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. 2026 Jan 30;11(6):10181–10190. doi: 10.1021/acsomega.5c11174

Bronsted and Lewis Acid-Catalyzed Diverse Functionalization of Indenoquinoxaline-11-Propargyl Alcohols: Synthesis of 4‑Indeno-quinoxalinylidene-2,3-diarylcyclobutenone, 1,2-Dimethoxy-2-Aryl-ethylideneindenoquinoxaline, and 2‑Methoxy-1-phenyldiaza-benzocyclopentafluorenes

Ammundi Jayavel Chirranjeevi Padmashrija †, Raman Kavitha Preethi †, Sathananthan Kannadasan †,*, Ponnusamy Shanmugam ‡,*
PMCID: PMC12917862  PMID: 41726752

Abstract

An efficient unprecedented synthesis of indenoquinoxaline-appended cyclobutenone derivatives has been developed from the reaction of indenoquinoxaline-11-propargyl alcohols using I2/BF3. OEt2 as a reagent system. On the other hand, the reaction using the combination of TMOF/p-TSA and I2/ TMOF/p-TSA as the reagent system afforded 1,2-dimethoxy-2-arylethylidene indenoquinoxaline and 2-methoxyphenyl diazabenzo-cyclopentafluorene, respectively. A plausible reaction mechanism is provided for the formation of all the products. All the compounds are characterized by spectroscopic data including single-crystal X-ray diffraction analysis.

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Introduction

Quinoxalines are one of the important heterocycle compounds possessing a wide range of biological applications including antimicrobial, antibacterial, antitubercular, antiviral, antifungal, antiprotozoan, antiamoebic, antiparasitic, antiglutamic, and anticancer properties. , For instance, Ampalex I is a drug used to treat Alzheimer disease (Figure ).

1.

1

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Some bioactive and functional materials I–VI with quinoxalines and indenoquinoxaline as core structures.

For example, indenoquinoxalinone derivative II showed acid corrosion inhibition property. In addition, indenoquinoxalinone derivatives are noteworthy scaffolds exhibiting broad spectrum of applications in material sciences, agrochemicals, and pharmaceuticals. In particular, compounds III–VI showed anticancer, α-glucosidase inhibition, antioxidant activity, and photonic sensors properties, respectively (Figure ). − In organic synthesis, indenquinoxalinones are widely employed as a synthon in multicomponent reactions (MCR) and in multistep synthesis.

Substituted propargylic alcohols are bifunctional frameworks showing versatility by generating nucleophilic and electrophilic centers, depending upon the reaction conditions, leading to the synthesis of diverse molecular architectures. − To exemplify, the formation of iodo-substituted derivatives via tandem cyclization involves iodine as an electrophile. Due to synthetic significance, we have been interested to explore the novel synthetic utility of the indenoquinoxaline-appended propargyl alcohols and demonstrated the synthesis of indenoquinoxalinone-5­(furano, pyrano, and oxepino)- spiro ethers and angularly fused diazabenzocyclopentafluorene via ring-closing enyne metathesis and iodocyclization as key reactions, respectively.

The synthesis of strained cyclobutene with ring strain energy of 26.7 kcal mol–1 is a challenging task in organic synthesis. Recently, we have reported the synthesis of highly strained substituted cyclopropane ring systems from 7-aza –2-indalone and diazo compounds.

Cyclobutenones hold a great importance due to their widespread photophysical and biological applications, , of which SQ VII is used in chromogenic and fluorogenic detection of sulfur mustard (SM) simulant, alterbrassicene A VIII, which prevents the progression of calcific aortic valve disease, cyclooxygenase-2 inhibitors (COX-2 inhibitor) IX is a nonsteroidal anti-inflammatory drug, and armillol X is a cyclobutanol-based natural product possessing antifungal activity (Figure ). −

2.

2

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Some compounds VII-X with cyclobutenone moieties attributing to photophysical and biological activities.

Due to ring strain, cyclobutenone is less stable and hence readily undergoes ring expansion; , however, stable substituted cyclobutenones were synthesized by uncommon reactions such as [2 + 2] cycloaddition between alkynes and ketenes, catalytic cyclization reactions of alkenes and alkynes, and cyclization of carbene and alkynes. In addition, difluorenyl cyclobutene was synthesized via dimerization and post ring-cyclization reaction. ,

In continuation of our current interest in exploring propargyl alcohol-appended indenoquinoxaline 2 as a synthon for the preparation of novel heterocyclic frameworks, recently we reported the reaction of propargyl alcohol-appended indenoquinoxaline 2 with Bronsted acid using I 2/p-TSA afforded angularly fused iodo-substituted ring system 7. In contrast, in the present study, the reaction of compound 2 under Lewis acid condition using I2/BF3. OEt2 as a reagent system yielded the unusual cyclobutenone-fused indenoquinoxaline 3 and such transformation is unknown in the literature. We have further explored the reaction, using trimethyl orthoformate (TMOF) − in the presence of Bronsted acid, and noticed that the TMOF acted as a methoxide nucleophile to provide 1,2-dialkoxy derivatives (Scheme ). The details of the preliminary results are presented in this manuscript.

1. Previous and Present Work.

1

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Results and Discussion

The starting materials, namely, propargyl alcohol-appended indenoquinoxaline 2a–p were synthesized by following a reported procedure (Figure ).

3.

3

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Synthesis of propargyl alcohol-appended indenoquinoxaline 2a–p substrates.

