3.4- Disubstituted maleic anhydride

Starting from 3,4-disubstituted maleic anhydride, Klopfleisch and coworkers synthesized the bilirubin oxidation end-product BOX A and isomers in four or six steps (20130L4608). Within this synthesis they transformed 5-alkylidene-furan-2-ones to the corresponding substituted 3-pyrrolin-2-ones using ammonium acetate and glacial acetic acid. Seidel and coworkers employed a similar approach to BOX B analogs (2014TL6526). 

The reaction of diaryl compounds 2-974 with 3 equiv. of DB U at r. t. results initially in an intramolecular aldol condensation to give 2-975 this is followed by an oxidation to give the 3,4-diaryl disubstituted maleic anhydride or maleimide derivatives 2-976 when the reaction is conducted under atmospheric oxygen (Scheme 2.219). 

II. The isolation of disubstituted maleic anhydrides from the strong acid fraction RDR, 1963, No. 2, January 14, see www.ijrtdocs.com 500961031 -1050. 

If disubstituted maleic anhydride is used in this reaction, even with boiling in toluene solution for 46 h, the process does not go past the stage of formation of the corresponding derivative of succinic acid-3-[(3-methylquinoxalin-2-yl)methyl]-3,4-diphenyldihydrofuran-2,5-dione 55 (Fig. 3.4), which is isolated with a yield of 90 % (Cheeseman and Tuck 1965a). 

If the reaction of the 2,3-disubstituted-l, 3-butadienes is with a symmetric dienophile, such as maleic anhydride, the 2 and 3 positions in the diene are equivalent, and therefore... 

N-silylated imines 509 react with the Li salts of tosylmethylisonitriles to give 4,5-disubstituted imidazoles in moderate yields [93]. Acetylation of N-trimethylsilyl imines 509 with acetyl chloride and triethylamine affords 72-80% of the aza-dienes 510 these undergo readily Diels-Alder reactions, e.g. with maleic anhydride at 24 °C to give 511 [94] or with dimethyl acetylenedicarboxylate to give dimethyl pyridine-3,4-dicarboxylates [94] (Scheme 5.29). 

With some exceptions, 1,2-disubstituted ethylenes containing substituents larger than fluorine such as maleic anhydride, stilbene, and 1,2-dichloroethylene exhibit little or no tendency... 

Cycloaddition of the 2,5-disubstituted sulfolenes (559) with diazomethane takes place on the less hindered face, resulting in cis -fused compounds (560) in which the substituents occupy the exo position. Irradiation of these gives the cyclopropanes (561) (70JA6918). Photochemical [2 + 2] cycloaddition of sulfolene with maleic anhydride and maleimides is known (Scheme 216) (77AHC(2l)253). 

Alder s endo rule applies not only to cyclic dienes like cyclopentadiene and to disubstituted dienophiles like maleic anhydride, but also to open chain dienes and to mo no-substituted dienophiles diphenylbutadiene and acrylic acid, for example, react by way of an endo transition structure 2.113 to give largely (9 1) the adduct 2,114 with all the substituents on the cyclohexene ring cis, and equilibration again leads to the minor isomer 2.115 with the carboxyl group trans to the two phenyl groups. 

The photolysis of Barton esters (N-hydroxy-2-thiopyridone esters, 43) proved to be an efficient method for generating carbon-centered radicals that are exploited for the regioselective alkylation of electron-deficient olefins a thiopyridyl unit is likewise incorporated into the end products. In a recent application, Barton esters were found useful in the synthesis of natural and unnatural disubstituted maleimides or maleic anhydrides by way of two consecutive radical addition steps, as described in Scheme 3.27 [72]. 

Hexaphenyl Monosubstituted eihylenes, disubstituted butadienes, maleic anhydride, maleimide, dehydrobenzene 320, 321... 

One of the most common and versatile methods for the S3mthesis of polyfunctional pyridazines consists in the formation of the diazine ring from maleic anhydride or its mono- and disubstituted analogs and an unsubstituted, mono-, or disubstituted hydrazine. Pyridazinones of the types 21 and 22 are obtained in good yields. 

