Metal-free, acid-base, and organocatalyst-promoted semi-green protocols for the efficient construction of structurally diverse & highly functionalized pyrimidine derivatives: A long-term review (1876–2026)

Authors

DOI:

https://doi.org/10.14295/bjs.v5i8.898

Keywords:

pyrimidine synthesis, metal-free, organocatalysis, semi-green protocols, acid-base promotion

Abstract

This review summarizes the 150-year development of pyrimidine synthesis from 1876 to 2026, highlighting progress in metal-free, acid–base-mediated, and organocatalytic methodologies for the construction of structurally diverse, highly functionalized pyrimidine derivatives. Emphasis is placed on the synthetic efficiency, practical applicability, and sustainability of these approaches, including classical condensation reactions and modern semi-green methodologies. This review aims to serve as a comprehensive reference for the development of efficient, sustainable, and metal-free strategies for the synthesis of complex pyrimidine scaffolds.

References

Abdelrehim, E. S. M., & El-Sayed, D. S. (2022). Synthesis, screening as potential antitumor of new poly heterocyclic compounds based on pyrimidine-2-thiones. BMC Chemistry, 16. https://doi.org/10.1186/s13065-022-00810-4 DOI: https://doi.org/10.1186/s13065-022-00810-4

Adly, M. E., Edris, N. A., Kadry, H. H., & Shalaby, A. T. (2024). Pyrimidine-5-carbonitriles: A review of available synthetic approaches and biological evaluation. Egyptian Journal of Chemistry. DOI: https://doi.org/10.21608/ejchem.2024.264757.9231

Agbaje, O. C., Fadeyi, O. O., Fadeyi, S. A., Myles, L. E., & Okoro, C.O. (2011). Synthesis and in vitro cytotoxicity evaluation of some fluorinated hexahydropyrimidine derivatives. Bioorganic & Medicinal Chemistry Letters, 21(3), 989-992. https://doi.org/10.1016/j.bmcl.2010.12.022 DOI: https://doi.org/10.1016/j.bmcl.2010.12.022

Ahmad, O. K., Hill, M. D., & Movassaghi, M. (2009). Synthesis of densely substituted pyrimidine derivatives. The Journal of Organic Chemistry, 74(21), 8460-8463. https://doi.org/10.1021/jo9017149 DOI: https://doi.org/10.1021/jo9017149

Akhaja, T. N., & Raval, J. P. (2011). 1,3-dihydro-2H-indol-2-ones derivatives: Design, Synthesis, in vitro antibacterial, antifungal and antitubercular study. European Journal of Medicinal Chemistry, 46(11), 5573-5579. https://doi.org/10.1016/j.ejmech.2011.09.023 DOI: https://doi.org/10.1016/j.ejmech.2011.09.023

Al-Hussein, I. R. A., & Al-Shuhaib, Z. A. M. (2023). Synthesis and characterization of some new pyridine and pyrimidine derivatives. Baghdad Science Journal, 20(3). https://doi.org/10.21123/bsj.2022.7012 DOI: https://doi.org/10.21123/bsj.2022.7012

Albratty, M., & Alhazmi, H. A. (2022). Novel pyridine and pyrimidine derivatives as promising anticancer agents: A review. Arabian Journal of Chemistry, 15, 103846. DOI: https://doi.org/10.1016/j.arabjc.2022.103846

Alamshany, Z. M., & Nossier, E. S. (2024). New thiazole derivatives linked to pyridine, fused pyridine, pyrimidine and thiazolopyrimidine scaffolds. Journal of Molecular Structure, 1316, 138973. https://doi.org/10.1016/j.molstruc.2024.138973 DOI: https://doi.org/10.1016/j.molstruc.2024.138973

Atwal, K. S., O’Reilly, B. C., Gougoutas, J. Z., & Malley, M. F. (1987). Synthesis of substituted 1,2,3,4-tetrahydro-6-methyl thioxo-5-pyrimidinecarboxylic acid esters. Heterocycles, 26, 1189-1192. https://doi.org/10.3987/R-1987-05-1189 DOI: https://doi.org/10.3987/R-1987-05-1189

Elderfield, R. C. (1957). Heterocyclic Compounds. New York, NY, USA: John Wiley & Sons, 6th edition.

