CS219932B2 - Method of making the derivatives of the phenylester of the carbamic acid - Google Patents

Description

The invention relates to a process for the preparation of carbamic acid phenyl ester derivatives by acylation of the corresponding phenols. :

^Fe.nylester^y carbamov^E to^yselins extractable from^p& obem^pO^dle v^yn^álezu o^dpcontrol the village formula I

R ¹ __

4z · O-C-NH-R o

i (() wherein R is alkyl of 1-8 carbon atoms, aryl group having 6 to 10 carbon atoms, 'cyclohexyl, or aralkyl of 7 to 16 carbon atoms and at least one alkyl group having 1 to ⁴ atom of ^Y atoms substitoované ^d Eriva ^y Uve ^d enýc ^h s ^to u ^when the ^R1 is as ^thanks ^ alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms or alkoxycarbonylamino of 1 to ⁴ carbon atom ^s tue ^ that R ² represents hydrogen ^ ^h allogenic, alkyl having 1-4 carbon atoms or and ^o ox ^y íovou skuprnu 1 ^{and 4} carbon Uhl ^{Cart u, p} o ^{p at} pH Ada as asylum and / or ^ and ^o ox ^yl OV ^E Cupin ^y of ^R1 and ^R2 with ^p Ojén circle C-C bond.

Most of the compounds of formula I find use in agriculture as a plant protection agent.

It is generally known that the compounds of the formula I are generally produced by the addition of an isocyanate of the formula III

R-N = C = O (ΠΙ) · on the phenol derivatives of formula II (II) e R ^{kd R1} and ^R2 are ^H with Ora Uve ^d Eny importance. No ^d OTHER ITEMS ^to em Uve ^d eného ^PU Sobu ^ Nost fact is that the strongly toxic isocyanates invading the mucosa, causing problems of safety and health, thereby greatly complicates the technological process. A drawback is also strongly exothermic nature of the addition reaction, causing - in particular for Isoka ^{An y} t is a temperature ^of the low boiling - ^d other technological problems popřpadě creates mož219932 course alternatives for unwanted side reactions. Transport and storage of certain iso ^{to Yan} t ^ ^u require specmlr measures ^and peciální packaging, which causes additional costs. Ly ^from Nost opatřern isocyanates in ^the World limited scale.

· Compounds of formula I may be Prince ^pial them Rab ^{characterized} in that ^{f E} t rea ^the CI with the compound of formula II with a chloride polysubstituted ^yk r ^{b s} amic ^alkyl Sehn ^y. Polysutatftuo-va ^ -carbamic acid chlorides are however - - unlike their disubstituted by ^Gu ana ^l - ^ worth substances which disintegrate after delamination HCl to isocyanates. This is not enough compound ^Y may give rise to ^T t ^Ez addition of HCl to isocyanates, but can not count on being able to be acylated with a nucleophilic agent such as a compound of formula II, without prior cleavage hydrochloric ^thanks u. No ^d OTHER ITEMS ^alkyl Uve ^d en ^E in relation to with isocyanates, they also persist with monosubstituted carbamic acid chlorides.

Another possibility for preparing compounds of formula I is the reaction of compounds of general formula II · with phosgene and subsequent acylation of the obtained derivates · · chloroformate ester with amine ^{characterized} by the general formula ^{H k d} · e

R 6 is as defined above. The disadvantage of this method is the need to work with extremely toxic phosgene.

It has now been discovered that derivatives of ^the phenyl esters artiamov ^{E, K y} a ^b Yssel ECN it ^{é l} of Formula I ^{characterized} by the ^Abeta r ^o s čistorá and good discharge a manner that the phenols of formula II

^kd e ^R1 and ^R2 are ^s Staa Uve ^d Eny ^meaning, c ^ tallow ^as derivatives of ^N - ^{k y} arbamo lsacharmu formula IV

^kd e ^{r e} above ^meanings, in the presence of a base.

