Process for the preparation of N-alkyl-monosubstituted carbamic acid esters

A process for the preparation of N-alkyl-monosubstituted carbamic acid esters by reacting an unsubstituted carbamic acid ester and an aliphatic primary amine at a suitable pressure and reaction temperature in the presence of a monohydric aliphatic alcohol and preferably in the presence of a strongly basic tertiary amine as catalyst. Optionally an inert co-solvent in addition to the alcohol may be employed.

BACKGROUND OF THE INVENTION 
U.S. Pat. No. 3,161,676 describes a process for the preparation of a 
substituted urea by reacting a carbamic acid ester with a primary and 
sterically unhindered secondary aliphatic amines in the presence of a 
metal compound Lewis acid catalyst, such as cupric acetate. 
There is no known prior art which describes the preparation of 
N-alkyl-monosubstituted carbamic acid esters by reacting an unsubstituted 
carbamic acid ester and an aliphatic primary amine in the presence of a 
monohydric aliphatic alcohol with or without the use of a tertiary amine 
catalyst. 
Many important commercial applications have been developed for the carbamic 
acid ester products of this invention, for example, as herbicides, 
insecticides, medicinals and as chemical intermediates. 
SUMMARY OF THE INVENTION 
The present invention is based on the unexpected discovery that it is 
possible to produce, in high yield and high conversions of reactants, an 
N-alkyl-monosubstituted carbamate, such as ethyl-n-octylcarbamate, by the 
reaction of an aliphatic primary amine such as n-octyl-amine with an 
unsubstituted carbamate such as ethyl carbamate at a temperature of from 
about 125.degree. C. to 250.degree. C. in the presence of a monohydric 
aliphatic alcohol such as ethyl alcohol and preferably in the presence of 
a tertiary amine catalyst. While the alcohol employed may, among other 
things, function as a solvent to effect the reaction, a co-solvent in 
addition to the alcohol may alternatively be used in the process of the 
invention. 
It is a primary object of this invention therefore, to provide a novel 
process for the preparation of N-alkyl-monosubstituted carbamates. 
It is another object of this invention to provide a novel reaction system 
for the conversion of an unsubstituted carbamic acid ester and an 
aliphatic primary amine to N-alkyl-monosubstituted carbamic acid esters, 
such as ethyl-n-octyl carbamate. 
These and other objects and advantages of this invention will become 
apparent from the description of the invention which follows, and from the 
claims. 
DETAILED DESCRIPTION OF THE INVENTION 
In accordance with this invention an N-alkyl-monosubstituted carbamic acid 
ester is produced by reacting an unsubstituted carbamic acid ester of the 
general formula NH.sub.2 CO.sub.2 R wherein R is a straight or branched 
chain alkyl group containing from 1 to 18 carbon atoms, with a primary 
aliphatic amine of the general formula R'NH.sub.2 wherein R' is a straight 
or branched chain alkyl group containing from 1 to 18 carbon atoms, at a 
temperature in the range of from about 125.degree. C. to 250.degree. C. in 
the presence of a monohydric aliphatic alcohol having from 1 to 18 carbon 
atoms and preferably in the presence of a tertiary amine catalyst. 
Alternatively an inert solvent in addition to the alcohol may be employed. 
The R and R' may contain substituents which do not interfere with the 
reaction, such as alkoxy, sulfur, sulfoxide, sulfone, etc. radicals. 
The reaction between the unsubstituted carbamic acid ester and the 
aliphatic primary amine may be carried out in any suitable reactor, such 
as an autoclave, which is generally equipped with a means for agitation, 
means for regulating temperature and pressure and means for removing 
by-products ammonia, and possibly alcohol vapor. Although the order of 
addition of the reactants, alcohol and solvents and catalyst components, 
if any, may vary, a general procedure for carrying out the reaction is to 
charge the unsubstituted carbamic acid ester, primary aliphatic amine, 
alcohol and, preferably, a strongly basic tertiary amine catalyst into the 
reaction vessel and then heat the mixture to the desired temperature at 
atmospheric pressure or higher pressures, if required. The reaction can be 
carried out batchwise, semicontinuous, or as a continuous process. The 
reaction products are recovered and treated by any conventional method, 
such as distillation or fractionation to effect separation of the 
N-alkyl-monosubstituted carbamate from unreacted starting material, 
catalyst, solvent and by-products. 
