A HETEROCYCLE-FUNCTIONALIZED CARBA[3]FERROCENOPHANE AND PROCESS TO PREPARE THEREOF

Abstract

The present invention discloses a novel process (100) for the preparation of heterocycle functionalized carba[3]ferrocenophanes, wherein the carba[3]ferrocenophane framework comprises all the three bridged carbon atoms C1, C2, and C3 are functionalized. The process (100) includes mixing a heterocycle precursor with a solid support contained in a suitable flask to form a homogeneous powdery mixture, adding a ferrocenyl precursor to the mixture and stirring to obtain a homogeneous mixing, heating the mixture at a temperature in the range of about 40°C to 100°C under stirring, cooling the mixture at room temperature, extracting the resulting cooled product using an organic solvent to obtain a mixture of products, isolating and purifying of an individual product using chromatographic techniques and drying and storing the purified products.

Specification

Description:FIELD OF THE INVENTION
[0001] The present invention relates to a facile method for synthesizing all-carbon heterocycle-functionalized [3]ferrocenophanes using a unique solid-supported ring-closing approach. More specifically, the present invention is related to the solid-supported synthesis and characterization of all-bridging carbon functionalized [3] ferrocenophanes that incorporate various heterocyclic frameworks. The disclosure also discloses diastereomeric heterocycle tethered carba[3]ferrocenophanes for different heterocycles.
Therefore, the invention discloses a method to synthesize different heterocycle tethered, diastereomeric C1, C2, C3-functionalized carba[3]ferrocenophanes with stereo genic centers, using a solid state ring closing reaction approach.
BACKGROUND OF THE INVENTION
[0002] [n]Ferrocenophanes, characterized by their diverse bridging units and lengths, have garnered significant attention as a unique class of molecular entities over the past two to three decades.
[0003] Extensive research has been directed toward their synthesis and reactivity, particularly focusing on their unique structural and functional features. Both hetero-atom bridged and all-carbon-bridged ferrocenophanes, which can consist of saturated or unsaturated bridging components, have demonstrated remarkable potential in various applications, including their role as monomers in ring-opening polymerization.
[0004] The functionalization of bridging atoms in these ferrocenophanes opens up numerous opportunities to create compounds with varied functional characteristics. The distinct features of each functionalized ferrocenophane molecule depend on factors such as functionality, the number of bridging atoms, and ring strain.
[0005] Among these, all-carbon bridged [3]ferrocenophanes, which involve three bridging carbon centers, are particularly notable due to their stability and structural flexibility. Despite their promising attributes, the prospects for functionalization at the bridging carbon atoms have only been partially explored, highlighting the need for further investigation into their potential applications and functional diversity.
[0006] This background sets the stage for developing new synthetic methods that enhance the functionalization possibilities of all-carbon bridged [3]ferrocenophanes.
[0007] A literature survey indicates that carbon-bridged [3]ferrocenophanes have been extensively studied for mono- and di-functionalization at their bridging carbon centers. However, tri-functionalization at the C1, C2, and C3 bridging carbon atoms has largely remained unexplored, with limited information available regarding their synthesis, structural characteristics, and functional behavior.
[0008] Furthermore, there is currently no known research on heterocycle functionalization at these bridging carbon atoms in [3]ferrocenophanes. The lack of C1, C2 and C3-functionalized [3]ferrocenophanes is likely attributed to the challenging steric and electronic factors involved, as well as the absence of a straightforward synthetic strategy for achieving functionalization at all three carbon atoms.
[0009] Various prior art has tried to develop Oligomethylenferrocene. Monomere (\u201eansa-ferrocene\u201c), dimere und h\u00f6here polymere. For example, in a first literature, [Von Arthur Lüttringhaus, Werner Kullick, " Oligomethylenferrocene. Monomere („ansa-ferrocene"), dimere und höhere polymere" 1961, Volume 44, Issue 1 p. 669-681, https://doi.org/10.1002/macp.1961.020440150 the researchers disclose the sodium compounds of α,ω-dicyclopentadienyl alkanes with 3, 4, and 5 methyl groups were treated with FeCl3 or FeCl2 yielding oligomethylene ferrocenes. Thereby, monomeric ring systems were produced (Ansa-Ferrocenes"), a dimeric cyclic system, but mainly higher polymeric oligomethylene ferrocenes, which could be freed from the mixed hydrocarbons by means of the ferrocenium salts. The steric, and in particular, confirmative states were investigated and discussed.
[0010] In a second literature, [Viera Kaliská, Marta Sališová, Eva Solčániová and Štefan Toma, "Study of the reactivity of 2-(3-chlorobenzylidene)[3]ferrocenophane-1,3-dione" 1987, 52, 166-173, https://doi.org/10.1135/cccc19870166 ], the researcher disclosed the study of the reactivity of 2-(3-chlorobenzylidene)-[3]ferrocenophane-1,3-dione in Michael additions with various C-nucleophiles and cycloaddition reactions. It compares this reactivity with the analogous compound, 2-benzylidene-1,3-indanedione. The results reveal that the reactions lead to products like lactones and carbocyclic derivatives with expanded bridges. The reactivity differences between the ferrocenophane and benzene analogs, particularly in nucleophilic additions and bridge openings, are highlighted, with supporting evidence from NMR and IR spectroscopy.
