Abstract
Recent advancements in synthesizing Schiff bases, including sustainable and highly customizable approaches, are examined, offering insights into how their structures can be tailored for specific purposes. Schiff bases find applications in various fields, such as materials science, which contribute to developing polymers, metal-organic frameworks, nanocomposites, and medicinal chemistry, which serve as promising drug candidates. Additionally, they play crucial roles in coordination chemistry catalysis and have potential applications in emerging areas like nanotechnology and renewable energy, contributing to the development of nanomaterials and energy storage systems. This chapter provides a comprehensive overview of this synthesis and its applications, catering to researchers, students, and professionals looking to explore the multifaceted landscape of Schiff base compounds in contemporary organic chemistry.
Keywords
- Green chemistry
- pharmacological potential
- complex molecules
- condensation reactions
- primary amines
1. Introduction
The scientific community recently became fascinated by an intriguing group of versatile organic compounds known as Schiff bases [1, 2, 3]. These compounds, which originate from the condensation of primary amines with carbonyl compounds, are distinguished by a dynamic interplay of chemical properties supporting their diverse applications. This chapter is an in-depth look at the complex area of Schiff Base Chemistry [4, 5, 6]. It attempts to give a thorough analysis of the synthesis techniques and a broad picture of the numerous applications that have sprung from the latest developments in this exciting field. It is essential to comprehend Schiff bases’ historical roots to appreciate their contemporary relevance [7, 8, 9, 10]. Schiff bases have evolved dramatically since Hugo Schiff’s groundbreaking research in the late 1800s when he first described the condensation reaction between amines and aldehydes or ketones. Since their original discovery as synthetic intermediates, these substances have become adaptable building blocks with various functions. Revolutionary advancements in synthesizing Schiff bases have been made, indicating how organic chemistry constantly changes [10, 11, 12]. Green chemistry techniques, sonochemistry, and microwave-assisted synthesis are novel approaches that have enhanced conventional condensation reactions. Improving synthesis efficiency, these methods also correspond with the increasing focus on ecologically friendly and sustainable practices. These compounds’ versatility is highlighted by the fact that Schiff base synthesis can now use a wide range of starting materials, including heterocyclic compounds and unconventional amines [13, 14, 15].
Schiff bases are distinguished by their structural diversity, evidence of the abundant possibilities inherent in their chemistry. Researchers have deciphered the complex architectures of Schiff base compounds using sophisticated spectroscopic techniques like mass spectrometry, X-ray crystallography, and NMR spectroscopy [16, 17, 18, 19]. This structural realization makes understanding the relationship between molecular arrangement and properties possible, laying the groundwork for customizing Schiff bases for various uses. The emergence of Schiff bases as important participants in catalysis has greatly aided the development of effective and selective methods for organic synthesis. Schiff commands facilitate a spectrum of reactions by serving as ligands for transition metal catalysts, including oxidation, reduction, and cross-coupling [10, 20, 21, 22]. Changing the structure of the ligand allows for the modification of catalytic activity, which opens up new possibilities for synthesizing complex molecules with specific features. Schiff bases have emerged as an area of interest in medicinal chemistry due to their promising biological properties. Interest in using these substances for therapeutic purposes has increased due to their antimicrobial, antiviral, and anticancer characteristics. Structure-activity relationships are important in drug design because they have created hybrid compounds with improved pharmacological potential by combining Schiff bases with biologically active moieties [23, 24, 25].
The rich history, varied synthesis techniques, and plethora of applications of Schiff base chemistry become apparent as we progress through this chapter. There are many exciting developments and applications for Schiff bases, whose versatility inspires researchers to continue pushing the boundaries of chemical innovation. Join us as we explore the complexities of Schiff base chemistry and its revolutionary influence on modern organic chemistry, as scientists and enthusiasts are invited to participate (Figure 1).
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F1.png)
Figure 1.
Recently developed Schiff bases have found significant applications in therapeutics.
2. Synthesis of unique Schiff bases and their applications
Ashraf S. Hassan, in 2023, a novel scientific finding [26], has demonstrated the possibility of a successful “one drug—multiple targets” strategy for treating complex medical conditions. 3-hydrazino-isatin was reacted with different aldehydes to form novel derivatives of isatin-based Schiff bases (2–7). Extensive
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F2.png)
Figure 2.
