Bismuth(III) Chloride Catalyzed Intramolecular Hetero-Diels–Alder Reaction: Access to cis-Fused Angular Hexahydrobenzo[c]acridines

Abstract

New polycyclic hexahydrobenzo[c]acridines were synthesized in excellent yields by intramolecular [4+2]-cycloaddition reactions of aldimines derived from aromatic amines and 2-(4-methylpent-3-en-1-yl)benzaldehyde in acetonitrile in the presence of 10 mol% of bismuth(III) chloride. The reaction is highly diastereoselective, giving cis-fused benzoacridine derivatives preferentially.

Key words

hetero-Diels–Alder reactions - catalysis - heterocycles - polycycles - aldimines - aldehydes

The intramolecular hetero-Diels–Alder reaction[1] [2] has become an attractive tool for the synthesis of complex molecular structures. Angularly fused polycyclic nitrogen heterocycles[3] are of great importance to chemists and biologists because of the significant role played by such compounds in biological systems and in medicinal chemistry. Heterocyclic systems containing the hexahydrobenzo[a]acridine skeleton can be prepared by cascade heterocyclization of cyclic diketones with aromatic amines and vanillyl esters.[4] Benzoacridine derivatives have been reported to possess a significant inhibitory effect on the growth of KB human papilloma cells,[5] an activity that is creating interest in further studies on such derivatives. To the best of our knowledge, there have been no reported syntheses of angularly fused hexahydrobenzoacridine derivatives from 2-(4-methylpent-3-en-1-yl)benzaldehyde (1)[6] and aromatic amines. As a continuation of our work on [4+2] cycloaddition chemistry,[7] and on the basis of a report in the literature,[8] we have developed a novel synthesis of angularly fused benzoacridine derivatives by means of the intramolecular hetero-Diels–Alder reaction of 2-(4-methylpent-3-en-1-yl)benzaldehyde with aromatic amines in the presence of bismuth(III) chloride. Aldehyde 1 was prepared in 88% yield from 2-methylbenzaldehyde and 1-bromo-3-methylbut-2-ene (prenyl bromide) in the presence of N,N,N′-trimethyl­ethane-1,2-diamine[6] (Scheme [1]).

The use of bismuth trichloride in the cyclization of aldehyde 1 with amines has several advantages. Bismuth is the least toxic of the heavy elements[9a] [b] and the biochemistry,[9c] toxicology,[9d] and environmental effects[9e] of bismuth compounds have been reviewed. Moreover, bismuth compounds are employed as catalysts in industry for the manufacture of acrolein and acrylonitrile, and they are also used in pharmaceutical products.

Scheme 1 Preparation of 2-(4-methylpent-3-en-1-yl)benzaldehyde (1)

Scheme 2 Preparation of 7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3a)

Having prepared aldehyde 1, we examined its intramolecular [4+2]-cycloaddition reactions. Initially, we studied the reaction of aldehyde 1 with aniline (2a) in the presence of 10 mol% bismuth(III) chloride in acetonitrile at 85 °C, and we obtained 7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3a) in 82% yield (Scheme [2]). The reaction was complete in one hour, as indicated by thin-layer chromatography. The reaction proceeds by generation of an imine that undergoes an intramolecular hetero-Diels–Alder reaction to give the product 3a as a mixture of cis- and trans-diastereomers with the former as the predominant product. The ratio of the cis- and trans-isomers of 3a was determined by NMR spectroscopic studies on the crude product. In compound 3a, the H-6a proton appears as a doublet of triplets at δ = 1.83. This is the result of coupling of the H-6a proton with the H-6′ proton, resulting in a doublet with a large J value (J _6a,6′ = 12.3 Hz) that is split into a triplet with a small J value (3.4 Hz) by coupling with the equatorial H-12a and H-6 protons. This corresponds to a cis-fusion at the junction. The doublet for the H-12a proton appears at δ = 4.65 with a small J value as a result of vicinal coupling with an equatorial H-6a proton (J _12a,6a = 3.2 Hz). The cis-configuration of H-6a and H-12a in compound 3 was confirmed by the strong NOE peaks. Confirmation of the cis-fusion of 3a was also obtained by direct comparison with data reported in the literature,[7b] [d] [f] in addition to the ¹H NMR spectral data.