[0011] However, still in the state of the art, there are persistent challenges and constraints in the state of the art. While carbon-bridged [3]ferrocenophanes have been well-studied for mono- and di-functionalization, tri-functionalization at the C1, C2, and C3 bridging carbon atoms remains unexplored due to steric and electronic difficulties, along with the lack of a straightforward synthetic approach. Similarly, highlights challenges in the reactivity of 2-(3-chlorobenzylidene)-[3]ferrocenophane-1,3-dione, where specific reactions result in complex product mixtures, and some nucleophilic additions fail due to steric hindrance or auto-condensation in basic conditions. These obstacles limit the full exploration of functionalized ferrocenophanes for advanced applications.
[0012] The present invention introduces innovative features by addressing key challenges in the synthesis and functionalization of [3]ferrocenophanes. Using a solid-supported approach, it simplifies the purification process, improves yield, and promotes environmental sustainability through the use of site materials like red mud.
[0013] Additionally, the invention enables the selective generation of chiral centers within ferrocenophanes, enhancing their structural diversity and expanding potential applications in areas such as asymmetric catalysis, chemical sensing, and environmental monitoring. The inclusion of heterocyclic functionalities further broadens their chemical diversity and functionality.
[0014] The potential advantages of creating fully functionalized ferrocenophanes are substantial, particularly because they could introduce chirality within the molecular framework. This chirality makes such compounds exceptionally valuable for applications in asymmetric catalysis and related fields. Achieving functionalization at all the bridging carbon atoms in [3]ferrocenophanes could result in the formation of two to three stereogenic centers, leading to asymmetric carba-ferrocenophanes with four to eight enantiomeric molecular frameworks. This diversity opens up opportunities to explore the biological, catalytic, and sensor applications of each of these enantiomeric and diastereomeric [3]ferrocenophanes.
[0015] Additionally, the specific properties of functionalized ferrocenophanes can vary based on the nature of the attached functionalities. For example, introducing donor functionalities to the bridging atoms may enhance the potential of these ferrocenophanes as receptors for molecular recognition studies. To expand the [3]ferrocenophane library by achieving complete functionalization of all bridging carbons with heterocyclic rings, this invention employs a unique solid-supported reaction approach. The invention discloses a method for synthesizing various heterocycle-tethered, C1, C2, C3-functionalized carba[3]ferrocenophanes with stereo genic centers, along with the extraction, purification, and characterization of these functionalized diastereomeric compounds using spectroscopic techniques and single-crystal X-ray diffraction.
OBJECTIVE OF THE INVENTION
[0016] The main objective of the present invention is to provide a simple and advantageous method for synthesis of C1, C2, C3- heterocycle functionalized carba[3]ferrocenophanes.
[0017] Another objective of the present invention is to provide a method involving facile and simple solid state reaction condition for synthesis of heterocycle tethered carba[3]ferrocenophanes.
[0018] Yet another object of the present invention is to establish an effective use of solid support including an industrial site with required composition, pH etc. for the solid supported synthesis of functionalized carba[3]ferrocenophanes.
[0019] Yet another object of the present invention is to generate stereo genic centers at the ferrocenophane bridge and isolate the diastereomeric ferrocenophanes.
SUMMARY OF THE INVENTION
[0020] In an aspect of the present invention, a simple and efficient method for synthesizing C1, C2, C3-heterocycle functionalized carba[3]ferrocenophanes, where all three bridged carbon atoms are functionalized is disclosed.
[0021] In the embodiment of the present invention, red mud powder and alumina powder are used as solid support to create an environment for the synthesis of heterocycle tethered diastereomeric C1, C2, C3 - functionalized carba[3]ferrocenophanes.
[0022] In one embodiment of the present invention, the synthesis process involves adding a heterocycle precursor to a solid support, mixing it with a ferrocenyl precursor, and heating the mixture to promote the formation of the desired products. After cooling, organic solvents are used for extraction, followed by chromatographic purification.
[0023] In one embodiment of the present invention, characterization of the synthesized products is performed using infrared spectroscopy, nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction studies. These techniques confirm the molecular structure and spatial orientation of the compounds, providing valuable insights into their chemical properties and applications.
[0024] In one embodiment of the present invention, the process for preparing heterocycle functionalized [3]ferrocenophanes involves adding a heterocycle precursor to a solid support in a flask to form a homogeneous mixture. This is combined with a ferrocenyl precursor and stirred, then heated to 40ºC-100ºC before cooling to room temperature. After cooling, organic solvents extract the products, which are isolated and purified by chromatography, and then dried and stored in vials.
[0025] This together with the other aspects of the present invention along with the various features of novelty that characterize the present disclosure is pointed out with particularity.
[0026] For a better understanding of the present disclosure, its operating advantages, and the specified objective attained by its uses, reference should be made to the accompanying descriptive matter in which there are illustrated exemplary embodiments of the present invention.
DESCRIPTION OF THE DRAWINGS
[0027] The advantages and features of the present invention will become better understood with reference to the following detailed description taken in conjunction with the accompanying drawings, in which:
[0028] Fig. 1A is a flow chart showing the process of preparing an heterocycle functionalized carba[3]ferrocenophanes, according to various embodiments of the present invention;

