TRANSITION METAL-FREE EFFICIENT SYNTHESIS OF BIS(INDOLYL)PROPYNES(BIPS) AND DERIVATIVES THEREOF

Abstract

ABSTRACT The present invention relates to a process (300) for the synthesis of BIPS and derivatives thereof. The process (300) involves reacting a solution of 3-phenylpropiolaldehydes in anhydrous Acetonitrile (ACN) with indole under a catalyst (iodine) to obtain a reaction mixture followed by neutralization, extraction, drying, and purifying of a crude product of BIP. Figure 3

Specification

Description:FORM 2
The Patents Act 1970
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The Patent Rules 2003
COMPLETE SPECIFICATION
(See Section 10 and rule 13)
1. TITLE: Transition Metal-free Efficient Synthesis of Bis(indolyl)propynes(BIPs) and derivatives thereof
2. APPLICANT:
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Baba Farid College INDIA House No. Muktsar Road, Bathinda-153001, Punjab, India
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Baba Farid College of Engineering and Technology INDIA House No. Muktsar Road, Bathinda-153001, Punjab, India
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3. PREAMBLE OF THE DESCRIPTION: The following COMPLETE specification particularly describes the invention and the manner in which it is performed.

CROSS-REFERENCE TO RELATED DISCLOSURE
Cross-reference of the present disclosure is made to a research paper referenced as "Manpreet Singh and et.al, Transition Metal-free Efficient Synthesis of Bis(indolyl)propynes (BIPs), Org. Biomol. Chem., 2024, DOI: 10.1039/D4OB01017E."
FIELD OF INVENTION
The present disclosure generally relates to chemical processes. More specifically, the present invention relates to a transition metal-free efficient synthesis of Bis(indolyl)propynes(BIPs) and derivatives thereof.
BACKGROUND OF THE INVENTION
The synthesis of bis(indolyl)methanes (BIMs) has garnered significant attention in organic synthesis due to their potential pharmacological properties including anticancer,1 anti-neurodegenerative, antifungal, anti-inflammatory, antioxidant, antibacterial and antimicrobial. Bis(indolyl)methane-based scaffolds such as arundine and arsindoline A have been harnessed in cancer chemotherapy, while vibrindole A exhibits remarkable antibacterial properties. Bis-indolyle based alkaloids are not only effective in treating cancer but also hold promise in cancer prevention by altering the cancer-causing estrogen metabolites. Topsentine B1, extracted from the Mediterranean sponge Topsentia genitrix, featuring two indole rings exhibit anti-proliferative effects against NSCLC-N6 and HeLa cells, with IC50 values of 4.4 µM. Recently, BIM derivatives have also been found to bind the allosteric pocket of the Kinesin Eg. In addition to this, BIM derivatives have also been utilised as dyes and chemosensors.
At the same time, alkynes moiety is also known for its versatile adaptability and robust reactivity, making it among the most valuable chemical motifs in current organic synthesis. Interestingly, alkyne based natural products have been discovered as anti-Alzheimer, antibiotic, and antitumor agents and their antitumor effect is due to the sequence-specific intercalation into chromosomal DNA, inducing cell apoptosis and killing tumour cells.
Inspired by such a class of compounds, it was envisaged to amalgamate these two privileged scaffolds via synthesis of bis(indolyl)propyne (BIP) derivatives.
There are conventional arts which are available on synthesis of BIMs. However, Bis(indolyl)propynes (BIPs) may be used as a chemosensor for detection of heavy metal ions and drug molecules for further used in medicinal chemistry, better than that of BIMs. Additionally, in the case of Bis(indolyl)propynes (BIPs), the presence of an alkyne moiety-rather than the methylene group found in Bis(indolyl)methanes (BIMs)-is directly attached to the carbon positioned between two indole units. Such a structural feature of BIPs offers potential for further cyclization with the aromatic rings of the indole, or interaction with nucleophiles, such as sulfur insertion, to generate valuable heterocyclic compounds. These transformations could lead to the development of new drug candidates. Additionally, alkyne-containing natural products have been identified with anti-Alzheimer, antibiotic, and antitumor properties. As such, the current compounds with alkyne groups may hold promise for the development of novel therapeutics, particularly for the treatment of Alzheimer's disease.
In BIPs, alkyne moiety is directly attached to a carbon positioned between two indoles, exhibiting potential for further cyclization with the aromatic rings of the indole or with nucleophiles, such as through sulfur insertion to generate drug importance (as shown in Figure 1). With potential optoelectronic properties and medicinal significance, BIPs may be further utilized to convert polyaromatic compounds through cyclization with the alkyne moiety, potentially finding applications in optoelectronics.
There is one conventional art which discloses synthesis process for BIPs by Chinta group Such a process involves reacting N-alkyl indole-3-carbaldehyde with lithium acetylides under metal-containing, pyrophoric conditions at low temperature (as shown in Figure 2). Such a process has certain limitations such as pyrophoric conditions at low temperatures, thereby making such a conventional process difficult to handle. Also, the conventional art involves the use of bases and transition metals (such as CuBr and DMEDA) for the synthesis of indolylalkynamines, which may be inefficient. In addition, the reaction process takes a long time (9 hours) to complete.
Therefore, there exists a need for developing a synthesis process for BIPs which gets rid of aforementioned issues.
OBJECTS OF THE INVENTION
A primary object of the present disclosure relates to provide a process for the synthesis of BIPs and derivatives thereof.
Another object of the present disclosure is to provide a transition metal-free synthesis process for BIPs and derivatives thereof.
Another object of the present disclosure is to provide the process for the synthesis of BIPs which yields BIPs and derivatives thereof up to 96%.
Another object of the present disclosure is to provide the process for the synthesis of BIPs and derivatives thereof which takes very short time to complete i.e. between 20-40 minutes.
Another object of the present disclosure is to provide the process for the synthesis of BIPs and derivatives thereof which provides a scope of further conversion of the yielded BIPs into polycyclic aromatic compounds.
Another object of the present disclosure is to provide the process for the synthesis of BIPs and derivatives thereof which is of utmost importance to materials science and pharmaceuticals.
Another object of the present disclosure is to provide the process for the synthesis of BIPs and derivatives thereof which is independent of pyrophoric conditions at low temperatures.
Another object of the present disclosure is to provide the process for the synthesis of BIPs and derivatives thereof which is environment friendly due to green catalyst- iodine.
Another object of the present disclosure is to provide the process for the synthesis of BIPs and derivatives thereof which is easy to handle as per reaction conditions at ambient temperature or room temperature
Another object of the present disclosure is to provide the process for the synthesis of BIPs and derivatives thereof which has short reaction time achieves completion within 20-40 minutes for all derivatives.
SUMMARY OF THE INVENTION
In one aspect of a present invention, a process (300) for the synthesis of BIPS and derivatives thereof. The process (300) involves reacting a solution of 3-phenylpropiolaldehydes in anhydrous Acetonitrile (ACN) with indole under a catalyst to obtain a reaction mixture, followed by neutralization, extraction, drying, and purifying of a crude product of BIPs and derivatives thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
Other objects, features, and advantages of the embodiment will be apparent from the following description when read with reference to the accompanying drawings. In the drawings, wherein like reference numerals denote corresponding parts throughout the several views:
Referring to Figure 1, shows a chemical structure of Bis(indolyl)propynes (BIPs);
Referring to Figure 2, shows a conventional schematic reaction process for the synthesis of BIPs;
Referring to Figure 3, shows a schematic reaction process (300) for the synthesis of BIPs, in accordance with an embodiment of a present disclosure;
Referring to Figure 3A, shows a reaction scheme 1 for the synthesis of a,ß-unsaturated acetylenic aldehydes, in accordance with the embodiment of the present disclosure;
Referring to Figure 3B1 to 3B50, enlists all the possible 50 derivatives of BIPs, synthesized through the process (300), in accordance with another embodiment of the present disclosure;
Referring to Figure 3C, shows Gram scale synthesis of BIP (12a), in accordance with the embodiment of the present disclosure;
Referring to Figure 3D, shows scope of reaction of BIP with 3-methyl indole (q), in accordance with the embodiment of the present disclosure;
Referring to Figure 3E1 and 3E2, show control experiment reaction schemes in presence of TEMPO as well as BHT using model substrates; BIP (12), indole (a) and I2 (5 mol%), in accordance with the embodiment of the present disclosure; and
Referring to Figure 3F, shows a complete reaction mechanism for the formation of BIPs, in accordance with the embodiment of the present disclosure.
Table
Table 1 shows optimization studies for the formation of 3,3'-(3-phenylprop-2-yne-1,1-diyl)bis(1H-indole).
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The present disclosure discloses a process (300) for the synthesis of BIPS, chemical structure thereof as shown in Figure 1. Figure 3 shows a reaction scheme for the process (300). The process (300) involves stirring 9-10 wt% of solution of 3-phenylpropiolaldehydes in anhydrous Acetonitrile (ACN), followed by adding 15-20 wt% of indole and and 0.4-0.5 wt% of an iodine catalyst to the stirred solution to obtain a reaction mixture, followed by stirring the reaction mixture obtained at room temperature for 20-35 minutes at 600-800 RPM. Then, the process (300) involves monitoring the reaction mixture through Thin Layer Chromatography (TLC), followed by quenching the reaction mixture with aqueous solution of sodium thiosulphate and extracting thereto and drying the extracted contents and concentrating thereto under reduced pressure in the range of 760-800 mm Hg to yield crude product of BIPs and purifying thereto. The process (300) is free of transition metals.
Experimental details
With reference to Figure 3A, the present disclosure involve the process (300) that commenced with the gram-scale synthesis of a,ß-unsaturated acetylenic aldehydes 12-22 from diversely substituted gem-dibromolefines 1-11a which were in turn prepared from aldehydes 1-11 via application of Corey-Fuchs reaction. The resulting acetylenic aldehydes 12-22, were obtained in 44-84% yields (Scheme 1 as shown Figure 3A).
