FI61873C - FOER FARING FOR FRAMSTAELLNING AV N- (CARBAMOYLOXYFENYL) CARBAMATE - Google Patents

Description

Εϋ ^ Ι [Β] (11) ANNOUNCEMENT η l j '' utlAggningsskrift o I O t ό 2¾¾ c ^ stc-NUi nyinr. tty tl 10 '002 (51) Kv.ik? / intci? C 07 c 125/075 ENGLISH - EN N LAN D (21) IWtdhskumus —f ^ ittnsöknlng 752008 (22) HsksmlsptWt - Ansttknlngsdsg 10.07.75 (23) Alkupllvt - Glltlghutsdsg 10.07 * 75 (41) Tullut Julkltaksl - Bllvlt j6

Patent and Registration Office "" , . ,, ..,,. Q_ -,,,. . , (441 Date of Nihtivllulpanon {a moonlight - 30.06.82

Patent and registration authorities Ansakin utlagd och utl.skrtftan publkarad (32) (33) (31) Requested privilege —Bagird prlorltet 12.07.7 * +

Hungary-Hungary (HU) CI-1U9O

(71) Chinoin Pharmaceuticals and Chemicals Gyira R.T., To. U. 1-5>

Budapest IV, Hungary-Hungary (HU) (72) Geza Toth, Budapest, Gabor Szabo, Budapest, Tamäs Kdllay, Budapest,

This invention relates to the preparation of N- (carbamoyloxyphenyl) carbamate. preparation of (carbamoyloxyphenyl) carbamates.

The present invention relates to a process for the preparation of N- (carbamoyloxyphenyl) carbamates of the formula 10 / r-O-C-N 2 -rh 3 -NH-C-OR

wherein R 1 is C 1 -C 4 alkyl, C 1 -C 4 cycloalkyl or an optionally halogen or C 1 -C 6 alkyl substituted phenyl group, R 1 is hydrogen or C 1 -C 7 alkyl, R 1 is C 1 -C 4 alkyl; alkyl. The process according to the invention is characterized in that the carbamate of the formula III

2 61873

OH

3-f-NH-C-OR · 3 (III) ^ 5. 3

wherein R is as defined above, is reacted with an ester of formula II in the presence of triethylamine

Cl Cl 0 ^ R1 J- \ Il (TI)

Cl-V ^ _ 7 “0-C-N <^

Cl Cl \ r2. 1 o wherein R and R have the same meaning as above.

The C 1 -C 7 alkyl may be a straight-chain or branched alkyl group, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, etc. The C 1 -C 4 cycloalkyl group is e.g. cyclopropyl, pentyl, hexyl, etc. The phenyl optionally substituted by halogen or substituted by C 1 -C 4 alkyl may be a phenyl, monochlorophenyl, monobromophenyl or methylphenyl group, preferably an m-tolyl or phenyl group.

The process according to the present invention is particularly suitable for the preparation of the following compounds of formula I: methyl N-3- (3'-methylphenyl) carbamoyl / phenylcarbamate, ethyl N-3- (N1- (phenyl) carbamoyl) -fenyylikarbamaatti.

The carbamates of formula I can be prepared by a variety of methods. In known methods, it is a general feature to acylate the acidic hydroxyl group of the corresponding N-hydroxyphenyl carbamate using reactive carbonic acid derivatives.

When isocyanates are used, the compounds of formula I can be prepared in a 1-step addition reaction in the presence of a basic catalyst. Org. Chem. 28, 658 (1963), Helv. Chim. Acta 48, 2005 (1965), Hungarian Patent No. 154.0477 *

The final products of formula I can also be prepared in a substitution reaction - by phosgenation - in two steps, first forming the corresponding chloroformate, which is reacted with the corresponding amine, or the carbamic acid chloride previously formed from the amine is reacted with the corresponding N-hydroxyphenyl carbamate. Org. Chem. 8, 101 (1952), Chem. Pharm. Bull. 15, 2015 (1967), Hungarian Patent Nos. 154,047 and 157,0447 · 3,61873

The compounds of formula I can also be prepared by a substitution reaction without prior preparation of chloroformate or carbamic acid chloride by simultaneously carrying out a reaction between phosgene, the corresponding N-hydroxyphenylcarbamate and the corresponding amine (Hungarian Patent No. 154,044).

