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. 2020 Mar 3;5(10):5436–5442. doi: 10.1021/acsomega.0c00045

Expeditious Green Synthesis of Novel 4-Methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one Analogue from Ninhydrin: N/S-Alkylation and Aza-Michael Addition

Ahmed T A Boraei †,*, Hazem A Ghabbour ‡, Ahmed A M Sarhan §, Assem Barakat ∥,⊥,*
PMCID: PMC7081446  PMID: 32201835

Abstract

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A straightforward green synthesis of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 6 is reported from ninhydrin 1 via condensation with ethyl acetoacetate, followed by cyclization with hydrazine hydrate in water as a benign solvent. Tetraazafluoranthen-3-thione 7 was obtained using Lawesson’s reagent. N-alkylated tetraazafluoranthen-3-one 8–12 and S-alkylated analogues 13–15 were synthesized via alkylation. The investigation of the unique reactivity of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one/thione toward the alkylation and aza-Michael additions was explored.

Introduction

Fluoranthenes represent an intriguing class of polycyclic aromatic compounds with remarkable and interesting applications.1−3 Considerable research has focused on their sensing as well as organic electronics applications4 and related natural products. Many fungal natural products contain a fluoranthene in their structures, for example, hortein5 and daldinone E.6 Moreover, FLUN-550 was introduced as a fluoranthene-based fluorescent probe for selective staining of intracellular lipid droplets.6 Synthesis and derivatization of fluoranthenes have received much attention in the recent years. Diels–Alder reaction7−10 and transition metal-catalyzed reactions are the most commonly used methods for their synthesis.11−22

The vast majority of reported fluoranthenes were synthesized from 1,8-dichloronaphthalenes and arylboronic acids in the presence of Pd catalyst under the conditions of high catalyst loading [20 mol % Pd2(dba)3] and high reaction temperatures (155–175 °C).23 Synthesis of fluoranthenes was accomplished via inter- and intramolecular C–H arylation in three steps in the presence of Pd catalyst.24 Substituted fluoranthenes were obtained selectively via Suzuki–Miyaura reaction using tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) and Pd(dppf)Cl2 catalysts starting from 1,8-diiodonaphthalene.25

Fluoranthenes aza analogues were also synthesized by Koutentis and co-workers via an oxidative and nonoxidative cyclization protocol.26

Herein, we report a novel, straightforward, simple, effective, and catalyst free method for the synthesis of tetraazafluoranthen-3-one in a short time. In addition, to the best of our knowledge, there are no literature reports for the construction of tetraazafluoranthen-3(2H)-one so far (Figure 1).

Figure 1.

Figure 1

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Results and Discussion

As part of our current studies on the development of new routes in heterocyclic synthesis,28−35 here we focused on the synthesis of new heterocyclic systems from ninhydrin. Stirring ninhydrin 1 with ethyl acetoacetate 2 in water for 15 min afforded ethyl indeno[1,2-b]furan-3-carboxylate 3 in excellent yield.33 Reaction of 3 with hydrazine hydrate in water or ethanol and reflux for 10 min, interestingly, afforded tetraazafluoranthen-3(2H)-one 6 in good yield. Heating of 3 with thiourea, surprisingly, gave indeno-imidazole 4 (Scheme 1). The plausible reaction mechanism of the formation of 4 by nucleophilic ring opening/ring closer via the intermediate was followed by removal of ethyl acetoacetate, as shown in Scheme 1.

Scheme 1. Synthesis of Indeno-Imidazole 4 and Tetraazafluoranthen-3(2H)-one 6.

Scheme 1

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The suggested mechanism for the formation of tetraazafluoranthen-3(2H)-one 6 involves, at first, condensation of ethyl acetoacetate with ninhydrin to give ethyl indeno[1,2-b]furan-3-carboxylate 3, which was attacked by two hydrazine molecules at the carbonyl carbon (C4) and the carbon (C8b), leading to cleavage of the furan ring with the loss of four water molecules and EtOH. During this process, recyclization occurs to form tetraazafluoranthen-3-one (Scheme 2). The structure of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 6 was deduced from its nuclear magnetic resonance (NMR) spectra, which showed the methyl protons at 2.99 ppm and four aromatic protons between 7.96 and 8.19 ppm, in addition to one deshielded signal at 13.29 ppm, which was assigned for NH. The methyl carbon appeared at 21.26 ppm in addition to 12 aromatic carbons including C=O, which appeared between 119.10 and 158.94 ppm.

