Process for the preparation of aromatic urethanes

A process for the preparation of aromatic urethanes by reacting an aromatic amine, an alcohol and carbon monoxide in the presence of a catalytic quantity of a copper salt, oxygen and a dehydrating agent is disclosed. The reaction is preferably carried out using a copper halide catalyst and dehydrating agents which combine with water to release the alcohol used in the preparation of the urethane product.

BACKGROUND OF THE INVENTION 
This invention relates to the preparation of urethanes and, more 
particularly, to the preparation of aromatic urethanes by reaction between 
aromatic amines, alcohols, and carbon monoxide. 
Aromatic urethanes have many important industrial and medical uses, 
including the preparation of drugs, such as tranquilizers and muscle 
relaxants, the production of herbicides and insecticides, and the 
preparation of isocyanates, important building blocks for the production 
of polyurethanes. 
Increasing interest in aromatic urethanes has led to investigations for 
more economical and efficient processes for their production. Recent 
research has been directed to the preparation of urethanes by the 
carbonylation reaction between amines, alcohols, and carbon monoxide using 
various metal catalysts. Unfortunately, these reactions have been 
generally catalyzed by expensive Group VIII noble metal catalysts, such as 
the salts of palladium and platinum. Some success has been observed in the 
oxidative carbonylation of aliphatic and heterocyclic amines to urethanes 
with carbon monoxide and alcohols using relatively inexpensive copper 
salts. 
Netherlands Patent No. 94,613 discloses the preparation of urethanes by 
reacting amines, alcohols and carbon monoxide using copper compound 
catalysts. Although this patent recommends that the reaction be carried 
out in the absence of water, there is no teaching of the use of water 
removal means. Other publications suggest that the presence of water 
favors carbamate production in this reaction. For example, West German 
Patent No. 1,105,866 which discloses the preparation of urea compounds by 
the carbonylation of amines with carbon monoxide using copper compounds, 
states that drying agents can be added to the reaction mixture to 
substantially eliminate the production of carbamates. 
Since carbon monoxide is a very inexpensive starting material and copper 
salts are relatively inexpensive catalysts, the preparation of aromatic 
urethanes from amines, alcohols and carbon monoxide using copper salt 
catalysts is potentially of considerable economic importance. Accordingly, 
it would be desirable to adapt this procedure to the preparation of 
aromatic urethanes from aromatic amines. 
SUMMARY OF THE INVENTION 
The above-described process has been improved by this invention so that 
aromatic urethanes can now be prepared by the reaction between aromatic 
amines, alcohols and carbon monoxide using copper salts as catalysts. 
Accordingly, it is an object of the invention to present an improved 
method for the preparation of aromatic urethanes. It is another object of 
the invention to present a method for preparing aromatic urethanes by the 
reaction of carbon monoxide, aromatic amines and alcohols. It is another 
object of the invention to present a method of preparing aromatic 
urethanes using copper salts as catalysts. It is another object of the 
invention to present a method for producing aromatic urethanes in high 
yields by the reaction of aromatic amines, alcohols and carbon monoxide 
using copper salt catalysts. It is another object of the invention to 
present a method of preparing aromatic urethanes from aromatic amines, 
alcohols and carbon monoxide using a regenerating copper catalyst system. 
These and other objects of the invention will become more obvious from the 
following description and examples. 
The above objects are achieved by reacting aromatic amines, alcohols and 
carbon monoxide using a copper salt catalyst in the presence of a small 
amount of oxygen or an oxygen-containing gas mixture and employing means 
for water removal, such as incorporating dehydrating agents into the 
reaction mixture. The reaction is generally carried out at a temperature 
in the range of about 60.degree. to 300.degree. C. and a pressure of about 
1 to 700 atmospheres. In preferred embodiments the copper salt is a copper 
halide, the reaction zone temperature is in the range of about 100.degree. 
to 250.degree. C., the reaction zone pressure is in the range of about 50 
to 150 atmospheres, dehydrating agents which release the alcohol used as a 
reactant are used, and the amount of oxygen present in the reaction zone 
is less than the lower limit of the explosive range of mixtures of oxygen 
and carbon monoxide. 
