PAPER
An Efficient Synthesis of Dimethylmaleic Anhydride
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was washed with H2O (15 mL), brine (15 mL) and dried (Na2SO4).
Concentration of organic layer in vacuo followed by column purifi-
cation of the residue (silica gel ; PE–EtOAc, 4:1) gave the mixture
of dimethylmaleimide 7 and N-p-tolyl-2-methylene-3-methylsuc-
cinimide (6) (6:7 = 7:3): 335 mg (31%).
Acknowledgement
S. M. thanks CSIR, New Delhi, for the award of a research fel-
lowship. N. P. A. thanks the Department of Science and Technolo-
gy, New Delhi, for the financial support. We thank Dr. K. N.
Ganesh, Head, Division of Organic Chemistry (Synthesis), for con-
stant encouragement.
1H NMR (CDCl3, 200 MHz): = 1.53 (d, J = 8 Hz, 3 H), 2.40 (s, 3
H), 3.47 (m, 1 H), 5.71 (d, J = 2 Hz, 1 H), 6.47 (d, J = 2 Hz, 1 H),
1
7.10–7.40 (m, 4 H). (The H NMR spectrum of 6 + 7 mixture
showed above signals for 6).
References and Notes
(1) NCL Communication No. 6619.
(2) Gill, B. G.; James, G. D.; Oates, K. V.; Pattenden, G. J.
Chem. Soc., Perkin Trans. 1 1993, 2567.
(3) For references to the use of dimethylmaleic anhydride, see:
Aldrichimica Acta 1980, 13, 53.
(4) (a) Mangaleswaran, S.; Argade, N. P. J. Chem. Soc., Perkin
Trans. 1 2001, 1764. (b) Mangaleswaran, S.; Argade, N. P.
J. Org. Chem. 2001, 66, 5259. (c) Mangaleswaran, S.;
Argade, N. P. J. Chem. Soc., Perkin Trans. 1 2000, 3290.
(d) Desai, S. B.; Argade, N. P. J. Org. Chem. 1997, 62, 4862.
(5) (a) Branchaud, B. P.; Slade, R. M. Tetrahedron Lett. 1994,
35, 4071. (b) Poigny, S.; Guyot, M.; Samadi, M. J. Chem.
Soc., Perkin Trans. 1 1997, 2175. (c) Poigny, S.; Guyot, M.;
Samadi, M. J. Org. Chem. 1998, 63, 1342.
N-p-Tolyldimethylmaleimide (7)
A mixture of N-p-tolylmethylmaleimide (4, 10.24 g, 50.94 mmol),
Ph3P (13.35 g, 50.94 mmol) in glacial HOAc (150 mL) was stirred
at r.t. for 30 min. Paraformaldehyde (7.64 g, 254.7 mmol) was add-
ed to the reaction mixture and then it was refluxed for 2 h. HOAc
was distilled off slowly over a period of 15 min at 50–60 °C bath
temperature and the oily residue was further heated with stirring for
30 min at same bath temperature. Column chromatographic purifi-
cation of the residue (silica gel; PE–EtOAc, 9:1) gave 7: 9.90 g
(91%); mp 109–110 °C.
IR (CHCl3): 1701, 1507, 1388, 1085 cm–1.
1H NMR (CDCl3, 200 MHz): = 2.06 (s, 6 H), 2.38 (s, 3 H), 7.21
(d, J = 8 Hz, 2 H), 7.27 (d, J = 8 Hz, 2 H).
(6) James, G. D.; Pattenden, G.; Mills, S. D. Tetrahedron Lett.
1985, 26, 3617.
(7) Baurain, R. Ger. Offen. 2 756 604, 1978; Chem. Abstr. 1979,
90, 72437d.
(8) Gedge, D. R.; Pattenden, G. J. Chem. Soc., Chem commun
1993, 2567.
(9) (a) Deshpande, A. M.; Natu, A. A.; Argade, N. P. J. Org.
Chem. 1998, 63, 9557; and references cited therein.
(b) Deshpande, A. M.; Natu, A. A.; Argade, N. P. Synthesis
2001, 702.
MS: m/z (%) = 215 (99), 200 (6), 186 (8), 172 (13), 156 (46), 144
(13), 132 (23), 117 (14), 104 (20), 91 (16), 77 (17), 65 (8), 54 (17).
Isomerization of N-p-Tolyl-2-methylene-3-methylsuccinimide
(6) to N-p-Tolyldimethylmaleimide (7)
A mixture of 6 + 7 (100 mg) was heated neat in the oil bath at 50–
60 °C for 3 h. The molten thick oily residue was cooled to r.t. to ob-
tain N-p-tolyldimethylmaleimide (7) in quantitative yield. The exo
compound 6 from 6 + 7 mixture was also completely transformed to
7 at r.t. after 3 days.
