WO2020174058A1

WO2020174058A1 - Method for producing quinoxalines

Info

Publication number: WO2020174058A1
Application number: PCT/EP2020/055176
Authority: WO
Inventors: Miriam Margarethe UNTERLASS; Lukas P. LEUTGEB; Fabián Andrés AMAYA-GARCIA
Original assignee: Technische Universität Wien
Priority date: 2019-02-27
Filing date: 2020-02-27
Publication date: 2020-09-03
Also published as: KR20210134668A; AT522210B1; AT522210A1; EP3931184A1

Abstract

The invention relates to a method for producing quinoxalines by condensation of optionally substituted o-phenylenediamine with a diketone in accordance with the following reaction mechanism (mechanism 4) wherein: R₁, R₂ and R₃ each independently are hydrogen or a monovalent, saturated, unsaturated or aromatic hydrocarbon group with 1 to 20 carbon atoms, wherein one or more carbon atoms are optionally replaced with heteroatoms, which are each independently selected from O, N, S, F, CI and Br, and n is an integer from 0 to 4; wherein optionally two groups R₁ and/or the groups R₂ and R₃ are joined to one another and, together with the atoms to which they are bound, form a saturated, unsaturated or aromatic ring, and/or one R₁ each of two o-phenylenediamine molecules together stand for a chemical bond and hence form a diaminobenzidine; and wherein the condensation reaction is performed in water as a solvent by heating the reagents under pressure to a reaction temperature > 100°C.

Description

Manufacturing process for quinoxalines

The present invention relates to a new production process for quinoxalines. STATE OF THE ART

Compounds that carry the quinoxaline function are of enormous importance for a wide range of different areas of application. For example, they are of great interest as optoelectronic materials, antibiotics, herbicides, insecticides, cell stains and pharmaceuticals.

The majority of the known synthetic routes for quinoxalines are based on the condensation of o-phenylenediamines with 1,2-dicarbonyl compounds according to synthesis route "A" in reaction scheme 1 below (see, for example, "General Introduction to Quinoxaline Chemistry" in the Chemistry of Heterocyclic Compounds, Vol. 35, GWH Cheeseman and RF Cookson (Eds.), John Wiley & Sons, Ltd. (1979)).

Scheme 1

Not least because of the relative oxidation instability of o-phenylenediamine, which reacts rapidly to o-quinonediimine and then to 2,3-diaminophenazine in air even at room temperature, as shown in Scheme 2 below:

Scheme 2

There are also alternatives to the synthesis route "A" in which, instead of o-phenylenediamines, either o-nitrosoaminobenzenes or benzofuroxanes are used as the substrate, as in the synthesis routes "B" and "C" in reaction scheme 1 above is shown.

However, the present invention relates to the condensation according to synthesis route "A", that is to say of o-phenylenediamines with 1,2-diketones. These condensation reactions are typically carried out in ethanol or acetone as the solvent under reflux in the presence of a catalyst. Numerous catalysts are known for this purpose, including e.g. B. bismuth (III) triflate, gallium (III) triflate, elemental iodine, cerium (IV) ammonium nitrate, manganese (II) chloride, zirconium (IV) chloride, silicate-supported antimony (III) chloride or Heteropoly acids, to name just a few (a summary can be found in Chapter 2.2.2 of "Progress in Quinoxaline Synthesis (Part 1)", VA Mamedov and NA Zhukova, Progress in Heterocyclic Chemistry, Vol. 24,

Elsevier Ltd. (2012), ISSN 0959-6380; http://dx.doi.org/10.1016/B978-0-08-096807- 0.00002-6).

