Synthesis of anti-2,3-dihydro-1,2,3-trisubstituted-1H-naphth [1,2-e][1,3]oxazine derivatives via multicomponent approach

Abstract

A series of anti-2,3-dihydro-1,2,3-trisubstituted-1H-naphth [1,2-e][1,3]oxazine derivatives 6 were exclusively obtained in high yields for the first time through multicomponent reactions (MCRs) of 2-naphthol, aromatic aldehydes and electron rich primary amines in ethanol at room temperature using CCl₃COOH as catalyst. The same reaction could be conducted effectively in solvent-free medium at 100 °C. The stereochemistry of the two hydrogens connected to C-2 and C-4 (1,3) positions of the oxazine ring are identified as anti-orientation by single crystal XRD, COSY and NOESY analysis.

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Introduction

Multicomponent synthesis of fused 1,3-oxazine derivatives have emerged as a challenging structure development in organic chemistry in the context of modern drug discovery.¹ Various oxazine derivatives have been shown to exhibit wide a spectrum of pharmacological activities such as antitumor, positive alloasteric modulation, antimicrobial, anti-HIV and anti-malarial agent.² Substituted naphthoxazine derivatives are used for the therapy of Parkinson disease.³ Several one pot synthesis of fused 1,3-oxazines have previously been reported which included pyrrolo/pyrido[2,1-a]benzoxazin-ones and pyrrolo/pyrido[2,1-a] quinazolinones,^4a pyrido[2,3-e][1,3]oxazine,^4b benzoxazine derivatives,^4c substituted imidazo[2,1-b][1,3]oxazines derivatives,^5a,b substituted naphth-[1,2-e][1,3]oxazines etc.^6–8 The synthesis of mono substituted naphth-[1,3]oxazine was first disclosed by Bruke et al. and then by Shingare et al. in PEG-400 by stirring a mixture of 2-naphthol, formaldehyde and substituted aniline (Fig. 1, 1).^6a,b It has been observed that the preparation of 1,3-disubstituted naphth-[1,2-e] [1,3]oxazine is only limited to the use of 1-or 2-naphthol with various aryl and heteroaryl aldehydes in dry methanolic ammonia solution at room temperature with longer reaction time (24–48 h) and lower yields (Fig. 1, 2 and 4).^7a Later on, the use of ammonium acetate reduced the reaction time in solvent-free medium using thermal and microwave energies.^7b Substituent effects in the ring-chain tautomerism of 1,3-disubstituted naphtho-[1,3]-oxazine derivatives in solution were extensively studied by Fulop and his group (Fig. 1, 2–4).^7c,d Recently a copper catalyzed regioselective intramolecular oxidative α-functionalization of tertiary aminonaphthol were designed by Maycock et al. for the synthesis of some fused trisubstituted-naphtho[1,3]oxazine derivatives in p-xylene at 130 °C within 2–7 hours.^8a A low valent titanium systems were also developed for the chemoselective conversion of 1,3-diaryl-2,3-dihydro-1H-naphtho[1,2-e][1,3]-oxazines to naphtho[1,2-e][1,3]oxazine-2(3H)-carbonyl chloride and naphtho[1,2-e][1,3]oxazine-3-one in THF under reflux.^8b To the best of our knowledge, there is no report for the multicomponent synthesis of 1,2,3-trisubstituted-naphth-[1,3]oxazine 6 using acid catalyst in solution as well as solvent-free medium. In literature only few compounds of 1,2,3 trisubstituted-naphth-[1,2-e][1,3]oxazines were known without studying the orientation of H-2 and H-4 protons in the oxazine ring. Cimarelli et al. identified the two derivatives of 1,2,3-trisubstituted-naphth[1,3]oxazines (19–28% yields) as side products during the stereoselective synthesis of aminoalkylnaphthol at 60 °C after 12–24 hours reaction.^9a Li et al. reported the synthesis of 2-butyl-1,3-dihydro-1H-naphth-[1,2-e] [1,3]oxazine by the MCRs of 2-naphthol, butylamine and benzaldehyde in ethanol for 6 days stirring at room temperature.^9b These studies revealed that there is a lot of scope for generation of combinatorial library of novel 1,2,3-trisubstituted naphth-[1,3]oxazines using multi-component approach.

