Cesium Carbonate


[534-17-8]  · CCs2O3  · Cesium Carbonate  · (MW 325.82)

(used in the synthesis of crown ethers and macrocycles;1 catalyzes the Horner-Emmons cyclization;2 used as base for alkylations3)

Physical Data: mp 610 °C (dec).

Solubility: sol water, alcohol, ether.

Form Supplied in: white powder; widely available.

Purification: crystallized from ethanol (10 mL g-1) by slow evaporation.

Handling, Storage, and Precautions: irritant; handle with gloves; hygroscopic; keep away from moisture; flush eyes or skin with copious amounts of water in case of contact; possible mutagen; avoid inhalation.

Macrocyclization Reagent.

Crown ethers, generally used as ionophores for various applications, can be prepared by using Cs2CO3. This reagent serves as both a base and a cation template in the macrocylization of dicarboxylic acids and a,o-alkyl dihalides to generate crown ethers.1,5 For example, a crown ether is produced in 85% yield when dicesium pyridine-3,5-dicarboxylate, generated from the acid and Cs2CO3, reacts with 1,11-dibromo-3,6,9-trioxoundecane in DMF upon heating the reaction mixture between 60-70 °C for 48 h (eq 1). Under similar conditions, aromatic dicarboxylic acids afford related crown ethers. This procedure also works well for crown ethers prepared from salicylic acid and bromopolyethylene glycols.1

Thia crown ethers can also be prepared with Cs2CO3. Yields for these reactions are consistently good (45-95%) when the cesium salts of a,o-dithiols are treated with a,o-dihalides in DMF (eq 2).5 Much lower yields (1-20%) are obtained if other methods, such as high dilution techniques, are used in the absence of a cesium counterion. Similar chemistry has been used to prepare functionalized cyclophane derivatives by replacing the a,o-dihalide with 1,3-dichloroacetone and using o-xylylenedithiol as the a,o-dithol.6

Chiral crown ethers have also been prepared by using Cs2CO3. A chiral diol and chiral ditosylate, both prepared from (R,R)-(+)-hydrobenzoin, have been coupled using NaH as a base and Cs2CO3 as a template in DMF (eq 3).7

Tosylamides have been used to prepare aza macrocycles with Cs2CO3. The bicarbonate salt (CsHCO3) is not basic enough to deprotonate ditosylamides.8 Also, carboxamides and urethanes do not react as efficiently with Cs2CO3 as do tosylamides. Among the alkali bases, Cs2CO3 provided consistently higher yields than Lithium Carbonate, Sodium Carbonate, Potassium Carbonate and Rb2CO3. A typical example involved treating 1,10-bis[(p-tolylsulfonyl)amino]decane with two equivalents of Cs2CO3 in dry DMF followed by the addition of 1,6-dibromohexane and stirring the mixture at room temperature for 24 h to give the aza macrocycle in 72% yield. Reduction with sodium amalgam in buffered methanol gave the cyclic diamine (eq 4).

Cs2CO3 has been used to prepare derivatized calix[4]arenes for use as lipophilic, water-soluble, and ionophoric receptors.9 The calix[4]arene cone structure depends on the type of base used for alkylation of the phenolic hydroxyl groups. For example, a cone is generated when NaH is the base during alkylation of the calix[4]arene with ethyl bromoacetate in acetone. When Cs2CO3 is used, a 1,3-alternate cone is obtained, whereas a partial cone is formed when K2CO3 is used.9

Carcerands and carceplexes have been prepared by using Cs2CO3. For example, mixing a tetrathiol, a tetrachloride, and pulverized Cs2CO3 in DMF/THF under high dilution conditions afforded the carcerand.10 FAB-MS of the product indicated that the cesium ion served as a template.

Lactonizations can be accomplished using Cs2CO3 and o-bromocarboxylic acids at 40 °C in DMF.4b,11 These conditions afford mixtures of lactones and diolides with their product distribution depending on the ring size. Cs2CO3 has been used in a macrocyclization reaction to generate steroids under anionic conditions.12

Horner-Emmons Base.

The Horner-Wadsworth-Emmons reaction is sensitive when the carbonyl component contains acidic hydrogens, such as hydroxyl groups. This problem can be circumvented by using Cs2CO3 as the base. The method is somewhat dependent on the type of solvent used and the degree of hydration of Cs2CO3 (eq 5).2 NaH has also been replaced with Cs2CO3 in a synthesis of D-erytho-C18-sphingosine using a Wittig-Horner reaction.13 A tandem Wittig-Michael reaction in which a lactol is treated with dimethyl phosphonoacetate in the presence of Cs2CO3 has been reported (eq 6).14 An intermolecular Michael addition of a cyclic b-keto ester to an a,b-ynone has been accomplished with Cs2CO3 in 89% yield.15 An intramolecular Diels-Alder reaction using Cs2CO3 and paraformaldehyde in THF has been used to produce the neurotoxic toxin slaframine from an amide.16

Alykylation Base.

Esterification under mild conditions can be accomplished with Cs2CO3 or CsHCO3.3 For example, amino acid and peptide esters can be made by generating the cesium salt of the corresponding carboxylic acid followed by treating the salt with an alkyl halide in DMF (eq 7).