Regarding the ^ -catalyzed condensation of 1,2-diketones with o-phenylenediamines, (Bandyopadhyay et al., "An Effective Microwave-Induced lodine-Catalyst Method for the Synthesis of Quinoxalines via Condensation of 1,2- Diamines with 1, 2-Dicarbonyl Compounds ", Molecules 15, 4207-4212 (2010); doi: 10.3390 / moleculesl 5064207) discloses that it can be accelerated by using microwave radiation. For this purpose, numerous attempts at reaction tem- Temperatures of 50 ° C carried out, the condensation reaction of o-phenylenediamine with phenylglyoxal to 2-phenylquinoxaline was first investigated according to the following scheme 3 in various solvents:

Scheme 3

The solvents tested were methanol, ethanol, THF, dichloromethane, acetonitrile, 1: 1 mixtures of THF or ethanol and water, and water alone, where I2 was added as a catalyst at 5 mol% in each case. The 1: 1 mixture of ethanol and water, in which the reaction after 30 s with a

Conversion of 99% was complete, while in water alone, even after 5 minutes, only a conversion of 36% was observed. As a result, further condensations of o-phenylenediamine with phenylglyoxal, methylphenylglyoxal and benzil in 1: 1 -etha nol / water were carried out, all of which were completed within 2 to 3 minutes with good conversions. For comparison, a reaction between o-phenylenediamine and benzil was carried out without the addition of the iodine catalyst, in which, however, no conversion was observed even after 5 minutes.

Further disclosures of catalyzed syntheses of quinoxalines from o-phenylenediamine in water as a solvent can be found in Hazarika et al. ("Efficient and Green Method for the Synthesis of 1, 5-Benzodiazepine and Quinoxaline Derivatives in Water", in Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry 37 (19), 3447-3454 (2007)) ; More et al. ("Cerium (IV) ammonium nitrate (CAN) as a catalyst in tap water: A simple, proficient and green approach for the synthesis of quinoxalines", Green. Chem. 8, 91-95 (2006)); whereby indium chloride and cerium (IV) ammonium nitrate were used as catalysts. Furthermore, Bachhav et al. the use of glycerine and mixtures of glycerine and water for the catalyst-free synthesis of quinoxalines from various o-phenylenamine derivatives and benzil derivatives, with good conversions being achieved after a reaction time of 4 to 6 hours at a reaction temperature of 90 ° C ("Efficient protocol for the synthesis of quinoxaline, benzoxazole and benzimidazole derivatives using glycerol as green solvent ", Tetrahedron Lett. 52, 5697-5701 (201 1)).

And finally, Delpivo et al., Synthesis 45 (11), 1546-1552 (2013), a process for the production of quinoxalines, among other things, by condensation of optionally substituted o-phenylenediamine with diketones according to the above reaction scheme A under "very gentle reaction conditions "at room temperature in water and various organic solvents. It is disclosed that if aliphatic or mixed aliphatic-aromatic diketones are used, good yields can be achieved within 30 minutes, but not with aromatic diketones such as benzil or dimethoxybenzil, where even after reaction times of 5 h only sales of 10-30% are achieved were. Therefore, these condensations were carried out again using ethanol or methylene chloride as the organic solvent, with conversions of only 40% being achieved in some cases despite three hours of stirring.

The aim of the invention was against this background to develop a rapid, inexpensive and environmentally friendly process for the preparation of quinoxalines, in particular aromatically substituted quinoxalines, from correspondingly substituted o-phenylenediamines.

DISCLOSURE OF THE INVENTION

The present invention achieves this aim by providing a process for the preparation of quinoxalines by condensation of optionally substituted o-phenylenediamine with a diketone according to the following reaction scheme: Scheme 4

wherein:

Ri, R2 and R3 are each independently hydrogen or a monovalent, saturated, unsaturated or aromatic hydrocarbon radical having 1 to 20 carbon atoms, one or more carbon atoms optionally being replaced by heteroatoms, each independently selected from O, N, S, F, CI and Br are selected and n is an integer from 0 to 4;

where optionally two radicals Ri and / or the radicals R2 and R3 are connected to one another and together with the atoms to which they are bonded form a saturated, unsaturated or aromatic ring and / or one Ri of two o-phenylenediamine molecules together for stand a chemical bond and thus form a diaminobenzidine; and

wherein the condensation reaction is carried out in water as a solvent by heating the reactants under pressure to a reaction temperature> 100 ° C.