As the base, inorganic base ^of names hydroxides alkahckých ^to ov carbonates and hydro ^g enuhličitany ^{h y} droxid ^yk ov alkahckých earth ^ jejmh carbonate, ^y and hydro-nuhhííhan ^ and ^AK t ^{EZ ORG} anmké ^base I ^to the Termar amine ^ ^é especially for triethylamine. The base-only, at least in equimolar amount lárrnm mod ^{T and} ENO · AC ^yl and ^No. činidlQ · ^rn,

The reaction of the compound of formula II with the compound of formula IV is carried out in an organic solvent or in an aqueous-organic solvent medium. Suitable organic solvents are hydrocarbons, ^five lower ketones or esters (acetone, methylethylketone, ethyl acetate), ethers (dioxane, tetrahydrofuran), chlorinated hydrocarbons (chloroform, dichloroethane), lower acid amides (formamide, dimethylformamide). Preferably solvents are used, which is soluble in at least one of the starting materials and bases resulting compound of formula I but is not soluble or is · in the solution in a · form that during its precipitation fall out together different ^components recited. PH use Anor ^g anic ^to YC ^HB to ^{I PURPOSE} for purifying the product, if necessary, is suspended in water. In view of the fact that the salt adducts formed from organic bases are soluble in organic solvents, it is preferable to use organic bases, especially in systems in which the resulting compound of formula I is insoluble, whereas the organic base and the s-acharin adduct are · Soluble.

The reactions of the compounds II and IV can be carried out at temperatures of 0 to 100 ° C. The reaction at room temperature is preferred. The resulting final · products · are preferably separated by crystallization or vystrážením suitable solvent such as saccharin, cleaved at REA ^ n ziastává in the ^f orm ^of their SOH with ingrained and optionally can be easily separated and reused to produce _ · acylating agent of formula IV.

The novelty of the method consists in the fact that the compounds ^No. enyne ^Y General ^eh O · Formulas ^I 'still data in the ^y Robit ^p nly N nfoi reatoemú or restricted two-stage substitution reactions, whereas the method according to the invention Manufacture · compounds · formula I · . proceeds in one step by a substitution reaction. This makes it possible to produce compounds in an aqueous environment.

The process according to the invention is also advantageous in that toxic liquid or solid acylating agents are not used in comparison with the known processes. N-carbamoylsaccharin derivatives are simple crystalline compounds ^that are easy to store and handle. Are undertaken acyl ^L AČN ^s rea tion ^to M ^{E ka} no exothermic not ^of example, the reaction of isocyanates. This does not cause harmful side reactions and the compounds of formula I can be obtained with high purity and good yield.

^In yn ^AL ez is ^further illustrated by the e bhže záMadě examples.

P1 ^ l <^ d [l

4.3 g (0.025 mol) of methyl N- (3-hydroxyphenyl) carbamate is reacted 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-phenylcarbamoylbenzoic acid sulfimide (tt). 184-186 ° C) at 40 ° C for 15 minutes. K reac

Water (40 ml) was added to the mixture and cooled to 5-10 ° C. After half an hour the product is filtered, ^p rom ^y and ^{d y} sus. 5.5 ^{g of} 3-methoxycarbonylaminophenyl-N-phenylcarbamate, m.p. 150 DEG-152 DEG C., are obtained. Benzoic acid sulfamide 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-ol are reacted in ¹⁵ ml of acetone in the presence of ^2.56 g ( ^0.025 mol) of triethylamine and 6 g (0.025 mol) of sulimide N ^yl methylcarbamate lbenzoové acid at 50 ° C for 15 minutes. The reaction mixture was diluted with 100 mL of water and cooled to room temperature. The precipitate formed is filtered off, washed with water and then dried. 3.1 g of ^{2,3-dihydro-2,2-djinethylbenzofuran-7-yl-N-meth o} r ^b У ^{AM herein for} esters melts at ^150-152 ° C. The benzoic acid sulfide can be reacted from the mother liquor by acid precipitation.

Example 3

1.5 g of N-sulfimide methylkarbamoylbenzoové acid are suspended in a mixture of 1.0 g of 2,3-dihydro-2,2-dimethylbenzofuran-7-ol, acetone and 5 .ml п ¹ in ^soil. Pn te ^pl OTE room -for added dropwise with stirring over 20 minutes ⁰ 6 ^g trieth.ylammu ^span t ^{e d} it in a mixture ^of 2 mL of acetone and 1 mL water. 20 ml of water are then added dropwise to the reaction mixture over 30 minutes. After 1 l./2hoďinov mucltem m ^s r ^{s to} become filtered, washed with water and then dried. This gives 0.745 g of 2,3-dihydro-2,2-dimethylbenzo-furan-7-yl-N-methylcarbamate, which melts at 150-152 ° C.

