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Reactions of 2,3-naphthalenediol with cyclohexane in the presence of aluminum halides
Tetrahedron Letters 56 (2015) 2254–2257
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Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Reactions of 2,3-naphthalenediol with cyclohexane in the presence of aluminum halides Zhongwei Zhu a,b, Ludmila A. Ostashevskaya a, Konstantin Yu. Koltunov a,c,⇑ a
Novosibirsk State University, Pirogova, 2, Novosibirsk 630090, Russia Heilongjiang University, Xue Fu Road, No. 74, Nan-gang, Harbin 150080, PR China c Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, Pr. Akademika Lavrentieva, 5, Novosibirsk 630090, Russia b
a r t i c l e
i n f o
Article history: Received 28 January 2015 Revised 10 March 2015 Accepted 13 March 2015 Available online 19 March 2015 Keywords: Naphthols Superacids Superelectrophiles Ionic hydrogenation
a b s t r a c t 2,3-Naphthalenediol (7) undergoes selective ionic hydrogenation with cyclohexane in the presence of excess AlCl3 or AlBr3 to afford 5,6,7,8-tetrahydro-2,3-naphthalenediol (8). Compound 8 can be further converted into 5,6,7,8-tetrahydro-1,2-naphthalenediol (9) and pyrocatechol (10). The discovered reactions represent new and efficient synthetic approaches to produce difficult to obtain derivatives of 7. The mechanistic aspects of the reactions, and the potential involvement of superelectrophilic dicationic intermediates, are discussed. Ó 2015 Elsevier Ltd. All rights reserved.
Introduction It is known that 1- and 2-naphthols react with benzene and other arenes under the influence of an excess of aluminum halides, HUSY-zeolites or in the HF–SbF5 superacid medium to give 4-aryl-1- and 4-aryl-2-tetralones (structures 1 and 2, respectively, Scheme 1).1 In addition, naphthols undergo selective ionic reduction by alkanes under similar reaction conditions to offer 1- and 2-tetralones (structures 3 and 4, Scheme 1).2 The mechanism of these reactions was recognized to involve superelectrophilic3 dications 5 and 6 as the key intermediates formed by C,C-diprotonation. A number of such dications have indeed been generated as long-lived species by dissolving naphthols and their derivatives in liquid superacids.4 Furthermore, some isomeric naphthalenediols have been shown to react with benzene, o-dichlorobenzene and cyclohexane by analogy with the parent naphthols to afford the corresponding hydroxy tetralones (Scheme 2).1c,e,5 On the other hand, 1,4-naphthalenediol has proved to be totally inert toward benzene and cyclohexane under the same reaction conditions.1b,2a In a continuation of our interest in the superelectrophilic activation of naphthols1,2,4,5 and their heterocyclic analogues,6 a study on the reactivity of 2,3-naphthalenediol (7) with cyclohexane is reported herein with the aim of discovering new synthetic
⇑ Corresponding author. Tel.: +7 383 326 9765; fax: +7 383 330 8056. E-mail address: [email protected] (K.Yu. Koltunov). http://dx.doi.org/10.1016/j.tetlet.2015.03.059 0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
OH
O
O
ArH (AlkH) strong acid
3
1 Ar OH ArH (AlkH)
O
O
strong acid
4
2 Ar + O X
+ O X
key intermediates: +
5
+
6
_ _ X = H or AlnCl3n or Aln Br3n
Scheme 1. Reactions of naphthols with arenes (ArH) and alkanes (AlkH).
approaches to naphthol derivatives. The latter are generally considered as important intermediates for medicinal chemistry and other practical applications.1e,5b The main aim of the work was also to determine the regioselectivity of any potential reactions. Results and discussion Diol 7 was found to react smoothly with cyclohexane in the presence of a 5-fold molar excess of AlBr3 or AlCl3 to give a mixture of products including 5,6,7,8-tetrahydro-2,3-naphthalenediol (8),
2255
Z. Zhu et al. / Tetrahedron Letters 56 (2015) 2254–2257 OH HO
HO
OH
OH
+ HO
HO
AlBr3 or AlCl3 1,5-, 1,6- and 1,7-diols OH
O
O
ArH (cyclo-C6H12)
11
Ar
OH
O HO
O HO
OH
X O
+
H
H
+
13
AlBr3 or AlCl3 2,6- and 2,7-diols
12
X O
ArH (cyclo-C6H12)
+
OH
14
OH
+ +
OH
15
OH
_ _ X = H or AlnCl3n or AlnBr3n
Ar
Scheme 2. Reactions of naphthalenediols with arenes (ArH) and cyclohexane. Scheme 4. Reaction intermediates proposed.