After the successful synthesis of acetylenic aldehydes 12-22; 3- phenylpropiolaldehyde (12) (Table 1) and 1H indole (a) were selected as the model substrates to optimize reaction conditions for the synthesis of BIP, 3,3'-(3-phenylprop-2-yne-1,1-diyl)bis(1H-indole) (12a). Initially, a reaction was conducted in presence of 20 mol % of p-TSA in acetonitrile (ACN) at room temperature using 3.0 equivalents of indole and within 5 min, the TLC examination revealed the formation of a violet-coloured product visible to the naked eyes. Such a product was isolated in 34% yield after column chromatographic purification (Table 1, entry 1). The spectroscopic analysis confirmed that the obtained product is indeed 3,3'-(3-phenylprop-2-yne-1,1-diyl) bis(1H-indole) 12a, as expected. When the same reaction was examined at room temperature in the presence of 10 mol % of p-TSA in ACN with 2.5 equiv. of indole, it delivered the anticipated product in 85% yield (Table 1, entry 2). Next, another reaction was conducted in presence of 15 mol % of p-TSA in THF at room temperature with 2.0 equiv. of 1H indole which generated the desired product 12a in 85% yield (Table 1, entry 3). Similarly, a reaction with 2.0 equiv. of indole with 10 mol % of p-TSA in THF readily generated the desired product 12a in 80% yield which revealed that 2.0 equiv. of indole was sufficient for completion of reaction without affecting the reaction yield (Table 1, entry 4). Similar output was noted when the reaction was examined with 10 mol% of I2 in THF or ACN; however, only 25 min were required for completion of reaction in ACN (Table 1, entry 5-6). Interestingly, a reaction of 12 with 2.0 equiv. of indole in the presence of 5 mol % of iodine in ACN at ambient temperature afforded the anticipated product 12a in 96% yields within 35 min (Table 1, entry 7). Subsequently, a reaction was investigated with 5 mol % of I2 in THF but the yield was reduced to 70% showing that ACN was more suitable solvent than THF (Table 1, entry 8). Next, the reactions were investigated with 5 mol % of I2 in DCM, EtOH and 1,4-dioxane, but the desired product was obtained in 60%, 70% and 75% yields, respectively (Table 1, entry 9-11). No reaction was observed in the absence of iodine in ACN highlighting the significance of iodine as a catalyst (Table 1, entry 12). Interestingly, a reaction in aqueous medium in presence of AcOH (10 mol %) secured the product in 83% yield but under heating conditions (Table 1, entry 13). However, when reaction was investigated in ACN in presence of AcOH (10 mol %), the product yield was low (60%, Table 1, entry 14). Surprisingly, a reaction with CuBr/CuI or KI as a catalyst failed to deliver any product (Table 1, entries 15-17). Further, a reaction was executed with 2.0 equiv. of base (Cs2CO3/Et3N) but the encouraging results were not obtained (Table 1, entries 18-19). Similarly, poor results were obtained with AgOT in DCM (Table 1, entry 20). To verify the impact of temperature on yield; a reaction was analysed at 0 oC wherein the desired product was smoothly afforded in 88% yields. The rate of reaction was significantly slow at 0 deg C and took 2 h for completion (Table 1, entry 21) while same reaction at 50 deg C was completed within 15 min but the product was obtained in 60% yields only and polar impurities were formed (Table 1, entry 22). From the above experimental results, it was concluded that 5 mol % of I2 in ACN at room temperature was the optimal condition for the preparation of bis(indolyl)propynes (BIPs) 12a via reaction of acetylenic aldehydes (1.0 equiv.) with indole (2.0 equiv.)
With optimization conditions in hand, scope and generality of the process (300) was evaluated by using diversely substituted aromatic acetylenic aldehydes 12-20 for reaction with indoles a-p (Scheme 2). It is noteworthy to mention that all the acetylenic aldehydes 12-20 turned out to be suitable precursor for this transformation and worked commendably with electron rich as well as electron deficient indoles a-p under optimal conditions to furnish the anticipated bis(indolyl)propyne derivatives; Figures 3B1 to 3B50 in 58-96% yields within 20-40 min. It was observed that indole with free NH as well as having substitution at N-1 and C-2 position reacted well with diversely substituted aromatic acetylenic aldehydes 12-20. Next, the scope of the strategy was investigated with aliphatic acetylenic aldehydes 21-22 for reaction with diverse indoles a c-e, h, k, n, o bearing electron rich as well as electron deficient substituents to afford the desired BIPs in good yields (40-77%). It was found that relatively low yield (40- 68%) was recorded in case of 5-bromo indole though reaction was completed within 20-40 min. A library of 50 BIPs was generated using the versatility of iodine and all the products were readily purified by silica gel column chromatography (60-120 mesh).
To further enhance the scope of the strategy, a gram scale synthesis of BIPs was investigated for the reaction of phenylpropioleldehyde (12) with 2.0 equiv. of indole (a) (Figure 3C). The reaction was completed within 35 minutes to afford 3,3'-(3-phenylprop-2-yne-1,1-diyl)bis(1H-indole) (12a) in 94% yields. When the reaction of 3-phenylpropiolaldehyde (12) was performed with 3-methyl indole (q) under optimal conditions, no progress was observed even after 16 h of reaction time and model substrates remained intact (Figure 3D). It is also pertinent to mention that reaction of indole (a) with phenyl propiolic acid and 3- phenylprop-2-yn-1-ol was also investigated under standard conditions but no reaction was observed. CHO + N H 12 q I2 (5 mol%), ACN, rt, 16h CH3 No Reaction Scheme as show in Figure 3D.
Scope of reaction with 3-methyl indole.
To investigate the possibility of a free radical pathway, control experiments were conducted in presence of TEMPO as well as BHT using model substrates; 3-phenylpropiolaldehyde (12), indole (a) and I2 (5 mol%). It was found that the reaction progressed smoothly in presence of TEMPO (1.0 equiv.) to furnish the anticipated product 12a in 87% yields within 35 min (Figure 3E1). Similarly, a reaction in presence of BHT (butylated hydroxytoluene, 1.0 equiv.) afforded the 12a in 82% yield within 35 min (Figure 3E2). These results eliminated the possibility of a free radical mechanism. CHO + N H TEMPO (1.0 equiv.), I2 (5 mol%), ACN, rt, 35 min N H NH 12 a 12a 87% CHO + N H BHT (1.0 equiv.), I2 (5 mol%), ACN, rt, 35 min N H NH 12 a 12a 82% Scheme 6. Control Experiments. On the basis of controlled experiments and previous findings, a plausible mechanism for the formation of BIPs has been depicted in Figure 3F. It is disclosed that iodine coordinates with formyl functionality of acetylenic aldehydes (12) making it more electrophilic to facilitate the attack of indole (a) resulting in formation of intermediates 23-24; indol-3-yl-3-phenylprop-2- yn-1-ol. Further coordination with iodine results in formation of intermediate which upon reaction with 2nd equivalent of indole results in formation of bis(indolyl)propyne derivative as shown in Figure 3B1.
Hence, the present invention achieves a practical synthesis of a series of diversely substituted bis(indolyl)propyne (BIP) derivatives via iodine-catalysed cascade condensation of a,ß-unsaturated acetylenic aldehydes with diversely substituted indoles. Such a process is applicable to gram scale synthesis and a library of 50 molecules being developed with good to excellent yields. The salient features of the reaction involve the synthesis of indole based privileged scaffolds in short reaction time, under transition metal-free conditions, with wide substrate scope and excellent yields under ambient conditions. Iodine as a catalyst exhibited significant advantages over other catalysts in terms of efficiency, reaction time, affordability, and environmental friendliness.
Experimental details
Chemical and reagent were purchased from Sigma Aldrich, Acros, Spectrochem, Avra, GLR Innovations, Merck and used without purification. Anhydrous solvents (ACN, DMF, DCM, THF) which are commercially available were used as such without further distillation and stored in presence of A° molecular sieves. Thin-layer chromatography (TLC) was performed on precoated aluminium plates (E. Merck; silica gel 60 PF254, 0.25 mm). Column chromatography was performed on silica gel (Spectrochem make, 60-120 mesh). IR spectra were recorded on a Bruker FTIR. (Tensor 27) spectrometer. 1H-NMR spectra were recorded on an Jeol spectrometer at operating frequencies of 600 MHz for (1H) and 150 MHz ( 13C-NMR), as shown in the individual spectrum, by using tetramethylsilane (TMS) as a standard. The multiplicity in the 1H-NMR spectra is as follows: s for singlet, d for doublet, t for triplet, q for the quartet, dd for the doublet of the doublet, and m for multiplet. General procedure for the gram-scale synthesis of a,ß-unsaturated acetylenic aldehydes 12-22 as exemplified for 3- phenylpropiolaldehyde. Under an atmosphere of argon, nBuLi (1.2 eq., 0.0231 mol, 1.6 M in n-hexane) was added over a period of 30 minutes via syringe pump to a solution of gemdibromoolefine (1 eq., 0.0193 mol) in anhydrous THF at -78 °C, and the mixture was stirred at -40 °C for 15 minutes. After addition of DMF (2.0 eq., 0.0386 mol) at once, the mixture was allowed to warm to room temperature and stirred for one hour. The mixture was added to a stirring solution of KH2PO4 (aq.)/diethyl ether (1:1). After five minutes, the layers were separated and the aqueous layer was extracted with diethyl ether. The combined organic layers were dried over Na2SO4, the solvent was removed under reduced pressure and the crude product was subjected to column chromatography (hexane/EtOAc, 99:1, v/v).to obtain 3-phenylpropiolaldehyde in 84% yield.
