DD154100A5 - PROCESS FOR THE PREPARATION OF CARBAMINE ACID ESTERS DERIVATIVES BY O-ACYLATION - Google Patents

Abstract

The invention relates to a process for the preparation of Carbaminsaeurephenylester derivatives by O-acylation of phenol derivatives by means of a novel O-acylating agent containing as acylating agent 5 to 50 wt .-% of a saccharin compound and a preferably equivalent amount of a base and 10 to 80% solvent contains. For example, methyl-N- (3-hydroxyphenyl) carbamate in acetone in the presence of triaethylamine is reacted with N-phenyl-carbamoyl-benzoic acid sulfimide to obtain 3-methoxycarbonyl-aminophenyl-phenylcarbamate.

Description

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Process for the preparation of carbamic acid ester derivatives by O-acylation

Field of application of the invention:

The invention relates to a novel process for the preparation of substituted Carbatninsäurephenylester derivatives by O-acylation of the corresponding phenols.

The inventively produced Carbaminsaurephenylester correspond to the general formula I ₁ wherein

R is an alkyl group having 1 to 8 carbon atoms

is an aryl group, a cycloalkyl group having 5 or 6 carbon atoms or an aralkyl group having 7 to 16 carbon atoms and the alkyl mono- or polysubstituted derivatives of this group,

R is hydrogen, an alkyl or alkoxy group with

1 to 4 carbon atoms or an acylamino

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group "means

E is hydrogen, halogen, an alkyl or alkoxy group having 1 to 4 carbon atoms,

the alkyl and / or alkoxy groups denoted by R and E "can also be closed to the ring via a C-G bond.

Most of the compounds of general formula I are used in agriculture as pesticides,

Characteristic of the known technical solutions:

It is generally known that the compounds of general formula I usually by addition of isocyanates of the general formula III to phenol derivatives of the general formula II - (in the formulas II and III is the meaning

12 of R, R and E are the same as above).

A disadvantage of this process is that the ST _A rk roxischen and mucous membranes acting isocyanates present problems of health and safety, through which also the technological process is greatly complicated · A further disadvantage is the highly exothermic nature of the addition reaction, which - in particular in isocyanates with low boiling point - causes further technological problems or offers the possibility of undesirable side reactions · Transport and storage of some isocyanates require special measures and special packaging units, which causes additional costs. The possibility of obtaining isocyanates is limited on a global scale. · · -

The compounds of general formula I could in principle also by reacting the compounds of the general

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Formula II prepared with monosubstituted Carbanimsäurechioxiden; However, in contrast to their disubstituted analogues, the monosubstituted carbamic acid chlorides are unstable substances which decompose to isocyanates with elimination of hydrochloric acid. These decomposable compounds can also be formed by addition of hydrochloric acid to isocyanates, but this is not the case. We expect that they will be able to acylate nucleophilic agents, for example compounds of general formula II, without prior removal of hydrochloric acid. Furthermore, the constituents mentioned in connection with the isocyanates consist to an even greater extent of the monosubstituted carbamic acid chlorides.

A further possibility for the preparation of the compounds., Of the general formula I is the reaction of the compounds of the general formula II with phosgene and the subsequent acylation of the resulting chloroformate derivatives with amines of the general formula R-NEW · The disadvantage of this process is the necessity to work with the extremely toxic phosgene gas.

Discussion of the nature of the invention;

It has now been found that the CarbaminsäurephenylesterDerivate of general formula I can be obtained in novel manner in high purity and good yield, if the phenols of general formula II in the presence of a base with N-carbamoylsaccharin derivatives of general formula IV ₅ wherein the Meaning of R is the same as above, O-acylated

As the base, inorganic bases, preferably alkali metal hydroxides, carbonates, -hydrogencarbante, alkaline earth hydroxides, carbonates, bicarbonates, but also organic bases, such as tertiary amines, preferably triethylamine, can be used "The base is useful in on

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the acylating agent is used in at least the equimolar amount.

The reaction of the compound of general formula II with the. Compound of the general formula IV is preferably carried out in an organic solvent or in an aqueous organic solvent medium. "Suitable organic solvents are hydrocarbons, lower ketones or esters (acetone, methyl ethyl ketone, ethyl acetate), ither (dioxane, tetrahydrofuran), chlorinated hydrocarbons (chloroform, dichloroethane Preferred are solvents in which at least one of the starting materials and the base are soluble, but the resulting compound of general formula I is insoluble or in solution in a form such that other components are not precipitated during their precipitation * When using inorganic bases, the product is, if necessary , slurried in water for purification. Taking into account the fact that the salt-like adducts formed from organic bases dissolve in organic solvents It is more advantageous to use organic bases, especially in systems in which the resulting compound of general formula I is insoluble, while the organic base and the adduct of saccharin are soluble.

