CA1243676A - N-triazinyl carbonates - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
N-Triazinyl Carbomates of the formula III b

Description

~367~ 214~9-~337F

This Application is a divisional from Application 434,94 Eiled August 19, 1983.
Application 434,948 rela-tes -to a novel p~ocess for producing sulfonylureas having a herbicidal action and an a~ior regulatiny plant growth.
The sulfonylureas -to be produced by the novel process according to Application 434-948 are described together witn their properties in the United States Pa-ten-t Specifications Nos.
4,127,405, 4,301,286 and 4,302,241, and in the European Patent Applications Nos. 23422, 4~80~, 44808, 70802 and 72347.
The known processes, for these sulphonylureas, are dis-advantageous either because the process involves tne use of iso-cyanate or isothiocyanate derivates, the handling of which is difficult on account of tne high reactivity of tnis class of compounds or because ecologically undesirable by-products, for example phenols, occur during the synthesis from phenylcarbamates.
From the European Patent Application No. 514~5 there is known a process for producing similar sulfonylureas, with which process the above disadvantages are largely avoided. Sulfonyl-ureas are produced in this process by reacting a sulfonamide witha pyrimidinyl- or triazinylmethylcarbamate in the presence of at least e~uimolar amounts of trimethylaluminium. This process is disadvantageous in that the trimethylaluminium used is pyrophoric, and is furthermore decomposed by air and moisture.
Application ~34,9~8 provides a process which avoids the use of compounds which are difficult to handle, and also tne occur-rence of environmentally unfavourable by-products.

~' , ~3676 Applica-tion 434,948 discloses -tha-t surprisinyly the reaction of sulfonamldes with alkylcarbamates can also be per-formed wi-thout trialkylaluminium.
It is thus suyyes-ted accordiny to Applica-tion 434,948 -that the herbicidal and plan-t-growth-regulating sulEonylureas o the general formula I

X

G-S02-NH-CO-NH- ~ ~ Z (I) N=-/

wherein G is a radical of the formula ' 2 ._.~
Rl --t~ or ~ ._ ~ A'~ R3~ .--.

X is Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-alkylthio, Cl-C4-haloalkoxy, Cl-C4-alkylamino or di-Cl-C4-alkylamino, Y isCl-C4-alkyl~Cl-C4-haloalkyl, Cl-C4 -alkoxy or Cl-C4-haloalkoxy, and ' :1~436~6 Z is nitrogen or the methine bridge, A is oxygen, sulfur, -NR5- or -C=N-, R5 being hydrogen, Cl-C4-alkyl or -CO-Cl-C4-alkyl, Rl is hydrogen, halogen, nitro, -Q-Cl-C4-alkyl, cl-C4-alkyl, CF3, -S02-di-Cl-C4-alkylamino~
-CO-Q-C3-C5-alkynyl, or -CO-Q-Cl-C4-alkyl or -CO-Q-C3-C5-alkenyl each unsubstituted or substituted by halogen, cyano, Cl-C4-alkoxy or Cl-C4-alkylthio, R2 is hydrogen, halogen, CF3, N02, cl-C4-alkyl or cl-c4-alkoxy, R3 is hydrogen, fluorine or chlorine, R4 is hydrogen, halogen, nitro, CF3, Cl-C4-alkyl, -CHR6R7, -S02-di-Cl-C4-alkylamino, -Q-C3-C5-alkynyl, -CO-T-C3-C5-alkynyl, or -Q-Cl-C4-alkyl, -Q-C2-C5-alkenyl, -CO-T-Cl-C4-alkyl or -CO-T-C3-C5-alkenyl each of which is unsubstituted or substituted by halogen, cyano, Cl-C4-alkoxy or Cl-C4-alkylthio, Q being oxygen, sulfur, ~SOn~, -NH- or -N(Cl-C4-alkyl)-, n being zero, one or two, and T being an oxygen, sulfur, -NH- or -N(Cl-C4-alkyl)- bridge, R6 is hydrogen, chlorine or methyl, and R7 is chlorine, cyano, methoxy, ethoxy or -SOn-Cl-C4-alkyl, be produced by reacting a sulfonamide of the formula II
G S02 NH2 (II), wherein G has the meaning defined above, with an N-pyrimidinyl- or N-triazinylcarbamate of the formula III

R-O-C-NH~ Z (III) ll \ N ~
o r wherein X, Y and Z have the meanings defined above, and R is methyl or e~hyl.

