Facile Synthesis of Electroluminescence Acridinedions by Microwave and Ultrasound

P. Murugan, Kuo Chu Hwang, V. T. Ramakrishnan and S. Balasubramanian

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Posted: September 2005

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Abstract

Keywords

Introduction

Experimental

Results and Discussion

Conclusion

Acknowledgements

References

Contact Details

Abstract

Various highly fluorescent acridinediones were synthesized by microwave and ultrasound irradiations, as well as by conventional thermal methods.  It was found that most of the acridinedione derivatives could be obtained in very high yields (80~90%) in the microwave- assisted, solvent-free, one-pot synthesis process within minutes (~2 min).  These highly fluorescent acridinediones are potential new materials for electroluminescence (EL) devices.

Keywords

Acridinediones, Tetraketones, Xanthanes, Microwaves, Ultrasonication

Introduction

The cyclic ring system of acridinedione analogues is generally considered to be one of the most broadly involved rings in heterocyclic compounds.  Many acridinedione derivatives have been investigated for their potential as laser dyes [1-6], photo chemical/ physical properties [7-9], electrochemical properties [10], and interactions with DNA [11].  Their analogues show potent anti-malarial activity [12] and possess similar properties as those of 1,4-dihydropyridines, which have similarities in structures to Nicotinamide Adenine Dinucleotide (NADH) and Nicotinamide Adenine Dinucleotide Phosphate (NADPH).  Due to their strong fluorescence properties, acridinedione derivatives are quite good laser dyes, and are of great potential to be electroluminescence (EL) materials [1-6].  Generally, acridinediones were prepared by reaction of tetraketones (1) with aqueous ammonia or respective amines in the presence of catalytic amount of P₂O₅ in ethanol at room temperature, which usually results in moderate yields [1-6].  The yields can be improved if the reactions are carried out in boiling acetic acid.   In this paper, we wish to report a very convenient, short time, high yield, and low cost, one-pot synthesis of these acridinedione derivatives by irradiation of microwave ultrasonication.  

Microwave is a very convenient energy source, and is becoming more and more commonly used in synthetic organic chemistry [13-15].  In literature, the mechanism of microwave-assisted organic reactions is rarely discussed.  In general, the higher the polarity of a moiety is, the stronger the microwave absorption it will be [16].  The great advantages of microwave-assisted synthesis of organic compounds are the much shorter reaction time and higher yields than the conventional thermal methods.  Many reactions can be completed within minutes (or, sometimes, even in seconds) in a microwave oven as compared to hours or days by conventional thermal methods.  A solvent-free condition is one of the special advantages of microwave-assisted reactions.  A number of heterocyclic compounds have been synthesized under solvent-free conditions without supporting materials, such as, alumina, silica, clay, or “doped” surfaces (e.g., Fe(NO₃₎₃-clay,NaIPO₄-clay [17-19]).  In the case of solvent-free reactions, the microwave is absorbed directly by the reagents, which often leads to very high reaction efficiency.  Furthermore, these microwave-assisted, solvent-free reactions can be carried out in open vessels without requirement of any specialized vessels.  Contrary to microwave, ultrasonication is also applied as the energy source for organic reactions [20-25]. 

Concerning the ultrasound irradiation, most of the observed effects of ultrasound on chemical reactions can be attributed to cavitation, the formation and subsequent collapse of small micro bubbles inside the liquid phase [26].  The pressure and temperature inside the micro bubbles are estimated to be about ~1000 atmosphere and 4000~5000 K [26].  The high pressure is especially favorable to condensation reactions, since the product has a smaller volume than those of the reactants.  The formation of micro-cavitation is non-selective.  Thus, the effect of ultrasound on the synthesis of acridinediones is not as efficient as microwave, but still better than the thermal method (based on reaction time). 

Experimental

IR spectra were recorded on Bomem-FTIR spectrophotometer, with all compounds compressed in KBr pellets.  NMR spectra were obtained on Varian 300 MHz ¹H NMR (or 75 MHz for 13C) spectrometer.  All microwave reactions were carried out with a power strength of 900 W.  Reactions under ultrasound irradiation were performed in an ultrasound cleaner bath (Misonix, XL2020, 450 W) at 70 – 75°C.  The absorption spectra were recorded using a Hitachi,U-3300 spectrophotometer.  The fluorescence spectra were recorded using a Jasco Fp-777 spectrophotometer.  HRMS (High Resolution Mass Spectra) data were recorded using a Thermo Finnigan (Model: MAT 95 XL).

