Process for the preparation of carbamate derivatives

A process for the preparation of a compound of the formula: ##STR1## wherein R.sup.1 is alkyl, alkyl substituted by halogen, alkyl substituted by alkoxy, aryl, aryl substituted by halogen, aryl substituted by alkyl, aryl substituted by alkoxy, aralkyl, aralkyl substituted by alkoxy, cycloalkyl, cycloalkyl substituted by halogen, cycloalkyl substituted by alkyl or cycloalkyl substituted by alkoxy, and PA1 R.sup.2 is an aromatic group, an aromatic group substituted by alkyl, an aromatic group substituted by halogen, an aromatic group substituted by alkoxy, a heteroaromatic group, a heteroaromatic group substituted by alkyl, a heteroaromatic group substituted by halogen, or a heteroaromatic group substituted by alkoxy, by the reaction of phosgene with a phenol of the formula: EQU R.sup.2 -OH and further by the reaction of a primary amine of the formula: EQU R'--NH.sub.2, reacting all three of the abovementioned reactants solution in a common water-immiscible organic solvent in the same reaction vessel at the same time in the presence of an acid binding agent to yield the compound of formula ##STR2##

This invention relates to the substitution of phenolic hydroxy groups in 
organic compounds by an alkyl-, cycloalkyl-, aralkyl-, or aryl-carbamoyl 
group, which comprises introducing phosgene into a solution containing an 
organic compound bearing a phenolic hydroxy group and a primary 
alkylamine, cycloalkylamine, arylamine or aralkylamine, preferably in the 
presence of an acid binding agent. 
The compounds prepared according to the present invention are useful in 
organic chemistry as pesticides. 
The following compounds prepared according to the present invention are of 
outstanding importance: 
1-methyl-2-[1,3-dioxolane-2-yl]-phenyl-N-methyl-carbamate as a pesticide. 
According to the state of prior art these compounds were generally prepared 
by reacting a compound containing a phenolic hydroxy group with the 
corresponding isocyanate or reacting the corresponding urethane with an 
amine. According to a known process a compound containing a phenolic 
hydroxy group is reacted with phosgene and the chlorocarbonyl derivative 
thus obtained is reacted with an amine [e.g. German Patent No. 1,745,784]. 
According to another method the amine is reacted with phosgene and the 
carbaminic acid chloride thus obtained or rather the isocyanate formed 
when the latter compound is reacted with a phenol. Such a solution is 
mentioned in the description of Hungarian Patent Specification No. 153,303 
without disclosing any reaction conditions. 
The most commonly used reactants are the isocyanates. These methods require 
the preparation of an isocyanate by reacting the amine and phosgene, 
potassium cyanate or dimethylsulphate, acetic anhydride and sodium azide, 
sodium acetamide and thionyl chloride, etc. 
There are several known methods for the preparation of methyl isocyanate or 
other isocyanates from phosgene and the corresponding amine. This reaction 
may be carried out by reacting the primary amine in vapor phase with 
phosgene and converting the carbamoyl chloride thus obtained into 
isocyanate by splitting off hydrochloric acid. 
A further known method comprises the reaction of potassium cyanate and 
dialkylsulphate [Schotta and Lorenz]; the yields amount to 50-55%. It is 
further reported that methylisocyanate may be prepared by the reaction of 
acetic anhydride and sodium azide [U.S. Pat. No. 2,544,709]. This reaction 
is however expensive and complicated, since acid halides or acid 
anhydrides are treated in a solvent with alkali azide or alkaline earth 
metal azide, at 0.degree.-45.degree. C the azide is decomposed with water 
and the isocyanate is subjected to fractional distillation. 
It is known furthermore that on reacting phosgene with primary amines or 
secondary amines the corresponding symmetrical urea derivatives are 
obtained in very good yields [H.W.8, pages 117, 120-123 and 154-157]. 
The safety measures ordered for the elimination of these reactions are 
partly due to the aforesaid. In every case, whenever phosgene is not used 
in a very large excess there is a possibility for the formation the diurea 
derivative and consequently the compounds can no more be converted into 
the isocyanate. 
Probably the above reactions are partly responsible for the fact that the 
yields of the published procedures are generally far below the desired 
value. 
The present invention is based on the surprising recognition that on 
introducing phosgene into a solution which contains an organic compound 
comprising a phenolic hydroxy group and a primary amine, the carbamate is 
produced in a single step. 
According to a preferred embodiment of our process the reactants (namely 
the phenol and amine components) and the phosgene in parallel are added to 
the reaction mixture containing the solvent. 
In order to achieve the desired results, it is essential to add an acid 
binding agent to the reaction mixture at a suitable point of time. The 
acid binding agent may be applied from the beginning of the reaction or at 
a later state of the addition of the reactants. 
One may proceed preferably by using alkali hydroxides, alkali carbonates or 
alkaline earth metal carbonates for this purpose. The said acid binding 
agents are preferably added continuously to the reaction mixture. 
According to a particularly preferred embodiment of our process, the acid 
binding agent is added so as to form as heterogenous phase which separates 
from the organic solvent layer. Organic acid binding agents or ammonium 
carbonate may be used as well. 
The acid binding agent may be added as a solid substance or as a solution 
(e.g. aqueous solution). 
As solvent preferably halogenated hydrocarbons (e.g. dichloroethane or 
dichlorobenzene) may be used. Water-immiscible organic solvents (e.g. 
toluene) may be used too. 
The process of the present invention is particularly suitable for the 
preparation of compounds of the formula 
##STR3## 
wherein R.sup.1 is alkyl, alkyl substituted by halogen, alkyl substituted 
by alkoxy, aryl, aryl substituted by halogen, aryl substituted by alkyl, 
aryl substituted by alkoxy, aralkyl, aralkyl substituted by halogen, 
aralkyl substituted by alkyl, aralkyl substituted by alkoxy, cycloalkyl 
substituted by halogen, cycloalkyl substituted by alkyl or cycloalkyl 
substituted by alkoxy, and 
R.sup.2 is an aromatic group, an aromatic group substituted by alkyl, an 
aromatic group substituted by halogen, an aromatic group substituted by 
alkoxy, a heteroaromatic group, a heteroaromatic group substituted by 
alkyl, a heteroaromatic group substituted by halogen, or a heteroaromatic 
group substituted by alkoxy, by the reaction of phosgene with a phenol of 
the formula: 
EQU R.sup.2 --OH 
and further by reaction of a primary amine of the formula: 
EQU R.sup.1 ---NH.sub.2 
the improvement by reacting all three of the abovementioned reactant 
solution in a common water-immiscible organic solvent in the same reaction 
vessel at the same time in the presence of an acid binding agent to yield 
the compound of formula 
##STR4## 
The process of the present invention provides a highly advantageous method 
for the preparation of alkyl-1-butyl-carbamoyl-benzimidazole-2-carbamates 
(1-n-butyl-carbamoyl-benzimidazole-2-carbaminic acid alkyl esters). 
Further details of the present invention are to be found in the Examples.