The implementation of the compounds of. general formulas II and IV can be carried out at temperatures between 0 and 100 ^° C. The reaction is preferably carried out at room temperature. The resulting target products are preferably separated off by crystallization or precipitation with a suitable solvent, while the saccharin split off in the reaction is in the form of its The salt formed in the base remains in solution and, if desired, simply removed.

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separates and can be used again for the preparation of the acylating agent of general formula IV.

The novelty of the method is that the compounds of general formula I were previously produced only by addition reactions or by two-step substitution reactions, but according to the invention, the compounds of the general formula I is prepared in one step by a substitution reaction. This makes it possible to produce the compounds in an aqueous medium.

The process according to the invention is advantageous since, in contrast to the known processes, no toxic liquid or solid acylating agents are used. The N-carbamoyl saccharin derivatives are solid, crystalline compounds, easy to store and handle. The Äcylierungsreaktion made with them is much less exothermic than, for example, the reaction of the isocyanates. As a result, no harmful side reactions occur, and the compounds of the general formula I can be obtained in good yield and in high purity.

An acylating agent suitable for the acylation of phenolic hydroxyl groups contains as acylating agent 5 to 50% by weight of a compound of general formula IV, wherein the meaning of R is the same as above, further from 0.2 to 30% by weight, but on the acylating Agent at least the equimolar amount of a base and 10 to 80 Gev \ ',% .-% solvent.

A preferred embodiment of the acylating agent contains as the acylating agent N-phenylcarbamoyl-benzoic acid sulfimide, N-methyl-carbamoyl-benzoic acid sulfimide or N- (methylpheny1) -carbamoyl-benzoic acid

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sulfimide and as the base triethylamine, while acetone is preferred as the solvent

AusführunKsbeispiele:

The invention will be explained in more detail below with reference to examples.

example 1

4.3 S (0 * 025 mol) of methyl N "(3-hydroxyphenyl) carbamate are dissolved in 15 ml of acetone in the presence of 2.56 g (0.025 mol) of diethylamine with 7" 3 g (0.025 mol) of N-phenyl carbamoyl-benzoic acid sulfimide (m.p .: 184-186 ⁰ C) was reacted for 15 minutes at 40 ⁰ O "Das'Reaktionsgemisch is mixed with 40 ml of water and cooled to 5 10 ⁰ C his" After half an hour the product is filtered, washed and dried "5> 5 g of 3-methoxycarbonyl ~ aminophenyl-phenylarba" mat is obtained which melts at I50 to 152 ⁰ C. The Benzoesäuresulfimid can be precipitated from the mother liquor with hydrochloric acid

Example 2

3.35 g (0.025 mol) of 2,3-dihydro-2,2-dimethylbenzofuran-7-0I are dissolved in 15 ml of acetone in the presence of 2.56 g (0.025 mol) of triethylamine with 6 g (0.025 mol) of N -Methylc _a rbamoylbenzoesäure sulfimide at 50 ⁰ C for 15 minutes reacted · The reaction mixture is diluted with 100 ml of water and cooled to room temperature, the precipitated product is filtered off, washed with water and then dried x 3 »1 g of 2,3-dihydro- 2,2-Dimethylbenzofiiran-7 ~ ylmethylcarbamat be obtained, which melts at 150 to I52 C. The benzoic acid sulfimide can be regenerated from the mother liquor by acid precipitation.

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Example 3

1 »5 SN-methylcarbamoyl-benzoesäuresulfimid are suspended in a mixture of 1 g of 2,3-Eihydro ~ 2,2-dimethylbanzofuran-7-ol, 5 hüL of acetone and 5 ml of water, at room temperature with stirring within 20 minutes 0.6 g of triethylamine, dissolved in a mixture of 2 ml of acetone and 1 ml of water, added dropwise. Then 20 ml of water are added dropwise to the reaction mixture within 30 minutes. After stirring for 1 1/2 hours, the crystals are filtered off, with water washed and then getrock- net ¹ "0.745 g 2J3 - dihydro-2 _s 2 ~ dimethyl-benzofuran-7 ~ yl - methylcarbamate are obtained, which melts at I50 to 152 ⁰ C."

