Zinc-mediated reductive dimerizations of telluroxanthone and selenoxanthone. Tellurium-selenium selectivity

Article abstract of DOI:10.1016/S0040-4039(00)00997-7

Reductive dimerizations of 9H-selenoxanthen-9-one (3) and 9H-telluroxanthen-9-one (4) (1:1) with zinc in boiling AcOH and HCl for 1 hour gave the bistricyclic ethanes 9,9'-bi(9H-selenoxanthene (10), 9,9'-bi(9H-telluroxanthene) (11) and 9-(9'H-telluroxanthen-9'-yl)-9H-selenoxanthene (12) in the ratios 21 (10):35 (11):44 (12) (in addition to 9H-selenoxanthene (13) and 9H-telluroxanthene (14)) Analogous reactions of 4 and 9H-thioxanthen-9-one (9) (1:1) and 3 and 9 (1:1) gave the corresponding bistricyclic ethanes. The reactions were chalcogen selective with a preference towards the tellurium-bridged bistricyclic ethanes. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00997-7

Tetrahedron Letters 41 (2000) 6157±6160
Zinc-mediated reductive dimerizations of telluroxanthone and
selenoxanthone. Tellurium±selenium selectivity
Amalia Levy and Israel Agranat*
Department of Organic Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
Received 2 May 2000; accepted 14 June 2000
Abstract
Reductive dimerizations of 9H-selenoxanthen-9-one (3) and 9H-telluroxanthen-9-one (4) (1:1) with zinc
in boiling AcOH and HCl for 1 hour gave the bistricyclic ethanes 9,90-bi(9H-selenoxanthene (10), 9,90-
bi(9H-telluroxanthene) (11) and 9-(90H-telluroxanthen-90-yl)-9H-selenoxanthene (12) in the ratios 21
(10):35 (11):44 (12) (in addition to 9H-selenoxanthene (13) and 9H-telluroxanthene (14)). Analogous
reactions of 4 and 9H-thioxanthen-9-one (9) (1:1) and 3 and 9 (1:1) gave the corresponding bistricyclic
ethanes. The reactions were chalcogen selective with a preference towards the tellurium-bridged bistricyclic
ethanes. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: bistricyclic ethanes; overcrowding; 125Te and 77Se NMR; reductive couplings; chalcogen±heterocyclics.
Tricyclic aromatic ketones (TAKs) (1), have served as starting materials for the syntheses of a
variety of tricyclic drugs, e.g. the antidepressant amitriptyline, the non-sedative antihistaminic
loratadine and desloratadine, the antiallergic, appetite stimulant cyproheptadine and the anti-
psoriatic anthralin.1 3 TAKs have also served as synthons leading to overcrowded bistricyclic
enes (2),4 e.g. the thermochromic and photochromic bianthrone (1, X,Y: CˆO). While the reac-
tions of many (6,6,6) and (6,7,6) TAKs (1) have been extensively studied, the scope of the
chemistry of 9H-selenoxanthen-9-one (3) and 9H-telluroxanthen-9-one (4) is relatively limited.5 7
The oldest and one of the simple methods of syntheses of 2 is the reductive dimerization of a
TAK, employing zinc in acetic acid and hydrochloric acid, e.g. the century old synthesis of 9,90-
bi(xanthen-9-ylidene) (2, X,Y: O)8 from 9H-xanthen-9-one (1, X: O). It seemed reasonable9 and
promising to apply this method to the syntheses of the selenium- and tellurium-bridged homo-
merous bistricyclic enes 9,90-bi(selenoxanthen-9-ylidene) (5) and 9,90-bi(telluroxanthen-9-ylidene)
(6) and the heteromerous bistricyclic ene 9-(9H-telluroxanthen-90-ylidene)-9H-selenoxanthene (7) by
reductive dimerizations of 3,4 and a mixture of 3 and 4, respectively.0Bistricyclic enes 5 and 6 have
recently been synthesized by other methods.10 The preparation of 9,9 -bi(thioxanthen-9-ylidene) (8)
* Corresponding author. Tel: 972-2-6585221; fax: 972-2-6511907; e-mail: isria@vms.huji.ac.il
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00997-7

