1‐(Pyrrolidin‐1‐yl)naphtho[1,2‐d]isoxazole

1. Introduction

Benzo[d]isoxazole (or 1,2-benzisoxazole) is one of the most significant scaffolds in medicinal chemistry today. 3-Substituted benzo[d]isoxazoles display a broad range of bioactivities, including antimicrobial, anticonvulsant, antitubercular, antipsychotic, anticancer, antithrombotic and, acetylcholinesterase inhibition properties [1]. The importance of these compounds is further highlighted by United States FDA-approved drugs such as Zonisamide [2], an antiepileptic, and the antipsychotics, Risperidone [3] and Paliperidone [4]. The synthesis of benzo[d]isoxazoles has been adequately covered in the literature [5,6,7].

Naphtho[1,2-d]isoxazoles have been studied much less. The first derivative to be reported was the parent compound which was synthesized by the cyclodehydration of 2-hydroxy-1-naphthaldehyde oxime with acetic anhydride [8]. 2-Hydroxy-1-naphthaldehyde oxime was also cyclodehydrated to naphtho[1,2-d]isoxazole with TsCl and Et₃N [9]. During the synthesis of diazonaphthoquinones from the corresponding naphthols by diazo transfer from 2-azido-1,3-dimethylimidazolinium chloride, the use of

Figure 1. FDA-approved 3-substituted benzo[d]isoxazole drugs.

Figure 1. FDA-approved 3-substituted benzo[d]isoxazole drugs.

2-hydroxy-1-naphthaldehyde afforded naphtho[1,2-d]isoxazole and 1-diazo-2(1H)naph-thalenone in 70 and 10% yields, respectively [10,11]. The azido complex derived from 2-hydroxy-1-naphthaldehyde and TMSN₃ in the presence of ZrCl₄, underwent nitrogen extrusion reactions to produce naphtho[1,2-d]isoxazole and 2-hydroxy-1-naphthonitrile in 65 and 15% yields, respectively [12]. The synthesis of 1-substituted naphtho[1,2-d]-isoxazoles is limited to 1-aryl, phenyl or hydroxy substituents. 1-(Aryl or phenyl)naphtho[1,2-d]isoxazoles were prepared by the oxidative cyclisation of 1-[(2-hydroxynaphthalen-1-yl)(aryl or phenyl)methyl]ureas with PhI(OAc)₂ [13]. Transformation of 2-hydroxy-1-naphthonitrile and 1-bromo-4-methoxybenzene into 1-(4-methoxyphenyl)naphtho[1,2-d]isoxazole was achieved by a Barbier−Grignard−type reaction mediated by PPh₃−Mg [14]. A PPh₃−DIAD−triggered Mitsunobu heterocyclization of N,2-dihydroxy-1-naphthamide and diisopropyl azodicarboxylate led to naphtho[1,2-d]isoxazol-1-ol [15].

The first synthesis of parent 7a,8,9,10-tetrahydro-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazin-12-one was accomplished by coupling of phenyl 2-hydroxy-1-naphthoate to 3-(1,3-dioxolan-2-yl)propan-1-amine under microwave irradiation and deacetalization–bicyclization of intermediate amide using SnCl₂·2H₂O [16]Six years later the same parent compound was synthesized by a copper catalyzed intramolecular dehydrogenative (sp³)C−O bond formation in N,N-dibenzyl-2-hydroxy-3,5-dinitrobenzamide [17].

