The present invention concerns a process for the preparation of compounds of the general formula I 
in which HETN signifies an aromatic aza-heterocycle with, in all, 5 or 6 ring atoms, whereby up to 3 ring atoms are nitrogen atoms, whereby up to two further aromatic carbon ring atoms can be condensed on the heterocycle and R signifies a straight-chained or branched alkyl group with 1 to 10 C-atoms, a benzyl group unsubstituted or substituted with up to three C1-4 alkyl groups, C1-4 alkoxy groups, halogen atoms, with a cyano group, a nitro group, a trifluoromethyl group or an alkoxycarbonyl group with up to 4 C-atoms, an aralkyl group or an alkenyl group. The term aralkyl group includes a lower alkyl radical with 2 to 10 C-atoms, wherein up to two H atoms are replaced by phenyl groups, which possibly in turn can be substituted with C1-4 alkyl group, a C1-4 alkoxy group, a cyano group, nitro group, a trifluoromethyl group, an alkoxycarbonyl group with up to 4 C-atoms or with up to three halogen atoms. The term alkenyl characterises an unsaturated hydrocarbon radical with up to 5 C-atoms.
Carbamates play a large part in many fields of chemistry, i.e. in the synthesis of medicaments (B. J. Ludwig, L. S. Powell, F. M. Berger, J. Med. Chem. 12, 462, 1969) or of plant protection agents (E. Bocker, W. Draber in: R. Wegler, Chemie der Pflanzenschutz und Schxc3xa4dlingsbekxc3xa4mpfungsmittel, Vol. 1, P. 220, Springer, Berlin, Heidelberg, New York 1970; Ullmann""s Encyclopedia of Industrial Chemistry, 5th ed., Vol. A5, p. 51, VCH Verlagsgesellschaft mbH, 1986).
Since some carbamide esters, depending upon the ester radical, can again be split by special reagents, their synthesis, also in protective group chemistry, is an important process for the reversible blocking of amine functions, especially in heterocycle chemistry and in peptide chemistry (P. J. Kocienski, Protecting Groups, THIEME Verlag Stuttgart, 1994; Theodora W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis, John Wiley and Sons, New York, 1991).
Open-chained carbamic acid esters can also be prepared by many processes (U. Petersen in HOUBEN-WEYL, Methoden der Organischen Chemie, Volume E4, Kohlensxc3xa4ure Derivate, p. 149 ff, Georg Thieme Verlag, Stuttgart, New York 1983). A frequently used method in the case of the protection of aza-heterocycles consists in the conversion of the aromatic NH group of the aza-heterocycle with the help of a chloroformic acid ester of the general formula I (scheme 1): 
Thus, in the case of the preparation of indole-N-carboxylic acid from indole and carbon dioxide (D. L. Boger, J. Org. Chem. 52, 3934, 1987) or of indole-N-carbamates from indole and chloroformic acid esters (A. C. Weedon, B. Zhang, Synthesis 1992, 95; E. Reimann, T. Hassler, H. Letter, Arch. Pharm. 323, 255, 1990), as base there is frequently used hydrolysis sensitive butyl lithium, dissolved in an inert solvent or, however, there find use quite special processes, such as e.g. phase transfer-catalysed reactions (A. C. Weedon, B. Zhang, Synthesis 1992, 95; E. Reimann, T. Hassler, H. Letter, Arch. Pharm. 323, 255, 1990).
Stimulated by the work of Ken J. Butcher for the preparation of carbamate esters from amines and carbon dioxide (Ken J. Butcher, Synlett 1994, 825), we investigated whether aza-heterocycles of the general formula II can be converted into heterocyclic carbamate esters of the general formula I (scheme 2) with use of carbon dioxide, alkali metal carbonate, especially caesium carbonate, and alkyl or arylhalides of the general formula III
HETN-Hxe2x80x83xe2x80x83II
R-HALxe2x80x83xe2x80x83III
whereby HETN and R possess the above-mentioned meaning and HAL stands for chlorine, bromine or iodine: 
Since the above-mentioned aza-heterocycles of the general formula II are, because of their physical and chemical properties, set to be counted with the classical amines and, as a rule, are more strongly acidic in comparison with the amines used by Ken J. Butcher, such as e.g. piperidine, benzylamine, N-methylbenzylamine and aniline, it was not to be expected that, in the case of carrying out of the reaction according to scheme 2 with use of azaheterocycles of the general formula II, heterocyclic carbamate esters of the general formula I would result. If one carries out the reaction as described by Ken J. Butcher with use of indole, caesium carbonate and benzyl bromide, then one finds only traces of the desired product, N-benzyloxycarbonylindole.
Surprisingly, however, it was found that carbamate esters of the general formula I can, nevertheless, be prepared under very mild and preparatively very simple conditions when one increases the amounts of the alkali metal carbonate used, especially caesium carbonate (2 to 4 equivalents, referred to the aza-heterocycle) and the amounts of alkyl or aryl halide (1.2 to 2 equivalents, referred to the aza-heterocycle) and, above all, prolongs the reaction time of 24 hours to 48 to 72 hours.
The preparative procedure is very simple and takes place as follows:
The aza-heterocycle and a 2 to 4 fold molar excess of alkali metal carbonate, especially caesium carbonate, are placed in a suitable dipolar aprotic solvent, such as e.g. dimethylformamide, acetonitrile, dimethylacetamide or N-methylpyrrolidone, at room temperature. With good stirring, carbon dioxide gas is now passed into the reaction mixture at room temperature with exclusion of moisture for 4 to 6 hours. The carbon dioxide gas stream is hereby produced by allowing dry ice to evaporate at room temperature which is present in an Erlenmeyer flask which is connected with the reaction vessel via a gas inlet pipe. One now adds to the reaction mixture in one portion the alkyl or aryl halide of the general formula III in question dissolved in a little solvent, passes in further carbon dioxide for 1 to 2 hours, again adds thereto about 10% to 100%, preferably 30% of the original amount of alkyl or aryl halide and then closes the reaction vessel. With closed reaction vessel, one now further stirs for 24 hours to 4 days, preferably 3 days, at room temperature. Thereafter, one pours the reaction mixture on to water, extracts the product with ethyl acetate, and purifies the crude product obtained after removal of the extraction agent with the methods usual in preparative organic chemistry, e.g. by chromatography on silica gel or crystallisation. Preferred solvent of the described reaction is dimethylformamide. Preferred alkali metal carbonate is caesium. carbonate.
The reaction conditions are very mild, many functional groups, such as e.g. the double bond, the nitro group, the alkoxycarbonyl group, the cyano group, halogen groups and alkoxy groups on aromatics are tolerated. The starting materialsxe2x80x94aza-heterocycles and alkyl and aryl halidesxe2x80x94are commercially available in large number. The conditions for the working up of the reaction are very simple to produce.
Under the assumption that caesium carbonate can be produced again from the extracted aqueous residue, the method is suitable to bind gaseous carbon dioxide on to simple commercially available starting materials, such as aza-heterocycles, especially indole and alkyl/aryl halides and thereby to produce valuable, energy-rich intermediate products.
In this sense, the said process is a valuable contribution to an environmentally-friendly chemistry.
On the basis of a simple practical carrying out of the reaction, the process procedure is also outstandingly suitable for a high throughput synthesis of heterocyclic carbamates since, by suitable combination of aza-heterocycles and alkyl or aryl halides in a carbon dioxide gasification apparatus, a plurality of synthesis reactions can take place in parallel.
Many of the compounds synthesised by the described process are new, their testing for suitability of use in the field of medicinal chemistry and plant protection chemistry is still outstanding.