DE1949334A1 - Process for the preparation of aryloxazoles - Google Patents

Description

CIBA AKTIENGESELLSCHAFT, BASEL (SWITZERLAND)

Case 6573 / E

Germany

Process for the preparation of aryloxazoles.

It is known that aryloxazoles, i.e. oxazoles, whose two neighboring carbon staffatorae of the oxazole ring are at the same time Ring members of an aromatic-carbocyelic six-membered ring are, suitably from ο-hydroxy-aminoaryl-Verblndun ·

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genes and carboxylic acids. Here are each an ο-hydroxyamino group and carboxylic acid group split off a total of 2 molecules of water, for example in the simplest Trap according to the scheme

Ii "f xiuwu ν s

It has now become a particularly advantageous and economical process for the preparation of aryloxazoles by reacting ο-hydroxyaminoaryl compounds with aliphatic, dicarboxylic acids containing at least 4 carbon atoms or 1 to 2 carbocyclic or heterocyclic rings each with 5 to 6 ring members containing mono- or dicarboxylic acids in the presence of one of the reactants chemically inert solvent found. This process is characterized in that the implementation the reactant in the presence of substoichiometric amounts of a nitrogen base from the group of

a) secondary or tertiary, cyclic, non-aromatic nitrogen bases, or

t?) the primary or secondary aminobenzenes, or

c) the primary or secondary, aliphatic or cycloaliphatic amines, or

d) basic nitrogen compounds that are at least once the atom grouping of the formula

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contain,

as well as in the presence of small amounts of boric acid is carried out by first bringing the reaction mixture to temperatures of at least 150 C and then with a gradual increase in temperature is heated to temperatures of at least 200 C. The specifications of a minimum temperature of 150 C for the first reaction stage means, of course, a temperature in the range between 150 and about 200 C, while the upper "limit for the temperature range from 200 C upwards is given by the beginning decomposition of the reaction partners and products.

One embodiment of this process is that the reaction of the reactants in the presence Substoichiometric amounts of a nitrogen base from the Group of

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,

and small amounts of boric acid is carried out by first bringing the reaction mixture to temperatures of at least 150 C and then gradually increasing to temperature

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doors is heated to at least 200 C.

As can be seen from the reaction conditions defined above, one of the essential Features of this process are the use of selected nitrogen bases, while another criterion is the use of selected nitrogen bases associated application of sub-stoichiometric amounts of these Is nitrogen bases. In general, come after this Amounts of nitrogen base into account that are approximately between 0.05 and 20, preferably 0.5 to 10 percent by weight, based on the aminophenol to be used. Ground in practice however, normally much smaller amounts of nitrogen base are used, since the same is apparently a catalytic one Effect. Although larger amounts within the aforementioned limits have no adverse effect on the Reaction sequence, they are usually superfluous and uneconomical. Especially with the preferred to using nitrogen bases with a pK value of at least 7 amounts of 0.2 to 2 percent by weight (based on aminophenol) are completely sufficient. Pure practice is it is interesting to carry out the above-defined reaction in the presence of such nitrogen bases that belong to the group of

a) secondary or tertiary, cyclic, non-aromatic, 5- or 8-membered, 1 to 2 ring nitrogen nitrogen bases containing atoms off, or the

b) primary or secondary aminobenzenes, or the

c) primary or secondary aliphatic amines with

1 to 12 carbon atoms and 1 to 3 amino functions

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-5- 194933 «

belong. For achieving particularly favorable yield results it has proven to be very advantageous to use nitrogen bases of the defined type, which one pK value of at least 7 (measured in ethylene glycol monomethyl ether / water) exhibit.

Taking into account the production of connections with technical interest and more expedient Embodiment is to define the particularly preferred method in such a way that hereinafter

l) a carboxylic acid from the series

(i) Dicarboxylic acids of benzene, naphthalene, rods, Thiophen or furans,

(ii) monocarboxylic acids of benzene or diphenyls, or

(iii) the aliphatic dicarboxylic acids with a

Carbon atom chain of 4 carbon atoms,

with 2) a hydroxyarylamino compound of the formula

HO
(D

H ₂ IT

where R is the phenyl group or a radical - (

means and occupies positions 4 or 5, and η represents an integer from 1 to 5, in the presence

3) a nitrogen base with a pK value of at least 7 from the series of

(x) secondary or tertiary, cyclic, non-aromatic, 1 to 2 rings with 5 or 6 ring members and 1 to 2 Ringstiokatoffatome-

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holding nitrogen bases,

(xx) primary or secondary aliphatic or cycloaliphatic amines having 1 to 12 carbon atoms and 1 to 3 amino functions or

(xxx) guanidines

is implemented, this implementation being lower in the presence Amounts of boric acid is made by the reaction mixture first to temperatures of at least 150 C and then is heated to temperatures of at least 200 ° C with a gradual increase in temperature.

To further explain the bases to be used, it should be noted that under secondary or tertiary, cyclic non-aromatic nitrogen bases such compounds are to be understood whose secondary or tertiary nitrogen atoms are present as ring members. In general exhibit these non-aromatic nitrogen heterocycles 6 ring links, but 5> can also be used Compounds containing 7 and 8 ring members (e.g. bicyclic types) are used. Furthermore, it is usually to compounds with 1 to 2 ring nitrogen atoms. Typical representatives for 5-membered nitrogen bases of this type are e.g. pyrrolidine, pyrazolidine, imidazolidine and its N-alkyl derivatives, for 6-membered nitrogen bases the piperidines and piperazines and their N-alkyl derivatives, furthermore

009 * 16/18271

Morpholine types. Among the higher cyclic nitrogen bases, the bicyclic types such as tetrahydroquinoline or bicyclic endo-alkyl types such as quinuclidine and 1,4-diazabicyclo- [2 _i 2 _i 2] -octane are to be mentioned as examples.