Fig. 1 Mono-substituted oxazine 1 and tautomerism of 1,3-disubstituted-naphth-[1,3]oxazines 2–4.

Herein, we described an efficient trichloroacetic acid catalyzed three component selective synthesis of anti-1-2,3-trisubstituted-naphth-[1,3]oxazine diastereomer 6 in solution and under solvent-free medium (Scheme 1).

Scheme 1 Multicomponent synthesis of anti-1,2,3-trisubstituted-naphth-[1,3]oxazine diastereomer.

Results and discussion

The preliminary works involved with the optimization of condition for a typical reaction of 2-naphthol (1 mmol), benzaldehyde (2 mmol) and aniline (1 mmol) in presence of three acid catalysts such as acetic acid, trichloroacetic acid and trifluroacetic acid at 25 °C in CHCl₃. We also studied the catalytic activity of these acids for the same reaction under solvent-free medium. Table 1 distinctly represented the selective formation of anti-product 6a with the three catalysts in all conditions out of the two possible diastereomers 6a and 7a. In anti-product, the oxazine moiety suffers from less steric effect of the three phenyl groups.

Table 1 Optimization of the reaction with acid catalysts

Entry	Catalyst	Amt. (mol%)	Time (min)	Conv. 6a^a (%)
a Isolated yields.b Reaction in CHCl3 at room temperature.c Reaction in solvent-free medium at 100 °C.d Reaction in CHCl3 at 0 °C.e Reaction in solvent-free medium at 80 °C.f Product decomposed.
1	CH3COOH	25	60^b/40^c	75/82
2	CCl3COOH	25	30^b/20^c	87/92
3	CF3COOH	25	30^b/20^c	93/30^f
4	CH3COOH	10	120^b	40
5	CCl3COOH	10	40^b	75
6	CF3COOH	10	25^b	80
7	CCl3COOH	25	30^d/30^e	85/75
8	No catalyst	—	12 h^b/4 h^c	40/50

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The syn-product 7a will be unstable from the above mentioned steric effects. The optimization results identified 25 mol% of CCl₃COOH as the suitable catalyst to complete the reaction within short time in solution at 25 °C and 100 °C in absence of solvent (Table 1, entries 2). Decreasing reaction temperature had reduced the yield of product under solvent-free condition with the best catalyst as compared to solution at 0 °C (entry 7). The higher acidity of CF₃COOH destabilized the oxazine ring at high temperature, but it gave excellent result in chloroform under mild condition (entry 3). The lower acidity of acetic acid increased the reaction time to give good yield of product (entry 1). Without catalyst, the reactions were uncompleted for longer reaction time (entry 8). Again, use of stronger acids like H₂SO₄ and HCl reduced the anti-product selectivity and generated various side products in ethanol at ambient temperature.

The effects of solvents were also studied for the same reaction in protic and non-polar solvents under optimized conditions using CCl₃COOH as catalyst (Table 2).

Table 2 Optimization of solvent at room temperature

Entry	Solvents	Time (min)	Conv. 6a^a^,^b %
a Isolated yields.b Using 1 : 2 : 1 ratio of 2-naphthol, benzaldehyde and aniline with 25 mol% of trichloroacetic acid catalyst.
1	CHCl3/CH2Cl2	30/30	87/85
2	MeOH/EtOH/H2O	30/30/60	90/95/50
3	H2O + EtOH (1 : 1)	40	80

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The homogeneous phases of all reactants in chloroform, dichloromethane and alcohol generated a suitable medium to produce excellent yields of oxazine derivatives within half an hour (Table 2, entries 1–2). Alcohol may be the appropriate solvent for this reaction to increase the stability of reaction intermediates via H-bonding (Table 2, entry 2). The heterogeneous phases of reactant in water had reduced the yield of product to 60% in 1 h reaction (entry 2). The use of 50% aqueous ethanol improved the yield of product to 80% during 40 minutes (entry 3).

After optimization we had extended this study to get structurally diverse novel anti-1,2,3-trisubstituted naphth-[1,3]oxazine 6 as racemic mixture in achiral environment (Scheme 1) by changing both aldehyde and amine compounds.

