Tetra-n-butylammonium Hydroxide

n-Bu4NOH

[2052-49-5]  · C16H37NO  · Tetra-n-butylammonium Hydroxide  · (MW 259.54)

(quaternary ammonium salt; strong base; phase-transfer catalyst1)

Alternate Name: TBAH.

Solubility: sol most organic solvents (alcohols, hydrocarbons, aromatics, halogenated solvents), H2O.

Form Supplied in: 40 wt % solution in H2O; 1.0 M solution in MeOH. A typical impurity is tributylamine.

Analysis of Reagent Purity: aqueous titration with HCl versus phenolphthalein;2 nonaqueous titration with benzoic acid in pyridine and thymol blue indicator.3

Preparative Method: prepared in situ from ammonium halides.2

Handling, Storage, and Precautions: methanol solution is hygroscopic; highly toxic; may decompose on heating.4

Alkylations.

Tetrabutylammonium hydroxide (1) has been used to effect a variety of organic transformations. A strongly basic catalyst, (1) was able to promote alkylation (eq 1)5 and arylation6 of nitroalkanes under phase-transfer conditions. The intermediate tetrabutylammonium aci-nitronates generated were more reactive than the corresponding lithium salts.

The monoalkylation of cyanomethanephosphonic diamides was reported to occur with high selectivity and good yield (eq 2).7 Strong amide bases or Sodium Hydride led to formation of mixtures of mono- and dialkylation products. Alkylations of other active hydrogen compounds have been studied.8

The selective monobenzylation of an indole nitrogen under phase-transfer conditions proceeds in better than 95% yield for a variety of substrates (eq 3).9 The reaction is procedurally simple when compared to the alkylation of the dianion normally generated under anhydrous conditions with n-Butyllithium (Hexamethylphosphoric Triamide, THF, 0 °C), which produces only a 60% yield of product.

An extension of this chemistry is seen in the intramolecular alkylations of nitrogen which have been reported in the preparation of dihydropyridones (eq 4).10

Tetrabutylammonium hydroxide has also been used in the Robinson annulation of dihydrocarvone with Methyl Vinyl Ketone in 63% yield, which is reported to improve upon other methods.11 Dehydration does not occur in the reaction and workup is simplified (eq 5). Similarly, intramolecular Horner-Emmons closure of an activated phosphono ester was used in the synthesis of (±)-silphinene (eq 6).12

Dehydrations.

Vicinal dihydro diols of polycyclic aromatic hydrocarbons such as the benzo[a]pyrene derivative (2) were dehydrated under mild conditions by treatment with TBAH in methanol (eq 7).13 Alkali hydroxides did not effect the reaction in these cases without a catalyst present (crown ether or ammonium salt), and methanol was necessary as solvent. The regioselectivity for the dehydration (3:4 = 13:87) was opposite to that from a Phosphoric Acid-catalyzed dehydration (3:4 = 97:3). The base-catalyzed reaction did not proceed for substrates which lacked aromatization capability. A patent has been obtained for the monodehydration of a fluorinated dihydroxybenzene under similar conditions.14

Carbenes.

The reaction of (1) with Chloroform under phase-transfer conditions is a good method for generating dichlorocarbene.1c This reaction was used to cleanly generate aldehyde (6) from dehydronuciferene (5), which is nucleophilic enough to attack dichlorocarbene (eq 8).15 In contrast, compound (5) could not be alkylated with Iodomethane.

A phase-transfer reaction mediated by tetrabutylammonium hydroxide was found to be most suitable for the halo lactonization of alkynoic acids to prepare halo enol lactones (eq 9).16 The reaction was carried out with halosuccinimides in the presence of catalytic TBAH, and yields of 70-93% were obtained.


1. For reviews of phase transfer reactions, see (a) Keller, W. E. Phase Transfer Reactions. Fluka Compendium; Thieme Verlag: Stuttgart, 1986; Vols. 1 and 2. (b) Dehmlow, E. V. Phase Transfer Catalysis; Verlag Chemie: Deerfield Beach, FL, 1980. (c) Starks, C. M.; Liotta, C. Phase Transfer Catalysis, Principles and Techniques; Academic: New York, 1978. (d) Dockx, J. S 1973, 441. (e) Dehmlow, E. V. AG(E) 1974, 13, 170. For a mechanistic review of hydroxide-mediated reactions under PTC conditions, see: (f) Rabinovitz, M.; Cohen, Y.; Halpern, M. AG(E) 1986, 25, 960.
2. (a) In alcohol using silver oxide and Bu4I: Cluett, M. L. Anal. Chem. 1959, 31, 610. (b) In alcohol using ion exchange resin and Bu4I: Harlow, G. A.; Noble, C. M.; Wyld, G. E. A. Anal. Chem. 1956, 28, 787.
3. Gandrud, B. W.; Lazrus, A. L. Anal. Chem. 1983, 55, 988.
4. Smith, P. A. S.; Frank, S. JACS 1952, 74, 509. See also Dehmlow, E. V.; Knufinke, V. JCR(S) 1989, 224 for a study on the stability and performance of various phase transfer catalysts.
5. Burt, B. L.; Freeman, D. J.; Gray, P. G.; Norris, R. K.; Randles, D. TL 1977, 3063.
6. Norris, R. K.; Randles, D. AJC 1979, 32, 2413.
7. Blanchard, J.; Collignon, N.; Savignac, P.; Normant, H. S 1975, 655.
8. For malonates, benzyl nitrile, and benzyl methyl ketone, see, for example: Brändström, A.; Junggren, U. TL 1972, 473. For cyclic diketones, see: Kagechika, K.; Shibasaki, M. JOC 1991, 56, 4093.
9. de Silva, S. O.; Snieckus, V. CJC 1978, 56, 1621.
10. Zvonok, A. M.; Kuz'menok, N. M.; Stanishevskii, L. S. KGS 1988, 1022.
11. Chen, E. Y. SC 1983, 13, 927.
12. Rao, Y. K.; Nagarajan, M. TL 1988, 29, 107.
13. McCourt, D. W.; Roller, P. P.; Gelboin, H. V. JOC 1981, 46, 4157.
14. Ryback, G. U.S. Patent 4 855 512, 1989 (CA 1989, 110, 134 878r).
15. Saá, J. M.; Cava, M. P. JOC 1977, 42, 347.
16. Krafft, G. A.; Katzenellenbogen, J. A. JACS 1981, 103, 5459.

Mary Ellen Bos

The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA



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