Nishiwaki et al.
dried over magnesium sulfate and concentrated solvent under
reduced pressure to give crude oil. The residue was treated
with column chromatography on silica gel to give DEOG-
DNP (eluted with benzene-chloroform 1/1, 3.17 g, 8.6 mmol,
86%) as a yellow oil. TLC (SiO2, CHCl3, UV) Rf value ) 0.58;
IR (Nujol/cm-1) 1722, 1701, 1531, 1342; 1H NMR δ ) 1.15 (dd,
J ) 7.1, 7.1 Hz, 3H), 1.27 (dd, J ) 7.1, 7.1 Hz, 3H), 3.11 (d, J
) 15.5 Hz, 1H), 3.23 (d, J ) 15.5 Hz, 1H), 4.0-4.3 (m, 4H),
7.74 (d, J ) 8.4 Hz, 1H), 8.47 (dd, J ) 8.4, 2.3 Hz, 1H), 8.90
(d, J ) 2.3 Hz, 1H), 13.06 (s, 1H); 13C NMR δ ) 13.8 (q), 14.1
(q), 39.5 (t), 61.8 (t), 62.0 (t), 102.5 (s), 120.3 (d), 127.3 (d),
135.2 (d), 135.7 (s), 147.6 (s), 149.5 (s), 167.6 (s), 168.2 (s), 170.0
(s). Anal. Calcd for C15H16N2O9: C, 48.92; H, 4.38; N, 7.61.
Found: C, 49.13; H, 4.37; N, 7.45.
Th e Typ ica l P r oced u r e for th e Tr a n sa cyla tion . To a
solution of EAA-DNP (296 mg, 1 mmol) in chloroform (10
mL), propylamine 5a (82 µL, 1 mmol) was added. The resultant
solution was stirred at room temperature for 1 day. After
removal of the solvent, the residue was treated with column
chromatography on silica gel to afford 7 (eluted with chloro-
form, 233 mg, 0.92 mmol) and N-propylacetamide 6a (eluted
with methanol, 77 mg, 0.95 mmol).
cause for difficulties in the preparation of R-aryl-â-keto
ester compared with R-aryl-â-diketone.
Exp er im en ta l Section
Gen er a l Meth od s. All chemicals were commercially avail-
able and were used as received without further purification.
Tetrahydrofuran (THF) was dried with sodium and distilled
before use. Other solvents were used without drying and
purification. All of the reactions were carried out under
ambient atmosphere. Each transacylated product was isolated
with column chromatography on silica gel (isolated yield was
90-95%), and its structure was determined with comparison
of spectral data with those of authentic sample, which was
commercially available or prepared by acylation of amines (or
alcohols) with commercial acetyl chloride or ethoxymalonyl
1
chloride. The yields of 6 and 9 were determined with H NMR
of the reaction mixture. 1H NMR spectra and 13C NMR spectra
were recorded in CDCl3 at 400 and at 100 MHz, respectively,
with TMS as internal standard. 13C NMR assignments (s, d,
t, and q) were made from DEPT experiments. Column chro-
matography was performed using Merck silica gel 60.
P r ep a r a tion of EAA-DNP . Preparation of EAA-DNP
was conducted by using a procedure modified from the known
method.8 To a solution of EAA-H (1.30 g, 10 mmol) in THF
(10 mL), sodium hydride (60 wt %, 0.80 g, 20 mmol) was
gradually added, and the mixture was stirred at room tem-
perature for 15 min. Then 1-chloro-2,4-dinitrobenzene (DNP -
Cl, 2.02 g, 10 mmol) was added, and the resultant reddish
solution was stirred for 1 day. After addition of 3 M hydro-
chloric acid (10 mL), generated sodium chloride was filtered
off, and the filtrate was concentrated. The extraction of the
residue with hot hexane (30 mL × 3) followed by concentration
afforded EAA-DNP (2.70 g, 9.1 mmol, 91%). Further purifi-
cation was performed with recrystallization from hexane.
EMAA-DNP and AA-DNP were also prepared with the
same procedure.