Then, the reaction of indenoquinoxaline propargyl alcohol 2a in DCE followed by the addition of BF3. OEt2 (1.0 equiv) and iodine (1.2 equiv) taken in a sealed tube was heated at 85 °C for 12 h, which furnished an unusual product, namely, 4-indenoquinoxalinylidene 2,3-diarylcyclobutenone 3a albeit in 15% yield (Scheme ), as confirmed from spectroscopic characterization and single-crystal X-ray diffraction (XRD) data (Figure ).

2. Preliminary Synthesis of Cyclobutenone Derivative 3a .

2

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4.

4

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ORTEP diagram of compound 3a (CCDC-2469004).

To optimize the reaction condition, initially a reaction of compound 2a was treated with BF3. OEt2 (0.5 equiv) and iodine (1.2 equiv) in DCM at 0 °C for 12 h and the reaction did not proceed (Table , entry 1). Increasing the mole equivalents of BF3. OEt2 (1.0 equiv) at rt and under reflux conditions, no significant change in the reaction was observed (Table , entries 2 and 3). While, when the temperature was raised to 95 °C and the reaction was carried out in a sealed tube using DCE as the solvent, the desired product 3a was obtained in slightly increased yield to 25% (Table , entry 4). Extending reaction time to 12 h yielded 28% of product 3a (Table , entry 5). When the reaction was carried out at 110 °C, decomposition occurred (Table , entry 6). On analyzing the structure of the product 3a and reaction conditions, the low yield of the product is probably due to the presence of two aryl groups in the product, which implies that the product would have been formed by cleavage, followed by cyclization of the starting material along with partial decomposition. It should be noted that the reaction occurred only in a sealed tube using DCE at 95 °C, and further increase in temperature resulted in decomposition. It has been noticed that along with Lewis acid, when iodine was added in the reaction, no iodinated product was observed. On the other hand, a reaction without the addition of iodine, to our surprise, did not proceed. This validates the crucial role of iodine as a catalyst or a promoter in the progress of the reaction (Table , entry 7)

1. Optimization of Synthesis of Indeoquinoxaline-Appended Cyclobutenone 3a .

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entry lewis acid (equiv) solvent temperature (°C) time (h) yield of 3a (%)
1 BF3. OEt2 (0.5) DCM 0 12 ,
2 BF3. OEt2 (1.0) DCM RT 12 ,
3 BF3. OEt2 (1.0) DCM 40 12 ,
4 BF3. OEt2 (1.0) DCE 95 06 25
5 BF3. OEt2 (1.0) DCE 95 12 28,
6 BF3. OEt2 (1.0) DCE 110 12 ,
7 BF3. OEt2 (1.0) DCE 95 12 ,,
8 TFA (1.0) DCE 95 06 ,
9 InCl3 (1.0) DCE 95 06 ,
10 FeCl3 (1.0) DCE 95 06 ,
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a

Reaction did not proceed.

b

Reaction carried out in the RB flask.

c

Reaction carried out in a sealed tube.

d

Optimized condition.

e

Decomposed.

f

Without iodine.

g

Resulted with iodocyclized product, 7a, however in lesser yield (Traces) compared to p-TSA catalyst.

Subsequently, to evaluate the role of Lewis acid BF3. OEt2, reactions with other Lewis and Bronsted acids such as trifluoroacetic acid, indium chloride, and ferric chloride were performed and all the reactions were failed to furnish the expected product 3a, however, under these conditions, only the iodocyclization product 7 was formed (Table , entries 8, 9, and 10). Thus, entry 5 of Table was chosen as the optimized reaction condition for the synthesis of 3a. Although we were unable to improve the yield with the attempts shown with various reaction parameters in Table , we proceeded to synthesize derivatives 3 due to structural significance and mechanistic interest.

Thus, with the optimized condition in hand, the scope, limitation, and diversity of the reaction were explored. Thus, among the indenoquinoxaline propargylic alcohol substrates 2a–2p, the formation of cyclobutenone derivatives 3a–3e was observed only from substrates 2a–2c, 2i, and 2j in low yields (Scheme ). Further, the compound 3d was crystallized and the structural evidence with ORTEP diagram obtained from SC-XRD data is provided in Figure .

3. Synthesized Cyclobutenone Derivatives 3a–3e .

3

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5.

5

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ORTEP diagram of compound 3d (CCDC-2373553).

To our dismay, attempts to extend the scope of the cyclobutenones were not possible as it ended up with either the decomposition of starting materials or with the formation of corresponding a trace amount of angularly fused iodocyclized products 7 (Table ). This might be due to the presence of substituents on the starting material causing destabilization of the highly strained cyclobutenone ring structure and/or the electronic effect preventing the cleavage and recombination to form the expected products during the course of the reaction.

2. Substrate Scope for the Formation of Cyclobutenone Product 3 .

entry
 substrate
 product(s) (%)
    3 7
1 2a 3a (28)
2 2b 3c (35)
3 2c 3e (37)
4 2d 7d (12)
5 2e 7e (8)
6 2f
7 2g
8 2h
9 2i 3b (27)
10 2j 3d (38)
11 2k
12 2l
13 2m 7m (10)
14 2n 7n (9)
15 2o 7o (11)
16 2p
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a

Product not formed.

b

Decomposition of the reaction mixture.

To arrive at a plausible reaction mechanism, a series of control experiments were carried out. The reactions shown in Table , entries 1 and 2 indicate that the reaction does not proceed when performed under open air conditions and both reactions performed at RT and 85 °C. Also, reactions shown in entries 3, 4, 5, and 6 imply under sealed tube condition, parameters such as temperature, BF3. OEt2, and I2 play a very crucial role for the reaction to occur. When the alcohol group is protected, the desired product is not formed (Table , entry 7). Thus, from Table , with all the control experiments, it is clearly evident that the reaction occurred only in a sealed tube at 95 °C and the reaction occurs through decomposition and recombination of the starting material.