5,6,7,8-tetrahydro-1,2-naphthalenediol (9), and pyrocatechol (10) (Scheme 3, Table 1). The selectivity of this reaction is strongly dependent on the reaction conditions. Thus, 7 reacts slowly with cyclohexane in an AlBr3–CH2Br2 acid system at room temperature to offer 8 as the major product (Table 1, entry 1). The same reaction proceeds more readily in the presence of AlCl3 at elevated temperature (110 °C, pressure tube) in the absence of solvent to afford 8 in 90% yield after only 10 min (Table 1, entry 2). The latter procedure can be considered as an efficient and convenient synthetic approach for the selective partial hydrogenation of 7 to 8. Upon increasing the reaction time, conversion of 7 into 9 was observed to occur after 15–60 min using the same conditions (Table 1, entries 3–5). Further increases of the reaction time resulted in an increase in the amount of 10 (Table 1, entries 6–8). Therefore, products 9 and 10 are derived from 8 as a result of further transformations. It is evident that the reduction of 7 to 8 proceeds via a quite different reaction mechanism compared to that of 1- and 2-naphthols, which react with alkanes and arenes at their phenolic ring (Scheme 1). Conversely, electrophilic activation of 7 is achieved through the protonation of its benzene ring. In principle, both the C5(8)- and C6(7)-atoms of 7 can be protonated to form ions 11 and 12, respectively (Scheme 4). However, monocationic species such as 11 and 12 may not be electrophilic enough to react with cyclohexane.6a Most likely, dicationic species 13–14 are the true reactive intermediates (Scheme 4). The analogous O,Cdiprotonation has been demonstrated earlier for 2-naphthol when dissolved in the HF–SbF5–SO2ClF superacid system at
OH OH
7
OH
OH
cyclo-C6H12
+
acid 8
OH
OH OH +
9
OH
10
Scheme 3. Reaction of 7 with cyclohexane in the presence of aluminum halides (for reagents and conditions see Table 1).
Table 1 Reactions of 7 with cyclohexane (30 equiv)
a
Entry
Acid, conditions
Molar ratio 8:9:10a
1 2 3 4 5 6 7 8 9 10
AlBr3 (5 equiv) CH2Br2, 25 °C, 24 h AlCl3 (5 equiv), 110 °C, 10 min AlCl3 (5 equiv), 110 °C, 15 min AlCl3 (5 equiv), 110 °C, 30 min AlCl3 (5 equiv), 110 °C, 1 h AlCl3 (5 equiv), 110 °C, 3 h AlCl3 (5 equiv), 110 °C, 5 h AlCl3 (5 equiv), 110 °C, 10 h AlCl3 (3 equiv), 110 °C, 1 h AlCl3 (1.5 equiv), 110 °C, 1 h
90:7:3 90:5:5 21:64:15 21:61:18 20:56:24 33:34:33 44:13:43 27:9:64 90:8:2b 90:8:2c
Complete conversion of 7 was achieved. The ratio given is based on 1H NMR spectroscopic data. b Conversion of 7 is approximately 30%. c Conversion of 7 is <5%.
80 °C, which is in contrast to the formation of 6 (X = H) in the same acid at 40 °C.4b Notably, such an activation of the benzene rather than phenolic moiety is more typical for N-heterocyclic derivatives of 2-naphthol and their reactions with benzene and cyclohexane.7 Generation of C,C-diprotonated species 15 could be an additional way of (super)electrophilic activation of 7 (Scheme 4). It should be noted that intermediates 13 and 14 may be additionally O-protonated/coordinated at the intact hydroxyl group. This will increase the electrophilicity of these species even further. A catalytic amount of protic superacid (HHal–AlnHal3n or H2O–AlnHal3n), which is required for the generation of 13–15, is normally present in such reaction media due to the presence of traces of water in the starting materials. The acid strength of HHal–AlnHal3n (Hal = Br, Cl) is estimated to be 15 to 18 on the HO scale.8 Scheme 5 represents a probable reaction mechanism for the conversion of 7 into 8 involving the likely intermediacy of 13. According to Scheme 5, intermediate 13 undergoes selective hydrogenation with cyclohexane to give intermediate 16, which undergoes additional protonation followed by reaction with a second molecule of cyclohexane. Under the reaction conditions cyclohexane exists in equilibrium with methylcyclopentane.9 Both cyclohexane and methylcyclopentane can convert into isomeric cations C6H+11, which in turn react with an excess of cyclohexane/methylcyclopentane to give isomeric C6H11–C6H11 alkanes (C6H11 = cyclohexyl, methylcyclopentyl; NMR and GC–MS data). These hydrocarbons are considered as the final oxidation product in such reactions.10 The conversion of 8 into 9 most probably proceeds through an electrophilic transalkylation mechanism (Scheme 6). The key intermediate in this case could be O,C-diprotonated/coordinated species 17. Since the loss of a primary carbocation from an arenium ion has not yet been properly ascertained,11 the formation of intermediate 18 seems highly unlikely, and rearrangement occurring through the spirocyclic intermediate 19 can thus be suggested (Scheme 6). Indeed, the acid-catalyzed intramolecular isomerization of xylenes and diethylbenzenes occurs predominantly via 1,2-bond migrations.12 It is remarkable that primary carbocations 18 (if they were generated) do not rearrange into more stable derivative 20 before cyclization to give the expected products 21 and 22 (Scheme 7). Presumably, the phenol moiety in 20 is deactivated by O-coordination with AlHal3 and does not react with the adjacent secondary carbocation center. On the other hand, the absence of compounds
13
+ X O H
cyclo -C6H12 -C6H11+
16
H+, cyclo-C6H12 -C6 H11+
8
-X+ _ _ X = H or AlnCl3n or AlnBr3n
OH
Scheme 5. Proposed mechanism for the reduction of 7 to 8.