6158
by zinc-mediated reductive coupling of 9H-thioxanthen-9-one (9) has been documented.11 We
report the zinc-mediated reductive dimerizations of 3 and 4 and of mixtures of 3 and 4, 3 and 9,
and 4 and 9, with special emphasis on tellurium versus selenium selectivity.
The reductive couplings of 312 and 45,13 were carried out with zinc powder in boiling acetic acid
in the presence of concentrated hydrochloric acid (100:1.25). The composition of the products of
the reactions were determined by 1H, 13C, 77Se and 125Te NMR spectroscopies. Assignments were
made through two-dimensional correlation spectroscopy (COSY, HSQC, HMBC). A 1:1 mixture
of 3 and 4 with Zn/AcOH/HCl gave 9,90-bi(9H-selenoxanthene) (10), 9,90-bi(9H-telluroxanthene)
(11), 9-(90H-telluroxanthen-90-yl)-9H-selenoxanthene (12), 9H-selenoxanthene (13) and 9H-tell-
uroxanthene (14) in the ratios of 14:24:30:17:15, respectively. None of the bistricyclic enes 5±7
were obtained. When the reaction was carried out for 3 hours, the ratios of the products were 15
(10):20 (11):26 (12):30 (13):9 (14). Table 1 gives the 1H, 13C, 77Se, and 125Te NMR chemical shifts
0
of 10±12 and related bistricyclic ethanes due to H9, H9 , C9, C9 , Se10, Se10 , Te10 and Te10 . The
0
0
0
0
NMR assignments in 12 were based on the lead chemical shift of C4a and C10a of the tell-
0
uroxanthene moiety at 114.20 ppm, which is characteristic for C (aromatic)-Te. For comparison,
10
0
0
in 11, dC4a =114.29 ppm. The aliphatic protons H9 and H9 of 12 appear as an AB quartet at d
4.938 ppm and d 5.168 ppm, respectively (J=11.1 Hz), dH9±dH90=^0.230 ppm. Noteworthy, in
the C NMR spectrum of 12 is dC9±dC9 =+5.43 ppm. For comparison, d(C9) (10)±d(C9)
13
0
(11)=2.39 ppm.10 The molecular structures of 10 and 11 indicated that these homomerous
bistricyclic ethanes di€er in folding dihedral angles, 49.2ꢀ (10) versus 41.2/39.5ꢀ(11), and in
r(C9±C90), 150.1 pm (10) versus 157.4 pm (11).10 The above di€erence between dC9 and dC90 in 12
may re¯ect di€erent folding dihedral angles in the selenoxanthene and telluroxanthene moieties.15
These chemical shifts are probably a€ected by Te and Se in the respective confronting
telluroxanthene and selenoxanthene moieties. Another interesting feature in the NMR spectra of
0
0
12 is the Ád values of H9 versus H9 and of C9 versus C9 , between the heteromerous 12 and the
0
homomerous 10 and 11. Thus, Ád(H9)=+0.337ppm, while Ád(H9 )=^0.338 ppm; Ád(C9)=^1.48
0
ppm, while Ád(C9 )=+1.56 ppm. The reductive homo-dimerization of 3 with zinc in AcOH/HCl
gave after 3 hours 5, 10 and 13 in the ratios of 25:37.5:37.5, with only traces of 3. After 1 hour, 5
was absent and the ratios were 32 (10):46 (13):22 (3). An analogous reductive homo-dimerization
of 4 gave after 3 hours 11 and 14 in the ratio of 96:4. After 1 hour, 11 was isolated in 67% yield
and the 11:14:4 ratio was: 84:11:5, while no 6 was evident. In addition to 11 and 14, a third
product (d125Te=676.43 ppm, d1H=4.758 ppm (bs)) was formed which was not identi®ed. The
reductive dimerization of 9H-thioxanthen-9-one (9) gave a mixture of 8 and 9,90-bi(9H-
thioxanthene) (15)16 in the ratios of 89:11 (1 hour), 77:23 (3 hours), respectively. The synthesis of
11 by a reductive dimerization of 4 with zinc in AcOH/HCl was ®rst reported by Sadekov and

