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Photocatalytic Potency of Ruthenium Polypyridyl Complex and Eosin Y for the Effective Development of C-C and C-S Bond: A Correlative Analysis.

Byline: Fouzia Abdul Sattar, Fayaz Ahmed, Rongmin Yu, Mohammad Ayaz Khan Malghani and Canzhong Lu

Summary: The photochemical transformations have gained widespread recognition in the recent years because of the generally mild reaction conditions needed for substrate activation, ideally the light alone and their appropriateness for green reactions. A variety of catalyst systems have been developed for visible light driven reactions. The unprecedented [Ru(bpy)3]2+ complexes as well as xanthene based organic dyes has gained widespread recognition due to their effectiveness and broad applications in organic synthesis. The Photoredox catalyst based on transition metal complexes or organic dyes have comparable redox abilities but each system has its own distinctive benefits.

In this perspective photocatalytic efficacy of organometallic ruthenium and eosin Y have been investigated in connection to their pursuit for the photocatalytic oxidative coupling of N-aryl tetrahydroisoquinoline with carbon and sulfur containing nucleophiles. The eosin Y confirmed to be more efficient in our studies. The photophysical properties and reaction mechanism of both types of catalysts are well established in the literature.

Key Words: Photoredox catalyst, Tris (bipyridine) ruthenium (II) chloride, Eosin Y, Tetrahydroisoquinoline


The isoquinoline alkaloids are widely distributed in the realm of flora and fauna, and have gained significant consideration on account of their enormous biological activities [1]. Among them the 1,2,3,4-tetrahydroisoquinoline component is extensively ascertained in biologically active molecules of both natural and synthetic origin, making its derivatives as the promising candidates for drugs [2]. In organic synthesis C-H bond activation through direct functionalization of nitrogen heterocycles represents an efficient regioselective method leading to variety of substituents with diverse functional groups onto the heterocycle system [3-6]. Notably, this procedure is preferred owing to the facile oxidation of tertiary amines that form highly reactive iminium ion intermediates for further functionalization including the development of carbon-carbon or carbon-heteroatom bonds [7].

Over the past 20 years, there has been a great deal of efforts made in order to achieve C-H bond functionalization adjoining tertiary nitrogen atom [8]. Numerous esteemed methods for oxidative coupling of tertiary amines with a range of nucleophiles have been developed by metallic catalytic systems [9] metal free catalysis [10] and in conjunction with visible light photoredox catalyst [11]. In the recent reports visible light photoredox catalysis has been ascertained as a unique method for the a- functionalization of tertiary amines offering various inter and intra molecular transformations at milder condition [12-15].Various photochemical processes that are mediated by organometallic complexes or organic dye based photocatalysts have received increasing attention due to recent endeavors in organic synthesis [16].

Despite the major research focus on visible light mediated formation of carbon hetero atom bonds, the effective development of C-S bonds is still challenging area with respect to the corresponding C-O and C-P coupling reactions [17, 18], since a significant number of bioactive molecules comprise sulfur as an essential component in their structural diversity [19].

Keeping in view the identical photochemical properties of organic dyes and transition metal complexes in various synthetic transformations [20], the present studies describes the photocatalytic efficiency of ruthenium tris-(bipyridine) chloride and eosin Y for the facile construction of C-C and C-S bonds employing the N-aryl tetrahydroisoquinolines as the target substrates.



All the chemicals were purchased from Sigma-Aldrich and Tokyo Chemical Industries and were used without further purification, unless otherwise specified. Experiments were conducted at ambient temperature, unless noted otherwise. Petroleum ether refers to the fraction boiling between 60 - 80 oC. The brine was saturated. The chromatographic stationary phase was silica gel. Organic extracts were dried over Na2SO4 and filtered. Solvents were evaporated under reduced pressure. The 1H NMR experiments were performed on Varian INOVA operating at 400 MHz in deuterochloroform solution, except where noted. Spectra were referenced to residual solvent peaks. Chemical shifts are stated in ppm and coupling constants (J) are reported in Hz. EI-MS spectra were recorded on Finnigan DECAX -3000 LCQ deca XP ion trap mass spectrometer. N- Aryl tetrahydroisoquinolines were synthesized by the reported method [21].

General Procedure for Photocatalytic Coupling Reaction Via Ruthenium Metal Complex.

In a 10 mL round bottom flask furnished with magnetic stir bar was charged with tris (bipyridine) ruthenium (II) dichloride (1mol %) respective tetrahydroisoquinolines 1 and 1a (0.11 mm, 1 equiv. each), Cuprous cyanide (1.2 equiv.) and Acetic acid (5.0 equiv. for cyanation only) were dissolved in DMF (2.5 mL). The mixture was irradiated by a 7 W fluorescent bulb (2U Electronic CFL, distance app. 5 cm) for the time indicated. The reaction was monitored via TLC (petroleum ether: ethylacetate). Upon consumption of starting materials, the crude mixture was poured into water (10 ml) and extracted with ethylacetate (3x7 ml). The combined organic layers were washed with brine (7 ml), and then dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by column chromatography over silica gel using petroleum ether/ethylacetate to afford the desired products in good to excellent yield.

