US3678042A - Process for the manufacture of aryloxazoles - Google Patents

Abstract

The invention provides a new process for preparation of aryloxazoles by ring closure reaction between an o-hydroxy-amino benzene and a carboxylic acid. The improvement over known processes consists in performing the reaction in a two-step heating procedure and in the presence of small amounts of specific amines, preferably non-aromatic cyclic nitrogen bases, having a Pk-value of at least 7. The reaction products are valuable optical whitening agents.

Description

United States Patent Matter July 18, 1972 [54] PROCESS FOR THE MANUFACTURE 213g: meager e: :11. "323138; 3 xqz ae ere 0F ARYLO OLES 3,293,258 12/1966 Siegrist et al.... .....260/307 D [72] Inventor: Erich Matter, Basel, Switzerland 3,427,307 2/1969 Schinzel et a]. ..260/240 D [73] Assignee: Ciba Limited, Basel, Switzerland Primary Examiner-John D. Randolph [22] F l d: P 1969 Attorney-Harry Goldsmith, Joseph G. Kolodny and Mario A. 211 App]. No.: 862,442

[ 30] Foreign Application Priority Data [57] ABSTRACT The invention provides a new process for preparation of Oct. 7, 1968 Switzerland ..14932/68 aryloxazoles y g closure reaction between an y y amino benzene and a carboxylic acid. The improvement over [52] U.S. Cl. ..260/240 CA, 260/307 D known processes consists in performing the reaction in a [51] [Ill- Cl. ..C07tl 85/48 step heating procedure and in the presence of small amounts [58] Field of Search ..260/240 D, 307D f ifi i f r bl non-aromatic cyclic nitrogen bases, having a P -value of at least 7. The reaction products [56] References Cited are valuable optical whitening agents.

UNITED STATES PATENTS 9 Claims, No Drawings 3,095,421 6/1963 Liechti ..260/304 PROCESS FOR THE MANUFACTURE OF ARYLOXAZOLES It is known that aryloxazoles, that is to say oxazoles of which the two adjacent carbon atoms of the oxazole ring at the same time are ring members of an aromatic-carbocyclic six-membered ring, are appropriately manufactured from o-hydroxyaminoaryl compounds and carboxylic acids. Herein a total of two molecules of water are eliminated from one o-hyclroxyamino group and one carboxylic acid group, for example, in the simplest case, in accordance with the scheme A particularly advantageous and economical process for the manufacture of aryloxazoles by reaction of o-hydroxyaminoaryl compounds with aliphatic dicarboxylic acids containing at least four carbon atoms or with monocarboxylic or dicarboxylic acids containing one to two carbocyclic or heterocyclic rings with five to six ringmembers each, in the presence of a solvent which is chemically inert towards the reagents, has now been discovered. This process is characterized in that the reaction of the reagents is carried out in the presence of less than stoichiometric amounts of a nitrogen base from the group of (a) secondary or tertiary, cyclic, nonaromatic nitrogen bases or (b) the primary or secondary aminobenzenes or (c) the primary or secondary, aliphatic or cycloaliphatic, amines or (d) basic nitrogen compounds which contain the atom grouping of formula IIIII C N/ \\N at least once, as well as in the presence of small amounts of boric acid, by first heating the reaction mixture to temperatures of at least 150 C and then, with gradual increase of temperature, to temperatures of at least 200 C. The specification of a minimum temperature of 150 C for the first reaction stage of course denotes a temperature in the range of between 150 and about 200 C, whilst the upper limit for the temperature range applicable from 200 C onwards is set by the incipient decomposition of the reagents and reactionproducts.

One embodiment of this process consists of carrying out the reaction of the reagents in the presence of less than stoichiometric amounts of a nitrogen base from the group of the (a) secondary or tertiary, cyclic, non-aromatic nitrogen bases, or (b) the primary or secondary aminobenzenes, or (c) the primary or secondary aliphatic or cycloaliphatic amines, as well as small amounts of boric acid, by heating the reaction mixture initially to temperatures of at least 150 C and then, with gradual increase to temperatures of at least 200 C.

As can be seen from the reaction conditions defined above, one of the essential characteristics of this process is the use of selected nitrogen bases, whilst another criterion is the use, connected therewith, of less than stoichiometric amounts of these nitrogen bases. According to this, possible amounts of nitrogen base are quite generally those lying between, say, 0.05 and 20, preferably 0.5 to 10, percent by weight, relative to aminophenol to be employed. In practice, however, significantly lower amounts of nitrogen base are normally employed, since the nitrogen base evidently possesses a catalytic effect. Thus, though larger amounts are, within the framework of the above-mentioned limits, without harmful effect on the course of the reaction, they are normally superfluous and uneconomical. In particular, amounts of 0.2 to 2 percent by weight (calculated relative to aminophenol) are completely sufficient in the case of the nitrogen bases with a pK-value of at least 7 which are preferentially to be employed. In practice it is of interest to carry out the reaction defined above in the presence of such nitrogen bases as belong to the group of the (a) secondary or tertiary, cyclic, non-aromatic, S-membered to 8-membered nitrogen bases containing one to two ring nitrogen atoms, or the (b) primary or secondary aminobenzenes or the (c) primary or secondary aliphatic amines with one to 12 carbon atoms and one to three amino groups. in order to achieve particularly favorable results as to yield it has proved very advantageous to employ nitrogen bases of the nature defined which have a pK-value of at least 7 (measured in ethylene glycol monomethyl ether/water).

