Cobalt (II) complexes bearing n,n-bidentate ligand: preparation process and synthetic applications

Abstract

The present invention relates to a process of preparation of bench-stable Co(II)- complexes of formula I, encompassing phosphine-free N,N-bidentate ligand system and its catalytic use for the purpose of studying the N-alkylation of hetero-aromatic amines with alcohol using the borrowing hydrogenation method. Further, the present invention uses the complex of formula I, which has also been directed to synthesizing substituted quinolines by coupling phenyl ethanol and 2-aminobenzyl alcohols together via a modified Friedlander reaction. Furthermore, the easily synthesized N,N-bidentate ligand demonstrated that benchmark tridentate pincer ligands might potentially be replaced, marking a novel development in the homogeneous catalytic reaction of hetero-aromatic amines.

Description

[0001] COBALT (II) COMPLEXES BEARING N,N-BIDENTATE LIGAND: PREPARATION PROCESS AND SYNTHETIC APPLICATIONS CROSS REFERENCE TO THE RELATED APPLICATION: This application claims the benefit of the earlier filing date of Indian Patent Application No.202441043507 filed on June 05, 2024; the entire contents of each of which are incorporated by reference herein. FIELD OF THE INVENTION: The present invention relates to a process for the preparation of Cobalt(II)-N,N- bidentate complex synthesized by reacting cobalt bromide precursors with pyridine- based N,N-bidentate ligands. This complex is used catalytically for the N-alkylation of hetero-aromatic amines with alcohol. Additionally, the present invention further relates to the Cobalt(II)-N,N-bidentate complex as an efficient catalyst for producing diverse mono-alkylated amines in excellent yields via hydrogen borrowing strategy, generating water as the sole by-product. BACKGROUND OF THE INVENTION: Nitrogen-containing molecules such as amines and their derivatives are highly valuable compounds for chemical and life science applications. Particularly, the selective mono-alkylated (hetero)-aromatic amine-derived molecules have widespread applications in pharmaceuticals, agrochemicals, lubricants, organic dyes, corrosion inhibitors, surfactants, potential ligands in homogeneous catalysis, and material chemistry. Because of their importance and practicality in many fields of chemistry, a series of synthetic methodologies has been established to produce amine products. Conventionally, N-alkylated amine derivatives were synthesized by reacting the primary amines with alkyl halides in the presence of base or by reductive amination pathway. However, over-alkylation, low yield, relatively harsh reaction conditions, and the generation of toxic waste limit their applicability. Therefore, N- alkylation reactions with good selectivity, high yield, and better atom economy with mild reaction conditions are highly demanding in the synthetic community as a sustainable synthetic protocol. Due to the green features and readily available alcohols, the transition metal- catalyzed N-alkylation reaction of amine using alcohol as an alkylating agent, namely the Borrowing Hydrogen (BH) or Hydrogen Auto-transfer (HA) methodology, is recognized as an alternative atom-economic synthetic strategy for expedient production of N-alkylated amines with water as the only by-product. In this regard, numerous reports based on precious metal (Ru, Ir, Rh, and Pd) catalyzed N-alkylation amines or amination of alcohol via BH / HA strategy have been well-documented. Alternatively, developing more sustainable, earth-abundant, and first-row metal (Fe, Co, Ni, Cu, and Mn) complexes are highly desired for alcohol-amine coupling reactions to synthesize N-alkylated amine derivatives in an environmentally benign pathway. However, heterocyclic amines as nucleophiles provide an additional challenge in catalytic borrowing hydrogen processes. Due to the poisoning effects, these nucleophiles are typically undesired for late-transition metal-catalyzed reactions. Indeed, Lindlar's catalyst is a palladium catalyst poisoned with traces of lead and quinoline, which is used to reduce alkynes to alkenes. For that, developing a new strategy for the selective mono-alkylation of (hetero)-arene amines with alcohols is more appealing and advantageous. In recent years, reports suggest that molecular cobalt complexes may operate as suitable catalysts for (de)hydrogenative N-alkylation and related reactions. To date, a handful of examples are known based on cobalt-catalyzed selective amine alkylation reactions and (BH) C-C and C-N bond-forming reactions. On the other hand, very few reports were related to the Co-based selective N-alkylation reaction of heteroarene amine utilizing sustainable alcohols. Interestingly, the majority of them only provided a few examples relevant to N- substituted (hetero)-aromatic amines (Scheme 1). A research article by Kempe et al., 2015, Angewandte Chemical International Edition, 54: 15046–15050, discloses a PN5P ligand with triazine backbone stabilized Co(II)-PNP pincer complex employed for the efficient N-alkylation of 3-aminopyridine with various alcohols (6 examples). Another publication by Kirchner et al., 2016, Organic Letters, 18(14): 3462–3465, discloses the development of a molecular cobalt (II) complex stabilized by an anionic PCP ligand based on the 1, 3-diaminobenzene scaffold for the N-alkylation of 3- aminopyridine (4 examples) and 2-aminopyrimidine (2 examples). In Midya et al., 2018, Catalysis Science & Technology, 8 (14): 3469-3473, the pioneers of the present invention demonstrated the use of NNN-Co(II) complex for the N-alkylation of 8-aminoquinoline and 2-aminopyridine (1-1 example) with benzyl alcohol. Another study by Ding et al., 2021, published in the Journal of Organometallics, 40(3): 418-426, discloses switchable imine and amine synthesis of 3- aminopyridine with benzyl alcohol catalyzed by a tripodal ligand-supported well-defined cobalt complex. In yet another study, Ramakrishnan et al., 2021, published in the journal of Chemistry Select, 6(33): 8766-8773, disclose a magnetically recyclable heterogeneous Cobalt Ferrite catalyst for the direct N-alkylation of 2-aminopyrimidine and 2- aminopyridine (1-1 example) with benzyl alcohol along with quinoline synthesis via acceptorless dehydrogenative coupling (ADC) (11 examples). However, there is no example known for the Co-catalyzed borrowing hydrogen reactions of 6-aminoquinoline with alcohols in the prior arts. The prior examples of molecular cobalt (II) complexes employed for the N-alkylation reactions are mainly based on tridentate ligands and applicable only to simple aromatic and aliphatic amines, as presented in Scheme 1. e of the art Therefore, there is a need for an alternative process for the efficient alkylation of (hetero)-aromatic amines by alcohols catalyzed by a bench-stable, phosphine-free, versatile cobalt pre-catalyst stabilized by a cobalt (II) complexes bearing N, N- bidentate ligand to synthesize N-alkylated amine derivatives in an eco-friendly manner. OBJECTS OF THE INVENTION: The primary object of the present invention is to synthesize Cobalt (II) complexes bearing N,N-bidentate ligand by reacting cobalt bromide precursors with pyridine- based N, N-bidentate ligands. Another object of the present invention is to characterize the synthesized N,N- bidentate ligands, and Co(II) complexes by various analytical and spectroscopic methods. Yet another object of the invention is to evaluate the catalytic efficiency of Cobalt (II) complexes in the C-N coupling and annulation reactions involving alcohols via the borrowing hydrogen (BH) strategy. SUMMARY OF THE INVENTION: The present invention provides a process for the preparation of Cobalt (II)-N,N- bidentate complex of formula I, to synthesize N-alkylated amine derivatives in an eco-friendly manner. The present catalytic methodology can be applied to a wide range of substrates by varying alcohols, including aryl, aliphatic, acyclic, and cyclic groups, with hetero-aromatic amines such as aminopyridine, 2-aminopyrimidine, and aminoquinoline to provide diverse mono-alkylated organo-nitrogen compounds in good to excellent yields. Accordingly, the primary aspect of the present invention is to provide a process for the preparation of Cobalt (II)-N,N-bidentate complex of formula I, comprising the steps of: (i) reacting 2-(chloromethyl) pyridine hydrochloride of formula IV with morpholine of formula III in the in a solvent; (ii) cooling the reaction mixture and removing the solvent under vacuum, the resulting residue was extracted with a solvent and water mixture; (iii) drying the organic layer over a salt and evaporating the solvent to obtain the compound of formula II ; (iv) reacting the compound of formula II with anhydrous CoBr2 in the presence of a solvent; and (v) filtering the above solution to obtain the compound of formula I. In the said process of step (i), the experiment is conducted at temperatures ranging from 75-105 °C for a duration of 5-15 hours under the N2 atmosphere. In the said process, the compound of formula II is 4-(pyridine-2- ylmethyl)morpholine (N,NMor(L1)). Further, in step (i) of the above-mentioned process, the base is selected from a group comprising calcium hydroxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, trimethylamine, sodium tert-butoxide, potassium hydride, barium hydroxide, and the preferable base is potassium hydroxide. The solvent employed in step (i) is selected from a group comprising acetone, methanol, ethanol, ethyl acetate, acetonitrile, isopropanol, butanol, or mixtures thereof, and the preferable solvent is acetonitrile. In the said process of step (iii), the yield of the compound of formula II is 85%. The solvent employed in step (ii) is selected from a group comprising chloroform, dichloromethane, acetonitrile, diethyl ether, dimethyl formamide, dimethoxy ethane, dimethyl acetamide, dioxane and mixtures thereof and the preferable solvent is dichloromethane. In the said process, the salt used in step (iii) is selected from a group comprising sodium hydroxide, sodium chloride, sodium sulfate, sodium fluoride, sodium bromide, sodium iodide, and sodium bicarbonate. In the said process, the solvent used in step (iv) is selected from a group comprising methanol, ethanol, methyl acetate, heptane, hexane, and diethyl ether, and the preferable solvent is methanol. In the said process of step (v) the yield of the compound of formula I is 92%. Accordingly, in the present invention a (NN)MorCoBr2bidentate complex I of formula I is obtained by the said process. Accordingly, a process for preparing N-alkylated heterocyclic amines in the presence of a compound of formula I reacting heterocyclic amines with alcohols in the presence of a compound of formula I, a base, and a solvent. In the said process, the heterocyclic amines are selected from groups comprising aminopyrimidine, aminoquinoline, aminopyridine, or derivatives thereof. In the said process, the base is selected from a group comprising calcium carbonate, potassium hydroxide, cesium carbonate, potassium tert-butoxide, sodium tert- butoxide, potassium hydride, trimethylamine or mixtures thereof and the preferable base is potassium tert-butoxide. In the said process, the solvent is selected from a group comprising xylene, toluene, tetrahydrofuran, n-octane, ethyl acetate, butyl acetate, 1,4-dioxane, cyclohexane or mixtures thereof and the preferable solvent is toluene. BRIEF DESCRIPTION OF THE DRAWINGS: FIG.1: The absorption spectrum of complex (NN)MorCoBr2in ACN (1x104M) at 298 K. FIG.2:1H NMR spectrum of L1 (formula II) FIG.3:13C NMR spectrum of L1 (formula II) FIG.4: Mass spectrum of complex I (formula I) FIG. 5: Representation of the molecular structure of complex I (formula I) with 50% probability ellipsoids. Hydrogens are omitted for clarity. FIG.6:1H-NMR (400 MHz) spectra of isolated complex (4 mM) in CDCl3(0.1 % TMS). FIG.7: Gasometer analysis for the detection of hydrogen FIG.8:1H NMR of deuterated 4-methoxybenzyl alcohol FIG.9:1H NMR of deuterated N-((4-methoxyphenyl)methyl-d2)quinolin-6-amine. FIG. NMR of deuterated N-((4-methoxyphenyl)methyl-d2)pyridin-3-amine. DETAILED DESCRIPTION OF THE INVENTION: Accordingly, the primary aspect of the present invention discloses and describes a process for the synthesis of formula I, i.e., (N, N)Mor-CoBr2(I) (referred to as complex I hereafter). Complex I was synthesized by reacting the N,NMorbidentate ligand (L1) of formula II with anhydrous CoBr2 in acetonitrile at room temperature, resulting in the corresponding Co-complex in 92 % isolated yield as described in