Facile routes to alkoxymaleimides/maleic anhydrides

Article abstract of DOI:10.1055/s-2003-37351

New routes to alkoxymaleic anhydrides 1a/b have been described in good yields via base-induced chemoselective vinylic substitution of bromo atom in bromomaleimide 4 with alkanols, and base-induced oxa-Micahel addition of alkanols to dialkyl acetylene-dicarboxylates 8a/b as key steps. An unusual acyl exchange in the conversion of 6a/b to 1a/b under very simple and mild reaction conditions is noteworthy.

Full text of DOI:10.1055/s-2003-37351

346
PAPER
Facile Routes to Alkoxymaleimides/Maleic Anhydrides1
A
lkoxymaleimides and
a
A
lkoxym
a
n
leic
A
nhydri
o
des j Kumar Sahoo, Santosh B. Mhaske, Narshinha P. Argade*
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India
Fax +91(20)5893153; E-mail: argade@dalton.ncl.res.in
Received 15 October 2002
Dedicated to Dr. B. G. Hazra, OCS, NCL, Pune.
sis of benzothiazolylacrylic acid.9 The corresponding
methoxymaleimide has been used by Pattenden et al. for
the synthesis of a constituent of the marine blue-green al-
gae pukeleimide A.10 To date two syntheses of methoxy-
Abstract: New routes to alkoxymaleic anhydrides 1a/b have been
described in good yields via base-induced chemoselective vinylic
substitution of bromo atom in bromomaleimide 4 with alkanols, and
base-induced oxa-Micahel addition of alkanols to dialkyl acetylene-
dicarboxylates 8a/b as key steps. An unusual acyl exchange in the maleic anhydride (1a) are known.3,7b,11,12 The first
synthesis11 involves diazomethane-induced methylation
conversion of 6a/b to 1a/b under very simple and mild reaction con-
ditions is noteworthy.
of the enol of ethyl oxaloacetate as a key step. The second
synthesis12 has been completed by using diazomethane for
Key words: bromomaleimide, dialkyl acetylenedicarboxylates,
oxa-Michael additions, alkoxymaleic anhydrides
methylation of the pyridine salt of hydroxymaleic anhy-
drides, which was obtained from tartaric acid in two steps.
Both the above synthesis of 1a use poisonous and explo-
A very large number of applications of cyclic anhydrides sive diazomethane for methylation reactions. Develop-
are known in the literature. Alkoxy, alkoxyalkyl, ment of new, simple, general, and efficient routes to these
alkoxyaryl and dialkoxymaleic anhydrides have been potential building blocks, the cyclic anhydrides is a chal-
used for the synthesis of several bioactive natural prod- lenging task of current interest.13 Very recently we have
ucts.2 Methoxymaleic anhydride [3-methoxyfuran-2,5-di- completed14 a rapid access to alkoxysuccinic acids via
one (1a)] has been used for the synthesis of bioactive oxa-Michael addition of alcohols to alkyl maleanilates,
natural products narthigenine,3 penicillic acid,4,5 and luci- and in continuation of our ongoing programme15 on the
done.6 Highly regioselective Wittig7 reactions and metal synthesis of several natural and unnatural cyclic anhy-
hydride8 reductions have been performed on 1a to obtain drides, we report herein reasoned and planned new routes
precursors of bioactive natural products, the butyrolac- to 1a/b, using alkanols as a source of OR group
tones. The anhydride 1a has been also used for the synthe- (Scheme 1).
Scheme 1 Reagents and conditions: (i) Br2, CCl4, reflux, 1 h (98%); (ii) TEA, THF, 0 °C, 2 h (98%); (iii) Et3N, ROH, reflux, 1 h (70–75%);
(iv) (a) aq KOH, MeOH, r.t., 1 h, (b) H+/HCl (96%); (v) Ac2O–HOAc (1:1), 80 °C, 4 h (95%); (vi) Et3N, ROH, r.t., 2 h (94–96%); (vii) (a) aq
KOH, MeOH, r.t., 6 h, (b) H+/HCl (93–96%); (viii) SOCl2, reflux, 24 h (64–65%)
Synthesis 2003, No. 3, Print: 28 02 03.