Taking into account the manufacture of compounds of industrial interest and in an appropriate embodiment, the especially preferred process is to be defined in that according to it (1) a carboxylic acid from the series of the (i) dicarboxylic acids of benzene, naphthalene, stilbene, thiophene or furane, (ii) monocarboxylic acids of benzene or diphenyl, or (iii) of the aliphatic dicarboxylic acids having a carbon atom chain of 4 carbon atoms, is reacted with (2) a hydroxyarylamino compound of formula wherein R denotes the phenyl group or a residue C I-1 and occupies the positions 4 or 5, and n represents an integer from 1 to 5, in the presence (3) of a nitrogen base having a pK-value of at least 7, from the series of the (x) secondary or tertiary, cyclic, non-aromatic nitrogen bases containing one to two rings with five or six ring members and one to two ring nitrogen atoms, (xx) primary or secondary aliphatic or cycloaliphatic amines with one to 12 carbon atoms and one to three amino groups or (xxx) guanidines, with this reaction being carried out in the presence of small amounts of boric acid, by first heating the reaction mixture to temperatures of at least C and then, with gradual increase of temperature, to temperatures of at least 200 C.

For further explanation of the bases to be used there shOuld be mentioned that here secondary or tertiary cyclic non-aromatic nitrogen bases are to be understood as compounds of which the secondary or tertiary nitrogen atoms, respectively, are present as ring members. In general these non-aromatic nitrogen-heterocyclic compounds possess six ring members, but it is also entirely possible to employ compounds containing five, seven and eight ring members (for example bicyclic types). Furthermore one is usually dealing with compounds with one to two ring nitrogen atoms. Typical representatives of S-membered nitrogen bases of this nature are for example pyrrolidine, pyrazolidine, imidazolidine and its N-alkyl derivatives, and typical representatives of 6-membered nitrogen bases are the piperidines and piperazines as well as their N- alkyl derivatives, and also morpholine types. Amongst the higher-membered cyclic nitrogen bases, the bicyclic types such as for example tetrahydroquinoline or bicyclic endoalkyl types such as quinuclidine and l,4-diazabicyclo-[2,2,2]- octane should be mentioned as examples.

Primary and secondary aminobenzenes can in principle be used, though they produce lower yields because of their pK- value being low in most cases. They are represented by bases such as aniline, toluidines, xylidines, phenylenediamines and their N-alkyl derivatives and compounds of analogous structure. in general one is here dealing with monoamines or diamines.

in the case of the primary or secondary aliphatic amines, alkylamines (straight-chain or branched) with one to 12 carbon atoms and one to three amino groups of primary or secondary nature are preferentially used. In addition, however, polyalkylenepolyamines (for example diethylenetriamine or triethylenetetramine), aliphatic amines with hydroxyl groups (for diethanolamine) or alkoxy groups, or such amines which in addition to the obligatory primary or secondary amino groups additionally carry tertiary amino groups (dialkylaminoalkylamines) are also suitable without difficulty. By cycloaliphatic amines there should here be understood those of which the amino group is bonded to a cycloaliphatic ring (for example cyclohexylamine).

For the possible group of nitrogen bases possessing the structural element melamine, guanidine, dicyandiamide and biguanide may be mentioned as appropriate base substances.

As examples of amines which can advantageously be used, the following may be mentioned (pK-values given in brackets): piperidine (9.72), N-methylpiperidine, N-hydroxyethylpiperidine, pyrrolidone (9.82), N-methylpyrrolidone, N-methylpiperazine (9.04), N,N-dimethylpiperazine, N- hydroxyethylpiperazine, N-aminoethylpiperazine, cyclohexylamine (9.53), morpholine (7.97), methylamine.HCl (9.94), dimethylamine, diethylamine (9.70), butylamine (9.55), diisopropylamine (9.70), triethylamine (9.06), ethanolamine (9.01 N-ethylethanolamine, ethylenediamine. HCl (6.41), diethylenetriamine (9.52), guanidine acetate, aminoguanidine. HCO diphenylguanidine (7.66), diazabicyclo-[2,2,2]-octane and tetrahydroquinoline.

The reaction according to the present process inherently takes place in two stages, that is to say condensation to give the acyl compound first occurs, and a ring closing reaction occurs in a second stage. Accordingly, the reaction mixture is first heated to temperatures of at least 150 C to about 200 C and is only thereafter (after a certain dwell time, depending on the nature of the reagents) brought to the minimum temperature of about 200 C required for the ring closing reaction, with the temperature being raised slowly. The practical working range for the ring closing reaction stage is about 200 to 260 C, but it is entirely possible to exceed 260 C if the components are sufficiently heat-stable.

lf in the process described above aliphatic carboxylic acids are used as starting substances, they contain two carboxylic acid grOups and at least four carbon atoms. The bridge member between the two carboxylic acid groups can be a branched or unbranched, saturated or unsaturated, aliphatic hydrocarbon residue. This residue can however further contain substituents, for example halogen atoms such as chlorine, amino groups, alkoxy groups such as methoxy and especially hydroxyl groups. As examples of aliphatic dicarboxylic acids, adipic acid, dichlorosuccinic acid, tartaric acid, aspartic acid, thiomalic acid, but especially succinic acid, fumaric acid and malic acid may be mentioned. It should be noted that under certain circumstances changes in the bridge member between the two carboxylic acid groups can also occur on carrying out the present process, for example splitting off of a further molecule of water from tartaric acid and malic acid or splitting off of ammonia from aspartic acid, whereby carbon-carbon double bonds are produced.

The process according to the invention is particularly valuable for the reaction of cyclic-aromatic carboxylic acids. In this case the ring systems can contain one or two carboxylic acid groups and two or preferably one carbocyclic or heterocyclic ring. Carbocyclic rings are aromatic, as is the case for naphthalene-, diphenyland benzene-mono-carboxylic and dicarboxylic acids. Heterocyclic rings preferably contain five ring members, namely 4 carbon atoms and an oxygen or sulphur atom. Monocyclic benzene-, furaneor thiophenecarboxylic acids can especially be used. The heterocyclic rings and above all the aromatic carbocyclic rings can, additionally to the carboxylic acid groups, contain yet further substituents, for example halogen atoms such as bromine or chlorine, alkyl groups with one to four carbon atoms such as methyl, ethyl,

isopropyl, or tertiary butyl, and alkoxy groups with one to two carbon atoms.

