Methyltrioctylammonium Chloride-Alkali

[5137-55-3]  · C25H54ClN  · Methyltrioctylammonium Chloride  · (MW 404.25)

(quaternary ammonium salt; phase transfer catalyst1)

Alternate Names: Aliquat® 336; tricaprylylmethylammonium chloride.

Physical Data: d 0.884 g cm-3.

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

Form Supplied in: neat liquid; amines are typical impurities.

Purification: toluene solutions (30% by weight) can be washed either twice with equal volumes of 1.5 M HBr solution2 or three times with equal volumes 4 N NaOH followed by three washes with 1.5 M HCl.3

Handling, Storage, and Precautions: hygroscopic; highly toxic; may decompose on prolonged heating (see below).

Introduction.

Methyltrioctylammonium chloride (1) has found widespread use in organic synthesis. Typical of phase transfer reagents, (1) has been used in dehydrohalogenation, alkylation, saponification, conjugate addition, and carbene reactions. As a caution on catalyst stability and performance, it should be noted that (1) has a half-life of 34 h at 110 °C in chlorobenzene, decomposing to a 2:3 mixture of (Oct)2NMe and (Oct)3N via Hofmann elimination or dealkylation. Under strongly basic conditions (50% Sodium Hydroxide, PhCl, 60 °C), decomposition is more rapid (t1/2 = 9 h), with a greater percentage of Hofmann product formed (95:5).4

Carbonyl Transformations.

Saponification of esters can be carried out either in solution5 or under solvent-free conditions.6 In the latter case, isolated yields of acids from hindered esters were comparable or better than other methods (eq 1). Similarly, ester formation may be carried out without solvent, but Potassium Carbonate is preferable to Potassium Hydroxide as saponification does not occur.

Alkylations.

At Heteroatoms.

Methyltrioctylammonium chloride (1) has been used to effect phase transfer alkylation of phenols,7 alcohols,8 and thiols.9 Care must be taken in solvent choice, as the use of dichloromethane can give rise, under basic conditions, to the formation of acetals (eq 2)10 or thioacetals7 in excellent yields (90 +%).

The reaction may be carried out intramolecularly for the preparation of oxetanes1a or b-lactams.11

At Carbon.

Substrates bearing acidic protons may be alkylated under phase transfer catalysis (PTC) conditions. For example, cyclopropane-1,1-dicarboxylates have been prepared in 75-91% yields using 1,2-dichloroethane (eq 3).12 Although catalytic water is necessary for the reaction to proceed, large amounts reduce yields. Reactions carried out under solid/liquid phase transfer conditions suffer less from side reactions such as product saponification than those using aqueous solutions of base. For similar reasons, K2CO3 is preferred over KOH in the reaction. Alternatively, if cyclopropanecarboxylic acid products are desired, saponification may be carried out in situ.13

Alkynes can be deprotonated under PTC conditions (eq 4), and the resulting anions can be trapped.14 Simple ketones may be alkylated by the combination of (1) and potassium hydroxide (eq 5),15 and a-protons can be exchanged for deuterium in the presence of NaOD/D2O.16 Preparation of hydroxycyclopentenones was carried out by the reaction of (1) with a keto aldehyde in the presence of Lithium Hydroxide (eq 6).17

Carbene Chemistry.

Preparation of dichlorocarbene under phase transfer conditions is well known;1c (1) is an effective catalyst for the formation of this reactive species,15 as exemplified in eq 7.18

Miscellaneous.

The Ramberg-Bäcklund reaction of a-halo sulfones has been catalyzed by (1) and 10% NaOH solution in excellent yields. A single-pot reaction sequence in which a sulfone is halogenated and rearranged was also described (eq 8).19

An improved method of a-diazocarbonyl preparation was reported using (1).20 The method typically produces diazo compounds of high purity, free from starting material and in excellent yield (eq 9).

Related Reagents.

See the entries for benzyltriethylammonium, benzyltrimethylammonium, tetrabutylammonium, tetraethylammonium, and tetramethylammonium salts.


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.; Dehmlow, S. S. Phase Transfer Catalysis, 2nd ed.; Verlag Chemie: Deerfield Beach, FL, 1983. (c) Starks, C. M.; Liotta, C. Phase Transfer Catalysis, Principles and Techniques; Academic: New York, 1978. (d) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-Transfer Catalysis: Fundamentals, Applications, and Industrial Perspectives; Chapman & Hall: New York, 1994. (e) Dockx, J. S 1973, 441. (f) Dehmlow, E. V. AG(E) 1974, 13, 170. For a mechanistic review of hydroxide-mediated reactions under PTC conditions, see: (g) Rabinovitz, M.; Cohen, Y.; Halpern, M. AG(E) 1986, 25, 960.
2. Petrow, H. G.; Allen, R. J. Anal. Chem. 1961, 33, 1303.
3. Petrow, H. G.; Lindstrom, R. Anal. Chem. 1961, 33, 313.
4. Dehmlow, E. V.; Knufinke, V. JCR(S) 1989, 224.
5. Dehmlow, E. V.; Barahona-Naranjo, S. JCR(S) 1979, 238.
6. Loupy, A.; Pedoussaut, M.; Sansoulet, J. JOC 1986, 51, 740.
7. van Heerden, F. R.; van Zyl, J. J.; Rall, G. J. H.; Brandt, E. V.; Roux, D. G. TL 1978, 661.
8. Barry, J.; Bram, G.; Decodts, G.; Loupy, A.; Pigeon, P.; Sansoulet, J. T 1984, 40, 2945.
9. Herriott, A. W.; Picker, D. S 1975, 447.
10. Dehmlow, E. V.; Schmidt, J. TL 1976, 95.
11. Meegan, M. J.; Fleming, B. G.; Walsh, O. M. JCR(S) 1991, 156.
12. Heiszman, J.; Bitter, I.; Harsányi, K.; Tőke, L. S 1987, 738.
13. Singh, R. K.; Danishefsky, S. JOC 1975, 40, 2969.
14. Potapov, V. A.; Amosova, S. V.; Kashik, A. S. TL 1989, 30, 613.
15. Naf, F.; Decorzant, R. HCA 1978, 61, 2524.
16. Starks, C. M. JACS 1971, 93, 195.
17. Kieczykowski, G. R.; Pogonowski, C. S.; Richman, J. E.; Schlessinger, R. H. JOC 1977, 42, 175.
18. Adam, W.; Birke, A.; Cádiz, C.; Díaz, S.; Rodríguez, A. JOC 1978, 43, 1154.
19. Hartman, G. D.; Hartman, R. D. S 1982, 504.
20. Ledon, H. S 1974, 347.

Mary Ellen Bos

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



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