The process of the present invention is based on the surprising discovery by the inventors that o-phenylenediamines, although they are extremely unstable under the conditions prevailing in the inventive method and react within a few minutes, as will be shown in Comparative Example 1 later, nonetheless in good yields are condensable to the desired quinoxalines - even at temperatures above 200 ° C under high pressures, which is anything but gentle reaction conditions, and without the need for the addition of catalysts. It was also particularly surprising that aromatic diketones, such as. B. benzil and dimethoxybenzil, with which according to the prior art at room temperature only conversions of 10-30% were achieved even after 5 hours, the desired quinoxalines could be obtained within a very short time in yields of over 90%. Furthermore, the inventors surprisingly found that the hydrothermal condensation reaction could be accelerated by adding acetic acid to the aqueous reaction medium, so that roughly the same conversions as in water alone could be achieved within a shorter time. However, since the yields were about the same as when using pure water, the addition of acetic acid apparently had no effect on the stability of the diamine under hydrothermal conditions, but this showed a clear catalytic effect.

Accordingly, in preferred embodiments of the present invention, an aqueous solution of acetic acid, more preferably an approximately 1 to approximately 10%, in particular an approximately 5%, aqueous solution of acetic acid is used as the aqueous solvent.

In a further preferred embodiment of the invention, the reaction mixture is heated to a reaction temperature of at least 200 ° C., in particular to a reaction temperature of about 230 ° C., in order to ensure the fastest possible condensation reactions. Depending on the type of reaction vessel, pressures between 20 and 30 bar were generally established.

In addition, in particularly preferred embodiments, the heating to the hydrothermal conditions is carried out using microwave radiation in the shortest possible time, specifically within just 2 minutes. And moreover, according to the present invention, the high reaction temperature need only be maintained for a period of not more than 10 minutes, preferably not more than 5 minutes.

In preferred embodiments, Ri is hydrogen or n = 0, ie the o-phenylenediamine is unsubstituted. Furthermore, in preferred embodiments of the invention, Ri and R2 are each aromatic radicals, which can sometimes be linked to one another, since the resulting quinoxalines could for the first time be produced in good yields within a short time using water as the sole solvent, and also conjugated aromatic systems which are valuable materials for the manufacture of optoelectronic components. In some preferred embodiments of the invention, the o-phenylenediamine is used in dimeric form, ie one Ri of two o-phenylenediamine molecules together form a chemical bond that connects these molecules to form a dimer, ie a diaminobenzidine, which in particular has 3, Is 3'-diaminobenzidine. Specifically, such dimeric quinoxalines with relatively high molecular weights have not previously been accessible in such a simple manner.

Furthermore, in certain embodiments of the process according to the invention, a further catalyst, in addition to acetic acid, can nonetheless be added in order to further increase the conversion of the condensation reaction in the short reaction times according to the present invention, even if the reaction takes place in a short time even without such an additional catalyst and can be carried out with satisfactory yields.

As mentioned and demonstrated in the following exemplary embodiments, the process according to the invention allows the desired quinoxalines to be synthesized in good yields within a few minutes of reaction time, without the need to add any catalyst.

In a further aspect, the invention also relates to a new substance synthesized for the first time by the inventors, namely the dimeric quinoxaline as a product of the later Example 14, i.e. H. 2,2 ', 3,3'-tetrakis (4-methoxyphenyl) -6,6'-dichinoxaline or 6- (2,3-bis (4-methoxyphenyl) quinoxalin-6-yl) -2,3-bis ( 4-methoxyphenyl) quinoxaline of the following formula (14):

EXAMPLES

The present invention is described in more detail below with reference to non-limiting examples, which are given for the purpose of illustration. example 1