A preferred embodiment of the present invention consists in reacting a carboxylic acid component which represents a carboxylic acid, containing one to two carboxyl groups, of benzene, diphenyl, naphthalene, stilbene, styrene, thiophene or furane, or the analogues of these carboxylic acids containing one to three alkyl groups having one to four carbon atoms each, or an aliphatic dicarboxylic acid containing 4 carbon atoms, in approximately equivalent amount with an o-hydroxyaminophenol which can optionally be substituted by one to three alkyl groups with one to 18 carbon atoms, an alkoxy group with one to four carbon atoms, a carbalkoxy group with one to 12 carbon atoms, a halogen atom or a phenyl group.

Practical industrial interest here attaches to the reaction of approximately equivalent amounts of a dicarboxylic acid of benzene, diphenyl, naphthalene, stilbene, thiophene or furane with a o-hydroxyaminobenzene which can optionally be substituted by one to three alkyl groups having one to four carbon atoms or by a phenyl group.

As examples of the aromatic-cyclic carboxylic acids which are possible starting materials there may be mentioned: naphthalene-lor -2-carboxylic acid, naphthalene-1,4- or l,5-dicarboxylic acid, diphenyl-4,4-dicarboxylic acid, stilbene-4,4-dicarboxylic acid, cinnamic acid, benzene carboxylic acid, 3- or preferably 4-methylbenzenecarboxylic acid, benzene-1,3- or preferably -1,4-dicarboxylic acid, furane-2- carboxylic acid, thiophene-Z-carboxylic acid, 3,4- dimethylthiophene-2,5-dicarboxylic acid, 3,4-diphenylthiophene-2,5-dicarboxylic acid, diphenyl-4-carboxylic acid, 5- phenyl-thiophene-Z-carboxylic acid and furane-2,5-dicarboxylic acid.

Particularly valuable results are achieved with the dicarboxylic acids of formula wherein X denotes an oxygen atom or a sulphur atom, that is to say with furaneand thiophene-2,5-dicarboxylic acid, and it is known that it is particularly the bis-benzoxazoles obtainable from these dicarboxylic acids, above all from thiophenedicarboxylic acid, and o-hydroxyaminobenzenes which are optionally further substituted, which are valuable optical brighteners.

As further starting substances, the present process requires hydroxyaminoaryl compounds which contain the hydroxyl group and the (primary) amino group in an adjacent position to one another. Possible substances are for example 1,2- or 2,l-hydroxyaminonaphthalenes or preferably o-hydroxyaminobenzenes which may contain yet further substituents, for example a halogen atom such as chlorine, an alkoxy group such as methoxy or ethoxy, a phenyl group, an alkyl group such as methyl, ethyl, isopropyl, tertiary butyl or 1,1,15,3- tetramethylbutyl, and also two methyl groups.

Preferred substances are o-hydroxyaminobenzene which does not contain any further substituents, and o-hydroxyaminobenzenes which as further substituents contain one to two alkyl groups, an alkoxy group, a halogen atom or a phenyl group. Important substances amongst these are the o-hydroxyaminobenzenes of formula (I) [see above], wherein, in this formula, the phenyl group representing R is preferably in position 5, whilst the group -(C,, ,H is preferably in position 4, that is to say hydroxyaminobenzenes of formulas l a) no (lb) are predominantly employed.

The reaction according to the present process is carried out in a diluent which as such must be liquid at the temperatures of the entire process and which does not participate in the reaction. At the same time it is however in no way necessary for all the products occuning in the reaction, that is to say the reagents used as starting substances, intermediate stages and final substances, to be largely or even completely dissolved. In particular, the carboxylic acid amides which as a rule are formed as an intermediate can be sparingly soluble to practically insoluble in such a diluent without this having a disadvantageous effect. Since the diluent should be present also at the high temperature at the end of the course of the reaction, it is advisable to use such an inert organic solvent for diluting the reaction mixture as has a boiling point of at least 200 C under normal pressure. Admittedly it is also possible to use a diluent or solvent boiling at lower temperatures at the start of the reaction, to allow this to distil off and to replace it at the correct time by a higher-boiling diluent or solvent, and water can even be used as the first diluent; however, economic reasons alone as a rule suggest working from the start with a high-boiling diluent which does not have to be replaced or renewed. As examples of particularly suitable solvents there may be mentioned tetrahydronaphthalene, mixtures of diphenyl and diphenyl-ether and especially trichlorobenzenes, and here trichlorobenzene mixtures such as are commercially available can also be used without difficulty. Accordingly, the reaction is preferably carried out in the presence of a diluent which represents a halogenobenzene, preferably a trichlorobenzene, alkylbenzene, halogenated alkylbenzene, partially hydrogenated naphthalene or chlorinated naphthalene, which is liquid at room temperature and boils at not less than 200 C, or diphenylether or diphenyl.

Of the two starting substances, from which the oxazoles are produced, equivalent amounts are appropriately employed, that is to say one mol of monocarboxylic acid per one mol of hydroxyaminoaryl compound and one mol of dicarboxylic acid per two mols of hydroxyaminoaryl compound, or amounts which deviate therefrom by at most 5 mol percent in one direction or the other. The amount of the diluent should be such that the reaction mixture can without difficulty be kept homogeneous by stirring devices of the usual construction, even if insoluble products, especially the carboxylic acid amides produced as an intermediate stage, arise. Depending on the choice of the starting substances, there can be differences in the particularly advantageous amounts of diluents. ln general, good results are achieved if the amount of diluent used is about half to twice the amount of the two starting substances.

