Acetaldehyde 3-Bromopropyl Ethyl Acetal

[34399-67-2]  · C7H15BrO2  · Acetaldehyde 3-Bromopropyl Ethyl Acetal  · (MW 211.1)

(electrophilic or nucleophilic hydroxypropylation reagent1)

Alternate Name: 1-bromo-3-(1-ethoxyethoxy)propane.

Physical Data: colorless liquid, bp 49-51 °C/1 mmHg.1

Solubility: sol common organic solvents (i.e. diethyl ether, THF, 1,3-propanediol).

Analysis of Reagent Purity: 1H NMR.

Preparative Method: the reagent has been prepared from 3-bromo-1-propanol and Ethyl Vinyl Ether using dichloroacetic acid as the catalyst.1 The choice of the catalyst was reported to be crucial to the success of the procedure. This preparation provided the product in 92% yield.

Purification: purification was performed by vacuum distillation, bp 49-51 °C/1 mmHg.1

Handling, Storage, and Precautions: the reagent is acid sensitive and is stored at -30 °C over powdered sodium carbonate.1 This is an alkylation reagent; proper protective equipment should be worn and use restricted to a fume hood.

Introduction.

Acetaldehyde 3-bromopropyl ethyl acetal (1) has been utilized as an electrophilic 3-bromo-1-propanol equivalent and as a source of a nucleophilic three-carbon hydroxypropyl synthon.

Nucleophilic Addition.

1-Lithio-3-(1-ethoxyethoxy)propane, prepared from (1) and Lithium in diethyl ether, has been added to aldehydes,2 ketones (eq 1),1,3 lactones (eq 2),4 lactams,5 and chlorosilanes.6 Although the THP ether has also been utilized, the ethoxyethyl ether is hydrolyzed under milder conditions.7 The corresponding organocopper reagent has been added to a,b-unsaturated ketones and alkyl halides.8,9

The Grignard reagent prepared from (1) has been added to b-alkoxy enones (eq 3) and coupled with allylic bromides.10-12

Alkylation.

Carbanions derived from N,N-dimethylhydrazones have been alkylated with (1) (eq 4).13,14 The hydrolysis conditions utilized to regenerate the ketone do not allow for the isolation of the protected alcohol product. This can be overcome with the THP ether.14 Multifunctionalized ethers have also been synthesized using (1).15


1. Eaton, P. E.; Cooper, G. F.; Johnson, R. C.; Mueller, R. H. JOC 1972, 37, 1947.
2. Sansbury, F. H.; Warren, S. TL 1991, 32, 3425.
3. Hasel, W.; Hoffmann, H. M. R. CB 1988, 121, 1461.
4. Jacobson, R.; Taylor, R. J.; Williams, H. J.; Smith, L. R. JOC 1982, 47, 3140.
5. Seeman, J. I.; Chavdarian, C. G.; Secor, H. V.; Osdene, T. S. JOC 1986, 51, 1548.
6. Hudrlik, P. F.; Abdallah, Y. M.; Hudrlik, A. M. TL 1992, 33, 6743.
7. Schreiber, S. L.; Liew, W.-F. JACS 1985, 107, 2980.
8. Eaton, P. E.; Mueller, R. H. JACS 1972, 94, 1014.
9. Anderson, R. J.; Henrick, C. A. JACS 1975, 97, 4327.
10. Becker, D.; Harel, Z.; Nagler, M.; Gillon, A. JOC 1982, 47, 3297.
11. Sha, C. K.; Ouyang, S. L.; Hsieh, D. Y.; Chang, R. C.; Chang, S. C. JOC 1986, 51, 1490.
12. Shea, K. J.; Wise, S.; Burke, L. D.; Davis, P. D.; Gilman, J. W.; Greeley, A. C. JACS 1982, 104, 5708.
13. Schreiber, S. L.; Wang, Z. JACS 1985, 107, 5303.
14. Hudrlik, P. F.; Hudrlik, A. M.; Yimenu, T.; Waugh, M. A.; Nagendrappa, G. T 1988, 44, 3791.
15. Newman, M. S.; Barbee, T. G., Jr.; Blakesley, C. N.; Zia-ud-Din; Gromelski, S., Jr.; Khanna, V. K.; Lee, L.-F.; Radhakrishnan, J.; Robey, R. L.; Sankaran, V.; Sankarappa, S. K.; Springer, J. M. JOC 1975, 40, 2863.

Heinrich J. Schostarez

Upjohn Laboratories, Kalamazoo, MI, USA



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