Synthesis and production of Isatin-Centered azomethine and Isatin-Centered azomethine-arylazo compounds.
In 2022, Maryam Fawzi Habeeb created N-anthranilic acid [27] by starting the process with the Ullmann reaction, which involved combining derivatives of o-chlorobenzoic acid with o- and p-phenylenediamine. These compounds were cyclized using poly(phosphoric acid) (PPA) to produce products of amino acridone. The next step was to create terphthaldehyde mono Schiff bases by reacting terphthaldehyde with panisidine, o-, m-, or p-toluidine. These were then mixed with the derivatives of amino acridone to form additional Schiff bases. Different compounds were produced by the amino acridone derivatives reacting independently with terphthaldehyde, 4-(dimethyl amino) benzaldehyde, 2-formyl benzoic acid, and methyl-4-formyl benzoate. The structural characterization was done using FTIR spectroscopy, 13C NMR, and 1H NMR. The synthesized products demonstrated potential applications in medicinal chemistry and antibacterial research, as demonstrated by their antibacterial efficacy tests against
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F3.png)
Figure 3.
Investigations into the creation, properties, and biological functions of new Schiff bases from amino acridone.
Marijana Hranjec’s study from 2023 explores [28, 29] the antiviral, antibacterial, and antiproliferative properties of novel Schiff bases made from benzimidazoles that have been N-substituted. The study examines the nature of substituents at the N atom of benzimidazole nuclei and their impact on the phenyl ring. The research uses
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F4.png)
Figure 4.
Schiff bases derived from N-substituted benzimidazole: Design and synthesis: Exploring novel antimicrobial agents.
Nazish Shahab [29], successfully synthesized in three steps a series of novel Schiff’s base hydrazone derivatives (1–24) based on polyhydroquinoline (PHQ) with good yields. Refluxing ethyl-2-(2-formylphenoxy)acetate, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol for 6-7 hours produced the first compound (1). This was carried out in an unsymmetrical multi-component one-pot Hantzsch reaction. Compound 2 refluxed the resultant PHQ for 4–5 hours in absolute ethanol with hydrazine hydrate. The hydrazide was treated with various substituted aromatic/aliphatic aldehydes for the production of Schiff bases (3–24). Structural analysis was performed on all synthesized analogs using 1H, 13C, and LC-HRESI-MS spectroscopy. With IC50 values ranging from 5.26 to 25.17 μM, 12 compounds (10, 14, 7, 9, 8, 17, 12, 19, 13, 15, 21, and 11) demonstrated significant activity against α-glucosidase. The move was higher than that of acarbose, which has an IC50 of 873.34 ± 1.67 μM, a standard α-glucosidase inhibitor. Molecular docking studies demonstrated that these active compounds efficiently occupied the α-glucosidase acarbose binding pocket, suggesting their potential as α-glucosidase inhibitors (Figure 5).
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F5.png)
Figure 5.
Characterization and synthesis of novel hydrazone Schiff Base derivatives based on Polyhydroquinoline nucleus: Potential antioxidants and antibacterial agents.
According to Najiah M. Alyamani, organic compounds’ structural [1] symmetry or asymmetry is one of their most fundamental characteristics. Z-geometrical isomers are kinetically preferred, promiscuous structures with many biological functions. Beginning with the ethyl acrylate ester derivative (Z)-1 starting material, a new series of hybrid molecules containing 3,4,5-trimethoxybenzamide moieties and Schiff base were synthesized, and elemental microanalysis, 1H-NMR, and 13C-NMR spectroscopic studies were used to confirm their structural integrity. Colchicine was the reference material, and the MCF-7 breast cancer line was used as a test subject for the target hybrids’
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F6.png)
Figure 6.
Optimized synthetic routes for the design and elaboration of Schiff Base–TMB derivatives.
As per Shahnazar Ali, in 2023, a novel class of thiazolidinones (TZD 5a-s) and azetidinones (AZT 6a-s) was developed, with their target being [2] the cox-2 enzyme (PDB protein 1PXX). 2-mercapto benzoxazole (1) was used as the starting material in conventional and microwave methods. The rat paw edema method was used to measure the anti-inflammatory activity
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F7.png)
Figure 7.