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Z. Zhu et al. / Tetrahedron Letters 56 (2015) 2254–2257
8
+ H O X + OH
X+, H+
17
superelectrophilic intermediates. This is in contrast to the regioselectivity shown in similar reactions for the parent 2-naphthol and isomeric 2,6- and 2,7-naphthalendiols.1,2,5 From a practical viewpoint, diol 7 is efficiently modified into difficult to obtain15 derivatives 8 and 9 using simple procedures and readily available reagents.
+ H O X +
OH
1,2-shift + X O H
+
OH
18
19
+ X O H + OH
OH
Experimental 5,6,7,8-Tetrahydro-2,3-naphthalenediol (8)
+ H O X +
OH
1,2-shift + H O X + OH
-X+, -H+
9
+ H O X
+
-X+, -H+
_ _ X = H or AlnCl3n or AlnBr3n
Scheme 6. Proposed mechanisms for the conversion of 8 into 9.
18
~ H+
OH
+ X O H
+
20 _ X = H or Aln Cl3n
OH _ or AlnBr3n
OH
OH +
21
OH
22
not observed
Scheme 7. A possible, but not observed reactivity of 18.
21 and 22 among the reaction products is in line with the proposed limited contribution of 18 in the conversion of 8 to 9. Finally, the formation of 10 can be explained by complete dealkylation of 8 and 9 under the highly acidic conditions. Generation of partially dealkylated intermediates 18 and 20 can be considered as an initial step in such a reaction pathway, while the absence of 21 and 22 in the reaction mixtures may be related to their rapid dealkylation to 10. The latter possibility is in agreement with relatively smooth dealkylation of 4-cyclohexylpyrocatehol in the presence of excess AlBr3.13 Alternatively, more sophisticated reaction mechanisms, such as those suggested earlier for intermolecular transalkylation–dealkylation in ethylbenzene (with the exception of the intermediacy of a primary carbocation),11,12b can explain the formation of catechol 10. It is worth noting that tetralin (a close analogue of 8 and 9) also undergoes dealkylation in the presence of AlCl3 at 110 °C.14 However, this reaction is rather unselective and gives benzene along with a large variety of alkylated products. It should be also noted that a 5-fold molar excess of aluminum halides is not essential and a decrease in the loading is possible (Table 1, entries 9 and 10). This, however, slows down the reaction. Moreover, the use of less than a 1.5-fold molar excess of AlCl3 or AlBr3 completely suppresses the reaction. Clearly, the excess of aluminum halide provides an acid strength sufficient to form dicationic intermediates such as 13–15 and 17. Conclusions The model reactions shown with cyclohexane demonstrate the activity and regioselectivity patterns of the current synthetic approach (superelectrophilic activation with an excess of aluminum halides) toward diol 7. It has been shown that the reagents react exclusively with the benzene ring in 7, which is most plausibly interpreted in terms of key O,C-diprotonated/coordinated
A mixture of 7 (1.0 g, 6.25 mmol), AlCl3 (4.2 g, 31.5 mmol), and cyclohexane (20 mL) was stirred in a 100 mL Ace pressure tube at 110 °C (oil bath temperature) for 10 min, followed by cooling and pouring the mixture onto several grams of ice. The resulting mixture was extracted with Et2O. The organic phase was washed with water, dried over anhydrous MgSO4, and concentrated in vacuo to give a mixture of 8, 9, and 10 and isomeric C12H22-alkanes in 18:1:1:40 molar ratio (1H NMR and GC–MS data). The mixture was separated by flash column chromatography with benzene– acetone (5:1) to give diol 8 (0.78 g, 76%). Mp 126–129 °C, lit.15b Mp 127–130 °C. 1H NMR (500 MHz, CDCl3) d 1.72–1.79 (m, 4H), 2.61–2.69 (m, 4H), 5.02 (br s 2H), 6.58 (s, 2H). 