Example 4

4 "3 S (0.025 mol) of methyl N- (3-hydroxyphenyl) carbamate are imid in 15 ml of acetone in the presence of 2 g (0.014-5 mol) of potassium carbonate with 7j3 g (0.025 mol) of N-phenylcarbamoyl-benzoic acid sulfide (Mp: 184 to 186 ⁰ C) refluxed for 15 minutes * The reaction mixture is mixed with 40 ml of V / asser and cooled to 5 to 10 ⁰ C »After one hour, the precipitate is filtered off and washed dried 5s8 g • 3 -MethoxyGarbonylaminophenylcarbamat are obtained, which melts at 150 to 152 ⁰ C ·

Example.,%

4} 5 S (Ο »Mol25 mol) of ethyl N- (3-hydroxyphenyl) carbamate in 15 ml of acetone in the presence of 2.56 g (0.025 mol) of triethylamine with 7> 3 g (0.025 mol) of N-phenylcarbamoyl -benzoesäuresulfimid reacted for 15 minutes at 40 ⁰ C »Nach.Zusatz of 40 ml water the mixture is cooled to 5 ° 0 After 30 minutes of standing off the product is filtered, washed and dried" 5 | 7 g of 3-phenylcarbamate A'thoxycarbonylaminophenyl v / earth, which melts at II7 to 119 ⁰ Cβ

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Example 6

4.3 S (0 * 025 mol) of methyl N- (3-hydroxyphenyl) carbamate are dissolved in 15 ml of acetone and in the presence of 2.56 g (0.025 mol) of (Driäthylamin with 7.9 g (0.025 mol) of N - (3-Methylpheiiyl) ⁰ C reacted carbamoyl-benzoic acid sulf imide at 3O 30 minutes After addition of 50 ml water, the mixture is cooled to 5 to 1O ⁰ O After 30 minutes of standing off the product is filtered, washed and.. dried »5.3 g of 3-Methoxycarhamoylphenyl ^ '- methylphenylcarbamate be obtained which melts at 140 to 142 ⁰ C _o from the mother liquor can be regenerated by precipitation with hydrochloric acid 3> 5 S (76 ^) Benzoesäuresulfimid · This is in all of above examples possible

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Example 7

5 g of N-methylcarbamoyl-benzoic acid sulfimide are suspended in a mixture of 2.67 g of 2-chlorophenol and 50 ml of acetone, the suspension is cooled to 5 ⁰ C and then dropwise with constant stirring, the solution of 2.9 ml of triethylamine in Added 30 ml of acetone. During the addition (2 hours), the temperature of the mixture does not rise above 6 ° C. The reaction mixture is stirred at this temperature for 12 hours and then treated with 240 ml of distilled water. Then the mixture is extracted three times with 30 ml of ether. The combined ethereal extracts are dried over anhydrous sodium sulfate and then evaporated in vacuo at not more than 30 ° C. 3.13 g of N-methylcarbamic acid - (2-chlorophenyl) ester are obtained, which melts after recrystallization from n-pentane at 90 to 91 ⁰ C.

Example 8

5 g of N-methylcarbamoyl-benzoic acid-sulfimide are suspended in a mixture of 2.6 g of 2-methoxyphenyl and 50 ml of acetone. With constant stirring, the solution of 2.9 ml of triethylamine in 30 ml of acetone is added dropwise at room temperature within one hour. The reaction mixture is stirred for a further 2 hours at room temperature and then treated with 240 ml of distilled water. The mixture is extracted three times with 30 ml of ether. The combined ethereal extracts are dried over anhydrous sodium sulfate and then evaporated in vacuo at not more than 30 ⁰ C. 2.43 g of N-methylcarbamic acid (2-methoxyphenyl) ester are obtained, which melts after recrystallization from n-pentane at 90 to 92 ⁰ C.

