1 Introduction

Anthracene derivatives have been employed in versatile applications; for example in the organic electronics particularly organic light emitting diodes (OLED) as light-emitting materials (Varol et al., 2016; Peng et al., 2019; Chen et al., 2020) and in the chemotherapeutic field as antidepressants (Wilhelm and Schmidt, 1969; Wadler et al., 1986; Huang et al., 2002), anti-proliferative agents (Cloonan et al., 2010; Cloonan and Williams, 2011; McNamara et al., 2014), antimalarial agents (Millet et al., 2004; Henry et al., 2008) and as glucocorticoid receptor modulators (Yang et al., 2009). 9-Bromoanthracene, which serve as a precursor for the synthesis of anthracene carboxyimides, has been considered as a promising candidate for bioimaging applications (Xu et al., 2017). These compounds are soluble and stable near-infrared (NIR) dyes (Yao et al., 2009). Many compounds have been reported and synthesized starting from 9-bromoanthracene, for example a series of bidentate bis-(pyridine) anthracene isomers (2,3-PyAn, 3,3-PyAn, 2,2-PyAn) were designed as nanocrystal photosensitizer (Li et al., 2017). Additionally, 9-bromoanthracene was incorporated into deoxyadenosine to prepare fluorescent nucleotide for biological applications (Le et al., 2017) indeed, it was hybridized with fluorescein to produce chemodosimeters for detection of singlet oxygen within the live cell (Chercheja et al., 2019).

Diels-Alder (DA) cycloaddition is one of the most efficient approach for the C–C bond formation. The catalysis is one the most important variables that affect the regioselectivity of DA cycloaddition, in particular, gold catalyst creates new opportunities for the regioselective cycloaddition (Praveen, 2019). Microwave-assisted organic synthesis has been gained significant attention better than conventional method because it makes reactions faster, safer, greener, more selective and more economic (Lidström et al., 2001; Wathey et al., 2002; Praveen et al., 2013; Gawande et al., 2014). The effect of substituents at the 9- or 10-position of the anthracene on the regioselectivity and photophysical properties have been investigated (Yang and Doweyko, 2005; Kim et al., 2008; Adel and Farooqui, 2013; Mallesham et al., 2014; Zhang et al., 2017). Based on the above findings, the substituents effect of the dienophiles on the DA regioselectivity has been reported through investigation the microwave-assisted reactions of 9-bromoanthracene 1 with six dienophiles individually; acrylonitrile 2, 2-chloroacrylonitrile 3, methacryloyl chloride 4, acrylic acid 5, 1-cynao vinyl acetate 6 and phenyl vinyl sulfone 7.

2 Results and discussion

As a part of our ongoing interest in DA cycloaddition, in particular reaction of anthracene derivatives with many dienophiles (Sultan et al., 2016, 2017a, 2017b), our group has recently reported thei DA cycloaddition and tested the cycloadducts in in vitro as antidepressants (Karama et al., 2016a) and anticancer agents (Karama et al., 2016b). More recently, we reported the regioselective DA reactions between 10-allyl-1,8-dichloroanthracene and three substituted dienophiles (Sultan and Karama, 2016). Unfortunately we failed to obtain the cycloadducts in dichloromethane or toluene at room temperature. In fact, from our experiences, we can say; chlorinated anthracenes are not reactive enough for DA reactions at room temperature and even under conventional heating. In this line, the DA reaction of phenyl vinyl with sulfoxide 1,8-dichloroanthracene afford cycloadduct in 30% yield after 8 days (del Rosario Benites et al., 1999), in comparison, the reaction of phenyl vinyl sulfoxide with anthracene afford 83% of the cycloadduct (Paquette et al., 1978). So in this work, 9-bromoanthracene 1 was subjected to react with six dienophiles 2–7 separately under microwave conditions affording ortho/ meta cycloadducts with variable regioselectivity (Scheme 1, Table 1).

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Scheme 1

The DA cycloaddition of 9-bromoanthracene 1 with six dienophiles 2–7.

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The DA reaction of 9-bromoanthracene 1 with acrylonitrile 2 was successfully carried out in xylene affording two isomers ortho 8a: meta 8b in a ratio 3.5:1 respectively as deducted from nuclear magnetic resonance spectrum (NMR) of the cycloadduct crude. It looks that nitrile group as a strong EWG on the dienophile 2 exerted an electronic effect and may a slightly steric effect also leading to the formation meta 8b as a minor isomer. Meek et al, reported the DA cycloaddition of various ethylene equivalents with 9-Nitroanthracene and 9-Anthramide affording either or both isomer, the authors indicated that the negativity of the 9-substituent on the anthracene as a diene may play a significant role in determining the isomer ratio, but the negativity of the substituent on the dienophile do not (Meek et al., 1960). In a communication study, bicyclic amino acids were obtained in highly regioselectivity from DA cycloaddition of 2-acetamidoacrylate with 9-substituted anthracenes (Yang and Doweyko, 2005). This study observed that the ortho isomer was not formed at high temperatures, on the other hand, the DA cycloaddition of 2-acetamidoacrylate with 9-chloroanthracene or 9-methylanthracene were not sufficiently regioselective (Yang and Doweyko, 2005). The configuration assignment and regioselectivity of Diels-Alder cycloadducts could be clear in help of understanding the nature of the substituent (Verma and Singh, 1976, 1977). The NMR spectra of the isomer ortho 8a showed the bridge-head proton H-10 at chemical shift (δ) 4.37 ppm as triplet with coupling constants (J) 2 Hz while the corresponding bridge-head proton H-10′ of the isomer meta 8b appeared at chemical shift (δ) 4.55 ppm as doublet with coupling constants (J)2 Hz. The slight downfield shifting of the H-10′ in the isomer meta 8b, in compare to isomer ortho 8a, could be attributed to the deshielding effect of the nitrile group (CN), since its position on C-11′ is close to ^/H-10 of the isomer meta 8b.

The reaction of 9-bromoanthracene 1 with 2-chloroacrylonitrile 3 afforded almost isomer ortho 9a with insignificant amount of the isomer meta 9b. The presence chlorine atom as EWG on this dienophile 3, compare to dienophile acrylonitrile 2, exhibited an electronic effect but not steric effect, since the ratio of the isomer ortho 9a is increased. Sultan and Karama reported that chlorine atom on 2-chloroacrylonitrile had no steric effect in the DA cycloaddition of 2-chloroacrylonitrile and 10-allyl-1,8-dichloroanthracene.

The bridge-head proton H-10 of isomer ortho 9a appeared at chemical shift (δ) 4.36 ppm as a triplet with coupling constant (J) 2.4 Hz. However the amount of the isomer meta 9b was insignificant, the assignment of this isomer was scientifically valuable; the bridge-head proton H-10′ of the isomer meta 9b appeared at chemical shift (δ) 4.72 ppm as a singlet signal. The shifting of H-10′ of the isomer meta 9b, in relative to H-10 of the isomer ortho 9a, could be attributed to the deshielding effect of the chlorine (Cl) atom and nitrile group (CN), since their positions on C-11′ are very close to H-10′.

In contrast, the isomer meta 10b was the major resulting from the reaction of 9-bromoanthracene 1 with 1-cynao vinyl acetate 4. NMR assignment was recruited to understand the regioselectivity and then identify the isomers and their ratio. It’s clear that acetate group on the dienophile exerted a significant steric or/and electronic effects leading to the formation isomer meta 10b as a major in a ratio 1:4 for ortho 10a: meta 10b respectively as deducted from NMR spectrum of the cycloadduct crude. For these cycloadducts; the bridge-head proton H-10′ of isomer meta 10b appeared at chemical shift (δ) 5.07 ppm as a singlet while the bridge-head proton H-10 of the isomer ortho 10a appeared at chemical shift (δ) 4.37 ppm as triplet with coupling constants (J) 2.8 Hz. The downfield shifting of the H-10′ in the isomer meta 10b, in compare to isomer ortho 10a, could be attributed to the deshielding effect of the nitrile (CN) and acetoxy (OAc) groups, since their positions on C-^/11 are close to H-10′ of the isomer meta 10b.