Production of dibenzo [a, c] phenazine (CAS 215-64-5) (1)

o-Phenylenediamine (64.9 mg, 0.6 mmol) was weighed together with 9,10-phenanthrene-quinone (124.9 mg, 0.6 mmol) into a glass microwave insert and mixed with 15 ml of dist. Water layered. A magnetic stir bar was added and the insert sealed and placed in a microwave reactor. The reaction mixture was heated to 230 ° C. over the course of 2 minutes with stirring and held at this temperature for 5 minutes. The reaction mixture was then cooled and the precipitated solid was filtered off. The product was washed with distilled water and dried overnight in a drying cabinet heated to 80 ° C. In this way, 127.9 mg (76.0% of theory) of the title compound were obtained. ¹ H-NMR (250 MHz; CDC) d (ppm): 9.42 (dd, J = 7.3, 2.2 Hz, 2H), 8.55 (dd, J = 7.5, 1.7 Hz, 2H), 8.38 (dd, J = 6.5, 3.5 Hz, 2H), 7, 87 (dd, J = 6.6, 3.5 Hz, 2H), 7.84-7.69 (m, 4H). Example 2

Production of 2,3-diphenylquinoxaline (CAS 1684-14-6) (2)

The synthesis was carried out analogously to Example 1 using o-phenylenediamine (64.9 mg, 0.6 mmol) and benzil (126.2 mg, 0.6 mmol), 107.8 mg (63.6% of theory). Th.) Of the title compound were obtained.

¹ H-NMR (250 MHz; CDC) d (ppm): 8.22 (dd, J = 6.4, 3.4 Hz, 2H), 7.79 (dd, J = 6.4, 3.4 Hz, 2H), 7.53 (dd, J = 7.5, 2.2 Hz, 4H), 7.41 -7.29 (m, 6H).

Example 3

Production of 2,3-bis (4-fluorophenyl) quinoxaline (CAS 148186-43-0) (3)

The synthesis was carried out analogously to Example 1 using o-phenylenediamine (64.9 mg, 0.6 mmol) and 4,4'-difluorobenzil (147.7 mg, 0.6 mmol), 148.9 mg (78 , 0% of theory) of the title compound were obtained. ¹ H-NMR (250 MHz; CDC) d (ppm): 8.22 (dd, J = 6.4, 3.5 Hz, 2H), 7.81 (dd, J = 6.4, 3.4 Hz, 2H), 7.55-7.29 (m, 4H), 7.07 (t, J = 8.6 Hz, 4H). Example 4

Production of 2,3-bis (4-methoxyphenyl) quinoxaline (CAS 7248-16-0) (4)

The synthesis was carried out analogously to Example 1 using o-phenylenediamine (64.9 mg, 0.6 mmol) and 4,4'-dimethoxybenzil (162.2 mg, 0.6 mmol), although the solid formed after the Filter adhered firmly to the filter paper and was therefore dried together with the filter at 80 ° C in a drying cabinet. The solid was then dissolved in a 1: 1 mixture of ethanol and acetone, and the solution was concentrated on a rotary evaporator, 188.3 mg (91% of theory) of the title compound being obtained.

¹ H-NMR (250 MHz; CDC) d (ppm): 8.17 (dd, J = 6.4, 3.4 Hz, 2H), 7.74 (dd, J = 6.4, 3.4 Hz, 2H), 7.50 (d, J = 8.9 Hz, 4H), 6.88 (d, J = 9.0 Hz, 4H), 3.84 (s, 6H).

Example 5

Production of 6-chloro-2,3-di (2-pyridyl) quinoxaline (CAS 17401 -70-6) (5)

Because of the basicity of 2,2'-pyridil, a synthesis in water analogous to Example 1 is not possible. Therefore, 4-chloro-1, 2-phenylenediamine (85.6 mg, 0.6 mmol) and 2,2'-Pyridil (127.3 mg, 0.6 mmol) was weighed into a glass microwave insert with a magnetic stir bar, but the solvent was not covered with water, but with 15 ml of 50% acetic acid (distilled water / glacial acetic acid 1: 1). After heating by means of microwave radiation for 2 minutes and maintaining the reaction temperature for 5 minutes, the reaction mixture was cooled to 55.degree. A few drops of 10% strength aqueous NaOH were added to the black-brown solution obtained, a black-brown precipitate and a yellow-brown suspension forming. The latter was decanted off, and the precipitate was dissolved in acetone and concentrated on a rotary evaporator, 166.4 mg (87% of theory) of the title compound being obtained.

