ConVersion of â-Ketoesters and â-Diketones to Carboxylic Acids
TABLE 3. Functional Group Compatibility Studiesb
necessary to initiate oxidation, alternative approaches to this
reaction may be possible by initiating the oxidation of â-dicar-
bonyls electrochemically in the presence of nitrate salts.39
Further examination of the mechanistic details of the conversion
are being explored to determine if this mild procedure can be
utilized in other important functional group conversions or bond
forming reactions.
Experimental Section
Materials and Experimental Procedures. All solvents were
4
0
distilled before use. Ceric tetra-n-butylammonium nitrate (CTAN)
and cerium triflate (CTF)41 were prepared following reported
procedures. â-Dicarbonyl substrates 2, 3, 5, 7, 8, 9, 10, 13, 15, 17,
18, 19, 20, 21, 22, and 23 were prepared by the reaction of 2,4-
pentanedione or methyl acetoacetate with corresponding halides
under the treatment of NaH and BuLi. Compound 16 was prepared
from 1-phenylbutane-1,3-dione, methyl iodide, potassium carbonate,
and tetra-n-butylammonium bromide in toluene according to the
published procedure.42 All other substrates were purchased and used
1
13
without further purification. H and C NMR spectra were recorded
on a 500 MHz spectrometer. Infrared experiments were performed
on a React IR system.
Procedure for Oxidation of â-Dicarbonyls with CAN in
CH CN. Ceric ammonium nitrate (CAN, 4.4 mmol, in 10 mL CH -
3 3
CN) solution was added to a solution of the â-dicarbonyl (2 mmol)
in 40 mL of CH CN under N over a period of 2 min. After 4 h,
CH CN was removed at 30 °C by rotary evaporation. Water (75
mL) was poured into the reaction funnel and extracted with 4 ×
5 mL of diethyl ether. The organic extracts were washed with
brine, dried over anhydrous MgSO , filtered, and concentrated via
3
2
3
2
4
rotary evaporation. The residue was analyzed by GC-MS and
purified with column chromatography, using silica gel as the
a
Isolated yield. b Reaction conditions: See footnote b in Table 2.
stationary phase.
Optimized Procedure for Oxidation of â-Dicarbonyls with
experiment can also be formed by reaction of CAN with anisole
alone (albeit at a slower rate).37
CAN in CH CN. Ceric ammonium nitrate (CAN, 4.4 mmol, in 10
3
mL of CH
mmol) in 40 mL of CH
3
CN) was added to a solution of the â-dicarbonyl (2
CN over a period of 2 min under an inert
To be useful in synthesis, it is important to determine the
functional group compatibility for this method. A series of
different â-dicarbonyl substrates containing oxidizable functional
groups were prepared and the results of their reactions with use
of the optimized anhydrous procedure are contained in Table
3
atmosphere. After 4 h, solvent was removed at 30 °C by rotary
evaporation. Ether (40 mL) was poured into the reaction flask and
the solution was dried over anhydrous MgSO , filtered, and
4
concentrated via rotary evaporation. The residue was analyzed by
GC-MS and purified via column chromatography, using silica gel
as the stationary phase.
3. The yields of the reactions are very good and phenyl methoxy
groups, double bonds, alkyl hydroxy groups, and aryliodides
are all compatible with this methodology. Since alcohols and
phenyl methoxy groups are known to be oxidized by CAN, these
findings indicate that the selectivity is likely due to the fast
rate of oxidation of 1,3-dicarbonyls relative to other functional
6
-Naphthalen-2-ylhexane-2,4-dione (3). 6-Naphthalen-2-ylhex-
ane-2,4-dione was prepared by the reaction of 2,4-pentadione and
2-(2-bromoethyl)naphthalene following the general procedure for
the preparation of 2,4-dione derivatives. 3: H NMR (500 MHz,
CDCl
7.2 Hz), 5.49 (s, 1H), 7.30-7.44 (m, 3H), 7.61-7.79 (m, 4H), 15.46
s, 1H). 13C NMR (125 MHz, CDCl
) δ 193.2, 190.4, 138.2, 132.1,
28.1, 127.6, 127.5, 127.0, 126.4, 126.0, 125.3, 100.1, 45.1, 39.9,
1.6, 24.8. MS m/z (rel intensity) 240 (M , 30), 207 (12), 182 (10),
54 (55), 141 (100), 126 (12), 115 (25), 85 (35). HRMS (EI) calcd
for C16
1
3
) δ 2.03 (s, 3H), 2.67 (t, 2H, J ) 7.2 Hz), 2.90 (t, 2H, J )
3
8
groups.
(
3
1
3
1
Conclusions
+
A mild method for the conversion of â-ketoesters and
â-diketones to carboxylic acids with use of CAN in CH3CN
has been developed. The method is compatible with a number
of other functional groups and can be carried out under neutral
conditions. Aside from functional group compatibility, the
procedure can be carried out in a number of solvents as well.
Initial studies of the reaction show that the nitrate ligand is
necessary for the conversion initiated by Ce(IV). Although Ce
is an abundant, nontoxic, and inexpensive metal, one of the
major goals of modern chemical research is to develop chemical
processes that are environmentally benign. If Ce(IV) is only
16 2
H O 240.1150, found 240.1162.
6-(2-Methoxyphenyl)hexane-2,4-dione (17). 6-(2-Methoxyphe-
nyl)hexane-2,4-dione was prepared by the reaction of 2,4-pentadione
and 1-bromomethyl-2-methoxybenzene following the general pro-
cedure for the preparation of 2,4-dione derivatives. 17: H NMR
1
(
500 MHz, CDCl
(t, J ) 8.2 Hz, 2H), 3.53 (s, 0.3H), 3.81 (s, 3H), 5.47 (s, 0.8H),
7.19-7.10 (m, 4H), 15.46 (s, 0.7H). 13C NMR (125 MHz, CDCl
δ 194.0, 191.0, 157.4, 129.8, 129.0, 127.5, 120.4, 110.2, 99.9, 55.2,
3
) δ 2.03 (s, 3H), 2.55 (t, J ) 8.2 Hz, 2H), 2.90
3
)
+
3
8.3, 26.6, 24.9. MS m/z (rel intensity) 220 (M , 35), 134 (33),
(
(
39) Cho, L. Y.; Romero, J. R. Quim. NoVa 1998, 21, 144-145.
40) Muathen, H. A. Ind. J. Chem. 1991, 30B (5), 522-524.
(
37) Dincturk, S.; Ridd, J. H. J. Chem. Soc., Perkin Trans. 2 1982, 961-
64.
38) Zhang, Y.; Flowers, R. A., II J. Org. Chem. 2003, 68, 4560-4562.
(41) Laali, K. K.; Herbert, M.; Cushnyr, B.; Bhatt, A.; Terrano, D. J.
9
Chem. Soc., Perkin Trans. 1 2001, 6, 578-583.
(42) Choudhary, A.; Baumstark, A. L. Synthesis 1989, 9, 688-690.
(
J. Org. Chem, Vol. 71, No. 12, 2006 4519