Sains Malaysiana 53(4)(2024): 839-850

http://doi.org/10.17576/jsm-2024-5304-09

Synthesis and Characterization of Hexahydropyrimidines and Their New Derivatives

(Sintesis dan Pencirian Heksahidropirimidina serta Terbitan Baharunya)

SHUKKUR A. HAMED¹, ATHRAA THAKER¹, BILAL MAJID RUDAINI², HASANAIN SALAH NAEEM³, MUNTAZ ABU BAKAR⁴ & SITI AISHAH HASBULLAH^4,*

¹Department of Chemistry, College of Education for Pure Science, University of Anbar, Al-Anbar, Iraq

²Department of Pharmacy, Al-Maarif University College, Al Anbar,31001, Iraq

³Faculty of Pharmacy, University of Al Muthanna, Samawah 66001, Iraq

⁴Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor 43600, Malaysia

Diserahkan: 8 September 2023/Diterima: 29 Februari 2024

Abstract

Three new hexahydropyrimidine derivatives 1a – 1c were successfully synthesized using the Mannich-type reaction. Furthermore, the synthesis of three amino bases 2a – 2c was achieved through the reduction reaction of pyrimidine compounds using hydrazine, followed by the substitution reaction of nitro groups at diverse positions. Subsequently, one of the synthesized amino base derivatives 2c underwent conversion into seven Schiff bases 3a – 3g via a condensation reaction involving the aforementioned amino base derivative and a selection of benzaldehyde derivatives. Four amide compounds 4a – 4d have been synthesized by a reaction of the secondary amine group in the pyrimidine ring with benzoyl chloride. The products were subjected to comprehensive characterization employing rigorous analytical techniques, including FT-), ¹H-NMR (Proton Nuclear Magnetic Resonance Spectroscopy), and LC-MS (Liquid Chromatography–Mass Spectrometry). Additionally, the Molecular Electrostatic Potential (MEP) study was carried out to further investigate the properties of the synthesized compounds. The yields of the three methods used to synthesise new hexahydropyrimidine derivatives varied depending on the specific substituents added to the aromatic ring.

Keywords: Hexahydropyrimidine; Mannich-type reaction; Molecular Electrostatic Potential; Schiff-Bases

Abstrak

Sebanyak tiga terbitan heksahidropirimidin 1a – 1c telah berjaya disintesis menggunakan tindak balas jenis-Mannich. Selain itu, sintesis tiga bes amino 2a – 2c telah berjaya dijalankan melalui tindak balas penurunan sebatian pirimidina menggunakan sebatian hidrazina, diikuti oleh tindak balas penukargantian oleh kumpulan nitro pada posisi berlawanan. Sebatian 2c telah ditukarkan kepada tujuh bes Shiff 3a – 3g melalui tindak balas kondensasi melibatkan terbitan bes amino dan terbitan benzaldehid terpilih. Empat sebatian amida 4a – 4d telah disintesis melalui tindak balas kumpulan amina sekunder pada gelang pirimidina dengan benzoil klorida. Hasil kemudian dicirikan secara komprehensif melibatkan kepelbagaian teknik termasuk FT-IR (Spektroskopi Inframerah Fourier Transform), ¹H-NMR (1H-Spektroskopi Nuklear Magnetik Resonan) dan LC-MS (Cecair Kromatografi–Spektrometri Jisim). Tambahan pula, kajian Potensi Elektrostatik Molekular (MEP) telah dijalankan untuk mengkaji dengan lebih mendalam ciri sebatian yang disintesis. Hasil yang diperoleh daripada tiga kaedah berbeza daripada sintesis sebatian baharu terbitan heksahidropirimidina menunjukkan variasi bergantung kepada penukarganti pada gelang aromatik.

Kata kunci: Bes-Schiff; heksahidropirimidina; Potensi Elektrostatik Molekul; tindak balas jenis Mannich

RUJUKAN

Ahmed, S.M., Salih, K.M., Ahmad, H.O., Jawhar, Z.H. & Hamad, D.H. 2019. Synthesis, spectroscopic characterization and antibacterial activity of new series of Schiff base derived from 4-aminoantipyrine and 2-amino benzimidazole. Zanco Journal of Medical Sciences 23(2): 206-216.

Athraa, T. & Shukkur, A.H. 2021. A newly synthesis and identification of 5-nitro-2, 4, 6-triphenyl hexahydro pyrimidine derivatives structures. Turkish Journal of Physiotherapy and Rehabilitation 32(3): 8596-8606.

Bolduc, A., Rivier, L., Dufresne, S. & Skene, W.G. 2012. Spectral investigation of conjugated azomethines: A large palette of colors possible with acid and oxidant doping. Materials Chemistry and Physics 132(2-3): 722-728.

Cantillo, D., Moghaddam, M.M. & Kappe, C.O. 2013. Hydrazine-mediated reduction of nitro and azide functionalities catalyzed by highly active and reusable magnetic iron oxide nanocrystals. The Journal of Organic Chemistry 78(9): 4530-4542.