¹ H-NMR (250 MHz; DMSO-de) d (ppm): 8.33-8.22 (m, 4H), 8.04-7.91 (m, 5H), 7.43-7.31 (m, 2H).

Examples 6 to 12

In the following examples, the following general working instruction A, which was only slightly modified compared to Example 1, was used:

o-Phenylenediamine (42.3 mg, 0.4 mmol) was weighed together with the respective diketone (0.4 mmol) in a glass microwave insert and poured into 2 ml of either dist. Suspended water or 5% acetic acid, after which the insert was sealed and placed in a microwave reactor. The reaction mixture was heated to 230 ° C. within 1-2 minutes and held at this temperature for 5, 10 and 30 minutes, respectively. The reaction mixture was then cooled and the precipitated solid was filtered off. The product was washed with distilled water and dried overnight in a drying cabinet heated to 80 ° C. If necessary, a further purification was carried out by means of reprecipitation of the product by dissolving in acetone and precipitation in water or by means of flash column chromatography, eluting with a mixture of petroleum ether and ethyl acetate (6: 4). Examples 6a to 6d

Production of 2,3-Di (2-thienyl) quinoxaline (CAS 81321 -98-4) (6)

The title compound was determined using dist. Water as a solvent in a yield of 64% of theory. Th. After a reaction time of 5 min (Example 6a) and of 87% of theory. Th. After 30 min (Example 6b) and using 5% acetic acid as a solvent in a yield of 76% of theory. Th. After 5 min (Example 6c) and also from 87% of theory. Th. After 10 min (Example 6d) in each case as a yellow solid.

¹ H-NMR (400 MHz, CDC) d (ppm): 8.08 (dd, J = 6.4, 3.4 Hz, 2H), 7.72 (dd, J = 6.4, 3.4 Hz, 2H), 7.50 (dd, J = 5.1, 1.0 Hz, 2H), 7.25 (dd, J = 3.7, 1.0 Hz, 2H), 7.04 (dd , J = 5.0, 3.7 Hz, 2H).

1 ³ C-NMR (100 MHz, CDCla) d (ppm): 146.8, 141, 4, 140.7, 130.4, 129.6, 129.1, 128.9, 127.7.

Examples 7a to 7d

Production of 2,3-di (2-furyl) quinoxaline (CAS 57490-73-0) (7)

The title compound was determined using dist. Water as a solvent in a yield of 63% of theory. Th. After a reaction time of 5 min (Example 7a) and 86% of theory. Th. After 30 min (Example 7b) and using 5% acetic acid as a solvent in a yield of 74% of theory. Th. After 5 min (Example 7c) and from 84% of the theory. Th. Obtained after 10 min (Example 7d) in each case as a gray solid.

¹ H-NMR (400 MHz, CDC) d (ppm): 8.15 (dd, J = 6.4, 3.4 Hz, 1H), 7.76 (dd, J = 6.4, 3, 4 Hz, 1 H), 7.63 (dd, J = 1, 8, 0.7 Hz, 2H), 6.68 (dd, J = 3.4, 0.7 Hz, 1 H), 6, 57 (dd, J = 3.4, 1.8 Hz, 1H).

¹³ C-NMR (100 MHz, CDCls) d (ppm): 151, 0, 144.4, 142.8, 140.8, 130.6, 129.3, 1 13.2,

1 12.1.