The catalyst for splitting off water is employed in the usual amounts, that is to say about 0.5 to percent of boric acid, calculated relative to the amount by weight of the condensation components.

Favorable results are achieved if the nitrogen base and the carboxylic acid are first of all allowed to act on one another. Thus, for example, the base and the carboxylic acid can first of all be stirred with one another in the diluent, the hydroxyaminoaryl compound and the catalyst for splitting off water added, and the mixture then slowly heated further until the acid amide is first formed and thereafter ring closure takes place at an even higher temperature.

A simpler and particularly advantageous procedure is first to warm a mixture which has been obtained by combining the nitrogen base with a carboxylic acid of the indicated composition and a hydroxyaminoaryl compound of the indicated composition in a liquid diluent to temperatures of 150 to 200 C until approximately one molecule of water has been split off per molecule of hydroxyaminoaryl compound, and then to complete the reaction by heating to even higher temperatures, up to about 260 C, with water being continuously removed by distillation.

In order to avoid undesired oxidations it is advisable to avoid contact of the reaction medium with oxygen, that is to say to work with exclusion of air, appropriately under nitrogen. The addition of antioxidants such as for example amylphenol has proved particularly advantageous. This not only increases the yield but also greatly represses the formation of by-products which act as fluorescence extinguishers, that is to say increases the purity of the final products.

As can be seen from the preceding explanations, the carboxylic acid amide is formed in the first stage of the present process and the oxazole in the second stage. The minimum temperature at which the second stage takes place can show certain differences from case to case within the specified limits. It is advisable to allow the two reaction stages to take place successively, that is to say not to warm the mixture beforehand to the ring closing temperature before the carboxylic acid amide has substantially formed.

The oxazoles are obtained in very the present process.

good yield and purity by EXAMPLE 1 2,5-Di-[benzoxazolyl-(2')]-thiophene Six hundred grams of trichlorobenzene (isomer mixture), 219 g of l-hydroxy-Z-arninobenzene, 172 g of thiophene-2,5- dicarboxylic acid, 6 g of boric acid and l g of piperidine are stirred in the reaction vessel, with exclusion of air. The pale yellow suspension is heated to 220 C over the course of 4 hours, during which the color changes to yellow, and at 160 C the distillation of piperidine/water mixture commences. The reaction mixture transiently becomes less thick and changes at 180 C into the thick yellow crystal sludge of the diamide. Finally the mixture is stirred for 3 hours at 220 to 222 C. The yellow crystals dissolve and the brown solution of the oxazole is obtained. In total, 140 to 260 ccs of distillate are obtained, with trichlorobenzene also distilling over from 180 C onwards. After cooling to about 150 C the reaction product beings to separate out as crystals. Four hundred grams of isopropanol are carefully allowed to run in and the mixture is cooled to room temperature. The yellow crystals are filtered 01f, washed with isopropanol and dried in a vacuum drying cabinet at to C. The yield obtained is 305 to 308 g of 2,5-di-[benzoxazolyl-(2')]-thiophene, corresponding to 96 to 97 percent of theory. Melting point: 221 to 222 C.

For additional purification the product can be dissolved in a six-fold amount of trichlorobenzene, treated at C with an adsorbent, clarified by filtration and concentrated.

The pale yellow crystals, having a melting point of 223 C, are completely precipitated by adding isopropanol.

If instead of l g of piperidine an amount of 5 g of piperidine is used, the desired product is obtained in a yield of 94.8 percent of theory.

If the experiment is carried out with the addition of only 0.2 g of piperidine, the yield is 93.5 percent of theory. Melting point: 222 C.

EXAMPLE 2 2,5-Di-[ benzoxazolyl-( 2 ]-thiophene A mixture of 600 g of trichlorobenzene, 219 g of 2- aminophenol, 172 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid, 5 g of N-methylpiperidine and 5 g of amylphenol is heated to 220 C over the course of 4 hours with exclusion of air. A golden brown solution is obtained and a mixture of methylpiperidine/water/trichlorobenzene distils off. Finally the mixture is stirred for 3 hours at 220 to 222 C.

Four hundred grams of isopropanol are carefully allowed to run in at 150 C. The mixture is cooled to room temperature and the product filtered off and washed with isopropanol. The 2,5-di-[benzoxazolyl-(2')]-thiophene is obtained in the form of yellow crystals in a yield of 97 percent of theory. The melting point is at 221 to 222 C.

If instead of the above-mentioned amount of the piperidine derivative 20 g of N-methylpiperidine are employed, the yield is 96.3 percent, and when using only 1 g of N-methylpiperidine a yield of 95.4 percent is achieved.

2,5-Di-[benzoxazolyl-(2')]-thiophene A mixture of 600 g of trichlorobenzene, 219 g of oaminophenol, 172 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of morpholine is heated to 220 C over the course of 4 hours with complete exclusion of air. Thereafter the mixture is stirred for 3 hours at 220 to 222 C and a golden brown solution is obtained.

Four hundred grams of isopropanol are allowed to run in at 150 C, the mixture is cooled to room temperature, and the product is filtered off and washed with isopropanol. The 2,5- di-[benzoxazolyl-(2)]-thiophene is obtained in a yield of 303 g or 95.3 percent of theory. Pure yellow crystals of melting point 221 C.

