P r ep a r a tion of â-Keto Ester s a n d â-Dik eton es by C-Acyla tion /
Dea cetyla tion of Acetoa cetic Ester s a n d Aceton yl Keton es w ith
1-Acylben zotr ia zoles
Alan R. Katritzky,* Zuoquan Wang, Mingyi Wang, Chavon R. Wilkerson, C. Dennis Hall, and
Novruz G. Akhmedov
Center for Heterocyclic Compounds, University of Florida, Department of Chemistry,
Gainesville, Florida 32611-7200
katritzky@chem.ufl.edu
Received April 29, 2004
Acyl-, aroyl-, and heteroaroyl-acetic esters 6a -f and 8a -l are prepared by reactions of 1-acylbenzo-
triazoles 1a -k with acetoacetic esters 5 or 7a ,b in the presence of sodium hydride followed by
regioselective deacetylation. Similar C-acylation/deacetylation of acetylacetone and benzoylacetone
affords â-diketones 10a -d and 13a -c, respectively.
SCHEME 1
In tr od u ction
â-Keto esters and â-diketones have been important
intermediates in organic synthesis since the discovery of
the Claisen condensation more than a century ago.1a-i
Familiar general syntheses of â-diketones and â-keto
esters include (i) acylation of ketones or carboxylic esters
by acyl halides or esters2a-d and (ii) acylation of acety-
lacetone or ethyl acetoacetate and their substituted
derivatives by acyl halides or esters followed by base-
promoted cleavage of a carbonyl group.3a-c The above
methods offer many useful synthetic procedures, but
some acyl halides, such as 3-phenyl-2-propynoyl chloride
and 2-pyridoyl chloride, are quite tedious to synthesize,
store, and handle and therefore are often prepared in
situ. Moreover, â-keto ester and â-diketone anions are
ambident; thus, when acetylacetone or ethyl acetoacetate
are reacted with electrophiles such as acyl chlorides in
the presence of base, both C- and/or O-acylation can
occur. For example, under phase-transfer conditions,
acylation of acetylacetone and of ethyl acetoacetate with
acetyl chloride and benzoyl chloride yielded O-acylated
enol esters in 83-98% yields.4a-c The nature of the
solvent, electrophile, metal counterion, reaction temper-
ature, and structure of the substrate influence the
chemoselectivity of such acylations.5
Benzotriazole is a good leaving group and has been
used extensively as a novel synthetic auxiliary.6a-c Gen-
erally, 1-acylbenzotriazoles 1 are more stable than acid
chlorides and can be used in many N-,7a-d C-,8a-c and
O-acylation reactions9a,b (Scheme 1).
We now show that C-acylations of acetoacetic esters
by 1-acylbenzotriazoles, followed by spontaneous deacety-
lation, lead to useful preparative methods for acyl-, aroyl-,
(4) (a) March, J . March’s Advanced Organic Chemistry, 3rd ed.; J ohn
Wiley & Sons: New York, 1985; pp 436-436. (b) J ones, R. A.; Nokkeo,
S.; Singh, S. Synth. Commun. 1977, 7, 195-199. (c) Taylor, E. C.;
Hawks, G. H., III; Mckillop, A. J . Am. Chem. Soc. 1968, 90, 2421-
2422.
(5) Black, T. H. Org. Prep. Proced. Int. 1989, 21, 179-217.
(6) (a) Katritzky, A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron
1991, 47, 2683-2732. (b) Katritzky, A. R.; Lan, X.; Yang, J . Z.; Denisko,
O. V. Chem. Rev. 1998, 98, 409-548. (c) Katritzky, A. R.; Lan, X.; Fan,
W.-Q. Synthesis 1994, 445-456.
(7) (a) Katritzky, A. R.; Levell, J . R.; Pleynet D. P. M. Synthesis 1998,
153-156. (b) Katritzky, A. R.; He, H.-Y.; Suzuki, K. J . Org. Chem. 2000,
65, 8210-8213. (c) Katritzky, A. R.; Wang, M.; Yang, H.; Zhang, S.;
Akhmedov, N. G. Arkivoc 2002, viii, 134-142. (d) Katritzky, A. R.;
Rogovoy, B. V.; Kirichenko, N.; Vvedensky, V. Bioorg. Med. Chem. Lett.
2002, 12, 1809-1811.
(8) (a) Katritzky, A. R.; Pastor, A.; J . Org. Chem. 2000, 65, 3679-
3682. (b) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J . Org.
Chem. 2003, 68, 1443-1446. (c) Katritzky, A. R.; Abdel-Fattah, A. A.
A.; Wang, M. J . Org. Chem. 2003, 68, 4932-4934.
(9) (a) Katritzky, A. R.; Pastor, A.; Voronkov, M. V. J . Heterocycl.
Chem. 1999, 36, 777-781. (b) Wedler, C.; Kleiner, K.; Kunath, A.;
Schick, H. Liebigs Ann. 1996, 881-885.
* Corresponding author.
(1) (a) Claisen, L.; Lowman, O. Ber. Dtsch. Chem. Ges. 1887, 20,
651-654. (b) Claisen, L. Liebigs Ann. Chem. 1896, 291, 100-111. (c)
Yoshida, M.; Fujikawa, K.; Sato, S.; Hara, S. Arkivoc 2003, vi, 36-42.
(d) Cristau, H.-J .; Marat, X.; Vors, J .-P.; Pirat, J .-L. Tetrahedron Lett.
2003, 44, 3179-3181. (e) Christoffers J .; Oertling, H.; Fisher, P.; Frey,
W. Tetrahedron 2003, 59, 3769-2778. (f) Kotha, S.; Manivannan, E.
Arkivoc 2003, iii, 67-76. (g) Kollenz, G.; Dalvi, T. S.; Kappe, C. O.;
Wentrup, C. Arkivoc 2000, 1 (1), 74-79. (h) Katritzky, A. R.; Silina,
A.; Tymoshenko, D. O.; Qiu, G.; Nair, S. K.; Steel, P. J . Arkivoc 2001,
vii, 138-144. (i) Falsone, F. S.; Kappe, C. O. Arkivoc 2001, ii, 122-
134.
(2) (a) Movchan, T. I.; Voloshanovskii, I. S. J . Appl. Chem. USSR
(Engl. Transl.) 1992, 65, 1973-1976. (b) Linn, B. O.; Hauser, C. R. J .
Am. Chem. Soc. 1956, 78, 6066-6070. (c) Hauser, C. R.; Hudson, B.
E., J r. In Org. React.; Adams, R., Bachmann, W. E., J ohnson, J . R.,
Fieser, L. F., Snyder, H. R., Eds.; J ohn Wiley & Sons: New York, 1942;
Vol. 1, pp 266-289. (d) Casey, M.; Donnelly, J . A.; Ryan, J . C.; Ushioda,
S. Arkivoc 2003, vii, 310-327.
(3) (a) Berend, L.; Heymann, F. J . Prakt. Chem. 1902, 290-294. (b)
Duff, J . C. J . Chem. Soc. 1914, 105, 2182-2186. (c) McElvain, S. M.;
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10.1021/jo049274l CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/26/2004
J . Org. Chem. 2004, 69, 6617-6622
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