Art Id.1437-210X,E;2003,0,03,0346,0349,ftx,en;Z13302SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

PAPER
Alkoxymaleimides and Alkoxymaleic Anhydrides
347
The reaction of N-phenylmaleimide (2) with bromine in In summary, we have demonstrated new general ap-
refluxing CCl4 gave the trans-dibromosuccinimide 3 in proaches to alkoxymaleic anhydrides via base induced vi-
quantitative yield.16 Triethylamine-induced dehydrobro- nylic substitution of bromo atom in 4 with alkanols and
mination of 3 at 0 °C yielded the bromomaleimide 4 in oxa-Michael addition of alkanols to dialkyl acetylenedi-
nearly 98% yield. The chemoselective base-catalyzed vi- carboxylates 8a/b. Such a chemoselective nucleophilic vi-
nylic substitution of bromine atom in imide 4 with meth- nylic substitutions under very simple and mild reaction
anol/ethanol gave the alkoxymaleimides 5a/b in 70–75% conditions will be useful in organic synthesis. The ob-
yields. The reaction of dibromosuccinimide 3 with Et3N– served substrate, reagent and reaction conditions specific
MeOH also gave 5a, but in 20–25% yield only. In our for an unusual acyl exchange reaction is noteworthy.
hands the compounds 5a/b on acid-catalyzed hydrolysis
(HCl, reflux, 1 h) underwent dealkylation reactions and
Melting points are uncorrected. 1H NMR spectra were recorded on
furnished only decomposed/polymeric gums. The base-
Bruker AC 200 NMR spectrometer (200 MHz) with TMS as an in-
induced regioselective hydrolysis of 5a/b at room temper-
ternal standard. Mass spectra were recorded on Finnigan Mat 1020
mass spectrometer at 70 eV. Column chromatographic separations
ature gave the corresponding maleanilic acids 6a/b in
quantitative yields. The cleavage of amide bond in anilic
acids generally demands strong reaction conditions.17 Re-
markably the maleanilic acids 6a/b in 1:1 mixture of ace-
tic anhydride and acetic acid at 80 °C underwent a smooth
acyl exchange reaction and furnished the mixture of acet-
anilide and desired alkoxymaleic anhydrides 1a/b in 95%
yield. We feel that, the present observed acyl exchange re-
action is substrate, reagent and reaction conditions specif-
were done on ACME silica gel (60–120 mesh). Petroleum ether
with a bp range of 60–80 °C was used. Dimethyl acetylenedicarbox-
ylate and diethyl acetylenedicarboxylate were obtained from Ald-
rich Chemical Co. N-Phenylmaleimide (2) was prepared in
quantitative yield using known procedure.20
trans-2,3-Dibromo-N-phenylsuccinimide (3)
To a solution of N-phenylmaleimide (2; 1.73 g, 10 mmol) in CCl4
(15 mL) was added dropwise a solution of Br2 (0.57 mL, 11 mmol)
ic. The free carboxyl group, carbon–carbon double bond in CCl4 (10 mL) at r.t. After complete addition, the reaction mixture
was refluxed for 1 h, and then allowed to cool to r.t. The precipitate
was filtered and washed with CCl4 (2 × 5 mL) and dried; yield: 3.26
g (98%); mp 155–157 °C.
IR (Nujol): 1798, 1728, 1591 cm−1.
1H NMR (CDCl3, 200 MHz): δ = 4.87 (s, 2 H), 7.30–7.70 (m, 5 H).
13C NMR (CDCl3, 50 MHz): δ = 41.9, 44.4, 126.0, 129.4, 130.8,
with cis geometry and acetic anhydride/acetic acid combi-
nation is necessary for the above acyl exchange reaction.
We also feel that the present exchange reaction is plausi-
bly taking place via the intermediate acyclic imides 7a/b.
