Thallium(III) Acetate


[2570-63-0]  · C6H9O6Tl  · Thallium(III) Acetate  · (MW 381.53)

(oxidation of alkenes4 and alkynes;5 oxidation of conjugated dienes;7 hydroxylation of double bonds;11 cleavage of cyclopropane rings;15 oxidation of enamines;18 oxidative rearrangements;20,21,23 bromination of aromatic compounds;24 oxidation of thiols25 and p-toluenesulfonylhydrazones;26 formation of acyloxy carboxylic acids;27 oxidative cyclizations28)

Physical Data: mp 195 °C.

Solubility: sol hot acetic acid, alcohols, H2O.

Form Supplied in: white solid; commercially available (98.6%). Drying: dry over P2O5.

Preparative Methods: was first described by Meyer and Goldschmidt1 in 1903. It can also be prepared2 by dissolving thallium(III) oxide in acetic acid and acetic anhydride and stirring at 80-90 °C. The solution is filtered, cooled and the product obtained is recrystallized.

Purification: use after crystallization from acetic acid for best results.

Handling, Storage, and Precautions: remains stable for long periods if kept in a well-sealed desiccator and away from light. It is extremely poisonous. Use in a fume hood.

Oxidation of Alkenes and Alkynes.

It was expressed by Kabbe3 that thallium(III) acetate as an oxidizing agent occupies an important place between Lead(IV) Acetate and Mercury(II) Acetate. Oxidation4 of cyclohexene (1) with thallium(III) acetate in acetic acid at rt (several days) yields cis/trans diacetates (2) and (3) (40-50%), ring contracted diacetate (4) and aldehyde (5) (50-60%), and allylic oxidation product (6) (2-3%) (eq 1). In dry solvent the trans-diacetate (2) is obtained in major yield (88%), whereas in moist solvent the cis-diacetate (3) (81%) predominates. It has been observed that similar oxidation with lead(IV) acetate yields the same five products but the yield of allylic acetate (6) is increased by 37% whereas the oxidation carried out with mercury(II) acetate affords exclusively the allylic acetate (6). It has been observed5 that terminal alkynes (7) react with thallium(III) acetate in acetic acid or chloroform at 0-20 °C to give a new type of oxythallation adduct (8), which on being heated with one equivalent of thallium(III) acetate can be converted to methyl ketone (9) (eq 2). Although this procedure for the preparation of ketones was reported6 previously, the intermediates were not isolated at that time.

Oxidation of Conjugated Dienes.

Conjugated dienes (isoprene, 1,3-butadiene, 2,3-dimethyl-1,3-butadiene, etc.) react with thallium(III) acetate in acetic acid at 10-65 °C (0.5-15 h) to give an isomeric mixture (1,2 and 1,4) of the corresponding diacetoxyalkenes in 10-72% yield.7 All the dienes studied except 1,3-cyclopentadiene afford the 1,2-addition adduct predominantly. The reaction of 2,3-dimethyl-1,3-butadiene (10) with thallium(III) acetate has been reported to give the 1,2-addition product (11) in good yield and the 1,4-addition product (12) in inferior yield (eq 3). In the oxymercuration of dienes with mercury(II) acetate the formation of 1,4-addition products has not been reported.8 The reaction of diene (13) with thallium(III) acetate has been described (eq 4).9 The resulting product on alkaline hydrolysis has been found to yield alcohols (14), (15), (16), (17), and (18). The alcohols (15) and (16) have been utilized for the synthesis of drimane sesquiterpenes. It is worthwhile to mention that the conjugated dienes also undergo cis addition10 with Thallium(III) Trifluoroacetate.

Hydroxylation of Double Bonds.