The aqueous layer was extracted with EtOAc (3 x 30 mL), dried over Na2SO4 and concentrated under reduced pressure to get the crude product. The crude product was further purified through silica gel (60-120 mesh) column chromatography (EtOAc/hexane, 1:4 v/v) to afford the corresponding analytically pure product 12a in 94% yield as a dark brown solid. It is mentioned that the product was obtained in 96% yields during milligram scale (100 mg) reaction.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B1):
Isolated yield 96% as a dark brown solid; m.p. 104-106 oC; Rf = .5 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3426, 3051, 2674, 739, 413; 1H NMR (600 MHz, CDCl3) d = 5.75 (s, 1H, CH), 7.09-7.10 (t, J = 7.0 Hz, 2H, ArH), 7.15-7.16 (m, 2H, ArH), 7.17- 7.20 (m, 2H, ArH), 7.27 (t, J = 1.8 Hz, 3H, ArH), 7.35-7.37 (m, 2H, ArH), 7.43-7.45 (m, 2H, ArH), 7.75-7.77 (m, 2H, ArH), 7.98 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = 27.1, 82.0, 90.8, 111.3, 116.3, 119.5, 120.0, 122.2, 122.8, 124.0, 126.5, 127.8, 128.3, 131.9, 136.9 ppm; HRMS (ESI) m/z: calcd. for C25H18N2 [M + H]+ : 347.1543 found 347.1553.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(4-bromo-1H-indole) (Figure 3B2): Isolated yield 74% as a brown solid; m.p. 190-192 oC; Rf = 0.42 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3731, 3424, 2360, 1556, 1034, 458; 1H NMR (600 MHz, CDCl3) d = 6.80 (s, 1H, ArH), 7.07-7.10 (m, 6H, ArH), 7.23-7.25 (m, 5H, ArH), 7.44 (d, J = 9.2 Hz, 2H, ArH), 8.08 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = 28.1, 83.0, 92.5, 110.3, 118.7, 121.2, 123.1, 123.6, 124.6, 124.9, 127.1, 128.0, 128.5, 132.1, 138.6 ppm; HRMS (ESI) m/z: calcd. for C25H16Br2N2 [M + H]+ : 502.9753 found 502.9771.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(5-bromo-1H-indole) (Figure 3B3): Isolated yield 68% as a pale brown solid; m.p. 70-72 oC; Rf = 0.43 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3415, 2933, 2356, 1649, 1015, 936, 742, 672, 443.; 1H NMR (600 MHz, CDCl3) d = 5.62 (s, 1H, CH), 7.19 (d, J = 3.0 Hz, 2H, ArH), 7.24 (d, J = 10.2 Hz, 2H, ArH), 7.27-7.30 (m, 5H, ArH), 7.46 (d, J = 4.2 Hz, 2H, ArH), 7.84 (s, 2H, ArH), 8.11 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = 27.4, 83.6, 90.0, 112.9, 113.0, 115.5, 122.4, 123.5, 124.0, 125.2, 128.0, 128.0, 128.3, 131.8, 135.5 ppm; HRMS (ESI) m/z: calcd. for C25H16Br2N2 [M + H]+ : 502.9753 found 502.9771.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(6-bromo-1H-indole) (Figure 3B4): Isolated yield 80.% a brown solid; m.p. 160-162 oC; Rf = 0.41 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3415, 2933, 2356, 1649, 1015, 936, 742, 672, 443.; 1H NMR (600 MHz, CDCl3) d = 5.66 (s, 1H, CH), 7.13 (s, 2H, ArH), 7.17 (dd, J = 2.1, 10.3 Hz, 2H, ArH), 7.27 (t, J = 3.7 Hz, 3H, ArH), 7.42 (t, J = 8.1 Hz, 2H, ArH), 7.52 (d, J = 2.1 Hz, 2H, ArH), 7.56 (d, J = 10.3 Hz, 2H, ArH), 8.01 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = 26.7, 75.6, 86.1, 113.1, 116.5, 122.8, 124.0, 125.4, 128.3, 135.8 ppm; HRMS (ESI) m/z: calcd. for C25H16Br2N2 [M + H]+ : 502.9753 found 502.9771.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(4-chloro-1H-indole) (Figure 3B5): Isolated yield 92% as a pale brown solid; m.p. 180-182 oC; Rf = 0.39 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3423, 3354, 1986, 1325, 1256, 1180, 903, 693, 458; 1H NMR (600 MHz, CDCl3) d = 5.62 (s, 1H), 7.21-7.23 (m, 2H), 7.26 (d, J = 1.6 Hz, 1H), 7.27 (d, J = 1.6 Hz, 1H), 7.29-7.31 (m, 3H), 7.35 (dd, J = 3.1, 6.6 Hz, 2H), 7.37 (d, J = 0.9 Hz, 1H), 7.38 (d, J = 0.9 Hz, 1H), 7.88 (s, 2H), 10.55 (s, 2H).ppm; 13C NMR (150 MHz, CDCl3) d = 27.2, 83.0, 92.1 110.5, 114.5, 118.8, 123.0, 124.3, 124.5, 125.0, 127.7, 128.2, 131.7, 138.1 ppm; HRMS (ESI) m/z: calcd. for C25H16Cl2N2 [M + H]+ : 415.0763 found 415.0772.
3,3'-(3-phenylprop-2-yne-1,1-diyl)bis(1H-indole-5-carbo-nitrile) (Figure 3B6): Isolated yield 90% as a pale brown solid; m.p. 188- 190 oC; Rf = 0.37 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3455, 3310, 1983, 1327, 1260, 1189, 915, 699, 451; 1H NMR (600 MHz, DMSO-d6) d = 5.62 (s, 1H, CH), 7.21-7.23 (m, 2H, ArH), 7.26 (d, J = 1.6 Hz, 1H, ArH), 7.27 (d, J = 1.6 Hz, 1H, ArH), 7.29-7.31 (m, 3H, ArH), 7.35 (dd, J = 3.1, 6.6 Hz, 2H, ArH), 7.37 (d, J = 0.9 Hz, 1H, ArH), 7.38 (d, J = 0.9 Hz, 1H, ArH), 7.88 (s, 2H, ArNH), 10.55 (s, 2H) ppm; 13C NMR = 13 C NMR spectrum has not been recorded due to its insolubility in CDCl3 as well as DMSO-d6. HRMS (ESI) m/z: calcd. for C27H16N4 [M + H]+ : 396.1375 found 396.1389.
3'-(3-Phenylprop-2-yne-1,1-diyl)bis(5-fluoro-1H-indole) (Figure 3B7): Isolated yield 83% as a pale semisolid ; Rf = 0.37 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3426, 3051, 2674, 1890, 1601, 739, 430; 1H NMR (600 MHz, CDCl3) d = 5.59 (s, 1H, CH), 6.90 (t, J = 8.0 Hz, 2H, ArH), 7.23 (t, J = 10.9 Hz, 6H, ArH), 7.32 (d, J = 11.6 Hz, 3H, ArH), 7.42 (d, J = 11.3 Hz, 2H, ArH), 8.00 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = 27.6, 82.7, 90.1, 105.0, 105.2, 111.0, 111.2, 112.3, 112.4, 116.3, 116.3, 124.0, 124.7, 126.9, 127.0, 128.3, 128.7, 132.1, 133.7, 156.8, 159.9 ppm; HRMS (ESI) m/z: calcd. for C25H16F2N2 [M + H]+ : 383.1354 found 383.1361.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(6-fluoro-1H-indole) (Figure 3B8): Isolated yield 90% as a brownish solid; m.p. 108-110 oC; Rf = 0.38 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3426, 3051, 2674, 1890, 1601, 739, 430; 1H NMR (600 MHz, CDCl3) d =5.65 (s, 1H, CH), 6.82 (t, J = 11.3 Hz, 2H, ArH), 7.02 (d, J = 11.6 Hz, 2H, ArH), 7.11 (s, 2H, ArH), 7.24 (d, J = 8.3 Hz, 3H, ArH), 7.41 (d, J = 8.3 Hz, 2H, ArH), 7.60 (t, J =9.2 Hz, 2H, ArH), 8.00 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = d 27.5, 82.6, 90.5, 97.8, 98.1, 108.6, 108.9, 116.5, 120.9, 121.0, 123.2, 123.2, 123.3, 124.0, 128.3, 128.7, 132.1, 137.0, 137.1, 159.3, 161.6 ppm; HRMS (ESI) m/z: calcd. for C25H16F2N2 [M + H]+ : 383.1354 found 383.1361.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(5-methoxy-1H-indole) (Figure 3B9): Yield: 80% as a cream brown solid; m.p. 100-102 oC; Rf = 0.40 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1= 3371, 3021, 2886, 1726, 1152, 942, 690, 441; 1H NMR (600 MHz, CDCl3) d =3.78 (s, 6H, OCH3), 5.66 (s, 1H, CH), 6.86 (dd, J = 3.0, 10.5 Hz, 2H, ArH), 7.11 (d, J = 3.0 Hz, 2H, ArH), 7.23 (d, J = 3.0 Hz, 2H, ArH),7.25 (s, 2H, ArH), 7.27 (s, 3H, ArH), 7.44 (d, J = 4.4 Hz, 2H, ArH), 7.92 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = 27.5, 56.3, 82.3, 91.0, 102.0, 112.4, 112.8, 116.2, 123.8, 124.2, 127.3, 128.6, 132.1, 132.3, 154.3 ppm; HRMS (ESI) m/z: calcd. for C27H22N2O2 [M + H]+ : 407.1754 found 407.1780.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(5-methyl-1H-indole) (Figure 3B10): Isolated yield 72% as a brown solid; m.p. 128-130 oC; Rf = 0.53 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 2938, 2344 ; 1H NMR (600 MHz, CDCl3) d = 2.42 (s, 6H, CH3), 5.69 (s, 1H, CH), 7.01 (d, J = 8.1 Hz, 2H, ArH), 7.08 (s, 2H, ArH), 7.25 (t, J = 1.9 Hz, 3H, ArH), 7.27 (t, J = 4.9 Hz, 2H, ArH), 7.43 (d, J = 4.2 Hz, 2H, ArH), 7.55 (s, 2H, ArH), 7.88 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = 22.0, 27.4, 82.1, 91.4, 111.3, 116.1, 119.9, 123.3, 124.1, 124.5, 127.1, 128.0, 128.6, 129.1, 132.2, 135.5 ppm; HRMS (ESI) m/z: calcd. for C27H22N2 [M + H]+ : 375.1856 found 375.1860.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(5-methyl-1H-indole) (Figure 3B11): Isolated yield 92% as a pale brown semisolid; Rf = 0.49 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 2938, 2344; 1H NMR (600 MHz, CDCl3) d =2.42 (s, 6H, CH3), 5.69 (s, 1H, CH), 7.01 (dd, J = 1.7, 8.2 Hz, 2H, ArH), 7.06 (t, J = 2.5 Hz, 2H, ArH) 7.14 (s, 2H, ArH), 7.25 (d, J = 2.1 Hz, 2H, ArH), 7.26 (d, J = 1.4 Hz, 1H, ArH), 7.42 (d, J = 2.1 Hz, 1H, ArH), 7.43 (t, J = 3.2 Hz, 1H, ArH), 7.62 (d, J = 8.1 Hz, 2H, ArH), 7.85 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3) d = 21.8, 27.2, 81.8, 91.0, 111.2, 116.2, 119.5, 121.3, 122.0, 124.1, 124.4, 127.7, 128.2, 131.9, 131.9, 137.3.ppm; HRMS (ESI) m/z: calcd. for C27H22N2 [M + H]+ : 375.1856 found 375.1860.