In our second approach we studied the base-induced oxa-
Michael addition of alcohols to 8a/b to obtain exclusively
or in major amounts, the E-isomers of the dialkyl alkoxy-
130.9, 169.2, 169.5.
maleates 9a/b.18 All our attempts using different tempera- MS: m/z = 335, 333, 331, 253, 251, 196, 173, 144, 128, 119, 104,
91, 77.
tures and bases met with failure and we always got the
10a/b as major products. The best yield of 9a/b plus 10a/
b (94–96%) was obtained from the reaction of 8a/b and
alkanols using triethylamine as a base at room tempera-
ture in 2 hours (9a:10a = 30:70 and 9b:10b = 20:80, by
1H NMR spectroscopy). We could very easily separate
these E- and Z-isomers 9a/b and 10a/b by silica gel col-
umn chromatography for characterization. Potassium hy-
droxide-catalyzed hydrolysis of E- and Z-mixture of ester
9a/b and 10a/b followed by acidification gave the corre-
sponding mixture of acids 11a/b and 12a/b in 93–96%
yields with same E:Z ratio. The pure esters 9a/b and 10a/
b were also similarly hydrolyzed to corresponding acids
11a/b and 12a/b respectively. The mixture of acids 11a
plus 12a and 11b plus 12b in refluxing thionyl chloride re-
spectively furnished the desired alkoxymaleic anhydrides
1a and 1b in 64–65% yield. Both isomerization of Z-iso-
mers 12a/b to E-isomers 11a/b and dehydrative ring-clo-
sure took place in one-pot.6 The analytical and spectral
data obtained for 1a/b were in complete agreement with
reported data.11,12 The overall yield of 1a/b in five steps (2
to 1a/b) and three steps (8a/b to 1a/b) were 61–66% and
56–60% respectively. The one-step conversion of meth-
oxymaleic anhydride (1a) to bioactive natural products
narthigenine (antibiotic)3 and penicillic acid (antimicrobi-
al, antitumor, blood vessels dilation, antidiuretic)4,19 are
known.
Anal. Calcd for C10H7Br2NO2: C, 36.07; H, 2.12; N, 4.21. Found: C,
35.84; H, 2.19; N, 4.35.
2-Bromo-N-phenylmaleimide (4)
To a solution of 3 (3.0 g, 9 mmol) in THF (30 mL) was added drop-
wise a solution of Et3N (1.38 mL, 9.9 mmol) in THF (5 mL) at 0 °C
and the mixture was stirred for 2 h. The mixture was allowed to
warm to r.t. and concentrated in vacuo. The residue was dissolved
in EtOAc and washed with H2O, brine and dried (Na2SO4). Concen-
tration of the organic layer in vacuo furnished 4; yield: 2.23 g
(98%); mp 161–163 °C.
IR (Nujol): 1782, 1716, 1713, 1595 cm−1.
1H NMR (CDCl3, 200 MHz): δ = 7.03 (s, 1 H), 7.30–7.60 (m, 5 H).
13C NMR (CDCl3, 50 MHz): δ = 126.0, 128.2, 129.1, 131.0, 131.7,
131.8, 164.1, 167.3.
MS: m/z = 253, 251, 211, 196, 171, 144, 128, 119, 104, 91, 77, 71,
64.
Anal. Calcd for C10H6BrNO2: C, 47.65; H, 2.40; N, 5.56. Found: C,
47.71; H, 2.29; N, 5.50.
2-Methoxy-N-phenylmaleimide (5a)
To a solution of 4 (1.0 g, 3.97 mmol) in MeOH (10 mL) was added
a solution of Et3N (0.61 mL, 4.37 mmol) in MeOH (5 mL), and the
reaction mixture was refluxed for 1 h. Concentration of the mixture
in vacuo followed by silica gel column chromatographic purifica-
tion of the residue using petroleum ether–EtOAc (8:2) as eluent
gave 5a; yield: 604 mg (75%); mp 99–101 °C.
IR (Nujol): 1778, 1730, 1715, 1643, 1599 cm−1.