[0029] Fig. 1 illustrates a chemical reaction of a diastereomeric compound of [3]ferrocenophanes, according to various embodiments of the present invention;

[0030] Fig. 2 illustrates chemical reaction of one pot reaction approach, according to various embodiments of the present invention;

[0031] Fig. 3 illustrates a 1H NMR of compound 5a and 5b (CDCl3, 400 MHz), according to various embodiments of the present invention;

[0032] Fig. 4 illustrates a 1H NMR of compound 6a and 6b (CDCl3, 400 MHz), according to various embodiments of the present invention;

[0033] Fig. 5 illustrates a molecular structure of stereoisomeric ferrocenophanes (5a) in the crystal, according to various embodiments of the present invention;

[0034] Fig. 6 illustrates a molecular structure of diastereomeric derivatives (6a & 6b) in the crystal, according to various embodiments of the present invention;

[0035] Fig. 6A illustrates a graphical representation of a DPV of 6a on gradual addition of Picric acid (PA) in (a) solution, (b) vapor phase, according to various embodiments of the present invention;

[0036] Fig. 7 illustrates a graphical representation of a chiral HPLC of 6 showing 1R,3R and 1S,3S enantiomers, according to various embodiments of the present invention;

[0037] Fig. 7A illustrates a graphical representation of a cyclic voltammetry and Differential pulse voltammetry of 5 - 6, according to various embodiments of the present invention;

[0038] Fig. 7B illustrates a graphical representation of a (a) Device for PA sensing; (b) I-V Plot of 6a on gradual addition of PA, according to various embodiments of the present invention;

[0039] Fig. 8 illustrates a graphical representation of a selective detection of 6a using dpv, according to various embodiments of the present invention;

[0040] Fig. 9 illustrates a graphical representation of a Shift in the 1H NMR (400 MHz, CDCl3) upon interaction of 6 with Picric acid, according to various embodiments of the present invention; and

[0041] Fig. 10 illustrates an optimized structure of [6.PA], according to various embodiments of the present invention.

