[280-57-9]  · C6H12N2  · 1,4-Diazabicyclo[2.2.2]octane  · (MW 112.20)

(forms crystalline organometallic complexes;2 selective base catalyst for Baylis-Hillman reaction;3 can activate sodamide;4 cleaves esters selectively;5 transalkylating agent;6 dehydrohalogenating agent;7 pyrolysis catalyst;8 nucleophilic acylating agent;9 additive for trialkyl borohydrides;10 reagent in miscellaneous reactions11-13)

Alternate Names: DABCO; triethylenediamine; TED.

Physical Data: mp 161 °C (subl. sample); bp 174 °C; fp 62 °C; d 1.14 g cm-3.

Solubility: (g/100g of the solvent at 25 °C): water 45, ethanol 77, benzene 51, acetone 13, ethyl methyl ketone 26.

Form Supplied in: colorless crystalline compound; commercially available.

Analysis of Reagent Purity: HCl titration.

Purification: purified by either vacuum sublimation or azeotropic distillation with benzene followed by recrystallization from petroleum ether or methanol-ethyl ether (1:1).

Handling, Storage, and Precautions: is extremely hygroscopic, corrosive, and readily sublimes at room temperature. This reagent should be stored at 0-5 °C under nitrogen. Moderately toxic by ingestion or inhalation; skin and eye irritant. Use in a fume hood.

Crystalline Organometallic Complexes.

DABCO forms stable and crystalline complexes with organometallic compounds of Li, Zn, and Mg in hydrocarbon solvents.2 The organolithium complexes are particularly useful in promoting inert metalations of aromatic hydrocarbons.14 An interesting application of the DABCO-BuLi complex is the quantitative lithiation of thioanisole to phenylthiomethyllithium and its subsequent use in homologation of primary alkyl bromides and iodides (eq 1).15,16

Catalyst for Baylis-Hillman Reaction.

DABCO is a very effective catalyst for the Baylis-Hillman reaction17 of a,b-unsaturated vinylic systems with electrophiles (e.g. aldehydes) to produce a-substituted acrylates (eq 2).3,18,19

These typically slow reactions can be accelerated by increasing the molar proportions of DABCO or by varying experimental conditions, or even by use of microwave energy.19-21 The asymmetric Baylis-Hillman reaction with a variety of chiral auxiliaries is also effectively catalyzed by DABCO (eqs 3-5).22 -24 The use of DABCO with chiral (arylaldehydeimine)tricarbonylchromium complexes significantly enhances the yields and diastereoselectivity (eq 6).25

Activation of Sodamide.

DABCO remarkably enhances the reactivity of sodamide in the Haller-Bauer cleavage of nonenolizable ketones to the corresponding carboxamides (eq 7).4,26

Selective Cleavage of Esters.

DABCO is a selective reagent for the single-pot dealkoxycarbonylation of b-keto esters, geminal diesters, and a-sulfonyl(alkyl)malonic esters.5,27,28 Good selectivity was noticed with b-keto esters (eq 8) and geminal diesters (eq 9), which gave ketones and monoesters, respectively. The deethoxycarbonylation of a-sulfonyl(alkyl)malonic esters in presence of DABCO is a competitive reaction with desulfonylation and is dependent on the size of alkyl groups (eqs 10, 11).28 As the alkyl group changes from methyl to benzyl to phenyl, more desulfonation than deethoxycarbonylation is observed. This method is very effective for the cleavage of esters over conventional methods, which are essentially multi-step.

Transalkylating Agent.

The exposed lone pair of electrons and interactions between the nitrogen atoms of DABCO, which are separated by only 2.5 Å, are the key factors in the transalkylation reactions with quaternary ammonium salts (eq 12).6

Dehydrohalogenating Agent.

The Ramberg-Bäcklund rearrangement of a,a-dichlorobisbenzyl sulfones to the corresponding 2,3-diphenylthiirene 1,1-dioxides involves dehydrohalogenation and can be achieved very effectively by stirring with DABCO in DMSO at rt (eq 13).7

DABCO is also effective in the dehydrobromination of substituted dibromocyclohexanones to the corresponding cyclohexadienes (eq 14).29

As a Pyrolysis Catalyst.

DABCO is very effective among the tertiary amines studied for the pyrolysis of vinyl azides.8 The products are 1-azirines and are obtained in 44-95% yields (eq 15). Use of aprotic solvents with DABCO decreases the yields.

As a Nucleophilic Acylating Agent.

Its action as a nucleophilic acylation catalyst is significant in the formation of a large number of cyanohydrin esters from a-keto nitriles and aldehydes (eqs 16, 17).9 The homogeneous, mild, and safe experimental conditions make this method very attractive over the two-phase PTC methods with use of excess cyanide ion.30 Commercially useful 6-O-acylsucroses were synthesized by the DABCO-catalyzed regioselective acylation of sucrose with 3-acyl-5-methyl-1,3,4-thiadiazole-2(3H)-thiones (eq 18).31

As an Additive for Trialkylborohydrides.

Alkali metal trialkylborohydrides (Li and Na) with bulky alkyl groups are useful chiral reducing agents for carbonyl compounds. These hydrides can be prepared in high yield by the reaction of trialkylboranes with Lithium Aluminum Hydride or with NaEt2AlH2 in presence of DABCO (eqs 19, 20). The role of DABCO is to precipitate AlH3 and Et2AlH from the reaction medium.10,32

As a Catalyst in Miscellaneous Reactions.