Scheme 2. Moreover, the steps involved in the synthesis of Complex I are further demonstrated in Example 1. Scheme 2. Synthesis of (NN)MorCoBr2 bidentate complex. Another aspect of the present invention is to provide the catalytic activity of the freshly prepared phosphine-free (N,N)MorCoBr2bi-dentate complex is used as a pre- catalyst for the selective hetero-aromatic amine alkylation process employing alcohols as alkylating agents. In one of the preferred embodiments, the complex employed in the screening step of catalytic reactions of phosphine-free (N,N)MorCoBr2 bi-dentate complex could be Complex I or Complex II. A preferred embodiment of the present invention is that the solvent employed in the screening step of catalytic reactions of phosphine-free (N,N)MorCoBr2 bi-dentate complex could be selected from the group comprising Toluene, THF, Neat, n-Octane. Another preferred embodiment of the said invention is that the base employed in the screening step of catalytic reactions of phosphine-free (N,N)MorCoBr2 bi-dentate complex could be selected from the group comprising KOtBu, (KOH, Cs2CO3, and Et3N). Further, preferred embodiments of the present invention are that the other parameters operated in the screening step of catalytic reactions of phosphine-free (N,N)MorCoBr2bi-dentate complex include time and temperature wherein time ranges from 10-20 hrs more preferably 12-18 hours, and most preferably 18 hours and temperature is maintained at 130 °C. The inventors of the present invention found that in order to initiate the C-N bond- forming reaction, 2-aminopyrimidine and benzyl alcohol were preferred as benchmark substrates, as referred to in Table 1. Using these substrates, a number of reaction parameters, such as solvents, reaction temperature, and base, were systematically investigated, which are described in Table 1 for optimization studies. The screening of catalytic conditions typical experiments with the reaction of 2- aminopyrimidine (1a) benzyl alcohol (1b) and a catalytic amount of (NN)MorCobalt complex (I; 1 mol%) and KOtBu (50 mol%) in toluene at 130 °C (silicon oil-bath temperature) refluxed for 12h, afforded the corresponding N-alkylated product benzylpyrimidin-2-amine (2) in 66% yield. Furthermore, a marginal change in the yield (58%) was observed with complex II at the same reaction condition (Table 1, entries 1 and 2) wherein the complex I and complex II are given as follows; and THF resulted in 62% and 41% yields, respectively, as solvents. Due to the extremely low solubility of starting materials, poor yield was observed in solvent-free conditions (Table 1, entries 4). Interestingly, upon increasing the reaction time from 12h to 18h, the maximum yield of 93% was obtained (Table 1, entries 6). Indeed, complex II produces a moderate yield of 78% under similar reaction conditions. Based on the experimental result, it was observed that, indeed, the base plays a key role in the catalyst activation process toward the formation of alkylated amine products. However, the activation of the catalyst was found to be the most effective using KOtBu as compared to other inorganic and organic bases (KOH, Cs2CO3, and Et3N) exploited in these catalytic reactions (Table 1, entries 8, 9, 10). Table 1. Screening of catalytic conditionsa aReaction condition: 2-aminopyrimidine (0.5 mmol), benzyl alcohol (0.55 mmol), catalyst (0.005 mmol, 1mol%), bases (0.25 mmol), and solvent refluxed at given temperature (Silicon oil-bath temp) and time. bIsolated yield. Generality and evaluation of substrate scope of the reaction The inventors of the present invention found that pyrimidine-based amines are considered to be one of the privileged scaffolds and have given a significant contribution in the fields of bio-organic and medicinal chemistry. However, only a few reports were investigated on synthesizing pyrimidine-based N-alkylated amine moieties under the borrowing hydrogen catalytic condition. The inventors of the present invention have successfully demonstrated the substrate scope of the reaction by catalyzing the N-alkylation reaction of amine using alcohol as an alkylating agent, namely the borrowing hydrogen (BH) (or hydrogen auto-transfer) methodology by using the said complex I as catalyst to evaluate the substrate scope of the catalytic reaction that has given a potential product yield has been described below. In one of the preferred embodiments, the inventors of the present invention evaluated the substrate scope of the reaction by using standard reaction conditions to catalyze 2-aminopyrimidine with a range of benzyl alcohol derivatives, leading to selective monoalkylated amine products in appreciable yields referred to in Table 2. Table 2. (NN)MorCoBr2 catalyzed N-alkylation of 2-aminopyrimidine with alcohols.a aReaction conditions: 2-aminopyrimidine 1a (0.5 mmol), alcohols 1c (0.55 mmol), complex I (0.005mmol), and KOtBu (0.25 mmol) refluxed at 130 °C (oil-bath temperature) in 2 mL of toluene for 18h.bIsolated yield. Moreover, aminoquinoline is a derivative of quinoline, and the most notable feature is its use as an antimalarial drug. Further, aminoquinoline represents the most common nitrogen-containing heterocycles found in bioactive natural products and pharmaceutical drug candidates mainly for their anti-malarial, antibacterial, and anticancer activities. For example, 8-aminoquinoline-derived antimalarial agents, such as pamaquine and primaquine, have attracted much interest as chemotherapeutic and prophylactic agents against the liver. During the COVID-19 pandemic, 4- aminoquinoline-based Chloroquine (Aralen) and hydroxychloroquine (Plaquenil) drugs were repurposed and initially authorized by the FDA. Therefore, efficient methods for directly introducing diverse functionalities on aminoquinolines are gaining interest in modern drug discovery. Furthermore, Complex I for the coupling of various alcohols (primary, secondary, aromatic, and aliphatic alcohols) with 6-aminoquinoline to provide a pharmaceutically active secondary amine product in an excellent yield, as disclosed in Table 3. In another embodiment, the inventors of the present invention evaluated the substrate scope of the reaction by using standard reaction conditions to catalyze (NN)MorCoBr2 catalyzed N-alkylation of 6-aminoquinoline with alcohols.a