(10) (a) Argade, N. P.; Balasubramaniyan, V. Heterocycles 2000,
53, 475. (b) Balasubramaniyan, V.; Argade, N. P.
Tetrahedron 1989, 45, 835.
N-p-Tolyldimethylmaleimide (7); One Pot Synthesis
To a stirred solution of maleimide (1, 3.74 g, 20 mmol) in HOAc (75
mL) was added Ph3P (5.24 g, 20 mmol) and the reaction mixture
was stirred at r.t. for 15 min. To this mixture was added paraform-
aldehyde (3 g, 100 mmol) and the reaction mixture was refluxed for
1 h. HOAc was distilled off slowly over 15–20 min at 70–75 °C bath
temperature and the oily residue was further heated with stirring for
30 min at same bath temperature. After allowing the reaction mix-
ture to reach r.t., the residue was redissolved in HOAc (75 mL).
Ph3P (5.24 g, 20 mmol) and paraformaldehyde (3 g, 100 mmol)
were added to the reaction mixture and it was refluxed for 1 h. The
HOAc was distilled off in vacuo at 50–60 °C to obtain a thick oily
residue. Column chromatographic purification of the residue (silica
gel; PE–EtOAc, 9:1) gave pure 7: 2.92 g (68% yield).
(11) Kreiser, W.; Janitschke, L.; Ernst, V. L.; Sheldrick, W. S.
Chem. Ber. 1979, 112, 397.
(12) Baumann, M.; Kvita, V.; Roth, M.; Waterhouse, J. S. Swiss
Patent 598 253, 1978; Chem. Abstr. 1978, 89, 109071n.
(13) Boehner, B.; Baumann, M. Ger. Offen, 2 735 841, 1978;
Chem. Abstr. 1978, 88, 152415u.
(14) Ciba-Geigy, A.-G. Fr. Demande 2 400 013, 1979; Chem.
Abstr. 1980, 92, 163836r.
(15) Pichler, H.; Obenaus, F.; Franz, G. Erdoel, Kohle, Erdgas,
Petrochem. 1967, 20, 188.
(16) Kunichika, S.; Oka, S.; Tanaka, K. Bull. Inst. Chem. Res.
Kyoto Univ. 1966, 44, 221.
(17) (a) Shriner, R. L.; Ford, S. G.; Roll, L. J. Org. Synth. Coll.
Vol. 2; Wiley: Chichester, 1943, 140. (b) Shriner, R. L.;
Ford, S. G.; Roll, L. J. Org. Synth. Coll. Vol. 2; Wiley:
Chichester, 1943, 368.
(18) (a) Baumann, M. E.; Bosshard, H.; Breitenstein, W.; Rist, G.
Helv. Chim. Acta 1986, 69, 396. (b) Baumann, M. E.;
Bosshard, H.; Breitenstein, W.; Rihs, G.; Winkler, T. Helv.
Chim. Acta 1984, 67, 1897. (c) Baumann, M. E.; Bosshard,
H. Helv. Chim. Acta 1978, 61, 2751; and references cited
therein.
Dimethylmaleic Anhydride (8)
To the solution of imide (7, 9.30 g) in MeOH (100 mL) was added
a solution of KOH (12.1 g) in H2O (25 mL) and the reaction mixture
was refluxed for 2 h with stirring. The reaction mixture was concen-
trated in vacuo, the obtained residue was acidified with dilute aq
HCl and extracted with EtOAc (3 50 mL). The organic layer was
washed with H2O (30 mL), brine (30 mL) and dried (Na2SO4). Con-
centration of organic layer in vacuo gave 8: 5.26 g (97% yield); mp
94–96 °C.
(19) Pichler, H.; El, D.; Amin, Z. Ger. Offen. 2 206 713, 1973;
Chem. Abstr. 1973, 79, 125875b.
(20) Herrera, A.; Hoberg, H. Synthesis 1981, 831; and references
cited therein.
(21) Janitschke, L.; Kreiser, W. Synthesis 1976, 314; and
references cited therein.
IR (CHCl3): 1748 cm–1.
1H NMR (CDCl3, 200 MHz): = 2.08 (s, 6 H).
MS: m/z (%) = 126 (67), 82 (99), 67 (5), 54 (22).
(22) Hedaya, E.; Theodoropulos, S. Tetrahedron 1968, 24, 2241.
Synthesis 2002, No. 7, 865–868 ISSN 0039-7881 © Thieme Stuttgart · New York