Bhat, M. A., Al-Dhfyan, A., & Al-Omar, M. A. (2016). Targeting cancer stem cells with novel 3,4-dihydropyrimidine-2(1H)-one/thiones. Molecules, 21, 1746. https://doi.org/10.3390/molecules21121746 DOI: https://doi.org/10.3390/molecules21121746

Bhargav, A, Narendra, B., Gowda, & Pavan Kumar, C, (2021). Synthesis, characterization and biological evaluation of substituted pyrimidines. International Journal of Pharmaceutical Research and Applications, 954-962. https://doi.org/10.35629/7781-0605954962

Balaji, P. N., Sreevani, M. S., Harini, P., Rani, J., P., Prathusha, K., & Chandu, T. J. J. (2010). Chemical & Pharmaceutical Research, 2, 754-758.

Biginelli, P. (1983). Synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Gazz Chim Ital, 23, 360-416.

Brown, D. J. (1986). Comprehensive heterocyclic chemistry. Oxford, UK: Pergamon Press, 14, edited by A. R. Katritzky, A. R., & Rees, C. W.

Bruice, P. Y. (2007). Organic Chemistry. 3rd edition, Singapore: Pearson Education.

Chaudhary, A., Sharma, P. K., Verma, P., & Dudhe, R. (2011). Synthesis of novel pyrimidine derivative and its biological evaluation. Analele UniversităŃii din Bucureşti – Chimie, 20(02).

Chikhale, R. V., Bhole, R. P., Khedekar, P. B., & Bhusari, K. P. (2009). Synthesis and pharmacological investigation of 3-(substituted-1-phenylethanone)-4-(substituted phenyl)-1, 2, 3,4-tetrahydropyrimidine-5-carboxylates. European Journal of Medicinal Chemistry, 44, 3645-3653. https://doi.org/10.1016/j.ejmech.2009.02.021 DOI: https://doi.org/10.1016/j.ejmech.2009.02.021

Chikhale, R., Menghani, S., Babu, R., Bansode, R., Bhargavi, G., Karodia, N., Rajasekharan, M. V., Paradkar, A., & Khedekar, P. (2015). Development of selective DprE1 inhibitors. European Journal of Medicinal Chemistry, 96, 30-46. https://doi.org/10.1016/j.ejmech.2015.04.011 DOI: https://doi.org/10.1016/j.ejmech.2015.04.011

Drew, W. L., Barry, A. L., O’Toole, R., Sherris, J. C. (1972). Reliability of the Kirby-Bauer disc diffusion method for detecting methicillin-resistant strain of Staphylococcus aureus. Applied and Environmental Microbiology, 24(2), 240. https://doi.org/10.1128/am.24.2.240-247.1972 DOI: https://doi.org/10.1128/am.24.2.240-247.1972

Desai, N. C., Joshi, S. B., & Jadeja, K. A. (2020). A one-pot multicomponent Biginelli reaction for the preparation of novel pyrimidinthione derivatives as antimicrobial agents. Journal of Heterocyclic Chemistry, 57, 791-795. https://doi.org/10.1002/jhet.3821 DOI: https://doi.org/10.1002/jhet.3821

Deshmukh, M. B., Salunkhe, S. M., Patil, D. R., & Anbhule, P. V. (2009). A novel and efficient one-step synthesis of 2-amino-5-cyano-6-hydroxy-4-aryl pyrimidines and their antibacterial activity. European Journal of Medicinal Chemistry, 44(6), 2651-2654. https://doi.org/10.1016/j.ejmech.2008.10.018 DOI: https://doi.org/10.1016/j.ejmech.2008.10.018

Elumalai, K., Ali, M. A., Elumalai, M., Eluri, K., & Srinivasan, S. (2013). Design, synthesis and antimycobacterial activity of novel dihydropyrimidines. Journal of Pharmacy Research, 7(3), 241-245. https://doi.org/10.1016/j.jopr.2013.03.016 DOI: https://doi.org/10.1016/j.jopr.2013.03.016

El-Sayed, I. W. A., Zeid, F., Morsi, E. M., Tawfek, N., Yousif, N. M., Yahia, S., & Abdel-Rahman, A. A. H. (2015). Synthesis and anticancer activity of new substituted pyrimidines. Life Science Journal, 12, 63-70.