General Procedure for Eosin Y Photocatalyzed Oxidative Coupling Reaction

To a flame dried 10 mL round bottom flask equipped with a magnetic stir bar were added the subsequent tetrahydroisoquinolines 1 and 1a (0.25mm, 1 equiv.) eosin Y (2 mol %) and all were dissolved in DMF (0.25 mmol/mL). Cuprous cyanide (1.5 equiv.) was added and the resulting mixture was irradiated through the bottom side of the flask using 7 W fluorescent bulb. After the reaction was completed (as judged by the TLC) the mixture was transferred to separating funnel, diluted with diethyl ether and washed with water (3x10 ml). The aqueous phase was extracted three times with diethyl ether.

The combined organic layers were dried over anhydrous Sodium sulfate, filtered and concentrated in vacuum. Purification of the crude product was achieved by silica gel column chromatography applying petroleum ether/ethylacetate.

2-phenyl-1,2,3,4-tetrahydroisoquinoline-1- carbonitrile (3) White solid; isolated Yield (ruthenium metal complex 85%, eosin Y 90%); Mp: 100-101degC. 1H NMR (400 MHz, CDCl3): d 7.21- 7.37(m, 6H), 7.08- 6.98 (m, 3H), 5.50(s, 1H), 3.74- 3.77(m, 1H), 3.43-3.53(m, 1H), 3.11-3.18 (m, 1H), 2.93-2.97 (m, 1H); 13C NMR (100MHz, CDCl3): d 148.3, 134.5, 129.5, 129.3, 128.7, 127.0, 126.8, 121.8, 117.7, 117.5, 53.1, 44.1, 28.5; IR (KBr): 2221 (CN), 1680 (C=C), 1498, 1029, 744, 693; MS (m/z): 234(M+)100%), 208 ([M-CN]+, 27%).

2-(4-methoxyphenyl)-1,2,3,4- tetrahydroisoquinoline-1-carbonitrile (3a) Yellow solid; isolated Yield (ruthenium metal complex 77%, eosin Y 85%); Mp: 106-107 degC. 1H NMR ( 400 MHz, CDCl3): d 7.22-7.31 (m, 4H), 7.09 (d, J = 6.8 Hz, 2H), 6.92 (d, J = 5.6 Hz, 2H), 5.30 (s, 1H), 3.80 (s, 3H), 3.50-3.60 (m, 1H), 3.40-3.50 (m, 1H), 3.12-3.21 (m, 1H), 2.91-2.96 (m, 1H); 13C NMR (100MHz, CDCl3): d 155.7, 142.6, 134.3, 129.7, 128.6, 127.0, 126.7, 121.0, 117.6, 114.8, 55.6, 55.5, 44.9, 28.7; IR (KBr): 2182 (CN), 1512, (C=C), 1247 (C-O); MS (m/z): 264(M+) 58%), 238 ([M-CN]+ 16%).

2-phenyl-1,2,3,4-tetrahydroisoquinoline-1- thiocarbonitrile (4): colorless crystalline solid; isolated Yield (ruthenium metal complex 83%,eosin Y 86%); Mp: 102-103 degC; 1H NMR (400 MHz, CDCl3): d 7.22-7.37(m, 6H), 7.09- 6.99 (m, 3H), 5.50(s, 1H), 3.76-3.74(m, 1H), 3.44-3.51(m, 1H), 3.12-3.15 (m, 1H), 2.94-2.99 (m, 1H); 13C NMR (100 MHz, CDCl3): d 148.3, 134.6, 129.6, 129.5, 128.7, 127.0, 126.8, 121.8, 117.7, 117.6, 53.1, 44.2, 28.5; IR (KBr): 2170 (SCN), 1531(C=C) ; MS (m/z): 266(M+),100%),208 ([M-SCN]+, 21%).

2-(4-methoxyphenyl)-1,2,3,4- tetrahydroisoquinoline-1- thiocarbonitrile (4a): Grey solid; isolated Yield (ruthenium metal complex 88%,eosin Y 95%); Mp: 105-106degC; 1H NMR (400 MHz,CDCl3): d 7.22-7.31 (m, 4H), 7.09 (d, J = 6.8 Hz, 2H), 6.92 (d, J = 5.6 Hz, 2H), 5.30 (s, 1H), 3.80 (s, 3H), 3.50-3.60 (m, 1H), 3.40-3.50 (m, 1H), 3.12- 3.21 (m, 1H), 2.93-2.96 (m, 1H); 13C NMR (100MHz, CDCl3): d 155.7, 142.6, 134.3, 129.7, 128.6, 127.0, 126.7, 121.0, 117.6, 114.8, 55.6, 55.5, 44.9, 28.7; IR (KBr): 2182(SCN), 1510 (C=C), 1257 (C-O); MS (m/z): 297 (M+) 61%), 239 ([M-SCN]+ 23%).

