Benzyltrimethylammonium Hydroxide

[100-85-6]  · C10H17NO  · Benzyltrimethylammonium Hydroxide  · (MW 167.25)

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

Alternate Name: Triton® B.

Physical Data: none available (generally obtained in solution).

Solubility: sol water, alcohols, hydrocarbons, aromatic hydrocarbons, halogenated solvents.

Form Supplied in: 40 wt % in H2O; 35-40 wt % in MeOH (Triton B). Typical impurities are amines or benzyl alcohol.

Purification: 2 methanol solution can be decolorized with charcoal, concentrated to a syrup, and dried under vacuum at 75 °C and 1 mmHg pressure. Anhydrous reagent is obtained by drying over P2O5 in a vacuum desiccator.

Handling, Storage, and Precautions: hygroscopic solutions; highly toxic; decomposition can occur on heating.3

Epoxidations.

Benzyltrimethylammonium hydroxide (1) is a common reagent in organic synthesis. It finds use as a catalytic base in the epoxidation of a,b-unsaturated ketones with t-Butyl Hydroperoxide,4 as demonstrated in a step toward the total synthesis of a complex anthracyclinone (eq 1).5 The combination of Triton B and either t-BuOOH or Hydrogen Peroxide has been used to advantage in situations where conventional epoxidation conditions have proven either destructive6 or ineffective.7 Epoxidations of other a,b-unsaturated systems, such as sulfonates,8 have also been reported.

Oxidations at Activated Methylenes.

Benzyltrimethylammonium hydroxide has been used as a catalyst for the oxidation of methylene and/or methine groups. The oxidation of a tricyclic ketone to an anthraquinone was accomplished in good yield using this approach (eq 2).9 Similarly, benzylic anions have been generated and efficiently trapped with air in DMSO.10

Dehydrohalogenation.

A variety of 1-bromoalkynes have been prepared through the action of Triton B on 1,1-dibromoalkenes.11 Both aryl and alkyl substituents were examined, with recoveries ranging from 35 to 87%, and generally above 60% yield (eq 3).

In an extension of this reaction, a synthesis of propargyl amines using Triton B was developed in which 1,1-dibromoalkenes were dehydrohalogenated, isomerized in situ to bromoallenes, and subjected to nucleophilic attack by primary or secondary amines (eq 4).12 Yields ranged from 5 to 88%. Attack by methanol was also examined; however, yields were generally low.

Aldol Condensations.

The aldol reaction has often been carried out with Triton B functioning as base. In the synthesis of a cytochalasin intermediate, a seven-membered ring was closed under the action of Triton B in excellent yield (eq 5).13 The reagent can effect the double aldol condensation of dibenzyl ketone with benzil, producing tetraphenylcyclopentadienone in excellent yield (eq 6).14

The action of Triton B has been used in the synthesis of 2-thiomethylindoles (eq 7).15 Condensation of various 2-sulfonamido aldehydes with methyl methylsulfinylmethyl sulfide (55-88%) followed by treatment with H2S and HCl gave rise to the indole products (62-80%).

Conjugate Additions.

Triton B is an effective catalyst for the conjugate addition of carbon acids to Michael acceptors. Such is the case with the reaction of nitromethane and t-butyl acrylate mediated by a methanolic solution of (1) (eq 8).16 In the given example, the triester formed was used in the preparation of dendritic macromolecules. Other bases were not as effective.17 Nitroalkanes have also been added intramolecularly to alkynylamides18 and intermolecularly to a variety of unsaturated systems. The addition of a benzonitrile to methyl acrylate in a Michael fashion was reported to occur in excellent yield (eq 9).19 Heteroatomic nucleophiles have also been added in a 1,4-fashion to conjugated systems.20

The addition of nucleophiles to vinylsiloxycyclopropanecarboxylates catalyzed by Triton B was reported to be an efficient method for the preparation of functionalized 4-oxoalkanoates (eq 10).21 Other catalysts were not as effective.