13C NMR (125 MHz, CDCl3) d 23.4, 28.9, 115.8, 129.8, 141.4. GC–MS [M]+: 164. 5,6,7,8-Tetrahydro-1,2-naphthalenediol (9) A mixture of 7 (0.2 g, 1.25 mmol), AlCl3 (0.83 g, 6.2 mmol), and cyclohexane (5 mL) was stirred in a 15 mL Ace pressure tube at 110 °C for 15 min to provide, after usual workup, the crude product (mixture of 8, 9, 10 in 21:64:15 molar ratio and C12H22-alkanes), which was separated by flash column chromatography with benzene–acetone (5:1) to give compound 9 (0.12 g, 58%). 1H NMR (500 MHz, CDCl3) d 1.72–1.78 (m, 2H), 1.78–1.84 (m, 2H), 2.66 (t, J 6.5 Hz, 2H), 2.69 (t, J 6.5 Hz, 2H), 5.17 (br s 2H), 6.55 (d, J 8 Hz, 1H), 6.66 (d, J 8 Hz, 1H). 13C NMR (125 MHz, CDCl3) d 22.7, 23.10, 23.13, 29.2, 112.7, 120.8, 124.2, 130.7, 140.6, 141.6. GC–MS [M]+: 164. Pirocatechol (10) A mixture of 7 (0.2 g, 1.25 mmol), AlCl3 (0.83 g, 6.2 mmol), and cyclohexane (5 mL) was stirred in a 15 mL Ace pressure tube at 110 °C for 10 h to afford, after usual workup and chromatographic purification, compound 10 (0.063 g, 46%). 1H NMR (500 MHz, CDCl3) d 5.05 (br s 2H), 6.78–6.88 (m, 4H). 13C NMR (125 MHz, CDCl3) d 115.7, 121.4, 143.7. GC–MS [M]+: 110. Acknowledgments We thank the reviewers for their helpful and constructive comments. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.03. 059. References and notes 1. (a) Methoden der Organischen Chemie; Thomas, H. G., Ed.; Thieme: Stuttgart, 1976; Vol. 7, p 1710. 2b; (b) Repinskaya, I. B.; Koltunov, K. Yu.; Shakirov, M. M.; Shchegoleva, L. N.; Koptyug, V. A. Russ. J. Org. Chem. 1993, 29, 803–810; (c) Koltunov, K. Yu.; Repinskaya, I. B.; Shakirov, M. M.; Shchegoleva, L. N. Russ. J.
Z. Zhu et al. / Tetrahedron Letters 56 (2015) 2254–2257
2.
3. 4.
5.
6.
7.
Org. Chem. 1994, 39, 88–96; (d) Koltunov, K. Yu.; Walspurger, S.; Sommer, J. Chem. Commun. 2004, 1754–1755; (e) Koltunov, K. Yu.; Chernov, A. N.; Prakash, G. K. S.; Olah, G. A. Chem. Pharm. Bull. 2012, 60, 722–727; (f) Koltunov, K. Yu.; Chernov, A. N.; Ostashevskaya, L. A.; Gribov, P. A. Mendeleev Commun. 2014, 24, 122–124. (a) Koltunov, K. Yu.; Subbotina, E. N.; Repinskaya, I. B. Russ. J. Org. Chem. 1997, 33, 689–693; (b) Koltunov, K. Yu.; Ostashevskaya, L. A.; Repinskaya, I. B. Russ. J. Org. Chem. 1998, 34, 1796–1797; (c) Koltunov, K. Yu.; Walspurger, S.; Sommer, J. J. Mol. Catal. A 2006, 245, 231–234. Olah, G. A.; Klumpp, D. A. Superelectrophiles and Their Chemistry; Wiley: New York, 2008. (a) Repinskaya, I. B.; Shakirov, M. M.; Koltunov, K. Yu.; Koptyug, V. A. J. Org. Chem. USSR 1988, 24, 1719–1727; (b) Repinskaya, I. B.; Koltunov, K. Yu.; Shakirov, M. M.; Koptyug, V. A. J. Org. Chem. USSR 1992, 28, 785–793. (a) Ostashevskaya, L. A.; Koltunov, K. Yu.; Repinskaya, I. B. Russ. J. Org. Chem. 2000, 36, 1474–1477; (b) Koltunov, K. Yu. Tetrahedron Lett. 2008, 49, 3891– 3894. (a) Koltunov, K. Yu.; Prakash, G. K. S.; Rasul, G.; Olah, G. A. J. Org. Chem. 2002, 72, 4330–4336; (b) Koltunov, K. Yu.; Prakash, G. K. S.; Rasul, G.; Olah, G. A. J. Org. Chem. 2007, 72, 7394–7397. and references cited therein. (a) Koltunov, K. Yu.; Prakash, G. K. S.; Rasul, G.; Olah, G. A. J. Org. Chem. 2002, 67, 8943–8951; (b) Koltunov, K. Yu.; Prakash, G. K. S.; Rasul, G.; Olah, G. A. Heterocycles 2004, 62, 757–772.
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8. (a) Olah, G. A.; Prakash, G. K. S.; Molnar, A.; Sommer, J. Superacid Chemistry, 2nd ed.; Wiley: New York, 2009; (b) Smith, G. P.; Dworkin, A. S.; Pagni, R. M.; Zingg, S. P. J. Am. Chem. Soc. 1989, 111, 525–530; (c) Smith, G. P.; Dworkin, A. S.; Pagni, R. M.; Zingg, S. P. J. Am. Chem. Soc. 1989, 111, 5075–5077. 9. Nenitzescu, C. D.; Cantuniari, R. Chem. Ber. 1933, 66, 1097–1100. 10. Koltunov, K. Yu.; Repinskaya, I. B.; Borodkin, G. I. Russ. J. Org. Chem. 2001, 37, 1534–1541. 11. Bakoss, H. J.; Roberts, R. M. G.; Sadri, A. R. J. Org. Chem. 1982, 47, 4053–4055. and references cited therein. 12. (a) Olah, G. A.; Meyer, M. W.; Overchuk, N. A. J. Org. Chem. 1964, 29, 2313– 2315; (b) Roberts, R. M.; Roengsumran, S. J. Org. Chem. 1981, 46, 3689–3695; (c) Al-Dosari, M. A. Arabian J. Sci. Eng. 2010, 35, 7–17. and references cited therein. 13. Golounin, A. V.; Sokolenko, V. A.; Shakirov, M. M. Russ. Chem. Bull. 1997, 46, 1110–1112. 14. Korda, A.; Tyrlik, S. J. Mol. Catal. 1986, 37, 339–347. 15. (a) Huang, C.; Ghavtadze, N.; Chattopadhyay, B.; Gevorgyan, V. J. Am. Chem. Soc. 2011, 133, 17630–17633; (b) Ozaki, Y.; Oshio, I.; Ohsuga, Y.; Kaburagi, S.; Sung, Z.-Z.; Kim, S.-W. Chem. Pharm. Bull. 1991, 39, 1132–1136; (c) Sinclair, I. W.; Proctor, G. R. J. Chem. Soc., Perkin Trans. 1 1975, 2485–2488; (d) Iverson, S. L.; Shen, L.; Anlar, N.; Bolton, J. L. Chem. Res. Toxicol. 1996, 9, 492–499; (e) Hecker, E.; Nowoczek, G. Z. Naturforsch. B: Anorg. Chem., Org. Chem., Biochem., Biophys. 1966, 21, 153–160.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Reactions of 2,3-naphthalenediol with cyclohexane in the presence of aluminum halides Zhongwei Zhu a,b, Ludmila A. Ostashevskaya a, Konstantin Yu. Koltunov a,c,⇑ a
Novosibirsk State University, Pirogova, 2, Novosibirsk 630090, Russia Heilongjiang University, Xue Fu Road, No. 74, Nan-gang, Harbin 150080, PR China c Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, Pr. Akademika Lavrentieva, 5, Novosibirsk 630090, Russia b
a r t i c l e
i n f o
Article history: Received 28 January 2015 Revised 10 March 2015 Accepted 13 March 2015 Available online 19 March 2015 Keywords: Naphthols Superacids Superelectrophiles Ionic hydrogenation
a b s t r a c t 2,3-Naphthalenediol (7) undergoes selective ionic hydrogenation with cyclohexane in the presence of excess AlCl3 or AlBr3 to afford 5,6,7,8-tetrahydro-2,3-naphthalenediol (8). Compound 8 can be further converted into 5,6,7,8-tetrahydro-1,2-naphthalenediol (9) and pyrocatechol (10). The discovered reactions represent new and efficient synthetic approaches to produce difficult to obtain derivatives of 7. The mechanistic aspects of the reactions, and the potential involvement of superelectrophilic dicationic intermediates, are discussed. Ó 2015 Elsevier Ltd. All rights reserved.