Primary and secondary aminobenzenes can in principle be used, although they are mostly low because of their low value pK value give lower yields. They are made by bases like aniline, toluidines, xylidines, and phenylenediamines their N-alkyl derivatives and analogously constructed compounds. In general, these are mono- or diamines.

In the case of the primary or secondary aliphatic amines, alkylamines (straight-chain or branched) with 1 to 12 carbon atoms and 1 to 3 amino groups of a primary or secondary nature. Furthermore however, polyalkylenepolyamines (e.g. diethylenetriamine, triethylenetetramine) are also readily aliphatic Amines with hydroxyl groups (e.g. diethanolamine) or alkoxy groups or those amines that, in addition to the mandatory primary or secondary amino groups, in addition, tertiary amino groups (dialkylaminoalkylamines) are suitable. Cycloaliphatic amines are to be understood here as meaning those whose amino group is attached to a cycloaliphatic Ring bonded (e.g. cyclohexylamine).

For the group of nitrogen bases with the structural element in question

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N N

let melamine, guanidine, Called dicyandiamide and biguanide.

Examples of advantageously usable amines are (pK value given in brackets): Piperidine (9.72), N-methylpiperidine, N-oxethylpiperidine, Pyrrolidone (9.82), N-methylpyrrolidone, N-methylpiperazine (9 * Ν, Ν-Dlmethylpiperazin, N-Oxäthylpiperazin, N-Aminoathylpi ^ srazln, 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-KCT (6.4l), Diethylenetriamine (9 * 52), guanidine acetate, aminoguanidine «HC0, Diphenylguanidine (7.66), diazabicyclo- [2.2.2] octane, Tetrahydroquinoline.

The reaction according to the present process takes place in two stages, ie condensation to the acyl compound takes place primarily and a ring closure reaction takes place in the second stage. Demgemäßs is the brought fteäktionsgemisch first heated to temperatures of at least 150 ° C to about 200 C until hereinafter (3e on the nature of the reactants after a certain residence time) under a slow temperature increase to ate necessary for the Ringschlussreaktlon minimum temperature of about 200 ° .G. The practical working range for the ring-closing reaction stage is 200 to 260 ^ö C, JE

e / tear

however, if the components are sufficiently thermally stable, 260 ° C. can definitely be exceeded.

If aliphatic carboxylic acids are used as starting materials in the process described above, they contain two carboxylic acid groups and at least four carbon atoms. The bridge member between the two carboxylic acid groups may be a branched or unbranched _s a saturated or unsaturated aliphatic hydrocarbon radical. This radical can, however, also contain substituents, for example halogen atoms such as chlorine, amino groups, alkoxy groups such as methoxy and, in particular, hydroxyl groups. Examples of aliphatic dicarboxylic acids are adipic acid, dichlorosuccinic acid, tartaric acid, aspartic acid, thiomalic acid, but in particular succinic acid, fumaric acid and malic acid. It should be noted that, under certain circumstances, when carrying out the present process, changes can also occur in the bridge between the two carboxylic acid groups, for example splitting off another molecule of water from tartaric acid and malic acid or ammonia from aspartic acid, with carbon-carbon double bonds being formed.

The method according to the invention is particularly valuable for the conversion of cyclic-aromatic carboxylic acids. In this case, the ring systems can have one or two carboxylic acid groups and two or preferably one oarbo-

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contain cyclic or heterocyclic ring. Carbocyclic Rings are aromatic, as is the case with naphthalene, diphenyl, and benzene-mbno and dicarboxylic acids. Heterocyclic rings preferably contain five ring members, namely 4 carbon atoms and one oxygen or Sulfur atom. So there are especially monocycli- '; consider benzene, furan or thiophenecarboxylic acids. The heterocyclic ones and especially the aromatic carbocyclic ones Rings can in addition to the carboxylic acid groups contain further substituents, e.g. halogen atoms such as bromine or chlorine, alkyl groups with 1 to 4 carbon atoms such as methyl, ethyl, isopropyl, tertiary butyl, alkoxy groups with 1 to 2 carbon atoms.

A preferred embodiment of the present invention is that a carboxylic acid component, which contains a 1 to 2 carboxyl group-containing carboxylic acid of benzene, diphenyl, naphthalene, stilbene, of styrene, thiophenes or furan, or the 1 to 3 alkyl groups each containing 1 to 4 carbon atoms Analogs of these carboxylic acids or a 4 carbon represents atoms containing aliphatic dicarboxylic acid, in approximately equivalent amount with an ο-hydroxyaminophenol is reacted, which optionally with 1 to 3 alkyl groups having 1 to 18 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a carbalkoxy group

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194933A

may be substituted with 1 to 12 carbon atoms, a halogen atom or a phenyl group.

The implementation of approximately equivalent amounts of a dicarboxylic acid is of technical and practical interest of benzene, diphenyls, naphthalene, stilbene, of the thiophene or furan with an o-hydroxyaminobenzene, which optionally with 1 to 3 alkyl groups with 1 to Carbon atoms or a phenyl group may be substituted.

