Trends in Green Chemistry Open Access

Keywords

Manganese (IV) oxide; One-pot procedure; 12-aryl-tetrahydrobenzo[α] xanthene-11-one derivatives; Solvent-free conditions; Simple work up

Introduction

Multi-component reactions (MCRs) [1-4] play an important role in combinatorial chemistry with high atom economy due to their ability to synthesize biologically active heterocyclic compounds. Xanthene derivatives possess a variety of pharmaceutical and biological activities. The compounds with xanthene derivatives ring systems are reported as antiplasmodial [5], antiviral [6], anti-inflammatory [7]. Besides, these heterocyclic molecules have been widely used as pH sensitive fluorescent materials for visualization of biomolecules [8,9], laser technology [10,11] and luminescent dyes [12].

In recent decades, a number of methodologies for preparation of these compounds have been reported that is including various catalysts [13-22]. Some of these methodologies have limitations such as difficult work-up, toxic and expensive catalysts, low yields, use of strongly acidic conditions and longtime reactions. Therefore, the development of facile method for the synthesis of xanthene derivatives is of great importance. In continuation of our research work on the synthesis of 12-aryltetrahydrobenzo[ α]xanthene-11-ones, herein we wish to report commercially available Manganese (IV) oxide (MnO₂) as inexpensive, readily and mild catalyst, for the one-pot synthesis of 12-aryl-tetrahydrobenzo[α]xanthene-11-one derivatives by means of three-component domino reaction of β-naphthol, aryl aldehyde derivatives and dimedone. Efficient, readily and lowcost catalyst, good to high yields and short reaction times that makes our protocol alternative in comparison to some of the earlier reported methods. Furthermore, one of the source of environmental pollutions is the usage of organic solvents under reflux conditions and the need for column chromatography to purity the products. In this present work, the products were obtained through simple filtering with no need column chromatographic separation.

Experimental Methods

Melting points of all compounds were determined using an Electro thermal 9100 apparatus. Also, nuclear magnetic resonance, 1H NMR spectra were recorded on a Bruker DRX- 400 Avance instruments with CdCl3 as solvents (Figure 1). In this article, all reagents and solvents were purchased from Merck, Fluka and Acros chemical companies were used without further purification.

Figure 1: The ¹H NMR spectra of one of the products clearly indicated the formation of 9,9-dimethyl-12-(4-methoxyphenyl)-8,9,10,12- tetrahydrobenzo[a]xanthen-11-one (4m) in the presence of Manganese (IV) oxide.

General procedure for preparation of 12-aryltetrahydrobenzo[α]xanthene-11-one derivatives (4a-o)

A mixture of β-naphthol (1, 1.0 mmol), aromatic aldehyde derivatives (2, 1.0 mmol), dimedone (3, 1.0 mmol) and MnO₂ (20 mol%) was heated at 90°C for appropriate time. After completion of the reaction (by thin layer chromatography TLC) the mixture was cooled to r.t. and ethanol was added and the precipitated was separated with filtration and solid was recrystallized from ethanol to afford the pure products (4a-o).The products have been characterized by melting points and ¹H NMR spectroscopy. Spectra data of selected and known product are represented below:

9,9-dimethyl-12-(4-methoxyphenyl)-8,9,10,12-tetrahydrobenzo[a] xanthen-11-one(4m):

White solid; Yield: 82%; Melting point (Mp): 201-203°C.

1HNMR (400 MHz, CdCl₃): 0.99 (3H, s, CH₃), 1.12 (3H, s, CH₃), 2.16- 2.35 (2H, m, CH₂), 2.58 (2H, s, CH₂), 3.71 (3H, s,OCH₃), 5.68 (1H, s, CHAr), 6.72 (2H, d, J=8.4 Hz, ArH), 7.21-7.47 (5H, m, ArH), 7.85 (2H, t, J=9.2 Hz, ArH), 8.01 (1H, d, J=8.4 Hz, ArH).

Results and Discussion

Recognizing the solvent free-based processes as eco-friendly methodology for the synthesis of organic compounds, we conceived the preparation of 12-aryl-tetrahydrobenzo[α] xanthene-11-one derivatives from the reaction between β-naphthol (1), aryl aldehyde derivatives (2) and dimedone (3) catalyzed by Manganese (IV) oxide (MnO₂) (Scheme 1). In order to determine the optimal reaction conditions, we screened different amounts of MnO₂ (5-25 mol%) at range of rt-100°C in the absence of solvent (Table 1) using β-naphthol, benzaldehyde and dimedone as a model reaction. When the amount of MnO₂ was increased from 5 to 20 mol%, the yield of product was improved from 32 to 86% (Table 1, entries 2-5). However, when the amount of MnO₂ was increased to 25 mol%, a remarkable increase in the yield of the product was not observed (Table 1, entry 12). Consequently, the amount of 20 mol% for MnO₂ was selected as the optimized amount of the catalyst for this procedure. The reasonable results were observed when the reaction was performed at 90°C (Table 1, entry 5). The Increment of the temperature up to 100°C (Table 1, entry 11) didn’t significantly improve the reaction results. The efficiency of this protocol was examined by the reaction of a variety of aryl aldehydes with electron-donating and electronwithdrawing groups with β-naphthol and dimedone and the results are summarized in Table 2 (4a-o).