The use of so-called active carbamic acid esters as acylating agents is known from peptide chemistry - French Patent No. 872,920, Nature 175, 685 (1955).

It is further known that highly reactive carbamic acid phenyl esters can be used for N-acylation (Hungarian Patent No. 162,382).

In the process of the present invention, active N-arylcarbamic acid esters are used for the O-acylation of a phenol derivative in which the substituents are primarily substituted groups.

Examining the acylation reactions of N-hydroxyphenyl carbamates, it has been found that the compounds of the formula I can be prepared by a new process in very pure form using active carbamic acid phenyl esters. This method is more advantageous from both a quantitative and a qualitative point of view than the acylation carried out using phosgene, isocyanates or active N-alkylcarbamoyl esters. Thus, when the O-carbamoylation of N-hydroxyphenyl carbamates according to known methods was carried out by an addition reaction (isocyanate) or by a 2-step substitution reaction (phosgene), the present invention provides a 1-step substitution reaction for carrying out O-carbamoylation.

The reaction can be preferably carried out in an organic solvent. It is preferred to use an organic solvent in which two of the starting materials (including triethylamine) are soluble and the resulting compound is either insoluble or can be isolated in pure form by precipitation or fractional crystallization while leaving the impurities in solution. Aromatic hydrocarbons (e.g. toluene), lower ketones (e.g. acetone), esters (e.g. ethyl acetate), ethers (e.g. dioxane), chlorinated hydrocarbons (e.g. chloroform) can be preferably used.

The carbamylating agents of the formula II can be prepared by known methods used for the preparation of phenyl or thiophenyl esters. Org. Chem. 28, 658 (1963) _7 \

The salt of the phenol component of the active ester formed in the reaction can be easily separated from the reaction mixture and returned to the process 4,61873, whereby it can be used to prepare the active ester, e.g., as follows:

The mother liquor is mixed with a 10% excess (compared to the phenol component) of 10% sodium hydroxide solution. After separation of the phase, the aqueous phase is acidified to pH 1 by adding 1: 1 dilute hydrochloric acid, the precipitated phenol is filtered off, washed and dried. Recovery rate 90%.

The tertiary amine can be recovered as the hydrochloride salt by evaporation or basification and distillation. In addition to the purity and high yield of the product, the advantages of the method are a simple recovery method and economy.

The compounds of the formula I prepared according to the process of the present invention can be converted into herbicidal mixtures by methods known per se. A powder mixture or a stabilized emulsion is prepared from the active substance. Emulsions may be prepared by mixing the active ingredient with a suitable solvent, optionally with one or more emulsifying agents. The amount of additives and solvent, the type and nature of the additive and carrier, and the percentage of active ingredient are selected taking into account the conditions of use. The active ingredient content of the preparation can vary within wide limits and is generally from about 0.001% to about 95%.

Further details of the present invention can be found in the following examples.

Example 1 To 50 ml of chloroform are added 8.0 g (0.02 moles) of pentachlorophenyl N- (n-tolyl) carbamate and 3.34 g (0.02 moles) of methyl N- (3-hydroxyphenyl). ) carbamate. At 25 ° C, 2.1 g (0.0205 mol) of triethylamine are added and the reaction mixture is stirred at 25 ° C for 5 hours. The precipitated product is filtered off, washed with chloroform and dried. 4.8 g of methyl N-3- [N- (3'-methylphenyl) carbamoyl] 7-phenylcarbamate are obtained. Sp. 146-148 ° C.

Example 2

However, the process of Example 1 is carried out using 50 ml of chlorobenzene by washing and the precipitated reaction product with chlorobenzene as the reaction medium. Yield 4.8 g, m.p. 146-148 ° C.

Example 3

However, the procedure of Example 1 is carried out using 50 ml of ethyl acetate as the reaction medium. After stirring the reaction mixture at 25 ° C for 5 hours, the solution is evaporated, the residue is suspended in toluene, the product is filtered off, washed with water and dried. Yield 5.0 g, m.p. 146-148 ° C.