Introduction It is known that 1- and 2-naphthols react with benzene and other arenes under the influence of an excess of aluminum halides, HUSY-zeolites or in the HF–SbF5 superacid medium to give 4-aryl-1- and 4-aryl-2-tetralones (structures 1 and 2, respectively, Scheme 1).1 In addition, naphthols undergo selective ionic reduction by alkanes under similar reaction conditions to offer 1- and 2-tetralones (structures 3 and 4, Scheme 1).2 The mechanism of these reactions was recognized to involve superelectrophilic3 dications 5 and 6 as the key intermediates formed by C,C-diprotonation. A number of such dications have indeed been generated as long-lived species by dissolving naphthols and their derivatives in liquid superacids.4 Furthermore, some isomeric naphthalenediols have been shown to react with benzene, o-dichlorobenzene and cyclohexane by analogy with the parent naphthols to afford the corresponding hydroxy tetralones (Scheme 2).1c,e,5 On the other hand, 1,4-naphthalenediol has proved to be totally inert toward benzene and cyclohexane under the same reaction conditions.1b,2a In a continuation of our interest in the superelectrophilic activation of naphthols1,2,4,5 and their heterocyclic analogues,6 a study on the reactivity of 2,3-naphthalenediol (7) with cyclohexane is reported herein with the aim of discovering new synthetic
⇑ Corresponding author. Tel.: +7 383 326 9765; fax: +7 383 330 8056. E-mail address: [email protected] (K.Yu. Koltunov). http://dx.doi.org/10.1016/j.tetlet.2015.03.059 0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
OH
O
O
ArH (AlkH) strong acid
3
1 Ar OH ArH (AlkH)
O
O
strong acid
4
2 Ar + O X
+ O X
key intermediates: +
5
+
6
_ _ X = H or AlnCl3n or Aln Br3n
Scheme 1. Reactions of naphthols with arenes (ArH) and alkanes (AlkH).
approaches to naphthol derivatives. The latter are generally considered as important intermediates for medicinal chemistry and other practical applications.1e,5b The main aim of the work was also to determine the regioselectivity of any potential reactions. Results and discussion Diol 7 was found to react smoothly with cyclohexane in the presence of a 5-fold molar excess of AlBr3 or AlCl3 to give a mixture of products including 5,6,7,8-tetrahydro-2,3-naphthalenediol (8),
2255
Z. Zhu et al. / Tetrahedron Letters 56 (2015) 2254–2257 OH HO
HO
OH
OH
+ HO
HO
AlBr3 or AlCl3 1,5-, 1,6- and 1,7-diols OH
O
O
ArH (cyclo-C6H12)
11
Ar
OH
O HO
O HO
OH
X O
+
H
H
+
13
AlBr3 or AlCl3 2,6- and 2,7-diols
12
X O
ArH (cyclo-C6H12)
+
OH
14
OH
+ +
OH
15
OH
_ _ X = H or AlnCl3n or AlnBr3n
Ar
Scheme 2. Reactions of naphthalenediols with arenes (ArH) and cyclohexane. Scheme 4. Reaction intermediates proposed.
5,6,7,8-tetrahydro-1,2-naphthalenediol (9), and pyrocatechol (10) (Scheme 3, Table 1). The selectivity of this reaction is strongly dependent on the reaction conditions. Thus, 7 reacts slowly with cyclohexane in an AlBr3–CH2Br2 acid system at room temperature to offer 8 as the major product (Table 1, entry 1). The same reaction proceeds more readily in the presence of AlCl3 at elevated temperature (110 °C, pressure tube) in the absence of solvent to afford 8 in 90% yield after only 10 min (Table 1, entry 2). The latter procedure can be considered as an efficient and convenient synthetic approach for the selective partial hydrogenation of 7 to 8. Upon increasing the reaction time, conversion of 7 into 9 was observed to occur after 15–60 min using the same conditions (Table 1, entries 3–5). Further increases of the reaction time resulted in an increase in the amount of 10 (Table 1, entries 6–8). Therefore, products 9 and 10 are derived from 8 as a result of further transformations. It is evident that the reduction of 7 to 8 proceeds via a quite different reaction mechanism compared to that of 1- and 2-naphthols, which react with alkanes and arenes at their phenolic ring (Scheme 1). Conversely, electrophilic activation of 7 is achieved through the protonation of its benzene ring. In principle, both the C5(8)- and C6(7)-atoms of 7 can be protonated to form ions 11 and 12, respectively (Scheme 4). However, monocationic species such as 11 and 12 may not be electrophilic enough to react with cyclohexane.6a Most likely, dicationic species 13–14 are the true reactive intermediates (Scheme 4). The analogous O,Cdiprotonation has been demonstrated earlier for 2-naphthol when dissolved in the HF–SbF5–SO2ClF superacid system at
OH OH
7
OH
OH
cyclo-C6H12
+
acid 8
OH
OH OH +
9
OH
10
Scheme 3. Reaction of 7 with cyclohexane in the presence of aluminum halides (for reagents and conditions see Table 1).
Table 1 Reactions of 7 with cyclohexane (30 equiv)
a
Entry
Acid, conditions
Molar ratio 8:9:10a
1 2 3 4 5 6 7 8 9 10
AlBr3 (5 equiv) CH2Br2, 25 °C, 24 h AlCl3 (5 equiv), 110 °C, 10 min AlCl3 (5 equiv), 110 °C, 15 min AlCl3 (5 equiv), 110 °C, 30 min AlCl3 (5 equiv), 110 °C, 1 h AlCl3 (5 equiv), 110 °C, 3 h AlCl3 (5 equiv), 110 °C, 5 h AlCl3 (5 equiv), 110 °C, 10 h AlCl3 (3 equiv), 110 °C, 1 h AlCl3 (1.5 equiv), 110 °C, 1 h
90:7:3 90:5:5 21:64:15 21:61:18 20:56:24 33:34:33 44:13:43 27:9:64 90:8:2b 90:8:2c
Complete conversion of 7 was achieved. The ratio given is based on 1H NMR spectroscopic data. b Conversion of 7 is approximately 30%. c Conversion of 7 is <5%.
