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CHEMICAL SCIENCES / «ШУШШШМЛУШаИ» #Щ11Ш, 2022
CHEMICAL SCIENCES
УДК 547 (075.8)
Ибраев М.К.
Карагандинский технический университет им. А.С. Сагинова
Нуркенов О.А.
Д.х.н., профессор ТОО «Институт органического синтеза иуглехимии РК»
Такибаева А. Т. Рахимберлинова Ж.Б. Карагандинский технический университет им. А.С. Сагинова
Исабаева М.Б. Карагандинский медицинский университет DOI: 10.24412/2520-6990-2022-15138-62-64 СИНТЕЗ И СТРОЕНИЕ НОВЫХ 4-(4-БРОМ-3,5-ДИМЕТИЛПИРАЗОЛИЛ) БЕНЗАЛЬДЕГИДА В УСЛОВИЯХ КОНВЕКЦИОННОГО НАГРЕВА И МИКРОВОЛНОВОГО ОБЛУЧЕНИЯ
Ibraev M. K.
Karaganda Technical University named after A.S. Saginov
Nurkenov O.A.
LLP "Institute of Organic Synthesis and Carbon Chemistry of the КК"
Takibayeva A. T. Rakhimberlinova Zh.B.
Karaganda Technical University named after A.S. Saginov
Isabayeva M.B.
Karaganda Medical University
SYNTHESIS AND STRUCTURE OF NEW 4-(4-BROMO-3,5-DIMETHYLPYRAZOLYL) BENZALDEHYDE UNDER CONDITIONS OF CONVECTION HEATING AND MICROWAVE
IRRADIATION
Аннотация
В статье представлена методика получения 4-(4-бром-3,5-диметил-1Н-пиразол-1-ил)бензальдегида в классических и условиях микроволнового облучения. Состав и строение синтезированных соединений подтверждены данными элементного анализа, ИК и ЯМР1Н спектроскопии. Abstract
The article presents methods for obtaining 4-(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)benzaldehyde in classical and microwave irradiation conditions. The composition and structure of the synthesized compounds are confirmed by the data of elemental analysis, IR and NM1H spectroscopy.
Ключевые слова: конвекция, микроволновое облучение, бензальдегид, пиразол, ароматический альдегид Key words: convection, microwave irradiation, benzaldehyde, pyrazole, aromatic aldehyde.
The chemistry of heterocyclic compounds is currently developing at a very intensive pace. This is primarily due to the significant theoretical and, especially, practical significance that organic compounds of nitrogen and sulfur have acquired due to their useful properties.
The use of nitrogen- and sulfur-containing organic compounds as insecticides in agriculture, medicines for the treatment of eye diseases, malignant neoplasms, viral infections, flotation reagents in the mining industry, polymer stabilizers, antioxidants for industry, polymer stabilizers, antioxidants for lubricating oils, for the manufacture of non-combustible materials and fabrics is widely known.
Among them, due to greater preparative availability, pyrazole derivatives occupy a special place [1-3].
In medicine, pyrazole-containing compounds, as well as their derivatives, belong to the oldest anti-inflammatory and analgesic medicinal substances [4, 5]. Therefore, the synthesis of new pyrazole-containing synthons is one of the promising directions in the search for new biologically active substances.
Since aldehydes are important synthons in the organic synthesis of various classes of compounds, including heterocyclic ones, we tried to obtain an aromatic aldehyde based on 4-bromo-3,5-dimethylpyrazole and 4-fuorobenzaldehyde. The paper [6] describes methods for obtaining monosubstituted aromatic aldehydes from the corresponding amines (morpholine, piperidine) and o-fuorobenzaldehydes when they are boiled in a DMFA solution in the presence of potash.
The synthesized amino-substituted aromatic aldehydes are further used for the synthesis of important heterocyclic spiro derivatives of quinolines. These reactions with halogenated aldehydes are interesting because the undivided pair of the fluorine atom is in a p, n -conjugation with a double bond or a n -electron ring system.
It should also be noted that in the reaction of nucleophilic substitution of alkyl halides, the best nucleophiles were iodide and bromide ions, and the fluoride ion was the most difficult to escape group. The
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reverse sequence is more often observed in the SnAt mechanism - fluorinated substrates react at a higher rate in the presence of electron acceptor substituents in the ortho- and para-positions of the ring. These features of the electronic structure of fluorobenzaldehydes are of particular scientific interest.