Falsone, F. S., & Kappe, C. O. (2001). The Biginelli dihydroprimidone synthesis using polyphosphate ester as a mild and efficient cyclocondensation/dehydration reagent. Arkivoc, 122-134. DOI: https://doi.org/10.3998/ark.5550190.0002.214

Fang, Z., & Lam, Y. (2011). A rapid and convenient synthesis of 5-unsubstituted 3,4-dihydropyrimidin-2-ones and thiones. Tetrahedron, 67, 1294-1297. https://doi.org/10.1016/j.tet.2010.11.075 DOI: https://doi.org/10.1016/j.tet.2010.11.075

Fischer, E., & Koch, H. (1886). Ueber einige derivate des Trimethylen- und Aethylendiamins. In: Bergmann, M. (eds). Untersuchungen aus Verschiedenen Gebieten, 232(2), 222-228. https://doi.org/10.1007/978-3-642-51364-0_31 DOI: https://doi.org/10.1002/jlac.18862320211

Frutos, R. P., Wei, X., Patel, N. D., Tampone, T. G., Mulder, J. A., Busacca, C. A., & Senanayake, C. H. (2013). One-pot synthesis of 2,5-disubstituted pyrimidines from nitriles. The Journal of Organic Chemistry, 78(11), 5800-5803. https://doi.org/10.1021/jo400720p DOI: https://doi.org/10.1021/jo400720p

Fustero, S., Catalan, S., Acena, J. L., & del Pozo, C. (2009). A new strategy for the synthesis of fluorinated 3,4-dihydropyrimidinones. Journal of Fluorine Chemistry, 130(12), 1145-1150. https://doi.org/10.1016/j.jfluchem.2009.06.001 DOI: https://doi.org/10.1016/j.jfluchem.2009.06.001

Gayon, E., Szymczyk, M., Gérard, H., Vrancken, E., & Campagne, J. -M. (2012). Stereoselective and catalytic access to β-enaminones: An entry to pyrimidines. The Journal of Organic Chemistry, 77(20), 9205-9220. https://doi.org/10.1021/jo301675g DOI: https://doi.org/10.1021/jo301675g

Godhani, D. R., Dobariya, P. B., Jogel, A. A., Sanghani, A. M., & Mehta, J. P. (2014). An efficient synthesis, characterization, and antimicrobial screening of tetrahydropyrimidine derivatives. Medicinal Chemistry Research, 23, 2417-2425. https://doi.org/10.1007/s00044-013-0840-9 DOI: https://doi.org/10.1007/s00044-013-0840-9

Gordeev, F., Komkov, A. V., & Dorokhov, A. V. (1990). Synthesis of pyrimidines and pyrido[2,3-d] pyrimidines using N,S- and N,N-acetals of diacetyl ketene. Chemistry of Heterocyclic Compounds, 26(9), 1075-1076. https://doi.org/10.1007/BF00472498 DOI: https://doi.org/10.1007/BF00472498

Ghodasara, H. B., Trivedi, A. R., Kataria, V. P., Patel, B. G., & Shah, V. H. (2013). Synthesis and antimicrobial evaluation of novel substituted pyrimidine scaffold. Medicinal Chemistry Research, 22, 6121-6128. https://doi.org/10.1007/s00044-013-0596-2 DOI: https://doi.org/10.1007/s00044-013-0596-2

Ghosh, U., & Katzenellenbogen, J. A. (2009). A convenient method for the preparation of highly substituted pyrimidines: Synthesis of tri- and tetra-subsituted pyrimidines from 1,3-dicarbonyl compounds and N,N,N,-tris-(trimethylsilyl)amidines. Journal of Heterocyclic Chemistry, 39(5), 1101-1104 https://doi.org/10.1002/jhet.5570390542 DOI: https://doi.org/10.1002/jhet.5570390542

Grimaux, E. (1876). Annales de chimie, (5)11, 389.

