The invention relates to a process for the preparation of mono- and oligoisocyanates by reacting primary amines with phosgene in the presence of a catalyst.
Isocyanates are industrial products which have a large number of uses in the field of polyurethane plastics. However, certain isocyanates are also used in the preparation of pharmaceutical active ingredients.
The synthesis of isocyanates by reacting amines with phosgene has been known for some time. In principal, two processes are described in the literature, one of which is carried out at atmospheric pressure and the other is carried out at increased pressure. Phosgenation under increased pressure is disadvantageous since it requires much more complex industrial apparatus to control the increased safety risk, the release of phosgene.
For sulfonyl isocyanates, U.S. Pat. No. 3,371,114 and U.S. Pat. No. 3,484,466 disclose a preparation process at atmospheric pressure in which a solution of a sulfonylamide and an isocyanate as catalyst in an inert solvent is reacted with phosgene. In the process, the corresponding sulfonylurea is formed as an intermediate, which reacts with phosgene to give the desired sulfonyl isocyanate.
Alkyl and aryl isocyanates are usually prepared by the phosgenation process, described, for example, in Houben-Weyl, Methoden der organischen Chemie [Methods in Organic Chemistry], 4th Edition, Volume E4, pages 741-751, Georg Thieme Verlag Stuttgart, 1983, from the corresponding amines in two phases at atmospheric pressure. In the first phase, the cold phosgenation, the amine is reacted with an excess of phosgene in very dilute solution and at low temperatures to give the corresponding carbamyl chloride, from which, in the second phase at elevated temperature, the hot phosgenation, the isocyanate forms. Aliphatic and cycloaliphatic primary amines are more difficult to phosgenate because of their increased basicity compared with aromatic amines, and lead to an increased formation of byproducts. A disadvantage of these processes is, in addition to the fact that the phosgenation is carried out in two phases, the formation of an intermediate solids suspension of sparingly soluble carbamyl chloride and amine hydrochloride, which in turn renders an increased dilution of the reaction medium necessary in order to prevent deposits and blockages of parts of the equipment. Because of the accumulation of solids which occurs, this process cannot be carried out continuously at atmospheric pressure. Furthermore, symmetrically N,Nxe2x80x2-substituted urea forms as a byproduct, the formation of which can only be suppressed at the expense of drastically reduced space-time yields.
Aliphatic and cycloaliphatic amines are frequently used in the form of their salts in the cold/hot phosgenation. However, these salts are sparingly soluble in the reaction medium, meaning that additional reaction stages and very long reaction times are necessary.
Furthermore, it is known from GB 1 114 085, U.S. Pat. No. 3,492,331 and H. Ulrich, Chemistry and Technology of Isocyanates, Wiley and Sons, 1996, pages 328-330, to optimize the reaction of primary amines with phosgene by the addition of catalysts such as dimethylformamide, phenyltetramethylguanidine, 2,4,6-trimethylpyridine or carbodiimidazole. Some of these catalysts must be used in equimolar amounts and form sparingly soluble salts under the reaction conditions.
It is an object of the present invention to provide a process, which can be used for aliphatic, cycloaliphatic, araliphatic and aromatic primary amines, for the preparation of the corresponding mono- and oligoisocyanates using phosgene which can be carried out either continuously or batchwise at atmospheric pressure, does not have the above disadvantages and provides the corresponding mono- and oligoisocyanates in good yields and high selectivities.
We have found that this object is achieved by a process for the preparation of aliphatic, cycloaliphatic, araliphatic and aromatic mono- and oligoisocyanates by phosgenation of the corresponding primary amines at atmospheric pressure, in which
a) a catalytic amount of a monoisocyanate (isocyanate a) is introduced into an inert solvent together with phosgene,
b) the primary amine is added, and
c) the resulting reaction mixture is reacted with phosgene.
The net equation underlying the process is given in scheme 1 below. 
The process according to the invention has the advantage that it can be used for a large number of amines. The phosgenation is carried out according to the invention, while avoiding a division into cold and hot phosgenation, in a narrow temperature interval and at atmospheric pressure, the intermediate formation of sparingly soluble suspensions being avoided. The desired isocyanate is formed in the process, with complete conversion of the amine, in high yields and high selectivity in significantly shortened reaction times without symmetrically substituted N,Nxe2x80x2-urea being formed from the amine as a byproduct. Since the formation of urea from the amine is not observed, it is possible by means of the process according to the invention to significantly increase the concentration of the amine in the reaction solution and thus the space-time yields. In addition, it is advantageous that the process according to the invention can be carried out either batchwise or continuously since there is no accumulation of solids.
The process according to the invention gives aliphatic, cycloaliphatic, araliphatic and aromatic mono- and oligoisocyanates of the formula I
R1xe2x88x92N=C=Oxe2x80x83xe2x80x83(I)
The radical R1 in formula I corresponds to the radical R1 in formula IV of the amines used in the process according to the invention, which are discussed later and to which reference is made here. Preference is given to preparing mono- and diisocyanates by the process of the invention. Of lesser importance in practice, but preparable in principle are isocyanates having 3 and more isocyanate groups.