The stereoselective cis hydroxylation of unsaturated steroids such as (19) has been effected11 with thallium(III) acetate in acetic acid. In addition to the cis-glycol monoacetates (20) and (21) (76%), small amounts of cis-diacetate (22) (7%) and trans-glycol monoacetates are obtained (eq 5). The alkaline hydrolysis of monoacetates (20) and (21) affords the triol (23). A number of steroidal alkenes have been hydroxylated with this reagent. This constitutes a convenient procedure for the cis hydroxylation of double bonds which have been effected with other procedures.12-14

Cleavage of Cyclopropanes.

The phenylcyclopropane (24) undergoes cleavage15 with thallium(III) acetate in acetic acid, yielding mainly diacetoxypropane (25) (92%) and a small amount of trans-cinnamyl acetate (26) (8%) (eq 6). The reaction can also be effected with thallium(III) oxide because under the reaction conditions it is converted to thallium(III) acetate and thus the use of the moisture sensitive thallium(III) acetate can be avoided. The same cleavage reaction when effected with lead(IV) acetate16 yields the same products (25) (63%) and (26) (5%) along with another diacetate (27) (32%).

The formation of the products (25) and (26) can be accounted for as a result of the cleavage of C-1-C-2, whereas the cleavage of bond C-2-C-3 yields the diacetate (27). It is important to note that the cleavage of cyclopropane with thallium(III) acetate, which requires 120 h at 75 °C for completion, can be effected with lead(IV) acetate in 10 h.

The cyclopropane ring of methyl ent-trachyloban-19-oate (28) undergoes an interesting cleavage17 with thallium(III) acetate in acetic acid, affording four products (29), (30), (31), and (32) (eq 7).

Oxidation of Enamines.

The oxidation of various enamines with thallium(III) acetate at rt in glacial acetic acid or chloroform followed by hydrolysis gives a-acetoxy derivatives of the parent ketone.18 Thus morpholinocyclohexene (33) was converted to 2-acetoxycyclohexanone (34) in 70% yield (eq 8). The same reaction can also be carried out on a combination of cyclohexene and morpholine (in situ generation of enamine) and this gives a superior yield (77%). The yield was lower when the pyrrolidine enamine, instead of morpholine enamine, was used. The yield of a-acetoxy ketone is superior to that obtained by direct oxidation of ketones with thallium(III) acetate or lead(IV) acetate. This particular reaction is of preparative value. It has received application in the synthesis of antitumor alkaloids of the vinblastine group.19 It is necessary to point out that the synthetic utility of this oxidation reaction depends on the use of the equivalent amount of the reaction components.

Oxidation of Ketones.

A number of cyclic ketones, specially steroidal ketones, have been subjected to oxidation by thallium(III) acetate in acetic acid. Three types of reactions have been noted during the oxythallation of ketones,20 namely acetoxylation, dehydrogenation, and ring contraction. The ketone (35) on treatment with thallium(III) acetate in acetic acid yields the dienone (36) and acetoxy derivative (37) in 23% and 30% yields, respectively (eq 9). Both products presumably arise from the same thallium adduct (A). The ketone (38) on similar treatment affords the ketone (39) and the ring contracted acid (40) (eq 10). The ketone (39) probably arises from a thallium enolate (B).

The oxidation of a,b-unsaturated ketones (41), (42), and (43) with thallium(III) acetate in acetic acid yields only the dienones (44), (45), and (46), respectively (eqs 11-13).21 The formation of other products, as in the case of steroidal ketones, is not observed. The oxidation of these ketones with 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gives better yields of the dienone, whereas little improvement in the yield of the dienones is observed when the oxidation reaction is repeated with benzeneseleninic anhydride (BSA) (see Benzeneseleninic Acid). These experiments indicate that the potential of thallium(III) acetate is similar to that of DDQ or BSA.

Oxidative Rearrangements.

Molecular rearrangement has also been observed during oxidation reactions with thallium(III) acetate in acetic acid or methanol. The 3b-acetoxypregn-5-en-20-one (47) undergoes Wagner-Meerwein rearrangement with thallium(III) acetate in acetic acid yielding the product (48)20 as a result of attack on the more stable D17,20-enol (eq 14). This is in contrast to the kinetically controlled acetoxylation at C-21 in reaction with lead(IV) acetate.22 The chalcone (49) on treatment with thallium(III) acetate in boiling methanol yields the isoflavone (50) (eq 15).23 This finding proves that thallic acid induced rearrangement involves exclusively 1,2-aryl migration and thus demonstrates the direct utilization of chalcones rather than flavanones in isoflavone biosynthesis.