Thermal method for synthesis of 2a-i and 3a-r.  The tetraketones (0.5 mmol) and ammonium acetate (excess) or respective amines (0.5 mmol) were refluxed (time indicated in Table 1 and 2) in acetic acid.  The reaction mixture was cooled and poured into crushed ice.  The yellow solid obtained was filtered, dried and re-crystallized from MeOH: CHCl₃ (1:1). 

Table 1. Comparison of product yields of acridinediones under microwave irradiation, ultrasound and conventional thermal methods.

a. All reactions were carried out under refluxing in acetic acid.

b. Microwave power is 900 W.

Table 2.  Comparison of product yields of acridinediones derivatives by using microwave irradiation, ultrasound and conventional thermal methods.

a. All reactions were carried out under refluxing in acetic acid.

b. Microwave power is 900 W.

Microwave method for synthesis of 2a-i.  The tetraketones (0.1mmol) were charged in an open pyrex vessel.  The vessel was irradiated in a domestic microwave oven for the time and power indicated in Table 1.   After irradiation, the reaction mixture was cooled and crushed ice added, the separated yellow solid was filtered, dried and re-crystallized from MeOH: CHCl₃ (1:1).  Concerning compounds 3a-r, the corresponding tetraketones (0.1 mmol) and amines (0.1 mmol) and acetic acid (5 ml) were charged in a pyrex vessel.  The pyrex vessel was irradiated in a domestic microwave oven for the time and power indicated in Table 2.  After irradiation, the reaction mixture was cooled and the workup of the reaction mixture was same as above described in the thermal method. 

General procedure for ultrasound synthesis of 2a-i and 3a-r.  The solution of tetraketones (0.1mmol), ammonium acetate (excess) or amines (0.1mmol) in acetic acid (5ml) was irradiated with ultrasound for the times and the temperature indicated in Table 1 and 2.  After irradiation, the reaction mixture was cooled and the workup of the reaction mixture was same as described in above thermal reactions.

The physical and spectroscopic data for the acridinediones are listed below:

2h. (4-Chlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8-(2H, 5H) acridinedione: mp>300°C; IR (KBr) 3280, 1640, 1532 cm-1; uv (MeOH) 378 nm; fluores (MeOH) 445 nm; ¹H NMR (300 MHz, CDCl₃): δ0.96, 1.07 (2s, 12H, gem dimethyl), 2.19 (s, 4H, C₂-CH₂), 2.12-2.36 (ABq, J= 16.2Hz, C₄-CH₂), 5.05 (s,1H, =C-CH-C=), 6.90 (bs, 1H, NH), 7.14-7.29 (ABq, 4H, Ar-H); HRMS found; m/z 383.1607, calcd for C₂₃H₂₆NClO₂: 383.1645.

2i. 9-(n-Nonyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H) acridinedione: mp 135-137°C; IR (KBr) 3310, 1645, 1540 cm^-1; uv (MeOH) 375 nm; fluores (MeOH) 460 nm; ¹H NMR (300 MHz, CDCl₃): Δ0.87 (t, 3H, CH_3-(CH₂)_8-), 1.12, 1.13 (2s, 12H gem dimethyl), 1.20-1.81 (m, 16H,-(CH₂)_8-), 2.27 (s, 4H, C₂-CH₂), 2.33, 2.42 (ABq, 4H, C_4-CH₂), 4.09 (t, 1H, =C-CH-C=), 7.60 (bs, 1H, NH); HRMS found: m/z 397.2976, calcd for C₂₆H₃₉NO₂: 397.2971.