Example 4 15.43 g (0.04 mol) of pentachlorophenyl N-phenylcarbamate and 7.24 g (0.04 mol) of ethyl N- (3-hydroxyphenyl) carbamate are added to 100 ml of ethyl acetate. After adding 4.2 g (0.0041 mol) of triethylamine to the reaction mixture, the mixture is stirred at 25 ° C for 5 hours. The solvent is distilled off and the residual oil is dissolved in 100 ml of warm benzene. After cooling, the precipitated crystals are filtered off, washed with benzene and dried.

11 g of ethyl N- [3- (N'-phenyl) -carbamoyl] -phenylcarbamate are obtained. Yield 91.8%, m.p. The starting material can be prepared as follows:

To a mixture of 27 g (0.1 mol) of pentachlorophenol, 13.1 g (0.11 mol) of phenyl isocyanate and 100 ml of toluene is added 0.8 ml of triethylamine at 25 ° C. The reaction mixture is stirred under ice-cooling for 3 hours at 25 [deg.] C., after which the precipitated product is filtered off, washed and dried. This gives 35.1 g of pentachlorophenyl N-phenyl carbamate. Yield: 90.5%.

Example 5 7.71 g (0.02 mol) of N-phenylcarbamic acid pentachlorophenyl ester and 3.62 g (0.02 mol) of N- (3-hydroxyphenyl) carbamic acid ethyl ester are added portionwise to 50 ml of ethyl acetate. At 25 ° C, 2.1 g (0.0205 mol) of triethylamine are added dropwise, then the reaction mixture is stirred for 5 hours at 25 ° C. The solution is evaporated, the residue is dissolved in 50 ml of benzene, the solution is cooled to 10 ° C and the separated product is filtered off. The precipitate is washed with 10 ml of benzene and dried. 5.5 g of N- [3- (N'-phenylcarbamoyloxy) -phenyl] -carbamic acid poethyl ester are obtained, m.p. 117-119 ° C.

Example 6 7.71 g (0.02 mol) of N-phenylcarbamic acid pentachlorophenyl ester and 3.34 g (0.02 mol) of N- (3-hydroxyphenyl) carbamic acid methyl ester are added portionwise to 50 ml of ethyl acetate. At 25 ° C, 2.1 g (0.0205 mol) of triethylamine are added dropwise, then the reaction mixture is stirred for 5 hours at 25 ° C. The solution is evaporated to dryness, the residue is suspended in 50 ml of chlorobenzene, then filtered. Wash with 10 ml of chlorobenzene and dry the product. 4.8 g of N- [3- (N'-phenylcarbamoyloxy) -phenyl] -carbamic acid methyl ester are obtained, m.p. 153-155 ° C.

Example 7 8.0 g (0.02 moles) of N- (m-tolyl) -carbamic acid pentachloro-6,61873 phenyl ester and 3.62 g (0.02 moles) of N- (3-hydroxyphenyl) -carbamic acid ethyl ester are added portionwise. ml of ethyl acetate. At 25 ° C, 2.1 g (0.0205 mol) of triethylamine are added dropwise, then the reaction mixture is stirred at 25 ° C for 5 hours. The solution is evaporated to dryness, the residue is suspended in 50 ml of toluene, then filtered. Wash with 10 ml of toluene and dry the product. 5.35 g of N- [3- (N '- (3'-methylphenyl) -carbamoyloxy) phenyl] -carbamic acid ethyl ester are obtained, m.p. 120-122 ° C.

Example 8 8.4 g (0.02 mol) of N- (m-chlorophenyl) -carbamic acid pentachlorophenyl ester and 3.34 g (0.02 mol) of N- (3-hydroxyphenyl) -carbamic acid methyl ester are added portionwise to 50 ml of ethyl acetate. At 25 ° C, 2.1 g (0.0205 mol) of triethylamine are added dropwise, then the reaction mixture is stirred for 5 hours at 25 ° C. The solution is evaporated to dryness, the residue is suspended in 50 ml of benzene, then filtered. Wash with 10 ml of benzene and dry the product. 4.9 g of N- [3-N1- (31-chlorophenyl) -carbamoyloxy) -phenyl] -carbamic acid methyl ester are obtained, m.p. 152-154 ° C.