Scheme 2. Proposed Mechanism for the Formation of Tetraazafluoranthen-3-one 6.

Scheme 2

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Reaction of ninhydrin with thiourea and thiosemicarbazide in water and reflux for 10 min were performed to afford the crystalline compounds indeno-imidazole 4 and 1-amino-indeno-imidazole 5, respectively, in good yield (Scheme 3).

Scheme 3. Synthesis of 2-Thioxo-tetrahydroindeno[2,1-d]imidazol-ones 4 and 5.

Scheme 3

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Thionation of tetraazafluoranthen-3-one 6 was achieved using Lawesson’s reagent in dry toluene to produce tetraazafluoranthen-3-thione 7 in good yield (Scheme 4). The desired thione 7 did not form utilizing P2S5 and pyridine. 4-Methyl-tetraazafluoranthene-3-thione 7 structure was confirmed from the NMR spectra, which showed the NH proton at 14.76 ppm and the thiocarbonyl carbon at 181.43 ppm.

Scheme 4. Thionation of 6 to Afford Tetraazafluoranthen-3-thione 7.

Scheme 4

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Given the uniqueness of tetraazafluoranthen-3-one 6 and 7, we have also explored their reactivity in further synthetic transformations including N/S-alkylation and aza-Michael additions.

Coupling of tetraazafluoranthen-3-one 6 with allyl bromide, ethyl chloroacetate, benzyl bromide, amyl bromide, and phenacyl bromide in the presence of K2CO3 in acetone and dimethyl formamide (DMF) afforded the N-alkylated products 8–12 in good yields (Scheme 5).

Scheme 5. Synthesis of N-Alkylated Tetraazafluoranthen-3-one 8–12.

Scheme 5

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N-alkylation products 8–12 were confirmed from the loss of the NH signal. Further, aza- not or oxa-alkylation of tetraazafluoranthen-3-one was confirmed by single-crystal X-ray diffraction analysis for 8.

From the above-mentioned experiment, other analogues of S-alkylated tetraazafluoranthen-3-one 13–15 were explored. Coupling of 7 with allyl bromide, ethyl chloroacetate, and benzyl bromide afforded the S-alkylated products 13–15, respectively (Scheme 6). S-alkylation of 7 was confirmed from the S–CH2–carbon signals around 33.00 ppm to yield 13–15.

Scheme 6. Synthesis of S-Alkylated Tetraazafluoranthen-3-one 13–15.

Scheme 6

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Aza-Michael addition of 6 or 7 as Michael donor to acrylonitrile and methyl acrylate as Michael acceptors in DMF/EtOH containing Et3N leads to aza-Michael adduct 16–18 (Scheme 7).

Scheme 7. Aza-Michael Addition and Synthesis of Tetraazafluoranthen-3-one Scaffold 16–18.

Scheme 7

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Aza- not thia-Michael addition was deduced from the methylene signal 54.22 ppm and thiocarbonyl carbon (C=S) at 180.08 ppm. Additionally, single-crystal X-ray analysis of compound 16 was performed.

Interestingly, chlorination of 6 by reflux in POCl3 led to chlorination of methyl branch to provide the halogenated compound 19, whereas compound 20 was not obtained (Scheme 8).

Scheme 8. Chlorination of 6 Using POCl3.

Scheme 8

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Chlorination of the methyl group in 19 was deduced from the disappearance of the proton and carbon methyl signals; on the other hand, a new carbon signal appeared at 95.46 ppm corresponding to the highly deshielded −CCl3. The NH proton signal was found at 13.44 ppm. The plausible mechanism for the formation of compound 19 proceeds via typical free radical substitution reaction (Scheme 9).36,37

Scheme 9. Proposed Mechanism for Compound 19.

Scheme 9

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Conclusions

In conclusion, green syntheses of indeno-imidazole, 1-amino-indeno-imidazole, and tetraazafluoranthen-3-one were achieved in water, starting from ninhydrin. Compound 4 was formed via nucleophile ring opening and closer. Tetraazafluoranthen-3-one 6 was converted to tetraazafluoranthen-3-thione 7 using Lawesson’s reagent. In addition, a set of N/S-alkylations of tetraazafluoranthen-3-one analogue were performed. Aza-Michael addition was also investigated. Further studies are underway in our laboratory.

Experimental Section

General Information

All reactions were monitored by thin-layer chromatography (TLC) using aluminum-backed plates precoated with silica gel (60 Å, F254). Visualization of spots was detected using ultraviolet light. NMR spectra were measured on a Bruker spectrometer at 400 MHz for 1H NMR spectra and at 100 MHz for 13C NMR spectra calibrated with (tetramethylsilane, 0 ppm) as the internal standard.

Synthesis of 3

Ethyl 3a,8b-dihydroxy-2-methyl-4-oxo-3a,8b-dihydro-4H-indeno[1,2-b]furan-3-carboxylate 3 was synthesized according to a known procedure.27

Synthesis of Indeno[2,1-d]imidazolones 4 and 5

Method A: General Method for the Synthesis of 4 and 5

A mixture of ninhydrin (1.0 mmol) and the appropriate thioamide (thiourea and thiosemicarbazide) (1.1 mmol) was refluxed in 5.0 mL of water for 10 min until the reaction was completed (monitored by TLC). The crystals formed were hot; they were left to cool and then collected by filtration and recrystallized from ethanol.

Method B: For the Synthesis of 4

A mixture of ninhydrin (1.0 mmol) and ethyl acetoacetate (1.5 mmol) in 10 mL of water was stirred at room temperature for 15 min. A white solid was formed, which was collected by filtration and dried to give 3 in 98% yield, mp 89–90 °C. Compound 3 (1.0 mmol) was refluxed with thiourea (1.0 mmol) in 5.0 mL of water for 30 min and left to cool. The white precipitate formed was collected by filtration, dried, and recrystallized from ethanol.

3a,8a-Dihydroxy-2-thioxo-1,2,3,3a-tetrahydroindeno[2,1-d]imidazol-8(8aH)-one 4

Yield: 96%method A, 71%method B as colorless crystals, mp 221–222 °C. 1H NMR (DMSO-d6, 500 MHz): δ 6.87 (s, 1H, OH), 6.95 (s, 1H, OH), 7.63–7.66 (m, 1H, arom), 7.78 (d, 1H, J 7.5 Hz, arom), 7.82 (d, 1 H, J 7.5 Hz, arom), 7.89–7.91 (m, 1H, arom), 9.51 (s, 1H, NH), 9.80 (s, 1H, NH); 13C NMR (DMSO-d6, 125 MHz): δ 90.10, 90.62 (2C, aliph), 124.08, 125.86, 130.99, 132.89, 137.42, 151.32 (6C, arom), 178.74 (C=S), 196.8 (C=O); CHN analysis calcd for [C10H8N2O3S]: C, 50.84; H, 3.41; N, 11.86; S, 13.57. Found: C, 50.64; H, 3.31; N, 11.76; S, 13.61.

1-Amino-3a,8a-dihydroxy-2-thioxo-1,2,3,3a-tetrahydroindeno[2,1-d]imidazol-8(8aH)-one 5

Yield: 85%method A as colorless crystals, mp 201–202 °C. 1H NMR (DMSO-d6, 600 MHz): δ 4.48 (s, 2H, NH2), 6.93 (s, 1H, OH), 7.35 (s, 1H, OH), 7.64–7.66 (m, 1H, arom), 7.77 (d, 1H, J 7.5 Hz, arom), 7.83 (d, 1H, J 7.5 Hz, arom), 7.88–7.90 (m, 1H, arom), 9.97 (s, 1H, NH); 13C NMR (DMSO-d6, 125 MHz): δ 87.97, 90.86 (2C, aliph), 123.93, 125.68, 131.03, 132.76, 137.19, 150.70 (6C, arom), 179.20 (C=S), 194.49 (C=O). CHN analysis calcd for [C10H9N3O3S]: C, 47.80; H, 3.61; N, 16.72; S, 12.76. Found: 47.92; H, 3.81; N, 16.65; S, 12.93.

Synthesis of 4-Methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 6

A mixture of 3 [3.0 g] and hydrazine hydrate [5.0 mL] was refluxed in water or ethanol [5.0 mL] for 15 min. A gray precipitate appeared. Then, the reaction mixture was left to cool, and the precipitate was collected by filtration, dried, and recrystallized from DMF.

Yield: 54%, mp 315–316 °C; 1H NMR (DMSO-d6, 600 MHz): δ 2.99 (s, 3H, CH3), 7.66 (m, 2H, aromatic), 7.96 (d, 1H, J 6.3 Hz, aromatic), 8.17 (d, 1H, J 6.1 Hz, aromatic), 13.29 (s, 1H, NH); 13C NMR (DMSO-d6, 150 MHz): δ 21.26 (CH3), 119.10, 123.11, 123.62, 126.53, 131.67, 132.59, 135.55, 137.82, 145.17, 156.77, 158.06, 158.94 (12Caromatic); CHN analysis calcd for C13H8N4O [236.0698]: C, 66.10; H, 3.41; N, 23.72. Found: C, 66.06; H, 3.66; N, 23.66.

4-Methyl-1,2,5,6-tetraazafluoranthene-3(2H)-thione 7

A mixture of 6 (1.0 mmol) and Lawesson’s reagent (1.1 mmol) was refluxed in toluene for 4 h. A brownish precipitate formed, which was filtered while hot and recrystallized from DMF/EtOH.

Yield: 43%, mp 280−281 °C; 1H NMR (DMSO-d6, 400 MHz): δ 3.16 (s, 3H, CH3), 7.70 (m, 24H, aromatic), 8.03 (m, 1H, aromatic), 8.19 (m, 1H, aromatic), 14.76 (s, 1H, NH); 13C NMR (DMSO-d6, 100 MHz): δ 23.64 (CH3), 120.99, 123.53, 123.76, 125.13, 132.49, 132.60, 135.06, 137.66, 149.79, 157.68, 159.41 (11Caromatic), 181.43 (C=S); CHNS analysis calcd for C13H8N4S [252.0470]: C, 61.71; H, 3.45; N, 22.21; S, 12.71. Found: C, 61.89; H, 3.20; N, 21.87; S, 12.41.

General Procedures for the N/S-Alkylation of 8–12 and 13–15

A mixture of the selected nucleophile 6 or 7 (1.0 mmol) and K2CO3 (1.1 mmol) in dry acetone/DMF (10:2 mL) was stirred for 1 h. Then, the appropriate alkyl halide (1.1 mmol) was added portion wise, and stirring was continued overnight. The solvent was removed under vacuum; water was added; the solid was filtered, dried, and recrystallized from EtOH or DMF/EtOH.

2-Allyl-4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 8

Yield: 85%EtOH, mp 208–209 °C; 1H NMR (DMSO-d6, 600 MHz): δ 3.02 (s, 3H, CH3), 4.85 (d, 2H, J 5.3 Hz, NCH2–CH=CH2), 5.24 (d, 1H, J 10.4 Hz, NCH2–CH=CHcisHtrans), 5.28 (d, 1H, J 17.2 Hz, NCH2–CH=CHcisHtrans), 6.02–6.08 (ddt, 1H, J 17.2, 10.4, 5.3 Hz, NCH2–CH=CH2), 7.67–7.70 (m, 2H, aromatic), 7.99–8.00 (m, 1H, aromatic), 8.21–8.22 (m, 1H, aromatic); 13C NMR (DMSO-d6, 150 MHz): δ 20.33 (CH3), 54.67 (NCH2), 118.21, 118.51, 123.29, 123.74, 126.24, 131.93, 132.66, 133.09, 135.45, 137.85, 144.77, 156.87, 157.40, 158.17 (14C12aromatic+2vinylic); CHN analysis calcd for C16H12N4O [276.1011]: C, 69.55; H, 4.38; N, 20.28. Found: C, 69.15; H, 4.25; N, 20.27.

2-Ethoxycarbonylmethyl-4-methyl-1,2,5,6-tetraazaflouranthen-3(2H)-one 10

Yield: 74%DMF/EtOH, mp 230–231 °C; 1H NMR (DMSO-d6, 600 MHz): δ 1.25 (t, 3H, CH3), 3.01 (s, 3H, CH3), 4.21 (q, 2H, CH2ester), 5.05 (s, 2H, NCH2), 7.69–7.71 (m, 2H, aromatic), 7.99–8.00 (m, 1H, aromatic), 8.22–8.24 (m, 1H, aromatic); 13C NMR (DMSO-d6, 150 MHz): δ 14.47 (CH3), 21.26 (CH3), 54.52 (NCH2), 61.74 (OCH2), 118.26, 123.47, 123.86, 126.51, 132.27, 132.79, 135.12, 138.02, 145.09, 156.74, 157.72, 258.20 (12Caromatic), 168.05 (C=Oester); CHN analysis calcd for C17H14N4O3 [322.1066]: C, 63.35; H, 4.38; N, 17.38. Found: C, 63.21; H, 4.55; N, 17.25.

2-Benzyl-4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 10

Yield: 71%DMF/EtOH, mp 217–218 °C; 1H NMR (DMSO-d6, 400 MHz): δ 3.01 (s, 3H, CH3), 5.44 (s, 2H, NCH2), 7.29–7.43 (m, 5H, Phenyl), 7.67–7.69 (m, 2H, aromatic), 7.98–8.00 (m, 1H, aromatic), 8.19–8.22 (m, 1H, aromatic); 13C NMR (DMSO-d6, 100 MHz): δ 21.28 (CH3), 55.72 (NCH2), 118.58, 123.30, 123.67, 126.24, 128.00, 128.23, 128.95, 131.94, 132.58, 135.39, 137.19, 137.91, 144.93, 156.86, 157.65, 158.14 (18Caromatic); CHN analysis calcd for C20H14N4O [326.1168]: C, 73.61; H, 4.32; N, 17.17. Found: C, 73.90; H, 4.53; N, 17.18.

4-Methyl-2-pentyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 11

Yield: 65%DMF/EtOH, mp 145–146 °C; 1H NMR (DMSO-d6, 600 MHz): δ 0.90 (s, 3H, CH3), 1.36–1.37 (m, 4H, 2CH2), 1.81–1.83 (m, 2H, CH2), 3.03 (s, 3H, CH3), 4.23 (t, 2H, NCH2), 7.68–7.69 (m, 2H, aromatic), 8.00–8.02 (m, 1H, aromatic), 8.21–8.22 (m, 1H, aromatic); 13C NMR (DMSO-d6, 150 MHz): δ 14.21 (CH3), 21.30 (CH3), 22.22, 28.28, 28.65 (3CH2), 52.35 (NCH2), 118.27, 123.12, 123.66, 125.90, 131.78, 132.58, 135.49, 137.72, 144.26, 156.84, 157.74, 158.09 (12Caromatic); CHN analysis calcd for C18H18N4O [306.1481]: C, 70.57; H, 5.92; N, 18.29. Found: C, 70.52; H, 5.88; N, 18.14.

4-Methyl-2-phenacyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 12

Yield: 75%DMF, mp 222−223 °C; 1H NMR (DMSO-d6, 400 MHz): δ 2.99 (s, 3H, CH3), 5.84 (s, 2H, NCH2), 7.60–7.76 (m, 5H, aromatic), 7.90–7.91 (m, 1H, aromatic), 8.11–8.16 (m, 3H, aromatic); 13C NMR (DMSO-d6, 100 MHz): δ 21.26 (CH3), 59.52 (NCH2), 118.23, 123.42, 123.88, 128.61, 129.49, 132.17, 132.80, 134.64, 135.25, 137.94, 145.0, 156.83, 157.72, 158.13 (18Caromatic), 193.24 (C=O); CHN analysis calcd for C21H14N4O2 [354.1117]: C, 71.18; H, 3.98; N, 15.81. Found: C, 70.93; H, 4.18; N, 16.06.

3-(Allylsulfanyl)-4-methyl-1,2,5,6-tetraazafluoranthene 13

Yield: 84%EtOH, mp 151–152 °C; 1H NMR (DMSO-d6, 400 MHz): δ 3.05 (s, 3H, CH3), 4.21 (d, 2H, J 6.9 Hz, SCH2CH=CHcisHtrans), 5.25 (d, 1H, J 10.0 Hz, SCH2CH=CHcisHtrans), 5.50 (dd, 1H, J 17.0 Hz, Jgem 1.4 Hz, SCH2CH=CHcisHtrans), 6.05–6.15 (ddt, 1H, J 17.0, 10.0, 6.9 Hz, SCH2–CH=CH2), 7.69–7.71 (m, 2H, aromatic), 8.13–8.19 (m, 2H, aromatic); 13C NMR (DMSO-d6, 100 MHz): δ 24.02 (CH3), 33.62 (SCH2), 117.78, 119.86, 120.50, 124.10, 124.28, 132.84, 132.98, 137.42, 154.72, 157.65, 157.74, 159.01 (14Caromatic+vinyl); CHNS analysis calcd for C16H12N4S [292.0783]: C, 65.73; H, 4.14; N, 19.16; S, 10.97. Found: C, 65.53; H, 4.43; N, 19.03; S, 10.79.

3-(Ethoxycarbonylmethyl)-4-methyl-1,2,5,6-tetraazafluoranthene 14

Yield: 79%EtOH, mp 200 °C; 1H NMR (DMSO-d6, 600 MHz): δ 1.24 (t, 3H, CH3), 3.10 (s, 3H, CH3), 4.19 (q, 2H, CH2ester), 4.39 (s, 2H, SCH2), 7.71–7.72 (m, 2H, aromatic), 8.18–8.21 (m, 2H, aromatic); 13C NMR (DMSO-d6, 150 MHz): δ 14.54 (CH3), 23.81 (CH3), 33.68 (SCH2), 61.71 (OCH2), 117.66, 120.55, 124.31, 133.01, 137.41, 137.56, 154.55, 156.95, 158.02, 159.05 (13Caromatic), 168.31 (C=O); CHNS analysis calcd for C17H14N4O2S [338.0837]: C, 60.34; H, 4.17; N, 16.56; O, 9.46; S, 9.48. Found: C, 60.26; H, 4.2; N, 16.66; S, 9.52.

3-(Benzylsulfanyl)-4-methyl-1,2,5,6-tetraazafluoranthene 15

Yield: 90%EtOH, mp 198–199 °C; 1H NMR (DMSO-d6, 600 MHz): δ 3.05 (s, 3H, CH3), 4.82 (s, 2H, SCH2Ph), 7.31 (t, 1H, Phenyl), 7.38 (t, 2H, phenyl), 7.59 (d, 2H, J 7.7 Hz, phenyl), 7.71–7.72 (m, 2H, aromatic), 8.18–8.21 (m, 2H, aromatic); 13C NMR (DMSO-d6, 150 MHz): δ 23.92 (CH3), 35.17 (SCH2), 117.58, 120.46, 124.07, 127.95, 132.76, 136.87, 137.44, 154.60, 157.92, 158.89 (18Caromatic+phenyl); CHNS analysis calcd for C20H14N4S [342.0939]: C, 70.15; H, 4.12; N, 16.36; S, 9.36. Found: C, 69.93; H, 4.18; N, 16.15; S, 9.18.

General Procedures for Michael Addition of 16–18

A mixture of the selected Michael donor 6 or 7 (1.0 mmol) and the appropriate Michael acceptor (1.0 mmol) was refluxed in ethanol/DMF 10:1 mL containing Et3N (2.0 mmol) for 6 h, cooled, and filtered. The precipitates were dried and recrystallized from ethanol.

2-Cyanoethyl-4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 16

Yield: 60%, mp 243–244 °C; 1H NMR (DMSO-d6, 600 MHz): δ 3.01 (s, 3H, CH3), 3.09 (t, 2H, −NCH2CH2CN), 4.47 (t, 2H, −NCH2CH2CN), 7.66–7.68 (m, 2H, aromatic), 7.92–7.93 (m, 1H, aromatic), 8.14–8.16 (m, 1H, aromatic); 13C NMR (DMSO-d6, 150 MHz): δ 16.93 (NCH2CH2CN), 21.28 (CH3), 47.91 (NCH2CH2CN), 118.21, 118.97, 123.39, 123.81, 126.02, 132.18, 132.76, 135.10, 137.71, 144.76, 156.66, 157.38, 157.96 (13C(aromatic+CN)); CHN analysis calcd for C16H11N5O [289.0964]: C, 66.43; H, 3.83; N, 24.21. Found: C, 66.77; H, 4.03; N, 24.02.