In a typical procedure, the mixture of 2-naphthol (1 mmol), aldehyde (2 mmol) and primary amine (1 mmol) was stirred at room temperature in ethanol (or treated under solvent-free medium at 100 °C) using 25 mol% of trichloroacetic acid as catalyst for the specified time. After completion of the reaction as monitored by thin layer chromatography the product was isolated as pure solid from the reaction mixture by following a steps of work up procedure.¹⁰ All these results are included in Table 3.

Table 3 Substituent effects on the synthesis of anti-1,2,3-trisubstituted-naphth-[1,3]oxazine derivatives

Entry	R^1	R	Time (min)	Product(s) yield^a^,^d (%)
				18	6	23	24
a Isolated yields.b Reaction in ethanol at room temperature.c Reaction in solvent-free medium at 100 °C.d 23 and 24 are known compounds.^11e Using 1-naphthol as starting compound.
1	8	13/14	30^b/30^b	—	85(6a)/82(6b)	—
2	8	13/14	20^c/20^c	—	92(6a)/96(6b)	—
3	8	16/15	30^b/40^b	—	90(6c)/85(6d)	—
4	8	16/15	20^c/25^c	—	94(6c)/92(6d)	—
5	8	17	2 h^b/1 h^c	85/40	—	–/25	–/30
6	9	16	30^b/30^c	—	82/92(6f)	—	—
7	10	13/16	40^b/30^b	87/–	–/85(6h)	—	—
8	10	13/16	20^d/30^d	18/–	–/92(6h)	60/–	15/–
9	11	13/16	12 h^b/45^b	88/–	–/80(6j)	—
10	11	13/16	40^c/30^c	20/–	–/87(6j)	—	65/–
11	12	13/16	2 h^b/1 h^b	20/25	—	—
12	12	13/16	1 h^c/1 h^c	15/5	—	—	60/65
13	8^e	13/16	1 h^b/1 h^b	86/88	—	—	—

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The one pot synthesis of anti-1,2,3-trisubstituted naphth-[1,3]oxazine 6 is possible only in situ formation of the reaction intermediates 18, 19, 20, 21 and 22 during the course of reactions (Scheme 2). Another competitive reaction also observed in these multicomponent reactions which leads to the formation of dibenzoxanthene derivative 24 and its precursor 23. The success of this method depends on the reversible nature of imine bond formation followed by driving the protonation of imine in one direction under thermodynamic equilibrium to form 1-alkylaminomethyl 2-naphthol intermediate 21.¹² Then nucleophilic attack of this intermediate to the second aldehyde molecule yield the stable naphthoxazine derivatives 6. The protonation of imine equilibrium can be driven in the favor of desired product by adjusting acidity of catalyst, solvent and temperature, steric and electronic factors of substrates. We observed higher yields (80–94%) of naphthoxazines from the reaction of aromatic aldehydes and aliphatic primary amines in both conditions (Table 3, entries 3, 4, 6–10) with the formation of electron rich N-alkyl substituted imine. The same type of imines could be obtained from 4-isopropyl aniline and benzaldehyde (entries 1 and 2). Electron deficient imine had no tendency for protonation to give the required product in solution (entry 5 and 7). Furthermore, in solvent-free medium the acid catalysed activation of carbonyl group observed the preferred path to get dibenzoxanthene products instead of electron deficient imine (entries 5, 8 and 10). The rapid reversible equilibrium of aldimine obtained from n-butanal prevents the formation of desired product in solution (entry 11). Significantly the high temperature reaction directed to the synthesis of dibenzoxanthene product 24 in dry medium (entry 12). Formations of imines were the only products from the reactions of 1-naphthol with aromatic aldehydes and electron rich amines in solution (entry 13). All these new products were characterized by ¹H NMR, ¹³C NMR, FT-IR and CHN analytical techniques.

Scheme 2 Plausible mechanism.