Cantillo, D., Baghbanzadeh, M. & Kappe, C.O. 2012. In situ generated iron oxide nanocrystals as efficient and selective catalysts for the reduction of nitroarenes using a continuous flow method. Angewandte Chemie 124(40): 10337-10340.

Feng, J., Handa, S., Gallou, F. & Lipshutz, B.H. 2016. Safe and selective nitro group reductions catalyzed by sustainable and recyclable Fe/ppm Pd nanoparticles in water at room temperature. Angewandte Chemie 128(31): 9125-9129.

Goyal, M., Kumar, S., Bahadur, I., Verma, C. & Ebenso, E.E. 2018. Organic corrosion inhibitors for industrial cleaning of ferrous and non-ferrous metals in acidic solutions: A review. Journal of Molecular Liquids 256: 565-573.

Hakiri, R., Ameur, I., Abid, S. & Derbel, N. 2018. Synthesis, X-ray structural, Hirshfeld surface analysis, FTIR, MEP and NBO analysis using DFT study of a 4-chlorobenzylammonium nitrate (C₇ClH₉N)⁺(NO₃)^–. Journal of Molecular Structure 1164: 486-492.

Hamed, S.A. 2020. A novel synthesis, molecular structure by x-ray diffraction of 5-nitro-2,4,6- triphenylhexahydropyrimidine, and some it’s derivatives. Systematic Reviews in Pharmacy 11(12): 1838-1847. doi:10.31838/srp.2020.12.279

Jezuita, A., Ejsmont, K. & Szatylowicz, H. 2021. Substituent effects of nitro group in cyclic compounds. Structural Chemistry 32(1): 179-203.

Kasimala, M. 2021. Synthesis of Schiff bases: A Glimpse on recent literature. Caribbean Journal of Sciences and Technology 9(1): 7-9.

Khan, S.A., Ullah, Q., Almalki, A.S.A., Kumar, S., Obaid, R.J., Alsharif, M.A., Alfaifi, S.Y. & Hashmi, A.A. 2021. Synthesis and photophysical investigation of (BTHN) Schiff base as off-on Cd²⁺ fluorescent chemosensor and its live cell imaging. Journal of Molecular Liquids 328: 115407.

Leggio, A., Bagalà, J., Belsito, E.L., Comandè, A., Greco, M. & Liguori, A. 2017. Formation of amides: one-pot condensation of carboxylic acids and amines mediated by TiCl₄. Chemistry Central Journal 11: 87.

Li, Y., Wang, Y. & Wang, J. 2008. Microwave-assisted synthesis of amides from various amines and benzoyl chloride under solvent-free conditions: A rapid and efficient method for selective protection of diverse amines. Russian Journal of Organic Chemistry 44(3): 358-361.

Orlova, N., Nikolajeva, I., Pučkins, A., Belyakov, S. & Kirilova, E. 2021. Heterocyclic schiff bases of 3-Aminobenzanthrone and their reduced analogues: Synthesis, properties and spectroscopy. Molecules 26(9): 2570.

Qin, W., Long, S., Panunzio, M. & Biondi, S. 2013. Schiff bases: A short survey on an evergreen chemistry tool. Molecules 18(10): 12264-12289.

Rai, R.K., Mahata, A., Mukhopadhyay, S., Gupta, S., Li, P-Z., Nguyen, K.T., Zhao, Y., Pathak, B. & Singh, S.K. 2014. Room-temperature chemoselective reduction of nitro groups using non-noble metal nanocatalysts in water. Inorganic Chemistry 53(6): 2904-2909.

Scrocco, E. & Tomasi, J. 1978. Electronic molecular structure, reactivity and intermolecular forces: An euristic interpretation by means of electrostatic molecular potentials. Advances in Quantum Chemistry 11: 115-193.

Shi, M., Ye, N., Chen, W., Wang, H., Cheung, C., Parmentier, M., Gallou, F. & Wu, B. 2020. Simple synthesis of amides via their acid chlorides in aqueous TPGS-750-M. Organic Process Research & Development 24(8): 1543-1548.

Tolba, M.S., Kamal El-Dean, A.M., Ahmed, M., Hassanien, R., Sayed, M., Zaki, R.M., Mohamed, S.K., Zawam, S.A. & Abdel-Raheem, S.A.A. 2022. Synthesis, reactions, and applications of pyrimidine derivatives. Current Chemistry Letters 11(1): 121-138.

Xian, L., Ma, C., Ouyang, Y., Di, J. & Zhang, Z. 2020. Synthesis of pyrimidine derivatives via multicomponent reaction catalyzed by ferric chloride. Applied Organometallic Chemistry 34(11): e5921.

Zarecki, A.P., Kolanowski, J.L. & Markiewicz, W.T. 2020. Microwave-assisted catalytic method for a green synthesis of amides directly from amines and carboxylic acids. Molecules 25(8): 1761.

*Pengarang untuk surat-menyurat; email: aishah80@ukm.edu.my