REACTION OF 6-AMINOQUINAZOLIN-4-ONE WITH AROMATIC ALDEHYDES

ABSTRACT

In this research work, the reactions of the bicyclic compound 6-aminoquinazolin-4-one with aromatic aldehydes containing the functional groups –NO₂, –OH, –N(CH₃)₂, –OCH₃ were studied. Factors influencing the reaction process and product yield are identified, and optimal conditions are presented. The structure of the synthesized compounds was proven using modern physical research methods.

АННОТАЦИЯ

В данной исследователской работе изучены реакции бициклического соединения 6-аминохиназолин-4-она с ароматическими альдегидами, содержащими функциональные группы –NO₂, –OH, –N(CH₃)₂, –OCH₃. Выявлены факторы, влияющие на процесс реакции и выход продукта, и представлены оптимальные условия. Структура синтезированных соединений доказана с использованием современных физических методов исследования.

Keywords: quinazolin-4-one, heterocyclic compound, aromatic aldehydes, electrondonor, electronacseptor, recrystallization, activated carbon, chromatography, IR-spectroscopy, NMR-spectroscopy.

Ключевые слова: хиназолин-4-он, гетероциклическое соединение, ароматические альдегиды, электронодонор, электроноакцептор, перекристаллизация, активированный уголь, хроматография, ИК-спектроскопия, ЯМР-спектроскопия.

Introduction. Natural and synthetic heterocyclic compounds containing the benzopyrimidine family are widespread in the world and are part of many drugs used in agriculture, animal husbandry and medicine [1; 29-38 pp., 2; 64-67 pp., 3; 380-384., 4; 989-994 pp., 5; 2440-2445 pp., 6; 51-55 pp.]. These compounds include synthetic quinazolin-4-ones, their analogs and derivatives. For example, one can see that synthetic quinazoline derivatives used in medicine have high psychotropic (methaqualone), diuretic (kinetasone), cardiovascular (prazosin) and antiviral (quinazoline analogues of efavirenz) activity [7; 18-27 pp., 8; 1-15 pp., 9; 6042-6054 pp., 10; 411-422 pp.]. In addition, the authors note that the compound 2-methoxycarbonylaminoquinazolin-4-one, synthesized on the basis of quinazolin-4-one, is a highly effective agent in the complex fight against cotton gommosis and root rot diseases in agriculture [11; 56-71 pp.]. Therefore, as a result of scientific research carried out in the field of organic chemistry, among heterocyclic compounds containing nitrogenous and benzene groups in their molecules, the number of various biologically active drugs is increasing.

In this article, the quinazolin-4-one compound selected as the starting material was synthesized using the Nimentovsky method, then the quinazolin-4-one compound was treated with a nitration mixture (concentrated H₂SO₄ acid (ρ=1.835 g/cm³), HNO3 (ρ =1.65 g/cm³ )) was nitrated and the 6-nitroquinazolin-4-one compound synthesized accordingly was returned in the presence of SnCl₂•2H₂O, and the synthesis of 6-aminoquinazolin-4-one is detailed in the literature sources [2; 64-67 pp., 3;  380-384 pp.]. In this research, the reactions of the bicyclic 6-aminoquinazolin-4-one compound with aromatic aldehydes were studied.

Methods and materials

IR-spectra of the synthesized compounds were recorded on Perkin-Elmer IQ-Fure Cistema 2000 spectrometer on KBr tablets, NMR ¹H, ¹³C spectra on Unity-400+ with an operating frequency of 400 MHz and Jeol-600 with an operating frequency of 600 MHz (internal standard GMDS, δ-scale) were obtained in deuterylated DMSO-d6 + CCl₄, CD₃COOD solns. The purity of the product was determined by the method of thin-layer chromatography ‘Sorbfil’ (Russia), the melting point of the synthesized compounds was determined by the equipment ‘BOETIUS’ (Germany) and ‘MEL-TEMP’ (USA).

Experimental part

Synthesis of 6-[(4-Nitrobenzylidene)amino]N-3(H)-quinazolin-4-one.

The reaction was carried out in a single-mouth, round-bottomed, temperature-resistant flask equipped with a reflux condenser. First, 0.161 g (1 mmol) of 6-aminoquinazolin-4-one and 0.151 g (1 mmol) of p-nitrobenzaldehyde were dissolved in 5 ml of ethyl alcohol (ρ=0.7893 g/cm3), and both solutions were was placed in a pre-prepared one-necked flask and heated at 40-45 ^oC for 2 hours. The reaction mixture was left at a temperature of 25-27 ^oC for 10 hours. The precipitate was filtered and washed with water, dried in a drying oven. The obtained technical product was recrystallized in dimethylformamide. Product formation during the reaction was monitored by thin-layer chromatography. System – chloroform:methanol:benzene 5:3:1.

Synthesis of  6-((4-hydroxybenzylidene)amino)quinazolin-4(3H)-one, 6-((4-(dimethyl amino)-benzylidene)amino)quinazolin-4(3H)-one, 6-((4-(methoxy benzylidene)amino)-quinazolin-4-(3H)-ones.

The reaction was carried out in the above-mentioned analogous method in the presence of ethanol for 2 hours in the ratio of substances 1:1, the synthesized compounds were synthesized in yields of 37-42-46%, respectively, and the reaction mixture was processed in the laboratory. The system is acetone: benzene 3:2.