The exact orientation of naphth-[1,3]oxazine diastereomer was determined from the COSY and NOESY interaction of H-2 and H-4 protons of oxazine ring of the compounds 6a and 6j. They showed two singlets within the chemical shift values of 5.48–6.08 ppm and 5.79–6.24 ppm without any cross peak in their COSY and NOESY spectra which is possible only by anti-orientation of H-2 and H-4 protons in pseudo-axial equatorial conformation of oxazine ring (Fig. 2). The HETCOR spectra of these two compounds assigned the positions of two singlet's by their cross peak with C-2 and C-4 carbons of the oxazine moiety. The three DEPT spectra 135°, 90°, and 45° of 6a are identical. For 6j, the DEPT-135 spectrum reveals three negative signals for –CH₂– groups, four positive signals for two –CH– and three –CH₃ groups in the aliphatic region and other positive signals for –CH– atoms of aromatic region while no peaks for quaternary carbons.

Fig. 2 Pseudo-axial -equatorial conformation of oxazine ring.

Cambridge Structural Database (CSD)¹³ shows no structural report for this series of compounds, except 6c and 6d.^9b,c Crystals of 6c have regrown and the structure was evaluated with better data parameter ratio in comparison with reported structure. The C–H⋯O and π⋯π interactions are predominant in generating 3D structure of 6c (Fig. 3a). Literature reveals only the emphasis on conformational studies of oxazine family specially naphthoxazine by NMR and semi empirical minimization theory.^7d,9a Difficulties in growing suitable crystals for this class of compounds ensue single report in CSD. We were able to crystallize out colourless block crystal of compound 6b from 1 : 1 ethanol–chloroform solvent mixture. Single crystal X-ray data were collected.

Fig. 3 (a) Crystal structure of compound 6c, (b) molecular packing shows C–H⋯O and π⋯π interactions in compound 6b, (c) overlay of two symmetry independent molecules of structure 6b shows a narrow angle deviation in the isopropyl group.

Conclusion

In conclusion, we have reported two sets of efficient multicomponent conditions for the selective synthesis of anti-2,3-dihydro-1,2,3-trisubstituted-1H-naphth[1,2-e][1,3]-oxazine for the first time in higher yields utilizing a mixture of 2-naphthol, aryl aldehyde and electron rich primary amines in solution as well as in solvent-free medium using trichloroacetic acid catalyst. The present approach has the ability to synthesize a variety of structurally diverse anti-trisubstituted-napth-[1,3]oxazines derivatives within short time. In addition, it has opened up the possibility of asymmetric synthesis of 1,2,3-trisubstituted-naphth-[1,3]oxazine products in the near future.

Experimental section

General methods

All the chemicals and solvents were obtained from Merck, Alfa-aser, Aldrich and used as received without any further purification. TLC was monitored on silica gel glass plate. Melting points were determined in a digital melting point apparatus. The NMR spectroscopic data of oxazine derivatives were recorded in CDCl₃ with a JEOL 400 MHz spectrometer using TMS as internal standard. Coupling constants are (J) expressed in Hertz (Hz), and spin multiplicities are given as s (singlet), d (doublet), t (triplet), m (multiplet), dd (double doublet). IR spectra of all compounds were recorded on a Nicolet Impact-410 spectrometer. Elemental analyses were done with Perkin Elmer 20 analyzer. All new products were identified by FT-IR, ¹H NMR, ¹³C NMR spectroscopic data and CHN analyses. We had taken COSY, NOESY, HETCOR and DEPT spectra of two compounds (6a and 6j) to identify exact orientation of naphthoxazine diastereomers. All these spectra are included as soft copy in the ESI.†

General procedure for the syntheses of 2,3-dihydro-1,2,3-trisubstituted-1H-naphth[1,2-e][1,3]oxazine derivatives. A mixture of 2-naphthol (1 mmol), primary amine (1 mmol), and aldehydes (2 mmol) was stirred at room temperature in ethanol (2 mL) or heated in an oil bath for the specified time in absence of any solvent at 100 °C using 0.25 mmol of trichloroacetic acid as catalyst. After completion of the reaction as monitored by TLC, the reaction mixture was diluted with 5 mL of dichloromethane and washed with an aqueous solution of sodium hydroxide for removal of unreacted 2-naphthol and acid catalyst. The product mixture was extracted with dichloromethane (3 × 3 mL) and distilled under reduced pressure to get the crude mixture in rotary evaporator. The pure product was precipitated from the saturated solution of crude mixture in ethanol at room temperature.