EXAMPLE 4 2,5-Di-[benzoxazolyl-(2)]-thiophene A mixture of 600 g of trichlorobenzene, 219 g of oaminOphenol, 172 g of 2,S-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of N,N'-dimethylpiperazine is heated to 220 C over the course of 4 hours, the process being carried out with absolute exclusion of air. A golden brown solution is obtained and from 160 C onwards a mixture of dimethylpiperazine/water/trichlorobenzene distils off. Thereafter the mixture is stirred for a further 3 hours at 220 to 222 C. 400 g of isopropanol are run in at about 150 C. The mixture is cooled to room temperature, and the product filtered off and washed with isopropanol. The di-[benzoxazolyl-(2')]- thiophene is obtained in a yield of 305.7 g, corresponding to 96 percent of theory. The yellow crystals melt at 221 C.

If instead of the dimethylpiperazine 2.5 g of N-methylpiperazine are used, the reaction product is obtained in a yield of 95.2 percent.

EXAMPLE 5 2,5-Di-[benzoxazolyl-(2)]-thiophene A mixture of 600 g of trichlorobenzene, 219 g of oaminophenol, 172 g of 2,S-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of hydroxyethylpiperazine is heated to 210 C over the course of 3 hours and to 220 C over the course ofa further hour. After transient separating-out of the yellow diamide compound, a brown solution is formed. The mixture is stirred for 3 hours at 220 to 222 C. Four hundred grams of isopropanol are carefully allowed to run in at 150 C, the crystal sludge is cooled to room temperature, and the product is filtered off and washed with isopropanol. The di-benzoxazolyl-thiophene is obtained in a yield of 302 g. Melting point 221to 221.4C.

If the hydroxyethylpiperazine in the reaction mixture is replaced by an equal quantity of hydroxyethylpiperidine, the same reaction product is obtained in a yield of 305 g or 96 percent oftheory.

EXAMPLE 6 2,5-Di-[benzoxazolyl-(2')]-thiophene A mixture of 600 g of trichlorobenzene, 220 g of l-hydroxy- 2-aminobenzene, 172 g of 2,S-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of ethylethanolamine is heated with exclusion of air, as in the previous examples. The 2,5-di- [benzoxazolyl-(2)]-thiophene is obtained in a yield of 301 g or 94.6 percent of theory. Melting point 220 C. If 3 g of diethylamine are used as the amine additive, a yield of 95.3 percent of theory is obtained.

EXAMPLE 7 2,5-Di-[benzoxazolyl-(2)]-thiophene A mixture of 600 g of trichlorobenzene, 218 g of l-hydroxy- 2-aminobenzene, 173.5 g of2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of piperazine is heated with exclusion of air in accordance with Example 1, and worked up. The yield is 295 g or 92.7 percent of theory. If instead of piperazine, aminoethylpiperazine is used in the following mix: 600 g of trichlorobenzene, 220 g of l-hydroxy-Z-aminophenol, 172 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of aminoethylpiperazine, the above-mentioned reaction product is obtained in a yield of 299 g or 94.2 percent of theory.

EXAMPLE 8 2,5-Di-[benzoxazolyl-(2)]-thiophene A mixture of 600 of trichlorobenzene, 219 g of l-hydroxy- Z-aminobenzene, 172 g of 2,S-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of ethylenediamine is heated in accordance with Example 1, with exclusion of atmospheric oxygen.

lsopropanol is added, the crystal sludge is filtered at room temperature and the product washed with isopropanol.

The dibenzoxazolylthiophene is obtained in a yield of 91.2 percent oftheory. Melting point 218 C.

If instead of ethylenediamine the same amount of ethanolamine is used, a yield of 90.1 percent of theory is obtained.

EXAMPLE 9 2,5-Di-[benzoxazolyl-(2')]-thiophene lfa mixture of 600 g oftrichlorobenzene, 219 g of l-hydroxy-2-aminobenzene, 172 g of 2,S-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of aniline is reacted analogously to Example the desired product is obtained in a yield of 90.1 percent oftheory. Melting point 220 C.

lfa mixture of 600 g of trichlorobenzene, 218 g of l-hydroxy-2-aminobenzene, 173.5 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of N-methylaniline is correspondingly reacted, a yield of 91.2 percent of theory is obtained. Melting point 220 C.

EXAMPLE 10 2,5-Di-[benzoxazolyl-(2)l-thiophene The dibenzoxazolylthiophene is obtained in a yield of 89.5 percent by reaction, in accordance with the instruction of Example l, of 600 g of trichlorobenzene, 218 g of l-hydroxy-2- aminobenzene, 173.5 g of 2,S-thiophenedicarboxylic acid, 5 g of boric acid and 3 g of tetrahydroquinoline. Melting point 220 C.

EXAMPLE 1 1 2,5-Di-[5-tert.butylbenzoxazolyl-(2)]-thiophene A mixture of 266 g of l-hydroxy-2-amino-4-tertiary butylbenzene, 138.5 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid, 350 g of trichlorobenzene and 2 g of piperidine is heated to 210 C over the course of 4 hours with exclusion of air. The temPerature is raised to 220 C over the course of a further hour and finally the mixture is stirred at 220 to 222 C for 3 hours.

Three hundred grams of isopropanol are slowly allowed to run into the clear brown reaction mixture at C.

The crystal sludge is filtered off at room temperature, washed with a total of 900 g of isopropanol and dried in a vacuum drying cabinet.

The 2,5-di-[5-tert.butylbenzoxazolyl-(2')]-thiophene is obtained in the form of pale yellow luminous crystals, in a yield of 327 g or 95 percent oftheory. Melting point 199 to 200 C.

EXAMPLE 12 2-(4-Methylphenyl)-5-tertiary butyl-benzoxazole A mixture of 272 g oF p-toluic acid, 330 g of lhydroxy-Z- amino-4-tert.butylbenzene, 10 g of boric acid, g of trichlorobenzene and 3 g of piperidine is stirred with complete exclusion of air and heated to 200 C over the course of 4 hours. At 150 C a mixture of water and piperidine begins to distil olf.