Examples of the starting materials which can be considered as aromatic-eyclic carboxylic acids are i
Naphthalene-1- or -2-carboxylic acid, naphthalene-1,4- or

-1,5-dicarboxylic acid, diphenyl-4,4'-dicarboxylic acid, stilbene-4,4'-dicarboxylic acid, Cinnamic acid, benzenecarboxylic acid, 3 ~ or preferably 4-methylbenzenecarboxylic acid, benzene-1,3- or preferably -1,4-dicarboxylic acid, furan-2-carboxylic acid, Thiophene-2-carboxylic acid, 3> ^ "- dimethylthiophene-2,5-diacid, 3i4-Dlphenylthiophene-2,5- <iicarboxylic acid, diphenyl-4-carboxylic acid, 5-phenyl-thiophene-2-carboxylic acid, furan-2,5-d i carbonic acid.

Particularly valuable results are obtained with the dicarboxylic acids of the formula

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HC GH

(2) Il Il

HOOC-CC-COOH
\ /

obtained, wherein X is an oxygen atom or a sulfur atom mean, i.e. with furan and thiophene-2,5-dicarboxylic acid, and it is known that the dicarboxylic acids made from these especially the thiophenedicarboxylic acid, and optionally further substituted ones Bisbenzoxazoles obtainable from o-Hydroxyaminobenzenes are valuable optical brighteners.

As further starting materials are the present "the Process Hydroxyaminoary! Compounds required that the Contain hydroxyl group and the (primary) amino group adjacent to each other. There are, for example, 1,2- or 2,1-hydroxyaminonaphthalenes or, preferably, o-Hydroxyaminobenzenes, which have 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 1,1,3,3-tetramethylbutyl, may also contain two methyl groups. Preferred are the o-hydroxyaminobenzene, none contains further substituents, and o-hydroxyaminobenzenes, which have one or two alkyl groups as further substituents, contain an alkoxy group, a halogen atom or a phenyl group. Of these, the o-hydroxyaminobenzenes are important of the formula (1) [see above], where in this formula the

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Phenyl group for R is preferably in position 5, while the group - (C 1H _2n-1 ) is preferably in position 4, ie predominantly hydroxyaminobenzenes of the formulas

HO Cl il ^H 2n-i ^: and ) (Ib) HO (la) \ T / Ä * H ₂ N HN

in use.

The implementation according to the present process takes place in a diluent, which as such in the Temperatures of the whole process must be liquid and does not take part in the reaction. But it is by no means there it is necessary that all products occurring during the implementation, i.e. the reaction r participants, intermediate stages and final substances are largely or even completely dissolved. In particular, those in the Carboxamides which form as intermediates are generally difficult to practically insoluble in such a diluent without this having an adverse effect. As the diluent should also be present at the high temperature at the end of the reaction process, it is advisable to to use such an inert organic solvent to dilute the reaction mixture, which under normal

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19A9334

pressure has a boiling point of at least 200 C. It is also possible ^ at the beginning of the conversions a at thinner or solvent boiling at lower temperatures apply, let this distill off and replace it in time with a higher boiling one, whereby even water is useful as a first diluent; For economic reasons alone, however, it is in Usually indicated from the start with a high-boiling diluent that cannot be replaced or renewed need to work. Examples of particularly suitable solvents are tetrahydronaphthalene and mixtures of diphenyl and diphenyl ethers and, in particular, trichlorobenzenes, although trichlorobenzene mixtures, as are commercially available can be used. The reaction is then preferably carried out in the presence a diluent carried out, which is liquid at room temperature and boiling at at least 200 ° C Halobenzene, preferably a trichlorobenzene, alkylbenzene, halogenated alkylbenzene, partially hydrogenated naphthalene, chlorinated naphthalene, furthermore diphenyl ether or diphenyl represents.

Equivalent amounts of the two starting materials from which the oxazoles are formed by dehydration are expediently used, i.e. one mole of monocarboxylic acid to one mole of hydroxyaminoaryl compound and one mole of dicarboxylic acid.

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acidic acid to two moles of hydroxyaminoaryl compound, or by at most 5 mole percent to one side or the other different quantities. The amount of the diluent is to be calculated so that the reaction mixture also with Insoluble products, in particular the carboxamides formed as intermediates, occur without difficulty Agitators of conventional design can be kept homogeneous. Depending on the choice of starting materials, the particularly advantageous amounts of diluent result in differences. In general, good results are obtained when about half to twice the amount of the two starting materials are applied to diluent will.

The dehydration catalyst is used in the usual amounts, i.e. about 0.5 to 10 $ boric acid Calculated by weight of the condensation components.

Favorable results are achieved if you first put the nitrogen base and the carboxylic acid on top of one another can act. So, for example, the base and the carboxylic acid can first be mixed with one another in the diluent stir together the hydroxyaminoaryl compound and the dehydration catalyst add and then slowly continue heating until the acid amide is formed first and then at higher temperature the ring closure takes place.

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A simpler and particularly advantageous procedure is to use a mixture that is obtained by combining the nitrogen base with a carboxylic acid of the specified composition and a Hydroxyaminoary! compound of the specified Composition obtained in a liquid diluent, first at temperatures from 150 to Heated to 200 C until a hydroxyaminoary compound per molecule about one molecule of water is split off, and then by heating to even higher temperatures, up to about 260 C the Conversion ended, the water being continuously removed by distillation.

To avoid unwanted oxidation, it is advisable to keep the reaction medium in contact with oxygen to avoid, i.e. to work with exclusion of air, expediently under nitrogen. It has proven to be particularly advantageous the addition of antioxidants such as amylphenol has been proven. This not only increases the yield, but also strongly suppresses the formation of by-products, which act as fluorescence quenchers, i.e. increase the purity of the end products.