3. Control Experiments for the Formation of 3 .

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entry substrate conditions product(s) (%)
3a 7a
1 2a BF3. OEt2, I2, RT, open RB
2 2a BF3. OEt2, I2, RT, 85 °C (reflux), open RB
3 2a BF3. OEt2, I2, 80 °C, sealed tube
4 2a BF3. OEt2, I2, 85 °C, sealed tube 15 -
5 2a without BF3. OEt2, with I2, 95 °C, sealed tube - 10
6 2a without I2, with BF3. OEt2, 95 °C, sealed tube
7 2a′ BF3.OEt2, I2, 95 °C, sealed tube
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a

No reaction, SM recovered.

b

Decomposed.

Based on control experiment results, a plausible mechanism for the formation of cyclobutenone product 3 is proposed in Scheme . , Initially, it is believed that in the presence of Lewis acid BF3. OEt2, the starting material 2 turns to a propargyl cation A intermediate which is in resonance as an allenyl cation B intermediate. Subsequent addition of water to allenyl cation B provides allenyl alcohol intermediate C which has not been isolated. On the other hand, it is believed that in the presence of iodine molecule, the propargyl alcohol 2 produces alkynyl iodide D, which upon thermal decomposition forms a ketene intermediate E. As an analogy, the formation of alkynyl iodide from disubstituted alkyne is reported. Subsequent [2 + 2]-cycloaddition of hydroxy allene intermediate C and ketene D provides another cyclobutenone alcohol intermediate F which upon elimination of a water molecule gives the observed product 3.

4. A Plausible Mechanism for the Formation Cyclobutenone Product 3 .

4

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Also, if the allenyl carbocation C is attacked by the iodide ion, cyclic iodinium ion intermediate (D′) would be formed via iodo allene intermediate (C′). Further, the nucleophilic attack by the intramolecular N-nucleophile will lead to the formation of the undesired product 7.

After limited success of I2/ BF3. OEt2-catalyzed synthesis of cyclobutenone derivatives discussed above prompted us to further explore the synthetic transformation of indenoquinoxaline-appended propargyl alcohol to functionalize the corresponding possible methoxy-substituted cyclobutenone. Thus, the reaction was repeated with indenoquinoxaline appended to propargyl alcohol 2 in the presence of TMOF and BF3. OEt2 as a catalyst. However, an initial investigation with BF3. OEt2 did not yield the desired methoxy-substituted cyclobutenone product. Hence, a change of the acid catalyst from Lewis to Bronsted acid such as p-TSA provided an unusual 1,2-dimethoxy-2-phenylethylidene-fused indenoquinoxaline 4a. The details of the study are discussed as follows.

Thus, the initial reaction of indenoquinoxaline-appended propargyl alcohol in the presence of TMOF and p-TSA resulted in the formation of an unusual 1,2-dimethoxy-2-phenylethylidene-fused indenoquinoxaline 4a, along with most common etherification product 5a in 25 and 42% yields, respectively (Scheme ). The structure of the products was confirmed by spectroscopic characterization. It should be noted that the one-pot formation of the unusual 1,2-dimethoxy-2-phenylethylidene-fused indenoquinoxaline 4a is rarely known in the literature.

5. Synthesis of 1,2-Dimethoxy-2-phenylethylidene Indenoquinoxaline 4a and 11-Methoxyindenoquinoxaline 5a .

5

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To optimize yield of the products by changing the reaction parameters such as the solvent, temperature, time, and reagents were considered (Table ). When DCM was used as a solvent under reflux for 12 h, the reaction did not proceed (Table , entry 1). Gradual increase in yield of the products was observed at different reaction temperatures, i.e., 50, 80, and 95 °C (Table , entries 2–4). Moreover, a further increase in the temperature led to decomposition of the reaction. Especially, to our dismay, when an attempt made to use methanol in place of TMOF, profound transformation was not observed (Table , entry 5). There was no reaction observed when a Lewis acid (BF3. OEt2) was used (Table , entry 6). Also, in the absence of acid reagents, reactions only with TMOF were attempted and the desired product was not observed (Table , entry 7). Thus, the reaction carried out in the presence of BF3. OEt2 and TMOF at 95 °C provided the desired products 4a and 5a in good yields of 35% and 47% and hence chosen as the optimized reaction condition (Table , entry 4). Consequently, utilizing the optimized procedure and to demonstrate the scope and limitations, derivatives 4a–4d and 5a–5d were synthesized from substrate 2, as shown in Scheme .

4. Optimization for the Formation of Compounds 4a and 5a .

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entry solvent reagent acid temp. (°C) time (h) products yield (%)
4a 5a
1 DCM HC(OCH3)3 p-TSA 40 12
2 DCE HC(OCH3)3 p-TSA 50 12
3 DCE HC(OCH3)3 p-TSA 80 06 20 40
4 DCE HC(OCH3)3 p-TSA 95 01 35 47
5 DCE CH3OH p-TSA 95 12
6 DCE HC(OCH3)3 BF3. OEt2 95 12
7 DCE HC(OCH3)3 - 95 12
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a

Reaction did not proceed.

b

Optimized condition.