EXAMPLES: 
1. Into a 1 liter glass equipped with a stirrer, reflux condenser, 
thermometer gas introducing tube and a dropping funnel 150 ml of tolune 
are added, whereupon a solution of 46.5 g (0.5 moles) of aniline and 70 ml 
of toluene is added dropwise at 0.degree. C within an hour. In an other 
apparatus 80 g (0.48 moles) of 2-[1,3-dioxolane-2-yl]-1-hydroxy-benzene, 
35 ml of toluene and 10 ml of triethylamine are admixed under stirring, 
whereupon the toluene solution is poured into the second apparatus under 
constant introduction of phosgene. The temperature of the reaction mixture 
is raised to 90.degree.-92.degree. C and it is stirred for 2 hours, while 
phosgene is continuously led into the reaction mixture. Thereafter 
nitrogen is led into the apparatus at 80.degree. C for 2 hours. The 
reaction mixture is cooled to room temperature, stirred for 8 hours; the 
precipitated product is filtered off and washed successively with a small 
amounts of toluene and 60 ml of ethanol (0.degree. C). Thus 124.5 g of 
2-[1,3-dioxolane-2-yl]-phenyl-N-phenyl-carbamate are obtained. 
The compounds of the formula I enumerated in Table I are prepared in an 
analoguous manner to the process of the preceding examples by using the 
corresponding starting materials. 
______________________________________ 
##STR5## (I) 
M.P. 
EXAMPLE R.sup.1 R.sup.2 C .degree. 
2 CH.sub.3 
##STR6## 111-114 
##STR7## 
##STR8## 
4 
##STR9## 
##STR10## 182-185 
5 
##STR11## 
##STR12## 158-165 
6 
##STR13## 
##STR14## 171-179 
7 
##STR15## 
##STR16## 198-201 
8 CH.sub.3 
##STR17## 150-152 
9 CH.sub.3 
##STR18## 78-82 
10 CH.sub.3 
##STR19## 113-115 
11 CH.sub.3 
##STR20## 92-94 
______________________________________