2.3- Dimethylmaleic anhydride

Maleic anhydride is decomposed in the Hquid phase by various nitrogen bases. Treatment of maleic anhydride in refluxing acetic acid with 2-anainopyridine [504-29-0] gives, after work-up in 4 at 100°C, the decarboxylative dimeri2ation product, 2,3-dimethylmaleic anhydride [766-39-2]... 

Benzo[c]furan, generated in situ in boiling xylene in the presence of dimethylmaleic anhydride, gives mainly the exo adduct furan itself fails to react with this dienophile (Scheme 53) (82JOC4011. l,3-Diphenylbenzo[c]furan is also a reactive diene but the corresponding 1,3-dimesityl derivative is inert to several dienophiles, even under forcing conditions (82CC766). 

The photochemically induced [2 + 2] cycloaddition of selenophene with dimethylmaleic anhydride gives a 1 1 adduct (140), but attempts to form an oxetane by photoreaction with benzophenone failed (80JHC1151). 

Dimethylmaleic anhydride [766-39-2] M 126.1, m 96 , b 225 /760mm. Distd from benzene/ligroin and sublimed in a vacuum. 

Cyclopentadiene adds to dimethylmaleic anhydride to produce cyclobutane dimer (84) and two products from l,4-cycloaddition<97) ... 

Endo product (86) is thought to result from thermal addition and is probably not a photoproduct. Cyclohexadiene yields cyclobutanes (87)—(89) and 1,4-cycloaddition product (90) with dimethylmaleic anhydride(87> ... 

Photocycloadditions of maleic anhydride and dimethylmaleic anhydride to various other substituted cyclohexadienes and to cycloheptatriene have also been reported/58,97 98 ... 

During work-up after ozonolysis of the lactone to give dimethylmaleic anhydride, removal of excess ozone by a stream of oxygen leads to the precipitation of peroxidic material at the concentration used in the preparation. 

The first successful attempt to prepare bicyclic indolizinedione derivatives 210 was achieved by the reaction of dimethylmaleic anhydride with pyrrolylmagnesium bromide followed by the cyclization of the intermediate acid. The corresponding unsubstituted desmethyl compound cannot be prepared this way [90JCS(P1) 1463]. 

Acetone-sensitized [2+2]-photocycloaddition of 2(3//)-oxazolones 247a to maleic anhydride and dimethylmaleic anhydride gives the corresponding anti-cyclobutane cycloadducts 253 as the major products. Similar photoreaction of 2(37/)-oxazolones with 1,6-anhydro-4-(9-benzyl-2,3-dideoxy- 3-D-e 7t/ira-2-hex-enopyranose 254 results in the exclusive formation of the anh-cyclobutane-type adduct 255 (Fig. 5.61). ... 

Other five-membered heterocyclic enones used in [2 + 2] photocycloadditions are 1//-pyrrole-2,3-diones86-88 and derivatives of maleic anhydride. Some cycloadducts of dimethylmaleic anhydride and unsaturated acid esters have been used as monomers for condensation polymers.89... 

These investigators found that the normal acids occurred in much greater abundance than the branched acids. The cyclic acids isolated by Lochte and coworkers (31) include cyclopentanecarboxylic acid, 2-methylcyclopentanecarboxylic acid, 3-methylcyclopentane-carboxylic acid, cyclopentaneacetic acid, 3-methylcyclopentaneacetic acid, 2,3-dimethyl-cyclopentaneacetic acid, 1,2,2-trimethylcyclopentanecarboxylic acid, cyclohexanecarbox-ylic acid, p-methylcyclohexanecarboxylic acid, and the cis and trans forms of 2,2,6-tri-methylcyclohexanecarboxylic acid. In addition, Lochte and coworkers (31) isolated dimethylmaleic anhydride, which has also been isolated by Nenitzescu and coworkers (42). 