[0002] Table 3. (NN)MorCoBr2 catalyzed N-alkylation of 6-aminoquinoline with alcohols.a aReaction conditions: 6-aminoquinoline 1d (0.5 mmol), alcohol 1c (0.55 mmol), Complex I (0.005mmol), and KOtBu (0.25 mmol) refluxed at 130 °C (silicon oil- bath temperature) in 2 mL of toluene for 18h.bIsolated yield. In yet another embodiment, the inventors of the present invention have highlighted the synthetic utility of the procedure, wherein the present catalytic reaction conditions can be successfully applied to more challenging aliphatic alcohols, as referred to in Table 4. Table 4. (NN)MorCoBr2 catalyzed N-alkylation of 6-aminoquinoline with Aliphatic alcohol.a aReaction conditions: 6-aminoquinoline 1d (0.5 mmol), alcohols 1c (0.55 mmol), Complex I (0.005mmol), and KOtBu (0.25 mmol) refluxed at 130 °C (silicon oil- bath temperature) in 2 mL of toluene for 18 h.bIsolated yields. Moreover, in a preferred embodiment, (N,N)MorCoBr2catalyzed one pot chemo selective transfer hydrogenation with N-alkylation of 8-aminoquinoline with benzyl alcohol has also been experimented. However, the alkylation of 8-aminoquinoline appeared difficult due to the chelation of both the starting material and the product to the metal, which led to the potential deactivation of the catalyst. However, these substrates were also effectively alkylated under the present catalytic system, and the corresponding N-alkylated amine 70 (61%) was isolated in high yields. Additionally, a diverse byproduct 71 (27%) was obtained via tandem chemo-selective transfer hydrogenation and N-alkylation under excess alcohol case, which describes the role of 8-aminoquinoline as a coordinating ligand and overall reflecting the higher activity of Complex I relative to the well-defined catalysts reported in Table 5. Table 5. (NN)MorCoBr2 catalyzed one pot chemo-selective transfer hydrogenation with N-alkylation of 8-aminoquinoline with benzyl alcohol.aol), Complex I (0.01mmol), and KOtBu (0.25 mmol) refluxed at 130 °C (silicon oil-bath temperature) in 2 mL of toluene for 24h.bIsolated yield. In yet another embodiment, the inventors of the present invention explored aminopyridine-based mono-alkylated amines, which also were primarily used as intermediates in various drug development processes, as mentioned in Table 6. Hence, the utility of the catalyst in the coupling of various alcohols with amines to provide a pharmaceutically active secondary amine product in an excellent yield. Table 6. (NN)MorCoBr2 catalyzed N-alkylation of 3-Aminopyridine with alcohols.a aReaction conditions: 3-aminopyridine 1f (0.5 mmol), alcohol 1c (0.55 mmol), Complex I (0.005 mmol), and KOtBu (0.25 mmol) refluxed at 130 °C (silicon oil- bath temperature) in 2 mL of toluene for 18h.bIsolated yields. Further, in a preferred embodiment, the inventors of the present invention also provide a protocol for the synthesis of quinoline by using Complex I as a catalyst for the said N-alkylation reaction. The aromatic N-heterocyclic compounds are prevalent and widely found in various natural products and bioactive molecules. Among them, quinoline moieties are considered the privileged scaffolds in synthetic chemistry. Thus, the development of an efficient strategy for direct synthesis has attracted great interest in the synthetic methodology. Selective synthesis of 2-substituted quinolines derivatives was attained via the oxidative coupling of 2-aminobenzyl alcohol with acetophenone as model substrates via an acceptorless dehydrogenation process referred to in Table 7. Table 7. (NN)MorCoBr2 catalyzed synthesis of quinoline via ADC.aaR nol 1h (0.55 mmol), Complex I (0.005 mmol), and KOtBu (0.25mmol) refluxed at 130 °C (silicon oil-bath temperature), in 2 mL toluene for 6h.bIsolated yields. Certain specific aspects and embodiment of the present invention will be explained in detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the invention in any manner. EXAMPLES: Herein, all catalytic experiments were conducted in oven-dried glassware under an atmosphere of argon. The reagents were commercially obtained from Sigma Aldrich, TCI, and Alfa Aesar. All solvents were reagent grade or better. Toluene was refluxed over sodium / benzophenone, then distilled in an under-argon atmosphere and stored over sodium. Chemicals used in catalysis reactions were purified using standard procedures (Perrin and Armarego, 1988, Purification of laboratory chemicals, Pergamon Press). Thin layer chromatography (TLC) was performed using silica gel pre-coated aluminium foil, which was visualized with UV light at 254 nm or under iodine. Column chromatography was performed with SiO2 (Silicycle Siliaflash F60 (230- 400 mesh). The UV-visible absorption spectra were recorded with an Agilent Cary 3500 Compact UV-Vis Spectrophotometer.1H NMR spectra were recorded on Bruker Avance 400 spectrometers operating at 400 MHz.13C NMR spectra were recorded on Bruker Avance 400 spectrometers operating at 101 MHz. All1H and13C NMR chemical shifts are reported in ppm relative to SiMe4, which was referenced using known chemical shifts of the solvent as an internal standard.1H NMR data for diamagnetic compounds are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, pent = pentet, sept = septet, br = broad, m = multiplet, app = apparent, obsc = obscured), coupling constants (Hz), integration. High-resolution mass spectra (HRMS) were recorded by Electrospray ionization (ESI) technique on an Agilent Mass Spectrometer (6200 series TOF / 6500 series Q- TOF B.08.00) by infusing sample directly into the source using the automatic method. The detection of gases (H2, m / z= 2) was determined using an online MS with an OmniStarTMGas