Spectral analysis of the prepared compounds.
1. 2,3-Dihydro-1,2,3-triphenyl-1H-naphth[1,2-e][1,3]oxazine (Tables 3 and 6a). White amorphous solid, m.p.: 206–207 °C; FT-IR (KBr) cm⁻¹: 3030, 2918, 1596, 1494, 1449, 1396, 1335, 1222, 944, 703; ¹H NMR (CDCl₃, 400 MHz): δ 6.08 (d, J = 4.1 Hz, 1H), 6.25 (d, J = 5.1 Hz, 1H), 6.85–6.88 (m, 1H), 7.01–7.06 (m, 2H), 7.18–7.37 (m, 12H), 7.48 (d, J = 6.9 Hz, 2H), 7.55 (d, J = 6.9 Hz, 2H), 7.78–7.83 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ 65.3, 84.3, 113, 119.1, 123.1, 123.4, 123.6, 125.4, 126.6, 127.6, 127.9, 128.4, 128.5, 129.2, 129.3, 129.5, 137.3, 142.8, 147.1, 153; CHN analysis (%): C₃₀H₂₃NO, cal. C 87.17, H 5.57, N 3.39%; found C 87.23, H 5.54, N 3.43%.

The COSY, NOESY, HETCOR and DEPT spectra are included in the ESI.†

2. 2,3-Dihydro-2-(4-isopropylphenyl)-1,3-diphenyl-1H-naphth[1,2-e][1,3]oxazine (Tables 3 and 6b). White solid; m.p.: 171–173 °C; FT-IR (KBr) cm⁻¹: 3026, 2953, 2379, 2150, 1606, 1507, 1451, 1397, 1336, 1222, 954, 813, 704; ¹H NMR (CDCl₃, 400 MHz): δ 1.08 (s, 6H), 2.68 (m, 1H), 6.04 (d, J = 5.1 Hz, 1H), 6.21 (d, J = 5.1 Hz, 1H), 6.87 (m, 2H), 7.08 (m, 2H), 7.20–7.38 (m, 10H), 7.45–7.48 (m, 2H), 7.54 (m, 2H), 7.78–7.82 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ 23.8, 23.9, 30.9, 33.2, 65.2, 84.5, 113.6, 119.2, 123.2, 123.4, 125.2, 126.4, 126.6, 126.7, 127.5, 127.9, 128.4, 128.5, 129.3, 129.4, 137.5, 143, 144, 144.8, 153.1; CHN analysis (%): C₃₃H₂₉NO, cal. C 87.03, H 6.37, N 3.08%; found C 87.12, H 6.41, N 3.11%.
3. Butyl-2,3-dihydro-1,3-diphenyl-1H-naphth[1,2-e][1,3]oxazine (Tables 3 and 6c). White crystalline solid; m.p.: 133–135 °C; FT-IR (KBr) cm⁻¹: 3062, 2946, 2848, 1601, 1507, 1452, 1392, 1333, 1233, 1125, 945, 813, 700; ¹H NMR (CDCl₃, 400 MHz): δ 0.77 (t, J = 7.3 Hz, 3H), 1.12–1.19 (m, 1H), 1.29–1.36 (m, 1H), 1.53–1.64 (m, 2H), 2.35–2.40 (m, 1H), 2.58–2.64 (m, 1H), 5.54 (s, 1H), 5.82 (s, 1H), 7.22–7.37 (m, 11H), 7.44 (d, J = 7.4 Hz, 1H), 7.55 (d, J = 6.8 Hz, 2H), 7.78–7.82 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ 13.9, 20.2, 31.1, 44.8, 58.9, 85.9, 112.5, 119, 123.1, 123.3, 126.5, 127.1, 127.7, 127.9, 128.2, 128.6, 129.1, 129, 129.5, 138.2, 143.2, 152.9; CHN analysis (%): C₂₈H₂₇NO, cal. C 85.5, H 6.87, N 3.56%; found C 85.54, H 6.91, N 3.58%.
4. Benzyl-2,3-dihydro-1,3-diphenyl-1H-naphth[1,2-e][1,3]oxazine (Tables 3 and 6d). White crystalline solid; m.p.: 191–193 °C; FT-IR (KBr) cm⁻¹: 3023, 2881, 2837, 1595, 1496, 1449, 1391, 1331, 1229, 935, 813, 744, 693; ¹H NMR (CDCl₃, 400 MHz): δ 3.34 (d, J = 13.7, 1 H), 3.88 (d, J = 14.2 Hz, 1H), 5.39 (s, 1H), 5.99 (s, 1H), 7.22–7.24 (m, 7H), 7.30–7.33 (m, 8H), 7.40 (t, J = 7.8 Hz, 2H), 7.68 (d, J = 7.3 Hz, 2H), 7.81–7.85 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ 49.6, 57.8, 85.5, 112.1, 118.8, 123, 123.4, 126.4, 126.6, 127.2, 127.9, 128, 128.2, 128.3, 128.6, 129.2, 129.4, 133.5, 138.1, 139.5, 143.1, 152.6; CHN analysis (%): C₃₁H₂₅NO, cal. C 87.12, H 5.85, N 3.28%; found C 87.17, H 5.88, N 3.30%.