Result and Discussion

Preparation of Compounds 3, 3a, 4 and 4a

The initial studies commenced on the oxidative coupling of two N-aryl (N-Phenyl and N- paramethoxyphenyl) tetrahydroisoquinolines 1and1a as the model substrates with CuCN employing the ruthenium tris-(bipyridine) chloride as photocatalyst under mild and aerobic reaction conditions reported by Rueping and co- workers [22]. The optimal yield was attained when the metal catalyst was applied in DMF under 7 W fluorescent bulb instead of 5 W fluorescent bulb for 16 and 18 h respectively. In accordance with their results the corresponding cyanation products 3 and 3a were obtained in 85 and 77 % yield (Table 1, entries 2, 4). The mild alteration in the resulting yield may be reasoned due to the limited variations in reaction parameters.

Table-1: Tris (bipyridine) ruthenium (II) dichloride Catalyzed Oxidative Addition of Cyano and


Entry###Ar###Conditions a###Product b


###1###Ph###X=CN, THF, ACOH, 12 h###3###64

###2###Ph###X=CN,DMF, ACOH, 16 h###3###85

###3###4-OMePh###X=CN, THF, ACOH, 12 h###3a###68

###X=CN, DMF, ACOH, 18



###5###Ph###X=SCN, THF, 12 h###4###75

###6###Ph###X=SCN, DMF, 16 h###4###83

###7###4-OMePh###X=SCN, THF, 12 h###4a###70

###8###4-OMePh###X=SCN, DMF, 18 h###4a###88

Since the sulfur bearing organic compounds are regarded as important leads and building blocks for many synthetic and natural products, so there is an urgent need for their facile preparation [23].Therefore by utilizing the subsequent reaction conditions for cyanation, the desired coupling products 4 and 4a were obtained in 83 and 88 % isolated yields after irradiation for 16 and 18 h respectively (Table 1, entries 6, 8). Subsequently the DMF proved to be the preferred solvent in current studies (Table 1, entries 2, 4, 6, 8). To further examine the outcomes of visible light-induced oxidative coupling strategy, the photocatalyst was switched to eosin Y confining 1 and 1a as the representative substrates. In recent studies conducted by various groups [20, 24] eosin Y has affirmed to be the most comprehensive photoredox catalyst on account of its high visible-light absorption, favorable redox properties and economic advantage over metal catalysts [25].

The desired transformations were investigated using the conditions reported by Konig [26], by coupling the substrates 1 and 1a with the inorganic cyano group using CuCN surprisingly, contrary to the results revealed by Konig, a marked improvement in the isolated yields (90 and 85 %) were observed following the 18 and 20 h of irradiation under 7 W fluorescent bulb (Table 2, entries 2, 4).

Table-2: Oxidative Coupling of Cyano and Thiocyano nucleophiles with Tetrahydroisoq-

Entry###Ar###Conditions a###Product b###Yield (%) c

1###Ph###X=CN, THF,10 h###3###55

2###Ph###X=CN, DMF,18 h###3###90

3###4-OMePh###X=CN, THF,10 h###3a###59

4###4-OMePh###X=CN, DMF 20 h###3a###85

5###Ph###X=SCN, THF,10 h###4###60

6###Ph###X=SCN, DMF, 18 h###4###86

7###4-OMePh###X=SCN, THF,10 h###4a###59

8###4-OMePh###X=SCN, DMF, 20 h###4a###95

The mild deviation from the illustrated results is anticipated due to minor variation in reaction parameters particularly the use of CuCN instead of malononitrile that appeared to be a superior nucleophile in DMF on prolong irradiation. With the striking outcome of cyanation, the method was further extended to the coupling of SCN nucleophile to our representative substrates 1 and 1a and it was examined that the reactions were found to give consistent results with our previous investigations. (Table 2, entries 6, 8) Following the successful optimization of reaction conditions, the reaction was designed on gram scale for the preparation of 4a to reveal the synthetic utility of this process. Fortunately, the reaction continued smoothly to furnish the corresponding product in 83% yield after 30 h. The positive results revealed the extended efficiency of the reactions performed via inexpensive organic dye catalyst symbolizing the preferred alternate to metal complex catalyst.


The photredox catalyst has received ample attention from the scientific community due to its broad application, mild reaction conditions and greener approach proving it to be superior alternate to existing catalytic systems. The current studies revealed that with the eosin Y, the reaction proceeded efficiently and provided the desired coupling products in significant yield; further a new C-S bond formation method using eosin Y has also been established. Concomitant studies are underway for the extension of eosin Y for the design and development of new C-H activation reactions primarily for C-S bond construction under sustainable conditions.


The author is thankful to the Third world Academy of Sciences for providing the fellowship.


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Author:Sattar, Fouzia Abdul; Ahmed, Fayaz; Yu, Rongmin; Malghani, Mohammad Ayaz Khan; Lu, Canzhong
Publication:Journal of the Chemical Society of Pakistan
Article Type:Report
Date:Aug 31, 2016
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