DESCRIPTION OF THE INVENTION 
The carbonylation reaction of the invention may be carried out in any high 
pressure batch-type or continuous reactor. A general procedure is to 
charge the amine, alcohol, dehydrating agent, catalyst, and the oxygen or 
oxygen-containing gas mixture into the reaction vessel, introduce the 
proper amount of carbon monoxide gas to obtain the desired reaction 
pressure and then heat the mixture to and maintain it at the desired 
temperature for the appropriate period. The reaction can be carried out 
batchwise or as a continuous process and the order of addition of the 
reactants to the reaction vessel may be varied as desired. The reaction 
products can be conveniently recovered and treated by any conventional 
method, such as filtration, distillation, etc. to effect separation of the 
aromatic urethane from unreacted materials, catalyst, by-products, etc. 
Any monofunctional or polyfunctional primary, secondary or tertiary 
aromatic amine or mixture of amines may be used in the process of the 
invention. The amine reactant has the structural formula 
EQU R(NR.sub.1 R.sub.2).sub.n 
wherein R is a carbocyclic aromatic group comprised of 1 to 3 condensed or 
non-condensed rings, R.sub.1 and R.sub.2 may be the same or different and 
either or both may be hydrogen, a saturated or unsaturated aliphatic 
organic group containing up to 30 carbon atoms or a carbocyclic aromatic 
group comprised of 1 to 3 condensed or non-condensed rings, and n is at 
least 1. 
R may be unsubstituted or substituted with one or more alkyl groups 
containing up to 12 carbon atoms each, or other substituents such as 
halide, hydroxy, ether, ester, mercaptan, thioether, thioester, amino, 
amido, nitro or nitroso, etc., substituents or organic groups containing 
these substituents. 
When R.sub.1 and R.sub.2 are aliphatic organic groups, they can be 
hydrocarbons or can contain one or more of the substituents enumerated 
above as being optionally present in R. When they are not aromatic they 
are preferably hydrogen or alkyl groups having up to 12 carbon atoms. When 
R.sub.1 or R.sub.2 are aromatic groups they can be any of the groups 
mentioned in defining R and may be the same as or different from R. 
When n is 1 the amine is monofunctional and when n is greater than 1 the 
amine is polyfunctional. Preferred amines are those in which n is 1 to 3. 
If it is desired, a mixture of two or more aromatic amines may be used as 
the amine reactant. Also, the reaction mixture can contain one or more 
aliphatic or heterocyclic amines in addition to the aromatic amine 
reactant. 
Representative aromatic amines include aniline, diphenyl amine, triphenyl 
amine, N-methylaniline, N,N-dimethylaniline, N-methyl-N-ethylaniline, the 
toluidines, N-methyl-o-toluidine, N,N-dimethyl-p-toluidine, etc., the 
xylidines, N-methyl-N-ethyl-xylidine, N-methyl-p-hexylaniline, 
N-heptyl-m-pentylaniline, chloroaniline, N-methyl-p-bromoaniline, 
nitroaniline, nitrosoaniline, cyanoaniline, methoxyaniline, 
N-pentyl-o-nitroaniline, p-hydroxyethylaniline, 
N,N-dimethyl-m-mercaptopropylaniline, the phenylene diamines, the toluene 
diamines, N, N-diphenylamine, N-propyl-N-toluidinylaniline, 
4,4'-diaminodiphenylmethane, .alpha.-naphthylamine, .beta.-naphthylamine, 
1,5-diaminonaphthene, etc. The preferred aromatic amines are the 
mononuclear aromatic amines, such as aniline, N-methylaniline, 
N,N-dimethylaniline, phenylamine diamine, etc. 
The alcohol component used in the process of the invention has the 
structural formula 
EQU R(OH).sub.n 
wherein R is a mono- or polyfunctional aliphatic aromatic or cycloaliphatic 
organic group usually having 1 to 20 carbon atoms, and n is at least 1. 