6. Synthesis of 1,2-Dimethoxy-indenoquinoxalines 4a–4d and 11-Methoxy-indenoquinoxalines 5a–5d .

6

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The SC-XRD analysis for the representative compounds 4b and 5c confirms the assigned structure (Figure ).

6.

6

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ORTEP diagram of compounds 4b (CCDC 2496089) and 5c (CCDC 2469000).

A plausible mechanism for the formation of 1,2-dimethoxy substitution product 4 and etherification of alcohol 5 is shown in Scheme . The first step involves the generation of the allenyl B/alkynyl A carbocation via resonance. Subsequently, when the alkynyl carbocation A is attacked by methoxy nucleophile, it delivers methoxy-substituted ether product 5. On the other hand, in the case of allenyl carbocation B, it is attacked by the methoxy nucleophile leading to the formation of methoxy allene intermediate I which on addition of water followed by nucleophilic attack of another methoxy group, consequently, results in the formation of 1,2-dimethoxy-substituted product 4 (Scheme ). ,

7. Plausible Mechanism for the Formation of Compounds 4 and 5 .

7

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To further explore and to evaluate the competent role of the 1:1 combination of iodine and TMOF in the reaction, we further explored the reaction using the combination of these reagents in the presence of p-TSA, as shown in Scheme . Remarkably when the substrate 2a (1.0 equiv) was treated with TMOF (1.0 equiv), in the presence of iodine (1.0 equiv) and p-TSA (0.5 equiv), in DCE for 3 h, along with 1,2-dimethoxy product 4a, 2-methoxy-1-phenyldiazabenzo-cyclopentafluorene 6a was formed in 33% and 40% yields, respectively (Scheme ). The newly formed methoxycyclized product 6a was structurally similar to that of iodocyclized product 7.

8. Synthesis of 1,2-Dimethoxy-2-Phenylethylidene Indenoquinoxaline 4a and 2-Methoxy-1-phenyldiazabenzo Cyclopentafluorene 6a .

8

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The structures of compounds 4a and 6a were confirmed through spectroscopic data including Fourier transform infrared (FTIR), 1H NMR, 13C NMR, DEPT-135 NMR, and HRMS. Also, structure of compound 6a was evidenced with SC-XRD data and ORTEP diagram provided in Figure .

7.

7

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ORTEP diagram of compounds 6a (CCDC 2469002).

Similarly, in relevance with previously discussed mechanisms, it is believed that the in situ-generated allenyl carbocation B intermediate will be attacked by iodide nucleophile, leading to the formation of iodo-allene intermediate G, which subsequently forms a cyclic iodonium ion intermediate H. At this stage, this cyclic iodonium ring could be opened up by either intramolecular nitrogen nucleophile furnishing iodocyclized product 7 or it can be attacked by methoxy nucleophile of TMOF, ensuing with the methoxy-cyclized product 6a (Scheme ).

9. Plausible Mechanism for the Synthesis of 2-Methoxy-1-henyldiazabenzocyclopentafluorene 6a.

9

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Conclusion

In conclusion, three unique efficient synthetic transformations of propargyl alcohol-appended indenoquinoxaline were developed. First, the anomalous synthesis of highly strained and substituted cyclobutenone ring systems were reported using iodine/BF3. OEt2 and second a one-pot protocol for the synthesis of 1,2-dimethoxy-substituted products in the presence of TMOF and p-TSA, along with usual ether products were established. Finally, the reaction in the presence of TMOF-iodine-p-TSA furnished methoxy cyclized product. Plausible reaction mechanisms and characterization of the products were also established.

Experimental Section

Materials and Methods

All of the reactions were carried out in an oven-dried glassware. The progress of the reactions was monitored by thin-layer chromatography (TLC) using Merck precoated TLC plates (Merck 60 F254). Purification of the products was accomplished by column chromatography packed with silica gel (100–200 mesh). NMR spectra were recorded on a Bruker-400 MHz NMR spectrometer (400 MHz for 1H NMR and 125 MHz for 13C NMR) with CDCl3 as the solvent and TMS as the internal reference. Integrals are in accordance with assignments, and coupling constants are reported in Hertz (Hz). All 13C spectra reported are proton-decoupled. Multiplicity is indicated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublets), dt (doublet triplet), td (triplet of doublets), and br s (broad singlet). FTIR spectra were recorded on a PerkinElmer RX-IFT-IR spectrometer, and absorbance values are reported in units of cm–1. ESI HRMS was performed on a Waters­(R) Micromass (R) Q-TOF Micromass spectrometer. Yields refer to quantities obtained after chromatography.

General Procedure for the Synthesis of 4-Indenoquinoxalinylidene-2,3-diarylcyclobutenone (3a–3e)

In an oven-dried sealed tube, 100 mg of the propargylic alcohol starting material 2 was taken and dissolved in 3 mL of 1,2-DCE. To the solution was added boron trifluoride etherate (1.0 equiv) and stirred at room temperature; soon after the addition, the solution changed from turbid white to a yellowish green suspension. Then, 1.2 equiv of iodine was added at room temperature, immediately the color will be changed to reddish brown. Then, the temperature was raised to 95 °C slowly. Note that addition of iodine should not be done at elevated temperatures, which may lead to the formation of undesired iodo cyclized product, however in low yields. Thus, the reaction is monitored by every 30 min with the TLC. After 12 h, the reaction was completed and the sealed tube with the reaction mixture is cooled to room temperature. Then, it is worked up with ethyl acetate and water and the organic layer is extracted. The organic layer is again washed with brine solution. Then, the organic layer is separated and concentrated. The crude obtained after workup was made into slurry and loaded into the silica gel column chromatography for purification. Then, the pure bright yellow product which is nonpolar was isolated with 3% EtOAc/Hexane mixture.

General Procedure for the Synthesis of 1,2-Dimethoxy-2-arylethylidene indenoquinoxaline (4a–4d) and 11-Methoxy-11-(arylethynyl)-11H-indeno­[1,2-b]­quinoxaline (5a–5b)

In an oven-dried sealed tube, 100 mg of starting material 2 was dissolved in 3 mL of 1,2-DCE. To this turbid solution, trimethyl orthoformate (1.0 equiv) was added at room temperature and kept stirring; immediately, the color changed to mild yellow and then to deep yellow. At this stage, p-TSA was added and the temperature was raised from room temperature to 95 °C. The color deepens and when the temperature is reached between 85 and 95 °C, it turns into brown colored solution. Then, the reaction is allowed to proceed for 1 h. The completion of the reaction was monitored by TLC. Once the reaction is completed, the sealed tube containing the reaction mixture is cooled to room temperature. Later, the reaction mixture is worked up with ethyl acetate and water. The organic layer is then separated and washed with brine solution. The concentrated crude product is purified using silica gel column chromatography. The compound 4 is isolated with 2% with EA/hexane, and compound 5 can be isolated with 5% EtOAc/Hex.

General Procedure for the Synthesis of 2-Methoxy-1-phenyldiazabenzocyclopentafluorene (6a)

In an oven-dried sealed tube, 100 mg of starting material 2 was dissolved in 3 mL of 1,2-DCE. To this turbid solution was added trimethyl orthoformate (1.0 equiv) at room temperature and kept it for stirring, immediately the color changes to mild yellow and then to deep yellow. At this stage, p-TSA was added and the temperature was raised from room temperature to 95 °C. The color deepens and when the temperature is reached between 85 and 95 °C, it turns into brown colored solution. Once the color change was observed, then iodine (1.0 equiv) was added into the reaction mixture. The completion of the reaction was monitored continuously with TLC. Thus, the reaction was found to be completed in 3 h. The reaction mixture was cooled to room temperature, sodium thiosulfate was added to it, and the mixture was kept stirring, to quench the coloration of solvents due to the presence of excess unreacted iodine. Then, the reaction mixture is worked up with ethyl acetate and water. The combined organic layer was concentrated, and the crude is purified using silica gel column chromatography. The desired products 4a and 6a were isolated with 2% and 8% EtOAc/hexane mixture, respectively.

(E)-4-(11H-indeno­[1,2-b]­quinoxalin-11-ylidene)-2,3-diphenylcyclobut-2-en-1-one (3a)

Nature: bright yellow solid; yield: 28%; R f (8% EtOAc-hexane): 0.80; FTIR (KBr) υmax: 2907, 1761, 1613, 1450, 1342, 1255, 1025, 753, 507 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.97 (d, J = 7.9 Hz, 1H), 8.19 (d, J = 7.4 Hz, 1H), 8.04 (d, J = 8.1 Hz, 1H), 7.82 (dd, J = 8.2, 1.4 Hz, 2H), 7.62–7.65 (m, 1H), 7.58 (s, 1H), 7.56 (d, J = 1.3 Hz, 1H), 7.55–7.50 (m, 4H), 7.47–7.41 (m, 2H), 7.37–7.28 (m, 3H), 6.93 (dd, J = 8.3, 1.0 Hz, 1H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 184.9, 177.3, 161.9, 153.2, 152.7, 151.5, 139.9, 139.8, 139.3, 134.9, 130.5, 130.2, 128.5, 128.2, 128.1, 128.0, 127.9, 127.9, 127.3, 127.1, 126.9, 126.2, 126.0, 120.9 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 130.5, 030.2, 128.5, 128.2, 127.9, 127.3, 127.1, 126.9, 126.2, 126.0, 120.9 ppm.; HRMS (ESI): calcd for C31H18N2O (M + H) m/z = 435.1497; found = 435.1499.

(E)-4-(7,8-Dichloro-11H-indeno­[1,2-b]­quinoxalin-11-ylidene)-2,3-diphenylcyclobut-2-en-1-one (3b)

Nature: bright yellow solid; yield: 27%; R f (8% EtOAc-hexane): 0.82; FTIR (KBr) υmax: 2921, 2851, 1766, 1602, 1462, 1347, 1179, 1016, 518 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.93 (d, J = 7.9 Hz, 1H), 8.06 (t, J = 3.7 Hz, 1H), 7.82 (d, J = 8.3 Hz, 2H), 7.69–7.62 (m, 1H), 7.61–7.51 (m, 4H), 7.51–7.40 (m, 4H), 7.39–7.28 (m, 2H), 6.96 (s, 1H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 185.2, 141.3, 134.9, 134.0, 132.3, 132.1, 131.2, 130.1, 129.0, 129.9, 129.8, 129.3, 129.2, 129.2, 128.6, 128.4, 127.4, 122.0.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 134.4, 132.3, 131.4, 130.0, 129.9, 129.3, 128.6, 128.5, 127.4 ppm.; HRMS (ESI): calcd for C31H16Cl2N2O (M) m/z = 502.0640; found = 502.0642.