Guo, W., Li, C., Liao, J., Ji, F., Liu, D., Wu, W., & Jiang, H. (2016). Transition metal free intermolecular direct oxidative C-N bond formation to polysubstituted pyrimidines. The Journal of Organic Chemistry, 81(13), 5538-46. https://doi.org/10.1021/acs.joc.6b00867 DOI: https://doi.org/10.1021/acs.joc.6b00867

Hantosh, A. M., Rajab, N. A., & Abachi, F. T. (2023). Synthesis, in silico ADMET, docking, antioxidant, antibacterial and antifungal evaluations of some pyrimidine derivatives. Journal of Medicinal and Pharmaceutical Chemistry Research, 5, 216-227.

Hassan, H. A., & Mohaisen, R. J. (2025). Design, synthesis and biological activity of pyrimidine derivatives of acetomido chalcone of crotamiton. Advanced Journal of Chemistry, Section A, 8, 1088-1105.

Himaja, M., Rout, P. K., Karigar, A. A., Poppy, D., Munirajasekhar, D. (2012). Synthesis and antioxidant activity of 4, 6–diphenylpyrimidin–2–amine and its derivatives. Universal Journal Of Pharmacy, 01(01), 72-77.

Holla, B.S., Rao, B. S., Sarojini, B., & Akberali, P. (2004). One pot synthesis of thiazolodihydropyrimidinones and evaluation of their anticancer activity. European Journal of Medicinal Chemistry, 39(9), 777-783. https://doi.org/10.1016/j.ejmech.2004.06.001 DOI: https://doi.org/10.1016/j.ejmech.2004.06.001

Holzer, M., Dobner, B., & Briel, D. (1994). Synthesis of N-Substituted Oxo- and Thioxopyrimidines from 1,2,4- Dithiazolium Salts. Liebigs Annalen der Chemie, 1994(9), 895-900. https://doi.org/10.1002/jlac.199419940909 DOI: https://doi.org/10.1002/jlac.199419940909

Hu, M., Wu, J., Zhang, Y., Qiu, F., & Yu, Y. (2011). Synthesis of polysubstituted 5-aminopyrimidines from α-azidovinyl ketones and amidines. Tetrahedron, 67(14), 2676-2680. https://doi.org/10.1016/j.tet.2011.01.062 DOI: https://doi.org/10.1016/j.tet.2011.01.062

Jadhav, S. D., & Singh, A. (2017). Oxidative annulations involving DMSO and formamide. Organic Letters, 19(20), 5673-5676. https://doi.org/10.1021/acs.orglett.7b02838 DOI: https://doi.org/10.1021/acs.orglett.7b02838

Jogula, A. K., Chellapalli, S., & Pendem, H. B. (2011). One pot synthesis of dihydropyrimidinones catalyzed by Cyanuric chloride. Der Pharma Chemica, 3(4), 292-297.

Kachroo, M., Panda, R., & Yadav, Y. (2014). Synthesis and biological activities of some new pyrimidine derivatives from chalcones. Der Pharma Chemica, 6(2), 352-359.

Katritzky, A. R., Soloducho, J., & Belyakov, S. (2000). Bis-4-halophenyl-pyrimidines and -1,2,4,5-tetrazines, Arkivoc, 1, 37-42. DOI: https://doi.org/10.3998/ark.5550190.0001.106

Kiselyov, A. S. (2005). One-pot synthesis of polysubstituted pyrimidines. Tetrahedron Letters, 46(10), 1663-1665. https://doi.org/10.1016/J.TETLET.2005.01.068 DOI: https://doi.org/10.1016/j.tetlet.2005.01.068

Lewis, A., & Rosenbach, V. (1981). A novel convenient one step pyrimidine synthesis. Tetrahedron Letters, 22(15), 1453-1454. https://doi.org/10.1016/S0040-4039(01)90348-X DOI: https://doi.org/10.1016/S0040-4039(01)90348-X