Example 9 8.4 g (0.02 mol) of N- (m-chlorophenyl) -carbamic acid pentachlorophenyl ester and 3.62 g (0.02 mol) of N- (3-hydroxyphenyl) -carbamic acid ethyl ester are added portionwise to 50 ml of ethyl acetate. At 25 ° C, 2.1 g (0.0205 mol) of triethylamine are added dropwise, then the reaction mixture is stirred for 5 hours at 25 ° C. The solution is evaporated to dryness, the residue is suspended in 50 ml of xylene, then filtered. Wash with 10 ml of xylene and dry the product. 5.0 g of N- [3- (N '- (3'-chlorophenyl) -carbamoyloxy) -phenyl] -carbamic acid ethyl ester are obtained, m.p. 126-128 ° C.

Example 10 8.4 g (0.02 mol) of N- (p-chlorophenyl) -carbamic acid pentachlorophenyl ester and 3.62 g (0.02 mol) of N- (3-hydroxyphenyl) -carbamic acid ethyl ester are added portionwise to 50 ml of ethyl acetate. At 25 ° C, 2.1 g (0.0205 mol) of triethylamine are added dropwise, then the reaction mixture is stirred at this temperature for 5 hours. The solution is evaporated to dryness, the residue is dissolved in 25 ml of chlorobenzene, the solution is cooled to 10 ° C, the product is filtered off and washed. 10 ml of chlorobenzene and dried. 4.8 g of β- [β- (N '- (4'-chlorophenyl) -carbamoyloxy) -phenyl] -carbamic acid ethyl ester are obtained, m.p. 148-150 ° C.

Example 11 7.8 g (0.02 mol) of N-cyclohexylcarbamic acid anthachloro-7,61873 phenyl ester and 3.34 g (0.02 mol) of N- (3-hydroxyphenyl) -carbamic acid methyl ester are added portionwise to 50 ml of ethyl acetate. At 75 ° C, 2.1 g (0.0205 mol) of triethylamine are added dropwise, then the reaction mixture is stirred for 5 hours at 20 ° C. The solution is evaporated to dryness, the residue is dissolved in 25 ml of chlorobenzene and the solution is cooled to 10 ° C. The separated product is filtered off, washed with 10 ml of chlorobenzene and dried. 4.5 g of N- [3- (N'-cyclohexylcarbamoyloxy) -phenyl] -carbamic acid methyl ester are obtained, m.p. 159-160 ° C.

Example 12 6.4 g (0.02 moles) of N-methylcarbamic acid pentachlorophenyl ester and 3.62 g (0.02 moles) of N- (3-hydroxyphenyl) carbamic acid ethyl ester are added portionwise to 50 ml of ethyl acetate.25 ° C 2.1 g (0.0205 mol) of triethylamine are added dropwise and the reaction mixture is stirred for 5 hours. The solution is evaporated to dryness, the residue is dissolved in chlorobenzene, the solution is cooled, filtered, the precipitate is washed with 10 ml of chlorobenzene and dried. 4.0 g of N- [3- (N'-methylcarbamoyloxy) phenyl] carbamic acid ethyl ester are obtained, m.p. 128-130 ° C.

Claims (1)

A process for the preparation of N- (carbamoyloxyphenyl) carbamates of the formula I 0 / R 10 -CN 2 -R 2 (I) -NH-C-OR 3 - wherein R 3 is C 1 -C 4 -alkyl, C 3 -C 7 cycloalkyl or optionally halogen or a C 1 -C 4 alkyl-substituted phenyl group, R 2 is hydrogen or C 1 -C 4 alkyl, R 3 is C 1 -C 4 alkyl, characterized in that the carbamate having Formula III 9H (III) -NH-C-OR3 wherein R3 is as defined above is reacted in the presence of triethylamine with an ester of formula II Cl Cl V- / O Cl- <f V )> = T \ aJ Cl Cl R 1. 2 wherein R and R are as defined above.