(E)-4-(11H-Indeno­[1,2-b]­quinoxalin-11-ylidene)-2,3-di-p-tolylcyclobut-2-en-1-one (3c)

Nature: bright yellow solid; yield: 35%; R f (8% EtOAc-hexane): 0.79; FTIR (KBr) υmax: 2923, 1753, 1604, 1455, 1264, 1013, 745, 518, 447 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.93 (d, J = 7.9 Hz, 1H), 8.09 (d, J = 7.6 Hz, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.74 (d, J = 8.1 Hz, 2H), 7.52 (t, J = 7.5 Hz, 2H), 7.45–7.35 (m, 4H), 7.29 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.3 Hz, 1H), 2.54 (s, 3H), 2.30 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 186.0, 177.7, 163.7, 152.9, 142.3, 141.1, 139.8, 129.8, 129.6, 129.4, 128.9, 128.8, 128.6, 127.6, 127.1, 126.6, 122.8, 120.0, 21.9, 21.8 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 131.0, 128.6, 128.4, 128.3, 127.8, 127.6, 127.4, 126.9, 126.4, 125.9, 20.8, 20.7 ppm.; HRMS (ESI): calcd for C33H22N2O (M + H) m/z = 463.1810; found = 463.1810.

(E)-4-(7,8-Dichloro-11H-indeno­[1,2-b]­quinoxalin-11-ylidene)-2,3-di-p-tolylcyclobut-2-en-1-one (3d)

Nature: bright yellow solid; yield: 38%; R f (8% EtOAc-hexane): 0.80; FTIR (KBr) υmax: 2928, 1760, 1526, 1449, 1109, 769, 679, 530, 470 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.88 (d, J = 7.9 Hz, 1H), 8.04 (d, J = 5.8 Hz, 2H), 7.76 (d, J = 8.1 Hz, 2H), 7.59–7.50 (m, 1H), 7.39 (t, J = 7.2 Hz, 1H), 7.36–7.29 (m, 4H), 7.12 (d, J = 8.0 Hz, 2H), 6.92 (s, 1H), 2.59 (s, 3H), 2.32 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 185.7, 177.7, 154.3, 153.4, 142.6, 140.9, 139.9, 139.5, 134.4, 133.2, 132.3, 132.3, 132.2, 130.2, 129.8, 129.4, 128.9, 128.9, 128.1, 127.3, 127.0, 126.5, 122.5, 22.0, 21.7 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 132.3, 130.1, 129.8, 129.4, 128.9, 128.1, 127.3, 127.0, 122.4, 22.0, 21.7 ppm.; HRMS (ESI): calcd for C33H20N2O (M) m/z = 530.0953; found = 530.0955.

(E)-2,3-bis­(3-Fluorophenyl)-4-(11H-indeno­[1,2-b]­quinoxalin-11-ylidene)­cyclobut-2-en-1-one (3e)

Nature: bright yellow solid; yield: 37%; R f (8% EtOAc-hexane): 0.83; FTIR (KBr) υmax: 2923, 1753, 1650, 1461, 1258, 1007, 679, 745, 691, 542 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 1H NMR (400 MHz, CDCl3): δ 8.59 (d, J = 7.8 Hz, 1H), 8.25 (s, 1H), 8.13 (dd, J = 6.9, 0.7 Hz, 1H), 8.11–8.06 (m, 2H), 7.96–7.92 (m, 1H), 7.84–7.81 (m, 2H), 7.74–7.62 (m, 2H), 7.56–7.50 (m, 2H), 7.51–7.42 (m, 2H), 7.31–7.23 (m, 1H), 7.19 (s, 1H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 190.6, 164.3, 161.8, 153.7, 153.4, 143.3, 141.9, 140.1, 138.4, 137.4, 132.3, 131.9, 130.6, 130.4, 129.0, 129.5, 129.4, 128.2, 124.8, 121.2, 120.8, 120.6, 115.6, 115.4 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 130.6, 130.4, 129.9, 129.5, 129.4, 129.1, 128.2, 124.8, 122.3, 121.2, 120.8, 120.6, 115.6115.4 ppm.; HRMS (ESI): calcd for C31H16F2N2O (M + H) m/z = 471.1309; found = 471.1311.

(E)-11-(1,2-Dimethoxy-2-phenylethylidene)-11H-indeno­[1,2-b]­quinoxaline (4a)

Nature: purple solid; yield: 35%; R f (8% EtOAc-hexane): 0.85; FTIR (KBr) υmax: 2907, 1737, 1613, 1446, 1337, 1178, 1809, 966, 695, 566 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.25 (t, J = 7.1 Hz, 2H), 8.13 (s, 1H), 8.07 (dd, J = 8.1, 1.3 Hz, 1H), 7.94–7.88 (m, 1H), 7.59–7.52 (m, 2H), 7.50–7.45 (m, 3H), 7.40 (dd, J = 7.9, 7.0 Hz, 1H), 7.25 (t, J = 7.6 Hz, 2H), 7.18 (d, J = 7.0 Hz, 1H), 3.89 (s, 3H), 3.61 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 162.6, 153.5, 152.5, 141.0, 140.7, 140.5, 139.0, 133.1, 131.3, 129.4, 129.0, 128.8, 128.6, 128.4, 127.5, 127.3, 125.9, 125.5, 122.1, 114.8, 58.7, 57.6 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 131.3, 129.4, 129.0, 128.6, 128.4, 127.5, 127.3, 125.9, 125.6, 122.1, 58.7, 57.6 ppm.; HRMS (ESI): calcd for C25H20N2O2 (M + H) m/z = 381.1603; found = 381.1606.