Analysis System GSD 320 (Pfeiffer) quadrupole mass spectrometer apparatus. Single crystals suitable for X-ray diffraction were coated with Paratone-N, transferred to a nylon loop, and then quickly transferred to the goniometer head of a Bruker SMART APEX DUO diffractometer equipped with a molybdenum X-ray tube (λ = 0.71073 Å) and a Cu Xray tube (λ = 1.54178 Å). Preliminary data revealed the crystal system. The data collection strategy was optimized for completeness and redundancy using the Bruker COSMO software suite. The space group was identified, and the data were processed using the Bruker SAINT+ program and corrected for absorption using SADABS. All the crystal structures were solved by direct methods using SHELXS-97 (Dolomanov et al., 2009, Journal of Applied Crystallography, 42: 339–341) and refined by full-matrix least squares method using SHELXL-97 as well as Olex 2.0 (Sheldrick, 2015, Acta Crystallographica, C71: 3- 8). Amines and alcohols were acquired directly from Sigma-Aldrich, TCI, and Alfa Aesar. Cobalt(II) bromide (CoBr2) was sourced from Sigma-Aldrich while the laboratory synthesized the N,N-bidentate ligands and further the requisite complex. Additional reagents, such as potassium tert-butoxide (KOtBu) and solvent toluene, were also procured from Sigma-Aldrich. EXAMPLE 1. SYNTHESIS OF CO-COMPLEXES: 1.1). Synthesis of 4-(pyridine-2-ylmethyl) morpholine (NNMor(L1)) . . Synthesis of 4-(pyridine-2-ylmethyl)morpholine (NNMor(L1) has been done by suspending 2-(chloromethyl)pyridine hydrochloride (0.3 g, 1.8 mmol), morpholine (0.176 g, 1.9 mmol), and potassium hydroxide (0.11 g, 1.9 mmol) in acetonitrile (12 mL), and further the reaction mixture was refluxed for 12 h at 90 °C under N2 atmosphere. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature, and a rotary evaporator removed solvent under vacuum. The resulting residue was extracted with CH2Cl2:H2O, the organic layer dried over Na2SO4, and evaporation of solvent afforded the product (Ligand; L1) as reddish-orange oil. Yield (0.27 g, 85%). IR (KBr): ν = 3431.36, 2945.30, 2835.36, 2046.47, 1643.35, 1452.40, 1112.93, 1026.13, 644.22.1H NMR (400 MHz, CDCl3): δ 8.57 (d, 1H), 7.68 (t, 1H), 7.42 (t, 1H), 7.20 (d, 1H), 3.75 (t, 4H), 3.66 (s, 2H).13CNMR (400 MHz, CDCl3): δ 157.94, 149.24, 136.43, 123.33, 122.14, 66.86, 64.86, 53.70. GC-MS (CHCl3) m / z calculated for C10H14N2O: 178.11 found: 178.11. 1.2). Synthesis of (NN)MorCoBr2bidentate complex I For the synthesis of (NN)MorCoBr2 bidentate Complex I, to a methanol (3 mL) solution of L1 (0.1 g, 5.6 mmol), anhydrous CoBr2 (0.122 g, 5.6 mmol) in methanol (3 mL) was added drop-wise. The reaction mixture was stirred for 3 h at room temperature. The resulting blue solution was filtered; the resulting filtrate was diffused by ether at room temperature and, after two days, afforded blue colour crystals of (NN)MorCoBr2 (complex I) suitable for single crystal X-ray structure analysis. Yield (92%). IR (KBr): ν = 3419.79, 1637.56, 1446.61, 1301.95, 1109.07, 623.01. 1.3) Synthesis of (NN)PyMeCoBr2 bidentate complex II . y p To an acetonitrile (3 mL) solution of ligand (L2) (0.1 g, 5.7 mmol), anhydrous CoBr2(0.126 g, 5.7 mmol) in acetonitrile (3 mL) was added drop-wise. The reaction mixture was stirred for 3 h at room temperature. The resulting precipitate was filtered and dried. The precipitate was dissolved in methanol, followed by ether diffusion at room temperature, affording the blue-coloured crystals of complex II in 2 days. Yield (90%). IR (KBr): ν = 3444.87, 1635.44, 1444.68, 1311.59, 1111.00, 866.04, 765.74 (L2 was synthesized based on Balaraman and co-workers Catal. Sci. Tchnol., 2024, 14, 98-109). In yet another aspect, the present invention also characterizes the compound NNMorCoBr2 complex by using various analytical (elemental analysis, high- resolution mass spectrometry) and spectroscopic techniques such as IR, UV–Vis, and1H NMR. The magnetic behaviour of (NN)MorCoBr2was confirmed using the Evans method, suggesting a magnetic moment of 4.3 BM at CoII-center (S = 3 / 2). The complex crystallized in the monoclinic system with the space group C2 / c. The molecular structure of complex I was confirmed further by a single-crystal X-ray diffraction study, as shown in FIG. 5. The X-ray diffraction analysis reveals that complex (I) displayed four coordinated, distorted tetrahedral (Td) geometry with two nitrogen donor atoms of ligand (L1) and two bromide ions. The bond angle of N(1)- Co(1)-N(2), N(2)-Co(1)-Br(2), N(1)-Co(1)-Br(2), N(2)-Co(1)-Br(1), N(1)-Co(1)- Br(1) and Br(1)-Co(1)-Br(2) are found at 83.43(9)°, 123.41(7)°, 107.91(7)o, 106.63(7)o, 113.00(7)oand 117.50(3)orespectively. EXAMPLE 2. CHARACTERIZATION OF (NN)MORCoBr2 COMPLEX (I): 2.1. Absorption spectra analysis The UV-visible absorption spectra of metal complexes were recorded in acetonitrile at 298 K. The (NN)MorCoBr2(I) exhibits the absorption band at 210 nm, 205 nm, 212 nm, and 308 nm in UV and 564 nm, 587 nm, and 660 nm in the visible region as represented in FIG.1. 2.2. NMR analysis1H and13C NMR spectrum of free ligands (L1) were recorded in Deuterated chloroform (CDCl3).1H NMR spectra of ligand (L1) exhibit the aromatic protons that resonate between 8.57 to 7.2 ppm, and the aliphatic ring proton (-CH2) ranges between 3.75 and 3.66 ppm.13C NMR spectrum of free ligand (L1) exhibits the aromatic ring (Ar-C) carbons range between 157.94 to 104.11ppm and aliphatic (- CH2) carbons range between 66.86 to 53.73 ppm and methyl (-CH3) carbons present at 13.54 to 11.04 ppm as presented in FIG.2 and13C NMR spectrum of (L1) can be better understood by referring FIG.3. 