2. Results

As illustrated in Scheme 1 and Table 1, (E)-2-hydroxy-1-naphthaldehyde oxime (2) [18] was prepared, in 96% yield, by heating commercially available 2-hydroxy-1-naphthaldehyde (1) with five equivalents of hydroxylamine hydrochloride in 95% ethanol, along with pyridine, at 60 ^oC for 3 h. Following workup with ethyl acetate and 1 M HCl, the product was obtained without the need for further purification. The oxidation of (E)-2 occurred with 2 equivalents of lead(IV) acetate (LTA) in the presence of 1.5 equivalents of pyrrolidine in anhydrous THF at 0 ^oC for 30 minutes and then at room temperature for 12 h. TLC examination of the dark reaction mixture revealed the consumption of starting material (E)-2 and the appearance of 3 new main spots, together with several faint spots and a polar spot. The workup consisted of adding a 5% sodium bicarbonate solution, followed by extraction with DCM, drying of the solvent, and evaporation, which left a dark oily residue. This residue was subjected to flash column chromatography, yielding (E)-7a,8,9,10-tetrahydro-12H-naphtho[1,2-e]pyrrolo-[2,1-b][1,3]oxazin-12-one oxime (3), 1-(pyrrolidin-1-yl)naphtho[1,2-d]isoxazole (4) and 7a,8,9,10-tetrahydro-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazin-12-one (5) [16,17] in 15, 18 and 10% yield, respectively. This experiment, the workup and purification of products was used for all further experiments (Table 1) with appropriate changes of oxidant, equivalents of pyrrolidine, solvent and time. Thus, to assess the effectiveness of the related reagents, phenyliodine(III) diacetate [PhI(OAc)₂, PIDA], phenyliodine(III) bis(trifluoroacetate) [PhI(OCOCF₃)₂, PIFA], and μ-oxobis[phenyl-(trifluoromethoxy)iodine(III)] {[(PhI(OCOCF₃)]₂O, μ-oxo-bridged PIFA}, the experiment was conducted three times, each time substituting LTA with one of these reagents. Because μ-oxo-bridged PIFA was insoluble in THF, DCM was used instead (Table 1, entry 6. The results showed that the yields of (E)-3, 4 and 5 after the oxidation of (E)-2 with PIDA in THF, were lower than the corresponding yields of (E)-2 with LTA in THF. (E)-2 with PIFA in THF produced even lower yields of (E)-3, 4 and 5. The oxidation of (E)-2 with μ-oxo-bridged PIFA in DCM resulted in 6 faint spots and polar material that moved on TLC as a streak when eluted with methanol. It was thus concluded that attempting to separate the components of this reaction by flash column chromatography or HPLC would not be of any synthetic value. The oxidation of (E)-2 with PIDA or PIFA in DCM followed

the same trend and produced lower yields of (E)-3, 4 and 5 than the corresponding yields of (E)-2 with LTA in THF. Again, the yields of (E)-3, 4 and 5 from (E)-2 and PIFA in DCM are again lower than the respective yields from (E)-2 and PIDA in DCM (Table 1, entries 4 and 5). Better yields, but slighly lower than the first reaction (Table 1, entry 1), were obtained from (E)-2 and PIDA in MeCN (Table 1, entry 7). Since PIDA showed to be the next promising oxidant after LTA, the next three oxidations used 3.0 equivalents of PIDA and 2.5 equivalents of pyrrolidine, in THF, DCM or MeCN (Table 1, entries 8, 9 and 10). The starting material (E)-2 in these reactions was consumed in 8 hours and 3 main spots, together with several faint spots and a polar spot, appeared after TLC examination while workup and the separation of products by flash column chromatography, was similar to the first reaction (Table 1, entry 1). The yields of (E)-3, 4 and 5 from the oxidation of (E)-2 with PIDA, in THF, DCM or MeCN, were again lower than the corresponding yields from the oxidation of (E)-2 by LTA in THF (Table 1, entry 1). Therefore, increasing the equivalents of PIDA and pyrrolidine, as well as conducting the oxidations in three different solvents, did not affect the outcome of the reaction or substantially alter the yields of the three products.

For the formation of products (E)-3, 4 and 5 we propose (Scheme 2) that the oxygen atom of the aldoxime group of (E)-2, displaces acetate anion from LTA to form the organolead intermediate 6, having eliminated acetic acid. From complex 6 lead(II) acetate and acetic acid are eliminated to furnish o-naphthoquinone nitrosomethide 7, which then undergoes Michael addition by pyrrolidine onto the N=O bearing exocyclic alkene carbon atom, to afford nitroso adduct 8. Cyclisation of 8 by a 5-exo-trig addition reaction between hydroxy and nitroso groups forms the intermediate 1-pyrrolidin-1-ylnaphtho[1,2-d]isoxazol-2(1H)-ol 9. On the other hand, a free rotation about the benzylic σ-bond of 8 and reaction of the naphthol OH with LTA leads to organolead intermediate 10. Intramolecular abstraction of the acidic proton of the pyrrolidine group in 10 and elimination of acetic acid, gives intermediate carbanion 11, which cyclises to intermediate naphthopyrrolo-oxazaplumbepine 12, by eliminating acetate ion. Rearrangement of the lead and oxygen atoms in compound 12 affords 12-nitrosonaphthopyrrolooxazine 13 which in the presence of acid tautomerizes to the oxime (E)-3. The oxime is unstable in the presence of LTA and is hydrolized to the ketone 5.