Li, N., Chen, X.-H., Song, J., Luo, S.-W., Fan, W., & Gong, L.-Z. (2009). Highly enantioselective organocatalytic Biginelli and Biginelli-like condensations. Journal of the American Chemical Society, 131(42), 15301-15310. https://doi.org/10.1021/ja905320q DOI: https://doi.org/10.1021/ja905320q

Heravi, M. M., Sadjadi, S., Hossein, H. A., Shoar, R. H., & Bamoharram, F. F. (2009). A direct oxidative route for the synthesis of pyrimidines using heteropolyacids. Tetrahedron Letters, 50(6), 662-666. https://doi.org/10.1016/j.tetlet.2008.11.105 DOI: https://doi.org/10.1016/j.tetlet.2008.11.105

Lillo, V. J., Mansilla, J., & Saá, J. M. (2016). Organocatalysis by networks of cooperative hydrogen bonds. Angewandte Chemie, 128(13), 4384-4388. https://doi.org/10.1002/anie.201511555 DOI: https://doi.org/10.1002/ange.201511555

Malik, A. A., Dangroo, N. A., & Ara, T. (2020). Microwave-assisted tandem Kornblum oxidation and Biginelli reaction for the synthesis of dihydropyrimidones. ChemistrySelect, 5, 12965-12970. https://doi.org/10.1002/slct.202002864 DOI: https://doi.org/10.1002/slct.202002864

Masquelin, T., Sprenger, D., Baer, R., Gerber, F., & Mercadal, Y. (1998). A novel solution- and solid-phase approach to 2.4.5-tri- and 2.4.5.6-tetrasubstituted pyrimidines and their conversion into condensed heterocycles. Helvetica Chimica Acta, 81(3-4), 646-660. https://doi.org/10.1002/hlca.19980810315 DOI: https://doi.org/10.1002/hlca.19980810315

Mathews, A., & Asokan, C. V. (2007). Synthesis of pyrimidine-5-carbaldehydes from α-formylaroylketene dithioacetals. Tetrahedron, 63(33), 7845-7849. https://doi.org/10.1016/j.tet.2007.05.098 DOI: https://doi.org/10.1016/j.tet.2007.05.098

Medina-Mercado, I., Zaragoza-Galicia, I., Olivo, H. F., & Romero-Ortega, M. (2018). 2-Trifluoromethyl-1,3-diazabutadienes for the construction of 2-trifluoromethylpyrimidine derivatives. Synthesis, 50, 4133-4139. https://doi.org/10.1055/s-0037-1610444 DOI: https://doi.org/10.1055/s-0037-1610444

Mehta, H., & Khunt, R. (2014-2015). Synthesis and studies of some substituted pyrimidines. International Journal of ChemTech Research, 7(01), 275-278.

Movassaghi, M., & Hill, M. D. (2006). Single-step synthesis of pyrimidine derivatives. Journal of the American Chemical Society, 128(44), 14254-14255. https://doi.org/10.1021/ja066405m DOI: https://doi.org/10.1021/ja066405m

Nagahara, U., Kawano, H., Sasaoka, S., Ukawa, C., Hirama, T., Takada, A., Cottam, H. B., & Robins, R. K. (1994). Reaction of 5-aminopyrazole derivatives with ethoxymethylene-malononitrile and its analogues. Journal of Heterocyclic Chemistry, 31(1), 239-243. DOI: https://doi.org/10.1002/jhet.5570310140

Nerkar, A. U. (2021). Use of pyrimidine and its derivative in pharmaceuticals: A review. Journal of Advanced Chemical Sciences, 729-732. DOI: https://doi.org/10.30799/jacs.239.21070203

Nikam, D., Jain, A., Vetale, A., Bhange, A., & Jadhav, S. (2024). Synthesis and evaluation of novel thiophene-dhpms. Current Chemistry Letters, 13(4), 717-724. https://doi.org/10.5267/j.ccl.2024.4.002 DOI: https://doi.org/10.5267/j.ccl.2024.4.002