2.3. Mass analysis Mass spectra of complex (I) were recorded acetonitrile. The molecular ion peak was observed at 394.8723, 412.9129, 417.8686, and 433.8428 m / z as graphically represented in FIG.4. The detailed crystal data of complex I had been presented in Table 8, the bond lengths of complex I in Table 9, and the bond angles of complex I in Table 10 as follows. Table 8. Crystal Data of Complex I Crystal data Chemical formula C10H14Br2CoN2O Computer programs: Bruker APEX2, Bruker SAINT, SHELXS97 (Sheldrick, 2008), SHELXL2018 (Sheldrick, 2018), Bruker SHELXTL, Olex21.5 (Dolomanov et al., 2009). Table 9. Bond Lengths of Complex I Atom Atom Length / Å Atom Atom Length / Å Br1 Co1 2.3520(6) N2 C9 1.486(4) 4) 5) 6) 6) 5) 4) 5) 5) Table 10. Bond Angles of Complex I Atom Atom Atom Angle / ˚ Atom Atom Atom Angle / ˚ Br1 Co1 Br2 117.50(3) C10 N2 C6 109.9(3) 2.4. Evans Method: Magnetic moment calculation and determination of the number of unpaired electrons in the complex I. Evans’ method of1H-NMR was performed to determine the number of unpaired electrons (spin state) in complex I at room temperature. A WILMAD® coaxial insert (with a sealed capillary) tube containing only CDCl3solvent (with 0.1% TMS) was inserted into the normal NMR tubes containing the complex I (4.0 mM, with 0.1% TMS). The present invention have calculated the chemical shift value of the TMS peak in the presence of complex I with respect to that of the TMS peak in the outer NMR tube. The magnetic moment was calculated using the given equation, Where f = oscillator frequency (MHz) Δν = 0.13*400 = 52 HZ T= absolute temperature μeff = 4.3BM M= molar concentration of complex 3 unpaired electron Δν= difference in frequency (Hz) between the two TMS signals The calculated magnetic moment of complex I was determined to be 4.3 BM in CDCl3 at RT, suggesting 3 unpaired electrons in the Co2+centre of complex I as graphically presented in FIG.6. EXAMPLE 3. OPTIMIZATION STUDIES: In this example, the present invention conducted optimization studies to enhance the efficiency of the N-alkylation reaction using cobalt (II) bidentate complexes. The optimization parameters included screening various cobalt bidentate complexes, solvents, reaction temperatures, base, base amount and quinoline synthesis. The goal was to identify the optimal conditions that maximize the yield and selectivity of the desired product. 3.1. Optimization studies for N-alkylation reaction Table 11: Screening of Cobalt bidentate complexaCo H 2O Entry Complex Yield (%) aReaction condition: 1a (0.5 mmol), 2b (0.55 mmol), Co-complex (1 mol%) and KOtBu (0.25 mmol) refluxed in toluene at 130oC (silicon oil-bath) temperature.bIsolated yield in 12 h.cIsolated yield in 18 h. Table 12. Screening of Solventa 1 N t 45aReaction condition: 1a (0.5 mmol), 2b (0.55 mmol), (NN)MorCoBr2 (1 mol%) and KOtBu (0.25 mmol) using 2 mL of solvent refluxed at 130oC (silicon oil- bath) temperature for 18 h.bIsolated yield. Table 13. Screening of Temperaturea p 4 100 54 5 120 78aReaction condition MorCoBr2 (1 mol%) and KOtBu (0.25 mmol) refluxed in toluene at different (silicon oil-bath) temperatures. bIsolated yield. Table 14. Screening of Basea aReaction condition: 1a (0.5 mmol), 2b (0.55 mmol), (NN)MorCoBr2 (1 mol%) and base (0.25 mmol) refluxed in toluene at 130oC (silicon oil-bath) temperatures. bIsolated yield. Table 15. Screening of Base amounta 1 0.05 34aReaction condition: . , . ,MorCoBr2(1 mol%) and KOtBu refluxed in toluene at 130 °C (oil-bath temperature) for 18 h.bIsolated yield. 3.2. Optimization studies for quinoline synthesis Table 16. Reaction time screening for quinoline synthesisa aReaction condition: 1 N)MorCoBr2 (1 mol%) and KOtBu refluxed in toluene at 130 °C (oil-bath temperature) for 18 h. bIsolated yield. EXAMPLE 4. MECHANISTIC INVESTIGATION: In this example, the present invention delves into a mechanistic investigation comprising three key aspects: H2 detection, deuterium labelling experiments, and radical trapping experiments. Through these experimental approaches, the present invention aims to elucidate the underlying mechanisms governing the catalytic behaviour of the cobalt (II) bidentate complexes in various reactions. By probing the reaction intermediates and pathways, a deeper understanding of the catalytic process can be achieved, facilitating further optimization and application of the present invention. 4.1. H2 detection In an oven-dried screw cap reaction tube (15 mL), 3-pyridine methanol (0.5 mmol), KOtBu (0.25 mmol), (NN)MorCoBr2 (1 mol%), and toluene (2 mL) were added in a gentle stream of argon as represented in the Scheme S4. Then, the reaction mixture was stirred with a magnetic stirring bar at 130 °C for 18 h. After completion of the reaction, the crude mixture was cooled to room temperature, followed by the sample submitted for gasometer analysis for detection of H2 gas as systematically represented in the FIG.7. . . 4.2. Deuterium labelling experiments In two oven-dried 15 mL screw-capped vials, one with 3-aminopyridine (0.5 mmol), and the other with 6-aminoquinoline and in both vials, 4-methoxybenzyl (deuterated) alcohol (0.55 mmol), (89%) as graphically presented in FIG. 8, KOtBu (0.5 mmol), (NN)MorCoBr2 (1 mol%) were added in toluene under a gentle stream of argon. Then the reaction mixture was stirred for 18 h at 130 °C as represented in Scheme S5. After completion of the reaction, the crude mixture was filtered through a celite and washed with methanol, followed by solvent removal under vacuum. The residue was purified by column chromatography on silica gel (eluent: pet ether) to afford the 72% and 47% yield of N-alkylated deuterated products represented graphically in FIG.9 and FIG.10.