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348
M. K. Sahoo et al.
PAPER
1H NMR (CDCl3, 200 MHz): δ = 4.02 (s, 3 H), 5.58 (s, 1 H), 7.25–
10a
7.55 (m, 5 H).
Yield: 4.17 g (68%); thick oil.
13C NMR (CDCl3, 50 MHz): δ = 58.9, 96.3, 125.9, 127.6, 128.9,
131.0, 160.6, 164.2, 168.8. MS: m/z = 203, 174, 147, 119, 105, 88,
84, 77, 69, 64, 59.
IR (CHCl3): 1745, 1726, 1641, 1437, 1362, 1269 cm−1.
1H NMR (CDCl3, 200 MHz): δ = 3.75 (s, 3 H), 3.84 (s, 3 H), 3.93
(s, 3 H), 6.18 (s, 1 H).
Anal. Calcd for C11H9NO3: C, 65.02; H, 4.46; N, 6.90. Found: C,
65.19; H, 4.67; N, 6.76.
13C NMR (CDCl3, 50 MHz): δ = 51.1, 52.3, 60.5, 107.3, 154.4,
162.7, 164.2.
MS: m/z = 174, 159, 143, 127, 115, 110, 101, 84, 69, 59, 53.
2-Ethoxy-N-phenylmaleimide (5b)
Repetition of above reaction with EtOH furnished 5b; yield: 70%;
mp 116–117 °C.
Anal. Calcd for C7H10O5: C, 48.28; H, 5.79; Found: C, 48.39; H,
5.97.
IR (Nujol): 1782, 1720, 1641, 1605 cm−1.
1H NMR (CDCl3, 200 MHz): δ = 1.54 (t, J = 6 Hz, 3 H), 4.22 (q,
J = 6 Hz, 2 H), 5.53 (s, 1 H), 7.25–7.60 (m, 5 H).
Diethyl Ethoxymaleate/Diethyl Ethoxyfumarate (9b/10b)
Similarly the reaction of 8b with EtOH afforded 9b (18%) and 10b
(76%) in a total of 94% yield.
Anal. Calcd for C12H11NO3: C, 66.35; H, 5.11; N, 6.45. Found: C,
66.47; H, 5.02; N, 6.53.
9b
Yield : 18%; thick oil.
2-Methoxymaleanilic Acid (6a)
IR (CHCl3): 1746, 1713, 1626, 1379, 1194 cm−1.
To a solution of 5a (500 mg, 2.46 mmol) in MeOH (5 mL) was add-
ed a solution of KOH (207 mg, 3.7 mmol) in H2O (5 mL) and the
reaction mixture was stirred for 1 h at r.t. The mixture was concen-
trated in vacuo and acidified with aq 10 N HCl at 0 °C. The precip-
itate formed was filtered and dried under vacuo; yield: 523 mg
(96%); mp 184–185 °C.
1H NMR (CDCl3, 200 MHz): δ = 1.26 (t, J = 6 Hz, 3 H), 1.37 (t,
J = 6 Hz, 3 H), 1.40 (t, J = 6 Hz, 3 H), 3.93 (q, J = 8 Hz, 2 H), 4.16
(q, J = 8 Hz, 2 H), 4.35 (q, J = 8 Hz, 2 H), 5.15 (s, 1 H).
13C NMR (CDCl3, 50 MHz): δ = 13.3, 13.4, 13.7, 59.7, 61.6, 65.5,
92.6, 161.7, 163.3, 165.4.
IR (Nujol): 3265, 1730, 1653, 1612, 1460, 1321 cm−1.
MS: m/z (%) = 216, 201, 187, 171, 143, 115, 99, 87, 69.
1H NMR (methanol-d4, 200 MHz): δ = 3.79 (s, 3 H), 5.75 (s, 1 H),
7.12 (t, J = 8 Hz, 1 H), 7.33 (t, J = 8 Hz, 2 H), 7.57 (d, J = 8 Hz, 2
H).
Anal. Calcd for C10H16O5: C, 55.54; H, 7.46; Found: C, 55.64; H,
7.23.
