurea were suspended in 50 parts of acetonitrile, and 7.7 parts of cumyl chloride and 24 parts of methylstyrene were added. While stirring, the reaction mixture was for 6 hours at a temperature of 4O ⁰ C allowed to react. After the reaction mixture was left to stand for one day, 50 parts of η-hexane were added. Then the reaction mixture was left to stand overnight. The crystals which precipitated out were separated from the mother liquor and recrystallized from 60% methanol, 12.5 parts of N- (a, a-dimethylbenzyl) -N '- (2,4-xylyl) urea' (compound of the formula III: R = -C ₆ H ₃ (CH ₃ ^ -2.4) with a melting point of 163 ° C.

Example 8

Anhydrous hydrochloric acid was introduced into 30 ml of α-methylstyrene, which was located in a 200 ml reactor, with external cooling with ice at a temperature of 0 to 10 ° C. When the weight of the mixture increased by 1.8 g, the introduction of the hydrochloric acid was stopped. 11.3 g of p-tolylurea and 40 parts of acetonitrile were then added with stirring, and the reaction mixture was heated. After 4 hours heating at a temperature of 40 ° ± 2 ° C, the reaction mixture was allowed to stand for 3 days at a temperature of 2O ⁰ C. The crystals which precipitated out were separated from the mother liquor and recrystallized from 70% methanol, 13.5 g of N- (α, ot-dimethylbenzyl) -N '- (p-tolyl) urea having a melting point of 203 ° C. being obtained .
5

Example 9

The mother liquor from Example 8, separated from the precipitated crystals, was mixed with 16 ml of a-methylstyrene, 2 ml cumyl chloride and 11.3 g p-tolyl urea offset. The reaction mixture was then reacted for 4 hours at a temperature of 40 ° C. and then 3 Left for days. The crystals thereby precipitated were separated and made from 70% methanol recrystallized, with another 12.8 N- (a, a-dimethylbenzyl) -N '- (p-tolyl) urea were obtained.

Example 10

11.25 parts of p-tolylurea, 7.72 parts cumyl chloride and 23.64 g oc-MethylstyroI were added methyl isobutyl ketone in 80 parts, whereupon the reaction mixture for 5 hours at a temperature of 6O ⁰ C was allowed to react. After the completion of the reaction, the solvent was evaporated under reduced pressure. The evaporation residue was washed with n-hexane and recrystallized from a water / methanol mixture, 5.4 parts of N- (α, «- dimethylbenzyl) -N '- (p-tolyl) urea being obtained.

Example 11

Example 7 was repeated, but using the same amount of tetrahydrofuran instead of methyl isobutyl ketone has been used. 3.4 parts of N - («A-dimethylbenzyl) -N '- (p-tolyl) urea were obtained receive.

Example 12

7.7 parts of cumyl chloride and 13.4 parts of cumylurea were in a mixture of 20 parts of acetonitrile and 5 Parts of tetrahydrofuran entered, whereupon the reaction mixture is stirred for 1 hour at a temperature of 50 ° C was heated. Then the reaction mixture was concentrated under reduced pressure and the resulting residue was recrystallized from 60% methanol, with 8.8 parts N, N-bis («, oc-dimethylbenzyl) urea with a melting point of 226 to 227 ° C were obtained.

Claims (1)

Patent claims: t. Process for the preparation of phenylisopropylureas of the general formula: C-NHCONHR (D in which R is a hydrogen atom, optionally substituted by at least one C 1 -C 4 -alkyl radical Phenyl radical or a phenylalkyl radical, characterized in that one Cumyl halide of the general formula: