Maleimides succinimides

Less intensively investigated than phthalimides was the photochemistry of maleimides, succinimides, and glutarimides. 

The reaction of sulfenyl chlorides with imides, e.g. maleimide, succinimide or phthalimide (66), provides a useful route for the preparation of disulfides (67) (Scheme 40) (see p. 57). The intermediate sulfenylimide (68) is quite stable but reacts with a thiol with expulsion of the imide moiety, which is a good leaving... 

The addition of the phthalimido anion to triesters of 2-phosphonopropenoic acid at room temperature gives an initial adduct, which is unexpectedly inert to benzaldehyde reaction but which adds to a second molecule of the phosphonic diester to form a second carbanion the latter undergoes an intramolecular WEH condensation to give the heterocyclic system 371 indolizine and quinolizine phosphonic diesters have been similarly obtained from maleimide, succinimide and glutarimide anions ". The ability of piperidine to add to the compounds 372 decreases in the order R R = (BuO)H (exothermic reaction) > (BuO)2 > (BuO)Me > Bu2 (the last requires heat) ". Ethenylphosphonic diamides (372 R = r2 = NR2) are unreactive to nucleophiles (by virtue of reduced electrophilic character at phosphorus and thus reduced electron attraction from the carbon-carbon double bond) but are reactive to electrophilic reagents. ... 

V-Alkyl or A/-aryl succinimides can be prepared from the corresponding amines (107) or from succinic anhydride, ammonia, and the corresponding alcohol (108). Succinimides are also obtained by vapor-phase hydrogenation of the corresponding maleimides ia the presence of a catalyst (109). 

The procedure described here for the preparation of succinimide silver salt is a modification of one reported for the formation of the silver derivative of maleimide. The alkylation step is modeled after the procedure of Comstock and Wheeler/ who prepared 2-ethoxypyrrolin-5-one in unspecified 3deld, and is an improvement over a later procedure developed in the laboratories of the submitters/ The general scheme has been successfully applied to the preparation of a variety of 2-ethoxypyrrolin-5-ones (Table 1) as well as 6-ethoxy- and 6-propoxy-4,5-dihydro-2(3H)-pyridone from the corresponding five- and six-membered cyclic imides/... 

Similarly, dialkylated succinimide (82) was obtained in the electrolysis of acid (80) with maleimide (81) (Scheme 29) [107]. 

If a free amino group forms a portion of the protein that is essential for activity (e.g., the antigen-combining site for antibody), biotinylation with the succinimide ester will lower or destroy the activity of the protein, and other methods of labeling should be tried. Biotin hydrazide has been used to modify the carbohydrate moieties of antibodies (10,11). Other alternatives are the thiol-reactive biotin maleimide (12) or biotin iodoacetamide (13). 

Scheme 6.71 Succinimide-containing substituted thiochromanes obtained from the 12-catalyzed enantio- and diastereoselective domino Michael-aldol reaction between 2-mercaptobenzaldehydes and maleimides.

In 2007, Wang and co-workers published a protocol for an enantio- and diastereoselective domino Michael-aldol reaction using electron-rich and electron-deficient 2-mercaptobenzaldehydes and maleimides as substrates [223]. The conversion was described to proceed smoothly in the presence of bifunctional catalyst 12 (lmol% loading) in xylenes at 0°C reaction temperature producing the desired chiral succinimide-containing substituted thiochromanes 1-5 in high yields (83-96%), in synthetically useful ee values (74—94%), and diastereoselectivities (up to dr 20 1) in 7h reaction time (Scheme 6.71). 

A variety of routes for incorporation of the succinimide group into a polymer backbone are provided by the use of bis(maleimide) monomers (8 Scheme 5). Examples include Michael addition of diamines or dithiols (or H2S) to produce poly(imides) (9) (B-80MI11101), and photopolymerization (via the triplet state) to prepare cyclopolymers (10) (73PAC213) having molecular weights of about 30 000. 

Maleimido groups are introduced into AChE by reaction of their primary amino groups with the jV-hydroxy-succinimide moiety of SMCC m neutral medium. This reaction is very similar to that used for incorporation of biotin molecules into proteins Prior to this reaction, the enzyme is treated with / /-ethyl maleimide in order to block any thiol groups. Finally, SMCC-AChE is purified by molecular sieve chromatography on a Biogel A 1.5 m column. 