10b
Anal. Calcd for C11H11NO4: C, 59.72; H, 5.01; N, 6.33. Found: C,
59.61; H, 4.93; N, 6.19.
Yield: 76%; thick oil.
IR (CHCl3): 1736, 1730, 1641, 1634, 1376, 1257 cm−1.
2-Ethoxymaleanilic Acid (6b)
The above reaction carried out in EtOH afforded 6b; yield: 96%; mp
145–147 °C.
IR (Nujol): 3290, 1709, 1616, 1462 cm−1.
1H NMR (methanol-d4, 200 MHz): δ = 1.41 (t, J = 8 Hz, 3 H), 3.97
(q, J = 8 Hz, 2 H), 5.69 (s, 1 H), 7.10 (t, J = 8 Hz, 1 H), 7.31 (t,
J = 8 Hz, 2 H), 7.56 (d, J = 8 Hz, 2 H).
1H NMR (CDCl3, 200 MHz): δ = 1.29 (t, J = 6 Hz, 3 H), 1.33 (t,
J = 6 Hz, 3 H), 1.36 (t, J = 6 Hz, 3 H), 4.10–4.40 (m, 6 H), 6.18 (s,
1 H).
13C NMR (CDCl3, 50 MHz): δ = 13.8, 13.9, 15.1, 60.2, 61.8, 69.3,
109.2, 154.1, 162.8, 164.2.
MS: m/z = 216, 187, 171, 143, 115, 99, 87, 69.
Anal. Calcd for C10H16O5: C, 55.54; H, 7.46; Found: C, 55.41; H,
7.48.
Anal. Calcd for C12H13NO4: C, 61.27; H, 5.57; N, 5.96. Found: C,
61.20; H, 5.69; N, 6.03.
Methoxymaleic Acid (11a)
Dimethyl Methoxymaleate/Dimethyl Methoxyfumarate (9a/
10a)
To a solution of 9a (1.0 g, 5.75 mmol) in MeOH (15 mL) was added
a solution aq 4 N KOH (15 mL) and the reaction mixture was stirred
at r.t. for 6 h. The mixture was cooled to 0 °C and acidified with aq
10 N HCl till pH 2. The aqueous layer was extracted with Et2O
(5 × 20 mL) and the organic layer was washed with H2O, brine and
dried (Na2SO4). Concentration of organic layer in vacuo gave 11a;
yield: 780 mg (93%); mp 128–130 °C.
To a stirred solution of dimethyl acetylenedicarboxylate (8a; 5.0 g,
35.21 mmol) in MeOH (50 mL) was added dropwise Et3N (2.7 mL,
19.37 mmol) and the reaction mixture was stirred at r.t. for 2 h. Con-
centration of the mixture in vacuo followed by column chromato-
graphic purification of the residue by silica gel column
chromatography using petroleum ether–EtOAc (9:1) as eluent gave
9a and 10a in a total yield of 96%.
IR (Nujol): 1701, 1690, 1637, 1215 cm−1.
1H NMR (acetone-d6, 200 MHz): δ = 3.81 (s, 3 H), 5.33 (s, 1 H).
13C NMR (acetone-d6, 50 MHz): δ = 57.4, 93.8, 164.0, 164.2, 168.0.
MS: m/z = 146, 128, 102, 87, 84, 69, 53.
9a
Yield: 1.72 g (28%); thick oil.
IR (CHCl3): 1753, 1720, 1630, 1439, 1371 cm−1.
1H NMR (CDCl3, 200 MHz): δ = 3.71 (s, 3 H), 3.75 (s, 3 H), 3.89
(s, 3 H), 5.21 (s, 1 H).
Anal. Calcd for C5H6O5: C, 41.11; H, 4.14; Found: C, 41.01; H,
4.19.
13C NMR (CDCl3, 50 MHz): δ = 51.1, 52.4, 56.6, 92.7, 162.1,
163.5, 165.8.
Compounds 12a, 11b, and 12b were prepared similarly to 11a. A
mixture of 9a/b and 10a/b were also hydrolyzed to the correspond-
ing mixture of acids.