The DA cycloaddition of 9-bromoanthracene 1 with acrylic acid 5 was carried out under the same condition to its reaction with acrylonitrile 2 and the ratio isomers ortho 11a: meta 11b was in the same direction where isomer ortho 11a is the major. But the amount of isomer ortho 11a is less and vice versa regarding amount of isomer meta 11b. This is could be referred to the steric effect exerted by carboxyl group (COOH) that is more than nitrile group (CN) do. The isomers ortho 11a: meta 11b ratio is 1.3:1 while it was 3.5:1 in case of acrylonitrile. The NMR spectra of the isomer ortho 11a exhibited the bridge-head proton H-10 at chemical shift (δ) 4.39 ppm as broad singlet and after enlarge the spectra it appears as triplet with coupling constants (J) 2.4 Hz while the bridge-head proton H-10′ of the isomer meta 11b appeared at chemical shift (δ) 4.74 ppm as doublet with coupling constants (J) 2 Hz. The slight downfield shifting of the H-10′ in the isomer meta 11b, in compare to isomer ortho 11a, is may due to the deshielding effect of the carboxyl group (COOH), since its position on C-11′ is close to H-10′ of the isomer meta 11b.

The effect of methyl group as an electron donating group (EDG) beside to an electron withdrawing group (EWG) on the dienophile, as in methacryloyl chloride 6, is studied. The DA cycloaddition of 9-bromoanthracene 1 with methacryloyl chloride 6 led to the formation isomers ortho 12a and meta 12b in a ratio 2:1 respectively. The ¹H NMR spectrum was employed to distinguish between the isomers ortho 12a and meta 12b; the bridge-head proton H-10 of the isomer ortho 12a appeared as a triplet at chemical shift (δ) 4.29 ppm with coupling constants (J) 2.4 Hz whereas the corresponding bridge-head proton H-10′ of isomer meta 12b appeared as singlet signal at chemical shift (δ) 4.42 ppm.

Herein, we also report the DA cycloaddition, where the only isomer meta 13b was formed. The DA cycloaddition of 9-bromoanthracene 1 with phenyl vinyl sulfone 7 gave only isomer meta 13b. However, the phenyl sulfone group is EWG, the big significant volume of the phenyl sulfone group exhibited a significant steric effect leading to no formation of the isomer ortho 13a but only isomer meta 13b. The assignment of the isomer meta 13b by ¹H NMR analysis was clear. The bridge-head proton H-10′ of the isomer meta 13b exhibited as a doublet signal and appeared at chemical shift (δ) 4.91 ppm with coupling constants (J) 1.6 Hz.

3 Conclusion

In conclusion, microwave-assisted DA cycloadditions of 9-Bromoanthracene 1 with six different-substituted dienophiles 2–7 have been reported. The ortho 8a-13a and meta 8b-13b cycloadducts–were obtained in different ratios. The dienophiles; acrylonitrile 2, 2-chloroacrylonitrile 3, methacryloyl chloride 4 and acrylic acid 5 were independently reacted with 9-bromoanthracene 1 affording ortho 8a-11a as major isomers while dienophile 1-cynao vinyl acetate 6 was reacted with 9-bromoanthracene 1 affording meta 12b as a major isomer. In contrast, the dienophile phenyl vinyl sulfone 7 was reacted with 9-bromoanthracene 1 affording only isomer meta 13b. It is noteworthy to mention that the steric or/and electronic nature of the dienophile substituent is/are playing significant roles in the regioselectivity and isomers ratio.

Funding

King Saud University-Researchers Supporting Project Number (RSP-2020/64).