5. 2-Butyl-1,3-bis(4-chlorophenyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazine (Tables 3 and 6f). Yellow solid; m.p.: 163–165 °C; FT-IR (KBr) cm⁻¹: 3227, 2954, 2859, 2377, 1617, 1483, 1399, 1331, 1235, 1088, 948, 815, 745; ¹H NMR (CDCl₃, 400 MHz): δ 0.78 (t, J = 7.2 Hz, 3H), 1.12 (m, 1H), 1.32 (m, 1H), 1.54–1.58 (m, 2H), 2.35 (m, 1H), 2.53 (m, 1H), 5.46 (s, 1H), 5.69 (s, 1H), 7.25–7.27 (m, 5H), 7.32–7.38 (m, 5H), 7.46 (d, J = 8.7 Hz, 2H), 7.79–7.83 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ 13.9, 20.2, 31.1, 44.9, 58.3, 85.4, 111.9, 118.9, 122.8, 123.5, 126.8, 127.9, 128.2, 128.4, 128.7, 129.4, 130.8, 136.5, 141.7, 152.6; CHN analysis (%): C₂₈H₂₅NO, cal. C 72.73, H 5.41, N 3.03%; found C 72.75, H 5.46, N 3.07%.
6. 2-Butyl-2,3-dihydro-1,3-bis(4-nitrophenyl)-1H-naphth[1,2-e][1,3]oxazine (Tables 3 and 6h). Yellow solid; m.p.: 168–171 °C; FT-IR (KBr) cm⁻¹: 3465, 2931, 2854, 1646, 1594, 1531, 1411, 1344, 1184, 1104, 982, 847, 696; ¹H NMR (CDCl₃, 400 MHz): δ 0.78 (t, J = 7.4 Hz, 3H), 1.14 (m, 1H), 1.31 (m, 1H), 1.58–1.62 (m, 2H), 2.44–2.48 (m, 2H), 5.58 (s, 1H), 5.69 (s, 1H), 7.31 (d, J = 8.7 Hz, 2H), 7.39–7.40 (m, 2H), 7.55 (m, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.88 (d, J = 8.7 Hz, 2H), 8.21 (d, J = 8.3 Hz, 2H), 8.24 (d, J = 8.7 Hz, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ 14, 20.3, 31.2, 45.6, 58.6, 85.5, 111, 118.9, 123.5, 123.8, 124.1, 127.3, 127.6, 129.1, 130.5, 144.8, 147.4, 147.9, 150.1, 152.5; CHN analysis (%): C₂₈H₂₅NO, cal. C 69.57, H 5.17, N 8.70%; found C 69.60, H 5.20, N 8.72%.
7. 2-Butyl-2,3-dihydro-1,3-dip-tolyl-1H-naphth[1,2-e][1,3]oxazine (Tables 3 and 6j). Shiny brown solid; m.p.: 165–166 °C; FT-IR (KBr) cm⁻¹: 3297, 2919, 1618, 1510, 1458, 1394, 1234, 938, 809; ¹H NMR (CDCl₃, 400 MHz): δ 0.77 (t, J = 7.4 Hz, 3H), 1.12–1.18 (m, 1H), 1.30–1.37 (m, 1H), 1.53–1.61 (m, 2H), 2.33 (s, 3H), 2.35 (s, 3H), 2.37–2.38 (m, 1H), 2.63–2.66 (m, 1H), 5.49 (s, 1H), 5.8 (s, 1H), 7.09 (d, J = 7.8 Hz, 2H), 7.14 (d, J = 8.3 Hz, 2H), 7.23–7.34 (m, 5H), 7.41–7.45 (m, 3H), 7.75–7.78 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ 14, 20.3, 21.2, 21.3, 44.9, 58.8, 86.1, 112, 119.1, 123.2, 123.3, 126.5, 128.6, 128.7, 128.9, 128.9, 129.5, 135.4, 136.7, 137.3, 153.1; CHN analysis (%): C₃₀H₃₁NO, cal. C 85.51, H 7.36, N 3.33%; found C 85.58, H 7.42, N 3.31%.