When R is aliphatic or cycloaliphatic it preferably has 1 to 12 and most 
preferably 1 to 8 carbon atoms. When R is aromatic it is usually comprised 
of 1 to 3 condensed or non-condensed rings and is preferably comprised of 
one aromatic ring. R can be unsubstituted, i.e., a hydrocarbon group, or 
it can contain atoms other than hydrogen or carbon in its main chain or in 
groups pendent from the main chain. These substituents do not 
substantially interfere with the reaction of the invention. Typical 
substitutents present in alcohols useful in the invention include halogen 
atoms and ether, ester, amino, amido, cyano, nitro, nitroso, mercapto, 
thioester carboxy, alkoxy, etc., groups. When n is 1 the alcohol is 
monofunctional and when n is greater than 1 the alcohol is polyfunctional. 
In preferred embodiments n varies from 1 to 6 and most preferably from 1 
to 3. 
Representative alcohols within the scope of the above description include 
methanol, ethanol, n-, iso-, sec-and tert-butanol, amyl alcohol, hexanol, 
lauryl alcohol, cetyl alcohol, allyl alcohol, oleyl alcohol, 
3-chloroheptanol, ethoxyethanol, cyclohexanol, methylcyclohexanol, 
cyclohexanol, phenol, benzyl alcohol, chlorobenzyl alcohol, cresol, 
o-nitrobenzyl alcohol, p-aminophenol, anisyl alcohol, .beta.-naphthol, 
1,4-butanediol, ethylene glycol, 1,3-propanediol, 1,4-cyclohexanediol, 
etc. The preferred alcohols are the mono and difunctional saturated 
aliphatic or cycloaliphatic alcohols containing up to 8 carbon atoms, such 
as methanol, ethanol, butanol, cyclohexanol, and ethylene glycol and 
aromatic alcohols comprised of one aromatic ring, such as benzyl alcohol, 
phenol, and 2,4-toluenediol. 
The equivalents ratio of total aromatic amine to alcohol is not critical, 
but is usually about 0.8:1 to 2.2:1 and preferably about 0.9:1 to 1.1:1. 
The copper salts usable as catalysts in the process of the invention 
include copper(I) and copper(II) salts and mixtures of these. In general, 
any copper salt usable as a catalyst can be used in the invention. The 
copper salt anions may be inorganic, such as the halides, sulfates, 
sulfites, nitrates, nitrites, carbonates, etc.; or organic, such as acyl 
groups, including acetate, formate, propionate, alkoxides such as 
methoxide, ethoxide, etc. 
Examples of representative copper salts are copper(I) chloride, copper(II) 
chloride, copper(I) bromide, copper(II) bromide, copper(II) iodide, 
copper(II) formate, copper(II) acetate, copper(I) propionate, copper(II) 
methoxide, copper(I) ethoxide, etc. The preferred copper salts are the 
halides, particularly the copper(II) halides, such as copper(II) chloride 
and copper(II) bromide. 
The amount of catalyst used in the reaction may vary from the minimum 
amount which is catalytically effective up to about 15%, based on the 
total weight of aromatic amine present in the reaction zone. Amounts 
greater than about 15% can be used, if desired, however, the efficiency of 
the reaction decreases as larger amounts of catalyst are employed. The 
amount of copper salt catalyst usually used in the process of the 
invention varies from about 0.01 to about 15%, and preferably from about 
0.1 to about 5%, based on the total weight of aromatic amine present in 
the reaction zone. 
A ligand or coordination complex compound of the metal catalyst can be 
included, if desired, in the catalyst formulation to modify the properties 
of the copper salt catalyst. Examples of suitable compounds include 
organic ligands, such as alkyl or aryl phosphines or phosphine oxides, 
arsines or stibines, heterocyclic amines such as pyridine, and inorganic 
ligands, such as tin chloride, etc. When these agents are included they 
are often used in amounts up to about four molar equivalents of ligand per 
mole of copper. 
The reaction is carried out in the presence of a catalyst oxidizing agent. 