A very interesting rearrangement of the ketone (51) was observed with thallium(III) acetate in acetic acid.21 Instead of the expected dienone (52), the catechol derivative (53) was obtained (eq 16). This transformation probably involves three processes: (i) acetylation, (ii) dehydrogenation, and (iii) aromatization. A combination of two effects, steric and inductive, is probably responsible for the angular methyl migration and aromatization sequence. The presence of the C-4 methyl group plays an important role in this rearrangement. A similar rearrangement does not occur in the absence of the C-4 methyl group.

Preparation of Aromatic Bromides.

A mixture of thallium(III) acetate and Bromine in CCl4 is a mild and effective reagent for the bromination of aromatic compounds.24 In addition to experimental simplicity, the reaction is remarkable in that a single pure monobromo isomer is generally obtained and this is the special advantage that the reaction possesses over the vast majority of electrophilic halogenation reactions. Exclusive p-substitution is observed with almost all monosubstituted benzenes. It should be noted that electron-withdrawing groups inhibit the bromination of monosubstituted benzenes. The present method is particularly useful for the preparation of bromides for sensitive substrates such as 9-bromoanthracene (55) (eq 17), 2-bromobiphenylene (57) (eq 18), and 2-bromofluorene (59) (eq 19) from anthracene (54), biphenylene (56), and fluorene (58), respectively. It is concluded from experimental results that the reaction involves bromination by molecular bromine catalyzed by either thallium(III) bromide or thallium(III) acetate.

Thiols to Disulfides.

A number of thiols undergo oxidation by thallium(III) acetate in chloroform.25 As an oxidizing agent, thallium(III) acetate is more effective than lead(IV) acetate or mercury(II) acetate. The conversion of thiols (60) and (61) to disulfides. (62) and (63), respectively, are the typical examples of this oxidation (eqs 20, 21).

Oxidation of p-Toluenesulfonylhydrazones.

Thallium(III) acetate in acetic acid is useful for the regeneration of both aldehydes and ketones from tosylhydrazones.26 The cleavage can be effected at room temperature in the case of aldehydes, but reflux temperature is required for ketones. The reagent can also be used for the regeneration of ketones from semicarbazones. The reaction requires reflux temperature and acetoxylation is a side reaction. The reactivity of thallium(III) acetate has been compared with lead(IV) acetate and mercury(II) acetate.26

a-Acyloxy Carboxylic Acids.

Thallium(III) acetate has been found to react with a number of aliphatic carboxylic acids, yielding a-acyloxy carboxylic acids.27 Thus acetic acid (64) gives acetoxyacetic acid (65) (eq 22). a-Acyloxy carboxylic acids can be hydrolyzed to a-hydroxy acids.

Oxidative Cyclization.

Thallium(III) acetate has played an important role in oxidative cyclizations of o-hydroxyphenyl or o-methoxyphenyl ketones, yielding benzofuran compounds.28 Thus the ketones (66) and (68) are converted to benzofurans (67) and (69), respectively, on heating at 75-85 °C with thallium(III) acetate (3 equiv) in acetic acid (eqs 23, 24). Ketones monosubstituted at the a-carbon give good yields (65-84%), while the unsubstituted and disubstituted ketones give lower yields.

Homoallylic alcohols undergo cyclization, resulting in the formation of tetrahydrofurans.29 Thus the alcohol (70) is converted to tetrahydrofuran (71) by stirring with thallium(III) acetate at rt (eq 25). It was reported30 that various substituted 4-alkenols undergo electrophilic cyclization with thallium(III) acetate, affording a convenient procedure for the synthesis of trans-disubstituted furans. Thus the alkenol (72) produces disubstituted furan (73) in 60-80% yield (eq 26) with only traces of cis-isomer or a tetrahydropyranyl regioisomer. The same reaction using lead(IV) acetate gives (73) in only 31% yield.