Results and discussion

The reaction of 6-aminoquinazolin-4-one with p-nitrobenzaldehyde is due to the breaking of the carbon-oxygen bond in p-nitrobenzaldehyde. In this case, the electron cloud (density) in the carbonyl group of p-nitrobenzaldehyde is shifted towards the oxygen atom, that is, the density of positive charges on the carbon atom increases, and the density of negative charges on oxygen increases, and it remains electronegatively charged with respect to carbon, and the carbonyl group is polarized. As a result, the carbon atom of the carbonyl group has an electrophilic property and combines with nucleophilic reagents. Therefore, during p-nitrobenzaldehyde joining reaction, nucleophilic addition of positively charged carbon atom to negatively charged nitrogen atom of 6-aminoquinazolin-4-one occurs. The proposed reaction equation mechanism is as follows:

Figure 1. Synthesis reaction of 6-[(4-nitrobenzylidene)amino]N-3(H)-quinazolin-4-one

When the structure of the synthesized 6-[(4-nitrobenzylidene)amino]N-3(H)-quinazolin-4-one was analyzed by the IR spectrum, the C=O group in the fourth position has a valence vibration of 1697 cm^-1, the third it was observed that valence vibrations of the NH group in the 3438 cm^-1 region, the C=N group in the 1618 cm^-1 region, the C-C group in the 1519 cm^-1 region, the C-N group in the 1279 cm^-1 region, and the C–H group in the 2918 cm^-1 region. During the research, ¹H, ¹³C NMR spectra of 6-[(4-nitrobenzylidene)-amino] N-3(H)-quinazolin-4-one were obtained.

Figure 2. 6-[(4-Nitrobenzylidene)amino]N-3(H)-quinazolin-4-one ¹H NMR spectrum

In the weak field of the ¹H NMR spectrum, the value of the H-2 proton of aromatic protons is 7.96 ppm in the field, chemical shift appears in the form of a one-proton doublet (J=2.42 Hz), the value of the H-5 proton is 8.92 ppm is observed in the field as a one-proton singlet, and the value of the H-7 proton is 7.75 ppm in the field in the form of one-proton doublet-doublet (J^M=2.45, J^o=8.6 Hz), and H-8 is 7.69 ppm in the form of a one-proton doublet (J=8.55 Hz), the H-10 proton value is 7.96 ppm appears in the form of a singlet, according to which the proton of the olefin (CH=N) of the azomethine bond is shifted to a weaker area at 12.18 ppm was observed in the form of a one-proton singlet, aromatic protons belonging to p-NO₂-benzylidene due to spin-spin interaction, H-2',6' protons in the form of a two-proton triplet-triplet (J=8.86 Hz) at 8.25 ppm., H-3' and the fact that, 5' protons appeared as a two-proton triplet-triplet (J=8.79 Hz) at 8.35 ppm under the influence of the NO₂-group is 6-[(4-nitrobenzylidene)amino]N-3(H)-quinazolin-4-one fully confirms that. The signals belonging to the ¹³C NMR spectrum of this substance are the following ppm appeared in the fields.

¹³С NMR: (DMSO-d₆ + ССl₄): δ, ppm J/Hz) 600. In this case, C-1' in the composition is 128.1 ppm in the field, 116.6 ppm in area C-2, 144.3 ppm in area C-3', 5', 141.2 ppm in the field C-2', 6', 148.3 ppm in area C-4a, 158.9 ppm in area C-4, 160.4 ppm in the area C-4', 128.2 ppm in area C-5, 129.5 ppm in the field C-6, 123.4 ppm in the field C-7, 123.3 ppm C-8 in the field, and C-8a 147.6 ppm it was determined to be manifested in the fields.

During the research, the synthesis of 6-((4-hydroxybenzylidene) amino) quinazolin-4(3H)-one, 6-((4-(dimethyl amino) benzylidene) amino) quinazolin-4(3H)-one, 6-((4-(methoxy benzylidene) amino) quinazolin-4-(3H)-ones was carried out similarly to the synthesis of 6-[(4-nitrobenzylidene) amino] N-3(H)-quinazolin-4-one. In this case, 6-aminoquinazolin-4-one reacts with aromatic aldehydes containing an electron-donating group (–OH, –N(CH₃)₂, –OCH₃) in two different solvents, ethyl alcohol and pyridine, which have different polarities, the amount of substances is also in different proportions, and the temperature was in the range from 40°С to 110°С. The result is 6-((4-hydroxybenzylidene) amino) quinazolin-4(3H)-one, 6-((4-(dimethyl amino)-benzylidene) amino) quinazolin-4(3H)-one, similar to 6-((4-(methoxy benzylidene) amino)-quinazolin-4-(3H)-one compounds were synthesized in yields of 37-42-46 %, respectively. The reaction equation was proposed as follows:

Figure 3. Reaction of 6-aminoquinazolin-4-one with aromatic aldehydes

It can be seen from the given reaction that aromatic, heterocyclic compounds containing an amino group react with various aldehydes to form the corresponding benzylidene compounds. Some physicochemical properties of the synthesized compounds are listed in table 1.

Table 1.

Physicochemical quantities of synthesized compounds

Conclusion. In conclusion, it can be said that when the reaction of 6-aminoquinazolin-4-one with aromatic aldehydes was carried out in ethanol and pyridine solvents of different polarity at a temperature of 40-45 ^oC, it was found that the product yield was higher in ethanol than in pyridine. The physicochemical constants of these newly synthesized compounds and their structure have been proven using modern physicochemical research methods.

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