Benzyltrimethylammonium hydroxide also has been utilized in steroid syntheses through the Torgov reaction.22 A cyclic 1,3-diketone can be C-alkylated through a formal SN2 displacement of an ionizable tertiary hydroxy group (eq 11). Alkylation of 1,3-diketones with halides is also well known.23

Eq 12 shows a novel photolytic reaction in which Triton B was used to improve the conversion of an amino enone into a bridged bicyclic compound.24

Benzyltrimethylammonium hydroxide has also been used in the conversion of an a-hydroxy-1,1-dichloride to an aldehyde, which was cyclized to generate the tetracyclic compound rhodomycinone (eq 13).25


1. For reviews of phase transfer reactions, see (a) Keller, W. E. Phase Transfer Reactions. Fluka Compendium; Thieme: 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. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988.
3. Collie, N.; Schryver, S. B. JCS 1890, 767. See also note on stability under Methyltrioctylammonium Chloride.
4. Yang, N. C.; Finnegan, R. A. JACS 1958, 80, 5845.
5. Hauser, F. M.; Chakrapani, S.; Ellenberger, W. P. JOC 1991, 56, 5248.
6. Ireland, R. E.; Wuts, P. G. M.; Ernst, B. JACS 1981, 103, 3205.
7. Asaoka, M.; Hayashibe, S.; Sonoda, S.; Takei, H. TL 1990, 31, 4761.
8. Carretero, J. C.; Ghosez, L. TL 1987, 28, 1101.
9. Kende, A. S.; Rizzi, J. P. JACS 1981, 103, 4247. Wulff, W. D.; Tang, P. C. JACS 1984, 106, 434.
10. Finger, C. S 1970, 541.
11. Bestmann, H. J.; Frey, H. LA 1980, 2061.
12. Frey, H.; Kaupp, G. S 1990, 931.
13. Pyne, S. G.; Spellmeyer, D. C.; Chen, S.; Fuchs, P. L. JACS 1982, 104, 5728.
14. Fieser, L. S. OSC 1973, 5, 604.
15. Hewson, A. T.; Hughes, K.; Richardson, S. K.; Sharpe, D. A.; Wadsworth, A. H. JCS(P1) 1991, 1565.
16. Newkome, G. R.; Behera, R. J.; Moorefield, C. N.; Baker, G. R. JOC 1991, 56, 7162.
17. Weis, C. D.; Newkome, G. R. JOC 1990, 55, 5801.
18. Patra, R.; Maiti, S. B.; Chatterjee, A.; Chakravartu, A. K. TL 1991, 32, 1363.
19. Cheng, A.; Uyeno, E.; Polgar, W.; Toll, L.; Lawson, J. A.; DeGraw, J. I.; Loew, G.; Cammerman, A.; Cammerman, N. JMC 1986, 29, 531; and references therein.
20. Examples of oxygen nucleophiles: Dasaradhi, L.; Fadnavis, N. W.; Bhalerao, U. T. CC 1990, 729. Nitrogen nucleophiles: Pyne, S. G.; Chapman, S. L. CC 1986, 1688. Sulfur nucleophiles: Kharasch, M. S.; Fuchs, C. F. JOC 1948, 13, 97. Stewart, J. M.; Klundt, I.; Peacock, K. JOC 1960, 25, 913.
21. Grimm, E. L.; Zschiesche, R.; Reissig, H. U. JOC 1985, 50, 5543.
22. Ananchenko, S. N.; Torgov, I. V. TL 1963, 1553. Lehmann, G.; Wehlan, H.; Hilgetag, G. CB 1967, 100, 2967. Douglas, S. P.; Sawyer, J. F.; Yates, P. TL 1985, 26, 5955.
23. Mori, K.; Mori, H. OS 1990, 68, 56; OSC 1993, 8, 312.
24. Kraus, G. A.; Chen, L. TL 1991, 32, 7151.
25. Krohn, K.; Priyono, W. T 1984, 40, 4609.

Mary Ellen Bos

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



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