Example 4

4.3 g (0.025 molu- methyl - N ([3-hydooxyferryljkarbamáfu is locally hosted in ¹⁵ m ¹ of acetone in the presence of 2 g [0.0145 mol) of potassium drasebPio ^{7.3 g of (0} ° 25 mol) of N sulfimide -fenylkarbamoylbenzoové acid (mp ^184-186 ° C) for 15 mrnth reflux. to the reaction mixture was added ⁴⁰ m ^{1 y} and octaach water at ^{55 and 10} ° C. after one hour, the precipitate was filtered, washed and dried. 5.8 g of 3-methoxycarbamino-4-aminoiminophenyl-N-phenyl-alaphamate are obtained, which melts at 150 to 152 ° C.

Example 1 a d 5

4.5 g (0.025 mol) of ethyl N- (3-hydroxyphenyl) carbamate are reacted 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-phenylcarbamoydbenzoic acid sulfimide at ⁴⁰ ° C ^p I for a period ^{of 5} minutes. After NDAN ^{p 4} 0 ml of water, the mixture was cooled to 5 ° C. After 30 min of standing, the product was filtered, washed and dried. 5.7 g of 3-ethoxycarbonyl-cannula aminophenyl-N-phenylcarbamate, which melts at 117-119 ° C.

Example 6

4.3 g of 00.025 methyl methyl N- (3-hydroxyphenyl) carbamate are reacted in 15 ml of acetone in a darkness of ^{2.56 g} (0-5 mol) of triethylamine with 7.9 g (0.025 mol) of N-sulfimide. (3-methylphenyl) carbamoylbenzoic acid at 30 ° C for 30 minutes. After adding 50 ml of water, the mixture is cooled to 5-10 ° C. After standing 30 minutes, ¹ odfiltruee product, washed and dried. 5.3 g of 3-IIWthrxykaгbamoylienyl ³ -nluthy] phenylcarbamate which melts at 140-142 ° C. The mother liquor can be recovered by precipitation ^to yselmou c ^{h s} lrrrvod metal ^{(3.5 g, 76%)} suhimidu benzoic acid. This is possible in all the above examples.

Example 7 g of N-sulfimide methylkarbamoylbenzrové acid are suspended in a mixture of 2.67 g of ^2-F chlrr ENR ^d u ¹ Acetone ⁵⁰ m, the suspension was cooled to 5 ° C and then under stirring stálého- added dropwise a solution of 2, 9 g of triethylamine in 30 ml of acetone. - The temperature of the mixture does not exceed 6 ° C during the addition (2 hours). The reaction mixture is stirred at this temperature for 12 hours and then 240 ml of distilled water are added. The mixture was then extracted three times with 30 ml of ether. The combined ether extracts were dried over anhydrous sodium sulfate and then evaporated in vacuo at no more than 30 ° C. 3.13 g of 2-chlorophenyl N-methylcarbamate are obtained, which, after recrystallization from n-pentane, melts at 90-91 ° C.

EXAMPLE 8 g sulfimide Nlmethylkarbamoylbenzrl ove ^alkyl selrn ^y are suspended in a mixture of ^{2.6 g of} 2 ^^^ MDHO: ^^^: phenol and 50 ml of acetone. With stirring, a solution of 2.9 ml of triethylamine in 30 ml of acetone is added dropwise at room temperature over a period of - 1 hour. The reaction mixture is stirred for an additional 2 hours at room temperature and then 240 ml of distilled water are added. The mixture is extracted three times with 30 ml of ether each time. The combined ether extracts were dried over anhydrous sodium sulfate and then evaporated in vacuo at no more than 30 ° C. 2.43 g of 2-methoxyphenyl-N-methylcarbamate are obtained, which, after recrystallization from n-pentane, melts at 90-92 degrees Celsius.

Example 9

2.4 g of N-sulfimide methylkarbamoylbenzoové acid are suspended in a mixture of 1.63 g of 2-methoпотеethylenfenolu -a ⁵ m ¹ I of acetone. While sweeping, ^a solution of 1.4 ml of triethylamine is added dropwise ^{to the} suspension at room temperature over one hour.