Design and synthesis of benzoxazole-substituted Thiazolidinones and Azetidinones.
In February 2023, Kiran Singh and his team produced a novel [30] Schiff base known as five-methyl-3-((5-bromosalicylidene) amino)-pyrazole (HMBP) by refluxing 3-amino-5-methylpyrazole and 5-bromosalicylaldehyde in methanol at a 1:1 M constitution. Elemental analysis and spectral techniques (1 H NMR, IR, and mass) were used to characterize the HMBP. The coordination behavior of certain transition metal ions with newly synthesized Schiff base is also described. 1H NMR, fluorescence, elemental analyses, infrared spectra, electronic spectra, UV–vis, mass, and magnetic moments have all been used to characterize the complexes. The thermogravimetric assay (TG-DTG) has been used to conduct and explain the thermal study of the complexes. T Infrared spectra show that the Schiff base is a bidentate ligand linked to the metal ions by protonated phenolic O and imine N. The presence of water molecules is confirmed by thermal analysis. Quantum yields were measured in addition to the HMBP and all metal complexes’ determined structures. According to a fluorescence study, metal complexes exhibit more intense fluorescence than the new Schiff base. To calculate the kinetics variables, the Coats-Redfern equation was applied. A variety of food-borne pathogens, such as Clostridium perfringens (MTCC 450), Escherichia coli (MTCC 433), Staphylococcus aureus sub aureus (MTCC 1144), Pseudomonas aeruginosa (MTCC 424), and fungi (Aspergillus niger, Aspergillus fumigatus, and Candida albicans), were tested against the synthesized ligand and its complexes. All of the complexes were found to have stronger biological activity toward individual organisms when compared to the new Schiff base (Figure 8).
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F8.png)
Figure 8.
Extensive studies on the synthesis of new Schiff Base 5-Methyl-3-((5-Bromosalicylidene) amino)-pyrazole and its transition metal complexes.
In June 2022, Sheikh Abdul Majid’s Schiff bases were [31] recognized as essential chemical scaffolds for applications in both industry and medicine. Because carbamate derivatives have so many uses, we report here the synthesis and characterization of a new Schiff base ligand, (E)-ethyl 2-(4 methoxy benzylidene) hydrazine carboxylate, and 4-(nitrobenzaldehyde) methylcarbamate. The compound was characterized by combining B3LYP and 6-31 G(d,p)formalism with calculations from density functional theory and experimental data. The primary characterization techniques used for the elemental analysis of the mixture were FT-IR, UV-Vis, and NMR spectroscopic evaluations (Figure 9).
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F9.png)
Figure 9.
Design and synthesis of Carbazate derivatives as innovative Schiff Base ligands for advanced coordination chemistry.
In 2023, Nandeshwarappa utilized condensation synthesis [32] to generate a sequence of (E)-1-methyl-3-((substituted phenylamino)methyl) quinoline-2(1H)-one Schiff bases (3a-j) containing the quinoline moiety (2a-j) from a solitary starting material, 1-methyl-2-oxo-1,2-dihydroquinoline-3-carbaldehyde (1). The structure of the recently synthesized compounds was verified by Fourier transformation infrared (FTIR), mass spectroscopy, elemental analysis, and proton (1H) and carbon (13C) nuclear magnetic resonance spectroscopy. The
![](http://cdnintech.com/media/chapter/88818/1724837355-636712039/media/F10.png)
Figure 10.
Convenient synthesis, characterization, and biological evaluation of novel Schiff Base heterocycles.
3. Conclusion
In conclusion, investigating advances in Schiff base chemistry has shed light on the field’s dynamic evolution and potential to have a revolutionary effect in modern chemistry. The experience has highlighted structural adaptability, creative synthetic approaches, and a wide range of uses for Schiff bases in fields such as medicinal chemistry and materials science. Schiff bases will significantly impact the direction of environmentally friendly and sustainable chemistry as we look toward the future. Their potential in cutting-edge fields like supramolecular chemistry, nanotechnology, and renewable energy sources offers intriguing chances for additional study and development. To help researchers and enthusiasts navigate this dynamic and exciting field of organic chemistry, the chapter has attempted to provide a comprehensive understanding of Schiff base chemistry.
References
- 1.