[0003] 4.3. Mercury Test / Homogenous Test To an oven-dried 15 mL screw-capped reaction tube, benzyl alcohol (0.55 mmol), 3- aminopyridine (0.5 mmol), KOtBu (0.25 mmol), (NN)MorCoBr2(1 mol%), and mercury (2 eq, 1 mmol) were added in toluene under a gentle stream of argon. Then, the reaction mixture was stirred for 18 h at 130 °C (oil-bath temperature). After completion of the reaction, the crude mixture was cooled to room temperature, filtered through a celite pad with several washings (3 x 3 mL methanol), and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: pet ether / ethyl acetate) to yield the desired product in 62% as shown in the Scheme S6. c eme . omogenous es . 4.4 Radical trapping experiments To an oven-dried 15 mL screw-capped reaction tube, benzyl alcohol (0.55 mmol), 3- aminopyridine (0.5 mmol), KOtBu (0.25 mmol), (NN)MorCoBr2 (1 mol%), and TEMPO / BHT (1 eq) were added under a gentle stream of argon. Then the reaction mixture was stirred for 18 h at 130 °C. After completion of the reaction the crude mixture was cooled to room temperature followed by filtered through a celite pad with several washings (3 x 3 mL methanol) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: pet ether / ethyl acetate) to afford the desired product in 73 / 67% yield as represented in the Scheme S7. Sch pecies.