The sole catalyst used is a monoisocyanate of the formula II (isocyanate a)
R2xe2x88x92N=C=Oxe2x80x83xe2x80x83(II)
or mixtures thereof, in which R2 is aliphatic, cycloaliphatic, aromatic or araliphatic radicals. These can be substituted by heteroatoms, or their carbon chains can be interrupted by heteroatoms, such as oxygen and sulfur. The radical R2 must, however, be inert toward phosgene, thus excluding radicals which carry NH, OH and SH groups. The aliphatic radicals can be arbitrarily branched or unbranched, saturated or unsaturated. They contain 3 to 30 carbon atoms, preferably 3 to 10 carbon atoms. Examples of aliphatic radicals are methyl, ethyl, propyl, n-butyl, isobutyl and sec-butyl.
Suitable cycloaliphatic radicals are those which have 3 to 20 carbon atoms, preferably 3 to 10 carbon atoms, such as, for example, cyclopentyl and cyclohexyl.
The aromatic radicals can be unsubstituted or arbitrarily substituted by alkyl or aryl substituents or heteroatoms. Preference is given to the aromatic radicals which are mono- or disubstituted. Examples of aromatic radicals are phenyl, chlorophenyl, o-, m- and p-tolyl.
Suitable araliphatic radicals are radicals having 7 to 12 carbon atoms, such as, for example, benzyl, although preference is given to a radical of the formula III

in which R3 and R4 can be identical or different and can be hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, in which case these may be substituted by heteroatoms, or their carbon chains can be interrupted by heteroatoms, such as oxygen and sulfur. The radicals R3 and R4 must, however, be inert toward phosgene, thus excluding radicals carrying NH, OH and SH groups. The aliphatic radicals can be arbitrarily branched or unbranched, saturated or unsaturated. They contain 1 to 30 carbon atoms, preferably 1 to 10 carbon atoms. Examples of aliphatic radicals are methyl, ethyl, propyl, n-butyl, isobutyl and sec-butyl.
Suitable cycloaliphatic radicals are those which have 3 to 20 carbon atoms, preferably 3 to 10 carbon atoms, such as, for example, cyclopentyl and cyclohexyl.
The aromatic radicals can be unsubstituted or arbitrarily substituted by alkyl or aryl substituents or heteroatoms. Preference is given to the aromatic radicals which are mono- or disubstituted. Examples of aromatic radicals are phenyl, chlorophenyl, o-, m- and p-tolyl. R5 is fluorine, chlorine, bromine or a C1- to C4-alkyl chain which may optionally be interrupted by a heteroatom, for example oxygen or sulfur. Preference is given to the monoisocyanate (isocyanate a), a linear aliphatic alkyl isocyanate, particularly preferably a linear aliphatic alkyl isocyanate having 3 to 10 carbon atoms, where the alkyl chain may optionally be branched, particularly preferably n-butyl isocyanate. In the case of the preparation of monoisocyanates by the process according to the invention, it is also possible to use the monoisocyanate desired as product in catalytic amounts as isocyanate a. It is, however, preferable to use an isocyanate a which is not identical to the product (isocyanate of the formula (I)) as catalyst.
The isocyanate a is generally used in a catalytic amount of from 0.01 to 25 mol %, preferably 0.5 to 20 mol %, particularly preferably 1 to 15 mol %, based on the amine.
In step a) of the process according to the invention, the isocyanate a is introduced into a solvent which is inert toward phosgene. Preferred solvents are hydrocarbons. Particular preference is given to mono- or polysubstituted aromatic hydrocarbons, such as toluene, o-, m- or p-xylene, ethylbenzene, chlorobenzene or 1,2-, 1,3- or 1,4-dichlorobenzene or mixtures thereof. Particular preference is given to xylenes, chlorobenzene and dichlorobenzenes as solvent.
The process according to the invention is carried out at atmospheric pressure and generally at a reaction temperature, which is largely constant over the three steps of the process a), b) and c), of from 20 to 200xc2x0 C., preferably from 20 to 150xc2x0 C., particularly preferably from 50 to 120xc2x0 C.
The monoisocyanate (isocyanate a) dissolved in the inert solvent is, in step a) of the process according to the invention, heated to the reaction temperature and mixed with an excess of phosgene, based on the monoisocyanate. The molar ratio between phosgene and isocyanate a is preferably 100:1 to 5:1. Particular preference is given to using phosgene in an excess of 20:1 to 5:1, based on isocyanate a.
The phosgene can be used in the process according to the invention in steps a) and c) in gaseous form or in condensed form, preference being given to introducing the phosgene in gaseous form.
In the process according to the invention, suitable primary amines are amines of the formula IV
R1xe2x88x92NH2xe2x80x83xe2x80x83(IV)
which are obtainable by methods known from the literature or as a commercially available product.