Eth yl (2,4-Din itr op h en yl)a ceta te. Yellow oil; TLC (SiO2,
CHCl3, UV) Rf value ) 0.40; 1H NMR δ ) 1.27 (t, J ) 7.1 Hz,
3H), 4.16 (s, 2H), 4.19 (q, J ) 7.1 Hz, 2H), 7.62 (d, J ) 8.4 Hz,
1H), 8.45 (dd, J ) 8.4, 2.3 Hz, 1H), 8.95 (d, J ) 2.3 Hz, 1H);
13C NMR δ ) 14.1 (q), 39.7 (t), 61.9 (t), 120.7 (d), 127.5 (d),
134.7 (d), 136.6 (s), 147.4 (s), 148.9 (s), 168.6 (s). In the
transacylation using other amines and alcohols, the experi-
ment was conducted in a similar way.
Rea ction Mon itor ed w ith NMR. To a solution of EAA-
DNP (29.6 mg, 0.1 mmol) in deuterated chloroform (0.3 mL),
propylamine 5a (8.2 µL, 0.1 mmol) was added. The sample tube
1
was allowed to stand at room temperature, and the H NMR
spectrum was measured at intervals of either several minutes
or several hours. Conversion of the reaction was determined
with ratio of integrals for product and starting material since
no signals were observed other than ammonium enolate 8a
and products 6a and 7. When other keto esters and nucleo-
philes were used, the experiments were similarly conducted.
In cases of reactions under heated conditions, the tube was
sealed after the sampling of reagents.
E t h yl
R-(2,4-Din it r op h en yl)-R-m et h yla cet oa cet a t e
(EMAA-DNP ). Yellow plates. Mp 88-89 °C. IR (Nujol/cm-1
)
1722, 1701, 1531, 1342; 1H NMR δ ) 1.17 (dd, J ) 7.2, 7.2
Hz, 3H), 1.98 (s, 3H), 2.59 (s, 3H), 4.12 (dq, J ) 10.7, 7.2 Hz,
1H), 4.21 (dq, J ) 10.7, 7.2 Hz, 1H), 7.70 (d, J ) 8.7 Hz, 1H),
8.50 (dd, J ) 8.7, 2.5 Hz, 1H), 8.99 (d, J ) 2.5 Hz, 1H); 13C
NMR δ ) 13.8 (q), 23.2 (q), 27.8 (q), 62.5 (t), 64.2 (s), 121.1
(d), 127.5 (d), 130.7 (d), 142.0 (s), 147.1 (s), 148.2 (s), 169.7 (s),
203.1 (s). Anal. Calcd for C13H14N2O7: C, 50.33; H, 4.55; N,
9.03. Found: C, 50.63; H, 4.55; N, 9.17.
Com p etition Stu d ies w ith Am in es. To a solution of
EAA-DNP (296 mg, 1 mmol) in chloroform (7 mL) was added
a solution of propylamine 5a (82 µL, 1 mmol) and isopropyl-
amine 5b (85 µL, 1 mmol) in chloroform (3 mL). The resultant
solution was stirred at room temperature for 1 day. After
removal of the solvent, the residue was allowed to measure
P r epar ation of Dieth yl 2-(2,4-Din itr oph en yl)-3-h ydr oxy-
2-p en ten ed ioa te (DEOG-DNP ). To a solution of diethyl
3-oxogulutarate (DEOG-H, 1.82 mL, 10 mmol) and DNP -
Cl (4.05 g, 20 mmol) in ethanol (100 mL) was added triethy-
lamine (14 mL, 100 mmol). The resultant reddish solution was
stirred at room temperature for 7 days. After addition of 1 M
hydrochloric acid (100 mL, 100 mmol), the mixture was
extracted with benzene (50 mL × 3). The organic layer was
1
the H NMR spectrum. As no signal other than 6a , 6b, and 7
was observed, the ratio of transacylated products was deter-
mined with measuring integrals of 6a and 6b. When DEOG-
DNP and other combination of amines were used, experiments
were similarly carried out.
J O0344642
8656 J . Org. Chem., Vol. 68, No. 22, 2003