Examples 8a and 8b

Production of 2,3-diphenyl-6-methylquinoxaline (CAS 16107-85-0) (8)

The title compound was obtained using 5% acetic acid as a solvent in a yield of 76% of theory. Th. After a reaction time of 5 min (Example 8a) and of 86% of theory. Th. Obtained after 10 min (Example 8b) in each case as a yellow solid.

¹ H-NMR (400 MHz, CDC) d (ppm): 8.07 (d, J = 8.6 Hz, 1 H), 7.96 (s, 1 H), 7.61 (dd, J = 8.6, 1.9 Hz, 1H), 7.54-7.48 (m, 4H), 7.34 (m, 6H), 2.62 (s, 3H).

¹³ C-NMR (100 MHz, CDCls) d (ppm): 153.5, 152.7, 141, 4, 140.6, 139.9, 139.4, 132.4, 130.0, 130.0 , 128.9, 128.8, 128.8, 128.4, 128.2, 22.1. Examples 9a and 9b

Production of 6-benzoyl-2,3-diphenylquinoxaline ((2,3-diphenylquinoxalin-6-yl) -phenylmethanone; CAS 150252-47-4) (9)

The title compound was obtained using 5% acetic acid as a solvent in a yield of 69% of theory. Th. After a reaction time of 5 min (Example 9a) and 80% of theory. Th. After 10 min (Example 9b) in each case as a yellow solid.

¹ H-NMR (400 MHz, CDCls) d (ppm): 8.54 (dd, J = 1, 6, 0.8 Hz, 1 H), 8.36-8.19 (m, 2H), 7 , 91 (dd, J = 8.3, 1.3 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.59-7.50 (m, 6H), 7 , 42-7.30

(m, 6H).

¹³ C-NMR (100 MHz, CDCls) d (ppm): 195.9, 155.3, 154.8, 143.1, 140.3, 138.8, 138.7, 138.4, 137.3 , 133.0, 132.6, 130.3, 130.0, 130.0, 129.91, 129.87, 129.4, 129.3, 128.7,

128.5, 128.5.

Examples 10a and 10b

Production of 2,3-diphenyl-6-nitroquinoxaline (CAS 7466-45-7) (10)

The title compound was obtained using 5% acetic acid as a solvent in a yield of 71% of theory. Th. After a reaction time of 5 min (example 10a) and 80% d. Th. After 10 min (Example 10b) in each case as a yellow solid obtained.

¹ H-NMR (400 MHz, CDCl3) d (ppm): 9.08 (d, J = 2.5 Hz, 1 H), 8.53 (dd, J = 9.2, 2.5 Hz, 1st H), 8.30 (d, J = 9.2 Hz, 1H), 7.62-7.52 (m, 4H), 7.46-7.35 (m, 6H).

¹³ C-NMR (100 MHz, CDCl3) d (ppm): 156.5, 155.8, 148.0, 143.7, 140.1, 138.24, 138.17, 130.9, 130.0 , 129.97, 129.92, 129.8, 128.6, 125.8, 123.5.

Examples 1 1 a and 1 1 b

Production of 6-cyano-2,3-diphenylquinoxaline (2,3-diphenylquinoxaline-6-carbonitrile; CAS 32388-07-1) (11)

The title compound was obtained using 5% acetic acid as the solvent in a yield of 84% of theory. Th. After a reaction time of 5 min (Example 11 a) and 97% of theory. Th. After 10 min (Example 1 1 b) he hold each as a white solid.

¹ H-NMR (400 MHz, CDC) d (ppm): 8.54 (d, J = 1.3 Hz, 1 H), 8.25 (d, J = 8.6 Hz, 1 H), 7 .90 (dd, J = 8.6, 1.8 Hz, 1H), 7.54 (ddq, J = 8.3, 4.4, 1.9 Hz, 4H), 7.45-7, 32 (m, 6H).

