Notes
J . Org. Chem., Vol. 62, No. 14, 1997 4863
CH2), 32.0, 37.5, 126.2 (2-carbons, see proton-coupled 13C NMR
data), 129.6, 130.8, 138.2, 140.3, 168.7, 177.2; the signals for
the C-4 methyl carbon, the C-4 carbon, and the proton bearing
olefinic carbon from the corresponding (Z)-isomer appeared at
δ 16.2, 39.5, and 144.1, respectively; proton-coupled 13C NMR
(CDCl3, 50 MHz) δ 13.8-38.0 (complex pattern, proton bearing
saturated carbons), 126.3 (d), 126.4 (s), 129.8 (d), 130.8 (s), 138.4
(s), 140.6 (d), 168.9 (s), 177.4 (s); MS (m/e) 397, 242, 229, 216,
203, 133, 118, 107, 95, 91, 81, 67, 55; IR (CHCl3) νmax 1705, 1665
sively the mixture of 7 plus 8 in 71% yield (E:Z ) 85:15,
1
by integration of vinylic proton in H NMR) via 6. When
the acetic acid was distilled off under normal atmospheric
pressure at 140-150 °C bath temperature, and the oily
residue was further heated at the same temperature for
the next 30 min, the above reaction directly gave male-
imide derivative 9 via 6 and 7 plus 8 in 91% yield, thus
offering both condensation and the isomerization of
double bond (exo to endo) in one pot. The mixture of 7
plus 8 on treatment with sodium methoxide in methanol
under reflux conditions followed by acidification directly
gave cheatomellic acid A anhydride (1) in 62% yield. The
disubstituted maleimide 9 on alkaline hydrolysis under
reflux conditions in a THF-methanol-water mixture as
the solvent system followed by acidification gave 1 in 98%
yield, thus providing 1 in two steps (4 f 9 f 1) with
89% overall yield. It is known1 that 1 in basic medium
stays in the biologically active dianionic form 2.
In summary, we have demonstrated for the first time
that the citraconimide-TPP adduct 6 condenses with
aliphatic aldehyde (tetradecanal), providing a facile two-
step synthesis of chaetomellic acid A anhydride (1) with
89% overall yield and access to analogues of 1, hence a
new convenient and efficient method to model a variety
of other dialkyl-substituted maleic anhydride derivatives.
cm-1
. Anal. Calcd for C26H39NO2: C, 78.54; H, 9.89. Found:
C, 78.67; H, 9.96.
Similarly the adduct 6 with tetradecanal under the same set
of conditions gave a mixture of 7 plus 8 in 70-75% yield.
N-p-Tolylch a etom ellic Acid A Im id e (9). The imide 9 was
prepared using the same procedure as described for the prepara-
tion of 7 plus 8, except that the acetic acid was distilled off slowly
over a period of 15 min at 140-150 °C bath temperature and
the oily residue was further heated with stirring for 30 min at
same bath temperature. 9: 720 mg (91% yield); mp 74-76 °C;
1H NMR (CDCl3, 200 Hz) δ 0.90 (t, J ) 7 Hz, 3H), 1.30 (bs, 22H),
1.60 (m, 2H), 2.06 (s, 3H), 2.38 (s, 3H), 2.47 (t, J ) 7 Hz, 2H),
7.24 (bs, 4H); 13C NMR (CDCl3, 50 MHz) δ 9.0, 14.3, 21.3, 22.9,
24.0, 28.4, 29.5-29.9 (9 × CH2), 32.1, 125.9 (2-carbons), 129.8,
137.3, 137.4, 141.5, 171.0, 171.3; MS (m/e) 397, 382, 294, 228,
215, 203, 183, 149, 107, 91, 81, 67, 57; IR (Nujol) νmax 1710, 1690,
1650 cm-1
. Anal. Calcd for C26H39NO2: C, 78.54; H, 9.89.
Found: C, 78.72; H 9.77.
Similarly the adduct 6 with tetradecanal under the same set
of conditions gave imide 9 in 88-90% yield.
Ch a etom ellic Acid A An h yd r id e (1). (a ) A mixture of 7
plus 8 (100 mg) in a solution of sodium methoxide (100 mg) in
methanol (5 mL) was refluxed for 2 h with stirring. The
methanol was removed in vacuo. The residue was acidified with
dilute HCl and ether extracted (10 mL × 2), and the organic
layer was washed with water and brine and dried over Na2SO4.