Nilsson, B., & Overman, L. (2006). Concise synthesis of guanidine-containing heterocycles using the Biginelli reaction. The Journal of Organic Chemistry, 71(20), 7706-7714. https://doi.org/10.1021/jo061199m DOI: https://doi.org/10.1021/jo061199m

Qu, H., Li, X., Mo, F., & Lin, X. (2013). Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction. Beilstein Journal of Organic Chemistry, 9, 2846-2851. https://doi.org/10.3762/bjoc.9.320 DOI: https://doi.org/10.3762/bjoc.9.320

Taylor, E. C., Knopf, R. J., Meyer, R. F., Holmes, A., & Hoefle, M. L. (1960). Pyrimido [4,5-d]pyrimidines. Part I. Journal of the American Chemical Society, 82(21), 5711. https://doi.org/10.1021/ja01506a038 DOI: https://doi.org/10.1021/ja01506a038

Tolba, M., El-Dean, A., Ahmed, M., Hassanien, R., Sayed, M., Zaki, R., Mohamed, S., Zawam, S., & Abdel-Raheem, S. (2022). Synthesis, reactions, and applications of pyrimidine derivatives. Current Chemistry Letters, 11, 121-138. DOI: https://doi.org/10.5267/j.ccl.2021.8.002

Pews, R. G. (1988). Synthesis of 2-Alkylpyrimidines via 2-Alkyl-1,4,5,6-tetrahydropyrimidines. Heterocycles, 27(8), 1867-1873. DOI: https://doi.org/10.3987/COM-88-4530

Pinner, A. (1884). Ueber die Einwirkung von Acetessigäther auf die Amidine. Berichte der Deutschen Chemischen Gesellschaft, 17(2), 2519-2526. https://doi.org/10.1002/cber.188401702173 DOI: https://doi.org/10.1002/cber.188401702173

Rao, G. B. D., Acharya, B. N., Verma, S. K., & Kaushik, M. P. N,N’ -Dichlorobis(2,4,6-trichlorophenyl)urea (CC-2) as a new reagent for the synthesis of pyrimidone and pyrimidine derivatives via Biginelli reaction. Tetrahedron Letters, 52(7), 809-812. https://doi.org/10.1016/j.tetlet.2010.12.039 DOI: https://doi.org/10.1016/j.tetlet.2010.12.039

Raval, C. C., Sharma, B. M., Mehta, H., & Rojiwadiya, A. J. (2012). Synthesis of substituted pyrimidine derivatives and evaluation of their antimicrobial activity. RJPBCS, 3(3), 57.

Shehab, W. S., Assy, M. G., Moustafa, H. Y., Abdellattif, M. H., & Rahman, H. M. A. (2019). Pyrimidines as block units in heterocycles. Journal of the Iranian Chemical Society, 16. https://doi.org/10.1007/s13738-019-01712-4 DOI: https://doi.org/10.1007/s13738-019-01712-4

Sheibani, H., Saljoogi, A. S., & Bazgir, A. (2008). Three-component process for the synthesis of 4-amino-5- pyrimidinecarbonitriles under thermal aqueous conditions or microwave irradiation. Archive for Organic Chemistry, 2008(2), 115-123. https://doi.org/10.3998/ark.5550190.0009.213 DOI: https://doi.org/10.3998/ark.5550190.0009.213

Sheibani, H., Seifi, M., & Bazgir, A. (2009). Three-component synthesis of pyrimidine and pyrimidinone derivatives in the presence of high-surface-area MgO. Synthetic Communications, 39(6), 1055-1064. https://doi.org/10.1080/00397910802474982 DOI: https://doi.org/10.1080/00397910802474982

Singh, B. D., Pandey, J., Khanam, H., & Singh, S. (2022). Lewis acid catalyzed [3+3] annulation/aldol condensation in water. Asian Journal of Organic Chemistry, 11(11), e202200479. https://doi.org/10.1002/ajoc.202200479 DOI: https://doi.org/10.1002/ajoc.202200479

Sridhar, Y., Prasad, R., & Dinda, S. C. (2011). Synthesis and anticancer activity of some novel pyrimidine derivatives. IJPSR – International Journal of Pharmaceutical Sciences and Research, 2(10), 2562-2565.