,.~, ,,, .. ' ~

~;~43~7~

By halogen is meant within the scope of the above definition in general fluorine, chlorine, bromine or iodine, fluorine and chlorine being preferred. Preferred as substituent of the radical G is particularly chlorine;
and as substituent oE an alkyl group, which in its turn can be part of a radical, especially ~luorine.
~ xamples of alkyl are: methyl, ethyl, n-propyl and i-propyl or the isomeric butyl groups. Alkyl is itself to be understood as being a substituent or as part of another substituent, for example alkoxy or alkylthio.
Pre~erred alkyl groups are in each case unbranched alkyl chains, especially however methyl and ethyl.
Preferred substituents of the radical G among the 1' ~2' R3, R4 and R5 are those selected from the group comprising: chlorine, methoxycarbonyl, nitro, dimethylsulfamoyl, trifluoromethyl~ methylsulfonyl and n-propylsulfonyl.
By alkenyl is meant as a rule: allyl, 2-butenyl, 3-butenylg 2-isobutenyl, isopropenyl, 2-pentenyl, 3-pentenyl and 4-pentenyl, particularly allyl and 4-pentenyl.
By alkynyl is meant in general: propargyl, 2-butynyl, 3-butynyl, methylpropargyl, 2-pentynyl, 3-pentynyl and 4-pentynyl.
The heterocycles which are covered by the definition of the radical G are: thiophene, furan, pyrrole and pyridine.
Preferred pyrimidine and triazine rings are those ln which X is methyl, ethyl, fluoromethyl, trifluoromethyl, methoxy, ethoxy, i-propyloxy, methylthio~ chlorine, bromine, difluoromethoxy, 2,2,2-trifluoroethoxy, methylamino or dimethylamino, and Y is methyl, methoxy or difluoro-methoxy.

~, ,,. .

. . ~ - . .

.
- "
- - ~
~.. , ~ . ~ -;
:.

' ~Z436'^/~;

The carbamates of the formula III are reacted with the sul~onamides of the formula II by heating the mix~ure of both reactants until a detachment of the alcohoL
occurs. The reaction can be performed either wi~hout solvent or in the presence of an inert solvent. The reaction mixture is generally heated up until the reaction in which the alcohol is detached commences, and is held at this temperature until a complete conversion has been obtained. The temperature is as a rule 20 to 200C, preferably 40 to 100C. Solvents which have proved suitable are: hydrocarbons, such as benzene, toluene, xylene, mesitylene, tetrahydronaphthalene, decalin, cyclohexane and higher-boiling ligroin fractions; ethers, such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, diethyleneglycoldimethyl ether and diphenyl ether;
nitriles, such as acetonitrile or propionitrile, ketones, such as ethyl methyl ketone, cyclohexanone and acetone;
amides, such as dimethylformamide or N-methylpyrrolidinone and dimethyl sulfoxide.
The addition of a base frequently proves advantageous in the reaction according to the invention. Particularly suitable bases for this purpose are: l,5-diazabicyclo 14,3,0~ non-5-ene (DBN) or l,5-diazabicyclo 15,4,0) undec-5-ene (DBU). The reaction temperatures are as a rule between 20 and 200C, preferably between 40 and 100C.
In a preEerred embodiment of the process according to Appli-ca~i~n 434,948 the procedure therefore comprises heating a sulfonamide of the formula II, in the presence of a base, with a carbamate of the formula III in an inert solvent at 40 to 100C until the reaction in which the alcohol is detached is completed, and then isolating the product.
The starting compounds of the formula II are known or can be produced by methods analogous to known methods.