[0042] Like numerals denote like elements throughout the figures.

DESCRIPTION OF THE INVENTION

[0043] The exemplary embodiments described herein detail for illustrative purposes are subjected to many variations. It should be emphasized, however, that the present invention is not limited to as disclosed.

[0044] It is understood that various omissions and substitutions of equivalents are contemplated as circumstances may suggest or render expedient, but these are intended to cover the application or implementation without departing from the spirit or scope of the present invention.

[0045] Specifically, the following terms have the meanings indicated below.

[0046] The terms "a" and "an" herein do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced items.

[0047] The terms "having", "comprising", "including", and variations thereof signify the presence of a component.

[0048] More specifically, the technical terms used herein are to be understood as commonly known by those skilled in the field.

[0049] The inventive aspects of the invention along with various components and engineering involved will now be explained with reference to figures 1-10 herein.

[0050] In an aspect of the present invention, a process (100) for the preparation of heterocycle functionalized carba[3]ferrocenophanes, wherein the carba[3]ferrocenophane framework comprises all the three bridged carbon atoms C1, C2, and C3 are functionalized is disclosed.

[0051] Referring to Fig. 1A, a flowchart is shown representing steps of preparing heterocycle functionalized carba[3]ferrocenophanes, wherein the carba[3]ferrocenophane framework comprises all the three bridged carbon atoms C1, C2, and C3 are functionalized.

[0052] The process, as illustrated in Fig. 1A, begins with step 10, where a heterocycle precursor is combined with a solid support within a suitable flask. This initial step aims to create a homogeneous powdery mixture, setting the foundation for subsequent reactions. Following this, step 12 involves the addition of a ferrocenyl precursor to the prepared mixture. The mixture is then stirred thoroughly to ensure a uniform distribution and blending of the components.

[0053] As the process advances to step 14, the mixture undergoes heating at a controlled temperature, typically ranging from 40°C to 100°C. Continuous stirring is maintained throughout this phase to facilitate an even reaction. After the heating process, step 16 involves cooling the mixture down to room temperature, preparing it for the next extraction phase.

[0054] At step 18, an organic solvent is employed to extract the cooled product, yielding a mixture that contains the desired compounds. The process continues with step 20, where chromatographic techniques are used to isolate and purify the specific product from this mixture, ensuring that the final output is of high purity and quality. Finally, in step 22, the purified products are carefully dried and stored, completing the process. Each step is critical to achieving the intended results, and precise control of conditions ensures the success of the entire procedure.

[0055] In another embodiment of the invention, the solid support used in the process comprises a combination of red mud and alumina, which can be mixed in varying proportions to achieve the desired reaction conditions. The heterocycle precursor employed in this embodiment consists of a bis-functionalized heterocyclic unit, which features a pendant carboxaldehyde or a heterocycle-enone chain, providing versatility in the types of products that can be synthesized.

[0056] Additionally, the process makes use of ferrocenyl precursors, specifically selecting substrates that contain ferrocenyl moieties. Examples of such substrates include compounds like 1,1'-ferrocenedicarboxaldehyde or acetyl-substituted heterocycles. During the reaction, the temperature is carefully controlled within the range of about 40°C to 100°C. Under these conditions, a yellow compound is formed, proceeding through a violet intermediate stage, indicating the progress of the chemical transformation.

[0057] The resulting products from this reaction are characterized using advanced spectroscopic techniques, including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). These analyses confirm the identity and structure of the products. Specifically, the process yields diastereomeric carba[3]ferrocenophanes, where the C1, C2, and C3 carbon atoms are functionalized with heterocyclic groups. These functionalizations are achieved using solid-supported reaction conditions, demonstrating the efficiency and utility of the solid support medium.