Mono-C-alkylation of b-dicarbonyl compounds is complicated by competitive O-alkylation and dialkylation reactions.17 C-Alkylation of 2,4-pentanedione has been achieved with Iodomethane in 75% yield using K2CO3 as a base. The use of Cs2CO3 by itself, or in combination with K2CO3, allows for improved monoalkylation reactions using higher molecular weight alkyl halides (eq 8).18 Phenolates generated with Cs2CO3 are alkylated with Dimethyl Sulfate in 94% yield.19

Dibenzyl carbonate is prepared in 63-70% yield when Cs2CO3 is treated with Benzyl Chloride at 100-110 °C for 12 h.20 Cs2CO3 has also been used to mediate Michael additions of glycine esters. Treating a Schiff base of glycine and an enone with 10 mol % Cs2CO3 gives substituted prolines in 60-78% yield after hydrogenation (eq 9).21 Replacement of NaH with 5-10 mol% Cs2CO3 under standard Schmidt conditions in the preparation of trichloroacetimidates allows for large scale preparation of O-a-cellobiosyl trichloroacetimidate heptacetate in good yield.22

Cleavage of aryl esters has been accomplished using either Cs2CO3 or CsHCO3. For example, refluxing resorcinol dibenzoate in DME for 24 h with 1.5 equiv Cs2CO3 produces the monobenzoate in greater than 95% yield.23 Cs2CO3 and Di-t-butyl Dicarbonate cleave 2-oxazolidinones at 25 °C in MeOH to give Boc-amino alcohols in 70% yield (eq 10).24

1. van Keulen, B. J.; Kellogg, R. M.; Piepers, O. CC 1979, 285.
2. (a) Mouloungui, Z.; Murengezi, I.; Delmas, M.; Gaset, A. SC 1988, 18, 1241. (b) Mouloungui, Z.; Delmas, M.; Gaset, A. JOC 1989, 54, 3936.
3. Wang, S.-S.; Gisin, B. F.; Winter, D. P.; Makofske, R.; Kulesha, I. D.; Tzougraki, C.; Meienhofer, J. JOC 1977, 42, 1286.
4. (a) Piepers, O.; Kellogg, R. M. CC 1978, 383. (b) Kruizinga, W. H.; Kellogg, R. M. CC 1979, 286.
5. (a) Buter, J.; Kellogg, R. M. CC 1980, 466. (b) Vögtle, F.; Klieser, B. S 1982, 294.
6. Chiu, J.-J.; Grewal, R. S.; Hart, H.; Ward, D. L. JOC 1993, 58, 1553.
7. Crosby, J.; Stoddart, J. F.; Sun, X.; Venner, M. R. W. S 1993, 141.
8. Vriesema, B. K.; Buter, J.; Kellogg, R. M. JOC 1984, 49, 110.
9. (a) Iwamoto, K.; Fujimoto, K.; Matsuda, T.; Shinkai, S. TL 1990, 31, 7169. (b) Shinkai, S.; Fujimoto, K.; Otsuka, T; Ammon, H. L. JOC 1992, 57, 1516.
10. (a) Cram, D. J.; Karbach, S.; Kim, Y. H.; Baczynskyj, L.; Marti, K.; Sampson, R. M.; Kalleymeyn, G. JACS 1988, 110, 2554. (b) Cram, D. J.; Karbach, S.; Kim, Y. H.; Baczynskyj, L.; M.; Kalleymeyn, G. W. JACS 1985, 107, 2575.
11. (a) Barbier, M. CC 1982, 668. (b) Kruizinga, W. H.; Kellogg, R. M. JACS 1981, 103, 5183.
12. Lavallée, J.-F.; Deslongchamps, P. TL 1988, 29, 6033.
13. Yamanoi, T.; Akiyama, T.; Ishida, E.; Abe, H.; Amemiya, M.; Inazu, T. CL 1989, 335.
14. Bloch, R.; Seck, M. TL 1987, 28, 5819.
15. (a) Lavallée, J.-F.; Berthiaume. G.; Deslongchamps, P.; TL 1986, 27, 5455. (b) Lavallée, J.-F.; Deslongchamps, P. TL 1987, 28, 3457.
16. Gobao, R. A.; Bremmer, M. L.; Weinreb, S. M. JACS 1982, 104, 7065.
17. House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo Park, CA, 1972.
18. Shrout, D. P.; Lightner, D. A. SC 1990, 20, 2075.
19. Winters, R. T.; Sercel A. D.; Showalter, H. D. H. S 1988, 712.
20. Cella J. A.; Bacon, S. W. JOC 1984, 49, 1122.
21. van der Werf, A.; Kellogg, R. M. TL 1991, 32, 3727.
22. Urban F. J.; Moore, B. S.; Breitenbach, R. TL 1990, 31, 4421.
23. Zaugg, H. E. JOC 1976, 41, 3419.
24. Ishizuka, T.; Kunieda, T. TL 1987, 28, 4185.

Mark R. Sivik

Procter & Gamble, Cincinnati, OH, USA

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