DABCO effects singlet oxygen quenching very efficiently without undergoing any chemical change.11 It is a selective basic catalyst for the reaction of phenyl isocyanate with polyhydric alcohols to form polyurethanes.12 DABCO is particularly effective as a base catalyst in the Michael addition reactions of a,b-unsaturated ketones with b-keto thiolesters and S,S-diethyl dithiomalonate (eqs 21, 22).13 The reaction is so specific to the base catalyst that the use of strong bases did not result in any product formation. Recently its use as a base in the phospha-Witting reaction to form C-P double bonds was also reported (eq 23).33

As a electron-donor reagent it forms a variety of useful adducts and complexes. The DABCO-2Br2 complex (mp 155-60 °C, stable to air, light, and water) is a selective reagent for the oxidation of benzylic and secondary hydroxyls,34 and for sulfides.35 The DABCO-2H2O2 complex is an equivalent to anhydrous Hydrogen Peroxide.36 This on treatment with Chlorotrimethylsilane gives Bis(trimethylsilyl) Peroxide, a useful reagent for the electrophilic hydroxylation of aromatic and heteroaromatic systems37 and also for the facile conversion of sulfones to carbonyl compounds.38

1. (a) Mosby, W. L. Heterocyclic Systems with Bridgehead Nitrogen Atoms; Interscience: New York, 1961; Part 2, Chapter XVII, pp 1372-75. (b) Yakhontov, L. N.; Mrachkovskaya, L. B. Chem. Heterocycl. Compd. (Engl. Transl.) 1976, 12, 607. (c) Beilstein; 233, 487.
2. Screttas, G. C.; Eastham, J. F. JACS 1965, 87, 3276.
3. Drewes, S. E.; Roos, G. H. P. T 1988, 44, 4653.
4. Kaiser, E. M.; Warner, C. D. S 1975, 395.
5. Huang, S-B.; Parish, E. J.; Miles, D. H. JOC 1974, 39, 2647.
6. Ho, T.-L. S 1972, 702.
7. Philips, J. C.; Swisher, J. V.; Haidukewych, D.; Morales, O. CC 1971, 22.
8. Komatsu, M.; Ichijima, S.: Ohshiro, Y.; Agawa, T. JOC 1973, 38, 4341.
9. Hoffmann, H. M. R.; Ismail, Z. M.; Hollweg, R.; Zein, A. R. BCJ 1990, 63, 1807.
10. Hubbard, J. L.; Fuller, J. C.; Jackson, T. C.; Singaram, B. T 1993, 49, 8311.
11. (a) Ovannes, C.; Wilson, T. JACS 1968, 90, 6527. (b) Clennan, E. L.; Noe, L. J.; Wen, T.; Szneler, E. JOC 1989, 54, 3581.
12. (a) Hartshorn, S. R.; Thind, S. S. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R.; Rees, C. W., Eds; Pergamon: Oxford, 1984; Vol. 1, p 405. (b) Nakamura, H.; Takata, T.; Endo, T. Macromolecules 1990, 23, 3032.
13. (a) Liu, H. J.; Oppong, I. V. CJC 1982, 60, 94. (b) Liu, H.-J.; Ho, L.-K.; Lai, H. K. CJC 1981, 59, 1685.
14. Mallan, J. M.; Bebb, R. L. CRV 1969, 69, 693.
15. Corey, E. J.; Jautelat, M. TL 1968, 5787.
16. Robertson, D. W.; Katzenllenbogen, J. A. JMC 1982, 25, 167.
17. Baylis, A. B.; Hillman, M. E. D. Ger. Patent 2 155 113, 1972 (CA 1972, 77, 34 174q).
18. Fort, Y.; Berthe, M. C.; Caubere, P. T 1992, 48, 6371.
19. Van Rozendaal, E. L. M.; Voss, B. M. W.; Scheermen, H. W. T 1993, 49, 6931.
20. Ameer, F.; Drewes, S. E.; Freese, S.; Kaye, P. T. SC 1988, 18, 495.
21. Kundu, M. K.; Mukherjee, S. B.; Balu, N.; Padmakumar, R.; Bhat, S. V. SL 1994, 444.
22. Basavaiah, D.; Pandiaraju, S.; Sarma, P. K. S. TL 1994, 35, 4227.
23. Drewes, S. E.; Manickum, T.; Roos, G. H. P. SC 1988, 18, 1065.
24. Manickum, T.; Roos, G. SC 1991, 21, 2269.
25. (a) Kundig, E. P.; Xu, L.-H.; Romanens, P.; Bernardinelli, G. TL 1993, 34, 7049. (b) Kundig, E. P.; Xu, L.-H.; Schnell, B. SL 1994, 413.
26. Gilday, J. P.; Paquette, L. A. OPP 1990, 22, 169.
27. Miles, D. H.; Huang, B.-S. JOC 1976, 41, 208.
28. Waldislaw, B.; Marzorati, L.; Donnici, C. L. JCS(P1) 1993, 3167.
29. Charaf, A.; Otto, H. H. AP 1983, 316, 887.
30. Chenevert, R.; Plante, R.; Voyer, N. SC 1983, 13, 403.
31. Chauvin, C.; Plusquellec, D. TL 1991, 32, 3495.
32. Singaram, B.; Pai, G. G. H 1982, 18, 387.
33. (a) Marinetti, A.; Mathey, F. AG(E) 1988, 27, 1382. (b) Marinetti, A.; Richard, L.; Mathey, F. OM 1990, 9, 788.
34. Blair, K. L.; Baldwin, J.; Smith, Jr. W. C. JOC 1977, 42, 1816.
35. Oae, S.; Ohinishi, Y.; Kozuka, S.; Tagaki, W. BCJ 1966, 39, 364.
36. Cookson, P. G.; Davies, A. G.; Fazal, N. JOM 1975, 99, C31.
37. Taddei, M.; Ricci, A. S 1986, 633.
38. Hwu, J. R. JOC 1983, 48, 4433.

Uppuluri V. Mallavadhani

Regional Research Laboratory, Bhubaneswer, India

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