MS: m/z = 174, 159, 143, 127, 115, 110, 101, 85, 69, 59, 53.
Anal. Calcd for C7H10O5: C, 48.28; H, 5.79; Found: C, 48.35; H,
5.91.
Synthesis 2003, No. 3, 346–349 ISSN 0039-7881 © Thieme Stuttgart · New York

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Alkoxymaleimides and Alkoxymaleic Anhydrides
349
Methoxyfumaric Acid (12a)
Yield: 95%; mp 141–143 °C.
Anal. Calcd for C6H6O4: C, 50.71; H, 4.26; Found: C, 50.82; H,
4.29.
IR (Nujol): 1702, 1692, 1643, 1462, 1279, 1231 cm−1.
1H NMR (acetone-d6, 200 MHz): δ = 3.92 (s, 3 H), 6.17 (s, 1 H).
Acknowledgments
13C NMR (DMSO-d6, 50 MHz): δ = 60.3, 108.7, 154.9, 164.2,
165.7.
M. K. S. and S. B. M. thank CSIR, New Delhi, for the award of a
research fellowship. N. P. A. thanks the Department of Science and
Technology, New Delhi, for financial support. We thank Mr. R.
Senthil Kumar (M. Sc. project student) for few preliminary experi-
ments. We also thank Dr. K. N. Ganesh, Head, Division of Organic
Chemistry (Synthesis) for constant encouragement.
MS: m/z = 146, 128, 110, 98, 87, 69, 59, 53.
Anal. Calcd for C5H6O5: C, 41.11; H, 4.14; Found: C, 41.13; H,
4.19.
Ethoxymaleic Acid (11b)
Yield: 96% yield; mp 120–121 °C.
References
IR (Nujol): 1730, 1685, 1454, 1377 cm−1.
(1) NCL Communication No. 6633.
(2) (a) Pattenden, G. Fortsch. Chem. Org. Naturstoffe 1978, 35,
133. (b) Gaudreault, R. C.; Mongrain, C. PCT Int. Appl. WO
9108775, 1989; Chem. Abstr. 1991, 115, 183069.
(c) Becker, R.; Rohr, W. Eur. Pat. Appl. Ep 289925, 1988;
Chem. Abstr. 1989, 111, 40070.
1H NMR (acetone-d6, 200 MHz): δ = 1.36 (t, J = 8 Hz, 3 H), 4.02
(q, J = 8 Hz, 2 H), 5.28 (s, 1 H), 8.83 (br s, 2 H).
13C NMR (acetone-d6, 50 MHz): δ = 14.2, 66.6, 93.7, 163.6, 164.2,
167.9.
(3) Stachel, H.-D.; Schachtner, J.; Seidel, J. Z. Naturforsch., B:
Chem. Sci. 1996, 51, 409.
(4) Yeh, C.-L.; Colwell, W. T.; DeGraw, J. I. Tetrahedron Lett.
1978, 42, 3987.
MS: m/z = 142, 116, 98, 87, 69, 57, 53.
Anal. Calcd for C6H8O5: C, 45.01; H, 5.03; Found: C, 45.22; H,
5.10.
(5) Stachel, H.-D.; Schachtner, J. Z. Naturforsch., B: Chem. Sci.
1996, 51, 1334.
(6) Clemo, N. G.; Gedge, D. R.; Pattenden, G. J. Chem. Soc.,
Perkin Trans. 1 1981, 1448.
Ethoxyfumaric Acid (12b)
Yield: 96%; mp 117–118 °C.
IR (Nujol): 1722, 1685, 1423, 1269, 1215 cm−1.
1H NMR (acetone-d6, 200 MHz): δ = 1.32 (t, J = 8 Hz, 3 H), 4.22
(q, J = 8 Hz, 2 H), 6.19 (s, 1H), 8.71 (br s, 2 H).
13C NMR (acetone-d6, 50 MHz): δ = 15.2, 69.8, 109.6, 154.9, 164.0,
(7) (a) Kayser, M. M.; Hatt, K. L.; Yu, H.; Hopper, D. L. Can.