Table 1 Synthesis of Angular Hexahydrobenzo[c]acridines 3a–k

Entry	R1	R2	R3	R4	Producta	Yieldb (%)	cis/trans c
1	H	H	H	H	3a	82	96:4
2	H	H	Me	H	3b	80	95:5
3	H	H	OMe	H	3c	85	96:4
4	Cl	H	H	H	3d	82	95:5
5	H	H	F	H	3e	75	96:4
6	OH	H	H	H	3f	77	95:5
7	H	H	NO2	H	3g	74	93:7
8	Br	H	H	Br	3h	86	96:4
9	H	Br	H	Br	3i	82	93:7
10	CO2H	H	OMe	H	3j	87	97:3
11	H	OMe	OMe	OMe	3k	80	94:6

^a All products were characterized by NMR and IR spectroscopy, and mass spectrometry.

^b Yield of pure product after chromatography.

^c Ratio determined by ¹H NMR spectroscopy on crude product.

In an effort to demonstrate the scope of the bismuth(III) chloride-catalyzed hetero-Diels–Alder reaction, we examined the reactions of aldehyde 1 with several anilines 2b–k bearing various substituents (Table [1]). Amines bearing electron-donating groups and those bearing electron-withdrawing groups both gave the corresponding products 3 in high yields under similar reaction conditions to those used for aniline (2a); the substituents had no obvious effect on the yield or the reaction time under optimized conditions. In all cases, the cis-annulated products were formed predominantly. The products were characterized by means of IR, ¹H and ¹³C NMR, and mass spectroscopy. Acetonitrile was selected as the optimal solvent, as it gave better results than other solvents tested such as methanol, tetrahydrofuran, diethyl ether, dichloromethane, or 1,2-dichloroethane.

Mechanistically, the reaction proceeds through formation of an imine from the aromatic amine and 2-(4-methylpent-3-en-1-yl)benzaldehyde (1). The imine then undergoes a Lewis acid induced intramolecular hetero-Diels–Alder reaction to give the hexahydrobenzo[c]acridine (Scheme [3]).

Scheme 3 A plausible reaction mechanism

In conclusion, we have demonstrated a convenient synthesis of cis-fused hexahydrobenzo[c]acridines derivatives in good yields in a one-pot operation using bismuth(III) chloride. The advantages of the present protocol are mild conditions, short reaction times, and the use of a soft Lewis acid catalyst that is commercially available. The method is therefore highly practical and might find wide applicability in organic synthesis.

All reagents and catalysts were purchased from Sigma-Aldrich. Reactions were conducted under N₂ in anhydrous solvents such as THF or MeCN. All reactions were monitored by TLC on Merck 60 F-254 silica gel plates visualized under UV radiation. Hexanes (bp 60–80 °C) and EtOAc were used for silica gel column chromatography. Yields refer to chromatographically and spectroscopically (¹H and ¹³C NMR) homogeneous materials. Air-sensitive reagents were transferred by syringe. Evaporation of solvents was performed at reduced pressure on a Buchi rotary evaporator. ¹H and ¹³C NMR spectra of samples in CDCl₃ were recorded on Bruker UXNMR FT-300 MHz (Avance) spectrometers with TMS as an internal standard. Mass spectra were recorded on a Finnigan MAT 1020B or a Micromass VG 70–70 H spectrometer operated at 70 eV with a direct inlet system. Column chromatography was performed on silica gel (60–20 mesh; ACME Chemicals, Mumbai).