The temperature is raised to 220 C over the course of a further hour and the mixture is finally stirred for a further 2 hours at 220-225 C. After cooling to 120 C, 200 g of isopropanol are allowed to run in.

The mixture is cooled to C and the crystal sludge is filtered off on a porcelain suction filter. The crystals are washed with a total of 350 g of cold isopropanol.

The yield is 481 g or 90.6 percent of theory. Melting point of the white greyish-tinged crystals: 1 14 C.

If instead of the piperidine 3 g of N-methylpiperidine are used, a yield of 92.8 percent of theory is obtained.

EXAMPLE l3 4-Benzoxazolyl-(2)-diphenyl-( 1,1

A mixture of 205.5 g of diphenyl-4-carboxylic acid, 109 g of 1-hydroxy-2-aminobenzene, 5 g of boric acid, 750 g of trichlorobenzene and 2 g of methylpiperidine is heated to 210 C over the course of 4 hours with stirring and exclusion of air. The temperature is raised to 220 C over the course of a further hour and the mixture is finally stirred for 3 hours at 220 to 225 C.

Four hundred grams of isopropanol are carefully allowed to run in a 150 C and the mixture is cooled to room temperature.

The crystal sludge is filtered off and washed with isopropanol. The desired product is obtained in the form of almost colorless crystals in a yield of 229 g. Melting point 139.4 to 139.6 C.

EXAMPLE 14 2,5-Di-[benzoxazolyl-(2)]-furane A mixture of 220 g of 1-hydroxy-2-aminobenzene, 156 g of 2,5-furanedicarboxylic acid, 5 g of boric acid, 600 g of trichlorobenzene and 3 g of piperidine is heated to 210 C over the course of 4 hours with exclusion of air. A mixture of water and piperidine beings to distil off at about 150 C. The temperature is raised to 220 C over the course of a further hour and the mixture finally stirred for 2 hours at 220 to 225 C. In total, 135 ml of distillate containing 65 ml of trichlorobenzene are collected.

At about 150 C 400 g of isopropanol are allowed to run into the brown solution and the mixture is cooled to room temperature.

The crystal sludge is filtered off, washed with isopropanol and dried in a vacuum drying cabinet. The yield of di-benzoxazolyl-furane is 93.7 percent of theory. Melting point 246 C.

EXAMPLE 15 1,2-Di-[benzoxazolyl-( 2 ]-ethane A mixture of 220 g of 1-hydroxy-2-aminobenzene, 118 g of succinic acid, 600 g of trichlorobenzene, 5 g of boric acid, and 3 g of piperidine is heated to 210 C over the course of 4 hours with exclusion of air, and the temperature is raised to 220 C over the course of a further hour.

The mixture is stirred for 2 hours at 220 to 225 C and 400 g of isopropanol are carefully added at about 150 C.

The product is filtered off at room temperature, washed with isopropanol and dried in a vacuum drying cabinet. The yield of di-benzoxazolyl-ethane is 97.3 percent of theory. Melting point l92.7 to 193 C.

EXAMPLE l6 A mixture of 166 g of terephthalic acid, 220 g of l-hydroxy- Z-aminobenzene, 5 g of boric acid, 400 g of trichlorobenzene and 3 g of piperidine is heated to 210 C over the course of 4 hours. The greenish suspension is heated to 215 C over the course of a further hour, whereby a thick brown sludge is produced. Finally the mixture is stirred for 2 hours at 215 C. 400 g of isopropanol are allowed to run in at 150 C. The product is filtered off at room temperature, washed with isopropanol and dried in vacuo.

The yield is 318 g or 95.4 percent of theory. Melting point 340 C.

EXAMPLE l7 2,5-Di-[benzoxazolyl-(2')]-thiophene A mixture of 219 g of l-hydroxy-2-aminobenzene, 172 g of 2,S-thiophenedicarboxylic acid, 600 g of trichlorobenzene, 6 g of boric acid and 3 g of N-methylpyrrolidine is heated to 220 C over the course of 5 hours with exclusion of air and is stirred for 3 hours at this temperature. A golden brown solution is obtained, into which 400 g of isopropanol are allowed to run carefully at about 150 C. The product is filtered off at room temperature and carefully washed with isopropanol.

The yellow crystals are dried in a vacuum drying cabinet at to C.

The di-benzoxazolyl-thiophene is obtained in a yield of 308.4 g or 96.9 percent of theory. Melting point 220 C.

EXAMPLE l8 2,5-Di-[benzoxazolyl-(Z')]-thiophene A mixture of 219 g of l-hydroxy-2-aminobenzene, 172 g of 2,5-thiophenecarboxylic acid, 6 g of boric acid, 600 g of trichlorobenzene and 1.5 g of diethylenetriamine is heated in the reaction vessel, with exclusion of air, to 220 C over the course of 5 hours and is finally stirred for 3 hours at 220 C.

Four hundred grams of isopropanol are carefully allowed to run in at about 150 C, and the crystal sludge is filtered off on a porcelain suction filter at room temperature and washed with isopropanol.

The desired product is obtained in a yield of 300 g or 94.5 percent of theory. Melting point 219 to 2 l 9.4 C.

EXAMPLE l9 2,5-Di-[benzoxazolyl-(2')]-thiophene A mixture of 220 g of l-hydroxy-2-aminobenzene, 172 g of 2,S-thiophenedicarboxylic acid, 600 g of trichlorobenzene, 6 g of boric acid and 1.5 g of 1,4-diaza-bicylco[2,2,2]-octane is heated to 220 C over the course of 5 hours with exclusion of air. The mixture is stirred for 3 hours at 220 to 222 C, isopropanol is added at C, and the product filtered off at room temperature. The yellow crystals are rinsed with isopropanol and dried.