Several years ago it was reported31 that ethylene reacts with acetylacetone in acetic acid containing thallium(III) acetate and perchloric acid to yield the furan derivative (74) (eq 27). Similarly, styrene also gives furan derivatives.

1. Meyer, R. J.; Goldschmidt, E. CB 1903, 36, 238.
2. Kochi, J. K.; Bethea, T. W., III JOC 1968, 33, 75.
3. Kabbe, H.-J. LA 1962, 656, 204.
4. Anderson, C. B.; Winstein, S. JOC 1963, 28, 605.
5. Uemura, S.; Miyoshi, H.; Tara, H.; Okano, M.; Ichikawa, K. CC 1976, 218.
6. Uemura, S.; Kitoh, R.; Fujita, K.; Ichikawa, K. BCJ 1967, 40, 1499.
7. Uemura, S.; Miyoshi, H.; Tabata, A.; Okano, M. T 1981, 37, 291.
8. Arzoumanian, H.; Metzger, J. S 1971, 527.
9. Nakano, T.; Maillo, M. A.; Rojas, A. JCS(P1) 1987, 2137.
10. Emmer, G.; Zbiral, E. T 1977, 33, 1415.
11. Glotter, E.; Schwartz, A. JCS(P1) 1976, 1660.
12. Woodward, R. B.; Brutcher, F. V., Jr. JACS 1958, 80, 209.
13. Mangoni, L.; Adinolfi, M.; Barone, G.; Parrilli, M. TL 1973, 4485.
14. Cambie, R. C.; Lindsay, B. G.; Rutledge, P. S.; Woodgate, P. D. CC 1978, 919.
15. Ouellette, R. J.; Shaw, D. L.; South, A., Jr. JACS 1964, 86, 2744.
16. Ouellette, R. J.; Shaw, D. L. JACS 1964, 86, 1651.
17. Campbell, H. M.; Gunn, P. A.; McAlles, A. J.; McCrindle, R. CJC 1973, 51, 4167.
18. Kuehne, M. E.; Giacobbe, T. J. JOC 1968, 33, 3359.
19. Mangeney, P.; Andriamialisoa, R. Z.; Langlois, N.; Langlois, Y.; Potier, P. JACS 1979, 101, 2243.
20. Ortar, G.; Romeo, A. JCS(P1) 1976, 111.
21. Banerjee, A. K.; Carrasco, M. C.; Peña-Matheud, C. A. RTC 1989, 108, 94.
22. Cocker, J. D.; Henbest, H. B.; Phillipps, G. H.; Slater, G. P.; Thomas, D. A. JCS 1965, 6.
23. Ollis, W. D.; Ormand, K. L.; Sutherland, I. O. CC 1968, 1237.
24. McKillop, A.; Bromley, D.; Taylor, E. C. JOC 1972, 37, 88.
25. Uemura, S.; Tanaka, S.; Okano, M. BCJ 1977, 50, 220.
26. Butler, R. N.; Morris, G. J.; O'Donohue, A. M. JCR(M) 1981, 808.
27. Taylor, E. C.; Altland, H. W.; McGillivray, G. TL 1970, 5285.
28. Malaitong, M.; Thebtaranonth, C. CL 1980, 305.
29. Ferraz, H. M. C.; Brocksom, T. J.; Pinto, A. C.; Abla, M. A.; Zocher, D. H. T. TL 1986, 27, 811.
30. Michael, J. P.; Ting, P. C.; Bartlett, P. A. JOC 1985, 50, 2416.
31. Ichikawa, K.; Uemura, S.; Sugita, T. T 1966, 22, 407.

Ajoy K. Banerjee

I.V.I.C., Caracas, Venezuela

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