2-(4-Methylpent-3-en-1-yl)benzaldehyde (1)[6]

A solution of Me₂N(CH₂)₂NHMe (1.1 mL, 9.8 mmol, 1.1 equiv) in THF (20 mL) at –20 °C was sequentially treated with a 1.6 M solution of BuLi in hexanes (5.89 mL, 9.43 mmol, 1.05 equiv) and 2-MeC₆H₄CHO (1.08 g, 8.98 mmol). After 15 min, a further 3 equivalents of BuLi were added at –20 °C, Me₂C=CCH₂Br (5.4 mL, 35.95 mmol, 4 equiv) was added at –78 °C, and the mixture was stirred for 30 min. The resulting mixture was then poured into cold sat. aq NH₄Cl (10 mL) and extracted with EtOAc (3 × 20 mL). The extracts were combined, washed with brine (2 × 10 mL), dried (Na₂SO₄), and concentrated under reduced pressure. The crude product was purified by flash column chromatography [silica gel, hexane–EtOAc (15:1)] to give a colorless oil; yield: 1.48 g (88%).

IR (neat): 3447, 2961, 2927, 2860, 1696, 1600, 1450, 1207, 757 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 10.27 (s, 1 H), 7.83 (dd, J = 7.7, 1.3 Hz, 1 H), 7.50 (td, J = 7.6, 1.3 Hz, 1 H), 7.36 (td, J = 7.6, 1.0 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 1 H), 5.20–5.15 (m, 1 H), 3.08–3.01 (m, 2 H), 2.30 (qt, J = 15.1, 7.5 Hz, 2 H), 1.66 (s, 3 H), 1.45 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 191.9, 145.0, 133.6 (2 C), 131.1, 130.9, 126.4, 122.7, 32.3, 30.5, 25.6, 17.4. .

ESI-MS: m/z = 211 [M⁺ + Na].

7,7-Dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridines 3a–k; General Procedure

BiCl₃ (10 mol%) was added to a mixture of the appropriate aromatic amine 2a–k (1 mmol) and aldehyde 1 (1.1 mmol) in anhyd MeCN (5 mL), and the mixture was refluxed at 85 °C for 1 h. When the reaction was complete (TLC), the mixture was filtered through Celite. The filtrate was extracted with EtOAc (3 × 20 mL), and the extracts were combined, washed with brine (2 × 10 mL), dried (Na₂SO₄), and concentrated. The crude product was purified by chromatography [silica gel, hexanes–EtOAc (16:1)].

7,7-Dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3a)

Pale yellow viscous liquid; yield: 251 mg (82%).

IR (neat): 3445, 3062, 2961, 2926, 1603, 1562, 1474, 1216, 758 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.40–7.30 (m, 5 H), 6.67–6.61 (m, 1 H), 6.37 (d, J = 7.7 Hz, 1 H), 5.69 (dt, J = 7.3, 1.3 Hz, 1 H), 4.65 (d, J = 3.2 Hz, 1 H), 4.29 (s, 1 H), 2.93–2.87 (m, 1 H), 2.82 (dd, J = 12.0, 6.1 Hz, 1 H), 2.68–2.64 (m, 1 H), 1.83 (dt, J = 12.3, 3.4 Hz, 1 H), 1.70–1.65 (m, 1 H), 1.45 (s, 3 H), 1.36 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 141.4, 130.7, 129.2, 128.2, 128.1, 127.9, 127.6, 126.7, 126.6, 124.9, 117.3, 112.6, 45.8, 40.5, 32.3, 28.3, 25.6, 25.0, 17.6.

ESI-MS: m/z = 265 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₁₉H₂₂N: 264.1752; found: 264.1761.

7,7,9-Trimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3b)

Pale yellow viscous liquid; yield: 221 mg (80%).