As can be seen from the preceding statements, in the present method in the first Stage the carboxamide and in the second the oxazole. Formed. In the minimum temperature at which the second stage

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"there may be differences from case to pail result within the specified limits. It is advisable to run the two reaction stages one after the other to leave, i.e. not to heat the mixture to the ring closure temperature from the outset before the Carboxamide has essentially formed.

According to the present process, the oxazoles are obtained in very good yield and purity.

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example 1

2 _J 5-Dl- [benzoxazolyl- (2 ^> ) j -thiophene.

600 g of trichlorobenzene (mixture of isomers), 219 S of 1-hydroxy-2-aminobenzene, 172 g of thiophene-2,5-dicarboxylic acid, 6 g of boric acid and 1 g of piperidine are stirred in the reaction vessel with the exclusion of air. The pale yellow suspension is heated to 220 ° C. within 4 hours, the color changes to yellow, and at 160 ° C. the distillation of the piperidine / water mixture begins. The temporarily thinning reaction mixture turns at 180 ° C into the thick, yellow crystal pulp of 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. A total of 140 to 260 ecm of distillate is obtained, with trichlorobenzene also distilling over from 180 ° C. After cooling to about 150 ^° C., the reaction product begins to separate out in crystalline form. 400 g of isopropanol are carefully added and the mixture is cooled to room temperature. The yellow crystals are filtered off with suction, washed with isopropanol and dried in a vacuum drying tank at 80 to 90 ° G.

The yield obtained is from 305 to 308 g of 2,5-di- [benzoxazolyl- (2 ¹ )] -thiophene, corresponding to 96 to 97 % of theory.

.Melting point; 221 to 222 ° C.

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194933 «

For additional purification, the product can be six times the amount of trichlorobenzene, treated at ⁰ C with an adsorbent I5O, clarified by filtration and concentrated.

The pale yellow crystals, whose melting point is 223 ° C., are completed by adding isopropanol failed.

If 5 g of piperidine are used instead of 1 g of piperidine, the desired product is obtained in a yield of 9 ^ * 8 % of theory.

If the experiment is carried out with an addition of only 0.2 g of piperidine, the yield is 93 * 5 % of the

Theory.
Melting point: 222 ° C

Example 2

2,5-Ρΐ- [ρ6ηζοχ8 · ζο1ν1- (2 ') 3-thiophene.

A mixture of 600 g trichlorobenzene, 219 g 2-aminophenol, 172 g 2,5-thiophenedicarboxylic acid, 6 g boric acid, 5 g N-methyl

and 5 g of amy phenol
piperidinV is heated to 220 ° C within 4 hours with exclusion of air. A golden brown solution is obtained and. a mixture of methylpiperidine / water / trichlorobenzene distilled off. Finally, the mixture is stirred for 3 hours at 220 to 222 ° C.

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• ■

• I ·
■ ι

In I50 ⁰ C is allowed to gently run 400 g of isopropanol. It is cooled to room temperature and then washed with isopropanol. The 2,5-di- [benzoxazolyl- (2 ')] -thiophene is obtained in the form of yellow crystals in a yield of 97 % of theory.
The melting point is 221 to 222 ° C.

If 20 g of N-methylpiperidine are used instead of the above-mentioned amount of the piperidine derivative, the yield is 96.3 %> if only 1 g of N-methylpiperidine is used, a yield of 95 % is achieved.

Example 3

2,5-di- [benzoxazolyl- (2 ^t )] -thiophene.

A mixture of 6OO g trichlorobenzene, 219 g o-aminophenol, 172 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of morpholine is heated to 220 ° C within 4 hours with complete exclusion of air. Then stir one for 3 hours at 220 to 222 ° C and receives a golden brown Solution.

In I5O ⁰ C to 400 g of isopropanol is run in, cooled to room temperature, filtered off and washed with isopropanol. The 2,5-di- [benzoxazolyl- (2 ')] -thiophene is obtained in a yield of 303 g or 95 * 3 % of theory. Pure yellow crystals from SohmelzDunkt 221 ° C.

ΌαΓΤ816 / 1827

Example 4

2,5-di- [benzoxazolyl- (2 ')] thiophene.

A mixture of 600 g trichlorobenzene, 219 ß o-aniinophenol, 172 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 S Ν, Ν'-Dimethylpiperazine is heated to 220 ° C within 4 hours heated, working with absolute exclusion of air will. A golden brown solution is obtained and from 160 ° C. a mixture of dimethylpiperazine / water / trichlorobenzene is distilled away. The mixture is then stirred for a further 3 hours at 220 to 222 ° C. 400 g of isopropanol are left at about 150 ° C. run towards. It is cooled to room temperature, filtered off with suction and washed with isopropanol.

The di- [benzoxazolyl- (2 ')] -thlophen is obtained in a yield of 305.7 g, corresponding to 96 % of theory. The yellow crystals melt at 221 ° C.

If 2.5 g of N-methylpiperazine are used instead of dimethylpiperazine, the reaction product is obtained in a yield of 95 * 2 %,

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7949334

Example 5

' 2,5-di- [benzoxazolyl- (2') j-thiophene.

A mixture of 600 g of trichlorobenzene, 219 S o-aminophenol, 172 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 & oxyaethylpiperazine is heated to 210 ° C. in the course of 3 hours and to 220 ° C. in a further hour. After a temporary separation of the yellow diamide compound, a brown solution forms. The mixture is stirred for 3 hours at 220 to 222 ° C. At 150 ° C., 400 g of isopropanol are carefully run in, the crystal slurry is cooled to room temperature and washed with isopropanol. The di-benzoxazolyl-mophen is obtained in a yield of 302 g. Melting point 221 to 221.4 ° C.