2-Methoxycarbonylethyl-4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 17

Yield: 60%, mp 139–140 °C; 1H NMR (DMSO-d6, 600 MHz): δ 2.88 (t, 2H, −NCH2CH2COOCH3), 2.99 (s, 3H, CH3), 3.64 (S, 3H, −NCH2CH2COOCH3), 4.45 (t, 2H, −NCH2CH2COOCH3), 7.65–7.67 (m, 2H, aromatic), 7.90–7.92 (m, 1H, aromatic), 8.14–8.16 (m, 1H, aromatic); 13C NMR (DMSO-d6, 150 MHz): δ 21.37 (CH3), 32.95 (NCH2CH2COOCH3), 48.12 (NCH2CH2COOCH3), 52.10 (NCH2CH2COOCH3), 118.30, 123.19, 123.77, 125.94, 131.98, 132.72, 135.25, 137.66, 144.39, 156.80, 157.48, 158.06 (12Caromatic), 171.60 (C=O); CHN analysis calcd for C17H14N4O3 [322.1066]: C, 63.35; H, 4.38; N, 17.38. Found: C, 63.34; H, 4.62; N, 17.25.

2-Cyanoethyl-4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-thione 18

Yield: 69%DMF/EtOH, mp 249−250 °C; 1H NMR (DMSO-d6, 600 MHz): δ 3.20 (s, 3H, CH3), 3.24 (t, 2H, −NCH2CH2CN), 5.03 (t, 2H, −NCH2CH2CN), 7.74–7.76 (m, 2H, aromatic), 8.08 (d, 1H, J 6.8 Hz, aromatic), 8.24 (d, 1H, J 7.0 Hz, aromatic); 13C NMR (DMSO-d6, 150 MHz): δ 15.68 (NCH2CH2CN), 24.61 (CH3), 54.22 (NCH2CH2CN), 118.67, 119.71, 123.79, 124.14, 125.76, 132.82, 133.17, 134.63, 137.82, 149.14, 158.01, 159.56 (12C(aromatic+CN)) 180.08 (C=S); CHN analysis calcd for C16H11N5S [305.0735]: C, 62.93; H, 3.63; N, 22.93; S, 10.50. Found: C, 62.83; H, 3.95; N, 22.71; S, 10.30.

4-(Trichloromethyl)-1,2,5,6-tetraazafluoranthen-3(2H)-one 19

Tetraazafluoranthen-3(2H)-one 6 (1.0 mmol) was refluxed in POCl3 (10 mL) for 3 h, left to cool, and added to ice water. The formed precipitate was collected, dried, and recrystallized from DMF/EtOH.

Yield: 84%DMF, mp 316–318 °C; 1H NMR (DMSO-d6, 400 MHz): δ 7.65 (t, 1H, aromatic), 7.72 (t, 1H, aromatic), 7.95 (d, 1H, J 7.4 Hz, aromatic), 8.21 (d, 1H, J 7.2 Hz, aromatic) 13.44 (s, 1H, NH); 13C NMR (DMSO-d6, 100 MHz): δ 95.46 (CCl3), 118.06, 123.07, 124.45, 129.77, 131.77, 133.96, 135.92, 136.84, 144.05, 153.04, 154.97 (11Caromatic), 162.09 (C=O); CHN analysis calcd for C13H5Cl3N4O [337.9529]: C, 45.98; H, 1.48; Cl, 31.32; N, 16.50. Found: C, 45.78; H, 1.51; Cl, 31.62; N, 16.59.

Acknowledgments

The authors would like to extend their sincere appreciation to the Researchers Supporting Project Number (RSP-2019/64), King Saud University, Riyadh, Saudi Arabia.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c00045.

  • Copies of 1H and 13C NMR spectra and X-ray data (PDF)

Author Contributions

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

The authors declare no competing financial interest.

Supplementary Material

ao0c00045_si_001.pdf (1.6MB, pdf)

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