IR (neat): 3449, 2924, 2854, 1634, 1459, 1217, 765 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.42 (d, J = 7.6 Hz, 1 H), 7.38–7.28 (m, 1 H), 7.20 (dt, J = 7.9, 0.6 Hz, 1 H), 7.17–7.14 (m, 1 H), 7.11 (d, J = 1.3 Hz, 1 H), 6.85–6.83 (m, 1 H), 6.59 (d, J = 7.9 Hz, 1 H), 4.30 (d, J = 10.3 Hz, 1 H), 4.22–4.11 (br s, 1 H), 2.93–2.89 (m, 1 H), 2.27 (s, 3 H), 2.08–2.03 (m, 1 H), 1.79–1.73 (m, 1 H), 1.59–1.50 (m, 2 H), 1.40 (s, 3 H), 1.23 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 137.7, 135.7, 132.2, 130.5, 129.1, 128.3, 128.2, 127.3, 126.6, 126.3, 125.7, 116.0, 51.4, 46.9, 35.9, 30.9, 28.3, 27.9, 21.9, 17.6.

ESI-MS: m/z = 278 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₂₀H₂₄N: 278.1908; found: 278.1902.

9-Methoxy-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3c)

Colorless viscous liquid; yield: 249 mg (85%).

IR (neat): 3423, 3063, 2959, 2933, 1612, 1512, 1474, 1228, 1037, 819 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.38–7.13 (m, 4 H), 6.84–6.77 (m, 1 H), 6.64–6.55 (m, 1 H), 6.34 (d, J = 8.3 Hz, 1 H), 4.60 (d, J = 3.0 Hz, 1 H), 4.24 (s, 1 H), 3.75 (s, 3 H), 2.91–2.79 (m, 1 H), 2.68 (dd, J = 15.1, 7.5 Hz, 1 H), 1.87–1.78 (m, 1 H), 1.71–1.46 (m, 2 H), 1.43 (m, 3 H), 1.37 (m, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 159.4, 141.0, 137.9, 130.4, 129.3, 128.1, 126.6, 126.5, 126.0, 114.8, 111.7, 111.3, 70.8, 55.7, 55.3, 40.8, 28.3, 25.6, 25.1, 17.6. 6.

ESI-MS: m/z = 294 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₂₀H₂₄NO: 294.1857; found: 294.1859.

11-Chloro-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3d)

Pale yellow viscous liquid; yield: 243 mg (82%).

IR (neat): 3436, 3063, 2961, 2929, 2869, 1696, 1496, 1303, 1240, 771, 731 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.48 (d, J = 7.7 Hz, 1 H), 7.33–7.27 (m, 1 H), 7.24–7.20 (m, 2 H), 7.17 (d, J = 7.5 Hz, 1 H), 7.12 (dd, J = 7.7, 1.2 Hz, 1 H), 6.6 (t, J = 7.7 Hz, 1 H), 5.01–4.96 (br s, 1 H), 4.36 (d, J = 10.5 Hz, 1 H), 2.73 (dd, J = 7.7, 2.8 Hz, 2 H), 2.09–2.03 (m, 1 H), 1.80–1.74 (m, 1 H), 1.62–1.55 (m, 1 H), 1.41 (s, 3 H), 1.23 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 136.8, 131.2, 129.2, 128.1, 126.8, 126.5, 125.5 (2 C), 125.0, 123.5, 120.8, 117.3, 51.0, 46.0, 30.3, 27.6, 26.9, 21.7, 17.8.

ESI-MS: m/z = 298 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₁₉H₂₁ClN: 298.1362; found: 298.1354.

9-Fluoro-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3e)

Colorless viscous liquid; yield: 210 mg (75%).

IR (neat): 3420, 2925, 2854, 1615, 1470, 1275, 1187, 769 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.44 (d, J = 7.5 Hz, 1 H), 7.27–7.14 (m, 3 H), 7.00 (dd, J = 10.6, 3.0 Hz, 1 H), 6.75 (dt, J = 8.3, 2.2 Hz, 1 H), 6.61 (dd, J = 8.3, 5.3 Hz, 1 H), 4.29 (d, J = 10.6 Hz, 1 H), 4.29–4.26 (br s, 1 H), 2.92 (dd, J = 8.3, 3.0 Hz, 2 H), 2.09–2.01 (m, 1 H), 1.77–1.65 (m, 1 H), 1.62–1.53 (m, 1 H), 1.39 (s, 3 H), 1.23 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 141.2, 139.3, 130.7, 129.8, 129.7, 128.2, 126.7, 126.6, 114.2, 114.0, 112.3, 112.1, 70.5, 40.9, 29.7, 28.3, 25.5, 25.0, 17.6.