Entry	MnO2 (mol%)	Temperature (°C)	Time (min)	Isolated Yields (%)
1	Catalyst free	90	360	trace
2	5	90	65	32
3	10	90	35	55
4	15	90	20	74
5	20	90	15	86
6	20	rt	360	trace
7	20	40	90	26
8	20	60	65	43
9	20	70	40	65
10	20	80	20	71
11	20	100	15	87
12	25	90	15	88
aReaction conditions: β-naphthol (1.0 mmol); benzaldehyde (1.0 mmol); dimedone (1.0 mmol) and MnO2 was heated under various temperatures for the appropriate time.

Table 1: Optimization of the reaction condition for the synthesis of 4aa.

Entry	R	Product	Time (min)	Isolated Yields (%)	Mp (°C)	Literature Mp (°C)
1	C6H5	4a	15	86	147-149	148-150 [17]
2	4-F- C6H4	4b	15	89	182-184	184-185 [13]
3	4-O2N-C6H4	4c	15	87	176-178	175-178 [19]
4	3-O2N-C6H4	4d	10	85	168-170	167-169 [13]
5	4-Br- C6H4	4e	25	77	183-186	184-186 [17]
6	3-Br- C6H4	4f	25	81	164-166	161-164 [19]
7	4-Me- C6H4	4g	15	88	170-172	171-173 [17]
8	3-Me- C6H4	4h	15	91	180-181	178-180 [16]
9	4- Cl-C6H4	4i	25	79	178-180	176-178 [17]
10	3- Cl-C6H4	4j	25	81	179-181	178-180 [22]
11	2- Cl-C6H4	4k	20	83	177-179	179-180 [20]
12	2, 4- Cl2-C6H3	4l	30	76	184-186	183-184 [22]
13	4-OMe- C6H4	4m	20	82	201-203	202-204 [17]
14	2-OMe- C6H4	4n	15	89	167-169	165-167 [22]
15	4-OH- C6H4	4o	25	78	220-222	222-223 [17]

Table 2: MnO₂ catalyzed synthesis of 12-aryl-tetrahydrobenzo[α]xanthene-11-ones.

Comparison of catalytic ability some of catalysts reported in the literature for synthesis of 12-aryl-tetrahydrobenzo[α]xanthene- 11-one derivatives are shown in Table 3. This study reveals that MnO₂ has shown its extraordinary potential to be an alternative inexpensive, readily and efficient catalyst for the one-pot synthesis of these biologically active heterocyclic compounds, in addition good to high yields and short reaction times under solvent-free conditions are the notable advantages this present methodology.

Table 3: Comparison of catalytic ability some of catalysts reported in the literature for synthesis of 12- aryl-tetrahydrobenzo[α]xanthene-11-onesa.

Conclusion

Extremely facile and efficient procedure have been developed for the synthesis of 12-aryl-tetrahydrobenzo[α]xanthene- 11-one derivatives. One-pot three-component reaction of β-naphthol, aromatic aldehyde derivatives and dimedone in the presence of Manganese (IV) oxide (MnO₂) as efficient, readily and inexpensive catalyst under solvent-free conditions provides these biologically active heterocyclic compounds. Operational simplicity, inexpensive catalyst, enhanced rates, short reaction times and good to high isolated yields of the pure products are notable advantages of this eco-friendly protocol.

Acknowledgments

We gratefully acknowledge financial support from the Young Researchers and Elite Club, Shiraz Branch, Islamic Azad University of Shiraz.