Acyclic ( -pentadienyl)Fp complexes also behave as Diels-Alder dienes in some cases, although two other reaction pathways compete. With TCNE and maleic anhydride, (17 R = H, Me) undergoes cycloaddition in moderate yields. Highly electron-deficient alkynes, on the other hand, undergo Fe bond insertion reactions reminiscent of SO2 reactions with ( -allyl)Fp complexes, to give (30). Finally, when the pentadiene is disubstituted at C-5, the Diels-Alder route is effectively blocked, and [3 + 2] cycloadditions result with TCNE at the 2,3-double bond. ... 

Some unusual zwitterionic pyrazines have been prepared by dehydrogenation of 1,4-disubstituted piperazine-2,6-diones. Honzl et al. (476a) prepared theanhydro-2,6-dihydroxy-l, 4-diphenyl-3,5-bis(phenylthio)pyrazinium dihydroxide [s/c] (92) (which yields adducts by dipolar cycloaddition of maleic anhydride or formaldehyde) by the reaction of 1,4-diphenylpiperazine-2,6-dione with benzenesulfonyl chloride in pyridine. Tanaka et al. (476b), from I,4-diphenylpiperazine-2,6-dione with benzoyl chloride, and tosyl chloride in pyridine at reflux, obtained the anhydro - 3 - benzoyl - 2,6 -dihydroxy -1,4 -diphenyl - 5 - (p - toly lthio)pyrazinium dihydroxide [src] (93), together with some of the S-p-tolyl analogue of (92). 

Diels-Alder reactions of l-methyl-2-(lH)-pyridinone (66) with maleic anhydride [71,72,73] and fumaronitrile [74] produced 2,6-disubstituted lactam-ISQs. Reaction of 66 with methyl acrylate and acrylonitrile yielded monosubstituted ISQ derivatives (67-68) in 23-30% overall yield (Scheme 5) [75]. 

Additions to compounds with activated double or triple bonds are known. Compound 406 (R = Me) gives 427 with acrylonitrile(405 does not react ), and 401 reacts with diethyl azodicarboxylate and maleic anhydride to give 428 and 429, respectively. The 2,6-dimethyl derivative of 396 undergoes addition to dimethyl acetylenedicarboxyl-ate at C-5 (position a. Scheme 18), but tetracyanoethylene gives both C-5 and C-7 (a and b) products, the latter predominating. Reid had earlier reported that 396 reacts with bulky electrophiles to give mixtures of products and disubstituted derivatives. 

The rates of radical-monomer reactions are also dependent on considerations of steric effects. It is observed that most common 1,1-disubstituted monomers — for example, isobutylene, methyl methacrylate and methacrylo-nitrile—react quite readily in both homo- and copolymerizations. On the other hand, 1,2-disubstituted vinyl monomers exhibit a reluctance to ho-mopolymerize, but they do, however, add quite readily to monosubstituted, and perhaps 1,1-disubstituted monomers. A well-known example is styrene (Ml) and maleic anhydride (M2), which copolymerize with r — 0.01 and T2 = 0 at 60°C, forming a 50/50 alternating copolymer over a wide range of monomer feed compositions. This behavior seems to be a consequence of steric hindrance. Calculation of A i2 values for the reactions of various chloroethylenes with radicals of monosubstituted monomers such as styrene, acrylonitrile, and vinyl acetate shows that the effect of a second substituent on monomer reactivity is approximately additive when both substituents are in the 1- or cr-position, but a second substituent when in the 2- or /3-position of the monomer results in a decrease in reactivity due to steric hindrance between it and the polymer radical to which it is adding. 

Reaction of 2,3-dimethylquinoxaline with monosubstituted maleic anhydrides (49) gives only one of the two possible isomers. The products formed are of formula 51. This implies that the reaction proceeds through an intermediate 50 rather than the isomeric 52. With disubstituted maleic... 

Unlike monosubstituted and 1,1-disubstituted ethylenes, 1,2-disubstituted ethylenes, as a whole, cannot undergo homopolymerization and form high molecular weight polymers (22). Maleic anhydride (MAH) and its mono- and diesters make an example of such compounds. 

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