.
-' ~

, . . . .
' ' .:

43~

The N-pryrimidinyl- and N-trlazinylcarbamates of the formula III are in part known. They are produced by reaction of the aminopyrimidines or -triazines of the formula IV

X

~ N~.~
H2N-~ ~ (IV~, N=~

wherein X, Y and Z have the meanings defined in the foregoing, with a carbonic acid ester of the formula V
R - O - CO - OR (V), or with a chloroformic acid ester of the formula VI
Cl - CO - OR (VI), wherein R is methyl or ethyl.
Novel N-pyrimidinyl carbamates correspond to the sub-formulae IIIa X
N- ~
R-O-C-NH-~ ~ (IIIa), li \ /
O N-wherein R, X and Y have the meanings defined under the formula III, with the proviso that R is ethyl when at the same time Y is methyl and X is methoxy. These N pyrimidinylcarbamates of form-ula IIIa have been developed specially for the synthesis of the active substances of formula I according to the process of Application 434,948~
Similarly, the N-triazinylcarbamates of the :Eormula IIIb . .

' .
.
- :
-.

~6a-~L3~;7~

O-alkyl N. ~
R-O-C-NH- \N (IIIb) Il ~ /
O N = ~
c~3 nave also been developed specially for -the syntllesis of the acti.ve substances of formula I according to the process of Application 434,948.
Thus in its broadest aspect this invention provides N-Triazinylcarbamates of the general formula IIIb O-alkyl N-~
R-O-C-NH- \ N (IIIb) O N=~ ~

wherein R is methyl or ethyl, and alkyl is Cl-C4-alkyl.

In a second broad aspect this invention provides a pro-cess for the preparation of N-triazinylcarbamates of tne general formula IIIb O-alkyl ~N-.~
R-O-C-N~-~ N (III~) O N=~ ~

wnere~n R is methyl or etnyl, and alkyl is Cl-C4-alkyl W~iCil process comprises reacting a silylaminotriazine of the formula (VIIIb) , 36~6 -6b-O-al~yl ~_.
(CH3)3Si-NH- N (VIIIb) N=.\

in which alkyl i5 as defined above, with a chloroformic ester of the formula Cl-CO-OR in which R is a methyl or ethyl group.
Particularly preferred compounds of this class are:
N-(4-methoxy-6-methyl-1,3,5-triazinyl-2-yl)methyl carbamates;
and N-(4-methoxy~6-methyl-1,3,5-triazin 2-yl) ethylcarbamate.

.

. .

. . ~

~43~

According to the process of Application 43~,948 the reaction of the aminopyrimidines and -triazines of the formula IV
with the carbonic acid esters of the formula V or with the chloro-formic acid es-ters of -the formula VI can De perfo~me~ in the pre-sence of a suitable inert apro-tic solvent, or in the absence of a solvent. The use of a solvent has however proved advantageous.
Suitable solvents are: hydrocarbons, such as benzene, toluene and xylene; ethers such as diethyl ether, ethylene glycol dimethyl etner, diethylene glycol dimethyl ether, tetrahydrofuran and dioxane; ketones, sucn as acetone, ethyl methyl ketone and cyclo-hexanone;and nitriles, such as acetonitrile and propionitrile.
The reaction is performed in the presence of at least equimolar amounts of a base. Suitable bases are carbonates, such as sodium and potassium carbonate, hydrogen carbonates, sucn as sodium and potassium hydrogen carbonate, oxides, such as calcium and magnes-ium oxide, and tertiary amines, such as trimethylamine, trîethyl-amine, quinuclidine, quinoline, pyridine and tripropylamine. The base is advantageously used in excess. There are thus preferably used 1 to 5 mols of base, especially 1.1 to 1.5 mols, per mol of sulfonamide. Laryer excesses of base are used in particular wnen the reaction is performed witl~out solvent, and the base, prefer-ably a liquid tertiary amine, simultaneously serves as reaction medium. The reaction temperatures are as a rule between 0 and o o 140 C, preferably between 10 and 80 C.
It can in some cases be advantage~us ts produce the aar-bamates of the formula III not by the process outlinea ...... , :

.. . .