Stucchi, M., Lesma, G., Meneghetti, F., Rainoldi, G., Sacchetti, A., & Silvani, A. (2016). Organocatalytic asymmetric Biginelli-like reaction involving isatin. The Journal of Organic Chemistry, 81(5), 1877-1884. https://doi.org/10.1021/acs.joc.5b02680 DOI: https://doi.org/10.1021/acs.joc.5b02680

Sośnicki, J. C., Struk, L., Kurzawski, M., Perużyńska, M., Maciejewska, G., & Droździk, M. (2014). Regioselective synthesis of novel 4,5-diaryl functionalized 3,4-dihydropyrimidine-2(1H)-thiones. Organic & Biomolecular Chemistry, 12(21), 3427-3440. https://doi.org/10.1039/c4ob00094c DOI: https://doi.org/10.1039/c4ob00094c

Suryawanshi, S. N., Kumar, S., Tiwari, A., Shivahare, R., Chhonker, Y. S. (2013). Synthesis and biological evaluation of a novel series of aryl S, N-ketene acetals as antileishmanial agents. Bioorganic & Medicinal Chemistry Letters, 23(13), 3979-3982. https://doi.org/10.1016/j.bmcl.2013.04.025 DOI: https://doi.org/10.1016/j.bmcl.2013.04.025

Timoshenko, V. M., Markitanov, Y. M., Salimov, Y. O., & Shermolovich, Y. G. (2014). 2-Oxo-2-polyfluoroalkylethane-1-sulfones and -sulfamides in the three-component reactions leading to pyrimidine derivatives. Arkivoc, 86-107. DOI: https://doi.org/10.3998/ark.5550190.p008.582

Tripathi, S., Singh, R., Kumar, D., Kumar, J., & Singh, U. (2022). Synthesis, characterization and antimicrobial evaluation of some pyrimidine derivatives. Indo American Journal of Pharmaceutical Sciences, 09(11), 234-241. https://doi.org/10.5281/zenodo.7421235

Verma, V., Joshi, C. P., Agarwal, A., Soni, S., & Kataria, U. (2020). A review on pharmacological aspects of pyrimidine derivatives. Journal of Drug Delivery and Therapeutics, 10, 358-361. DOI: https://doi.org/10.22270/jddt.v10i5.4295

Viveka, S., Madhu, L. N., & Nagaraja, G. K. (2015). Synthesis of new pyrazole derivatives via multicomponent reaction and evaluation of their antimicrobial and antioxidant. Monatshefte für Chemie – Chemical Monthly, 146, 1547-1555. https://doi.org/10.1007/s00706-015-1428-5 DOI: https://doi.org/10.1007/s00706-015-1428-5

Vora, J., & Vyas, K. (2019). Synthesis and biological evaluation of some abbreviated new pyrimidine derivatives. IJSRST, 6(3), 354-361. https://doi.org/10.32628/IJSRST1207250 DOI: https://doi.org/10.32628/IJSRST1207250

Wan, J.-P., Lin, Y., Hu, K., & Liu, Y. (2014). Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones. Beilstein Journal of Organic Chemistry, 10, 287-292. https://doi.org/10.3762/bjoc.10.25 DOI: https://doi.org/10.3762/bjoc.10.25

Wang, Z. W., Zheng, Y., Qian, Y. E., Guan, J. P., Lu, W. D., Yuan, C. P., Xiao, J. A., Chen, K., Xiang, H. Y., & Yang, H. Photoredox-catalyzed cascade of o-hydroxyarylenaminones to access 3-aminated chromones. The Journal of Organic Chemistry, 87(2), 1477-1484. https://doi.org/10.1021/acs.joc.1c02796 DOI: https://doi.org/10.1021/acs.joc.1c02796