Alyamani NM. New schiff base–tmb hybrids: design, synthesis and antiproliferative investigation as potential anticancer agents. Symmetry. 2023; 15 :609 - 2.
Ali S, Omprakash P, Tengli AK, Mathew B, Basavaraj MV, Parkali P, et al. Synthesis of Novel Benzoxazole Derivatives: Exploration of Their Possible Pharmacological Profiles with Computational Studies. Polycyclic Aromatic Compounds. 2023; 43 :3853-3886 - 3.
Amirkhanov V, Rauf A, Hadda TB, Ovchynnikov V, Trush V, Saleem M, et al. Pharmacophores modeling in terms of prediction of theoretical physicochemical properties and verification by EXPERIMENTAL correlations of carbacylamidophosphates (CAPh) and sulfanylamidophosphates (SAPh) tested as new carbonic anhydrase inhibitors. Mini Reviews in Medicinal Chemistry. 2019; 19 :1015-1027 - 4.
Raczuk E, Dmochowska B, Samaszko-Fiertek J, Madaj J. Different Schiff bases—structure, importance and classification. Molecules. 2022; 27 :787 - 5.
Ullah A, Liu J, Khan AU, Khan QU, Guo F, Nazir S, et al. Diversification and design of novel aniline-pyrimidines via sonogashira/suzuki cross coupling reactions catalyzed by novel CLPN-Pd. ChemistrySelect. 2021; 6 :13551-13558 - 6.
Tidwell TT. Hugo (Ugo) Schiff, Schiff bases, and a century of β-lactam synthesis. Angewandte Chemie International Edition. 2008; 47 :1016-1020 - 7.
Qin W, Long S, Panunzio M, Biondi S. Schiff bases: A short survey on an evergreen chemistry tool. Molecules. 2013; 18 :12264-12289 - 8.
Jos S, Suja NR. Synthesis, characterization, and study of catalytic activity of chiral Cu(II) and Ni(II) salen complexes in the α-amino acid C-α alkylation reaction. Inorganica Chimica Acta. 2023; 547 :121323 - 9.
Şener N, Özkinali S, Altunoglu YC, Yerlikaya S, Gökçe H, Zurnaci M, et al. Antiproliferative properties and structural analysis of newly synthesized Schiff bases bearing pyrazole derivatives and molecular docking studies. Journal of Molecular Structure. 2021; 1241 :130520 - 10.
Wanwu D, Khan SU, Khan QU, Khan S, Alam A, Ullah A, et al. In-situ phase transformation and microstructure of reinforced aluminium matrix composites (aa-6061 t6+nicr np) with and without tic nanoparticles. European Journal of Materials Science and Engineering. 2022; 7 :28-36 - 11.
Shi L, Ge H-M, Tan S-H, Li H-Q , Song Y-C, Zhu H-L, et al. Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde. European Journal of Medicinal Chemistry. 2007; 42 :558-564 - 12.
Siddiqui HL, Iqbal A, Ahmad S, Weaver GW. Synthesis and spectroscopic studies of new Schiff bases. Molecules. 2006; 11 :206-211 - 13.
Murahashi S. Synthesis of phthalimidines from schiff bases and carbon monoxide. Journal of the American Chemical Society. 1955; 77 :6403-6404 - 14.
El-Sonbati A, Mahmoud W, Mohamed GG, Diab M, Morgan SM, Abbas S. Synthesis, characterization of Schiff base metal complexes and their biological investigation. Applied Organometallic Chemistry. 2019; 33 :e5048 - 15.
Farooq M, Shujah S, Tahir K, Nazir S, Khan AU, Almarhoon ZM, et al. Ultra efficient 4-Nitrophenol reduction, dye degradation and Cr(VI) adsorption in the presence of phytochemical synthesized Ag/ZnO nanocomposite: A view towards sustainable chemistry. Inorganic Chemistry Communications. 2022; 136 :109189 - 16.
Kaya I, Vilayetoglu A, Mart H. The synthesis and properties of oligosalicylaldehyde and its Schiff base oligomers. Polymer. 2001; 42 :4859-4865 - 17.
Alemi AA, Shaabani B. Synthesis and characterization of a schiff base of p-tert-butylcalix[4]arene and its complex with copper(II). Acta Chimica Slovenica. 2000; 47 :363-369 - 18.