3,3'-(3-phenylprop-2-yne-1,1-diyl)bis(5-nitro-1H-indole) (Figure 3B12): Isolated yield 90% as a pale brown semisolid; Rf = 0.39 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3481, 2352, 1469, 1385, 1391 886, 452; 1H NMR (600 MHz, DMSO-d6) d =5.38 (s, 1H, CH), 6.88 (d, J = 4.5 Hz, 3H, ArH), 7.00 (s, 2H, ArH), 7.02 (s, 1H, ArH), 7.03-7.05 (m, 2H, ArH), 7.12 (s, 1H, ArH), 7.59 (d, J = 9.0 Hz, 2H, ArH), 8.23 (s, 2H, ArH), 10.75 (s, 2H, ArNH) ppm; 13C NMR = 13 C NMR spectrum has not been recorded due to its insolubility in CDCl3 as well as DMSO-d6. HRMS (ESI) m/z: calcd. for C27H16N4 [M + H]+ : 437.1244 found 437.1255. 3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(2-methyl-1H-indole) (Figure 3B13): Isolated yield 92% as a brown coloured solid; m.p. 162- 164 oC; Rf = 0.51 ( EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3374, 3054, 2355, 1568, 1450, 737, 509, 437; 1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 2.98 (s, 6H, CH3), 5.80 (s, 1H, CH), 6.93 - 6.96 (m, 2H, ArH), 7.03 (t, J = 7.0 Hz, 2H, ArH), 7.28-7.31 (m, 4H, ArH), 7.43-7.45 (m, 2H, ArH), 7.60 (t, J = 8.2 Hz, 1H, ArH), 7.71 (d, J = 8.0 Hz, 2H, ArH), 9.92 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 13.0, 26.3, 82.3, 91.7, 110.6, 111.1, 119.5, 119.7, 121.3, 124.6, 128.0, 128.5, 128.6, 131.7, 132.0, 135.3.ppm;.HRMS (ESI) m/z: calcd. for C27H22N2 [M + H]+ : 375.1856 found 375.1865.
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(1-methyl-1H-indole) (Figure 3B14): Isolated yield 68% as a pale brown coloured solid; m.p. 88-90 oC; Rf = 0.51, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 2355, 1568, 1450, 737, 509, 437; ( 1H NMR (600 MHz, CDCl3): d = 3.73 (s, 6H, CH3), 5.74 (s, 1H, CH), 7.00 (s, 2H, ArH), 7.08 (t, J = 9.1 Hz, 2H, ArH), 7.22 (t, J = 9.5 Hz, 2H, ArH), 7.30 (d, J = 10.2 Hz, 5H, ArH), 7.44 (d, J = 4.32 Hz, 2H, ArH), 7.76 (d, J = 9.7 Hz, 2H, ArH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.2, 33.2, 82.0, 91.5, 109.8, 115.1, 119.3, 120.3, 122.0, 124.4, 127.2, 127.7, 128.1, 128.6, 132.2, 137.9 ppm;); HRMS (ESI) m/z: calcd. for C27H22N2 [M + H]+ : 375.1856 found 375.1865.
3,3'-(3-(4-chlorophenyl)prop-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B15): Isolated yield 65% as brown coloured solid; m.p. 178-180 oC; Rf = 0.38, (EtOAc/hexane, 1:4 v/v ; IR (neat): ?max cm-1 = 2359, 1655, 1549, 1419, 1326, 1180, 761, 562, 427.;1H NMR (600 MHz, CDCl3): d = 5.74 (s, 1H, CH), 7.09 (t, J = 8.9Hz, 2H, ArH), 7.14 (d, J = 2.9 Hz, 2H, ArH), 7.18-7.22 (m, 2H, ArH), 7.24 (d, J = 10.2 Hz, 2H, ArH), 7.37 (t, J = 9.9 Hz, 4H, ArH), 7.74 (d, J = 10.0 Hz, 2H, ArH), 8.00 (s, 2H, ArH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.1, 80.9, 91.8, 111.4, 116.0, 119.6, 119.9, 122.3, 122.7, 126.4, 128.5, 133.0, 136.8. ppm; HRMS (ESI) m/z: calcd. for C25H15Br2ClN2 [M + H]+ : 381.1153 found 381.1165.
3,3'-(3-(4-Chlorophenyl)prop-2-yne-1,1-diyl)bis(5-bromo-1H-indole) (Figure 3B16): Isolated yield 58% as brown coloured solid; m.p. 170-172 oC; Rf = 0.41, (EtOAc/hexane, 1:4 v/v ; IR (neat): ?max cm1 = 2359, 1655, 1549, 1419, 1326, 1180, 761, 562, 427.;1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 7.07 (t, J = 7.8 Hz, 2H, ArH), 7.22 (s, 1H, ArH), 7.28 (d, J = 2.8 Hz, 1H, ArH), 7.32 (d, J = 7.7 Hz, 2H, ArH), 7.47 (t, J = 7.5 Hz, 1H, ArH), 7.54-7.55 (m, 1H, ArH), 7.75 (d, J = 7.1 Hz, 1H, ArH), 7.84 (d, J = 8.2 Hz, 1H, ArH), 7.89 (t, J = 3.5 Hz, 1H, ArH), 8.49 (t, J = 6.06 Hz, 1H, ArH), 9.7 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 28.0, 81.7, 97.5, 111.0, 114.9, 119.2, 122.2, 123.5, 124.8, 125.4, 125.6, 126.6, 127.0, 127.1, 128.4, 128.5, 130.5, 133.6, 134.0, 138.5 ppm; HRMS (ESI) m/z: calcd. for C25H15Br2ClN2 [M + H]+ : 536.9363 found 536.9372.
3,3'-(3-(4-Chlorophenyl)prop-2-yne-1,1-diyl)bis(2-methyl-1H-indole) (Figure 3B17): Isolated yield 71% as brown coloured solid; m.p. 80-82 oC; Rf = 0.41, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 2938, 2344, 160, 447; 1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 2.32 (s, 6H, CH3), 5.88 (s, 1H, CH), 7.05-7.08 (m, 2H, ArH), 7.13- 7.16 (m, 2H, ArH), 7.32-7.37 (m, 4H, ArH), 7.43 (d, J = 1.3 Hz, 1 H, ArH), 7.45 (t, J = 2.6 Hz, 1H, ArH), 7.79 (d, J = 8.0 Hz, 2H, ArH), 9.01 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 12.3, 25.9, 80.5, 92.7, 110.1, 110.3, 118.7, 118.8, 120.4, 122.6, 127.8, 128.4, 131.5, 132.6, 133.3, 135.0.ppm; HRMS (ESI) m/z: calcd. for C27H21ClN2 [M + H]+ : 409.
3,3'-(3-(4-Fluorophenyl)prop-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B18): Isolated yield 81% as pale brown coloured solid; m.p. 58- 60 oC; Rf = 0.43, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3459, 2916, 2344, 1660, 1229;1H NMR (600 MHz, CDCl3): d = 5.73 (s, 1H, CH), 6.95 (t, J = 10.4 Hz, 2H, ArH), 7.09 (t, J = 8.9 Hz, 2H, ArH), 7.15 (d, J = 3.0 Hz, 2H, ArH), 7.19 (t, J = 9.5 Hz, 2H, ArH), 7.38 (t, J = 9.6 Hz, 4H, ArH), 7.74 (d, J = 9.5 Hz, 2H, ArH), 8.01 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.4, 81.2, 90.7, 111.7, 115.7, 115.9, 116.5, 117.1, 119.9, 120.1, 120.2, 122.6, 122.6, 123.0, 124.3, 126.8, 127.3, 128.5, 131.1, 133.9, 134.0, 137.2, 163.8.ppm; HRMS (ESI) m/z: calcd. for C25H17FN2 [M + H]+ : 365.1449 found 365.1455.
3,3'-(3-(4-Fluorophenyl)prop-2-yne-1,1-diyl)bis(6-bromo-1H-indole) (Figure 3B19): Isolated yield 92% as brown coloured solid; m.p. 142-144 oC; Rf = 0.39, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3307, 2225, 1620; 1H NMR (600 MHz, CDCl3): d = 5.64 (s, 1H, CH), 6.96 (t, J = 7.9 Hz, 2H, ArH), 7.11 (s, 2H, ArH), 7.17 (d, J = 12.3 Hz, 2H, ArH), 7.38 (t, J = 10.7 Hz, 2H, ArH), 7.52-7.55 (m, 4H, ArH), 8.02 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.3, 81.6, 89.8, 114.8, 155.8, 116.0, 116.3, 116.4, 120.0, 121.4, 123.4, 123.6, 125.5, 133.9, 134.0, 138.3, 163.97 ppm; HRMS (ESI) m/z: calcd. for C25H15Br2FN2 [M + H]+ : 520.9659 found 520.9668.