Claims

We claim:

1. A process for the preparation of (NN)MorCoBr2 bidentate complex I of formula I, comprising the(i) reacting 2-(chloromethyl) pyridine hydrochloride of formula IVwith morpholine of formula III in the presence of a base in(ii) cooling the reaction mixture and removing the solvent under vacuum, the resulting residue was extracted with a solvent and water mixture; (iii) drying the organic layer over a salt and evaporating the solvent to obtain the compound of formula II; (iv) reacting the compound of formula II with anhydrous CoBr2in the presence of a solvent; and (v) filtering the above solution to obtain the compound of formula I.

2. The process, as claimed in claim 1, wherein step (i) is conducted at temperatures ranging from 75-105 °C for a duration of 5-15 hours under the N2 atmosphere.

3. The process, as claimed in claim 1, wherein the compound of formula II is 4-(pyridine-2-ylmethyl)morpholine (N,NMor(L1)).

4. The process, as claimed in claim 1, wherein the base in step (i) is selected from a group comprising calcium hydroxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, trimethylamine, sodium tert-butoxide, potassium hydride, and barium hydroxide.

5. The process, as claimed in claim 4, wherein the base in step (i) is potassium hydroxide.

6. The process, as claimed in claim 1, wherein the solvent in step (i) is selected from a group comprising acetone, methanol, ethanol, ethyl acetate, acetonitrile, isopropanol, butanol, and mixtures thereof.

7. The process, as claimed in claim 6, wherein the solvent in step (i) is acetonitrile.

8. The process, as claimed in claim 1, wherein the solvent used in step (ii) is selected from a group comprising chloroform, dichloromethane, acetonitrile, diethyl ether, dimethyl formamide, dimethoxy ethane, dimethyl acetamide, dioxane and mixtures thereof.

9. The process, as claimed in claim 8, wherein the solvent used in step (ii) is dichloromethane.

10. As claimed in claim 1, the salt used in step (iii) is selected from a group comprising sodium hydroxide, sodium chloride, sodium sulfate, sodium fluoride, sodium bromide, sodium iodide, and sodium bicarbonate.

11. The process, as claimed in claim 10, wherein the salt used in step (iii) is sodium sulfate.

12. The process, as claimed in claim 1, wherein step (iii), the yield of the compound of formula II is 85%.

13. The process, as claimed in claim 1, wherein the solvent used in step (iv) is selected from a group comprising methanol, ethanol, methyl acetate, heptane, hexane, and diethyl ether.

14. The process, as claimed in claim 13, wherein the solvent is methanol.

15. The process, as claimed in claim 1, wherein the yield of the compound of formula I obtained in step (v) is 92%.

16. A (NN)MorCoBr2bidentate complex I of formula Ias claimed in claim 1.

17. A process for preparing N-alkylated heterocyclic amines in the presence of the compound of formula Ireacting heterocyclic amines with alcohols in the presence of a compound of formula I, a base, and a solvent.

18. The process, as claimed in claim 17, wherein the heterocyclic amines are selected from the group comprising aminopyrimidine, aminoquinoline, aminopyridine, or derivatives thereof.

19. As claimed in claim 17, the base is selected from a group comprising calcium carbonate, potassium hydroxide, cesium carbonate, potassium tert-butoxide, sodium tert-butoxide, potassium hydride, trimethylamine, or mixtures thereof.

20. The process, as claimed in claim 19, wherein the base is potassium tert- butoxide.

21. The process, as claimed in claim 17, wherein the solvent is selected from a group comprising xylene, toluene, tetrahydrofuran, n-octane, ethyl acetate, butyl acetate, 1,4 dioxane, cyclohexane or mixtures thereof.

22. The process, as claimed in claim 21, wherein the solvent is toluene.

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