During the reaction between the carbon monoxide and the aromatic amine, 
the copper(II) ions are reduced to copper(I) ions. The oxidizing agent 
functions to oxidize the copper(I) back to the copper(II) state. It is not 
known what additional part the oxidizing agent plays in he process of the 
invention, but it has been discovered that aromatic amines will not react 
with carbon monoxide to produce aromatic formamides in the absence of an 
oxidizing agent, such as oxygen. Suitable oxidizing agents include oxygen 
or other suitable oxidizing agents, such as quinone. When oxygen is used 
it may be introduced as pure oxygen or as a component in a gas mixture, 
such as air. The amount of oxygen present in the reaction zone at any 
given time is preferably such that the concentration of oxygen is less 
than 6.1 volume percent. This is the lower limit of the explosive range of 
oxygen in carbon monoxide as determined from the tables on pages 1771-1772 
of the Handbook of Chemistry and Physics, 37th Edition, 1955. Although the 
reaction can be carried out at oxygen levels of 6.1 volume percent or 
greater, it is preferred to keep the oxygen and carbon monoxide levels at 
safe concentrations to avoid the hazard of an explosion. 
During the course of the reaction between the aromatic amine, alcohol and 
carbon monoxide, the reoxidation of copper(I) to copper(II) produces water 
as a by-product. Although water can usually be tolerated when aliphatic 
urethanes are prepared by the reaction used in this invention, it has been 
discovered that aromatic amines will not react with alcohols and carbon 
monoxide to produce aromatic urethanes unless the reaction is carried out 
under conditions such that the water formed during the reaction process is 
removed from the reaction zone. In the present invention this is 
accomplished by process techniques, such as azeotropic distillation or by 
carrying out the reaction in the presence of dehydrating agents. When 
azeotropic distillation is employed the water can be removed with a 
portion of the alcohol or other solvent. Suitable azeotropic mixtures are 
those formed between alcohols and water. It is preferable to use 
dehydrating agents in the process of the invention. Especially preferred 
dehydrating agents are those which react chemically with water to release 
alcohols as exemplified by the following reactions: 
##STR1## 
Suitable dehydrating agents include orthoesters, ketals, acetals, 
enolethers, trialkylorthoborates. Preferred dehydrating agents are those 
which will release lower alcohols, i.e., aliphatic or cycloaliphatic 
alcohols having up to 8 carbon atoms in their structures, upon reaction 
with water. Particularly suitable dehydrating agents are those which, upon 
contact with water, release the particular alcohol from which the 
urethanes is being prepared. Examples of preferred dehydrating agents are 
trimethylorthoformate, triethylorthoformate, tributylorthoformate, 
2,2-dimethoxypropane, 2,2-di-n-butoxypropane, 1,1-dimethoxycyclohexane, 
1,1-di-n-butoxycyclohexane, 1,1-dimethoxymethane, 1,1-diethoxyethane, 
1-methoxyethane, 2-ethoxyprop-2-ene, 1-methoxycyclohex-1-ene, 
trimethylborate. The most preferred dehydrating agents are the orthoesters 
and ketals which react with water to release alcohols having up to 6 
carbon atoms in their structures. It is most preferred that the alcohol 
being released be the alcohol which is used as the reactant. 
The reaction can be carried out with or without a solvent. However, it is 
preferred to use a solvent. When lower molecular weight amines and excess 
alcohol are reacted there is no need for additional solvents. However, in 
some cases, for example when higher molecular weight reactants are used, 
it may be desirable to conduct the reaction in the presence of a solvent. 
Preferred solvents are the non-oxidizable polar solvents, such as methyl 
acetate, chlorobenzene, etc. It is usually preferred to use a sufficient 
quantity of solvent to completely dissolve the reactants and to prevent 
locallized overheating. The optimum amounts for each reaction system can 
be easily determined.

The following examples illustrate specific embodiments of the invention. 
Unless otherwise indicated parts and percentages are on a weight basis. 
EXAMPLE I 
A solution of 23.28 g (250 mmole), aniline, 53.06 g (500 mmole) 
trimethylorthoformate, and 60.00 g of absolute methanol was charged into 
the autoclave along with 3.36 g (25 mmole) anhydrous copper(II) chloride. 