The COSY, NOESY, HETCOR and DEPT spectra are Included in the ESI.†

8. Phenyl-bis-(2-hydroxy-1-naphthyl)methane (Table 3, entry-5, 23)¹¹. White solid; m.p.: 203–205 °C; FT-IR (KBr) cm⁻¹: 3422, 2926, 2378, 1953, 1618, 1505, 1436, 1358, 1257, 1210, 1146, 1031, 957, 813, 749, 699; ¹H NMR (CDCl₃, 400 MHz): δ 7.91 (d, J = 8.2 Hz, 2H), 7.8 (d, J = 8.2 Hz, 2H), 7.7 (d, J = 9.1 Hz, 2H), 7.20–7.39 (m, 9H), 7.01 (d, J = 8.7 Hz, 2H), 6.3 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 152.9, 140.6, 133.6, 130.1, 129.9, 129.7, 129, 128.4, 127.5, 123.6, 122.6, 119.9, 118.6, 42.7; CHN analysis (%): C₂₇H₂₀O₂, cal. C 86.17, H 5.31%; found C 86.21, H 5.35%.
9. 14-Phenyl-14H-dibenzo [a.j]xanthene (Table 3, entry-5, 24)¹¹. Pale yellow; m.p.: 182–183 °C; FT-IR (KBr) cm⁻¹: 3066, 3022, 2884, 1620, 1589, 1513, 1486, 1456, 1401, 1250, 1080, 1023, 965, 824, 746, 699; ¹H NMR (CDCl₃, 400 MHz): δ 8.38 (d, J = 8.7 Hz, 2H), 7.78 (d, J = 8.2 Hz, 2H), 7.77 (d, J = 9.1 Hz, 2H), 7.45–0.56 (m, 5H), 7.38 (t, J = 7.8 Hz, 2H), 7.12 (d, J = 7.3 Hz, 2H), 6.96 (t, J = 7.3 Hz, 2H), 6.46 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 148.8, 145, 128.9, 128.7, 128.5, 123.3, 126.8, 124.3, 122.7, 118, 38.1; CHN analysis (%): C₂₇H₁₈O, cal. C 90.5, H 5.02%; found C 90.57, H 5.08%.
10. 4-Nitrophenyl-bis-(2-hydroxy-1-naphthyl)methane (Table 3, entry-8, 23). Yellow solid; m.p.: 145–147 °C; FT-IR (KBr) cm⁻¹: 3394, 2927, 2858, 2379, 2285, 1603, 1511, 1342, 1257, 1209, 1147, 954, 811, 743; ¹H NMR (CDCl₃, 400 MHz): δ 8.06 (d, J = 6.9 Hz, 2H), 7.92 (d, J = 8.2 Hz, 2H), 7.81 (d, J = 7.3 Hz, 2H), 7.68 (d, J = 8.2 Hz, 2H), 7.24–7.42 (m, 7H), 6.98 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ 152.2, 150.4, 146.5, 135, 130.3, 129.3, 128.6, 127.7, 123.9, 123.7, 122.2, 119.3, 118.1, 42.2; CHN analysis (%): C₂₇H₁₉O₄N, cal. C 76.95, H 4.51, N 3.33%; found C 77.10, H 4.55, N 3.36%.
11. 14-(4-Nitrophenyl)-14H-dibenzo[a.j]xanthene (Table 3, entry-8, 24)¹¹. Light yellow; m.p.: 303–305 °C; FT-IR (KBr) cm⁻: 3418, 2924, 2853, 2372, 2188, 1719, 1591, 1509, 1397, 1335, 1240, 1099, 952, 810, 741; ¹H NMR (CDCl₃, 400 MHz): δ 8.28 (d, J = 8.2 Hz, 2H), 7.99 (d, J = 8.2 Hz, 2H), 7.81–7.85 (m, 4H), 7.65 (d, J = 8.3 Hz, 2H), 7.58 (t, J = 7.8 Hz, 2H), 7.50 (d, J = 9.2 Hz, 2H), 7.40–7.44 (m, 2H), 6.95 (s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 152, 148.9, 146.4, 131.1, 129.7, 129.1, 129, 127.3, 124.7, 123.9, 122.1, 118.1, 116, 37.9; CHN analysis (%): C₂₇H₁₇O₃N, cal. C 80.39, H 4.21,N 3.47%; found C 80.43, H 4.24, N 3.51%.