Diels-Alder route to cantharidin. Use of high pressure to facilitate. Diels-Alder reactions has led to a simple synthesis of cantharidin.1 The obvious dienophile component, dimethylmaleic anhydride, is unreactive to furane even under high pressure, but 2,5-dihydrothiophene-3,4-dicarboxylic anhydride (l)2 reacts with furane at 25° under 15 kbar of pressure to give the exo-adduct (2) and the endo-isomer as a 85 15 mixture. The major adduct is converted into cantharidin (3) by reduction and desulfurization over Raney nickel in 63% overall yield. 

In view of the inherent properties of the system, many attempts have been made to extend the shade range commercially but with little success. An example is the purple nickel chelate (65) derived from dimethylmaleic anhydride (B-71MI11207). 

Thermally unstable azetidines may be obtained by irradiation of furan in the presence of oxazolinones or 3-ethoxyisoindolone by [7r2s+ .2s] cycloaddition (Scheme 90) (75JA7298). Benzophenone photosensitized [ 2S+W2S] cycloaddition of furan to dimethylmaleic anhydride yields an adduct (34%). This reaction has been extended to 2,5-dimethylfuran and other maleic anhydrides and maleimides (76CA(84)120785). 

Triplet sensitized addition of several unsaturated compounds with thiophenes has been carried out. Citraconic and 2,3-dimethylmaleic anhydrides add thus to thiophene, 2-methyl-, 3-methyl- and 2,5-dimethyl-thiophenes (73JCS(P1)2322, 63CB498). The structure and stereochemistry of the products have been confirmed by application of NOE. With 2-methylthiophene, addition occurred at the unsubstituted double bond whereas with 3-methylthiophene, addition took place on the substituted double bond (Scheme 83). Benzo[6]thiophene also adds to the above anhydrides under triplet sensitization. With citraconic anhydride, there is no regiospecificity, both isomers being formed. 

The photochemically induced reaction of selenophene and dimethylmaleic anhydride gives mainly the [2+2] cycloadduct (79), but attempts to form an oxetane by photoreaction with benzophenone failed (80JHC1151). Photoirradiated in the presence of benzophenone, benzo[6 ]selenophene and some of its derivatives form [2+2] cycloadducts with dichloroethylene. Photoreaction with dimethyl acetylenedicarboxylate gives addition products which lose selenium to yield naphthalene derivatives (77T2225). 

Cyclopentenones. A recent synthesis of (+)-albene (5), a tricyclic natural product, from the Diels-Alder adduct (1) of cyclopentadiene and 2,3-dimethylmaleic anhydride required transformation of a succinic anhydride group to a cyclopehtenone (4). This was accomplished via a protected keto aldehyde 3 in four steps as formulated in 51% overall yield.1... 

Cantharidin (24) [31] represents the simplest known inhibitor of the ser-ine/threonine protein phosphatases 1 and 2A, and can be isolated from dried beetles (Cantharis vesycatoria). The simplest synthesis of 24 from furan and dimethylmaleic anhydride met with failure, even at pressures as high as 6.0 GPa either at rt or at temperatures of up to 350 °C, presumably due to the thermodynamic instability of the adduct at normal pressure, e.g., when pressure is released [32], However, if this reaction could be carried out in the presence of Pd/C and H2,24 might be obtained in one step. Nevertheless, high-pressure cycloaddition turned out to be very useful for the synthesis of cantharidin and its derivatives [31-33]. For instance, ( )-palasonin was synthesized from furan and citraconic anhydride (21) at 0.8 GPa for 138 h, followed by hydrogenation over Pd/C. Neither high temperatures nor... 

Substituted maleic anhydrides have been directly exdted, but sensitization may also be used. In some cases the first method is better, and in some cases the second. In an approach to merrilactone A, which is closely related to the earlier-mentioned synthesis (Scheme 6.30), 2,3-dimethylmaleic anhydride was employed as a starting material in a sensitized [2 + 2]-photocydoaddition to 1,2-dichlorethene [114]. The reaction of tetrahydrophthalic anhydride (120) with alkenols and alkynols was conducted by direct irradiation in a Pyrex vessel. As an example, the reaction with allyl alcohol is depicted. The exo-product 121 was the preferred product with the endo-product cydizing spontaneously to lactone 122 (Scheme 6.43) [115]. Other alkenols reacted similarly. 

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