The dibenzoxazolyl-thiophene is obtained in a yield of 305.9 g or 96.2 percent of theory. Melting point: 219.2 to 219.6 C.

EXAMPLE 20 2,5 -Di-[ benzoxazolyl-( 2 ]-thiophene a. 219 g of l-hydroxy-2-aminobenzene, 172 g of 2,5- thiophenedicarboxylic acid, 600 g of 1,2,4-trichlorobenzene, 6 g of boric acid and 2 g of pyrrolidine are heated to 210 C over the course of 4 hours, with exclusion of air. The mixture is heated to 220 C over the course of a further hour and is kept at this temperature for 3% hours.

Four hundred grams of isopropanol are carefully allowed to run in at C, whereupon the reaction product separates out as crystals. After filtering, washing and drying, the di- (benzoxazolyl)-thiophene is obtained in the form of light yellow crystals in a yield of 304.8 g, corresponding to 96 percent of theory. Melting point: 2 l 9. 8 to 220.2 C.

b. 1f instead of pyrrolidine the same amount of cyclohexylamine is employed, the reaction product is obtained in a yield of 305.4 g.

c. instead of the pyrrolidine, 2 g of diisopropylamine are employed as the nitrogen base and in other respects the procedure described above is followed. The reaction product is obtained in a yield of 307.4 g (96.7 percent of theory). Pale yellow crystals of melting point 220.5 to 221 C.

EXAMPLE 21 2,5-Di-[benzoxazolyl-( 2')]-thiophene a. A mixture of2l9 g of 1-hydroxy-2-aminobenzene, 172 g of 2,5thiophenedicarboxylic acid, 600 of trichlorobenzene, 6 g of boric acid and 2 g of aminoguanidine bicarbonate is heated to 220 C over the course of 4 hours with exclusion of air and stirred for 4 hours at this temperature. 400 g of methanol are carefully allowed to run in at 100 C and the product is filtered off at room temperature, washed with methanol and dried in a vacuum drying cabinet. Yield: 305 g of pale yellow crystals of melting point 221 C.

b. If, instead of aminoguanidine bicarbonate, half the amount l g) of guanidine acetate is employed, the reaction product is obtained in a yield of 97.8 percent of theory.

EXAMPLE 22 2,5-Di-[benzoxazolyl-(2)]-thi0phene A mixture of 219 g of 1-hydroxy-2-aminobenzene, 172 g of 2,5-thiophenedicarboxylic acid, 600 g of trichlorobenzene, 6 g of boric acid and 2 g of diethylamine is heated to 220 C over the course of 4 hours with complete exclusion of air and is kept at this temperature for 4 hours. In the course thereof a mixture of diethylamine, water and trichlorobenzene distils off.

Four hundred grams of isopropanol are carefully allowed to run into the brown solution at 150 C and the mixture is cooled to room temperature. The crystals are filtered off, washed with isopropanol and dried in a vacuum drying cabinet.

The di-(benzoxazolyl)-thiophene is obtained in the form of light yellow crystals in a yield of 308.1 g or 97.1 percent of theory. Melting point: 222 C.

EXAMPLE 23 2,5-Di-[benzoxazolyl-(2)]-thiophene a. A mixture of 219 g of l-hydroxy-2-aminobenzene, 172 g of 2,S-thiophenedicarboxylic acid, 600 g of trichlorobenzene, 6 g of boric acid and 2 g of dimethylamine hydrochloride is heated with exclusion of air as described in the preceding example and is stirred for 4 hours at 220 C. The batch is mixed with 400 g of isopropanol, and the crystals are filtered off at room temperature and washed with isopropanol.

Di-(benzoxazolyl)-thiophene is obtained in a yield of 305.1 g or 96.0 percent of theory. Melting point: 221 C. b. If instead of dimethylamine hydrochloride 2 g of methylamine hydrochloride are employed, the reaction product is obtained in a yield of 301.3 g.

EXAMPLE 24 Manufacture of l,4-di[benzoxazolyl-(2')]-naphthalene A mixture of 6.5 g (0.03 mol) of 1,4-naphthalenedicarboxylic acid, 6.87 g (0.063 mol) of o-aminophenol, 0.18 g of boric acid, ml of distilled trichlorobenzene and 0.06 g of piperidine is heated over the course of 90 minutes to 160 C in a sulphonation flask having a water separator, under a nitrogen atmosphere. The temperature is raised to 220 over the course of a further 2 hours, with slight distillation starting from about 180 C onwards and a clear solution forming at 205 C. This solution is stirred for 3 hours at 220 to 225 C, in the course of which 1.6 ml of aqueous phase and 3.4 ml of trichlorobenzene distil. Thereafter the solution is cooled to 100 C and diluted with ml of isopropanol. The product which separates off is filtered off at room temperature, twice rinsed with 30 ml of isopropanol at a time and dried at 90 C under a waterpump vacuum. Crude yield: 10.3 g 94.9 percent of theory of beige felted small needles; melting point: 211 to 211.5 C. After recrystallization from 200 ml of distilled methylcellosolve, 10.0 g of pure yield (yellow needles), corresponding to 92.2 percent of theory, of melting point 21 1.5 to 212.5 C are obtained.

EXAMPLE 25 10.8 g of naphthalene-2,6-dicarboxylic acid,'18.5 g of 3- hydroxy-4-aminodiphenyl, 0.1 g of piperidine, 0.3 g of boric acid and 100 ml of a mixture of 73 percent of diphenyl-ether and 27 percent of diphenyl are stirred with exclusion of air and heated to 240 C over the course of4 hours. 0.5 g of boric acid anhydride are added to the light brown suspension which is heated to 255 C and stirred for one hour at 255 to 260 C. The mixture is allowed to cool, 50 ml of dichlorobenzene are added at 160 C and 100 ml of ethanol at C, and the product which has crystallised out is filtered off and washed with dimethylformamide until the filtrate issues colorless. Thereafter the product is further washed with 300 ml of2 percent strength sodium hydroxide solution, then with water until the filtrate reacts neutral, and dried in vacuo at 80 to C.