L

in 5 ml of acetone. The mixture was stirred for an additional 2 hours at room temperature and then 65 ml of distilled water was added. The mixture was allowed to stand for 16 hours at 5 ° C, then the precipitated 2-methoxy-4-cyanomethyl lenfen ^{y y} LN-methylcarbamate filtered off, ^and the water rom ^y is ⁵ ° C ou te ^pl. 0.72 g of product is obtained, melting at 138-139 ° C; Analysis:

Calculated:

C ⁵⁹ H 99% ⁵ 45% 12.72% N Found:

C ⁶⁰ 05% H '5 ^52% N ¹² 65%.

The mother liquor was washed three times with 10 ml ether, the combined ether extracts were dried over anhydrous sodium sulfate and is evaporated in ^the highest uu pn ^{e 30} ° C. ^Ka is the ZIS ^to a further 0.95 g of product.

Example 10 ^{5 g of N} sulfimtéu - ^{-Butyl lk} arbamoylb3nzoov ^s acid are suspended in a mixture of 1.67 g of phenol and 50 ml of distilled water. To the suspension was added dropwise at room temperature with constant stirring it for 5 hours with 0.71 g NaOH ^with copper in 50 ^ld estnovan ^é water. Reakišní ^with m ^E is mfclm da ^LSI tn ^h arrayed then extracted tnkr ^á T ³⁰ M ^L et ^h interruption and linked exfakty in ^y su ^{width b} ezvodým sodium sulfate to ^p e ^z is odpan vacuum pn more than 30 ° C. Yield phen ^y ln -but ^yl dimethylcarbamate, its boiling point is 145-148 ° C / 270 mbar.

Example 11 g of ^N -terc. ^b ut ^yl carboxylic ^{b y} amo lbenzoové ^alkyl Selin ^y and 1.9 g of ^{4-methylbenzyl} lfenodu ^y are heated in 50 ml of chloroform to the boiling temperature. Then there are added while stirring over one hour, 2.5 ml of triethylamine in ³⁰ m ^l of chloroform drops ^and CH. The mixture was then boiled for one hour and evaporated in vacuo. The oily residue is stirred with 100 ml of ether. The resulting triethylamine salt of benzoic sulfimide is filtered off and the filtrate is evaporated under vacuum at not more than 30 ° C. 2.4 g of ^{4-methyl-phenyl-l} - ^{yl N} -terc.but ^karhamátu,. which melts after recrystallization from petroleum ether at 130-132 ° C.

Claims (4)

CLAIMS 1. A process for the preparation of carbamic acid phenyl ester derivatives of the general formula (I) (I) wherein R represents an alkyl group having 1 to 8 carbon atoms, an aryl group having 6 to 10 carbon atoms, a cyclohexyl group or. aralkyl of 7 to 16 carbon atoms and at least one alkyl group having 1 to 4 carbon atoms substituted by ^Star deruta Uve enýc ^{d h} s ^to u ^{when n} .atom ^R1 hydrogen, alkyl having 1 to 4 carbon atoms, alkoxy C 1 -C 4 or C 1 -C 4 alkoxycarbonylamino, R 2 is hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, optionally as alkyl and ^/ or atheoxy groups ^P ins of ^R1 and ^R2 with ^p to ^{y Ojen;} ring by a ^C-C -acylací phenol derivatives of formula II wherein ^R1 and ^R2 have the previously listed ^d Eny ^meaning, characterized in that used for the acylation of N-karbamoylsacharinu of formula IV wherein R has the above meanings, in the presence of a base in an organic solvent or in an aqueous organic solvent or water. ^2. is treated with ^p ccording ^b o ^d u 1 ^y ^ marking ^the acylation is carried out in the presence of at least equivalent amount of base, based. to an acylating agent. 3. Method according to claim 2, characterized in that ^the použj anorgarnc é ^{b Aze,} especially for hydroxy ^ ^é uhlmhany hydrogenuhnčhany and alkali metal hydroxides, carbonates and liydrogenuhličitany alkaline earth metal, or a tertiary amine base, especially triethylamine. ⁴ . ^{From the} mouth after ^{dL b} e ^{d b} of about 1 ^and 3 significant that the acylation is carried out at temperatures between 0 and ⁰⁰ ° ^from L C esp ^s PN mfctnostl