(E)-11-(2-(3-Fluorophenyl)-1,2-dimethoxyethylidene)-11H-indeno­[1,2-b]­quinoxaline (4b)

Nature: purple solid; yield: 30%; R f (8% EtOAc-hexane): 0.87; FTIR (KBr) υmax: 2928, 1735, 1610, 1508, 1345, 1246, 1061, 989, 769, 608, 465 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.26 (t, J = 7.6 Hz, 2H), 8.11 (s, 1H), 8.11–8.06 (m, 1H), 7.95–7.90 (m, 1H), 7.63–7.54 (m, 2H), 7.53–7.47 (m, 1H), 7.46–7.40 (m, 1H), 7.28–7.23 (m, 1H), 7.21–7.17 (m, 2H), 6.92–6.83 (m, 1H), 3.90 (s, 3H), 3.61 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 161.5, 153.3, 152.5, 141.8, 141.7, 140.8, 140.2, 133.2, 131.2, 130.1, 130.0, 129.3, 129.0, 128.9, 128.6, 128.4, 127.6, 125.8, 122.0, 121.1, 121.1, 115.0, 114.2, 114.0, 112.8, 76.7, 58.6, 57.5 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 131.2, 130.1, 130.0, 129.3, 129.0, 128.6, 128.4, 127.6, 125.8, 122.0, 121.1, 121.1, 114.2, 114.0, 112.8, 112.6, 76.9, 58.6, 57.5 ppm.; HRMS (ESI): calcd for C25H19FN2O2 (M + H) m/z = 399.1509; found = 399.1511.

(E)-11-(1,2-Dimethoxy-2-(4-nitrophenyl)­ethylidene)-11H-indeno­[1,2-b]­quinoxaline (4c)

Nature: purple solid; yield: 32%; R f (8% EtOAc-hexane): 0.85; FTIR (KBr) υmax: 2910, 1741, 1592, 1515, 1461, 1347, 1180, 1049, 995, 751, 566, 458 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.25 (t, J = 7.1 Hz, 2H), 8.13 (s, 1H), 8.07 (dd, J = 8.1, 1.3 Hz, 1H), 7.94–7.88 (m, 1H), 7.59–7.51 (m, 2H), 7.50–7.43 (m, 3H), 7.40 (dd, J = 7.9, 7.0 Hz, 1H), 7.25 (t, J = 7.6 Hz, 2H), 7.16 (dd, J = 13.3, 5.7 Hz, 1H), 3.89 (s, 3H), 3.61 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 160.3, 153.2, 152.8, 147.3, 146.8, 141.2, 140.8, 139.9, 133.6, 131.4, 129.3, 129.3, 128.9, 128.7, 128.6, 128.0, 126.6, 126.0, 125.9, 123.9, 122.1, 115.9, 77.4, 58.7, 57.7 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 131.4, 129.4, 129.2, 128.9, 128.7, 128.0, 126.6, 126.0, 123.9, 122.1, 77.1, 58.7, 57.7 ppm.; HRMS (ESI): calcd for C25H19N3O4 (M + H) m/z = 426.1454; found = 426.1486.

(E)-7,8-Dichloro-11-(1,2-dimethoxy-2-henylethylidene)-11H-indeno­[1,2-b]­quinoxaline (4d)

Nature: purple solid; yield: 37%; R f (8% EtOAc-hexane): 0.85; FTIR (KBr) υmax: 2928, 1730, 1598, 1449, 1329, 1192, 1103, 697, 572 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.25 (d, J = 7.6 Hz, 2H), 8.20 (s, 1H), 8.13 (d, J = 8.6 Hz, 2H), 8.09 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.69–7.62 (m, 2H), 7.58 (dd, J = 15.0, 7.1 Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.4 Hz, 1H), 3.86 (s, 3H), 3.63 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 160.3, 153.2, 152.8, 147.3, 146.8, 141.2, 140.8, 140.0, 133.6, 131.4, 129.4, 129.3, 128.9, 128.7, 128.0, 126.6, 126.1, 123.9, 122.1, 115.9, 77.2, 58.7, 57.8 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 131.4, 129.4, 129.3, 128.9, 128.7, 128.0, 126.6, 126.1, 123.9, 122.1, 77.2, 58.7, 57.8 ppm.; HRMS (ESI): calcd for C25H18Cl2N2O2 (M + H) m/z = 449.0824; found = 449.0828.

11-Methoxy-11-(phenylethynyl)-11H-indeno­[1,2-b]­quinoxaline (5a)

Nature: white solid; yield: 47%; R f (8% EtOAc-hexane): 0.85; FTIR (KBr) υmax: 2935, 1580, 1502, 1341, 1061, 852, 751, 488 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.12 (d, J = 7.7 Hz, 1H), 8.05 (dd, J = 15.0, 7.3 Hz, 2H), 7.81 (d, J = 6.7 Hz, 1H), 7.68–7.57 (m, 2H), 7.55–7.45 (m, 2H), 7.37 (d, J = 6.0 Hz, 2H), 7.16 (d, J = 6.7 Hz, 3H), 3.59 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 159.0, 153.2, 146.2, 143.0, 141.6, 136.5, 132.3, 132.1, 130.3, 130.1, 129.3, 129.2, 128.9, 128.2, 125.7, 122.5, 121.9, 87.2, 85.1, 77.0, 53.7 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 132.3, 132.1, 130.8, 130.3, 130.0, 129.3, 128.9, 128.2, 125.7, 122.5 ppm.; HRMS (ESI): calcd for C24H16N2O (M + H) m/z = 349.1341; found = 349.1346.