ESI-MS: m/z = 282 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₁₉H₂₁FN: 282.1658; found: 282.1668.

7,7-Dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridin-11-ol (3f)

Colorless liquid; yield: 214 mg (77%).

IR (neat): 3422, 3066, 2966, 2928, 1617, 1452, 1216, 751 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.42–7.30 (m, 2 H), 7.28–7.19 (m, 3 H), 7.19–7.12 (m, 1 H), 6.95–6.91 (m, 1 H), 6.70–6.42 (br s, 1 H), 4.81–4.46 (m, 2 H), 2.91 (dd, J = 17.0, 5.1 Hz, 1 H), 2.86–2.79 (m, 1 H), 2.32–1.99 (m, 1 H), 1.88–1.81 (m, 1 H), 1.74–1.59 (m, 1 H), 1.40 (s, 3 H), 1.36 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 137.2, 130.9, 129.3, 129.1, 129.0, 128.4, 127.7, 126.6, 126.5, 126.0, 116.0, 113.1, 71.4, 40.7, 29.3, 28.2, 25.5, 25.1, 17.4.

ESI-MS: m/z = 280 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₁₉H₂₂NO: 280.1701; found: 282.1707.

7,7-Dimethyl-9-nitro-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3g)

Yellow viscous liquid; yield: 228 mg (74%).

IR (KBr): 3402, 2953, 2865, 1603, 1510, 1318, 1279, 737 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 8.12 (d, J = 2.3 Hz, 1 H), 7.91 (dt, J = 9.1, 2.3 Hz, 1 H), 7.33–7.23 (m, 4 H), 6.30 (d, J = 9.1 Hz, 1 H), 4.74 (d, J = 3.8 Hz, 1 H), 4.55–4.50 (br s, 1 H), 2.98–2.91 (m, 1 H), 2.89–2.84 (m, 1 H), 1.91–1.79 (m, 1 H), 1.78–1.61 (m, 1 H), 1.64–1.56 (m, 1 H), 1.53 (s, 3 H), 1.35 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 147.6, 137.6, 136.8, 136.2, 129.3, 128.8, 128.3, 126.7, 126.5, 124.2, 123.0, 111.8, 50.2, 41.9, 35.4, 32.4, 29.0, 25.4, 19.2.

ESI-MS: m/z = 309 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₁₉H₂₁N₂O₂: 309.1603; found: 309.1595.

8,11-Dibromo-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3h)

Brown viscous liquid; yield: 359 mg (86%).

IR (neat): 3414, 3015, 2960, 2927, 1577, 1483, 1442, 1292, 742 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.33–7.22 (m, 3 H), 7.18 (d, J = 7.3 Hz, 1 H), 7.04 (d, J = 8.4 Hz, 1 H), 6.75 (d, J = 8.4 Hz, 1 H), 4.60 (d, J = 2.7 Hz, 1 H), 4.53–4.47 (br s, 1 H), 2.95–2.90 (m, 1 H), 2.83 (dd, J = 11.7, 6.2 Hz, 1 H), 1.97–1.90 (m, 1 H), 1.80 (s, 3 H), 1.69–1.64 (m, 1 H), 1.58 (dd, J = 12.6, 5.9 Hz, 1 H), 1.53 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 41.5, 137.1, 136.9, 130.6, 129.2, 129.0, 128.1, 127.2, 126.3, 123.6, 122.2, 107.7, 49.8, 46.8, 37.9, 29.8, 29.3, 27.4, 18.9.

