Tetra-n-butylammonium Bromide1


[1643-19-2]  · C16H36BrN  · Tetra-n-butylammonium Bromide  · (MW 322.43)

(phase-transfer catalyst;1 source of nucleophilic bromide1)

Physical Data: mp 103-104 °C.

Solubility: sol H2O, 1% aq NaOH, CH2Cl2, EtOH; slightly sol toluene; insol 20% aq NaOH.

Form Supplied in: anhydrous white solid.

Analysis of Reagent Purity: tetraalkylammonium salts can be titrated with potassium 3,5-di-t-butyl-2-hydroxybenzenesulfonate and iron(III) chloride.1a

Preparative Methods: several methods are available to recover the quaternary ammonium ion efficiently.1a

Purification: all manipulations should be carried out in a dry-box. The salt can be crystallized from benzene (5 mL g-1) at 80 °C by adding 3 vol of hot hexane and allowing to cool. It can also be purified by precipitation of a saturated solution in dry CCl4 by addition of cyclohexane or by crystallization from a mixture CH2Cl2-Et2O. After filtration, the solid is further dried by heating at 75 °C under vacuo (0.1 mmHg) in the presence of P2O5.2

Handling, Storage, and Precautions: highly hygroscopic; if used in a reaction requiring anhydrous conditions, it should be manipulated in a glove-bag or in a dry-box.

Catalyst for C-X Bond Formation.

Tetrabutylammonium bromide is undoubtedly one of the most widely used phase-transfer catalysts. It combines the lipophilicity required for an efficient phase-transfer catalyst with the hydrophilicity necessary for efficient catalyst recovery. It has been successfully used in the liquid-liquid or solid-liquid phase-transfer alkylation of the NH groups of anilines,3 amides,4 lactams,5 sulfonamides,6 and other nitrogen heterocyclic compounds.7 Sulfur8 and oxygen-containing functional groups9 can also be smoothly alkylated under phase-transfer conditions. Several S-alkylthioacridines have been prepared by liquid-liquid10 or solid-liquid11 phase-transfer catalysis (eq 1).

Carboxylic acids12 and phenols13 can also be alkylated in the presence of tetrabutylammonium bromide. Macrolides can be synthesized by an intramolecular SN2 reaction of a bromo ester via simulated high dilution conditions (eq 2).14

Bu4NBr is also very effective in promoting nucleophilic aromatic substitution reactions to produce aryl thio esters,15 aryl ethers,16 and N-arylbenzodiazepines.17 Some glycosylations were shown to be efficient only in the presence of Bu4NBr.18

Catalyst for Oxidation Reactions.

Phase-transfer oxidation of alcohols to acids,19 alkenes to carboxylic acids,18 sulfides to sulfones,20 and sulfilimines to sulfoximines21 have also been carried out in the presence of tetrabutylammonium bromide along with an oxidizing reagent.

Catalyst for C-C Bond Formation.

The presence of Bu4NBr was shown to be essential in a number of carbon-carbon bond-forming reactions, such as the alkylation of allyl sulfones22 and of Malononitrile,23 and in the lead-promoted Barbier-type reaction of propargyl bromide with aldehydes.24 It has also been used in the efficient synthesis of racemic a-alkyl and a,a-dialkyl a-amino acids by phase-transfer alkylation of Schiff bases (eq 3).25

The presence of Bu4NBr was shown to be necessary to increase the efficiency of some carbon-carbon double bond forming reactions such as Heck-type couplings,26 dehydrohalogenations,27 and Horner-Emmons-Wittig reactions.28

Alkyl and Alkenyl Bromides.

Bu4NBr can be used as a powerful source of bromide for nucleophilic displacement reactions of triflates29 and iodonium salts.30