¹³ C-NMR (100 MHz, CDCl3) d (ppm): 156.1, 155.5, 142.7, 140.4, 138.3, 138.3, 135.3, 130.9, 130.8 , 130.0, 129.9, 129.8, 129.7, 128.6, 1 18.3, 1 13.4. Examples 12a and 12b

Production of 2,3-diphenyl-6-methoxycarbonylquinoxaline ((2,3-diphenylquinoxaline- 6-carboxylic acid methyl ester; CAS 32387-86-3) (12)

The title compound was obtained using 5% acetic acid as a solvent in a yield of 81% of theory. Th. After a reaction time of 5 min (Example 12a) and 93% of theory. Th. After 10 min (Example 12b) he holds each as a white solid.

¹ H-NMR (400 MHz, CDC) d (ppm): 8.91 (dd, J = 1, 9, 0.6 Hz, 1H), 8.37 (dd, J = 8.7, 1, 9 Hz, 1H), 8.21 (dd, J = 8.7, 0.6 Hz, 1H), 7.54 (m, 4H), 7.33 (m, 6H), 4.02 ( s, 3H). ¹³ C-NMR (100 MHz, CDCls) d (ppm): 166.4, 155.2, 154.5, 143.2, 140.5, 138.6, 132.0, 131, 2, 129.89 , 129.85, 129.5, 129.4, 129.3, 129.2, 128.4, 128.4, 52.6.

Examples 13-15

In the following examples, the above general working method A was modified to the extent that, instead of 0.4 mmol of o-phenylenediamine, its dimer 3,3'-diamino benzidine (42.8 g, 0.2 mmol) was 0.4 mmol of the respective diketone has been implemented.

Examples 13a and 13b

Production of 2,2 ', 3,3'-tetraphenyl-6,6'-dichinoxaline (6- (2,3-diphenylquinoxalin-6- yl) -2,3-diphenylquinoxaline; CAS 161 1 1 -01 -6) (13)

The title compound was obtained using 5% acetic acid as a solvent in a yield of 82% of theory. Th. After a reaction time of 5 min (Example 13a) and 93% of theory. Th. After 10 min (Example 13b) in each case as a yellow solid obtained.

¹ H-NMR (400 MHz, CDC) d (ppm): 8.61 (d, J = 1.9 Hz, 1 H), 8.33 (d, J = 8.7 Hz, 1 H), 8 .24 (dd, J = 8.7, 1.9 Hz, 1H), 7.61-7.53 (m, 4H), 7.42-7.32 (m, 6H).

¹³ C-NMR (100 MHz, CDCls) d (ppm): 154.3, 153.9, 141, 5, 141, 4, 141, 0, 139.03, 139.02, 130.1, 130.0 , 129.7, 129.2, 129.1, 128.5, 127.6.

Examples 14a and 14b

Preparation of 2,2 ', 3,3'-tetrakis (4-methoxyphenyl) -6,6'-dichinoxaline (6- (2,3-bis (4-methoxyphenyl) quinoxalin-6-yl) -2,3- bis (4-methoxyphenyl) quinoxaline) (14)

The title compound was obtained using 5% acetic acid as a solvent in a yield of 82% of theory. Th. After a reaction time of 5 min (example 14a) and 92% d. Th. After 10 min (Example 14b) in each case as a yellow solid obtained.

¹ H-NMR (400 MHz, CDC) d (ppm): 8.56 (s, 1 H), 8.28 (d, J = 8.7 Hz, 1 H), 8.19 (d, J = 8.7 Hz, 1H), 7.55 (d, J = 7.8 Hz, 8H), 6.90 (d, J = 7.8 Hz, 8H), 3.85 (s, 12H) .

¹³ C-NMR (100 MHz, CDCl3) d (ppm): 160.4, 153.6, 153.2, 141, 1, 141, 0, 140.6, 131, 4, 129.6, 129.2 , 127.1, 1 13.9, 55.4.