The unsubstituted carbamic acid esters employed as reactants in the process 
of the present invention conform to the general formula NH.sub.2 CO.sub.2 
R wherein R is a substituted or unsubstituted straight or branched chain 
alkyl group containing from 1 to 18 carbon atoms. Representative 
unsubstituted carbamic acid esters suitable for use in this invention 
include, for example, methyl carbamate, ethyl carbamate, normal and 
isobutylcarbamates, propyl carbamate, amyl carbamate, isoamyl carbamate, 
hexyl carbamate, octyl carbamate, 2-ethylhexyl carbamate, decyl 
carbamates, heptyl carbamate, nonyl carbamate, 2 ethyl-1-butyl carbamate, 
3,5-dimethyl-1-hexyl carbamate, ethyl tert-butylcarbamate, propyl 
(5,5-dimethylhexyl) carbamate and the like. In general, the methyl and 
ethyl esters are more readily available and are, therefore, more 
preferred. 
The aliphatic primary amines employed as reactants in the process of the 
present invention conform to the general formula R'NH.sub.2 wherein R' is 
a straight or branched chain alkyl group containing from 1 to 18 carbon 
atoms. Representative aliphatic primary amines as hereinabove described 
include, for example, methylamine, ethylamine, n-propylamine, 
iso-propylamine, n-, iso-, sec-, and tert-butylamines, n-decylamine, 
n-dodecylamine, n-octylamine, n-tetradecylamine, allylamine, n-amylamine, 
and the like. 
The alcohols which are employed are monohydric aliphatic alcohols 
containing from 1 to 18 carbon atoms. It is generally preferred that the 
alcohol employed correspond to the alkyl group of the reactant 
unsubstituted carbamic acid ester in order to prevent the preparation of 
mixed N-alkyl-monosubstituted carbamates. The alcohols, in addition to 
acting as the reaction solvent, substantially inhibit side reactions and 
are generally employed in a molar excess based on the amine or 
unsubstituted carbamic acid ester reactants, i.e., from about a molar 
ratio of 0.5:1 to 15:1 of alcohol to amine or carbamate reactant employed 
to produce the N-alkyl-substituted carbamic acid esters. Representative 
alcohols which may be employed in the process of this invention include, 
for example, methanol, ethanol, n-propanol, n- and iso-butyl alcohols, 
amyl alcohol, hexanol, heptanol, octanol, nonanol, decanol, n-dodecanol, 
n-pentadecanol, as well as cetyl alcohol, stearyl alcohol and myristyl 
alcohol, 2-ethylhexanol, 2-methyl pentanol, 2-ethyl-1-butanol, 
3,5-dimethyl-1-hexanol, and the like. The lower aliphatic alcohols having 
1 to 4 carbon atoms are preferred. 
A general postulated equation for the reaction of the present invention may 
be represented as follows: 
##STR1## 
wherein R and R' are as hereinabove described. A wide variety of 
N-alkyl-monosubstituted carbamates can be prepared by the process of this 
invention. 
Although an optional feature of this invention, it has been discovered that 
improved yields and increased reaction rates can be obtained when the 
above reaction is carried out in the presence of a strongly basic tertiary 
amine catalyst. The tertiary amine catalysts, may be an aliphatic, 
cycloaliphatic, araliphatic or aromatic amine containing from 1 to 18 
carbon atoms, which may be interrupted by oxygen, sulfur, nitrogen, 
sulfoxide or carbonyl substituents. In general, the amine employed as 
catalyst should be easily separated from reaction product and by-products. 
Representative amines suitable for use in the process of the invention 
include, for example, the trialkylamines such as the trimethyl, triethyl, 
tripropyl, tributyl, trihexyl, trioctyl, tridecyl, tridodecyl, etc. 
amines, triphenylamine, n-dodecyldimethylamine, 
n-tetradecyldimethylamnine, n-hexyldecyldimethylamine, 
n-octyldecyldimethylamine, N,N,N',N'-tetramethylethylenediamine, 
N,N-dioctyl-1-octylamine, 1,4-diazabicyclo[2.2.2]octane, 
4(N,N-dimethylamino) pyridine, pyridine, 1,5-diazabicyclo[3.4.0]non-5-ene, 
1,8-diazabicyclo[5.4.0]-undec-7-ene, 1,1,3,3-tetramethylbutylamine, 
methyldiethylamine, butyldimethylamine, benzyldimethylamine, and the like. 