~Z~367~ ~

above but by the following process in order to obtain a higher yield. The N-pyrimidinyl- and N-triazinyl-carbamates of the formula III are accordingly produced by converting an aminopyrimidine or -tr-lazine o~ the formula III with a silylating agent in~o the silylamino-pyrimidines or -triazines of the formula VII

(CH3)3 Si - N~ Z (VII), and reacting these with the chloroformic acid esters of the formula VI.
Silylation is customarily per~ormed by heating the aminopyrimidine or -triazine together with the silyla~ing agent, such as N,0-bis-~trimethylsilyl)-acetamide, hexamethyldisilazane or trimethylchlorosilane, optionally in the presence of a catalyst, such as concentrated sulfuric acid or hydrogen chloride, in an inert solvent at 30 to 150C, preferably at 40 to 80C. Suitable solvents are: hydrocarbons, such as benzene, toluene and xylene; ethers, such as diethyl ether, ethylene glycol dimethyl ether, diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran and dioxane; nitriles, such as acetonitrile and propionitrile; and dimethyl sulfoxide.
The further reaction of the silylaminopyrimidines or -triazines o~ the formula VII with the chloroformic acid esters of the formula VI to the N-pyrimidinyl- and N-triazinylcarbamates of the formula III is performed by heating at 30 to 120C, preferably at 40 to 80C. This reaction can be carried out without solvent or in an inert solvent, for example benzene, toluene, xylene, petroleum ether, cyclohexane, diethyl ether, dioxane or tetrahydrofuran.

. ~' :.

-9- ~z~3~7~

Tne process ~or produciny the intermediates of -the form-ula VII and also these intermediates are novel, and have been developed specially for the procluction process according -to Application 434,948.
The starting material of the formulae V and ~ are known and are ob-tainable comrnercially.
The followin~ Examples serve to further illustrated tne present invention.
Example 1: N-(2-Chlorophenyl-sulfonyl)-N'-(4-methoxy-6-methyl-1, 3,5-triazin-2-yl)urea.
A mixture of 1.3 g of 2-chlorophenylsulfonamide, 1.0 g of N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)-methylcarbal-nate and 1.O g of 1,5-diazabicyclo ~4,3,0~ non-5-ene in 10 ml of dioxane is stirred for 14 hours at 100C. After the addition of 50 ml of water, the mixture is acidified with 10~ hydrochloric acid and extracted with ethyl acetate. The organic phase is concentrated by evaporation, and the residue is crystallised from~ a methylene chloride/ether mixture to thus obtain 0.75 y of N-(2-chlorophenyl-sulfonyl)-~l~'-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)-urea, m.p.
176-178 C.
Example 2:
a) 4-~ethoxy-6-methyl-2-trimethylsilylamino-1,3,5-triazine.
A mixture of 238.2 g of 2-amino-4-methoxy-6-methoxy-6-methyl-1,3,5-triazine, 505 ml of N,O-bis-(trimethylsilyl)~acetamide and 1150 ml of anhydrous acetonitrile is refluxed Eor 8 hours.
Fractional dis-tillation yields 296.4 g of 4-rnethoxy-6-methyl-2-trimethylsilylamino-1,3,5-triazine, b.p. 78 C/0.053 mb.