Examples 15a and 15b

Preparation of 2,2 ', 3,3'-tetra (2-furyl) -6,6'-dichinoxaline (6- (2,3-di (2-furyl) quinoxalin-6-yl) -2,3- di (2-furyl) quinoxaline; CAS 161452-99-9) (15)

The title compound was obtained using 5% acetic acid as a solvent in a yield of 83% of theory. Th. After a reaction time of 5 min (Example 15a) and 94% of theory. Th. After 10 min (Example 15b) in each case as a yellow solid obtained.

¹ H-NMR (400 MHz, CDCls) d (ppm): 8.52 (d, J = 1.8 Hz, 1 H), 8.26 (d, J = 8.78 Hz, 1 H), 8, 18 (dd, J = 8.8, 1.8 Hz, 1H), 7.65 (s, 4H), 6.73 (dd, J = 9.6, 3.4 Hz, 4H), 6, 59 (m, 4H).

¹³ C-NMR (100 MHz, CDCls) d (ppm): 150.9, 144.6, 144.5, 143.4, 142.9, 141, 5, 140.9, 140.5, 129.99 , 129.97, 127.4, 1 13.5, 1 13.5, 1 12.2.

Comparative example 1

In this experiment, o-phenylenediamine was used alone, i.e. without a reaction partner, with 15 ml of distilled water. Water was added and the mixture was heated to 200 ° C. overnight in a steel autoclave. After drying in a high vacuum, an FT-IR-ATR spectrum was recorded. and compared with a spectrum of the starting material before heating, the two curves being superimposed.

Fig. 1 shows this comparison, the curve after exposure to hydrothermal conditions and those of the starting material are shown in bold. It can be seen that practically all of the characteristic bands had disappeared, which means that the o-phenylenediamine had reacted almost completely during the hydrothermal conditions. A rapid NMR analysis showed, however, that not (or not only) the o-quinonediimine or 2,3-diaminophenazine shown in Scheme 2, but a large number of reaction products, had arisen.

For this reason, it was very surprising that it was possible to convert o-phenylenediamine and its likewise oxidation-sensitive dimer 3,3'-diaminobenzidine with various diketones under hydrothermal conditions to give corresponding quinoxalines - and in good yields, provided that Heating to the hydrothermal conditions and the condensation reaction proceed sufficiently quickly.

Claims

PATENT CLAIMS

1. Process for the preparation of quinoxalines by condensation of optionally substituted o-phenylenediamine with a diketone according to the following reaction scheme:

Scheme 4

wherein:

2. The method according to claim 1, characterized in that the solvent is an aqueous solution of acetic acid.

3. The method according to claim 2, characterized in that the solvent is an approximately 1 - to approximately 10% aqueous solution of acetic acid.

4. The method according to claim 3, characterized in that the solvent is an approximately 5% aqueous solution of acetic acid.

5. The method according to any one of claims 1 to 4, characterized in that it is heated to a reaction temperature of at least 200 ° C.

6. The method according to claim 5, characterized in that it is heated to a reaction temperature of about 230 ° C.

7. The method according to any one of claims 1 to 6, characterized in that the heating to the reaction temperature using microwave radiation takes place within 2 minutes.

8. The method according to any one of claims 1 to 7, characterized in that the reaction temperature is maintained for a period of time of not more than 10 minutes.

9. The method according to claim 8, characterized in that the reaction temperature is maintained for a period of not more than 5 minutes.

10. The method according to any one of claims 1 to 9, characterized in that R2 and R3 are each aromatic radicals which are optionally connected to one another.

1 1. The method according to any one of claims 1 to 10, characterized in that one Ri of two o-phenylenediamine molecules together form a chemical bond and thus a diaminobenzidine.

12. The method according to claim 1 1, characterized in that the diamino benzidine is 3,3'-diaminobenzidine.

13. 2,2 ', 3,3'-tetrakis (4-methoxyphenyl) -6,6'-dichinoxaline and 6- (2,3-bis (4-methoxyphenyl) quinoxalin-6-yl) -2, respectively , 3-bis (4-methoxyphenyl) quinoxaline of the following formula

(14)