12. 14-(4-Methylphenyl)-14H-dibenzo [a.j]xanthene (Table 3, entry-10, 24)¹¹. Yellow solid; m.p.: 227–228 °C; FT-IR (KBr) cm⁻¹: 3068, 2917, 1626, 1597, 1515, 1466, 1437, 1404, 1258, 1125, 1087, 967, 840, 815, 785, 745; ¹H NMR (CDCl₃, 400 MHz): δ 7.69–7.78 (m, 3H), 7.36 (d, J = 7.8 Hz, 3H), 7.27 (t, J = 6.9 Hz, 1H), 7.13–7.16 (m, 6H), 6.91 (t, J = 7.3 Hz, 1H), 6.77 (d, J = 7.8 Hz, 2H), 6.14 (s, 1H), 2.3 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ 156, 146.5, 138.4, 130, 129.9, 129.4, 129.1, 128.9, 127.9, 126.8, 122.8, 121.4, 199.9, 116.5, 11.8, 62.7, 21.1; CHN analysis (%): C₂₈H₂₀O, cal. C 90.32, H 5.37%; found C 90.37, H 5.40%.
13. 14-(n-Butylphenyl)-14H-dibenzo [a.j]xanthene (Table 3, entry-12, 24)¹¹. Off white; m.p.: 172–175 °C; FT-IR (KBr) cm⁻¹: 3045, 2920, 1621, 1588, 1558, 1514, 1455, 1384, 1237, 1209, 1138, 1100, 1043, 965, 825, 745; ¹H NMR (CDCl₃, 400 MHz): δ 8.26 (d, J = 8.7 Hz, 2H), 7.87 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 8.7 Hz, 2H), 61 (t, J = 8.2 Hz, 2H), 7.44 (t, J = 7.8 Hz, 2H), 7.33 (d, J = 8.7 Hz, 2H), 5.56 (s, 1H), 1.98–2.02 (m, 2H), 0.97–1.03 (m, 1H), 0.83–0.88 (m, 1H), 0.59 (t, J = 7.4 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ 148.9, 129.99, 127.8, 127.1, 125.5, 123, 121.4, 116.5, 115.7, 37.2, 29.9, 17.1, 13.0; CHN analysis (%): C₂₄H₂₀O, cal. C 88.88, H 6.17%; found C 88.92, H 6.21%.

Acknowledgements

The authors are thankful to Sophisticated Analytical Instrumentation Centre, Tezpur University, for analysis of various samples for this work and also to CSIR, New Delhi, India for granting a research project no. 02(0067)/12/EMR-II to R. B.

Notes and references

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13. ESI.†.

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Footnote

† Electronic supplementary information (ESI) available: This documents contains the ¹H NMR and ¹³C NMR spectra of products 6; COSY, NOESY, HETCOR and DEPT spectra of 6a and 6j; and the crystal structure of 6b and 6c. CCDC 968939 and 968940. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3ra47211f

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