~;~4~676 b) N-(4-Methoxy-6-methyl-1,3,5-triazin-2--yl)-methylcarbamate A mixture of 10.6 g of 4-methoxy-6-methyl-2~
trimethylsilylamino-1,3,5-triazine and 14.2 g of chloroformic acid methyl ester is stirred for 20 hours at 65C. The volatile consti~uents are evapor~e~ of in vacuo, and the resldue is taken ~lp with 3V ml of methylene chloride. After separation of the insoluble constituents, the solution is concentrated by evapora~ion and the residue is chromatographed on silica gel. The yield is 6.2 g of N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)-methylcarbamate, m.p. 102-104C.
Example 3: 4-~ifluoromethoxy-6-methyl-2-trimethylsilyl-pyrimidine.
A mixture of 21.0 g of 2-amino-4-difluoromethoxy-6-methyl-pyrimidine and 0.27 ml of concentrated sulfuric acid is heated in 90 ml of anhydrous toluene to 60C, and a mixture of 12.5 ml of hexamethyldisilazane and 7.6 ml of trimethylchlorosilane is added within 10 minutes.
The formed suspension is stirred at 60C for 24 hours;
it is subsequently cooled to 20 to 25C, filtered and fractionally distilled. The yield is 26 g of 4-difluoro-methoxy-6-methyl-2-trimethylsilyl-pyrimidine, b.p. 95C/ll mb.
Example 4:
a) 4-Methoxy-6-methyl-2-trimethylsilylamino-pyrimidine.
A mixture of 27.9 g of 2-amino-4-methoxy-6-methyl-pyrimidine and 48.8 g of N,0-bis-(trimethylsilyl)-acetamide in 250 ml of acetonitrile is refluxed for 7 hours. After cooling, the insoluble sediment is separated off and the filtrate is fractionally distilled. The yield is 36.3 g of 4-methoxy-6-methyl-2-trimethylsilylamino-pyrimidine, b.p. 62-64Oc/o.026 mb.
b) ~-(4-~ethoxy-6-methyl-pyrimidin-2-yl)-methylcarbamate.
A mixture of 10.6 g of 4-methoxy-6-methyl-2-trimethyl-silylamino-pyrimidine and 47 g of chloroformic acid methyl ester is stirred in 120 ml of petroleum ether at 50C for 7 hours. As the solution cools, 5.5 g o N-(4-methoxy-6-methyl-pyrimidin-2-yl)-methylcarbamate, m.p. 92-95C, crystallise Ollt.
The intermediates listed in the following Tables are obtained in an analogous manner.
Table 1:
~N- .

R-O-CO-NH

No. R x z Physical data 1.1 CH3 OCH3 CH3 N m.p.102-104C
1.2 CH3 OCH3 OCH3 N
1.3 CH3 OCH3 CH3~ CH m.p.92- 95C
1.4 CH3 OCH3 OCH3 CH
l.S CH3 CH3 CH3 CH m.p.96-98C
1.6 CH3 CH3 CH3 N
1.7 CH3 OCHF2 CH3 CH
1.8C2H5 OC~F2 CH3 CH m.p.86-89~C
1.9 CH3 OCHF2 OCH3 CH
1.10CH3 OCHF2 OCHF2 CH
1.11C2115 OCH3 CH3 N m.p.73-74C
1.12C2H5 OCH3 OCH3 N
1.13C2H5 OCH3 CH3 CH
1.14C2H5 OCH3 OCH3 CH
1.15 C2H5 CH3 CH3 CH m.p. 68~69C
1.16 CH3 C2H5 CH3 N

Table 2:
N--/
(C113)3Si - NH - ~ ~Z
N=.

No . X Z Physi cal data~

2.1 OCE~3 3 N b.p. 78C/0.053 mb 2.2 OCHF2 CH3 Cll b.p. 95C/ 11 mb 2.3 OCH3 CH3 CH b.p, 62-64C/0.026 mb 2 . 4OCH3 OCH 3 N
2.5 OCH3 CH 2 F CH
2.6 0cHF2 CH3 N
2 . 7OCH3 OCH3 CH
2. 8 CH3 CH3 N
2. 9 CH3 CH3 CH
2 .10OCHF2 OCH~ CH
2.11OCHFzOCI;Fz ~ CH ~ ~ _ . .

:

Claims (3)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. N-Triazinylcarbamates of the general formula IIIb (IIIb) wherein R is methyl or ethyl, and alkyl is C1-C4-alkyl, provided that both alkyl and R are not simultaneously methyl.

2. N-(4-Methoxy-6-methyl-1,3,5-triazin-2-yl)ethylcarbamate.

3. A process for the preparation of N-triazinylcarbamates of the general formula IIIb (IIIb) wherein R is methyl or ethyl, and alkyl is C1-C4-alkyl which process comprises reacting a silylaminotriazine of the formula (VIIIb) (VIIIb) in which alkyl is as defined above, with a chloroformic ester of the formula C1-CO-OR in which R is a methyl or ethyl group.