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(8) (a) Wel, H. V. D.; Nibbering, N. M. M. Can. J. Chem. 1988,
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165.6.
MS: m/z = 160, 151, 145, 139, 116, 98, 87, 69, 53.
Anal. Calcd for C6H8O5: C, 45.01; H, 5.03; Found: C, 45.13; H,
5.11.
Methoxymaleic Anhydride (1a)
Method A: A mixture of 11a and 12a (3.5 g, 24 mmol) and SOCl2
(50 mL) was stirred at 25 °C for 1 h and then refluxed for 24 h. The
mixture was concentrated in vacuo and Kugelrohr distillation of the
residue gave 1a (1.96 g, 64%).
(11) Ralph, R. K.; Shaw, G.; Naylor, R. N. J. Chem. Soc. 1959,
1169.
Method B: 2-Methoxymaleanilic acid (6a; 300 mg, 1.36 mmol) was
heated at 80 °C in a mixture of HOAc and Ac2O (1:1, 10 mL) for 4
h. Ac2O and HOAc were distilled off in vacuo and the residue was
purified by silica gel column chromatography using petroleum
ether–EtOAc (8:2) as eluent to obtain 1a (165 mg, 95%); mp 152–
155 °C.
(12) (a) Roberts, J. C. J. Chem. Soc. 1952, 3315. (b) Owen, T.
C.; Austin, D. J. J. Org. Chem. 1993, 58, 756.
(13) (a) Adlington, R. M.; Baldwin, J. E.; Cox, R. J.; Pritchard, G.
J. Synlett 2002, 820. (b) Li, J.; Li, G.; Jiang, H.; Chen, M.
Tetrahedron Lett. 2001, 42, 6923; and references 13a,b cited
therein.
IR (CHCl3): 1857, 1776, 1649, 1225 cm−1.
(14) Mhaske, S. B.; Argade, N. P., unpublished results.
(15) (a) Kar, A.; Argade, N. P. Tetrahedron Lett. 2002, 43, 6563.
(b) Kar, A.; Argade, N. P. J. Org. Chem. 2002, 67, 7131.
(c) Mangaleswaran, S.; Argade, N. P. Synthesis 2002, 865;
and references 15a–c cited therein.
(16) Kar, A.; Argade, N. P. Synthesis 2002, 221.
(17) (a) Mangaleswaran, S.; Argade, N. P. J. Chem. Soc., Perkin
Trans. 1 2000, 3290. (b) Mangaleswaran, S.; Argade, N. P.
J. Chem. Soc., Perkin Trans. 1 2001, 1764.
(18) Ratemi, E. S.; Dolence, J. M.; Poulter, C. D.; Vederas, J. C.
J. Org. Chem. 1996, 61, 6296.
(19) The Merck Index; Merck & Co., Inc.: Rahway, 1996, 12th
ed., 1218.
1H NMR (CDCl3, 200 MHz): δ = 4.04 (s, 3 H), 5.78 (s, 1 H).
13C NMR (acetone-d6, 50 MHz): δ = 61.0, 99.8, 161.9, 163.0, 164.4.
Anal. Calcd for C5H4O4: C, 46.89; H, 3.15; Found: C, 47.02; H,
3.18.
Ethoxymaleic Anhydride (1b)
Similarly 11b and 12b and 6b gave 1b; mp 127–128 °C.
IR (CHCl3): 1760, 1730, 1645, 1618, 1443, 1215 cm−1.
1H NMR (CDCl3, 200 MHz): δ = 1.53 (t, J = 8 Hz, 3 H), 4.24 (q,
J = 8 Hz, 2 H), 5.71 (s, 1 H).
13C NMR (acetone-d6, 50 MHz): δ = 14.0, 70.8, 99.6, 161.9, 162.1,
164.6.
(20) Reddy, P. Y.; Kondo, S.; Toru, T.; Ueno, Y. J. Org. Chem.
1997, 62, 2652.
Synthesis 2003, No. 3, 346–349 ISSN 0039-7881 © Thieme Stuttgart · New York