Uddin N, Rashid F, Ali S, Tirmizi SA, Ahmad I, Zaib S, et al. Synthesis, characterization, and anticancer activity of Schiff bases. Journal of Biomolecular Structure and Dynamics. 2020; 38 :3246-3259 - 19.
Liu J-J, Guo F-H, Cui F-J, Zhu J-H, Liu X-Y, Ullah A, et al. A biomass-derived N-doped porous carbon catalyst for the aerobic dehydrogenation of nitrogen heterocycles. New Journal of Chemistry. 2022; 46 :1791-1799 - 20.
Justin Dhanaraj C, Nair MS. Synthesis, characterization, and antimicrobial studies of some Schiff-base metal (II) complexes. Journal of Coordination Chemistry. 2009; 62 :4018-4028 - 21.
Imran S, Taha M, Ismail NH, Khan KM, Naz F, Hussain M, et al. Synthesis of novel bisindolylmethane Schiff bases and their antibacterial activity. Molecules. 2014; 19 :11722-11740 - 22.
Saleh EAM, Khan AU, Tahir K, Almehmadi SJ, Al-Abdulkarim HA, Alqarni S, et al. Phytoassisted synthesis and characterization of palladium nanoparticles (PdNPs); with enhanced antibacterial, antioxidant and hemolytic activities. Photodiagnosis and Photodynamic Therapy. 2021; 36 :102542 - 23.
Jarrahpour A, Motamedifar M, Pakshir K, Hadi N, Zarei M. Synthesis of novel azo Schiff bases and their antibacterial and antifungal activities. Molecules. 2004; 9 :815-824 - 24.
Khan KM, Khan M, Ali M, Taha M, Rasheed S, Perveen S, et al. Synthesis of bis-Schiff bases of isatins and their antiglycation activity. Bioorganic & Medicinal Chemistry. 2009; 17 :7795-7801 - 25.
Elbakoush FE, Khan QU, Ullah M, Ullah A, Khan AU, Khan J, et al. Characterization and Thermal Degradation Study of Carbonization the Polyimide (PMDA/ODA)/Fe Composite Films. Transactions on Electrical and Electronic Materials. 2021; 22 :843-850 - 26.
Hassan AS, Morsy NM, Aboulthana WM, Ragab A. Exploring novel derivatives of isatin-based Schiff bases as multi-target agents: Design, synthesis, in vitro biological evaluation, and in silico ADMET analysis with molecular modeling simulations. RSC Advances. 2023; 13 :9281-9303 - 27.
Habeeb MF, Sheat AM. Studies on Synthesis, Characterization and Biological Activities of Novel Schiff Bases from amino acridone. Egyptian Journal of Chemistry. 2023; 66 :225-234 - 28.
Beč A, Cindrić M, Persoons L, Banjanac M, Radovanović V, Daelemans D, et al. Novel biologically active N-substituted benzimidazole derived Schiff bases: Design, synthesis, and biological evaluation. Molecules. 2023; 28 :3720 - 29.
Shahab N, Kong D, Ali M, Alam A, Ur Rehman N, Ullah S, et al. Novel polyhydroquinoline Schiff’s base derivatives: synthesis, characterization, in vitro α-glucosidase inhibitory, and molecular docking studies. Research on Chemical Intermediates. 2023; 49 :1-24 - 30.
Devi P, Singh K, Kubavat B. Synthesis, spectroscopic, quantum, thermal and kinetics, antibacterial and antifungal studies: Novel Schiff base 5-methyl-3-((5-bromosalicylidene) amino)- pyrazole and its transition metal complexes. Results in Chemistry. 2023; 5 :100813 - 31.
Majid SA, Mir JM, Bhat MA, Shalla AH, Pandey A, Hadda TB, et al. A pair of carbazate derivatives as novel Schiff base ligands: DFT and POM theory supported spectroscopic and biological evaluation. Journal of Biomolecular Structure and Dynamics. 2023; 41 :5499-5515 - 32.
Maruthesh H, Katagi M, Nandeshwarappa B. A convenient synthesis, characterization and biological evaluation of novel schiff base heterocycles as potential antimicrobial, antitubercular agents and their structural activity relationship. Current Chemistry Letters. 2023; 12 :759-768