[0058] The diastereomeric carba[3]ferrocenophanes produced in this process are further verified through single-crystal X-ray diffraction, which provides precise structural confirmation. In yet another embodiment of this invention, a distinct class of diastereomeric compounds of [3]ferrocenophanes is disclosed. These compounds feature at least three stereogenic centers located at the C1, C2, and C3 carbon atoms, formed through a solid-state ring-closing reaction. The C1 and C3 atoms are functionalized with heterocyclic groups, and the configuration exhibits chiral arrangements, resulting in enantiomers.

[0059] Furthermore, the stereogenic C2 carbon atom is designed to have a meso-type stereoisomer configuration, which is determined by the specific functional groups attached to the C1, C2, and C3 positions. The detailed molecular structure of these compounds is confirmed using single-crystal X-ray diffraction, ensuring accurate identification and validation of the stereochemistry and functional arrangements within the molecule.

[0060] In an aspect of the present invention, referring to Fig.1 a solid supported reaction of substrate 4a-d, with acetyl heterocycle (2a-d) gave selectively a yellow compound, 6a-d, in high yield is disclosed. Referring to Fig. 2, illustrates the one pot reaction approach. In both these stepwise reaction, selective products are obtained.

[0061] The compounds 5a-d and 6a-d are also obtained during a one-pot reaction approach using 1,1'-ferrocenedicarboxaldehyde with excess of acetyl heterocycle under the solid supported condition when the reaction is continued for extended hours at temperature ranging from 40º-100º C. In this one-pot reaction condition, all the three compounds are obtained in different yields, depending upon the time of reaction.

[0062] A range of different solid support has been used like red mud (industrial iste), basic alumina, neutral alumina, combination of alumina and red mud in different proportions.

[0063] The table below illustrates the Comparison of One-Pot Reactions for Heterocycle Synthesis Using Different Solid Supports

Solid support
Heterocycles Redmud support
[Temp, time (yields)] Basic alumina support
[Temp, time (yields)] Neutral alumina support.
[Temp, time (yields)] 50% redmud/ alumina support.
[Temp, time (yields)]
Pyridine 70º, 30-40 h (5a=30%,6a=46%) 70º, 6-10 h (5a=42%,6a=48%) 70º, 6-10 h
(5a=44%,6a=48%) 70º, 12-15h
(5a=44%,6a=50%)
thiophene 70º, 20-25 h (5b=32%,6b=45%) 70º, 6-8 h
(5b=45%,6b=50%) 70º, 6-8 h
(5b=45%,6b=50%) 70º, 8-10h
(5b=44%,6b=50%)
furan 70º, 12-20 h
(5c=30%,6c=45%) 70º, 6-8 h
(5c=40%,6c=50%) 70º, 6-8 h
(5c=40%,6c=50%) 70º, 10-12h
(5c=40%,6c=48%)
pyrrole 70º, 20-30 h (5c=28%,6c=33%) 70º, 10-12 h
(5d=33%,6d=40%) 70º, 10-12 h
(5d=33%,6d=40%) 70º, 15-20h
(5d=30%,6d=44%)
Table 1: Comparison of reaction condition for different Heterocycle and Solid Supports

[0064] Referring to Fig. 3 and Fig.4, it shows compounds 5a-d & 6a-d are extracted in dichloromethane, purified by short column chromatography and characterized using infrared, 1H, 13C NMR, and ESI-HRMS spectroscopic techniques, while the unusual structural identity of 5a and 6a is revealed using single crystal X-ray crystallography.

[0065] Referring to Fig. 5 and Fig.6, the structural identities of compounds 5a and 6a are confirmed using single crystal X-ray diffraction, with crystals grown from an n-hexane/dichloromethane solvent mixture at -10ºC is shown. Both compounds have a [3]ferrocenophane framework, where all three bridging carbon atoms (C1-C3) are functionalized. C1 and C3 are linked to -CH2CO(C5H4N) groups, while C2 is bonded to -CO(C5H4N).

[0066] Although 5a and 6a share similar functionalization, they differ in their conformations, making them stereoisomers. In 5a, C1 and C3 substituents are on the same side, and C2 is trans to both, generating a plane of symmetry through C2. In contrast, in 6a, the C2 substituent is cis to C1 and trans to C3, creating two chiral centers at C1 and C3. For both molecules, the C=O group is oriented opposite to the pyridyl nitrogen.