Concentration in vacuo followed by silica gel column chromato-
graphic purification of the residue furnished pure 1 (thick oil):
48 mg (62% yield). (b) To the solution of imide 9 (100 mg) in a
THF-methanol mixture (6 mL, THF:MeOH ) 1:2) was added
a solution of KOH (300 mg) in water (1 mL), and the reaction
mixture was refluxed for 2 h with stirring. The solvent mixture
was removed in vacuo, and the residue was acidified with dilute
HCl. Repetition of the above workup procedure followed by silica
gel column chromatographic purification furnished pure 1: 76
mg (98% yield); 1H NMR (CDCl3, 200 MHz) δ 0.88 (t, J ) 7 Hz,
3H), 1.15-1.45 (bs, 22H), 1.56 (m, 2H), 2.07 (s, 3H), 2.45 (t, J )
7 Hz, 2H); 13C NMR (CDCl3, 50 MHz) δ 9.6, 14.3, 22.9, 24.6,
27.7, 29.0-31.0 (9 × CH2), 32.1, 140.6, 144.9, 166.0, 166.4; MS
(m/e) 308, 290, 206, 191, 168, 150, 136, 126, 115, 105, 95, 91,
Exp er im en ta l Section
Melting points are uncorrected. Column chromatographic
separations were done on ACME silica gel (60-120 mesh).
Triphenylphosphine, citraconic anhydride, and tetradecanal
were obtained from Aldrich. The citraconimide 4 was obtained18
in quantitative yield from citraconic anhydride (3) via dehydra-
tion of mixture of corresponding regioisomers of maleanilic acids.
Met h yl(t r ip h en ylp h osp h or a n ylid en e)su ccin ic An h y-
d r id e (5) a n d Met h yl-N-p -t olyl(t r ip h en ylp h osp h or a n yl-
id en e)su ccin im id e (6). These were prepared using literature
1
procedures.8 5: mp 180-181 °C; H NMR (CDCl3, 90 MHz) δ
0.82 (d, J ) 7 Hz, 3H), 3.36 (q, J ) 8 Hz, 1H), 7.30-7.80 (m,
15H). 6: mp 98-102 °C; 1H NMR (CDCl3 + DMSO-d6, 200
MHz) δ 1.15 (d, J ) 7 Hz, 3H), 3.10 (s, 3H), 3.85-4.20 (m, 1H),
7.30-7.80 (m, 19H).
3-(E /Z)-Te t r a d e cylid e n e -4-m e t h yl-N-p -t olylsu ccin im -
id es (7/8). A mixture of citraconimide 4 (402 mg, 2 mmol),
triphenylphosphine (524 mg, 2 mmol), and tetradecanal (636 mg,
3 mmol, 80% purity) in glacial acetic acid (10 mL) was refluxed
with stirring for 18 h. Acetic acid was distilled off in vacuo at
50 °C, and the residue was dissolved in ethyl acetate (25 mL).
The organic layer was washed with water and brine and dried
over Na2SO4. Concentration of the organic layer in vacuo
followed by silica gel column chromatographic purification of the
residue using a mixture of petroleum ether and ethyl acetate
81, 69; IR (neat) νmax 2960, 2940, 2925, 2860, 1770, 1680 cm-1
.
Anal. Calcd for C19H32O3: C, 73.98; H, 10.46. Found: C, 73.72;
H, 10.39. IR, 1H NMR, 13C NMR, and mass data are in
agreement with literature1 values.
Ack n ow led gm en t. S.B.D. thanks CSIR, New Delhi,
for the award of a research fellowship. We thank Dr.
K. N. Ganesh, Head, Division of Organic Chemistry
(Synthesis), for constant encouragement.
1
(9:1) gave a mixture of 7 plus 8 (7:8 ) 85:15 by H NMR): 560
mg (71% yield); mp 53-57 °C; 1H NMR (CDCl3, 200 MHz) δ 0.9
(t, J ) 8 Hz, 3H), 1.30 (bs, 20H), 1.45-1.60 (m, 2H), 1.53 (d, J
) 10 Hz, 3H), 2.20-2.35 (m, 2H), 2.40 (s, 3H), 3.30-3.55 (m,
1H), 6.25 (dt, J ) 4 and 10 Hz, 0.15H), 6.93 (dt, J ) 4 and 10
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
1, 4, 7 plus 8, and 9 and 13C NMR and mass spectra of 1, 7
plus 8, and 9 (14 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
Hz, 0.85H), 7.20 (d, J ) 13 Hz, 2H), 7.30 (d, J ) 13 Hz, 2H); 13
C
NMR (CDCl3, 50 MHz) δ 14.1, 16.4, 21.6, 22.7, 28.4-29.7 (10 ×
(18) Balasubramaniyan. V.; Argade, N. P. Tetrahedron 1989, 45,
835.
J O9700383