The first isolation of crystalline ethyl bromozincacetate, typical reformatsky reagent: Crystal structure and convenient preparation

Synthesis

Volumn , Issue 3, 2008, Pages 0409-0412

  Miki, Shokyo ^a   Nakamoto, Koji ^a   Kawakami, Jun Ichi ^a   Handa, Syoji ^a   Nuwa, Shigeru ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

Convenient preparation; Ethyl bromozincacetate; Isolation; Reformatsky reagent; Tetrahydrofuran coordinated dimer

Indexed keywords

CONVENIENT PREPARATION; ETHYL BROMOZINCACETATE; REFORMATSKY REAGENT;

CRYSTAL STRUCTURE; DIMERS; STEREOCHEMISTRY; X RAY ANALYSIS; ZINC POWDER METALLURGY;

ORGANIC COMPOUNDS;

CHLOROTRIMETHYLSILANE; ETHYL BROMOZINCACETATE; REAGENT; TETRAHYDROFURAN; UNCLASSIFIED DRUG; ZINC;

ARTICLE; CRYSTAL STRUCTURE; CRYSTALLIZATION; NUCLEAR MAGNETIC RESONANCE; REFORMATSKY REACTION; STEREOCHEMISTRY; X RAY CRYSTALLOGRAPHY;

EID: 39349099792     PISSN: 00397881     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2008-1032023     Document Type: Article

References (23)

1. (a) Furstner, A. Encyclopedia of Reagents for Organic Synthesis, Vol. 4; John Wiley & Sons: New York, 1995, 2402.
2. (b) Lombardo, M.; Trombini, C. The Chemistry of Organozinc Reagents; Marek, I.; Rappoport, Z., Eds.; John Wiley & Sons: Chichester, 2006, 797.
3. (a) Dekker, J.; Boersma, J.; Gerrit, J. M. van der Kerk J. Chem. Soc., Chem. Commun. 1983, 553.
4. (b) Dekker, J.; Budzelaar, P. H. M.; Boersma, J.; Gerrit, J. M. van der Kerk Organometallics 1984, 3, 1403.
5. In the strongly coordinating solvent DMSO, the reagent was interpreted to be monomeric.
6. Both Orsini et al. (ref. 12) and Dekker et al. (ref. 2) clearly described that they failed to obtain the crystals of this reagent.
7. Bachmann, W. E.; Cole, W.; Wilds, A. L. J. Am. Chem. Soc. 1940, 62, 824.
8. 2O was used as solvent.
9. 2O, sometimes there was 'an induction period' and heating was needed for reaction to be initiated: Zitsman, J.; Johnson, P. Y. Tetrahedron Lett. 1971, 12, 4201.
10. Metallic zinc ca. 96-97% (impurities: Pb, Cd, Fe), particle size 6 μm (average), Honjo Chemical Corporation.
11. ad = 81°C.
12. Figure 4 shows the influence of the addition period of ethyl bromoacetate on the exothermic behavior of the reaction mixture. Fundamentally, the appropriate addition rate varies depending on the reaction scale, cooling capacity, stirring efficiency, etc., and, therefore, should be carefully determined on the basis of suitable safety evaluations.
13. Although we attempted to analyze impurities by an NMR study of the concentrated residue of the obtained ethyl bromozincacetate-THF solution, useful information could not be obtained due to residual THF and other complicated constituents; there was no trace of side products such as ethyl acetoacetate in the NMR spectrum of the isolated crystals. On the other hand, we observed molecular ion peaks of ethyl acetoacetate, diethyl succinate, and other unknown compounds in the GC-MS of the hydrolytically quenched THF soln; adequate GC methods for quantitative analysis of the reagent solution could not be set up.
14. Orsini et al. reported that the ethyl bromozincacetate in THF that they prepared, was contaminated by ethyl acetoacetate; Orsini, F.; Pelizzoni, F.; Ricca, G. Tetrahedron Lett. 1982, 23, 3945.
15. The ethyl derivative was rotationally symmetric, while the tert-butyl derivative was point symmetric.
16. We have been concerned that the reactivity of the reagent itself, not its reactivity in slurry state, was inhibited by irreversible changes during crystallization. However, there were no problems with this crystalline reagent.
17. Kawakami, J.; Nakamoto, K.; Nuwa, S.; Handa, S.; Miki, S. Tetrahedron Lett. 2006, 47, 1201.
18. Even when these solutions were concentrated, crystallization did not occur. On the other hand, the crystallization could not be prevented when DME or another solvent was added after preparing the reagent as the THF solution.
19. We have submitted an international patent application on the present work: Kawakami, J.; Nakamoto, K.; Nuwa, S.; Handa, S.; Miki, S. WO 2003059889, 2003.
20. The crystallographic data have been deposited at the Cambridge Crystallographic Data Center; deposition number CCDC 656586.
21. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, M.; Giacovazzo, C.; Guagliardi, A.; Polidori, G. J. Appl. Crystogr. 1994, 27, 435.
22. Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.; de Gelder, R.; Israel, R.; Smits, J. M. M. The DIRDIF-94 program system, Technical Report of the Crystallography Laboratory; University of Nijmegen: The Netherlands, 1994.
23. Sheldrick, G. M. SHELXL-97, University of Göttingen: Germany, 1997.