3,3'-(3-(4-fluorophenyl)prop-2-yne-1,1-diyl)bis(1H-indole-5- carbonitrile)) (Figure 3B20): Isolated yield 94% as brown coloured solid; m.p. 194-196 oC; Rf = 0.43, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3452, 3306, 2218, 1754, 1621, 624, 405; 1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 5.64 (s, 1H, CH), 6.93-6.97 (m, 2H, ArH), 7.29 (d, J = 1.7 Hz, 1H, ArH), 7.31-7.32 (m, 2H, ArH), 7.33 (s, 1H, ArH), 7.36-7.38 (m, 2H, ArH), 7.40 (s, 1H, ArH), 7.42 (s, 1H, ArH), 7.90 (s, 2H, ArH), 10.59 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 27.1, 81.9, 88.7, 102.2, 112.7, 115.5, 115.7, 115.9, 121.0, 124.8, 125.0, 125.2, 125.8, 133.5, 133.6, 138.9, 161.2 ppm; .HRMS (ESI) m/z: calcd. for C27H15FN4 [M + H]+ : 414.1275 found 414.1279.
3,3'-(3-(4-Fluorophenyl)prop-2-yne-1,1-diyl)bis(5-methoxy1H-indole)) (Figure 3B21): Isolated yield 62% as off white coloured semi solid Rf = 0.31, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1= 3316, 2935, 2361, 1580, 1477, 1164, 798, 436.;1H NMR (600 MHz, CDCl3): 3.78 (s, 6H, OCH3), 5.64 (s, 1H, CH), 6.87 (t, J = 12.3 Hz, 2H, ArH), 6.94-6.96 (m, 2H, ArH), 6.96-6.98 (m, 1H, ArH), 7.04 (s, 1H, ArH), 7.09 (s, 1H, ArH), 7.21 (s, 1H, ArH), 7.25-7.29 (m, 2H, ArH), 7.40 (t, J = 8.6 Hz, 1H, ArH), 7.48 (t, J = 8.6 Hz, 1H, ArH), 7.90 (s, 1H, ArNH), 7.95 (s, 1H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d 25.4, 56.3, 81.8, 90.6, 102.0, 108.0, 112.4, 112.7, 116.0, 123.8, 125.1, 127.7, 128.1, 131.2, 132.3, 133.9, 139.5, 154.3 ppm; HRMS (ESI) m/z: calcd. for C27H21FN2O2 [M + H]+ : 425.1660 found 425.1668.
3,3'-(3-(p-tolyl)prop-2-yne-1,1-diyl)bis(4-fluoro-1H-indole) (Figure 3B22): Isolated yield 80% as brown coloured solid; m.p.158-160 oC; Rf = 0.39 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1= 3500, 3425, 3302, 2919, 2360, 1653, 1557, 1182, 1105, 928, 763, 440.; 1H NMR (600 MHz, CDCl3): d = 2.31 (s, 3H, CH3), 6.78 (s, 1H, CH), 7.07 (t, J = 4.14 Hz, 6H, ArH), 7.09 (d, J = 2.5 Hz, 2H, ArH), 7.24 (t, J = 4.1 Hz, 2H, ArH), 7.33 (d, J = 9.8 Hz, 2H, ArH), 8.06 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 21.9, 28.1, 83.0, 91.7, 110.3, 118.8, 121.1, 121.5, 123.1, 123.6, 125.9, 127.1, 129.3, 132.0, 138.0, 138.6 ppm; HRMS (ESI) m/z: calcd. for C26H18F2N2 [M + H]+ : 397.1511 found 397.1525. 3,3'-(3-(p-tolyl)prop-2-yne-1,1-diyl)bis(5-methyl-1H-indole) (Figure 3B23): Isolated yield 70% as pale brown coloured solid; m.p. 82- 84 oC Rf = 0.40, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 =3374, 3054, 2355, 1568, 1450, 737, 509, 437;1H NMR (600 MHz, CDCl3): d = 2.22 (s, 3H, CH3), 2.30 (s, 6H, CH3), 5.55 (s, 1H, CH), 6.86 (dd, J = 1.6, 8.2 Hz, 2H, ArH), 6.97-7.00 (m, 4H, ArH), 7.16 (d, J = 8.3 Hz, 2H, ArH), 7.22 (d, J = 8.0 Hz, 2H, ArH), 7.42 (s, 2H, ArH), 8.93 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 21.4, 21.6, 27.0, 81.5, 90.7, 111.2, 115.3, 119.3, 121.0, 123.0, 123.3, 126.6, 128.0, 129.0, 131.5, 135.3, 137.6.ppm; HRMS (ESI) m/z: calcd. for C28H24N2 [M + H]+ : 388.1934 found 388.1945.
3,3'-(3-(2-Chlorophenyl)prop-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B24): Isolated yield 95% as a brown coloured viscous liquid Rf = 0.36, (EtOAc/hexane, 1:4 v/v); IR (neat):?max cm-1 =3286, 2360, 2217, 1615, 760, 544, 452.;1H NMR (600 MHz, CDCl3): d = 5.81 (s, 1H, CH), 7.09 (t, J = 7.3 Hz, 2H, ArH), 7.17-7.20 (m, 4H, ArH), 7.24 (d, J = 2.5 Hz, 2H, ArH), 7.35-7.38 (m, 3H, ArH), 7.45 (d, J = 9.4 Hz, 1H, ArH), 7.76 (d, J = 8.0 Hz, 2H, ArH), 7.98 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.3, 79.0, 96.3, 111.4, 115.8, 119.5, 119.9, 122.2, 123.0, 123.8, 126.4, 128.8, 129.2, 133.7, 135.9, 136.8 ppm; HRMS (ESI) m/z: calcd. for C25H17ClN2 [M + H]+ : 380.1080 found 380.1090.
3,3'-(3-(2-Chlorophenyl)prop-2-yne-1,1-diyl)bis(1H-indole-5- carbonitrile) (Figure 3B25): Isolated yield 95% as brown coloured solid ; m.p. 220-222 oC; Rf = 0.45, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 =3286, 2360, 2217, 1615, 1470, 1430, 1355, 880, 803, 760, 544, 452.; 1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 5.73 (s, 1H, CH), 7.15-7.21 (m, 2H, ArH), 7.24 (d, J = 8.7 Hz, 2H, ArH), 7.34 (d, J = 8.0 Hz, 1H, ArH), 7.39-7.41 (m, 5H, ArH), 7.67 (s, 2H, ArH), 7.94 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 26.1, 78.3, 94.1, 100.3, 111.9, 114.1, 119.9, 122.0, 123.1, 123.9, 124.5, 124.6, 125.6, 128.2, 128.3, 132.4, 134.5, 137.9 ppm; HRMS (ESI) m/z: calcd. for C27H15ClN4 [M + H]+ : 431.1058 found 431.1065.
3,3'-(3-(2-Chlorophenyl)prop-2-yne-1,1-diyl)bis(5-nitro-1H-indole) (Figure 3B26): Isolated yield 81% as brown coloured solid; m.p. 190-192 oC; Rf = 0.39, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3497, 2361, 1473, 1384, 1311 878, 441;1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 5.82 (s, 1H, CH), 7.15-7.20 (m, 2H, ArH), 7.32 (dd, J = 1.8, 8.0 Hz, 1H, ArH), 7.38 (dd, J = 2.5, 9.0 Hz, 2H, ArH), 7.42-7.45 (m, 3H, ArH), 7.65 (d, J = 2.3 Hz, 2H, ArH), 791 (td, J = 2.2, 4.7 Hz. 2H, ArH), 8.57 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 27.4, 94.6, 111.6, 111.8, 116.9, 117.0, 117.3, 123.1, 125.3, 126.4, 126.5, 129.1, 129.2, , 133.4, 136.0, 140.3, 141.3 ppm; HRMS (ESI) m/z: calcd. for C25H15ClN4O4 [M + H]+ : 471.0855 found 471.0865.
3,3'-(3-(2-Fluorophenyl)prop-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B27): Isolated yield 73% as a brown coloured viscous liquid; Rf = 0.50, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 =3459, 2916, 2344, 1660, 1229;1H NMR (600 MHz, CDCl3): d = 5.86 (s, 1H, CH), 7.10-7.17 (m, 5H, ArH), 7.24 (d, J = 2.6 Hz, 1H, ArH), 7.27 (s, 1H, ArH) 7.30 (t, J = 7.7 Hz, 1H, ArH), 7.32 (d, J = 2.5 Hz, 1H, ArH), 7.42 (dd, J = 2.6 , 8.2 Hz, 2H, ArH), 7.48 (t, J = 7.2 Hz, 1H, ArH), 7.82 (d, J = 7.9 Hz, 2H, ArH), 8.05 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.4, 96.3, 106.9, 111.4, 115.7, 115.8, 119.5, 119.8, 122.1, 123.0, 123.9, 126.4, 129.5, 133.7, 136.8, 163.9 ppm; HRMS (ESI) m/z: calcd. for C25H17FN2 [M + H]+ : 365.1449 found 365.1455.
3,3'-(3-(2-fluorophenyl)prop-2-yne-1,1-diyl)bis(6-fluoro-1H-indole) (Figure 3B28): Isolated yield 91% as brown viscous liquid; Rf = 0.34, (EtOAc/hexane, 1:4 v/v) IR (neat): ?max cm-1 =3459, 2916, 2344, 1660, 1229, 1575 ; 1H NMR (600 MHz, CDCl3): d = 5.70 (s, 1H, CH), 6.82-6.86 (m, 2H, ArH), 7.02-7.18 (m, 4H, ArH), 7.18 (d, J = 2.6 Hz, 2H, ArH), 7.26 (d, J = 6.2 Hz, 1H, ArH), 7.39 (t J = 9.3 Hz, 1H, ArH), 7.61-7.63 (m, 2H, ArH), 8.01 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.4, 95.7, 97.5, 97.7, 108.4, 108.5, 112.2, 112.3, 115.4, 115.6, 115.8, 120.5, 120.6, 122.9, 123.0, 124.0, 129.6, 129.7, 133.6, 136.7, 136.8, 159.4, 160.9, 162.2, 163.9. ppm; HRMS (ESI) m/z: calcd. for C25H15F3N2 [M + H]+ : 400.1187 found 400.1195.