The amount of tertiary amine catalyst which can be used in the process 
will generally range between about 0.01 to 35 mole percent, preferably 0.1 
to 20 mole percent based on the aliphatic primary amine employed in the 
reaction, but greater or lesser quantities may be used if desired. 
Although the process of the invention is preferably carried out using the 
monohydric aliphatic alcohol as the reaction solvent, other solvents or 
mixtures of solvents which are stable and substantially chemically inert 
to the components of the reaction system may be employed as a co-solvent 
in the reaction system if desired. Suitable co-solvents which may be 
employed, and generally in amounts of from 0 to 50 weight percent based on 
the reaction mixture, include, for example, benzene, toluenes, xylenes, 
dichlorobenzene, tetrahydrofuran, 1,2-dimethoxyethane, diphenylether, 
nitrobenzene, diethyleneglycol dimethyl ether, triethyleneglycol dimethyl 
ether, dimethylsulfoxide, and the like. 
The ratio of reactants, i.e., unsubstituted carbamic acid ester and 
aliphatic primary amine may be varied over any convenient range. The mole 
ratio of amine to unsubstituted carbamate may be between about 10:1 to 
0.1:1 and is preferably between about 5:1 to 0.25:1. 
The reaction of the present invention will proceed at temperatures of from 
about 125.degree. C. to 250.degree. C. It is generally preferred to 
operate the process at temperatures of from about 175.degree. C. to 
225.degree. C. to obtain a convenient rate of reaction. The reaction 
temperature will depend on the particular N-alkyl-monosubstituted carbamic 
acid ester being produced and should be below the temperature at which 
significant decomposition of the product ester might occur. 
The process of the present invention is generally carried out at 
atmospheric pressure or the autogenous pressure of the reaction system, 
although higher pressure of up to 50 atmospheres may be used an especially 
at the higher reaction temperatures or when the reaction temperature is 
above the boiling point of the alcohol and/or reactant amine. 
Subatmospheric pressures may be employed, if desired. 
Ammonia resulting from the reaction must be removed during the course of 
the reaction, otherwise reduced yields of product carbamate are obtained. 
When the reaction is carried out at one atmosphere the ammonia is simply 
allowed to escape from the reaction vessel. In reactions where elevated 
pressures are employed provisions must be made to remove ammonia. A 
simple, convenient method is to strip the ammonia from the reactor with a 
dry inert gas, such as nitrogen and/or with the resulting alcohol vapor, 
provided the alcohol employed is volatile at the reaction temperature. 
When the alcohol vapor is used to strip or aid in stripping the ammonia 
from the reactor, additional or makeup alcohol can be added to the reactor 
at a rate to compensate for the vapor loss. 
The reaction time is generally dependent on the N-alkyl-monosubstituted 
carbamate being produced, the reaction temperature and the catalyst 
employed, if any, and will vary depending on whether the process is 
continuous or batch but will generally range between about one to several 
hours.

The following Examples are provided to illustrate the invention in 
accordance with the principles of this invention, but are not to be 
construed as limiting the invention in any way except as indicated by the 
appended claims. 
In the Examples which follow, the reactions were run in a 300 ml stainless 
steel stirred autoclave. The amine, unsubstituted carbamic acid ester and 
alcohol, along with tertiary amine catalyst and co-solvent, if any, are 
charged to the reactor which is then flushed with nitrogen and the reactor 
heated to the desired reaction temperature for a specified time period. 
During the reaction vaporized alcohol and product ammonia are stripped 
from the reactor with or without the aid of an inert gas. Makeup alcohol 
is pumped into the reactor at a rate closely approximating the alcohol 
removed. At the end of the reaction time, the autoclave is cooled to 
ambient temperature and the contents combined with the stripped alcohol 
which was collected in a dry ice cooled trap and the total mixture 
analyzed by liquid chromatography (LC) for conversion of amine and 
unsubstituted carbamic acid ester and selectivities to 
N-alkyl-monosubstituted carbamate. Amine and the unsubstituted carbamate 
conversions were calculated on the basis of moles of the amine and 
carbamate consumed by the reaction. Product selectivities were based on 
the moles of amine or unsubstituted carbamate consumed in preparing the 
N-alkyl-monosubstituted carbamate and by-products. 