1. (a) Sjöberg, K. Aldrichim. Acta 1980, 13, 55. (b) Jones, R. A. Aldrichim. Acta 1976, 9, 35. (c) Weber, W. P.; Gokel, G. W. Phase Transfer Catalysis in Organic Synthesis; Springer: New York, 1977. (d) Starks, C. M.; Liotta, C. Phase Transfer Catalysis; Academic: New York, 1978. (e) Dehmlow, E. V.; Dehmlow, S. S. Phase Transfer Catalysis; Verlag Chemie: Deerfield Beach, FL, 1980. (f) Loupy, A.; Tchoubar, B. Salt Effects in Organic and Organometallic Chemistry; VCH: Weinheim, 1992.
2. Perrin, D. D.; Armarego, W. L. Purification of Laboratory Chemicals; 3rd ed.; Pergamon: Oxford, 1988.
3. Ramrao, K. U.; Ramkumar, C. A.; Anant, N. A.; Ramanuja, A. N. SC 1991, 21, 1129.
4. Landini, D.; Penso, M. SC 1988, 18, 791.
5. Reuschling, D.; Pietsch, H.; Linkies, A. TL 1978, 615.
6. Perez, C. F.; Calandri, E. L.; Mazzieri, M. R.; Arguello, B.; Suarez, A. R.; Fumarola, M. J. OPP 1984, 16, 37.
7. (a) Azoles and benzazoles: Diez-Barra, E.; de la Hoz, A.; Sanchez-Migallon, A.; Tejeda, S. H 1992, 34, 1365. (b) Indoles: Barry, J.; Bram, G.; Decodts, G.; Loupy, A.; Pigeon, P.; Sansoulet, J. T 1983, 39, 2669. (c) Pyrazoles: Diez-Barra, E.; de la Hoz, A.; Sanchez-Migallon, A.; Tejeda, S. SC 1990, 20, 2849. (d) Purine and pyrimidines: Hedayatullah, M. SC 1982, 12, 565.
8. Degani, I.; Fochi, R.; Regondi, V. S 1983, 630.
9. For a review on the Bu4NBr catalyzed alkylation of tributylstannyl ethers and acetals, see: David, S.; Hanessian, S. T 1985, 41, 643.
10. (a) Galy, J.-P.; Vincent, E.-J.; Galy, A.-M.; Barbe, J.; Elguero, J. BSB 1981, 90, 947. (b) Vlassa, M.; Kezdi, M.; Goia, I. S 1980, 850.
11. Vlassa, M.; Kezdi, M. OPP 1987, 19, 433.
12. Barry, J.; Bram, G.; Petit, A. H 1985, 23, 875.
13. Gallucci, R. R.; Going, R. C. JOC 1983, 48, 342.
14. Kimura, Y.; Regen, S. L. JOC 1983, 48, 1533.
15. Reeves, W. P.; Bothwell, T. C.; Rudis, J. A.; McClusky, J. V. SC 1982, 12, 1071.
16. Nisato, D.; Sacilotto, R.; Frigerio, M.; Boveri, S.; Boccardi, G. OPP 1985, 17, 75.
17. Essassi, E. M.; Salem, M.; Zniber, R. H 1985, 23, 799.
18. (a) Koto, S.; Morishima, N.; Kusuhara, C.; Sekido, S.; Yoshida, T.; Zen, S. BCJ 1982, 55, 2995. (b) Roy, R.; Tropper, F. SC 1990, 20, 2097.
19. (a) With KMnO4: Herriott, A. W.; Picker, D. TL 1974, 1511. (b) With CrO3: Gelbard, G.; Brunelet, T.; Jouitteau, C. TL 1980, 21, 4653.
20. With NaClO: Trost, B. M.; Braslau, R. JOC 1988, 53, 532.
21. With NaClO: Akutagawa, K.; Furukawa, N. JOC 1984, 49, 2282.
22. Jonczyk, A.; Radwan-Pytlewski, T. JOC 1983, 48, 910.
23. Diez-Barra, E.; de la Hoz, A.; Moreno, A.; Sanchez-Verdu, P. JCS(P1) 1991, 2589.
24. Tanaka, H.; Hamatani, T.; Yamashita, S.; Torii, S. CL 1986, 1461.
25. O'Donnell, M. J.; Wojciechowski, K.; Ghosez, L.; Navarro, M.; Sainte, F.; Antoine, J.-P. S 1984, 313.
26. Carlström, A.-S.; Frejd, T. ACS 1992, 46, 163.
27. Makosza, M.; Lasek, W. T 1991, 47, 2843.
28. Texier-Boullet, F.; Foucaud, A. TL 1980, 21, 2161.
29. (a) Binkley, R. W.; Ambrose, M. G.; Hehemann, D. G. JOC 1980, 45, 4387. (b) Ireland, R. E.; Häbich, D.; Norbeck, D. W. JACS 1985, 107, 3271.
30. (a) Ochiai, M.; Oshima, K.; Masaki, Y. JACS 1991, 113, 7059. (b) Ochiai, M.; Oshima, K.; Masaki, Y. TL 1991, 32, 7711.

André B. Charette

Université de Montréal, Québec, Canada

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