[0067] Referring to Fig.7, it represents the Spectroscopic and structural analysis identified compound Q as 1-(1,3-bis picolinoyl-2-propyl)-1'-(vinylpicolinoyl) ferrocene. Compounds 5a-d and 6a-d are diastereomeric derivatives, with two or three chiral centers at the bridging carbons.

[0068] The C1 and C3 functional groups are oriented in the same direction, forming a meso-type derivative. In contrast, 6a-d is a racemic mixture of enantiomers with opposite orientations of the functional chains at C1 and C3, creating a chiral arrangement. Chiral HPLC analysis of 6a-d shows two distinct bands for the 1S, 3S and 1R, 3R enantiomers, confirming chirality at C1 and C3.

[0069] Referring to Fig. 8, it represents an electrochemical study of compounds 5 and 6 are conducted in acetonitrile using cyclic voltammetry (CV) and differential pulse voltammetry (DPV).

[0070] The compound 6a, with non-conjugated pyridyl chains on the Cp rings, exhibited a single reversible Fe(II)/Fe(III) redox process at +0.50 V. In contrast, compound Q, featuring a conjugated vinylpicolinoyl chain, showed a higher potential redox couple at +0.675 V. The diastereomer 5a displayed a similar reversible Fe(II)/Fe(III) redox process at +0.485 V.

Compounds Epa(V) Epc(V) E1/2 (V)
(E (mV)) dpv (V)
Qa +0.73 +0.62 +0.675, (110) +0.72
5a +0.53 +0.44 +0.485, (90) +0.53
6a +0.55 +0.45 +0.50, (100) +0.55
Table - 2

[0071] Table 2 refers to a cyclic voltammetry and differential pulse voltammetry data of 5 - 6.

[0072] Referring to Fig. 8 and Fig. 9, it represents an electrochemical probe diagram showcasing the potential of 6a for picric acid detection. The electrochemical sensing potential of compound 6a, a pyridyl-functionalized ferrocenophane, for detecting picric acid (PA), a nitroaromatic compound used in explosives and known for its environmental toxicity. The unique structure of 6a, with three pyridyl groups oriented in different directions, is hypothesized to interact with PA, leading to conformational and electronic changes in the ferrocenyl system, which could enhance its electrochemical behavior for sensor applications.

[0073] The compound 6 exhibits a reversible oxidative couple at +0.55 V, attributed to the ferrocene/ferrocenium couple.

[0074] However, when tested with various nitroaromatic compounds, including 2,4-dinitrophenol (DNP), 2,4-dinitrotoluene (DNT), 4-nitrophenol (NP), and 4-nitrotoluene (NT), no significant shifts are observed during the sensing experiments. This suggests that the interactions between compound 6a and these nitroaromatic compounds do not lead to detectable changes in electrochemical behavior.

[0075] Referring to Fig. 9 and Fig. 10, it represents an NMR spectral changes, highlighting the shifts of protons, and molecular structure of the complex formed between compound 6 and picric acid, showing hydrogen bonding interactions. F13 details the molecular interaction between compound 6a and picric acid (PA), studied through ^1H NMR titration in CDCl₃ solution.

[0076] The hydroxyl proton of PA at δ 11.74 disappeared upon interaction, while the aromatic protons shifted from δ 9.22 to δ 9.19 with one equivalent of PA, and to δ 9.16 with two equivalents, indicating complex formation. Shifts are also noted for the aromatic protons of the pyridyl moiety, suggesting strong hydrogen bonding interactions.

[0077] A broad peak at δ 5.02 emerged with the addition of PA, shifting to δ 5.27 with further addition. Geometry optimization and DFT calculations indicated that two PA molecules interact directly with two pyridyl nitrogen atoms, while one remains free.