The autoclave is sealed and charged with carbon monoxide to a pressure of 
1600 psig. The temperature in the autoclave is raised to and maintained at 
125.degree. C. The reaction is initiated by charging oxygen into the 
autoclave until the pressure reaches 1700 psig. The gas charge line is 
then flushed by charging carbon monoxide into the reactor until the 
autoclave pressure reaches 1800 psig. A considerable pressure drop is 
observed over the course of the 2 hour reaction period. GLC (gas-liquid 
chromatography) and ALC (analytical liquid chromatograph) analyses 
indicate that 29.54 g (195.6 mmole) of methyl-N-phenylcarbamate is formed. 
Based on aniline as a limiting reactant, a selectivity of 81.6 mole % to 
methyl-N-phenylcarbamate at 95.9% aniline conversion is obtained. 
EXAMPLE II 
The procedure of Example I is repeated except that no trimethylorthoformate 
is employed. No pressure drop is observed over the course of a four hour 
residence period. GLC and ALC analyses indicate that no 
methyl-N-phenylcarbamate is formed. Most of the aniline initially charged 
is recovered unchanged. 
EXAMPLE III 
The procedure of Example I is repeated except that 26.75 g (250 mmole) 
N-methylaniline is substituted for the aniline. A pressure drop of 1580 
psi over the course of a two hour period is observed. GLC and ALC analyses 
indicate the presence of 27.62 g (167.4 mmole) of 
methyl-N-methyl-N-phenylcarbamate. Based on N-methylaniline as a limiting 
reagent, a selectivity of 72 mole % to methyl-N-methyl-N-phenylcarbamate 
at 93% N-methylaniline conversion is obtained. 
EXAMPLE IV 
The procedure of Example I is repeated except that 24.75 g (125 mmole) of 
4,4'-diaminodiphenylmethane is substituted for the aniline and 1.68 g 
(12.5 mmole) anhydrous copper(II) chloride is used. a strong exotherm and 
a rapid pressure drop of about 1475 psi over the course of a two hour 
resistance period is observed. GLC and ALC analyses indicate that 31.03 g 
(98.8 mmole) of diphenylmethane-4,4'-bis(methylurethane)(MDIU) is formed. 
Based on 4,4'-diaminodiphenylmethane as a limiting reagent, a selectivity 
of 85 mole % to MDIU at 93% diaminodiphenylmethane conversion is obtained. 
EXAMPLE V 
The procedure of Example I is repeated except that benzyl alcohol is 
substituted for the methanol and tribenzylorothoformate is substituted for 
the trimethylorthoformate. GLC and ALC analyses will indicate the 
formation of substantial amounts of benzyl-N-phenylcarbamate. 
EXAMPLE VI 
The procedure of Example I is repeated except that 15.25 g (125 mmole) of 
2,4-diaminotoluene is substituted for the aniline and a mixture of 4.12 g 
(25 mmole) anhydrous copper(II) sulfate and 1.68 g (12.5 mmole) of 
copper(II) chloride is used as the catalyst. A pressure drop of 1275 psi 
over the course of a two hour period is observed. GLC and ALC analyses 
indicate the pressure of 18.41 g (77.3 mmole) of 
toluene-2,4-bis(methylcarbamate) (TDIU). Based on 2,4-diaminotoluene as a 
limiting reagent, a selectivity of 68 mole % of TDIU at 91% 
2,4-diaminotoluene conversion is obtained. 
EXAMPLE VII 
The procedure of Example I is repeated except that 35.79 g (250 mmole) 
2-naphthylamine is substituted for the aniline and 4.12 g (25 mmole) 
anhydrous copper(II) sulfate and 0.55 g (2.8 mmole) anhydrous copper(I) 
iodide is substituted for the copper(I) chloride. GLC and ALC analyses 
will indicate the presence of substantial amounts of 
methyl-N-(2-naphthyl)urethane. 
EXAMPLE VIII 
The procedure of Example I is repeated except that p-chloroaniline is 
substituted for the aniline, cyclohexanol is substituted for the methanol 
and 2,2-tricyclohexylpropane is substituted for trimethylorthoformate, GLC 
and ALC analyses will indicte the presence of substantial amounts of 
cyclohexyl-N-p-chlorophenylurethane. 
Although the invention has been described with particular reference to 
specific examples, it is understood that the scope of the invention is not 
limited thereto but is only determined by the breadth of the appended 
claims.