3,3'-(3-(2-Fluorophenyl)prop-2-yne-1,1-diyl)bis(5-methyl-1H-indole) (Figure 3B29): Isolated yield 90% as dark brown coloured semiliquid; Rf = 0.41, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3459, 2916, 2344, 1660, 1229, 440; 1H NMR (600 MHz, CDCl3): d = 2.43 (s, 6H, CH3), 5.72 (s, 1H, CH), 7.01-7.07 (m, 4H, ArH), 7.14 (d, J = 6.2 Hz, 2H, ArH), 7.23 (d, J = 9.2 Hz ,1H, ArH), 7.27 (d, J = 9.1 Hz, 2H, ArH), 7.42 (t, J = 7.2 Hz, 1H, ArH), 7.57 (d, J = 6.12 Hz, 2H, ArH), 7.88 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 21.6, 27.3, 75.3, 96.5, 111.0, 112.6, 112.7, 115.3, 115.4, 115.5, 119.5, 123.1, 123.8, 123.9, 126.7, 128.7, 129.3, 129.4, 133.7, 135.2, 162.3, 163.9. ppm; HRMS (ESI) m/z: calcd. for C27H21FN2 [M + H]+ : 393.1762 found 393.1777.
3,3'-(3-(3-Methoxyphenyl)prop-2-yne-1,1-diyl)bis(1H-indole)(Figure 3B30): Isolated yield 72% as pale brown coloured solid; m.p 78-80 oC; Rf = 0.35, (EtOAc/hexane, 1:4 v/v) IR (neat): ?max cm-1= 3423, 2995, 1587, 1399, 470; 1H NMR (600 MHz, CDCl3): d = 3.76 (s, 3H, OCH3), 5.75 (s, 1H, CH), 6.82 (d, J = 10.2 Hz, 1H, ArH), 6.97 (s, 1H, ArH), 7.04 (d, J = 8.7 Hz, 1H, ArH), 7.07-7.10 (m, 2H, ArH), 7.15-7.16 (m, 2H, ArH), 7.17-7.20 (m, 3H, ArH) 7.36 (d, J = 8.16 Hz, 2H, ArH), 7.75 (d, J = 8.0 Hz, 2H, ArH), 7.98 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3): d = 27.1, 55.3, 81.9, 90.6, 111.3, 114.4, 116.2, 116.8, 119.7, 119.9, 119.9, 122.1, 122.6, 122.8, 124.5, 125.0, 126.4, 129.3, 136.8, 159.3 ppm; HRMS (ESI) m/z: calcd. for C26H20N2O [M + H]+ : 377.1648 found 377.1655.
3,3'-(3-(3-Methoxyphenyl)prop-2-yne-1,1-diyl)bis(6-bromo-1H-indole) (Figure 3B31): Isolated yield 66% as yellow brown coloured solid; m.p. 99-101 oC; Rf = 0.41 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1=3423, 2995, 1852, 1587, 1399, 1162, 988, 703, 569, 470; 1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 3.70 (s, 3H, OCH3), 5.56 (s, 1H, CH), 6.76 (td, J = 2.34, 4.4 Hz, 1H, ArH), 6.83 (t, J = 2.16 Hz, 1H, ArH), 6.90 (d, J = 7.6 Hz, 1H, ArH), 6.95-6.97 (m, 2H, ArH), 7.10-7.13 (m, 3H, ArH), 7.42 (dd, J = 10.2, 12.4 Hz, 2H, ArH), 7.66 (s, 2H, ArH), 7.67 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 34.4, 86.2, 96.4, 119.3, 119.9, 121.4, 123.5, 124.2, 125.5, 126.1, 126.6, 127.8, 128.6, 129.9, 131.0, 132.6, 133.1, 134.2, 136.3, 141.8, 142.7, 164.1 ppm; HRMS (ESI) m/z: calcd. for C26H18Br2N2O [M + H]+ : 532.9859 found 532.9868.
3,3'-(3-(3-Methoxyphenyl)prop-2-yne-1,1-diyl)bis(4-chloro-1H-indole) (Figure 3B32): Isolated yield 80% as a brown coloured semisolid; Rf = 0.35; (EtOAc/hexane, 1:4 v/v) ; IR (neat): ?max cm-1 =3449, 3289, 2981, 2827, 1637, 1502, 1020, 806, 631, 562, 479.; 1H NMR (600 MHz, CDCl3): d = 3.77 (s, 3H, OCH3), 5.61 (s, 1H, CH), 6.84 (d, J = 13.2 Hz, 1H, ArH), 6.92 (t, J = 14 Hz, 2H, ArH), 6.98 (d, J = 5.0 Hz, 1H, ArH), 7.05 (d, J = 9.2 Hz, 1H, ArH), 7.19 (t, J = 9.4 Hz, 1H, ArH), 7.24 (s, 2H, ArH), 7.27 (t, J = 5.3 Hz, 2H, ArH), 7.34 (d, J = 14.6 Hz, 2H, ArH), 8.03 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.6, 55.7, 82.7, 90.1, 105.0, 105.2, 110.9, 111.2, 112.3, 112.4, 115.0, 116.2, 116.3, 116.9, 124.7, 125.0, 126.9, 127.0, 129.7, 133.7, 156.9, 159.2, 159.7.ppm; HRMS (ESI) m/z: calcd. for C26H18Cl2N2O [M + H]+ : 445.0869 found 445.0877.
3,3'-(3-(Naphthalen-1-yl)prop-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B33): Isolated yield 88% as dark brown coloured solid; m.p. 108-110 oC; Rf = 0.41 (EtOAc/hexane, 1:4 v/v v); IR (neat): ?max cm-1 = 3012, 2389, 1512, 1229, 778.; 1H NMR (600 MHz, CDCl3): d = 5.92 (s, 1H, CH), 7.09-7.12 (m, 2H, ArH), 7.20 (t, J = 7.1 Hz, 2H, ArH), 7.23 (d, J = 2.5 Hz, 2H, ArH), 7.36-7.39 (m, 3H, ArH), 7.43-7.48 (m, 2H, ArH), 7.66 (d, J = 7.2 Hz, 1H, ArH), 7.76-7.83 (m, 4H, ArH), 8.01 (s, 2H, ArNH), 8.34 (d, J = 8.4 Hz, 1H, ArH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.7, 60.8, 80.1, 96.0, 111.4, 116.3, 119.6, 120.0, 121.7, 122.2, 122.8, 125.4, 126.3, 126.5, 126.6, 128.2, 130.4, 133.2, 133.6, 136.8.ppm; HRMS (ESI) m/z: calcd. for C29H20N2 [M + H]+ : 397.1699 found 397.1701.
3,3'-(3-(Naphthalen-1-yl)prop-2-yne-1,1-diyl)bis(1H-indole-5- carbonitrile) (Figure 3B34): Isolated yield 81% as brown coloured solid; m.p. 228-230 oC; Rf = 0.34, (EtOAc/hexane, 1:4 v/v; IR (neat): ?max cm-1 = 3301, 2231, 1614, 1110 ; 1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 5.82 (s, 1H, CH), 7.27-7.28 (m, 2H, ArH), 7.35 (t, J = 8.4 Hz, 1H, ArH), 7.41-7.42 (m, 2H, ArH), 7.43-7.44 (m, 4H, ArH), 7.56-7.59 (m, 3H, ArH), 7.73-7.77 (m, 2H, ArH), 7.97 (s, 2H, ArH), 8.17 (d, J = 3.9 Hz, 1H, ArH) ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 27.0, 81.3, 89.6, 114.3, 114.4, 115.5, 115.6, 116.0, 116.2, 119.6, 119.6, 121.0, 123.0, 123.2, 125.2, 128.4, 130.8, 130.9, 133.6, 133.6, 137.6. ppm; HRMS (ESI) m/z: calcd. for C31H18N4 [M + H]+ : 447.1604 found 447.1618.
3,3'-(3-(Naphthalen-1-yl)prop-2-yne-1,1-diyl)bis(5-methyl-1H-indole) (Figure 3B35): Isolated yield 89% as pale brown coloured powder; m.p. 126-128 oC, Rf = 0.37, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3425, 2350, 1642, 1070, 799; 1H NMR (600 MHz, CDCl3): d = 2.43 (s, 6H, CH3), 5.85 (s, 1H, CH), 7.04 (d, J = 8.3 Hz, 2H, ArH ), 7.17 (d, J = 2.6 Hz, 2H, ArH), 7.27 (d, J = 8.3 Hz, 2H, ArH), 7.38 (t, J = 7.3 Hz, 1H, ArH), 7.43-7.48 (m, 2H, ArH), 7.64 (t, J = 7.1 Hz, 3H, ArH), 7.76 (d, J = 8.0 Hz, 1H, ArH), 7.80 (d, J = 8.8 Hz, 1H, ArH), 7.92 (s, 2H, ArNH), 8.38 (d, J = 7.9 Hz, 1H, ArH) ppm; 13C NMR (150 MHz, CDCl3): d = 21.7, 27.4, 80.0, 96.2, 111.0, 115.8, 119.6, 121.9, 122.8, 123.0, 123.8, 125.3, 126.3, 126.6, 126.7, 128.1, 128.2, 128.7, 130.3, 133.3, 133.7, 135.2 ppm; HRMS (ESI) m/z: calcd. for C31H24N2 [M + H]+ : 425.2012 found 425.2022.