EXAMPLE:
Example-1: One pot synthesis of 5 and 6
Materials:
[(5-C5H4-CHO)2Fe], have been prepared according to the literature method and 2-acetyl pyridine, 2-acetyl thiophene, 2-acetyl furan, 2-acetyl pyrrole is used as purchased.
Apparatus:
All the experiments carried out under a solvent free solid supported reaction condition using round bottomed flask or beaker. Infrared spectra are recorded on a Perkin Elmer Spectrum 2 spectrometer as CH2Cl2 solution and NMR spectra on a 400 MHz Bruker spectrometer in CDCl3 solvent. Elemental analyses are performed on a Vario El Cube analyser. ESI-HRMS spectra are obtained on a Waters XEVO G2-XS QTOF MS instrument operating in ESI mode. Cyclic voltammetric and differential pulse voltammetric measurements are performed with a CH Instruments model 600D electrochemistry system. A platinum working electrode, a platinum wire auxiliary electrode and an Ag/AgCl reference electrode are used in a three-electrode configuration. The supporting electrolyte is 0.1 M [NBu4]ClO4 and the solute concentration is 103 M. The scan rate used is 50 mV s1.
Preparation of 5 and 6
1,1'-Ferrocenedicarboxaldehyde (1.0 mmol, 242 mg) and 2-acetyl pyridine (3.0 mmol, 0.3 ml) or other heterocycle precursor is taken in a 100 mL round bottomed flask and the reaction mixture is thoroughly mixed with 5 grams of finely ground redmud powder or other solid support in the round bottomed flask. The mixture is heated using an water bath to 70ºC under stirring condition using a magnetic stirrer and continued for 40 hours (different time interval for different solid support). The reaction mixture is then extracted in dichloromethane solvent, dried under vacuum and subjected to column chromatography with hexane/ethyl acetate (70:30 v/v) solvent mixture to obtain 5 and 6 as per elution. Some decomposition has also been observed after the reaction.

Example-2: Stepwise synthesis of 5
(3a-d) (0.5 mmol) and 2-acetyl heterocyclic precursor (0.5 mmol) is taken in a 100 mL round bottomed flask and thoroughly mixed with finely ground redmud powder (5 g) or other solid support in the round bottomed flask and heated at 70ºC using water bath under continuous stirring using a magnetic stirrer. On extraction of the mixture, after 20 hours of the reaction, using dichloromethane and subsequent chromatographic work up using short column chromatography a yellow coloured compound, 5 is isolated using column chromatography with hexane/ethyl acetate (70:30 v/v) solvent mixture as eluent. Some amount of other compound, Q is also isolated.

Example-3: Stepwise synthesis of 6
Ferrocenyl dipyridyl chalcone (4) (1.0 mmol) and 2-acetyl heterocyclic precursor (1.0 mmol) are taken in a 100 mL round bottomed flask and 5 grams of redmud powder or other solid support is added to it and continuously stirred for 10 minutes for homogenous mixing and heated at 70ºC using water bath under continuous stirring using a magnetic stirrer continued for 15 hours. After completion of the reaction, the mixture is extracted in dichloromethane, dried under vacuum and subjected to short column chromatography. Elution with ethyl acetate/hexane (30:70 v/v) solvent mixture afforded a yellow colored compound 6.

Advantageous effects of the present invention

[0078] In one embodiment of the present invention, using solid support to synthesize heterocycle functionalized ferrocenophanes provides significant advantages, especially in simplifying purification processes. This approach allows researchers to more easily isolate the desired products from the reaction mixture, reducing the complexity of synthesis, saving time, and minimizing the need for excessive solvents.

[0079] In one embodiment of the present invention, the solid-supported synthesis enhances efficiency, resulting in higher yields of target ferrocenophanes. This increase in productivity is particularly advantageous for applications requiring larger quantities of these functionalized compounds, thereby improving their commercial viability.

[0080] In one embodiment of the present invention, the use of solid support enhances environmental sustainability by incorporating is the materials like red mud into the synthesis process. This approach reduces environmental impact, promotes recycling of industrial byproducts, and aligns with green chemistry principles, making the synthesis eco-friendlier and appealing to researchers and industries focused on sustainability.

[0081] Lastly, the method facilitates the selective generation of chiral centers in ferrocenophanes, crucial for controlling stereochemistry. This capability enhances structural diversity by producing meso-type trans-isomers and enantiomers, leading to novel chemical properties.