If the oxyethylpiperazine in the reaction mixture is replaced by the same amount of oxyethylpiperidine, the same reaction product is obtained in a yield of 305 g or 96 % of theory.

Example 6

2,5-di- [benzoxazolyl- (2 ') ethiophene.

The mixture of 600 g of trichlorobenzene, 220 g of 1-hydroxy-2-aminobenzene, 172 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 S ethylethanolamine is heated with the exclusion of air as in the previous examples.

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The 2,5-di ~ [benzoxazolyl- (2 ') 3-thiophene is obtained in a yield of 30 % or Qk, 6% of theory. Melting point 220 ° C.

If 3 S diethylamine is used as the amine additive, a yield of 95-3 % of theory is obtained.

Example 7

- (2 *) 3-thiophene.

With the exclusion of air, a mixture of 600 g of trichlorobenzene, 218 g of 1-hydroxy-2-aminobenzene, 173 * 5 S 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 g of piperazine according to Example 1 is heated and worked up. The yield is 295 g or 92.7 % of theory. If the aminoethylpiperazine is used instead of piperazine under the following approach:

600 g trichlorobenzene

220 g of 1-hydroxy-2-aminophenol

172 g of 2,5-thiophenedicarboxylic acid

6 g boric acid

3 g aminoethylpiperazine,

the abovementioned reaction product is thus obtained in a yield of 299 g or 9 ^ * 2 % of theory.

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J 24 -

Example 8

2,5-di- [benzoxazolyl- (2 ') 3-thiophene · A mixture of 600 g trichlorobenzene, 219 S 1-hydroxy-2-aminobenzene, 172 g 2,5-thiophenedicarboxylic acid, 6 g boric acid and 3 g ethylenediamine is according to Example 1 heated with exclusion of atmospheric oxygen.

Isopropanol is added, the crystal sludge is filtered off with suction at room temperature and washed with isopropanol.

The dibenzoxazolylthiophene is obtained in a yield of 91 * ² % of theory.
Melting point 28 ° C.

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

Example 9

2,5-di- [benzoxazolyl- (2 ^> )] thiophene.

If a mixture of 600 g of trichlorobenzene, 219 S l ^ -hydroxy-2-aminobenzene, 172 g of 2,5-thiophenedicarboxylic acid, 6 g of boric acid and 3 S aniline is used analogously to Example 1, the desired product is obtained in a yield of 90 * 1 of theory.
Melting point · 220 ⁰ C.

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If a 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 S N-methylaniline is reacted in the same way, a yield of 91 * is obtained 2 % of theory.
Melting point 220 ° C.

Example 10

2,5-di [benzoxazolyl (2 ')] thiophene.

The dibenzoxazolylthiophene is obtained by reacting according to the instructions in Example 1 of 600 g of trichlorobenzene, 218 g of l-hydroxy-2-aminobenzene, 173.5 g of 2,5-thiophenedicarboxylic acid, 5 g of boric acid and 3 g of tetrahydroquinoline in a yield of 89 * 5 % obtain. Melting point 220 ° C.

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Example 11-

2,5-Di - [- 5-tert- butylbenzoxazolyl ~ - (2 ')] -thiophene ._ A mixture of 2ββ gl »hydroxy-2-amino-4-tert-butylbenzene, 138.5 g 2,5- Thiophenedicarboxylic acid, β g of boric acid, 350 g of trichlorobenzene and 2 g of piperidine are heated to 210 ° G over the course of 4 hours with exclusion of air. The temperature is increased to 220 ° C. over a further hour and finally stirred for 3 hours at 220 to 222 ° C.

The mixture is left in the clear, brown reaction mixture slowly run in 3OO g of isopropanol at 120 ° C.

At room temperature, the crystal slurry is suctioned off, washed with a total of 900 g of isopropanol and im Vacuum drying cabinet dried.

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 % of theory. Melting point 199 to 200 ° C.

Example 12

2- (4'-methylphenyl) 5-tert-butylbenzoxazole.

A mixture of 2? 2 g p-toluic _s 330 g of 1-Hy droxy-2-amino-4-tert "-butyl benzene ₁ 10 g of boric acid, 150 g of trichlorobenzene and 3 g of piperidine exclusion stirred under complete air and within 4 hours heated to 2OC. At 150 ° C a mixture of water and begins

■ # 09816/1827

Within a further hour the temperature is increased to 220 ° C. and finally 2 hours at Stirring at 220 to 225 ° C. After cooling to 120 ° C., 200 g of isopropanol are allowed to run in.

It is cooled to 5 ° C. and the crystal pulp is suctioned off on the porcelain groove. The crystals are made with total 350 g of cold isopropanol washed.

The yield is 48l g or 90.6 % of theory. Melting point of the white, grayish crystals: 114 ° C.

If 3 g of N-methyl'pipe-ridin are used instead of the piperidine, a yield of 92.8 % of theory is obtained.

Example 13

4-benzoxazolyl (2) -diphenyl- (l, l ^l).

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

At 150 ° C., 400 g of isopropanol are carefully allowed to run in and cools to room temperature.

The crystal slurry is filtered off with suction and washed with isopropanol. The desired product is obtained in the form of almost colorless crystals in a yield of 229 6 · melting point 139.4 to 139 * 6 ° C. 009816/1827

Example l4

2,5-pi- [benzoxazolyl- (2 ')] furan.