References

1. Mohamadpour F, Maghsoodlou MT, Heydari R, Lashkari M (2016)Saccharin: a green, economical and efficient catalyst for the one‑pot, multi‑component synthesis of 3,4‑dihydropyrimidin‑2‑(1H)‑one derivatives and 1H‑pyrazolo[1,2‑b] phthalazine‑5,10‑dione derivatives and substituted dihydro‑2‑oxypyrrole. J Iran Chem Soc   13: 1549-1560.
2. Mohamadpour F, Maghsoodlou MT, Heydari R, Lashkari M (2016)Copper(II) acetate monohydrate: an efficient and eco-friendly catalyst for the one-pot multi-component synthesis of biologically active spiropyrans and 1-Hpyrazolo[1,2-b]phthalazine-5,10-dione derivatives under solvent-free conditions. Res Chem Intermed 42: 7841-7853.
3. Mohamadpour F, Maghsoodlou MT, Heydari R, Lashkari M (2016)Tartaric Acid: A Naturally Green and Efficient Di-Functional Brønsted Acid Catalyst for the One-Pot Four-Component Synthesis of Polysubstituted Dihydropyrrol-2-Ones at Ambient Temperature. Iran Sci Technol Trans Sci.
4. Mohamadpour F, Maghsoodlou MT, Heydari R, Lashkari M (2017)One-pot Synthesis of Polysubstituted Dihydro-2- oxypyrroles Catalyzed by Vanadium (V) oxide. J Appl Chem Res 11: 115-123.
5. Zelefack F, Guilet D, Fabre N, Bayet C, Chevalley S, et al. (2009)Cytotoxic and antiplasmodial xanthones from Pentadesma butyracea. J Nat Prod 72: 954-957.
6. Lambert RW, Martin JA, Merrett JH, Parkes KEB, Thomas GJ (1997)PCT Int Appl WO Chem Abstr 126: 212377y.
7. Poupelin JP, Saint-Rut G, Foussard-Blanpin O, Narcisse G, Uchida-Ernouf G (1978) Synthesis and anti-inflammatory properties of bis(2-hydroxy-1-naphthyl)methane derivatives. I. Monosubstituted derivatives. Eur J Med Chem 13: 67-71.
8. Callan JF, De Silva P, Magri DC (2005) Luminescent sensors andswitches in the early 21st century Tetrahedron 61: 8551-8588.
9. Liu J, Diwu Z, Leung WY (2001) Synthesis and photophysicalproperties of new fluorinated benzo[c]xanthene dyes as intracellular pH indicators. Bioorg Med Chem Lett 11: 2903-2905.
10. Banerjee A, Mukherjee AK (1981) Chemical aspects of santalin as ahistological stain, Stain Technol 56: 83-85.
11. Ahmad M, King TA, Ko DK, Cha BH, Lee J (2002) Performance andphotostability of xanthene and pyrromethene laser dyes in sol-gel phases. J Phys D: Appl Phys 35: 1473-1476.
12. Fleming GR, Knight AWE, Morris JM, Morrison RJS, Robinson GW(1977) Picosecond fluorescence studies of xanthenes dyes. J Am Chem Soc 99: 4306-4311.
13. Nemati F, Sabaqian S (2014) Nano-Fe3O4 encapsulated-silica particlesbearing sulfonic acid groups as an efficient, eco-friendly and magnetically recoverable catalyst for synthesis of various xanthene derivatives under solvent-free conditions, J Saudi Chem Soc.
14. Das B, Laxminarayana K, Krishnaiah M, Srinivas Y (2007) An efficientand convenient protocol for the synthesis of novel 12-aryl- or 12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives. Synlett 3107-3112.
15. Huang H, Yao Y, Lin Q, Zhao J, Hu C, et al. (2016) One-pot synthesisof xanthene derivatives catalyzed by Fe(III) tetranitrophthalocyanine immobilized on activated carbon, Russ J Gen Chem 86: 934-938.
16. Heravi MM, Alinegjhad H, Bakhtiari K, Oskooie HA (2010) Sulfamicacid catalyzed solvent-free synthesis of 10-aryl-7,7-dimethyl- 6,7,8,10-tetrahydro-9H-[1,3]-dioxolo [4,5-b]xanthen-9-ones and 12-aryl-9,9-dimethyl-8,9,10,12-tetrahydro-11H-benzo[a]xanthen- 11-one. Mol Divers 14: 621-626.
17. Shirini F, Yahyazadeh A, Mohammadi K (2014) One-pot synthesis ofvarious xanthene derivatives using ionic liquid 1,3-disulfonic acid imidazolium hydrogen sulfate as an efficient and reusable catalyst under solvent-free conditions. Chin Chem Lett 25: 341-347.
18. Sudha S, Pasha MA (2012) Ultrasound assisted synthesis oftetrahydrobenzo[c]xanthene-11-ones using CAN as catalyst. Ultra Sonochem 19: 994-998.
19. Khazaei A, Zolfigol MA, Moosavi-Zare AR, Zare A, Khojasteh M, et al.(2012) Organocatalyst trityl chloride efficiently promoted the solventfree synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11- ones by in situ formation of carbocationic system in neutral media. Catal Commun 20: 54-57.
20. Nemati F, Arghan M, Amoozadeh A (2012) Efficient, solvent-free methodfor the one-pot condensation of b-naphthol, aromatic aldehydes, and cyclic 1,3-dicarbonyl compounds catalyzed by silica sulfuric acid. Synth Commun 42: 33-39.
21. Li J, Tang W, Lu L, Su W (2008) Strontium triflate catalyzed one-potcondensation of β-naphthol, aldehydes and cyclic 1,3-dicarbonyl compounds. Tetrahedron Lett 49: 7117-7120.
22. Li JT, Li YW, Song YL (2012) Efficient synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a] xanthen-11-one Derivatives catalyzed by p-dodecylbenzenesulfonic acid in aqueous media under ultrasound irradiation. Synth Commun 42: 2161-2170.