[0082] The incorporation of heterocyclic functionalities further expands this diversity, as seen in compounds with multiple pyridyl units that effectively sense picric acid (PA) at ppb levels, highlighting their potential applications in chemical sensing and environmental monitoring.

[0083] In a nutshell, the method and the composition of the present invention overcome the drawbacks discussed in the conventional techniques and provided a cost effective and efficient way of preparing heterocycle functionalized carba[3]ferrocenophanes.

[0084] The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of description. They are not intended to be exhaustive or to limit the present invention to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching.

[0085] Further, the embodiments are chosen and described in order to best explain the principles of the present invention and its practical application, and thereby enable others skilled in the art to best utilize the present invention and various embodiments with various modifications as are suited to the particular use contemplated.

[0086] It is understood that various omissions and substitutions of equivalents are contemplated as circumstances may suggest or render expedient, but such omissions and substitutions are intended to cover the application or implementation without departing from the spirit or scope of the present invention.
, C , C , Claims:1. A process (100) for preparation of heterocycle functionalized carba[3]ferrocenophanes, wherein the process (100) comprises the steps of:

mixing a heterocycle precursor with a solid support contained in a suitable flask to form a homogeneous powdery mixture;
adding a ferrocenyl precursor to the mixture and stirring to obtain a homogeneous mixing;
heating the obtained homogeneous mixture;
cooling the mixture at room temperature;
extracting the resulting cooled product using an organic solvent to obtain a mixture of products;
isolating and purifying of an individual product using chromatographic techniques; and
drying and storing the resulting compound,
wherein the carba[3]ferrocenophane framework comprises all the three bridged carbon atoms C1, C2, and C3 which are functionalized,

2. The process (100) as claimed in claim 1, wherein the solid support comprises a combination of red mud and alumina in different proportions.

3. The process (100) as claimed in claim 1, wherein the obtained homogeneous mixture is heated at a temperature in the range of about 40°C to 100°C under stirring.

4. The process (100) as claimed in claim 1, wherein the heterocycle precursor comprises a bis-functionalized heterocyclic unit and a pendant carboxaldehyde or a heterocycle-enone chain.

5. The process (100) as claimed in claim 1, wherein the ferrocenyl precursor comprises a ferrocenyl substrates.

6. The process (100) as claimed in claim 4, wherein the ferrocenyl substrates are selected from ferrocenyl moiety with groups comprising 1,1'-ferrocenedicarboxaldehyde or acetyl heterocycles.

7. The process (100) as claimed in claim 1, wherein the heating temperature is about 40ºC to 100ºC to form a yellow compound via formation of a violet intermediate.

8. The process (100) as claimed in claim 1, wherein the products are characterized using infrared (IR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) spectroscopic analysis.

9. The process (100) as claimed in claim 1, wherein the product is diastereomeric carba[3]ferrocenophane with C1, C2, and C3 carbon atoms functionalized with the heterocyclic groups.

10. The process (100) as claimed in claim 8, wherein the C1, C2, and C3 carbon atoms functionalized [3]ferrocenophane is obtained using solid-supported reaction condition.

11. The process (100) as claimed in claim 8, wherein the diastereomeric carba[3]ferrocenophanes produced are confirmed using single-crystal X-ray diffraction technique.

12. A diastereomeric compound of [3]ferrocenophanes, wherein the compound comprises at least two stereogenic centers at C1, C2, and C3 carbon atoms derived via a solid-state ring closing reaction, and functionalized with heterocycle groups at C1 and C3, wherein the diastereomeric compound is characterized by chiral arrangement with enantiomers.

13. The compound as claimed in claim 12, wherein the heterocyclic moieties comprises of pyridyl, thiophene, furan, or pyrrole functional groups.

14. The compound as claimed in claim 12, wherein the stereogenic C2 carbon is configured to meso type stereoisomer depending on the functional groups attached to the C1, C2, and C3 atoms.

15. The compound as claimed in claim 12, wherein the molecular structure of the compound is confirmed using single crystal X-ray diffraction.

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