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REACTIONS OF 4,6-DIAMINO-2-MERCAPTOPYRIMIDINE WITH MONOCHLOROACETIC ACID ETHERS
Gulrukh Salieva
Doctoral student of the National University of Uzbekistan, Uzbekistan, Tashkent E-mail: [email protected]
Mukhanbek Turlibekov
Master student of the National University of Uzbekistan, Uzbekistan, Tashkent E-mail: [email protected]
Tursunali Kholikov
Head of the Department of Organic Chemistry of the National University of Uzbekistan, Uzbekistan, Tashkent E-mail: [email protected]
Alimjon Matchanov
Professor
of Academy of Sciences of the Republic of Uzbekistan, Institute of Bioorganic Chemistry, Uzbekistan, Tashkent E-mail: [email protected]
РЕАКЦИИ 4,6-ДИАМИНО-2-МЕРКАПТОПИРИМИДИНА С ЭФИРАМИ МОНОХЛОРУКСУСНОЙ КИСЛОТЫ
Салиева Гулрух Баходировна
докторант
Национального университета Узбекистана, Узбекистан, г. Ташкент
Турлибеков Муханбек Мейрбекович
магистр
Национального университета Узбекистана, Узбекистан, г. Ташкент
Холиков Турсунали Суюнович
заведующий кафедрой органической химии Национального университета, Узбекистана, Узбекистан, г. Ташкент
Матчанов Алимжон Давлатбоевич
проф.
Академии наук Республики Узбекистан, Институт биоорганической химии, Узбекистан, г. Ташкент
ABSTRACT
Derivatives based on 2-mercaptopyrimidine have high biological activity, so the development of new methods of synthesis of these compounds is of great importance. This work presents the synthesis method of S-alkyl derivatives of py-rimidine based on 4,6-diamino-2-mercaptopyrimidine. The structure of compounds were elucidated by IR, HRMS. Cleanness of compounds was examined at TLC.
Библиографическое описание: REACTIONS OF 4,6-DIAMINO-2-MERCAPTOPYRIMIDINE WITH MONOCHLOROACETIC ACID ETHERS // Universum: химия и биология : электрон. научн. журн. Salieva G. [и др.]. 2025. 2(128). URL: https://7universum. com/ru/nature/archive/item/19187
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АННОТАЦИЯ
Производные на основе 2-меркаптопиримидина обладают высокой биологической активностью, поэтому разработка новых методов синтеза этих соединений имеет большое значение. В данной работе представлен метод синтеза S-алкилпроизводных пиримидина на основе 4,6-диамино-2-меркаптопиримидина. Структура соединений установлена методами ИК, HRMS. Чистота соединений проверена методом ТСХ.
Keywords: 4,6-diamim-2-mercaptopyrimidine, methyl (ethyl) ester of monochloroacetic acid, alkylation.
Ключевые слова: 4,6-диамино-2-меркаптопиримидин, метиловый (этиловый) эфир монохлоруксусной кислоты, алкилирование.
Introduction
Many biologically active substances have been synthesized on the basis of substituted pyrimidine and are widely used in medicine today. These compounds are anticancer [13, p. 738-742], in the treatment of increased immunodeficiency syndrome (AIDS) [11, p. 60-66], antidiabetes [7, p. 3445-3448], antibacterial [10, p. 4424-4426], including anti-inflammatory drugs. Also, their derivatives are used in agro-industry [9, p. 946-952] and is also used as a fungicide [15, p. 887896].
Pyrimidine derivatives have been identified as effective platelet aggregation inhibitors. In particular, alkylthio-substituted pyrimidines have attracted the attention of scientists with their activity against platelet aggregation [2, p. 4612-4621. 8, p. 5919-5923. 6, p. 213220. 3, p. 6103-6104]. Some of these have been extensively tested in the development of adenosine diphosphate (ADP) receptor antagonists.