80 °C, which is in contrast to the formation of 6 (X = H) in the same acid at 40 °C.4b Notably, such an activation of the benzene rather than phenolic moiety is more typical for N-heterocyclic derivatives of 2-naphthol and their reactions with benzene and cyclohexane.7 Generation of C,C-diprotonated species 15 could be an additional way of (super)electrophilic activation of 7 (Scheme 4). It should be noted that intermediates 13 and 14 may be additionally O-protonated/coordinated at the intact hydroxyl group. This will increase the electrophilicity of these species even further. A catalytic amount of protic superacid (HHal–AlnHal3n or H2O–AlnHal3n), which is required for the generation of 13–15, is normally present in such reaction media due to the presence of traces of water in the starting materials. The acid strength of HHal–AlnHal3n (Hal = Br, Cl) is estimated to be 15 to 18 on the HO scale.8 Scheme 5 represents a probable reaction mechanism for the conversion of 7 into 8 involving the likely intermediacy of 13. According to Scheme 5, intermediate 13 undergoes selective hydrogenation with cyclohexane to give intermediate 16, which undergoes additional protonation followed by reaction with a second molecule of cyclohexane. Under the reaction conditions cyclohexane exists in equilibrium with methylcyclopentane.9 Both cyclohexane and methylcyclopentane can convert into isomeric cations C6H+11, which in turn react with an excess of cyclohexane/methylcyclopentane to give isomeric C6H11–C6H11 alkanes (C6H11 = cyclohexyl, methylcyclopentyl; NMR and GC–MS data). These hydrocarbons are considered as the final oxidation product in such reactions.10 The conversion of 8 into 9 most probably proceeds through an electrophilic transalkylation mechanism (Scheme 6). The key intermediate in this case could be O,C-diprotonated/coordinated species 17. Since the loss of a primary carbocation from an arenium ion has not yet been properly ascertained,11 the formation of intermediate 18 seems highly unlikely, and rearrangement occurring through the spirocyclic intermediate 19 can thus be suggested (Scheme 6). Indeed, the acid-catalyzed intramolecular isomerization of xylenes and diethylbenzenes occurs predominantly via 1,2-bond migrations.12 It is remarkable that primary carbocations 18 (if they were generated) do not rearrange into more stable derivative 20 before cyclization to give the expected products 21 and 22 (Scheme 7). Presumably, the phenol moiety in 20 is deactivated by O-coordination with AlHal3 and does not react with the adjacent secondary carbocation center. On the other hand, the absence of compounds
13
+ X O H
cyclo -C6H12 -C6H11+
16
H+, cyclo-C6H12 -C6 H11+
8
-X+ _ _ X = H or AlnCl3n or AlnBr3n
OH
Scheme 5. Proposed mechanism for the reduction of 7 to 8.
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Z. Zhu et al. / Tetrahedron Letters 56 (2015) 2254–2257
8
+ H O X + OH
X+, H+
17
superelectrophilic intermediates. This is in contrast to the regioselectivity shown in similar reactions for the parent 2-naphthol and isomeric 2,6- and 2,7-naphthalendiols.1,2,5 From a practical viewpoint, diol 7 is efficiently modified into difficult to obtain15 derivatives 8 and 9 using simple procedures and readily available reagents.
+ H O X +
OH
1,2-shift + X O H
+
OH
18
19
+ X O H + OH
OH
Experimental 5,6,7,8-Tetrahydro-2,3-naphthalenediol (8)
+ H O X +
OH
1,2-shift + H O X + OH
-X+, -H+
9
+ H O X
+
-X+, -H+
_ _ X = H or AlnCl3n or AlnBr3n
Scheme 6. Proposed mechanisms for the conversion of 8 into 9.
18
~ H+
OH
+ X O H
+
20 _ X = H or Aln Cl3n
OH _ or AlnBr3n
OH
OH +
21
OH
22
not observed
Scheme 7. A possible, but not observed reactivity of 18.