3m. 10-(3-Iodophenyl)-3,4,6,7,9,10-hexahydro-1,8(2H,5H) acridinedione: mp 256-258°C; IR (KBr) 1631, 1548 cm^-1; uv (MeOH) 380 nm; fluores (MeOH) 463 nm; ¹H NMR (300 MHz, CDCl₃) δ1.87 (m, 8H, =C-CH₂-CH_2-), 2.34 (m, 4H, -C-CO-CH₂-), 3.21 (s, 2H, =C-CH₂-C=), 7.23-7.82 (m, 4H, Ar-H); HRMS found: m/z 419.0367, calcd for C₁₉H₁₈NIO₂: 419.0377.

3n. 10-(4-Fluorophenyl)-3,4,6,7,10-hexahydro-1,8(2H,5H) acridinedione: mp 238-240°C; IR (KBr) 1643, 1545 cm^-1; uv (MeOH) 387 nm; flu (MeOH) 460 nm; ¹H NMR (300 MHz, CDCl₃) δ1.83 (m, 8H, =C-CH₂-CH₂), 2.35 (m, 4H, -CO-CH₂), 3.21 (s, 2H, =C-CH₂-C=), 7.19-7.32 (ABq, 4H, Ar-H); HRMS found: m/z 311.1313, calcd for C₁₉H₁₈NFO₂: 311.1317.

3o. 10-(2,5-Dimethoxy phenyl)-3,4,6,7,9,10-hexahydro-1,8(2H,5H) acridinedione: mp 248-250°C; IR (KBr) 1648, 1568 cm^-1; uv (MeOH) 380 nm; fluores (MeOH) 458 nm; ¹H NMR (300 MHz, CDCl₃) δ1.61-1.88 (m, 8H, =C-CH₂-CH_2-), 2.35 (m, 4H, -CO-CH_2-), 3.10-3.42 (dd, 2H, Jgem= 20Hz), 3.75 and 3.80 (2s, 6H, OCH₃), 6.74-6.99 (m, 3H, ArH); HRMS found: m/z 353.1610, calcd for C₂₁H₂₃NO₄: 353.1621.

3p. 10-(2-Iodophenyl)-3,4,6,7,9,10-hexahydro-1,8(2H,5H) acridinedione: mp 293-295°C; IR (KBr) 1648, 1560 cm^-1; uv (MeOH) 380 nm; fluores (MeOH) 460 nm; ¹H NMR (300 MHz, CDCl₃) δ1.60-1.88 (m, 8H, =C-CH_2-CH_2-), 2.35 (m, 4H, -CO-CH_2-), 3.16-3.33 (dd, 2H, Jgem= 20Hz), 7.16-7.98 (m, 4H, Ar-H); HRMS found: m/z 419.0867, calcd for C₁₉H₁₈NIO₂: 419.0377.

3q. 10-(2-Methoxyphenyl)-3,4,6,7,9,10-hexahydro- 1,8(2H,5H) acridinedione: mp 276-278°C; IR (KBr) 1640, 1560 cm^-1; uv (MeOH) 385 nm; fluores (MeOH) 461 nm; ¹H NMR (300 MHz, CDCl₃) δ1.73-1.98 (m, 8H, =C-CH_2-CH_2-), 2.35 (m, 4H, -CO-CH_2-), 3.06-3.41 (dd, 2H, Jgem= 20Hz), 3.88 (s, 3H, OCH₃), 7.01-7.46 (m, 4H, Ar-H); HRMS found: m/z 323.1508, calcd for C₂₀H₂₁NO₃: 323.1516.

3r. 10-(Stearyl)-3,4,6,7,9,10-hexahydro-1,8(2H, 5H) acridinedione: mp 97-99°C; IR (KBr) 1640, 1540 cm^-1; uv (MeOH) 385 nm; fluores (MeOH) 458 nm; ¹H NMR (300 MHz, CDCl₃) δ0.83 (t, 3H, -(CH₂)_17-CH₃), 1.10-1.95 (m, 32H, -(CH₂)_16-), 1.98-2.24 (m, 8H, =C-CH_2-CH_2-), 2.38 (m, 4H, -CO-CH₂), 3.04 (s, 2H, =C-CH_2-C=), 3.45 (t, 2H, N-CH₂); 13C NMR (75 MHz, CDCl₃) δ14.03, 18.21, 21.64, 22.60, 26.43, 26.52, 29.18, 29.27, 29.45, 29.52, 29.61, 31.10, 31.84, 36.03, 45.21, 113.08, 153.15, 196.24; HRMS found: m/z 469.3923, calcd for C₃₁H₅₁NO₂: 469.3907.