In this regard, it seemed interesting for us to obtain an aromatic aldehyde containing a biologically active pyrazole-containing fragment in the para-position of the aromatic core. By analogy with the described technique [7-10], we performed the substitution of a
fluorine atom in 4 fluorobenzaldehyde for a pyrazole fragment.
As a result of the conducted studies, it was found that the interaction of 4-bromo-3,5-dimethylpyrazole with 4-fluorobenzaldehyde during their boiling in a DMFA medium in the presence of potash for 20 hours leads to the formation of 4-(4-bromo-3,5-dimethyl-1H-pyrazole-1-yl)benzaldehyde (1). The reaction, most likely, follows the mechanism of «attachment-cleavage».
Usually, nucleophilic substitution reactions with fluorobenzaldehyde are characterized by the duration of the process and are carried out at high temperatures and is associated with the nature of the C-F bond. As a result of studying this reaction, it was found that the reaction of obtaining 4-(4-bromo-3,5-dimethyl-1H-pyrazole-1-yl)benzaldehyde (1) can be successfully carried out in a DMFA environment under microwave activation conditions.
To carry out the reaction, we used a specially prepared catalyst on a «Silpearl» silica gel substrate activated with twice the amount of potash [11-15].
The reaction of nucleophilic substitution of a fluorine atom in 4-fluorobenzaldehyde for a pyrazole residue was carried out in the presence of a catalyst of the above catalyst at a temperature of 1400C for 5 hours in a DMFA medium, increasing the reaction time by 4 times. The yield of product 1 was 66%.
The composition and structure of the synthesized compound 1 are confirmed by the data of elemental analysis, IR and NMR 1H spectroscopy.
In the IR spectrum of compound 4, there is an intense absorption band in the region of 1697 cm-1, characteristic of the carbonyl (C =O) of the aldehyde group. In the NMR spectrum (DMSO-d6, 500 MHz) of compound 1, the signals of two methyl protons of the pyrazole fragment are registered as two singlets in the
region of 1.22 and 1.40 m.d. Two doublets in the region of 7.79 and 8.05 m.d. correspond to ortho and metaprotons of the pyrazole substituted phenyl fragment. The aldehyde proton manifests as a narrow singlet at 10.06 m.d. (Figure 1).
Method of synthesis of 4-(4-bromo-3,5-dimethyl-1H-pyrazole-1 -yl)benzaldehyde (1):
a) in classical conditions. To a solution of 1.24 g (0.01 mol) of 4-fluorobenzaldehyde in 20 ml of DMFA, 2 g (0.0113 mol) of 4-bromo-3,5-dimethylpyrazole and 2.07 g (0.015 mol) of potash were added. The reaction mixture was boiled in a glycerin bath with a reverse refrigerator at a temperature of 140-150° C for 20 hours . The completion of the reaction was controlled by thin-layer chromatography. The solution was cooled, the potash was filtered and the solvent was evaporated. The remaining precipitate was recrystallized from 2-propanol, 1.68 g (60%) of compound 1 with a melting point of 109-110°C was obtained. IR spectrum, v, cm-1685 (C=O). NMR spectrum 1H, 5, m.d.: 2.12 s (3H, CH3), 2.39 s (3H, CH3), 7.79 d (1H, SNrom, JHH 7.8 Hz), 8.05 d (1H, CHarom, JHH 7.9 Hz), 10.07 s [1H, S(O)H]. Found (%): C, 52.83; H, 4.17; N, 10.19.C12H11N20Br. Calculated (%): C, 51.63; H, 3.97; N, 10.04.
64 CHEMICAL SCIENCES / «ШУУШШУМЛУШаИ» #Щ1ШШ, 2022
Figure 1 - NMR 1Hspectrum 4-(4-bromo-3,5-dimethyl-1H-pyrazole-1-yl)benzaldehyde (1)
b) under conditions of microwave irradiation. To a solution of 0.62 g (0.005 mol) of 4-fluorobenzaldehyde in 10 ml of DMFA, 1 g (0.0056 mol) of 4-bromo-3,5-dimethylpyrazole and 1.54 g of catalyst were added. The reaction mixture was subjected to microwave irradiation in the Monowave 300 Anton Paar microwave unit (Austria) at a temperature of 140 ° C for 5 hours
After the end of the reaction, the reaction mixture was filtered from the catalyst and the solvent was evaporated. The resulting precipitate was recrystallized from 2-propanol, 0.92 g (66%) of compound 1 was obtained with a melting point of 109-110°C Thus, synthesized 4-(4-bromo -3,5 -dimethyl-1H-pyrazo le-1-yl)benzaldehyde is an interesting reactive synthon for a variety of chemical transformations.
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