Catalytic hydrogenation of porphyrazines or their Mg complexes with palladium black gives tetrahydrogenated compounds which are oxidized back to the starting materials by a stoichiometric amount of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ).2 The royal blue products are degraded to cw-succinimide and maleimide, and considered to be the tetraaza analogues of either bacterio-chlorins or isobacteriochlorins. Photochemical reduction of monoazaporphyrins is reported to occur at the meso positions. 

N-(y-Maleimidobutyryloxy)succinimide ester (GMBS) is a heterobifunctional cross-linking agent that contains an NHS ester on one end and a maleimide group on the other (Fujiwara etal., 1988) (Pierce). Its internal cross-bridge contains a linear 4-car-... 

Figure 5 Covalent coupling of cyclic peptide moieties to human serum albumin (HSA). The depicted cyclic peptide, C SRNLIDC, in which C denotes the cyclizing cysteine residues, mimics the receptor binding site of PDGF-BB. First, a sulfhydryl group is introduced to the cyclic peptide by a reaction with succinimide-acetyl thioacetate (SATA). The primary amino groups of lysine in HSA are derivitized with maleimide-hexoyl-At-hydroxysuccinimide ester (MHS). Subsequently, the cyclic peptide is coupled to HSA. In this latter reaction, hydroxyl amine is used to remove the protecting acetate group from the sulfhydryl group of the cyclic peptide.

All of the above dyes can be purchased in N-succinimide activated form and used for labeling of amino groups (see below). The choice of fluor-ophores are more limited for labeling of thiol groups with maleimide derivatives of dyes, and especially for full synthesis of oligos using dye-labeled phosphoramidites. 

Relatively few examples have been reported in which the chromophoric group was an aryl ketone (13a) - many more PET-induced cydizations with phthali-mides (13b) are known [8]. (Sometimes other imides, for example succinimides and maleimides have been used.)... 

During the solid-state polymerization the maleimide disappears as the substituted succinimide forms as shown in Fig. 7. An aromatic absorption at 1515 cm-1 similar for both the maleimide and crosslinked succinimide network was used as an internal standard. The disappearance of the absorption band located at 1150 cm-1 (v C-N-C) plotted as a function of the increase of the corre-... 

However, FTIR spectroscopy is not accurate enough to differentiate between the succinimide formation either by a nucleophilic addition of an aromatic diamine on the maleimide or by radical crosslinking. NMR spectroscopy offers a possibility to analyze the two different mechanisms and Fig. 8 shows the 13C chemical shifts of different carbon atoms as a function of the product structures [17]. 

There were relatively few examples reported, in which the chromo-phoric group was an aryl ketone (Ilia) whereas much more PET induced cyclizations with phthalimides (Illb) are known, sometimes other imides, such as succinimides and maleimides were also used. Phthalimides differ from aryl ketones in some respects despite their apparently similar photophysical properties. On one hand, their reduction potential is remarkably lower in comparison with aryl ketones [13]. On the other hand, the radical anion derived from phthalimides is clearly more stable than the corresponding species from aryl ketones [15]. Both facts increase the thermodynamic driving force of a PET and facilitates applications that are unknown from aryl ketones. In this context, one of the most successful approaches is a PET-induced decarboxylation-cyclization route, developed by Griesbeck [13]. The details of this interesting method will be discussed in Sec. 3.4.6. 

Compounds 43 and 44 are not intermediates in the formation of pyrrole blacks. During oxidation with hydrogen peroxide in pyridine, small quantities of succinimide and maleimide were identified by paper chromatography.4 4... 

Succinimides and maleimides are accessible via processes analogous to those described for the corresponding anhydrides (see Section 9.4.3.3). Reactions of (COD)2Ni° with either alkenes or alkynes and isocyanates (i.e. heterocumulene analogs of CO2) give azametallacycles that upon carbonylation yield cyclic imides. With alkenes high yields of metallacycles are formed m both simple isocyanates as well as a,(o-diisocyanates. Carbonylation yields are variable, however (Scheme 18). Alkynes give lower metallacycle yields but high yields of die final imide (Scheme 19). ... 

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