3,3'-(3-(Naphthalen-1-yl)prop-2-yne-1,1-diyl)bis(5-nitro-1H-indole) (Figure 3B36): Isolated yield 75% as brown coloured semisolid, Rf = 0.35, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3012, 2389, 1467, 1512, 1229, 778; 1H NMR (600 MHz, CDCl3 + DMSOd6): d = 5.92 (s, 1H, CH), 7.41-7.44 (m, 3H, ArH), 7.45-7.47 (m, 2H, ArH), 7.50 (d, J = 3.7 Hz, 2H, ArH), 7.75-7.78 (m, 3H, ArH), 7.89-7.94 (m, 4H, ArH), 7.98 (s, 1H, ArH), 8.64 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 29.6, 89.7, 11.8, 116.8, 117.2, 120.5, 125.3, 126.0, 126.3, 126.5, 127.7, 127.9, 128.4, 131.4, 132.6, 140.3, 141.0. ppm; HRMS (ESI) m/z: calcd. for C29H18N4O4 [M + H]+ : 487.1401 found 487.1415.
3,3'-(3-(Naphthalen-2-yl)prop-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B37): Isolated yield 88% as brown coloured solid; m.p 110-112 oC; Rf= 0.41, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3404, 2330, 2110, 1416, 1339, 737, 485; 1H NMR (600 MHz, CDCl3): d = 5.80 (s, 1H, CH), 7.10 (t, J = 7.08 Hz, 2H, ArH), 7.20-7.22 (m, 4H, ArH), 7.38 (d, J = 8.2 Hz, 2H, ArH), 7.45 (t, J = 4.6 Hz, 2H, ArH), 7.49 (dd, J = 1.8, 8.4 Hz, 1H, ArH), 7.72-7.75 (m, 2H, ArH), 7.78-7.80 (m, 3H, ArH), 7.95 (s, 1H, ArH), 8.00 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.2, 82.3, 91.2, 111.4, 116.3, 119.86, 120.0, 121.4, 122.3, 122.08, 126.4, 126.5, 126.6, 127.7, 127.8, 127.8, 129.0, 131.4, 132.6, 133.1, 136.8.ppm; HRMS (ESI) m/z: calcd. for C29H20N2 [M + H]+ : 397.1699 found 397.1701.
3,3'-(3-(Naphthalen-2-yl)prop-2-yne-1,1-diyl)bis(6-bromo-1H-indole) (Figure 3B38): Isolated yield 80% as brown coloured solid; m.p. 79-81 oC; Rf = 0.42, SiO2, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 = 3420, 3052, 1703, 1604, 1540, 1444, 799, 743, 581, 426.; 1H NMR (600 MHz, CDCl3): d = 5.71 (s, 1H,CH), 7.16-7.17 (m, 2H, ArH), 7.20 (td, J = 1.4, 2.7 Hz , 2H, ArH) 7.45-7.47 (m, 3H, ArH), 7.53 (t, J = 1.4 Hz, 2H, ArH), 7.59 (d, J = 8.5 Hz, 2H, ArH), 7.73- 7.76 (m, 2H, ArH), 7.78-7.79 (m, 1H, ArH), 7.93 (s, 1H, ArH), 8.02 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 27.1, 82.8, 90.3, 114.3, 116.0, 116.2, 120.9, 121.1, 123.0, 123.2, 125.2, 126.6, 127.7, 127.8, 127.9, 128.0, 128.8, 131.4, 132.8, 133.1, 137.6. ppm; HRMS (ESI) m/z: calcd. for C29H18Br2N2 [M + H]+ : 551.9837V found 551.9845.
3,3'-(3-Cyclopropylprop-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B39): Isolated yield 57% as brown coloured solid; m.p. 92-94 oC; Rf = 0.48 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1= 3435, 2216, 1720, 1580, 1469, 884, 756, 470.; 1H NMR (600 MHz, CDCl3): d = 0.65-0.67 (m, 2H, CH2), 0.69-0.71 (m, 2H, CH2), 1.25 - 1.29 (m, 1H, CH), 5.46 (s, 1H, CH), 7.04-7.07 (m, 4H, ArH), 7.14-7.17 (m, 2H, ArH), 7.33 (dt, J = 1.0, 8.1 Hz, 2H, ArH), 7.66 (dd, J = 1.0, 8.0 Hz, 2H, ArH), 7.90 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d 8.2, 26.4, 76.3, 84.9, 111.3, 116.8, 119.3, 119.9, 122.0, 122.6, 126.4, 136.9.; HRMS (ESI) m/z: calcd. for C22H18N2 [M + H]+ : 311.1543 found 311.1551.
3,3'-(3-Cyclopropylprop-2-yne-1,1-diyl)bis(5-bromo-1H-indole) (Figure 3B40): Isolated yield 40% as brown coloured solid; m.p. 92-94 oC; Rf = 0.38 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1= 3412, 2251, 1701, 1561, 1451, 862, 735, 464.; 1H NMR (600 MHz, CDCl3): d = 0.70-0.71 (m, 2H, CH2), 0.74-0.77 (m, 2H, CH2), 1.24-1.29 (m, 1H, CH), 5.32 (s, 1H, CH), 7.07 (d, J = 6.5 Hz, 2H, ArH), 7.21-7.24 (m, 4H, ArH), 7.77 (s, 2H, ArH), 8.01 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 0.4, 27.4, 82.8, 90.2, 114.6, 116.3, 116.6, 121.4, 123.3, 123.5, 123.9, 125.6, 128.4, 128.7, 132.1, 137.9.ppm; HRMS (ESI) m/z: calcd. for C22H16Br2N2 [M + H]+ : 466.9753 found 466.9761.
3,3'-(3-Cyclopropylprop-2-yne-1,1-diyl)bis(5-fluoro-1H-indole) (Figure 3B41): Isolated yield 57% as brown coloured solid; m.p 96-98 oC; Rf = 0.50 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1= 3302, 2938, 2830, 2164, 1629, 1019, 932, 601, 508, 436.; 1H NMR (600 MHz, CDCl3): d = 0.68-0.69 (m, 2H, CH2), 0.73-0.76 (m, 2H, CH2), 1.29-1.31 (m, 1H, CH), 5.33 (s, 1H, CH), 6.92 (td, J = 2.7, 9.06 Hz, 2H, ArH), 7.14 (d, J = 2.8 Hz, 2H, ArH), 7.23-7.24 (m, 2H, ArH), 7.27 (d, J = 2.7 Hz, 2H, ArH), 7.95 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 0.1, 8.5, 26.8, 75.6, 85.7, 105.0, 105.1, 110.7, 110.9, 112.1, 112.2, 116.9, 116.9, 124.4, 126.9, 126.9, 133.6, 157.1, 158.6 ppm; HRMS (ESI) m/z: calcd. for C22H16F2N2 [M + H]+ : 347.1354 found 347.1365.
3,3'-(3-Cyclopropylprop-2-yne-1,1-diyl)bis(5-methyl-1Hindole) (Figure 3B42): Isolated yield 69% as pale brown coloured solid; m.p. 138-140 oC; Rf = 0.49 (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1= 3393, 3018, 2866, 2364, 1671, 1528, 1467, 1090, 787, 593, 506, 422; 1H NMR (600 MHz, CDCl3): d = 0.67-0.69 (m, 2H, CH2), 0.71-0.73 (m, 2H, CH2), 0.87-0.90 (m, 1H, CH), 2.41 (s, 6H, CH3), 5.40 (s, 1H, CH), 6.98-7.01 (m, 4H, ArH), 7.22-7.23 (m, 2H, ArH), 7.47 (s, 2H, ArH), 7.81 (s, 2H, ArNH). ppm; 13C NMR (150 MHz, CDCl3): d = 0.2, 8.4, 21.9, 26.6, 76.6, 84.9, 111.1, 116.7, 119.8, 123.0, 123.9, 127.0, 128.8, 135.4 ppm; HRMS (ESI) m/z: calcd. for C24H22N2 [M + H]+ : 339.1856 found 339.1861.
3,3'-(3-Cyclopropylprop-2-yne-1,1-diyl)bis(5-nitro-1H-indole) (Figure 3B43): Isolated yield 49% as brown coloured solid; m.p. 100-102 oC; Rf = 0.51, (EtOAc/hexane, 1:4 v/v IR (neat): ?max cm-1 = 3397, 2344, 1467, 1326, 742; 1H NMR (600 MHz, CDCl3): d = 0.71-0.72 (m, 2H,CH2), 0.74-0.77 (m, 2H,CH2), 1.29-1.32 (m, 1H,CH), 5.33 (s, 1H, CH), 7.07 (d, J = 2.7 Hz, 2H, ArH), 7.21 (d, J = 8.7 Hz, 2H, ArH), 7.24-7.25 (m, 2H, ArH), 7.77 (s, 2H, ArH), 8.02 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 0.1, 8.5, 26.7, 75.5, 86.0, 113.0, 113.4, 116.4, 122.7, 123.9, 125.3, 128.2, 135.7 ppm; HRMS (ESI) m/z: calcd. for C22H16N4O2 [M + H]+ : 401.1244 found 401.1255.
3,3'-(Oct-2-yne-1,1-diyl)bis(1H-indole) (Figure 3B44): Isolated yield 71% as brown coloured solid; m.p. 75-77 oC; Rf = 0.38, (EtOAc/hexane, 1:4 v/v ; IR (neat): ?max cm-1= 3404, 2924, 1608, 1447, 1327, 1091, 799, 496; 1H NMR (600 MHz, CDCl3): d = 0.87 (t, J = 7.32 Hz, 3H, CH3), 1.26-131 (m, 2H, CH2), 1.37-1.41 (m, 2H, CH2), 1.52-1.54 (m, 2H, CH2), 2.23-2.25 (m, 2H, CH2), 5.49 (t, J = 2.3 Hz, 1H, ArH), 7.04-7.07 (m, 4H, ArH), 7.15-7.18 (m, 2H, ArH), 7.33-7.35 (m, 2H, ArH), 7.68-7.70 (m, 2H, ArH), 7.92 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3): d = 14.4, 19.3, 22.6, 26.7, 29.1, 31.5, 81.1, 82.2, 111.4, 117.4, 119.6, 120.2, 122.3, 122.8, 126.8, 137.0.ppm; HRMS (ESI) m/z: calcd. for C24H24N2 [M + H]+ : 327.1856 found 327.1875.