Wendelin, W., Schermanz, K., Schweiger, K., & Fuchsgruber, A. (1983). Über die Reaktionen von monosubstituierten Guanidinen mit 1-Phenyl-1,3-butandion. Monatshefte für Chemie, 114, 1371-1379. https://doi.org/10.1007/BF00798647 DOI: https://doi.org/10.1007/BF00798647

Yadlapalli, R. K., Chourasia, O. P., Vemuri, K., Sritharan, M., & Perali, R.S. (2012). Synthesis and in vitro anticancer and antitubercular activity of diarylpyrazole ligated dihydropyrimidines. Bioorganic & Medicinal Chemistry Letters, 22(8), 2708-2711. https://doi.org/10.1016/j.bmcl.2012.02.101 DOI: https://doi.org/10.1016/j.bmcl.2012.02.101

Yavuz, S. Ç., Akkoç, S., Türkmenoglu, B., & Sarıpınar, E. (2020). Synthesis of novel heterocyclic compounds containing pyrimidine nucleus using the Biginelli reaction. Journal of Heterocyclic Chemistry, 57(6), 2615-2627. https://doi.org/10.1002/jhet.3978 DOI: https://doi.org/10.1002/jhet.3978

Yavuz, S. Ç., Akkoç, S., Tüzün, B., Şahin, O., & Saripinar, E. (2021). Efficient synthesis and molecular docking studies of new pyrimidine-chromeno hybrid derivatives. Synthetic Communications, 51(14), 2135-2159. https://doi.org/10.1080/00397911.2021.1922920 DOI: https://doi.org/10.1080/00397911.2021.1922920

Ye, J., Li, G., Wan, C., Wan, J-P. (2026). Chalcogen functionalized pyrimidine synthesis by three-component free radical chalcogenation. Organic Chemistry Frontiers, 13, 106-111. https://doi.org/10.1039/D5QO01206F DOI: https://doi.org/10.1039/D5QO01206F

Yu, Q., Liu, Y., & Wan, J. P. (2020). Transition metal-free synthesis of 3-trifluoromethyl chromones via enaminones. Organic Chemistry Frontiers, 7(18), 2770-2775. https://doi.org/10.1039/D0QO00855A DOI: https://doi.org/10.1039/D0QO00855A

Yuan, J., Li, J., Wang, B., Sun, S., & Cheng, J. (2017). Base-promoted formal [4+1+1] annulation of aldehyde, N-benzyl amidine and DMSO toward 2,4,6-triaryl pyrimidines. Tetrahedron Letters, 58(51), 4783-4785. https://doi.org/10.1016/j.tetlet.2017.11.020 DOI: https://doi.org/10.1016/j.tetlet.2017.11.020

Zaied, A. M. (2018). Synthesis and characterization of some Novel Heterocyclic Compounds of Pyrimidine and pyrazole from Chalcone derivatives. AL-Qadisiyah Journal of Pure Science, 23, 141. DOI: https://doi.org/10.29350/jops.2018.23.2.747

Zarenezhad, E., Farjam, M., & Iraji, A. (2021). Synthesis and biological activity of pyrimidines containing hybrids. Journal of Molecular Structure, 1230, 129833. https://doi.org/10.1016/j.molstruc.2020.129833 DOI: https://doi.org/10.1016/j.molstruc.2020.129833

Zhichkin, P., Fairfax, D. J., & Eisenbein, S. A. (2022). A general procedure for the synthesis of 2-substituted pyrimidine-5-carboxylic esters. Synthesis, 720-722. https://doi.org/10.1055/s-2002-25767 DOI: https://doi.org/10.1055/s-2002-25767

Downloads

Published

2026-06-17

How to Cite

Rahman, M. M., Reza, A. F. G. M., Hossain, M. L., Rahman, A. K. M. L., & Islam, R. (2026). Metal-free, acid-base, and organocatalyst-promoted semi-green protocols for the efficient construction of structurally diverse & highly functionalized pyrimidine derivatives: A long-term review (1876–2026). Brazilian Journal of Science, 5(8), 52–91. https://doi.org/10.14295/bjs.v5i8.898

Similar Articles

<< < 7 8 9 10 11 12 13 14 > >> 

You may also start an advanced similarity search for this article.