Breault et al presented an efficient synthetic method for the synthesis of pteridinedione derivatives based on 2-thio-4,6-diamino pyrimidine. These reactions provided a simple and efficient way to produce pteridinedione derivatives for biological evaluation as inhibitors of glutamate racemase (MurI) in Grampositive bacteria [1, p. 6100-6103].
Fischer Gillerman and others carried out the benzylation, alkylation, nitrosation and reduction reaction of 4,6-diamino-2-mercaptopyrimidine [4, p. 245-256. 14, p. 49-53. 5, p. 430-433]. Podzigun et al. They extensively studied the chemical properties of acyl derivatives of 4,6-diamino-2-mercaptopyrimidine and showed that three main products are formed as a result of acylation with carbocyclic acid chlorides: 2-acylthio-4,6 -diaminopyrimidines, 1 -acyl-4,6-diamino -1,2-dihydro-2-pyrimidinethiones, and 6-amino-4-acylamido-1H(3H)-dihydro-2-pyrimidinethiones. 2-acylthio-4,6-diaminopyrimidines and 1-acyl-4,6-diamino-1,2-dihydro-2-pyrimidinthiones react with water, alcohols and amines under mild conditions
to give 4,6-diamino-2- mercaptopyrimidine and corresponding carboxylic acid derivatives. The authors also noted that 2-acylthio-4,6-dimethylpyrimidines react similarly with nucleophiles, while 6-amino-4-acylamido-1H(3H)-dihydro-2-pyrimidinethione remains stable in alcohols under boiling conditions. Treatment of this compound with sodium hydroxide and alcohol solution led to the formation of sodium salts, which were alkylated with alkyl halides in DMF at 50-60°C to give 2-alkylthio derivatives. Significantly, 6-amino-4-acylamido-1H(3H)-dihydro-2-pyrimidinthione underwent S-acylation when reacted in the presence of benzoyl chloride and triethylamine at 20-80°C. The results of this study highlight the utility of acylated derivatives of 4,6-diamino-2-mercaptopyrimidine in synthetic applications, particularly as nucleophilic reagents and acylating agents [12, p. 1820-1823]. The purpose of this article is to conduct alkylation reactions based on 4,6-diamino-2-mercaptopyrimidine with monochloroacetic acid methyl (ethyl) ether and study their structure.
Results and discussion
The high reactivity of amino and mercapto groups was taken into account in the synthesis of S-alkyl derivatives using the literature information given above, and the reaction was carried out with methyl and ethyl esters of chloroacetic acid in DMF solvent at 50 °C for two hours, as a result of which S-acetyl compounds were formed. The duration of the reaction was determined by TLC (scheme 1). After the reaction was completed, the mixture was cooled to room temperature. During the reaction, S-C bond formation was observed, which confirms the formation of thioethers. Synthesis methods were carried out with high yield and selectivity, which indicates that optimal conditions were chosen. IR and HRMS spectra of the obtained compounds were obtained.
rN CICH?COOR ^
, - Дч. DMF, 50 °C, 2 h. H2N N SNa H2N N SR
R = Me, Et.
Scheme 1. Synthesis S-asetate derivatives of 4,6-diamini-2-mercaptopyrimidine
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IR spectrum of methyl 2-((4,6-diamino)pyrimidin-2-yl)thio)acetate. Broad absorption lines at 3458 cm-1, 3359 cm- and 3199 cm- corresponded to N-H valence vibrations of amine groups in the pyrimidine ring, absorption lines at 2979 cm- was consistent with C-H valence vibrations of aliphatic methylene and methyl groups, which showed the presence of alkyl groups. The clear absorption line at 1724 cm- corresponded to the C=O valence vibration of the ether group in the acetate and confirmed the formation of the ether functional group. Absorption lines at 1614 cm- and 1576 cm-were identified as aromatic pyrimidine and valence vibrations of C=N and C=C bonds, which indicated the
preservation of aromatic properties. The absorption lines at 1545 cm- and 1464 cm- corresponded to the valence vibrations of the aromatic C=C and C=N bonds, indicating the presence of a bonded aromatic system in the compound. at 1298 cm- correlated to the valence vibrations of the C-S-C bond. This proves that a bond is formed between the pyrimidine ring of the thioether group and the ether functional group. These IR data confirm the successful synthesis and proposed chemical structure of Methyl (ethyl) 2-{(4,6-diamino)pyrimidin-2-yl)thio}acetate (Figure 1).