21 and 22 among the reaction products is in line with the proposed limited contribution of 18 in the conversion of 8 to 9. Finally, the formation of 10 can be explained by complete dealkylation of 8 and 9 under the highly acidic conditions. Generation of partially dealkylated intermediates 18 and 20 can be considered as an initial step in such a reaction pathway, while the absence of 21 and 22 in the reaction mixtures may be related to their rapid dealkylation to 10. The latter possibility is in agreement with relatively smooth dealkylation of 4-cyclohexylpyrocatehol in the presence of excess AlBr3.13 Alternatively, more sophisticated reaction mechanisms, such as those suggested earlier for intermolecular transalkylation–dealkylation in ethylbenzene (with the exception of the intermediacy of a primary carbocation),11,12b can explain the formation of catechol 10. It is worth noting that tetralin (a close analogue of 8 and 9) also undergoes dealkylation in the presence of AlCl3 at 110 °C.14 However, this reaction is rather unselective and gives benzene along with a large variety of alkylated products. It should be also noted that a 5-fold molar excess of aluminum halides is not essential and a decrease in the loading is possible (Table 1, entries 9 and 10). This, however, slows down the reaction. Moreover, the use of less than a 1.5-fold molar excess of AlCl3 or AlBr3 completely suppresses the reaction. Clearly, the excess of aluminum halide provides an acid strength sufficient to form dicationic intermediates such as 13–15 and 17. Conclusions The model reactions shown with cyclohexane demonstrate the activity and regioselectivity patterns of the current synthetic approach (superelectrophilic activation with an excess of aluminum halides) toward diol 7. It has been shown that the reagents react exclusively with the benzene ring in 7, which is most plausibly interpreted in terms of key O,C-diprotonated/coordinated
A mixture of 7 (1.0 g, 6.25 mmol), AlCl3 (4.2 g, 31.5 mmol), and cyclohexane (20 mL) was stirred in a 100 mL Ace pressure tube at 110 °C (oil bath temperature) for 10 min, followed by cooling and pouring the mixture onto several grams of ice. The resulting mixture was extracted with Et2O. The organic phase was washed with water, dried over anhydrous MgSO4, and concentrated in vacuo to give a mixture of 8, 9, and 10 and isomeric C12H22-alkanes in 18:1:1:40 molar ratio (1H NMR and GC–MS data). The mixture was separated by flash column chromatography with benzene– acetone (5:1) to give diol 8 (0.78 g, 76%). Mp 126–129 °C, lit.15b Mp 127–130 °C. 1H NMR (500 MHz, CDCl3) d 1.72–1.79 (m, 4H), 2.61–2.69 (m, 4H), 5.02 (br s 2H), 6.58 (s, 2H). 13C NMR (125 MHz, CDCl3) d 23.4, 28.9, 115.8, 129.8, 141.4. GC–MS [M]+: 164. 5,6,7,8-Tetrahydro-1,2-naphthalenediol (9) A mixture of 7 (0.2 g, 1.25 mmol), AlCl3 (0.83 g, 6.2 mmol), and cyclohexane (5 mL) was stirred in a 15 mL Ace pressure tube at 110 °C for 15 min to provide, after usual workup, the crude product (mixture of 8, 9, 10 in 21:64:15 molar ratio and C12H22-alkanes), which was separated by flash column chromatography with benzene–acetone (5:1) to give compound 9 (0.12 g, 58%). 1H NMR (500 MHz, CDCl3) d 1.72–1.78 (m, 2H), 1.78–1.84 (m, 2H), 2.66 (t, J 6.5 Hz, 2H), 2.69 (t, J 6.5 Hz, 2H), 5.17 (br s 2H), 6.55 (d, J 8 Hz, 1H), 6.66 (d, J 8 Hz, 1H). 13C NMR (125 MHz, CDCl3) d 22.7, 23.10, 23.13, 29.2, 112.7, 120.8, 124.2, 130.7, 140.6, 141.6. GC–MS [M]+: 164. Pirocatechol (10) A mixture of 7 (0.2 g, 1.25 mmol), AlCl3 (0.83 g, 6.2 mmol), and cyclohexane (5 mL) was stirred in a 15 mL Ace pressure tube at 110 °C for 10 h to afford, after usual workup and chromatographic purification, compound 10 (0.063 g, 46%). 1H NMR (500 MHz, CDCl3) d 5.05 (br s 2H), 6.78–6.88 (m, 4H). 13C NMR (125 MHz, CDCl3) d 115.7, 121.4, 143.7. GC–MS [M]+: 110. Acknowledgments We thank the reviewers for their helpful and constructive comments. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.03. 059. References and notes 1. (a) Methoden der Organischen Chemie; Thomas, H. G., Ed.; Thieme: Stuttgart, 1976; Vol. 7, p 1710. 2b; (b) Repinskaya, I. B.; Koltunov, K. Yu.; Shakirov, M. M.; Shchegoleva, L. N.; Koptyug, V. A. Russ. J. Org. Chem. 1993, 29, 803–810; (c) Koltunov, K. Yu.; Repinskaya, I. B.; Shakirov, M. M.; Shchegoleva, L. N. Russ. J.
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