6159
Minkin, et al.9 We have recently reported the syntheses of 10 and 11 by low valent titanium-
induced reductive homo-dimerizations of 3 and 4, respectively, using TiCl4/Zn/pyridine.10
Table 1
1
Selected H, 13C, 77Se and 125Te chemical shifts (in ppm) of bistricyclic ethanes 10±12 and 15±17
The most interesting result of the present study is the distribution of the bistricyclic ethanes
formed in reductive dimerizations of 3 and 4: 21 (10):35 (11):44 (12) (1 hour) and 24 (10):34
(11):43 (12) (3 hours), as compared with the statistical distribution 25 (10):25 (11):50 (12). Thus,
the reaction was chalcogen selective: Te/Te-bridged 11 was preferred over Se/Te-bridged 12 and
over Se/Se-bridged 10, while 12 was preferred over 10. More pronounced chalcogen selectivities
were observed in the analogous reductive dimerizations of 9. The reaction (1 hour) of 4 and 9
(1:1) gave 15, 11, and S/Te-bridged 16 in the ratios 10:34:55, while the reaction (1 hour) of 3 and 9
gave 15, 10 and the S/Se-bridged 17 in the ratio 20:24:51. The ®rst step in the reductive
dimerizations of 3 and 4 is probably the formation of the radical anions of 3 and 4. The above
preferences stem from the enhanced reactivity of 4^Á as compared with 3^Á. The Te homo-
dimerization [4^Á+4^Á] was preferred over the Te/Se hetero-dimerization [4^Á+3^Á] and over the Se
homo-dimerization [3^Á+3^Á], giving the respective Te/Te, Te/Se, and Se/Se pinacols. The
bistricyclic ethanes were probably formed by hydrogenolysis of the pinacols. The zinc-mediated
reductive dimerizations of 3 and 4 showed a higher degree of tellurium versus selenium selectivity
than the respective low valent titanium-mediated reactions. The low valent titanium induced
reductive dimerizations of a 1:1 mixture of 3 and 4 gave the bistricyclic ethanes 10, 11, and 12 in
the ratio 19:31:50, respectively, while none of the bistricyclic enes 5, 6 and 7 and the 9H-
chalcogenoxanthenes 13 and 14 were obtained. In conclusion, the reductive dimerizations of
chalcogenoxanthen-9-ones (1, X: O,S,Se,Te) favor the formation of the bistricyclic ethenes in the
order O>S>Se>Te and the formation of the bistricyclic ethanes in the order Te>Se>S>O.
References
1. Kleemann, A.; Engel, J.; Kutschrer, B.; Reichert, D. in Pharmaceutical Substances: Syntheses, Patents,
Applications, 3rd ed.; Georg Thieme: Verlag, Stuttgart, 1999.

6160
2. Dollery, C., Ed. Therapeutic Drugs, 2nd ed.; Churchill Livingston: Edinburgh, 1999.
3. Graul, A.; Leeson, P. A.; Castaner, J. Drugs of the Future 2000, 25, 339±346.
4. Biedermann, P. U.; Stezowski, J. J.; Agranat, I. In Advances in Theoretically Interesting Molecules; Thummel, R. P.
Ed.; JAI Press: Stamford, CN, 1998; Vol. 4, pp. 245±322.
5. Sadekov, I. D.; Minkin, V. I. Adv. Heterocycl. Chem. 1995, 63, 1±60.
6. Irgolic, K. J. In Methods of Organic Chemistry (Houben-Weyl), Vol. E12b; Klamann, D., Ed. Organotellurium
compounds. Georg Thieme: Verlag, Stuttgart, 1990, pp. 830±840.
7. Karle, I. L.; Karle, J. In Organic Selenium Compounds: Their Chemistry and Biology; Klayman, L. D.; Gunther,
W. H. H., Eds.; Interscience: London, 1973, pp. 989±1015.
8. Gurgenjanz, G.; v. Konstanecki, St. Ber. Dtsch. Chem. Ges. 1895, 28, 2310±2311.
9. Karaev, K. Sh.; Furmanova, N. G.; Belov, N. V.; Sadekov, I. D.; Ladatko, A. A.; Minkin, V. I. Zh. Strukt. Khim.
1981, 22, 106±111.
10. Levy, A.; Biedermann, P. U.; Cohen, S.; Agranat. I. J. Chem. Soc., Perkin Trans. 2 2000, 725±735.
11. Mayer, F. Ber. Dtsch. Chem. Ges. 1909, 42, 1132±1137.
12. Sindelar, K.; Svatek, E.; Metysova, J.; Metys, J.; Protiva, M. Collection Czech. Chem. Commun. 1969, 34, 3792±
3800.
13. Sadekov, I. D.; Ladatko, A. A.; Minkin, V. I. Khim. Geterotsikl. Soedin. 1980, 1342±1349.
14. Nakanishi, W.; Yamamoto, Y.; Hayashi, S.; Tukada, H.; Iwamura, H. J. Phys Org. Chem. 1990, 3, 369±374.
15. Levy, A.; Biedermann, P. U.; Cohen, S.; Agranat, I. Phosphorus, Sulfur, and Silicon and Related Elements 1998,
136/138, 139±142.
16. Schonberg, A.; Mustafa, A. J. Chem. Soc. 1945, 657±660.