Yield: 14.7 g, corresponding to 57 percent of theory, of the crude compound of formula in the form of a yellow crystal powder of melting point 319 to 320 C. Recrystallisation from 600 ml of o-dichlorobenzene with the aid of Fullers earth yields 12.6 g (49 percent of theory) of light yellow glistening platelets of melting point 32lto 322 C.

A comparison experiment without piperidine gave a pure yield of2 l .4 percent. Melting point: 322.5 to 323.5 C.

I claim:

1. In a process for the manufacture of an aryloxazole comprising the reaction of a carboxylic acid selected from the group consisting of i. a dicarboxylic acid of benzene, naphthalene, stilbene,

thiophene or furane,

ii. a monocarboxylic acid of benzene or diphenyl, and

iii. an aliphatic dicarboxylic acid having a carbon chain of four carbon atoms, with an approximate equivalent amount of a hydroxyarylamino compound ofthe formula wherein R denotes the phenyl group or a residue (C,, H and occupies positions 4 or 5, and n represents a number from 1 to 5, in the presence ofa halogenobenzene, an alkylbenzene, a partially hydrogenated naphthalene or chlorinated naphthalene which is liquid at room temperature and boils at not less than 200 C, diphenylether or diphenyl, and in the presence of small amounts of boric acid, by first heating the reaction mixture to temperatures of at least C and then, with gradual increase in temperature, to temperatures of at least 200 C, wherein the improvement comprises carrying out said reaction in the presence of a nitrogen base selected from the group consisting of a. a secondary or tertiary, cyclic, non-aromatic nitrogen base containing one to two rings with five to eight ring members and one to two ring nitrogen atoms, and

b. a primary or secondary, aliphatic or cycloaliphatic amine with one to 12 carbon atoms and one to three amino groups.

2. Process according to claim 1 wherein in that the reaction is carried out in the presence of a secondary or tertiary piperidine or piperazine.

3. Process according to claim 1 wherein, as the carboxylic acid component, a carboxylic acid, containing one to two carboxyl groups, of benzene, diphenyl, naphthalene, stilbene,

styrene, thiophene or furane, or the analogues of these carboxylic acids containing one to three alkyl groups with one to four carbon atoms each, or an aliphatic dicarboxylic acid containing four carbon atoms, is reacted in approximately equivalent amount with an o-hydroxyaminophenol which can optionally be substituted by one to three alkyl groups with one to 18 carbon atoms, an alkoxy group with one to four carbon atoms, a carbalkoxy group with one to 12 carbon atoms, a halogen atom or a phenyl group.

4. Process according to claim 1, wherein a dicarboxylic acid of benzene, diphenyl, naphthalene, stilbene, thiophene or furane is reacted in approximately equivalent amount with. a ohydroxyaminobenzene which can optionally be substituted by one to three alkyl groups with one to four carbon atoms or by a phenyl group.

5. Process according to claim 1, wherein in that an ohydroxyamino benzene of formula wherein n denotes an integer having a value of at most 5, is used as the hydroxyaminoaryl compound.

6. Process according to claim 1 wherein the condensation is carried out in a trichlorobenzene, diphenyl-ether or diphenyl.

7. Process according to claim 1, wherein the condensation is carried out in the presence of 0.5 to 10 percent by weight of boric acid calculated relative to the sum of the amount by weight of the condensation components.

8. Process according to claim 1 wherein the reaction is effected by heating in a first stage to temperatures of to 200 C and in a second stage to temperatures of 200 to 260 C.

9. Process according to claim 1 wherein the reaction is carried out in the presence of an amylphenol.

Claims (8)

1. 2. Process according to claim 1 wherein in that the reaction is carried out in the presence of a secondary or tertiary piperidine or piperazine.
2. 3. Process according to claim 1 wherein, as the carboxylic acid component, a carboxylic acid, containing one to two carboxyl groups, of benzene, diphenyl, naphthalene, stilbene, styrene, thiophene or furane, or the analogues of these carboxylic acids containing one to three alkyl groups with one to four carbon atoms each, or an aliphatic dicarboxylic acid containing four carbon atoms, is reacted in approximately equivalent amount with an o-hydroxyaminophenol which can optionally be substituted by one to three alkyl groups with one to 18 carbon atoms, an alkoxy group with one to four carbon atoms, a carbalkoxy group with one to 12 carbon atoms, a halogen atom or a phenyl group.
3. 4. Process according to claim 1, wherein a dicarboxylic acid of benzene, diphenyl, naphthalene, stilbene, thiophene or furane is reacted in approximately equivalent amount with a o-hydroxyaminobenzene which can optionally be substituted by one to three alkyl groups with one to four carbon atoms or by a phenyl group.
4. 5. Process according to claim 1, wherein in that an o-hydroxyamino benzene of formula wherein n denotes an integer having a value of at most 5, is used as the hydroxyaminoaryl compound.
5. 6. Process according to claim 1 wherein the condensation is carried out in a trichlorobenzene, diphenyl-ether or diphenyl.
6. 7. Process according to claim 1, wherein the condensation is carried out in the presence of 0.5 to 10 percent by weight of boric acid calculated relative to the sum of the amount by weight of the condensation components.
7. 8. Process according to claim 1 wherein the reaction is effected by heating in a first stage to temperatures of 150* to 200* C and in a second stage to temperatures of 200* to 260* C.
8. 9. Process according to claim 1 wherein the reaction is carried out in the presence of an amylphenol.