3. Discussion

In our earlier work, the oxidative cyclisation of (E)-2 with LTA in THF, lead to the formation of 4-hydroxynaphtho[1,8-de][1,2]oxazine 14 and naphtho[1,2-d]isoxazole 2-oxide 15. [19]. The latter compound was isolated only once by chance. Thereafter, whenever the reaction was repeated, 14 and spiro dimer 16 were isolated (Scheme 3) [20]. Oxidative peri-cyclization and alkoxylation of (E)-2 to 3a-alkoxynaphtho[1,8-de][1,2]oxazin-4(3aH)-ones 17 was achieved using PhI(OAc)₂ in various aliphatic alcohols. When the alcohol in this reaction was the non-nucleophilic t-BuOH, only oxidative peri-cyclization occurred to give 14. [21]. These reactions have been rationalized by invoking the agency of the peri-orientated o-naphthoquinone nitrosomethide 18 generated from the oxidation of oxime (E)-2. The intriguing structural features reflected on the reactivity profile of this intermediate have been reported [22,23].

At the start of the present work, we repeated the oxidation of (E)-2 with LTA in THF (Scheme 3) but this time adding pyrrolidine as nucleophile (Table 1, entry 1). We anticipated that the in situ generated o-naphthoquinone nitrosomethide 7 (Scheme 2) would function as Michael acceptor towards pyrrolidine and form nitroso intermediate 8 (Scheme 2). The latter is expected to tautomerize to oxime 19, oxidize to o-naphthoquinone nitrosomethide 20 and then undergo 6π-electrocyclization to 21. In the literature there are many examples of 3-substituted benzo[d]isoxazole 2-oxides [24,25]. The same reaction is also expected to produce 14 and 16 (Scheme 3), depending on the efficiency of the competing Michael addition. The use of PIDA instead of LTA in the oxidation of (E)-2 with pyrrolidine (Table 1, entries 2, 4, 7–10), was anticipated to furnish naphthooxazinone 22, based on the reaction that gave 17. Compounds 14, 16, 21 and 22 were absent in all the reactions listed in Table 1.

Products (E)-3, 4 and 5 were characterized using UV–VIS, IR, ¹H and ¹³C NMR spectroscopy and, HRMS spectrometry (see Supplementary Materials for the mentioned spectra) that confirmed their molecular formulae. The UV–VIS spectrum of (E)-3 showed two strong absorptions at 284.6 nm and 339.2 nm, which fall within the absorption range typically observed for unsubstituted naphthalene. In the IR spectrum, the (OH) str. absorption band is not visible in the region 3400–3300 cm⁻¹ probably due to hydrogen bonding, the absorption band at 3063 (w) cm⁻¹ was assigned to aromatic C-H str. and at 2910 (w) to aliphatic C-H str. while the absorption bands at 1618 (m) and 1588 (m) cm⁻¹ were assigned to aromatic C=C str. vibrations. In the ¹H NMR spectrum of product (E)-3 in CDCl₃, the broad singlet at 10.05 ppm represented the proton of the hydroxyl group. In the aromatic region in the range of 8.66–7.25 ppm there are six aromatic protons and at 6.00 ppm the singlet was assigned to the aliphatic proton of the pyrrolidine ring. The remaining three multiplets in the pyrrolidine ring, at 3.20–2.90, 2.38–2.17, and 1.94–1.66 ppm, each integrated for two protons and were assigned to the three methylene groups. The ¹³C NMR spectrum in CDCl₃ showed 15 signals as expected. High-resolution mass spectrometry analysis by ESI confirmed the expected molecular ion at m/z = 255.1125 [M + H]⁺, which was calculated for C₁₅H₁₅N₂O₂⁺ m/z = 255.1128. The ¹H and ¹³C NMR spectroscopic data of compound 5 are in good agreement with the corresponding published data [17]. In the ¹H NMR spectrum of 5 in CDCl₃, the region from 9.15 ppm to 7.14 ppm, showed a total of 6 aromatic protons. The singlet at 5.56 ppm corresponded to the aliphatic proton of the pyrrolidine ring, while the peaks at 4.03 and 3.67 ppm, 2.49 and 2.42–2.34 ppm, and 2.18 and 2.03 ppm each integrated for one proton, with the pairs of peaks assigned to the three methylene groups in the pyrrolidine ring. The ¹³C NMR spectrum in CDCl₃ showed 15 signals that agreed with the number of carbon atoms in the molecule. Furthermore, high-resolution mass spectrometry analysis that was recorded by ESI confirmed the expected molecular ion at m/z = 240.1017 [M + H]⁺, which was calculated for C₁₅H₁₄NO₂⁺ m/z = 240.1019. The ¹H NMR peaks in compound (E)-3 were in a similar ppm range to those in compound 5. Additionally, the peak at 161.45 ppm in the ¹³C NMR spectrum of 5, which was assigned to the carbonyl group, was not observed in the ¹³C NMR spectrum of (E)-3. These observations provide additional support for the proposed structure of (E)-3. The UV–VIS spectrum of compound 4 showed three strong absorptions at 214.4, 233.0 and 249.6 nm. The first two are within the range of the absorptions found in unsubstituted naphthalene [26] and the third is within the range of the absorptions found in substituted isoxazoles [27]. In the IR spectrum, the absorption band at 3056 (w) cm⁻¹ was assigned to aromatic C–H str., and at 2974 (w) and 2874 (w) cm⁻¹ to aliphatic C–H str. while the absorption bands at 1647 (m) and 1618 (m) cm⁻¹ were assigned to aromatic C=C str. vibrations. In the ¹H NMR spectrum of product 4 in CDCl₃, the doublets at 8.39 and 7.90 ppm each integrated for one proton, the multiplet in the range 7.59 ppm to 7.48 ppm integrated for three protons and the triplet at 7.45 ppm integrated for one proton. Thus, the total number of aromatic protons was six. The aliphatic signals in the region 3.82 ppm and 3.71 ppm integrate for four protons and together with the signals in the region 2.15 ppm to 2.04 ppm that also integrate for four protons, together represented the eight protons of the N-substituted pyrrolidine ring. The ¹³C NMR spectrum showed 13 signals. Signals at 47.60 ppm and 25.66 ppm contained two equivalent carbon atoms, each bringing the total number of carbon atoms to 15, as expected. In the ¹H NMR spectrum of parent naphtho[1,2-d]-isoxazole in CDCl₃, there was a singlet at 9.11 ppm that corresponded to the imine proton [9]. This proton was absent in the ¹H NMR spectrum of product 4. This observation excluded compound 22 from being a product since in the related compounds 17 the imine proton appears as a singlet in the region 8.33 ppm to 8.15 ppm. High-resolution mass spectrometry analysis, using ESI, confirmed the expected molecular ion of 4 at m/z = 239.1173 [M + H]⁺, which was calculated for C₁₅H₁₅N₂O⁺ m/z = 239.1178. The calculated m/z = 255.1134 for C₁₅H₁₅N₂O₂⁺ [M + H]⁺ of 21 did not appear in the HRMS spectrum of 4.

Scheme 2 describes the proposed mechanism of the oxidation of (E)-2 to 4, (E)-3 and 5, where an analogy to the intermediacy of cyclic organolead intermediate 12 has been reported by Belostotskaya and co-workers [28] who oxidatively cyclized o-(dimethylaminomethyl)phenol 23 into 1,3-benzoxazine 26 (Scheme 4), via the proposed cyclic organolead intermediate 25.

In the last step of the mechanism outlined in Scheme 2, it was proposed that oxime (E)-3 undergoes hydrolysis to form the ketone 5. The reaction of ketoximes with Koser’s reagent [PhI(OH)OTs] in tetrahydrofuran was reported [29] to afford the corresponding ketones, supporting this hypothesis.

Our expectation from the present research was that the main product of this reaction would be 1-(pyrrolidin-1-yl)naphtho[1,2-d]isoxazole (4), and we had hoped that this would provide a method to introduce nucleophiles in position 1 of naphtho[1,2-d]isoxazole. While there was initial interest in synthesizing a series of 3-substituted naphtho[1,2-d]isoxazole derivatives to explore their biological activities, the low yield of compound 4 and the consistent formation of products (E)-3 and 5 in all reaction trials, ultimately reduced enthusiasm for the project.

4. Materials and Methods

All reactions were carried out under a N₂ atmosphere. Solvents and reagents were used as received from the manufacturers (Aldrich, Acros and Alfa Aesar) except for DCM, EtOAc and hexane that were purified and dried according to recommended procedures. Organic solutions were concentrated by rotary evaporation at 23–40 °C under reduced pressure (15 Torr). Melting points were taken on a Büchi 510 apparatus (Büchi Labortechnik AG, Switzerland). The IR spectra were acquired on an Agilent Cary 630 FTIR spectrophotometer (Agilent Technologies) as a solid and reported in wave numbers (cm⁻¹). The UV spectrum was recorded using a Jasco V-630 UV-Vis spectrophotometer (Jasco Europe s.r.l., Cremella, Italy). The samples were measured in a 1 cm quartz cell at room temperature in MeCN with concentrations of 9 × 10^-2mM and 9 × 10^-5mM for (E)-3, 25 × 10^-6mM for 4 and, 1 × 10^-1mM and 1 × 10^-2mM for 5. Samples for ¹H and ¹³C NMR experiments were dissolved in dry DMSO-d₆ or CDCl₃ and were recorded on a Brüker Avance 400 MHz spectrometer (Brüker BioSpin GmbH, Rheinstetten, Germany). The chemical shifts (δ) were reported in ppm and referenced to residual solvent signals. Coupling constants (J) were given in Hz. The high-resolution ESI mass spectrum was measured on a ThermoFisher Scientific Orbitrap XL system (Thermo Fisher Scientific, Waltham, MA, USA). Analytical thin layer chromatography (TLC) was performed with Merck 70–230-mesh silica gel precoated TLC aluminium plates. TLC plates were observed under UV light at 254 and 365 nm. Preparative flash chromatography was carried out using Merck 9385 silica gel.

4.1. (E)-7a,8,9,10-Tetrahydro-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazin-12-one oxime (3), 1-(pyrrolidin-1-yl)naphtho[1,2-d]isoxazole (4) and 7a,8,9,10-Tetrahydro-12H-naphtho[1,2-e]pyrrolo-[2,1-b][1,3]oxazin-12-one (5)

To a stirred solution of (E)-2-hydroxy-1-naphthaldehyde oxime 2 (200 mg, 1.068 mmol, 1 equiv) in dry THF (10 mL) at 0 °C, under a nitrogen atmosphere, pyrrolidine (113 mg, 1,6 mmol, 1.5 equiv) was added followed by a slow addition of Pb(OAc)₄ (940 mg, 2.136 mmol, 2 equiv). The reaction was stirred at 0 °C for 30 min and then at room temperature for 12 h. TLC examination revealed the absence of the starting material spot and the presence of three new spots (visualized under a UV lamp). A 5% solution of NaHCO₃ (20 mL) was added dropwise to bring the pH = 7–8. The THF/H₂O reaction mixture was extracted with DCM (3 × 10 mL), the combined organic extracts were washed with brine (20 mL), dried over anhydrous Na₂SO₄ and the solvent removed under reduced pressure. The acquired brown oil was purified by flash column chromatography (10% EtOAc in hexane) to give (E)-3 (42 mg, 15% yield) as a brown solid, mp: 91–93 ^oC, 4 (43 mg, 18% yield) as a yellow solid, mp: 65–67 ^oC and 5 (26 mg, 10% yield) as a light brown oil.

