Maleimides Michael reactions

Bismaleimides - Bismaleimides resins were first introduced into the market in the early 1970 s. As with other resin systems, there are many variations of bismaleimides. The Kermid and Kinel bismaleimide products as marketed in the U. S. by Rhodia are representative examples. Bismaleimide chemistry is represented in Eq. 3 where curing can be accomplished thermally through the unsaturation in the maleimide or by way of the Michael Reaction where an appropriate curing agent such as aromatic diamine adds across the activated double bond. In most instances, a combination of curing thermally through the double bond and via an aromatic diamine is used in actual practice. Bismaleimides are frequently formulated... 

Tan and co-workers reported the Michael reactions of di-thiomalonates and P-keto-thioesters to a range of acceptors, including maleimides, cyclic enones, furanones and acyclic dioxobutenes [129]. Unlike dimethyl malonate, additions with acidic thioesters proceeded in higher yields, and overall better enantioselectivities (Scheme 74). 

The ability of the maleimide unit to switch off emission is also exemplified by 86, due to Verhoeven s coworkers [161] at the University of Amsterdam and Akzo Nobel in The Netherlands. Again the Michael reaction of the maleimide with thiols produces nicely emissive material. Solvent-sensitive emission, characteristic of these donor-acceptor systems with strongly coupling bridges, is a special feature of 86 after thiolation. An added interest of 86 stems from the occurrence of PET to the maleimide unit from the through-bond charge-transfer excited state [162], an unusual combination of photophenomena. 

Figure 5. Bioorthogonal reactions on sugars, A. Ketones react with hydrazides to give hydrazones. B. Thiols undergo Michael Reaction with maleimides. C, Azides undergo Staudinger ligation with phosphines or D. strain-promoted or copper catalyzed [3 2] cycloaddition with all nes. E. Alkynes undergo copper-catalyzed [3- 2] cycloaddition with azides.

Scheme 2.31 Enantioselective Michael reaction using maleimides and y-keto-a,P-unsaturated esters as Michael acceptors.

The reaction has heen expanded to an asymmetric thio-Michael reaction by the addition of aiylmethyl mercaptans to cyclohex-2-enone in the presence of 10 mol% of triphenylmethyl-L-cysteine (9 examples, 44-86%, ee 8-58%). Maleimides undergo Michael addition with a,a-disubstituted aldehydes (Scheme 12.10). Several catalytic systems have been tested to promote the reaction, including a- or p-amino acids, potassium salts of amino acids... 

Fluorous thiourea organocatalyst (103) promotes Michael reaction of aldehydes with maleimides in high yield, and ee sometimes >99%. Catalyst (103), easily prepared 0 in one step from readily available materials, can be recovered by filtration and is reusable. 

In addition, more sophisticated albumin polycation architectures have been designed. Serum albumins offer a single reactive thiol group that is accessible for site-directed chemistry, e.g., Michael reactions with a maleimide functionality that can react exclusively at this position. Two cBSA-147 molecules have been interconnected by a poly(ethylene oxide) (PEO) polymer linker and the successful formation of the cBSA dimers has been visualized by transmission electron microscopy (TEM). These cBS A-dimers revealed efficient cellular uptake as well as transfection of pDNA-GFP. 

An enantioselective Michael reaction of aldehydes and maleimides gives up to 99% yield and ee, using a cooperative catalysis by a chiral primary amine and triphenylphosphine. Evidence for a supramolecular assembly of the catalysts is presented, including UV/visible, fluorescence, CD and NMR spectroscopy, and ESI-MS. 

The MW-assisted phospha-Michael reaction was then extended to the addition of dialkyl phosphites, a phenyl-H-phosphinate and diphenylphosphine oxide to maleic derivatives, N-substituted maleimide, and maleic acid anhydride giving rise to >P(0)-substituted succinic derivatives (38 and 39) (Scheme 13) [58]. 

A fluorous thiourea organocatalyst 28 was conveniently prepared from a chiral diamine (Scheme 7.29) [45]. The fluorous thiourea 28 catalyzed the Michael reaction of maleimides and aldehydes with high yield and enantioselectivity. The catalyst 28 could be recycled by simple filtration and reused without significant loss of catalytic activity and enantioselectivity, while the catalyst recovery yield dropped dramatically after three cycles. 

The Michael addition of nucleophiles to the carbon—carbon double bond of maleimide has been exploited ia the synthesis of a variety of linear polymers through reaction of bismaleimide with bisthiols (39). This method has been used to synthesize ethynyl-terminated imidothioether from the reaction of 4,4 -dimercaptodiphenyl ether [17527-79-6] and A/-(3-ethynylphenyl)maleimide (40). The chemical stmcture of this Michael addition imide thermoset is as follows ... 

The Michael addition reaction of amines and thiols with bismaleimides or functionalized monomaleimides is a versatile tool ia the synthesis of chain-extended maleimide-terroinated prepolymers. These prepolymers generally are soluble ia organic solvents from which they can be processed to prepreg and molded to high quaUty, void-free laminates. 

Maleimides have three principal reaction pathways. These are radical addition to vinyl compounds the Michael addition with compounds having active hydrogens and the Diels-Alder reaction with dienes (Fig. 3). Any of the three can be tools for forming thermosetting adhesives. 

A typical maleimide resin is synthesized by the Michael addition of MDA and BMI (Fig. 4). If the stoichiometrically equal amounts of MDA and BMI are added into the reaction solvent under controlled temperature, linear, high molecular weight polyaminoimide (PAI) results. To obtain crosslinkable oligomer (pre-polymer) with maleimide end groups, a calculated 1.1-1.8 times an excess... 

Recently, Tan reported related bicyclic guanidine 20 as a chiral Br0nsted base to promote the highly enantioselective Diels-Alder reaction of various anthrones and maleimides (Scheme 5.41) [75]. Interestingly, use of dithranol led to the exclusive formation of the enantio-enriched Michael adducts. 

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). 

The maleimide group can undergo a variety of chemical reactions. The reactivity of the double bond is a consequence of the electron withdrawing nature of the two adjacent carbonyl groups which create a very electron-deficient double bond, and therefore is susceptible to homo- and copolymerizations. Such polymerizations may be induced by free radicals or anions. Nucleophiles such as primary and secondary amines, phenates, thiophenates, carboxylates, etc. may react via the classical Michael addition mechanism. The maleimide group furthermore is a very reactive dienophile and can therefore be employed in a variety of Diels Alder reactions. Bisdienes such as divinylbenzene, bis(vinylbenzyl) compounds, bis(propenylphenoxy) compounds and bis(benzocyclobutenes) are very attractive Diels Alder comonomers and therefore some are used as constituents for BMI resin formulations. An important chemical reaction of the maleimide group is the ENE reaction with allylphenyl compounds. The most attractive comonomer of this family is DABA particularly when tough bismaleimide resins are desired. 

Another base catalyzed side reaction is the formation of Michael adducts between the maleimide and the acetic acid present in the reaction mixture. In general, both the acetanilides and the Michael adducts are favored when high catalyst concentrations and high temperatures are used for the synthesis. 

The Michael addition reaction of dimercaptodiphenylether with N-(3-ethynyl phenyl) maleimide allowed the synthesis of ethynyl-terminated imido-thioether as shown in Fig. 50 (139). This acetylene terminated imidothioether was blended with acetylene terminated polyarylene ether oligomers of different molecular weights and tested as composite resins (140). Blends of functionalized thermoplastics such as the acetylene terminated polyarylene ethers with brittle high-Tg imide resins are finding increased attention for tough high-Tg composites. 

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