Figure 1. a) IR spectra of methyl 2-((4,6-diamino)pyrimidin-2-yl)thio)acetate. b) IR spectra of ethyl 2-((4,6-diamino)pyrimidin-2-yl)thio)acetate
HRMS analysis of methyl 2-{(4,6-diamino)pyrimidin-2-yl)thio}acetate revealed a protonated molecular ion [M+H+] at m/z 215.0602. The theoretically calculated value for molecular formula C7H11N4O2S is m/z 215.2505. These results provide additional evidence for the molecular structure of methyl 2-{(4,6-diamino)pyrimidin-2-yl)thio}acetate.
HRMS analysis of ethyl 2-{(4,6-diamino)pyrimidin-2-yl)thio}acetate showed protonated molecular ion [M+H+] at m/z 229.0764. The theoretically calculated value for the molecular formula C7H11N4O2S is m/z 229.0754. These results provide additional evidence for the molecular structure of ethyl 2-{(4,6-diamino)pyrimidin-2-yl)thio}acetate.
Experimental part
IR spectrum was recorded on a SHIMADZU IR-4000. High-resolution mass spectrum (HRMS) was recorded under Bruker micro TOF focus conditions. All used reagents are commercially available. They were purchased from Sigma-Aldirich.
50 mg in a double-necked round-bottom flask equipped with a reflux condenser. (0.351 mmol) Na salt of DAMP was added and dissolved in 5.0 mL DMF, then monochloroacetic acid methyl (ethyl) ether (0.351 mmol) was added to the mixture, and the reaction mixture was stirred at 50-60 oC for 2 hours. The duration
of the reaction was determined by TLC. After the reaction was completed, the mixture was cooled to room temperature, and the solvent was removed from the reaction mixture using a rotary evaporator. The reaction product was purified by column chromatography.
Synthesis of methyl 2-((4,6-diamino)pyrimidin-2-yl)thio)acetate
The yield is 113.1 mg. (75%). Methyl 2-{(4,6-diamino)pyrimidin-2-yl)thio}acetate - brown liquid substance Rf = 0.62 (system: ethyl acetate: hexane 1:2). IR spectrum are 3458, 3357, 3199, 2929, 2359, 2204, 1724, 1614, 1545, 1464, 1370, 1298, 1150, 800 cm-1. 1H- NMR (600 MHz, CD3OD) 5: 3.69 (s, 3H, CH3), 3.87 (s, 2H, CH2), 5.26 (s, 1H, 2CH-pyrimidine). HRMS (ESI-TOF) m/z; [M+H+] calculated C7H11N4O2S = 215.2505, found 215.0602.
Synthesis of ethyl 2-((4,6-diamino)pyrimidin-2-yl)thio)acetate
The yield is 54.38 mg. (67%). Ethyl 2-{(4,6-diamino)pyrimidin-2-yl)thio}acetate - brown liquid substance Rf = 0.62 (system: ethylacetate: hexane 1:2). IR spectrum are 3458, 3357, 3199, 2929, 2359, 2204, 1724, 1614, 1545, 1464, 1370, 1298, 1150, 800 cm-1. HRMS (ESI-TOF) m/z; [M+H+] calculated C7H11N4O2S = 229.0754, found 229.0764.
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Conclusion were determined by IR spectroscopy and HRMS proved
A»., n • ^ on the basis of mass spectrometry methods.
Methyl 2-{(4,6-diamino)pyrimidin-2-yl)thio}ace-
tate and ethyl 2-{(4,6-diamino)pyrimidin-2-yl)thio}ace-
tates were synthesized and their chemical structures
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