EXAMPLE 1 
0.5 mole n-octylamine, 0.5 mole ethyl carbamate, 2.67 moles of dry ethanol 
(200 proof) and 0.26 mole of triethyleamine catalyst was charged to the 
autoclave which was flushed several times with nitrogen and heated to 
200.degree. C. for a period of 3 hours under the autogenous pressure of 
reaction. During the reaction period ethanol and ammonia were stripped 
from the reactor with nitrogen at an average of 1.7 ml of ethanol per 
minute. The ethanol vapor containing ammonia and a small amount of 
n-octylamine was condensed in a dry ice cooled trap. Makeup ethanol was 
pumped into the autoclave at a rate closely approximating the amount 
stripped. After the reaction period, the autoclave was cooled and the 
contents along with the ethanol condensate analyzed. LC analysis showed an 
amine conversion of 100 percent and an ethylcarbamate conversion of 83 
percent with selectivities to ethylphenylcarbamate of 66 mole percent and 
80 mole percent based on the amine and ethylcarbamate, respectively. 
EXAMPLES 2 to 9 
In Examples 2 to 9, which follow in Table form, the general procedure of 
Example 1 and as hereinabove described was repeated using various amines, 
unsubstituted carbamic acid esters, alcohols, tertiary amine catalysts and 
conditions as shown in Table 1. The results based on amine and 
unsubstituted carbamates conversion as well as the selectivities to the 
N-alkyl-monosubstituted carbamate are set forth in Table 2. 
TABLE 1 
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Charge (Moles) 
Unsubstituted 
Example 
Amine Carbamate 
Alcohol 
Catalyst 
Conditions 
No. (moles) (moles) (moles) 
(moles) 
Temperature .degree.C. 
Time 
__________________________________________________________________________ 
2.sup.1 
n-octylamine 
ethylcarbamate 
ethanol 
DBU.sup.2 
175 3 hrs. 
(.5) (.5) (2.57) 
(.005) 
3 n-octylamine 
ethylcarbamate 
ethanol 
pyridine 
200 3 hrs. 
(.5) (.5) (2.57) 
(.10) 
4 n-octylamine 
methylcarbamate 
methanol 
DBN.sup.3 
200 2 hrs. 
(.5) (.5) (2.57) 
(.01) 
5 n-dodecylamine 
octylcarbamate 
octanol 
TEA.sup.4 
175 3 hrs. 
(.5) (1.0) (2.57) 
(.26) 
6 n-dodecylamine 
ethylcarbamate 
ethanol 
TOA.sup.5 
200 3 hrs. 
(.5) (1.5) (2.0) 
(.20) 
7 n-octylamine 
decylcarbamate 
decanol 
DBU 200 1 hr. 
(.5) (.5) (3.0) 
(.02) 
8 ethylamine 
ethylcarbamate 
ethanol 
TEA 200 3 hrs. 
(.5) (.5) (2.67) 
(.26) 
9 n-octylamine 
ethylcarbamate 
ethanol 
none 200 3 hrs. 
(.5) (.5) (2.57) 
__________________________________________________________________________ 
.sup.1 100 ml benzene added as cosolvent 
.sup.2 1,8Diazabicyclo[5.4.0]undec7-ene 
.sup.3 1,5Diazabicyclo[4.3.0]non5-ene 
.sup.4 triethylamine 
.sup.5 trinoctylamine 
TABLE 2 
______________________________________ 
Amine Unsubstituted Carbamate 
Mole % Mole % 
Example Mole % Carbamate Mole % Carbamate 
No. Conversion 
Selectivity 
Conversion 
Selectivity 
______________________________________ 
2 100 EOC.sup.1 31 
69 EOC 45 
3 100 EOC 75 80 EOC 87 
4 100 MOC.sup.2 58 
70 MOC 71 
5 100 ODDC.sup.3 25 
30 ODDC 42 
6 100 EDDC.sup.4 70 
25 EDDC 93 
7 88 DOC.sup.5 30 
45 DOC 53 
8 100 EEC.sup.6 71 
76 EEC 82 
9 80 EOC 20 55 EOC 29 
______________________________________ 
.sup.1 EOC Ethyl Noctylcarbamate 
.sup.2 MOC Methyl Noctylcarbamate 
.sup.3 ODDC Octyl Ndodecylcarbamate 
.sup.4 EDDC Ethyl Ndodecylcarbamate 
.sup.5 DOC Decyl Noctylcarbamate 
.sup.6 EEC Ethyl Nethylcarbamate