A mixture of 220 g of l-hydroxy-2-aminobenzene, 156 g of 2,5-furandicarboxylic acid, 5 g of boric acid, 600 g of trichlorobenzene and 3 g of piperidine is heated to 210 ° C. in the course of 4 hours with the exclusion of air. At approx. At 1500 C a mixture of water and piperidine begins to distill away. Within a further hour, the temperature is increased to 220 ° C. and finally stirred For 2 hours at 220 to 225 ° C. There are a total of 135 ml of distillate with a portion of 65 ml of trichlorobenzene caught.

Beica. I5O ⁰ C is run in to 400 g of isopropanol to the brown solution and is cooled to room temperature.

The crystal slurry is filtered off with suction, washed with isopropanol and dried in a vacuum drying cabinet. The yield of di-benzoxazolyl-furan is 93 * 7 % of theory.
Melting point 246 ° C.

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Example 15

1,2-Di- [benzoxazolyl- (2 ') 3-ethane.

A mixture of 220 g of l-hydroxy-2-aminobenzene, Il8 g of succinic acid, 600 g of trichlorobenzene, 5 g of boric acid and 3 S piperidine heated to 210 ° C with the exclusion of air and the temperature within a increased to 220 ° C. for a further hour.

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

At room temperature it is filtered off with suction, washed with isopropanol and dried in a vacuum drying cabinet. The yield of di-benzoxazolylethane is 97 * 3 % of theory.
Melting point 192.7 to 193 ° C.

Example 16

1,4-di- [benzoxazolyl- (2 ^t ) 3-benzene "

A mixture of 166 g of terephthalic acid, 220 g of 1-hydroxy-2-aminobenzene, 5 g of boric acid, 400 g of trichlorobenzene and 3 g of piperidine is used within. 4 hours on Heated to 210 ° C. The greenish suspension is in a heated to 215 ° C. for a further hour, a thick brown paste being formed. Finally, the mixture is stirred during 2 hours at 215 ° C. At 150 ° C, 400 g of iso-

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run in propanol. It is suctioned off at room temperature , washed with isopropanol and dried in a vacuum.

The yield is 318 g or 95 # A % of theory, melting point 3 ^ 0 ° C.

Example 17

2,5-di- [benzoxazolyl- (2 ^> ) -3-thiophene.

A mixture of 219 S l-hydroxy-2-aminobenzene, 172 g of 2,5-thiophenedicarboxylic acid, 600 g of trichlorobenzene, 6 g of boric acid and 3 g of N-methylpyrrolidine is heated to 220 ° C. within 5 hours with the exclusion of air and 3 stirred for hours at that temperature, "a golden brown solution ,, to be at about ⁰ C I5O careful

g of isopropanol can be added. At room temperature is suctioned off and carefully washed with isopropanol.

The yellow crystals are dried at 80 to 90 ° C. in a vacuum drying cabinet.

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

Example l8.

2,5-di- [benzoxazo3.yl- (2 ¹ ) 3- thiophene.

A mixture of 219g I-hydroxy-2-aminobenzene, 1? 2 g 2,5 ~ thiophenecarboxylic acid, 6 g boric acid, 600 g trichlorobenzene and 1.5 g diethylenetriamine with exclusion of air within 5 hours Heated to 220 ° C and finally at 220 ° C for 3 hours touched.

At about 150 ° C., 400 g of iso- ■ are carefully left Propanol flow in, sucks the crystal sludge on a porcelain suction filter at room temperature and washes with isopropanol.

The desired product is obtained in a yield of 300 g or 94.5% of theory. Melting point 219 to 219.4 ° C.

Example 19

2,5-di- [benzoxazolyl- (2 ^l ) 3-thiophene » A mixture of 220 g of l-hydroxy-2-aminobenzene, 172 g of 2,5-thiophenedicarboxylic acid, 600 g of trichlorobenzene, 6 g of boric acid and 1.5 gl , 4-Diaza-bicyclo [2,2,2] -octane is heated to 220 ° C within 5 hours with exclusion of air. The mixture is stirred for 3 hours at 220 to 222 ° C., isopropanol is added at 140 ° C. and suction is carried out at room temperature

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away. The yellow crystals are washed out with isopropanol and dried.

The dibenzoxazolyl-thiophene is obtained in one Yield of 305 * 9 S or 96 * 2 $ of theory. Melting point: 219.2 to 219.6 ° C.

Example 20

2,5-di- [benzoxazolyl- (2 ') 3-thiophene.

a) 219 S l-hydroxy-2-aminobenzene, 172 g of 2,5-thiophenedicarboxylic acid, 600 g 1,2,4-trichlorobenzene, 6 g boric acid and 2 g of pyrrolidine are excluded from air within heated to 210 ° C. for 4 hours. In the course of a Another hour is heated to 220 C and held at this temperature for 3 1/2 hours.

At 150 ° C., 400 g of isopropanol are carefully run in, the reaction product separating out in crystalline form. After suctioning off, washing and drying, the di- (benzoxazolyl) thiophene is obtained in the form of pale yellow crystals in a yield of 304.8 g, corresponding to 6% of theory. , Melting point: 219.8 to 220.2 ° C-.

b) If the same amount of cyclohexylamine is used instead of pyrrolidine, the reaction product is obtained in a yield of 305 * 4 g

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c) Instead of the pyrrolidine, 2 g of diisopropylamine are used as nitrogen base and the procedure is otherwise as follows described above. The reaction product is obtained in a yield of 307.4 g (96.7% of theory). Pale yellow crystals with a melting point of 220.5 to 221 ° C.