3,3'-(Oct-2-yne-1,1-diyl)bis(5-bromo-1H-indole) (Figure 3B45): Isolated yield 46% as brown coloured solid; m.p. 99-101 oC; Rf = 0.39, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1=3404, 2924, 1608, 1447, 1327, 1091, 799, 496.; 1H NMR (600 MHz, CDCl3): d = 0.87 (t, J = 8.7 Hz, 3H, CH3), 1.25-1.41 (m, 6H, CH2), 2.25 (t, J = 11.3 Hz, 2H,CH2), 5.37 (s, 1H, CH), 7.10 (d, J = 3.0 Hz, 2H, ArH), 7.23 (t, J = 6.6 Hz, 4H, ArH), 7.79 (s, 2H, ArH), 8.03 (s, 2H, ArH).ppm; 13C NMR (150 MHz, CDCl3): d = 14.5, 19.4, 22.7, 26.8, 29.1, 31.6, 80.4, 83.2, 113.1, 116.7, 122.9, 124.0, 125.4, 128.4, 135.8.ppm; HRMS (ESI) m/z: calcd. for C24H22Br2N2 [M + H]+ : 497.0223 found 497.0231.
3,3'-(Oct-2-yne-1,1-diyl)bis(6-bromo-1H-indole) (Figure 3B46): Isolated yield 75% as brown coloured solid; m.p. 210-212 oC; Rf = 0.41, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1=3404, 2924, 1608, 1447, 1327, 1091, 799, 496.;1H NMR (600 MHz, CDCl3): d = 0.87 (t, J = 7.2 Hz, 3H, CH3), 1.29-1.37 (m, 4H, CH2), 1.50-1.56 (m, 2H, CH2), 2.22 (td, J = 2.3, 7.1 Hz, 2H, CH2), 5.41 (s, 1H, CH), 7.04 (d, J = 3.0 Hz, 2H, ArH), 7.14 (dd, J = 1.7, 8.5 Hz, 2H, ArH), 7.48-7.49 (m, 4H, ArH), 7.95 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 14.3, 19.2, 22.6, 26.6, 29.0, 31.5, 80.5, 82.9, 114.5, 116.0, 117.3, 121.4, 123.0, 123.3, 125.5, 137.8 ppm; HRMS (ESI) m/z: calcd. for C24H22Br2N2 [M + H]+ : 499.2695 found 499.2695.
3,3'-(Oct-2-yne-1,1-diyl)bis(4-chloro-1H-indole) (Figure 3B47): Isolated yield 73% as pale brown coloured solid; m.p.72-74 oC; Rf = 0.42, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 =3448, 2933, 2367, 1626, 1421;1H NMR (600 MHz, CDCl3): d = 0.85 (t, J = 7.4 Hz, 3H, CH3), 1.28-1.32 (m, 2H, CH2), 1.34-1.39 (m, 2H, CH2), 1.50-1.54 (m, 2H, CH2), 2.22 (t, J = 7.1 Hz, 2H, CH2), 6.55 (s, 1H, ArH), 7.00 (d, J = 2.8 Hz, 2H, ArH), 7.04-7.06 (m, 4H, ArH), 7.21 (d, J = 9.2 Hz, 2H, ArH), 8.00 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3): d = 14.3, 19.3, 22.6, 27.3, 29.1, 31.4, 82.6, 82.9, 110.2, 119.4, 120.9, 122.8, 123.4, 124.6, 126.9, 138.5.ppm; HRMS (ESI) m/z: calcd. for C24H22Cl2N2 [M + H]+ : 409.1233 found 409.1333.
3,3'-(Oct-2-yne-1,1-diyl)bis(5-methyl-1H-indole) (Figure 3B48): Isolated yield 76% as brown coloured semisolid; Rf = 0.35 ,(EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 =3448, 2933, 2367, 1626; 1H NMR (600 MHz, CDCl3): d = 0.87 (t, J = 7.3 Hz, 3H, CH3), 1.30-1.33 (m, 2H, CH2), 1.37-1.40 (m, 2H, CH2), 1.52-1.55 (m, 2H, CH2), 2.23 (td, J = 2.5, 7.2 Hz ,2H, CH2), 2.40 (s, 6H, CH3), 5.44 (d, J = 2.8 Hz, 1H, CH), 6.99-7.02 (m, 4H, ArH), 7.23 (d, J = 8.22 Hz, 2H, ArH), 7.49 (s, 2H, ArH), 7.85 (s, 2H, ArNH) ppm; 13C NMR (150 MHz, CDCl3): d = 14.1, 19.1, 21.6, 22.6, 26.4, 28.9, 31.3, 81.2, 81.8, 110.9, 116.6, 119.6, 122.8, 123.7, 126.8, 128.5, 135.2.ppm; HRMS (ESI) m/z: calcd. for C26H28N2 [M + H]+ : 369.2325 found 369.2331.
5-Nitro-3-(1-(4-nitro-1H-indol-3-yl)oct-2-yn-1-yl)-1H-indole (Figure 3B49): Isolated yield 70% as brown coloured solid; m.p 78-80 oC; Rf = 0.41, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1=3404, 2924, 1646, 1447, 799; 1H NMR (600 MHz, CDCl3 + DMSO-d6): d = 0.47 (t, J = 8.3 Hz, 3H, CH3), 1.19-1.38 (m, 6H, CH2),1 73 (t, J = 9.8 Hz, 2H, CH2), 5.96 (t, J = 7.7 Hz, 1H, ArH), 7.78-7.88 (m, 2H, ArH), 7.90-7.93 (m, 2H, ArH), 8.46-8.50 (m, 2H, ArH), 9.01-9.04 (m, 2H, ArH), 11.4 (s, 2H, ArNH).ppm; 13C NMR (150 MHz, CDCl3 + DMSO-d6): d = 7.8, 26.1, 74.7, 85.7, 111.4, 116.5, 116.7, 117.6, 125.0, 125.8, 140.0, 140.5 ppm; HRMS (ESI) m/z: calcd. for C24H22N4O4 [M + H]+ : 860.3282 found 860.3290.
3,3'-(Oct-2-yne-1,1-diyl)bis(2-methyl-1H-indole) (Figure 3B50): Isolated yield 77% as brown coloured solid; m.p. 110-112 oC; Rf = 0.39, (EtOAc/hexane, 1:4 v/v); IR (neat): ?max cm-1 =3552, 3376, 3052, 2923, 2858, 1452, 746, 503, 437.; 1H NMR (600 MHz, CDCl3): d = 0.86 (t, J = 7.3 Hz, 3H, CH3), 1.27-1.31 (m, 2H, CH2), 1.32-1.37 (m, 2H, CH2), 1.52 - 1.55 (m, 2H, CH2), 2.22 (td, J = 2.5, 7.2 Hz ,2H, CH2), 2.36 (s, 6H, CH3), 5.56 (t, J =2.5 Hz, 1H, CH), 6.99 (t, J =7.1 Hz, 2H, ArH), 7.06 (t, J = 9.4 Hz, 2H, ArH), 7.22 (d, J = 9.8 Hz, 2H, ArH), 7.66 (s, 2H, ArNH), 7.70 (d, J = 8.0 Hz, 2H, ArH).ppm; 13C NMR (150 MHz, CDCl3): d = 12.5, 14.1, 19.2, 22.4, 25.4, 28.7, 31.4, 82.0, 110.2, 111.6, 119.2, 119.4, 120.9, 128.2, 131.1, 135.0. ppm; HRMS (ESI) m/z: calcd. for C26H28N2 [M + H]+ : 369.2325 found 369.2333.
Many modifications will be apparent to those skilled in the art without departing from the scope of the present invention as hereinbefore described with reference to the accompanying drawings.
Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.
As used herein, the singular forms "a", "an", "the" include plural referents unless the context clearly dictates otherwise. Further, the terms "like", "as such", "for example", "including" are meant to introduce examples which further clarify more general subject matter, and should be contemplated for the persons skilled in the art to understand the subject matter.
The reference in this specification to any prior art publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgement or admission or any form of suggestion that the prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavor to which this specification relates.
The foregoing descriptions of exemplary embodiments of the present disclosure have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the disclosure to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching. The exemplary embodiments were chosen and described in order to best explain the principles of the disclosure and its practical application, to thereby enable others skilled in the art to best utilize the disclosure and various embodiments with various modifications as are suited to the particular use contemplated.
, C , Claims:We Claim
1. A process (300) for the synthesis of BIPS and derivatives thereof, the process (300) comprising:
(i) stirring 9-10 wt% of solution of 3-phenylpropiolaldehydes in anhydrous Acetonitrile (ACN);
(ii) adding 15-20 wt% of indole and 0.4-0.5 wt% of catalyst to a stirred solution of step (i) to obtain a reaction mixture;
(iii) stirring the reaction mixture obtained at step (ii) at room temperature at 600-800 RPM for 20-35 minutes;
(iv) monitoring the reaction mixture through Thin Layer Chromatography (TLC);
(v) quenching the reaction mixture with 1-1.5 wt% of aqueous solution of sodium thiosulphate and extracting thereto;
(vi) drying the extracted contents and concentrating thereto under reduced pressure in the range of 760-800 mm Hg to yield crude product of BIPs and derivatives thereof and purifying thereto.
2. The process (300) as claimed in claim 1, wherein the process (300) is free of transition metals.
3. The process (300) as claimed in claim 1, wherein the catalyst is iodine (I2).
4. The process (300) as claimed in claim 1, wherein the process (300) is completed within 20 to 40 minutes.
5. The process (300) as claimed in claim 1, wherein the process (300) comprising purification of the crude product through silica gel column.
6. The process (300) as claimed in claim 1, wherein the process (300) is free of pyrophoric conditions at low temperature.
Dated: 6th of November, 2024 Signature

Neha Goyal (IN/PA-4398)
(Agent of the Applicant)

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