ESI-MS: m/z = 422 [M + 2]⁺, 424 [M + 4]⁺.

HRMS: m/z [M + H]⁺ calcd for C₁₉H₂₀Br₂N: 419.9962; found: 419.9954.

8,10-Dibromo-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3i)

Brown viscous liquid; yield: 342 mg (82%).

IR (neat): 3412, 3015, 2961, 2927, 1577, 1443, 1293, 755 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.28–7.25 (m, 1 H), 7.24–7.22 (m, 2 H), 7.17 (d, J = 7.3 Hz, 1 H), 7.00 (d, J = 2.0 Hz, 1 H), 6.45 (d, J = 2.0 Hz, 1 H), 4.54 (d, J = 2.3 Hz, 1 H), 3.92–3.86 (br s, 1 H), 2.95–2.90 (m, 1 H), 2.83 (dd, J = 11.7, 6.8 Hz, 1 H), 1.96–1.90 (m, 1 H), 1.77 (s, 3 H), 1.63–1.54 (m, 2 H), 1.49 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 145.6, 137.0, 136.2, 130.9, 129.2, 128.9, 128.1, 126.3, 125.4, 119.9, 115.5, 114.0, 49.3, 46.5, 37.2, 29.3, 29.6, 27.6, 19.0.

ESI-MS: m/z = 422 [M + 2]⁺, 424 [M + 4]⁺.

HRMS: m/z [M + H]⁺ calcd for C₁₉H₂₀Br₂N: 419.9962; found: 419.9976.

9-Methoxy-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine-11-carboxylic Acid (3j)

Colorless gummy liquid; yield: 293 mg (87%).

IR (KBr): 3450, 2960, 1652, 1583, 1497, 1426, 1217 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.43 (d, J = 3.0 Hz, 1 H), 7.34–7.12 (m, 3 H), 7.08–7.01 (m, 1 H), 6.59 (d, J = 9.0 Hz, 1 H), 4.75 (d, J = 3.0 Hz, 1 H), 4.42 (s, 1 H), 3.77 (s, 3 H), 2.92–2.77 (m, 1 H), 2.73–2.61 (m, 1 H), 2.31–2.00 (m, 1 H), 1.75–1.57 (m, 2 H), 1.46 (s, 3 H), 1.34 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 173.2, 149.3, 146.9, 135.8, 129.3, 129.1, 127.6, 127.2, 126.1, 124.8, 122.2, 114.4, 113.3, 55.8, 49.4, 44.9, 32.4, 31.8, 30.5, 22.5, 19.3.

ESI-MS: m/z = 338 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₂₁H₂₄NO₃: 338.1756; found: 338.1761.

8,9,10-Trimethoxy-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3k)

Colorless gummy liquid; yield: 282 mg (80%).

IR (neat): 3387, 2962, 2932, 1605, 1481, 1456, 1106, 752 cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.25–7.15 (m, 4 H), 5.76 (s, 1 H), 4.49 (d, J = 2.6 Hz, 1 H), 3.92 (s, 3 H), 3.77 (s, 3 H), 3.72 (s, 3 H), 3.59–3.53 (br s, 1 H), 2.98–2.91 (m, 1 H), 2.87–2.79 (m, 1 H), 1.96–1.90 (m, 1 H), 1.73–1.64 (m, 1 H), 1.57 (m, 4 H), 1.42 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 156.7, 154.4, 152.0, 138.1, 137.2, 132.9, 129.1, 128.9 (2C), 127.7, 125.9, 93.1, 60.6, 60.5, 55.5, 50.1, 46.1, 32.3, 29.4, 27.1, 24.6, 19.1.

ESI-MS: m/z = 354 [M⁺ + H].

HRMS: m/z [M + H]⁺ calcd for C₂₂H₂₈NO₃: 354.2069; found: 354.2058.

Acknowledgment

K.S. thanks CSIR, New Delhi, for the award of a fellowship.

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For reviews, see:
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