Example 21

2,5-di- [benzoxazolyl- (2 ') j -thiophene.

a) a mixture of 219 g of 1-hydroxy-2-aminobenzene, 172 g of 2,5-thiophene-dicarboxylic acid, 600 g of trichlorobenzene, 6 g Boric acid and 2 g of aminoguanidine bicarbonate are extracted with exclusion of air heated to 220 C within 4 hours and stirred at this temperature for 4 hours. Man carefully lets 400 g of methanol flow in at 100 ° C., sucks off at room temperature, washed with methanol and dried in the vacuum drying cabinet.

Yield: 305 g of pale yellow crystals with a melting point of 221 ° C,

b) If half the amount (1 g) of guanidine acetate is used instead of aminoguanidine bicarbonate, this is obtained. Reaction product in a yield of $ 97.8 of theory.

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Example 22

2,5-di- [benzoxazolyl- (2 ^f ) 3-thiophene.

A mixture of 219 S 1-hydroxy-2-aminobenzene, 172 g of 2,5-thiophene-dicarboxylic acid, 600 g of trichlorobenzene, 6 g of boric acid and 2 g of diethylamine are used under perfect conditions Final air heated to 220 C within 4 hours and kept at this temperature for 4 hours. A mixture of diethylamine and water is distilled and trichlorobenzene gone.

The brown solution is carefully left at 150.degree 400 g of isopropanol run in and cool to room temperature. The crystals are filtered off with suction and washed with isopropanol and dries in the vacuum drying cabinet.

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

Example 23

2,5-di- [benzoxazolyl- (2 ') 3-thiophene.

a). A mixture of 219 S 1-hydroxy-2-aminobenzenes 172 g of 2,5-thiophene-dicarboxylic acid, 600 g of trichlorobenzene, 6 g

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Boric acid and 2 g of dimethylamine hydrochloride are described with exclusion of air as in the previous example heated and stirred at 220 C for 4 hours. It is mixed with 400 g of isopropanol, filtered off with suction at room temperature and the crystals are washed with isopropanol.

The di- (benzoxazolyl) thiophene is obtained in a yield of 305 * 1 g or 96 * 0% of theory. Melting point: 221 ° C.

b) If 2 g of methylamine hydrochloride are used instead of dimethylamine hydrochloride, the reaction product becomes obtained in a yield of 301 * 3 g.

Example 24

Preparation of 1,4-di- [benzoxazolyl- (2 ')] naphthalene.

In a suIfier flask with a water separator a mixture of 6.5 g (0.03 mol) 1,4-naphthalenedicarboxylic acid, 6.87 g (0.063 mole) o-aminophenol, 0.18 g boric acid, 15 ml least. Trichlorobenzene and 0.06 g piperidine under a nitrogen atmosphere heated to 160 ° C. within 90 minutes. During the temperature is increased to 220 ° C. for a further 2 hours Increased, with a weak distillation begins from about 180 ° C and a clear solution forms at 205 ° C. These

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The solution is stirred for 3 hours at 220 to 225 ° C., 1.6 ml of aqueous phase and 1.k ml of trichlorobenzene distilling. The solution is then cooled to 100 ° C. and diluted with 20 ml of isopropanol. The product which separates out is filtered off with suction at room temperature, washed twice with 30 ml of isopropanol each time and dried at 90 ° C. in a water jet vacuum. Raw yield: 10.3 g = $ 94.9 of theory, beige felty needles; Melting point: 211 to 211.5 ° C. After recrystallization from 200 ml of dist. Methylcellosolve 10.0 g of pure yield (yellow needles), corresponding to 92.2% of theory from a melting point of 211.5 to 212.5 ° C., are obtained.

Example 25

10.8 g naphthalene-2,6-dicarboxylic acid, 18.5 g 3-hydroxy ■ 4-aminodiphenyl, 0.1 g of piperidine, 0.3 g of boric acid and 100 ml of a mixture of 73 $ diphenyl ether and 27 $ diphenyl stirred in the absence of air and heated to 240 ° C. within 4 hours. 0.5 g is added to the light brown suspension Boric acid anhydride, heated to 255 C and stirred during one hour at 255 to 20 ° C. It is allowed to cool, gives

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Ιβθ ° C 50 ml dichlorobenzene and at 80 ° C 100 ml ethanol to, the product which has crystallized out is sucked off and washed with dimethylformamide until the piltrate is colorless. Then it is washed with 300 ml of 2% sodium hydroxide solution, then with water until the filtrate reacts neutrally and dries under vacuum at 80 to 85 C. Yield: 14.7 g, corresponding to $ 57 of the crude theory Compound of formula

in the form of a yellow crystalline powder with a melting point up to 320 ⁰ C. Recrystallization from 600 ml of ο-dichlorobenzene with the aid of bleaching earth results in 12.6 g (49 $ of theory) of light yellow, shiny flakes of melting point 321-322 ° C.

A comparison experiment without piperidine gave a pure yield of 21.4 #. Melting point: 322.5 to 323.5 ° C.