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Example 9

2.4 g of N-methylcarbamoyl-benzoic acid sulfirnide are suspended in a mixture of 1.63 g of 2-methoxy-4-cyanomethylene-phenol and 15 ml of acetone. With constant stirring, the solution of 1.4 ml of triethylamine in 5 ml of acetone is added dropwise to the suspension at room temperature within one hour. The mixture is stirred at room temperature for a further 2 hours and then treated with 65 ml of distilled water. The mixture is stirred at 5 ⁰ C for 16 hours allowed to stand, then the precipitated N-Methylcarbaminsäure- (2-methoxy-4-cyanomethylene-phenyl) ester is filtered off and washed with 5 ° C warm water. 0.72 g of product is obtained which melts at 138 to 139 ° C.

Elemental analysis: Pty * * / Q - 59 99 H % = 5 45 N % = 12 72 found: β 60 , 05 H % = 5 , 52 N % = 12 65

The mother liquor is washed three times with 10 ml of ether, the combined ethereal extracts are dried over anhydrous sodium sulfate and concentrated in vacuo, at most 30 ° C. In this way, further /, 95 g of product are obtained.

Example 10

5 g of N-butylcarbamic acid-benzoic acid sulfimide are suspended in a mixture of 1.67 g of phenol and 50 ml of distilled water. To the suspension at room temperature with constant stirring within 5 hours 0.71 g of sodium hydroxide in 50 ml of distilled water was added dropwise. The reaction mixture is stirred for a further three hours, then extracted three times with 30 ml of ether, and the combined ethereal extracts are dried over anhydrous sodium sulfate.

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dried and then evaporated in vacuo at not more than 30 ⁰ C. 2.15 g of N-Butylcarbaminsäurephenylester are obtained. Boiling point: 146 to 143 ° C / 2 Torr.

Example 11

5 g of N-tert-butylcarbamoyl-benzoic acid sulfimide and 1.9 g of 4-MQthylphenol be heated in 50 ml of chloroform to the boiling point. Then 2.5 ml of triethylamine in 30 ml of chloroform are added dropwise with constant stirring within one hour. The mixture is boiled for one hour and then evaporated in vacuo. The oily residue is stirred with 100 ml of ether. The precipitated benzoic acid sulfimide triethylamine salt is filtered off and the filtrate is evaporated in vacuo at not more than 30 ° C. 2.4 g of N-tert-Butylcarbaminsäure- (4-methylphenyl) ~ ester behavior, which melts after recrystallization from petroleum ether at 131 to 132 ⁰ C.

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To this 1 page Formein

-0-C-NH-R

(I)

-OH OD. R-N = C = O CU)

0 N-C-NH-R

SO ₂

KK)

Claims (6)

- 12 - 2 2 4 9 8 Invention claim: 1 2 R and R are the same as above , in the presence of a base with N-carbamoyl saccharin derivatives of the general formula IV in which the meaning of R is the same as above. 1. A process for the preparation of Carbaminsäurephenylester-Oerivaten of the general formula I, wherein R represents an alkyl group with 1 to 8 carbon atoms, an aryl group, a cycloalkyl group with 5 or 6 carbon atoms or an aralkyl group with 7 to 16 carbon atoms and represents the alkyl-mono- or polysubstituted derivatives of these groups, R is hydrogen, an alkyl or alkoxy group having 1 to 4 carbon atoms or a Acylamino group means R is hydrogen, halogen, .. an alkyl odor Alkoxy group having 1 to 4 carbon atoms stands, with the S
R and R ™ denote alkyl and / or alkoxy groups via a C-C bond may also be closed to the ring, by C-acylation of phenol derivatives of the general formula II, in which 2 R and R are as defined above, characterized in that the Phenolderiwate the general formula II, wherein the meaning of 2. The method according to item 1, characterized in that one carries out the acylation in the presence of at least equivalent amount of base. - 13 - 22 A 9 88 3. The method according to item 2, characterized in that one uses inorganic bases, preferably alkali metal hydroxides, carbonates, bicarbonates, alkaline earth metal hydroxides, carbonates, bicarbonates, or tertiary amine bases, preferably triethylamine. 4. The method according to any one of items 1 to 3, characterized in that reacting the compounds of general formulas II and IV in an organic solvent or in an aqueous organic solvent medium or in water with each other. 5. The method nech one of the items 1 to 4, characterized by reacting the compounds of the general formulas II and IV at temperatures between 0 and 1OO ° C, preferably at room temperature, together. 6 "process according to one of the items 1 to 5, characterized in that as phenol derivative 2,3-dihydro-2,2-dimethylbenzof uran-.7-ol, alkyl N- (3-hydroxyphenyl) carbamates or 2- (l, 3-dioxolan-2-yl) phenol used.