Results and Discussion

In the synthesis of decahydroacridines under microwave conditions, ammonium acetate, and alumina were used as supporting materials [27].  In this study, we utilized a commercially available (domestic) microwave oven to provide energy for the synthesis of various acridinediones in a solvent-free condition (without a supporting material, see Scheme I).  The tetraketones (1) were prepared from cyclohexane-1,3-dione or dimedone with various aldehydes [28,29].  Acridinediones 2a-i can be easily obtained by microwave irradiation of a mixture of the tetraketones and excess ammonium acetate or various amines in acetic acid in a domestic microwave oven for a very short time of 2~4 min (see Scheme 1).  Similarly, the acridinediones 2a-g were synthesized from xanthenes (1a).  The precursors, xanthenes (1a), were prepared from the corresponding tetraketones (1) in acetic anhydride [30] (Scheme II).  Very short time (2 min) microwave irradiation of a mixture of the xanthenes and excess of ammonium acetate results in high yields of the corresponding acridinediones (2a-g).  Various substituted acridinediones (3a-r) were synthesized by microwave irradiation, ultrasound sonication method, as well as by conventional thermal process (see Scheme III).  The experimental parameters, such as, time, microwave power, and product yields were listed in Table 2.

In ¹H NMR the C₂-CH₂ (and C₇-CH₂) is observed as singlet at 2.19 and 2.27 for the acridinediones compounds 2h and 2i, respectively.  In the case of C₄-CH₂ (and C₅-CH₂), the acridinediones 2h and 2i show geminal coupling due to the presence of substituent group at the C₉- position.  The C₉-CH₂ methylene proton appears as a singlet at ~ δ 3.1.  Geminal coupling (J= 20 Hz) of C₉-CH₂ was observed1 at δ 3.0-3.4 in compounds where the N-aryl group has one ortho substituents such as OMe and I (3o-q). 

All products were characterized by IR, ¹H-NMR, as well as high-resolution mass spectrum (HRMS).  The structure of compound 3q was unambiguously confirmed by x-ray cyrstallographic data (data not shown).  Compounds 2a-g as well as 3a~i were characterized by IR, ¹H NMR, Mass and elemental analysis, which are the same as those reported in literature [1].

The product yields and reaction conditions were listed in Table 1 & 2.  As can be seen from Table 1, two min of microwave irradiation results in very good yields in all cases.  All microwave-assisted reactions take much shorter time to reach nearly the same yields as compared to the conventional thermal methods and the ultrasonication condition.  The ultrasonication method is also significantly better than the thermal methods (based on reaction time).  Changing the substituents of the tetraketones does not seem to affect the efficiency of the microwave-assisted condensation reactions (see results in Table 1). 

Conclusion

In summary, we have reported a very short time, high yield, microwave-assisted one-pot synthesis of acridinediones.  Various acridinediones can be synthesised within 2~4 min by microwave irradiation with very good yields (80~90%) and ultrasound irradiations, as well as conventional thermal method.  The comparison of products yield, reaction time and low reaction cost for synthesis of acridinediones derivatives by using irradiation of microwave, ultrasound and conventional thermal methods are given in following order: microwave irradiation > thermal method ≅ ultrasound irradiation.

Acknowledgements

The authors are grateful to the financial support from the National Science Council, Taiwan, R. O. C. (NSC 89- 2113-M-007-054).

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Contact Details

P. Murugan

Department of Chemistry

National Tsing Hua University

Hsinchu, 30043

Taiwan

Kuo Chu Hwang

Department of Chemistry

National Tsing Hua University

Hsinchu, 30043

Taiwan

Email: [email protected]

V. T. Ramakrishnan

Department of Organic Chemistry

University of Madras

Guindy Campus

Chennai – 600 025

India

S. Balasubramanian

Department of Inorganic Chemistry

University of Madras

Guindy Campus

Chennai – 600 025

India

This paper was also published in print form in “Advances in Technology of Materials and Materials Processing”, 6[1] (2004) 37-42.