4.1.1. (E)-7a,8,9,10-Tetrahydro-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazin-12-one oxime (3)

R_f = 0.35 (EtOAc/hexane, 20:80); UV-VIS (MeCN), nm (9 × 10^-2mM): λ_max 284.6 (log ε 12264), 339.2 (log ε 6318), nm (9 × 10^-5mM): λ_max 274.2 nm (log ε = 1604444); FTIR (solid) cm⁻¹: 3063 (w), 2910 (m), 1618 (m), 1588 (m); ¹H NMR (400 MHz, CDCl₃) δ: 10.05 (s, 1H), 8.66 (d, J = 8.7 Hz, 1H), 7.85 (d, J = 8.9 Hz, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.25 (d, J = 9.0 Hz, 1H), 6.00 (s, 1H), 3.20–2.90 (m, 2H), 2.38–2.17 (m, 2H), 1.94–1.66 (m, 2H); ¹³C NMR (100.6 MHz, CDCl₃) δ: 157.30, 133.37, 131.73, 128.80, 128.64, 127.60, 124.54, 123.66, 118.59, 102.36, 98.41, 52.62, 33.58, 29.72, 23.24; HRMS (ESI): m/z [M + H]⁺ calcd. for C₁₅H₁₅N₂O₂⁺: 255.1128. Found: 255.1125.

4.1.2. 1-(Pyrrolidin-1-yl)naphtho[1,2-d]isoxazole (4).

R_f = 0.2 (EtOAc/hexane, 20:80); UV-VIS (MeCN), nm (25 × 10^-6mM): λ_max 214.4 (log ε = 29368), 233.0 (log ε = 21404), 249.6 (log ε = 22156), 289.4 (log ε = 4246), 310.6 (log ε = 4936), 338.8 (log ε = 7152); FTIR (solid) cm⁻¹: 3056 (w), 2974 (w), 2874 (w), 1647 (m), 1618 (s); ¹H NMR (400 MHz, CDCl₃) δ: 8.39 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.59–7.48 (m, 3H), 7.45 (t, J = 7.5 Hz, 1H), 3.82–3.71 (m, 4H), 2.15–2.04 (m, 4H); ¹³C NMR (100.6 MHz, CDCl₃) δ: 161.19, 144.99, 138.62, 131.09, 128.33, 125.50, 124.89, 124.42, 122.33, 120.25, 109.69, 47.60 (2C), 25.66 (2C). HRMS (ESI): m/z [M + H]⁺ calcd. for C₁₅H₁₅N₂O⁺: 239.1178. Found: 239.1173.

4.1.3. 7a,8,9,10-Tetrahydro-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazin-12-one (5).

R_f = 0.1 (EtOAc/hexane, 20:80); UV-VIS (MeCN), nm (1 × 10^-1mM): λ_max 276.2 (log ε = 3201), 289.2 (log ε = 3628), 300.6 (log ε = 4110), 341.4 (log ε = 3399), 356.6 (log ε = 2474), 390.8 (log ε = 639), 409.8 (log ε = 521), nm (1 × 10^-2mM): λ_max 212.0 (log ε = 55450), 224.2 (log ε = 56120), 251.2 (log ε = 38180), FTIR (solid) cm⁻¹: 3063 (w), 2910 (m), 1618 (m), 1588 (m); ¹H NMR (400 MHz, CDCl₃) δ: 9.15 (d, J = 8.6 Hz, 1H), 7.91 (d, J = 8.9 Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.67–7.59 (m, 1H), 7.46 (t, J = 7.5 Hz, 1H), 7.14 (d, J = 8.9 Hz, 1H), 5.56 (dd, J = 6.0, 4.4 Hz, 1H), 4.03 (dt, J = 13.2, 6.8 Hz, 1H), 3.67 (dt, J = 12.3, 6.8 Hz, 1H), 2.49 (dt, J = 13.3, 6.7 Hz, 1H), 2.42–2.34 (m, 1H), 2.18 (dt, J = 13.4, 6.8 Hz, 1H), 2.03 (td, J = 13.1, 6.5 Hz, 1H); ¹³C NMR (100.6 MHz, CDCl₃) δ: 161.45, 157.69, 134.86, 131.79, 130.09, 128.35, 128.25, 126.08, 124.84, 116.96, 88.12, 45.07, 32.15, 29.70, 22.00 (spectroscopic data are in agreement with those reported in the literature [17]. HRMS (ESI): m/z [M + H]⁺ calcd. for C₁₅H₁₄NO₂⁺: 240.1019. Found: 240.1017.