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Claims (1)

Claims 1. A process for the preparation of aryloxazoles by reacting ο-hydroxyamino-aryl compounds with aliphatic dicarboxylic acids containing at least k carbon atoms or 1 to 2 carbocyclic or heterocyclic rings each having 5 to 6 ring members containing mono- or dicarboxylic acids in the presence of one opposite the reactants chemically inert solvent, characterized in that the reaction of the .Reaktionspartner in the presence of sub-stoichiometric amounts of a nitrogen base from the group 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, or d) basic nitrogen compounds which have at least one atom grouping of the formula N N . contain, as well as in the presence of small amounts of boric acid is carried out by first bringing the reaction mixture to temperatures 009816/1827 of at least 150 C and then with a gradual increase in temperature is heated to temperatures of at least 200 C. 2. The method according to claim 1 for the preparation of aryl-oxazoles by reaction of o-hydroxyaminoaryl compounds with aliphatic dicarboxylic acids containing at least 4 carbon atoms or 1 to 2 carbocyclic acids or heterocyclic rings each with 5 to 6 ring members containing mono- or dicarboxylic acids in the presence of a chemically inert to the reactants Solvent, characterized in that the reaction of the reactants in the presence of substoichiometric Amounts of a nitrogen base from the group of a) secondary or tertiary, cyclic, non-aromatic Nitrogen bases, or b) the primary or secondary aminobenzenes, or c) the primary or secondary aliphatic or eyeloaliphatic amines, as well as small amounts of boric acid is carried out by the Reaktionsgemiseh is first heated to temperatures of at least 150 ⁰ C and then gradually increase to temperatures of at least 200 ° C. 3 · The method according to claim 1 or 2, characterized in that the reaction in the presence of a nitrogen 009816/1827 base from the group of a) secondary or tertiary, cyclic, non-aromatic, 5 to 8-membered, 1 to 2 ring nitrogen nitrogen bases containing atoms, or the b) primary or secondary aminobenzenes, · or the c) primary or secondary aliphatic amines, with 1 to 12 carbon atoms and 1 to 3 amino func- ψ functions is carried out. 4. The method according to any one of claims 1 to 3 characterized in that the reaction is carried out in the presence of a nitrogen base with a pK value of at least 7, measured in ethylene glycol monomethyl ether / water will. 5 · Method according to claim 1 for the production of> Aryloxazoles, characterized in that 1) a carboxylic acid from the series (i) Dicarboxylic acids of benzene, naphthalene,. Stilbene, thiophen or furans, (ii) monocarboxylic acids of benzene or diphenyls, or (iii) the aliphatic dicarboxylic acids with a carbon atom chain of 4 carbon atoms, with 2) a hydroxyarylamino compound of the formula 009816/1827 where R is the phenyl group or a radical - (C -Hp,) means and the positions 4 or 5 occupies and η a Represents number from 1 to 5 in the presence 3) a nitrogen base with a pK value of at least 7 from the series of (x) secondary or tertiary, cyclic, non-aromatic, 1 to 2 rings with 5 or 6 ring members and containing 1 to 2 ring nitrogen atoms Nitrogen bases, (xx) primary or secondary, aliphatic or cycloaliphatic amines having 1 to 12 carbon atoms and 1 to 3 amino functions, or (xxx) guanidines is implemented, this implementation being lower in the presence Amounts of boric acid is made by initially bringing the reaction mixture to temperatures of at least 150 ° C and then heated to temperatures of at least 200 ° C with a gradual increase in temperature. 6. The method according to claim 3 or 4, characterized in that the reaction is carried out in the presence of a secondary or tertiary piperidine or piperazine. 009816/1827 7. The method naoh one of claims 1 to 3 or 4, characterized in that the carboxylic acid component contains 1 to 2 carboxyl groups Carboxylic acid of benzene, diphenyls, naphthalene, stilbene, styrenes, thiophenes or furans, or the 1 to 3 alkyl groups, each containing 1 to 4 carbon atoms, of these carboxylic acids or analogues Aliphatic dicarboxylic acid containing 4 carbon atoms, in an approximately equivalent amount with an ο-hydroxyaminephenol is reacted, which optionally with 1 to 3 alkyl groups having 1 to 18 carbon atoms, one Alkoxy group having 1 to 4 carbon atoms, a carbalkoxy group having 1 to 12 carbon atoms, a halogen atom or a phenyl group. 8. The method according to any one of claims 1 to 3 * 6 or 7i characterized, that roughly equivalent Amount of a dicarboxylic acid of benzene, diphenyl, naphthalene, stilbene, thiophenes or furan with an o-hydroxyaminobenzene, which optionally has 1 to 3 alkyl groups with 1 to 4 carbon atoms or a phenyl group may be substituted will. 9. Method according to one of Claims 1 to 3 or 6 to 8, characterized in that the hydroxyaminoaryl compound is an o-hydroxyaminobenzene of the formula 009816/182 7 HO Kl ^H 2n-1> is used, where η is an integer with a value of at most 5 means. 10. The method according to any one of claims 1 to 9 * da- · characterized in that the condensation in a diluent is carried out, which is a liquid at room temperature and boiling at at least 200 C. Halobenzene, preferably a trichlorobenzene, alkylbenzene, halogenated alkylbenzene, partially hydrogenated naphthalene] chlorinated naphthalene, furthermore diphenyl ether or is diphenyl. 11. The method according to any one of claims 1 to 10, characterized in that the condensation in the presence from 0.5 to 10 percent by weight boric acid, calculated on the sum of the amount by weight of the condensation components, is carried out. 12. The method according to any one of claims 1 to 11, characterized in that the nitrogen base in amounts of 0.05 to 20 percent by weight, based on the amount by weight of aminophenol to be used, is used. 009816/18 2 7 13 · The method according to any one of claims 1 to 12, characterized characterized in that the reaction is carried out by heating in the first stage to temperatures from 150 to 200 C and in the second stage at temperatures from 200 to 2βθ C causes will. l4. Method according to one of Claims 1 to 13, characterized characterized in that the reaction is carried out in the presence of an antioxidant. 009816/1827