11-((3-Fluorophenyl)­ethynyl)-11-methoxy-11H-indeno­[1,2-b]­quinoxaline (5b)

Nature: white solid; yield: 43%; R f (8% EtOAc-hexane): 0.85; FTIR (KBr) υmax: 2941, 1680, 1568, 1443, 1341, 1043, 917, 751, 685, 500 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.13–8.08 (m, 1H), 8.08–7.99 (m, 2H), 7.81–7.76 (m, 1H), 7.67–7.55 (m, 2H), 7.54–7.43 (m, 2H), 7.15–7.11 (m, 2H), 7.11–7.02 (m, 1H), 6.92–6.81 (m, 1H), 3.57 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 163.4, 160.9, 158.7, 153.2, 145.9, 143.0, 141.6, 136.5, 132.4,131.3, 131.2, 130.9, 130.4, 130.0, 129.9, 129.8, 129.3, 129.2, 128.0, 125.6, 122.5, 119.0, 118.8, 116.4, 116.2, 86.2, 85.8, 85.7, 53.7 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 130.2, 130.9, 130.4, 130.0, 129.9, 129.8, 129.3, 129.2, 129.1, 128.0, 128.0, 125.6, 122.5, 119.0, 118.8, 116.4, 116.2, 53.7 ppm.; HRMS (ESI): calcd for C24H15FN2O (M + H) m/z = 367.1247; found = 367.1249.

11-Methoxy-11-((4-nitrophenyl)­ethynyl)-11H-indeno­[1,2-b]­quinoxaline (5c)

Nature: light brown solid; yield: 50%; R f (8% EtOAc-hexane): 0.85; FTIR (KBr) υmax: 2896, 1660, 1572, 1437, 1337, 1048, 936, 748, 683, 507 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.15 (dd, J = 8.1, 1.4 Hz, 1H), 8.14–8.10 (m, 1H), 8.10–8.05 (m, 3H), 7.84–7.80 (m, 1H), 7.75–7.66 (m, 2H), 7.60–7.51 (m, 4H), 3.56 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 158.4, 153.3, 147.5, 145.4, 143.1, 141.7, 136.8, 133.0, 132.6, 131.2, 130.7, 130.1, 129.6, 129.3, 128.8, 125.8, 123.6, 122.8, 90.7, 84.8, 77.0, 53.9 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 132.9, 132.4, 131.1, 130.6, 130.0, 129.5, 129.2, 125.6, 123.5, 122.6, 53.7 ppm.; HRMS (ESI): calcd for C24H15N3O3 (M + H) m/z = 394.1192; found = 394.1193.

7,8-Dichloro-11-methoxy-11-(phenylethynyl)-11H-indeno­[1,2-b]­quinoxaline (5d)

Nature: light brown solid; yield: 44%; R f (8% EtOAc-hexane): 0.85; FTIR (KBr) υmax: 2935, 2218, 1723, 1580, 1443, 1282, 1085, 912, 756, 673, 506 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.14 (dd, J = 8.1, 1.0 Hz, 1H), 8.12–8.09 (m, 1H), 8.09–8.04 (m, 3H), 7.85–7.79 (m, 1H), 7.73–7.65 (m, 2H), 7.58–7.53 (m, 3H), 3.56 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 158.3, 153.1, 147.4, 145.3, 141.6, 136.6, 132.9, 132.4, 131.1, 130.6, 130.0, 129.5, 129.2, 128.7, 125.6, 123.4, 122.6, 90.6, 84.7, 53.7 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 132.4, 131.1, 130.6, 130.0, 129.5, 129.2, 125.6, 123.4, 122.6, 53.7 ppm.; HRMS (ESI): calcd for C24H14Cl2N2O (M + H) m/z = 417.0561; found = 417.0562.

1-Methoxy-2-phenyl-2a,7-diazabenzocyclopentafluorene (6a)

Nature: red solid; yield: 40%; R f (8% EtOAc-hexane): 0.85; FTIR (KBr) υmax: 2924, 1588, 1422, 1262, 1168, 1014, 832, 751 cm–1.; 1H NMR (400.3 MHz, CDCl3/TMS): δ 8.28 (d, J = 8.3 Hz, 1H), 8.11 (d, J = 7.4 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 7.1 Hz, 2H), 7.56–7.41 (m, 5H), 7.40–7.29 (m, 2H), 7.21 (d, J = 7.5 Hz, 1H), 4.20 (s, 3H) ppm.; 13C NMR (100.6 MHz, CDCl3/TMS): δ 139.8, 131.3, 130.8, 130.5, 128.6, 128.3, 127.6, 126.9, 125.1, 124.6, 121.4, 116.5, 60.9 ppm.; DEPT-135 (100.6 MHz, CDCl3/TMS): δ 131.3, 130.9, 130.8, 129.0, 128.7, 128.6, 125.1, 124.6, 124.0, 121.4, 116.5, 60.9 ppm.; HRMS (ESI): calcd for C24H16N2O (M + H) m/z = 349.1341; found = 349.1344.

Supplementary Material

ao5c11174_si_001.pdf (6.4MB, pdf)

Acknowledgments

A.J.C.P. thanks VIT, Vellore for the TRA fellowship. S.K. thanks VIT Management for providing infrastructure, instrumental facilities.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.5c11174.

  • Experimental section; Scanned copies of 1H NMR, 13C NMR, DEPT-135 NMR, IR, and HRMS spectrum for all the new compounds; and primary single-crystal XRD data for compounds 3a, 3d, 4b, 5c, and 6a (PDF)

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Vellore Institute of Technology (VIT), Vellore under the Faculty Seed Grant (RGEMS) to S.K. (Sanction Order No.: SG20250056).

The authors declare no competing financial interest.

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