R1 stands for aliphatic, cycloaliphatic, aromatic or araliphatic radicals. These can be substituted by heteroatoms, or their carbon chains can be interrupted by heteroatoms, such as oxygen and sulfur. Radicals which contain OH and SH groups are excluded. Substitution by amino groups, on the other hand, is possible and leads to di- or oligoisocyanates, preference being given to diisocyanates. The aliphatic radicals can be arbitrarily branched or unbranched, saturated or unsaturated. They contain 3 to 30 carbon atoms, preferably 3 to 10 carbon atoms. Examples of aliphatic radicals are propyl, butyl, pentyl and hexyl. Suitable cycloaliphatic radicals are those having 3 to 20 carbon atoms, preferably those having 3 to 10 carbon atoms, such as cyclopentyl and cyclohexyl.
The aromatic radicals can have 4 to 10 carbon atoms, can be heteroaromatic radicals, and unsubstituted or arbitrarily substituted by alkyl or aryl substituents or heteroatoms. The aromatic radicals are preferably mono- or disubstituted. Examples of aromatic radicals are phenyl and chlorophenyl, o-, m-, p-tolyl, furfuryl, thiophenyl and pyrrolyl.
Suitable araliphatic radicals are radicals having 7 to 12 carbon atoms, such as, for example, benzyl, although preference is given to a radical of the formula V 
in which R6 and R7 can be identical or different and can be hydrogen or an aliphatic, cycloaliphatic or aromatic radical, in which case these can be substituted by heteroatoms, or their carbon chains can be interrupted by heteroatoms, such as oxygen and sulfur. The radicals R6 and R7 must, however, be inert toward phosgene, meaning that radicals carrying NH, OH and SH groups are excluded. The aliphatic radicals can be arbitrarily branched or unbranched, saturated or unsaturated. They contain 1 to 30 carbon atoms, preferably 1 to 10 carbon atoms. Examples of aliphatic radicals are methyl, ethyl, propyl, n-butyl, isobutyl and sec-butyl.
Suitable cycloaliphatic radicals are those which have 3 to 20 carbon atoms, preferably 3 to 10 carbon atoms such as, for example, cyclopentyl and cyclohexyl.
The aromatic radicals can be unsubstituted or arbitrarily substituted by alkyl or aryl substituents or heteroatoms. Preference is given to the aromatic radicals which are mono- or disubstituted. Examples of aromatic radicals are phenyl, chlorophenyl, o-, m- and p-tolyl. R8 is a halogen atom (F, Cl, Br) or a C1- to C4-alkyl chain, which may optionally be interrupted by a heteroatom, for example oxygen or sulfur. Primary amines of the formula IV which can be used are also amines in enantiomerically pure, optically active form or mixtures of the enantiomers. The process according to the invention advantageously leads during the reaction and the work-up to only a low degree of racemization, which is generally below 2%.
In the process according to the invention, preference is given to using cycloaliphatic, araliphatic and aromatic amines, in particular those which are further processed in industrial processes, such as, for example, hexamethylenediamines, cyclohexylamine, isophoronediamine, toluylenediamine, aniline, and optically active amines, such as, for example, R-(+)- and S-(xe2x88x92)-phenylethylamine.
In step b) of the process according to the invention, the primary amine is added to the solution of the monoisocyanate (isocyanate a), saturated with phosgene, preferably in an inert solvent. This can be carried out, for example, in the presence of a stream of inert gas, for example nitrogen. Preferred solvents are the solvents used in step a) of the process according to the invention. Particular preference is given to using the same solvent as in step a). The resulting reaction mixture is then reacted with phosgene in step c) of the process according to the invention.
The molar ratio between primary amine and the total amount of the amount of phosgene introduced in steps a) and c) is 1:10 to 1:1, particular preference being given to introducing phosgene in an amount of from 120 to 180 mol %, based on the amine.
The process according to the invention can in principle be carried out both continuously and batchwise, preference being given to a continuous operation. The process can be carried out in any desired apparatus which is suitable for a reaction with phosgene. For example, a phosgenation apparatus is used which comprises an attached carbonic acid condenser or a downstream battery of high-efficiency condensers for the condensation of phosgene.
For the preferred continuous procedure, a phosgenation apparatus is used which comprises a main reactor and after-reactor, a stripping column and, connected downstream therefrom, a condenser. In the case of the continuous procedure, a mixture of the desired isocyanate of the formula I, the catalytic amounts of the isocyanate of the formula II (isocyanate a) and phosgene in the inert solvent is preferably initially introduced.
After an after-reaction, excess phosgene and solvent are generally stripped out at temperatures from 30 to 80xc2x0 C., preferably 40xc2x0 C. to 60xc2x0 C., condensed in the condenser and returned together to the after-reactor.
The reaction product is worked up using methods known to the person skilled in the art. Preferably, the desired isocyanate of the formula I is isolated by fractional distillation. The isocyanate a used as catalyst is preferably recovered by distillation and can be reused for further batches. The desired mono- and oligoisocyanates can be obtained in the process in yields of generally 60 to 95%, based on the primary amine used.
The examples below illustrate the invention further.